PMID- 9008838
TI  - Cholesterol screening in childhood: results of a 9-year follow-up study in Swiss
      and Italian children in Switzerland.
AB  - Mass screening for blood cholesterol as part of routine preventive health care of
      children continues to be discussed in several countries. Results of longitudinal
      studies underline the importance of the predictive value of cholesterol levels
      assessed during childhood. Some countries have changed their recommendations
      during the past years to blood cholesterol screening for obese children only or
      for children of high risk families. In the Kindergarten-study Basel, a follow-up
      study on somatic, psychic and social development of Swiss and immigrant
      schoolchildren, cardiovascular risk factors were assessed at the ages of 5, 10
      and 14 years. The age-specific levels of total and LDL-cholesterol found in our
      study were slightly higher and HDL-cholesterol lower than, for example, those
      found in the Bogalusa Heart Study. For total cholesterol no significant tracking
      correlations over the 5 and 9 year periods were found. Tracking of LDL- and HDL
      cholesterol differed between nationalities and sexes. The total cholesterol/HDL
      cholesterol index tracked slightly better. Italian girls showed the best 9-year
      tracking for HDL-cholesterol (r = 0.56). The differences between this and other
      studies can only partially be explained by different sampling and laboratory
      methods. Individual changes in cholesterol levels between the ages of 5 and 14
      were marked. Sexual maturation was found to be of minor influence. Body mass
      index was the most consistent risk factor in our population. Changes of sex or
      growth hormone levels during puberty, but also changes of nutritional habits or
      physical activity might influence the individual cholesterol levels. Before
      recommendations on mass screening of cholesterol in children are made, the
      different longitudinal patterns of changes in cholesterol levels, and
      subpopulation-specific changes of nutritional habits and physical activity,
      should be discussed. The results of the Kindergarten study Basel suggest that
      attention should be paid to screening for obesity and to health education
      regarding nutrition and physical activity.

PMID- 9008839
TI  - Longitudinal epidemiological study of coronary heart disease in a rural
      population of Kheda district, Gujarat, India.
AB  - The present study was undertaken to determine the incidence and related risk
      factors for coronary heart diseases and hypertension in the rural population of
      Kheda district, Gujarat (India). The observations from the first five years of
      this ongoing project (May 1987-May 1992) are described in this paper. Out of an
      initial sample of 750 individuals in the age group 30-62 years, who were selected
      by stratified random sampling, 714 persons (males = 429; females = 285) were
      actually studied, after excluding those suffering from coronary heart diseases
      (CHD). Initially, all the included subjects were examined clinically and
      appropriate laboratory investigations were done. A detailed socio-economic
      history was also obtained. Subsequently all of them were followed up and biannual
      clinical and laboratory investigations were performed. Cases of CHD were
      diagnosed according to the recommendations of the New York Heart Association. The
      overall five-year incidence of CHD was 25.17 per thousand persons. The incidence
      in males was 3 times higher than in females. More males suffered from myocardial
      infarction (MI), while in the females the incidence of sudden death was higher
      (33.3%). The average yearly mortality rate due to CHD was 2.46 per thousand
      persons. CHD was significantly associated with increased blood pressure (both
      diastolic and systolic), smoking, and family history of heart disease, and was
      weakly associated with body weight (p = 0.06).

PMID- 9008840
TI  - Complete 1H and 13C resonance assignments of a 21-amino acid glycopeptide
      prepared from human serum transferrin.
AB  - A 21-amino acid glycopeptide (Gp21) was isolated and purified in multi-milligram
      yields from commercially available human serum transferrin (HSTF) by a
      combination of tryptic digestion, Con A affinity chromatography, and reverse
      phase HPLC. The peptide chain of Gp21 contains a single N-glycosylation site to
      which a diantennary oligosaccharide is attached. The amino acid sequence and the
      glycan primary structure of Gp21 have been verified by peptide sequencing,
      electrospray mass spectrometry, and one-dimensional 1H NMR spectroscopy.
      Different glycoforms were found for the glycan of Gp21 derived from two different
      batches of commercial HSTF. These glycoforms differ from one another in the
      number of NeuAc residues (ranging from 0 to 2) and/or the number of Gal residues
      (ranging from 1 to 2). As for the monogalacto species, in the two-dimensional
      nuclear Overhauser effect (NOE) spectrum of Gp21, interglycosidic NOEs were
      observed between Man4 in the alpha (1-->3) branch and the terminal GlcNAc beta (1
      ->2) residue. No interglycosidic NOE was observed between Man4' in the alpha (1-
      >6) branch and the terminal GlcNAc residue. These observations indicate that the
      terminal GlcNAc residue in the minor glycoforms of Gp21 is exclusively located in
      the alpha (1-->3) branch of the Gp21 glycan. The occurrence of such a
      carbohydrate structure in HSTF has not been reported before. The 1H and 13C NMR
      spectra of Gp21 have been completely assigned by two-dimensional homonuclear and
      heteronuclear spectroscopy. The close similarity of the 1H and 13C chemical shift
      values for the Gp21 glycan with the respective values for the peptide-free
      diantennary oligosaccharide (Wieruszeski et al., Glycoconjugate J., 6 (1989) 183
      194) indicates that the 1H and 13C chemical shifts of the diantennary
      oligosaccharide are not perturbed by the presence of the Gp21 peptide fragment.
      The complete 1H and 13C resonance assignments and the full characterization of
      the primary structure of Gp21 will permit us to study the conformation and
      dynamics of the N-linked diantennary oligosaccharides while covalently attached
      to a polypeptide fragment.

PMID- 9008841
TI  - Cyclolaminarinose. A new biologically active beta-(1-->3) cyclic glucan.
AB  - A unique glucan has been isolated from a recombinant strain of a Rhizobium
      meliloti TY7, a cyclic beta-(1-->2) glucan mutant carrying a locus specifying
      beta-(1-->3; 1-->6) glucan synthesis from Bradyrhizobium japonicum USDA110. This
      compound, which appears to have considerable hydrophobic affinity, was separated
      from a perchloric acid cell extract by adsorption to a C-18 silica column. Unlike
      those cyclic glucans previously isolated from Rhizobium meliloti or
      Bradyrhizobium japonicum, this molecule contains neither phosphoglycerol nor
      phosphocholine substituents, respectively. 2D NMR, FAB mass spectrometric
      analysis and high-performance anion exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD) confirmed that this glucan is a single, cyclic
      decasaccharide (cyclolaminarinose) in which one of the residues is substituted in
      its 6-position with beta-laminarabiose. This structural assignment was confirmed
      by mass spectral and NMR analyses of the product obtained from two consecutive
      Smith degradations. Unlike the complex 13C spectrum of the unoxidized material,
      the spectrum of this product consisted of only six resonances due to rapid time
      averaging of its symmetrical structure on the relatively slow NMR timescale.
      Synthesis of this newly described cyclic beta-glucan in the R. meliloti ndvB
      mutant restored the symbiotic and hypoosmotic adaptation characteristics of the
      R. meliloti wild type strain.

PMID- 9008842
TI  - Conformational studies of myo-inositol phosphates.
AB  - The discovery of the second messenger role of myo-inositol 1,4,5
      trisdihydrogenphosphate [Ins(1,4,5)P3] has triggered tremendous interest in
      investigating the structure, metabolism, and biological roles of inositol
      phosphates. Although the conformation of phytic acid [(myo-inositol
      hexakisdihydrogenphosphate), Ins P6] has been the subject of much study, the
      conformations of lower inositol phosphates such as inositol-pentakis-, tetrakis-,
      and tris-dihydrogenphosphates have not been investigated. We investigated, by 1H
      NMR spectroscopy, the conformations of inositol phosphates (Ins P5, Ins P4, Ins
      P3, Ins P2, and Ins P1) and monitored the influence of pH on conformational
      preferences. Ins P6 adopts the sterically stable 1ax/5eq (one phosphate in the
      axial position and five phosphates in the equatorial position) conformation in
      the pH range 0.5-9.0, and the sterically hindered 5ax/1eq (five phosphates in the
      axial position and one phosphate in the equatorial position) conformation above
      pH 9.5. At pH 9.5, both conformations are in dynamic equilibrium.
      Ins(1,2,3,4,6)P5 and Ins(1,2,3,5,6)P5 adopt the 1ax/5eq form in the pH range 1.0
      9.0; in the pH range 9.5-13.0, the 1ax/5eq and 5ax/1eq conformations are in
      dynamic equilibrium. In contrast to Ins P6 and Ins P5, all the lower inositol
      phosphates (Ins P4 to Ins P1) investigated adopt the 1ax/5eq conformation over
      the entire pH range, 1.0-13.0. Preference for the 5ax/1eq conformation by Ins P6
      and Ins P5 is probably due to decreased electrostatic repulsion between
      negatively charged vicinal equatorial phosphates in the 1ax/5eq conformation and
      stabilization of the sterically hindered 5ax/1eq conformation by hydrogen bonding
      and/or sodium counter-ions bonding between the syn-oriented phosphates. On the
      basis of conformations adopted by the inositol phosphates (Ins P6 to Ins P1) at
      different pH, we conclude that the presence of four or five equatorial phosphates
      on the inositol ring induces a change in the conformation from the sterically
      unhindered 1ax/5eq structure to the sterically hindered 5ax/1eq conformation, at
      high pH. This investigation illustrates that the conformational preferences of
      inositol phosphates at different pH is unique to the particular isomer and does
      not parallel the behaviour of phytic acid.

PMID- 9008843
TI  - Structural studies of the major glycolipid from Saccharopolyspora genus.
AB  - A major glycolipid was isolated from the well characterized Saccharopolyspora
      species, S. hirsuta, S. rectivirgula, S. erythraea and one not completely
      identified strain (Saccharopolyspora sp.). On the basis of sugar and methylation
      analysis, specific enzymatic and chemical degradations of the carbohydrate
      moiety, its FAB mass spectrometry and NMR spectroscopy characterizations, the
      carbohydrate part was shown to be the glycerol linked dimannoside alpha-D-Manp-(1
      ->3)-alpha-D-Manp-(1-->1/3)Gro. The internal mannose residue is esterified at C-6
      by one fatty acid residue, whereas another fatty acyl chain substitutes the
      primary methylene position of glycerol. The main fatty acyl residues are anteiso
      branched heptadecanoic acid and the iso-branched fatty acids iso-17:0, iso-16:0,
      and iso-18:0, with the former species being predominant. The major glycolipid has
      potential value for taxonomic and diagnostic purposes, especially in the specific
      diagnosis of farmer's lung disease.

PMID- 9008844
TI  - Full 1H NMR assignment and detailed O-acetylation patterns of capsular
      polysaccharides from Neisseria meningitidis used in vaccine production.
AB  - We report essentially complete 1H NMR assignments for the capsular
      polysaccharides from Neisseria meningitidis serotypes A, C, W-135, and Y. These
      polysaccharides are components of current polysaccharide vaccines against
      meningococcal infection and of the polysaccharide-protein conjugate vaccines
      under development. From these NMR data the pattern of O-acetylation was
      determined. O-Acetylation of the W-135 polysaccharide is reported for the first
      time. We also show that, for the Types C and W-135 polysaccharides a migration of
      O-acetyl groups occurs during storage in solution, and demonstrate that high
      field 1H NMR represents a simple and sensitive method to define the O-acetylation
      pattern of individual batches of these polysaccharides.

PMID- 9008845
TI  - N-trichloroethoxycarbonyl-glucosamine derivatives as glycosyl donors.
AB  - D-Glucosamine can be readily transformed into 1,3,4,6-tetra-O-acetyl-2-deoxy-2
      (2,2,2-trichloroethoxycarbonylamino+ ++) -D-glucopyranose (2). From this
      intermediate valuable glycosyl donors can be obtained; reaction with ethanethiol
      in the presence of boron trifluoride etherate afforded ethyl 3,4,6-tri-O-acetyl-2
      deoxy-1-thio-2-(2,2, 2-trichloroethoxycarbonylamino)-beta-D-glucopyranoside (4)
      which gave, upon N-acetylation, the N-acetyl-N-trichloroethoxycarbonyl derivative
      (5). Selective removal of the 1-O-acetyl group in 2 followed by treatment with
      trichloroacetonitrile in the presence of base afforded 3,4,6-tri-O-acetyl-2-deoxy
      2-(2,2,2-trichloroethoxycarbonylamino)- alpha -D-glucopyranosyl
      trichloroacetimidate (6). Reaction of 5 with five selectively protected
      glycosides as glycosyl acceptors in the presence of N
      iodosuccinimide/trifluoromethanesulfonic acid as the promoter system furnished
      the corresponding beta-glycosides in good yields, thus exhibiting the valuable
      glycosyl donor properties of 5. Reductive removal of the trichloroethoxycarbonyl
      (Teoc) group afforded the corresponding N-acetyl-protected saccharides in high
      yields. The imidate 6 reacted with three of the above acceptors in the presence
      of catalytic amounts of trimethylsilyl trifluoromethanesulfonate to give the beta
      linked disaccharides in even better yields. The direct replacement of the N-Teoc
      group by the N-acetyl group using zinc/acetic anhydride, via the free amines as
      transient intermediates, adds to the high efficiency and convenience of this
      methodology.

PMID- 9008846
TI  - Synthesis of alpha- and beta-linked tyvelose epitopes of the Trichinella spiralis
      glycan: 2-acetamido-2-deoxy-3-O-(3,6-dideoxy-D-arabino-hexopyranosyl)-beta -D
      galactopyranosides.
AB  - The anomeric configuration of tyvelose, 3,6-dideoxy-D-arabino-hexopyranose, in
      the recently discovered glycan epitopes of the parasite Trichinella spiralis has
      not been established. Two 2-(trimethylsilyl)ethyl disaccharide glycosides, alpha-
      and beta-Tyv-(1-->3)-beta-D-GalNAc (4 and 5), have been synthesized to provide
      model compounds that, together with the methyl 3,6-dideoxy-alpha- and beta-D
      arabino-hexopyranosides (2 and 3), aid the determination of the anomeric
      configuration of tyvelose residues in the parasite glycan, either indirectly by
      immunochemical inhibition data or directly by the technique of 1H NMR
      spectroscopy. Methyl 3,6-dideoxy-beta-D-arabino-hexopyranoside (3) was
      synthesized from methyl 2,3-anhydro-4,6-O-benzylidene-beta-D-mannopyranoside (9)
      by a method previously used for the alpha anomer 2. Benzylation of 2 provided a
      route to the glycosyl donor, 2,4-di-O-benzyl-3,6-dideoxy-alpha-D-arabino
      hexopyranosyl chloride (30), that reacted with the selectively protected 2
      acetamido-2-deoxy-D-galactopyranoside alcohol 18 in the presence of an insoluble
      silver zeolite catalyst to give the alpha- and beta-linked disaccharides 31 and
      32. Glycosylation of the related 2-acetamido-2-deoxy-D-galactopyranoside alcohol
      27 by 30 under similar conditions provided disaccharides 33 and 34 containing a
      tether. Deprotection of the saccharide and derivatization of the tether with 1,2
      diaminoethane provided amide derivatives 35 and 36 suitable for the preparation
      of neoglycoconjugate antigens. Complete 1H and 13C NMR chemical shifts of the
      deprotected disaccharides and monosaccharides are reported.

PMID- 9008847
TI  - Synthesis of a hexasaccharide acceptor corresponding to the reducing terminus of
      mycobacterial 3-O-methylmannose polysaccharide (MMP).
AB  - The title compound methyl O-(2,6-di-O-benzyl-3-O-methyl-alpha-D-mannopyranosyl)
      [(1-->4) -O-(2,6-di-O-benzyl-3-O-methyl-alpha-D-mannopyranosyl)]4-(1-->4) -2,6-di
      O-benzyl-3-O-methyl-alpha-D-mannopyranoside (2) was synthesized in a blockwise
      manner, employing trichloroacetimidate (11) and (20) as glycosyl donors. The
      strategy relies on the single-step preparation of the 3-O-methyl ethers (4) and
      (12) as starting materials. Since all intermediates contain one or more OCH3
      groups, they are easily identified by NMR spectroscopy using the methyl proton
      signals. Compound 2 corresponds to the reducing terminal hexasaccharide of
      mycobacterial 3-O-methyl-mannose polysaccharide (MNP). MMP has the unusual
      property of stimulating the fatty acid synthetase multienzyme complex. Compound 2
      can serve as a suitable glycosyl acceptor for the synthesis of extended fragments
      of MMP.

PMID- 9008848
TI  - The structure of stewartan, a capsular polysaccharide produced by Erwinia
      stewartii strain DC283.
AB  - Stewartan is a capsular polysaccharide produced by Erwinia stewartii, the
      causative agent of Stewart's wilt of maize. The structure of stewartan is shown,
      by a combination of methylation analysis, Li/ethylenediamine degradation, 1D and
      2D NMR spectroscopy, partial acid hydrolysis and isolation of oligosaccharides,
      Smith degradation, MALDI-TOFMS analysis and exoglycosidase digestion, to have the
      following repeating unit: [sequence: see text]

PMID- 9008849
TI  - Synthesis of alpha-D-Glcp-(1-->2)-alpha-D-Glcp-(1-->3) -alpha-D-Glcp-O-(CH2)8
      COOCH3 for use in the assay of alpha-glucosidase I activity.
AB  - The chemical synthesis of alpha-D-Glcp-(1-->2)-alpha-D-Glcp p-(1-->3) -alpha-D
      Glcp-O-(CH2)8 COOCH3 (9), a substrate specific for alpha-glucosidase I, is
      reported. This enzyme removes the terminal alpha-D-Glcp unit to produce alpha-D
      Glcp-(1-->3)-alpha-D-Glcp-O-(CH2)8 COOCH3 (10). This is the first synthetic
      substrate described for glucosidase I that allows kinetic evaluation of
      substrates and inhibitors of this enzyme. Tetramethylrhodamine was coupled to 9
      through an ethylenediamine linker to produce a brilliant red derivative. Addition
      of this fluorescent dye did not affect enzyme binding to the substrate, as
      determined by a comparison of the Km value (1.3 mM). The fluorescent label allows
      visual detection of 2-3 pmol of product by TLC.

PMID- 9008851
TI  - Synthesis of tetrasaccharides as possible metastatic inhibitors.
AB  - The synthesis is reported of the possible metastatic inhibitors-methyl beta-D
      galactopyranosyl-(1-->4) -(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-(1-->6) 
      beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside (11) and methyl beta-D
      galactopyranosyl- (1-->4)-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)- (1-->6)
      beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside (14)-by procedures for
      regio- and stereo-selective coupling, reduction of azido groups, N-acetylation,
      and O-deacetylation.

PMID- 9008850
TI  - Mechanism of anomerization of cyclohexyl 2-deoxy-3,4,6-tri-O-methyl-2-(N
      methylacetamido)-alpha- and beta-D-hexopyranosides under reductive-cleavage
      conditions.
AB  - The fully methylated cyclohexyl glycosides of 2-acetamido-2-deoxy-alpha- and beta
      D-hexopyranoses having the gluco, manno, and galacto configurations were each
      subjected to reductive-cleavage conditions using one of three promoters, namely
      trimethylsilyl trifluoromethanesulfonate, a mixture of trimethylsilyl
      methanesulfonate and boron trifluoride etherate, or boron trifluoride etherate
      alone. As expected, the fully methylated 1,2-trans-linked acetamido sugar
      derivatives were rapidly converted to their respective oxazolinium ions with all
      three promoters. Surprisingly, however, the fully methylated 1,2-cis-linked
      acetamido sugar derivatives were also converted to their respective oxazolinium
      ions, albeit at a much slower rate. In the latter case, evidence was obtained for
      anomerization to the 1,2-trans-linked isomers under reductive-cleavage
      conditions. Since the anomerization was relatively slow at room temperature in
      dichloromethane, a modified procedure was developed in which the reaction was
      carried out at 70 degrees C in 1,2-dichloroethane. Using the modified procedure,
      all 1,2-cis- and 1,2-trans-linked acetamido sugar derivatives were rapidly
      converted into their respective oxazolinium ions and subsequent quenching of the
      reactions with anhydrous methanol gave the respective 1,2-trans-linked methyl
      glycoside derivatives in quantitative yield. The modified procedure is
      recommended for the total reductive cleavage of polysaccharides comprised of
      acetamido sugar residues.

PMID- 9008852
TI  - Sulfated galactans from Australian specimens of the red alga Phacelocarpus
      peperocarpos (Gigartinales, Rhodophyta).
AB  - Polysaccharides from the red alga Phacelocarpus peperocarpos were extracted with
      hot water, clarified, and precipitated with 2-propanol. The native preparation
      was highly sulfated (36.2% w/w). Alkali modification decreased the sulfate
      content by 2.0% w/w. The alkali-modified polysaccharide is composed mostly of
      galactose (Gal. 51 mol%) and 3,6-anhydrogalactose (AnGal, 41 mol%), with minor
      amounts of a mono-O-methylgalactose (MeGal, 1 mol%), xylose (Xyl, 6 mol%), and
      glucose (Glc, 1 mol%). The FTIR spectrum of the alkali-modified polysaccharide
      resembled kappa-carrageenan with absorption at 930 cm-1 (indicative of AnGal) and
      850 cm-1 (Gal 4-sulfate). However, an additional, major band of absorption
      occurred sulfate ester substitution at O-6 of at 820 cm-1, indicating the
      presence of equatorial sulfate ester substitution at O-6 of Gal residues. A
      combination of linkage and 13C NMR spectroscopic analyses showed that the
      polysaccharide was composed predominantly of a novel repeating-unit, O-beta-D
      galactopyranosyl 4,6-disulfate)-(1-->4)-3,6-anhydro-alpha-D-galactopyranose.
      Minor structural variations also occurred, including alternative patterns of
      sulfation and the presence of terminal Xylp. The location of the terminal Xylp
      residues was not certain but evidence supported their attachment at O-3 of some 4
      linked Galp residues. The cell-wall galactans remain unchanged during the life
      cycle of the alga.

PMID- 9008853
TI  - Structural features of the pectic polysaccharides isolated from retted hemp bast
      fibres.
AB  - Pectic polysaccharides were solubilized from retted hemp bast fibre bundles, by
      sequential extraction with water and ammonium oxalate at 100 degrees C. The
      polysaccharides isolated from the extracts were de-esterified and fractionated by
      anion exchange chromatography, yielding five fractions from boiling water extract
      and five fractions from oxalate characterized by chemicals methods, 1H and 13C
      NMR, as extract. Five of these fractions were characterized by chemicals methods,
      1H and 13C NMR, as polysaccharides containing galacturonic acid, rhamnose and
      galactose units in variable ratios. Their chemical structure comprises a
      disaccharide repeating unit-->2)-alpha-L-Rhap-(1-->4)-alpha-GalpA-(1-->backbone,
      with short side chains attached to the rhamnosyl residues. The beta-D-Galactose
      residues are attached to O-4 of the rhamnosyl residues, but the amount of L
      rhamnosyl residues that are 2,4-linked can vary from 36 to 75%, from one fraction
      to another. A fraction corresponding to a mixture of oligosaccharides with an
      average dp of 13, with ten galacturonic acid, two rhamnose and one galactose
      units was also isolated.

PMID- 9008854
TI  - Synthesis and semisynthesis of alpha-D-mannopyranosyl-(1-->2)-alpha-D-
      mannopyranose octaacetate.

PMID- 9008855
TI  - Combined use of temperature and solvent strength in reversed-phase gradient
      elution. I. Predicting separation as a function of temperature and gradient
      conditions.
AB  - It has been shown previously that computer simulation based on two initial
      experiments can predict separation in reversed-phase gradient elution as a
      function of gradient conditions (gradient steepness, gradient range and gradient
      shape) and column conditions (column length, flow-rate and particle size). The
      present study extends this capability for changes in temperature. Four initial
      experiments (two different gradient times, two different temperatures) provide
      input data that allow predictions of separation as a function of temperature as
      well as gradient and column conditions. A semi-empirical relationship, tR = a +
      bT, is able to relate gradient retention time tR to column temperature T (other
      conditions constant). The accuracy of this approach has been evaluated for 102
      solutes and a variety of experimental conditions, including the use of five
      different HPLC instruments (four different models).

PMID- 9008856
TI  - Effects of fused tryptophan rich peptides to a recombinant protein. A domain on
      the partitioning in polyethylene glycol-dextran and Ucon-dextran aqueous two
      phase systems.
AB  - Genetic engineering has been used to construct fusion proteins with tryptophan
      containing peptides. The peptides and the fusion proteins have been partitioned
      in aqueous two-phase systems of poly(ethylene glycol) (PEG)-dextran and Ucon
      dextran. The studied model protein was ZZT0, where Z is an engineered domain of
      domain B of staphylococcal protein A. The specially designed hydrophobic
      peptides, Ala-Trp-Trp-Pro (T1) and (Ala-Trp-Trp-Pro)2 (T2), have been inserted
      into ZZT0, to give the peptide-protein fusions ZZT1 and ZZT2. In the experimental
      studies it was found that T1 and T2 preferred the PEG phase and even more the
      Ucon phase over the dextran phase. For T2 the partitioning was more one sided
      than for T1. For the fusion proteins, ZZT1 and ZZT2, the partitioning was
      enhanced into the PEG or Ucon rich phase as compared to ZZT0. The effects were
      lower than expected from independent contributions to the partition coefficient
      from the protein and the peptides. A heterogeneous lattice model was used to
      calculate theoretical peptide and protein partition coefficients. The
      calculations could reproduce the qualitative features of the experimental data.
      The model results suggest that a part of these experimentally observed effects is
      due to a depletion zone, i.e. a zone of reduced polymer concentration around the
      protein. The experimental results indicate a further reduction of the partition
      coefficient, beyond that predicted by the lattice calculations. A possible
      folding of the inserted peptide is discussed as a plausible mechanism for this
      further reduction in the partition coefficient.

PMID- 9008857
TI  - Application of spherical and other polymers in capillary zone electrophoresis:
      separation of antiviral drugs and deoxyribonucleoside phosphates by different
      principles.
AB  - Soluble polymers of linear chains with limited branching and spherical polymers
      (limit dextrins and sucrose, such as Dextran and Ficoll (Pharmacia Chemicals),
      yielding lower viscosities, are examined here for the separation of different
      nucleotides and several anti-AIDS drugs by capillary zone electrophoresis (CZE).
      The linear polymer forms a network but spherical polymers appear to create a
      second pseudo-phase. In general, they tend to enhance the solute mobility and
      reduce peak width; thus, they improve the column efficiency. We observe that the
      beads of a spherical polymer produce a pseudo-phase even in a very low polymer
      concentration. The proposed method involving a spherical polymer yields the best
      separation for twelve deoxyribonucleoside mono-, di- and triphosphates in ca. 10
      min. Common anti-AIDS drugs (ddA, ddC, ddI, d4T, AZT) and an AZT metabolite (AZT
      glucuronate) are resolved by using conventional micellar electrokinetic capillary
      chromatography (MEKC). These results not only offer fast and highly sensitive
      detection techniques for the pharmacokinetics of nucleotides, drugs, and their
      metabolites, but they also demonstrate an application of the proposed second
      pseudo-phase involving spherical polymer beads in CZE separations.

PMID- 9008858
TI  - Isolation of cardenolides from a Brazilian cultivar of Digitalis lanata by
      rotation locular counter-current chromatography.
AB  - Cardenolides from a Brazilian cultivar of Digitalis lanata were isolated by
      rotation locular countercurrent chromatography (RLCC), employing dichloromethane
      methanol-water (5:6:4, v/v) as the solvent system. Highly pure lanatoside C was
      obtained from the Digitalis lanata hydromethanolic extract, pre-purified either
      by silica gel or reversed-phase chromatography.

PMID- 9008859
TI  - Inhibition of fear-potentiated startle can be detected after the offset of a
      feature trained in a serial feature-negative discrimination.
AB  - Using the fear-potentiated startle paradigm in rats, 4 experiments examined
      whether the inhibitory effect of a feature is evident after its offset following
      serial feature-negative discrimination training (A+ and X-->A-). When startle
      probes were presented shortly after the offset of X on X-->A test trials, the
      inhibitory properties of X were observed immediately after its offset.
      Furthermore, trace reinforcement of X (X-->+), but not delay reinforcement (X+),
      disrupted the ability of X to inhibit fear-potentiated startle on X-->A trials.
      Trace conditioning to X was also retarded after A+ and X-->A- training. These
      results suggest that the inhibitory properties of the serially trained feature
      are present after its offset and raise the possibility that either temporal
      information regarding nonreinforcement or poststimulus attributes of X acquire
      inhibitory properties.

PMID- 9008860
TI  - CSs and USs: what's the difference?
AB  - Differences in processing representations of conditioned and unconditioned
      stimuli (CSs and USs) may result from either their temporal order in training
      (i.e., CSs precede USs) or the greater biological significance of USs. The CS-
      and US-preexposure effects were used to probe this question. These effects are
      similar except that context extinction between preexposure and training more
      readily attenuates the US- than the CS-preexposure effect. In Experiments 1, 2,
      and 5, context extinction following preexposure to the stimulus that later served
      as Event 1 in Event 1-->Event 2 pairings alleviated the response deficit due to
      Event 1 preexposure if Event 1 was biologically significant. In Experiments 3 and
      4, context extinction alleviated the response deficit due to Event 2 preexposure
      if Event 2 was biologically significant. Thus, biological significance and not
      temporal order determines how a representation will be processed.

PMID- 9008861
TI  - Language-naive chimpanzees (Pan troglodytes) judge relations between relations in
      a conceptual matching-to-sample task.
AB  - Three chimpanzees with a history of conditional and numeric token training
      spontaneously matched relations between relations under conditions of
      nondifferential reinforcement. Heretofore, this conceptual ability was
      demonstrated only in language-trained chimpanzees. The performance levels of the
      language-naive animals in this study, however, were equivalent to those of a 4th
      animal--Sarah--whose history included language training and analogical problem
      solving. There was no evidence that associative factors mediated successful
      performance in any of the animals. Prior claims of a profound disparity between
      language-trained and language-naive chimpanzees apparently can be attributed to
      prior experience with arbitrary tokens consistently associated with abstract
      relations and not language per se.

PMID- 9008862
TI  - Context dependency of conditioned aversions to water and sweet tastes.
AB  - Three experiments exposed rats (Rattus norvegicus) to a discriminative
      conditioning procedure whereby a specific fluid was followed by lithium in one
      environment but not in another. This produced context-specific aversion to water,
      as detected by 2-bottle tests in Experiment 1, and a context-dependent saccharin
      aversion, which was unaffected by context extinction, in Experiment 2. Experiment
      3 found that sucrose preexposure increased contextual control over the aversion
      established by sucrose-lithium pairings but had no effect on the target context.
      By contrast, target context exposure during conditioning reduced aversion to this
      context but did not affect contextual control of the sucrose aversion. In
      conclusion, depending on the conditioning procedures, contextual control of a
      taste aversion can be independent of the context's Pavlovian properties.

PMID- 9008863
TI  - Mnemonics for variability: remembering food delay.
AB  - Three experiments with White Carneaux pigeons (Columba livia) investigated memory
      and decision processes under fixed and variable reinforcement intervals. Response
      rate was measured during the unreinforced trials in the discrete-trial peak
      procedure in which reinforced trials were mixed with long unreinforced trials.
      Two decision models differing in assumptions about memory constraints are
      reviewed. In the complete-memory model (J. Gibbon, R.M. Church, S. Fairhurst, &
      A. Kacelnik, 1988), all interreinforcement intervals were remembered, whereas in
      the minimax model (D. Brunner, A. Kacelnik, & J. Gibbon, 1996), only estimates of
      the shortest and longest possible reinforcement times were remembered. Both
      models accommodated some features of response rate as a function of trial time,
      but only the second was compatible with the observed cessation of responding.

PMID- 9008864
TI  - Temporal specificity in serial feature-positive discrimination learning.
AB  - Two experiments examined the temporal specificity of learning in operant serial
      feature-positive discriminations (feature-->target+/target-). Test performance
      was better when the target cues were presented at their customary times after the
      features than when they were presented at earlier or later times. When features
      trained with one feature-target interval were combined with targets trained with
      another interval, performance was best when the test interval was the same as the
      interval associated with the feature, suggesting that the temporal information
      was coded with the feature cue. Finally, the temporal specificity of the
      responding controlled by occasion setters was unaffected by feature extinction.
      Implications for the nature of learning in occasion setting are discussed.

PMID- 9008865
TI  - Blocking in the spatial domain.
AB  - An initial series of experiments with rats in a swimming pool established that
      they could find a hidden platform the location of which was defined in terms of 3
      or 4 landmarks and that, when trained with all 4, any subset of 3 (or even, after
      a sufficient number of swimming trials, 2) landmarks was sufficient to produce
      accurate performance. When only one landmark was present during testing, however,
      performance fell to chance. Two additional experiments demonstrated a significant
      blocking effect: If rats were first trained to locate the platform with 3
      landmarks, they did not learn to use a 4th landmark added to their initial set of
      3.

PMID- 9008866
TI  - Column-switching high-performance liquid chromatography combined with ionspray
      tandem mass spectrometry for the simultaneous determination of the platelet
      inhibitor Ro 44-3888 and its pro-drug and precursor metabolite in plasma.
AB  - A liquid chromatographic/mass spectrometric (LC/MS) assay was developed for the
      simultaneous determination of a pro-drug (Ro 48-3657), its active metabolite
      (platelet inhibitor, Ro 44-3888) and precursor metabolite (Ro 48-3656) in human,
      dog and rat plasma, utilizing on-line column-switching solid-phase extraction
      (SPE) for clean-up and high-performance liquid chromatography (HPLC) for
      separation of the analytes, with on-line detection by ionspray (pneumatically
      assisted electrospray) tandem mass spectrometry in the selected reaction
      monitoring (SRM) mode. The assay was validated for the quantification of all
      three analytes. The method involves protein precipitation with perchloric acid,
      enrichment of the analytes on a standard bore trapping column (i.d. 4.6 mm) and
      separation on a narrow-bore analytical column (i.d. 2 mm). Except for the plasma
      precipitation step, the assay was fully automated, allowing unattended operation.
      The lower limits of quantification were 0.20 ng ml-1 (Ro 48-3657, Ro 44-3888) and
      0.50 ng ml-1 (Ro 48-3656) using a 0.5 ml plasma aliquot. The mean inter-assay
      precision and accuracy derived from quality control samples were 5.3% and 101%,
      respectively, utilizing the calibration range 0.2-200 ng ml-1. Using the unique
      features of column-switching HPLC combined with MS/MS, it was possible to develop
      the method in a short period of time. The method has been successfully applied to
      map complete concentration-time courses for the kinetic evaluation of the drug
      and its metabolites in man, dog and rat. This LC/MS assay is sensitive, specific,
      accurate, precise and robust.

PMID- 9008867
TI  - Mass spectrometric characterization of the beta-subunit of human chorionic
      gonadotropin.
AB  - A high-performance liquid chromatographic/electrospray mass spectrometric
      (HPLC/MS) technique is described for the characterization of the beta-subunit of
      the glycopeptide human chorionic gonadotropin (hCG). The beta-subunit of hCG was
      dissociated from the alpha-subunit using 0.1% trifluoroacetic acid (TFA) and
      separated by reversed-phase HPLC using a 0.1% TFA-acetonitrile gradient. Although
      reductive alkylation with 4-vinylpyridine allowed direct observation of the
      intact beta-subunit of hCG by HPLC/MS due to the increase in charge, the
      heterogeneity of the carbohydrate fractions resulted in poor detection limits and
      extremely complex spectra. After reductive alkylation with either iodoacetate or
      4-vinylpyridine, tryptic fragments of either the alpha- or beta-subunit can be
      observed using reversed-phase HPLC/MS. HPLC/MS data were consistent with the
      reported primary sequence, although oligosaccharide attachment sites at both
      127Ser and 132Ser could not be documented. Microheterogeneity of the carbohydrate
      moiety on both N-glycosylation sites on the beta-subunit could be readily
      observed. A larger degree of heterogeneity was observed on 13Asn. Differences
      were also observed in the oligosaccharide distribution in three commercial
      preparations of hCG. Detection of the C-terminal portion of the beta-subunit
      required enzymatic deglycosylation prior to HPLC/MS analysis.

PMID- 9008868
TI  - Gas-phase protonation of pyridine. A variable-time neutralization-reionization
      and Ab initio study of pyridinium radicals.
AB  - Gas-phase protonation of pyridine with CH3NH3+, NH4+, t-C4H9+, H3O+ and CH5+
      under thermal conditions was studied by variable-time neutralization-reionization
      mass spectrometry and ab initio calculations. N-Protonation was found to occur
      exclusively for CH3NH3+ through H3O+ and predominantly for CH5+. The calculated
      MP2/6-311G(2d,p) energies gave the proton affinities of N, C-2, C-3 and C-4 in
      pyridine as 924, 658, 686 and 637 kJ mol-1, respectively, which were in good
      agreement with previous experimental and theoretical results. Vertical
      neutralization of the N-protonated isomer (1H+) was accompanied by moderate
      Franck-Condon effects that deposited 20-21 kJ mol-1 in the 1H-pyridinium radicals
      (1H) formed. 1H was calculated by UMP2/6-311G(2d,p) and B3LYP/6-311G(2d,p) to be
      a bound species in its ground electronic state. A substantial fraction of stable
      1H was detected in the spectra, which depended on the precursor ion internal
      energy. Deuterium labeling showed a specific loss of the N-bound hydrogen or
      deuterium in the radicals. The specificity increased with increasing internal
      energy in the radicals and decreasing contribution of ion dissociations following
      reionization. Variable-time measurements established specific loss of the N-bound
      deuterium also in dissociating low-energy 1D. Loss of hydrogen from 1H+ cations
      following reionization was highly endothermic and was accompanied by
      rearrangements that partially scrambled the ring hydrogens.

PMID- 9008869
TI  - High-performance liquid chromatography/NMR spectrometry/mass spectrometry:
      further advances in hyphenated technology.
AB  - The earlier use of combined liquid chromatography/NMR spectrometry/mass
      spectrometry (LC/NMR/MS) involved the use of a particle beam interface. This
      paper describes further developments of this hyphenated technology, in particular
      the incorporation of an electrospray interface into the LC/NMR/MS system. This
      improved LC/NMR/MS system was designed for the support of a combinatorial library
      program. The power of this technique is demonstrated in the successful structural
      elucidation of each compound in a mixture of commercially available peptides.

PMID- 9008870
TI  - Investigation of group migration in the fragmentation of bis(trimethylsilyl)
      ethers of diols separated by rigid groups.
AB  - Two fragmentations of (CH3)3SiO-CR2-X-CR2-OSi(CH3)3, where X is a rigid group
      such as a triple bond or an aromatic ring, are losses of a methyl or R group
      (where R is H or alkyl). The metastable-ion dissociations of [M-R]+ and [M-CH3]+
      ions include the rearrangement of a trimethylsilyl (TMS) cation and a (CH3)2Si =
      O neutral species through an ion-neutral complex. On the basis of tandem mass
      spectrometry (MS/MS), exact mass measurement and isotopic labeling experiments,
      it has been established that the two trimethylsilyloxy groups in the TMS ethers
      interact across a wide range of distances via an ion-neutral complex. The
      migration of a TMS cation occurs when the group that is bound to carbon is
      expelled as a radical by an oxygen-directed cleavage to give a trimethylsilylated
      oxonium ion. If, on the other hand, a methyl radical is lost from the silicon
      atom, then (CH3)2Si = O migrates. The mobilities of the TMS cation and the
      neutral (CH3)2Si = O are governed by the capability of the rigid group to
      delocalize charge.

PMID- 9008871
TI  - Measuring lipogenesis and cholesterol synthesis in humans with deuterated water:
      use of simple gas chromatographic/mass spectrometric techniques.
AB  - Lipogenesis and cholesterol synthesis can be studied by measuring the
      incorporation into fatty acids and cholesterol of deuterium from deuterated
      water. This has been previously achieved in human subjects using low levels of
      deuterium enrichment in plasma water, and thus in fatty acids and cholesterol.
      For the measurement of enrichment in lipids, this required the use of isotope
      ratio mass spectrometry, a tedious and time-consuming technique. It is shown that
      these measurements can be performed using the much simpler gas
      chromatography/mass spectrometry if higher, but always safe, deuterium
      enrichments in plasma water are obtained. Normal subjects ingested deuterated
      water in order to obtain stable enrichment in plasma water of 0.3% during a 60 h
      period. Enrichment in palmitate of plasma triglycerides (TG) plateaued (0.6
      0.76%) whereas plasma cholesterol enrichment increased progressively [0.32 +/-
      0.08% (12 h) to 0.78 +/- 0.18% (60 h)]. Endogenous synthesis was estimated to
      contribute, in post-absorptive subjects, 8-10% of the plasma TG pool and 3-5% of
      plasma free cholesterol pool. These data agree with results obtained previously
      using isotope ratio mass spectrometry. The present method will be useful for
      studies of normal and abnormal lipid metabolism in humans.

PMID- 9008872
TI  - Isotope ratio mass spectrometric method for the on-line determination of oxygen
      18 in organic matter.
AB  - A method for the on-line determination of oxygen-18, at a naturally occurring
      level, in organic material is presented. After pyrolysis of the samples to form
      carbon monoxide, which is performed at 1300 degrees C in a vitreous carbon tube,
      the pyrolysis products are transported by a stream of helium gas. Using an open
      split, a small part of the effluent is transferred to the ion source of an
      isotope ratio mass spectrometer. The ratio is obtained from a measurement of the
      ion current intensities at m/z 30 and 28 (12C18O and 12C16O). The method was
      tested with the secondary water standard GISP (Greenland Ice Sheet Precipitation)
      and the carbonate standard NBS 19. The values obtained were -24.8/1000 and
      27.3/1000 vs. VSMOW (Vienna Standard Mean Ocean Water) (LAEA reference values are
      -24.8/1000 and 28.7/1000 vs. VSMOW). The potential of the method was demonstrated
      by measuring the 18O content of samples of beet and cane sucrose and also samples
      of vanillin extracted from vanilla pods or of synthetic origin.

PMID- 9008873
TI  - Electrospray tandem mass spectrometry of a novel series of amphipathic
      functionalized ether-linked di- and trisaccharides and cyclic oligosaccharides.
AB  - Electrospray mass spectrometry (ESMS) has aided the structural characterization
      of a novel series of amphipathic functionalized ether-linked di- and
      trisaccharides, composed of units of alkyl derivatives of glucofuranose and
      either units of glucofuranose or diacetylgalactose. The structural elucidation of
      a novel eight-membered macrocyclic ether-linked disaccharide and an 11-membered
      macrocyclic ether-linked trisaccharide was also effected using ESMS. Low-energy
      collision-induced dissociation MS/MS analysis of the [M + H]+ precursor ions
      confirmed the characteristic fingerprint patterns obtained in the conventional
      electrospray spectra and proved to be a specific and very sensitive method for
      the detection and characterization of these novel amphipathic molecules.

PMID- 9008874
TI  - Molecular mass tagging to one strand of polymerase chain reaction products.

PMID- 9008875
TI  - Improved immunogold labeling of epoxy sections by the use of propylene oxide as
      additional agent in dehydration, infiltration and embedding.
AB  - The purpose of this study was to examine how the intensity of the immunogold
      labeling on epoxy sections was affected by the use of propylene oxide as an agent
      in addition to ethanol in the dehydration and infiltration, and also to examine
      the effect on the immunogold labeling by adding small amounts of propylene oxide
      to the embedding mixture. Increased knowledge of the mechanism for antigen
      detection on resin sections was another aim. Thyroid tissue, kidney tissue, and
      fibrin were embedded in epoxy resin; some with ethanol as the only dehydration
      agent and others with propylene oxide as an additional agent in dehydration,
      infiltration or embedding steps in different ways. Immunogold labeling was
      performed with anti-thyroglobulin, anti-IgG, and anti-fibrinogen, respectively. A
      higher degree of immunogold labeling was achieved by increasing the concentration
      of accelerator during infiltration and embedding (Brorson and Skjorten, 1996a,
      Micron, 27, 211-217). The immunogold labeling of the sections that were based on
      additional dehydration and infiltration with propylene oxide showed significantly
      more intense labeling than the sections of tissues that had only been exposed to
      ethanol in the dehydration and infiltration steps. The embedding of tissues in a
      mixture of epoxy resin and 5-10% propylene oxide gave higher yields of immunogold
      labeling than if pure epoxy resin was used for the embedding. The improved
      labeling is explained by higher amplitudes of protruding antigens on the surface
      of the sections because antigens are less tightly incorporated in the polymer
      network when using propylene oxide as additional agent in dehydration,
      infiltration or embedding. These results illustrate the advantage of using
      propylene oxide as an additional agent when preparing specimens for
      immunoelectron microscopy with epoxy resin embedding.

PMID- 9008876
TI  - The structure of the mandibular condyle in the monkey (Macaca mulatta).
AB  - The articulating surfaces of bones which ossify in mesenchyme, like the mandible,
      are covered by a layer of dense, fibrous tissue. The purpose of the present study
      was to examine the structure of the mandibular condyle in the monkey. Young
      Rhesus monkeys (Macaca mulatta) were perfused with glutaraldehyde
      paraformaldehyde. Small pieces of the condyles were dissected out, demineralized
      in 0.5 M EDTA and processed for light microscopy and electron microscopy. The
      mandibular condyle was covered by an avascular tissue, extending from the surface
      to the underlying bone. The tissue could be divided into three zones. The zone
      facing the articular cavity was about 50 microns wide and consisted of a dense,
      fibrous tissue. Layers of collagen fibers, 1-4SS microns wide and parallel with
      the articular surface, but oriented at angles to each other, were seen. Between
      the collagen fibers fibroblast-like cells were noted. The second zone was also
      approximately 50 microns wide and rich in cells. The cells were ovoid or flat and
      had a dark staining cytoplasm with some mitochondria and a well developed rough
      surfaced endoplasmic reticulum. The third zone was about 150 microns wide and
      here the cells were larger and located in lacunae. An increase in the size of
      cells and lacunae was seen approaching the bone. This zone showed hyaline
      cartilage undergoing maturation. Closer to the bone, degeneration of the
      chondrocytes was noted. In the underlying bone, soft tissue with several
      chondroclasts resorbing the hypertrophic cartilage were seen, alternating with
      areas where bone formation was occurring, partly on the top of cartilage
      remnants. The observations confirm that in the growing condyle there is an
      articular part as well as a growth zone, and that the cells in the cell-rich zone
      serve as precursors for the hyaline cartilage cells in the growth zone, and
      possibly as a cell reservoir for the articular part as well.

PMID- 9008877
TI  - Killer factor interference in mixed opportunistic yeast cultures.
AB  - The interaction of the killer yeast Pichia anomala UP 25F with the killer toxin
      sensitive clinical isolate Candida albicans UCSC 10S and its natural toxin
      resistant mutant derivative C. albicans UCSC 10R were studied under various
      conditions. A differential inhibition was shown to occur in vitro at pH and
      temperature values, which are not encountered in vivo, only by using preformed
      killer toxin, since antagonism due to yeast growth proved to be predominant on
      the killer effect. Under adverse growth conditions, the P. anomala killer yeast
      proved to be able to produce an anatoxin antigenically related to the active or
      heat inactivated killer toxin. These findings suggest that killer toxins may not
      function as potential virulence factors in the competition between the
      opportunistic killer yeast P. anomala and sensitive microorganisms for
      colonization in the course of natural human infections.

PMID- 9008878
TI  - Otomycosis--a clinico-mycological study and efficacy of mercurochrome in its
      treatment.
AB  - A total of 110 patients of symptomatic otomycosis was investigated,
      prospectively. Aural swabs were collected on 1st, 7th and 14th day and examined
      by direct microscopy and culture for fungi. Of these, 80 patients found to be
      having pure fungal infection, were taken up for mycological and therapeutic
      study. Fungi belonging to genus Aspergillus were isolated in 76 (95.0%) patients
      of which Aspergillus niger was the commonest isolate in 46 (57.5%), followed by
      A. flavus in 27 (33.7%), A. fumigatus in 3 (3.7%), Candida species in 3 (3.7%)
      and Mucor in 1 (1.2%). The patients were of all age groups but majority were
      between 21 and 30 years and the male-female ratio was equal. Of the total of 40
      male patients, twenty-one were Sikhs using turban. Before developing the
      symptoms, forty five patients used oil, mixture of oil and garlic juice,
      antibiotics, steroids, antiseptics or wax solvent as ear drops. Only two patients
      were diabetic. No patient had fungal infection elsewhere in the body. The
      patients were called for regular follow-up for three weeks. In forty cases
      mercurochrome was applied as the antifungal agent after cleaning the external
      auditory canal, in twenty-three clotrimazole and in rest of the seventeen
      patients miconazole was used. On 7th day, only 11 (13.7%) patients grew different
      fungi in culture. They became symptom-free on 14th day and no fungal material
      could be seen on otoscopy, direct microscopy or culture. Mercurochrome was found
      to be most effective in these patients.

PMID- 9008879
TI  - Paracoccidioides brasiliensis antigen batches from the same isolate show
      immunological and biochemical differences.
AB  - We investigated the occurrence of antigenic and biochemical variability among
      Paracoccidioides brasiliensis antigen batches prepared according to the same
      protocol. Initially (experiment #1), we analyzed two antigen lots of two human
      isolates (Bt1 & Bt2), cultured in two media (PYG: bactopeptone, yeast extract,
      glucose; MMM: McVeigh & Morton medium) in SDS-PAGE and in two immunological tests
      (immunodiffusion-ID and footpad swelling test-FPT). Afterwards (experiment #2),
      we compared the antigenic profile of three antigen batches from three human
      isolates (Bt1, Bt2 & Bt3) by two-dimensional immunoelectrophoresis (2 D-IEP)
      against a reference system for P. brasiliensis antigens. In experiment #1, there
      were important intra- and inter-strain antigenic differences between batches of
      the fungal isolates cultured on both media. The block titration of the antigen
      batches for the immunological tests revealed correlation between protein
      concentration and biological activity in ID and no correlation in FPT. In
      experiment #2, the reference system for P. brasiliensis showed 26 antigen peaks.
      There were important differences between batches prepared from the same isolate
      and between batches from different isolates. Our data suggested the occurrence of
      instability in the synthesis of antigenic components by a same P. brasiliensis
      isolate, under controlled incubation conditions.

PMID- 9008880
TI  - Effect of medicating ingredients and other additives on microflora present on
      swine and chicken feeds from a Manitoba mill.
AB  - The occurrence of microfloral components on medicated and non-medicated swine and
      chicken feed pellets and crumbles, produced in a Manitoba feed mill between June
      1991 and October 1992, was determined. Addition of medicates to feeds generally
      decreased bacterial incidence and increased that of Eurotium spp. fungi. The
      effect was less pronounced when copper sulphate was added to medicated swine
      feeds.

PMID- 9008881
TI  - Simultaneous formation of peptides and nucleotides from N-phosphothreonine.
AB  - An intramolecular mutual activation between a phosphoryl group and carboxyl group
      results in the simultaneous formation of nucleotides and peptides by the reaction
      of nucleosides with N-(O,O-diisopropyl)phosphothreonine in anhydrous pyridine.
      These results suggest pathways for the simultaneous prebiotic synthesis of
      peptides and oligonucleotides.

PMID- 9008883
TI  - Biodegradation of polyhydroxyalkanoic acids.
AB  - Stimulated by the commercial availability of bacteriologically produced
      polyesters such as poly[(R)-3-hydroxybutyric acid], and encouraged by the
      discovery of new constituents of polyhydroxyalkanoic acids (PHA), a considerable
      body of knowledge on the metabolism of PHA in microorganisms has accumulated. The
      objective of this essay is to give an overview on the biodegradation of PHA. The
      following topics are discussed: (i) general considerations of PHA degradation,
      (ii) methods for identification and isolation of PHA-degrading microorganisms,
      (iii) characterization of PHA-degrading microorganisms, (iv) biochemical
      properties of PHA depolymerases, (v) mechanisms of PHA hydrolysis, (vi)
      regulation of PHA depolymerase synthesis, (vii) molecular biology of PHA
      depolymerases, (viii) influence of the physicochemical properties of PHA on its
      biodegradability, (ix) degradation of polyesters related to PHA, (x)
      biotechnological aspects of PHA and PHA depolymerases.

PMID- 9008882
TI  - The beta-sheets of proteins, the biosynthetic relationships between amino acids,
      and the origin of the genetic code.
AB  - Two forces are generally hypothesised as being responsible for conditioning the
      origin of the organization of the genetic code: the physicochemical properties of
      amino acids and their biosynthetic relationships (relationships between precursor
      and product amino acids). If we assume that the biosynthetic relationships
      between amino acids were fundamental in defining the genetic code, then it is
      reasonable to expect that the distribution of physicochemical properties among
      the amino acids in precursor-product relationships cannot be random but must,
      rather, be affected by some selective constraints imposed by the structure of
      primitive proteins. Analysis shows that measurements representing the 'size' of
      amino acids, e.g. bulkiness, are specifically associated to the pairs of amino
      acids in precurso-product relationships. However, the size of amino acids cannot
      have been selected per se but, rather, because it reflects the beta-sheets of
      proteins which are, therefore, identified as the main adaptive theme promoting
      the origin of genetic code organization. Whereas there are no traces of the alpha
      helix in the genetic code table. The above considerations make it necessary to re
      examine the relationship linking the hydrophilicity of the dinucleoside
      monophosphates of anticodons and the polarity and bulkiness of amino acids. It
      can be concluded that this relationship seems to be meaningful only between the
      hydrophilicity of anticodons and the polarity of amino acids. The latter
      relationship is supposed to have been operative on hairpin structures, ancestors
      of the tRNA molecule. Moreover, it is on these very structures that the
      biosynthetic links between precursor and product amino acids might have been
      achieved, and the interaction between the hydrophilicity of anticodons and the
      polarity of amino acids might have had a role in the concession of codons
      (anticodons) from precursors to products.

PMID- 9008884
TI  - Do the non-catalytic polysaccharide-binding domains and linker regions enhance
      the biobleaching properties of modular xylanases?
AB  - Xylanase A (XylA) from Pseudomonas fluorescens subsp. cellulosa consists of an N
      terminal non-catalytic cellulose-binding domain joined to a functionally
      independent C-terminal catalytic domain by a sequence rich in serine residues.
      Xylanase D (XylD) from Cellulomonas fimi also exhibits a modular structure
      comprising an N-terminal catalytic domain linked to an internal non-catalytic
      xylan-binding domain and a C-terminal cellulose-binding domain. To determine the
      importance of the non-catalytic polysaccharide-binding domains and linker
      sequences of XylA and XylD in relation to their capacity to hydrolyse pulp xylan
      and enhance bleachability, purified full-length and modified derivatives of both
      enzymes were incubated with a hardwood kraft pulp. Deletion of the cellulose
      binding domain or linker region from XylA decreased the activity of the enzyme
      against pulp xylan, but had no significant effect on the capacity of the enzyme
      to facilitate delignification and reduce pulp kappa number. While full-length and
      truncated forms of XylD, lacking either the cellulose-binding or the cellulose-
      and xylan-binding domains, were equally effective in hydrolysing pulp xylan,
      enzyme derivatives containing a polysaccharide-binding domain were marginally
      more efficient in reducing pulp kappa number. The reduction in kappa number
      elicited by full-length and isolated catalytic domains of XylA and XylD was
      reflected in an increase in the brightness of paper handsheets derived from
      pretreated pulps. Thus, the polysaccharide-binding domains of XylA and XylD did
      not appear to confer any advantage in terms of the ability of the enzymes to
      improve pulp bleachability. However, XylA and XylD, which belong to different
      glycosyl hydrolase families, differed in their ability to hydrolyse pulp xylan
      and facilitate the delignification of kraft pulp.

PMID- 9008885
TI  - High volumetric yields of functional dimeric miniantibodies in Escherichia coli,
      using an optimized expression vector and high-cell-density fermentation under non
      limited growth conditions.
AB  - Functional bivalent miniantibodies, directed against the epidermal growth factor
      receptor, accumulated to more than 3 gl-1 in high-cell-density cultures of
      Escherichia coli RV308(pHKK) on a pilot scale. The miniantibodies consist of scFv
      fragments with a C-terminal hinge followed by a helix-turn-helix motif, which
      homodimerizes in vivo. The improved expression vector pHKK is characterized by
      the hoklsok suicide system, improving plasmid maintenance, and the inducible lac
      pl o promoter system with the very strong T7g10 Shine-Dalgarno sequence. The
      expression unit is flanked by terminators. The prototrophic RV308 cells were
      cultivated in glucose mineral salt medium and reached a cell density of 145 g dry
      biomass l-1 after 33 h. After induction, growth continued almost unchanged for a
      further 4 h with concomitant miniantibody formation. In the fedbatch phase, the
      concentration of glucose was kept almost constant at the physiological level of
      approximately 1.5 gl-1, using on-line flow injection analysis for control.
      Surprisingly, E. coli RV308(pHKK) did not accumulate significant amounts of the
      metabolic by-product acetate under these unlimited aerobic growth conditions.

PMID- 9008886
TI  - Expression of the hepatitis B virus surface antigen in mammalian cells using an
      Epstein-barr-virus-derived vector.
AB  - The hepatitis B virus surface antigen (HBsAg) gene, under control of the
      inducible mouse metallothionein I gene promoter, was inserted in an expression
      vector based on the Epstein-Barr virus (EBV). This vector was introduced into
      human cells by DNA transfection and clones were selected for their resistance to
      hygromycin B. The recombinant EBV vector replicates efficiently as an episome in
      human cells and approximately six copies per cell were found in one clone of
      hygromycin-B-resistant cells. These cells produce high levels of HBsAg in the
      presence of metals. The protein is mainly found in the cell medium, suggesting
      that the HBsAg is secreted from the cells.

PMID- 9008887
TI  - Molecular cloning, purification and characterization of two endo-1,4-beta
      glucanases from Aspergillus oryzae KBN616.
AB  - Two endo-1,4-beta-glucanase genes, designated celA and celB, from a shoyu koji
      mold Aspergillus oryzae KBN616, were cloned and characterized. The celA gene
      comprised 877 bp with two introns. The CelA protein consisted of 239 amino acids
      and was assigned to the cellulase family H. The celB gene comprised 1248 bp with
      no introns. The CelB protein consisted of 416 amino acids and was assigned to the
      cellulase family C. Both genes were overexpressed under the promoter of the A.
      oryzae taka-amylase A gene for purification and enzymatic characterization of
      CelA and CelB. CelA had a molecular mass of 31 kDa, a pH optimum of 5.0 and
      temperature optimum of 55 degrees C, whereas CelB had a molecular mass of 53 kDa,
      a pH optimum of 4.0 and temperature optimum of 45 degrees C.

PMID- 9008888
TI  - Evaluation of the biological containment system based on the Escherichia coli gef
      gene in Pseudomonas aeruginosa W51D.
AB  - The cell-killing gef gene was introduced, under the control of the lac promoter
      and as part of a transposon, into Pseudomonas aeruginosa W51D, a strain able to
      degrade branched-chain alkylbenzene sulfonates. Only 1% of the cells that
      inherited the transposon (Tngef) showed a conditional lethal phenotype, and this
      phenotype was lost at a high frequency without apparent loss of the tetracycline
      resistance encoded by the transposon. Southern blot analysis of two W51D::Tngef
      derivatives that expressed the cell-killing function showed multiple insertions
      of the transposon. These data suggest that Gef protein is able to kill P.
      aeruginosa W51D, but it seems that the level of resistance to Gef toxin in this
      stain is higher than that of previously reported bacteria, and that the
      expression of multiple copies of the gef gene is necessary to attain cell death.
      The higher level of resistance does not seem to be particular to strain W51D
      since two other P. aeruginosa strains analyzed (PAO2003 and ATCC 9027) also
      presented a small proportion of cells expressing the conditional lethal phenotype
      when they inherited the Tngef transposon.

PMID- 9008889
TI  - Construction of L-lysine-overproducing strains of Brevibacterium lactofermentum
      by targeted disruption of the hom and thrB genes.
AB  - The mobilization of plasmids from gram-negative Escherichia coli to gram-positive
      Brevibacterium lactofermentum, mediated by P-type transfer functions, was used to
      construct disrupted mutants blocked specifically in the homoserine branch of the
      aspartate pathway. The mutant strain B. lactofermentum R31 showed an efficiency
      of conjugal transfer two to three orders of magnitude higher than that of the
      wild-type strain B. lactofermentum ATCC 13869. The hom- and thrB-disrupted
      mutants of B. lactofermentum ATCC 13869 were lysine overproducers. B.
      lactofermentum R31 mutants do not overproduce lysine because R31 is an alanine
      overproducing strain and channels the pyruvate needed for lysine biosynthesis to
      the production of alanine.

PMID- 9008890
TI  - Catabolite-repressor-like protein regulates the expression of a gene under the
      control of the Escherichia coli lac promoter in the plant pathogen Xanthomonas
      campestris pv. campestris.
AB  - Xanthomonas campestris pv. campestris, the causal agent of black-rot disease of
      cruciferous plants, and an important industrial microbe, was able to express the
      Escherichia coli beta-glucuronidase reporter gene (uidA) when fused to the E.
      coli lactose operon promoter on a wide-host-range plasmid vector. The gene fusion
      is expressed constitutively at high levels in both complex and defined media
      using a wide range of carbon sources, and is not repressible by glucose or
      inducible by the gratuitous lac inducer isopropyl beta-D-thiogalactoside. An X.
      campestris campestris strain with a lesion in the clp (catabolite-repressor-like
      protein) locus, and containing the placluidA fusion, was tested for beta
      glucuronidase activity. We found that the expression of the placluidA fusion gene
      is dependent on the presence of catabolite-repressor-like protein, with an
      approximately 75% reduction of expression in the clp -deficient mutant.

PMID- 9008891
TI  - The action of antibiotics on the anaerobic digestion process.
AB  - Antibiotics can disturb the production of biogas during anaerobic digestion. This
      study shows a systematic approach to understanding how the different bacterial
      populations involved in the final conversion of organic matter into methane are
      inhibited by 15 antimicrobial agents with different specificities and modes of
      action. The results obtained show the following trends: (i) some inhibitors, such
      as the macrolide erythromycin, lack any inhibitory effect on biogas production;
      (ii) some antibiotics, with different specificities, have partial inhibitory
      effects on anaerobic digestion and decrease methane production by interfering
      with the activity of propionic-acid- and butyric-acid-degrading bacteria, (e.g.
      antibiotics that interfere with cell wall synthesis, RNA polymerase activity and
      protein synthesis, especially the aminoglycosides); (iii) the protein synthesis
      inhibitors chlortetracycline (IC50 40 mg l-1) and chloramphenicol (IC50 15-20 mg
      l-1) are very powerful inhibitors of anaerobic digestion. The majority of the
      antibiotics tested lacked activity against acetoclastic methanogens, being active
      only on the acetogenic bacteria. However, chloramphenicol and chlortetracycline
      could cause the complete inhibition of the acetoclastic methanogenic archaea.

PMID- 9008892
TI  - Ozone-induced damage of Escherichia coli K-12.
AB  - Escherichia coli K-12 transformed with pA-CYC184 plasmid DNA was exposed to ozone
      (O3) in aqueous solution. The damage to the membrane, protein, plasmid DNA, and
      cell survival were investigated. Cell viability was unaffected by short-term O3
      exposure (1-5 min) but membrane permeability was compromised as indicated by
      protein and nucleic acid leakage and lipid oxidation. The intracellular
      components, protein and DNA, remained intact. With longer durations of O3
      exposure (up to 30 min) cell viability decreased with a more significant increase
      in lipid oxidation and protein and nucleic acid leakage. The proteins leaking out
      were further oxidized by O3. The total intracellular proteins run on sodium
      dodecyl sulfate/polyacrylamide gel electrophoresis, and plasmid DNA run on
      agarose gel, showed progressive degradation corresponding to the decrease in cell
      viability. The data indicate that membrane components are the primary targets of
      O3 damage with subsequent reactions involving the intracellular components,
      protein and DNA.

PMID- 9008893
TI  - Microbial removal of chlorinated phenols during aerobic treatment of effluents
      from radiata pine kraft pulps bleached with chlorine-based chemicals, with or
      without hemicellulases.
AB  - The removal of chlorophenolic compounds from kraft mill effluents bleached with
      chlorine (cBKME) or chlorine plus hemicellulases (bBKME) was studied in reactors
      of aerobic treatment lagoons. In these laboratory models, a stable microbial
      population removed biochemical oxygen demand at similar rates of the mill lagoon.
      Complete removal of nine chlorophenols and chloroguaiacols during microbial
      treatment of these effluents was detected by gas chromatography. Abiotic removal
      was only observed with 2,4-dichlorophenol and 2,4,5-trichlorophenol. There were
      no significant differences in degradative ability between microorganisms
      acclimated to grow in reactors fed with cBKME or bBKME. The latter had a lower
      content of adsorbable organic halogen and chlorophenols than cBKME.
      Microorganisms acclimated to cBKME or bBKME were only able to grow on phenol or
      guaiacol as sole carbon source. However, these microorganisms removed (0.1-0.5
      mM) 4-chlorophenol, 2,4-dichlorophenol and 2,4-dichlorophenoxyacetate with BKME
      as primary carbon source. Under these conditions, 2,4,6- and 2,4,5
      trichlorophenol, 4,5-dichloroguaiacol, 4,5,6-trichloroguaiacol and
      tetrachloroguaiacol were not removed. These results suggest that the microbial
      removal of bleaching chlorophenols and chloroguaiacols during aerobic treatment,
      probably takes place only because of their very low concentration (1-200 ppb) in
      BKME.

PMID- 9008894
TI  - Adding sodium dodecyl sulfate and Pseudomonas aeruginosa UG2 biosurfactants
      inhibits polycyclic aromatic hydrocarbon biodegradation in a weathered creosote
      contaminated soil.
AB  - The effect of two anionic surfactants was assessed during biodegradation of 13 of
      the 16 USEPA priority polycyclic aromatic hydrocarbons (PAH) in a wood-preserving
      soil contaminated with creosote and pentacholorophenol for a period of at least
      20 years. Sodium dodecyl sulfate (SDS) and biosurfactants from Pseudomonas
      aeruginosa UG2 were utilized at concentrations of 10, 100 and 500 micrograms/g
      soil. Because both surfactants are readily biodegradable, the microcosms received
      a fresh spike of surfactant every 2 weeks. Biodegradation of aged PAH residues
      was monitored by GC/MS for a period of 45 weeks. Results indicated that the
      biodegradation of the three-ring PAH was rapid and almost complete but was slowed
      by the addition of 100 micrograms/g and 500 micrograms/g chemical surfactant.
      Similarly, at the same concentrations, the two surfactants significantly
      decreased the biodegradation rate of the four-ring PAH. In this case, the
      inhibition was more pronounced with SDS. High-molecular-mass PAH (more than four
      rings) were not biodegraded under the test conditions. It was suggested that the
      preferential utilization of surfactants by PAH degraders was responsible for the
      inhibition observed in the biodegradation of the hydrocarbons. The high
      biodegradability and the inhibitory effect of these two surfactants would have a
      significant impact on the development of both above-ground and in situ site
      reclamation processes.

PMID- 9008895
TI  - Two-step degradation of pyrene by white-rot fungi and soil microorganisms.
AB  - The effect of soil microorganisms on mineralization of 14C-labelled pyrene by
      white-rot fungi in solid-state fermentation was investigated. Two strains of
      white-rot fungi, Dichomitus squalens and a Pleurotus sp., were tested. The fungi
      were incubated on milled wheat straw contaminated with [14C]pyrene for 15 weeks.
      CO2 and 14CO2 liberated from the cultures were determined weekly. To study the
      effect of soil microorganisms on respiration and [14C]pyrene mineralization in
      different periods of fungal development, the fungal substrate was covered with
      soil at different times of incubation (after 0, 1, 3, 5, 7, 9 or 11 weeks). The
      two fungi showed contrasting ecological behaviour in competition with the soil
      microflora. Pleurotus sp. was highly resistant to microbial attack and had the
      ability to penetrate the soil. D. squalens was less competitive and did not
      colonize the soil. The resistance of the fungus was dependent on the duration of
      fungal preincubation. Mineralization of [14C]pyrene by mixed cultures of D.
      squalens and soil microorganisms was higher than by the fungus or the soil
      microflora alone when soil was added after 3 weeks of incubation or later. With
      Pleurotus sp., the mineralization of [14C]pyrene was enhanced by the soil
      microflora irrespective of the time of soil application. With D. squalens, which
      in pure culture mineralized less [14C]pyrene than did Pleurotus sp., the increase
      of [14C]pyrene mineralization caused by soil application was higher than with
      Pleurotus sp.

PMID- 9008896
TI  - Biodehalogenation of low concentrations of 1,3-dichloropropanol by mono- and
      mixed cultures of bacteria.
AB  - The degradation of low concentrations of 1,3-dichloro-2-propanol (1,3-DCP) and
      related halohydrins by whole cells and cell-free extracts of soil bacteria has
      been investigated. Three bacteria (strains A1, A2, A4), isolated from the same
      soil sample, were distinguished on the basis of cell morphology, growth kinetics
      and haloalcohol dehalogenase profiles. Strain A1, probably an Agrobacterium sp.,
      dehalogenated 1,3-DCP with the highest specific activity (0.33 U mg protein-1)
      and also had the highest affinity for 1,3-DCP (Km, 0.1 mM). Non-growing cells of
      this bacterium dehalogenated low concentrations of 1,3-DCP with a first-order
      rate constant (kl) of 1.13 h-1. The presence of a non-dehalogenating bacterium,
      strain G1 (tentatively identified as Pseudomonas mesophilius), did not enhance
      the dehalogenation rate of low 1,3-DCP concentrations. However, the mixed-species
      consortium of strains A1 and G1 had greater stability than the mono-species
      culture at DCP concentrations above 1.0 gl-1.

PMID- 9008897
TI  - [Melatonin and biological rhythms: various aspects in human physiopathology].
AB  - Melatonin (N-Acetyl-5-methoxytryptamine) is a hormone secreted mainly by the
      pineal gland or epiphyse and in smaller amounts by the retina. It is
      biosynthesized from tryptophan, the two critical enzymatic steps depend upon N
      Acetyl-transferase (NAT) and 5-hydroxyindole-O-methyltransferase (5-HIOMT). The
      circadian rhythm of melatonin is the same in man and all the laboratory animals
      studied until now with noctural plasma concentrations 3-10 times greater than
      during daytime. The secretion and release of melatonin depend upon a large number
      of exogenous and endogenous factors as e.g. sex, age, pubertal stage, menstrual
      cycle, drugs, season... Light is the major regulating factor which acts through
      the retino-hypothalamic tract. Melatonin is considered as a transducer of the
      light signal forwarding to the organism the information about day length
      (relative length of day and night). It is a time-clue provider used by the
      organism to adapt itself to its environment.

PMID- 9008898
TI  - [Quantification and studies of in vitro toxicity of chemicals extracted from
      synthetic ion exchange media].
AB  - Soluble chemicals extracted from chromatographic media can contaminate pure
      biological preparations. These contaminants that may come from the chemical
      synthesis of the polymers could have adverse effects as far as their toxicity is
      concerned. Ion exchangers made using classical acrylic monomers have been
      investigated for the presence of traces of monomers which are not converted into
      polymers. In vitro toxicity investigations have also been performed with the same
      monomers. Obtained data demonstrated that the amount of free residual monomers
      was below the sensitivity of the analytical methods (HPLC) for both the main
      monomers (acidic and alkaline) and the acrylic bifunctional monomer. Toxicity
      trials showed no adverse effects on human cells in culture. Moreover no
      polyploidia induction was evidenced in cells cultured in the presence of
      monomers.

PMID- 9008899
TI  - [Inactivity of imipramine in the forced swimming test on old mice or on young
      mice undergone chronic glycinergic treatment].
AB  - Balb-C old (10 or 12 months) mice were submitted to the forced swimming test
      (FST) after treatment by imipramine (IMI) or by glycinergic A agonists (which
      operate on the strychnine sensitive receptors). The latter, but not IMI,
      exhibited an anti-immobility effect, predicting an antidepressive activity, in
      the FST. The same results were obtained with young mice (4 months) having
      undergone, 48 hours before the administration of IMI or N-linoleyl glycine
      (glycinergic A) or D-cycloserine (glycinergic B), a chronic (7 days) glycinergic
      A or B (acting on the strychnine insensitive receptors) treatment. These results
      could confirm the recent theories on the anti-NMDA effects of acutely or
      chronically administered IMI and could raise some interesting questions about the
      possible antidepressive activity of glycinergic A agonists.

PMID- 9008900
TI  - [Bioavailability and bone toxicity of barium chloride by chronic administration
      in rats].
AB  - Knowing long term total parenteral nutrition (TPN) can bring 12 micrograms/kg/day
      as barium contamination, we investigated the barium ability to give the same bone
      toxicity as observed in patients' underlying TPN. A preliminary study carried out
      on 21 rats allowed us to calculate the bioavailability of barium chloride (50%)
      with doses fixed at 1 mg/kg for the intravenous route and 10 mg/kg for the oral
      route. As it is very difficult to feed rats parenterally for more than 30 days,
      we decided to give barium chloride orally. Twenty rats received 48
      micrograms/kg/day barium chloride during 4 months. The barium plasma and bone
      levels were not statistically different between the control group and the tested
      group. The femurs and tibias were removed for analysis, carried out by different
      fixation and coloration techniques. No anomalies could be detected in the treated
      group concerning main bone parameters that are disturbed in patients' underlying
      TPN.

PMID- 9008901
TI  - [Pharmacological modulation of mitochondrial oxidative phosphorylation:
      inhibition by cyclosporine A, restoration by trimetazidine].
AB  - When applied to a suspension of isolated mitochondria extracted from rat
      hepatocytes, cyclosporine A decreases ATP synthesis and induces Ca2+
      accumulation. Both effects are considered as possible determinants, even partly,
      of renal toxicity observed with this drug. Trimetazidine antagonizes both effects
      at concentrations easily reached in man with therapeutic dosages. It is concluded
      that the association of both drugs may improve the renal tolerance of
      Cyclosporine A.

PMID- 9008902
TI  - [Synthesis and antiparasitic activity of new N-alkyl derivatives of 1
      (nitrophenyl)-3-(methyl-3-indolyl)-prop-2-ene-1-ones (nitroindolylchalcones)].

PMID- 9008903
TI  - Screening of in vitro antibacterial activity from Syzygium Guineense (Willd)
      hydrosoluble dry extract.
AB  - Diarrhoea is one of the most important causes of infant mortality in the world.
      As modern drugs are expensive or unavailable in developing countries, many people
      use traditional medicines in Africa for the treatment of several diseases. In our
      study, we investigated the antibacterial activity of Syzygium Guineense extract
      in order to assess its activity on some bacterial strains involved in diarrhoeal
      diseases and to justify its use. The aqueous dry extract was prepared by
      decoction followed by evaporating to dryness and tested according to dilution
      method. This extract showed an antibacterial activity against some bacterial
      strains: Salmonella E., Shigella D., Shigella F., E. Coli., Enterobacter A. It
      did not show any activity against Citrobacter F., Proteus M., Klebsiella P.
      Storage conditions (27 degrees C, glass flask) did not affect antibacterial
      properties of the extract.

PMID- 9008904
TI  - [Polyphenolic composition of the leaf of bilberry].
AB  - Dried leaves of 14 harvested batches and one batch from commercial origine of
      Vaccinium myrtillus L present a similar polyphenolic pattern. The mean levels of
      the harvested batches and the levels of the commercial batch were respectively:
      total polyphenol compounds 12.98 and 10.62%, tannins 7.84 and 7.43%, total
      flavonoid compounds 2.98 and 2.20% (spectrophotometry), 1.41 and 1.16% (HPLC),
      quercetin 3-glucuronide 1.02 and 0.83%, hyperoside 0.22 and 0.16%, chlorogenic
      acid 3.66 and 1.58%. The levels were higher in young leaves and lower in old
      leaves. A specific chromatographic profile of the flavonoid compounds and a
      determination method of the tannin or the total polyphenol content were proposed
      in a standardization purpose.

PMID- 9008905
TI  - [Generic drugs and substitution rights: Pandora's box?].

PMID- 9008906
TI  - [Left bundle branch block analysis by body surface mapping. Comparison with
      electrocardiographic and vectocardiographic findings].
AB  - PURPOSE: To compare the correlation between the departure areas (DA), negative or
      positive, in patients whose electrocardiogram showed left bundle branch block
      (LBBB) and association with left ventricular hipertrophy (LVH) and myocardial
      infarction (MI), to the electrocardiographic (ECG) and vectocardiographic (VCG)
      classic criteria. METHODS: The study was carried out with 46 patients (27 males)
      with LBBB. These patients had hypertension (19.5%), coronary heart disease
      (34.7%) and 21 patients with no heart disease (45.8%). RESULTS: The statistic
      analysis using the Cluster method divided the patients in two groups. Group I (22
      patients) showed an average rate for the DA (-2 SD) of 1091 for QRS and of 640
      for ST-T. For the DA (+2 SD), the average rate was 618 for QRS and 881 for ST-T;
      group II (24 patients) showed an averaged for the DA (-2 SD) of 1063 for QRS and
      of 225 for ST-T. For the DA (+2 SD), the averaged rate was 428 for QRS and 600
      for ST-T. CONCLUSION: In general the current ECG/VCG findings, can not
      differentiate the presence of the association of LBBB to LVH and MI. The DA of ST
      T, mainly negative was the most efficient to separate the two groups and help in
      the differential diagnosis.

PMID- 9008907
TI  - [Frequency of utilization and reasons for exclusion from thrombolytic therapy in
      patients with acute myocardial infarction in Salvador-Bahia].
AB  - PURPOSE: To determine the rate of utilization and reasons for exclusion from
      thrombolytic therapy in acute myocardial infarction (AMI) in the setting of
      Intensive Care Unit (ICU) Salvador-BA. METHODS: Retrospective cohort study
      recording patients admitted with suspected AMI in six ICU in Salvador-BA between
      January/93 and December/94 were reviewed. RESULTS: Three hundred and eighty-eight
      of confirmed cases of AMI were analysed, 165 (42.0%) were admitted at public
      hospitals and 225 (58.0%) at private hospitals. Thrombolytic therapy was
      indicated in 143 (36.8%) patients. The thrombolysis was more frequently performed
      in men (PR = 1.96 IC 95% 1.39-2.77), in patients less than 60 years of age (PR =
      4.46 CI 95% 2.17-9.19) and in those with Killip class I (PR = 2.62 CI 95% 1.60
      4.31). The major reasons for excluding from thrombolytic therapy were late
      arrival, old age and lack of ST elevation. Thirty three percent of patients were
      excluded for more than one reasons. Multivariate analysis showed that female
      gender was associated with a reduced indication for thrombolytic therapy,
      independent of the clinical findings on admission. CONCLUSION: The frequency of
      the use and reasons for excluding patients from thrombolytic therapy in AMI in
      Salvador-BA were similar to those of other clinical studies. The recent
      recommendations of the Thrombolysis Brazilian Consensus will enhance the
      utilization of this therapy, as it expands its utilization to elderly patients
      and to those who arrive late to the hospital.

PMID- 9008908
TI  - [Lipid profile changes during the late follow-up after heart transplantation].
AB  - PURPOSE: The aim of this study was to determine the lipid profile after heart
      transplantation. METHODS: We performed sequential analyses in serum (in mg/dL) of
      total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol and
      triglycerides in patients who underwent orthotopic heart transplantation. These
      analyses were performed at one month (33 patients), six months (32), one year
      (26), two years (22) and three years (19) after the transplantation. RESULTS:
      After the heart transplantation there was a progressive elevation in the serum
      levels of total cholesterol (215 +/- 53 at the 1st month, 229 +/- 57 at the 6th
      month, 239 +/- 52 at the 1st year, 250 +/- 53 at the 2nd year and 278 +/- 63 at
      the 3rd year, p = 0.0006). LDL-cholesterol (137 +/- 46 at the 1st month, 152 +/-
      47 at the 6th month, 156 +/- 45 at the 1st year, 164 +/- 43 at the 2nd year and
      180 +/- 58 at the 3rd year, p = 0.03). VLDL-cholesterol (35 +/- 15 at the 1st
      month, 37 +/- 14 at the 6th month, 42 +/- 14 at the 1st year, 42 +/- 15 at the
      2nd year and 45 +/- 17 at the 3rd year, p = 0.01) and triglycerides (169 +/- 75
      at the 1st month, 188 +/- 75 at the 6th month, 216 +/- 70 at the 1st year, 218 +/
      89 at the 2nd year and 255 +/- 103 at the 3rd year, p = 0.001). There were no
      changes in HDL-cholesterol levels (44 +/- 15 at the 1st month, 41 +/- 12 at the
      6th month, 40 +/- 12 at the 1st year, 44 +/- 14 at the 2nd year and 45 +/- 15 at
      the 3rd year, p = ns). CONCLUSION: We observed a progressive elevation in the
      levels of total cholesterol, LDL, VLDL and triglicerides during the 1st three
      years after heart transplantation.

PMID- 9008909
TI  - [Percutaneous mitral valvuloplasty with the single balloon technique. Short-term
      results, complications and in-hospital follow-up].
AB  - PURPOSE: To study the short-term results, complication and in-hospital follow-up
      of 268 percutaneous mitral balloon valvuloplasty (PMBV) procedures performed with
      the low-profile monofoil balloon (LPMB) technique from 1990 to 1995. METHODS: A
      single 30mm balloon diameter was used in 247 (92.9%) procedures, a single 25mm
      balloon diameter in 9 (3.3%), a single 25mm balloon followed by a single 30mm
      balloon diameter in 7 (2.6%) and in 5 procedures a balloon was not used. The mean
      age group was 36 +/- 12 years. Two hundred nineteen (81.7%) procedures were
      performed in women (mean age 36 +/- 12 years) and 49 (18.3%) in men (mean age, 35
      +/- 14 years) (p = 0.78). Patients were in functional class II (NYHA) in 39
      (14.5%), class III in 198 (73.9%) and class IV in 31 (11.6%). Patients were in
      sinus rhythm in 228 (85.1%) procedures and in atrial fibrillation in 40 (14.9%).
      The echocardiographic score ranged from 4 to 14 (mean 7.2 +/- 1.5). RESULTS:
      There were 256 complete procedures, 249 of which were successful (mitral valve
      area (MVA) > or = 1.5cm2 after PMBV). Echocardiographic calculated MVA before
      PMBV was 0.9 +/- 0.2cm2. Hemodynamic calculated MVA before PMBV was 0.9 +/-
      0.2cm2 and after was 2.0 +/- 0.4cm2 (p < 0.000001). Mean pulmonary artery
      pressure decreased from 40 +/- 15mmHg to 28 +/- 10mmHg (p < 0.000001) and mitral
      mean gradient from 20 +/- 7mmHg to 5 +/- 4mmHg (p < 0.000001). In the 256
      complete procedures mitral valve (MV) was competent in 214 and there was 1+
      mitral regurgitation (MR) in 42. After PMBV, MV was competent in 166 and there
      was 1+ MR in 68, 2+ in 16, 3+ in 5 and 4+ MR in 1. There were complications in 14
      (5.2%) procedures, severe MR in 6 (3 or 4+), stroke in 2 and cardiac tamponade in
      6. Two patients died during emergency cardiac surgery after left ventricular
      perforation and 1 after stroke. CONCLUSION: PMBV with the LPMB was an effective
      procedure with a high success rate and a low rate of complications as the more
      usual double-balloon and Inoue balloon techniques.

PMID- 9008910
TI  - [Mitral valvoplasty by balloon catheter. A method in improvement].

PMID- 9008911
TI  - [Congenital isolated hypoplasia of the right ventricle].
AB  - Two cases of congenital trabecular hypoplasia of the right ventricle are
      reported. In the first, the neonatal diagnosis was missed and the child did well
      until the 13th month of life when a modified Blalock-Taussig shunt was done
      because of increasing cyanosis. Outcome was good until the 4th year of life when
      symptomatic atrioventricular block was detected in an emergency situation. A
      bidirectional Glenn anastomosis and pacemaker implantation were successfully
      carried out after clinical establization and the child is doing well up to now.
      The second case presents the disease with its worst features: severe cyanosis and
      acidosis in the first day of life. A modified Blalock-Taussig shunt was performed
      and death occurred soon after the operation.

PMID- 9008912
TI  - [Supravalvar and valvar aortic stenosis associated with valvar and subvalvar
      pulmonary stenosis. Coexistence of two clinical syndromes].
AB  - A 4 year old patient with congenital rubella syndrome, confirmed serologically,
      presents with neurosensorial deafness and a rare association of cardiac
      anomalies: supravalvar and valvar aortic stenosis and subvalvar pulmonary
      stenosis. Bidimensional echocardiography and angiography confirmed the diagnosis
      and the surgical treatment was successful. Due to the presence of somatic
      characteristics of Williams's syndrome, mental retardation and supraortic
      stenosis, the authors postulate that there is a coexistence of clinical syndromes
      responsible for the malformations of this case. This fact is rare on clinical
      settings, requiring accurate diagnosis and treatment.

PMID- 9008913
TI  - [Anatomo-clinical correlation. Case 2/96 (Instituto do Coracao do Hospital das
      Clinicas-FMUSP)].

PMID- 9008914
TI  - [Experimental methods in the study of endothelial function].

PMID- 9008915
TI  - [Morphological aspects, evolution and prognostic factors in pulmonary atresia
      with intact ventricular septum. Review of the literature and update].

PMID- 9008916
TI  - [Coronary angioplasty in patients with restenosis. Characterization of clinical
      and angiographic profiles, hospital clinical course, and implications for the
      selection of patients].

PMID- 9008917
TI  - [Scientific publication triad].
AB  - Considerations are made about the competitiveness, impactedness and
      internationality as characters required for the scientific publications
      evaluation in Brazil. The relative merits of this judgement system is appraised
      in the face of the Third World realities.

PMID- 9008918
TI  - [Determinants of induced abortion among poor women admitted to hospitals in a
      locality of northeastern Brazil].
AB  - In Brazil, abortion is legally allowed only when it is necessary to save a
      woman's life or when pregnancy has occurred following rape. Despite this law,
      induced abortion is widely carried out. This study presents the findings as to
      the determinants of 2,084 abortions admitted to two major obstetric hospitals in
      Fortaleza, Brazil, between October 1992 and September 1993. Most of these women
      (2,074) have admitted an attempt to terminate pregnancy and 10 women were
      classified as induced abortion cases based on the findings of signs of
      intervention such as cervical laceration, perforation or foreign bodies in the
      vagina or uterus. The study findings indicate that self-administration of
      medicines plays an important role in terminating pregnancy. Among the 2,074 women
      who admitted to terminating the pregnancy 66% reported using misoprostol to
      induce abortion. Misoprostol, a prostaglandin E1 analogue indicated for ulcer
      treatment, has been widely used as an abortifacient by women in Brazil.
      Misoprostol has some uterine effects but it is not effective in inducing
      abortion. Among women who were hospitalized for complications resulting from
      abortion about 59.7% were 20 to 29 years old and 22.6% were aged less than 20.
      The majority of the women (91.6%) were Catholic and only 4.3% were illiterate.
      About 62% of the abortion cases lived alone or did not have a stable partner.
      Most of the women (59.2%) reported less than 2 live births and 11.8% had
      experienced a previous abortion; 61.1% of the women were not using a
      contraceptive method at the time of conception. The main reasons for this were
      "fear of side effects", "did not expect to have sexual intercourse" and "did not
      expect to get pregnant". The authors suggest that the situation of a high rate of
      self-inflicted abortion may be changed by the application of an appropriate
      contraceptive and reproductive health programme.

PMID- 9008919
TI  - [On the hypothesis of cesarean birth rate stabilization in southeastern, Brazil].
AB  - Births in S. Paulo State (Brazil) between 1987 and 1993 were studied to test the
      association between cesarean section rates and the social and economic
      development. The study used both Health Regions and hospitals as units of
      analysis. The cross-sectional study of secondary data adopted as variables:
      cesarean section rates in 1987, 1992 and 1993 by hospital and region; kind of
      provider; link of hospital with medical school; post-neonatal infant mortality
      rate; number of banks per inhabitant; and consumption potential of the regional
      central town per inhabitant. The C-section rates in the period studied were
      around 48% for the State; between 21.3 and 85.5% for the regions; between zero
      and 100% for the hospitals; as for kind of provider, the higher rates were found
      in private hospitals (56% in 1993). Medical school hospitals held stable rates
      throughout the period, around 39%. The multiple linear regression showed that
      banks per inhabitant and consumption potential by inhabitants explained 48% of
      the variation of the regional C-section rates. The stabilization of the State C
      section rates is questioned, since the data shows a shift in the mode of hospital
      rates to higher values. A re-structure of the care delivered to births is
      imperative in S. Paulo State, since cesarean sections, besides being medical
      procedures, have become a consumer good, a symptom of the perverse logic that
      pervades the current organization of the health system.

PMID- 9008920
TI  - [Longitudinal study of the mother and child population in an urban region of
      southern Brazil, 1993: methodological aspects and preliminary results].
AB  - All babies born in the hospitals of the city of Pelotas, Brazil, in 1982 were
      studied soon after delivery and followed up prospectively during the first years
      of their lives. In 1993, this study was repeated with a similar methodology, with
      the aim of assessing eventual changes in the level of maternal and child health.
      All five maternity hospitals in the city were visited daily and the 5,304 babies
      born included in the study. They were weighed and measured, and their gestational
      age was assessed using the Dubowitz method. Their mothers were examined and
      interviewed regarding a large number of risk factors. The mortality of these
      children was studied through the surveillance of all hospitals, cemeteries and
      death registries, and all hospital admissions were also recorded. Two nested case
      control studies were carried out to assess risk factors for mortality and
      hospital morbidity. A systematic sample of 655 children were examined at home at
      one and three months of age, and these infants, as well as another sample of 805
      children including all low-birthweight babies were also examined at the ages of
      six and twelve months. Their psychomotor development was also assessed. Losses to
      follow-up were only 6.6% at twelve months. Relative to the 1982 indicators,
      perinatal mortality fell by about 30% and infant mortality by almost 50%. The
      median duration of breastfeeding increased from 3.1 to 4.0 months. On the other
      hand, there was little change in the prevalences of low birthweight or of length
      for age at twelve months. The article that refers this abstract describes the
      methodology of the study and forthcoming publications will present detailed
      results.

PMID- 9008921
TI  - [Mortality by homicide, the fatal consequences of violence. The case of Mexico,
      1979-1992].
AB  - A study of homicide in the population of Mexico, was undertaken for the purpose
      of discovering the mortality panorama by this cause during 1979-1992. Homicide
      mortality trends were analyzed, as well as the main causes by age and sex. Rate
      by cause and sex were also analyzed using a Poisson Regression model. The
      variables were: age, sex, year, external cause of intentional injuries ICD 9th.
      E960-E969. RESULTS: The total number of deaths due to homicide was 198,485. Each
      day 35 persons die in Mexico as a result of homicide. Men were more affected than
      women with a RR of 10.1 and CI (95%) 14.9-16.0, adjusted for age. The main cause
      56% was homicide by fire-arms and explosives. The high relative risk was for
      those aged from 35 to 39 with an RR of 15.4 CI 14.9-16.0. To the cause assault by
      other and unspecified means, the elderly population has a RR of 21.2 IC 19.7
      22.9. Further research in the area and prevention should make use of a
      multidisciplinary approach in considering the multiple causes and solutions to
      this problem.

PMID- 9008922
TI  - [Hospital productivity in the light of hospital indicators].
AB  - Of all the facilities that are utilized by the health area in order to provide
      care, hospitals are certainly the most favorite whether of the population or of
      health professionals. This is due to the amenities and security offered by the
      concentration of human and technological resources. However, this means high
      costs that should be diluted by increases in productivity and quality. Thus
      quality of management, productivity, staffing, even though scrutinised by other
      researchers, deserve further analysis. This research project aims at bringing to
      light the productivity of hospitals by using hospital indicators such as length
      of stay, bed turnover bed turnover and replacement interval as well as the
      employees per bed ratio.

PMID- 9008923
TI  - [Effect of supplementation with peach palm as source of vitamin A: study with
      rats].
AB  - The effect of supplementation with peach palm (Bactris gasipaes H.B.K.), as an
      alternative source of vit. A, in the regional diet of Manaus, AM, Brazil, in
      which the pulp was cooked and transformed into flour, was studied. The biological
      trial involved rats which were depleted in zinc and vitamin A, followed by
      repletion using the regional diet (RD), RD plus peach palm and RD plus vitamin A.
      The parameters used to determine the utilization of vitamin A were the vitamin A
      concentrations in the liver and plasma, and the growth of the animals. The diet
      was prepared according to the data of Shrimpton and Giugliano for families
      earning less than two legal minimum salaries. Adult post-partum rats were used,
      with six male pups each, which received a diet based on casein washed with 1%
      EDTA, without the addition of zinc or vitamin A for a period of 25 days, for the
      purpose of obtaining newly-weaned animals which were deficient in Zn and Vit.A. A
      control group received a diet also based on casein washed with 1% EDTA, but with
      all the nutrients in the quantities suggested by the Committee on Laboratory
      Animal Diets. The repletion period of the newly-weaned rats was of 30 days and
      the experimental design was entirely randomized with four groups of eight rats
      each. The diet supplementation followed the recommendations of the Committee on
      Laboratory Animal Diets. At the end of the experiment, it was observed that rats
      which consumed the diet based on the regional diet of Manaus supplemented with
      either peach palm or vitamin A showed a significantly greater concentration of
      vitamin A in the liver, 43.3 +/- 6.5 micrograms/g, 42.0 +/- 4.3 micrograms/g,
      respectively in relation to the regional diet, 5.5 +/- 1.1 micrograms/g (p <
      0.05). The amount of zinc present in the regional diet, 10.7 mg per day, was
      bioavailable as determined by the concentration of zinc in the femurs. The
      results suggest that the regional diet of Manaus needs to be supplemented with
      vitamin A to maintain the hepatic reserves, and that such supplementation can be
      accomplished with peach palm, an abundant local commodity.

PMID- 9008924
TI  - [Nutritional status of pre-school children of the semi-arid region of Bahia
      (Brazil): II--Vitamin A deficiency].
AB  - A survey of 754 preschool children was undertaken in the urban areas of seven
      small towns of the semi-arid region of Bahia, Northeastern Brazil, to determine
      the prevalence of vitamin A deficiency, as well as its association with variables
      such as a age, family income, mother's schooling and dietary adequacy in vitamin
      A. Protein energy malnutrition and anemia were also studied and are reported
      separately. The clinical ophthalmological examination did not reveal any signs or
      symptoms of xerophthalmia amongst these children. In 563 children serum retinol
      was determined and the average value found was 20.3 micrograms/dl (SD = 10.8
      micrograms/dl); the prevalence of deficient serum retinol (below 10.0
      micrograms/dl) was of 15.3%. In all 7 localities studied, the prevalence of
      deficient retinol levels was above 5.0%, the criterion recommended by WHO for
      considering it a Public Health Problem. The distribution of serum retinol was
      similar between the sexes, but there was an age trend: the prevalence of
      deficient and low levels decreased with age. There was no association between
      deficient serum retinol and family income per capita or mother's education.
      Results from the 24 h food consumption survey revealed that only 8% of children
      had an adequate intake of vitamin A through the diet; 66% received less than 1/2
      and 35% less than 1/4 of the recommended daily intake of vitamin A. Vitamin A
      deficiency should be considered a Public Health Problem in the region due to the
      high prevalence of deficient levels of serum retinol as well as the large dietary
      inadequacy.

PMID- 9008925
TI  - [Atherosclerotic cardiovascular disease, lipemic disorders, hypertension, obesity
      and diabetes mellitus in the population of a metropolitan area of southeastern
      Brazil. II--Lipemic disorders].
AB  - This study has sought to characterize the prevalence of lipemic disorders and
      other risk factors of atheroschlerotic cardiovascular disease in population
      groups of Cotia county in Greater S. Paulo, Brazil. The population groups were
      defined on the basis of socio-economic characteristics and geographical location
      within the county such as provided elements for the delimitation of the "study
      areas". A sample representative of each of these areas was taken, constituting in
      all 1,041 individuals. The data related to eating habits were collected from a
      sub-sample of 568 people. The lipemic disorders diagnosed were as follows: high
      risk hypercholesterolemias with values approximately 240 mg/dl for total
      cholesterol and approximately 160 mg/dl for LDL-cholesterol; borderline risk
      hypercholesterolemias with values > 200 mg/dl and > 130 mg/dl for total
      cholesterol and LDL-cholesterol respectively; hypertriglyceridemia, with values
      approximately 250 mg/dl. The following risk factors were included: atherogenic
      eating habits (consumption of proteins of animal origin, saturated fats and
      cholesterol), smoking, drinking, sedentary life style, obesity (IMC > 25 kg/m2),
      hypertension (140/90 mmHg) and diabetes mellitus (glycemia > 120 mg/dl). The
      results found were the following: 1--the average number of risk factors was
      significant by greater among men than among women, for the age groups below 50
      years of age (p < 0.01): between 50 and 55 years of age they were equal for the
      two groups, reaching their greatest value at 60 years of age with a sharp
      reduction after this latter age as regard the men but presenting a constant
      gradual increase for the women; 2--the average number of risk factors increased
      with age for both sexes (p < 0.01); 3--the prevalences of high risk
      hypercholesterolemias together with hypertriglyceridemia (> = 250 mg/dl) were
      significantly greater in the classes of higher socio-economic level; 4--the
      lipemic profile associated with lipemic disorders show that these latter rarely
      occur with just one constituent in isolation; 5--when the high-risk
      hypercolesterolemias are added to the borderline cases accompanied by two or more
      risk factors and hypertriglyceridemia they give a total of 39.2% of men and 32.8%
      of women, that is to say, 35.4% of the sample need immediate clinical-educational
      intervention.

PMID- 9008926
TI  - [Intelligent quotient of obese children and adolescents by the Weschler scale].
AB  - The intellectual characteristics of 65 obese children and adolescents (weight for
      height > or = 140%), aged 8 to 13 years and 11 months, were compared to those of
      35 eutrophic children and adolescents (weight for height between 90 and 110%; and
      stature for age > 95%) of the same age group, utilizing the Wechsler Intelligence
      Scale for Children--WISC. Children and adolescents of the two groups were paired
      according to age groups, schooling level and socioeconomic condition. The obese
      group was composed of new patients assisted at the Department of Pediatrics of
      the Federal University of S. Paulo (Escola Paulista de Medicina), Brazil. The
      control group was made up of children from public primary schools, from the same
      geographical area as those studied. The eutrophic group presented significantly
      better performance in the intelligence test (Intelligence Quotient--IQ) than the
      obese group (average IQ--91 x 85; p < 0.05). Eutrophic children and adolescents
      revealed a wider range of interests, better capacity for social adaptability as
      well as greater speed and dexterity. Although weak, there was a positive
      correlation between income level, weight/stature relation (W/S) and IQ. There was
      no correlation between IQ and level of schooling. The eutrophic boys from higher
      income levels showed better perceptual and spacial organizing ability and a wider
      range of interests than those from the lower income groups. In spite of the fact
      that all the average IQ results presented consistently favored the eutrophic in
      relation to the obese, it is not possible to confirm one group's superiority over
      the other, due to the wide range of intervenient factors involved in the
      intelligence process.

PMID- 9008927
TI  - [Strength and will: theoretical and methodological issues from the standpoint of
      risk in epidemiology and HIV/AIDS prevention].
AB  - Health education related to HIV/AIDS prevention is approached from the standpoint
      of risk in epidemiology. The shortcomings of the outcomes of health programs, in
      terms of controlling the spread of the disease led the author to consider the
      premisses that lie behind these programs. One of them is the idea of the
      rationality of the "receiver" of health information. Notions related to public
      understanding of concepts produced by epidemiology are considered. Some
      limitations of epidemiological methods regarding interactive relationships in
      processes of being affected by AIDS are discussed. A method that deals with
      interactional aspects is presented.

PMID- 9008928
TI  - [Rabies virus isolation in insectivorous bat Lasyurus borealis].

PMID- 9008929
TI  - [Occurrence of Aedes scapularis (Diptera:Culicidae) in artificial breeding area
      of southern Brazil].

PMID- 9008930
TI  - [Lung injury in acute pancreatitis. Influence of pancreatic enzymes reduction].
AB  - A previous report has show that cerulein in physiological doses reduces the rate
      mortality of pancreatitis by decreasing the enzyme content of the pancreas.
      Clinically detectable signs of lung injury develop in up to 50-70 percent of
      patients with acute pancreatitis. The aim of the present study was to assess the
      effect of acute reduction of pancreatic enzyme content on the pancreatitis
      pulmonary injury. Experimental haemorrhagic pancreatitis was induced by
      intraductal injection of 5 per cent sodium taurocholate in two groups of Wistar
      rats: group I (pancreatitis) and group II (pancreatitis after decreasing
      pancreatic enzyme content). Dye Evans blue was used to evaluate the lung injury.
      The degree of histologically observed lesions were similar in both groups, but
      the pulmonary lesion was smaller in group II than group I (p < 0.05). IN
      CONCLUSION: 1) pancreatitis' pulmonary lesion may be related with pancreatic
      enzymes that reach the blood stream and 2) the reduction of the pancreatic enzyme
      content has a beneficial effect on acute pancreatitis and reduces its pulmonary
      injury.

PMID- 9008931
TI  - [Perforating eye injuries in children].
AB  - The author studied 140 cases of perforating eye injury in children up to 15 years
      old admitted at the Clinic Hospital of the Medical College of the University of
      Sao Paulo (Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao
      Paulo) from January 1989 to December 1993. These cases represent 24.71% of the
      total of the perforating eye injuries seen during this period, showing a ratio of
      76.42% of males, a ratio of 2/1 in the group from 0 to 6 years old, 7/1 in the
      group from 7 to 11 years old and a ratio of 3/1 in the group from 12 to 15 years
      old. The most common perforating eye injuries were due to sharp objects (54.71%),
      contusion (20%), explosions (7.85%) and flying objects (5.71%). The relation
      between the severity of the injury and the prognosis is emphasized. Safety
      precautions should be effective in order to reduce frequence and morbidity of
      these perforating ocular injuries.

PMID- 9008932
TI  - [Pericarditis in a general hospital].
AB  - The authors studied 57 patients with pericarditis in the Ward of Internal
      Medicine of the University of Sao Paulo from January 1993 through May 1995. A
      comparison was made with the results of a similar study performed in the same
      hospital in 1989. Increasing frequency of pericarditis was verified.
      Tuberculosis, formerly the most frequent etiologic agent, decreased while
      neoplastic diseases became more common.

PMID- 9008933
TI  - [Nutritional assistance to patients during radiotherapy].
AB  - With the aim of assessing the possible benefits of nutritional therapy, 140
      patients were prospectively studied during radiotherapy of the head and neck
      (81%) and esophageal cancer (19%). Mean age was 56.0 (17-80), with 114 males and
      26 females. Duration of both nutrition and radiotherapy was 78.0 +/- 45 days.
      Tube feeding was the primary modality in 50.7% of the population, and oral
      regimens in the remaining 49.3%, but associations between the methods were also
      used. Enteral diets were supplied under the supervision of a specialized tem for
      home alimentation (PROSNED). Compliance to the program was 100%, and a lymphocyte
      count diminished along this period (1933 +/- 1033 vs 1265 +/- 688, p. 0.001). A
      subjective improvement was reported by 84% of the population, and total calorie
      intake, that was below 60% of estimated needs in 100% of the cases initially,
      significantly improved to just 40% inadequate at the end of the observations.
      Radiotherapy was associated with mucositis in 21% of the patients, taste changes
      in 79%, xerostomy in 81%, anorexia in 66% and odinophagia in 59%. In the
      individuals selected for enteral feeding, side-effects were represented by
      technical problems (20%) and gastrointestinal disorders (13%). All patients
      completed the nutritional support program and there was no mortality in this
      series. It is concluded that; 1) Early nutritional support during radiotherapy
      was able to maintain or improve the nutritional status; 2) Tube feeding, alone or
      in combination with oral diets, was indicated whenever appropriate and
      contributed to fulfillment of the energy requirements; 3) Reduction of total
      lymphocytes could not be prevented by the mentioned therapy; 4) Complications of
      enteral alimentation were mild and affected a small proportion of the population;
      5) Troubles induced by radiotherapy were as frequent as expected, and tended to
      disturb the intake of food; 6) The compliance to the therapeutic plan was
      excellent and can be attributed to the efforts of the multidisciplinary team as
      well as to the help of the specialized home alimentation unit (PROSNED): Diet
      therapy. Cancer. Nutritional assessment. Radiotherapy. Nutritional support.

PMID- 9008934
TI  - Hematologic disorders in trauma patients during parenteral alimentation with
      lipids.
AB  - Total parenteral nutrition with lipids is a well-accepted modality of metabolic
      support in seriously ill trauma patients. Intolerance to lipid administration is
      unusual when dosage limits are not exceeded, and few hematologic disturbances
      have been recorded with modern fat emulsions. In the course of intravenous
      alimentation of six adults admitted for traumatic lesions, eosinophilia with or
      without leukocytopenia was noticed after periods of four days to five weeks.
      Principal clinical events and hematologic derangements were documented in this
      population. Sepsis was not always present in the patients by the time of the
      complication, and in those that did require antibiotics and other drugs, the
      prescription remained unchanged along the episode. Discontinuation of the
      nutritional regimen with lipids was followed by normalization of the hematologic
      profile, suggesting that an acute or sub-acute allergic reaction was responsible.
      The appearance of skin rash in two occasions reinforces this hypothesis, and the
      possibility of hemophagocytosis merits consideration in two of the cases who
      displayed reversible acute leukocytopenia. It is concluded that blood cell
      aberrations are possible during intravenous feeding with lipids in trauma
      subjects, but tend to respond to suppression of the lipid-containing nutritional
      prescription.

PMID- 9008935
TI  - [Mesenteric venous thrombosis after azygos-portal disconnection with splenectomy
      for the treatment of bleeding esophageal varices in mansonian schistosomiasis.
      Three cases reports].
AB  - The consequence of an acute mesenteric venous thrombosis following porta-azygos
      disconnection for the treatment of bleeding esophageal varices due to mansonian
      schistosomiasis has not been well defined in the literature. The clinical
      manifestations reported were fever, spasmodic abdominal pain associated with food
      intake. We treated three patients with thrombosis of the portal-mesenteric trunk
      following porta-azygos disconnection and adopted a conservative clinical approach
      in two patients while one had to have a surgical small bowel ressection.

PMID- 9008936
TI  - [Perforating eye injuries caused by motor vehicle accidents: cases assisted
      during the year 1994].
AB  - A prospective study of 32 patients with perforating eye injuries caused by motor
      vehicle accidents, 24.32% of the 131 cases of perforating injuries admitted at
      the University of Sao Paulo Medical School Hospital from January to december,
      1994 was performed. Most of the accidents occurred at night (68.75%), and in
      urban areas (65.63%). There were more male victims (65.63%), mostly under 25
      years of age (53.13%). None of the victims were using seat belts and those in the
      front seats were more vulnerable. Safety precautions should be effectively in use
      in order to reduce frequency and morbidity of these injuries.

PMID- 9008937
TI  - [Mechanisms and evaluation of multiple organ and system failure after trauma].
AB  - Multiple organ failure (MOF) is a major cause of death of ICU trauma patients.
      Despite intensive clinical and experimental investigation, the exact
      physiopathology of this syndrome is unclear. Although diverse cellular and
      humoral mediators have been identified, their mechanistic role is still debated.
      In this article the authors discuss recent results of this investigation. They
      present recently published criteria for MOF quantification, and focus on the
      mechanisms and mediators of MOF syndrome, emphasizing the role of sepsis, the
      intestinal ischemia/reperfusion MOF model, the role of polymorphonuclear
      neutrophil, and the relationship between adult respiratory distress syndrome
      (ARDS) and the development of MOF syndrome.

PMID- 9008938
TI  - [Program evaluation Curriculum of the University of Sao Paulo Medical School. For
      the year 1994 and the period 1989-1994].
AB  - The authors present the results of the Program of Curriculum Evaluation of the
      University of Sao Paulo Medical School for the year of 1994, as well as the 1989
      1994 period. The academic year of 1994 wasn't a good year to the medical
      graduation regarding disciplines from the first to the fourth year; only 14.3% of
      the disciplines achieved 90% or more of "excellent" + "good". The disciplines
      held at internship continued, on the most, doing well. The analysis of the 1989
      1994 period outstands different sequential evaluation.

PMID- 9008939
TI  - [immunization and immune response to pneumococcal vaccination].
AB  - The aim of this work was to define antibody levels against four neumococcal
      serotypes, before and after neumococcal vaccination in patients with respiratory
      infections. Fifty one patients were studied, 19 children from 1 to 5 years old;
      children from 6 to 18 years old and 22 adults from 27 to 65 years old. IgG anti
      neumococcal, antibodies, against weeks after vaccination. There was a significant
      increase in antibody titers against all serotypes in subjects older 7 years. In
      children of less than 6 years, the response to serotype 14 was non significant.
      The intensity of response differed according to the studied serotype and the
      percentage of patients that responded to each serotype increased with age. Five
      patients older than 18 years were identified as non responders to all four
      serotypes. It is concluded that neumococcal vaccine increases anti-neumococcal
      antibodies in patients with recurrent infections and allows the identification of
      patients with specific antibody deficiency syndromes and normal total
      immunoglobulin levels.

PMID- 9008940
TI  - [Immunophenotype. Clinical and laboratory features of acute lymphoblastic
      leukemia in Chile. Study of 500 children and 131 adults].
AB  - We describe the clinical features and immunophenotype of 500 children and 131
      adults with acute lymphoblastic leukemia (ALL), diagnosed between 1984 and 1993.
      Cases were classified, according to immunophenotype in B-cell ALL with three
      subtypes (pro-B or null, common and B) and T-cell ALL. Among children, common ALL
      accounted for 74% of cases and pro-B all was more common in children of less than
      one year (14%). B ALL was observed in 2% of children. Ten percent of children,
      mostly males, had T-cell ALL. The third part of these children had high leukocyte
      counts and a mediastinal mass. Children from Mapuche origin, compared with
      Caucasian children had a lower proportion of common ALL (36 and 74% respectively)
      and a higher proportions of T-cell ALL (41 and 10% respectively). Among adults
      common ALL was the most common phenotype (72%) followed by T-cell ALL (15%), pro
      B ALL (11%) and B-cell ALL (2%). There was a lower incidence of children with
      common ALL with positive cytoplasmic immunoglobulin compared to North American or
      European studies (2 and 15-33% respectively) and a higher proportion of adults
      with common ALL compared with pro-B cell ALL, in contrast to European studies
      that show a higher proportion of patients with pro-B cell ALL. No other
      immunophenotypic, clinical or laboratory differences were observed with ALL from
      developed countries. It is concluded that the immunophenotyping of ALL allows a
      more precise diagnosis of this disease.

PMID- 9008941
TI  - [Somatosensory evoked potentials and symptomatic response to dopaminergic drugs
      in Parkinson's disease].
AB  - Short latency somatosensory evoked potentials were measured in 10 patients with
      Parkinson's disease before and after the administration of Apomorphine 5 mg sc.
      Eight of these subjects were reassessed after one month of treatment with Levo
      Dopa. These potentials were measured in other nine subjects before and after one
      month of treatment with Selegiline 10 mg od. There was a significant increase of
      frontal potential N30 in nine of 10 subjects that received apomorphine, in seven
      of eight patients treated with Levo-dopa and seven of nine patients treated with
      Selegiline. No changes in N20 parietal potential were observed. During
      apomorphine test, changes in N30 potential preceded clinical improvement in six
      patients and occurred simultaneously in three patients. No changes with
      apomorphine in N30 potential were observed in two healthy males. There was no
      relationship between electrophysiological changes and duration of disease or
      motor fluctuations. It is concluded that short latency somatosensory evoked
      potentials are an objective means of measuring dopaminergic response in patients
      with Parkinson's disease.

PMID- 9008942
TI  - [Breast cancer: comparison between biochemical and immunohistochemical
      determination of estrogen receptors].
AB  - Immunohistochemical (IH) assessment of nuclear estrogen receptor has been
      considered an alternative method to conventional biochemical assay. The present
      work intends to compare specificity and sensitivity of IH and biochemical
      technique to assess nuclear estrogen receptor in formalin-fixed and paraffin
      embedded mammary carcinoma samples. IH positive reaction was defined as 14% or
      more nuclear staining in 100 cells counted under high magnification (400x).
      Biochemical assay was considered positive over 10 fmol/mg of protein. 66 cases
      were collected with a mean age of 55.6 years and a mean tumor size of 25.2 mm.
      Histologically, 62 cases were ductal carcinomas, 2 lobular carcinomas, and 2
      medullary carcinomas. Biochemical assay for estrogen receptor was positive in 35
      cases (63%) and IH in 40 cases (71%). The present results show that IH assessment
      of estrogen receptor is highly specific and sensitive. Estrogen receptor present
      in non-tumor cells and blood vessels walls may disclose false positive
      biochemical results and false negative result if the tumor mass is small or there
      are isolated tumor cells. IH assessment of estrogen receptor can be performed in
      small samples, including in situ lesions. The method of fast, reliable, and of
      lower cost, IH may be considered the method of choice in cases with insufficient
      sample for biochemical assay and/or in tumors containing scant cells.

PMID- 9008943
TI  - [Polydactyly: a genetic epidemiological study in Santiago, Chile].
AB  - The aim of this work was to study the prevalence at birth and family aggregation
      of polydactyly in Chile. We studied 125,652 newborns between 1969 and 1991. The
      prevalence was 1,329 for each 1,000 live newborns and higher in males than in
      females. Familial recurrence was 22.5% and gene penetrance was estimated as 0.5
      for the postaxial-A type and 0.3 for the postaxial-B type. Gene penetrance for
      postaxial-B type was higher in males. Estimation of gene frequencies and mutation
      rates gave the highest values for postaxial-B polydactyly.

PMID- 9008944
TI  - [Usefulness of adenosine deaminase determination in cerebrospinal fluid for the
      diagnosis of meningeal tuberculosis: 4 years experience at a public hospital].
AB  - The aim of this work was to study the usefulness of CSF adenosine deaminase
      determination in the diagnosis of tuberculous meningitis and determine if the
      proposed cutoff value of 7.1 i.u./ml had the better sensitivity and specificity.
      We retrospectively studied 148 patients, 12 with tuberculous meningitis and 136
      with other central nervous system diseases. Adenosine deaminase values ranged
      from 3.6 to 31.2 i.u./ml in patients with tuberculous meningitis and from 0.1 to
      312 i.u./ml in controls. The best sensitivity/specificity ratio (83.3 and 85.3%
      respectively) was obtained using a cutoff value of 6.5 i.u./ml. It is concluded
      that CSF adenosine deaminase values are useful in the diagnosis of tuberculous
      meningitis and that the cutoff value should be lowered to 6.5 i.u./ml to improve
      its diagnostic yield.

PMID- 9008945
TI  - [Clinical usefulness of Multitest in the evaluation of cellular immunity].
AB  - The aim of this work was to assess cellular immunity using the Multitest CMI and
      relate its results with lymphocyte counts and lymphocyte subpopulations
      determined using monoclonal antibodies against CD4 and CD8 and fluorescence
      microscopy. We studied 51 patients (31 male), 20 infected with HIV, 18 recurring
      infections, 5 with cancer, 2 with tuberculosis and 6 with miscellaneous
      diagnoses. According to Multitest results, patients were classified as normal,
      hypoergic or anergic. Twenty five percent of patients were normal, 65% hypoergic
      and 10% anergic. Eighty percent of anergic patients were infected with HIV. No
      differences in total lymphocyte count were observed between the three groups. CD4
      lymphocyte count was lower in anergic patients when compared with the other two
      groups. All patients with CD4 counts below 200 cells/mm3 were anergic. It is
      concluded that Multitest CMI is useful for the assessment of cellular immunity
      and complements the determination of lymphocyte subpopulations.

PMID- 9008946
TI  - [Lawsuits against physicians in Chile].
AB  - Lawsuits against are becoming relevant in Chile. We analyzed 18 trials against
      physicians that occurred between 1977 and 1985 and that were ruled by
      Metropolitan Region courts. The causes of demands were death of patients in 8
      trials and severe lesions in the rest. Twelve trials originated from surgical
      procedures (six from gynecological interventions), and nine came from private
      clinics. Nine trials lasted less than two years and three, more than 5 years.
      Sentence was pronounced by criminal courts in 12 cases and by appealing courts in
      six.

PMID- 9008947
TI  - [Measurement of total serum IgE by enzyme immunoassay with three commercial
      reagents].
AB  - We measured total serum IgE in 14 patients with allergic diseases and 16 healthy
      subjects, using three commercial ELISA kits. The correlation of results among the
      three kits was analyzed using Passing and Bablock regression parameters. Results
      show that measurements of the different kits do not coincide. One kit shows
      differences using sera from normal subjects. There is no correlation among kits
      when using sera from allergic patients. It is concluded that it is not possible
      to determine exactly the amount of IgE using these kits, specially in subjects
      with elevated levels.

PMID- 9008948
TI  - [Nocardiosis in a renal transplant recipient].
AB  - We report a unilateral pulmonary nocardiosis in a 51 years old male that received
      a renal allograft. The clinical picture appeared 68 days after transplantation
      and the culture of a bronchoalveolar lavage showed the presence of Nocardia
      asteroides. Cyclos-porine and azathioprine were discontinued and trimethoprim
      sulphamethoxazole was started with a good clinical response. Afterwards,
      azathioprine was restarted and the patient is asymptomatic at the present moment.

PMID- 9008949
TI  - [Portal vein thrombosis associated with essential thrombocytosis. Clinical cases
      and review of the literature].
AB  - Lately, myeloprolipherative disorders are frequently reported as causes of portal
      vein thrombosis, probably due to the early detection of latent cases of this
      condition. We report two patients with portal vein thrombosis that presented with
      abdominal pain, nausea, vomiting and clinical consequences of portal hypertension
      such as variceal hemorrhage, splenomegaly and ascites. Diagnosis was made by a
      CAT scan in one patient and doppler ultrasound in the other. Both patients had
      high platelet counts and an essential thrombocytosis in the bone marrow.

PMID- 9008950
TI  - [Systemic leptospirosis as a cause of multiple organ failure. Report of a case].
AB  - Leptospirosis is a world-spread zoonosis that is incidentally acquired by humans.
      It causes a diphasic febrile illness in which the Weil syndrome is its severest
      form, with renal, hepatic, clotting and central nervous system involvement. We
      report a 73 years old male, that was admitted to an intensive care unit with
      multiple organ failure due to leptospirosis. The clinical picture initially
      resembled a sepsis due to biliary tract obstruction and was operated, not finding
      a biliary tract obstruction. Considering the history of a fall to sewed waters,
      leptospirosis was suspected and treatment with penicillin was started, obtaining
      a full recovery of the patient.

PMID- 9008951
TI  - [Hepatitis A vaccination. Opinion of the Chilean Infectology Society].
AB  - Hepatitis A is endemic in Chile with rates of 100 cases per 100,000
      inhabitants/years, figure that triplicates in school age children. Its social
      impact justifies educational and other public work measures to control it.
      Vaccines are an effective but expensive control resource. The vaccine elaborated
      with the inactive HM 175 strain, recently licensed in Chile, is immunogenic,
      effective and well tolerated in adults and children over 3 years old. Its main
      indication is for voyagers to endemic areas and patients with chronic liver
      diseases. In Chile, its individual prescription requires the assessment of
      patient's individual risk and basal immunological status. Its massive application
      requires a better knowledge of hepatitis A geographical distribution, age of
      infection and cost benefit ratios.

PMID- 9008952
TI  - [Cardiology of yesterday, today and tomorrow].
AB  - The subject of this lecture has been chosen in relation to the contribution that
      Professor H Alessandri made in the first half of this century, as an outstanding
      clinician in the professional, humanistic and ethical development of generations
      of physicians in this country. This lecture is divided in three sections: the
      first reviews the practice of cardiology in the 50's, a period of initiation of
      the present advances in the specialty, still dominated at that time by a
      semiologic and clinical approach. The second part presents examples of the
      significant contributions made by newer technologies in the fields of
      echocardiography, nuclear medicine, electrophysiology and therapeutic procedures.
      Finally, an assessment is made of the needed balance between technology and
      clinical judgement, coupled with humanistic and ethical considerations in the
      management of patients.

PMID- 9008953
TI  - [Manipulation of genes causing diseases].
AB  - The intervention on specific genes causing diseases in mammals as in humans is
      nowadays feasible. Technology has allowed the expression of a correct gene
      introduced to a cell or to inhibit the expression of an undesirable gene. This
      opens therapeutic possibilities for a great assortment of diseases, from genetic
      errors of metabolism to AIDS. The assays performed have been scarce, mainly due
      to fears on possible collateral effects. The National Institutes of Health has
      required to present the protocol for analysis and approval to a committee of 20
      people, for every proposal of clinical trial. Only 100 clinical trials in
      catastrophic or incurable diseases have been approved. Up to now, the rate of
      complications has been low and the approval of a greater amount of clinical
      trials is expected in the near future.

PMID- 9008954
TI  - [What, how much and when the university student drinks].
AB  - The aim of this work was to define the epidemiological profile of alcohol
      ingestion and its associated risks, in university students. A social survey about
      drinking habits was performed to a random sample of 528 students, aged 17 to 26
      years old, 54% male, from Austral University. Eighty two percent of males and 79%
      of females drink alcoholic beverages. They mainly consume beer and strong
      spirits. Their main consumption is occasional, during parties or celebrations.
      Thirty percent of males and 15% of females had three or more inebriations during
      the last year. Nine percent of males and 3% of females can be considered as
      problem drinkers. Student that drink alcohol have lower grades that teetotalers.
      It is concluded that alcohol consumption is frequent among students.

PMID- 9008955
TI  - [Homage to professor Dr. Ignacio Matte Blanco (1908-1995)].

PMID- 9008956
TI  - [Epizootics of pasteurellosis in a semi-intensive breeding farm of indigenous
      rabbits in Senegal].
AB  - Epizootic pasteurellosis appeared in a semi-intensive breeding farm (200 animals)
      of indigenous rabbits in Thies (ENSA), Senegal, during the 1995 wet season
      (August to October). It provoked death in 87 animals. Young animals were
      particularly sensitive to the disease. Nasal discharge, conjunctivitis, eye loss
      and otitis media and interna were observed in young rabbits while posterior
      paresis was noted in mature rabbits. Pasteurella multocida, Klebsiella pneumoniae
      and Pseudomonas aerogenes were identified. An antibiogram revealed the germs were
      sensitive to chloramphenicol, sulfamethoxazole/trimethoprim and colistin. High
      temperatures and humidity during the wet season may have contributed to the
      outbreak of the disease from healthy carriers introduced at the founding of the
      farm. Colistin and chloramphenicol treatments were administered before
      vaccinating all rabbits against pasteurellosis.

PMID- 9008957
TI  - [Preliminary epidemiological survey on prevalences of Salmonella spp. at Bissau
      abattoir (Guinea-Bissau)].
AB  - Considering the importance of Salmonella as a mortality and morbidity agent, in
      particular in children, a study on Salmonella prevalence was performed in
      collaboration with the Guinea-Bissau authorities through an epidemiological
      survey at Bissau slaughterhouse. The prevalence rate in 117 bovines slaughtered
      and approved for human consumption was 13.7%, with 8.5% sampled in the intestine
      and 5.1% in the gallbladder. Rectal swabbing in 74 live animals resulted in the
      isolation of S. stanleyville only. On the other hand, no strain was found in
      hepatic lymph nodes. These strains, some of them pathogenic for humans, are
      mostly called "exotic": S. bargny, S. brazzaville, S. virchow, S. rubislaw, S.
      brazil, S. calabar, S. havana, S. hull, S. marseille, S. shipely, S. uppsala, S.
      114, 12;l,w;e,n,x. A new serotype is described: S. 28:f,m,t:-. Isolated from the
      caecal content, it had MSHA fimbriae (+ + + +) and 7.0 Log 10 as DL 50. Most of
      these strains presented simple or multiple antibiotic resistance. They were more
      frequently isolated during the wet season than during the dry season.

PMID- 9008958
TI  - First reported isolation of Mycoplasma bovis from an outbreak of bovine mastitis
      in Sudan.
AB  - Thirty-seven isolates of Mycoplasma bovis were recovered from 42 milk samples
      from imported Friesian cows in Khartoum State. This is the first report on
      isolation of M. bovis in the Sudan.

PMID- 9008959
TI  - Outbreak of infectious bursal disease associated with acute septicaemic
      colibacillosis in adult prelayer hens.
AB  - An outbreak of infectious bursal disease (IBD) occurred concurrently with acute
      septicaemic colibacillosis in 15 week old prelayer hens. The septicaemia was
      preceded by a subclinical IBD. Mortality in the outbreak began with lesions of
      septicaemia and Escherichia coli was isolated from the heart blood of the birds.
      After antibiotic treatment of the bacteraemia, mortality continued, spiked,
      declined and then ceased. IBD was confirmed by bursal lesions characterized by
      severe lymphocytolysis and cystic degeneration of the lymphoid follicles. Out of
      253 birds, 42 (16.60%) died within eight days. The circumstances of the outbreak
      suggested that lack of IBD booster vaccination favoured the establishment of
      subclinical IBD, which suppressed immunity to predispose the birds to
      colisepticaemia.

PMID- 9008960
TI  - In vivo and in vitro characterization of two camelpoxvirus isolates with
      decreased virulence.
AB  - Two camelpoxvirus (CPV) strains isolated from camels with generalized skin
      disease were serially passaged on Vero cells. Various phenotypic properties were
      investigated in vitro and in vivo and compared with those of the corresponding
      wildtype strains. In many aspects no differences were observed. However, in a
      mouse model both passaged strains proved to be highly attenuated. In addition,
      both strains failed to replicate in a cell line derived from camel skin cells.
      Comparison of physical maps established for enzymes HindIII and Xhol revealed
      deletions accounting for a total of 22 kbp in one attenuated strain. In the
      second strain only minor alterations were noted.

PMID- 9008961
TI  - [Integrated control of tropical parasitic diseases in animals].
AB  - In the past, parasite control in domestic animals has relied mainly on the use of
      drugs and pesticides. Although these compounds are still of great importance in
      the prevention and treatment of parasitic diseases, in recent years the emphasis
      has shifted to a more flexible approach, integrating various other control
      measures. The main reasons for this change are:--development of parasite
      resistance to the compounds used; --reduced development of new compounds to
      overcome resistance (increasingly more stringent regulations on toxicity and
      residues, resulting in very high research and development costs, insufficient
      return for industry because of the short life-span of new products due to
      resistance and because the market for compounds in developing countries is
      limited and poor);--increasing cost of new products for consumers;--problems
      associated with toxicity, environmental pollution and residues in animal
      products. Integrated parasite management makes use, where possible, of biological
      and mechanical control, of acquired and innate host resistance, and genetical,
      ecological, sanitary and regulatory procedures, although chemical control can
      seldom be entirely eliminated. Cost-effectiveness and sustainability in all
      respects are of primary importance.

PMID- 9008962
TI  - [Value of an antiparasitic treatment against Strongyloidea and Coccidia in
      Djallonke ewes at lambing].
AB  - Three groups of 14 Djallonke ewes each have been compared: group E received one
      antiparasitic treatment with Ivermectin, or Valbazen and Amprol at lambing, group
      T2 received three classical antiparasitic treatments with the same drugs
      according to the seasons (at the beginning and at the end of the long rainy
      season, and at the end of the short rainy season) group T1 remained untreated.
      The onset of sexual activity occurred 71.5 +/- 5.4 days (lot E), 74.5 +/- 6.3
      (lot T2) and 104.3 +/- 10.3 (lot T1) after lambing. So, intervals between
      lambings were 255.7 +/- 11.8 (lot E), 245.9 +/- 13.5 (lot T2) and 298.2 +/- 24
      (lot T1). Lambing other characteristics were almost the same in the three groups:
      prolificacy 127-137%, weight at birth 1.2-1.4 kg, daily weight gains (0-90 days)
      99-114 g and mortality 39-48%. It seems economically more profitable to treat
      against internal parasites once at lambing rather than three times a year
      according to the seasons.

PMID- 9008963
TI  - Osteoid osteoma of the carpus. Case reports and a review of the literature.
AB  - Osteoid osteoma mainly affects long bones, and is rarely observed at the hand.
      The authors report three cases of osteoid osteoma in the carpus (one case in the
      scaphoid, one in the triquetral, one in the capitate), treated by removal of the
      entire nidus. No bone grafting or intercarpal arthrodesis was necessary. There
      were no recurrences.

PMID- 9008964
TI  - Peripheral gangrene in African children: a clinical report of twelve cases.
AB  - Clinical observations of 12 cases of peripheral gangrene in children are
      reported. All patients presented with ischemia of one or more limbs without any
      history of trauma, vascular injury or snake bite. Prior to their admission, all
      these children had received some form of traditional "African" therapy. By means
      of exclusion severe vasospasm secondary to the traditional treatment was
      considered the causative factor of the peripheral gangrene in all the children.
      Surgical exploration of the arteries with a Fogarty embolectomy catheter in two
      patients and medical treatment in six patients was attempted. The overall results
      were disappointing, with most resulting in incapacitating amputations.

PMID- 9008965
TI  - Late superior gluteal nerve palsy following posterior fracture-dislocation of the
      hip.
AB  - An unusual case of late superior gluteal nerve palsy complicating posterior
      fracture-dislocation of the hip is reported. Posterior fracture-dislocation of
      the hip was Grade V according to the classification of Thompson and Epstein, and
      Type IV according to the subclassification of Pipkin. The palsy resulted from
      traction by scar tissue formation. Excision of the scar tissue and decompression
      of the superior gluteal nerve led to complete recovery.

PMID- 9008966
TI  - Iatrogenic posterior interosseous nerve palsy following an elbow fracture.
AB  - Posterior interosseous nerve palsy following elbow surgery is not uncommon.
      Nevertheless, precise etiology of the palsy is rarely described in the
      literature. In this paper the possible causes of the posterior interosseous nerve
      palsy are reviewed and an uncommon iatrogenic lesion after surgical treatment of
      an elbow fracture is reported.

PMID- 9008967
TI  - Metastatic lesion of the cervical spine secondary to an extraocular sebaceous
      carcinoma.
AB  - A case of cervical spine metastasis from an extraocular sebaceous carcinoma of
      the scalp is presented. Anterior decompression and fusion were performed and
      resulted in complete relief of symptoms. Postoperatively the primary tumor
      behaved in a very aggressive manner, with visceral metastases leading to the
      death of the patient in a few weeks.

PMID- 9008968
TI  - Compartment syndrome associated with an osteocartilaginous exostosis.
AB  - The authors describe a compartment syndrome of the deep posterior flexor
      compartment due to perforation of the popliteal artery by an osteocartilaginous
      exostosis, in a healthy 13-year-old boy. The difficulties in making the diagnosis
      are discussed. In a review of the literature regarding this condition, the
      combination of compartment syndrome and exostoses could not be found.

PMID- 9008969
TI  - Bilateral stage III osteonecrosis of the femoral head treated with core
      decompression. Case report and review of the literature.
AB  - A case report of a 17-year-old girl with Ficat stage III osteonecrosis of the
      femoral head, secondary to treatment with corticosteroids for Crohn's disease, is
      presented. Core decompression, mainly performed because of the intense pain,
      traction and long-term partial weight bearing led to a good result, clinically as
      well as radiologically.

PMID- 9008970
TI  - Implant failure four years after resection and reconstruction of a femur for a
      chondrosarcoma.
AB  - The authors describe an original reconstruction technique following resection for
      a chondrosarcoma of the femur. Although fatigue failure of the implant occurred
      four years later, they still think that this surgical procedure may be considered
      as a good treatment option in patients with a limited life expectancy.

PMID- 9008971
TI  - Urodynamic evaluation of urinary incontinence following radical prostatectomy:
      our experience.
AB  - Thirty-four patients after retropubic radical prostatectomy, were evaluated with
      urodynamic studies. Patients were divided in three groups depending on the degree
      of urinary continence. A statistically significant difference was found between
      different groups for the mean functional profile length and maximal urethral
      closure pressure. Detrusor instability was detected in 11 patients with moderate
      incontinence and in 1 patient with severe incontinence. Neither differences of
      age, previous prostatic surgery, tumour extension, nor preservation of the
      neurovascular bundles had any significant influence on recovery of continence.

PMID- 9008972
TI  - Laparoscopic ureterolysis in retroperitoneal fibrosis.
AB  - We reported on 5 patients with retroperitoneal fibrosis with dilatation of the
      upper urinary tract. All patients were operated on laparoscopically. Surgery
      consisted of complete ascending ureterolysis from the pelvis up to the renal
      pelvis, biopsy of periureteral tissue, intraperitonealisation and/or preparing an
      omental flap to separate the ureters from the retroperitoneal vessels. Operating
      time was reduced from 4 hours in a unilateral case down to 5 hours in a bilateral
      case by performing three-dimensional video endoscopy. In case of Ormond's disease
      postoperative immunosuppressive medication was given. Ureterolysis in Ormond's
      disease is a rare but reasonable indication for reconstructive laparoscopic
      surgery. Both ureters are accessible in full length either transperitoneal or
      retroperitoneal. Provided all goals of open surgery can be achieved by the
      laparoscopic technique, patients will benefit from the minimal access.

PMID- 9008973
TI  - Obstructive urinary retention in a young female: case report.
AB  - The authors report a case of acute urinary retention in a young female patient
      with a large uterine leiomyoma. Urinary symptoms resolved completely after
      surgery.

PMID- 9008974
TI  - Ureteral stump metastasis from renal adenocarcinoma: case report and literature
      review.
AB  - The occurrence of metastasis along the ureteral stump after previous radical
      nephrectomy for renal adenocarcinoma is very rare, only 47 cases having been
      reported in the literature. We present a case of metastasis of renal
      adenocarcinoma, occurring in the ureteral remnant, more than three years after
      ipsilateral radical nephrectomy. The analysis of this and previously reported
      cases leads us to propose radical nephro-ureterectomy as treatment of choice in
      certain cases of renal adenocarcinoma, instead of radical nephrectomy alone,
      notably when preoperative urine-cytology shows the presence of adenocarcinoma
      cells, and/or when vascular tumor infiltration is present. This adjuvant surgical
      step is of course only justified in those cases where a reasonable life
      expectancy is present at the time of diagnosis, and thus especially applicable in
      the smaller T2 tumor group.

PMID- 9008975
TI  - Dumbbell stone of prostatic fossa after prostatectomy. A combined ESWL and
      suprapubic percutaneous treatment.
AB  - We report our experience with a combined treatment of extracorporeal shock wave
      lithotripsy and percutaneous suprapubic lithotripsy for a dumbbell-shaped stone
      of prostatic fossa associated with multiple bladder calculi, in the same
      operative session. Because of the successful result, we believe the association
      of the two treatments for this complex calculus to be an easy, effective and
      minimally invasive method. ESWL should be considered for the primary management
      of these rare calculi, suprapubic percutaneous endoscopy can be helpful in rapid
      and complete removal of fragments.

PMID- 9008976
TI  - A local sphincter-saving treatment of distal rectal cancer.
AB  - For the last years less radical approaches to management of distal rectal cancers
      have been sought to decrease the morbidity of standard surgical therapy. The
      results in 34 patients selected for local conservative treatment are discussed,
      with an analysis of complications and recurrences in the follow up. The real play
      off is not simply the extension of life, but also improvement in its quality,
      mainly in terms of sphincter functionality. New protocols, integrating local
      conservative surgery and neo adjuvant radio and chemo-therapy, can attain a
      future improvement of the results.

PMID- 9008977
TI  - Microsurgery and changes in the testicular and epididymal production of
      spermatozoa.
AB  - The researchers studied a group of azoospermic patients with obstructions of the
      seminal canals and a group of oligoasthenospermic patients suffering from
      varicocele in order to analyze the factors that influence the success of surgery
      aimed at recovering fertility. In the 46 patients suffering from obstructions of
      the deferent duct and the extremity of the epididymis, the time factor proved
      decisive if the obstruction lasted longer than 6 years: in this case, damage to
      the seminiferous tubules is not reversible. With obstructions dating back less
      than 4 years, the causes and the location of the obstruction are more incisive.
      Success was achieved in 100% of vasectomy cases and in 37.5% of epididymal
      deferential anastomoses. In research literature, the superiority of microsurgery
      for treating these types of pathologies is taken for granted. In patients
      affected by oligoasthenospermia the effectiveness of laparoscopic ligation of the
      spermatic veins was compared to that of the Belgrano I technique. Of the 30
      patients with bilateral varicocele and oligoasthenospermia dating back less than
      4 years, 73.3% of the 15 patients operated on using the Belgrano 1 technique
      experienced sperm normalization; in the 15 cases operated on using laparoscopic
      ligation of the spermatic canals, normalization was much less frequent. Seventy
      five percent of another group of 40 patients whose infertility did not have a
      duration of longer than 4 years and were operated on using microsurgery
      techniques were normalized. The percentage of the 60 oligoasthenospermic patients
      for longer than 6 years normalized was 16.6%.

PMID- 9008978
TI  - Physiological responses of men and women during exercise in hot environments with
      equivalent WBGT.
AB  - Eight Japanese men and women participated in this study. They were randomly
      exposed to two environments: hot-dry; HD (Ta = 40 degrees C, rh 30%, wet bulb
      globe temperature (WBGT) = 32 degrees C) and hot-wet; HW (Ta = 31 degrees C, rh =
      80%, WBGT = 32 degrees C) for 110 min. During the exposure, they rested on a
      bicycle ergometer for 20 min during rest and 30 min during recovery, then they
      pedaled it with an intensity of 40% VO2 max for 60 min. Tre, Tsk, and HR were
      recorded every minute. Total sweat loss and dripping were measured by independent
      bed balances which was connected to a computer processing with an accuracy of 1 g
      throughout the experiment. Sweat sodium concentration at forearm and back sites
      were collected by sweat capsule technique. These results showed that delta Tre,
      Tsk, evaporated sweat, dripping sweat, body heat storage of both sexes in HD were
      significantly higher than these in HW during exercise. HR of men in HD at the end
      of recovery was slightly higher than that of women. Whereas the sweat sodium
      concentration at forearm and back sites in both sexes remained unchanged either
      in HD or HW environment, it was found that HD was more stressful than HW
      environment under equivalent WBGT.

PMID- 9008979
TI  - Contribution of peripheral chemoreceptor drive in exercise hyperpnea in humans.
AB  - The peripheral chemoreceptors play a dominant role in the respiratory
      compensation of lactic acidosis during heavy exercise of humans. Our object was
      to determine the contribution of peripheral chemoreceptors to exercise hyperpnea
      during mild to moderate and heavy exercise above the anaerobic threshold. We used
      a hyperoxic suppression test in six normal male subjects. Inspired gas was
      abruptly changed without the subject's knowledge from air to pure oxygen for 5 to
      6 breaths. The maximal ventilatory depression after O2 breathing was 5.5 +/- 1.7
      L/min (BTPS) at mild exercise, and the depression increased with increasing
      exercise intensity up to 12.8 +/- 4.1 L/min (BTPS). The relative contribution of
      the peripheral chemoreceptors to ventilation in terms of percentage of the
      maximal ventilatory depression was maintained, being 20% throughout the entire
      work ranges studied. The contribution of the peripheral chemoreceptors to total
      ventilation is hardly altered by lactic acidosis caused by heavy exercise above
      the anaerobic threshold according to our data. These results suggested that the
      peripheral chemoreceptors may not be solely responsible for excessive
      hyperventilation, or residual activities of peripheral chemoreceptors still exist
      after O2 breathing especially during heavy exercise above the anaerobic
      threshold.

PMID- 9008980
TI  - Cardiorespiratory responses to cycling exercise in trained and untrained healthy
      elderly: with special reference to the lactate threshold.
AB  - The fastest growing age group in the United States and Japan is the elderly.
      There is a need to develop appropriate exercise training guidelines designed
      specifically for healthy older persons. Recent reports have shown that the
      lactate threshold (LT) can be used to evaluate the clinical significance of
      aerobic power (VO2max) and its effect of exercise training in the elderly.
      However, there is a lack of research comparing the LT between well-trained and
      sedentary elderly individuals. Also, the effect of exercise training on the heart
      rate (HR) at LT needs further investigation. The purpose of this study was to
      compare the LT levels between the older trained men (T group; n = 72, age = 71.3
      +/- 5.8 yr, range 60-85 yr) and apparently healthy but untrained elderly men (U
      group; n = 172, age = 72.2 +/- 5.7 yr, range 60-93 yr). The LT was measured
      during an incremental cycle ergometer test. A low relationship was found between
      VO2 corresponding to LT (VO2LT) and age in the T (r = 0.20, P < 0.05) and U
      groups (r = 0.43, P < 0.05). A significant difference was found in the VO2LT
      between the T and U groups. The absolute VO2LT corresponded to approximately 6
      and 4 METs for the T and U subjects, respectively. However, there was no
      significant difference in HR corresponding to LT (HRLT) between the two groups
      (T; 109 +/- 19 b.min-1, U; 107 +/- 13 b.min-1). The data show that the absolute
      VO2LT is higher for T than U elderly subjects and is associated with a HR of
      approximately 108 b.min-1 for both groups. Recommended exercise intensity in
      terms of HR may not differ between trained and untrained elderly men.

PMID- 9008981
TI  - Is endurance performance of handgrip exercise influenced by the two different
      clothing ensembles?
AB  - The purpose of this study was to investigate the effects of wearing two different
      clothing ensembles on endurance performance of handgrip exercise in eight female
      subjects in the climatic chamber (25 +/- 1 degrees C, 50 +/- 10% RH). The
      experimental clothing ensembles were HALF and LONG. The clothing ensemble HALF
      consisted of half-sleeved shirts, knee-length trousers and sandals; LONG of long
      sleeved shirts, long-trousers, socks and walking shoes. The subjects carried out
      the preliminary exercise for 1 hr as scheduled which was composed of slow running
      on the horizontal treadmill for 25 min, rest for 10 min and running again for 25
      min the same as the first running. After the preliminary exercise, the subject
      exercised with a hand ergometer lifting a weight of 15% of maximal voluntary
      contraction at the rate of 35 contractions per min until volitional exhaustion.
      Rectal temperature, skin temperatures, heart rate, body weight loss, clothing
      microclimate, number of contractions were measured during the experiment and
      compared between two clothing ensembles. An important result was that the
      endurance performance of handgrip exercise was significantly greater in HALF than
      in LONG, for which the lower maintenance of core temperature and mean skin
      temperature in HALF during the 1 hr preliminary exercise might be responsible.
      Our present and former results indicate a significant participation of clothing
      for the endurance performance of handgrip exercise.

PMID- 9008982
TI  - Effects of chicken extract on the recovery from fatigue caused by mental
      workload.
AB  - Folk wisdom suggests that chicken extract is useful for recovery from physical
      and mental fatigue. To explore this question, the physiological effect of Brand's
      Essence of Chicken (BEC), a popular chicken extract used as a traditional remedy,
      was assessed during recovering from mental stress. We quantitated the blood
      levels of stress-related substances, and examined the task performance and
      subjects' mood states during mental workloads. Subjects were 20, healthy male
      students who have never tasted BEC. They took two bottles of BEC or a placebo (70
      ml/bottle) daily in the morning for 7 days. On the final experimental day, two
      mental workload tests were performed: (A) a mental arithmetic test (MAT; 1600
      trials of two or three figure-addition or subtraction for 40 min). (B) a short
      term memory test (SMT; 20 trials of memorizing 9 digit numbers). Blood was
      collected before and after each workload task. After the mental workload, the
      recovery of mean cortisol level of subjects who consumed BEC was significantly
      faster than that for those consuming the placebo. The task performance of
      subjects performing the MAT and SMT was also improved with BEC consumption
      compared with placebo. According to the profile of mood state questionnaire,
      subjects felt more active and less fatigued during the workload when they took
      BEC regularly. We conclude that the extract of chicken has the potential to
      metabolize stress-related substance in blood and to promote recovery from mental
      fatigue.

PMID- 9008983
TI  - Discrimination of forearm's motions by surface EMG signals using neural network.
AB  - We tried to discriminate different forearm's motions by surface EMG signals using
      neural network. In order to get a higher discrimination rate, the positions of
      electrodes were improved. We also tried to discriminate similar motions in order
      to clarify the limitation of the discrimination by surface EMG signals. Two
      experiments were carried out. One was to discriminate five different motions:
      grasp, wrist flexion, wrist extension, forearm pronation, and forearm supination
      (Experiment 1). The other was to discriminate four similar motions which have
      different quantitative definitions at grasp, wrist flexion/ extension, or forearm
      pronation/supination (Experiment 2). Four surface electrodes were placed on the
      skin above the main active muscles: short radial extensor m. of wrist, supinator
      m., long radial extensor m. of wrist, and ulnar flexor m. of wrist, considering
      anatomical functions of the forearm's muscles. EMG signals were recorded during 2
      sec while the subjects kept the motions. Recorded EMG signals were sampled at 200
      msec intervals after full-wave rectifying and low-pass filtering. Therefore, the
      number of sampling data patterns of EMG signals was 10 for every motion. Three
      layers of neural network was used for discrimination. The number of units in the
      input layer is 4, and the number of units in the output layer is 5 or 4. In order
      to get the best discrimination rate of the motions, we changed the number of
      units in the hidden layer from 3 to 12. The neural network was trained by the
      back-propagation algorithm. In Experiment 1, the best average values of
      discrimination rates under three patterns of EMG signals for each subject were
      96.0%, 98.0%, and 87.2% when the numbers of units in the hidden layer were 10,
      11, and 3 respectively. In Experiment 2 using original EMG patterns, the best
      average values of discrimination rates at grasp, extension/flexion, and
      pronation/supination were 59.5%, 76.0%, and 25.0% respectively. By using
      normalized EMG patterns, these were 40.0%, 84.8%, and 55.5% respectively.

PMID- 9008984
TI  - What about clinical judgment?

PMID- 9008985
TI  - Emerging technologies and professional development.

PMID- 9008986
TI  - Charlena M Seymour.

PMID- 9008987
TI  - Treatment outcomes data for adults in health care environments. Task Force on
      Treatment Outcomes and Cost Effectiveness.

PMID- 9008988
TI  - Ethics and the Internet.

PMID- 9008989
TI  - How effective is the Lee Silverman voice treatment?

PMID- 9008990
TI  - Burning mouth syndrome: patient management.
AB  - Burning mouth syndrome is an underdiagnosed and often poorly managed oral sensory
      disturbance. This paper discusses the recognition of the condition and suggests
      clinical approaches to ensure a correct diagnosis and appropriate management. The
      expansion of the traditional dental role of the dentist is reviewed in the
      context of overall oral and general health particularly with respect to the
      syndrome which demands an intensive work-up, open discussions with the patient,
      and a carefully planned long-term management strategy.

PMID- 9008991
TI  - Methadone and caries. Case reports.
AB  - Several cases of advanced tooth destruction from widespread severe carious
      lesions are presented where methadone syrup has been used intra-orally in a drug
      rehabilitation programme. Aetiological factors are discussed and suggestions made
      concerning treatment plans and social implications for these patients.

PMID- 9008992
TI  - Mental paraesthesia: an ominous symptom. Case reports.
AB  - The sudden onset of paraesthesia in the distribution of the mental nerve should
      be regarded as an ominous symptom. It is usually related to events such as
      fractures or dentoalveolar surgery, but in the absence of such history this
      finding should be regarded with suspicion. Four case studies are presented in
      which the patient presented with unexplained mental paraesthesia, which were
      later related to metastatic malignant disease. Careful medical history is
      required to alert the clinician to appropriate diagnostic procedures and ensure
      correct management.

PMID- 9008993
TI  - The use of low-tack chewing gum for individuals wearing orthodontic appliances.
AB  - A clinical study was carried out to determine the acceptability of a sugar-free,
      low-tack chewing gum by orthodontic patients undergoing fixed appliance
      treatment. Twenty-five orthodontic and 25 non-orthodontic control subjects were
      questioned on their preference between regular-tack and low-tack chewing gum. The
      orthodontic subjects showed a strong preference for the low-tack gum compared
      with the regular-tack gum. It was concluded that low-tack, sugar-free chewing gum
      can be used by orthodontic patients to increase saliva flow, with the potential
      to promote remineralization and help reduce white spot lesion formation related
      to fixed orthodontic appliances. This gum should also be of value in patients
      being treated for xerostomia who are wearing a partial denture.

PMID- 9008994
TI  - Efficacy of arthroscopic surgery and midlaser treatments for chronic
      temporomandibular joint articular disc derangement following motor vehicle
      accident.
AB  - As a result of motor vehicle accident soft-tissue injury, temporomandibular joint
      articular disc derangement may develop and persist despite symptomatic treatment
      and medication. This study reports the effectiveness of management directed at
      controlling the TMJ and masticatory neuromuscular pain dysfunction with a
      TMJ/interocclusal stabilization appliance, specific biofeedback and ultrasound
      therapy. Following these conservative measures residual articular disc
      derangement was present in some subjects who were offered arthroscopic surgery
      and infrared midlaser with TMJ/occlusal stabilization. Twenty subjects with
      residual disc derangement were randomly selected into two groups with and without
      arthroscopic surgery, and analyses of variance made before treatment, 12 months
      after conservative procedures, 3 months following arthroscopic surgery and
      midlaser therapy and 3 years since commencement of management. Dependent
      variables compared were pain-discomfort, Clinical Dysfunction Index, articular
      disc derangement and maximal voluntary jaw opening. Conservative management alone
      provided significant reduction of pain-discomfort and clinical dysfunction, while
      arthroscopic surgery resulted in significant reduction in articular disc
      derangement. The midlaser with TMJ/occlusal stabilization maintained significant
      improvement in the variables (p < 0.01) for both groups. The common articular
      deviations in form found at arthroscopy were soft tissue alteration with
      hyperaemia, synovitis, synovial membrane and posterior attachment folding with
      connective tissue hyperplasia, and disc displacement with fibrous adhesions. The
      Global Status Score of pain behaviour compared with residual function, confirmed
      the presence of greater pain before treatment commenced.

PMID- 9008995
TI  - An in vitro study of the distribution of silver and fluoride following
      application of 40 per cent silver fluoride solution to dentine.
AB  - An in vitro test system involving application of 40 per cent silver fluoride
      solution to prepared cavities of moderate depth in extracted teeth failed to
      demonstrate the passage of significant amounts of fluoride into the dental pulp,
      despite a very high concentration of fluoride (100,000 ppm) in the applied
      solution. The test system used may not be conducive to quantitative investigation
      of ionic transfer because of disruptions to pulp circulation and fluid flow
      through dentine following tooth extraction. For this reason, the results are
      inconclusive as to whether or not application of 40 per cent silver fluoride as a
      cavity varnish of liner and its use in the 'atraumatic' technique for treating
      deep caries, can be considered safe clinical procedures.

PMID- 9008996
TI  - Adhesion to enamel of light-cured poly-acid dental materials.
AB  - The purpose of this study was to determine the tensile bond strengths of a resin
      modified glass ionomer cement and a poly-acid modified resin composite to enamel.
      Three different enamel surface preparations (unetched enamel; enamel treated with
      10 per cent polyacrylic acid, enamel etched with 35 per cent phosphoric acid),
      were used. On etched enamel, the glass ionomer cement (15.0 MPa) and the resin
      composite (14.3 MPa) had significantly higher bond strengths than the other
      groups tested, but were not significantly different from each other. In the acid
      treated groups, cohesive failure within the material occurred in all specimens,
      while in the other groups, all specimens failed adhesively. Further investigation
      is required to test the clinical efficacy of these restorative materials.

PMID- 9008997
TI  - A laboratory study of dimensional changes for three elastomeric impression
      materials using custom and stock trays.
AB  - Clinical success of fixed prosthodontic procedures is dependent in part upon the
      dimensional accuracy of elastomeric impression materials and impression
      procedures. Three elastomeric impression materials were used in custom and stock
      trays to determine the accuracy of impressions taken from an experimental
      stainless steel model representing premolar and molar bridge abutment
      preparations. Horizontal and vertical individual abutment and interabutment
      dimensions were measured on die stone replicas, and the measurements compared
      with those obtained from stainless steel master models. The results of this study
      demonstrate polysulphide is the least accurate impression material for both
      vertical and horizontal individual abutment dimensions. However, for
      interabutment horizontal dimensions, no statistical differences were noted
      between impression material types when using a custom tray. Stock trays produced
      unreliable results for all the materials tested.

PMID- 9008998
TI  - Provision of orthodontic care to adolescents in South Australia: the type, the
      provider, and the place of treatment.
AB  - There are many pathways involving different providers and locations that
      individuals may take in obtaining, orthodontic services. The aim of this study
      was to document the provision of orthodontic services and establish the pathways
      taken toward fixed orthodontic treatment by adolescents in South Australia. Data
      were collected on the use of orthodontic services by a cohort of adolescents
      enrolled in the School Dental Service at age 13 years and again at age 15 years.
      By age 15 years, 83.2 per cent of the adolescents had received orthodontic
      consultations, 27.3 per cent had received fixed orthodontic treatment and 41.4
      per cent had received other forms of orthodontic treatment (extractions, space
      retainers or removable appliances). The majority of fixed orthodontic treatment
      was supplied by orthodontists in the private sector, while extractions and
      removable appliances were provided mainly by public sector general dentists. Most
      individuals used services in both the public and private sectors and the most
      frequent pathway taken by the adolescents receiving fixed orthodontic treatment
      involved consultation in both the public and private sectors, non-fixed
      orthodontic treatment in the public sector and fixed orthodontic treatment in the
      private sector. The findings indicate wide access to orthodontic consultation and
      a high uptake of fixed orthodontic treatment once the adolescent sought private
      sector orthodontic consultation. Orthodontic care was seen to be an interactive
      process between public sector general dentists and private sector orthodontists.

PMID- 9008999
TI  - The times, they are a changing.

PMID- 9009000
TI  - Ross River virus and Barmah Forest virus infection. Commonly asked questions.
AB  - Ross River virus infection and Barmah Forest virus infection are two commonly
      reported arboviral diseases in Australia. Ross River virus has long been
      recognised as a cause of epidemic polyarthritis and polyarticular disease.
      Clinical disease as a result of Barmah Forest virus infection has only been
      identified since 1988 and Australia is the only country in which this virus has
      been detected. Severe and prolonged symptoms can occur as a result of infection
      with either virus and may result in significant distress to the patient. This
      article reviews some of the issues that patients raise in relation to both Ross
      River virus and Barmah Forest virus disease including the source of infection,
      the duration of symptoms and measures to prevent infection.

PMID- 9009001
TI  - Sterilisation. Past confusions and current recommendations.
AB  - Since 1990 more than 15 reference texts and guidelines from various bodies and
      organisations have been produced to assist or direct medical practitioners in
      their understanding of sterilisation and/or disinfection issues. Approximately
      90% of these monographs is a rewrite of standard thoughts and approximately 10%
      represent new thoughts, often in contradiction to opinions published previously.
      As a result, much confusion exists. The most recent offering is that from the
      National Health and Medical Research Council titled Infection Control in the
      Health Care Setting. The stated aim of this publication is to 'establish a
      nationally accepted minimum standard for infection control'. Although an
      excellent document in many ways, it too adds to the confusion. This article
      reviews this document and places its recommendations into perspective with other
      authoritative works. A summary of what is now appropriate for general
      practitioners to do in their own clinical settings is also provided.

PMID- 9009002
TI  - The management of common ocular infections.
AB  - Bacterial and viral infections involving the anterior segment of the eye and
      ocular adnexa present commonly in general practice, affecting patients of all
      ages. Careful assessment of the patient is necessary to distinguish between
      benign conditions and those with more serious complications. An understanding of
      the microbiology and pathogenesis of these conditions is helpful in rationalising
      current therapeutic approaches. This article focuses on the clinical presentation
      of common infections of the lids, conjunctiva and cornea, with a discussion of
      relevant therapeutic regimens for each condition.

PMID- 9009003
TI  - Tick-borne diseases in Australia.
AB  - Tick bites are a common problem in Australia and an important cause of morbidity
      in medical and veterinary practice. Complications include local inflammation and
      infection, paralysis and transmission of various pathogens. Over the past three
      decades, several new tick-borne diseases have been recognised both in Australia
      and overseas. The importance of these diseases has also increased, in part due to
      greater recreational activities occurring in tick infested areas. However, our
      understanding of the microbiology and epidemiology of many of these diseases is
      incomplete.

PMID- 9009004
TI  - Is there a postinfection fatigue syndrome?
AB  - Prolonged fatigue syndromes are common in general practice. Most of these
      syndromes are secondary to other common medical or psychological disorders. It
      appears, however, that some specific infectious illnesses are associated with
      prolonged recovery. Theories as to the mechanisms for such post infection fatigue
      syndromes include a range of immunological, psychological and neurobiological
      processes. Current evidence suggests disruption of fundamental central nervous
      system mechanisms, such as the sleep-wake cycle and the hypothalamic-pituitary
      adrenal axis, may underpin the clinical features of this disorder. Treatment
      should focus on the provision of continuous medical care, physical rehabilitation
      and adjunctive psychological therapies.

PMID- 9009005
TI  - Sports medicine. Shoulder pain. Part III: Shoulder instability.

PMID- 9009006
TI  - Wound management. Sixty five year old man with right leg ulcer.

PMID- 9009007
TI  - Clinical incidents in general practice. Keeping on track with test results.
AB  - The incident Monitoring in General Practice Project began as an initiative of the
      Professional Indemnity Review. Anonymous data from general practitioners about
      unintended and possibly adverse events were collected in order to develop
      preventive strategies that might ultimately increase patient safety and therefore
      reduce litigation. Feedback and sharing of experiences and ideas about these
      events, possible management strategies or about the project as a whole are
      invited from readers.

PMID- 9009008
TI  - Practice tip. W-plasty for ragged lacerations.

PMID- 9009009
TI  - Infectious diseases case study. Could this be viral?

PMID- 9009010
TI  - A pathological cause for aggression.
AB  - A case of insulinoma is presented which highlights the need for the physician to
      be alert and non-judgmental, and the importance of performing basic, simple and
      appropriate investigations. In this case a fasting blood glucose provided the
      evidence for the diagnosis.

PMID- 9009011
TI  - Team games.

PMID- 9009013
TI  - Harnessing and controlling the information deluge.
AB  - A number of information management tools are available to assist the general
      practitioner to cope more readily with the deluge of information presented to
      them. These tools can also enable the practitioner to seek out relevant pieces of
      information in a timely fashion to assist with patient care.

PMID- 9009014
TI  - Use of computers by general practitioners for patient education.
AB  - The need for patient education in general practice is increasing due to patient
      expectations and the changing nature of general practice. Computers have the
      potential to enhance the interaction between general practitioners and their
      patients and can enable patient education to be carried out efficiently and
      effectively. A number of computerised patient education tools are already
      available for use in general practice. The role of the Internet in patient
      education may also prove to be important.

PMID- 9009015
TI  - The legal acceptability of an electronic medical record.
AB  - The acceptability of an electronic medical record in a court presents a challenge
      to the legal system which has yet to be met. A definitive solution must straddle
      the boundaries of the disciplines of law, medicine and information technology.
      This paper discusses the law as it relates to evidence, information security as
      it applies to assuring the integrity of an electronic record, and solutions for
      the GP. While a definitive answer to the problem of legal acceptability of
      electronic medical records is not offered, the issues are explored in order to
      stimulate discussion among the relevant disciplines, for only through the
      cooperation of experts in these fields can a solution ultimately be found.

PMID- 9009016
TI  - Registers, recalls and reminders.
AB  - General practitioners care for a large number of patients who require a wide
      range of preventive care procedures. Most patients attend at least once each
      year, providing an opportunity to offer and/or perform indicated preventive care.
      If these opportunities are taken, only a few patients will ever need to be
      recalled for preventive care. Reliable, thorough and consistent opportunistic
      offering of preventive care depends on having an efficient information system
      that reminds the doctor of what care is due. Manual systems are too expensive to
      use for this task because of their high labour costs. Recalling all patients
      routinely for preventive care is inefficient, expensive and unrewarding.
      Electronic medical record systems can remind doctors of when preventive
      interventions are due and generate recall notices at the lowest cost.

PMID- 9009017
TI  - Transferring electronic medical records.
AB  - This article outlines the variety of computing environments, application systems
      and data structures that are available to the general practitioner. The transfer
      of data from and to electronic medical records systems will become more important
      as their use increases. Transferability requires the ability to match the data
      elements between the conversing application systems, and carry out a series of
      communication steps. Ways to ensure data element matching are described. The
      communications steps are delineated, and methods of achieving these steps briefly
      explained. The transfer methods proposed by the medical software industry of
      Australia are dealt with in detail. They involve the creation of an industry
      standard 'meta-record' which acts as a standard interface or gateway to the real
      record. The communication steps are carried out by a medical record 'agent',
      which is created and maintained by an independent organisation.

PMID- 9009018
TI  - Planning practice-based clinical teaching: Part I.
AB  - Among the many roles clinicians are expected to perform is that of educator of
      junior colleagues. However, most clinicians have received little or no
      developmental instruction for this role. Furthermore, the nature of medical
      education is changing, and the skills required of new graduates are being
      refocused. This series of three articles presents a guide to some of the
      philosophical and educational issues at the heart of current changes in medical
      education. As well as developing an argument for making practice-based clinical
      teaching student-centred and problem-orientated, suggestions for planning and
      implementing teaching which utilise these approaches are outlined. In this first
      article the changing nature of clinical teaching is discussed and the educational
      principles of problem-based and student-centred learning are defined. The second
      article looks at the steps involved in planning a clinical teaching session. The
      third and final article looks at the development and implementation of teaching
      sessions.

PMID- 9009019
TI  - The Royal Flying Doctor Service. The South Australian operation (central section)
      -past and present.
AB  - The history of the Royal Flying Doctor Service (RFDS)--the South Australian
      operation--is traced from its humble beginning in 1955 as part of a group general
      practice in Port Augusta to an aero-medical service in South Australia and
      involving general practitioners, nurses and retrieval specialists (trauma,
      medical emergencies, neonatology and obstetrics).

PMID- 9009020
TI  - Epilepsy and the art of F M Dostoevsky.

PMID- 9009021
TI  - Chest pain of spinal origin.

PMID- 9009023
TI  - Restructuring of general practice will lead to shortage of rural locums.

PMID- 9009022
TI  - Regional nerve blocks.

PMID- 9009025
TI  - Australian immunisation campaign.

PMID- 9009024
TI  - Serotonin reaction and its treatment.

PMID- 9009026
TI  - Asthma.

PMID- 9009027
TI  - Pap smear reports: time for another change?

PMID- 9009028
TI  - Do patients with asthma fill their prescriptions? A primary compliance study.
AB  - OBJECTIVE: To examine primary noncompliance in patients suffering with asthma.
      METHOD: A prospective matching of prescriptions written and then dispensed for
      patients with asthma. The subjects were patients who were given a general
      practitioner's prescription for asthma during a 3 month period (1993) in an
      isolated rural setting. RESULTS: During the period of the study, participating
      GPs documented 359 prescriptions and of these only 251 (70%) were dispensed by
      the pharmacies. Primary noncompliance was therefore 30%. The relative risk (RR)
      of mild asthmatics not filling their prescriptions is 0.81 (95% CI; 0.771 < RR <
      0.92) when compared to severe asthma. Compared to patients of high socioeconomic
      status; patients of low and medium socioeconomic status have decreased relative
      odds of filling their prescriptions, that is, RR = 0.84 (95% CI; 0.71 < RR <
      1.00). Gender and age had no bearing on primary compliance. CONCLUSIONS: Primary
      noncompliance is high in patients with asthma and is another factor contributing
      to morbidity. GPs should spend more time counselling patients on the need for
      treatment and not only its correct use. Patients with mild to moderate asthma and
      those in lower socioeconomic groups may need more intensive counselling.

PMID- 9009029
TI  - Cervical cytopathology reporting systems. Helping or hindering patient
      management?
AB  - OBJECTIVE: When a Pap smear is reported, the general practitioner needs to know
      whether it was technically satisfactory and, if abnormal, what kind of
      abnormality was found, in order to arrange appropriate management. A random
      survey of non hospital based cytology reporting laboratories in NSW was
      undertaken to determine the efficiency of this process. METHOD: This study
      examines the types of cytopathology reporting protocols used, the means provided
      by the laboratory to assist general practitioners in assessing the quality of
      their Pap smears and what, if any, management advice was given to general
      practitioners. RESULTS: Not only do different laboratories use different
      terminologies to report on Pap smears, but the majority use terms from at least
      two different reporting systems. Seven of the 10 laboratories provided feedback
      on the adequacy of the Pap smears while only 4 of the 10 laboratories provided
      management advice. CONCLUSIONS: If the 1993 National Health and Medical Research
      Council recommendations are followed, cytopathology reporting will be primarily
      Bethesda based with the pathology laboratories providing feedback on technical
      aspects of Pap smears taking as well as management advice.

PMID- 9009030
TI  - A survey of general practitioner's confidence in their management of elderly
      patients.
AB  - OBJECTIVE: To assess the confidence of GPs in assessing physical, psychological
      and social functioning in the elderly and managing complex multi-systems in
      cooperation with other services and resources in the community. METHOD: One
      hundred and ninety general practitioners in the Fairfield and Liverpool
      municipalities were mailed a self-administered anonymous questionnaire which
      assessed their confidence and barriers to caring for the elderly. RESULTS: One
      hundred and six general practitioners responded (response rate 55%) with complete
      questionnaires. Most felt confident in identifying the physical and psychological
      problems but few felt confident in identifying social problems. Common barriers
      were patient factors such as reluctance to acknowledge problems, and lack of
      time. They were equally confident in diagnosing and managing most specific
      conditions but less so for dementia, depression and functional limitation. While
      general practitioners rated liaison with geriatricians and primary care services
      highly, aged care assessment teams were perceived to be poor communicators.
      CONCLUSIONS: Although most general practitioners felt confident about their
      general management of their elderly patients, many felt less confident in
      identifying social problems. More education needs to be provided in 'shared care'
      of dementia, functional limitations, depression and incontinence.

PMID- 9009031
TI  - Assessing case records using monitor criteria developed from consensus
      guidelines.
AB  - OBJECTIVE: To develop criteria to enable the monitoring of general practitioner
      (GP) case records using consensus guidelines for conditions commonly managed in
      general practice and to measure how well the case records of a non random sample
      of GPs conformed to these criteria. METHOD: An iterative process was used to
      develop criteria from consensus guidelines for 19 conditions. Criteria were also
      developed to enable monitoring of the structure and content of the patient case
      record. A non random sample of GPs in Adelaide was approached to allow
      measurement of the content of their case records against these criteria. This
      measurement was undertaken by allied health professionals. An overall percentage
      score of conformity with the criteria was created for 10 acute, and six chronic
      conditions and for the patient case record review. These were rank ordered and
      Kendall's rank order correlation coefficients were used to compare the results in
      these three areas of practice. RESULTS: Criteria were successfully developed for
      each condition. Thirty-one GPs had their patient case records assessed. There was
      substantial variability between these practitioners in their conformity to the
      criteria. Kendall's rank order coefficients found statistically significant
      correlation between the results for acute and chronic conditions, and between
      acute conditions and the patient case record review section. CONCLUSION: It is
      feasible to develop criteria that enable measurement of the conformity of GP case
      records to these criteria. The overall level of conformity, together with the
      substantial variability found between practitioners suggest that there is a need
      for GPs to address this area of their practice.

PMID- 9009032
TI  - The skin cancer workload in Australian general practice.
AB  - OBJECTIVE: Skin cancer is common in Australia. It is managed in large portion
      within general practice, and early excision usually affords cure, therefore, it
      may form a much greater workload for general practitioners (GPs) than incidence
      figures would imply. The aim of this study was to describe the skin cancer
      workload in Australian general practice. METHOD: Analysis of data recorded by 495
      randomly selected GPs relating to 113,468 consultations (98,796 weighted for
      State size), which were collected as part of a national descriptive study.
      Medicare and census data were used to calculate rates at which GPs were consulted
      for different conditions. RESULTS: Skin tumours accounted for 2,083 (1.5%) of all
      145,799 problems managed in 98,796 encounters. Annual rates at which GPs were
      consulted were: 13/1,000 people for 'malignant' tumours of the skin; 23/1,000 for
      'naevus/mole; and 13/1,000 for 'other benign' lesions. The rates of diagnoses of
      'malignant skin neoplasms' increased with age to a maximum among women and men
      aged 65 years or more of > 80/1,000 and > 100/1,000, respectively. For
      'naevus/mole' the rates of maximum diagnoses were 40/1,000 for women and
      351/1,000 for men aged 15-24 years. There was no sex difference for the maximal
      rate (15/1,000) among the 45-64 age groups for 'other benign skin lesions'. The
      main form of management was procedural for malignant skin lesions (90% of
      consultations) and naevi/moles (50%). Referral to specialist services was most
      common during consultations for malignant disease (22% of consultations), in
      comparison to naevi/moles (15%) and other benign skin neoplasms (9%). Procedures
      (cryotherapy, diathermy and excision) and referrals were more common for
      malignant lesions and naevi/moles. CONCLUSIONS: There were important differences
      in age distribution for rates of management of benign and malignant skin tumours
      and naevi. Skin tumours usually were managed in conjunction with other problems.
      Most were managed procedurally. Only a minority were referred. Skin cancer
      represents a greater workload for Australian GPs than suggested by previous
      incidence reports.

PMID- 9009033
TI  - Evaluation of consulting skills of trainee general practitioners.
AB  - OBJECTIVE: This pilot survey was performed primarily to confirm the identity of
      areas of observed weakness in the consulting styles of young graduates, thus
      enabling educational models to be set up to correct any deficiencies. A secondary
      objective was to trial the design of a research instrument and detect and rectify
      any design flaws for subsequent and improved surveys. The consulting skills of 98
      GP registrars, enrolled in the various stages of the RACGP Training Program in
      Western Australia were surveyed. METHOD: A pilot survey was conducted using a
      recording form with a Likert rating format, designed to analyse certain defined
      areas of the consultation. This was conducted by skilled observers who explored
      five hypothesised areas of weakness. RESULTS: Seven areas of concern were
      identified in the consulting skills of GP Registrars, with consistency across the
      observers. Modest improvements of skills in some but not all of these parameters
      occurred in the later stages of the RACGP Training Program. CONCLUSION: One task
      of the pilot study was to assess the quality of the statements used with
      reference to the 14 aspects identified (items 9 to 22); the aim being to produce
      an improved instrument, with less chance of misinterpretation, in a further
      survey. Areas of concern were defined with some constancy across the raters and
      largely coincided with the hypothesised concerns. Suggestions for remedial
      educational input and for additional research into the same area are made.

PMID- 9009034
TI  - How do general practice registrars learn from their clinical experience? A
      critical incident study.
AB  - OBJECTIVE: This preliminary study of RACGP registrars in the period of subsequent
      general practice experience examines the types of clinical experiences from which
      registrars learn, what they learn from the experiences and the process of
      learning from such experiences. METHOD: A critical incident method was used on a
      semi structured interview process. Registrars were asked to recall clinical
      incidents where they had learnt something of importance. Data were sorted and
      categorised manually. RESULTS: Nine registrars were interviewed before new
      categories of data ceased to develop. Registrars learnt from the opportunity to
      follow up patients. An emotional response to the interaction was an important
      part of the learning process. Learning from such experiences is haphazard and
      unstructured. Registrars accessed human resources in response to their clinical
      difficulties rather than text or electronic based information sources.
      CONCLUSION: Registrars should be aware of their emotional responses to
      interactions with patients; these emotional responses often indicate important
      learning opportunities. Clinical interactions and resultant learning could be
      made less haphazard by structuring consultations with patients with specific
      problems. These learning opportunities should be augmented by the promotion of
      follow up of patients.

PMID- 9009035
TI  - Breast self examination: should general practice bother?
AB  - The value of breast self examination (BSE) for the early detection of breast
      cancer is causing debate in Australian general practice. A literature review was
      undertaken to examine this controversy. Evidence is conflicting on whether BSE
      causes earlier cancer detection and improved survival, although most studies
      support BSE. No mortality benefits are yet seen in prospective trials. Design
      biases in these studies are outlined, and conclusions are drawn about the place
      of BSE in the general practice setting.

PMID- 9009036
TI  - Academic general practice comes of age?
AB  - Academic general practice in Australia is 21 years old. In coming of age it has
      had to endure a very obstructed labour into Australian medical schools.
      Departments of General Practice have changed for the better and are being staffed
      by a new generation of academics, many of whom may lack historical perspective of
      the development of academic general practice. This article provides this
      historical perspective.

PMID- 9009037
TI  - Wants and needs in continuing medical education.

PMID- 9009038
TI  - Dissociative storage systems in human evaluative conditioning.
AB  - There is strong evidence in the literature that human evaluative conditioning can
      occur in the absence of conditioned stimulus-unconditioned stimulus (CS-UCS)
      (contingency) awareness, yet this evidence has been disputed on methodological
      grounds. The current study replicated evaluative conditioning with some
      procedural modifications, including the use of mental imagery as a way of
      associating a UCS with a CS picture, and tests of long-term retention of
      contingency memory and preference ratings. While the acquisition of evaluative
      responses was found to be significantly dependent upon contingency awareness
      (especially for pairings with unpleasant images), preference ratings for the CSs
      2 months later were still biased by their associated images but subjects could
      not recall the image for more than 90% of the pictures. These results demonstrate
      that performance of the evaluative response can occur independently of conscious
      memory for the contingencies involved, provide further support for a model which
      supposes the existence of dissociative storage structures in human classical
      conditioning.

PMID- 9009039
TI  - Ironic effects of trying to relax under stress.
AB  - Two studies found that intentional relaxation under conditions of mental load or
      stress produces ironic increases in skin conductance level (SCL). In Experiment
      1, participants instructed to relax under the high mental load of rehearsing a
      long number had higher SCL than those instructed to relax under low load, and
      tended to have higher SCL than those under high load not instructed to relax. In
      Experiment 2, participants were instructed to relax or were not so instructed
      while they answered questions described either as measures of IQ or as
      unimportant. Those in the more loading and stressful situation who were asked to
      relax had greater SCL during the questions than those not asked to relax.

PMID- 9009040
TI  - Parental history, aversive exposure and the development of snake and spider
      phobia in women.
AB  - Parental history and experiential factors in the development of snake and spider
      phobia were studied. Phobic women (DSM-IV, n = 158) reported on family history of
      animal phobia and whether direct (being frightened by the phobic object) or
      indirect (seeing someone else being frightened by and/or being warned of the
      phobic object) fear exposure predated phobia development. Fifty-nine mothers
      (37%) and 11 fathers (7%) had snake or spider phobia, which is higher than the
      upper 95% confidence interval in the populations (Fredrikson, Annas, Fischer &
      Wik, Behavior Research and Therapy, 34, 33-39). Lifetime Relative Risk, RR, of
      animal phobia in probands' mother and fathers as a function of at least one
      phobic grandparent was 3.3 and 13.7 respectively. Indirect fear exposures were
      more common in snake (45%) than spider (27%) phobics (RR = 1.4). Indirect fear
      exposures were more common among probands with a positive parental history, the
      RRs being 3.6 and 2.1 as a function of maternal and paternal family history.
      Direct exposures were unrelated to parental history. The familial resemblance and
      transmission of specific phobia could be experiential in origin mediated by
      indirect exposures or of hereditary origin mediated by genetic factors. It may
      represent genetically facilitated learning and exemplify imprinting in humans.

PMID- 9009041
TI  - Preconscious processing bias in specific phobia.
AB  - The occurrence of processing bias manifested by the modified Stroop task does not
      require that the subjects to be aware of the stimuli presented. Earlier studies
      have shown that even when stimuli are backwardly masked so conscious
      identification is prevented, patients suffering from Generalised Anxiety
      Disorders slow down colour-naming masks that are preceded by threatening words.
      In non-patient samples, processing bias on the modified Stroop task is related to
      the level of trait anxiety. We tested whether this preconscious processing bias
      is related to anxiety per se and whether it also occurs in specific phobias.
      Indeed, in a group of 37 spider phobics, the intensity of phobic complaints was
      significantly associated with interference measures on both the masked and the
      unmasked modified Stroop task. Preconscious processing bias was not associated
      with treatment gain. Interference on the masked and unmasked Stroop task was
      reduced after treatment. Though the lack of a no treatment control group preludes
      definite conclusions, our findings suggest that preconscious biases are
      influenced by behaviour therapy. Results are critically discussed.

PMID- 9009042
TI  - Covariation bias for blood-injury stimuli and aversive outcomes.
AB  - Three illusory correlation experiments were conducted to determine whether a fear
      relevant covariation bias (Tomarken, Mineka & Cook, 1989, Journal of Abnormal
      Psychology, 98, 381-394) could be demonstrated using different types of fear
      relevant stimuli from the blood-injury phobia category. In each experiment, women
      high and low on blood-injury fear were presented with fear-relevant slides
      depicting blood or injury, as well as slides from two neutral categories. A shock
      (aversive outcome), or a tone or no outcome (neutral outcomes) followed each by
      the 72 slides. Although the relationship between slide types and outcomes was
      random, subjects in all three experiments overestimated the co-occurrence of
      shock and blood-injury slides relative to all other slide-outcome combinations.
      However, there was no significant effect of blood-injury fear on this bias,
      indicating that, regardless of their blood-injury fear level, humans show an
      associative bias to selectively associate blood-injury stimuli with aversive
      outcomes.

PMID- 9009043
TI  - An information processing model of anxiety: automatic and strategic processes.
AB  - A three-stage schema-based information processing model of anxiety is described
      that involves: (a) the initial registration of a threat stimulus; (b) the
      activation of a primal threat mode; and (c) the secondary activation of more
      elaborative and reflective modes of thinking. The defining elements of automatic
      and strategic processing are discussed with the cognitive bias in anxiety
      reconceptualized in terms of a mixture of automatic and strategic processing
      characteristics depending on which stage of the information processing model is
      under consideration. The goal in the treatment of anxiety is to deactivate the
      more automatic primal threat mode and to strengthen more constructive reflective
      modes of thinking. Arguments are presented for the inclusion of verbal mediation
      as a necessary but not sufficient component in the cognitive and behavioral
      treatment of anxiety.

PMID- 9009044
TI  - Effects of suppressing the urge to drink on the accessibility of alcohol outcome
      expectancies.
AB  - Previous work has shown that attempts to deliberately suppress a given thought is
      associated with heightened accessibility of thought-related information both
      during and following suppression (Wegner, 1994, Psychological Review, 101, 34
      52). This study examined whether attempts to suppress the urge for alcohol would
      similarly be associated with heightened accessibility of alcohol-related
      information. Heavy social drinkers were exposed to the sight and smell of their
      usual alcoholic beverage either under the instructions to suppress their urge to
      drink alcohol or without such instruction. Following this task, participants were
      asked to make timed judgements about the applicability of a series of alcohol
      outcome expectancies. Results supported the view that suppression increases the
      accessibility of information in memory. Those in the Suppression condition were
      faster to endorse alcohol outcome expectancies following the exposure to alcohol
      cues than those in the Control condition. Findings are discussed in terms of
      cognitive strategies for regulating alcohol use and patterns of restrained
      drinking.

PMID- 9009045
TI  - Body dysmorphic disorder: a preliminary evaluation of treatment and maintenance
      using exposure with response prevention.
AB  - In recent investigations, body dysmorphic disorder (BDD) has been shown to share
      common etiological and symptom presentation to obsessive-compulsive disorder
      (OCD). When treating BDD, there have been some investigations suggesting that
      exposure with response prevention is effective in alleviating symptoms. Ten
      patients diagnosed with BDD participated in a study examining the effects of
      treatment and maintenance using exposure with response prevention. They received
      a standard behavior therapy protocol which consisted of exposure in vivo and in
      imagery, with response prevention. Symptom severity, depression, anxiety, and
      avoidance were assessed weekly during treatment. Following treatment, a 6-month
      maintenance program was instituted for five patients, with the other five serving
      as controls. Patients in the maintenance program were assessed bi-weekly with all
      measures and a 6-month follow-up was conducted. Patients improved for measures of
      avoidance, BDD symptoms, depression and anxiety when using exposure with response
      prevention. Although all patients remained symptom free at follow-up, those in
      the maintenance program continued to improve. Based on these results, BDD appears
      to be amenable to exposure with response prevention treatment. Additional
      treatment gains can be obtained when structured maintenance programs are
      implemented.

PMID- 9009046
TI  - Cognitions of restrained and unrestrained eaters under fasting and nonfasting
      conditions.
AB  - It has recently been suggested that the cognitions of unrestrained eaters and
      those of individuals with eating disorders are at opposing ends of a continuum,
      with restrained eaters occupying an intermediate position. The present study
      explored the everyday cognitions of 10 restrained and 10 unrestrained eaters
      under fasting and nonfasting conditions using a random thought-sampling
      technique. Analysis of the thought transcripts yielded a number of categories
      related to food, self, and others. The results revealed no differences between
      restrained and unrestrained eaters in terms of their relative percentages of
      thoughts about food and self. Differences were evident, however, in the nature of
      their cognitions. The results from this study suggest that the continuum
      hypothesis may hold only when it is the nature of cognitions, not their
      frequency, that is considered.

PMID- 9009047
TI  - The etiology of childhood dog phobia.
AB  - This study evaluated Rachman's theory of fear acquisition in a sample of 30
      children with dog phobia. The children were on the waiting list of a university
      based clinic. Parents were asked to indicate the most influential factor in the
      onset of their child's dog phobia. Nearly all parents were able to attribute
      their child's phobia to one of the fear pathways: direct conditioning, modelling
      or transmission of information.

PMID- 9009048
TI  - Psychometric properties of the Depression Anxiety Stress Scales (DASS) in
      clinical samples.
AB  - The psychometric properties of the Depression Anxiety Stress Scales (DASS) were
      evaluated in two studies using large clinical samples (N = 437 and N = 241). In
      Study 1, the three scales comprising the DASS were shown to have excellent
      internal consistency and temporal stability. An exploratory factor analysis
      (principal components extraction with varimax rotation) yielded a solution that
      was highly consistent with the factor structure previously found in nonclinical
      samples. Between-groups comparisons indicated that the DASS distinguished various
      anxiety and mood disorder groups in the predicted direction. In Study 2, the
      conceptual and empirical latent structure of the DASS was upheld by findings from
      confirmatory factor analysis. Correlations between the DASS and other
      questionnaire and clinical rating measures of anxiety, depression, and negative
      affect demonstrated the convergent and discriminant validity of the scales. In
      addition to supporting the psychometric properties of the DASS in clinical
      anxiety and mood disorders samples, the results are discussed in the context of
      current conceptualizations of the distinctive and overlapping features of anxiety
      and depression.

PMID- 9009049
TI  - An "in vitro" approach to water pollution monitoring.
AB  - Pollutants of River Lambro, a tributary River Po, were monitored by their
      potential to induce 1A1 isoform of cytochrome P450 in the FaO hepatoma cell line.
      Extracts of water samples taken during different months over about one year were
      fractionated by reverse phase HPLC technique. Six fractions of decreasing
      polarity were collected, concentrated, freeze-dried and suspended in DMSO for the
      treatment of the cells. Aliquots of such suspensions were dissolved in the growth
      medium and left for 48 h in contact with FaO cells, that were maintained in 24
      well plates. Cellular monolayers were also exposed to a mixture of the six
      fractions, to evaluate the effects of all the pollutants mixed together in the
      original water sample. The CYP1A1-dependent ethoxyresorufin-O-deethylase (EROD)
      activity was fluorimetrically detected as a measure of inducing potential, and
      total protein content was evaluated as cytotoxicity end-point. The results showed
      significant increases of EROD activity over the controls in nearly all the
      fractions with marked reduction of viability only in two of the mixed samples.
      The effects of the mixtures were not simply additive, thus suggesting both
      synergistic and antagonistic interactions. The potential utility of this simple
      and fast bioassay in environmental risk/hazard assessment is clearly apparent.

PMID- 9009050
TI  - Thyroid hormone affects rat uterine expression of IGF-I and IGFBP-4.
AB  - The rat uterus has been shown to be a site of production of insulin-like growth
      factor-I (IGF-I) and multiple IGF-binding proteins (IGFBP-2, -3, -4, -5, -6)
      which are involved in estrogen-induced uterine proliferation. The presence of T3
      receptors in rat uterus suggests a role of thyroid hormone in the regulation of
      uterus responses to estradiol. In this study IGF-I and IGFBP-4 mRNAs in uterus,
      oviduct and cervix from euthyroid, hypothyroid and T3-treated rats were
      quantified by Northern blot analysis. Our results demonstrate: i) a marked
      decrease in IGF-I and IGFBP-4 mRNA levels in the uterus but an increase in the
      oviduct of hypothyroid rats; ii) a marked increase in IGF-I and IGFBP-4 mRNA
      levels in the uterus but a net decrease in the cervix of T3-treated rats. The
      uterine changes in IGF-I and IGFBP-4 mRNA levels associated with hypothyroid
      status were in agreement with those observed in liver.

PMID- 9009051
TI  - Relationship between DNA synthesis and growth factor expression in primary
      cultures of adult rat hepatocytes.
AB  - In this study we employed primary culture of adult rat hepatocytes to verify the
      effects of two different extracellular matrices (collagen, matrigel) on EGF
      stimulated DNA synthesis and c-myc expression. Our results confirm that in adult
      rat hepatocytes EGF induces DNA synthesis, preceded by a transient increase of c
      myc expression, when cells are cultured at low density on collagen. DNA synthesis
      appears to be in reciprocal relationship with hepatic expression of IGF-I, IGFBP
      1, IGFBP-2 and IGFBP-4, suggesting that IGF-I/IGFBPs system is not involved in
      liver growth.

PMID- 9009052
TI  - Recurring intracranial meningiomas. Morphometrical evaluation of nuclear
      pleomorphism by S.A.M. (shape analytical morphometry) system.
AB  - Meningiomas are the most common neoplasms of the central nervous system and their
      biological behavior is not always predictable from the histologic appearance of
      the tumors. The nuclear pleomorphism seems to be one of the most important
      morphological features in the prediction of recurrence. By using analytical
      morphometric methods it is possible to quantify nuclear atypias and to obtain
      parameters describing nuclear contour irregularities and distortions of the
      figure. Moreover the amount of information obtained from analytical procedure
      allowed to discriminate, by multivariate discriminant analysis recurrent or no
      recurrent meningiomas (5% of error).

PMID- 9009053
TI  - Involvement of nitric oxide in hyporeactivity of rat mesenteric vascular bed
      during endotoxic shock: effect of dexamethasone and endothelin-I.
AB  - The present study was carried out on mesenteric vascular bed from LPS-injected
      rats in order to investigate the cause of hyporesponsiveness in resistance blood
      vessels, during septic shock syndrome. The involvement of L-Arg/NO pathway was
      evaluated by administration of L-Arg, which produced a decrease in perfusion
      pressure in LPS-treated rats, whereas it was ineffective in control rats.
      Furthermore, DEX-pretreatment in endotoxaemic rats significantly reduced the
      vasorelaxation by L-Arg, whereas it was ineffective to reverse vascular
      hyporeactivity occurring in septic shock. In order to evaluate whether
      hyporesponsiveness could be due to defects in contraction mechanisms, we tested
      the effect of ET-I. This peptide was able to markedly enhance the contractile
      response to NA in LPS-treated rats. Our findings suggest that vascular
      hyporesponsiveness during septic shock may depend on both activation of the L
      Arg/NO pathway and alterations in post-receptor mechanisms involving calcium
      handling.

PMID- 9009054
TI  - Influence of thyroid hormone on Sertoli cell protein metabolism in the
      prepubertal pig.
AB  - In order to better understand the role of thyroid hormones in testis development,
      the influence of tri-iodothyronine on protein metabolism of immature pig Sertoli
      cells has been investigated. Sertoli cells were isolated enzymatically from 2- to
      3-week-old piglet testes and cultured in the presence or absence of tri
      iodothyronine. Protein labelling was evaluated in Sertoli cell monolayers
      incubated in medium containing a tracer dose of [3H]leucine. The results
      demonstrate that thyroid hormone can directly stimulate the process of protein
      synthesis in immature porcine Sertoli cells, without significantly affecting the
      protein degradation rate; moreover thyroid hormone exposure results in a
      significant decrease of intracellular ATP level. The evidence that tri
      iodothyronine can increase Sertoli cell protein synthesis, supplies additional
      evidence about the fundamental role of thyroid hormone in the regulation of
      growth and differentiation of the mammalian testis through a direct action on the
      Sertoli cells.

PMID- 9009055
TI  - Cytogenetic effect of thiabendazole and diphenylammine on cultured human
      lymphocytes: sister chromatid exchanges and cell cycle delay.
AB  - The two fungicides analysed in this paper, Thiabendazole (TBZ) and Diphenylammine
      (DPA), are among the pesticides found in higher concentration in fruits and
      vegetables sold in Tuscany. These compounds were tested in "in vitro" lymphocyte
      cultures at different concentrations and using 3 protocols; protocol 1: the
      cultures were treated with the fungicides for 48 h; protocols 2 and 3: the
      cultures were treated with fungicides for 4 h in the presence or absence of the
      metabolic activator S9 mix. Both fungicides produced a slight increase in the SCE
      frequency in the 48 h treatment, at the higher non-toxic concentrations tested,
      but not when exposed for only 4 h, with or without S9 mix. As far as concerns the
      Proliferation Rate Index (i.e. the number of first, second and third mitoses),
      Thiabendazole also produced a significant decrease in the replication rate of the
      treated cultures, while Diphenylammine did not produce any effect.

PMID- 9009056
TI  - Looking for statistical stability: a new method of evaluating reliability of
      statistical tests.
AB  - A new method of looking for statistical reliability, stability calculation, is
      described and is applied to statistical tests. Alike the power of statistical
      tests, stability calculation enables us to assess reliability of the latter. It
      belongs to the category of subsampling techniques that require using subsamples
      taken from the original sample. It provides descriptive and non-inferential
      results indicating the stability percentage: the percentage of sample elements to
      be removed, in order to change results obtained with the original sample. The
      higher is the stability percentage the more reliable is the statistical test.
      Stability percentage and power are correlated. Stability calculation provides
      informations about the elements in the sample, the most powerful points.

PMID- 9009057
TI  - Study of C-polymorphisms of chromosomes 1, 9 and 16 in lymphocytes of patients
      with laryngeal carcinoma.
AB  - A case-control study of the C-bands of #1, 9 and 16 was performed on PHA
      stimulated lymphocytes in 29 individuals, 16 of whom with laryngeal carcinoma. C
      bands were revealed using Sumner's CBG staining technique. The assay for
      chromosomic markers was performed using traditional measuring methods and an
      image analysis system. The calculation of the heterochromatic index (HI) using
      Neeley's method was chosen to evaluate size heteromorphisms and was used for each
      homologue of chromosome pairs examined. No significant difference was found
      between patients and controls with regard to size polymorphisms. The comparison
      between patients and controls was significant when size polymorphisms at the
      level of #9 were taken into account. In fact, 9 out of 16 patients (56%) versus 2
      out of 13 controls (15%) presented a partial pericentric inversion on one of the
      two homologues of chromosome pair 9 (chi 2 = 5.325; 0.05 > p > 0.01). The two
      measuring techniques produced broadly similar results. However, in our opinion,
      the classic method is preferable owing to its simplicity of use. In conclusion,
      we affirm that pericentric inversion of #9 may be regarded as a predisposing
      factor for the onset of laryngeal carcinoma whose manifestation is triggered by
      tobacco and alcohol consumption.

PMID- 9009058
TI  - Catalase against met-Hb excess during oximetries of dilute Hb-A samples.
AB  - Functional parameters of diluted Hb-A have been determined before and after
      addition of catalase and disodium-EDTA to the samples. There are no important
      differences between the results drawn from catalase added samples and catalase
      free ones, except for the fact the met-Hb level at pH 7.8 is significantly lower
      in the samples containing catalase. On the contrary, catalase is almost
      ineffective against met-Hb at pH 6.8, whereas its activity at pH 7.3 is rather
      modest. Another limitation is that catalase remains active against met-Hb for not
      more than 15-20 minutes after addition to the sample, which is just the time
      necessary for one complete (manual) oximetry.

PMID- 9009059
TI  - Fibrillogenesis in tendon healing: an experimental study.
AB  - The aim of this study was the histochemical, immunohistochemical and
      ultrastructural analysis of reparative fibrillogenesis in experimental lesions of
      Achilles' tendon. Subtotal tenotomy of Achilles' tendon was performed in twenty
      Wistar rats. The scar tissue was analysed 2, 4, 7, 14, 21, 30, 45 and 60 days
      post-operatively. Histochemical, (resorcin-fuchsin, aldehyde-fuchsin, iron
      haematoxylin and Fullmer and Lillie's methods) immunohistochemical (antibody
      against collagen I, II and elastin) and ultrastructural analyses were performed.
      Three phases in the healing process were distinguished: 1) inflammatory, 2)
      proliferative, and 3) remodelling phase. The inflammatory phase was characterised
      by haematoma, fibrin deposition, inflammatory cells, fibroblasts, beginning of
      collagen fibrillogenesis (200-400 A o fibrils) and oxytalan fibrils. The
      proliferative phase was characterised by angiogenesis and fibroblast
      proliferation. Collagen fibres displayed a random arrangement and had a diameter
      of 400-600 A. Immature elastic fibres reached maximum tissutal concentration. In
      the remodelling phase, hypocellularity, normal vascularisation, tendon crimps,
      collagen fibres (800-1,000 A o), elastic fibres with increased elastin deposition
      and reduction in oxytalan fibres were observed. In the course of the healing
      process collagen and elastic fibre fibrillogenesis exhibited consistent
      quantitative and qualitative variations (i.e. differences in the type and
      diameter of fibrils). The present study suggests that, together with other matrix
      macromolecules, also elastic fibres (oxytalan, elaunin and mature) are
      synthesised in significantly higher amounts during reparative fibrillogenesis and
      play a role in cell-matrix interaction.

PMID- 9009060
TI  - Fasting/refeeding enhances the development of mammary tumors induced by
      methylnitrosourea in the rat.
AB  - The effect of fasting/refeeding on MNU-induced mammary carcinogenesis was
      investigated. Female Sprague-Dawley rats were given i.p. a single dose of MNU (50
      mg/Kg body weight) and beginning 1 week after MNU administration were exposed to
      3 cycles of 3 days fasting followed by refeeding (10 days). Rats were palpated
      twice a week and killed when tumor diameter was about 2 cm. Tumors palpated were
      registered by location. The exposure to fasting/refeeding after initiation
      increased the total number of mammary tumors about 2-fold compared to full-fed
      control group. In addition, fasted rats developed about 3-fold mammary tumors in
      the cervical-thoracic gland chains versus the abdominal-inguinal gland chains,
      while no difference in tumor distribution was observed in controls. The present
      study reports that fasting/refeeding enhances the development of MNU-induced
      mammary tumors.

PMID- 9009061
TI  - The delay in rat liver regeneration by choline is associated to alteration in c
      myc expression.
AB  - Previous data of our laboratory showed that female rats regenerated earlier than
      males and choline shifted the female growth pattern toward that of males. We
      investigated if the effect of choline on the liver compensatory growth was
      associated to a modulation of the expression and methylation pattern of an early
      cell cycle dependent proto-oncogene, c-myc. The peak of DNA synthesis was 22 h
      after 2/3 partial hepatectomy in female regenerating liver, while it was delayed
      to 30 h when female rats received choline for 3 weeks before liver surgery.
      Partial hepatectomy induced the expression of c-myc that was already maximal at 1
      h. Choline reduced the c-myc expression and it shifted the maximum increase at 2
      h. The methylation pattern of c-myc was studied with the Hpa II restriction
      enzyme. The delay in c-myc expression was not due to hypermethylation of the
      gene.

PMID- 9009062
TI  - Perivascular localization of TRPM1- and TRPM2-positive cells in the rat brain.

PMID- 9009063
TI  - Constituents of seminal plasma and blood serum of the ram.

PMID- 9009064
TI  - Spore photoproduct lyase operon (splAB) regulation during Bacillus subtilis
      sporulation: modulation of splB-lacZ fusion expression by P1 promoter mutations
      and by an in-frame deletion of splA.
AB  - EsigmaG-dependent transcription of the splAB operon in the forespore at stage III
      of Bacillus subtilis sporulation initiates from two promoters, P1 preceding splA
      (major) and P3 preceding splB (minor). To explore the possible role of splA in
      controlling splB-encoded spore photoproduct lyase expression, we measured beta
      galactosidase from splB-lacZ fusions integrated at the SPbeta prophage locus
      which contained point mutations or deletions which either inactivated or
      physically removed P1 and/or splA. Paradoxically, inactivation of P1 by point
      mutation or its removal by deletion from upstream resulted in elevated beta
      galactosidase expression of the resulting splB-lacZ fusion, as did an in-frame
      deletion of splA which left P1 and P3 intact;however, expression of all fusions
      remained sporulation specific and EsigmaG dependent.

PMID- 9009065
TI  - Transformation of pBR322-Derived Plasmids in PhytopathogenicPseudomonas avenae
      and Enhanced Transformation in ItsProline-Auxotrophic Mutant
AB  - Efficient transformation of pBR322 and its derivedplasmids, which have been
      widely used as cloning vectors in Escherichiacoli, was observed in Pseudomonas
      avenae (K1), the pathogen ofleaf blight disease in cereals. Moreover, there was a
      10- to 50-foldtransformation efficiency (1.3-3.0 x 10(6)/&mgr;g DNA) in
      theproline-auxotrophic mutant (Pr47), whose virulence to rice seedlingsdecreased.
      Similar enhancement of the frequency of transfer by mobilizationof RSF1010, a
      broad host range plasmid, was observed in the recipient Pr47strain in mating with
      donor Pseudomonas syringae. The plasmidsharbored in these strains were maintained
      very stably after subcultures.Thus, a highly efficient transformation system with
      pBR322-derived plasmidsused as a vector and Pseudomonas as a host bacterium was
      developed.

PMID- 9009066
TI  - Bacillus sphaericus penicillin V acylase: purification, substrate specificity,
      and active-site characterization.
AB  - Penicillin V acylase from Bacillus sphaericus was purified to homogeneity with an
      overall yield of 15%. The enzyme exhibited comparatively high specificity for
      penicillin V, penicillin G, and other related compounds being hydrolyzed at less
      than 10% of the rate of penicillin V. Moreover, the high rate of hydrolysis was
      observed when the side chain of the substrate molecule was unsubstituted. Lysine
      modifying reagents inactivated the enzyme rapidly. Kinetics and titration studies
      indicated the involvement of lysine in the catalytic activity of the enzyme.

PMID- 9009067
TI  - Immunization with temperature-sensitive mutants of Actinobacillus
      pleuropneumoniae induces protective hemolysin-neutralizing antibodies in mice.
AB  - The immunogenicity and protective potential of three temperature-sensitive
      mutants of Actinobacillus pleuropneumoniae were evaluated in mice with respect to
      antibodies against the capsular polysaccharide, lipopolysaccharide, outer
      membrane proteins, and hemolysin protein. Antibodies to the capsular
      polysaccharide and lipopolysaccharide could not be correlated with protection in
      the mice; there were no significant differences among the anti-capsular and anti
      lipopolysaccharide antibody titers regardless of the severity of infection. Sera
      from mice immunized with the mutants and challenged with the wild type contained
      antibodies that reacted in immunoblots to four major outer membrane proteins(66,
      39, 29, and 16 kDa) regardless of the severity of infection after challenge. Both
      the tight and coaster mutants synthesized and secreted the 105-kDa hemolysin
      protein exotoxin in vitro and in vivo; hemolysin protein neutralization titers
      and the blotting intensity of the sera, however, varied inversely with the
      severity of infection. Sera from mice surviving challenge with little to no lung
      involvement stained the hemolysin band more intensely and had significantly
      higher neutralization titers (P < 0.05) than sera from mice that either died or
      survived with severe pulmonary hemorrhage. These results confirm the importance
      of the hemolysin in pathogenesis and the need for including it in any vaccine
      preparation.

PMID- 9009068
TI  - Association of LHIalpha(B870) polypeptide with phospholipids during insertion in
      the photosynthetic membrane of an LHII- mutant of Rhodobacter capsulatus.
AB  - Membranes from in vivo labeled cells of Rhodobacter capsulatus U43[pTX35] grown
      photosynthetically carried 60% of the [32P]-Pi in the "heavy" fraction (HM) after
      sucrose gradient sedimentation. Metal-chelating chromatography of either"heavy"
      or "light" (LM) membrane fractions rendered similar Bchl-protein complex profiles
      after octyl-glucoside treatment,including most of the radioactivity in the same
      corresponding elution fraction (F II). Similar labeling distribution of pigment
      protein complexes was obtained for membranes of dark-grown cells induced by
      lowering oxygen tension. Fractions derived from HM showed highly labeled
      LHIalpha, whereas the same complex from LM was essentially [32P]-Pi-free, as
      revealed by SDS-PAGE followed by autoradiography. Phospholipid analysis showed a
      similar pattern for membranes isolated from cells photosynthetically or
      semiaerobically grown, being the most abundant:
      phosphatidylglycerol,phosphatidylethanolamine, cardiolipin, and
      phosphatidylcholine. Part of the phospholipids from HM comigrated with LHIalpha
      during SDS-PAGE and dissociated from the complexes only after solvent extraction
      and hydrophobic chromatography. However, a small amount remained always attached
      to LHIalpha,indicating an unusual strong interaction. These results suggest the
      existence of two operationally defined membrane regions carrying LHIalpha
      complexes differing in phosphorylation status and protein-phospholipid
      interaction.

PMID- 9009069
TI  - NAD-independent lactate and butyryl-CoA dehydrogenases of Clostridium
      acetobutylicum P262.
AB  - Clostridium acetobutylicum P262 cells that were growing on lactate and acetate
      had an NAD-independent lactate dehydrogenase(iLDH) activity of 200 nmol mg
      protein-1 min-1. Ammonium sulfate precipitation and DEAE cellulose caused a 35
      fold purification. Gel filtration indicated that the iLDH had a molecular weight
      of approximately 55 kDa, but two bands were always observed. Phenyl sepharose
      could not separate the two proteins, and hydroxyapatite caused a complete loss of
      activity. The semi-purified iLDH had a Vmax of 13,000 nmol mg protein-1 min-1 and
      a Km value of 3.5 mM for D-lactate. The Vmax and Km values for L-lactate were 300
      nmol mg protein-1 min-1 and 0.7 mM. The iLDH had a pH optimum of 7.5, was not
      activated by fructose-1,6-bisphosphate (FDP), and could be coupled to either 3
      (4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or
      dichlorophenol-indophenol (DCPIP), but not methyl viologen (MV) or benzyl
      viologen (BV). The iLDH did not have strong absorbance between 500 and 300 nm,
      and trichloroacetic acid or acid ammonium sulfate extracts had virtually no
      fluorescence at 450 nm. The crude extracts also had MTT-linked butyryl-CoA
      dehydrogenase activity (60 nmol mg protein-1 min-1). The NAD-independent butyryl
      CoA dehydrogenase eluted from DEAE-cellulose as two fractions. The yellow
      fraction was extremely unstable, but the green fraction could be stored for short
      periods of time at 5 degrees C. The green-colored butyryl-CoA dehydrogenase had
      strong absorption at 450 nm, and gel filtration indicated that it had a molecular
      weight of 90 kDa. The NAD-independent butyryl-CoA dehydrogenase could be coupled
      to MTT, DCPIP, or MV, but not BV. Because the NAD-independent lactate and butyryl
      CoA dehydrogenase could both be linked to low potential carriers, these two
      enzymes may function as oxidation-reduction system in vivo.

PMID- 9009070
TI  - Choline and glycine betaine uptake in various strains of Rhizobia isolated from
      nodules of Vicia faba var. major and Cicer arietinum l.: modulation by salt,
      choline, and glycine betaine.
AB  - Two strains of Rhizobia isolated from nodules of Vicia faba var. major and one
      strain isolated from nodules of Cicer arietinum L. were characterized for salt
      resistance. The presence of 1 mM glycine betaine or choline in a minimal medium
      with added NaCl had a beneficial role on the growth of the three strains. Both
      molecules were found to be taken up by cells obtained at low osmolarity, and
      whereas glycine betaine uptake activity was stimulated significantly in cells
      grown in the presence of 0.15 M NaCl, choline uptake activity was strongly
      inhibited by salt in all tested strains. However, in cells grown with exogenous
      choline,the uptake inhibition exerted by salt was relieved, mainly in the strain
      isolated from nodules of C. arietinum L. On the basis of kinetics determinations,
      in control cells as well as in salt-stressed cells, only high-affinity activities
      were observed for glycine betaine and choline(apparent Kms between 3 and 18
      micro;M). Periplasmic proteins that bound glycine betaine or choline were
      identified. In nondenaturing conditions, these proteins extracted from the
      various strains showed different electrophoretic mobility with always a less
      negative entire charge than the analogous proteins from Rhizobium meliloti.

PMID- 9009071
TI  - Purification and partial amino acid sequence of brevicin 27, a bacteriocin
      produced by Lactobacillus brevis SB27.
AB  - Brevicin 27, a bacteriocin produced by Lacto bacillus brevis SB27, is inhibitory
      mainly against closely related Lactobacillus brevis and Lactobacillus buchneri
      strains. It was purified from the culture supernatant by a four-step purification
      procedure including ammonium sulfate precipitation, cation exchange, hydrophobic
      interaction, and reverse-phase, high performance liquid chromatographies. The
      purified bacteriocin was subjected to mass spectrometry, amino acid composition
      analysis, and sequencing by Edman degradation. It was shown to be an about 5200
      Da basic protein containing a high proportion of lysine and of hydrophobic amino
      acids. The partial N-terminal amino acid sequence (25 residues) was unique when
      compared with the Protein Data Bank (PDB), Swiss Prot, and Protein Information
      Resource(PIR) data banks and to the translated Gen Bank.

PMID- 9009072
TI  - Lactobacillus helveticus: strain typing and genome size estimation by pulsed
      field gel electrophoresis.
AB  - Genomic DNAs of 22 strains of Lactobacillus helveticus of various geographical
      origins were analyzed by pulsed-field gel electrophoresis. Two endonucleases,
      SmaI and SgrAI, of the 19 tested produced DNA fragments useful for strain
      comparison. With the endonuclease SmaI, a characteristic restriction pattern was
      identified for 18 of the 22 strains. The percentage of similarity (Dice
      coefficient) between the profiles varied between 26% and 100%, and clustering was
      accomplished by using the unweighted pair group method with arithmetic averages
      (UPGMA). For the strains showing identical profiles,the high genomic similarity
      was confirmed when the endonuclease SgrAI was used instead of SmaI. From
      summation of SmaI and SgrAI fragments from three L. helveticus strains(CNRZ 241,
      CNRZ 303, and CIP 57.15), the genomic length was estimated at ca.1. 85-2.0 Mb.

PMID- 9009073
TI  - Purification of glucoamylase from Lactobacillus amylovorus ATCC 33621.
AB  - An intracellular glucoamylase (E.C. 3.2.1.3) was purified to homogeneity from
      Lactobacillus amylovorus on a Fast Protein liquid chromatography System (FPLC)
      with a Mono Q ion-exchanger and two Superose 12 gel filtration columns arranged
      in series. The enzyme activity was quantified with a specific, chromogenic
      substrate, p-nitrophenyl-beta-maltoside. Preparative gel electrophoresis was then
      used to further purify active enzyme fractions. Native polyacrylamide gel
      electrophoresis (Native-PAGE) and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) of the purified enzyme showed a single protein band of
      molecular weight 47 kDa. Glucoamylase activity of the purified protein was
      confirmed by its ability to degrade starch on a 0.025% starch-polyacrylamide gel
      stained with I2/KI. Glucoamylase exhibited optimum catalytic activity at pH 6.0
      and 45 degrees C, and the enzyme had an isoelectric point near 4.39. The
      glucoamylase contained high levels of hydrophilic amino acids, comparable to
      fungal glucoamylases.

PMID- 9009075
TI  - A high-density molecular genetic map around the weaver locus

PMID- 9009074
TI  - Use of trinitrobenzene as a nitrogen source by Pseudomonas vesicularis isolated
      from soil.
AB  - An aerobic Gram-negative bacterium identified as Pseudomonas vesicularis was
      isolated from soil contaminated with 2,4, 6-trinitrotoluene (TNT) and 1,3,5
      trinitrobenzene (TNB). This bacterium used TNB as the sole source of nitrogen.
      The TNB was metabolized within 80 h of incubation. The major metabolites produced
      were dinitroaniline,dinitrobenzene (DNB), nitroaniline, nitrobenzene (NB), and
      ammonia. The concentrations of DNB and NB produced in the culture medium were
      nearly stoichiometric. The ammonia concentration in the culture medium increased
      during the course of incubation. The end product of TNB metabolism was NB,which
      did not undergo further degradation even after long incubation time. This
      bacterium could be used in a syntrophic culture system with other NB-degrading
      bacteria to remove TNB completely from soil and water at contaminated sites.

PMID- 9009076
TI  - Pharmacological approach for optimization of the dose schedule of 5-Aza-2'
      deoxycytidine (Decitabine) for the therapy of leukemia.
AB  - 5-Aza-2'-deoxycytidine (5-Aza-CdR; Decitabine) is an active antineoplastic agent
      in patients with leukemia. Since 5-Aza-CdR is an S phase specific agent and has a
      short plasma half-life, its antileukemic activity is dose schedule-dependent.
      Leukemia patients who are candidates for 5-Aza-CdR therapy following relapse
      after therapy with cytosine arabinoside are at greater risk for the problem of
      drug resistance since these cytosine nucleoside analogues are metabolized by the
      same enzymes. Due to its unique mechanism of action of demethylating DNA, 5-Aza
      CdR has the potential to activate tumor (growth) suppressor and differentiation
      genes that have been accidentally silenced by DNA methylation in leukemic cells.
      All these factors should be taken into account in the design of the optimal dose
      schedule of this analogue. The optimal dose schedule of 5-Aza-CdR should be based
      on the kinetic parameters of deoxycytidine kinase, its pharmacokinetics, its
      effects on DNA methylation and the cell cycle parameters of the leukemic cells
      and the normal hematopoietic stem cells. Since granulocytopenia is the major
      toxic effect produced by 5-Aza-CdR, the use of hematopoietic growth factors to
      shorten the duration of leukopenia should be investigated. Another approach which
      we are investigating is to use the methods of gene therapy to insert the cytidine
      deaminase gene into normal hematopoietic progenitor cells so as to make them drug
      resistant to 5-Aza-CdR. The use of other agents that can induce the
      differentiation of leukemic cells in combination with 5-Aza-CdR may have the
      potential to increase the clinical effectiveness of this analogue for the therapy
      of leukemia.

PMID- 9009077
TI  - SHIP, a new player in cytokine-induced signalling.
AB  - We recently purified and cloned the cDNAs for the murine and human forms of a
      novel 145 kDa inositol polyphosphate 5-phosphatase (5-ptase) that becomes
      tyrosine phosphorylated and associated with Shc following stimulation of
      hemopoietic cells with multiple cytokines. Unlike most 5-ptases which hydrolyze
      phosphatidylinositol-4,5-P2-bisphosphate (PI-4,5-P2) and/or inositol-1,4,5
      trisphosphate (I-1,4,5-P3), this enzyme selectively hydrolyzes the 5'-phosphate
      from inositol-1,3,4,5-tetraphosphate (I-1,3,4,5-P4) and phosphatidylinositol
      3,4,5-trisphosphate (PI-3,4,5-P3), two inositol polyphosphates recently
      implicated in growth factor-mediated signalling. This 5-ptase is also unique
      among 5-ptases in that it is the only one to date to possess an SH2 domain. In
      this review we discuss the cloning, the Shc binding and the potential role of
      this protein, which we call SHIP, for SH2-containing inositol 5-phosphatase, in
      cell proliferation, differentiation and apoptosis.

PMID- 9009078
TI  - High-dose cytosine arabinoside and etoposide: an effective regimen without
      anthracyclines for refractory childhood acute non-lymphocytic leukemia.
AB  - The purpose of this report is to describe the tolerability and activity of the
      combination of high-dose cytosine arabinoside (Ara-C) given at the maximum
      tolerated dose of 36 g/m2, together with high doses of etoposide in relapsed and
      refractory childhood acute leukemias. Eighteen children with relapsed or
      refractory acute leukemia were treated with Ara-C 3 g/m2 every 12 h on days 1-6,
      followed by etoposide 400 mg/m2 on days 7-9 (HDAC/VP-16). Eight children with
      refractory disease received HDAC/VP-16 as salvage induction therapy after failing
      conventional induction regimens; four of five refractory ANLL patients (80%) had
      a complete response (CR) after HDAC/VP-16 therapy. Ten patients received HDAC/VP
      16 as post-remission intensification therapy; five patients (four ANLL, one
      relapsed ALL) remain in second CR at 56, 26, 9, 5 and 2 months. Toxicities were
      primarily hematologic and dermatologic. Seven patients (39%) developed bacterial
      or fungal infections; four patients developed grade 3 or 4 acral erythema. No
      patient died of therapy-related toxicity. The combination of 36 g/m2 cytosine
      arabinoside and 1200 mg/m2 etoposide is an effective regimen for children with
      relapsed or refractory acute nonlymphocytic leukemia, with tolerable toxicities;
      the absence of anthracyclines makes this regimen suitable for patients who have
      previously received maximal doses of anthracyclines or who have evidence of
      cardiac dysfunction. Further evaluation of this regimen in acute nonlymphocytic
      leukemia is presently being investigated.

PMID- 9009079
TI  - Telomerase activity and cytogenetic changes in chronic myeloid leukemia with
      disease progression.
AB  - Progressive telomere shortening is thought to be important in the regulation of
      cellular senescence and that the upregulation or reactivation of telomerase
      activity may be a critical if not rate limiting step in the development of
      neoplastic cells. To obtain information about telomeres and telomerase activity
      in hematopoietic neoplasia at various disease stages, we evaluated 54 samples
      obtained from 41 patients with chronic myeloid leukemia (CML) using a combination
      of fluorescent-telomeric repeat amplification protocol and an internal telomerase
      assay standard. The terminal restriction fragment (TRF) lengths in the blast
      phase was reduced compared to that in the chronic phase (4.53 +/- 0.72 kb vs 6.13
      +/- 1.68 kb; P = 0.0005). All samples obtained from CML in the chronic phase (n =
      33) had detectable telomerase activity above background, regardless of age. In
      the blast phase (n = 21), a significant increase of telomerase activity was
      detected compared to that in the chronic phase (33.84 +/- 37.86% vs 6.08 +/-
      3.21; P = 0.016). Among patients in the blastic phase, 50% of patients had
      moderate to high telomerase activity (>10 relative value), and the remaining
      patients had telomerase activity higher than that in the normal peripheral blood
      cells. No significant differences in hematologic findings, duration of chronic
      phase or blast phase, and telomere length in the blastic phase were noted between
      these two groups separated by telomerase activity. CML patients with moderate to
      high telomerase activity had a high frequency of additional cytogenetic changes
      (P = 0.01).

PMID- 9009080
TI  - Clonal instability preceding lymphoid blastic transformation of chronic myeloid
      leukemia.
AB  - We have sought the presence of rearrangements of the immunoglobulin heavy chain
      gene locus in 13 patients with chronic myeloid leukemia (CML) in lymphoid blastic
      transformation (L-BT) using the polymerase chain reaction (PCR). The lymphoid
      nature of the transformation was confirmed by immunophenotyping and/or Southern
      blot hybridization with a J(H) probe. Clonal rearrangements were detected in 85%
      of cases and two or more rearrangements were visible in 64% of informative cases.
      The pattern of V(H) gene family utilization revealed an apparent reduction in
      V(H)4 family gene usage but otherwise reflected the known proportion of each gene
      family in the germline repertoire. In six cases the third complementary
      determining regions (CDR3) of the predominant blast crisis clone/s were sequenced
      revealing minimal evidence of somatic mutation. No clonal changes were detected
      in the chronic phase leukemia cells collected more than 6 months before the onset
      of L-BT in three of these patients. Of the other three patients studied in
      chronic phase from 1 to 6 months before L-BT, two showed clonal rearrangements
      which differed in size from those present at L-BT. In one patient a V(H)3 to
      V(H)5-D(H)-J(H) substitution had occurred at least 3 months prior to L-BT. In the
      other patient, however, the sequence of the rearrangement present 5 months prior
      to L-BT was unrelated to the rearrangements at the time of L-BT indicating a
      pattern of clonal succession. We conclude that: (1) IgH gene rearrangements are
      detectable in the majority of patients with L-BT using PCR and the lymphoid
      lineage of blastic CML is most readily confirmed using consensus primers to the
      framework 3 region; (2) somatic mutation is uncommon; and (3) B lymphoid clones
      distinct from those identified later may be detected before overt lymphoid BT.
      The identification of such 'abortive' clones is evidence for clonal instability
      before the onset of transformation and might have prognostic value.

PMID- 9009081
TI  - Clonality analysis of hematopoietic cell lineages in acute myeloid leukemia and
      translocation (8;21): only myeloid cells are part of the malignant clone.
AB  - Bone marrow from six patients with acute myeloid leukemia (AML) and t(8;21)
      (q22;q22) or a variant t(8;13;21) was studied by simultaneous analysis of cell
      morphology and karyotype. Combination of May-Grunwald-Giemsa (MGG) and
      fluorescence in situ hybridization (FISH) using probes specific for the
      breakpoint regions of chromosome 8 and 21 allowed us to establish the extent of
      cell-lineage involvement of the translocation. The translocation was found in all
      myeloid blasts and in high percentages of the more mature neutrophilic cells. In
      one patient we could demonstrate the translocation in the eosinophils as well.
      Erythroblasts and lymphocytes did not show the t(8;21) abnormality. These results
      indicate that the t(8;21) in AML is restricted to the myeloid (granulocytic)
      lineage.

PMID- 9009082
TI  - Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia
      with a low blast count.
AB  - To evaluate diagnostic criteria, disease characteristics, and the clinical course
      of pediatric myelodysplastic syndrome (MDS), we reviewed 327 consecutive cases
      diagnosed with de novo acute myeloid leukemia (AML) or MDS at St Jude Children's
      Research Hospital between February 1980 and January 1993. Among 49 cases with
      <30% marrow blasts (consistent with FAB criteria and common diagnostic practice
      for MDS), eight had karyotypes associated with de novo AML (four with
      t(8;21)(q22;q22) and one each with inv(16)(p13q22), t(11;17)(q23;q21),
      t(9;11)(p22;q13), and i(1)(ql0)). We termed these cases AML with a low blast
      count (AML-LBC) and compared their clinical and morphologic features with those
      of the remaining 41 cases. AML-LBC cases had little or no hematopoietic
      dysplasia. MDS cases consisted of refractory anemia (RA, n=6), RA with ring
      sideroblasts (n=2), RA with excess blasts (RAEB, n=4), RAEB in transformation
      (n=14), and chronic myelomonocytic leukemia (n=15). Most had moderate/severe or
      multilineage hematopoietic dysplasia, with significantly higher dysplasia scores
      than AML-LBC cases (P=0.007). Only 30% of patients with MDS achieved complete
      remission (CR) after two cycles of AML-directed therapy, compared with 88% of
      patients with AML-LBC (P=0.0001); MDS patients tended to experience prolonged
      severe cytopenias with chemotherapy. The 4-year survival for MDS patients was 23%
      +/- 7% (s.e.), vs 50% +/- 18% (s.e.) for AML-LBC (P=0.048). AML-LBC patients
      frequently had chloromas; none were seen in MDS patients. We conclude that the
      30% blast threshold is ineffective for separation of AML and MDS in pediatric
      patients, and that genetic data should be included in this decision process. AML
      LBC, defined by <30% blasts in bone marrow and cyto- (or molecular) genetic
      abnormalities associated with de novo AML, and characterized by absent or mild
      marrow dysplasia, is biologically and clinically distinct from MDS and should be
      treated as de novo AML. Outcome in pediatric MDS remains poor, and new treatment
      strategies are needed for these patients.

PMID- 9009083
TI  - Expression of the Zn finger gene, EVI-1, in acute promyelocytic leukemia.
AB  - The EVI-1 gene encodes a Zn finger, DNA binding protein previously detected in
      some acute myelogenous leukemias (AML) and myelodysplasias (MDS), but not in
      normal marrow or cord blood cells. Experimental studies suggest EVI-1 blocks
      cellular differentiation by binding to GATA-1 or other specific DNA sequences
      controlling gene expression, and may be involved in the pathogenesis of some
      AMLs. To further define potential roles for EVI-1 in leukemia pathogenesis, we
      studied its regulation in acute promyelocytic leukemias (APL). Seven of 11 APL
      cases expressed EVI-1 RNA detected by RNA PCR at diagnosis, and expression was
      detected in two additional cases after treatment with all-trans retinoic acid
      (ATRA). Two of four cases studied at relapse also expressed EVI-1 RNA. To
      investigate regulation of EVI-1 expression in APL, we examined its expression in
      the NB4 APL cell line. NB4 cells did not express EVI-1 under basal conditions,
      but expressed EVI-1 after ATRA-induced differentiation. When NB4 cells were
      exposed to ATRA and transferred to cultures with N,N'-hexamethylene-bis-acetamide
      (HMBA), differentiation occurred but EVI-1 RNA was not detected, indicating that
      EVI-1 expression was not required for terminal, NB4 differentiation. ATRA
      resistant NB4 cells were obtained by continuous culture in gradually increasing
      concentrations of ATRA. These cells did not express markers of differentiation
      but continued to express EVI-1 for several weeks even after ATRA withdrawal. To
      assess whether expression of the APL PML-RAR alpha fusion gene alone was
      sufficient for ATRA induction of EVI-1, the PML-RAR alpha gene cDNA was expressed
      in U937 histiocytic lymphoma cells. ATRA treatment of PML-RAR alpha-transfected
      or control U937 cells did not induce EVI-1 expression. In conclusion, this study
      demonstrates the EVI-1 gene is consistently expressed in APL cells either
      constitutively or after ATRA treatment. ATRA represents the first biologically
      active agent shown to specifically regulate EVI-1 expression in blood cells. In
      contrast to previous studies in AML and MDS, the pattern of EVI-1 expression
      suggests it may facilitate rather than inhibit myeloid differentiation during
      ATRA treatment. However, effects of EVI-1 expression are likely to be complex,
      and expression in ATRA-resistant APL cells may indicate multiple roles for this
      gene.

PMID- 9009084
TI  - Potentiation of VD-induced monocytic leukemia cell differentiation by retinoids
      involves both RAR and RXR signaling pathways.
AB  - Retinoids and vitamin D (VD) cooperate to induce the differentiation and inhibit
      the proliferation of human myelomonocytic leukemia cells. Two classes of
      retinoids receptors, the RARs and RXRs, respectively, can mediate these effects.
      RXR forms heterodimers with a variety of nuclear receptors, including RAR and the
      VD receptor. We have previously found that VD treatment increases RXR alpha
      levels in myelomonocytic leukemia cells. By immunoanalysis, we observed in the
      present work that the RAR alpha protein is expressed in proliferating U937, HL-60
      and THP-1 human leukemia cells and that VD treatment induces alterations of its
      electrophoretic pattern, although with large differences between cell lines. In
      the three cell lines, 9-cis RA, an agonist of both RARs and RXRs, cooperated with
      VD more efficiently than all-trans RA and RAR-specific synthetic ligands, thus
      suggesting an involvement of both RAR and RXR pathways in cell differentiation.
      Using U937 cells as a model, we delineated the relative contributions of RAR and
      RXR by assessing the effects of receptor-selective synthetic retinoids. The
      synergy between VD and all-trans RA or RAR-specific agonists (TTNPB and Ro 40
      6055) was abrogated by a RAR alpha-specific antagonist (Ro 41-5253), confirming
      an involvement of RAR alpha. However, the cooperation between VD and 9-cis RA,
      although reduced, was not suppressed by the antagonist, suggesting also an
      involvement of the RXR pathway. The role of RXR as a ligand-activated receptor
      was confirmed using RXR-specific agonists (CD2608 and LGD1069), which also proved
      able to cooperate with VD. Finally, while each synthetic agonist alone was
      significantly less potent than 9-cis RA, combinations of the RAR and RXR
      selective agonists TTNPB and LGD1069 appeared to be as effective as the pan
      agonist 9-cis-RA. These results confirm that various retinoids can cooperate with
      VD and demonstrate that, at a whole cell level, optimal effects require the
      activation of both RAR and RXR receptors.

PMID- 9009085
TI  - Delineation of a 6 cM commonly deleted region in childhood acute lymphoblastic
      leukemia on the 6q chromosomal arm.
AB  - Deletion of the long arm of human chromosome 6 in acute lymphoblastic leukemia
      (ALL) has been shown by cytogenetic studies in 4-11% of cases. To characterize
      further the region of deletion and to precisely establish its frequency, we
      studied loss of heterozygosity (LOH) in 120 children with ALL using polymorphic
      markers located from the 6q14-15 chromosomal band to the telomere. LOH was
      detected in eight patients. A single region of LOH, flanked distally by D6S1594
      and proximally by D6S301 was detected. These DNA markers are separated by 6 cM
      and are approximately located at the 6q21-22 band. Our present results delineate
      a region that is likely to contain a tumor-suppressor gene involved in a subset
      of childhood ALLs.

PMID- 9009086
TI  - The commonly deleted region at 9p21-22 in lymphoblastic leukemias spans at least
      400 kb and includes p16 but not p15 or the IFN gene cluster.
AB  - Chromosome band 9p21-22 is one of the most common targets for deletions in
      cancer. The p16 tumor suppressor gene maps to this region and is inactivated in a
      wide variety of tumor cell lines and primary tumors. However, in some of the
      neoplasms with frequent 9p21 loss of heterozygosity (LOH), a structurally and
      functionally normal p16 is found suggesting that this gene might not be the
      primary or only target for inactivation. To define the smallest region of overlap
      of deletions at chromosome band 9p21-22 and to clarify the involvement of p16,
      p15 and the IFN cluster gene in lymphoblastic leukemias, we used a multiplex
      polymerase chain reaction to construct a detailed map of deletions at 9p21-22. We
      studied DNA from 30 lymphoblastic leukemia patients and nine cell lines using 10
      genes/markers that map to this region, including four STS markers located between
      p16 and D9S171 (STS1, STS2) or between p16 and IFNalpha (STS3, STS4). We found
      that the size of the deletions in this region is variable and that the commonly
      deleted region spans at least 400 kb; it includes the p16 gene but excludes the
      IFN gene cluster and the p15 gene. The identification of this commonly deleted
      region enables a more focused search for other putative tumor suppressor gene at
      9p21 which could be relevant to leukemogenesis.

PMID- 9009087
TI  - A fraction unresponsive to growth inhibition by TGF-beta among the high
      proliferative potential progenitor cells in bone marrow of p53-deficient mice.
AB  - Transforming growth factor-beta (TGF-beta) has been found to block the
      progression of the cell-cycle by up-regulating a Cdk inhibitor, p15, only in
      epithelial cells; on the other hand, wild-type p53 was shown to activate
      transcriptionally the gene for another Cdk inhibitor, p21. The regulatory effects
      of TGF-beta on hematopoietic tissues is poorly understood. Hence, we investigated
      the effect of TGF-beta on hematopoietic progenitor cells in p53-deficient mice to
      determine whether an inhibitory signal from TGF-beta is linked to p53 in
      hematopoietic regulation. We found that the proliferation of megakaryocyte
      progenitors (CFU-Mk) in our wild-type mice was markedly inhibited by TGF-beta.
      Contrary to an earlier report, an erythroid and a granulocyte-macrophage
      progenitor, stimulated by IL-3, were not significantly inhibited, whereas TGF
      beta also completely inhibited the growth of high-proliferative potential
      progenitor cells (HPP-CFC) in the marrow of mice with 5-fluorouracil (5FU), as
      reported. It is interesting that in the p53-deficient mice, the inhibitory action
      of TGF-beta on the HPP-CFC was incompletely abolished. The response curve we
      obtained for graded doses of TGF-beta suggests that there is, at least, a
      subpopulation of HPP-CFC which is less sensitive to the regulation by TGF-beta.
      In contrast to HPP-CFC, the CFU-Mk, which TGF-beta inhibited only in wild-type
      mice not treated with 5FU, remained inhibited in the p53-deficient strain. Thus,
      HPP-CFC might be regulated by TGF-beta through their signal pathways which are
      linked to p53.

PMID- 9009088
TI  - Autocrine IL-2-dependent growth of a newly established CD3+, CD16-, CD56+, CD57+,
      J(H)-, TCRbeta-, TCRgamma- leukemia cell line (NOI-90).
AB  - Leukemic cells from a 45-year-old male patient with a CD3+, CD56+, CD57+, CD7+
      acute lymphoblastic leukemia were cultured in vitro in the absence of any added
      growth factor for up to 6 years and a continuous lymphoblastoid cell line (NOI
      90) was established. NOI-90 cells have the same phenotype and karyotype as
      initial leukemic cells. Southern blot of DNA from NOI-90 cells showed that
      TCRbeta, TCRgamma, and J(H) were in germ line. Two and 25% of NOI-90 cells were
      positive when stained with the IOT14 and 7G7/B6 moAbs, which recognize the CD25
      molecule (IL-2R alpha chain); moreover, 4% and 13% of the cells were positive
      when stained with the TU-27 and mik beta3 moAbs which recognize the CD122
      molecule (IL-2Rbeta chain). Equilibrium binding experiments with radiolabelled IL
      2 revealed the presence of a small number of high affinity IL-2R on both fresh
      and continuously growing cells. Media conditioned by NOI-90 cells could induce
      proliferation of an IL-2-dependent cell line and this IL-2 activity could be
      detected by a sensitive immunoenzymatic assay using antibodies recognizing
      distinct epitopes of IL-2. Moreover, IL-2 activity could be adsorbed by
      immunoaffinity on anti-IL-2 polyclonal purified IgG and the retained molecule
      displayed a m.w. of 14.5 kDa in SDS-PAGE. In addition, IL-2 immunoreactive
      molecules could be revealed in the cytoplasm of the cells. Finally, IL-2 fixed on
      the cell membrane could be detected by indirect immunofluorescence. Although
      added IL-2 could not induce cell proliferation, monoclonal antibodies against
      CD25, CD122 and IL-2 could specifically inhibit spontaneous cell proliferation in
      a dose-dependent manner. NOI-90 cells failed to demonstrate any cytotoxic
      activity against the K-562, Raji or Daudi cells. These findings indicate that NOI
      90 cells are of non-T, non-B, origin lacking NK activity but proliferate under an
      autocrine pathway which involves, at least partly, the IL-2/IL-2R system.

PMID- 9009089
TI  - Co-expression of several molecular mechanisms of multidrug resistance and their
      significance for paclitaxel cytotoxicity in human AML HL-60 cells.
AB  - Overexpression of P-glycoprotein (PGP), MRP or LRP has been characterized as the
      'proximal', while overexpression of the anti-apoptosis Bcl-2 or Bcl-xL relative
      to the pro-apoptosis Bax protein has been recognized as the 'distal' mechanism of
      multidrug resistance in human AML cells. In the present studies, we examined
      whether these mechanisms can co-exist in human AML HL-60 cells. We also
      determined how these mechanisms would affect the accumulation and cytotoxicity of
      a PGP substrate, such as Taxol (paclitaxel). For this, immunoblot analyses were
      performed to determine the expression of PGP, MRP, Myc, Bcl-2, Bcl-xL and Bax on
      either the multidrug-resistant HL-60 sublines created under the selection
      pressure of doxorubicin (HL-60/AR), paclitaxel (HL-60/TAX1000) or vincristine (HL
      60/VCR), or sublines created by transfection and overexpression of the bcl-2 (HL
      60/Bcl-2) or bcl-xL gene (HL-60/Bcl-xL). As compared to the control HL-60, HL
      60/AR cells possess high MRP while HL-60/TAX1000 and HL-60/VCR cells express high
      levels of the mdr-1 encoded PGP. In addition, these multidrug-resistant cells
      possess 1.5- to 2.5-fold higher Bcl-2, while their Bax and Myc levels are similar
      to those in the control HL-60 cells. HL-60/TAX1000 and HL-60/VCR cells also
      express three- and 2.5-fold higher Bcl-xL levels. PGP, but not MRP,
      overexpression significantly impaired paclitaxel accumulation and paclitaxel
      induced apoptosis, as well as reduced its cytotoxic effects as determined by the
      MTT assay. In contrast, enforced and much higher expression of Bcl-2 in HL-60/Bcl
      2 (five-fold) or Bcl-xL in HL-60/Bcl-xL cells (10-fold) significantly reduced
      paclitaxel-induced apoptosis and the loss of cell viability, without affecting
      its intracellular accumulation. These results confirm the possibility of co
      expression of multiple mechanisms of multidrug resistance in human leukemic cells
      which had been selected by exposure to a single drug. The results also indicate
      that MRP overexpression does not confer resistance against paclitaxel. In
      addition, these findings suggest that, for Bcl-2 and Bcl-xL, enforced
      overexpression to high levels is necessary to induce paclitaxel resistance in HL
      60 cells.

PMID- 9009090
TI  - Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B
      cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis.
AB  - Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine which has
      recently been shown to delay fludarabine-induced apoptosis in B cell chronic
      lymphocytic leukemia (B-CLL) cells. To investigate the potential mechanism of
      bFGF-mediated delay of apoptosis, two EBV-transformed B prolymphocytic cell lines
      (JVM-2, JVM-13), one EBV-transformed B-CLL cell line (I83CLL), and one non-EBV
      transformed B-CLL cell line (WSU-CLL) were used as a model for chronic lymphoid
      malignancies. Viability data of cells treated with fludarabine alone or in
      combination with bFGF demonstrated that the addition of bFGF to the cells
      resulted in prolonged survival. Quantitative assessment of apoptosis-associated
      DNA strand breaks by in situ TdT labeling showed a protective effect of bFGF on
      fludarabine-treated cells. The potential effect of bFGF on bcl-2 mRNA expression
      was analyzed by Northern blotting. Stimulation with bFGF led to a time-dependent
      accumulation of bcl-2 specific mRNA in all three cell lines. Maximal levels of
      bcl-2 mRNA expression were detected after 8 h in JVM-2, and after 18 h in JVM-13
      and I83CLL. Intracellular bcl-2 protein was also found to be increased upon bFGF
      stimulation in both EBV- and non-EBV-transformed cells. In addition, exposure of
      cells from three patients with B-CLL to bFGF showed an upregulation of bcl-2
      protein after 4-8 h. Our data demonstrate that bFGF upregulates the expression of
      bcl-2 in these cells, suggesting that this increase in bcl-2 expression may play
      a role in the delay of fludarabine-induced apoptosis.

PMID- 9009091
TI  - Human herpes virus 8 (Kaposi's sarcoma herpes virus) and malignant
      lymphoproliferations in France: a molecular study of 250 cases including two AIDS
      associated body cavity based lymphomas.
AB  - The new human herpes virus 8 (HHV8) was recently detected in cases of body cavity
      based lymphoma (BCBL), a rare B cell lymphoma, mostly AIDS-associated. We
      investigated for HHV8 DNA sequences a series of 250 B or T cell
      lymphoproliferative malignancies, as seen in France, including 126 leukemias and
      124 lymphomas (232 non-AIDS-associated and 18 AIDS-associated tumors). HHV8
      sequences were detected in only three patients. The first two were homosexual
      males, HIV-infected since 1985 who suffered from a BCBL initially characterized
      in one case by a pleural lymphomatous effusion and a peritoneal one in the other
      case. A high level of HHV8 copies was detected in the tumoral cells of these two
      BCBL. In contrast, in the third positive patient who had an AIDS-associated
      immunoblastic lymphoma, the HHV8 sequences level was quite low. In the two BCBL
      patients, the HHV8-infected clonal B cells had a large immunoblastic feature with
      an indeterminate phenotype and were also infected by Epstein-Barr virus. In one
      BCBL case, a semiquantitative PCR analysis revealed that the HHV8 sequences were
      much more abundant in the effusion tumor cells than in the cutaneous Kaposi's
      biopsy while no HHV8 sequence was detectable in the peripheral blood lymphocytes.
      This study reports HHV8-associated BCBL in European AIDS patients and confirms
      that HHV8 is present at a high copy number in the tumoral B cells of this
      malignancy. Furthermore, HHV8 does not seem to play a pathogenic role in any of
      the other T or B malignant lymphoid neoplasias studied so far. This study also
      stresses the necessity for quantification studies in interpretation of a positive
      PCR analysis for HHV8 sequences, especially in patients at risk for HIV infection
      or Kaposi's sarcoma.

PMID- 9009092
TI  - NF-E2p18/mafK is required in DMSO-induced differentiation of Friend
      erythroleukemia cells by enhancing NF-E2 activity.
AB  - When Friend murine erythroleukemia (F-MEL) cells are induced to differentiate by
      dimethylsulfoxide (DMSO), erythroid-specific genes are transcriptionally
      activated. The erythroid transcription factor NF-E2 is essential for enhancer
      activity of the globin locus control regions. NF-E2 functions as a heterocomplex
      consisting of a 45-kDa subunit (NF-E2p45) and a 18-kDa subunit (NF-E2p18). The
      larger subunit NF-E2p45 is tissue-restricted and is believed to play a role in
      globin gene expression in F-MEL cells. The expression of the smaller subunit NF
      E2p18, which is a Maf family member (MafK), is cell type- and developmental stage
      specific. We have investigated the possible role of NF-E2p18 in Friend erythroid
      differentiation by stably transfecting either sense and antisense p18 constructs
      into differentiation-sensitive 745A and partially defective-differentiation TFP10
      cell lines. Overexpression of NF-E2p18 induced expression of globin transcripts
      in both cell lines and increased their sensitivity to erythroid differentiation
      when exposed to DMSO. Conversely, inhibition of p18 expression by antisense
      transcripts resulted in the inhibition of DMSO-induced differentiation in both
      cell lines. These results indicate that NF-E2p18 is necessary for globin
      expression in F-MEL cells and that it is the predominant gene of the Maf family
      involved in DMSO-induced erythroid differentiation. Moreover F-MEL clones
      overexpressing NF-E2p18 showed an increase in specific NF-E2 DNA-binding activity
      whereas this activity was decreased in clones expressing antisense p18. Finally,
      studies using transient transfection assays showed that p18 activated NF-E2 site
      dependent transcription in F-MEL cells. These data suggest that NF-E2p18 can
      participate in DMSO-induced erythroid differentiation of F-MEL cells by enhancing
      NF-E2 activity.

PMID- 9009093
TI  - Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow
      transplantation (BMT): evidence for a graft-versus-myeloma effect.
AB  - Adoptive immunotherapy with donor-derived buffy coat cells for relapsed
      hematological malignancies after allogeneic BMT is an established and highly
      effective treatment. We report a patient who relapsed on day +330 after
      allogeneic sibling BMT for multiple myeloma with multiple solid subcutaneous
      tumors consisting of plasma cells. Histology and immunocytology of the bone
      marrow did not show plasma cell infiltration. After cessation of the
      immunosuppression consisting of cyclosporine and methylprednisolone, a total of
      6.2 x 10(7)/kg recipient body weight CD3+ T cells derived from the donor by
      leukapheresis were transfused on 4 consecutive days. To enhance the T cell effect
      six doses of 5 million units alpha interferon were given subcutaneously. Five
      days later the tumors started to shrink and have completely vanished since day
      x400 after BMT. The patient developed acute GVHD grade III of the liver and gut
      which was treated by reinduction of various immunosuppressive drugs. Up to now
      there is no evidence for relapse of the multiple myeloma, but the patient suffers
      from extensive chronic GVHD (gut and liver). This is the first report to
      demonstrate a graft-versus-myeloma effect for relapse with solid tumor
      manifestation after sibling BMT with donor-derived buffy coat cells as adoptive
      immunotherapy.

PMID- 9009094
TI  - Establishment and characterization of a human stroma-dependent myeloma cell line
      (MM5.1) and its stroma-independent variant (MM5.2).
AB  - Although IL-6 has been identified as a major growth factor in multiple myeloma
      (MM), it is believed that maintenance of tumor growth in vivo depends on one or
      more additional stroma-derived factors. We describe a new human myeloma cell line
      (MM5.1) that can be maintained in the presence of bone marrow-derived stromal
      cell layers, and not only when cultured with exogeneous IL-6. This cell line
      expresses the same immunoglobulin kappa light chain RNA sequence as the patient's
      original tumor cells, has a plasma cell morphology and expresses plasma cell
      antigens (cytoplasmic kappa light chain, CD38, BB4). Without the presence of
      stromal factors, MM5.1 cells become apoptotic. A low proliferative effect was
      observed in the presence of oncostatin M (OSM) but other cytokines (IL-10, IL-11,
      stem cell factor (SCF) and leukemia inhibitory factor (LIF)) had no effect at
      all. We observed that MM5.1 cells also grow when physically separated from
      stromal cell layers by a 0.45 microm microporous membrane or when cultured in
      conditioned medium from stromal marrow cells. Unexpectedly, the growth in stromal
      supernatants was markedly inhibited by an anti-IL-6 antiserum and an anti-IL-6
      receptor transducer chain (gp130) mAb in a dose-dependent manner. This implies
      that MM5.1 cells are IL-6 responsive only when exposed to one or more additional
      soluble factor(s) derived from bone marrow stroma. Coculturing MM5.1 cells with
      IL-6 and cytokines that were described to increase the IL-6 responsiveness of
      myeloma cells (G-CSF, GM-CSF and IL-3) had no effect on the growth or survival. A
      strong proliferative effect was observed when MM5.1 cells were cultured with IL-6
      and soluble IL-6 receptor (sgp80). However no sgp80 could be detected in stromal
      supernatants using a sensitive immunoassay. This indicates that sustained
      proliferation of the MM5.1 cell line depends on a combination of IL6 and at least
      one, thus far unidentified, stroma-derived factor. After more than 1 year in
      continuous culture, we could obtain a variant of the line (MM5.2) that shows an
      improved growth rate and grows stroma independently. Molecular analysis revealed
      clonal identity with the early passage form and Epstein-Barr virus antigen
      expression was negative. The two variants of this cell line offer a useful model
      to identify molecular mechanisms involved in clonal evolution towards stroma
      independent growth of myeloma cells.

PMID- 9009095
TI  - Good correlation between RT-PCR analysis and relapse in Philadelphia (Ph1)
      positive acute lymphoblastic leukemia (ALL).
AB  - We sequentially performed cytogenetic analysis and RT-PCR analysis of BCR-ABL
      transcripts in 17 cases of Ph1-positive ALL who had achieved hematological
      complete remission (CR) with intensive chemotherapy (CT). Sixteen cases were
      studied prospectively. All but one of the patients had reached cytogenetic CR,
      but cytogenetic has low sensitivity in predicting relapse. Twelve patients
      relapsed, three died in first CR and two were alive in first CR. Two of five, two
      of four, and five of nine patients who were allografted (in first or second CR),
      autografted and received consolidation CT, respectively, achieved negative two
      round PCR in the bone marrow (BM): three died in CR, three remained in CR with
      negative two-step PCR in the BM and three relapsed after 22 to 28 months. In all
      cases, relapse was preceded by switch to PCR positivity in the BM by 4 to 6
      months. The remaining nine patients remained PCR-positive in the BM and relapsed
      after 2 to 16 months. In the four autografted cases, PCR was positive at the time
      of bone marrow harvest. The two patients who received a purged transplant
      achieved negative PCR and prolonged CR, whereas the two patients who received an
      unpurged transplant remained PCR positive and relapsed. In 34% of the samples
      where analysis was concomitant, sensitivity of PCR proved lower in the blood than
      in the BM. These findings show that RT-PCR is a useful tool in the monitoring of
      MRD in Ph1 positive ALL.

PMID- 9009096
TI  - Loss of the DEK-CAN fusion transcript in a child with t(6;9) acute myeloid
      leukemia following chemotherapy and allogeneic bone marrow transplantation.

PMID- 9009097
TI  - Molecular analysis of hematopoietic colonies derived from chronic myeloid
      leukemia patients: interphase fluorescence in situ hybridization compared with RT
      PCR.
AB  - In this study we compared interphase fluorescence in situ hybridization (I-FISH)
      with reverse transcription polymerase chain reaction (RT-PCR) for the molecular
      analysis of hematopoietic colonies derived from patients with chronic myeloid
      leukemia (CML). Molecular analysis of individual colonies is often performed to
      monitor purging efficacy in CML. We harvested individual colony-forming unit
      granulocyte-macrophage (CFU-GM) colonies. One half was analyzed with I-FISH, for
      the presence of bcr-abl fusion gene. The other half was analyzed with RT-PCR for
      the presence of the bcr-abl mRNA. We wanted to address the following questions:
      (1) is the bcr-abl gene always expressed in CFU-GM colonies and (2) which
      technique has to be preferred to analyze individual CFU-GM colonies? In total,
      133 colonies, derived from six CML patients, could be analyzed both with I-FISH
      and RT-PCR. We found a positive correlation in 89% of the cases: 118 colonies
      showed the same results with both techniques. However, 15 of the 106 I-FISH
      positive colonies were negative in the RT-PCR. Serial analysis of the cDNA
      derived from 22 colonies showed in each round of amplification 21-29% RT-PCR
      negative but I-FISH-positive colonies. However, all I-FISH-positive colonies
      showed at least one positive RT-PCR, either in the first, second or third round
      of amplification. These results indicate that the bcr-abl gene is probably always
      transcriptionally active in CFU-GM colonies. Reliable analysis with RT-PCR is
      possible but likely to generate false negative results. We conclude that: (1) I
      FISH offers a reliable alternative to RT-PCR for analyzing individual
      hematopoietic colonies and (2) results obtained with RT-PCR should only be
      interpreted with caution.

PMID- 9009098
TI  - Evidence for the embryonic origin of partial chromosome 7 deletion in monozygotic
      twins with juvenile chronic myelogenous leukemia.
AB  - During donor evaluation for allogeneic bone marrow transplantation (BMT) of a 28
      month-old child with juvenile chronic myelogeneous leukemia (JCML) with 46,XY,
      7,+mar karyotype, the potential donor twin brother was found to be
      thrombocytopenic. Subsequent genotype analysis determined monozygosity with 98%
      probability. Bone marrow analysis of the twin brother revealed the same 46,XY,
      7,+mar karyotype and a diagnosis of JCML was made. Metaphase FISH studies
      documented that mar chromosome in both twins contains the pericentromeric region
      of chromosome 7 and thus both twins had a partial monosomy of chromosome 7. A
      possible embryonic origin of del(7) is proposed.

PMID- 9009099
TI  - Concentrations of serum leukemia inhibitory factor (LIF) in patients with
      hematologic malignancies.

PMID- 9009100
TI  - Differential adhesion of metastatic RAW117 large-cell lymphoma cells under static
      or hydrodynamic conditions: role of integrin alpha(v) beta3.
AB  - RGD-containing substrates were used to study static and hydrodynamic adhesion of
      murine RAW117 large-cell lymphoma sublines with differential liver-metastatic
      potentials. Highly liver-metastatic RAW117-H10 cells had higher rates of static
      adhesion to vitronectin, fibronectin and (GRGDS)4 than poorly metastatic RAW117-P
      and moderately liver-metastatic RAW117-L17 cells. Under hydrodynamic conditions,
      adhesion stabilization was more rapid for H10 cells compared to P or L17 cells.
      Among the RGD peptides, only the polymeric RGD peptide (GRGDS)4 mediated strong
      static adhesion of H10 cells. Interestingly, all the RGD peptides mediated
      adhesion stabilization for H10 cells but still not for L17 or P cells under
      hydrodynamic conditions. Integrin alpha(v) beta3 was involved in stabilizing
      hydrodynamic adhesion to (GRGDS)4, monomeric RGD peptide R1, but was less
      important in static adhesion to monomeric RGD peptides. Differential adhesion to
      liver sinusoidal endothelial cell-derived extracellular matrix (H10 >> L17 > P)
      was observed under hydrodynamic but not static conditions. Integrin alpha(v)
      beta3 was also important in hydrodynamic adhesion to liver sinusoidal endothelial
      cell-derived extracellular matrix. We believe that strong static and hydrodynamic
      adhesion of H10 cells and their capability of altering adhesive behavior in
      response to fluid shear may contribute to liver metastasis.

PMID- 9009101
TI  - Effects of ionizing radiation on the adhesive interaction of human tumor and
      endothelial cells in vitro.
AB  - A centrifugation assay was used to determine the effects of ionizing radiation on
      the adhesive interaction of A549 human lung adenocarcinoma tumor cells and human
      umbilical vein endothelial cells (HUVEC). The tumor cells were fluorescently
      labeled and divided into control (sham-irradiated) and irradiated groups. The
      irradiated groups were exposed to irradiation levels ranging from 5 to 20 Gy
      using a 137Cs source. A specified number of these A549 tumor cells were then
      delivered into each well of 96-well cell culture plates containing confluent
      monolayers of human umbilical cord vein endothelial cells (HUVEC), and were given
      time to adhere to the endothelial cells. The wells were then sealed and were
      exposed to an acceleration field varying from 1 to 42 g (0-500 rpm) for 10 min.
      Finally, the wells were drained, and the number of tumor cells adhering to the
      endothelial monolayer were counted using a fluorescent microscope system. Our
      results indicate that the irradiation of A549 tumor cells significantly increased
      their adhesive interaction with endothelial cells (number of adhering irradiated
      cells/number of adhering control cells = 1.0, 1.3, 1.9, 2.2 for 0, 5, 10, 20 Gy
      respectively). In contrast, when endothelial cells were irradiated, rather than
      tumor cells, adhesive interaction decreased with an increase in the radiation
      dose (irradiated/control = 1.0, 0.9, 0. 8, 0.5 for 0, 5, 10, 20 Gy respectively).
      Simultaneous irradiation of both the tumor cells and the endothelial cells did
      not alter their adhesive interaction significantly. These findings may have
      important implications for the metastatic ability of irradiated tumor cells.

PMID- 9009102
TI  - Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity
      of murine tumor cells and correlation with cathepsin (L + B) secretion.
AB  - Cells in tumors may be exposed to adverse conditions such as nutrient
      deprivation, acidic pH and hypoxia. It has been shown previously that exposure to
      hypoxia, acidosis and glucose starvation in vitro increases the experimental
      metastatic ability of murine KHT-LP1 sarcoma, SCC-VII squamous carcinoma and B16
      melanoma cells. This effect was most marked when cells were allowed to recover
      under normal in vitro growth conditions before injection. In the present study we
      examined whether the invasive capacity of the cells could be influenced by these
      modifications of the cell microenvironment. We used Matrigel, a basement membrane
      like preparation in a two-chamber invasion assay to address this issue. Both KHT
      LP1 and SCC-VII murine cell lines showed an increased ability to invade through
      Matrigel after hypoxia, and glucose starvation, but there was no consistent
      change in invasive capacity following acidosis exposure. The results for hypoxia
      and glucose starvation are in agreement with our previous studies of metastatic
      ability for these cell lines and we confirmed this for KHT-LP1 cells exposed to
      hypoxia in the current study. In parallel with the invasion assays, we compared
      cathepsin (L + B) content of the cells in treated and control suspensions. The
      effect observed varied according to the cell line and the treatment received
      (hypoxia, glucose starvation). There was an increase of cathepsin content for KHT
      LP1 cells exposed to hypoxia and this increase correlated well with the increase
      of the invasion ability through Matrigel. We did not observe any increase of
      cathepsin for hypoxia-treated SCC-VII or for KHT-LP1 and SCC-VII cells treated
      with glucose starvation. These results suggest that transient hypoxia and glucose
      starvation can increase the invasive ability of tumor cell lines and thus may
      cause tumor progression by facilitating the invasive step of the metastatic
      process. The increased levels of cathepsin (L + B) in the KHT-LP1 cells treated
      with hypoxia, compared to control non-treated cells, may play a part in this
      increased invasive capacity.

PMID- 9009103
TI  - Evaluation of fluorometric and zymographic methods as activity assays for
      stromelysins and gelatinases.
AB  - To measure matrix metalloproteinase (MMP) activity in a large number of samples
      it is advisable to use easily automated methods. We have evaluated and compared
      the activity of stromelysin-1 (MMP-3), matrilysin (MMP-7), 72 kDa gelatinase A
      (MMP-2) and 92 kDa gelatinase B (MMP-9) by zymogram analysis and fluorescent
      substrate degradation assays. FITC-casein and the fluorogenic peptide Dnp-Pro
      beta-cyclo-hexyl-Ala-Gly-Cys(Me)-His-Ala-Lys-(N-Me-Abz)-NH 2 were used as
      fluorescent substrates. FITC-casein was more efficiently degraded than the
      fluorogenic peptide by all MMPs tested except MMP-9. MMP-2 was not significantly
      able to degrade the fluorogenic peptide. Gelatin zymography was the most
      sensitive method to detect the activity of both gelatinases but quantitation
      problems compromise its use. The degradation of fluorogenic substrates by MMPs
      could be inhibited by the chelating agent EDTA and by the tissue inhibitor of
      metalloproteinases 2 (TIMP-2), an MMP-specific inhibitor. Fluorometric methods
      represent a good alternative for MMP activity measurement, especially when a
      large number of samples must be processed.

PMID- 9009104
TI  - Effects of neuroblastoma tumor gangliosides on platelet adhesion to collagen.
AB  - Gangliosides, sialic acid-containing glycosphingolipids, enhance tumor formation
      in experimental animals and are associated with tumor progression and metastasis
      in humans. The mechanism(s) for this activity is (are) unknown. One possibility
      is enhanced platelet activation, since the interaction of platelets with tumor
      cells contributes to tumor cell arrest in the vascular compartment. We have
      previously shown that neuroblastoma tumor gangliosides (NBTG) enhance platelet
      adenosine triphosphate (ATP) secretion, aggregation, and adhesion. We determined
      that these NBTG effects are specific for collagen and are mediated through an
      alpha2 beta1 integrin-dependent mechanism. This report describes the effects of
      NBTG on a physiologically relevant model of collagen-alpha2 betal interaction.
      Platelet adhesion to immobilized native collagen fibers similar to those found in
      the extracellular matrix of blood vessels was determined. Platelet adhesion is
      enhanced by NBTG in a concentration-dependent manner. Incubation with
      concentrations of 1 and 10 microM NBTG increased platelet adhesion by 9% and 52%,
      respectively, compared to less than 1% in controls not incubated with
      gangliosides (P = 0.001 and P < 0.0001, respectively). In addition to increasing
      the number of adherent platelets, NBTG promoted more rapid attachment. In NBTG
      incubated platelets, platelet adhesion began after a 5-min lag phase and was
      maximal at 30 min compared to a 20-min lag phase and maximal adhesion at 60 min
      for control platelets. At 30 min this difference was significant (P = 0.017);
      however, by 120 min there was no difference between NBTG and controls (P =
      0.259). NBTG also induces platelet adhesion at collagen concentrations (0.1
      microg) that failed to support adhesion of control platelets. These effects of
      NBTG require Mg2+ or Mn2+ ions but are not supported by Zn2+ or Ca2+ ions.
      Furthermore, preincubation of platelets with a blocking antibody (6F1) to the
      integrin collagen receptor alpha2 beta1 abrogates all of the effects of NBTG.
      These results indicate that tumor gangliosides enhance platelet adhesion to
      extracellular matrix collagen and promote rapid stabilization of the collagen
      alpha2 beta1 interaction, the initial steps in platelet activation.

PMID- 9009105
TI  - Transforming growth factor beta upregulates the integrin-mediated adhesion of
      human prostatic carcinoma cells to type I collagen.
AB  - Prostate cancer frequently metastasizes to bone, and we propose that this process
      may be facilitated by the adhesion of metastatic cells to bone-derived type I
      collagen. We examined collagen receptor function and regulation in osteotropic PC
      3 human prostatic carcinoma cells. PC-3 cell adhesion to immobilized human type I
      collagen was promoted by Mn2+ and Mg2+ ions and was RGD-independent. Antibodies
      directed against beta1 or alpha2 integrin subunits inhibited adhesion to collagen
      by 90% and 53%, respectively, suggesting involvement of the alpha2 beta1
      receptor. Anti-alpha1 or anti-alpha3 antibodies had no effect on adhesion. Flow
      cytometry and immunoprecipitation of [35S]methionine-labeled cells demonstrated
      that alpha2 beta1 was the major collagen receptor expressed by PC-3 cells. The
      pretreatment of PC-3 cells with transforming growth factor-beta1 (TGF-beta1), a
      major bone-derived growth factor, caused a rapid (2 h) 2-fold increase in the de
      novo synthesis of alpha2 and beta1 integrin subunits, and also increased by 2- to
      3-fold the adhesion and spreading of PC-3 cells on collagen. We conclude that
      alpha2 beta1 is the major collagen receptor employed by PC-3 cells, and that
      alpha2 beta1 upregulation by TGF-beta is associated with an increased adhesion
      and spreading on collagen. The data suggest that exposure of metastatic PC-3
      cells to the high levels of TGF-beta in bone may promote their ability to adhere
      to bone-derived collagen, which may thereby facilitate the localization of
      metastatic cells in the skeleton.

PMID- 9009107
TI  - Mathematical modelling of cancer invasion and metastasis: an interdisciplinary
      workshop held at the University of Warwick, Coventry, UK. 11-13 September 1996.

PMID- 9009106
TI  - Assessment of the invasive potential of human gynecological tumor cell lines with
      the in vitro Boyden chamber assay: influences of the ability of cells to migrate
      through the filter membrane.
AB  - The Boyden chamber assay is widely used for in vitro measurement of the invasive
      capacity of cells. However, results can be affected significantly if certain
      precautions are not taken. Using the Boyden chamber assay we investigated in
      vitro the invasive potential of a variety of human gynecological tumor cell lines
      to degrade and migrate through the artificial basement membrane matrix Matrigel.
      However, in the absence of this Matrigel layer large differences were observed in
      the ability of cells to adhere to, migrate through and attach to the lower side
      of the filter membranes. These differences were influenced by cell density,
      degree of directional locomotion, and the size of the filter pores. To adjust for
      these influences (which are not directly correlated to the capacity of cells to
      traverse the Matrigel layer), invasion results were corrected for the ability of
      cells to migrate through the filter membrane. In addition, the invasion of MDA-MB
      231 cells was used as an internal standard to compensate for variations in the
      Matrigel layer between different experiments. Overall, in our experimental set
      up, the five human breast cancer cell lines were the most invasive (mean invasion
      +/- SEM relative to MDA-MB-231 invasion: 104.7 +/- 6.1%), the five human ovarian
      cancer cell lines the least invasive (60.2 +/- 2.2%) and the six human
      endometrial cancer cell lines showed an intermediate capacity (79.1 +/- 3.5%). In
      conclusion, the Boyden chamber assay can be used reliably for studying the
      invasive potential of cells in vitro, if the ability of the cells to migrate
      through the filter is taken into account, and a reference cell line is included
      to enable comparison of the data obtained from independently performed
      experiments on different cell lines.

PMID- 9009108
TI  - Validation of polyethylene glycol 3350 as a poorly absorbable marker for
      intestinal perfusion studies.
AB  - Polyethylene glycol (PEG) has been used as a poorly absorbable marker in
      intestinal perfusion studies, but there is controversy about the absorbability of
      PEG, particularly when glucose-sodium cotransport is occurring. Total intestinal
      perfusion studies were done in five normal humans using three solutions
      containing 1 g/liter PEG 3350 and designed to produce low rates of water
      absorption, high rates of water absorption, or high rates of glucose-sodium
      cotransport. Water absorption rates were calculated by traditional nonabsorbable
      marker equations and by a novel balance technique in which absorption was taken
      as the difference between the volumes of solution infused and recovered during
      steady-state conditions. Effluent PEG recovery was 99 +/- 4%, 109 +/- 2%, and 104
      +/- 6% of the amount infused with each solution. Water absorption rates measured
      by use of PEG concentrations were similar to those calculated by the balance
      technique (r = 0.99). The complete recovery of PEG confirms the poor
      absorbability of PEG 3350, and the excellent agreement between techniques
      validates PEG as a poorly absorbed marker, even when glucose-sodium cotransport
      is occurring.

PMID- 9009109
TI  - Treatment of metallic biliary stent-induced duodenal ulceration using endoscopic
      laser therapy.

PMID- 9009110
TI  - Comparison of scintigraphy and lactulose breath hydrogen test for assessment of
      orocecal transit: lactulose accelerates small bowel transit.
AB  - The lactulose breath test (LBT) and gastroenterocolonic scintigraphy (GECS) can
      both be used to measure orocecal transit time (OCTT). The aims of this study were
      (1) to measure OCTT by LBT and GECS and (2) to determine whether lactulose alters
      orocecal transit. METHODS: Eight normal subjects underwent simultaneous breath
      hydrogen testing, GECS, and duodenal manometry while receiving either 10 g
      lactulose or placebo with a radiolabeled solid/liquid test meal during two
      studies. There was a good correlation between OCTT by LBT and GECS when performed
      simultaneously (r = 0.95; P < 0.001). OCTT by GECS with lactulose was
      significantly faster (P = 0.004) than by GECS without lactulose, despite no
      change in gastric emptying of liquids and slowing of gastric emptying of solids
      (P = 0.02). The postprandial duodenal motility index was greater with lactulose
      than with placebo (P = 0.031). This study demonstrates that LBT and GECS (without
      lactulose) are not equivalent measures of OCTT. The standard LBT accelerates OCTT
      and slows gastric emptying. Therefore, lactulose has a direct accelerating effect
      on small intestinal transit.

PMID- 9009111
TI  - Intestinal transit is more potently inhibited by fat in the distal (ileal brake)
      than in the proximal (jejunal brake) gut.
AB  - Fat in the proximal and distal gut inhibits intestinal transit as the jejunal
      brake and the ileal brake. It is unknown, however, whether the intestinal transit
      response to fat in the proximal vs distal gut is different. Since surgical
      removal of the distal small intestine induced faster transit and greater
      steatorrhea than removal of the proximal small intestine, we hypothesized that
      the ileal brake inhibited intestinal transit more potently than the jejunal
      brake. In six dogs equipped with duodenal (10 cm from pylorus) and midintestinal
      (160 cm from pylorus) fistulas, we compared intestinal transit across an isolated
      150-cm test segment (between fistulas), while 0 (buffer), 15, 30, or 60 mM oleate
      was delivered into either the proximal (between fistulas) or the distal (beyond
      the midintestinal fistula) half of the gut. The half of the gut not receiving
      oleate was perfused with buffer. Buffer perfused into both the proximal and the
      distal half of the gut served as the control. A meal was administered and
      diverted completely out of the duodenal fistula so that the studies were all done
      in the fed state. Intestinal transit was measured by counting for the recovery of
      a radioactive marker from the temporarily diverted output of the midintestinal
      fistula. We found that (1) intestinal transit was inhibited more potently by
      oleate in the distal than in the proximal half of the gut (region effect; P <
      0.01), (2) oleate inhibited intestinal transit in a load-dependent fashion (dose
      effect; P < 0.05), and (3) load-dependent inhibition of intestinal transit by
      oleate depended on the region of exposure (interaction between load and region; P
      < 0.01). We conclude that intestinal transit is more potently inhibited by fat
      induced ileal than jejunal brake.

PMID- 9009112
TI  - Effect of cholecystokinin octapeptide and atropine on human colonic motility,
      tone, and transit.
AB  - The role of cholecystokinin (CCK) in postprandial control of colonic motility is
      controversial. To test the hypothesis that CCK stimulates colonic tone, motility,
      and transit we measured these colonic functions in 16 healthy subjects using
      intraluminal manometry, barostatic balloon measurements, and radioscintigraphy.
      This was a randomized-order, double-blind, sequential study design in each
      subject of saline and either atropine (0.01 mg/kg stat and 0.01 mg/kg/hr by
      infusion) or CCK-octapeptide (OP, 30 ng/kg stat and 60 ng/kg/hr by infusion).
      Atropine was used as control to demonstrate responsiveness of selected parameters
      of colonic motility. Atropine significantly reduced whole colon (change from
      fasting = 52 +/- 11%) and left colon (change from fasting 61 +/- 8%) phasic
      pressure activity and transverse colon tone (change from fasting 159 +/- 40%);
      CCK-OP had no significant effects on phasic contractility, tone or transit. Thus,
      a CCK-OP infusion that maximally stimulates pancreatic exocrine secretion and
      gallbladder contraction has no effect on motor function or transit in prepared
      colon of healthy subjects.

PMID- 9009113
TI  - Effect of carbonated water on gastric emptying and intragastric meal
      distribution.
AB  - Carbonated water has long been advocated to relieve dyspeptic symptoms,
      suggesting that it may alter gastric motility via gastric distension. This study
      aimed to determine the effect of carbonated water on gastric emptying of a
      radiolabeled mixed meal in eight healthy volunteers. Meal emptying and its
      distribution within the stomach were assessed with carbonated and still water in
      a crossover study. Emptying of both solid and liquid, including the duration of
      the lag phase, was identical for both drinks. However, the proximal stomach
      contained a greater proportion of solids (74 +/- 7% vs 56 +/- 8%, P < 0.05) and
      liquids (43 +/- 5% vs 27 +/- 4%, P < 0.05) with carbonated water as opposed to
      still water. Retention of the meal within the proximal stomach ended with the lag
      phase and was likely related to proximal distension. In conclusion, carbonated
      water did not alter overall gastric emptying but profoundly modified intragastric
      distribution of the meal.

PMID- 9009114
TI  - Effect of extrinsic denervation in a canine model of jejunoileal
      autotransplantation on mechanical and electrical activity of jejunal circular
      smooth muscle.
AB  - Little is known about the acute and chronic effects of the intestinal
      transplantation on smooth muscle contractile physiology. Our aim was to determine
      the effects of the denervation necessitated by jejunoileal autotransplantation on
      membrane potential and contractile activity. Six dogs underwent a model of
      jejunoileal autotransplantation that specifically avoids ischemia/reperfusion
      injury (by maintaining blood flow to the gut during the "transplantation"
      procedure). Strips of jejunal circular muscle were studied sequentially before
      and 2 and 8 weeks after denervation by recording mechanical and intracellular
      electrical activities in vitro. The amplitude of spontaneous contractions (X +/-
      SD) was increased (P < 0.05) at 2 compared to 0 weeks (126 +/- 19 vs 77 +/- 32
      g/g; P < 0.05) but markedly decreased at 8 weeks (7 +/- 2 g/g). Contraction
      frequency, resting membrane potential, and amplitude of slow waves were unchanged
      across these time points. Bethanechol (10(-7)-10(-4) M) and substance P (10(-8)
      10(-6) M) dose-dependently increased contractile activity at all time points, but
      the absolute change in amplitude was decreased at 8 weeks. The amplitude of
      inhibitory junction potentials (IJPs) and duration of inhibition of contractile
      activity in the presence of cholinergic and adrenergic blockade increased at 2
      and 8 weeks; off-contraction amplitude was decreased at 8 weeks (P < 0.05). These
      effects may occur via changes in neurotransmitter release, changes in regulation
      of membrane receptors, or alteration of characteristics of the membrane threshold
      potential.

PMID- 9009115
TI  - Left brachial approach for transcatheter arterial embolization therapy in
      patients with hepatocellular carcinoma.
AB  - We evaluated the efficacy of the lipiodol-transcatheter arterial embolization (L
      TAE) technique for hepatocellular carcinoma (HCC) performed using a left brachial
      approach. A total of 64 procedures were performed using the brachial route in 53
      patients with HCC between 1989 and 1996 using a 4-French catheter and these
      patients were retrospectively studied. The technical success rate was 95.3%. The
      overall complication rate was 31.3%: fever of over 38.0 degrees C lasting longer
      than three days (18.8%), transient neurologic complications (4.7%), and
      pancreatitis (1.6%). Complications such as lumbago, back pain, and dissection of
      the celiac artery or its branches, which frequently complicated femoral
      approaches, were avoided. These data indicate that L-TAE using the left brachial
      approach may be a safe and effective alternative to the transfemoral approach in
      patients with HCC.

PMID- 9009116
TI  - Transjugular intrahepatic portasystemic stent shunt in the treatment of variceal
      bleeding in hepatocellular cancer.

PMID- 9009117
TI  - A variant alkaline phosphatase-producing gastric carcinoma with super bone scan.

PMID- 9009118
TI  - Cigarette smoke increases gastric ulcer size in part by an angiotensin II
      mediated mechanism in rats.
AB  - To assess the mechanism of the effect of cigarette smoke on ulcer disease we
      employed a rat model in which cigarette smoke increases the size of acetic acid
      induced gastric ulcer and decreases the hyperemia at the ulcer margin. We
      postulate that cigarette smoke increases angiotensin II (a vasoconstrictor) in
      ulcer tissue. Since direct measurement of angiotensin II in small tissue samples
      is problematic, we compared the messenger ribonucleic acid (mRNA) for its
      precursors (angiotensinogen and renin) in ulcer and normal gastric tissue. We
      also evaluated the effect of enalapril, which blocks the conversion of
      angiotensin I to angiotensin II on ulcer size. In the ulcer tissue, cigarette
      smoke produced a significant increase in mRNA for angiotensinogen but not for
      renin. Enalapril decreased the size of the gastric ulcer in rats exposed to
      cigarette smoke. The data support the possibility that in ulcer tissue cigarette
      smoke stimulates an angiotensin II-mediated mechanism, which may in part be
      responsible for the impairment of ulcer margin hyperemia and aggravation of ulcer
      size.

PMID- 9009119
TI  - Effect of combined anticoagulation and low-dose aspirin treatment on upper
      gastrointestinal bleeding.
AB  - Multiple studies link the use of nonsteroidal antiinflammatory drugs (NSAIDs)
      with severe upper gastrointestinal bleeding (UGIB); the incidence of such
      bleeding is 2-4%. One common regimen to assure patency after intracoronary stent
      placement requires an anticoagulant (warfarin) combined with aspirin as an
      antiplatelet agent. However, a 13-fold increase in the risk of UGIB occurs with
      long-term use of oral anticoagulants and NSAIDs. We retrospectively assessed the
      rate of UGIB in 138 patients who had received coronary stents (group I, receiving
      heparin followed by warfarin in combination with aspirin) and 109 angioplasty
      patients without stents (group II, receiving aspirin alone) between 1990 and
      1994. UGIB was identified by hematemesis or melena, which led to gastrointestinal
      consultation. Patients were analyzed for multiple risk factors. UGIB occurred in
      28 of 138 group I patients (20%; 95% CI 13.3-26.7%) and 0 of 109 group II
      patients (P < 0.0001). Esophagogastroduodenoscopy (EGD) findings on the 28
      patients with UGIB included 13 patients with esophagitis or gastritis, 7 patients
      with gastric or duodenal ulcers, and 8 patients with no identifiable source of
      bleeding. UGIB occurred within a mean of 2.5 days of initiation of combination
      therapy. Of patients with UGIB, 10 required blood transfusion (mean number of
      units = 5.3). Previous history of peptic ulcer disease, smoking, and use of
      antiulcer medication did not significantly differ between the two groups. The
      concurrent use of anticoagulant and aspirin in patients with coronary stents
      creates a significant potential for UGIB and should be used only with extreme
      caution.

PMID- 9009120
TI  - Possible mechanism of increase in gastric mucosal PGE2 and PGI2 generation
      induced by ecabet sodium, a novel gastroprotective agent.
AB  - The gastroprotective agent ecabet sodium (ecabet, 12-sulfodehydroabietic acid
      monosodium salt) increases the formation of prostaglandin (PG) E2 and I2 by
      gastric mucosa. In the present study, we examined the effect of ecabet on
      metabolism of arachidonic acid (AA) in rat gastric mucosal cells. Ecabet (0.1-10
      mM) concentration- and time-dependently potentiated the release of [14C]AA from
      gastric mucosal cells prelabeled with [14C]AA and simultaneously increased the
      production of PGE2 and PGI2. The ecabet-mediated increases in [14C]AA release and
      PGE2 production were both partly depressed by mepacrine (30 and 100microM) and
      Ca2+ chelation. Ecabet, however, showed no effect on gastric phospholipase A2
      (PLA2) activity and [Ca2+]i in the gastric mucosal cells. Ecabet and other
      dehydroabietic acid derivatives, 12-carboxydehydroabietic acid monosodium salt
      and mono[16-(12-sulfodehydroabietyl)]succinic acid monosodium salt, which
      potentiated the liberation of [14C]AA, increased the membrane fluidity of gastric
      mucosal cells assessed by using diphenylhexatrienepropionic acid (DPH-PA) as the
      probe, while 12-sulfamoyldehydroabietic acid showed no effect on either the AA
      liberation or the membrane fluidity. Ecabet (0.1-10 mM) increased the membrane
      fluidity concentration- and time-dependently in accordance with its facilitating
      effect on AA release. In conclusion, ecabet increases the synthesis of PGE2 and
      PGI2 by gastric mucosal cells through promoting the release of AA, which is
      partly dependent on PLA2 and Ca2+. The ecabet-induced increase in membrane
      fluidity may be involved in part in the liberation of AA from the gastric mucosal
      cells.

PMID- 9009121
TI  - Histochemical analysis of hyperplastic stomach of TGF-alpha transgenic mice.
AB  - Hypertrophic gastric mucosa in transgenic mice overexpressing transforming growth
      factor (TGF)-alpha showed mucosal cellular hyperplasia with dysplasia,
      suppression of gastric acid secretion, and chief and parietal cell depletion. In
      order to clarify the effects of TGF-alpha on the gastric mucosa, we analyzed the
      stomach of TGF-alpha transgenic mice by mucin histochemical staining and
      immunohistochemical analysis of TGF-alpha. In transgenic mice, especially those
      older than 3 months, the fundic gland was notably atrophic but the total mucosa
      was thickened. The mucous neck cells were hypersecretory and associated with
      abnormal sulfation. Mucosal hyperplasia was caused by proliferation of surface
      epithelial cells, associated with formation of intracytoplasmic lumina. The
      hyperplastic foveolar cells revealed production of a high amount of sialomucin.
      In addition, the involved stomach regionally revealed collagenous fibrosis in the
      submucosal layer. The wide distribution of TGF-alpha in the hyperplastic foveolar
      cells was in sharp contrast to negative expression in the foveolar cells in the
      control mice. These findings demonstrated the various regulatory functions of TGF
      alpha in mucin production, fibrogenesis, and neck cell proliferation in the
      stomach.

PMID- 9009123
TI  - Helicobacter pylori infection has no role in the pathogenesis of reflux
      esophagitis.
AB  - In a prospective study of consecutive patients with reflux esophagitis and/or
      hiatal hernia and Barrett's esophagus, the prevalence of Helicobacter pylori was
      assessed. Antral biopsy specimens were studied and a serum sample for detection
      of IgG antibodies against Helicobacter pylori was taken. As a reference group
      patients presenting with a normal esophagus, stomach, and duodenum were taken.
      Reflux esophagitis was diagnosed in 118 patients, hiatal hernia without
      esophageal inflammation in 109, and Barrett's esophagus in 13. Helicobacter
      pylori was present in 74 (30%) of these patients and in 204 (51%) of the
      reference group. Prevalence of Helicobacter pylori was significantly lower in all
      groups compared with the reference group (P < 0.001). There was no difference
      when patients with esophagitis, Barrett's esophagus, or hiatal hernia were
      compared. Patients with esophagitis and Helicobacter pylori in their antrum are
      significantly older than esophagitis patients without concomitant Helicobacter
      infection, 61.5 (SD, 17) versus 53 (SD, 17) years (P < 0.001). It is concluded
      that the prevalence of Helicobacter pylori infection in patients with
      gastroesophageal reflux disease is significantly lower than in the reference
      group, irrespective of the severity of esophagitis. Helicobacter pylori infection
      has no role in the pathogenesis of reflux esophagitis.

PMID- 9009122
TI  - Gastric PCO2 tonometry is independent of carbonic anhydrase inhibition.
AB  - Tonometric measurement of an elevated intragastric Pco2 and a decreased
      calculated gastric intramucosal pH can be used to detect gastric mucosal
      ischemia, provided that intraluminal production of CO2 through acid buffering by
      bicarbonate is avoided by adequate acid secretion suppression. If the diffusion
      rate is known, steady state Pco2 can be calculated when measurement intervals are
      used that are shorter than needed for complete equilibration. The CO2 diffusion
      might be influenced by the choice of acid-suppressive drugs, since some of them
      inhibit gastric carbonic anhydrase (CA) and CA facilitates diffusion of
      CO2/bicarbonate over the gastrointestinal mucosa. We therefore performed gastric
      Pco2 tonometry, using acid-suppressive regimens with and without CA inhibition.
      The diffusion rate of CO2 in a gastric tonometer was studied in healthy
      volunteers, following intravenously administered ranitidine (group I, N = 8) or
      ranitidine plus pirenzepine (group II, N = 12), a muscarinic antagonist with CA
      inhibiting capacities. Measurement intervals were 10, 20, 30 and 60 min. Neither
      the diffusion rate of CO2 (k = 0.13 +/- 0.02/min in group I and 0.11 +/- 0.02/min
      in group II), nor the steady-state Pco2 (38 +/- 3 mm Hg in group I and 40 +/- 4
      mm Hg in group II), nor the gastric-blood differences in Pco2 and pH differed
      between groups. These results indicate that diffusion of CO2 into the tonometer
      balloon is independent of CA and thus of the type of gastric acid secretion
      inhibition.

PMID- 9009124
TI  - Esophageal and lower esophageal sphincter response to balloon distention in
      patients with achalasia.
AB  - Achalasia is characterized by absent or incomplete lower esophageal sphincter
      (LES) relaxation and aperistalsis in the smooth muscle esophageal body in
      response to swallowing. The esophageal and LES response to distention has not
      previously been studied. I aimed to characterize the responses to esophageal
      balloon distention in achalasia patients in comparison to controls. Sixteen
      consecutive achalasia patients and 11 healthy volunteers underwent standard
      esophageal manometry followed by graded midesophageal balloon distention during
      which LES (as measured by the Dent sleeve) and esophageal body pressures were
      monitored. Subject perception of distention was also recorded using a
      standardized scoring system. The LES relaxation response to esophageal balloon
      distention was markedly impaired in achalasia patients, irrespective of whether
      the patient had radiological evidence of a dilated or nondilated esophagus.
      However, phasic contractions proximal to the distending balloon were preserved.
      The esophageal body responses below the balloon were inconsistent in both groups,
      and not significantly different from one another. Pain-sensation scores were
      significantly lower in achalasia patients at the highest distending volumes, but
      this difference was attributable to the subgroup of patients with a dilated
      esophagus. Distention-induced LES relaxation is markedly impaired in achalasia
      patients in keeping with loss of intrinsic inhibitory innervation. Preservation
      of the proximal excitation suggests that extrinsic vagal reflexes are intact.

PMID- 9009125
TI  - Esophageal motor function in primary Sjogren's syndrome: correlation with
      dysphagia and xerostomia.
AB  - The incidence of dysphagia in patients with primary Sjogren's syndrome (pSS) has
      been underestimated and all too often ascribed to xerostomia, without considering
      the possible presence of esophageal motor abnormalities affecting other
      nonscleroderma connective tissue diseases. Esophageal and salivary functions were
      prospectively evaluated in 27 females who met the four criteria proposed by Fox
      for the diagnosis of pSS, using esophageal manometry after wet swallows and
      Saxon's test, respectively. Dysphagia was graded using a standard symptoms
      questionnaire and results were compared with those obtained in a group of 21
      healthy controls. Seven patients with pSS (26%) had no swallowing discomfort, 2
      (7.4%) had mild dysphagia, 7 (26%) had moderate dysphagia, and 11 (40.6%) had
      severe dysphagia. Saxon's test revealed an overall decrease in the salivary flow
      rate compared to controls, with no difference between patients with or without
      dysphagia. Esophageal manometry demonstrated the absence of any lower or upper
      esophageal sphincter function abnormalities in all patients. In the patients with
      pSS as a whole, manometric study of the esophageal body showed a motor pattern
      comparable with that of controls, with no difference between patients with and
      without dysphagia. Defective peristalsis, ie, the presence of simultaneous
      contractions in more than 30% of wet swallows was detected, however, in the
      distal tract of the esophagus of six patients (22.2%) and in the proximal tract
      of three (11.1%). All these patients had severe dysphagia and the modified
      Saxon's test revealed a salivary secretion comparable with that of patients with
      a normal peristalsis. Dysphagia is a very common complaint in patients with pSS
      and does not seem to correlate with xerostomia, which is a constant and typical
      finding of the disease. About one third of patients with pSS have an abnormal
      esophageal peristalsis that is responsible for severe dysphagia, whereas
      decreased salivary outflow exacerbates the swallowing discomfort. This has to be
      taken into account and justifies the routine use of esophageal manometry in
      patients with pSS. The cause of dysphagia in pSS patients without peristaltic
      disorders of the esophagus has to be investigated.

PMID- 9009126
TI  - Effect of fludrocortisone and spironolactone on sodium and potassium losses in
      secretory diarrhea.
AB  - The response of the colon to aldosterone is believed to be an important adaptive
      mechanism to excessive sodium losses in diarrhea. However, the degree to which
      mineralocorticoid activity actually influences fecal output of sodium in people
      with diarrhea is unknown. To gain insight into this question, 10 normal people
      were treated with placebo, fludrocortisone (an aldosterone agonist), and
      spironolactone (an aldosterone antagonist) during three experimental periods
      lasting nine days. On days 5-8, diarrhea was induced by ingestion of
      phenolphthalein. Diet was controlled. Fecal sodium was 40 meq/day on placebo and
      29 meq/day on fludrocortisone, consistent with mineralocorticoid stimulation of
      intestinal sodium absorption. However, contrary to our expectations,
      spironolactone therapy was also associated with a fall in fecal sodium output, to
      28 meq/day. To explain this paradoxical effect of spironolactone, we suggest that
      sodium depletion caused by spironolactone's natriuretic action on the kidney
      caused the release of an unknown stimulant of intestinal sodium absorption, whose
      action more than overcame the reduced colonic absorption resulting from
      inhibition of aldosterone activity by spironolactone. This interpretation implies
      that the intestinal adaptation to sodium depletion in diarrhea involves both
      aldosterone and an aldosterone independent factor, working in concert to reduce
      fecal sodium output.

PMID- 9009127
TI  - Relationship between site of disease and familial occurrence in Crohn's disease.
AB  - Concordance in the extent of disease among the family members of patients with
      Crohn's disease has not been widely investigated. Furthermore, the relationship
      between the site of the disease and familial occurrence has never been studied.
      Our aim was to evaluate the familial occurrence of Crohn's disease in the various
      sites. Nine hundred thirty-four patients with Crohn's disease, observed
      consecutively in two gastrointestinal departments, were investigated to determine
      first-degree familial incidence (in both Crohn's disease and ulcerative colitis).
      Whenever two or more members were attending the same clinic, only one was
      regarded as a propositus. The analysis, therefore, was carried out on 882
      patients. The exact site of the disease was determined in all patients either at
      diagnosis or during the follow-up by colonoscopy and by small bowel enema. The
      rate of concordance in the extent of disease and familial occurrence in the
      various sites was evaluated and the difference was calculated by chi-square test.
      Sixty-one propositi were identified among all the patients. Forty-nine had
      familial occurrence for the same disease (concordant patients), whereas 12 had at
      least one relative with ulcerative colitis (discordant patients). In 44 propositi
      with only one relative affected, the rates of concordance in the extent of the
      disease were 84, 68, 18, and 0% respectively, for the ileum, the ileum-right
      colon, the ileum-total colon, and the colon. The number of propositi in the
      various sites was as follows: 4 of 162 (2.4%) patients with the disease located
      in the colon, 1 of 9 (11%) with the jejunum site, 24 of 380 (6.3%) with the ileum
      site, 16 of 165 (9.7%) with the ileum and right colon site, and 16 of 164 (9.7%)
      with the ileum and total colon site. The chi-square values of propositi
      distribution among other sites and the colon was, respectively, as follows:
      jejunum, 2.2 (N.S.); ileum, 3.4 (P = 0.06); ileum and right colon, 7.4 (P =
      0.006); and ileum and total colon, 7.4 (P = 0.006). This study shows a pronounced
      concordance in the site of the disease for family members with Crohn's disease
      and suggests that familial occurrence in Crohn's disease is less frequent when
      the disease is located in the colon rather than elsewhere.

PMID- 9009128
TI  - Azoreductase and nitroreductase activity of bacteria in feces from patients with
      an ileal reservoir.
AB  - Azoreductase and nitroreductase activities of bacteria in feces of five patients
      with ileal reservoirs were evaluated, both at the onset of symptoms of pouchitis
      and following recovery after treatment with drugs. All stool samples tested had
      bacteria with azoreductase and nitroreductase activities. Azoreductase and
      nitroreductase activities were higher after recovery than during attacks of
      pouchitis. During reestablishment of the normal microflora in the ileal
      reservoirs after pouchitis, the anaerobic bacteria increased and the aerobic
      bacteria decreased.

PMID- 9009129
TI  - Determinants of lactose digestion in the miniature pig.
AB  - Although lactose is an important nutrient in the diet of the infant and child,
      the factors contributing to its digestion have not been clarified adequately. We
      sought to determine the degree to which lactase activity and small intestinal
      transit explain lactose digestion, the average error (SEE) in estimating lactose
      digestion using these parameters, and the effect of age. We compared lactose
      digestion from both a 7% lactose-containing formula and a solution by determining
      lactose in ileostomy output in pig littermates at 10 days, 4 weeks, and 10 weeks
      of age. The entire small intestinal mucosa was assayed for lactase specific
      activity (micromol x min-1 x g protein-1), total activity (micromol x min-1), and
      whole-villus lactase activity. Transit time (min), and transit rate (cm/min) were
      measured. Meal type did not affect lactose digestion. Lactose digestion was
      explained best by lactase specific activity (formula, R2 = 0.73, SEE = 1.1;
      solution, R2 = 0.69, SEE = 1.0; P < 0.001). The next best parameter was total
      transit rate (formula, R2 = 0.69, SEE = 2.0; solution, R2 = 0.46, SEE = 1.3). The
      relationship with lactase specific activity was age related and there appeared to
      be a critical value of lactase specific activity above which essentially all the
      lactose was digested.

PMID- 9009130
TI  - Ileoileal intussusception: classification based on its mechanical basis of
      occurrence.

PMID- 9009131
TI  - Chemolysis of gallbladder debris left over after contact litholysis with methyl
      tert-butyl ether.
AB  - Rapid and safe gallbladder clearance from residual, post-MTBE stone debris is
      believed to be absolutely necessary to reduce stone recurrence after contact
      litholysis. Because the clearing effect of prokinetic agents is considered an
      uncertain postdissolution trial, we investigated by in vitro experiments whether
      and to what extent debris from various cholesterol and "mixed stones" could be
      removed by direct (topical) chemolysis. Debris from radiolucent cholesterol
      stones could be dissolved very easily, using the aqueous solvent S-01, composed
      of EDTA-2Na (1-2%), lauryl sulfobetaine-12 (0.1 M), and 0.1 M sodium
      carbonate/boric acid buffer, pH 9,5. Its dissolution capacity (DC) was 8.06 +/-
      2.3 mg debris/ml and its dissolution efficacy (DE) was 16.2 +/- 4.6 mg
      debris/ml/hr. Debris from mixed, slightly to moderately calcified stones needed
      another treatment with S-05, composed of sodium citrate (0.25 M), lauryl
      sulfobetaine-12 (0.01 M), and citric acid. The initial pH was 5.2. The DC of S-05
      ranged from 1.61 +/- 1.1 (debris enriched with Ca-phosphate) to 3.94 +/- 1.3
      mg/ml (debris enriched with Ca-carbonate). Stones which did not respond
      immediately to MTBE because of a thin rim of inorganic or/and organic Ca salts
      could be made ready for MTBE litholysis by pretreatment with S-01 or S-05 or with
      a combination of both solvents. Debris containing large portions of biliary mucus
      could be dissolved most effectively by successive application of S-01 and S-06 (2
      M urea).

PMID- 9009133
TI  - Treatment of refractory ascites using transjugular intrahepatic portosystemic
      shunt (TIPS): a caution.
AB  - Ascites becomes refractory to medical treatment in nearly 10% of cirrhotic
      patients, who then require repeated large-volume paracentesis. In this
      prospective study we evaluated the use of transjugular intrahepatic portosystemic
      shunt (TIPS) in 30 patients with refractory ascites. TIPS was successful in all
      and resulted in a 54% reduction in portacaval gradient (from 22.8 +/- 0.8 to 10.4
      +/- 0.6 mm Hg). Ascites became easily controlled with diuretics in 26 patients
      following TIPS. Ascites recurrence associated with shunt stenosis was observed
      during follow-up in eight patients; revision could be undertaken in five of them
      and resulted in good control of ascites. In responders, a marked decrease in
      plasma aldosterone and renin activity, a reduction in serum creatinine, and a
      rise in urinary sodium excretion were observed. Creatinine and inulin clearances
      improved significantly; PAH clearance remained unchanged. However, new-onset or
      worsening hepatic encephalopathy was seen in 14 patients. Severe disabling
      chronic encephalopathy occurred in five patients; it could be reversed
      successfully by balloon occlusion of the shunt in three. The cumulative survival
      rate was 41 and 34% at 1 and 2 years, respectively. In summary, TIPS can control
      refractory ascites in a majority of patients but is associated with a high rate
      of chronic disabling HE. In addition, the survival rate is poor. Randomized
      trials are needed to evaluate the exact role of TIPS in the management of
      refractory ascites. It is unlikely to improve survival but can ameliorate quality
      of life in nontransplant candidates and be useful as a bridge to transplantation,
      in particular, to improve denutrition associated with longstanding tense ascites.

PMID- 9009132
TI  - Enhanced expression of cytokine-induced neutrophil chemoattractant (CINC) by
      bronchoalveolar macrophages in cerulein-induced pancreatitis rats.
AB  - The role of bronchoalveolar macrophages (BAMs) in the aggravation of cerulein
      induced pancreatitis was studied by measuring expression of cytokine-induced
      neutrophil chemoattractant (CINC) in vitro. Pancreatitis was induced by four
      intramuscular injections of cerulein (50 microg/kg at 1-hr intervals).
      Pancreatitis rats were injected intraperitoneally with 30 mg/kg
      lipopolysaccharide (LPS) 6 hr following the first cerulein injection as a septic
      challenge. Rats were divided into four groups: group I, nonpancreatitis without
      LPS; group II, pancreatitis without LPS; group III, nonpancreatitis with LPS; and
      group IV, pancreatitis with LPS. Hyperactivity of BAMs in response to LPS was
      assessed as a function of in vitro CINC production. CINC concentrations of the
      serum and bronchoalveolar lavage fluid in group IV were significantly higher than
      those in groups I, II, and III. BAMs in group II harvested 6 hr following the
      first cerulein injection had significantly greater CINC production than those in
      group I. Northern blot analysis revealed abundant CINC mRNA transcripts in BAMs
      from groups III and IV. Additionally, myeloperoxidase activity in the lung of
      group IV rats 8 and 12 hr following the first cerulein injection was
      significantly higher than that in group I, II, and III rats. Significant
      differences in static lung compliance in group IV were found compared with groups
      I, II, and III. These results indicate that BAMs from rats with cerulein-induced
      pancreatitis were primed and had enhanced release of CINC following LPS exposure.
      Enhanced expression of CINC may modulate the pathogenesis of pancreatitis
      associated lung injury complicated with sepsis.

PMID- 9009134
TI  - Liver metabolic zonation and hepatic microcirculation in carbon tetrachloride
      induced experimental cirrhosis.
AB  - The exact cause of the hepatic failure in liver cirrhosis is currently unclear,
      and two main theories have been proposed: the first is based on the altered
      hepatocyte function (sick hepatocyte hypothesis); the second on the abnormal
      hepatic architecture (intact hepatocyte hypothesis). Moreover, the
      microcirculation, a fundamental component in liver structure, shows dramatic
      changes in cirrhosis that would heavily influence the development of the disease.
      In order to determine the importance of the microvascular alterations on liver
      morphofunctional features in experimentally induced cirrhosis, their
      relationships with structural, ultrastructural, and histoenzymological hepatocyte
      modifications were investigated. Experimental cirrhosis was induced with
      controlled intragastric CCl4 administration. Scanning electron microscopy of the
      vascular corrosion cast technique, associated with light microscopy, transmission
      electron microscopy, and histoenzymology techniques were employed. The results
      demonstrated a characteristic micronodular cirrhosis in all the livers studied;
      the microcirculation displayed the presence of newly formed perinodular plexus.
      Inside the nodule, areas with two or more hepatocyte-thick laminae were present.
      Moreover, a rearrangement of the hepatocyte quantitative ultrastructure without
      real pathological changes and a loss of normal metabolic lobular zonation were
      noted in the liver parenchyma. These findings support the concept that the
      progressive modifications of the microcirculation during experimental CC14
      cirrhosis modify not only the normal blood flow direction, but also the normal
      hepatic metabolic gradient with a loss of the normal hepatocytic zonation.

PMID- 9009136
TI  - Morbidity of chronic hepatitis C as seen in a tertiary care medical center.
AB  - We studied the morbidity of chronic hepatitis C in patients referred to a
      tertiary care medical facility. The medical records of 500 consecutive cases of
      chronic hepatitis C were examined for the following: (1) source and time of
      exposure, (2) signs and symptoms of liver disease, (3) degree of alcohol intake,
      (4) liver biopsy findings, (5) extrahepatic disease manifestations, and (6)
      coexisting illnesses that could have an impact on morbidity. Morbidity and
      histologic findings were evaluated in relation to the duration of hepatitis C.
      The onset of infection could be determined in 376 patients (75%). A close
      relationship between the length of infection and disease features was not
      observed. Fatigue was common at all stages of infection. Whereas cirrhosis
      occurred more frequently in patients with disease of long duration, 15-24% of
      patients had signs of advanced liver disease (ascites, encephalopathy,
      thrombocytopenia) within six years of exposure. Overt extrahepatic manifestations
      of chronic hepatitis C occurred infrequently, and depression was reported in 24%
      of untreated patients. In conclusion, in patients referred to a tertiary care
      setting, chronic hepatitis C is often associated with significant morbidity.

PMID- 9009137
TI  - Cholestatic jaundice induced by ciprofloxacin.

PMID- 9009135
TI  - Effect of obesity on pharmacokinetics and biologic effect of interferon-alpha in
      hepatitis C.
AB  - To examine potential adverse effects of obesity in reducing the response to
      interferon-alpha (IFN-alpha) in chronic hepatitis C (HCV), IFN-alpha and HCV RNA
      levels in serum and the 2',5'-oligoadenylate synthetase (2-5 OAS) levels in
      peripheral blood mononuclear cells (PBMC) were compared between six obese and
      five nonobese patients before and after a single, 10 mIU dose of IFN-alpha2b.
      There were no differences in the mean histologic activity index between the two
      groups. The maximal IFN concentration and the area under the serum IFN
      concentration-time curve were higher in nonobese patients. These two parameters
      were inversely correlated with body weight and body surface area. No differences
      were found in the mean reduction in HCV RNA levels between the two groups
      following IFN-alpha. The maximal 2-5 OAS level after treatment divided by the
      pretreatment 2-5 OAS level (2-5 OAS response ratio) was greater in the nonobese
      patients, suggesting stronger biologic response upon exposure to exogenous IFN
      alpha in nonobese patients.

PMID- 9009138
TI  - Lactoferrin as a suppressor of cell migration of gastrointestinal cell lines.
AB  - The effects of lactoferrin (Lf), an iron-binding glycoprotein, on cell migration
      were investigated. Lf inhibited the cell migration of three gastrointestinal cell
      lines (Caco-2 cells, AGS cells, and IEC-18 cells) in vitro. Both iron-saturated
      (holo) and iron-depleted (apo) Lf showed this inhibitory effect. Chelation of
      iron in the culture medium by desferrioxamine did not affect the activity of
      either form of Lf. A pepsin hydrolysate of Lf exhibited effectiveness similar to
      that of intact Lf. These results demonstrate a novel activity of Lf and suggest a
      potential role for this molecule in gastrointestinal wound healing, which is
      independent of its iron-binding capacity.

PMID- 9009139
TI  - Intimal hyperplasia following vascular injury is not inhibited by an antisense
      thrombin receptor oligodeoxynucleotide.
AB  - Thrombin is a multifunctional serine protease with central functions in
      hemostasis, but demonstration of its role in the initiation and maintenance of
      cell proliferation which occurs following vascular injury is still lacking. To
      determine the role played by thrombin and its receptor in neointimal accumulation
      of smooth muscle cells in a rabbit carotid artery model, we have used an 18 mer
      antisense phosphorothioate oligonucleotide (ODN) directed against the translation
      initiation region of the human thrombin receptor gene. The antisense ODN
      inhibited in a dose-dependent manner thrombin- or thrombin receptor activating
      peptide-induced human aortic smooth muscle cell proliferation. The growth
      inhibitory effect of thrombin receptor antisense ODN was preventable by an excess
      of sense oligomer and specific for thrombin. The suppression of growth was
      accompanied by a marked decrease of the level of thrombin receptor expression as
      evidenced by [125I]-thrombin binding to smooth muscle cells. Under the same
      experimental conditions, the corresponding sense ODN was inactive. The effect of
      the antisense ODN on intimal smooth muscle hyperplasia in rabbit carotid arteries
      subjected to endothelial injury was then investigated. The topical application of
      the antisense (500 microg/artery) but not the sense ODN dissolved in F127
      pluronic gel around the injured artery resulted, 2 weeks after the application,
      in a dramatic reduction of the expression of the thrombin receptor mRNA and
      protein levels as determined by in situ hybridization and immunohistochemistry.
      However, intimal smooth muscle cell accumulation as estimated by an intimal to
      medial cross-sectional area ratio was reduced only by 2.7% (vs. 10.3% for the
      sense ODN), whereas r-hirudin (200 microg/kg/day, s.c.), a potent direct thrombin
      inhibitor significantly reduced the formation of neointima in denuded carotid
      arteries (35.4% inhibition, P = 0.03).

PMID- 9009140
TI  - Endoplasmic reticulum stress-inducible protein GRP94 is associated with an Mg2+
      dependent serine kinase activity modulated by Ca2+ and GRP78/BiP.
AB  - The 94-kDa glucose-regulated protein (GRP94) is a glycoprotein in the endoplasmic
      reticulum (ER). It has been characterized as a Ca2+-binding protein and a
      molecular chaperone. In this report we show that highly purified GRP94 exhibits
      an active Mg2+-dependent serine kinase activity (termed 94-kinase). The 94-kinase
      can be recovered from ER membrane fractions and is able to phosphorylate both the
      constitutive and stress-induced forms of GRP94, correlating with their induction
      kinetics. The 94-kinase activity is distinct from casein kinase II. In contrast
      to the heat-stable, Ca2+-dependent autophosphorylation activity recently reported
      for GRP94, the labile 94-kinase activity is inhibited by Ca2+. We determined that
      the phosphopeptide map of in vitro phosphorylated GRP94 by the 94-kinase
      resembles that of the in vivo phosphorylated GRP94. Further, the 94-kinase
      activity can be specifically stimulated by GRP78, a coregulated protein in the ER
      known to interact with GRP94.

PMID- 9009141
TI  - Tissue-specific differences in heat shock protein hsc70 and hsp70 in the control
      and hyperthermic rabbit.
AB  - The ability to resolve protein members of the hsp70 multigene family by two
      dimensional Western blotting permitted the characterization of antibodies which
      were specific in discriminating constitutively expressed hsc70 isoforms from
      stress-inducible hsp70 isoforms. This antibody characterization demonstrated that
      basal levels of hsp70 isoforms were present in the cerebellum of the control
      rabbit and that these were elevated following hyperthermia, whereas levels of
      hsc70 were similar in control and hyperthermic tissue. Multiple isoforms of hsp70
      were detected but tissue-specific differences were not apparent in various organs
      of the rabbit. However, species differences were observed as fewer hsp70 isoforms
      were noted in rat and mouse. In the control rabbit, higher levels of hsc70
      protein were present in neural tissues compared to non-neural tissues. Following
      physiologically relevant hyperthermia, induction of hsp70 was greatest in non
      neural tissues such as liver, heart, muscle, spleen, and kidney compared to
      regions of the nervous system. These studies suggest that the amount of
      preexisting constitutive hsc70 protein may influence the level of induction of
      hsp70 in the stress response. Given this observation, caution is required in the
      employment of hsp70 induction as an index of cellular stress since endogenous
      levels of hsc70, and perhaps hsp70, may modulate the level of induction.

PMID- 9009142
TI  - Control of fibronectin receptor expression by fibronectin: antisense fibronectin
      RNA downmodulates the induction of fibronectin receptor by transforming growth
      factor beta1.
AB  - The results of our previous studies of mouse embryo fibroblasts showed that
      fibronectin expression and fibronectin receptor expression are tightly
      coregulated and that fibronectin modulates expression of its receptor in response
      to treatment with the differentiation-inducing agent N,N,-dimethylformamide
      (Varani and Chakrabarty, 1990, J. Cell. Physiol., 143:445-454; Huang et al.,
      1994, J. Cell. Physiol., 161:470-482). We also found that transforming growth
      factor beta1 (TGFbeta1) induces a more differentiated phenotype in the epithelium
      derived human colon carcinoma cell line Moser and upregulates the expression of
      both fibronectin and its receptor (Huang and Chakrabarty, 1994, Int. J. Cancer,
      57:742-746). By expressing antisense fibronectin RNA in Moser cells, we have
      downregulated fibronectin mRNA expression and thus blocked the ability of
      TGFbeta1 to induce fibronectin expression (Huang and Chakrabarty, 1994, J. Biol.
      Chem., 269:28764-28768). In this study, we examined the effect of antisense
      fibronectin RNA expression on the induction of fibronectin receptor by TGFbeta1
      and tested the hypothesis that the induction of fibronectin expression by
      TGFbeta1 is required for the induction of fibronectin receptor expression.
      Blocking fibronectin induction by TGFbeta1 attenuated the ability of TGFbeta1 to
      upregulate the expression of cell-surface fibronectin receptors, alpha5beta1
      integrin expression, and adhesion to extracellular matrix fibronectin. We
      therefore conclude that induction of fibronectin expression is required for
      optimal upregulation of fibronectin receptor expression by TGFbeta1.

PMID- 9009143
TI  - Transforming growth factor beta1 inhibits collagenase 3 expression by
      transcriptional and post-transcriptional mechanisms in osteoblast cultures.
AB  - Transforming growth factor (TGF) beta1 is an autocrine regulator of bone cell
      function. We demonstrated that TGF beta1 enhances bone collagen synthesis, but
      its effects on collagen degradation are not well characterized. We tested the
      effects of TGF beta1 on rat collagenase 3 expression in cultures of osteoblast
      enriched cells from fetal rat calvariae (Ob cells). Treatment with TGF beta1 at
      0.4 nM decreased steady state collagenase mRNA levels after 2 to 24 h. This dose
      dependent effect was observed at TGF beta1 concentrations of 4 pM to 1.2 nM, and
      was accompanied by decreased levels of immunoreactive procollagenase. The protein
      synthesis inhibitor cycloheximide increased collagenase transcripts, but did not
      prevent the effect of TGF beta1 on collagenase mRNA levels. TGF beta1 accelerated
      the decay of collagenase mRNA in transcriptionally arrested Ob cells. In
      addition, TGF beta1 decreased the levels of collagenase heterogeneous nuclear RNA
      and the rate of collagenase gene transcription in Ob cells. TGF beta1 enhanced
      the expression of tissue inhibitors of metalloproteinases (TIMP) 1 and 3 and
      caused a modest decrease of TIMP 2 mRNA levels. In conclusion, TGF beta1
      decreases interstitial collagenase transcripts and protease levels in Ob cells by
      transcriptional and post-transcriptional mechanisms, and this effect may
      contribute to its actions on bone matrix.

PMID- 9009144
TI  - Activation of protein kinase A is a pivotal step involved in both BMP-2- and
      cyclic AMP-induced chondrogenesis.
AB  - We studied the roles of protein kinase A (PKA) activation and cyclic AMP response
      element binding protein (CREB) phosphorylation in chondrogenesis using serum-free
      chicken limb bud micromass cultures as a model system. We showed the following
      points: 1) in micromass cultures, activation of PKA enhances chondrogenesis and
      increases the phosphorylation of CREB; 2) BMP-2, a chondrogenic stimulator,
      increases PKA activity and the level of phosphorylated CREB (P-CREB); 3) H8, a
      PKA inhibitor, inhibits chondrogenesis; 4) the chondrogenic activities of BMP-2
      and cAMP are suppressed by H8; and 5) long-term TPA treatment (a protein kinase C
      (PKC) modulator) inhibits chondrogenesis and decreases the levels of CREB and P
      CREB. These results suggest that activation of PKA is a physiological event
      during chondrogenesis that is involved in the chondrogenic effects of both BMP-2
      and cyclic AMP (cAMP)-dependent pathways.

PMID- 9009145
TI  - Membrane depolarization in NRK fibroblasts by bradykinin is mediated by a calcium
      dependent chloride conductance.
AB  - The effects of the phosphoinositide-mobilizing agonist bradykinin (BK) on
      membrane potential and intracellular calcium in monolayers of normal rat kidney
      (NRK) fibroblasts were investigated. BK induced a rapid transient depolarization
      in these cells, which was mimicked by other phosphoinositide-mobilizing factors
      such as prostaglandin F2alpha (PGF2alpha), lysophosphatidic acid (LPA), platelet
      derived growth factor (PDGF-BB), and serum. Depolarization by BK was independent
      of extracellular Ca2+ or Na+. It was shown using extracellular Cl- substitutions
      that the depolarization was caused by an increased Cl- conductance.
      Depolarization was inhibited by 5-nitro-2-3-phenylpropyl(amino)benzoic acid
      (NPPB), niflumic acid, and flufenamic acid, inhibitors of calcium-dependent
      chloride channels. The depolarization provoked by BK could be mimicked by raising
      intracellular calcium with ionomycin or thapsigargin and could be blocked with
      geneticin, a blocker of phospholipase C. When intracellular calcium was buffered
      by loading the cells with 1,2-bis(2-aminophenoxy)ethane-NNN'N'-tetra-acetic acid
      (BAPTA), depolarization was prevented. We conclude that in NRK fibroblasts
      extracellular stimuli that increase intracellular calcium, depolarize the cells
      via the activation of a calcium-dependent chloride conductance. In addition to an
      increase in intracellular calcium, depolarization may be an important effector
      pathway in response to extracellular stimuli in fibroblasts. It is hypothesized
      that, in electrically coupled cells such as NRK fibroblasts, intercellular
      transmission of these depolarizations may represent a mechanism to coordinate
      uniform multicellular responses to Ca2+-mobilizing agonists.

PMID- 9009146
TI  - Mechanical stimulation of osteopontin mRNA expression and synthesis in bone cell
      cultures.
AB  - We have shown earlier that mechanical stimulation by intermittent hydrostatic
      compression (IHC) promotes alkaline phosphatase and procollagen type I gene
      expression in calvarial bone cells. The bone matrix glycoprotein osteopontin
      (OPN) is considered to be important in bone matrix metabolism and cell-matrix
      interactions, but its role is unknown. Here we examined the effects of IHC (13
      kPa) on OPN mRNA expression and synthesis in primary calvarial cell cultures and
      the osteoblast-like cell line MC3T3-E1. OPN mRNA expression declined during
      control culture of primary calvarial cells, but not MC3T3-E1 cells. IHC
      upregulated OPN mRNA expression in late released osteoblastic cell cultures, but
      not in early released osteoprogenitor-like cells. Also, in both proliferating and
      differentiating MC3T3-E1 cells, OPN mRNA expression and synthesis were enhanced
      by IHC, differentiating cells being more responsive than proliferating cells.
      These results suggest a role for OPN in the reaction of bone cells to mechanical
      stimuli. The severe loss of OPN expression in primary bone cells cultured without
      mechanical stimulation suggests that disuse conditions down-regulate the
      differentiated osteoblastic phenotype.

PMID- 9009147
TI  - Extreme N terminus of E1A oncoprotein specifically associates with a new set of
      cellular proteins.
AB  - By interacting with key regulatory proteins such as the pRb family, cyclins,
      cyclin-dependent kinases and p300/CBP of host cells, adenoviral E1A interferes
      with various cellular processes to provide a suitable environment for the
      replication of viruses. E1A may promote DNA synthesis and cell cycle progression,
      immortalize rodent cells in culture and transform cultured cells in cooperation
      with E1B, Ras, or other oncoproteins. Both extreme N terminus and conserved
      region 1 of E1A are required for the immortalization and the transformation of
      rodent cells, transcriptional repression and specific induction of the expression
      of cellular genes such as the proliferating cell nuclear antigen (PCNA) and heat
      shock protein 70 (HSP70). Although the molecular mechanisms of these functions of
      E1A are not fully understood, it is believed that protein-protein interactions
      may play essential roles. In this communication, we report that a new set of
      cellular proteins with apparent molecular weight of 200, 90, 45, 30, and 28
      specifically associate with the extreme N terminus of E1A. Further analysis
      demonstrate that these associations do not depend on E1A's association with p300
      or pRB. Neither the 30 kDa nor the 28 kDa polypeptide is identical to Cdc2 or
      Cdk2. The region of E1A required for the protein interaction is also required for
      the recently identified N-terminal transactivation activity of E1A. Our
      observations suggest that in addition to p300/CBP, the new set of cellular
      proteins may be involved in the functional complexity of the N terminus of E1A,
      thus predicting a p300/CBP independent pathway.

PMID- 9009148
TI  - c-myc-Dependent hepatoma cell apoptosis results from oxidative stress and not a
      deficiency of growth factors.
AB  - Expression of c-myc regulates apoptotic cell death in the human hepatoma cell
      line HuH-7 during culture in serum-free medium (SFM) plus zinc. To understand the
      mechanism of this c-myc effect, the ability of various serum-contained factors to
      prevent apoptosis was determined. Apoptosis was not inhibited by growth factors
      and was even accelerated by supplementation with insulin-like growth factor I or
      insulin. Cell death was prevented by SFM supplementation with the amino acid
      glutamine but not serine or asparagine. Improved cell survival with glutamine was
      associated with increased levels of glutathione (GSH). In HuH-7 cells cultured in
      SFM plus zinc, c-myc expression led to decreased levels of GSH, and elevated
      intracellular levels of hydrogen peroxide (H2O2). Cell death induced by c-myc
      expression was inhibited by the addition of catalase or dimethyl sulfoxide, a
      hydroxyl radical scavenger, or by increased intracellular expression of catalase.
      In contrast to findings in fibroblasts, c-myc-dependent apoptosis during serum
      deprivation in HuH-7 hepatoma cells was unrelated to a loss of growth factors.
      Apoptosis resulted from H2O2-mediated oxidative stress with associated glutamine
      dependent intracellular GSH depletion.

PMID- 9009150
TI  - Antiproliferative effect of the C-terminal fragments of parathyroid hormone
      related protein, PTHrP-(107-111) and (107-139), on osteoblastic osteosarcoma
      cells.
AB  - The C-terminal region of parathyroid hormone-related protein (PTHrP) containing
      the sequence (107-111) appears to be a potent inhibitor of osteoclastic bone
      resorption. In the present study, we have investigated the effect of human
      (h)PTHrP (107-139) and hPTHrP (107-111)NH2 on the proliferation of osteoblastic
      rat osteosarcoma UMR 106 cells. We found that both C-terminal PTHrP peptides,
      like hPTHrP (1-141), were antimitogenic for these cells, between 1 pM and 10 nM.
      [Tyr34]hPTHrP (1-34)NH2 was as potent as these peptides but less effective as
      growth inhibitor in these cells. UMR 106 cells were found to produce and secrete
      immunoreactive PTHrP. Addition of anti-PTHrP neutralizing antibodies to C- and N
      terminal epitopes of PTHrP increased the growth of these cells. Our data suggest
      that the antiproliferative effect of these C-terminal PTHrP analogs may be
      independent of cyclic adenosine 3':5'-monophosphate (cAMP) and mediated by
      protein kinase C. These findings support an autocrine role of PTHrP in bone
      metabolism.

PMID- 9009151
TI  - Presence and persistence of serum anti-benzo[a]pyrene diolepoxide-DNA adduct
      antibodies in smokers: effects of smoking reduction and cessation.
AB  - Among biomarkers of tobacco smoke (TS)-induced genotoxic damage, benzo[a]pyrene
      diolepoxide-DNA adducts (BPDE-DNA) are extensively studied. Adducted DNA becomes
      antigenic and antibodies anti-BPDE-DNA (BPDE-DNA-Abs) may be found in serum of
      exposed subjects. Little is known about the persistence of BPDE-DNA, and no study
      has been performed to evaluate the persistence of BPDE-DNA-Abs after cessation of
      exposure. Fifty heavy smokers, enrolled in a smoking cessation program with
      nicotine patch substitution therapy, were evaluated for the presence of BPDE-DNA
      Abs before (w0) and 1, 3, 6 and 12 weeks (w1-12) after the start of the program.
      Nicotine or placebo patches were randomly assigned to the subjects. BPDE-DNA-Abs
      were determined in serum by non-competitive ELISA. After the start of the
      cessation program, 28 subjects quit smoking (group Q) and the other 22 reduced by
      about 75% the number of cigarettes smoked per day (group R). At the start of the
      program (w0) 8% of subjects were positive. At w1 the prevalence of positivity had
      increased both in subjects who quit smoking (Q: 21%) and in subjects who had
      reduced the number of cigarettes per day (R: 27%). Positivity remained stable up
      to w12 (21%) for group Q, whereas it increased to 41% in group R. Serum BPDE-DNA
      Abs can be detected in smokers, and their persistence for months after smoking
      cessation suggests their usefulness for relatively long-term surveys. The low
      percentage of positivity in actual heavy smokers and the increase in antibody
      positivity with smoking cessation or reduction must be taken into account when
      interpreting serum BPDE-DNA-Ab measurement in exposed individuals.

PMID- 9009149
TI  - Tyrosine kinase inhibition decreases Muc-1 expression in mouse epithelial cells.
AB  - Mouse uterine epithelial cells (UEC) express high levels of both messenger RNA
      (mRNA) and protein encoding the polymorphic mucin glycoprotein, Muc-1, under most
      conditions in vivo and in vitro. Although steroid hormones modulate Muc-1
      expression in vivo, it is not clear if these actions are mediated directly by
      steroid hormone receptors or indirectly by modulation of key intracellular signal
      transduction cascades. To address the latter issue, we examined the effects of a
      wide variety of modulators of signal transduction cascades on the expression of
      Muc-1 in primary cultures of polarized mouse UEC. Transient exposure of UEC to
      agents that inhibit tyrosine kinases by distinct mechanisms, i.e., tyrphostin,
      genistein, and staurosporine, consistently and significantly reduced Muc-1
      expression. In contrast, a variety of agents that modulate protein kinase A- or C
      dependent pathways had little or no effect on Muc-1. The effect of tyrphostin
      proved to be similar in magnitude at both the level of Muc-1 protein and mRNA
      expression. Transient transfection assays of mouse UEC and a murine mammary
      epithelial cell line, NMuMG, with mouse Muc-1 promoter-CAT reporter constructs
      demonstrated a similar (50-60%) degree of tyrphostin inhibition. These
      observations suggested an action at the level of Muc-1 gene expression. Levels of
      100,000 g soluble tyrosine kinase activity in mouse UEC freshly isolated from
      estrous stage (high-level Muc-1 expression) and day 4 of pregnancy (low-level Muc
      1 expression) correlated with Muc-1 expression. Furthermore, pretreatment of day
      4 pregnant mice with the anti-progestin, RU486, an agent previously shown to
      restore or maintain high levels of Muc-1 expression, also restored soluble
      tyrosine kinase activity to levels similar to that observed in estrous stage
      mice. Collectively, these results indicate that tyrosine kinase activity is
      required to maintain high level Muc-1 expression in mice.

PMID- 9009152
TI  - Breast cancer risk associated with gynecologic surgery and indications for such
      surgery.
AB  - Risk of breast cancer was assessed in relationship to gynecologic operations
      using data from a record-linkage study involving 15,844 women in the Uppsala
      Health Care Region of Sweden, who underwent surgery between 1965 and 1983. Data
      abstracted from medical records for the breast cancer cases and a random sample
      of the cohort allowed examination of risk associated with these operations in
      regard to menopausal status and indications for the operations. Among women who
      were pre-menopausal at the time of operation, a bilateral oophorectomy before the
      age of 50 years was associated with a 50% reduction in the risk of breast cancer
      compared with the background population, a reduction in risk evident within 10
      years of the operation. A bilateral oophorectomy after the age of 50 years in pre
      menopausal women or after a natural menopause was not associated with any
      reduction in risk. There were no reductions in risk associated with a unilateral
      oophorectomy or hysterectomy among women who were pre-menopausal at the time of
      operation. In fact, hysterectomy alone was associated with a slight increase in
      breast cancer risk when the operation was due to myomas, abnormal bleeding, and,
      possibly, severe forms of endometriosis but not to other reasons. Risk did not
      vary substantially by indications for oophorectomy, including benign ovarian
      neoplasms and functional ovarian cysts, though endometriosis was associated with
      a non-significant increase in breast cancer risk.

PMID- 9009153
TI  - Pregnancy and risk of non-Hodgkin's lymphoma: a prospective study.
AB  - The etiology of non-Hodgkin's lymphomas (NHL), including chronic lymphocytic
      leukemia (CLL), is likely to be related to immune function. In the light of the
      established immunologic effects of a pregnancy, we decided to examine the risk of
      NHL and CLL in relationship to full-term pregnancies. Within a nationwide cohort
      we identified 1,546 women with NHL and 198 women with CLL, all 15 years or older,
      born 1925-1972. Five age-matched controls were selected for each case patient.
      Conditional logistic regression was used to estimate the odds ratios after mutual
      adjustment for number of births and age at first birth. We found a weak, negative
      association between parity and risk of NHL (p for trend 0.11) and a transient, 10
      40% decrease in risk within 5-14 years after the last birth among women with
      various parity status. The risk of CLL decreased more markedly, and orderly with
      increasing parity, but the trend was not significant (p = 0.18). Small numbers of
      cases with CLL prevented more detailed analyses of temporal relationships. Age at
      first birth appeared unrelated to the risk of both NHL and CLL. We conclude that
      the immunologic alterations associated with a pregnancy have limited, if any,
      relevance to the etiology of NHL and CLL; changing reproductive pattern is an
      unlikely contributor to the marked increase in incidence of NHL seen in many
      populations.

PMID- 9009154
TI  - Attributable risks for breast cancer in Italy: education, family history and
      reproductive and hormonal factors.
AB  - The percent population attributable risk (AR) for breast cancer was estimated in
      relation to education, family history of the disease and some reproductive and
      hormonal factors, using data from a case-control study conducted between June
      1991 and February 1994 in 6 Italian centres on 2,569 histologically confirmed
      incident breast cancer cases and 2,588 controls, admitted to hospital for a wide
      range of acute, non-neoplastic, non-hormone-related diseases. On the basis of
      multivariate odds ratios, a high level of education accounted for 20% of cases,
      elevated age at first birth and nulliparity for 38% and a family history of
      breast cancer in first-degree relatives for 7%. Education and nulliparity and age
      at first birth together explained 47% of all breast cancer cases, and the
      combination of these 2 factors plus a family history of the disease explained 50%
      of cases. In pre-menopausal women a high level of education accounted for 31% of
      all breast cancer cases, older age at first birth for 44% and the combination of
      the 2 factors for 49%. In post-menopausal women the corresponding values were
      13%, 31% and 42%; further addition of risk associated with family history of the
      disease explained 52% of pre-menopausal cases. In post-menopausal women older age
      at menopause and the use of hormone replacement therapy accounted for 15% and 2%
      of breast cancer cases, respectively. The combination of risks associated with a
      high level of education, old age at first birth and nulliparity and older age at
      menopause accounted for 51% of cases; further inclusion of risk associated with
      use of hormone replacement therapy explained 52%, and the AR resulting from these
      4 risk factors combined plus a family history of breast cancer was 56%. Thus, a
      few selected and well-identified risk factors explain about one-half the breast
      cancer cases in this Italian population.

PMID- 9009155
TI  - Breast-cancer mortality in a non-randomized trial on mammographic screening in
      women over age 65.
AB  - Recent case-referent studies in the Nijmegen breast-screening programme have
      shown a reduction in breast-cancer mortality of approximately 50% due to
      screening of women aged 65 years and older. In this type of study, however, the
      results may be biased because of self-selection. The purpose of our present study
      was to compare the breast-cancer mortality rate in a population invited for
      screening with that of a reference population from an area without a screening
      programme. In 1977-1978, 6773 women aged 68-83 years were enrolled in the
      mammographic screening programme in Nijmegen, The Netherlands. The women were
      followed up until 31 December, 1990. The reference population consisted of women
      from the same birth cohort from Arnhem, a neighbouring city without mass
      screening, for whom the entry date was 1 January, 1978. The ratios of the
      Nijmegen and Arnhem breast-cancer mortality rates with 95% confidence intervals
      (CI) were calculated. In the study period, 173 patients were diagnosed with
      primary breast cancer in Nijmegen vs. 183 in Arnhem; 40 Nijmegen patients had
      died of breast cancer vs. 51 Arnhem patients. The cumulative mortality-rate ratio
      was 0.80 (95% CI = 0.53-1.22). In the periods 1978-1981, 1982-1985 and 1986-1990,
      the mortality rate ratios were 1.44 (95% CI = 0.67-3.10), 081 (95% CI = 0.37
      1.79) and 0.53 (95% CI = 0.27-1.04), respectively. After adjustment for the
      difference in incidence rate that existed between the Nijmegen and Arnhem
      populations, mammographic screening of women older than 65 can be expected to
      yield a 40% reduction in breast-cancer mortality after 10 years.

PMID- 9009156
TI  - Microglial cells induce cytotoxic effects toward colon carcinoma cells:
      measurement of tumor cytotoxicity with a gamma-glutamyl transpeptidase assay.
AB  - Activated macrophages have been shown to exert cytostatic and cytotoxic effects
      toward tumor cells via nitric oxide (NO) release. In the CNS, microglial cells
      are considered to be the main resident population of immune effector cells. In
      this study, cytotoxic activity of N11, an immortalized murine microglial cell
      line, toward rat progressive DHD/PROb and regressive DHD/REGb colon carcinoma
      cells was examined in parallel with NO production. Cytotoxicity was evaluated
      using a novel method, the gamma-glutamyl transpeptidase (gamma-GTP) assay, based
      on the fact that DHD tumor cells expressed high levels of gamma-GTP activity,
      while no gamma-GTP activity was found in cells of the monocyte/macrophage
      lineage. Results showed that activation of N11 cells by interferon-gamma plus
      either lipopolysaccharide or tumor necrosis factor-alpha induced high amounts of
      NO release and cytotoxic effects toward DHD/PROb as well as DHD/REGb cells. NO
      release by activated N11 cells was augmented by addition of tumor cell
      conditioned medium. Both NO release by N11 cells and cytotoxicity were blocked by
      addition of N(G)-monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase,
      suggesting that cytotoxicity was mediated by N11-derived NO. However, in the
      presence of L-NMA an increased production of interleukin-6 was also observed. In
      conclusion, in opposition to information obtained with brain-derived endothelial
      cells, brain-derived microglial cells did not differentiate between progressive
      and regressive clones of colon carcinoma cells. Our results point to a specific
      role for both endothelial and microglial cell types in the context of brain
      metastasis. Microglial cells can be cytotoxic for tumor cells, and this
      cytotoxicity is mediated by NO.

PMID- 9009157
TI  - Ornithine decarboxylase over-expression stimulates mitogen-activated protein
      kinase and anchorage-independent growth of human breast epithelial cells.
AB  - In these experiments we tested the hypothesis that constitutive activation of
      polyamine(PA) biosynthesis may contribute to mammary carcinogenesis.
      Spontaneously immortalized normal human MCF-10A breast epithelial cells were
      infected with the retroviral vector pLOSN containing a cDNA which codes for a
      truncated and more stable ornithine decarboxylase (ODC), the rate-limiting enzyme
      in PA synthesis. Upon chronic selective pressure with alpha-difluoromethyl
      ornithine (DFMO) (an irreversible inhibitor of ODC), infected MCF-10A cells
      exhibited an approximately 250-fold increase in ODC activity, which persisted
      despite discontinuation of DFMO. ODC-over-expressing MCF-10A cells showed a
      modest decrease in S-adenosylmethionine decarboxylase and an increase in
      spermidine/spermineN1-acetyltransferase. Analysis of cellular PA profile revealed
      a selective accumulation of putrescine without alterations in spermidine and
      spermine contents. Lesser degrees of increased ODC activity were obtained
      reproducibly by re-exposing the cells to incremental small doses of DFMO. We
      observed a bell-shaped dose-related positive effect of ODC activity on
      clonogenicity in soft agar of MCF-10A cells. Since anchorage-dependent growth was
      actually reduced, such positive influence on this feature of transformation was
      not a non-specific consequence of a growth advantage provided by ODC over
      expression. In addition, we observed a close parallelism between the dose
      dependent effects of ODC expression on clonogenicity and activity of the ERK-2
      kinase, a central element of the MAPK cascade. Our data demonstrate an
      interaction between PA and the MAPK signalling pathway and suggest that the
      latter may be involved in ODC-induced transformation of mammary epithelial cells.

PMID- 9009158
TI  - Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir
      therapy leads to systemic activity against spontaneous and induced metastasis in
      an orthotopic mouse model of prostate cancer.
AB  - It is critical to develop new therapies, such as gene therapy, which can impact
      on both local and metastatic prostate cancer progression. We have developed an
      orthotopic mouse model of metastatic prostate cancer using a cell line (RM-1)
      derived from the mouse prostate reconstitution (MPR) model system. This mouse
      model closely simulates the anatomical and biological milieu of the prostate and
      allows for realistic testing of experimental gene therapy protocols. Adenovirus
      (ADV)-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk)
      gene in conjunction with ganciclovir (GCV) in this model led to significant
      suppression of growth and of spontaneous metastasis at 14 days post-tumor
      inoculation. Longer-term studies produced a significant survival advantage and a
      continued suppression of metastatic activity for treatment animals despite
      regrowth of the primary tumor. Challenge by injection of tumor cells into the
      tail vein following excision of treated and control s.c. primary tumors resulted
      in 40% reduction in lung colonization in the treatment group, indicating the
      possible production of systemic anti-metastatic activity following a single in
      situ treatment with ADV/HSV-tk + GCV in this model system.

PMID- 9009159
TI  - 17beta-estradiol, diethylstilbestrol, tamoxifen, toremifene and ICI 164,384
      induce morphological transformation and aneuploidy in cultured Syrian hamster
      embryo cells.
AB  - To examine the ability of estrogens and anti-estrogens to induce cellular
      transformation and genetic effects, Syrian hamster embryo (SHE) cells were
      treated with estrogens, 17beta-estradiol (E2) or diethylstilbestrol (DES), or
      with anti-estrogens, tamoxifen (TAM), toremifene (TOR) or ICI 164,384. Treatment
      with each substance for 1-3 days suppressed cellular growth in a dose-dependent
      manner. Colony-forming efficiency (CFE) increased following treatment of cells
      with E2 or DES for 48 hr at 3 or 10 microM but decreased at 20 or 30 microM. In
      contrast, CFE was increased by treatment with TAM, TOR or ICI 164,348 over the
      concentration range examined (1-30 microM). Treatment with each chemical at 1-30
      microM for 48 hr caused morphological transformation of SHE cells in a dose
      related fashion. The highest frequency was exhibited in SHE cells treated with
      DES at 20 microM and was 2 times higher than that induced by treatment with
      benzo[alpha]pyrene (B[alpha]P) at 4 microM. Transformation frequencies induced by
      other substances (E2, TAM, TOR and ICI 164,348) did not exceed that induced by
      the B[alpha]P treatment. TOR showed a higher transforming ability over all
      concentrations examined when compared to the other anti-estrogens (TAM and ICI
      164,348). No significant increases in the frequencies of chromosomal aberrations
      were observed in SHE cells that were treated with any of the chemicals. However,
      treatment of SHE cells with each chemical induced a dose-dependent increase of
      aneuploid cells in the near diploid range. Our results indicate that the ability
      of the estrogens and anti-estrogens to induce numerical chromosomal abnormality
      may be involved in their cell transformation activity and potential
      carcinogenicity.

PMID- 9009160
TI  - All-trans, 13-cis and 9-cis retinoic acids induce a fully reversible growth
      inhibition in HNSCC cell lines: implications for in vivo retinoic acid use.
AB  - Retinoids are a group of vitamin A analogues that have shown promise as
      chemopreventive and therapeutic agents in many types of malignancy and have been
      entered in clinical trials with some successful results. To better understand the
      mechanism that mediates retinoid action and the anti-proliferative effects, we
      treated 7 human oral squamous-cell carcinoma (SCC) cell lines (FADU, HEp-2, CCL
      17, SCC-9, SCC-15, SCC-25 and HN-212) with 10(-6) M of all-trans retinoic acid
      (ATRA), 9-cis and 13-cis retinoic acid (RA) in continuous for different periods
      of time. We assessed the extent of growth inhibition, the stability of the anti
      proliferative effect and the mRNA expression levels (by RT-PCR) of RA receptors
      (RARs), retinoid X receptors alpha (RXR alpha) and cytosolic RA-binding proteins
      (CRBP I and CRABP II) in treated cells compared with controls. The data obtained
      showed that all 3 RAs were able to inhibit the cellular growth of the tested cell
      lines, although to a different extent. The cis compounds were able to inhibit the
      proliferation of all cell lines, whereas ATRA was ineffective in inhibiting the
      proliferation of the CCL-17 cell line, which was naturally resistant to ATRA
      concentrations in the range between 10(-5) and 10(-6) M. All inhibitory effects
      were completely reversible since all cell lines restored their normal growth
      proliferation within few days after drug removal. RT-PCR analysis of the receptor
      and cell binding protein status of control and treated cells showed a good
      correlation between growth inhibition and induction of, or increase in, the
      expression levels of RAR beta in RA-treated cells. No differences were observed
      in RAR alpha and RXR alpha mRNA expression levels between control and treated
      cells. CRBP I, CRABP II and RAR gamma mRNA levels increased in some treated cell
      lines but not in all.

PMID- 9009161
TI  - Platelets mediate tumor cell adhesion to the subendothelium under flow
      conditions: involvement of platelet GPIIb-IIIa and tumor cell alpha(v) integrins.
AB  - The aim of our study was to explore the role of platelets and their specific
      integrin receptors in mediating the interaction of 4 human tumor cell lines (3
      melanoma and 1 carcinoma) with the extracellular matrix (ECM) under static and
      arterial flow conditions. Under static conditions, all 4 cell lines adhered to
      the ECM. The adhesion capacity of all 4 cell lines was virtually abolished by
      application of flow during incubation with the ECM. Under static conditions,
      tumor cell adhesion was not affected by adding platelets to the cell suspension
      and was slightly reduced by pre-coating the ECM with platelets prior to the
      addition of tumor cells. In contrast, under flow conditions, platelets
      significantly increased tumor cell adhesion to the ECM, the enhancing effect
      being more pronounced when platelets were pre-incubated with the ECM prior to the
      addition of tumor cells than when incubated simultaneously with the cells.
      Platelet-mediated tumor cell adhesion under flow was markedly inhibited by
      blockade of the platelet GPIIb-IIIa or of the tumor cell alpha(v) integrins.
      Platelets of a Glanzmann thrombastenia (GT) patient were unable to support tumor
      cell adhesion to the ECM under flow. Our results suggest that the interaction of
      tumor cells with subendothelium-bound platelets under flow conditions is mediated
      by platelet GPIIb-IIIa and by tumor cell alpha(v) integrins independently of the
      nature of the beta subunit.

PMID- 9009162
TI  - Multiple Grb2-protein complexes in human cancer cells.
AB  - Grb2 is an SH2/SH3 domain-containing adaptor protein that links receptor tyrosine
      kinases to the ras signaling pathway. The Grb2-SH2 domain binds phosphotyrosine
      sequences on activated tyrosine kinases, and one target of the SH3 domains is the
      ras-nucleotide-exchange factor Sos1. We have examined Grb2-protein interactions
      in human cancer cells that over-express the receptor tyrosine kinase erbB2. Our
      results show that the 2 Grb2-SH3 domains complex with Sos1, dynamin and at least
      4 other proteins (p228, p140, p55, p28) in these cells. The 2 Grb2-SH3 domains
      bind these proteins differently, with the N-terminal SH3 domain interacting
      preferentially with p228, Sos1, p140 and dynamin. The C-terminal SH3 domain has
      higher affinity toward p28. The Grb2-SH3 domain interactions appear to be similar
      in erbB2 over-expressing breast, ovarian and lung cancer cells. Also, the major
      tyrosine-phosphorylated proteins that associate with Grb2 in erbB2 over
      expressing cancer cells appear to be erbB2 and Shc. The multiple Grb2-SH3 domain
      interactions in these cells may mediate novel cellular functions.

PMID- 9009163
TI  - Paclitaxel-induced apoptosis in MCF-7 breast-cancer cells.
AB  - A study of MCF-7 human breast cancer cells was undertaken to ascertain the degree
      of apoptosis induction by paclitaxel and if the induction of apoptosis could be
      enhanced by caffeine. Paclitaxel (0-20 ng/ml) caused concentration-dependent
      increases in morphologically identifiable apoptotic cells (up to 43% of cell
      population) and cells with DNA strand breaks (up to 38%), a commonly cited marker
      of apoptosis. Maximal DNA strand breakage occurred after 16 hr of exposure to
      paclitaxel and maximal apoptotic-appearing cells occurred after 24 hr. The
      remaining non-apoptotic paclitaxel-exposed cells were growth arrested in G2. A 4
      hr exposure to caffeine concentration-dependently (0-20 mM) increased apoptosis
      to 88% of the cell population. Our results show induction of apoptosis in breast
      cancer cells by paclitaxel, and enhancement of this process by caffeine.

PMID- 9009164
TI  - Effects of the tyrosine-kinase inhibitor geldanamycin on ligand-induced Her-2/neu
      activation, receptor expression and proliferation of Her-2-positive malignant
      cell lines.
AB  - Geldanamycin belongs to the family of benzoquinoid ansamycin tyrosine-kinase
      inhibitors. We have examined its effects on Her-2/neu kinase activity, protein
      expression level, and proliferation of Her-2+ malignant cells. In SK-BR-3 breast
      cancer cells, short-time treatment with geldanamycin completely abrogated gp30
      ligand-induced activation of Her-2 without a change of receptor-expression level.
      Longer treatment of intact cells with geldanamycin induced decreased steady-state
      Her-2 autophosphorylation activity, which correlated with reduction of Her-2
      protein expression and phosphotyrosine content of several proteins. The decrease
      was time- and dose-dependent, starting after 1 hr at 100 nM concentration and
      reaching completion by 24 hr. The reduction of the Her-2 protein level probably
      resulted from increased degradation, since the Her-2 mRNA level remained
      constant. Geldanamycin effects were not specific for Her-2, since the non
      receptor tyrosine-kinase fyn was inhibited equally. In contrast to these results,
      protein-kinase-C activity was not affected. In 3 other malignant cell lines
      expressing different amounts of Her-2 (SK-BR-3 > SK-OV-3 > OVCAR3 > MCF7),
      geldanamycin also effectively reduced Her-2-kinase activity proportionally to the
      decrease of protein expression. In contrast, in a [3H]-thymidine-uptake assay,
      cell growth was meaningfully inhibited by geldanamycin at nanomolar
      concentrations only in SK-BR-3 (IC50 2 nM) and MCF7 (IC50 20 nM), while OVCAR3
      was only moderately sensitive (IC50 2 microM) and SK-OV-3 was clearly resistant
      to geldanamycin. In direct comparison with herbimycin A, another benzoquinoid
      ansamycin that has been more thoroughly characterized, the biologic effects of
      geldanamycin were more pronounced.

PMID- 9009166
TI  - Circadian-system alterations during cancer processes: a review.
AB  - Murine and human data have indicated that tumors and tumor-bearing hosts may
      exhibit nearly normal or markedly altered circadian rhythms. Amplitude damping,
      phase shifts, and/or period (tau) change, including appearance of ultradian
      rhythms (with tau < 20 hr) usually become more prominent at late stages of cancer
      development. The extent of rhythm alterations also varies according to tumor
      type, growth rate and level of differentiation. While "group chronotherapy,"
      i.e., administration of the same chronomodulated schedule to cancer patients, has
      increased chemotherapy efficacy and/or tolerability, cancer patients' individual
      circadian rhythms now need to be explored on a large scale, in order to estimate
      the incidence of cancer-associated circadian-system alterations and to understand
      the underlying mechanisms. Correlations between such alterations and patient
      outcome must be established in order to specify the need for individualized
      chronomodulated delivery schedules and/or specific rhythm-oriented therapy,
      especially in patients with circadian-system disturbances.

PMID- 9009165
TI  - Human ovarian-carcinoma cell lines express IL-4 and IL-13 receptors: comparison
      between IL-4- and IL-13-induced signal transduction.
AB  - We have reported that human ovarian-carcinoma cell lines express high-affinity IL
      4 receptor. Since IL-4R has been hypothesized to share a chain with IL-13R, we
      investigated whether ovarian cancer cells express IL-13 receptor. In the present
      study, we report that the ovarian-carcinoma cell lines IGROV-1 and PA-1 express
      varying numbers of high-affinity IL-13 receptors. Furthermore, IL-13 inhibited
      the binding of IL-4 on both ovarian-carcinoma cell lines, while IL-4 did not
      inhibit IL-13 binding on IGROV-1 cell line. IL-13 and IL-4 induced the
      phosphorylation of JAK1, JAK2 and Tyk2 Janus kinases in PA-1 cells. In contrast,
      JAK3 tyrosine kinase was expressed in PA-1 cells, but IL-4 or IL-13 did not
      augment its phosphorylation. In IGROV-1 cells, Tyk2 was constitutively
      phosphorylated and this phosphorylation was augmented by IL-4 or IL-13. JAK1 and
      JAK2 but not JAK3 were expressed but only JAK2 was faintly phosphorylated in
      response to either IL-13 or IL-4 respectively. IRS (insulin-receptor substrate)-1
      and IRS-2 were also phosphorylated constitutively in both ovarian cancer cell
      lines examined, but only the phosphorylation of IRS-1 was augmented in response
      to IL-4 or IL-13. STAT6 was phosphorylated and activated in response to IL-4 and
      IL-13 in all cell lines examined. Our results demonstrate that ovarian cancer
      cell lines may express 2 types of IL-13R and the IL-13- or IL-4-induced signaling
      patterns may be slightly different in each type of receptor.

PMID- 9009167
TI  - Taxol induces tyrosine phosphorylation of Shc and its association with Grb2 in
      murine RAW 264.7 cells.
AB  - Taxol, a natural product with significant anti-tumor activity, stabilizes
      microtubules and arrests cells in the G2/M phase of the cell cycle. It has been
      reported that taxol has additional effects in cells, including an increase in
      tyrosine phosphorylation of proteins and activation of MAP kinase. We
      investigated a possible effect of taxol on tyrosine phosphorylation of Shc and on
      formation of the Shc/Grb-2 complex in the murine macrophage-like cell line RAW
      264.7. Shc, an SH2 domain containing adaptor protein, was immunoprecipitated from
      lysates of taxol-treated cells with anti-phosphotyrosine antibody and its
      identity determined by Western blotting with anti-Shc antibody. Non-denatured Shc
      containing protein complexes were immunoprecipitated with anti-Shc antibody, and
      analysis with an anti-Grb2 antibody revealed the presence of the 24-kDa Grb2
      protein. Taxol also activated Raf-1 kinase and ERK1/ERK2 MAP kinases in these
      cells. These results demonstrate that taxol affects tyrosine phosphorylation of
      Shc and this may result in the activation of the Raf-1/MAPK cascade.

PMID- 9009168
TI  - Republican senators promote a doubling of funds for research.

PMID- 9009169
TI  - Insurance levy could fund medical centres.

PMID- 9009170
TI  - Health scientists strike over cuts at Argentinian labs.

PMID- 9009171
TI  - Study discloses financial interests behind papers.

PMID- 9009172
TI  - First German BSE case worries consumers.

PMID- 9009173
TI  - UCSF settles lawsuit over research costs.

PMID- 9009174
TI  - Pig heart transplant surgeon held in jail.

PMID- 9009175
TI  - Japan's demography poses questions for old and young alike.

PMID- 9009176
TI  - Canada and France fall out over the risks of asbestos.

PMID- 9009177
TI  - Peer reviewers could do much better.

PMID- 9009178
TI  - Unitary construction.

PMID- 9009179
TI  - Not 0 but O.

PMID- 9009180
TI  - Ways to surmount the language barrier.

PMID- 9009181
TI  - NO prizes.

PMID- 9009182
TI  - New wrinkles in cytokinesis.

PMID- 9009183
TI  - Structure of a molecular hole-punch.

PMID- 9009184
TI  - Help from within for damaged axons.

PMID- 9009185
TI  - Calcium channels. Integration hot-spot gets hotter.

PMID- 9009186
TI  - Carl Sagan (1934-96)

PMID- 9009187
TI  - Blindsight in normal subjects?

PMID- 9009188
TI  - A new Late Eocene anthropoid primate from Thailand.
AB  - The fossil record of anthropoid primates from the Middle Eocene of South Asia is
      so far restricted to two genera (Pondaungia cotteri Pilgrim, 1937 and
      Amphipithecus mogaungensis Colbert, 1937 from the Eocene Pondaung deposits of
      Burma) whose anthropoid status and phylogenetic position have long been under
      debate because they represent the oldest highly derived fossil primates of
      anthropoid grade. Moreover, several new African taxa, some of which are even
      older, have been recently included in the suborder Anthropoidea, suggesting an
      African origin for this group. Conversely, new fossil primates recently
      discovered in China (Eosimias) have been related to the most primitive
      representatives of Anthropoidea, alternatively suggesting an Asian origin and a
      probable Asian radiation centre. We report here the discovery of a new anthropoid
      from the Thai Late Eocene locality of Krabi, which displays several additional
      anthropoid characters with regard to those of the Eocene Burmese genera. This
      species, which is about the size of the Fayum Aegyptopithecus, can be related to
      the Burmese forms, and it further provides strong additional evidence for a
      southeast Asian evolutionary centre for anthropoids.

PMID- 9009189
TI  - Language-specific phoneme representations revealed by electric and magnetic brain
      responses.
AB  - There is considerable debate about whether the early processing of sounds depends
      on whether they form part of speech. Proponents of such speech specificity
      postulate the existence of language-dependent memory traces, which are activated
      in the processing of speech but not when equally complex, acoustic non-speech
      stimuli are processed. Here we report the existence of these traces in the human
      brain. We presented to Finnish subjects the Finnish phoneme prototype /e/ as the
      frequent stimulus, and other Finnish phoneme prototypes or a non-prototype (the
      Estonian prototype /o/) as the infrequent stimulus. We found that the brain's
      automatic change-detection response, reflected electrically as the mismatch
      negativity (MMN), was enhanced when the infrequent, deviant stimulus was a
      prototype (the Finnish /o/) relative to when it was a non-prototype (the Estonian
      /o/). These phonemic traces, revealed by MMN, are language-specific, as /o/
      caused enhancement of MMN in Estonians. Whole-head magnetic recordings located
      the source of this native-language, phoneme-related response enhancement, and
      thus the language-specific memory traces, in the auditory cortex of the left
      hemisphere.

PMID- 9009190
TI  - Bcl-2 promotes regeneration of severed axons in mammalian CNS.
AB  - Most neurons of the mammalian central nervous system (CNS) lose the ability to
      regenerate severed axons in vivo after a certain point in development. At least
      part of this loss in regenerative potential is intrinsic to neurons. Although
      embryonic retinal ganglion cells (RGCs) can grow axons into tectum of any age,
      most RGCs from older animals fail to extend axons into CNS tissue derived from
      donors of any age, including the embryonic tectum. Here we report that the proto
      oncogene bcl-2 plays a key role in this developmental change by promoting the
      growth and regeneration of retinal axons. This effect does not seem to be an
      indirect consequence of its well-known anti-apoptotic activity. Another anti
      apoptotic drug, ZVAD, supported neuronal survival but did not promote axon
      regeneration in culture. This finding could lead to new strategies for the
      treatment of injuries to the CNS.

PMID- 9009191
TI  - Competitive binding of alpha-actinin and calmodulin to the NMDA receptor.
AB  - The mechanisms by which neurotransmitter receptors are immobilized at
      postsynaptic sites in neurons are largely unknown. The activity of NMDA (N-methyl
      D-aspartate) receptors is mechanosensitive and dependent on the integrity of
      actin, suggesting a functionally important interaction between NMDA receptors and
      the postsynaptic cytoskeleton. alpha-Actinin-2, a member of the
      spectrin/dystrophin family of actin-binding proteins, is identified here as a
      brain postsynaptic density protein that colocalizes in dendritic spines with NMDA
      receptors and the putative NMDA receptor-clustering molecule PSD-95. alpha
      Actinin-2 binds by its central rod domain to the cytoplasmic tail of both NR1 and
      NR2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA
      receptors and PSD-95 from rat brain. Intriguingly, NR1-alpha-actinin binding is
      directly antagonized by Ca2+/calmodulin. Thus alpha-actinin may play a role in
      both the localization of NMDA receptors and their modulation by Ca2+.

PMID- 9009192
TI  - Crosstalk between G proteins and protein kinase C mediated by the calcium channel
      alpha1 subunit.
AB  - The modulation of voltage-dependent Ca2+ channels at presynaptic nerve terminals
      is an important factor in the control of neurotransmitter release and synaptic
      efficacy. Some terminals contain multiple Ca2(+)-channel subtypes (N and P/Q),
      which are differentially regulated by G-protein activation and by protein kinase
      C (PKC)-dependent phosphorylation. Regulation of channel activity by crosstalk
      between second messenger pathways has been reported although the molecular
      mechanisms underlying crosstalk have not been described. Here we show that
      crosstalk occurs at the level of the presynaptic Ca2(+)-channel complex. The
      alpha1 subunit domain I-II linker, which connects the first and second
      transmembrane domains, contributes to the PKC-dependent upregulation of channel
      activity, while G-protein-dependent inhibition occurs through binding of
      Gbetagamma to two sites in the I-II linker. Crosstalk results from the PKC
      dependent phosphorylation of one of the Gbetagamma binding sites which
      antagonizes Gbetagamma-induced inhibition. The results provide a mechanism for
      the highly regulated and dynamic control of neurotransmitter release that depends
      on the integration of multiple presynaptic signals.

PMID- 9009193
TI  - Direct binding of G-protein betagamma complex to voltage-dependent calcium
      channels.
AB  - Voltage-dependent Ca2+ channels play a central role in controlling
      neurotransmitter release at the synapse. They can be inhibited by certain G
      protein-coupled receptors, acting by a pathway intrinsic to the membrane. Here we
      show that this inhibition results from a direct interaction between the G-protein
      betagamma complex and the pore-forming alpha1 subunits of several types of these
      channels. The interaction is mediated by the cytoplasmic linker connecting the
      first and second transmembrane repeats. Within this linker, binding occurs both
      in the alpha1 interaction domain (AID), which also mediates the interaction
      between the alpha1 and beta subunits of the channel, and in a second downstream
      sequence. Further analysis of the binding site showed that several amino-terminal
      residues in the AID are critical for Gbetagamma binding, defining a site distinct
      from the carboxy-terminal residues shown to be essential for binding the beta
      subunit of the Ca2+ channel. Mutation of an arginine residue within the N
      terminal motif abolished betagamma binding and rendered the channel refractory to
      G-protein modulation when expressed in Xenopus oocytes, showing that the
      interaction is indeed responsible for G-protein-dependent modulation of Ca2+
      channel activity.

PMID- 9009194
TI  - Traction forces of cytokinesis measured with optically modified elastic
      substrata.
AB  - Animal cells dividing in culture undergo a dramatic sequence of morphological
      changes, characterized by cytoskeletal disassembly as cells round up,
      redistribution of actin, myosins and other cytoplasmic and surface molecules into
      the cleavage furrow, and respreading, before daughter cells finally separate at
      the mid-body. Knowledge of forces governing these movements is critical to
      understanding their mechanisms, including whether formation of the cleavage
      furrow results from increased force generation at the equator or relaxation at
      the poles, and whether traction force subsequently mediates cytofission of the
      intercellular bridge. We have quantitatively mapped traction forces in dividing
      cells, by extending the silicone-rubber substratum method to detect forces of
      nanonewtons to micronewtons. We used a new silicone polymer to fabricate
      substrata whose compliance can be adjusted precisely by ultraviolet irradiation.
      We show that traction force appears locally at the furrow in the absence of
      relaxation at the poles during cleavage. Force also rises as connected daughter
      cells respread and attempt to separate, suggesting that tension contributes to
      the severing of the intercellular bridge when cytokinesis is completed.

PMID- 9009195
TI  - HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell
      cycle checkpoint.
AB  - Hox11 is an orphan homeobox gene that controls the genesis of the spleen. HOX11
      is also oncogenic, having been isolated from a chromosomal breakpoint in human T
      cell leukaemia. Transgenic mice that redirected HOX11 to the thymus demonstrated
      cell-cycle aberration and progression to malignancy. We observed that the protein
      HOX11 interacted with protein serine-threonine phosphatase 2A catalytic subunit
      (PP2AC), as well as protein phosphatase 1 (PP1C) in mammalian cells. Inhibition
      of PP2A can regulate the cell cycle and control the activation of maturation
      promoting factor in Xenopus oocytes. Microinjection of HOX11 into Xenopus oocytes
      arrested at the G2 phase of the cell cycle promoted progression to the M phase.
      G2 arrest can be induced by gamma-irradiation, but is eliminated by expression of
      HOX11 within a T-cell line. Thus HOX11 is a cellular oncogene that targets PP2A
      and PP1, both of which are targets for oncogenic viruses and chemical tumour
      promoters. This interaction suggests a mechanism by which a homeobox can alter
      the cell cycle.

PMID- 9009196
TI  - The structure of the GTPase-activating domain from p50rhoGAP.
AB  - Members of the Rho family of small G proteins transduce signals from plasma
      membrane receptors and control cell adhesion, motility and shape by actin
      cytoskeleton formation. They also activate other kinase cascades. Like all other
      GTPases, Rho proteins act as molecular switches, with an active GTP-bound form
      and an inactive GDP-bound form. The active conformation is promoted by guanine
      nucleotide exchange factors, and the inactive state by GTPase-activating proteins
      (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. Rho
      specific GAP domains are found in a wide variety of large, multi-functional
      proteins. Here we report the crystal structure of an active 242-residue C
      terminal fragment of human p50rhoGAP. The structure is an unusual arrangement of
      nine alpha-helices, the core of which includes a four-helix bundle. Residues
      conserved across the rhoGAP family are largely confined to one face of this
      bundle, which may be an interaction site for target G proteins. In particular, we
      propose that Arg 85 and Asn 194 are involved in binding G proteins and enhancing
      GTPase activity.

PMID- 9009197
TI  - Crystal structure of colicin Ia.
AB  - The ion-channel forming colicins A, B, E1, Ia, Ib and N all kill bacterial cells
      selectively by co-opting bacterial active-transport pathways and forming voltage
      gated ion conducting channels across the plasma membrane of the target bacterium.
      The crystal structure of colicin Ia reveals a molecule 210 A long with three
      distinct functional domains arranged along a backbone of two extraordinarily long
      alpha-helices. A central domain at the bend of the hairpin-like structure
      mediates specific recognition and binding to an outer-membrane receptor. A second
      domain mediates translocation across the outer membrane via the TonB transport
      pathway; the TonB-box recognition element of colicin Ia is on one side of three
      80 A-long helices arranged as a helical sheet. A third domain is made up of 10
      alpha-helices which form a voltage-activated and voltage-gated ion conducting
      channel across the plasma membrane of the target cell. The two 160 A-long alpha
      helices that link the receptor-binding domain to the other domains enable the
      colicin Ia molecule to span the periplasmic space and contact both the outer and
      plasma membranes simultaneously during function.

PMID- 9009198
TI  - Ends Xist, but where are the beginnings?

PMID- 9009199
TI  - Xist-deficient mice are defective in dosage compensation but not spermatogenesis.
AB  - The X-linked Xist gene encodes a large untranslated RNA that has been implicated
      in mammalian dosage compensation and in spermatogenesis. To investigate the
      function of the Xist gene product, we have generated male and female mice that
      carry a deletion in the structural gene but maintain a functional Xist promoter.
      Mutant males were healthy and fertile. Females that inherited the mutation from
      their mothers were also normal and had the wild-type paternal X chromosome
      inactive in every cell. In contrast to maternal transmission, females that carry
      the mutation on the paternal X chromosome were severely growth-retarded and died
      early in embryogenesis. The wild-type maternal X chromosome was inactive in every
      cell of the growth-retarded embryo proper, whereas both X chromosomes were
      expressed in the mutant female trophoblast where X inactivation is imprinted.
      However, an XO mouse with a paternally inherited Xist mutation was healthy and
      appeared normal. The imprinted lethal phenotype of the mutant females is
      therefore due to the inability of extraembryonic tissue with two active X
      chromosomes to sustain the embryo. Our results indicate that the Xist RNA is
      required for female dosage compensation but plays no role in spermatogenesis.

PMID- 9009200
TI  - Null mutation of the prolactin receptor gene produces multiple reproductive
      defects in the mouse.
AB  - Mice carrying a germ-line null mutation of the prolactin receptor gene have been
      produced by gene targeting in embryonic stem cells. Heterozygous females showed
      almost complete failure of lactation attributable to greatly reduced mammary
      gland development after their first, but not subsequent, pregnancies. Homozygous
      females were sterile owing to a complete failure of embryonic implantation.
      Moreover, they presented multiple reproductive abnormalities, including irregular
      cycles, reduced fertilization rates, defective preimplantation embryonic
      development, and lack of pseudopregnancy. Half of the homozygous males were
      infertile or showed reduced fertility. This work establishes the prolactin
      receptor as a key regulator of mammalian reproduction, and provides the first
      total ablation model to further study the role of the prolactin receptor and its
      ligands.

PMID- 9009201
TI  - Stat5a is mandatory for adult mammary gland development and lactogenesis.
AB  - Prolactin (PRL) induces mammary gland development (defined as mammopoiesis) and
      lactogenesis. Binding of PRL to its receptor leads to the phosphorylation and
      activation of STAT (signal transducers and activators of transcription) proteins,
      which in turn promote the expression of specific genes. The activity pattern of
      two STAT proteins, Stat5a and Stat5b, in mammary tissue during pregnancy suggests
      an active role for these transcription factors in epithelial cell differentiation
      and milk protein gene expression. To investigate the function of Stat5a in
      mammopoiesis and lactogenesis we disrupted this gene in mice by gene targeting.
      Stat5a-deficient mice developed normally and were indistinguishable from
      hemizygous and wild-type littermates in size, weight, and fertility. However,
      mammary lobuloalveolar outgrowth during pregnancy was curtailed, and females
      failed to lactate after parturition because of a failure of terminal
      differentiation. Although Stat5b has a 96% similarity with Stat5a and a
      superimposable expression pattern during mammary gland development it failed to
      counterbalance for the absence of Stat5a. These results document that Stat5a is
      the principal and an obligate mediator of mammopoietic and lactogenic signaling.

PMID- 9009202
TI  - Immunological defects in mice with a targeted disruption in Bcl-3.
AB  - The proto-oncogene bcl-3 is a member of the IkappaB family. The Bcl-3 protein is
      known to interact specifically with the p50 and p52 subunits of NFkappaB.
      However, the function of this interaction is not well understood. To determine
      the in vivo role of Bcl-3, mice were generated that lack the bcl-3 gene, Bcl 3(-/
      ). Here we report that Bcl 3(-/-) mice appear developmentally normal, but exhibit
      severe defects in humoral immune responses and protection from in vivo pathogenic
      challenges. Relative to wild-type mice, Bcl 3(-/-) mice are unable to clear L.
      monocytogenes and are more susceptible to infection with S. pneumoniae. This
      phenotype is similar to that observed in the p50(-/-) mice and the cross between
      the Bcl-3(-/-) and p50(-/-) mice generates animals with an enhanced phenotype. In
      accordance with the observed defects in their immune response, the Bcl 3(-/-)
      mice have normal immunoglobulin levels before and after immunization, but fail to
      produce antigen-specific antibodies. Additionally, spleens from Bcl-3(-/-) mice
      are abnormal and void of germinal centers. In contrast, the p50(-/-) mice have
      normal germinal centers. We propose that in in vivo, Bcl-3 can function
      independently of p50.

PMID- 9009204
TI  - The product of proliferation disrupter is concentrated at centromeres and
      required for mitotic chromosome condensation and cell proliferation in
      Drosophila.
AB  - Homozygosity for a null mutation in the proliferation disrupter (prod) gene of
      Drosophila causes decreased mitotic index, defects of anaphase chromatid
      separation, and imperfect chromosome condensation in larval neuroblasts and other
      proliferating cell populations. The defective condensation is especially obvious
      near the centromeres. Mutant larvae show slow growth and massive cell death in
      proliferating cell populations, followed by late larval lethality. Loss of prod
      function in mitotic clones leads to the arrest of oogenesis in the ovary and
      defective cuticle formation in imaginal disc derivatives. The prod gene encodes a
      novel 301-amino-acid protein that is ubiquitously expressed and highly
      concentrated at the centric heterochromatin of the second and third mitotic
      chromosomes, as well as at > 400 euchromatic loci on polytene chromosomes. We
      propose that Prod is a nonhistone protein essential for chromosome condensation
      and that the chromosomal and developmental defects are caused by incomplete
      centromere condensation in prod mutants.

PMID- 9009203
TI  - Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and
      flexibility.
AB  - Pit-1, a member of the POU domain family of transcription factors, characterized
      by a bipartite DNA-binding domain, serves critical developmental functions based
      on binding to diverse DNA elements in its target genes. Here we report a high
      resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a
      homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular
      faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is
      accomplished by different spacing and orientation of the POU-specific domain.
      Contrary to previous predictions, the dimerization interface involves the
      carboxyl terminus of the DNA recognition helix of the homeodomain, which in an
      extended conformation interacts with specific residues at the amino terminus of
      helix alpha1 and in the loop between helices alpha3 and alpha4 of the POU
      specific domain of the symmetry related monomer. These features suggest the
      molecular basis of disease-causing mutations in Pit-1 and provide potential basis
      for the flexible allostery between protein domains and DNA sites in the
      activation of target genes.

PMID- 9009205
TI  - Identification of Bmi1-interacting proteins as constituents of a multimeric
      mammalian polycomb complex.
AB  - The Bmi1 gene has been identified as a mouse Polycomb group (Pc-G) gene
      implicated in the regulation of Hox gene expression. Here we describe the
      characterization of a Bmi binding protein Mph1, which shares similarity to
      Drosophila polyhomeotic. Coimmunoprecipitation experiments indicate that Bmi1 and
      Mph1, as well as the Mel18 and M33 proteins described previously, are
      constituents of a multimeric protein complex in mouse embryos and human cells. A
      central domain of Bmi1 interacts with the carboxyl terminus of Mph1, whereas a
      conserved alpha-helical domain in the Mph1 protein is required for its
      homodimerization. Transgenic mice overexpressing various mutant Bmi1 proteins
      demonstrate that the central domain of Bmil is required for the induction of
      anterior transformations of the axial skeleton. Bmi1, M33, and Mph1 show an
      overlapping speckled distribution in interphase nuclei. These data provide
      molecular evidence for the existence of a mammalian Polycomb complex.

PMID- 9009206
TI  - An unusual form of transcriptional silencing in yeast ribosomal DNA.
AB  - Generalized transcriptional repression of large chromosomal regions in
      Saccharomyces cerevisiae occurs at the silent mating loci and at telomeres and is
      mediated by the silent information regulator (SIR) genes. We have identified a
      novel form of transcriptional silencing in S. cerevisiae in the ribosomal DNA
      (rDNA) tandem array. Ty1 retrotransposons marked with a weakened URA3 gene (Ty1
      mURA3) efficiently integrated into rDNA. The mURA3 marker in rDNA was
      transcriptionally silenced in a SIR2-dependent manner. MET15 and LEU2 were also
      partially silenced, indicating that rDNA silencing may be quite general. Deletion
      of SIR4 enhanced mURA3 and MET15 silencing, but deletion of SIR1 or SIR3 did not
      affect silencing, indicating that the mechanism of silencing differs from that at
      telomeres and silent mating loci. Deletion of SIR2 resulted in increased psoralen
      cross-linking of the rDNA in vivo, suggesting that a specific chromatin structure
      in rDNA down-regulates polymerase II promoters.

PMID- 9009207
TI  - Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast.
AB  - We demonstrate that in Saccharomyces cerevisiae, the tandem array of ribosomal
      RNA genes (RDN1) is a target for integration of the Ty1 retrotransposon that
      results in silencing of Ty1 transcription and transposition. Ty1 elements
      transpose into random rDNA repeat units and are mitotically stable. In addition,
      we have found that mutation of several putative modifiers of RDN1 chromatin
      structure abolishes silencing of Ty1 elements in the rDNA array. Disruption of
      SIR2, which elevates recombination in RDN1, or TOP1, which increases psoralen
      accessibility in rDNA, or HTA1-HTB1, which reduces histone H2A-H2B levels and
      causes localized chromatin perturbations, abolishes transcriptional silencing of
      Ty1 elements in RDN1. Furthermore, deletion of the gene for the ubiquitin
      conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not
      only Ty1 transcription but also mitotic recombination in RDN1. On the basis of
      these results, we propose that a specialized chromatin structure exists in RDN1
      that silences transcription of the Ty1 retrotransposon.

PMID- 9009208
TI  - A complex structure in the mRNA of Tf1 is recognized and cleaved to generate the
      primer of reverse transcription.
AB  - All retroviruses and LTR-containing retrotransposons are thought to require
      specific tRNA molecules to serve as primers of reverse transcription. An
      exception is the LTR-containing retrotransposon Tf1, isolated from
      Schizosaccharomyces pombe. Instead of requiring a tRNA, the reverse transcriptase
      of Tf1 uses the first 11 bases of the Tf1 transcript as the primer for reverse
      transcription. The primer is generated by a cleavage that occurs between bases 11
      and 12 of the Tf1 mRNA. Sequence analysis of the 5' untranslated region of the
      Tf1 mRNA resulted in the identification of a region with the potential to form an
      RNA structure of 89 bases that included the primer binding site and the first 11
      bases of the Tf1 mRNA. Systematic mutagenesis of this region revealed 34 single
      point mutants in the structure that resulted in reduced transposition activity.
      The defects in transposition correlated with reduced level of Tf1 reverse
      transcripts as determined by DNA blot analysis. Evidence that the RNA structure
      did form in vivo included the result that strains with second site mutations that
      restored complementarity resulted in increased levels of reverse transcripts and
      Tf1 transposition. The majority of the mutants defective for reverse
      transcription were unable to cleave the Tf1 mRNA between bases 11 and 12. These
      data indicate that formation of an extensive RNA structure was required for the
      cleavage reaction that generated the primer for Tf1 reverse transcription.

PMID- 9009209
TI  - Coordination sphere and structure of the Mn cluster of the oxygen-evolving
      complex in photosynthetic organisms.
AB  - The great similarity between the binding of Fe(II) and the high-affinity Mn
      binding site in the Mn-depleted PSII membranes (Semin et al. (1996) FEBS Lett.
      375, 223-226) suggests that the coordination sphere of Mn in PSII is also
      suitable for iron. A comparison is performed between the primary amino acid
      sequences of D1 and D2 and diiron-oxo enzymes with the function of oxygen
      activation. All conservative motifs (EXXH) and residues binding and stabilizing
      the diiron cluster in diiron-oxo enzymes have been found in the C-terminal
      domains of D1 and D2 polypeptides. On the basis of these sequence similarities we
      suggest a structural model for the manganese cluster in the oxygen-evolving
      complex.

PMID- 9009210
TI  - Substrate properties of C'-methyl UTP derivatives in T7 RNA polymerase reactions.
      Evidence for N-type NTP conformation.
AB  - The number of synthetic UTP analogues containing methyl groups in different
      positions of the ribose moiety were tested as substrates for T7 RNA polymerase
      (T7 RNAP). Two of these compounds (containing substituents in the 5' position)
      were shown to be weak substrates of T7 RNAP. 3'Me-UTP was neither substrate nor
      inhibitor of T7 RNAP while 2'Me-UTP was shown to terminate RNA chain synthesis.
      Conformational analysis of the analogues and parent nucleotide using the force
      field method indicates that the allowed conformation of UTP during its
      incorporation into the growing RNA chain by T7 RNAP is limited to the chi angle
      range of 192-256 degrees of N-type conformation.

PMID- 9009211
TI  - Rapid sequence-independent cellular response to oligodeoxynucleotides.
AB  - The presence of receptors for oligodeoxynucleotides (OdN) on the surface of L929
      cells has previously been described. To study the possible coupling of the
      receptor to cellular signal transducing systems, the effect of phosphodiester OdN
      of different sequences on cellular phospholipase C and protein kinase C (PKC)
      activities in L929 fibroblasts was studied. Treatment of cells with OdN induced
      an increase in 32P labeling of phosphatidic acid which was accompanied by a
      gradual decrease in diacylglycerol. These effects seem to be independent of the
      OdN sequence. PKC activity in membranes isolated from OdN-treated cells was found
      to be lower than that in membranes of control cells. SDS-PAGE of the 32P-labeled
      cellular proteins revealed that OdN treatment caused a decrease in
      phosphorylation of the 26 and 73 kDa cellular proteins in the cells.

PMID- 9009212
TI  - Biosynthesis of isoprenoids in higher plant chloroplasts proceeds via a
      mevalonate-independent pathway.
AB  - Isopentenyl diphosphate (IPP) is the biological C5 precursor of isoprenoids. By
      labeling experiments using [1-(13)C]glucose, higher plants were shown to possess
      two distinct biosynthetic routes for IPP biosynthesis: while the cytoplasmic
      sterols were formed via the acetate/mevalonate pathway, the chloroplast-bound
      isoprenoids (beta-carotene, lutein, prenyl chains of chlorophylls and
      plastoquinone-9) were synthesized via a novel IPP biosynthesis pathway
      (glyceraldehyde phosphate/pyruvate pathway) which was first found in eubacteria
      and a green alga. The dichotomy in isoprenoid biosynthesis in higher plants
      allows a reasonable interpretation of previous odd and inconclusive results
      concerning the biosynthesis of chloroplast isoprenoids, which so far had mainly
      been interpreted in the frame of models using compartmentation of the mevalonate
      pathway.

PMID- 9009213
TI  - Secretion and binding of HMG1 protein to the external surface of the membrane are
      required for murine erythroleukemia cell differentiation.
AB  - We show here that murine erythroleukemia (MEL) cells, following induction with
      hexamethylene bisacetamide, accumulate high mobility group (HMG)1 protein onto
      the external surface of the cell in a membrane-associated form detectable by
      immunostaining with a specific anti-HMG1 protein antibody. This association is
      maximal at a time corresponding to cell commitment. At longer times,
      immunostainable cells are progressively reduced and become almost completely
      undetectable along with the appearance of hemoglobin molecules. Binding to MEL
      cells does not affect the native molecular structure of HMG1 protein. The type of
      functional correlation between HMG1 protein and MEL cell differentiation is
      suggested by the observation that if an anti-HMG1 protein antibody is added at
      the same time of the inducer almost complete inhibition of cell differentiation
      is observed, whereas if the antibody is added within the time period in which
      cells undergo through irreversible commitment, inhibition progressively
      disappears. A correlation between MEL cell commitment and the biological effect
      of HMG1 protein can thus be consistently suggested.

PMID- 9009214
TI  - Protein tyrosine phosphatase activity modulation by endothelin-1 in rabbit
      platelets.
AB  - Protein tyrosine phosphorylation, modulated by the rate of both protein tyrosine
      kinase and protein tyrosine phosphatase activities, is critical for cellular
      signal transduction cascades. We report that endothelin-1 stimulation of rabbit
      platelets resulted in a dose- and time-dependent tyrosine phosphorylation of four
      groups of proteins in the molecular mass ranges of 50, 60, 70-100 and 100-200 kDa
      and that one of these corresponds to focal adhesion kinase. This effect is also
      related to the approximately 60% decrease in protein tyrosine phosphatase
      activity. Moreover, this inhibited activity was less sensitive to orthovanadate.
      In the presence of forskolin that increases the cAMP level a dose-dependent
      inhibition of the endothelin-stimulated tyrosine phosphorylation of different
      protein substrates and a correlation with an increase in the protein tyrosine
      phosphatase activity (11.6-fold compared to control) have been found. Further
      studies by immunoblotting of immunoprecipitated soluble fraction with anti
      protein tyrosine phosphatase-1C from endothelin-stimulated platelets have
      demonstrated that the tyrosine phosphorylation of platelet protein tyrosine
      phosphatase-1C is correlated with the decrease in its phosphatase activity. As a
      consequence, modulation and regulation by endothelin-1 in rabbit platelets can be
      proposed through a cAMP-dependent pathway and a tyrosine phosphorylation process
      that may affect some relevant proteins such as focal adhesion kinase.

PMID- 9009215
TI  - Evidence for the involvement of cGMP and protein kinase G in nitric oxide-induced
      apoptosis in the pancreatic B-cell line, HIT-T15.
AB  - Intracellular production of nitric oxide (NO) is thought to mediate the
      pancreatic B-cell-directed cytotoxicity of cytokines in insulin-dependent
      diabetes mellitus, and recent evidence has indicated that this may involve
      induction of apoptosis. A primary effect of NO is to activate soluble guanylyl
      cyclase leading to increased cGMP levels and this effect has been demonstrated in
      pancreatic B-cells, although no intracellular function has been defined for islet
      cGMP. Here we demonstrate that the NO donor, GSNO, induces apoptosis in the
      pancreatic B-cell line HIT-T15 in a dose- and time-dependent manner. This
      response was significantly attenuated by micromolar concentrations of a specific
      inhibitor of soluble guanylyl cyclase, ODQ, and both 8-bromo cGMP (100 microM)
      and dibutyryl cGMP (300 microM) were able to fully relieve this inhibition. In
      addition, incubation of HIT-T15 cells with each cGMP analogue directly promoted
      cell death in the absence of ODQ. KT5823, a potent and highly selective inhibitor
      of cGMP-dependent protein kinase (PKG), abolished the induction of cell death in
      HIT cells in response to either GSNO or cGMP analogues. This effect was dose
      dependent over the concentration range of 10-250 nM. Overall, these data provide
      evidence that the activation of apoptosis in HIT-T15 cells by NO donors is
      secondary to a rise in cGMP and suggest that the pathway controlling cell death
      involves activation of PKG.

PMID- 9009216
TI  - Identification of the region that plays an important role in determining
      antibacterial activity of bovine seminalplasmin.
AB  - Seminalplasmin (SPLN) is a 47-residue protein isolated from bovine seminal plasma
      having potent antimicrobial activity against a broad spectrum of microorganisms.
      SPLN, also known as caltrin, acts as a calcium transport regulator in bovine
      sperms. Analysis of the sequence of SPLN reveals a 27-residue stretch with the
      sequence SLSRYAKLANRLANPKLLETFLSKWIG more hydrophobic than the rest of the
      protein. It is demonstrated that a synthetic peptide corresponding to this 27
      residue segment has antimicrobial activity comparable to that of SPLN. It does
      not exhibit hemolytic activity at concentrations where antibacterial activity is
      observed. Since P27 can be conveniently obtained in large amounts by chemical
      synthesis, it could serve not only as a starting compound to obtain peptides with
      improved antibacterial activity but also to understand the role of SPLN in
      reproductive physiology.

PMID- 9009217
TI  - Residue Glu-91 of Chlamydomonas reinhardtii ferredoxin is essential for electron
      transfer to ferredoxin-thioredoxin reductase.
AB  - The [2Fe-2S] soluble ferredoxin from Chlamydomonas reinhardtii was mutated by
      site directed mutagenesis, using PCR and the expression plasmid pET-Fd as a
      template. The recombinant mutated proteins were purified to homogeneity and
      tested in the activation of NADP-malate dehydrogenase, a light dependent reaction
      in which ferredoxin thioredoxin reductase (FTR) and thioredoxin are involved. The
      mutation of residue Glu-91 (E92 in spinach, E94 in Anabaena) alone, either to Gln
      (E91Q) or to Lys (E91K), was found to completely abolish the reaction of the
      enzyme light activation. On the other hand, the mutants (E92Q) or (E92K) were as
      efficient as the wild type ferredoxin in this reaction whereas the double mutants
      (E91Q/E92Q) or (E91K/E92K) had no activity. In addition, a triple mutant
      (D25A/E28Q/E29Q) was also found to be inactive for this redox dependent light
      activation. All these mutations had much weaker effects on the
      ferredoxin/ferredoxin NADP reductase interaction as measured by the cytochrome c
      reduction assay. These results indicate that there is a recognition site for FTR
      in the C terminus part of ferredoxin, but also that a core of negatively charged
      residues in the alpha1 helix of ferredoxin might be important in the general
      process of light activation.

PMID- 9009218
TI  - A structure prediction for the ligand-binding region of the integrin beta
      subunit: evidence for the presence of a von Willebrand factor A domain.
AB  - The integrins are a family of cell surface receptors that mediate biologically
      important adhesive interactions. Integrin-ligand binding has been extensively
      studied because of the potential for the development of anti-adhesive therapies,
      but the molecular basis of this interaction is still poorly understood. A
      conserved region near the N-terminus of the beta subunit appears to be of
      particular importance in ligand binding, but to date this domain has not been
      expressed in isolation. As a prelude to expression and potential structure
      determination, we have performed a detailed structure prediction for this region.
      Primary, secondary and tertiary structure analyses indicate that the region folds
      into a von Willebrand factor A-domain, thereby potentially placing a previously
      characterised module at the centre of a key functional region.

PMID- 9009219
TI  - Protein expression of the epsilon subspecies of protein kinase C ceases as Swiss
      3T6 fibroblasts increase in cell density even though message for the protein is
      still present.
AB  - We have noted previously that growth of C6 glioma cells from low cell density to
      confluency and quiescence in serum is accompanied by changes in protein content
      of different protein kinase C (PKC) subspecies. Here we show that the same occurs
      as non-contact-inhibiting Swiss 3T6 fibroblasts grow to high density in the
      presence of serum. Protein expression of PKC subspecies alpha and delta increases
      as the cells increase in density while that of PKC-zeta remains the same.
      Unusually, protein expression of PKC-epsilon is completely down-regulated as
      cells grow beyond about 50% confluency and no PKC-epsilon protein can be detected
      in 3T6 fibroblasts at high density by Western blotting. However, mRNA for PKC
      epsilon is expressed at all stages of fibroblast growth as revealed by RT-PCR.
      When high-density 3T6 fibroblasts are passaged to low density in fresh medium, re
      expression of PKC-epsilon protein is observed within 15 min and becomes down
      regulated again as cells become more dense. This very rapid synthesis of PKC
      epsilon is not blocked by the transcription inhibitor actinomycin D but is
      inhibited by cycloheximide. PKC-epsilon has some characteristics of a novel
      'early response' protein whose synthesis in newly passaged 3T6 cells is regulated
      at the translational level.

PMID- 9009220
TI  - Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic
      acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven
      nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32.
AB  - Using PCR-based techniques, we have isolated and sequenced the full-length cDNAs
      that encode the human neuronal nAChR subunits alpha3,4,5,7 and beta2,3,4 in the
      neuroblastoma cell lines SH-SY5Y and/or IMR-32. The predicted nAChR beta3- and
      beta4-subunit proteins contain 458 and 498 amino acids, respectively. Except for
      the beta2, all the other cloned cDNAs showed differences with the published
      sequences. Northern blots show expression of the nAChR subunits alpha3,7 and
      beta2,4 in the human neuroblastoma cell line SH-SY5Y, with intensity of the
      hybridisation signal decreasing in the order alpha3 > beta4 > beta2 > alpha7.

PMID- 9009222
TI  - Lymph node localisation of biodegradable nanospheres surface modified with
      poloxamer and poloxamine block co-polymers.
AB  - Studies were performed to develop a sub-100 nm biodegradable colloidal system for
      the efficient delivery of drugs and diagnostic agents to the lymphatic system.
      Nanospheres of poly(lactide-co-glycolide) were prepared by interfacial polymer
      deposition. The nanospheres were coated with block co-polymers in order to modify
      their surface characteristics. Radiolabelling of the nanospheres for in vivo
      tracing was achieved by the incorporation of the lipophilic complex 111In-oxine
      during nanosphere preparation. In vitro stability of the radiolabelled
      nanospheres was determined in rat serum at 37 degrees C. The lymphatic
      distribution of the nanospheres was determined after subcutaneous administration
      to the rat. Lymphatic uptake of all coated systems was enhanced compared to the
      uncoated nanospheres, and a maximal uptake of 17% of the administered dose in the
      regional lymph nodes was achieved. These observations suggest that the
      nanospheres are suitable for diagnostic and therapeutic applications in clinical
      and experimental medicine.

PMID- 9009221
TI  - Nuclear factor-kappaB activation in human monocytes stimulated with
      lipopolysaccharide is inhibited by fibroblast conditioned medium and exogenous
      PGE2.
AB  - The nuclear factor kappaB (NF-kappaB) is thought to be crucially involved in the
      gene activation of several cytokines, including tumor necrosis factor alpha
      (TNF). Previously, we showed that fibroblast conditioned medium (FCM) is able to
      inhibit both TNF mRNA accumulation and protein release in peripheral blood
      derived human monocytes (PBM) stimulated with lipopolysaccharide (LPS). In this
      study we have investigated the effect of FCM on the LPS-induced DNA-binding
      activity of NF-kappaB, by means of electrophoretic shift assay (EMSA). We provide
      evidence that FCM strongly inhibits the LPS-induced NF-kappaB activation in PBM.
      Furthermore, we show that exogenous PGE2 mimics the NF-kappaB inhibitory effect
      of FCM. On the other hand, FCM produced in the presence of indomethacin does not
      inhibit NF-kappaB activation by LPS. Our results lend further support to the
      hypothesis that inflammatory and immune responses of monocytes/macrophages may be
      modulated at the molecular level by signals originating from tissue structural
      cells such as fibroblasts.

PMID- 9009223
TI  - A calmodulin-stimulated Ca2+-ATPase from plant vacuolar membranes with a putative
      regulatory domain at its N-terminus.
AB  - A cDNA, BCA1, encoding a calmodulin-stimulated Ca2+-ATPase in the vacuolar
      membrane of cauliflower (Brassica oleracea) was isolated based on the sequence of
      tryptic peptides derived from the purified protein. The BCA1 cDNA shares sequence
      identity with animal plasma membrane Ca2+-ATPases and Arabidopsis thaliana ACA1,
      that encodes a putative Ca2+ pump in the chloroplast envelope. In contrast to the
      plasma membrane Ca2+-ATPases of animal cells, which have a calmodulin-binding
      domain situated in the carboxy-terminal end of the molecule, the calmodulin
      binding domain of BCA1 is situated at the amino terminus of the enzyme.

PMID- 9009224
TI  - Monocyte chemoattractant protein-2 can exert its effects through the MCP-1
      receptor (CC CKR2B).
AB  - We studied the activities of the monocyte chemoattractant proteins MCP-1, MCP-2
      and MCP-3 on human embryonic kidney 293-EBNA cells transfected with the MCP-1
      receptor (CC CKR2B). At 4 nM, MCP-2 induced a Ca2+ influx which was as potent as
      that with MCP-1 at 4 nM, although the increase by MCP-2 became saturated at
      higher concentrations. In addition, all three MCPs showed dose-dependent
      inhibition of adenylyl cyclase activity stimulated by forskolin (IC50 values: 0.3
      nM for MCP-1, 7 nM for MCP-2, and 1.5 nM for MCP-3). In conclusion, our data
      indicate that MCP-2 can exert its effects through the MCP-1 receptor, CC CKR2B.

PMID- 9009225
TI  - Purification of ADAM 10 from bovine spleen as a TNFalpha convertase.
AB  - We have purified a protease with characteristics of TNFalpha convertase from
      bovine spleen membranes. Peptide sequencing of the purified protein identified it
      as ADAM 10 (Genbank accession no. Z21961). This metalloprotease cleaves a
      recombinant proTNFalpha substrate to mature TNFalpha, and can cleave a synthetic
      peptide substrate to yield the mature TNFalpha amino terminus in vitro. The
      enzyme is sensitive to a hydroxamate inhibitor of MMPs, but insensitive to
      phosphoramidon. In addition, cloned ADAM 10 mediates proTNFalpha processing in a
      processing-incompetent cell line.

PMID- 9009226
TI  - Inhibition of carboxypeptidase A by excess zinc: analysis of the structural
      determinants by X-ray crystallography.
AB  - Pancreatic metallocarboxypeptidases are inhibited by a millimolar excess of zinc
      together with other exo- and endometalloproteases. We have analyzed the structure
      of bovine carboxypeptidase A inhibited by an excess of zinc ions using X-ray
      crystallography at 1.7 A overall resolution. Under these conditions, a second
      zinc is observed to bind to the enzyme active site, establishing a distorted
      tetrahedrally coordinated complex which involves Glu-270 (the general base for
      catalysis), a water molecule, a chloride ion, and a hydroxide ion. This hydroxide
      ion forms a 114 degrees angular bridge between the inhibitory and the catalytic
      zinc ions, which are at a distance of 3.3 A from one another. The inhibitory zinc
      holds the hydroxide at nearly the same location as a previously observed active
      site water molecule (W571) and probably perturbs the substrate positioning and
      stereochemical rearrangements required for substrate cleavage during catalysis.

PMID- 9009227
TI  - Inhibition of epithelial Na+ currents by intracellular domains of the cystic
      fibrosis transmembrane conductance regulator.
AB  - Cystic fibrosis is characterized by an impaired cyclic adenosine 3,5
      monophosphate (cAMP) activated Cl- conductance in parallel with an enhanced
      amiloride sensitive Na+ conductance (ENaC) of the respiratory epithelium. Very
      recently, acute downregulation of ENaC by the cystic fibrosis transmembrane
      conductance regulator (CFTR) was demonstrated in several studies. The mechanism,
      however, by which CFTR exerts its inhibitory effect on ENaC remains obscure. We
      demonstrate that cytosolic domains of human CFTR are sufficient to induce
      inhibition of rat epithelial Na+ currents (rENaC) when coexpressed in Xenopus
      oocytes and stimulated with 3-isobutyl-1-methylxanthine (IBMX). Moreover,
      mutations of CFTR, which occur in cystic fibrosis, abolish CFTR-dependent
      downregulation of rENaC. Yeast two hybrid analysis of CFTR domains and rENaC
      subunits suggest direct interaction between the proteins. Enhanced Na+ transport
      as found in the airways of cystic fibrosis patients is probably due to a lack of
      CFTR dependent downregulation of ENaC.

PMID- 9009228
TI  - Expression of a 26S proteasome ATPase subunit, MS73, in muscles that undergo
      developmentally programmed cell death, and its control by ecdysteroid hormones in
      the insect Manduca sexta.
AB  - MS73, an ATPase regulatory subunit of the 26S proteasome in the moth Manduca
      sexta, is shown to be expressed at a high level only in muscles that are
      undergoing developmentally programmed cell death, or which are destined to do so.
      The amount of MS73 is increased by more than two-fold just before death in each
      of three different muscles that die at different times, under different
      developmental controls. An ecdysteroid (moulting hormone) agonist, RH-5849, that
      prevents the occurrence of programmed cell death in two of these muscles also
      prevents the normally occurring rise in level of MS73 in these muscles. This
      evidence is consistent with a role for MS73 in programmed cell death.

PMID- 9009229
TI  - Rapid internalization of exogenous ganglioside GM3 and its metabolism to ceramide
      in human myelogenous leukemia HL-60 cells compared with control ganglioside GM1.
AB  - Incorporation and metabolism of exogenous GM3 in human myelogenous leukemia HL-60
      cells were analyzed using 3H-labeled GM3 ([3H]GM3). [3H]GM3 was rapidly
      internalized into the cells (trypsin-resistant fraction) 8 times more than the
      control, 3H-labeled GM1 ([3H]GM1). In addition, not only incorporation but also
      metabolism of [3H]GM3 was more rapid than [3H]GM1 in HL-60 cells. Moreover, one
      of the metabolites was found to co-migrate with ceramide in thin-layer
      chromatography analysis and ceramide formation from exogenous GM3 is more rapid
      than that from exogenous GM1. These results suggested that there would be some
      preferential mechanism to produce ceramide from differentiation-inducible GM3 in
      HL-60 cells rather than from non-inducing GM1.

PMID- 9009230
TI  - Fructan synthesis in transgenic tobacco and chicory plants expressing barley
      sucrose: fructan 6-fructosyltransferase.
AB  - We have recently cloned a cDNA encoding sucrose:fructan 6-fructosyltransferase (6
      SFT), a key enzyme of fructan synthesis forming the beta-2,6 linkages typical of
      the grass fructans, graminans and phleins [Sprenger et al. (1995) Proc. Natl.
      Acad. Sci. USA 92, 11652-11656]. Here we report functional expression of 6-SFT
      from barley in transgenic tobacco and chicory. Transformants of tobacco, a plant
      naturally unable to form fructans, synthesized the trisaccharide kestose and a
      series of unbranched fructans of the phlein type (beta-2,6 linkages).
      Transformants of chicory, a plant naturally producing only unbranched fructans of
      the inulin type (beta-2,1 linkages), synthesized in addition branched fructans of
      the graminan type, particularly the tetrasaccharide bifurcose which is also a
      main fructan in barley leaves.

PMID- 9009231
TI  - Role of carotene in the rapid turnover and assembly of photosystem II in
      Chlamydomonas reinhardtii.
AB  - Inhibitors of the phytoene desaturase in carotene biosynthesis were tested in the
      enhanced rapid turnover of the D1 protein of photosystem II in high light
      exposure of Chlamydomonas reinhardtii cells. After 1 h high light on
      heterotrophically grown cells in the presence of norflurazon or fluridone,
      photosynthesis activity in vivo and PS II activity in vitro is lost. The D1
      protein has disappeared. PS I activity is not affected, nor is the D2 protein. It
      is concluded that beta-carotene is essential for the assembly of the D1 protein
      into functional photosystem II. It is suspected that bleaching of beta-carotene
      in the reaction center of PS II by high light destabilizes the structure and
      triggers the degradation of the D1 protein.

PMID- 9009232
TI  - Sex steroids regulate the expression of plasminogen activator inhibitor-1 (PAI-1)
      and its mRNA in uterine endometrial cancer cell line Ishikawa.
AB  - To know the effects of sex steroids on the potentials of growth, invasion, and
      metastasis with neovascularization of endometrial cancer, the expression of
      plasminogen activator inhibitor (PAI)-1 [an inhibitor of tissue-type plasminogen
      activator (tPA) and urokinase-type plasminogen activator (uPA)] and its mRNA in
      well-differentiated uterine endometrial cancer cell line Ishikawa was determined
      by an enzyme-linked immunosorbent assay and reverse transcription-polymerase
      chain reaction-Southern blotting (RT-PCR-SB), respectively, under the influence
      of sex steroids. In Ishikawa cells, either estradiol or progestins (progesterone,
      medroxyprogesterone acetate, or 17 alpha-hydroxyprogesterone alone) induced the
      expression of PAI-1 and its mRNA, and those expressions were increased
      approximately two-fold by both estradiol and progestin administered together.
      Therefore, sex steroidal induction of PAI-1 might contribute to the inhibition of
      invasion and metastasis, concomitantly with the inhibition of neovascularization
      associated with tPA and uPA activities, in well differentiated endometrial
      cancer.

PMID- 9009233
TI  - Transcriptional activation and transient expression of the human androgen
      receptor.
AB  - A series of cDNAs containing deletions within the open-reading frame of the human
      androgen receptor (AR) were constructed and transiently expressed in CV1 cells to
      investigate the effects of these alterations on the level of expression of the
      protein and on its capacity to activate a model reporter gene (MMTV-luciferase).
      The levels of AR expression were assayed using immunoblots made using an antibody
      directed at an epitope (amino acids 1-21) preserved in all of the deletions.
      Treatment of the transfected cells with androgen increased the level of normal or
      mutant AR approximately five-fold in all constructs in which the hormone-binding
      domain was intact. This finding indicates that an intact hormone-binding domain
      is necessary and sufficient for the androgen-dependent increase in AR levels.
      Contraction of expansion or the glutamine repeat or deletion of the glycine
      repeat in the amino terminus diminished the capacity of the mutant ARs to
      activate the MMTV luciferase gene. The presence of a large-scale deletion within
      the amino terminus (amino acid residues 96-483), abolished receptor function, and
      two smaller deletions (bounded by residues 80-93 and 245-485) within the amino
      terminus substantially impaired receptor function. As previously described,
      deletion of the hormone-binding domain (amino acids 708-917) resulted in a
      constitutively active receptor. Unexpectedly, the large-scale deletion within the
      amino terminus (amino acids 96-483), in combination with deletion of the carboxy
      terminus also produced a constitutively active receptor that was almost as active
      as ligand-activated normal AR. None of the alterations in AR function could be
      explained by changes in the level of AR expression and the function of some
      mutant receptors was even more defective when the relative levels of mutant ARs
      expressed was considered. These findings imply that interaction of the sequences
      within the amino- and carboxy-terminal portions of the AR, or proteins that
      interact with these segments, is critical for regulation of transcription by the
      AR.

PMID- 9009234
TI  - 17alpha-Hydroxylase gene expression in the bovine ovary: mechanisms regulating
      expression differ from those in adrenal cells.
AB  - 17alpha-Hydroxylase cytochrome P450 (P450(17alpha)) is the enzyme which
      synthesizes C19 steroids in a two-step reaction in which 17alpha-OH pregnenolone
      is an intermediate. In the bovine and human adult female, 17alpha-hydroxylase is
      expressed in adrenocortical cells where 17alpha-OH pregnenolone and 17alpha-OH
      progesterone are precursors of cortisol, and in theca cells of the ovary where
      these intermediates are precursors of C19 steroids. In both adrenal cortex and
      theca, 17alpha-hydroxylase gene expression is stimulated by cyclic AMP (cAMP).
      The aim of this study was to determine the mechanism regulating 17alpha
      hydroxylase gene expression in the bovine ovary. Our results indicate that the
      bovine 17alpha-hydroxylase gene is regulated in a tissue-specific fashion. Primer
      extension and S1 nuclease protection assays reveal that the start site of
      transcription in the theca is identical to that in the adrenal. Transfection
      studies employing beta-globin reporter gene constructs fused to successive
      deletions of the 5' regulatory region of the bovine 17alpha-hydroxylase gene
      indicate that sequences between -80 and -37 basepairs (bp) (CRS2) confer cAMP
      regulated transcription in bovine theca cells in culture. These results are in
      contrast to similar studies conducted in bovine adrenocortical cells, which
      indicate that the major cAMP response element (referred to as CRS1) is located at
      -243 to -225 bp. The Ad4 element (AGGTCA, -42 to -37 bp) within CRS2, which has
      been shown to be involved in cAMP responsiveness in other steroidogenic P450
      genes, cannot by itself confer cAMP-regulated reporter gene expression in bovine
      cells. These results indicate that in the cow, 17alpha-hydroxylase gene
      expression is regulated in a tissue-specific fashion, and that this regulation
      may be conferred, at least in part, by the use of tissue-specific cis-acting
      elements in the bovine 17alpha-hydroxylase gene.

PMID- 9009235
TI  - Characterization of the functional progesterone receptor in an endometrial
      adenocarcinoma cell line (Ishikawa): progesterone-induced expression of the
      alpha1 integrin.
AB  - Endometrial progesterone receptors (PR) are regulated by both estrogen (E2) and
      progesterone (P) and mediate the expression of specific endometrial proteins.
      Ishikawa cells are a well-differentiated human endometrial adenocarcinoma cell
      line, with both estrogen receptors (ER) and PR, regulated in a manner similar to
      that of normal endometrium. Immunohistochemical and biochemical analyses
      demonstrate that the concentration of PR is increased by E2 priming and decreased
      by subsequent treatment with P. Scatchard plot analysis showed a K(d) of 1 nM. On
      the basis of biochemical analysis, PR concentrations reached approximately 1400
      fmol/mg cytosol protein in cells after treatment with E2 (10(-8) M) for 4 days.
      Immunoprecipitation and Western blot studies revealed the presence of both the
      116 kDa and 81 kDa proteins with multiple isoforms of the high molecular weight
      (MW) protein. Northern blot analysis demonstrated transcriptional control of PR
      by steroid treatment. These studies demonstrate the coordinate regulation of all
      PR mRNA species. The functionality of Ishikawa PR was demonstrated by the
      expression of alpha1beta1 integrin in response to E2 plus P, at the level of
      transcription and translation. This effect was blocked by the addition of the
      anti-progestin, RU-486. These studies reconfirm that the Ishikawa cell line is an
      excellent model for the study of hormonally regulated events in the human
      endometrial epithelium.

PMID- 9009236
TI  - Synthesis and sulfatase inhibitory activities of non-steroidal estrone sulfatase
      inhibitors.
AB  - About one-third of breast cancers are classified as estrogen-dependent breast
      cancers. In the past 10 years, numerous reports have suggested the importance of
      estrone sulfate and estrone sulfatase in regulating the supply of estrogens to
      these cancers. Estrone sulfatase inhibitors may thus prove to be useful for the
      treatment of these diseases. Several research groups have reported the
      development of estrone sulfatase inhibitors, and estrone-3-O-sulfamate has been
      shown to be the most potent sulfatase inhibitor. However, a recent report
      indicated that estrone may be released during the inactivation of sulfatase by
      estrone-3-O-sulfamate and rendered the inhibitor to be estrogenic. Therefore,
      there is a need for a potent non-steroidal sulfatase inhibitor that is
      metabolically stable, more selective, and lacking estrogenic activity. We
      developed a series of (p-O-sulfamoyl)-N-alkanoyl tyramines, and they proved to be
      potent estrone sulfatase inhibitors. Using human placental microsome as the
      enzyme source, the best inhibitor in this series, compound 18, has an IC50 of
      55.8 nM. Another potent inhibitor in this series, compound 17, exhibited time
      dependent inactivation of sulfatase when incubated at various concentrations (0.2
      1.0 microM) of the inhibitor. Estrone sulfate partially blocked the inactivation
      of the enzyme by the compound, indicating that the compound inactivated sulfatase
      at the active site. The irreversible nature of the enzyme-inhibitor interaction
      was supported by irreversibility studies. Thus, (p-O-sulfamoyl)-N-alkanoyl
      tyramines represent a new series of non-steroidal estrone sulfatase inhibitor.

PMID- 9009237
TI  - RU 3117 a steroidal compound with high affinity for sigma sites in rat testis
      membranes.
AB  - RU 3117 belongs to a new series of steroids which exhibited a high relative
      binding affinity (RBA) for (+)[3H]PPP sites in rat testis membranes; its RBA was
      about 40 times higher than that of progesterone. Furthermore, it is devoid of any
      binding to classical steroid receptors; therefore in order to study its binding
      parameters on rat testis membranes it was tritiated. [3H]RU 3117 bound at least
      two distinct sites with Ka values of 0.4 +/- 0.06 x 10(9) M(-1) and 1.3 +/- 0.2 x
      10(7) M(-1). Using this marker, competition studies with cold haloperidol showed
      that a part of this binding was haloperidol-sensitive, whereas another part was
      haloperidol-resistant. Interestingly, progesterone described as a sigma ligand
      competes with [3H]RU 3117 binding, with an RBA of 1.6%. When haloperidol was
      preincubated (250 nM) with rat testis membranes, in order to mask the sigma
      sites, we observed that DTG (1,3-di-O-tolylguanidine) and haloperidol displayed a
      very low RBA (< 0.1%) and were not able totally to displace the [3H]RU 3117
      binding up to 50 microM. Furthermore, benztropine exhibited a significant RBA of
      19% but its displacement curve showed a plateau (500-50,000 nM). These results
      showed that part of the haloperidol-resistant sites was benztropine sensitive but
      another part was displaced neither by haloperidol nor by benztropine. The
      presence of these remaining binding sites was confirmed by preincubating a
      mixture of haloperidol and benztropine with testis membranes. Under these
      conditions, [3H]RU 3117 displayed a Ka of 1.0 +/- 0.01 x 10(7) M(-1), and we
      observed that these sites were recognized, up to now, only by the steroids RU
      1968 and RU 54173 which are also devoid of any binding to classical nuclear
      steroid receptors.

PMID- 9009238
TI  - Equine cytochrome P450 aromatase exhibits an estrogen 2-hydroxylase activity in
      vitro.
AB  - Aromatase (estrogen synthetase) is a steroidogenic enzyme complex which catalyzes
      the conversion of androgens to estrogens (termed aromatization). This enzyme was
      purified from adult equine testis to homogeneity by five chromatographic steps.
      The ability of purified and reconstituted equine aromatase to exhibit an estrogen
      2-hydroxylase activity was tested and compared to testosterone aromatization.
      Enzymatic activities were assessed by tritiated water release from labelled
      estradiol and testosterone. Kinetic analysis of estradiol 2-hydroxylation showed
      an apparent K(m) of 23 microM and a V(max) of 18 nmol/min/mg, whereas the values
      for testosterone aromatization were a K(m) of 15.7 nM and a V(max) of 34.6
      pmol/min/mg. A specific antiserum raised against purified testicular equine
      P450arom and known to inhibit aromatase activity [1] was also found to inhibit
      the estrogen hydroxylase activity of equine placental microsomes in a dose
      dependent manner with an IC50 value of 15 microl serum: 0.5 ml incubate. The
      estrogen hydroxylase activity was inhibited in a dose-dependent manner by two
      classes of aromatase inhibitors, i.e. steroidal-- (4-hydroxyandrostenedione and
      7alpha-([4-aminophenyl]thio)-androst-4-ene-3, 17-dione)--and non-steroidal-
      (fadrozole and miconazole). The IC50 values were approximately 300 and 890 nM for
      4-hydroxyandrostenedione and 7alpha-([4-aminophenyl]thio)-androst-4-ene-3, 17
      dione, and 92 and 285 nM, for fadrozole and miconazole, respectively.
      Furthermore, 4-hydroxyandrostenedione caused a time-dependent inactivation of
      estrogen hydroxylase activity. We conclude that equine aromatase is able to use
      estradiol as a substrate, and converts it to catechol estradiol in vitro,
      possibly using the active site of aromatization. This is the first demonstration
      that equine aromatase functions as an estrogen 2-hydroxylase, in addition to
      transforming androgens into estrogen.

PMID- 9009239
TI  - RU 38486 inhibits intracellular calcium mobilization and PGI2 release from human
      myometrium: mechanisms of action.
AB  - We previously demonstrated that the antiprogestogen RU 486, when superfused on
      myometrial strips, induces a rapid decrease in spontaneous uterine contractile
      frequency, an increase in amplitude and duration of contractions, and a
      concomitant decrease in 6-keto PGF(1alpha) release. In this study, we present
      further work on the role of calcium transients and the involvement of the PLC/PKC
      pathway in mediating RU 486 effects. We found no clear causal relationship
      between the spontaneous contractility controlled by external Ca++ concentration
      and 6-keto PGF(1alpha) release depending mostly on intracellular Ca++
      mobilization. We show that RU 486 strengthened the inhibitory effect of TMB8, a
      potent inhibitor of internal calcium, on both spontaneous contractility and 6
      keto PGF(1alpha), release and antagonized the stimulatory action of thapsigargin,
      a toxin blocking the endoplasmic reticulum calcium pump (ER Ca++ ATPase). These
      data indicate that RU 486 could act as an inhibitor of intracellular Ca++
      mobilization. A slight but significant decrease of the prostanoid liberation was
      observed in the presence of U73122, an inhibitor of PLC, but not in the presence
      of neomycin, another PLC inhibitory compound. PKC inhibitors, staurosporine and
      H7 did not significantly affect spontaneous 6-keto PGF1alpha release, showing
      that PIP2 hydrolysis and PKC pathway were not involved in the basal release of
      the prostacyclin metabolite. Vasopressin (AVP), an agent known to induce
      contractility of the non-pregnant human uterus, markedly increased 6-keto
      PGF(1alpha) release in a dose-dependent manner. Stimulation of GTP-regulated
      proteins (G proteins) by ALF4 was accompanied by a rise in 6-keto PGF(1alpha)
      liberation and a high contractile activity. The effects of both vasopressin and
      ALF4- were not significantly opposed by RU 486, indicating that other sources of
      Ca++, not controlled by the steroid, were involved in the agonist-stimulated
      prostanoid release. Studies with structurally related RU 486 analogues showed
      that the steroid effects were not dependent on their antihormonal activity, but
      rather on a specific 11beta arylsubstitution and a 17beta-hydroxy-13beta-methyl
      configuration of the 4,9-estradien-3-one molecule.

PMID- 9009240
TI  - The antiovulatory activity of progesterone antagonists is not correlated to their
      antiprogestational potency in the rat.
AB  - Progesterone antagonists often differ in regard to their potency to block
      ovulation in rats although they may possess similar 'antiprogestational'
      (abortive) activity. Therefore, the questions arose as to: (a) whether
      antiovulatory and antiprogestational effects (on endometrial and mammary gland
      parameters) of antiprogestins correlate at all; and (b) which mechanism(s) may be
      responsible for their ability to abolish ovulation. To answer these questions we
      set out to compare the influences of two progesterone antagonists, Onapristone
      (ON) a very potent and ZK 136798 only a weak inhibitor of ovulation, to assess
      changes on the one hand on typical progestational actions and on the other hand
      on factors known to regulate ovulation. For this purpose immature PMSG/hCG primed
      and adult female rats and infantile female rabbits were treated either with ON,
      ZK 136798 or vehicle in different treatment schedules. In these investigations ON
      and ZK 136798 showed similar antiprogestational activities on the progesterone
      induced development of mammary glands (rats) and the secretory transformation of
      endometrium (rabbits). ON blocked an induced or a spontaneous ovulation, whereas
      ZK 136798 only revealed a very weak antiovulatory effect. Both ON and ZK 136798
      stimulated basal levels of LH, estradiol, and testosterone, whereas the
      preovulatory LH surge was decreased to the same extent. Interestingly, in
      contrast to ZK 136798, ON reduced the preovulatory increase in progesterone
      secretion. These results clearly indicate: (a) that antiovulatory potency and
      antiprogestational activity may not be correlated in the rat; and (b) that
      decreased preovulatory levels of progesterone following treatment with ON may
      play an important role in intraovarian mechanism(s) contributing to a blocking of
      ovulation.

PMID- 9009241
TI  - Inhibition of placental estrone sulfatase activity and MCF-7 breast cancer cell
      proliferation by estrone-3-amino derivatives.
AB  - Estrogen levels in breast tumors of post-menopausal women are as much as 10 times
      higher than in plasma, presumably due to in situ formation of estrogen. Several
      lines of evidence indicate that the major source of estrogen in breast cancer
      cells may be from conversion of estrone sulfate to estrone by the enzyme estrone
      sulfatase. Inhibitors of estrone sulfatase may thus be potential agents for the
      treatment of estrogen-dependent breast cancer. We designed and synthesized a
      series of estrone-3-amino derivatives as potential estrone sulfatase inhibitors.
      We tested the inhibitory potential of these compounds using human placental
      microsomes, which contain a substantial amount of estrone sulfatase activity.
      Several compounds in the series significantly inhibited estrone sulfatase
      activity of the human placental microsomes when present at 10 microM. The IC50
      for the estrone-3-amino compounds ranged from 8.7 to 14.6 microM. We next tested
      the ability of the estrone-3-amino derivatives to inhibit growth of the estrogen
      dependent MCF-7 breast cancer cell line. MCF-7 cells showed substantial
      proliferation in the presence of 100 nM estrone sulfate in estrogen-free media,
      indicating that the cells were capable of converting estrone sulfate into
      estrone. The proliferative effect of estrone sulfate (1 microM) was significantly
      blocked by the estrone-3-amino derivatives at 10 microM. The magnitude of MCF-7
      cell inhibition resulting from treatment with the estrone-3 amino compounds was
      similar to or exceeded that of Danazol, but was less than the level resulting
      from treatment with estrone sulfamate. Using data from all of the compounds
      tested, inhibition of MCF-7 cell proliferation was positively correlated with
      inhibition of placental estrone sulfatase activity, suggesting that the reduction
      in cell growth was attributable to the blockade of sulfatase activity. In support
      of this, there was no relationship between inhibition of estrone sulfatase
      activity and inhibition of cell growth when the estrogen-independent cell line
      MDA-MB-231 was used. Our results indicate the possible utility of estrone-3-amino
      derivatives for inhibition of estrone sulfatase activity. Further, our data
      support the concept that estrone sulfatase inhibitors may be useful as
      therapeutic agents for estrogen-dependent breast cancers.

PMID- 9009242
TI  - 7alpha-Arylaliphatic androsta-1,4-diene-3,17-diones as enzyme-activated
      irreversible inhibitors of aromatase.
AB  - Inhibition of aromatase, the enzyme responsible for converting androgens to
      estrogens, may be therapeutically useful for the endocrine treatment of hormone
      dependent breast cancer. Previous research on 7alpha-thiosubstituted androgens,
      especially 7alpha-(4'-aminophenylthio)-androsta-1,4-diene-3,17-di one, has shown
      that these compounds are potent enzyme-activated irreversible inhibitors of
      aromatase. Research on the synthesis of more metabolically stable inhibitors has
      focused on replacing the thioether linkage at the 7alpha position with a carbon
      carbon linkage. Several 7alpha-arylaliphatic androst-4-ene-3,17-diones were
      previously shown to be potent competitive inhibitors of aromatase. The extension
      of the research on these 7alpha-arylaliphatic androgens includes the introduction
      of a C1-C2 double bond in the A-ring to provide enzyme-activated irreversible
      inhibitors. The desired 7alpha-arylaliphatic androsta-1,4-diene-3,17-diones were
      obtained from their corresponding 7alpha-arylaliphatic androst-4-ene-3,17-diones
      by oxidation using DDQ. A new improved synthesis of the 7alpha-arylaliphatic
      androst-4-ene-3,17-diones using an in situ preparation of the CuI-(n-Bu3)P
      complex was employed. The aryl ring of the 7alpha-phenethyl and 7alpha-phenpropyl
      derivatives were functionalized to their corresponding p-nitro and p-amino
      derivatives. These compounds were all potent inhibitors of aromatase with
      apparent K(i)s ranging between 7 and 19 nM. These inhibitors demonstrated enzyme
      mediated inactivation of aromatase with apparent k(inact)s ranging from 4.4 x 10(
      4) to 1.90 x 10(-3)/s. The best inactivator of the series was the 7alpha
      phenpropylandrosta-1,4-diene-3,17-dione, which exhibited a T(1/2) of 6.08 min.

PMID- 9009243
TI  - Synthesis, structure and biological properties of Z-17alpha-(2-iodovinyl)-11beta
      chloromethyl estradiol-17beta (Z-CMIV), a high affinity ligand for the
      characterization of estrogen receptor-positive tumors.
AB  - Linkage of a 11beta-chloromethyl group to estradiol-17beta (E2) dramatically
      increases the binding affinity of the steroid for the estrogen receptor (ER) with
      the formation of a quasi-irreversible steroid-receptor complex. We have
      synthesized the two isomers of 11beta-chloromethyl-17alpha-iodovinyl-estradiol (E
      CMIV and Z-CMIV) by a novel route. Both derivatives demonstrated high binding
      affinity and selectivity for ER (RBAs: ER = 820 and 1008; SHBG = 1.2 and 0.25,
      respectively; E2 = 100). On the basis of X-ray crystallographic data for Z-CMIV
      and its precursor, we have postulated that Z-CMIV might interact strongly with
      aromatic amino-acids within a hydrophobic groove of the ER hormone binding domain
      (HBD) that incorporates pockets corresponding to the 11beta and 17alpha steroid
      substituents. The binding properties of Z-CMIV labeled with 125I were
      investigated, especially its ability to detect and quantify altered ER forms with
      low binding affinity for E2. Sucrose density gradient analysis revealed that Z
      CMIV has a higher activation potency than E2 as it converts a higher proportion
      of non-activated monomers in the cytosol into activated monomers with the
      potential to dimerize. In in vitro (MCF-7 cells) and in vivo (rat uterus)
      determinations of estrogenic activity, Z-CMIV was as potent as E2 in increasing
      progesterone receptor (PgR) concentrations and decreasing ER levels and in
      stimulating uterine growth. [125I]-Z-CMIV could open the way to new applications
      in the diagnosis and therapy of ER-positive breast cancers, especially those
      containing altered (variant) ERs.

PMID- 9009244
TI  - The myelodysplastic syndromes in 1996: complex stem cell disorders confounded by
      dual actions of cytokines.
AB  - Based upon recent studies of apoptosis, proliferation, cytokines and genic
      abnormalities, a new hypothesis regarding the pathology of myelodysplastic
      syndromes is being proposed. The transforming abnormality which affects an early
      progenitor hemopoietic stem cell is poorly defined so far but confers a growth
      advantage on this cell eventually leading to monoclonal hemopoiesis at least
      affecting the non-lymphoid bone marrow cells. Several cytokines confound the
      picture by exerting dual effects of stimulating the proliferation of immature
      cells while inducing the apoptosis in their maturing progeny thereby producing
      the clinical syndrome of cytopenias despite cellular marrows. Since a number of
      these offending cytokines share the same common lipid intracellular signalling
      pathway, interfering with the generation of specific phospholipid second
      messengers should hypothetically result in a dual effect as well. Alleviation of
      cytopenias (due to attenuation of apoptosis) should be accompanied by a decrease
      in the progeny of the transformed stem cell (due to suppression of proliferation)
      eventually allowing for resumption of polyclonal hemopoiesis.

PMID- 9009245
TI  - Measurement of apoptosis, proliferation and three cytokines in 46 patients with
      myelodysplastic syndromes.
AB  - Extensive apoptosis or programmed cell death (PCD) of both hematopoietic
      (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysplastic
      syndromes (MDS) cancels the high birth-rate resulting in ineffective
      hematopoiesis and has been demonstrated as the probable basis for peripheral
      cytopenias in MDS by our group. It is proposed that factors present in the
      microenvironment are inducing apoptosis in all the cells whether stromal or
      parenchymal. To investigate this hypothesis further, bone marrow biopsies from 46
      MDS patients and eight normal individuals were examined for the presence of three
      cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor
      beta (TGF-beta) and granulocyte macrophage-colony stimulating factor (GM-CSF) and
      one cellular component, macrophages, by the use of monoclonal antibodies
      immunohistochemically. Results showed the presence of TNF-alpha and TGF-beta in
      41/46 and 40/46 cases of MDS respectively, while only 15 cases showed the
      presence of GM-CSF. Further a significant direct relationship was found between
      the degree of TNF-alpha and the incidence of PCD (p= 0.0015). Patients who showed
      high PCD also had an elevated TNF-alpha level. Thus, the expression of high
      amounts of TNF-alpha and TGF-beta and low amounts of the viability factor GM-CSF
      may be responsible for the high incidence of PCD leading to ineffective
      hematopoiesis in MDS. Future studies will be directed at attempting to reverse
      the lesion in MDS by using anti-TNF-alpha drugs such as pentoxifylline.

PMID- 9009246
TI  - RAS gene mutations in Chinese leukaemia patients and members of a family with
      high incidence of leukaemia.
AB  - We investigated mutations of N-RAS and K-RAS by using polymerase chain reaction
      (PCR)-oligonucleotide hybridization techniques in 40 cases of Chinese leukaemia
      patients and 17 presently healthy members of a family with high incidence of
      acute myeloid leukaemia. The results showed only two patients carried the
      mutation in codon 12 of N-RAS. Strikingly, however, in both cases the
      malignancies involved lymphoid lineage. There was no hereditary RAS mutation in
      the members of the remarkable family.

PMID- 9009248
TI  - The value of the monoclonal antibody, DBA44, in the diagnosis of B-lymphoid
      disorders.
AB  - The DBA44 monoclonal antibody described by Al Saati recognizes a membrane antigen
      expressed by a sub-population of B-lymphocytes. It was tested on paraffin
      embedded tissues, and it distinguishes Hairy Cell Leukemia (HCL) from the more
      common B-cell Chronic Lymphocytic Leukemia (CLL). Neither Splenic Lymphoma with
      Villous Lymphocytes (SLVL) cases nor Prolymphocytic Leukemia (PLL) cases were
      tested. We have tested 87 B-lymphoproliferative disorders with DBA44 on
      cytocentrifuge preparations. All five HCL cases were positive (100%). Of 24 cases
      of SLVL, 19 were positive (79%); of 58 other B-cell malignancies, five cases were
      positive (8.5%), including 1/8 CD5- CLLs, 1/5 PLLs and 3/24 lymphomas. All CD5+
      CLL were negative. DBA44 positivity cannot distinguish HCL from SLVL, which is
      the disease that may create major diagnostic problems. In contrast, when we
      compare SLVL to CLL (which is another diagnostic problem), significant
      differences were found between the incidence of DBA44 positivity in SLVL and both
      CD5+ B-CLL (p< 10(-5)), and CD5- B-CLL (p< 0.01). The monoclonal antibody DBA44
      is positive in HCL and SLVL. It is not helpful in the differential diagnosis of
      HCL and SLVL. In contrast, when a diagnostic problem arises between SLVL and CLL,
      the reactivity of DBA44 is of great value.

PMID- 9009247
TI  - Extramedullary blast crisis in chronic myeloid leukemia.
AB  - Among 235 patients with CML we reviewed 91 patients with BC diagnosed between
      1980 and 1995; 15 of the 91 (16%) developed extramedullary disease (EMD). The
      sites involved were the lymph nodes (13/15), CNS (1/15) and suborbital mass
      (1/15). The appearance of EMD was associated with chronic phase (CP) features in
      the bone marrow in 3/15 cases, with accelerated phase (AP) in 3/15 and with BC in
      9/15. 11/15 (73%) cases of EMD were classified as myeloid (My-EMD) and 4/15 as
      lymphoid-type (Ly-EMD): three B-phenotype and one T-phenotype. All Ly-EMD cases
      were treated with vincristine, daunorubicin and prednisone and obtained complete
      remission (CR). Cases of My-EMD were treated with daunorubicin and cytosine
      arabinoside, of which only 1/11 achieved CR. We suggest that in EMD also, the
      type, lymphoid or myeloid, of BC has a bearing on treatment response and
      prognosis: Ly-EMD is more responsive to treatment and has longer survival than My
      EMD.

PMID- 9009249
TI  - Effect of stem cell factor on leukemic progenitor cell growth and sensitivity to
      cytosine-arabinoside.
AB  - Recruitment of quiescent, clonogenic blasts from patients with acute myeloid
      leukemia (AML) by hematopoietic growth factors (HGFs) may improve the cytotoxic
      effects of cell-cycle-specific drugs like cytosine-arabinoside (Ara-C). Using the
      culture methods described by Nara and McCulloch and making a distinction between
      self-renewing and post-deterministic mitoses, we analyzed the effects of stem
      cell factor (SCF), a growth factor acting on early hematopoietic progenitor and
      stem cells. First, we demonstrated that SCF, used in combination with other HGFs
      included in fetal calf serum (FCS) and/or in 5637 cell line supernatant (5637
      CM), stimulated both colony formation and self-renewal of blast progenitors from
      10 patients, unlike SCF alone. We tested the effects of SCF on the recruitment of
      cells in the S-phase by using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining
      method in flow cytometry (FCM). We showed that SCF stimulated proliferation of
      AML cells significantly in 9/18 patients with AML. Second, we tested the
      influence of SCF on the sensitivity to Ara-C of self-renewing leukemic cells from
      18 patients with AML. We showed that SCF was efficient in increasing the toxicity
      of Ara-C on the self-renewing blast progenitors, especially with high
      concentrations of Ara-C. However, a large patient-to-patient heterogeneity was
      found and the activity of SCF was not correlated with its effect on the cell
      cycle. These data indicate that SCF can enhance sensitivity to Ara-C of some
      leukemic cells with self-renewing capacity.

PMID- 9009250
TI  - Enhanced delivery of synthetic oligonucleotides to human leukaemic cells by
      liposomes and immunoliposomes.
AB  - The ability of pH-sensitive liposomes and immunoliposomes to deliver synthetic
      antisense oligonucleotides (oligos) into human myeloid and lymphoid leukaemia
      cells was examined. The cellular uptake of an 18mer anti-myb oligonucleotide
      encapsulated in liposomes was from three- to five-fold higher than that of 32P
      oligos alone. In addition, anti-CD32 or anti-CD2 immunoliposomes improved the
      delivery of oligos to leukaemic cells carrying the appropriate receptor for the
      specific antibody-linked immunoliposome. The uptake of oligos was twice that of
      the liposome or non-specific immunoliposome encapsulated oligos. These findings
      support the use of liposomes or immunoliposomes to deliver antisense oligos into
      human leukaemic cells.

PMID- 9009251
TI  - Characterization of newly established human myeloid leukemia cell line (KF-19)
      and its drug resistant sublines.
AB  - A new human myeloid leukemia cell line, designated KF-19, and its drug resistant
      sublines have been established. The KF-19 cell line was established from the
      pericardial effusion of a patient with acute myeloid leukemia clinically
      resistant to chemotherapy and KF-19 cells were characterized by expression of
      myeloid markers and differentiation into neutrophil- and macrophage-like cells
      upon optimal stimulations. KF-19AraC, KF-19ADR and KF-19VCR were established as
      sublines resistant to cytosine arabinoside (AraC), adriamycin (ADR) and
      vincristine (VCR), respectively. Efflux of the corresponding drugs was documented
      in each cell line. Expression of the MDR1 gene and the P-glycoprotein was found
      only in KF-19ADR, which showed a cross resistance to anthracyclines and vinca
      alkaloids; this resistance was reversed by verapamil or cyclosporin A. KF-19VCR
      lacking MDR1 gene and P-glycoprotein expression showed only resistance to vinca
      alkaloids, which was partially reversed by verapamil and cyclosporin A.
      Unexpectedly, KF-19ADR and KF-19VCR displayed cross resistance to AraC, despite
      lack of alterations of deoxycytidine kinase (dCK) and deaminase (dA) activities.
      KF-19AraC showed an efflux of AraC as well as a decreased level of dCK, but not
      of dA. In addition, KF-19AraC showed cross resistance to VCR in the efflux assay.
      The cell lines reported herein will provide new aspects on the mechanisms of drug
      resistance in leukemic cells.

PMID- 9009252
TI  - Failure of cyclosporine to induce graft-vs-host disease or graft-vs-leukemia
      after syngeneic bone marrow transplantation in mice.
AB  - Cyclosporine administration can result in graft-vs-host disease (GVHD) after
      syngeneic or autologous bone marrow transplantation (BMT). However, data on its
      anti-tumor effects are limited. We have tried to produce cyclosporine-induced
      GVHD or graft-vs-leukemia (GVL) against two Ia-bearing murine leukemias. BALB/c
      mice undergoing syngeneic BMT after total-body irradiation received 1 mg/kg or 10
      mg/kg cyclosporine or dextrose intraperitoneally for 30 days post-transplant,
      followed by 5 x 10(3) BCL1 murine leukemia cells 1 or 3 weeks after stopping
      cyclosporine. Similarly, SJL/J mice undergoing syngeneic BMT received 10 mg/kg
      cyclosporine or dextrose intraperitoneally for 30 days post-transplant, and were
      inoculated with 5 x 10(3) or 10(5) murine acute myeloid leukemia (mAML) cells 3
      weeks after stopping cyclosporine. No clinical or histological evidence of GVHD
      was seen, and leukemia-free and overall survival was similar with cyclosporine
      and dextrose. We conclude that under the experimental conditions used, it is not
      possible to induce syngeneic GVHD with cyclosporine in BALB/c or SJL/J mice. In
      the absence of GVHD, this approach is also not associated with any GVL effect
      against murine leukemias BCL1 and mAML.

PMID- 9009253
TI  - The effect of edelfosine on CTP:cholinephosphate cytidylyltransferase activity in
      leukemic cell lines.
AB  - Analogs of ether phospholipids have been shown to have selective anti-neoplastic
      activity. The compounds are known to inhibit phospholipid biosynthesis. This
      paper examines the effect of the alkyl-lysophospholipid, edelfosine, on the rate
      limiting enzyme, CTP:cholinephosphate cytidylyltransferase, in de novo
      phosphatidylcholine synthesis in sensitive and resistant leukemic cell lines.
      Enzyme activity was measured by the incorporation of 14C-phosphocholine into CDP
      choline by lysates of HL60 and K562; cells demonstrated inhibition of
      incorporation of 14C-phosphocholine in HL60 cell lysates but no inhibition in
      K562 lysates. Partial purification of cytidylyltransferase by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting
      demonstrated similarity between the enzyme isolated from each cell line. Cloning
      and sequencing of cytidylyltransferase cDNA of HL60 cells was accomplished using
      a probe encoding the entire protein sequence of the K562 cytidylyltransferase
      gene. A substitution at nucleotide 751 from A in the HL60 cell cDNA clone to G in
      the K562 cDNA clone resulted in a change in amino acid number 251 from lysine
      (positively charged) in the HL60 enzyme to glutamic acid (negatively charged) in
      the K562 enzyme. This negative charge in the lipid-binding domain of the K562
      enzyme may result in a weaker binding of edelfosine and the observed decrease in
      activity, as evidenced by resistance to edelfosine by K562 cells.

PMID- 9009255
TI  - Isolation and phenotypic characterization of CD117-positive cells.
AB  - Mononuclear cells derived from cord blood were stained using the CD1 17-specific,
      fluorochrome-labeled monoclonal mouse antibody 95C3. Additional staining was
      performed using an isotype-specific rat-anti-mouse antibody, labeled with
      supermagnetic microparticles. Target cells were enriched by the technique of
      magnetic cell separation, MACS. The resulting cell population contained 96.5% (+/
      1.7% S.D.) CD1 17-expressing cells (n = 12) with different levels of CD117
      antigen expression. Using flow cytometry, two cell populations differing in size
      were found. A majority (93%) of cells with high forward scatter revealed a
      phenotype positive for CD117 and CD34. Isolated cells revealed a high fraction of
      hematopoietic progenitors (16%). The technique presented allows for an
      alternative approach of stem cell enrichment and might be useful in autologous
      transplantation of cells with hematopoietic properties.

PMID- 9009254
TI  - Reactivity of anti-AraC-resistant cell monoclonal antibody, YU-311, in formalin
      fixed paraffin-embedded specimens of various hematopoietic disorders.
AB  - YU-311 is a monoclonal antibody reacting with cytosine arabinoside (AraC)
      resistant human leukemic cell line and identifies a 92 kDa membrane protein. We
      have examined YU-311 reactivity with various hematopoietic disorders by an
      immunohistochemical method and evaluated a correlation between YU-311 expression
      and refractoriness to chemotherapy, retrospectively. YU-311 reacted with AraC
      resistant human leukemia cell lines, in which a 92 kDa membrane protein was
      identified by Western blotting, whereas drug-resistant cell lines to other than
      AraC failed to express YU-311 antigen. The frequency of YU-311 positivity was
      significantly increased in relapsed cases. Only five cases were positive for YU
      311 at diagnosis and 24 cases at relapse. Unexpectedly, only eight cases of
      relapsed leukemia/lymphoma expressed YU-311 and P-glycoprotein simultaneously.
      Most of the YU-311-positive relapsed cases showed clinical refractoriness for
      chemotherapy and then failed to induct complete remission or relapsed at short
      periods with short disease-free duration. These findings indicate that YU-311
      expression is closely associated with some aspects of drug resistance, especially
      with AraC resistance.

PMID- 9009256
TI  - Results of treatment with an intensive induction regimen using idarubicin in
      combination with cytarabine and etoposide in children with acute myeloblastic
      leukemia.
AB  - We report results achieved in our institution with a study opened in July 1990
      (similar to the German AML-BFM-87 in which daunorubicin was replaced by
      idarubicin in the induction phase and cranial preventive radiotherapy was
      omitted) and closed in December 1994, for the treatment of newly diagnosed acute
      myeloblastic leukemia (AML), without prior malignancies except for
      myelodysplasia. This evaluation included 68 patients, whose mean age was 6 years
      (range: 1 month-16 years). Thirty-nine were boys and 29 were girls. Complete
      remission rate was 80.9% (55/68), death on induction rate was 14.7% and induction
      failure rate was 4.4%. At median follow up of 38 months (range: 12-66 months),
      the 4-year event-free survival (EFS) estimate was 0.428 (S.E.: 0.062), event-free
      interval (EFI) estimate was 0.529 (S.E.: 0.07) and overall survival (OS) estimate
      was 0.44 (S.E.: 0.071). We conclude that idarubicin in combination with
      cytarabine and etoposide is a highly effective regimen for induction in children
      with AML. Although preventive cranial irradiation was not delivered, we have
      observed only one combined CNS relapse. Finally, we corroborate that in this
      setting two definite risk groups may be identified in children with AML.

PMID- 9009257
TI  - A child case of CD34+, CD33-, HLA-DR-, CD7+, CD56+ stem cell leukemia with thymic
      involvement.
AB  - It has been reported that the CD56+/CD7+/CD3- phenotype of natural killer (NK)
      cells develop from the CD34+/HLA-DR- bone marrow (BM) mononuclear cell population
      in long-term BM culture (LTBMC). An HLA-DR-/CD33+/CD56+/CD16- myeloid/natural
      killer cell acute leukemia has been described. We report here a 7-year-old boy
      who developed stem cell acute leukemia with superior vena cava syndrome secondary
      to thymic involvement. Surface marker analyses revealed that the leukemia cells
      showed CD34+/HLA-DR-/CD33-/CD7+/CD56+ phenotype. When stimulated with phorbol
      ester in vitro the leukemic cells morphologically differentiated to myeloid cells
      developing CD13, CD15 and CD56 antigens. Our results suggest that CD34+/HLA-DR
      /CD7+/CD56+ stem cell leukemia may arise from transformation of a pluripotent
      precursor cell, which could differentiate to both myeloid and NK cell lineages.

PMID- 9009259
TI  - Purging effect of dibutyl phthalate on leukemic cells associated with apoptosis.
AB  - Dibutyl phthalate (DBP) showed preferential suppression of the growth of leukemic
      cells and could be used as a purging agent for autologous bone marrow
      transplantation in the treatment of leukemia. With in vitro exposure of leukemic
      cells to DBP, most characteristic changes in morphology of apoptosis could be
      observed by electron microscopy while DNA degraded in this fashion gave a
      'ladder' pattern on DNA gel electrophoresis. The obtained results demonstrated
      that the purging effect of DBP on leukemic cells is mediated, at least in part,
      by the induction of apoptosis.

PMID- 9009258
TI  - Translocation (9;17) a novel translocation in acute myeloid leukaemia.
AB  - We report a case of AML, acute myeloid leukaemia, with a novel translocation
      involving the short arms of chromosomes 9 and 17. The acute myeloid leukaemia was
      morphologically classified as FAB subtype M2. A prolonged remission was induced
      with chemotherapy, followed by a relapse which was associated with the finding of
      the same translocation.

PMID- 9009260
TI  - Comparison of haematological recovery kinetics after myeloablative therapy
      between sibling allogeneic bone marrow and peripheral blood progenitor cell
      transplantation in the same adult acute lymphoblastic leukaemia patient.

PMID- 9009261
TI  - Diffuse large cell lymphoma presenting as inflammatory bowel disease in an
      adolescent with ataxia telangiectasia.

PMID- 9009262
TI  - The crystal structure of Escherichia coli maltodextrin phosphorylase provides an
      explanation for the activity without control in this basic archetype of a
      phosphorylase.
AB  - In animals, glycogen phosphorylase (GP) exists in an inactive (T state) and an
      active (R state) equilibrium that can be altered by allosteric effectors or
      covalent modification. In Escherichia coli, the activity of maltodextrin
      phosphorylase (MalP) is controlled by induction at the level of gene expression,
      and the enzyme exhibits no regulatory properties. We report the crystal structure
      of E. coli maltodextrin phosphorylase refined to 2.4 A resolution. The molecule
      consists of a dimer with 796 amino acids per monomer, with 46% sequence identity
      to the mammalian enzyme. The overall structure of MalP shows a similar fold to GP
      and the catalytic sites are highly conserved. However, the relative orientation
      of the two subunits in E. coli MalP is different from both the T and R state GP
      structures, and there are significant changes at the subunit-subunit interfaces.
      The sequence changes result in loss of each of the control sites present in
      rabbit muscle GP. As a result of the changes at the subunit interface, the 280s
      loop, which in T state GP acts as a gate to control access to the catalytic site,
      is held in an open conformation in MalP. The open access to the conserved
      catalytic site provides an explanation for the activity without control in this
      basic archetype of a phosphorylase.

PMID- 9009263
TI  - The small GTP binding protein rab7 is essential for cellular vacuolation induced
      by Helicobacter pylori cytotoxin.
AB  - The VacA cytotoxin, produced by toxigenic strains of Helicobacter pylori, induces
      the formation of large vacuoles highly enriched in the small GTPase rab7. To
      probe the role of rab7 in vacuolization, HeLa cells were transfected with a
      series of rab mutants and exposed to VacA. Dominant-negative mutants of rab7
      effectively prevented vacuolization, whereas homologous rab5 and rab9 mutants
      were only partially inhibitory or ineffective, respectively. Expression of wild
      type or GTPase-deficient rab mutants synergized with VacA in inducing
      vacuolization. In vitro fusion of late endosomes was enhanced by active rab7 and
      inhibited by inactive rab7, consistent with vacuole formation by merging of late
      endosomes in a process that requires functional rab7. Taken together, the effects
      of overexpressed rab proteins described here indicate that continuous membrane
      flow along the endocytic pathway is necessary for vacuole growth.

PMID- 9009264
TI  - Differential targeting of closely related ECM glycoproteins: the pherophorin
      family from Volvox.
AB  - The alga Volvox carteri represents one of the simplest multicellular organisms.
      Its extracellular matrix (ECM) is modified under developmental control, e.g.
      under the influence of the sex-inducing pheromone that triggers development of
      males and females at a concentration below 10(-16) M. A novel ECM glycoprotein
      (pherophorin-S) synthesized in response to this pheromone was identified and
      characterized. Although being a typical member of the pherophorins, which are
      identified by a C-terminal domain with sequence homology to the sex-inducing
      pheromone, pherophorin-S exhibits a completely novel set of properties. In
      contrast to the other members of the family, which are found as part of the
      insoluble ECM structures of the cellular zone, pherophorin-S is targeted to the
      cell-free interior of the spherical organism and remains in a soluble state. A
      main structural difference is the presence of a polyhydroxyproline spacer in
      pherophorin-S that is linked to a saccharide containing a phosphodiester bridge
      between two arabinose residues. Sequence comparisons indicate that the self
      assembling proteins that create the main parts of the complex Volvox ECM have
      evolved from a common ancestral gene.

PMID- 9009265
TI  - Ezrin is a cyclic AMP-dependent protein kinase anchoring protein.
AB  - cAMP-dependent protein kinase (A-kinase) anchoring proteins (AKAPs) are
      responsible for the subcellular sequestration of the type II A-kinase.
      Previously, we identified a 78 kDa AKAP which was enriched in gastric parietal
      cells. We have now purified the 78 kDa AKAP to homogeneity from gastric fundic
      mucosal supernates using type II A-kinase regulatory subunit (RII) affinity
      chromatography. The purified 78 kDa AKAP was recognized by monoclonal antibodies
      against ezrin, the canalicular actin-associated protein. Recombinant ezrin
      produced in either Sf9 cells or bacteria also bound RII. Recombinant radixin and
      moesin, ezrin-related proteins, also bound RII in blot overlay. Analysis of
      recombinant truncations of ezrin mapped the RII binding site to a region between
      amino acids 373 and 439. This region contained a 14-amino-acid amphipathic alpha
      helical putative RII binding region. A synthetic peptide containing the
      amphipathic helical region (ezrin409-438) blocked RII binding to ezrin, but a
      peptide with a leucine to proline substitution at amino acid 421 failed to
      inhibit RII binding. In mouse fundic mucosa, RII immunoreactivity redistributed
      from a predominantly cytosolic location in resting parietal cells, to a
      canalicular pattern in mucosa from animals stimulated with gastrin. These results
      demonstrate that ezrin is a major AKAP in gastric parietal cells and may function
      to tether type II A-kinase to a region near the secretory canaliculus.

PMID- 9009266
TI  - The Hansenula polymorpha PEX14 gene encodes a novel peroxisomal membrane protein
      essential for peroxisome biogenesis.
AB  - We have cloned the Hansenula polymorpha PEX14 gene by functional complementation
      of the chemically induced pex14-1 mutant, which lacked normal peroxisomes. The
      sequence of the PEX14 gene predicts a novel protein product (Pex14p) of 39 kDa
      which showed no similarity to any known protein and lacked either of the two
      known peroxisomal targeting signals. Biochemical and electron microscopical
      analysis indicated that Pex14p is a component of the peroxisomal membrane. The
      synthesis of Pex14p is induced by peroxisome-inducing growth conditions. In cells
      of both pex14-1 and a PEX14 disruption mutant, peroxisomal membrane remnants were
      evident; these contained the H.polymorpha peroxisomal membrane protein Pex3p
      together with a small amount of the major peroxisomal matrix proteins alcohol
      oxidase, catalase and dihydroxyacetone synthase, the bulk of which resided in the
      cytosol. Unexpectedly, overproduction of Pex14p in wild-type H. polymorpha cells
      resulted in a peroxisome-deficient phenotype typified by the presence of numerous
      small vesicles which lacked matrix proteins; these were localized in the cytosol.
      Apparently, the stoichiometry of Pex14p relative to one or more other components
      of the peroxisome biogenesis machinery appears to be critical for protein import.

PMID- 9009267
TI  - Cooperation of enzymatic and chaperone functions of trigger factor in the
      catalysis of protein folding.
AB  - The trigger factor of Escherichia coli is a prolyl isomerase and accelerates
      proline-limited steps in protein folding with a very high efficiency. It
      associates with nascent polypeptide chains at the ribosome and is thought to
      catalyse the folding of newly synthesized proteins. In its enzymatic mechanism
      the trigger factor follows the Michaelis-Menten equation. The unusually high
      folding activity of the trigger factor originates from its tight binding to the
      folding protein substrate, as reflected in the low Km value of 0.7 microM. In
      contrast, the catalytic constant kcat is small and shows a value of 1.3 s(-1) at
      15 degrees C. An unfolded protein inhibits the trigger factor in a competitive
      fashion. The isolated catalytic domain of the trigger factor retains the full
      prolyl isomerase activity towards short peptides, but in a protein folding
      reaction its activity is 800-fold reduced and no longer inhibited by an unfolded
      protein. Unlike the prolyl isomerase site, the polypeptide binding site obviously
      extends beyond the FKBP domain. Together, this suggests that the good substrate
      binding, i.e. the chaperone property, of the intact trigger factor is responsible
      for its high efficiency as a catalyst of proline-limited protein folding.

PMID- 9009268
TI  - Hepadnavirus assembly and reverse transcription require a multi-component
      chaperone complex which is incorporated into nucleocapsids.
AB  - Assembly of hepadnaviruses depends on the formation of a ribonucleoprotein (RNP)
      complex comprising the viral polymerase polypeptide and an RNA segment, epsilon,
      present on pregenomic RNA. This interaction, in turn, activates the reverse
      transcription reaction, which is primed by a tyrosine residue on the polymerase.
      We have shown recently that the formation of this RNP complex in an avian
      hepadnavirus, the duck hepatitis B virus, depends on cellular factors that
      include the heat shock protein 90 (Hsp90). We now report that RNP formation also
      requires ATP hydrolysis and the function of p23, a recently identified chaperone
      partner for Hsp90. Furthermore, we also provide evidence that the chaperone
      complex is incorporated into the viral nucleocapsids in a polymerase-dependent
      reaction. Based on these findings, we propose a model for hepadnavirus assembly
      and priming of viral DNA synthesis where a dynamic, energy-driven process,
      mediated by a multi-component chaperone complex consisting of Hsp90, p23 and,
      potentially, additional factors, maintains the reverse transcriptase in a
      specific conformation that is competent for RNA packaging and protein priming of
      viral DNA synthesis.

PMID- 9009269
TI  - A domain of TEL conserved in a subset of ETS proteins defines a specific
      oligomerization interface essential to the mitogenic properties of the TEL-PDGFR
      beta oncoprotein.
AB  - TEL is a novel member of the ETS family of transcriptional regulators which is
      frequently involved in human leukemias as the result of specific chromosomal
      translocations. We show here by co-immunoprecipitation and GST chromatography
      analyses that TEL and TEL-derived fusion proteins form homotypic oligomers in
      vitro and in vivo. Deletion mutagenesis identifies the TEL oligomerization domain
      as a 65 amino acid region which is conserved in a subset of the ETS proteins
      including ETS-1, ETS-2, FLI-1, ERG-2 and GABP alpha in vertebrates and PNTP2, YAN
      and ELG in Drosophila. TEL-induced oligomerization is shown to be essential for
      the constitutive activation of the protein kinase activity and mitogenic
      properties of TEL-platelet derived growth factor receptor beta (PDGFR beta), a
      fusion oncoprotein characteristic of the leukemic cells of chronic myelomonocytic
      leukemia harboring a t(5;12) chromosomal translocation. Swapping experiments in
      which the TEL oligomerization domain was exchanged by the homologous domains of
      representative vertebrate ETS proteins including ETS-1, ERG-2 and GABP alpha show
      that oligomerization is a specific property of the TEL amino-terminal conserved
      domain. These results indicate that the amino-terminal domain conserved in a
      subset of the ETS proteins has evolved to generate a specialized protein-protein
      interaction interface which is likely to be an important determinant of their
      specificity as transcriptional regulators.

PMID- 9009270
TI  - Functional characterization of the Cdc42p binding domain of yeast Ste20p protein
      kinase.
AB  - Ste20p from Saccharomyces cerevisiae belongs to the Ste20p/p65PAK family of
      protein kinases which are highly conserved from yeast to man and regulate
      conserved mitogen-activated protein kinase pathways. Ste20p fulfills multiple
      roles in pheromone signaling, morphological switching and vegetative growth and
      binds Cdc42p, a Rho-like small GTP binding protein required for polarized
      morphogenesis. We have analyzed the functional consequences of mutations that
      prevent binding of Cdc42p to Ste20p. The complete amino-terminal, non-catalytic
      half of Ste20p, including the conserved Cdc42p binding domain, was dispensable
      for heterotrimeric G-protein-mediated pheromone signaling. However, the Cdc42p
      binding domain was necessary for filamentous growth in response to nitrogen
      starvation and for an essential function that Ste20p shares with its isoform
      Cla4p during vegetative growth. Moreover, the Cdc42p binding domain was required
      for cell-cell adhesion during conjugation. Subcellular localization of wild-type
      and mutant Ste20p fused to green fluorescent protein showed that the Cdc42p
      binding domain is needed to direct localization of Ste20p to regions of polarized
      growth. These results suggest that Ste20p is regulated in different developmental
      pathways by different mechanisms which involve heterotrimeric and small GTP
      binding proteins.

PMID- 9009271
TI  - White collar 2, a partner in blue-light signal transduction, controlling
      expression of light-regulated genes in Neurospora crassa.
AB  - A saturating genetic dissection of 'blind' mutants in Neurospora crassa has
      identified a total of two non-redundant loci (wc-1 and wc-2) each of which is
      required for blue-light perception/signal transduction. Previously, we
      demonstrated that WC1 is a putative zinc finger transcription factor able to bind
      specifically to a light-regulated promoter. Here, we present the cloning and
      characterization of the wc-2 gene. We demonstrate using mutation analysis and in
      vitro DNA-binding assays that WC2, the second partner of this light signal
      transduction system, encodes a functional zinc finger DNA-binding protein with
      putative PAS dimerization and transcription activation domains. This molecular
      genetic dissection of the second of two components of this light signal
      transduction system has enabled us to devise a model whereby WC1 and WC2 are
      proposed to interact via homologous PAS domains, bind to promoters of light
      regulated genes and activate transcription. As such, this study provides the
      first insight into two co-operating partners in blue-light signal transduction in
      any organism and describes the molecular tools with which to dissect this
      enigmatic process.

PMID- 9009272
TI  - Identification of intracellular and extracellular domains mediating signal
      transduction in the inhibitory glycine receptor chloride channel.
AB  - Fast synaptic neurotransmission is mediated by transmitter-activated
      conformational changes in ligand-gated ion channel receptors, culminating in
      opening of the integral ion channel pore. Human hereditary hyperekplexia, or
      startle disease, is caused by mutations in both the intracellular or
      extracellular loops flanking the pore-lining M2 domain of the glycine receptor
      alpha1 subunit. These flanking domains are designated the M1-M2 loop and the M2
      M3 loop respectively. We show that four startle disease mutations and six
      additional alanine substitution mutations distributed throughout both loops
      result in uncoupling of the ligand binding sites from the channel activation
      gate. We therefore conclude that the M1-M2 and M2-M3 loops act in parallel to
      activate the channel. Their locations strongly suggest that they act as hinges
      governing allosteric control of the M2 domain. As the members of the ligand-gated
      ion channel superfamily share a common structure, this signal transduction model
      may apply to all members of this superfamily.

PMID- 9009273
TI  - Mouse disabled (mDab1): a Src binding protein implicated in neuronal development.
AB  - Here, we identify a mouse homolog of the Drosophila Disabled (Dab) protein,
      mDab1, and show it is an adaptor molecule functioning in neural development. We
      find that mDab1 is expressed in certain neuronal and hematopoietic cell lines,
      and is localized to the growing nerves of embryonic mice. During mouse
      embryogenesis, mDab1 is tyrosine phosphorylated when the nervous system is
      undergoing dramatic expansion. However, when nerve tracts are established, mDab1
      lacks detectable phosphotyrosine. Tyrosine-phosphorylated mDab1 associates with
      the SH2 domains of Src, Fyn and Abl. An interaction between mDab1 and Src is
      observed when P19 embryonal carcinoma (EC) cells undergo differentiation into
      neuronal cell types. mDab1 can also form complexes with cellular phosphotyrosyl
      proteins through a domain that is related to the phosphotyrosine binding (PTB)
      domains of the Shc family of adaptor proteins. The mDab1 PTB domain binds to
      phosphotyrosine-containing proteins of 200, 120 and 40 kDa from extracts of
      embryonic mouse heads. The properties of mDab1 and genetic analysis of Dab in
      Drosophila suggest that these molecules function in key signal transduction
      pathways involved in the formation of neural networks.

PMID- 9009274
TI  - Bronchial hyperreactivity, increased endotoxin lethality and melanocytic
      tumorigenesis in transgenic mice overexpressing platelet-activating factor
      receptor.
AB  - Although platelet-activating factor (PAF) has been shown to exert pleiotropic
      effects on isolated cells or tissues, controversy still exists as to whether it
      plays significant pathophysiological roles in vivo. To answer this question, we
      established transgenic mice over-expressing a guinea-pig PAF receptor (PAFR). The
      transgenic mice showed a bronchial hyperreactivity to methacholine and an
      increased mortality when exposed to bacterial endotoxin. An aberrant
      melanogenesis and proliferative abnormalities in the skin were also observed in
      the transgenic mice, some of which spontaneously bore melanocytic tumors in the
      dermis after aging. Thus, PAFR transgenic mice proved to be a useful model for
      studying the basic pathophysiology of bronchial asthma and endotoxin-induced
      death, and screening of therapeutics for these disorders. Furthermore, our
      findings provide new insights regarding the role of PAF in the morphogenesis of
      dermal tissues as well as the mitogenic activity of PAF and PAFR in vivo.

PMID- 9009275
TI  - Cyclosporin A-sensitive induction of the Epstein-Barr virus lytic switch is
      mediated via a novel pathway involving a MEF2 family member.
AB  - Induction of the Epstein-Barr virus (EBV) lytic cycle by crosslinking surface
      immunoglobulin is inhibited by the immunosuppressants cyclosporin A (CsA) and
      FK506. This correlates with the ability of CsA to inhibit Ca2+-dependent
      transcription of the lytic cycle switch gene BZLF1. It is shown here that CsA
      sensitivity maps to three sites (ZIA, ZIB and ZID) that bind the serum response
      factor-related protein MEF2D. A synthetic promoter containing multiple copies of
      a MEF2D site from Zp, in conjunction with a CREB/AP-1 site (ZII) from Zp,
      exhibits CsA-sensitive inducibility. Furthermore, the Zp MEF2D sites were
      functionally interchangeable with MEF2 sites derived from heterologous promoters.
      While no evidence of a NFAT family member binding to either the MEF2 or CREB/AP-1
      sites was obtained, it could be demonstrated that CsA-sensitive induction of Zp
      was mediated by calcineurin and NFATc2 in synergy with either phorbol ester or
      especially with the EBV-induced Ca2+/calmodulin-dependent kinase type IV/Gr.
      These studies identify Zp as prototypic of a novel class of CsA-sensitive and
      NFAT-dependent promoters defined by the presence of MEF2 sites.

PMID- 9009276
TI  - Molecular anatomy of a transcription activation patch: FIS-RNA polymerase
      interactions at the Escherichia coli rrnB P1 promoter.
AB  - FIS, a site-specific DNA binding and bending protein, is a global regulator of
      gene expression in Escherichia coli. The ribosomal RNA promoter rrnB P1 is
      activated 3- to 7-fold in vivo by a FIS dimer that binds a DNA site immediately
      upstream of the DNA binding site for the C-terminal domain (CTD) of the alpha
      subunit of RNA polymerase (RNAP). In this report, we identify several FIS side
      chains important specifically for activation of transcription at rrnB P1. These
      side chains map to positions 68, 71 and 74, in and flanking a surface-exposed
      loop adjacent to the helix-turn-helix DNA binding motif of the protein. We also
      present evidence suggesting that FIS activates transcription at rrnB P1 by
      interacting with the RNAP alphaCTD. Our results suggest a model for FIS-mediated
      activation of transcription at rrnB P1 that involves interactions between FIS and
      the RNAP alphaCTD near the DNA surface. Although FIS and the transcription
      activator protein CAP have little structural similarity, they both bend DNA, use
      a similarly disposed activation loop and target the same region of the RNAP
      alphaCTD, suggesting that this is a common architecture at bacterial promoters.

PMID- 9009277
TI  - Identification of a transcript release activity acting on ternary transcription
      complexes containing murine RNA polymerase I.
AB  - Termination of mammalian ribosomal gene transcription by RNA polymerase I (Pol I)
      requires binding of the nucleolar factor TTF-I (transcription termination factor
      for Pol I) to specific rDNA terminator elements. We have used recombinant murine
      TTF-I in an immobilized tailed template assay to analyze individual steps of the
      termination reaction. We demonstrate that, besides the TTF-I-DNA complex which
      stops elongating Pol I, an additional activity is required to release both the
      nascent transcript and Pol I from the template. Moreover, transcript release, but
      not TTF-I-directed pausing, depends on upstream sequences directly flanking the
      terminator element. Together, complete termination of Pol I transcription
      requires TTF-I bound to the terminator DNA, a stretch of thymidine residues
      upstream of the TTF-I-mediated pause site and an activity which releases the RNA
      transcript and Pol I from the DNA template.

PMID- 9009278
TI  - Staf, a promiscuous activator for enhanced transcription by RNA polymerases II
      and III.
AB  - Staf is a zinc finger protein that we recently identified as the transcriptional
      activator of the RNA polymerase III-transcribed selenocysteine tRNA gene. In this
      work we demonstrate that enhanced transcription of the majority of vertebrate
      snRNA and snRNA-type genes, transcribed by RNA polymerases II and III, also
      requires Staf. DNA binding assays and microinjection of mutant genes into Xenopus
      oocytes showed the presence of Staf-responsive elements in the genes for human
      U4C, U6, Y4 and 7SK, Xenopus U1b1, U2, U5 and MRP and mouse U6 RNAs. Using
      recombinant Staf, we established that it mediates the activating properties of
      Staf-responsive elements on RNA polymerase II and III snRNA promoters in vivo.
      Lastly a 19 bp consensus sequence for the Staf binding site,
      YY(A/T)CCC(A/G)N(A/C)AT(G/C)C(A/C)YY-RCR, was derived by binding site selection.
      It enabled us to identify 23 other snRNA and snRNA-type genes carrying potential
      Staf binding sites. Altogether, our results emphasize the prime importance of
      Staf as a novel activator for enhanced transcription of snRNA and snRNA-type
      genes.

PMID- 9009279
TI  - The G2/M DNA damage checkpoint inhibits mitosis through Tyr15 phosphorylation of
      p34cdc2 in Aspergillus nidulans.
AB  - It is possible to cause G2 arrest in Aspergillus nidulans by inactivating either
      p34cdc2 or NIMA. We therefore investigated the negative control of these two
      mitosis-promoting kinases after DNA damage. DNA damage caused rapid Tyr15
      phosphorylation of p34cdc2 and transient cell cycle arrest but had little effect
      on the activity of NIMA. Dividing cells deficient in Tyr15 phosphorylation of
      p34cdc2 were sensitive to both MMS and UV irradiation and entered lethal
      premature mitosis with damaged DNA. However, non-dividing quiescent conidiospores
      of the Tyr15 mutant strain were not sensitive to DNA damage. The UV and MMS
      sensitivity of cells unable to tyrosine phosphorylate p34cdc2 is therefore caused
      by defects in DNA damage checkpoint regulation over mitosis. Both the nimA5 and
      nimT23 temperature-sensitive mutations cause an arrest in G2 at 42 degrees C.
      Addition of MMS to nimT23 G2-arrested cells caused a marked delay in their entry
      into mitosis upon downshift to 32 degrees C and this delay was correlated with a
      long delay in the dephosphorylation and activation of p34cdc2. Addition of MMS to
      nimA5 G2-arrested cells caused inactivation of the H1 kinase activity of p34cdc2
      due to an increase in its Tyr15 phosphorylation level and delayed entry into
      mitosis upon return to 32 degrees C. However, if Tyr15 phosphorylation of p34cdc2
      was prevented then its H1 kinase activity was not inactivated upon MMS addition
      to nimA5 G2-arrested cells and they rapidly progressed into a lethal mitosis upon
      release to 32 degrees C. Thus, Tyr15 phosphorylation of p34cdc2 in G2 arrests
      initiation of mitosis after DNA damage in A. nidulans.

PMID- 9009280
TI  - Meiotic nuclear reorganization: switching the position of centromeres and
      telomeres in the fission yeast Schizosaccharomyces pombe.
AB  - In fission yeast meiotic prophase, telomeres are clustered near the spindle pole
      body (SPB; a centrosome-equivalent structure in fungi) and take the leading
      position in chromosome movement, while centromeres are separated from the SPB.
      This telomere position contrasts with mitotic nuclear organization, in which
      centromeres remain clustered near the SPB and lead chromosome movement. Thus,
      nuclear reorganization switching the position of centromeres and telomeres must
      take place upon entering meiosis. In this report, we analyze the nuclear location
      of centromeres and telomeres in genetically well-characterized meiotic mutant
      strains. An intermediate structure for telomere-centromere switching was observed
      in haploid cells induced to undergo meiosis by synthetic mating pheromone;
      fluorescence in situ hybridization revealed that in these cells, both telomeres
      and centromeres were clustered near the SPB. Further analyses in a series of
      mutants showed that telomere-centromere switching takes place in two steps;
      first, association of telomeres with the SPB and, second, dissociation of
      centromeres from the SPB. The first step can take place in the haploid state in
      response to mating pheromone, but the second step does not take place in haploid
      cells and probably depends on conjugation-related events. In addition, a linear
      minichromosome was also co-localized with authentic telomeres instead of
      centromeres, suggesting that telomere clustering plays a role in organizing
      chromosomes within a meiotic prophase nucleus.

PMID- 9009281
TI  - ATP-dependent resolution of R-loops at the ColE1 replication origin by
      Escherichia coli RecG protein, a Holliday junction-specific helicase.
AB  - The RecG protein of Escherichia coli is a DNA helicase that promotes branch
      migration of the Holliday junctions. We found that overproduction of RecG protein
      drastically decreased copy numbers of ColE1-type plasmids, which require R-loop
      formation between the template DNA and a primer RNA transcript (RNA II) for the
      initiation of replication. RecG efficiently inhibited in vitro ColE1 DNA
      synthesis in a reconstituted system containing RNA polymerase, RNase HI and DNA
      polymerase I. RecG promoted dissociation of RNA II from the R-loop in a manner
      that required ATP hydrolysis. These results suggest that overproduced RecG
      inhibits the initiation of replication by prematurely resolving the R-loops
      formed at the replication origin region of these plasmids with its unique
      helicase activity. The possibility that RecG regulates the initiation of a unique
      mode of DNA replication, oriC-independent constitutive stable DNA replication, by
      its activity in resolving R-loops is discussed.

PMID- 9009282
TI  - Identification of the gene family encoding the 160-kilodalton Trypanosoma cruzi
      complement regulatory protein.
AB  - Trypanosoma cruzi trypomastigotes are exquisitely resistant to the lytic effects
      of vertebrate complement, and this characteristic contributes to the survival of
      the parasites in the host bloodstream. Trypomastigotes avoid complement-mediated
      lysis by the production of a surface glycoprotein that inhibits the formation of
      the alternative and classical C3 convertase, thus preventing activation and
      amplification of the complement cascade at the parasite surface. We have
      developed a monoclonal antibody to the 160-kDa T. cruzi complement regulatory
      protein (CRP) and describe a one-step immunoaffinity purification procedure. The
      CRP was purified to homogeneity and subjected to amino-terminal peptide sequence
      analysis. Based on the protein sequence obtained, the CRP was identified as a
      member of a large family of trypomastigote-specific genes, and a complete cDNA
      was isolated and sequenced. The complete coding sequence was cloned in
      Escherichia coli, and antibodies raised against the full-length recombinant
      protein reacted specifically with a 160-kDa protein in trypomastigote membrane
      protein preparations as well as with native, purified CRP. Indirect
      immunofluorescence revealed that the protein is uniformly expressed at the cell
      surfaces of trypomastigotes.

PMID- 9009283
TI  - Antibody- and cell-mediated immune responses of Actinobacillus pleuropneumoniae
      infected and bacterin-vaccinated pigs.
AB  - Current porcine pleuropneumonia bacterins afford only partial protection by
      decreasing mortality but not morbidity. In order to better understand the type(s)
      of immune response associated with protection, antibody- and cell-mediated immune
      responses (CMIR) were compared for piglets before and after administration of a
      commercial bacterin, which confers partial protection, or a low-dose (10(5)
      CFU/ml) aerosol challenge with Actinobacillus pleuropneumoniae CM5 (LD), which
      induces complete protection. Control groups received phosphate-buffered saline or
      adjuvant. Serum antibody response, antibody avidity, delayed-type
      hypersensitivity (DTH), and lymphocyte blastogenic responses were measured and
      compared among treatment groups to the lipopolysaccharide (LPS), capsular
      polysaccharide (CPS), hemolysin (HLY), and outer membrane proteins (OMP) of A.
      pleuropneumoniae. Peripheral blood lymphocytes and sera were collected prior to
      and following primary and secondary immunization-infection and high-dose A.
      pleuropneumoniae CM5 (10(7) CFU/ml) aerosol challenge. Serum antibody and DTH,
      particularly that to HLY, differed significantly between treatment groups, and
      increases were associated with protection. LD-infected piglets had higher
      antibody responses (P < or = 0.01) and antibody avidity (P < or = 0.10) than
      bacterin-vaccinated and control groups. Anti-HLY antibodies were consistently
      associated with protection, whereas anti-LPS and anti-CPS antibodies were not. LD
      infected animals had higher DTH responses, particularly to HLY, than bacterin
      vaccinated pigs (P < or = 0.03). The LD-infected group maintained consistent
      blastogenic responses to HLY, LPS, CPS, and OMP over the course of infection,
      unlike the bacterin-vaccinated and control animals. These data suggest that the
      immune responses induced by a commercial bacterin are very different from those
      induced by LD aerosol infection and that current bacterins may be modified, for
      instance, by addition of HLY, so as to stimulate responses which better reflect
      those induced by LD infection.

PMID- 9009284
TI  - Intravenous immunoglobulin inhibits staphylococcal toxin-induced human
      mononuclear phagocyte tumor necrosis factor alpha production.
AB  - Intravenous gamma immunoglobulin (IVIG) is used as therapy in superantigen
      mediated disease, yet its mode of action is not clear. Pooled immunoglobulin G
      contains high concentrations of staphylococcal exotoxin (SE)-specific antibodies
      which inhibit the in vitro activation of T cells. However, SE and streptococcal
      exotoxins are potent stimulators of monocytes as well. Monocytes exposed to SE in
      vitro release large amounts of tumor necrosis factor alpha (TNF-alpha). The
      purpose of the present study was to determine if SE-specific antibodies in IVIG
      can inhibit the activation of monocytes by SE. We examined the in vitro effect of
      IVIG on the ability of staphylococcal exotoxin A (SEA) and staphylococcal
      exotoxin B (SEB) to stimulate release of TNF-alpha from human mononuclear
      phagocytes (MO). Pretreatment of SEA with 0.1 mg of IVIG per ml resulted in a
      slight decrease of SEA-induced TNF-alpha secretion by MO. In contrast,
      pretreatment of SEB with 0.1 mg of IVIG per ml resulted in significant (greater
      than 50%) inhibition of SEB-induced TNF-alpha secretion at 24, 48, 72, and 96 h
      (P < 0.05 for TNF-alpha levels induced by SEB alone versus SEB pretreated with
      IVIG at all time points). Enzyme-linked immunosorbent assay and Western
      immunoblotting assays of the IVIG revealed high concentrations of antibodies
      against SEB and lower concentrations of antibodies to SEA. These data indicate
      that IVIG can act in a toxin-specific manner to decrease the MO TNF-alpha
      response to superantigens. Such inhibition may be one mechanism by which IVIG
      exerts an immunoregulatory role in superantigen-mediated disease.

PMID- 9009285
TI  - Role of gamma interferon in the host immune and inflammatory responses to
      Pneumocystis carinii infection.
AB  - The role of gamma interferon (IFN-gamma) in host defense to Pneumocystis carinii
      was investigated by use of three different murine models of infection. C57BL/6
      scid/scid (severe combined immunodeficient [SCID]) mice were given intratracheal
      inoculations of P. carinii and reconstituted with splenocytes from either mice
      with disrupted IFN-gamma genes (IFN-gamma-/- mice) or homozygous wild-type (IFN
      gamma+/+) mice. Unreconstituted SCID mice had log10 7.08 +/- 0.13 P. carinii
      nuclei in their lungs at day 22 postinfection, whereas SCID mice reconstituted
      with splenocytes from either wild-type or IFN-gamma-/- mice had cleared the
      infection. However, there was a prolonged and exacerbated inflammatory response
      in the lungs of SCID mice reconstituted with IFN-gamma-/- splenocytes which was
      characterized by interstitial pneumonia, eosinophilia, and multinucleated giant
      cell formation. Similar results were found in C.B17 SCID mice reconstituted with
      CD4+ cells from P. carinii-immunized donors treated with neutralizing anti-IFN
      gamma monoclonal antibody (MAb). These mice resolved their P. carinii infections;
      however, they also exhibited exacerbated lung pathology compared with mice
      treated with a control MAb. Finally, IFN-gamma-/- mice challenged intratracheally
      with P. carinii resolved their infection within 56 days as did IFN-gamma+/- mice.
      Furthermore, depletion of T cells in vivo with a MAb resulted in IFN-gamma-/-
      mice becoming susceptible to P. carinii infection. Together, these data indicate
      that IFN-gamma is not required for resolution of P. carinii infection; however,
      in the absence of IFN-gamma, there is a prolonged and exacerbated P. carinii
      driven interstitial pneumonia characterized by eosinophilia and formation of
      multinucleated giant cells.

PMID- 9009286
TI  - Nramp1 transfection transfers Ity/Lsh/Bcg-related pleiotropic effects on
      macrophage activation: influence on antigen processing and presentation.
AB  - The natural resistance-associated macrophage protein (Nramp1) regulates
      macrophage activation. One of its pleiotropic effects on macrophage function is
      to regulate expression of major histocompatibility class II molecules. In this
      study macrophages stably transfected with the wild-type (infection-resistant) or
      the natural mutant (infection-susceptible) allele of the Nramp1 gene were used to
      study class II expression and processing and presentation of recombinant protein
      antigens to CD4+ T-cell hybridomas. As demonstrated previously for macrophages
      from Nramp1-resistant and -susceptible congenic mouse strains, transfected
      macrophage clones carrying the wild-type allele showed enhanced upregulation of
      class II molecules in response to gamma interferon compared to that shown by
      macrophage clones carrying an endogenous mutant allele or transfected with the
      mutant allele expressed under a viral long terminal repeat promoter. The wild
      type allele-transfected macrophage clones also demonstrated an enhanced,
      lipopolysaccharide-dependent ability to process the recombinant leishmanial
      antigen LACK-delta 1 (the Leishmania homolog of receptors for activated C kinase)
      for presentation to LACK-specific CD4+ T cells. An influence on antigen
      processing must therefore be added to the growing list of pleiotropic effects of
      the Nramp1 gene potentially contributing to its role in infectious and autoimmune
      disease susceptibility. These results also have important implications for
      analysis of T-cell responses to vaccination, especially where antigens are
      presented to the immune system using live Salmonella species or Mycobacterium
      bovis BCG as a vaccine vehicle.

PMID- 9009287
TI  - Analysis of culture filtrate and cell wall-associated antigens of Mycobacterium
      paratuberculosis with monoclonal antibodies.
AB  - Proteins secreted by Mycobacterium species have been suggested as major immune
      targets in the early phase of infection. In this study, we sought to identify
      specific antigens in culture filtrates and in soluble cell extracts of
      Mycobacterium paratuberculosis. The release of antigens into the culture medium
      during growth of the bacilli and the distribution of specific epitopes within the
      Mycobacterium species were investigated by immunoblot analysis with monoclonal
      antibodies (MAbs) raised against M. paratuberculosis antigens. MAb B6A interacted
      with a cellular antigen with an apparent molecular mass of 34.5 kDa in lysates of
      M. paratuberculosis. MAb B6A did not interact with lysates from any other
      mycobacterial species, suggesting recognition of an M. paratuberculosis species
      specific epitope. MAb FL1-A1 reacted with an antigen of 44.3 kDa in M.
      paratuberculosis and a 9-kDa antigen in Mycobacterium kansasii. MAb PII-B1
      reacted with concanavalin A (ConA)-binding cellular and filtrate molecules of M.
      paratuberculosis and with lysates of Mycobacterium kansasii and Mycobacterium
      avium 18. The affinity-purified glycosylated antigens migrated as a diffuse band
      of between 35 and 45.6 kDa and reacted strongly with ovine and bovine
      paratuberculosis serum and polyclonal serum against M. tuberculosis
      lipoarabinomannan antigens. These glycoconjugates were the earliest antigens
      detected in culture filtrates of M. paratuberculosis. Deglycosylation of the ConA
      binding molecules with alpha-mannosidase enzyme abolished the reaction with MAb
      PII-B1 and with bovine but not ovine paratuberculosis serum, suggesting selective
      immunogenicity in the different animal species.

PMID- 9009288
TI  - Salmonella typhi stimulation of human intestinal epithelial cells induces
      secretion of epithelial cell-derived interleukin-6.
AB  - Interleukin 6 (IL-6) is a multifunctional cytokine that has been shown to be
      associated with both systemic and tissue-specific responses within the host.
      Moreover, IL-6 is produced by both lymphoid and nonlymphoid cells and has been
      identified as a growth-inducing, growth-inhibiting, and differentiation-inducing
      factor for these cells. Recent studies of uropathogenic and upper respiratory
      pathogens have suggested that epithelial cell-derived IL-6 plays a role in
      mucosal host-parasite interactions. Since many mucosal enteric pathogens enter
      the host through the epithelial cells of the distal small intestine, a role for
      intestinal epithelial cell-derived IL-6 in the initial interaction between
      bacteria and host might also be predicted. However, no studies to date have
      determined whether the interaction of any bacteria with the epithelial cells that
      line the small intestine of the host can induce IL-6. To address this issue, we
      have established an in vitro model to evaluate the capacity of the gram-negative
      bacterium Salmonella typhi to induce IL-6 in the small intestine epithelial cell
      line Int407 and in other intestinal epithelial cell lines. The results
      demonstrate that both wild-type and live, attenuated S. typhi vaccine strains
      induce small and large intestine epithelial cells to secrete IL-6, and kinetic
      analysis suggests that IL-6 may be one of the earliest responses following
      adherence and invasion of enteric organisms. Thus, these studies suggest a
      physiologic role for epithelial cell-derived IL-6 in the initial interactions
      between host and bacterium in the small intestine.

PMID- 9009289
TI  - Identification of extracellular phospholipase B, lysophospholipase, and
      acyltransferase produced by Cryptococcus neoformans.
AB  - We recently identified phospholipase activity as a potential virulence factor of
      Cryptococcus neoformans. We have now defined the nature of the phospholipase
      activity produced by a clinical isolate of C. neoformans var. neoformans, under
      native conditions, by 1H and 31P nuclear magnetic resonance (NMR) spectroscopy
      and thin-layer chromatography (TLC) of radiolabelled substrates.
      Glycerophosphocholine was identified by NMR spectroscopy as the sole phospholipid
      degradation product of the reaction between substrate phosphatidylcholine (PC)
      and cryptococcal culture supernatants indicating the presence of phospholipase B
      (PLB). No lysophosphatidylcholine (lyso-PC) or products indicative of
      phospholipase C, phospholipase D, or other lipase activity were identified. Use
      of PC and lyso-PC containing radiolabelled acyl chains and separation of products
      by TLC confirmed the PLB and lysophospholipase (LPL) activities.
      Lysophospholipase transacylase (LPTA) activity was identified by the formation of
      radioactive PC from lyso-PC. Extracellular enzyme production was maximal after 6
      to 10 h in fresh medium. Assay conditions were optimized for pH, linearity with
      time, enzyme concentration, and saturation by substrates to allow comparison with
      phospholipases from other organisms. LPL activity was 10- to 20-fold greater than
      PLB activity, with mean (+/- standard deviation) specific activities of 34.9 +/-
      7.9 and 3.18 +/- 0.2 micromol of substrate hydrolyzed per min per mg of protein,
      respectively. The response of PLB to increasing substrate concentrations was
      bimodal, whereas inhibition of LPL and LPTA activities occurred at concentrations
      of substrate lyso-PC greater than 200 microM. Enzyme activities were stable at
      acid pH (3.8), with pH optima of 3.5 to 4.5. Activities were unchanged in the
      presence of exogenous serine protease inhibitors, divalent cations, and EDTA. We
      conclude that C. neoformans produces highly active extracellular PLB, LPL, and
      LPTA under native conditions.

PMID- 9009291
TI  - Role of the carboxyl-terminal region of Porphyromonas gingivalis fimbrillin in
      binding to salivary proteins.
AB  - Porphyromonas gingivalis fimbriae are considered to play an important role in the
      adherence and colonization of the bacteria in the oral cavity. In this study, we
      generated and purified three carboxyl-terminal variants of recombinant fimbrillin
      (r-FimA 224-337, r-FimA 266-337, and r-FimA 287-337, corresponding to amino acid
      residues 224 to 337, 266 to 337, and 287 to 337, respectively, of the 43-kDa
      fimbrillin of P. gingivalis 2561). They were used as inhibitors of P. gingivalis
      cell binding to human salivary protein-coated hydroxyapatite (HAP) beads. All of
      the carboxyl-terminal region polypeptides inhibited binding in a dose-dependent
      manner; however, the inhibitory effect of r-FimA 287-337 was less than that of
      the other two polypeptides when HAP beads were coated with whole saliva or
      purified salivary proline-rich protein 1 (PRP1). Assays of binding of a synthetic
      peptide corresponding to amino acid residues 266 to 286 of P. gingivalis 2561
      fimbrillin to salivary proteins showed that this peptide bound strongly to whole
      saliva or PRP1 but only weakly to statherin. These results suggest that the
      carboxyl-terminal region corresponding to amino acid residues 266 to 337 of P.
      gingivalis fimbrillin plays an important role in binding to salivary proteins and
      that the domain corresponding to amino acids 266 to 286 is likely a major binding
      site for PRP1s and the domain corresponding to amino acids 287 to 337 is likely a
      major binding site for statherin.

PMID- 9009290
TI  - Molecular characterization of a 6.6-kilodalton Borrelia burgdorferi outer
      membrane-associated lipoprotein (lp6.6) which appears to be downregulated during
      mammalian infection.
AB  - Isolated outer membranes of Borrelia burgdorferi 297 were utilized to obtain
      partial amino acid sequence information for a low-molecular-weight, outer
      membrane-associated polypeptide. Degenerate oligonucleotide primers based upon
      this information were used to amplify a 100-bp probe for detection of the
      corresponding full-length gene within a B. burgdorferi total genomic library. The
      relevant open reading frame (ORF) encoded a polypeptide comprised of a 17-amino
      acid putative signal peptide terminated by LFVAC, a probable consensus sequence
      for lipoprotein modification, and a mature protein of 51 amino acids (predicted
      molecular mass of 5.8 kDa). The DNA sequences of the corresponding ORFs in B.
      burgdorferi 297 and B31 were identical; the corresponding ORF in strain N40
      differed by only one nucleotide. Assuming conventional processing and acylation,
      the molecular weight of the lipoprotein, designated lp6.6, is about 6,600. The
      lp6.6 gene, which was localized to the 49-kb linear plasmid of B. burgdorferi,
      subsequently was cloned and expressed in Escherichia coli as a fusion protein
      with glutathione S-transferase. Immunoblot analysis with monoclonal antibody
      240.7 revealed that lp6.6 was identical to a low-molecular-weight, highly
      conserved B. burgdorferi lipoprotein reported previously (L. I. Katona, G. Beck,
      and G. S. Habicht, Infect. Immun. 60:4995-5003, 1992). Results of indirect
      immunofluorescence assays, growth inhibition assays, passive immunizations, and
      active immunizations indicated that this outer membrane-associated antigen is not
      surface exposed in B. burgdorferi. Particularly interesting was the finding that
      mice and rhesus monkeys chronically infected with B. burgdorferi failed to
      develop antibodies against this antigen. We propose that high-level expression of
      lp6.6 is associated with the arthropod phase of the spirochetal life cycle and
      that expression of the gene is downregulated during mammalian infection.

PMID- 9009292
TI  - Examination of diarrheagenicity of cytolethal distending toxin: suckling mouse
      response to the products of the cdtABC genes of Shigella dysenteriae.
AB  - Some strains of Escherichia coli, Shigella spp., and Campylobacter spp. that have
      been implicated in diarrheal disease produce cytolethal distending toxin (CDT).
      CDT induces unique morphological changes in Chinese hamster ovary cells, but its
      association with diarrheal disease is unclear. We studied the diarrheagenicity of
      CDT using the cdt genes that we originally cloned from Shigella dysenteriae. The
      cdt genes were subcloned into a high-copy-number plasmid in E. coli JM109 to
      achieve high-level CDT production into the culture supernatant. An isogenic CDT-
      derivative was constructed by deletion of the 0.9-kb sequence internal to the cdt
      genes. A suckling mouse model was established, in which the intragastrically
      administered culture supernatant of the CDT+ E. coli strain induced excretion of
      loose and/or watery feces more often than did that of the CDT- strain in 24 h.
      The partially purified CDT preparation induced profuse watery diarrhea by 12 h in
      this model. High-level intestinal fluid accumulation in 4 h appeared to be
      related to the watery diarrhea. The results indicate that CDT is diarrheagenic to
      suckling mice and suggest that diarrheagenicity is dependent on CDT level. The
      preparations containing wild-type CDT induced tissue damage (necrosis and
      reparative hyperplasia) in the descending colon, whereas the tissues of the small
      intestines remained apparently intact. Association between the colonic damage and
      diarrhea is unclear and needs further investigation.

PMID- 9009293
TI  - Ferric iron reduction by Cryptococcus neoformans.
AB  - The pathogenic yeast Cryptococcus neoformans must reduce Fe(III) to Fe(II) prior
      to uptake. We investigated mechanisms of reduction using the chromogenic ferrous
      chelator bathophenanthroline disulfonate. Iron-depleted cells reduced 57 nmol of
      Fe(III) per 10(6) cells per h, while iron-replete cells reduced only 8 nmol of
      Fe(III). Exponential-phase cells reduced the most and stationary-phase cells
      reduced the least Fe(III), independent of iron status. Supernatants from iron
      depleted cells reduced up to 2 nmol of Fe(III) per 10(6) cells per h, while
      supernatants from iron-replete cells reduced 0.5 nmol of Fe(III), implying
      regulation of the secreted reductant(s). One such reductant is 3
      hydroxyanthranilic acid (3HAA), which was found at concentrations up to 29 microM
      in iron-depleted cultures but <2 microM in cultures supplemented with iron.
      Moreover, when washed and resuspended in low iron medium, iron-depleted cells
      secreted 20.4 microM 3HAA, while iron-replete cells secreted only 4.5 microM
      3HAA. Each mole of 3HAA reduced 3 mol of Fe(III), and increasing 3HAA
      concentrations correlated with increasing reducing activity of supernatants;
      however, 3HAA accounted for only half of the supernatant's reducing activity,
      indicating the presence of additional reductants. Finally, we found that
      melanized stationary-phase cells reduced 2 nmol of Fe(III) per 10(6) cells per h-
      16 times the rate of nonmelanized cells--suggesting that this redox polymer
      participates in reduction of Fe(III).

PMID- 9009294
TI  - Pathogenesis of Acanthamoeba keratitis: carbohydrate-mediated host-parasite
      interactions.
AB  - Acanthamoeba keratitis is a sight-threatening corneal infection. In a recent
      study, the saccharide mannose has been shown to inhibit the binding of
      Acanthamoeba organisms to the epithelium of the cornea (L. D. Morton, G. L.
      McLaughlin, and H. E. Whiteley, Infect. Immun. 59:3819-3822, 1991). In an attempt
      to determine the molecular mechanism by which acanthamoebae adhere to the surface
      of the cornea, the present study was designed to determine whether Acanthamoeba
      castellanii derived from an infected human cornea (i) binds to mannose-containing
      glycoproteins (mannose-GPs) of corneal epithelium and (ii) expresses one or more
      mannose-binding proteins. Mannose-GPs of primary cell cultures of rabbit corneal
      epithelium were isolated by using three different agarose-conjugated, mannose
      specific lectins. By electrophoresis blot-overlay assays, 35S-labeled
      acanthamoebae were shown to bind to mannose-GPs of corneal epithelium and to a
      neoglycoprotein, mannose-bovine serum albumin (mannose-BSA). 35S-labeled
      acanthamoebae also bound to microtiter wells coated with mannose-BSA in a
      concentration-dependent manner. The binding of amoebae to mannose-GPs was blocked
      by free methyl-alpha-D-mannopyranoside. The parasites did not bind to galactose
      BSA or to many other proteins lacking mannose residues. A membrane-associated
      mannose-binding protein (136 kDa) of A. castellanii was isolated by affinity
      chromatography of detergent extracts of unlabeled parasites and of cell surface
      biotin-labeled parasites on a p-aminophenyl alpha-D-mannopyranoside-agarose
      column. The affinity-purified protein of the amoeba was shown to bind
      specifically to mannose-BSA. In summary, a mannose-binding protein is present on
      the surface membranes of Acanthamoeba, and corneal epithelial cells express
      Acanthamoeba-reactive GPs. One of the mechanisms of Acanthamoeba adhesion to the
      corneal surface may involve interactions between the mannose-binding protein of
      Acanthamoeba and mannose-GPs on the surface of corneal epithelium.

PMID- 9009295
TI  - Passive immunity to infection with Yersinia spp. mediated by anti-recombinant V
      antigen is dependent on polymorphism of V antigen.
AB  - The V antigen is a 37-kDa secreted polypeptide encoded on the 70-kb virulence
      plasmid of pathogenic Yersinia spp. Besides having regulatory functions, it is
      known to be a virulence factor and a protective antigen. DNA sequencing of the
      most common serotypes of human pathogenic Yersinia enterocolitica and Y.
      pseudotuberculosis revealed that two evolutionary distinct types of V antigen
      exist in Yersinia spp. One type is represented by Y. enterocolitica serotype 08
      strains WA, WA-314, and NCTC 10938 (designated LcrV-YenO8); the other type
      comprises Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica serotypes O3,
      O9, and O5,27 (LcrV-Yps). A hypervariable region between amino acids 225 and 232
      represents the main difference between the two types. By raising monospecific
      antisera against both types of V antigen (anti-rVO8 and anti-rVO3), we were able
      to demonstrate that, in general, passive immunization of mice against a challenge
      with yersiniae was possible with both anti-Y. enterocolitica V antigen sera.
      However, anti-V antigen serum was protective only if the immunizing V antigen was
      the same type as the V antigen produced by the infective strain. The failure of
      the American V antigen type represented by Y. enterocolitica serotype O8 to
      protect against Yersinia spp. carrying the other V antigen type (LcrV-Yps) could
      be an explanation for the presence of plague foci in American countries.

PMID- 9009296
TI  - Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and
      aroC aroD and immune response in humans.
AB  - A single-dose, oral Salmonella typhi vaccine strain has been sought as a carrier
      or vector of cloned genes encoding protective antigens of other pathogens. Such a
      hybrid vaccine, administered orally, would stimulate immune responses both at the
      mucosal surface and in the systemic compartment and would potentially provide
      protection against multiple pathogens. S. typhi CVD 908 and CVD 906, which harbor
      deletions in aroC and aroD, were further engineered by deletion in htrA to
      produce strains CVD 908-htrA and CVD 906-htrA, which are unable to sustain growth
      and are severely impaired in their ability to survive in host tissues. These
      strains were fed to humans at doses of 5 x 10(7) to 5 x 10(9) CFU with buffer,
      and safety and immune responses were assessed. CVD 908-htrA and CVD 906-htrA were
      well tolerated in volunteers; mild diarrhea in 3 of 36 volunteers and mild fever
      in 1 volunteer were the only notable adverse responses. The vaccine strains were
      not detected in blood cultures and only transiently detected in stool. Serum
      immune responses to S. typhi lipopolysaccharide and H antigens were observed in
      75 to 100% of volunteers who received 5 x 10(8) to 5 x 10(9) CFU, and cells
      secreting S. typhi-specific antibodies were found in all volunteers after
      ingestion of either strain. Sixty-three percent to 83% of volunteers developed
      lymphoproliferative responses to S. typhi flagellar and particulate antigens
      after the higher doses. These studies demonstrate the potential of CVD 908-htrA
      as a live vector for the delivery of heterologous genes, and a clinical trial of
      such a construct is planned.

PMID- 9009297
TI  - Evidence for a protective role of tumor necrosis factor in the acute phase of
      Trypanosoma cruzi infection in mice.
AB  - A possible role for tumor necrosis factor (TNF) alpha during Trypanosoma cruzi
      infection was explored by using transgenic mice expressing in blood high levels
      of a soluble TNFR1-FcIgG3 fusion protein, which neutralizes the effects of TNF in
      vivo. Nontransgenic littermates were used as controls. The transgenic mice showed
      high susceptibility to T. cruzi infection. Inocula sublethal for control mice
      resulted in over 80% mortality associated with higher levels of parasites in the
      blood. In histological sections of the hearts of transgenic mice, large parasitic
      clusters without inflammatory cell infiltrates around the parasites were seen,
      while smaller parasitic clusters associated with leukocytes were seen in control
      mice. No difference in specific antibody response or lymphocyte composition of
      the spleen was found between transgenic and control mice, although the
      unresponsiveness of spleen cells to concanavalin A stimulation in vitro, typical
      of the acute phase of T. cruzi infection, was less pronounced in transgenic mice.
      Infected transgenic mice produced higher levels of gamma interferon than did
      control mice. These results confirm that TNF is involved in mechanisms leading to
      parasite clearance and protection from death in the acute phase of T. cruzi
      infection. More importantly, the data reveal that TNF is necessary for the
      establishment of effective tissue inflammation and parasite load control in acute
      experimental Chagas' disease myocarditis.

PMID- 9009298
TI  - Role of coagulase in a murine model of hematogenous pulmonary infection induced
      by intravenous injection of Staphylococcus aureus enmeshed in agar beads.
AB  - We describe a novel mouse model of acute staphylococcal pneumonia induced by
      intravenous injection of Staphylococcus aureus enmeshed in agar beads. For
      comparison, we also used various strains of bacteria, including three strains of
      S. aureus, two strains of Staphylococcus epidermidis, one strain of Streptococcus
      pyogenes, three strains of Pseudomonas aeruginosa, and one strain of Klebsiella
      pneumoniae. All except two strains of S. aureus were cleared rapidly from the
      lungs. When S. aureus NUMR1 enmeshed in agar beads was injected intravenously,
      the organisms concentrated and remained in the lung for a period longer than
      several weeks. Multiple lung abscesses were evident macroscopically, and
      histological examination of the infected lung showed multiple lung abscesses
      around the pulmonary arterioles, consisting of bacterial colonies encircled with
      fibrin filaments and surrounded by inflammatory cells of neutrophils and
      macrophages. When 14 strains of clinically isolated S. aureus were injected
      intravenously, the number of bacteria recovered from the lung tissue 7 days after
      infection correlated with the titer of staphylocoagulase (P < 0.01) but not with
      the titer of clumping factor. Injection of coagulase-deficient mutant strain
      DU5843 was associated with a markedly reduced number of viable bacteria isolated
      from the lung, compared with its coagulase-positive parental strain DU5789. Our
      results suggest that coagulase may play a role in the development of blood-borne
      staphylococcal pneumonia in our model. Our animal model is simple and
      reproducible and resembles blood-borne staphylococcal pneumonia in humans, and it
      could be useful for investigating the pathogenicity or treatment of
      staphylococcal pulmonary infection, including infections with methicillin
      resistant S. aureus.

PMID- 9009299
TI  - Identification of neutralizing epitopes on Pseudomonas aeruginosa elastase and
      effects of cross-reactions on other thermolysin-like proteases.
AB  - Monoclonal antibodies (MAbs) to a Burkholderia (Pseudomonas) cepacia 36-kDa
      protease (PSCP) which neutralize PSCP and Pseudomonas aeruginosa elastase but not
      P. aeruginosa alkaline protease have been isolated (C. Kooi et al., Infect.
      Immun. 62:2811-2817, 1994). These MAbs, designated 36-6-6 and 36-6-8, react with
      N-chlorosuccinimide cleavage products of P. aeruginosa elastase, consistent with
      the recognition of a 13.9-kDa fragment which contains the active site.
      Overlapping 9-mer peptides that span this region were synthesized. Neutralizing
      MAbs to PSCP reacted strongly with two peptides (341HGFTEQNSG349 and 395RYM
      DQPSRD403). Peptide 341HGFTEQNSG349 overlaps the motif 337HEXXH341, which has
      been found in many zinc-dependent endopeptidases. Peptide 395RYMDQPSRD403 lies
      between E361, which binds a zinc atom, and H420, which acts as a proton donor at
      the active site. Polyclonal rabbit sera raised against these peptides reacted
      with elastase on Western immunoblots and by enzyme-linked immunosorbent assay.
      With hide powder azure as the substrate, antisera to either HGFTEQNG and
      RYMDQPSRD completely neutralized the activities of elastase, thermolysin, Vibrio
      cholerae hemagglutinin/protease, and PSCP but had no effect on P. aeruginosa
      alkaline protease or the Serratia marcescens major protease. These results
      suggest that the MAbs recognize two different epitopes on P. aeruginosa elastase
      and that antibodies raised against synthetic peptides corresponding to either of
      these epitopes neutralize proteolytic activity.

PMID- 9009301
TI  - Localization by site-directed mutagenesis of the site in human complement factor
      H that binds to Streptococcus pyogenes M protein.
AB  - M-protein receptors located on Streptococcus pyogenes cells are known to bind
      human plasma protein factor H. Human factor H is composed of 20 short consensus
      repeat (SCR) domains containing approximately 60 amino acids each. Factor H
      controls the activation of the alternative pathway of complement in plasma. We
      have scanned the entire human factor H molecule by site-directed deletion
      mutagenesis, expressed the recombinant proteins in insect cells using the
      baculovirus system, and measured the binding of different purified mutant
      proteins to three strains of S. pyogenes. These studies have revealed that
      recombinant factor H lacking SCR domains 6 to 10 does not bind to wild-type M+ S.
      pyogenes JRS4. Experiments performed with S. pyogenes JRS251, in which both C
      repeat domains of M protein were deleted, demonstrated that all of the factor H
      mutant proteins bound weakly to these cells except those lacking the SCR region
      from domains 6 to 10. Neither human factor H nor any of the recombinant proteins
      bound to the M- strain JRS145. Our results indicate that the only binding site on
      human factor H that interacts with streptococcus M protein is located in SCR
      domains 6 to 10 of factor H and that regions of M protein outside the C-repeat
      domains are involved in binding factor H.

PMID- 9009300
TI  - Purification and characterization of Campylobacter rectus surface layer proteins.
AB  - Campylobacter rectus is a putative periodontopathogen which expresses a
      proteinaceous surface layer (S-layer) external to the outer membrane. S-layers
      are considered to play a protective role for the microorganism in hostile
      environments. The S-layer proteins from six different C. rectus strains (five
      human isolates and a nonhuman primate [NHP] isolate) were isolated, purified, and
      characterized. The S-layer proteins of these strains varied in molecular mass
      (ca. 150 to 166 kDa) as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. They all reacted with monospecific rabbit antiserum to the
      purified S-layer of C. rectus 314, but a quantitative enzyme-linked immunosorbent
      assay demonstrated a strong antigenic relationship among the five human strains,
      while the NHP strain, 6250, showed weaker reactivity. Amino acid composition
      analysis showed that the S-layers of four C. rectus strains contained large
      proportions of acidic amino acids (13 to 27%) and that >34% of the amino acid
      residues were hydrophobic. Amino acid sequence analysis of six S-layer proteins
      revealed that the first 15 amino-terminal amino acids were identical and showed
      seven residues of identity with the amino-terminal sequence of the Campylobacter
      fetus S-layer protein SapA1. CNBr peptide profiles of the S-layer proteins from
      C. rectus 314, ATCC 33238, and 6250 confirmed that the S-layer proteins from the
      human strains were similar to each other and somewhat different from that of the
      NHP isolate (strain 6250). However, the S-layer proteins from the two human
      isolates do show some structural heterogeneity. For example, there was a 17-kDa
      fragment unique to the C. rectus 314 S-layer. The amino-terminal sequence of this
      peptide had homology with the C. rectus 51-kDa porin and was composed of nearly
      50% hydrophobic residues. Thus, the S-layer protein from C. rectus has structural
      heterogeneity among different human strains and immunoheterogeneity with the NHP
      strain.

PMID- 9009302
TI  - Biochemical comparison of the Cu,Zn superoxide dismutases of Cryptococcus
      neoformans var. neoformans and Cryptococcus neoformans var. gattii.
AB  - Cu,Zn superoxide dismutases (SODs) have been purified to homogeneity from the two
      varieties of Cryptococcus neoformans, C. neoformans var. neoformans and var.
      gattii. The N-terminal amino acid sequences of the two enzymes were similar,
      though not identical, and demonstrated homology with Cu,Zn SODs from other
      organisms. SOD activity was present in supernatants from stationary-phase
      cultures of isolates of C. neoformans var. neoformans and was also present from
      the mid-log phase onwards in cultures of an acapsular mutant of C. neoformans
      var. neoformans. SOD activity was practically undetectable in culture
      supernatants from isolates of C. neoformans var. gattii. The C. neoformans var.
      neoformans SOD had a reduced relative molecular mass of 19 kDa, and in its
      nonreduced form the enzyme was present as a 125-kDa species. Isoelectric focusing
      indicated that four species with pIs of 5.9, 6.15, 6.35, and 6.6 were present.
      The equivalent reduced molecular mass of the C. neoformans var. gattii enzyme was
      19 kDa, with a single species present under nonreducing conditions (relative
      molecular mass of 145 kDa) with a pI of 7.5. The activities of the enzymes from
      both varieties were inhibited by KCN; however, the copper chelator
      diethyldithiocarbamate was inhibitory only against the C. neoformans var. gattii
      enzyme, as was sodium azide. The C. neoformans var. neoformans SOD was not
      affected by preincubation for 1 h at 70 degrees C, and it also retained most of
      its activity when incubated at 37 degrees C relative to its activity when
      incubated at 20 degrees C, in contrast to the C. neoformans var. gattii enzyme.
      The pronounced differences in the physical and biochemical characteristics of the
      Cu,Zn SODs from the two Cryptococcus varieties complement recent reports
      illustrating the biochemical and genetic differences between C. neoformans var.
      neoformans and C. neoformans var. gattii, and the successful purification of the
      two enzymes comprises the first step in determining what role, if any, the
      cryptococcal Cu,Zn SODs might have in protection against externally generated
      superoxide.

PMID- 9009304
TI  - In vitro infection of smooth muscle cells by Chlamydia pneumoniae.
AB  - Recent observations have shown that both Chlamydia pneumoniae antigens and DNA
      may be found within atherosclerotic lesions. In this study, we evaluated the
      ability of C. pneumoniae to infect cells that make up atherosclerotic lesions,
      including endothelial cells, smooth muscle cells, and cholesterol-loaded smooth
      muscle cells. The organism readily infected rabbit, bovine, and human aortic
      smooth muscle cells. Cholesterol-loaded smooth muscle cells were even more
      susceptible to C. pneumoniae infection. Chlamydia trachomatis inefficiently
      infected smooth muscle cells, demonstrating that this is not a characteristic of
      all members of the genus Chlamydia. C. pneumoniae infected bovine endothelial
      cells poorly. This study demonstrates that C. pneumoniae readily infects one of
      the important types of cells found within atherosclerotic lesions, i.e., smooth
      muscle cells with and without cholesterol loading.

PMID- 9009303
TI  - Characterization, occurrence, and molecular cloning of a 39-kilodalton Brucella
      abortus cytoplasmic protein immunodominant in cattle.
AB  - Monoclonal antibodies and polyclonal antisera recognizing a 39-kDa protein (P39)
      of brucellin, a cytoplasmic extract from Brucella melitensis rough strain B115,
      were produced. The P39 was purified by anion-exchange chromatography. Eleven of
      fourteen Brucella-infected cows whose infections had been detected by the delayed
      type hypersensitivity (DTH) test with brucellergen also developed a DTH reaction
      when purified P39 was used as the trigger. The T-cell proliferative responses to
      P39 of peripheral blood lymphocytes from Brucella-infected cows were also
      positive. None of the animals infected with other bacterial species that are
      presumed to induce immunological cross-reactions with Brucella spp. reacted to
      P39, either in DTH tests or in lymphocyte proliferation assays. A lambda gt11
      genomic library of Brucella abortus was screened with a monoclonal antibody
      specific for P39, and the gene coding for this protein was subsequently isolated.
      The nucleotide sequence of the P39 gene was determined, and the deduced amino
      acid sequence is in accordance with the sequence of an internal peptide isolated
      from P39.

PMID- 9009305
TI  - A new putative fimbrial colonization factor, CS19, of human enterotoxigenic
      Escherichia coli.
AB  - A gene probe derived from the colonization factor antigen I (CFA/I) operon cross
      hybridized at very low stringency to plasmid DNA from coli surface antigen 17
      (CS17)-producing enterotoxigenic Escherichia coli (ETEC) and from the ETEC strain
      F595C, which was negative for previously described CFAs, CSs, and putative
      colonization factors (PCFs). A 16-kDa protein was identified in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of heat extracts prepared after growth
      of strain F595C at 37 degrees C on CFA agar containing bile salts. Transmission
      electron microscopy revealed bile salt- and temperature-dependent expression of
      fimbriae with a diameter of 7 nm. After transformation with a recombinant plasmid
      harboring the cfaR gene, which encodes a positive regulator of several CFAs,
      PCFs, and CSs, the 16-kDa protein was hyperexpressed. Polyclonal antibodies
      raised against this protein bound to the fimbriae and inhibited the adhesion of
      F595C bacteria to tissue-cultured Caco-2 cells. Nucleotide sequence determination
      of the gene encoding the 16-kDa fimbrial subunit revealed a high degree of amino
      acid sequence homology to the CFA/I, CS1, CS2, CS4, CS14, and CS17 polypeptides.
      The term CS19 is proposed for the new fimbria.

PMID- 9009306
TI  - Identification, characterization, and immunogenicity of the lactoferrin-binding
      protein from Helicobacter pylori.
AB  - Iron acquisition plays an important role in bacterial virulence. Different
      studies have been initiated to define the mechanism by which Helicobacter pylori
      acquires iron. We had previously demonstrated that human lactoferrin (HLf)
      supported full growth of the bacteria in media lacking other iron sources. The
      ability of H. pylori to use HLf as an iron source had been found to be dependent
      on cell-to-protein contact. Since lactoferrin has been found in significant
      amounts in human stomach resection specimens from patients with superficial or
      atrophic gastritis, the iron uptake of H. pylori via a specific HLf receptor may
      play a major role in the virulence of H. pylori infection. In this study, by
      using affinity chromatography with biotinylated HLf and streptavidin-agarose, we
      identified a 70-kDa lactoferrin-binding protein (Lbp) from outer membrane
      proteins of H. pylori. This Lbp was only present when H. pylori was grown in an
      iron-starved medium, suggesting that it serves in iron uptake. Direct binding
      assays with increasing concentrations of biotinylated HLf demonstrated that the
      lactoferrin interaction with the outer membrane of H. pylori grown in iron
      restricted medium was saturable. Competitive binding experiments with bovine and
      human lactoferrin and with transferrin of horse, bovine, and human origin
      indicated that this Lbp appeared highly specific for HLf. A number of other
      studies have focused on the importance of transferrin and lactoferrin receptors
      in pathogenic bacteria and their specificity with the host species. This
      observation might explain the very strict human specificity of H. pylori.

PMID- 9009307
TI  - A 140-kilodalton extracellular protein is essential for the accumulation of
      Staphylococcus epidermidis strains on surfaces.
AB  - Two distinct pathogenic mechanisms, adhesion to polymer surfaces and subsequent
      accumulation of sessile bacterial cells, are considered important pathogenic
      steps in foreign body infections caused by Staphylococcus epidermidis. By using
      mitomycin mutagenesis, we have recently generated a mutant, strain M7, from S.
      epidermidis RP62A which is unaffected in adhesion but deficient in accumulation
      on glass or polystyrene surfaces and lacks a 115-kDa extracellular protein
      (designated the 140-kDa antigen; F. Schumacher-Perdreau, C. Heilmann, G. Peters,
      F. Gotz, and G. Pulverer, FEMS Microbiol. Lett. 117:71-78, 1994). To evaluate the
      role of this protein in accumulation, we harvested extracellular proteins from S.
      epidermidis RP62A grown on dialysis membranes placed over chemically defined
      medium, purified the protein by using ion-exchange chromatography, determined its
      N-terminal amino acid sequence, and raised antiserum in rabbits. The antibody
      recognized only a single band in a Western immunoblot of the crude extracellular
      extract. With the microtiter biofilm test, antiserum at a dilution of < or
      =1:1,000 blocked accumulation of RP62A up to 98% whereas preimmune serum did not.
      The 140-kDa antigen was found only in extracellular products from bacteria grown
      under sessile conditions. Of 58 coagulase-negative clinical isolates, 32 strains
      were 140-kDa antigen positive and produced significantly larger amounts of
      biofilm than the 26 strains that were 140-kDa antigen negative. The 140-kDa
      protein appears to be biochemically and functionally unrelated to any previously
      described factors associated with biofilm formation. Thus, the 140-kDa antigen,
      referred to as accumulation-associated protein, may be a factor essential in S.
      epidermidis accumulation and, due to its immunogenicity, may allow the
      development of novel immunotherapeutic strategies for prevention of foreign body
      infection.

PMID- 9009308
TI  - A role for B cells in resistance to Cryptococcus neoformans in mice.
AB  - The role of B cells in immunity to Cryptococcus neoformans was investigated.
      Genetically targeted, B-cell-deficient mice (mu Mt) examined at various times
      after intravenous infection with C. neoformans 184 had lung and brain yeast
      burdens that were equivalent to tissue burdens in control B-cell-sufficient mice.
      Both B-cell-deficient and B-cell-sufficient control mice were effectively
      vaccinated by a sublethal intratracheal instillation of strain 184 yeast against
      a systemic infection with the C. neoformans strain carrying ura5; vaccinated
      control and vaccinated B-cell-deficient mice had equivalent brain and lung
      burdens of the ura5 strain 10 days after intravenous rechallenge. Additionally, B
      cell-deficient and B-cell-sufficient vaccinated mice survived an intravenous
      rechallenge with a dose of yeast cells which is normally lethal for unimmunized
      mice. In further studies of the role of B cells in murine cryptococcosis, SCID
      mice were reconstituted with lymphocytes from B-cell-deficient and B-cell
      sufficient mice. SCID mice reconstituted with lymphocytes from vaccinated B-cell
      deficient animals failed to express effective adoptive immunity to C. neoformans
      brain infection. In contrast, SCID mice reconstituted with lymphocytes from
      vaccinated B-cell-sufficient mice had 10-fold fewer yeast cells in their brains
      than did uninfused SCID controls. However, SCID mice given lymphocytes from B
      cell-deficient immune donors had fewer yeast cells in their lungs than did
      uninfused controls. Fewer CD4+ lymphocytes were recovered at 7 and 11 days after
      infection from the peripheral blood and spleens of SCID mice reconstituted with
      lymphocyte suspensions from B-cell-deficient animals than from the peripheral
      blood and spleens of SCID mice reconstituted with suspensions from B-cell
      sufficient control donors. These data suggest that B cells can play an important
      role in host defense against Cryptococcus in the brain under conditions in which
      T-cell-mediated immunity is impaired.

PMID- 9009309
TI  - Escherichia coli K5 capsule expression enhances colonization of the large
      intestine in the gnotobiotic rat.
AB  - The role of capsule expression in the capacity of Escherichia coli to colonize in
      the large intestinal environment was studied in a gnotobiotic rat model. The rats
      were given perorally a mixture of two mutant strains differing in K5 expression.
      After 2 weeks, the rats were sacrificed, and subsequently intestinal contents,
      intestinal mucosae, and mesenteric lymph nodes were homogenized and bacterial
      numbers were quantified. Two E. coli mutant pairs were used, the first pair (972
      998) lacking the O-specific side chain and the second pair (973-997) carrying the
      O75 lipopolysaccharide. The K5+ mutants established themselves at a higher level
      than the K5- mutants (10(9) versus 10(6) CFU/g [P < 0.001] for the first pair and
      10(9) versus 10(8) CFU/g [P < 0.01] for the second pair, respectively). The
      results were confirmed by serology showing a K5+ phenotype for practically all
      isolates. The bacterial population associated with the mucosa was similar to that
      in the luminal contents with respect to the proportions of the respective
      mutants, and translocation occurred in numbers proportional to the intestinal
      population densities of the respective mutants. All mutants were able to express
      type 1 as well as P fimbriae. After colonization, the expression of P fimbriae
      remained high whereas only a minority of the isolates expressed type 1 fimbriae.
      The results suggest that capsule expression and P fimbriae enhance intestinal
      colonization by E. coli and that these virulence factors, by increasing bacterial
      densities in the intestine, secondarily increase translocation.

PMID- 9009310
TI  - Identification of D motif epitopes in Staphylococcus aureus fibronectin-binding
      protein for the production of antibody inhibitors of fibronectin binding.
AB  - A fibronectin-binding protein (FnBP) adhesin of Staphylococcus aureus possesses
      three 37- or 38-amino-acid motifs (D1, D2, and D3) that can each bind fibronectin
      (Fn) with low affinity and that in tandem comprise D1-3, a high-affinity Fn
      binding domain. To identify epitopes for the generation of adhesion-blocking
      antibodies, rabbits were immunized with recombinant D1-3 or with a glutathione S
      transferase fusion protein, GSTD1-3. Affinity-purified antibodies from the D1-3
      immunization were poor inhibitors of Fn binding to S. aureus and recognized
      several different epitopes, with a preference for clusters of acidic amino acids
      that do not contribute to Fn binding. Antibodies generated with GSTD1-3 as an
      immunogen were more effective inhibitors, but concentrations in excess of 20
      microg x ml-1 did not promote more than 50% inhibition. These antibodies were
      highly specific for amino acids 21 to 34 of D1 (D1(21-34)), which contain a
      sequence that is essential for Fn binding and are identical to D2 at 12 of 14
      residues. Neither antibody preparation recognized D3(20-33) of the D3 motif,
      where the only homology to D1(21-34) and D2(21-34) comprises a sequence motif,
      GG(X3,4)(I/V)DF, that is critical to Fn binding. However, antibodies specific for
      both D1(21-34) and D3(20-33) could be obtained by using synthetic peptides
      corresponding to these sequences as immunogens. F(ab')2 fragments derived from
      these antibodies each caused 40 to 50% inhibition of Fn binding to S. aureus, and
      their ability to bind to purified FnBP was eliminated by competing Fn. However,
      mixtures of the two F(ab')2 preparations did not provide additive or synergistic
      inhibition of Fn binding. Therefore, inhibition of Fn binding to S. aureus
      requires antibodies specific for D1(21-34) and D3(20-33), but a mixture of
      antibodies specific for both sequences did not provide complete inhibition.

PMID- 9009311
TI  - Intranasal priming with recombinant Bordetella pertussis for the induction of a
      systemic immune response against a heterologous antigen.
AB  - One of the current goals in vaccine development is the noninvasive administration
      of protective antigens via mucosal surfaces. In this context, the gut-associated
      lymphoid tissues have already been extensively explored. Vaccination via the
      nasal route has only recently been the focus of intensive investigation, and no
      live vector specifically designed for the respiratory mucosa is yet available. In
      this study we show that intranasal administration of the recombinant Bordetella
      pertussis BPGR60, producing the Schistosoma mansoni 28-kDa glutathione S
      transferase (Sm28GST) protective antigen fused to filamentous hemagglutinin,
      induces priming in mice for the production of serum antibodies. In addition to
      significant levels of anti-Sm28GST immunoglobulin A (IgA) antibodies, high levels
      of anti-Sm28GST serum antibodies were obtained after intranasal boost with the
      purified antigen or infection with S. mansoni following intranasal priming with
      BPGR60. These antibodies were of the IgG1, IgG2a, and IgG2b isotypes, suggesting
      a mixed immune response. No priming was observed in animals that had received
      nonrecombinant B. pertussis or purified Sm28GST, indicating specific priming by
      BPGR60. This priming was also evident in immune protection against S. mansoni
      challenge. Significant protection against worm burden and egg output was obtained
      in mice primed with BPGR60 and intranasally boosted with purified Sm28GST. A
      lower but still significant degree of protection against egg output was also
      obtained in mice infected with a single dose of BPGR60. These results indicate
      that intranasal administration of recombinant B. pertussis can prime for serum
      antibody responses against a foreign antigen and for heterologous protection.

PMID- 9009312
TI  - Role of aspartic proteases in disseminated Candida albicans infection in mice.
AB  - A murine model of disseminated candidiasis involving intranasal challenge with
      Candida albicans was developed and used to explore the role of C. albicans
      aspartic proteases as virulence factors during early dissemination. Pretreatment
      of neutropenic mice with the aspartic protease inhibitor pepstatin A by
      intraperitoneal injection afforded strong dose-dependent protection against a
      subsequent lethal intranasal dose of an aspartic protease-producing strain (ATCC
      32354) of C. albicans. Administration of 0.6 mg of pepstatin A kg of body weight(
      1) prior to challenge and on days 1 to 4 postchallenge resulted in 100% survival
      at day 15 postchallenge, whereas 100% of animals receiving saline had died by day
      6. This effect was comparable to the dose-dependent protection obtained with
      amphotericin B, which resulted in 100% survival when administered at 0.1 mg kg(
      1). The reduction in mortality afforded by pepstatin A correlated with its dose
      dependent blockade of C. albicans numbers in the lungs, liver, and kidneys. By
      sharp contrast, no protection by pepstatin A was observed in mice challenged
      intravenously, and protection was markedly attenuated in mice given pepstatin A
      after intranasal challenge only. These data show the utility of pepstatin A in
      the prophylaxis of disseminated Candida infections and suggest that Candida
      aspartic proteases play an essential role early in dissemination.

PMID- 9009313
TI  - Cryptococcal polysaccharides bind to CD18 on human neutrophils.
AB  - CD18, the beta chain of the beta 2 integrin family of adhesion molecules, is
      associated with three different alpha chains (CD11a, -b, and -c) and is expressed
      on the surface of all types of leukocytes. CD18-containing molecules are up
      regulated on the surface of neutrophils (polymorphonuclear cells [PMN]) in
      response to chemotactic agents and are implicated in mediating adhesion to an
      inflamed endothelium, which is a prerequisite to migration of PMN into infected
      tissues. In a previous study, we found that a cryptococcal culture filtrate
      (CneF), when injected into the bloodstream of mice to simulate the antigenemia in
      cryptococcosis, inhibits PMN accumulation at the site of an inflammatory
      stimulus. In the present study, we assessed the ability of CneF and its
      individual components, i.e., glucuronoxylomannan (GXM), galactoxylomannan
      (GalXM), and mannoprotein (MP), to interact with CD18 on human PMN. CneF labeled
      with 14C was shown to bind to human PMN in a dose-dependent manner. Pretreatment
      of PMN with anti-CD18, but not an isotype-matched control monoclonal antibody
      (MAb) or anti-CD11a MAb, blocked the binding of 14C-labeled CneF to PMN. In
      addition, CneF, GXM, and GalXM but not MP significantly blocked the binding of
      the anti-CD18 MAb to CD18 on the surface of unactivated and formyl methionyl
      leucyl phenylalanine-activated PMN as determined by indirect immunofluorescence
      staining and flow cytometric analysis. In the same experiments, the cryptococcal
      polysaccharides did not affect the binding of an anti-CD11a or anti-L-selectin
      MAb to the surface of PMN at 4 degrees C. The results suggest that CneF and its
      components GXM and GalXM bind to CD18 on human PMN. Based on our findings, we
      propose that CD18 is a possible molecular target of cryptococcal polysaccharides
      and that binding of the polysaccharides to CD18 has the potential to inhibit
      leukocyte infiltration into inflammatory sites.

PMID- 9009314
TI  - Th1 and Th2 cytokines in mice with invasive aspergillosis.
AB  - With a murine model of invasive aspergillosis we investigated cytokine production
      by CD4+ T helper cells and the effects of cytokine administration or
      neutralization on the course and outcome of infection. Patterns of susceptibility
      and resistance to infection were obtained with different strains of mice injected
      with different inocula of Aspergillus fumigatus conidia. Mice surviving the
      primary infection also resisted a subsequent lethal infection that was associated
      with production of gamma interferon by CD4+ T splenocytes. Impaired neutrophil
      antifungal activity, observed in susceptible mice, was concomitant with a
      predominant production of interleukin-4 (IL-4) by CD4+ splenocytes. In these
      mice, exogenous administration of IL-12 failed to induce resistance to infection;
      in contrast, treatment with soluble IL-4 receptor cured more than 70% of the mice
      from primary infection and resulted in the onset of acquired resistance to a
      subsequent lethal infection. These findings indicate that in murine invasive
      aspergillosis, production of IL-4 by CD4+ T cells may be one major factor
      discriminating susceptibility and resistance to infection.

PMID- 9009315
TI  - Topology of Legionella pneumophila DotA: an inner membrane protein required for
      replication in macrophages.
AB  - The Legionella pneumophila dotA gene is required for intracellular growth of the
      bacterium in macrophages. In this study, a structure-function analysis of the
      DotA protein was conducted to elucidate the role of this protein in L.
      pneumophila pathogenesis. Translational fusions of dotA to the Escherichia coli
      phoA and lacZ genes indicated that DotA is an integral cytoplasmic membrane
      protein with eight membrane-spanning domains. DotA contains two large periplasmic
      domains of approximately 503 and 73 amino acids and a carboxyl-terminal
      cytoplasmic domain of 122 amino acids. Protein fractionation studies were
      consistent with DotA residing in the inner membrane. An alkaline phosphatase
      fusion located 9 amino acids upstream from the C terminus of DotA still retained
      function and was able to restore intracellular growth when harbored by two L.
      pneumophila dotA mutants. A hybrid protein from which the carboxyl-terminal 48
      amino acids of DotA were deleted was unable to complement the intracellular
      growth defect in the dotA mutants, indicating that this cytoplasmic region is
      required for function.

PMID- 9009316
TI  - Pseudomonas aeruginosa-mediated cytotoxicity and invasion correlate with distinct
      genotypes at the loci encoding exoenzyme S.
AB  - Pseudomonas aeruginosa, an opportunistic pathogen, is capable of establishing
      both chronic and acute infections in compromised hosts. Previous studies
      indicated that P. aeruginosa displays either a cytotoxic or an invasive phenotype
      in corneal epithelial cells. In this study, we used polarized MDCK cells for in
      vitro infection studies and confirmed that P. aeruginosa isolates can be broadly
      differentiated into two groups, expressing either a cytotoxic or an invasive
      phenotype. In vivo infection studies were performed to determine if cytotoxic and
      invasive strains displayed differential pathology. Invasion was assayed in vivo
      by in situ infection of mouse tracheal tissue followed by electron microscopy.
      Both cytotoxic and invasive strains entered mouse tracheal cells in situ;
      however, more necrosis was associated with the cytotoxic strain. In an acute lung
      infection model in rats, cytotoxic strains were found to damage lung epithelium
      more than invasive strains during the short infection period of this assay. The
      expression of cytotoxicity requires a functional exsA allele. In the strains
      tested, the ability to invade epithelial cells in vitro appears to be independent
      of exsA expression. Since ExsA is a transcriptional regulator of the exoenzyme S
      regulon, chromosomal preparations from invasive and cytotoxic strains were
      screened for their complement of exoenzyme S structural genes, exoS, encoding the
      49-kDa ADP-ribosyltransferase (ExoS), and exoT, encoding the 53-kDa form of the
      enzyme (Exo53). Invasive strains possess both exoS and exoT, while cytotoxic
      strains appear to have lost exoS and retained exoT. These data indicate that the
      expression of cytotoxicity may be linked to the expression of Exo53, deletion of
      exoS and perhaps other linked loci, or expression of other ExsA-dependent
      virulence determinants. In the absence of a functional cytotoxicity pathway
      (exsA::omega strains), invasion of eukaryotic cells is detectable.

PMID- 9009317
TI  - Simultaneous prevention of glutamine synthesis and high-affinity transport
      attenuates Salmonella typhimurium virulence.
AB  - In Salmonella typhimurium, transcription of the glnA gene (encoding glutamine
      synthetase) is under the control of the nitrogen-regulatory (ntr) system
      comprising the alternate sigma factor sigma54 (NtrA) and the two-component sensor
      transcriptional activator pair NtrB and NtrC. The glnA, ntrB, and ntrC genes form
      an operon. We measured the virulence of S. typhimurium strains with nitrogen
      regulatory mutations after intraperitoneal (i.p.) or oral inoculations of BALB/c
      mice. Strains with single mutations in glnA, ntrA, ntrB, or ntrC had i.p. 50%
      lethal doses (LD50s) of <10 bacteria, similar to the wild-type strain. However, a
      strain with a delta(glnA-ntrC) operon deletion had an i.p. LD50 of >10(5)
      bacteria, as did delta glnA ntrA and delta glnA ntrC strains, suggesting that
      glnA strains require an ntr-transcribed gene for full virulence. High-level
      transcription of the glutamine transport operon (glnHPQ) is dependent upon both
      ntrA and ntrC, as determined by glnHp-lacZ fusion measurements. Moreover, delta
      glnA glnH and delta glnA glnQ strains are attenuated, similar to delta glnA ntrA
      and delta glnA ntrC strains. These results reveal that access of S. typhimurium
      to host glutamine depends on the ntr system, which apparently is required for the
      transcription of the glutamine transport genes. The delta(glnA-ntrC) strain
      exhibited a reduced ability to survive within the macrophage cell line J774,
      identifying a potential host environment with low levels of glutamine. Finally,
      the delta(glnA-ntrC) strain, when inoculated at doses as low as 10 organisms,
      provided mice with protective immunity against challenge by the wild-type strain,
      demonstrating its potential use as a live vaccine.

PMID- 9009318
TI  - Stabilized expression of mRNA is associated with mycobacterial resistance
      controlled by Nramp1.
AB  - Control of innate resistance to the growth of mycobacteria is mediated by a gene
      termed Nramp1. Although the role of the protein product of Nramp1 in mediating
      resistance to mycobacterial growth is not known, the effect of the gene is
      pleiotropic and it has been suggested that the gene controls macrophage priming
      for activation. We have found that the functional capacity of macrophages from
      Mycobacterium bovis BCG-susceptible mice can be suppressed by corticosterone,
      while the function of macrophages from BCG-resistant mice remains unaffected. In
      this study, we show that corticosterone differentially affects the stability of
      mRNAs of several recombinant gamma interferon (rIFN-gamma)-induced genes.
      Treatment of macrophages from BCG-susceptible mice with corticosterone
      accelerates the decay of Nramp1 mRNA. The mRNA of IFN-gamma-induced genes of
      macrophages from BCG-resistant mice was more stable than the mRNA of macrophages
      from BCG-susceptible mice in the presence or absence of corticosterone. The
      results of this investigation suggest that Nramp1 acts by stabilizing the mRNA of
      genes associated with macrophage activation, thus accounting for the functional
      differences that have been attributed to these macrophage populations.

PMID- 9009319
TI  - Helicobacter pylori lipopolysaccharide can activate 70Z/3 cells via CD14.
AB  - Helicobacter pylori persistently colonizes the human gastrointestinal tract and
      is associated with chronic gastritis and, in some cases, peptic ulcer disease or
      gastric neoplasms. One factor in the persistence of this organism may be its
      inability to elicit a strong inflammatory response. Lipopolysaccharide (LPS) is a
      proinflammatory substance found in the cell walls of all gram-negative bacteria.
      H. pylori LPS has been found by several different measures to be less active than
      LPS from Enterobacteriaceae. This study addresses the role of CD14 and LPS
      binding protein in the cellular response to H. pylori LPS. We report that H.
      pylori LPS activates mammalian cells expressing CD14 at much lower LPS
      concentrations than those for control cells not expressing CD14. The maximal
      activation of CD14-70Z/3 cells by H. pylori LPS also requires LPS-binding
      protein. H. pylori LPS at concentrations as high as 30 microg/ml does not elicit
      an interleukin-8 (IL-8) response from the epithelial cell line SW620 in the
      presence of CD14; 10 ng of Escherichia coli LPS per ml elicits a maximal IL-8
      response. Furthermore, in contrast to some other types of LPS with little
      activity, H. pylori LPS does not inhibit the CD14-70Z/3 cell response to E. coli
      LPS. From these studies, we conclude that H. pylori LPS, though much less active
      than E. coli LPS, stimulates cells via CD14.

PMID- 9009320
TI  - The central variable V2 region of the CS31A major subunit is involved in the
      receptor-binding domain.
AB  - CS31A is a K88-related capsule-like surface protein that mediates Escherichia
      coli and Klebsiella pneumoniae adhesion to the human Caco-2 and Intestine-407
      cell lines. In this study, we demonstrate that ClpG, the major subunit of CS31A,
      contains the adhesive domain of the polymerized structure. We mapped this domain
      within the ClpG protein by performing adhesion inhibition experiments with
      Intestine-407 cells with nine synthetic peptides (CLP1 to CLP9) covering the
      dominant antigenic regions of ClpG and with the corresponding rabbit antipeptide
      antibodies. The peptides CLP1 (amino acid positions in parentheses) (5-18), CLP2
      (44-56), CLP3 (82-96), CLP7 (174-190), CLP8 (185-199), and CLP9 (235-249) and
      corresponding antipeptide antibodies targeting parts of the N- and C-terminal
      regions of ClpG had no effect on the adhesion of the TCFF15 recombinant strain
      expressing CS31A. Only the CLP5 (132-146) peptide, corresponding to the central
      part of the protein, and relevant antibodies inhibited bacterial adhesion to
      intestinal epithelial cells. Anti-CLP4 (97-109) and anti-CLP6 (148-162)
      antibodies targeting regions surrounding the CLP5 sequence also inhibited
      bacterial adhesion. Site-directed mutagenesis experiments inducing changes in the
      amino acid sequence of the ClpG protein corresponding to the CLP5 peptide
      resulted in the expression of nonadhesive CS31A antigen. These findings indicate
      that the ClpG receptor-binding domain is located in the central variable V2
      region.

PMID- 9009321
TI  - Induction of biologically active interleukin-8 from lung epithelial cells by
      Burkholderia (Pseudomonas) cepacia products.
AB  - The frequency of isolation of Burkholderia cepacia from the sputum of cystic
      fibrosis (CF) patients is increasing. Using the human A549 lung epithelial cell
      line, we have investigated the ability of B. cepacia exoproducts to stimulate
      interleukin-8 (IL-8) release. Cell-free supernatants from a panel of CF clinical,
      non-CF clinical, and nonclinical B. cepacia isolates were found to stimulate IL-8
      release, with levels ranging from 11.8 +/- 2.8 to 80.0 +/- 3.5 ng/ml. A similar
      pattern was seen at the level of the IL-8 mRNA. The bioactivity of the IL-8 was
      confirmed by examining its effect on the intracellular free calcium in
      neutrophils and inhibition by a neutralizing anti-IL-8 antibody. B. cepacia
      lipopolysaccharide, which was able to stimulate IL-8 release from monocytes, did
      not release IL-8 from the A549 cells. Furthermore, the stimulating ability of the
      bacterial cell-free supernatant was not diminished by polymyxin B, was markedly
      reduced by boiling, and appeared unrelated to N-acylhomoserine lactones. The
      ability of B. cepacia to elicit IL-8 release from epithelial cells may be
      important in the pathology of CF.

PMID- 9009322
TI  - Adjuvant modulation of immune responses to tuberculosis subunit vaccines.
AB  - Mice were immunized with experimental subunit vaccines based on secreted antigens
      from Mycobacterium tuberculosis in a series of adjuvants, comprising incomplete
      Freund's adjuvant (IFA), dimethyl dioctadecyl ammoniumbromide (DDA), RIBI
      adjuvant, Quil-A saponin, and aluminum hydroxide. Immune responses induced by
      these vaccines were characterized by in vitro culture of primed cells, PCR
      analysis for cytokine mRNA, detection of specific immunoglobulin G isotypes
      induced, and monitoring of protective immunity to tuberculosis (TB). The study
      demonstrated marked differences in the immune responses induced by the different
      adjuvants and identified both IFA and DDA as efficient adjuvants for a TB subunit
      vaccine. Aluminum hydroxide, on the other hand, induced a Th2 response which
      increased the susceptibility of the animals to a subsequent TB challenge. DDA was
      further coadjuvanted with either the Th1-stimulating polymer poly(I-C) or the
      cytokines gamma interferon, interleukin 2 (IL-2), and IL-12. The addition of IL
      12 was found to amplify a Th1 response in a dose-dependent manner and promoted a
      protective immune response against a virulent challenge. However, if the initial
      priming in the presence of IL-12 was followed by two booster injections of
      vaccine without IL-12, no improvement in long-term efficacy was found. This
      demonstrates the efficacy of DDA to promote an efficient immune response and
      suggests that IL-12 may accelerate this development, but not change the final
      outcome of a full vaccination regime.

PMID- 9009323
TI  - Critical roles of neutrophils in host defense against experimental systemic
      infections of mice by Listeria monocytogenes, Salmonella typhimurium, and
      Yersinia enterocolitica.
AB  - This study shows that neutrophils are critical for combating experimental
      systemic infections of mice by the bacterial pathogens Listeria monocytogenes,
      Salmonella typhimurium, and Yersinia enterocolitica. It shows that mice rendered
      neutropenic by treatment with the granulocyte-depleting monoclonal antibody RB6
      8C5 are far more susceptible than immunocompetent mice to infection with each of
      these three pathogens. Compared to immunocompetent mice, neutropenic mice exhibit
      several defects in their antibacterial capabilities. Firstly, the immediate
      inactivation of Listeria, Salmonella, or Yersinia that initially implants in the
      livers and spleens that occurs in immunocompetent mice is abolished in these
      organs in neutropenic mice. Secondly, unlike immunocompetent mice, neutropenic
      mice neither control the subsequent proliferation of the inoculated bacteria in
      the livers and spleens nor prevent dissemination of infection to other organs.
      Thirdly, mice rendered neutropenic develop a generalized leukopenia in response
      to these three infections. Overall, this study indicates that neutrophils perform
      diverse antimicrobial functions that, combined, severely restrict the rate at
      which Listeria, Salmonella, and Yersinia multiply in the tissues during the
      preimmune phase of infection and thereby provide the host with the opportunity to
      develop and express more efficient specific protective immunity.

PMID- 9009324
TI  - Protegrin structure and activity against Neisseria gonorrhoeae.
AB  - Protegrin 1 (PG-1) is a broad-spectrum antimicrobial peptide that contains 18
      amino acid residues (RG GRLCYCRRRFCVCVGR) and has two intramolecular cystine
      disulfide bonds. To determine the minimal structure responsible for protegrin
      mediated activity against Neisseria gonorrhoeae, we synthesized 15 protegrin
      variants and tested them against two well-characterized gonococcal strains. The
      MICs of PG-1 were 0.61 microM (1.31 microg/ml) for the serum-sensitive strain F
      62 and 0.98 microM (2.11 microg/ml) for the serum-resistant strain FA 19. Six
      amino acid residues (Arg1, Gly2, Gly3, Arg4, Gly17, and Arg18) and either
      disulfide bond could be deleted from PG-1 without impairing its potency against
      strain F 62. In contrast, only Gly17 and Arg18 could be removed without
      decreasing its activity against FA 19. Protegrin congener 64a (PC-64a;
      LTYCRRRFCVTV), a variant of PG-1 with 12 amino acid residues and one disulfide
      bond, displayed MICs of 0.45 microM (0.68 microg/ml) for strain F 62 and 1.37
      microM (2.07 microg/ml) for strain FA 19, which approximated those of intact PG
      1. Serum-sensitive sac-1+ and sac-3+ transformants of N. gonorrhoeae FA 19 and
      two FA 19 derivatives with truncated lipooligosaccharide structures were more
      susceptible to PG-1 and variants with altered disulfide structures. These data
      suggest that structurally simpler protegrin variants, such as PC-64a, could be
      used as topical microbicides for N. gonorrhoeae. They also suggest that the
      cystine-stabilized antiparallel beta-sheet formed by PG-1 residues 5 to 16 is
      principally responsible for its activity against gonococci.

PMID- 9009325
TI  - Oral immunization with PspA elicits protective humoral immunity against
      Streptococcus pneumoniae infection.
AB  - Streptococcus pneumoniae is a major respiratory mucosal pathogen affecting
      infants and children. Although a polysaccharide-based vaccine has been useful in
      adult populations, it does not elicit protective immunity in infants and young
      children. Pneumococcal surface protein A (PspA) is a highly immunogenic surface
      protein produced by all strains of Streptococcus pneumoniae. Previous studies
      have shown that systemic immunization of mice with PspA can elicit protective
      immunity against fatal pneumococcal infection. In this study, we demonstrated
      that oral immunization with PspA could elicit protective immune responses against
      pneumococcal infection. When mice were orally immunized with PspA alone, low
      levels of PspA-specific immunoglobulin G (IgG) responses were induced in serum;
      none was induced in secretion. On the other hand, when PspA was given orally with
      the mucosal adjuvant cholera toxin (CT), significant levels of IgG and IgA anti
      PspA responses were induced in serum. The major IgG subclass was IgG1, followed
      by IgG2b, a profile of antibody response supported by Th2-type cells. In
      addition, all mice orally immunized with PspA and CT were protected from the
      lethal challenge with capsular serotype 3 S. pneumoniae A66. These results
      suggested that an oral PspA vaccine may be a useful means of preventing
      pneumococcal disease.

PMID- 9009326
TI  - Selection of Opa+ Neisseria gonorrhoeae by limited availability of normal human
      serum.
AB  - Experimental infections of human male volunteers with Neisseria gonorrhoeae have
      provided valuable insights into the early stages of gonorrheal disease. Bacterial
      variants expressing outer membrane opacity (Opa) proteins appear to be selected
      from the inoculum during a period in which total recoverable numbers of bacteria
      decrease rapidly. This apparent survival advantage occurs simultaneously with the
      onset of an inflammatory response, characterized by local production of
      interleukin 6 (IL-6) and IL-8 and the appearance of leukocytes in urine. Since
      the inflammatory response may also result in the presence of serum factors on the
      mucosal surface, we investigated the possibility that killing in normal human
      serum (NHS) leads to the selection of Opa+ variants. We therefore studied killing
      of separate populations and mixtures of Opa- and Opa+ N. gonorrhoeae MS11mk in
      NHS. Expression of an Opa protein conferred a survival advantage upon the
      organism; i.e., the Opa+ variants were more serum resistant than their isogenic
      Opa- counterparts, resulting in a selection for Opa+ phenotypes when a mixture of
      Opa+ and Opa- gonococci (GC) was exposed to submaximal doses of NHS. This
      selection was observed in three different lipooligosaccharide (LOS) backgrounds,
      indicating that it was not due to a difference in LOS expression between Opa- and
      Opa+ phenotypes. Incubation in NHS of sialylated GC resulted in a similar
      selection for Opa+ variants. The presence of normal human urine during the serum
      killing assay had no effect on the selection phenomenon but drastically depleted
      NHS of bactericidal activity, which was found to be at least partly due to
      complement inhibition. The results suggest that serum killing may contribute to
      the transition from Opa- to Opa+ phenotypes during the early stages of infection
      of the male urethra.

PMID- 9009327
TI  - Identification of tandem genes involved in lipooligosaccharide expression by
      Haemophilus ducreyi.
AB  - A transposon insertion mutant of Haemophilus ducreyi 35000 possessing a truncated
      lipooligosaccharide (LOS) failed to bind the LOS-specific monoclonal antibody 3E6
      (M. K. Stevens, L. D. Cope, J. D. Radolf, and E. J. Hansen, Infect. Immun.
      63:2976-2982, 1995). This transposon was found to have inserted into the first of
      two tandem genes and also caused a deletion of chromosomal DNA upstream of this
      gene. These two genes, designated lbgA and lbgB, encoded predicted proteins with
      molecular masses of 25,788 and 40,236 Da which showed homology with proteins
      which function in lipopolysaccharide biosynthetic in other gram-negative
      bacteria. The tandem arrangement of the lbgA and lbgB genes was found to be
      conserved among H. ducreyi strains. Isogenic LOS mutants, constructed by the
      insertion of a cat cartridge into either the lbgA or the lbgB gene, expressed an
      LOS phenotype indistinguishable from that of the original transposon-derived LOS
      mutant. The wild-type LOS phenotype could be restored by complementation with the
      appropriate wild-type allele. These two LOS mutants proved to be as virulent as
      the wild-type parent strain in an animal model. A double mutant with a deletion
      of the lbgA and lbgB genes yielded equivocal results when its virulence was
      tested in an animal model.

PMID- 9009328
TI  - Oral carriage of Candida albicans in murine AIDS.
AB  - Oral candidiasis is a common fungal infection in patients infected with the human
      immunodeficiency virus (HIV). Although rare at the time of primary HIV infection,
      it is frequently found throughout the asymptomatic phase and is predictive of
      progressive immunodeficiency. However, the precise immune defect which results in
      outgrowth of commensal Candida albicans in HIV infection has not been identified.
      Mice infected with the Du5H(G6T2) mixture of mouse leukemia viruses develop a
      syndrome, designated murine AIDS (MAIDS), that has many of the immune
      abnormalities found in HIV infection. Retrovirus-infected C57BL/6 mice were
      examined for their ability to resist the development of oral candidiasis from the
      carrier state established after a self-limiting acute infection and to clear a
      subsequent secondary inoculum of oral C. albicans. Most of the mice orally
      colonized with C. albicans and then inoculated with the retrovirus mixture
      maintained a low-level oral carriage of C. albicans, while 30% of coinfected mice
      developed recurring 2- to 3-week episodes of acute Candida proliferation,
      separated by transient recoveries to the carrier state. The frequencies of CD4+
      and CD8+ lymphocytes were, respectively, unchanged and significantly decreased (P
      < 0.05) in both cervical lymph nodes and spleens of coinfected mice compared to
      the corresponding frequencies in C. albicans-carrying, virus-free, age-matched
      control animals. Secretion of gamma interferon by concanavalin A (ConA)
      stimulated spleen cells from Candida-carrying, retrovirus-infected mice was
      significantly decreased (P < 0.05) compared to that of C. albicans-carrying,
      retrovirus-free mice, in accordance with known abnormalities associated with
      MAIDS. However, production of this cytokine by ConA-stimulated or unstimulated
      cervical lymph node cells from coinfected mice was enhanced compared to that of
      virus-free animals colonized with C. albicans. Acquired resistance to reinfection
      with C. albicans was maintained in retrovirus-infected mice and was associated
      with a mucosal recruitment of CD8+ cells not observed in control mice. These
      results suggest that alterations in mucosal immunity which occur in MAIDS differ
      substantially from defects observed at other sites and that surrogate epithelial
      defense mechanisms may function locally to limit Candida proliferation.

PMID- 9009329
TI  - Cloning and sequence analysis of the gbpC gene encoding a novel glucan-binding
      protein of Streptococcus mutans.
AB  - We have isolated dextran-aggregation-negative mutants of Streptococcus mutans
      following random mutagenesis with plasmid pVA891 clone banks. A chromosomal
      region responsible for this phenotype was characterized in one of the mutants. A
      2.2-kb fragment from the region was cloned in Escherichia coli and sequenced. A
      gene specifying a putative protein of 583 amino acid residues with a calculated
      molecular weight of 63,478 was identified. The amino acid sequence deduced from
      the gene exhibited no similarity to the previously identified S. mutans 74-kDa
      glucan-binding protein or to glucan-binding domains of glucosyltransferases but
      exhibited similarity to surface protein antigen (Spa)-family proteins from
      streptococci. Extract from an E. coli clone of the gene exhibited glucan-binding
      activity. Therefore, the gene encoded a novel glucan-binding protein.

PMID- 9009331
TI  - gamma-Glutamyltransferase from the outer cell envelope of Treponema denticola
      ATCC 35405.
AB  - The human oral spirochete Treponema denticola ATCC 35405 was shown to exhibit
      relatively high enzyme activity toward the gamma-glutamyl amide bond present in N
      gamma-L-glutamyl-4-nitroaniline. The enzyme responsible for this catalysis (gamma
      glutamyltransferase [GGT]; EC 2.3.2.2) was purified by means of fast protein
      liquid chromatography to two sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE)-pure forms from a mild (0.1%) Triton X-100 extract of
      washed cells. The GGT was studied primarily with regard to its hydrolytic
      activity by using N-gamma-L-glutamyl-4-nitroaniline as a substrate, although the
      GGT was shown to catalyze transpeptidation reactions. The high-molecular-mass
      form of the GGT gave a value of about 213 kDa by SDS-PAGE when heat treatment was
      omitted and one of 26 kDa after heat treatment; mass spectrometry gave a value of
      26.877. The larger form may represent an aggregate with nonprotein structures
      (possibly of a carbohydrate nature). The preliminary N-terminal sequence of the
      GGT is MKKPLIGITGSXLYETSQXXF. The enzyme was highly active on glutathione,
      transferring its Glu residue either to a water molecule or to the Gly-L-Leu
      dipeptide. The GGT stability was absolutely dependent on the presence of free
      thiol(s), while no evidence of metalloenzyme nature was obtained. The proposed
      location of the GGT in the outer cell envelope and its high activity on
      glutathione, a major nonprotein thiol present in virtually all cells, suggest
      that the GGT may play a role in the propagation of T. denticola within inflamed
      periodontal tissues.

PMID- 9009330
TI  - Induction of cytotoxic T-cell responses against culture filtrate antigens in
      Mycobacterium bovis bacillus Calmette-Guerin-infected mice.
AB  - CD8+ T cells are essential for protection against mycobacteria, as is clearly
      demonstrated by the fatal outcome of experimental infection of beta-2
      microglobulin knockout mice. However, the mechanisms and antigens (Ags) leading
      to CD8+ T-cell activation and regulation have been poorly characterized. Here we
      show that, upon immunization of major histocompatibility complex (MHC)-congenic
      mice with Mycobacterium bovis bacillus Calmette-Guerin (BCG), a cytotoxic
      response against BCG culture filtrate (CF) Ags (CFAgs) is induced in H-2b and H
      2bxd haplotypes but not in H-2d haplotype. This response is mediated by CD8+ T
      cells and absolutely requires the activation of CD4+ T cells and their secretion
      of interleukin 2. The lack of cytotoxic response in H-2d mice cannot be explained
      by impaired cytokine production or by a defect in Ag presentation by H-2d
      macrophages. Using the MHC class I mutant B6.C-H-2bm13 mouse strain, we
      demonstrate that cytotoxic T lymphocytes (CTLs) recognize CFAgs exclusively in
      association with D(b) molecules. These Ags are cross-reactive in mycobacteria,
      since BCG-induced CTLs also recognize macrophages pulsed with CF from
      Mycobacterium tuberculosis H37Rv and H37Ra and from two virulent strains of M.
      bovis. Moreover, immunization with Mycobacterium kansasii induces CTLs able to
      lyse macrophages pulsed with BCG CF. Finally, we have found that these Ags can be
      characterized as hydrophilic proteins, since they do not bind to phenyl-Sepharose
      CL-4B. Our results indicate that MHC-linked genes exert a profound influence on
      the generation of CD8+ CTLs following BCG vaccination.

PMID- 9009332
TI  - Effects of Mycobacterium tuberculosis on the bioelectric properties of the
      alveolar epithelium.
AB  - To investigate the hypothesis that Mycobacterium tuberculosis penetrates the
      alveolar epithelium by downregulating its barrier properties, we evaluated the
      interactions between M. tuberculosis and rat alveolar epithelial cell monolayers
      that are believed to share electrophysiologic properties of the human alveolar
      epithelium. Nonproteinaceous components of M. tuberculosis caused marked declines
      in electrical resistance and equivalent short-circuit current of the alveolar
      epithelial cell monolayers, indicating a reduction in the capacity to maintain
      tight intercellular junctions and to actively reabsorb sodium. M. tuberculosis
      elicited production of TNF-alpha mRNA and protein by alveolar epithelial cells,
      and the effects of recombinant TNF-alpha on the bioelectric properties of the
      alveolar epithelial paralleled those of M. tuberculosis. Furthermore, the effects
      of M. tuberculosis on alveolar epithelial resistance were abrogated by
      neutralizing anti-TNF-alpha antibodies. These results indicate that M.
      tuberculosis elicits production of TNF-alpha, which in turn reduces the
      bioelectric barrier properties of the alveolar epithelium. These findings provide
      insight into potential mechanisms by which M. tuberculosis establishes infection
      and disease in the lung.

PMID- 9009333
TI  - Cytokine and adhesion molecule expression in human monocytes and endothelial
      cells stimulated with bacterial heat shock proteins.
AB  - Bacterial heat shock proteins (HSPs) from Escherichia coli (GroES, GroEL, and
      DNAk) were tested for their ability to induce by themselves the expression and
      release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and
      granulocyte-monocyte colony-stimulating factor (GM-CSF) by human monocytes and GM
      CSF, IL-6, E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular
      cell adhesion molecule-1 (VCAM-1) by human umbilical vein endothelial cells
      (HUVEC). Our study demonstrated that treatment of monocytes with DNAk increased
      IL-6, TNF-alpha, and GM-CSF release in a dose-dependent manner. The same effect
      was elicited by GroEL but at a lower rate. Treatment of HUVEC cultures with DNAk
      and GroEL also increased GM-CSF, IL-6, E-selectin, ICAM-1, and VCAM-1 release in
      a dose-dependent fashion. In any case, the greatest release was obtained by using
      DNAk and GroEL at a concentration of 1 microg/ml. DNAk and GroEL were also able
      to up-regulate the surface expression of E-selectin, ICAM-1, and VCAM-1. As
      detected by reverse transcription-PCR analysis, DNAk and GroEL also increased the
      steady-state levels of cytokines and adhesion molecules in human monocytes and
      endothelial cells. In our study GroES showed a significant activity only on the
      release, surface expression, and mRNA transcription of E-selectin. Adhesion
      molecule expression seems to be a direct effect of HSPs and not via cytokines.
      Furthermore, these effects are due to HSPs properties because they are inhibited
      by specific monoclonal antibodies. These findings support the potential role of
      HSPs in modulating cell interactions during immunological and inflammatory
      responses.

PMID- 9009334
TI  - Role of SefA subunit protein of SEF14 fimbriae in the pathogenesis of Salmonella
      enterica serovar Enteritidis.
AB  - In this study, the role of the SefA subunit protein of SEF14 fimbriae in the
      pathogenesis of Salmonella enterica serovar Enteritidis was investigated. This
      was accomplished by mutating the sefA gene in the chromosome of two strains of S.
      enterica serovar Enteritidis by allelic exchange with a copy that has been
      inactivated by interruption with a nonpolar kanamycin resistance (aphA-3)
      cassette. The effect of this mutation on the ability of the S. enterica serovar
      Enteritidis strains to colonize the intestinal epithelium and to invade other
      tissues was assessed in BALB/c mice and in vitro by adherence and invasion of
      HeLa cells. Our results show that an avirulent S. enterica serovar Enteritidis
      vaccine strain, 11RX (no somatic antigen; flagellum antigen phase 1, g,m;
      flagellum antigen phase 2, -), colonized better and persisted longer in the
      Peyer's patches of these mice than did its SefA-deficient counterpart. However,
      no such difference was observed between a highly virulent S. enterica serovar
      Enteritidis strain, 7314 (somatic antigen, O1, O9, O12; flagellum antigen phase
      1, g,m; flagellum antigen phase 2 [1,7]), and its SefA-deficient isogenic mutant.
      These findings were correlated with in vitro adherence and invasion of HeLa
      cells. Furthermore, we could not demonstrate a role for SefA in the virulence of
      S. enterica serovar Enteritidis as assessed by 50% lethal dose determinations.
      The implications of these findings are discussed.

PMID- 9009335
TI  - Reactivity patterns and epitope specificities of anti-Cryptococcus neoformans
      monoclonal antibodies by enzyme-linked immunosorbent assay and dot enzyme assay.
AB  - Cryptococcus neoformans glucuronoxylomannans (GXM) are capsular polysaccharides
      important for virulence in cryptococcosis. This study used dot enzyme assays
      (DEA) and enzyme-linked immunosorbent assays (ELISA) to determine the reactivity
      patterns of 21 murine monoclonal antibodies (MAbs) with structurally defined GXMs
      from five serotypes. The MAbs were categorized into eight groups on the basis of
      DEA and five groups on the basis of ELISA. MAbs 302, 339, and 439 were studied
      extensively for their binding to various native and chemically modified GXMs.
      Quantitative variation in the inhibitory effects of GXMs on the binding of MAbs
      302, 339, and 439 were observed by competitive ELISA. O-Deacetylation of serotype
      A, B, and D GXM resulted in the complete loss of their inhibitory properties.
      Carboxyl group reduction of GXMs from serotypes A and D resulted in a significant
      decrease of inhibitory activity for MAb. Xylomannans and methyl glycosides
      exhibited no detectable inhibitory activity on MAb binding to GXM. The results
      indicate (i) the existence of five to eight MAb-defined distinct epitopes in C.
      neoformans GXM that can elicit antibody responses, (ii) MAb detection of
      antigenic variation within GXMs assigned to a particular serotype, (iii) good
      correspondence between the patterns of MAb reactivities and polyclonal rabbit
      factor sera, (iv) good agreement between MAb molecular structure and serotype
      reactivity, and (v) a dependence of the serotype reactivity profile for a given
      MAb on the technique used to measure binding.

PMID- 9009336
TI  - Invasion of Vero cells and induction of apoptosis in macrophages by pathogenic
      Leptospira interrogans are correlated with virulence.
AB  - Interactions of virulent Leptospira interrogans serovar icterohaemorrhagiae
      strain Verdun with Vero cells (African green monkey kidney fibroblasts) and a
      monocyte-macrophage-like cell line (J774A.1) were assayed by a double
      fluorescence immunolabelling method. Infectivity profiles were investigated
      according to (i) the duration of contact between leptospires and eukaryotic cells
      and (ii) the number of in vitro passages after primary isolation from lethally
      infected guinea pigs. Comparative experiments were conducted with the
      corresponding high-passage avirulent variant and the saprophytic leptospire
      Leptospira biflexa Patoc I. In Vero cells, virulent leptospires were quickly
      internalized from 20 min postinfection, whereas avirulent and saprophytic strains
      remained extracellularly located. In addition, the virulent strain demonstrated
      an ability to actively invade the monocyte-macrophage-like J774A.1 cells during
      the early stages of contact and to induce programmed cell death, as shown by the
      detection of oligonucleosomes in a quantitative sandwich enzyme immunoassay. In
      both cellular systems, subsequent in vitro subcultures demonstrated a progressive
      decrease of the invasiveness, pointing out the necessity of using primocultures
      of Leptospira for virulence studies. Invasiveness of virulent leptospires was
      significantly inhibited with monodansylcadaverine, indicating that
      internalization was dependent on receptor-mediated endocytosis. Invasion of
      epithelial cells and induction of apoptosis in macrophages may be related to the
      pathogenicity of Leptospira, and both could contribute to its ability to survive
      in the host and to escape from the immune response.

PMID- 9009337
TI  - In situ characterization of inflammatory responses in the rectal mucosae of
      patients with shigellosis.
AB  - Shigella species cause bacillary dysentery in humans by invading epithelial cells
      of the colonic mucosa leading to colonic epithelial cell destruction and
      inflammation. For further analysis of local gut inflammation, morphological
      changes and the potential involvement of mediators in regulatory mechanisms of
      cell activation and cell proliferation were studied immunohistochemically in
      rectal mucosal biopsies taken from patients during the acute phase of shigellosis
      and at convalescence. Rectal biopsies from 25 Shigella dysenteriae-1 and 10
      Shigella flexneri-infected patients and from 40 controls were studied. The
      frequencies of proliferative cells (Ki67-positive cells), p53-immunostaining
      cells, and cells coexpressing Ki67 with CD3 or with p53 were analyzed.
      Immunostaining for the inducible nitric oxide synthase (iNOS) and the endothelial
      NOS was assessed. In addition, the frequencies of apoptotic cells and CD68+ cells
      that engulf apoptotic cells were assessed. By morphological grading, 20% of the
      patients had advanced inflammation (grade 3) in the acute phase; mild
      inflammation (grade 1) was seen in 37% of the patients at convalescence as well
      as in 10% of the controls. The findings in the present study suggest that in the
      acute phase of shigellosis inflammation is characterized by increased cell
      turnover in the lamina propria (LP) and the epithelium, increased iNOS expression
      in the surface epithelium, and apoptosis, which seems to be associated with LP
      macrophages. The findings also suggest that neither p53 nor iNOS are important
      factors for the induction of apoptosis in shigellosis. Expression of p53 may be
      related to early cell activation in crypt epithelium. Moreover, there is an
      indication of an active, low-level inflammatory process at convalescence. The
      results thus indicate that Shigella-induced inflammation is associated with a
      complex series of cellular reactions in the rectal gut mucosa which persist long
      after clinical symptoms have resolved.

PMID- 9009338
TI  - Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by
      sialic acid-containing oligosaccharides.
AB  - Helicobacterpylori, the ulcer pathogen residing in the human stomach, binds to
      epithelial cells of the gastric antrum. We have examined binding of 13 bacterial
      isolates to epithelial cell lines by use of a sensitive microtiter plate method
      in which measurement of bacterial urease activity provides the means for
      quantitation of bound organisms. Several established human gastrointestinal
      carcinoma cell lines grown as monolayers were compared for suitability in these
      assays, and the duodenum-derived cell line HuTu-80 was selected for testing
      bacterial binding inhibitors. When bacteria are pretreated with oligosaccharides,
      glycoproteins, and glycolipids, a complex picture of bacterial-epithelial
      adherence specificities emerges. Among the monovalent inhibitors tested, 3'
      sialyllactose (NeuAc alpha2-3Gal beta1-4Glc; 3'SL) was the most active
      oligosaccharide, inhibiting adherence for recent clinical isolates of H. pylori
      with a millimolar 50% inhibitory concentration (IC50). Its alpha2-6 isomer (6'SL)
      was less active. Most of the recent clinical isolates examined were inhibited by
      sialyllactose, whereas long-passaged isolates were insensitive. Among the long
      passaged bacterial strains whose binding was not inhibited by 3'SL was the strain
      ATCC 43504, also known as NCTC 11637 and CCUG 17874, in which the proposed
      sialyllactose adhesin was recently reported to lack surface expression (P. G.
      O'Toole, L. Janzon, P. Doig, J. Huang, M. Kostrzynska, and T. H. Trust, J.
      Bacteriol. 177:6049-6057, 1995). Pretreatment of the epithelial monolayer with
      neuraminidase reduced the extent of binding by those bacteria that are sensitive
      to inhibition by 3'SL. Other potent inhibitors of bacterial binding are the
      glycoproteins alpha1-acid glycoprotein, fetuin, porcine gastric and bovine
      submaxillary mucins, and the glycolipid sulfatide, all of which present
      multivalent sialylated and/or sulfated galactosyl residues under the conditions
      of the binding assay. Consistent with this pattern, a multivalent
      neoglycoconjugate containing 20 mol of 3'SL per mol of human serum albumin
      inhibited bacterial binding with micromolar IC50. The H. pylori isolate most
      sensitive to inhibition by 3'SL was least sensitive to inhibition by sulfatide,
      gastric mucin, and other sulfated oligosaccharides. Bacteria that have been
      allowed to bind epithelial cells are also effectively detached by 3'SL. These
      results describe a heterogeneous adherence repertoire for these bacteria, but
      they also confirm the critical role of the 3'SL structure on human gastric
      epithelial cells as an adherence ligand for recent isolates of H. pylori.

PMID- 9009339
TI  - Characterization of the Chlamydia trachomatis vacuole and its interaction with
      the host endocytic pathway in HeLa cells.
AB  - Chlamydia trachomatis, an obligate intracellular parasite and a major human
      pathogen, invades eukaryotic host cells and replicates within a membrane-bound
      compartment (termed the vacuole or inclusion) in the cytoplasm of the host cell.
      In this report, we describe in detail the characteristics of the vacuole
      throughout the chlamydial life cycle in terms of the endocytic pathway, as
      determined by epifluorescent and confocal immunofluorescence microscopy. By
      indirect immunofluorescence, the transferrin receptor (TfR), a component of early
      endosomes, and the cation-independent mannose-6-phosphate receptor (CI-M6PR), a
      component of late endosomes, were found in close association with the chlamydial
      vacuole as early as 4 h postinfection (hpi) and as late as 20 hpi. Fluorescein
      isothiocyanate (FITC)-labeled Tf was also found to colocalize with the vacuole at
      4, 12, and 20 hpi, indicating that exogenously added ligands can be transported
      to the region of the vacuole. Antibodies to several different lysosomal proteins
      failed to label the chlamydial vacuole at any time point during the life cycle.
      Indirect immunofluorescence of cells infected with chlamydiae stained with an
      antibody to the trans-Golgi network (TGN) protein TGN38 demonstrated that in
      infected cells, the integrity and structure of the TGN was altered. The rates of
      Tf recycling in infected and uninfected cells were compared by fluorescence
      microscopy and quantitated with 125I-Tf. While the rate of FITC-Tf recycling from
      endocytic compartments in chlamydia-infected cells did not appear different from
      that of uninfected cells, a small pool of FITC-Tf that had accumulated adjacent
      to the chlamydial vacuole recycled at a slower rate. Quantitation of Tf recycling
      with 125I-Tf showed that Tf was recycled more slowly in infected cells than in
      uninfected cells. The altered distribution of several endocytic pathway markers
      and the slowed Tf recycling are consistent with the hypothesis that the
      chlamydial vacuole interacts with the endocytic pathway of the host. These
      results furthermore suggest that the chlamydial vacuole does not correspond to a
      canonical endocytic compartment but that it is a unique and dynamic organelle
      that shares several characteristics with recycling endosomes of the host cell.
      Interactions with the early and/or late endosomal compartments, in addition to
      the Golgi apparatus, may provide a source of membrane or nutrients for the
      replicating organisms.

PMID- 9009340
TI  - Mycobacterium marinum causes both long-term subclinical infection and acute
      disease in the leopard frog (Rana pipiens).
AB  - Mycobacterium marinum grows at an optimal temperature of 33 degrees C, far lower
      than that for M. tuberculosis. Consequently, M. marinum infection of mammals is
      restricted largely to the cooler surfaces of the body, such as the extremities,
      but it causes a systemic infection in a large number of poikilothermic animals.
      Here, we describe a laboratory animal model for M. marinum disease in the leopard
      frog (Rana pipiens), a natural host species. M. marinum causes a chronic
      granulomatous, nonlethal disease in immunocompetent frogs. Immunosuppression of
      the frogs with hydrocortisone results in an acute, fulminant, lethal disease.
      This animal model, in which a spectrum of tuberculosis-like disease can be
      produced, will be useful for the dissection of the genetic basis of mycobacterial
      pathogenesis.

PMID- 9009341
TI  - Secretion of Shigella flexneri Ipa invasins on contact with epithelial cells and
      subsequent entry of the bacterium into cells are growth stage dependent.
AB  - Upon contact with the surface of epithelial cells, Shigella flexneri secretes Ipa
      proteins through the Mxi-Spa type III secretion apparatus. Among the Ipa
      proteins, IpaB and IpaC form a soluble complex in the bacterial supernatant which
      appears to be sufficient to initiate the cellular rearrangements necessary to
      achieve bacterial entry. Here, we provide the first evidence that efficiency of
      bacterial entry into cells depends on the stage of bacterial growth. Bacteria in
      the early phase of exponential growth are six times more invasive than those in
      the stationary phase. The entry efficiency of the bacteria present on the cell
      surface appears to correlate with the percentage of those that are able to
      secrete their invasins. This suggests that the capacity to activate the Mxi-Spa
      apparatus is a major factor in the regulation of bacterial entry efficiency.
      Consistent with these observations, we have further shown that bacteria which
      have reached the stage of division secrete Ipa proteins more often than those
      that have not. Also, initial secretion occurs essentially in the area of the
      septation furrow. The Ipa proteins, secreted in the vicinity of the septation
      furrow, seem to initiate the early stages of reorganization of the host cell
      cytoskeleton.

PMID- 9009342
TI  - Proteophosphoglycan secreted by Leishmania mexicana amastigotes causes vacuole
      formation in macrophages.
AB  - The amastigote form of Leishmania mexicana parasites colonizes macrophage
      phagolysosomes and induces the enlargement of these compartments to form huge
      parasitophorous vacuoles. We report here that a purified secreted amastigote
      product, proteophosphoglycan, is a macromolecule which causes vacuolization of
      peritoneal macrophages in vitro. Secretion of this glycoconjugate by
      intracellular parasites may contribute to the expansion of phagolysosomal
      compartments in infected cells.

PMID- 9009343
TI  - IpaB, a Shigella flexneri invasin, colocalizes with interleukin-1 beta-converting
      enzyme in the cytoplasm of macrophages.
AB  - Shigellae are the most prevalent etiological agents of dysentery. A crucial step
      in shigella pathogenesis is the induction of macrophage apoptosis. The invasion
      plasmid antigen B (IpaB) is necessary and sufficient to induce macrophage
      programmed cell death. IpaB activates apoptosis by binding to interleukin-1 beta
      (IL-1 beta)-converting enzyme (ICE) or a highly homologous protease. Here, we
      show that IpaB is disseminated throughout the cytoplasm of shigella-infected
      macrophages as detected by both immunofluorescence and immunoelectron microscopy.
      The cytoplasmic distribution of IpaB requires phagosome escape, and it is
      specific to IpaB, since lipopolysaccharide, used here as a bacterial marker,
      remains closely associated with the bacteria. In double-labeling experiments, we
      show that IpaB and ICE colocalize in the cytoplasm of the macrophage, suggesting
      that soon after secretion, IpaB binds to ICE to initiate apoptosis and to promote
      the cleavage of IL-1 beta.

PMID- 9009345
TI  - Protection against infection in mice vaccinated with a Brucella abortus mutant.
AB  - This study determines whether a genetically engineered mutant of Brucella
      abortus, strain M-1, possesses differences in protective properties compared to
      the parental strain, vaccine S19. M-1 is a mutant unable to express BP26, a
      periplasmic protein with potential use in diagnosis. Mice vaccinated with S19
      developed antibodies against BP26, while those vaccinated with M-1 did not.
      However, mice vaccinated with S19 or M-1 were similarly protected against
      challenge with pathogenic strain 2308, suggesting that the lack of BP26 does not
      affect the induction of the protective immune response exerted by S19. These and
      previous results showing that bacterial invasion and growth or replication in
      mouse spleens were indistinguishable between strains M-1 and S19 could indicate
      that the mutant is an attenuated strain which maintains the same protective
      properties as S19.

PMID- 9009346
TI  - Production of monoclonal antibodies to the non-membrane-damaging cytotoxin
      (NMDCY) purified from Vibrio cholerae O26 and distribution of NMDCY among strains
      of Vibrio cholerae and other enteric bacteria determined by monoclonal-polyclonal
      sandwich enzyme-linked immunosorbent assay.
AB  - The distribution of a newly described secretogenic non-membrane-damaging
      cytotoxin (NMDCY) among strains of Vibrio cholerae and other enteric bacteria was
      determined. To accomplish this, monoclonal antibodies against NMDCY were prepared
      and a sandwich monoclonal-polyclonal enzyme-linked immunosorbent assay (ELISA)
      was developed. By the sandwich ELISA, it was determined that 55.6% of the 412
      strains of V. cholerae examined produced NMDCY at varying concentrations while
      76, 37.9, and 15.6% of the clinical strains of Vibrio parahaemolyticus, Aeromonas
      spp., and Shigella spp., respectively, produced NMDCY. Because of its
      enterotoxigenic potential and based on its widespread distribution among strains
      of V. cholerae, we believe that NMDCY may constitute an important virulence
      determinant in the cascade of events which enable the organism to precipitate the
      disease.

PMID- 9009344
TI  - Identification of a frameshift mutation resulting in premature termination and
      loss of cell wall anchoring of the PAc antigen of Streptococcus mutans GS-5.
AB  - Most strains of Streptococcus mutans possess a 190-kDa protein antigen (PAc) on
      their cell surfaces, while strain GS-5 produces extracellularly a 155-kDa PAc
      protein. The pac gene of strain GS-5 consists of 3,477 bp and codes for a protein
      of 1,158 amino acids. One insertion of an adenine into the 3,469th, 3,470th, or
      3,471st position from the start codon results in a frameshift mutation at codon
      1157 with subsequent termination after 3 additional codons.

PMID- 9009347
TI  - Decreased intracellular survival of an fkpA mutant of Salmonella typhimurium
      Copenhagen.
AB  - The fkpA gene of Salmonella typhimurium encodes a protein similar to the
      macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and
      Chlamydia trachomatis. Because Mip proteins enhance the ability of these
      intracellular pathogens to survive within macrophages and epithelial cells, we
      tested whether the product of the fkpA gene would have the same effect on the
      intracellular growth of a virulent strain of S. typhimurium. By a series of P22
      transductions, the fkpA gene of S. typhimurium Copenhagen was replaced with the
      inactive fkpA1::omega-Cm gene from Escherichia coli, creating the mutant S.
      typhimurium KY32H1. The Copenhagen and KY32H1 strains were equally able to enter
      Caco-2 cells (an epithelial cell line) and J774.A1 cells (a macrophage-like cell
      line). However, compared to the parent, the fkpA mutant survived less well in
      both types of cells during the first 6 h after infection. The number of viable
      intracellular S. typhimurium Copenhagen bacteria remained constant 6 h after
      infection of Caco-2 cells, but the viability of S. typhimurium KY32H1 decreased
      significantly by 4 h postinfection. The fkpA mutant also exhibited a reduced
      ability to survive intracellularly in J774.A1 cells as little as 2 h
      postinfection. Complementation of the fkpA mutation by a plasmid-borne wild-type
      fkpA gene from E. coli restored the ability of S. typhimurium KY32H1 to grow
      normally in J774.A1 cells. Thus, expression of the mip-like fkpA gene confers on
      S. typhimurium Copenhagen properties analogous to those mediated by the Mip
      proteins in other intracellular pathogens, suggesting that this mechanism may
      play a role in the virulence and/or intracellular growth of numerous bacteria.

PMID- 9009348
TI  - Similarities and disparities between core-specific and O-side-chain-specific
      antilipopolysaccharide monoclonal antibodies in models of endotoxemia and
      bacteremia in mice.
AB  - We have previously described cross-reactive antilipopolysaccharide (anti-LPS), or
      anti-endotoxin, monoclonal antibodies (MAbs) which provide cross-protection in
      several systems of endotoxin bioactivity. The protective effects of the murine
      cross-reactive MAb WN1 222-5 (immunoglobulin G2a(kappa) [IgG/2a(kappa)]) and of
      its chimerized version, SDZ 219-800 [human IgG1(kappa)], have now been evaluated
      in lethality models against LPS from three different serotypes and in bacterial
      infection models. We confirmed the protective activity of the two MAbs in D
      galactosamine-sensitized mice challenged with LPS of other E. coli serotypes
      (O18, O127, and O111). The protective effect correlated with the suppression of
      tumor necrosis factor formation. Furthermore, WN1 222-5 enhanced bacterial
      clearance of intravenously administered E. coli O111 bacteria, thus protecting
      mice from death. However, the MAbs were unable to provide protection in a
      peritonitis model (intraperitoneal inoculation). Our study, therefore, shows that
      LPS cross-reactive antibodies are capable of mediating cross-protection against
      LPS and bacteria but that the selected models have a clear influence on the
      results.

PMID- 9009349
TI  - Porphyromonas gingivalis fimbria-stimulated bone resorption is inhibited through
      binding of the fimbriae to fibronectin.
AB  - Our most recent study demonstrated that fibronectin is one of the Porphyromonas
      gingivalis fimbria-binding proteins. In this present study, we demonstrate with
      mouse embryonic calvarial cells that P. gingivalis fimbria-stimulated bone
      resorption is inhibited by human fibronectin. The fibronectin inhibition was dose
      and culture time dependent and was completely neutralized by antifibronectin
      antibody. The inhibitory action of fibronectin depended on fimbrial interaction
      with the heparin-binding and cell-attachment domains in the fibronectin
      structure.

PMID- 9009350
TI  - Expression of aerobactin genes by Shigella flexneri during extracellular and
      intracellular growth.
AB  - The expression of the Shigella flexneri chromosomal aerobactin genes during
      growth of the bacterium within tissue culture cells was assayed. During
      intracellular growth, aerobactin promoter activity was repressed relative to the
      level observed in bacteria grown extracellularly, even when the bacteria had been
      starved for iron prior to infection. Similarly, the level of one of the proteins
      encoded by this operon, the aerobactin outer membrane receptor, Iut, was reduced
      in the intracellular environment. These studies indicate that the aerobactin
      system is not highly expressed by bacteria within host cells, suggesting that
      siderophore-independent iron acquisition systems can provide essential iron
      during intracellular multiplication.

PMID- 9009351
TI  - Characterization of the diversity and the transferrin-binding domain of
      gonococcal transferrin-binding protein 2.
AB  - The molecular weight heterogeneities of Tbp1 and Tbp2 among a panel of 45
      gonococcal isolates were assessed. The tbpB genes from four of these strains were
      sequenced to characterize the Tbp2 sequence diversity among gonococci. By
      expressing truncated versions of gonococcal Tbp2, we delimited the extent of Tbp2
      necessary for transferrin binding in a Western blot.

PMID- 9009352
TI  - Avirulence of Candida albicans FAS2 mutants in a mouse model of systemic
      candidiasis.
AB  - Disruption of both alleles of the Candida albicans FAS2 gene abolishes the
      ability of the organism to establish infection in a murine model of systemic
      candidiasis. Within 72 h all mice inoculated with 10(6) CFU of the parental C.
      albicans strain had died. In contrast, all animals inoculated with the mutant
      strain CFD2 survived for the course of the experiment (21 days). Animals infected
      with either mutant strain CFD1 or CFD3, in which only one FAS2 allele was
      disrupted, also succumbed to infection, but mortality was not observed until 4
      days postinfection and survivors remained for up to 20 days postinfection. The
      results demonstrate that FAS2 is required for successful C. albicans infection.

PMID- 9009353
TI  - Reduced virulence of Candida albicans MKC1 mutants: a role for mitogen-activated
      protein kinase in pathogenesis.
AB  - Deletion of the Candida albicans mitogen-activated protein kinase MKC1 gene gave
      rise to viable cells whose cell integrity was affected (F. Navarro-Garcia, M.
      Sanchez, J. Pla, and C. Nombela, Mol. Cell. Biol. 15:2197-2206, 1995). In an
      experimental infection system using a murine model, the C. albicans mkc1
      delta/mkc1 delta strain was found to be less pathogenic than the parental strain,
      as show the different time of survival, percentage of mortality, fungal load in
      the most representative organs, and histological analysis. This is the first
      study that shows the involvement of the cell integrity pathway in the
      pathogenicity of a dimorphic fungus.

PMID- 9009354
TI  - Development of a murine model of chronic Salmonella infection.
AB  - The invasive disease caused by Salmonella typhimurium in mice resembles the acute
      phase of human typhoid fever caused by Salmonella typhi, and experimental murine
      salmonellosis is a widely used experimental model for systemic salmonellosis. In
      this paper we demonstrate that murine S. typhimurium infection can also be used
      to model the development of the chronic carrier state that develops in humans
      after infection with S. typhi. We describe a virulent variant of S. typhimurium
      that has decreased expression of AgfA fibers under all environmental conditions
      studied and that causes a chronic carrier state in BALB/c mice after peroral
      inoculation. The chronic carrier state is associated with persistence of bacteria
      in the small intestine, spleen, and liver, and chronic infection continues
      despite the development of protective immunity to challenge with virulent
      Salmonella.

PMID- 9009355
TI  - Coccoid and spiral Helicobacter pylori differ in their abilities to adhere to
      gastric epithelial cells and induce interleukin-8 secretion.
AB  - Helicobacter pylori exists as an actively dividing spiral form and a
      nonculturable, but viable, metabolizing coccoid form. Both forms are present in
      the stomach, but their relative pathophysiologic significances are unknown. Here
      we show that the coccoid form of H. pylori, in contrast to the spiral form, binds
      poorly to gastric epithelial cells and induces little, if any, interleukin-8
      secretion by these cells.

PMID- 9009356
TI  - Adhesive factor/rabbit 2, a new fimbrial adhesin and a virulence factor from
      Escherichia coli O103, a serogroup enteropathogenic for rabbits.
AB  - Enteropathogenic Escherichia coli-like E. coli strains belonging to serovar
      O103:K-:H2 and rhamnose-negative biotypes are highly pathogenic diarrhea-inducing
      strains for weaned European rabbits. We describe here the cloning and sequencing
      of the major subunit gene of a new fimbrial adhesin, adhesive factor/rabbit 2
      (AF/R2), which confers on these strains the ability to attach to rabbit
      enterocytes and to HeLa cells in a diffuse manner and which is associated with in
      vivo virulence. The chromosomal operon that encodes functional AF/R2 has been
      cloned from strain B10. The major subunit gene afr2G, as well as an adjacent open
      reading frame, afr2H, has been sequenced. The Afr2G protein shows homologies with
      FaeG and ClpG, which are the respective major subunits of fimbrial adhesin K88
      (F4) and afimbrial adhesin CS31A. Plasmid carrying the operon transcomplements an
      AF/R2-negative TnphoA mutant for its ability to express AF/R2. As a whole, AF/R2
      is a new member of the E. coli K88 adhesin family which is associated with
      virulence and which may serve in the design of vaccines.

PMID- 9009357
TI  - Fundus changes in patients with the mitochondrial DNA point mutation at position
      3243.
AB  - The A3243G transition in the mitochondrial DNA is commonly associated with the
      syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like
      episodes (MELAS). Previously, atypical pigmentary retinopathy has been described
      in patients with this syndrome and in patients with other phenotypes of the same
      mitochondrial defect. Maternally inherited diabetes mellitus and deafness has
      been recognized as a distinct clinical presentation of the mitochondrial point
      mutation at position 3243, and recently a pattern dystrophy has been identified
      as a characteristic ocular abnormality in these patients. The finding of a
      macular pattern dystrophy in patients with diabetes should therefore lead to
      screening for this aberrant mitochondrial genome.

PMID- 9009359
TI  - Keratoplasty a chaud in severe keratitis.
AB  - We have analysed the results of 19 penetrating keratoplasties a chaud performed
      in 18 patients presenting with imminent perforation or perforated corneas.
      Infectious disease was eradicated in all cases except in those patients suffering
      from acanthamoeba keratitis. Secondary bacterial infection was observed in three
      grafts. Six eyes required a second keratoplasty; two of them were regrafted
      several times but finally enucleated. Six patients (32%) reached a visual acuity
      between 10/10 and 5/10, four patients (21%) between 5/10 and 1/10 and nine
      patients (47%) less than 1/10.

PMID- 9009360
TI  - Therapy-resistant corneal ulcer in a six-year old patient.
AB  - Throughout this case emerges the importance of a thorough ophthalmological
      examination of children who have suffered an eye trauma. A double eversion of the
      upper eyelid under narcosis may be necessary to detect the presence of a foreign
      body.

PMID- 9009358
TI  - Immunopathogenesis of vernal keratoconjunctivitis.
AB  - We have analyzed the in situ distribution of immune cells in the conjunctival
      biopsy specimens obtained from patients with active vernal keratoconjunctivitis
      (VKC). We used immunohistochemical techniques and a panel of monoclonal and
      polyclonal antibodies. Our data point to a complex immunopathogenesis of the
      disease. Distinct components involved in IgE-mediated immune mechanisms, as well
      as humoral and cell mediated immune mechanisms were detected in the conjunctival
      tissues. In addition, we investigated the presence and distribution of adhesion
      molecules. In the normal conjunctiva, intercellular adhesion molecule-1 (ICAM-1)
      was expressed only on the vascular endothelium, lymphocyte function associated
      antigen-1 (LFA-1) and intercellular adhesion molecule-3 (ICAM-3) on epithelial
      and stromal mononuclear cells, and very late activation antigen-4 (VLA-4) on a
      few stromal mononuclear cells. Endothelial leukocyte adhesion molecule-1 (ELAM-1)
      and vascular cell adhesion molecule-1 (VCAM-1) expression was not detected. In
      VKC a marked increase of all these antigens was observed. Strong ICAM-1
      expression was induced on the basal epithelial cells, and vascular endothelium.
      Furthermore, about 30% of the stromal mononuclear cells expressed ICAM-1. LFA-1
      and ICAM-3 were expressed on the majority of infiltrating mononuclear cells. VLA
      4 expression was noted on about 25% of the stromal mononuclear cells. ELAM-1 and
      VCAM-1 were induced on the vascular endothelial cells. Our results suggests that
      increased expression of adhesion molecules in VKC promotes the recruitment of
      inflammatory cells through blood vessels and the cell interaction between
      lymphocytes and antigen presenting cells, among lymphocytes, as well as between
      lymphocytes and epithelial cells.

PMID- 9009361
TI  - Diagnosis of a masked bilateral congenital superior oblique palsy.
AB  - Some patients in whom the diagnosis of a purely unilateral congenital superior
      oblique palsy was made, developed signs of a palsy in the fellow eye after
      surgery was done. A review of all diagnostic tests used in discovering the
      presence of a masked bilateral superior oblique palsy is given. The usefulness of
      the occlusion-test, which is often forgotten, is illustrated.

PMID- 9009362
TI  - A modified Jones tube.
AB  - A modified Jones tube was designed and this new model was implanted in 33 cases
      with severe canalicular or common canalicular obstruction. The tube, with a
      length of 24 mm, has a 130 degree angulation in the middle. The insertion of this
      Jones tube can be performed with or without dacryocystorhinostomy. Despite some
      problems in the beginning, the results seem to be very promising, with a 80%
      success rate.

PMID- 9009364
TI  - Ocular manifestations in Delleman syndrome (Oculocerebrocutaneous syndrome, OCC
      syndrome) and encephalocraniocutaneous lipomatosis (ECCL). Report of three cases.
AB  - The authors present two patients with Delleman syndrome and one in with possible
      ECCL. Two boys with Delleman syndrome showed characteristic dysmorphic features
      with cerebral, ocular and skin malformations. The ocular anomalies consisted of
      eyelid coloboma, microphthalmia, iris coloboma and epibulbar lypodermoids. A
      third boy with possible ECCL syndrome had limbal lypodermoids, ectopia pupillae
      and aberrant iris tissue in the right eye. He showed an ipsilateral focal dermal
      hypoplastic defect within an area of alopecia of the scalp.

PMID- 9009363
TI  - Modified phacotrabeculectomy with Crozafon punch.
AB  - We retrospectively evaluated the results of combined phacoemulsification and
      trabeculectomy by analyzing 22 consecutive operations. A "Crozafon punch" was
      used to perform the trabeculectomy through the sclerocorneal tunnel. The mean
      follow-up period was 6 months. Visual acuity of 0.5 or better was achieved in 18
      eyes (82%). Intraocular pressure control was achieved in 18 eyes without
      medication, 4 eyes required a beta-blocking agent. The complication rate was low.

PMID- 9009365
TI  - Tubulo-interstitial nephritis-uveitis (TINU)-syndrome with posterior uveitis.
AB  - A case of TINU-syndrome with complications in the posterior segment is reported.
      A 15-year old boy presented, eight months after an acute tubulo-interstitial
      nephritis, a bilateral anterior uveitis, followed by an unilateral posterior
      uveitis with papillitis. The treatment with oral and topical corticosteroids was
      successful.

PMID- 9009366
TI  - Premacular fibrosis in juvenile Coats' disease with spontaneous peeling after
      photocoagulation of the congenital vascular anomalies.
AB  - We studied two cases of juvenile coats' disease with visual loss at presentation
      due to premacular fibrosis. The retinal area with altered vascularization was
      photocoagulated with the Argon green laser. The membrane retracted in a matter of
      a few months resulting in improved visual acuity. Afterwards the membrane
      completely peeled and was seen as a floater attached to the posterior hyaloid.
      Peeling of premacular fibrosis in juvenile's Coats disease may be observed after
      photocoagulation treatment. It is suggested that induced posterior vitreal
      detachment was associated with peeling of the premacular fibrosis.

PMID- 9009367
TI  - Secondary closure of posterior continuous circular capsulorhexis.
AB  - We examined the hypothesis that removing the center of the posterior capsule
      would reduce the risk for posterior opacification (PCO). We considered the
      prevalence of post-operative complications after PCCC like retinal detachment and
      cystoid macular edema, as found after Nd-YAG laser capsulotomy.

PMID- 9009368
TI  - Evaluation of echography in orbital disease.
AB  - A report is given on a series of 34 patients with suspicion of orbital disease,
      who were examined by standardized echography. We compared the efficacy of
      standardized echography in orbital disease with CT and NMR and concluded that SE
      has not become less important since the introduction of CT and NMR. It can
      supplement CT and NMR and remains a valuable and indispensible guide for the
      management of orbital disease.

PMID- 9009369
TI  - Postoperative instillation of 0.04% mitomycin C in the treatment of primary
      pterygium in Zaire.
AB  - PURPOSE: to investigate, in the first report in Central Africa, the influence of
      tropical Mitomycin C on the recurrence rate and on the complications after
      surgical treatment for primary pterygium. METHODS: Sixty-six patients with
      primary pterygia underwent excision of the lesion, leaving the sclera bare.
      Patients were randomized in two groups: in one group (36 eyes in 33 patients)
      0.04% mitomycin C eye drops were used four times daily during two weeks or longer
      after surgery, the other group (41 eyes in 33 patients) underwent only surgery.
      The mean follow-up period was 6 months (range, one to 24 months). RESULTS: seven
      (19.4%) pterygia recurred in the group of eyes treated with topical 0.04%
      mitomycin C and 11 (26.8%) in the group of eyes treated without this drug. This
      difference was not significant (p > 0.05). Complications were observed in two
      (5.6%) eyes in group 1 and included conjunctival granuloma (one eye) and
      transient ocular hypertension. In group 2, complications were noted in four eyes
      (9.8%) and included conjunctival granulomas (three eyes) and symblepharon (one
      eye). Ocular hypertension could be due to instillation of mitomycin C. No group
      had significantly more complications. CONCLUSION: primary excision of pterygium
      with postoperative instillation of 0.04% mitomycin C had a higher rate of
      occurrence in this study than previously reported in Japan, in the USA and
      Europe.

PMID- 9009370
TI  - Efficacy of tissue plasminogen activator (t-PA) in subretinal hemorrhage removal.
AB  - t-PA can be used intra-operatively to liquify a large and elevated submacular
      blood clot and to facilitate the aspiration through a small retinotomy. In 15
      consecutive patients we operated in this way, we noticed that an intra-operative
      subretinal injection of t-PA was never able to dissolve the blood clot
      completely. Therefore it was necessary to perform a large retinotomy in large
      hemorrhages.

PMID- 9009371
TI  - Implantation of posterior chamber lenses of more than 30 dptr.
AB  - Posterior chamber lenses of more than 30 dptr. are supposed to correct
      preexisting high hyperopia. With high diopters, however, problems emerge which
      are not to be found in eyes requiring lower lens powers. These problems are
      neurosensory disorders, residual accommodation, difficulties in power
      calculation, unavailability of appropriate lenses and thick lens optics. These
      difficulties and possible solutions are addressed referring to cases of IOL
      powers between 46 and 53 dptr.

PMID- 9009372
TI  - Posterior chamber lens implantation in children and infants.
AB  - Today the implantation of posterior chamber lenses in children and infants is
      still controversial. We report on the results of posterior chamber lens (PCL)
      implantation in a series of children with unilateral cataract, aged between 6
      months and 14 years.

PMID- 9009373
TI  - The fear of being left half-cured.
AB  - The complaint, "You are leaving me half-cured" is often heard from borderline
      patients in mid-recovery. They fear they are losing more than they could possibly
      gain; losing both the familiar sense of self given by their illness and the
      therapist, who will lose interest and abandon them far short of their fantasized
      ideal. Although cast in terms of an uncertain future, the phenomenon is to be
      understood in relation to change that has already occurred and requires working
      through its implications both for the patient's external adjustment and in
      relation to the patient's inner world.

PMID- 9009374
TI  - Why traumatized borderline patients relapse.
AB  - To be freed of longstanding painful symptoms or to become capable of functioning
      effectively has unconscious and sometimes conscious negative connotations for
      patients severely traumatized by childhood sexual abuse. These include rising
      expectations felt as coming both from within and without; disappointment that
      life can never make up for what has happened; loss of a justification for
      receiving care; fear that getting well invalidates the original trauma. Giving up
      illness may mean renouncing revenge and denying the seriousness of the childhood
      misery. To the extent that the torment of flashbacks and nightmares represents a
      continuation of the only family relationships the patient has known, losing these
      symptoms can feel as if being left entirely alone. The destructive impact of
      embittered and paranoid reactions unleashed by the experience of change for the
      better can be mitigated by the therapist's recognition of, and the focus upon,
      the negative meanings of progress toward health.

PMID- 9009375
TI  - Psychiatry behind the walls: mental health services in jails and prisons.
AB  - Throughout his professional career, Karl Menninger emphasized the importance of
      understanding criminal behavior and societal responses to such behavior. He
      focused on the need for more humane approaches within the criminal justice
      system. This article focuses on the current needs and anticipated directions for
      psychiatric services in prisons and jails, including comprehensive systems
      approaches that can facilitate better treatment and decrease repeat offenses.
      With the growing number of individuals being incarcerated in jails and prisons,
      and with higher percentages needing mental health services, it is important that
      effective mental health services be designed and implemented. Services should
      provide quality interventions and treatments for the inmates, must take into
      account and be respectful of the security needs of the facility, and must deal
      sensitively and thoughtfully with the stresses and factors that contribute to
      burnout among the professional staff and security officials. In this way, we can
      achieve part of Karl Menninger's dictum to provide better care for those who are
      unfortunate enough to have their behavior result in their being incarcerated in
      jails and prisons.

PMID- 9009376
TI  - The quiet revolution: consciousness raising and psychoanalytic practice.
AB  - The author recalls her early years of training in Topeka and links the radical
      changes in psychiatry that the Menningers were bringing about with her awareness
      of prejudice and with fomenting her revolutionary practices. She pinpoints some
      of the crucial experiences she had in her training and with her teachers that
      enabled her to exercise her social activism within her clinical practice. She
      details some of the ways in which psychoanalysis and feminism can interact
      fruitfully.

PMID- 9009377
TI  - Political bias, moral values, and spirituality in the training of
      psychotherapists.
AB  - Today psychotherapists face a challenge quite different from Karl Menninger's
      early efforts to foster an understanding between the new science of psychiatry
      and traditional religion. Today the mental health sciences are struggling with
      the contradictions and conflicts about society's values and spirituality that are
      currently vexing us all. The challenge today for psychotherapists is how to
      address values and spirituality professionally, ethically, and usefully in our
      work. This article looks at the scope of the task of training psychotherapists to
      work with values and spirituality in today's climate of amorphous values and
      culture wars.

PMID- 9009378
TI  - Nurturing scientific minds: Menninger at mid-20th century.
AB  - The beginnings of the Menninger School in 1946 witnessed a felicitous combination
      of inspiring and brilliant faculty, eager and intelligent students, a nurturing
      reciprocity between clinical excellence and research commitment, an open
      acceptance of incisive questioning of dogma and received knowledge, and an
      implicit tenure system, which made it possible to develop behavioral scientists
      who learned to pursue research activities and to administer clinical care. At
      that time, the relative absence of barriers between disciplines taught students
      how to forge multidisciplinary collaborations that strengthened their scientific
      efforts. The author ponders whether such training of clinical researchers can be
      re-created.

PMID- 9009379
TI  - The identity of psychoanalysis: the question of lay analysis.
AB  - This article, besides being a general historical account of the nature and
      meaning of the almost century-long controversy over "the question of lay
      analysis," also had a specific context and purpose. The author was invited to
      give the plenary keynote address to the winter meeting of the American Academy of
      Psychoanalysis in Santa Barbara, California, on December 9, 1994. After the
      passage of the Gaskill Committee proposals by the American Psychoanalytic
      Association in 1986, the alteration of the Regional Association agreement between
      the American and the International Psychoanalytical Association in 1987, and the
      settlement of the class-action lawsuit by clinical psychologists against the
      American and the International in 1988, this controversy over lay analysis had
      finally been resolved within the International and all its component
      organizations, including the American. The American Academy of Psychoanalysis,
      however, is one organization (with some overlap of membership with the American
      Psychoanalytic Association) that continues to maintain a bar against any members
      except medically qualified psychoanalysts. The author agreed to give the plenary
      address with the stipulation, which was accepted, that he could use the occasion
      to review this long history of the struggle over lay analysis, and to ask the
      Academy to reconsider its long-standing policies that now make it a lonely
      holdout against the evolution and resolution that has taken place in the
      overwhelming balance of organized institutional psychoanalysis worldwide.

PMID- 9009381
TI  - Transactions of the Topeka Psychoanalytic Society.

PMID- 9009380
TI  - Epilogue: graduate: educate thyself.

PMID- 9009382
TI  - Evidence for TB clustering in Vancouver: results from pilot study using RFLP
      fingerprinting.

PMID- 9009383
TI  - National Surveillance of Occupational Exposure to the Human Immunodeficiency
      Virus.

PMID- 9009384
TI  - Protocols help protect against getting HIV--but you have to use them.

PMID- 9009385
TI  - Emerging infectious disease: repeat of an old challenge.

PMID- 9009386
TI  - Control of imported communicable diseases: preparation and response.
AB  - Control of imported communicable diseases hitherto has been based on a paradigm
      of exclusion, isolationism and quarantine. Yet such policy is inconsistent with
      globalization of communication, commerce and travel, thus ignoring the potential
      for rapid dissemination of infectious disease worldwide. Prevention and
      containment strategies founded on such a premise ultimately cannot be effective.
      Instead, the perspective in control of communicable diseases must become
      international with monitoring and study of disease emergence, vector and
      reservoir patterns, and factors which facilitate and impede pathogen traffic. Our
      public health system must be reorganized with an international focus to ensure
      adequacy of surveillance mechanisms, related applied research, prevention and
      control strategies (including vaccination and information dissemination and
      education), and maintenance of optimal infrastructure--nationally, locally and
      internationally. Clear national and provincial contingency plans must be
      developed, ideally with international cooperation, for dealing with emerging
      infectious disease threats.

PMID- 9009387
TI  - Resilience in families: challenges for health promotion.

PMID- 9009388
TI  - Rickets prevention.

PMID- 9009389
TI  - Rickets prevention.

PMID- 9009390
TI  - Similar publications: need for referencing.

PMID- 9009391
TI  - Increasing evidence-based decisions about public health interventions.

PMID- 9009392
TI  - Suicides associated with the Jacques Cartier Bridge, Montreal, Quebec 1988-1993:
      descriptive analysis and intervention proposal.
AB  - Falls from heights represent an uncommon means of suicide. Regional variations
      are attributable to the presence of particular sites which attract suicidal
      individuals. The Jacques Cartier Bridge in Montreal is one such site, though less
      well known than North American sites such as the Golden Gate Bridge or Niagara
      Falls. According to Coroner's records, 54 suicides were associated with the
      bridge for the period 1988 to 1993. All but one of the suicides were the result
      of jumps from the bridge. The median age of victims was 30 years, and 46 of the
      victims were male. Bridge-specific verbalization of suicidal intent and prior
      history of medically diagnosed psychiatric disorders are frequently noted. Based
      on a review of the effectiveness of preventive measures, we propose limiting
      access to jumping by means of a fence along the bridge railing.

PMID- 9009393
TI  - Correlates of facial protection use by adult recreational ice hockey players.

PMID- 9009394
TI  - A community-based study of parents' knowledge, attitudes and beliefs related to
      childhood injuries.
AB  - This study assessed parents' knowledge of injury risks for children, attitudes
      within children's injury-risk behaviours, and beliefs related to a number of
      aspects of childhood injuries. Parents completed questionnaires and participated
      in discussions using scenarios depicting child-injury situations that involved a
      parent and child. Results indicated that parents view injuries largely as a
      natural consequence of childhood and they believe children learn about risk
      avoidance from injury experiences. Parents' responses did not indicate a strong
      belief that injuries to children are preventable or that they should assume
      primary responsibility for preventing injuries to children. Parents readily
      identified potential injury consequences and alternative behaviours but provided
      a number of rationales for making choices that place their child at injury risk:
      explanations related to convenience, minimizing stress, placing their own goals
      as a priority, and believing they can keep the child safe in a hazardous
      situation. Injury prevention programming that targets parents needs to focus on
      increasing awareness of the scope of the problem and altering attitudes and
      beliefs related to prevention.

PMID- 9009395
TI  - Variations in breast conservation surgery for women with axillary lymph node
      negative breast cancer in British Columbia.
AB  - A population-based study was conducted including all women diagnosed in British
      Columbia in 1991 with invasive node negative breast cancer (n = 942) in order to
      identify factors associated with variation in use of breast conserving surgery
      (BCS) and to determine if provincial practice guidelines were followed. Patient,
      disease, treatment and physician-specific information was abstracted from medical
      records and original source documents. 413 (44%) patients received BCS (51% and
      23% in surgical candidates and non-candidates, respectively). Significant
      independent factors associated with BCS included patients' age, residence, family
      income, tumour size, tumour location, and extent of ductal carcinoma in-situ. Age
      and income had a significant interaction with stronger income effects in older
      women. A strong surgeon effect was observed which was not explained by measured
      surgeon attributes. Expansion of radiation treatment facilities may help address
      access issues. Further examination of the patient-physician relationship and of
      ways to assist patients in decision making is needed.

PMID- 9009396
TI  - Tuberculosis in Nunavik, 1980-1994.

PMID- 9009397
TI  - Asthma and limitation of activities in Fort Saskatchewan, Alberta.
AB  - A study was undertaken to determine the prevalence and impact of asthma in
      elementary school children in Fort Saskatchewan, Alberta. Questionnaires were
      distributed at all seven elementary schools and were completed by the parents. Of
      the 1,457 eligible students in grades one to six, questionnaires were returned
      for 1,083 (74%). A history of physician-diagnosed asthma was reported for 12.9%
      of the children: 16.0% of boys and 9.7% of girls. Currently, 9.9% of children had
      asthma: 11.6% of boys and 8.2% of girls. Compared to children without, those with
      asthma were more than 10 times as likely to have to limit their activities for a
      health reason (70.5% versus 6.6%), missed school more often for health reasons
      (32.7% versus 14.8% missed two or more days in the previous month), reported more
      "colds" in the previous year and were three times as likely to have had
      pneumonia. The prevalence of asthma is approximately twice as high as that found
      in children across Canada and underscores the need to determine risk factors for
      asthma in this population. The finding that 1 in 10 children had asthma
      emphasized the need for programs aimed at children with asthma.

PMID- 9009398
TI  - Evidence for occupational asthma among compensation claimants at a polyurethane
      utilizing facility.

PMID- 9009399
TI  - Missed opportunities for measles immunization: Waterloo region, Ontario, 1990
      1991.

PMID- 9009400
TI  - Immunity against measles in school-aged children: implications for measles
      revaccination strategies.
AB  - Measles serum antibody levels were determined by plaque reduction neutralization
      (PRN) test in 1,075 children in the age bracket of 5 to 17 years who received a
      single dose of measles-mumps-rubella (MMR II) vaccine at one year of age. Of
      these, 297 children (28%) had measles PRN titres < 120 which may not be
      protective against measles infection. The proportion of susceptible children by
      age ranged from 14 to 35%; however, there was no consistent age-dependent trend
      in susceptibility rates. The study data indicate the decline in protective
      immunity occurs before five years of age, and the proportion susceptible
      increases only slightly thereafter. This supports the current move towards a two
      dose immunization strategy in the control and elimination of measles, with the
      second dose being given before school entry. The present data also underscore the
      need to consider a mass catch-up immunization program in the interim to prevent
      potential outbreaks of measles in school settings. The combination of the above
      approaches, if implemented as soon as possible, can potentially eliminate
      indigenous measles in Canada by the year 2000, the target date set by the Pan
      American Health Organization.

PMID- 9009401
TI  - Randomized trials of public health interventions reported in the Canadian Journal
      of Public Health: 1966 to 1996.

PMID- 9009402
TI  - Evaluation research in public health: barriers to the production and
      dissemination of outcomes data.
AB  - Health outcomes are becoming the currency of health care exchange, and a call for
      evidence dominates decision making at all levels. This discussion paper reviews
      methodological and sociopolitical barriers that impede the production and
      dissemination of outcome research in public health, with particular reference to
      nursing. Barriers to the production of high-quality research evidence include
      inaccessible graduate education and inadequate research funding. Also, randomized
      controlled trials (the ideal design for interventions studies) are uniquely
      difficult to implement for public health services. Practical and ethical
      difficulties arise in defining the intervention, implementing random allocation
      methods, selecting and measuring outcomes, and articulating adequate theoretical
      frameworks. When health care activity is defined as output, there is a tendency
      to exclude the ethical standing of preventive, supportive and communitarian
      functions. The production and interpretation of research results must remain part
      of a social, political and ethical debate, not a purely scientific one.

PMID- 9009403
TI  - Predicting future long-term-care needs in a community.
AB  - Under current financial restraints, planning for the future long-term-care needs
      of older Canadians is coming under increasing scrutiny. Even though health care
      is moving to a community-based system (i.e., deinstitutionalization), this is not
      necessarily the most cost-effective strategy for severely disabled older adults.
      Three models are used in the present paper to estimate the number of severely
      disabled (two or more ADL disabilities abilities) older adults expected in the
      next 5 to 10 years in a small community in Northern Ontario. While mortality and
      disability rates are the main predictors, it was also necessary to consider
      additional factors particular to the community in question. It is suggested that
      for long-term-care planning to be effective and economically sound, similar
      strategies will be needed throughout Canada.

PMID- 9009404
TI  - The work of visiting homemakers in the context of cost cutting in long-term care.
AB  - Policy making and service organization in long term care for frail elderly people
      are dominated by concern with reducing institutional costs and increasing the use
      of relatively inexpensive home care services. Little attention has been focussed
      on the implications of cost cutting for those at the point of home care service
      delivery. A qualitative study of visiting homemakers sought to explore these
      implications. A sample of visiting homemakers working in southern Ontario took
      part in semi-structured interviews about their work experiences. Analysis of
      interview transcripts revealed the exploitative potential and tensions introduced
      by funding restraint, and suggested that home care workers' ability to deliver
      high quality, personalized care is compromised by organizational practices that
      speed up and intensify their work. Further research on home care providers and
      their elderly clients is needed to document the outcomes of economically driven
      public policies for those who deliver and receive them.

PMID- 9009405
TI  - The scientific and technological milestones of orthopaedics and traumatology.

PMID- 9009406
TI  - Giant cell tumor of the vertebral column.
AB  - The authors report 23 cases of giant cell tumor (GCT) of the mobile spine,
      treated between 1975 and 1993, with mean follow-up of 9 years. The series was
      homogeneous in terms of diagnosis, staging, and treatment, carried out at the
      Rizzoli Orthopaedic Institute, and isolated from a series of 28 cases recorded at
      the Tumor Center of the Rizzoli Institute. Five of the cases were excluded either
      because of insufficient documentation (4), or because the tumor had occurred on
      Paget's disease (1). GCT of the spine is a rare disease, and has a favorable
      diagnosis if treatment is correct, consisting in intralesional curettage of
      "active" forms and extracapsular curettage associated with adjuvant radiotherapy
      (or en bloc resection) in "aggressive" forms.

PMID- 9009407
TI  - X-ray evaluation of interferential femoral screw positioning in ACL
      reconstruction.
AB  - In a total of 27 patients the authors performed reconstruction of the anterior
      cruciate ligament using the mid third of the free patellar tendon (bone-tendon
      bone), stabilized with two interferential wires, using a mini-arthrotomic half
      tunnel in-out method. X-ray examination in two orthogonal views allows for an
      evaluation of the orientation of the femoral screw in relation to the joint plane
      and the diaphyseal axis, and its relationship with the bone graft, thus obtaining
      useful information on its anchoring. The method used is that reported by Lemos et
      al. (1993). The results obtained agree with those reported by the American author
      and substantiate the reliability of the method.

PMID- 9009408
TI  - Wear in carbon fiber-reinforced polyethylene (poly-two) knee prostheses.
AB  - The authors report a case of massive wear of carbon fiber-reinforced polyethylene
      used as an insert in a knee prosthesis. The finding, which was studied under a
      scanning electron microscope, in agreement with mechanical resistance and
      laboratory testing reported in the literature, confirms that this composite
      material (poly-two) is not more advantageous to use that ultra-high molecular
      weight polyethylene in terms of wear, despite favorable experimental premises.

PMID- 9009409
TI  - Static assembly of the CEB system in per-subtrochanteric fractures.
AB  - The CEB surgical system constitutes a new means of intramedullary dynamic
      osteosynthesis for the surgical treatment of pertrochanteric fractures. The
      effectiveness of results obtained in more than 250 cases has encouraged use of
      the method for the treatment of fractures in the femoral subtrochanteric region,
      too, with a static assembly that involves a supplementary oblique distal screw.
      The distal screwing phase proved to be very easy; the authors recommend its use
      in all of cases of strongly unstable lateral fractures.

PMID- 9009410
TI  - Aseptic nonunion of the tibia treated by intramedullary osteosynthesis.
AB  - The authors report 52 cases of aseptic nonunion of the tibia treated by
      intramedullary osteosynthesis. The means of synthesis used were the Kuntscher
      nail, the Eiffel Tower Rush nail, and the Grosse-Kempf nail. Which means of
      synthesis was used depended on the site and the features of the nonunion. Healing
      occurred in all of the cases after an average of 5 months. Mean follow-up was 4.5
      years.

PMID- 9009411
TI  - Lengthening of the lower limbs in Ollier's disease: problems related to surgery.
AB  - Ollier's disease is a chondromatosis of the long bones that occurs rarely but
      that is highly disabling because it causes severe dysmetria and deformity of the
      lower limbs. Surgical correction of these skeletal changes is obstructed by poor
      mechanical resistance of the bone tissue affected and by the amount of
      lengthening required to even the lower limbs. It is the purpose of this study to
      indicate the surgery of choice for the treatment of this disease, comparing the
      two most recent methods used: Wagner's technique and the Ilizarov method. The
      latter is more reliable in terms of mechanical hold and the possibility of
      correcting severe deformities, producing bone regenerate of excellent quality
      even in major lengthening procedures. These results were obtained by adapting the
      Ilizarov method to the features of the chondromatous bone, thanks to the extreme
      malleability of the circular external fixator.

PMID- 9009412
TI  - Reinnervated free gracilis muscle transplantation in the treatment of Volkmann's
      syndrome of the forearm.
AB  - Between 1989 and 1994 free gracilis muscle reinnervation was used to treat three
      patients severely affected with Volkmann's syndrome of the forearm. All three
      patients were males and they had supracondyloid fracture of the humerus, treated
      nonsurgically an average of 7.6 years previously. Mean age at the time of surgery
      was 19.3 years. The flap was transplanted in flexor function of the fingers in
      two of the patients, in extensor function of the wrist in one. Electromyography
      and successive clinical monitoring revealed an increase in contractile strength
      up to one year after surgery. In the first two cases final hold strength exceeded
      by more than 50% that of the contralateral limb, in the third case excursion of
      the wrist which could not be quantified, but which was useful for elementary
      activities was recovered. When myotendinous units for transplantation are not
      available, free gracilis muscle reinnervation constitutes a valid surgical
      solution in cases of severe Volkmann's syndrome of the forearm.

PMID- 9009413
TI  - Isokinetic testing to evaluate patients submitted to surgery for the treatment of
      surgical lesion of the rotator cuff.
AB  - A total of 100 cases surgically treated for rupture of the extra-rotator cuff
      were evaluated by isokinetic testing. Results were evaluated after a period of
      time ranging from 1 to 4 years, based on the Constant system, defining the type
      of lesion of the cuff based on the Snyder classification system, and measuring
      strength postsurgery using isokinetic testing after 3 and 6 months, and 1 year.
      Isokinetic testing made it possible to accurately evaluate which patients are
      capable of obtaining better recovery, and how much time is required for
      physiotherapy for postoperative rehabilitation, also allowing for correction on
      an individual basis of any muscular imbalance.

PMID- 9009414
TI  - The conservative treatment of xanthoma of the Achilles tendon in patients
      affected with type IIA hypercholesterolemia.
AB  - Treatment of xanthoma of the Achilles tendon has up until the present been based
      on partial or total surgical resection of the affected tendon. Because of the
      different results of surgical treatment our study was aimed at using clinical and
      ultrasound data to reveal the effectiveness of hypocholesteremic medical therapy
      in 39 cases of tendinous xanthoma.

PMID- 9009415
TI  - Specific antibiotic therapy by needle-aspiration for the treatment of
      osteomyelitis of the pubis. A description of two clinical cases.
AB  - The authors describe two cases of osteomyelitis of the pubis, that exemplify the
      difficulty of differential diagnosis, as symptoms at the onset are "masked" by
      previous urologic pathologies (aspecific acute epididymitis and, respectively,
      urethritis cystica in the sequelae of radical prostatectomy). The x-ray findings
      for osteolysis make a local biopsy necessary; the lesion may in fact, be mistaken
      for a neoplasm, particularly in patients who have previously been submitted to
      pelvic visceral surgery for the treatment of tumor. The needle-aspiration
      procedure and the execution of a cultural examination, in addition to a
      cytological one, provide unmistakeable data for diagnosis and treatment.

PMID- 9009416
TI  - Scoliosis in Escobar syndrome (multiple pterygium syndrome). Description of two
      cases.
AB  - The authors report two cases of scoliosis in Escobar syndrome. Both of the
      patients were submitted to surgical treatment. A fair amount of correction was
      obtained in the first case, simple stabilization of the deformity was obtained in
      the second. Our experience confirms the fact that scoliosis may progress
      considerably in Escobar syndrome, requiring early surgical treatment.

PMID- 9009417
TI  - Tuberculosis of the lower cervical spine: a description of two cases.
AB  - Tubercular infection is a rare occurrence in the lower cervical spine. The
      isolated involvement of the posterior arch is particularly rare, and the very few
      cases in which it is reported at the thoracic or lumbar levels were principally
      observed in immunodepressive patients. It is the purpose of this study to
      describe two cases of tuberculosis of the lower cervical spine with neurological
      deficit: one expansive neoformation at the level of the arch of C7, with saving
      of the vertebral body and the discs, and a spondylodiscitis at C4-C5, treated
      conservatively, the healing process of which was followed by MRI.

PMID- 9009418
TI  - Epidural angioma: description of one case.

PMID- 9009419
TI  - Vertical facial growth and statural growth in girls: a longitudinal comparison.
AB  - Individual and average growth patterns of the facial dimensions Nasion-Gnathion
      and Sella-Gonion, as related to statural growth were studied. The sample
      consisted of 134 girls aged 7-14 years. Data were analysed using a multivariate
      extension of the multilevel model for longitudinal data. The results confirmed
      that the mean growth curves of Nasion-Gnathion, Sella-Gonion and body height
      parallel each other to a large extent. At an individual level it appeared that
      the pubertal growth spurt of body height and the growth spurts of both facial
      dimensions are coincident. The major results of the present study pertain to the
      dynamic (age-dependent) relationship between statural growth and the growth of
      the face. It appears that there exists a stronger relationship between the growth
      velocities of standing height, Sella-Gonion and Nasion-Gnathion than between the
      actual lengths of the three variables themselves. The strongest relation was
      found between the growth velocity of body height and that of Sella-Gonion. These
      findings may be a contribution for diagnosis and treatment planning of individual
      cases.

PMID- 9009420
TI  - The cephalometric morphology of patients with obstructive sleep apnoea (OSA).
AB  - This prospective study analysed the lateral cephalometric radiographs of 59
      dentate, white, Caucasian males. Thirty-five patients with proven obstructive
      sleep apnoea (OSA) formed the experimental group, while 24 subjects with no
      history of respiratory disease acted as controls. Radiographs were traced and
      digitized, and both hard and soft tissue features were compared between the
      groups. The pooled data were then subjected to discriminate analysis. Although
      conventional cephalometric measurements did not differ between the two groups,
      significant reductions were found in the lengths of the mandibular body and
      cranial base and in cranial base angulation in OSA subjects. The width of the
      oropharynx was significantly narrower in this group, particularly in the post
      palatal region. The area of the soft palate was increased although that of the
      tongue was not. Intermaxillary space length (the distance between the posterior
      pharyngeal wall and the tip of the lower incisor) was decreased, and thus the
      area in which the tongue had to function was smaller in OSA subjects. From the
      discriminant analysis, two four-variable models were derived, both of which
      provided 100 per cent discrimination between the OSA and normal subjects. For the
      first model the entire OSA group was used: for the second, only obese OSA
      subjects (those a body mass index > 25) were chosen. The combination off a short
      mandible and intermaxillary space, with an enlarged soft palate but decreased
      pharyngeal airway has relevance to the effective management of OSA. In selected
      patients, advancement of the lower jaw by a nocturnal mandibular repositioning
      splint may be indicated. The orthodontist would seem to be in a unique position
      to assist in both the identification and treatment of these subjects.

PMID- 9009421
TI  - Airway dimensions and head posture in obstructive sleep apnoea.
AB  - The present cephalometric study aimed to describe the antero-posterior diameters
      of the pharyngeal airway in a sample of 50 male obstructive sleep apnoea (OSA)
      patients and a reference sample of 103 male students, and to examine the
      relationship between these diameters and the posture of the head and the cervical
      column. Subjects were recorded in the cephalometer standing with the head in its
      natural position (mirror position). Pharyngeal airway diameters were measured at
      seven levels ranging from the maxillary tuberosity to the vallecula of the
      epiglottis. The largest difference was observed at the level behind the soft
      palate where the diameter was 50 per cent narrower in the OSA sample than in the
      reference sample. Extension of the cranio-cervical angle and forward inclination
      of the cervical column were correlated with an increase in the three most caudal
      airway diameters in the OSA sample: at the uvula, the root of the tongue, and the
      epiglottis, but only to increase in the lowest diameter in the reference sample.
      The findings were considered to reflect a compensatory physiological postural
      mechanism that serves to maintain airway adequacy in OSA patients in the awake
      erect posture, most efficiently so at the lowest levels of the oropharyngeal
      airway.

PMID- 9009422
TI  - Tissue response to space closure in monkeys: a comparison of orthodontic magnets
      and superelastic coil springs.
AB  - Interest in using magnets for generating orthodontic forces started with the
      widespread availability of rare earth magnetic alloys. In vivo studies have
      indicated that a static magnetic field and/or corrosion products from the
      magnetic materials may induce biological effects when in close contact with cells
      or tissues. In the clinical situation, orthodontic magnets are often situated
      some distance away from the gingiva and bone. Consequently, the previously
      observed biological effects may not be found in an experimental situation
      mimicking the clinical setting. Thus, the present experimental study was
      undertaken to test this hypothesis using commercially available cobalt-samarium
      magnets for orthodontic treatment in comparison to treatment with Sentalloy
      closed coil springs with respect to possible side effects on alveolar bone
      growth, gingival epithelial thickness as well as rate of space closure. Corrosion
      of the uncovered areas of the magnets was already evident after 6 weeks. No
      statistical differences were found between the magnet and coil spring specimens
      with respect to rate of space closure, bone formation or epithelial thickness.
      The only two variables that differed significantly between magnet and coil spring
      specimens was that there were more resorption and more tetracycline labelled
      osteocyte lacunae under the magnets. In conclusion, although some marginal
      statistical differences were found between the magnet and coil spring specimens
      with respect to cell and tissue reactions, the near lack of cell and tissue
      effects of the magnets in the present clinical experimental situation compared to
      previous studies in which the magnets were positioned in close contact with the
      tissue under study, indicate limited adverse clinical effects.

PMID- 9009423
TI  - Agenesis of mandibular second premolars. Spontaneous space closure after
      extraction therapy: a 4-year follow-up.
AB  - The aim of this study was to investigate the space closure and occlusal changes
      in 11 subjects (mean age 11.8 years) with normal occlusion and agenesis of the
      mandibular second premolar, after extraction of the mandibular secondary primary
      molar and the maxillary second premolar on the side of the agenesis. The
      treatment started when the first premolars came into occlusion and the subjects
      were followed for 4 years. Dental casts were taken at the start of treatment and
      after 1, 2 and 4 years, and lateral cephalograms were taken at the start of
      treatment and after 2 and 4 years. Space closure, sagittal movements, rotational
      movements, and tipping of the first molars and first premolars and dental midline
      shift were measured on photographs of dental casts. Sagittal movement of the
      incisors was measured on lateral cephalograms. The results showed that most of
      the extraction space closed during the first year (55 per cent in the maxilla, 46
      per cent in the mandible) and at the end of the follow-up period 89 per cent of
      the extraction space closed in the maxilla and 80 per cent in the mandible,
      leaving a mean residual extraction space of 0.9 and 2 mm respectively. In the
      maxilla, 70 per cent of the extraction space closed by mesial and rotational
      movements of the first molars. Maxillary premolars moved distally, rotated and
      tipped only during the first year of observation. In the mandible, the space
      closure occurred by mesial/rotational movements and tipping of first molars and
      distal movement and tipping of the first premolars. Unilateral extraction had no
      influence on the maxillary midline while it caused a statistically significant
      mandibular dental shift to the extraction side. Extraction therapy had no impact
      on the overjet, overbite or incisor inclination.

PMID- 9009424
TI  - The effects of food consistency on maxillary growth in rats.
AB  - The effect of food consistency on the bone appositional pattern at the growth
      site in the palatal region of the maxillary complex in growing rats was examined
      by quantitative analysis employing bone histomorphometry. Sixty inbred male rats
      aged 14 days in the weaning period were divided into two groups. One group was
      fed a conventional solid diet in addition to milk, while the other received the
      same diet but in liquid form in addition to milk, They were weaned at 21 days of
      age. Vital staining was employed to enable a longitudinal recording of bone
      apposition. In rats fed a liquid diet, the amount of bone apposition on the
      occlusal surface of the palate was reduced in the region between between the
      first molars, but was increased in the region between the third molars,
      indicating a more anteriorly directed growth rotation of the palate. The width
      and ossification rate of the synchondrosis of the midpalatal suture was smaller.
      Furthermore, lateral growth of the maxilla was inhibited considerably in the
      distal area. In conclusion, this study shows that food consistency affects the
      bone appositional pattern at the growth site in the palatal region of the
      maxillary complex. The results also suggest that the difference in the growth
      pattern in the upper viscerocranium induced by different food consistencies is
      caused not only by a difference in mechanical force of the masticatory muscles
      acting on the muscle insertion areas but also by a difference in the growth
      pattern in the region which receives occlusal loading.

PMID- 9009425
TI  - An investigation of tooth size in Northern Irish people with bimaxillary dental
      protrusion.
AB  - This study examined tooth size in a sample of thirty Northern Irish people with
      bimaxillary dental protrusion. The mesiodistal diameters of all permanent teeth
      (excluding second and third molars) were measured. The tooth sizes were compared
      with a control group who did not have bimaxillary dental protrusion. The results
      revealed that, on average, tooth size for the overall maxillary and mandibular
      dentition was 5.7 per cent larger in the bimaxillary sample than in the control
      sample.

PMID- 9009426
TI  - A comparison of crown size dimensions of the permanent teeth in a Nigerian and a
      British population.
AB  - This investigation was undertaken to compare the mesio-distal and bucco-lingual
      crown dimensions of the permanent teeth in Nigerian and British populations. The
      study sample consisted of 30 pairs of study models of children from each of the
      two populations. The children were matched for sex. The mean age for the Nigerian
      and British samples was 12.5 +/- 1.4 years and 12.9 +/- 1.2 years respectively.
      No left-right side differences were observed (P > 0.05). The results indicate
      that the mesio-distal crown diameters were consistently larger in the Nigerian
      sample. With the exception of mandibular central incisors and maxillary canines
      there were no statistically significant differences in bucco-lingual crown
      diameters in the two populations.

PMID- 9009427
TI  - Combined effects of errors in frontal-view asymmetry diagnosis.
AB  - The aim of the present investigation was to determine the relative extent of
      geometric error and errors in point identification in postero-anterior
      roentgenography. In one series of tests a group of dry human skulls was used, and
      the same cephalometric landmarks were identified twice by two orthodontists,
      using postero-anterior roentgenographs, first using the dry skulls as such, and
      then the same skulls with metal markers inserted to show the exact locations of
      the cephalometric points. Consistency and normal variation in the reproducibility
      of head position in the cephalostat between repeated roentgenographs were studied
      by a photographic technique in a group of young healthy adults, measuring the
      extent of minor head movements. Geometric error was calculated using a computer
      aided design program (CAD) by rotating the three-dimensional co-ordinates of the
      cephalometric landmarks and thus obtaining projection error in the frontal view.
      Accuracy in cephalometric point identification was best in dental landmarks and
      vertical orientation of superior orbital margins. Geometric error was least when
      landmarks near the anterior midsagittal plane, such as upper and lower dental
      midlines or point gonion were compared with each other. Width measurements from
      frontal-view cephalograms are most sensitive to minor movements in head posture.
      Due to combined errors, the use of width measurements in facial asymmetry
      diagnosis should not be used since variance in errors in landmark identification
      can be larger than that in actual landmark location.

PMID- 9009428
TI  - The prevalence of malocclusion in children with cerebral palsy.
AB  - The prevalence of malocclusion in children with cerebral palsy was studied by
      comparison with a normal control group. The prevalence of drooling and
      prematurity was also assessed as well as the degree of mental handicap. Results
      showed an increased prevalence of malocclusion in children with cerebral palsy.
      Cerebral palsied children are likely to have a significantly increased overjet (P
      < 0.001) when compared with normal children. The comparatively small sample sizes
      precluded firm conclusions being drawn regarding other group comparisons (such as
      comparing children with cerebral palsy with and without a mental handicap) but
      there may be a tendency towards the more handicapped group having a Class II
      malocclusion.

PMID- 9009429
TI  - Patterns and prediction of orthodontic treatment course.
AB  - Most attempts at the identification and prediction of treatment-related changes
      and outcome in orthodontics thus far have relied upon single biometric parameters
      instead of employing a systemic and ecological approach. The concept of facial
      harmony and the availability of sophisticated multivariate statistics offer new
      chances for a deeper understanding of the mechanisms of change. A longitudinal
      study has been conducted on approximately 500 youths aged 9-11 years, on average.
      Numerous parameters of cephalometric analysis, study casts, growth, treatment
      regimen and patient co-operation were assessed at the onset of treatment (T0) and
      after 1 year (T1) to determine treatment-related changes under therapy with
      removable appliances. Exploratory cluster analyses were based on five fundamental
      cephalometric parameters (SNA, SNB, ML-NSL, NL-NSL, NS-Ba) that establish an
      operational approach to harmonious facial relations (Segner and Hasund, 1991). As
      a first step, analyses were restricted to 281 Class II division 1 patients
      selected for good co-operation by an expert rating by the first author on a three
      point rating scale. They all were treated with bionators either with anterior or
      posterior traction. Both subgroups were studied separately. Based on cluster
      analytic procedures, different patterns of change were identified for both types
      of appliance. A slight tendency toward harmonization of the initial skeletal
      relations was observed throughout all subgroups, with reactions being most
      obvious in the maxilla. The clusters produced for either appliance group were
      then screened for additional predictors of group membership by means of
      discriminant analysis. The findings are discussed in terms of the suitability of
      the methodological approach chosen.

PMID- 9009430
TI  - The extent of enamel surface fractures. A quantitative comparison of thermally
      debonded ceramic and mechanically debonded metal brackets by energy dispersive
      micro- and image-analysis.
AB  - This clinical study investigated the practical value of two methods for debonding
      brackets attached by the adhesive Concise to acid-etched enamel surfaces. Forty
      two Ultratrimm Standard metal brackets and 42 Fascination ceramic brackets were
      collected from juvenile patients undergoing orthodontic treatment. All metal
      brackets were mechanically debonded by a conventional bracket removal plier,
      whereas the ceramic brackets were thermally debonded by a commercial Dentaurum
      ceramic debonding unit. All brackets were evaluated by scanning electron
      microscopy for the morphology of their adhesive fracture surfaces and for the
      occurrence of mineral-like particles attached to the adhesive fracture surfaces.
      These particles were analysed by an energy dispersive X-ray microprobe for their
      Ca/P ratios and by image analysis of scanning electron micrographs for
      measurement of their areas. The scanning electron micrographs showed 4 types of
      debonding fractures. The most frequent fracture was type 1 (between adhesive and
      bracket base) and type 2 (between adhesive and enamel surface). In the group of
      mechanically debonded metal brackets type 1 (38 per cent) and type 2 (45 per
      cent) showed a similar frequency, whereas thermally debonded ceramic brackets
      predominantly showed fracture type 1 (79 per cent) and only a minor percentage of
      type 2 (11 per cent). A statistical evaluation was applied to estimate the range
      of reproducibility of fracture types with a 95 per cent confidence interval
      (level of significance alpha = 5 per cent). In both groups the microprobe
      analysis of fracture surfaces lying completely or partly between adhesive and
      enamel surface identified the mineral-like particles as enamel mineral. They
      occurred partly as single particles (range of thickness: 5-25 microns, mean area:
      3500 microns2) and partly as a coherent covering with a total area of 1.9-5.8
      mm2. It is concluded that the thermodebonding technique is superior to
      conventional mechanical debonding, because the frequent occurrence of fracture
      type 1 after thermodebonding affords a protection for the enamel surface, whereas
      mechanical debonding entails a comparatively high risk of enamel fractures.

PMID- 9009431
TI  - Nasal obstruction.

PMID- 9009433
TI  - Nasal obstruction.

PMID- 9009432
TI  - Nasal obstruction.

PMID- 9009434
TI  - Publish or perish: prospects for European Hematological Journals.

PMID- 9009435
TI  - ABO genotyping in Italian blood donors.
AB  - BACKGROUND: Traditional ABO blood group serology is based on the immunoreactivity
      of antisera with the carbohydrate A, B and H antigens. Progress in the molecular
      biology of the ABO system has recognized the molecular basis of the red cell
      (RBC) antigens and has provided a genetic model for ABO polymorphism at the
      molecular level. Recently, this genetic model was tested in a large number of
      individuals. MATERIALS AND METHODS: In this study we applied DNA analysis to
      determine the frequency of ABO genotypes in a group of blood donors for whom the
      ABO type was known. Two hundred and fifty healthy Italian blood donors were
      analyzed using polymerase chain reaction (PCR) to amplify two different regions
      of genomic DNA, each of which contained a different nucleotide polymorphism. The
      amplified product was digested with 4 restriction enzymes that revealed
      differences among A, B and O individuals. To analyze the genes at polymorphic
      sites 261 and 703 we used the restriction enzymes BstE II and Kpn I, and Hpa II
      and Alu I and compared the PCR determined genotypes to serologically determined
      phenotypes. RESULTS AND CONCLUSIONS: The results were consistent for all
      unrelated individuals; however, 2 of 100 individuals with the 0 phenotype carried
      one allele that differed from the proposed genetic model. This novel O allele,
      termed 0(2) by Yamamoto et al., was found in our series with a frequency of 1%.
      The blood group AB0 genotype of 250 healthy Italian blood donors was: 13
      AA/AO(2), 37 AO(1), 11 BB, 39 B0(1), 50 AB, 98 0(1)0(1) and 2 0(1)0(2). This
      method should be applicable not only in forensic medicine but also in
      immunohematology when serology fails.

PMID- 9009436
TI  - In vitro effect of reduced glutathione on platelet function.
AB  - BACKGROUND: Generation of reactive oxygen species has been suggested to represent
      an important regulatory mechanism of platelet reactivity in both physiological
      and pathological conditions, and free-radical scavengers may inhibit platelet
      activation. The purpose of the present study was to investigate the effect of
      reduced glutathione (GSH) on different platelet functions stimulated by ADP,
      collagen or PAF. METHODS: Platelet aggregation was investigated by Born's method.
      TxB2 and PDGF levels were measured by radioimmunoassay. RESULTS: GSH at the
      lowest dose (1 mM) did not significantly modify aggregation, TxB2 production or
      PDGF release induced by ADP or PAF, while at higher concentrations (3 mM or 10
      mM) it significantly inhibited all parameters. Collagen-induced platelet
      activation was remarkably less sensitive to GSH, since aggregation was not
      significantly reduced, while TxB2 production was reduced by GSH when employed at
      concentrations of 3 mM or 10 mM, and PDGF release was inhibited only by the
      highest dose (10 mM). IC50 for inhibition of platelet aggregation, TxB2
      production and PDGF release were between 1.43 and 2.36 mM when platelets were
      stimulated with ADP, between 2.23 and 8.90 mM when PAF was used and between 8.00
      and 16.30 mM when collagen was the agonist. CONCLUSIONS: Our data suggest that
      GSH may act as a physiological inhibitor of platelet activation and may therefore
      contribute to the regulation of platelet reactivity.

PMID- 9009437
TI  - CCNU, vinblastine, procarbazine and prednisone (CVPP) with extended-field
      radiotherapy in the treatment of early unfavorable Hodgkin's disease. A
      prospective study on behalf of the Gruppo Italiano per lo Studio dei Linfomi
      (GISL).
AB  - PURPOSE: To test the adequacy of the CVPP four-drug regimen as ancillary
      chemotherapy associated with extended-field radiotherapy in the treatment of
      early, unfavorable, clinically staged Hodgkin's disease. PATIENTS AND METHODS:
      The population of this prospective, multicenter study consisted of 49 patients
      with stage I-II disease, associated with bulky involvement or unfavorable
      histology (lymphocyte-depleted nodular sclerosis or lymphocyte depletion),
      systemic symptoms or extranodal involvement, or presenting with stage III A
      favorable-histology disease, with or without extranodal involvement. RESULTS:
      Complete remission was achieved in 39 patients, partial remission in 2, while 8
      patients did not respond. Four patients have relapsed so far (median follow-up:
      43 months), all of whom were subsequently rescued with different salvage
      treatments. Dose intensity (mean +/- SD: 0.83 +/- 0.12) and hematological
      toxicity (including 2 deaths from infection) were higher when RT followed CT than
      when it was interposed in the middle of the 6 cycles. No growth factors were
      used. Nonhematological toxicity was very low and fully tolerable. CONCLUSIONS:
      Results confirmed the mild neurological and gastroenteric side effects of CVPP
      that make it an interesting MOPP-variant regimen. This combination seems most
      indicated when a regimen devoid of cardiac and pulmonary toxicity is required for
      association with full-dosage mediastinal radiotherapy, as is often the case in
      early, unfavorable Hodgkin's disease. The optimal sequence consists of
      radiotherapy administered after completion of the chemotherapy program. The use
      of growth factors for correction (or prevention) of marked leukopenia seems
      appropriate.

PMID- 9009439
TI  - The F-MACHOP regimen in the treatment of aggressive non-Hodgkin's lymphomas: a
      single center experience in 72 patients.
AB  - BACKGROUND: Since July 1991 we have employed the F-MACHOP regimen for the
      treatment of aggressive non-Hodgkin's lymphomas (NHL). The aim of the present
      study was to evaluate the response rate and the toxicity of this chemotherapy
      program. PATIENTS AND METHODS: Seventy-two consecutive patients entered the study
      and were treated with the F-MACHOP regimen for 6 planned courses, given every 21
      days. G- or GM-CSF were administered whenever required. RESULTS: Sixty-six
      patients (92%) obtained a response: 38 (53%) a complete remission (CR) and 28
      (39%) a partial remission (PR); 4 (6%) proved to be resistant and 2 (3%) died of
      chemotherapy-related toxicity. Fifty-seven patients with a good performance
      status were subsequently selected to undergo autologous stem cell transplantation
      (ASCT). During chemotherapy, grade III-IV neutropenia was observed in 59% of the
      patients; a significant drop in hemoglobin levels was detected, with blood
      transfusions being required in 21% of the cases; platelet counts were unaffected.
      The main extrahematological toxic events were: alopecia (100% of the patients),
      osteoarthromyalgias (58%), grade I-II neuropathy (53%) and grade I-II hepatic
      toxicity (43%). CONCLUSIONS: Our study confirms the efficacy of the F-MACHOP
      regimen in obtaining a high rate of response (CR + PR) in most aggressive NHL
      cases, with an acceptable toxicity and a low rate of toxic deaths. This regimen
      enables the majority of patients to be selected for ASCT as consolidation therapy
      without significant toxicity.

PMID- 9009438
TI  - High efficacy of fludarabine-containing therapy (FLAG-FLANG) in poor risk acute
      myeloid leukemia.
AB  - BACKGROUND: Elderly patients with acute myeloid leukemia (AML) those refractory
      to induction chemotherapy and those with so-called secondary leukemia have
      unfavorable prognoses and require innovative therapeutic approaches. Fludarabine
      allows an increased accumulation of Ara-CTP in leukemic cells and inhibits DNA
      repair mechanisms; therefore its association with Ara-C and mitoxantrone results
      in a synergistic effect. MATERIALS AND METHODS: From May 1993 to February 1996,
      fludarabine-containing regimens (FLAG and FLANG) were employed as induction
      therapy in 51 high-risk AML patients. Diagnosis of AML in 22 patients was
      preceded by a myelodysplastic syndrome lasting more than six months; 8 of the 29
      de novo AML cases (28%) were refractory to previous chemotherapy, 9 (31%) were
      treated for early relapse, 12 (41%) presented poor prognostic factors at
      diagnosis. The median age was 64 (range 33-76) years and the FAB subtypes were
      the following: M0 3, M1 5, M2 28, M4 7, M5 8. Forty-eight per cent of patients
      showed poor prognosis chromosomal abnormalities. FLAG (24 patients) consisted of
      both fludarabine 30 mg/sqm over 30 minutes followed 4 hours later by Ara-C 2
      g/sqm over 4 hours (for 5 days) and G-CSF 300 micrograms/day administered 12
      hours before fludarabine, for a total of 5 doses. FLANG (27 patients) had a
      shorter duration (3 days), reduced Ara-C dosage (1 g/sqm) and administration of
      mitoxantrone (10 mg/sqm) at the end of Ara-C infusion. RESULTS: Recovery of both
      neutrophils (PMN > 0.5 x 10(9)/L) and platelets (Plt > 20 x 10(9)/L) required a
      median of 16 days from the end of therapy. Overall, 30 patients (59%) achieved
      CR, 6 (11%) PR and 10 (20%) were refractory; 5 (10%) experienced early death
      (cerebral hemorrhage or infection). The length of complete response ranged from 2
      to 26 months with a median follow-up of 8 months. De novo and secondary AML
      registered 62 and 54% CR rates, respectively. Eight out of 10 patients refractory
      to conventional schemes achieved CR (80%) but only 3 out of 10 treated for
      relapse obtained CR (30%). CONCLUSIONS: FLAG and FLANG showed similar activity
      and toxicity while proving to be highly effective and relatively well-tolerated
      treatments for high-risk de novo AML. Secondary leukemias seemed to be responsive
      as well, but the presence of an unfavorable karyotype alteration lowered the
      response rate.

PMID- 9009440
TI  - Peripheral blood stem cells for allogeneic transplantation. Recommendations from
      the GITMO 1996. Gruppo Italiano Trapianti di Midollo Osseo.
AB  - Allogeneic transplants with PBSC are rapidly expanding, but a number of problems
      concerning both donors and recipients are still unsolved. GITMO (Italian Bone
      Marrow Transplant Group) has established a committee for allogeneic PBSC
      transplants. We present here an analysis of the main aspects of this evolving
      area and suggest revised guidelines for the use of allogeneic PBSC
      transplantation.

PMID- 9009441
TI  - Autoimmune mediated thrombocytopenia associated with the use of interferon-alpha
      in chronic myeloid leukemia.
AB  - We report on two patients with Ph+ chronic myeloid leukemia (CML) in chronic
      phase who developed severe thrombocytopenia during treatment with interferon
      alpha 2A (IFN-alpha 2A). In both cases, we detected the presence of platelet
      associated antibodies (PAIg) by autoimmune flow cytometry. We postulated an
      immune mediated platelet destruction mechanism; corticosteroid therapy was
      employed and interferon therapy was withdrawn, resulting in an increase in
      platelet count and a reduction of PAIg. Our observation reports the detection of
      PAIg associated with IFN-alpha 2A therapy in CML and suggests that this
      immunomodulant drug could induce thrombocytopenia through a mechanism other than
      antiproliferation.

PMID- 9009442
TI  - Successful treatment of hepatic veno-occlusive disease in a peripheral blood
      progenitor cell transplant patient with a transjugular intrahepatic portosystemic
      stent-shunt (TIPS).
AB  - Hepatic veno-occlusive disease (VOD) is a common cause of morbidity and mortality
      after BMT. Although treatment of VOD is primarily supportive, some success has
      been obtained recently with fibrinolytic therapy. However, for critically ill
      patients liver transplantation may be the only therapeutic option. Nevertheless,
      this procedure is associated with high mortality and can only be performed in a
      minority of cases. The transjugular intrahepatic portosystemic stent-shunt (TIPS)
      is a non-surgical, side-to-side shunt consisting of an intraparenchymal duct
      between a main branch of the portal vein and a hepatic vein. In this report we
      describe a patient who underwent TIPS placement for severe VOD following
      autologous PBPC transplant. No complications developed and gradual improvement in
      clinical status and liver function was observed early after this therapy. Nine
      months after TIPS, the patient is asymptomatic with normal liver function. TIPS
      provides an interesting alternative to invasive therapies for patients with
      severe VOD after bone marrow or PBPC transplants.

PMID- 9009443
TI  - Factor V Leiden mutation investigated by amplification created restriction enzyme
      site (ACRES) in PNH patients with and without thrombosis.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired chronic hemolytic anemia
      characterized by intravascular hemolysis, often associated with neutropenia and
      thrombocytopenia. Venous thrombosis, including the Budd-Chiari syndrome, is one
      of the major complications of PNH, but not all PNH patients develop thrombosis.
      The basis for the high risk of thrombosis in PNH is not known. Recent reports
      have shown that Factor V Leiden mutation is a common cause of increased tendency
      to develop thrombosis. Fifty-six PNH patients were tested for Factor V Leiden
      mutation using Amplification Created Restriction Enzyme Site methods. PNH
      patients do not show an increased frequency of Factor V Leiden mutations.

PMID- 9009444
TI  - Congenital dyserythropoietic anemia type II: molecular basis and clinical
      aspects.
AB  - Congenital dyserythropoietic anemia of type II (CDA II) is a rare disorder,
      usually present in childhood, with a clinical picture of chronic anemia of mild
      to moderate degree, splenomegaly and intermittent or persistent jaundice. It is
      transmitted by autosomal recessive inheritance and is characterized by the
      presence of a large number of multinucleate and binucleate erythroblasts in the
      bone marrow and typical morphological abnormalities of the membrane of
      circulating erythrocytes. SDS-PAGE of red blood cell membrane proteins shows a
      narrower aspect and a faster migration of band 3 (anion exchange transporter).
      This aspect is consistent with decreased glycosylation of this protein. The
      genetic mutations responsible for the glycosylation defect in CDA II have not yet
      been identified. Analysis of carbohydrate structures and biochemical data
      indicate that the activity of either GnT II or alpha-Man II is reduced in
      different families, suggesting that the disease is genetically heterogeneous.
      Molecular cloning of the GnT II and alpha-Man II DNA sequences has allowed direct
      investigation of the genetic mutations underlying the glycosylation defect in CDA
      II patients to begin.

PMID- 9009445
TI  - Diamond-Blackfan anemia: a congenital defect in erythropoiesis.
AB  - Diamond-Blackfan anemia (DBA) is a congenital pure red blood cell aplasia
      diagnosed in the first year of life. Familiarity is apparent in 10% of patients,
      with all other cases being sporadic. Physical abnormalities are present in at
      least one third of patients, pointing to a defect in early embryo development.
      The main clinical sign is profound isolated anemia, with normal numbers and
      functioning of the other hemopoietic cells. Reticulocyte counts are very low.
      Bone marrow reflects defective erythropoiesis, showing a very low number of
      erythropoietic precursors and a reduction of BFU-E progenitor cells.
      Proliferation and differentiation of the other lineages are normal. The very high
      erythropoietin (EPO) levels are usually not proportionate to the level of anemia
      and reflect relative EPO insensitivity, which is also apparent in vitro.
      Conversely, erythroid progenitors from DBA patients also show a defective or
      incomplete response to other erythropoietic growth factors, such as IL-3 or IL-6.
      A significant response has been observed in vitro to stem cell factor in many,
      but not all patients. Many patients respond clinically to corticosteroids and
      some develop hematologic remissions, both after corticosteroids and
      spontaneously. Patients who do not respond to corticosteroids and those who have
      to discontinue treatment because of side effects must rely on chronic transfusion
      and are thus exposed to all its complications. Bone marrow transplantation has
      been performed in some individuals, usually with a successful outcome. This
      suggests a normal marrow microenvironment and rules out the hypothesis of
      defective stromal cell function. The variable clinical and biological patterns
      may be the expression of multiple etiologies or represent variable expressivity
      of a single genetic defect. Only identification of the responsible gene(s) will
      solve this question. Growth factors exerting an effect on erythropoiesis (and
      relative receptors) or transacting proteins which regulate their expression are
      likely candidates in the hunt for a causal gene.

PMID- 9009446
TI  - Stem cells and stem cell transplantation.
AB  - Stem cell transplantation (SCT) is an increasingly used therapeutic approach for
      the treatment of hematological and non-hematological disease of neoplastic and
      non-neoplastic origin. How the phenomena controlling blood cell production take
      place during SCT is still largely unclear. Increasing knowledge of stem cell
      biology, the availability of large amounts of stem cells due to mobilization
      techniques, as well as new developments in hematopoietic cell manipulation offer
      exciting experimental and therapeutical options in the field of SCT and will be
      reviewed here.

PMID- 9009447
TI  - Plasma cells and iron granules.

PMID- 9009448
TI  - Liver involvement during HCV infection in chronic lymphoproliferative diseases.

PMID- 9009449
TI  - Durable response to recombinant human erythropoietin in a patient with
      myelodysplastic syndrome.

PMID- 9009450
TI  - An emergency physician's perspective on death with dignity.

PMID- 9009451
TI  - Death with dignity: the case of physician-assisted suicide.

PMID- 9009452
TI  - Choosing to die.

PMID- 9009453
TI  - The elderly and disabled in Hawaii.

PMID- 9009454
TI  - Cultural issues in death and dying.
AB  - Although all of us experience death, not all of us think about death or respond
      to death the same way. This study begins to explore how cultural traditions,
      education, and tenure in Hawaii impact views of advanced directives, organ
      donation, suicide, and euthanasia. This information is useful to physicians who
      need to engage patients and families in discussions about death and end-of-life
      decision making.

PMID- 9009456
TI  - Euthanasia: murder or mercy?

PMID- 9009455
TI  - An attitudinal survey of euthanasia in Windward Oahu. A cross-sectional pilot
      study of four age groups.
AB  - Exploring the attitudes of 185 respondents toward euthanasia, this 1990 cross
      sectional pilot study utilized 12 survey questions addressing participants'
      demographic profiles and 18 focusing on: abortion; capital punishment;
      euthanasia; sterilization; and suicide. Cross-tabulation of structural,
      behavioral and attitudinal variables revealed age and education were the key
      factors in this study's finding that the greater a person's life experience, the
      more favorable one's attitude toward euthanasia.

PMID- 9009457
TI  - Why I do not believe in mercy-killing.

PMID- 9009458
TI  - Lethal aid--physician or lawyer-assisted suicide?
AB  - This article will provide information about the current legal status of the right
      of a person to request physician-assisted suicide. It will provide a background
      on two appellate court cases which dealt with this issue and the significance of
      the U.S. Supreme Court's intervention.

PMID- 9009459
TI  - St. Francis Hospice: Medicare and health care reform.
AB  - The St. Francis Hospice Program is symbolic of more than 100 years of Franciscan
      dedication to the people of Hawaii. Since Mother Marianne's arrival in November
      of 1883, the Sisters of the Third Franciscan Order Syracuse, New York have
      responded to the calling; "the charity of Christ impels us." It is through this
      calling that care and comfort for the terminally ill is a part of the mission of
      St. Francis Healthcare System. The magnificent spirit through which Hospice
      services have been made possible, is a reflection of God's great generosity to us
      throughout the years.

PMID- 9009460
TI  - Life and death in Hawaii: ethnic variations in life expectancy and mortality,
      1980 and 1990.
AB  - Life expectancy in Hawaii is among the highest in the nation. Past research,
      however, found significant ethnic differences in longevity. This study presents
      life expectancy estimations for 1980 and 1990, along with ethnic differences in
      mortality rates for specific causes of death. The findings suggest that ethnic
      differences continue, with Chinese and Japanese having the longest life
      expectancy and Native Hawaiians having the shortest.

PMID- 9009461
TI  - Models of physician-assisted dying.
AB  - Repeated surveys have shown that more than 70% of Americans support physician aid
      in dying for terminally ill mentally competent adults. Recent polls of physicians
      in Oregon and Michigan demonstrate majority support of those doctors for such a
      law while 25% of physicians surveyed in Washington admitted to already providing
      help. Models of how that would work have been spelled out in proposed legislation
      in the United States since 1988, other models come from the Northern Territory in
      Australia, from Holland, and from Jack Kevorkian's writing and actions as well as
      from other writers such as Dr Timothy Quill.

PMID- 9009462
TI  - A view of death and dying among the Chinese and Japanese.
AB  - The practices of medicine around the world have been fused into that of faith and
      religion. In serving our patients' need to accept death, physicians must also be
      sensitive to this underlying basic human concern as they prepare for this final
      journey. The Chinese and Japanese, reflecting their belief in Buddhism, perceive
      death as a natural part and an extension of life itself.

PMID- 9009464
TI  - Care of the dying at the John A. Burns School of Medicine University of Hawaii.

PMID- 9009463
TI  - Death with dignity: there's plenty more that we can do.
AB  - The medical profession has seen an accelerated interest in end of life decision
      making and terminal care. The growing need for attention in these areas requires
      more of the art of medicine--the human and compassionate side of medicine as
      opposed to the high technology side.

PMID- 9009465
TI  - To die or not to die--is that the question? Educating physicians about end-of
      life care.

PMID- 9009466
TI  - How Hawaii's doctors feel about physician-assisted suicide and euthanasia: an
      overview.
AB  - We polled, by questionnaire, all doctors and medical trainees in Hawaii (n =
      3,017) to determine their attitudes towards physician-assisted suicide,
      euthanasia and other end-of-life medical issues. One thousand and twenty-eight
      (34.1%) responded. Medical trainees did not differ significantly from practicing
      physicians. Only a minority of respondents (15.6%) were willing to assist a
      terminally-ill patient to commit suicide. An even smaller number (9.8) would
      perform active euthanasia. On the other hand, an overwhelming majority would
      withhold (97.6%) or withdraw (78.6%) life-support upon request. Most doctors
      (88.0%) were also willing to administer high doses of narcotics for pain relief,
      even if such therapy hastened death. About half the doctors felt that physician
      assisted suicide and active euthanasia may be justified under some circumstances,
      although most were unwilling to personally carry out these acts. Catholic,
      Filipino and Hawaiian/Polynesian doctors were statistically less likely to
      approve of or perform physician-assisted suicide or active euthanasia.

PMID- 9009467
TI  - Lives in the balance '96. A letter to members of Hemlock-Hawaii.

PMID- 9009469
TI  - Diagnosis and symptomatic treatment of migraine.
AB  - Migraine is a common, complex neurophysiologic headache disorder. Most
      migraineurs have neither been diagnosed by physicians nor effectively treated.
      The clinical diagnosis of migraine is based on headache characteristics and
      associated symptoms, particularly nausea and vomiting. Pharmacologic symptomatic
      treatment is aimed at reversing, aborting, or reducing pain and the accompanying
      symptoms of an attack. Individualization of therapy is essential in determining
      whether symptomatic and/or preventive treatment for migraine attacks are needed.
      The presence of nausea and vomiting must be considered in developing a treatment
      plan. The patient's priorities and preferences regarding therapy must be taken
      into account. The goals of symptomatic treatment are to relieve pain and the
      associated symptoms and to optimize the patient's ability to function normally.
      Multiple treatment strategies utilizing combinations of 5-hydroxytryptamine1 (5
      HT1) agonists (ergotamine tartrate [ET], sumatriptan, and dihydroergotamine
      [DHE]) with simple analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and
      opiates provide effective treatment for most attacks of moderate to severe
      migraine. Treatment strategies are based on the frequency, nature, and severity
      of attacks. Patients with intractable, acute migraine may require hospitalization
      and aggressive parenteral treatment. Wider use of currently available diagnostic
      criteria and symptomatic medications should improve the diagnosis and treatment
      of migraine.

PMID- 9009470
TI  - The pharmacology of ergotamine and dihydroergotamine.
AB  - The ergot alkaloids are a family of chemical entities that have many
      pharmacologic effects. Their diversity results from their interaction with
      multiple receptors, their variable receptor affinity and intrinsic activity, and
      their variable organ-specific receptor access. Ergotamine tartrate (ET) was one
      of the first ergot alkaloids to be isolated. Dihydroergotamine (DHE) is
      synthesized by reducing an unsaturated bond in ergotamine (E); this modification
      results in a changed pharmacologic profile. Dihydroergotamine exhibits greater
      alpha-adrenergic antagonist activity and much less potent arterial
      vasoconstriction and emetic potential. Both E and DHE are 5-HT1A, 5-HT1B, 5-HT1D,
      and 5-HT1F receptor agonists. The vasoconstrictor activities of these ergot
      compounds have long been believed to be the basis of their clinical effects, but
      recent evidence suggests that their antimigraine action may result in part from
      their inhibitory effects on neurogenic inflammation and neuronal transmission and
      not from vasoconstriction. Improvements in assay methodology have provided more
      accurate determination of the pharmacokinetics of E and DHE. The long duration of
      action appears to result from active metabolites and tight tissue binding.
      Intranasal (IN) administration of DHE delivers adequate plasma concentrations of
      the drug without the need for parenteral administration and should further expand
      its role in migraine pharmacotherapy.

PMID- 9009471
TI  - Dosing and administration of ergotamine tartrate and dihydroergotamine.
AB  - Ergotamine tartrate (ET) and dihydroergotamine (DHE) are effective therapies for
      migraine and cluster headache. Optimal management with these agents must take
      several factors into account, including headache type and severity, associated
      symptoms, side effect potential, choice of dosage forms, and appropriate dosing.
      Oral ET is most appropriate for slowly evolving migraine without early onset
      nausea and/or vomiting, or for treatment of cluster headaches. Delivery of ET via
      rectal suppository (available only in combination with caffeine) is the most
      effective form, especially for patients with severe, rapid onset migraine
      accompanied by nausea and/or vomiting. Dihydroergotamine offers numerous benefits
      compared to ET, including a lower incidence of nausea and vomiting and headache
      recurrence, and a lack of rebound headache. Dihydroergotamine can be administered
      at any time during a migraine attack, including the aura. Intravenous
      administration provides rapid peak plasma levels and is the most effective form
      when a rapid effect is desired or for patients with intractable severe headache
      (status migrainosus, transformed migraine, rebound headache) and cluster
      headache. Intramuscular administration is effective for moderate to severe
      migraine with or without nausea and vomiting in the clinic. Intranasal delivery
      of DHE has shown significant promise for effective and convenient therapy in
      acute migraine and may be especially useful in the presence of nausea and/or
      vomiting. When used appropriately, DHE and ET provide clinicians with highly
      effective therapeutic options in a range of useful dosage forms for patients with
      migraine or cluster headaches.

PMID- 9009472
TI  - Ergotamine tartrate and dihydroergotamine mesylate: safety profiles.
AB  - Ergotamine tartrate (ET) and dihydroergotamine mesylate (DHE) have been widely
      and effectively used in the treatment of migraine for many decades, although few
      randomized, controlled clinical trials have been conducted with these compounds.
      To compare their safety profiles, the world literature on the two agents was
      surveyed. The results are summarized, along with a critical analysis of the
      strengths and limitations of the various sources of safety data (in vitro
      research, animal studies, Phase I and II studies, controlled clinical trials, and
      postmarketing surveillance). Significant pharmacologic and safety differences
      exist between ET and DHE. Dihydroergotamine mesylate is a less potent arterial
      vasoconstrictor than ET, although nearly equipotent as a venoconstrictor. It is a
      more potent alpha-adrenergic antagonist, but is much less emetic, has less effect
      on the uterus, and is not associated with rebound headache. Adverse effects
      associated with ET (which are often due to excessive dosage and/or chronic usage)
      include nausea, acroparesthesia, ischemia, habituation and overuse headache, and,
      rarely, overt ergotism. Reports of serious adverse effects following recommended
      doses of DHE are rare. As with most antimigraine drugs, the most frequent adverse
      effect with intravenous (i.v.) DHE is nausea; however, following intramuscular
      (i.m.) or intranasal (IN) administration, the incidence of nausea is low and
      concomitant administration of an antiemetic is not needed. In patients without
      contraindications, both DHE and ET are safe and effective when used in
      recommended doses. Nearly 50 years of clinical experience without major safety
      problems allows a high level of confidence in their clinical use.

PMID- 9009473
TI  - Appropriate use of ergotamine tartrate and dihydroergotamine in the treatment of
      migraine: current perspectives.
AB  - Considerable uncertainty exists regarding the appropriate use and dose
      limitations for ergotamine tartrate (ET) and dihydroergotamine (DHE) for the
      treatment of migraine despite more than 50 years of clinical experience. The
      Quality Standards Subcommittee (QSS) of the American Academy of Neurology (AAN)
      appointed an advisory committee from experts in the Headache and Facial Pain
      Section. As their initial project, the committee elected to review the clinical
      literature on the appropriate use of these compounds in the treatment of
      migraine. Subsequently, clinical practice guidelines were formulated and recently
      published in Neurology. The Headache and Facial Plan Section and the QSS of the
      AAN were able to reach consensus on the basis of a thorough literature review and
      formulated practice parameters that describe and define the limits of ergot use,
      provide information on the oral and parenteral dosing of ET and DHE, and provide
      physicians with guidance to avoid ET overuse by patients. Because this project
      was completed prior to the availability of the intranasal (IN) formulation of
      DHE, intranasal DHE is not included in the practice parameter. Ergotamine
      tartrate and DHE were found to be safe and effective for the treatment of
      migraine as long as recommended dosages are not exceeded and high-risk patients
      such as those with uncontrolled hypertension, coronary or peripheral artery
      disease, thyrotoxicosis, or sepsis do not receive these compounds. In addition,
      the committee recommended restricting the use of ET in some instances because the
      overuse of ET has been associated with physical and psychological dependence
      resulting in predictable recurrent and/or rebound headaches, and subsequent
      severe withdrawal symptoms, including nausea, upon discontinuance of ET. None of
      these symptoms have been reported for DHE. These guidelines should help
      physicians provide optimal antimigraine therapy with these drugs.

PMID- 9009474
TI  - Blood transfusion services: blood safety in India.

PMID- 9009475
TI  - Argyrophilic nucleolar organizer regions in soft tissue tumors.
AB  - Argyrophilic nucleolar organizer region (AgNOR) staining was employed on 51
      apparently normal representative soft tissues, 53 benign soft tissues tumors and
      52 malignant soft tissue tumors with an aim to study the sensitivity and
      specificity of method in differentiating between the benign and malignant soft
      tissue tumors. The mean AgNORs count in apparently normal fibrous tissue was
      1.02, whereas it was 0.94 in adipose tissue, 1.14 in smooth muscle tissue, 1.115
      in skeletal muscle tissue, 1.025 in blood vessels endothelial lining cells and
      1.04 in nerve tissue. The mean AgNOR count was found to be higher in benign soft
      tissue tumors as compared to respective apparently normal soft tissue and was
      found to be statistically significant. The mean AgNOR count in soft tissue
      sarcomas was found to be higher as compared to both apparently normal soft tissue
      and benign soft tissue tumors. An increase AgNOR score in both benign and
      malignant soft tissue tumors as compared to apparently normal soft tissue
      indicates high proliferative activity. The neurofibrosarcoma showed low AgNOR
      count as compared to other soft tissues sarcomas. The fibrohistiocytic sarcoma,
      leiomyosarcoma and angiosarcoma showed a mean AgNOR score of 4 or more than four.
      The mean AgNOR score was found to increase with high grade of the tumor. The
      AgNOR staining is simple and useful method in estimating tumor cell proliferation
      thereby differentiating normal soft tissue from non-neoplastic proliferative
      growth, benign and malignant soft tissue tumors. It may help in differentiating
      fibromatosis from fibrosarcoma, dermatofibrosarcoma protuberans of low grade
      malignancy from high grade malignant fibrous histiocytoma and benign
      hemangiopericytoma from malignant hemangiopericytoma.

PMID- 9009476
TI  - Role of fine needle aspiration cytology in diagnosis of malignant scalp and
      underlying bone tumours.
AB  - Fine needle aspiration cytology (FNAC) was employed in 183 cases of clinically
      malignant scalp and underlying bone tumours from July, 1984 to December, 1994.
      The age of the patients ranged from 2 years to 89 years. There were 68 benign and
      115 malignant lesions. Only the malignant lesions are analysed in the present
      series. The cytological findings correlated with the histopathological analysis
      in 94.7% of cases. There was no false positive report. The cytological analysis
      helped the neurosurgeons to arrive to a quick pre-operative diagnosis which help
      early treatment avoiding open surgical biopsy in this vital area. Very scanty
      literature is available on FNAC of this region.

PMID- 9009477
TI  - Serum alpha-1-antitrypsin in ischemia and rheumatic heart diseases.
AB  - Tissue damage, inflammation and necrosis are hallmarks of myocardial infarction.
      In the present study significant elevations of serum alpha-1-antitrypsin were
      noted in coronary artery disease and angina cases. Interestingly chronic
      rheumatic heart disease which is also characterized by tissue injury.
      Inflammation revealed normal levels of serum alpha-1-antitrypsin. The level in
      chronic rheumatic heart disease was 3.37 +/- 0.57 mumol/mt/ml (control level was
      3.37 +/- 0.54 mumol/mt/ml). The corollary of these observations is that in heart
      diseases acute phase response in terms of enhanced levels of alpha-1-antitrypsin
      differ depending on the causative factors. Except chronic rheumatic heart
      disease, in all other stressful states studied there is (to a certain degree) an
      altered systemic homeostasis and haemostasis. On the other hand chronic rheumatic
      heart disease encompass certain amount of acute phase status in terms of tissue
      damage and inflammation does exist unaccompanied by altered systemic homeostasis
      and haemostasis. However, bacteriological etiologies predominate the triggered
      immune responses. It is hypothesised that serum alpha-1-antitrypsin enhancement
      will not occur even though acute phase state exists if specific immune responses
      are also a part of the disease manifestation.

PMID- 9009478
TI  - Evaluation of HBsAg carrier rate in acute viral hepatitis and high risk
      individuals using RPHA and ELISA.
AB  - A total of 600 individuals including 500 cases of hepatitis and 100 individuals
      at high risk for developing hepatitis were screened for hepatitis B surface
      antigen (HBsAg) using reverse passive haemagglutination (RPHA) and enzyme linked
      immunosorbent assay (ELISA). HBsAg carrier rate in clinically diagnosed cases of
      hepatitis was 38% and 32.4% by RPHA and ELISA respectively. In high risk
      individuals, the carrier rate was 14% by RPHA and 11% by ELISA. Taking ELISA as
      gold standard, RPHA showed 5.33% false positivity and 0.33% false negativity. The
      over all correlation between RPHA and ELISA was to the tune of 82.66%.

PMID- 9009479
TI  - Haematuria: glomerular or non-glomerular?
AB  - The standard urinary sediment of 80 consecutive patients with significant
      haematuria admitted at our hospital was examined for significantly dysmorphic red
      blood cells by 3 methods-1. Phase contrast microscopy, 2. Wright's staining of
      the urinary sediment, and 3. Simple light microscopy. The results of the study
      were compared with the final diagnosis reached in the ward and the sensitivity of
      the three methods was statistically compared. Our study conclusively proves that
      phase contrast microscopy is superior to light microscopy of plain or Wright's
      stained urinary sediment, with respect to both sensitivity and percentage of
      dysmorphism of the urinary red blood cells which can be detected.

PMID- 9009480
TI  - Adjuvant effect of DEAE-dextran and tetanus toxoid on whole cell heat inactivated
      phenol preserved typhoid vaccine.
AB  - Active mouse protection test (AMPT) and enzyme linked immunosorbent assay (ELISA)
      were used to determine the immunogenicity of whole cell typhoid vaccine when
      administered in conjunction with either tetanus toxoid (TT) or DEAE-Dextran (DD).
      Immunization of mice with whole cell typhoid vaccine showed enhanced potency
      either when administered in conjunction with TT or DD and values were
      statistically significant (p < 0.05) in comparison to conventional or standard
      typhoid vaccines. For ELISA, the mice were immunized with 2 different schedules,
      one in which a single dose of 0.25 ml subcutaneously (s/c) was administered and
      in another two doses of 0.25 ml each s/c, 14 days apart. In case of single dose
      schedule of immunization D vaccine (Whole cell typhoid + 5 mg/ml DD) showed
      significant increase of immune response (3.201 log10) as compared to plain
      vaccine (2.550 log10). Two dose schedule further increased the titres to 3.856
      log10. DD adjuvanted vaccine showed higher potency by AMPT as compared to the TT
      adjuvanted vaccine or plain vaccine. The present study clearly demonstrates that
      a single dose of 0.25 ml which is equivalent to half of the conventionally used
      single human dose of typhoid vaccine adjuvanted with DD can significantly improve
      the immunogenicity of the vaccine.

PMID- 9009482
TI  - Parathyroid cyst--a rare case report.
AB  - A rare case of parathyroid cyst in a forty six-year-old lady diagnosed clinically
      as solitary thyroid nodule is reported. An intra-operative diagnosis of
      parathyroid cyst was made which was confirmed histopathologically. The
      clinicopathologic aspects, diagnostic methods and treatment modalities of this
      unusual condition are briefly discussed.

PMID- 9009481
TI  - Metastatic carcinoma involving the testes.
AB  - Metastatic carcinoma to testis is an extremely rare but interesting phenomenon.
      Over a period of nineteen years 300 testicular tumors were diagnosed in our
      department, and of which 10 were metastatic carcinoma from other sites. Four of
      these patients (40%) presented as testicular lump of which two were already
      diagnosed cases of squamous cell carcinoma larynx and adenocarcinoma of lung, and
      two had occult primary in the kidney and colon. However six (60%) were detected
      incidentally in the orchiectomy done as a part of hormonal therapy for carcinoma
      prostate.

PMID- 9009483
TI  - Case report of intramuscular myxoma with review of literature.
AB  - This is a case report of a lady who presented with mass in the abdominal wall,
      clinically diagnosed as neurofibroma. On histological examination it was proven
      to be an intramuscular myxoma. Since it is rare it was thought relevant to report
      this case.

PMID- 9009484
TI  - Cytology of cystitis cystica glandularis of the bladder--a case report.
AB  - The cytologic findings of cystitis cystica glandularis--a form of proliferative
      cystitis which can be mistaken for a tumor clinically and radiologically have
      hardly been recorded. We describe a case of cystitis cystica where the bladder
      washings showed a spectrum of findings which were later corroborated on biopsy.

PMID- 9009485
TI  - Verruciform xanthoma--a case report.

PMID- 9009486
TI  - Tumoral calcinosis--a case report.

PMID- 9009487
TI  - Haemangiopericytoma of the nasal cavity.
AB  - Haemangiopericytoma of nose and paranasal sinuses is relatively uncommon tumour.
      It occurs in adults in sixth and seventh decades of life. In view of paucity of
      intranasal haemangiopericytoma old in Indian literature and young age of patient,
      we are reporting one case in 28-year-old female who presented with recurrent,
      profuse epistaxis.

PMID- 9009488
TI  - Peripheral odontogenic fibroma with chondroid differentiation.
AB  - An unusual case of peripheral odontogenic fibroma, presenting as a swelling on
      gingiva involving hard palate in a 3-year-old female child, is described. Even
      with cellular stroma and unencapsulation these tumors behave in a benign fashion.
      To the best of our knowledge, cartilagenous differentiation of stroma as observed
      in this case has not been reported in English literature so far.

PMID- 9009489
TI  - Primary synovial chondromatosis--a case report.
AB  - Synovial chondromatosis are rare tumours encountered in hip, knee and shoulder
      joints. Synovial chondromatosis at metatarso-phalangeal joints are still rarer.
      Herein is reported a case of primary synovial chondromatosis of
      metatarsophalangeal joint in 54-year-old male. A brief review of previous
      published articles has been dealt herewith.

PMID- 9009490
TI  - Xanthogranulomatous endometritis.

PMID- 9009491
TI  - Bilateral mammary metastasis of alveolar soft part sarcoma--a case report.

PMID- 9009492
TI  - Pleomorphic xanthoastrocytoma.
AB  - Pleomorphic xanthoastrocytoma is an unusual brain tumour of children with a
      favourable prognosis. The tumour takes origin from subpial astrocytes of the
      cerebral cortex. Histologically proliferation of spindle cells, mono and
      multinucleated giant cells containing lipid droplets and the absence of necrosis
      are distinctive features. Herein we report the morphological and
      immunophenotypical features of a case of pleomorphic xanthoastrocytoma.

PMID- 9009493
TI  - Current status of transfusion medicine in India.
AB  - A review of current scenario of transfusion medicine (TM) in India indicates an
      urgent need for restructuring the blood transfusion service (BTS). The BTS is
      hospital based with extreme variations in management and technology in different
      parts of the country. Compliance of quality assurance and good manufacturing
      practice is not ensured at all centres. Inspite of compulsory legislation, 34% of
      blood banks are yet unlicensed. Nearly 50% of 3 million units collected annually
      against a requirement of 6 million are estimated to be provided from paid blood
      sellers. Only 5% of voluntary donors are repeat donors. Complete testing of all
      donated blood is questionable due to operational problems. Only 40 centres are
      equipped to provide blood components. The shortage of blood is enhanced by
      inappropriate use of blood. Efficient clinical practice demands introduction of
      TM as a specialty.

PMID- 9009494
TI  - Rationale and strategy for utilization of available blood in transfusion practice
      -an overview.

PMID- 9009495
TI  - Adverse effects of colophony.
AB  - Regarding colophony, the use in industries, adverse effects, diagnosis,
      pathophysiology and control are reviewed. Colophony is an unhomogeneous mixture
      of resin acids as like abietic acid and neutral substances. Colophony is used
      everywhere, in industry, daily life and medical supplies. Soldering workers are
      exposed to the colophony fumes heated up to the temperature of soldering irons.
      The effects of exposure to colophony are classified into bronchial asthma and
      contact dermatitis. Colophony fumes cause bronchial asthma by its nonspecific
      irritation. Inhalation challenge test and repeated spirometry during working day
      may help the diagnosis of colophony induced asthma. Improvement of working
      environment for soldering and development of new flux instead of colophony will
      be necessary. A study on contact dermatitis revealed that colophony and its
      related compounds are one of major causes for contact dermatitis. Cases of
      dermatitis by depilatory agents used to remove hair from slaughtered swine, anti
      slipping cream for ballet shoes or resin for cello strings have been reported.
      Patch test may contribute to the diagnosis of dermatitis caused by colophony.

PMID- 9009496
TI  - Occupational factors, smoking habits and tobacco withdrawal symptoms among male
      Japanese employees.
AB  - The aim of the study is to know the effects of occupational factors and smoking
      habits on tobacco withdrawal symptoms among male Japanese employees. A total of
      2,862 male employees in a company in Japan completed questionnaires concerning
      tobacco withdrawal symptoms, occupational factors (occupation, shift work, work
      stress) and smoking habits. Data from 1,443 male ever-quitters were analyzed.
      Among male ever-quitters, 67% had ever experienced tobacco withdrawal symptoms.
      Significantly higher age-adjusted rates of tobacco withdrawal symptoms were found
      in those who experienced frequent exhaustion after work, current smokers, those
      who smoked 20 or more cigarettes per day, smoked for 20 years or longer and tried
      to quit smoking twice or more (p < 0.05). Multiple logistic regression analysis
      indicated that younger age, technical/clerical occupation, exhaustion after work,
      number of cigarettes smoked per day, duration of smoking, currently smoking and
      number of trials to quit smoking, were significantly associated with tobacco
      withdrawal symptoms (p < 0.05). It is suggested that younger age,
      technical/clerical occupation, exhaustion after work, number of cigarettes smoked
      and duration of smoking are risk factors of tobacco withdrawal symptoms in male
      Japanese employees.

PMID- 9009497
TI  - A study of complaints of fatigue by workers employed in Vietnamese factories with
      newly imported technology.
AB  - The aim was to study the actual situation of subjective fatigue among the
      Vietnamese workers in factories with newly imported technology. A cross-sectional
      study concerning working conditions and the fatigue complaints of 389 workers who
      are employed in 10 Vietnamese factories with newly imported technology, was
      conducted from August to September 1994. About 60% of the workers were satisfied
      with their current working conditions. Regarding occupational risks at the
      workplace, heat, dust and noise were identified as the three most dangerous
      risks. About 46% of the workers complained about the incompatibility of the
      machines and equipment they were using, which are too large for Vietnamese
      workers. One third of all workers felt that the work pace is too rapid. Seventeen
      percent of the workers considered their working conditions monotonous. Finally,
      among 150 female workers under 40 years old, 45 workers (30.0%) complained of
      irregularity of menstruation. Generally these problems were more common among
      workers in textile factories. The prevalence rate of subjective fatigue
      complaints was significantly increased after work in all 30 items. The fatigue
      level were substantially high among workers in textile factories. Female workers
      in this sector had a high prevalence rate of irregularity of menstruation. There
      were many problems observed in the Vietnamese factories with newly imported
      technology. Special consideration is required to improve the working conditions
      of female workers in the textile industry. Both the Vietnamese government and
      donor countries have to give special attention to the transfer of worker-friendly
      technology to Vietnam, in order to achieve sound economic development.

PMID- 9009498
TI  - The relationship between job stress and mental health at work.
AB  - In order to evaluate the relationship between job stress and mental health, a
      cross-sectional study was conducted using a questionnaire relating to
      demographics, subjective job stress and mental health state. The questionnaire
      consisted of a 30-item Japanese version of the General Health Questionnaire (GHQ)
      developed by Goldberg in addition to questions about subjective job stress, to
      measure mental health and job stress conditions, respectively. All subjects were
      employees of an electronic company in Japan. Among 782 workers, 763 workers
      responded to the questionnaire satisfactorily (response rate was 97.6%). People
      whose GHQ score was more than 7 were classified as having psychiatric problems,
      while the remaining respondents were considered as having no mental health
      problems. We employed a multiple logistic regression analysis to estimate the
      relationship between subjective job stress and mental health, adjusting for
      gender, age, marital state, familial stress, and physical health state.
      Subjective job stress was significantly associated with the state of mental
      health. In particular, the items of "too much trouble at work," "too much
      responsibility," "are not allowed to make mistakes," "poor relationship with
      superiors," and "cannot keep up with technology" were significantly related to
      mental health.

PMID- 9009499
TI  - Swell-preventing effect of intermittent exercise on lower leg during standing
      work.
AB  - This study investigated the effectiveness of several possible exercises for
      performance during standing work in order to prevent lower leg swelling and
      relieve subjective complaints. Volume changes in the lower leg were measured
      using bioelectrical impedance plethysmography in 13 healthy male subjects aged 23
      36 years. Subjective complaints of leg pain, leg dullness and whole body fatigue
      were also recorded. Measurements were performed at two-minute intervals during a
      one-hour period of standing with insertions of one-minute of exercise every 10
      min. The exercises were knee-bending, foot-stepping, walking, and heel-raising.
      The change rates of impedance over one hour were 2.2%, 4.0%, 4.6%, and 6.3%,
      respectively, indicating that leg volume was increased under all exercise
      conditions. Among exercises, the swell-preventing effect of knee-bending was
      strongest, and that of heel-raising was weakest. Heel-raising also yielded the
      highest number of subjective complaints. Knee-bending, which uses the thigh and
      calf muscles simultaneously, was considered the most effective for suppressing
      lower-leg swelling and minimizing subjective complaints.

PMID- 9009500
TI  - Effects of bright artificial light on subjective mood of shift work nurses.
AB  - The effects of bright artificial light on the subjective mental state of 10
      female nurses working shifts at a university hospital were assessed. We
      investigated two series of five consecutive workshifts rotations comprising one
      normal, two night and two evening shifts, using two self-administered rating
      scales. The subjects were exposed to artificial light, brighter than 3,000 lux,
      for a total of 30 min during each workshift of the second series, whereas they
      worked under normal lighting conditions (approximately 250 lux) during the first
      series. A three-way layout ANOVA, with repeated measures, revealed that bright
      light tended to improve eagerness and reduce tension, and improved vigor,
      eagerness, appetite and impairment (the latter only on the second night)
      significantly or nearly significantly during night, but not evening, shifts.
      These results suggest that bright artificial light affects the mental state of
      nurses during night, but not evening, shift work.

PMID- 9009501
TI  - Interaction of Illumination with noise on neuropsychological performance
      capability.
AB  - To determine the interaction effect of illumination with noise performance data
      were recorded from 20 male college student volunteers on a battery of
      neuropsychological tests comprising 'memory and search,' 'name and number
      checking,' 'Flanagan's eye-hand coordination' and 'digit symbol.' Each subject
      worked under two of the four combinations of illumination (low, 300 lux; high,
      500 lux) with quiet (60 dBA) and noise (100 dBA) conditions. A 2 x 2 analysis of
      variance was performed on the test scores. The accuracy of performance was found
      enhanced by high illumination in all the tests, but the speed of performance was
      impaired by noise. The interaction effect was significant, indicating the speed
      and efficiency of performance increasing while the accuracy of performance
      affected differently with high illumination under noise condition. However, the
      error of performance increased by noise under high illumination. Further
      investigation on a range of neuropsychological tests is suggested before the
      conclusions are drawn more firmly.

PMID- 9009502
TI  - An increase in noradrenaline excretion during prolonged mental task load.
AB  - To investigate the effects of prolonged mental work, urinary excretion of
      catecholamines and cortisol was measured in 18 human subjects from 9:30 to 17:00.
      On the "task day,' the subjects performed mental tasks during the morning (10:20
      11:45) and afternoon sessions (13:00-17:00), otherwise taking chair rest. On the
      "control day,' the subjects took chair rest in the afternoon after performing
      mental tasks in the morning. In the morning session, urinary excretion of
      adrenaline during mental work increased greatly compared to that before the
      mental work. Mental work in the afternoon session also caused a marked increase
      in adrenaline excretion compared to the rest level in the afternoon on the
      control day. Cortisol levels in the first hour of the afternoon mental work were
      significantly higher than those during the corresponding time on the control day.
      Urinary excretion of noradrenaline during mental work in the morning session only
      increased slightly compared to that before the mental work. In the afternoon
      session, however, noradrenaline excretion during mental work on the task day was
      markedly elevated compared to that during the rest condition at the corresponding
      time on the control day. These findings suggest that prolonged exposure to mental
      work, but not short-term mental work, produces a marked increase in noradrenaline
      excretion in human subjects.

PMID- 9009503
TI  - Toxicity of a low level of indium phosphide (InP) in rats after intratracheal
      instillation.
AB  - To clarify the instillation toxicity of low level of indium phosphide (InP), 0,
      1.2, 6.0 and 62.0 micrograms/kg body weight of InP particles were instilled
      intratracheally in male Fischer 344 rats, and the effects of InP were examined on
      the following day (day 1) and on the 8th day (day 8) after instillation. Indium
      was measured but not detected in the serum, liver, kidney, spleen, thymus and
      brain. Dose-related mild elevation of superoxide dismutase (SOD) activity and
      lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF) were
      found on day 1 without increases of inflammatory cells and total protein (TP) in
      BALF, which suggested the response of neutrophils and alveolar macrophages to
      instilled InP, and/or the manifestation of a very early stage of inflammation.
      Only in the 62.0 micrograms/kg-instilled group on day 8, were neutrophils,
      lymphocytes, TP, LDH, total phospholipid and total cholesterol in BALF increased,
      and desquamation of alveolar epithelial cells and amorphous exudate in alveolar
      lumen observed by histopathological examination. These results suggested that InP
      caused pulmonary inflammation and epithelial cell damage up to 8 days following
      instillation dose of 62.0 micrograms/kg, but that its effect was considered
      irrelevant at instillation doses of 6.0 micrograms/kg or below in rat.

PMID- 9009504
TI  - Lung lesions induced by intratracheal instillation of nickel fumes and
      nickeloxide powder in rats.
AB  - Acute and subacute lung toxicity of nickel fumes was examined by single and
      repeated intratracheal instillation of nickel fumes and Ni2O3 and NiO powders in
      the rat. LD50 of nickel fumes was estimated as 38.2 mg/kg body weight (b.w.)
      according to the method of Litchfield and Wilcoxon. Body weight gain was retarded
      as in the order of a single dose of 13.0 mg Ni2O3/kg > 14.3 mg nickel fumes/kg >
      1.4 mg Ni2O3/kg > 13.0 mg NiO/kg b.w. compared to controls. The histopathological
      changes in the lungs of the 14.3 mg nickel fumes/kg-dosed rats were milder than
      those induced by administration of 13.0 mg Ni2O3/kg but severer than those
      induced by administration of 1.4 mg Ni2O3/kg b.w. A single administration of NiO
      powder did not produce any histopathological effects on the lungs. The repeated
      administration of nickel fumes produced persistent edema and proteinosis in the
      alveoli. The nickel fumes, which were chemically composed of 97% of NiO and 3% of
      Ni2O3, were very fine particles about 5-10 nm in diameter, partly aggregated into
      larger particles and spherical particles about 0.6 micron in diameter. Solubility
      in distilled water and saline was in the order of nickel fumes > Ni2O3 powder > >
      NiO powder. It was suggested that a toxic Ni2O3 component and very fine particles
      of nickel fumes are involved in the acute lung toxicity of nickel fumes. The
      epithelial injury induced by reactive oxygen and hydroxy radicals, which would be
      produced during the process of conversion of Ni(III) to Ni(II) and phagocytosis
      of nickel fumes by macrophages and polymorphonuclear cells, are presumed to be
      involved in the pathogenesis of nickel fumes-induced lung lesion.

PMID- 9009505
TI  - Age-related changes in ventilatory and heart rate responses to acute ozone
      exposure in the conscious rat.
AB  - To evaluate the effect of age on toxicant-induced pulmonary and extrapulmonary
      changes, we examined the effect of inhalation exposure to oxone (O3) on the
      ventilatory and heart rate (HR) responses in 4-6 and 20-22-month-old male rats.
      The rats, chronically implanted with an electrocardiographic (ECG) electrodes,
      were placed in a head-out plethysmograph for continuous ventilatory measurements
      of tidal volume and breathing frequency. Simultaneous measurements of HR were
      also obtained. A 6-hr exposure of each rat to filtered air was followed 2 days
      later by a 5-hr exposure to 0.1 ppm O3, 5 days later by a 5-hr exposure to 0.3
      ppm O3 and 10 days later by a 5-hr exposure to 0.5 ppm O3. Each of the O3
      exposures was preceded by a 1-hr exposure to filtered air. Transient rapid
      shallow breathing with slightly increased HR appeared 1-2 min after the start of
      O3 exposure. It was suggested on the basis of the electroencephalographic (EEG)
      activity of the olfactory bulb that this transient response was mediated through
      olfactory sensation. Persistent rapid shallow breathing with a progressive
      decrease in HR occurred with a latent period of 1-2 hr. The last 90-min averaged
      values for relative minute ventilation tended to decrease with the increase in
      the level of exposure to O3 and these values for young rats were significantly
      lower than those for old rats. An exposure of young rats to 0.1 ppm O3 for
      shorter than 5 hr significantly decreased the tidal volume and HR and increased
      breathing frequency, but no significant changes were observed in old rats. There
      were no differences between young and old rats in non-observable-adverse-effect
      levels (NOAELs) for the O3-induced persistent ventilatory and HR responses, when
      the NOAELs were determined by exposure to 0.3 and 0.5 ppm O3. The present
      results, as well as the reported decrease in body temperature and blood pressure,
      suggested that the age-related changes in patterns and magnitude of the
      persistent rapid shallow breathing with a progressive decrease in HR are mediated
      through some age-related defense mechanism acting against O3 inhalation. The
      validity of the occupational exposure limit for O3 in workplaces was discussed in
      the light of the present findings.

PMID- 9009506
TI  - Mutagenicity of 2-bromopropane.
AB  - 2-Bromopropane (2BP, isopropyl bromide), a substitute for freon, has recently
      been suspected to be the causative chemical for the outbreak of some reproductive
      dysfunctions such as amenorrhea and oligospermia in workers who has been exposed
      to this solvent in an electronic factory. Bacterial mutation assays, chromosome
      aberration analysis in vitro, and micronucleus tests in vivo, were carried out to
      clarify the mutagenicity of 2BP. 2BP induced mutagenicity in Salmonella
      typhimurium TA100 with metabolic activation in a dose-dependant manner. 2BP
      induced mutagenicity in TA1535 as well, with or without metabolic activation.
      These observations indicated that 2BP induced the base-pair substitution type
      mutations in Salmonella strains. The chromosome aberration analysis showed
      negative results in Chinese hamster lung cells treated with different
      concentrations, ranging from 0.077 to 2.46 mg/ml for 6 h with metabolic
      activation and for 24 h without metabolic activation. The micronucleus
      frequencies were recorded by examining polychromatic erythrocytes in the bone
      marrows of rats which were intraperitoneally injected with 2BP for 28 days. There
      was no significant increase in the micronucleus frequencies at any of the
      different doses of 2BP (125 mg/ kg b.w./day, 250 mg/kg b.w./day, and 500 mg/kg
      b.w./day). However, in comparison to controls, there was a significant decrease
      in the percentage of polychromatic erythrocytes in the total number of
      erythrocytes. This suggests that there may be bone marrow depression in
      hematopoiesis at these dose levels of 2BP. Despite the dose levels which showed
      hematopoietic inhibition in the bone marrow, no micronucleus formation was
      induced.

PMID- 9009507
TI  - Induction of metallothionein-like cadmium-binding protein in the testis by oral
      cadmium administration in rats.
AB  - The possible induction of a metallothionein (MT)-like Cadmium (Cd) binding
      protein (MT-like Cd-BP) was investigated in rat testis after oral Cd
      administration. Male Wistar rats were given Cd by oral administration (20
      mgCd/kg, for 10 weeks), while the experimental controls were given Cd by
      intraperitoneal (i.p.) injection (2 mgCd/kg). Cd concentration increased in the
      testes after both administrations. However, much more Cd (about 4 times)
      accumulated in the tests of rats receiving oral Cd administration than in rats
      receiving Cd ip injection (experimental control). Meanwhile, MT-like Cd-BP
      decreased dramatically in the testes after Cd i.p. injection compared to that in
      the testes of untreated control rats. However, this testicular MT-like Cd-BP
      after oral Cd administration increased significantly up to about 1.4 times of the
      amount found in the testes of untreated control rats. Inhibition of glutathione S
      transferase (GST) activity and decreased glutathione (GSH) in the testes was not
      observed in rats after oral Cd administration. However, enzyme activity and GSH
      concentration were inhibited and decreased significantly in the testis by Cd
      toxicity after Cd i.p. injection. These results indicate that testicular MT-like
      Cd-BP, assumed to be MT and to be hardly inducible by Cd, is an inducible protein
      corresponding to increased Cd accumulation in the testis without damage by Cd
      toxicity after oral Cd administration.

PMID- 9009508
TI  - Induction of gonadal toxicity to male rats after chronic exposure to mancozeb.
AB  - Mancozeb-a fungicide of ethylenebisdithiocarbamate group was orally administered
      at doses of 500, 1,000 and 1,500 mg/kg body weight/day for 30, 90, 180 and 360
      days. Signs of toxicity mortality pattern and loss in body weight were observed
      in dose dependent manner. However, signs of intoxication and mortality pattern
      were more pronounced till the exposure of 90 days. A significant increase in
      testes and decrease in epididymis weight were associated with degeneration in
      seminiferous and epididymal tubules with loss of sperms. The decrease in gonadal
      acid phosphatase (ACP), succinic dehydrogenase (SDH) and increase in alkaline
      phosphatase (ALP), lactate dehydrogenase (LDH) activity were observed with
      increased serum cholesterol. Sialic acid and protein content of testis and
      epididymis were also decreased in dose dependent manner. The study has thus
      indicated marked biochemical and pathological changes in gonads of male rats
      after chronic exposure to mancozeb.

PMID- 9009509
TI  - Exposure of anesthesiologists to nitrous oxide during pediatric anesthesia.
AB  - Nitrous oxide (N2O) is one of the most common inhalation anesthetics in current
      anesthesiological practice. Even though artificial ventilation and active
      scavenging in operating theaters are employed in most of the modern hospitals,
      potential N2O contamination persists in regular anesthesia, particularly
      pediatric operation. In order to understand personal exposure during pediatric
      anesthesia, ambient monitoring for N2O exposure around the breathing zone of the
      anesthesiologist was conducted by a portable infra-red Miran 1B2
      spectrophotometer. The results demonstrated that general mask anesthesia
      generated greatest N2O contamination, with the mean time-weighted-average (TWA)
      concentrations of 85 +/- 48.4 (mean +/- S.D.) ppm in 12 cases. Initial mask
      induction followed by cuffed endotracheal incubation (6 cases) or intravenous
      induction followed by uncuffed endotracheal intubation (6 cases) also produced
      significant pollution to the workers, with the mean TWAs of 33.2 +/- 24.0 ppm and
      31.9 +/- 18.0 ppm respectively. These procedures provided exposure levels above
      the 25 ppm Recommended Exposure Limit (REL) of the National Institute of
      Occupational Safety and Health (NIOSH), U.S.A. Modification with intravenous
      induction followed with cuffed endotracheal intubation or mask general anesthesia
      provided with a ventilation hood diminished the contamination apparently, with
      the resulting mean TWAs of 11.0 +/- 4.7 ppm and 17.9 +/- 9.8 ppm in 7 and 5 cases
      respectively. The results indicated that excessive N2O exposure to
      anesthesiologists was not negligible during routine pediatric anesthesia.
      Significant reduction could be achieved via appropriate industrial modification.

PMID- 9009510
TI  - Estimation of CO exposure of road construction workers in tunnel.
AB  - Carbon monoxide (CO) level in three different tunnels in Boston area have been
      measured during rush hour periods, and expected CO exposure of construction
      workers who possibly work there was also estimated. CO levels in these tunnels
      have been measured at outside of a car running through the tunnels. The data
      collected in this study include vehicle speed, length of tunnels and traffic
      volume. In addition, structure of each tunnel was investigated. These data were
      used to estimate relationship between CO level and the distance of sampling
      points from entrance/exit of each tunnel. CO concentration in each tunnel was
      distributed in the range of 5 ppm-42 ppm, and linear relationship between CO
      concentration and distance from entrance/exit has been observed. This study had
      been held from April 1989 to May 1989 in Boston, MA, USA.

PMID- 9009511
TI  - Length-reduction method for man-made mineral fibers for biological experiments.
AB  - A simple fiber length-reduction method was developed to obtain a large amount of
      fiber samples with different length distributions for use in various biological
      experiments. This press method is only to press a raw fiber sample charged in a
      stainless cylinder at an adequate pressure, and is effective for man-made mineral
      fibers (MMMF) such as glass wool, rock wool and wool and refractory fibers
      (ceramic fibers, mullite fibers) and some brittle natural mineral fibers such as
      fibrous brucite and wollastonite. The mean fiber-length of man-made mineral
      fibers became shorter with the increase in the pressure applied without diameter
      change. We could obtain a length-reduced fiber sample with a suitable length
      distribution by this method. This press method is therefore a size-selective
      method able to produce a large amount of pulverized fiber sample depending on the
      press cylinder size for biological experiments. A very small amount of non
      fibrous particles with aspect ratios (length vs. diameter) of under 3 was seen in
      the pulverized fiber samples. To eliminate such non-fibrous particles as well as
      too long fibers from the sample, separation by sedimentation in water was
      somewhat effective.

PMID- 9009512
TI  - Design of a circular slot hood for a local exhaust system and its application to
      a mixing process for fine particles and organic solvents.
AB  - The characteristics of airflow (pressure loss and entry loss factor) were
      measured around a circular slot hood for its application to a local exhaust
      system. Centerline velocity, defined as the ratio of air velocity on the
      centerline of the slot hood to average slot face velocity, was found to be
      independent of the airflow rate. The relationship between the centerline velocity
      and the ratio of centerline distance to slot width was also found to be
      independent of the slot size. The empirical centerline velocity equation for the
      circular slot hood was thus constructed to design the local exhaust system.
      Recommended values for airflow rate into the circular slot hood and the average
      slot face velocity were found to be 20.14 m3/min and 8.55 m/sec, respectively.
      The optimum air velocity at a capture point was also found to be 5% of the
      average slot face velocity, i.e. 0.43 m/sec, and the effective ventilation with
      the hood was achieved with these values. The local exhaust system with the
      circular slot hood was installed for a mixing process of fine particles and
      organic solvents in a magnetic coating works. The effectiveness of the circular
      slot hood was confirmed by measuring the concentrations of airborne particles and
      vapors before and during the operation of the local exhaust system.

PMID- 9009513
TI  - Perspectives on the Tenth Revision of the International Classification of
      Diseases.

PMID- 9009514
TI  - Bridging individual, family and community care: a comprehensive treatment program
      for the chronic mentally ill.
AB  - For about 25 years an integrated individual-family-community program for chronic
      mentally ill patients has been implemented in Israel, mostly in the kibbutz
      setting. The treatment model is based on a combined professional and
      paraprofessional therapeutic team that designs a structured community program in
      the following areas: individual and family therapies, life-skills training,
      medication management, and enhancing performance in work and social spheres and
      in physical and leisure-time activities. This study reports on the treatment of
      124 psychiatric patients who have been followed-up for at least four years. Fifty
      percent of these chronically incapacitated patients achieved the goals of the
      community program and were found to be totally or greatly improved in terms of
      marked improvement of functioning and quality of life, resocialization, work
      stability and avoidance of rehospitalization. Fourteen percent of the patients
      were substantially improved, and 36% did not achieve the desired goal of
      satisfactory integration into community life. A case study that demonstrates the
      clinical application of the program is presented and the implications of the
      findings are discussed with respect to the community mental health service
      delivery system in Israel.

PMID- 9009515
TI  - Changes in attitudes of medical students towards psychiatry: an evaluation of a
      clerkship in psychiatry.
AB  - The attitudes to psychiatry of medical students before and after their clinical
      rotation in psychiatry were assessed during the course of the academic year 1989
      1990 by a questionnaire administered before and after the clerkship. Analysis of
      the data indicated that although there was no major shift in attitudes, the
      clerkship did succeed in improving clinical skills such as the capability for a
      better understanding of patients and the improvement of doctor-patient relations,
      as well as giving the student a more realistic approach to the diagnosis,
      treatment and prognosis of mentally ill patients.

PMID- 9009516
TI  - Characterization of patients refusing professional psychiatric treatment in a
      primary care clinic.
AB  - The purpose of this study was to characterize patients' refusal to meet a
      psychiatrist in a primary care clinic. Three hundred and seven patients were
      diagnosed as suffering from mental disorders: 57 of them were referred to the
      psychiatrist. Forty-seven patients who refused specialized psychiatric care
      formed the study group. The main measures were expressions, statements and
      reactions given by the patient for his/her refusal to undergo psychiatric care.
      Among nine types of expressions, statements and reactions, the most prevalent
      were: "I am afraid people would think I'm insane", "it might interfere with my
      social relationships and threaten my job," "I'm sufficiently strong to be able to
      deal with the problem myself," "it won't help, it won't solve my problems." We
      believe that a team approach involving the psychiatrist, social worker and the
      family physician should initiate and develop strategies for dealing with the
      stigma of psychiatric "treatment" as the refusal to undergo such treatment may
      result in the deterioration of these patients' mental condition.

PMID- 9009517
TI  - Assessment of insight in psychotic disorders.
AB  - This paper presents a selected review of the concept insight as regards
      recognition of the presence of illness among patients with psychotic disorders in
      general and with schizophrenia in particular and the development of new
      instruments for its assessment. Lack of insight appears to be a common pathway
      for different psychopathological processes and may have different meanings in
      different stages of the illness. Three major dimensions of the concept include:
      (1) awareness of having a mental illness; (2) the need for treatment; and (3)
      relabeling symptoms and signs as pathological and attributed to a mental illness.
      This complexity must be addressed by studies with a design using instruments
      which are appropriate to the research goals and carefully identify the stage of
      illness of the target population.

PMID- 9009518
TI  - The relation of Cotard's syndrome to delusional misidentification.
AB  - A case of Cotard's syndrome with face processing deficits is described. The
      phenomenology of Cotard's syndrome may be an expression of underlying visual
      processing deficits, including abnormalities in face perception processing.
      Phenomenologic and neurobiologic characteristics of this case are similar to
      those found among delusional misidentification syndromes. This similarity
      suggests areas for further study that may lead to a better understanding of the
      relation of phenomenology to neurobiology in Cotard's syndrome.

PMID- 9009519
TI  - Forensic psychiatry in Israel and Britain: some developing links.
AB  - There are growing links in forensic psychiatry between Israel and Britain. These
      can afford mutual benefit to forensic psychiatrists and other allied health
      professionals in both countries. As the specialty involves practice at times in
      conditions of security, there is a complex relationship between issues of
      treatment and those of public safety. It is essential to develop a firm academic
      and clinical base for the development of forensic psychiatry. These links between
      Britain and Israel need to be rooted in professional cooperation.

PMID- 9009520
TI  - Electro-encephalography spectral analysis of heroin addicts compared with
      abstainers and normal controls.
AB  - Previous studies have shown that opiates slow the EEG and, in high doses, reduce
      the threshold of seizure activity. The present work looks at computerized EEG
      analyses (in the Fast Fourier Transform-FFT-method) of heroin addicts, recent
      abstainers and normal controls, with the aim of comparison and delineation of
      group characteristics. Examinations of 60 taped EEG recordings were performed: 20
      subjects were current heroin users, 20 were recent abstainers and 20 were normal
      controls. Statistical analysis was performed for the relative frequency of wave
      bands. To amplify the known findings of slowing in heroin users, specific ratios
      were calculated: the alpha ratio (namely, the 8.0-9.5 Hz to 9.5-12.0 Hz ratio)
      and the delta to low alpha ratio. The specificity and sensitivity of the FFT
      method were evaluated through the use of discriminant analysis. The EEG was also
      recorded on conventional paper and evaluated by a neurologist. RESULTS: The
      addicts had a higher alpha ratio. The abstainers had a slowing of their alpha
      waves, a high incidence of delta waves and a delta to low alpha ratio that was
      relatively high. As a function of time from the beginning of abstinence, this
      ratio decreased. Abstainers for more than 80 days and controls had identical
      EEGs. The FFT method had 50% sensitivity for the addicts and 70% for the
      abstainers, while the specificity was 55%. In contrast, the neurologist's reading
      of the EEG had a very low sensitivity (25% for the addicts, 30% for the
      abstainers and 20% for the controls) and a 70% specificity.

PMID- 9009522
TI  - Hospitalism/institutionalization.

PMID- 9009521
TI  - Phenelzine as a possible treatment for depression in schizophrenic patients.

PMID- 9009523
TI  - Survival after AIDS diagnosis in South Carolina, 1982-1992.
AB  - The results of this study demonstrate that age, ethnicity, and AIDS-defining
      diagnosis are important predictors of survival time after AIDS diagnosis, and
      should be considered when planning treatment and services for people with AIDS.
      Future studies in states with large rural populations will be helpful in further
      understanding the natural history of the disease in areas outside the nation's
      major population centers. These could improve on the results of the present study
      by actively following up all cases to determine mortality status, collecting
      detailed clinical information on AIDS-defining diagnoses (with dates), collecting
      information on treatment of HIV infection and associated opportunistic
      infections, and evaluating service utilization. Monitoring survival trends over
      time remains an effective tool in evaluating the success of current efforts to
      provide treatment and services to people with AIDS.

PMID- 9009524
TI  - Abdominal aortic aneurysms, what's changing?

PMID- 9009525
TI  - Perceptions of a patients' bill of rights: a comparison of Massachusetts and
      South Carolina.

PMID- 9009526
TI  - The Golden Age of medical education: a letter to a classmate.

PMID- 9009527
TI  - Money and medicine.

PMID- 9009529
TI  - Taking stock.

PMID- 9009528
TI  - Samuel Eugene Harmon (1871-1935).

PMID- 9009530
TI  - Senior patients in the dental practice.

PMID- 9009531
TI  - Medical status, functional status and drug utilization patterns of a population
      of older dental patients in Winnipeg, Manitoba.
AB  - Despite the wealth of epidemiological studies that have evaluated the oral health
      status of older Canadian dental patients, comprehensive epidemiologic data on
      their medical status, functional status and drug utilization patterns are
      deficient. To address this deficiency, the authors evaluated 170 older dental
      patients (> or = 65 years, mean = 82 years, sex distribution = 77.1 per cent
      female, 22.9 per cent male) in Winnipeg, Manitoba. Study participants averaged
      five medical conditions per person (males = females). The most prevalent
      conditions were vision deficits, cardiovascular disorders and orthopedic
      problems. Functional assessment of the Activities of Daily Living revealed that
      study participants were essentially independent. Within the study population, 90
      per cent were taking at least one medication (mean = 2.8 drugs per person), most
      of which were analgesics, diuretics and gastrointestinal agents. Drug utilization
      rates were consistent with other studies that have evaluated prescribing patterns
      in community-dwelling older Canadian adults.

PMID- 9009532
TI  - Development of a senior-friendly dentists' booklet in Ottawa-Carleton.

PMID- 9009533
TI  - The Gluma bonding system: a clinical evaluation of its various components for the
      treatment of hypersensitive root dentin.
AB  - This study investigated the desensitizing effect of topically-applied Gluma on
      sensitive cervical erosion lesions. A total of 46 teeth exhibiting moderate to
      severe sensitivity to cold and instrumentation, in 15 patients, were included in
      the study. Mildly sensitive teeth and teeth with cervical caries lesions were
      excluded from the study. After each tooth was isolated with rubber dam,
      investigators applied cold air, as well as tactile stimuli using an explorer, and
      recorded the baseline responses. Nine of the 46 teeth then received Gluma primer
      only (group 1), 15 received cleanser followed by primer (group 2), 15 received
      cleanser followed by primer and sealer (group 3), and seven received a placebo
      (group 4). After two weeks, the teeth in group 4 were randomly placed in one of
      the other three groups. The responses of the teeth in each group to various
      stimuli were recorded immediately after the application of test materials, and
      subsequently at one week, two weeks, one month, three months, six months and one
      year. Statistical analysis indicates that the three treatment groups all showed
      significant differences compared to the untreated control group (p < .001). A
      reduction of sensitivity was noted immediately after primer, cleanser-primer, or
      cleanser-primer-sealer was applied. Treatment groups 2 and 3 demonstrated less
      sensitivity than group 1 (p = .02; p = .03, respectively). At the one-year
      recall, the observed order of treatment effectiveness by group was 2, 3, 1. In
      approximately 50 per cent of the teeth treated in the study, remission of
      sensitivity was seen after one year. All of the remaining teeth exhibited some
      relief of sensitivity. The treatments' success was found to be inversely
      proportional to the severity of the initial response.

PMID- 9009534
TI  - The interface between dentistry and medicine: a shared perspective.

PMID- 9009535
TI  - Investigating and restoring equivocal approximal lesions.

PMID- 9009536
TI  - Low-cost safe water for the world: a practical interim solution.
AB  - A very large segment of the world's population is without a microbiologically
      safe water supply. It is estimated that in Latin America more than 40% of the
      population is utilizing water of dubious quality for human consumption. This
      figure is probably even higher in Africa and areas of southeast Asia. Water used
      for drinking and food preparation can be an important route of transmission for
      many of the most widespread and debilitating of the diseases that afflict humans.
      The cholera pandemic which struck Latin America in January 1991, and has become
      endemic in many of the countries, continues to exemplify the public health
      significance of contaminated drinking water. Ideally, this neglected segment of
      the world's population should be served with piped water systems that provide a
      continuous supply of microbiologically safe water, but this would require such
      enormous investments of financial and human resources that it is not reasonable
      to expect that it will be accomplished. Interim practical measures to assure
      microbiologically safe water are necessary. The public health intervention to
      accomplish this is described in this paper and has an annual per family cost of
      which ranges between $1.50 and $4. It consists of providing individual households
      with one or preferably two suitable water containers in which to disinfect and
      store the essential quantities of water that need to be free of pathogens, with
      the containers of a design that will preclude recontamination of the contents and
      enable the production and distribution of the water disinfectants to be managed
      at the local level. It includes the necessary component of public education,
      promotion and involvement to establish the sustainability of the measures as a
      community-based endeavor. Investigation and demonstration projects are being
      carried out in II countries to determine and perfect and appropriate
      intervention, and it has been proven that it is economically, technically and
      socially feasible to assure microbiologically safe water for the world's
      population that is threatened by waterborne diseases. Carefully controlled
      microbiological analysis of the untreated and treated water shows that waterborne
      pathogens can be destroyed or inactivated, and carefully controlled
      epidemiological studies being carried out by the Centers for Disease Control and
      Prevention show that this intervention achieves considerable reduction in the
      incidence of water borne disease. It is recommended that all developing countries
      initiate programs to replicate the health measure described in this paper in
      order to test its validity and to adapt it to their local conditions.

PMID- 9009537
TI  - A critique of an evaluation of the impact of hospital bed closures in Winnipeg,
      Canada: lessons to be learned from evaluation research methods.
AB  - In the last few years, the continuing increases in health care expenditures have
      led to a call for greater accountability in health care and have spurred
      evaluative research into the area of health care policy. Yet the challenge has
      been to develop health care policy evaluations that maximize the rigor of the
      evaluation process within the constraints and limitations of evaluation milieus.
      This paper describes the principles of evaluation research and, using the example
      of a study evaluating the impact of hospital bed closures on community health
      status in Winnipeg, Canada, demonstrates the epistemological, methodological and
      interpretive problems that can occur when these principles are not followed. The
      conclusions are that studies which fail to outline the causal links between
      policy actions and outcomes, and use designs and methods which threaten internal
      and external validity, are limited in their abilities to elucidate the impact of
      health care policy changes.

PMID- 9009538
TI  - The development and prevention of cardiovascular disease risk factors:
      socioenvironmental influences.
AB  - In Third World countries, coronary heart disease is more frequent in the upper
      classes. In industrial countries such as the United States, Canada and the United
      Kingdom, there has been a widening social class difference in the opposite
      direction. Yet the social class differences have been largely ignored in the
      development of public health programs to prevent cardiovascular disease. This
      paper presents specific recommendations to correct this glaring defect, including
      giving priority to the reduction of risk factor prevalence among low-income blue
      collar and white collar workers; strengthening regulatory, taxation and other
      measures that directly impact all classes of the population; reversing the
      declining living standards of large segments of the U.S. population which result
      from current economic and political policy; and greatly expanding the resources
      available for public health programs from their grossly inadequate level.

PMID- 9009539
TI  - The economic costs of cardiovascular disease mortality in California, 1991:
      implications for public health policy.
AB  - This study estimates costs of lost productivity in California due to
      cardiovascular disease (CVD) mortality. Death records were used to calculate
      mortality losses including the number of deaths due to CVD, Years of Potential
      Life Lost (YPLL), and the value of productivity losses. In 1991 there was $5.3
      billion in lost productivity due to mortality caused by diseases of the heart and
      over one billion dollars in lost productivity due to cerebrovascular disease
      mortality. Racial/ethnic differences in YPLL are pronounced, which likely reflect
      the long-standing inverse association between CVD mortality and socioeconomic
      status that has been documented in a variety of populations worldwide. While it
      is important to effectively retain or develop low risk behaviors in populations,
      it is equally important to reduce barriers engendered by social, economic, and
      political patterns that inhibit the compression of CVD morbidity and mortality.

PMID- 9009540
TI  - Local health department effectiveness in addressing the core functions of public
      health: essential ingredients.
AB  - OBJECTIVES: Objective 8.14 of the U.S. Healthy People 2000 objectives calls for
      90% of the population to be served by a local health department (LHD) which is
      effectively carrying out the core functions of public health (assessment, policy
      development, assurance). This study seeks to describe the structural and service
      characteristics of an effective LHD. METHODS: Data from a 1993 national random
      sample survey of LHD practice were merged with data from the 1992-1993 National
      Association of Country and City Health Officials (NACCHO) profile of local health
      agencies. Using a definition of effectiveness related to the core functions of
      public health, the correlates of effectiveness were examined for 264 health
      departments in the matched sample. RESULTS: Effectiveness of local health
      agencies was not related to jurisdiction size of type. Inputs (structural
      factors) associated with effectiveness included having a full-time agency head, a
      larger budget derived from a greater number of funding sources, and a larger
      number of staff. With respect to outputs (services), effective health departments
      were also more likely to provide a greater number of services directly,
      particularly personal preventive and treatment services. CONCLUSIONS: Only a few
      inputs are correlated with core-function related effectiveness. However, a
      profile of an effective health department emerges. Effective LHDs appear more
      likely to have full-time leadership which is able to tap diverse funding sources
      to provide the mix and match of community and personal prevention and treatment
      services needed to address community needs and improve the public's health.

PMID- 9009541
TI  - Role of medical education in health care reform.
AB  - Health care reform will have great impact on the podiatric physician as the
      podiatric medical profession continues to integrate into the general medical
      community. The role of medical education in addressing five major issues that
      affect health care reform is explored. These issues include specialization,
      economics, continuous quality improvement, ethics, and fraud.

PMID- 9009542
TI  - Comparison of Viscoped and PORON for painful submetatarsal hyperkeratotic
      lesions.
AB  - A clinical study was performed to evaluate the efficacy of the Viscoped Insole as
      compared with an 1/8-inch PORON medical materials insole in the treatment of
      lesser submetatarsal hyperkeratotic callosities. Thirty-five patients, ranging in
      age from 23 through 61 years (average 42 years) were randomly divided into three
      groups. All three groups initially had debridement of their submetatarsal
      callosities. In addition to the debridement, the first group (16 patients) wore a
      Viscoped Insole for 4 weeks. The patients in the second group wore a PORON insole
      for 4 weeks. The third group did not receive an insole after their debridement
      and served as the control. There was a significant improvement in the Viscoped
      group and the PORON group versus the control group (x2 = 40; p < 0.01) as
      measured by the foot function index. Insole therapy combined with debridement for
      submetatarsal hyperkeratoses is more effective than debridement alone.

PMID- 9009543
TI  - Evaluation of magnetic foil and PPT Insoles in the treatment of heel pain.
AB  - The effect of a magnetic foil placed in the PPT/Rx Firm Molded Insole on the
      relief of heel pain was determined using the foot function index. Nineteen
      patients wore the PPT/Rx Firm Molded Insoles with the magnetic foil for 4 weeks
      and 15 patients wore the same PPT/Rx Firm Molded Insole with no magnetic foil for
      the same time. Approximately 60% of patients in both groups reported improvement.
      There was also no significant difference in the improvement between the magnetic
      foil group and the PPT/Rx Firm Molded Insole group in their scores on the post
      treatment foot function index. These results suggest that the PPT/Rx Firm Molded
      Insole alone was effective in treating heel pain after only 4 weeks. The magnetic
      foil offered no advantage over the plain insole.

PMID- 9009544
TI  - Effect of persistent toe walking on ankle equinus. Analysis of 60 idiopathic toe
      walkers.
AB  - Sixty idiopathic toe walkers (age range 1 to 15 years) were evaluated to
      determine the natural history of toe-to-toe gait and the relationship between the
      range of ankle dorsiflexion and increasing age. The majority of toe walkers had a
      normal birth weight (average 7.06 pounds), walked on time (average 11.14 months),
      began toe walking immediately (87%), stood plantigrade (90%), were able to
      demonstrate a heel-toe gait (88%), and toe walked intermittently (68%). Forty-six
      percent of all toe walkers were found to have 0 degree or less of passive ankle
      dorsiflexion. Equinus toe walkers (mean dorsiflexion -5.2 degrees) had
      significantly less dorsiflexion than the remaining toe walkers (mean dorsiflexion
      16.9 degrees; p < 0.01). An average of 12 degrees of dorsiflexion was resent in
      the 1-to 2-year age group, which gradually diminished to -4 degrees in the 6- to
      15-year age group. It appears that there may be a relationship between persistent
      toe walking and the development of ankle equinus in some children and therefore
      interventions should be considered to inhibit the toe walking progression.

PMID- 9009545
TI  - Orthotic variants.
AB  - When patients present with problems for which existing devices are not adequate,
      research is stimulated. However, new methods and devices must improve on the
      older versions and should not result in variation that is less effective than the
      original versions. Variants less effective than the originals will be discussed
      with illustrative examples. Orthoses, prostheses, and pressure-reduction
      techniques for the diabetic foot will be considered.

PMID- 9009546
TI  - Reappraisal of the negative impression cast and the subtalar joint neutral
      position.
AB  - For many years, podiatric physicians have been casting orthotic devices with the
      foot placed in the subtalar joint neutral position based on work by Root et al.
      Recent research pertaining to the subtalar joint neutral position during the gait
      cycle is in disagreement with the theory of Root et al and the inverted subtalar
      joint neutral casting technique. The current research and a historical
      perspective of casting techniques will be reviewed to help clarify terminology
      and to decipher the relationship between the rearfoot position during the gait
      cycle and casting technique.

PMID- 9009548
TI  - Physician practice evaluations--Do the exams never stop?

PMID- 9009547
TI  - Lower extremity injuries at the New York City Marathon.
AB  - The purpose of this study was to determine the type and frequency of lower
      extremity running injuries incurred by athletes participating in the New York
      City Marathon. A survey was conducted of 265 athletes presenting to medical
      stations for podiatric care during the 1994 New York City Marathon. The results
      of the survey indicated that the most common injuries occurring in marathon
      runners were corns, calluses, blisters, muscle cramps, acute knee and ankle
      injuries, plantar fasciitis, and metatarsalgia. An inverse relationship was
      observed between the number of miles trained per week and the number of injuries.
      These findings are consistent with long-term studies of running injuries.

PMID- 9009549
TI  - The patient's right to know--full disclosure laws are necessary for patients and
      physicians.

PMID- 9009550
TI  - Arkansas physicians in the AMA. Your representatives to medicine's strongest
      voice.

PMID- 9009551
TI  - Lidocaine-induced cardiac asystole.

PMID- 9009552
TI  - Radiological case of the month. Calcified uterine leimyomata.

PMID- 9009553
TI  - Health care of adolescents.

PMID- 9009554
TI  - Variation in the pattern of bacterial infection in patients with sickle cell
      disease requiring admission.
AB  - In order to determine the prevalence and pattern of bacterial infections in
      children with sickle cell disease (SCD) admitted with acute illness, a
      prospective study of 304 sicklers aged 3 months to 15 years was carried out over
      1 year in the emergency pediatric unit of ABU Teaching Hospital Kaduma. Initial
      blood and urine cultures were obtained in all cases and other cultures were
      performed as determined by the patients' clinical condition. Almost 60 per cent
      of the patients had positive bacterial cultures with gram negative organisms
      accounting for 55 per cent of them, but the single most predominant organism
      isolated was Staphylococcus aureus. Of note was the strikingly low isolation rate
      of Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitides.
      Possible reasons for this difference from the majority of reports from the
      western World are advanced and the implications discussed, especially as regards
      vaccination programmes in sickle cell disease and initial antibiotic treatment of
      those with acute illness.

PMID- 9009555
TI  - Throat microflora in breastfed and formula-fed infants.
AB  - Most bacterial infections are caused by organisms that are already colonizing the
      host, and these infections commonly originate at site of the gastrointestinal and
      respiratory tracts. However, little attention has been focused on the indigenous
      microflora of the respiratory tract in the infant. We studied the throat
      microflora of healthy breastfed and formula-fed infants. The incidence of
      pathogenic bacterial isolation from breastfed infants (1 out of 23) was lower
      relative to infants fed formula (5 out 14). The dominant bacteria in the throat
      flora isolated in both breastfed and formula-fed infants were alpha-haemolytic
      Streptococcus and gamma Streptococcus. These results suggest that breastmilk may
      be effcacious in preventing the growth of pathogenic bacteria in the throat.

PMID- 9009556
TI  - In vitro activity of human milk against the causative organisms of ophthalmia
      neonatorum in Benin City, Nigeria.
AB  - The aim of the study was to evaluate the in vitro activity of term human milk on
      the organisms of Ophthalmia neonatorum and was a prospective study of consecutive
      neonates with the organism. The study was undertaken in a special care baby
      unit/lying-in ward in Benin City, Nigeria, and consisted of 22 neonates with
      ophthalmia neonatorum. Bacterial organisms grown on blood agar, were obtained
      from eye swabs of neonates with ophthalmia neonatorum. Inoculated isolates were
      incubated with known antibiotic discs, term colostrum, and mature milk. Bacteria
      were isolated in 77 per cent (17/22) of the neonatal eye swabs, 59 per cent of
      which were Staphylococcus aureus and 41 per cent coliform organisms. Sensitivity
      of Staphylococcus aureus to gentamicin was 100 per cent and for coliform
      organisms 42 per cent. The sensitivity of Staphylococcus aureus to term colostrum
      was 50 per cent and to mature milk 0. Coliform organisms had a sensitivity of 57
      per cent to colostrum and 28 per cent to mature milk. The zone of inhibition of
      colostrum against Staphylococcus aureus and coliform organisms was between 3 and
      5 mm, while for mature milk, there was partial or no inhibition, respectively, to
      coliform organisms and Staphylococcus aureus. The mean duration of inhibition was
      6 hours for colostrum and 3 hours for mature milk. Colostrum has about half the
      in vitro inhibitory activity of gentamicin (recommended as a first line topical
      agent, based on the bacteriological sensitivity of this study) against
      Staphylococcus aureus and coliform organisms. The inhibitory activity of
      colostrum is > or = 50 per cent against Staphylococcus aureus and coliform
      organisms for a mean duration of 6 hours. Mature milk had no inhibitory activity
      against Staphylococcus aureus and only 28 per cent inhibition, for a mean
      duration of 3 hours to coliform organisms.

PMID- 9009557
TI  - Recombinant human erythropoietin trial in thalassemia intermedia.
AB  - It has been shown that high doses of human recombinant erythropoietin (r epo)
      increase haemoglobin levels by augmentation of F-cells, and Hb-F production in
      animal models and in human trials. In this study, r epo was used in patients with
      beta thalassemia intermedia. Our purpose was to improve haemoglobin levels by at
      least 2 g and maintain an average level between 10 and 12 g/dl. Ten patients aged
      6-29 years (mean 14 +/- 7.6 years) with thalassemia intermedia were treated with
      r epo. It was given subcutaneously in rising doses from 500 to 1000 U/kg three
      times weekly for 3 months. During r epo therapy eight cases (80 per cent) showed
      an increase in haemoglobin, haematocrit, and reticulocyte levels, and an increase
      of at least 2 g of haemoglobin was obtained. Blood transfusion was not needed
      during the study except in one case. Five cases (50 per cent) improved life
      quality with therapy. Hb levels of all patients returned to baseline values over
      1 or 2 months after r epo was discontinued. There was no significant change in
      absolute Hb-F, F-cells, and ferritin levels during treatment. Generally, the drug
      was well tolerated. No patient had hypertension. Recombinant erythropoietin seems
      to be an effective treatment for anaemia of beta-thalassemia intermedia, but
      longer term randomized trials are needed especially in patients with beta
      thalassemia major.

PMID- 9009558
TI  - Maternity care for Hispanic women who cross to the United States side of the
      Mexico border.
AB  - Medical chart abstracts and interviews were conducted among 587 Hispanic women
      within the first 72 hours following childbirth in any of five hospitals in San
      Diego County in 1991-1992. Demographic and maternal/infant obstetrical outcome
      data from 83 women who admitted that they had crossed the US/ Mexico Border to
      receive reproductive health services were compared with data from women who did
      not cross the Border. Border crossers were younger, less conversant in English,
      and more financially vulnerable. Several barriers existed for women in both
      groups that prevented entering and remaining within prenatal care programmes.
      Outcome data were favorable despite these adverse risk factors.

PMID- 9009559
TI  - Trends in intra-uterine growth of single live births in southern India.
AB  - Trends in intra-uterine growth (IUG) of newborns from 1969-1973 to 1989-1993 were
      studied among rural and urban communities. Yerushalmy's five group classification
      of IUG was used. The percent preterm low birthweight (LBW) declined from 7 to 3
      in rural and from 5 to 2 in urban areas. The percent of newborns with retardation
      of IUG declined from 20 to 11 in rural and from 13 to 8 in urban areas. Possible
      factors contributing to such changes are discussed.

PMID- 9009560
TI  - Death in a diarrhoeal cohort of infants and young children soon after discharge
      from hospital: risk factors and causes by verbal autopsy.
AB  - Assessing mortality pattern of children after discharge from hospital is
      important to guide appropriate management policy. We studied young children aged
      1-23 months, who were discharged from an urban Diarrhoea Treatment Hospital.
      Children were enrolled on discharge from the hospital, and followed at home after
      6 and 12 weeks to assess post-discharge mortality. Of 500 children, 427 were
      available for evaluation at home 6 weeks after discharge. The median age of the
      children was eight months, 77 per cent of whom were less than 12 months of age.
      Of the 427 children, 30 (7 per cent) died within 6 weeks and two died within 12
      weeks of discharge from hospital. The median survival time of the deceased was 11
      days. Children less than 6 months of age had a five times greater risk of death
      compared with those aged 6 months or older. Malnutrition, non-breastfeeding, and
      lack of immunization were important risk factors for death. As ascertained by
      verbal autopsy, the underlying causes of death were respiratory diseases and
      watery diarrhoea. Malnutrition and low birth weight were the main associated
      causes. Hospitalized children, especially young infants, should be given special
      attention and need to be followed preferably within a week of discharge.

PMID- 9009561
TI  - Congenital hypothyroidism: increased incidence in Najran province, Saudi Arabia.
AB  - Neonatal screening for congenital hypothyroidism using cord serum thyroid
      stimulating hormone (TSH) was initiated in Najran health region in September
      1990. A total of 30810 newborn infants were screened by April 1995. Of the 24
      infants with abnormal thyroid function tests on recall, 22 had permanent primary
      congenital hypothyroidism (incidence; 1:1400) and in two male siblings transient
      congenital hypothyroidism (incidence; 1:15400) was proved on follow-up. There was
      a significantly higher incidence of dyshormonogenesis. Eight (57 per cent) of the
      14 infants who were adequately studied thyroid scan revealed ectopic glands with
      increased 99mTc uptake, while thyroid ectopy and aplasia were present only in
      three (22 per cent) infants each. Furthermore, goiter was evident clinically in
      two other patients.

PMID- 9009562
TI  - Hepatitis B virus infection in pregnant women and its transmission to infants.
AB  - HBsAg was screened by Reverse Passive Haemagglutination Test (RPHA) and was
      confirmed by ELISA test in 157 pregnant females and their newborns. Anti-HBc and
      IgM anti-HBc was done in these cases by enzyme immuno-assay. The overall
      prevalence of HBsAg in mothers was 16 out of 157 (10 per cent) and in cord blood
      of newborns 5 per cent. The transplacental transmission was found in eight of 16
      (50 per cent) HBsAg positive mothers. Anti-HBc was present in 12 out of 16 (75
      per cent) HBsAg positive mothers and, of these, seven (58 per cent) neonates
      acquired HBsAg infection. IgM anti-HBc was present in seven out of eight (88 per
      cent) HBsAg positive neonates, suggesting active in utero infection. Fourteen out
      of 16 (88 per cent) neonates born to HBsAg positive mothers were alive and
      healthy, one was stillborn and one had a congenital anomaly.

PMID- 9009563
TI  - Risk factors associated with retinopathy of prematurity: a study from Oman.
AB  - In a prospective study at Sultan Qaboos University Hospital, out of 73 premature
      infants screened for retinopathy of prematurity (ROP), 25 (34 per cent) developed
      the disease. Nine significant risk factors were found to be associated with the
      development of ROP. These factors were lower birth weight, shorter gestational
      age, apnoea, top-up blood transfusion, mechanical ventilation, receiving sodium
      bicarbonate for correction of metabolic acidosis, total parenteral nutrition,
      intraventricular haemorrhage, and sepsis. However, with stepwise logistic
      regression analysis, only birth weight, gestational age, and total parenteral
      nutrition were found to be independently associated with the development of ROP.
      The severity of ROP was significantly inversely proportional to both birth weight
      and gestational age. The tendency for the association of some risk factors to
      disappear when subjected to more stringent analysis (logistic regression)
      suggests that this association is more likely to be due to the length of
      treatment (particularly oxygen exposure and mechanical ventilation) and the
      overall severity of initial illness.

PMID- 9009564
TI  - Use of HIV-1 specific immunoglobulin G3 as a serological marker of vertical
      transmission.
AB  - The objective of the study was to indicate HIV infection in infants. The patients
      were part of a longitudinal cohort of 43 infants born to HIV seropositive
      mothers. A modified Genelavia EIA primarily directed against HIV envelope
      proteins was used. An alkaline phosphatase labelled IgG3 conjugate was
      substituted in place of the kit conjugate. HIV specific IgG3 clearance was
      optimal at 6 months, whilst HIV total antibody was reliable only from age 12
      months onwards. At 6 months no detectable IgG3 were found in 91 per cent of
      uninfected infants where more of these infants had reduced their total HIV
      antibody titres at the same period. We confirm that HIV specific IgG3 measurement
      is a reliable and cost effective means of identifying HIV infected infants from 6
      months of age onwards.

PMID- 9009565
TI  - Interleukin-1-beta, tumour necrosis factor-alpha, islet-cell antibody, and
      insulin secretion in children with thalassemia major on long-term blood
      transfusion.
AB  - In vitro, cytokines like interleukin-1-beta (IL-1-B) and tumour necrosis factor
      alpha (TNF-A) inhibit insulin release and can destroy islet B-cells. We measured
      blood levels of IL-1-B, TNF-A, and islet cell antibody (ICA) in 20 children with
      IDDM, 20 of their non-diabetic siblings, 20 children with thalassemia major on
      long-term hypertransfusion therapy and iron chelation, and 10 normal age-matched
      children. In the non-diabetic and thalassemic children we investigated the early
      phase of insulin release after i.v. glucose (0.5 g/kg, 30 per cent solution) and
      evaluated tolerance to oral glucose (1.75 g/ kg). Circulating IL-1-B and TNF-A
      concentrations were significantly higher in IDDM-siblings (33.7 +/- 12.7 pg/ml
      and 655 +/- 165 pg/ml, respectively) v. normal children (21.1 +/- 6.4 pg/ml and
      383 +/- 122 pg/ml, respectively). Thalassemic children had no detectable
      circulating ICA. The prevalence of ICA was 30 per cent in children with IDDM and
      60 per cent of their siblings. Impaired oral glucose tolerance was detected in
      five children with thalassemia (25 per cent), but in none of the IDDM-siblings.
      The early phase of insulin release was significantly depressed in thalassemic
      children (peak insulin = 29.2 +/- 5.1 mIU/ml) v. normal children (52.3 +/- 9.5
      mIU/ml) and IDDM-siblings (45.3 +/- 12.4 mIU/ml). It appears that thalassemic
      children had significantly decreased insulin secretion and impaired glucose
      tolerance, however, the mechanism of B-cell dysfunction is not mediated by ICA
      nor by cytokines.

PMID- 9009566
TI  - Validation study of a verbal autopsy method for causes of childhood mortality in
      Namibia.
AB  - Verbal autopsy uses a caretaker interview to determine the cause of death. We
      conducted a study of the major causes of child death in Namibia to determine the
      validity of this method. A questionnaire, including signs and symptoms of the
      diagnoses of interest was administered to the caretaker in 135 deaths of children
      < 5 years old who were identified from hospital records. The 243 diagnoses
      included malnutrition (77), diarrhoea (73), pneumonia (36), malaria (33), and
      measles (24). Sensitivity and specificity of various algorithms of reported signs
      and symptoms were compared to the medical diagnoses. An algorithm for
      malnutrition (very thin or swelling) had 73 per cent sensitivity and 76 per cent
      specificity. An algorithm for cerebral malaria (fever, loss of consciousness or
      convulsion) had 72 per cent sensitivity and 85 per cent specificity, while for
      all malaria deaths the same algorithm had low sensitivity (45 per cent) and high
      specificity (87 per cent). For diarrhoea, loose or liquid stools had high
      sensitivity (89 per cent), but low specificity (61 per cent). Cough with dyspnoea
      or tachypnoea had 72 per cent sensitivity and 64 per cent specificity. An
      algorithm for measles (age > or = 120 days, rash) had 71 per cent sensitivity and
      85 per cent specificity. The study results suggest verbal autopsy data can be
      useful to ascertain the leading causes of death in childhood, but may have
      limitations for health impact evaluation.

PMID- 9009567
TI  - The route of delivery and endothelin-1 levels.

PMID- 9009568
TI  - Effects of albendazole on growth of primary school children and the prevalence
      and intensity of soil-transmitted helminths in Sierra Leone.

PMID- 9009569
TI  - Dysfunction of the blood-cerebrospinal fluid barrier in bacterial meningitis.

PMID- 9009570
TI  - Could we diagnose active schistosomiasis in children by abdominal sonography?

PMID- 9009571
TI  - An approach to evaluate a possible bias in Indian well-to-do standard weight
      values and its implications for interpretations of survey results.
AB  - The results of different Nutrition surveys carried out in India during 1976-1980
      by the National Nutrition Monitoring Bureau (NNMB), Hyderabad, clearly indicated
      that, among preschool age children, girls often fared better compared to boys
      with regard to body weight. In these surveys, Hyderabad well-to-do standards have
      been in use, but it is well documented that, generally, in India girls often have
      higher morbidity and mortality compared to boys. In view of the above, it is
      hypothesized that the values quoted for girls in Hyderabad standard weight values
      are possibly on the low side. A novel approach was developed and the above
      hypothesis was tested with the help of lower percentiles. Analysis suggests that
      there exists a bias and the values quoted for girls in Hyderabad well-to-do
      standard are certainly on the lower side. Hence, as recommended by WHO, there is
      a need to adopt NCHS standard values in assessment of the nutritional status of
      preschool children instead of local standards.

PMID- 9009572
TI  - Suspension model for blood flow through stenotic arteries with a cell-free plasma
      layer.
AB  - The effects of the red cell concentration, the shape of the stenosis and a
      peripheral layer on blood flow characteristics due to the presence of a mild
      stenosis, are investigated. To account for the red cell concentration and the
      peripheral layer, blood is represented by a two-fluid model of particle-fluid
      suspension, and to estimate the effect of the stenosis shape, a suitable geometry
      has been considered such that the axial shape of the stenosis can be changed
      easily just by varying a parameter (referred to as the shape parameter). It is
      shown that the flow resistance increases with the cell concentration but
      decreases with increasing shape parameter. The existence of the peripheral layer
      causes significant reduction in the flow resistance. The wall shear stress
      distribution in the stenotic region and its magnitude at the maximum height of
      the stenosis (i.e., at stenosis throat) possess the variations similar to the
      resistance to flow with respect to any parameter except the shape parameter. The
      latter is independent of the shape whereas the former decreases in the converging
      zone as the shape parameter increases while it increases in the diverging zone in
      a similar situation. To discuss the physiological relevance, the analytical
      results are used to estimate the blood flow characteristics for different
      diseases using the experimental data and the present theoretical approach.

PMID- 9009573
TI  - Analysis of lognormal survival data.
AB  - The failure rate and the mean residual life function (MRLF) of a lognormal
      distribution are known to be nonmonotonic. It is of interest to study the point
      at which the monotonicity changes (the change point). In this article we study
      the change points of the failure rate and the MRLF for the lognormal
      distribution. It is shown that the change points are the solutions of certain
      nonlinear equations. We apply these results to estimate the change points for
      survival data on guinea pigs given by Bjerkedal. The standard deviation of the
      estimate is obtained using bootstrap and jackknife methods. Finally confidence
      bands for the failure rate and the MRLF are also provided to illustrate the
      behavior of the estimates.

PMID- 9009574
TI  - Optimal vaccination strategies for a community of households.
AB  - The effectiveness of a vaccination program depends on how the vaccinations are
      spread over the households of the community. Here we formulate the optimal
      allocation of vaccinations as a linear programming problem, when the objective is
      to prevent epidemics with the minimum vaccination coverage. A vaccine efficacy of
      less than 100%, as is usual in practice, is allowed for. Optimal vaccine
      allocations attempt to leave the same number of susceptibles in every household
      if the disease has a very high transmission rate within households. This means
      that proportionately more individuals need to be vaccinated in larger households
      if the vaccine efficacy is < 100%. The linear programming formulation can
      accommodate heterogeneity among individuals of the proportionate mixing form and
      can also minimize the initial reproduction number for a given achievable
      vaccination coverage.

PMID- 9009575
TI  - Optimal vaccination strategies--for whom?
AB  - A SIRS model with vaccination is considered. The vaccination is assumed to have
      side effects (for simplicity, these side effects are modeled as a probability of
      becoming ill because of vaccination). It is the interest of the total population
      to minimize the prevalence of disease; hence, the vaccination rate that minimizes
      the prevalence will be determined. In Section 2, the individual is considered: an
      individual tries to minimize his or her own risk. This angle of approach results
      in a vaccination rate dependent on the prevalence of the disease. The
      bifurcations of this system are analyzed, and the optimal vaccination coverage
      for the individual is computed. This coverage is then compared with the optimal
      vaccination coverage for the total population: it is found that they disagree for
      some parameter sets.

PMID- 9009576
TI  - Sarcoma: a challenging frontier for the oncologist.

PMID- 9009577
TI  - Biology of sarcomas.

PMID- 9009578
TI  - Soft tissue sarcoma.

PMID- 9009579
TI  - Sarcoma of bone.
AB  - Multiagent chemotherapy and limb salvage surgery are two major advances which
      have occurred over the last twenty years in the treatment of primary bone
      sarcoma. Limb salvage as an alternative to amputation results in improved quality
      of life without a compromise in cure. The complications of limb salvage continue
      to decrease while the durability of the reconstructions continues to improve.
      Chemotherapy has dramatically improved long-term survival, particularly in
      children.

PMID- 9009580
TI  - Head and neck sarcoma.

PMID- 9009581
TI  - The role of radiation in the management of soft tissue sarcoma.

PMID- 9009582
TI  - Chemotherapy for soft tissue sarcomas.

PMID- 9009583
TI  - Health risks among low-income Rhode Island adults.

PMID- 9009584
TI  - Proposed cervical cancer screening recommendations. Rhode Island Department of
      Health Expert Panel on Cancer Screening.

PMID- 9009585
TI  - The invention of the stethoscope.

PMID- 9009586
TI  - Using genetic information: the individual and the community.
AB  - Genetic information is both individual and communal (species and family).
      Responsible use of this information requires exploration of a proper relationship
      between individual and communal values, rights, needs and decision-making. The
      individual/community issue is also important for dealing with the differences of
      emphasis between Western and non-Western cultures in this regard. Non-Western
      cultures emphasize community but also value the individual, while Western
      cultures know extreme individualism is counter-productive. This paper will
      discuss the individual-community relationship as it impacts on various problem
      areas in the utilization of genetic information, e.g. test results which impact
      family as well as individuals and which impact institutional projected costs
      while also making problematic individual access to employment, insurance and
      health care. The paper will also address the pernicious import of the paradigm of
      genetic essentialism which exaggerates individual responsibility while neglecting
      institutional and communal responsibility in genetic matters.

PMID- 9009587
TI  - Illegal drugs policy, AIDS and hepatitis: from prohibition to harm reduction.

PMID- 9009588
TI  - The role of medico-legal reviews in medical research.
AB  - Serial malpractice reviews offer an opportunity for the study of the effects of
      various practice patterns. In the specialty of obstetrics, the usefulness of this
      approach has been demonstrated repeatedly: (a) Much of the data indicating that
      bromocriptine, when given postpartum for milk suppression, has life endangering
      propensities have derived from medico-legal reviews. (b) Important new
      information about factors predisposing to or associated with neonatal brachial
      plexus injuries have emerged from critical analysis of malpractice claims. There
      is reason to anticipate that objective evaluation of the background of other
      prenatal birth injuries can provide more useful clinical information than
      traditional randomized prospective studies.

PMID- 9009589
TI  - Clinical practice guidelines; legal aspects.
AB  - The number of clinical guidelines is rapidly increasing. The proliferation of
      guidelines and their growing use in medical practice make them also more
      conspicuous from a legal point of view. Legal questions relate first of all to
      guideline development: what are the responsibilities of the makers? when are they
      liable for 'defects' in their 'products'? Other questions concern the position of
      doctor and patient: to what extent do guidelines allow for clinical discretion or
      for patient preferences? How are they to be applied by the courts? The paper
      briefly discusses these issues, in particular the question to what extent cost
      benefit considerations may be taken into account in developing clinical
      guidelines.

PMID- 9009590
TI  - Between animal experiments and informed consent.
AB  - Participants in clinical trials, be they healthy human volunteers or patient
      volunteers, are still being exposed to far greater risks than they can imagine.
      Pre-clinical data, on which the clinical trials are based, still rely largely on
      the results of animal experiments, even though the animal tests often have no
      bearing on how man will react to a new drug or a new medical device. The advent
      of genetic engineering, combined with the use of animal-to-human organ
      transplants raises some important scientific as well as ethical questions.

PMID- 9009591
TI  - Trends in American medicine: problems for the defense expert.
AB  - American medicine is undergoing an unprecedented upheaval in its relationship
      with government, third party payers, business and professional groups, with its
      patients, and most of all within itself. These trends take the form of movements
      away from specialization which had been increasing until just recently; the
      introduction of practice criteria and practice guidelines; the virtual
      elimination of fee for service medicine; the creation of multiple physician
      health care organizations working in managed competition; and the grouping of
      doctors into provider organizations offering credit lines to health care systems.
      These trends, along with decreasing reliance on tissue diagnosis, declining
      support of medical research and ever-expanding health care teams have definite
      impact on the issue of negligence. The foregoing is an attempt to define these
      and to make some educated guesses as to their impact on health care delivery in
      the United States in the next several years and the ways in which the negligence
      climate is likely to change.

PMID- 9009592
TI  - No-fault liability--twenty years experience in New Zealand.
AB  - In 1974 the New Zealand Government enacted the Accident Compensation Act to make
      provision for the rehabilitation and compensation of persons who suffer personal
      injury by accident. It abolished actions for damages arising directly or
      indirectly out of personal injury by accident and death resulting therefrom. In
      1992 this Act was replaced by the Accident Rehabilitation and Compensation
      Insurance Act. This paper examines the problems which arose from the
      implementation of the first Act and the reasons for the latest Act.

PMID- 9009593
TI  - Ethics and ethnicity: end-of-life decisions in four ethnic groups of cancer
      patients.
AB  - In the United States, principled based ethics has molded bioethics to a large
      extent. These ethical principles, autonomy, non-maleficence, beneficence,
      veracity and fidelity used in clinical ethics have embedded in them values and
      assumptions. This research examined the end-of-life decisions made by or for
      patients who are Chinese-Americans, Black-Americans, Hispanic-Americans, and
      Anglo-Americans. Patients, their family care-givers and their health care
      professionals were interviewed. These interviews plus observations in the cancer
      clinic raise questions about these principles and asks whether, in an ethnically
      diverse culture, we need to reflect on ethical absolutes and ethical relativism.

PMID- 9009594
TI  - Procreative freedom: a legal and moral challenge.

PMID- 9009595
TI  - Aspects of Mental Health Act 1990 in New South Wales Australia.
AB  - The Mental Health Act 1990 replaced the 1958 Act and brought in many innovations
      which will be discussed. Mental illness is now defined therein but to be mentally
      ill under the Act additional criteria of being a danger to oneself or others has
      to be fulfilled. As a result many patients who are obviously suffering from a
      mental illness but not posing a danger cannot be compulsorily detained in
      hospitals and treated, much to the frustration of doctors, other staff and
      carers. The legislators had the view that a person has the right to go silently
      mad. Obviously such patients will not admit themselves voluntarily as Informal
      patients. Were it not for a certain vocal consumer group (Manic Depressive Self
      Help Group) who strongly lobbied the politicians to force changes to the Act (to
      specify that a person suffering from a severe disturbance of mood and who arising
      out of such disturbed mood could bring on serious financial harm or serious
      damage to his/her reputation could also be detained and treated) a significant
      number of maniacs (who weren't posing a serious risk of harm to themselves or
      others) would have gone untreated with disastrous consequences. The new Act
      creates a new category of Mentally Disordered Person (no matter what the
      underlying stresses/precipitants may be a person who poses a temporary serious
      risk of harm to himself or others) where such person can be admitted and treated
      for up to 3 working days. All mentally ill or mentally disordered persons have to
      have certification from at least one psychiatrist and one other doctor. The
      mentally ill persons have to be finally seen by a magistrate at a hearing at the
      hospital and the magistrate can either order adjournment, detention for up to
      maximum of 3 months or discharge. Appeal provisions to Mental Health Tribunal and
      Supreme Court exist. The Act also contains guidelines for the use of E.C.T. and
      medication. Whilst a useful piece of legislation, obviously it is not without
      problems. It sets out to protect (with measurable success) the rights of the
      mentally ill but some of its restrictive provisions deny many mentally ill
      persons a basic right (the right to prompt and early treatment) and cause great
      anguish to affected families and mental health professionals.

PMID- 9009596
TI  - Protecting the rights of detained patients.
AB  - Compulsory detention in a psychiatric hospital constrains, but does not remove
      the rights of those admitted. The mental health laws of different countries
      provide for various mechanisms intended to protect the rights of detained
      patients. In the U.K. the Mental Health Act Commission (MHAC) was established to
      oversee the implementation of the 1983 Mental Health Act as a whole, and to
      ensure the proper treatment of individuals detained under the Act. This paper
      will consider the way in which the MHAC fulfills its remit, and reflect on its
      capacity to preserve the rights of mentally disordered people as citizens as well
      as patients.

PMID- 9009597
TI  - Death by inmate--multiple murder in a maximum security prison.
AB  - The authors report the killing of two inmates by a third inmate in a maximum
      security prison in the State of Wisconsin. All three had been sentenced to life
      imprisonment for murder, and one as a notorious serial killer. They touch on the
      variables of jail/prison overcrowding, the psycho-social traits and
      psychopathology of inmates, and their ethnicity as potential factors in violent
      crimes. They conclude that the selection of inmate housing should take into
      consideration the past history, the personality and the possible psychopathology
      of the inmate.

PMID- 9009598
TI  - Advances in domestic violence shelters.
AB  - Domestic violence can be found in every local, region, and nation. Domestic
      violence permeates every segment of society, including those from lower socio
      economic groups, and those from higher socio-economic groups. Domestic violence
      can be found in various religious, ethnic backgrounds, and cultures as well as in
      ancient and modern society. It is only recently that society in general has
      started to address the problems of domestic violence and deal with them in
      concrete ways. This presentation will show how "WINGS", Women In Need Growing
      Stronger, has set up and utilized a series of homes, and apartments that offer
      various levels of support and structure rather than the traditional large
      facility and how they encouraged women to regain self confidence and integration
      back into society.

PMID- 9009599
TI  - Ethical and legal issue raised by DNA fingerprinting in France.
AB  - As soon as DNA identification tests have been introduced as a new powerful tool
      in criminalistics and in paternity testing, this new technology has immediately
      aroused a mixture of ethical concerns, suspicion and interest among scientists
      and non-scientists. The major concerns about the so called 'DNA fingerprints'
      were related first to the possible constitution of data based by the police
      agencies for the purpose of identifying and investigating individuals as
      potential criminal suspects, and secondly to the risk of a widespread use without
      safeguards for private investigation as establishing paternity or the typing of a
      person for insurance companies. In this context, and in order to preserve civil
      liberties and the respect of individual privacy, the national Consultative
      Bioethics Committee advised, as early as 1989, the French government that DNA
      identification should be strictly limited to judicial use and performed by
      accredited laboratories. After a long debate, this recommendation has finally
      been adopted in July, 1994 by the French Parliament. As a result, France is
      presently the only member state of the European Union with such restricted
      legislation. This is not without raising difficulties in the implementation of
      the law, especially in the field of paternity testing where the demand is growing
      and can be satisfied in any other neighbour country.

PMID- 9009600
TI  - Alcohol intoxication and homicide.

PMID- 9009601
TI  - Informed consent: research and the psychotic patient.
AB  - During the past few decades, western societies seem to have placed a particularly
      high premium on the individual's personal integrity and right to self
      determination. Presently, obtaining a patient's consent is accepted as a
      prerequisite for the performance of any form of medical treatment, whether
      diagnostic or therapeutic in nature. A study was undertaken in various centres
      involved with clinical trials to compare the procedures used for obtaining
      informed consent from a psychotic patient. Although the study did not investigate
      the legal aspects related to consent and informed consent, it is necessary that
      one must be aware of these aspects when doing clinical trials.

PMID- 9009602
TI  - Medical records and access thereto.
AB  - Medical records are essential tools in the practice of medicine. They are
      important in the planning and monitoring of patient care and for the protection
      of the legal interests of patients, hospitals and doctors. There is a legal duty
      on doctors to maintain confidentiality and failure to do so may result in an
      action for invasion of privacy, defamation or even breach of contract. There are,
      however, exceptions to this rule. There are procedural remedies available to
      obtain access to medical records where they are relevant to civil or criminal
      proceedings. There are also constitutional provisions under the Interim and
      Working Draft Constitutions which may allow such access. The former only applies
      to records held by the state while the latter applies to both state and privately
      held records. Ownership of medical records usually vests in the doctor or
      institution treating the patient, but such ownership is custodial rather than
      absolute. Patient records should be accurate, objective and contemporaneous. The
      international trend is to allow patients to inspect their records and to allow
      them to make copies thereof. It is submitted that given the provisions of the
      Interim and Working Draft Constitutions the same should apply in South Africa.

PMID- 9009603
TI  - Unwanted pregnancy: it's existing solutions from the perspective of young adults
      in Bangkok and the Abortion Law.
AB  - 727 students of 15 to 24 years old in Bangkok were randomly selected to study
      their opinion towards existing solutions for unwanted pregnancy and the
      conformity or controversy of their suggested solutions to Thai Abortion Law. The
      SPSS/PC package program was used for data analysis. The results show that more
      than 80 percent of the youth in this study do not prefer the abortion method,
      despite it's being vastly used as a mean of solving the problem and that the
      abortion must be done under the Thai Criminal Law section 305 (1) and (2).
      Otherwise, it might be reasonable for some critical medical conditions such as
      high risk pregnancy or anti HIV+ve. Hence, it is confirmed that the youth opinion
      towards abortion agree with the law almost completely except for the aspects of
      the baby's health and genetic diseases. With regard to better solutions of
      unwanted pregnancy, Thai young adults strongly recommend resolutions of allowing
      progress of pregnancy on the basis of kindliness and understanding of human-being
      in crisis with warm support from within and outside the families. Besides,
      strengthening of virtue of Thai culture along with sufficient sex education for
      young generation are also needed.

PMID- 9009604
TI  - Euthanasia: reconciling culture and human rights.
AB  - The constitutional justifiability of euthanasia will depend upon interpretation
      of the right to life and the right to respect for and protection of one's
      dignity. Pertinent issues arising hereto are: In our new value-based
      constitutional interpretation, what are the values underlying our multi-cultural
      society? Issues of death and dying are inter-linked to a civilization's world
      view and its approach to human dignity. Western, African and Islamic approaches
      will be compared. Does euthanasia negate the essential content of the right to
      life and is its limitation on such right reasonable/justifiable in an open and
      democratic society based on freedom and equality.

PMID- 9009605
TI  - Euthanasia in relation to newborn babies--a comparative study of the legal and
      ethical issues (II).

PMID- 9009606
TI  - Restraining patients as part of hospital policy.
AB  - In Israel, senior citizens spend more time in hospitals than do members of any
      other age group. Chronic, age-related illnesses make the senior population
      especially dependent on the hospital system. Hospitalization, however, has its
      own risks-frequent and/or prolonged hospital stay can increase susceptibility to
      infections and complications, and can lead to impairment of mobility and of
      overall functioning. In this study, we'll be taking a look at the use of patient
      restraints in geriatric institutions. We'll look at the factors that induce
      attending staff to restrain elderly patients, the kinds of restraints used, and
      the feeling of the staff on this controversial issue. We'll also present the
      results of interviews with nursing services administrators in several geriatric
      institutions on the subject of restraining policies and procedures. Our findings
      indicate that procedures and policies regarding restraint vary from one
      institution to another. In some cases there are no clear written procedures, and
      patients are restrained without the written and signed order of a physician. We
      also found that attending staff are not sufficiently knowledgeable about the
      legal issues involved in patient restraint.

PMID- 9009607
TI  - Diagnosing environmental disasters.

PMID- 9009608
TI  - Tips for improving the MMA's home page.

PMID- 9009609
TI  - Unraveling the mysteries of environmental medicine.

PMID- 9009610
TI  - Rescue worker and population protection in large-scale contamination disasters.
AB  - We discuss disaster preparedness and emergency response to large-scale disasters.
      Our particular focus is disaster management and protection of disaster response
      personnel in situations involving chemicals and radiation. We describe a unit
      system that protects rescuers working in the epicenter of a disaster, and we
      examine effective protective clothing and procedures for enhancing human
      performance in extreme environmental conditions. We also present on outline of
      patient triage in response to radiation disasters. Finally, we describe recent
      efforts underway in Minnesota to prepare for managing large-scale disasters.

PMID- 9009611
TI  - Conducting truck drivers' physical exams. The high prevalence of sleep apnea.

PMID- 9009612
TI  - Do state licensing procedures discriminate against physicians using mental health
      services? One physician calls for reform.

PMID- 9009613
TI  - Protecting physicians and the public interest.

PMID- 9009614
TI  - The impact of the Americans with Disabilities Act on medical licensing and
      credentialing.

PMID- 9009615
TI  - "Kids caught in the middle".

PMID- 9009616
TI  - The hook that kills ... Missouri's children are being hooked on cigarettes at a
      much younger age.

PMID- 9009617
TI  - An income-based approach for evaluating the financial components of capitated
      managed care contracts.
AB  - In this fictitious example the contractual reimbursement level being reviewed
      would produce an annual income level of $246,564, if we could replace 100% of our
      practice with patients at this reimbursement level. This resulted in a 64%
      increase over the income level shown in the example. In this example we have
      learned that this is a very favorable contract and we should identify and employ
      techniques to increase the volume from this payer. If, on the other hand, this
      analysis had shown that the capitation rates reduced the current income level we
      should implement measures to limit the extent of volume that this contract
      represents in the practice. If you desire the actual increase or decrease in
      income expected from the volume associated with this contractual arrangement can
      be calculated. To do this one needs to estimate the number of members in the plan
      that will choose to be in your panel and then calculate the volume and
      reimbursement level associated with this patient population. Rarely, does this
      next level of calculation need to be performed. It is usually quite clear, from a
      decision-making and negotiating perspective prior to going to this level of
      detail, if the contract in question is attractive or not attractive.

PMID- 9009619
TI  - Managed care reform in the political limelight.

PMID- 9009618
TI  - Supervising RNs and advance nurse practitioners: new regulations for Missouri.

PMID- 9009620
TI  - Joint interim committee on managed care. Recommendations to the General Assembly.

PMID- 9009621
TI  - Respiratory medicine and Europe.

PMID- 9009622
TI  - Spinal tuberculosis: a report of five cases and a review.
AB  - Spinal tuberculosis (TB) is an uncommon occurrence in developed countries. We
      present five cases of spinal TB illustrating some of the problems that can be
      encountered in clinical practice. Delay in diagnosis due to physicians
      unawareness of TB as a diagnostic possibility in patients with persistent back
      pain was observed in two patients. A high clinical index of suspicion is,
      therefore, needed for diagnosis. Tuberculin skin testing was positive in four
      patients. Computed tomography (CT) has become the examination of choice. It
      allows precise location of lesions and their extension to paraspinal soft tissue.
      Furthermore, abscess aspiration and biopsy specimens can be obtained under CT
      guidance. Magnetic resonance imaging in patients with neurological involvement
      may provide better information than CT. Definitive diagnosis depending on
      histological examination, smear and culture of biopsy material, however, may be
      difficult to obtain. In three patients, diagnosis was based on clinical
      presentation and response to therapy. Antituberculosis chemotherapy was highly
      effective in curing all patients. Management of patients should be ensured by
      experts in antituberculosis chemotherapy, usually chest physicians.

PMID- 9009623
TI  - Pulmonary actinomycosis: surgical considerations.
AB  - Pulmonary actinomycosis is a rare disease. Of 2,247 patients presenting with a
      radiological pulmonary opacity, 13 (0.6%) were identified with pulmonary
      actinomycosis in a 13 year period. Twelve of the 13 patients underwent
      thoracotomy and one had clinical diagnosis and subsequent medical treatment
      alone. Neither mortality nor major complications were observed. One patient had
      recurrent disease after surgery. The other surgical patients are well and free
      from disease at a minimum 6 month follow-up. Diagnosis of actinomycosis is
      frequently difficult because it often infects pre-existing cavitary disease in
      the lung. As a consequence, the infection may progress to stages which will not
      respond to medical treatment alone. Surgery then provides the best method to
      achieve diagnosis and ultimate treatment.

PMID- 9009624
TI  - Determinants of chronic bronchitis prevalence in an elderly sample from south
      west of France.
AB  - This paper attempts to estimate by means of a cross-sectional study in subjects
      aged 65 yrs and over the determinants of the prevalence of chronic bronchitis
      according to age, gender, smoking history, educational level, former occupation
      and associated morbidity. Data were examined from the third year of a cohort
      (Personnes agees QUID (PAQUID)) and concerned 2,406 subjects. Identification of
      chronic bronchitis was based on a direct question asking for the presence of
      phlegm on most days during at least 3 months per year for at least the two
      previous years. Of the sample, 13% reported chronic bronchitis (20% of males, and
      8% of females). A multivariate analysis was performed and showed that chronic
      bronchitis was linked to sex, smoking history and professional category.
      Independent of these factors, asthma history and digitalic drug therapy were also
      closely associated to chronic bronchitis. These results underline the long-term
      effect of smoking and occupation on chronic bronchitis, and also illustrate the
      strong association with asthma and cardiac morbidity over 65 yrs of age.

PMID- 9009625
TI  - Plasma hormone levels and haemodynamics in patients with chronic obstructive lung
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with right heart
      failure and salt and water retention. The possible roles of haemodynamically
      active hormones in the early stages of COPD have not previously been described.
      Adrenaline, noradrenaline, renin activity, aldosterone, vasopressin, cortisol,
      growth hormone, prolactin and atrial natriuretic peptide (ANP) were measured
      during right heart catheterization in mixed venous blood and in a peripheral
      artery, in the supine and standing position, in two groups of patients with COPD:
      Group A with arterial oxygen tension (Pa,O2) < 8.0 kPa (60 mmHg) and Group B with
      Pa,O2 > 8.0 kPa (60 mmHg). A group of 15 control subjects was studied to obtain
      control hormonal measurements with a venous blood sample only. Haemodynamic and
      blood gas values and hormone levels were measured in the supine and standing
      positions to record changes in the various parameters in COPD patients, and the
      relationship between pulmonary haemodynamics and hormone levels. No differences
      were found in hormonal samples between peripheral artery and mixed venous blood.
      In comparison with the control group, both groups of COPD patients showed a
      significant reduction in cortisol (p < 0.0001) and in vasopressin (p < 0.005),
      and an increase in ANP (p < 0.05) and growth hormone (p < 0.05). A marked, but
      not significant, increase in renin activity, and aldosterone was also found.
      After standing the increment of adrenaline was significantly higher in COPD
      patients (p < 0.02). A significant inverse relationship was recorded between
      forced expiratory volume in one second (FEV1) and noradrenaline (p < 0.02). There
      is a complex hormonal response even in the early phase of chronic obstructive
      pulmonary disease. An increase of plasma levels of atrial natriuretic peptide
      appears to be the earliest neuroendocrine response in these patients.

PMID- 9009626
TI  - Mixed infection by Staphylococcus and Candida, and Wegener's granulomatosis.
AB  - We describe the case of a patient who initially presented with pneumonia from
      Staphylococcus aureus and Candida parapsilosis, which was resolved with
      antibiotic treatment, but reappeared 6 months later as full-blown Wegener's
      granulomatosis. The possible pathogenetic correlations between infective agents,
      in particular Staphylococcus aureus and Candida, and Wegener's granulomatosis are
      discussed.

PMID- 9009627
TI  - Rapid healing of endobronchial tuberculosis by local endoscopic injection of
      corticosteroids.
AB  - We report a case in which two endobronchial tuberculous lesions were diagnosed by
      bronchoscopy. Under antituberculosis chemotherapy, one lesion was submucosally
      injected with corticosteroids. Twelve days later, this lesion had almost
      completely disappeared, whereas the other lesion had remained unchanged. The
      latter lesion was then injected with corticosteroids, which resulted, 14 days
      later, in complete healing. Six months later, there were no stenotic or other
      lesions. These observations suggest that local injection of corticosteroids in
      endobronchial tuberculous lesions induces a rapid and complete resolution of
      these lesions, and may prevent the development of bronchostenosis.

PMID- 9009628
TI  - New antimycobacterial agents.
AB  - The resurgence of tuberculosis and the increased prevalence of atypical
      mycobacterial infections in immunocompromised subjects have prompted the quest
      for novel antimycobacterial agents. Fluoroquinolones, such as ofloxacin and
      ciprofloxacin, might be promising agents for treatment of tuberculosis especially
      multidrug-resistant tuberculosis (MDR-TB) and infections caused by Mycobacterium
      fortuitum. Clarithromycin, an important member of the macrolides, has been shown
      to have activity against some infections due to Mycobacterium avium
      intracellulare, M. fortuitum and Mycobacterium chelonae. Rifabutin, being a
      rifamycin, has been found to be efficacious in treatment of drug-susceptible
      tuberculosis, although its place in MDR-TB is less certain. Rifabutin in
      combination with other drugs might constitute active regimens for treatment of
      disseminated M. avium-intracellulare infections. When used alone, it can be an
      active prophylactic agent against such infection. Imipenem, a carbapenem, might
      provide promising treatment for some M. fortuitum and M. chelonae infections. The
      place of beta-lactam-beta-lactamase inhibitor combinations in the treatment of
      MDR-TB is uncertain. Clofazimine and aminosidine being riminophenazine and
      aminoglycoside, respectively, might merit further evaluation as potentially
      useful agents for treatment of MDR-TB and M. avium-intracellulare infections.
      However, much broader evaluation of all these agents in clinical settings is
      still definitely required.

PMID- 9009629
TI  - Drugs by inhalatory route: an overview and upcoming clinical perspectives.
AB  - The physical properties of aerosols are reviewed. The physiological basis of
      inhalation therapy is then briefly reviewed together with the aerosol devices
      currently available and the therapeutic uses of inhaled drugs, focusing on the
      treatment of parenchymal lung diseases and extra respiratory disorders. Finally,
      new perspectives for inhalation therapy are examined.

PMID- 9009630
TI  - Maturational aspects of human airway smooth muscle function.
AB  - Maturational changes in the contractility and sensitivity of airway smooth muscle
      have been studied in an attempt to explain the increased incidence of asthma in
      children compared with adults. These changes are not uniform between species,
      however, and a clear relationship between in vitro muscle function and clinical
      disease does not yet exist. Over the last several years, investigators have used
      bronchoconstrictor challenge tests to assess airway reactivity in infants, with
      pulmonary functions reflecting drug effects. These tests represent changes in
      airway calibre, which may or may not result from differences in muscle
      sensitivity or contractility. Instead, the forces which oppose smooth muscle
      shortening, and which themselves undergo maturational change, may be responsible
      for the perceived heightened airway responsiveness of infants and young children.
      This paper reviews current knowledge regarding maturational changes in the
      properties of airway smooth muscle, and in the physiological forces which oppose
      smooth muscle shortening and airway narrowing.

PMID- 9009631
TI  - Problems with the retrieval of long-standing inhaled foreign bodies in children.
AB  - In the last 7 yrs, we have removed 51 foreign bodies inhaled by children. In five
      cases involving long-standing foreign bodies, retrieval of the inhaled objects
      was complicated by their peripheral location in the bronchial tree and by the
      presence of abundant granulation tissue. In two of these children, the inhaled
      foreign bodies had been pushed further down the bronchial tree during a previous
      unsuccessful bronchoscopy. The use of a rigid bronchoscope with optical peanut
      forceps and 2-4 doses of an aqueous solution of epinephrine 1:100,000, at the
      dosage of 0.1 mL.kg-1.body weight (during removal of granulation tissue and after
      removal of the foreign bodies) permitted the complete removal of the foreign
      bodies in one session and a good control of bleeding.

PMID- 9009632
TI  - Early bronchopleural fistula after lung resection.
AB  - Bronchopleural fistula (BPF) is a dramatic complication after lung resection. Its
      incidence ranges 1-4% and most cases occur after right pneumonectomy. A careful
      surgical technique of bronchial closure is necessary to avoid this complication.
      Occult bronchopleural fistulas can be treated conservatively, unless there are
      signs of infection. Immediate drainage of the postpneumonectomy space is
      mandatory for a bronchopleural fistula which becomes clinically evident. Very
      small fistulas can be closed by the application of fibrin glue. For an early
      postpneumonectomy fistula, reoperation is necessary, with redivision and suturing
      of the bronchial stump. The bronchial suture line should be covered by omentum,
      pericardial fat or a muscle flap to provide viable tissue. Even with current
      techniques, morbidity and mortality of this serious complication remain high.

PMID- 9009633
TI  - Multiple functions of alpha 1-antitrypsin and alpha 1-antichymotrypsin. 1. Role
      of lung epithelial cells in the proteinase-proteinase inhibitor balance.

PMID- 9009634
TI  - Home mechanical ventilation in children: techniques, outcomes and ethics.
AB  - Various neuromuscular and pulmonary disorders can cause ventilatory failure in
      children. Tracheostomy ventilation in the home is especially valuable in younger
      children who require ventilatory support for most of the day and who have bulbar
      dysfunction but newer noninvasive techniques especially nasal mask ventilation
      are often preferable. It is important to select the type of ventilator and to
      choose the interface with the patient carefully in order to maximise the child's
      quality of life.

PMID- 9009635
TI  - Comparison of methods of measuring static lung volumes.
AB  - The measurement of static lung volumes is important for the accurate diagnosis of
      lung disorders, and when making volume-dependent measurements, such as airways
      resistance. There are a variety of methods available. The most accurate method is
      that of constant volume body plethysmography, which provides an estimate of total
      lung capacity regardless of the presence of airflow obstruction. Whilst this
      method may overestimate lung volumes in asthmatics, and is technically more
      demanding than gas dilution methods, this should be regarded as the principal
      method for estimating lung volumes. Gas dilution estimates of multi-breath helium
      or nitrogen dilution or single-breath estimates using the same gases all
      underestimate total lung capacity in the presence of airflow obstruction. Single
      breath methods will underestimate volumes to a greater extent than multi-breath
      methods. Multi-breath helium dilution is currently regarded as the acceptable
      alternative to body plethysmography. Estimates of lung volumes from chest
      radiographs provide an estimate of lung volumes independent of airflow
      obstruction. They are probably prone to greater variability than body
      plethysmographic estimates, and it is regarded as unacceptable to expose patients
      to excess radiation. Other methods being developed include estimates from nuclear
      magnetic imaging and computed tomography.

PMID- 9009636
TI  - Home oxygen therapy: a global view.

PMID- 9009637
TI  - Long-term oxygen therapy in The Netherlands.

PMID- 9009638
TI  - Home oxygen therapy in Australia.

PMID- 9009639
TI  - Respiratory home care in Poland.

PMID- 9009640
TI  - The place of exercise reconditioning in the rehabilitation of COPD patients.

PMID- 9009641
TI  - Antifungal prophylaxis with itraconazole in neutropenic patients:
      pharmacological, microbiological and clinical aspects.

PMID- 9009642
TI  - Fluconazole in the prophylaxis of fungal infection after bone marrow
      transplantation.
AB  - An open, non-comparative study was conducted to investigate the efficacy and
      safety of fluconazole in the prophylaxis of superficial or systemic fungal
      infections in patients having received bone marrow transplantation (BMT). The
      study population consisted of a total of 53 patients, including 10 children
      between the ages of 3 and 14 years who were scheduled for BMT. Fluconazole
      prophylaxis was initiated at 200 mg day-1 in adults and 100 mg day-1 in children.
      It was started at a mean of 7 days before treatment and continued for up to 112
      days in the paediatric patients and 393 days in the adult patients. Apart from
      the baseline examination and the final evaluation, the patients were evaluated
      mycologically and serologically for the presence of fungal infections on a weekly
      basis, if feasible. Proven fungal infection, oesophageal candidosis or
      oropharyngeal candidosis was not found in any of the patients under study during
      the fluconazole prophylaxis. Thirteen of the adult patients developed unexplained
      fevers and had their treatment supplemented by antibiotic therapy and treatment
      with amphotericin B. In all 10 children, the prophylactic treatment proved
      successful. Adverse events were seen in 15 patients. In one case only, the event
      was judged to be causally related or possibly causally related to the study drug.
      Hence, fluconazole proves to be an effective and well-tolerated agent in the
      prophylaxis of fungal infections in recipients of bone marrow transplants.

PMID- 9009643
TI  - Microsporum canis infections in children: results of a new oral antifungal
      therapy.
AB  - Clinical and laboratory data from 22 children with tinea corporis and tinea
      capitis caused by Microsporum canis (10 tinea corporis, 12 tinea capitis),
      confirmed by microscopic examination and culture and partly pretreated with
      griseofulvin or terbinafine, are summarized. The children were treated
      consecutively with itraconazole in our clinic during 1994/95. The age of the
      children ranged between 4 and 13 years, with girls being affected much more
      frequently than boys. Oral, individually adapted, high-dose treatment of 5 mg
      itraconazole per kg body weight proved to be successful. In all 22 children,
      although pretreatment with griseofulvin or terbinafine was partly unsuccessful,
      fungal infections could be cured clinically and also were culture negative at
      control examinations. In 10 children with tinea corporis treatment was performed
      only for 4-14 (middle 11) days. In the children with tinea capitis itraconazole
      treatment was continued for 3-11 weeks. Among the six children without
      pretreatment, itraconazole solution was administered for 4-11 weeks (average 7.5
      weeks). Of the patients in whom pretreatment was unsuccessful, four with
      griseofulvin and two with terbinafine, the duration of the subsequent oral
      treatment with itraconazole solution was 3-5 weeks (average 3.6 weeks). The drug
      seemed to be well tolerated-no significant side-effects occurred, with the
      exception of possible minor gastrointestinal disturbances in two patients.
      Laboratory values remained within normal limits.

PMID- 9009644
TI  - The morphology of Candida albicans in two different Earle base media in the
      presence of tunicamycin.
AB  - The effect of tunicamycin on the morphology of Candida albicans yeast cells and
      germ tubes grown in two different Earle's minimal essential media was
      investigated. Tunicamycin inhibited germ tube and mycelia formation. Inhibition
      increased the size and caused aberrant morphology of yeast cells, including bud
      formation. These cells are hydrophobic and could be used for the production of
      two monoclonal antibodies suitable for the study of adhesion phenomena as well as
      ectomural properties.

PMID- 9009645
TI  - Partial characterization of proteolytic enzymes of Microsporum canis and
      Microsporum cookei.
AB  - Characterization by proteinase inhibitors of the enzymes produced by Microsporum
      spp. revealed that Microsporum canis and Microsporum cookei produce serine
      proteinase(s), but only M. canis expresses aspartic and cysteine proteinases and
      probably a metalloproteinase. Both M. canis and M. cookei expressed
      metalloelastinolytic proteinases. All the proteinase types have been implicated
      in the pathogenicity of a wide range of microorganisms.

PMID- 9009646
TI  - Long-term observation of a case of cutaneous blastomycosis in Poland treated with
      fluconazole.
AB  - The case of a 63-year-old carpenter with cutaneous blastomycosis is presented.
      The patient contracted the disease in 1974 when his leg was injured by a piece of
      rotten wood during repair works in deep cellars in Lublin's Old Town. Six months
      later a nodular lesion extending peripherally with hyperkeratosis developed at
      the site of the injury. The lesions slowly spread to cover more than half of the
      skin surface of the body. Some of them had regressed spontaneously, leaving
      cicatrization. Initially, anti-inflammatory treatment was given. Ten years later,
      in 1984, antimycotic therapy with various antifungal agents was instituted.
      Improvement appeared to be greatest with fluconazole treatment.

PMID- 9009647
TI  - Geotrichosis of oral mucosa.
AB  - A livid, sharply defined enanthema of the oral mucosa with ulcerations on the
      soft palate in a patient presenting with de novo acute myeloid leukaemia with
      prolonged, therapy-induced granulocytopenia (< 0.5 nl-1 for 113 days!) was
      diagnosed as geotrichosis. Geotrichum capitatum was identified both in vivo and
      in vitro. Pneumonic infiltrates in the upper lobes of both lungs were treated
      with amphotericin B infusions. Healing of the aforementioned enanthema was only
      achieved after addition of 5-fluorocytosine to therapy. Susceptibility
      determinations with several Geotrichum capitatum isolates led to the conclusion
      that amphotericin B was unsuitable as a therapeutic agent in this case. 5
      Fluorocytosine and itraconazole exhibited superior antifungal and antimycotic
      activity.

PMID- 9009648
TI  - The spectrum of dermatophytes in northern Malawi (Africa).
AB  - Between 1.5% and 2.5% of the population in Karonga District, northern Malawi
      (Africa), were diagnosed as having tinea faciei, corporis, inguinalis or cruris
      in the course of a total population survey carried out between 1987 and 1989.
      With regard to the relative frequency distribution of dermatophytes, the main
      findings were the rarity of Trichophyton rubrum (around 1%) and the predominance
      of Microsporum audouinii (57%) in this part of Africa. In the genital area
      Epidermophyton floccosum was the most common isolate (56%).

PMID- 9009649
TI  - Tinea capitis in adults.
AB  - Between 1973 and 1994, 17 cases of tinea capitis in adults were observed in the
      Dermatology Clinic of the University of Cagliari (Italy). The patients were all
      women (age range 17-76 years) and came from the district of Cagliari. At the time
      of referral, they presented with a disease duration varying from 8 to 10 months.
      The main clinical feature was scalp lesions, but in two cases mycotic lesions on
      the face were also present. The following dermatophytes were isolated:
      Microsporum canis (eight cases), Trichophyton violaceum (four cases),
      Trichophyton mentagrophytes (four cases) and Trichophyton verrucosum (one case).
      Systemic treatment with griseofulvin or terbinafine led to complete recovery in
      40-50 days. In discussing the pathogenesis and transmission mode of the disease,
      the authors hypothesize that endocrine disorders influencing the secretion and
      composition of sebum may facilitate dermatophyte invasion of the scalp in the
      adults.

PMID- 9009650
TI  - Dermatophytosis in schoolchildren in Ekpoma, Nigeria.
AB  - Of 1400 pupils from two public primary schools in Ekpoma, Edo State, Nigeria, who
      were screened for dermatophyte infection, 188 (13.4%) were infected. The
      causative agents isolated included Microsporum audouinii in 88 (46.8%),
      Trichophyton mentagrophytes in 48 (25.5%), T. rubrum in 40 (21.3%), T. tonsurans
      in four (2.1%) and Epidermophyton floccosum in eight (4.3%). There were
      significant differences in the rate of infection between male and female
      schoolchildren as well as between children from different socioeconomic
      backgrounds.

PMID- 9009651
TI  - Psoriasiform id reaction in tinea corporis.
AB  - A case of tinea corporis due to Microsporum canis followed by a scattered
      psoriasiform eruption is reported. The nature, clinical features and pathogenesis
      of the dermatophytid are discussed.

PMID- 9009652
TI  - In vitro susceptibility of Malassezia furfur against azole compounds.
AB  - The minimum inhibitory concentrations (MICs) for 30 isolates of Malassezia furfur
      of four azole compounds-bifonazole, climbazole, clotrimazole and ketoconazole
      were determined as these substances are used in the topical therapy of M. furfur
      associated skin conditions. M. furfur is a lipophilic fungus with complex growth
      requirements; the MICs were measured in a microdilution test system in modified
      Leeming-Notman medium by a colorimetric read-out with alamarBlue. The MICs of
      bifonazole ranged between < 0.06 and 1 microgram ml-1 with an empirical median of
      0.06 microgram ml-1 for climbazole the MICs were < 0.06 to 0.5 microgram ml-1
      (median < 0.06 microgram ml-1), for clotrimazole < 0.06 to 8 micrograms ml-1
      (median 1 microgram ml-1), and for ketoconazole < 0.06 to 0.12 microgram ml-1
      (median < 0.06 microgram ml-1). Climbazole and ketoconazole showed similar in
      vitro activity against M. furfur, with bifonazole having slightly lower, and
      clotrimazole the lowest in vitro activity. These findings may be explained by the
      extremely low water solubility of the last two compounds; the results have yet to
      be correlated with the in vivo efficacy of these substances.

PMID- 9009653
TI  - Characteristics of Malassezia pachydermatis strains isolated from canine otitis
      externa.
AB  - The morphological, cultural and biochemical characteristics of 80 M.
      pachydermatis strains isolated from cases of canine otitis externa were studied.
      Microscopically, the strains could be subdivided into two phenotypes. All M.
      pachydermatis strains grew well on Sabouraud glucose, yeast morphology and
      modified malt extract agar, but formed two distinct colony types. All strains
      were characterized by no fermentation. Assimilation of glucose, mannitol (42
      strains), sorbitol (40 strains) and peptone was observed, but no ethanol
      assimilation. Urease and catalase tests were positive, while indole and acetoin
      production was not detected. All strains showed proteinase, caseinase,
      lecithinase and peroxidase positivity but to varying extents. Esterase activity
      was observed for all Malassezia strains when using Tween 20, 40 and 60, whereas
      Tween 80 was hydrolysed by only 42 strains. No coagulase or haemagglutinating
      activities were detected. When compared for satellite phenomenon and vitamin
      requirements, some Malassezia strains could not grow in the absence of nicotinic
      acid but grew well in the presence of staphylococci. In susceptibility tests, all
      strains showed the highest susceptibility to ketoconazole. On the basis of the
      biochemical differences, M. pachydermatis seems to be a heterogeneous species and
      can be divided into two groups.

PMID- 9009654
TI  - Clinical use of oral nystatin in the prevention of systemic candidosis in
      patients at particular risk.
AB  - Systemic candidosis is currently a major concern among certain groups of patients
      at particular risk because of recent treatment modalities. To prevent spread of
      Candida albicans, in particular, from the orogastrointestinal tract antimycotic
      treatment would appear beneficial. So far, however, suitable drugs are rare.
      Polyenes, and in particular oral nystatin, are the main ones considered so far.
      More recently, the oral azoles have provided therapeutic alternatives. In this
      review the current role of nystatin and, in particular nystatin tablets, which
      are better accepted than suspensions at higher dose levels, is described,
      focusing on efficacy and safety as determined in controlled trials. Recent
      evidence suggests that oral application of nystatin tablets can be considered
      both efficacious and safe in the appropriate context. The relative potency of
      oral nystatin and systemic azoles, particularly ketoconazole and fluconazole,
      awaits final determination.

PMID- 9009655
TI  - Detection of Candida albicans DNA with a yeast-specific primer system by
      polymerase chain reaction.
AB  - The in vitro and in vivo selectivity and sensitivity of a yeast-specific primer
      system was investigated. A two-step polymerase chain reaction (PCR) was used: the
      first amplified a 245-bp fragment of the gene for cytochrome P450L1A1 and the
      second a product of 193 bp. This nested PCR produced an approximately 1000-fold
      increase in the sensitivity of the test for Candida albicans DNA compared with
      the first primer pair. The lower level of sensitivity of the test in
      physiological saline and tissue homogenate was about 10 C. albicans cells ml-1.
      On the other hand, the sensitivity of the nested PCR method was reduced by a
      factor of more than 1000 when C. albicans was fixed with 4% formalin. After i.v.
      injection of different doses of C. albicans into mice, the yeast could be
      demonstrated in blood and in six different organs. The nested PCR was to some
      extent more sensitive than culturing for the detection of the yeast in the
      specimens of organs such as lung, cardiac muscle, liver, kidneys and brain. In
      contrast, in blood and spleen the culture was superior to the PCR technique used.
      Nested PCR is thus a useful additional method for the demonstration of yeasts.

PMID- 9009656
TI  - Fluorometric determination of acid proteinase activity in vulvovaginal
      candidosis.
AB  - Vulvovaginal candidosis is one of the most frequent disorders in obstetrics and
      gynaecology. Candida albicans is commonly considered to be the true vaginopathic
      agent. The secreted acid proteinase might be especially relevant in the
      pathogenesis of vulvovaginal candidosis. A fluorometric determination of acid
      proteinase activity of clinical C. albicans isolates was carried out during the
      present work using fluorescamine. L-Leucyl-L-alanine was included as an internal
      standard and the results were expressed as nmoles of leucylalanine equivalents h
      1 per 2 x 10(4) cells. The 13 isolates were taken from non-diabetic, non-pregnant
      women aged 22-35 years with vulvovaginal candidosis. Candida albicans ATCC 44858
      was used as a control. The proteinase activity in culture supernatants was
      detectable starting from the mid- to late- exponential phase of growth, peaked
      between 30 and 46 h, and then declined. The control had an activity of 2.72 nmol
      h-1 per 2 x 10(4) cells, whereas eight of the samples had a lower activity (1.05
      nmol h-1 per 2 x 10(4) cells on average) and five of the samples had a higher
      activity (6.53 nmol h-1 per 2 x 10(4) cells on average). The fluorometric
      determination of acid proteinase activity was found to be more reproducible and
      sensitive than the previously used spectrophotometric determinations.

PMID- 9009657
TI  - Increased prevalence of oral Candida albicans serotype B in homosexual men: a
      comparative and longitudinal study in HIV-infected and HIV-negative patients.
AB  - Several investigators have shown a comparatively high prevalence of Candida
      albicans serotype B among HIV-infected individuals. We serotyped oral C. albicans
      strains from 50 HIV-infected homosexual men, 39 HIV-seronegative homosexual men
      and 40 clinical oral isolates of a control group. The prevalence of serotype B
      was significantly higher in homosexual men, regardless of HIV serostatus, than in
      the control subjects. We suggest that the reported high prevalence of serotype B
      among AIDS patients in Europe and the USA simply reflects the high proportion of
      homosexual men among HIV-infected patients. In 22 subjects, oral C. albicans
      isolates were obtained at two or more time points, up to 8 years apart. No change
      in serotype was observed over time. The serotype prevalences in HIV-infected
      patients with oral thrush or AIDS-defining illness were similar to the group of
      homosexual men as a whole, indicating that there is no serotype-related variation
      in pathogenicity.

PMID- 9009658
TI  - A new pharmaceutical concept for the treatment of oropharyngeal and oesophageal
      candidosis with fluconazole.
AB  - Administration of fluconazole in capsule form has proved effective in the
      prophylaxis and treatment of mucosal candidosis, particularly in immunosuppressed
      patients. An additional topical effect in oropharyngeal and oesophageal
      candidosis might be expected with a fluconazole suspension. This hypothesis was
      therefore tested in a crossover study in 12 healthy volunteers in whom the
      concentrations of the antimycotic were measured in saliva and plasma after oral
      administration of 100 mg fluconazole as either a capsule or a suspension. The
      time courses of the fluconazole concentrations were very similar with the two
      formulations in plasma, but significantly different in saliva. Thus, the mean
      Cmax for fluconazole in saliva of 551 micrograms ml-1 was reached 5 min after
      ingestion of the suspension, compared with a value of 3 micrograms ml-1 some 4 h
      after taking the capsule. The mean concentration of the antimycotic in saliva
      over the observation period (0-96 h) was more than 80% higher with the suspension
      than with the capsule.

PMID- 9009659
TI  - Influence of zinc oxide on Aspergillus species: a possible cause of local, non
      invasive aspergillosis of the maxillary sinus.
AB  - Recently the appearance of radiopaque 'concrements' in the maxillary sinus was
      reported. These radiodense objects could be identified as root-filling material
      for teeth of the upper jaw containing zinc oxide. This suggested that excess root
      filling material containing zinc oxide in the maxillary sinus could favour the
      formation of a local, non-invasive aspergillosis. To verify this hypothesis in
      vitro, we tested the influence of zinc oxide on Aspergillus fumigatus, A. flavus,
      A. terreus, A. nidulans, A. niger and A. niveus. A geometric series of zinc oxide
      diluted in 0.1 N H2SO4 was used. Czapek-Dox agar was inoculated with the six
      Aspergillus species. Circular cavities stamped into the centre of each agar plate
      were filled with an equal amount of the dilutions and all plates were then
      incubated for 7 days at 37 degrees C. Readings were taken on days 3, 5 and 7.
      Soluble zinc oxide promoted the growth of all the tested Aspergillus species, the
      effect diminishing with decreasing concentration. This effect could be observed
      on all days of measurement. Only with A. niger was stimulation of growth minimal,
      probably because this species already exhibits a high growth rate on Czapek-Dox
      agar. Therefore, overfilling of maxillary teeth with a zinc oxide-containing root
      filling material may favour the formation of local aspergillosis.

PMID- 9009660
TI  - Non-value of Aspergillus antigen detection in bronchoalveolar lavage fluids of
      patients undergoing bone marrow transplantation.
AB  - A commercially available antigen assay (Pastorex Aspergillus) was used to detect
      Aspergillus antigen in serial bronchoalveolar lavage (BAL) fluids and sera of
      patients undergoing bone marrow transplantation (six patients with autopsyproven
      aspergillosis and 10 control patients without evidence of fungal infection).
      Aspergillus antigen was not detected in 17 BAL fluids of the six patients with
      proven aspergillosis. In two of the six patients the assay gave positive results
      in serum specimens. Three of the 10 control patients showed reactive BAL fluids.
      It is concluded that the latex agglutination assay of BAL fluids has no value in
      the diagnosis of invasive (pulmonary) aspergillosis in patients undergoing bone
      marrow transplantation.

PMID- 9009661
TI  - Tracheobronchial aspergillosis in a patient with AIDS treated with aerosolized
      amphotericin B combined with itraconazole.
AB  - The clinical features of a tracheobronchial infection due to Aspergillus flavus
      in an AIDS patient with a normal neutrophil count is described. Diagnosis was
      made by culture and microscopic examination of biopsies obtained from bronchial
      vegetations seen at bronchoscopy. Radiographic examination of the neck revealed
      the presence of large endoluminal fungal masses. Initially the patient was
      treated with a combination of itraconazole, flucytosine and aerosolized
      amphotericin B, then only with itraconazole plus aerosolized amphotericin B. A
      good therapeutic response was observed.

PMID- 9009662
TI  - Biological and sociocultural approaches of histoplasmosis in the State of
      Guerrero, Mexico.
AB  - Histoplasmosis is a deep mycosis with a high prevalence in America. Its
      aetiological agent, Histoplasma capsulatum, is found in Mexico, mainly in
      confined spaces, where it grows on bat guano or bird droppings. A research
      project has been developed in the State of Guerrero, Mexico, where many
      contaminated caves and mines are visited by individuals and epidemic outbreaks
      have been recorded. Data concerning human skin test response to histoplasmin
      antigen, host genetic predisposition to Histoplasma infection, sociocultural,
      socioeconomical and ethnobiological aspects of the disease in Guerrero are
      summarized in this paper.

PMID- 9009663
TI  - Subcutaneous mycosis in a cat due to Staphylotrichum coccosporum.
AB  - A 5.5-year-old, male, feline leucosis virus-positive cat developed a concurrent
      dermatophytosis due to Microsporum canis and a subcutaneous infection due to
      Staphylotrichum coccosporum. St. coccosporum caused mycetoma-like lesions. The
      fungal elements revealed features like those seen in phaeohyphomycosis. Until now
      St. coccosporum has been described to be non-pathogenic. The pathogenicity of St.
      coccosporum was corroborated by experimental infection.

PMID- 9009664
TI  - Human androgenic steroids affect growth of dermatophytes in vitro.
AB  - Hormonal effects on fungal growth are of particular interest to medical mycology.
      In the skin, androgenic steroids metabolized within pilosebaceous units may have
      direct effects on dermatophytes that invade hair follicles. In this study, 10(-1)
      to 10(2) mg 1(-1) testosterone, 5-alpha-dihydrotestosterone,
      dehydroepiandrosterone, androstenedione and androstanedione were used in agar
      dilution assays to test their effects on thallus diameters of Trichophyton
      rubrum, Epidermophyton floccosum, T. tonsurans, T. mentagrophytes and Microsporum
      canis. All dermatophytes responded in a dose-dependent manner with reduced
      diameters of thalli. Growth of T. rubrum and E. floccosum was completely or
      strongly suppressed by 10(2) mg 1(-1) androstenedione and androstanedione. A
      minor inhibition of all strains was obtained with 10(1) to 10(2) mg 1(-1)
      testosterone, dehydroepiandrosterone and 5-alpha-dihydrotestosterone, the last
      being least inhibitory for all species. Trichophyton mentagrophytes and M. canis
      were least responsive to most hormones. The high susceptibility of T. rubrum and
      E. floccosum to intrafollicular androstenedione and androstanedione could be one
      reason why these two species are unable to cause tinea capitis. Receptor-mediated
      effects and an unspecific interference with fungal sterol metabolism are
      discussed as mechanisms of fungal inhibition by steroidal hormones.

PMID- 9009665
TI  - Efficacy of ajoene, an organosulphur derived from garlic, in the short-term
      therapy of tinea pedis.
AB  - The present report shows the efficacy of ajoene, a garlic-derived organic
      trisulphur, for short-term therapy of tinea pedis. The use of ajoene as a 0.4%
      (w/w) cream resulted in complete clinical and mycological cure in 27 of 34
      patients (79%) after 7 days of treatment. The remaining seven patients (21%)
      achieved complete cure after seven additional days of treatment. All patients
      were evaluated for recurrence of mycotic infections 90 days after the end of
      treatment, yielding negative cultures for fungus. These results show that ajoene
      is an alternative, efficient and low-cost antimycotic drug for short-term therapy
      of tinea pedis. The fact that ajoene can be easily prepared from an alcoholic
      extract of garlic may make it suitable for Third World public health care.

PMID- 9009666
TI  - Tinea superficialis capitis due to Trichophyton soudanense in African immigrants.
AB  - Trichophyton soudanense is a common cause of tinea capitis in north-western
      tropical Africa. In European countries, infection seems to occur nearly
      exclusively in African immigrants and not in the indigenous population. From 1986
      to 1995 we obtained 7908 fungal cultures from patients undergoing treatment at
      the department of Dermatology in Aachen, Germany. During this period we observed
      eight cases of tinea capitis by T. soudanense in African immigrants aged 2-11
      years. One African immigrant suffered from tinea pedis and one German patient
      demonstrated tinea corporis attributed to T. soudanense. All cases responded well
      to local antimycotics in combination with systemic griseofulvin.

PMID- 9009667
TI  - Dermatophytoses in the Gdansk area, Poland: a 12-year survey.
AB  - A survey of dermatophytes and dermatophytoses was carried out among patients of
      the Department of Dermatology, Medical University of Gdansk, in the years 1984
      95. Over the 12-year period, 1195 cases of ringworm were seen: 55% in men and 45%
      in women. Listing the dermatophytes isolated and their frequencies as a
      percentage of the total are as follows: Trichophyton mentagrophytes 42.1%,
      Microsporum canis 26.0%, Trichophyton rubrum 14.7%, Epidermophyton floccosum
      11.0%, Trichophyton tonsurans 4.6%, Trichophyton verrucosum 1.3%, Trichophyton
      violaceum 0.3%. The most common clinical variant of dermatophytosis in the Gdansk
      area was tinea cutis glabrae (32.9%), followed by tinea pedis (24%),
      onychomycosis (16.5%), tinea capitis (11.9%)), tinea inguinalis (10.3%) and tinea
      manuum (4.4%). Dermatophytoses were significantly more frequent among adults (>
      15 years) (71.3%).

PMID- 9009668
TI  - Nutrition chemoprevention of gastrointestinal cancers: a critical review.
AB  - Various strategies utilizing specific dietary factors have been investigated for
      their ability to modulate the development of several cancers of the
      gastrointestinal tract. The effects of fat, red meat, fiber, fruits and
      vegetables, and alcohol on colorectal carcinogenesis have been reasonably well
      defined. Folate, selenium, and omega-3 fatty acids are rapidly emerging as
      important agents in nutrition chemoprevention, while the role of antioxidant
      vitamins and calcium is less certain. Although recent intervention studies from
      China have suggested a protective role of certain vitamins and minerals for
      esophageal and gastric cancers, further data from prospective randomized
      intervention studies are needed. Until more firm data are available, the dietary
      recommendations provided by the American Cancer Society and the National Cancer
      Institute are appropriate guidelines.

PMID- 9009669
TI  - Summary of the Surgeon General's report addressing physical activity and health.

PMID- 9009670
TI  - Discovery of the hemochromatosis gene will require rethinking the regulation of
      iron metabolism.
AB  - The identity of the protein responsible for hemochromatosis, the iron overload
      disease, has eluded scientists for years. However, a recent report identifies the
      gene where the hemochromatosis defect lies. It is a gene that encodes a major
      histocompatibility complex (MHC) class-1-like protein called HLA-H. The mechanism
      by which an HLA-H defect alters iron metabolism is still unidentified. However,
      this new discovery will certainly ignite a new wave of study into the physiology
      of iron metabolism and its regulation.

PMID- 9009671
TI  - Differential display PCR: a new age in nutrition investigation.
AB  - Molecular biology has provided nutrition science with a powerful experimental
      tool for exploring the molecular basis of essential nutrient deficiencies.
      Differential display polymerase chain reaction has emerged as an instrument of
      unlimited potential for assessing the manner by which nutrients regulate cell
      functions.

PMID- 9009673
TI  - Hearing results in tympanoplasty in Riyadh.
AB  - In patients with chronic otitis media, the aims of surgery are to eradicate
      middle ear disease, prevent recurrent infections, and improve hearing. In most
      published papers about tympanoplasty, the surgical approaches receive more
      attention as compared to hearing results. A total of 2015 ears with CSOM but
      without cholesteatoma, operated upon in a period of 9 years at King Abdul Aziz
      University Hospital, were studied and analyzed. The results showed 78%
      perforations closure rate, 19% reperforation rate, and 74% objective audiometry
      air-bone closure. The results of graft taking and closure of air-bone gap to
      within 10 dB were better using temporalis fascia compared to dura grafts. Post
      operative SNHL at 4000 KHz was more in cases using dura graft 6% compared with
      temporalis fascia 1.9%. Skill, experience, and development of medical facilities
      in distant areas in developing countries may prove helpful in improving the final
      results.

PMID- 9009672
TI  - Adipocyte differentiation is regulated by a prostaglandin liganded to the nuclear
      peroxisome proliferator-activated receptor.
AB  - Adipocyte differentiation and the homeostasis of fat cell number are regulated by
      a nuclear receptor protein, the peroxisome proliferator-activated receptor (PPAR
      gamma). The endogenous ligand is thought to be 15-deoxy-delta 12,14-prostaglandin
      J2-Thiazolidinedione, an antidiabetic drug, closely mimics the action of the
      prostaglandin, suggesting a regulatory role by the prostaglandin and PPAR gamma
      both in adipocyte differentiation and in glucose homeostasis.

PMID- 9009674
TI  - [Analysis of laryngeal cancer mortality in males in the Upper Silesia].
AB  - In the years 1985-1990 within Upper Silesia Region (Katowice Voivodeship) 25 696
      males died as the result of malignant neoplasms in total, in this, 1036, i.e.
      4.0% for larynx cancer. Every year died then average 173 men. Larynx cancer
      standardized mortality rates there are: 8.9 cases per 100 thousand on the whole
      area, maximal--21.4 and minimal--1.2 per 100 thousand (comparison between 45
      towns and 48 community councils). Larynx cancer mortality rates among males were
      dynamically increasing every year by 2.8%, what confirmed by the cohort analysis
      as well. There has not been obtained spatial correlation between highest larynx
      cancer mortality level and high ambient air pollution either.

PMID- 9009675
TI  - The effect of a pulsed magnetic field and that of methyl-silane triol on
      galactosamine induced hepatitis among rats.
AB  - Liver cell necrosis was induced in rats by a galactosamine injection. Cell death
      was due to an increase of Ca++ intracellular levels and was also under the
      control of genes. Rats were then either exposed or not to a 6 mT 100 HZ pulsed
      magnetic field (PMF) and they either received or not methylsilane-triol
      injections. Animals were sacrificed twenty-seven hours after a galactosamine
      injection. On the one hand it appeared from transaminase levels that the PMF
      increased the number of animals which were sensitized to galactosamine but
      decreased transaminase levels. On the other hand PMF decreased the protective
      effect of MST against galactosamine. We may suggest that PMF should be considered
      as an additional cellular signal received through genes which would determine the
      evolution towards or against apoptosis according to the age of the cell itself
      but also the Ca++ intracellular level.

PMID- 9009676
TI  - A twelve-month follow-up after Helicobacter pylori eradication. A clinical and
      histological evaluation.
AB  - To evaluate a twelve-month effect of Helicobacter pylori eradication, 258
      consecutive out-patients with H. pylori related active duodenal ulcer were given
      a ten-day eradicating treatment. After healing no maintenance antiulcer
      medication was given. On entering the study and then 2, 6 and 12 months after the
      completion of therapy patients were scored for symptoms and underwent endoscopy
      to assess the presence of duodenal ulcer and to score antrum and corpus
      gastritis. Statistical analysis was performed by means of the chi 2 test.
      Histological eradication, defined as the inability to detect H. pylori six months
      after the completion of the eradication course, was proved in 85 subjects while
      the 123 non-eradicated ones were considered as the control group. Ulcer relapse
      rate and ulcer-like symptoms were significantly less frequent among eradicated
      than non eradicated throughout the follow-up. As compared to non eradicated,
      gastritis significantly improved among eradicated in both antrum and corpus. H.
      pylori eradication may be recommended since, by reducing ulcer relapse rate and
      related symptoms, there is no need for further antiulcer maintenance therapy with
      a significant drop in socioeconomic costs.

PMID- 9009678
TI  - Urea disturbances in serum and urine of endurance trained volunteers during
      prolonged restriction of muscular activity.
AB  - The objective of this study was to determine the disturbances of urea in serum
      and urine of endurance trained volunteers during prolonged exposure to
      hypokinesia (decreased number of km/day). The studies during hypokinesia (HK)
      were performed for 364 days on twenty long-distance runners in the age of 23 to
      26 years, with an average peak oxygen uptake, of 66 ml.kg.min-1. All volunteers
      were divided into two equal groups: Ten volunteers were placed on a continuous
      regime of exercise 14.8 km/day and served as control subjects (CS). The remaining
      volunteers were subjected to continuous HK without the use of any preventive
      measures and were considered as the hypokinetic subjects (HS). For the simulation
      of the hypokinetic effect, the HS were kept continuously under an average of 2.7
      km/day for the duration of the study. Prior to exposure to HK, the HS were on the
      same exercise regime as the CS. During a 60 day pre-HK period and during the
      experimental period, urinary excretion of urea, creatinine, sodium, potassium and
      calcium and concentrations thereof in serum were measured. In the HS the
      concentrations of urea, creatinine, sodium, potassium and calcium in serum and
      the rate of excretion thereof in urine increased significantly when compared to
      the CS. It was concluded that prolonged restriction of muscular activity induces
      significant disturbances of urea in serum and urine of endurance trained
      volunteers.

PMID- 9009677
TI  - Evaluation of the efficacy and tolerability of four different therapeutic
      regimens for the Helicobacter pylori eradication.
AB  - The aim of our study is to evaluate the efficacy and tolerability of four
      different therapeutic regimens for Helicobacter pylori eradication. One-hundred
      and thirty-two consecutive patients suffering from either peptic ulcer or non
      ulcer dyspepsia, with Helicobacter pylori infection, were allocated to one of the
      following 4 groups with different therapeutic regimens: A) omeprazole 20 mg bid
      for 14 days/amoxycillin 1000 mg bid for 14 days/tinidazole 500 mg bid for 14 days
      (30 patients, 13 with peptic ulcer); B) omeprazole 20 mg bid for 14
      days/amoxycillin 1000 mg bid for 14 days (41 patients, 23 with peptic ulcer); C)
      omeprazole 20 mg bid for 14 days/azithromycin 500 mg/day for 3 days for 2
      consecutive weeks (25 patients, 12 with peptic ulcer); D) omeprazole 20 mg/day
      for 7 days/clarithromycin 250 mg bid for 7 days/tinidazole 500 mg bid for 7 days/
      (36 patients, 14 with peptic ulcer). The Helicobacter pylori status was evaluated
      by means of histology, culture and urease test, at entry and 8 weeks after
      treatment. 2 group A, B and D patients, 1 D patient didn't complete the
      treatment. In evaluable patients, the Helicobacter pylori eradication was
      obtained in 24 patients of group A (85.71%), in 24 of group B (58.98%), in 11 of
      group C (45.83%) and in 24 of group D (70.58%). On intention-to-treat analysis,
      Helicobacter pylori eradication was 80% in group A, 56.09% in group B, 44% in
      group D and 66.67% in group D. Sideeffects occurred in 6 patients of group A
      (20.68%), in 5 of group B (12.5%), in 3 group D (8.82%) and none of group C. In
      conclusion, triple therapy with omeprazole/clarithro-mycin/tinidazole is better
      for cost/benefit ratio; omeprazole/amoxycillin/tinidazole is more effective than
      others regimens in the Helicobacter pylori eradication, but causes more side
      effects; double therapy with omeprazole/azithromycin is the most tolerable and
      the least efficacy for Helicobacter pylori eradication.

PMID- 9009679
TI  - Tumour suppressor genes, immunology and local manifestations of neurofibromatosis
      phenotypes.
AB  - Research on Neurofibromatosis (NF) has been directed at understanding what
      determines disease quiescence, exacerbation, and the possible malignant
      evolution. Studies on NF have examined the role of genetic oncosuppression in the
      evolution of the defence against the non-self. Paraffin fixed specimens of benign
      and malignant neoplasia, occurring in patients with NF1 and NF2, were tested for
      the presence of p53: a reliable marker of genetic oncosupression. The wild type
      variant of p53 is expressed in malignant neoplasia, and is usually not expressed
      in benign tumors. Contrariwise, an immune reaction it is seen in benign tumors
      and is practically absent in malignant tumors. Evidence of protein p53 in the
      various malignant neoplasias studied by our group seems to reflect the up
      regulation on the oncosuppresive genetic potential that occurs while there is a
      lack of immunological defence. In the presence of an immunological defence, the
      expression p53 is normally not seen e.g. plexiform neurofibromas. The evolution
      of the various neoplastic types here reported was the same as that reported by
      current clinical and experimental models: the cell's defective genes are no
      longer suppressed and after activation the genes undergo initiation, promotion,
      and the cell sustains inflammatory-immune reactions that lead to fibrosis; what
      follows is a variable period of apparent quiescence. Severe pathogenic stimuli
      may act on predisposed cells and deteriorate pre-existing genetic damage, casting
      the cell into a phase of dysplastic or neoplastic proliferation that overcomes
      the body's defences. Hope for future therapy lies in the development of drugs
      that can either mimic the immune system or the proteins encoded by the
      oncosuppressor genes.

PMID- 9009680
TI  - Atherosclerotic femoral artery aneurysms: increase in deep femoral aneurysms?
AB  - Based on a clinical suspicion of an increase in the proportion of deep femoral
      aneurysms, we reviewed the case records of patients who underwent reconstructive
      procedures for femoral aneurysms to investigate if this could be confirmed and
      explained by selection of patient or modality of diagnosis. A study was made of
      17 atherosclerotic femoral aneurysms operations occurring in 17 patients from
      1989 to 1994. Eleven associated aneurysms were found. Eleven patients presented
      with an expanding swelling, 4 with rupture 3 with thrombosis and 2 were
      asymptomatic. Fourteen aneurysms involved the common femoral artery and 3 the
      deep femoral artery. The proportion of deep femoral aneurysm was therefore 3/17 =
      18%. Previous series report that aneurysms of the profunda femoris artery occurs
      in only 1% to 2.6% of all femoral artery aneurysms. No explanation was found for
      this significant increase (p < 0.05).

PMID- 9009681
TI  - Determination of antibodies to Borrelia burgdorferi in the serum of patients
      living in Calabria, southern Italy.
AB  - The aim of our work was to determine the sero-prevalence of antibodies to B.
      burgdorferi in 300 patients living in Calabria, a region of southern Italy. The
      research of antibodies to B. burgdorferi was conducted by ELISA as a screening
      method and Western Blot as a confirmatory test. Out of the 300 patients we found
      a rate of positivity of 7.3% with ELISA and 4.5% with Western Blot. This data
      allows us to classify Calabria, among the regions where Lyme borreliosis is non
      endemic and where sero-epidemiological research has been carried out on patients,
      as having a degree of positivity second to that of Campania (9.1%) and higher
      than Lombardy (3.2%) and Umbria (2.8%). Considering all the demographic and
      clinical data, only that of the higher IgG positivity of males over females is
      statistically significant.

PMID- 9009682
TI  - Prion-induced neuro-psychiatric syndromes.
AB  - Although further research is needed, the most recent thinking is that prions are
      tiny protein particles without DNA or RNA which have the ability to infect humans
      or animals. Prions cause slow infections which are fatal, experimentally
      transmissible, evoke no immune resistance from the infected host and are more
      resistant to disinfectants and chemical or physical agents than the other micro
      organisms that proliferate in the infected host. Update no evidence of possible
      passage by mouth from cows to men with consequent illness.

PMID- 9009683
TI  - Case report of a monoclonal gammopathy in a patient with chronic hepatitis:
      effects of beta-IFN treatment.
AB  - A sixty-one-year-old woman, with cirrhosis, presented with a monoclonal
      gammopathy of uncertain significance (MGSU). Often in a condition of cirrhosis is
      present a benign M component hypergammaglobulinemia. The electrophoresis and the
      immunophoresis showed a dense papraprotein in the gamma-region, an IgG with K
      light chain, an uncertain Bence-Jones proteinuria, a medullary plasmacytosis
      (9%), and a following growth of paraprotein were present. Lymphoblastic plasma
      cell were absent. Treatment with beta-IFN 6 MU for a period of six months and 3
      MU for a further period of three months proved ineffective for hepatic disease,
      but produced a quantitative reduction in gamma-G globulin, the Bence-Jones
      proteinuria was absent, a reduction in M component and in medullary
      plasmacytosis. Electrophoresis showed a polyclonal evolution of the gammopathy.
      Suspension of treatment was followed by de novo rise of monoclonal
      immunoglobulin. The authors report the use of beta-IFN in the therapy of multiple
      myeloma.

PMID- 9009684
TI  - Plasma cell leukemia. A report on 11 patients and review of the literature.
AB  - OBJECTIVE: Plasma-cell leukemia (PCL) is considered the leukemic variant of
      multiple myeloma. The diagnosis is based on plasmocytosis exceeding 2,000/mm3 and
      any evidence of clonal plasma cell proliferation. There are two forms of PCL: the
      primary form occurring in patients without preceding multiple myeloma or
      monoclonal gammopathy of undetermined significance, and the secondary form
      arising as a late manifestation in patients with multiple myeloma. Aim of the
      study was to describe our series of PCL and to report the main clinical and
      laboratory findings from the largest series in the literature. METHODS: Review of
      all cases of PCL observed from 1976 to 1994 in our Medical Divisions. Med-line
      research of the largest (more than 5 cases reports) series of PCL from 1969 to
      1994. RESULTS: Eleven cases of PCL were identified. We diagnosed 6 cases with
      primary PCL out of a total of 512 patients with monoclonal gammopathy (incidence,
      1.2%), 4 cases of secondary PCL as terminal phase out of 220 patients with
      multiple myeloma (incidence, 1.8%), and 1 case of secondary PCL as evolution of
      monoclonal gammopathy of undertermined significance out of 226 cases (incidence,
      0.4%). From our and literature review, that identified 203 cases of primary PCL
      and 157 cases of secondary PCL, the clinical and the laboratory features did not
      significantly differ between primary and secondary forms of PCL, whereas
      significant differences exist between the two forms regarding response to therapy
      and median survival. In our series, the mean survival was 14 months for primary
      PCL and 6.8 months for secondary PCL. Two of the 6 patients with primary PCL
      obtained a complete remission, with a duration of 28 and 23 months, respectively;
      only 1 patient with secondary PCL had a response to chemotherapy, with a
      remission of 6 months. CONCLUSION: Our observation and literature data indicate
      that PCL, both primary and secondary, is a very poor prognosis disease, that the
      response rate is higher with combination chemotherapy than single agents, and
      that primary PCL has a relatively better survival, since secondary plasma PCL
      usually shows resistance to any type of chemotherapy.

PMID- 9009685
TI  - The surgical treatment of vascular and gastrointestinal implications in Behcet
      disease. Report of four cases.
AB  - This study reports 4 cases of Behcet Syndrome which came under our observation
      and were surgically treated for vascular or gastrointestinal manifestations.
      These cases included 3 males and 1 female, mean age 26.5 years, of which 2 were
      treated with implantation of prosthesis for aneurysm of the abdominal aorta with
      recurrence of Behcet vasculitis and prosthesis substitution three years later in
      one case, 1 with total colectomy for ulcerous rectocolitis, while the last case
      (female) required excision and plastic reconstruction, for a perforated duodenal
      ulcer. Immediate and long-term results of the surgical treatment of the
      gastrointestinal and vascular manifestations and/or complications were
      satisfactory, whereas the long-term results of the medical treatment of the basic
      disease were unsuccessful in 50% of cases. BS is a rare affliction, whose
      pathogenesis is still poorly defined and in which the results of medical
      treatment cannot be regarded as satisfactory to date. Surgical treatment of its
      vascular and gastrointestinal manifestations and complications, on the other
      hand, was effective in our experience.

PMID- 9009687
TI  - Testicular feminization syndrome diagnosed in an elderly patient at surgery. A
      case report.
AB  - A case of Morris' syndrome in which the diagnosis has been realized only in old
      age is reported. A 69 year-old patient, with female external genitalia and
      secondary sexual characteristics, was referred to us with a diagnosis of a mass
      in the right inguinal region. Her personal history was based on a primary
      amenorrhoea, which was unsuccessfully investigated since she was adolescent. At
      the age of 63, during surgery for a left inguinal hernia realized in another
      hospital, a testis-like mass with the spermatic cord was casually found. During
      our hospitalization, a surgical removal of the right inguinal mass was performed,
      and the histologic examination showed the presence of a dominant sclerohyalin
      testicular tissue without evidence of seminal epithelium and sparse focuses of
      Leydig cells hyperplasia. Besides, the determination of gonadotropins and sex
      hormones yielded an increased production of LH, FSH, estradiol, testosterone and
      androstenedione. A cytogenetic analysis showed a 46, XY karyotype. The diagnosis
      realized only in old age has compelled the patient to live all her life, from
      sexual maturity, with indecision and doubt, and without a clinical explanation of
      fundamental utility even from the psychological point of view. Finally, in our
      patient the absence of cytologic aspect of malignant transformation in the
      removed testes in a six years period, seem fortuitous. It is always necessary to
      consider Morris' syndrome among the possible diseases causing primary amenorrhoea
      in the clinical evaluation of young phenotypic female patients.

PMID- 9009686
TI  - Ovarian pregnancies treated with methotrexate.
AB  - Medical therapy in ectopic and ovarian pregnancies in particular, can be a valid
      alternative to the surgical approach, since it can guarantee the reproductive
      function in a better way. More and more attempts with methotrexate, which can
      induce the death of both embryo and trophoblastic tissue, are being made. Both
      its administration and results are still under debate. In our case histories,
      three clinical cases are reported and two of them proved to be successful. In our
      opinion, apart from the method of administration, the prerequisites for a
      therapeutic success are: a small ovular sac (max 30 mm), no echographically
      visible embryo which corresponds to a six-week pregnancy. The success of the
      therapy, therefore, depends on the precociousness of the diagnosis.

PMID- 9009688
TI  - Suggested approach for end to side anastomosis to the abdominal aorta in aorto
      femoral bypass grafting for aorto-iliac occlusive disease.
AB  - For surgical treatment of aorto-iliac occlusive diseases the prosthetic grafts
      are used for aorto-femoral bypass in which the end to side anastomoses are done
      on anterior aspect of aorta. But this approach is leading to some disadvantages
      caused by gravity or pressure imposed by abdominal viscera and resulting to
      kinking to the anastomotic area between the vertebral column and viscera which
      brings about turbulence, platelet aggregation, thrombus formation, and its
      organization which finally occludes the lumen. Nazem's method of lateral end-to
      side anastomosis preferably to the left side of aorta will be without the
      mentioned bad on sequences, thereby greatly reducing mortality and morbidity. We
      recommend the interested academic groups use our method, which follows and we
      welcome them sharing their results with us.

PMID- 9009689
TI  - The Otto Loewi Lecture. Loewi's discovery and the XXI century.

PMID- 9009690
TI  - Molecular properties and cellular distribution of cholinergic synaptic proteins.

PMID- 9009692
TI  - Transcriptional regulation of the human choline acetyltransferase gene.

PMID- 9009691
TI  - Redistribution of clathrin and synaptophysin at the frog neuromuscular junction
      triggered by nerve stimulation: immunocytochemical studies of vesicle
      trafficking.

PMID- 9009693
TI  - Biosynthesis and integration of acetylcholinesterase in the cholinergic synapse.

PMID- 9009694
TI  - The VAChT/ChAT "cholinergic gene locus": new aspects of genetic and vesicular
      regulation of cholinergic function.

PMID- 9009695
TI  - Expression of the vesicular acetylcholine transporter in mammalian cells.

PMID- 9009696
TI  - Interactions of protons with the acetylcholine transporter of synaptic vesicles.

PMID- 9009697
TI  - Nicotinic receptors of the vertebrate CNS: introductory remarks.

PMID- 9009698
TI  - Nicotinic acetylcholine receptors on hippocampal neurons: cell compartment
      specific expression and modulatory control of channel activity.

PMID- 9009699
TI  - Structure and function of neuronal nicotinic acetylcholine receptors.

PMID- 9009700
TI  - 3-Heteroarylquinuclidin-2-ene derivatives as muscarinic antagonists: synthesis,
      structure-activity relationships and molecular modelling.

PMID- 9009701
TI  - Allosteric regulation of muscarinic receptors.

PMID- 9009702
TI  - Molecular aspects of muscarinic receptor assembly and function.

PMID- 9009703
TI  - Regulation of muscarinic acetylcholine receptor expression and function.

PMID- 9009705
TI  - Activation, cellular redistribution and enhanced degradation of the G proteins Gq
      and G11 by endogenously expressed and transfected phospholipase C-coupled
      muscarinic m1 acetylcholine receptors.

PMID- 9009704
TI  - The role of G-protein coupled receptor kinases in the regulation of muscarinic
      cholinergic receptors.

PMID- 9009706
TI  - Muscarinic receptors and cell signalling.

PMID- 9009708
TI  - Muscarinic activation of phosphatidylcholine hydrolysis.

PMID- 9009707
TI  - Muscarinic receptor activated Ca2+ channels in non-excitable cells.
AB  - We have provided preliminary characterization of a single channel Ca2+
      conductance in CHO cells. We have demonstrated that the channel conducts Ca2+, is
      regulated by m5 receptors, is voltage-independent, has an extremely low
      conductance, and is second messenger-independent. This channel may be the
      receptor-operated channel required for downstream activation of several signaling
      events. It is not known what other cell types express the channel or if it is one
      of a larger group of related channels. It seems likely that Ca2+ influx-dependent
      signaling pathways, activated by the muscarinic m5 receptor, would utilize a
      plasma membrane resident Ca2+ channel to provide a steady source of Ca2+ from
      outside the cell. The transient nature of IP3-activated increases in
      intracellular Ca2+ make it an unlikely source of the sustained Ca2+ rise required
      for phospholipase regulation. This is especially surprising, since levels of
      intracellular Ca2+ achieved from the release of intracellular Ca2+ stores can be
      at least one order of magnitude higher than those achieved from extracellular
      influx (Berridge, 1993). The phospholipase A2 and phospholipase D involved in
      muscarinic receptor-mediated signaling have not been purified or cloned. It is
      possible that receptor-activated and Ca2+ influx-dependent phospholipases are
      integral membrane proteins located adjacent to both receptors and channels. The
      phospholipases may also translocate to the membrane following activation where
      they would gain access to the continuous Ca2+ flow. Purification and cloning of
      this and other related channels should provide better insight into their role in
      cell signaling.

PMID- 9009709
TI  - Participation of small GTP-binding proteins in m3 muscarinic acetylcholine
      receptor signalling to phospholipase D and C.

PMID- 9009710
TI  - Modulation of acetylcholine release by nitric oxide.

PMID- 9009711
TI  - Presynaptic interactions between acetylcholine and glycine in the human brain.

PMID- 9009712
TI  - Purinergic regulation of acetylcholine release.
AB  - At the neuromuscular junction and possibly also at the synaptic level in the
      brain, the main sequence of events (see Fig. 5) that involves purines in
      modulation of ACh release includes the following observations: (1) storage of ATP
      and its release either together with, or independently of acetylcholine. ATP is
      also released from the post-junctional component. Adenosine as such is released
      either from the motor nerve terminals or from the post-junctional component. (2)
      There is extracellular hydrolysis of ATP to adenosine, which is the active
      substance to modulate transmitter release. The key enzyme in the conversion of
      AMP into adenosine is the ecto 5'-nucleotidase. When ecto-5'-nucleotidase is not
      available (e.g. in cholinergic nerve terminals of the cerebral cortex) ATP as
      such exerts the neuromodulatory role normally fulfilled by adenosine. (3) Both
      the inhibition and the excitation induced by adenosine on ACh release in the rat
      is inactivated through up-take and deamination. (4) Adenosine-induced inhibition
      of ACh release is mediated via A1 receptors and the excitation via A2a receptors.
      The A2a receptors are positively coupled to the adenylate cyclase/cyclic AMP
      system, whereas the presynaptic A1 receptors (a) may be negatively linked to
      adenylate cyclase and (b) to phospholipase C, and, upon stimulation, (c) increase
      potassium conductance and (d) decrease calcium conductance. (5) Activation of A2a
      receptors is essential for substances that facilitate ACh release (e.g. CGRP,
      forskolin) to exert their effects, as well as for induction of nicotinic
      autofacilitatory receptor desensitization. (6) There are interactions between A1
      and A2a receptors. Thus, the net adenosine neuromodulatory response is the
      resultant, at each moment, of the relative degree of activation of each one of
      these receptors. This relative activation depends upon the intensity (frequency,
      pulse duration) of stimulation of the motor nerve terminals. (7) Adenosine
      released as such seems to preferentially activate A1 receptors, whereas the
      adenosine formed from metabolism of adenine nucleotides prefers to activate the
      A2a receptors. In conclusion, to find out precisely what occurs with ACh in
      transmitting its message at the synaptic level, one has to consider the subtle
      ways used by purines to modulate the ACh response. It therefore appears of
      interest that pharmacological and therapeutic strategies use this knowledge to
      approach cholinergic transmission deficiencies based upon reduction of ACh
      release.

PMID- 9009713
TI  - Activity-related modulation of cholinergic transmission.

PMID- 9009714
TI  - Immunolesion by 192IgG-saporin of rat basal forebrain cholinergic system: a
      useful tool to produce cortical cholinergic dysfunction.
AB  - Cholinergic lesion paradigms have been used to study the role of the cholinergic
      system in cortical arousal and cognitive function, and its implication in
      cognitive deficits that occur in Alzheimer's disease. In the last few years an
      increasing number of studies have applied neurotoxins including excitotoxins or
      cholinotoxins (e.g. AF64A) by stereotaxic injection into the Nbm to produce
      reductions in cortical cholinergic activity. One of the most serious limitations
      of these lesion paradigms is the fact that basal forebrain cholinergic neurons
      are always intermingled with populations of noncholinergic cells and that the
      cytotoxins used are far from being selective to cholinergic cells. Excitoxins
      when infused directly into the Nbm destroy non-specifically cell bodies but spare
      axons passing the injection site, whereas the specificity of AF64A to destroy
      cholinergic neurons depends on both the dosage applied and the site of injection.
      Recently, a monoclonal antibody to the low-affinity nerve growth factor (NGF)
      receptor, 192IgG, coupled to a cytotoxin, saporin, has been described as an
      efficient and selective immunotoxin for the NGF-receptor bearing cholinergic
      neurons in rat basal forebrain. Intraventricular administration of the 192IgG
      saporin conjugate appears to induce a nearly complete and specific lesion of
      neocortical and hippocampal cholinergic afferents. Other neuronal systems in the
      basal forebrain are spared by the immunotoxin. Electrolytic, ibotenic acid, and
      cholinergic immunotoxic lesions of cholinergic basal forebrain nuclei resulted in
      slightly different effects on cortical cholinergic markers: Electrolytic lesion
      of the Nbm did not change M1-mAChR but resulted in reduced M2-mAChR in frontal
      and parietal cortices 1 week after lesion. Ibotenic acid lesion of the nucleus
      basalis did not alter M1-mAChR in any cortical region but led to enhanced M2
      mAChR binding in the parietal cortex only. When applying the cholinergic
      immunotoxin 192IgG-saporin, both M1- and M2-mAChR binding sites were increased in
      a number of cortical areas 1 week after lesion. This comparison suggests that
      possibly the destruction of non-cholinergic basal forebrain cells by ibotenic
      acid and electrolytic lesion, might partly contribute to these different cortical
      effects. NMDA receptor binding was markedly reduced and AMPA, kainate, and GABAA
      receptor binding has been significantly increased in cortical regions displaying
      a reduced activity of AChE and decreased levels of high-affinity choline uptake
      sites due to immunolesion of the basal forebrain cholinergic system. Equivalent
      changes in cortical glutamate and GABA receptor subtype levels have been observed
      7 days after electrolytic or ibotenic acid lesion of the Nbm. The data suggest
      that cholinergic immunolesion by 192IgG-saporin exhibits a valuable tool to
      produce specific cholinergic deficits in rats, which can be used as a model to
      study the effect of treatment with various drugs for compensating the impaired
      cortical cholinergic input.

PMID- 9009715
TI  - Cholinergic drug resistance and impaired spatial learning in transgenic mice
      overexpressing human brain acetylcholinesterase.

PMID- 9009716
TI  - Amyloid beta-peptides injection into the cholinergic nuclei: morphological,
      neurochemical and behavioral effects.

PMID- 9009718
TI  - Cholinomimetic treatment of Alzheimer's disease.

PMID- 9009717
TI  - The systems-level organization of cholinergic innervation in the human cerebral
      cortex and its alterations in Alzheimer's disease.

PMID- 9009720
TI  - Neurotrophic factors.

PMID- 9009719
TI  - New trends in cholinergic therapy for Alzheimer disease: nicotinic agonists or
      cholinesterase inhibitors?

PMID- 9009721
TI  - Development, survival and regeneration of rat cholinergic septohippocampal
      neurons: in vivo and in vitro studies.

PMID- 9009722
TI  - Effects of trophic factors on the CNS cholinergic phenotype.

PMID- 9009723
TI  - Synaptic modulation by neurotrophic factors.

PMID- 9009724
TI  - Neurotrophic factors for experimental treatment of motoneuron disease.

PMID- 9009725
TI  - The polymodal receptor: bio-warning and defense system.

PMID- 9009727
TI  - Sixty years of C-fiber recordings from animal and human skin nerves: historical
      notes.

PMID- 9009726
TI  - Cutaneous polymodal receptors: characteristics and plasticity.
AB  - The cutaneous sensory units labeled C-fiber polymodal nociceptors have a broadly
      coherent set of responsive characteristics. These include; (a) elevated
      thresholds to mechanical stimulation and to heat; (b) excitation by irritant and
      algesic chemicals; and (c) sensitization by injury or algesic substances. These
      characteristics and the match between the signals produced by C-polymodal
      nociceptors to pain-causing stimuli and human reports of pain indicate a probable
      causal connection. Nevertheless, there are indications that this population of
      sensory units may contain functionally-distinct subtypes. Some human C-polymodal
      nociceptors have been reported to be excited by histamine at low concentrations,
      whereas much of the population lacks such responsiveness. Further, in vitro
      studies of the effects of non-steroidal anti-inflammatory agents and low pH on
      sensitization suggest distinctions in the responsiveness of different elements
      whose general characteristics place them into the C-polymodal category. The
      enhanced responsiveness of C-polymodal nociceptors after heat stimulation or
      exposure to acidity has a probable relationship to the primary hyperalgesia
      produced after injury to hairy skin or in the presence of inflammation.
      Furthermore, the alterations of C-polymodal nociceptor characteristics after
      partial nerve injury and sympathectomy imply a change in phenotype of neurons
      spared by denervation and are suggestive of a possible relationship to
      sympathetically related pain and post-sympathetic neuralgias. These evidences of
      plasticity in responsiveness of a set of sense organs putatively associated with
      cutaneous pain represent lessons in the adaptability of biological mechanisms,
      and clues to the pathophysiology of pain.

PMID- 9009728
TI  - The articular polymodal nociceptor in health and disease.

PMID- 9009729
TI  - Group III and IV receptors in skeletal muscle: are they specific or polymodal?

PMID- 9009730
TI  - Visceral polymodal receptors.

PMID- 9009731
TI  - Modification of nociceptor responses by inflammatory mediators and second
      messengers implicated in their action--a study in canine testicular polymodal
      receptors.

PMID- 9009732
TI  - Tissue acidosis in nociception and pain.

PMID- 9009733
TI  - Sympathetic modulation of cutaneous polymodal receptors in chronically inflamed
      and diabetic rats.

PMID- 9009734
TI  - Interactions of sympathetic and primary afferent neurons following nerve injury
      and tissue trauma.
AB  - Sympathetic post-ganglionic neurons may be involved in the generation of pain,
      hyperalgesia and inflammation under pathophysiological conditions. Two categories
      of influence of the sympathetic neuron on afferent neurons can be distinguished
      and this distinction seems to be related to whether the coupling between afferent
      and sympathetic neuron develops after nerve lesion or after tissue trauma with
      inflammation (Fig. 15): A. Peripheral nerve lesion generates plastic changes of
      the afferent and sympathetic postganglionic neurons, depending on the type of
      nerve lesion (e.g. complete, partial). Both afferent and post-ganglionic neurons
      exhibit degenerative and regenerative changes and unlesioned neurons may show
      collateral sprouting in the periphery as well as in the dorsal root ganglion.
      This reorganization of the peripheral neurons may lead to chemical coupling
      between sympathetic and afferent neurons. The coupling is responsible for
      sensitization and/or activation of primary afferent neurons by the sympathetic
      neurons. The mediator probably is norepinephrine, but other substances cannot be
      excluded. The afferent neuron expresses or upregulates functional adrenoceptors.
      The type of adrenoceptor involved is probably alpha 2. The coupling may occur at
      different sites of the primary afferent neuron, e.g. at the lesion site, remote
      from the lesion site in the dorsal root ganglion or between nonlesioned
      sympathetic and afferent neurons which show collateral sprouting. The biochemical
      signals which trigger these changes probably are neurotrophic substances, their
      receptors which are synthesized by the peripheral neurons, Schwann cells and
      other cells in response to the peripheral lesions. B. Sympathetic nerve terminals
      in peripheral tissues may serve as mediator elements in hyperalgesia and
      inflammation following tissue trauma without nerve lesion. Experiments show that
      these functions are largely independent of activity in the sympathetic neurons
      and independent of vesicular release of transmitter substances (such as
      norepinephrine). Sensitization of nociceptive afferents for mechanical stimuli
      and venular plasma extravasation in the synovium which are induced by the
      inflammatory mediator bradykinin are, at least in part, dependent on the
      sympathetic terminal. The signal to venules and afferent receptors is synthesized
      and released from the sympathetic terminal or in association with it. It is a
      prostaglandin (probably PGE2). Sympathetically mediated (neurogenic) inflammation
      and neurogenic inflammation mediated by afferents may interact reciprocally and
      enhance the inflammatory process as well as the sensitization of nociceptive
      afferents. Norepinephrine may also lead to sensitization of nociceptive afferents
      under inflammatory conditions. This sensitization is presumably mediated by alpha
      2-adrenoceptors in the sympathetic varicosities and by a prostaglandin (probably
      PGI2) which is synthesized and released by or in association with the sympathetic
      varicosities.

PMID- 9009735
TI  - Human polymodal receptors in pathological conditions.

PMID- 9009736
TI  - Signal transduction in nociceptive afferent neurons in inflammatory conditions.

PMID- 9009737
TI  - Bradykinin B2 receptors and signal transduction analyzed in NG108-15
      neuroblastoma x glioma hybrid cells, B2 receptor-transformed CHO cells and ras
      transformed NIH/3T3 fibroblasts.

PMID- 9009738
TI  - Prostanoid receptors and signal transduction.

PMID- 9009739
TI  - Molecules relating to the neurogenesis of the sensory ganglion.

PMID- 9009740
TI  - The functional morphology of thin sensory axons: some principles and problems.

PMID- 9009741
TI  - Functional morphology of nociceptive and other fine sensory endings (free nerve
      endings) in different tissues.

PMID- 9009742
TI  - Neuropeptides in dural fine sensory nerve endings--involvement in neurogenic
      inflammation?

PMID- 9009743
TI  - Spinal organization of C-fiber afferents related with nociception or non
      nociception.

PMID- 9009744
TI  - Capsaicin-sensitive sensory nerve terminals with local and systemic efferent
      functions: facts and scopes of an unorthodox neuroregulatory mechanism.

PMID- 9009745
TI  - Neurogenic inflammation caused by cutaneous polymodal receptors.

PMID- 9009746
TI  - Peptides and cutaneous polymodal nociceptor neurones.

PMID- 9009747
TI  - Sensory afferent processing in multi-responsive DRG neurons.
AB  - The recent advance in molecular and neurobiological techniques disclosed the
      multi-responsive nature of DRG neurons. The survival, phenotype expression and
      electrical properties of these neurons are under the control of a variety of
      substances through their specific receptors. In pathological conditions, such as
      tissue inflammation or nerve injury, DRG neurons change their responsiveness
      through the dynamic reconstruction of their receptor system. This reconstruction
      is initiated by environmental stimuli. Thus the properties of polymodal
      nociceptors can be altered according to the environmental conditions. The whole
      story of this mechanism is not disclosed yet. In order to understand this
      mechanism, it is basically important to identify various receptor mRNAs in DRG
      neurons, precise localization of receptor proteins, site of synthesis and route
      of supply of ligands for these receptors.

PMID- 9009749
TI  - On the role of tachykinins and calcitonin gene-related peptide in the spinal
      mechanisms of nociception and in the induction and maintenance of inflammation
      evoked hyperexcitability in spinal cord neurons (with special reference to
      nociception in joints).

PMID- 9009748
TI  - Spinal cord mechanisms of hyperalgesia and allodynia: role of peripheral input
      from nociceptors.

PMID- 9009750
TI  - Slow synaptic transmission in the spinal dorsal horn.

PMID- 9009751
TI  - Plasticity of excitatory synaptic transmission in the spinal cord dorsal horn.

PMID- 9009752
TI  - Role of polymodal receptors in the acupuncture-mediated endogenous pain
      inhibitory systems.

PMID- 9009753
TI  - Modulations of autonomic functions by somatic nociceptive inputs.

PMID- 9009754
TI  - Convergent validity of select scales of the MMPI and the Achenbach Child Behavior
      Checklist-Youth Self-report.
AB  - The convergent validity of select clinical scales of the Minnesota Multiphasic
      Personality Inventory (MMPI) and the Achenbach Child Behavior Checklist-Youth
      Self-report was evaluated in a sample of 188 adolescent psychiatric inpatients.
      Clinical scales of the MMPI (Scales 1, 2, 3, 4, 8, and 0) and of the Youth Self
      report subscales of Somatic Complaints, Depressed, Aggressive, Delinquent,
      Thought Disorder, and Unpopular were selected for comparison based on their
      conceptual similarity. The extent to which scores for self-reported behavior on
      the Youth Self-report converged with scores on related clinical scales of the
      MMPI was evaluated by correlations and multiple regression. Concurrent validity
      for most comparisons between similar scales of the two measures was indicated and
      support the validity of the Youth Self-report as a self-report measure with an
      heterogeneous clinical sample of adolescents. The results establish a clear link
      between self-reported behaviors on the Youth Self-report and scores obtained on
      the select MMPI clinical scales which would conceptually be associated with those
      behaviors.

PMID- 9009755
TI  - Self-defeating personality, argumentativeness, and assertive self-statements.
AB  - 55 men and 55 women were administered Schill's Self-defeating Personality Scale,
      an argumentativeness scale, and a measure of assertive self-statements. Women
      with higher scores on the Self-defeating Personality Scale had lower scores on
      the argumentativeness scale. Both men and women scoring higher on the Self
      defeating Personality Scale recalled having thoughts which inhibited them from
      making assertive statements. These results were discussed as supporting prior
      research showing that persons reporting more self-defeating characteristics were
      relatively unassertive.

PMID- 9009756
TI  - The civilization of violence.

PMID- 9009757
TI  - Personality development of adolescents with hypogonadotropic hypogonadism.
AB  - Hypogonadotropic hypogonadism is a disorder of puberty characterized by absence
      of spontaneous sexual maturation. 8 male adolescents with this disorder, who were
      treated with pulsatile GnRH administration, were examined psychologically by
      means of standardized interviews. Problems were found in the development of
      independence (specifically relating to own body image and social functioning) and
      in identity development (particularly on personal characteristics).

PMID- 9009758
TI  - Evaluating a training program for parental educators.
AB  - This paper describes and evaluates a training program for parental educators to
      teach parenting classes for families with children 1 to 5 years of age. Six staff
      and parent volunteers from a family resource center participated. Evaluations of
      the training program showed improved knowledge and increased comfort in teaching
      parenting classes. Two graduates of the training program led a 10-week series of
      parenting classes. Parents in their class series (n = 9) significantly reduced
      their reported use of verbal and corporal punishment, increased their nurturing,
      and improved their perceptions of their children's behavior. These results were
      similar to those from a series of similar classes for 15 parents led by a
      university instructor. Results are discussed in terms of research needs for
      training qualified parental educators.

PMID- 9009759
TI  - WAIS-R profile variability of psychiatric inpatients.

PMID- 9009760
TI  - Use of inhalants among Miami's public school students, 1992.
AB  - This analysis examined inhalant use by 482 adolescents in Dade County, Florida
      public schools in 1992. Probit analysis indicated factors associated with
      increased probability of use included peers' use of inhalants, earlier grades
      (Grades 7 and 8), ready access, and a family member with a drug or alcohol
      problem. Adolescents were slightly more likely to use inhalants if they knew of
      the associated risks.

PMID- 9009761
TI  - Domestic integration and suicide in Spain.

PMID- 9009762
TI  - Comments on Scott and Ponsoda's (1996) positive and negative flashbulb memories.
AB  - Most of the events studied in flashbulb memory research are negative. Scott and
      Ponsoda (1996) are thoroughly commended for examining differences between
      positive and negative flashbulbs. Here we address three points. First, we note
      that other applicable research on autobiographical memory exists and stress that
      research on flashbulb memories should be prevented from becoming an isolated
      topic. Second, we identify some areas wherein flashbulb research has been
      applied, which help explain why there has been an imbalance towards negative
      events. Finally, we discuss some of the methodological difficulties matching
      positive and negative events.

PMID- 9009763
TI  - Does self-esteem predict suicidality after controls for depression?

PMID- 9009764
TI  - Breast feeding and children's intelligence.
AB  - Breast feeding was reported in 1992 by Lucas, et al. to provide advantages for
      the development of intelligence in children of low birth weight, possibly through
      nutrients or other biological factors found in human breast milk but not cow's
      milk. Research on breast feeding and intelligence in children of normal birth
      weight has yielded mixed results, probably because measurement of environmental
      influences has not been thorough and the range of intelligence components
      measured has been limited. Our research with 204 3-year-old children of normal
      birth weight included control measures for the environment and maternal
      intelligence (Hollings-head socioeconomic status, Home Observation for the
      Measured Environment, Shipley) and two measures of childhood intelligence
      (Stanford-Binet Fourth Edition and Peabody Picture Vocabulary Test-Revised).
      Controlling for environmental variables and maternal intelligence, initiation of
      breast feeding predicted scores on intelligence tests at age three. Breast
      feeding was associated with 4.6-point higher mean in children's intelligence.

PMID- 9009765
TI  - Being a "joiner" and psychological well-being.

PMID- 9009766
TI  - Bortner type A scores and eight basic emotions for survivors of ventricular
      fibrillation and left ventricular failure during acute myocardial infarction.
AB  - We examined Bortner scores for behavioral patterns and eight basic emotional
      dimensions named by Plutchik for patients with acute myocardial infarction who
      survived ventricular fibrillation and left ventricular failure. There were 70
      patients, 48 men and 22 women ages 26 to 69 yr. (M = 54, SD = 8), admitted to the
      coronary care unit within 24 hours of the onset of a long-lasting chest pain. Six
      patients survived an episode of ventricular fibrillation that occurred within 24
      to 48 hours after their admission. 15 patients developed left ventricular failure
      and were in Killip Classes II and III. Patients with acute myocardial infarction
      and left ventricular failure had mean Bortner scores significantly lower than
      others with acute myocardial infarction and were classed as Type B behavior.
      There was no difference in Bortner scores between patients with ventricular
      fibrillation and others with acute myocardial infarction. Patients with acute
      myocardial infarction and left ventricular failure scored significantly higher on
      Timid than others with acute myocardial infarction. Patients with acute
      myocardial infarction and ventricular fibrillation scored significantly lower on
      Depressed and higher on Distrust than other patients with acute myocardial
      infarction. Our findings suggest that patients with ventricular fibrillation and
      low scores on Depressed have good hospital prognosis. They are more critical and
      tend to reject people and ideas more than patients with acute myocardial
      infarction. This study suggests that the way in which patients with acute
      myocardial infarction react to their infarction, in terms of eight basic emotions
      and test patterns, is dependent on the complications of myocardial infarction.

PMID- 9009767
TI  - The Jungian psychological functions Sensing and Intuition and the preference for
      art.
AB  - The study investigated the relationship between the Jungian psychological
      functions Sensing (S) and Intuition (N) and preference for art. It was
      hypothesized that S-persons would prefer realistic and representational art,
      where N-persons would like abstract art. The Myers-Briggs Type Indicator was
      administered to 179 subjects to assess the preference for either the S- or N
      function. Subjects indicated how much they liked 20 painted portraits. The
      hypothesis was partly confirmed. Not only S-subjects (n = 100) but also N
      subjects (n = 79) prefer realistic paintings over abstract ones. On the whole,
      abstract paintings are valued less than realistic paintings, but N-subjects like
      abstract paintings more than S-subjects.

PMID- 9009768
TI  - A short measure of perceived empathy.
AB  - This paper concerns the development of a short measure of perceived empathy.
      Developed in the context of research on sales performance, the scale provided
      indicators for perceived empathy as both a cognitive as well as an affective
      construct. While not being able to differentiate cleanly between affective and
      cognitive empathy, the resulting single-factor scale demonstrates good internal
      consistency and validity, being predictive of successful versus unsuccessful
      sales encounters.

PMID- 9009769
TI  - Male nurses' sex-role orientation and values.
AB  - Scores on the Bem Sex-role Inventory and the Study of Values were compared for 66
      female nurses and 56 male nurses in central Florida. The men were frequently
      categorized as sex-typed and rarely as cross-typed. On the Study of Values the
      over-all pattern of values for male nurses was very similar to that of the
      average male nonnurse and significantly different from that of female nurses on
      the theoretical and aesthetic scales. Nursing experience, age, and highest degree
      earned in nursing were not correlated with Bem scores or Study of Values scores.
      No support was found for the idea that nursing feminizes male nurses.
      Implications of these results for the recruitment of male nursing students were
      discussed.

PMID- 9009770
TI  - Emotional states and perceived family functioning of caregivers of chronically
      ill children.
AB  - Emotional status and perception of family functioning of 32 primary caregivers of
      children with Battens disease was compared to 11 primary caregivers of children
      with chronic and less severe medical illnesses. The former caregivers were
      significantly more depressed, anxious, perceived their families as less cohesive
      and reported greater negative effects on their schedule and health than the
      latter group.

PMID- 9009771
TI  - Self-concept and locus of control among South African adolescents.
AB  - The present study explored the association of scores on self-concept Self
      description Inventory and locus of control (Academic Achievement Accountability)
      for 192 and 122 South African adolescent girls (M = 17.8 yr.) and boys (M = 19.0
      yr.), respectively. For the whole group rs ranged from .00 to .29, confirming
      that scores on a self-concept scale especially designed for South African
      adolescent girls and boys are weakly associated with scores on the locus of
      control scale.

PMID- 9009772
TI  - Interrater reliability of the written expression subtest of the Peabody
      Individual Achievement Test-Revised: an adolescent and adult sample.
AB  - This study examined the interrater reliability of the measure of written
      expression in the Peabody Individual Achievement Test-Revised. A sample more
      diverse in years of education and age than the normed population was used in this
      study. Fifty subjects from California, comprised of 72% females and 74%
      Caucasians, and ranging in age from 13 to 46, comprised the sample. Subjects were
      administered the "box" prompt from the PIAT-R Written Expression subtest (Level
      II). Interrater reliability for these scores was within the same range as the
      values provided in the manual once restriction of range was corrected.

PMID- 9009773
TI  - Further comments on psoriasis and personality disorders.
AB  - Fukunishi and Berger have recently criticized a paper on psoriasis by Rubino,
      Sonnino, Pezzarossa, Ciani, and Bassi. Their criticisms are analyzed and further
      data are presented, showing significantly higher frequencies of elevated scores
      on personality scales in patients with psoriasis, also when another dermatologic
      disfiguring condition (chronic urticaria) is taken as control.

PMID- 9009774
TI  - Association of identity and intimacy: an exploration of gender and sex-role
      orientation.
AB  - This study examined Erikson's psychosocial crises of identity versus identity
      diffusion and intimacy versus isolation, focusing specifically on how sex-role
      orientation contributes to gender differences in the resolution of these two
      crises. Perceptions of competence in self-disclosure and emotional support in
      both same-sex friendships and relationships with heterosexual dating partners,
      along with achievement of ideological and interpersonal identity, were included
      in the study so that differences could be examined. First-year and fourth-year
      college students (n = 135) at a large midwestern university responded to measures
      assessing identity, capacity for intimacy, and sex-role orientation. When
      controlling for sex-role orientation, the relationship between identity and
      intimacy was nonsignificant for men but significant for women.

PMID- 9009775
TI  - Prayer, church attendance, and personality revisited: a study among 16- to 19-yr.
      old girls.
AB  - A sample of 236 16- to 19-yr.old female A level students studying in the north
      east of England completed the short form Revised Eysenck Personality
      Questionnaire together with indices of prayer and church attendance. The data
      support the view that psychoticism is correlated with self-reported church
      attendance (r = -.15) and self-reported prayer (r = -.15), while scores on
      neither extraversion nor neuroticism are correlated with these indices of
      religiosity.

PMID- 9009776
TI  - Interpersonal consequences of narcissism.
AB  - This study explored the interpersonal consequences of different levels of
      narcissism in male and female targets. The Narcissistic Personality Inventory and
      its four subscales were given to compare interpersonal responses of persons
      exhibiting extreme, moderate, and low scores on narcissism. Participants read one
      of four versions of the inventory completed by a fictitious student named "Tom"
      or "Ann." Analyses indicated that, while gender of participant or target had no
      effect, participants expressed significantly less interest in further interaction
      and greater rejection of a person exhibiting extreme scores on narcissism than
      one with moderate scores, extreme scores on self-absorption and entitlement, and
      low narcissism scores.

PMID- 9009777
TI  - Reliability of the Weak Opiate Withdrawal Scale for inter-city opiate users.
AB  - The reliability (Kuder-Richardson 20) of the 84-item Weak Opiate Withdrawal Scale
      was estimated for a sample of 70 inner-city men who used opiates and had passed
      through the acute withdrawal stage. Analysis suggested modification of the scale
      to exclude negatively worded as well as cognitively sophisticated items which
      elicit unreliable and paradoxical responses from this population.

PMID- 9009778
TI  - Infanticide of defective newborns: an old midwife's story.
AB  - The story of how a midwife many years ago dealt with defective newborns is used
      to illustrate complete control by a system external to the family. Similarities
      exist with current public policy concerning the interrelated issues of abortion,
      neonatal euthanasia, and infanticide in which the family system is often ignored.
      It is argued that the family's values, expectations, and desires are relevant to
      the establishment of public policy in this sensitive domain.

PMID- 9009779
TI  - Profiles of Hispanic adolescents and adults on the Holland Themes and Basic
      Interest Scales of the Strong Interest Inventory.
AB  - The Strong Interest Inventory and its predecessors have been the subject of
      decades of research. Many studies have used Holland's Six General Occupational
      Themes, and some have explored the 23 Basic Interest Scales. The literature
      addresses IQ in vocational counseling and includes studies relating Holland's
      themes and the 23 interest scales. The subjects included a nationwide sample of
      894 13- to 65-yr.-olds tested during the standardization of the Kaufman
      Adolescent and Adult Intelligence Test. Multivariate analyses of variance were
      conducted with age, gender, and IQ on the intelligence test as independent
      variables, and the six Holland themes and 23 interest scales as dependent
      variables. IQ was related to Investigative and Artistic themes. Individuals with
      high IQs scored nearly one standard deviation higher than individuals with low
      IQs on each of these scales. A number of Basic Interest Scales correlated
      significantly with IQs, most of which were associated with either the
      Investigative or Artistic themes. Correlations of IQ with Holland Themes and
      scores on Basic Interest Scales were observed for both genders. The information
      gained from an individually administered intelligence test can enhance
      interpretation of the Holland themes and interest scales for vocational
      counseling.

PMID- 9009780
TI  - The prototypal view of diagnosis: predictive validity of diagnostic certainty for
      schizophrenia.

PMID- 9009781
TI  - Scores on the Wechsler Intelligence Scale for Children-Third Edition and Woodcock
      Johnson Tests of Achievement-Revised for a sample of children with emotional
      handicaps.
AB  - Because there is little available research, this study examined the associations
      between scores on the Wechsler Intelligence Scale for Children-Third Edition and
      the Woodcock-Johnson Tests of Achievement-Revised for 85 children with diagnosed
      emotional handicaps. Analysis indicated associations were significant.

PMID- 9009782
TI  - Is there psychopathology in the coparents of schizophrenic adoptees' half
      siblings?
AB  - An excess of schizophrenia has been observed in the biological relatives of
      adoptees with schizophrenia. The present analysis examined the possibility that
      illness observed among 90 half-siblings may have been influenced by assortative
      mating resulting in excess illness in the biological parents of the half-siblings
      not biologically related to the adoptees (the coparents). We found no difference
      in the prevalence of mental illness between 44 index and 26 control coparents.

PMID- 9009783
TI  - Personal conceptions of intelligence: a developmental study in Portugal.
AB  - The aim of this work is to present the results of a 2-yr. longitudinal study with
      a sample of 577 Portuguese high school students, observed twice, to study the
      intraindividual development of personal conceptions of intelligence during
      adolescence and its relation to school marks and to the causal dimension of
      controllability. Data, tested through LISREL structural equations, indicated
      school marks have an important role in the development of dynamic conceptions of
      intelligence during adolescence. These results were compared with those from
      other cultural contexts and were analysed in the context of Portuguese culture.

PMID- 9009784
TI  - The MMPI Suspiciousness Scale on the MMPI-2.

PMID- 9009785
TI  - Locus of control, sensation seeking, and stress.
AB  - We explored the relations among locus of control, sensation seeking, and stress
      (N = 68 students). Corroborating evidence was found that subjects with an
      external locus of control are more vulnerable to stress. Subjects scoring higher
      on the thrill and adventure seeking-dimension of sensation seeking reported less
      severe physical and psychological complaints thought to be associated with
      stress. These results suggest that high sensation seeking is associated with
      protective mechanisms against life-stress. Some possible intervening mechanisms
      are further discussed.

PMID- 9009786
TI  - Concurrent validity of the Work Addiction Risk Test as a measure of workaholism.
AB  - The Work Addiction Risk Test was administered, with a measure of anxiety and two
      measures of Type A behavior, to 363 undergraduates at a major southern
      institution to test for concurrent validity. Correlations of scores on the Work
      Addiction Risk Test with other scores support the scale as a valid measure of
      workaholism.

PMID- 9009787
TI  - Reduction of anxiety about death: need for beliefs about immortality.
AB  - It was hypothesized that individuals who are reminded of their own mortality will
      experience anxiety which is reduced by an increased need for belief in
      immortality. A questionnaire assessing the need for literal and two forms of
      symbolic immortality was developed. Analysis showed that awareness of mortality
      increased scores on the need for literal immortality but not on either form of
      symbolic immortality.

PMID- 9009788
TI  - Jealousy induction as a predictor of power and the use of other control methods
      in heterosexual relationships.
AB  - 26 male and 87 female college students filled out Stets' Psychological Aggression
      Scale, Stets' Interpersonal Control Scale, Straus' Physical Violence Scale, and
      Fisch and Brainerd's Use and Approval of Jealousy-inducing Behaviors Scale. Use
      and approval of jealousy-inducing behaviors were good predictors of high need for
      interpersonal control and the use of psychological aggression. The use of
      jealousy-inducing behaviors but not the approval of these behaviors was a strong
      predictor of physical aggression in romantic relationships.

PMID- 9009789
TI  - Perceived family-of-origin health and current adjustment.

PMID- 9009790
TI  - Risk perceptions in Australia.
AB  - Research on perceptions of risk in Australia began only recently. Typically, data
      from other countries were used to determine what hazards might be considered most
      and least risky by the Australian public. Relying on overseas data is
      problematic, however, because cultural contexts may influence risk perceptions.
      To address the paucity of data on risk perceptions in Australia, we obtained
      relative risk ratings for 30 hazardous technologies and activities from 40
      Australian undergraduate students. The results suggested that, while there are
      some similarities with other countries, there are also some unique features in
      Australian risk perceptions. Researchers should investigate the reasons
      underlying similarities and differences in risk perceptions across cultures.

PMID- 9009791
TI  - Expression of anger by Samoan adults.
AB  - A modified version of Spielberger's 1988 Anger Expression Inventory including
      four Samoan culture-specific anger terms was administered to 593 adult American
      and Western Samoans, 25 to 55 years, to assess intrasample age, sex, and location
      differences and to examine its cross-cultural utility by an exploratory factor
      analysis. American Samoans men's and women's scores showed greater difficulty
      controlling anger than Western Samoan men and women, American Samoan males scored
      higher on Anger-Out and Samoan anger expression than Western Samoan men, and
      Western Samoan women scored higher on Anger-Out and higher on Samoan anger
      expression than Western Samoan men. Factor analysis showed that Spielberger's
      original factor structure was replicated in all subpopulations except American
      Samoan women. Control of anger, a Samoan cultural core value, appears to be more
      difficult in modern American Samoans of both sexes compared with the more
      traditional Western Samoans. Among American Samoan women, we speculate that role
      expansion may be responsible for their heterogeneous factor structure of anger
      expression.

PMID- 9009792
TI  - Self-esteem and caregivers' attitudes toward elderly persons.
AB  - A scale identifying 141 medical students who responded positively to geriatric
      patients was based on Rosenberg's Self-esteem Scale modified by adding a phrase
      about geriatric care. Personal and professional role traits that predicted a
      positive therapeutic attitude were high scores on social desirability or self
      monitoring and low scores on thanatophobia and depression. Senior medical
      students who expressed the highest self-esteem toward caring for elderly people
      indicated family medicine as their first choice of residency.

PMID- 9009793
TI  - Predictors of paternal involvement and satisfaction.
AB  - Few researchers have simultaneously examined the multiple components of
      fathering, attitudes, practices, involvement, and satisfaction. Consequently,
      there is little information available concerning the empirical relations among
      these dimensions of fathering and of the theoretical meanings implied by these
      relations. 177 fathers of firstborn sons and daughters, ages 4, 8, 12, and 16
      years, were administered structured standardized questionnaires assessing their
      childrearing practices, attitudes, involvement, and satisfaction. Multiple
      regression analyses identified several significant predictors of paternal
      involvement across the four age groups, including demographic variables and
      childrearing practices. Analyses conducted within each age group yielded somewhat
      different regression models. Implications for research on fathering and parental
      education programs are discussed.

PMID- 9009794
TI  - The modal study on premenstrual syndrome or tension: a content analysis of 315
      recent abstracts along global dimensions.
AB  - From 315 abstracts from Psychological Abstracts (January 1990-February 1996), the
      modal current study dealing with premenstrual syndrome or tension has a within
      subjects design and includes 20 to 80 nonpathological subjects. Conclusions based
      on prospective self-reports are that negative psychological and somatic ratings
      increase premenstrually or menstrually and that changes are more pronounced (and
      scores higher) for groups who are identified with symptoms.

PMID- 9009795
TI  - Identifying patients recovering from a recent myocardial infarction who require
      and accept psychological care.
AB  - Using Dutch adaptations of the State-Trait Anxiety Inventory, State-Trait Anger
      Scale, Zung Depression Scale, and Life Orientation Test, we attempted to identify
      which patients recovering in the hospital from acute myocardial infarctions
      required and would accept psychological care. Of 63 patients who completed the
      relevant questionnaires, 9 required and accepted psychological care and 6 of
      these were correctly predicted by the criteria (sensitivity = .67). Of the 54
      patients not classified as requiring and accepting psychological care, 49 were
      correctly predicted (specificity = .90; efficiency = .87). Noncompletion (n = 7)
      was positively associated with classification as requiring and accepting
      psychological care. An easy to administer brief questionnaire may help identify
      those patients with a recent myocardial infarction who, in the opinion of mental
      health care professionals, require and accept psychological care.

PMID- 9009796
TI  - Word frequency affects hypermnesia.
AB  - Hypermnesia, the tendency of participants to recall more items from a list they
      have studied when they are asked to recall the list several times on a free
      recall test, is enhanced by factors that lead to better performance on free
      recall tests. This study tested the hypothesis that words which appear with high
      frequency in the English language would produce hypermnesia but that low
      frequency words would not. The activity the 57 participants were required to do
      between repeated recall tests was also manipulated but had no effect on the
      number of words recalled. High frequency words resulted in hypermnesia but low
      frequency words did not.

PMID- 9009797
TI  - Meta-analysis with longitudinal studies: controlling for analytical bias.
AB  - A recent study published in an international medical journal presented an
      opportunity to demonstrate the difficulties of interpreting meta-analysis results
      with longitudinal data. We conducted a new meta-analysis using identical data
      from the published study and showed contradictory results.

PMID- 9009798
TI  - Quality of care and cost-containment in managed mental health: policy, education,
      research, advocacy.
AB  - Managed mental health care cost-containment practices of risk-benefit analysis,
      provider usage, manipulation of supply and demand, gate keeping, medical
      necessity, and formulation have adversely affected quality of care. Improved
      mental health services are dependent upon redefining mental health problems and
      understanding inequities created by medicalization as means to limit access to
      services. This dilemma can be addressed by development of mental health policy,
      public education, and political advocacy. An immediate role for professional
      psychology is found in the creation of a research agenda that documents
      empirically supported interventions for specific mental health problems,
      mechanisms of effective and acceptable service-delivery, and identification of
      providers with demonstrated clinical skills, including cultural competencies.

PMID- 9009799
TI  - Co-sleeping: gender differences in college students' retrospective reports of
      sleeping with parents during childhood.
AB  - 161 women and 111 men, Caucasian college students, provided retrospective
      information about their patterns of sleeping during childhood. The practice of co
      sleeping was common, with 33.7% reporting that they co-slept in their parents'
      room during their first week after birth, 29.4% during the first month after
      birth, and 27.5% during their second month after birth. In addition, 6.3% of
      women and 11.9% of men reported that they co-slept during the entire first year
      after birth. Finally, a sex-specific pattern of co-sleeping was found with more
      women reporting that they co-slept with their parents during their first week and
      first month after birth, but a greater percentage of men than women reported that
      they co-slept with their parents at older ages. It appears that girls are removed
      from the parents' room at a younger age and more frequently than are boys.

PMID- 9009800
TI  - A preliminary study on the prevalence of challenging behaviours.
AB  - The purpose of this study was to estimate the prevalence of challenging behaviour
      among subjects with learning disabilities in an English health district.
      Subjects' disabilities included incontinence, lack of communication skills, and
      need of assistance with domestic activities, feeding, washing, and dressing. Some
      also had physical impairments. The most common behaviours were hyperactivity and
      irritability and the most common psychiatric disorders included severe anxiety,
      affective disorder, and adjustment disorder.

PMID- 9009801
TI  - Effects of teacher assistance teams on special education referrals in elementary
      schools.
AB  - School-based problem-solving teams recently have received much attention as a
      possible support for children who are at risk for school failure and for over
      referral to special education. However, no controlled studies of the effects of
      such teams on numbers of referrals for special education or for proportion of
      appropriate referrals for special education have been conducted. The lack of
      adequate research concerning school-based problem-solving teams, coupled with the
      widespread promotion of their use, suggests that further study of such teams is
      important. In this study, we investigated the effect of one team model, Teacher
      Assistance Teams, on special education referrals in elementary schools of a large
      urban district. To address limitations of previous research, schools with such
      teams were compared with those without across several years of implementation.
      Analysis yielded a significant decrease in referrals in both groups of schools
      but no significant differences between groups. These findings may be explained by
      the context in which both groups of schools functioned.

PMID- 9009802
TI  - Probe P3 and blinks: two measures of affective startle modulation.
AB  - Two concurrent measures of the evoked startle response, the elicited blink reflex
      and the event-related potential, were measured while individuals viewed pictures
      that varied in pleasure and arousal. Replicating previous findings, the blink
      response was modulated by picture pleasantness, with larger reflexes elicited in
      the context of viewing unpleasant versus pleasant pictures. However, the probe P3
      was primarily modulated by picture arousal, with smaller P3 responses elicited
      when viewing affective (pleasant or unpleasant) than when viewing neutral
      pictures. Both modulatory effects were sustained for probes presented in a
      subsequent picture imagery period. These data suggest that two measurable
      responses to the same startle probe are differentially modified by emotional
      context, with blink magnitude varying with pleasure and probe P3 varying with
      stimulus arousal.

PMID- 9009803
TI  - Localization of word and face recognition memory using topographical EEG.
AB  - The aim of this study was to explore the ability of epoch-averaged
      electroencephalogram (EEG) to localize cognitive functions. The EEG was recorded
      in healthy individuals performing a task where, on the basis of evidence from
      other functional brain imaging techniques, there was a high expectation of where
      functional changes would be expected. Topographical EEG was recorded while
      individuals performed recognition memory tasks for words and faces. Comparison of
      the acquisition and recognition phases of the experiment showed significant
      attenuation of alpha, beta 1, and beta 2 in the right temporoparietal region for
      the faces but no significant changes for words. Left temporoparietal changes for
      the word task were only seen among the women. The results confirmed the validity
      of EEG for use in the localization of cognitive function for faces for men and
      women but in the case of words for the women only.

PMID- 9009804
TI  - The pupillary light reflex cannot be used to measure sleepiness.
AB  - The pupillary light reflex (PLR) has been considered by some researchers to be
      responsive to changes in levels of sleepiness. However, no previous studies have
      tested this hypothesis with the dramatic variation of sleepiness across a
      complete circadian cycle. In this experiment, 20 normal individuals (age: 18-48
      years) underwent a 27-hr constant routine, during which they were kept awake
      except for a 15-min nap opportunity every hour. Sleepiness was assessed both
      subjectively, by the Stanford Sleepiness Scale, and objectively, by a modified
      version of the Multiple Sleep Latency Test. The PLR in response to a flash of
      light was recorded every 2 hr, immediately before a nap period. Results showed
      that baseline pupil diameter became smaller with progressive sleep restriction,
      but there were no changes in any of the parameters of the PLR despite significant
      fluctuations in sleepiness. Some of the changes in the PLR were significantly
      related to changes in baseline pupil diameter. When baseline diameter was
      partialled out, there was still no effect of sleepiness on the PLR. The results
      suggest that the PLR cannot be used as a measure of sleepiness.

PMID- 9009805
TI  - Affective modulation of tactile startle.
AB  - Two studies were conducted to investigate affective modulation of startle
      responses to unilateral tactile probes and to determine whether such modulation
      is lateralized. Right-handed undergraduates received airpuffs to the left or
      right temple while viewing pleasant, neutral, and unpleasant pictures. Side of
      probe presentation was varied between the two trial blocks of the experiment in
      Study 1 (n = 48) but varied randomly within trial blocks in Study 2 (n = 48).
      Primary results were consistent across studies. Replicating and extending the
      findings for acoustic probes, eyeblink responses to tactile probes were larger
      during unpleasant than during pleasant pictures. However, affective modulation of
      startle did not differ reliably between the two sides of probe presentation
      (sensory laterality) or the two sides of the response (motor laterality) in
      either study or in a combined analysis.

PMID- 9009806
TI  - Temporal prominence of auditory evoked potentials (N1 wave) in 4-8-year-old
      children.
AB  - Cortical auditory evoked potentials (N1 wave) were studied in 24 adults (12 men,
      12 women) and 20 children (12 boys, 8 girls; age: 4-8 years). In adults, this
      wave was recorded with maximal amplitude at frontocentral sites, peaking at about
      100 ms poststimulation, whereas in children the auditory response displayed
      maximal amplitude at the midtemporal sites, with a positive wave at about 100 ms
      and a large negative wave at approximately 170 ms. Moreover, the modulatory
      effects of intensity on N1 amplitude were prominent at frontocentral sites in
      adults and at temporal sites in children. Frontocentral negative response was
      also recorded in children but was smaller in amplitude and longer in peak latency
      (around 140 ms) than in adults; responses were of greater amplitude at the
      frontal site than at the vertex before 6 years of age, whereas the reverse was
      more often found after this age. These data suggest great differences with age in
      the neural generators contributing to auditory evoked potentials recorded in the
      N1 latency range.

PMID- 9009807
TI  - Autonomic patterns during respiratory suspensions: possible markers of
      Transcendental Consciousness.
AB  - In two experiments, we investigated physiological correlates of transcendental
      consciousness during Transcendental Meditation sessions. In the first,
      experimenter-initiated bells, based on observed physiological patterns, marked
      three phases during a Transcendental Meditation session in 16 individuals.
      Interrater reliability between participant and experimenter classification of
      experiences at each bell was quite good. During phases including transcendental
      consciousness experiences, skin conductance responses and heart rate deceleration
      occurred at the onset of respiratory suspensions or reductions in breath volume.
      In the second experiment, this autonomic pattern was compared with that during
      forced breath holding. Phasic autonomic activity was significantly higher at
      respiratory suspension onset than at breath holding onset. These easily measured
      markers could help focus research on the existence and characteristics of
      transcendental consciousness.

PMID- 9009808
TI  - P300 event-related potential heritability in monozygotic and dizygotic twins.
AB  - The present study examined the heritability of the P3 waveform and the N1, P2,
      and N2 components by assessing the visual event-related potential (ERP) of 30
      monozygotic (MZ) and 34 dizygotic (DZ) twin pairs. Electroencephalogram activity
      was recorded from Pz, P3, and P4 scalp sites while individuals performed a
      reaction time task involving two conditions differing in difficulty. Genetic
      modeling indicated substantial genetic influence on P3 amplitude, P3 latency, and
      manual reaction time for the difficult condition. No significant heritability was
      found for the latency of P3 or manual reaction time for the easy condition, but
      P3 amplitude was heritable for this condition. The amplitude of the early
      components (N1, P2, and N2) was heritable, but no significant genetic influences
      were found for the latency of these components. Compared with the DZ twins, the
      greater similarity of the MZ pairs on the event-related potential measures was
      not due to their greater similarity in either head dimensions or mental ability,
      despite the facts that IQ scores were weakly correlated with P3 and N2 amplitude
      and that amplitude and latency were related to some measures of head size. These
      findings suggest that P3 amplitude and the amplitude of earlier ERP components
      are under partial genetic control, supporting the notion that these ERP
      components could perhaps be used to identify genetic risk for psychopathology.

PMID- 9009809
TI  - Allocation of attentional resources during habituation to food cues.
AB  - Two experiments were designed to test the hypothesis that habituation to repeated
      food cues can be inhibited by allocating processing resources to nonfood cues. In
      two experiments, the salivary response to 10 presentations of lemon yogurt was
      assessed while subjects engaged in a controlled cognitive search task (demanding
      attentional resources), an automatic search task (needing fewer attentional
      resources), or no task. In Experiment 1, the controlled and automatic search
      tasks differed in the number of memory set items. In Experiment 2, the size of
      the memory sets was held constant, and individuals were provided practice to
      stabilize the different search strategies in the task. The automatic search and
      no task groups habituated to the repeated presentation of food cues in both
      experiments, but the controlled search group did not. These results support the
      hypothesis that allocation of attentional resources to external cues can
      influence the processing of food cues.

PMID- 9009810
TI  - Social determinants of cardiovascular reactivity: effects of incentive to exert
      influence and evaluative threat.
AB  - The effects on cardiovascular reactivity of incentive to influence the judgements
      of the experimenter and the threat of social evaluation were examined in a sample
      of 60 male and 60 female undergraduates. Participants either were guaranteed
      $5.00 to prepare and deliver a brief speech or were told that the money was
      contingent on an evaluation by the experimenter. Participants believed that their
      speech would be rated for either simple clarity or verbal intelligence. The
      contingent incentive increased systolic blood pressure reactivity by 6.5 mmHg
      (32%). Evaluative threat increased systolic reactivity by 7.1 mmHg (36%). These
      interpersonal processes could increase the risk of cardiovascular disease and are
      likely to affect the degree of cardiovascular reactivity in laboratory studies.

PMID- 9009811
TI  - An ERP analysis of implicit structured sequence learning.
AB  - When task exposure facilitates performance without producing corresponding
      changes in verbalizable knowledge, learning is said to be implicit. In Experiment
      1, event-related potentials (ERPs) were recorded as individuals practiced an
      implicit structured sequence learning (ISSL) task wherein only some target events
      required a response. With practice, the ERPs to targets that obeyed the
      underlying grammar diverged from those that did not at around 200 ms; grammatical
      targets appeared to be more positive between 200 and 500 ms because a similar
      positivity for the ungrammatical targets was delayed. In Experiment 2, the
      grammar was simplified allowing a direct comparison to be made between an
      implicit learning group and an explicit group, who were taught the grammar prior
      to recording. The results of the comparison revealed a remarkable similarity but
      did implicate at least partially nonidentical neural mechanisms in implicit and
      explicit structured sequence learning.

PMID- 9009812
TI  - Relationships between startle and cardiovascular reactivity.
AB  - Although startle and cardiovascular reactivity have been studied extensively,
      little is known about their relationship. In the present study, we examined
      cardiovascular responses and affective startle modulation in 112 normotensive
      individuals varying in self-reported fearfulness and parental cardiovascular
      health history. An initial intense noise burst elicited a phasic cardiac
      acceleration that was larger for fearful individuals. Startle blink responses
      were larger during aversive than during pleasant relaxing imagery but did not
      differ with fear group. Cognitive challenge tasks elicited heart rate and blood
      pressure increases that were unrelated to fearfulness or parental health history.
      However, greater startle potentiation by aversive imagery predicted larger
      pressor responses to cognitive challenge, especially among men. The observed
      relationship between startle and cardiovascular reactivity suggests a common
      mechanism for their affective modulation.

PMID- 9009813
TI  - Fear and the startle reflex: blink modulation and autonomic response patterns in
      animal and mutilation fearful subjects.
AB  - The present study was designed to examine the pattern of startle reflex
      modulation and autonomic responses for individuals high in animal or blood-injury
      fear when viewing pictures of their feared objects. Sixteen individuals in each
      fear group and 16 low-fear control individuals viewed 32 color slides depicting
      fear-relevant, unpleasant but fear-unrelated, neutral, and pleasant scenes. Free
      viewing times were assessed in a second phase of the procedure as an index of
      avoidance behavior. Exposure to pictures of feared objects resulted in a
      consistent startle reflex potentiation and behavioral avoidance in both fear
      groups. This activation of the basic aversive system was independent of the
      autonomic pattern of the fear responses, which differed for the high-fear groups.
      These results suggest that the probe startle response indexes the organism's
      basic motivational disposition and add new information to the assessment of fear.

PMID- 9009814
TI  - The role of comparison questions in physiological detection of deception.
AB  - Comparison questions in physiological detection of deception were studied with 60
      "guilty" and 60 "innocent" participants in a mock crime experiment. Different
      types of comparison questions were used in four conditions: relevant-irrelevant
      (R-I) participants answered only relevant and neutral questions; trivial directed
      lie participants were instructed to lie to three of the six neutral questions;
      personal directed lie participants were instructed to lie to personally relevant
      questions; and probable lie participants received traditional probable lie
      comparison questions. Respiration, cardiovascular, vasomotor, and electrodermal
      activity were recorded. Manipulation of the comparison questions produced
      different patterns of physiological responses for innocent but not for guilty
      participants. The R-I test produced an unacceptable rate of false positive
      decisions.

PMID- 9009815
TI  - Psychophysiological response of ADHD children to reward and extinction.
AB  - In this study, we examined heart rate and skin conductance levels of 18 children
      with attention-deficit hyperactivity disorder (ADHD) and 18 normal children as
      they performed a repetitive motor task during reward and extinction conditions.
      Fowles (1980, Psychophysiology, 17, 87-104; 1988, Psychophysiology, 25, 373-391)
      suggested that psychophysiological responsivity reflects activity in two of
      Gray's (1982, The neuropsychology of anxiety, Oxford University Press; 1987, The
      psychology of fear and stress, Cambridge University Press) motivational systems;
      heart rate reactivity during reward reflects activity in the behavioral
      activation system, and skin conductance reactivity during extinction reflects
      activity in the behavioral inhibition system. As predicted, control children
      showed increased heart rate when reward was present and increased skin
      conductance when reward was removed. Compared with controls, ADHD children failed
      to show increased skin conductance levels during extinction, suggesting a weak
      behavioral inhibition system. ADHD children also displayed faster heart rate
      habituation to reward.

PMID- 9009816
TI  - A plethysmographic method for demonstrating the response specificity of the oral
      vascular bed.
AB  - In this paper, we describe a new method for measuring the oral plethysmogram, and
      we assess its sensitivity and specificity under differing psychological
      stimulation. Finger and palate pulse amplitudes and blood pressure were monitored
      while individuals (N = 13) performed several tasks: mental arithmetic, nausea
      imagery, fear imagery, and anger imagery. Pulse pressure, having a major effect
      on pulse amplitude, was partialed out in analyses. Palate pulse amplitude
      increased significantly in response to the degree to which the individual felt
      irritated, judged, nauseated, or angry. In contrast, finger pulse amplitude
      changed significantly only in the arithmetic task and, unlike the palate, showed
      a decreased amplitude with increased irritation and being judged. Results
      indicate that the oral plethysmogram can serve as a reliable measure of oral
      mucosal vasomotor reactivity and that it has a different pattern of response
      specificity than does the finger.

PMID- 9009818
TI  - Wilsonian methods of concept analysis: a critique.
AB  - Wilsonian methods of concept analysis--that is, the method proposed by Wilson and
      Wilson-derived methods in nursing (as described by Walker and Avant; Chinn and
      Kramer [Jacobs]; Schwartz-Barcott and Kim; and Rodgers)--are discussed and
      compared in this article. The evolution and modifications of Wilson's method in
      nursing are described and research that has used these methods, assessed. The
      transformation of Wilson's method is traced as each author has adopted his
      techniques and attempted to modify the method to correct for limitations. We
      suggest that these adaptations and modifications ultimately erode Wilson's
      method. Further, the Wilson-derived methods have been overly simplified and used
      by nurse researchers in a prescriptive manner, and the results often do not serve
      the purpose of expanding nursing knowledge. We conclude that, considering the
      significance of concept development for the nursing profession, the development
      of new methods and a means for evaluating conceptual inquiry must be given
      priority.

PMID- 9009819
TI  - The pediatric physiologic stress response: a concept analysis.
AB  - Pediatric nurses have had a long-standing interest in stress and its effect on
      infants and children. Recently, there has been increasing interest in the
      physiological stress response on the part of nurses. While in the pediatric
      critical care setting, nurses continually assess the physiologic stability of the
      critically ill child, as well as the child's responses to a variety of
      interpersonal interactions, clinical interventions, and treatments. This status
      is continually challenged by a multitude of stressors which induce subsequent
      responses by the child. Only through a better understanding of the age
      appropriate physiologic stress response can nurses accurately confirm its
      presence and evaluate its potential consequences. A concept analysis of the
      pediatric physiological stress response was conducted, primarily using the
      strategy recommended by Walker and Avant (1988). Accordingly, this analysis
      included: (1) a literature review; (2) determination of possible uses of the
      concept; (3) selection of defining attributes; (4) identification of empirical
      referents; (5) identification of antecedents and consequences; (6) construction
      of model and alternative cases; and (7) review of implications for nursing
      research.

PMID- 9009820
TI  - Concept development: exploring undocumentedness.
AB  - Concept development involves multiple processes, one of which is concept
      exploration. The purpose of this paper is to present the process of concept
      exploration as exemplified in the case of undocumentedness. This particular
      exploration of undocumentedness was grounded in the discipline of nursing and
      approached from a feminist perspective. The exploratory process of the concept
      included personal reflexivity, the construction of definitions, examination of
      the historical, social, political, and legislative context of undocumented
      immigration in the United States, exploration of the meanings and implications of
      the concept, discussion of the relationship of undocumentedness to nursing and
      health, and identification of the needs for research to further develop the
      concept of undocumentedness for nursing.

PMID- 9009821
TI  - Concept analysis in nursing research: a critical appraisal.
AB  - The four major methodological approaches to concept analysis (Wilson-derived
      methods, qualitative methods, critical analysis of the literature, and
      quantitative methods) are compared. The authors suggest that qualitative methods
      and methods that critically analyze the literature may be selected according to
      the level of the maturity of the concept and the purpose of the analysis. These
      methods have the ability to facilitate inquiry for concept development,
      delineation, comparison, clarification, correction, and identification.
      Quantitative methods may be used for exploring concepts (e.g., delineating
      conceptual boundaries), and quantitative instrumentation may be used for concept
      validation, operationalization, and measurement, thus complementing concept
      analysis methods by moving inquiry into another level of investigation. The
      authors conclude by presenting criteria for the selection of an appropriate
      research approach for concept analysis and criteria for evaluating concept
      analysis research.

PMID- 9009822
TI  - Postpartum fatigue: clarifying a concept.
AB  - This paper describes the multifaceted approach employed to clarify the concept of
      postpartum fatigue. The process began with a literary analysis, which gave rise
      to questions about the defining characteristics of postpartum fatigue and its
      differentiation from related concepts such as tiredness and depression. A series
      of qualitative and quantitative studies were carried out to examine new mothers'
      characterizations of their fatigue, the indicators and predictors of postpartum
      fatigue, and the differences between fatigue and depression. The evolving concept
      clarification suggests that postpartum fatigue is most effectively conceptualized
      as a multidimensional concept with physical and mental aspects that is different
      from tiredness and can be differentiated from postpartal depression or milder
      "baby blues," with which there is some overlap.

PMID- 9009823
TI  - Development of a conceptual model of quality of life.
AB  - Quality of life is a critically important concept for health care that has been
      developed predominantly in the past three decades. Conceptual clarity is
      extremely important, because differences in meaning can lead to profound
      differences in outcomes for research, clinical practice, and allocation of health
      care resources. This paper describes the development of the Ferrans conceptual
      model of quality of life. The model was developed based on the adoption of an
      individualistic ideology, which recognizes that quality of life depends on the
      unique experience of life for each person. Individuals are the only proper judge
      of their quality of life, because people differ in what they value. Consistent
      with this ideology, quality of life was defined in terms of satisfaction with the
      aspects of life that are important to the individual. The model was developed
      using qualitative methodology. Factor analysis of patient data was used to
      cluster related elements into domains of quality of life. The resulting model
      identifies four domains of quality of life: health and functioning,
      psychological/spiritual, social and economic, and family. Subsequent cross
      cultural work with African Americans and Mexican Americans has provided evidence
      that the elements of the model appropriately reflect quality of life for segments
      of the population not sampled in the original work. The Ferrans and Powers
      Quality of Life Index was developed based on this model.

PMID- 9009824
TI  - PDZ domains bind carboxy-terminal sequences of target proteins.

PMID- 9009825
TI  - Kinetic analysis of biosensor data: elementary tests for self-consistency.
AB  - The validity of the most common kinetic interpretation of biosensor data can be
      quickly assessed with the aid of two simple tests for self-consistency, requiring
      only back-of-the-envelope calculations. A search of the recent literature reveals
      that many published results fail these tests qualitatively.

PMID- 9009826
TI  - Tripping the switch fantastic: how a protein kinase cascade can convert graded
      inputs into switch-like outputs.
AB  - Recent experimental work has shown that the mitogen-activated protein (MAP)
      kinase cascade can convert graded inputs into switch-like outputs. The cascade
      could therefore filter out noise (signals of insufficient magnitude or duration)
      and still respond decisively to supra-threshold stimuli. Here, we explore the
      biochemical mechanisms likely to be at the root of this behavior.

PMID- 9009828
TI  - P-type ATPases.

PMID- 9009827
TI  - A likely histone H2A.F/Z variant in Saccharomyces cerevisiae.

PMID- 9009829
TI  - Sphingomyelin breakdown and cell fate.
AB  - A growing number of cell-surface receptors are now being shown to generate
      signals that trigger the hydrolysis of sphingomyelin to release diffusible
      ceramides. Ceramides have been implicated as key mediators in signaling pathways,
      with outcomes as diverse as cell proliferation, differentiation, growth arrest
      and apoptosis. The response depends on cell type, whether the signal is
      integrated with other signals originating from the same receptor and on the
      subcellular location of sphingomyelin hydrolysis and ceramide release.

PMID- 9009830
TI  - Structural insights into the function of the Rab GDI superfamily.
AB  - The 1.81 A crystal structure of Rab GDP-dissociation inhibitor (GDI), a protein
      that plays a critical role in the recycling of Rab GTPases involved in membrane
      vesicular transport, has been recently determined. Biochemical studies implicate
      a highly conserved region involved in Rab binding, which is common to both GDI
      and the evolutionarily-related choroideremia gene product (CHM/REP) required for
      Rab prenylation. Here, we summarize the mechanisms by which members of the GDI
      superfamily might function to coordinate events leading to membrane fusion, and
      we discuss the unexpected, yet striking structural homology of GDI to FAD-binding
      proteins.

PMID- 9009831
TI  - 3'-end-forming signals of yeast mRNA.
AB  - The signals required for forming 3'-ends of mRNAs from the yeast Saccharomyces
      cerevisiae differ from the corresponding signals of higher eukaryotes. Yeast
      signals consist of three elements: (1) the efficiency element, which enhances the
      efficiency of downstream positioning elements; (2) the positioning element, which
      positions the poly(A) site; and (3) the actual poly(A) site. These three elements
      are not only necessary, but also sufficient for mRNA 3'-end formation in yeast.

PMID- 9009832
TI  - Molecular biology and pathogenesis of prion diseases.
AB  - Prions cause a group of human and animal neurodegenerative diseases, which are
      now classified together because their etiology and pathogenesis, involve
      modification of the prion protein (PrP). Prion diseases are manifest as
      infectious, genetic and sporadic disorders. These diseases can be transmitted
      among mammals by the infectious particle designated 'prion'. Despite intensive
      searches over the past three decades, no nucleic acid has been found within
      prions, yet a modified isoform of the host-encoded PrP designated PrPSc is
      essential for infectivity. In fact, considerable experimental data argue that
      prions are composed exclusively of PrPSc. Earlier terms used to describe the
      prion diseases include transmissible encephalopathies, spongiform
      encephalopathies and slow virus diseases. The human prion disorders include kuru,
      Creutzfeldt-Jackob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS)
      and fatal familial insomnia (FFI).

PMID- 9009834
TI  - Methods and reagents. Expression profiling using messenger RNA assays.

PMID- 9009833
TI  - How Ras-related proteins talk to their effectors.
AB  - More and more effectors for the Ras-related protein superfamily are being
      discovered and it is emerging that these GTP-binding proteins interact with more
      than one effector to generate more than one cellular signal. Atomic details for
      the interaction of Rap/Ras with one of the effectors, the protein kinase c-Raf-1,
      have recently become available by X-ray structure analysis. The implications for
      the specificity of the signal transduction pathway, and how the GTP-dependent
      switch mechanism modulates the interaction with effectors will be discussed here,
      using Ras as a paradigm.

PMID- 9009835
TI  - Graphical interface for ProDom domain families.

PMID- 9009836
TI  - A shortcut to interesting human genes: peptide sequence tags, expressed-sequence
      tags and computers.

PMID- 9009837
TI  - Integrating two-dimensional gel databases using the Melanie II software.

PMID- 9009838
TI  - The GDNF-RET signalling partnership.

PMID- 9009839
TI  - Cell-cycle regulation of gene expression by transcriptional repression.

PMID- 9009840
TI  - Cell and genome coevolution: facultative anaerobiosis, glycosomes and
      kinetoplastan RNA editing.

PMID- 9009841
TI  - Browsing DNA cipherspace for sequence variation.

PMID- 9009842
TI  - Decennial tails.

PMID- 9009843
TI  - The world according to hedgehog.
AB  - Members of the Hedgehog family of signaling molecules mediate many important
      short- and long-range patterning processes during invertebrate and vertebrate
      development. In the fly, a single hedgehog gene regulates segmental and imaginal
      disc patterning. In contrast, in vertebrates a hedgehog gene family is involved
      in the control of left-right asymmetry, polarity in the central nervous system
      (CNS), somites and limb, organogenesis, chondrogenesis and spermatogenesis. Here,
      we review recent experiments addressing the function of the various Hedgehog
      members during invertebrate and vertebrate development.

PMID- 9009844
TI  - TRF1, a mammalian telomeric protein.
AB  - Telomerase adds TTAGGG repeats onto mammalian chromosome ends, replenishing the
      terminal sequence loss incurred during DNA replication. This maintenance of
      telomeric DNA preserves binding sites for telomeric proteins, which form a
      protective nucleoprotein complex at chromosome ends. The recent isolation of
      TRF1, the mammalian telomeric-repeat binding factor, should now allow the
      structure and function of the telomeric complex to be examined in detail.

PMID- 9009845
TI  - The molecular epidemiology of p53 gene mutations in human breast cancer.
AB  - The P53 tumor-suppressor gene is an advantageous tool for analyzing the molecular
      epidemiology of cancer. We describe the utility of the P53 gene as a 'mutagen
      test' and a prognostic indicator in breast cancer. Aspects of study design and
      methodology are discussed. Two major conclusions emerge: (1) there is an
      extraordinary diversity of mutational patterns among cohorts, hinting that the
      unique biology of mammary cells results in exposure to high doses of a diversity
      of ingested lipophilic mutagens; and (2) mutations in the P53 gene predict poor
      outcome in breast cancer.

PMID- 9009847
TI  - Internet resources for the parasite genome projects.

PMID- 9009846
TI  - Neuroblasts: a model for the asymmetric division of stem cells.
AB  - The ability of stem cells to self-renew has hung been attributed to an asymmetry
      in division that generates one daughter cell identical to the mother and another
      cell committed to differentiation. Recent studies on neuroblasts, a group of
      neural stem cells responsible for generating various neurons and glial cells in
      the central nervous system, have revealed exciting mechanisms that underlie self
      renewing asymmetric division. Several important localized cell fate determinants
      have been characterized, and their segregation mechanism has been explored in the
      context of cytoskeletal organization, cell-cycle type progression, cytokinesis
      and mitotic orientation. These findings are illuminating in understanding the
      general mechanism of stem cell division.

PMID- 9009848
TI  - Is there a need to require mandatory continuing medical education?

PMID- 9009853
TI  - 50th annual J. Shelton Horsley Lecture. Gains and losses in the modern diagnosis
      of abdominal pain.

PMID- 9009849
TI  - Medical device reporting regulations.

PMID- 9009854
TI  - Urokinase thrombolysis as initial therapy for acute and non-acute ischemic
      extremities.
AB  - Limb ischemia, both acute and chronic, presents a risk to life and limb with
      mortality rates from 3% to 37% and amputation rates of the same range. Our
      experience with urokinase thrombolysis as the initial therapy for acute and non
      acute ischemic extremities over 57 consecutive cases of native arterial occlusion
      by either thrombus or embolus has resulted in no mortality and only 3.5%
      requiring amputation (2 of 57). In 74% of cases initial thrombolytic therapy was
      followed by either balloon angioplasty (35 patients) or surgery (7 patients) to
      relieve the underlying cause of obstruction (i.e., stenosis, occlusion or
      aneurysm). Thrombolysis alone was sufficient and effective treatment in the
      remaining 26% (15 patients).

PMID- 9009855
TI  - Latex allergy.
AB  - Latex is a natural product obtained from rubber trees. Sensitization and
      subsequent exposure to latex products can lead to allergic (immediate
      hypersensitivity) reactions including anaphylaxis. Gloves are the largest source
      of latex exposure, and the majority of serious latex reactions occur in medical
      settings. Allergen testing and avoidance in history positive or high risk groups
      (medical personnel, spina bifida patients and rubber workers) is presently the
      best treatment option.

PMID- 9009857
TI  - CHD and GPV technical briefings at WHO headquarters.

PMID- 9009856
TI  - Revision of the International Health Regulations. Progress report, December 1996.

PMID- 9009858
TI  - Food safety. Outbreak of Escherichia coli O157 infection.

PMID- 9009860
TI  - The relationship of menopausal status and serum ferritin to cardiovascular risk.

PMID- 9009861
TI  - Women's attitudes toward breast cancer screening procedures: differences by
      ethnicity.

PMID- 9009862
TI  - Unintended pregnancy and the psychosocial well-being of pregnant women.

PMID- 9009863
TI  - A comparison of a mind/body approach versus a conventional approach to aerobic
      dance.

PMID- 9009864
TI  - Older women and physical activity: using the telephone to walk.

PMID- 9009865
TI  - The benefits of physical activity on coronary heart disease and coronary heart
      disease risk factors in women.

PMID- 9009866
TI  - Physical activity and exercise: a first step to health promotion and disease
      prevention in women of all ages.

PMID- 9009867
TI  - Physical activity and psychological well-being in older women.

PMID- 9009868
TI  - Physical activity and exercise among women.

PMID- 9009870
TI  - Outpatient treatment of dyslexia through stimulation of the cerebral hemispheres.
AB  - Although a number of experimental investigations into the effects of hemisphere
      stimulation on the reading performance of individuals with dyslexia are currently
      available, only a few studies have addressed the effects of treatment in the
      setting of an outpatient clinic. The present study reports on the reading results
      after a treatment that was based on the balance model and incorporated notions
      from cognitive psychological origin in 80 children with severe dyslexia who were
      referred to the outpatient clinic of the Paedological Institute in Amsterdam.
      Treatment was individually tailored, depending on the type of dyslexia, the phase
      of the learning-to-read process, and the intermediate results of treatment.
      Effects on reading performance, measured after preclinical (home-training),
      clinical, and postclinical intervention periods, were analyzed through multiple
      time-series and multilevel analyses. Treatment with flash cards, exercising
      automatic letter-sound conversions, appeared to have a robust and slight effect
      in the preclinical and clinical phases, respectively, whereas hemisphere
      stimulation produced robust effects in both the clinical and the postclinical
      period. The results are discussed in terms of theoretical models, experimental
      findings of other investigations, intellectual and scholastic characteristics of
      the subjects, and such treatment factors as compliance (see Note).

PMID- 9009871
TI  - The legacy of Jan Kappers.

PMID- 9009872
TI  - Foreign language proficiency of at-risk and not-at-risk learners over 2 years of
      foreign language instruction: a follow-up study.
AB  - In this follow-up study, students at risk for problems with learning a foreign
      language who were taught using a multisensory, structured language approach to
      Spanish made significant gains over 2 years on three native language
      phonological/orthographic measures and a foreign language aptitude test. Despite
      gains, at-risk students did not "catch up" with not-at-risk students on these
      measures. Qualitative between-group differences were noted on foreign language
      proficiency measures.

PMID- 9009873
TI  - The effects of goal setting and self-instruction on learning a reading
      comprehension strategy: a study of students with learning disabilities.
AB  - This study examined the contributions of instruction in goal setting and self
      instruction, separately and combined, on the acquisition, maintenance, and
      generalization of a reading comprehension strategy by fourth-through sixth-grade
      students with learning disabilities. A previously validated strategy involving
      the use of story structure to analyze and remember story content was taught to 47
      students with learning disabilities using the self-regulated strategy development
      (SRSD) model. Comparisons were made among students with learning disabilities in
      four conditions (strategy instruction, strategy instruction plus goal setting,
      strategy instruction plus self-instruction, and strategy instruction plus goal
      setting and self-instruction). Result indicated that instruction in the reading
      strategy produced meaningful, lasting, and generalizable effects on students'
      story comprehension skills. Furthermore, the comprehension performance of the
      students with learning disabilities after strategy instruction was
      indistinguishable from that of a social comparison group of normally achieving
      students. Explicit instruction in goal setting and self-instruction, however, did
      not augment the comprehension performance of students with learning disabilities.

PMID- 9009874
TI  - Teacher response to learning disability: a test of attributional principles.
AB  - Attribution research has identified student ability and effort expended as causes
      of achievement outcomes that result in differing teacher affect, evaluative
      feedback, and expectation of future performance. Ninety-seven elementary-school
      general education teachers (84 women and 13 men) rated their responses to the
      test failures of hypothetical boys with and without learning disabilities. In
      most cases, greater reward and less punishment, less anger and more pity, and
      higher expectations of future failure followed the negative outcomes of the boys
      with learning disabilities, when compared with their nondisabled ability and
      effort matches, indicating that learning disability acts as a cause of
      achievement outcomes in the same way as ability and effort. This pattern of
      teacher affect and response can send negative messages that are often interpreted
      as low-ability cues, thus affecting students' self-esteem, sense of competence as
      learners, and motivation to achieve.

PMID- 9009875
TI  - Educational assessment of mathematics skills and abilities.
AB  - Mathematics assessments play a valuable role in identifying students' strengths
      and weaknesses and in developing and monitoring instructional practice. Over the
      last century, mathematics assessment has been refined as math content has changed
      as a result of curriculum reform. Today, researchers and practitioners use
      various assessment techniques to (a) identify students who have mathematics
      learning disabilities (LD), (b) target individual strengths and weaknesses across
      mathematics areas, (c) document the effects of mathematics instruction in a
      remedial or special program, (d) identify strategies that students employ during
      math activities, (e) conduct research about the characteristics of students with
      math LD, and (f) examine the technical characteristics of mathematics tests. This
      article provides an historical overview of the development of mathematics
      assessment and a description of specific strategies for conducting math
      evaluations.

PMID- 9009876
TI  - Educational aspects of mathematics disabilities.
AB  - Research suggests that students with learning disabilities have significant
      difficulty acquiring and retaining math skills. A variety of factors seem to be
      contributing to the poor math performance of these individuals. The purpose of
      this article is to discuss these factors and make recommendations that will
      enhance the likelihood of better math performance. The article begins with a
      discussion of national reform movements that have influenced math instruction
      (i.e., National Council of Teachers of Mathematics Standards, minimum competency
      testing, graduation requirements, inclusion). Next, learner characteristics are
      reviewed, then issues related to math instruction are described. Finally, ways to
      improve current practices in math education are discussed.

PMID- 9009877
TI  - Disabilities of arithmetic and mathematical reasoning: perspectives from
      neurology and neuropsychology.
AB  - Current research on brain-behavior relationships in disabilities of arithmetic
      and mathematical reasoning is reviewed from both a neurological and a
      neuropsychological perspective. Although no entirely satisfactory statement of
      the relationship between arithmetic skills and brain functions has yet emerged,
      investigators in this area have provided evidence regarding the involvement of
      some brain systems in processes of calculation. Also, the developmental
      importance of right- versus left-hemisphere integrity for the mediation of
      arithmetic learning and performance has been suggested. We propose that an
      account of brain-behavior relationships in children intended to explain and
      predict developmental disabilities of arithmetic learning needs to address
      several important content and processing distinctions in order to (a) encompass
      empirically derived subtypes of children with learning disabilities who exhibit
      difficulties with arithmetic and (b) provide adequate direction for future
      subtyping and intervention research.

PMID- 9009878
TI  - Mathematics learning disabilities: a view from developmental psychology.
AB  - U.S. education suffers from shortcomings that put even children possessing
      adequate intellectual abilities at risk for low mathematics achievements.
      Consequently, identifying and understanding children whose academic failure is
      influenced by a genuine learning disability requires a complex "developmental"
      research agenda. This perspective suggests the use of sensitive research methods-
      clinical interviews, ethnographies--to examine the development of children's
      construction of knowledge in the context of schooling. Researchers should
      consider such factors as the adequacy of classroom instruction, the availability
      in children of informal knowledge, the role of motivation, the effects of
      specific interventions, the role and operation of different cognitive processes
      in constructing mathematical understanding, children's difficulties across
      different areas of mathematics, and the development of children's thinking
      throughout the school years.

PMID- 9009879
TI  - Mathematics education and students with learning disabilities: introduction to
      the special series.
AB  - The prevalence of students with mathematics learning disabilities has triggered
      an interest among special education researchers and practitioners in developing
      an understanding of the needs of this group of students, and in identifying
      effective instructional programming to foster their mathematical performance
      during the school years and into adulthood. Research into the characteristics of
      students with mathematics learning disabilities is being approached from
      different perspectives, including developmental, neurological and
      neuropsychological, and educational. This diversity helps us develop a broader
      understanding of students' learning needs and difficulties. Special education
      assessment practices encompass a variety of approaches, including norm
      referenced, criterion-referenced, and nonstandardized procedures, depending on
      the specific assessment questions professionals seek to answer. Students'
      mathematical knowledge and conceptual understanding must be examined to determine
      their strengths and weaknesses, curriculum-based progress, and use of cognitive
      strategies to arrive at mathematical solutions. Research findings have identified
      empirically validated interventions for teaching mathematics curricula to
      students with mathematics learning disabilities. Research studies have been
      grounded in behavioral theory and cognitive psychology, with an emergent interest
      in the constructivist approach. Although research studies have focused primarily
      on computational performance, more work is being conducted in the areas of story
      problem solving and technology. These areas as well as other math curricular
      skills require further study. Additionally, the needs of adults with math LD have
      spurred educators to examine the elementary and secondary math curricula and
      determine ways to infuse them with life skills instruction accordingly. As the
      field of mathematics special education continues to evolve, special educators
      must remain cognizant of the developments in and influences on the field of
      mathematics education. Reform efforts have shaped the field significantly since
      the 1950s, contributing to the curriculum offered in mathematics textbooks and
      the pedagogical practices taught in higher education courses. Mathematics
      educators continue to search for a better understanding of how children learn
      mathematics; this process is shaped by the prevailing theoretical orientations
      and research methodologies. This special series in mathematics special education
      provides readers with information about the characteristics of students with
      mathematics learning disabilities, assessment procedures, mathematics
      programming, teacher preparation, and future directions for the field. The series
      originated as a result of discussions with Dr. Lee Wiederholt and Dr. Judith K.
      Voress, who saw a need for the compilation of recent research and best practices
      in mathematics special education. I thank them for their support of and
      thoughtful insights about the development of this series. I also appreciate the
      support of Dr. George Hynd and his editorial assistant, Kathryn Black, in
      finalizing the details for publication. Finally, I am most appreciative of the
      authors' contributions to this series; their work continues to significantly
      influence the development of the field of mathematics special education and
      programming for students with mathematics learning disabilities.

PMID- 9009880
TI  - A computational theory of executive cognitive processes and multiple-task
      performance: Part 1. Basic mechanisms.
AB  - A new theoretical framework, executive-process interactive control (EPIC), is
      introduced for characterizing human performance of concurrent perceptual-motor
      and cognitive tasks. On the basis of EPIC, computational models may be formulated
      to simulate multiple-task performance under a variety of circumstances. These
      models account well for reaction-time data from representative situations such as
      the psychological refractory-period procedure. EPIC's goodness of fit supports
      several key conclusions: (a) At a cognitive level, people can apply distinct sets
      of production rules simultaneously for executing the procedures of multiple
      tasks; (b) people's capacity to process information at "peripheral" perceptual
      motor levels is limited; (c) to cope with such limits and to satisfy task
      priorities, flexible scheduling strategies are used; and (d) these strategies are
      mediated by executive cognitive processes that coordinate concurrent tasks
      adaptively.

PMID- 9009881
TI  - Visual marking: prioritizing selection for new objects by top-down attentional
      inhibition of old objects.
AB  - The authors propose a new mechanism for prioritizing the selection of new events:
      visual marking. In a modified conjunction search task the authors presented one
      set of distractors before the remaining items, which contained the target if
      present. Search was as efficient as if only the second items were presented. This
      held when eye movements were prevented and required a gap of 400 ms between the
      old and new items. The effect was abolished by luminance changes at old
      distractor locations when the new items appeared, and it was reduced by the
      addition of an attention demanding load task. The authors propose that old items
      can be ignored by spatially parallel, top-down attentional inhibition applied to
      the locations of static stimuli. The authors discuss the relations between
      marking and other accounts of visual selection and potential neurophysiological
      mechanisms.

PMID- 9009883
TI  - Processes of memory loss, recovery, and distortion.
AB  - The author proposes that many forms of memory distortion, including the
      progressive changes in recollection of a learning experience often observed over
      successive tests, are due to the same processes that yield veridical recollection
      in some circumstances and memory loss and recovery in others. In a framework for
      interpreting all of these aspects of memory, the author assumes that the objects
      and events of a learning experience are encoded in parallel in traces of their
      perceptual attributes, which are basic to recognition, and in traces of reactions
      made to the events during or following learning, which are basic to recall.
      Random perturbation of remembered attribute values in both types of traces over
      retention intervals is a pervasive cause of both loss and distortions of memory.

PMID- 9009882
TI  - Language production and serial order: a functional analysis and a model.
AB  - In speech production, previously spoken and upcoming words can impinge on the
      word currently being said, resulting in perseverations (e.g., "beef needle soup")
      and anticipations (e.g., "cuff of coffee"). These errors reveal the extent to
      which the language-production system is focused on the past, the present, and the
      future and therefore are informative about how the system deals with serial
      order. This article offers a functional analysis of serial order in language and
      develops a general formal model. The centerpiece of the model is a prediction
      that the fraction of serial-order errors that are anticipatory, as opposed to
      perseveratory, can be closely predicted by overall error rate. The lower the
      error rate, the more anticipatory the errors are, regardless of the factors
      influencing error rate. The model is successfully applied to experimental and
      natural error data dealing with the effects of practice, speech rate, individual
      differences, age, and brain damage.

PMID- 9009884
TI  - Biological consequences of drug administration: implications for acute and
      chronic tolerance.
AB  - The authors presented a model that extrapolates the biological consequences of
      drug administration to account for acute and chronic tolerance. Drug-induced
      changes of regulated parameters provide detectable perturbations to which the
      brain responds. With experience, these centrally mediated responses are learned
      and can be activated in the absence of the drug-induced perturbation. Although
      neural responses following drug administration are often obscured, the model
      shows how these responses may be identified and provides a reinterpretation of
      drug conditioning paradigms. The authors made comparisons between the present
      empirical model of drug administration and existing theories of drug tolerance.
      The authors also presented a unified framework for understanding the consequences
      of repeated drug use and made specific predictions as to the relationships among
      acute and chronic tolerance, drug sensitization, and individual differences in
      vulnerability to drug addiction.

PMID- 9009885
TI  - Outcomes of mandated preventive services programs for homeless and truant
      children: a follow-up study.
AB  - This study examined factors predicting favorable outcomes for families
      participating in mandated preventive services (MPS) programs, which included a
      truancy diversion program and a program for adolescents from homeless families.
      Case records of 100 families referred out of the program between 1989 and 1994
      were reviewed to ascertain social workers' ratings of five factors predicting
      successful outcomes. Criterion measures included compliance with the termination
      plan and ratings of the child's adjustment six months after MPS termination.
      Results indicated that the criterion measures were related significantly to four
      predictive factors: severity of the child's pathology, intensity of parental
      involvement in treatment, parental attendance, and parental understanding of the
      child's pathology.

PMID- 9009886
TI  - Homeless veterans: perspectives on social services use.
AB  - This study analyzes the nature and scope of homelessness and issues related to
      social services use. Using focus group interviews, this exploratory study
      examined the expressed needs of homeless veterans and the obstacles encountered
      in obtaining health and human services. Types of problems and social services
      barriers were developed with exemplars from the interviews. These veterans self
      reported a high incidence of health and mental health problems, limited
      resources, negative public perceptions and treatment, insensitive service
      providers, dehumanizing policies and procedures, and high levels of stress and
      frustration with the service delivery system. They encountered personal,
      situational, and bureaucratic barriers to obtaining services and were highly
      critical of service providers. These findings suggest a need for greater emphasis
      on advocacy-based case management services, affordable housing, employment
      opportunities, increased sensitivity in service delivery systems, and empowerment
      centered practice.

PMID- 9009887
TI  - Housing distress among high school students.
AB  - The word "homelessness" is not a useful term to explain housing problems
      experienced by high school-aged youths. The term "housing distress" is preferable
      because it includes both teenagers who are homeless and those who are at risk of
      homelessness. Many teenagers feel that they have no place where they belong and
      seek alternative living arrangements for a variety of reasons. Housing distress
      is a problem for schools because students have difficulties achieving academic
      success when they have no consistent, safe place to live. To understand how much
      or how little housing distress is experienced by high school-aged youths, 3,676
      high school-aged teenagers were surveyed in nine communities along the seacoast
      of New Hampshire and southwestern Maine. Between 5 percent and 10 percent of the
      teenagers surveyed reported that they had been homeless sometime during the past
      year. Up to 20 percent of the high school students lived in arrangements that
      could be considered to be distressing and to put them at risk of becoming
      homeless.

PMID- 9009888
TI  - Perceptions of school violence as a problem and reports of violent events: a
      national survey of school social workers.
AB  - Awareness of violence as a problem is important in developing school-based
      interventions to reduce violence. How would social workers who reported a
      potentially lethal event in their schools within the past year rate the
      seriousness of the problem in their schools? What variables would be associated
      with the perception of a serious violence problem in a school? These questions
      were explored in a national survey of school social workers. The results suggest
      that school social workers did not perceive violence as a serious problem on the
      basis of a single event even when the event was life threatening. From a zero
      tolerance perspective, school violence as a problem was underestimated in all
      community settings but more often in suburban and rural settings than in inner
      city or urban settings. The social workers' perception of a serious problem was
      contingent on the presence of multiple types of violence and the community
      setting of the school.

PMID- 9009889
TI  - Unilateral interventions for women living with heavy drinkers.
AB  - Despite the fact that unilateral therapy is often the only treatment option for
      women living with heavy drinkers, very few structured programs have been
      developed for this client group. Moreover, the programs that do exist lack
      empirical support (as in the case of Al-Anon) or have as their highest priority
      promoting change in the drinker. This article looks at unilateral therapy for
      women partners of heavy drinkers and concludes that although a number of
      promising developments have occurred in recent years, more research is needed on
      the benefits to the women themselves.

PMID- 9009890
TI  - Mental retardation and domestic violence: an ecological approach to intervention.
AB  - The public and health and law enforcement professionals have finally become aware
      of the problem of domestic violence among community-dwelling women with
      developmental disabilities such as mental retardation. This article presents an
      ecological approach to analyzing factors that contribute to and maintain such
      abuse. Service needs of women with developmental disabilities who experience
      domestic violence as well as assumptions that should underlie treatment are
      addressed within an ecological framework. Assessment and individual and group
      intervention are discussed, including the development of a personal safety plan.
      A case example is provided.

PMID- 9009891
TI  - Pseudoissues in practice evaluation: impediments to responsible practice.
AB  - This article reviews often-cited barriers to the implementation of practice
      evaluation activities and suggests that they are pseudoissues. Five pseudoissues
      in evaluation are reviewed: (1) time constraints, (2) single-system design
      issues, (3) gender and ethnic bias, (4) complexity of practice, and (5)
      incompatibility between the science of evaluation and the art of helping. These
      pseudoissues result from two misconceptions: First, these issues are sometimes
      viewed as affecting only the evaluation component of practice, but they pervade
      all of practice. Second, the confusion about the purpose of single-system designs
      leads to unwarranted concerns about design and methodology. The article argues
      that the incorporation of evaluation activities in practice helps practitioners
      become more aware of and sensitive to legitimate barriers to effective practice
      and paves the way for overcoming these barriers.

PMID- 9009892
TI  - Using a focus group of clinicians to develop a research project on therapeutic
      process for clients with dual diagnoses.

PMID- 9009893
TI  - Taking exception to "Asymmetrical role-taking: comparing battered and nonbattered
      women".

PMID- 9009894
TI  - Domestic violence and role-taking: collegial inaccuracies.

PMID- 9009895
TI  - Challenging the conventional wisdom.

PMID- 9009896
TI  - Know your antidiabetic agents.

PMID- 9009897
TI  - Patient restraints: no way out.

PMID- 9009898
TI  - Hospital horrors.

PMID- 9009899
TI  - Using local anesthetics to control procedural pain.

PMID- 9009900
TI  - Reducing the pain of lidocaine.

PMID- 9009901
TI  - Treating acute alcohol withdrawal.

PMID- 9009902
TI  - Elder abuse: what to look for, how to intervene.

PMID- 9009903
TI  - Clinical snapshot: Raynaud's syndrome.

PMID- 9009904
TI  - Developing a nursing ethics roundtable.

PMID- 9009905
TI  - Managing asthma: it takes teamwork.

PMID- 9009907
TI  - Emergency! Paroxysmal supraventricular tachycardia.

PMID- 9009906
TI  - Update on HIV infection.

PMID- 9009908
TI  - 'I'm a registered nurse'.

PMID- 9009909
TI  - Community nursing organizations: a new frontier.

PMID- 9009910
TI  - Is health care regulation really dead?

PMID- 9009912
TI  - Books of the year.

PMID- 9009913
TI  - Document helps school nurses deal with HIV/AIDS.

PMID- 9009911
TI  - New mother at risk.

PMID- 9009914
TI  - Nurses: a 'capital gang' to be reckoned with.

PMID- 9009915
TI  - Comment on concentration and etching time of phosphoric acid.

PMID- 9009916
TI  - Bonded magnets used in the treatment of anterior open bite. Reply to Dr.
      Dellinger (previously printed in the September 1996 issue)

PMID- 9009917
TI  - Force decay and deformation of orthodontic elastomeric ligatures.
AB  - This study evaluated commercially available molded gray elastomeric ligatures
      from seven companies for force decay, dimensional change, and the relationship
      between ligature dimension and force. The initial wall thickness, inside
      diameter, outside diameter, and force levels of each ligature were measured.
      Three of four test groups of ligatures were stretched over stainless steel dowels
      with a circumference approximating that of a large orthodontic twin bracket. Test
      group 1 was kept at room temperature and humidity for 28 days and test group 2 in
      a synthetic saliva bath at 37 degrees C, pH 6.84 for 28 days. The residual forces
      and dimensional changes were measured. The third test group was placed in a
      synthetic saliva bath at 37 degrees C, pH 6.84, and force levels recorded at
      initial, 24 hours, 7 days, 14 days, and 28 days. The fourth test group of
      unstretched samples was placed in a synthetic saliva bath at 37 degrees C, pH
      6.84 for 28 days to evaluate dimensional changes due solely to moisture sorption.
      The results for stretched samples in a simulated oral environment revealed the
      following: (1) Moisture and heat had a pronounced effect on force decay and
      permanent deformation, (2) a positive correlation existed between the wall
      thickness and force, (3) a negative correlation existed between the inside
      diameter and force, (4) a weak correlation existed between outside diameter and
      force, (5) the greatest force loss occurred in the first 24 hours and the decay
      pattern was similar for all ligatures tested, and (6) unstretched ligatures
      absorbed moisture in the range of 0.060% to 3.15%. The ligatures tested appear to
      be suitable for use during initial aligning and leveling. However, the rapid
      force loss and permanent deformation of these products may preclude their use for
      rotational and torque corrections.

PMID- 9009918
TI  - A role of pharyngeal length in obstructive sleep apnea patients.
AB  - A narrow pharyngeal pathway may be one of the most significant predisposing
      factors for obstructive sleep apnea (OSA). Accordingly, the objectives of many
      treatment modalities are focused on widening the constricted part of the pharynx.
      Despite the obvious limitations as a two-dimensional imaging technique,
      cephalometrics has been used more recently as a clinical screening tool for OSA.
      This study was designed to investigate whether pharyngeal variables more reliable
      than a single measurement of the most constricted area exist in cephalograms. A
      total of 80 pairs of upright and supine cephalograms were obtained and
      subclassified into four groups, in accordance with OSA severity. A medial axis
      program conveniently provided the variables for the study by transforming
      digitized outlines of the pharyngeal structure. The results indicate that the
      pharyngeal length and the pharyngeal width below the most constricted area may be
      the most important variables. We observed that the pharynx becomes considerably
      longer in the apneic group after a body position change from upright to supine.
      Pharyngeal length in the supine position may be more important than a one
      dimensional measurement of the most constricted area in the diagnosis and
      treatment of OSA.

PMID- 9009919
TI  - Treatment and posttreatment changes in patients with Class II, Division 1
      malocclusion after extraction and nonextraction treatment.
AB  - The purpose of this study was to evaluate the treatment and posttreatment changes
      in the facial and dental parameters in two groups of patients with Class II,
      Division 1 malocclusions. In one group (n = 46), the patients were treated with a
      nonextraction approach, whereas in the second group (n = 45), the treatment
      included the extraction of four first premolars. The treatment groups were
      compared with matched untreated normals (n = 35) from the Iowa Growth Study.
      Lateral cephalograms and dental casts were evaluated at three stages:
      pretreatment, posttreatment, and approximately 2 years after treatment. Student's
      t tests were used to compare the extraction and nonextraction groups.
      Significance was predetermined at p < or = 0.05. The cephalometric findings
      indicate that before treatment, the subjects treated with four first premolar
      extractions had more protrusive upper and lower lips and a larger tooth size-arch
      length discrepancy. After treatment the upper and lower lips were more retrusive
      in the extraction groups, and more protrusive in the nonextraction groups. The
      extraction groups tended to have straighter faces and slightly more upright
      maxillary and mandibular incisors, whereas the nonextraction groups had the
      opposite tendencies. The average soft tissue and skeletal measurements for both
      groups were close to, but on opposite sides of, the corresponding averages
      derived from the Iowa normative standards. The findings from the dental arch
      measurements indicate that after treatment both the extraction and nonextraction
      groups experienced an increase in tooth size-arch length discrepancy and a
      reduction in arch length. In general, extractions did not significantly alter the
      direction of the overall posttreatment trends. Furthermore, the trends in the
      posttreatment changes were similar in male and female patients, as well as in the
      maxillary and mandibular arches. The current findings suggest that the
      extraction/nonextraction decision, if based on sound diagnostic criteria, does
      not have a systematic detrimental effect on the facial profile. But clinicians
      should be aware of the trends introduced by the two treatment modalities to avoid
      accentuating undesirable profile characteristics.

PMID- 9009920
TI  - Cleidocranial dysplasia: Part 1--General principles of the orthodontic and
      surgical treatment modality.
AB  - Over several decades, occasional reports of dental treatment provided by an
      individual practitioner to patients suffering with cleidocranial dysplasia have
      appeared in the literature. In the past, the main treatment was prosthetic
      replacement. Orthodontic treatment has only recently been considered as a serious
      treatment option, with success being described in several aspects of this
      treatment modality, in published individual case reports. Given the rarity of the
      condition, guidelines for the treatment of cleidocranial dysplasia are difficult
      to find in the literature, because few practitioners have treated enough cases to
      be in a position to make such recommendations. Two different approaches have been
      proposed in the past and are discussed here. The relative advantages of a third
      approach are expounded in detail.

PMID- 9009921
TI  - An evaluation of condyle position in centric relation obtained by manipulation of
      the mandible with and without leaf gauge deprogramming.
AB  - Centric relation records of 19 dental students were obtained with leaf gauges and
      by mandibular manipulation. The condyle/fossa relationships were subsequently
      evaluated with enhanced sagittal cephalometry. Both clinical methods of obtaining
      centric relation revealed considerable variation of the condyle location within
      the glenoid fossa. Only 10% of the patients showed a condyle position "upward and
      forward" in the fossa with the leaf gauge method. In the mandibular manipulation
      technique of obtaining centric relation, 10% of the patients showed an "upward
      and rearward" position of the condyle.

PMID- 9009922
TI  - Influences of nasal respiratory obstruction on craniofacial growth in young
      Macaca fuscata monkeys.
AB  - This study was conducted to investigate the influences of artificial nasal
      respiratory obstruction on craniofacial growth in young Macaca fuscata monkeys.
      Eleven monkeys were used; seven monkeys served as the experimental animals and
      the remaining four as the control animals. Further, the experimental animals were
      divided into light and heavy obstruction groups. Nasal respiratory obstruction
      was created by injecting dental impression material into the nasopharyngeal
      region. Nasal respiratory function was evaluated in terms of nasal airway
      resistance. Craniofacial structure in the experimental monkeys was compared with
      the control animals by means of cephalometric analysis. Nasopharyngeal
      respiratory obstruction was associated with downward and backward rotation of the
      mandible, upward and backward growth of the condyle, divergent gonial angle,
      anterior open bite, and spaced dental arch in the lower anterior region. These
      changes were significantly greater in the experimental monkeys with heavy
      respiratory obstruction. The current findings support the hypothesis that nasal
      obstruction existing before and during pubertal growth may result in permanent
      craniofacial deformities pertinent to skeletal open bite.

PMID- 9009923
TI  - Heritability of 39 orthodontic cephalometric parameters on MZ, DZ twins and MN
      paired singletons.
AB  - The twin method is one of the most effective methods available for investigating
      genetically determined variables in orthodontics, as well as in other medical
      fields, depending on the variance in the shape and the size of skull and teeth,
      both on genetic and environmental influences. The former have been extensively
      evaluated and, in particular, most of the facial and dental cephalometric
      parameters have shown high heritability, the vertical parameters have a higher
      genetic control compared with the horizontal ones. Nevertheless, most of the
      results provided by twin research have been considered arbitrary if directly
      transferred to a singleton population and in further studies, including extensive
      analysis of the parents, familial and nutritional habits have been recommended.
      In this study, heritability of 39 lateral orthodontic cephalometric parameters
      has been estimated by both statistical method of path analysis and Dahlberg'
      quotient in three orthodontic samples of young monozygotic and dizygotic twins
      and same-sex pairs of singletons living together, matched for sex and age, to
      evaluate genetic versus environmental factors affecting heritability of
      craniofacial features in the aim to obtain results not only statistically
      significant but also transferrable to a singleton population. Different
      inheritance trends, showing the highest concordance of values between monozygotic
      twin pairs when compared with dizygotic twin pairs or the same-sex singletons
      paired group, come from the 39 selected lateral cephalometric parameters,
      confirming the hypothesis that strong genetic control is exerted especially on
      the vertical ones. Heritability seems to have more influence on anterior vertical
      parameters than posterior. Mandibular structure seems to be more genetically
      determined than mandibular size. All five Ricketts' cephalometric typological
      parameters confirm high heritability coefficients, the same applies to the linear
      horizontal McNamara's measurement and lower incisor to A-Pg line. The two tested
      statistical methods showed relevant concordance of results.

PMID- 9009924
TI  - The effects of lip bumper therapy in the mixed dentition.
AB  - A prospective clinical trial was undertaken to study the effects of 6 months of
      continuous lip bumper therapy on patients in the mixed dentition with mild-to
      moderate mandibular arch perimeter deficiency. Thirty-four patients, ages 7.9 to
      13.1 years (mean = 10.2), seeking treatment in the postgraduate orthodontic
      clinic of the Medical College of Virginia, presented possessing 3 to 8 mm of
      mandibular crowding, with both mandibular primary second molars, were randomly
      placed in either the treatment or nontreatment group. Treated subjects underwent
      continuous lip bumper therapy, whereas the control subjects were monitored
      without undergoing any active treatment, each for 6 months. Arch dimension
      changes were assessed with study models. Alterations of mandibular incisor
      position were measured from lateral cephalometric radiographs. Mandibular left
      permanent first molar position changes were determined from both lateral
      cephalometric and tomographic radiographs, with the resolution of each imaging
      technique in measuring molar tooth movement also compared. It was found that
      significant differences in mandibular incisor inclination, molar position, arch
      length, and arch perimeter existed between treated and untreated subjects. In
      addition, multiple observer analysis showed that cephalometric examination lacks
      sensitivity when used to measure molar movement.

PMID- 9009925
TI  - Changes in dental arch dimensions by use of an orthopedic cervical headgear in
      Class II correction.
AB  - Orthopedic cervical headgears are commonly used in Finland for early treatment of
      the Class II malocclusion, but there is a lack of follow-up studies on the effect
      of this treatment. We have evaluated the effects of the cervical headgear therapy
      with an expanded inner bow to treat Class II malocclusion and dental arches.
      Forty children, 20 boys and 20 girls, with Class II, Division 1 malocclusion,
      were treated with the orthopedic cervical headgear. No other appliances were
      used. The mean age of the subjects in the beginning of the treatment was 9.3 +/-
      1.3 years (range 6.6 to 12.4 years). The mean treatment time was 1.8 +/- 0.6
      years (range 0.8 to 3.1 years). The cervical headgear was used with a 10 mm
      expanded inner bow and a 15 degrees upward bend of the long outer bow, 12 to 14
      hours a day with a force of 500 gm per side. Class I relationships were achieved
      in all subjects. At the same time, the maxillary and mandibular dental arches
      were widened. The annual increment in the intercanine and intermolar distances
      was significantly greater than in healthy control subjects (literature data),
      except for the mandibular intercanine distance in boys. The maxillary arch
      lengths were also significantly increased; there were no consistent changes of
      the mandibular arch lengths. Class II malocclusion may be treated with the
      orthopedic cervical headgear. The treatment results in increased growth of the
      dental arch widths by expansion of the inner bow of the headgear. The widening of
      the maxilla is followed by spontaneous widening of the mandible.

PMID- 9009926
TI  - Bonded orthodontic retainers: the wire-composite interface.
AB  - The bonded orthodontic retainer constructed from multistrand wire and composite
      is an efficient esthetic retainer, which can be maintained long-term. Clinical
      failures of bonded orthodontic retainers, most commonly at the wire/composite
      interface, have been reported. This in vitro investigation aimed to evaluate
      selected multistrand wires and composite materials that are available for use in
      the construction of bonded fixed retainers. An in vitro model was developed to
      simulate the forces encountered at the wire/composite interface. No significant
      difference was detected between different multistrand wire types and diameters
      with regard to retention in composite. Wires were placed in one of three groups
      according to surface characteristics identified with scanning electron
      microscopy. Increasing the thickness of composite overlying the wire increased
      the force required to detach the wire from the composite. Thickness of composite
      greater than 1.0 mm overlying the wire may give little clinical advantage.
      Greater force was required to detach the wire from Concise Orthodontic (3M
      Unitek) than any other composite tested. In vitro abrasion resistance testing
      found Heliosit Orthodontic (Vivadent) and Right On (TP Orthodontics, Inc.) to
      have poor abrasion resistance, whereas Concise Orthodontic and Transbond (3M
      Unitek) had abrasion resistance comparable with restorative composites. Clinical
      recommendations are made based on these findings.

PMID- 9009927
TI  - Orthodontic and temporomandibular joint considerations in treatment of patients
      with Ehlers-Danlos syndrome.
AB  - The gross clinical manifestations, the classifications of the syndrome, and a
      summary of the pathophysiology are presented. Dental manifestations are described
      with an emphasis on the orthodontic and temporomandibular joint problems found in
      the disease. Finally, there are short clinical reports of orthodontic and
      surgical temporomandibular joint treatments.

PMID- 9009928
TI  - Selcuk type headgear-timer (STHT).
AB  - The Selcuk type headgear-timer (STHT) is described and tested under laboratory
      conditions first and then in a controlled patient study. The timing device was
      compared with real time measurements for 4 months. Accuracy was determined to be
      absolute (100%). The STHT was determined to be independent of force variables,
      easy to construct, rugged, and inexpensive. In the clinical test, 10 patients
      were instructed to wear the extraoral appliance for 16 hours a day. After a 2
      month treatment period, the timing mechanisms were introduced to the patients and
      a subsequent 2-month treatment period was initiated. At the end of the second
      period, headgear wear was increased 26%. This significant improvement in patient
      compliance with the STHT timing device, attached to a standard breakaway type
      headgear, has the likelihood of enhancing treatment results. A foolproof method
      of assessing actual duration of wear is now available.

PMID- 9009929
TI  - Treatment of a patient with a Class II malocclusion and an extremely high
      mandibular plane angle and severe crowding.

PMID- 9009930
TI  - An adult malocclusion requiring a combination of orthodontic and prosthodontic
      treatment.
AB  - An adult malocclusion with deficient maxillary lip support caused by missing
      maxillary lateral incisors is presented. The malocclusion was treated with a
      nonstandard opening of pontic spaces for anterior prosthetic bridge replacement
      approach. [This case report was presented to the American Board of Orthodontics
      as Case 2, in partial fulfillment of the requirements for the certification
      process conducted by the Board.]

PMID- 9009931
TI  - Creating composite image files with a word processor.

PMID- 9009932
TI  - Reflecting on the orthodontic educational development symposium.

PMID- 9009933
TI  - Nerve blocks in the evaluation of chronic pain.

PMID- 9009934
TI  - Cricoid cartilage pressure decreases lower esophageal sphincter tone.
AB  - BACKGROUND: Cricoid cartilage pressure induced to prevent pulmonary aspiration
      from regurgitation of gastric contents has been recommended, and its efficacy
      requires a force greater than 40 Newtons. For regurgitation to occur, both an
      increase in gastric pressure and relaxation of the lower esophageal sphincter
      (LES) are necessary. However, the effect of cricoid cartilage pressure on the LES
      is unknown. This study evaluated the effects of cricoid cartilage pressure on LES
      in human volunteers. METHODS: Lower esophageal sphincter and esophageal barrier
      pressures (which equals LES pressure-gastric pressure) were measured using a
      manometric method in eight unanesthetized volunteers (4 men, 4 women) classified
      as American Society of Anesthesiologists physical status 1. The force applied to
      the cricoid cartilage was measured continuously, and LES pressure was recorded at
      a cricoid force of 20 and 40 Newtons. RESULTS: Cricoid pressure decreased LES
      pressure from 24 +/- 3 mmHg to 15 +/- 4 mmHg at a force of 20 Newtons (P < 0.05)
      and to 12 +/- 4 mmHg with a force of 40 Newtons (P < 0.01). CONCLUSIONS: These
      findings may explain the occurrence of pulmonary aspiration before tracheal
      intubation despite application of cricoid cartilage pressure.

PMID- 9009935
TI  - Influence of age and gender on the pharmacokinetics and pharmacodynamics of
      remifentanil. I. Model development.
AB  - BACKGROUND: Previous studies have reported conflicting results concerning the
      influence of age and gender on the pharmacokinetics and pharmacodynamics of
      fentanyl, alfentanil, and sufentanil. The aim of this study was to determine the
      influence of age and gender on the pharmacokinetics and pharmacodynamics of the
      new short-acting opioid remifentanil. METHODS: Sixty-five healthy adults (38 men
      and 27 women) ages 20 to 85 y received remifentanil by constant-rate infusion of
      1 to 8 micrograms.kg-1.min-1 for 4 to 20 min. Frequent arterial blood samples
      were drawn and assayed for remifentanil concentration. The electroencephalogram
      was used as a measure of drug effect. Population pharmacokinetic and
      pharmacodynamic modeling was performed using the software package NONMEM. The
      influence of volunteer covariates were analyzed using a generalized additive
      model. The performances of the simple (without covariates) and complex (with
      covariates) models were evaluated prospectively in an additional 15 healthy
      participants ages 41 to 84 y. RESULTS: The parameters for the simple three
      compartment pharmacokinetic model were V1 = 4.98 l, V2 = 9.01 l, V3 = 6.54 l, Cl1
      = 2.46 l/min, Cl2 = 1.69 l/min, and Cl3 = 0.065 l/min. Age and lean body mass
      were significant covariates. From the ages of 20 to 85 y, V1 and Cl1 decreased by
      approximately 25% and 33%, respectively. The parameters for the simple sigmoid
      Emax pharmacodynamic model were Ke0 = 0.516 min-1, E0 = 20 Hz, Emax = 5.62 Hz,
      EC50 = 11.2 ng/ml, and gamma = 2.51. Age was a significant covariate of EC50 and
      Ke0, with both decreasing by approximately 50% for the age range studied. The
      complex pharmacokinetic-pharmacodynamic model performed better than did the
      simple model when applied prospectively. CONCLUSIONS: This study identified (1)
      an effect of age on the pharmacokinetics and pharmacodynamics of remifentanil;
      (2) an effect of lean body mass on the pharmacokinetic parameters; and (3) no
      influence of gender on any pharmacokinetic or pharmacodynamic parameter.

PMID- 9009936
TI  - Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application.
AB  - BACKGROUND: The pharmacokinetics and pharmacodynamics of remifentanil were
      studied in 65 healthy volunteers using the electroencephalogram (EEG) to measure
      the opioid effect. In a companion article, the authors developed complex
      population pharmacokinetic and pharmacodynamic models that incorporated age and
      lean body mass (LBM) as significant covariates and characterized intersubject
      pharmacokinetic and pharmacodynamic variability. In the present article, the
      authors determined whether remifentanil dosing should be adjusted according to
      age and LBM, or whether these covariate effects were overshadowed by the
      interindividual variability present in the pharmacokinetics and pharmacodynamics.
      METHODS: Based on the typical pharmacokinetic and pharmacodynamic parameters,
      nomograms for bolus dose and infusion rates at each age and LBM were derived.
      Three populations of 500 individuals each, ages 20, 50, and 80 yr, were simulated
      base on the interindividual variances in model parameters as estimated by the
      NONMEM software package. The peak EEG effect in response to a bolus, the steady
      state EEG effect in response to an infusion, and the time course of drug effect
      were examined in each of the three populations. Simulations were performed to
      examine the time necessary to achieve a 20%, 50%, and 80% decrease in
      remifentanil effect site concentration after a variable-length infusion. The
      variability in the time for a 50% decrease in effect site concentrations was
      examined in each of the three simulated populations. Titratability using a
      constant-rate infusion was also examined. RESULTS: After a bolus dose, the age
      related changes in V1 and Ke0 nearly offset each other. The peak effect site
      concentration reached after a bolus dose does not depend on age. However, the
      peak effect site concentration occurs later in elderly individuals. Because the
      EEG shows increased brain sensitivity to opioids with increasing age, an 80-yr
      old person required approximately one half the bolus dose of a 20-yr old of
      similar LBM to reach the same peak EEG effect. Failure to adjust the bolus dose
      for age resulted in a more rapid onset of EEG effect and prolonged duration of
      EEG effect in the simulated elderly population. The infusion rate required to
      maintain 50% EEG effect in a typical 80-yr old is approximately one third that
      required in a typical 20-yr old. Failure to adjust the infusion rate for age
      resulted in a more rapid onset of EEG effect and more profound steady-state EEG
      effect in the simulated elderly population. The typical times required for
      remifentanil effect site concentrations to decrease by 20%, 50%, and 80% after
      prolonged administration are rapid and little affected by age or duration of
      infusion. These simulations suggest that the time required for a decrease in
      effect site concentrations will be more variable in the elderly. As a result,
      elderly patients may occasionally have a slower emergence from anesthesia than
      expected. A step change in the remifentanil infusion rate resulted in a rapid and
      predictable change of EEG effect in both the young and the elderly. CONCLUSIONS:
      Based on the EEG model, age and LBM are significant demographic factors that must
      be considered when determining a dosage regimen for remifentanil. This remains
      true even when interindividual pharmacokinetic and pharmacodynamic variability
      are incorporated in the analysis.

PMID- 9009937
TI  - Local anesthetic administration for awake direct laryngoscopy. Are
      glossopharyngeal nerve blocks superior?
AB  - BACKGROUND: Glossopharyngeal nerve (GPN) blocks may provide reliable analgesia
      for awake direct laryngoscopy, although this has not been evaluated
      prospectively. This study was designed to determine if GPN blocks provide a
      superior route of local anesthetic administration for awake direct laryngoscopy
      as measured by hemodynamic, gag, and subjective pain responses. METHODS: A
      prospective, randomized, single-blinded, crossover design was used. All
      participants (n = 11) were anesthesiologists. Three routes of local anesthetic
      administration were evaluated: 2 min of 2% viscous lidocaine swish and gargle
      (S&G); S&G combined with 10% lidocaine spray (S&G/spray); and S&G combined with
      1% lidocaine bilateral GPN blocks (S&G/block; anterior tonsillar pillar method).
      Five minutes after the local anesthetic was administered, laryngoscopy was
      performed and sustained for 20 s. Noninvasive hemodynamic measurements and serum
      lidocaine concentrations were determined. Visual analogue scale scores and a
      poststudy questionnaire were used to assess participants' ability to tolerate
      local anesthetic administration and laryngoscopy and their choice for use in
      clinical practice. RESULTS: No significant hemodynamic changes were observed,
      although there was a modest increase (< 15%) in heart rate in the S&G/block group
      in the first minute after laryngoscopy. Serum lidocaine concentrations were
      higher (P < 0.05) in the S&G/block group at 5 and 10 min (0.5 +/- 0.1 and 1.0 +/-
      0.2 microgram/ml) compared with the S&G group. Participants' visual analogue
      scale scores, which assessed their ability to tolerate laryngoscopy, showed that
      S&G (5.4 +/- 0.9) resulted in more discomfort (P < 0.05) than either S&G/spray
      (3.5 +/- 0.9) or S&G/block (3.3 +/- 0.7). The laryngoscopist's visual analogue
      scale scores, which assessed the ease of visualization, revealed a trend (P <
      0.08) toward less coughing and gagging with S&G/spray (1.8 +/- 0.9) compared with
      S&G (4.0 +/- 1.3) and S&G/block (3.7 +/- 1.1). Oropharyngeal discomfort lasting
      24 h or more was reported by 91% of participants after S&G/block, whereas no
      participant reported oropharyngeal discomfort after S&G or S&G/spray.
      Significantly more participants (73%) indicated their preference for using
      S&G/spray in future clinical practice compared with S&G (P < 0.01) and S&G/block
      (P < 0.05). CONCLUSIONS: Glossopharyngeal nerve blocks do not provide a superior
      route of local anesthetic administration for awake direct laryngoscopy. Two
      minutes of 2% viscous lidocaine S&G followed by 10% lidocaine spray was the
      anesthetic route preferred by participants and laryngoscopists.

PMID- 9009938
TI  - Changes in cerebrospinal fluid pressure and lactate concentrations during
      thoracoabdominal aortic aneurysm surgery.
AB  - BACKGROUND: Although ischemic injury to the spinal cord is a well-known
      complication of aortic surgery, no metabolic markers have been identified as
      predictors of an adverse outcome. This study evaluated the effect of
      cerebrospinal fluid (CSF) drainage, with and without distal femoral perfusion or
      moderate hypothermia on blood and CSF lactate concentrations and CSF pressure
      during thoracoabdominal aortic aneurysm surgery. METHODS: Three nonconcurrent
      groups of patients were studied prospectively: patients with normal body
      temperature (35 degrees C) but without distal femoral bypass (n = 6), patients
      with normal body temperature with bypass (n = 7), and patients with hypothermia
      (30 degrees C) and bypass (n = 8). In all patients, CSF pressure was recorded
      before, during, and after aortic cross-clamping. During the surgical repair, CSF
      drainage was performed using a 4-Fr intrathecal silicone catheter. Blood and CSF
      lactate concentrations were measured throughout the operation. RESULTS:
      Significant increases in blood (490%) and CSF (173%) lactate concentrations were
      observed during and after thoracic aortic occlusion in patients with normothermia
      and no bypass (P < 0.02 and 0.05, respectively). Distal perfusion attenuated the
      increase in both blood and CSF lactate (P < 0.01), and a further reduction was
      achieved with hypothermia of 30 degrees C (P < 0.001). Patients who became
      paraplegic showed a greater increase in CSF lactate concentrations after aortic
      clamp release compared with those who suffered no neurological damage (275% vs.
      123% of baseline; P < 0.05). Increased CSF pressure of 42-60% (P < 0.005) was
      noted soon after thoracic aortic occlusion, both with and without distal femoral
      bypass. CONCLUSIONS: Incremental reductions in CSF lactate concentrations were
      achieved using distal femoral bypass and hypothermia. The reduction in CSF
      lactate correlated with the methods used to protect the spinal cord during
      thoracoabdominal aortic aneurysm surgery and was associated with better outcome.
      Decompression by distal bypass of the hemodynamic overload caused by aortic
      occlusion was insufficient to eliminate the acute increase in CSF pressure.
      Cerebrospinal fluid lactate measurements during high aortic surgery may
      accurately represent the spinal cord metabolic balance.

PMID- 9009939
TI  - Improving the design of muscle relaxant studies. Stabilization period and tetanic
      recruitment.
AB  - BACKGROUND: The results from studies of muscle relaxants show wide variations
      among institutions. The authors hypothesized that some of this variability could
      be explained by differences in duration of nerve stimulation before drug
      administration (stabilization period). METHODS: Train-of-four stimulation was
      applied every 12 s to both ulnar nerves and adductor pollicis twitch tension was
      measured in anesthetized participants given 30 micrograms/kg vecuronium. In phase
      1, the stabilization period was > 30 min for both extremities. In phase 2-4,
      stabilization period was 20 min for one extremity and 2 min for the other. In
      addition, in phase 3, a 2-s 50-Hz tetanus initiated the 2-min stimulation period;
      in phase 4, duration of tetanus was 5 s. Twitch recovery was recorded until
      stable for more than 15 min. Time to 25% recovery (clinical duration) was
      calculated based on two indices: predrug and final (recovery) twitch tension.
      Values for onset and clinical duration were compared by paired parametric and
      nonparametric tests. RESULTS: In phase 1, predrug and recovery twitch tension
      were similar in each extremity, and onset and clinical duration did not differ
      between extremities, permitting paired comparisons in remaining studies. In phase
      2, onset was more rapid with 20-min of prestimulation. With 20-min
      prestimulation, predrug and recovery twitch tension were similar; with 2-min
      prestimulation, recovery twitch tension exceeded predrug values. When referenced
      to predrug twitch tension, clinical duration was shorter with 2-min, that with 20
      min prestimulation. Initiating stimulation with 2-s or 5-s 50-Hz tetani (phases
      3, 4) abolished differences between extremities in onset and recovery.
      CONCLUSIONS: With only train-of-four stimulation (no tetani), onset and clinical
      duration vary with duration of prestimulation, suggesting that a brief period of
      predrug stimulation is inadequate. However, lengthy prestimulation may be
      impractical in clinical studies. Tetanic stimulation for 2 or 5 s obviates the
      need for prolonged stabilization during studies of muscle relaxants.

PMID- 9009940
TI  - Incidence of neurologic complications related to thoracic epidural
      catheterization.
AB  - BACKGROUND: Due to potential neurologic sequelae, the risk:benefit ratio of
      thoracic epidural analgesia is controversial. Surprisingly, however, few
      available data address neurologic complications. The incidence of neurologic
      complications occurring after thoracic epidural catheterization was studied in
      patients scheduled for abdominal or abdominothoracic surgery. METHODS: A total of
      4,185 patients were studied, including 2,059 during the prospective phase of the
      study and 2,126 during the retrospective phase. After thoracic epidural
      catheterization, all patients received general anesthesia. Patients' neurologic
      status was assessed by an anesthesiologist using clinical criteria after
      operation and after epidural catheter removal. If neurologic complications were
      suspected, a neurologist was consulted. The incidence of specific complications
      was compared for different thoracic puncture sites: upper (T3/4-6/7), mid (T7/8
      8/9), and lower (T9/10-11/12) catheter insertion levels. RESULTS: The overall
      incidence of complications after thoracic epidural catheterization was 3.1% (n =
      128). This included dural perforation (0.7%; n = 30); unsuccessful catheter
      placement (1.1%; n = 45); postoperative radicular type pain (0.2%; n = 9),
      responsive to catheter withdrawal in all cases; and peripheral nerve lesions
      (0.6%; n = 24), 0.3% (n = 14) of which were peroneal nerve palsies probably
      related to surgical positioning or other transient peripheral nerve lesions
      (0.2%; n = 10). No signs suggesting epidural hematoma were recognized, and there
      were no permanent sensory or motor defects attributable to epidural
      catheterization. Unintentional dural perforation was observed significantly more
      often in the lower (3.4%) than in the mid (0.9%), or upper (0.4%) thoracic
      region. A single patient experienced severe respiratory depression after
      receiving epidural buprenorphine but recovered without sequelae. CONCLUSIONS:
      Thoracic epidural catheterization for abdominal and thoracoabdominal surgery is
      not associated with a high incidence of serious neurologic complications. In
      fact, the incidence of puncture- and catheter-related complications is less in
      the mid and upper than in lower thoracic region, and the predicted maximum risk
      for permanent neurologic complications (upper bound of the 95% confidence
      interval) is 0.07%.

PMID- 9009941
TI  - Mechanisms whereby propofol mediates peripheral vasodilation in humans.
      Sympathoinhibition or direct vascular relaxation?
AB  - BACKGROUND: Anesthetic induction and maintenance with propofol are associated
      with decreased blood pressure that is, in part, due to decreased peripheral
      resistance. Several possible mechanisms whereby propofol could reduce peripheral
      resistance include a direct action of propofol on vascular smooth muscle, an
      inhibition of sympathetic activity to the vasculature, or both. This study
      examined these two possibilities in humans by measuring the forearm vascular
      responses to infusions of propofol into the brachial artery (study 1) and by
      determining the forearm arterial and venous responses to systemic (intravenous)
      infusions of propofol after sympathetic denervation of the forearm by stellate
      blockade (study 2). METHODS: Bilateral forearm venous occlusion plethysmography
      was used to examine forearm vascular resistance (FVR) and forearm vein compliance
      (FVC). Study 1 used infusion of intralipid (time control) and propofol at rates
      between 83 and 664 micrograms/min into the brachial artery of 11 conscious
      persons and compared responses to arterial infusions of sodium nitroprusside
      (SNP) at 0.3, 3.0, and 10 micrograms/min. Venous blood from the infusion arm was
      assayed for plasma propofol concentrations. In study 2, after left stellate block
      (12 ml 0.25% bupivacaine + 1% lidocaine), six participants were anesthetized and
      maintained with propofol infusions of 125 and 200 micrograms.kg-1.min-1.
      Simultaneous right forearm (unblocked) blood flow dynamics served as the time
      control. In three additional conscious participants, intrabrachial artery
      infusions of SNP and nitroglycerin, both at 10 micrograms/min, were performed
      before and after stellate blockade of the left forearm to determine whether the
      sympathetically denervated forearm vessels could dilate beyond the level produced
      by denervation alone. RESULTS: In study 1, infusion of intralipid or propofol
      into the brachial artery did not change FVR or FVC. Sodium nitroprusside
      significantly decreased FVR in a dose-dependent manner by 22 +/- 5%, 65 +/- 3%,
      and 78 +/- 2% (mean +/- SEM) but did not change FVC. During the incremental
      propofol infusions, plasma propofol concentrations increased from 0.2 to 10.1
      micrograms/ml and averaged 7.4 +/- 1.1 micrograms/ml during the highest infusion
      rate. In study 2, stellate ganglion blockade decreased FVR by 50 +/- 6% and
      increased FVC by 58 +/- 10%. Propofol anesthesia at 125 and 200 micrograms.kg
      1.min-1 progressively reduced mean arterial pressure. In the arm with sympathetic
      denervation, FVR and FVC showed no further changes during propofol anesthesia,
      whereas in the control arm FVR significantly decreased by 41 +/- 9% and 42 +/-
      7%, and FVC increased significantly by 89 +/- 27% and 85 +/- 32% during 125 and
      200 micrograms.kg-1.min-1 infusions of propofol, respectively. In the three
      additional conscious participants, intraarterial infusion of SNP and
      nitroglycerin (TNG) after the stellate blockade resulted in a further decrease of
      FVR and a further increase of FVC. CONCLUSIONS: In contrast to SNP infusions,
      propofol infusions into the brachial artery of conscious persons caused no
      significant vascular responses, despite the presence of therapeutic plasma
      concentrations of propofol within the forearm. The effects of propofol anesthesia
      on FVR and FVC are similar to the effects of sympathetic denervation by stellate
      ganglion blockade. Thus the peripheral vascular actions of propofol appear to be
      due primarily to an inhibition of sympathetic vasoconstrictor nerve activity.

PMID- 9009942
TI  - Decreased thiopental requirements in early pregnancy.
AB  - BACKGROUND: Anesthetic requirements for inhalational agents are decreased during
      pregnancy, but there are no data regarding requirements for intravenous agents.
      The quantal dose-response curves for thiopental were calculated for 70
      nonpregnant women having gynecologic surgery and for 70 pregnant women of 7-13
      weeks' gestation having elective abortions. METHODS: Groups of 10 patients were
      given 2, 2.4, 2.8, 3.3, 3.8, 4.5, or 5.3 mg/kg thiopental as a bolus dose during
      a period of 10 s. Two minutes later, patients were asked to open their eyes as a
      test for hypnosis. Patients who did not open their eyes were given a 10-s, 50-Hz,
      80-mA transcutaneous tetanic electrical stimulus to the ulnar nerve as a test for
      anesthesia. Purposeful movement indicated that there was no anesthesia. Log dose
      response curves for hypnosis and anesthesia were calculated after logit
      transformation. RESULTS: In the nonpregnant women, the median effective doses
      (ED50s) (95% confidence interval) for hypnosis and anesthesia were 3.1 (2.8-3.4)
      mg/kg and 4.9 (4.5-5.4) mg/kg, whereas in the pregnant women the corresponding
      ED50s were 2.6 (2.3-2.8) mg/kg and 4 (3.7-4.4) mg/kg. In the non-pregnant women,
      the ED95s (95% CI) for hypnosis and anesthesia were 4.4 (3.9-5.4) mg/kg and 6.4
      (5.7-7.9) mg/kg, whereas in the pregnant women the corresponding ED95s were 3.7
      (3.3-4.5) mg/kg and 5.2 (4.7-6.3) mg/kg. The pregnant to nonpregnant relative
      median potency (95% CI) ratio for hypnosis was 0.83 (0.67-0.96) and for
      anesthesia it was 0.82 (0.62-0.94). CONCLUSIONS: The dose of thiopental for
      hypnosis was 17% less and that for anesthesia was 18% less in pregnant women of 7
      13 weeks' gestation compared with that in nonpregnant women.

PMID- 9009943
TI  - Effects of proportional assist ventilation on inspiratory muscle effort in
      patients with chronic obstructive pulmonary disease and acute respiratory
      failure.
AB  - BACKGROUND: Acute respiratory failure may develop in patients with chronic
      obstructive pulmonary disease because of intrinsic positive end-expiratory
      pressure (PEEPi) and increased resistive and elastic loads. Proportional assist
      ventilation is an experimental mode of partial ventilatory support in which the
      ventilator generates flow to unload the resistive burden (flow assistance: FA)
      and volume to unload the elastic burden (volume assistance: VA) proportionally to
      inspiratory muscle effort, and PEEPi can be counterbalanced by application of
      external PEEP. The authors assessed effects of proportional assist ventilation
      and optimal ventilatory settings in patients with chronic obstructive pulmonary
      disease and acute respiratory failure. METHODS: Inspiratory muscles and
      diaphragmatic efforts were evaluated by measurements of esophageal, gastric, and
      transdiaphragmatic pressures. Minute ventilation and breathing patterns were
      evaluated by measuring airway pressure and flow. Measurements were performed
      during spontaneous breathing, continuous positive airway pressure, FA, FA+PEEP,
      VA, VA+PEEP, FA+VA, and FA+VA+PEEP. RESULTS: FA+PEEP provided the greatest
      improvement in minute ventilation (89 +/- 3%) and dyspnea (62 +/- 2%). The
      largest reduction in pressure time product per breath of the respiratory muscles
      and diaphragm (44 +/- 3% and 33 +/- 2%, respectively) also was observed during
      FA+PEEP condition. When VA was added to this setting, a reduction in respiratory
      rate (50 +/- 3%), an increase in inspiratory time (102 +/- 6%), and a further
      reduction in pressure time product per minute (65 +/- 2% and 64% for the
      respiratory muscles and diaphragm, respectively) was observed. However, values of
      pressure time product per liter of minute ventilation during FA+VA+PEEP did not
      differ with those observed during FA+PEEP condition. Worsening of patient
      ventilator interaction and breathing asynchrony occurred when VA was implemented.
      CONCLUSIONS: Application of PEEP to counterbalance PEEPi and FA to unload the
      resistive burden provided the optimal conditions in such patients. Ventilator
      over-assistance and patient-ventilator asynchrony was observed when VA was added
      to this setting. The clinical use of proportional assist ventilation should be
      based on continuous measurements of respiratory mechanics.

PMID- 9009944
TI  - Hospital costs and severity of illness in three types of elective surgery.
AB  - BACKGROUND: If patients who are more severely ill have greater hospital costs for
      surgery, then health-care reimbursements need to be adjusted appropriately so
      that providers caring for more seriously ill patients are not penalized for
      incurring higher costs. The authors' goal for this study was to determine if
      severity of illness, as measured by either the American Society of
      Anesthesiologists Physical Status (ASA PS) or the comorbidity index developed by
      Charlson, can predict anesthesia costs, operating room costs, total hospital
      costs, or length of stay for elective surgery. METHODS: The authors randomly
      selected 224 inpatients (60% sampling fraction) having either colectomy (n = 30),
      total knee replacement (n = 100), or laparoscopic cholecystectomy (n = 94) from
      September 1993 to September 1994. For each surgical procedure, backward
      elimination multiple regression was used to build models to predict (1) total
      hospital costs, (2) operating room costs, (3) anesthesia costs, and (4) length of
      stay. Explanatory candidate variables included patient age (years), sex, ASA PS,
      Charlson comorbidity index (which weighs the number and seriousness of coexisting
      diseases), and type of insurance (Medicare/Medicaid, managed care, or indemnity).
      These analyses were repeated for the pooled data of all 224 patients. Costs (not
      patient charges) were obtained from the hospital cost accounting software.
      RESULTS: Mean total hospital costs were $3,778 (95% confidence interval +/- 299)
      for laparoscopic cholecystectomy, $13,614 (95% CI +/- 3,019) for colectomy, and
      $18,788 (95% CI +/- 573) for knee replacement. The correlation (r) between ASA PS
      and Charlson comorbidity scores equaled 0.34 (P < .001). No consistent relation
      was found between hospital costs and either of the two severity-of-illness
      indices. The Charlson comorbidity index (but not the ASA PS) predicted hospital
      costs only for knee replacement (P = .003). The ASA PS, but not the Charlson
      index, predicted operating room and anesthesia costs only for colectomy (P <
      .03). CONCLUSIONS: Severity of illness, as categorized by ASA PS categories 1-3
      or by the Charlson comorbidity index, was not a consistent predictor of hospital
      costs and lengths of stay for three types of elective surgery. Hospital resources
      for these lower-risk elective procedures may be expended primarily to manage the
      consequences of the surgical disease, rather than to manage the patient's
      coexisting diseases.

PMID- 9009945
TI  - The effects of motion on the performance of pulse oximeters in volunteers
      (revised publication).
AB  - BACKGROUND: Pulse oximetry is considered a standard of care in both the operating
      room and the postanesthetic care unit, and it is widely used in all critical care
      settings. Pulse oximeters may fail to provide valid SpO2 data in various
      situations that produce low signal-to-noise ratio. Motion artifact is a common
      cause of oximeter failure and loss of accuracy. This study compares the accuracy
      and data dropout rates of three current pulse oximeters during standardized
      motion in healthy volunteers. METHODS: Ten healthy volunteers were monitored by
      three different pulse oximeters: Nellcor N-200, Nellcor N-3000, and Masimo SET
      (prototype). Sensors were placed on digits 2, 3, and 4 of the test hand, which
      was strapped to a mechanical motion table. The opposite hand was used as a
      stationary control and was monitored with the same pulse oximeters and an
      arterial cannula. Arterial oxygen saturation was varied from 100% to 75% by
      changing the inspired oxygen concentration. While SpO2 was both constant and
      changing, the oximeter sensors were connected before and during motion. Oximeter
      errors and dropout rates were digitally recorded continuously during each
      experiment. RESULTS: If the oximeter was functioning before motion began, the
      following are the percentages of time when the instrument displayed an SpO2 value
      within 7% of control: N-200 = 76%, N-3000 = 87%, and Masimo = 99%. When the
      oximeter sensor was connected after the beginning of motion, the values were N
      200 = 68%, N-3000 = 47%, and Masimo = 97%. If the alarm threshold was chosen SpO2
      less than 90%, then the positive predictive values (true alarms/total alarms) are
      N-200 = 73%, N-3000 = 81%, and Masimo = 100%. In general, N-200 had the greatest
      SpO2 errors and N-3000 had the highest dropout rates. CONCLUSIONS: The mechanical
      motions used in this study significantly affected oximeter function, particularly
      when the sensors were connected during motion, which requires signal acquisition
      during motion. The error and dropout rate performance of the Masimo was superior
      to that of the other two instruments during all test conditions. Masimo uses a
      new paradigm for oximeter signal processing, which appears to represent a
      significant advance in low signal-to-noise performance.

PMID- 9009946
TI  - Isoflurane and halothane increase adenosine triphosphate preservation, but do not
      provide additive recovery of function after ischemia, in preconditioned rat
      hearts.
AB  - BACKGROUND: Brief ischemic periods render the myocardium resistant to infarction
      from subsequent ischemic insults by a process called ischemic preconditioning.
      Volatile anesthetics have also been shown to be cardioprotective if administered
      before ischemia. The effect of preconditioning alone and combined with halothane
      or isoflurane on hemodynamic recovery and preservation of adenosine triphosphate
      content in isolated rat hearts was evaluated. METHODS: Seven groups of isolated
      rat hearts (n = 6 each) were perfused in a retrograde manner at constant
      temperature and pressure. A latex balloon was placed in the left ventricle to
      obtain isovolumetric contraction. Heart rhythm, coronary flow, left ventricular
      pressure and its derivative dP/dt (positive and negative), and developed pressure
      were monitored. The hearts were paced at 300 beats per minute. Each heart was
      randomly allocated to (1) a time-control group that received no ischemia, (2) an
      untreated group that received 25 min of normothermic ischemia only. (3 and 4) an
      isoflurane group and a halothane group that received 40 min of anesthetic (2.2%
      and 1.5%, respectively) before ischemia; (5) a preconditioning group that
      received two 5-min periods of ischemia separated by 10 min of reperfusion before
      ischemia; or (6 and 7) a isoflurane+preconditioning group and a
      halothane+preconditioning group that received anesthetic for 10 min at
      concentrations of 2.2% or 1.5%, respectively, before two 5-min periods of
      ischemia separated by 10 min of reperfusion. All treated groups received 25 min
      of normothermic ischemia followed by 30 min of reperfusion. RESULTS: The time
      control group remained hemodynamically stable for the entire experiment, and the
      adenosine triphosphate content was 18.3 +/- 1.7 (SEM) microM/g at the end of 115
      min. The untreated group had depressed recovery after 25 min of normothermic
      ischemia, and the developed pressure was significantly depressed and recovered
      only 30 +/- 9% (P < 0.001) of its preischemic value. There was also a significant
      increase in the incidence of ventricular fibrillation (P < 0.001). Adenosine
      triphosphate content was significantly lower in this group than in all other
      groups. Five minutes of ischemia in the preconditioning group had little effect
      on hemodynamics and decreased developed pressure only 6.4%. Halothane depressed
      developed pressure by 16 +/- 5% (P < 0.001), and isoflurane increased coronary
      flow by 145 +/- 9% (P < 0.001) but had no significant hemodynamic effect. The
      treated groups had significantly better recovery of postischemic function than
      did the untreated group. In the preconditioning group, developed pressure
      recovered to 85% of control and dP/dt+ to 87% of control. The addition of
      halothane or isoflurane to preconditioning did not provide additional functional
      recovery but did increase the level of adenosine triphosphate preservation (13.1
      +/- 1.1 and 12.4 +/- 1.1 microM/g, respectively). CONCLUSIONS: The results
      indicate that preconditioning, halothane, and isoflurane provide significant
      protection against ischemia. The combination of preconditioning and halothane or
      isoflurane did not improve hemodynamic recovery but did increase preservation of
      adenosine triphosphate.

PMID- 9009947
TI  - Isoflurane and sevoflurane interact with the nicotinic acetylcholine receptor
      channels in micromolar concentrations.
AB  - BACKGROUND: This study was performed to elucidate and compare the effects of
      sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse
      myotubes. The experiments were done with special reference to anesthetic
      concentrations considerably less than those used for clinical anesthesia.
      METHODS: The patch-clamp technique was used to record acetylcholine-activated
      currents from the embryonic type of the nicotinic acetylcholine receptor in the
      outside-out mode. A piezo-driven liquid filament switch was used for the
      ultrafast application of acetylcholine alone or in combination with isoflurane or
      sevoflurane. In addition, the patches were preexposed to either anesthetic,
      preceding the activation with acetylcholine. RESULTS: The current elicited by
      acetylcholine was reduced reversibly and in a concentration-dependent manner by
      both anesthetics, which were equally effective. Preexposure of the patches to
      isoflurane or sevoflurane showed an additional inhibition that was present at
      micromolar concentrations. The time courses of current decay could be fitted by
      single exponentials for isoflurane. At higher concentrations of sevoflurane, the
      current decay became biexponential. In contrast to isoflurane, sevoflurane
      increased the time constants of desensitization when applied in low
      concentrations. CONCLUSIONS: At the nicotinic acetylcholine receptor, isoflurane
      and sevoflurane act primarily through the same mechanisms: Both affect the open
      and the closed state of the channels in concentrations equal to and less than
      those encountered clinically. The kinetics of desensitization, however, are
      altered in a different manner. Thus there may be several different sites of
      interaction.

PMID- 9009948
TI  - Isoflurane attenuates early neutrophil-independent hypoxia-reoxygenation injuries
      in the reperfused liver in fasted rats.
AB  - BACKGROUND: Ischemia-hypoxia followed by reperfusion and reoxygenation injures
      cells and organs. Previous studies have indicated that isoflurane may protect
      organs from ischemia-reperfusion or hypoxia-reoxygenation. This study
      investigated the ability of isoflurane to protect the liver from hypoxia
      reoxygenation injury and the mechanisms of this phenomenon. METHODS: The isolated
      liver was perfused at a constant pressure of 12 cm H2O with a modified Krebs
      Ringer-bicarbonate solution saturated with a 95% oxygen/5% carbon dioxide gas
      mixture. Hypoxic perfusion produced by decreasing the oxygen concentration in the
      gas mixture to 10% was followed by perfusion at 95% oxygen for 60 min. Viability
      of the liver was assessed by lactate dehydrogenase release from the liver.
      Isoflurane at 0.5, 1, and 2 minimum alveolar concentration was administered to
      assess the effect of isoflurane on hypoxia-reperfusion injury. To determine the
      effect of isoflurane on extracellular generation of superoxide in the liver, the
      reduction of ferricytochrome c with or without superoxide dismutase was measured.
      RESULTS: Lactate dehydrogenase release was transiently but dramatically increased
      by reoxygenation and significantly attenuated by 1 and 2 minimum alveolar
      concentration of isoflurane. Suppression of Kupffer cells with gadolinium
      chloride also attenuated the lactate dehydrogenase release. Isoflurane
      significantly reduced the superoxide generation on reperfusion. CONCLUSIONS: The
      results show that isoflurane protected the liver from an early reoxygenation
      injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory
      effects of isoflurane on the injury may involve suppression of extracellular
      superoxide generation during reoxygenation.

PMID- 9009949
TI  - Initial contractile response of isolated rat heart cells to halothane, enflurane,
      and isoflurane.
AB  - BACKGROUND: In several beating cardiac muscle preparations, a short-lived
      increase in twitch tension or amplitude has been observed when they were exposed
      abruptly to solutions containing halothane or enflurane. As exposure to the
      anesthetics was continued, the expected negative inotropic effect became evident
      after the short-lived increase in twitch. No such increase in twitch has been
      reported during exposure to isoflurane. It has been hypothesized that this short
      lived increase in twitch is caused by an enhancement of calcium release from the
      sarcoplasmic reticulum, but other mechanisms have not been excluded. METHODS:
      Freshly isolated, single rat ventricular cells were stimulated to beat at room
      temperature and abruptly exposed to solutions containing halothane (0.25-0.64
      mM), enflurane (0.69-1 mM), or isoflurane (0.31-0.54 mM). During these exposures,
      twitch amplitude was measured and intracellular calcium concentration was
      followed using the calcium-sensitive dye indo-1. In some experiments, the whole
      cell patch-clamp technique was used to measure membrane current. In addition, in
      several cells the sarcoplasmic reticulum calcium content was assessed through the
      response to brief pulses of caffeine. RESULTS: Both the twitch amplitude and the
      intracellular calcium transient were increased temporarily in cells abruptly
      exposed to halothane or enflurane. No such behavior was found with isoflurane.
      After continued exposure to all three agents, both the twitch amplitude and the
      calcium transient were less than control. During the beats exhibiting an increase
      in twitch, no alteration in the relation between cell length (twitch amplitude)
      and the intracellular calcium transient was found compared with control
      conditions. In addition, the temporary increase in twitch amplitude occurred in
      cells contracting under voltage-clamp control when halothane was introduced, and
      it was not associated with any increase in the calcium current. The sarcoplasmic
      reticulum calcium content at the time of the halothane-induced increase in twitch
      also was not increased. CONCLUSIONS: The short-lived increase in twitch after
      abrupt exposure to halothane or enflurane is related to increased intracellular
      calcium during the beat and not to any changes in myofilament sensitivity to
      calcium. Because these results eliminate most alternative explanations for this
      phenomenon, the authors conclude that halothane, and probably also enflurane,
      increases the fraction of calcium released from the sarcoplasmic reticulum with
      each heart beat. Isoflurane appears to lack this action.

PMID- 9009950
TI  - Interaction of halothane with alpha- and beta-adrenoceptor stimulations in rat
      myocardium.
AB  - BACKGROUND: Halothane induces negative inotropic and lusitropic effects in
      myocardium. It has been suggested that halothane potentiates beta-adrenoceptor
      stimulation. However, its effects on the inotropic response to alpha-adrenoceptor
      stimulation and its effects on the lusitropic effects of alpha- and beta
      adrenoceptor stimulation are unknown. METHODS: The effects of halothane (0.5 and
      1 minimum alveolar concentration [MAC]) on the inotropic responses induced by
      phenylephrine (10(-8) to 10(-4) M) and isoproterenol (10(-8) to 10(-4) M) were
      studied in rat left ventricular papillary muscles in vitro (in Krebs-Henseleit
      solution at 29 degrees C, pH 7.40, with 0.5 mM calcium and stimulation frequency
      at 12 pulses/min). The lusitropic effects were studied in isotonic (R1) and
      isometric (R2) conditions. RESULTS: One MAC halothane induced a negative
      inotropic effect (54 +/- 3%, P < 0.05), increased R1 (109 +/- 3%, P < 0.05), and
      decreased R2 (88 +/- 2%, P < 0.05). In control groups, phenylephrine (137 +/- 7%,
      P > 0.05) and isoproterenol (162 +/- 6%, P < 0.05) induced a positive inotropic
      effect. Halothane did not significantly modify the positive inotropic effect of
      calcium, suggesting that it did not modify the inotropic reserve of papillary
      muscles. In contrast, 1 MAC halothane enhanced the positive inotropic effects of
      phenylephrine (237 +/- 19%, P < 0.05) and isoproterenol (205 +/- 11%, P < 0.05).
      Halothane did not modify the lusitropic effect of phenylephrine under high or low
      load. In contrast, 1 MAC halothane impaired the positive lusitropic effect of
      isoproterenol under low load (P < 0.05), whereas it did not modify the positive
      lusitropic effect of isoproterenol under high load. CONCLUSIONS: At clinically
      relevant concentrations, halothane potentiated the positive inotropic effects of
      both alpha- and beta-adrenoceptor stimulation. Furthermore, halothane alters the
      positive lusitropic-effect of beta-adrenoceptor stimulation under low load.

PMID- 9009951
TI  - Role of renal cysteine conjugate beta-lyase in the mechanism of compound A
      nephrotoxicity in rats.
AB  - BACKGROUND: The sevoflurane degradation product compound A is nephrotoxic in
      rats, in which it undergoes extensive metabolism to glutathione and cysteine S
      conjugates. The mechanism of compound A nephrotoxicity in rats is unknown.
      Compound A nephrotoxicity has not been observed in humans. The authors tested the
      hypothesis that renal uptake of compound A S-conjugates and metabolism by renal
      cysteine conjugate beta-lyase mediate compound A nephrotoxicity in rats. METHODS:
      Compound A (0-0.3 mmol/kg in initial dose-response experiments and 0.2 mmol/kg in
      subsequent inhibitor experiments) was administered to Fischer 344 rats by
      intraperitoneal injection. Inhibitor experiments consisted of three groups:
      inhibitor (control), compound A, or inhibitor plus compound A. The inhibitors
      were probenecid (0.5 mmol/kg, repeated 10 h later), an inhibitor of renal organic
      anion transport and S-conjugate uptake; acivicin (10 mg/kg and 5 mg/kg 10 h
      later), an inhibitor of gamma-glutamyl transferase, an enzyme that cleaves
      glutathione conjugates to cysteine conjugates; and aminooxyacetic acid (0.5
      mmol/kg and 0.25 mmol/kg 10 h later), an inhibitor of renal cysteine conjugate
      beta-lyase. Urine was collected for 24 h and then the animals were killed.
      Nephrotoxicity was assessed by light microscopic examination and biochemical
      markers (serum urea nitrogen and creatinine concentration, urine volume and urine
      excretion of protein, glucose, and alpha-glutathione-S-transferase [alpha GST], a
      marker of tubular necrosis). RESULTS: Compound A caused dose-related
      nephrotoxicity, as shown by selective proximal tubular cell necrosis at the
      corticomedullary junction, diuresis, proteinuria, glucosuria, and increased alpha
      GST excretion. Probenecid pretreatment significantly (P < 0.05) diminished
      compound A-induced increases (mean +/- SE) in urine excretion of protein (45.5 +/
      3.8 mg/24 h vs. 25.9 +/- 1.7 mg/24 h), glucose (28.8 +/- 6.2 mg/24 h vs. 10.9 +/
      3.2 mg/24 h), and alpha GST (6.3 +/- 0.8 micrograms/24 h vs. 1.0 +/- 0.2
      microgram/24 h) and completely prevented proximal tubular cell necrosis.
      Aminooxyacetic acid pretreatment significantly diminished compound A-induced
      increases in urine volume (19.7 +/- 3.5 ml/24 h vs. 9.8 +/- 0.8 ml/24 h), protein
      excretion (37.2 +/- 2.7 mg/24 h vs. 22.2 +/- 1.8 mg/24 h), and alpha GST
      excretion (5.8 +/- 1.5 vs. 2.3 micrograms/24 h +/- 0.8 microgram/24 h) but did
      not significantly alter the histologic pattern of injury. In contrast, acivicin
      pretreatment increased the compound A-induced histologic and biochemical markers
      of injury. Compound A-related increases in urine fluoride excretion, reflecting
      compound A metabolism, were not substantially altered by any of the inhibitor
      treatments. CONCLUSIONS: Intraperitoneal compound A administration provides a
      satisfactory model of nephrotoxicity. Aminooxyacetic acid and probenecid
      significantly diminished histologic and biochemical evidence of compound A
      nephrotoxicity, whereas acivicin potentiated toxicity. These results suggest that
      renal uptake of compound A-glutathione or compound A-cysteine conjugates and
      cysteine conjugates metabolism by renal beta-lyase mediate, in part, compound A
      nephrotoxicity in rats.

PMID- 9009952
TI  - Bupivacaine preferentially blocks ventral root axons in rats.
AB  - BACKGROUND: Clinically, bupivacaine can provide excellent sensory anesthesia with
      minimal impairment of motor function. However, the mechanisms by which local
      anesthetics produce differential sensory-motor nerve block is still unknown. The
      primary site of action for spinal and epidural anesthetics is thought to be the
      intradural segment of the spinal root. To determine the differential
      susceptibility of single motor and sensory nerve fibers to local anesthetic
      conduction block, bupivacaine effects on individual dorsal root (DR) and ventral
      root (VR) axons were studied. METHODS: Lumbar DRs and VRs were excised from
      anesthetized adult male rats. Single-fiber dissection and recording techniques
      were used to isolate activity in individual axons. Supramaximal constant-voltage
      stimuli at 0.3 Hz were delivered to the root. During in vitro perfusion, each
      root was exposed to increasing concentrations of bupivacaine, and the minimum
      blocking concentration (C(m)) and the concentration that increased conduction
      latency by 50% (latency EC50) were measured. RESULTS: Ventral root axons were
      significantly more sensitive to the steady-state conduction blocking effects of
      bupivacaine than were either myelinated or unmyelinated DR axons (DR-C(m), 32.4
      microM; VR-C(m), 13.8 microM; P < 0.0001). In addition, VR axons were more
      susceptible to the latency-increasing effects of bupivacaine than were DR axons
      (DR-EC50 = 20.7 microM; VR-EC50 = 8.5 microM; P < 0.0001). Within axon groups,
      differential sensitivity as a function of conduction velocity (axon diameter), or
      length of nerve exposed to the anesthetic could not be demonstrated. CONCLUSIONS:
      In contrast to clinical expectations, low concentrations of bupivacaine
      preferentially block motor (VR) axons in the rat.

PMID- 9009953
TI  - Epidural and intrathecal n-butyl-p-aminobenzoate solution in the rat. Comparison
      with bupivacaine.
AB  - BACKGROUND: Epidural administration of an aqueous suspension of n-butyl-p
      aminobenzoate (BAB) to humans results in long-lasting sensory blockade without
      motor block. The dose-response of BAB administered epidurally and intrathecally
      as a solution was studied in rats to define the local anesthetic properties in an
      established animal model. METHODS: The time course of changes in tail withdrawal
      latency and motor function were determined in rats after epidural or intrathecal
      administration of solutions of BAB or bupivacaine. The dose-response relation was
      determined and median effective dose values were calculated. RESULTS: After
      epidural and intrathecal administration of BAB solutions, the onset and duration
      of the antinociceptive action were comparable to bupivacaine. Median effective
      dose values for tail-withdrawal latency of 6 s or more were significantly greater
      for BAB. After both routes of administration, BAB clearly affected motor
      function. CONCLUSIONS: When administered epidurally and intrathecally as a
      solution, BAB is a local anesthetic of relative low potency with onset and
      duration of action comparable to those of bupivacaine. These findings suggest
      that the long-lasting action obtained after applying BAB suspension results from
      the slow dissolution (continuous release) of the solid BAB deposited in the
      epidural space.

PMID- 9009954
TI  - Halothane, isoflurane, and sevoflurane reduce postischemic adhesion of
      neutrophils in the coronary system.
AB  - BACKGROUND: Polymorphonuclear neutrophils (PMNs) contribute to postischemic
      reperfusion damage in many organs and tissues, a prerequisite being adhesion of
      PMNs to vascular endothelial cells. Because adhesion processes involve orderly
      interactions of membrane proteins, it appeared possible that "membrane effects"
      of volatile anesthetics could interfere. We investigated the effects of
      halothane, isoflurane, and sevoflurane on postischemic adhesion of human PMNs in
      the intact coronary system of isolated perfused guinea pig hearts. METHODS: The
      hearts (n = 7-10 per group) were perfused in the "Langendorff" mode under
      conditions of constant flow (5 ml/min) using modified Krebs-Henseleit buffer
      equilibrated with 94.4% oxygen and 5.6% carbon dioxide. Global myocardial
      ischemia was induced by interrupting perfusion for 15 min. In the second minute
      of reperfusion (5 ml/min), a bolus dose of 6 x 10(5) PMNs was injected into the
      coronary system. The number of cells reemerging in the coronary effluent was
      expressed as a percentage of the total number of applied PMNs. Halothane,
      isoflurane, and sevoflurane, each at 1 and 2 minimal alveolar concentration
      (MAC), were vaporized in the gas mixture and applied from 14 min before ischemia
      until the end of the experiment. RESULTS: Under nonischemic conditions, 24.7 +/-
      1.3% of the injected neutrophils did not reemerge from the perfused coronary
      system. Subjecting the hearts to global ischemia augmented retention (36.4 +/-
      2.8%, P < .05). Application of halothane reduced adhesion of neutrophils to 22.6
      +/- 2.1% and 24.2 +/- 1.8% at 1 and 2 MAC, respectively (P < .05). Exposure to 1
      and 2 MAC isoflurane was similarly effective, whereas basal adhesion was not
      significantly influenced. Sevoflurane-treated hearts (1 and 2 MAC) also showed
      decreased adhesion of PMNs (23 +/- 2.3% and 24.8 +/- 1.8%, respectively; P < .05)
      and an identical reduction resulted when sevoflurane (1 MAC) was applied only
      with the onset of reperfusion. CONCLUSIONS: Although the mechanism of action of
      volatile anesthetics remains unclear in these preliminary studies, their
      inhibitory effect on ischemia-induced adhesion of PMNs may be beneficial for the
      heart during general anesthesia.

PMID- 9009955
TI  - Synergistic antinociceptive interactions of morphine and clonidine in rats with
      nerve-ligation injury.
AB  - BACKGROUND: Ligation injury of the L5/L6 nerve roots in rats produces behavioral
      signs representative of clinical conditions of neuropathic pain, including
      tactile allodynia and thermal and mechanical hyperalgesia. In this model,
      intrathecal morphine shows no antiallodynic activity, as well as decreased
      antinociceptive potency and efficacy. This study was designed to explore the
      antinociceptive activity of intrathecal clonidine alone or in combination with
      intrathecal morphine (1:3 fixed ratio) in nerve-injured rats. The aims, with this
      study, were to use nerve-injured animals to determine: (1) whether the
      antinociceptive potency and efficacy of intrathecal clonidine was altered, and
      (2) whether the combination of intrathecal morphine and clonidine would act
      synergistically to produce antinociception. METHODS: Unilateral nerve injury was
      produced by ligation of the L5 and L6 spinal roots of male Sprague-Dawley rats.
      Sham-operated rats underwent a similar surgical procedure but without nerve
      ligation. Morphine and clonidine were given intrathecally through implanted
      catheters alone or in a 1:3 fixed ratio. Nociceptive responses were measured by
      recording tail withdrawal latency from a 55 degrees C water bath, and data were
      calculated as % maximal possible effect (%MPE). RESULTS: Morphine produced a dose
      dependent antinociceptive effect in both sham-operated and nerve-injured rats.
      The doses calculated to produce a 50 %MPE (i.e., A50) (+/-95% confidence
      intervals [CI]) were 15 +/- 4.9 micrograms and 30 +/- 18 micrograms,
      respectively. Though morphine was able to produce a maximal response (100%) in
      sham-operated rats, the maximal response achieved in nerve-injured animals was
      only 69 +/- 21.9 %MPE. Clonidine produced a dose-dependent effect, with an A50
      (+/-95% CI) of 120 +/- 24 micrograms in sham-operated rats. In nerve-ligated
      rats, clonidine produced a maximal effect that reached a plateau of 55 +/- 10.9
      %MPE and 49 +/- 10.2 %MPE at 100 and 200 micrograms, respectively, preventing the
      calculation of an A50. In sham-operated rats, a morphine-clonidine mixture
      produced maximal efficacy, with an A50 (+/-95% CI) of 15 +/- 9.2 micrograms
      (total dose), significantly less than the theoretical additive A50 of 44 +/- 10
      micrograms. In L5/L6 nerve-ligated rats, the morphine-clonidine combination
      produced maximal efficacy, with an A50 (+/-95% CI) of 11 +/- 5.4 micrograms
      (total dose), which was significantly less than the theoretical additive A50 of
      118 +/- 73 micrograms, indicating a synergistic antinociceptive interaction. The
      intrathecal injection of [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO) produced A50
      values of 0.23 microgram (range, 0.09-0.6) and 0.97 microgram (range, 0.34-2.7)
      in sham-operated and ligated rats, respectively. Phentolamine (4 mg/kg,
      intraperitoneally) produced no antinociceptive effect alone and attenuated,
      rather than enhanced, the effect of morphine in both groups of rats. CONCLUSIONS:
      These data show that: (1) clonidine, like morphine, loses antinociceptive potency
      and efficacy after nerve ligation injury, and (2) strongly suggest that a spinal
      combination of morphine and clonidine synergize under conditions of nerve injury
      to elicit a significant antinociceptive action when either drug alone may be
      lacking in efficacy. It is unlikely that the synergy of morphine with clonidine
      is due to an attenuation of spinal sympathetic outflow by clonidine, because the
      sympatholytic agent phentolamine produced an opposing effect on morphine
      antinociception. The data suggest that combinations of morphine and clonidine may
      prove useful in controlling pain in patients with neuropathic conditions.

PMID- 9009956
TI  - In vitro effects of dantrolene on rat myocardium.
AB  - BACKGROUND: Dantrolene is the only known effective treatment for malignant
      hyperthermia. However, its effects on myocardial contraction and relaxation
      remain debatable. METHODS: The effects of dantrolene (10(-5)-10(-3) M) on the
      contractility of rat left ventricular papillary muscles were investigated in
      vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, 2.5 and 0.5 mM Ca2+,
      stimulation frequency 12 pulses/min). The authors studied contraction,
      relaxation, contraction-relaxation coupling under high and low load, energetics,
      and postrest potentiation. The effects of dantrolene after depletion of
      catecholamine stores with reserpine also were studied. RESULTS: Dantrolene
      induced a moderate concentration-dependent negative inotropic effect at a low
      calcium concentration (active force at 10(-4) M: 86 +/- 14% of control values, P
      < 0.05), but not at a high calcium concentration. Dantrolene did not
      significantly modify the curvature of the force-velocity relation, suggesting
      that it did not modify myocardial energetics. Dantrolene induced no significant
      lusitropic effect under low load, suggesting that it did not modify calcium
      uptake by the sarcoplasmic reticulum. Dantrolene did not significantly modify
      postrest potentiation and postrest potentiation recovery, suggesting that it did
      not modify maximum capacity of calcium release by the sarcoplasmic reticulum nor
      its postrest resetting capacity. Reserpine did not modify the myocardial effects
      of dantrolene. CONCLUSIONS: In rat myocardium, dantrolene did not modify any of
      the sarcoplasmic reticulum functions tested (uptake, release, postrest recovery).
      Dantrolene induced a moderate negative inotropic effect, probably mediated by a
      decrease in transarcolemmal calcium entry, and this negative inotropic effect was
      blunted by an increase in calcium concentration.

PMID- 9009957
TI  - Neural blockade for diagnosis and prognosis. A review.
AB  - On the basis of the published material reviewed above, we conclude that there are
      many limitations that weaken the theoretic basis for neural blockade as a
      diagnostic or prognostic tool. In addition, these procedures in general lack
      thorough documentation of clinical usefulness. Reasonable employment of
      diagnostic neural blockade, therefore, requires not only care in technique and
      confirmation of effects, but also caution in interpretation and application of
      the results. This critical evaluation needs to be tempered, however, by two
      further observations. Experienced and observant clinicians have found these
      procedures may, on certain occasions, provide information that is helpful in
      guiding subsequent therapy, so we should not be in haste to dismiss the
      accumulated judgment of practitioners. Finally, the confusion and complexity that
      typifies diagnosis in chronic pain may justify the selective use of diagnostic
      blocks that make anatomic and physiologic sense, even if their validity is
      incompletely proved.

PMID- 9009958
TI  - Local anesthesia in posterior cervical surgery.

PMID- 9009959
TI  - Ruptured aortic aneurysm and cardiac arrest associated with spinal anesthesia.

PMID- 9009960
TI  - Apparent failure of a precordial magnet and pacemaker programmer to convert a DDD
      pacemaker to VOO mode during the use of the electrosurgical unit.

PMID- 9009961
TI  - Asystole and severe bradycardia during epidural anesthesia in orthopedic
      patients.

PMID- 9009962
TI  - Perioperative autologous transfusion service: a logical extension of our role in
      the operating room.

PMID- 9009963
TI  - Anesthesia preoperative evaluation clinic.

PMID- 9009964
TI  - Anesthesia preoperative evaluation clinic.

PMID- 9009965
TI  - Anesthesia preoperative evaluation clinic.

PMID- 9009966
TI  - Anesthesia preoperative evaluation clinic.

PMID- 9009967
TI  - Interaction between nondepolarizing muscle relaxants.

PMID- 9009968
TI  - Transesophageal atrial pacing as a trigger for intraaortic balloon pumping.

PMID- 9009969
TI  - Is pentobarbital analgesic in the rat formalin test?

PMID- 9009970
TI  - Health information on the Internet. Opportunities and pitfalls.

PMID- 9009971
TI  - Dose of exercise and health benefits.

PMID- 9009972
TI  - The German health system. Lessons for reform in the United States.

PMID- 9009973
TI  - Diagnostic dilemmas in polymyalgia rheumatica.
AB  - Polymyalgia rheumatica is a clinical syndrome of proximal muscle pain in older
      patients that often presents a diagnostic challenge because of the large
      differential diagnosis, lack of definitive diagnostic criteria, and relatively
      frequent "atypical" clinical findings, such as peripheral synovitis, distal
      extremity pain, normal erythrocyte sedimentation rate, and mild weakness. Despite
      an extensive differential diagnosis that includes endocarditis and steroid
      responsive malignant neoplasms, routine laboratory testing should be limited, and
      a low-dose corticosteroid trial is useful as the final step in the evaluation.
      The clinical overlap with seronegative rheumatoid arthritis is striking,
      suggesting that these diagnoses may represent different presentations of a
      similar disease process. While concurrent asymptomatic temporal arteritis is
      common, there are no data to support obtaining a temporal artery biopsy in
      patients with pure polymyalgia rheumatica symptoms.

PMID- 9009974
TI  - Nutritional management of cardiovascular risk factors. A randomized clinical
      trial.
AB  - BACKGROUND: Adherence to dietary recommendations for disease management is often
      hindered by the complexity of incorporating them into the daily diet. Nutrition
      and cardiovascular scientists and food technologists collaborated to develop a
      prepared meal plan that meets national dietary guidelines for cardiovascular risk
      reduction. OBJECTIVE: To assess the clinical effects of this plan, which
      incorporates all National Academy of Sciences National Research Council
      recommended dietary allowances for vitamins, minerals, and macronutrients,
      compared with a patient-selected American Heart Association Step I and Step II
      diet plan. METHODS: This multicenter, randomized, parallel-intervention trial was
      conducted at 10 medical centers in the United States and Canada and involved 560
      men and women with hypertension, dyslipidemia, or diabetes. Following calculation
      of prescriptions to meet individual nutritional requirements based on the Harris
      Benedict equation, participants were randomized to the Campbell's Center for
      Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast,
      lunch, and dinner meals provided to participants, or a nutritionist-guided
      American Heart Association Step I and Step II diet, in which participants self
      selected foods to meet their nutrition prescription for 10 weeks. MAIN OUTCOME
      MEASURES: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c),
      and insulin levels; body weight; dietary intake; and quality of life. RESULTS:
      Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life
      (P < or = .001 for all findings except low-density lipoprotein-high-density
      lipoprotein ratio, P = .25) all improved on both nutrition plans. Mean
      differences (+/-SD) between baseline and treatment clinical values for the CCNW
      and the self-selected diet groups (between-group P values), respectively, were as
      follows: systolic BP, -6.4 +/- 9.2 mm Hg and -4.6 +/- 9.0 mm Hg (P = .02);
      diastolic BP, -4.2 +/- 5.7 mm Hg and -3.0 +/- 5.1 mm Hg (P = .006); cholesterol, 
      0.32 +/- 0.58 mmol/L and -0.27 +/- 0.56 mmol/L (-12.4 +/- 22.5 mg/dL and -10.4 +/
      21.9 mg/dL) (P = .30); glucose, -0.65 +/- 1.88 mmol/L and -0.75 +/- 2.03 mmol/L
      (-11.7 +/- 34.0 mg/dL and -13.5 +/- 36.6 mg/dL) (P = .10); and HbA1c, -0.4% +/-
      0.8% and -0.3% +/- 0.7% (P = .66). Weight loss with the CCNW and self-selected
      plans, respectively, was as follows: men, -4.5 +/- 3.6 kg and -3.5 +/- 3.3 kg;
      and women, -4.8 +/- 3.0 kg and -2.8 +/- 2.8 kg. Quality of life was significantly
      improved for daily and work activities (P < .05) and nutritional health
      perceptions (P < .05) with the CCNW plan relative to the self-selected group.
      Overall nutrient intake and compliance were both significantly (P < .001) better
      with the CCNW plan. CONCLUSIONS: Nutritionally balanced meals that meet the
      recommendations of national health organizations improved multiple risk factors
      for patients with cardiovascular disease. The CCNW plan resulted in greater
      clinical benefits, nutritional completeness, and compliance than the self
      selected diet. The CCNW is a comprehensive nutrition plan, convenient for both
      prescription and practice, and appears viable for effecting favorable dietary
      changes in patients at high risk for cardiovascular disease.

PMID- 9009975
TI  - Cardiovascular events and correlates in the Veterans Affairs Diabetes Feasibility
      Trial. Veterans Affairs Cooperative Study on Glycemic Control and Complications
      in Type II Diabetes.
AB  - BACKGROUND: The risks and benefits of intensive therapy in non-insulin-dependent
      diabetes mellitus (NIDDM) need to be defined. In preparation for a long-term
      trial, a feasibility study of 153 men in 5 medical centers compared standard vs
      intensive insulin therapy. OBJECTIVE: To assess the rate of development of new
      cardiovascular events and their correlates. METHODS: Patients with a mean +/- SD
      age of 60 +/- 6 years and diagnosis of NIDDM for 7.8 +/- 4.0 years were randomly
      assigned to a standard (1 insulin injection every morning) or to an intensive
      treatment arm (stepped plan from 1 evening injection of insulin, alone or with
      glipizide, to multiple daily injections) designed to attain near-normal glycemia
      levels. A 2.07% separation of glycosylated hemoglobin (HbA1c) was sustained for a
      mean follow-up of 27 months (P < .001). Predefined cardiovascular events were
      assessed by a committee unaware of treatment assignment. RESULTS: Mild and
      moderate hypoglycemic events were more frequent in the intensive than in the
      standard treatment arm (16.5 vs 1.5 per patient per year, respectively). Mean
      insulin dose was 23% lower in the standard treatment arm (P < .001). There were
      61 new cardiovascular events in 24 patients (32%) in the intensive treatment arm
      and in 16 patients (20%) in the standard treatment arm (P = .10). There was no
      difference in total and cardiovascular mortality (n = 5 and n = 3 in the
      intensive and standard treatment arms, respectively) or in new events in patients
      with cardiovascular history (n = 10 in each arm). In Cox regression analysis, the
      only significant correlate for new cardiovascular events was previous
      cardiovascular disease (P = .04). Entering in the analysis any baseline
      cardiovascular abnormality, the regression model indicated a lower HbA1c level
      prior to the event as the only correlate for new cardiovascular events (P = .05).
      CONCLUSION: A long-term prospective trial is needed to assess the risk-benefit
      ratio of intensive insulin therapy for NIDDM in patients who require it.

PMID- 9009977
TI  - Risk factors for sporadic infection with Escherichia coli O157:H7.
AB  - BACKGROUND: Little is known about risk factors for sporadic infection with
      Escherichia coli O157:H7. In response to a sharp increase in reported cases in
      New Jersey during July 1994, we conducted a case-control study to identify
      principal sources of infection and contributing practices. METHODS: Standardized
      questionnaires were used to evaluate (1) potential exposures of case patients and
      matched controls and (2) knowledge, attitudes, and practices of food preparers in
      case and control households. Patient isolates were subtyped by pulsed-field gel
      electrophoresis. RESULTS: Patients with E coli O157:H7 infection (N = 23; median
      age, 9 years; 55% female) were more likely than healthy controls to have eaten a
      hamburger in the week preceding illness (matched odds ratio, undefined; P <
      .001); 80% of the hamburgers eaten by ill persons were prepared at home. Food
      preparers in case households were less likely than those in control households to
      report washing their hands (odds ratio, 8.5; P < .005) and work surfaces (odds
      ratio, 10.5; P < .05) after handling raw ground beef. Pulsed-field gel
      electrophoresis yielded 17 unique subtypes among the 23 patient isolates,
      indicating multiple sources of infection. CONCLUSIONS: Hamburgers prepared at
      home are an important source of sporadic E coli O157:H7 infections. We estimate
      that adequate hand washing by food preparers could have prevented 34% of E coli
      O157:H7 infections in the study population.

PMID- 9009976
TI  - Relationship of distance run per week to coronary heart disease risk factors in
      8283 male runners. The National Runners' Health Study.
AB  - BACKGROUND: Official guidelines from the Centers for Disease Control and
      Prevention and the American College of Sports Medicine state that every adult
      should accumulate 30 minutes or more of moderate-intensity physical activity on
      most, preferably all, days of the week. OBJECTIVE: To examine the dose-response
      relationship between coronary heart disease (CHD) risk factors and vigorous
      exercise above the recommended minimum levels to assess whether further benefits
      accrue. METHODS: Physician-supplied medical data were compared with reported
      distance run in a national cross-sectional survey of 8283 male recreational
      runners. RESULTS: Compared with runners who ran less than 16 km (10 miles) per
      week, long-distance runners (> or = 80 km/wk) showed an 85% reduced prevalence of
      high-density lipoprotein cholesterol levels that were clinically low (< 0.9
      mmol/L [< 35 mg/dL]), a 2.5-fold increased prevalence of clinically defined high
      levels of high-density lipoprotein cholesterol (ie, > or = 1.55 mmol/L [> or = 60
      mg/dL], the level thought to be protective against CHD), a nearly 50% reduction
      in hypertension, and more than a 50% reduction in the use of medications to lower
      blood pressure and plasma cholesterol levels. Estimated age-adjusted 10-year CHD
      risk was 30% lower in runners who averaged more than 64 km/wk than in those who
      averaged less than 16 km/wk (42 vs 61 events per 1000 men). Each 16-km
      incremental increase in weekly distance run up to 64 to 79 km/wk was associated
      with significant increases in high-density lipoprotein cholesterol levels and
      significant decreases in adiposity, triglyceride levels, the ratio of total
      cholesterol to high-density lipoprotein cholesterol level, and estimated CHD
      risk. CONCLUSIONS: Our data (1) suggest that substantial health benefits occur at
      exercise levels that exceed current minimum guidelines and (2) do not exhibit a
      point of diminishing return to the health benefits of running at any distance
      less than 80 km/wk.

PMID- 9009978
TI  - Requests for medical advice from patients and families to health care providers
      who publish on the World Wide Web.
AB  - BACKGROUND: The Internet is a novel, rapidly growing means of worldwide public
      communication. METHODS: We reviewed all unsolicited electronic mail and other
      communications from nonmedical individuals requesting medical information over a
      12-month period from the physician at 1 established site on the World Wide Web.
      This site was the only Internet site with a primary focus on cardiac arrhythmias.
      RESULTS: Seventy unsolicited inquiries were received from 39 patients and 20
      family members (the sources of 11 inquiries are unknown) from 20 states,
      Washington, DC, and 9 foreign countries (locations of 15 inquiries are unknown).
      Follow-up was obtained in 22 cases. The inquiries concerned cardiological
      conditions in 67 cases (96%) and cardiac electrophysiologic conditions and
      procedures in 52 cases (74%). The goals of the inquiries were diagnosis (15),
      therapy (48), prognosis (1), and patient education (6). On follow-up of 22 cases,
      the people initiating the inquiries stated that they were reassured (16),
      consulted a general cardiologist (1), consulted a cardiac electrophysiologist
      (4), or visited a tertiary care electrophysiology center (1). CONCLUSIONS: The
      increasing use of the Internet by the general public seeking specific medical
      information for themselves and for their families suggests a widespread, unmet
      need for objective medical advice. This study demonstrates that the public can
      choose accurately whom to ask for subspecialty advice in the area of
      cardiovascular diseases. Professional societies and regulatory agencies should
      develop physician guidelines for providing medical advice over the Internet.

PMID- 9009979
TI  - Group B streptococcus bacteremia in nonpregnant adults.
AB  - BACKGROUND: We report the largest series of group B streptococcal (GBS)
      bacteremia cases reported at a single institution. METHODS: During a 10-year
      period (1985-1994), 90 GBS bacteremia cases (0.95% of significant bacteremic
      episodes) were detected. We describe the 51 episodes that occurred in nonpregnant
      adults for which enough clinical and microbiological information is available.
      RESULTS: Incidence of GBS has significantly increased during the study period
      (from 0.08 per 1000 admissions in 1985 to 0.3 per 1000 in 1994). Mean age of
      patients was 63.3 years (range, 21-88 years) and 53% were men. The most common
      underlying conditions were liver diseases (35.3%), malignancies (33.3%), and
      diabetes mellitus (27.5%). Only 2 patients did not have any underlying condition
      and no patient with the human immunodeficiency virus had GBS bacteremia in our
      series. The origins of the episodes of bacteremia were as follows: primary
      bacteremia (39.2%), skin and soft tissue infections (15.7%), urinary tract
      infections (11.8%), pneumonia (9.8%), peritonitis (9.8%), catheter infection
      (5.9%), postendoscopic bacteremia (5.9%), and endocarditis (2%). All isolates
      were susceptible to penicillin G potassium, ampicillin sodium, cephalothin
      sodium, cefotaxime sodium, and vancomycin hydrochloride. One ciprofloxacin
      hydrochloride-resistant strain was discovered and resistance to erythromycin
      stearate increased from 8% in 1992 to 18% in 1994. The overall mortality rate was
      33.3% and deaths were considered related to the GBS bacteremia in 25.5% of the
      cases. Factors for poor prognosis were central nervous system diseases,
      alcoholism, shock, renal failure, and consciousness impairment. CONCLUSIONS:
      Group B streptococcus is a rising cause of bacteremia in elderly patients with
      severe underlying conditions. It conveys high morbidity and mortality rates.
      Macrolides should not be used empirically for treatment of patients with
      penicillin allergies.

PMID- 9009980
TI  - Sodium concentration of water from softeners.
AB  - OBJECTIVES: To determine whether water is safe for consumption after it has
      passed through a water softener and whether there are any health and
      environmental implications of cationic water softeners. METHODS: Sodium
      concentration was measured in 59 water samples that had passed through a water
      softener and was compared with the sodium concentration of 5 samples from 4
      different local municipal sources. RESULTS: The mean +/- SD sodium concentration
      of softened well water was 278 +/- 186 mg/L (range, 46-1219 mg/L). There were 10
      (17%) households with sodium levels greater than 400 mg/L. The mean +/- SD sodium
      concentration of municipal, nonsoftened water was 110 +/- 98 mg/L (range, 0-253
      mg/L). CONCLUSIONS: Softened well water in our area on average contained a 2.5
      times-higher concentration of sodium than local municipal water, comparable with
      previous reports. It is unlikely that the increased sodium from softened water
      would have any health risks for most people. This may not be true for people on
      severely sodium-restricted diets.

PMID- 9009981
TI  - Glycine-induced hypo-osmolar hyponatremia.
AB  - BACKGROUND: Hyponatremia is commonly observed following transurethral resection
      of the prostate or endometrial resection when the operative field is irrigated
      with hypotonic glycine. Although glycine-induced hyponatremia has been associated
      with brain damage, the mortality is low, and it has been suggested that the
      condition might not be hypo-osmolar and thus might not cause brain edema.
      OBJECTIVE: To determine if glycine-induced hyponatremia is a hypo-osmolar
      condition. METHODS: The study was a retrospective evaluation of 13 men who
      underwent transurethral resection of the prostate and 5 women who underwent
      transcervical endometrial resection at 2 university medical centers. In all
      patients, hypotonic glycine (200 mmol/L) was the irrigating solution.
      Measurements were made of the plasma sodium, osmolality, glucose, urea, glycine,
      and ammonia; and arterial pH, PO2 and PCO2. Mortality and the occurrence of
      respiratory arrest were recorded. Data are given as mean (+/- SE). RESULTS: The
      plasma sodium in 18 patients was 106 +/- 2 mmol/L and the measured osmolality was
      235 +/- 5 mOsm/kg H2O. Glycine was measured as the difference between measured
      and calculated plasma osmolality and was 18 +/- 2 mmol/L. Four patients suffered
      respiratory arrest; all died. One patient had elevated blood ammonia (130
      mumol/L) with a plasma sodium level of 110 mmol/L. She was treated with
      endotracheal intubation and respiratory support plus hypertonic sodium chloride,
      and recovered. The other 14 surviving patients were treated with hypertonic
      sodium chloride. CONCLUSIONS: Patients who undergo transurethral resection of the
      prostate or endometrial resection with hypotonic glycine as the irrigating medium
      can experience symptomatic hyponatremia that is hypo-osmolar and can be fatal.
      Therapy with hypertonic sodium chloride was associated with survival in 14 of 14
      patients. Ammonia intoxication also can develop, and can be managed with
      respiratory support.

PMID- 9009982
TI  - Relapse of tuberculosis after treatment in human immunodeficiency virus-infected
      patients.
AB  - OBJECTIVES: To evaluate the relapse rate of tuberculosis after a complete course
      of antituberculous therapy in human immunodeficiency virus-infected patients and
      to identify the risk factors for relapse. PATIENTS AND METHODS: Historic cohort
      study of all adult patients who were diagnosed as having human immunodeficiency
      virus infection and a first episode of culture-proved tuberculosis at 2
      university hospitals in Madrid, Spain, between 1986 and 1992, and who completed
      at least 6 months of treatment were included and followed up until September
      1994. RESULTS: Of 276 patients with human immunodeficiency virus infection and
      tuberculosis, 87 could not be evaluated (6 died before treatment, 39 died during
      treatment, 36 did not complete the planned therapy, and 6 were unavailable during
      treatment). The remaining 189 received a standard regimen (ie, 3 or 4 drugs,
      always including rifampin and isoniazid, for > or = 6 months). The median
      duration of follow-up for these 189 patients was 31.5 months, with a total of
      4668 patient-months of follow-up after treatment; 105 patients (56%) were
      followed up until death. The relapse rate was 7.9% (2.7/100 patient-years). With
      multivariate analysis, a shorter duration of treatment and a low CD4+ cell count
      were associated with a greater probability of relapse. Relapses occurred in 5
      (3.4%) of 148 patients who were treated for 9 or more months (1.7/100 patient
      years) and in 10 (24%) of 41 patients who were treated for less than 9 months
      (10.9/100 patient-years) (P < .001; relative hazard, 9.2; 95% confidence
      interval, 3.1-26.9). CONCLUSIONS: As standard antituberculous therapy for 9
      months is associated with a low rate of relapse, maintenance therapy is not
      required. Duration of treatment for less than 9 months is associated with a high
      rate of relapse.

PMID- 9009983
TI  - Association between blood pressure and dietary factors in the dietary and
      nutritional survey of British adults.
AB  - OBJECTIVES: To measure the associations among blood pressure, hypertension, and
      recorded dietary factors. METHODS: Data were analyzed from the computer file of
      the Dietary and Nutritional Survey of British Adults, in which persons of both
      sexes aged 16 to 64 years living in private households (excluding pregnant women)
      had been randomly selected from the United Kingdom Electoral Register. Main
      outcome measures were systolic blood pressure, diastolic blood pressure, and
      hypertension (defined as systolic blood pressure of > or = 140 mm Hg, diastolic
      blood pressure of > or = 90 mm Hg, or both, or receiving antihypertensive
      medication). RESULTS: After controlling for 24-hour urinary potassium excretion,
      age, obesity, alcohol intake, and season of interview, a single measure of 24
      hour urinary sodium excretion was significantly associated with systolic blood
      pressure (P < or = .001), diastolic blood pressure (P < .05), and hypertension (P
      = .009). These associations persisted after controlling for many variables of
      blood chemistry and dietary intake. CONCLUSIONS: Sodium is positively associated
      with blood pressure over a range of sodium excretion rates from 70 to 400 mmol/d.
      This finding supports the international consensus that the risk of hypertension
      is lower when salt intake is lower and suggests that a proportion of the British
      population has a sodium excretion rate that is habitually low enough to have some
      preventive effect.

PMID- 9009984
TI  - Parkinsonism associated with long-term cocaine abuse.

PMID- 9009985
TI  - Alcoholism in the elderly.

PMID- 9009986
TI  - Caffeine as a stimulant against suicide.

PMID- 9009987
TI  - Atheroembolism or cholesterol crystal embolization.

PMID- 9009988
TI  - A standardized diet for performing focal fat excretion studies.

PMID- 9009989
TI  - Increasing the stability of unstable angina.

PMID- 9009990
TI  - Vestibulospinal, reticulospinal and descending propriospinal nerve fibres in man.
AB  - The course and location of vestibulospinal, reticulospinal and descending
      propriospinal fibres in man are reported. The investigation was carried out on
      three patients with supraspinal lesions, four with transection of the spinal cord
      and 33 with anterolateral cordotomies. The lateral vestibulospinal tract at the
      medullospinal junction and in the first three cervical segments lies on the
      periphery of the spinal cord lateral to the anterior roots. It moves to the
      sulcomarginal angle in the remaining cervical segments. In the thoracic cord, it
      moves laterally, being traversed by the most lateral of the anterior roots.
      Reticulospinal fibres descend bilaterally in the spinal cord with a preponderance
      of ipsilateral fibres. Reticulospinal fibres in general do not form well-defined
      tracts, but are scattered throughout the anterior and lateral columns. They are
      intermingled with propriospinal fibres and with ascending and descending fibres
      of other systems. Most reticulospinal fibres move posterolaterally as they
      descend. It follows that fibres from the brainstem that enter the cord in the
      anterior column may be in the lateral column anterior to the lateral
      corticospinal tract at lower levels. Reticulospinal fibres within the lateral
      column lie anterior to the lateral corticospinal tract. They consist of scattered
      fibres between the lateral horn and the periphery, most of them in the medial two
      thirds of the column. In addition, they are present in a more compact group,
      forming a triangle on transverse section on the periphery of the lateral column,
      immediately anterior to the lateral corticospinal tract. On the periphery of the
      anterior and anterolateral columns reticulospinal fibres descend as small groups
      or as a continuous band of fibres. The most medial of these reaches the sacral
      segments and is included in the sulcomarginal fasciculus. A compact group of
      fibres, shown previously to be central sympathetic fibres ending in the
      intermediolateral and intermediomedial cell columns, surrounds the lateral horn.
      They do not extend throughout the thoracic cord in all cases. Anterior to this
      group is another group of fibres lying on the anterolateral surface of the
      anterior horn. As these fibres were degenerating following a pontine lesion, they
      must be reticulospinal fibres. The fibres were not seen in all cases and they did
      not always reach the lowest thoracic segments. Reticulospinal fibres enter the
      grey matter in the zona intermedia and along the anterolateral and anterior
      surfaces of the anterior horns. Caudal to the cervical enlargement, the number of
      reticulospinal fibres decreases, and their place is taken by propriospinal
      fibres. But they are not totally replaced by the propriospinal fibres, for
      reticulospinal fibres continue down into the lowest sacral segments. Of the
      propriospinal fibres, the majority are short: descending fibres within the
      juxtagriseal layer are one to two segments long or less.

PMID- 9009991
TI  - A clinical and neurophysiological study of a patient with an extensive
      transection of the spinal cord sparing only a part of one anterolateral quadrant.
AB  - In 1976, Noordenbos and Wall studied sensory functions in a woman with a
      surgically verified T3 spinal cord transection which spared only a part of the
      left anterolateral quadrant, We re-investigated this unique case 18 years after
      the lesion and included a comparable sensory examination, MRI of the spinal cord,
      somatosensory evoked potentials, PET-activation study during hand and foot
      vibration and analysis of flexion reflex modulation during the Jendrassik
      manoeuvre. Our results show that the residual anterolateral quadrant contains
      ascending pathways carrying a wide range of sensory information as well as
      descending pathways modulating flexion reflex activity at the spinal level.
      Moreover, the changes in sensory functions and the unique pattern of cortical
      activation suggest a functional reorganization of the connectivity between the
      periphery and the cerebral cortex. Changes of facilitation and/or of inhibition
      at different levels of the somatosensory system may account for these longterm
      plastic changes.

PMID- 9009992
TI  - Motor recovery after stroke. Morphological and functional brain alterations.
AB  - The aim of this study was to evaluate the relationships of morphological and CBF
      patterns with both the severity and the evolution of the motor deficit in the
      late phase of stroke and, in particular, to identify morphological and/or
      functional brain alterations associated with a persistent severe motor deficit or
      a poor, delayed motor recovery. We analysed CT/MRI and single photon emission
      tomography (SPET) findings from 37 patients studied in the chronic phase of
      stroke (mean duration +/- SD = 3.6 +/- 1.6 months), whom we were able to follow
      clinically for a period of 3 months. The eventual degree of motor recovery
      correlated significantly (negatively) with the time since stroke at entry, but
      not with the severity of neurological impairment at entry. The volume, side and
      location (cortical or subcortical) of the infarct did not correlate with either
      the severity or the evolution of the motor deficit. Patients with a CT/MRI lesion
      of the parietal lobe (n = 8) showed a more severe motor deficit than those with
      other cortical locations. The severity of the motor deficit correlated
      significantly (negatively) with CBF values in the supplementary motor area (SMA)
      and parietal areas of the damaged hemisphere, and in the contralateral undamaged
      primary motor cortex. The degree of motor improvement correlated significantly
      (positively) with CBF values in the contralateral undamaged thalamus, lentiform
      and caudate nuclei, and premotor cortex. In the late phase of stroke, the
      severity of the motor deficit may be positively associated with the functional
      impairment of associative parietal and frontal areas of the damaged hemisphere.
      The functional impairment of the basal ganglia-frontal network in the undamaged
      hemisphere seems to be related to a poor, delayed motor recovery.

PMID- 9009993
TI  - Split cervical spinal cord with Klippel-Feil syndrome: seven cases.
AB  - We report seven cases of rare high cervical split spinal cord associated with
      extensive vertebral fusions (Klippel-Feil anomaly). In light of previous
      embryological theories and recent research findings we attempt to explain the
      origin of split cord and vertebral fusions. Two distinctly separate mechanisms
      are suggested for the development of split cords observed in our cases: a midline
      lesion bisecting the neuroepithelium and the notochordal plate could be
      responsible for complete splitting of the cervical cord with anterior bony defect
      while a localized disturbance of cervical neural tube closure would account for
      cases with partial dorsal splitting of the cord with posterior vertebral defect.
      Vertebral fusion anomalies are likely to be associated with disturbance of Pax-1
      gene expression in the developing vertebral column. We confirm with our cases the
      frequent association of failure of normal segmentation and split cord in the
      cervical region. Clinically, only three patients had neurological deficit which
      was mild and has remained stable, and they had no radiological evidence of
      tethering; the minimal disproportionate growth of the cord and spine and the
      rarity of a bony spur in the cervical region are the likely reasons. A
      conservative policy was therefore pursued in these cases with careful long-term
      follow-up.

PMID- 9009994
TI  - Thalamic haemorrhage.
AB  - Thalamic haemorrhage is usually considered a single entity although the thalamus
      is composed of anatomically as well as functionally discrete subregions receiving
      blood from different arteries. The clinical features vary according to the
      intrathalamic location of the haematomas and the bleeding artery. We investigated
      the impact of haematoma location and vascular territory on the clinical symptoms
      and signs, neuro-imaging findings and clinical courses of patients with thalamic
      haemorrhages by a retrospective analysis of 175 consecutive patients with
      thalamic haemorrhage. Based on the neuro-imaging findings we classified thalamic
      haematomas into four regional types and one global type according to the primary
      bleeding sites: (i) anterior type occurring in the territory of the
      tuberothalamic arteries, (ii) posteromedial type occurring in the territory of
      the thalamic-subthalamic paramedian arteries, (iii) posterolateral type occurring
      in the territory of the thalamogeniculate arteries. (iv) dorsal type occurring in
      the territory of the posterior choroidal arteries and (v) global type occupying
      the entire area of the thalamus. We studied the clinical and neuroimaging
      characteristics of each type. Eleven patients (7%) had the anterior type: these
      were the smallest haematomas and often ruptured into the anterior horn of the
      lateral ventricle. The major clinical signs were acute behavioural abnormalities:
      the clinical course was usually benign. Twenty-four patients (14%) had the
      posteromedial type in which haematomas often ruptured into the third ventricle,
      causing marked hydrocephalus, and often extended mediocaudally, involving the
      mesencephalon. The prognoses of this type depended on the presence of
      mesencephalic involvement which was associated with the worst outcome among the
      types even if the size of the haematoma itself was not large. The posterolateral
      type was most frequent (77 patients, 44%) and was characterized by large
      haematomas, rupture into the posterior horn of the lateral ventricle and frequent
      extension into the posterior limb of the internal capsule. Clinical signs
      included marked sensory and motor signs, hemineglect in right-side haematomas and
      language abnormalities with left-side haematomas. The case fatality with this
      type was relatively high (35%) and permanent neurologic sequelae frequently
      resulted. In the dorsal type (32 patients, 18%) haematomas were best visualized
      at the level of the body of the lateral ventricle on CT scans. The size was
      moderate and haematomas often extended posterolaterally into the adjacent
      subcortical white matter. Sensory and motor signs were common and about one third
      of the patients were first misdiagnosed as having lacunar infarcts. The prognoses
      were excellent. The global type (31 patients, 18%) of thalamic haemorrhage was
      clinically and radiologically very similar to the posterolateral type except that
      the haematomas were too large to define the bleeding focus. Severe sensory and
      motor signs were almost always present. In this type 25 patients died (the case
      fatality was 81%).

PMID- 9009995
TI  - Inclusion body myositis in HIV-1 and HTLV-1 infected patients.
AB  - Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy
      affecting patients over the age of 50 years. Dysimmune and degenerative
      aetiologies have been postulated, but viral infections have not been associated
      with the disease. Two HIV-I (human immunodeficiency virus type 1) infected men
      and one woman infected with HTLV-1 (human T cell leukaemia virus type 1)
      developed progressive proximal muscle weakness unrelated to antiretroviral
      therapy. Their muscle biopsies were studied by light and electron microscopy, by
      immunocytochemistry to determine the expression of major histocompatibility
      complex (MHC) molecules and identify the type of infiltrating cells and T cell
      receptor (TCR) subunits, and by reverse transcription-polymerase chain reaction
      (RT-PCR) and single or double immunocytochemistry to search for retrovirally
      infected endomysial cells. The clinical features were consistent with sporadic
      IBM. The muscle biopsies showed primary endomysial inflammation, red-rimmed
      vacuoles, amyloid deposits, eosinophilic inclusions, and small round fibres in
      groups, all diagnostic of IBM. The muscle fibres expressed MHC class-1 antigens
      and were invaded primarily by CD8+ T-lymphocytes preferentially bearing TCR V
      beta 5.1 and V beta 13 chains. The HIV-1 or HTLV-1 antigens were detected only on
      endomysial macrophages on or around muscle fibres, but not within the muscle
      fibres. We conclude that IBM occurs in HIV-1 and HTLV-1 infected individuals and
      has a clinical, histological and immunological pattern identical to sporadic IBM
      in the non-retrovirally infected patients. Retroviruses do not directly infect
      the muscle, but persistent retroviral infections may provide superantigenic
      stimulation and trigger an endomysial inflammatory response identical to that
      occurring in sporadic IBM.

PMID- 9009996
TI  - Clinical and molecular analysis of a large family with three distinct phenotypes
      of progressive muscular dystrophy.
AB  - We describe a unique six-generation, highly consanguineous family originating
      from an isolated mountainous village in the Russian province of Daghestan. Three
      separate clinical phenotypes of progressive muscular dystrophy were identified in
      this large family. Seven patients developed a classical limb-girdle variant of
      muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of
      ambulation within a 25-year course. The second group included three patients with
      a slowly progressive distal myopathy first manifested in the late teens and
      confined to the tibial and calf muscles. Each of these two phenotypes segregated
      independently as an autosomal recessive trait, and muscle biopsies showed non
      specific myopathic changes. Lastly, two male siblings exhibited an atypical
      variant of Duchenne muscular dystrophy confirmed by detection of a deletion in
      the dystrophin gene. To clarify the molecular basis of the polymorphic autosomal
      recessive form of muscular dystrophy in this kindred, we performed molecular
      genetic studies on 67 family members and obtained significant evidence for
      linkage to chromosome 2p. A maximum pairwise lod (logarithm of odds) score of
      5.64 was achieved at the zero recombination fraction (i.e. at theta = 0.00) for
      locus D2S291; multipoint linkage analysis confirmed the most likely location of a
      mutant gene near D2S291. The patients with LGMD and those with the distal
      muscular dystrophy phenotype share a common affected homozygous haplotype
      associated with the same founder chromosome; key recombinants defined D2S286 and
      D2S292 to be the closest loci flanking the mutant gene. Remarkably, two
      clinically distinct forms of autosomal recessive muscular dystrophy, LGMD type 2B
      (LGMD2B) and Miyoshi myopathy, were recently mapped to the same locus. We suggest
      that all three chromosome 2p-linked conditions may represent allelic disorders,
      i.e. different phenotypic expressions of a single gene.

PMID- 9009997
TI  - Central and peripheral respiratory electrophysiological studies in myotonic
      dystrophy.
AB  - Acute and chronic respiratory failure is a common and potentially life
      threatening feature in patients with myotonic dystrophy (MD). The causes may be
      varied, and can involve both the central and peripheral nervous system. To
      evaluate the incidence of respiratory muscle involvement and the function of the
      central motor inspiratory pathway to phrenic motor neurons we performed magnetic
      stimulation of the cortex and cervical spinal cord, phrenic nerve conduction
      studies and needle EMG of diaphragm and intercostal muscles in 25 patients with
      MD. The results were compared with those from 35 healthy subjects. In addition,
      pulmonary function tests, blood gas analyses and static mouth pressures were
      evaluated. Abnormalities in response to magnetic stimulation, including a reduced
      compound muscle action potential (CMAP) from the diaphragm and increased
      excitability threshold, indicated impaired central inspiratory drive in 20% of
      cases. Phrenic nerve conduction showed a reduced diaphragmatic CMAP amplitude in
      20%, and a delayed negative peak onset latency in 4% of cases. Abnormalities in
      diaphragm and intercostal muscle needle EMG were found in 76% of cases, these
      were mainly myotonic discharges (68%) and a decrease in the number of active
      motor units (36%). Patients with abnormal respiratory electrophysiological
      parameters had a significantly lower functional vital capacity (FVC; P = 0.005).
      The duration of the disease correlated negatively with diaphragmatic CMAP
      amplitude to phrenic nerve, but not magnetic, stimulation. Our results
      demonstrate that the involvement of the central inspiratory pathway is common in
      MD patients. Central and peripheral electrophysiological studies of the diaphragm
      should be considered in the diagnosis and management of patients with MD and
      dyspnoea.

PMID- 9009998
TI  - Abnormalities of ocular motility in myotonic dystrophy.
AB  - Are the oculomotor disturbances in myotonic dystrophy (MD), i.e. reduced smooth
      pursuit (SP) gain and reduced saccadic peak velocity (PV), of muscular or central
      origin? To answer this question the following two approaches were used. (i) The
      performance of SP was compared with the patient's ability to suppress the
      vestibulo-ocular reflex (VOR) visually (VOR suppression; VOR-S). In the latter
      task the SP system is involved, but the eyes hardly move within the orbits. A
      parallel impairment of SP and VOR-S would indicate a central dysfunction. (ii)
      Peak saccadic velocity was compared between two saccades performed to and fro in
      rapid succession. The intention was to measure any myotonic effect which might
      build up after the first saccade and slow down the second saccade. We studied 15
      MD patients and 15 age-matched controls. Stimuli for slow eye responses consisted
      of sinusoidal horizontal rotations of the SP target and/or the vestibular
      rotation chair at frequencies between 0.1 and 0.8 Hz. Saccades were analysed in
      terms of PV. accuracy, duration and latency, comparing centripetal versus
      centrifugal saccades at short and long intersaccadic intervals (ISI; 400 ms and
      900 ms, respectively). The SP gain was reduced in patients compared with the
      controls, the effect being most pronounced (32% less) at the highest stimulus
      frequency. Whereas VOR was normal in the patients, VOR-S was clearly impaired
      (50% worse at 0.8 Hz). Despite normal saccadic accuracy, peak saccadic velocity
      was significantly lower in the patient group (23% less for saccades of 12 degrees
      amplitude), similarly for centrifugal and centripetal saccades; all these
      differences were independent of the ISI. Latency was normal with centrifugal
      saccades, but was considerably increased with centripetal saccades at short ISI
      (67% longer compared with controls). The observation of a parallel degradation of
      SP and VOR-S in the patients is interpreted in terms of a central deficit in the
      SP pathways. Thus, it appears that slow eye movements were not impaired by muscle
      dystrophy and myotonia to a considerable degree in our patients. The increase in
      saccadic latency for centripetal saccades at the short ISI also reflects a
      central deficit. However, the observed slowing of saccades might have a myopathic
      or neural origin; a distinction was not possible at present. A myotonic origin of
      the saccade slowing seems unlikely, because the effect was independent of the
      presaccadic activation of the relaxing (antagonistic) eye muscle.

PMID- 9009999
TI  - Disorders of binocular control of eye movements in patients with cerebellar
      dysfunction.
AB  - Recent research has implicated the cerebellum in conjugate ocular motor control,
      including steady gaze-holding and accuracy of pursuit and saccades. Whether the
      cerebellum also has a role in the control of the alignment of the eyes during
      fixation and of the yoking of the eyes during movement i. less certain. We have
      studied binocular (disconjugate) ocular motor control in nine patients with
      cerebellar dysfunction and compared the results with those of normal subjects.
      Eye alignment during fixation and the yoking of the eyes during and immediately
      after saccades were quantified by recording the movements of both eyes using
      scleral search coils. Patients had disturbances of ocular alignment. All had an
      esophoria during monocular viewing and many an esotropia during binocular
      viewing, implying an increase in convergence tone. Most had a vertical
      misalignment that varied with horizontal eye position ('alternating skew
      deviation'). Patients showed conjugate dysmetria (saccade under- or overshoot and
      postsaccade drift) and disconjugate dysmetria (the eyes were poorly yoked during
      and immediately after saccades). Both the conjugate and disconjugate
      abnormalities were incommitant, i.e. they varied with orbital eye position.
      Correlations amongst the various abnormalities suggested that one part of the
      cerebellum, perhaps the dorsal vermis and the underlying posterior fastigial
      nucleus, controls the conjugate size of saccades and that another part of the
      cerebellum, perhaps the flocculus/paraflocculus, controls the yoking of the eyes
      during saccades and both the disconjugate and conjugate components of postsaccade
      drift.

PMID- 9010000
TI  - Deficits of smooth pursuit eye movements after frontal and parietal lesions.
AB  - To assess the contribution of the human frontal and parietal cortices to smooth
      pursuit (SP) eye movements, we recorded ocular motor responses to predictable
      (periodic) and unpredictable (step-ramp) foveal pursuit stimuli and to constant
      velocity optokinetic full-field motion in 31 patients with chronic focal
      unilateral hemispheric lesions and in 50 age-related healthy adults, using
      infrared reflection oculography. Lesions were located either in the posterior
      parietal cortex (PPC), leaving the visual fields largely intact, or in the region
      of the frontal eye fields (FEF), the dorsolateral prefrontal cortex (PFC) or the
      supplementary motor area (SMA). We found (i) directional deficits in terms of
      lower pursuit velocities with ipsiversive target motion, more pronounced with
      predictable than with step-ramp stimuli, in patients with FEF lesions more
      frequently (in each of the four cases) than in patients with PPC lesions (in four
      out of 13 cases with foveal and in eight out of 13 cases with optokinetic
      stimulation); (ii) a relatively prolonged latency of direction reversal with
      periodic constant-velocity stimuli after SMA lesions (three cases), implying
      impaired anticipation of the target trajectory; (iii) no SP deficits following
      selective prefrontal lesions (eight cases); (iv) in some patients with PPC
      lesions (four out of 13) retinotopic deficits of SP initiation in both horizontal
      directions when step-ramp stimuli started in the contralesional hemifield,
      including prolonged pursuit latencies, which were independent of contralateral
      visual hemineglect. Directional and retinotopic SP deficits in patients with PPC
      lesions corresponded to SP deficits after unilateral lesions of middle temporal
      (MT) and medial superior temporal (MST) cortex in the monkey, and occurred only
      when lesions included the junction of Brodmann areas 19, 37 and 39, where the
      human homologues of MT and MST are assumed to lie. In conclusion, human SP eye
      movements are controlled, as in non-human primates, by a network of frontal and
      posterior cortical areas. Selective damage to each of these areas impairs
      specific SP subfunctions, reflecting subsequent stages of cortical processing
      from visual motion input to SP-related motor output.

PMID- 9010001
TI  - Motion specific responses from a blind hemifield.
AB  - In a previous study we showed that fast moving stimuli activate V5, an area
      specialized for motion, at very short latencies through a pathway that reaches it
      without passing through V1. Using the same technique of visual evoked responses,
      we have tested our conclusions by studying patient GY, whose V1 is damaged but
      whose V5 is intact. In spite of the contralateral hemi-blindness due to his V1
      lesion, GY has a residual visual capacity that allows him to perceive,
      consciously, fast but not slow moving stimuli presented in his affected
      hemifield. By stimulating GY's 'blind' hemifield and comparing the responses with
      those obtained from normal subjects, we were able to study the relative
      contribution of V1 and V5 to the visual evoked response to motion in normal
      subjects. We found that GY's early response to fast motion is preserved and
      correlates with activity elicited in control subjects over area V5, while slow
      motion, pattern offset, and pattern reversal stimuli failed to elicit responses
      in GY. The results confirm our previous conclusions: namely, that the early part
      of the motion evoked response is generated in area V5 and that signals reach this
      area through a dynamically parallel pathway that bypasses area V1. They go on to
      demonstrate that neurophysiological activity in the prestriate cortex correlates
      with the conscious visual perception of motion.

PMID- 9010002
TI  - Age and hemisphere effects on dendritic structure.
AB  - The dendritic structures of 187 small supragranular pyramidal neurons of the
      posterior superior temporal gyrus were studied with rapid Golgi impregnations in
      postmortem samples from 10 men aged 21-71 years. The number of primary basilar
      dendritic branches, the total number of basilar dendritic endings, the total
      basilar dendritic length, the total number of visible basilar dendritic spines
      and the cell soma sizes were all positively inter-correlated and all features
      were correlated to age (r = -0.77, -0.88, -0.82, -0.72, -0.86, respectively; all
      P < 0.05). These neuronal measures all correlated with brain weight (r = 0.79*,
      0.65*, 0.51, 0.45, 0.55, respectively; *denotes P < 0.05). A first principle
      component derived from the inter-correlations of the neuronal features plus brain
      weight correlated almost perfectly with age (r = -0.93). The neuronal features
      differed between the right and left hemispheres (Wilks' Lambda = 0.91, P < 0.01).
      Post hoc tests showed that the dendritic trees of the right hemisphere were
      longer (P = 0.002), more branched (P = 0.008) and possessed more dendritic spines
      (P = 0.0009; Sheffe's tests). In conclusion, there are hemispheric differences in
      the dendritic structure of the small pyramidal neurons of presumptive human
      speech cortex and its right hemisphere analogue. Generalized neuronal atrophy is
      highly correlated with both brain weight and age, and is a candidate process to
      explain the decline in cognition with age.

PMID- 9010003
TI  - Startle reflex and emotion modulation impairment after a right amygdala lesion.
AB  - In the present study, startle responses during resting states as well as during
      the presentation of a set of emotive slides were recorded from a 32-year-old male
      patient with a rare localized lesion of the right amygdala. The startle reflex is
      a response modulated by affective states: it has been reliably used in the
      literature to measure the aversiveness of emotive stimuli. The animal literature
      has shown that the circuit of this reflex is directly influenced by amygdala
      projections. The startle responses of the patient were compared with those of
      eight age-matched normal subjects. The patient's startle amplitudes showed an
      overall impaired response and an inhibited reflex contralateral to the lesion. In
      addition, he failed to show the typical startle potentiation induced by an
      aversive emotive background. The data confirm, in the human, previous results
      from the literature in other species on amygdala involvement in startle and
      emotional responses. Furthermore, the observation of the importance of the right
      amygdala in the modulation of emotion is consistent with the hypothesis of right
      hemisphere specialization for aversive emotions. The results are discussed in the
      context of the literature on human amygdala lesions.

PMID- 9010004
TI  - Presymptomatic hippocampal atrophy in Alzheimer's disease. A longitudinal MRI
      study.
AB  - The hippocampal formation (HF) is known from pathological and MRI studies to be
      severely atrophied in established Alzheimer's disease. However, it is unclear
      when the earliest changes in the HF occur. We performed a longitudinal study of
      asymptomatic individuals at risk of autosomal dominant familial Alzheimer's
      disease in order to assess presymptomatic changes in the HF. Seven at risk
      members of a familial Alzheimer's disease pedigree associated with the amyloid
      precursor protein 717 valine to glycine mutation underwent serial MR scanning and
      neuropsychological assessments over 3 years. These assessments were compared with
      results from 38 normal controls. During the study three at risk subjects became
      clinically affected. Volumetric measurement of the HF showed that asymmetrical
      atrophy developed in these subjects before the appearance of symptoms. Verbal and
      visual memory measures declined in parallel with hippocampal loss. A loss of up
      to 8% per annum of the volume of the HF occurred in the 2 years over which
      symptoms first appeared. These findings may have implications for early diagnosis
      of Alzheimer's disease.

PMID- 9010005
TI  - Progressive cerebral atrophy in multiple sclerosis. A serial MRI study.
AB  - Recent studies of the spinal cord and cerebellum have highlighted the importance
      of atrophy in the development of neurological impairment in multiple sclerosis.
      We have therefore developed a technique to quantify the volume of another area
      commonly involved pathologically in multiple sclerosis: the cerebral white
      matter. The technique we describe extracts the brain from the skull on four
      contiguous 5 mm periventricular slices using an algorithm integrated in an image
      analysis package, and quantifies their volume. Intra-observer scan-rescan
      reproducibility was 0.56%. We have applied this technique serially to 29 patients
      with multiple sclerosis selected for an 18-month treatment trial with a
      monoclonal antibody against CD4+ lymphocytes (deemed clinically ineffective). A
      decrease in volume beyond the 95% confidence limits for measurement variation was
      seen in 16 patients by the end of the 18-month period. The rate of development of
      atrophy was significantly higher in those who had a sustained deterioration in
      their Kurtzke expanded disability status scale (EDSS) score compared with those
      who did not (respective means: -6.4 ml year-1 and -1.8 ml year-1, P < 0.05) but
      in both groups these changes differed significantly from baseline (P < 0.05).
      Baseline T2 lesion load, change in T2 lesion load over 18 months and the volume
      of new gadolinium enhancing lesions on monthly scans for the first 10 months
      showed no correlation with the development of atrophy. This study demonstrates
      that progressive cerebral atrophy can be detected in individual patients with
      multiple sclerosis, correlates with worsening disability and gives additional
      information to that obtained with conventional MRI. The effect of putative
      therapies aimed at preventing disability could be objectively assessed by this
      measure.

PMID- 9010006
TI  - Tumour necrosis factor-alpha increases intracellular Ca2+ and induces a
      depolarization in cultured astroglial cells.
AB  - Tumour necrosis factor (TNF)-alpha, a strong immune mediator, is released within
      the brain during inflammatory diseases and contributes to immunological
      activation of glial cells. Here we report that, in astrocytes, TNF-alpha also
      affects the intracellular Ca2+ homeostasis and basic electrophysiological
      properties such as the membrane potential. Using the Ca2+ indicator dye fura-2 in
      a cell culture model, we found that TNF-alpha (10-1000 U ml-1), but not
      interleukin 1 or 6, induced a slow but more than two-fold increase of the
      intracellular Ca2+ concentration, which could be blocked by Co2+ (1.0 mM),
      verapamil (100 microM) or omission of external Ca2+. This intracellular Ca2+
      increase was accompanied by a marked decrease of the membrane potential by 35 mV.
      CSF of patients with bacterial meningitis, known to contain large amounts of TNF
      alpha, induced a similar depolarization of astrocytes, which was markedly reduced
      by a neutralizing anti-TNF-alpha antibody. We conclude that TNF-alpha induces an
      increase of intracellular Ca2+ and a depolarization in astrocytes with the
      consequence of disturbing voltage-dependent glial functions such as regulation of
      local ion concentrations and glutamate uptake. During inflammatory CNS diseases
      this immuno-electrical coupling may contribute to an impairment of neuronal
      function.

PMID- 9010007
TI  - Changes in excitability and impulse transmission following prolonged repetitive
      activity in normal subjects and patients with a focal nerve lesion.
AB  - The present study was undertaken to document the excitability changes produced by
      prolonged high-frequency trains of impulses and to determine whether these
      changes in excitability would impair neural transmission in cutaneous afferents
      of patients with focal slowing of conduction across the carpal tunnel. A
      submaximal test stimulus was used to measure the changes in axonal excitability
      following trains of supramaximal stimuli delivered at 200 Hz for 30 s, 1 min or 2
      min. These trains produced a prolonged depression in excitability in normal axons
      with gradual recovery to control levels over 20-30 min, presumably due to
      hyperpolarization associated with activation of the electrogenic Na+/K+ pump. The
      decrease in excitability was demonstrable at nerve segments remote from the site
      of tetanic stimulation. Based on these findings, the effects on neural
      transmission were then assessed in normal subjects and patients using a
      supramaximal test stimulus following a 1-min tetanic train. In normal subjects
      there was a small activity-dependent decrease in amplitude of the compound
      sensory action potential (CSAP) associated with a prolongation in its latency. In
      patients with focal slowing of conduction across the carpal tunnel there was a
      more marked post-tetanic prolongation in latency, but the reduction in amplitude
      of the maximal CSAP was no greater than in the control subjects. It is concluded
      that activity-dependent conduction block is not a major cause of symptoms in
      carpal tunnel syndrome. It is suggested that the conduction slowing seen in
      patients with mild-moderate carpal tunnel syndrome could result from mechanisms
      other than demyelination.

PMID- 9010008
TI  - A prospective study of suramin-induced peripheral neuropathy.
AB  - Suramin is an investigational drug that has shown therapeutic activity in hormone
      refractory metastatic prostate cancer in Phase I/II trials. Dose-limiting
      neurotoxicity remains the most serious complication of suramin treatment. We
      performed a prospective study to define the incidence, severity, characteristics,
      and dose relationships of suramin-induced peripheral neuropathy. Twenty-two
      patients who received suramin in a Phase-I trial underwent baseline and serial
      follow-up neurological evaluations consisting of history, examination, nerve
      conduction studies and quantitative sensory testing (QST). Suramin was
      administered intravenously in escalating dosages by using a 5-day schedule
      (repeated monthly), with the dose, determined by a population pharmacokinetic
      model, to accomplish 30-min post-infusion concentrations of 300 micrograms ml-1
      (cohort I), 350 micrograms m-1 (cohort II) and 400 micrograms ml-1 (cohort III).
      Twelve patients developed a mild, axonal, length-dependent, sensory-motor poly
      neuropathy. Three other patients developed a subacutely progressive, functionally
      disabling, demyelinating neuropathy; sural nerve biopsy in two patients showed
      lymphocytic inflammation. These three patients improved after drug
      discontinuation and plasmapheresis. Although there was no apparent correlation
      between the cumulative dose and the severity of the neuropathy, no patient from
      cohort I, but 88% of patients from cohorts II and III, developed neuropathy. We
      conclude that when suramin is used at peak concentrations of > or = 350
      micrograms ml-1 its administration is associated with two patterns of neuropathy,
      a distal axonal neuropathy and an inflammatory demyelinating neuropathy that is
      partially reversible. Neurological monitoring for development of neuropathy will
      improve the safety of suramin use in future clinical studies.

PMID- 9010009
TI  - The prognosis and main prognostic indicators of Guillain-Barre syndrome. A
      multicentre prospective study of 297 patients. The Italian Guillain-Barre Study
      Group.
AB  - To assess the prognosis of the Guillain-Barre syndrome and identify the main
      prognostic indicators, 297 patients with Guillain-Barre syndrome recruited
      through a network of Italian centres were followed up for 24 months or until
      clinical recovery, whichever was earliest. For each patient the time to plateau,
      improvement, clinical recovery, or death was calculated, and prognostic
      indicators (age, sex, antecedent events, disability at admission and nadir,
      electrophysiological patterns) and treatments were noted. The mean duration of
      follow-up was 309 days. During this period, 212 patients (71%) recovered, 48
      (16%) had residua and 33 (11%) died. The mean times to nadir, improvement and
      clinical recovery were 12, 28 and 200 days. Using life-tables and survival
      curves, the cumulative probability of achieving the plateau of symptoms was 73%
      by 1 week and 98% by 4 weeks. Improvement started during the first week in 36% of
      cases and within 4 weeks in 85%. The rates of clinical recovery at 1 and 4 weeks,
      6, 12 and 24 months were 4, 24, 57, 70 and 82%, respectively. The chance of
      recovery was significantly affected by age, antecedent gastroenteritis,
      disability, electrophysiological signs of axonopathy, latency to nadir and
      duration of active disease. The main treatments did not seem to affect the chance
      of recovery.

PMID- 9010010
TI  - Collateral sprouting of cutaneous nerves in man.
AB  - Cutaneous nerve collateral sprouting was studied in 20 adults in whom a forearm
      cutaneous nerve had been resected from the upper arm, such that any recovery of
      cutaneous nerve function could not be accounted for by nerve regeneration. Ten
      patients entered the study immediately following surgery and the remainder at
      intervals thereafter, permitting a longitudinal study covering a 27-month period.
      Modality-specific stimuli were used to study light touch, sharp pain, cooling,
      warming and heat pain sensation. Efferent sympathetic C fibre function was
      determined by measuring sweating in response to total body heating. Though the
      patients described considerable subjective reduction in the sensory defect within
      2 months, by 10-15 months the objective sensory tests showed encroachment at the
      margin by only 6 mm (P < 0.05) for light touch, 7 mm (P < 0.01) for sharp pain
      and 11.5 mm (P < 0.001) for heat pain, with no significant change for warming or
      cooling. By 24 months, recovery of sweating was evident within the zone of
      persistent sensory loss, for > or = 3 cm beyond the initial light touch margin (P
      < 0.005). This finding has important clinical implications as it calls into
      question the reliance placed on the recovery of sweating as evidence of nerve
      regeneration.

PMID- 9010011
TI  - Differential activation of the prefrontal cortex in successful and unsuccessful
      memory retrieval.
AB  - Six subjects underwent PET scans while they performed three versions of a
      recognition memory test for words and three versions of a control task. In each
      memory condition, the subjects discriminated between words presented in a prescan
      study list and words new to the experiment. During the 30 s scanning interval,
      the ratio of old and new words was 0:20, 4:16 or 16:4, depending on the
      experimental condition. Outside this interval, the ratio was 50:50 in all three
      conditions. The requirement in the control task was to discriminate between two
      character strings, the ratios of which were also manipulated during the 30 s
      scanning interval. Employing the control task as a covariate, analysis with
      statistical parametric mapping revealed that regional cerebral blood flow (rCBF)
      covaried with increasing density of old items in three regions of prefrontal
      cortex: right dorsolateral [Brodmann area (BA) 9/46], right medial (BA 32/8) and
      bilateral frontopolar cortex (BA 10). It is concluded that the prefrontal cortex,
      especially in the right hemisphere, is more active when a retrieval attempt
      succeeds than when it fails. This finding is consistent with the idea that the
      prefrontal cortex supports processes that operate selectively on the products of
      memory retrieval.

PMID- 9010013
TI  - Regional changes in [18F]dopa metabolism in the striatum in Parkinson's disease.
AB  - We have investigated regional changes in dopamine metabolism within the basal
      ganglia with clinical progression of idiopathic Parkinson's disease, using
      coregistration of [18F]dopa-PET and MRI images and comparing six normal subjects
      with 15 Parkinson's disease patients in a cross-sectional study. We have
      demonstrated that [18F]dopa metabolism in the dorsal putamen is reduced to almost
      50% of normal both caudally and rostrally early in the disease whilst the ventral
      putamen is not significantly affected. With progression of symptoms there is loss
      of dopa metabolism from the ventral putamen, the ventrocaudal putamen in advance
      of the ventrorostral putamen. Throughout the disease the ventrorostral putamen is
      relatively preserved; even in the most advanced group [18F]dopa uptake is reduced
      here by only 30%. We conclude that the progression of Parkinson's disease is
      associated with a focal process affecting only the dorsal putamen in its early
      (and preclinical) phase then affecting the ventral putamen with increasing
      disease severity.

PMID- 9010012
TI  - Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene
      carriers and patients with Huntington's disease.
AB  - We used PET scans with the tracers [18F]fluorodeoxyglucose (FDG) and
      [11C]raclopride (RACLO) to study glucose metabolism and dopamine D2 receptor
      binding in the caudate nucleus and putamen of 18 carriers of the Huntington's
      disease gene mutation (10 asymptomatic subjects and eight untreated symptomatic
      Huntington's disease patients in an early disease stage). We also performed MRI
      scans and measured the bicaudate ratio (BCR) in the same subjects. Data were
      compared with those from nine mutation-negative members of Huntington's disease
      families and separate groups of age matched controls. The PET scans were repeated
      1.5-3 years later in six of the asymptomatic gene carriers. Symptomatic
      Huntington's disease patients showed a marked reduction of FDG and RACLO uptake
      in the caudate nucleus and putamen and a significant increase of BCR.
      Asymptomatic mutation carriers revealed significant hypometabolism in the caudate
      nucleus and putamen. The RACLO binding was significantly decreased in the
      putamen. Decrements of caudate nucleus tracer uptake, particularly RACLO,
      correlated significantly with BCR increases in both symptomatic and asymptomatic
      gene carriers. In asymptomatic carriers, metabolic and receptor binding decreases
      were also significantly associated with the CAG repeat number but not with the
      individual's age. Discriminant function analysis correctly classified clinical
      and genetic status in 24 of 27 subjects on the basis of their striatal PET values
      (83% sensitivity and 100% specificity). Three asymptomatic mutation carriers were
      classified/grouped together with mutation-negative subjects, indicating that
      these individuals had normal striatal RACLO and FDG uptake. Follow-up PET data
      from gene-positive subjects showed a significant reduction in the mean striatal
      RACLO binding of 6.3% per year. Striatal glucose metabolism revealed an overall
      non significant 2.3% decrease per year. These data indicate that asymptomatic
      Huntington's disease mutation carriers may show normal neuronal function for a
      long period of life. These findings also suggest that it may be possible to
      predict when an asymptomatic gene carrier will develop clinical symptoms from
      serial PET measurements of striatal function.

PMID- 9010014
TI  - Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.
AB  - PET measurements of regional cerebral blood flow (rCBF) were used to explore
      frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). An activation
      paradigm of executive frontal lobe function (verbal fluency), which contrasted
      rCBF during word generation and word repetition, was used. Two groups of ALS
      patients, defined by the presence or absence of cognitive impairment (ALSi)
      (impaired, n = 6: ALSu unimpaired, n = 6) were compared with healthy age-matched
      controls (n = 6). Patient selection was based on prior performance on a written
      test of verbal fluency. Additional neuropsychological assessment of the patients
      revealed evidence of executive and memory dysfunction in the ALSi group only,
      with marked deficits in tests of intrinsic generation. The ALSi patients
      displayed significantly (P < 0.001) impaired activation in cortical and
      subcortical regions including the dorsolateral prefrontal cortex (DLPFC; areas 46
      and 9), lateral premotor cortex (areas 8 and 6), medial prefrontal and premotor
      cortices (areas 8 and 9), insular cortex bilaterally and the anterior thalamic
      nuclear complex. Although the three groups showed matched word generation
      performance on the scanning paradigm, the ALSu group displayed a relatively
      unimpaired pattern of activation. These results support the presence of extra
      motor neuronal involvement, particularly along a thalamo-frontal association
      pathway, in some non-demented ALS patients. In addition, this study suggests
      dysfunction of DLPFC in some ALS patients with associated cognitive impairments.

PMID- 9010015
TI  - Acute effects of levodopa on neuropsychological performance in stable and
      fluctuating Parkinson's disease patients at different levodopa plasma levels.
AB  - The contribution of dopaminergic systems to cognitive defects in Parkinson's
      disease and the cognitive effects of levodopa remain controversial. The levodopa
      plasma levels and the neuropsychological performance of 10 parkinsonian patients
      with a stable motor response to the drug and 10 matched parkinsonian patients
      with a 'wearing-off' phenomenon were studied 12 h after levodopa was withdrawn
      (time zero), and at 1 h and 4 h after an oral dose of levodopa (i.e. at '+1H' and
      '+4H'), to investigate whether discrete cognitive domains are more sensitive to
      levodopa in parkinsonian patients with the wearing-off phenomenon. Considering
      the 20 patients as a whole, levodopa significantly diminished the response time
      in verbal and visuospatial memory tests, the extradimensional matching test and
      the Wisconsin card sorting test (WCST), without significantly improving or
      worsening the patient's accuracy. A significant group-by-time effect was only
      evident in the WCST; while in stable patients levodopa produced no changes,
      wearing-off patients significantly reduced the number of categories achieved and
      had more perseverative errors at +1H, recovering at +4H. These results confirm
      previous findings of selective adverse effects of levodopa on highly demanding
      executive tasks in Parkinson's disease and additionally suggest that some
      previous discrepancies between studies may be accounted for by lack of
      differentiation between stable and wearing-off conditions. 'Frontal' disturbances
      on neuropsychological tests with levodopa may become evident only after massive
      degeneration of the dopamine systems has occurred.

PMID- 9010016
TI  - Temporal lobe epilepsy caused by mesial temporal sclerosis and temporal
      neocortical lesions. A clinical and electroencephalographic study of 46
      pathologically proven cases.
AB  - This study aims to determine whether there are important clinico-electrical
      differences between patients with temporal lobe epilepsy (TLE) secondary to
      mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete
      temporal neocortical lesion (NL). The case histories, interictal EEG, seizure
      semiology, ictal EEG and postoperative outcome of 46 pathologically proven
      patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC)
      was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a
      significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There
      were no statistically significant differences in the incidence or nature of
      auras. No statistically significant differences between the groups were found in
      the interictal-EEG. With ictal semiology dystonic posturing occurred more
      frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/
      twitching occurred earlier in the seizures of NL patients (median 19 s versus 35
      s, P < 0.05). There was an increased frequency of fast rhythmic sharp waves (> 4
      Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The
      patients with NL developed bilateral ictal EEG changes more often (mean 55%
      versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The
      onset of ictal EEG seizure activity was bilateral more often in patients with NL
      (20% versus 4%, P < 0.005). There were no significant differences between the two
      groups for any of the video-EEG features, in terms of whether or not the feature
      occurred at least once in an individual patients. There was a tendency for MTS
      patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P =
      0.057). However, all the NL patients who were not free of seizures had had an
      incomplete lesion resection. We conclude that there are a number of clinico
      electrical differences between patients with mesial TLE (MTLE) and patients with
      neocortical TLE (NCTLE), but that none of these are sufficient to allow a
      distinction to be made in an individual patient.

PMID- 9010017
TI  - Inflammatory brain changes in Lyme borreliosis. A report on three patients and
      review of literature.
AB  - Despite a rapid increase in the number of patients with Lyme neuroborreliosis
      (LNB), its neuropathological aspects are poorly understood. The objective of this
      study was evaluation of neuropathological, microbiological, and magnetic
      resonance imaging (MRI) findings in three patients with the Borrelia burgdorferi
      infection and neurological disease from whom brain tissue specimens were
      available. Perivascular or vasculitic lymphocytic inflammation was detected in
      all specimens. Large areas of demyelination in periventricular white matter were
      detected histologically and by MRI in one patient. The disease had a fatal
      outcome in this patient. Brain MRI suggested malignancies in two patients before
      histopathological studies were carried out. One of these two patients was a child
      with sudden hemiparesis. Another was a 40-year-old man presenting with epileptic
      seizures and MRI-detected multifocal lesions, which disappeared after repeated
      courses of antibiotics. We conclude that cerebral lymphocytic vasculitis and
      multifocal encephalitis may be associated with B. burgdorferi infection. The
      presence of B. burgdorferi DNA in tissue samples from areas with inflammatory
      changes indicates that direct invasion of B. burgdorferi may be the pathogenetic
      mechanism for focal encephalitis in LNB.

PMID- 9010018
TI  - Channels of the corpus callosum: evidence from simple reaction times to
      lateralized flashes in the normal and the split brain.

PMID- 9010019
TI  - Modelling the consequences of interactions between tumour cells.
AB  - Classical models of tumorigenesis assume that the mutations which cause tumours
      to grow act in a cell-autonomous fashion. This is not necessarily true. Sometimes
      tumour cells may adopt genetic strategies that boost their own replication and
      which also influence other cells in the tumour, whether directly or as a side
      effect. Tumour growth as a whole might be enhanced or retarded. We have used
      mathematical models to study two non-autonomous strategies that tumour cells may
      use. First, we have considered the production by tumour cells of an angiogenesis
      growth factor that benefits both the cell from which it originates and
      neighbouring cells. Second, we have analysed a situation in which tumour cells
      produce autocrine-only or paracrine-only growth factors to prevent programmed
      cell death. In the angiogenesis model, stable genetic polymorphisms are likely to
      occur between cells producing and not producing the growth factor. In the
      programmed cell death model, cells with autocrine growth factor production can
      spread throughout the tumour. Production of paracrine-only growth factor is never
      selected because it is 'altruistic' (that is of no benefit to the cell that makes
      the growth factor), despite being potentially beneficial to tumour growth as a
      whole. No polymorphisms can occur in the programmed cell death model. Production
      of angiogenesis and other growth factors in tumours may be under stable genetic,
      rather than epigenetic, control, with implications for therapies aimed at such
      targets. Many of the mutations observed in tumours may have non-autonomous
      effects.

PMID- 9010020
TI  - Effect of glucose transport inhibitors on vincristine efflux in multidrug
      resistant murine erythroleukaemia cells overexpressing the multidrug resistance
      associated protein (MRP) and two glucose transport proteins, GLUT1 and GLUT3.
AB  - The relationship between mammalian facilitative glucose transport proteins (GLUT)
      and multidrug resistance was examined in two vincristine (VCR)-selected murine
      erythroleukaemia (MEL) PC4 cell lines. GLUT proteins, GLUT1 and GLUT3, were
      constitutively coexpressed in the parental cell line and also in the VCR-selected
      cell lines. Increased expression of the GLUT1 isoform was noted both in the PC
      V40 (a non-P-glycoprotein, mrp-overexpressing subline) and in the more resistant
      PC-V160 (overexpressing mrp and mdr3) cell lines. Overexpression of GLUT3 was
      detected only in the PC-V160 subline. An increased rate of facilitative glucose
      transport (Vmax) and level of plasma membrane GLUT protein expression paralleled
      increased VCR resistance, active VCR efflux and decreased VCR steady-state
      accumulation in these cell lines. Glucose transport inhibitors (GTIs),
      cytochalasin B (CB) and phloretin blocked the active efflux and decreased steady
      state accumulation of VCR in the PC-V40 subline. GTIs did not significantly
      affect VCR accumulation in the parental or PC-V160 cells. A comparison of protein
      sequences among GLUT1, GLUT3 and MRP revealed a putative cytochalasin B binding
      site in MRP, which displayed 44% sequence similarity/12% identity with that
      previously identified in GLUT1 and GLUT3; these regions also exhibited a similar
      hydropathy plot pattern. The findings suggested that CB bound to MRP and directly
      or indirectly lowered VCR efflux and/or CB bound to one or both GLUT proteins,
      which acted to lower the VCR efflux mediated by MRP. This is the first report of
      a non-neuronal murine cell line that expressed GLUT3.

PMID- 9010021
TI  - Plasma clearance, biodistribution and therapeutic properties of mitoxantrone
      encapsulated in conventional and sterically stabilized liposomes after
      intravenous administration in BDF1 mice.
AB  - Mitoxantrone can be efficiently loaded into large unilamellar vesicles using a
      transmembrane pH gradient. Release studies indicate that these drug-loaded
      carriers are highly stable and even after dissipation of the residual pH gradient
      retain more than 85% of encapsulated mitoxantrone following dialysis at 37
      degrees C for 5 days. In murine studies we have compared the plasma clearance and
      biodistribution of both mitoxantrone and liposomal lipid following intravenous
      administration of free drug or mitoxantrone encapsulated in either conventional
      or sterically stabilized liposomes. In contrast to the rapid blood clearance
      observed for free mitoxantrone, both liposomal systems provided extended
      circulation lifetimes, with over 90% of the drug present 1 h after administration
      and 15-30% remaining at 24 h. In agreement with previous reports, longer plasma
      half-lives were observed for sterically stabilized liposomes than for
      conventional systems. In addition, a strong correlation between drug and carrier
      biodistribution was seen, with uptake occurring mainly in the liver and spleen
      and paralleling plasma clearance. This would suggest that tissue disposition
      reflects that of drug-loaded liposomes rather than the individual components.
      Liposomal encapsulation also significantly reduced mitoxantrone toxicity,
      allowing administration of higher, more efficacious drug doses. In a murine L1210
      tumour model, for example, no long-term survivors were seen in animal groups
      treated with free drug, whereas at the maximum therapeutic dose of liposomal
      mitoxantrone survival rates of 40% were observed.

PMID- 9010022
TI  - Mutations at codon 974 of the DPYD gene are a rare event.
AB  - A mutation at codon 974 of the dihydropyrimidine dehydrogenase (DPD) gene was
      previously described in a cancer patient with undetectable DPD enzyme activity
      who experienced severe toxicity when treated with 5-fluorouracil. We have studied
      the frequency of this mutation in 29 Scottish subjects with low DPD enzyme
      activity and in 274 American subjects. We detected no mutations in the 606
      alleles studied and conclude that mutations at codon 974 are a rare event.

PMID- 9010023
TI  - Proton relaxation times and interstitial fluid pressure in human melanoma
      xenografts.
AB  - The interstitial fluid pressure (IFP) and the proton spin-lattice and spin-spin
      relaxation times (T1 and T2) of some experimental tumours have been shown to be
      related to tumour water content. These observations have led to the hypothesis
      that magnetic resonance imaging (MRI) might be a clinically useful non-invasive
      method for assessment of tumour IFP. The purpose of the work reported here was to
      examine the general validity of this hypothesis. R-18 human melanoma xenografts
      grown intradermally in Balb/c nu/nu mice were used as the tumour model system.
      Median T1 and T2 were determined by spin-echo MRI using a 1.5-T clinical whole
      body tomograph. IFP was measured using the wick-in-needle technique. No
      correlation was found between tumour IFP and fractional tumour water content.
      Moreover, there was no correlation between median T1 or T2 and IFP, suggesting
      that proton T1 and T2 values determined by MRI cannot be used clinically to
      assess tumour IFP and thereby to predict the uptake of macromolecular therapeutic
      agents.

PMID- 9010024
TI  - Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell
      lung cancer.
AB  - As chromosomes 2p and 3p are frequent targets for genomic instability in lung
      cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur
      in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by
      polymerase chain reaction (PCR) assay replication errors (RER) and loss of
      heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64
      paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA
      NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR
      single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic
      sequencing, as well as their relationship with clinical outcome. Forty-two of the
      64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected
      in 23 tumours (36%). Among patients with stage I disease, the 5-year survival
      rate was 80% in those whose tumours had no evidence of RER and 26% in those with
      RER (P = 0.005). No correlation was established between RER phenotype and LOH, K
      ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for
      death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for
      all other evaluated factors, including p53, K-ras, LOH, histological type, tumour
      differentiation and TNM stage, suggesting that microsatellite instability on
      chromosomes 2p and 3p may play a role in NSCLC progression through a different
      pathway from the traditional tumour mechanisms of oncogene activation and/or
      tumour-suppressor gene inactivation.

PMID- 9010025
TI  - Genetic changes associated with the acquisition of androgen-independent growth,
      tumorigenicity and metastatic potential in a prostate cancer model.
AB  - Genetic changes underlying the progression of human prostate cancer are
      incompletely understood. Recently, an experimental model system that resembles
      human prostate cancer progression was developed based on the serial passage of an
      androgen-responsive, non-tumorigenic LNCaP prostate cancer cell line into athymic
      castrated mice. Six different sublines, derived after one, two or three rounds of
      in vivo passage, sequentially acquired androgen independence and tumorigenicity
      as well as metastatic capacity. Here, we used comparative genomic hybridization
      (CGH) and locus-specific fluorescence in situ hybridization (FISH) analysis to
      search for genetic changes that may underlie the phenotypic progression events in
      this model system. Six genetic aberrations were seen by CGH in the parental LNCaP
      cell line. The derivative sublines shared virtually all these changes, indicating
      a common clonal origin, but also contained 3-7 additional genetic changes. Gain
      of the 13q12-q13 chromosomal region as well as losses of 4, 6q24-qter, 20p and
      21q were associated with androgen independence and tumorigenicity with additional
      changes correlating with metastasis. In conclusion, an accumulation of genetic
      changes correlates with tumour progression in this experimental in vivo model of
      prostate cancer progression. It is possible that the specific chromosomal
      aberrations involved in this model system may provide clues to the location of
      genes involved in human prostate cancer progression and metastasis.

PMID- 9010026
TI  - Plateau-phase cultures: an experimental model for identifying drugs which are
      bioactivated within the microenvironment of solid tumours.
AB  - A commonly used technique for evaluating potential bioreductive drugs is the
      determination of hypoxic cytotoxicity ratios in vitro. This experimental model,
      however, does not accurately mimic the tumour microenvironment, as other factors
      (such as reduced pH, poor nutrient status, low cell proliferation rates and high
      catabolite concentrations) are not incorporated into the design of the assay.
      Plateau-phase monolayer cultures possess many of these characteristics, and this
      study compared the response of plateau-phase and exponentially growing human
      colon carcinoma cells (DLD-1) with a series of standard and bioreductive
      compounds. All drugs tested were added directly to conditioned medium and three
      patterns of chemosensitivity were observed. In the case of doxorubicin,
      vinblastine and 5-fluorouracil, exponentially growing cells were significantly
      more responsive than plateau-phase cultures. ThioTEPA and MeDZQ (2,5-diaziridinyl
      1, 4-benzoquinone) were equally cytotoxic to both populations of cells.
      Tirapazamine (SR4233), RSU 1069, mitomycin C and EO-9, however, were
      preferentially toxic towards plateau-phase compared with exponentially growing
      cells. While the exact mechanisms responsible for these observations in each case
      are not known, this study suggests that plateau-phase cultures may prove to be a
      useful experimental model in the evaluation of drugs designed to work
      preferentially within the tumour microenvironment.

PMID- 9010027
TI  - Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.
AB  - The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment
      with serum vitamin D3-binding protein-derived macrophage-activating factor
      (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell
      carcinoma). The results show that DBPMAF can markedly enhance the curative effect
      of PDT. The most effective DBPMAF therapy consisted of a combination of
      intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively)
      administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative
      to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The
      DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The
      PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact
      hypersensitivity response in treated mice, was greatly reduced with the combined
      DBPMAF treatment. These observations suggest that the activation of macrophages
      in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour
      cures. As PDT not only reduces tumour burden but also induces inflammation, it is
      proposed that recruitment of the activated macrophages to the inflamed tumour
      lesions is the major factor for the complete eradication of tumours.

PMID- 9010028
TI  - Expression of the multidrug resistance-associated protein (MRP) gene in
      colorectal carcinomas.
AB  - To determine the clinical significance of MRP in patients with colorectal
      carcinomas, we have studied the expression of the MRP gene by reverse
      transcription-polymerase chain reaction (RT-PCR) (n = 105) and by
      immunohistochemistry (n = 30). MRP mRNA expression was observed in 92 (88%)
      tumour specimens. Positive MRP staining with monoclonal antibodies QCRL-1 and
      QCRL-3 was detected in all samples studied with strong staining in seven (23%)
      and weak staining in 23 (77%) specimens. Strong MRP staining in these samples did
      not appear to be related to the age and sex of the patients, localization of the
      primary tumour, histological grade, tumour size, lymph node metastasis, distant
      metastasis and tumour stage. Strong MRP staining was not associated with MDR1 RNA
      or P-glycoprotein (P-gp) expression. Kaplan-Meier curves revealed that overall
      survival of patients with strong MRP-staining tumours was similar to the survival
      of patients with weak-staining tumours. These data indicate that the MRP gene is
      expressed in primary colorectal carcinomas but is neither related to known
      prognostic factors nor a prognostic factor by itself.

PMID- 9010029
TI  - Growth inhibition of human lung adenocarcinoma cells by antibodies against
      epidermal growth factor receptor and by ganglioside GM3: involvement of receptor
      directed protein tyrosine phosphatase(s).
AB  - Growth of the EGF receptor-expressing non-small-cell lung carcinoma cell line
      H125 seems to be at least partially driven by autocrine activation of the
      resident EGF receptors. Thus, the possibility of an EGF receptor-directed
      antiproliferative treatment was investigated in vitro using a monoclonal antibody
      (alpha EGFR ior egf/r3) against the human EGF receptor and gangliosides which are
      known to possess antiproliferative and anti-tyrosine kinase activity. The
      moderate growth-inhibitory effect of alpha EGFR ior egf/r3 was strongly
      potentiated by the addition of monosialoganglioside GM3. Likewise, the
      combination of alpha EGFR ior egf/r3 and GM3 inhibited EGF receptor
      autophosphorylation activity in H125 cells more strongly than either agent alone.
      A synergistic inhibition of EGF receptor autophosphorylation by alpha EGFR ior
      egf/r3 and GM3 was also observed in the human epidermoid carcinoma cell line
      A431. In both cell lines, the inhibition of EGF receptor autophosphorylation by
      GM3 was prevented by pretreatment of the cells with pervanadate, a potent
      inhibitor of protein tyrosine phosphatases (PTPases). Also, GM3 accelerated EGF
      receptor dephosphorylation in isolated A431 cell membranes. These findings
      indicate that GM3 has the capacity to activate EGF receptor-directed PTPase
      activity and suggest a novel possible mechanism for the regulation of cellular
      PTPases.

PMID- 9010030
TI  - Laminin and collagen IV subunit distribution in normal and neoplastic tissues of
      colorectum and breast.
AB  - To invade and metastasize, carcinomas must penetrate or lose their epithelial
      basement membrane (EBM), and then penetrate basement membranes (BMs) surrounding
      blood vessels, lymphatics, nerves and muscle cells. Knowledge of the composition
      of different BMs is necessary, so that appropriate antibodies and DNA probes are
      used to analyse these events. Laminin and type IV collagen are the principal BM
      components. However, recent studies show these two proteins exist in various
      isoforms, each of which is a heterotrimer of different subunit polypeptides. In
      this study, we analysed the distribution of laminin subunits, alpha 1 (lam),
      alpha 2 (lam), beta 1(lam), beta 2(lam) and gamma 1 (lam), and collagen IV
      subunits, alpha 1(IV), alpha 3(IV), alpha 4(IV) and alpha 5 (IV), in normal and
      neoplastic tissues of colorectum and breast. Subunits alpha 1(IV), alpha 1(lam),
      beta 1(lam) and gamma 1(lam) were detected in all BMs, while the distribution of
      alpha 3(IV), alpha 4(IV), alpha 5(IV) and alpha 2(lam) was much more restricted.
      In carcinomas, EBM staining for all subunits was invariably discontinuous or
      absent, consistent with the presence of complete EBM breaks. Use of antibody to
      alpha 1(lam) selectively stained the EBMs of carcinomas. Strong vascular staining
      for alpha 1(lam), beta 1(lam), gamma 1(lam) and alpha 1(IV) suggests an abundance
      of BM proteins in vessel walls, which may aid tumour cell attachment before
      vascular invasion. Within carcinomas, vascular BM staining for beta 2(lam) was
      clearly weaker than in normal tissues, which may reflect incomplete maturation of
      these vessels.

PMID- 9010031
TI  - p53 alterations are predictive of chemoresistance and aggressiveness in ovarian
      carcinomas: a molecular and immunohistochemical study.
AB  - Chemotherapeutic management of ovarian cancers is a difficult task as these
      neoplasms show significant differences in chemosensitivity, even if they share
      identical clinicopathological features. The present study was undertaken to
      investigate the prognostic and predictive role of p53 alterations in ovarian
      cancer. To this end, using different technical approaches, i.e. genetic and
      immunohistochemical analyses, we analysed a series of 68 ovarian neoplasms
      including 15 low malignant potential (LMP) tumours and 53 invasive carcinomas. We
      never observed p53 abnormalities in LMP tumours. p53 alterations were present
      only in invasive ovarian carcinomas, and they were detected much more frequently
      in tumours characterized by high histological grade (P = 0.01) and advanced-stage
      disease (P = 0.006 and P = 0.05 for gene mutations and protein expression
      respectively). For 33 patients with invasive ovarian cancer, information was
      available concerning response to cisplatin-based chemotherapy. A strong
      correlation (P = 0.001) has emerged between p53 alterations and response to
      chemotherapy; only one (14%) of seven patients who had a pathological complete
      response to antiblastic drugs showed p53 aberrations, whereas 18 (82%) of 22
      cases with partial response and all of the four non-responsive patients scored
      positive for p53 abnormalities. We also observed that patients with p53 mutations
      had a significantly shorter progression-free survival than patients with p53
      negative tumours (P = 0.05). Taken together, our results strongly suggest that in
      epithelial ovarian malignancies tumours showing p53 aberrations are significantly
      less sensitive to chemotherapy and more aggressive than those with functional
      p53. Thus, a routine analysis of this gene could have profound implications for
      the treatment of ovarian cancer.

PMID- 9010032
TI  - 'Hepatoma-specific' alphafetoprotein may permit preclinical diagnosis of
      malignant change in patients with chronic liver disease.
AB  - The only hope for effective treatment of hepatocellular carcinoma (HCC or
      'hepatoma') lies in early diagnosis. Measurement of the serum alphafetoprotein
      (AFP) level is potentially a useful screening test. When grossly raised, it is
      almost diagnostic of HCC. However, modestly elevated levels may also arise in
      patients with benign chronic liver disease, and this markedly decreases the
      test's specificity and hence its clinical value. In 582 consecutive attendees at
      an outpatient clinic for people with chronic liver disease, a single blood sample
      was taken for analysis of 'total' AFP and the 'hepatoma-specific' AFP isoform.
      Using ultrasonography as the primary screening method, patients with AFP levels >
      or = 50 ng ml-1 were followed up throughout the study or until HCC was diagnosed
      on the basis of conventionally defined criteria. On entry into the study, 53
      patients had an AFP concentration > = or 50 ng ml-1 and the 'hepatoma-specific'
      AFP isoform was detected in 26 of these. During an 18-month follow-up period, a
      diagnosis of HCC was established by conventional methods in 19 (17 'definite' and
      two 'probable') of these 26 patients. In only two cases was there ultrasound
      evidence of tumour development at the time AFP was first found to be elevated; in
      the remainder a diagnosis of HCC, based on ultrasound screening, was established
      at a median time of 3.6 months (range 1-18 months) after entry into the study.
      Among those 27 without the 'hepatoma-specific' isoform, one developed a
      'definite' HCC and two developed 'probable' tumours. With the application of
      'hepatoma-specific' AFP, the positive predictive value of the test was 73.1%,
      compared with only 41.5% using the conventional 'total' AFP test. Application of
      this test for the 'hepatoma-specific' AFP markedly increases the positive
      predictive value of AFP and, in some cases, permits the presence of tumour to be
      inferred before it could be detected by routine ultrasound examination.

PMID- 9010033
TI  - Progression of familial adenomatous polyposis (FAP) colonic cells after transfer
      of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in
      invasion.
AB  - Little is known about the the signalling pathways driving the adenoma-to
      carcinoma sequence in human colonic epithelial cells. Accumulation and activation
      of the src tyrosine kinase in colon cancer suggest a potential role of this
      oncogene in this early progression. Therefore, we introduced either activated src
      (m-src), polyoma-MT alone or combined with normal c-src in the adenoma PC/AA/C1
      cell line (PC) to define the function and phenotypic transformations induced by
      these oncogenes in familial adenomatous polyposis (FAP) colonic epithelial cells.
      Functional expression of these oncoproteins induced the adenoma-to-carcinoma
      conversion, overexpression of the hepatocyte growth factor (HGF) receptor Met,
      but failed to confer invasiveness in vivo and in vitro, or to produce alterations
      in cell proliferation and differentiation. In contrast, PC-msrc cells became
      susceptible to the HGF-induced invasion of collagen gels and exhibited sustained
      activation of the pp60src tyrosine kinase and Tyr phosphorylation of the 120-kDa
      E-cadherin, which was further increased by HGF Transcripts of HGF were clearly
      identified by reverse transcription-polymerase chain reaction (RT-PCR) and
      Southern blot in the parental and transformed PC cells, suggesting an autocrine
      mechanism. Taken together, the data indicate that: (1) experimental activation of
      src and PyMT pathways directly induces tumorigenicity and Met upregulation in a
      colon adenoma cell line; (2) HGF-activated Met and src cooperate in inducing
      invasion; (3) in view of the molecular associations between catenins and cadherin
      or the tumour-suppressor gene product APC, the cell adhesion molecule E-cadherin
      may constitute a downstream effector of src and Met.

PMID- 9010035
TI  - Five newly established oesophageal carcinoma cell lines: phenotypic and
      immunological characterization.
AB  - The derivation of permanent cell lines from 40 resected oesophageal carcinomas
      has been attempted. Five long-term lines have been established from three
      adenocarcinomas, one mixed carcinoma and one squamous carcinoma. Molecular and
      cellular analyses have been carried out on the lines and clones derived from
      them. Karyotype analysis indicates genetic variation among the clones. HLA-A, -B
      and -C is expressed constitutively, but not HLA-DR. ICAM-1-expressing phenotypes
      may have arisen during adaptation to long-term culture. All lines are capable of
      response to interferon-gamma (IFN-gamma) and all produce transforming growth
      factor beta 1 (TGF-beta 1). Two lines are resistant to the inhibitory growth
      effects of the latter, possibly contributing to malignancy. It is anticipated
      that these lines, originating from histologically different carcinomas, will
      provide a valuable, continuous resource for the investigation and treatment of
      these aggressive tumours.

PMID- 9010034
TI  - Type I insulin-like growth factor receptor gene expression in normal human breast
      tissue treated with oestrogen and progesterone.
AB  - The epithelial proliferation of normal human breast tissue xenografts implanted
      into athymic nude mice is significantly increased from basal levels by oestradiol
      (E2), but not progesterone (Pg) treatment at serum concentrations similar to
      those observed in the luteal phase of the human menstrual cycle. Type I IGF
      receptor (IGFR-I) mRNA and protein have been shown to be up-regulated by E2 in
      MCF-7 breast cancer cells in vitro in which IGF-I and E2 act synergistically to
      stimulate proliferation. We have investigated the expression of the IGFR-I mRNA
      in normal human breast xenografts treated with or without E2 or Pg alone and in
      combination. Northern analysis of 20 micrograms of RNA extracted from the breast
      xenograft samples showed no hybridization with 32P-labelled IGFR-I probe,
      although an 11-kb species of IGFR-I mRNA could be seen when 20 micrograms of RNA
      extracted from either MCF-7 breast cancer cells or human breast carcinomas was
      examined in this way. In order to analyse the expression of IGFR-I mRNA in breast
      xenografts, a quantitative reverse transcription-polymerase chain reaction (RT
      PCR) was employed in which RNA loading, reverse transcription and PCR
      efficiencies were internally controlled. The data indicate that the IGFR-I mRNA
      is up-regulated by two to threefold compared with untreated levels by 7 and 14
      days E2 treatment. In contrast, 7 or 14 days Pg treatment down-regulates the
      receptor mRNA to approximately half that of untreated levels, whereas combination
      E2 and Pg treatment produced a twofold increase in IGFR-I mRNA levels compared
      with untreated tissue. The results are consistent with the suggestion that E2 may
      act to stimulate proliferation indirectly via a paracrine mechanism involving
      IGFs in normal as well as malignant human breast epithelial cells.

PMID- 9010036
TI  - Localization of a breast cancer tumour-suppressor gene to a 3-cM interval within
      chromosomal region 16q22.
AB  - Allelic losses on chromosome 16q in tumour cells are frequent in a variety of
      malignancies, suggesting the presence of one or more tumour-suppressor genes in
      the region. Among 210 sporadic breast cancers we examined using 15 microsatellite
      markers on the long arm of chromosome 16, heterozygosity for at least one locus
      was lost in 141 (67%). Detailed deletion mapping revealed two distinct commonly
      deleted regions. One region was defined as a 3-cM interval flanked by markers
      D16S512 and D16S515 at 16q22; the second consisted of a 9.5-cM interval flanked
      by markers D16S498 and D16S303 at q24.3. Allelic loss on 16q was observed
      frequently in small tumours, tumours without lymph node metastasis and tumours of
      the non-invasive histological type as well as in tumours of more advanced
      phenotype, suggesting that inactivation of one of at least two tumour-suppressor
      genes on 16q plays a role in early stage breast carcinogenesis.

PMID- 9010037
TI  - Spontaneous overexpression of the long form of the Bcl-X protein in a highly
      resistant P388 leukaemia.
AB  - A novel resistant variant of murine P388 leukaemia, P388/SPR, was identified by
      de novo resistance to doxorubicin (DOX) in vivo. This mutant displayed a similar
      level of cross-resistance to etoposide (VP-16) and other topoisomerase II (topo
      II) inhibitors. Further analysis of the phenotype revealed a broad cross
      resistance to vinca alkaloids, alkylating agents, antimetabolites, aphidicolin
      and UV light. Low-level expression of mdr1 and P-glycoprotein (P-gp), as well as
      a modest impairment of cellular drug accumulation and partial reversion of
      resistance to DOX and VP-16 by cyclosporine, confirmed a moderate role of P-gp in
      conferring drug resistance in P388/SPR cells. Consistent changes in neither topo
      II expression or activity nor glutathione metabolism could be detected. Induction
      of apoptosis was significantly reduced in P388/SPR cells, as indicated by minimal
      DNA fragmentation. Analysis of oncogenes regulating apoptotic cell death revealed
      a marked decrease of bcl-2 in combination with a moderate reduction of bax
      protein, but a striking overexpression of the long form of the bcl-X protein.
      Transfection of human bcl-X-L into P388 cells conferred drug resistance similar
      to that of P388/SPR cells. The data suggest that overexpression of bcl-X-L
      results in an unusual phenotype with broad cross-resistance to non-MDR-related
      cytotoxins in vitro, and provide an interesting example of spontaneous
      overexpression of another member of the bcl-2 gene family in cancer.

PMID- 9010038
TI  - Identification of genetic changes associated with drug resistance by reverse in
      situ hybridization.
AB  - The molecular cytogenetic techniques of comparative genomic hybridization (CGH)
      and reverse in situ hybridization (REVISH) allow the entire genomes of tumours to
      be screened for genetic changes without the requirement for specific probes or
      markers. In order to define the ability of REVISH to detect and map regions of
      amplification associated with drug resistance, we investigated a panel of cell
      lines selected for resistance to doxorubicin and intrinsic sensitivity to
      topoisomerase II-inhibitory drugs. We have defined a modified REVISH protocol,
      which involves double hybridizations with genomic DNA from the test cell lines
      and chromosome-specific whole chromosome paints to identify the chromosomes to
      which the amplicons localize. Sites of amplification are then mapped by
      fractional length measurements (Flpter), using published genome databases. Our
      findings show that amplification of the topoisomerase II alpha gene is readily
      detected and mapped, as is amplification of the MDR and MRP loci. Interestingly,
      REVISH detected a new amplicon in the doxorubicin-resistant lung cancer cell
      line, GLC4-ADR, which mapped to chromosome 1q. REVISH is therefore ideally suited
      to characterize genetic changes specific for drug resistance within a background
      of genetic anomalies associated with tumour progression.

PMID- 9010039
TI  - Correlation between clinical response to interleukin 2 and HLA phenotypes in
      patients with metastatic renal cell carcinoma.
AB  - HLA phenotypes were characterized for 79 patients with metastatic renal cell
      carcinoma treated with interleukin 2 (IL-2). HLA-A32 was associated with a
      clinical response (P = 0.025). The frequency of HLA-A3 and/or A32 was higher
      among responders than non-responders (P = 0.008). Thus, these results suggest
      that, in vivo, IL-2 may enhance cellular-mediated immunity against a tumour
      antigen and that some MHC molecules are more efficient than others for endogenous
      tumour antigen presentation.

PMID- 9010040
TI  - A clinical and pharmacokinetic study of the combination of carboplatin and
      paclitaxel for epithelial ovarian cancer.
AB  - The aim of this phase I study was to determine the maximum tolerated dose of a 3
      h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1
      min every 4 weeks for up to six cycles and to evaluate any possible
      pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were
      treated with paclitaxel followed by a 30-min infusion of carboplatin. Paclitaxel
      dose was escalated from 150 mg m-2 to 225 mg m-2 in cohorts of three patients.
      Carboplatin dose was based on renal function. Pharmacokinetic studies were
      performed in nine patients (at least two at each dose level). A total of 66
      courses were evaluable for assessment. Grade 3 or 4 neutropenia was seen in 70%
      of the courses, however hospitalization was not required. Grade 3 or 4
      thrombocytopenia occurred in 24% of the courses. Alopecia, myalgia and peripheral
      neuropathy were common but rarely severe. The pharmacokinetics of paclitaxel was
      non-linear and did not appear to be influenced by co-administration of
      carboplatin. The AUC of carboplatin was 7.0 +/- 1.4 mg ml-1 min, indicating that
      there was no pharmacokinetic interaction. The combination of carboplatin and
      paclitaxel may be administered as first-line treatment for advanced ovarian
      cancer. Although myelosuppression is the dose-limiting toxicity of the component
      drugs, the severity of thrombocytopenia was less than anticipated. The results of
      this study, with only a small number of patients, need to be confirmed in future
      investigations.

PMID- 9010041
TI  - Dose-response study of ibandronate in the treatment of cancer-associated
      hypercalcaemia.
AB  - Hypercalcaemia is an important cause of morbidity in malignant disease. We
      studied the efficacy and safety of intravenous ibandronate (a new, potent
      bisphosphonate) in a multicentre study of 147 patients with severe cancer
      associated hypercalcaemia which had been resistant to treatment with rehydration
      alone. Of 131 randomized patients who were eligible for evaluation, 45 were
      allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42
      patients to receive 6 mg. Serum calcium values fell progressively in each group
      from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was
      maintained for up to 36 days after treatment. The 2-mg dose was significantly
      less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the
      number of patients who achieved serum calcium values below 2.7 mM after treatment
      was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the
      6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three
      factors were found to predict response; ibandronate dose (higher doses were more
      effective), severity of presenting hypercalcaemia (severe hypercalcaemia was
      associated with less complete response) and tumour type (patients with breast
      carcinoma and haematological tumours responded better than those with other
      tumours). Ibandronate was generally well tolerated and no serious drug-related
      adverse events were observed. We conclude that ibandronate is a safe, well
      tolerated and effective treatment for cancer-associated hypercalcaemia, which
      should prove a useful addition to the current range of therapies available to
      treat this condition.

PMID- 9010042
TI  - Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II
      and III breast cancer.
AB  - Two hundred and eleven patients with node-positive stage II and III breast cancer
      were treated with eight cycles of adjuvant chemotherapy comprising
      cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without
      tamoxifen. All patients had undergone radical surgery, and 148 patients were
      treated with post-operative radiotherapy in two randomized studies. The impact of
      haematological toxicity of CAFt on distant disease-free (DDFS) and overall
      survival (OS) was recorded. Dose intensity of all given cycles (DI), dose
      intensity of the two initial cycles (DI2) and total dose (TD) were calculated
      separately for all chemotherapy drugs and were correlated with DDFS and OS.
      Patients with a lower leucocyte nadir during the chemotherapy had significantly
      better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two
      first cycles also correlated significantly with DDFS (P = 0.05) in univariate but
      not in multivariate analysis, while the leucocyte nadir retained its prognostic
      value. These results indicate that the leucocyte nadir during the adjuvant
      chemotherapy is a biological marker of chemotherapy efficacy; this presents the
      possibility of establishing an optimal dose intensity for each patient. The
      initial dose intensity of adjuvant chemotherapy also seems to be important in
      assuring the optimal effect of adjuvant chemotherapy.

PMID- 9010044
TI  - Clinical manifestations of diffuse idiopathic skeletal hyperostosis (DISH)

PMID- 9010043
TI  - CODE chemotherapy with and without granulocyte colony-stimulating factor in small
      cell lung cancer.
AB  - Sixty-three patients with extensive-stage small-cell lung cancer were randomized
      to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE)
      alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG
      CSF). rhG-CSF administration in support of CODE chemotherapy resulted in
      increased mean total received dose intensity for all drugs (P = 0.03) with a
      significant improvement in survival (P = 0.004).

PMID- 9010045
TI  - Diagnostic criteria for work-related upper limb disorders.

PMID- 9010046
TI  - The Michael Mason Prize Essay 1996. Role of adhesion mechanisms in the
      pathogenesis of chronic synovitis.
AB  - The hallmark of many rheumatic conditions, including rheumatoid arthritis (RA)
      and other seronegative inflammatory arthropathies (OIA), is a persistent
      inflammatory process that mainly affects synovial joints. Although the aetiology
      of the synovitis remains elusive, the pathogenesis is thought to be immune
      mediated. There are several reasons to believe that synovial T lymphocytes (S-TL)
      play a central role both as regulatory and effector cells in the initiation and
      perpetuation of the inflammatory process. In early studies, we demonstrated that
      the majority of S-TL are of the CD45RO 'memory' phenotype, while CD45RA 'naive' T
      cells are virtually absent. Various mechanisms can be responsible for such
      preferential accumulation. In this dissertation, I will present a number of
      studies, carried out over several years, investigating the relative role of
      adhesion and migration in the pathogenesis of the CD45RO accumulation in inflamed
      tissues. Since the first step in lymphocyte extravasation is adhesion to
      endothelium, the ability of purified CD45RO vs CD45RA T cells to adhere to human
      umbilical vein endothelial cells (HUVEC) in vitro was analysed. Second, to
      examine the migration process itself, an in vivo model of cell migration into
      suction-induced skin blisters raised over delayed-type hypersensitivity reactions
      was developed. Third, the role of tissue-specific homing mechanisms in the
      regulation of T-cell migration into different inflammatory sites was
      investigated. Finally, the adhesion of T cells to extracellular matrix (ECM)
      components, as a mechanism for preferential cell retention in inflamed tissues,
      was examined. These studies demonstrate that the critical mechanisms leading to
      CD45RO lymphocyte accumulation in chronic inflammatory foci include (a) an
      increased adhesion to endothelium, (b) an increased migratory capacity and (c) an
      increased adhesion to ECM components. I also present evidence to suggest that
      besides these general mechanisms, organ-specific homing may be of relevance in
      determining the selective accumulation of distinct CD45RO T cells in different
      inflamed tissues.

PMID- 9010047
TI  - DNA allelic alterations within VNTR loci of scleroderma families.
AB  - We have characterized genetic alterations at the molecular level in 49
      scleroderma and 45 control families using variable number tandem repeats (VNTRs).
      Additionally, paired fibroblast cell lines from the 'affected' and 'unaffected'
      skin and peripheral blood leucocytes of 30 patients were also examined. All
      families in this study were typed for Class I Cw alleles and Class II-DRB, -DQA
      and -DQB to confirm family membership. There were significant rises in the level
      of VNTR mutations in scleroderma patients (36.7%, n = 18), their siblings (16.3%,
      n = 13) and offspring (21.7%, n = 15). The level of VNTR mutations in the control
      group was 0.6% (n = 5). These mutations did not correlate with the presence of
      autoantibodies and no patient was taking a known clastogenic drug. The most
      common VNTR site for mutation was pYNZ22 (17p13.4). Differences were also seen in
      the VNTR alleles between fibroblast and lymphocyte DNA from the same patient, as
      measured by size alteration of one of the alleles. We have found that VNTRs are
      unstable in scleroderma patients, relatives and offspring. The reason for the
      genomic changes remains unknown, but previous studies have implicated the
      presence of a clastogen.

PMID- 9010048
TI  - T-cell receptor repertoire of infiltrating T cells in lachrymal glands, salivary
      glands and kidneys from alymphoplasia (aly) mutant mice: a new model for
      Sjogren's syndrome.
AB  - Alymphoplasia (aly) mice are thought to provide a new model for systemic
      Sjogren's syndrome (SS), since they reveal remarkable infiltration of mononuclear
      cells into salivary glands, lachrymal glands and kidneys, and show histological
      findings similar to those in patients with SS. Cell transfer experiments
      demonstrate that T cells induce the infiltration of mononuclear cells into
      several tissues in aly mice. To analyse the pathogenesis of cell infiltration in
      various tissues, we examined T-cell receptor (TCR) V beta usage of T cells in
      salivary glands, lachrymal glands and kidneys from aly mice, using family
      polymerase chain reaction (PCR) and PCR-single-strand conformation polymorphism
      (SSCP) methods. The results of SSCP demonstrated that the infiltrating T cells in
      the three organs expanded clonally, suggesting that they proliferate by antigen
      driven stimulation. Some TCR V beta genes (V beta 1, 3, 6, 11, 12, 16) were
      commonly used in salivary glands, lachrymal glands and kidneys, while the V beta
      7 gene was specifically expressed in kidneys. SSCP also showed that there were a
      few shared T-cell clones (V beta 3- and V beta 6-positive cells) among the three
      tissues. Indeed, sequence analysis of accumulated T cells showed that a conserved
      amino acid (leucine) at position 98 in the TCR V beta complementary determining
      region (CDR) 3 was detected in all organs at high frequency (41-57%) and the
      amino acid sequence motif (LG) was specifically conserved at a frequency of 32%
      in the three organs. In conclusion, T cells that infiltrate into lachrymal
      glands, salivary glands and kidneys of aly mutant mice might recognize shared
      common epitopes in all three organs and a kidney-specific antigen.

PMID- 9010049
TI  - Further characterization of anti-endothelial cell antibodies in systemic lupus
      erythematosus by controlled immunoblotting.
AB  - Anti-endothelial cell antibodies in systemic lupus erythematosus were further
      characterized by controlled immunoblotting studies with EN4 defined membrane and
      cytosol preparations of human umbilical vein endothelial cells. Antibodies to
      endothelial cell membranes, some of which reacted with the membranes of both
      dermal fibroblasts and T-cell lymphoma HUT78, were detected in 26/33 patients
      (78%), but in only 4/34 normal controls (P < 0.001) and 3/11 patients with a
      recent myocardial infarction. Although the antibody response was very
      heterogeneous against epitopes ranging from 17 to 205 kDa, there was a tendency
      to detect particular membrane epitopes at 31-33 kDa (15 cases), 72-78 kDa (eight
      cases), 66-68 kDa (seven cases) and 17-19 kDa (five cases). No correlations
      between antibodies to particular epitopes and disease manifestations were
      observed nor was a relationship to disease activity detected in a retrospective
      analysis. However, the possibility that anti-endothelial cell antibodies may be
      pathogenically important was supported by prospective serial studies in two cases
      with nephritis who showed diminution and disappearance of anti-endothelial cell
      antibodies as their active disease was treated into remission.

PMID- 9010050
TI  - Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with
      antiphospholipid syndrome.
AB  - The clinical significance of anti-beta 2 glycoprotein I (beta 2-GPI) antibodies
      was evaluated in patients with antiphospholipid syndrome (APS), primary and
      secondary to systemic lupus erythematosus (SLE). Anti-beta 2-GPI were tested in
      120 patients (39 primary APS, 32 APS with SLE and 49 SLE without APS) by ELISA
      utilizing irradiated plates in the absence of cardiolipin. Anticardiolipin
      antibodies (aCL) and antiphosphatidylserine antibodies were also measured in the
      same patients using standardized assays. Anti-beta 2-GPI titres correlated
      strongly to those of aCL (r = 0.816, P = 0.0001), and to those of
      antiphosphatidylserine antibodies (r = 0.841, P = 0.0001). Anti-beta 2-GPI were
      detected in 53.5% of APS patients (38/71), but only in 4.1% of SLE patients
      without APS (2/49). In the latter group, 24.5% (12/49) of patients had a positive
      titre of aCL. The anti-beta 2-GPI assay showed higher specificity for APS than
      the aCL in APS (96 vs 75%, respectively, chi 2 = 6.75, P = 0.00094). Our findings
      suggest that the assay of anti-beta 2-GPI may improve the specificity for APS.

PMID- 9010051
TI  - Synovial fluid interleukin-8 and neutrophil function in rheumatoid arthritis and
      seronegative polyarthritis.
AB  - The relationships between synovial fluid (SF) interleukin-8 (IL-8) and neutrophil
      turnover as measured by cytidine deaminase (CD), and SF metabolites were studied
      in 28 patients, 16 with rheumatoid arthritis (RA; median age and disease duration
      62 and 14 yr, respectively) and 12 with seronegative polyarthritis (SNP; median
      age and disease duration 32 and 5 yr, respectively). Knee SF samples were
      aspirated using indwelling cannulae following a period of rest for 1 h. SF IL-8
      levels (measured by an ELISA) were significantly elevated in RA compared to SNP
      (median 2.35 vs 0.22 ng/ml, P < 0.001), as were median levels of CD (55.8 vs 8.11
      U/ml, P < 0.01), lactic acid (29.6 vs 16.6 mg/dl, P < 0.001), glucose (57.9 vs
      84.5 mg/dl, P < 0.05) and the lactate to glucose ratio (0.85 vs 0.19, P < 0.001).
      Measures of disease activity, C-reactive protein, plasma viscosity and articular
      index were also elevated in RA compared to SNP (P < 0.05). SF IL-8 levels
      correlated strongly with CD, lactate, glucose and the lactate to glucose ratio
      when both disease groups were considered together (P < 0.001). These parameters
      also showed some association with the measures of disease activity (P < 0.05).
      All these associations were less marked when the individual disease groups were
      analysed separately. These results suggest that factors responsible for
      neutrophil accumulation and priming (probably IL-8) are present in SF, and these
      coincide with products of their activation (CD). The degree of neutrophil
      turnover is linked to the anaerobic metabolism of the synovial cavity.

PMID- 9010052
TI  - Large granular lymphocyte expansions in Felty's syndrome have an unusual
      phenotype of activated CD45RA+ cells.
AB  - One-third of patients with Felty's syndrome (FS) have significant clonal
      expansions of CD3+ CD8+ large granular lymphocytes (LGLs) in their peripheral
      blood. The reasons for this are unclear, but one hypothesis is that they are
      activated antigen-specific cells of pathogenic relevance. Cytofluorographic
      analysis of activation markers demonstrated that the cell surface phenotype of
      these expansions was CD57+, HLA-DR+, IL-2R-, Leu-8+, CD69+, LFA-1+, ICAM-1+, VLA
      4+, i.e. 'activated' T cells. However, they also expressed the phenotype CD45RA+,
      CD45RBbright, CD45RO-, usually associated with 'naive' cells. This could result
      from aberrant activation, malignant transformation or from a 'reversal' of CD45
      phenotype following chronic antigenic stimulation. In three patients with RA and
      non-clonal LGL expansions, a more variable phenotype was found. In one of these
      patients, the expanded population was identified in the peripheral blood, but not
      the synovial fluid. This may suggest that, at least in this individual, any
      pathogenic effect is exerted systemically.

PMID- 9010053
TI  - Clinical associations of dual-energy X-ray absorptiometry measurement of hand
      bone mass in rheumatoid arthritis.
AB  - Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry
      (DXA) has potential as a marker of progression in early rheumatoid arthritis
      (RA). We examined a DXA methodology and studied in a cross-sectional manner 202
      patients with RA. Hand BMD correlated inversely with age and was higher in males.
      Hand BMD correlated with lumbar and femoral sites. In females, BMD of the hand
      correlated positively with grip strength and negatively with disability. Those
      with higher C-reactive protein (CRP) had significantly lower hand BMD than those
      with normal CRP. In patients with a normal CRP, the hand BMD:lumbar BMD ratios
      were significantly higher in patients with longer disease duration. Hand BMD
      correlates with measures of disease activity, functional capacity and also with
      lumbar and femoral BMD. Hand bone loss occurs in early disease, in the absence of
      detectable systemic disease, and before lumbar BMD loss. It has the potential to
      be an outcome measure in early disease.

PMID- 9010054
TI  - Clinical improvement and radiological deterioration in rheumatoid arthritis:
      evidence that the pathogenesis of synovial inflammation and articular erosion may
      differ.
AB  - The contrast between clinical improvement and radiological deterioration in
      rheumatoid arthritis (RA) is striking. We characterized this relationship using
      serial disease activity measures and radiographs of hands and feet in 40 RA
      patients observed over 6 yr. All disease activity measures improved, including
      grip strength, Ritchie index (RI), haemoglobin and erythrocyte sedimentation rate
      (ESR) (all P < 0.0001). In contrast, articular erosion increased (P < 0.0001).
      Radiological change during the study correlated with RI (r = 0.49), haemoglobin
      (r = -0.56) and ESR (r = 0.53). Radiological status at review also correlated
      with these variables (r = 0.36, -0.44 and 0.36, respectively). Articular erosion
      continues in RA despite clinical improvement and is accelerated in those with
      evidence of continuing synovial inflammation, reflected in clinical and
      laboratory measures of disease activity. Since many therapies in RA suppress
      inflammation, but not erosion, these findings suggest that the pathogenesis of
      articular erosion may differ from that of synovial inflammation.

PMID- 9010055
TI  - The value of SPECT scans in identifying back pain likely to benefit from facet
      joint injection.
AB  - Lumbar facet disease is sometimes implicated in low back pain. Identification is
      difficult and this may account for a variable response. Single photon emission
      computerized tomography (SPECT) is a scanning technique which enables
      localization of facet joint pathology. We determined whether recognition of facet
      disease by this method improved the response to corticosteroid injection
      treatment. Fifty-eight patients with low back pain and displaying accepted
      clinical criteria for facet joint disease were evaluated by SPECT. Twenty-two had
      facetal uptake of isotope. These and the tender facet joints of 36 scan-negative
      patients were injected with 40 mg methylprednisolone and 1 ml 1% lignocaine under
      X-ray control. Pain was assessed by a blind observer using the McGill
      questionnaire (MGQ), Present Pain Intensity score (PPI) and a Visual Analogue
      Scale (VAS). VAS, PPI and MGQ were reduced in the scan-positive patients at 1
      month (P = 0.05, P = 0.0005, P = 0.005) and MGQ at 3 months (P = 0.01), whilst
      scan-negative patients were unchanged. The percentage of scan-positive patients
      who reported improvement was 95% at 1 month and 79% at 3 months, significantly
      greater than the control group (P = 0.0005, P = 0.01). Within 6 months, pain
      improvement in the SPECT-positive group was no longer statistically significant.
      Tenderness did not correlate with increased uptake on SPECT scan. Osteoarthritis
      of the facets was more common in the SPECT-positive patients (P < 0.001), but did
      not correspond with sites of increased uptake on SPECT scan. These results
      suggest that SPECT can enhance the identification of back pain sufferers likely
      to obtain short-term benefit from facet joint injection.

PMID- 9010056
TI  - Video image analysis of hands: development of an 'anatomic index' as a potential
      outcome measure in rheumatoid arthritis.
AB  - In this study, we used video image analysis for the measurement of hand
      dimensions to reflect destructive changes in rheumatoid arthritis. Thirteen
      dimensions were measured from anteroposterior and lateral views of the hands,
      open and closed. Comparison of measurements in 19 patients and 19 control
      subjects showed significant differences for nine of the 13 measurements. Five
      were reproducible on retesting in a subset of patients and normals. Two were
      eliminated because they were similar to other measurements. The three remaining
      measurements selected for differentiation of patients and normals, and
      reproducibility, were combined in an arbitrary 'anatomic index'. This enhanced
      separation of normals and patients with rheumatoid arthritis. The results
      demonstrate that measurement of certain hand dimensions and their combination in
      an 'anatomic index' could provide a measure reflecting the progressive anatomical
      abnormality caused by rheumatoid arthritis. Validation of this concept could
      provide a further outcome measure in patients with rheumatoid arthritis.

PMID- 9010057
TI  - Non-invasive assessment of vascular reactivity in forearm skin of patients with
      primary Raynaud's phenomenon and systemic sclerosis.
AB  - We have non-invasively assessed neurovascular control mechanisms in forearm skin
      of 10 healthy control subjects, eight patients with primary Raynaud's phenomenon
      (PRP) and 10 patients with systemic sclerosis (SSc) by iontophoresing
      acetylcholine (endothelial dependent), sodium nitroprusside (endothelial
      independent) and adrenaline, and measuring subsequent blood flow responses by
      dual-channel laser Doppler. Because basal forearm blood flow is low, adrenaline
      response was assessed by attenuation of reperfusion hyperaemia following 60 s of
      upper arm occlusion. Reperfusion hyperaemia prior to adrenaline iontophoresis
      differed significantly between groups (F2.21 = 4.3, P = 0.03), being lowest in
      the SSc and highest in the PRP group. However, the degree of attenuation of this
      hyperaemia by adrenaline did not differ between groups and all groups
      demonstrated similar vasodilatory responses to acetylcholine and to sodium
      nitroprusside. These findings may reflect that abnormalities in vascular tone in
      patients with Raynaud's phenomenon are local to the digits, or that vasoactive
      agents not examined in this study play a key role.

PMID- 9010058
TI  - Incidence of psoriatic arthritis in Finland.
AB  - Patients with psoriasis have an increased incidence of arthritis. Information on
      the incidence of psoriatic arthritis (PsA) is sparse. The present study covered
      those subjects who were entitled under the nationwide sickness insurance scheme
      to receive specially reimbursed medication for PsA in 5/21 central hospital
      districts in Finland (population basis approximately 1 million adults) in 1990. A
      total of 65 incident cases satisfied the concept of PsA. The annual incidence of
      PsA was 6/100,000 of the adult population (> or = 16 yr of age). The mean age at
      diagnosis was 46.8 yr. The peak incidence occurred in the 45-54 yr age group. The
      male to female ratio was 1.3:1. The incidence rate in the present study is in
      agreement with the sparse former figures, but age-specific incidence figures
      which have not been published earlier are also presented.

PMID- 9010059
TI  - Osteoarthritis of the hands in early populations.
AB  - A study of the distribution of osteoarthritis of the hands was carried out in a
      series of 168 skeletons (77 males, 87 females, four unknown sex) from
      archaeological sites in England. There were substantial differences in the
      distribution of the disease between the sexes, but the only significant
      differences between the hands were shown for the second and third
      metacarpophalangeal joints, which were more often affected on the right side. In
      the males, the disease was predominantly unifocal (in 45 of the 77 cases), but in
      the females it was predominantly multifocal (56 of the 87 cases). Where only a
      single joint was affected, it was most often the first carpometacarpal joint in
      females, whereas in males, this joint and the first metacarpophalangeal joints
      were equally likely to be involved. Single-linkage cluster analysis showed that
      the strongest link in males was between the trapezoscaphoid and
      trapezoidoscaphoid joints; in the females, the strongest links were between the
      first carpometacarpal, the distal interphalangeal and the first
      metacarpophalangeal joints.

PMID- 9010061
TI  - Is rheumatoid arthritis becoming a milder disease? Or are we starting second-line
      therapy in patients with milder disease?
AB  - The aim of the study was to see whether rheumatoid arthritis (RA) is becoming a
      milder disease. Information on the initial disease activity and patient function
      (modified Health Assessment Questionnaire-HAQ) was collected in all RA patients
      enrolled into studies of sulphasalazine since 1980 in two Glasgow teaching
      hospitals. Patients (352) were enrolled in trials in the decade 1980-1989, and
      were compared to 374 patients enrolled in 1990-1994. Patients recruited in the
      1980s were significantly younger, but had a similar disease duration to the 1990s
      patients. The 1980s patients had more active disease as measured by erythrocyte
      sedimentation rate (61 vs 44, P < 0.0001) and C-reactive protein (40 vs 26, P <
      0.0001), and significantly worse function (HAQ 2.3 vs 1.9, P < 0.001). The
      response to sulphasalazine was very similar in the two cohorts, in terms of the
      percentage of patients remaining on therapy for 6 months, and the percentage
      improvement in measures of disease activity. Patients with milder disease were
      enrolled into the more recent trials of sulphasalazine. This may be because RA is
      becoming a milder disease, but other possible explanations are discussed.

PMID- 9010060
TI  - The association between osteoarthritis and osteoporotic fracture: the Chingford
      Study.
AB  - Studies of the association between the presence of osteoarthritis (OA) and the
      risk of osteoporotic fractures have produced conflicting results. To address this
      question further, we have examined the association between self-reported,
      validated fractures and radiological OA at multiple sites in a large population
      of normal Caucasian women aged 45-65 yr. Despite having increased bone mineral
      density (BMD) of 5.3%, subjects with hip OA had a significantly increased risk of
      fracture [odds ratio (OR) 2.38, 95% CI 1.06-5.35] compared to controls. Subjects
      with lumbar spine OA, however, had a significantly reduced risk of fracture (OR
      0.45, 95% CI 0.23-0.80) compared to controls. This association was not explained
      by differences in BMD, weight, sex hormones or physical activity. No clear
      association was seen with fracture for hand or knee OA. These data suggest that
      the increased risk of fracture in subjects with OA of the hip is most likely to
      be due to mechanical and locomotor factors, such as the risk of falling.

PMID- 9010062
TI  - Lupus or lupoid hepatitis with mesenteric vasculitis.
AB  - A 15-yr-old girl with lupus presented with hepatitis and later a mesenteric
      vasculitis requiring bowel resection. The gastroenterological manifestations of
      lupus are reviewed with particular reference to hepatic involvement.

PMID- 9010063
TI  - Rheumatology and dermatology: sister specialities in Italy and Malta.

PMID- 9010064
TI  - The arthritis of coeliac disease: prevalence and pattern in 200 adult patients.
AB  - Arthritis has often been alluded to as an extra-intestinal clinical manifestation
      of coeliac disease, but definitive data regarding its prevalence are still
      lacking. We therefore evaluated the overall prevalence of articular involvement
      in 200 consecutive adult coeliac patients attending routine gastroenterology
      follow-up and in 40 controls, and determined whether the prevalence and pattern
      of articular involvement varied according to the dietary status. An arthritis was
      present in 26% of patients and in 7.5% of controls, prevalences ranging from 41%
      in patients on a regular diet to 21.6% in patients on a gluten-free diet (P <
      0.005). Arthritis was peripheral in 19 patients, axial in 15 and an overlap of
      both in 18 subjects. These data suggest that arthritis is much more common than
      previous reports have indicated, particularly in patients receiving an
      appropriate dietary regimen, and support the need for combined gastrointestinal
      and rheumatological follow-up in coeliac patients.

PMID- 9010065
TI  - Spinal pseudoarthrosis complicating ankylosing spondylitis: a report of two
      patients.
AB  - Two middle-aged men with long-standing ankylosing spondylitis presented with
      recurrence of back symptoms after minor traumas. Clinical and radiographic
      findings were suggestive of spinal pseudoarthrosis at the L2/L3 and T11/T12
      level, respectively, but the possibility of infectious spondylitis remained a
      concern. On granulocyte scintigraphy, the affected regions were distinguished by
      showing decreased activity. Magnetic resonance imaging clearly demonstrated the
      extent of the lesions and, in one of the patients, revealed spinal canal
      compression, which necessitated surgical treatment. The other patient gradually
      improved on conservative therapy.

PMID- 9010066
TI  - The 1994-5 Michael Mason Travelling Fellowship: goodbye the Commonwealth, hello
      Australia!!

PMID- 9010067
TI  - Antinuclear and antinucleolar antibodies in patients with scleroderma
      polymyositis overlap syndrome.

PMID- 9010068
TI  - Antineutrophil cytoplasmic antibody-positive polyarthritis associated with
      minocycline therapy.

PMID- 9010069
TI  - Antibody levels to Clostridium perfringens and response to sulphasalazine.

PMID- 9010070
TI  - ANCA in RA patients.

PMID- 9010071
TI  - Treatment of gout following cardiac transplantation.

PMID- 9010072
TI  - Combination therapy of anti-CD4 and anti-IL6 monoclonal antibodies in a case of
      severe spondylarthropathy.

PMID- 9010073
TI  - Cyclosporin A in the long-term treatment of psoriatic arthritis.

PMID- 9010074
TI  - New NSAIDs--inhibitors of cyclooxygenase 2--and renal damage.

PMID- 9010075
TI  - Subarachnoid haemorrhage secondary to ruptured cerebral aneurysm in a patient
      with osteogenesis imperfecta.

PMID- 9010076
TI  - Polyarteritis nodosa presenting as ischaemic colitis.

PMID- 9010077
TI  - Multiple cryptococcal brain abscesses in systemic lupus erythematosus.

PMID- 9010078
TI  - School Christmas shows ... 'look out the backache is behind you'.

PMID- 9010080
TI  - MRI in the assessment of synovium and cartilage.

PMID- 9010081
TI  - Clinical and laboratory assessments in rheumatoid arthritis and osteoarthritis.
AB  - Clinical and laboratory assessments in rheumatoid arthritis and osteoarthritis
      precede imaging methods in both defining diagnosis and determining response to
      therapy. Some assessments are similar in both diseases, e.g. measuring joint
      pain, the number of involved joints and functional impairment. There are also
      areas of difference; for example, rheumatoid arthritis is a systemic disease with
      immune disturbance and positive tests for rheumatoid factor and elevated acute
      phase markers while osteoarthritis is a more local disease with little systemic
      upset. In both diseases pain and progressive joint damage result in increasing
      disability. There is agreement on a core data set in rheumatoid arthritis which
      comprises: swollen joint counts, tender joint counts, pain assessment, patient's
      global assessment, an acute phase marker such as the ESR and a self-administered
      functional questionnaire. There is less agreement on the core data set in
      osteoarthritis, though pain and functional impairment are both important.
      Combined or overall indices have been used in both rheumatoid arthritis (e.g. the
      disease activity score) and in osteoarthritis (e.g. the Lequesne functional
      index), but there is no general agreement on their value. In both diseases plain
      radiology is useful to define diagnostic groups and follow progression in long
      term studies. Mortality is increased in rheumatoid arthritis and is useful for
      defining the long term effects of the disease; little is known about mortality in
      osteoarthritis. Standardizing clinical methods is important and much work is
      needed in this area.

PMID- 9010082
TI  - The pathophysiology of cartilage and synovium.
AB  - To interpret joint imaging it is necessary to understand the pathology of the
      joint. It is not possible to describe the pathology of every joint disease, nor
      is it relevant. In this paper the pathophysiology of the major joint changes,
      cartilage loss, change in subarticular bone, increase in joint fluid, and
      thickening of the synovium, that can be visualized by MRI are described and
      discussed.

PMID- 9010083
TI  - Proposed scoring system for assessing synovial membrane abnormalities at
      arthroscopy in knee osteoarthritis.
AB  - The synovial membrane is thought to play an important role in both the clinical
      and the anatomical evolution of osteoarthritis. Arthroscopy performed under local
      anaesthesia on an outpatient basis has been proposed as a means of cartilage and
      synovial assessment for research purposes. The authors propose a scoring system
      for assessing anterior synovial abnormalities at arthroscopy in knee
      osteoarthritis. This synovitis score takes into account the intensity and the
      extent of synovial lesions.

PMID- 9010084
TI  - Microfocal techniques in quantitative radiography: measurement of cancellous bone
      organization.
AB  - Microfocal radiography records, with unusually good resolution, the detailed
      structural organization of cancellous bone. A textural imaging method, fractal
      signature analysis (FSA), was used to quantify the horizontal and vertical
      trabecular organization recorded within macroradiographic images of the spine of
      post-menopausal women and the tibia in osteoarthritic knees, and the analysis of
      variance method was applied to the wrist and hand of rheumatoid patients. Changes
      in trabecular structure were found to correlate with (i) body weight, age and
      bone mineral density in the lumbar spine of post-menopausal women; (ii) the
      degree of cartilage loss and age in the tibia of patients with knee OA; and (iii)
      analysis of variance quantified the extent of 'normal', osteopaenic and eroded
      bone in rheumatoid joints. Quantitation of cancellous bone organization can add
      significantly to our understanding of disease processes and effect of therapy in
      diseased joints.

PMID- 9010085
TI  - Mapping abnormal synovial vascular permeability in temporomandibular joint
      arthritis in the rabbit using MRI.
AB  - An automated method for two-dimensional spatial depiction (mapping) of
      quantitative physiological tissue characteristics derived from contrast-enhanced
      MRI was applied to a model of inflammatory disease represented by antigen-induced
      arthritis of the temporomandibular joint in the rabbit. Specifically, an
      established two-compartment kinetic model of unidirectional mass transport was
      implemented on a pixel-by-pixel basis to generate maps of tissue permeability
      surface area product (PS) and fractional blood volume (BV) based on dynamic MRI
      intensity data after administration of albumin-(Gd-DTPA)30, a prototype
      macromolecular contrast medium designed for blood pool enhancement. Maps of PS
      and BV in a disease model of induced arthritis clearly depicted zones of
      increased permeability (up to approximately 200 microliters/cc/h-compared to 25
      microliters/cc/h in normal tissues).

PMID- 9010086
TI  - Prognostic value of contrast enhanced Gd-DTPA MRI for development of bone erosive
      changes in rheumatoid arthritis.
AB  - Conventional radiograms have been used to quantitate the progression of
      rheumatoid arthritis, mainly through the assessment of bone erosions, but this
      approach has many limitations. It has been suggested that an advantage of
      contrast-enhanced Gd-DTPA MRI over radiography may be its prognostic value due to
      its ability to show the natural history of active destructive to inactive fibrous
      pannus. The aim of this study was to evaluate the possible prognostic value of
      MRI for future development of bone erosive changes in small hand joints in
      patients with RA. The results of the study confirm that in joints in which
      inflammatory active pannus is shown by contrast-enhanced MRI, progression of bone
      destructive changes can be expected.

PMID- 9010087
TI  - Intravenous MRI contrast enhancement of inflammatory synovium: a dose study.
AB  - A dose study was performed of MRI intravenous contrast medium enhancement of
      rheumatoid synovium in the knee, comparing the enhancement with gadoteridol at
      doses of 0.1 and 0.3 mmol/kg. A measurable and significant difference was
      demonstrated which has particular relevance to the accuracy of dose calculations
      needed when performing quantitative studies.

PMID- 9010088
TI  - MRI evaluation of the knee in rheumatoid arthritis.
AB  - The knees of forty-three patients suffering from rheumatoid arthritis (RA) were
      examined using pre- and post-contrast MRI in an attempt to assess the extent and
      frequency of all abnormalities in the RA knee. Features evaluated by MRI were:
      synovial thickening, joint effusion, bone destruction, popliteal cysts,
      periarticular soft tissue swelling, abnormal tendons and bone marrow changes. A
      scoring system (0-2) was used to determine the relationship between the various
      signs of RA in order to identify those that may be relevant for the assessment of
      therapeutic response. It seems that the assessment of inflamed synovium is the
      major criterion for the determination of disease activity in RA.

PMID- 9010089
TI  - MRI in assessment of the systemic manifestations of rheumatological disease.
AB  - Magnetic resonance imaging (MRI) has emerged as complementary imaging modality to
      conventional radiography. The same diagnostic rules that are used in the
      interpretation of the routine radiographs should be applied to the analysis of MR
      images with the macroscopic spread of the disease as a main diagnostic clue. MRI
      has been shown to be a sensitive tool in detecting early arthritic changes and
      erosions, inflammation in periarticular tendons and tendon sheaths, and in
      juxtaarticular bursae. MRI plays a pivotal role in diagnosis of arthritis of the
      craniocervical junction and its complications. It also has been used effectively
      to detect insufficiency fractures and osteonecrosis. MRI may be important in
      diagnosing early arthritis, in specifying the differential diagnosis of rheumatic
      disease, and in selecting subgroups of patients to provide tailored therapeutic
      regimens.

PMID- 9010090
TI  - Contrast-enhanced MRI of rheumatic joint disease.
AB  - Early MR diagnosis of inflammatory rheumatic joint disease relies on the
      detection of the proliferating synovium. Several studies have shown that reliable
      visualization of the inflamed synovium is dependent upon the enhancement provided
      by intravenously injected paramagnetic contrast media. This presentation
      discusses the role of contrast-enhanced MRI in the assessment of inflammatory
      rheumatic joint disease. It is concluded that the method may aid in early
      diagnosis, and that it has a great potential in the assessment of disease
      severity and inflammatory activity.

PMID- 9010091
TI  - Maurice M. Black, M.D. in memoriam.

PMID- 9010092
TI  - Vascular endothelial growth factor expression in primary esophageal squamous cell
      carcinoma. Association with angiogenesis and tumor progression.
AB  - BACKGROUND: Angiogenesis is essential for solid tumor growth and metastasis.
      Vascular endothelial growth factor (VEGF), a recently identified growth factor
      with significant angiogenic properties, may be a major tumor angiogenesis
      regulator in vivo. Conversely, there have been few studies of the association
      between angiogenic factor expression and angiogenesis in esophageal carcinoma.
      The authors examined VEGF expression and microvessel density in esophageal
      squamous cell carcinomas to clarify the association of VEGF expression with the
      clinicopathologic features of the disease. METHODS: Surgical specimens from 75
      primary esophageal squamous cell carcinomas were examined for VEGF expression and
      microvessel density by immunocytochemical staining. Original anti-VEGF polyclonal
      antibody was used to determine VEGF expression, and antifactor VIII antibody was
      used to determine microvessel density. The isoforms of VEGF mRNA were determined
      by reverse transcriptase-polymerase chain reaction. RESULTS: Thirty-five (46.7%)
      of the 75 esophageal carcinomas were positive for VEGF protein. There was a close
      correlation between microvessel density and VEGF positivity (P = 0.0002). High
      VEGF levels were significantly associated with well differentiated tumors,
      advanced stage (depth of invasion and blood vessel invasion), high incidence of
      distant metastases after surgery, and poorer prognosis. CONCLUSIONS: The results
      of this study suggest that VEGF expression is associated with tumor progression
      and poor prognosis by stimulating angiogenesis in esophageal squamous cell
      carcinoma.

PMID- 9010093
TI  - Direct measurement of doxorubicin concentration in the intact, living single
      cancer cell during hyperthermia.
AB  - BACKGROUND: It is well known that the effect of doxorubicin on cancer cells is
      enhanced by hyperthermia. The mechanism of this phenomenon is not fully
      understood. METHODS: Two esophageal squamous cell carcinoma cell lines, TE-2 and
      TE-6, were used; these cell lines have different sensitivities for doxorubicin.
      The cells were exposed to 1 microgram/mL of doxorubicin for 30 minutes. With a
      confocal laser scanning microscope and a transparent warming plate, doxorubicin
      concentration was measured continuously in the intact, living single cancer
      cells, and the two-dimensional distribution of the drug during hyperthermia (43
      degrees C) was analyzed. RESULTS: A doxorubicin sensitivity difference was
      confirmed between TE-2 and TE-6 cells by colonogenic assay (P < 0.05).
      Hyperthermia increased the sensitivity of both cell lines to the drug (P < 0.05)
      and eliminated the sensitivity difference. Doxorubicin accumulated in the nuclei
      in both cell lines 30 minutes after exposure to the drug in a time-dependent
      manner (P < 0.05). Without hyperthermia, the doxorubicin concentration in the
      nuclei of the TE-2 cells (4.8 +/- 0.3 micrograms/mL) was higher than in the
      nuclei of the TE-6 cells (2.3 +/- 0.5 micrograms/mL) (P < 0.05). With
      hyperthermia, there was no significant difference in doxorubicin concentration
      between the nuclei of the TE-2 cells (20.8 +/- 1.3 micrograms/mL) and the nuclei
      of the TE-6 cells (16.5 +/- 3.9 micrograms/mL). CONCLUSIONS: Hyperthermia
      increased the uptake of doxorubicin in the nuclei of cancer cells. Thus, the
      authors concluded that hyperthermia increases the cells' sensitivity to the drug.

PMID- 9010094
TI  - Tumor vascularity correlates with the prognosis of patients with esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Angiogenesis is essential for the growth of solid tumors.
      Intratumoral microvessel count, which represents a measure of tumor angiogenesis,
      has been associated with the overall survival of patients with a variety of
      malignancies. However, little is known about the significance of
      neovascularization in esophageal squamous cell carcinoma. METHODS: In this study,
      the role of tumor angiogenesis as a prognostic indicator was examined in
      esophageal squamous cell carcinomas from 43 patients. Vascular endothelial cells
      were stained with anti-CD34 and anti-von Willebrand factor monoclonal antibodies
      before being quantitated by light microscopy (x 200). RESULTS: Significant
      correlation between vessel counts for two antibodies was observed, although
      counts for CD34 were approximately three times higher. Intratumoral vessel counts
      were significantly higher in tumors with deeper penetration. Multivariate
      analyses indicated that vessel counts determined by either CD34 or von Willebrand
      factor staining, as well as lymph node metastasis, were identified as significant
      and independent prognostic factors in patients with esophageal squamous cell
      carcinoma. CONCLUSIONS: These findings support the hypothesis that tumor
      angiogenesis is closely related to the overall survival of patients with
      esophageal squamous cell carcinoma. The extent of tumor vascularity may serve as
      a reliable prognostic marker with which patients at risk for recurrence can be
      identified.

PMID- 9010095
TI  - Gene amplification and proliferative kinetics in relation to prognosis of
      patients with gastric carcinoma.
AB  - BACKGROUND: The differences in survival of gastric carcinoma patients who have
      identical clinical or pathologic stages prompted the authors to investigate the
      prognostic significance of biologic features that are known to affect the
      clinical aggressiveness of other tumor types. METHODS: One hundred twenty-four
      tumor samples from patients who had received radical or palliative surgery were
      analyzed for c-myc, c-K-ras, hst, and c-erb B-2 gene amplification by means of
      the Southern blot technique. Of these tumors, 70 were also examined for cell
      kinetics by means of the thymidine labeling index (TLI). RESULTS: The analysis of
      associations between gene amplification and the anatomicopathologic variables
      (TNM classification, site of tumor, and histology) showed that amplification
      represents a late event in the natural history of gastric carcinoma. Gene
      amplification showed a slight, statistically insignificant, negative impact on
      overall survival (OS) (P = 0.09). Amplification of c-erb B-2 correlated in a
      statistically significant way with reduced OS (P = 0.03). Cox multiple regression
      analysis revealed that neither c-erb B-2 amplification nor TLI had prognostic
      significance in relation to OS. CONCLUSIONS: These data indicate that
      amplification of the examined oncogenes did not reveal a new independent
      prognostic factor for patients with gastric carcinoma. However, the authors'
      results did show a strong correlation between gene amplification and tumor
      progression, which warrants further study involving larger series of patients. At
      the same time, the TLI results underlined the need to identify the most suitable
      biologic material for use in the estimation of proliferative indexes in gastric
      carcinoma.

PMID- 9010097
TI  - Osteogenic sarcoma of the extremity with detectable lung metastases at
      presentation. Results of treatment of 23 patients with chemotherapy followed by
      simultaneous resection of primary and metastatic lesions.
AB  - BACKGROUND: In the past 20 years, it has been demonstrated that the combination
      of surgery and chemotherapy improves the prognosis for patients with osteosarcoma
      of the extremity without detectable metastases at presentation. By contrast, the
      efficacy of chemotherapy coupled with aggressive surgery has not yet been well
      established for patients with metastatic disease at diagnosis. The current study
      evaluates the efficacy of chemotherapy associated with simultaneous surgery of
      primary and metastatic lesions in patients presenting with osteosarcoma of the
      extremity with lung metastases. METHODS: Patients with lung metastases
      originating from an osteosarcoma of the extremity received chemotherapy (high
      dose methotrexate, cisplatin, doxorubicin, and ifosfamide) followed by
      simultaneous resection of primary and metastatic lesions and additional
      chemotherapy. RESULTS: Between January 1993 and June 1995, 23 patients entered
      the study. After primary chemotherapy, lung metastases disappeared in three
      patients, whereas in four patients they remained surgically unresectable. All
      seven patients received surgical treatment of the primary tumor only. In the
      remaining 16 patients, a simultaneous resection of the primary and metastatic
      tumors was performed after chemotherapy. The resection of metastatic lesions
      resulted in a complete remission in 15 patients and an incomplete remission in 1
      patient. All five patients who never achieved tumor free status died within a few
      months. Of the 18 patients who achieved radiologic remission at a 30-month follow
      up (range, 14-50 months), 10 (55.5%) remained continuously free of disease, 7
      relapsed with new metastases, and 1 died of toxicity. In 13 of the 18 patients
      who underwent a complete simultaneous resection of the primary and the metastatic
      lesions, or whose pulmonary metastases disappeared after chemotherapy, a strong
      correlation was found between degree of necrosis of the primary tumor and of the
      metastatic tumor. CONCLUSIONS: In patients presenting with osteosarcoma of the
      extremity with lung metastases, the combination of aggressive chemotherapy with
      simultaneous resection of the primary and metastatic lesions improves
      traditionally negative outcomes. The strong correlation found between the
      histologic response of the primary and metastatic tumors supports the strategy,
      largely used currently in the neoadjuvant treatment of osteosarcoma, of tailoring
      postoperative chemotherapy on the basis of the histologic response of the primary
      tumor to preoperative chemotherapy.

PMID- 9010096
TI  - The significance of allelic deletions and aneuploidy in colorectal carcinoma.
      Results of a 5-year follow-up study.
AB  - BACKGROUND: A prospective study was initiated to analyze the prognostic value of
      both the deletion of candidate tumor suppressor genes and the DNA content in
      colorectal carcinoma specimens. METHODS: A prospective study was initiated in
      1988, into which 104 patients from the Brooklyn VA Medical Center were accrued
      through March 1992. DNA restriction endonuclease digests, obtained by the
      Southern blot technique, were examined for allelic deletions by cDNA probes pnm23
      H1 (17q21) YNZ 22.1 (17p13), and p15-65 (18q21). DNA content was measured by
      image analysis cytometry of Feulgen-stained tumor imprints. Median follow-up was
      5.5 years (range, 4-8.5 years). RESULTS: Patients with nm23-H1 allelic deletions
      were 3 times as likely to develop distant metastases as patients without nm23-H1
      deletions (relative risk [RR], 3.89; 95% confidence interval [CI], 1.39, 10.89).
      This connection was even stronger after adjustment for TNM stage and site of
      primary tumor (RR, 5.27; 95% CI, 1.67, 16.68). No significant association of 17p
      or 18q deletions or ploidy with either distant metastases or overall survival was
      noted. In multivariate analysis, clinicopathologic variables associated with
      decreased survival included intracellular mucin production, nuclear grade, TNM
      stage, and nerve invasion. CONCLUSIONS: A combination of clinicopathologic and
      molecular biologic variables may identify patients at high risk for death from
      disseminated colorectal carcinoma.

PMID- 9010098
TI  - Prostaglandin levels of primary bone tumor tissues correlate with peritumoral
      edema demonstrated by magnetic resonance imaging.
AB  - BACKGROUND: Several reports have shown peritumoral edema accompanying primary
      bone tumors demonstrated by magnetic resonance imaging (MRI). However, the
      mechanism of this inflammatory reaction is still unclear. The authors postulated
      that the reaction was caused by some chemical mediators including prostanoids,
      because several investigators have observed that some types of bone tumors
      synthesize prostanoids. Therefore, the authors compared MRI findings and tumor
      prostaglandin (PG) levels. METHODS: The subjects were 29 patients with primary
      bone tumor or tumor-like conditions: chondroblastoma (n = 5); chondrosarcoma,
      including rare variants (n = 8); giant cell tumor (n = 6); osteochondroma (n =
      5); osteoblastoma (n = 2); Ewing's sarcoma (n = 2); and eosinophilic granuloma (n
      = 1). T1- and T2-weighted spin echo images were obtained in all but one patient
      before surgery. The tumor concentration of prostaglandin E2, 6-keto-PGF1 alpha,
      and thromboxane B2 were measured by radioimmunoassay. RESULTS: MRI distinctly
      showed bone marrow edema in 9 and soft tissue edema in 12 of the 28 patients
      examined. These findings were significantly correlated with the PG levels.
      Moreover, the PG levels were correlated with the histologic classifications (P <
      0.001). In particular, the chondroblastomas showed prominent concentrations of
      PGs compared with other cartilaginous tumors or giant cell tumors. CONCLUSIONS:
      Although peritumoral edema accompanying benign and malignant bone tumors is not
      necessarily related to one single pathophysiologic mechanism, these results
      suggest that PG production was an important cause of the inflammatory reaction
      that was revealed by MRI. Recognition of this phenomenon is advantageous not only
      for strict diagnostic purposes but also for understanding the characteristic
      features of individual primary bone tumors.

PMID- 9010099
TI  - Behcet's disease associated with myelodysplastic syndromes. A case report and a
      review of the literature.
AB  - BACKGROUND: Behcet's disease has rarely been reported in association with
      myelodysplastic syndromes (MDS). Increased production of reactive oxygen species
      (ROS) by neutrophils has a primary role in the pathogenesis of Behcet's disease.
      However, decreased production of ROS by neutrophils has frequently been reported
      in patients with MDS. The current study was undertaken to determine the role of
      ROS production in a patient with Behcet's disease and MDS. METHODS: A patient
      with MDS with trisomy 8 who developed Behcet's disease is described and a review
      of the literature of patients with Behcet's disease in MDS is presented. The
      production of ROS by neutrophils was investigated by luminol-enhanced
      chemiluminescence (CL) assay. RESULTS: Based on a review of the literature, 10
      cases of Behcet's disease associated with MDS have been reported to date. Nine
      patients had undergone cytogenetic analysis of bone marrow cells, 7 of whom (78%)
      had trisomy 8. Neutrophils taken from the authors' patient during the active
      phase of Behcet's disease demonstrated an increased CL response. Moreover, serum
      from this patient increased the CL emission of neutrophils from healthy
      volunteers. CONCLUSIONS: These data suggest that trisomy 8 predisposes to
      Behcet's disease in patients with MDS. Furthermore, an increased ROS production
      by neutrophils may be associated with the diverse clinical findings in this
      disease. In this study, neutrophils were activated directly by serum factors.

PMID- 9010100
TI  - Anti-HTLV-1 antibody positive cutaneous T-cell lymphoma.
AB  - BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a neoplasm of the mature
      helper T-lymphocyte. Human T-lymphotropic virus type 1 (HTLV-1) has been shown to
      be the cause of this neoplasm. Recently, however, the HTLV-1 genome has been
      found in some patients with cutaneous T-cell lymphoma (CTCL), which suggests a
      causal relation of HTLV-1 to CTCL. Thus, the relation between the HTLV-1 genome
      and CTCL, as well as the difference between ATLL and CTCL, have come into
      question. METHODS: The authors examined two patients with CTCL whose serum anti
      HTLV-1 antibodies were constantly positive. The Southern blot technique, inverse
      polymerase chain reaction (IPCR), and polymerase chain reaction (PCR) with four
      sets of primers for gag, pol, env, and pX regions of HTLV-1 were used to clarify
      the distinctions between ATLL and CTCL. RESULTS: Clinically, one patient
      presented with multiple subcutaneous nodules with involvements of the internal
      organ, and the other patient was typical for mycosis fungoides. No integration of
      HTLV-1 DNA was detected by IPCR or the Southern blot technique in either patient.
      PCRs with the four sets of primers were all found to be positive for HTLV-1
      except one. CONCLUSIONS: The authors conclude that ATLL should be differentiated
      from CTCL in view of the responsibility of HTLV-1 for promoting or maintaining
      CTCL.

PMID- 9010101
TI  - Cutaneous malignant melanoma in southern Sweden 1965, 1975, and 1985. Prognostic
      factors and histologic correlations.
AB  - BACKGROUND: There is a worldwide increase in the incidence of cutaneous malignant
      melanoma (CMM) among whites. In Sweden, a five-fold increase has been recorded
      since 1960, although the increase in mortality rate is substantially lower. Tumor
      thickness is recognized as the most important histologic prognostic factor for
      primary melanoma. In a previous study, the authors did not find any significant
      decrease in mean tumor thickness over the period 1965-1985 in their region. In
      the current study, prognostic factors for melanoma were evaluated for this time
      period. METHODS: In a population-based study, 468 cases of invasive melanoma,
      diagnosed in the years 1965, 1975, and 1985, were histopathologically reexamined.
      The level of invasion, tumor thickness, regressive reaction, ulceration, presence
      of inflammatory cells, presence of benign nevus cells, and site of presentation
      were studied. In 461 of these 468 patients, it was possible to correlate the
      histopathologic factors with survival. RESULTS: In univariate analyses, the
      parameters of presence of ulceration, increasing tumor thickness, male gender,
      nodular type of melanoma, and older age at diagnosis were significantly related
      to a shortened overall survival. In various multivariate models with adjustment
      for age and the factors studied simultaneously, ulceration, increasing tumor
      thickness, and male gender were significantly associated with a poor prognosis.
      Correlations between the factors studied were noted. It was observed that older
      patients tended to have thicker tumors. Thick melanomas correlated to a deeper
      level of invasion (Clark's), nodular growth pattern, ulceration, less
      inflammation, and less regression compared with thin, less invasive melanomas.
      Women had significantly fewer inflammatory cells and fewer signs of regression in
      their tumors compared with men. CONCLUSIONS: In multivariate analyses adjusted
      for age, increasing tumor thickness, older age, ulceration, and male gender were
      significantly associated with a poor prognosis among patients with invasive CMM.
      None of these factors showed a significant change for the years 1965, 1975, and
      1985. Thus, a change in the prognostic factors studied does not explain the
      increased survival of melanoma patients for this time period.

PMID- 9010102
TI  - Interphase cytogenetic analysis of myxoid soft tissue tumors by fluorescence in
      situ hybridization and DNA flow cytometry using paraffin-embedded tissue.
AB  - BACKGROUND: Myxoid liposarcoma is one of the major myxoid malignancies of soft
      tissue and its histologic differentiation from other myxoid tumors is sometimes
      difficult. Recent cytogenetic analysis revealed that a characteristic reciprocal
      chromosomal translocation of t(12;16)(q13;p11) occurs in myxoid liposarcomas. In
      this study, retrospective cytogenetic analysis by means of fluorescence in situ
      hybridization (FISH) and DNA flow cytometry were performed on free nuclei
      isolated from paraffin embedded myxoid liposarcoma cells, and they were compared
      with myxoid malignant fibrous histiocytomas (MFHs), low grade fibromyxoid
      sarcomas, and intramuscular myxomas. METHODS: Nine myxoid liposarcomas, five
      myxoid MFHs, two low grade fibromyxoid sarcomas, and four intramuscular myxomas
      were examined. Chromosomal aberrations in chromosomes 12 and 16 were investigated
      by FISH, using both centromeric DNA probes and whole chromosome painting probes.
      Cellular DNA contents were determined by flow cytometry. RESULTS: All nine myxoid
      liposarcomas were shown to be diploid by DNA flow cytometry and exhibited the
      translocation t(12; 16), as shown by FISH. Four of the five myxoid MFHs exhibited
      aneuploidy, as shown by flow cytometry, and remarkable numeric aberrations of
      chromosomes 12 and 16. No abnormal DNA content or chromosomal aberrations were
      identified in the two low grade fibromyxoid sarcomas or the four intramuscular
      myxomas. CONCLUSIONS: FISH analysis performed on paraffin embedded materials can
      be used to differentiate myxoid liposarcomas from other myxoid soft tissue
      tumors.

PMID- 9010103
TI  - Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases
      suggesting a malignant potential higher than currently recognized.
AB  - BACKGROUND: The goal of this study was to characterize the clinicopathologic
      features of follicular dendritic cell sarcoma, a very uncommon neoplasm. METHODS:
      The 17 cases were collected from the consultation and surgical pathology files of
      the authors, including 8 previously reported cases. The histologic and
      immunohistochemical features and outcome were analyzed. RESULTS: The patients had
      a median age of 40 years, with a slight female predominance. Seven patients
      presented with enlarged lymph nodes, and ten presented with tumor in extranodal
      sites. Two cases were associated with hyaline-vascular Castleman's disease. The
      tumors had an average greatest dimension of 6.7 cm. The most common histologic
      feature was a storiform or fascicular array of spindle, ovoid, or polygonal cells
      with oval nuclei, delicate nuclear membrane, vesicular or granular chromatin,
      distinct nucleoli, indistinct cell borders, and frequently fibrillary cytoplasm.
      There were often scattered multinucleated forms. The tumor cells sometimes formed
      sheets, circular whorls, follicle-like structures, trabeculae, or pseudovascular
      spaces. There was a sprinkling of small lymphocytes, with or without cuffing
      around blood vessels. The neoplastic cells were immunoreactive for CD21 (17 of 17
      cases), CD35 (17 of 17 cases), desmoplakin (10 of 17 cases), epithelial membrane
      antigen (14 of 16 cases), S-100 protein (6 of 17 cases), and CD68 (2 of 17
      cases), but not cytokeratin. Ultrastructural studies showed villous processes
      connected by desmosomes. Only one harbored the Epstein-Barr virus. Among 13
      patients with a median follow-up of 3 years, local recurrence occurred in 6,
      metastasis in 6, and 3 died of disease. CONCLUSIONS: Follicular dendritic cell
      sarcoma exhibits distinctive histologic features that permit its presumptive
      recognition, but a firm diagnosis requires confirmation with special studies.
      Because it has a significant recurrent and metastatic potential (the latter risk
      having been previously underestimated), it should be viewed as an intermediate
      grade malignancy. An intraabdominal location is associated with a particularly
      aggressive clinical course.

PMID- 9010104
TI  - The influence of black race and socioeconomic status on the use of breast
      conserving surgery for Medicare beneficiaries.
AB  - BACKGROUND: This study explores the influence of socioeconomic status (SES) and
      black race on the use of breast-conserving surgery (BCS) as opposed to mastectomy
      for early stage breast carcinoma. METHODS: A cohort of 41,937 female Medicare
      inpatients age 65-79 years who had undergone BCS or mastectomy treatment in 1990
      for local or regional breast carcinoma was studied. SES was estimated based on
      the patients' zip code of residence. RESULTS: Greater use of BCS was associated
      with higher income and increased education as determined by the patients' zip
      code area (P < 0.001 for each), and with lower vacant housing rates and fewer
      persons living below the poverty line in the patients' zip code area (P < 0.001
      for each). Black women were less likely than women of other races to undergo BCS
      (odds ratio, 0.80; 95% confidence interval, 0.71-0.91). However, in a
      multivariate regression model adjusting for stage and urban versus rural
      residence, income, educational status, and poverty rate remained significant
      predictors of patient receipt of BCS, whereas black race did not remain an
      independent predictor of this treatment. CONCLUSIONS: Women residing in higher
      SES areas are more likely to undergo BCS. The reduced use of BCS in black women
      appears attributable to SES.

PMID- 9010105
TI  - Progestin alone as primary treatment of endometrial carcinoma in premenopausal
      women. Report of seven cases and review of the literature.
AB  - BACKGROUND: The standard treatment for endometrial carcinoma is staging
      laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy.
      In an attempt to preserve childbearing potential, selected patients with
      endometrial carcinoma were treated with progestin alone as primary therapy.
      METHODS: Patients were identified through searches of tumor registries and
      solicitation of consulting gynecologic oncologists at the affiliated institutions
      of the University of California-Los Angeles Center for the Health Sciences. Only
      those patients with a diagnosis of endometrial carcinoma treated with progestin
      alone as primary therapy were included in the study. Independent pathologic
      review was performed by a recognized expert gynecologic pathologist to exclude
      cases of endometrial hyperplasia. A MEDLINE search was conducted to identify
      reports of similarly treated patients. RESULTS: Seven patients were treated with
      progestin alone for endometrial carcinoma at the study institution. Fourteen
      additional patients were identified through the literature search. Combining the
      data for all patients, 13 of 21 patients (62%) had an initial response to
      progestins. Three initial responders later developed recurrent disease, one of
      whom was found to have extrauterine disease at laparotomy. Eight of 21 patients
      (38%) did not respond to progestins and underwent more definitive treatment. None
      of these patients later developed recurrent disease. Six viable infants were
      delivered of three patients after therapy. Nineteen of 21 patients were alive
      without evidence of disease at last follow-up. CONCLUSIONS: The results of this
      study show that premenopausal women with endometrial carcinoma may be treated
      successfully with progestin therapy alone as primary therapy to preserve
      childbearing potential.

PMID- 9010106
TI  - Radiotherapy for localized prostate carcinoma. The correlation of pretreatment
      prostate specific antigen and nadir prostate specific antigen with outcome as
      assessed by systematic biopsy and serum prostate specific antigen.
AB  - BACKGROUND: The objective of this study was to correlate the failure pattern of
      localized prostate carcinoma after radiotherapy (RT) with pretreatment (preTx)
      PSA and post-RT nadir PSA, using systematic biopsies and serum PSA in the
      assessment of outcome. METHODS: From January 1990 to February 1994, 207 patients
      treated with external beam RT were followed prospectively with systematic
      transrectal ultrasound-guided biopsies and measurements of serum PSA levels.
      Three hundred forty-three biopsies were performed, with 4-7 samples taken per
      session. The distribution of T classification was as follows: 19 patients had
      T1b, 15 had T1c, 34 had T2a, 79 had T2b/c, 53 had T3, and 7 had T4. Median follow
      up was 36 months (range, 12-70 months). Failures were categorized as biochemical
      (chemF) (PSA > 2.0 ng/mL and > 1 ng/ mL over nadir), local (LF) (positive biopsy
      and PSA > 2), and distant (DF). The Cox proportional hazards model was used for
      multivariate analysis (MVA). RESULTS: Overall, failures were seen in 68 of 207
      patients: 20 LF, 24 DF, 7 LF + DF, and 17 chemF. In univariate analysis, failures
      correlated significantly with preTx PSA, post-RT nadir PSA, T classification, and
      Gleason's score (GS). The total failure rate was 12% for T1b, T1c, and T2a; 39%
      for T2b and T2c; and 60% for T3 and T4 (P < 0.0001). By evaluation with preTx
      PSA, at 36 months the total failure rate was 3% for preTx PSA < or = 5 ng/mL 16%
      for 5.1-10 ng/mL, 32% for 10.1-15 ng/mL, 42% for 15.1-20 ng/mL, 63% for 20.1-50
      ng/mL, and 88% for > 50 ng/mL (P < 0.0001). By evaluation with post-RT nadir PSA,
      at 36 months the total failure rate was 4% for nadir PSA < or = 0.5 ng/ mL, 26%
      for 0.6-1 ng/mL, 33% for 1.1-2 ng/mL, and 92% for > 2 ng/mL (P < 0.0001). In MVA,
      nadir PSA (P < 0.0001) and T classification (P < 0.0005) were independent
      predictors for any failure. LF occurred in 13% of patients (27 of 207). For these
      27 patients, the categorization of T classification was: T1b/T1c/T2a, 7%;
      T2b/T2c, 16%; and T3/T4, 15% (P = not significant). In MVA, only nadir PSA (P =
      0.0004) predicted for LF. DF occurred in 15% of patients (31 of 207). In MVA,
      nadir PSA (P < 0.0001) and T classification (P < 0.0001) predicted for DF, with
      pretreatment PSA of borderline significance (P < 0.05). To assess preTx
      predictors of outcome, post-RT nadir PSA was removed from the model. PreTx PSA
      then became the dominant variable to predict any failure (P < 0.0001), LF (P =
      0.05), chemF (P = 0.0001), and DF (P < 0.003), while T classification also
      predicted for any failure (P = 0.03), chemF (P = 0.05), and DF (P < 0.0001).
      CONCLUSIONS: Systematic prostate biopsies, performed as part of the rigorous
      followup of prostate carcinoma after RT, define the patterns of failure and
      confirm the prognostic value of preTx PSA, post-RT nadir PSA, and T
      classification. Prior to treatment, preTx PSA is the overwhelming independent
      predictor of failure, but it is surpassed by post-RT nadir PSA when this is added
      to the model.

PMID- 9010107
TI  - A multiple prognostic index predictive of disease outcome after irradiation for
      clinically localized prostate carcinoma.
AB  - BACKGROUND: This investigation was conducted to identify independent pretherapy
      disease-related factors associated with disease outcome in patients with
      clinically localized carcinoma of the prostate (CaP) and to develop models that
      incorporated relevant covariates for estimating the risk of disease relapse after
      irradiation (RT). METHODS: The outcome of 500 patients treated only with RT
      between March 1987 and June 1993 for clinical Stages T1-4N0,XM0 CaP was
      evaluated. The risk of disease relapse as a function of individual prognostic
      variables, and combinations thereof, was determined using logistic regression.
      RESULTS: With a median follow-up of 43 months (range, 4-103 months), 69 patients
      (14%) had clinical evidence of local recurrence (27 patients), regional lymph
      node relapse (4 patients), or metastatic relapse (38 patients) within 5 years of
      RT. Forty additional patients (8%) had biochemical relapse based solely on the
      post-RT serum prostate specific antigen (PSA) profile. Clinical tumor stage (P =
      0.0006), Gleason score (P = 0.001) of the diagnostic biopsy specimen, and
      pretherapy PSA (P < 0.0001) were associated with disease relapse. The risk of any
      relapse within 5 years of RT was determined and graphically displayed as risk
      estimate plots for combinations of these pretherapy prognostic variables.
      CONCLUSIONS: The combination of pretherapy clinical tumor (T) stage, Gleason
      score, and PSA level can be used to obtain improved estimates of the risk for
      disease relapse in patients treated solely with RT for clinically localized CaP.
      Risk estimate plots of this type may facilitate exchange of therapeutic outcome
      information, be instrumental in pretherapy decision-making for the new patient
      with this condition, and aid in the selection of patients for future studies.

PMID- 9010108
TI  - Residual pulmonary masses after chemotherapy for metastatic nonseminomatous germ
      cell tumor. Prediction of histology. ReHiT Study Group.
AB  - BACKGROUND: After chemotherapy for a metastatic nonseminomatous germ cell tumor,
      pulmonary masses may be seen on a computed tomography scan. These residual masses
      may contain one of three histologic elements: necrosis, mature teratoma, or
      cancer. Because surgical resection of masses containing only necrosis is
      unnecessary, the authors aimed to predict the histology of these residual masses.
      METHODS: Six study groups contributed patient data on a total of 215 patients
      undergoing thoracotomy after cisplatin-based induction chemotherapy for
      metastatic testicular nonseminomatous germ cell tumors. Logistic regression
      analysis was used to estimate the probability of necrosis, mature teratoma, and
      cancer in relation to predictors known before thoracotomy. RESULTS: The pulmonary
      mass histology was necrosis in 116 patients (54%), mature teratoma in 70 (33%),
      and cancer in 29 (13%). Necrosis was found at thoracotomy in 89% of those
      patients with necrosis at retroperitoneal lymph node dissection (RPLND). Other
      predictors included the primary tumor histology, prechemotherapy tumor marker
      levels, change in mass size during chemotherapy, and the presence of a single,
      unilateral mass. Multivariate combination of predictors yielded reliable models
      (goodness-of-fit tests, P > 0.20), which discriminated necrosis well from other
      histologies, especially if RPLND histology was available (area under the receiver
      operating characteristic curve, 0.86). CONCLUSIONS: This analysis indicated
      subgroups of patients with a high probability of necrosis and a low risk of
      cancer for whom close follow-up of the residual pulmonary mass might be
      considered. In most patients, a RPLND should be performed before a thoracotomy is
      considered, because the probability of necrosis is generally higher at
      thoracotomy than at RPLND and the histology at RPLND is a strong predictor of the
      histology at thoracotomy.

PMID- 9010109
TI  - Small cell neuroendocrine carcinoma of the urinary bladder. A clinicopathologic
      study with emphasis on cytologic features.
AB  - BACKGROUND: Primary small cell neuroendocrine carcinoma (SCNEC) of the urinary
      bladder is a rare but important entity. The authors have attempted to define the
      cytopathologic features of this tumor. METHODS: Sixty-one urine specimens (16
      with histologic correlation) from 23 patients were studied. Twenty patients were
      male and 3 were female with an age range of 43 to 86 years (mean age, 68.8
      years). Twenty-one cases were pure SCNEC and 2 were high grade undifferentiated
      carcinoma with neuroendocrine features. There were no false-positive or false
      negative urine cytology diagnoses, but several cases of SCNEC were originally
      diagnosed as high grade transitional cell carcinoma by cytology. RESULTS:
      Cytologic features of SCNEC included hypercellularity with isolated single cells
      and clustered cells with naked hyperchromatic nuclei, finely granular nuclear
      chromatin, rare nucleoli, and a high mitotic karyorrhectic index. Nuclear molding
      was prominent. No glandular formation or nesting was noted. Half of the cases had
      a bloody, necrotic, or inflamed background. Histology, when available, was
      confirmatory in all cases. CONCLUSIONS: Cytologic features of SCNEC are distinct
      and an accurate urinary cytologic diagnosis can be made. Differential diagnosis
      is limited and includes metastatic small cell carcinoma, high grade transitional
      cell carcinoma, and malignant lymphoma.

PMID- 9010110
TI  - Telomerase activity in bladder carcinoma and its implication for noninvasive
      diagnosis by detection of exfoliated cancer cells in urine.
AB  - BACKGROUND: Telomerase is an enzyme that can reconstitute the ends (telomeres) of
      chromosomes after cell division and thus circumvent the cumulative damage that
      occurs in normal adult somatic cells during successive mitotic cycles. Recently,
      it has been proposed that this enzyme should, therefore, be detectable in
      immortal malignant cells but not in their normal counterparts, which stop
      dividing and senesce. Accordingly, telomerase activity has been reported in many
      types of malignant tumors, including those of the gastrointestinal tract, breast,
      and lung but little information was available regarding its status in bladder
      carcinoma or in exfoliated cancer cells. METHODS: In the current study,
      telomerase activity was examined by a polymerase chain reaction-based assay
      designated TRAP (telomeric repeat amplification protocol) in tissue samples from
      56 bladder carcinomas, 17 nonneoplastic bladder lesions, and 2 dysplastic lesions
      of the urinary tract. The feasibility of identifying cancer patients by the
      detection of telomerase activity in exfoliated cancer cells in the urine was also
      investigated. Such activity was assayed in centrifuged urine cell pellets from 26
      bladder carcinoma patients and from 83 patients with no evidence of malignant
      disease. RESULTS: Evidence of telomerase was detected in solid tissue specimens
      from 48 of the 56 bladder carcinomas (86%) regardless of tumor stage or
      differentiation, whereas it was not found in any normal bladder tissue specimen.
      However, it was present in the dysplastic bladder lesions as well as in nearly
      all Stage I well differentiated carcinomas, suggesting that its activation occurs
      for the early stages of carcinogenesis and could perhaps be a useful marker for
      the detection of early primary or recurrent bladder tumors. Telomerase activity
      was detected with various signal intensities in urine specimens from 16 of the 26
      patients with bladder carcinoma (62% sensitivity), whereas only 3 of 83
      nonmalignant urine samples showed any activity (96.4% specificity); this was very
      weak. CONCLUSIONS: These results suggest that telomerase could be a good
      diagnostic marker for the early noninvasive identification of patients with
      bladder carcinoma by facilitating the detection of exfoliated immortal cancer
      cells in their urine.

PMID- 9010111
TI  - Supratentorial World Health Organization Grade 2 astrocytomas and
      oligoastrocytomas. A new pattern of prognostic factors.
AB  - BACKGROUND: Prognostic factors for adult patients with supratentorial World
      Health Organization (WHO) Grade 2 astrocytomas and poorly defined. METHODS: The
      prognostic importance of pretreatment patient- and tumor-related factors was
      analyzed retrospectively in 197 adult patients with supratentorial astrocytomas
      (n = 153) or oligoastrocytomas (n = 44) using the multivariate Cox proportional
      hazards model. Endpoints were death and date of malignant transformation. All
      patients were treated similarly between 1979 and 1992 with iodine-125 implants as
      the primary treatment. RESULTS: A new prognostic pattern was detected.
      Unfavorable prognostic factors with regard to survival were 1) a tumor volume >
      or = 20 mL; 2) a performance status < or = 80; and 3) age > or = 40 years for the
      female subpopulation. Midline shift (another important tumor-related factor after
      univariate analysis) was highly correlated with tumor volume and therefore not
      included in the multivariate model. Risk factors of malignant transformation were
      1) a tumor volume > or = 20 mL; 2) an enhancement in the computed tomography
      scan; and 3) age > or = 40 years for the female subpopulation. Prognostic factors
      created subsets of patients with 5-year survival rates ranging from as low as 5%
      to as high as 79%. CONCLUSIONS: Any treatment decision or evaluation of treatment
      efficacy should take into account the strong influence of both patient- and tumor
      related factors. Any further study design should consider the detected
      interaction between gender and age and the importance of tumor volume.

PMID- 9010112
TI  - Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and
      the prognostic value of chromosomal abnormalities and cyclin D1 overexpression.
AB  - BACKGROUND: Abnormalities of chromosome band 11q13 are frequent in squamous cell
      carcinoma of the head and neck (SCCHN). The oncogene CCND1 is located at 11q13
      and encodes cyclin D1, a cell cycle-regulating protein. The authors investigated
      the clinical relevance and associations between amplification and overexpression
      of cyclin D1 and 11q13 rearrangements. METHODS: The study involved two series of
      patients. In Series 1, overexpression of cyclin D1 and 11q13 rearrangements,
      assessed by immunohistochemistry and cytogenetics, respectively, were compared
      with clinical data in 75 patients with SCCHN. Patients were monitored for at
      least 18 months or until death. In another 23 patients (Series 2), the authors
      investigated the association between DNA amplification (by slot blot
      hybridization), overexpression of cyclin D1, and cytogenetics. RESULTS: In Series
      1, 9 of 75 tumors (12%) had 11q13 aberrations, 6 of which manifested elevated
      expression of cyclin D1. Patients with tumors strongly positive for cyclin D1 (n
      = 9) and those with tumors showing 11q13 rearrangements had poorer survival (P =
      0.047 and 0.005, respectively). However, the correlation between these two
      variables was weak (P = 0.12). In Series 2, 17 of 23 tumors (74%) showed elevated
      cyclin D1 protein expression, and 6 of these showed gene amplification as well.
      Of these six, only one revealed 11q13 rearrangements. CONCLUSIONS: Overexpression
      of cyclin D1 and 11q13 rearrangements are independent prognostic factors for
      SCCHN. In general, DNA amplification results in overexpression of cyclin D1, but
      additional genetic mechanisms are involved in the deregulation. Furthermore,
      oncogenes at 11q13 besides CCND1 may be involved in the tumorigenesis.

PMID- 9010113
TI  - Gastric lymphomas compared with lymph node lymphomas in a population-based
      registry differ in stage distribution and dissemination patterns but not in
      patient survival.
AB  - BACKGROUND: Non-Hodgkin's lymphoma (NHL) originating in mucosa-associated
      lymphoid tissue (MALT) is supposed to have different clinical behavior from lymph
      node NHL. To test this hypothesis, the authors compared data of gastric NHL
      patients with lymph node NHL patients in a population-based registry for
      differences in clinical presentation and prognosis. METHODS: Data from 1981-1989
      on patients with primary gastric NHL (n = 109) and patients with primary lymph
      node NHL (n = 658) were retrieved from a Dutch population-based NHL registry.
      Patients were compared for stage distribution, involved sites, and survival. The
      prognostic value of grading lymphomas according to the malignancy grades of the
      Working Formulation for Clinical Usage was compared with the value of grading
      MALT NHLs as either low grade or high grade malignancies. RESULTS: Patients with
      gastric NHL presented more often with localized disease. Stage IV patients had a
      higher rate of dissemination to other non-lymph node sites but less frequent
      localization in the bone marrow. The restricted pattern of dissemination was
      reflected in a significantly lower recurrence rate for gastric NHL. Gastric NHL
      patients had significantly better disease free survival than lymph node NHL
      patients (80% and 44% at 5 years, respectively; P < 0.001). In contrast, overall
      survival did not significantly differ between the two groups, and it appeared to
      depend on disease stage. Grading MALT lymphoma as either low grade (26%) or high
      grade (70%) malignancies did not provide better prognostic information than
      grading according to the Working Formulation for Clinical Usage (low 8%,
      intermediate 75%, high 9%). CONCLUSIONS: Primary gastric NHL shows a restricted
      dissemination pattern, which gives support to the MALT lymphoma concept. Although
      this might explain the superior disease free survival observed for gastric NHL
      patients, it does not translate into better overall survival for these patients.

PMID- 9010114
TI  - Pigmented extraadrenal paragangliomas. A clinicopathologic and
      immunohistochemical study of five cases.
AB  - BACKGROUND: Pigmented extraadrenal paragangliomas are unusual neoplasms that have
      rarely been reported in the literature. METHODS: The clinical, pathologic, and
      immunohistochemical features of five cases of pigmented extraadrenal
      paragangliomas were reviewed. RESULTS: The patients were 2 women and 3 men within
      the ages of 17 and 56 years (mean age: 36.5). Two neoplasms were located in the
      lumbar spine, one in the urinary bladder, one in the anterior mediastinum, and
      one in the retroperitoneum. Clinically, one patient with spinal paraganglioma
      presented with symptoms of numbness and weakness of the lower extremities whereas
      the second patient had low back pain of several weeks' duration. The
      paraganglioma of the bladder occurred in a pregnant woman who had symptoms of
      dysuria and microscopic hematuria whereas the patient with an anterior
      mediastinal tumor presented with chest pain. No clinical history was obtained
      from the patient with the retroperitoneal tumor. None of the patients had a
      history of hypertension. Grossly, the tumors were described as well
      circumscribed, soft, and slightly hemorrhagic, and measured from 2 to 9 cm in
      greatest dimension. Histologically, the five tumors displayed characteristics
      similar to those described in these tumors, mainly the presence of an organoid or
      zellballen growth pattern. In addition, they contained moderate amounts of
      intracellular melanin pigment that focally obscured the true nature of the
      lesion. Immunohistochemically, four cases were positive for chromogranin whereas
      S-100 protein was detected in the sustentacular cells in four cases. Follow-up
      information ranging from 6 months to 18 years for 3 patients revealed that the
      patients were alive and well without recurrence or metastasis. One patient with
      spinal paraganglioma was lost to follow-up, and the patient with mediastinal
      paraganglioma was a recent case and therefore the behavior of the paraganglioma
      could not be assessed. CONCLUSIONS: The current study expands the morphologic
      spectrum of extraadrenal paragangliomas and emphasizes the need to consider these
      tumors in the differential diagnosis of pigmented neoplasms. These findings
      suggest that the presence of melanin pigment does not alter the behavior of these
      neoplasms.

PMID- 9010115
TI  - Brain metastases in children with solid tumors.
AB  - BACKGROUND: Brain metastases are uncommon among children with solid tumors.
      However, improvements in survival have increased the period of time during which
      children are at risk for developing these metastases. The authors reviewed brain
      metastases in children with solid tumors treated at the Centre Leon Berard during
      the 9 years between 1987 and 1995. METHODS: Among 486 patients with solid tumors,
      162 eventually developed distant metastases in their disease process, including
      12 brain metastases detected by imaging. The tumor type, clinical setting,
      imaging characteristics, treatment modalities, and outcome were assessed for each
      patient. RESULTS: The most common tumors causing brain metastases were Ewing's
      sarcoma (in three patients), neuroblastoma (in three patients), and osteogenic
      sarcoma (in three patients). At the time of initial diagnosis, 9 of the 12
      patients had metastatic disease. All but one patient initially received intensive
      multiagent chemotherapy, including high dose chemotherapy with bone marrow rescue
      in six patients. The median time from initial diagnosis to the detection of brain
      metastases was 15 months. These metastases were clinically detectable in 10
      patients and subclinical in 2 patients. Brain metastases were present at the time
      of first relapse in five patients. In two patients, the brain was the only site
      of relapse. All other patients had extensive systemic disease. Seven patients had
      multiple brain metastases. Two children underwent surgical resection of solitary
      metastases, and eight were irradiated. One child achieved complete remission
      following chemotherapy and irradiation. All other children died, mostly of their
      systemic disease, within a median period of 3 months. CONCLUSIONS: The
      introduction of effective systemic chemotherapy has changed the patterns of brain
      metastases in children. The increasing incidence of these metastases in patients
      with sarcoma and neuroblastoma suggests that the brain is a pharmacologically
      protected site in patients initially diagnosed with metastatic disease.

PMID- 9010116
TI  - Neoadjuvant chemotherapy for pediatric osteosarcoma patients.
AB  - BACKGROUND: Since the first trial for chemotherapy in children with osteosarcoma
      in 1977, the survival rate has gradually improved. Currently, more than 60% of
      all patients are cured, mainly because of the introduction of intensive
      chemotherapy using doxorubicin, high dose methotrexate, and cisplatin. The
      increased survival rates have promoted efforts to improve the quality of survival
      through the use of limb salvage surgery rather than amputation. Improvements in
      chemotherapeutic efficacy should result in a more favorable outcome and better
      function of the affected limb. The current study evaluated factors that influence
      chemotherapy so that a higher survival rate could be obtained. METHODS: Three
      chemotherapy regimens comprised of doxorubicin, high dose methotrexate,
      cisplatin, and ifosfamide were retrospectively analyzed in 67 pediatric
      osteosarcoma patients. Twenty-three patients were treated with chemotherapy
      comprised of high dose methotrexate and doxorubicin (OOS-A regimen), 25 were
      treated with OOS-A with the addition of cisplatin (OOS-B), and 19 were treated
      with OOS-B with the addition of ifosfamide (OOS-C). RESULTS: The OOS-A regimen
      was poorest in terms of survival (40.6%) compared with the OOS-B (67.5%) and OOS
      C regimens (72.5%) (P < 0.001). There was no significant difference in survival
      between the OOS-B and OOS-C regimens. In the OOS-B regimen, patients who received
      a higher relative dose intensity showed a better prognosis. CONCLUSIONS: These
      findings show that doxorubicin, high dose methotrexate, and cisplatin are the
      most potent drugs and suggest that it is more important to maintain the dose
      intensity of the regimen to improve survival rather than add a new drug.

PMID- 9010117
TI  - Multigene effects influencing each other. International Union Against Cancer
      Study Group on Basic and Clinical Cancer Research.

PMID- 9010118
TI  - A profile of medically serious suicide attempts.
AB  - BACKGROUND: This study identified factors associated with medically serious
      suicide attempts (requiring medical hospitalization). METHOD: Demographic
      information, current psychiatric mental state, suicide attempt and psychiatric
      history characteristics, and DSM-IV diagnoses were compared between 65 patients
      hospitalized for a medically serious suicide attempt (MSSA) and 32 patients seen
      in the emergency room for suicide attempt but not medically hospitalized (NMSSA).
      RESULTS: Those with MSSAs had a higher rate of substance-induced mood disorder
      (but not substance abuse or dependence), while those with NMSSA had more
      attempts, more years since first attempt, and a higher rate of sexual and
      physical abuse, traumatic life events, borderline personality disorder, and
      bipolar disorder. CONCLUSION: Substance-induced mood disorder is an important
      diagnosis in the evaluation of suicidal patients. The vulnerability of mood
      effects caused by substance abuse may lead to a more serious suicide attempt
      despite less extensive psychiatric problems. The most important early psychiatric
      intervention may be the immediate recognition and aggressive treatment of an
      individual's affective and substance use disorders.

PMID- 9010119
TI  - Patients excluded from an antidepressant efficacy trial.
AB  - BACKGROUND: The impact of exclusion criteria on antidepressant trials is rarely
      investigated and poorly understood. We describe specific reasons for exclusion
      from a double-blind comparative trial and analyze the selection procedure and its
      impact on treatment outcome. METHOD: A 6-week randomized double-blind trial for
      depressive disorders recruited patients through outpatient psychiatric services,
      private offices, and health care centers. Of the 612 consecutive patients
      interviewed for a diagnosis according to DSM-III-R, 209 (34%) finally entered the
      trial. RESULTS: 86% of the included patients had no comorbid psychiatric
      disorder, whereas a third of those excluded had at least one (p < .00001).
      Patients were excluded for having chronic alcohol or drug misuse (17%), receiving
      antidepressant drugs (15%), or having physical problems precluding their ability
      to take either of the drugs studied (14%). Some patients could not be included
      because of a referral to other modes of treatment (19%) or organizational
      difficulties (16%). The excluded patients less often suffered from major
      depressive disorder than those who were included in the trial. In particular,
      patients excluded because of suicidal thoughts or intent more often had a history
      of previous major depressive episodes (p = .006) compared with the included
      patients. The most important sociodemographic factors related to exclusion from
      the trial were male sex and unmarried status. CONCLUSION: Patients with previous
      depressive episodes or comorbid disorders were more likely to be excluded from
      the antidepressant efficacy trial. Data on the efficacy of antidepressant drugs
      on this patient population are still only infrequently obtained.

PMID- 9010120
TI  - Comorbidity of posttraumatic stress disorder and irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic disorder that has been
      found to be associated with psychiatric disorders and a history of physical
      and/or sexual abuse. To date, the relationship of posttraumatic stress disorder
      (PTSD) and IBS has not been investigated. The primary purpose of this study was
      to examine the relationship of IBS and PTSD. METHOD: Fifty consecutive IBS
      patients admitted to a clinical treatment study were assessed for IBS, trauma
      history, and psychiatric disorders. RESULTS: Twenty-seven IBS patients (54%) met
      criteria for a psychiatric diagnosis at some time in their lives. Twenty-two
      patients (44%) reported a trauma history. Eighteen (36%) were diagnosed with
      PTSD. Those IBS patients with a trauma history were more likely to have other
      comorbid psychiatric diagnoses. CONCLUSION: These results suggest that IBS is
      often associated with psychiatric disorders, indicating that assessment and
      treatment of these comorbid conditions may be important in the treatment of IBS.
      PTSD, which had not been previously investigated in relation to IBS, had a high
      prevalence, indicating the need for careful trauma and PTSD assessment in
      patients with IBS. Patients with IBS who have a trauma history may be more at
      risk for other comorbid psychiatric disorders than IBS patients without a trauma
      history.

PMID- 9010121
TI  - Predictive value of eosinophilia for neutropenia during clozapine treatment.
AB  - BACKGROUND: Myelotoxicity continues to hinder the widespread use of clozapine in
      the United States. It has been theorized that eosinophilia predicts later
      agranulocytosis and that agranulocytosis occurs due to an immunologic mechanism.
      Our study compares the rates of these dyscrasias in clozapine-treated patients
      and a control group. METHOD: Forty-one patients taking clozapine and 29 patients
      taking haloperidol were monitored for a period of 6 months. Rates of eosinophilia
      and neutropenia were compared between the two treatment groups. RESULTS:
      Treatment-emergent eosinophilia occurred frequently in both haloperidol- and
      clozapine-treated patients. No significant difference was seen between groups in
      the incidence of eosinophilia and neutropenia. CONCLUSION: We find no statistical
      difference between the rates of eosinophilia or neutropenia in haloperidol- and
      clozapine-treated patients. This study does not support the use of eosinophilia
      as a reliable predictor of neutropenia.

PMID- 9010122
TI  - Antidepressant pharmacotherapy and the treatment of depression in patients with
      severe traumatic brain injury: a controlled, prospective study.
AB  - BACKGROUND: Untreated or poorly treated depression in patients who suffer from
      traumatic brain injury can result in greater functional disability and prolonged
      or ineffective hospital and rehabilitation stays. Literature available on the
      pharmacologic treatment of depression after traumatic brain injury is scarce.
      This study investigated in a controlled and prospective manner the use of
      desipramine, a tricyclic antidepressant, in a series of patients with severe
      traumatic brain injury. METHOD: Ten patients with severe traumatic brain injury
      and long-standing depression, as diagnosed by DSM-III-R criteria, were admitted
      to the study because of the intention to be treated with antidepressants. They
      were randomly assigned to blindly start on either desipramine treatment (N = 6)
      or placebo lead-in (N = 4). Patients starting with desipramine stayed on that
      drug; patients starting with placebo lead-in were blindly crossed over to
      desipramine after 1 month if there was no significant improvement demonstrated by
      DSM-III-R criteria. All rating clinicians, physicians, and patients were blind to
      actual treatment and any ratings data. DSM-III-R evaluations were done monthly.
      An affect/mood scale was done every 2 weeks. RESULTS: Of all patients evaluable
      using the DSM-III-R, 6 (86%) of 7 demonstrated resolution of depression and
      depressed mood during desipramine treatment. (Three received desipramine
      throughout the study; 3 others started taking placebo and crossed over to
      desipramine,) One patient refused evaluation on DSM-III-R throughout; 2 patients,
      both on desipramine, dropped out because of adverse effects (seizure, mania). In
      addition, there was statistically significant (p = .001) improvement over time
      and different rates of improvement over time in the treated and untreated groups
      for the affect/mood scale data. CONCLUSION: Results from this small study,
      utilizing a blinded, placebo lead-in design appear to (1) demonstrate the
      clinically significant effectiveness of desipramine in treating long-standing
      depression in a series of patients with severe traumatic brain injury, as rated
      with DSM-III-R criteria; (2) show statistically significant improvement on the
      affect/mood scale data, favoring the treated versus untreated (placebo lead-in)
      group.

PMID- 9010123
TI  - Functional status in depressed patients: the relationship to disease severity and
      disease resolution.
AB  - BACKGROUND: We set out to measure the impact of depression and its clinical
      resolution on patients' functional status. METHOD: The Work and Social Disability
      Scale (WSDS), a five-category investigator-rated scale measuring patient
      functional status, was completed at baseline and study discontinuation in a 56
      day, open, uncontrolled study evaluating the safety of a sustained release (SR)
      formulation of bupropion in 3167 patients at 105 sites. To be included in the
      study, patients had to be 18 years or older, have a diagnosis of depression, and
      be considered appropriate for treatment with bupropion SR. The proportion of
      patients in each WSDS category, for those patients taking more than 7 days of
      bupropion SR (N = 2915), was assessed at screen and study discontinuation. The
      percentage of patients with improved WSDS scores at 56 days was also measured for
      all patients and correlated with patient and treatment characteristics. RESULTS:
      Of the patients entering the trial, 61.8% were markedly or severely impaired in
      their work or social activities, and only 5.4% were mildly or not impaired. At
      study discontinuation, more than 54% of patients were judged by the investigator
      to have very much or much improvement in their clinical symptoms. Results on the
      WSDS correlated with the clinical improvements; only 22.3% were markedly or
      severely impaired; and 50.0% were mildly or not impaired at study
      discontinuation. In addition, 63.9% of patients had less work or social
      disability at the end of the trial than at study entry. Functional status
      improved more in patients who had not previously been treated for the episode,
      had more severe depression at study entry, and had a higher dose and duration of
      treatment with bupropion SR. CONCLUSION: The results show that depression results
      in significant impairment in patients' functional status. Functional status
      improved in patients treated with bupropion SR for up to 56 days. This
      improvement was highly correlated with improvement in clinical symptoms and was
      related to patient characteristics at study entry as well as to treatment
      patterns during the study.

PMID- 9010124
TI  - Inability to cry during SRI treatment.

PMID- 9010125
TI  - Fluoxetine-induced akathisia does not reappear after switch to paroxetine.

PMID- 9010126
TI  - Response to risperidone addition in fluvoxamine-refractory obsessive-compulsive
      disorder: three cases.

PMID- 9010127
TI  - Nefazodone and symptoms suggesting neurotoxicity: a case report.

PMID- 9010129
TI  - Mandibular dystonia associated with the combination of sertraline and
      metoclopramide.

PMID- 9010128
TI  - EPS with fever versus NMS.

PMID- 9010130
TI  - Exercise-induced orgasms associated with fluoxetine treatment of depression.

PMID- 9010131
TI  - On the crucial stages in the origin of animate matter.
AB  - Theories of the origin of life have proposed hypotheses to link inanimate to
      animate matter. The theory proposed here derived the crucial stages in the origin
      of animate matter directly from the basic properties of inanimate matter. It
      asked what were the general characteristics of the link, rather than what might
      have been its chemical details. Life and its origin are shown to be one
      continuous physicochemical process of replication, random variation, and natural
      selection. Since life exists here and now, animate properties must have been
      initiated in the past somewhere. According to the theory, life originated from an
      as yet unknown elementary autocatalyst which occurred spontaneously, then
      replicated autocatalytically. As it multiplied to macroscopic abundance, its
      replicas gradually exhausted their reactants. Random chemical drift initiated
      diversity among autocatalysts. Diversity led to competition. Competition and
      depletion of reactants slowed down the rates of net replication of the
      autocatalysts. Some reached negative rates and became extinct, while those which
      stayed positive "survived." Thus chemical natural selection appeared, the first
      step in the transition from inanimate to animate matter. It initiated the first
      animate property, fitness, i.e., the capacity to adapt to the environment and to
      survive. As the environment was depleted of reactants, it was enriched with
      sequels-namely, with decomposition products and all other products which
      accompany autocatalysis. The changing environment exerted a selective pressure on
      autocatalysts to replace dwindling reactants by accumulating sequels. Sequels
      that were incorporated into the autocatalytic process became internal components
      of complex autocatalytic systems. Primitive forms of metabolism and organization
      were thus initiated. They evolved further by the same mechanism to ever higher
      levels of complexity, such as homochirality (handedness) and membranal enclosure.
      Subsequent evolution by the same mechanism generated cellular metabolism, cell
      division, information carriers, and a genetic code. Theories of self-organization
      without natural selection are refuted.

PMID- 9010132
TI  - Erratic evolution of glycerol-3-phosphate dehydrogenase in Drosophila, Chymomyza,
      and Ceratitis.
AB  - We have studied the evolution of Gpdh in 18 fruitfly species by sequencing 1,077
      nucleotides per species on average. The region sequenced includes four exons
      coding for 277 amino acids and three variable-length introns. Phylogenies derived
      by a variety of methods confirm that the nominal genus Zaprionus belongs within
      the genus Drosophila, whereas Scaptodrosophila and Chymomyza are outside. The
      rate of GPDH evolution is erratic. The rate of amino acid replacements in a
      lineage appears to be 1.0 x 10(-10)/site/year when Drosophila species are
      considered (diverged up to 55 million years ago), but becomes 2.3 x 10(-10) when
      they are compared to Chymomyza species (divergence around 60 My ago), and 4.6 x
      10(-10) when species of those two genera are compared with the medfly Ceratitis
      capitata (divergence around 100 My ago). In order to account for these
      observations, the rate of amino acid replacement must have been 15 or more times
      greater in some lineages and at some times than in others. At the nucleotide
      level, however, Gpdh evolves in a fairly clockwise fashion.

PMID- 9010133
TI  - Selection and methionine accumulation in the fat body protein 2 gene (FBP2), a
      duplicate of the Drosophila alcohol dehydrogenase (ADH) gene.
AB  - The Drosophila fat body protein 2 gene (Fbp2) is an ancient duplication of the
      alcohol dehydrogenase gene (Adh) which encodes a protein that differs
      substantially from ADH in its methionine content. In D. melanogaster, there is
      one methionine in ADH, while there are 51 (20% of all amino acids) in FBP2.
      Methionine is involved in 46% of amino acid replacements when Fbp2 DNA sequences
      are compared between D. melanogaster and D. pseudoobscura. Methionine
      accumulation does not affect conserved residues of the ADH-ADHr-FBP2 multigene
      family. The multigene family has evolved by replacement of mildly hydrophobic
      amino acids by methionine with no apparent reversion. Its short-term evolution
      was compared between two Drosophila species, while its long-term evolution was
      compared between two genera belonging respectively to acalyptrate and calyptrate
      Diptera, Drosophila and Sarcophaga. The pattern of nucleotide substitution was
      consistent with an independent accumulation of methionines at the Fbp2 locus in
      each lineage. Under a steady-state model, the rate of methionine accumulation was
      constant in the lineage leading to Drosophila, and was twice as fast as that in
      the calyptrate lineage. Substitution rates were consistent with a slight positive
      selective advantage for each methionine change in about one-half of amino acid
      sites in Drosophila. This shows that selection can potentially account for a
      large proportion of amino acid replacements in the molecular evolution of
      proteins.

PMID- 9010134
TI  - The reverse-transcriptase-like proteins encoded by group II introns in the
      mitochondrial genome of the brown alga Pylaiella littoralis belong to two
      different lineages which apparently coevolved with the group II ribosyme
      lineages.
AB  - The mitochondrial genome of the brown alga Pylaiella littoralis contains two
      different types of group II introns. They each encode complete complex proteins,
      i.e., with a reverse transcriptase domain, a maturase or X domain, and an
      endonuclease or H-N-H/zinc finger domain. To our knowledge, this is the first
      example of the presence in the same genome of introns belonging to subgroups IIA
      and IIB which both contain multidomained RT-like proteins. We describe the group
      IIA introns that interrupt the cox1 gene. The RT-like proteins contained in these
      introns were compared to those of the LSU rDNA group IIB introns. The
      phylogenetic relationships of these intron ORFs were investigated and the
      possible evolution of group II introns is discussed.

PMID- 9010135
TI  - Of worms and men: an evolutionary perspective on the fibroblast growth factor
      (FGF) and FGF receptor families.
AB  - FGFs (fibroblast growth factors) play major roles in a number of developmental
      processes. Recent studies of several human disorders, and concurrent analysis of
      gene knock-out and properties of the corresponding recombinant proteins have
      shown that FGFs and their receptors are prominently involved in the development
      of the skeletal system in mammals. We have compared the sequences of the nine
      known mammalian FGFs, FGFs from other vertebrates, and three additional sequences
      that we extracted from existing databases: two human FGF sequences that we
      tentatively designated FGF10 and FGF11, and an FGF sequence from Caenorhabditis
      elegans. Similarly, we have compared the sequences of the four FGF receptor
      paralogs found in chordates with four non-chordate FGF receptors, including one
      recently identified in C. elegans. The comparison of FGF and FGF receptor
      sequences in vertebrates and nonvertebrates shows that the FGF and FGF receptor
      families have evolved through phases of gene duplications, one of which may have
      coincided with the emergence of vertebrates, in relation with their new system of
      body scaffold.

PMID- 9010136
TI  - Molecular diversity and evolution of blaTEM genes encoding beta-lactamases
      resistant to clavulanic acid in clinical E. coli.
AB  - The molecular diversity of inhibitor-resistant TEM (IRT) enzymes was explored
      using a strategy which involved DNA amplification by polymerase chain reaction
      (PCR), analysis of restriction fragment length polymorphism (RFLP), and direct
      nucleotide sequencing. The study of plasmid-borne genes from 27 strains,
      resistant to amoxicillin and beta-lactamase-inhibitor combinations, identified
      mutations resulting in amino acid change at positions 69, 244, 275, and 276 known
      to be associated with the IRT phenotype and a mutation at nucleotide position 162
      in the promoter region. These mutations were found to lie on two different gene
      sequences, described here as "TEM-1B like" and "TEM-2 like" restriction linkage
      groups. Further analysis, of nucleotide sequences of promoter and coding regions
      of the beta-lactamases, confirmed that a given mutation causing IRT phenotype
      could be associated with two different gene sequence frameworks and two different
      causal mutations could lie on identical gene sequence framework. These data argue
      in favor of convergent phenotypic evolution of IRT enzymes under the selective
      pressure imposed by the intensive clinical use of beta-lactam-beta-lactamase
      inhibitor combinations.

PMID- 9010137
TI  - Conserved clusters of functionally related genes in two bacterial genomes.
AB  - An approach for genome comparison, combining function classification of gene
      products and sequence comparison, is presented. The genomes of Haemophilus
      influenzae and Escherichia coli are analyzed, and all genes are classified into
      nine major functional classes, corresponding to important cellular processes. To
      study gene order relationships and genome organization in the two bacteria, we
      performed statistics on neighboring pairs of genes. To estimate the significance
      of the observations, a statistical model based on binomial distributions has been
      developed. Significant patterns of gene order are observed within, as well as
      between, the two bacterial genomes: Functionally related genes tend to be
      neighbors more often than do unrelated genes. Some of these groups represent well
      known operons, but additional gene clusters are identified. These clusters
      correspond to genomic elements that have been conserved during bacterial
      evolution. In addition to nearest-neighbor relationships, the method is also
      useful to study the relative direction of transcription in genomes, which is also
      highly conserved between homologous gene pairs. This new approach combines the
      high-level description of molecular function with pair statistics that express
      genome organization. It is expected to complement traditional methods of sequence
      analysis in the study of genomic structure, function, and evolution.

PMID- 9010139
TI  - Contribution of mutation and RNA recombination to the evolution of a plant
      pathogenic RNA.
AB  - The nucleotide sequence of 17 variants of the satellite RNA of cucumber mosaic
      virus (CMV-satRNA) isolated from field-infected tomato plants in the springs of
      1989, 1990, and 1991 was determined. The sequence of each of the 17 satRNAs was
      unique and was between 334 and 340 nucleotides in length; 57 positions were
      polymorphic. There was much genetic divergence, ranging from 0.006 to 0.141
      nucleotide substitutions per site for pairwise comparisons, and averaging 0.074
      for any pair. When the polymorphic positions were analyzed relative to a
      secondary structure model proposed for CMV-satRNAs, it was found that there were
      significantly different numbers of changes in base-paired and non-base-paired
      positions, and that mutations that did not disrupt base pairing were preferred at
      the putatively paired sites. This supports the concept that the need to maintain
      a functional structure may limit genetic divergence of CMV-satRNA. Phylogenetic
      analyses showed that the 17 CMV-satRNA variants clustered into two subgroups, I
      and II, and evolutionary lines proceeding by the sequential accumulation of
      mutations were apparent. Three satRNA variants were outliers for these two
      phylogenetic groups. They were shown to be recombinants of subgroup I and II
      satRNAs by calculating phylogenies for different molecular regions and by using
      Sawyer's test for gene conversion. At least two recombination events were
      required to produce these three recombinant satRNAs. Thus, recombinants were
      found to be frequent ( approximately 17%) in natural populations of CMV-satRNA,
      and recombination may make an important contribution to the generation of new
      variants. To our knowledge this is the first report of data allowing the
      frequency of recombinant isolates in natural populations of an RNA replicon to be
      estimated.

PMID- 9010138
TI  - Analysis of orthologous retrovirus-like elements in the white-footed mouse,
      Peromyscus leucopus.
AB  - Three loci in the genome of the white-footed mouse, Peromyscus leucopus, were
      examined for the presence or absence of orthologous copies of the retrovirus-like
      element mys using polymerase chain reaction. We examined these loci in 28 mice
      collected throughout the P. leucopus species range. Mys insertions were present
      in only one of the individuals examined at the mys-1 and mys-7 loci. Conversely,
      the mys-6 element was found in several individuals, but the presence of this
      element was limited to northern latitudes. Because the long terminal repeats
      (LTRs) of a given element are expected to be identical at the time of
      retrotransposition into the genome, and to accumulate changes over evolutionary
      time, within-element LTR sequence comparisons can be used to estimate the
      relative age of insertions. Within-element LTR differences are greater in mys-6
      than in mys-1 or mys-7. The LTRs from orthologous mys-6 elements of six mice were
      sequenced. The alignment revealed 13 of the 22 differences between the right and
      left LTRs that were shared by all orthologous mys-6 sites, suggesting that
      relative to its time of insertion into the genome, mys-6 has only recently spread
      across the northern part of the species range.

PMID- 9010140
TI  - Structural comparisons of muscle and nonmuscle actins give insights into the
      evolution of their functional differences.
AB  - Actin is a highly conserved protein although many isoforms exist. In vertebrates
      and insects the different actin isoforms can be grouped by their amino acid
      sequence and tissue-specific gene expression into muscle and nonmuscle actins,
      suggesting that the different actins may have a functional significance. We ask
      here whether atomic models for G- and F-actins may help to explain this
      functional diversity. Using a molecular graphics program we have mapped the few
      amino acids that differ between isoactins. A small number of residues specific
      for muscle actins are buried in internal positions and some present a remarkable
      organization. Within the molecule, the replacements observed between muscle and
      nonmuscle actins are often accompanied by compensatory changes. The others are
      dispersed on the protein surface, except for a cluster located at the N-terminus
      which protrudes outward. Only a few of these residues specific for muscle actins
      are present in known ligand binding sites except the N-terminus, which has a
      sequence specific for each isoactin and is directly implicated in the binding to
      myosin. When we simulated the replacements of side chains of residues specific
      for muscle actins to those specific for nonmuscle actins, the N-terminus appears
      to be less compact and more flexible in nonmuscle actins. This would represent
      the first conformational grounds for proposing that muscle and nonmuscle actins
      may be functionally distinguishable. The rest of the molecule is very similar or
      identical in all the actins, except for a possible higher internal flexibility in
      muscle actins. We propose that muscle actin genes have evolved from genes of
      nonmuscle actins by substitutions leading to some conformational changes in the
      protruding N-terminus and the internal dynamics of the main body of the protein.

PMID- 9010141
TI  - Phylogenetic position of the mitochondrion-lacking protozoan Trichomonas tenax,
      based on amino acid sequences of elongation factors 1alpha and 2.
AB  - Major parts of amino-acid-coding regions of elongation factor (EF)-1alpha and EF
      2 in Trichomonas tenax were amplified by PCR from total genomic DNA and the
      products were cloned into a plasmid vector, pGEM-T. The three clones from each of
      the products of the EF-1alpha and EF-2 were isolated and sequenced. The insert
      DNAs of the clones containing EF-1alpha coding regions were each 1,185 bp long
      with the same nucleotide sequence and contained 53.1% of G + C nucleotides. Those
      of the clones containing EF-2 coding regions had two different sequences; one was
      2,283 bp long and the other was 2,286 bp long, and their G + C contents were 52.5
      and 52.9%, respectively. The copy numbers of the EF-1alpha and EF-2 gene per
      chromosome were estimated as four and two, respectively. The deduced amino acid
      sequences obtained by the conceptual translation were 395 residues from EF-1alpha
      and 761 and 762 residues from the EF-2s. The sequences were aligned with the
      other eukaryotic and archaebacterial EF-1alphas and EF-2s, respectively. The
      phylogenetic position of T. tenax was inferred by the maximum likelihood (ML)
      method using the EF-1alpha and EF-2 data sets. The EF-1alpha analysis suggested
      that three mitochondrion-lacking protozoa, Glugea plecoglossi, Giardia lamblia,
      and T. tenax, respectively, diverge in this order in the very early phase of
      eukaryotic evolution. The EF-2 analysis also supported the divergence of T. tenax
      to be immediately next to G. lamblia.

PMID- 9010142
TI  - Pyrophosphate and adenosine 5'-diphosphate synthesis from phospho(enol)pyruvate:
      catalysis by phosphate minerals and modulation by dimethyl sulfoxide.
AB  - Phospho(enol)pyruvate (PEP) undergoes transphosphorylation to form pyrophosphate
      (PPi) and adenosine 5'-diphosphate (5'-ADP) with high yields in the presence of
      an adsorbent surface of calcium phosphate (Pi.Ca), which is considered to be an
      ancient mineral with catalytic properties. PPi formation is a result of the
      phosphorolytic cleavage of the enol phosphate group of PEP by precipitated Pi.
      The synthesis of PPi is dependent on the amount of the solid matrix; it increases
      with the amount of adsorbed PEP and upon addition of dimethyl sulfoxide (Me2SO),
      a molecule with high dipolar moment. Although it is saturated with PEP at neutral
      pH, the phosphorylating Pi.Ca surface becomes effective only in alkaline
      conditions. In a parallel reaction, PEP phosphorylates 5'-AMP to 5'-ADP with a
      yield that is sevenfold higher in the presence of the Pi.Ca surface than in its
      absence, indicating that the solid matrix promotes interaction between adsorbed
      molecules with a high potential for phosphoryl transfer. In contrast to
      phosphorolysis, this latter reaction is stimulated by Me2SO only in homogeneous
      solution. It is concluded that phosphate minerals may have coadjuvated in
      reactions involving different phosphorylated compounds and that molecules with
      high dipolar moment may have acted in mildly alkaline, primitive aqueous
      environments to modulate phosphoryl transfer reactions catalyzed by phosphate
      minerals.

PMID- 9010143
TI  - Estimating the transition/transversion ratio from independent pairwise
      comparisons with an assumed phylogeny.
AB  - A method is presented for estimating the transition/transversion ratio (TI/TV),
      based on phylogenetically independent comparisons. TI/TV is a parameter of some
      models used in phylogeny estimation intended to reflect the fact that nucleotide
      substitutions are not all equally likely. Previous attempts to estimate TI/TV
      have commonly faced three problems: (1) few taxa; (2) nonindependence among
      pairwise comparisons; and (3) multiple hits make the apparent TI/TV between two
      sequences decrease over time since their divergence, giving a misleading
      impression of relative substitution probabilities. We have made use of the time
      dependency, modeling how the observed TI/TV changes over time and extrapolating
      to estimate the "instantaneous" TI/TV-the relevant parameter for phylogenetic
      inference. To illustrate our method, TI/TV was estimated for two mammalian
      mitochondrial genes. For 26 pairs of cytochrome b sequences, the estimate of
      TI/TV was 5.5; 16 pairs of 12s rRNA yielded an estimate of 9.5. These estimates
      are higher than those given by the maximum likelihood method and than those
      obtained by averaging all possible pairwise comparisons (with or without a two
      parameter correction for multiple substitutions). We discuss strengths,
      weaknesses, and further uses of our method.

PMID- 9010145
TI  - The risk of recurrent venous thromboembolism in patients with an Arg506-->Gln
      mutation in the gene for factor V (factor V Leiden).
AB  - BACKGROUND: A recently discovered mutation in coagulation factor V (Arg506-->Gln,
      referred to as factor V Leiden), which results in resistance to activated protein
      C, is found in approximately one fifth of patients with venous thromboembolism.
      However, the risk of recurrent thromboembolism in heterozygous carriers of this
      genetic abnormality is unknown. METHODS: We searched for factor V Leiden in 251
      unselected patients with a first episode of symptomatic deep-vein thrombosis
      diagnosed by venography. The patients were followed prospectively for a mean of
      3.9 years to determine the frequency of recurrent venous thrombosis and pulmonary
      embolism. RESULTS: Factor V Leiden was found in 41 of the patients (16.3 percent;
      95 percent confidence interval, 11.8 to 20.9 percent). The cumulative incidence
      of recurrent venous thromboembolism after follow-up of up to eight years was 39.7
      percent (95 percent confidence interval, 22.8 to 56.5 percent) among carriers of
      the mutation, as compared with 18.3 percent (95 percent confidence interval, 12.3
      to 24.3 percent) among patients without the mutation (hazard ratio, 2.4; 95
      percent confidence interval, 1.3 to 4.5; P<0.01). CONCLUSIONS: The risk of
      recurrent thromboembolic events is significantly higher in carriers of factor V
      Leiden than in patients without this abnormality. Large trials assessing the risk
      benefit ratio of long-term anticoagulation in carriers of the mutation who have
      had a first episode of venous thromboembolism are indicated.

PMID- 9010144
TI  - The duration of oral anticoagulant therapy after a second episode of venous
      thromboembolism. The Duration of Anticoagulation Trial Study Group.
AB  - BACKGROUND: A consensus has not been reached about the optimal duration of oral
      anticoagulant therapy after a second episode of venous thromboembolism. METHODS:
      In a multicenter trial, we compared six months of oral anticoagulant therapy with
      anticoagulant therapy continued indefinitely in patients who had had a second
      episode of venous thromboembolism. Of 227 patients enrolled, 111 were randomly
      assigned to six months of anticoagulation and 116 were assigned to receive
      anticoagulant therapy indefinitely; for both groups, the target international
      normalized ratio was 2.0 to 2.85. The initial episodes of deep-vein thrombosis (n
      = 193) and pulmonary embolism (n = 34), as well as recurrent episodes, were all
      objectively confirmed. RESULTS: After four years of follow-up, there were 26
      recurrences of venous thromboembolism that fulfilled the diagnostic criteria, 23
      in the group assigned to six months of therapy (20.7 percent) and 3 in the group
      assigned to continuing therapy (2.6 percent). The relative risk of recurrence in
      the group assigned to six months of therapy, as compared with the group assigned
      to therapy of indefinite duration, was 8.0 (95 percent confidence interval, 2.5
      to 25.9). There were 13 major hemorrhages, 3 in the six-month group, (2.7
      percent) and 10 in the infinite-treatment group (8.6 percent). The relative risk
      of major hemorrhage in the six-month group, as compared with the infinite
      treatment group was 0.3 (95 percent confidence interval, 0.1 to 1.1). There was
      no difference in mortality between the two groups. CONCLUSIONS: Prophylactic oral
      anticoagulation that was continued for an indefinite period after a second
      episode of venous thromboembolism was associated with a much lower rate of
      recurrence during four years of follow-up than treatment for six months. However,
      there was a trend toward a higher risk of major hemorrhage when anticoagulation
      was continued indefinitely.

PMID- 9010146
TI  - Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth
      and development factor on platelet counts after chemotherapy for lung cancer.
AB  - BACKGROUND: Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte
      growth and development factor (MGDF, also known as PEG-rHuMGDF), a recombinant
      molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and
      platelet production and reduces the severity of thrombocytopenia in animals
      receiving myelosuppressive chemotherapy. METHODS: We conducted a randomized,
      double-blind, placebo-controlled dose-escalation study of MGDF in 53 patients
      with lung cancer who were treated with carboplatin and paclitaxel. The patients
      were randomly assigned in blocks of 4 in a 1:3 ratio to receive either placebo or
      MGDF (0.03, 0.1, 0.3, 1.0, 3.0, or 5.0 microg per kilogram of body weight per
      day), injected subcutaneously. No other marrow-active cytokines were given.
      RESULTS: In the 38 patients who received MGDF after chemotherapy, the median
      nadir platelet count was 188,000 per cubic millimeter (range, 68,000 to 373,000),
      as compared with 111,000 per cubic millimeter (range, 21,000 to 307,000) in 12
      patients receiving placebo (P = 0.013). The platelet count recovered to base-line
      levels in 14 days in the treated patients as compared with more than 21 days in
      those receiving placebo (P<0.001). Among all 40 patients treated with MGDF, 1 had
      deep venous thrombosis and pulmonary embolism, and another had superficial
      thrombophlebitis. CONCLUSIONS: MGDF has potent stimulatory effects on platelet
      production in patients with chemotherapy-induced thrombocytopenia.

PMID- 9010147
TI  - Adult-onset idiopathic hypogonadotropic hypogonadism--a treatable form of male
      infertility.
AB  - BACKGROUND: Men with isolated gonadotropin-releasing hormone (GnRH) deficiency
      typically present with an absence of pubertal development. We describe an adult
      onset form of idiopathic hypogonadotropic hypogonadism that develops after
      puberty. METHODS: We studied 10 men (age, 27 to 57 years) with normal sexual
      maturation, idiopathic infertility, sexual dysfunction, low serum testosterone
      concentrations, and apulsatile secretion of luteinizing hormone on frequent blood
      sampling. All the men had otherwise normal anterior pituitary hormone secretion
      and sellar anatomy. We compared the results of semen analyses and measurements of
      testicular volume, serum testosterone, inhibin B, and gonadotropins in these men
      with the results in 24 men with classic GnRH deficiency before and during GnRH
      replacement therapy and in 29 normal men of similar age. RESULTS: Serum
      gonadotropin concentrations in the men with adult-onset GnRH deficiency were
      similar before and during pulsatile GnRH administration to those in the men with
      classic GnRH deficiency. However, as compared with men with classic GnRH
      deficiency, men with adult-onset hypogonadotropic hypogonadism had larger mean
      (+/-SD) testicular volumes (18+/-5 vs. 3+/-2 ml, P<0.001), serum testosterone
      concentrations (78+/-34 vs. 49+/-20 ng per deciliter [2.7+/-1.2 vs. 1.7+/-0.7
      nmol per liter], P=0.004), and serum inhibin B concentrations (119+/-52 vs. 60+/
      21 pg per milliliter, P<0.001). Treatment with GnRH reversed the hypogonadism and
      restored fertility in each of the five men who received long-term therapy.
      CONCLUSIONS: The recognition of adult-onset hypogonadotropic hypogonadism in men
      as a distinct disorder expands the spectrum of GnRH deficiency and identifies a
      treatable form of male infertility.

PMID- 9010148
TI  - Images in clinical medicine. Massive pulmonary embolism.

PMID- 9010149
TI  - Physician-assisted suicide and patients with human immunodeficiency virus
      disease.
AB  - BACKGROUND: Data are limited on the attitudes and practices of physicians
      regarding assisting the suicide of patients with human immunodeficiency virus
      (HIV) disease. METHODS: Between November 1994 and January 1995, we used an
      anonymous, self-administered questionnaire to survey all 228 physicians in the
      Community Consortium, an association of providers of health care to patients
      infected with HIV in the San Francisco Bay area. The responses were compared with
      those in a 1990 survey of consortium physicians. Physician-assisted suicide was
      defined as "a physician providing a sufficient dose of narcotics to enable a
      patient to kill himself." Respondents were to "assume that the patient is a
      mentally competent, severely ill individual facing imminent death." RESULTS: One
      hundred eighteen of the questionnaires were evaluated. Respondents reported a
      mean of 7.9 "direct" and 13.7 "indirect" requests from patients for assistance.
      In responses based on a case vignette, 48 percent of the physicians said they
      would be likely or very likely to grant the request of a patient with the
      acquired immunodeficiency syndrome (AIDS) for assistance in a suicide, as
      compared with 28 percent of the respondents in 1990. Asked to estimate the number
      of times they had granted the request of a patient with AIDS for assistance in
      committing suicide, 53 percent said they had done so at least once (mean number
      of times, 4.2; median, 1.0; range, 0 to 100). In a multivariate analysis, factors
      positively associated with having, in fact, assisted a suicide were having had a
      higher number of patients with AIDS who had died, a higher number of indirect
      requests from patients for assistance, a stated gay, lesbian, or bisexual
      orientation on the part of the physician, and a higher "intention to assist"
      score (as calculated from the physician's responses to the case vignette).
      CONCLUSIONS: Within a group of physicians caring for patients with HIV disease,
      the acceptance of assisted suicide increased between 1990 and 1995. A majority of
      respondents in 1995 said they had granted a request for assisted suicide from a
      patient with AIDS at least once.

PMID- 9010150
TI  - Procurement and allocation of solid organs for transplantation.

PMID- 9010151
TI  - Oral anticoagulant therapy for venous thromboembolism.

PMID- 9010152
TI  - Thrombopoietin--clinically realized?

PMID- 9010153
TI  - Allocating livers--devising a fair system.

PMID- 9010154
TI  - A piece of my mind. The road to Morrakonnam.

PMID- 9010155
TI  - Experts debate merits of 1-day opiate detoxification under anesthesia.

PMID- 9010156
TI  - Quality standards intend to bring psychiatry, primary care into closer
      collaboration.

PMID- 9010157
TI  - Radiologists learn results of new therapy trials, hear latest speculations on
      cause of old disorder.

PMID- 9010158
TI  - Protecting human subjects of biomedical research.

PMID- 9010159
TI  - From the Food and Drug Administration.

PMID- 9010160
TI  - From the Centers for Disease Control and Prevention. Recommended childhood
      immunization schedule--United States, 1997.

PMID- 9010161
TI  - When walking fails.

PMID- 9010162
TI  - When walking fails.

PMID- 9010163
TI  - Cost-effectiveness of intensive insulin therapy in the Diabetes Control and
      Complications Trial.

PMID- 9010164
TI  - Reporting cost-effectiveness analyses with confidence.

PMID- 9010165
TI  - The high cost of lost opportunities for prevention.

PMID- 9010166
TI  - Large trials vs meta-analysis of smaller trials.

PMID- 9010167
TI  - Large trials vs meta-analysis of smaller trials.

PMID- 9010168
TI  - Treatment of partial priapism with an intracavernous injection of etilefrine.

PMID- 9010169
TI  - Statewide quality improvement initiatives and mortality after cardiac surgery.
AB  - BACKGROUND: Recent reports from New York and northern New England claim that
      statewide quality improvement initiatives and outcome reporting are leading to
      decreased mortality following coronary artery bypass graft (CABG) surgery.
      OBJECTIVE: To compare trends in mortality after CABG surgery in Massachusetts (a
      state that has not instituted statewide outcome reporting) with the decreases
      reported from New York and northern New England. DESIGN: Surgical cohorts from
      1990, 1992, and 1994 were used to evaluate the risk-adjusted mortality trend for
      Massachusetts. We present this trend along with the published trends from New
      York and northern New England. For comparison, we also present unadjusted
      Medicare mortality trends from Massachusetts, New York, northern New England, and
      the entire United States. SETTING: All 12 Massachusetts hospitals performing
      cardiac surgery (excluding a Veterans Affairs hospital). PATIENTS AND DATA SETS:
      Massachusetts administrative data were used to identify all patients undergoing
      isolated CABG surgery in 1990, 1992, and 1994. MAIN OUTCOME MEASURES: Observed
      and risk-adjusted in-hospital mortality. RESULTS: Observed mortality rates in
      Massachusetts decreased from 4.7% in 1990 to 3.5% in 1992 and to 3.3% in 1994.
      The corresponding risk-adjusted mortality reductions for 1992 and 1994 (relative
      to 1990) were 35% and 42%, respectively. The mortality reduction seen in
      Massachusetts is comparable to the reductions seen in New York and northern New
      England over similar periods. Unadjusted Medicare mortality trends were generally
      similar in the states under study, and in the United States as a whole.
      CONCLUSIONS: In-hospital mortality after CABG surgery has decreased in
      Massachusetts despite the absence of statewide outcome reporting. Direct program
      evaluations are needed to better characterize the efficacy of the ongoing
      statewide outcome studies in New York and northern New England.

PMID- 9010170
TI  - Major depressive disorder in the 6 months after miscarriage.
AB  - OBJECTIVE: To test a priori hypotheses that miscarrying women are at increased
      risk for a first or recurrent episode of major depressive disorder in the 6
      months following loss and that this increased risk is greater for childless
      women, women with prior reproductive loss, and women aged 35 years or older; and
      to evaluate whether risk varies by time of gestation or by attitude toward the
      pregnancy. DESIGN: Cohort study. SETTING: The miscarriage cohort consisted of
      women attending a medical center for a spontaneous abortion (n=229); the
      comparison group was a population-based cohort of women drawn from the community
      (n=230). PARTICIPANTS: Miscarriage was defined as the involuntary termination of
      a nonviable intrauterine pregnancy before 28 completed weeks of gestation. Half
      of all participants were between 25 and 34 years of age; 40% were white and 35%
      Hispanic; 55% had more than a high school education. Participants constituted 60%
      of miscarrying women and 72% of community women who completed the first phase of
      this cohort study. MAIN OUTCOME MEASURE: Major depressive disorder was measured
      using the Diagnostic Interview Schedule. RESULTS: Risk for an episode of major
      depressive disorder among miscarrying women in the 6 months following loss was
      compared with the 6-month risk among community women who had not been pregnant in
      the preceding year. Among miscarrying women, 10.9% experienced an episode of
      major depressive disorder, compared with 4.3% of community women. The overall
      relative risk (RR) for an episode of major depressive disorder for miscarrying
      women was 2.5 (95% confidence interval [CI], 1.2-5.1) and was substantially
      higher for childless women (RR, 5.0; 95% CI, 1.7-14.4) than for women with
      children (RR, 1.3; 95% CI, 0.5-3.5) (P<.06). Among miscarrying women, 72% of
      cases of major depressive disorder began within the first month after loss; only
      20% of community cases started during the comparable period. Among miscarrying
      women with a history of major depressive disorder, 54% experienced a recurrence.
      However, RR did not vary significantly by history of prior reproductive loss or
      by maternal age, nor did risk vary by time of gestation or attitude toward the
      pregnancy. CONCLUSIONS: Physicians should monitor miscarrying women in the first
      weeks after reproductive loss, particularly women who are childless or who have a
      history of major depressive disorder. Where appropriate, supportive counseling or
      psychopharmacologic treatment should be considered.

PMID- 9010172
TI  - Outcomes and costs after hip fracture and stroke. A comparison of rehabilitation
      settings.
AB  - OBJECTIVE: To assess whether outcomes and costs differ for elderly patients
      admitted to rehabilitation hospitals, subacute nursing homes, and traditional
      nursing homes. DESIGN: Inception cohort stratified by provider type and followed
      prospectively for 6 months. SETTING: A total of 92 hospital-based units and
      freestanding facilities from 17 states. PATIENTS: A total of 518 randomly
      selected patients with hip fracture and 485 stroke patients admitted from
      November 1991 to February 1994. MAIN OUTCOME MEASURES: At 6 months comparing
      community residence, recovery to premorbid levels in 5 activities of daily living
      (ADLs), Medicare costs, and the number of therapy and physician visits. Outcomes
      were adjusted for premorbid residence and function, caregiver availability,
      comorbid illness, admission function, cognition, depression, sensory deficits,
      and mobility impairments. RESULTS: On admission, rehabilitation hospital patients
      were more likely (P<.001) to have caregivers and better cognitive and physical
      function. Hip fracture patients admitted to rehabilitation hospitals did not
      differ from patients admitted to nursing homes in returning to the community
      (adjusted odds ratio [OR], 1.3; 95% confidence interval [CI], 0.6-2.6) or in the
      number of ADLs recovered to premorbid level (difference, 0.09 ADL; 95% CI, -0.27
      0.44), but stroke patients admitted to rehabilitation hospitals were more likely
      to return to the community (adjusted OR, 3.3; 95% CI, 1.5-7.2) and recover ADLs
      (difference, 0.63 ADL; 95% CI, 0.20-1.07). Subacute nursing home patients with
      stroke were more likely than traditional nursing home patients to return to the
      community (adjusted OR, 6.8; 95% CI, 2.2-21.4), there was no difference in return
      to the community for patients with hip fracture (adjusted OR, 1.6; 95% CI, 0.7
      3.6), and there were no differences in recovery of ADLs for either condition.
      Medicare costs were greater (P<.001) for rehabilitation hospital patients than
      for subacute nursing home patients, and the costs for subacute nursing home
      patients were greater (P=.03 for stroke and .009 for hip fracture) than for
      traditional nursing home patients. CONCLUSIONS: Study findings are consistent
      with enhanced outcomes for elderly patients with stroke treated in rehabilitation
      hospitals but not for patients with hip fracture. Subacute nursing homes were
      more effective than traditional nursing homes in returning patients with stroke
      to the community, despite comparable functional outcomes.

PMID- 9010173
TI  - The legal and scientific basis for FDA's assertion of jurisdiction over
      cigarettes and smokeless tobacco.
AB  - On August 28, 1996, the US Food and Drug Administration (FDA) asserted
      jurisdiction over cigarettes and smokeless tobacco under the Federal Food, Drug,
      and Cosmetic Act. Under this Act, a product is a "drug" or "device" subject to
      FDA jurisdiction if it is "intended to affect the structure or any function of
      the body." The FDA determined that nicotine in cigarettes and smokeless tobacco
      does "affect the structure or any function of the body" because nicotine causes
      addiction and other pharmacological effects. The FDA then determined that these
      pharmacological effects are "intended" because (1) a scientific consensus has
      emerged that nicotine is addictive; (2) recent studies have shown that most
      consumers use cigarettes and smokeless tobacco for pharmacological purposes,
      including satisfying their addiction to nicotine; and (3) newly disclosed
      evidence from the tobacco manufacturers has revealed that the manufacturers know
      that nicotine causes pharmacological effects, including addiction, and design
      their products to provide pharmacologically active doses of nicotine. The FDA
      thus concluded that cigarettes and smokeless tobacco are subject to FDA
      jurisdiction because they contain a "drug," nicotine, and a "device" for
      delivering this drug to the body.

PMID- 9010171
TI  - School-based clusters of meningococcal disease in the United States. Descriptive
      epidemiology and a case-control analysis.
AB  - OBJECTIVE: To evaluate the epidemiologic features and risk factors for multiple
      cases of meningococcal disease in schools. DESIGN: Population-based prospective
      evaluation and case-control study of clusters of meningococcal disease that
      occurred in schools from January 1989 to June 1994. SETTING: Surveillance
      conducted through state health departments in the United States. MAIN OUTCOME
      MEASURES: Descriptive epidemiology of school-based clusters of meningococcal
      disease and determinants of their occurrence. RESULTS: We identified 22 clusters
      of meningococcal disease in 15 states. The estimated incidence of secondary
      meningococcal disease among schoolchildren aged 5 to 18 years was 2.5 per 100000
      population, a relative risk of 2.3 (95% confidence interval [CI], 1.6-3.3). The
      median number of students per cluster was 2 (range, 2-4). Of 30 subsequent cases,
      10 (33%) occurred 2 or fewer days after the index case, and 22 (73%) occurred 14
      or fewer days after the index case. Among the 8 schools with 2 or more cases, 50%
      of the additional cases occurred 2 or more days after the second case. Secondary
      schools (grades 7 through 12) accounted for 15 (75%) of 20 cluster schools
      compared with 9 (45%) of 20 matched control schools (P<.05). In 16 (73%) of 22
      clusters, interaction between case patients was noted. The index patient in
      cluster schools was more likely than the controls to have participated in a
      school-based group activity 14 or fewer days before illness (matched odds ratio,
      7.0; 95% CI, 0.9-57). CONCLUSIONS: Three quarters of the school clusters occurred
      in secondary schools, with over 70% of subsequent cases occurring within 2 weeks
      of the index case. Rapid initiation of a chemoprophylaxis program after 2 cases
      of meningococcal disease in a school would have potentially prevented 50% of
      subsequent cases in the clusters described.

PMID- 9010174
TI  - FDA regulation of tobacco advertising and youth smoking. Historical, social, and
      constitutional perspectives.
AB  - Perspectives on tobacco control in American society have shifted markedly. As the
      view that smoking as a voluntarily assumed health risk has declined, the social
      and political environment has become more conducive to industry regulation. This
      transformation can be traced to the mounting evidence of the health risks of
      secondary smoke; the addictive quality of nicotine; the vulnerability and
      exploitation of young people; and industry knowledge of the harmful effects of
      tobacco. Regulation of tobacco advertising and promotions by the Food and Drug
      Administration (FDA) raises serious concerns about constitutional protection for
      commercial speech. However, the minimal informational value of tobacco
      advertising suggests that it should be afforded a low level of constitutional
      protection. The FDA regulations impose reasonable "time, place, and manner"
      restrictions, leave open alternative channels of communication, restrict messages
      that are harmful to the public health, do not restrict political speech, prevent
      misleading messages, and help deter the unlawful sale of tobacco products to
      minors. The regulations meet the traditional criteria for regulating commercial
      speech, in that the government's asserted interest is strong, the agency's
      regulations directly advance that interest, and the regulations are no more
      extensive than necessary. Thus, the judiciary should defend the FDA's historical
      social and legislative mission to protect the public health.

PMID- 9010175
TI  - Can large-scale interventions improve care?

PMID- 9010177
TI  - Medicine and the arts.

PMID- 9010176
TI  - Babies are coming. Don't cap Medicaid.

PMID- 9010178
TI  - New computer techniques for medical illustration and scientific visualization.

PMID- 9010179
TI  - Hector Berlioz and Anton Chekhov: their passions in the balance.

PMID- 9010180
TI  - Plague and AIDS in literature.

PMID- 9010182
TI  - Reconstruction of massive bone defects with allograft in revision total knee
      arthroplasty.
AB  - Allograft bone was used to reconstruct a defect in the proximal aspect of the
      tibia or the distal aspect of the femur, or both, in thirty knees of twenty-eight
      patients who had a revision total knee arthroplasty. The average age of the
      patients at the time of the index procedure was 65.8 years (range, twenty-four to
      eighty-nine years). At an average of fifty months (range, twenty-four to 132
      months; median, thirty-six months) postoperatively, the score for twenty-three
      knees (twenty-one patients) had increased by at least 20 points, and these knees
      did not need additional operative treatment. Thus, the rate of success was 77 per
      cent. The procedure was considered a failure for the remaining seven knees
      because of infection (three), loosening of the tibial component (two), fracture
      of the graft (one), and non-union at the allograft-host junction (one). Properly
      applied allograft can be used to reconstruct massive bone defects, provide
      stability and support for implants, and restore bone stock in the event that
      additional operative treatment is necessary.

PMID- 9010181
TI  - Critical biological determinants of incorporation of non-vascularized cortical
      bone grafts. Quantification of a complex process and structure.
AB  - Our goal in this study was to evaluate the effects of and the interaction between
      the hypothesized principal determinants of the incorporation of grafts:
      antigenicity and treatment of the graft. We implanted fresh and frozen cortical
      bone grafts that were matched for both major and non-major histocompatibility
      complex antigens (syngeneic grafts), matched for major but not for non-major
      histocompatibility complex antigens (minor mismatch), and mismatched for both
      major and non-major histocompatibility complex antigens (major mismatch). We used
      a rat model with an eight-millimeter segmental defect in the femur. The construct
      was stabilized with a plastic plate, threaded Kirschner wires, and cerclage
      wires. We evaluated the grafts at one, two, and four months after implantation.
      We measured the immune response; assessed the incorporation of the graft with use
      of histological examination, biomechanical testing, and quantitative isotopic
      kinetics; and statistically analyzed the effects of and the interactions among
      three independent variables: time, the degree of matching for major
      histocompatibility complex antigens, and the treatment of the graft (whether it
      was fresh or frozen). These three independent variables had profound effects on
      the pattern, rate, and quality of the incorporation of the graft. Two-way and
      three-way interactions among these variables were also noted. Serial changes in
      every dependent variable were observed with time. Systemic antibody specific for
      donor antigens was measurable only in the serum of animals that had a major
      mismatch, but freezing markedly attenuated the systemic antibody response.
      Revascularization was profoundly affected by histocompatibility-antigen matching;
      the syngeneic grafts were revascularized more quickly and to a greater degree
      than the grafts with either a minor or a major mismatch. Freezing significantly
      (p < 0.001) reduced the revascularization of the syngeneic grafts but had no
      discernible effect on the grafts with a minor mismatch.

PMID- 9010183
TI  - Arthrodesis of the knee with a modular titanium intramedullary nail.
AB  - We retrospectively studied the results of arthrodesis of the knee with a modular
      titanium intramedullary nail that couples at the knee. The study group consisted
      of thirteen patients who had a malignant tumor around the knee, five who had
      failure of a total knee arthroplasty, and three who had a locally destructive
      benign tumor about the knee. All of the patients were followed for a minimum of
      two years. Through a single incision at the knee, one nail was inserted
      retrograde into the femur and the other, antegrade into the tibia; the two nails
      were joined at the level of the knee by a conical couple and were secured with
      locking screws. The diameters of the nails were different, to accommodate the
      dissimilar sizes of the tibial and femoral intramedullary canals. A solid osseous
      fusion was achieved in nineteen (90 per cent) of the twenty-one patients (sixteen
      who had had resection of a tumor and three who had had a failed arthroplasty), at
      an average of 8.4 months (range, three to nineteen months) after the operation.
      One patient had a delayed union, but fusion was achieved after additional bone
      grafting. Of the sixteen patients who were available for clinical and
      radiographic evaluation at the time of the study, fifteen were satisfied with the
      over-all outcome and thirteen had either less pain or the same amount of pain as
      they had had preoperatively. There were no mechanical failures of the implant and
      no recurrences of tumor. Complications occurred in eight (38 per cent) of the
      twenty-one patients: three patients had a stress fracture, three had a peroneal
      nerve palsy (one of which was transient), one had a superficial wound infection,
      and one had reflex sympathetic dystrophy.

PMID- 9010184
TI  - Infection around joint replacements in patients who have a renal or liver
      transplantation.
AB  - The results of thirty-five joint (hip or knee) replacements in nineteen patients
      who had an organ transplantation were retrospectively reviewed. The patients
      received a standard immunosuppressive induction regimen at the time of the
      transplantation and were maintained on a combination of prednisone, azathioprine,
      and cyclosporine A. All patients received antibiotics perioperatively, but
      antibiotic-impregnated bone cement was not used for any procedure. Six joint
      replacements, in three patients who were an average of 48.2 years old at the time
      of the arthroplasty, were performed before a renal transplantation. Twenty-four
      joint replacements, in fourteen patients who were an average of 40.9 years old at
      the time of the arthroplasty, were performed after an organ transplantation. Two
      patients, who were an average of 53.8 years old at the time of the arthroplasty,
      each had a joint replacement both before and after a liver transplantation (a
      total of five joint replacements). The average duration of follow-up from the
      first joint replacement was 8.8 years (range, one to twenty-three years). The
      Harris hip score or The Hospital for Special Surgery knee score was determined at
      the time of the latest follow-up examination. An infection developed around the
      implant in five patients who had had the joint replacement after a
      transplantation. The average interval from implantation of the prosthesis until
      detection of the infection was 3.4 years (range, one to six years). One patient
      who had a liver transplant was infected with Pseudomonas aeruginosa and another
      one was infected with Escherichia coli. One patient who had a renal transplant
      was infected with Staphylococcus epidermidis; one, with Enterococcus; and one,
      with Serratia marcescens. We found that patients who had a joint replacement
      after an organ transplantation had a very high risk of devastating infection. The
      rate of such infection was 19 per cent (five of twenty-seven joint replacements
      in sixteen patients).

PMID- 9010185
TI  - Total hip arthroplasty with cement for juvenile rheumatoid arthritis. Results at
      a minimum of ten years in patients less than thirty years old.
AB  - We retrospectively reviewed the clinical and radiographic results of total hip
      arthroplasty with cement in patients with juvenile rheumatoid arthritis who were
      less than thirty years old at the time of the index procedure. Thirty-nine
      patients (sixty-six hips) were managed with this procedure at our institution
      between 1971 and 1983. Six patients (eleven hips) died before a minimum of ten
      years of follow-up; the remaining thirty-three patients (fifty-five hips) were
      followed for at least eleven years. Twenty-eight patients (forty-six hips) had at
      least one original component in situ after an average duration of clinical follow
      up of 15.1 years, and twenty-three of these patients (thirty-eight hips) were
      followed radiographically for an average of 14.7 years. At the time of the latest
      follow-up examination, all twenty-eight patients were able to walk outside the
      home; twenty of these patients (thirty-five hips; 76 per cent) had no pain with
      activity, and eight patients (eleven hips; 24 per cent) had mild-to-moderate pain
      with activity. Over-all, twelve (18 per cent) of the sixty-six femoral components
      and twenty-three (35 per cent) of the sixty-six acetabular components were
      revised after an average of 12.8 and 11.8 years, respectively. The fifteen-year
      survival rate for the femoral components was 85 per cent with revision or
      radiographic loosening as the end point. The fifteen-year survival rate for the
      acetabular components was 70 per cent with revision as the end point and 61 per
      cent with revision or radiographic loosening as the end point. The benefits of
      total hip arthroplasty were maintained over the long term in most of our patients
      who had juvenile rheumatoid arthritis. However, the durability of the components
      in these young patients remains a concern.

PMID- 9010186
TI  - Charnley total hip arthroplasty with use of improved techniques of cementing. The
      results after a minimum of fifteen years of follow-up.
AB  - Three hundred and fifty-seven consecutive Charnley total hip arthroplasties were
      performed in 320 patients with use of a so-called second-generation technique of
      cementing between July 1976 and June 1978. This technique includes use of a
      distal femoral intramedullary cement plug, hand-mixing of the cement, and use of
      a cement gun to deliver the cement into the femoral canal in a retrograde
      fashion. At the time of the latest follow-up evaluation, a minimum of fifteen
      years after the arthroplasty, 130 patients (142 hips) were still alive, 189
      patients (214 hips) had died, and one patient (one hip) had been lost to follow
      up. A radiograph was made for 116 (82 per cent) of the 142 hips in the 130
      surviving patients. Of the 356 hips that had not been lost to follow-up, thirty
      three (9 per cent) had had a revision and two (1 per cent), a Girdlestone
      resection arthroplasty during the follow-up period. Nineteen hips (5 per cent)
      were revised because of aseptic loosening of the femoral or acetabular component,
      or both (two hips); seven (2 per cent), because of loosening with infection; and
      seven (2 per cent), because of dislocation. The two resection arthroplasties were
      performed because of loosening with infection; both were done in patients who
      died before the time of the latest follow-up evaluation. Of the 142 hips in the
      130 patients who were alive at a minimum of fifteen years, twenty-two (15 per
      cent) had been revised: fifteen (11 per cent), because of aseptic loosening;
      three (2 per cent), because of loosening with infection; and four (3 per cent),
      because of dislocation. Revision of the femoral component because of aseptic
      loosening (excluding components that were revised because of dislocation or
      infection) was performed in four (1 per cent) of the entire series of 356 hips
      and in three (2 per cent) of the 142 hips in the 130 patients who survived for at
      least fifteen years. Two of the 356 hips and two of the 142 hips had aseptic
      loosening of the acetabular as well as the femoral component at the time of the
      revision. Loosening of the femoral component, defined as aseptic loosening
      leading to revision or as definite or probable radiographic loosening, occurred
      in ten (3 per cent) of the 356 hips and in six (5 per cent) of the 116 hips for
      which radiographs were made at a minimum of fifteen years. The acetabular
      component was revised because of aseptic loosening in seventeen (5 per cent) of
      the entire series of 356 hips and in fourteen (10 per cent) of the 142 hips in
      the 130 patients who survived for at least fifteen years. The acetabular
      component loosened without infection in forty-one (12 per cent) of the 356 hips
      and in twenty-six (22 per cent) of the 116 hips for which radiographs were made
      at a minimum of fifteen years. In two of these patients, the femoral component
      was also revised. Thus, of the entire series of 356 hips, two had a revision of
      the femoral component alone because of aseptic loosening; fifteen, a revision of
      the acetabular component alone; and two, a revision of both components. Of the
      142 hips in the 130 patients who survived for at least fifteen years, one was
      revised for loosening of the femoral component alone; twelve, for loosening of
      the acetabular component alone; and two, for loosening of both components. These
      findings demonstrate long-term durability of fixation of the femoral component
      but less reliable fixation of the acetabular component, even when the surgeon is
      experienced and improved techniques of cementing are used.

PMID- 9010187
TI  - Postaxial type-B polydactyly. Prevalence and treatment.
AB  - A prospective screening program of 11,161 newborns identified twenty-one infants
      who had postaxial type-B polydactyly (a prevalence of one in 531 live births).
      Sixteen infants (76 per cent) had bilateral postaxial type-B polydactyly.
      Eighteen infants (86 per cent) had a family history of the anomaly. The racial
      prevalence was one in 143 live births of black infants and one in 1339 live
      births of white infants. The duplicated small fingers were treated in the newborn
      nursery with suture ligation at the base of the pedicle. One infant had a second
      procedure to remove a blackened digit that remained firmly attached one month
      after the initial treatment. No other complications occurred. Fifteen patients
      (twenty-eight fingers) were reexamined at an average age of twenty months (range,
      twelve to thirty-seven months). Twelve fingers (43 per cent) had a residual bump,
      with an average diameter of two millimeters (range, one to six millimeters).
      Despite the residual bumps, all of the parents were satisfied with the cosmetic
      result.

PMID- 9010188
TI  - Anterior decompression and stabilization with the Kaneda device for thoracolumbar
      burst fractures associated with neurological deficits.
AB  - One hundred and fifty consecutive patients who had a burst fracture of the
      thoracolumbar spine and associated neurological deficits were managed with a
      single-stage anterior spinal decompression, strut-grafting, and Kaneda spinal
      instrumentation. At a mean of eight years (range, five years to twelve years and
      eleven months) after the operation, radiographs showed successful fusion of the
      injured spinal segment in 140 patients (93 per cent). Ten patients had a
      pseudarthrosis, and all were managed successfully with posterior spinal
      instrumentation and a posterolateral arthrodesis. The percentage of the canal
      that was obstructed, as measured on computed tomography, improved from a
      preoperative mean of 47 per cent (range, 24 to 92 per cent) to a postoperative
      mean of 2 per cent (range, 0 to 8 per cent). Despite breakage of the Kaneda
      device in nine patients, removal of the implant was not necessary in any patient.
      None of the patients had iatrogenic neurological deficits. After the anterior
      decompression, the neurological function of 142 (95 per cent) of the 150 patients
      improved by at least one grade, as measured with a modification of the grading
      scale of Frankel et al. Fifty-six (72 per cent) of the seventy-eight patients who
      had preoperative paralysis or dysfunction of the bladder recovered completely.
      One hundred and twenty-five (96 per cent) of the 130 patients who were employed
      before the injury returned to work after the operation, and 112 (86 per cent) of
      them returned to their previous job without restrictions. We concluded that
      anterior decompression, strut-grafting, and fixation with the Kaneda device in
      patients who had a burst fracture of the thoracolumbar spine and associated
      neurological deficits yielded good radiographic and functional results.

PMID- 9010189
TI  - Colonna arthroplasty with concomitant femoral shortening and rotational
      osteotomy. Long-term results.
AB  - The results of Colonna capsular arthroplasty in twenty-two hips in twenty
      patients were reviewed. All twenty patients were at least five years old at the
      time of the operation, which was performed for either complete dislocation or
      marked subluxation of the hip. None were candidates for reconstructive procedures
      designed to preserve articular cartilage. The mean age at the time of the Colonna
      arthroplasty was nine years and three months (range, five years to fifteen years
      and two months), and the mean duration of follow-up was sixteen years (range, six
      to thirty-two years). At the most recent follow-up examination, the mean Harris
      hip score, for the twenty-one hips for which it was available, was 82 points
      (range, 52 to 98 points), the patients had improved gait, and there was marked
      improvement in the radiographic appearance of the hip according to the
      classification system of Severin. Thirteen hips in twelve patients had
      concomitant femoral shortening and rotational osteotomy at the time of the
      Colonna arthroplasty, and none of these patients who did not have evidence of
      avascular necrosis of the capital femoral epiphysis preoperatively had it
      postoperatively. Three hips that did not have concomitant femoral shortening had
      evidence of new-onset avascular necrosis after the Colonna arthroplasty.
      Concomitant femoral shortening and rotational osteotomy allowed the operation to
      be performed without preoperative traction, dramatically reduced the need for a
      subsequent rotational femoral osteotomy, and reduced the prevalence of
      postoperative avascular necrosis of the capital femoral epiphysis.

PMID- 9010190
TI  - The results of transplantation of intercalary allografts after resection of
      tumors. A long-term follow-up study.
AB  - We reviewed the results of 104 intercalary allograft procedures that had been
      performed, between April 1974 and August 1992, in 100 patients, usually after
      resection of a segment of bone because of an osseous neoplasm. The median
      duration of follow-up was 5.6 years. Retention of the graft and return to
      essentially normal function were the measures of success and, on that basis,
      eighty-seven (84 per cent) of the 104 reconstructions were successful. Of the
      fifteen limbs in which the reconstruction failed, four were salvaged with
      insertion of a second allograft and three, with use of some other technique. Of
      the 104 allograft procedures, eight (including two in patients who had a
      recurrent tumor) were followed by an amputation; thus, the ultimate rate of
      salvage was 92 per cent for the entire series. Thirty-one grafts failed to unite
      at one junction with the host or both, within one year after the operation, and
      this necessitated eighty-one additional operative procedures to achieve a good
      result. Life-table regression analysis showed that age, gender, anatomical site,
      and length of the graft were not associated with significant differences in the
      over-all outcome. Infection (p = 0.0001); fracture (p = 0.002); stage of the
      lesion (p = 0.007); and use of adjuvant chemotherapy or radiation, or both (p =
      0.008), all had an adverse effect on the survival of the allograft. Despite the
      relatively high rate of non-union that necessitated additional operations, these
      data indicate that transplantation of allografts for the treatment of intercalary
      defects has a high rate of success and usually results in a functional limb.

PMID- 9010192
TI  - Entrapment of the bladder in an acetabular fracture. A case report.

PMID- 9010191
TI  - Suppression of osteoblast function by titanium particles.
AB  - In order to understand the effect of particulate debris on osteoblast function,
      we studied the effect of different particles, including titanium and polystyrene,
      on bone collagen mRNA (messenger RNA) with the use of Northern blot hybridization
      analysis, and we studied the effect of the particles on the biosynthesis of bone
      collagen with analysis of 3H-proline incorporation and with the Western blot
      technique. The steady-state levels of mRNA for procollagens alpha1(I) and
      alpha1(III) were markedly suppressed in human MG-63 osteoblast-like cells exposed
      to phagocytosable titanium particles that were smaller than three micrometers.
      Both titanium and polystyrene particles smaller than three micrometers suppressed
      the expression of the gene that codes for collagen, and the suppression of the
      expression of the gene was related to the size but not to the composition of the
      particles. The biosynthesis of both type-I and type-III collagen also was
      decreased in cells that had been treated with titanium particles. Neither the
      viability nor the proliferation of cells was affected by particulate debris.
      These data indicate that phagocytosable titanium particles can significantly
      suppress the expression of the gene that codes for collagen in osteoblast-like
      cells (p < 0.05).

PMID- 9010193
TI  - Fracture of a ceramic femoral head after a revision operation. A case report.

PMID- 9010194
TI  - Fractures of the forearm complicated by palsy of the anterior interosseous nerve
      caused by a constrictive dressing. A report of four cases.

PMID- 9010195
TI  - Managed care: form, function, and evolution.

PMID- 9010196
TI  - Illusion of an anomalous insertion.

PMID- 9010197
TI  - Detailed description of anomaly.

PMID- 9010198
TI  - Neural stem cells are blasting off.

PMID- 9010199
TI  - Systems of memory in the human brain.

PMID- 9010200
TI  - mRNA localization in neurons: a multipurpose mechanism?

PMID- 9010201
TI  - Molecular genetics of demyelination: new wrinkles on an old membrane.

PMID- 9010202
TI  - Pre- and postfusion regulation of transmitter release.

PMID- 9010203
TI  - Mice lacking p35, a neuronal specific activator of Cdk5, display cortical
      lamination defects, seizures, and adult lethality.
AB  - The adult mammalian cortex is characterized by a distinct laminar structure
      generated through a well-defined pattern of neuronal migration. Successively
      generated neurons are layered in an "inside-out" manner to produce six cortical
      laminae. We demonstrate here that p35, the neuronal-specific activator of cyclin
      dependent kinase 5, plays a key role in proper neuronal migration. Mice lacking
      p35, and thus p35/cdk5 kinase activity, display severe cortical lamination
      defects and suffer from sporadic adult lethality and seizures. Histological
      examination reveals that the mutant mice lack the characteristic laminated
      structure of the cortex. Neuronal birth-dating experiments indicate a reversed
      packing order of cortical neurons such that earlier born neurons reside in
      superficial layers and later generated neurons occupy deep layers. The phenotype
      of p35 mutant mice thus demonstrates that the formation of cortical laminar
      structure depends on the action of the p35/cdk5 kinase.

PMID- 9010204
TI  - floating head and masterblind regulate neuronal patterning in the roof of the
      forebrain.
AB  - The epiphysial region of the dorsal diencephalon is the first site at which
      neurogenesis occurs in the roof of the zebrafish forebrain. We show that the
      homeobox containing gene floating head (flh) is required for neurogenesis to
      proceed in the epiphysis. In flh- embryos, the first few epiphysial neurons are
      generated, but beyond the 18 somite stage, neuronal production ceases. In
      contrast, in masterblind- (mbl-) embryos, epiphysial neurons are generated
      throughout the dorsal forebrain. We show that mbl is required to prevent the
      expression of flh in dorsal forebrain cells rostral to the epiphysis.
      Furthermore, epiphysial neurons are not ectopically induced in mbl-/flh- embryos,
      demonstrating that the epiphysial phenotype of mbl- embryos is mediated by
      ectopic Flh activity. We propose a role for Flh in linking the signaling pathways
      that regulate regional patterning to the signaling pathways that regulate
      neurogenesis.

PMID- 9010205
TI  - Assembly of CNS myelin in the absence of proteolipid protein.
AB  - Two proteolipid proteins, PLP and DM20, are the major membrane components of
      central nervous system (CNS) myelin. Mutations of the X-linked PLP/DM20 gene
      cause dysmyelination in mouse and man and result in significant mortality. Here
      we show that mutant mice that lack expression of a targeted PLP gene fail to
      exhibit the known dysmyelinated phenotype. Unable to encode PLP/DM20 or PLP
      related polypeptides, oligodendrocytes are still competent to myelinate CNS axons
      of all calibers and to assemble compacted myelin sheaths. Ultrastructurally,
      however, the electron-dense 'intraperiod' lines in myelin remain condensed,
      correlating with its reduced physical stability. This suggests that after myelin
      compaction, PLP forms a stabilizing membrane junction, similar to a "zipper."
      Dysmyelination and oligodendrocyte death emerge as an epiphenomenon of other PLP
      mutations and have been uncoupled in the PLP null allele from the risk of
      premature myelin breakdown.

PMID- 9010206
TI  - Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in
      mice lacking mGluR1.
AB  - Most of the cerebellar Purkinje cells (PCs) of an adult animal are innervated
      individually by a single climbing fiber (CF) that forms strong excitatory
      synapses with the PCs. This one-to-one relationship between a PC and a CF is a
      consequence of a developmentally regulated regression of the innervation of PCs
      by CFs. We found that, in mice deficient in the type 1 metabotropic glutamate
      receptor (mGluR1), the regression of supernumerary CFs ceases by the end of the
      second postnatal week, which is about one week earlier than in normal mice.
      Consequently, about one third of PCs in the mGluR1 mutant mice are innervated by
      multiple CFs in adulthood. We conclude that the regression of CFs normally occurs
      in two developmental phases and that mGluR1 plays a crucial role in the second
      phase.

PMID- 9010207
TI  - FGF2 concentration regulates the generation of neurons and glia from multipotent
      cortical stem cells.
AB  - The embryonic cerebral cortex contains a population of stem-like founder cells
      capable of generating large, mixed clones of neurons and glia in vitro. We report
      that the default state of early cortical stem cells is neuronal, and that stem
      cells are heterogeneous in the number of neurons that they generate. In low
      fibroblast growth factor (FGF2) concentrations, most maintain this specification,
      generating solely neuronal progeny. Oligodendroglial production within these
      clones is stimulated by a higher, threshold level of FGF2, and astrocyte
      production requires additional environmental factors. Because most cortical
      neurons are born before glia in vivo, these data support a model in which the
      scheduled production of cortical cells involves an intrinsic neuronal program in
      the early stem cells and exposure to environmental, glia-inducing signals.

PMID- 9010208
TI  - Requirement for the PDZ domain protein, INAD, for localization of the TRP store
      operated channel to a signaling complex.
AB  - In Drosophila, the store-operated Ca2+ channel, TRP, is required in photoreceptor
      cells for a sustained response to light. Here, we show that TRP forms a complex
      with phospholipase C-beta (NORPA), rhodopsin (RH1), calmodulin, and the PDZ
      domain containing protein INAD. Proteins with PDZ domains have previously been
      shown to cluster ion channels in vitro. We show that in InaD mutant flies, TRP is
      no longer spatially restricted to its normal subcellular compartment, the
      rhabdomere. These results provide evidence that a PDZ domain protein is required,
      in vivo, for anchoring of an ion channel to a signaling complex. Furthermore,
      disruption of this interaction results in retinal degeneration. We propose that
      the TRP channel is linked to NORPA and RH1 to facilitate feedback regulation of
      these upstream signaling molecules.

PMID- 9010209
TI  - unc-8, a DEG/ENaC family member, encodes a subunit of a candidate mechanically
      gated channel that modulates C. elegans locomotion.
AB  - Mechanically gated ion channels are important modulators of coordinated movement,
      yet little is known of their molecular properties. We report that C. elegans unc
      8, originally identified by gain-of-function mutations that induce neuronal
      swelling and severe uncoordination, encodes a DEG/ENaC family member homologous
      to subunits of a candidate mechanically gated ion channel. unc-8 is expressed in
      several sensory neurons, interneurons, and motor neurons. unc-8 null mutants
      exhibit previously unrecognized but striking defects in the amplitude and
      wavelength of sinusoidal tracks inscribed as they move through an E. coli lawn.
      We hypothesize that UNC-8 channels could modulate coordinated movement in
      response to body stretch. del-1, a second DEG/ENaC family member coexpressed with
      unc-8 in a subset of motor neurons, might also participate in a channel that
      contributes to nematode proprioception.

PMID- 9010210
TI  - Local Ca2+ release from internal stores controls exocytosis in pituitary
      gonadotrophs.
AB  - Exocytosis and the cell-averaged cytosolic [Ca2+], [Ca2+]i, were tracked in
      single gonadotrophs. Cells released 100 granules/s at 1 microM = [Ca2+]i when
      gonadotropin-releasing hormone (GnRH) activated IP3-mediated Ca2+ release from
      internal stores, but only 1 granule/s when [Ca2+]i was raised uniformly to 1
      microM by other means. Strong exocytosis was then seen only at higher [Ca2+]i
      (half-maximal at 16 microM). Parallel second messengers did not contribute to
      GnRH-induced exocytosis, because IP3 alone was as effective as GnRH, and because
      even GnRH failed to trigger rapid exocytosis when the [Ca2+]i rise was blunted by
      EGTA. When [Ca2+]i was released from stores, exocytosis depended on [Ca2+]i
      rising rapidly, as if governed by Ca2+ flux into the cytosol. We suggest that IP3
      releases Ca2+ selectively from subsurface cisternae, raising [Ca2+] near exocytic
      sites 5-fold above the cell average.

PMID- 9010211
TI  - Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent
      electrostatic switch.
AB  - Synaptotagmin I is a synaptic vesicle protein that is thought to act as a Ca2+
      sensor in neurotransmitter release. The first C2 domain of synaptotagmin I (C2A
      domain) contains a bipartite Ca2+-binding motif and interacts in a Ca2+-dependent
      manner with syntaxin, a central component of the membrane fusion complex.
      Analysis by nuclear magnetic resonance spectroscopy and site-directed mutagenesis
      shows that this interaction is mediated by the cooperative action of basic
      residues surrounding the Ca2+-binding sites of the C2A domain and is driven by a
      change in the electrostatic potential of the C2A domain induced by Ca2+ binding.
      A model is proposed whereby synaptotagmin acts as an electrostatic switch in Ca2+
      triggered synaptic vesicle exocytosis, promoting a structural rearrangement in
      the fusion machinery that is effected by its interaction with syntaxin.

PMID- 9010212
TI  - GABA(B)-mediated presynaptic inhibition of excitatory transmission and synaptic
      vesicle dynamics in cultured hippocampal neurons.
AB  - Local recycling of synaptic vesicle membrane at nerve terminals is necessary to
      maintain a readily releasable pool of transmitter. To what extent are the
      dynamics of vesicle recycling subject to modulation? We examined the influence of
      presynaptic GABA(B) receptors on vesicle dynamics at single synapses using
      optical imaging of FM1-43 in cultured rat hippocampal neurons. The kinetics of
      FM1-43 destaining indicate that synapses from a single neuron have a unimodal
      distribution of release probabilities, and GABA(B)-mediated inhibition occurs
      uniformly at all sites. Electrical and optical recordings from single cells show
      that the inhibition of excitatory transmission is entirely accounted for by a
      rapidly reversible reduction of exocytosis. In contrast, GABA(B) receptors do not
      alter the rate or extent of endocytosis.

PMID- 9010213
TI  - Identification of functionally distinct isoforms of the N-type Ca2+ channel in
      rat sympathetic ganglia and brain.
AB  - The N channel is critical for regulating release of neurotransmitter at many
      synapses, and even subtle differences in its activity would be expected to
      influence the efficacy of synaptic transmission. Although several splice variants
      of the N channel are expressed in the mammalian nervous system, their biological
      importance is presently unclear. Here, we show that variants of the alpha1B
      subunit of the N channel are expressed in sympathetic ganglia and that
      alternative splicing within IIIS3-S4 and IVS3-S4 generate kinetically distinct
      channels. We further show a striking difference between the expression pattern of
      the S3-S4 variants in brain and peripheral ganglia and conclude that the brain
      dominant form of the N channel gates 2-to-4-fold more rapidly than that
      predominant in ganglia.

PMID- 9010214
TI  - Coupling of permeation and gating in an NMDA-channel pore mutant.
AB  - We report a strong coupling between permeation and gating in a mutant NMDA
      channel (NR1 N598Q-NR2A). The channel opens to two states that differ by their
      conductance and, surprisingly, by their selectivity for two permeant monovalent
      cations, Na+ and Cs+. The two open states are linked to the closed state via a
      cyclic gating reaction that proceeds preferentially in one direction under
      biionic conditions, indicating that the gating mechanism is not at equilibrium.
      The direction and the magnitude of this gating asymmetry can be accounted for by
      assuming that ions bound to a site in the permeation pathway influence the gating
      of this mutant channel, and that in the closed state, the channel site is
      accessible to internal cations.

PMID- 9010215
TI  - R-Ras is regulated by activators and effectors distinct from those that control
      Ras function.
AB  - Like Ras, constitutively activated mutants of the Ras-related protein R-Ras cause
      tumorigenic transformation of NIH3T3 cells. However, since R-Ras causes a
      transformed phenotype distinct from that induced by Ras, it is likely that R-Ras
      controls signaling pathways and cellular processes distinct from those regulated
      by Ras. To address this possibility, we determined if R-Ras is regulated by
      activators and effectors distinct from those that regulate Ras function. We
      observed that Ras guanine nucleotide exchange factors failed to activate R-Ras in
      vivo, indicating that R-Ras is activated by distinct GEFs. Consistent with this,
      mutants of R-Ras with mutations analogous to the Ras(15A)/(17N) dominant negative
      proteins did not antagonize Ras GEF function and lacked the growth inhibitory
      activity seen with these mutant Ras proteins. Thus, R-Ras, but not Ras, is
      dispensable for the viability of NIH3T3 cells. Finally, whereas constitutively
      activated Ras can overcome the growth inhibitory action of the Ras(17N) dominant
      negative protein via Raf-dependent and -independent activities, transforming
      mutants of R-Ras failed to do so. This inability was consistent with our
      observation that Ras-, but not R-Ras-transformed, NIH3T3 cells possessed
      constitutively upregulated Raf kinase activities. Thus, R-Ras and Ras are
      regulators of distinct signaling pathways and cellular processes.

PMID- 9010216
TI  - PACT: cloning and characterization of a cellular p53 binding protein that
      interacts with Rb.
AB  - Cellular functions of tumor suppressor proteins can be mediated by protein
      protein interactions. Using p53 as a probe to screen an expression library, a
      cDNA encoding a 250 kDa protein was isolated. Recombinant forms of this protein,
      designated PACT, bind to wild type p53 while two different mutations abolish this
      interaction. PACT protein can also interfere with p53 specific DNA binding. PACT
      contains a serine/arginine (SR) rich region and a C' terminal lysine rich domain.
      The 250 kDa PACT protein can be precipitated from cell lysates by a method
      specific for SR proteins. snRNPs can be co-immunoprecipitated from cells with
      anti-PACT antibodies. These antibodies stain cell nuclei in a speckled pattern
      reminiscent of the distribution of known splicing factors. Recently, RBQ1, a
      truncated human homologue of PACT was identified by virtue of Rb binding. We show
      that RBQ1 is truncated as a result of a possible mutational event. PACT can
      interact with both cellular Rb and p53.

PMID- 9010217
TI  - Oncogenic activation of the alphaPDGFR defines a domain that negatively regulates
      receptor dimerization.
AB  - The alpha platelet derived growth factor receptor (alphaPDGFR) extracellular
      Immunoglobulin (Ig) like domains 1-3 contain major determinants for ligand
      interaction. We now report that a deletion of Ig-like loop 3, but not Ig-like
      loop 1 or 2, of the alphaPDGFR causes ligand-independent transformation in NIH3T3
      cells. Biochemical analyses of alphaPDGFR mutants lacking Ig-like loop 3 indicate
      that cellular transformation is mediated by ligand-independent activation of the
      alphaPDGFR tyrosine kinase activity as determined by receptor autophosphorylation
      both in vivo and in vitro. Moreover, cross-linking analysis of alphaPDGFR mutants
      expressed ectopically in NIH3T3 cells indicate that deletion within extracellular
      domain 3 leads to ligand-independent receptor dimerization. All of these findings
      suggest that the Ig-like loop 3 of the alphaPDGFR contains the major determinants
      which inhibit receptor dimerization in the quiescent cells and that the ligand
      binding induces receptor activation by neutralizing the inhibitory effect of this
      domain.

PMID- 9010218
TI  - Field cancerisation and polyclonal p53 mutation in the upper aero-digestive
      tract.
AB  - Field cancerisation of the aerodigestive tract is caused by chronic exposure to
      alcohol and tobacco, but the nature of the genetic alterations preceding overt
      malignancy is unknown. To identify potential field changes we have used a
      functional assay which tests the transcriptional competence of human p53
      expressed in yeast. To increase the sensitivity and reliability of the technique
      for samples containing under 20% mutant p53, the 5' and 3'-ends of the p53 cDNA
      were examined separately. With this split form of the assay the tissue p53 mRNA
      acts as its own control for RNA quality. Mutations were detected in 87% (46/53)
      of tumours, reflecting the high sensitivity of the technique. Multiple biopsies
      of histologically normal tissue from the upper aero-digestive tract were tested
      and clonal p53 mutations were identified in 76% (38/50) of biopsies from patients
      presenting with multiple tumours compared with 32% (38/117) of biopsies from
      patients presenting with single tumours (P<0.000001). All patients (16/16)
      presenting with multiple tumours had at least one positive biopsy, compared with
      only 53% (19/36) of patients presenting with single tumours (P <0.001). This
      defines expansion of multiple clones of mutant p53-containing cells as an
      important biological mechanism of field cancerisation, and provides a means to
      identify patients likely to benefit from intensive screening for the development
      of new head and neck tumours.

PMID- 9010219
TI  - Nuclear accumulation of FGF-2 is associated with proliferation of human
      astrocytes and glioma cells.
AB  - FGF-2 has been implicated in the neoplastic transformation of glioma cells and in
      the transition of normal quiescent astrocytes to a proliferating, reactive state.
      In the present study we have observed that in human glial cells, levels and
      subcellular localization of FGF-2 are different in quiescent and proliferating
      cells. FGF-2 was detected in the cytoplasm of non-reactive astrocytes in human
      brain sections. In contrast FGF-2 was located within the cytoplasm and nuclei of
      reactive astrocytes in gliotic brain tissue and in neoplastic cells of glioma
      tumors. In vitro, FGF-2 was found predominantly in the nucleus of subconfluent
      proliferating astrocytes, but was detected only in the cytoplasm of density
      arrested quiescent astrocytes. Our results suggest that reduced cell contact
      stimulates nuclear accumulation of FGF-2, accompanying mitotic activation of
      reactive human astrocytes. FGF-2 was constitutively localized to the nucleus of
      continuously proliferating glioma cells independent of cell density. A role for
      intracellular FGF-2 was further suggested by the observation that glioma cells
      that are not stimulated to proliferate by extracellular FGF-2 proliferated faster
      when transfected with FGF-2 expressing vectors. This increased proliferation
      correlated with nuclear accumulation of FGF-2. Cell proliferation was attenuated
      by 5'-deoxy-5'-methylthioadenosine, a FGF-2 receptor tyrosine kinase inhibitor
      that acts within the cell, but was unaffected by myo-inositol hexakis [dihydrogen
      phosphate] that disrupts FGF-2 binding to plasma membrane receptors. Our results
      indicate that FGF-2 serves as a nuclear regulator of proliferation in astrocytic
      cells. In glioma cells, the constitutive presence of FGF-2 in the nucleus may
      promote proliferation that is insensitive to cell contact inhibition.

PMID- 9010220
TI  - Identification of p53 genetic suppressor elements which confer resistance to
      cisplatin.
AB  - Loss of p53 function is associated with the acquisition of cisplatin resistance
      in the human ovarian adenocarcinoma A2780 cell line. Selection for cisplatin
      resistance of A2780 cells was used to isolate genetic suppressor elements (GSEs)
      from a retroviral library expressing random fragments of human or murine TP53
      cDNA. Six GSEs were identified, encoding either dominant negative mutant peptides
      or antisense RNA molecules which corresponded to various regions within the TP53
      gene. Both types of GSE induced cisplatin resistance when introduced individually
      into A2780 cells. Expression of antisense GSEs led to decreased intracellular
      levels of p53 protein. One sense GSE induced loss of p53-mediated activities such
      as DNA damage induced cell cycle arrest and apoptosis. A synthetic peptide,
      representing the predicted amino acid sequence of this GSE, conferred resistance
      to cisplatin when introduced into A2780 cells and inhibited the sequence specific
      DNA binding activity of p53 protein in vitro. Overall, these results directly
      indicate that inactivation of p53 function confers cisplatin resistance in these
      human ovarian tumour cells. We have identified short structural domains of p53
      which are capable of independent functional interactions and highlighted the
      efficacy of this approach to discriminate biologically active GSEs from a random
      fragment library.

PMID- 9010221
TI  - Cloning and characterization of AFX, the gene that fuses to MLL in acute
      leukemias with a t(X;11)(q13;q23).
AB  - We report the cloning and characterization of the entire AFX gene which fuses to
      MLL in acute leukemias with a t(X;ll)(q13;q23). AFX consists of two exons and
      encodes for a protein of 501 amino acids. We found that normal B- and T-cells
      contain similar levels of AFX mRNA and that both the MLL/AFX as well as the
      AFX/MLL fusion transcripts are present in the cell line and the ANLL sample with
      a t(X;11)(q13;q23). The single intron of the AFX gene consists of 3706
      nucleotides. It contains five simple sequence repeats with lengths of at least 12
      bps, a chi-like octamer sequence (GCA/TGGA/TGG) and several immunoglobulin
      heptamer-like sequences (GATAGTG) that are distributed throughout the entire AFX
      intron sequence. In the KARPAS 45 cell line the breakpoints occur at nucleotides
      2913/2914 of the AFX intron and at nucleotides 4900/4901 of the breakpoint
      cluster region of the MLL gene. The AFX protein belongs to the forkhead protein
      family. It is highly homologous to the human FKHR protein, the gene of which is
      disrupted by the t(2;13)(q35;q14), a chromosome rearrangement characteristic of
      alveolar rhabdomyosarcomas. It is noteworthy that the t(X;11)(q13;q23) in the
      KARPAS 45 cell line and in one acute nonlymphoblastic leukemia (ANLL) disrupts
      the forkhead domain of the AFX protein exactly at the same amino acids as does
      the t(2;13)(q35;q14) in case of the FKHR protein. In addition, the 5'-part of the
      AFX protein contains a conserved hexapeptide motif (QIYEWM) that is homologous to
      the functionally important conserved hexapeptide QIYPWM upstream of the homeobox
      domain in Hox proteins. This motif mediates the co-operative DNA binding of Pbx
      family members and Hox proteins and, therefore, plays an important role in
      physiologic and oncogenic processes. In acute leukemias with a t(X;11)(q13;q23),
      this hexapeptide motif is separated from the remaining forkhead domain within the
      AFX protein. The predicted amino acid sequence of AFX differs significantly from
      the partial AFX protein sequence published previously (Genes, Chromosomes and
      Cancer, 1994, 11, 79-84). This discrepancy can be explained by the occurrence of
      two sequencing errors in the earlier work at nucleotide number 783 and 844 (loss
      of a cytosine residue or guanosine residue, respectively) that lead to two
      reading frame shifts.

PMID- 9010222
TI  - Oncogenic activation of c-Myb by carboxyl-terminal truncation leads to decreased
      proteolysis by the ubiquitin-26S proteasome pathway.
AB  - c-myb activation by insertional mutagenesis in murine myeloid leukemias can lead
      to amino (NH2)-terminal or carboxyl (COOH)-terminal truncation of its protein
      product. We observed that in these leukemias, the steady state level of the
      protein truncated at the COOH terminus was remarkably higher than that of the
      protein truncated at the NH2-terminus or full length wild-type protein. To
      examine the rate of proteolysis of different forms of Myb in a uniform cellular
      background, the proteins were constitutively expressed in the myeloblast cell
      line M1, using the retrovirus vector LXSN. In pulse chase experiments, using
      metabolically 35S-labeled proteins, it was determined that COOH-terminal
      truncation of c-Myb by 248 aa (CT-c-Myb) substantially increases protein
      stability, resulting in a t1/2 of about 140 min, as compared to 50 min for full
      length c-Myb (FL-c-Myb). In an investigation of the mechanism involved in the in
      vivo degradation of this short lived transcription factor, inhibitors of the
      lysosomal (chloroquine), proteasomal (ALLM, ALLN, lactacystin) and calpains
      (EGTA, E-64d, BAPTA/AM) pathways were utilized. Results of this experiment
      identified the 26S proteasome as a major pathway responsible for rapid breakdown
      of the protein in hematopoietic cells. Further experiments carried out in vitro
      demonstrated that c-Myb can be ubiquitinated, suggesting that this process may be
      involved in the targeting of wild-type c-Myb to degradation by the 26S
      proteasome. In addition, it was demonstrated that CT-c-Myb was less efficiently
      ubiquitinated than wild-type protein indicating that defects in modification
      account for its escape from rapid turnover. We speculate that the increased half
      life of c-Myb resulting from truncation could contribute to its transforming
      potential.

PMID- 9010223
TI  - FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function
      as ternary and quaternary complex factors on the Egr1 promoter serum response
      elements.
AB  - The ETS gene products are a family of transcriptional regulatory proteins that
      contain a highly conserved and structurally unique DNA binding domain, termed the
      ETS domain. Several ETS proteins bind to DNA as monomers, however it has been
      shown that the DNA binding activity is enhanced or modulated in the presence of
      other factors. By differential display and whole genome PCR techniques, we have
      recently shown that the Erg1 gene is a target for ETS proteins. The Egr1 promoter
      contains multiple ETS binding sites, three of which exist as parts of two serum
      response elements (SREI and SREII). The SRE is a cis-element that regulates the
      expression of many growth factor responsive genes. ELK1 and SAP1a have been shown
      to form ternary complexes with SRF on the SRE located in the c-fos promoter.
      Similarly, we examined whether the ELK1, SAP1a, FLI1, EWS-FLI1, ETS1, ETS2, PEA3
      and PU.1 proteins can form ternary complexes with SRF on the Egr1 SREI and II.
      Our results demonstrate that indeed ELK1, SAPla, FLI1 and EWS-FLI1 are able to
      form ternary complexes with SRF on Egr1 SREs. In addition, ELK1 and SAP1a can
      also form quarternary complexes on the Egr1 SREI. However, the proteins ETS1,
      ETS2, PEA3 and PU.1 were unable to form ternary complexes with SRF on either the
      Egr1 or c-fos SREs. Our data demonstrate that FLI1 and EWS-FLI1 constitute new
      members of a subgroup of ETS proteins that can function as ternary complex
      factors and further implicate a novel function for these ETS transcription
      factors in the regulation of the Egr1 gene. By amino acid sequence comparison we
      found that, in fact, 50% of the amino acids present in the B-box of SAP1a and
      ELK1, which are required for interaction with SRF, are identical to those present
      in both FLI1 (amino acids 231- 248) and EWS-FLI1 proteins. This B-box is not
      present in ETS1, ETS2, PEA3 or PU.1 and these proteins were unable to form
      ternary complexes with SRF and Egrl-SREs or c-fos SRE. Furthermore, deletion of
      194 amino terminal amino acids of FLI1 did not interfere with its ability to
      interact with SRF, in fact, this truncation increased the stability of the
      ternary complex. The FLI1 protein has a unique R-domain located next to the DNA
      binding region. This R-domain may modulate the interaction with SRF, providing a
      mechanism that would be unique to FLI1 and EWS-FLI1, thus implicating a novel
      function for these ETS transcription factors in the regulation of the Egr1 gene.

PMID- 9010224
TI  - The Nck SH2/SH3 adaptor protein is present in the nucleus and associates with the
      nuclear protein SAM68.
AB  - SH2/SH3 adaptor proteins are essential components of the signal transduction
      pathways initiated by tyrosine kinases. Nck is a ubiquitously expressed adaptor
      protein whose function has been enigmatic. We performed confocal microscopy to
      localize Nck in NIH3T3 and A431 cells. Surprisingly, Nck was identified in the
      nucleus as well as the cytoplasm with no visible change in localization due to
      PDGF or EGF stimulation. Western blot analysis of nuclear and cytosolic fractions
      confirmed that there was no translocation in response to growth factor and that
      tyrosine phosphorylation was specific to only cytosolic Nck. Far Western blot
      analysis with either Nck, the SH2 domain, or the SH3 domains revealed
      differential binding in nuclear and cytosolic lysates, indicating specific
      binding partners for each subcellular location. The major target of c-Src during
      mitosis is SAM68, a RNA-binding protein ordinarily localized to the nucleus.
      SAM68 was identified as a nuclear specific binding partner of Nck in both
      nonmitotic and mitotic cells. Several tyrosine kinases can be found in the
      nucleus but their signal transduction remains undefined. The discovery of an
      adaptor protein in the nucleus suggests there are signal transduction mechanisms
      within the nucleus that recapitulate those found in the cytoplasm.

PMID- 9010225
TI  - Isolation and characterization of e3B1, an eps8 binding protein that regulates
      cell growth.
AB  - Eps8, a substrate of receptor tyrosine kinases, is an SH3 domain containing
      protein that plays an important role in mitogenic signaling. To determine the
      cellular function of eps8, we used the SH3 domain of eps8 to screen a human
      fibroblast M426 expression library and identified, a full-length cDNA clone of
      3.2 kb. We designated this clone e3B1 for eps8 SH3 domain binding protein 1.
      Northern analysis revealed that expression of e3B1 mRNA was ubiquitous in human
      tissues. The e3B1 gene encodes a SH3 domain containing protein. We show that anti
      e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in
      cell lysate isolated from asynchronously growing NIH3T3 cells. E3B1 binds to the
      SH3 domain of eps8 and Abl in vitro. We also demonstrated that e3B1 associates
      with eps8 in vivo. Phosphatase digestion and phosphoamino acid analysis revealed
      that p65e3B1 is a phosphoserine containing protein and p72e3B1 and p68e3B1 are
      hyperserine-phosphorylated form of p65e3B1. We further determined that the
      p65e3B1 was the most abundant in serum-starved NIH/EGFR cells. Time course
      studies initiated by the addition of epidermal growth factor (EGF) revealed that
      the p72e3B1 started to accumulate at 4 h, peaked at 8 h and remained high until
      24 h. Finally, we demonstrate that NIH/EGFR fibroblasts overexpressing e3B1 grow
      more slowly relative to matched controls.

PMID- 9010226
TI  - Cytotoxic activity of a diptheria toxin/FGF6 mitotoxin on human tumour cell
      lines.
AB  - The FGFs constitute a family of, at least, 12 polypeptides (FGF1 to FGF12)
      implicated in a number of physiological and pathological processes throughout
      embryogenesis and adult life. They bind to at least three types of cell surface
      molecules, including four high affinity transmembrane tyrosine kinase receptors
      (FGFR1 to FGFR4). In addition to important roles during development, FGF
      involvement in pathological conditions, including tumour formation, has been
      suspected, and overexpression of FGFR in tumour specimens is well documented.
      Diphtheria Toxin/FGF6 (DT/FGF6) mitotoxin has been shown to selectively and
      effectively target FGFR1-expressing cells. We show here that DT/FGF6 targets
      myoblasts engineered to express either one of the four FGFR, as well as FGFR
      expressing tumour cells.

PMID- 9010227
TI  - Monoclonal antibodies specific for underphosphorylated retinoblastoma protein
      identify a cell cycle regulated phosphorylation site targeted by CDKs.
AB  - The growth suppressive activity of the retinoblastoma tumour suppressor protein
      is controlled by cell cycle dependent phosphorylation. However, while many in
      vivo phosphorylation sites have been mapped, the identities of those residues
      whose phosphorylation is regulated remain elusive. We have mapped the epitopes of
      three independent monoclonal antibodies that recognise a distinction between
      differentially phosphorylated pRB sub-populations. All three antibodies recognise
      an identical epitope which encompasses an essential serine positioned within a
      consensus site for proline directed kinase phosphorylation. We provide evidence
      that this residue, serine 608 of pRB, is an authentic phosphorylation site that
      can be phosphorylated in vitro by cyclin A-CDK2 and cyclin D1-CDK4 kinases but
      not by cyclin E-CDK2 kinase or the mitogen activated kinase ERK2. Phosphorylation
      at this residue seems to be cell cycle regulated, occurring prior to entry into
      the S phase.

PMID- 9010229
TI  - The PDGF receptor phosphorylates Tyr 138 in the c-Src SH3 domain in vivo reducing
      peptide ligand binding.
AB  - Treatment of quiescent NIH3T3 cells with PDGF BB results in the transient
      activation and hyperphosphorylation of the protein-tyrosine kinase, c-Src. These
      effects correlate with novel serine and tyrosine phosphorylations in the N
      terminal non-catalytic region of the molecule, which contains an SH3 and SH2
      domain. In this study, a site of PDGF-induced tyrosine phosphorylation was mapped
      to Tyr 138 in the SH3 domain; Tyr 138 is exposed on the SH3 peptide binding
      surface. This same site is phosphorylated in vitro by the PDGF receptor when
      purified baculovirus-expressed c-Src is complexed with the activated receptor.
      Phosphorylation of Tyr 138 required association of c-Src with the PDGF receptor
      via its SH2 domain. When a c-Src Phe 138 mutant was stably expressed in Src-
      mouse fibroblasts, it was activated to the same extent as wild type c-Src
      following PDGF stimulation, indicating that phosphorylation of this site is not
      required for PDGF-mediated activation. However, Tyr 138 phosphorylation was found
      to diminish SH3 domain peptide ligand binding ability in vitro.

PMID- 9010228
TI  - Differential subcellular localization, expression and biological toxicity of
      BRCA1 and the splice variant BRCA1-delta11b.
AB  - The mechanism of BRCA1 tumor suppression in human breast and ovarian cells is the
      focus of intense investigation. In this report, full length BRCA1 (230 kDa)
      introduced into cells with CMV promoter constructs was nuclear when transgene
      expression was low whereas high expression resulted in cytoplasmic accumulation,
      aberrant nuclear and cell morphology. A nuclear localization signal (NLS) was
      mapped to BRCA1 amino acid positions 262-570. We describe a splice variant, BRCA1
      delta11b, missing the majority of exon 11 including the NLS. Exogenous BRCA1
      delta11b (110 kDa) was cytoplasmic and, unlike the full-length protein,
      overexpression of the protein encoded by the variant did not appear to be toxic.
      RNA probe titrations and RT-PCR demonstrated that BRCA1 and delta11b transcripts
      are coexpressed in a wide variety of cells and tissues. Interestingly, BRCA1
      delta11b message was greatly reduced or absent in several breast and ovarian
      tumor lines relative to exon 11 transcripts and a delta9,10 splice variant. Taken
      together our results suggest that full-length BRCA1 and BRCA1-delta11b may have
      distinct roles in cell growth regulation and tumorigenesis.

PMID- 9010230
TI  - Identification of Elf-1 and B61 as high affinity ligands for the receptor
      tyrosine kinase MDK1.
AB  - Mouse Developmental Kinase 1 (MDK1) is a receptor tyrosine kinase of the eck/eph
      subfamily expressed in a variety of tissues during early mouse embryogenesis. To
      obtain further insight into the function of MDK1, we determined identity and
      localisation of its physiological ligand(s). Staining whole embryos with fusion
      proteins between the extracellular domain of MDK1 and human secreted alkaline
      phosphatase revealed areas of high receptor binding in the caudal mesencephalon,
      the frontal neocortex and the limb buds. This staining was sensitive to treatment
      with phosphatidylinositol-specific phospholipase C. Using Scatchard analysis,
      high affinity binding of Elf-1 (1.7 x 10(-10) M) and B61 (2.2 x 10(-10) M)
      towards MDK1 could be demonstrated. However, the transmembrane ligand Lerk2
      displayed no measurable affinity for MDK1. Elf-1 and B61 bind to the three full
      length MDK1 isoforms with similar dissociation constants. Slightly lower
      affinities were observed for the two truncated receptors MDK1-Tl and MDK1-T2. The
      activation of MDK1 with Elf-1 or B61 leads to the rapid autophosphorylation of
      MDK1 as well as tyrosine phosphorylation of an unknown 62 kDa phosphoprotein in
      Rat1 cells. These findings implicate MDK1 in patterning processes during early
      mouse embryogenesis and suggest MDK1 involvement in early organogenesis and
      midbrain development.

PMID- 9010231
TI  - p21(WAF1/CIP1) response to genotoxic agents in wild-type TP53 expressing breast
      primary tumours.
AB  - Functional inactivation of the wild-type p53 protein has been described in
      different human cancers. Since a significant proportion of breast tumours express
      wild-type TP53, the p53 antiproliferative activity could be inactivated in
      transformed mammary epithelial cells by a mechanism independent on structural
      alteration of the gene. To test this hypothesis, we analysed the p53 activity in
      primary breast tumour cells. As a preliminary study, we demonstrated in breast
      adenocarcinoma cell lines that the nuclear accumulation of the inhibitor of
      cyclin dependent kinase p21(WAFl/CIP1), in response to adriamycin treatment,
      specifically reflected the activity of a functional wild-type p53 protein. Then,
      we used this strategy to study the p53 activity in 23 primary breast tumours.
      p21(WAF1/CIP1 accumulation was detected in all tumours expressing wild-type TP53.
      In contrast, no p21(WAF1/CIP1) response was detected in cells harboring a mutant
      TP53 gene. This report is the first functional study of p53 in primary breast
      tumours. The results demonstrate that TP53 mutation represents the only common
      mechanism leading to an irreversible inactivation of p53 functions in this cancer
      type.

PMID- 9010232
TI  - Differential cell cycle effects induced by E2F1 mutants.
AB  - Expression of two types of transactivation-defective E2F1 mutants in human Rb-/-
      tumor cells led to an increase in the proportion of cells in the G1 phase of the
      cell cycle as determined by FACS analysis. Experiments revealed two different
      mechanisms of action. One mutant type induced a G1 arrest after the restriction
      point, with cells phenotypically at a cell cycle stage later than G1. The action
      of this mutant was, at least in part, dependent on specific DNA binding and was
      over-ridden by co-expression of its wild-type counterpart. The other mutant type,
      which is defective in DNA binding, slowed the G1 progression and restored a
      checkpoint for cell cycle withdrawal. The G1 phase withdrawal of these tumor
      cells allowed the initiation of skeletal muscle cell differentiation. Thus, E2F1
      appears to have two different functions before and after the cell cycle
      restriction point. This report also may provide a basis for a gene therapy
      approach for certain human cancers.

PMID- 9010233
TI  - Transcriptional down-regulation of myogenin expression is associated with v-ras
      induced block of differentiation in unestablished quail muscle cells.
AB  - Unestablished quail myoblasts were infected with a retroviral vector encoding the
      oncogenic form of H-Ras in order to investigate the mechanism by which this
      oncoprotein interferes with terminal differentiation. Primary quail myogenic
      cells exhibit the simultaneous expression of the muscle regulatory genes myf-5,
      MyoD and myogenin in proliferative conditions. v-ras-transformed myoblasts
      displayed an altered growth control and lost the competence for terminal
      differentiation. When expression of myogenic regulatory genes was analysed, it
      was immediately apparent that the difference between normal and v-ras-transformed
      cells was limited to a severely decreased level of myogenin expression. Forced
      expression of exogenous myogenin in v-ras-transformed quail myoblasts led to a
      striking recovery of the competence for terminal differentiation. The present
      data show that: (i) repression of myogenin expression is linked to the
      differentiation defective phenotype of quail myoblasts transformed by v-ras as
      well as other retroviral oncogenes; (ii) correction of the differentiation
      defective phenotype of v-ras-transformed myoblasts by exogenous myogenin entailed
      reactivation of endogenous myogenin and of the E-box-dependent transactivating
      function. These results strongly indicate that myogenin expression plays a
      central role in regulating the transition into the terminally differentiated
      state and that its transcriptional down-regulation represents a nodal step in v
      ras-induced block of differentiation.

PMID- 9010234
TI  - Heterodimerization of Hox proteins with Pbx1 and oncoprotein E2a-Pbx1 generates
      unique DNA-binding specifities at nucleotides predicted to contact the N-terminal
      arm of the Hox homeodomain--demonstration of Hox-dependent targeting of E2a-Pbx1
      in vivo.
AB  - Hox proteins control genetic programs that orchestrate development, and a large
      subset of Hox proteins can bind DNA elements as heterodimers with the Pbx family
      of homeodomain proteins. A transcriptionally activated version of Pbx1, E2a-Pbx1,
      is an oncoprotein in human pre-B cell leukemia that strongly suppresses
      differentiation and retains its ability to heterodimerize with Hox proteins.
      Because monomeric Hox proteins bind very similar DNA motifs, it is unclear how
      they activate diverse developmental programs. Here we demonstrate that
      heterodimers containing different Hox proteins and a common Pbx1 or E2a-Pbx1
      partner bind different DNA motifs. Structural models suggest that the specificity
      of the Hox protein is altered by a conformation change involving residues in the
      N-terminal arm of the Hox homeodomain. Mutational analysis also supported the
      hypothesis that unique sequences in the N-terminal arm of the Hox homeodomain are
      at least partially responsible for mediating this specificity. In vivo, Hox
      proteins directed E2a-Pbx1-mediated transactivation with moderate specificity to
      cognate Hox-Pbx motifs. Thus, the development specificity of individual Hox
      proteins may be mediated, in part, by differential targeting of cellular genes by
      Pbx1-Hox complexes. Likewise, through its function as a common heterodimer
      partner, oncoprotein E2a-Pbx1 may be able to interfere with multiple programs of
      development that are induced by the sequential or simultaneous expression of Hox
      proteins during hematopoiesis.

PMID- 9010235
TI  - Further characterisation of the p53 responsive element--identification of new
      candidate genes for trans-activation by p53.
AB  - The p53 protein is known to trans-activate a number of genes by specific binding
      to a consensus sequence containing two decamers of the type:
      PuPuPuCA/TT/AGPyPyPy. In order to identify new p53 trans-activated genes, we
      defined a set of criteria for computer search of p53-responsive elements. Based
      on experimental data, we proposed an extended consensus sequence composed of the
      two decamers of the El-Deiry consensus sequence flanked by two additional ones. A
      maximum of 3 bp substitutions was accepted for the two decamers of the El-Deiry
      consensus sequence, as well as for each additional decamer, except when the two
      decamers of the El-Deiry consensus sequence are contiguous. In this case, each
      additional decamer is allowed to bear one base insertion or deletion between the
      median C and G. This set of criteria was validated by identifying within the
      promoter region of the IGF-BP3 gene the existence of a novel p53-responsive
      element whose functional significance was verified. By limiting our computer
      search to Vertebrate genes involved in cell cycle regulation, cellular adhesion
      or metastatic processes and to gene families most often found in HOVERGEN
      database, 7785 gene sequences were first analysed. Among the oncogenes, kinases,
      proteases and structural proteins, 55 new genes were selected; six of them were
      retrieved in more than one species.

PMID- 9010236
TI  - Unique expression patterns of H19 in human testicular cancers of different
      etiology.
AB  - The expression pattern of the imprinted human H19 gene was investigated in
      testicular cancers of different etiology, as well as in normal testicular
      parenchyma, parenchyma without germ cells, and adjacent to testicular germ cell
      tumors of adolescents and adults (TGCTs), using RNase protection analysis, mRNA
      in situ hybridization and reverse-transcription polymerase chain reaction. While
      different total expression levels were detected in spermatocytic seminomas,
      lymphomas, a Sertoli cell tumor and Leydig cell tumors, none showed a disturbance
      of monoallelic expression. Strikingly, the majority of invasive TGCTs revealed
      expression of both parental alleles. The total level of expression highly
      correlated with differentiation lineage and stage of maturation, similar to that
      as reported during early normal embryogenesis. Biallelic expression could also be
      determined specifically in testis parenchyma containing the preinvasive lesion of
      this cancer. We therefore conclude that within the adult testis, biallelic H19
      expression is specific for TGCTs, and that the level of expression is dependent
      on differentiation lineage and maturation stage. This is in agreement with the
      proposed primordial germ cell-origin of this cancer, and might be related to
      retention of embryonic characteristics in TGCTs. In addition, our data argue
      against H19 being a tumor suppressor gene.

PMID- 9010237
TI  - Loss of heterozygosity on murine chromosome 6 in two-stage carcinogenesis:
      evidence for a conserved tumor suppressor gene.
AB  - We have recently demonstrated that loss of heterozygosity (LOH) at 7q31 is
      frequent in many kinds of human primary tumors and that introducing a single
      human chromosome (hchr) 7 into a murine squamous cell carcinoma (SCC)-derived
      cell line suppresses the malignant phenotype. To investigate whether the putative
      tumor suppressor gene on hchr 7 is conserved in mice, we studied LOH on mouse
      chromosome (mchr) 6 in chemically induced SCCs in (C57BL x DBA2) F1 (B6D2F1)
      females. LOH analysis was performed by polymerase chain reaction amplification of
      17 (CA)n microsatellite repeats in mchr 6 A1-C3. As expected, all the B6D2F1
      derived tumors were informative for all the locus assayed. The highest percentage
      of LOH in the hchr 7q-homologous segment was found at D6Mit50 (60.0%) and the
      other markers in this segment had LOH incidences normally distributed around the
      peak. The high incidence of LOH in the tumors studied suggests that a tumor
      suppressor gene relevant to the development of epithelial cancers is present on
      mchr 6 A2. As this segment is homologous with hchr 7q31, these data suggest that
      the putative tumor suppressor gene is conserved in the two species and explains
      the suppression of tumorigenicity when a single hchr 7 is introduced to a murine
      SCC cell line.

PMID- 9010238
TI  - BRCA1 expression is not directly responsive to estrogen.
AB  - Expression of the breast cancer susceptibility gene, BRCA1, is induced by 17-beta
      estradiol (E2) in estrogen receptor containing breast cancer cell lines. Our
      previous studies have shown that BRCA1 transcription is also regulated with the
      cell cycle, reaching maximal levels just before the onset of DNA synthesis. In
      this study, we have examined whether the estrogen induction of BRCA1 is direct or
      is a result of the mitogenic activity of the hormone. Four lines of evidence lead
      us to conclude that E2 induces BRCA1 primarily through an increase in DNA
      synthesis: (1) The kinetics and magnitude of induction are different from the
      directly E2 inducible gene, pS2; (2) Induction of BRCA1, but not pS2, is blocked
      by cycloheximide indicating that de novo protein synthesis is required; (3) Other
      hormonal and growth factor treatments that induce DNA synthesis have a similar
      effect, including IGF-1, EGF and DNA synthetic flares induced by tamoxifen and
      retinoic acid; (4) BRCA1 genomic fragments near the 5' end of the gene containing
      putative estrogen response elements fail to respond to E2 when transfected into
      breast cancer cell lines. The most consistent explanation for these findings and
      other published studies is that BRCA1 transcription is induced as a result of the
      mitogenic activity of E2 in estrogen receptor positive cells.

PMID- 9010239
TI  - Deregulated expression of the PU.1 transcription factor blocks murine
      erythroleukemia cell terminal differentiation.
AB  - Murine erythroleukemia (MEL) cells are transformed erythroid precursors that are
      blocked from completing the late stages of erythroid differentiation. A frequent
      event in the generation of these malignant cells is deregulation of the
      hematopoietic-specific transcription factor PU.1 (Spi-1) by retroviral insertion
      of the spleen-focus-forming virus component of Friend virus. During chemically
      induced reinitiation of MEL cell terminal differentiation, expression of PU.1 is
      rapidly down-regulated, suggesting that PU.1 might interfere with processes
      required for terminal differentiation of erythroid precursors. To investigate the
      role of PU.1 in erythroid differentiation we transfected MEL cells with a PU.1
      cDNA controlled by the eucaryotic translation elongation factor EF1 alpha
      promoter. Deregulated expression of PU.1 blocked chemically induced
      differentiation and terminal cell division. Deregulated expression of two other
      protooncogenes, c-myc and c-myb, also has been shown to block MEL
      differentiation. We present evidence that PU.1 inhibits terminal differentiation
      at an earlier step than c-Myc and c-Myb. Thus reinitiation of MEL cell terminal
      differentiation appears to be controlled by an ordered program of turning off
      several protooncogenes. Down-regulation of PU.1 may be a very early step in this
      program.

PMID- 9010240
TI  - Recombinant fusion peptides containing single or multiple repeats of a ubiquitous
      T-helper epitope are highly immunogenic.
AB  - Two recombinant mouse mammary tumor virus (MMTV) subunit vaccines have been
      constructed, in which linear sequences of the envelope gp 52 glycoprotein (EP3)
      or the superantigen (SAg) have been fused to single or multiple repeats of a T
      cell epitope (P30) from tetanus toxin. Histidine tags or glutathione-S
      transferase (GST) sequences have been included in the recombinant peptides in
      order to facilitate their purification by affinity chromatography. The EP3 or SAg
      recombinant polypeptides with four, one, or no T-cell epitopes were expressed in
      Escherichia coli, purified and injected intramuscularly, with non-ionic block
      copolymers as an adjuvant, into BALB/c mice. Following one or two boosts, the B-
      and T-cell responses against the recombinant proteins were analysed. The addition
      of T-cell epitopes considerably increased the immunogenicity of the subunit
      vaccines. The anti-EP3 response was maximum with four T-cell epitopes, while a
      single T epitope was optimal for the anti-SAg response.

PMID- 9010241
TI  - Transforming growth factor-beta2-mediated regulation of C3 gene expression in
      monocytes.
AB  - In this report, we show that transforming growth factor-beta2 (TGF-beta2)
      regulates C3 gene expression in the human monocyte cell lines, U937 and THP-1,
      and human peripheral blood monocytes. Treatment of U937 or THP-1 cells with TGF
      beta2 resulted in a dose-dependent induction of C3 protein and mRNA expression.
      Dose-dependent increases of C3 protein and mRNA levels were also detected in TGF
      beta2-treated primary blood monocytes, demonstrating that TGF-beta2 can modulate
      C3 expression in nontransformed monocytes. Kinetic analysis demonstrated that TGF
      beta2-mediated induction of C3 mRNA and protein could be detected within 8 hr,
      and the induction was continuous up to 72 hr. Exposure of cells to TGF-beta2 for
      as little as 2 hr was sufficient to induce C3 expression. TGF-beta2 did not
      significantly increase C3 mRNA stability as determined by mRNA half-life studies.
      Collectively, our results demonstrate that TGF-beta2 regulates the expression of
      C3 in monocytes and suggest that TGF-beta2 may play a role in modulating the
      synthesis of C3 during inflammatory responses.

PMID- 9010242
TI  - High incidence of a T nucleotide at the second position of codon 97 in Vdelta2
      (D)-Jdelta1 junctional sequences of human normal skin gamma delta T-cells.
AB  - In this investigation, we have demonstrated that in-frame polyclonal Vdelta2-(D)
      Jdelta1 junctional sequences from human skin gammadelta T-cells contain a high
      incidence of T nucleotides at the second position of codon 97. Analysis of the
      deduced amino acid sequences based on in-frame Vdelta2-(D)-Jdelta1 junctional
      nucleotide sequences from normal skin gammadelta T-cells revealed a high
      incidence of the amino acids valine and leucine at position 97. These results are
      consistent with the studies in peripheral blood gammadelta T-cells, but not with
      previous findings in skin gammadelta T-cells, where random nucleotides were
      observed in the second position of codon 97 of Vdelta2-(D)-Jdelta1 junctional
      sequences and only a small minority of the deduced Vdelta2-(D)-Jdelta 1 amino
      acid sequences showed the amino acids valine and leucine at codon 97. Therefore,
      our findings indicate that the human skin gamma delta T-cells with a T-cell
      receptor consisting of a Vdelta2-(D)-Jdelta1-C delta1 chain are not a subset
      distinct from the subpopulation of human peripheral blood gammadelta T-cells
      expressing the same chain.

PMID- 9010243
TI  - Sequence comparisons of the CDR3 hyper-variable loops of human T cell receptors
      specific for three major T cell epitopes of the birch pollen allergen Bet v 1.
AB  - We have analysed the T cell receptor (TCR) alpha and beta chain sequences of 16
      human CD4+ T cell clones (TCCs) specific for three important epitopes of the
      major birch pollen allergen Bet v 1. The TCCs were raised from the peripheral
      blood of eight patients with birch pollen allergy, showing allergic rhino
      conjunctivitis and allergic asthma. The TCCs from these individuals were specific
      for Bet v 1-derived peptides: amino acids (aa)77-92 (epitope 1), aa93-108
      (epitope 2) and aa113-126 (epitope 3). The DNA sequence analysis of the TCRAV and
      BV regions revealed heterogeneous repertoires for recognition of the peptides.
      Multiple combinations of AV/AJ and BV/BJ were used. However, some inter
      individual restriction was evident. A limited selection of AVS and the normally
      infrequently used BV1S4 was obvious in TCCs specific for epitope 1. The TCRBV13
      was more frequent in TCCs recognizing epitope 3. A very narrow distribution in
      length could be seen in the CDR3 sequences of the beta chain of TCRs with
      specificity for epitopes 1 and 2. Inter-individual positional micro-restriction
      was observed for the aa motif LR in the tCDR3 (epitope 1), for the aa residue M
      in the alphaCDR3 and for the aa residue G in the betaCDR3 (epitope 3). Our
      results illustrate clearly that each antigenic peptide derived from a single
      allergen, is capable of selecting different characteristics in the responding
      repertoire of TCRs, thus increasing the complexity of allergen-recognition by T
      lymphocytes. Therefore, our findings limit the potential use of TCR targeted
      therapeutical strategies in Type I allergy.

PMID- 9010244
TI  - Human recombinant antibody fragments specific for a rye-grass pollen allergen:
      characterization and potential applications.
AB  - One of the major allergens from the pollen of perennial rye grass (Lolium
      perenne), Lol pII, was used to isolate specific antibody fragments from a random
      combinatorial library displaying a large repertoire of human Fab on filamentous
      phages. After five panning cycles on recombinant Lol pII immunotubes, phage
      binders were isolated and the antibody fragments expressed as soluble Fab
      molecules in the Escherichia coli periplasm. The DNA sequencing of the clones
      producing antibodies with the highest binding activity showed three of them to be
      identical, while one differed by two amino acid substitutions in the heavy chain.
      The antibody fragments were produced in milligram amounts, affinity-purified and
      further characterized. They bound the natural allergen as well as the recombinant
      one, with no cross-reactivity with other allergens contained in the pollen
      extract of L. perenne. One antibody bound the allergen with Kd = 2.63 x 10(-9) M,
      as demonstrated by the surface plasmon resonance technique, and was able to
      compete with a fraction of serum IgE. Epitope mapping using synthetic peptides
      revealed that antigenic domains, located between amino acids 39 and 51 of Lol
      pII, are recognized by Fab and polyclonal IgE from sera of allergic donors. The
      Fab fragments inhibited the binding of serum IgE to the allergen. In vitro
      experiments on whole blood from allergic subjects showed that recombinant Fab
      fragments had a blocking activity on histamine release from cells challenged with
      recombinant Lol pII allergen. Thus, serum IgE and recombinant Fab fragments
      recognize common epitopes, although they represent the outcome of different
      maturation and/or selection processes. Our molecular and functional findings
      altogether indicate that allergen-specific human antibodies may be useful for the
      characterization of the antigenic structure of allergens. We conclude that a
      phage library is a powerful source of anti-allergen human antibodies with high
      affinity and high specificity. Moreover, these molecules may be potentially
      innovative reagents for the treatment of atopic allergy.

PMID- 9010245
TI  - Isolation and characterization of a TATA-less promoter for the human RAG-1 gene.
AB  - Human recombination activating gene-1 (RAG-1) genomic DNA clones containing the
      first exon coding for the 5' untranslated region and the second exon coding for
      the remaining 5' untranslated region, coding region, and 3' untranslated region
      were cloned. Primer extension analysis and RNase protection analysis demonstrated
      the multiple RAG-1 transcription start sites, clustered in a 31 nucleotide (nt)
      region. Sequence analysis showed that the RAG-1 promoter lacked a TATA box as
      well as an initiator sequence. Transient expression assays using a luciferase
      reporter gene with truncated promoter fragments and substitution mutants, showed
      that the 5' promoter region containing the CCAAT box between -110 and -86, is
      indispensable for its basal promoter activity in RAG-1 expressing Nalm 6 cell
      line. Comparative transient expression assays in various cell lines revealed that
      the 854 nt upstream promoter region was active, not only in RAG-1 expressing cell
      lines but also in RAG-1 non-expressing cell lines. These data indicate that the
      854 nt upstream region of RAG-1 gene confer basal promoter activity, and that the
      tissue- and stage-specific expression of RAG-1 is controlled by elements present
      outside of the promoter region and/or differential chromatin structure(s) of the
      individual cells.

PMID- 9010246
TI  - Effects of secondary forces on the ligand binding properties and variable domain
      conformations of a monoclonal anti-fluorescyl antibody.
AB  - Biochemical interactions occurring external to the antibody active site or pocket
      (i.e. secondary forces) that directly effect ligand binding efficiency, and the
      microenvironment-sensitive spectral properties of bound homologous ligand,
      residing within the active site of high affinity monoclonal antifluorescyl
      antibody (mAb) 4-4-20, have been previously reported. This study describes the
      synthesis and characterization of a series of specially designed and chemically
      distinct mono-fluoresceinated peptides of equal size (13-mer) as well as the
      changes in the spectral properties and free energy in the binding of each
      fluorescein derivatized peptide, upon interaction with mAb 4-4-20. Significant
      differences in binding efficiency and fluorescence quenching of the ligand, as
      well as the intrinsic tryptophan fluorescence, were observed for each
      monofluoresceinated peptide relative to one another and fluorescein ligand. In
      addition to the effects on the fluorescence quenching of fluorescein and
      intrinsic tryptophan residues, and the free energy of binding, the conformation
      of the variable domains of mAb 4-4-20 upon interaction with the fluoresceinated
      peptides was probed with polyclonal antimetatype (conformational dependent anti
      liganded state) antibodies. Studies comparing the results of a solid-phase
      inhibition assay, with the binding of antimetatype antibodies in solution,
      suggested that variant metatypic states of mAb 4-4-20 resulted from binding of
      the various fluorescein derivatized peptides. Depiction of the mAb 4-4-20 active
      site as a series of thermally averaged substates is proposed as a model and
      framework to interpret further the results. It was concluded that secondary
      forces can dictate conformer selection from the various substates. thereby
      modulating the primary antibody ligand interaction.

PMID- 9010247
TI  - Role of muIP-10 in interferon-gamma induction of Ia in rat astrocytes.
AB  - Interferon-gamma, (IFNgamma) is a potent inducer of class II MHC (Ia) in rat
      astrocytes and microglia which are immunocompetent cells of the central nervous
      system (CNS). muIP-10, a member of the alpha-chemokine family, is also induced by
      IFNgamma in these cells. The induction of muIP-10 mRNA occurred in an immediate
      early manner, while Ia mRNA-induction was delayed and required new protein
      synthesis. We studied the possible role of muIP-10 in IFNgamma-mediated induction
      of Ia in astrocytes. Antibodies to muIP-10 protein significantly inhibited the
      expression of surface Ia molecules by astrocytes. Incubation of astrocytes with
      antisense-oligonucleotides against muIP-10 mRNA also reduced the number of Ia
      positive cells inducible by IFNgamma. Neither the number of IFNgamma-inducible
      class I MHC positive cells nor the number of class I molecules expressed per cell
      were affected by antisense-oligonucleotides against muIP-10, indicating the
      specificity of the oligonucleotide and the selective requirement of muIP-10 for
      Ia induction by IFNgamma. Transient transfection of astrocytes with plasmids
      expressing muIP-10 in the antisense orientation also reduced the number of Ia
      positive astrocytes. These studies suggest a role for muIP-10 protein as an
      autocrine factor that enhances the expression of IFNgamma-inducible Ia on
      astrocytes. This could create focal areas rich in Ia expressing cells which could
      more efficiently present antigens to T cells, leading to immune-mediated
      inflammation such as in multiple sclerosis.

PMID- 9010249
TI  - Poststreptococcal glomerulonephritis: getting to know an old enemy.

PMID- 9010248
TI  - Extrahepatic complement biosynthesis: where, when and why?

PMID- 9010250
TI  - Tuberculosis and immunodeficiency--of mice and men.

PMID- 9010251
TI  - Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo.
AB  - This study was performed to analyse correlates of viral escape in AIDS patients.
      Peripheral blood mononuclear cells (PBMC) from HIV- donors were inoculated with
      AIDS patients' serum to detect neutralization-resistant cell-free virus.
      Infectious virus was detected by polymerase chain reaction (PCR) and analysed by
      sequencing the V3 region. The escaped virus species was compared with all V3
      virus variants found in the patients' PBMC and plasma. In one patient escaped
      virus was also compared with variants found in CD4+ T cells isolated by FACS from
      blood, spleen and lymph node. The frequency of the virus variants was determined
      by cloning and sequence analysis of 20 V3 clones for each PCR amplification. To
      monitor anti-V3 antibodies by ELISA, each V3 sequence was expressed as fusion
      with glutathione S-transferase (GST-V3). In our AIDS patients, a V3-directed
      antibody response against the infectious virus V3 loop was not detectable. In
      contrast, virus variants unable to infect the donor PBMC in vitro were well
      recognized by homologous V3-directed antibody. After an interval of 1 year the
      frequency of these variants clearly decreased, while at the same time the escaped
      variants grew out and finally represented the predominant viral species both in
      plasma and PBMC. The infectious variants lacking V3 antibody response were also
      predominant in CD4+ T cells in spleen and lymph node. Our data indicate that the
      escape of virus variants is closely related to the lack of V3-directed antibody.

PMID- 9010252
TI  - T cell receptor (TCR) BV gene repertoires and clonal expansions of CD4 cells in
      patients with HIV infections.
AB  - Despite extensive investigation, the pathogenesis of T cell depletions that
      characterize AIDS has not been elucidated. To study this process further, we
      evaluated T cell antigen receptor beta-chain variable gene (TCRBV) repertoires in
      peripheral blood lymphocytes (PBL) of 23 HIV-infected patients. Expression levels
      of 28 TCRBV were determined by multiprobe RNase protection assay after polymerase
      chain reaction (PCR) amplifications. Abnormal expansions (> 2 s.d. from mean
      normal values) were frequent in HIV CD4, accounting for 26% of total measured
      TCRBV in this population. The number and magnitude of abnormalities among
      individuals were inversely proportional to their CD4 counts (P < 0.012 and P <
      0.01, respectively). While abnormalities were not randomly distributed among
      TCRBV subfamilies, no particular genes were expanded or contracted among all
      patients. Only 14% of CD8 TCRBV were proportionally expanded (P < 0.01 compared
      with CD4), and there were limited concordances between paired CD8 and CD4
      repertoires among individuals. CDR3 length analyses and TCRBV sequencing showed
      that most CD4 expansions comprised clonal or oligoclonal populations. Thus, T
      cell responses in HIV patients are characterized by severe TCRBV biases and
      clonal expansions among CD4 subsets, and these processes are exaggerated with
      disease progression. The heterogeneity and oligoclonality of the TCRBV expansions
      are consistent with responses to HIV-encoded or other conventional antigens
      rather than superantigenic effects. The presence of CD4 clonal proliferations in
      these patients may be important in the pathogenesis of HIV, and the absence or
      reduction of many T cell specificities due to oligoclonal expansions may increase
      susceptibility to opportunistic infections.

PMID- 9010253
TI  - Progression of HIV disease is associated with increased expression of Fc gammaRI
      and CR1 on alveolar macrophages.
AB  - The expression of receptors for complement and the Fc region of immunoglobulin by
      alveolar macrophages (AM) constitutes a valuable aid to effector function of
      these cells. However, during HIV infection such expression may also act to
      increase binding of immune complexes, thus facilitating viral infection of these
      cells. This study was designed to determine whether changes in the expression of
      these receptors occurs in situ during HIV infection. Lung macrophages were
      isolated by bronchoalveolar lavage in groups of HIV+ subjects segregated on the
      basis of peripheral CD4 count. A group of normal subjects was also investigated.
      Expression of CR1 and Fc gammaRI was quantified by measuring the optical density
      of reaction product following controlled immunoperoxidase staining with MoAbs
      CD35 and CD64. Both CR1 and Fc gammaRI were increased over normal in all HIV+
      subjects. This increase was progressive with advancing disease as determined by
      correlation with declining peripheral CD4 count. Comparison of asymptomatic and
      symptomatic subjects with HIV infection showed no difference in CR1 expression
      but a rise in Fc gammaRI expression in the latter group. An overall inverse
      correlation was also found between peripheral CD4 count and Fc gammaRI
      expression, but not CR1 expression. These data demonstrate a significant increase
      in the expression of these receptors on AM from HIV+ subjects, and show that this
      increase may occur before any symptoms in these patients.

PMID- 9010254
TI  - Febrile infection changes the expression of IgG Fc receptors and complement
      receptors in human neutrophils in vivo.
AB  - We have examined the expression of the IgG Fc receptors (FcRI, FcRII, FcRIII) and
      complement receptors (CR1, CR3) in neutrophils from 42 patients with febrile
      bacterial infection, 20 patients with febrile viral infection and 69 non-febrile
      healthy individuals. Using receptor-specific MoAbs and immunofluorescence flow
      cytometry the relative fluorescence intensity (as a measure of receptor number)
      and the proportion of receptor-positive cells were determined in peripheral blood
      neutrophils exposed to minimal processing, consisting only of erythrolysis. Both
      the percentage of FcRI-positive neutrophils and FcRI number per neutrophil were
      significantly (P < 0.001 and P < 0.0001) increased in bacterial infected patients
      compared with controls, whereas in viral infected patients only the FcRI
      percentage was markedly elevated (P < 0.05). In addition, both FcRII and CR1
      levels were significantly higher in the bacterial infection group than in the
      viral infection and control groups (bacterial versus control P < 0.001, bacterial
      versus viral P < 0.0001). No changes in expression of FcRIII or CR3 were found in
      the patient groups. The kinetic analysis of receptor expression in bacterial
      infection patients revealed a shift in the percentage of FcRI-bearing neutrophils
      towards normal values already on day 2 after the first analysis. On the other
      hand, the levels of FcRI, FcRII and CR1 remained clearly elevated in these
      patients during 1 week's follow-up period. We conclude that febrile infection may
      cause systemic activation of the entire pool of circulating neutrophils,
      resulting in alterations in cell surface receptor expression, some of which are
      characteristic of the nature of the infectious agent.

PMID- 9010255
TI  - Synthetic peptides based on Chlamydia trachomatis antigens identify cytotoxic T
      lymphocyte responses in subjects from a trachoma-endemic population.
AB  - CD8+ cytotoxic T lymphocytes (CTL) recognize peptide antigens in the context of
      class I MHC antigen molecules. To identify peptides capable of eliciting anti
      Chlamydia trachomatis CTL responses, 13 synthetic peptides conforming to human
      leucocyte antigen (HLA)-B8- or -B35-predicted binding motifs were synthesized
      using sequences based on C. trachomatis major outer membrane protein (MOMP) and
      heat shock protein 60 (hsp60). Two of 11 HLA-B35-predicted binding peptides were
      able to stabilize HLA-B35 in an in vitro binding assay. All peptides were tested
      in CTL assays using peripheral blood mononuclear cells (PBMC) isolated from 26
      HLA-B8 or -B35 individuals resident in a trachoma-endemic community. Responses to
      MOMP and hsp60 peptides were identified in a minority of both HLA-B8 and -B35
      individuals. Two of 12 HLA-B8 subjects responded to MOMP and 1/13 to hsp60
      peptides. Responses in HLA-B35 subjects were similar, 1/13 subjects responding to
      MOMP and 2/13 to hsp60 peptides. CTL responses were observed only in children
      resolving current infection and in adults without scarring of the conjunctiva.
      These results suggest that anti-chlamydial CTL occur at low levels in peripheral
      blood, but may be important in the resolution of naturally acquired human ocular
      chlamydial infection.

PMID- 9010256
TI  - Modulation of lymphocyte and monocyte activity after intravenous immunoglobulin
      administration in vivo.
AB  - In 12 patients with primary hypogammaglobulinaemia we investigated the in vivo
      effect of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on
      lymphocyte subsets and monocytes in peripheral blood, on plasma levels of soluble
      factors reflecting monocyte and lymphocyte activity and on lymphocyte
      proliferation and generation of reactive oxygen species (ROS) from monocytes
      analysed in vitro. Several immunological changes were induced by IVIG infusion.
      First, there was a significant decrease in CD4+/CD8+ lymphocyte ratio in
      peripheral blood, reflecting a significant increase in circulating numbers of
      CD8+ lymphocytes. Second, although there was no significant change in plasma
      levels of soluble CD8 antigen, there was a significant decrease in soluble CD8
      antigen/CD8+ lymphocyte ratio, suggesting a down-regulation of CD8+ lymphocyte
      activity. Third, there was a significant increase in plasma levels of neopterin,
      suggesting in vivo activation of monocytes/macrophages. Fourth, the was a down
      modulation of mitogen-stimulated lymphocyte proliferation in vitro, and this down
      regulation was significantly correlated with the increase in plasma neopterin
      levels. Finally, there was a significant decrease in zymosan-stimulated, but not
      in phorbol myristate acetate-stimulated, ROS generation from monocytes as
      evaluated by nitroblue tetrazolium reduction. The ability of IVIG administration
      in vivo to down-modulate lymphocyte proliferation and ROS generation from
      monocytes in patients with persistent immune activation may be relevant for the
      clinical effects of IVIG in a variety of immune-mediated disorders.

PMID- 9010257
TI  - The effects of vitamin A derivatives on in vitro antibody production by
      peripheral blood mononuclear cells (PBMC) from normal blood donors and patients
      with common variable immunodeficiency (CVID).
AB  - The underlying nature of the defect of CVID is not understood, and the treatment
      at present is life-long infusion of replacement immunoglobulin. Attempts have
      been made to use other therapeutic agents, such as IL-2 and retinoic acid (RA),
      with mixed results. RA is a morphogenetic signalling molecule related to vitamin
      A and involved in vertebrate development. We report here our in vitro evaluation
      of the effects of three vitamin A analogues, 9-cis retinal, 13-cis RA and all
      trans RA, on antibody production of PBMC from normal donors and patients with
      CVID. At 10(-5) M, 9-cis retinal strongly augmented IgM production of lymphocytes
      from normal individuals and to a much lesser extent, mild, non-granulomatous
      (group C) CVID patients, but IgG production was not affected. In the presence of
      anti-human IgM and IL-2, 9-cis retinal at 10(-5) M elevated IgM and IgG
      production by normal PBMC, but the effect on PBMC of mild CVID was minimal. The
      effect of 9-cis retinal was significantly reduced at 10(-7) and 10(-9) M. Only
      minimal effects were found using 13-cis RA and all-trans RA under these
      conditions. No detectable antibody production was found in severe, granulomatous
      (group A) CVID patients under any conditions tested. Taking all data into
      account, 9-cis retinal is the most potent stimulator for antibody production
      compared with 13-cis RA and all-trans RA as tested in this in vitro study.

PMID- 9010258
TI  - Experimental acute glomerulonephritis induced in the rabbit with a specific
      streptococcal antigen.
AB  - FITC-labelled IgG obtained from patients convalescing from acute
      poststreptococcal glomerulonephritis (APSGN) stains glomeruli of patients with
      early APSGN. We previously reported a streptococcal antigen (preabsorbing antigen
      (PA-Ag)) that preabsorbed the stain out of sera from the convalescent patients
      and thus prevented glomerular staining. To confirm the nephritogenicity of PA-Ag,
      we administered up to 40 mg of this antigen to rabbits for 8 days and observed
      them for up to 9 weeks. Immunohistological analysis showed diffuse and global
      glomerular staining for C3 without notable staining for gamma-globulin. Light
      microscopic examinations revealed slight to moderate proliferative
      glomerulonephritis with exudative change. Control rabbits, which received similar
      doses of bovine serum albumin, did not show significant staining for C3. A
      transient and significant decrease in CH50 was observed from weeks 3 to 7 (9.7 +/
      0.3 U/ml at week 3; normal range 12.9 +/- 0.6 U/ml). This experimental model
      showed a resemblance to immunological and immunohistological features of APSGN in
      humans. Although the precise mechanisms are yet to be determined, complement
      activation by PA-Ag seems to hold a key position in this model and in the human
      disease.

PMID- 9010259
TI  - Thiol compounds inhibit mercury-induced immunological and immunopathological
      alterations in susceptible mice.
AB  - In vitro mercury induces a high proliferative response in splenic lymphocytes and
      in vivo it induces a systemic autoimmune disease in susceptible mouse strains.
      This disease is characterized by increased serum levels of IgE and IgG1
      antibodies, by the production of anti-nucleolar antibodies and by the formation
      of renal immune complex deposits. We have previously found that the presence of 2
      mercaptoethanol (2-ME) inhibited mercury-induced cell proliferation in vitro. In
      this study, we tested the effects of four other thiol compounds, namely
      dithiothreitol (DTT), L-cysteine, meso-2,3-dimercaptosuccinic acid (meso-DMSA)
      and 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS) on mercury-induced
      immunological changes both in vitro and in vivo. We found that in vitro, the
      addition of all thiol compounds abrogated mercury-induced cell aggregation and
      proliferation. In vivo, injection of meso-DMSA and/or DMPS (s.c. or i.p.)
      immediately following exposure to mercury markedly decreased IgG1 synthesis in
      spleen cells and serum IgE levels in mercury-susceptible SJL mice. Treatment with
      DMPS also prevented mercury-induced IgG1 anti-nucleolar antibody synthesis and
      the development of mesangial IgG1 immune complex deposits in SJL mice.

PMID- 9010260
TI  - Cytotoxic effect of autocrine and macrophage-derived nitric oxide on cultured rat
      mesangial cells.
AB  - Expression of the inducible form of nitric oxide synthase (iNOS) has been found
      to be up-regulated in cytokine-stimulated mesangial cells (MC) and in
      experimental glomerulonephritis. Since direct toxicity of nitric oxide (NO) has
      been implicated in damage of bacteria, neoplastic and intact pancreatic cells, we
      investigated whether NO is cytotoxic to cultured MC, which may be relevant to
      pathogenesis of glomerular injury. MC isolated from rat glomeruli generated
      substantial amounts of nitrite, the stable NO end-product, when cells were
      stimulated with IL-1beta and tumour necrosis factor-alpha (TNF-alpha). Total DNA
      synthesis was significantly reduced in the presence of IL-1beta and TNF-alpha,
      and this effect was completely reversed by N(G)-monomethyl-L-arginine (L-NMMA),
      an inhibitor of iNOS. Stimulation of MC with IL-1beta and TNF-alpha caused
      remarkable toxicity to these cells, measured by the MTT test (3-(4,5
      dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide cleavage, specific
      cytotoxicity 41.5 +/- 20.3%), and much less prominent MC lysis (3H-thymidine
      release, specific cytolysis 11.5 +/- 5.3%). Toxic effects of cytokines were fully
      reversible by the iNOS inhibitor. Lipopolysaccharide (LPS) and interferon-gamma
      (IFN-gamma), but not IL-1beta and TNF-alpha, induced rat peritoneal macrophages
      to produce large amounts of nitrite. In co-culture, such prestimulated
      macrophages had significantly cytotoxic (MTT test 62.9 +/- 19.9%) and cytolytic
      (3H-thymidine release 57.9 +/- 13.8%) effects on MC. Again, this toxicity was
      totally inhibited in the presence of L-NMMA. We conclude from these results that
      cytokine-stimulated generation of NO by MC or macrophages is directly toxic to
      MC, and may play a role in pathogenesis of glomerular injury involving
      mesangiolysis.

PMID- 9010261
TI  - Hepatitis C virus (HCV)-induced IgG-IgM rheumatoid factor (RF) complex may be the
      main causal factor for cold-dependent activation of complement in patients with
      rheumatic disease.
AB  - A low serum complement level is commonly found in patients with rheumatic
      diseases. We evaluated 170 patients with such diseases to determine their serum
      levels of CH50, C3 and C4 protein. Persistent hypocomplementaemia was found in 19
      of those patients, particularly in those with systemic lupus erythematosus (SLE).
      Cold-dependent activation of complement (CDAC) was demonstrated in nine of the 19
      (47.4%), and six of the nine patients demonstrated infection with HCV (66.7%).
      The nine patients that exhibited CDAC had nearly normal haemolytic complement
      activity when the sera were separated either at 37 degrees C or in EDTA-treated
      plasma. Conversely, it markedly decreased, even to the point of being
      immeasurable, when the sera were separated at 4-21 degrees C. No significant
      deficiency in C3 and C4 protein levels was found in these patients. Clinical
      parameters other than levels of anti-HCV antibody, transaminase, and RF were not
      influenced by CDAC. In an attempt to isolate the causal factor for CDAC, we
      isolated IgG fractions from the CDAC patients by using a protein G column, in
      which case precipitates were collected from the eluates. The precipitates were
      mixed with normal serum and incubated at 4-21 degrees C for 18 h. A decrease in
      the level of CH50 in normal serum was observed, which predominated (P < 0.001)
      when precipitates from HCV-infected patients were used. This indicated CDAC was
      possibly interrelated to the precipitates of such patients. This precipitate was
      proved to contain IgM besides IgG. It is therefore possible that an HCV-related
      IgG complex or an IgG-IgM RF complex may be formed at low temperature and be
      involved in activating the complement system in vitro.

PMID- 9010262
TI  - Serum levels of soluble Fas/APO-1 (CD95) and its molecular structure in patients
      with systemic lupus erythematosus (SLE) and other autoimmune diseases.
AB  - There are two major forms of the Fas molecule, membranous Fas and soluble Fas
      (sFas). To clarify the clinical significance of sFas in autoimmune diseases, we
      designed a sandwich ELISA to determine serum concentrations of sFas and its
      molecular structure, and we then analysed the correlation between levels of sFas
      and laboratory findings in patients with SLE and other autoimmune diseases. The
      levels of serum sFas were significantly higher in SLE patients than in subjects
      with other autoimmune diseases and in healthy donors, and the frequency of a
      positive serum sFas was much greater in SLE patients with high SLE disease
      activity index scores than in those with low scores. In addition, sFas-positive
      SLE patients showed a significant difference in various laboratory parameters
      from sFas-negative SLE patients. Serial measurements of serum sFas levels in SLE
      patients with active disease revealed that the elevated level of sFas
      dramatically decreased with improvement in clinical and laboratory findings,
      following corticosteroid therapy. We propose that the serum level of sFas can
      serve as an appropriate marker for evaluating SLE disease activity. Serum sFas is
      heterogeneous with respect to molecular structure, thus several mechanisms are
      involved in the generation of sFas.

PMID- 9010263
TI  - Modulation of hu/mu severe combined immunodeficient (SCID) mouse arthritis by
      local application of human recombinant IL-1beta, IL-2 and IL-6.
AB  - The contribution of interleukins produced by most inflammatory cells to chronic
      arthritis is not well understood. Therefore, we investigated the influence of
      several human recombinant interleukins (IL-1beta, IL-2 and IL-6) on joint
      swelling, on the inflammatory process, and on serological parameters in a novel
      animal model of arthritis, the human/murine SCID arthritis. In this model an
      arthritis is induced by implanting human synovial tissue from patients with
      rheumatoid arthritis (RA) into the knee joint of mice with SCID. These mice
      tolerate the xenogeneic implant and develop a mixed human/murine pannus tissue.
      The interleukins were injected daily for 7 or 14 days after implantation. IL
      1beta led to a significant increase in joint swelling. It intensified the
      inflammatory process accompanied by enhanced migration of murine inflammatory
      cells into the knee joint. The production of human IL-6 in the transplanted
      tissue was stimulated through the application of IL-1beta, and the serum level of
      human IL-6 was thus significantly higher than in controls. We could not observe a
      significant influence of IL-1beta on the production of human IgG or IgM by the
      implant. The application of human IL-2 had a weak effect similar to that of IL
      1beta, but without statistical significance. Although IL-6 is a good marker for
      inflammation in RA, the application of recombined human IL-6 had no influence on
      the inflammatory process in this model.

PMID- 9010265
TI  - Dynamic expression of transforming growth factor-betas (TGF-beta) and their type
      I and type II receptors in the synovial tissue of arthritic rats.
AB  - A well characterized animal model that shares many characteristic features with
      rheumatoid arthritis (RA) is collagen-induced arthritis (CIA) in DA rats. Recent
      studies have demonstrated that TGF-beta, a multifunctional cytokine, is an
      important modulator of the immune response in CIA, and possibly also in RA. In
      this study we have investigated the expression of the precursor forms of TGF
      beta1, TGF-beta2, TGF-beta3, as well as TGF-beta type I receptor (TGF-betaRI) and
      TGF-beta type II receptor (TGF-betaRII) in the synovial tissue of arthritic rats
      during the course of the disease. By using immunohistochemical techniques, an
      abundant expression of all three TGF-beta isoforms and their receptors was
      observed in the arthritic synovia, an expression that increased with time after
      onset of disease. Antibodies to TGF-beta1, TGF-beta2, TGF-betaRI and TGF-betaRII
      stained blood vessels intensively, already at the early onset of inflammation,
      whereas the synovial lining layer and chondrocytes expressed strong
      immunoreactivity later on in the inflammatory process. The most intense staining
      with these antibodies was detected in fibroblasts within fibrotic tissue, in
      particular at the cartilage pannus junction. Interestingly, TGF-beta3 only
      stained macrophage-like cells and chondrocytes in the synovia. The data suggest
      that the abundant expression of TGF-beta1, TGF-beta2, TGF-beta3 as well as TGF
      betaRI and TGF-betaRII in the synovia, is of pathogenic importance in the
      development of CIA, although the question of how the different TGF-beta isoforms
      may enhance or counteract different arthritogenic events remains open.

PMID- 9010264
TI  - The in vivo induction of lymphocyte apoptosis in MRL-lpr/lpr mice treated with
      FTY720.
AB  - The in vitro treatment of lpr thymocytes with FTY720 resulted in a dose-dependent
      reduction in cell viability due to apoptosis. In order to study the effect of
      FTY720 in vivo, lpr mice received an oral daily dose of 1 mg/kg FTY720 for 14
      days, beginning at 16 weeks of age which was when the animals were developing
      massive lymphoadenopathy. Compared with untreated lpr mice, FTY720-treated lpr
      mice had significantly prolonged lives. At 24 weeks of age, treated mice
      demonstrated markedly reduced weights of the spleen and lymph nodes, and the
      proportion of CD3+ B220+ and CD4- CD8- cells in the thymus, spleen and lymph
      nodes decreased markedly. In addition, in these mice the percentage of CD4+ CD8+
      and CD3- B220- cells in the thymus and the percentage of CD4+ CD8-, CD4- CD8+,
      CD3+ B220- and CD3- B220+ cells in the spleen returned to almost the normal
      values observed in wild-type mice. Histological observation 1 day after the final
      administration of FTY720 revealed a remarkable infiltration of neutrophils in the
      lymphoid organs. Apoptotic cells were detected in all the lymphoid organs using
      in situ DNA nick-end labelling. Electron microscopy showed that the apoptotic
      cells were ingested by phagocytes. FTY720 therapy is thus highly effective in Fas
      mutant animals with abnormally expanding lymphocytes.

PMID- 9010266
TI  - Antibodies to endothelial cells in Kawasaki disease lyse endothelial cells
      without cytokine pretreatment.
AB  - Kawasaki disease (KD) is characterized by diffuse vasculitis and marked immune
      activation. To confirm the presence of antiendothelial cell antibodies (AECA) and
      cytotoxicity of AECA, we investigated the presence of AECA using ELISA and
      cytotoxicity of AECA in KD. Sera from patients with acute KD were assessed for
      binding to human umbilical vein endothelial cells (HUVEC) using a cell-based
      ELISA, and for cytotoxicity against HUVEC as indicated by the conversion of a
      tetrazolium salt (MTT) into a coloured product. IgM AECA were detected in 8/19 KD
      sera, IgG AECA were detected in 5/19 KD sera. Significant differences in both
      AECA titres existed between patients and febrile and afebrile controls. Six out
      of 19 patients showed complement-dependent cytotoxicity against HUVEC.
      Cytotoxicity was significantly enhanced by pretreating HUVEC with tumour necrosis
      factor (TNF), and reduced by incubation with gammaglobulin. Serum titres of IgM
      AECA in the KD patients were positively correlated with cytotoxicity. Findings
      suggest that IgM AECA mediates complement-dependent cytotoxicity against
      endothelial cells in patients with KD, and gammaglobulin may reduce complement
      dependent cytotoxicity of AECA against endothelial cells.

PMID- 9010267
TI  - Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies.
AB  - Myeloperoxidase (MPO) is one of the main antigen targets of anti-neutrophil
      cytoplasmic antibodies (ANCA) in systemic vasculitides. It has been suggested
      that anti-MPO antibodies may recognize a single epitope on recombinant MPO. If
      confirmed on native MPO, this might allow specific therapeutic intervention with
      anti-idiotypic MoAbs to prevent antibody antigen interaction which is thought to
      cause activation of neutrophils and vasculitis. We searched for restriction in
      the epitope recognition profile in 50 patients with anti-MPO autoantibodies,
      using both native and recombinant MPO. Mouse monoclonals were purified and tested
      in competition assays. At least four epitopes were identified on native MPO using
      these monoclonals and only two were conserved on recombinant MPO. We found that
      human MPO autoantibody response was not restricted to a single epitope on native
      MPO, as all sera tested did not show the same profile in competitive studies with
      monoclonals. Furthermore, 30% of human anti-native MPO sera failed to recognize
      rMPO.

PMID- 9010268
TI  - Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA)
      in ulcerative colitis: non-histone chromosomal proteins, HMG1 and HMG2.
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from ulcerative colitis
      (UC) patients have been described as reacting with proteins in the granules of
      human neutrophils such as cathepsin G and lactoferrin and with yet unidentified
      antigens. Here we report the existence of a new member of perinuclear ANCA (P
      ANCA) in UC patients. In the previous study, we found that UC patients had a
      novel P-ANCA against neutrophil 28-kD protein. In this study, we purified the
      same antigens from HL-60 lysates by using reversed phase high-performance liquid
      chromatography, and revealed that the 28-kD antigen consisted of two different
      proteins. The N-terminus amino acids of these proteins are identical with those
      of high mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2.
      Immunoblotting analysis of human neutrophil lysates using rabbit anti-HMG1/2
      antisera revealed a single band of 28 kD, and the 28-kD band detected by
      immunoblotting analysis using patient's serum IgG completely disappeared after
      preincubation with a mixture of HMG1 and HMG2. Furthermore, rabbit anti-HMG1/2
      antisera showed a perinuclear staining pattern in indirect immunofluorescence
      studies using ethanol-fixed neutrophils. These data demonstrate that HMG1 and
      HMG2 are novel target antigens of P-ANCA. HMGI and HMG2 are distributed in the
      nuclei and cytoplasm of eukaryotic cells and act as transcription factors. Their
      intracellular localization and functions are distinct from those of the
      previously reported granular antigens of P-ANCA.

PMID- 9010269
TI  - Increased proinflammatory cytokine gene expression in the colonic mucosa of
      coeliac disease patients in the early period after gluten challenge.
AB  - Activation of T cells in the intestinal mucosa in response to gluten exposure is
      thought to play a key role in the pathogenesis of coeliac disease. Moreover, the
      response of the rectal mucosa to gluten challenge has been considered a useful
      predictor of gluten sensitivity in coeliac disease. In the present study, we
      assessed early changes in the expression of proinflammatory cytokine genes and
      the T cell receptor (TCR) Vbeta repertoire in the rectal mucosa of coeliac
      disease patients following experimental gluten challenge. Cytokine gene
      expression was assessed in rectal mucosal biopsies from coeliac disease subjects
      and controls before and after rectal gluten challenge using quantitative reverse
      transcription polymerase chain reaction analysis, and the TCR Vbeta repertoire
      was characterized using a multiprobe RNase protection assay. Marked up-regulation
      of expression of the C-X-C chemokine IL-8, the proinflammatory cytokine IL-1beta,
      and the C-C chemokine monocyte chemotactic protein-1 occurred within 24 h of
      rectal gluten challenge in coeliac disease subjects, but not in controls.
      Furthermore, these changes occurred in the absence of parallel changes in the
      expressed repertoire of TCR Vbeta genes in the rectal mucosa. Thus, an increased
      expression of proinflammatory cytokine genes precedes the expansion of antigen
      specific T cell populations in the early period following experimental exposure
      of the rectal mucosa of coeliac disease patients to gluten. These findings
      provide new insights into pathways that may be involved in the activation or
      reactivation of coeliac disease.

PMID- 9010270
TI  - Distinct delta T cell receptor repertoires in monozygotic twins concordant for
      coeliac disease.
AB  - One of the hallmarks of coeliac disease, both active and treated, is an increased
      number and proportion of gamma/delta intraepithelial T lymphocytes in the small
      intestinal mucosa, and an increased number of gamma/delta T cells in the small
      intestinal mucosa of coeliac disease patients has been associated with the
      inheritance of specific HLA class II DQ alleles. Nonetheless, the contribution of
      genetic factors to the development of the T cell receptor (TCR) delta repertoire
      in coeliac disease is not known. We have assessed the contribution of genetic
      factors to development of the TCR delta repertoire in coeliac disease, by
      characterizing the junctional diversity of TCR delta transcripts expressed in the
      intestine and peripheral blood of a pair of monozygotic (MZ) twins concordant for
      coeliac disease. TCR Vdelta1, Vdelta2 and Vdelta3 transcripts from small
      intestinal and colon biopsies, and from peripheral blood mononuclear cells, were
      amplified by polymerase chain reaction (PCR) and the complementarity determining
      region (CDR)3 domains of TCR delta transcripts were analysed by denaturing PAGE
      and direct nucleotide sequencing. The repertoire of TCR delta transcripts and
      CDR3 amino acid motifs in the intestine and peripheral blood of MZ twins
      concordant for coeliac disease exhibited no overlap. The TCR delta repertoire in
      each twin was oligoclonal, and complexity of the junctional regions of their TCR
      delta transcripts was typical of the repertoire in healthy adults. Thus,
      genetically identical individuals with coeliac disease have distinct, non
      overlapping TCR delta repertoires. Moreover, genetic factors that determine
      disease susceptibility do not appear to select for specific TCR delta sequences
      or CDR3 amino acid motifs.

PMID- 9010271
TI  - IgG and IgA subclass mRNA-bearing plasma cells in periodontitis gingival tissue
      and immunoglobulin levels in the gingival crevicular fluid.
AB  - The humoral immune response, especially the production of IgG and IgA, is
      considered to have a protective role in the pathogenesis of periodontal disease,
      but the precise mechanisms are still unknown. In order to determine local IgG and
      IgA production, we investigated the presence of human IgG and IgA subclass mRNA
      bearing plasma cells within periodontal tissue by in situ hybridization using
      digoxigenin-labelled oligonucleotide probes in 24 gingival biopsy samples (pocket
      depth > or = 5 mm) which were obtained from eight patients with adult
      periodontitis. Furthermore, we examined IgG and IgA subclass proteins and
      digested IgA1 Fab portions in the gingival crevicular fluid (GCF), corresponding
      to the sites from which the tissues were taken, by ELISA. IgG and IgA subclass
      mRNA-expressing cells were detected in all serial formalin-fixed/paraffin
      embedded gingival tissue sections sampled. Plasma cells showed strong cytoplasmic
      staining with a high contrast and a good retention of morphology with these
      probes. IgG1 mRNA-expressing cells were predominant (mean 63%) and IgG2 mRNA
      expressing cells were present at around 23% of total IgG plasma cells, while IgG3
      and IgG4 mRNA-expressing cells were present to a much lesser extent (3% and 10%,
      respectively). Similar proportions of IgG subclass proteins in GCF were detected,
      which were also consistent with 'normal' serum levels. In terms of IgA subclass,
      IgA1 mRNA-positive cells were predominant (mean 65.1%, P < 0.001). In contrast,
      IgA2 protein in the GCF samples were detected at higher concentrations than IgA1
      (P < 0.001). The ratio of total IgG to IgA mRNA-positive plasma cells was
      approximately 7.5:1. There was a good correlation between the amounts of IgG
      subclass proteins in GCF and the number of IgG subclass mRNA-positive cells in
      the same sites, but not between IgA subclass proteins and the number of IgA
      subclass mRNA-positive cells. These data suggest that IgG and IgA subclass
      proteins can be locally produced in the periodontitis gingiva. In addition, as we
      detected IgA1 Fab fragments in GCF, this is further confirmation that secreted
      IgA1 protein in GCF may be digested by periodontal bacteria.

PMID- 9010272
TI  - Relevance of local Th2-type cytokine mRNA expression in immunocompetent
      infiltrates in inflamed gingival tissue to periodontal diseases.
AB  - It has been suggested that the types of inflammatory round cell infiltrates and
      the divergence in the cytokine production profile by macrophages and helper T
      cells regulate the course of infectious or inflammatory diseases, including
      periodontitis and gingivitis. We examined the expression of IL-1alpha, IL-1beta,
      IL-2, IL-4, IL-5, IL-6 and tumour necrosis factor-alpha (TNF-alpha) mRNA in the
      inflamed gingiva by in situ hybridization. The results of single-cell analysis
      were used as data sets for statistical analyses. The density of cells expressing
      IL-1alpha, IL-4 and IL-5 mRNA was higher in periodontitis than in gingivitis. IL
      2 mRNA-expressing cells were almost absent in gingivitis specimens. Principal
      component analysis disclosed three factors explaining 84.8% of the variance: one
      accounting for 40.5% of the variance and mainly regulated by IL-1alpha, IL-1beta,
      IL-6 and TNF-alpha, and two others, explaining 29.9% and 14.4% of the variance,
      describing the relationship between the types of cytokines derived from
      macrophages or Th2 type. These results suggest that the cytokines produced by
      inflammatory cells infiltrating in the gingival tissue are influential on the
      progression of gingivitis, an acute and reversible inflammatory condition, to
      chronic and destructive periodontitis. Thus, periodontal disease progression may
      be regulated by the local cytokine network, and the bias in this network towards
      a Th2-type cytokine dominance could be an exacerbating factor.

PMID- 9010273
TI  - Increased IL-6 and IL-8 in bronchoalveolar lavage fluids (BALF) from patients
      with sarcoidosis: correlation with the clinical parameters.
AB  - A variety of cytokines have been implicated in the pathogenesis of pulmonary
      sarcoidosis, but the exact roles of IL-6 and IL-8 are not yet clear. We studied
      these cytokine levels in BALF from patients with pulmonary sarcoidosis,
      idiopathic pulmonary fibrosis (IPF), systemic screlosis (SSc) with interstitial
      lung disease and control subjects. IL-6 and IL-8 levels were significantly
      elevated in sarcoidosis, IPF and SSc with interstitial lung disease compared with
      control subjects. Subjects with sarcoidosis had significantly increased levels of
      both cytokines compared with controls when the cytokine values were corrected by
      the total albumin content and the two cytokine levels correlated with each other
      (r = 0.876). BALF IL-6 levels correlated with percent lymphocytes and percent
      CD3+ cells. Moreover, when sarcoidosis patients were divided into three groups,
      those who needed steroid therapy or had progressive disease showed increased
      cytokine levels in BALF over stable or improved patients. These observations
      suggest that locally derived IL-6 and IL-8 were increased in sarcoidosis and
      correlated with activity of this granulomatous lung disease.

PMID- 9010275
TI  - Age- and sex-related resistance to chronic experimental autoimmune myasthenia
      gravis (EAMG) in Brown Norway rats.
AB  - The influence of age and sex on the induction of chronic EAMG was analysed. Aged
      male rats, immunized with Torpedo acetylcholine receptor (tAChR), showed no
      clinical signs of disease or AChR loss. Immunization of young male Brown Norway
      (BN) rats resulted in both clinical signs of disease and 65% AChR loss. In
      contrast, both young and aged female BN rats showed comparable AChR loss (58% and
      50%, respectively), although aged female rats did not develop clinical signs of
      disease. Differences in antibody titres, isotype distribution, fine specificity
      or complement activation could not account for the observed resistance. These
      results suggest that resistance against EAMG in aged rats is due to resistance of
      the AChR against antibody-mediated degradation, or to mechanisms able to
      compensate for AChR loss.

PMID- 9010274
TI  - IL-6 and soluble IL-6 receptors (sIL-6R and sgp130) in human pleural effusions:
      massive IL-6 production independently of underlying diseases.
AB  - IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) levels were
      measured in sera and pleural effusions from 42 patients with metastatic
      carcinoma, non-Hodgkin's lymphoma, tuberculosis, cardiac failure and
      miscellaneous diseases. Pleural IL-6 levels measured by ELISA were very high in
      all patient groups (mean 34.8 +/- 15.3 ng/ml) without significant difference
      according to diseases. IL-6 was shown to be biologically active in a
      proliferative assay. Serum IL-6 levels were low (0.049 +/- 0.014 ng/ml) and did
      not correlate with pleural fluid levels. Pleural IL-6 levels correlated with the
      number of polymorphonuclear cells in pleural fluid (P < 0.03). Pleural sIL-6R
      levels (76 +/- 8 ng/ml) were always lower than serum levels (196 +/- 12 ng/ml; P
      < 0.0001) but correlated with them (P < 0.01). Pleural sIL-6R and albumin levels
      correlated (P < 0.01), suggesting a transudation of sIL-6R from the serum.
      Pleural sgp130 levels (10.9 +/- 1.0 ng/ml) were lower than serum levels (24.6 +/-
      2.8 ng/ml; P < 0.002). After gel filtration of pleural fluid, the bulk of IL-6 (>
      90%) was recovered in a 15,000-30,000 fraction, corresponding to the expected
      mol. wt of free IL-6. These results suggest a production and a sequestration of
      IL-6 in the pleural cavity in all studied conditions.

PMID- 9010276
TI  - IL-5 but not interferon-gamma (IFN-gamma) inhibits eosinophil apoptosis by up
      regulation of bcl-2 expression.
AB  - In order to determine regulatory mechanisms of eosinophil apoptosis, we examined
      the effect of recombinant IL-5 and interferon-gamma (IFN-gamma) on eosinophil
      apoptosis and bcl-2 expression. rhIL-5 (2.5 ng/ml) significantly inhibited
      eosinophil apoptosis in 96 h in vitro culture compared with medium only-cultured
      eosinophils (89.4 +/- 3.6% versus 31.3 +/- 12.2% (mean +/- s.d.); n = 7, P <
      0.05). Further, rhIL-5 significantly increased bcl-2 protein and mRNA expression
      on cultured eosinophils. A phosphorothioate antisense oligonucleotide targeted at
      the ATG translation initiation codon of bcl-2 (10(-5) M) could significantly
      block the supportive effect of rhIL-5 (0.25 ng/ml) for eosinophil survival
      compared with sense cDNA of bcl-2 on 96 h culture (inhibition rate 28.01 +/-
      4.56% versus 0.07 +/- 1.73%; n = 4, P < 0.05). In contrast, rhIFN-gamma (100
      U/ml) significantly inhibited eosinophil apoptosis on 96 h in vitro culture (72.7
      +/- 10.5%; n = 7, P < 0.05), but did not significantly up-regulate bcl-2 protein
      and mRNA. These results indicate that IL-5 has inhibitory effects on eosinophil
      apoptosis by regulation of bcl-2 expression.

PMID- 9010277
TI  - Low density lipoprotein receptor expression and function in human
      polymorphonuclear leucocytes.
AB  - Low density lipoprotein receptors (LDLR), capable of internalizing LDL, are
      expressed in polymorphonuclear neutrophils (PMN). The expression was assessed
      using anti-LDLR antibody by flow cytometry. The internalization of LDL was
      assessed by: (i) quantification of the uptake of labelled LDL with 1,1'
      dioctadecyl-3,3,3',3' tetramethyl-indocarboxycyanine perchlorate (DiI) by flow
      cytometry; and (ii) the binding of LDL-125I. In fresh purified cells, Lineweaver
      Burk analysis of LDL binding (LDL-DiI) revealed that the calculated Kd
      (internalized LDL) for PMN (15.0 x 10(-9) M) is lower than the Kd for monocytes
      (1.1 x 10(-7) M) and the Kd for lymphocytes (3.2 x 10(-7) M). Scatchard analysis
      (LDL-125I) revealed 25,000 binding sites and a Kd of 9.6 x 10(-9) M for PMN. The
      interaction of LDL with its receptor caused a two-fold fast (peak at 1 min) and
      transient increase in the oxidative burst, measured by the formation of 2',7'
      dicholoflurescein (DCF) by flow cytometry. This effect was not observed in
      monocytes or lymphocytes, and it was blocked by anti-LDLR antibody. The
      stimulation of LDL was optimal at 10 microg of protein/ml. LDL was able to
      suppress DCF formation induced by phorbol myristate acetate (PMA) and PMA was
      unable to further stimulate LDL-treated cells, suggesting protein kinase-C (PKC)
      involvement in LDL effects. Using a PKC assay, LDL was shown to induce a two-fold
      increase in PKC translocation to the membrane. Thus, LDL increases PMN oxidative
      burst through a PKC-dependent pathway.

PMID- 9010278
TI  - In contrast to their murine counterparts, normal human keratinocytes and human
      epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein.
AB  - In mice, keratinocyte-derived IL-10 is up-regulated by ultraviolet-B (UVB)
      radiation and plays a major role in UVB-induced immunosuppression. The present
      study was designed to examine whether a comparable phenomenon can be detected in
      man. Freshly isolated or cultured normal human keratinocytes (NHK) and
      keratinocyte cell lines A431 and HaCaT were stimulated with graded doses of UVB
      (up to 200 J/m2) or with a variety of other stimuli. RNA was extracted at various
      time points post-stimulation and analysed by reverse transcriptase-polymerase
      chain reaction (RT-PCR) using four different IL-10-specific primer pairs and RNA
      from monocytes or T cells as positive controls. We failed to detect IL-10 mRNA in
      NHK from 40 different donors (breast, abdomen, leg, scalp, foreskin) and in A431
      and HaCaT cells, irrespective of the stimulation used and despite successful
      stimulation. Supernatants of NHK, A431 and HaCaT cultures were negative for IL-10
      protein, as tested by four different ELISAs and a bioassay. Murine keratinocytes,
      stimulated under comparable conditions and tested by the same techniques,
      displayed a strong expression of IL-10 mRNA and protein. Remarkably, an IL-10
      mRNA signal could be detected in NHK after a second round of PCR amplification.
      Because NHK suspensions are contaminated with Langerhans cells, melanocytes and
      possibly fibroblasts, we tested pure populations of each individual cell type to
      determine the origin of this IL-10 mRNA. Our results clearly indicate that NHK,
      Langerhans cells and fibroblasts fail to express IL-10 and that melanocytes are
      the principal source of IL-10 mRNA in normal human epidermis.

PMID- 9010279
TI  - Classification of enteroviruses based on molecular and biological properties.

PMID- 9010280
TI  - The cleavage activities of aphthovirus and cardiovirus 2A proteins.
AB  - The primary 2A/2B polyprotein cleavage of aphtho-and cardioviruses is mediated by
      their 2A proteins cleaving C-terminally. Whilst the aphthovirus 2A region is only
      16 aa (possibly 18 aa) long, the cardiovirus 2A protein is some 150 aa. We have
      previously shown that foot-and-mouth disease virus (FMDV) 2A is able to mediate
      cleavage in an artificial (chloramphenicol acetyltransferase/FMDV 2A/beta
      glucuronidase [CAT-2A-GUS]) polyprotein system devoid of any other FMDV sequences
      with high (approximately 85%), although not complete, cleavage. In this paper we
      show that insertion of upstream FMDV capsid protein 1 D sequences increases the
      activity. In addition, we have demonstrated that the cardiovirus Theiler's murine
      encephalomyelitis virus(TME) 2A protein, when linked to GUS in a single ORF, is
      able to cleave at its own C terminus with high efficiency--if not completely. The
      C-terminal 19 aa of TME 2A, together with the N-terminal proline residue of
      protein 2B, were inserted into the CAT/GUS artificial polyprotein system (in a
      single ORF). This recombinant [CAT-deltaTME2A-GUS] polyprotein was able to
      mediate cleavage with high (approximately 85%) efficiency--directly comparable to
      the activity observed when FMDV 2A was inserted. A similar insertion into [CAT
      GUS] of the C-terminal 19 aa of the cardiovirus encephalomyocarditis virus (EMC)
      2A, together with the N-terminal proline residue of protein 2B, produced a [CAT
      delta EMC2A-GUS] polyprotein which also mediated cleavage at approximately 85%.
      Analysis of the products of expression of these artificial polyproteins in a
      prokaryotic translation system did not, apparently, reveal any GUS cleavage
      product.

PMID- 9010281
TI  - Molecular characterization of virus-specific RNA produced in the brains of
      flavivirus-susceptible and -resistant mice after challenge with Murray Valley
      encephalitis virus.
AB  - Natural resistance to flaviviruses in mice is controlled by a single genetic
      locus, FIv, on chromosome 5. Although the mechanism of this resistance is not
      fully understood, it is believed to operate at the level of virus replication
      rather than the immune response. It has been hypothesized that enhanced
      production of viral defective interfering (DI) particles is responsible for a
      substantial reduction in the titres of infectious virus in resistant mice.
      However, this has never been established at the molecular level since such
      particles have not been isolated and characterized. We have studied the products
      of virus replication in the brains of flavivirus-susceptible C3H/HeJ (Flv(s)) and
      -resistant congenic C3H/RV (Flv(r)) mice after an intracerebral challenge (i.c.)
      with Murray Valley encephalitis (MVE) virus and have found no evidence for the
      accumulation of truncated viral RNA in the brains of resistant mice. All three
      major viral RNA species, the replicative intermediate (RI), replicative form (RF)
      and virion RNA (vRNA) together with a subgenomic RNA species of 0.6 kb, which has
      not been previously described, were present in the brains of both mouse strains.
      However, the viral RF and RI RNA forms preferentially accumulated in the brains
      of resistant mice. Thus, we confirm that the resistance allele Flv(r) interferes
      with discrete steps in flavivirus replication, although the precise mechanism
      remains to be determined.

PMID- 9010282
TI  - Characterization of monoclonal antibody-escape mutants of tick-borne encephalitis
      virus with reduced neuroinvasiveness in mice.
AB  - Escape mutants of tick-borne encephalitis (TBE) virus were selected using
      neutralizing monoclonal antibodies (MAbs) that react with three different and
      previously unrecognized epitopes in the envelope protein E of TBE virus. Two of
      these variants (V-IC3 and V-IE3) exhibited a significantly reduced reactivity
      with their selecting MAbs, as determined by ELISA, whereas with one variant (V
      IO3), reactivity was completely unchanged. Comparative sequence analyses
      demonstrated that each of the variants differed from the wild-type virus by a
      single amino acid substitution located at exposed positions within domains I, II
      and III of protein E. In the mouse model, all three mutants were still neuro
      virulent but exhibited a significantly reduced neuro-invasiveness after
      subcutaneous inoculation. Virus replication, however, was sufficient to induce a
      specific antibody response. The observed alterations in virulence properties were
      not associated with reduced growth rates in vertebrate cell cultures, but one
      variant (V-IE3) exhibited a small plaque phenotype. The mutation of variant V-IO3
      resulted in a temperature-sensitive phenotype and a significant elevation of the
      pH-threshold of the conformational change necessary for fusion activity.

PMID- 9010283
TI  - Purification and characterization of the NS3 serine protease domain of hepatitis
      C virus expressed in Saccharomyces cerevisiae.
AB  - cDNA encoding the putative core of the hepatitis C virus NS3 serine protease
      domain (residues 1-181 of NS3; NS3 (181)) was expressed as an N-terminally (His)6
      tagged fusion protein in Saccharomyces cerevisiae. NS3 (181) protease activity
      was found in soluble cell lysates, and the N-terminal metal-chelating domain
      facilitated the efficient purification of active enzyme, using immobilized metal
      affinity chromatography. The purified NS3(181), protease activity was
      characterized by assaying the trans-cleavage of in vitro transcription
      translation generated substrates, and subsequently a previously unobserved
      cleavage site within the NS5A region was identified. The inhibitory effect of
      known protease inhibitors was also examined. It is hoped that availability of
      this method for the expression and purification of the NS3(181) protease will
      facilitate the development of anti-hepatitis C therapies.

PMID- 9010284
TI  - Classification of hepatitis C virus variants in six major types based on analysis
      of the envelope 1 and nonstructural 5B genome regions and complete polyprotein
      sequences.
AB  - The phylogenetic status of recently described isolates of hepatitis C virus (HCV)
      from Vietnam, Thailand and Indonesia (previously classified as types 7, 8, 9, 10
      and 11) was re-analysed by the neighbour-joining method instead of the unweighted
      pair-group method with arithmetic mean (UPGMA) that was first used by the
      discoverers of these strains. The analysis of complete amino acid sequences and
      of nucleotide sequences of the envelope 1 (672 nt) and nonstructural 5B (1092 nt)
      genomic regions permitted the re-assignment of the type 7, 8, 9 and 1 1 isolates
      to type 6, and that of type 10 strains to type 3. Finally, this study made
      possible the classification of the previously described HCV strains (including
      these South-East Asian isolates) in six major types and at least 30 subtypes. It
      confirms that analysis of the E 1 and NS5B genomic regions using the neighbour
      joining method is a reliable tool for the assignment of most new isolates.

PMID- 9010285
TI  - Genetic diversity between hepatitis G virus isolates: analysis of nucleotide
      variation in the NS-3 and putative 'core' peptide genes.
AB  - Significant variation was found, between 46 isolates of hepatitis G virus (HGV),
      following direct sequencing of subgenomic PCR fragments from either or both the
      NS-3 and putative 'core' peptide. Nucleotide sequences of most HGV NS-3 fragments
      varied by 10-30% and of most putative 'core' peptide fragments by 2-20%. HGV was
      therefore shown to be much less variable than hepatitis C virus (HCV) and
      pairwise comparisons of HGV sequences demonstrated a single distinct distribution
      of evolutionary distances. Construction of phylogenetic trees, bootstrap analysis
      and calculation of mean distances between possible subtypes also indicated one
      level of variation between HGV NS-3 and putative 'core' peptide sequences, and
      the suggested degree of variation between isolates was similar to that between
      HCV subtypes. No evidence for clustering of sequences into multiple subtypes or
      genotypes was found. Although very small subgenomic fragments of HCV are
      indicative of the viral genotype it seems that the assignment of genetic groups
      is not possible for HGV using such small subgenomic fragments. The relatively
      limited genetic variation observed in HGV may reflect a relatively low level of
      host selection pressure stemming from the low level of host immunity stimulated
      by this virus.

PMID- 9010286
TI  - Mouse hepatitis virus strain A59 is released from opposite sides of different
      epithelial cell types.
AB  - Coronaviruses infect humans and animals through epithelial cells of the
      gastrointestinal and respiratory tracts that serve as their primary target. When
      studying infections in cultured polarized epithelial cells, we found previously
      that coronaviruses are released from specific plasma-membrane domains; thus,
      mouse hepatitis virus (strain A59; MHV-A59) leaves murine epithelial kidney cells
      from the basolateral surface, whereas release of transmissible gastroenteritis
      virus from porcine epithelial kidney cells is confined to the apical membrane.
      This observation begged the question whether a particular coronavirus is
      consistently shed through the same membrane, irrespective of the nature of the
      epithelial cell. We therefore extended our studies with MHV-A59 to Madin-Darby
      canine kidney (MDCK) strain I and human colon carcinoma (Caco-2) cells, both of
      which are naturally refractory to MHV-A59 but were made susceptible to infection
      by transfection with recombinant MHV receptor cDNA. The release of MHV-A59 from
      Caco(MHVR) cells occurred preferentially from the basolateral side, consistent
      with our previous observations. In contrast, release from MDCK(MHVR) cells
      occurred almost exclusively from the apical surface. Because of this difference,
      we studied MHV-A59 infection of MDCK(MHVR) cells in more detail. The virus
      entered the cells preferentially from the apical side, a situation similar to
      that in murine epithelial cells, where the highest density of MHV receptor
      glycoprotein was found. The results from this and previous studies show that
      targeting of vesicles containing MHV-A59 to a specific side of epithelial cells
      may vary in different epithelial cell types.

PMID- 9010287
TI  - Expression and characterization of a recombinant murine coronavirus 3C-like
      proteinase.
AB  - The replication of coronaviruses involves proteolytic processing of the gene 1
      translation products, pp1a and pp1ab. One of the key enzymes in this process is
      predicted to be a virus-encoded 3C-like proteinase. In this report, we describe a
      bacterial system that has allowed us to express and characterize a recombinant
      murine coronavirus (MHV-JHM) 3C-like proteinase. The partially purified protein
      has been shown to exhibit proteolytic activity in trans and mutation analysis has
      been used to demonstrate the indispensability of Cys-3495 for enzymatic activity.
      Finally, the effect of class-specific proteinase inhibitors on the trans cleavage
      activity of the MHV 3C-like proteinase has been used to demonstrate the
      functional and structural homology of this enzyme to the picornavirus 3C
      proteinases.

PMID- 9010288
TI  - Organization of the M genomic segment of Toscana phlebovirus.
AB  - The nucleotide sequence of the Toscana (TOS) virus M RNA segment contains a
      single major open reading frame in the viral-complementary sequence, which can
      encode a polyprotein of 1339 amino acids. To map the TOS M segment product(s),
      different regions of the putative M polypeptide were expressed as glutathione S
      transferase fusion proteins, which were purified and inoculated into mice to
      produce hyperimmune sera. By Western blot analysis, a protein of approximately 30
      kDa and two glycoproteins, G1 and G2, with the same molecular mass (approximately
      65 kDa) were identified in TOS virus-infected cells. The 30 kDa protein, which
      reacted with antibodies raised to the NH2-terminal, was found to be a non
      structural protein (designated NSm). By immunoprecipitation analysis of TOS virus
      infected cell lysates, both treated or untreated with tunicamycin, the relative
      positions of glycoproteins G1 and G2 were determined. The gene order, with
      respect to the genomic M RNA, was found to be 3' NSm-G1 -G2 5'

PMID- 9010289
TI  - An anti-fusion regulatory protein-1 monoclonal antibody suppresses human
      parainfluenza virus type 2-induced cell fusion.
AB  - Fusion regulatory protein-1 (FRP-1) regulates virus-mediated cell fusion and
      induces poly-karyocyte formation of monocytes without any fusogen. We have
      recently reported that FRP-1 and the 4F2/CD98 heavy chain are identical
      molecules. Cell fusion in Newcastle disease virus (NDV)-infected HeLa cells was
      enhanced when cells were incubated with anti-FRP-1 MAb. Anti-FRP-1 MAbs also
      induced human immunodeficiency virus gp160-mediated cell fusion. However, HBJ127,
      an anti-FRP-1/4F2/CD98 MAb that enhanced cell fusion in NDV-infected cells,
      delayed human parainfluenza virus type 2 (HPIV-2)-induced cell fusion in HeLa
      cells, although these viruses belong to the same genus Rubulavirus. No anti-FRP-1
      MAbs enhanced cell fusion in HPIV-2-infected HeLa cells. Anti-FRP-1 MAbs
      including HBJ127 showed no effect on virus growth and expression levels of virus
      specific poly-peptides in HPIV-2-infected HeLa cells, indicating that the delay
      in cell fusion by an anti-FRP-1 MAb is not due to suppression of virus
      replication. When HeLa cells were transfected with an expression vector
      harbouring HPIV-2 HN and F genes, cell fusion was also suppressed by HBJI27, but
      the effect was weak in comparison with virus-infected cells. These data indicate
      anti-FRP-1 antibodies not only induce/enhance, but also inhibit/delay virus
      induced cell fusion and therefore FRP-1 molecules are multifunctional.

PMID- 9010290
TI  - Characterization of five conserved genotypes of the mumps virus small hydrophobic
      (SH) protein gene.
AB  - Twenty-one different mumps virus isolates from Sweden and Japan collected over 25
      years were compared by nucleotide sequence analysis of the small hydrophobic (SH)
      protein gene, and the deduced 57 amino acid sequences of the coding part of the
      gene were aligned with published sequences of viral isolates from the USA, the
      UK, Sweden and Japan. Five genotypes were found which, in accordance with
      previously used nomenclature, were named A to E. Genotypes A, C, D and E were
      found in Europe and genotype B was found in Japan. Amino acid signature sequence
      motifs specific for each genotype were identified. A triplet of three amino acids
      at positions 28-30 was the most characteristic. Different genotypes can circulate
      simultaneously in a given geographical location. In Stockholm, genotypes A and D
      or C and D were found over different time periods. In contrast, only genotype B
      was found in Japan.

PMID- 9010291
TI  - Sequence divergence of measles virus haemagglutinin during natural evolution and
      adaptation to cell culture.
AB  - Phylogenetic analysis of the sequence of the H gene of 75 measles virus (MV)
      strains (32 published and 43 new sequences) was carried out. The lineage groups
      described from comparison of the nucleotide sequences encoding the C-terminal
      regions of the N protein of MV were the same as those derived from the H gene
      sequences in almost all cases. The databases document a number of distinct
      genotype switches that have occurred in Madrid (Spain). Well-documented is the
      complete replacement of lineage group C2, the common European genotype at that
      time, with that of group D3 around the autumn of 1993. No further isolations of
      group C2 took place in Madrid after this time. The rate of mutation of the H gene
      sequences of MV genotype D3 circulating in Madrid from 1993 to 1996 was very low
      (5 x 10(-4) per annum for a given nucleotide position). This is an order of
      magnitude lower than the rates of mutation observed in the HN genes of human
      influenza A viruses. The ratio of expressed over silent mutations indicated that
      the divergence was not driven by immune selection in this gene. Variations in
      amino acid 117 of the H protein (F or L) may be related to the ability of some
      strains to haemagglutinate only in the presence of salt. Adaptation of MV to
      different primate cell types was associated with very small numbers of mutations
      in the H gene. The changes could not be predicted when virus previously grown in
      human B cell lines was adapted to monkey Vero cells. In contrast, rodent brain
      adapted viruses displayed a lot of amino acid sequence variation from normal MV
      strains. There was no convincing evidence for recombination between MV genotypes.

PMID- 9010292
TI  - Inhibition of measles virus infection and fusion with peptides corresponding to
      the leucine zipper region of the fusion protein.
AB  - Measles virus (MV) infections are characterized by the induction of syncytia,
      i.e. the fusion of infected cells. Two MV proteins, the haemagglutinin (HA) and
      fusion (F) proteins, are involved in this process. Synthetic peptides
      representing two alpha-helical regions of the MV F protein were studied for their
      ability to inhibit MV fusion. A peptide corresponding to the leucine zipper
      region (amino acids 455-490) inhibited MV fusion, whereas a peptide to amino
      acids 148-177, corresponding to the amphipathic alpha-helix region, did not.
      Fusion inhibition was also obtained with vaccinia virus-expressed HA and F, a
      recent wild-type MV isolate and the closely related canine distemper virus, but
      not with mumps virus. The F455-490 peptide did not affect the synthesis of MV F
      or its transport to the cell membrane. Virus-cell attachment was unaffected, but
      haemolysis and virus entry into the cell were inhibited. In one-step growth
      curves the virus yield was unaffected.

PMID- 9010293
TI  - Distribution and variation of NV genes in fish rhabdoviruses.
AB  - The fish rhabdovirus infectious haematopoietic necrosis virus (IHNV) contains a
      non-virion (NV) gene between the glycoprotein (G) and polymerase (L) genes on its
      RNA genome. The present study investigated three other fish rhabdovirus genomes
      and found that the NV gene of hirame rhabdovirus is closely related to the NV of
      IHNV, whereas the viral haemorrhagic septicemia NV gene showed evidence of
      significant divergence. Most importantly, spring viraemia of carp virus, the only
      vesiculovirus-like fish rhabdovirus examined, did not have an NV gene at its
      genomic RNA G-L junction. These results suggest that the presence of an NV gene
      is characteristic of the unassigned fish rhabdovirus subgroup previously
      classified as lyssaviruses, and that the NV gene is not essential for replication
      in fish cells per se, since it is absent in a vesiculovirus-like fish
      rhabdovirus.

PMID- 9010294
TI  - Mapping of monoclonal antibody epitopes of the rabies virus P protein.
AB  - Thirty-six monoclonal antibodies (MAbs) specific for the rabies virus P
      phosphoprotein were obtained from mice immunized with recombinant P (PV strain)
      produced in E. coli. All MAbs reacted against the corresponding rabies virus
      protein by ELISA and by Western blot analysis and revealed the presence of
      cytoplasmic inclusions in rabies virus infected cells. The epitopes of seven MAbs
      were mapped by testing their reactivity with protein fragments expressed from
      deletion mutants in transfected cells. Western blotting, immunoprecipitation and
      immunofluorescence assays were performed. These MAbs recognized epitopes in
      different domains of the P protein: 60% were directed against a region lying
      between residues 83-172 suggesting a major antigenic determinant of the rabies
      virus P protein in this region. Most of the antigenic sites appeared to be
      composed of linear epitopes. These MAbs will be useful as tools to dissect
      structural and functional properties of the rabies virus P protein.

PMID- 9010295
TI  - Inhibition of vesicular stomatitis virus in cells constitutively expressing an
      antisense RNA targeted against the virus RNA polymerase gene.
AB  - To study the effect of virus-specific antisense RNA expression on vesicular
      stomatitis virus (VSV) infectivity in cultured cells, a HeLaS3 cell line
      constitutively expressing antisense RNA complimentary to a portion of the VSV
      large RNA-dependent RNA polymerase gene (L) was established (HeAntiL). At an
      m.o.i. of 0.01 or 0.1, the HeAntiL cell line was able to reduce virus titre and
      delay virus-induced cell death by 9 or 5 h, respectively, when compared to a HeLa
      cell line stably transfected with the expression vector devoid of antisense
      sequence. Ribonuclease protection experiments showed a 10-20-fold reduction of
      hybridizable virus L mRNA in infected HeAntiL cells compared to infected control
      cells at various times before cell death. These results indicate that the
      antisense RNA approach can significantly reduce VSV mRNA transcription and virus
      production for a reasonable period of time. The robust growth rate of VSV
      eventually overwhelms the available antisense RNA and leads to delayed cell
      death.

PMID- 9010297
TI  - Infection of choroid plexus cells by human T cell leukaemia virus type I.
AB  - Very little is known about the factors that determine the outcome of infection by
      human T cell leukaemia virus type I (HTLV-I) and the neurotropism of this virus
      is still a controversial point. In transgenic mice, the HTLV-I LTR is active
      mainly in the central nervous system (CNS), in parenchyma as well as in ependymal
      and choroid plexus cells. The latter are of particular interest and could
      represent the way of entry of the virus into the CNS. In this study we show that
      primary cultures of sheep choroid plexus can be infected with HTLV-I, leading to
      characteristic multinucleated syncytial cells containing virus RNA and proteins.
      HTLV-I p24 Gag protein was detected in the culture medium and the presence of
      virus particles was observed by electron microscopy 40 days after infection. At
      this time post-infection HTLV-I could be transmitted to human cord blood cells.

PMID- 9010296
TI  - Proteolytic activity in vivo and encapsidation of recombinant human
      immunodeficiency virus type 1 proteinase expressed in baculovirus-infected cells.
AB  - The activity in vivo of HIV-1 proteinase (PR) was analysed in the baculovirus
      expression system, using eight different constructs of the prt gene under the
      control of polyhedrin (PH) promoters of various strengths. None of the active PRs
      was expressed in substantial quantities, and only PH-fused and/or non-functional
      PR mutants accumulated in high amounts in insect cells. However, enough PR
      activity was generated from a lengthened PR construct in insect cells to process
      Gag polyprotein substrate co-expressed in the same cells in trans. Fusion of the
      first 58 residues from the PH sequence to the PR N terminus did not significantly
      change its activity and specificity of cleavage of the Gag substrate. When
      analysed under mild denaturing conditions, PH-fused or unfused full-length PR
      point mutants, as well as PH-fused or unfused C-terminal deletion mutants, showed
      a propensity to multimerize, with a predominant occurrence of dimers. The
      incorporation of PR into Gag particles was studied using eight Gag-PR fusion
      constructs, all containing a non-functional PR mutant. The PR domain was fused to
      the C-terminal p6 domain of Gag (p6gag), or translated in frame with NCp7 (as in
      frameshifted Gag-Pol polyprotein) and followed by downstream sequences of
      increasing lengths from the Pol domain or the bacterial beta-galactosidase. The
      results suggested that the presence of the p6gag domain was detrimental to the
      encapsidation of polyprotein-embedded PR.

PMID- 9010298
TI  - Long-term persistence of protective immunity in cynomolgus monkeys immunized with
      a recombinant vaccinia virus expressing the human T cell leukaemia virus type I
      envelope gene.
AB  - To develop effective vaccines against infection with human T cell leukaemia virus
      type I (HTLV-I), we constructed a recombinant vaccinia virus (WR-SFB5env)
      synthesizing the HTLV-I envelope (Env) gp46 protein under the control of a strong
      promoter, termed the ATI hybrid promoter. WR-SFB5env expressed a large quantity
      of gp46. In cynomolgus monkeys (Macaca fascicularis) immunized with WR-SFB5env,
      anti-HTLV-I Env antibody, including neutralizing antibody, was induced and
      remained at a high level until 136 weeks (2-6 years) post-infection (p.i.). These
      immunized monkeys had HTLV-I Env-specific cytotoxic T lymphocyte activity. At 136
      weeks p.i., the immunized monkeys were challenged with an HTLV-I-producing
      cynomolgus T lymphocyte cell line. Neither HTLV-I antigen nor HTLV-I proviruses
      were detected in peripheral blood mononuclear cells, lymph nodes or spleens of
      the WR-SFB5env-immunized monkeys, in contrast to non-immunized control monkeys.
      These results indicate that a single immunization with WR-SFB5env induced
      prolonged humoral and cellular immune responses to HTLV-I and protected the
      monkeys against virus challenge.

PMID- 9010299
TI  - Bovine leukaemia virus-induced lymphocytosis in sheep is associated with
      reduction of spontaneous B cell apoptosis.
AB  - Experimental inoculation of sheep with bovine leukaemia virus (BLV), a retrovirus
      homologous to the human T-lymphotropic virus type 1 (HTLV-1), induces a chronic
      expansion of the B lymphocyte population (persistent lymphocytosis) and the
      development of a B cell leukaemia/lymphosarcoma syndrome. To gain insight into
      the mechanisms of BLV-induced lymphocytosis, we tested B cell survival capacity
      and cycling activity in peripheral blood mononuclear cells (PBMCs) from
      lymphocytotic, asymptomatic and control sheep. Interestingly, B cells from
      lymphocytotic sheep presented a lower level of spontaneous apoptosis (29%) in ex
      vivo cultures compared to that obtained with infected asymptomatic (42%) and
      control (57%/o) sheep PBMCs. Virus capsid (CA) synthesis was mainly found among
      surviving B cells and the percentage of CA-producing B cells correlated with the
      extent of B cell survival, indicating that BLV replication in B lymphocytes may
      promote protection from cell death. B cell survival was not linked with increases
      in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are
      documented to be involved in some aspects of the B cell life-span. Finally, cell
      cycle analyses in freshly isolated PBMCs from lymphocytotic sheep revealed a
      slightly increased proportion of B cells in S phase compared to controls.
      Altogether, these data suggest that both BLV-induced B cell proliferation and
      extended survival are involved in the lymphocytotic stage encountered in BLV
      infection in sheep.

PMID- 9010300
TI  - Activity of JC virus archetype and PML-type regulatory regions in glial cells.
AB  - Sequence variations are seen in the JC virus promoter/enhancer in virus taken
      from progressive multifocal leukoencephalopathy (PML) brains and it has been
      hypothesized that the variations arise in the host at some point in the
      development of PML. These rearrangements may be adaptations for enhanced growth
      in glial cells; if so, transcription or replication levels should differ between
      archetypal and rearranged PML-type promoters. The archetype and four PML-type
      promoters were analysed in human glial cells for early and late transcriptional
      activity in the absence or presence of virus T antigen, and for DNA replication.
      CAT reporter expression differed within a fivefold range and the archetype was
      intermediate in strength to the PML-type regulatory regions. The archetype
      differed from rearranged promoters in that the late promoter was less responsive
      to T antigen and the shift from early to late activity with T antigen was less
      pronounced. All five regulatory regions demonstrated similar levels of DNA
      replicating activity. Rearrangement of the archetype was not required for
      activity in glial cells, but the potential for differences in the regulation of
      the late capsid genes was found.

PMID- 9010301
TI  - Casein kinase II phosphorylates bovine papillomavirus type 1 E1 in vitro at a
      conserved motif.
AB  - The E1 protein of bovine papillomavirus type 1 (BPV-1) is a phosphoprotein which
      specifically binds and unwinds the virus replication origin by ATP-dependent
      helicase activity. The El protein has been shown to be multiply phosphorylated in
      vivo, although the sites of modification are incompletely mapped. Examination of
      the predicted amino acid sequence of all available E1 proteins revealed strong
      conservation between amino acids 25 and 60 of a motif consisting of a serine
      residue followed by a stretch of acidic residues. This conserved motif resembled
      a phosphorylation consensus site for the ubiquitous cellular kinase casein kinase
      II (CKII). Biochemical and mutational analysis demonstrated that the BPV- 1 E1
      protein is an in vitro substrate for CKII at the serine within this conserved
      motif.

PMID- 9010302
TI  - Replacement of the herpes simplex virus type 1 Vmw175 DNA binding domain with its
      varicella-zoster virus counterpart results in a protein with novel regulatory
      properties that can support virus growth.
AB  - The alphaherpesviruses encode major immediate early transactivator proteins that
      are essential for the expression of later classes of viral genes. We have
      previously shown that the extensive sequence similarity between the herpes
      simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) members of the
      family (proteins Vmw175 and VZV140k) extends to function, since a virus which
      expresses VZV140k in place of Vmw175 is able to grow, albeit at reduced
      efficiency. We have also shown that the DNA binding characteristics of the
      isolated DNA binding domains of Vmw175 and VZV140k are related but distinct. In
      order to assess whether the different DNA binding properties of the two proteins
      are responsible for the differences in their individual transcriptional
      regulatory functions, we constructed a plasmid and an HSV-1 virus in which the
      VZV140k DNA binding domain coding sequences replace those of Vmw175. The
      characteristics of the resultant hybrid protein in transfection assays and during
      virus infection suggest that the nature of the DNA binding domain plays a
      significant role in the transactivation and repression properties of the Vmw1 75
      family of proteins.

PMID- 9010303
TI  - The abundance of the herpes simplex virus type 1 UL37 tegument protein in virus
      particles is closely controlled.
AB  - The tegument region of herpes simplex virus type 1 virus particles contains
      approximately 15 virus-encoded polypeptide species. One of the less abundant
      species is a 120 kDa protein specified by gene UL37. The abundance of the UL37
      protein in infected cells was increased about 20-fold by replacing the native
      promoter for gene UL37 with the strong immediate early promoter of human
      cytomegalovirus. This rise in abundance did not induce any detectable increase in
      the amount of UL37 protein incorporated into virus particles. These data contrast
      with those previously obtained for a second tegument protein VP22 whose level of
      incorporation was elevated by increasing its abundance in infected cells. Thus,
      for the UL37 protein, a mechanism exists to control its abundance in the
      tegument. Moreover, data obtained with light particles which lack the viral
      capsid suggest that this controlled incorporation is not directed by interaction
      with the capsid structure.

PMID- 9010304
TI  - Herpes simplex virus type 2 synergizes with interferon-gamma in the induction of
      nitric oxide production in mouse macrophages through autocrine secretion of
      tumour necrosis factor-alpha.
AB  - We have analysed the ability of herpes simplex virus type 2 (HSV-2) to induce
      nitric oxide (NO) production in resting BALB/c mouse peritoneal macrophages. In
      most experiments, macrophages produced very small amounts of NO upon infection
      with HSV-2. Mock virus preparations did not induce NO production, and virus
      inactivation experiments showed that infectious virus was required. Since
      interferon-gamma (IFN-gamma) is the prototype cytokine that is able to induce
      significant NO production in macrophages, we found it of interest to examine the
      influence of HSV-2 infection on the IFN-gamma-induced NO production. The virus
      exerted a synergistic effect on the IFN-gamma-induced NO release, which was
      accompanied by induction of the iNOS-gene as revealed by RT-PCR. This effect was
      largely dependent on the presence of infectious virus particles, since only a
      minor effect was seen with mock virus and inactivated virus preparations. From
      experiments with neutralizing antibodies to tumour necrosis factor-alpha (TNF
      alpha) and IFN-alpha/beta it was concluded that the synergistic effect is
      dependent on autocrine secretion of TNF-alpha, which acts as a second signal and
      synergizes with IFN-gamma in NO production.

PMID- 9010305
TI  - Transforming growth factor beta production during rat cytomegalovirus infection.
AB  - We analysed the production of transforming growth factor beta (TGF-beta) during a
      cytomegalovirus (CMV) infection in a rat model system. Splenocytes from
      immunocompetent rats infected with rat CMV (RCMV) released increased amounts of
      TGF-beta1. TGF-beta production was also evident in RCMV-infected radiation
      immunosuppressed rats; their sera inhibited the interleukin 2-induced
      proliferation of T cells, which could be restored by anti-TGF-beta antibodies. In
      addition, TGF-beta production could be visualized immunohistologically in the
      lungs, spleen, liver and bone marrow of radiation-immunosuppressed infected rats.
      The virus directly induced this cytokine since TGF-beta was produced upon RCMV
      infection in vitro. The induction of TGF-beta production may contribute to
      immunosuppression during CMV infection.

PMID- 9010306
TI  - Establishment of a cell line expressing human parvovirus B19 non-structural
      protein from an inducible promoter.
AB  - Human parvovirus B19 non-structural (NS) protein is supposed to play a major role
      in B19 replication and transcription, and therefore in B19 pathogenicity.
      Constitutive expression of NS protein in stable cell lines has failed so far,
      presumably because of its cytotoxicity. To avoid this cytotoxic effect, we have
      cloned the NS gene in an Epstein-Barr virus episomal vector under the control of
      a steroid inducible promoter (5xGRE) and transfected this construction into HeLa
      cells. We obtained stable cell lines inducibly expressing high level of NS
      protein, with 50% of the cells demonstrating specific nucleo-cytoplasmic
      staining. In Western blot analysis, three B19 NS proteins (72, 68 and 60 kDa)
      were found but a unique NS transcript was detected by Northern blotting. The NS
      protein expressed in HeLa cell lines was demonstrated to be functional as it
      trans-activates the B19 P6 promoter. These cell lines might be major tools for
      further study and characterization of B19 NS protein.

PMID- 9010307
TI  - Sequence of porcine circovirus DNA: affinities with plant circoviruses.
AB  - The complete nucleotide sequence (1759 nt) of the ssDNA genome of porcine
      circovirus (PCV) was determined from a cloned dsDNA replicative form isolated
      from PCV-infected cells. Sequence analysis detected no significant nucleic acid
      or protein similarity with another animal circovirus, chicken anaemia virus (CAV)
      but, surprisingly, the highest protein similarity was obtained between the
      product of the largest predicted PCV ORF (ORF1; encoding a potential protein of
      35.7 kDa) and a putative protein encoded by the plant circovirus banana bunchy
      top virus (BBTV). High protein similarity was also detected with the other plant
      circoviruses subterranean clover stunt virus (SCSV) and coconut foliar decay
      virus (CFDV). This region of protein identity corresponds with the putative plant
      circovirus replication-associated protein (Rep). The presence of a nonanucleotide
      sequence at the apex of a potential-stem loop structure, identical to that found
      in the plant circoviruses CFDV and SCSV and similar (one mismatch) to that found
      in the plant circovirus BBTV and in the geminiviruses, suggests that rolling
      circle replication may operate during PCV DNA replication. These findings show
      that PCV is unique in that it bridges the gap between animal and plant
      circoviruses. The taxonomic relationship of PCV with other members of the
      Circoviridae is discussed.

PMID- 9010308
TI  - Two mRNAs are transcribed from banana bunchy top virus DNA-1.
AB  - We have mapped the mRNA transcripts of banana bunchy top virus (BBTV) DNA-1.
      Northern hybridization and 3' RACE analysis identified two poly-adenylated RNAs
      associated with BBTV DNA-1. Previously, one major ORF in the virion sense of DNA
      1 had been identified, which encoded a putative replication protein (Rep). An
      mRNA was identified in BBTV infected bananas that was clearly transcribed from
      this Rep ORF. Further, a second transcript was identified which mapped to an ORF
      completely within the Rep ORF. This encoded a putative 5 kDa protein of unknown
      function. Both these transcripts were also identified in a tobacco plant that had
      been transformed with Agrobacterium tumefaciens harbouring a binary construct
      containing the Rep ORF from BBTV DNA-1. This Rep ORF was inserted 3' of a
      cauliflower mosaic virus 35S promoter and 5' of a vegetable storage protein
      terminator. The transcripts mapped from these tobacco plants were identical at
      the 3' end to the transcripts from BBTV infected banana plants. The site of
      polyadenylation for the Rep ORF was at base 963 immediately 3' of the
      translational stop codon confirming that the polyadenylation signals for this
      transcript were all within the ORF. However, the internal ORF had a large
      untranslated region of 272 bases with its site of polyadenylation at nucleotide
      803 and a polyadenylation signal 3' of the translational stop codon. A possible
      upstream termination signal (A/TTGTAA) was identified and was conserved within
      BBTV DNA-1 sequences from different international isolates.

PMID- 9010309
TI  - In vivo expression of an overlapping gene encoded by the cucumoviruses.
AB  - We recently reported the molecular characterization and functional analysis of an
      overlapping gene 2b encoded by RNA 2 of the Q strain of cucumber mosaic
      cucumovirus (Q-CMV). We show here that the homologous gene encoded by the V
      strain of tomato aspermy cucumovirus (V-TAV) and the WAII strain of CMV (WAII
      CMV), which is in a different subgroup to Q-CMV, is also expressed in vivo by
      demonstrating the accumulation of the mRNA (RNA 4A) and its protein in infected
      plants. Interestingly, RNA 4A of V-TAV is encapsidated in virions as found
      previously for Q-CMV whereas WAII-CMV contains very little RNA 4A in virions. As
      the 2b gene is conserved in all 10 cucumoviral species or strains sequenced to
      date and the 2b gene is expressed for three of these viruses, we conclude that
      the 2b gene is a common feature of the Cucumovirus genus.

PMID- 9010310
TI  - Short and long distance spread of potato leafroll luteovirus: effects of host
      genes and transgenes conferring resistance to virus accumulation in potato.
AB  - Potato leafroll luteovirus (PLRV) movement through phloem of PLRV-resistant
      potato clones was examined in experiments in which stem pieces were grafted
      either between infected rootstocks and virus-free susceptible scions or between
      infected scions and virus-free susceptible rootstocks. These test plants
      permitted either upwards or downwards virus movement into the susceptible tissue.
      Resistant potato clones had either host gene-mediated resistance (H-MR) or
      transgene-mediated resistance (T-NR, conferred by transformation with the PLRV
      coat protein gene) to PLRV accumulation. The rate of PLRV movement was similar
      whether stem tissue was taken from H-MR, T-MR or susceptible potato clones. Virus
      movement through two graft unions began around 7 days after grafting and was
      generally complete by about 14 to 16 days. Virus movement occurred soon after
      acquiring functional phloem continuity across grafts as demonstrated by tracing
      with 6(5)-carboxyfluorescein, a phloem-mobile dye. Most of the delay in virus
      detection after grafting probably resulted from the time necessary to develop new
      phloem strands across graft unions; subsequent movement of PLRV was rapid
      suggesting a passive process. PLRV infection was largely excluded from external
      phloem bundles in stem tissue of clones with either H-MR or T-MR. This trait was
      less pronounced as tissue aged. The mechanism limiting PLRV invasion of external
      phloem bundles of the T-MR clones appears to be similar to that operating in the
      H-MR clones. Results are discussed in the context of a proposed model of PLRV
      movement.

PMID- 9010311
TI  - 3'-Terminal sequences of the RNA genomes of narcissus latent and Maclura mosaic
      viruses suggest that they represent a new genus of the Potyviridae.
AB  - The nucleotide sequences of part of the nuclear inclusion body b (NIb) gene, the
      complete coat protein gene and the 3' untranslated regions of narcissus latent
      virus (NLV) and Maclura mosaic virus (MacMV) were determined. Deduced amino acid
      sequences for the NIb and coat protein genes revealed that NLV and MacMV are
      closely related. Gel analysis and Western blotting of the coat proteins of NLV
      and MacMV from infected tissue or purified virus indicated that they have
      molecular masses of 39.5 kDa and 40 kDa (respectively), whereas estimates from
      deduced amino acid sequences suggested that they have molecular masses of 32.8
      kDa and 34.1 kDa. Comparison of the NIb and coat protein sequences with other
      viruses showed that NLV and MacMV have close affinities with viruses of the
      Potyviridae and suggests that they should form a new genus of the family.

PMID- 9010312
TI  - A nonoccluded reovirus of the olive fly, Dacus oleae.
AB  - We have isolated paraspherical viral particles, 60 nm in diameter, from adults of
      the olive fly (Dacus oleae) collected in Greece. The virus actively replicated in
      midgut epithelial cells and in advanced infections virions accumulated in
      microvilli. They were released in the gut lumen and were very abundant in fly
      faeces. The virions exhibited the salient features of reoviruses, with an
      external shell and an internal core with a tubular subunit protruding at each
      vertex of the icosahedron. The viral genome consisted of ten segments of double
      stranded RNA totalling 23.4 kbp. Based on its overall properties, this virus can
      be considered as a nonoccluded insect reovirus.

PMID- 9010313
TI  - A physical map of the Mamestra configurata nucleopolyhedrovirus genome and
      sequence analysis of the polyhedrin gene.
AB  - The genome structure of a nucleopolyhedrovirus (NPV) isolated from the bertha
      armyworm, Mamestra configurata Walker (Lepidoptera: Noctuidae) (MacoNPV) was
      analysed with six restriction endonucleases (REN): BamHI, EcoRI, HindIII, PstI,
      SmaI and Xhol. More than 70 MacoNPV REN fragments were cloned into plasmids pUC18
      and pBluescript SK(+). The physical map with 112 restriction sites for the above
      REN was constructed using double digests and Southern blot hybridization analysis
      of the MacoNPV DNA clones. The size of the DNA genome of the MacoNPV-90/2 isolate
      used for this study was estimated at 156 kbp based on REN fragment sizes. The
      position of the polyhedrin gene, which has by convention been used as the zero
      point of the REN maps of NPV, was determined by hybridizing the Autographa
      californica multicapsid nucleopolyhedrovirus HindIII-V fragment clone, which
      contains most of the polyhedrin gene, with genomic blots of MacoNPV. The cloned
      MacoNPV fragments identified as containing the polyhedrin gene were sequenced and
      an ORF coding for a 246 amino acid polypeptide with 98.7% sequence identity with
      Panolis flammea nucleopolyhedrovirus (PaflNPV) polyhedrin protein was identified.
      The putative polyhedrin gene sequence had 97.2% and 91.2% identity with the
      PaflNPV and Mamestra brassicae multicapsid nucleopolyhedrovirus polyhedrin gene
      sequences, respectively, and also contained an upstream region identical to the
      highly conserved 12 bp consensus sequence TGTAAGT-AATTT typical of NPV very late
      genes.

PMID- 9010314
TI  - Insecticidal activity of a recombinant baculovirus containing an antisense c-myc
      fragment.
AB  - Attempts to develop baculovirus-based insecticides by insertion of genes encoding
      enzyme inhibitors, neuropeptides or toxins have met with some success. However,
      it is often difficult to ensure correct processing or secretion of the encoded
      peptides. Here we tested a simpler strategy by insertion of an antisense fragment
      of a host gene to block translation of a protein essential for larval growth and
      development. We selected the c-myc gene for two main reasons: (i) its protein is
      known to be well conserved in evolution and to have multiple essential functions
      during development; and (ii) c-myc family genes have yet to be characterized in
      insects, thus blockage of essential genes by anti-sense transcripts from a strong
      virus promoter could provide a sensitive test for the existence of myc-like gene
      products. An appropriate fragment of the human c-myc gene was inserted downstream
      from the polyhedrin promoter of Autographa californica nucleopolyhedrovirus and
      tested in bioassays on Spodoptera frugiperda larvae. Western blot analysis with a
      human c-myc antibody revealed an endogenous protein band which bound specifically
      to these antibodies. This band disappeared more rapidly from cells infected with
      the antisense c-myc recombinant virus than from those infected with c-myc
      negative virus. Results of bioassays showed that the antisense construct stopped
      feeding as soon as the polyhedrin promoter-driven transcripts accumulated,
      followed shortly by death of the larvae. These results suggest that c-myc-like
      protein(s) exist in insects and that the antisense strategy is an effective
      approach to virus insecticide productions.

PMID- 9010315
TI  - Scrapie strains retain their distinctive characteristics following passages of
      homogenates from different brain regions and spleen.
AB  - The molecular basis of differences among scrapie strains is unknown. The prion
      theory posits that there are differences in the conformation of the host protease
      resistant protein (PrP) molecules and that these differences are responsible for
      scrapie strains. A corollary of this theory is that the origin of host PrP
      variation resides in different neuronal cell types. To assess this concept,
      preparations from three brain regions (cerebrum, cerebellum and olfactory bulb)
      and from spleen were passaged in C57BL mice by intracerebral injection. After
      three passages of three scrapie strains in this manner, homogenates of each brain
      region and spleen were tested for several of the characteristics that distinguish
      the three strains: (1) the rank order of incubation periods in C57BL mice, (2)
      induction of obesity in SJL mice and (3) comparative incubation periods in mice
      with three genotypes for the scrapie incubation period marker. Analysis revealed
      that virtually all of the criteria that distinguished the three strains prior to
      passages of the three brain regions and spleen were retained after this series of
      passages. This finding argues against cellular-based PrP differences providing a
      basis for strain specificity.

PMID- 9010316
TI  - Induction of cell-free, in vitro transcription by recombinant androgen receptor
      peptides.
AB  - An in vitro, cell-free transcription system, based on prostate-derived
      transcriptional machinery and very powerful androgen response elements (AREs),
      has been developed. Multiple (p(ARR3)LovTATA) AREs from the androgen-regulated
      probasin gene were linked to G-free cassettes and used in nuclear extracts
      prepared from prostate carcinoma cell lines (PC3 and LNCaP cells) to test
      specific induction of transcription by full-length AR and by glutathione-S
      transferase (GST)-fusion peptides in which the androgen receptor (AR) DNA-binding
      domain alone (AR524-649), or together with the ligand-binding domain (AR524-902),
      or a portion of the NH2-terminal domain (AR232-649) were incorporated. In the
      presence of AR, nuclear extracts from PC3 cells had greater activity in
      supporting transcription than those from LNCaP cells; and lower background
      activity than those from HeLa cells. All of the AR forms correctly initiated in
      vitro transcription of ARE-templates in an androgen-independent manner. The
      amount of specific, inducible transcript was dependent on the concentration of AR
      peptide present. AR524-902 was the most potent transactivator tested, with the
      maximal level of specific transcript over 900-fold higher than the minimal level.
      At all concentrations this peptide was three to four times more active than
      either AR524-649 or AR232-649. In conclusion, we have developed a very specific
      and sensitive cell-free transcription system for delineating trans-activational
      regions of the AR.

PMID- 9010317
TI  - Multiple splicing variants of the estrogen receptor are present in individual
      human breast tumors.
AB  - Transcript variants of the estrogen receptor (ER) were investigated in 109
      primary breast tumors using reverse transcription-polymerase chain reaction (RT
      PCR) and primers allowing analysis of each internal exon. A high incidence of
      different ER variants was observed, each individual tumor often manifesting
      multiple variants coexisting with corresponding wildtype (wt) ER. These variants,
      by sequence analysis confirmed to represent exon splicing deletions, included ER
      deltaE2 (found in 41% of the tumors examined), ER deltaE3 (74%), ER deltaE4
      (72%), ER deltaE5 (66%), and ER deltaE7 (88%). No evidence of transcripts lacking
      exon 6 was found, although a ER deltaE5,7 variant manifesting simultaneous
      deletion of exons 5 and 7 was observed. The presence of specific ER variants was
      not significantly correlated to the status of ER and progesterone receptor (PgR)
      protein expression, as assessed by routine analysis, although a trend towards a
      higher incidence of ER deltaE3 and increased expression of ER deltaE7 in ER+/PgR-
      tumors was observed, suggesting a dominant inhibitory effect on normal ER
      function to be involved. Moreover, ER deltaE4 was more common in ER+ tumors,
      possibly due to a cytoplasmic sequestring of this variant lacking a nuclear
      localization sequence. The presence of ER variants was not associated to
      clinicopathological variables, and equally frequent in tumors from patients
      having recurred or remained recurrence-free during adjuvant tamoxifen therapy. In
      conclusion, although ER splicing variants are abundant in breast cancer, the
      present study provides no evidence for a direct role of these ER variants in
      tumor development and tamoxifen resistance. It remains possible, however, that
      minor cell clones within the tumor, undetected by analysis of tumor homogenates,
      displaying extreme difference in content of ER variants, could be selected for
      during therapy or metastasis.

PMID- 9010318
TI  - Estrogen induction of TGF-alpha is mediated by an estrogen response element
      composed of two imperfect palindromes.
AB  - To investigate the molecular mechanisms underlying the two- to three-fold
      induction of human transforming growth factor-alpha (hTGF-alpha) mRNA and two- to
      five-fold induction of hTGF-alpha protein observed following estrogen treatment
      of hormone-responsive human breast cancer cell lines, the hTGF-alpha promoter was
      assayed for ERE-like sequences able to mediate estrogen induction of a
      heterologous gene. Transient co-transfection of a chloramphenicol acetyl
      transferase (CAT) construct consisting of either 1100 bp or 330 bp of hTGF-alpha
      promoter sequence and an estrogen receptor expression vector into either COS-7
      cells or hormonally responsive MCF-7 human breast cancer cells resulted in a two-
      to five-fold induction of CAT activity by estrogen. Although no consensus
      estrogen response element (ERE) exists in the hTGF-alpha promoter, a sequence
      consisting of two imperfect ERE palindromes separated by 20 bp is located at -200
      to -252. This sequence was inserted into a mouse mammary tumor virus (MMTV) based
      CAT construct and assayed for its ability to confer estrogen regulation of CAT
      expression to a heterologous promoter. Transient co-transfection of this
      construct with an estrogen receptor expression vector into either COS-7 cells or
      MCF-7 cells resulted in an average 30-fold estrogen induction of CAT activity.
      Gel shift assays with human recombinant estrogen receptor (ER) and 32P-labelled
      fragments revealed that the ER could specifically bind to this sequence. These
      results indicate that this 53 bp sequence can function as an ERE, and is likely
      to be responsible for the observed induction of TGF-alpha message and protein in
      response to estrogen. These data also indicate that the level of estrogen
      inducibility mediated by this element may be positively or negatively modulated
      by interaction or competition with other transcription factors.

PMID- 9010319
TI  - Triiodothyronine mimics the effects of estrogen in breast cancer cell lines.
AB  - MCF-7 (estrogen receptor positive--ER+) and MDA-MB-231 (estrogen receptor
      negative--ER-) are human breast cancer cell lines which express functional
      thyroid hormone receptors (c-erb A alpha1 and c-erb beta1) as indicated by
      stimulation of mitochondrial alpha-glycerophosphate dehydrogenase. In MCF-7,
      mimicking E2, T3 stimulated growth in a dose-dependent (10(10) M - 10(-8) M)
      manner, induced the expression of progesterone receptor and growth factor
      TGFalpha mRNAs and inhibited that of TGFbeta mRNA; T3 also increased progesterone
      binding and LDH5 isozyme activities. None of these effects were observed in (ER-)
      MDA-MB-231 cells. 10(-6) M tamoxifen (TAM) reverted growth stimulation,
      suppressed progesterone receptor and TGFalpha mRNA induction and restored TGFbeta
      mRNA to control levels in T3-treated MCF-7 cells. That T3 is acting in MCF-7
      cells via its binding to ER is suggested by the immunoprecipitation of pre-bound
      125I-T3 from MCF-7 nuclear extracts by an ER-specific monoclonal antibody and by
      the displacement of 3H-estradiol binding to ER by radioinert T3.

PMID- 9010320
TI  - Studies into aromatase activity associated with fetal allantochorionic and
      maternal endometrial tissues of equine placenta. Identification of metabolites by
      gas chromatography mass spectrometry.
AB  - Maternal endometrial and fetal allantochorionic tissues were separated manually
      from the placentae of seven healthy thoroughbred and three pony mares, ranging in
      gestational age from 100 to 318 days. The homogeneity of subcellular fractions
      prepared from these tissues was assessed initially using the marker enzymes,
      succinate dehydrogenase, NADPH cytochrome C reductase and lactate dehydrogenase
      for the mitochondrial, microsomal and cytosolic fractions, respectively. Light
      microscopy and histochemical analysis demonstrated that the separated fetal
      allantochorionic membrane, which is made up of allantoic and chorionic epithelia,
      contained no significant contamination of maternal tissues. The maternal
      endometrium, however, was found to contain appreciable amounts of fetal chorion
      torn off during the separation process. Tissue homogenates and subcellular
      fractions were incubated with testosterone together with [4-(14)C] and [(2)H5 or
      (2)H3] labelled analogues in either an NADPH (1 mM) or a NADPH-regenerating
      environment; control experiments (without additional cofactor) were also
      performed. After extraction of the tissue homogenates, neutral and phenolic
      (oestrogen) unconjugated steroids were separated by column chromatography.
      Radiolabelled studies revealed that in allantochorionic tissue incubations 67-77%
      of testosterone was converted to oestrogenic material, subcellular fractionation
      indicating that oestrogen production was largely confined to the microsomal
      fraction and time-course studies showing that the rate of formation appeared to
      be linear up to 90 min. In contrast, only 5-25% conversion occurred using
      maternal endometrial tissues, which could be accounted for by the contaminating
      presence of fetal chorion. No oestrogen production was detected in control
      incubations. These radiolabelled studies demonstrate that aromatase activity is
      located on the fetal allantochorionic surface and, together with the
      histochemical data, further delineate this activity to the chorion in mature
      equine placenta. Gas chromatographic-mass spectrometric (GC-MS) analysis of the
      phenolic extracts from allantochorionic tissue homogenate incubations indicated
      the presence of substrate-derived oestradiol-17beta (E2), 6-oxo-oestradiol-17beta
      (6-oxo-E2) and 6beta-hydroxyoestradiol-17beta (6beta-OH-E2). Whereas all three
      oestrogens were identified as metabolites from testosterone in incubations
      performed using allantochorionic tissue homogenates and post-mitochondrial
      suspensions (PMS), only E2 was identified from incubations performed using
      microsomal fractions prepared from this tissue. We conclude that both the
      microsomal and cytosol fractions are required for the conversion of E2 to the 6
      oxygenated species in vitro. Using stable isotope-labelled substrates and GC-MS
      analysis the mechanism of formation of these metabolites from these in vitro
      incubation studies may be inferred. GC-MS analysis of the neutral extracts from
      allantochorionic tissue homogenate incubations confirmed the presence of small
      quantities of substrate-derived 5(10)-oestrenediols. No substrate-derived 5(10)
      oestrene-3,17-diols were detected in extracts from microsomal preparations
      incubated in the absence of cytosol. These data suggest that demethylation of C19
      steroids to produce C18 neutral steroids may require the synergistic action of
      enzymic activities that appear to reside both in the microsomal and cytosolic
      fractions of equine allantochorionic tissues.

PMID- 9010321
TI  - Sex hormone binding globulin mRNA in human breast cancer: detection in cell lines
      and tumor samples.
AB  - Sex hormone binding globulin (SHBG) is a high affinity binding protein for
      estrogens and androgens. SHBG has been found in breast tissue and cell lines
      through immunostaining. The goal of this series of experiments was to determine
      whether mRNA for SHBG is expressed in breast cancer cell lines and tumor tissue.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect SHBG
      and beta-2 microglobulin (control for tissue extractions). Three breast cancer
      cell lines, ZR-75-1, MCF-7, and MDA-MB-231 and 56 breast tissue samples were
      collected and analysed for SHBG mRNA expression. mRNA was successfully extracted
      from 30 of these breast tissue samples. SHBG mRNA was detected in ZR-75-1, MCF-7
      and MDA-MB-231 cells, and in 11 of the breast tissue samples. Two PCR products
      were routinely amplified from the breast cancer cell line RNA, one at
      approximately 500 bp and another at approximately 300 bp. The DNA sequence of the
      300 bp PCR produce was consistent with alternate splicing of the SHBG mRNA, where
      exon 7 is deleted, and is accompanied by a point deletion at the beginning of
      exon 8. SHBG protein production from the three breast cancer cell lines was
      detected by immunoprecipitation using an affinity purified SHBG antibody. SHBG
      mRNA was found in 11 of 30 samples of breast tissue. Some samples expressed only
      the 500 bp or the 300 bp PCR product, whereas others expressed both PCR products.
      The presence of SHBG mRNA in these samples was not associated with either the
      presence or absence of steroid receptors. SHBG mRNA is thus expressed in breast
      cancer cell lines, and in some breast tissue samples.

PMID- 9010322
TI  - Optimization of a classical aromatase activity assay and application in normal,
      adenomatous and malignant breast parenchyma.
AB  - The tritium water release assay, originally described for the analysis of
      aromatase activity in placental tissue, was used to estimate aromatase activity
      in breast tissue samples. The lower activity in this tissue necessitates longer
      incubation times and thus optimization of the assay conditions. To prevent
      oxidative and proteolytic inactivation of aromatase, dithiothreitol and albumin
      were added to the incubation mixture. Extra NADPH, cofactor in the aromatase
      reaction, also improved reaction rate in placental incubations, but after
      approximately 120 min activity rapidly decreased. Inhibitors gradually produced
      during the incubation could explain this phenomenon. Quantitative gas
      chromatography-mass spectrometry (GC-MS) analyses of testosterone, oestradiol,
      oestrone and androstenedione after incubation with non-labelled androstenedione
      proved that a substantial amount of the substrate is converted into testosterone.
      Qualitative GC-MS steroid profiling of the incubation mixture demonstrated the
      presence of hydroxylated oestradiol and hydroxylated testosterone, produced
      during incubation, which could have caused partial aromatase inhibition. The
      adjusted assay was used to analyse 84 breast tissue samples, histologically
      classified as normal, adenoma or carcinoma. Aromatase activity was found in 56%
      of all samples and ranged from 0.6 to 26 pmol oestrogen/g protein per hour.
      Aromatase positivity was found in 80% of the normal samples, 56% of the adenoma
      samples and 48% of the carcinoma samples. Although carcinoma samples were less
      often aromatase positive than normal tissue samples (chi2 = 4.80; P < 0.050)
      there was no difference in absolute aromatase activity. Because no less than
      approximately 50% of the carcinomas contained aromatase activity and because of
      the non-routine character of the assay we conclude that it is justified to start
      aromatase inhibition therapy without previous knowledge of the aromatase status.

PMID- 9010323
TI  - Effects of androgen on brain and pituitary androgen receptors and LH secretion of
      male guinea pigs.
AB  - To study the tissue-specific control of androgen receptors by circulating
      androgens, guinea pigs were castrated or castrated and treated with crystalline
      testosterone propionate. Levels of serum androgens and LH were measured and brain
      and peripheral tissues were collected for determination of androgen receptor
      levels under differing androgen states. We found that circulating androgen levels
      changed rapidly following castration or treatment with exogenous androgen. LH
      secretion was coupled to circulating androgens; high levels of androgen quickly
      suppressed LH secretion, whereas LH levels did not rise significantly above
      intact levels until 7 days following castration. Androgen receptor levels were
      effected by circulating androgens. Cytosolic androgen receptors (ARc) increased
      significantly in the preoptic area (POA), septum, anterior pituitary, prostate
      and seminal vesicle following castration, whereas nuclear androgen receptors
      (ARn) decreased significantly in the POA, septum, medial basal hypothalamus
      (MBH), amygdala, parietal cortex, pituitary, prostate and seminal vesicle.
      Exogenous androgens, which increased serum steroid levels significantly above
      that in intact animals, decreased ARc below control levels in MBH, amygdala,
      pituitary and seminal vesicle. High circulating androgens increased ARn above
      intact levels in the MBH, pituitary and prostate. It thus appears that
      circulating androgens regulate LH secretion and have profound, but tissue
      specific effects on androgen receptors in the guinea pig.

PMID- 9010324
TI  - Effects of corticosteroids on parameters related to Na+ transport by amphibian
      renal distal cells (A6) in culture.
AB  - The present study addresses the effects of the hormones aldosterone and
      corticosterone, as well as those of dexamethasone, on cultured renal amphibian
      cells, focusing on parameters thought relevant for the further understanding of
      the regulation by these steroids of Na+ reabsorption along the renal tubule.
      Exposure to these steroids of A6 cell monolayers grown on a permeable support
      produced a motor, dose-dependent, increase in Na+ transport, reflected by the
      short-circuit current, Isc. (Na+ + K+)-ATPase activity and ouabain binding, both
      of which are linearly correlated with Isc in control tissue, also increased
      significantly after steroid treatment. Dexamethasone was consistently more active
      than corticosterone and aldosterone on the parameters studied. The increase in
      Isc and (Na+ + K+)-ATPase activity elicited by dexamethasone could be blocked by
      the glucocorticoid antagonist RU 486, whereas it was only slightly reduced by the
      mineralocorticoid antagonist, spironolactone. In contrast, the latter strikingly
      reduced the effects of aldosterone on these parameters, unlike RU 486.
      Furthermore, the effects of large doses of dexamethasone and aldosterone combined
      were not additive. Taken together, the data presented appear compatible with the
      view that the effects of aldosterone on Na+ transport by A6 cells are mediated by
      a fraction of the receptors involved in the response to dexamethasone; they
      furthermore raise the question of whether, in lower vertebrates, it is relevant
      to make a distinction between "gluco" and "mineralo"corticoids.

PMID- 9010325
TI  - Effects of dexamethasone on (Na+ + K+)-ATPase and other parameters related to
      transepithelial Na+ transport by amphibian renal distal cells (A6) in culture.
AB  - In the present report, the effects exerted by dexamethasone on transepithelial,
      electrogenic Na+ transport across A6 cell monolayers grown on permeable support
      were further characterized in terms of time course and relationship to the rate
      of Na+ transport; furthermore this agonist was compared to vasopressin and
      insulin. (Na+ + K+)-ATPase activity and density of ouabain binding sites were
      measured in cell homogenates and on dispersed cells, respectively, after
      documenting transepithelial electrical parameters of the preparations. Na+
      transport, measured by short-circuit current (Isc), was increased almost five
      fold (control: 6.7 +/- 0.1 microA/cm2) after incubation with 10(-7) M
      dexamethasone for 24 h. Stimulation of Na+ transport rate was associated with a
      2.3-fold increase in (Na+ + K+)-ATPase activity (control: 5.5 +/- 0.3 micromol
      Pi/mg prot.h), and ouabain binding site density almost doubled (control: 236 +/-
      10 fmol/10(6) cells). The steroid acted on the Na+ pump of A6 cells in the
      absence of transepithelial Na+ transport, with intracellular Na+ ion activity
      playing an additional role in terms of cell Na+ pump numbers. In the case of
      insulin and vasopressin, in contrast, there was no effect on Na+ pump activity in
      the absence of Na+ transport by A6 cell monolayers. The increase in (Na+ + K+)
      ATPase activity observed in A6 cell monolayers treated with dexamethasone is
      therefore a result of the direct induction of Na+ pump biosynthesis, with an
      almost proportional insertion of operational Na+ pumps into the basolateral
      membrane. In contrast, increased Na+ entry at the apical cell pole appears to be
      essential for insulin and vasopressin action on A6 cell Na+ pump.

PMID- 9010326
TI  - Occurrence of steroidogenic enzymes in the bovine mammary gland at different
      functional stages.
AB  - After the incubation of minced mammary tissues from non-lactating/non-pregnant
      (NL/NP), nonlactating/pregnant (NL/P), fully lactating (FL) and late-lactating
      (LL) cows with [14C]-labelled pregnenolone or progesterone and
      dehydroepiandrosterone (DHEA), the following metabolites were identified at all
      stages: 20alpha-dihydropregnenolone, progesterone (from pregnenolone), 5alpha
      pregnanedione, 5alpha-pregnan-3beta-ol-20-one, 20alpha- and 20beta
      dihydroprogesterone (from progesterone), 5-androstene-3beta,17beta-diol, 5alpha
      androstanedione, 5alpha-androstan-3beta-ol-17-one, androstenedione, testosterone
      and DHEA acyl ester (from DHEA). These products indicate the occurrence of 3beta
      hydroxysteroid dehydrogenase/delta5-delta4 isomerase, 17beta-hydroxysteroid
      oxidoreductase (17beta-HOR), 20alpha- and 20beta-hydroxysteroid dehydrogenases,
      steroid 5alpha-reductase and acyl transferase activities. Incubation of mammary
      tissue homogenates with [1,2,6,7-(3)H]androstenedione and testosterone confirmed
      the presence of a 17beta-HOR acting prevalently in a reductive way but failed to
      show evidence of any aromatase activity beyond background level. When total RNA
      from mammary tissues of NL/NP and LL cows was reverse-transcribed and amplified
      by polymerase chain reaction (PCR) with three sets of primers specific for bovine
      P450scc, P450c17 and P450arom cDNAs, no fragment of the expected size could be
      detected on gel. Southern analysis with corresponding digoxigenin-labelled
      ovarian probes, however, gave a positive signal for P450arom cDNA in five out of
      eight samples of LL mammary tissue. These data indicate that the bovine mammary
      gland has very limited steroidogenic capabilities that are essentially compatible
      with the terminal activation of circulating steroids from steroidogenic
      endocrines. It is uncertain, however, whether this conclusion applies to
      anestrous or ovariectomized lactating cows as well.

PMID- 9010327
TI  - Response-specific antiestrogen resistance in a newly characterized MCF-7 human
      breast cancer cell line resulting from long-term exposure to trans
      hydroxytamoxifen.
AB  - To understand better the antiestrogen-resistant phenotype that frequently
      develops in breast cancer patients receiving tamoxifen, we cultured MCF-7 breast
      cancer cells long-term (>1 yr) in the presence of the antiestrogen trans
      hydroxytamoxifen (TOT) to generate a subline refractory to the growth-suppressive
      effects of TOT. This subline (designated MCF/TOT) showed growth stimulation,
      rather than inhibition, with TOT and diminished growth stimulation with estradiol
      (E2), yet remained as sensitive as the parental cells to growth suppression by
      another antiestrogen, ICI 164,384. Estrogen receptor (ER) levels were maintained
      at 40% of that in parent MCF-7 cells, but MCF/TOT cells failed to show an
      increase in progesterone receptor content in response to E2 or TOT treatment. In
      contrast, the MCF/TOT subline behaved like parental cells in terms of E2 and TOT
      regulation of ER and pS2 expression and transactivation of a transiently
      transfected estrogen-responsive gene construct. DNA sequencing of the hormone
      binding domain of the ER from both MCF-7 and MCF/TOT cells confirmed the presence
      of wild-type ER and exon 5 and exon 7 deletion splice variants, but showed no
      point mutations. Compared to the parental cells, the MCF/TOT subline showed
      reduced sensitivity to the growth-suppressive effects of retinoic acid and
      complete resistance to exogenous TGF-beta1. The altered growth responsiveness of
      MCF/TOT cells to TOT and TGF-beta1 was partly to fully reversible following TOT
      withdrawal for 16 weeks. Our findings underscore the fact that antiestrogen
      resistance is response-specific; that loss of growth suppression by TOT appears
      to be due to the acquisition of weak growth stimulation; and that resistance to
      TOT does not mean global resistance to other more pure antiestrogens such as ICI
      164,384, implying that these antiestrogens must act by somewhat different
      mechanisms. The association of reduced retinoic acid responsiveness and
      insensitivity to exogenous TGF-beta with antiestrogen growth resistance in these
      cells supports the increasing evidence for interrelationships among cell
      regulatory pathways utilized by these three growth-suppressive agents in breast
      cancer cells. In addition, our findings indicate that one mechanism of
      antiestrogen resistance, as seen in MCF/TOT cells, may involve alterations in
      growth factor and other hormonal pathways that affect the ER response pathway.

PMID- 9010328
TI  - Zebra finch estrogen receptor cDNA: cloning and mRNA expression.
AB  - In zebra finches, estrogen is a potent hormone that masculinizes the neural
      circuitry controlling song during development and activates song in adulthood.
      However, previous studies have reported conflicting patterns of estrogen receptor
      (ER) expression in the song control regions. To obtain additional information
      about the distribution of ER in the zebra finch brain, a cDNA encoding an
      estrogen receptor was isolated from a zebra finch hypothalamic-preoptic area cDNA
      library. The 2792 bp insert contains a 1764 bp open reading frame with 5' and 3'
      untranslated regions of 132 bp and 896 bp, respectively. The deduced polypeptide
      is 589 amino acids in length and is highly homologous to the estrogen receptors
      of chicken (97%), rat (79%), mouse (79%), human (78%), Xenopus laevis (76%) and
      trout (49%). Northern blot analysis revealed three ER mRNAs expressed
      differentially in ovary, oviduct and telencephalon. The smallest transcript, 4.1
      kb, was expressed in all three tissues, whereas larger mRNAs were expressed in
      ovary (7.6 kb) and oviduct (8.1 kb). In situ hybridization histochemistry
      revealed strong labelling in the infundibular region of the hypothalamus,
      preoptic area, and medial caudal neostriatum. Few or no labelled cells were found
      in the song control nuclei (HVC, RA, MAN or Area X). These results are consistent
      with previous studies that have shown ER protein and binding in hypothalamic and
      preoptic area and a lack of ER in most regions that control song production.

PMID- 9010329
TI  - Human serum albumin shares the properties of estrocolyone-I, the inhibitor of the
      proliferation of estrogen-target cells.
AB  - The control of cell proliferation by estrogens was examined under the premises of
      the indirect-negative hypothesis, which states that estradiol cancels the
      proliferative inhibition exerted by a serum-borne protein on estrogen-target
      cells. Fractionation protocols resulted in the co-elution of the inhibitory
      activity with serum albumin. Removal of human albumin (HA) from charcoal-dextran
      stripped serum by hexyl-S agarose chromatography resulted in a preparation
      lacking inhibitory effect. HA inhibited the proliferation of human estrogen
      target MCF-7 cells. Human non-estrogen-target MDA-MB231 cells were impervious to
      the effect of HA. MCF-7 cells were exposed to recombinant human albumin (rHA) and
      to its rDomain I and rDomains I + II. Inhibition of proliferation was maximal
      with rHA and with rDomains I + II; rDomain I was less inhibitory. The inhibitory
      effect of albumin was cell type and protein specific. Only estrogens cancelled
      the albumin inhibition; recombinant growth factors and other hormones were
      ineffective. These data suggest that: (a) albumin or a portion of it (most likely
      within Domains I and II) is the specific inhibitory signal for the proliferation
      of human estrogen-target, serum-sensitive cells; (b) estrogens specifically
      cancel this inhibition; (c) inhibitory signals prevail over putative growth
      factors; and (d) the default state in these cells is proliferation.

PMID- 9010330
TI  - Environmental estrogens: effects on cholesterol lowering and bone in the
      ovariectomized rat.
AB  - Representative non-steroidal estrogens, from common environmental sources such as
      plants, pesticides, surfactants, plastics, and animal health products,
      demonstrated an ability to lower serum cholesterol and prevent bone loss.
      Specifically, select environmental estrogens (coumestrol, genistein,
      methoxychlor, bisphenol A, and zeranol) effectively lowered total serum
      cholesterol in an estrogen-dependent animal model, the ovariectomized rat. Of
      these entities, coumestrol, methoxychlor, and zeranol prevented ovariectomy
      induced bone loss. In an in vitro environment, these compounds competed with
      17beta-estradiol for estrogen receptor binding and stimulated cell proliferation
      in a human breast cancer cell line (MCF-7). In addition to their well-documented
      effects on reproductive tissue, various environmental estrogens can dramatically
      affect non-reproductive parameters such as cholesterol lowering and bone
      metabolism.

PMID- 9010331
TI  - Aromatase gene expression and its exon I usage in human breast tumors. Detection
      of aromatase messenger RNA by reverse transcription-polymerase chain reaction.
AB  - The expression of aromatase in human breast tumors has been studied by the
      reverse-transcription polymerase chain reaction (RT-PCR) method on 70 breast
      tissue specimens. An RT-PCR analysis using two oligonucleotide primers derived
      from the exon II of the human aromatase gene revealed that aromatase mRNA was
      detected in all but three tissue specimens. Furthermore, primer-directed RT-PCR
      was performed to determine the exon I usage in aromatase mRNA in these breast
      tumor specimens. The analysis has revealed that exons I.3 and PII are the two
      major exon Is present in aromatase mRNA isolated from breast tumors, suggesting
      that promoters I.3 and II are the major promoters driving aromatase expression in
      breast cancer and surrounding adipose stromal cells. The RT-PCR analysis also
      detected two products, I.3A (334 bp in length) and I.3B (222 bp in length), when
      it was carried out using a primer derived from exon I.3 and a reverse primer
      derived from exon II. The nucleotide sequences of these products have been
      determined and indicate that I.3A contains a region which was previously thought
      to be an intron. In addition, RT-PCR analyses of RNA isolated from eight pairs of
      breast tumor and neighboring normal tissue specimens were performed to evaluate
      the exon I usage and the distribution of I.3A- and I.3B-containing aromatase RNA
      messages in breast tumor and neighboring normal tissues. The results suggest that
      I.3B- and I.3A-containing messages are mainly present in breast tumor and
      neighboring normal tissues, respectively. Finally, the exon I/promoter usage for
      aromatase expression in eight cell lines (skin fibroblast, MCF-7, MDA-MB-231, T
      47D, SK-BR-3, JAR, OVCAR-3, and human adipose stromal cells) was examined by
      primer-directed RT-PCR analyses. These studies provide a basis for further
      evaluation of the control mechanism of aromatase expression and estrogen
      biosynthesis in breast tumors.

PMID- 9010332
TI  - Opioids regulate cell proliferation in the developing rat uterus: effects during
      the period of sexual maturation.
AB  - The present studies demonstrate, for the first time, that the rate of DNA
      synthesis in rat uterus of 21-32 days of age is inhibited by opioid peptides [D
      Met2, Pro5]enkephalinamide. At around the time of vaginal opening (approximately
      33 days) the opioids failed to act. High-affinity nuclear [3H]naloxone binding
      sites with linear Scatchard plots were detected in the uteri during the opioid
      sensitive periods of DNA synthesis. Characteristics of these binding sites and
      the opioid sensitivity of uterine DNA synthesis are dependent on the age of the
      animals, the level of circulatory oestradiol and/or the maturity of the nuclear
      oestrogen receptor system.

PMID- 9010333
TI  - Endometrial effects of RU486 in primates--antiproliferative action despite signs
      of estrogen action and increased cyclin-B expression.
AB  - Continuous antiprogestin administration to hormone replaced, castrate monkeys
      inhibits estrogen-induced endometrial proliferation through mechanisms which
      remains unclear. To elucidate the molecular mechanisms of RU486-induced
      endometrial suppression, we treated six intact female cynomolgus monkeys on cycle
      days 2-22 sequentially with placebo, RU486 (1 mg/kg/day) and levonorgestrel (LNG)
      (2 microg/kg/day) intramuscularly (i.m.), with uterine wedge sections and
      endometrial biopsies collected on day 22 of each cycle. The uterine sections were
      evaluated for morphology, mitosis and proliferating cell nuclear antigen (PCNA)
      immunohistochemistry. Changes in the mRNA levels of ER, PR, cyclin-B and tumour
      suppressor gene p21 were assessed using co-amplification with beta-actin by
      reverse transcriptase-polymerase chain reaction (RT-PCR). Administration of RU486
      uniformly resulted in characteristic suppression of endometrium with few mitosis,
      dense stroma and simple glands, whereas the effects of LNG were less uniform.
      Following RU486 administration, the levels of endometrial ER and PR mRNA were
      comparable to proliferative phase endometrium, and significantly higher than
      those seen in the secretory endometrium, indicating that some of the biological
      actions of E2 were not inhibited during RU486 treatment. Despite scarce mitosis,
      PCNA was readily detectable in all samples. Curiously, in comparison to secretory
      phase controls, the levels of cyclin-B, but not p21, mRNA were markedly increased
      following RU486. The effects of LNG on the levels of these mRNA species varied,
      with mean levels falling between those of the secretory phase controls, and RU486
      treated specimens. The increase in cyclin-B mRNA and lack of mitosis suggests
      that anti-proliferative actions of RU486 in the primate endometrium might be
      associated with a cell-cycle block at the G2-M interphase. Whether mechanisms
      similar to these are associated with the beneficial clinical effects of RU486
      seen in the treatment of various hormone dependent maladies remains to be
      determined.

PMID- 9010334
TI  - Aromatase activity and CYP19 gene expression in breast cancers.
AB  - The aromatase enzyme complex is responsible for the conversion of C19 androgens
      to oestrogens. Aromatase expression in oestrogen-responsive breast cancers may be
      an important mechanism of autocrine regulation in tumour growth. To evaluate
      whether aromatase cytochrome P450 (P450arom) transcript levels within breast
      tumours were correlated to the enzyme activity, a specific competitive reverse
      transcription-polymerase chain reaction (RT-PCR) was developed. In this reaction,
      a 32 base-deleted complementary RNA was used as internal standard. In vitro
      aromatase activity was measured by either the tritium release assay or
      characterization of oestrogen fractions. Results indicate that there is a
      positive correlation between P450arom transcript levels and enzyme activity, but
      the relationship does not reach statistical significance. Therefore, whereas
      aromatase mRNA quantification may be an option by which to monitor the potential
      of tumour to synthesize oestrogens, it will not accurately reflect enzyme
      activity in a minority of tumours. Preliminary evidence was obtained in a tumour
      with low enzyme activity and a high P450arom transcript level for the presence of
      an endogenous aromatase inhibitor. This study highlights the necessity to
      characterize factors involved in the regulation of aromatase activity in such
      tumours.

PMID- 9010335
TI  - 5alpha-reductase 1 and 2 expression and activity in human ovarian follicles,
      stroma and corpus luteum as compared to neonatal foreskin.
AB  - 5alpha-Reductase is the steroidogenic enzyme which reduces testosterone to 5alpha
      dihydrotestosterone. In the human two different enzymes have been described,
      5alpha-reductase 1 and 2. The present investigations were undertaken to determine
      whether 5alpha-reductase 1 and 2 were expressed in the human ovary, and to
      determine the relative activity of the two enzymes in various ovarian tissues.
      The ovary apparently expressed mRNA for only 5alpha-reductase 1, whereas the
      foreskin expressed both 5alpha-reductase 1 and 2. We compared the 5alpha
      reductase activity at both pH 5.5 (optimum for 5alpha-reductase 2 activity) and
      8.0 (optimum for 5alpha-reductase 1 activity). 5alpha-reductase activity of
      foreskin at pH 5.5 was 3900 times higher than small follicles, 1500 times higher
      than ovarian stroma, and 240 times higher than corpora lutea (all P < 0.01).
      5alpha-reductase activity of corpora lutea at pH 5.5 was 17-fold higher than that
      of follicles (P < 0.01) and 6.5-fold higher than that of ovarian stroma (P <
      0.05). 5alpha-Reductase activity of foreskin at pH 8.0 was 93 times higher than
      small follicles, 51 times higher than corpora lutea, and 170 times higher than
      ovarian stroma (all P < 0.01). The ratio of 5alpha-reductase activity at pH 5.5
      to that at pH 8.0 was higher in foreskin than in corpus luteum (P < 0.05),
      ovarian stroma (P < 0.01), or ovarian follicles (P < 0.01). The ratio was lower
      in ovarian follicles than in stroma or corpus luteum (both P < 0.05).

PMID- 9010336
TI  - Purification and characterization of 17beta-hydroxysteroid dehydrogenase from the
      filamentous fungus Cochliobolus lunatus.
AB  - 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) from the filamentous fungus
      Cochliobolus lunatus was purified in three steps, yielding a protein of an
      apparent molecular mass of 28 kDa. According to the obtained experimental data,
      the native form of the enzyme could be a dimer (60 kDa) and/or a tetramer (120
      kDa). The enzyme was found to catalyse preferentially the reduction of steroid
      substrates using NADPH as an electron donor. Both androgens and estrogens are
      substrates for 17beta-HSD. Kinetic studies revealed the equilibrium ordered
      kinetic mechanism with NADPH as the first ligand to be bound to the enzyme
      followed by the addition of the substrate androstenedione. The purification and
      characterization of 17beta-HSD from Cochliobolus lunatus represents a step
      towards the elucidation of the role of this enzyme in fungal metabolism.

PMID- 9010337
TI  - Uterine estradiol and progesterone receptor concentration, activities of certain
      antioxidant enzymes and dehydrogenases and histoarchitecture in relation to time
      of secretion of nidatory estrogen and high endometrial sensitivity in rat.
AB  - Alterations in uterine nuclear and cytosolic estradiol (ER) and progesterone (PR)
      receptor concentration, activities of superoxide dismutase (SOD), peroxidase
      (POD), catalase (CAT), glucose-6-phosphate dehydrogenase (G-6-PDH) and lactate
      dehydrogenase (LDH), surface and transmission electron microscopy and histology
      in relation to the time of secretion of nidatory estrogen and the onset of
      endometrial sensitivity in the rat were investigated. A significant increase in
      plasma estradiol (E2) concentration in control rats was observed at 22.00 h on
      day 4 post-coitum, whereas progesterone (P) concentration increased at 17.00 h on
      day 4 and was maintained until 17.00 h on day 5. The period of high endometrial
      sensitivity (10.00 h on day 5) was characterized by elevated uterine cytosolic ER
      and nuclear and cytosolic PR concentration and POD activity, low columnar luminal
      epithelium with undulating surface and intercellular membranes, covered with
      short microvilli and pinopods, and containing numerous electron-transparent
      apical vesicles, mitochondria, polyribosomes, rough (RER) and smooth (SER)
      endoplasmic reticulum, well developed Golgi, few lysosomes and lipid droplets and
      loose edematous antimesometrial stroma. Inhibition in endometrial sensitivity by
      post-coital centchroman was associated with a marked depletion in uterine
      cytosolic ER and an increase in nuclear ER concentration, a decrease in POD and G
      6-PDH activities, compact fibroblastic stroma, an increase in luminal epithelial
      cell height with decreased RER, SER, polyribosomes, Golgi, straightening of
      intercellular membranes, reduced surface undulations and absence of pinopods.
      Electron-transparent vesicles appeared flattened and clumped in the apical
      portion of cells, tight junctions were more prominent and lipid droplets were
      translucent. Nuclear and cytosolic PR and the pattern of secretion or plasma E2
      and P remained unaffected. CAT, SOD and LDH activities, although high throughout
      pre-implantation, did not vary in relation to the secretion of nidatory estrogen,
      endometrial sensitivity or centchroman treatment.

PMID- 9010338
TI  - Anabolic steroids and lymphocyte function in sedentary and exercise-trained rats.
AB  - The effects of the administration of suprapharmacological doses of anabolic
      steroids (AASs) on the immune system were examined in sedentary and exercise
      trained rats by testing mobility and proliferative response in cultures of thymus
      and spleen-derived lymphocytes. Male Wistar rats were exercise-trained following
      two programmes of treadmill running of 3 months duration, differing in intensity,
      in the absence of treatment or with simultaneous i.m. administration of a
      suprapharmacological dose (10 mg/kg/week) of nandrolone decanoate (ND) or
      stanozolol (ST) during the past two months. At this dose ND reduced body weight
      gain, promoted a redistribution of immune cells from thymus to spleen, impaired
      lymphocyte mobility and inhibited the mitogen-induced proliferative response
      (about 90% inhibition for thymus-derived cells). Stanozolol (ST) treatment was
      without effect on body weight gain, but it also induced a redistribution of
      lymphocytes and modified the in vitro lymphocyte activity, although less severely
      than ND. Application of the high-intensity training programme reduced lymphocyte
      mobility and proliferation in vitro and a simultaneous treatment with anabolic
      steroids further impaired some of the immune cell responses. Application of the
      endurance-directed training programme, however, did not reduce mobility or
      mitogen-induced proliferation of lymphocytes, and normalized the activity of
      these cells in anabolic steroid-treated rats. So, endurance exercise, contrary to
      high-intensity training, could counteract the apparent negative effects of high
      doses of androgens on lymphocyte function.

PMID- 9010339
TI  - Membrane binding sites and non-genomic effects of estrogen in cultured human pre
      osteoclastic cells.
AB  - Besides functional estrogen receptors, the presence of signalling cell surface
      binding sites for 17beta-estradiol (17betaE2) has been reported in osteoblast-
      and osteoclast-like cells, suggesting that 17betaE2 may influence bone
      remodelling by a dual mechanism of action: to affect gene expression mediated by
      the nuclear activity of the steroid-receptor complex, and to initiate rapid
      responses triggered by a signal-generating receptor on the cell surface.
      Recently, we demonstrated that the human pre-osteoclastic cell line FLG 29.1
      bears functional estrogen receptors. In this study we examined FLG 29.1 cells for
      the presence of cell surface binding sites for 17betaE2, and whether 17betaE2
      could elicit cell signalling. Using a cell-impermeant and fluorescent estrogen
      conjugate, 17beta-estradiol-6-carboxymethyloxime-bovine serum albumin-fluorescein
      isothiocyanate, we demonstrated the presence of specific plasma membrane binding
      sites for 17betaE2. Stimulation of FLG 29.1 cells with low (1 nM) and high (1
      microM) doses of 17betaE2 induced a prompt and significant (P < 0.05) increase of
      cellular pH, as measured in single cells using an image analysis system. In
      addition, both cAMP and cGMP were significantly increased by 17betaE2 with a dose
      dependent response. Finally, a rapid increase of intracellular calcium ion
      concentration [Ca2+] was also induced by 1 nM 17betaE2, as measured in single
      cells using an image analysis system. Our findings strongly suggest a non-genomic
      action of 17betaE2 on osteoclast precursors.

PMID- 9010340
TI  - Progestins: present and future.

PMID- 9010341
TI  - Bacterial 3alpha-hydroxysteroid dehydrogenase is homologous to a fusion of
      bacterial ribosomal L10 and L7/12 genes.
AB  - 3alpha-Hydroxysteroid dehydrogenase catalyzes the reversible oxidation of 3alpha
      hydroxyl groups of the steroid nucleus. Sequence analysis reveals that this
      enzyme is homologous to ribosomal proteins L10 and L7/12. The alignment suggests
      that 3alpha-hydroxysteroid dehydrogenase is formed by a fusion of the two
      ribosomal proteins.

PMID- 9010343
TI  - Vitamin D receptor interactions with the murine osteopontin response element.
AB  - The nature of the DNA binding interactions of the human vitamin D receptor (hVDR)
      with the murine osteopontin vitamin D response element (mOP VDRE) was examined.
      Both recombinant hVDR and human retinoid X receptor beta (hRXRbeta) proteins were
      obtained from baculovirus-infected Sf9 insect cells. Mixing extracts of the two
      recombinant proteins resulted in the strong, specific formation of a slower
      migrating complex in the electrophoretic mobility shift assay. Crude extracts of
      the expressed hVDR alone were also capable of binding with high affinity to the
      mOP sequence, and this binding was enhanced in the presence of 1,25
      dihydroxyvitamin D3 (1,25-(OH)2D3). Competition experiments confirmed the
      specificity of this interaction and revealed that the human osteocalcin VDRE was
      a poor competitor for this binding. Ethylation interference footprint analyses of
      hVDR/hRXRbeta and hVDR complexes revealed only subtle differences in how these
      two different VDR-containing complexes interacted with the mOP VDRE. The
      footprints displayed contact points in both halves of the direct repeat format,
      confirming the dimeric and major groove interactions of both types of complexes.
      DNA affinity chromatography of labelled hVDR extracts revealed a peak eluting at
      ca. 290 mM KC1 that was capable of rebinding to the mOP sequence in gel shift
      experiments. Ultraviolet (UV) light-crosslinking experiments of hVDR extracts
      alone to radiolabelled DNA were consistent with the existence of a homodimeric
      hVDR interaction. Additionally, these experiments confirmed the direct
      interaction of a hVDR/hRXRbeta heterodimer when mixed extracts were utilized.
      From these results we infer that homodimers of the hVDR which respond with
      enhanced DNA binding to particular vitamin D response elements when exposed to
      1,25-(OH)2D3 are possible. This may be of functional significance when RXR
      proteins are limiting or RXR ligand is present within a cell.

PMID- 9010342
TI  - Changes in levels of mRNAs of transforming growth factor (TGF)-beta1, -beta2, 
      beta3, TGF-beta type II receptor and sulfated glycoprotein-2 during apoptosis of
      mouse uterine epithelium.
AB  - To examine the roles played by transforming growth factors (TGF)-beta1, -beta2, 
      beta3, and TGF-beta type II receptors in the induction of apoptosis in the mouse
      uterine epithelium after estrogen deprivation, we investigated the expression of
      their mRNAs and the mRNA of sulfated glycoprotein-2 (SGP-2). Pellets containing
      100 microg estradiol-17beta (E2) were implanted into ovariectomized mice and
      removed four days later. Apoptotic indices (percentage of apoptotic cells) of
      both luminal and glandular epithelia increased after E2 pellets were removed, but
      administration of progesterone (P), 5alpha-dihydrotestosterone (DHT), or
      continued implantation of E2 pellets suppressed this increase. Levels of mRNAs of
      TGF-beta1, -beta2, and -beta3, and SGP-2 did not increase after estrogen
      deprivation. However, estrogen deprivation caused a gradual increase in the level
      of TGF-beta type II receptor mRNA, and its level increased about six-fold six
      days later. Moreover, E2, P, and DHT markedly decreased the level of TGF-beta
      type II receptor mRNA. In situ hybridization demonstrated that mRNAs of TGF
      beta1, -beta2, -beta3 and TGF-beta type II receptor were localized to the
      epithelium. Exogenous administration of TGF-beta1 into the uterine stroma induced
      apoptosis in the epithelium, a finding that suggests that signals produced by TGF
      betas can induce apoptosis. Therefore, the present results suggest that increased
      sensitivity of uterine epithelial cells to TGF-betas, as demonstrated by an
      increase in TGF-beta type II receptor mRNA, is involved in the induction of
      apoptosis after estrogen deprivation, although signals produced by TGF-betas do
      not appear sufficient to induce apoptosis.

PMID- 9010344
TI  - Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on
      creatine kinase B activity in vitro and in vivo.
AB  - We have compared the cell and tissue selective estrogenic and antiestrogenic
      activities of tamoxifen, raloxifene, ICI 164,384 and a permanently ionized
      derivative of tamoxifen--tamoxifen methiodide (TMI). This non-steroidal
      antiestrogen has limited ability to cross the blood brain barrier and is
      therefore less likely to cause the central nervous system disturbances caused by
      tamoxifen. We have used the stimulation of the specific activity of the "estrogen
      induced protein", creatine kinase BB, as a response marker in bone, cartilage,
      uterine and adipose cells and in rat skeletal tissues, uterus and mesometrial
      adipose tissue. In vitro, TMI, tamoxifen and raloxifene mimicked the agonistic
      action of 17beta-estradiol in ROS 17/2.8 rat osteogenic osteosarcoma, female
      calvaria, and SaOS2 human osteoblast cells. In Ishikawa endometrial cancer cells,
      tamoxifen showed reduced agonistic effects and raloxifene showed no stimulation.
      However, as antagonists, tamoxifen and raloxifene were equally effective in
      Ishikawa or SaOS2 cells. In immature rats, all four of the antiestrogens
      inhibited estrogen action in diaphysis, epiphysis, uterus and mesometrial adipose
      tissue; when administered alone, tamoxifen stimulated creatine kinase (CK)
      specific activity in all these tissues. Raloxifene and TMI, however, stimulated
      only the skeletal tissues and had no stimulatory effect in the uterus or
      mesometrial fat, and the pure antiestrogen ICI 164,384 showed no stimulatory
      effect in any of the tissues. The simultaneous injection of estrogen, plus an
      antiestrogen which acted as an agonist, resulted in lower CK activity than after
      injection of either agent alone. These differential effects, in vivo and in
      vitro, may point the way to a wider therapeutic choice of an appropriate
      antiestrogen which, although antagonizing E2 action in mammary cancer, can still
      protect against osteoporosis and cardiovascular disease and not stimulate the
      uterus with its attendant undesirable changes, or interfere with the beneficial
      action of E2 in the brain.

PMID- 9010345
TI  - Characterization of 5alpha-reductase gene expression in stroma and epithelium of
      human prostate.
AB  - The expression of 5alpha-reductase type 1 and type 2 isoenzymes in hyperplastic
      human prostate tissue and several human prostate cell lines was investigated by
      Northern blot analyses, reverse transcription-polymerase chain reaction (RT-PCR),
      and enzyme activity. Separation of stroma and epithelium was confirmed
      histologically and only preparations with no apparent contamination were employed
      in the subsequent studies. Poly(A)+ RNA was isolated from stromal and epithelial
      fractions and analysed by Northern blot and RT-PCR. Inhibition of epithelial and
      stromal 5alpha-reductase activities by 17beta-N,N-diethylcarbamoyl-4-methyl-4-aza
      5alpha-androstan- 3-one (4MA) was assessed using a range of concentrations
      between 10(-13) and 10(-5) M. Results from Northern blot analyses and RT-PCR
      showed that the prostate stroma expressed 5alpha-reductase type 1 and type 2
      isoenzymes, whereas the prostate epithelium only expressed 5alpha-reductase type
      1. This was consistent with biphasic inhibition of 5alpha-reductase activity by
      4MA in stroma and monophasic inhibition in epithelium. Cultured epithelial cells
      derived from human prostate only expressed 5alpha-reductase type 1 and had Vmax
      and Km values that approximated the lower end of the range reported for
      surgically removed prostate epithelium. The foregoing data explains the disparate
      activities of 5alpha-reductase, previously reported, in stroma and epithelium.
      The differential localization of these isoenzymes in the prostate suggests that
      future therapy of androgen-sensitive disease may be more successful through the
      use of selective inhibitors of the different 5alpha-reductase isoenzymes.

PMID- 9010346
TI  - 1alpha,25-dihydroxy-24-oxo-16-ene vitamin D3, a metabolite of a synthetic vitamin
      D3 analog, 1alpha,25-dihydroxy-16-ene vitamin D3, is equipotent to its parent in
      modulating growth and differentiation of human leukemic cells.
AB  - 1alpha,25(OH)2-16-ene-D3, a synthetic analog of the steroid hormone,
      1alpha,25(OH)2D3, has great potential to become a drug in the treatment of
      leukemia and other proliferative disorders, because of its minimal in vivo
      calcemic activity associated with a potent inhibitory effect on cell growth.
      However, at present, the mechanisms through which 1alpha,25(OH)2-16-ene-D3
      expresses its biological activities are still not completely understood. Our
      previous in vitro study in a perfused rat kidney indicated for the first time
      that 1alpha,25(OH)2-16-ene-D3 and 1alpha,25(OH)2D3 are metabolized differently.
      1alpha,25(OH)2-24-oxo-16-ene-D3, an intermediary metabolite of 1alpha,25(OH)2-16
      ene-D3 formed through the C-24 oxidation pathway, accumulated significantly in
      the perfusate when compared to 1alpha,25(OH)2-24-oxo-D3, the corresponding
      intermediary metabolite of 1alpha,25(OH)2D3. In a subsequent in vivo study, we
      also reported that 1alpha,25(OH)2-24-oxo-16-ene-D3 exerted immunosuppressive
      activity equal to its parent, without causing significant hypercalcemia. In order
      to establish further the critical role of 1alpha,25(OH)2-24-oxo-16-ene-D3, in
      generating some of the key biological activities ascribed to its parent, we
      performed the present in vitro study using a human myeloid leukemic cell line
      (RWLeu-4) as a model. Comparative target tissue metabolism studies indicated that
      1alpha,25(OH)2-16-ene-D3 and 1alpha,25(OH)2D3 are metabolized differently in
      RWLeu-4 cells, and the differences were similar to the ones we previously
      observed in the rat kidney. The significant finding was the accumulation of
      1alpha,25(OH)2-24-oxo-16-ene-D3 in RWLeu-4 cells because of its resistance to
      further metabolism. Biological activity studies indicated that both
      1alpha,25(OH)2-16-ene-D3 and its 24-oxo metabolite produced growth inhibition and
      promoted differentiation of RWLeu-4 cells to the same extent, and these
      activities were several fold higher than those exerted by 1alpha,25(OH)2D3. In
      addition, the genomic action of each vitamin D compound was assessed in a rat
      osteosarcoma cell line (ROS 17/2.8) by measuring its ability to transactivate a
      gene construct containing the vitamin D response element of the osteocalcin gene
      linked to the growth hormone reporter gene. In these studies, both 1alpha,25(OH)2
      16-ene-D3 and its 24-oxo metabolite exerted similar but potent transactivation
      activity which was several fold greater than that exerted by 1alpha,25(OH)2D3
      itself. In summary, our results indicate that the production and slow clearance
      of the bioactive intermediary metabolite, 1alpha,25(OH)2-24-oxo-16-ene-D3, in
      RWLeu-4 cells contributes significantly to the final expression of the enhanced
      biological activities ascribed to its parent analog, 1alpha,25(OH)2-16-ene-D3.

PMID- 9010347
TI  - Stability of the ligand-estrogen receptor interaction depends on estrogen
      response element flanking sequences and cellular factors.
AB  - To determine whether accessory proteins mediate the ligand- and DNA sequence
      dependent specificity of estrogen receptor (ER) interaction with DNA, the binding
      of partly purified vs highly purified bovine ER to various estrogen response
      elements (EREs) was measured in the presence of different ER ligands. Partly
      purified estradiol-liganded ER (E2-ER) binds cooperatively to stereoaligned
      tandem EREs flanked by naturally occurring AT-rich sequences, with a
      stoichiometry of one E2-ER dimer per ERE. In contrast, highly purified E2-ER
      binds with a 10-fold lower affinity and non-cooperatively to EREs flanked by the
      AT-rich region. Moreover, the binding stoichiometry of highly purified E2-ER was
      0.5 E2-ER dimer, or one monomer per ERE, independent of the ERE flanking
      sequence. Interestingly, the binding of ER liganded with the antiestrogen 4
      hydroxytamoxifen (4-OHT-ER) was non-cooperative with an apparent stoichiometry of
      0.5 4-OHT-ER dimer per ERE, regardless of ER purity or ERE flanking sequence. We
      recently showed that when 4-OHT-ER binds DNA, one molecule of 4-OHT dissociates
      from the dimeric 4-OHT-ER-ERE complex, accounting for the reduced apparent
      binding stoichiometry. In contrast, ER covalently bound by tamoxifen aziridine
      (TAz) gave an ERE binding stoichiometry of one TAz-ER dimer per ERE, and TAz-ER
      binds cooperatively to multiple AT-rich EREs, regardless of the purity of the
      receptor. We have obtained evidence that purification of ER removes an accessory
      protein(s) that interacts with ER in a sequence- and/or DNA conformational
      dependent manner, resulting in stabilization of E2, but not 4-OHT, in the ligand
      binding domain when the receptor binds to DNA. We postulate that retention of
      ligand by ER maintains the receptor in a conformation necessary to achieve high
      affinity, cooperative ERE binding.

PMID- 9010349
TI  - The effects of dihydrotestosterone on the expression of p185(erbB-2) and c-erbB-2
      mRNA in the prostatic cell line LNCaP.
AB  - The c-erbB-2 proto-oncogene encodes a 185000 molecular weight protein (p185(erbB
      2)) which shares structural homology with the epidermal growth factor (EGF)
      receptor. We examined the effects of dihydrotestosterone (DHT) on the expression
      of p185(erbB2) and c-erbB-2 mRNA in the human malignant prostatic cell line
      LNCaP. LNCaP cells grown in steroid-depleted media were treated with DHT (10(-11)
      10(-6) M) for 48 h and p185(erbB-2) expression was determined by Western blotting
      and immunoprecipitation of 35S-methionine labelled p185(erbB-2). c-erbB-2 mRNA
      levels were determined using a competitive quantitative reverse transcription
      polymerase chain reaction (RT-PCR) based technique. DHT at concentrations of 10(
      9) M or greater resulted in decreased expression of p185(erbB-2). In contrast,
      DHT at these levels stimulated EGF receptor protein expression and cellular
      proliferation. c-erbB-2 mRNA levels declined to 30-50% of control levels
      following treatment with DHT of 10(-10) M or greater. Furthermore, the inhibitory
      effects on c-erbB-2 mRNA were rapid, occurring within 6-12 h of treatment. In
      summary, these results demonstrate that DHT, at concentrations that stimulate
      cell growth, inhibits the expression of p185(erbB-2) and c-erbB-2 mRNA.

PMID- 9010348
TI  - Androgen regulation of ribosomal RNA synthesis in LNCaP cells and rat prostate.
AB  - Androgen-dependent growth of prostate tissue has been well documented. An
      additional prerequisite for cellular growth is the accumulation of ribosomes. It
      is thus reasonable to hypothesize that ribosomal DNA (rDNA) transcription in
      prostate tissue must be stimulated by androgen either directly or indirectly.
      This hypothesis was tested using both LNCaP cells, an androgen-dependent tissue
      culture line and in a rat animal model. Nuclear run-on assays confirmed that the
      administration of DHT to LNCaP cells resulted in a two- to three-fold increase in
      the rate of rRNA synthesis when compared to cells maintained in the absence of
      androgen. Enzymatic analysis and Western blots were carried out to measure the
      amount (activity and mass) of RNA polymerase I in DHT treated LNCaP cells. These
      assays demonstrated that neither the catalytic activity of RNA polymerase I nor
      the amount of the enzyme varied in response to DHT. However, Western blots
      revealed that the amount of the auxiliary RNA polymerase I transcription factor
      UBF, was significantly increased (two- to three-fold) in cells grown in the
      presence of DHT. Similar experiments were carried out with prostatic tissue
      obtained from orchiectomized rats maintained on either placebo or testosterone
      pellets. In this model, both the catalytic activity as well as the amount of RNA
      polymerase I protein decreased. However, in agreement with the tissue culture
      model, UBF protein decreased in prostates from orchiectomized rats and was
      maintained in animals supplemented with testosterone. These lines of evidence are
      consistent with the hypothesis that androgens stimulate rRNA synthesis by
      increasing the quantities of the components of the rDNA transcription system.

PMID- 9010350
TI  - RU 58668: further in vitro and in vivo pharmacological data related to its
      antitumoral activity.
AB  - Previous studies with the pure antiestrogen RU 58668 showed that this compound
      proved to be highly antiproliferative in vitro, and to be the only antiestrogenic
      compound so far known to induce long-term regression of MCF-7 tumours implanted
      into nude mice. In order to obtain more insight into the therapeutic potential of
      this molecule, we performed a new set of experiments in vitro and in vivo in
      comparison with tamoxifen and/or ICI 182,780. In vitro, 1 nM RU 58668 induced an
      accumulation of MCF-7 cells in G0/G1 phases of the cell cycle within 48 h and, in
      contrast to trans-4-hydroxy-tamoxifen, blocked the invasiveness of ras
      transfected MCF-7 cells into the chick embryo heart during the three weeks of co
      culture. An in vivo dose-effect relationship study showed that RU 58668 induced a
      regression of MCF-7 tumour with as low a dose as 10 mg/kg/week, and that such an
      effect can not be obtained either with a sublethal dose of adriamycin or with ICI
      182,780, (2-250 mg/kg/week). This reduction in the tumour volumes accords with
      histological modifications of the tumours, which showed a decrease in the ratio
      of epithelial cells over the tumoral mass, and with a concomitant decrease in
      their regrowth potential when reimplanted into naive nude mice. Taken together,
      these results suggest a promising usefulness for RU 58668 in the treatment of
      metastatic breast cancer in women.

PMID- 9010352
TI  - Human dehydroepiandrosterone sulfotransferase pharmacogenetics: quantitative
      Western analysis and gene sequence polymorphisms.
AB  - Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfation of DHEA
      and other hydroxysteroids. DHEA ST enzymatic activity in individual human liver
      biopsy samples has been shown to vary over a five-fold range, and frequency
      distribution histograms are bimodal, with approximately 25% of subjects included
      in a high activity subgroup. We set out to characterize the molecular basis for
      variation in human liver DHEA ST activity. The first step involved performing
      quantitative Western analysis of cytosol preparations from 92 human liver samples
      that had been phenotyped with regard to level of DHEA ST enzymatic activity.
      There was a highly significant correlation (r(s) = 0.635, P < 0.0001) between
      levels of DHEA ST activity and immunoreactive protein. We next attempted to
      determine whether the expression of DHEA ST might be controlled, in part, by a
      genetic polymorphism. DNA was isolated from three "low" and three "high" DHEA ST
      activity liver samples. Exons and the 5'-flanking region of the DHEA ST gene
      (STD) were amplified for each of these samples with the polymerase chain reaction
      (PCR). When compared with "wild type" STD sequence, some of the samples contained
      a T --> C transition at DHEA ST cDNA nucleotide 170, located within exon 2,
      resulting in a Met 57 --> Thr change in amino acid. Other samples contained an A 
      -> T transversion at nucleotide 557 within STD exon 4 that resulted in a Glu 186 
      -> Val change. STD exons 2 and 4 were then sequenced for DNA isolated from an
      additional 87 liver samples that had been phenotyped with regard to level of DHEA
      ST enzymatic activity. The allele frequency for the exon 2 polymorphism in these
      samples was 0.027, whereas that for the exon 4 polymorphism was 0.038, but
      neither polymorphism was systematically related to the level of enzyme activity
      in these samples. Transient expression in COS-1 cells of cDNA that contained the
      nucleotide 170 and 557 polymorphisms, either separately or together, resulted in
      decreased expression of both DHEA ST enzymatic activity and level of
      immunoreactive protein, but only when the nucleotide 557 variant was present.
      Identification of common genetic polymorphisms within STD will now make it
      possible to test the hypothesis that those polymorphisms might alter in vivo
      expression and/or function of this important human steroid-metabolizing enzyme.

PMID- 9010351
TI  - Cloning and characterization of a glycogen synthase cDNA from human endometrium.
AB  - One major human uterine response to post-ovulatory progesterone is the
      accumulation of glycogen by the endometrium. A temporally related increase in
      glycogen synthase activity has been documented, but the isozyme responsible has
      not yet been identified. We have amplified a glycogen synthase (GS) complementary
      DNA (cDNA) from human endometrium by reverse transcription-polymerase chain
      reaction (RT-PCR). Overlapping clones of the PCR products provided a cDNA that is
      3534 base pairs (bp) long, including a 22-bp poly(A)+ tail, and an open reading
      frame that encodes a 737 amino acid protein with a molecular weight of 83936.
      This cDNA is almost identical to that of human striated muscle GS. Differences
      include a double nucleotide substitution at 1983-1984 and five single nucleotide
      substitutions located, respectively, at positions 379, 2457, 2470, 2477, and
      2553. These differences only alter the predicted amino acid sequence from that of
      the striated muscle protein by a single substitution at position 608. A 5'-end
      fragment plus an internal fragment of human myometrial GS cDNA were also analysed
      and were shown to have identity with the endometrial GS cDNA. Northern blot
      hybridization, using a human muscle-derived cDNA probe, detected the presence of
      a 4.0-kb GS messenger RNA (mRNA) in the endometrium and myometrium. Our results
      establish that the GS of human Mullerian tissues is, essentially, identical to
      that reported for human striated muscle.

PMID- 9010353
TI  - Sulfation by guinea pig chorion and uterus: differential action towards estrone
      and estradiol.
AB  - The activities of estrogen sulfotransferase, estrogen sulfatase and estradiol
      17beta-dehydrogenase change considerably in the guinea pig uterine compartment
      during gestation. This study was undertaken to inquire if the chorion membrane
      could influence the pattern of estrogen resulting when substrates were applied to
      the fetal surface of the chorion while it was attached, late in gestation, to the
      uterine wall. This tissue system resulted in a differential handling of estrone
      and estradiol. Estrone was largely excluded from the tissue, remaining mainly in
      free steroidal form. Estradiol was considerably converted to its 3-sulfate which
      was mainly retained by the chorion. Parallel experiments with chorion and uterus
      separately failed to discriminate between the two substrates. Hydrolysis of
      estrone sulfate and estradiol 3-sulfate was similar in all three tissue systems.
      It appears that the interaction of chorion with uterus late in gestation causes a
      difference in tissue action towards the two steroid substrates of closely related
      structure. The results suggest a limitation in tissue uptake of estrone compared
      with estradiol, or a much greater sulfotransferase activity towards estradiol.
      Whole cytosols of late gestational chorion catalyzed sulfation of estradiol at
      about double the velocity of estrone. This may only partly account for the
      difference in the intact chorion-uterine tissue system.

PMID- 9010354
TI  - Immunochemical distribution and immunohistochemical localization of 20beta
      hydroxysteroid dehydrogenase in neonatal pig tissues.
AB  - Immunochemical distribution of 20beta-hydroxysteroid dehydrogenase (HSD) in
      neonatal pig tissues was investigated by Western blot analysis of the proteins
      reacting with anti-20beta-HSD antibody. 20beta-HSD was present in all organs
      investigated: brain, lung, thymus, submandibular gland, heart, liver, kidney,
      spleen, adrenal gland, testis, epididymis, prostate, vas deferens and seminal
      vesicle. In particular, high concentrations of 20beta-HSD were detected in the
      testis, followed by the kidney and liver, by the [125I]-protein A binding method.
      Immunohistochemical localization of the enzyme was achieved in paraffin sections
      of the testis, kidney, liver, epididymis, and vas deferens by the streptoavidin
      biotin complex method. In the testis, very strong immunostaining was found only
      in interstitial Leydig cells, whereas the cells in seminiferous tubules, such as
      Sertoli cells and spermatogenic cells, were entirely negative. In the kidney,
      strong immunostaining was detected in epithelial cells of Henle's loop. The
      immunoreactive proteins were also localized in the hepatic lobules of the liver,
      tall columnar cells of the ductus epididymidis of the epididymis, and mucosal
      epithelium cells and muscularis of the vas deferens. These observations indicate
      that tissue distribution of 20beta-HSD is similar to that of carbonyl reductase
      in the human and rat. However, the specific and abundant expression of 20beta-HSD
      in testicular Leydig cells of the neonatal pig, which are concerned with the
      synthesis of androgens, suggests that 20beta-HSD has a very important
      physiological role in testicular function during the neonatal stage.

PMID- 9010355
TI  - Activity of juvenile hormone and juvenile hormone analogues on the growth of
      Trypanosoma cruzi.
AB  - The effects of juvenile hormone-III (JH-III) and the juvenile hormone analogues
      (JHA) methoprene and fenoxycarb on the growth and macromolecular biosynthesis in
      Trypanosoma cruzi were studied in vitro. It was observed that JH-III and JHA
      blocked growth and 3H-thymidine incorporation without killing the cells within
      certain concentrations (< or = 1 x 10(-4) M), but they caused cellular death at
      concentrations over 1 x 10(-3) M. The inhibitory effect on growth was partially
      reversible. On the other hand, the inhibitory action of JH-III, methoprene and
      fenoxycarb was an unspecific effect according to the results obtained with
      Leishmania mexicana mexicana (promastigotes) and human peripheral blood
      lymphocytes. The JHA have a good possibility of being used in the control of
      trypanosomiasis.

PMID- 9010356
TI  - Effects of intermittent androgen suppression on the stem cell composition and the
      expression of the TRPM-2 (clusterin) gene in the Shionogi carcinoma.
AB  - The proportion of tumorigenic stem cells and the expression of the apoptosis
      related gene, TRPM-2 (clusterin), were studied in populations of Shionogi
      carcinoma cells subjected to multiple cycles of androgen withdrawal and
      replacement (intermittent androgen suppression). The parent androgen-dependent
      cell line was initially transplanted into a male mouse which was castrated when
      the estimated weight of the resultant tumour became approximately 3 g. After the
      tumour had regressed to 40% or less of the original weight, it was transplanted
      into the next non-castrated male. This was repeated for four cycles of
      transplantation and castration-induced apoptosis before the tumour progressed to
      an androgen-independent state. The proportion of total stem cells in the tumour,
      as determined by in vivo limiting dilution assays in male mice, was constant
      during the first three cycles but increased 15-fold between the third and fourth
      cycles. In the parent androgen-dependent tumour before androgen ablation, the
      androgen-independent stem cell population formed 0.8% of the total stem cell
      compartment. After the fourth cycle this population increased to 47%; a
      population of similar size (33%, P = 0.8) was found in the androgen-independent
      recurrent form of the tumour induced by one-time castration. Whether androgen
      withdrawal therapy was intermittent or continuous, conversion to androgen
      independence thus occurred when one-third to one-half of the total stem cell
      compartment was populated by androgen-independent stem cells. The androgen
      repressed TRPM-2 (clusterin) gene was actively expressed in regressing tumours
      after androgen ablation, and also became constitutively expressed in non
      regressing tumours after the first and subsequent cycles of androgen withdrawal.
      Staining of cytoplasm and nuclei with anti-clusterin antibody was observed in
      androgen-dependent tumour cells after each cycle of intermittent androgen
      suppression; the nuclear staining was more intense in recurrent androgen
      independent cells. The anomalous nuclear localization of clusterin, an anti
      cytolytic TRPM-2 encoded protein, may serve to inhibit early events in the
      apoptotic process and thereby foster the generation and outgrowth of androgen
      independent stem cells in an androgen-depleted environment.

PMID- 9010357
TI  - Chronic back pain and substance abuse.

PMID- 9010359
TI  - Appetite suppressants for obesity.

PMID- 9010360
TI  - Hair loss associated with nefazodone.

PMID- 9010361
TI  - Newborn length of stay.

PMID- 9010362
TI  - Topical ointments and wound healing.

PMID- 9010363
TI  - Treatment of hyperlipidemia in women.

PMID- 9010364
TI  - Anticoagulants in acute MI.

PMID- 9010365
TI  - Acyclovir in pregnancy for primary prevention of neonatal herpes.

PMID- 9010366
TI  - Lipid lowering in post-MI patients with normal cholesterol.

PMID- 9010367
TI  - Intravaginal misoprostol: a new option for labor induction?

PMID- 9010368
TI  - Birth outcomes in pregnant women taking fluoxetine.

PMID- 9010369
TI  - Medications that may contribute to sexual disorders. A guide to assessment and
      treatment in family practice.
AB  - Approximately 15% to 25% of family practice patients have concerns about sexual
      function and are most comfortable discussing these issues with their family
      physician. While many physicians have avoided this topic in the past, citing lack
      of knowledge and skill, the family practice setting is ideal for a preliminary
      evaluation of sexual dysfunction and treatment for certain etiologies. This
      especially is true for changes in sexual function secondary to medication
      effects. This article provides basic guidelines designed to assist physicians in
      evaluating the effects of medications and other substances on sexual function.
      Also included are lists of medications known or suspected to have adverse effects
      on sexual function. Physicians are encouraged to address the sexual concerns of
      their patients and to incorporate these guidelines and the medication lists into
      their evaluation.

PMID- 9010370
TI  - Electronic medical records in family practice: the time is now.

PMID- 9010371
TI  - Evaluation of suspected urinary tract infection in ambulatory women: a cost
      utility analysis of office-based strategies.
AB  - BACKGROUND: The purpose of this study was to determine the most cost-effective
      strategy for managing suspected urinary tract infections in otherwise healthy
      adult women presenting to their primary care physician with dysuria and no
      symptoms or signs of pyelonephritis. Several office-based management strategies
      are considered: empiric therapy, use of dipstick analysis, use of complete
      urinalysis, and several strategies using office or laboratory cultures. METHODS:
      We constructed a decision tree using model probabilities obtained from the
      literature. Where published probabilities were unavailable, we used extensive
      sensitivity analyses. Utilities were obtained from the Index of Well-Being. We
      obtained costs by surveying hospitals, physicians, and pharmacies. RESULTS: The
      most cost-effective strategy is to treat empirically ($71.52 per quality-adjusted
      life month, QALM). When the cost of antibiotics exceeds $74.50 or if the prior
      probability of having a UTI is under 0.30, then treatment guided by the results
      of a complete urinalysis is preferred. While it was the preferred strategy, other
      strategies (complete urinalysis, culture and treat, and dipstick testing only)
      were associated with greater utility. The marginal cost-effectiveness of these
      strategies compared with empiric therapy ranged from $2964 to $48,460 per
      additional QALM. CONCLUSIONS: The preferred strategy of empiric therapy is robust
      over a wide range of sensitivity analyses. While empiric therapy is associated
      with the best cost-utility ratio, doing a culture yields the greatest utility at
      greater incremental cost per QALM. Many primary care physicians already treat
      UTIs empirically with antibiotics. This study confirms that empiric therapy,
      while frowned upon by some, is a cost-effective strategy. Other strategies may be
      considered, but at greater marginal cost. Ultimately these findings need to be
      confirmed in clinical trials.

PMID- 9010372
TI  - Charges for obstetric liability insurance and discontinuation of obstetric
      practice in New York.
AB  - BACKGROUND: The study objective was to determine whether New York physicians
      facing higher charges for obstetric liability insurance coverage are more likely
      to discontinue obstetric practice than physicians experiencing lower levels of
      increases in liability insurance charges. METHODS: We performed a physician-level
      analysis of factors predicting discontinuation of hospital-based obstetric
      practice by 1989 for physicians active in obstetrics in 1980. We examined both
      physicians who became completely clinically inactive in New York between 1980 and
      1989, and physicians who remained clinically active but restricted their hospital
      practice to areas other than obstetrics. Multiple logistic regression models were
      used to analyze predictors of discontinuation of obstetrics, including regional
      malpractice insurance charges, physician characteristics, and practice
      characteristics. RESULTS: Although increases in malpractice insurance charges
      differed considerably among regions within New York State, there was no
      association between level of increase of charges for liability insurance and
      discontinuation of obstetric practice. A greater number of years since medical
      licensure was associated both with complete discontinuation of hospital practice
      in New York and selective discontinuation of obstetrical practice. Compared with
      obstetrician-gynecologists, family physicians were less likely to become
      completely clinically inactive. Among physicians who remained clinically active
      in hospital care, however, family physicians were less likely than obstetrician
      gynecologists to continue to include obstetrics in their practice. CONCLUSIONS:
      There is no relationship between the level of increase in liability insurance
      premiums and the likelihood of discontinuing obstetric practice in New York.
      Discontinuation of obstetric practice appears to mainly reflect trends in the
      physician's life cycle of practice activity and in the scope of family and
      general practice.

PMID- 9010373
TI  - Paracervical block diminishes cramping associated with cryosurgery.
AB  - BACKGROUND: The choice of treatment method for cervical intraepithelial neoplasia
      can be dictated by the lesion size, by comfort of the operator with the
      technique, by the cost of the procedure, and by patient comfort with the
      procedure. The purpose of this research was to compare the usual method of
      cryosurgery (no anesthetic block) with a method using a paracervical block to
      reduce the pain and cramping associated with cryosurgery. METHODS: A prospective
      trial was designed and conducted in a colposcopy clinic. Of the 85 women enrolled
      in the study, all were immediately given 550 mg of naproxen sodium orally; 40
      received no block and 45 received a paracervical block before the cryosurgery
      procedure. After the procedure, a trained interviewer elicited pain and cramping
      scores using a visual analog scale. Chi-square, Fisher's exact test, Mann-Whitney
      U, Wilcoxon signed-ranks test, Friedman's two-way analysis of variance, and
      multivariate analysis of variance with covariates were used to analyze the data.
      RESULTS: Each part of the double-freeze cryosurgical procedure was ranked
      according to the participants' perceptions of pain and cramping. The cramping
      after the first freeze was significantly less for women receiving the
      paracervical block than for the women undergoing the usual procedure (z = -2.44,
      P = .014). Including the discomfort from the injection itself, the women who
      received a paracervical block perceived less cramping overall during cryosurgery
      than the women with no block (z = -2.35, P = .019). The paracervical block did
      not decrease the pain from cryosurgery according to the participants' rankings of
      perceived pain. CONCLUSIONS: A paracervical block is effective in reducing the
      cramping from cryosurgery.

PMID- 9010374
TI  - Presentation and management of childhood psychosocial problems.
AB  - BACKGROUND: Between 15% and 25% of children who visit primary care physicians
      have emotional, behavioral, or psychiatric problems that affect their
      functioning. The majority of these children are treated by primary care
      physicians. The purpose of this study was to examine the presentation and
      treatment of children's psychosocial problems in primary care and to investigate
      ways in which physician management of a problem is related to parent-physician
      agreement that the problem exists. METHODS: Twenty-six physicians at an
      ambulatory care center of a community-based, university-affiliated family
      medicine training program collected data during outpatient visits of 898 children
      aged 2 to 16 years. The physicians used a checklist to collect data on children's
      developmental problems, parents' concerns about the psychosocial functioning of
      their children, whether physicians and parents were in agreement about these
      concerns, and the parents' influence on physicians' management of the problems.
      RESULTS: Family physicians and parents agreed that 10% of the children were
      experiencing psychosocial problems. For 5% of children, physicians recorded
      emotional or behavioral concerns when parents did not disclose any such concerns.
      For only 1.8% of children, parents raised psychosocial concerns while physicians
      did not. Physicians diagnosed and managed psychosocial concerns during both acute
      care and well-child visits. When parents and physicians agreed on the presence of
      pediatric psychosocial problems, referral to a mental health professional was
      more likely than when they disagreed (60% vs 16%). CONCLUSIONS: Pediatric
      psychosocial concerns are raised by parents during acute-care and well-child
      visits. Family physicians identified and managed these problems at rates
      consistent with past research. Management strategies appeared to differ as a
      function of agreement between physicians and parents on whether a problem
      existed.

PMID- 9010376
TI  - The appropriateness of early discharge of hospitalized children with suspected
      sepsis.
AB  - BACKGROUND: Febrile children with suspected sepsis are often hospitalized and
      empirically treated with parenteral antibiotics pending results of bacterial
      cultures. The question of just how long such children should be observed and
      treated following initial negative culture reports has not been adequately
      addressed. This study was designed to determine the appropriateness of
      discharging hospitalized culture-negative children with suspected sepsis at the
      end of 48 hours. METHODS: All children admitted with a diagnosis of "suspected
      sepsis" over an 8-month period were prospectively evaluated. Based on initial
      culture data, children were divided into two groups: group A with positive
      bacterial cultures and group B with negative bacterial cultures. Clinical
      assessment and review of cerebrospinal fluid, blood, and urine culture data were
      made at 24 hours, 48 hours, and until discharge, and at 2 weeks following
      discharge of all group B patients. RESULTS: Of the 83 children enrolled in the
      study, 8 (9.5%) patients had a culture positive for bacterial infection (group
      A): meningitis in two, bacteremia in six, and urinary tract infection in two. All
      cultures were positive within 48 hours. Cultures were negative at 48 hours in the
      remaining 75 (90.4%) children (group B), and remained negative until discharge
      and at 2-week follow-up. Eight (10.6%) patients had received antibiotics prior to
      admission. After the workup, 37 of 73 (50.6%) children received antibiotics for
      less than 48 hours, while 36 (49.4%) children did so for more than 48 hours.
      Clinical assessment was normal at 48 hours in 71 of the 75 children. Sixty-three
      (84%) children available for follow-up continued to do well after discharge. No
      statistical distinction could be made between those children who remained
      hospitalized after 48 hours and those children who were dismissed at 48 hours.
      CONCLUSIONS: Although our study data suggest that culture-negative children
      hospitalized for suspected sepsis who meet the criteria for normal clinical
      assessment can be safely discharged at 48 hours, a stronger statistical
      validation of this approach can be made if a larger sample size is studied.

PMID- 9010375
TI  - Patients with HIV/AIDS: physicians' knowledge, attitudes, and referral practices.
AB  - BACKGROUND: This study investigated Massachusetts family physicians' current care
      and referral practices with respect to HIV/AIDS patients and examined actors that
      might influence family physicians in referring these patients to specialists.
      Educational opportunities for physicians with regard to HIV were also examined.
      METHODS: In 1994, a 2-page survey was mailed to the 468 members of the
      Massachusetts Academy of Family Physicians. The survey questionnaire examined
      such factors as whether the respondents were teaching or nonteaching, rural or
      urban; number of years since medical school or residency training; and knowledge
      and attitudes with regard to HIV/AIDS patients. The data were analyzed using
      Student's t test, chi-square, and correlation analysis. RESULTS: Usable responses
      were returned by 281 (60%) of the physicians surveyed. Of these, 65% reported
      having HIV patients in their practice, and 46% reported having AIDS patients was
      being managed alone by 53% of these physicians, and 11% managed their patients
      with AIDS. Physicians providing care for HIV/AIDS patients were more likely to be
      practicing in urban locations, have three or more HIV/AIDS patients in their
      practice, or recently graduated from residency. Additionally, they were more
      likely to be involved in residency teaching programs. Those who did not care for
      HIV/AIDS patients felt less knowledgeable about HIV/AIDS care, and felt that they
      had no time in their practice to care for this population of patients. Physicians
      with HIV patients learn more about HIV care from their colleagues than those
      without HIV patients. CONCLUSIONS: Family physicians are increasingly seeing
      HIV/AIDS patients in their offices. The majority are continually caring for these
      patients, either by themselves or co-managing their care with a specialist. Local
      CME programs relying on colleagues and community resources to discuss management
      of these patients may be one of the best ways of ensuring that increasing numbers
      of family physicians obtain the appropriate knowledge to care for these patients
      within their own communities.

PMID- 9010378
TI  - New perspectives of the pathogenesis of coeliac disease: evolution of a working
      clinical definition.

PMID- 9010377
TI  - Clostridium difficile colitis presenting as an acute abdomen: case report and
      review of the literature.
AB  - Pseudomembranous colitis associated with Clostridium difficile rarely manifests
      as an acute abdomen and even more rarely as an acute abdomen without abnormal
      radiologic studies. The following is a case report of a 52-year-old white man who
      had an acute abdomen without abnormal radiologic studies, and was given a final
      diagnosis of C difficile colitis. Surgery was averted only by the ability to do
      an expeditious flexible sigmoidoscopy with the visualization of pseudomembranes.
      Diagnosis was later confirmed by a positive toxin assay and culture of C
      difficile. Treatment for C difficile colitis is usually medical, with oral
      vancomycin the preferred agent. Surgery may be needed when there is an acute
      abdomen with other systemic signs (fever or leukocytosis) or abnormal radiologic
      studies.

PMID- 9010379
TI  - Helicobacter pylori--can the mechanisms of pathogenesis guide us towards novel
      strategies for treatment and prevention?
AB  - Helicobacter pylori establishes a chronic infection in the stomach of humans. The
      infection is associated with a low grade inflammatory response in the epithelium
      that can develop into chronic active gastritis, peptic ulcer disease or
      neoplasia. Antibiotics have dramatically decreased the rate of recurrence of
      peptic ulcers. However, antibiotic resistance is already evident, casting doubts
      on the future efficacy of these strategies. The link between childhood infection
      and severe health problems, including increased risk for gastric tumours motivate
      efforts to develop vaccines. Characterization of the molecular mechanisms of
      pathogenesis will pave the way for novel strategies for treatment and prevention
      of H. pylori infection.

PMID- 9010380
TI  - Determinants of longevity: genetic, environmental and medical factors.
AB  - This review focuses on the determinants of longevity in the industrialized world,
      with emphasis on results from recently established data bases. Strong evidence is
      now available that demonstrates that in developed countries the maximum lifespan
      as well as the mean lifespan have increased substantially over the past century.
      There is no evidence of a genetically determined lifespan of around 85 years. On
      the contrary, the biggest absolute improvement in survival in recent decades has
      occurred amongst 80+ year-olds. Approximately one-quarter of the variation in
      lifespan in developed countries can be attributed to genetic factors. The
      influence of both genetic and environmental factors on longevity can potentially
      be modified by medical treatment, behavioural changes and environmental
      improvements.

PMID- 9010381
TI  - Thrombolysis in the management of limb arterial occlusion. Towards a consensus
      interim report. Working Party on Thrombolysis in the Management of Limb
      Ischaemia.

PMID- 9010383
TI  - Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a).
AB  - OBJECTIVES: Lipoprotein(a) consists of an LDL-particle attached to
      apolipoprotein(a), which is made by the liver. Diterpenes present in boiled
      coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine
      aminotransferase in man. We investigated the association between intake of boiled
      coffee and serum levels of lipoprotein(a). DESIGN, SETTING AND SUBJECTS: Healthy
      Norwegians 40-42 years of age, who habitually consumed five or more cups of
      boiled coffee per day (n = 150) were compared with matched filter coffee
      consumers (n = 159) in a cross-sectional study, as part of the Norwegian National
      Health Screening in 1992. RESULTS: The median lipoprotein(a) level was 13.0 mg dL
      1 (10th and 90th percentile: 2.5 and 75.0 mg dL-1, respectively) on boiled and
      7.9 mg dL-1 (10th and 90th percentile: 1.9 and 62.5 mg dL-1, respectively) on
      filter coffee (P = 0.048). Means +/- SE were 25.8 +/- 2.4 mg dL-1 and 19.6 +/-
      2.0 mg dL-1, respectively (P = 0.04). Although not statistically significant,
      subjects consuming nine or more cups of coffee per day had higher lipoprotein(a)
      levels than those drinking five to eight cups per day in both coffee groups.
      CONCLUSION: Chronic consumers of unfiltered, boiled coffee have higher serum
      levels of lipoprotein(a) than filter coffee drinkers.

PMID- 9010382
TI  - Hyperparathyroidism and long-term lithium therapy--a cross-sectional study and
      the effect of lithium withdrawal.
AB  - OBJECTIVES: To assess in patients with long-term lithium treatment the incidence
      and prevalence of hypercalcaemia and hyperparathyroidism, and to evaluate the
      relationship between parathyroid function and renal function: also, to examine
      the effect of treatment discontinuation. DESIGN: Part 1. An epidemiological cross
      sectional study covering defined catchment areas. Part 2. A lithium withdrawal
      study in a subgroup of the patients who were examined after a mean of 8.5 (4-16)
      weeks off lithium. Comparisons were made with a group of psychiatric non-lithium
      patients matched for sex and age. SETTING: Outpatient treatment at nine
      psychiatric departments in southern Sweden. SUBJECTS: Inclusion criterion was 15
      years or more on lithium. Excluded from Part 2 were patients with a high risk of
      relapse. Out of 215 identified patients. 142 (66%) entered and completed Part 1,
      while 13 of the latter entered and completed Part 2. RESULTS: The point
      prevalence of persistent hypercalcaemia was 3.6% and of surgically verified
      hyperparathyroidism 2.7%. The observed incidence of hyperparathyroidism over 19
      years was 6.3%. It was significantly higher than expected in females. In the
      withdrawal group serum calcium was significantly increased compared to controls,
      and did not change during 8.5 weeks without lithium. Isostenuria was
      significantly more common among patients with than without hyperparathyroidism.
      CONCLUSIONS: The point prevalence, and the 19-year incidence of
      hyperparathyroidism, were increased. The point prevalence of hypercalcaemia was
      also increased, and not reversible during 8.5 weeks off lithium. The findings
      support the hypothesis of a causal relationship between lithium treatment and
      hyperparathyroidism. Hypercalcaemia and hyperparathyroidism are sometimes
      aetiologically related to reduced renal function in long-term lithium patients.

PMID- 9010384
TI  - Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the impact of chronic inflammation on lipoprotein lipase
      (LPL) levels and tri-glyceride metabolism in patients wit rheumatoid arthritis
      (RA). DESIGN: Plasma levels of LPL activity and mass before and after heparin
      were determined in post-menopausal women with active RA and in controls. The
      results were related to lipid levels and inflammatory variables. The LPL activity
      and mass together with triglyceride levels were also measured before and 6 h
      after an oral fat load. SETTING: The study was performed on in- and outpatients
      at a University Rheumatology clinic. The controls came from the same reference
      area. SUBJECTS: Altogether 17 consecutive postmenopausal female patients with RA
      and 16 age and sex matched controls were enrolled for the initial determination
      of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the
      fat load. Of these, one patient and one control were excluded. MAIN OUTCOME
      MEASURES: LPL determination: basal levels and post-heparin levels of LPL activity
      and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides),
      lipoprotein levels (high density lipoprotein, HDL: low density lipoprotein, LDL),
      erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid,
      haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor alpha. TNF
      alpha: interleukin 1 beta, IL-1 beta: and interleukin-6. IL-6). Fat tolerance
      test: LPL activity. mass and triglyceride levels before and 6 h after a per oral
      fat load. RESULTS: Pre-heparin LPL mass (P < 0.01) and activity (P < 0.01) were
      significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no
      correlation to the lipid levels, but an inverse correlation to several
      inflammatory parameters: it was significant for orosomucoid (rs = -0.63, P <
      0.05) and C-reactive protein (CRP) (rs = -0.54, P < 0.05) and close to
      significant for haptoglobin (rs = -0.48, P = 0.087) and IL-6 (rs = -0.52, P =
      0.061). Six hours after.a lipid load the LPL activity and mass were significantly
      lower in RA (P < 0.05 and P < 0.01, respectively) but the triglyceride level was
      not significantly different compared to controls. CONCLUSION: An inverse
      relationship exists between inflammatory status and pre-heparin LPL mass.
      Preheparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This
      has been shown to hinder the uptake of remnant lipoprotein particles through
      competition with lipoprotein bound dimeric LPL for the LDL receptor-related
      protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of
      the level of monomeric LPL in plasma may thus be beneficial for remnant
      catabolism. The same mechanism may on the other hand increase macrophage uptake
      of lipids. This may not affect global lipid metabolism but may be important in
      driving the atherosclerotic process in the vessel wall.

PMID- 9010385
TI  - Clinical features in persons with a family history of diabetes compared to
      controls (The Second Generation Fredericia Study).
AB  - OBJECTIVE: To compare clinical and biochemical features in non-diabetic persons
      with a family history of non-insulin dependent diabetes mellitus (NIDDM) to non
      diabetic persons without a family history of diabetes. DESIGN: Cross-sectional
      study. SETTING: Population-based survey in Fredericia, Denmark. SUBJECTS: Seven
      hundred and forty subjects, the second generation of an earlier defined cohort
      was examined. The median age was 48 (range 26-65) years. Of the 740 subjects 696
      were non-diabetic. INTERVENTIONS: The subjects had a clinical examination. MAIN
      OUTCOME MEASURES: Known risk factors for development of diabetes and
      cardiovascular disease. RESULTS: More offspring of diabetic persons had NIDDM
      (chi 2 = 6.36, P < 0.05). Non-diabetic males with a family history of diabetes
      had a higher BMI fasting blood glucose, and triglycerides compared to males
      without a family history of diabetes. Non-diabetic females with a family history
      of diabetes had a higher BMI, fasting blood glucose. HbA1C, diastolic blood
      pressure, and lower HDL-cholesterol than female offspring of non-diabetics. In a
      multiple regression model we found that non-diabetic off-spring of diabetic
      persons had higher fasting blood glucose and HbA1C compared to offspring of non
      diabetic persons when adjusted for the independent variables age, BMI, WHR, and
      sex. CONCLUSION: Our results may indicate that the only inherited factors from
      NIDDM patients are plasma blood glucose. HbA1C and increased BMI which may be an
      indication for later diabetes, whereas other cardiovascular risk factors may be
      inherited independently of diabetes but associated with BMI.

PMID- 9010386
TI  - Relations between vasoactive hormones and diastolic function in hypertensive
      uraemic patients.
AB  - BACKGROUND: Arterial hypertension is a significant risk factor for the high rate
      of cardiovascular disease in chronic uraemic (CU) patients. Any role that
      hypertension may play in CU patient outcomes assumes added significance. The
      elevation of some hormonal factors in early clinical stage could represent a
      valuable marker of cardiac disease in CU. AIM: This study first investigated the
      role of several hormones on cardiac diastolic properties in CU patients.
      Moreover, the study investigated the association of hypertension with both
      diastolic function and release of vasoactive hormones in CU patients. RESULTS: We
      have reported that the early impairment of diastolic function is correlated with
      the elevation of both circulating plasma atrial natriuretic factor and endothelin
      1 (ET-1) in hypertensive CU patients. Since the effect of ET-1 on diastolic
      function is still poorly understood, we have investigated also this issue. In
      eight additional patients with reduced E/A ratio, but without uraemia,
      hypertension or chronic heart failure, we have showed a high inverse correlation
      between the values of E/A ratio and ET-1 plasma concentrations. CONCLUSIONS:
      These results strongly suggest that the elevation in ET-1 levels was correlated
      with diastolic dysfunction in man. This phenomenon may have important
      pathophysiological implications suggesting the possibility of an early
      therapeutic approach in these patients.

PMID- 9010387
TI  - Use of low molecular weight heparin (dalteparin), once daily, for the treatment
      of deep vein thrombosis. A feasibility and health economic study in an outpatient
      setting. Swedish Venous Thrombosis Dalteparin Trial Group.
AB  - OBJECTIVES: To test the safety and feasibility of treating deep vein thrombosis
      (DVT) in an outpatient setting, using the low molecular weight heparin
      dalteparin, to calculate the potential and actual cost reductions achievable as a
      result of such a treatment regimen. DESIGN: An open, nonrandomized, multicentre
      trial. SETTING: Fourteen hospitals in central Sweden. SUBJECTS: Ambulant
      patients, aged 18 years or older. with symptomatic DVT in the leg, diagnosed
      using phlebography or ultrasound (Duplex-Doppler). INTERVENTIONS: Dalteparin
      (Fragmin) at a fixed dose of 200 i.u. kg-1 body weight, was administered once
      daily subcutaneously for at least 4 consecutive days. Treatment with warfarin was
      initiated from the first day of dalteparin administration. Outpatient treatment
      was encouraged whenever possible Financial calculations were performed
      independently at two hospitals, giving an average cost for all actions. OUTCOME
      MEASURES: Increasing severity of symptoms (or thromboembolic recurrences during
      the 3-months follow-up period), pulmonary embolism (PE), bleeding events, and
      death during the initial phase and follow-up period. RESULTS: Of 434 patients,
      35% and 64% were treated in hospital within 24 and 72 h, respectively, and
      thereafter as outpatients. The overall frequency of serious complications was
      0.92% (exact 95% confidence interval, 0.25-2.35%) during the initial phase and
      one patient suffered a PE and three patients had a recurrent DVT during the
      follow-up period. A cost reduction of 2705529 Swedish crowns (34.5%) was achieved
      in this study compared with traditional in-patient treatment. CONCLUSIONS:
      Dalteparin, administered subcutaneously, once daily, for the initial treatment of
      DVT yields large cost reductions and is well tolerated and effective in an
      outpatient setting.

PMID- 9010388
TI  - Possible increased risk of rhabdomyolysis during concomitant use of simvastatin
      and gemfibrozil.
AB  - The occurrence of rhabdomyolysis is one of the rare side-effects of the
      cholesterol-lowering agent simvastatin. During the use of lovastatin, an agent
      related to simvastatin, the risk of this side-effect might be increased when
      cyclosporin or gemfibrozil are used concomitantly. It is possible that this also
      applies for simvastatin. We present two patients who developed rhabdomyolysis
      during the concomitant use of simvastatin and gemfibrozil.

PMID- 9010389
TI  - The influence of female sex steroids on glucose metabolism and insulin action.

PMID- 9010391
TI  - Crawford Williamson Long (1815-78).

PMID- 9010390
TI  - Surgery for Parkinson's disease.

PMID- 9010392
TI  - Neurological picture. Reversibility of brain lesions in eclampsia.

PMID- 9010393
TI  - Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON
      Collaborative Study. European Community Concerted Action on the Epidemiology of
      Parkinson's disease.
AB  - OBJECTIVES: To assess and compare the prevalence of parkinsonism and Parkinson's
      disease in five European populations that were surveyed with similar methodology
      and diagnostic criteria. METHODS: Joint analysis of five community surveys-
      Gironde (France), eight centres in Italy, Rotterdam (The Netherlands), Girona
      (Spain), and Pamplona (Spain)--in which subjects were screened in person for
      parkinsonism. Overall, these surveys comprised 14,636 participants aged 65 years
      or older. RESULTS: The overall prevalence (per 100 population), age adjusted to
      the 1991 European standard population, was 2.3 for parkinsonism and 1.6 for
      Parkinson's disease. The overall prevalence of parkinsonism for the age groups 65
      to 69, 70 to 74, 75 to 79, 80 to 84, and 85 to 89 years was respectively, 0.9,
      1.5, 3.7, 5.0, and 5.1. The corresponding age specific figures for Parkinson's
      disease were 0.6, 1.0, 2.7, 3.6, and 3.5. After adjusting for age and sex, the
      prevalence figures did not differ significantly across studies, except for the
      French study in which prevalence was lower. Prevalence was similar in men and
      women. Overall, 24% of the subjects with Parkinson's disease were newly detected
      through the surveys. CONCLUSIONS: Prevalence of both parkinsonism and Parkinson's
      disease increased with age, without significant differences between men and
      women. There was no convincing evidence for differences in prevalence across
      European countries. A substantial proportion of patients with Parkinson's disease
      went undetected in the general population.

PMID- 9010394
TI  - Hallucinations and signs of parkinsonism help distinguish patients with dementia
      and cortical Lewy bodies from patients with Alzheimer's disease at presentation:
      a clinicopathological study.
AB  - OBJECTIVES: To compare, in a retrospective clinicopathological study, the
      presentation features of patients with dementia and cortical Lewy bodies (Lewy
      body dementia) with those of patients with Alzheimer's disease. METHODS: From a
      population of 426 cases from the dementia brain bank, 39 cases of Lewy body
      dementia and 61 cases of Alzheimer's disease with presentation details were
      identified. RESULTS: The Lewy body dementia group had significantly more frequent
      hallucinations (23% v 3%, P = 0.006) and signs of parkinsonism (41% v 5%, P <
      0.0001) than the Alzheimer's disease group. The Lewy body dementia group also had
      a greater proportion of men (62% v 34%, P = 0.013). CONCLUSION: Hallucinations
      and signs of parkinsonism help distinguish Lewy body dementia from Alzheimer's
      disease at presentation. These indicators may not be very sensitive, because they
      were reported for less than half of the patients with Lewy body dementia.

PMID- 9010395
TI  - Rhythmic auditory-motor facilitation of gait patterns in patients with
      Parkinson's disease.
AB  - OBJECTIVES: The effect of rhythmic auditory stimulation (RAS) on gait velocity,
      cadence, stride length, and symmetry was studied in 31 patients with idiopathic
      Parkinson's disease, 21 of them on (ON) and 10 off medication (OFF), and 10
      healthy elderly subjects. METHOD: Patients walked under four conditions: (1)
      their own maximal speed without external rhythm; (2) with the RAS beat frequency
      matching the baseline cadence; (3) with RAS 10% faster than the baseline cadence;
      (4) without rhythm to check for carry over from RAS. Gait data were recorded via
      a computerised foot switch system. The RAS was delivered via a 50 ms square wave
      tone embedded in instrumental music (Renaissance style) in 2/4 metre prerecorded
      digitally on a sequencer for variable tempo reproduction. Patients on medication
      were tested in the morning 60-90 minutes after medication. Patients off
      medication were tested at the same time of day 24 hours after the last dose.
      Healthy elderly subjects were tested during the same time of day. RESULTS: Faster
      RAS produced significant improvement (P < 0.05) in mean gait velocity, cadence,
      and stride length in all groups. Close synchronisation between rhythm and step
      frequency in the controls and both Parkinson's disease groups suggest evidence
      for rhythmic entrainment mechanisms even in the presence of basal ganglia
      dysfunction. CONCLUSIONS: The results are consistent with and extend prior
      reports of rhythmic auditory facilitation in Parkinson's disease gait when there
      is mild to moderate impairment, and suggest a technique for gait rehabilitation
      in Parkinson's disease.

PMID- 9010396
TI  - Decreased N-acetyl-aspartate/choline ratio and increased lactate in the frontal
      lobe of patients with Huntington's disease: a proton magnetic resonance
      spectroscopy study.
AB  - BACKGROUND: Both the effect of the mutation and the pathogenesis of Huntington's
      disease are unknown and a lack of biological markers for the natural history of
      the disease impedes the evaluation of novel therapeutic approaches. METHODS:
      Proton magnetic resonance spectroscopy was carried out on a frontal region of the
      cortex in 17 patients with clinically overt Huntington's disease and four
      asymptomatic gene carriers. RESULTS: Eight of 17 (47%) clinically affected
      patients with Huntington's disease and each of the asymptomatic carriers had
      lactate peaks in the frontal cortex which were not present in controls. The N
      acetyl-aspartate/choline (NAA/Ch) ratio was significantly reduced in the
      symptomatic patients indicating the presence of neuronal loss. The reduction was
      related to the clinical severity of the disease and was absent in the
      asymptomatic carriers. CONCLUSION: The finding of lactate peaks supports the
      hypothesis that disturbed cerebral energy metabolism contributes to the
      pathogenesis of Huntington's disease.

PMID- 9010397
TI  - The stiff leg syndrome.
AB  - Four patients had a chronic progressive disorder beginning in middle age and
      involving stiffness and painful spasms of the lower limbs. Spasms were
      spontaneous, reflex, and induced by voluntary movement. Patients had rigidity and
      abnormal postures of one or both legs. There was no truncal rigidity or
      exaggerated lumbar lordosis. Despite the presence of symptoms for up to 16 years,
      symptoms and signs of brainstem, pyramidal, and sensory dysfunction were absent.
      Sphincter disturbance developed after many years in one patient. Extensive
      investigation, including imaging of the whole neuroaxis, failed to disclose a
      cause. Anti-GAD antibodies were absent. Baclofen and diazepam led to some
      reduction in the painful spasms, but patients remained disabled by the condition.
      There were four core electrophysiological features. (1) Continuous motor unit
      activity was present at rest in at least one limb muscle. (2) Spasms tended to
      involve the repetitive grouped discharge of motor units. (3) Cutaneomuscular
      reflexes were abnormal. (4) There was little or no electrophysiological evidence
      of long tract disturbance. The patients form a characteristic syndrome, separate
      from the stiff man syndrome, and distinguishable from encephalomyelitis with
      rigidity. It is suggested that the condition is due to a chronic spinal
      interneuronitis.

PMID- 9010398
TI  - Measurement of post-traumatic amnesia: how reliable is it?
AB  - OBJECTIVE: To develop and test a clinical protocol for determining post-traumatic
      amnesia by retrospective questioning. To establish its limits and factors which
      influence reliability. DESIGN: Two independent assessments using the Rivermead
      post-traumatic amnesia protocol were undertaken by separate observers on various
      groups of patients at various time intervals. Analysis investigated the
      correlations between assessments, the percentage difference between assessments,
      the number of patients changing category, and the differences between these
      analyses in the different patient subgroups. Assessments were undertaken both in
      hospital and in the patients' homes. Four different patient groups were studied.
      These were group A: 12 inpatients with very severe head injury late after injury;
      Group B: 40 patients interviewed at home six months after injury; group C: 22
      patients interviewed within a few weeks of injury at home; group D: 116 patients
      interviewed initially within a few weeks and then at six months, on both
      occasions at home. The Rivermead post-traumatic amnesia protocol involved
      clinical questioning of the patient to establish how long after injury (in
      hours/days/weeks) the patient regained continuous day to day memory. All periods
      of coma were included. Severity was categorised with standard criteria. RESULTS:
      Overall correlation was good (Spearman's r 0.79), but the correlation was lower
      for patients with post-traumatic amnesia < 24 hours and when there was a long
      delay between assessments. In all groups 19%-25% of patients changed categories
      between assessments, but only 2% changed by two categories. CONCLUSIONS: The
      assessment of post-traumatic amnesia with the Rivermead post-traumatic amnesia
      protocol is reasonably reliable. The misclassification rate however, is
      significant enough that some caution should be taken in individual cases. Other
      evidence does show post-traumatic amnesia to be valid, and it probably remains
      the best simple prognostic item available. In clinical practice one should avoid
      placing too much weight on post-traumatic amnesia alone.

PMID- 9010399
TI  - Hydrodynamic properties of hydrocephalus shunts: United Kingdom Shunt Evaluation
      Laboratory.
AB  - BACKGROUND: Although about 80% of properly diagnosed patients with hydrocephalus
      improve after implantation of any model of shunt, the remaining 20% may develop
      further complications because of inadequate shunt performance. Therefore,
      hydrocephalus shunts require careful independent laboratory evaluation. METHOD:
      Computer supported shunt testing, based on the new International Standard
      Organisation directives, characterises various aspects of pressure-flow
      performance of shunts such as variability with time, susceptibility to reflux,
      siphoning, temperature related behaviour, external pressure, the influence of a
      strong magnetic field (for example, MRI), presence of pulsation in differential
      pressure, particles in drained fluid, etc. RESULTS: Seven different models of
      valves, representing most common constructions, have been tested so far. Most
      contemporary valves have a hydrodynamic resistance which is too low. This may
      result in overdrainage both related to posture and during nocturnal cerebral
      vasogenic waves. A long distal catheter increases the resistance of these valves
      by 100%-200%. Most shunts are very sensitive to the presence of air bubbles and
      small particles in drained fluid. Few shunt models offer reasonable resistance to
      negative outlet pressure, preventing complications related to overdrainage.
      Valves with an antisiphon device may be blocked by raised subcutaneous pressure.
      All programmable valves are susceptible to overdrainage in an upright position.
      CONCLUSION: The behaviour of a valve during such testing is of immediate
      relevance to the surgeon and may not be adequately described in the
      manufacturer's product information.

PMID- 9010400
TI  - Operational criteria for the classification of chronic alcoholics: identification
      of Wernicke's encephalopathy.
AB  - OBJECTIVES: To establish better operational criteria for the diagnosis of
      Wernicke's encephalopathy. Current criteria for diagnosing Wernicke's
      encephalopathy require the presence of three clinical signs (oculomotor
      abnormalities, cerebellar dysfunction, and an altered mental state), although it
      has often been reported that most patients do not fulfil all these criteria.
      METHODS: The clinical histories of 28 alcoholics with neurological and
      neuropsychological assessments and definitive neuropathological diagnoses were
      examined to determine clinical signs for use in a screening schedule. Operational
      criteria were then proposed for differentiating patients with Wernicke's
      encephalopathy alone or in combination with Korsakoff's psychosis or hepatic
      encephalopathy. The new criteria for Wernicke's encephalopathy require two of the
      following four signs; (1) dietary deficiencies, (2) oculomotor abnormalities, (3)
      cerebellar dysfunction, and (4) either an altered mental state or mild memory
      impairment. Reproducibility and validity testing of these criteria were performed
      on 106 alcoholics screened from a large necropsy sample. RESULTS: Despite rater
      variability with regard to specific symptoms, within and between rater
      reliability for diagnostic classification using the criteria retrospectively on
      patient records was 100% for three independent raters. Validity testing showed
      that Wernicke's encephalopathy was underrecognized only when occurring with
      hepatic encephalopathy (50% sensitivity). CONCLUSIONS: By contrast with current
      criteria, the proposed operational criteria show that the antemortem
      identification of Wernicke's encephalopathy can be achieved with a high degree of
      specificity.

PMID- 9010401
TI  - Influence of spinal cord injury on cerebral sensorimotor systems: a PET study.
AB  - OBJECTIVES: To assess the effect of a transverse spinal cord lesion on cerebral
      energy metabolism in view of sensorimotor reorganisation. METHODS: PET and 18F
      fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 11
      patients with complete paraplegia or tetraplegia after spinal cord injury and 12
      healthy subjects. Regions of interest analysis was performed to determine global
      glucose metabolism (CMRGlu). Statistical parametric mapping was applied to
      compare both groups on a pixel by pixel basis (significance level P = 0.001).
      RESULTS: Global absolute CMRGlu was lower in spinal cord injury (33.6 (6.6)
      mumol/100 ml/min (mean (SD)) than in controls (45.6 (6.2), Mann-Whitney P =
      0.0026). Statistical parametric mapping analysis disclosed relatively increased
      glucose metabolism particularly in the supplementary motor area, anterior
      cingulate, and putamen. Relatively reduced glucose metabolism in patients with
      spinal cord injury was found in the midbrain, cerebellar hemispheres, and
      temporal cortex. CONCLUSIONS: It is assumed that cerebral deafferentiation due to
      reduction or loss of sensorimotor function results in the low level of absolute
      global CMRGlu found in patients with spinal cord injury. Relatively increased
      glucose metabolism in brain regions involved in attention and initiation of
      movement may be related to secondary disinhibition of these regions.

PMID- 9010402
TI  - Is family history an independent risk factor for stroke?
AB  - OBJECTIVE: To estimate the influence of family history on the occurrence of
      stroke. METHODS: A case-control study was carried out from August 1992 to January
      1994. The study population comprised 502 patients with a first stroke, aged
      between 20 and 70 years, who were treated at 48 affiliated hospitals. The same
      number of age and sex matched controls were selected from outpatients. Diagnoses
      were based on CT findings and clinical signs. There were 155 case-control pairs
      for subarachnoid haemorrhage, 158 for intracerebral haematoma, and 159 for
      cerebral infarction. Information about the patients and their families was
      obtained from a questionnaire which included the family histories of each subtype
      of stroke and other potential risk factors for stroke. The data were analysed
      focusing on the role of the family histories in the occurrence of stroke.
      RESULTS: In univariate analysis, the family histories of subarachnoid haemorrhage
      and intracerebral haematoma were positively associated with each of the subtypes
      of stroke (odds ratios 11.24 for subarachnoid haemorrhage, 2.39 for intracerebral
      haematoma), whereas family history of cerebral infarction was not a significant
      risk factor for its occurrence (odds ratio 1.41). Family history of intracerebral
      haematoma was correlated with a personal history of hypertension and habitual
      alcohol consumption. After adjustment for potential risk factors (hypertension,
      diabetes, hyperlipidaemia, obesity, alcohol consumption, and regular smoking),
      family history of subarachnoid haemorrhage still remained the most powerful risk
      factor for subarachnoid haemorrhage, whereas family history of intracerebral
      haematoma no longer showed a significant association with haematoma. CONCLUSION:
      Genetic factors play a major part in the pathogenesis of subarachnoid
      haemorrhage, and family history of subarachnoid haemorrhage is the strongest
      independent risk factor for the disease. On the other hand, family history of
      intracerebral haematoma was not an independent risk factor for haematoma, but it
      might be a good predictor, which indirectly influences the pathogenesis of
      intracerebral haematoma via certain hereditary components such as hypertension,
      and even lifestyle factors such as alcohol consumption. In cerebral infarction,
      genetic factors play a minor part in its pathogenesis.

PMID- 9010403
TI  - Entrapment of motor nerves in motor neuron disease: does double crush occur?
AB  - OBJECTIVE: To investigate whether "diseased nerves" are more prone to entrapment
      neuropathy than normal nerves. Nerve conduction studies of human neuropathies
      have shown that electrophysiological abnormalities are often most prominent at
      potential sites of nerve entrapment, and entrapments are more common in patients
      with radiculopathies--a concept designated as "double crush". As entrapment
      neuropathies commonly occur in otherwise healthy subjects, it is unclear whether
      this relation is coincidental or whether peripheral nerves affected by disease
      are rendered more susceptible to effects of repeated minor trauma, traction, or
      mechanical compression. METHODS: Sequential ulnar nerve conduction studies were
      prospectively performed at baseline and at four, eight, and 12 month intervals in
      16 patients with amyotrophic lateral sclerosis. Ulnar nerve entrapment was
      defined as a focal reduction (> 10 m/s) in conduction velocity in the across
      elbow segment. RESULTS: Ulnar sensory and motor nerve fibres showed similar
      findings of ulnar nerve entrapment at baseline and at follow up over the period
      of the study. Nerves with ulnar nerve entrapment showed a significantly greater
      reduction in distal motor amplitudes than nerves without entrapment, even though
      distal ulnar sensory amplitudes remained unchanged. CONCLUSIONS: Motor nerves in
      motor neuron disease do not seem to be more susceptible to entrapment at the
      elbow than do healthy sensory nerves, thus casting doubt on the double crush
      hypothesis. Nerves with double pathology (amyotrophic lateral sclerosis and ulnar
      nerve entrapment), however, seem to undergo more rapid axonal loss than do nerves
      with single pathology (amyotrophic lateral sclerosis or ulnar nerve entrapment
      alone).

PMID- 9010404
TI  - Impairment and recovery of left motor function in patients with right hemiplegia.
AB  - OBJECTIVE: To assess the motor function of the left, supposedly unaffected, limbs
      of patients with an acute right vascular hemiplegia. METHODS: Fifteen patients
      with an acute vascular right hemiplegia and 16 matched healthy controls were
      studied. Motor function of the left limbs of each patient was evaluated on days
      20 and 90 after their stroke using four validated tools (hand dynamometer,
      isokinetic dynamometer, finger tapping, and nine hole peg test). RESULTS: There
      was a significant impairment of motor function of the left limbs of patients at
      day 20 compared with controls. The impairment had recovered almost completely at
      day 90 after the stroke. CONCLUSION: These results show the bilateral cerebral
      representation of the human motor system and suggest the participation of
      ipsilateral motor pathways in recovery after a stroke.

PMID- 9010405
TI  - Post-traumatic stress disorder and head injury as a dual diagnosis: "islands" of
      memory as a mechanism.
AB  - This case study describes post-traumatic stress disorder (PTSD) and head injury
      after a road traffic accident involving a pedestrian. Previous studies have
      proposed two mechanisms by which this dual diagnosis may occur: (1) when post
      traumatic amnesia and retrograde amnesia are small or non-existent and (2) when
      non-declarative memory systems for the traumatic event are in operation. This
      case study demonstrates a third mechanism--"islands" of memory within post
      traumatic amnesia.

PMID- 9010406
TI  - Neuromyelitis optica (Devic's syndrome): no association with the primary
      mitochondrial DNA mutations found in Leber hereditary optic neuropathy.
AB  - Devic's neuromyelitis optica is a rare syndrome characterised by the combination
      of acute or subacute optic neuritis and transverse myelitis, in some cases
      considered to be a variant of multiple sclerosis. Mutations of mitochondrial DNA
      (mtDNA) associated with Leber hereditary optic neuropathy (LHON) have been
      identified in some patients with multiple sclerosis in whom optic neuritis is a
      prominent early feature. Using restriction enzyme digestion of mtDNA products
      amplified by the polymerase chain reaction, the primary LHON mtDNA mutations at
      positions 3460 bp, 11,778 bp, and 14,484 bp have been excluded in four women with
      Devic's neuromyelitis optica. A mutation at 4160 bp associated in some LHON
      families with more widespread neurological disease was also not detected. It is
      concluded that the primary mtDNA mutations currently associated with LHON are not
      responsible for the prominence of optic nerve disease in Devic's neuromyelitis
      optica.

PMID- 9010407
TI  - High signal intensity on T1 weighted MRI of the anterolateral column of the
      spinal cord in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To investigate MRI abnormalities in patients with amyotrophic lateral
      sclerosis. METHODS: Fourteen patients with amyotrophic lateral sclerosis
      underwent MRI of the head and spinal cord using T1 and T2 weighted images. Forty
      age matched controls (29 with other neurological diseases, 11 with non
      neurological diseases) underwent MRI of the cervical spinal cord using T1 and T2
      weighted images. RESULTS: In all the control patients, the signal intensity of
      the posterior column was equal or slightly hypointense compared with the
      anterolateral column of the cervical spinal cord on T1 weighted images. However,
      eight of 14 patients with amyotrophic lateral sclerosis showed pronounced high
      signal intensity in the anterolateral column of the spinal cord on T1 weighted
      MRI, which also disclosed high signal intensity of the intracranial corticospinal
      tract in two of the 14 patients. T2 weighted MRI demonstrated high signal
      intensity of the lateral corticospinal tract of the spinal cord in two, high
      signal intensity of the intracranial corticospinal tract in five, and low signal
      intensity of the motor cortex in six of the 14 patients. Two of the 14 patients
      showed no abnormal findings on MRI. CONCLUSIONS: High signal intensity of the
      anterolateral column of the spinal cord of patients with amyotrophic lateral
      sclerosis is a new imaging abnormality and may be useful for the diagnosis of
      this disease.

PMID- 9010409
TI  - Pseudotumour cerebri syndrome due to cryptococcal meningitis.
AB  - Three cases are reported of the pseudotumour cerebri syndrome-that is,
      intracranial hypertension without mass lesion or enlarged ventricles, due to
      cryptococcal meningitis. In these patients the papilloedema was successfully
      treated with optic nerve sheath decompression, and the intracranial hypertension
      with lumboperitoneal CSF shunting. These cases support the concept that
      pseudotumour cerebri is a syndrome of intracranial hypertension that can be due
      to any disorder producing obstruction of the CSF pathways at the level of the
      arachnoid villi. This concept is important because it directs therapy to
      normalise the intracranial pressure and preserve vision.

PMID- 9010408
TI  - Correlation of MRI and neuropathology in AIDS.
AB  - OBJECTIVE: To assess the correlation between findings on radiological and
      neuropathological examinations of the brain. METHODS: The formalin fixed brains
      of 19 patients who had died of AIDS were examined by MRI and neuropathology.
      RESULTS: The rate of identification of cerebral atrophy was similar
      radiologically and neuropathologically. However, only in half of these cases were
      the two examinations concordant in the diagnosis. Furthermore, in the 15 brains
      which had radiological diffuse white matter lesions, the underlying pathology was
      heterogeneous. CONCLUSIONS: The possible reasons for the inconsistencies, and
      their relevance to the interpretation of imaging studies, are discussed. The
      study suggests that the qualitative identification of atrophy in the postmortem
      brain is problematical and that diffuse white matter lesions seen on MRI are not
      indicative of a specific pathological process.

PMID- 9010410
TI  - MRI appearances in subacute combined degeneration of the spinal cord due to
      vitamin B12 deficiency.

PMID- 9010411
TI  - Rapid neurological deterioration in a patient with multiple sclerosis treated
      with systemic interleukin-2 and interferon-alpha 2b for metastatic renal cell
      carcinoma.

PMID- 9010412
TI  - A rostrocaudal gradient of nitrate plus nitrite concentrations in CSF.

PMID- 9010413
TI  - Desirable properties for instruments assessing quality of life: evidence from the
      PDQ-39.

PMID- 9010414
TI  - How far are we in understanding the cause of Parkinson's disease?

PMID- 9010415
TI  - Classification of previously unclassified cases of craniosynostosis.
AB  - Cases of craniosynostosis usually fall into well-demarcated categories: those
      related to a syndrome or those identified by a combination of suture involvement
      and morphological appearance. Between 1976 and 1995, 53 (3.6%) of 1474 cases in
      the craniofacial databank were assessed and designated as nonsyndromic but
      unclassifiable. The records and radiological studies obtained in these patients
      were retrospectively analyzed and comparisons were made with patients classified
      in the databank as having simple craniosynostoses. It proved possible to divide
      the formerly unclassifiable cases into two groups: those with "two-suture
      disease" (Group A) and a "complex" group (Group B) in which more than two sutures
      were affected. Group A consisted of 36 cases (68%) of patients presenting with
      clear evidence of simultaneous involvement of two sutures but with no progression
      over time to suggest a more diffuse pansynostosis. Suture involvement was as
      follows: 17 of 36 sagittal plus one coronal; seven of 36 sagittal and metopic;
      six of 36 sagittal plus one lambdoid; and six of 36 metopic plus one coronal. The
      only significant difference between the Group A cases and the cases of simple
      craniosynostoses was in the percentage requiring a second operation (24% vs. 5%,
      p < 0.0001). Group B consisted of 17 cases in which the patients presented at a
      slightly earlier age (mean 1 year) with severe morphological changes and multiple
      suture involvement. At the time of surgery, six of 17 patients showed large areas
      of lacunae within the cranial vault, making craniectomy the only option. In Group
      B, 10 of 17 patients displayed bilateral lambdoid plus sagittal suture
      involvement resulting in marked occipital recession posteriorly, whereas
      anteriorly in six of these 10 patients there was a massive frontal bone
      associated with posteriorly located coronal sutures. In contrast, there were also
      four patients in Group B with bilateral coronal plus metopic involvement
      resulting in a small frontal bone. There was a trend toward a lower intelligence
      quotient and a worse morphological outcome in the patients in Group B, but again
      the only result attaining statistical significance when compared to the databank
      was the rate of second operation (37.5 vs. 5%, p < 0.0001). "Two-suture
      synostosis" is a relatively straightforward condition and is treatable with
      standard craniosynostosis techniques. However, possibly as a result of surgical
      compromise when two sutures are involved, the rate of reoperation is far higher
      than in simple suture cases. In contrast, patients in the "complex" group
      presenting with severe multisuture involvement require a more tailor-made
      approach to their management that often entails a second procedure.

PMID- 9010416
TI  - Skull base chordomas: a management challenge.
AB  - Because of their critical location, invasive nature, and aggressive recurrence,
      skull base chordomas are challenging and, at times, frustrating tumors to treat.
      Both radical surgical removal and high-dose radiation therapy, particularly
      proton beam therapy, reportedly are effective in tumor control and improve
      survival rates. The authors posit that these tumors are best treated with radical
      surgery and proton-photon beam therapy. During the last 5 years, they treated 25
      patients (15 females and 10 males) who harbored pathologically diagnosed skull
      base chordomas. The mean age of the patients was 38.4 years (range 8-61 years).
      Previous surgery or radiation therapy was performed at other institutions in
      seven and two patients, respectively. The authors performed 33 surgical
      procedures on 23 patients. Radical removal (defined as absence of residual tumor
      on operative inspection and postoperative imaging) was achieved in 10 patients;
      subtotal resection (defined as resection of > 90% of the tumor) was achieved in
      11 patients; and partial resection (defined as resection of < 90% of the tumor)
      was achieved in two patients. Radical surgical removal included not only the
      excision of soft-tumor tissue, but also extensive drilling of the adjacent bone.
      Adjuvant therapy consisted of postoperative combined proton-photon beam therapy
      (given to 17 patients and planned for one patient) and conventional radiation
      therapy (two patients); three patients received no adjunct therapy. To date, four
      patients have died. One patient who had undergone previous surgery and sacrifice
      of the internal carotid artery died postoperatively from a massive stroke; one
      patient died from adenocarcinoma of the pancreas without evidence of recurrence;
      and two patients died at 25 and 39 months of recurrent tumor. Permanent
      neurological complications included third cranial nerve palsy (one patient) and
      hemianopsia (one patient); radiation necrosis occurred in three patients. Of the
      21 patients followed for more than 3 months after surgery, 16 have had no
      evidence of recurrence and five (including the two mortalities noted above) have
      had recurrent tumors (four diagnosed clinically and one radiologically). The mean
      disease-free interval was 14.4 months. A longer follow-up period will, hopefully,
      support the early indication that radical surgical removal and postoperative
      proton-photon beam therapy is an efficacious treatment. The use of skull base
      approaches based on the tumor classification introduced in this paper is
      associated with low mortality and morbidity rates.

PMID- 9010417
TI  - Trigeminal neuralgia: a quantitative sensory perception threshold study in
      patients who had not undergone previous invasive procedures.
AB  - The authors investigated 28 patients with "idiopathic" trigeminal neuralgia who
      had undergone no previous invasive procedures; together these patients had a
      total of 50 affected trigeminal divisions. Quantitative sensory perception
      thresholds were measured before operation. Preoperative measurements in the
      affected divisions indicated raised thresholds for touch (von Frey filaments) and
      temperature, but not for pinprick or heat pain, in agreement with the findings of
      Nurmikko. Only the tactile threshold was also significantly affected in the
      unaffected divisions on the affected side. The authors discuss their findings in
      relation to the pathophysiology of trigeminal neuralgia, concluding that the
      origin of the condition is almost certainly central to the gasserian ganglion.

PMID- 9010418
TI  - Sensory effects of microvascular decompression in trigeminal neuralgia.
AB  - Nineteen patients with "idiopathic" trigeminal neuralgia, who had not undergone
      any previous interventional procedures, possessed a vessel or vessels compressing
      the preganglionic nerve root that was demonstrated by magnetic resonance
      tomographic angiography. Pain was relieved immediately in all of these patients
      after they underwent microvascular decompression without observed nerve damage.
      Although preoperative measurement of sensory perception thresholds showed
      elevations in the thresholds for touch (von Frey filaments) and warmth and
      coolness sensations, these thresholds normalized during the postoperative period.
      An apparent deficit in the pinprick (sharpness) sensation appeared
      postoperatively, but the deficit gradually regressed and completely disappeared
      by 1 year after surgery; this phenomenon may have been a statistical anomaly. The
      patients' pain disappeared immediately postoperatively and remained absent
      throughout the follow-up period. The authors conclude that damage to the nerve or
      nerve root is not essential for the relief of trigeminal neuralgia.

PMID- 9010419
TI  - Chronic electrical stimulation of the gasserian ganglion for the relief of pain
      in a series of 34 patients.
AB  - The use of an implanted system for chronic electrical stimulation of the
      gasserian ganglion for relief of facial pain was described in 1980 by Meyerson
      and Hakansson. Between 1982 and 1995, the senior author (R.R.T.) performed
      gasserian ganglion stimulation in 34 patients for the relief of chronic medically
      intractable facial pain. The etiology of pain was peripheral damage to the
      trigeminal nerve in 22 patients (65%), central (stroke) damage in seven (21%),
      postherpetic neuralgia in four (12%), and unclassifiable cause in one (3%). All
      patients received a trial of transcutaneous stimulation (Stage 1). Successful
      trials in 19 patients (56%) were followed by implantation of a permanent system
      (Stage II). Trial and postimplantation stimulation were deemed successful when
      there was a reduction of pain by at least 50% whenever the stimulator was on.
      Success rates varied from five (71%) of seven patients for central pain to five
      (23%) of 22 for peripheral pain and none (0%) of four for postherpetic neuralgia.
      The median follow-up duration in successful cases was 22.5 months. Infections
      occurred in seven patients, all of whom had undergone Stage II treatment.
      Infections were more frequent when the stimulating electrode from Stage I was
      left in place for Stage II (six [43%] of 14) than when completely new hardware
      was used and prophylactic antibiotic drugs were administered (one [20%] of five).
      Other complications included iatrogenic injury to the trigeminal nerve or
      ganglion in three cases (9%), transient diplopia in two (6%), increased pain in
      two (6%), and various technical problems in 10 (29%). It is concluded that pain
      of central origin (stroke) is the type most likely to be relieved by this
      procedure. This finding is new, as the few other clinical series reported to date
      contain no patients with this type of pain. The risk of infection seems to be
      lower when completely new hardware is used for Stage II and prophylactic
      antibiotic drugs are administered.

PMID- 9010420
TI  - Hypoglossal-facial nerve side-to-end anastomosis for preservation of hypoglossal
      function: results of delayed treatment with a new technique.
AB  - This report describes a new surgical technique to improve the results of
      conventional hypoglossal-facial nerve anastomosis that does not necessitate the
      use of nerve grafts or hemihypoglossal nerve splitting. Using this technique, the
      mastoid process is partially resected to open the stylomastoid foramen and the
      descending portion of the facial nerve in the mastoid cavity is exposed by
      drilling to the level of the external genu and then sectioning its most proximal
      portion. The hypoglossal nerve beneath the internal jugular vein is exposed at
      the level of the axis and dissected as proximally as possible. One-half of the
      hypoglossal nerve is transected: use of less than one-half of the hypoglossal
      nerve is adequate for approximation to the distal stump of the atrophic facial
      nerve. The nerve endings, the proximally cut end of the hypoglossal nerve, and
      the distal stump of the facial nerve are approximated and anastomosed without
      tension. This technique was used in four patients with long-standing facial
      paralysis (greater than 24 months), and it provided satisfactory facial
      reanimation, with no evidence of hemitongue atrophy or dysfunction. Because it
      completely preserves glossal function, the hemihypoglossal-facial nerve
      anastomosis described here constitutes a successful approach in patients with
      long-standing facial paralysis who do not wish to have tongue function
      compromised.

PMID- 9010421
TI  - Radiosurgery for cerebral AVMs in children and adolescents: the neurobehavioral
      outcome.
AB  - Eight patients, ranging in age from 9 to 18 years, were treated for arteriovenous
      malformations using gamma knife radiosurgery and were evaluated an average of 6
      years after treatment to record potential effects of radiosurgery on cognitive
      and neuropsychological performance. Tests for general intelligence, nonverbal
      intelligence, memory and its components, and attention performance were
      administered to patients and compared with test results of age-matched siblings
      or first cousins. No statistically significant difference was found between the
      performance of patients and controls in any of the tests administered.
      Additionally, a specially designed questionnaire completed by the patients, their
      parents, and their teachers revealed that the patients' emotional and relational
      behavior was stable and unchanged after treatment. No correlation was found
      between the neurocognitive test performance and the lesion volumes irradiated,
      but the lesion site was found to contribute to the type of deficit recorded after
      treatment. The less invasive nature of the radiosurgical approach, combined with
      the brevity or absence of hospitalization, presumably contributed to the patients
      successful physical, mental, and emotional recovery.

PMID- 9010422
TI  - Endovascular treatment of acutely ruptured and unruptured aneurysms of the
      basilar bifurcation.
AB  - The surgical treatment of basilar bifurcation aneurysms is difficult and the need
      for an alternative approach is frequently stated. To assess the efficacy and
      safety of endovascular treatment of aneurysms located at the basilar bifurcation,
      the authors prospectively studied angiographic results, clinical results, and
      complications in 31 patients treated with Guglielmi detachable coils (GDCs).
      Patients treated acutely after subarachnoid hemorrhage (SAH) were graded
      according to the Hunt and Hess classification and clinical outcome was determined
      at 1- and 6-month intervals according to the Glasgow Outcome Scale (GOS). There
      were 18 women and 13 men, ranging in age from 34 to 67 years (mean age 48 years).
      Twenty-three were treated acutely after SAH. Clinical Hunt and Hess grades at
      presentation were as follows: Grade I, six patients; Grade II, three; Grade III,
      11; Grade IV, two; and Grade V, one. The GOS score for the group of patients
      treated acutely was: GOS I, 18 patients; GOS II, III, and IV, one patient each;
      and GOS V, two patients. There were seven technical complications in this group,
      most often asymptomatic, but one patient died after aneurysm rupture during
      treatment and one had residual diplopia at 4 months. Eight patients were treated
      for incidental basilar bifurcation aneurysms. One technical complication with no
      neurological deficit occurred in this group of patients with incidental
      aneurysms. Immediate angiographic results were considered to be satisfactory in
      94% of patients, with complete obliteration in 42% and residual neck and dog ears
      in 52%. There was no bleeding episode after treatment during clinical follow-up
      periods ranging from 3 to 42 months (mean 15.5 months in 29 surviving patients).
      Angiographic results were available for 27 patients at 6 months and were as
      follows: 30% of the lesions were completely obliterated, 59% presented some
      residual neck, and 11% showed some opacification of the aneurysm sac. During the
      follow-up period of up to 42 months, a total of seven recurrences were noted,
      necessitating retreatment with GDCs in five patients. Endovascular treatment of
      basilar bifurcation aneurysms prevented rebleeding and could be performed without
      clinically significant complications in 94% of patients. Clinical results after
      SAH compared favorably with surgical series. Morphological results appear less
      satisfactory, and long-term angiographic follow-up review is mandatory to detect
      recurrences.

PMID- 9010424
TI  - Cerebral blood flow and temporal lobe epileptogenicity.
AB  - Long-term surface cerebral blood flow (CBF) monitoring was performed to test the
      hypothesis that temporal lobe epileptogenicity is a function of epileptic
      cortical perfusion. Forty-three bitemporal 2-hour periictal CBF studies were
      performed in 13 patients. Homotopic regions of temporal cortex maintained
      interictal epileptic cortical hypoperfusion and nonepileptic normal cortical CBF.
      At 10 minutes preictus, a statistically significant, sustained increase in CBF
      was detected on the epileptic temporal lobe. Two minutes preictus, there was
      approximation of CBF in the epileptic and nonepileptic temporal lobes.
      Thereafter, electrocorticographic (ECoG) and clinical seizure onset occurred. The
      linear relationship between CBF in the two hemispheres (epileptic and
      nonepileptic) was the inverse of normal (y = -0.347x + 62.767, r = 0.470, df =
      95, p < 0.05). The data indicated a direct linear correlation between epileptic
      cortical CBF and seizure interval (frequency-1), a clinical measure of
      epileptogenicity (r = 0.610, df = 49, p < 0.05). Epileptogenicity was also found
      to be a logarithmic function of the difference between nonepileptic and epileptic
      cortical perfusion (r = 0.564, df = 58, t = 5.20, p < 0.05). The results showed
      that progressive hypoperfusion of the epileptic focus correlated with a decreased
      seizure interval (increased epileptogenicity). Increased perfusion of the
      epileptic focus correlated with an increased seizure interval (decreased
      epileptogenicity). The fact that CBF alterations precede ECoG seizure activity
      suggests that vasomotor changes may produce electrical and clinical seizure
      onset.

PMID- 9010423
TI  - Reducing the risk of rebleeding before early aneurysm surgery: a possible role
      for antifibrinolytic therapy.
AB  - Previous studies on the initial nonoperative management of aneurysmal
      subarachnoid hemorrhage (SAH) demonstrated that antifibrinolytic therapy reduced
      the risk of rebleeding by approximately 50%; however, prolonged antifibrinolytic
      treatment was associated with an increase in the incidence of hydrocephalus and
      delayed ischemic deficit. When early surgical intervention became routine for
      ruptured aneurysms, the use of antifibrinolytic therapy diminished. However,
      early surgery is generally performed in the first several days after SAH and the
      risk of rebleeding remains until the aneurysm is obliterated. Based on a review
      of the literature, the authors formed two hypotheses: 1) the high-dose
      intravenous administration of epsilon-aminocaproic acid (EACA), an
      antifibrinolytic agent, might reduce the risk of recurrent hemorrhage in the
      interval between SAH and early surgical intervention, and 2) a short course of
      EACA might not produce the increase in complications previously associated with
      its prolonged administration. The use of preoperative high-dose EACA therapy was
      evaluated in 307 patients to determine its safety and efficacy in reducing the
      incidence of rebleeding before early aneurysm surgery. All patients were admitted
      within 3 days of their SAH and were classified as Hunt and Hess Grades I to III.
      Only four patients (1.3%) suffered a recurrent hemorrhage. This compares
      favorably to the rebleeding rate of 5.7% reported for the early surgery group in
      the International Cooperative Study on the Timing of Aneurysm Surgery. The
      incidence of hydrocephalus or symptomatic vasospasm was not unduly elevated in
      patients receiving preoperative EACA. Thirty-five patients (11.4%) needed
      temporary cerebrospinal fluid drainage during their hospitalization and, overall,
      8.8% required a ventriculoperitoneal shunt. The mean age of the patients who
      required a shunt was nearly 10 years older than the general study population.
      Seventy-one patients (23%) developed symptomatic vasospasm and 8.1% suffered a
      stroke. This study indicates that a brief course of high-dose EACA is safe and
      may be beneficial in diminishing the risk of rebleeding in good-grade patients
      prior to early surgical intervention. Further investigation is planned based on
      these promising results.

PMID- 9010425
TI  - Treatment of syringomyelia associated with arachnoid scarring caused by
      arachnoiditis or trauma.
AB  - The authors conducted a retrospective study of 107 patients treated for
      syringomyelia associated with arachnoid scarring between 1976 and 1995 at the
      Departments of Neurosurgery at the Nordstadt Hospital in Hannover, Germany, and
      the University of California in Los Angeles, California. Twenty-nine patients
      have not been surgically treated to date because of their stable neurological
      status. Seventy-eight patients with progressive neurological deficits underwent a
      total of 121 surgical procedures and were followed for a mean period of 32 (+/-
      37) months. All patients demonstrated arachnoid scarring at a level close to the
      syrinx. In 52 patients the arachnoid scarring was related to spinal trauma,
      whereas 55 had no history of trauma and developed arachnoid scarring was a result
      of an inflammatory reaction. Of these, 15 patients had undergone intradural
      surgery, eight had suffered from spinal meningitis, three had undergone peridural
      anesthesia, and one each presented with a history of osteomyelitis,
      spondylodiscitis, and subarachnoid hemorrhage. No obvious cause for the
      inflammatory reaction resulting in arachnoid scarring could be ascertained for
      the remaining 26 patients. The postoperative neurological outcome correlated with
      the severity of arachnoid pathology and the type of surgery performed. Shunting
      of the syrinx to the subarachnoid, pleural, or peritoneal cavity was associated
      with recurrence rates of 92% and 100% for focal and extensive scarring,
      respectively. Successful long-term management of the syrinx required
      microsurgical dissection of the arachnoid scar and decompression of the
      subarachnoid space with a fascia lata graft. This operation stabilized the
      preoperative progressive neurological course in 83% of patients with a focal
      arachnoid scar. For patients with extensive arachnoid scarring over multiple
      spinal levels or after previous surgery, clinical stabilization was achieved in
      only 17% with this technique.

PMID- 9010426
TI  - Cerebral hyperglycolysis following severe traumatic brain injury in humans: a
      positron emission tomography study.
AB  - Experimental traumatic brain injury studies have shown that cerebral
      hyperglycolysis is a pathophysiological response to injury-induced ionic and
      neurochemical cascades. This finding has important implications regarding
      cellular viability, vulnerability to secondary insults, and the functional
      capability of affected regions. Prior to this study, posttraumatic
      hyperglycolysis had not been detected in humans. The characteristics and
      incidence of cerebral hyperglycolysis were determined in 28 severely head injured
      patients using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET).
      The local cerebral metabolic rate of glucose (CMRG) was calculated using a
      standard compartmental model. In six of the 28 patients, the global cerebral
      metabolic rate of oxygen (CMRO2) was determined by the simultaneous measurements
      of arteriovenous differences of oxygen and cerebral blood flow (xenon-133).
      Hyperglycolysis, defined as an increase in glucose utilization that measures two
      standard deviations above expected levels, was documented in all six patients in
      whom both FDG-PET and CMRO2 determinations were made within 8 days of injury.
      Five additional patients were found to have localized areas of hyperglycolysis
      adjacent to focal mass lesions. Within the 1st week following the injury, 56% of
      patients studied had presumptive evidence of hyperglycolysis. The results of this
      study indicate that the metabolic state of the traumatically injured brain should
      be defined differentially in terms of glucose and oxygen metabolism. The use of
      FDG-PET demonstrates that hyperglycolysis occurs both regionally and globally
      following severe head injury in humans. The results of this clinical study
      directly complement those previously reported in experimental brain-injury
      studies, indicating the capability of imaging a fundamental component of cellular
      pathophysiology characteristic of head injury.

PMID- 9010427
TI  - The suboccipital cavernous sinus.
AB  - The authors studied the microsurgical anatomy of the suboccipital region,
      concentrating on the third segment (V3) of the vertebral artery (VA), which
      extends from the transverse foramen of the axis to the dural penetration of the
      VA, paying particular attention to its loops, branches, supporting fibrous rings,
      adjacent nerves, and surrounding venous structures. Ten cadaver heads (20 sides)
      were fixed in formalin, their blood vessels were perfused with colored silicone
      rubber, and they were dissected under magnification. The authors subdivided the
      V3 into two parts, the horizontal (V3h) and the vertical (V3v), and studied the
      anatomical structures topographically, from the superficial to the deep tissues.
      In two additional specimens, serial histological sections were acquired through
      the V3 and its encircling elements to elucidate their cross-sectional anatomy.
      Measurements of surgically and clinically important features were obtained with
      the aid of an operating microscope. This study reveals an astonishing anatomical
      resemblance between the suboccipital complex and the cavernous sinus, as follows:
      venous cushioning; anatomical properties of the V3 and those of the petrous
      cavernous internal carotid artery (ICA), namely their loops, branches, supporting
      fibrous rings, and periarterial autonomic neural plexus; adjacent nerves; and
      skull base locations. Likewise, a review of the literature showed a related
      embryological development and functional and pathological features, as well as
      similar transitional patterns in the arterial walls of the V3 and the petrous
      cavernous ICA. Hence, due to its similarity to the cavernous sinus, this
      suboccipital complex is here named the "suboccipital cavernous sinus." Its role
      in physiological and pathological conditions as they pertain to various clinical
      and surgical implications is also discussed.

PMID- 9010428
TI  - Progressive loss of glutamic acid decarboxylase, parvalbumin, and calbindin D28K
      immunoreactive neurons in the cerebral cortex and hippocampus of adult rat with
      experimental hydrocephalus.
AB  - The authors investigated functional neuronal changes in experimental
      hydrocephalus using immunohistochemical techniques for glutamic acid
      decarboxylase (GAD) and two neuronal calcium-binding proteins: parvalbumin (PV)
      and calbindin D28K (CaBP). Hydrocephalus was induced in 16 adult Wistar rats by
      intracisternal injection of a kaolin solution, which was confirmed
      microscopically via atlantooccipital dural puncture. Four control rats received
      the same volume of sterile saline. Immunohistochemical staining for GAD, PV, and
      CaBP, and Nissl staining were performed at 1, 2, 3, and 4 weeks after the
      injection. Hydrocephalus occurred in 90% of kaolin-injected animals with various
      degrees of ventricular dilation. In the cerebral cortex, GAD-, PV-, and CaBP
      immunoreactive (IR) interneurons initially lost their stained processes together
      with a concomitant loss of homogeneous neuropil staining, followed by the
      reduction of their total number. With progressive ventricular dilation, GAD- and
      PV-IR axon terminals on the cortical pyramidal cells disappeared, whereas the
      number of CaBP-IR pyramidal cells decreased, and ultimately in the most severe
      cases of hydrocephalus, GAD, PV, and CaBP immunoreactivity were almost entirely
      diminished. In the hippocampus, GAD-, PV-, and CaBP-IR interneurons demonstrated
      a reduction of their processes and terminals surrounding the pyramidal cells,
      with secondary reduction of CaBP-IR pyramidal and granular cells. On the other
      hand, Nissl staining revealed almost no morphological changes induced by ischemia
      or neuronal degeneration even in the most severe cases of hydrocephalus.
      Hydrocephalus results in the progressive functional impairment of GAD-, PV-, and
      CaBP-IR neuronal systems in the cerebral cortex and hippocampus, often before
      there is evidence of morphological injury. The initial injury of cortical and
      hippocampal interneurons suggests that the functional deafferentation from
      intrinsic projection fibers may be the initial neuronal event in hydrocephalic
      brain injury. Although the mechanism of this impairment is still speculative,
      these findings emphasize the importance of investigating the neuronal
      pathophysiology in hydrocephalus.

PMID- 9010430
TI  - Juvenile active ossifying fibroma. Report of four cases.
AB  - Juvenile active ossifying fibroma is a rare lesion seldom seen by neurosurgeons.
      It originates in the paranasal sinuses during childhood, grows slowly, and
      encroaches on adjacent orbital and cranial compartments. In the past 3 years,
      four patients with this lesion were seen (three men and one woman; mean age 28
      years). The clinical presentations were different with each patient: sinusitis,
      meningitis, periorbital pain, and a unique case of a juvenile active ossifying
      fibroma presenting with high-grade internal carotid artery stenosis and ischemic
      symptoms. Three patients were treated by transfacial approaches: two with a
      transfrontal-nasal approach and one with a transfrontal-nasoorbital approach. Two
      open resections resulted in gross-total excision and no recurrence as of the 2
      year follow-up review. In the third patient, the tumor-encased carotid artery was
      preserved at the expense of a complete resection; that patient underwent
      superficial temporal artery-middle cerebral artery bypass and remains without
      ischemic symptoms or tumor recurrence at 2 years. The fourth patient underwent
      three subtotal endoscopic resections and is also without symptomatic recurrence
      at 2 years. Three points must be made concerning these lesions. First, the
      clinical and radiographic characteristics of juvenile active ossifying fibroma
      may not be easily recognized by neurosurgeons, which could lead to misdiagnosis
      and mismanagement of these lesions. Second, this tumor can encase the carotid
      artery and cause severe stenosis or occlusion. Third, complete resection of the
      tumor is required to effect a cure, and transfacial approaches, which give wide
      exposure of the sinuses, appear to yield better, more radical resections than
      endoscopic procedures.

PMID- 9010429
TI  - Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin
      on cerebral blood flow, blood-brain barrier permeability, and cell survival in a
      rat model.
AB  - Recently, the authors showed that thrombin contributes to the formation of brain
      edema following intracerebral hemorrhage. The current study examines whether the
      action of thrombin is due to an effect on cerebral blood flow (CBF),
      vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo
      solutions of thrombin were infused stereotactically into the right basal ganglia
      of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability
      were measured. The actions of thrombin on vasoreactivity were examined in vitro
      by superfusing thrombin on cortical brain slices while monitoring microvessel
      diameter with videomicroscopy. In separate experiments C6 glioma cells were
      exposed to various concentrations of thrombin, and lactate dehydrogenase release,
      a marker of cell death, was measured. The results indicate that thrombin induces
      BBB disruption as well as death of parenchymal cells, whereas CBF and
      vasoreactivity are not altered. The authors conclude that cell toxicity and BBB
      disruption by thrombin are triggering mechanisms for the edema formation that
      follows intracerebral hemorrhage.

PMID- 9010431
TI  - Multiple neoplasms following craniospinal irradiation for medulloblastoma in a
      patient with nevoid basal cell carcinoma syndrome. Case report.
AB  - A 28-year-old man presented to the authors' hospital with multiple intracranial
      tumors. At 2 years of age, he had undergone resection of a medulloblastoma and
      received adjunctive craniospinal irradiation. Subsequently, he was diagnosed with
      nevoid basal cell carcinoma syndrome, Gorlin's syndrome. Since his first
      presentation, he has required surgery for multiple basal cell carcinomas, an
      osteochondroma of the rib, two meningiomas, a trigeminal schwannoma, and a
      pleomorphic liposarcoma, all of which arose within the radiation field. Despite
      this impressive list of benign and malignant neoplasms, the patient is relatively
      well and leads a normal life. The authors examine the relationships between
      Gorlin's syndrome and radiation therapy and the subsequent development of tumors.

PMID- 9010432
TI  - Disappearing cervical disc. Case report.
AB  - The authors report the case of a 48-year-old woman who experienced spontaneous
      resolution of a large herniated disc at C6-7. Spontaneous resolution of a
      herniated lumbar disc was first documented by computerized tomography. This case
      is another example of a rare spontaneous resolution of a cervical disc herniation
      documented by magnetic resonance imaging.

PMID- 9010433
TI  - Development of anterior cranial fossa dural arteriovenous malformation following
      head trauma. Case report.
AB  - Dural arteriovenous malformations (AVMs) are considered to be acquired lesions
      that develop secondary to venous obstruction, which sometimes happens in head
      trauma. However, there has been a report of an anterior cranial fossa dural AVM
      that occurred independently of a history of head trauma, and there has been
      speculation that these malformations are congenital. The authors recount their
      experience with a patient who had an anterior cranial fossa dural AVM that was
      discovered incidentally. The lesion was fed by the bilateral anterior ethmoidal
      arteries and drained into the superior sagittal sinus via frontal cortical veins.
      The patient had a history of severe head trauma that had occurred 30 years
      earlier. This is the first case report in which a previous head trauma is
      strongly believed to be the cause of an anterior cranial fossa dural AVM. The
      authors postulate that anterior cranial fossa dural AVMs can develop secondary to
      a head trauma.

PMID- 9010434
TI  - Mobilization of the internal carotid artery for basilar artery aneurysm surgery.
      Technical note.
AB  - The authors describe a technique for mobilization of the internal carotid artery
      (ICA) for basilar artery (BA) aneurysm surgery. Using the epidural approach, the
      anterior clinoid process, orbital roof, and optic canal are drilled away. The ICA
      is made mobile to the C3 segment by cutting the dural ring and dissecting the ICA
      from the carotid groove. The ophthalmic artery is then dissected from the optic
      canal. This mobilization of the ICA secures wide operative fields on both its
      medial and lateral sides and permits complete clipping of BA aneurysms.

PMID- 9010435
TI  - Decompression via microsurgical anterior foraminotomy for cervical spondylotic
      myelopathy. Technical note.
AB  - Over the past few years, a microsurgical anterior foraminotomy technique has been
      developed by the author and used to achieve spinal cord decompression for the
      treatment of cervical spondylotic myelopathy. A 5 x 8-mm unilateral anterior
      foraminotomy is accomplished by resecting the uncovertebral joint via an anterior
      approach. Through the foraminotomy hole, the posterior osteophytes at the spinal
      cord canal are removed diagonally up to the beginning of the contralateral nerve
      root. To treat multilevel disease, a tunnel is made among the foraminotomy holes.
      This technique accomplishes widening of the spinal cord canal in the transverse
      and longitudinal axes by direct resection of the compressive lesions through the
      holes of unilateral anterior foraminotomies; however, it does not require bone
      fusion or postoperative immobilization. Postoperatively patients remain in the
      hospital overnight, and do not need to wear cervical braces. This new surgical
      technique has shown excellent clinical outcomes with fast recovery and adequate
      anatomical decompression in patients with cervical spondylotic myelopathy. The
      surgical technique is reported and illustrated by two of the author's cases.

PMID- 9010436
TI  - Waveform changes due to conduction block and their underlying mechanism in spinal
      somatosensory evoked potential: a computer simulation. Technical note.
AB  - Based on a square-wave solid-angle analysis, a simplified mathematical model was
      produced for computing a sequence of potential change in a volume conductor
      generated by an impulse traveling along a nerve fiber. A conduction block was
      simulated as a phenomenon in which a depolarization wavefront stops traveling
      when it reaches a certain point, although the following repolarization wavefront
      continues to travel until it reaches the same point. The spinal somatosensory
      evoked potential (SSEP) was produced as an algebraic sum of simulated nerve fiber
      action potentials (NFAPs). With a conduction block, an NFAP that was normally
      triphasic showed a positive-negative diphasic wave with reduced negativity at the
      point of the block, diphasic waves with enhanced negativity at points immediately
      preceding the block, and initial-positive waves alone or abolition of any wave at
      points beyond the block. The absence of their terminal-positive phases
      paradoxically enhanced the negative peak of the spinal SSEPs in a partial block
      that involved only the constituent fastest fibers, because phase cancellation of
      the phases between the terminal-positive phases of the fastest fibers and the
      negative phases of the slower fibers, which normally happens, failed to occur. At
      the points immediately preceding the block, the identical mechanism sustained the
      spinal SSEP enhancement even when every fiber was included in the block. The
      computer model predicted that localization of the precise site of conduction
      block can be achieved by demonstrating an abrupt reduction in the amplitude of
      the spinal SSEP, which is accompanied by an increased negative wave caudally and
      an enhanced monophasic positive wave rostrally.

PMID- 9010437
TI  - Brachial plexus compression by venous aneurysms. Case illustration.

PMID- 9010438
TI  - Hydatid cyst and brain tumor in the same location. Case illustration.

PMID- 9010439
TI  - The suboccipital cavernous sinus.

PMID- 9010440
TI  - Functional magnetic resonance imaging.

PMID- 9010441
TI  - Traumatic subarachnoid hemorrhage.

PMID- 9010442
TI  - Embolization and radiosurgery for AVMs.

PMID- 9010443
TI  - Embolization and radiosurgery for AVMs.

PMID- 9010444
TI  - Central neurocytoma.

PMID- 9010445
TI  - New insights into insulin dependent diabetes mellitus from studies with
      transgenic mouse models.

PMID- 9010446
TI  - T cell adhesion to endothelial cells and extracellular matrix is modulated upon
      transendothelial cell migration.
AB  - During inflammation, T cells transmigrate from the bloodstream into perivascular
      tissues. As T cells transmigrate, they undergo a series of attachments to and
      detachments from the endothelium and then extravasate into the extracellular
      matrix (ECM). T cell migration into the ECM involves a number of mechanisms that
      influence cell-ECM interactions. The modulation of integrin expression and
      affinity are two such mechanisms in which cells can alter their ability to
      interact with other cells and ECM. We show in vitro that transmigrated T cells
      exhibit down-regulation of very late activation antigen-4 and leukocyte function
      associated antigen-1 integrin surface expression and a decrease in binding to
      recombinant vascular cell adhesion molecule-1 and recombinant intercellular
      adhesion molecule-1. Also, transmigrated T cells displayed an increase in binding
      to collagens I and IV and fibronectin. Further, brain sections of experimental
      autoimmune encephalomyelitis mice demonstrated that as T cells migrated farther
      into the tissue, very late activation antigen-4 expression was lost while CD4
      expression remained unchanged. The significance of these findings in the
      modulation of the inflammatory response is discussed.

PMID- 9010447
TI  - Characterization of a newly established human bone marrow endothelial cell line:
      distinct adhesive properties for hematopoietic progenitors compared with human
      umbilical vein endothelial cells.
AB  - Human bone marrow endothelial cells (HBMEC) are intimately involved in the homing
      of hematopoietic progenitor cells (HPC) to the bone marrow and in the regulation
      of proliferation and differentiation of these cells. Because availability of
      primary HBMEC and their capacity to be cultured in vitro are limited, we used
      isolated HBMEC to establish a cloned cell line by microinjection of a recombinant
      plasmid expressing simian virus 40 early genes under the control of a deletion
      mutant of the human vimentin promoter. Serum requirements for growth of a
      transformed HBMEC line (TrHBMEC) were markedly decreased compared with those of
      primary cells, and added growth factors were not required for proliferation.
      Cells took up acetylated low-density lipoprotein normally, bound to Ulex
      europaeus lectin, and stained positively for von Willebrand factor, P-selectin,
      CD31, CD34, CD44, very late antigen-5, and intercellular adhesion molecule-2
      (ICAM-2). After treatment with TNF-alpha or lipopolysaccharide, TrHBMEC increased
      surface expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and
      ICAM-1 in a manner similar to primary HBMEC. In contrast, IL-1 beta elicited much
      less up-regulation of these adhesion molecules than in primary cells. In previous
      work, we reported that, in a flow adhesion model, rolling of peripheral blood
      CD34+ cells on primary HBMEC was E-selectin-dependent, whereas VCAM-1 and ICAM-1
      contributed to firm adhesion. In the present study, we show that HPC adhere in a
      similar way to TrHBMEC. A less-pronounced role for VCAM-1 and ICAM-1 was found in
      the adhesion of HPC to human umbilical vein endothelial cells. Furthermore,
      significantly more CD34+ cells adhered to TNF-alpha-stimulated HBMEC and TrHBMEC
      than to similarly stimulated human umbilical vein endothelial cells. These data
      emphasize the importance of using microvessel HBMEC for studying the homing of
      HPC to the bone marrow, and indicate the usefulness of the above-described bone
      marrow endothelial cell line.

PMID- 9010448
TI  - Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate
      cancers and is inversely related to apoptosis.
AB  - Several oncogenes involved in prostate carcinogenesis activate mitogen-activated
      protein (MAP) kinases, which can relay both proliferative (via extracellular
      regulated kinases (ERK)) and apoptotic signals (via jun N-terminal protein
      kinases (JNK)) to the nucleus. Mitogen-activated protein kinase phosphatase 1
      (MKP-1) is induced by several oncogenes in the ras-dependent pathway and can
      inactivate both MAP kinase pathways. The role of MKP-1 in proliferation and
      apoptosis is, however, still controversial. A series of 51 prostate cancers,
      including a subset (n = 13) that had been previously treated by androgen
      ablation, was used to examine whether MKP-1 mRNA and protein expression
      correlated with that of ERK-1, JNK-1, bcl-2, which confers resistance to
      apoptosis, and apoptotic index measured by in situ end-labeling of fragmented
      DNA. In a subset of tumors, MKP-1 expression was assessed by semiquantitative RT
      PCR and was compared with both ERK-1 and JNK-1 enzymatic activity. In cases not
      treated by androgen ablation, MKP-1 was overexpressed in the preinvasive stage of
      prostate cancer, but its expression decreased with higher histologic grade and
      advanced disease stage. There was coexpression of MKP-1, ERK-1, and JNK-1
      proteins. In addition, MKP-1 expression was inversely correlated to JNK-1 but not
      to ERK-1 enzymatic activity. Finally, MKP-1 and bcl-2 were inversely related to
      apoptotic indices. In cases treated by total androgen ablation, MKP-1 and bcl-2
      were both down-regulated, whereas JNK-1 was up-regulated. Subpopulations of cells
      that did not undergo apoptosis maintained expression of both MKP-1 and bcl-2.
      These results suggest that MKP-1 overexpression is associated with the early
      phases of neoplastic transformation in prostate tissue. The enzymatic data on MKP
      1 kinase substrates and the inverse correlation between MKP-1 and parameters of
      programmed cell death support the hypothesis that MKP-1 inhibits apoptosis in
      human prostate tumors, perhaps through the JNK pathway.

PMID- 9010449
TI  - The role of active inducible nitric oxide synthase expression in the pathogenesis
      of capillary leak syndrome resulting from interleukin-2 therapy in mice.
AB  - Previously, we showed that nitric oxide (NO) plays a major role in the
      pathogenesis of IL-2-induced capillary leak syndrome in healthy or mammary
      adenocarcinoma-bearing C3H/HeJ mice. NO synthase (NOS) inhibitors, such as NG
      nitro-L-arginine methyl ester (L-NAME) reduced all the manifestations of IL-2
      induced capillary leakage, without compromising the antitumor effects of IL-2.
      The present study was carried out on healthy C3H/HeJ mice subjected to one or two
      4-day rounds of systemic IL-2 therapy with or without oral L-NAME therapy to: (a)
      identify the tissue source of NOS activity and NOS protein induced by IL-2
      therapy; (b) identify histologically the nature of the structural damage to the
      lungs associated with IL-2 therapy-induced pulmonary edema; and (c) evaluate the
      effects of additional L-NAME therapy on the above-mentioned parameters. Results
      revealed that IL-2 therapy in healthy mice resulted in the expression of
      inducible NOS in numerous tissues including the endothelium and muscles of the
      anterior thoracic wall as well as splenic macrophages. One round of IL-2 therapy
      resulted in high levels of inducible NOS (iNOS) activity in the anterior thoracic
      wall accompanied by pleural effusion. After two rounds of IL-2 therapy, there was
      neither pleural effusion nor high iNOS activity in the thoracic wall. IL-2
      induced pulmonary edema after one round of therapy correlated to both a
      significant rise in NO production measured in the serum and structural damage to
      the lungs and its capillaries. Addition of the NOS inhibitor L-NAME totally
      eradicated NOS activity but not necessarily iNOS expression. It also reduced IL-2
      induced pulmonary edema and pleural effusion, restrained the rise in the levels
      of NO metabolites (nitrites and nitrates) in the serum and pleural effusion, and
      significantly restored the structural integrity of the lungs after one round of
      therapy. Thus, NOS inhibitors may be beneficial adjuncts to IL-2 therapy for
      cancer and infectious diseases.

PMID- 9010450
TI  - A specific elevation of RANTES in bronchoalveolar lavage fluids of patients with
      chronic eosinophilic pneumonia.
AB  - Chronic eosinophilic pneumonia (CEP) is a rare, idiopathic lung disorder
      characterized pathologically by massive eosinophil infiltration into lung. In the
      bronchoalveolar lavage fluid (BALF) of patients with CEP, eosinophil numbers were
      markedly increased but returned to normal-levels upon the resolution of clinical
      symptoms, which suggests the crucial role of eosinophils in the pathogenesis of
      CEP. To clarify the mechanism of eosinophil accumulation in CEP, we determined
      the BALF levels of RANTES and macrophage inflammatory protein-1 alpha, two
      chemokines that predominantly exhibit in vitro eosinophil chemotactic activities.
      RANTES (106.7 +/- 27.2 pg/mg albumin; n = 16) concentrations in BALF from
      patients with CEP were significantly elevated in comparison with those of normal
      control subjects (1.4 pg/mg albumin; n = 13), whereas BALF macrophage
      inflammatory protein-1 alpha levels were not. In addition, eosinophils,
      lymphocytes, and macrophages in BALF were positively stained with a specific anti
      RANTES antibody, which suggests that RANTES was produced locally in the lungs of
      CEP patients. Moreover, BALF-RANTES levels correlated significantly with the
      proportion of eosinophils in BALF. Furthermore, nearly half of the eosinophil
      chemotactic activities in BALF were abrogated by the anti-RANTES antibody in
      vitro. Collectively, these data suggest that locally produced RANTES is involved
      in eosinophil accumulation in the pulmonary alveolus and interstitium of patients
      with CEP.

PMID- 9010452
TI  - Development of basophils in Mongolian gerbils: formation of basophilic cell
      clusters in the bone marrow after Nippostrongylus brasiliensis infection.
AB  - Development of basophilic leukocytes was studied in the Mongolian gerbil,
      Meriones unguiculatus, after infection with the nematode Nippostrongylus
      brasiliensis. After infection, peripheral blood basophilia developed and peaked
      at 2 weeks. In bone marrow sections, numbers of alcian blue+/safranine-
      basophilic cells were increased. These cells did not bind berberine sulfate and
      were clearly distinguishable from the bone marrow-resident mast cells, safranine+
      and berberine sulfate+. Alcian blue+/safranine- cells were identified by electron
      microscopy as basophilic myelocytes in various stages of maturation. In the early
      period of infection, these cells had round-to-oval granules with a homogenous
      electron-dense matrix, a well-developed Golgi apparatus and rough endoplasmic
      reticulum, and a nonsegmented nucleus. By enzyme cytochemical analysis, intense
      peroxidase activity was demonstrated in all of the specific granules as well as
      in the rough endoplasmic reticulum and Golgi apparatus. Two weeks after
      infection, the number of bone marrow basophilic cells further increased, forming
      distinct clusters or islands composed of up to 100 cells each. On electron
      micrographs, the basophilic cells in these clusters appeared to be late-stage
      basophilic myelocytes, ie, having an increased number of granules, a less
      conspicuous Golgi apparatus and rough endoplasmic reticulum, a horseshoe-shaped
      to-lobulated nucleus, and reduced peroxidase activity. Eosinophils and mast cells
      were rarely found in the basophilic cell clusters. Four weeks after infection,
      the clusters had disappeared. These results show that gerbil basophilic
      myelocytes tend to form cell clusters in the bone marrow during their active
      proliferation. The comparative paucity of other cell lineages in basophilic cell
      clusters suggests that basophilia is generated from differentiation/proliferation
      of precommitted basophil progenitors independently from cells of other lineages.

PMID- 9010451
TI  - Depletion of mitochondrial DNA, destruction of mitochondria, and accumulation of
      lipid droplets result from fialuridine treatment in woodchucks (Marmota monax).
AB  - Fialuridine (FIAU, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil) is
      toxic to liver, heart, muscle, and nerve in clinical trials for chronic viral
      hepatitis (CH). Mitochondrial toxicity was hypothesized. To address
      pathophysiologic mechanisms, we examined mitochondrial changes in FIAU-treated
      woodchucks (WC) with CH from woodchuck hepatitis virus infection. WC (with and
      without CH from woodchuck hepatitis virus infection) were treated with FIAU (1.5
      mg/kg/day) for 12 weeks. WC were killed. Liver, heart, skeletal muscle, and
      kidney samples underwent DNA extraction and were analyzed ultrastructurally
      (transmission electron microscopy). Myocardium, skeletal muscles, and liver
      samples were analyzed histologically. Abundance of hepatic, myocardial, muscle,
      and kidney mtDNA decreased in FIAU-treated WC, but the magnitude varied. mtDNA
      decreased 55% in heart, 65% in kidney, 74% in liver, and 87% in muscle (p < 0.02
      for each tissue: FIAU-treated versus FIAU-untreated). Cellular damage was
      characterized ultrastructurally by mitochondrial enlargement, cristae
      dissolution, and lipid droplets. Lipid droplets found in the heart, diaphragm,
      biceps, and liver were sufficient to identify FIAU-treated WC (p < 0.05 each).
      Widespread mitochondrial damage to many tissues resulted from chronic FIAU
      treatment and occurred irrespective of CH. It manifested with mtDNA depletion,
      intracytoplasmic lipid droplets, and destroyed mitochondrial cristae. Defective
      mtDNA replication with mtDNA depletion seems central to the subcellular
      pathophysiology of altered energy metabolism and multiorgan failure in FIAU
      toxicity.

PMID- 9010453
TI  - Apoptosis in keratinocytes is not dependent on induction of differentiation.
AB  - During embryological development and throughout life, regulation of the thickness
      of skin is likely to involve modulation of keratinocyte proliferation,
      differentiation, and cell death. One major mechanism of cell death is apoptosis;
      but the precise relationship between apoptosis and differentiation has not been
      well-defined. In this report, we demonstrate that when cultured undifferentiated
      keratinocytes have their adhesive interactions interrupted by either enzymatic
      treatment (ie, trypsin) and suspension in a semi-solid methyl cellulose medium,
      or exposure to antibodies against beta 1 integrins and E-cadherin, induction of
      differentiation occurs (expression of involucrin), as well as apoptosis (positive
      terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP-biotin nick end
      labeling (TUNEL) assay and DNA fragmentation). However, these events are not
      directly interdependent processes, as determined by two-color immunofluorescence
      staining. Thus, apoptosis can occur without evidence of differentiation and vice
      versa. The process o apoptosis in keratinocytes was dissected at the molecular
      level and found to be correlated with increased expression of Bax and decreased
      levels of Bcl-XL, with no role for either Bcl-2 or Bcl-XS. We conclude that
      keratinocytes do not need to undergo differentiation before undergoing apoptosis.

PMID- 9010454
TI  - Detection of clonality and genetic alterations in endometrial pipelle biopsy and
      its surgical specimen counterpart.
AB  - Carcinoma of the endometrium is the most frequently diagnosed gynecologic
      malignancy in the western world. Because endometrial carcinoma is monoclonal in
      origin, the small samples obtained in endometrial pipelle biopsies can be used in
      PCR clonal studies to distinguish cancerous from noncancerous lesions. The method
      used for clonal analysis was based on RFLP of the X chromosome-linked
      phosphoglycerokinase gene and random inactivation of one X chromosome by
      methylation in women. Among 50 endometrial pipelle biopsies, 26 (52%) were found
      to be heterozygous for the above-mentioned polymorphism. Of the samples taken
      from these informative (ie, heterozygous) patients, six were monoclonal including
      five cases of endometrial carcinoma and one of endometrial atypical hyperplasia.
      In each case, the same pattern of monoclonality was present in the surgical
      specimen counterpart. All of the remaining samples were polyclonal and, when the
      anatomical pathology data were contrasted, they correlated with nonmalignant
      endometrium (five secretory, five proliferative, seven atrophic, and three simple
      hyperplasias). In addition, genetic alterations study of monoclonal endometrial
      samples revealed a K-ras point mutation and a c-erbB2/neu gene amplification in
      two different endometrial carcinomas. Both alterations were also detected in the
      surgical specimens. In addition, a diagnosed set of 10 samples of simple
      hyperplasia and 5 of atypical hyperplasia were subjected to clonal assay. Among
      eight informative cases, the three that showed that showed the monoclonal pattern
      corresponded with cases of atypical hyperplasia. No other genetic alterations
      were detected in these samples. In conclusion, our data indicate that the
      detection of clonality in endometrial biopsy samples obtained by pipelle would be
      a useful application for the early diagnosis of endometrial cancer.

PMID- 9010455
TI  - Tissue-specific expression of interleukin-4 induces extracellular matrix
      accumulation and extravasation of B cells.
AB  - We have assessed the consequences of tissue-specific production of IL-4 by
      generating transgenic mice that express IL-4 under the control of the human
      insulin promoter in the Langerhans' islets of the pancreas. In these transgenic
      mice, designated Ins-IL-4 mice, we observed the deposition of extracellular
      matrix (ECM) around the islets beginning at an early age. This matrix was
      interspersed with eosinophils, macrophages, and fibroblasts; T cells were notably
      absent. As the mice aged, the exocrine tissue was steadily replaced by ECM and
      adipose tissue, and the pancreatic islets were disrupted by ECM deposition and
      newly formed pancreatic ducts. Most striking was the preferential accumulation of
      B lymphocytes around the blood vessels close to the islets. Vascular changes
      included induction of MadCAM (mucosal addressin cell adhesion molecule)-1, von
      Willebrand factor, and intercellular adhesion molecule-1 on endothelial cells in
      pancreata of Ins-IL-4 mice. Overall, tissue-specific expression of IL-4 induced a
      complex, localized host response that resulted in the excessive generation of ECM
      and the selective recruitment of inflammatory cells. These findings suggest that
      IL-4 has a role in (a) the regulation of potentially pathologic fibrotic events
      associated with chronic inflammatory lesions and (b) the recruitment of
      inflammatory cells in Th2 cell-dependent diseases such as allergic disorders.

PMID- 9010456
TI  - Cytokine-induced, nitric oxide-dependent, intracellular antirickettsial activity
      of mouse endothelial cells.
AB  - In a murine model of rickettsial disease in which, as in human rickettsioses,
      endothelial cells are the major target of infection, depletion of IFN-gamma or
      TNF-alpha converts a sublethal infection into a uniformly fatal disease with
      overwhelming rickettsial growth and decreased nitric oxide (NO) synthesis. The
      kinetics of NO production and rickettsial survival and growth were examined on
      Days 1, 2, and 3 after inoculation of endothelial cells with Rickettsia conorii
      under four different experimental conditions: (a) no cytokine treatment, (b)
      treatment with IFN-gamma and TNF-alpha, (c) treatment with cytokines and NG
      monomethyl-L-arginine, a competitive inhibitor of NO synthesis, and (d) treatment
      with sodium nitroprusside, a source of NO. Endothelial cells were examined for
      the presence of inducible nitric oxide synthase mRNA by specific reverse
      transcriptase-PCR after stimulation with IFN-gamma and TNF-alpha. Cytokine
      stimulated and unstimulated rickettsiae-infected endothelial cells were examined
      by electron microscopy to observe the cellular and rickettsial events.
      Transformed and diploid mouse endothelial cells stimulated by the combination of
      recombinant murine IFN-gamma and TNF-alpha killed intracellular Rickettsia
      conorii by a mechanism that required the synthesis of NO. The antirickettsial
      effect and NO synthesis were inhibited by treatment of endothelial cells with NG
      monomethyl-L-arginine. Addition of nitroprusside, which released NO, also exerted
      a strong antirickettsial effect in the absence of IFN-gamma and TNF-alpha.
      Endothelial inducible nitric oxide synthase mRNA was detected 4 hours after
      cytokine stimulation, increased substantially at 8 hours, and decreased to low
      levels by 72 hours. Ultrastructural evaluation revealed that endothelial cells
      effected rickettsial killing in association with autophagy. Double membranes of
      endothelial cell granular endoplasmic reticulum surrounded rickettsiae, which
      were also observed being destroyed within phagolysosomes. This study demonstrated
      for the first time that endothelial cells are capable of killing rickettsiae.
      When stimulated by the combination of IFN-gamma and TNF-alpha, mouse endothelial
      cells kill Rickettsia conorii by an NO-dependent mechanism. Within the
      endothelium, NO exerts a rickettsicidal effect.

PMID- 9010457
TI  - Modulation of E-cadherin expression in TPA-induced cell motility: well
      differentiated human adenocarcinoma cells move as coherent sheets associated with
      phosphorylation of E-cadherin-catenin complex.
AB  - We previously presented a two-dimensional cell motility assay using L-10, a
      highly metastatic variant of the human rectal adenocarcinoma cell line RCM-1, as
      a motility model of tumor cells of epithelial origin. In this model, L-10 cells
      moved outward from the cell islands mainly as a localized coherent sheet of cells
      when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA).
      Electronmicroscopic study of the migrating cell sheets revealed that wide
      intercellular gaps had developed at the lower portion of the cells, allowing them
      to extend leading lamellae, whereas close cell-cell contacts remained at the
      upper portion of the cells. In the present study, the mechanism involved in this
      localized modulation of cell-cell adhesion at the lower portion of the cells was
      investigated with special reference to E-cadherin expression. E-cadherin
      immunostaining, which was demonstrated using an anti-E-cadherin mAb, HECD-1, was
      decreased in migrating L-10 cell sheets. Apparently, however, E-cadherin was
      involved in the sheet formation of migrating cells because simultaneous or
      sequential treatment with TPA and HECD-1 inhibited sheet formation and caused
      scattering of migrating cells. With immunoelectron microscopic study, E-cadherin
      immunoreactivity was confined to the upper portion of migrating cells and lost at
      the lower portion. The level of E-cadherin and alpha-catenin expression was not
      altered by TPA treatment, although tyrosine phosphorylation of E-cadherin and
      catenins increased 1.6- to 1.9-fold. We propose that cells are released from cell
      cell adhesion only at the lower portion of the cells via phosphorylation of the E
      cadherin-catenin complex when stimulated with TPA. This change allows the cells
      to extend leading lamella and thus move together as coherent sheets (cohort
      migration).

PMID- 9010458
TI  - Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent and
      multiple point mutations in K-ras-2.
AB  - Hepatic angiosarcoma (HA) is an uncommon neoplasm associated with known etiologic
      factors in 25% to 42% of cases. It is, however, one of the most common sarcomas
      found in the liver. The aim of this study was to find was to find mutations in
      the K-ras-2 oncogene in sporadic and Thorotrast (TT)-induced HA. Point mutations
      in K-ras-2 were sought in archival, formalin-fixed tissue blocks from 24 patients
      with angiosarcoma. Of these, 19 cases were sporadic and 5 were TT-induced.
      Mutational analysis was performed by topographic microdissection with PCR
      amplification followed by genotyping. Specific mutations were determined by two
      independent methods: (a) direct sequencing of the PCR product confirmed by rePCR
      and by using a different sequencing primer, and (b) PCR-based selective
      enrichment of mutant DNA by endonuclease digestion followed by heteroduplex DNA
      analysis using denaturing gradient gel electrophoresis. Eleven K-ras-2 point
      mutations were detected in 7 of 24 (29%) tumors, including 5 of 19 (26%) sporadic
      HA and 2 of 5 (40%) TT-induced HA. There were seven G:C > A:T and four G:C > T:A
      mutations. All seven mutated tumors contained a codon 12-aspartate amino acid
      substitution. In addition, a second codon 12-cysteine mutant cell population was
      present in one of two codon 12-aspartate mutated TT-induced HA and in three of
      five codon 12-aspartate sporadic tumors. Of these four tumors, three contained
      both aspartate and cysteine mutations and were composed of multiple nodules; the
      fourth was a single mass. Seventeen tumors had multiple nodules; whereas 5 had a
      K-ras-2 mutation, 12 were wild-type. The molecular pathology of both sporadic and
      TT-induced HA is characterized by a high rate of K-ras-2 mutations characteristic
      of oxidative damage (ie, G:C > A:T and G:C > T:A mutations) resulting in two
      mutated population sets: codon 12 GGT > GAT and GGT > TGT (glycine to aspartic
      acid and cysteine). This is, to date, the first study to characterize the K-ras-2
      gene mutations within human sporadic and TT-induced HA by direct sequence
      analysis and denaturing gradient gel electrophoresis. These data further support
      the hypothesis linking adduct-forming vinyl chloride exposure to HA containing a
      much higher frequency of K-ras-2 mutations and a mutational spectrum
      characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl
      chloride.

PMID- 9010459
TI  - Internal tissue displacement measurement based on ultrasonic wave Doppler signal
      digital detection and its application to fetal movement monitoring.
AB  - We have developed a fetal movement monitoring system based on small displacement
      measurement of internal tissues. When ultrasonic pulses are transmitted to the
      fetus, the reflected ultrasonic waves which have a Doppler frequency shift due to
      the fetal movements are detected by using an ultrasonic pulsed Doppler technique.
      In this paper, we propose a displacement measurement method for internal tissues
      which is based on the Doppler signal digital detection technique. In the method,
      the received ultrasonic RF signals are sampled with a sampling frequency of four
      times higher than the centre frequency of the ultrasonic waves; the Doppler
      frequency shift signals are derived using digital signal processing. From the
      detected signals, the internal displacements are estimated using the arc-tangent
      method. The basic algorithm of the detection method has already been used in the
      area of blood flow sensing, however, we apply the algorithm to the displacement
      measurement of internal tissues. The comparison between the proposed method and
      the conventional method is presented. The fetal movement quantitative monitoring
      system based on the method which has been constructed is shown.

PMID- 9010460
TI  - An ultrasonic method for measuring the elastic properties of human tibial
      cortical and cancellous bone.
AB  - Ultrasonic techniques have been used to measure the elastic properties of bone.
      Eight human tibiae were used to determine and map the elastic properties of
      cortical and cancellous bone. The present study shows cortical bone to be at
      least orthotropic in its material symmetry. The mechanical properties of cortical
      bone are more homogeneous along the length than around the circumference. The
      variations in the properties around the quadrant of cortical bone are small, less
      than 10%, while differences in the properties around the circumference of
      cancellous bone are more apparent, approximately 5 times those of cortical bone.
      The elastic properties of cancellous bone exhibited inhomogeneity and some
      consistency pattern along both the length and the circumference.

PMID- 9010461
TI  - An investigation of the measurement of broadband ultrasonic attenuation in
      trabecular bone.
AB  - Commercial devices for the ultrasonic characterisation of bone normally report
      the broadband ultrasonic attenuation (BUA). This is the slope of the attenuation
      against frequency in some part of the frequency range 200-1000 kHz. The
      assumption is that the relationship is linear and hence independent of the
      frequency range selected. In this study the ultrasonic attenuation in the
      frequency range 200 to 800 kHz was measured with a variety of transducers in ten
      trabecular heel bone samples from elderly cadavers, assumed to be osteoporotic.
      The results indicate that the attenuation fits better to a second order
      polynomial function of frequency, than to the linear fit. The use of a straight
      line fit is only satisfactory in the higher frequency ranges (above 400 kHz). The
      use of lower frequencies results in a significant measurement error caused by the
      combination of a poor signal to noise ratio and the departure from linearity and
      this is greatest for samples with low attenuation. In the worst cases this can
      amount to a 30% discrepancy between the BUA values measured over different
      frequency ranges.

PMID- 9010463
TI  - Localization of endogenous furin in cultured cell lines.
AB  - Furin is a dibasic endopeptidase responsible for the proteolytic maturation of
      many precursor proteins in the secretory and endocytic pathways of mammalian
      cells. The levels of furin expression in most cells are very low, and this has
      hampered attempts to identify the intracellular compartments in which endogenous
      furin is localized. We have used a specific antibody reagent to a sequence in the
      carboxy terminus of furin to perform immunofluorescent staining of mammalian cell
      lines. This antibody was sensitive enough to detect staining for furin in various
      cell lines. For the most part, furin staining was confined to a juxtanuclear
      structure characteristic of the Golgi complex. Analyses by video microscopy and
      confocal microscopy showed that the distribution of furin was distinct from that
      of mannosidase II, a marker of the Golgi stack, and most closely resembled that
      of TGN38, a marker of the trans-Golgi network. Therefore, our results suggest
      that endogenous furin is predominantly localized to the area of the Golgi
      complex, most likely within the trans-Golgi network.

PMID- 9010464
TI  - Demonstration of apoptotic cells in tissue sections by in situ hybridization
      using digoxigenin-labeled poly(A) oligonucleotide probes to detect thymidine-rich
      DNA sequences.
AB  - The recognition of apoptotic cells by morphological appearance alone may be
      difficult. We have investigated the use of in situ hybridization (ISH) with
      digoxigenin-labeled poly(A) probes to detect apoptotic cells in tissue sections.
      This method was compared to conventional morphologic assessment and in situ end
      labelling (ISEL) in a range of tissues in which apoptosis is known to occur. ISH
      with poly(A) probes detected apoptotic nuclei in all tissues in which there was
      evidence of apoptosis as judged by conventional histology. ISH and, to a lesser
      extent, ISEL preferentially labeled shrunken but still intact nuclei with
      margination of chromatin, presumably at an early stage of apoptosis. The poly(A)
      hybridization was abolished by pretreatment of tissue sections with DNAse. After
      denaturation of DNA, poly(A) hybridized to nuclei in all cells. No convincing
      hybridization signal was detected in alcohol-fixed or fresh-frozen sections. Both
      ISEL and ISH labeled some of the nuclei in ischemic tissues. ISH with poly(A)
      oligonucleotide probes offers a simple alternative to ISEL for detection of cells
      in early stages of apoptosis. These probes hybridize to thymidine-rich sequences
      of DNA in the highly repeated Alu sequences within the nuclear genome. These
      sequences are believed to become available for hybridization after formalin
      fixation and paraffin embedding as a result of the apoptosis-related increase in
      the susceptibility of nuclear DNA to denaturation.

PMID- 9010465
TI  - Ultrastructural immunogold localization of osteopontin in human gastric mucosa.
AB  - We performed ultrastructural immunogold localization of osteopontin in the mucosa
      of human stomach. This adhesive glycoprotein was present in mucous and chief
      cells of the epithelial layer and in macrophages in the lamina propria. Parietal
      and endocrine cells of the epithelial layer and mast cells and plasma cells in
      the lamina propria did not contain osteopontin, serving as internal negative
      controls. Subcellular localizations of osteopontin included secretory granules
      and synthetic organelles in mucous and chief cells and phagolysosomes in
      macrophages. Extracellular concentrations of osteopontin were present in the
      glycocalyx and in an electron-lucent band between epithelial surface cells and
      the gastric lumen. Paracellular edema between the epithelium of the same cells
      was devoid of osteopontin. Immunogold localization of pepsinogen II was done to
      identify cells with mixed granule populations and contents of multicompartmental
      secretory granules. These studies revealed mucous cell granules and chief cell
      granules, each containing compartmentalized storage products, which included
      osteopontin and mucigen in mucous cells and osteopontin and pepsinogen II in
      chief cells. Cytochemical controls for the immunogold localizations were
      negative. The subcellular distribution of osteopontin in human gastric mucosa
      suggests possible roles for this glycoprotein in barrier function, host defense,
      and/or secretion.

PMID- 9010466
TI  - Carbonic anhydrase isoenzymes I, II, III, and IV are present in human esophageal
      epithelium.
AB  - Carbonic anhydrase (CA) isoenzymes have been widely studied in the
      gastrointestinal tract, where they mediate membrane transport events and pH
      regulation. However, the esophagus has generally received scant attention. In an
      immunohistochemical study confirmed by Western blotting, we have detected for CA
      isoenzymes (CAI, II, III, and IV) in the epithelium of human esophagus.
      Isoenzymes I, III, and sometimes IV (< 10%) were present in the cytoplasm of
      basal cells and II and IV in the cytoplasm and cell surface membranes,
      respectively, of suprabasal cells (prickle cells). The localization of CAIV to
      the plasma membranes was confirmed by electron microscopic immunocytochemistry.
      CA was effectively divided at the basal-suprabasal interface between low-activity
      CAI and III (basal) and high-activity CAII and IV (suprabasal). Carbonic
      anhydrase in esophageal epithelial cells may have several functions: elimination
      of CO2 and metabolites, participation in membrane transport events during active
      cell growth, and pH regulation as a protective mechanism against acidic gastric
      reflux.

PMID- 9010467
TI  - Tissue distribution and subcellular localization of rabbit liver
      metalloendopeptidase.
AB  - We have previously isolated rabbit liver microsomal metalloendopeptidase (MEP) as
      a candidate for the processing enzyme of vitamin K-dependent plasma proteins. A
      cDNA coding for MEP has revealed that it is structurally related to
      metalloendopeptidase-24.15, which catalyzes the proteolytic processing of several
      bioactive peptides. In this study we examined the tissue distribution and
      subcellular localization of MEP by light and electron microscopic
      immunohistochemical methods, in addition to Northern blot analysis. Chicken
      polyclonal antibodies were raised by using synthetic peptides AG1 (Met31-Asn46)
      and AG3 (Asp537-Gly551) derived from the sequence of MEP. Both anti-AG1 and anti
      AG3 antibodies reacted specifically with MEP, as judged by Western blotting and
      immunohistochemical methods. Both antibodies gave an identical staining
      distribution, which was localized on the luminal cell surfaces and in the
      cytoplasm of the following organs: liver, brain, lungs, kidneys, esophagus,
      stomach, duodenum, pancreas, placenta, epididymis, uterus, ovary, and oviduct.
      Northern blot analysis revealed that the expression of MEP mRNA is similar to its
      immunohistochemical distribution except in the heart. These results suggest that
      MEP may participate more closely in a degradation role in peptide metabolism in
      various tissues than in a processing role of the proprotein, like
      metalloendopeptidase-24.15.

PMID- 9010468
TI  - DNA staining for fluorescence and laser confocal microscopy.
AB  - We examined five nucleic acid binding fluorescent dyes, propidium iodide, SYBR
      Green I, YO-PRO-1, TOTO-3, and TO-PRO-3, for nuclear DNA staining, visualized by
      fluorescence and laser confocal microscopy. The optimal concentration, co
      staining of RNA, and bleaching speeds were examined. SYBR Green I and TO-PRO-3
      almost preferentially stained the nuclear DNA, and the other dyes co-stained the
      cytoplasmic RNA. RNAse treatment completely prevented the cytoplasmic RNA
      staining. In conventional fluorescence microscopy, these dyes can be used in
      combination with fluorescence-labeled antibodies. Among the dyes tested, TOTO-3
      and TO-PRO-3 stained the DNAs with far-red fluorescence under red excitation.
      Under Kr/Ar-laser illumination, TOTO-3 and TO-PRO-3 were best suited as the
      nuclear staining dyes in the specimens immunolabeled with fluorescein and
      rhodamine (or Texas red).

PMID- 9010469
TI  - Detection of mitochondrial DNA deletions in human skin fibroblasts of patients
      with Pearson's syndrome by two-color fluorescence in situ hybridization.
AB  - Pearson's marrow/pancreas syndrome is a disease associated with a large
      mitochondrial DNA (mtDNA) deletion. The various tissues of a patient contain
      heteroplasmic populations of wild-type (WT) and deleted mtDNA molecules. The
      clinical phenotype of Pearson's syndrome is variable and is not correlated with
      the size and position of the deletion. The histo- and cytological distribution of
      WT and deleted mtDNA molecules may be factors that correlate with the
      phenotypical expression of the disease. Here we introduce a new application of
      two-color FISH to visualize WT and deleted mtDNA simultaneously in a cell
      population of in vitro cultured skin fibroblasts of two patients with Pearson's
      syndrome. At the third passage of culturing, fibroblasts showed a remarkable
      heterogeneity of WT and deleted mtDNA: about 90% of the cells contained almost
      100% WT mtDNA, and 10% of the cells contained predominantly deleted mtDNA. At the
      tenth passage of culturing, fibroblasts showed a reduction of intercellular
      heteroplasmy from 10% to 1%, while intracellular heteroplasmy was maintained.
      This new approach enables detailed analysis of distribution patterns of WT and
      deleted mtDNA molecules at the inter- and intracellular levels in clinical
      samples, and may contribute to a better understanding of genotype-phenotype
      relationships in patients with mitochondrial diseases.

PMID- 9010470
TI  - Analysis of localization of adult T-cell leukemia-derived factor in the transient
      ischemic rat retina after treatment with OP-1206 alpha-CD, a prostaglandin E1
      analogue.
AB  - Prostaglandin E1 (PGE1) is commonly used in therapy for obstructive diseases,
      including ischemic retinopathy, in which pathogenetic reactive oxygen
      intermediates are responsible. However, the mechanism(s) of PGE1 in reducing
      tissue damage is still unclear. Adult T-cell leukemia-derived factor/human
      thioredoxin (ADF) is induced by oxidative stresses and has protective activity
      against oxidative cellular injury. To evaluate the possible involvement of ADF in
      the tissue-protective effect of PGE1, we analyzed ADF expression
      immunohistochemically using a rat transient retinal ischemia model. Rats were
      treated orally with 300 micrograms/kg/day OP-1206 alpha-cyclodextrin clathrate
      (OP-1206), a stable PGE1 analogue, for 14 days after photodynamic retinal
      vascular thrombosis by rose Bengal. Rats without any OP-1206 treatment were used
      as controls. In the OP-1206-treated rats, minimal retinal atrophy due to
      ischemia/reperfusion was observed histologically up to 14 days, whereas in the
      non-treated rats the inner layer of the retina became markedly atrophic. In
      parallel with the histological change, after 14 days following thrombosis ADF
      immunoreactivity was preserved on retinal pigment epithelial cells in the OP-1206
      treated rats, whereas it was diminished in the non-treated rats. These findings
      suggest an important role for ADF in the OP-1206-dependent suppression of retinal
      tissue damage caused by oxidative insult.

PMID- 9010471
TI  - Immunohistological localization and expression of alpha-actin in the baboon
      (Papio anubis) corpus luteum.
AB  - We have recently shown the presence of E-cadherin and of alpha- and gamma
      catenins in human and baboon corpora lutea. These are components of adherens
      junctions between cells. The cytoplasmic catenins link the cell membrane
      associated cadherins to the actin-based cytoskeleton. This interaction is
      necessary for the functional activity of the E-cadherins. Our aim therefore was
      to determine the presence of alpha-actin in the baboon corpus luteum, to further
      establish whether the necessary components for E-cadherin activity are present in
      this tissue. An antibody specific for the smooth muscle isoform of actin, alpha
      actin, was used for these studies. The results using immunohistochemistry show
      that (a) alpha-actin is present in steroidogenic cells of the active corpus
      luteum, theca externa of the corpus luteum, cells of the vasculature, and the
      tunica albuginea surrounding the ovary. The intensity of immunoreactivity for
      alpha-actin varied, with the cells of the vasculature reacting more intensely
      than the luteal cells. A difference in intensity of immunoreactivity was also
      observed among the luteal cells, with the inner granulosa cells showing stronger
      immunoreactivity than the peripheral theca lutein cells. There was no detectable
      immunoreactivity in the steroidogenic cells of the atretic corpus luteum.
      However, in both the active and atretic corpora lutea, alpha-actin-positive
      vascular cells were dispersed within the tissue. (b) Total alpha-actin (luteal
      and non-luteal), as determined by Western blot analyses, does not change during
      the luteal phase and subsequent corpus luteum demise (atretic corpora lutea). (c)
      hCG stimulated the expression of alpha-actin and progesterone secretion by the
      early luteal phase (LH surge + 1-5 days) and mid-luteal phase (LH surge + 6-10
      days) cells in culture, but only progesterone in the late luteal phase (LH surge
      + 11-15 days). The data show that alpha-actin is present in luteal cells and that
      its expression is regulated by hCG, thus suggesting that E-cadherin may form
      functional adherens junctions in the corpus luteum.

PMID- 9010472
TI  - Expression of HGF, its receptor c-met, c-myc, and albumin in cirrhotic and
      neoplastic human liver tissue.
AB  - Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately
      260,000 new cases each year, and liver cirrhosis is generally considered a major
      predisposing factor for HCC. However, specific changes of gene expression in
      liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte
      growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and
      albumin was analyzed. Gene expression was studied by PCR in seven normal human
      livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two
      cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed
      by immunofluorescent staining. HGF mRNA was not expressed in normal livers but
      was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded
      and fresh-frozen tissue samples yielded similar results. Immunohistochemical data
      correlated with PCR results regarding the overexpression of the HGF/c-met system
      in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent
      with altered function of tumor hepatocytes. The elevated expression of the HGF/c
      met system in HCC may play a role in tumor development and/or progression. Tissue
      localization studies of HGF and its receptor c-met protein support the existence
      of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a
      paracrine mechanism in normal liver.

PMID- 9010473
TI  - Immunofluorescence detection of F-actin on low melting point wax sections from
      plant tissues.
AB  - We developed a simple and reliable technique for immunofluorescence detection of
      F-actin on microtome sections of plant tissues. For the first time, large numbers
      of plant cells from various tissues that pass through their developmental stages
      could be consistently visualized on one section from plant organs. n
      Maleimidobenzoic acid N-hydroxysuccinimide ester-pretreated and formalin-fixed
      segments of plant roots and shoots were embedded in low melting point ester wax
      at 37C and sectioned on a microtome. After dewaxing and rehydration,
      microfilaments were visualized by indirect immunofluorescence technique with a
      monoclonal anti-actin antibody. The technique has been successfully used for
      visualization of tissue- and development-specific F-actin arrays in cells of Zea
      mays and Lepidium sativum root tips and of maize stem nodes.

PMID- 9010474
TI  - A new fluorescence reaction in DNA cytochemistry: microscopic and spectroscopic
      studies on the aromatic diamidino compound M&B 938.
AB  - We describe the fluorescence properties and cytochemical applications of the
      aromatic diamidine M&B 938. Treatment of cell smears (chicken blood, Ehrlich
      ascites tumor, rat bone marrow, mouse mast cells, and Trypanosoma cruzi
      epimastigotes) with aqueous solutions of M&B 938 (0.5-1 microgram/ml at pH 6-7;
      UV excitation) induced bright bluish-white fluorescence in DNA-containing
      structures (interphase and mitotic chromatin, AT-rich kinetoplast DNA of T.
      cruzi), which was abolished by previous DNA extraction. DNA was the unique
      fluorescent polyanion after staining with M&B 938 at neutral or alkaline pH,
      other polyanions such as RNA and heparin showing no emission. M&B 938-stained
      mouse metaphase chromosomes revealed high fluorescence of the AT-rich centromeric
      heterochromatin, and strong emission of heterochromatin in human chromosomes 1,
      9, 15, 16, and Y was found after distamycin A counterstaining. On agarose gel
      electrophoresis, M&B 938-stained DNA markers appeared as fluorescent bands. The
      1.635-KBP fragment from DNA ladder revealed a higher emission value than that
      expected from linear regression analysis. Spectroscopic studies showed
      bathochromic and hyperchromic shifts in the absorption spectrum of M&B 938
      complexed with DNA, as well as strong enhancement of fluorescence at 420 nm. In
      the presence of poly(dA)-poly(dT), the emission of M&B 938 was 4.25-fold higher
      than with DNA; no fluorescence was observed with poly(dG)-poly(dC). Experimental
      results and considerations of the chemical structure suggest that the minor
      groove of AT regions of DNA could be the specific binding site for M&B 938, which
      shows interesting properties and useful applications as a new DNA fluorochrome.

PMID- 9010475
TI  - In situ hybridization analysis of ZPK gene expression during murine
      embryogenesis.
AB  - ZPK is a recently described protein serine/threonine kinase that has been
      originally identified from a human teratocarcinoma cell line by the polymerase
      chain reaction and whose function in signal transduction has not yet been
      elucidated. To investigate the potential role of this protein kinase in
      developmental processes, we have analyzed the spatial and temporal patterns of
      expression of the ZPK gene in mouse embryos of different gestational ages.
      Northern blot analysis revealed a single mRNA species of about 3.5 KB from Day 11
      of gestation onwards. In situ hybridization studies demonstrated strong
      expression of ZPK mRNA in brain and in a variety of embryonic organs that rely on
      epitheliomesenchymal interactions for their development, including skin,
      intestine, pancreas, and kidney. In these tissues, the ZPK mRNA was localized
      primarily in areas composed of specific types of differentiating cells, and this
      expression appeared to be upregulated at a time concomitant with the onset of
      terminal differentiation. Taken together, these observations raise the
      possibility that the ZPK gene product is involved in the establishment and/or
      maintenance of a fully cytodifferentiated state in a variety of cell lineages.

PMID- 9010476
TI  - In situ localization of two fibrillar collagens in two compact connective tissues
      by immunoelectron microscopy after cryotechnical processing.
AB  - Two fibrillar collagens, the worm cuticular collagen and the vertebrate Type I
      fish scale collagen, both organized in a compact tissue, were localized by
      immunogold electron microscopy in resin sections after freeze-fixation and freeze
      substitution. Identification of these two fibrillar collagens failed with the use
      of postembedding labelling after conventional electron microscopic processing.
      Positive labeling of the Type I collagen was observed in sections of fish scales
      freeze-fixed by either slam-freezing or high-pressure freezing, freeze
      substituted in acetone with or without osmium tetroxide, and embedded in LR
      White. The worm cuticular collagen was detected in sections of cuticle that were
      freeze-fixed, freeze-substituted (necessarily with osmium tetroxide added to
      acetone), and embedded in either LR White or Epon. It was also detected in
      specimens pre-fixed by aldehydes before freeze-fixation. The Type I fish scale
      collagen appears to be more sensitive than the fibrillar cuticular collagen of
      worms to the procedures employed for postembedding immunoelectron microscopy. Our
      results have shown that freeze-fixation and freeze-substitution preserved the
      antigenicity of the fibrillar collagens organized in a compact three-dimensional
      network, whereas immunolabeling failed after conventional electron microscopic
      procedures. These cryostabilization techniques appear to be of value to improve
      the immunolocalization of collagens.

PMID- 9010477
TI  - Thymic overexpression of CD40 ligand disrupts normal thymic epithelial
      organization.
AB  - We characterized the distribution of CD40 and CD40 ligand (CD40-L) in the adult
      and developing murine thymus. Before birth, CD40 was almost exclusively localized
      to scattered foci of medullary cells. By birth there was a dramatic upregulation
      of CD40 expression by cortical epithelial cells, which was accompanied by a
      consolidation of medullary epithelial foci. CD40-L+ thymocytes displayed a
      medullary location. Analysis of mice deficient in CD40-L expression indicated
      that CD40-L/CD40 interactions were not required for development of the medullary
      compartment. Overexpression of CD40-L targeted to thymocytes altered thymic
      architecture, as reflected by a dramatic loss of cortical epithelial cells,
      expansion of the medullary compartment, and extensive infiltration of the capsule
      with a mixture of CD3+ cells, B-cells, and macrophages/dendritic cells.
      Reconstitution of lethally irradiated normal mice with lck CD40-L bone marrow
      cells also resulted in loss of cortical epithelium and expansion of the medullary
      compartment. Disruption of the normal pattern of thymic architecture and
      epithelial differentiation as a consequence of increased intrathymic levels of
      CD40-L expression points to a role for CD40-L/CD40 interactions in the normal
      pattern of epithelial compartmentalization/differentiation within the thymic
      environment.

PMID- 9010478
TI  - How to examine the antigen-damaging effect of sodium ethoxide on deplasticized
      epoxy sections.
AB  - The purpose of this investigation was to develop a method that could be used to
      estimate how damaging sodium ethoxide is to different antigens with respect to
      immunolabeling when epoxy sections are deplasticized. If we obtain weak labeling
      for an antigen on deplasticized epoxy sections, this might be caused by the
      damaging effect of the ethoxide solution. It is therefore interesting to develop
      a method to check if this really is the reason. Fibrin clots and tissues of human
      kidney and thyroid were embedded in LR White resin. Some thin sections from these
      specimen blocks were exposed to sodium ethoxide in the same way as epoxy sections
      are when being deplasticized. Other sections from the same blocks were not
      exposed to sodium ethoxide. Both categories of sections were immunogold-labeled
      with anti-fibrinogen, anti-thyroglobulin, anti-IgA, anti-IgG, or anti-IgM. The
      intensity of immunolabeling of sections treated with ethoxide was compared with
      the immunolabeling of corresponding sections that were not treated with ethoxide.
      No significant differences were found in immunolabeling for fibrinogen, IgA, IgG,
      and IgM. For thyroglobulin, the intensity was approximately 30% less in tissues
      that were exposed to sodium ethoxide. The practical significance of this method
      is that we easily can examine the degree to which a given antigen is affected by
      sodium ethoxide, which is the agent used for deplasticizing epoxy sections.

PMID- 9010479
TI  - Adenosine and neuronal plasticity.
AB  - Adenosine is considered an important neuromodulator of the nervous system acting
      at pre-, post- and non-synaptic levels. In the present review we describe how
      adenosine modifies paired-pulse facilitation (PPF), posttetanic depression (PTD),
      long-term potentiation (LTP), long-term depression (LTD) and depotentiation at
      the hippocampus, and therefore how this nucleoside modulates synaptic plasticity.

PMID- 9010480
TI  - Ethanol-induced emesis in the house musk shrew, Suncus murinus.
AB  - Ethanol-induced emesis were investigated using Suncus murinus and the emetogenic
      mechanisms of ethanol were compared with those of cisplatin. Intraperitoneal
      injection of ethanol caused dose-dependent emesis with ED50 value of 22.3% (v/v)
      when injection volume was adjusted to 4 ml/kg. Intraperitoneal and subcutaneous
      injection of acetaldehyde also caused dose-dependent emesis (ED50 = 3.5% (v/v)
      with an extremely shorter latency (6% i.p.: 1.0 +/- 0.3 min cf. 40% ethanol: 13.0
      +/- 1.9 min). Neither ethanol nor acetaldehyde caused emetic responses when
      injected intracerebroventricularly. Pretreatment with disulfiram, an inhibitor of
      liver aldehyde dehydrogenase, potentiated the emetogenic effects of ethanol.
      Surgical abdominal vagotomy, which blocks cisplatin-induced emesis completely,
      did not prevent ethanol-induced emesis. 5-HT3 receptor antagonists, which also
      cause complete inhibition of cisplatin-induced emesis, did not affect the
      responses. However, ethanol-induced emesis was prevented by the pretreatment with
      8-hydroxy-2-(di-n-propylamino)tetrarin hydrobromide (8-OH-DPAT) and N-(2
      mercaptopropionyl)-glycine (MPG) dose-dependently. The tackykinin NK1 receptor
      antagonist (+)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl-piperidine (CP-99,994)
      also attenuated ethanol-induced emesis. Taken together, these results suggest
      that 1) acetaldehyde is probably responsible for ethanol-induced emesis, 2)
      active site for ethanol maybe peripheral, 3) ethanol-induced emesis is mediated
      by free radicals, and 4) mechanism of ethanol-induced emesis and that caused by
      cisplatin are different in many respects, although in some they are similar and
      that the precise pathways remain to be identified. Therefore, the tolerance to
      emetogenic effects of cisplatin in alcoholic patients cannot be explained as a
      simple cross desensitization of the pathway.

PMID- 9010481
TI  - Effect of potassium channel modulators on male sexual behavior.
AB  - In the adult sexually experienced male rat, the intracerebroventricular (i.c.v.)
      injection of pinacidil, a KATP channel opener, at the dose of 100-150-300
      micrograms/rat worsened the copulatory performance in the presence of a receptive
      female, whereas the administration of glibenclamide, a KATP channel blocker, at
      the dose of 0.5 and 3 mg/kg intraperitoneally (i.p.) had an improving effect.
      These data indicate that KATP channels in target neurons may play an important
      role in the physiology of male sexual behavior.

PMID- 9010482
TI  - Neuropeptides in the saliva of healthy subjects.
AB  - Five neuropeptides: Substance P (SP), Neurokinin A (NKA), Calcitonin Gene-Related
      Peptide (CGRP), Neuropeptide Y (NPY) and Vasoactive Intestinal Polypeptide (VIP),
      were measured in the saliva of eight subjects. The saliva was collected using
      different stimulation techniques: whole resting saliva, whole paraffin stimulated
      saliva, whole citric acid stimulated saliva and parotid saliva of different
      secretion rates -0.25 mL/min, 0.50 mL/min and 1.00 mL/min, also stimulated by
      citric acid. The neuropeptides were analysed by radioimmunoassay. The results
      showed that the concentration of all neuropeptides decreased significantly, two-
      to four-fold (CGRP up to 16-fold) in whole saliva, when the salivary secretion
      rates increased six- to eight-fold due to stimulation. However, the amounts of
      all neuropeptides released over time into the whole saliva increased two- to five
      fold (ten-fold for CGRP) as the volumes of saliva increased due to chewing
      stimulation as compared to resting saliva or citric acid stimulated saliva. There
      was also more CGRP in the resting saliva than in the citric acid stimulated
      saliva. The concentration of CGRP in the parotid saliva decreased three- to ten
      fold when the salivary flow increased, whereas the concentration of NKA increased
      three- to four-fold and that of NPY almost two-fold under the same conditions.
      The concentrations of SP and VIP did not change in the different flows of parotid
      saliva. The release of all neuropeptides in the parotid saliva over time showed
      significant increases (3-14-fold) when the secretion rates increased except CGRP,
      which showed no changes at all. We concluded that neuropeptides are continuously
      released into the saliva. Their amounts increase with stimulation, but they are
      diluted by the increased volume of saliva, and they are also affected by the mode
      of stimulation-muscular activity leads to a greater release than citric acid
      stimulation. As the neuropeptides play an important role in the control of
      salivary secretory mechanisms, their normal occurrence and release are of
      fundamental importance for the understanding of the function of the salivary
      glands.

PMID- 9010483
TI  - Urinary pyrraline as a biochemical marker of non-oxidative Maillard reactions in
      vivo.
AB  - The presence of pyrraline, a non-oxidative glucose-derived Maillard reaction
      product in plasma proteins has been established previously. In this study we have
      investigated the presence of pyrraline in human urine to determine whether
      pyrraline-containing proteins are metabolized or selectively retained. Pyrraline
      was detected by means of HPLC, and its presence was confirmed by UV and
      electrospray-mass spectrometry. The quantification of pyrraline in urine from
      healthy individuals showed 1.21 +/- 0.4 micrograms/mg creatinine. In urine from
      diabetic patients, pyrraline levels varied considerably, although the mean level
      was higher than in healthy subjects (1.37 +/- 0.6 micrograms/mg creatinine).
      These data further support the presence of a catabolic pathway for advanced non
      oxidative Maillard reaction products in vivo and suggest their role in the
      pathogenesis of diabetes.

PMID- 9010484
TI  - Circadian rhythms of plasma atriopeptin, plasma renin activity and plasma
      aldosterone in patients with hepatorenal syndrome.
AB  - The etiology of hepatorenal syndrome (HRS) is still incompletely understood, but
      the atriopeptin-renin-aldosterone system plays an important role in its
      pathogenesis. Since this system presents a circadian rhythmicity, the aim of the
      study was to investigate the circadian rhythm in the circulating concentrations
      of atriopeptin (atrial natriuretic peptide, pANP), plasma renin activity (PRA)
      and plasma aldosterone (pA) in patients with HRS, compared with healthy controls.
      Venous blood samples were drawn during the span of a whole day and every two
      hours from a peripheral vein in 10 healthy subjects and in 10 patients with HRS.
      The circulating concentrations of pANP, PRA and pA were determined by
      radioimmunoassay. Statistical analysis was carried out by the "cosinor" method.
      The controls presented a significant (p < 0.05) circadian rhythm for each
      variable, whereas no rhythm (p > 0.05) was found in HRS patients. The pANP, PRA
      and pA rhythms were significantly (p < 0.05) different between the two groups,
      HRS patients having higher mean daily concentrations and larger circadian
      variations of pANP, PRA and pA than controls. Significant relations (p < 0.05)
      were demonstrated between the mean daily concentrations of pANP and PRA (r =
      0.79), PRA and pA (r = 0.73) and PRA and pA (r = 0.76) in the controls; on the
      contrary, the HRS patients showed only a significant (p < 0.05) positive relation
      between pANP and PRA (r = 0.71). These results confirm the previous observation
      that the atriopeptin-renin- aldosterone system presents a well-defined circadian
      time structure in healthy subjects, while the HRS patients present a complete
      loss of the secretory sequentiality and of the circadian rhythm, with
      desynchronization of the whole system. This great upset in the temporal and
      functional organizations of the system could play an important role in promoting
      and/or in maintaining the hydro-electrolyte unbalance of HRS.

PMID- 9010485
TI  - Prevalence of diabetes and factors associated with diabetic complications in
      Oneida Indians.
AB  - The study objective was to determine the prevalence of diabetes mellitus among
      Oneida Indians and to identify factors associated with the development of medical
      complications. After identifying patients with diabetes (N = 373) treated at the
      Oneida Community Health Center, their medical records were reviewed to determine
      age, body mass index (BMI), types of medication used, HbAlc, and the presence of
      diabetic complications. The age and sex-adjusted prevalence of diabetes was
      86.5/1000 population. Where type of diabetes could be determined (N = 345) 96%
      were non-insulin dependent; 67% were afflicted with diabetic complications. 56%
      had hypertension. Age, BMI, and HbAlc were significant variables with respect to
      the presence of certain complications. Although lower than the prevalence for
      some other groups of Native Americans, diabetes and its complications represent a
      serious problem for the Oneida Indians. Consistent screening, intensive
      intervention and culture-sensitive prevention efforts focussing on weight control
      are needed.

PMID- 9010486
TI  - Calcein is excreted from the intestinal mucosal cell membrane by the active
      transport system.
AB  - In this study, we report the efflux mechanism of calcein, an organic anion,
      mediated by a multidrug resistance-associated protein (MRP)-like protein in the
      intestinal mucosal membrane. The transport of calcein from the mucosal to serosal
      side was decreased dose-dependently and was significantly lower than that of the
      opposite direction. In addition, its transport was increased in the presence of
      metabolic inhibitors and probenecid. Furthermore, the efflux of calcein from the
      intestinal cell membrane, which was preloaded with calcein acetoxymethyl ester,
      was predominantly observed in the mucosal side rather than in the serosal side.
      Its efflux to the mucosal side was inhibited by the metabolic inhibitors and
      probenecid, not by verapamil which is a P-glycoprotein substrate. These results
      indicated that the transport of calcein and possibly other organic anions across
      the intestinal membrane may be regulated by the MRP-like protein, but not P
      glycoprotein.

PMID- 9010487
TI  - Characterization of beta-adrenergic receptors of freshly isolated astrocytes and
      neurons from rat brain.
AB  - The binding and characteristics of rat brain beta-adrenergic receptors (beta-AR)
      isolated from astrocytes and neurons were investigated. Equilibrium binding
      experiments demonstrated that beta-AR were more concentrated on astrocytes than
      on neurons isolated from forebrain, cerebral cortex and cerebellum. Inhibition
      experiments revealed that beta 1-AR and beta 2-AR were present in the two cell
      types. Isoproterenol revealed two interchangeable states of high and low affinity
      binding to both beta 1- and beta 2-AR in neurons. The high affinity binding sites
      were sensitive to guanylylimidodiphosphate (GppNHp). Similar results were found
      with other beta-AR agonists but not with salbutamol and salmeterol which
      recognized both affinity states of the neuronal beta 2-AR but only the low
      affinity state of beta 1-AR. In astrocytes only the low affinity state of beta-AR
      was observed.

PMID- 9010488
TI  - Inhibitory effect of di-catechol rooperol on VCAM-1 and iNOS expression in
      cytokine-stimulated endothelium.
AB  - Induced expression of vascular cell adhesion molecule-1 (VCAM-1) and of nitric
      oxide synthase (iNOS) is believed to play a role in the pathogenesis of
      atherosclerosis, asthma, as well as other inflammatory disorders. In the current
      study we examined the effect of the di-catechol rooperol [(E)-1,5-bis (3',4'
      dihydroxyphenyl) pent-4-en-1-yne] on the process of microvascular endothelial
      cell (MME) activation by TNF-alpha and IFN-gamma. We show that rooperol decreases
      VCAM-1 and iNOS mRNA levels in cytokine-activated MME with subsequent inhibition
      of VCAM-1 membrane expression as measured by adhesion of P815 cells to MME
      monolayers, and NO production, as reflected in the nitrite concentration in
      culture medium. The properties of rooperol now described suggest that rooperol
      may be an anti-inflammatory agent useful in the treatment of several inflammatory
      disorders.

PMID- 9010489
TI  - Decreased total antioxidant capacity but normal lipid hydroperoxide
      concentrations in sera of critically ill patients.
AB  - Oxidative stress (when free radical generation exceeds antioxidant defense)
      occurs in many human diseases and makes significant contributions to their
      pathogenesis. We automated assays estimating the antioxidant status of serum, and
      lipid hydroperoxide concentrations using the Monarch analyzer. In this assay, the
      antioxidant status of serum is measured by its ability to inhibit generation of
      free radicals from 2,2'-amino-di-[3-ethylbenzthiazole sulphonate] by metmyoglobin
      and hydrogen peroxide. The assay for measuring lipid peroxidation products in
      serum utilizes the ability of lipid hydroperoxides to generate methylene blue
      from 10N-methylcarbamyl 3,7-dimethylamino 10H-phenothiazine. We detected no lipid
      hydroperoxide in sera obtained from 24 controls. The mean antioxidant status was
      1.69 mmol/l (SD; 0.20 mmol/l) in controls. The antioxidant capacity of serum was
      significantly reduced in sera of critically ill patients in the medical intensive
      care unit (mean = 1.05, SD = 0.26 mmol/l) with p value less than 0.05 by
      independent t-test, two tailed. Lipid peroxidation products were not
      significantly elevated in critically ill patients, however lipid peroxidation
      products were significantly elevated in hemodialysis patients (mean = 1.40, SD =
      0.47 mumol/l) and in some kidney transplant recipients. We conclude that
      antioxidant capacity of sera in critically ill patients is significantly reduced.

PMID- 9010490
TI  - Pharmacological characterization of a vasopressin V1 receptor in the isolated
      human gastric artery.
AB  - Species-related specific differences in the pharmacological profile of
      vasopressin V1a receptors have been reported. Thus, the aim of the present study
      was to identify a vascular preparation of human origin expressing V1a receptors.
      Vasopressin was found to contract human gastric artery strips without endothelium
      with high affinity (pEC50 8.9). The maximal effect induced by vasopressin was
      inversely related to the diameter of the vessel. Oxytocin was found to contract
      the human gastric artery strips with low potency (pEC50 7.2). Contraction induced
      by vasopressin was competitively antagonized by the non peptide vasopressin
      receptor antagonists SR 49059 (pA2 9.2), OPC 21268 (pA2 6.2) and OPC 31260 (pA2
      7.1). The order of potency of agonists (vasopressin > > oxytocin) and of
      antagonists (SR 49059 > > OPC 31260 > OPC 21268) indicate the contraction induced
      by vasopressin in the isolated human gastric artery is mediated by the V1a
      receptor type. The present data are similar to those obtained in different
      preparations expressing the native human V1a receptor as well as to those
      obtained in cell transfected with this receptor. The human gastric artery is a
      monoreceptor system of great utility for studying the effects of new drugs
      interacting with the human V1a receptor.

PMID- 9010491
TI  - Effect of haloperidol on the development of the solid Ehrlich tumor in mice.
AB  - We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol (s.c)
      on the development of the Ehrlich solid carcinoma, after inoculation of 1.5 x
      10(6) Ehrlich ascites tumor cells into the left footpad of mice. The footpad
      thickness of haloperidol treated animals was significantly smaller than control
      from day two after tumor inoculation, to the end of the experiment.
      Histopathological examination showed that haloperidol treated mice apparently
      presented less necrotic areas within the tumor mass as well as less invasion of
      subepithelial connective tissue and other adjacent structures. In particular, in
      comparison with the control group, no nerve bundles were invaded by neoplastic
      cells in experimental mice. The possible mechanism underlying these results is
      discussed in light of the specific pharmacological properties of this
      neuroleptics drug.

PMID- 9010492
TI  - A new antithrombotic agent, aspalatone, attenuated cardiotoxicity induced by
      doxorubicin in the mouse; possible involvement of antioxidant mechanism.
AB  - A new antithrombotic agent, aspalatone (APT; acetyl salicylic acid maltol ester),
      was synthesized by esterification of acetyl salicylic acid (ASP) and maltol
      (MAL). It was suggested that APT possessed an antioxidant effect in in vitro. To
      evaluate the putative antioxidant effect of APT in in vivo, we developed
      doxorubicin (DOX)-related cardiac damage, which might be implicated by oxidative
      stress. Vitamin E (Vit E) was included in the present study as an example of an
      antioxidant. Prolonged treatments with APT, MAL and Vit E significantly reduced
      the mortality in animals receiving multiple dose of DOX (3 mg/kg x 4). The
      potential role of APT, MAL and Vit E against DOX insult may be explained by the
      induction of glutathione peroxidase activity accompanied by the inhibition of
      lipid peroxidation. Prolonged treatments of APT, MAL and Vit E also ablated
      histopathological evidence of DOX cardiomyopathy. ASP challenge, however, did not
      affect the mortality, myocardial lesion and antioxidant deficit induced by DOX
      treatments. In conclusion, the protective effect of APT was equipotent to that of
      Vit E against DOX cardiotoxicity. The results also suggest that the
      antiperoxidative effect of APT plays a protective role in DOX-related cardiotoxic
      side effect.

PMID- 9010493
TI  - Smoking and immunity: an additional player in the mosaic of autoimmunity.
AB  - Autoimmune diseases are associated with a variety of predisposing factors.
      However, the relative contribution of each remains to be established. The purpose
      of the paper is to focus on cigarette smoking, a common Western habit, as a
      possible environmental factor for the emergence of autoimmunity. This association
      is described in view of several recent studies documenting increased
      susceptibility to autoimmune diseases among smokers.

PMID- 9010494
TI  - Characterization of the 5' flanking region of the human complement factor H gene.
AB  - The promoter region of the human factor H gene was cloned and a 3 kb Eco RI
      fragment was sequenced. Primer extension and S1 nuclease analysis were used to
      determine the transcription start site, which was found to be 10-11 nucleotides
      upstream of the published cDNA sequence. No canonical TATA or CCAAT boxes were
      found in conjunction with this site. The sequence from the human H promoter
      region was compared to that from the mouse gene. There was a region of 800 bp
      that was 62.5% identical between the two sequences. The sequences of the two
      promoter regions were compared to a database of transcription factor binding
      sites. Five elements were identified that matched the consensus sequence 100% and
      were identical in the two promoter sequences. Promoter assays using the
      luciferase reporter gene demonstrated that this region contained a functional
      transcription start site and putative enhancer elements. U118-MG astroglioma
      cells and Hep3b hepatoma cells were incubated with various cytokines to measure
      effects on their factor H mRNA levels. Interferon-gamma (IFN-gamma), but not
      interleukin-1 (IL-1), tumour necrosis factor alpha (TNF-alpha) or IL-6, was able
      to increase the level of H mRNA in both cell lines.

PMID- 9010495
TI  - Immunological induction of flavour aversion in mice. II. Passive/adoptive
      transfer and pharmacological inhibition.
AB  - Mice immunized with ovalbumin develop a strong aversion to ingesting sweetened
      egg white dilutions or ovalbumin solutions. In immunized animals, gavage or
      voluntary ingestion of ovalbumin triggers an increase of vascular permeability in
      the intestine; pretreatment with a mixture of histamine and serotonin antagonists
      blocked this reaction, but not the aversion; dexamethasone inhibited both the
      aversion and the increase in permeability. The aversion was transferred to normal
      recipient mice with high-titre anti-Ova sera obtained with complete Freund's
      adjuvant, but not with lower-titre serum pools of mice immunized with the help of
      Al(OH)3 adjuvant. However, the aversion was also (adoptively) transferred with
      whole spleen cells from immune donors. This later condition is inefficient to
      transfer the formation of high titres of specific antibodies.

PMID- 9010496
TI  - Inhibition of neutrophil apoptosis by antioxidants in culture medium.
AB  - Neutrophil apoptosis is an important mechanism that has implications for
      understanding the life span and toxic potentials of neutrophils at inflamed
      sights. In this study the authors examined the possibility that reactive oxygen
      species (ROS) released by neutrophils can regulate neutrophil survival. Cu,Zn
      superoxide dismutase (Cu,Zn-SOD), Mn-SOD, and catalase in culture media were
      significantly effective in delaying the spontaneous apoptosis, suggesting that
      ROS play an important role in the resolution of inflammation by inducing
      neutrophil apoptosis. In this experiment, boiled Cu,Zn-SOD had no effect on
      inhibiting the apoptosis, but boiled Mn-SOD from Bacillus stearothermophilus was
      more effective in inhibiting the apoptosis than untreated Mn-SOD at the same
      dose. However, the boiled Mn-SOD showed only 80% of O2- inhibitable activity
      compared with the untreated Mn-SOD. This effect may be attributed to the partial
      liberation of manganese because MnCl2 inhibited the apoptosis effectively.
      Furthermore, Cu,Zn-SOD was effective in delaying apoptosis only when added to the
      culture within the first 3 h of incubation, suggesting that the isolation of
      neutrophils from peripheral blood enhances apoptosis of neutrophils.

PMID- 9010497
TI  - The susceptibility to cytotoxic T lymphocyte mediated lysis of chemically induced
      sarcomas from immunodeficient and normal mice.
AB  - A panel of sarcomas induced with 3-methylcholanthrene in normal and
      immunodeficient mice was studied for their capacity to present antigen by the
      endogenous, MHC class I restricted pathway. Lymphocytic choriomeningitis virus
      was used to infect cultured tumour cells, and the infected cells were tested for
      susceptibility to cytolysis by virus specific cytotoxic T cells. Tumour cells
      originating from tumours induced in immunocompetent C.B.-17 mice presented virus
      antigen more efficiently than tumour cells from immunodeficient SCID mice. No
      significant difference in virus antigen presentation was found between tumours
      from nude and nu/+ BALB/c mice. The sensitivity of target cells from the
      individual tumours to cytotoxic T lymphocyte (CTL) mediated lysis correlated
      negatively with their sensitivity to natural killer (NK) cell mediated lysis.
      There was a positive correlation between the sensitivity to CTL mediated lysis
      and surface expression of the MHC class I molecule Ld of the tumour cells. Tumour
      cells incapable of in vitro presentation of viral antigen to specific cytotoxic T
      cells originated from tumours known from previous experiments to be readily
      accepted after transplantation to immunocompetent, histocompatible recipients.

PMID- 9010498
TI  - An endogenous superantigen in the rat gut lumen as a model to study the role of
      human protein-Fv.
AB  - Protein-Fv (pFv) is a human B superantigen which can bind the variable domain
      (VH) of the heavy chain of immunoglobulins (Igs) and enhance the effector
      functions of secretory antibodies in the gut lumen. This study describes a rat
      molecule related to pFv by a similar specificity to the human VH3 domain.
      Investigation of the content of different gut segments shows that the rat pFv is
      usually hidden by its binding to local Igs to form macromolecular complexes
      similar to the immune fortresses described in normal humans. Furthermore, the pFv
      level generally increases from the jejunum to the colon in parallel with the
      decreasing water dilution, and finally a discontinuous presence can occur along
      the digestive tract. Detection of this molecule in the fetus proves its non
      microbial origin. Variations of the release of pFv, according to the breeding and
      to littermating, suggest the influence of external factors. This animal model
      allows the development of a study of the functions of pFv in vivo using a current
      laboratory species and has already provided evidence that the synthesis of this
      important molecule of the secretory immune system is regulated by environmental
      factors.

PMID- 9010499
TI  - IgG2b inducing factor from rheumatoid arthritis synovial fluid activates antibody
      production in highly purified mouse B lymphocytes.
AB  - Rheumatoid arthritis synovial fluid (RA-SF) contains a factor that induces IgG2b
      antibody production in LPS-stimulated murine B cells and therefore is called
      IgG2b inducing factor (IgG2bIF). When LPS, together with crude RA-SF or semi
      purified IgG2bIF, was added to highly purified LPS-stimulated B cells, the number
      of IgG2b-producing cells was substantially enhanced. This shows that IgG2bIF acts
      directly on activated B cells, presumably by binding to a receptor expressed on
      LPS-activated B cells. In vivo LPS-activated B blasts were not able to respond to
      RA-SF unless LPS was present in vitro, showing that LPS is needed to maintain
      cell viability and responsiveness to the IgG2bIF. To elucidate the mechanism for
      the IgG2bIF effect on highly purified B cells, the IgG2b response of LPS
      stimulated, Bruton's tyrosine kinase-defective, xidB blasts was studied. Purified
      B blasts from the btk-defective CBA/N mouse strain were sensitive to IgG2bIF.
      These findings show that IgG2bIF acts directly on B cells and activates cells
      through a btk-independent pathway.

PMID- 9010500
TI  - IgG2b inducing factor from rheumatoid arthritis synovial fluid synergizes with
      transforming growth factor-beta in promoting IgG2b antibody production in mouse B
      lymphocytes.
AB  - Rheumatoid arthritis synovial fluid (RA-SF) contains a distinct biological
      activity that selectively induces IgG2b production in LPS-activated murine B
      blasts. This IgG2b inducing factor (IgG2bIF) acts directly on purified LPS
      activated B blasts from normal and Bruton's tyrosine kinase-defective CBA/N mice.
      In order to test the possibility that TGF-beta and IgG2bIF in RA-SF act in
      concert to induce IgG2b production, anti-TGF-beta monoclonal antibodies and RA-SF
      were added to LPS-activated CBA B blasts, which led to a marked reduction of
      IgG2b-producing cells. This result indicates that TGF-beta and IgG2bIF in RA-SF
      synergize in the induction of IgG2b production. TGF-beta antibodies do not
      inhibit IgG2b production in CBA/N B blasts, further substantiating our earlier
      notion that CBA/N B blasts have a higher endogenous production of TGF-beta after
      LPS stimulation, which might be responsible for the aberrant reactivity in btk
      deficient CBA/N mice. RA-SF is able to reconstitute the deficient IgG1 response
      in LPS- and IL-4-stimulated CBA/N B blasts. Addition of antibodies against TGF
      beta had only a marginal effect on the IgG1 response, indicating that the
      reconstitution is mediated by another factor(s), which is present in RA-SF.

PMID- 9010502
TI  - Selective usage of VH genes in adult human B lymphocyte repertoires.
AB  - The authors have compared the VH gene utilization patterns among small resting
      immunocompetent B cells and large naturally activated B lymphocytes of healthy
      human adults. They employed a non-radioactive RNA in situ hybridization technique
      that allows detection of VH gene family expression at the single cell level.
      Pokeweed mitogen stimulated and unmanipulated mononuclear cells from peripheral
      blood and spleen of unrelated individuals were hybridized to digoxigenin-labelled
      antisense RNA probes specific for human VH families 1-6 and for the constant
      region genes C mu and C gamma. The observed VH gene family utilization patterns
      did not correlate with the genomic complexity of human VH genes. The VH3 gene
      family was most frequently used among resting B cells in both peripheral blood
      and spleen. Among naturally activated lymphocytes the VH6 gene was markedly over
      represented, while expression of the VH1 and VH3 gene families was decreased. The
      data show that V-region mediated selection participates in shaping the peripheral
      antibody repertoire in healthy adults.

PMID- 9010501
TI  - Detection of alterations in the levels of neuropeptides and salivary gland
      responses in the non-obese diabetic mouse model for autoimmune sialoadenitis.
AB  - The salivary glands of non-obese diabetic (NOD) mice and BALB/c controls were
      evaluated for the stimulatory effects of the following neuropeptides; substance P
      (SP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY).
      Injection of either of the three neuropeptides in combination with the muscarinic
      cholinergic agonist pilocarpine increased saliva flow rates in BALB/c mice while
      there was no observable augmentation to flow rates in pre-diabetic or diabetic
      NOD mice. Small increases in protein content of the stimulated saliva were
      observed in the BALB/c group of animals with the injection of any of the above
      neuropeptides in combination with pilocarpine. In pre-diabetic NOD animals, only
      VIP and NPY increased the protein content-ratio above pilocarpine alone.
      Radioimmunoassay determination of neuropeptide concentrations in the
      submandibular and parotid glands revealed reduced levels of SP with diabetes
      onset as compared with pre-diabetic NOD or BALB/c mice. The levels of NPY were
      similar between BALB/c and NOD animals except in the pre-diabetic parotid gland
      where NPY concentrations were 1.3-fold greater. On the other hand, VIP
      concentrations were substantially reduced in the submandibular gland of NOD mice,
      while in the parotid gland neuropeptide levels were evaluated 3.8-fold relative
      to BALB/c controls. Immunohistochemical staining of the parotid and submandibular
      glands for SP revealed primarily ductal cell staining which was reduced with
      diabetes onset in NOD animals. These findings further define the sialoadenitis
      observed in NOD mice to be due, in part, to a general loss of neurotransmitter
      responsiveness on the part of salivary gland cells.

PMID- 9010503
TI  - Cytokine mRNA profile of peripheral blood mononuclear cells isolated from
      individuals with Trypanosoma cruzi chronic infection.
AB  - Characterization of immunologic activities during chronic infection with
      Trypanosoma cruzi is critical for understanding the dynamics of human Chagas'
      disease. Since cytokine production is mainly regulated by transcription and mRNA
      stability, quantitative RT-PCR analysis gives an accurate picture of the
      influences of disease on cytokine profile. Using RT-PCR, the authors analysed the
      levels of message expression for several cytokines in peripheral blood
      mononuclear cells (PBMC) freshly isolated from chagasic patients (CP) and non
      infected individuals (NI), and in in vitro-stimulated PBMC from CP. Ex vivo
      analysis showed that mean levels of expression of IL-5, IL-10, IL-13 and IFN
      gamma were dramatically increased in PBMC from CP, compared to NI. The levels of
      IL-2 and IL-4 were not significantly different between groups. Analysis of
      cytokine mRNA production after in vitro culture with parasite-derived antigens
      (EPI or TRP) or anti-epimastigote antibodies (Id) showed that these two classes
      of stimuli induced distinct cytokine responses. While EPI or TRP induced higher
      production of IFN gamma specific message and low IL-10, anti-Id cells produced
      higher levels of IL-10 and low IFN gamma. The simultaneous presence of antigenic
      and antibody stimulation in the host during the chronic phase of Chagas' disease
      could explain the existence of both inflammatory and anti-inflammatory cellular
      reactivity detected in most patients.

PMID- 9010504
TI  - HIV antigens and T-cell receptor variable beta chain families.
AB  - The authors investigated whether the human immunodeficiency virus (HIV) has
      restrictive effects on the variable region of the beta chain (V beta) of the T
      cell antigen receptor (TCR), by in vitro cultivation of non-HIV-infected
      peripheral blood lymphocytes with one of six HIV antigens or heat-inactivated
      whole virus (HIV-HI). Resting and blastic CD4+ and CD8- cells were assessed with
      3-colour cytofluorometry and monoclonal antibodies to various V beta
      families/subfamilies. The V beta families affected include V beta's 13.1/.3, 8,
      and 21 with gp 120; V beta 21 with gp 160 and RT; V beta 8 with p25; V beta's 8
      and 21 with Rev; and V beta's 3 and 21 with HIV-2 Vpx. V beta family-specific
      effects with HIV-HI did not differ significantly from those found with IL-2
      stimulation. Findings differed between CD4+ and CD8+ cells. For CD4+ lymphocytes,
      significant V beta-specific decreases were found, not the expansions found with
      superantigens or mitogens. CD8+ lymphocytes showed slight but significant
      expansions. The effects on V beta's 8, 13, and 21 are consistent with previous
      studies of HIV-infected persons. However, it is difficult to accept that antigens
      encoded by different HIV genetic regions cause proportionate diminutions of
      similar V beta families. The authors suggest that these effects may be secondary
      to changes in cytokine profiles rather than direct interactions with TCR V
      beta's.

PMID- 9010505
TI  - Lymphokine-activated cytotoxicity in peripheral blood mononuclear cells of
      severely immunocompromised HIV-infected patients.
AB  - The authors determined the natural killer (NK) and lymphokine-activated killer
      (LAK) activities of peripheral blood mononuclear cells (PBMCs) from a severely
      immunocompromised (CD4 cell counts < 100/mm3) group of AIDS patients, using K562
      and U937 target cells. An increase in cytotoxicity was observed in the PBMCs of
      all 17 patients following a 48 h incubation with the combination of 400 U/ml of
      recombinant gamma interferon plus 20 U/ml of natural interleukin-2. Although NK
      and LAK activities were significantly higher in healthy controls than in
      patients, patients' LAK activity was higher than the NK activity of controls. The
      authors also demonstrated that the use of medium containing fetal bovine serum,
      when compared with medium containing autologous serum, increases NK activity
      without affecting LAK activity. Lymphokine augmentation of cytotoxicity is
      achievable in severely immunocompromised AIDS patients and might be of benefit in
      delaying opportunistic infections and malignancies.

PMID- 9010506
TI  - Induction of apoptosis and cytokine gene expression in T-cell lines by sera of
      patients with systemic lupus erythematosus.
AB  - Accelerated apoptosis and improper expression of cytokine genes have been
      considered as important defects of lymphocytes for the development of systemic
      lupus erythematosus (SLE). This study was undertaken to test the possible
      contribution of serum factors obtained from SLE patients to these abnormalities.
      Molt-4 and Jurkat cells constantly exhibited a slower growth rate as well as more
      dead cells in culture with SLE sera tested than controls, although the cell cycle
      progression was apparently unaffected. Increased apoptosis was demonstrable among
      SLE sera-cultured cells by ELISA for apoptosis-specific DNA fragments and
      terminal deoxynucleotidyl transferase (TdT) in situ death analysis. Different
      levels of Fas, Fas-L, and Bcl-2 gene products were not detected between SLE sera
      treated cells and the controls. The transcripts of interleukin-10 (IL-10) and
      interferon-gamma (IFN-gamma) genes of these two T cell lines were evidently
      increased in the presence of SLE sera, while IL-2 and IL-4 were unaffected.
      Elevated expression of IL-5 was also found in Molt-4 cells. By contrast, SLE sera
      reduced the transcripts of IL-6 gene in Jurkat cells. The effects of SLE sera
      were independent of corticosteroid medication. These results suggest that serum
      abnormalities may also play a role in T cell dysfunction.

PMID- 9010507
TI  - Predominance of detrimental humoral immune responses to HIV-1 in AIDS patients
      with CD4 lymphocyte counts less than 400/mm3.
AB  - The humoral immune response to human immunodeficiency virus type 1 (HIV-1) was
      studied in 25 AIDS patients with CD4 lymphocyte counts of less than 400/mm3.
      Humoral immune responses against tissue culture adapted strains of HIV-1, and two
      limited-passage patient isolates were investigated. Total anti-HIV antibody
      levels were not significantly different between different individuals.
      Neutralizing titres against HIVLA1 and HIVSF2 were 10- to 100-fold higher than
      against clinical isolates. The complement-mediated, antibody-dependent
      enhancement of HIV-1 infection titre was high (mean 1:14,000). Antibody
      complement mediated cytotoxicity of both HIVLA1 and HIVSF2 was ineffective using
      human complement as a complement source. The antibody-dependent, cell-mediated
      cytotoxicity (ADCC) activity varied against the four isolates with tissue culture
      adapted strains being more susceptible than clinical isolates. Finally, an ADCC
      effector cell function, natural killer or NK activity, was measured for all 25
      patients, and NK activity of patients was decreased by nearly 75% compared to
      uninfected individuals. In summary, beneficial humoral immune responses are low
      in HIV-1 infected individuals with CD4 counts of less than 400/mm3 if the in
      vitro assay system is constructed to best mimic the in vivo situation. These
      results suggest that the lack of functional antibody responses to HIV may play an
      important role in viral pathogenesis.

PMID- 9010508
TI  - The transition from underground to legal syringe exchange: the New York City
      experience.
AB  - The most common method of syringe exchange program (SEP) development in the
      United States has been for SEPs to be started by activists without funding and
      then to become a government-funded community-based organization. This
      developmental process, which has not been studied to date, involves major
      organizational change. We report our findings on three New York City syringe
      exchanges experiencing this type of transition. Our data illustrate that
      following legalization, increased legitimacy and funding allowed all three SEPs
      to expand the size and scope of their programs (e.g., adding hours, sites,
      referral services, and the ability to support user groups), resulting in a rapid
      growth in participation (over 15,000 in 18 months). Regulation accompanying
      legalization posed significant challenges to SEPs, including added record-keeping
      and reporting tasks, increased demand for referrals, and accommodating
      evaluation, which affected already overburdened staffs. The transition process
      poses significant challenges to these developing organizations as well as
      opportunities for improved services.

PMID- 9010509
TI  - Multiple sexual partners and condom use among long-distance truck drivers in
      Thailand.
AB  - Sexual behaviors of long-distance truck drivers in Thailand were investigated to
      define patterns and determinants critical to the transmission of HIV. This
      article reports on commercial, spousal, and other sexual partners and on condom
      use among 327 drivers interviewed in 1992. Forty-eight percent reported a
      commercial sex worker (CSW) as their first partner and 87% had contact with a CSW
      at some time. Median lifetime number of all partners was 29. In the 6 months
      prior to interview, 35% had two or more partners. Among the currently married,
      23% had CSW contact within the past 6 months; 13% had contact with a nonmarital,
      noncommercial partner; and about 8% reported marital as well as both CSW and
      noncommercial relationships in the same time period. Over half the unmarried
      reported sexual relations in the 6 months; 25% reported contacts with both CSW
      and noncommercial partners. About 40% of subjects visiting CSWs used condoms
      inconsistently or not at all. Drivers were knowledgeable about AIDS and
      prevention measures, with some important misconceptions, but self-assessment of
      risk of HIV showed a negligible sense of their personal vulnerability.

PMID- 9010510
TI  - Predictors of African American adolescents' condom use and HIV risk behavior.
AB  - This study evaluated predictors of risky and safer behavior in a sample of low
      income African American adolescents, assessed their perceptions of the risk
      associated with their sexual behavior, and examined differences between
      adolescents who used condoms consistently, inconsistently, or engaged only in
      unprotected intercourse. African American adolescents (N = 312) completed
      measures related to AIDS knowledge, frequency of condom use, attitudes toward
      condoms, and sexual behavior over the preceding 2 months. Multiple regression
      analyses for the sexually active youths (N = 114) revealed that lower self
      efficacy, higher perceived risk, and male gender were associated with high-risk
      behavior. Positive attitudes toward condoms and younger age had the strongest
      association with condom use. Consistent condom users were more knowledgeable and
      held more positive attitudes toward condoms, and nonusers were older. Regardless
      of their behavior, the adolescents generally did not perceive themselves to be a
      risk for HIV infection. The findings suggest that precautionary practices (condom
      use) and high-risk behavior (unprotected sex with multiple partners) may have
      different correlates. In addition, the data indicate that theoretical models
      developed with homosexual male populations may also be generalizable to African
      American adolescents' sexual behavior.

PMID- 9010511
TI  - Effects of an institutional AIDS prevention intervention: moderation by gender.
AB  - AIDS risk reduction programs are being conducted in many institutional settings,
      but rigorous evaluations of their effectiveness are lacking. This is particularly
      unfortunate in that these programs are expensive, and tend to be of lower
      intensity than those that have been shown to be effective. Further, risk
      reduction is generally regarded as entailing greater difficulty for women, who do
      not use condoms themselves but must negotiate their use with male partners. We
      used a quasi-experimental design to evaluate an institutional AIDS prevention
      program on a New Jersey college campus. Sexual behavior was assessed via linked,
      anonymous mailed surveys at the beginning and end of an academic year among 1st
      year students on the campus and others on a nearby control campus. Responses from
      the spring survey indicated that intervention campus students had been exposed
      significantly more than control students to intervention components. While
      MANCOVA analyses indicated no main effect of treatment group on outcome variable,
      we obtained a significant group by gender interaction, indicating a significant
      effect on number of risky encounters for men but not for women. In fact, relative
      to women on the control campus, women on the intervention campus displayed
      reduced self-efficacy to perform safe sex at the end of the year. These results
      may indicate that although men can be effectively reached by low-intensity risk
      reduction programs, women may not be. In fact, interventions without adequate
      intensity to provide substantial and individualized negotiation skill training
      may cause women to experience failure in these efforts.

PMID- 9010512
TI  - HIV seropositive gay men: understanding adoption of safe sexual practices.
AB  - The aim of this study was to determine the best predictors of safe sex practices
      among HIV seropositive gay men. A group of 96 homosexual men living with HIV
      completed a questionnaire that investigated theoretical constructs of the Ajzen's
      (1988) theory of planned behavior with respect to condom use for anal intercourse
      and sexual practices without anal intercourse. Other variables such as Triandis's
      (1977) construct of personal normative belief, psychological distress, and
      alcohol and drug use before sexual encounters were also investigated. Results
      indicated that the best predictor of intention to use condoms was perceived
      behavioral control. Personal normative belief was another important predictor of
      this intention. Although the best predictor of intention to have only sex without
      anal intercourse was perceived subjective norm, this intention was also
      significantly explained by perceived behavioral control. Moreover, perceived
      behavioral control was a significant predictor of having only sex without anal
      intercourse. Public health interventions among HIV seropositive gay men should
      aim mainly at increasing perception of behavioral control.

PMID- 9010513
TI  - Differences between gay men in primary relationships and single men: implications
      for prevention.
AB  - This study describes psychological and behavioral differences between gay men in
      primary relationships and single men from 1985 through 1989. In addition,
      differences in sexual behavior, relationship status, and relationship quality
      between HIV positive and HIV negative men were investigated. Data are from the
      San Francisco Men's Health Study and included only men who were gay identified
      and who participated in the longitudinal surveys in 1985, 1987 and 1989 (N =
      452). Participants were stratified by relationship status and by HIV status. HIV
      positive men were less likely than HIV negative men to be in primary
      relationships (38.9% vs. 52.9%, respectively in 1989). In addition, men in
      relationships had higher rates of unprotected anal intercourse than single men
      (32.6% vs. 17.0%, respectively in 1989). Differences in psychosocial and
      behavioral variables were found and have considerable implications for prevention
      programs and mental health services trying to meet the needs of the gay men's
      community.

PMID- 9010515
TI  - Hippocampal volume in normal aging and traumatic brain injury.
AB  - PURPOSE: To present a normative database of hippocampal and temporal horn volume
      and to clarify the relationship between these measures and cognitive outcome in
      patients with traumatic brain injury. METHODS: Ninety-six healthy volunteers and
      94 patients with traumatic brain injury were examined with coronal intermediate
      and T2-weighted MR imaging. Multispectral segmentation and volume analyses were
      performed. The volumetry of the hippocampus and temporal horn was characterized
      in the control subjects. Volumetric measures in a group of patients with
      traumatic brain injury who had received MR imaging 3 months or less after injury
      were compared with measurements in other patients in the chronic phase of
      recovery. The relationship between neuropsychological testing and volumetric
      measures was analyzed with particular emphasis on the correlation between
      cognitive outcome and hippocampal and temporal horn volumes. RESULTS: No
      significant age group differences were found in the normative group from age 16
      to 65. Left and right hippocampal volumes were interrelated and did not differ
      from each other. This was also true for the temporal horns. Hippocampal and
      temporal horn volumes were not significantly related. Women had larger hippocampi
      relative to cranial volume. Comparisons between patients with traumatic brain
      injury and control subjects showed significant yet modest bilateral atrophic
      changes in hippocampal and temporal horn enlargement in the patients with brain
      injury. Hippocampal and temporal horn volumes correlated significantly with each
      other in the group with traumatic brain injury. Cognitive outcome was modestly
      related to hippocampal and temporal horn volumes. However, in a specific subgroup
      whose images were acquired between 71 and 210 days after injury, strong
      correlations were noted in which temporal horn volume correlated highly with IQ
      and hippocampal volume correlated with verbal memory function. CONCLUSION:
      Hippocampal and temporal horn volumes appear to be independent variables in
      healthy control subjects. Traumatic brain injury results in significant
      hippocampal atrophy and temporal horn enlargement. The hippocampus and temporal
      horn volumes were inversely correlated in the group with traumatic brain injury,
      suggesting a differential relationship of these structures in patients with brain
      injury as compared with control subjects. In the subacute phase, the volume of
      the temporal horn may be indicative of intellectual outcome and that of the
      hippocampus appears to be indicative of verbal memory function.

PMID- 9010514
TI  - MR-based brain and cerebrospinal fluid measurement after traumatic brain injury:
      correlation with neuropsychological outcome.
AB  - PURPOSE: To determine the magnitude and time course of changes in the volume of
      brain and intracranial cerebrospinal fluid (CSF) spaces in patients who have
      sustained traumatic brain injury and to assess the relationship between these
      findings and long-term cognitive traumatic outcome. METHODS: Axial intermediate
      and T2-weighted MR images of 123 patients with traumatic brain injury were
      quantified using a multispectral segmentation algorithm. Measurements were
      corrected for differences in age, sex, and head size using a previously reported
      normative database. Brain morphology was compared across groups formed on the
      basis of chronicity of injury. Cognitive functioning and severity of injury were
      statistically correlated with brain measurements. RESULTS: Time-dependent
      expansion of CSF spaces and decreases in brain volume were observed. Increases in
      ventricular CSF volume, particularly in the temporal horns and third ventricle,
      preceded subsequent changes in total brain and subarachnoid CSF. High and
      moderate correlation was observed between volume measures and cognitive outcome
      and injury severity. Particularly strong was the relation between the volume of
      the left temporal horn and verbal IQ scores. CONCLUSION: Predictable time
      dependent atrophic changes occurring after traumatic brain injury can be
      quantified using MR volumetric studies. Our results suggest significant
      contributions by both diffuse and focal mechanisms of injury. In the postacute
      period (more than 70 days after injury), MR volumetric studies may be predictive
      of eventual cognitive outcome.

PMID- 9010516
TI  - Medial temporal lobe volumetrics in traumatic brain injury.

PMID- 9010517
TI  - The nature of thrombosis induced by platinum and tungsten coils in saccular
      aneurysms.
AB  - PURPOSE: To compare the efficacy and biocompatability of electrolytic and
      mechanically detachable embolization coils of two metal types. METHODS:
      Experimental saccular aneurysms in pigs were used to assess embolization induced
      by platinum or tungsten coils. Longitudinal angiographic and histologic studies
      were performed on treated and untreated (control) aneurysms to compare thrombosis
      and cellular responses after embolization with electrolytically detachable
      platinum coils and with mechanically detached tungsten coils. RESULTS: Fewer
      tungsten than platinum coils were needed to induce thrombosis. The inflammatory
      response within the aneurysmal lumen was more florid in embolized aneurysms than
      in control aneurysms. No difference was found in the timing or extent of
      accumulation of eosinophils, lymphocytes, or polymorphs between the two coils
      used. Giant cell responses were more marked in treated aneurysms; tungsten coils
      more than platinum coils. The amount of collagen and fibrosis present increased
      over the study period and was similar in treated and control aneurysms.
      CONCLUSION: The coil type influenced the initial cellular response but had little
      effect on the rate or degree to which blood clot within the aneurysm was replaced
      by fibrous tissue.

PMID- 9010518
TI  - Long-term angiographic and histopathologic findings in experimental aneurysms of
      the carotid bifurcation embolized with platinum and tungsten coils.
AB  - PURPOSE: To evaluate the long-term outcome of endovascular occlusion of arterial
      aneurysms effected with metal coils. METHODS: Microsurgical methods were used to
      produce carotid bifurcation aneurysms in 20 rabbits and the radiologic and
      histologic changes were examined. Eight of these aneurysms were occluded with
      electrically detachable platinum coils (Guglielmi detachable coils [GDCs] and
      nine were treated with mechanically detachable tungsten coils (mechanical
      detachable system [MDS]). Three aneurysms remained untreated and served as
      controls. One animal died of embolic complications 12 hours after endovascular
      treatment. After observation periods of 3 to 6 months, the remaining animals were
      examined by intraarterial digital subtraction angiography and subsequent fixation
      and light and electron microscopy. RESULTS: Large open spaces without signs of
      thrombosis were found between the loops of the coil baskets in 12 aneurysms (six
      treated with GDCs and six treated with MDS) regardless of the observation period.
      In very densely packed aneurysms (four cases with complete occlusion as
      determined by angiographic criteria), the coil surfaces were for the most part
      covered by thin cell layers; however, complete endothelialization was never seen.
      In aneurysms with an initial partial occlusion of 70% to 90%, coil compaction
      and/or recanalization was a consistent finding. A comparison of the radiologic
      findings with the histologic aspect revealed that the degree of occlusion was
      often overrated on the radiographs (in eight of 17 cases). In general, the
      fibrous tissue reaction appeared to be slightly more pronounced in aneurysms
      occluded with tungsten coils. CONCLUSIONS: Platinum and tungsten coils were not
      always effective in causing endoluminal thrombosis leading to long-term occlusion
      by organized thrombus.

PMID- 9010519
TI  - Coil embolization of aneurysms: angiographic and histologic changes.

PMID- 9010520
TI  - MR of the endolymphatic duct and sac: findings in Meniere disease.
AB  - PURPOSE: To compare the visibility of the endolymphatic duct and sac on high
      resolution MR images with the symptoms and clinical course in patients with
      Meniere disease. METHODS: Twenty-two patients with unilateral Meniere disease
      were sorted into two groups on the basis of the clinical stage of their disease
      at the time of imaging. Group 1 included patients in the acute phase, who
      presented with vertigo. Group 2 comprised patients in the nonacute phase of the
      disease, who were studied 9 days or more after an episode of vertigo. RESULTS:
      During acute attacks, the endolymphatic duct and sac were not adequately visible
      in the affected ear but were visible in the unaffected ear. During remission, the
      endolymphatic duct and sac were not observed in clinically advanced patients, but
      they were seen in patients in the early and intermediate stages. CONCLUSION: High
      resolution MR imaging can be used to evaluate the endolymphatic duct and sac:
      visible abnormalities and lack of a visible endolymphatic duct and sac correlate
      with the clinical course of Meniere disease.

PMID- 9010521
TI  - High-resolution CT of the temporal bone in dysplasia of the auricle and external
      auditory canal.
AB  - PURPOSE: To determine CT findings in the external, middle, and inner ear of
      patients with microtia and external auditory canal dysplasia. METHODS: We used
      high-resolution CT, with multiplanar or axial 1-mm continuous sections, coronal
      or sagittal reformations, or low-dose spiral acquisitions, to examine 184
      temporal bones of children with microtia. RESULTS: In cases of minor microtia,
      auditory canal stenosis was the most common associated abnormality; in those with
      major microtia, atresia was predominant. Middle ear malformations depended on the
      severity of the auricular anomalies. Inner ear changes could also be noted.
      Ossicle dysplasias occurred in 98% of patients (stapes, 72%), absence of the oval
      window in 36%, labyrinthine malformations in 13%, closed round window in 6%,
      facial canal displacement in up to 75%, and aberrations of the vascular canal in
      38% of patients with third-grade auricular deformity. CONCLUSION: A variety of
      external, middle, and, less frequently, inner ear changes were detected in
      connection with microtia.

PMID- 9010522
TI  - Overlapping thin-section fast spin-echo MR of the large vestibular aqueduct
      syndrome.
AB  - PURPOSE: To evaluate a high-resolution, thin-section fast spin-echo MR imaging
      technique of the inner ear to identify the large vestibular aqueduct syndrome
      seen on temporal bone CT scans. METHODS: We retrospectively reviewed the temporal
      bone CT scans of 21 patients with hearing loss and enlarged bony vestibular
      aqueducts by CT criteria. High-resolution fast spin-echo MR imaging was then
      performed on these patients using dual 3-inch phased-array receiver coils fixed
      in a temporomandibular joint holder and centered over the temporal bones. MR
      imaging included axial and oblique sagittal fast spin-echo sequences. The
      diameter of the midvestibular aqueduct on CT scans and the signal at the level of
      the midaqueduct on MR images were measured on axial sequences, then compared.
      High-resolution MR imaging with the same protocol was performed in 44 control
      subjects with normal ears, and similar measurements were taken. RESULTS: The
      average size of the enlarged bony vestibular aqueduct on CT scans was 3.7 mm, and
      the average width of the signal from within the enlarged aqueduct on MR images
      was 3.8 mm. Statistical analysis showed excellent correlation. MR images alone
      displayed the enlarged extraosseous endolymphatic sac, which accompanies the
      enlarged aqueduct in this syndrome. Five ears in three patients with enlarged
      bony vestibular aqueducts on CT scans showed no evidence of an enlarged
      endolymphatic duct or sac on MR images. An enlarged endolymphatic sac was seen on
      MR images in one patient with a bony vestibular aqueduct, which had normal
      measurements on CT scans. MR imaging alone identified a single case of mild
      cochlear dysplasia (Mondini malformation). In the 88 normal ears studied, the
      average size of the endolymphatic sac at its midpoint between the common crus and
      the external aperture measured on MR images was 0.8 mm (range, 0.5 to 1.4 mm). In
      25% of the normal ears, no signal was seen from within the vestibular aqueduct.
      CONCLUSION: Thin-section, high-resolution fast spin-echo MR imaging of the inner
      ear is complementary to CT in studying patients with the large vestibular
      aqueduct syndrome, as MR imaging better displays the soft tissue and fluid of the
      membranous labyrinth.

PMID- 9010523
TI  - MR differentiation of adamantinous and squamous-papillary craniopharyngiomas.
AB  - PURPOSE: To determine MR criteria for differentiating adamantinous from squamous
      papillary craniopharyngiomas. METHODS: The MR imaging features of 42
      histologically proved craniopharyngiomas (25 adamantinous, 15 squamous-papillary,
      and two mixed subtypes) were examined with multiplanar T2-weighted and
      noncontrast and contrast-enhanced T1-weighted imaging. Differences in the mR
      features of both subtypes were evaluated retrospectively. RESULTS: The
      adamantinous craniopharyngioma is a mixed solid-cystic or mainly cystic lobulated
      suprasellar or intrasellar/suprasellar tumor occurring in children and adults,
      typically with large nonenhancing hyperintense cysts on T1-weighted images. The
      squamous-papillary craniopharyngioma is a predominantly solid or mixed solid
      cystic suprasellar tumor occurring in adults, appearing as a hypointense cyst on
      noncontrast T1-weighted images. Calcifications and recurrent tumors are more
      often observed in adamantinous tumors but can be seen in squamous-papillary
      tumors as well. Statistically significant parameters useful for differentiating
      the two tumor subtypes are the encasement of vessels, the lobulated shape, and
      the presence of hyperintense cysts in adamantinous tumors, and the round shape,
      the presence of hypointense cysts, and the predominantly solid appearance in
      squamous-papillary tumors. CONCLUSION: Craniopharyngiomas can be divided into two
      clinically, histologically different subtypes, which suggests a different
      pathogenesis of these two types of tumor.

PMID- 9010524
TI  - High signal intensity of the infundibular stalk on fluid-attenuated inversion
      recovery MR.
AB  - PURPOSE: To determine the MR imaging characteristics of the pituitary stalk with
      a fluid-attenuated inversion recovery (FLAIR) technique. METHODS: We
      retrospectively studied the prevalence of a high-signal infundibular stalk on
      FLAIR MR images of the brain in 133 patients and compared this finding with the
      patients' ages. To understand the cause of the high signal intensity of the
      pituitary stalk on FLAIR images, we calculated the T1, T2, and proton-density
      values in regions of gray matter, white matter, and the pituitary stalk in nine
      cases. RESULTS: FLAIR images showed the pituitary stalk as having high signal
      intensity in 97 (73%) of 133 cases; however, in 11 of 16 patients less than 10
      years old, the infundibular stalk was not of high signal intensity. In patients
      with a high-signal pituitary stalk on FLAIR images, the T2 value of the pituitary
      stalk was longer than that of gray or white matter. CONCLUSION: High signal
      intensity of the infundibular stalk was frequently seen on FLAIR MR images of the
      brain at all ages. A prolonged T2 value of the pituitary stalk caused the high
      signal intensity, presumably reflecting the fluid component of the pituitary
      stalk.

PMID- 9010525
TI  - Involvement of the pontomedullary corticospinal tracts: a useful finding in the
      diagnosis of X-linked adrenoleukodystrophy.
AB  - PURPOSE: To determine whether pontomedullary corticospinal tract involvement is a
      common and specific finding of adrenoleukodystrophy on MR images. METHODS: MR
      images of 10 patients with biochemically proved adrenoleukodystrophy who were
      examined during the last 6 years were reviewed retrospectively to determine the
      frequency of corticospinal tract involvement in the medulla, pons, mesencephalon,
      internal capsules, and corona radiata. MR images of 10 patients with other
      leukodystrophies (three with Krabbe disease, two with Alexander disease, two with
      metachromatic leukodystrophy, two with Pelizaeus-Merzbacher disease, and one with
      Canavan disease) were reviewed with specific attention to the pontomedullary
      corticospinal tracts. RESULTS: Medullary and pontine corticospinal tract
      involvement was present in eight of the 10 patients with adrenoleukodystrophy.
      Mesencephalic and internal capsular involvement was present in three patients.
      The coronal radiata portion of the corticospinal tracts was not involved in any
      of the 10 patients. No pontomedullary corticospinal tract involvement was
      identified in any of the 10 patients with other leukodystrophies. The difference
      in the frequency of pontomedullary corticospinal tract involvement between the
      two groups was highly significant. CONCLUSION: Pontomedullary corticospinal tract
      involvement is a common finding in adrenoleukodystrophy and is unusual in other
      leukodystrophies. Awareness of this finding can facilitate the radiologic
      diagnosis of this disease and may expedite management of affected patients.

PMID- 9010526
TI  - Hypertensive encephalopathy in children.
AB  - We present five cases of hypertensive encephalopathy in children, three with MR
      imaging findings and two with CT findings alone. One of the five patients had MR
      perfusion imaging, which showed perfusion abnormalities that support the concept
      of vasodilation as the major contributor to the syndrome. Hypertensive
      encephalopathy is rarely reported in children, and its true prevalence may be
      underestimated. Characteristic lesions in the severely hypertensive child should
      be recognized as manifestations of hypertensive encephalopathy, and subsequent
      clinical management should focus on treatment of the hypertension and/or its
      underlying causes.

PMID- 9010527
TI  - Central nervous system cryptococcosis: parenchymal calcification and large
      gelatinous pseudocysts.
AB  - In an 11-year-old immunocompetent girl with protracted cryptococcal infection of
      the central nervous system, CT showed multiple areas of parenchymal
      calcification. MR imaging showed large gelatinous pseudocysts around the brain
      stem. These imaging features and the child's age are unusual for intracranial
      cryptococcosis.

PMID- 9010528
TI  - Anatomic relationship of the oculomotor nuclear complex and medial longitudinal
      fasciculus in the midbrain.
AB  - PURPOSE: To compare the MR characteristics of the oculomotor nucleus with its
      appearance on anatomic images. METHODS: Specimens of cadaveric brains were imaged
      in a 3.0-T MR imager equipped with a 3.0-cm solenoid coil. The specimens were
      sectioned, stained, and examined histologically. On anatomic sections, the
      oculomotor nuclei, medial longitudinal fasciculus, red nuclei, and oculomotor
      nerve were identified. The MR images were then compared with the anatomic
      sections. RESULTS: The oculomotor nuclei, medial longitudinal fasciculus, red
      nuclei, and oculomotor nerve could be identified on MR images by their size,
      shape, signal intensity, and location. CONCLUSION: MR images show the anatomic
      relationship of the oculomotor nerve complex, medial longitudinal fasciculus, and
      related structures in the brain stem.

PMID- 9010529
TI  - Tissue segmentation of the brain in Alzheimer disease.
AB  - PURPOSE: To compare brain tissue in patients with Alzheimer disease with that in
      elderly control subjects by using high-resolution MR imaging and quantitative
      tissue-segmentation techniques. METHODS: MR imaging of the brain was performed in
      21 patients with Alzheimer disease and 17 control subjects. A computerized
      segmentation program was used to quantify volumes of ventricular and sulcal
      cerebrospinal fluid (CSF), white matter, cortical gray matter, and white matter
      signal hyperintensity. Statistical analysis was performed using analysis of
      variance. RESULTS: We found a significant decrease in total brain tissue and
      cortical gray matter and an increase in the ventricular and sulcal CSF in
      Alzheimer patients compared with control subjects. There was no difference in the
      volume of white matter. More white matter signal hyperintensities were found in
      Alzheimer patients, and a significant interaction between age and group was
      noted. Neuropsychological test scores correlated significantly with sulcal CSF in
      patients with Alzheimer disease. CONCLUSION: Semiautomated segmentation of MR
      images of the brains of patients with Alzheimer disease reveals significant brain
      atrophy attributable to loss of cortical gray matter, which is compatible with
      the pathologic features of Alzheimer disease. There is also a significant
      increase in white matter signal hyperintensities. Tissue segmentation may
      increase our understanding of dementia but, as yet, when used alone, it does not
      play a role in the premorbid diagnosis of Alzheimer disease.

PMID- 9010530
TI  - Cortical and subcortical T2 shortening in multiple sclerosis.
AB  - Low signal intensity on long-repetition-time MR sequences has been observed in
      deep gray matter structures in patients with multiple sclerosis. This T2
      shortening most likely represents a nonspecific degenerative process. We recently
      observed T2 shortening in the pericentral cortical gray matter and subcortical
      white matter in a patient with severe multiple sclerosis and we postulate that
      this represents an additional manifestation of neural degeneration.

PMID- 9010531
TI  - Transcranial color-coded duplex sonography in the evaluation of collateral flow
      through the circle of Willis.
AB  - PURPOSE: To determine the sensitivity, specificity, and positive and negative
      predictive values of transcranial color-coded duplex sonographic (TCCD)
      evaluation of cross flow through the anterior (ACoA) and posterior (PCoA)
      communicating arteries in patients with occlusive cerebrovascular disease.
      METHODS: We studied prospectively 132 patients (37 women, 95 men; mean age, 60
      years) with stenoses of more than 69% reduction in vessel diameter (n = 93) and
      occlusions (n = 52) of the internal carotid artery, and three occlusions of the
      basilar artery. The sonographer was aware of extracranial sonographic findings
      but was blinded to the results of cerebral angiography. RESULTS: Nine patients
      (7%) with thick bones preventing transtemporal insonation and three patients (3%)
      with occlusions of the middle (n = 3) and anterior (n = 1) cerebral arteries were
      excluded. Sensitivity of TCCD for detection of collateral flow through the ACoA
      in patients with occlusive carotid artery disease was 98%, specificity was 100%,
      positive predictive value was 100%, and negative predictive value was 98%. The
      corresponding values for the PCoA were 84%, 94%, 94%, and 84%, respectively. All
      three functional PCoAs were identified in patients with occluded basilar
      arteries. CONCLUSION: TCCD is a valuable method for noninvasive evaluation of
      cross flow through the ACoA in patients with adequate sonographic windows.
      However, TCCD evaluation of cross flow through the PCoA is less reliable, because
      hemodynamic criteria may cause falsely positive and falsely negative results.

PMID- 9010532
TI  - Intracranial vascular stenosis and occlusion: MR angiographic findings.
AB  - PURPOSE: To investigate whether obtaining axial source images from three
      dimensional Fourier transform (3DFT) time-of-flight MR angiography improves the
      detection of intracranial vascular stenosis and occlusion if added to maximum
      intensity projection (MIP) images. METHODS: The angiograms of 103 patients who
      had MR angiography for evaluation of possible intracranial vascular disease were
      reviewed retrospectively in a quantitative and nonquantitative fashion. Diameters
      of vessels on MR angiograms were measured quantitatively by two reviewers using a
      magnifying loupe and compared with the results from conventional angiograms.
      Degrees of stenoocclusive disease were categorized into five classes; an artery
      with stenosis of 50% or greater was considered to be diseased. Another five
      observers also reviewed the MIP images with and without source images in a
      blinded fashion by means of nonquantitative visual inspection. RESULTS: In all,
      23 stenoocclusive lesions of 50% or greater were available for review. In the
      quantitative analysis, with MIP images alone, 14 (78%) of 18 moderate and severe
      stenoses and four (80%) of five occlusions were identified correctly. The
      addition of the source images increased the sensitivity to 100% for moderate and
      severe stenoses and to 100% for occluded vessels. In the visual inspection study,
      however, no statistically significant differences were found between
      interpretations of MIP images alone and those of MIP images in combination with
      source images. CONCLUSION: In the quantitative study, interpretation of source
      images rather than MIP images reduced the tendency to overestimate stenosis seen
      with MR angiography and improved the sensitivity for detecting stenosis of 50% or
      greater. There was a discrepancy between the quantitative study and visual
      inspection. Experienced observers had a tendency to underestimate the degree of
      stenosis.

PMID- 9010533
TI  - Arterial vascular abnormality accompanying cerebral cortical dysplasia.
AB  - We report a case of dysplastic arterial vascular abnormality in a 32-year-old man
      with overlying neuronal cell migration disorder. MR images showed a thickened
      left insular cortex adjacent to the abnormal vascular network. These findings
      suggest the possibility of leptomeningeal damage during neuronal cell migration
      as the cause of the overlying vasculopathy. The true pathogenesis of these
      seemingly associated abnormalities is unknown.

PMID- 9010534
TI  - Magnetization transfer effects on T1-weighted three-dimensional gradient-echo MR
      images of a phantom simulating enhancing brain lesions.
AB  - PURPOSE: To develop a simple tissue phantom to study the effects of various
      imaging parameters and gadolinium concentrations on magnetization transfer (MT)
      and lesion-to-background ratios. METHODS: A commercial egg product was doped with
      gadolinium in concentrations of 0.0 to 1.0 mmol/L and cooked. The T1 and T2
      values were determined for the phantom materials and for the white and gray
      matter of a healthy volunteer subject. The gadolinium-doped egg phantom and human
      brain were studied using a short-repetition-time three-dimensional gradient-echo
      MT sequence with various effective MT powers, frequency offsets, and section
      select flip angles. The normalized signal intensities, MT ratios (MTRs), and
      simulated lesion-to-background normal white matter contrast ratios were
      determined for a variety of experimental conditions. RESULTS: The MTR and lesion
      to-background contrast ratios for all materials were greatest at the highest
      effective MT power (270 Hz, root-mean-square of amplitude) and the narrowest MT
      pulse frequency offset (1000 Hz). There was an inverse relationship between
      gadolinium concentration and MTR, and a positive relationship between the
      gadolinium concentration and lesion-to-background contrast. MTR was greatest at
      low flip angles, where there was little T1 weighting. The simulated lesion-to
      background contrast showed a complex, gadolinium concentration-dependent
      relationship with section excitation flip angle. CONCLUSIONS: The tissue phantom
      has relaxation properties and MT behavior close to that expected for enhancing
      brain lesions, allowing a rigorous analysis of simulated lesion-to-background
      contrast for high MT power, short-repetition-time, three-dimensional gradient
      echo sequences.

PMID- 9010536
TI  - High-resolution MR of the intraparotid facial nerve and parotid duct.
AB  - PURPOSE: To describe a high-resolution MR imaging technique that depicts the
      complex anatomy of the region of the parotid gland, focusing on the intraparotid
      components of the facial nerve and parotid duct. METHODS: High-resolution T1
      weighted images of the parotid gland were acquired with a prototype three
      dimensional Fourier transform gradient-echo sequence that permits a very short
      echo time (4.2 milliseconds) by using a modified phase-encoded time-reduced
      acquisition scheme. The sequences were obtained at 1.5 T with a head and neck
      coil. Postprocessed multiplanar, curved and volumetric images were obtained. The
      most clinically useful images were acquired at parameters of 40/4.2 (TR/TEeff) a
      flip of 30 degrees, a field of view of 18 to 20 cm, a matrix of 512 x 288 or 512
      x 256, an axial plane, 60 images, no gaps, and a section thickness of 1.5 mm.
      Eighteen healthy subjects were examined. The position of the facial nerve within
      the parotid gland was determined by identifying the facial nerve in the
      stylomastoid foramen and then following it on sequential sections through the
      parotid gland. Curved reformations were used to confirm the visibility of the
      nerve. A similar technique was used for the parotid duct. RESULTS: The image
      contrast obtained was similar to that of standard spin-echo T1-weighted images.
      The parotid gland showed intermediate signal intensity while the fat spaces
      showed high signal intensity. The vessels had variable signal intensity depending
      on saturation. The cerebrospinal fluid, nerves, muscles, and ducts had lower
      signal intensity. In all 18 subjects, the facial nerve from the brain stem to the
      parotid gland, and the parotid duct from the mouth to the hilus of the gland were
      seen bilaterally. The proximal intraparotid facial nerve to the level of the
      retromandibular vein was seen in 72% of the subjects and the main intraparotid
      ducts were seen in 66% of the subjects. CONCLUSION: High-resolution MR imaging
      offers simultaneous display of most of the important structures in the region of
      the parotid gland, including the intraparotid duct and facial nerve.

PMID- 9010535
TI  - Normal contrast enhancement of extraocular muscles: fat-suppressed MR findings.
AB  - PURPOSE: To evaluate contrast enhancement of normal extraocular muscles in the
      orbit. METHODS: Noncontrast and contrast-enhanced T1-weighted images of the orbit
      were acquired using a fat-suppression MR technique in eight patients with no
      orbital disease. Contrast enhancement of 64 extraocular muscles was evaluated and
      compared with that of 16 temporal muscles. RESULTS: Compared with temporal
      muscles, all extraocular muscles markedly enhanced after administration of
      contrast material. CONCLUSIONS: Because normal extraocular muscles enhanced
      markedly with contrast material, more attention should be paid to these muscles
      when using contrast-enhanced, fat-suppressed T1-weighted MR imaging to evaluate
      pathologic conditions.

PMID- 9010537
TI  - Adenosquamous carcinoma of the facial bones, skull base, and calvaria: CT and MR
      manifestations.
AB  - A 62-year-old woman had proptosis of the right eye, decreased visual acuity of
      the left eye, and no other focal neurologic deficits. She had a grand mal seizure
      1 month before admission. The CT and MR studies showed extensive bone destruction
      of the margins of the right orbit, the floor of the middle cranial fossa, the
      right cavernous sinus, and much of the calvaria. There was considerable dural
      disease and tumor in the right orbit, paranasal sinuses, and scalp, as well as
      mucoceles of the left ethmoidal sinus with desiccated secretions. The diagnosis
      was adenosquamous carcinoma, an aggressive tumor related to both squamous cell
      carcinoma and adenocarcinoma.

PMID- 9010538
TI  - Heterotopic brain in the pterygopalatine fossa.
AB  - Heterotopic brain outside the cranial vault is uncommon. It occurs most
      frequently in the nasal region, although rests elsewhere in the aerodigestive
      tract have been reported. We describe a case of heterotopic brain in the
      pterygopalatine fossa.

PMID- 9010539
TI  - MR of spinal meningeal melanocytoma.
AB  - We report an unusual case of meningeal melanocytoma, a rare pigmented lesion of
      the leptomeninges, that occurred within the leptomeninges of the thoracic spinal
      canal. The lesion showed increased signal intensity on T1-weighted MR images
      relative to gray matter, was isointense with gray matter on T2-weighted images,
      and enhanced mildly but homogeneously after administration of contrast material.

PMID- 9010540
TI  - John Strainer, 1996 recipient of the Cornelius Dyke Award.

PMID- 9010541
TI  - Polyvinyl alcohol particle superficial morphology.

PMID- 9010542
TI  - Location of pyramidal and spinothalamic tracts.

PMID- 9010543
TI  - Annotated bibliography.

PMID- 9010545
TI  - Low dose of ethanol induces conditioned place preference in rats after repeated
      exposures to ethanol or saline injections.
AB  - Using the place conditioning paradigm (biased design), we have shown that five
      conditioning sessions with ethanol (0.5 or 1.0 g/kg i.p.) did not result in place
      conditioning response. In contrast, rats that received 20 injections of ethanol
      (0.5 g/kg) or saline, before the conditioning procedure, showed significant place
      preference to the compartment paired with 0.5 g/kg ethanol (but not 1.0 g/kg).

PMID- 9010544
TI  - Relative and combined effects of propylthiouracil, ethanol and protein deficiency
      on liver histology and hepatic iron, zinc, manganese and copper contents.
AB  - The present study was performed in order to discern the effects of
      propylthiouracil (PTU) on ethanol and/or protein deficiency-mediated liver
      histological changes and liver Fe, Zn, Cu and Mn alterations in male adult Wistar
      rats. The study was performed on 64 animals divided into eight groups, fed with
      the Leiber-DeCarli control, 36% ethanol-2% protein- and 36% ethanol-2% protein
      containing diets, without and with PTU, respectively. PTU was administered at a
      concentration of 0.05%, an amount which rendered the animals hypothyroid. Two
      further groups of 5 animals each, with and without PTU respectively, were allowed
      to consume the control diet ad libitum. Animals treated with PTU showed
      significantly less fibrosis, but more fat, than animals without PTU. Liver
      fibrosis was inversely correlated with liver zinc, liver content of this element
      being higher in the PTU-treated and the ethanol or protein deficiency groups. PTU
      also reversed ethanol-mediated hepatocyte ballooning and also led to a reduction
      in nuclear areas.

PMID- 9010546
TI  - Aldehyde dehydrogenase activity and acetate production by aerobic bacteria
      representing the normal flora of human large intestine.
AB  - We have recently proposed the existence of a bacteriological pathway for ethanol
      oxidation, i.e. ethanol is oxidized by alcohol dehydrogenase of intestinal
      bacteria resulting in high intracolonic levels of reactive and toxic
      acetaldehyde. This study was aimed to examine aldehyde dehydrogenase (ALDH)
      activity, acetaldehyde consumption and production of acetate by aerobic bacteria
      (n = 27), representing the normal human colonic flora. Most bacterial strains did
      not show any membrane-associated aldehyde dehydrogenase, but possessed marked
      cytosolic NADP(+) - and NAD(+) - dependent aldehyde dehydrogenase activity,
      ranging from 155 nmol of NAD(P)H produced/min/mg of protein to zero with
      acetaldehyde as substrate. NADP(+)-linked ALDH activity was significantly higher
      than NAD(+)-linked activity in most of the tested bacteria. In addition, aerobic
      bacteria metabolized acetaldehyde effectively in vitro and this could be
      inhibited by cyanamide in nearly half of the tested strains. Production of
      acetate from acetaldehyde ranged from 2420 nmol/10(9) colony-forming units to
      almost negligible. In conclusion, many human aerobic colonic bacteria possess
      significant aldehyde dehydrogenase activity and can, consequently, produce
      acetate from acetaldehyde in vitro at least under the partially aerobic
      conditions proposed to prevail on the colonic mucosal surface. Individual
      variation in the capability of colonic flora to remove toxic acetaldehyde may be
      one factor regulating intracolonic acetaldehyde levels, as well as the rate of
      bacteriocolonic pathway for ethanol oxidation.

PMID- 9010547
TI  - The SECCAT survey: I. The costs and consequences of alcoholism.
AB  - The SECCAT survey assessed the Socio-Economic Costs and Consequences of
      Alcoholism Treatment. Basic demographic and health service resource use data (for
      a previous 6-month period) were obtained fro a cohort of 586 eligible patients
      who had had treatment at the Alcohol Problems Clinic (APC) in Edinburgh. The
      cohort was 75% male with a mean age of 46.0 years. Seventy-six per cent had an
      initial diagnosis of alcohol dependence and 21% alcohol abuse. Use of health
      services was highly variable. Thirty-six per cent agreed to be interviewed to
      provide data on their level of abstinence, on resource use, on quality of life
      (SF-36), on socio-economic characteristics and key adverse events. These 212
      individuals had similar age and sex ratios to the full cohort, but alcohol
      abusers were under-represented. Nineteen patients reported no days of abstinence
      and 41 were abstinent over the whole 6-month period. Patients experienced a much
      poorer quality of life than a normal population in terms of all dimensions of the
      SF-36. The average total health care costs of the interviewed patients were 1134
      pounds of which 38% were related to treatment at the APC. Analysis suggests that
      alcohol-dependent patients make substantially more costly use of resources than
      abusers and experience a much poorer quality of life. No clear relationship of
      cost to degree of abstinence has been found. There is a clear and consistent
      relationship of SF-36 scores and drinking behavior.

PMID- 9010548
TI  - Moderating binge drinking: it is possible to change behaviour if you plan it in
      advance.
AB  - Recent theories of enactment suggest that behaviour change is increased by
      planning how, where, and when to execute a behavioural response. Drawing on these
      theories, a brief planning intervention was designed and its effectiveness
      compared to an information-based health promotion programme (control). All
      participants were given information about the safe limits per drinking occasion
      and the adverse consequences of binge drinking, and were asked to drink within
      the safe limits in order to avoid these consequences. In addition, participants
      in the planning group received an option menu of possible responses for refusing
      a drink, asked to choose one strategy and specify a time and place in which the
      chosen strategy would be implemented. The planning intervention group did not
      differ from the control group on reported likelihood of future binge drinking,
      nor on levels of past drinking, age and gender. At a 2-week follow-up, members of
      the planning intervention group reported lower drinking frequency than controls.
      The implications of prior planning for interventions aimed at reducing alcohol
      related harm are discussed.

PMID- 9010550
TI  - Identifying hazardous or harmful alcohol use in medical admissions: a comparison
      of audit, cage and brief mast.
AB  - Two hundred and forty new medical inpatients received Alcohol Use Disorders
      Identification Test (AUDIT), CAGE and brief Michigan Alcoholism Screening Test
      (brief MAST) questionnaires. Sensitivities when identifying weekly drinkers of >
      14 units (women) or > 21 units (men) were 93, 79 and 35%, respectively (P <
      0.001). Sensitivities to > 21 units (women) or > 28 units (men were 100%, 94% and
      47%. Routine screening of medical admissions with the AUDIT (cut-off score 8) is
      recommended.

PMID- 9010549
TI  - Validity of self-reported criminal offences and traffic violations in screening
      of driving-while-intoxicated offenders.
AB  - Many jurisdictions in the USA, Canada and some European countries use diagnostic
      methods to assess substance abuse problems of driving-while-intoxicated (DWI)
      offenders, to address the concern that, during DWI screening, offenders may not
      give accurate information on their criminal history and traffic violations to
      avoid referral to treatment. This study was designed to validate self-reported
      data, to assess the need for DWI agencies to access court records, and to obtain
      an offence profile for this population. DWI offenders (n = 274, mostly first
      time) were randomly selected from those who attended the Lovelace Comprehensive
      Screening Program (LCSP). The self-reported data were compared with records
      retrieved from the Metropolitan Court in Albuquerque, New Mexico, USA. Three
      quarters of the offenders had had at least one offence or traffic violation
      before this DWI arrest. Sixty-five per cent of the offenders with court records
      underreported their records. The high percentage of false self-reporting for a
      primarily first-time offender population indicates the need to use court records
      to verify self-reported data. For multiple offenders, who have a much higher rate
      of criminal offences and traffic violations, checking self-reported data against
      court records becomes more important. In addition, a questionnaire based on
      offence information could be used to obtain a more complete history of those
      offences.

PMID- 9010551
TI  - Medical screening and medical-psychological assessment as prerequisites for
      regranting of licenses: summary of recommendations.

PMID- 9010552
TI  - Recidivism among drunken and drugged drivers in Norway.
AB  - The prevalence of re-arrest among drunken drivers in relation to different blood
      alcohol concentrations (BAC) at the time of the offences was studied. Between 38
      and 50% of arrested drunk drivers were re-arrested for similar offences. The
      frequency of re-arrests was, however, reduced during 1992 compared with a986, but
      only significantly for those with a low BAC interval (60-90 mg/d). We conclude
      that drivers with high re-arrest rates have a careless attitude to the Road
      Traffic Act and require a different treatment and follow-up programme.

PMID- 9010553
TI  - Laboratory markers of alcohol abuse.
AB  - A number of routine laboratory markers provide objective information about
      alcohol use and abuse. The usefulness of these markers is discussed. One such
      marker recently developed is serum carbohydrate-deficient transferrin (CDT),
      which has a greater overall marker potential than other existing tests. The use
      of CDT in combination with some of the other markers is likely to enhance the
      detection of alcohol abuse or heavy consumption.

PMID- 9010554
TI  - Evaluation of alcohol consumption level in drivers when regranting licences after
      driving while intoxicated in France.
AB  - Biological markers form an important part of the decision-making process for
      regranting of driving licences in France. A major criterion in this respect is
      the need to distinguish between acute alcohol use and chronic abuse by
      applicants. Current markers reflect more hepatic damage than alcohol consumption
      and this stresses the need for more reliable markers.

PMID- 9010555
TI  - New ways to use biochemical indicators of alcohol abuse to regrant licences in a
      fairer manner after drunken driving in Germany.
AB  - The failure of medical-psychological examination to provide convincing
      recommendations concerning the regranting of licences in a significant number of
      cases illustrates the need for objective laboratory testing. Experience in
      Germany shows that blood-alcohol concentration alone could lead to misleading
      recommendations, and suggests that laboratory testing is best done on samples
      taken at the time of the offence, rather than subsequently at medical
      psychological investigation.

PMID- 9010556
TI  - Treatment of alcohol dependence: experiences of using biological markers in
      monitoring and prevention of relapse.
AB  - The treatment modalities of alcohol consumption are briefly reviewed with special
      emphasis on brief motivational intervention. The usefulness of laboratory markers
      of alcohol consumption in identifying relapses and as adjuncts to therapy
      programmes is highlighted. The recently developed marker, carbohydrate-deficient
      transferrin, has proven to be a promising test in its use to monitor relapse in
      patients using each patient's cut-off value offers advantages over group cut
      offs.

PMID- 9010557
TI  - The use of serum carbohydrate-deficient transferrin in the assessment of 'high
      risk offenders' in Great Britain.
AB  - The potential role of serum carbohydrate-deficient transferrin (CDT) measurement
      in the assessment of 'High Risk Offenders (HROs)' applications for licence
      reinstatement in Great Britain was examined. Serum CDT determination would have
      provided useful confirmation of licence decisions in 70% of HROs assessed, would
      have resulted in a change in the licence decision in 8%, and most likely would
      have confounded the licence decisions made in the remaining 22%. Estimation of
      serum CDT could provide useful information to assist in decisions regarding
      licence reinstatement in selected HROs.

PMID- 9010558
TI  - Nasal response to allergen challenge in patients with immediate asthmatic
      reaction.
AB  - Ten patients with bronchial asthma and allergy to house-dust mite (HDM) and ten
      normal, nonatopic control subjects underwent a bronchial challenge with flour.
      Before and 24 hr after the allergen provocation with flour, the levels of
      eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were determined in
      the serum and nasal lavage fluid. All allergics showed an isolated immediate
      asthmatic reaction (IAR). After the flour challenge only in asthmatic patients
      the increase was detected in the mean values of: 1) eosinophils (mean value
      before 16.7 x 103/mm3; mean after: 10 min 132.9 x 103/ml; 3 hr 183.6 x 103/mm3;
      24 hr 110.6 x 103/mm3, p < 0.05), 2) basophils (mean before 1.2 x 103/mm3; mean
      after: 10 min 5.3 x 103/ml; 3 hr s 14.1 x 103/mm3 24 hr was 18.3 x 103/mm3, p <
      0.05), 3) neutrophils (mean before 9.2 x 103/mm3; mean after 24 h 18.2 x 103/mm3,
      p < 0.05) in the nasal lavage fluid. In contrast to a group of normal subjects,
      asthmatics were found to have higher postchallenge levels of ECP and MPO in the
      nasal secretions as compared with the prechallenge levels (ECP-mean 3.85 ug/l
      compared with 32.17 ug/l, p < 0.05; MPO-mean 120-02 ug/l compared with 1313.2
      ug/l, p < 0.05). The authors did not find any significant difference between pre-
      and postchallenge levels of ECP and MPO in the serum of asthmatics and controls.
      The higher levels of MPO as well as higher count of neutrophils observed in
      asthmatic patients 24 hr after allergen challenge support the neutrophil
      involvement in the allergic inflammation. Our results indicate that both
      neutrophils and eosinophils take part in allergic reaction in the mucosa.

PMID- 9010559
TI  - Serum levels of eosinophil cationic protein and eosinophil protein x in pollen
      atopic patients with stable asthma and its relation with bronchial
      hyperresponsiveness.
AB  - Eosinophils are important effector cells in allergic inflammation described in
      allergic rhinitis (AR) and allergic bronchial asthma (BA). During the pollen
      season serum levels of eosinophil cationic protein (ECP) and eosinophil X
      protein/eosinophil-derived neurotoxin (EPX/EDN) are increased in BA. The aim of
      the present study was to evaluate the serum levels of ECP and EPC in pollen
      atopic patients with AR and BA during the winter. 92 patients were studied. They
      were divided into three groups: I 29 patients with AR, II 51 patients with BA and
      III 12 healthy subjects. Allergic rhinitis and bronchial asthma were diagnosed by
      routine clinical tests: clinical history, skin tests, total IgE and specific IgE.
      In addition ECP and EPX were determined in serum. All patients were asymptomatic,
      stable and without medical treatment. Methacholine challenge test (MCT) was
      performed in all patients. MCT were positive in 4 patients of group I and 45
      patients of group II. ECP levels (ug/l) were: 21 (I), 24 (II) and 7 (III). EPX
      levels (ug/l) were 35 (I), 45 (II) and 21 (III). Statistical differences (p <
      0.01) were observed both in ECP and EPX levels in patients with MCT positive in
      relation to patients with MCT negative, and in allergic patients (I and II) in
      comparison with the healthy subjects (III) (p < 0.01). ECP and EPX serum levels
      are increased in patients with a positive MCT in the winter, out of the pollen
      season, when patients are asymptomatic, stable and without treatment. This fact
      suggests that eosinophils play an important role in the pathogenesis of bronchial
      asthma.

PMID- 9010560
TI  - Evaluation of exposure to mite allergens; flotation, ELISA and Acarex comparative
      study.
AB  - House dust mites (HDM) are a major cause of allergic sensitization and airway
      disease. Technological advances in assays permit the measurement of major mite
      allergens in house dust samples more accurately. We compared the results of
      different methods in the assessment of exposure to domestic mites in sensitized
      patients. Three methods were used for mite assays on house dust samples: Mites
      were evaluated by microscope after flotation technique; major mite allergens. Der
      p l and Der f l, were determined by ELISA; the Acarex-Test was performed for the
      determination of guanine content. There was no significant difference between
      flotation and ELISA in the assessment of mite allergens. However, Acarex-Test was
      different from the other methods tested. being higher in skin test positive
      patients. We found a significant correlation between Der p l levels and mite
      specific immunoglobulin E determined by ELISA and CAP RAST respectively. Our
      findings show that mite determination by flotation method could be reinforced
      where the advanced methods are not available. Although the mite allergen levels
      measured in this study with various methods were not always in close association
      with house dust mite sensitization, the importance of mite-avoidance measure to
      house dust mites evaluated by skin tests and RAST should not be underestimated.

PMID- 9010561
TI  - Preseasonal specific immunotherapy with modified phleum pratense allergenic
      extracts: tolerability and effects.
AB  - The preparation of chemically modified allergens, with a reduced IgE binding
      capacity (responsible for side effects with traditional immunotherapy) but with
      the same or greater immunogenic activity, is one of the paths followed to obtain
      better results with specific immunotherapy (IT). The aim of the study was to
      evaluate the tolerability and effects of extracts of Phleum pratense, modified
      with glutaraldehyde and absorbed on aluminium hydroxide, in controlling the
      seasonal symptomatology induced by grass pollen in a group of 10 monosensitized
      patients, compared to a group of 10 similar patients not treated with specific IT
      but with drugs alone. The monitoring parameters were: 1) Clinical: a)
      symptomatology after specific conjuctival provocation test (pre and post
      seasonal) and during the natural exposure to the allergen b) drug consumption. 2)
      Immunological (peripheral blood eosinophils, total and specific IgE, total
      specific IgG). 3) Cytological, before, during and after the pollen season.
      CONCLUSIONS: in subjects treated with specific IT a) both the overall
      symptomatology and the drug consumption resulted significantly reduced compared
      to the controls (p = 0.045); b) the phlogistic infiltrate showed a tendency to
      decrease during the pollen season; c) the peripheral blood eosinophils, total and
      specific IgE and IgG did not show any significant variation compared to the
      controls; d) no systemic reactions occurred and there were only two slight local
      reactions.

PMID- 9010562
TI  - Monitoring of specific IgG4 antibodies in respiratory allergy due to the pollen
      of Parietaria judaica. Evidence for a protective role.
AB  - Two groups of 20 patients having an allergic rhinitis due to the pollen of
      Parietaria judaica were studied, one received a treatment of specific
      hyposensitization, the other one a placebo. All of them were monosensitized. The
      study was carried out using double blind methodology and was conducted for one
      year. Each case was assessed by clinical tests: case history, skin tests, score
      symptoms, drug consumption, nasal provocation test and by in vitro tests (FAST
      technique): total and specific IgGE, specific IgG4. The clinical tests revealed a
      statistically significant improvement in the treated group as compared to those
      receiving the placebo. We found a statistically significant regular and important
      increase of specific IgG4 values in the treated group. In this case, the specific
      IgG4 antibodies most likely play a protective role and act as blocking
      antibodies.

PMID- 9010563
TI  - Historical background of aeropalynology in the Canary Islands.
AB  - This paper forms part of a Doctorate Thesis, currently being completed at the
      Allergy and Immunology Section of the Ntra. Sra. de la Candelaria Hospital,
      Tenerife, regarding the Epidemiology of pollens We would like to illustrate that
      this island and its provinces are similar to a miniature continent, where pollens
      from the most important allergenic families present in the National Territory of
      the Iberian Peninsula can be found. We have a very high incidence of patients
      allergic to grass pollens (gramineas), Mugwort (Artemisia), Pellitory
      (Parietaria) and plantain (Plantago) pollens, with respect to the number of
      inhabitants and allergic subjects living on our island. In a further paper, we
      shall expose the graphs corresponding to an Aerobiological Study during the last
      five years, where we obtained more than 100 gr of pollen per m3 of air.

PMID- 9010564
TI  - The fibrinoids of the human placenta: origin, composition and functional
      relevance.
AB  - Placental fibrinoids are extracellularly deposited materials which are
      histologically glossy and acid staining, and can be found in every normal and
      pathological placenta at all stages of pregnancy. The amount of fibrinoid is, in
      general, independent of pregnancy outcome and fetal wellbeing. According to new
      findings, the classical histological term "fibrinoid" covers two distinctive
      extracellular matrices which differ as regards structure, composition and
      function. Fibrin-type fibrinoid is mostly composed of fibrin together with other
      molecules derived from blood clotting or degenerative processes. It is mainly a
      maternal blood-clot product which is used (a) to adapt the intervillous space to
      optimized flow conditions and (b) to control growth of the villous trees by
      encasing new villous branches which caused intervillous stasis or turbulence of
      maternal blood. Moreover, fibrin-type fibrinoid replaces degenerative
      syncytiotrophoblast at the maternofetal exchange surfaces, thus acting as a kind
      of substitute barrier. Matrix-type fibrinoid is a secretory product of invasive
      extravillous trophoblast cells. It shares some similarities with basement
      membranes, however, it is secreted in an apolar fashion, embedding the secreting
      cells. Like basement membranes, it contains laminins, collagen IV, and heparan
      sulfate. In addition, oncofetal fibronectins, vitronectin, and i-glycosylated
      molecules but no collagens I, III, and VII can be found. Matrix-type fibrinoid is
      thought to regulate trophoblast invasion by specific interactions with cell
      surface integrins. As a kind of "glue", it anchors the placenta to the uterine
      wall and seems to play an important role in materno-fetal immune interactions at
      this particular site. Both types of fibrinoid are usually co-localized, thus
      indicating close morphogenetic and functional interrelations.

PMID- 9010565
TI  - Development of the parotid gland and its closer neighboring structures in human
      embryos and fetuses of 19-67 mm CRL.
AB  - The fetal development of the human parotid gland was studied by means of serial
      sections of human embryos and fetuses ranging from 19 mm to 67 mm CRL. Analysis
      of computer assisted 3-dimensional reconstructions and anatomical drawings leads
      to the following observations: 1. The parotid gland anlage is found at the most
      lateral and cranial point of the sulcus buccalis. 2. The location of the orifice
      of the parotid duct is dependent upon the developmental processes of the fetal
      skeleton. 3. The anlagen of anatomical structures dominating the parotid bed in
      the adult are found prior to the enlargement of the parotid gland. 4. The surface
      of the parotid gland shows impressions of the surrounding structures. 5. There is
      no evidence that the parotid gland is subdivided into two lobes by the facial
      nerve.

PMID- 9010566
TI  - Development of the submandibular gland and its closer neighboring structures in
      human embryos and fetuses of 19-67 mm CRL.
AB  - The fetal development and arrangement of the human submandibular gland was
      studied by means of serial sections of human embryos and fetuses ranging from 19
      mm to 67 mm CRL. Computer assisted 3-dimensional reconstruction leads to the
      following observations: 1. The orifice of the submandibular duct is located in
      the medial paralingual sulcus. 2. There is evidence that the extension and
      location of WHARTON's duct is influenced by the surrounding structures. 3. The
      surface of the submandibular gland primordium shows impressions of the
      neighboring structures. 4. The glandular tissue is encapsulated in condensed
      mesenchyme.

PMID- 9010567
TI  - The structure of sensory nerve endings in the knee joint capsule of the dog.
AB  - The ultrastructure and distribution patterns of sensory nerve endings in the
      dorsal knee joint capsules of the beagle dog (Canis familiaris) have been
      investigated using light and electron microscopy. Each dorsal knee joint capsule
      was divided into four quadrants, cut into small pieces and then processed for
      electron microscopy. Free nerve endings and corpuscular nerve endings (Ruffini
      and lamellated corpuscles) were found. They were most frequently observed in the
      medial-proximal quadrant of the dorsal joint capsule. All nerve endings were
      found to be situated within or adjacent to the fibrous layer of the capsule. No
      nerve endings were found within the synovial layer. Free nerve endings were
      usually situated at the border between the fibrous layer and the synovial layer
      near blood vessels. Their associated afferent axon was myelinated (1.5-2.5
      microns in diameter) or non-myelinated (0.3-1.5 microns in diameter). Ruffini
      corpuscles were found in the fibrous layer and within the dorsal ligamentous
      apparatus. Each Ruffini corpuscle was surrounded by a multilayered perineural
      capsule which was usually incompletely developed. The perineural capsule is the
      continuation of the perineurium of the afferent axon and gives a cylindrical form
      to the corpuscles. Ruffini corpuscles were present as single, cylindrical
      structures (small corpuscles) or as aggregates of these cylinders (large
      corpuscles). Both varieties consist of terminal nerve endings surrounded by
      collagen fibres which pass through the opened ends of the cylinders. The diameter
      and length of the small Ruffini corpuscles were 80 microns and 400 microns, as
      compared to 200 microns and 800 microns for the large aggregated forms. The
      supplying afferent axons of both types were 4-5 microns in diameter. Two types of
      small lamellated corpuscles could be observed in the fibrous layer: very small
      corpuscles, 55 microns long, 25 microns wide and medium corpuscles, 100 microns
      long, 40 microns wide. Each consists of an inner core of terminal Schwann cells,
      a nerve terminal and a perineural capsule. Some lamellated corpuscles had two
      inner cores and two nerve terminals. The diameter of the afferent axon was
      approximately 6 microns. Vater-Pacini corpuscles were not found in the dorsal
      knee joint capsule of the dog.

PMID- 9010568
TI  - Observations on the chorioallantoic placenta of the Indian flying fox, Pteropus
      giganteus giganteus.
AB  - The present study was undertaken to resolve (1) whether the interhaemal membrane
      of Pteropus giganteus at term is endotheliochorial or haemochorial and (2) how
      the trophoblast is layered. Females carrying late limb bud stage (CRL 12.95 mm)
      and advanced fetus (CRL 26.95 mm) were collected at Nagpur, India. The placenta
      in late limb bud stage was examined by light microscopy and that of advanced
      pregnancy by both light and electron microscopy. Our observations reveal that the
      chorioallantoic placenta at late limb bud stage is horse-shoe shaped and
      endotheliodichorial while that of advanced pregnancy is mesometrial,
      labyrinthine, and discoidal and shows a tendency toward becoming haemochorial.
      The junctional zone contained multinucleate giant cells. Detached endothelial
      cells were observed in the maternal capillary lumen during the advanced stage.
      Under light microscope a thick homogeneous layer was noticed deeper to the
      endothelial cells and in the regions devoid of such cells. A PAS-positive, highly
      reticulate and discontinuous interstitial membrane was noticed embedded in the
      thickness of the homogeneous layer. The ultrastructure of the interhaemal
      membrane of the chorioallantoic placenta in advanced pregnancy shows a tendency
      from endotheliodichorial to haemodichorial condition. The Pteropus interhaemal
      membrane is compared with that of bats of other families. The earlier conclusion
      that the maternal endothelium is typically different for primitive and extant
      families is denied on the basis of comparative ultrastructure.

PMID- 9010569
TI  - The distributive pattern, form and function seen in microvascular cast specimens
      of filiform papillae on the anterodorsal surface of the adult rat tongue.
AB  - The purpose of the present study was to examine in detail the distributive
      pattern, form and function of small conical papillae (SCP) and of filiform
      papillae (FIP) in the anterodorsal part of the adult rat fore-tongue in a
      microvascular cast specimen (MVCS), with the scanning electron microscope (SEM),
      and to elucidate the close relationship between the morphological characteristics
      and the function of the tongue. From the results obtained in this study, SCP in
      the anterior part were subdivided into three types: SCP type I, II and III
      according to the shape, size, distributive pattern and form taken from the two
      peripheral sides as for as the median sulcus (MS) in the central portion. The
      results we obtained suggested that the primary role of SCP types I and II at the
      apex may be mainly that of touch and attachment to the food and water, while SCP
      types II and III in the anterior part function efficiently by taking the food and
      water from both peripheral sides to the MS or central portion, and finally
      transporting it into the oral cavity and supporting the mastication system.

PMID- 9010570
TI  - A study of the three-dimensional organization of the human diaphragmatic
      lymphatic lacunae and lymphatic drainage units.
AB  - The peritoneal stomata, lymphatic drainage units and subperitoneal terminal
      lymphatics, called lymphatic lacunae, form a specialized drainage system in the
      diaphragm, by which absorption of fluid in bulk, particles and cells is carried
      out in the peritoneal cavity. The aim of this study is to elucidate the three
      dimensional organization and function of the subperitoneal lymphatic lacunae and
      lymphatic drainage units by using lymphatic casts in the scanning electron
      microscope (SEM), ODO (OsO4-DMSO-OsO4) freeze fracture, conventional SEM and the
      transmission electron microscope (TEM). The subperitoneal lymphatic lacuna is
      unique for its large size and its multiple morphology and can be recognized by
      its broad, flattened enlargement and the blind-ends of lymphatic vessels, from
      which extend numerous main lymphatic vessels and side branches. These lymphatic
      vessels communicate with each other and form a rich lymphatic plexus under the
      diaphragmatic peritoneum. Two layers of lymphatic networks, i.e. the
      subperitoneal plexus and the deeper plexus are found in the muscular portion.
      Only one layer is present in the tendinous portion of the human diaphragm. The
      lymphatic plexus is denser in the tendinous portion than that in the muscular
      portion. The lymphatic lacunae occur exclusively in the muscular portion of the
      human diaphragm. The lumina of lymphatic lacunae are separated from the
      peritoneal cavity by a barrier consisting of cuboidal mesothelial cells,
      endothelial cells of the lymphatic lacunae and intervening connective tissue
      forming a lymphatic drainage unit. All these three components of the lymphatic
      drainage unit abut upon each other, but are not linked by specialized junctions.
      The cuboidal mesothelial cells frequently extend valve-like cytoplasmic processes
      that bridge the subperitoneal channel and make give it a tortuous course. The
      fibrous layer of the connective tissue is arranged in fiber bundles and gives a
      three-dimensional network forming the floor of the peritoneal stomata and the
      roof of the lymphatic lacunae. Via the fibrous network, the cuboidal mesothelial
      cells and the endothelial cells of the lacunae come into close contact with each
      other and form short subperitoneal channels which connect the peritoneal cavity
      with the subperitoneal lymphatic lacunae. The lymphatic drainage units may
      regulate the material absorption of the peritoneal stomata from the peritoneal
      cavity. It is suggested that the peritoneal stomata together with the
      subperitoneal channels, lymphatic drainage units and lymphatic lacunae comprise
      an important diaphragmatic lymphatic drainage system which plays an important
      role in the absorption of materials from the peritoneal cavity.

PMID- 9010571
TI  - Growth, morphology, morphometry and keratin patterns of bovine corneal epithelial
      cells cultured in vitro.
AB  - In this study, the effects of different culture systems on bovine corneal
      epithelial cells were analysed in order to better understand the influence of
      bovine keratocytes on epithelial cells. Growth, morphological, morphometrical
      analyses of cells and keratin patterns were evaluated. The aim was to improve the
      culture technique in order to obtain a good in vitro proliferation of these cells
      for their employment in clinical and toxicological situations. The bovine corneal
      epithelial cells were cultured under different conditions: on keratocyte or 3T3
      J2 fibroblast feeder layers, with media conditioned either by the two feeder
      layers or with a basal medium. The epithelial cells cultured on a keratocyte
      feeder layer as compared to those grown under the other conditions, proved to
      have a higher growth rate as well as to be smaller in the cytoplasmic and nuclear
      area; moreover, after 21 days of culture they expressed 64-kDa keratin, designed
      as a marker for corneal epithelial cell differentiation. To sum up, the
      keratocyte feeder layer is the most effective for stimulating the growth and
      differentiation of corneal epithelial cells, resembling the in vivo situation. It
      might also be successfully employed for clinical and toxicological purposes.

PMID- 9010572
TI  - Anatomy of the circle of Willis in three cases of human fetal synophthalmic
      holoprosencephaly.
AB  - In three human fetuses with synophthalmic holoprosencephaly (8, 14, 23 weeks post
      conceptionem) the circle of Willis was studied using serial histological sections
      and computer aided three dimensional reconstruction methods. This structure was
      abnormal in all cases. In two cases the anterior communicating arteries were
      absent. In all cases the anterior cerebral arteries could not be found. One case
      showed an incomplete circle with no posterior communicating artery. The results
      indicate that the malformation of the circle of Willis reflects the malformation
      of the brain.

PMID- 9010573
TI  - New classification of low-grade lymphoma.
AB  - The problem of morphologic classification of the indolent non-Hodgkin's lymphomas
      has been addressed by the National Cancer Institute Working Formulation, the
      International Lymphoma Study Group, and other groups. The criteria for
      classification have expanded to include biologic and laboratory parameters.
      Clinical aspects are important, because diagnostic categories that obscure
      discrete entities, such as mucosa-associated B-cell lymphoma could adversely
      affect therapy. This and other indolent non-Hodgkin's lymphomas and mantle-cell
      lymphoma, which has been provisionally included among them, are reviewed.
      Variations in nomenclature, immunohistochemical and molecular characteristics,
      and whenever possible, prognosis and clinical outcome are described. The need for
      further correlation with clinical outcome of these entities is noted.

PMID- 9010574
TI  - Classification and clinical course of low-grade non-Hodgkin's lymphomas with
      overview of therapy.
AB  - Low-grade non-Hodgkin's lymphoma (NHL) presents a formidable treatment challenge
      to oncologists. This review evaluates the various methods of disease and patient
      management. The natural history of various subtypes of low-grade NHL and the
      classification according to the National Cancer Institute Working Formulation are
      discussed in this review. Additionally, the various therapies in use;
      radiotherapy alone and combined with chemotherapy, chemotherapy with single
      alkylating agents such as chlorambucil and combination therapies, autologous and
      allogenic bone marrow transplantation, and therapy with purine analogs, such as
      chlorodeoxyadenosine and fludarabine. Patient survival in various studies using
      these treatment modalities are discussed. Treatment options need to be combined
      with the use of prognostic models, such as the International Index for optimal
      care of this difficult-to-treat group of patients.

PMID- 9010575
TI  - Purine analogs in marginal-zone lymphomas.
AB  - In an area of lymphoma classification still being defined, marginal-zone
      lymphomas have distinctive immunohistochemical and cytogenetic features that
      distinguish them from mantle-cell and follicular lymphomas. There are three
      subtypes: the extranodal mucosa-associated lymphoid tissue (MALT) lymphomas, the
      nodal monocytoid B-cell (MBCL) lymphomas, and the splenic marginal-zone
      lymphomas. The MALT lymphomas represent the neoplastic counterpart of the gut
      associated lymphoid tissue, which extends from the jejunum to the rectum. They
      arise in sites usually containing no lymphoid tissue, such as the stomach,
      thyroid, and salivary gland. Gastric MALT lymphomas, the most common, are
      associated with Helicobacter pylori. The MBCL lymphomas closely resemble MALT
      lymphomas and unlike other non-Hodgkin's lymphomas are commonly composite.
      Therapy for these lymphomas may include radiation therapy or surgery when disease
      is of limited extent. However, gastrectomy for gastric MALT lymphomas is not in
      favor because of the efficacy of antibiotic regimens that can eliminate H. pylori
      infection. Splenectomy may be indicated for splenic lymphomas. Purine analogs are
      promising therapeutic agents because they are specific for lymphoid cells. Also,
      they may prove useful in indolent cancers such as these, because of their
      activity against dividing and resting cells. Purine analogs may be considered as
      second-line therapy after alkylating agents for these lymphomas.

PMID- 9010576
TI  - Purine analogs in chronic lymphocytic leukemia and Waldenstrom's
      macroglobulinemia.
AB  - The observation of lymphopenia in children deficient in adenosine deaminase (ADA)
      led to exploration of an inhibitor of the enzyme in lymphoid malignancies; thus
      deoxycoformycin was the first purine nucleotide used in human trials. Fludarabine
      and 2-chlorodeoxyadenosine (2-CdA), agents resistant to deamination by ADA, have
      been utilized in the past decade. All of these drugs act as competitors for
      deoxyadenosine triphosphate at the A sites of the elongating DNA strand,
      terminating DNA synthesis. However, their remarkable efficacy in indolent
      lymphoid malignancies is not well explained by this mechanism of action. The
      induction of apoptosis and resultant cytotoxicity may be important in their
      activity. As a single agent, fludarabine has been associated with overall
      remission rates as high as 55% in previously treated patients and 79% in
      previously untreated patients. With this agent, a dosage regimen of 25-30 mg/m2
      daily over 5 days seems to be the most effective to date. Fludarabine has shown
      more favorable remission rates than the traditional salvage regimens
      incorporating anthracyclines and alkylating agents. Regimens combining
      fludarabine with mitoxantrone and with doxorubicin have shown minimal therapeutic
      advantage in CLL, while combination with cyclophosphamide appears promising.
      Remission rates with deoxycoformycin have been lower than with fludarabine, but
      studies have been small in patient numbers. The agent 2-CdA, first successful in
      hairy-cell leukemia, has shown overall response rates in chronic lymphocytic
      leukemia similar to those seen with fludarabine. Whether or not cross-resistance
      occurs among the purine analogs has not been fully determined, but occasional
      patients with disease refractory to fludarabine have responded to 2-CdA.
      Cumulative myelosuppression and immunosuppression may be experienced however. In
      the B-cell neoplastic entity, Waldenstrom's macroglobulinemia, fludarabine
      therapy in patients previously treated with alkylating agents and/or steroids
      produced a 36% response rate. Only two previously untreated patients received
      fludarabine, and both responded. A similar response rate of 40% was seen when 2
      CdA was administered to previously treated patients. This response rate increased
      to 85% in a study of 26 previously untreated patients, making this one of the
      most effective drugs yet investigated in this condition.

PMID- 9010577
TI  - Mantle-cell lymphoma: classification and therapeutic implications.
AB  - Mantle-cell lymphomas have been recognized in the new Revised European-American
      Lymphoma Classification as a peripheral B-cell neoplasm that has a distinct
      morphologic, immunologic, and genetic phenotype. Mantle-cell lymphomas have been
      subtyped into four categories, termed 'mantle zone', 'nodular', 'diffuse', or
      'blastoid'. The incidence of the 'mantle-zone' pattern remains controversial. The
      fact that patients with the nodular, diffuse, or blastoid subtypes of mantle-cell
      lymphoma have a high proliferative rate resulting from overexpression of the
      cyclin D1 and a very short median survival demonstrates conclusively that these
      patients should be categorized as having an aggressive lymphoma. Most authorities
      believe that the 'mantle zone' variant pursues a more benign clinical course than
      the other subtypes. Trials of the new purine analogs are of great interest in
      these mantle-zone lymphoma patients.

PMID- 9010578
TI  - Purine nucleoside therapy of low-grade follicular lymphoma.
AB  - Low-grade follicular lymphomas, follicular small cleaved and follicular mixed,
      generally follow an indolent but progressive course. Although available therapies
      induce responses, continuous relapse occurs. In investigating potential
      therapeutic regimens, researchers have sought regimens that will result in a
      postchemotherapy survival plateau rather than a pattern of continuous relapse.
      The newer, purine analogs, 2'-deoxycoformycin, fludarabine, and 2
      chlorodeoxyadenosine have shown activity in the low-grade B-cell lymphomas,
      especially with the follicular histologic subtype. Response rates in studies of
      previously untreated patients approach 100%. The newer purine analogs are
      emerging as an important treatment approach for indolent B-cell lymphomas, but
      the impact on survival remains to be assessed.

PMID- 9010579
TI  - Acute inhalation toxicity testing: considerations of technical and regulatory
      aspects.
AB  - The EU regulatory statute for the acute hazard identification of chemicals
      requires selection of the two most appropriate routes of administration. Testing
      employing the oral route is mandatory, whereas selection of the dermal or
      inhalation route requires expert judgement, i.e. considerations of structural
      alerts with regard to the inherent acute inhalation toxicity as well as the
      likelihood of dermal and inhalation exposure, respectively. Currently, testing of
      chemicals requires acute inhalation exposure of 4-h and 1-h durations according
      the EU classification and labelling and UN Transport Guidelines, respectively.
      The analysis made revealed that 1-h exposures appear to add little knowledge in
      addition to existing 4-h LC50 values and a default value of 4 should be used for
      conversion of 4-h to 1-h LC50 values, independently of the physical state of the
      chemical. Therefore, also the unit of concentration of exposure atmospheres
      should be independent of nominal features of the test substance. Hence, the
      preferred dose metric is mass (mg/liter air) rather than volume (ppm). Taking
      into account the overall variability of acute toxicity data the recommendations
      given are classification into the following groups of 4-h LC50 values: < or =
      0.05, > 0.05-0.2, > 0.2-1, > 1-5 and > 5.0 mg/l. No distinction should be made
      concerning vapours and aerosols with regard to units and conversion factors from
      4-h to 1-h LC50 values and the default factor of 4 appears to be most suitable.
      Further differentiation of classification is not indicated due to technical
      variability of acute inhalation testing and resolution of the acute bioassay.

PMID- 9010580
TI  - Long-term cadmium exposure induces anemia in rats through hypoinduction of
      erythropoietin in the kidneys.
AB  - Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general
      environment of today. The characteristic clinical manifestations of chronic Cd
      intoxication include renal proximal tubular dysfunction, general osteomalacia
      with severe pains, and anemia. We have recently reported that the serum level of
      erythropoietin (EPO) remained low despite the severe anemia in patients with Itai
      itai disease, the most severe form of chronic Cd intoxication. In order to prove
      that the anemia observed in chronic Cd intoxication arises from low production of
      EPO in the kidneys following the renal injury, we administered Cd to rats for a
      long period and performed the analysis of EPO mRNA inducibility in the kidneys.
      The rats administered Cd for 6 and 9 months showed anemia with low levels of
      plasma EPO as well as biochemical and histological renal tubular damage, and also
      hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd
      intoxication causes anemia by disturbing the EPO-production capacity of renal
      cells.

PMID- 9010581
TI  - Protective effect of vitamin E on chromium (VI)-induced cytotoxicity and lipid
      peroxidation in primary cultures of rat hepatocytes.
AB  - Pretreatment of primary cultures of rat hepatocytes with alpha-tocopherol
      succinate (vitamin E) for 20 h prior to exposure to K2Cr2O7 resulted in a marked
      decrease of chromium (VI)-induced cytotoxicity, as evaluated by the leakage of
      lactate dehydrogenase, without affecting cellular uptake and the subcellular
      distribution of chromium. The levels of chromium (VI)-induced lipid peroxidation,
      as monitored by malondialdehyde formation, were also inhibited by pretreatment
      with the vitamin. Pretreatment with vitamin E normalized the levels of
      nonenzymatic antioxidants such as glutathione and vitamin C suppressed by
      dichromate, and caused a distinct accumulation of vitamin E in hepatocytes.
      However, vitamin E pretreatment did not affect the activities of enzymatic
      antioxidants including glutathione reductase, superoxide dismutase, and catalase
      suppressed by dichromate. These results indicate that the protective effect of
      vitamin E against chromium (VI)-induced cytotoxicity as well as lipid
      peroxidation, may be associated more with the level of nonenzymatic antioxidants
      than the activity of enzymatic antioxidants.

PMID- 9010582
TI  - Contribution to the mechanism of chromate nephrotoxicity in developing rats: EPR
      investigations.
AB  - The effect of 2 mg and 1 mg Na2Cr2O7 (Cr)/100 g body wt. on renal function was
      investigated in 10- and 55-day-old rats, respectively. These doses were followed
      by equal Cr concentrations in the renal tissue of both age groups. Confirming
      previous data we found lower nephrotoxicity in young than in adult rats. The
      concentration of glutathione (GSH) and the activity of glutathione reductase
      (GSSG reductase) in renal tissue of adult rats were diminished by buthionine
      sulfoximine (BSO) and lomustine (CCNU) administration, respectively. In these
      animals Cr nephrotoxicity was decreased significantly. Lower nephrotoxicity was
      accompanied by slower disappearance of Cr(VI) from renal tissue homogenate in
      vitro. The time course of Cr(VI) reduction demonstrated by the signal intensity
      of Cr(V), as recorded by electron spin resonance (EPR) spectroscopy in the
      supernatant of renal tissue homogenate, enabled us to follow the reduction of
      Cr(VI) to Cr(III) via Cr(V). Maximally reached Cr(V) concentrations lowest in
      young rats, did not differ significantly in adult control and BSO and BSO + CCNU
      treated rats. Further reduction of Cr(V) to Cr(III) which appeared most rapidly
      in adult rats, was delayed by pretreatment with BSO and CCNU. From our results we
      concluded that (1) reduction of Cr(VI) was more related to the concentration of
      GSH than to the activity of GSSG reductase, (2) the formation of Cr-GSH-complexes
      with GSH oxidation seemed to be the first step of Cr(VI) metabolism, and (3) the
      stabilization of reactive Cr(V) by GSH seemed to be decisive for the preventive
      effect of BSO and CCNU as well as for age differences in chromate nephrotoxicity.

PMID- 9010583
TI  - Mechanisms of selenium methylation and toxicity in mice treated with
      selenocystine.
AB  - Mechanisms of selenium methylation and toxicity were investigated in the liver of
      ICR male mice treated with selenocystine. To elucidate the selenium methylation
      mechanism, animals received a single oral administration of selenocystine (Se
      Cys; 5, 10, 20, 30, 40, or 50 mg/kg). In the liver, both accumulation of total
      selenium and production of trimethylselenonium (TMSe) as the end-product of
      methylation were increased by the dose of Se-Cys. A negative correlation was
      found between production of TMSe and level of S-adenosylmethionine (SAM) as
      methyl donor. The relationship between Se-Cys toxicity and selenium methylation
      was determined by giving mice repeated oral administration of Se-Cys (10 or 20
      mg/kg) for 10 days. The animals exposed only to the high dose showed a
      significant rise of aspartate aminotransferase (AST) and alanine aminotransferase
      (ALT) activities in plasma. Urinary total selenium increased with Se-Cys dose.
      TMSe content in urine represented 85% of total selenium at the low dose and 25%
      at the high dose. The potential of Se-methylation and activity of methionine
      adenosyltransferase, the enzyme responsible for SAM synthesis, and the level of
      SAM in the liver were determined. The high dose resulted in inactivation of Se
      methylation and decrease in SAM level due to the inhibition of methionine
      adenosyltransferase activity. To learn whether hepatic toxicity is induced by
      depressing selenium methylation ability, mice were injected intraperitoneally
      with periodate-oxidized adenosine (100 mumol/kg), a known potent inhibitor of the
      SAM-dependent methyltransferase, at 30 min before oral treatment of Se-Cys (10,
      20, of 50 mg/kg). Liver toxicity induced by selenocystine was enhanced by
      inhibition of selenium methylation. These results suggest that TMSe was produced
      by SAM-dependent methyltransferases, which are identical with those involved in
      the methylation of inorganic selenium compounds such as selenite, in the liver of
      mice orally administered Se-Cys. Depression of selenium methylation ability
      resulting from inactivation of methionine adenosyltransferase and Se-methylation
      via enzymic reaction was also found in mice following repeated oral
      administration of a toxic dose of Se-Cys. The excess selenides accumulating
      during the depression of selenium methylation ability may be involved in the
      liver toxicity caused by Se-Cys.

PMID- 9010584
TI  - Identification and metabolism of selenocysteine-glutathione selenenyl sulfide
      (CySeSG) in small intestine of mice orally exposed to selenocystine.
AB  - This investigation was carried out to elucidate the chemical form of selenium
      containing metabolite in small intestine of ICR male mice orally administered
      selenocystine (CySeSeCy). The metabolite in intestinal cytosol of mice treated
      with CySeSeCy (50 mg/kg) was identified as selenocysteine-glutathione selenenyl
      sulfide (CySeSG) by high performance liquid chromatography using a gel filtration
      and reversed phase column. Hydrogen selenide formation was caused as a result of
      the anaerobic reaction between the CySeSG and liver cytosol containing
      selenocysteine beta-lyase, which specifically acts on selenocysteine (CySeH).
      Effects of GSH or glutathione reductase on hydrogen selenide formation from
      CyseSG reacted with the liver cytosol were examined. The CySeSG was
      nonenzymatically reduced to CySeH by excess GSH in the liver cytosol. It was also
      recognized that CySeSG was enzymatically reduced to CySeH by glutathione
      reductase in the presence of NADPH. These results indicate that the chemical form
      of this metabolite is CySeSG, which has a molecular weight of 473, the CySeSG is
      then reduced by excess GSH and/or glutathione reductase yielding CySeH, which is
      decomposed by selenocysteine beta-lyase to hydrogen selenide. CySeSG may be a
      stable precursor of hydrogen selenide in animals.

PMID- 9010585
TI  - The role of CYP2E1 and 2B1 in metabolic activation of benzene derivatives.
AB  - CYP2B1 and 2E1 oxidized toluene, aniline and monochlorobenzene (MCB) to water
      soluble metabolites and to products covalently binding to microsomal proteins
      from male Wistar rats at high efficiency. Oxidation of benzene to covalently
      binding metabolites was catalysed by CYP2B1 and 2E1 more effectively than the
      formation of water-soluble metabolites, especially at low benzene levels. Thus,
      the formation of covalently binding products was inversely related but formation
      of soluble metabolites was proportional to benzene concentration. 1,4
      Benzoquinone was responsible for the majority of covalent binding to microsomal
      proteins, being suppressed by ascorbate; 1,4-semiquinone was not important, since
      alpha-tocopherol did not inhibit the covalent binding and ESR showed its rapid
      decay, if NADPH was available. Specific antibodies and inhibitors confirmed the
      role of CYP2B1 and 2E1 induction. Covalent binding of benzene to DNA was largely
      due to benzene oxide; approximately 50% was due to N-7 guanine adduct. CYP2E1
      oxidizing benzene via phenol to 1,4-hydroquinone appeared to mediate its further
      oxidation to 1,4-benzoquinone, which also occurred spontaneously, but was
      reversed in a reducing environment of microsomes with NADPH. Production of OH
      radicals in microsomes with NADPH was greatly stimulated by HQ and less by BQ,
      especially in CYP2E1 induced microsomes, although the quinones themselves failed
      to produce OH radicals. The quinones could act by simulation of the CYP futile
      cycle. Therefore, CYP2B1 and 2E1 in rats appeared essential for metabolic
      activation of benzene derivatives to potentially genotoxic products; BQ dominated
      the covalent binding of benzene to proteins, whereas DNA adducts were largely due
      to benzene oxide.

PMID- 9010586
TI  - Expression and inducibility of cytochrome P450 proteins in the liver of chick
      embryo.
AB  - The expression and inducibility of cytochrome P450 proteins in the liver of chick
      embryo were investigated using substrate probes and/or immunologically using
      polyclonal antibodies to the mammalian isoforms. Antibodies to CYP1A1 recognised
      a single protein which was inducible by structurally diverse chemicals, including
      aminocompounds, and was parallelled by increases in the O-dealkylations of ethoxy
      and methoxyresorufin and in the bioactivation of Glu-P-1. When probed with
      antibodies to CYP2E1 an immunoreacting protein was revealed which was induced by
      phenobarbital but not acetone; a second protein became apparent following the
      treatment with phenobarbital. The increase in apoprotein levels was accompanied
      by similar increases in p-nitrophenol hydroxylase. Antibodies to CYP2C11
      recognised two immunorelated proteins, of which one was inducible by
      phenobarbital. The same inducer, but not dexamethasone, enhanced the N
      demethylation of erythromycin but antibodies to rat CYP3A1 failed to detect any
      proteins. Finally, lauric acid hydroxylation was not detectable in chick embryo
      and, moreover, no immunoreacting band was visible following probing of microsomes
      with anti-CYP4A1. It is concluded that proteins immunorelated to the mammalian
      CYP1 and CYP2 families are expressed in chick embryo but the regulation of the
      latter family in the embryo by exogenous chemicals differs markedly from that
      established for mammals.

PMID- 9010587
TI  - A convenient method to discriminate between cytochrome P450 enzymes and flavin
      containing monooxygenases in human liver microsomes.
AB  - Liver microsomes are a frequently used probe to investigate the phase I
      metabolism of xenobiotics in vitro. Structures containing nucleophilic hetero
      atoms are possible substrates for cytochrome P450 enzymes (P450) and flavin
      containing monooxygenases (FMO). Both enzymes are located in the endoplasmatic
      reticulum of hepatocytes and both need oxygen and NADPH as cofactors. The common
      method to distinguish between the two enzyme systems is to use the thermal
      inactivation of FMO and to inhibit P450 completely with carbon monoxide, N
      octylamine or N-benzylimidazole. In the literature no indication could be found
      that the heat inactivation of FMO does not affect any of the human P450 enzymes
      or that the overall P450 inhibitors inhibit the different human P450 enzymes
      sufficiently and do not affect the FMO. The effect of N-benzylimidazole and heat
      inactivation was tested on specific activities of seven P450 enzymes in human
      liver microsomes, 1A2, 2A6, 2C9, 2C19, 2D6, 3A4/5, and 2E1, using
      methoxyresorufin O-demethylation, coumarin 7-hydroxylation, (S)-warfarin 4
      hydroxylation, (S)-(+)-mephenytoin 4-hydroxylation, dextrometorphan O
      demethylation, oxidation of denitronifedipine, and chlorzoxazone 6-hydroxylation
      respectively. The sulfoxidation of methimazole (MMI) was used as a specific probe
      for the determination of FMO activity. Methimazole sulfoxidation was compared
      with the well known assay for FMO metabolism, the formation of N,N
      dimethylaniline (DMA) N-oxide, to be confirmed as an exclusively FMO mediated
      reaction. The participation of P450 and FMO in the sulfoxidation of four sulfur
      containing peptides, ametryne; terbutryne, prometryne and methiocarb was
      investigated using human liver microsomes. All four reactions were demonstrated
      to be catalysed predominantly by cytochrome P450.

PMID- 9010588
TI  - Modulation of aflatoxin B1 biotransformation by beta-naphthoflavone in isolated
      rabbit lung cells.
AB  - The cytotoxic and carcinogenic mycotoxin aflatoxin (AF) B1 (AFB1) is
      biotransformed by the cytochrome P450 monooxygenases (CYP) to a number of
      relatively nontoxic metabolites, as well as to the ultimate toxic metabolite,
      AFB1-8,9-epoxide. In a number of tissues and species, AFB1 hydroxylation to the
      relatively nontoxic metabolite, AFM1, is induced by beta-naphthoflavone (BNF)
      treatment. Although the liver is the principle target organ for AFB1 toxicity,
      the mycotoxin is also toxic and carcinogenic to respiratory tissues. To determine
      if BNF treatment alters the extent of pulmonary AFB1 bioactivation by enhancing
      detoxification and thereby decreasing epoxidation, the effects of BNF on
      pulmonary AFB1 metabolism were examined. Rabbit lung cells, isolated by protease
      digestion and centrifugal elutriation, were incubated with [3H]AFB1. In
      nonciliated bronchiolar epithelial (Clara) cell-enriched (45-50%) fractions,
      [3H]AFM1 production (pmol/mg DNA per 2 h) was increased by prior treatment of
      rabbits with BNF (80 mg/kg per day, 3 and 2 days before cell isolation) as
      follows: with 1.0 microM [3H]AFB1; control, 10.6 +/- 2.3; BNF, 30.0 +/- 6.4; with
      0.10 microM [3H]AFB1; control, 9.4 +/- 4.7; BNF, 20.6 +/- 5.9. With 1.0 microM
      [3H]AFB1, prior treatment of animals with BNF abolished formation of
      [3H]aflatoxicol (AFL) but not [3H]AFQ1. The activation (epoxidation) of [3H]AFB1
      was measured indirectly as covalent binding to endogenous DNA. With 1.0 microM
      [3H]AFB1, treatment of rabbits with BNF did not alter DNA binding (pmol/mg DNA
      per 2 h) in the Clara cell-enriched fraction: control, 103 +/- 41; BNF, 114 +/-
      49. However, with 0.10 microM [3H]AFB1, DNA binding in the same fraction was 47%
      lower in cells from BNF treated animals: control, 17.4 +/- 4.2; BNF, 9.3 +/- 3.9.
      Formation of 8,9-dihydro-8,9-dihydroxy-AFB1, and the glutathione conjugate of the
      aflatoxin epoxide (AFB1-GSH) were not detectable at the AFB1 concentration and
      time point studied, in cells from either BNF-treated or control rabbits.
      Incubation of isolated, unseparated lung cells from untreated rabbits with 5.0 to
      50 microM BNF decreased [3H]AFB1-DNA binding in the presence of 0.1 microM
      [3H]AFB1 by 35 to 77%, while lower BNF concentrations did not alter DNA binding.
      In lung cells isolated from BNF treated rabbits, BNF was not detectable (i.e. <
      0.5 microM detection limit). Therefore, the amount of BNF present in isolated
      rabbit lung cells following in vivo treatment with BNF was below that required to
      directly inhibit AFB1-DNA adduct formation. The decrease in AFB1-DNA binding from
      rabbits treated with BNF is apparently due to the selective induction of CYP
      isozymes and related increases in AFM1 formation, and not to direct inhibition of
      epoxidation or enhanced conjugation of AFB1-8,9-epoxide with glutathione.

PMID- 9010589
TI  - Urinary antigens as markers of papillary toxicity. I. Identification and
      characterization of rat kidney papillary antigens with monoclonal antibodies.
AB  - Monoclonal antibodies were prepared in an attempt to develop diagnostic tools for
      the identification of toxic damage to the rat renal papilla. One IgG and five IgM
      monoclonal antibodies, reacting with antigens localized in the papilla were
      obtained. Three of the IgM class and the IgG class monoclonal antibodies were
      found to be specific for antigens localized in collecting ducts, two of them
      staining papillary collecting ducts more intensely than cortical collecting
      ducts. The IgG class antibody, termed Pap X 5C10, recognizes an antigen located
      at high density on the luminal side of papillary collecting duct epithelial cells
      and at lower density in cortical collecting duct cells. One of the IgM class
      monoclonal antibodies reacts with an antigen localized in epithelial cells as
      ascending and descending loops of Henle and of connecting tubules. Another of the
      IgM class monoclonal antibodies reacts with an antigen localized in the
      interstices of the inner medulla. All these monoclonal antibodies react with
      their antigens in native frozen as well as in Bouin-fixed and paraffin-embedded
      tissue slices. Molecular properties of the Pap X 5C10 antigen have been
      investigated by gel permeation chromatography, SDS-PAGE, Western blotting, and
      isoelectric focusing. The results indicate that the antigen in both its tissue
      derived and urinary form is of large (150-200 kDa) molecular size and can be
      separated into two molecular species with isoelectric points of pH 7.2 and 7.3
      respectively. In the urine the antigens recognized by the monoclonal antibodies
      form large complexes with Tamm-Horsfall protein. The antigen-containing complexes
      can be extracted from urine by adsorption to diatomaceous earth and elution with
      SDS-containing buffer. Using sandwich ELISA-type assays it is possible to
      determine the concentration of the antigens. In preliminary experiments we were
      able to show that at least three of the antigens are detected in the urine
      following toxic insults to the kidney. The monoclonal antibodies prepared and the
      tests developed thus may provide direct diagnostic access to the renal papilla
      and allow, for the first time, early detection of papillary damage.

PMID- 9010590
TI  - Selective cytotoxicity associated with in vitro exposure of fresh rat renal
      fragments and continuous cell lines to atractyloside.
AB  - The consumption of plants containing the diterpenoid atractyloside (ATR) causes
      selective proximal tubule injury, renal failure and death in humans. We have
      compared the effects of ATR in freshly isolated renal proximal tubules and
      glomeruli from rat and also in cell lines: NRK, derived from the proximal
      tubules, and MDBK and MDCK more closely representing the distal nephron. The
      effects of ATR (10-500 microM) on proximal tubules and glomeruli were assessed by
      changes in lipid peroxidation, de novo protein synthesis and the leakage of
      alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate dehydrogenase
      (GDH) and N-acetyl-beta-D-glucosaminidase (NAG). The susceptibility of NRK, MDBK
      and MDCK cell lines to ATR was assessed by the 3-(4,5-dimethylthiazole-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assay, measuring mitochondrial reduction.
      Enzyme leakage was the most sensitive of the markers of cell injury in fresh
      fragments and ranked LDH > GDH > ALP > NAG in proximal tubules. As little as 20
      microM ATR caused significant enzyme leakage from proximal tubules, but there
      were no increases in enzyme leakage from glomeruli at concentrations < and = 500
      microM ATR. De novo protein synthesis was only inhibited 50% at ATR concentration
      > 5 mM in the proximal tubules, but there were no effects in glomeruli.
      Malondialdehyde production was significantly elevated at 1 mM ATR for proximal
      tubules, and 500 microM for glomeruli. NRK cells were sensitive to ATR (IC50, 120
      microM), but MDBK or MDCK cells were unaffected by < and = 1 mM of this
      diterpenoid. Both freshly isolated fragments and continuous cell lines
      representing the proximal tubules are more sensitive to ATR than either glomeruli
      or cells representing the distal nephron. These data also show that protein
      synthesis is a less specific and sensitive measure of ATR cytotoxicity than
      enzyme leakage in fragments. MTT reduction to formazan was the most sensitive in
      the NRK cell line. The low levels of lipid peroxidation products in proximal
      tubular fragments or sensitive renal cell lines at toxic levels of ATR suggest
      that oxidative injury is not a key mechanism.

PMID- 9010591
TI  - Biochemical alterations as measures of acute and subacute hepatotoxicity of 1,3
      dibromobenzene in rat.
AB  - Rats were used to study acute and subacute hepatotoxicity of 1,3-dibromobenzene
      (1,3-dBB). In the single-exposure experiment, maximum hepatic 1,3-dBB
      concentrations were found to occur 1 to 12 h after the exposure, depending on the
      dose. Maximum concentrations of covalently bound adducts were reached after 12 h.
      Depletion of hepatic glutathione (GSH) content occurred during the first 24 h
      following the exposure, but was not accompanied by changes in alanine
      aminotransferase (ALT) activity. The increased number of doses also did not
      result in necrotic lesions of the liver. In the subacute (28-day) experiment,
      higher hepatic GSH levels and increased blood serum gamma-glutamyltransferase
      (gamma-GT) activity were observed. Exposure to 1,3-dBB resulted in increased
      porphyrin excretion in urine, without accompanying increase in the removal of
      delta-aminolevulinic acid (AlA-U). The results indicate that subacute exposure to
      1,3-dBB produces porphyrinuria in the rat.

PMID- 9010592
TI  - Comparison of the toxicity of allyl alcohol, coumarin and menadione in precision
      cut rat, guinea-pig, cynomolgus monkey and human liver slices.
AB  - The toxicity of allyl alcohol, coumarin and menadione has been studied in
      precision-cut liver slice cultures. Liver slices were prepared from male Sprague
      Dawley rats, male Dunkin-Hartley guinea-pigs and from samples of Cynomolgus
      monkey and human liver using a Krumdieck tissue slicer. The liver slices were
      cultured with the test compounds for 24 h in a dynamic organ culture system.
      Toxicity was assessed by measurement of protein synthesis, potassium content and
      the MTT assay. At the concentrations examined, menadione produced marked toxicity
      in liver slices from all four species, whereas rat liver slices were less
      susceptible to allyl alcohol toxicity. Coumarin produced concentration-dependent
      toxic effects in rat and guinea-pig liver slices, whereas Cynomolgus monkey and
      human liver slices were relatively resistant, especially at low coumarin
      concentrations. At some concentrations of the test compounds examined, the MTT
      assay appeared to be a less sensitive indicator of toxicity than either protein
      synthesis or potassium content. These results demonstrate the usefulness of
      precision-cut liver slices for assessing species differences in xenobiotic
      induced toxicity.

PMID- 9010593
TI  - Toxicokinetics of p-tert-octylphenol in male Wistar rats.
AB  - Only weak oestrogenic activity has been reported for p-alkylphenols compared with
      the physiological hormone 17 beta-estradiol. Despite the low potency, there is
      concern that due to bioaccumulation oestrogenically efficient blood levels could
      be reached in humans exposed to trace levels of p-alkylphenols. To address these
      concerns, toxicokinetic studies with p-tert-octylphenol [OP; p-(1,1,3,3
      tetramethylbutyl)-phenol] as a model compound have been conducted in male Wistar
      rats. OP blood concentrations were determined by GC-MS in rats receiving either
      single oral (gavage) applications of 50 or 200 mg OP/kg body wt or a single
      intravenous injection of 5 mg/kg body wt. The OP blood concentration was
      approximately 1970 ng/ml immediately after a single intravenous application,
      decreased rapidly within 30 min, and was no longer detectable 6-8 h after
      application. The curve of blood concentration vs time was used to calculate an
      elimination half-life of 310 min. OP was detected in blood as early as 10 min
      after gavage administration, indicating rapid initial uptake from the
      gastrointestinal tract; maximal blood levels reached 40 and 130 ng/ml after
      applications of 50 and 200 mg/kg, respectively. Using the area under the curve
      (AUC) of blood concentration vs time, low oral bioavailabilities of 2 and 10%
      were calculated for the 50 and 200 mg/kg groups, respectively. OP toxicokinetics
      after repeated administration was investigated in male Wistar rats receiving
      daily gavage administrations of 50 or 200 mg OP/kg body wt for 14 consecutive
      days. Profiles of OP blood concentration vs time determined on day 1 and day 14
      were similar, indicating that repeated oral gavage administration did not lead to
      increased blood concentrations. Another group of rats received OP via drinking
      water saturated with OP (approximately 8 mg/l, corresponding to a mean daily dose
      of approximately 800 micrograms/kg) over a period of up to 28 days. OP was not
      detected in any blood sample from animals treated via drinking water (detection
      limit was 1-5 ng/ml blood). OP concentrations were also analysed in tissues
      obtained from the repeated gavage (14 days) and drinking water groups (14 and 28
      days). In the 50 mg/kg group, low OP concentrations were detected in fat and
      liver from some animals at average concentrations of 10 and 7 ng/g tissue,
      respectively. OP was not detected in the other tissues analysed from this group.
      In the 200 mg/kg group, OP was found in all tissues analysed except testes (fat,
      liver, kidney, muscle, brain and lung had average concentrations of 1285, 87, 71,
      43, 9 and 7 ng/g tissue, respectively). OP was not detected in tissues of animals
      receiving OP via drinking water for 14 or 28 days, except in muscle and kidney
      tissue of one single animal receiving OP for 14 days. Using rat liver fractions
      it was demonstrated that OP was conjugated via glucuronidation and sulphation in
      vitro. A Vmax of 11.24 nmol/(min * mg microsomal protein) and a Km of 8.77
      mumol/l were calculated for enzyme-catalysed OP glucuronidation. For enzyme
      catalysed sulphation, a Vmax of 2.85 nmol/(min * mg protein) and a Km of 11.35
      mumol/l were calculated. The results indicate that OP does not bioaccumulate in
      rats receiving low oral doses, in agreement with the hypothesis of a rapid first
      pass elimination of OP by the liver after oral ingestion, via glucuronidation and
      sulphation. Only if these detoxification pathways are saturated may excessive
      doses lead to bioaccumulation.

PMID- 9010594
TI  - Glutathione S-transferase GSTM1 and GSTT1 null genotypes as potential risk
      factors for urothelial cancer of the bladder.
AB  - One-hundred-and-thirteen patients with cancer of the urinary bladder (cases) were
      examined with respect to the frequency of null genotypes of the polymorphic
      glutathione S-transferases GSTM1 and GSTT1. The allelic background in the German
      population of the area was evaluated by analysing 170 newborns (controls). The
      frequency of GSTM1 and GSTT1 null genotypes in this population, using methods
      based upon internal standard controlled polymerase chain reaction (PCR), was 0.54
      and 0.18 respectively. An elevated relative bladder cancer risk of GSTM1 null
      genotype carriers was indicated by comparison of this background with the data of
      the bladder cancer cases (OR = 1.81; 95% CI [1.10, 2.98]; p = 0.019). The
      frequencies of the GSTT1 null genotype in the total group of bladder cancer cases
      versus controls did not differ statistically. However, a significantly higher
      relative risk of bladder cancer for the GSTT1 null genotype was detected in the
      cases-subgroup of non-smokers (OR = 3.84; 95% CI [1.21, 12.23]; p = 0.023). Thus,
      the GSTT1 null genotype might represent a minor risk factor for human bladder
      cancer which should be further investigated.

PMID- 9010595
TI  - 2-Chloroacetophenone is an effective glutathione depletor in isolated rat
      hepatocytes.
AB  - The glutathione (GSH) depleting effect of 2-chloroacetophenone (CN) was studied
      in freshly isolated rat hepatocytes. CN proved to be more effective in depleting
      GSH than diethylmaleate, phorone or styrene oxide. The reaction between GSH and
      CN followed a 1:1 stoichiometry, allowing adjustment of cellular GSH
      concentrations at distinct levels. After incubating cells (8 mg protein/ml) with
      200 mumol CN/l for 5 min, GSH depletion was almost complete without signs of
      cytotoxicity. At 300 mumol/l CN, GSH depletion persisted, and cytotoxicity
      occurred after 30 min. Activities of cytochrome P450 dependent enzymes, even at
      concentrations up to 500 mumol CN/l, were only marginally affected. Therefore, CN
      is of particular value for in vitro studies at decreased availability of GSH.

PMID- 9010596
TI  - The roles of individual amino acids in altering substrate specificity of the P450
      2a4/2a5 enzymes.
AB  - A single amino acid substitution is sufficient to alter substrate specificity of
      P450 enzymes. Mouse P450 2a5, for example, has its substrate specificity
      converted from coumarin 7- to testosterone 15 alpha-hydroxylase activity by the
      substitution of Phe at position 209 to Leu. Furthermore, placing Asn at this
      position confers a novel corticosterone 15 alpha-hydroxylase activity to this
      P450. Recent site-directed mutational studies show the presence of the
      topologically common residues, each of which can determine the specificities of
      various mammalian P450s. For instance, residue 209 (in 2a5) corresponds to a
      residue at position 206 in rat P4502B1 that regulates its steroid hydroxylase
      activity. High substrate specificity often observed in an individual P450,
      therefore, can be determined and altered by the identities of a few critical
      residues. The structural flexibility of the substrate-heme pocket may also
      provide P450 enzymes with the ability to display a broad range of substrate
      specificities. Understanding the underlying principles whereby the flexible
      pocket determines P450 activities may lead us to the prediction of P450
      activities based on the identities of key amino acid residues.

PMID- 9010597
TI  - Conformational dynamics in cytochrome P450-substrate interactions.
AB  - There now are four known cytochrome P450 crystal structures. Two of these,
      P450cam and P450eryF, are substrate-bound while P450terp and the heme domain of
      P450BM-3 are substrate-free. Here we describe a preliminary analysis of the
      P450BM-3 heme domain complexed with the 16-carbon fatty acid substrate,
      palmitoleic acid. A comparison of the substrate-free and -bound structures shows
      that a large conformational change in the substrate access channel accompanies
      substrate binding. This new information, together with the substrate-bound
      structures of P450cam and P450eryF, reveals which regions of P450 are the most
      important in controlling the dynamics of substrate binding and recognition.

PMID- 9010598
TI  - Carbon monoxide binding to cytochrome P450BM-3: evidence for a substrate
      dependent conformational change.
AB  - The kinetics of carbon monoxide binding to cytochrome P450BM-3 in the presence
      and absence of substrate has been investigated using flash photolysis. The second
      order kinetics for CO association with the substrate-free form of the protein
      appear biphasic. Deconvolution into two exponentials yields fast and slow rate
      constants of 11.1 +/- 0.6 x 10(6) M-1 s-1 and 3.5 +/- 0.2 x 10(6) M-1 s-1,
      respectively with 52% of the signal being attributed to the fast phase.
      Interestingly, upon binding of a substrate such as laurate, the second order
      kinetics become monophasic, with a value of 3.5 x 10(6) M-1 s-1, which are
      similar to the slow rate found in the substrate-free form of the protein. We have
      also examined the geminate CO rebinding kinetics in the presence and absence of
      various substrates. In the substrate-free form of the overall geminate yield is
      30%, and addition of a substrate increases the geminate yield to roughly 50%.
      Both the substrate-free and substrate-bound forms exhibit complex geminate
      kinetics which cannot be described by a simple three-state kinetic model.
      Extension of this model to include four states is required. The addition of
      substrate causes an increase in the geminate rate constants resulting in a larger
      geminate amplitude when compared to the substrate-free form. There is also
      evidence for a correlation between the volume occupied by the substrate and the
      geminate rate constants. These results are discussed in terms of substrate
      dependent conformational changes in cytochrome P450BM-3 and the overall energy
      landscape of the hemoprotein which couples to conformer equilibria.

PMID- 9010599
TI  - Cytochrome P450 conformation and substrate interactions as probed by CO binding
      kinetics.
AB  - The kinetics of CO binding to cytochrome P450, as measured by the flash
      photolysis technique, is a powerful probe of P450 structure-function
      relationships. The kinetics are sensitive to P450 conformation and dynamics and
      are modulated by P450 interactions with substrates and other components of the
      microsomal membrane. Application of a difference method to kinetic data analysis
      distinguishes the kinetic behavior of individual P450 forms in the microsomal
      membrane. This approach shows that substrates differentially modulate the
      kinetics via: 1) changes in P450 conformation/dynamics that either accelerate or
      reduce the binding rate; and/or 2) steric effects that reduce the rate. Both
      mechanisms are observed, the relative contributions of each varying in a
      substrate- and P450-dependent manner. In addition to microsomes, substrate
      interactions with individual P450s can be similarly probed using expressed P450s.
      Experiments with baculovirus-expressed human P450 3A4 show that this P450
      consists of multiple conformers with distinct substrate specificities, an
      observation which provides a basis for its recognition of a wide array of
      structurally diverse substrates. These studies thus demonstrate the utility of CO
      binding kinetics in elucidating fundamental P450-substrate interactions in a
      biological membrane environment.

PMID- 9010600
TI  - Rational approach to improving reductive catalysis by cytochrome P450cam.
AB  - Although halogenated hydrocarbons are noted for low chemical reactivity, small
      amounts are toxic to humans. Cytochromes P450 have been implicated in
      transforming these compounds to more reactive species, under anaerobic
      conditions, through reduction at the heme. A significant amount of effort has
      been directed toward turning this catalytic ability to our advantage by
      engineering P450 variants than can efficiently remediate these compounds in situ,
      before they come in contact with the human population. We have taken a 'rational'
      approach to this problem, in which a combination of theory and molecular modeling
      is applied to identify which properties of the enzyme have the greatest influence
      over reductive dehalogenation. Recent progress in this area is briefly reviewed.
      Two novel mutants, incorporating tryptophan (positions 87 and 396) and histidine
      (position 96, neutral and protonated) amino acid substitutions in the active
      site, are proposed and evaluated using molecular dynamics simulations. The upper
      bound on rate enhancement relative to wild-type is estimated in each mutant using
      electron transfer theory. The most significant rate enhancement is predicted for
      the His 96 mutant in the protonated state; while some His residues of certain
      proteins exhibit a pKa high enough to support a large protonated population, such
      information is not presently available for this proposed mutant.

PMID- 9010601
TI  - A structure-based model for cytochrome P450cam-putidaredoxin interactions.
AB  - Putidaredoxin (Pdx) is a Fe2S2 ferredoxin which acts as the physiological
      reductant of cytochrome P-450cam (CYP101). A model for the solution structure of
      oxidized Pdx has been determined using NMR methods (Pochapsky et al (1994)
      Biochemistry 33, 6424-6432). 1H-15N correlations and redox-dependent amide
      exchange rates have also been described (Lyons et al (1996) Protein Sci 5, 627
      639). Data obtained from mutagenesis and kinetic measurements concerning the
      interactions of Pdx and CYP101 are summarized. A model for the structure of the
      homologous ferredoxin adrenodoxin (Adx) is also described, and data concerning
      Adx activity are discussed in relation to this structure. The structures of Pdx
      and CYP101 were used as starting points for molecular modeling and molecular
      dynamics simulations. Close approach between the metal centers of the two
      proteins and interaction between aromatic residues on the surfaces of the
      proteins are premised. The resulting complex exhibits three intermolecular salt
      bridges, five intermolecular hydrogen bonds and a 12 A distance between the metal
      centers. The first direct observations of interaction between Pdx and CYP101 (by
      two-dimensional NMR of 15N-labeled Pdx in solution with CYP101) are described.
      The results of the NMR experiments indicate that conformational gating of the
      electron transfer complex between CYP101 and Pdx may be important.

PMID- 9010602
TI  - Interactions of cytochrome P450 2B4 with NADPH-cytochrome P450 reductase studied
      by fluorescent probe.
AB  - A new method for monitoring the formation of the cytochrome P450 complexes with
      NADPH-cytochrome P450 reductase (NCPR) is introduced. The method is based on the
      quenching of fluorescence of NCPR labelled with 7-ethylamino-3-(4'
      maleimidilphenyl)-4-methylcoumarin maleimide (CPM). In a monomerized soluble
      reconstituted system in the absence of phospholipid, cytochrome P450 2B4 and
      NCPRcpm were shown to form 1:1 complexes with a Kd of 0.038 microM. Formation of
      the complex follows the kinetics of reversible second order transition with k(on)
      = 6.5 10(5) M-1 s-1. Application of high hydrostatic pressure induces
      dissociation of the complex (delta V degrees = -65 mL/mol). Succinylation of the
      hemoprotein increases the value of Kd to 0.5 microM primarily by decreasing
      k(on). In contrast to what was shown for intact 2B4, rising pressure does not
      take apart succinylated hemoprotein and NCPRcpm molecules, but causes some
      internal transition in their complex that diminishes the quenching. This
      transition is characterised by a very large volume change (delta V degrees = -155
      mL/mol). The following conclusions were drawn: 1) a molecule of 2B4 contains two
      distinct contact regions involved in the interactions with NCPR. Only one of
      these regions is polar and highly hydrated in unbound hemoprotein; 2)
      interactions of the polar regions of 2B4 and NCPR are necessary to bring CPM
      labelled cysteine of NCPR in short distance of the heme of 2B4; and 3) some of
      the lysine residues located in the proximity of the polar binding regions are
      apparently involved in the formation of the internal salt bridges in the molecule
      of 2B4.

PMID- 9010603
TI  - Domain-domain interaction in cytochrome P450BM-3.
AB  - The influence of ionic strength on the interactions between individually
      expressed functional domains of cytochrome P450BM-3 and the domains in the
      holoenzyme has been analyzed by spectrophotometric and fluorometric techniques.
      High ionic strength facilitated electron transfer from NADPH to the FMN moiety of
      the reductase domain (BMR) of P450BM-3 and did not affect the first electron
      transfer from FMN to the heme in the holoenzyme. The cytochrome c reductase
      activity of the holoenzyme was higher than that of BMR within the range of ionic
      strength tested. Two electron reduced FMN, ie incapable of transferring electrons
      to the heme iron of P450BM-3, was found to be capable of reducing cytochrome c.
      Fluorometric studies of the domains of P450BM-3 revealed that: 1) fluorescence of
      FAD is completely quenched in the FAD-binding domain; 2) BMR gives the highest
      quantum yield which is 2.5 times higher than that of the FMN-binding domain
      alone; 3) the heme domain (BMP) quenches a half and three-fourths of the
      fluorescence of the FMN in the linked BMP/FMN-binding domain and in the
      holoenzyme, respectively; 4) maximal quenching of the flavin fluorescence in the
      mixtures containing different combinations of the functional domains of P450BM-3
      was observed at high ionic strength. The results indicate that the flavins in
      P450BM-3 are not in close proximity. Moreover, the presence of the FAD domain
      causes structural changes in the FMN domain resulting in an increase in the
      polarity of the FMN environment in BMR and may promote the interaction between
      FMN- and heme-binding domains in P450BM-3. Such domain interaction may facilitate
      the delivery of electrons from the FMN semiquinone to the heme and prevent the
      formation of the inactive two electron reduced species of the FMN. Thus, the high
      turnover number of P450BM-3 and tight coupling of the monooxygenation reaction
      are provided not only by the mechanism of reduction of the heme by the reductase
      but also by domain-domain interaction.

PMID- 9010604
TI  - Antigenic mapping of bacterial and animal cytochromes P-450.
AB  - A peptide scanning (PEPSCAN) approach was used for antigenic mapping of two
      hepatic microsomal cytochromes P450 (rab1A2 and rab2B4) and the microbial
      cytochrome from Pseudomonas putida (P450 101 or P450cam). This approach includes
      simultaneous synthesis of pin-linked overlapping hexapeptides covering the whole
      sequences of three P450s and testing them by ELISA with corresponding polyclonal
      antisera. Microsomal cytochrome P450 maps were shown to vary depending on an
      antiserum used for testing the peptides, however, the most active linear B
      epitopes were revealed with antisera from two animal species used. P450 linear B
      epitopes were classified into individual and group-specific epitopes. While
      almost all P450 101 linear antigenic determinants are unique for this protein,
      rab1A2 and rab2B4 contain epitopes both individual for each protein, and
      subfamily- or even family-specific epitopes. These results point out the
      possibility of producing both monospecific and group-specific antipeptide
      antibodies against different P450s. The antigenic map of P450 101 was
      superimposed on the structural-functional map of this protein. Its linear B
      epitopes were shown to coincide with boundaries of secondary structure elements,
      with surface-located, water accessible regions and with sites responsible for
      intermolecular interactions in the Pseudomonas putida monooxygenase system.
      Several known or predicted functionally active sites in microsomal cytochrome
      P450 rab1A2 and rab2B4 were also shown to coincide with linear B-epitopes. The
      peculiarities of epitope locations in the protein tertiary structure will allow
      to predict antigenic regions starting from protein structural information and
      vice versa, to structural protein models in accordance with antigenic mapping
      results. Antigenic regions which coincide with sites responsible for
      intermolecular interactions in monooxygenase systems may be synthesized as
      separate peptides and used as blockers of such interactions.

PMID- 9010605
TI  - NMR studies of recombinant cytochrome P450cam mutants.
AB  - In the active center of cytochrome P450cam, Thr-252 is one of the conserved amino
      acid residues in the cytochrome P450 superfamily and plays a key role in the
      hydroxylation of camphor. T252A mutant, in which Thr-252 is replaced by alanine,
      consumed O2 at a rate comparable to that of the wild-type enzyme, whereas the
      amount of exo-5-hydroxycamphor formed was less than 10% of that formed by the
      wild-typed enzyme and H2O2 is the main product in the hydroxylation reaction.
      H2O2 was also yielded by the valine mutant and the consumption rate of O2 was
      much lower than that for the wild-type enzyme (Imai et al (1989) Proc Natl Acad
      Sci USA 86, 7823-7827). On the basis of the 1H- and 15N-NMR spectra, it was
      revealed that the anionic nature of the axial thiolate and the heme-environmental
      structures were substantially affected in the absence of d-camphor by the amino
      acid substitution at 252 Thr. In T252A mutant, however, the binding of camphor
      reduced these conformational alterations in the heme vicinity, probably due to
      the formation of interactions between camphor and enzyme. On the other hand,
      T252V mutant still exhibited large reduction of the anionic nature of the axial
      ligand in the presence of d-camphor and structural changes around heme were also
      enhanced, since the affinity of the valine mutant to d-camphor was low. These
      results imply that the hydrophobic and/or steric effects of the valine residue at
      252 interfere with interactions around heme and camphor binding sites, which
      corresponds to the larger functional defects for T252V mutant.

PMID- 9010606
TI  - Computer modeling of 3D structures of cytochrome P450s.
AB  - The understanding of structure-function relationship of enzymes requires detailed
      information of their three-dimensional structure. Protein structure determination
      by X-ray and NMR methods, the two most frequently used experimental procedures,
      are often difficult and time-consuming. Thus computer modeling of protein
      structures has become an increasingly active and attractive option for obtaining
      predictive models of three-dimensional protein structures. Specifically, for the
      ubiquitous metabolizing heme proteins, the cytochrome P450s, the X-ray structures
      of four isozymes of bacterial origin, P450cam, P450terp, P450BM-3 and P450eryF
      have now been determined. However, attempts to obtain the structure of mammalian
      forms by experimental means have thus far not been successful. Thus, there have
      been numerous attempts to construct models of mammalian P450s using homology
      modeling methods in which the known structures have been used to various extents
      and in various strategies to build models of P450 isozymes. In this paper, we
      review these efforts and then describe a strategy for structure building and
      assessment of 3D models of P450s recently developed in our laboratory that
      corrects many of the weaknesses in the previous procedures. The results are 3D
      models that for the first time are stable to unconstrained molecular dynamics
      simulations. The use of this method is demonstrated by the construction and
      validation of a 3D model for rabbit liver microsomal P450 isozyme 2B4,
      responsible for the oxidative metabolism of diverse xenobiotics including widely
      used inhalation anesthetics. Using this 2B4 model, the substrate access channel,
      substrate binding site and plausible surface regions for binding with P450 redox
      partners were identified.

PMID- 9010607
TI  - Scanning tunneling microscopy study of cytochrome P450 2B4 incorporated in
      proteoliposomes.
AB  - In the present paper, the application of scanning tunneling microscopy in
      cytochrome P450s membrane topology is discussed. The method enables visualization
      of heme location in the lipid-bilayer-incorporated protein. It is supposed that
      the membrane-bound cytochrome P450 on the tunneling microscope substrate should
      behave as 'molecular diode'. A model explaining the liposome and the
      proteoliposome images observed is proposed.

PMID- 9010608
TI  - Peroxynitrite inhibition of nitric oxide synthases.
AB  - Peroxynitrite (PN) can be formed under mainly pathophysiological conditions from
      nitric oxide (NO) and superoxide anion and may be responsible for oxidative
      modifications of biomolecules. Preparations of nitric oxide synthases from
      porcine cerebellum (nNOS), bovine aortic endothelium (eNOS) and cytokine-treated
      murine macrophages (iNOS) were inhibited by PN in their ability to transform
      arginine to citrulline and nitric oxide with IC50 values of 15, 28, and 10
      microM, respectively. Glutathione, bovine serum albumin and tyrosine provided
      varying degrees of protection in the three preparations. Intact endothelial
      cells, upon exposure to PN, rapidly lost their glutathione content but protein-SH
      groups and eNOS activity remained largely unaffected. Destruction of the heme
      thiolate catalytic site was observed when nNOS was exposed to PN suggesting that
      the irreversible oxidation of this bond may be the common mechanism of NOS
      inhibition.

PMID- 9010609
TI  - Two isozymes of P450nor of Cylindrocarpon tonkinense: molecular cloning of the
      cDNAs and genes, expressions in the yeast, and the putative NAD(P)H-binding site.
AB  - The cDNAs and genes for two isozymes of cytochrome P450nor of the fungus
      Cylindrocarpon tonkinense, P450nor1 and P450nor2, were cloned and sequenced.
      Their deduced amino acid sequences respectively showed 83 and 70% identity to
      that of P450nor of Fusarium oxysporum, and 69% identity to each other. The genes
      for P450nor1 and P450nor2 were termed, respectively, CYP 55A2 and CYP 55A3. The
      cDNA for P450nor1 contained a targeting-like presequence upstream the N-terminus
      of mature protein whereas that for P450nor2 did not, suggesting their different
      intracellular localisations. We also succeeded in expressing these P450nor
      isoforms in the host-vector system of the yeast Saccharomyces cerevisiae. We
      purified one of the recombinant proteins, P450nor of F oxysporum. Little
      difference could be observed between the native and recombinant proteins in
      catalytic and spectroscopic properties. We constructed chimeric proteins of
      P450nor of F oxysporum and P450nor2 which are different in their specificity
      against the electron donors: reduced pyridine nucleotides. The specificity of
      chimeric proteins against NADH/NADPH showed that the specificity is determined by
      the N-terminal half of protein. We found a consensus amino acid sequence between
      three isoforms of P450nor, A-X-G-X-X-A, similar to the NAD-binding motif G-X-G-X
      X-G/A in the region that corresponds to the B'-helix in P450cam.

PMID- 9010610
TI  - Ibuprofen and diclofenac sodium in the treatment of osteoarthritis: a comparative
      trial of two once-daily sustained-release NSAID formulations.
AB  - An investigator-blind, parallel-group, multicentre study was undertaken to
      compare the efficacy and tolerability of once-daily, sustained-release (s-r)
      ibuprofen and diclofenac sodium in patients (mean age 59.8 years) suffering from
      painful osteoarthritis affecting chiefly the knee and/or hip. Patients attending
      eight Swiss centres received either two s-r tablets of ibuprofen (daily dose 1600
      mg; n = 30) or a single s-r diclofenac 100 mg tablet (n = 31) each evening for 21
      days. Clinical assessments were performed prior to initiating therapy and after 7
      and 21 days of treatment. Both treatments were efficacious, but statistically
      significant differences in favour of s-r ibuprofen were observed for the
      principal measure of efficacy, the investigator's assessment of the overall
      change in clinical condition; by Day 21, 37% of ibuprofen-treated patients vs 10%
      of diclofenac-treated patients were 'much improved' (p = 0.04). Patients'
      assessments of the efficacy of their treatment also favoured s-r ibuprofen at Day
      7 for the relief of night pain (p = 0.048), at Day 21 for alleviation of day pain
      (p = 0.006) and for the ability to carry out normal activities (p = 0.01), and at
      both Days 7 and 21 for quality of sleep (p = 0.04 and 0.03, respectively). The
      patients' overall opinion of treatment was also significantly in favour of s-r
      ibuprofen, which was rated 'good or excellent' by 80% (24/30), compared with only
      38% of patients (11/29) receiving s-r diclofenac sodium (p = 0.002). Two patients
      (6%) receiving s-r diclofenac sodium ceased treatment owing to dizziness and
      severe diarrhoea, respectively; there were no withdrawals in the ibuprofen
      treated group. Ten (32%) patients in the s-r diclofenac group reported a total of
      12 adverse events (mostly gastrointestinal in nature), compared with three (10%)
      patients in the s-r ibuprofen group who reported only three events (abdominal
      pain, insomnia and constipation). In conclusion, although both NSAID treatments
      improved the clinical condition of patients with painful osteoarthritis,
      statistically significant differences in favour of once-daily s-r ibuprofen (1600
      mg) were demonstrated in terms of efficacy, indicating a potential therapeutic
      advantage for this formulation. Ibuprofen was also better tolerated than
      diclofenac sodium (100 mg/day), the latter being associated with gastrointestinal
      side effects in a significant proportion of patients. Sustained-release ibuprofen
      (Brufen Retard) thus represents an important addition to the available
      therapeutic armamentarium of once-daily NSAID formulations.

PMID- 9010611
TI  - Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy
      versus combination therapy.
AB  - A multinational, double-blind, randomised study was conducted to investigate the
      efficacy and safety of a low-dose combination of the angiotensin converting
      enzyme inhibitor, ramipril, and the calcium antagonist, felodipine ER, in 642
      patients with mild to moderate hypertension [supine diastolic blood pressure
      (DBP) = 95-115 mm Hg]. After a 4-week single-blind placebo run-in, patients were
      randomly allocated to once-daily felodipine extended release (ER; 2.5 mg),
      ramipril (2.5 mg) or felodipine ER/ramipril (2.5/2.5 mg) for 12 weeks. In the
      intention-to-treat analysis, mean DBP decreased significantly (p < 0.0001) after
      felodipine ER, ramipril and the combination (-9.1, -9.8 and -11.4 mm Hg,
      respectively). The decrease was significantly greater with the combination than
      with felodipine ER monotherapy (p = 0.02). The number of responding patients
      (final DBP < or = 90 mm Hg or a decrease of > or = 10 mm Hg) was also higher with
      the combination than with felodipine ER or ramipril monotherapy (65.1%, 53.1%,
      55.7%, respectively). There were no differences between the three groups with
      respect to the incidence of adverse events overall or those considered treatment
      related. There were fewer cases of peripheral oedema with combination therapy
      than with felodipine ER monotherapy. Thirty-three patients (5.1%) withdrew from
      the study because of adverse events, but there was no clear pattern with regard
      to the specific events leading to withdrawal. There were no clinically relevant
      changes in laboratory or clinical safety variables. Ramipril/felodipine ER
      2.5/2.5 mg is an appropriate starting dosage when initiating combination
      antihypertensive therapy.

PMID- 9010612
TI  - A randomized, double-blind placebo controlled cross-over study to investigate the
      effects of RW94 on the absorption of dietary fat in healthy volunteers.
AB  - RW94 is a permitted additive in the food industry, which precipitates fatty acids
      in vitro. In vivo, this could result in reduced fatty acid absorption by the
      body, and may, therefore, influence the amount of fat excreted in the faeces. An
      investigation into the effects of RW94 on bodily fat absorption and excretion was
      undertaken. The safety, tolerability and efficacy of the product was compared
      with placebo in a group of 12 healthy volunteers, randomly assigned to receive
      either RW94 or placebo for a period of four days when dietary fat intake was
      controlled. After a 10-day washout period, the randomly assigned groups were
      crossed over to receive placebo and RW94, respectively, for a second 4-day
      period, when fat intake was similarly controlled. Five grams of RW94 administered
      orally 30 min after each meal resulted in a statistically significant increase in
      the amount of excreted faecal lipids compared with placebo (p < 0.05). Following
      high fat intake, total blood cholesterol was predictably raised in both placebo
      and RW94 groups, but was less markedly raised with RW94 than placebo. All
      subjects lost body weight during the study, but the loss while consuming RW94 was
      significantly greater (p < 0.05) than while consuming placebo. All subjects found
      the treatments acceptable, though an increased incidence of flatulence, rumbling
      stomach and abdominal discomfort was noted with RW94 compared with placebo. RW94
      was comparable with placebo in respect of safety.

PMID- 9010613
TI  - Proposal of an algorithm to help the choice of the best transfusion strategy.
AB  - Autologous blood donation (ABD) reduces both the real and perceived risks of
      allogeneic blood exposure, although wasted units increase overall costs. Wastage
      of autologous blood can be contained by using rational blood ordering and
      collection strategies. These identify procedures with transfusion requirements,
      utilizing ABD predeposit in patients undergoing surgery for which the need for
      blood transfusion has been clearly established, and where the average blood loss
      for each procedure has been determined. ABD programmes can be optimized by
      adopting a personalized approach for each individual patient. The predicted and
      tolerated blood loss is calculated for each patient, and the difference between
      the two determines the patient's transfusion need. Taking into account the type
      of surgery, time to surgery and the clinical condition of the patient, the best
      and most cost-conscious transfusion strategy can then be determined. Options
      include: reducing the blood loss pharmacologically, transfusing allogeneic blood,
      using autologous blood from a variety of techniques, using recombinant
      erythropoietin (epoetin alfa) to increment baseline haematocrit (Hct) or to
      increase the volume of predonated blood, and using blood substitutes in addition
      to autotransfusion techniques. Autotransfusion techniques available include ABD
      predeposit, normovolaemic haemodilution and perioperative salvage. ABD predeposit
      may be limited by the delay in the natural erythropoietic response to allow
      recovery of red cells collected. Together with adequate iron support, epoetin
      alfa accelerates recovery of the Hct and increases the tolerated blood loss. The
      availability and judicious use of these blood conservation strategies provide for
      both effective and cost-conscious blood transfusion strategies.

PMID- 9010614
TI  - Lipoprotein(a) in cirrhosis. A new index of liver functions?
AB  - Over the last few years, lipoprotein(a) [Lp(a)] levels have been investigated
      because clinical studies have related it to increased cardiovascular and
      cerebrovascular risk. Although it is known that serum Lp(a) concentrations are
      controlled genetically, little is known about its metabolism. We studied changes
      in the lipid profile and Lp(a) values in 57 patients (34 males and 23 females)
      affected by cirrhosis of the liver subdivided into Child's classes in order to
      assess whether this lipoprotein is sensitive to reduced liver protein synthesis.
      The patients presented with low total cholesterol, normal HDL-cholesterol (HDL
      c), LDL-cholesterol (LDL-c), triglycerides, apoprotein A1 (Apo-A1) and apoprotein
      B100 (Apo-B100) concentrations, while Lp(a) concentrations seemed elevated.
      Grouping the patients into Child's classes revealed that all the lipid parameters
      investigated reduced as the disease progressed. Lp(a) reduced significantly
      between Child's Classes I and II and seems to be correlated with the severity of
      cirrhosis and the clinical worsening of the patients' conditions. These findings
      suggest that Lp(a) is not only an index of atherosclerosis risk, but also plays a
      role in monitoring liver functions.

PMID- 9010615
TI  - Restenosis after coronary angioplasty.

PMID- 9010616
TI  - Molecular modelling study of the binding of inhibitors of aromatase to the
      cytochrome P-450 heme.
AB  - A novel molecular modelling study, involving inhibitors bound to a 'substrate
      heme complex', is described for steroidal and non-steroidal inhibitors of
      Aromatase (AR). Results with azole compounds such as CGS-16949A, and its
      derivatives, agree with recently reported studies that these compounds appear to
      utilise the steroid C(17) carbonyl binding region of the active site as opposed
      to the steroid C(3) carbonyl binding region. The study of Aminoglutethimide (AG)
      type compounds, however, suggests that they mimic the steroid C(17) and not the
      C(3) carbonyl group as suggested by previous workers. However, results with
      inhibitors based on pyridine ligands such as 3-(4'-pyridyl)-3-ethyl piperidine-2,
      6-dione (PYG), suggest that these compounds utilise the steroid C(3) carbonyl
      binding region and therefore agrees with previous reports. Consideration of the
      orientation of the R and S enantiomers of PYG is, however, found to be a reversal
      of that previously reported. Using inhibitors bound to the 'substrate-heme
      complex', and data from previous studies of derivatives of androstenedione,
      reasons for differences in activity of enantiomers of AG, PYG, N-octyl-3-(4'
      pyridyl)-3-ethyl piperidine-2, 6-dione, and 10-thiiranylestr-4-ene-3, 17-dione,
      as well as other potent and less potent inhibitors, are put forward.

PMID- 9010617
TI  - Functional design of potential inhibitors of human immunodeficiency virus (HIV)
      binding to CD4+ target cells: a molecular model of gp120 predicts ligand binding.
AB  - Inhibition of binding of HIV via gp120 to its principle cellular receptor, CD4,
      remains an attractive site for intervention in the viral replicative cycle
      despite the poor clinical trial results demonstrated to date for sCD4. Based on a
      model structure we recently proposed for gp120, we have examined the predicted
      binding sites for several synthetic and natural products which selectively bind
      to gp120 and inhibit binding to CD4. Correlation between the decrease in internal
      energies of the ligand/gp120 complexes versus the reported inhibitory constants
      of the known ligands suggests that the derived gp120 structure is sufficiently
      accurate to perform computer simulations to guide the design of improved ligands
      for the CD4 binding site on gp120.

PMID- 9010618
TI  - Cytotoxic quinolines (Part 3). Synthesis of 1-azolylalkyl-4(1H)-quinolones as
      cytotoxic agents.
AB  - A series of 1-azolylalkyl-4(1H)-quinolones has been synthesized and evaluated for
      cytotoxic activity both in vitro and in vivo. The effects on cytotoxicity of
      varying substitution on the quinoline moiety was investigated. The insertion of a
      5-amino group proved to be the most effective modification, resulting in a
      several-fold increase in cytotoxicity in vitro. Previously reported results
      indicated that the activity of this class of compounds may involve topoisomerase
      inhibition, but investigation of the current compounds has ruled out this
      possibility. One compound, 13, showed in vitro cytotoxicity notably superior to
      Adriamycin, however it demonstrated only slight or no in vivo efficacy depending
      on the model used.

PMID- 9010619
TI  - 2-(Substituted)amino-2,8-diazaspiro[4,5]decan-1,3-diones as potential muscarinic
      agonists: synthesis, modeling and binding studies.
AB  - A series of 2-(acyl)amino-8-substituted-2,8-diazaspiro[4,5]decan-1,3-diones (5a
      j), structurally related to the muscarinic agonist RS-86, was synthesized and
      compounds tested for their affinity towards muscarinic receptors. Though all
      compounds proved to be less active than the model in binding studies, only three
      derivatives (5a, b, c) being able to significantly displace 3H-QNB at mM
      concentration, their behaviour could be interpreted in terms of theoretical
      molecular descriptors computed on the basis of the suggestions coming from
      Molecular Dynamics simulations of ligand-receptor complexes.

PMID- 9010620
TI  - Substrate recognition mechanism of human beta-adrenergic receptor kinase 1 based
      on a three-dimensional model structure.
AB  - Although its detailed substrate specificity is not precisely known, beta
      adrenergic receptor kinase 1 phosphorylates beta 2-adrenergic receptors and other
      G protein-coupled receptors. To elucidate the ligand recognition mechanism of the
      enzyme and the consensus sequence required for substrates, a three-dimensional
      structure of the catalytic domain of the enzyme was modeled based on the X-ray
      crystal structure of the catalytic subunit of cyclic AMP-dependent protein kinase
      A. When the phosphorylation residue of the substrate was defined as the p
      position in the model of beta-adrenergic receptor kinase 1, the present study
      suggested that the consensus sequence recognized by this enzyme would consist of
      a basic residue at p-3 and an acidic residue at p-2.

PMID- 9010621
TI  - Synthesis and 5-HT3 affinity of new 3-substituted indoles at central nervous
      system.
AB  - A series of 3-imino and 3-aminomethyl-N-methylindoles, in which the amine
      substituents were 3-quinuclidyl and 1-adamantyl groups, were synthesized and
      their in vitro affinity towards 5-HT3 central receptors evaluated. Of the nine
      compounds tested, three caused displacement of 3H-BRL 43694 binding to 5-HT3. 2
      Chloro-3-(3-quinuclidylimino)-1-methylindole, 4, was the most potent compound
      with an IC50 = 5.15 10(-8) M. Moreover, the monoamine oxidase inhibition activity
      was tested and three compounds were shown to be MAO inhibitors, their IC50 was in
      the range of that of (-)-Deprenyl. Again, 4 was the most potent compound.
      Structure-activity relationships within the series are briefly discussed.

PMID- 9010622
TI  - Human UGT2B7 catalyzes morphine glucuronidation.
AB  - A human UDP-glucuronosyltransferase (UGT) catalyzing the glucuronidation of
      morphine has been identified. A full length cDNA was isolated from a human liver
      cDNA library and found to be identical to the UGT2B7 form having a tyrosine at
      position 288. This cDNA was transfected into HK 293 cells, and stable expression
      was achieved. Cell homogenates and membrane preparations from HK 293 cells
      expressing UGT2B7 catalyzed the glucuronidation of morphine and other clinically
      significant opioid agonists, antagonists, and partial agonists. UGT2B7 catalyzed
      morphine glucuronidation at the 3- and 6-hydroxy positions and also mediated the
      formation of codeine-6-glucuronide from codeine. This represents the first
      demonstration of a UGT capable of catalyzing the glucuronidation of both the 3-
      and 6-positions of opioids. Since humans excrete morphine-3-glucuronide and
      morphine-6-glucuronide after morphine administration, it is likely that UGT2B7 is
      a major isoform in humans responsible for the metabolism of this important drug
      and its surrogates.

PMID- 9010623
TI  - Glucuronidation of all-trans-retinoic acid and 5,6-epoxy-all-trans-retinoic acid.
      Activation of rat liver microsomal UDP-glucuronosyltransferase activity by
      alamethicin.
AB  - The effects of detergent, alamethicin (a channel-forming peptide), and the
      inducers phenobarbital and 3-methylcholanthrene on glucuronidation of all-trans
      retinoic acid (atRA) and 5,6-epoxy-atRA have been investigated using liver
      microsomes from Sprague-Dawley and Fischer 344 rats. Conditions for enzymatic
      glucuronidation were optimized for substrate concentration, protein, and time by
      using atRA and Sprague-Dawley microsomes. With detergent-activated Sprague-Dawley
      microsomes, 5,6-epoxy-atRA was shown to be a significantly better substrate than
      atRA for microsomal glucuronidation (263 vs. 116 pmol/mg/min for 5,6-epoxy-atRA
      and atRA, respectively). The product of incubation of microsomes with atRA and
      UDP-glucuronic acid was identified as a glucuronide by beta-glucuronidase
      hydrolysis and by HPLC analysis. Alamethicin was shown to be a highly effective
      activator of glucuronidation activity; atRA and 5,6-epoxy-atRA glucuronidation
      rates were increased 2- and 3-fold, respectively, compared with detergent
      activation. Alamethicin (but not detergent) significantly increased retinoid
      glucuronidation by microsomes from Fischer 344 rats treated with phenobarbital
      and 3-methylcholanthrene, compared with untreated controls. The two compounds
      were equally effective inducers of activity, although 5,6-epoxy-atRA was again
      the better substrate. The same control and induced Fischer rat microsomes were
      photolabeled with [32P]5-azido-UDP-glucuronic acid in the absence or presence of
      detergent, two concentrations of alamethicin, and a 10-fold molar excess of
      unlabeled UDP-glucuronic acid. Photoincorporation into microsomal proteins from
      detergent-disrupted induced microsomes was 2-3 times greater than that of
      controls. Alamethicin increased photoincorporation of the probe into UDP
      glucuronosyltransferase proteins an additional 1.5-2-fold in control and induced
      microsomes, compared with the respective detergent-activated samples.

PMID- 9010624
TI  - Immunolocalization of microsomal glutathione S-transferase in rat tissues.
AB  - Distribution of microsomal glutathione transferase (mGST) protein in rat tissues
      was investigated by immunohistochemistry. Studies on the localization of mGST are
      of interest because of its involvement in the detoxication and bioactivation of
      xenobiotics. mGST antigen was detected in the cytoplasm of some hepatocytes and
      in bile ducts. In kidney, focal staining of mGST was observed in distal tubules
      and collecting ducts. Cerebral cortical and cerebellar Purkinje neurons showed
      good immunoreactivity, and nuclear staining was observed in the choroid plexus.
      The antigen was detected in epithelial cells of respiratory bronchioles and in
      the crypt cells of the duodenum. Exocrine cells of the pancreas stained for mGST.
      Nuclear immunostaining for this protein was observed in primary spermatocytes.
      mGST antigen was detected in the cytoplasm of the adrenal medulla as a granular
      stain. Leydig and Sertoli cells in testis also stained for the antigen.
      Distribution of mGST protein differs from that observed with cytosolic
      transferases and may be important in determining cell-selective susceptibility to
      xenobiotics.

PMID- 9010625
TI  - Regulation of cytochrome P4501A1 expression in rat small intestine.
AB  - The predominant inducible cytochrome P450 (CYP) in rat small intestine is CYP1A1,
      which, when induced to elevated levels by xenobiotics or dietary constituents,
      has the potential to metabolize and consequently reduce the systemic uptake of
      low concentrations of orally ingested, bioactivatable polycyclic aromatic
      hydrocarbons and heterocyclic aromatic amines. We investigated the regulation of
      small intestinal CYP1A1 in an effort to develop its anticancer potential. The
      time courses of hepatic and intestinal CYP1A1 induction by beta-naphthoflavone
      (BNF) were compared quantitatively at the protein and mRNA levels by immunoblot
      and competitive RNA-polymerase chain reaction analyses. CYP1A1 mRNA levels in
      both organs increased sharply and were maximal at approximately 6 hr and returned
      to near basal levels by 12 hr after BNF treatment. In contrast, hepatic CYP1A2
      mRNA levels increased much more gradually. Small intestinal CYP1A2 mRNA
      concentrations were insufficient to support translation of detectable protein.
      Maximal levels of intestinal and hepatic CYP1A1 protein occurred between 12 and
      24 hr, and 24 and 48 hr, respectively, after BNF. Intestinal CYP1A1 protein was
      detectable earlier and for a shorter duration than hepatic CYP1A1. CYP1A1
      induction was first detected in crypt cells 3 hr before the appearance of
      activity in villous cells, and maximal levels of activity were reached in crypt
      cells 12 to 18 hr before maximal and 1.5-fold (per mg protein) higher responses
      in villous cells-induction thus occurs in both villous and crypt cells.
      Previously detected decreases in CYP1A1 inducibility from duodenum to ileum
      correlated with decreases in immunoblot determined-Ah receptor levels. Intestinal
      CYP1A1 induction does not involve the glucocorticoid receptor in contrast to
      hepatic induction. These studies have revealed several novel features of small
      intestinal CYP1A1 regulation.

PMID- 9010627
TI  - Disposition and metabolism of 2,6-dimethylbenzamide N-(5-methyl-3-isoxazolyl)
      (D2916) in male and female rats.
AB  - Disposition and metabolism of the new anticonvulsant 2,6-dimethylbenzamide N-(5
      methyl-3-isoxazolyl) (D2916) was studied in male and female rats after oral
      administration of 14C-labeled material. D2916 was well absorbed in both sexes and
      distributed to all tissues, with maximal drug concentrations found in elimination
      and metabolization organs, as well as in fatty tissues. Striking differences in
      pharmacokinetic parameters of total radioactivity were observed between males and
      females; females had higher brain concentrations and longer blood and tissue half
      lives. The study of blood, bile, urine, and brain metabolites showed that D2916
      follows two degradation pathways related to hydroxylation of methyl groups. Males
      prefer to hydroxylate one of the methyl groups of the phenyl ring, and females
      prefer to hydroxylate the methyl of the isoxazolyl ring forming the active
      metabolite D3187. These findings suggest a sex difference in the location of the
      hydroxylation of the D2916 molecule and can explain the longer anticonvulsant
      effect observed in the female rat that is related both to an orientation of the
      metabolism toward the formation of the active metabolite and to a better ability
      to this metabolite to cross the blood-brain barrier, compared with the unchanged
      drug.

PMID- 9010626
TI  - Nonenzymatic isomerization of 9-cis-retinoic acid catalyzed by sulfhydryl
      compounds.
AB  - Certain thiol-containing compounds catalyze, in a chemical reaction, the
      isomerization of 9-cis-retinoic acid to a mixture of all-trans-retinoic acid, 9
      cis-retinoic acid, 13-cis-retinoic acid, and 9,13-dicis-retinoic acid. In the
      presence of such catalysts, all-trans-retinoic acid gives rise to the same
      mixture. Reactions approaching equilibrium contain more all-trans-retinoic acid
      than either of the other isomers. Small molecules effective as catalysts are
      mercaptoethanol, L-cysteine methyl ester, glutathione, and N-acetyl-L-cysteine.
      Apoferritin (a thiol-containing protein), native microsomes, and, to a lesser
      extent, boiled microsomes catalyze the reaction. In intact cells, these
      interconversions also occur in a process inhibited by a sulfhydryl-specific
      reagent. The thiol-catalyzed isomerization of 9-cis-retinoic acid may be relevant
      in the biological activity of this compound.

PMID- 9010628
TI  - Pharmacokinetics and metabolism of the novel anticonvulsant agent N-(2,6
      dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) in rats and humans.
AB  - N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) belongs to a new
      series of experimental anticonvulsants related to lidocaine. This study was
      undertaken to understand the pharmacokinetics and metabolism of D2624 in rats and
      humans, with emphasis on the possible formation of 2,6-dimethylaniline (2,6-DMA).
      After oral administration of stable isotope-labeled parent drug to rats and GC/MS
      analysis of plasma samples, two metabolites were identified: D3017, which is the
      primary alcohol, and 2,6-DMA, formed by amide bond hydrolysis of either D2624 or
      D3017. In urine, three metabolites of D2624 were identified: namely D3017,2,6
      DMA, and D3270 (which is the carboxylic acid derivative of D3017). Based on
      plasma AUC analysis, D3017 and 2,6-DMA accounted for > 90% of the dose of D2624.
      After oral administration, D2624 was found to be well absorbed (93%), but
      underwent extensive first-pass metabolism in the rat, thus resulting in 5.3%
      bioavailability. Rat and human liver microsomal preparations were capable of
      metabolizing D2624 to D3017 and 2,6-DMA. The formation of D3017 was NADPH
      dependent, whereas 2,6-DMA formation was NADPH-independent and probably was
      catalyzed by amidase(s) enzymes. In a single-dose (25-225 mg) human volunteer
      study, the parent drug (D2624) was not detected in plasma at any dose, whereas
      2,6-DMA was detected only at the two highest doses (150 and 225 mg). D3017 was
      detected after all doses of parent drug, with approximate dose proportionality in
      AUC and a half-life of 1.3-2.2 hr. The metabolic behavior observed in humans
      suggests there is a marked species difference in the oxidative and hydrolytic
      pathways of D2624.

PMID- 9010629
TI  - Metabolites of nicotine in rat brain after peripheral nicotine administration.
      Cotinine, nornicotine, and norcotinine.
AB  - The time course of nicotine metabolite appearance in brain from 5 min-18 hr after
      subcutaneous administration of S-(-)-[3H-N-methyl]nicotine was determined.
      Results demonstrated that metabolite appearance in brain was greatest at 4 hr
      postadministration, whereas levels of nicotine were greatly diminished at this
      time point. For determination of N-demethylated metabolites, (+/-)-[2'
      14C]nicotine was administered subcutaneously to rats, and the presence of
      nicotine and nicotine metabolites in brain supernatant was determined 4 hr
      postadministration. Using high-performance liquid radiochromatographic analysis,
      nicotine and three nicotine metabolites (cotinine, nornicotine, and norcotinine)
      were identified in brain, together with a fourth minor, unidentified metabolite.
      After subcutaneous administration of S-(-)-[G-3H]cotinine, significant amounts of
      cotinine were found in brain over an 18-hr postadministration period; however, no
      cotinine metabolites were detected. Therefore, cotinine is able to pass the blood
      brain barrier and access the central nervous system, but is not biotransformed in
      brain. Thus, this is the first report of norcotinine as a central nervous system
      nicotine metabolite. Data indicate that norcotinine detected in brain after
      peripheral nicotine administration most likely originates from 5'-C-oxidation of
      brain nornicotine, rather than from N-demethylation of cotinine, as occurs
      peripherally. Because peripheral biotransformation of nicotine to nornicotine is
      a minor pathway, the relatively high levels of nornicotine found in brain after
      peripheral nicotine administration suggest that nornicotine is formed via
      oxidative N-demethylation of nicotine locally in brain. Nornicotine is
      pharmacologically active; thus, its presence in brain after peripheral nicotine
      administration indicates that nornicotine may contribute to the
      neuropharmacological effects of nicotine and tobacco use.

PMID- 9010630
TI  - Interaction of human serum albumin with the electrophilic metabolite 1-O
      gemfibrozil-beta-D-glucuronide.
AB  - Acyl glucuronides are electrophilic metabolites that are readily hydrolyzed,
      undergo intramolecular rearrangement, and bind covalently to endogenous proteins.
      Gemfibrozil is a fibrate lipid-lowering agent that is extensively metabolized to
      an acyl glucuronide conjugate in humans. The aims of this study were to examine
      the interactions of 1-O-gemfibrozil-beta-D-glucuronide with human serum albumin.
      The degradation of 1-O-gemfibrozil-beta-D-glucuronide (approximately 200 microM)
      was examined in vitro during incubations at 37 degrees C with phosphate buffer
      (pH 7.4 or 9.0), solutions of human serum albumin (pH 7.4), or fresh human plasma
      (pH 7.4). The effects of diazepam, oxyphenbutazone, and gemfibrozil on the
      degradation of 1-O-gemfibrozil-beta-D-glucuronide, and its reversible binding to
      albumin were also studied. A pilot in vivo study was performed on two patient
      volunteers administered 1 g/day p.o. gemfibrozil. 1-O-Gemfibrozil-beta-D
      glucuronide was unstable, with degradation half-lives in buffer of 4.1 hr and 44
      hr at pH 9.0 and 7.4, respectively; and 8.5 hr and 5.5 hr in pH 7.4 solutions of
      human serum albumin or fresh plasma, respectively. Degradation was dependent on
      pH and the presence of albumin, which seemed to accelerate the intramolecular
      rearrangement and hydrolysis of the conjugate. 1-O-Gemfibrozil-beta-D-glucuronide
      was highly reversibly bound to albumin, with a mean unbound fraction of 0.028,
      and its degradation seemed to be related to the degree of reversible binding.
      Hydrolysis and covalent binding were associated with the site II binding domain
      on albumin, because only diazepam inhibited these reactions. However,
      intramolecular rearrangement was increased when binding to the site I domain was
      inhibited. Covalent binding was also detected in vivo to human plasma proteins.
      The half-life of the gemfibrozil-protein adducts was 2.5-3 days. Albumin plays an
      important role in the disposition of acyl glucuronides by acting as: i) a
      transporter protein; ii) a potential catalyst for their degradation and,
      therefore, clearance; and iii) a target for covalent adduct formation.

PMID- 9010631
TI  - Effects of acute myocardial infarction on theophylline elimination in rats.
AB  - We investigated the effect of acute myocardial infarction (MI) on the hepatic
      clearance of theophylline in rats using the coronary artery ligation model. After
      48 hr of ligation, there were significant changes in left ventricular performance
      in the MI rats, compared with controls, as indicated by elevated left ventricular
      end-diastolic pressure, reduced mean arterial pressure, and reduced left
      ventricular systolic pressure (20 +/- 2 vs. 12 +/- 3 mm Hg, p < 0.01; 90 +/- 6
      vs. 101 +/- 6 mm Hg, p < 0.01; and 100 +/- 8 vs. 114 +/- 8 mm Hg, p < 0.01,
      respectively). Despite these changes, MI rats were able to maintain their cardiac
      output at rest (77.9 +/- 6.8 vs. 77.2 +/- 9.2 ml/min), and there was no change in
      mean central venous pressure (3 +/- 1 vs. 2 +/- 1 mm Hg). Although hepatic
      perfusion and oxygenation were preserved (17.3 +/- 2.2 vs. 18.7 +/- 3.3 ml/min
      and 127 +/- 27 vs. 125 +/- 19 mumol/min respectively), clearance of theophylline
      was reduced by 23% in the MI rats, compared with controls (0.86 +/- 0.20 vs. 1.12
      +/- 0.17 ml/min, p = 0.01). There was no significant correlation between
      theophylline clearance and the infarct size (r = -0.038, p > 0.05). These
      findings demonstrate that the elimination of theophylline is impaired after acute
      MI, independent of any changes in hepatic perfusion or oxygenation.

PMID- 9010632
TI  - Pharmacokinetics of DA-125, a new anthracycline, after intravenous administration
      to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats.
AB  - Pharmacokinetic parameters-including tissue distribution, biliary excretion, and
      urinary excretion of M1-M4-were compared after an intravenous administration of
      DA-125 (a new anthracycline derivative; 20 mg/kg body weight) to male
      spontaneously hypersensitive rats (SHRs) at 16 weeks (an animal model for human
      primary hypertension) and at 6 weeks (corresponding to the early phase of the
      development of hypertension, at which time blood pressure remains within the
      normotensive range) of age and their age-matched control Kyoto-Wistar rats, and
      male deoxycorticosterone acetate-salt-induced Sprague-Dawley rats (DOCA-salt
      rats, an animal model for human secondary hypertension) at 16 weeks of age and
      their age-matched control Sprague-Dawley rats. Mean plasma concentrations of both
      M2 and M4, and the resultant area under the plasma concentration-time curve from
      time 0 to last measured time [AUCT; M2 (68.9 vs. 29.3 micrograms-min/ml) and M4
      (53.4 vs. 33.4 micrograms-min/ml)], increased significantly in SHRs at 16 weeks
      of age, compared with their control rats. Similar results were also obtained from
      DOCA-salt rats at 16 weeks of age, compared with their control rats. However,
      values were not significantly different between SHRs at 6 weeks of age and their
      control rats. Previous data indicated that the significant increase in plasma
      concentrations and the resultant AUCT values of both M2 and M4 in SHRs at 16
      weeks of age were due to the hypertension state itself, and not to any hereditary
      characteristics of the SHRs. The significantly increased plasma concentrations
      and the resultant AUCT values of M2 in both SHRs and DOCA-salt rats at 16 weeks
      of age were due to the significantly decreased biliary excretion of M2 and
      possibly to the increased amount of aldo-keto reductase in the liver. However,
      the increase in the two aforementioned pharmacokinetic parameters in the case of
      M4 were possibly due solely to the increased amount of aldo-keto reductase in the
      liver.

PMID- 9010633
TI  - Identification of rat and human cytochrome P450 forms involved in the metabolism
      of the thromboxane A2 receptor antagonist (+)-S-145.
AB  - (+)-S-145 [5-(+)-(Z)-7-[(1R, 2S, 3S, 4S)-3-phenylsulfonylaminobicyclo[2.2.1]hept
      2-yl]-heptenoic acid] and its beta-oxidized metabolites [two [bisnor or dihydro
      (DH)-bisnor] or four (tetranor) carbon-shortened products at the carboxyl side
      chain] are hydroxylated at the C-5 or C-6 position of the bicyclo ring by
      microsomal monooxygenases. We investigated the oxidative metabolism of (+)-S-145
      and its beta-oxidized metabolites with liver microsomes from rats and humans to
      identify which cytochrome P450 (P450) forms are involved in these reactions. In
      rats, phenobarbital or dexamethasone treatment significantly increased 5- and 6
      hydroxylation activities toward (+)-S-145 and its beta-oxidized metabolites,
      suggesting the involvement of P4503A forms. Immunoinhibition studies suggested
      that P4503A2 was mainly responsible for the 5-hydroxylation of (+)-S-145, bisnor,
      and DH-bisnor and the 6-hydroxylation of bisnor and tetranor. Furthermore,
      P4502C6, a phenobarbital-inducible 2C form in the rat, was involved in the 6
      hydroxylation of (+)-S-145, bisnor, and DH-bisnor. P4502C11, the major
      constitutive form (male rats), was partly involved in the 5-hydroxylation of DH
      bisnor and the 6-hydroxylation of bisnor and DH-bisnor. Reconstitution studies
      with purified human enzymes and immunoinhibition studies suggest that P4503A4 is
      primarily involved in the 5-hydroxylation of (+)-S-145 and bisnor and the 6
      hydroxylation of tetranor; P4502C9/10 mainly catalyzed the 5-hydroxylation of
      tetranor and the 6-hydroxylation of (+)-S-145. Results of the present study
      indicated that the same subfamily P450 forms are responsible for the oxidative
      metabolism of (+)-S-145 in rats and humans. P4503A enzymes were shown to be
      involved in the formation of 6-hydroxy tetranor, the main metabolite of S-1452 in
      vivo.

PMID- 9010634
TI  - Disposition and biotransformation of the antipsychotic agent olanzapine in
      humans.
AB  - Disposition and biotransformation of the new antipsychotic agent olanzapine (OLZ)
      were studied in six male healthy volunteers after a single oral dose of 12.5 mg
      containing 100 microCi of [14C]OLZ. Biological fluids were analyzed for total
      radioactivity, the parent compound (GC/MS), and metabolites (electrospray LC/MS
      and LC/MS/MS). Mean radiocarbon recovery was approximately 87%, with 30%
      appearing in the faces and 57% excreted in the urine. Approximately half of the
      radiocarbon was excreted within 3 days, whereas > 70% of the dose was recovered
      within 7 days of dosing. Circulating radio-activity was mostly restricted to the
      plasma compartment of blood. Mean peak plasma concentration of OLZ was 11 ng/ml,
      whereas that of radioactivity was 39 ng eq/ml. Mean plasma terminal elimination
      half-lives were 27 and 59 hr, respectively, for OLZ and total radioactivity. With
      the help of NMR and MS data, a major metabolite of OLZ in humans was
      characterized as a novel tertiary N-glucuronide in which the glucuronic acid
      moiety is attached to the nitrogen at position 10 of the benzodiazepine ring.
      Another N-glucuronide was detected in urine and identified as the quaternary N
      linked 4'-N-glucuronide. Oxidative metabolism on the allylic methyl group
      resulted in 2-hydroxymethyl and 2-carboxylic acid derivatives of OLZ. The methyl
      piperazine moiety was also subject to oxidative attack, giving rise to the N
      oxide and N-deemethyl metabolites. Other metabolites, including the N-deemethyl-2
      carboxy derivative, resulted from metabolic reactions at both the 4' nitrogen and
      2-methyl groups. The 10-N-glucuronide and OLZ were the two most abundant urinary
      components, accounting for approximately 13% and 7% of the dose, respectively. In
      fecal extracts, the only significant radioactive HPLC peaks were due to 10-N
      glucuronide and OLZ representing, respectively, approximately 8% and 2% of the
      administered dose. Semiquantitative data obtained from plasma samples from
      subjects given [14C]OLZ suggest that the main circulating metabolite is 10-N
      glucuronide. Thus, OLZ was extensively metabolized in humans via N
      glucuronidation, allylic hydroxylation, N-oxidation, N-dealkylation and a
      combination thereof. The 10-N-glucuronidation pathway was the most important
      pathway both in terms of contribution to drug-related circulating species and as
      an excretory product in feces and urine.

PMID- 9010635
TI  - Interspecies variability of TNP-470 metabolism, using primary monkey, rat, and
      dog cultured hepatocytes.
AB  - The biotransformation of TNP-470 [O-(chloroacetylcarbamoyl)fumagillol; AGM 1470],
      a potent in vitro inhibitor of angiogenesis, was investigated in primary cultured
      hepatocytes isolated from different species, including monkey, dog, and rat, as
      well as in microsomal fractions of various monkey tissues. Previous metabolic
      studies by our group using human hepatocytes in primary culture demonstrated that
      TNP-470 was primarily metabolized to M-IV through an ester cleavage, with
      subsequent conversion of M-IV to M-II by microsomal epoxide hydrolase. Additional
      studies using monkey liver microsomes demonstrated that M-II was then
      glucuronidated by uridine-5'-diphosphoglucuronyl transferase, leading to the
      formation of M-III. Three other, as yet unidentified, metabolites, labeled M-I, M
      V, and M-VI, were also detected. Similarly to findings in human hepatocytes, the
      predominant extracellular metabolite was M-II in all species studied. Minor
      interspecies variability was observed in the total amount of drug biotransformed
      by hepatocytes, but some variability was detected in the metabolic pattern of TNP
      470 in monkey hepatocytes, compared with rat or dog hepatocytes. In monkey
      hepatocytes, as previously observed in human cells, TNP-470 was metabolized to
      six derivatives, labeled M-I, M-II, M-III, M-IV, M-V, and M-VI, whereas the
      latter metabolite was not observed in dog or rat extracellular medium.
      Extrahepatic metabolism of TNP-470 was also studied using monkey intestine,
      kidney, and lung microsomes, which demonstrated that, under these experimental
      conditions, TNP-470 was extensively metabolized to four derivatives, i.e. M-I, M
      II, M-III, and M-IV, with M-III being detected only in liver samples. These
      studies suggest that the metabolism of TNP-470 in monkeys appears to be most
      closely related to that observed in humans. Although the individual quantitative
      metabolic profiles were quite different in various animal species, only one
      metabolite, namely M-VI, was not detected in either dog or rat hepatocytes in
      vitro.

PMID- 9010636
TI  - Disposition and metabolism of finasteride in dogs.
AB  - Finasteride (FIN) is a potent 5 alpha-reductase inhibitor that has shown clinical
      success in treating men with benign prostatic hyperplasia. In the study of
      biological effects and metabolism of FIN in animals, the dog serves as the
      primary modality. This study was conducted to determine the pharmacokinetics and
      fate of FIN after oral administration of single doses of [14C]FIN to dogs at 10
      and 80 mg/kg (N = 2 and 3, respectively), and also after intravenous infusion at
      5 mg/kg (N = 2). Plasma, urine, and feces were analyzed for total 14C content.
      Parent drug and metabolites in plasma and excreta were measured by
      HPLC/UV/radioassay and identified by NMR spectroscopy and MS, FIN was subject to
      extensive biotransformation before excretion. Structures were determined for the
      major metabolites in plasma, urine, and feces. The primary metabolic events for
      FIN were hydroxylation of the t-butyl side chain to give hydroxymethyl-FIN
      (metabolite I), which is oxidized further to form the carboxylic acid derivative
      (metabolite IV), and hydroxylation at positions B alpha and 15. Terminal half
      life of FIN after the intravenous dose was 3.4 hr. Plasma clearance and volume of
      distribution at steady-state were 4.8 ml/min/kg and 1.1 liter/kg. Dogs showed
      rapid absorption after oral administration of the low dose, with Cmax reached in
      the 1-2 hr, bioavailability was estimated to be > 90%. After either dosing route,
      45% of the plasma radioactivity (as represented by AUC) was parent drug, 43% was
      metabolite I, and 1% was metabolite IV. After oral administration, the 80 mg/kg
      dose was absorbed slowly, with the highest levels of radioactivity in plasma
      reached in 4-30 hr. Average Cmax value for FIN and metabolite I increased in a
      dose-related, but nonproportional, manner. Compared with the 10 mg/kg dose, it
      seems the higher dose was reasonably well-absorbed, as indicated by the nearly
      proportional increase of AUC values of total radioactivity and FIN. Composition
      of plasma metabolites observed at the 80 mg/kg dose level was similar to that
      observed previously for the low dose, suggesting that an increase in plasma
      exposure was effected in dogs receiving FIN at 80 mg/kg in toxicity studies. Most
      of the administered radioactivity was recovered in feces after all doses. Little
      of the intravenous and low oral doses, but > 50% of the 80 mg/kg oral dose, was
      excreted as intact FIN, suggesting that metabolism might have been saturated at
      the high dose.

PMID- 9010638
TI  - Substituent elimination from p-substituted phenols by cytochrome P450. ipso
      Substitution by the oxygen atom of the active species.
AB  - When various p-substituted phenols (substituent = NO2, CN, CH2OH, COCH3, COPh,
      COOH, F, Cl, and Br) were incubated with rat liver microsomes, the substituent
      was eliminated to produce hydroquinone, and the reaction was inhibited by CO and
      a cytochrome P450-specific inhibitor. In the case of p-cresol (substituent =
      CH3), p-toluquinol was formed instead of hydroquinone. Experiments using 18O2
      proved that the elimination is accompanied with ipso-substitution by the oxygen
      atom of the active species in cytochrome P450. These results are similar to those
      in a cytochrome P450. These results are similar to those in a cytochrome P450
      chemical model system (Ohe, T., et al., Tetrahedron Lett. 42, 7681-7684, 1995),
      implying that the model is a good mimic of cytochrome P450. Substrates that lack
      a hydroxy group, namely p-substituted toluenes, did not undergo the reaction,
      thus indicating that a hydroxy group at the p-position to the eliminated
      substituent is necessary for this pathway. This is the same as the result
      obtained with the cytochrome P450 model. Finally, to elucidate how the
      substituent is eliminated, we attempted to detect the product derived from the
      eliminated group with several substrates. Results indicated that the mechanism of
      the substituent elimination can be divided into two types: the substituent is
      eliminated as an anion or as a cation.

PMID- 9010637
TI  - Identification of cytochromes P450 involved in the human liver microsomal
      metabolism of the thromboxane A2 inhibitor seratrodast (ABT-001).
AB  - Seratrodast (ABT-001, AA-2414) undergoes cytochrome P450 (CYP)-dependent
      metabolism to a major (5-methylhydroxy seratrodast; 5-HOS) and a minor 4'-hydroxy
      seratrodast metabolite in human liver microsomes. The mean apparent K(m) and Vmax
      for the formation of 5-HOS were 15.5 microM and 589.0 pmol 5-HOS formed/mg
      protein/min, respectively. Chemical inhibition using isoform-selective CYP
      inhibitors, correlation of 5-HOS formation with several isoform-specific CYP
      activities in a panel of liver microsomes, metabolism by microsomes derived from
      CYP cDNA-expressed B-lymphoblastoid cells, and immunoinhibition by isoform
      specific anti-CYP antibodies indicated that 5-HOS formation is catalyzed by CYP3A
      and CYP2C9/10, with a minor contribution from CYP2C8 and CYP2C19. At clinically
      relevant concentrations, seratrodast was found to inhibit tolbutamide
      methylhydroxylation (IC50 = 60 microM), (S)-mephenytoin 4'-hydroxylation (IC50 =
      50 microM), and coumarin 7-hydroxylation (IC60 = 95 microM), indicating the
      potential for significant clinical interactions. The inducers of CYP3A and/or
      CYP2C9 (e.g. rifampicin and phenytoin) are likely to alter the disposition of
      seratrodast.

PMID- 9010639
TI  - In vitro and in vivo disposition of 2,2-dimethyl-N-(2,4,6
      trimethoxyphenyl)dodecanamide (CI-976). Identification of a novel five-carbon
      cleavage metabolite in rats.
AB  - The metabolism of CI-976, a potent inhibitor of liver and intestinal acyl
      coenzyme A:cholesterol acyltransferase, was investigated in isolated rat
      hepatocytes and Wistar rats after oral administration. The major metabolite
      observed both in vitro and in vivo was identified as the 6-carbon, chain
      shortened 5,5-dimethyl-6-oxo-[(2,4,6-trimethoxyphenyl)amino]hexanoic acid (M-4).
      M-4 was determined to be formed from the omega-carboxylic acid 11,11-dimethyl-12
      oxo-12-[(2,4,6-trimethoxyphenyl)amino]dodecanoic acid (M-1) via the 2- and 4
      carbon, chain-shortened intermediate metabolites [9,9-dimethyl-10-oxo-10-[(2,4,6
      trimethoxyphenyl)amino]decanoic acid (M-2) and 7,7-dimethyl-8-oxo-8-[(2,4,6
      trimethoxyphenyl)amino]octanoic acid (M-3)], respectively. M-1 was, in turn,
      determined to be derived from omega-hydroxy CI-976. A minor metabolite,
      identified in vitro and in vivo, was a novel 5-carbon, chain-shortened
      derivative, 6,6-dimethyl-7-oxo-7-[(2,4,6-trimethoxyphenyl)amino]heptanoic acid (M
      5). M-5 was shown not to be formed from either M-1 or the omega-hydroxy
      derivative. Separate incubation of CI-976 (omega-oxidation and beta-oxidation
      pathways) and M-1 (beta-oxidation only) indicated a potential gender difference
      in the omega-oxidation of CI-976. Both the omega-oxidation and beta-oxidation
      pathways were enhanced by clofibrate and phenobarbital induction, and CI-976
      metabolism was completely inhibited when coincubated with SKF525A pointing to
      cytochrome P450-mediated metabolism, presumably CYP4A. Etomoxir and L-carnitine
      had minor effects on the beta-oxidation of M-1, indicating beta-oxidation occurs
      predominately within peroxisomes.

PMID- 9010640
TI  - Role of viral infections in the induction of adverse drug reactions.
AB  - A spectrum of adverse drug reactions that are caused by the combined action of
      drugs and viruses has been described: ampicillin rash in acute infectious
      mononucleosis; Reye's syndrome; hypersensitivity reactions to sulphonamides in
      patients with HIV infection; drug-induced agranulocytosis; paracetamol
      (acetaminophen) hepatotoxicity; aspirin (acetylsalicyclic acid)-induced asthma;
      Epstein-Barr virus-associated lymphoma and methotrexate; and AIDS-related
      Kaposi's sarcoma and nitrite use. Changes in pharmacokinetics have been reported
      for: caffeine, sulfamethoxazole and fluconazole in patients with HIV infection;
      theophylline, following influenza and influenza vaccination; and recently,
      dipyrone metabolites in carriers of the hepatitis B virus. In addition increased
      drug- and drug metabolite-related toxicity has been observed in virally infected
      cells. Pathogenetic mechanisms for the interaction between drugs and viruses are
      varied, and include biological mechanisms (often immunological) and changes in
      drug metabolism. The combined effects of chemical and biological exposure provide
      a unique model for the study of disease induction.

PMID- 9010642
TI  - A risk-benefit assessment of corticosteroids in the management of croup.
AB  - Croup is an acute clinical syndrome of childhood characterised by a barking
      cough, hoarse voice, stridor and a variable degree of respiratory distress. A
      meta-analysis and subsequent controlled trials clearly demonstrate that
      corticosteroids are efficacious in the management of croup, with their benefits
      conclusively outweighing their risks. In mild to moderate cases of croup either
      systemic or nebulised corticosteroids decrease symptoms and need for
      hospitalisation. Most reports use IM dexamethasone 0.6 mg/kg, although it is
      likely that dexamethasone 0.15 mg/kg has a similar effect. In controlled studies
      nebulised budesonide 2 mg is superior to placebo, and appears to have equivalent
      efficacy to oral dexamethasone. The risk of a single or short course of systemic
      corticosteroids are minimal, the only potential significant adverse effect being
      increased risk of severe varicella infection. Short courses of nebulised
      budesonide have no major adverse effects, and thus are likely to cause fewer
      adverse effects than systemic corticosteroids, although this is as yet unproven.
      On the body of data published to date, either oral dexamethasone 0.15 mg/kg or
      nebulised budesonide 2 mg are effective for mild to moderate croup. In severe
      croup requiring intubation, oral prednisolone 1 mg/kg every 12 hours decreases
      the duration of intubation and the need for re intubation. Unless there are clear
      contraindications, corticosteroids are the treatment of choice in mild, moderate
      and severe croup.

PMID- 9010643
TI  - A risk-benefit assessment of losartan potassium in the treatment of hypertension.
AB  - Losartan potassium is the first of a new class of orally active antihypertensive
      drugs which antagonise the action of angiotensin (AT) II at the AT1 receptor
      subtype. Losartan potassium is converted by the liver to the active metabolite E
      3174, which is a more potent antagonist at the AT1 receptor. E-3174 is
      responsible for most of the pharmacological effects of losartan potassium, and
      its long half-life contributes to the extended duration of action of the drug.
      Losartan potassium is effective as a once-daily antihypertensive agent. In mild
      to moderate hypertension, losartan potassium has similar efficacy to enalapril,
      atenolol and felodipine extended release. When losartan potassium is combined
      with hydrochlorothiazide there is a further reduction in blood pressure. Losartan
      potassium is well tolerated in mild, moderate and severe essential hypertension,
      with dizziness being reported as the only drug-related adverse effect. The
      overall rate of patient withdrawal from therapy due to adverse experiences with
      losartan potassium is lower (2.3%) than that of placebo (3.7%). First-dose
      hypotension is uncommon, perhaps due to the slower onset of action of the drug,
      and cough does not appear to be a significant problem. A number of areas
      concerning the safety and efficacy of losartan potassium remain to be clarified.
      In particular, long term tolerability studies are needed; cough only became
      apparent as an adverse effect of ACE inhibitors after 3 to 4 years of use.
      Postmarketing surveillance has shown that angioedema, a rare but life-threatening
      adverse effect of ACE inhibitors, also occurs with losartan potassium. Further
      data are needed on the use of losartan potassium in patients with renal
      impairment before accepting the recommendation that dosage adjustment is not
      necessary. The pharmacokinetics and pharmacodynamics of losartan potassium in
      patients with hepatic disease also require further investigation. Losartan
      potassium increases uric acid secretion and lowers plasma uric acid levels, which
      may be of benefit when losartan potassium is combined with a thiazide diuretic,
      but which may otherwise lead to uric acid stone formation and possibly to
      nephropathy. Simple control of blood pressure is no longer an adequate goal in
      the management of hypertension. Any new antihypertensive agent should also reduce
      cardiovascular events, prevent or cause regression of end-organ damage such as
      left ventricular hypertrophy, atherosclerosis and renal failure, and should not
      impair quality of life. Such data on losartan potassium are not currently
      available. Losartan potassium is likely to be used in patients who are intolerant
      of ACE inhibitors, but its future in the management of hypertension will depend
      on long term tolerability studies and data on its effects beyond simple blood
      pressure control.

PMID- 9010641
TI  - Clinical applications of commonly used contemporary antidotes. A US perspective.
AB  - Poisonings are a common problem. In 1995, over 2 million exposures were reported
      to American poison information centres alone. The majority of poisoning exposures
      can be treated without major therapeutic intervention. If therapy is indicated,
      it is usually in the form of gastrointestinal decontamination with activated
      charcoal, to prevent absorption of the toxin and the subsequent toxicity that may
      occur. In a limited number of cases, more aggressive life-support measures may be
      necessary to treat the adverse effects of poisons. Occasionally, that
      intervention may include the use of pharmacological antagonists, more commonly
      referred to as antidotes. According to the American Association of Poison Control
      Centers, the most commonly used antidotes are acetylcysteine, naloxone, atropine,
      deferoxamine (desferrioxamine) and antivenins. Overall, 17 antidotes account for
      99% of all antidote use and those agents are reviewed in this article. With the
      exception of naloxone, most antidotes have pharmacological effects that are
      independent of their inherent antidotal properties. Therefore, antidotes should
      be used judiciously because their pharmacological properties may exacerbate pre
      existing toxicity and only in rare circumstances are they used prophylactically.
      Some antidotes, such as digoxin-specific antigen binding fragments (digoxin
      immune Fab), are very expensive, and both the risk: benefit ratio and the
      associated cost should be considered before the antidote is administered. The
      principle aims are to "treat the patient, not the poison' and to do no harm to
      the patient. Antidotes should be used only when they are indicated and may help a
      patient.

PMID- 9010645
TI  - Gastric toxicity of antiplatelet therapy with low-dose aspirin.
AB  - Low-dose aspirin is widely employed as antiplatelet therapy for cardiovascular
      disorders. However, even in the dosages usually employed for that purpose (75 to
      325 mg daily), the drug maintains its ability to damage the gastric mucosa by
      inducing bleeding ulcers and/or erosions. Pharmacological protection is therefore
      necessary. Specific long term studies with histamine H2 receptor antagonists or
      sucralfate are lacking, but data from trials on the prevention of gastric damage
      by other nonsteroidal anti-inflammatory drugs (NSAIDs) are discouraging. Recent
      preliminary data suggest that misoprostol, in keeping with its ability to protect
      both gastric and duodenal mucosa from long term NSAID treatment, seems to be
      effective also against long term low-dose aspirin therapy in this setting.

PMID- 9010644
TI  - A risk-benefit assessment of tacrine in the treatment of Alzheimer's disease.
AB  - Tacrine, the first drug specifically approved for Alzheimer's disease, produces
      symptomatic improvement. The theoretical rationale behind treating Alzheimer's
      disease with tacrine is based on central cholinergic depletion. Tacrine is
      centrally acting, uncompetitive reversible inhibitor of acetylcholinesterase and
      butyrylcholinesterase. Multiple clinical trials support the effectiveness of
      tacrine in Alzheimer's disease. High dosages of tacrine are required for
      efficacy, with the potential for hepatic and mild gastrointestinal adverse
      effects. However, the benefits of tacrine currently outweigh its risks, and a
      trial of the drug should be offered to patients. As clinical experience with
      tacrine increases, the long term risk-benefit equation may be refined.

PMID- 9010646
TI  - NSAID-induced gastrointestinal damage. Epidemiology, risk and prevention, with an
      evaluation of the role of misoprostol. An Asia-Pacific perspective and consensus.
AB  - The problem of nonsteroidal anti-inflammatory drug (NSAID)-induced
      gastrointestinal toxicity was reviewed by members of the Asia Pacific League of
      Associations for Rheumatology (APLAR) in a consensus conference in September
      1992. This paper by the participants presents the consensus conclusions
      incorporating knowledge from recent publications. There had been a high level of
      concern that much of the toxicity had resulted from extensive and indiscriminate
      prescribing of NSAIDs. The implementation of evidence-based guidelines was
      considered likely to be able to effect a substantial reduction in toxicity
      without significant loss of overall therapeutic benefit. The evidence from which
      such guidelines could be developed is critically appraised.

PMID- 9010647
TI  - The non-antiemetic uses of serotonin 5-HT3 receptor antagonists. Clinical
      pharmacology and therapeutic applications.
AB  - The discovery of multiple subtypes of the serotonin 5-HT receptor has generated
      enormous interest over the past few years. Possibly the most exciting, in terms
      of psychiatric clinical practice, appeared to be the 5-HT3 receptor. Early animal
      studies suggested that the 5-HT3 receptor antagonists, in addition to their well
      recognised antiemetic use, might be clinically useful in a number of areas. These
      included anxiety disorders, psychotic disorders, drug and alcohol abuse
      disorders, depressive disorders, cognitive disorders, the treatment of pain and
      the treatment of irritable bowel syndrome. With the exception of antiemetic
      actions, this review examines these potential therapeutic areas carefully, paying
      particular attention not only to the animal literature, but to the clinical
      studies which have resulted from these initial findings. Unfortunately, studies
      in many of these therapeutic areas have not lived up to their initial promise.
      Indeed, no clinical studies have yet clearly demonstrated the usefulness of 5-HT3
      receptor antagonists in the treatment of CNS disorders. Nonetheless, in view of
      the absence of published results from double-blind, placebo-controlled studies in
      many of these therapeutic areas, further research would be useful in confirming
      the effectiveness, or otherwise, of this group of compounds.

PMID- 9010649
TI  - A practical guide to the use of interferons in the management of hepatitis virus
      infections.
AB  - The recommended interferon dosage for patients with chronic hepatitis and typical
      hepatitis B virus (HBV) infection is 10 MU 3 times weekly for 4 to 6 months; with
      such a regimen sustained alanine aminotransferase (ALT) normalisation, liver
      histology improvement, clearance of HBV DNA and seroconversion from hepatitis B e
      antigen (HBeAg) to anti-HBe are obtained in about 40% of treated patients.
      Patients with elevated disease activity (high ALT values, active chronic
      hepatitis, low HBV DNA levels) tend to respond better to therapy; Oriental
      patients and immunocompromised patients are not ideal candidates for interferon.
      Patients with chronic hepatitis B and the HBeAg-negative variant should be given
      intermediate dosages (6 to 9 MU thrice weekly) of interferon for prolonged
      periods (12 months); however, even with this approach, the relapse rate is high
      (> 60%) during the follow-up. In chronic hepatitis D virus (HDV) infection,
      therapy with 9 to 10 MU of interferon 3 times weekly for 12 months induces a
      transient remission in disease (ALT normalisation, HDV RNA clearance) in more
      than 50% of treated patients, but a sustained response is found in less than 20%
      of patients. In such disease, baseline predictive factors of long term response
      are still unknown. In chronic hepatitis C, treatment with 3 to 5 MU of interferon
      given 3 times weekly for 6 to 12 months induces a sustained remission in no more
      than 30% of treated patients. Probable predictive factors of long term response
      are: low viraemia, genotype other than 1, absence of cirrhosis, low intrahepatic
      iron content, low nucleotide diversity of the envelope 2 gene of the hepatitis C
      virus. Prolonged (> 12 months) therapeutic courses seem to enhance the sustained
      response rate; in nonresponders/relapsers, combined therapy (interferon plus
      indomethacin, interferon plus ketoprofen, interferon plus ribavirin) is promising
      but randomised controlled trials are needed in order to establish the real
      efficacy and safety of such therapeutic regimens.

PMID- 9010648
TI  - Drug treatment of HIV-related opportunistic infections.
AB  - The AIDS epidemic has led to the emergence of several disease entities which in
      the pre-AIDS era were rare or seemingly innocuous. Experience of treating these
      diseases varies. In some instances, such as Pneumocystis carinii pneumonia, there
      is an abundance of published literature to direct our course of action. However,
      for many of these newly recognised diseases our treatment experience is limited.
      Furthermore, in many instances, well controlled trials evaluating treatment
      modalities in the AIDS population are lacking. We have identified 13 disease
      entities (P. carinii pneumonia, toxoplasmosis, cryptococcosis, histoplasmosis,
      Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus,
      coccidioidomycosis, isosporiasis, candidosis, Kaposi's sarcoma, herpes simplex
      virus, and varicella zoster virus) and have reviewed the current literature with
      regard to their treatment.

PMID- 9010650
TI  - Optimum treatment of streptococcal pharyngitis.
AB  - Streptococcal pharyngitis is a common infection in children and adolescents. The
      great majority of these infections are caused by group A beta-haemolytic
      streptococci. Although the use of penicillins for group A beta-haemolytic
      streptococcal pharyngitis has reduced the incidence of rheumatic fever, in the
      past decade several studies of pharyngitis treatment have reported penicillin
      failure. It has also been suggested that in comparison with the penicillins the
      cephalosporins are associated with a lower rate of clinical failure.
      Cephalosporins have drawbacks in cost, administration frequency or adverse effect
      profile. Moreover, there is the theoretical risk of cross-antigenicity to
      cephalosporins in penicillin-allergic patients. Erythromycin is a traditional
      alternative to penicillins, especially in penicillin-allergic patients, for the
      treatment of tonsillopharyngitis. However, increased resistance as well as
      failure rates as high as 24.7% have been reported for erythromycin in the
      treatment of pharyngitis. Therefore oral penicillins, and alternatively oral
      cephalosporins, should be considered first-line agents for the treatment of
      culture-confirmed group A beta-haemolytic streptococcal tonsillopharyngitis.
      Cephalosporins are useful especially for the treatment of recurrent streptococcal
      tonsillopharyngitis.

PMID- 9010651
TI  - Diacerein.
AB  - Rhein, the active metabolite of diacerein, inhibits interleukin-1 activity.
      Consequently, collagenase production in articular cartilage is reduced. Rhein
      dose-dependently inhibits superoxide anion production, chemotaxis and phagocytic
      activity of neutrophils, and macrophage migration and phagocytosis. Articular
      cartilage damage is reduced by diacerein in animal models of osteoarthritis.
      Diacerein does not alter renal or platelet cyclooxygenase activity and may
      therefore be tolerated by patients with prostaglandin-dependent renal function.
      In clinical trials of < or = 6 months' duration, oral diacerein 50mg twice daily
      was associated with improvement in 57 to 85% of patients with osteoarthritis.
      Pain scores and measures of joint function were generally reduced compared with
      baseline and placebo. Diacerein had similar efficacy to NSAIDs, but a slower
      onset of action, in comparative trials of < or = 2 months' duration conducted in
      patients with osteoarthritis. The predominant adverse effects of diacerein are
      diarrhoea and related disorders.

PMID- 9010652
TI  - Transdermal fentanyl. A review of its pharmacological properties and therapeutic
      efficacy in pain control.
AB  - Fentanyl is a synthetic opioid with short-acting analgesic activity after
      intravenous or subcutaneous administration. The low molecular weight, high
      potency and lipid solubility of fentanyl make it suitable for delivery via the
      transdermal therapeutic system (TTS). These systems are designed to release the
      drug into the skin at a constant rate ranging from 25 to 100 micrograms/h,
      multiple systems can be applied to achieve higher delivery rates. Initially, much
      of the clinical experience with fentanyl TTS was obtained in patients with acute
      postoperative pain. However, because of the increased risk of respiratory
      complications, fentanyl TTS is contraindicated in this setting. Fentanyl TTS is
      recommended for use in chronic cancer pain. Moreover, in 11 countries worldwide
      including the US, its use is not restricted to chronic cancer pain; the drug is
      also available for treatment of general chronic pain, including that of
      nonmalignant origin. At the start of fentanyl TTS treatment, depot accumulation
      of the drug within skin tissue results in a significant delay (17 to 48 hours)
      before maximum plasma concentration is achieved. Approximately half of the cancer
      patients converted to transdermal fentanyl from other opioid agents required
      increased dosages after initial application of the patch. However, concomitant
      use of short-acting morphine maintained pain relief during the titration period,
      and the use of such supplementary medication decreased with the duration of
      fentanyl TTS treatment. In patients with chronic cancer pain, changes in visual
      analogue scale (VAS) pain scores ranged from a 10% increase (worse pain) to > 50%
      decrease (less pain) during transdermal fentanyl therapy compared with previous
      opioid treatment. In addition, patient preference for fentanyl TTS was indicated
      by the number of patient requests (up to 95%) for continued use of the drug at
      the end of the study. Although fentanyl TTS is contraindicated in patients
      postoperatively, the efficacy of fentanyl via the transdermal route was
      investigated in this patient group. Supplementary patient controlled analgesia
      was significantly reduced in patients who received fentanyl TTS 75 micrograms/h
      compared with placebo, although this was not apparent until > or = 12 hours after
      application. Data evaluating pain relief, which was assessed by VAS pain scores,
      were inconclusive. Preliminary data, although from relatively small numbers of
      patients, indicate that transdermal fentanyl may be useful in the management of
      chronic non-malignant pain. Indeed, some patients whose pain was previously
      uncontrolled became completely pain free. The most frequently occurring adverse
      events during fentanyl TTS therapy (as with other opioid agents) included
      vomiting, nausea and constipation, although vomiting and nausea were not clearly
      associated with the drug. The most serious adverse event was hypoventilation,
      which occurred more frequently in postoperative (4%) than in cancer patients
      (2%). In surgical patients, fentanyl-associated respiratory events (reduced
      respiratory rate and apnoea) generally occurred within 24 hours of patch
      application; however, there were isolated reports of late onset (> or = 36 hours
      postsurgery) fentanyl-associated respiratory depression. In cancer patients, the
      incidence of constipation was reduced by up to two-thirds after switching from
      oral morphine to transdermal fentanyl. Transient skin irritation associated with
      the plastic patch or the adhesive, rather than the drug, was reported in a
      maximum 3% of patients. In summary, transdermal fentanyl is a useful alternative
      to other opioid agents, which are also recommended on the third step of the WHO
      analgesic ladder, in the management of chronic malignant pain. Preliminary data
      indicate that it may be useful in the management of chronic nonmalignant pain.
      The advantages offered by fentanyl TTS over traditional methods of chronic pain
      control include its ease of administration, less constipation and the 3-

PMID- 9010654
TI  - XXVI Berzelius Symposium on Mental and Psychosocial Adaptation in Children--a
      longitudinal and prospective approach. Proceedings.

PMID- 9010655
TI  - Connections between child and adult psychopathology.

PMID- 9010656
TI  - Modeling development: using covariance structure models in longitudinal research.

PMID- 9010657
TI  - Retrospective and prospective design and data.

PMID- 9010658
TI  - Interactionism and the person approach in developmental psychology.

PMID- 9010659
TI  - Analyzing longitudinal categorical data: sources of uncertainty and sample
      methods.

PMID- 9010660
TI  - Measurement and data quality in longitudinal research.
AB  - The importance of paying attention to scale levels is emphasized and it is
      pointed out that Steven's hierarchy of ratio, interval, ordinal, and nominal
      scales is too narrow; other important scale properties have to be considered. For
      instance, sometimes a carefully constructed variable on a nominal scale contains
      more information than a variable at a higher scale level. Direct versus indirect
      measurement and relative versus absolute measurement are also discussed and the
      effects of errors of measurement on the results are considered. It is not
      infrequent in a longitudinal setting to disregard sampling considerations, which
      can be very unfortunate. Such considerations, as well as the use of modern
      sampling theory, can considerably enhance the quality of a longitudinal study.
      Finally, a number of conclusions and recommendations are given for the carrying
      out of longitudinal research in relation to measurement issues.

PMID- 9010653
TI  - Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties
      and therapeutic use in pain management.
AB  - Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with strong analgesic
      activity. The analgesic efficacy of ketorolac has been extensively evaluated in
      the postoperative setting, in both hospital inpatients and outpatients, and in
      patients with various other acute pain states. After major abdominal, orthopaedic
      or gynaecological surgery or ambulatory laparoscopic or gynaecological
      procedures, ketorolac provides relief from mild to severe pain in the majority of
      patients and has similar analgesic efficacy to that of standard dosages of
      morphine and pethidine (meperidine) as well as less frequently used opioids and
      other NSAIDs. The analgesic effect of ketorolac may be slightly delayed but often
      persists for longer than that of opioids. Combined therapy with ketorolac and an
      opioid results in a 25 to 50% reduction in opioid requirements, and in some
      patients this is accompanied by a concomitant decrease in opioid-induced adverse
      events, more rapid return to normal gastrointestinal function and shorter stay in
      hospital. In children undergoing myringotomy, hernia repair, tonsillectomy, or
      other surgery associated with mild to moderate pain, ketorolac provides
      comparable analgesia to morphine, pethidine or paracetamol (acetaminophen). In
      the emergency department, ketorolac attenuates moderate to severe pain in
      patients with renal colic, migraine headache, musculoskeletal pain or sickle cell
      crisis and is usually as effective as frequently used opioids, such as morphine
      and pethidine, and other NSAIDs and analgesics. Subcutaneous administration of
      ketorolac reduces pain in patients with cancer and seems particularly beneficial
      in pain resulting from bone metastases. The acquisition cost of ketorolac is
      greater than that of morphine or pethidine; however, in a small number of
      studies, the higher cost of ketorolac was offset when treatment with ketorolac
      resulted in a reduced hospital stay compared with alternative opioid therapy. The
      tolerability profile of ketorolac parallels that of other NSAIDs; most clinically
      important adverse events affect the gastrointestinal tract and/or renal or
      haematological function. The incidence of serious or fatal adverse events
      reported with ketorolac has decreased since revision of dosage guidelines.
      Results from a large retrospective postmarketing surveillance study in more than
      20,000 patients demonstrated that the overall risk of gastrointestinal or
      operative site bleeding related to parenteral ketorolac therapy was only slightly
      higher than with opioids. However, the risk increased markedly when high dosages
      were used for more than 5 days, especially in the elderly. Acute renal failure
      may occur after treatment with ketorolac but is usually reversible on drug
      discontinuation. In common with other NSAIDs, ketorolac has also been implicated
      in allergic or hypersensitivity reactions. In summary, ketorolac is a strong
      analgesic with a tolerability profile which resembles that of other NSAIDs. When
      used in accordance with current dosage guidelines, this drug provides a useful
      alternative, or adjuvant, to opioids in patients with moderate to severe pain.

PMID- 9010661
TI  - Recent undesirable life events: their influence on subsequent psychopathology.
AB  - Life events appear to exert a range of effects on subsequent behaviour through
      their impact on affective-cognitive processes. Their effects on those
      physiological processes pertinent to psychopathology have yet to be investigated.
      Single events do not exert much risk for subsequent disorder. It is the pattern
      of adverse life experiences, of which recent life events is frequently a
      component, that determines the degree of risk and the mechanisms and processes
      that may lead to subsequent psychopathology. Recall of events that occurred in
      the recent past may be influenced independently by the age of the individual and
      a previous episode of psychiatric disorder. Longitudinal studies determining the
      impact of life events on subsequent behaviour will need to take these features
      into account. There remains no specificity between particular types of recent
      undesirable life events and anxious or depressive disorders. Future longitudinal
      research should employ modern methods of life event data collection and
      measurement. The goal of future longitudinal research should be to determine the
      relative contribution of undesirable and desirable recent life events in the
      presence and absence of other putative casual factors from different domains.
      This should necessarily include social (e.g. long-term difficulties),
      psychological (e.g, temperament (18) or self esteem) and physiological (e.g.
      hypercortisolaemia in adolescent major depression (14, 11) elements. It is only
      through this combination of longitudinal design, together with sensitive and
      concurrent multiple repeat measurements that a greater understanding of the
      mechanisms and processes that determine psychopathology over the course of
      development will occur.

PMID- 9010662
TI  - The children of the Lundby study as adults: a salutogenic perspective.

PMID- 9010663
TI  - Deviant children grown up.

PMID- 9010664
TI  - Vulnerable but invincible: high risk children from birth to adulthood.

PMID- 9010665
TI  - The long-term outcome of childhood empathy disorders.

PMID- 9010666
TI  - The psychopathic personality in a longitudinal perspective.

PMID- 9010667
TI  - The relationship between early school problems and severe psychosocial problems
      up to 18 years of age.

PMID- 9010668
TI  - Psychosocial influence on the physical and mental development of Swedish
      children.

PMID- 9010669
TI  - Children's development related to day-care, type of family and other home
      factors.

PMID- 9010670
TI  - Sex differences in psychomotor and mental development. Results from "Children in
      a new Stockholm suburb--a longitudinal prospective study on children from the
      general population starting at the beginning of pregnancy".

PMID- 9010671
TI  - Cytokine-containing liposomes as vaccine adjuvants.
AB  - The ability of cytokines to regulate and augment an immune response makes them
      likely agents to be included in vaccines. The systemic use of cytokines as
      vaccine adjuvants has been hampered by toxicity at effective doses. More precise
      delivery of cytokines and immunogen can be achieved through the use of
      microparticle carriers such as liposomes. Several cytokines, including IL-2, IL
      7, IL-6 and IFN-gamma have been shown to increase the adjuvant activity of
      liposomes. It may be possible to use certain cytokines to induce immunoglobulin
      production, others to induce cytotoxic T lymphocytes (CTL) and still others to
      promote IgA production at mucosal surfaces. An alternative to liposomes
      containing cytokines may be liposomes containing cytokine-inducing adjuvants such
      as MTPPE, MPL and QS21. This approach may produce undesirable immunomodulators as
      well as beneficial cytokines.

PMID- 9010672
TI  - Role of leukemia inhibitory factor during mammalian development.
AB  - Leukemia inhibitory factor (LIF) is a cytokine that exhibits proliferative,
      survival and differentiation activities on a wide range of cell types. A role for
      LIF in embryonic development is suggested by: i) its ability to stimulate the
      proliferation of embryonic stem (ES) cells in vitro, while maintaining their
      totipotency and ii) by both its maternal and embryonic expression at the time of
      blastocyst implantation. Functional studies of LIF and its receptor during mouse
      embryogenesis have been performed using the techniques of targeted gene
      replacement and transgene expression in ES cells to produce transgenic mice
      bearing either loss- or gain-of-function mutations for LIF activity. Whereas, the
      phenotype observed in the LIF gain-of-function mutant mice supports a role for
      LIF in early embryogenesis, the loss-of-function phenotypes point to more
      specialized functions for LIF in development and further reveal the redundant
      feature of the LIF cytokine/receptor family.

PMID- 9010673
TI  - A decade of accumulated knowledge and emerging answers. The 6th international
      congress on TNF Rhodes, Greece. May 1996.

PMID- 9010674
TI  - Induction by interferons of human eosinophil apoptosis and regulation by
      interleukin-3, granulocyte/macrophage-colony stimulating factor and interleukin
      5.
AB  - The effects of recombinant human interferon alpha (rhIFN-alpha) and interferon
      gamma (rhIFN-gamma) were examined on the apoptosis of human cord blood derived
      eosinophils, obtained after 4 weeks of culture with recombinant human interleukin
      3 (rhIL-3), granulocyte-macrophage-colony stimulating factor (rhGM-CSF) and
      interleukin-5 (rhIL-5). Eosinophil viability decreased remarkably after 1 week
      culture with rhIFN-alpha and rhIFN-gamma. Recombinant rhIFN-alpha also decreased
      the viability of co-existing monocytes/macrophages, whereas in contrast, rhIFN
      gamma increased the percentage of viable monocytes/macrophages. There was no
      synergistic or additional effect of rhIFN-alpha and rhIFN-gamma on eosinophil
      viability. Apoptotic eosinophils, detected by their morphological
      characteristics, or by DNA nick end labeling in situ, increased remarkably after
      incubation with rhIFN-alpha and increased to a lesser extent with rhIFN-gamma.
      The numbers of eosinophil-phagocytosing macrophages increased after culture with
      rhIFN-alpha and also with rhIFN-gamma. In contrast, eosinophilopoietic cytokines
      such as rhIL-3, rhIL-5 and specially rhGM-CSF, significantly increased eosinophil
      viability, and partially rescued the effects of rhIFNs. They also decreased
      apoptotic eosinophil numbers and eosinophil-phagocytosing macrophage numbers.
      These results indicate that eosinophil viability, at least in vitro, can be
      differentially regulated by cytokines produced during the immune response.

PMID- 9010675
TI  - Abnormal organisation of the splenic marginal zone and the correlated
      leukocytosis in lymphotoxin-alpha and tumor necrosis factor alpha double
      deficient mice.
AB  - In this study we further characterized the phenotype at the homeostasis of mice
      genetically deficient in Tumor Necrosis Factor-alpha and Lymphotoxin-alpha (LT
      alpha TNF-alpha -/-). As initially observed in LT-alpha -/- mice, these mice are
      devoid of lymph nodes and Peyer's patches, while in their spleen the white and
      red pulp domains are no more detectable. In the blood the leukocytosis dominated
      by lymphocytosis is not solely due to the absence of lymph nodes. Indeed, this
      abnormality was shown to be correctable by the transfer of wild type bone marrow
      in the absence of lymph node. We now report that the metallophilic macrophages of
      the marginal zone are no more detectable with an antibody reactive to
      sialoadhesin, a macrophage restricted transmembrane molecule known to bind
      myeloid and lymphoid cells. The absence of sialoadhesin within the marginal zone,
      a critical domain for lymphocyte trafficking towards the white pulp suggests a
      possible cellular basis for the observed blood leukocytosis. In addition, in the
      peritoneal cavity of LT-alpha TNF-alpha-/- mice, the size of the resident
      leukocyte population is increased. By their amplitudes these leukocytosis are
      similar within the blood and the peritoneal compartments.

PMID- 9010676
TI  - Interferon-gamma enhances tumor necrosis factor-alpha production by inhibiting
      early phase interleukin-10 transcription.
AB  - The ability of cytokine synthesis inhibitory factor or interleukin-10 (IL-10) and
      interferon-gamma (IFN-gamma) to modulate the production of tumor necrosis factor
      (TNF-alpha) induced by lipopolysaccharide (LPS) was examined in mouse bone marrow
      derived macrophages (BMDM). IFN-gamma profoundly enhances LPS-stimulated TNF
      alpha production, whereas IL-10 is markedly inhibitory, demonstrating the
      opposing effects of IFN-gamma and IL-10 on BMDM. Early neutralization of
      endogenously produced, LPS-stimulated IL-10 markedly enhanced short term TNF
      alpha production, an effect further amplified by the absence of IFN-gamma
      priming. The regulatory effects of IFN-gamma and IL-10 apparently occurred at the
      translational (or post-translational) level, with TNF-alpha mRNA steady-state
      levels remaining unchanged. Furthermore, IFN-gamma exerts its enhancing effect on
      TNF synthesis by the transcriptional inhibition of IL-10. This in vitro finding
      was also confirmed in vivo. In the absence of LPS, IFN-gamma was not capable of
      inducing TNF-alpha production in BMDM, indicating that LPS or other signals are
      necessary for transcriptional activation. Reduced but significant TNF-alpha
      production in LPS-injected IFN-gamma receptor -/- mice suggests that IFN-gamma is
      not an absolute requirement and that other cytokines or cell types contribute in
      a secondary fashion to the priming of LPS-induced TNF-alpha production in vivo.

PMID- 9010677
TI  - Soluble tumour necrosis factor receptor release after anti-CD3 monoclonal
      antibody treatment in mice is independent of tumour necrosis factor-alpha
      release.
AB  - The involvement of TNF-alpha in the release of soluble TNF receptors was assessed
      in mice, treated with anti-CD3 monoclonal antibodies. After treatment with three
      different anti-CD3 mAb, we simultaneously studied serum levels of TNF-alpha,
      soluble TNF receptor P55 and P75. All three anti-CD3 mAb triggered the release of
      both of the soluble TNF receptors, whereas only one of the anti-CD3 mAb triggered
      TNF-alpha release. These data demonstrate that in our model soluble TNF receptor
      release is independent of TNF-alpha release.

PMID- 9010679
TI  - Effects of methyl palmitate on cytokine release, liver injury and survival in
      mice with sepsis.
AB  - The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were
      studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation
      and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was
      shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF)
      and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced
      activation of Kupffer cells resulted in lower levels of inflammatory products
      after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h
      respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h
      after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced
      8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP
      treated mice and survival was significantly prolonged at all intervals, reaching
      45% after six to ten days compared with 3% in control mice. These findings
      suggest that Kupffer cells play an important role in liver damage and survival in
      sepsis.

PMID- 9010678
TI  - Production of prostaglandin E2 and collagenase is inhibited by the recombinant
      soluble tumour necrosis factor receptor p55-human gamma 3 fusion protein at
      concentrations a hundred-fold lower than those decreasing T cell activation.
AB  - TNF-alpha and lymphotoxin alpha (TNF-beta) are pleiotropic cytokines with
      regulatory functions in inflammatory reactions and T cell activation. Natural TNF
      inhibitors such as soluble TNF-binding proteins, i.e. TNFsR55 and TNFsR75, are
      shed from white blood cells and probably other cells. These naturally occurring
      inhibitors of TNF are shown to be 10 times less effective than the bivalent
      antagonist of TNF, recombinant soluble TNF receptor p55-human gamma 3 fusion
      protein (rsTNFR-p55h gamma 3), in controlling the release of prostaglandin E2
      (PGE2) and collagenase by fibroblasts, as well as in controlling T cell
      proliferation. In order to block the action of rhTNF-alpha added to fibroblasts,
      a fivefold excess of rsTNFR-p55h gamma 3 was sufficient, but concentrations of a
      hundred to a thousand times higher were required to obtain a significant
      inhibition of T cell activation. This concentration appears to be required to
      block membrane-bound TNF-alpha on peripheral blood mononuclear cells as shown by
      Scatchard analysis. We additionally show that rsTNFR-p55h gamma 3 at high
      concentrations also blocks T cell activation by dendritic cells. In conclusion
      rsTNFR-p55h gamma 3 has a much higher anti-inflammatory effect than
      immunosuppressive effect.

PMID- 9010680
TI  - Cytokine gene expression in erythroid cells.
AB  - Erythroid nuclear cells have been shown to exert regulatory effects on
      immunopoiesis. We have reported that some of these influences might be mediated
      via soluble factors secreted by nuclear erythroid cells. In this report we
      describe our estimate of the cytokine gene expression in cells isolated from
      individual erythroid colonies by Reverse transcription-Polymerase chain reaction.
      We found in erythroid cells, originated from the bone marrow precursors obtained
      from phenylhydrazine-treated mouse, the expression of the following cytokine
      genes: IL-1 alpha and IL-1 beta, IL-4, IL-6, GM-CSF, gamma-IFN and TGF-beta. In
      contrast, the erythroid cells derived from newborn mouse spleen precursor cells
      expressed IL-1 alpha, IL-1 beta, IL-4, IL-6 and GM-CSF mRNAs but not gamma-IFN
      and TGF-beta mRNAs. No detectable levels of IL-2, IL-3 and IL-5 mRNAs were
      expressed in nuclear erythroid cells. These data provide evidence of the
      expression of mRNAs coding in the set of immunoregulatory cytokines in immature
      erythroid progenitor cells in mouse.

PMID- 9010681
TI  - Interleukin-1 induced signalling: biphasic activation of mitogen-activated
      protein kinase kinase and mitogen-activated protein kinases in HeLa cells.
      Involvement of phosphoprotein phosphatases.
AB  - Results of this study document a biphasic activation of protein kinases of the
      MAP kinase cascade-MEK and MAP kinases-upon interleukin-1 stimulation in human
      HeLa cells. The specific activities of both MEK and MAP kinases were increased
      within 1 min, declined rapidly to control levels and increased again after 15 min
      of interleukin-1 stimulation. Inhibition by okadaic acid of serine/threonine
      specific phosphatases resulted in a marked increase in interleukin-1 stimulated
      MEK and MAP kinase activities. Elevation by interleukin-1 of the specific
      activities of MEK and MAP kinases correlated with suppression of serine/threonine
      phosphatases in the late phase of stimulation. The data indicate, that enhanced
      phosphorylation of cellular proteins by enzymes of the MAP kinase cascade might
      represent a fine balance between activated protein kinases and repressed
      phosphoprotein phosphatase 2A in interleukin-1 stimulated HeLa cells.

PMID- 9010682
TI  - Serum interleukin-10 in acquired immunodeficiency syndrome lymphoma patients.
      Seroco-Hemoco Study Group.
AB  - Interleukin-10 (IL-10) has multiple effects on lymphoid development, particularly
      as a stimulant of activated B-cell proliferation and differentiation. It is
      thought that IL-10 might play a role in the development of B lymphoid
      malignancies based on the observation that lymphomatous tissues from HIV+
      patients contain numerous cells containing IL-10 mRNA as well as IL-10 protein.
      The aim of this study using an Elisa test was to analyze IL-10 in the serum of 18
      HIV+ patients with non Hodgkin's B lymphoma (NHL) and compared the presence of
      this cytokine in the serum of 18 HIV+ patients without NHL. In this comparative
      study we also considered the different parameters such as the mode of
      contamination, sex, age and number of CD4 cells. 44% of the patients with HIV
      related NHL had significant levels of IL-10 (> or = 12 pg/ml) in their serum, in
      comparison to the patients without NHL who did not show detectable serum IL-10.

PMID- 9010683
TI  - Suppressive effect of hepatitis B virus on the induction of interleukin-1 beta
      and interleukin-6 gene expression in the THP-1 human monocytic cell line.
AB  - The major target organ for Hepatitis B Virus (HBV) is the liver, but extrahepatic
      sites including monocytes express receptors for HBV and may become infected.
      Therefore, we investigated the effect of HBV on the in vitro expression of
      interleukin-beta (IL-1 beta) and interleukin-6 (IL-6) by the monocytoid cell line
      THP-1, exposed to various stimuli (LPS, PMA or both). Nonstimulated THP-1 cells
      did not synthesize IL-1 beta and IL-6, even after in vitro exposure to HBV. LPS
      stimulation alone induced moderate secretion of both IL-1 beta and IL-6 (300
      pg/ml). After induction of macrophage differentiation by PMA, THP-1 cells
      acquired adherence and expressed a higher level of IL-1 beta (up to 2 ng/ml) but
      did not synthesize IL-6. Treatment of THP-1 cells with PMA and LPS caused the
      highest production of both IL-1 beta and IL-6 (> 5ng/ml). In vitro exposure of
      PMA + LPS-stimulated THP-1 cells to HBV resulted in secretion of both HBsAg and
      preS2Ag which was maintained over 10 days of culture. Southern blot technique was
      used to study the state of HBV DNA in the cells. Hybridization of non-digested
      cellular DNA showed only high molecular weight HBV DNA forms. The HindIII
      restriction pattern revealed bands corresponding to large DNA fragments and the
      presence of bands at the 3.2 kb position. Under these conditions (PMA + LPS), HBV
      inhibited the production of IL-1 beta and IL-6 proteins and completely suppressed
      the IL-1 beta and IL-6 mRNA. Thus, our findings (i) strongly support a
      relationship between the state of cell differentiation and susceptibility of
      cells to HBV infection, and (ii) demonstrate that HBV exerts an inhibitory effect
      on the induction of IL-1 beta and IL-6 genes expression in monocytic THP-1 cells.
      These results suggest that HBV leads to a fall of pro-inflammatory cytokine
      production by monocytes/macrophages, which may contribute to impaired host immune
      response during infection.

PMID- 9010684
TI  - IV International Conference on Cytokines. Ares-Serono Foundation (under the
      auspices of the European Cytokine Society). Florence, Italy. March 20-22, 1996.
      Report and abstracts.

PMID- 9010685
TI  - The differentiation of propafenone from other class Ic agents, focusing on the
      effect on ventricular response rate attributable to its beta-blocking action.
AB  - Propafenone, encainide and flecainide have been categorized as class Ic
      antiarrhythmic drugs, since they produce similar clinical electrophysiological
      effects. However, propafenone has also modes of action that differ substantially
      from pure class Ic activity. The most distinctive electrophysiological difference
      from other class Ic antiarrhythmic drugs stems from its structural similarity
      with other beta-adrenoceptor antagonists. The potency of the beta-adrenoceptor
      blocking property of propafenone has been estimated to range from 1/20 to 1/50
      that of propranolol on a molar basis. Because the plasma concentrations of
      propafenone during long-term treatment may be up to 50 or more times that of
      propranolol, the beta-adrenoceptor blocking effect may be clinically relevant.
      However, although the beta-adrenoceptor blocking effects are readily demonstrable
      in vitro, clinical data are more inconsistent, because the beta-adrenoceptor
      blocking action has been reported as being undetectable to significant. During
      atrial fibrillation, with or without accessory pathways, propafenone exerts
      effective and prompt control of the ventricular rate in patients who fail to
      convert to sinus rhythm. However, compared with other class Ic antiarrhythmic
      drugs, propafenone has not been proved generally better in controlling the
      ventricular rate.

PMID- 9010686
TI  - Evaluation of personality as a component of the healthy condition of volunteers
      participating in phase I studies.
AB  - OBJECTIVE: The present study was conceived in order to recommend use of the
      Minnesota Multiphasic Personality Inventory for the evaluation of the personality
      of volunteers participating in Phase I clinical trials. The study was intended to
      describe personality profiles as objectively as possible, attempting to identify
      any common traits or tendencies, and to evaluate whether age or cultural
      background can be associated with significant differences in volunteer
      personality profiles. SUBJECTS: 358 subjects were evaluated (290 males and 68
      females; mean age 30 y, range 18-78 y). Mean values of scales and indices were
      compared and analysed, both for the sample as a whole and on the basis of its
      breakdown according to sex, age and education. RESULTS: No psychopathological
      values were found in terms of sex and education. The mean profile showed common
      traits of a substantially balanced, self-assured, reliable person, motivated by
      extremely realistic objectives. CONCLUSION: The Minnesota Multiphasic Personality
      Inventory seems to be a useful tool for screening healthy volunteers.

PMID- 9010687
TI  - Subjective symptoms and quality of life in healthy subjects during a phase I
      study.
AB  - OBJECTIVE: Participants in a phase I study were interviewed in order to establish
      the incidence and variability of subjective symptoms and changes in quality of
      life during phase I trials. METHODS: The healthy subjects were randomized to
      receive a single dose of either 0.5 mg digoxin or an equivalent amount of each of
      four digitaloid mixtures every 14 days. The trial involved five 24-h monitoring
      periods. The duration of the study was 57 days. Wellbeing, subjective symptoms
      and quality of life were measured before, during and after the trial using the
      Freiburg Symptoms List (FSL), Wellbeing Scales (WBS), and Life Satisfaction
      Questionnaire (LSQ). RESULTS: Eight healthy subjects (25 years) were enrolled in
      the study. Their subjective symptoms were below the reference values for healthy
      subjects for each test but above the theoretical minimum and maximum values for
      total wellbeing, indicating that healthy subjects-not just patients-display
      subjective symptoms and impairment of wellbeing to a greater or lesser extent
      prior to a clinical trial. In terms of the total study population, comparison of
      the questionnaire scores before, during and after the study disclosed no
      significant changes in wellbeing or quality of life. However, some participants
      displayed marked intraindividual fluctuation. CONCLUSIONS: A careful exploration
      of the baseline symptoms is necessary even in healthy subjects to avoid
      observation bias. The symptom course differs greatly from individual to
      individual; therefore in a phase I study only group scores of wellbeing should be
      used to assess the possible effects of trial-related factors. A setting like the
      one used in our study does not impair the quality of life of healthy subjects and
      as such can be regarded as a fairly neutral means of measuring wellbeing.

PMID- 9010689
TI  - Mechanisms of tolerance during treatment with nitroglycerin patches for 24 h.
AB  - OBJECTIVE: We examined the relationship between tolerance development,
      counterregulatory responses and arterial vasodilating effects evaluated by
      digital pulse plethysmography. METHODS: Twenty patients with stable angina
      pectoris were exercise tested before, after 2 and after 24 h of open nitrate
      patch treatment. RESULTS: The effects observed after 2 h of treatment on exercise
      duration, ST-segment depression, blood pressure and heart rate were lost in most
      individuals after 24 h. In contrast, the effects on the arterial pulse curves
      persisted after 24 h, with a mean change from baseline of 29%, compared to 33% at
      2 h. After 24 h, a significant decrease in haematocrit and an increase in body
      weight were observed. The haematocrit changes correlated with the loss of
      clinical efficacy (r = 0.57 for ST-segment depression, and r = 0.54 for exercise
      duration). CONCLUSION: Clinical nitrate tolerance may be observed despite
      maintenance of the arterial vasodilating effects, and tolerance is more related
      to plasma volume expansion as a counterregulatory mechanism.

PMID- 9010688
TI  - Tolerance evaluation of L-asparaginase loaded in red blood cells.
AB  - OBJECTIVE: A pilot clinical study was conducted to evaluate the toxicity of a
      single dose of L-asparaginase loaded in red blood cells (RBCs). METHODS: Thirteen
      patients received a single dose of L-asparaginase in the range 30-200 i.u.kg-1.
      The enzyme was loaded in one autologous blood unit using a lysis-resealing
      process. A control population of 33 patients receiving L-asparaginase
      intravenously were tested in parallel. IgG, IgM and IgE class anti-L-asparaginase
      antibodies were detected using specific radioimmunoassays. RESULTS: L
      Asparaginase pharmacodynamic parameters may be greatly improved by administration
      of the drug after internalisation in RBCs as compared to intravenous injection of
      free drug. The drug elimination was prolonged and similar to that of circulating
      carrier. After one injection of 30 i.u.kg-1, plasma L-asparagine was eliminated
      in 10 days and this was extended to 50 days for 150-200 i.u.kg-1. The drug was
      well tolerated and only transient variations were observed for some of the
      biological parameters measured. We did not reach the maximum tolerable dose (MTD)
      of L-asparaginase loaded in RBCs. No significant clinical toxicity was detected.
      In particular, no immune adverse effects were observed. CONCLUSION: This study
      opens new perspectives for the clinical utilisation of L-asparaginase. This mode
      of administration of the drug is able to improve pharmacodynamic parameters and
      enzymic efficacy and to increase the general tolerance of the treatment.

PMID- 9010690
TI  - Effects of ketoprofen and ibuprofen on platelet aggregation and prostanoid
      formation in man.
AB  - OBJECTIVE: In the present randomized, fourway crossover study we determined the
      effects of two oral doses each of ketoprofen and ibuprofen on platelet
      aggregation and prostanoid formation in man. METHODS: Twelve healthy female
      volunteers received for 2 consecutive days, followed by a 5-day drug-free
      interval, one of the following: ketoprofen 3 x 25 mg per day, or ketoprofen 3 x
      50 mg per day, or ibuprofen 3 x 200 mg per day, or ibuprofen 3 x 400 mg per day.
      The response criteria, determined before and on the 2nd day of each treatment
      period, were: maximal platelet aggregation in response to 1.0 mmol.l-1
      arachidonic acid measured by the method of Born and Cross, thromboxane B2 (TXB2)
      concentration in platelet-rich plasma after aggregation measured by
      radioimmunoassay, and PGE-M, the index metabolite of total body prostaglandin E2
      (PGE2) production, assessed by gas chromatography/tandem mass spectrometry using
      18O2-PGE-M as internal standard. RESULTS: Platelet aggregation was significantly
      reduced by ketoprofen 3 x 25 mg per day (-57%) and ketoprofen 3 x 50 mg per day (
      85%) as compared to control, whereas ibuprofen 3 x 200 mg per day (-3%) and
      ibuprofen 3 x 400 mg per day (-22%) had no significant effects. TXB2 synthesis
      was significantly decreased by ketoprofen 3 x 25 mg per day (-72%), ketoprofen 3
      x 50 mg per day (-97%) and ibuprofen 3 x 400 mg per day (-48%) as compared to
      control; ibuprofen 3 x 200 mg per day did not reduce TXB2 formation significantly
      (-23%). All four treatments reduced 24-h urinary excretion of PGE-M significantly
      in the range of -39% (ketoprofen 3 x 25 mg per day) to -53% (ibuprofen 3 x 400 mg
      per day) without significant differences between treatments. CONCLUSION: Our data
      show that both ketoprofen dosages were more effective in inhibition of platelet
      aggregation and platelet thromboxane synthesis than ibuprofen in low or high
      dosage. Total body synthesis of the E-prostaglandins was inhibited by all drug
      schedules without significant differences between treatments.

PMID- 9010691
TI  - Progress in the prostaglandin E1-therapy of the intermittent claudication by
      means of bolus injections of LIPO-prostaglandin E1 (LIPO-PGE1).
AB  - OBJECTIVE: We compared the efficacy of a bolus injection (5 min) of LIPO-PGE1
      (Prostaglandin E1 in lipid emulsion) with conventional PGE1-cyclodextrin (PGE1
      cyclodextrin) infusions (2 h) in patients with intermittent claudication. The
      quantitative blood-flow in the common femoral artery was measured using a
      computerized ultrasound Doppler system (MAVIS). We also monitored the
      transcutaneous oxygen pressure, the skin temperature on the foot, and the
      reactive change in blood pressure and pulse as well as side effects. RESULTS:
      Dose finding of LIPO-PGE1: After bolus injection of 30, 50, and 80 micrograms
      LIPO-PGE1 a significant dose-dependent increase of the blood flow in the leg
      (+96.9%, 80 micrograms) with a peak 3 h after injection was seen. After LIPO-PGE1
      we observed an enhanced microcirculation (significant rise in the transcutaneous
      oxygen pressure and the skin temperature on the foot). We noted longer lasting
      pharmacodynamic properties with LIPO-PGE1 (50 micrograms) compared to PGE1
      cyclodextrin (60 micrograms). Comparison to PGE1-cyclodextrin: In a cross-over,
      placebo-controlled study, 20 patients with intermittent claudication received 4
      weeks therapy with a bolus of 50 micrograms LIPO-PGE1 or a 2 h infusion of 60
      micrograms PGE1-cyclodextrin per day. A significant increase in the blood flow
      was measured at the end of 4 weeks therapy compared to the initial values before
      treatment. This rise correlates significantly with the increase in the patient's
      maximal walking distance (+112%, LIPO-PGE1). Compared to conventional PGE1
      cyclodextrin infusions given over 2 h, a clearly prolonged increase in perfusion
      of the affected limb after LIPO-PGE1 was demonstrated. No serious adverse effects
      were observed.

PMID- 9010692
TI  - Colchicine enhances intestinal permeability in patients with familial
      Mediterranean fever.
AB  - OBJECTIVE: Colchicine therapy is complicated by frequent gastrointestinal adverse
      effects. METHODS: We compared intestinal permeability in 21 patients with
      familial Mediterranean fever on long-standing colchicine therapy (mean 5.8 years)
      and significant gastrointestinal complaints and 12 untreated patients and 14
      healthy volunteers. The double probe (lactulose/mannitol) permeability test was
      performed using a hyperosmolar test solution (1580 mosmol) and the differential
      urinary recovery ratios were calculated. RESULTS: Familial Mediterranean fever
      patients on colchicine therapy had significantly higher lactulose/mannitol
      urinary excretion ratios (0.073) compared to untreated patients (0.035) and to
      healthy controls (0.021). Untreated familial Mediterranean fever patients had
      significantly greater urinary lactulose/mannitol recovery ratios than controls (P
      < 0.02). No correlation was found between the degree of enhanced permeability and
      the length of exposure to the drug or the severity of clinical symptoms.
      CONCLUSIONS: Intestinal permeability was significantly enhanced in patients with
      familial Mediterranean fever treated with colchicine.

PMID- 9010693
TI  - Release of cytokines by a fermented lectin-1 (ML-1) free mistletoe extract
      reflects differences in the reactivity of PBMC in healthy and allergic
      individuals and tumour patients.
AB  - OBJECTIVE: Mistletoe extracts are used in adjuvant cancer treatment, but little
      is known concerning their mode of action. There is, however, evidence that
      antigens in these extracts may stimulate cells of the immune system, thereby
      modifying the altered immunological reactivity in tumour patients. METHODS: In
      order to find out whether the postulated immunomodulatory properties of mistletoe
      extracts are mediated by cytokines, a spectrum of different cytokines was
      analysed in the supernatants of peripheral blood mononuclear cells (PBMC) from
      healthy (n = 23) and allergic (n = 16) individuals after stimulation with the
      fermented mistletoe lectin-1 (ML-1) free mistletoe extract Iscador Pini (IP) in
      vitro, and their cytokine patterns were compared to those from tumour patients
      with either breast cancer (n = 20) or colorectal tumours (n = 22). RESULTS: PBMC
      from healthy and allergic individuals produced high levels of TNF-alpha and IL-6
      and to a lesser extent Th1- and Th2-related cytokines. This finding was in
      contrast to data obtained in tumour patients. Thus, the concentration of TNF
      alpha was significantly lower in the cell cultures from breast cancer patients
      than in controls, and patients with colorectal tumours released IFN-gamma/IL-2
      (5%) in the supernatants significantly less frequently than PBMC from healthy
      controls (26%). Similar results were obtained when the Th1- and
      monocyte/macrophage-related cytokines were analysed in the unstimulated cell
      cultures. CONCLUSIONS: These in vitro studies provide evidence that there is a
      reduced immunological reactivity to the fermented ML-1 free mistletoe extract in
      tumour patients and may give some clues as to how mistletoe-derived antigens
      could act on immune cells involved in the tumour defence.

PMID- 9010694
TI  - Squamometry in rating the efficacy of topical corticosteroids in atopic
      dermatitis.
AB  - OBJECTIVE: Squamometry is a non-invasive test allowing a reproducible rating of
      cutaneous xerosis including atopic dermatitis lesions. The method was used to
      compare the efficacy of proprietary topical corticosteroids in alleviating signs
      of atopic xerosis. RESULTS: The steroid compounds and their vehicles improve the
      texture of the stratum corneum at different rates after treatment for 1 week.
      Some differences in efficacy may be explained by the nature of the vehicle, which
      enhances the basic pharmacological activity of the corticosteroid itself.

PMID- 9010696
TI  - Calcium antagonist treatment and cardiovascular responses to a cold pressor test
      at high altitude.
AB  - OBJECTIVE: We assessed the effects of the calcium antagonist felodipine on blood
      pressure, heart rate, oxygen saturation and cardiovascular responses to a cold
      pressor test at an altitude of 5200 m. Sixteen healthy climbers participated. A
      double-blind, placebo-controlled, randomized, crossover design was used. Placebo
      or felodipine were taken for 2 days and the treatment was changed after 3 days
      washout. RESULTS: During felodipine treatment there were no significant changes
      in blood pressure (125/89 vs 127/86 mmHg), heart rate (82 vs 81 beats.min-1) or
      oxygen saturation (86% vs 86%). Moreover, there were no changes in the
      cardiovascular responses to the cold pressor test. CONCLUSION: Felodipine is well
      tolerated at high altitude. It does not induce hypotension in normotensive men
      and does not affect cardiovascular reactivity to cold stress.

PMID- 9010695
TI  - Haemodynamic effects and pharmacokinetics of oral d- and l-nebivolol in
      hypertensive patients.
AB  - OBJECTIVE: Nebivolol is a selective beta 1-adrenergic receptor blocker possessing
      an ancillary vasodilating effect. The objective of the present study was to study
      the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a
      double-blind, placebo-controlled cross-over study. METHODS: Fifteen patients, 12
      men and 3 women, with essential hypertension were investigated. Blood pressure
      and peripheral circulation were determined after acute oral nebivolol
      administration, 5 mg daily, and after 4 weeks treatment. RESULTS: The acute
      effect on blood pressure upon single-dosing was weak and non-significant. After 4
      weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure
      (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared
      to placebo. Following the first dose the venous volume was higher on placebo
      (5.88 ml.100 ml-1 tissue) as compared to active nebivolol treatment (5.17 ml.100
      ml-1 tissue), while there were no statistically significant differences with
      regard to venous plethysmographic findings after 1 month on placebo (5.53 ml.100
      ml-1 tissue) or on active treatment (5.97 ml.100 ml-1 tissue). Calculated
      peripheral resistance did not differ between active treatment (617 units) or
      placebo (548 units) after the first dose, whereas it was significantly lowered
      after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593
      units). CONCLUSIONS: Oral nebivolol 5 mg once daily lowered blood pressure and
      heart rate during steady state compared to placebo. Moreover, venous volume was
      reduced during acute but not steady-state dosing, while peripheral resistance was
      unaffected in the acute phase but reduced during steady state. Plasma
      concentrations of the separate enantiomers plus hydroxylated metabolites after
      the first and last dose in hypertensive patients were similar to those in healthy
      subjects.

PMID- 9010697
TI  - Neutral endopeptidase 24.11 inhibition may not exhibit beneficial haemodynamic
      effects in patients with congestive heart failure.
AB  - OBJECTIVES: Inhibition of neutral endopeptidase 24.11 (NEP) prevents degradation
      of plasma atrial natriuretic peptide (ANP), a substance with vasodilatory and
      natriuretic properties. The aim of the study was to investigate the haemodynamic
      and endocrine effects of the NEP inhibitor candoxatril in patients with
      congestive heart failure (CHF). METHODS: In a randomized double-blind, parallel
      group study design, 24 patients with CHF received a 10-day oral drug treatment
      with candoxatril (25, 100 or 400 mg b.i.d.) or placebo. Invasive haemodynamics
      and laboratory parameters were measured on days 1 and 10. RESULTS: On the first
      treatment day, candoxatril produced a dose-dependent increase in plasma cyclic
      GMP, the second messenger of ANP. At doses of 100 and 400 mg, candoxatril induced
      an increase (!) in systemic vascular resistance (SVR) and a decrease in cardiac
      index (CI), which was not observed with placebo and the lower candoxatril dose.
      CONCLUSION: Despite significant activation of the ANP system, reflected by a dose
      dependent increase in plasma cyclic GMP concentrations, high doses of candoxatril
      induced systemic vasoconstrictory rather than vasocilatory effects in patients
      with CHF. Therefore NEP inhibition by candoxatril may not exhibit beneficial
      haemodynamic effects in CHF.

PMID- 9010698
TI  - Simultaneous inhibition of catecholamine-O-methylation by entacapone and neuronal
      uptake by imipramine: lack of interactions.
AB  - OBJECTIVE: We have evaluated the effects of simultaneous inhibition of catechol-O
      methyltransferase (COMT) by entacapone and of neuronal monoamine reuptake by
      imipramine on haemodynamics and catecholamine metabolism, and the safety and
      tolerability of the drug combination in healthy women. METHODS: In a randomized,
      single-dose, single-blind, cross-over study, 12 healthy women were given placebo,
      entacapone (200 mg), imipramine (75 mg) or entacapone and imipramine in
      combination. Heart rate, blood pressure, systolic time intervals, and plasma
      concentrations of catecholamines and their metabolites were measured at rest and
      during exercise. RESULTS: The only drug-related effect on haemodynamics was an
      increase in heart rate during exercise after imipramine. The increase in heart
      rate after the combination of entacapone and imipramine was similar to that after
      imipramine alone. Entacapone alone had no effects on haemodynamics. Imipramine
      and entacapone had no significant effects on the plasma concentrations of
      noradrenaline and adrenaline. No interactions between entacapone and imipramine
      were detected.

PMID- 9010699
TI  - Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and
      phenprocoumon in man.
AB  - OBJECTIVE: Pantoprazole is a selective proton pump inhibitor characterized by a
      low potential to interact with the cytochrome P450 enzymes in man. Due to the
      clinical importance of an interaction with anticoagulants, this study was carried
      out to investigate the possible influence of pantoprazole on the pharmacodynamics
      and pharmacokinetics of phenprocoumon. METHODS: Sixteen healthy male subjects
      were given individually adjusted doses of phenprocoumon to reduce prothrombin
      time ratio (Quick method) to about 30-40% of normal within the first 5-9 days and
      to maintain this level. The individual maintenance doses remained unaltered from
      day 9 on and were administered until day 15. Additionally, on study days 11-15,
      pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the
      prothrombin time ratio was determined on days 9 and 10 (reference value) and on
      days 14 and 15 (test value), and the ratio test/reference was evaluated according
      to equivalence criteria. RESULTS: The equivalence ratio (test/reference) for
      prothrombin time ratio was 1.02 (90% confidence interval 0.95-1.09), thus
      fulfilling predetermined bioequivalence criteria (0.70-1.43). The pharmacokinetic
      characteristics AUC0-24h and Cmax of S(-)- and R(+)-phenprocoumon were also
      investigated using equivalence criteria. Equivalence ratios and confidence limits
      of AUC0-24h and of Cmax of S(-)-phenprocoumon (0.93, 0.87-1.00 for AUC0-24h;
      0.95, 0.88-1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82-0.96; 0.9, 0.83
      0.98) were within the accepted range of 0.8-1.25. CONCLUSION: Pantoprazole does
      not interact with the anticoagulant phenprocoumon on a pharmacodynamic or
      pharmacokinetic level. Concomitant treatment was well tolerated.

PMID- 9010700
TI  - How many patients and blood levels are necessary for population pharmacokinetic
      analysis? A study of a one compartment model applied to cyclosporine.
AB  - OBJECTIVE: This paper describes a method to determine the number of patients and
      the number of blood levels which are appropriate for a pharmacokinetic population
      analysis. METHODS: We studied this question by performing 203 runs of population
      analysis, using the NPEM algorithm with a one compartment model, starting with
      only one patient and only one blood level, then 2 patients with one blood level
      each, until reaching 38 patients each with 5 blood levels. Data were obtained
      from liver transplant patients treated with cyclosporine. RESULTS: For 2, 3, 4 or
      5 blood levels, the values of median clearance (CL) converged and became almost
      equal after about 10 patients were studied. The value then remained stable and
      the variation was fairly small. With only one blood level per patient, the
      variation was greater. In contrast, with one blood level, median CL became
      similar to groups having 2, 3, and 4 blood levels only after about 35 patients
      had been studied, versus about 10. Similar results were found for the median
      values of the volume of distribution (V). For a one compartment model with
      parameters of V and CL, from 15 to 20 patients with 2 blood levels may be enough
      to perform a reasonable population pharmacokinetic analysis; the values of the
      pharmacokinetic parameters were very similar to those obtained with 3 to 5 blood
      levels and with more patients. However, a subpopulation probably requires more
      patients and at least 4 or 5 blood levels per patient to be recognised.
      CONCLUSION: Examination of converging pharmacokinetic parameter values by
      stepwise increases in the number of patients and blood levels appears to be a
      pragmatic and empirical approach to determine the possible number of patients and
      blood levels required for population pharmacokinetic analysis.

PMID- 9010701
TI  - Codeine and morphine in extensive and poor metabolizers of sparteine:
      pharmacokinetics, analgesic effect and side effects.
AB  - OBJECTIVE: Codeine O-demethylation to morphine is catalysed by the genetic
      polymorphic sparteine oxygenase (CYP2D6). The objective of the present study was
      to assess the analgesic effect of codeine on different types of experimental pain
      in relation to sparteine phenotype. METHODS: Fourteen extensive (EMs) and 14 poor
      metabolizers (PMs) of sparteine completed a randomized, double-blind, three-way,
      cross-over study with a single oral dose of codeine (75 or 100 mg) against
      morphine (20 or 30 mg) and placebo. Pain tests performed before and 1, 2, 3, and
      4 h after medication included the cold pressor test and pain thresholds for heat
      and pressure stimulation. Adverse effects were rated by a structured interview.
      RESULTS: After morphine, morphine and morphine-6-glucuronide were present in
      equal amounts in plasma of PMs and EMs. After codeine, neither morphine nor
      morphine-6-glucuronide could be detected in 13 of the 14 PMs, whereas at least
      one of the compounds could be detected in all EMs. Peak pain and discomfort rated
      on a VAS scale during the cold pressor test were significantly reduced by
      morphine in both EMs and PMs, with a median peak change of 8.5 and 7.0 mm,
      respectively, for peak pain, and 11.5 and 15.5 mm, respectively, for discomfort.
      Codeine only reduced these pain measures significantly in EMs, with a median peak
      change of 5.5 mm for peak pain and 10.5 mm for discomfort. Pain detection and
      tolerance thresholds to heat and pressure were not consistently altered by either
      morphine or codeine. In PMs, adverse effects were significantly more pronounced
      on morphine than on codeine and only showed a slight difference between codeine
      and placebo. In EMs, there was no difference between codeine and morphine and
      more pronounced adverse effects on both drugs as compared to placebo. CONCLUSION:
      This study confirms that codeine O-demethylation depends on CYP2D6; it shows that
      the 6-glucuronidation of morphine is independent of CYP2D6; it supports the
      theory that the analgesic effect of codeine depends on its O-demethylation; and
      it indicates that this is probably also the case for the adverse effects. The
      results lend no support to the suggestion of a non-opioid analgesic effect of
      codeine.

PMID- 9010702
TI  - Characterization of the cytochrome P450 involved in side-chain oxidation of
      cyclophosphamide in humans.
AB  - OBJECTIVE: Cyclophosphamide (CP) is an antineoplastic prodrug which requires
      bioactivation (4-hydroxylation) by the cytochrome P450 (CYP) enzymes in human
      liver. In parallel, P450-mediated side-chain oxidation (N-dealkylation) leads to
      the formation of the non-alkylating dechloroethylcyclophosphamide (DCI-CP) and
      chloroacetaldehyde, the latter being a potential neurotoxic agent. The enzyme
      responsible for side-chain oxidation has not been identified yet. We therefore
      used an in vitro approach to characterize the enzyme involved in N-dealkylation
      of CP. METHODS: CP was incubated with the microsomal fraction of human liver in
      the presence of specific inhibitors for some P450 enzymes and in the presence of
      stable expressed P450 enzymes. Dechloroethylcyclophosphamide was analysed using
      gas chromatography and nitrogen-phosphorus detection. RESULTS: Formation of DCl
      CP increased linearly with substrate concentration over the entire concentration
      range (20 mumol.l-1 to 36 mmol.l-1). Saturation of the enzyme was not observed.
      Incubation with stable expressed P450 enzymes and inhibition experiments
      indicated that CYP3A4 was the major enzyme involved in side-chain oxidation of
      CP. CONCLUSION: Our in vitro data indicate that side-chain oxidation of CP occurs
      in dose-dependent fashion in men with no saturation of this pathway even
      following dose escalation. Thus enhanced neurotoxicity following CP
      administration may result in the setting of high-dose chemotherapy. Moreover, we
      conclude that CP has the potential to interact with other CYP 3A4 substrates.

PMID- 9010703
TI  - The single and multiple dose pharmacokinetics of pranlukast in healthy
      volunteers.
AB  - OBJECTIVE: The pharmacokinetics of pranlukast, a leukotriene LTD4 antagonist,
      were studied in 48 young, healthy subjects after single and repeated oral doses
      (given every 12 h) ranging from 112.5 to 675 mg. The doses were administered 30
      minutes after a light breakfast. RESULTS: Maximal drug concentrations generally
      occurred between 2 and 6 h after dosing, and there was some evidence of an
      absorption lag-time. Secondary peaks were observed in the plasma concentration
      vs. time profiles of many of the study subjects after both single and repeated
      doses, particularly during the period of maximum drug absorption. In general,
      after both single and repeated doses, there were related increases in the
      corresponding Cmax and AUC with a rise in dose, although the increase was
      diminished at doses above 450 mg. With repeated dosing of pranlukast the mean AUC
      was generally higher (up to 1.6-fold), and the higher plasma concentrations
      allowed characterisation of a longer mean t 1/2 than after single dose
      administration. The mean steady-state trough plasma concentrations attained after
      evening doses were considerably higher (up to 14-fold) than those obtained after
      the morning dose. CONCLUSION: The data suggested that the pharmacokinetics of
      pranlukast are influenced by the time of dosing. Based on analysis of urinary 6
      beta-hydroxycortisol excretion, there was no evidence that pranlukast modified
      the metabolic activity of cytochrome P-450 3A isoenzymes.

PMID- 9010704
TI  - Pharmacokinetics of meloxicam in patients with end-stage renal failure on
      haemodialysis: a comparison with healthy volunteers.
AB  - OBJECTIVE: The pharmacokinetics of meloxicam have been studied following
      administration of a single 15-mg capsule to 12 patients with end-stage renal
      failure. Pharmacokinetic parameters were determined after haemodialysis. The
      pharmacokinetic profile obtained in these patients is compared to data obtained
      from age- and gender-matched healthy volunteers. RESULTS: Total plasma meloxicam
      concentrations were lower in patients with end-stage renal failure (AUC0-infinity
      12.6 micrograms.h.ml-1) in comparison with healthy volunteers (AUC0-infinity 39.3
      micrograms.h.ml-1). This was reflected by an increase in total clearance (+211%).
      However, there was an enhanced free meloxicam fraction (unbound drug) in the end
      stage renal failure patients (0.9% vs. 0.3% in healthy volunteers). This was
      observed in association with raised free Cmax (5.0 vs. 2.6 ng/ml) but similar
      free AUC0-infinity (0.13 vs. 0.11 microgram.h.ml-1) in both groups. Therefore,
      the raised free fraction is compensated for by the increased total clearance such
      that no accumulation of meloxicam occurs. Meloxicam plasma concentrations were
      similar before and after haemodialysis. CONCLUSION: Meloxicam has displayed a
      pharmacokinetic profile in end-stage renal failure which is similar to that
      observed for other highly protein bound nonsteroidal anti-inflammatory drugs
      (NSAIDs). However, in view of the higher free Cmax value, and despite no evidence
      of accumulation, it may be prudent to treat this group of patients with a 7.5-mg
      dose of meloxicam. This is the lower dose normally recommended for adults.
      Meloxicam is not dialysable.

PMID- 9010705
TI  - Transdermally administered nicotine accumulates in gastric juice.
AB  - METHODS: Transdermal nicotine patches (Nicorette 15 mg.16 h-1) were administered
      to 7 healthy volunteers. Nicotine concentrations in gastric juice were monitored
      for 8 h via a naso-gastric tube and so was nicotine in saliva and plasma.
      RESULTS: Nicotine accumulated in gastric juice, the average concentration being
      60.6-times higher than in plasma. In saliva, too, the concentration was higher
      than in plasma, the average ratio being 10.5. These results strongly suggested
      ion-trapping of nicotine base in the acidic gastric juice and possibly also in
      the acinar cells, followed by active secretion. It is hypothesised that
      accumulation in saliva occurs via a similar mechanism. Pretreatment with
      omeprazole did not increase the pH to a sufficiently high degree to test the
      hypothesis that the accumulation of nicotine in gastric juice was pH dependent.
      CONCLUSION: Transdermal administration of nicotine produced a high intragastric
      concentration. The clinical consequence of this effect of long-term nicotine
      replacement therapy during smoking cessation is unclear.

PMID- 9010706
TI  - Absorption rate of methylxanthines following capsules, cola and chocolate.
AB  - OBJECTIVE: To compare caffeine and theobromine absorption after oral
      administration of capsules, cola beverage and chocolate candy. METHODS: Three
      males and four females who abstained from methylxanthines received five
      methylxanthine-containing treatments: caffeine in capsules (72 mg), administered
      twice; theobromine in capsules (370 mg); cola beverage (72 mg caffeine) and
      chocolate candy (72 mg caffeine and 370 mg theobromine). Plasma methylxanthine
      levels were assayed from samples collected before and 0.25, 0.50, 0.75, 1.0, 1.5,
      2.0, and 3.0 h after caffeine capsule and cola treatments and, additionally, at
      4.0 and 6.0 h after theobromine capsule and chocolate treatments. RESULTS:
      Caffeine plasma concentrations increased rapidly and peaked at approximately 30
      min following both capsule treatments 1 (Cmax: 1.93 micrograms.ml-1); and 2
      (Cmax: 2.05 micrograms.ml-1). Relative to capsules, caffeine absorption from cola
      and chocolate was delayed and produced lower maximum caffeine plasma
      concentrations which peaked 1.5-2.0 h after treatment (For cola, Cmax: 1.57
      micrograms.ml-1); and for chocolate, Cmax: 1.50 micrograms.ml-1. Theobromine
      plasma concentrations peaked approximately 3 h after capsule administration
      (Cmax: 6.72 micrograms.ml-1). Relative to capsules, theobromine absorption from
      chocolate was more rapid and produced higher maximum theobromine plasma
      concentrations which peaked approximately 2 h after treatment (Cmax: 8.05
      micrograms.ml-1). CONCLUSIONS: The results suggest that a usual dietary portion
      of the cola or chocolate used in this study would produce behaviorally
      discriminable plasma levels of caffeine in most subjects and of theobromine in at
      least one subject.

PMID- 9010707
TI  - Bioavailability of estradiol from a new matrix and a conventional reservoir-type
      transdermal therapeutic system.
AB  - OBJECTIVE: Bioavailability of estradiol delivered from a newly developed matrix
      type transdermal therapeutic system (MTTS) was compared with that of the
      conventional reservoir-type system (RTTS). Both formulations have a nominal
      delivery rate of 50 micrograms per day of 17 beta-estradiol (E2). Plasma
      concentrations of E2 and estrone (E1) were determined at steady state during a 96
      h application of each formulation to 34 postmenopausal volunteers, using a two
      stage randomized two-period crossover design. RESULTS: The MTTS proved to be
      equivalent to the RTTS with respect to the extent of E2 absorption. Due to
      differences in patch design and composition, the rate of absorption was different
      between the two systems, with less fluctuating E2 plasma levels during
      application of the matrix system. Local tolerability and adhesion of MTTS
      appeared to be better than those of the reservoir system.

PMID- 9010708
TI  - Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone.
AB  - OBJECTIVE: We studied the possible interaction between itraconazole, a potent
      inhibitor of CYP3A, and zopiclone, a short-acting hypnotic. METHODS: A double
      blind, randomized, two-phase crossover design was used. Ten healthy young
      subjects received daily either 200 mg itraconazole or placebo for 4 days. On day
      4 they ingested a single 7.5-mg oral dose of zopiclone. Plasma concentrations of
      zopiclone and itraconazole were determined and pharmacodynamic responses were
      measured up to 17 h. RESULTS: Itraconazole significantly increased the Cmax of
      zopiclone from 49 to 63 ng.ml-1. The t 1/2 of zopiclone was prolonged from 5.0 to
      7.0 h. The AUC(0-inifinity) of zopiclone was increased from 415 to 719 ng.ml-1 h
      by itraconazole. No statistically significant differences were observed in the
      pharmacodynamic responses between the groups. CONCLUSIONS: Itraconazole has a
      statistically significant pharmacokinetic interaction with zopiclone but this is
      only of limited clinical importance, at least in young adults.

PMID- 9010709
TI  - Effects of heat exposure in a Finnish sauna on the pharmacokinetics and
      metabolism of midazolam.
AB  - OBJECTIVE: The effect of short-term heat exposure in a Finnish sauna on hepatic
      first-pass metabolism and the capacity to metabolize midazolam were studied in a
      crossover trial. Midazolam oral (15 mg) and intravenous (0.05 mg.kg-1) was given
      to 6 healthy young male volunteers, in random order, during a control session and
      a sauna bathing session (temperature 85-100 degrees C, relative humidity 25-30%).
      Blood samples for the determination of plasma midazolam and alpha-hydroxy
      midazolam concentrations were taken for 6 h after drug administration. RESULTS:
      After oral administration, the bioavailability and clearance of midazolam were
      not affected by sauna bathing, nor was there a significant difference in alpha
      hydroxy midazolam plasma concentration or the alpha-hydroxy midazolam/midazolam
      AUC-ratio between the sessions. Midazolam Cmax was increased and its t1/2 beta
      was prolonged during the sauna session, but the clinical relevance of the
      findings appears to be modest. The pharmacokinetics of intravenous midazolam were
      not affected by sauna bathing. CONCLUSIONS: Short-term heat exposure may not
      affect the first-pass metabolism or hepatic capacity to metabolize midazolam.

PMID- 9010710
TI  - Lack of a pharmacokinetic interaction between moexipril and hydrochlorothiazide.
AB  - OBJECTIVE: To investigate the potential for pharmacokinetic interactions between
      moexipril, a new converting enzyme inhibitor, and hydrochlorothiazide after
      single dose administration. METHODS: 12 healthy male volunteers were studied by
      an open, randomised, three-way cross-over design, in which single doses of
      moexipril, hydrochlorothiazide and the two drugs together were administered.
      Blood and urine were collected up to 48 hours for measurement of the
      concentrations of moexipril and its metabolite moexiprilat. In addition, the
      urine samples were analysed for hydrochlorothiazide. RESULTS: For the area under
      the plasma concentration-time curve calculated from time 0 to a concentration
      greater than zero, AUC(O-t), the study showed a mean value of moexipril 437 ng.ml
      1.h-1 following administration of moexipril alone and 416 ng.ml-1.h-1 following
      moexipril concomitantly with hydrochlorothiazide. The corresponding values for
      the metabolite moexiprilat were 203 and 215 ng.ml-1.h-1, respectively. The Cmax
      of moexipril and the metabolite (data of the metabolite in parenthesis) were
      245.4 (70.8) ng.ml-1 after administration of moexipril alone and 241.0 (69.2)
      ng.ml-1 after coadministration of hydrochlorothiazide. The mean total renal
      excretion (TUE) of hydrochlorothiazide was 15.2 mg when administered alone and
      15.1 mg when given together with moexipril. The corresponding mean TUE-values for
      moexiprilat were 334 (1200) and 453 (1460) micrograms. CONCLUSIONS: The
      coadministration of moexipril with hydrochlorothiazide had no demonstrable effect
      on the measured pharmacokinetic parameters of moexipril, its active metabolite
      moexiprilat or hydrochlorothiazide.

PMID- 9010711
TI  - Influence of coronary artery bypass surgery on thyroid hormone parameters.
AB  - The postoperative period after cardiac surgery with cardiopulmonary bypass (CPB)
      is associated with a low T3 syndrome, i.e. low T3 and fT3 concentrations in the
      presence of normal T4 and TSH concentrations. So far, results from studies
      evaluating thyroid function during and after CPB are rather conflicting. We
      therefore evaluated prospectively thyroid function in 28 patients before, during
      and up to 3 days after coronary artery bypass surgery. We could demonstrate the
      most significant changes in thyroid hormone concentrations on day 1 after CPB
      (low T3 and fT3 concentrations, elevated rT3 concentrations in the presence of a
      significant fall of TSH). T3 fell from 1.93 to 0.6 nmol/1 and fT3 from 5.5 to
      1.42 pmol/1. Those patients with low cardiac output syndrome after surgery had
      significantly lower T3 concentrations than patients without this complication.
      Moreover, those patients, who already had significant lower T3 values prior to
      CPB, also demonstrated low T3 concentrations on day 1 after CPB. Cortisol usually
      has a suppressive effect on TSH secretion. However, the effect of cortisol on TSH
      in patients undergoing CPB seems to be not that important: those patients with
      high endogenous cortisol concentrations on day 1 after CPB had similar TSH values
      to those patients with only slightly elevated cortisol concentrations. Also, the
      application of high doses of catecholamines seems to have only minor effects on
      TSH secretion, because those patients requiring high doses of dopamine over a
      prolonged time period had essentially the same TSH values after CPB. Patients who
      had been exposed preoperatively to high doses of iodine did not demonstrate
      significantly different thyroid hormone concentrations. IN CONCLUSION: We could
      demonstrate that CPB induces a low T3 syndrome up to 3 days after surgery. Those
      patients with low T3 concentrations prior to surgery demonstrate postoperatively
      a more severe degree of nonthyroidal illness (NTI). Catecholamines and cortisol
      seem to have only minor effects on the TSH secretion after CPB. The influence of
      a previous iodine contamination is negligible.

PMID- 9010712
TI  - Hypothalamic-pituitary-adrenal function following cranial irradiation.
AB  - We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)
      adrenal function in 17 patients (12 females, 5 males) treated with cranial/
      craniospinal irradiation for acute leukemia (2 patients) or tumors distant from
      the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3
      rhabdomyosarcoma, 1 ependymoma). Estimated doses of radiation (RT) to the HP
      region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated
      with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at
      diagnosis and were studied at a median of 5 years (0.1-20 years) after RT.
      Patients received corticotropin-releasing factor (oCRF, 1 microgram/kg i.v.), and
      sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and
      120 min. The-5- and 0-min levels were combined for a standardized baseline value
      (Base). Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol
      response, were significantly lower in the patients. Twelve of seventeen patients'
      peak cortisol levels fell below the normal range. The patients' mean integrated
      values for cortisol (area under the curve) were not, however, different from
      controls. The ACTH responses to oCRF did not differ between patients and
      controls. No relationship was observed between ACTH or cortisol responses and the
      time elapsed from treatment or dose of HP RT. Further, in 10 of 12 patients, 0
      min dehydroepiandrosterone sulfate levels were lower than the expected normal
      mean levels for age, sex and pubertal status, and in 4 of these 10 patients the
      values were below the normal range. These data suggest that some patients treated
      with HP RT may be at risk for adrenal insufficiency.

PMID- 9010713
TI  - Growth pattern during the first 36 months of life in congenital adrenal
      hyperplasia (21-hydroxylase deficiency).
AB  - The longitudinal growth pattern during the first 36 months of life was studied in
      24 patients (17 females) with congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency by analyzing the mean required daily dose of cortisone
      with respect to steroid suppression, height and weight growth velocities and bone
      age maturation. All patients were treated with cortisone acetate and 9
      fluorohydrocortisone. The standard deviation score for length (SDS-L), the
      percentage of ideal body weight (% IBW) and biochemical parameters, 17-hydroxy
      progesterone (17-OHP) and androstenedione (A) were evaluated every 3 months; bone
      age (BA) was evaluated annually. At diagnosis, the female population of patients
      with respect to the males were younger (chronological age (CA): 15 +/- 14 vs. 45
      +/- 16 days, p < 0.005) and had a higher % IBW (91.7 +/- 8.0 vs. 76.3 +/- 16.7%,
      p < 0.05). At 3 months of age (45 days after initiating treatment) the % IBW in
      males normalized (97 +/- 19%) and was similar to that found in females (101 +/-
      12.8%). No differences were noted in SDS-L at the moment of diagnosis (females
      1.1 +/- 1.1 vs. males -0.5 +/- 0.7); however, at 3 months of age the SDS-L in
      females increased (0.41 +/- 0.88, p < 0.005 vs. diagnosis SDS-L) whereas that of
      males progressively decreased to reach the nadir at 6 months (-1.41 +/- 0.96). No
      differences between males and females were noted throughout this time with regard
      to: (a) A or 17-OHP levels (neither of which were suppressed to 'control
      values'); (b) the dosage of cortisone received (13.5-17.8 mg/m2/day), and (c)
      change in BA/CA ratio. In all patients the SDS-target height (TH) correlated with
      the SDS-L at 2 years (r = 0.74, p < 0.0005) and at 3 years (r = 0.60, p < 0.02)
      of age. In 12 patients who reached 7 years of age the SDS-L correlated with both
      SDS-predicted adult height (PAH) (r = 0.75, p < 0.001) and SDS-TH (r = 0.80, p <
      0.005). Although the commonly accepted definition of "good control' for patients
      with CAH has generally included, in addition to adequate suppression of hormone
      markers, normal growth and skeletal maturation, the present data suggest that
      normal growth and BA maturation are the most useful parameters to follow and not
      necessarily strive for hormone suppression. Early diagnosis and replacement
      therapy using cortisone doses less than those currently recommended allow normal
      growth within the genetic potential at least for the first 7 years of life.

PMID- 9010714
TI  - Molecular analysis of the androgen receptor gene in Kennedy's disease. Report of
      two families and review of the literature.
AB  - We have performed a molecular analysis of the androgen receptor gene in two
      families with suspected Kennedy's disease (spinal and bulbar muscular atrophy,
      SBMA) with the aim of making a firm diagnosis of the disease. The 2 patients
      studied were sporadic cases. Both presented clinical signs compatible with the
      diagnosis of SBMA: limb and facial muscular weakness of adult onset progressing
      toward muscular atrophy. Clinical signs of partial androgen insensitivity
      syndrome usually observed in SBMA were present only in patient 2. Enzymatic
      amplification of the CAG repeat region of exon 1 of the androgen receptor gene
      was performed on genomic DNA. PCR products were submitted to agarose or
      acrylamide electrophoresis for size evaluation. Precise determination of the CAG
      number was performed by direct sequencing of purified amplification products.
      Androgen receptor gene analysis was also performed in 2 sisters of patient 1 and
      in the mother, sisters and daughter of patient 2. Androgen receptor-binding
      activity was also determined on cultured genital skin fibroblasts of patient 1.
      Analysis of PCR products showed in both patients a single band that was much
      larger in size than the control. The expansion of the CAG repeat number was
      confirmed by direct sequencing: the exact number of CAG was 47 in patient 1 and
      42 in patient 2 (n = 12-32). The 2 studied sisters of patient 1 did not present
      the abnormal fragment, demonstrating they are not carriers for the disease.
      Conversely, the mother, sisters and daughter of patient 2 presented both normal
      and mutated alleles. The migration of the labelled PCR products on a sequencing
      gel revealed a meiotic instability of expanded CAG repeat in family 2. Moreover,
      patient 1 had a decreased androgen-binding capacity on cultured genital skin
      fibroblasts. In both families, analysis of the androgen receptor gene permitted
      us to diagnose SBMA in the patients and to establish the carrier status in
      siblings. These results correspond to the literature data and confirm the
      usefulness of CAG repeat evaluation in the diagnosis of Kennedy's disease. They
      highlight the relationship between the androgen receptor and motoneuron growth,
      development and regeneration.

PMID- 9010715
TI  - Urinary growth hormone excretion: results of a multicenter study in France.
AB  - Urinary growth hormone excretion (uGH), expressed as the average of three
      consecutive nocturnal measurements, was studied in 324 prepubertal and pubertal
      children without (n = 188) or with (n = 136) growth disorders. In prepubertal
      control children (n = 127), the mean uGH was 11.9 +/- 4.9 ng/l without any
      correlation with sex or age. During puberty, a significant increase of uGH was
      observed in both sexes (boys: prepubertal 12.3 +/- 4.84 vs. pubertal 16.2 +/- 4.7
      ng/l; girls: prepubertal 11.6 +/- 4.99 vs. pubertal 18.3 +/- 8.5 ng/l). In
      children with growth disorders, the results observed in various categories show a
      highly significant decrease in organic hypopituitary patients (p < 10(-6)) and
      obese subjects (p < 10(-6)) when compared to normal prepubertal children. In
      contrast, a significant increase was observed in 5 Laron-type dwarfisms (p < 10(
      6)). However, in 24 children with partial growth hormone deficiency assessed by
      blood measurements (two pharmacological tests between 5 and 10 ng/ml), the
      results were not significantly different from the controls (13.6 +/- 6.4 ng/l).
      In a group of 66 children with short stature and normal blood response to
      pharmacological tests, uGH concentrations were significantly higher than those of
      the control group (17.3 +/- 8.71 ng/l, p < 10(-6)). The data suggest that uGH
      measurements lead to findings comparable to blood measurements, avoiding the
      disturbance of pharmacological tests, in well-delimited categories of patients.
      In contrast, uGH measurements are not the best way to detect partial GH-deficient
      children, but may be used to screen partial peripheral GH resistance in children
      with nonendocrine short stature.

PMID- 9010716
TI  - Osmoregulation of plasma vasopressin in three cases with adrenal insufficiency of
      diverse etiologies.
AB  - Neurohypophyseal function was studied by hypertonic saline infusion with plasma
      vasopressin measurement in 3 patients with adrenal insufficiency before and after
      cortisol replacement. Although each patient had different causes of adrenal
      insufficiency, all showed impaired water excretion before replacement. The first
      patient with isolated adrenocorticotropin deficiency had marked hyponatremia and
      inappropriate vasopressin secretion which was normalized after replacement,
      indicating vasopressin hypersecretion during hypoadrenocorticism. The second
      patient had combined anterior and posterior pituitary deficiency due to
      postpartum hypopituitarism and showed completely absent vasopressin secretion,
      with her polyuria being masked before cortisol replacement, suggesting a
      vasopressin-independent intrarenal mechanism of antidiuresis. The third patient
      with panhypopituitarism due to a pituitary tumor also had preexisting diabetes
      insipidus with defective vasopressin secretion. In this case, however, plasma
      vasopressin was found to be elevated when adrenal insufficiency and hyponatremia
      subsequently developed. Together, these results indicate that vasopressin
      hypersecretion does occur during adrenal insufficiency, but that the accompanying
      urinary diluting defect may be attributable either to vasopressin-dependent or to
      vasopressin-independent mechanisms.

PMID- 9010717
TI  - The role of B7-1/B7-2:CD28/CLTA-4 pathways in the prevention of anergy, induction
      of productive immunity and down-regulation of the immune response.

PMID- 9010718
TI  - The role of CTLA-4 in the regulation and initiation of T-cell responses.

PMID- 9010719
TI  - CD80, CD86 and CD40 provide accessory signals in a multiple-step T-cell
      activation model.
AB  - In this review, a sequential multiple-step model for T-cell activation is
      proposed. In a series of in vitro studies, highly purified freshly isolated human
      peripheral blood T lymphocytes were stimulated through the CD28 receptor, with
      mAb or with natural ligands B7-1 or B7-2, along with TCR stimulation, in the
      absence of other costimulatory interactions. Ligation of the CD28 receptor, along
      with stimulation of the TCR, was found to up-regulate pleiotropic in vitro
      activities, including the secretion of both Th1 and Th2-type cytokines, B-cell
      help, and the development of cytotoxic activity. This costimulatory action
      involves CD4+ and CD8+ as well as naive and memory T-cell subsets. The expression
      of B7-1 and B7-2 on professional APC in situ in both normal and pathological
      tissues, and its up-regulation on monocytes by GM-CSF and IFN-gamma is consistent
      with this role. Additional studies have addressed the contribution of
      interactions between CD28 and B7-1 and B7-2 in T-cell activation initiated by
      normal un-engineered APC, such as stimulation with recall antigens and primary
      MLR. Blockade of the interaction between CD28 and B7-1/B7-2 under these
      conditions failed to completely inhibit T-cell responses or to induce anergy.
      Complete inhibition and anergy were, however, induced with a combination of CsA,
      targeting downstream TCR-triggered signalling, as well as anti-B7-1- and anti-B7
      2-directed reagents. Interestingly, and in contrast to anti-LFA-1 mAb, the
      addition of anti-B7-1 or anti-B7-2 reagents could be delayed until at least 48 h
      after the initiation of T-cell stimulation, indicating a requirement for a late
      interaction between CD28 and its counter-receptors. Interactions between CD40L on
      activated T cells and CD40 on APC may serve to sustain, enhance or prolong the
      presentation of B7-1 or B7-2 on the APC, and thus to prevent anergy induction, or
      ineffective or abortive T-cell stimulation. Based on these data a sequential
      multiple-step T-cell activation model is proposed, and novel strategies for
      immuno-intervention can be designed.

PMID- 9010720
TI  - The role of CD40 ligand in costimulation and T-cell activation.
AB  - It is clear by now that cell-to-cell interactions involving a variety of signals
      are required for effective immune response. The data reviewed here suggest that
      CD40-CD40L interactions are critical for development of CD4 T-cell-dependent
      effector functions. Lack of this important interaction results in greatly reduced
      activation of CD4 T cells, while successful interaction of these molecules
      results in full activation of these T cells. Consequently, the absence of CD40
      CD40L interactions leads to impairment of T-cell effector such as help for B-cell
      differentiation and class switch, activation of monocytes and macrophages to
      produce cytokines and to kill intracellular pathogens, and activation of
      autoreactive T cells to mount an autoimmune response. The effector functions of T
      cells controlled by CD40-CD40L interactions in a successful immune response are
      given in Table I. Data presented so far suggest that CD40-CD40L interactions play
      a role in early signalling events, where interactions of this kind are required
      to induce expression of costimulatory molecules on APC. One possible sequence of
      events in that APC, like DC, take up antigens at the site of injury or infection
      and migrate to lymph nodes, where they present antigens complexed with MHC class
      II molecules to naive T cells. This results in expression of CD40L on T cells.
      Coupling of this newly expressed CD40L on T cells with CD40 on APC results in
      expression of the costimulatory activity of the APC. At this time the
      costimulatory signal provided by the APC is received by the T cells via CD28/CTLA
      4, which drives the cell to enter into cell cycle and complete T cell activation.
      T cells thereby activated can now enter into secondary cognate CD40-CD40L
      dependent effector recognition with B cells to switch Ig class, macrophages to
      produce cytokines and new DC carrying the same antigen to up-regulate
      costimulatory activity. A tight regulation of expression of CD40L on T cells and
      costimulatory activity on APC would prevent activation of unwanted bystander T
      cells. The coupling of activation of the APC primed with the cognate antigen to
      the activation of the T-cell specific for that antigen in this model provides an
      additional regulatory step in the initiation of the immune response. This also
      suggests that a limited number of T cells/APC will be activated, both of which
      will be specific in nature. This additional step may be important for
      safeguarding against an autoimmune response. In addition, the fact that CD40L
      uniquely seems to play this role suggests that selective immunotherapies to treat
      autoimmune disease and prevent graft rejection can be targeted on this molecule.
      On the other hand, CD40-directed approaches to up-regulate costimulatory activity
      on APC could be developed to fight tumor growth, contain infections and treat
      immunodeficiencies.

PMID- 9010721
TI  - The role of CD2 as a regulator of human T-cell cytokine production.

PMID- 9010722
TI  - Regulation of signalling through B-lymphocyte antigen receptors by cell-cell
      interaction molecules.

PMID- 9010724
TI  - CTLA-4, a negative regulator of T-lymphocyte activation.

PMID- 9010723
TI  - The complexities of T-cell co-stimulation: CD28 and beyond.

PMID- 9010725
TI  - Surface expression of CD28 single chain Fv for costimulation by tumor cells.

PMID- 9010726
TI  - Expression of neu and Neu differentiation factor in the olfactory mucosa of rat.
AB  - The growth and differentiation of olfactory sensory neurons are regulated
      tightly. We had shown previously, by immunohistochemistry, that transforming
      growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) receptor are
      present in the olfactory epithelium of untreated adult rats and that TGF-alpha is
      a potent mitogen of olfactory epithelium in vitro. Expression of EGF receptor and
      TGF-alpha was detected primarily in horizontal basal cells and supporting cells
      but rarely in globose basal cells, which suggested that EGF receptor is not a
      likely candidate for the mitotic regulator of sensory neurons. In order to expand
      the search for candidate regulators, we have now examined other members of the
      EGF family of receptors and ligands. By utilizing reverse transcriptase
      polymerase chain reaction (RT-PCR) methodology, we have detected the messenger
      RNA encoding the protein of the neu gene (p185neu) and Neu differentiation factor
      (NDF) isoforms in the olfactory mucosa. Immunohistochemical localization of
      p185neu and NDF indicates expression of these proteins in the olfactory
      epithelium of adult rats in regions where globose basal cells and immature
      sensory neurons are found, as well as in the ensheathing cells of the olfactory
      nerve. The presence of neu and NDF transcripts in the olfactory tissue and the
      localization of their encoded polypeptides to proliferative regions of the
      epithelium suggest involvement of these gene products in the regulated
      proliferation/differntiation of the sensory neurons.

PMID- 9010727
TI  - LacZ and OMP are co-expressed during ontogeny and regeneration in olfactory
      receptor neurons of OMP promoter-lacZ transgenic mice.
AB  - The ontogeny and cellular specificity of expression of beta-galactosidase
      activity and olfactory marker protein (OMP) are compared in olfactory tissue of
      the H-OMP-lacZ-3 line of transgenic mice. In this line the expression of lacZ is
      driven by a 0.3 kb fragment of the rat OMP promoter. During fetal development,
      lacZ expression is detectable in olfactory receptor neurons (ORNs) shortly after
      the initial appearance of endogenous OMP. The beta-galactosidase marker was
      observed only in mature olfactory receptor neurons where it co-localized with
      endogenous OMP. It was absent from immature neurons that express the growth
      associated phosphoprotein B50/GAP43. Lesion of the peripheral olfactory pathway
      by intranasal irrigation with Triton X-100 eliminated expression of both OMP and
      lacZ in the olfactory neuroepithelium. Subsequent regeneration of the full
      complement of olfactory receptor neurons was associated with co-expression of
      both OMP and beta-galactosidase activity. Neither OMP nor beta-galactosidase
      activity was induced in any other cell type of the regenerating olfactory mucosa.
      Thus, as little as 0.3 kb of the OMP promoter has the ability to target lacZ
      expression to olfactory receptor neurons in a temporally and spatially defined
      manner. We discuss the potential utility of this transgenic line for future
      studies of the olfactory system.

PMID- 9010728
TI  - Characterization of olfactory receptor neurons and other cell types in
      dissociated rat olfactory cell cultures.
AB  - In dissociated cell cultures, control over the cellular environment facilitates
      study of the differentiation of mature cellular phenotypes. Central to this
      approach is a rigorous characterization of the cells that reside in culture.
      Therefore, we have used a battery of cell type-specific antibody markers to
      identify the cell types present in dissociated cultures of olfactory mucosal
      cells (containing cells from both the epithelium and lamina propria). To identify
      olfactory receptor neurons in the cultures, staining with antibodies against
      neuron-specific tubulin was compared to staining with antibodies to neuron
      specific enolase, the neural cell adhesion molecule, N-CAM, and the adhesion
      molecule, LI. Staining of mature olfactory neurons in culture, with an antibody
      against the olfactory marker protein, was compared to staining with antibodies to
      carnosine. In contrast to tissue section staining, the overlap between carnosine
      and olfactory marker protein staining was not complete. Olfactory nerve glial
      cells were immunoreactive for the S100 beta protein and nestin, an intermediate
      filament found in early neuronal progenitor cells and Schwann cells. Antibodies
      to nestin did not label olfactory neurons or progenitor cells. An antibody to an
      oligodendrocyte-Schwann cell enzyme, 2',3'-cyclic nucleotide 3'
      phosphodiesterase, did not label olfactory glia, but did label oligodendrocyte
      like cells that appeared to be derived from the CNS glial feeder layer. An
      antibody against the heavy (200 kDa) neurofilament protein stained a minor subset
      of cells. The cultures also contained muscle cells, cartilage cells and
      macrophages (and/or microglia). These results demonstrate that multiple cell
      types either maintain or re-establish differentiated, cell type-specific
      phenotypes in dissociated olfactory cell cultures.

PMID- 9010729
TI  - Olfactory epithelial organotypic slice cultures: a useful tool for investigating
      olfactory neural development.
AB  - An in vitro slice culture was established for investigating olfactory neural
      development. The olfactory epithelium was dissected from embryonic day 13 rats;
      400 microns slices were cultured for 5 days in serum-free medium on Millicell-CM
      membranes coated with different substrates. The slices were grown in the absence
      of their appropriate target, the olfactory bulb, or CNS derived glia. The
      cultures mimic many features of in vivo development. Cells in the olfactory
      epithelium slices differentiate into neurons that express olfactory marker
      protein (OMP). OMP-positive cells have the characteristic morphology of olfactory
      receptor neurons: a short dendrite and a single thin axon. The slices support
      robust axon outgrowth. In single-label experiments, many axons expressed neural
      specific tubulin, growth-associated protein 43 and OMP. Axons appeared to grow
      equally well on membranes coated with type I rat tail collagen, laminin or
      fibronectin. The cultures exhibit organotypic polarity with an apical side rich
      in olfactory neurons and a basal side supporting axon outgrowth. Numerous cells
      migrate out of the slices, of which a small minority was identified as neurons
      based on the expression of neural specific tubulin and HuD, a nuclear antigen,
      expressed exclusively in differentiated neurons. Most of the migrating cells,
      however, were positive for glial fibrillary acidic protein and S-100, indicating
      that they are differentiated glia. A subpopulation of these glial cells also
      expressed low-affinity nerve growth factor receptors, indicating that they are
      olfactory Schwann cells. Both migrating neurons and glia were frequently
      associated with axons growing out of the slice. In some cases, axons extended in
      advance of migrating cells. This suggests that olfactory receptor neurons in
      organotypic cultures require neither a pre-established glial/neuronal cellular
      terrain nor any target tissue for successful axon outgrowth. Organotypic
      olfactory epithelial slice cultures may be useful for investigating cellular and
      molecular mechanisms that regulate early olfactory development and function.

PMID- 9010730
TI  - Early olfactory fiber projections and cell migration into the rat telencephalon.
AB  - The formation and development of primary olfactory axons was studied in the rat
      embryo using acetylcholinesterase histochemistry, immunocytochemistry for neuron
      specific beta-tubulin (TuJ1) and growth associated protein 43 (GAP43), and a
      fluorescent tracer DiI. Olfactory axons extend from the olfactory receptor
      neurons localized in the olfactory epithelium. These fibers grow to reach and
      enter the olfactory bulbs, where they form the first relay and integrative
      synaptic station in the olfactory system: the olfactory glomerulus. In this
      communication we address the development of primary olfactory fibers: first from
      the olfactory placode and later from the olfactory epithelium. Olfactory fibers
      enter the olfactory bulbs apparently in a disordered manner but soon arrange
      themselves in hook shaped aggregates of fibers, with many boutons (immature
      synaptic terminals), to form the glomeruli. We detected this kind of structure
      for the first time at embryonic day 16. The olfactory receptor cells are usually
      anchored in the basal lamina of the olfactory epithelium but some of them, after
      reaching their targets, lose their epithelial attachment, leave the olfactory
      epithelium and migrate to and enter the olfactory bulbs. The traffic of cells
      between the olfactory epithelium and the brain lasts late into embryonic
      development. We describe four types of migratory mechanism used by different
      populations of cells to reach their targets in the telencephalic vesicle and
      propose the existence of migrating cells that enter the telencephalon. These data
      were corroborated by injections into the olfactory epithelium a of murine
      retrovirus carrying the Escherichia coli lac-Z gene.

PMID- 9010731
TI  - Essential role of thyroid hormones in maturation of olfactory receptor neurons:
      an immunocytochemical study of number and cytoarchitecture of OMP-positive cells
      in developing rats.
AB  - Neurogenesis and proliferation of olfactory receptor neurons (ORNs) in the
      olfactory epithelium (OE) are reduced in postnatal hypothyroid rats and
      upregulated following restoration of thyroid function, leading to compensatory
      growth and restitution of these deficits [Paternostro M.A. and Meisami E. (1993).
      Dev. Brain Res. 76, 151-161; Paternostro M.A. and Meisami E. (1994). Dev. Brain
      Res. 83, 151-162]. To investigate thyroid hormonal role on maturation of ORNs,
      serial sections of the septal OE from normal newborn, 25- and 90-day-old rats
      were immunostained for olfactory marker protein (OMP), a marker for mature ORNs,
      and compared with the same from age-matched hypothyroid rats and those allowed to
      recover from thyroid deficiency at the time of weaning (day 25). The parameters
      studied were the localization and distribution of the OMP(+) cells within the OE
      and their density and total number. Hypothyroidism was induced by adding the
      reversible goitrogen propylthiouracil (PTU) to the rats' drinking water (1 g/l)
      from birth to days 25 or 90. Recovery from hypothyroidism was induced by
      withdrawal of PTU at day 25. The OMP(+) cells occupied a distinct, broad band in
      the normal rat OE, while in hypothyroid animal, this band was narrow and
      restricted to OE's apical zones. Recovery resulted in broadening of the OMP(+)
      cell band and normalized distribution of OMP(+) cells as evident in the 90-day
      old recovery animals. In normal control rats, density of OMP(+) cells increased
      by 2.5- and 1.3-fold during the suckling and post-weaning period (days 25-90),
      while total numbers of these cells increased by 12- and 3-fold, respectively,
      during the same age periods. Hypothyroidism decreased the growth in density by 25
      and 30%, while total number of OMP(+) neurons were reduced by 40 and 70% in the
      25- and 90-day-old animals, respectively. Withdrawal of PTU resulted in marked
      restoration of these deficits so that, at 90 days, the total number of OMP(+)
      cells were only 20% less than 90-day-old controls. These results indicate that
      thyroid hormones are essential for maturation of single ORNs and accretion of new
      mature ORNs in the OE of suckling and post-weaning rat. Also, the process of
      maturation and the final number of mature ORNs show remarkable recovery from
      hypothyroid-induced growth retardation.

PMID- 9010732
TI  - The aging olfactory epithelium: neurogenesis, response to damage, and odorant
      induced activity.
AB  - Olfactory epithelium retains the capacity to recover anatomically after damage
      well into adult life and perhaps throughout its duration. None the less,
      olfactory dysfunctions have been reported widely for elderly humans. The present
      study investigates the effects of aging on the neurophysiological and anatomical
      status of the olfactory epithelium in barrier-raised Fischer 344X Brown Norway F1
      hybrid rats at 7, 10, 25 and 32/35 months old. The posterior part of the
      olfactory epithelium in 32/35-month-old rats is well preserved. Globose basal
      cells are dividing, and new neurons are being born even at this advanced age.
      None the less, the numbers of proliferating basal cells and immature, GAP-43 (+)
      neurons are significantly decreased. Neurophysiological status was evaluated
      using voltage-sensitive dye techniques to assess inherent patterns of odorant
      induced activity in the epithelium lining the septum and the medial surface of
      the turbinates. In middle and posterior zones of the epithelium, there were
      neither age-related changes in overall responsivity of this part of the olfactory
      epithelium to any of five odorants, nor shifts in the location of the odorant
      induced hotspots. The inherent activity patterns elicited by the different
      odorants do become more distinct as a function of age, which probably reflects
      the decline in immature neurons and a slight, but not statistically significant,
      increase in mature neurons as a function of age. In contrast with the excellent
      preservation of posterior epithelium, the epithelium lining the anterodorsal
      septum and the corresponding face of the turbinates is damaged in the 32/35-month
      old animals: in this part, horizontal basal cells are reactive, more basal cells
      and sustentacular cells are proliferating than in younger animals or in posterior
      epithelium of the same animals, and the neuronal population is less mature on
      average. Our findings indicate that degeneration of the olfactory epithelium is
      not an inevitable or pre-programmed consequence of the aging process, since the
      posterior zone of the epithelium is very well preserved in these barrier
      protected animals. However, the deterioration in the anterior epithelium suggests
      that environmental insults can accumulate or become more severe with age and
      overwhelm the regenerative capacity of the epithelium. Alternatively, the
      regenerative capacity of the epithelium may wane somewhat with age. Either of
      these mechanisms or some combination of them can account for the functional and
      anatomical deterioration of the sense of smell associated with senescence in
      humans.

PMID- 9010733
TI  - Development of 5'-nucleotidase staining in the olfactory bulbs of normal and
      naris-occluded rats.
AB  - The distribution of the adenosine-producing ecto-enzyme 5'-nucleotidase was
      investigated histochemically in the developing rat olfactory bulb. Rat pups
      underwent either unilateral surgical occlusion of the right external naris or
      sham surgery on postnatal day 1. At 10, 20, or 30 days postpartum, horizontal
      sections of the olfactory bulb were reacted histochemically to reveal the locus
      and intensity of 5'-nucleotidase activity. Relative staining levels were
      determined by optical densitometry in standardized bulb regions. A marked, age
      related increase in staining density was observed. Reaction product was found
      primarily in neuropil areas. The P10 and P20 control animals did not exhibit
      right/left differences in bulb staining; however, some laterality was observed in
      P30 animals. Inter-glomerular and regional variations were observed throughout
      the developmental period, including (1) differences between neighboring
      glomeruli; (2) a gradient in the dorsal-ventral axis of the bulb; and (3) a
      higher staining density in the medial-caudal portion of the bulb. In subjects
      with occluded nares, asymmetries in right/left bulb 5'-nucleotidase staining
      patterns were detected throughout development. Bulbs ipsilateral to the blocked
      nares exhibited increased staining density, suggesting that the procedure
      enhanced enzymatic activity. Understanding these variations in 5'-nucleotidase
      staining may be important for a complete understanding of the mechanisms of
      olfactory bulb maturation and may give insight into the possible role of this
      enzyme in synaptic malleability during nervous system development and
      regeneration.

PMID- 9010734
TI  - Early locus coeruleus lesions increase the density of beta-adrenergic receptors
      in the main olfactory bulb of rats.
AB  - Norepinephrine is supplied to both deep and superficial layers of the olfactory
      bulb through dense projections from the locus coeruleus. Beta-adrenergic
      receptors are located in nearly all bulb laminae, with high-density foci of beta
      1 and beta-2-adrenoceptors present in the glomerular layer. Early olfactory
      experiences that increase norepinephrine levels in the bulb also decrease the
      density of beta-1- and beta-2-adrenoceptors, as well as the number of high
      density glomerular foci of beta-2-receptors. Changes in bulb norepinephrine
      levels, therefore, may affect the density of beta-adrenoceptors in the bulb. In
      the current study, we test this hypothesis by performing unilateral lesions of
      the locus coeruleus with 6-hydroxydopamine on postnatal day 4, and examining the
      density of beta-1- and beta-2-adrenergic receptors in the main olfactory bulb of
      the rat using 125I-labeled iodopindolol receptor autoradiography on postnatal day
      19. Locus coeruleus destruction resulted in a statistically significant increase
      in the density of adrenergic receptors in the ipsilateral bulb compared to the
      contralateral bulb. Both beta-1- and beta-2-adrenoceptor subtypes increased in
      density with this manipulation, although the number of glomerular layer high
      density beta-2 foci was not significantly different between the two bulbs. These
      results are consistent with the hypothesis that changes in olfactory bulb
      norepinephrine can regulate the density of beta-adrenergic receptors in the bulb.

PMID- 9010735
TI  - Dopaminergic and GABAergic interneurons of the olfactory bulb are derived from
      the neonatal subventricular zone.
AB  - Earlier studies in our laboratory have demonstrated that a discrete region of the
      anterior part of the neonatal subventricular zone (SVZa) contains exclusively
      neuronal progenitor cells. The descendants of the SVZa progenitor cells are
      destined for the granule cell and glomerular layers of the olfactory bulb, where
      they differentiate into granule and periglomerular cells, the interneurons of the
      olfactory bulb, respectively. In the present set of experiments we examined the
      neurotransmitter phenotype of the SVZa-derived cells. In order to label SVZa
      derived cells, the cell proliferation marker bromodeoxyuridine (BrdU) was
      injected into the SVZa of postnatal day 2 (P2) rats. After 3 weeks, by which time
      most of the SVZa-derived cells have migrated to their final destination in the
      bulb, the animals were perfused and their brains processed for
      immunohistochemistry. To identify the neurotransmitter phenotype of the SVZa
      derived cells, sagittal sections of the forebrain, including the olfactory bulb,
      were double-labeled with an antibody to BrdU in conjunction with an antibody to
      gamma-amino-butyric acid (GABA) or tyrosine hydroxylase (TH), the rate limiting
      enzyme in the synthesis of dopamine. Using simultaneous indirect
      immunofluorescence to detect the presence of single- and double-labeled cells, we
      found that 59% and 51% of the BrdU-positive cells were immunoreactive for GABA in
      the granule cell and glomerular layers, respectively. In addition, 10% of the
      BrdU-positive periglomerular cells were immunoreactive for TH. The presence of
      double-labeled (BrdU-positive/GABA-positive and BrdU-positive/TH-positive) cells
      in the olfactory bulb, demonstrates that the SVZa is a source of the GABAergic
      and dopaminergic interneurons of the olfactory bulb during postnatal development.

PMID- 9010736
TI  - Neurogenesis in the olfactory bulb of the frog Xenopus laevis shows unique
      patterns during embryonic development and metamorphosis.
AB  - We determined the time of origin of neurons in the olfactory bulb of the South
      African clawed frog, Xenopus laevis. Tritiated thymidine injections were
      administered to frog embryos and tadpoles from gastrulation (stage 11/12) through
      metamorphosis (stage 65), paraffin sections were processed for autoradiography,
      and the distribution of heavily and lightly labeled cells was examined. In the
      ventral olfactory bulb, we observed that the mitral cells were born as early as
      stage 11/12 and continued to be generated through the end of metamorphosis.
      Interneurons (periglomerular and granule cells) were not born in the ventral bulb
      until stage 41, and birth of these cells also continued through metamorphosis.
      Labeled cells were observed in the accessory olfactory bulb, beginning at stage
      41. In contrast, the cells of the dorsal olfactory bulb were not born until the
      onset of metamorphosis (stage 54); at this stage in the dorsal bulb, the genesis
      of mitral cells, interneurons, and glial cells completely overlapped. The results
      indicate that olfactory axon innervation is not necessary to induce early stages
      of neurogenesis in the ventral olfactory bulb. On the other hand, the results on
      the dorsal olfactory bulb are consistent with the hypothesis that innervation
      from new or transformed sensory neurons in the principal cavity induces
      neurogenesis in the dorsal bulb.

PMID- 9010737
TI  - Immunohistochemical localization of laminin, fibronectin and collagen type IV in
      the nerve fiber layer of the olfactory bulb.
AB  - When the olfactory nerve is injured in adult mammals, the axons grow across the
      PNS-CNS transitional zone and re-innervate their synaptic contacts within the
      olfactory bulb. Some years ago, Liesi [Liesi P. (1985) Laminin-immunoreactive
      glia distinguish regenerative adult CNS systems from non-regenerative ones. EMBO
      J. 4, 2505-2511] reported the presence of laminin in non-basal lamina locations
      within the nerve fiber layer (NFL) of the olfactory bulb of adult rats and
      suggested that this molecule may facilitate olfactory axonal growth into and
      within the CNS. The purpose of the present study was to compare the expression of
      laminin, fibronectin, and collagen type IV in: (a) the NFL of developing and
      adult rats; and (b) the NFL rostral and caudal to a stab wound in the olfactory
      bulb of adult rats. Numerous punctate deposits of immunofluorescence were seen in
      the NFL of the E18 (Theiler stage 23) bulb when antisera to laminin, fibronectin
      or collagen type IV were used. There was a dramatic drop-off in staining at the
      border between the NFL and the presumptive glomerular layer. The staining pattern
      was similar in the newborn bulb, although the immunofluorescence was not as
      strong. In the unoperated adult rats, only laminin was present consistently as
      punctate deposits within the NFL, whereas all three antisera stained numerous
      punctate deposits within the NFL during the first week after a stab wound.
      Although there was a partial recapitulation of the expression pattern for
      laminin, fibronectin and collagen type IV in the lesioned adult NFL, it never
      reached the extent found in the E18 or newborn bulbs and its expression returned
      to normal levels prior to the re-innervation of the bulb during the second and
      third weeks after surgery. The results suggest that the molecular requirements
      for the successful growth of olfactory axons may differ during development to
      growth in adult animals.

PMID- 9010738
TI  - Developmental localization of GAP-43 and olfactory marker protein in rat
      olfactory bulb transplants.
AB  - In an effort to identify and understand the laminar disorganization that occurs
      in the transplanted (TX) rat olfactory bulb (OB), we examined the development of
      fiber systems within these TX OBs. One antibody for olfactory marker protein
      (OMP) was used to identify axons of mature olfactory receptor neurons (ONs) and a
      second antibody, for a growth-associated protein (GAP-43), provided a marker for
      all extending or immature fibers. Donor OBs were taken from fetuses on embryonic
      days 14 or 15 (sperm-positive day is zero) and TX directly into the cavity
      produced by removal of an OB in 1-day-old hosts of the same strain. After
      survival times of 1 and 2 weeks and at maturity, adjacent 8 microns paraffin
      sections from the TX material were examined for OMP and GAP-43 reactivity. Fiber
      bundles, reactive for OMP, were found within the TX by 1 week post-TX, indicating
      rapid re-innervation of the donor OB by ONs. The appearance of OMP reactivity
      gradually shifted from tightly packed, well-defined fiber bundles at 1 week post
      TX to a diffuse reticulated pattern of individual fibers emerging from bundles at
      maturity. The OMP-reactive fiber bundles of the TX OB also contained GAP-43
      reactive fibers, but GAP-43 reactivity also extended to other (OMP-negative)
      bundles and fields. Reactivity for GAP-43 in the TX OB was nearly ubiquitous at 2
      weeks post-TX but, as development progressed (in both the TX and normal OB), such
      reactivity gradually decreased. Thus, while maturation in sensory afferent fiber
      systems in the TX OB may be delayed, it eventually follows a pattern similar to
      that in the normal OB, suggesting that factors other than the timing of fiber
      extension may be responsible for the laminar disorganization of the TX OB.

PMID- 9010739
TI  - Regulation of c-Fos mRNA and fos protein expression in olfactory bulbs from
      unilaterally odor-deprived adult mice.
AB  - Odorant deprivation, produced by unilateral naris closure, profoundly reduces
      tyrosine hydroxylase (TH) expression within intrinsic olfactory bulb dopamine
      neurons. The TH gene contains an AP-1 site, which interacts with the product of
      the immediate early gene, c-fos. c-Fos exhibits activity dependent regulation in
      the CNS. The hypothesis that odorant stimulation and deprivation might modify c
      fos expression in TH neurons was tested in adult CD-1 mice, subjected to
      unilateral naris closure. After 2 months, naris closed and control mice were
      exposed to either clean air for 60 min or clean air for 60 min followed by 30 min
      of alternating exposure to 10% isoamyl acetate (1 min) and air (4 min). A
      parallel reduction occurred in TH and fos expression (both c-fos mRNA and fos
      like immunoreactivity) in the glomerular layer of the odorant-deprived olfactory
      bulb. Odor stimulation induced a short-lived increase in c-fos mRNA and fos-like
      immunoreactivity in olfactory bulbs contralateral to naris closure. The increase
      in fos expression was region-specific in the glomerular layer but more diffuse in
      mitral and granule cell layers. In olfactory bulbs ipsilateral to naris closure,
      odor stimulation also induced c-fos mRNA expression in the mitral and granule
      cell layers and sparsely within limited periglomerular regions. Odor induced
      expression in mitral and granule cell layers may represent increased centrifugal
      activity acting on as yet unknown genes. These results suggest a correlation
      between c-fos mRNA expression and increased neuronal activity in the olfactory
      bulb which, in turn, acts to regulate TH expression in periglomerular neurons.

PMID- 9010740
TI  - Activity blockade does not prevent the construction of olfactory glomeruli in the
      moth Manduca sexta.
AB  - During metamorphic development, the arrival at the olfactory (antennal) lobe of
      olfactory receptor axons initiates the process of glomerulus formation. The
      glomeruli are discrete spheroidal regions of neuropil that are the sites of
      synaptic interactions among receptor neurons and their target antennal-lobe
      neurons. The process of glomerulus formation begins as groups of receptor axons
      form protoglomeruli. These dense clusters of terminal branches mostly are
      discrete entities from the time they can be recognized, although a few branches
      from neighboring protoglomeruli overlap laterally. A previous study by Schweitzer
      et al. [Schweitzer E. S., Sanes J. R. and Hildebrand J. G. (1976) Ontogeny of
      electroantennogram responses in the moth, Manduca sexta. J. Insect Physiol. 22,
      955-960] has shown that odor-induced activity in the receptor neurons can be
      detected first in recordings from the axons in the antennal nerve only in the
      last few days of metamorphic development and thus could not influence the process
      of glomerulus formation. In this study, we have tested directly the possibility
      that an earlier presence of spontaneous activity in either the receptor axons or
      the antennal-lobe neurons could affect the process. Tetrodotoxin, a Na(+)-channel
      blocker, was injected into the hemolymph prior to the onset of glomerulus
      formation to block any spontaneous Na(+)-dependent activity. Subsequent
      intracellular recordings from antennal-lobe neurons revealed no spike activity.
      Comparison with vehicle-injected control animals at stages during and after
      glomerulus formation revealed no differences in the localization of receptor-axon
      terminal branches in the glomeruli, in the border of glial cells that forms
      around each glomerulus, or in the morphology of the tufted glomerular arbors of
      one of the antennal-lobe neurons. We conclude that: (1) the process of glomerulus
      formation is largely independent of activity; and (2) glomeruli as modular units
      of the CNS more closely resemble cortical barrels than cortical columns, both in
      their ontogeny and in the lack of an obvious effect of activity on the morphology
      of the neurons arborizing within them.

PMID- 9010741
TI  - Expression of the surface antigen A2B7 in adult and developing honeybee olfactory
      pathway.
AB  - In order to identify molecules involved in the development of the honeybee
      olfactory pathway, hybridoma technology has been used. Among different cell
      lines, A2B7 has been selected. It produces a specific antibody for a surface
      glycoprotein of 91 kDa. This protein is mainly expressed by both the antennal
      receptor cells and mushroom body neurons. Based on (i) the spatio-temporal
      pattern of expression during pupal development; (ii) the cell surface location of
      the antigen; and (iii) the partial molecular characterization of the antigen, a
      putative role for this protein in axonal fasciculation and guidance is discussed.

PMID- 9010742
TI  - The mind-body connection--anxiety, panic, mood and compulsion.

PMID- 9010743
TI  - Selective follicular reduction: what to do with the oocytes?
AB  - OBJECTIVE: To investigate the possible benefits of in vitro fertilization (IVF)
      of oocytes retrieved during selective follicular reduction of supernumerary
      follicles in non-IVF cycles. METHODS: Selective follicular reduction of
      supernumerary follicles was used to prevent ovarian hyperstimulation syndrome and
      multiple pregnancies in gonadotropin-stimulated cycles. We analyzed the data of
      13 cycles (13 women) retrospectively. RESULTS: Three pregnancies occurred in
      these 13 cycles (23%), one after intra-uterine insemination and two after timed
      coitus. In all cycles, oocytes were retrieved, and in 10 cycles fertilization was
      achieved (77%); in 6 cycles cryo-preservation was successful (46%) and in 3
      cycles embryo transfer (ET) was performed (23%). All embryos were of poor quality
      and no pregnancies occurred after ET of frozen-thawed embryos. The diagnostic
      value of fertilization failure seems to be low, since one of the patients who
      failed to show fertilization became spontaneously pregnant afterward. CONCLUSION:
      Based on our observations, the beneficial effect of IVF/cryopreservation during
      selective follicular reduction appears questionable.

PMID- 9010745
TI  - The successful use of hyperstimulated washed therapeutic donor insemination after
      standard therapeutic donor insemination has failed.
AB  - OBJECTIVE: To investigate whether an aggressive therapeutic donor insemination
      regimen (stimulated folliculogenesis and ovulation plus intrauterine
      insemination) can produce a better fecundability rate than a more traditional
      insemination regimen (non-stimulated folliculogenesis plus LH-timed intracervical
      insemination) in women who have failed to become pregnant during an initial
      series of six traditional insemination cycles. DESIGN: A retrospective comparison
      of fecundability rates was undertaken between women undergoing the traditional
      insemination protocol and those who voluntarily switched to ovarian
      hyperstimulation coupled with intrauterine insemination. PARTICIPANTS: Eight-two
      women who failed to become pregnant during an initial series of six intracervical
      insemination cycles. RESULTS: Fecundability was 5.6% in cycles of continued
      urinary LH-timed intracervical insemination and 19.4% when the more aggressive
      regimen was applied. The difference in fecundability between protocols was
      significant (P < .005). CONCLUSION: After an initial series of donor
      inseminations has failed, a more aggressive insemination regimen involving
      ovarian hyperstimulation followed by washed intrauterine insemination provides a
      higher fecundability rate than continued intracervical insemination.

PMID- 9010744
TI  - Effect of oral and transdermal hormone replacement therapy on lipid profile and
      Lp(a) level in menopausal women with hypercholesterolemia.
AB  - OBJECTIVE: The aim of this randomized clinical study was to evaluate the hormonal
      replacement therapy (HRT) effect on plasma lipoproteins and Lp(a) profile in 42
      menopausal women with primary hypercholesterolemia (total cholesterol > 240
      mg/dL). SETTING: University clinic. PATIENTS AND METHODS: 42 hypercholesterolemic
      menopausal women were randomly assigned to the following groups; (1) transdermal
      estradiol, 50 micrograms + medroxyprogesterone 10 mg/day for days; (2) conjugated
      equine estrogens, 0.625 mg/day + medroxyprogesterone acetate 10 mg/day for 12
      days; (3) no treatment. At baseline and after 3 and 6 months two blood samples
      were collected with a 24-hour interval in order to reduce intraindividual and
      laboratory variability. Serum total cholesterol, HDL cholesterol, triglycerides,
      LDL cholesterol, and Lp(a) were determined. RESULTS: Total cholesterol and LDL
      cholesterol significantly decreased after 6 months in both treated groups in
      comparison to untreated women; HDL cholesterol and triglycerides showed only
      minimal changes. HRT at the dosage utilized in the study did not seem influence
      the Lp(a) concentrations after 3 and 6 months. CONCLUSIONS: Both transdermal and
      oral estrogens at medium dosage have a favorable influence on total cholesterol
      and LDL-cholesterol level of hypercholesterolemic menopausal women, but Lp(a)
      remains resistant to manipulation.

PMID- 9010746
TI  - A comparative study of the effects of an estradiol-releasing vaginal ring
      combined with an oral gestagen versus transdermal estrogen combined with a
      levonorgestrel-releasing IUD: clinical findings and endometrial response.
AB  - OBJECTIVE: Our purpose was to compare the effects of a new estradiol-releasing
      vaginal ring with an oral progestin versus the efficacy, safety and acceptability
      of an intrauterine device releasing levonorgestrel combined with estradiol,
      delivered transdermally from a patch. Climacteric symptoms, bleeding pattern, and
      endometrial histologic features were studied. MATERIALS AND METHODS: Fifty-six
      parous, postmenopausal women with urogenital symptoms were allocated to two
      groups for 1 year" 28 women receiving estradiol by a vaginal ring (2 mg/3 months)
      and an oral progestin for 7 days every month and 28 women receiving a continuous
      transdermal daily dose of 50 micrograms of estradiol with a levonorgestrel
      releasing (20 micrograms/day) intrauterine device inserted. All the patients were
      subjected to vaginosonographic examination followed by thorough pathological
      examination of uterine curetting samples. RESULTS: A mean endometrial thickness
      (double layer) of 2.9 and 3.0 mm, respectively, was found to be predictive of
      normal endometrium. Both treatment regimens effectively relieved urogenital
      symptoms. Endometrial proliferation was not observed. CONCLUSIONS: Treatment of
      urogenital symptoms in postmenopausal women with these two forms of hormone
      replacement therapy was shown to be an effective and safe method, exhibiting
      possible advantages over other methods of treatment.

PMID- 9010747
TI  - Effect of sperm-agglutinating antibodies on sperm capacitation and acrosome
      reaction.
AB  - OBJECTIVE: To study the effect of polyclonal/monospecific antisera on sperm
      agglutination versus capacitation as well as acrosome reaction. MATERIALS AND
      METHODS: Swim-up spermatozoa from cauda epididymides of fertile male hamsters
      were incubated under liquid paraffin with polyclonal/monospecific antisera
      obtained from immunized BALB/C mice, as well as with normal serum from control
      BALB/C mice, at various dilutions. RESULTS: The anti-sperm antibodies caused a
      significant (P < .05) sperm agglutination of various types of dilutions below
      1:1000. Both capacitation and true acrosome reaction were inhibited significantly
      in the spermatozoa incubated with polyclonal/monospecific antisera. Capacitation
      in the spermatozoa with normal serum started earlier, i.e., at 2 hours of
      incubation compared to 3 hours of incubation in controls. CONCLUSION: The data
      differentiate the sperm agglutinating activity from anticapacitation and
      antiacrosome reaction activity of antisperm antisera at 1:1000 dilution.

PMID- 9010749
TI  - Crystallization and preliminary crystallographic studies of ribulose 1,5
      bisphosphate carboxylase/oxygenase from a red alga, Galdieria partita, with a
      high specificity factor.
AB  - Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) from a red alga,
      Galdieria partita, has been crystallized by the hanging drop vapor diffusion
      method. Two forms (Forms I and II) of crystals were obtained under distinct
      conditions. The Form I crystal belongs to monoclinic space group C2 with cell
      dimensions of a = 190.2, b = 140.0, c = 189.0 A, and beta = 102.6 degrees, and
      diffracts up to 3.0 A resolution. Diffraction from the Form II crystal was too
      weak to determine crystal data.

PMID- 9010748
TI  - Cellular and molecular physiology of Escherichia coli in the adaptation to
      aerobic environments.
AB  - Upon exposure to oxygen, Escherichia coli increases the expression of enzymes
      essential for aerobic respiration, such as components of the TCA cycle and
      terminal oxidase complexes. This increase requires the elimination of repression
      mediated by the Arc regulatory system under anaerobic conditions. Coordinately,
      the synthesis of enzymes that function in anaerobic processes such as
      fermentation decreases, partly due to the inactivation of the transcription
      factor Fnr. E. coli is thus able to adjust the levels of respiratory enzymes to
      fit its environmental circumstances, and in this case, reduces the production of
      the less energy efficient fermentation enzymes in favor of the aerobic pathways.
      In contrast to the advantage in energy production, aerobiosis brings a
      disadvantage to E. coli: the production of reactive oxygen species (ROS), i.e.
      superoxide anion radical (O2.-), hydrogen peroxide (H2O2), and hydroxyl radical
      (.OH). These byproducts of aerobic respiration damage many biological molecules,
      including DNA, proteins, and lipids. To alleviate the toxicity of these
      compounds, E. coli induces the synthesis of protective enzymes, such as Mn
      dependent superoxide dismutase (SodA) and catalase I (HP I), and this induction
      is controlled by the regulatory proteins SoxRS, OxyR, and ArcAB. Thus, ArcAB,
      Fnr, SoxRS, and OxyR function in concert so that E. coli can optimize its energy
      production and growth rate. Fnr and SoxRS are cytoplasmic, DNA-binding proteins,
      and these regulatory systems utilize iron-sulfur clusters as cofactors which may
      directly sense the redox environment. OxyR is also a cytoplasmic, DNA-binding
      protein, and appears to respond to redox potential through the oxidation state of
      a specific cysteine residue. In the ArcAB system (which belongs to the family of
      two-component regulatory systems), ArcB, a membrane protein, functions as the
      sensor, and ArcA, a DNA-binding protein, directly controls target gene
      expression. Under anaerobic conditions, ArcB undergoes autophosphorylation and
      transphosphorylates ArcA, stimulating ArcA's DNA-binding activity. During aerobic
      growth, the transphosphorylation of ArcA does not occur. In this signal
      transduction mechanism, the ArcB C-terminal or "receiver" domain plays a critical
      role; that is, it stimulates or abolishes the transphosphorylation depending on
      the metabolic state of the cell, which in turn is influenced by the availability
      of oxygen. E. coli thus employs at least four global regulatory systems which
      monitor the cellular oxidative/metabolic conditions, and adjust the expression of
      more than 70 operons to give the organism a better aerobic life.

PMID- 9010750
TI  - Dinuclear lanthanum(III) complex for efficient hydrolysis of RNA.
AB  - A dinuclear La3+ complex hydrolyzes the phosphodiester bond in diribonucleotides
      efficiently under mild conditions. The rate of hydrolysis is remarkably
      accelerated on the complex formation between La3+ and TPHP (TPHP = N,N,N',N'
      tetrakis [(2-pyridyl)methyl]-2-hydroxy-1,3-diaminopropane), and the highest
      activity is attained when the dinuclear structure is formed. The half-life of ApA
      hydrolysis by the dinuclear La3+ complex (1 mM) is 350 s, whereas that by the
      free La3+ ion (1 mM) is 23,000 s at pH 7.2 and 50 degrees C. The dinuclear La3+
      complex is promising as a catalytic center of artificial nucleases.

PMID- 9010751
TI  - Automated chemical synthesis of biologically active tRNA having a sequence
      corresponding to Ascaris suum mitochondrial tRNA(Met) toward NMR measurements.
AB  - RNA samples corresponding to Ascaris suum mitochondrial tRNA(Met) were chemically
      and automatically synthesized in amounts sufficient for NMR measurement.
      Conventional and rapid deprotection methods gave tRNA samples with the same amino
      acid-accepting activity as those prepared by other method; enzymatic synthesis,
      and enzymatic ligation of chemically synthesized fragments. The synthetic tRNA
      showed the same 1H-NMR spectrum in the iminoproton region as the ligated tRNA.
      This rapid and reliable preparation method thus provides biologically active tRNA
      for NMR measurement, and further, it is applicable for synthesis of other large
      synthetic RNAs, by combining the site-specific isotopic labeling method.

PMID- 9010752
TI  - Molecular cloning and characterization of a novel isoform of the human UDP
      galactose transporter, and of related complementary DNAs belonging to the
      nucleotide-sugar transporter gene family.
AB  - We described recently the molecular cloning of human UDP-galactose transporter 1
      (hUGT1) [Miura, N. et al. (1996) J. Biochem. 120, 236-241]. Now we have
      characterized its isoform, hUGT2, that is most likely generated through the
      alternative splicing of a transcript derived from the UGT genomic gene, that also
      codes for hUGT1. Introduction of the open reading frame sequence of hUGT2 into a
      mouse cell line, Had-1, that lacks the UDP-galactose transporter, complemented
      the genetic defect of the mutant, as judged from the lectin-sensitivity spectra
      of the transformants and the nucleotide-sugar transporting activity of microsomal
      vesicles isolated from them. UGT-related genes were found through a BLAST search
      of dbEST based on their significant similarity with hUGT genes. We report here
      cDNA clones belonging to two subfamilies of the nucleotide-sugar transporter gene
      family. One is the human CMP-sialic acid transporter gene, and the other is a
      group of homologous genes with an undefined function that are distributed in man,
      mouse, and rat, and show significant similarity to the yeast UDP-N
      acetylglucosamine transporter.

PMID- 9010753
TI  - Cloning and sequencing of mouse complementary DNA for heme oxygenase-2.
AB  - A mouse cDNA encoding a human homologue of heme oxygenase-2 (HO-2) was isolated.
      The deduced protein contains 315 amino acids and has a calculated molecular mass
      of 35.8 kDa. The nucleotide sequence is 85.6% identical and the amino acid
      sequence 87% identical to those of the human protein. The corresponding mRNA is
      present in brain and testis, but not in ovary, kidney, liver, or spleen.

PMID- 9010754
TI  - N-terminal processing and amino acid sequence of two isoforms of nitric oxide
      reductase cytochrome P450nor from Fusarium oxysporum.
AB  - Cytochrome P450nor (P450nor), a nitric oxide reductase involved in the
      denitrifying system of the fungus Fusarium oxysporum, revealed molecular
      multiplicity. Two isoforms of P450nor, termed P450norA (norA) and P450norB
      (norB), were isolated. They had distinct isoelectric points of 5.1 (norA) and 4.9
      (norB). However, their catalytic, spectroscopic, and immunological properties
      were almost identical. Partial amino acid sequences, involving 263 amino acid
      residues of norA and 278 residues of norB among 404 and 402 residues,
      respectively, were determined. Corresponding sequences in the isoforms were
      identical, and all of the determined partial sequences of norA or norB coincided
      with the sequence deduced from the CYP 55 gene or its cDNA. The amino acid
      sequence determination ruled out the possibility that there is a redox center in
      P450nor derived from amino acid residues, e.g., quinonoid cofactors. The only
      difference between norA and norB was in their N-termini. The N-terminus of norA
      was a threonine residue, whereas that of norB was an N-acetylated alanyl residue
      and norB was shorter by 2 residues than norA. The results suggested that norA and
      norB may be the products of the same gene, but translated from different
      initiation codons. The hypothetical precursor of norA would have a presequence
      containing targeting and sorting signals for transportation to the intermembrane
      space of mitochondria. This is consistent with the results of a Western-blot
      analysis which showed that norA was recovered only in particulate fractions,
      whereas norB was in the soluble fraction. It is therefore likely that the
      intracellular localizations as well as the N-termini of norA and norB are
      different, owing to the differences in the translational initiation codons and
      co/post-translational processings.

PMID- 9010755
TI  - Biosynthetic transport of a major lysosome-associated membrane glycoprotein 2,
      lamp-2: a significant fraction of newly synthesized lamp-2 is delivered to
      lysosomes by way of early endosomes.
AB  - Lysosomal membranes contain two highly glycosylated proteins, designated as lamp
      1 and lamp-2, as major components. Lamp-1 and lamp-2 are similar to each other in
      the protein structure. Here, we investigated the biosynthetic transport of lamp-2
      through the endocytic vacuoles in cultured rat hepatocytes in comparison with
      that of lamp-1, which has previously been studied [Akasaki et al. (1995) Exp.
      Cell Res. 220, 464-473]. Newly synthesized lamp-2 (NS-lamp-2) was transported to
      the trans-Golgi from rough endoplasmic reticulum with a half time (t1/2) of 32
      min, more slowly than NS-lamp-1 (t1/2 = 13 min). After leaving the trans-Golgi,
      NS-lamp-2 is transferred to at least three compartments; the cell surface (t1/2 =
      47 min), cell peripheral early endosomes (t1/2 = 38 min) and perinuclear late
      endosomes (t1/2 = 48 min). NS-lamp-2 transported to any compartment is delivered
      finally to lysosomes (t1/2 = 90 min). A significant fraction of NS-lamp-2 (45% of
      the total) was transported from the trans-Golgi to early endosomes, and then
      delivered to dense lysosomes via perinuclear late endosomes, whereas a major
      portion of NS-lamp-1 follows an intracellular route to late endosomes without
      passing through the cell periphery. NS-lamp-2 leaves the cell peripheral region
      more rapidly than NS-lamp-1. The kinetic and quantitative data for biosynthetic
      transport of NS-lamp-2 to early endosomes and the cell surface indicate that NS
      lamp-2 may be transported first to early endosomes, from which a small portion of
      it (approximately 3.5% of the total) moves to the plasma membrane via a recycling
      system. In contrast, a small fraction of NS-lamp-1 is transported to the plasma
      membrane directly from the trans-Golgi, since NS-lamp-1 is delivered to the
      plasma membrane and early endosomes with almost the same half times.

PMID- 9010757
TI  - Effects of subtilisin cleavage of monomeric actin on its nucleotide binding.
AB  - The kinetics of ATP exchange on subtilisin-cleaved G-actin was investigated by
      measuring the fluorescence of 1,N6-ethenoadenosine 5'-triphosphate. The apparent
      dissociation rate of ATP (k-ATP) was 2.8-fold larger than that of intact G-actin
      in the presence of 300 microM free Ca2+. Analysis of the dependence of k-ATP on
      free Ca2+ showed that the dissociation rate constant of tightly bound Ca2+ was
      not significantly changed by subtilisin cleavage. On the other hand, an
      equilibrium binding study using 8-amino-2-[(2-amino-5-methylphenoxy)-methyl]-6
      methoxyquinoline N,N,N',N'-tetraacetic acid (Quin 2) showed that the affinity of
      tightly bound Ca2+ for G-actin was reduced by about 13-fold after subtilisin
      treatment. Consequently, the stabilization by Ca2+ of ATP was weak in cleaved G
      actin. Furthermore, the kinetic analysis of ATP exchange revealed that the
      binding equilibrium between ATP and divalent cation-free cleaved G-actin was much
      slower than that in the case of intact G-actin.

PMID- 9010756
TI  - Complete nucleotide sequences of the genes encoding translation elongation
      factors 1 alpha and 2 from a microsporidian parasite, Glugea plecoglossi:
      implications for the deepest branching of eukaryotes.
AB  - Complete nucleotide sequences of the genes putatively encoding translation
      elongation factors 1 alpha (EF-1 alpha) and 2 (EF-2) from a mitochondrion-lacking
      protozoan, Glugea plecoglossi, that belongs to microsporidians were determined.
      The deduced amino acid sequences of the putative EF-1 alpha and EF-2 of Gl.
      plecoglossi showed very unusual features compared with typical eukaryotic
      sequences. The degree of divergence was especially great in the EF-1 alpha
      sequence, although it clearly showed a eukaryotic feature when aligned with
      homologs from the three primary kingdoms. Phylogenetic analyses of EF-1 alpha and
      EF-2 on the basis of the maximum likelihood method of protein phylogeny clearly
      and consistently suggested that among eukaryotic species being analyzed, Gl.
      plecoglossi and another mitochondrion-lacking protozoan, Giardia lamblia,
      respectively represent the earliest and the second earliest offshoots of
      eukaryotes. When the EF-1 alpha and EF-2 phylogenies were totally evaluated, the
      earliest divergence of Gl. plecoglossi in eukaryotes became more clearly
      confirmed. If the phylogenetic relationship inferred from the present analysis
      are correct, microsporidians might be extremely ancient eukaryotes that diverged
      before the occurrence of mitochondrial symbiosis.

PMID- 9010758
TI  - Dipeptidyl peptidase IV from Xanthomonas maltophilia: sequencing and expression
      of the enzyme gene and characterization of the expressed enzyme.
AB  - The dipeptidyl peptidase IV [EC 3.4.14.5] gene of Xanthomonas maltophilia,
      expressed in Escherichia coli, was cloned by the shotgun method. Nucleotide
      sequence analysis revealed an open reading frame of 2,223 bp, coding for a
      protein of 741 amino acids with a predicted molecular weight of 82,080. The
      expressed enzyme was extracted with SDS, and the solubilized enzyme was purified
      about 1,030-fold on columns of Toyopearl HW65C, DEAE-Toyopearl twice, and
      hydroxyapatite, with an activity recovery of 50%. The enzyme hydrolyzed a proline
      containing peptide at the penultimate position, and was inhibited by diisopropyl
      phosphofluoridate. The enzyme was most active at pH 8.5, and was stable between
      at pH 7.0 and 9.0. The molecular weight of the purified enzyme was estimated to
      be 83,000 and 165,000 by SDS-PAGE and gel filtration, respectively.

PMID- 9010759
TI  - Inhibition of G1 cyclin expression in normal rat kidney cells by inostamycin, a
      phosphatidylinositol synthesis inhibitor.
AB  - We previously reported that inostamycin, an inhibitor of CDP-DG: inositol
      transferase, inhibited cell proliferation in normal rat kidney (NRK) cells by
      blocking cell cycle progression at the G1 phase. In the present paper, we report
      the effect of inostamycin on the serum-induced activation of Ser/Thr protein
      kinases that are involved in G1 progression. In quiescent NRK cells mitogen
      activated protein kinase (MAP kinase) and casein kinase II were activated within
      15 min after serum addition. Neither activation was affected by the treatment
      with inostamycin. However, in the inostamycin-treated cell, cyclin-dependent
      kinase 2 (CDK2) failed to be activated after serum stimulation. Since serum
      induced expression of cyclin E was also suppressed by inostamycin, this inhibitor
      would appear to block CDK2 activation by inhibiting cyclin E expression.
      Furthermore, inostamycin also inhibited cyclin D1 expression induced by serum;
      and consequently, hyperphosphorylation of retinoblastoma protein (pRB) by RB
      kinases such as CDK4 and CDK2 was abolished, which would result in elimination of
      functional inactivation of pRB. Thus, early G1 arrest in NRK cells by inostamycin
      is due to the inhibition of cyclin D1 and E expressions.

PMID- 9010760
TI  - Fine substrate specificities of four exo-type cellulases produced by Aspergillus
      niger, Trichoderma reesei, and Irpex lacteus on (1-->3), (1-->4)-beta-D-glucans
      and xyloglucan.
AB  - To investigate the fine substrate specificities of four highly purified exo-type
      cellulases (Exo-A from Aspergillus niger, CBHI and CBHII from Trichoderma reesei,
      and Ex-1 from Irpex lacteus), water-soluble substrates such as barley glucan,
      xyloglucan from tamarind (Tamarindus indica L.), and their oligosaccharides were
      employed. Four exo-type cellulases immediately hydrolyzed 3-O-beta-D
      cellotriosylglucose to produce cellobiose and laminaribiose. In contrast, CBHII
      showed no hydrolytic activity towards 3(2)-O-beta-D-cello-biosylcellobiose, which
      was hydrolyzed to cellobiose by the other exo-type cellulases. These cellulases
      hydrolyzed the internal linkages of barley glucan and lichenan in an endo-type
      fashion to produce cellobiose and mix-linked oligosaccharides as main products.
      The DP-lowering activities of the four exo-type cellulases on barley glucan were
      in the order of Ex-1, CBHII, Exo-A, and CBHI. Based on gel permeation
      chromatography analysis of the hydrolysates, Ex-1 seemed to attack the internal
      cellobiosyl unit adjacent to beta-1,3-glucosidic linkages in barley glucan
      molecule more frequently than did the other cellulases. Xyloglucan was hydrolyzed
      only by CBHI and CBHII, and produced hepta-, octa-, and nona-saccharides. In
      addition, a xyloglucan tetradecasaccharide (XG14) was split only to
      heptasaccharide (XG7) by CBHI and CBHII.

PMID- 9010761
TI  - Selective interaction of synthetic antimicrobial peptides derived from sapecin B
      with lipid bilayers.
AB  - By measuring carboxyfluorescein leakage from liposomes and the increase in
      membrane current through planar lipid bilayer membranes, we examined the
      capacities of a series of low-molecular-weight cationic amphiphilic peptides
      derived from the alpha-helix domain of sapecin B for membrane-perturbation and
      ion-channel formation. Some of these peptides strongly interact with membranes
      containing acidic phospholipids and phosphatidylethanolamine, with a very
      negative potential, which are characteristic of the Escherichia coli membrane, in
      parallel with their antimicrobial activity. In contrast, they do not interact
      with membranes which predominantly contain choline phospholipids and cholesterol
      in their outer leaflets, with a slightly negative potential, all of which are
      characteristic of eukaryotic membranes, thereby providing a molecular basis for
      their selective toxicity. Membranes doped with these peptides are as permeable to
      inorganic phosphates as to chloride ions and are far more permeable to cations.
      The loss of inorganic phosphates may damage bacterial cells due to rapid
      depletion of cytoplasmic ATP. Examination of the structure-activity relationships
      of a series of derived peptides in their interaction with a model of the E. coli
      membrane confirmed the necessity of cationic amphiphilicity for the peptides to
      attack the bacterial membrane and to exhibit antimicrobial activity.

PMID- 9010762
TI  - Effects of methionine and Cu2+ on the expression of tyrosinase activity in
      Streptomyces castaneoglobisporus.
AB  - Streptomyces castaneoglobisporus HUT6202 expresses an enzyme, tyrosinase,
      responsible for the production of melanin-like pigments. The present study
      revealed that the tyrosinase synthesis by the microorganism was induced about 80
      fold, when young cells cultured for 6 h were incubated with methionine (Met) to
      the mid-log phase of growth, in comparison to without this amino acid. The Met
      induced tyrosinase synthesis was inhibited by the addition of rifampicin and
      chloramphenicol, suggesting that transcriptional and translational events are
      necessary for the induction. We found that the addition of Cu2+ to the culture
      medium brings forward the period of expression of Met-induced tyrosinase
      activity.

PMID- 9010763
TI  - Determination of the affinity constants of pea lectin for neutral sugars by
      capillary affinophoresis with a monoligand affinophore.
AB  - Affinophoresis is a type of affinity electrophoresis in which an affinophore, a
      conjugate of an affinity ligand and a multiply charged soluble matrix, causes a
      change in migration velocity of proteins which have a specific affinity for the
      ligand. A monoligand affinophore bearing a mannoside was prepared by coupling
      iodoacetylated p-aminophenyl alpha-D-mannoside to the free thiol group of N
      succinylated glutathione, and used for the affinophoresis of pea lectin in a
      capillary. The electrophoretic mobility of pea lectin towards the anode increased
      in the presence of the affinophore as a function of its concentration in a manner
      that is described by the equation for affinity electrophoresis. Analysis of the
      suppression of the affinophoresis on the addition of neutral sugars to the system
      allowed the determination of the dissociation constants of the lectin for these
      neutral sugars. The dissociation constants obtained on affinophoresis agreed well
      with the values in the literature. The preparation of a monoligand affinophore
      for ligands bearing an amino group should facilitate the application of this type
      of microscale analysis (0.14 ng of protein for each run) to protein ligand
      interactions.

PMID- 9010764
TI  - Glycation decreases the stability of the triple-helical strands of fibrous
      collagen against proteolytic degradation by pepsin in a specific temperature
      range.
AB  - When fibrous collagen of rat tail tendons was glycated by incubation with ribose,
      it became highly insoluble in dilute acetic acid and resistant to pepsin
      digestion at 5 degrees C, since it was cross-linked by advanced glycation end
      products. Extensively glycated fibrous collagen was found to be much less stable
      than non-glycated control fibrous collagen against pepsin digestion at 30 degrees
      C. Under conditions where nearly all of the glycated fibrous collagen was
      degraded into small peptides by pepsin, approximately 45% of the control collagen
      was left as large polypeptides having nearly the whole length of its triple
      helical region. A soluble collagen, which consisted primarily of the triple
      helical region of monomeric collagen, was found to be glycated as efficiently as
      the fibrous collagen on incubation with ribose at 30 degrees C, while the rate of
      cross-linking of the soluble collagen was very low, suggesting that the triple
      helical strands do not undergo intramolecular cross-linking and that most of the
      cross-links produced in the glycated fibrous collagen are intermolecular ones.
      The glycated soluble collagen was as stable as the control collagen against
      pepsin digestion at 30 degrees C. These results indicate that the triple-helical
      strands of glycated fibrous collagen are much less stable than those of the non
      glycated form against proteolytic digestion by pepsin at a temperature close to
      but below their melting point. Sugar-derived intermolecular cross-links are
      supposed to underly the decreased stability of the triple-helical strands.

PMID- 9010765
TI  - Role of basic amino acids in the cleavage of synthetic peptide substrates by
      mitochondrial processing peptidase.
AB  - Our recent experiments using model peptides of rat malate dehydrogenase (MDH)
      indicated that a proximal arginine and a distal basic amino acid are important
      for processing by mitochondrial processing peptidase (MPP). [Niidome, T., Kitada,
      S., Shimokata, K., Ogishima, T., and Ito, A. (1994) J. Biol. Chem. 269, 24719
      24722]. To elucidate if the recognition elements apply to other precursor
      proteins, we analyzed cleavage of model peptides of human ornithine
      aminotransferase (OAT). Purified peptidase cleaved peptides that corresponded to
      N-terminal 1-25 and 3-25 at the correct site (Gly17-Val18) at nearly equal rates.
      Replacement of Arg16 (-2 position) with lysine or alanine reduced the processing
      efficiency by 95- and 380-fold, respectively. Either deletion from Met1 to Arg10
      or replacement of the basic amino acids between them decreased the processing
      efficiency considerably. A peptide containing Arg7 in addition to Lys4 and Arg10
      was more effective than the control peptide. However, a peptide with one and two
      consecutive basic amino acids in the distal region had a processing efficiency
      close to the control peptide. These results indicated that processing of OAT was
      enhanced by an increase in the number of basic amino acids with a suitable
      distance between them. In other respects, the processing signal of OAT was
      essentially the same as that of MDH.

PMID- 9010766
TI  - Cloning and sequencing of cDNAs encoding plasma alpha-macroglobulin and
      murinoglobulin from guinea pig: implications for molecular evolution of alpha
      macroglobulin family.
AB  - Several clones encoding plasma alpha-macroglobulin and murinoglobulin were
      isolated from guinea pig liver cDNA library and sequenced. The clones for alpha
      macroglobulin contained overlapping sequences which together spanned a stretch of
      4,546 nucleotides with one open reading frame coding for 1,476 amino acid
      residues. The clones for murinoglobulin contained overlapping sequences which
      together spanned a stretch of 4,578 nucleotides with one open reading frame
      coding for 1,464 amino acid residues. The phylogenetic analyses of 11 proteins of
      the alpha-macroglobulin family revealed that the mammalian tetrameric alpha
      macroglobulins consist of two main branches: alpha M-1 subfamily (rat alpha 1-
      and mouse alpha-macroglobulins) and alpha M-2 subfamily (human alpha 2-, rat
      alpha 2-, and guinea pig alpha-macroglobulins). This dichotomy is in good
      accordance with their immunological, chemical, and physicochemical properties,
      and indicates that guinea pig alpha-macroglobulin is orthologous to human and rat
      alpha 2-macroglobulins but paralogous to rat alpha 1- and mouse alpha
      macroglobulins. The divergence of the two subfamilies was a phylogenetically
      ancient event which occurred around the separation of metatherians and
      eutherians. The genes of the two subfamilies have been maintained in the rat, but
      either one became extinct in the mouse, guinea pig, or human. The tree also shows
      that guinea pig murinoglobulin forms one clade with mouse and rat murinoglobulins
      (alpha 1-inhibitor 3) prior to joining the alpha M-2 lineage, and suggests that
      murinoglobulin is not a primitive form of tetrameric alpha-macroglobulin, but
      rather has evolved under selective pressure which is different from that of the
      tetrameric paralogues.

PMID- 9010767
TI  - Comparison of ncd and kinesin motor domains by circular dichroism spectroscopy.
AB  - ncd is a microtubule motor protein from Drosophila, having a 40 kDa domain
      homologous to the kinesin motor domain. In the present study, we investigated the
      circular dichroism (CD) spectra of the ncd motor domain in comparison with those
      of the kinesin motor domain. Although the two are about 40% identical in amino
      acid sequence, and recent X-ray crystallographic studies [Sablin, Kull, Cooke,
      Vale, and Fletterick (1996) Nature 380, 555-559; Kull, Sablin, Lau, Fletterick,
      and Vale (1996) Nature 380, 550-555] indicate that their core structures are
      nearly identical, the far UV CD spectra of ncd and kinesin motor domains, both
      being monomeric, were considerably different from each other, suggesting a
      significant difference in the secondary, especially loop structures. The motor
      domain of ncd, like that of kinesin, contains tightly associating ADP even after
      purification. We removed ADP from the ncd motor domain by gel filtration in the
      presence of EDTA and high salt. The resultant protein, however, was likely to be
      in an inactive state, since it bound ATP slowly. The far UV CD spectrum of the
      ncd motor domain devoid of ADP was nearly identical to that of the ncd motor
      domain with bound ADP. This indicated that the removal of ADP did not affect the
      backbone structure in the presence of high salt. On the other hand, the near UV
      CD spectrum of the ADP-free ncd motor domain differed from that of the ncd motor
      domain. ADP complex, one possibility being that the local conformation was
      changed upon removal of bound ADP. The near UV CD spectra of kinesin motor domain
      also showed a difference between the ADP-bound form and the nucleotide-free form,
      although the difference was much smaller.

PMID- 9010768
TI  - Isolation and expression of a Xenopus laevis DNA methyltransferase cDNA.
AB  - A Xenopus DNA methyltransferase cDNA was isolated from a Xenopus oocyte cDNA
      library by screening with the mouse DNA methyltransferase cDNA as a probe. The
      elucidated nucleotide sequence gave a 4,470 nucleotide open reading frame, and
      the predicted protein was composed of 1,490 amino acid residues, showing high
      homology to animal DNA methyltransferases, especially in the catalytic domain in
      the carboxyl-terminal region. The cysteine-rich region and the Lys-Gly repeat
      which were first found in the mouse sequence were conserved in Xenopus. However,
      200 amino acid residues at the amino-terminus of Xenopus DNA methyltransferase
      were quite different from those of mouse and human, but showed 70% homology with
      those of chicken. The cloned Xenopus DNA methyltransferase cDNA expressed in COS1
      cells showed a significant DNA methyltransferase activity. The size of the
      translation product of Xenopus DNA methyltransferase cDNA expressed in COS1 cells
      was identical with that of the endogenous DNA methyltransferase in Xenopus A6
      cells and also with the size of newly synthesized DNA methyltransferase in
      Xenopus oocytes. However, a slightly larger immunoreactive band of about 205 kDa,
      and a small immunoreactive band of about 100 kDa, which were poorly labeled by
      short incubation with radiolabeled amino acids, were the main bands in stage I
      III and stage IV-VI oocytes, respectively.

PMID- 9010769
TI  - Role of calcium in tumor necrosis factor-alpha production by activated
      macrophages.
AB  - The role of calcium in the production of tumor necrosis factor-alpha (TNF-alpha)
      by the lipopolysaccharide (LPS)-stimulated macrophage cell line, J774.1, was
      investigated. Flow cytometric measurement of intracellular calcium concentration
      ([Ca]i) using 2-(3,6-bis(acetyl-oxy)-2,7-dichloro-9H-xanthen-9-yl)benzoic acid
      (fluo-3)-loaded J774.1 cells revealed that LPS at more than 0.1 microgram/ml
      increased [Ca]i transiently in the presence or absence of serum, and that a
      mixture of a calcium chelator, ethyleneglycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid (EGTA), and a calcium release blocker from
      intracellular store sites, 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate
      hydrochloride (TMB-8), inhibited the [Ca]i response induced by LPS. In
      concordance with this, production of TNF-alpha was inhibited by EGTA and/or TMB
      8. These reagents also reduced the level of TNF-alpha mRNA significantly. These
      results indicate that the transient increase of [Ca]i plays a role in LPS-induced
      expression of TNF-alpha by the macrophage cell line.

PMID- 9010770
TI  - Differential expression of laminin-5/ladsin subunits in human tissues and cancer
      cell lines and their induction by tumor promoter and growth factors.
AB  - We previously reported a new laminin variant containing laminin gamma 2 (or B2t)
      chain, ladsin, which exerted prominent cell-scattering, cell-adhesion, and cell
      migration activities. In the present study, this laminin was further
      characterized, and gene expression of its three subunits in various human tissues
      and cancer cell lines was examined by Northern blotting. cDNA cloning of the
      largest subunit of ladsin and partial amino acid sequencing of its beta (or B1)
      subunit revealed that ladsin was identical to laminin-5 (kalinin/epiligrin/
      nicein). Among various human tissues, placenta, lung, and fetal kidney expressed
      high levels of mRNAs for the three subunits of laminin-5 (laminin alpha 3EPA,
      beta 3, and gamma 2 chains). Most gastric and squamous carcinoma cell lines
      constitutively expressed all of the three subunit mRNAs, while other types of
      carcinoma cell lines expressed one or two of them. The tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) strongly
      enhanced the gene expression of the three subunits, increasing 2 to 8-fold the
      secretion of laminin-5 from carcinoma cells into culture medium. However, TPA
      treatment did not increase the secretion of laminin beta 1 chain, a subunit of
      laminins-1, -3, and -6. The unique properties and inducibility by TPA and EGF of
      laminin-5 suggest that it is associated with growth and migration of cancer
      cells.

PMID- 9010771
TI  - Inhibitory effect of a new butadiene derivative on the production of plasminogen
      activator inhibitor-1 in cultured bovine endothelial cells.
AB  - Tissue-type plasminogen activator (t-PA) and its physiological inhibitor,
      plasminogen activator inhibitor-1 (PAI-1), are known to be synthesized by
      vascular endothelial cells and to play important roles in regulating the
      fibrinolytic activity of plasma. We found that a new butadiene derivative, (3E,
      4E)-3-benzylidene-4-(3,4,5-trimethoxybenzylidene)pyrrolidine -2,5-dione (T-686),
      inhibits PAI-1 production without affecting plasminogen activator (PA) synthesis
      in cultured bovine endothelial cells. T-686 (1-10 microM) dose-dependently
      decreased the accumulation of PAI-1 in conditioned medium from the treated cells
      and elevated PA activity in the conditioned medium. Analysis of the conditioned
      medium by the zymography technique indicated that T-686 decreased the activities
      of PAI-1 with an M(r) of 55,000 and t-PA/PAI-1 complex with an M(r) of 99,000.
      Furthermore, T-686 attenuated the augmentation of PAI-1 antigen induced by
      lipopolysaccharide in the conditioned medium. The decrease of PAI-1 antigen was
      in parallel with the reduction of the PAI-1 mRNA level (Northern blots). These
      results suggest that T-686 can promote net fibrinolytic activity through
      suppression of PAI-1 production without affecting PA elaboration in endothelial
      cells.

PMID- 9010772
TI  - Exocytosis of arginine-specific ADP-ribosyltransferase and p33 induced by A23187
      and calcium or serum-opsonized zymosan in chicken polymorphonuclear leukocytes.
AB  - Exocytosis is a common phenomenon in neutrophil functions. We earlier reported
      the co-localization of arginine-specific ADP-ribosyltransferase [EC 2.4.2.31] and
      its target protein p33 (mim-1 protein) in cytoplasmic granules in chicken
      polymorphonuclear leukocytes (so-called heterophils) [Mishima, K., Terashima, M.,
      Obara, S., Yamada, K., Imai, K., and Shimoyama, M. (1991) J. Biochem. 110, 388
      394]. In the present study, we obtained evidence that the transferase and p33
      were released into the extracellular space by the stimulus of calcium ionophore
      A23187 or serum-opsonized zymosan, but scarcely by phorbol myristate acetate
      (PMA) or N-formyl-Met-Leu-Phe (fMLP), thereby indicating the co-localization of
      the transferase and p33 in the azurophilic granules, and not in specific
      granules. [32P]ADP-ribosylation of p33 occurred in the extracellular space,
      induced by the stimulus of A23187 or opsonized zymosan in the presence of
      [32P]NAD. Our findings are interpreted to mean that heterophil transferase and
      p33 may be involved in neutrophil functions during processes of inflammation.

PMID- 9010773
TI  - The structure, stability, and folding process of amyloidogenic mutant human
      lysozyme.
AB  - The physicochemical properties of an amyloidogenic mutant human lysozyme
      (Ile56Thr) were examined in order to elucidate the mechanism of amyloid
      formation. The crystal structure of the mutant protein was the same as the wild
      type structure, except that the hydroxyl group of the introduced Thr56 formed a
      hydrogen bond with a water molecule in the interior of the protein. The other
      physicochemical properties of the mutant protein in the native state were not
      different from those of the wild-type protein. However, the equilibrium and
      kinetic stabilities of the mutant protein were remarkably decreased due to the
      introduction of a polar residue (Thr) in the interior of the molecule. It can be
      concluded that the amyloid formation of the mutant human lysozyme is due to a
      tendency to favor (partly or/and completely) denatured structures.

PMID- 9010774
TI  - Conformational changes associated with activation of bee venom phospholipase A2.
AB  - Bee venom PLA2 possesses a binding site for long-chain fatty acids that can be
      acylated by long-chain fatty acid imidazolides [Drainas, D. and Lawrence, A.J.
      (1978) Eur. J. Biochem. 91, 131-138]. Occupation of the site either by oleic acid
      or the oleoyl residue enhances the catalytic activity by 45.7-fold in the
      presence of 20% 1-propanol and occupation of the site by the oleoyl residue
      increases the lytic activity against rabbit erythrocytes by 60-fold. Treatment of
      the enzyme with oleic acid and glutaraldehyde is known to produce irreversible
      activation [Lawrence, A.J. and Moores, G.R. (1975) FEBS Lett. 49, 287-291]. Here
      we show that reduction of the glutaraldehyde-treated enzyme with borohydride
      stabilizes the activated state and enables the fatty acid to be removed,
      revealing that a large proportion of the induced activation does not require the
      presence of oleic acid and indicating that activation is due to a change in the
      conformation rather than the hydrophobicity of the protein. A kinetic study of
      enzyme activated by oleoyl imidazolide showed that this modification stabilizes
      the protein against reversible inactivation by 1-propanol. Comparison of the CD
      spectra of native and oleoyl imidazolide-activated enzyme shows a change in
      secondary structure with apparent increase in both alpha-helix and beta-sheet
      content. During reaction of the enzyme with oleoyl imidazolide, the protein
      fluorescence shows a biphasic response with an initial fall attributed to
      occupation of the binding site followed by a progressive decrease with a shift of
      the emission maximum from 341 to 348 nm. The rate of the second phase closely
      matched the rate of increase in catalytic activity of the enzyme. Free oleic acid
      caused a rapid fall in fluorescence emission without the subsequent slow change.
      These results support the proposal that oleic acid or the oleoyl residue occupy a
      very similar site on the protein and that occupation of this site increases the
      exposure of one or both of the Trp residues to the aqueous environment. Binding
      studies show that activation by oleoyl imidazolide does not increase the affinity
      of the enzyme for the erythrocyte membrane. It is proposed that occupation of a
      long-chain fatty acid binding site on the enzyme enhances catalytic activity by
      changing the conformation of the protein rather than acting as a hydrophobic
      anchor to the substrate surface.

PMID- 9010775
TI  - Purification and functional reconstitution with GTP-binding regulatory proteins
      of hexahistidine-tagged muscarinic acetylcholine receptors (m2 subtype).
AB  - We have expressed human m2 muscarinic acetylcholine receptors tagged with six
      histidine residues at the carboxy-terminal region in insect cells (Sf9) and
      purified them using metal-immobilized Chelating Sepharose gels. Co(2+)
      immobilized gels were found to be much more efficient for purification of m2
      receptors than gels containing Ni2+ or other metal ions. Twenty-fold purification
      was attained by a simple, single-step procedure, and approximately 40% of
      solubilized receptors were recovered as a partially purified preparation with a
      specific activity of 1.6 nmol/mg of protein. Purified receptors were functionally
      active in that carbamylcholine stimulated binding of [35S]GTP gamma S to the G
      protein G12 reconstituted in lipid vesicles with purified m2 receptors. The
      extent of stimulation of [35S] GTP gamma S binding to G12 by hexahistidine-tagged
      m2 receptors was essentially the same as that observed for m2 receptors that lack
      histidine tags. In addition, palmitoylation at the carboxy-terminal region was
      not impaired by the hexahistidine-tag fusion. The method described in this study
      should be applicable to the purification of other G-protein-coupled receptors in
      functionally active form.

PMID- 9010776
TI  - Purification, characterization, and cDNA cloning of ABP-2 (arylphorin gene
      specific binding protein-2) that specifically binds to the ABP-1-binding sequence
      in the arylphorin gene of Sarcophaga peregrina.
AB  - Previously, we demonstrated that ABP-1 (arylphorin gene-specific binding protein
      1), which is suggested to be the transcriptional activator of the arylphorin gene
      of Sarcophaga peregrina, is present in NIH-Sape-4 cells, which do not express
      arylphorin. As well as ABP-1, these cells were found to contain another protein
      (ABP-2) that probably binds to the same sequence as that to which ABP-1 binds
      [Adachi, N., Kubo, T., and Natori, S. (1993) J. Biochem. 114, 55-60]. We purified
      ABP-2 from a nuclear extract of NIH-Sape-4 cells and compared its DNA-binding
      activity with that of ABP-1. Both ABP-1 and ABP-2 were found to bind to the same
      sequence in the arylphorin gene with the same affinity and stability, but an ABP
      2-specific hypersensitive site was detected by DNase I footprinting analysis.
      Analyses of proteolytic fragments suggested that both ABP-1 and ABP-2 have Zn
      fingers showing high similarity with that of AEF-1, a transcriptional repressor
      of the Drosophila melanogaster alcohol dehydrogenase gene that binds to a
      sequence very similar to that binding ABP-1 and ABP-2. We isolated a candidate
      cDNA for ABP-2, and the protein it encoded contained nine Zn fingers and regions
      rich in alanine, glutamine, serine/threonine, glycine, histidine, and asparagine.

PMID- 9010777
TI  - Requirement of calcium influx for hydrolytic action of membrane phospholipids by
      cytosolic phospholipase A2 rather than mitogen-activated protein kinase
      activation in Fc epsilon RI-stimulated rat peritoneal mast cells.
AB  - The mechanism by which cytosolic phospholipase A2 (cPLA2) is not responsible for
      eicosanoid production in rat peritoneal mast cells upon antigen stimulation
      [Ishimoto et al. (1996) J. Biochem. 120, 616-623] was investigated in the mast
      cells stimulated by cross-linking of the IgE receptor or with thapsigargin.
      Stimulation with thapsigargin, but not with antigen, resulted in apparent
      lysophosphatidylcholine (lysoPC) formation. Antigen stimulation significantly
      increased the activities of mitogen-activated protein (MAP) kinase and cPLA2.
      These activities were further potentiated by phorbol ester. The antigen elicited
      a rapid and transient increase in intracellular Ca2+ concentration, while
      thapsigargin produced a slow and sustained increase. Furthermore, a combination
      of antigen and thapsigargin rapidly increased and prolonged the intracellular
      Ca2+ concentration. Under these conditions, lysoPC was apparently generated,
      whereas it was not in response to antigen alone. These results suggest that a
      prolonged increase in the intracellular Ca2+ concentration is required for cPLA2
      to associate with membranes, thus leading to hydrolysis of membrane phospholipids
      by the enzyme.

PMID- 9010778
TI  - Tachycitin, a small granular component in horseshoe crab hemocytes, is an
      antimicrobial protein with chitin-binding activity.
AB  - Small granules of horseshoe crab hemocytes contain two known major antimicrobial
      substances, tachyplesin and big defensin (S5), and at least five protein
      components (S1 to S6), with unknown functions. In the present study, we examined
      the biological properties and primary structure of a small granular component S2,
      named tachycitin. This component was purified from the acid extract of hemocyte
      debris by two steps of chromatography. The purified tachycitin was a single chain
      protein with an apparent M(r) = 8,500 on Tricine-SDS-polyacrylamide gel
      electrophoresis. Ultracentrifugation analysis revealed tachycitin to be present
      in monomer form in solution. Tachycitin inhibited the growth of both Gram
      negative and -positive bacteria, and fungi, with a bacterial agglutinating
      property. Moreover, tachycitin and big defensin acted synergistically in
      antimicrobial activities. The amino acid sequence and intrachain disulfide bonds
      of tachycitin were determined by amino acid and sequence analyses of peptides
      produced by enzymatic cleavages. The mature tachycitin consisted of 73 amino acid
      residues containing five disulfide bonds with no N-linked sugar. A cDNA coding
      for tachycitin was isolated from a hemocyte cDNA library. The open reading frame
      coded for an NH2-terminal signal sequence followed by the mature peptide and an
      extension sequence of -Gly-Arg-Lys at the COOH-terminus, which is a putative
      amidating signal. The COOH-terminal threonine amide released after digestion of
      tachycitin with lysylendopeptidase was identified. The NH2-terminal 28 residues
      of tachycitin shows sequence homology to a part of chitin-binding regions found
      in antifungal chitin-binding peptides, chitin-binding lectins, and chitinases,
      all of which have been isolated from plants. Tachycitin showed a specific binding
      to chitin but did not bind with the polysaccharides cellulose, mannan, xylan, and
      laminarin. Tachycitin may represent a new class of chitin-binding protein family
      in animals.

PMID- 9010779
TI  - Embryoglycans regulate FGF-2-mediated mesoderm induction in the rabbit embryo.
AB  - Several peptide growth factors, including members of the fibroblast growth factor
      (FGF) superfamily, are potential inducers of mesoderm in vertebrates. Receptor
      binding of basic FGF (FGF-2) is promoted by cell surface or extracellular matrix
      proteoglycans. The substantial biosynthesis of proteoglycans by embryonic cells
      (called embryoglycans) and their potential role as ligands for growth factor
      receptors led us to examine the role of embryoglycans that carry the
      developmentally regulated oligosaccharide epitope TEC 1, in the binding of FGF-2
      to cultured rabbit inner cell masses (ICMs). Culture of isolated ICMs in the
      presence of FGF-2 gave rise to well delimited colonies with migrating cells at
      the periphery. In these cells, TEC 1 staining shifts from a punctate pattern over
      the entire membrane, to an apical, finely granular distribution with some
      internalization. This shift occurs after 96 hours in culture. Here we show that:
      (1) migrating cells are mesoderm-like in phenotype; (2) antibodies against TEC 1
      blocked FGF-2 mediated differentiation in vitro; (3) antibodies against TEC 1
      selectively blocked binding of FGF-2 to ectodermal receptors and, vice versa, the
      binding of TEC 1-specific antibodies to ectodermal cells can be competed by
      excess FGF-2; (4) the same switch in TEC 1 staining patterns was observed in
      vivo, between the day 7 and the day 9 rabbit embryo. These data suggest the
      involvement of defined species of embryonic cell surface epitopes in the
      regulation of FGF-2 receptor binding. Moreover, this proposed binding activity is
      temporally restricted to ectodermal cells and disappears early during
      differentiation. Thus, the apical TEC 1 redistribution can be considered as the
      earliest indicator of mesoderm formation.

PMID- 9010780
TI  - Calcium ions and tyrosine phosphorylation interact coordinately with actin to
      regulate cytoprotective responses to stretching.
AB  - The actin-dependent sensory and response elements of stromal cells that are
      involved in mechanical signal transduction are poorly understood. To study
      mechanotransduction we have described previously a collagen-magnetic bead model
      in which application of well-defined forces to integrins induces an immediate (<
      1 second) calcium influx. In this report we used the model to determine the role
      of calcium ions and tyrosine-phosphorylation in the regulation of force-mediated
      actin assembly and the resulting change in membrane rigidity. Collagen-beads were
      bound to cells through the focal adhesion-associated proteins talin, vinculin,
      alpha 2-integrin and beta-actin, indicating that force application was mediated
      through cytoskeletal elements. When force (2 N/m2) was applied to collagen beads,
      confocal microscopy showed a marked vertical extension of the cell which was
      counteracted by an actin-mediated retraction. Immunoblotting showed that force
      application induced F-actin accumulation at the bead-membrane complex but
      vinculin, talin and alpha 2-integrin remained unchanged. Atomic force microscopy
      showed that membrane rigidity increased 6-fold in the vicinity of beads which had
      been exposed to force. Force also induced tyrosine phosphorylation of several
      cytoplasmic proteins including paxillin. The force-induced actin accumulation was
      blocked in cells loaded with BAPTA/AM or in cells preincubated with genistein, an
      inhibitor of tyrosine phosphorylation. Repeated force application progressively
      inhibited the amplitude of force-induced calcium ion flux. As force-induced actin
      reorganization was dependent on calcium and tyrosine phosphorylation, and as
      progressive increases of filamentous actin in the submembrane cortex were
      correlated with increased membrane rigidity and dampened calcium influx, we
      suggest that cortical actin regulates stretch-activated cation permeable channel
      activity and provides a desensitization mechanism for cells exposed to repeated
      long-term mechanical stimuli. The actin response may be cytoprotective since it
      counteracts the initial force-mediated membrane extension and potentially
      strengthens cytoskeletal integrity at force-transfer points.

PMID- 9010782
TI  - Subpellicular microtubules associate with an intramembranous particle lattice in
      the protozoan parasite Toxoplasma gondii.
AB  - Application of Fourier analysis techniques to images of isolated, frozen-hydrated
      subpellicular microtubules from the protozoan parasite Toxoplasma gondii
      demonstrates a distinctive 32 nm periodicity along the length of the
      microtubules. A 32 nm longitudinal repeat is also observed in the double rows of
      intramembranous particles seen in freeze-fracture images of the parasite's
      pellicle; these rows are thought to overlie the subpellicular microtubules.
      Remarkably, the 32 nm intramembranous particle periodicity is carried over
      laterally to the single rows of particles that lie between the microtubule
      associated double rows. This creates a two-dimensional particle lattice, with the
      second dimension at an angle of approximately 75 degrees to the longitudinal rows
      (depending on position along the length of the parasite). Drugs that disrupt
      known cytoskeletal components fail to destroy the integrity of the particle
      lattice. This intramembranous particle organization suggests the existence of
      multiple cytoskeletal filaments of unknown identity. Filaments associated with
      the particle lattice provide a possible mechanism for motility and shape change
      in Toxoplasma: distortion of the lattice may mediate the twirling motility seen
      upon host-cell lysis, and morphological changes observed during invasion.

PMID- 9010781
TI  - Protein phosphatases maintain the organization and structural interactions of
      hepatic keratin intermediate filaments.
AB  - The importance of protein phosphatases in the maintenance of cytoskeletal
      structure is supported by the serious liver injury caused by microcystin-LR, a
      hepatotoxic inhibitor of type-1 and type-2A serine/threonine protein
      phosphatases. We used the microcystin-LR-induced cell injury as a model to study
      the roles of protein dephosphorylation in maintaining cytoskeletal structure and
      cellular interactions in primary rat hepatocyte cultures. Confocal microscopy
      revealed that the first visible effect of microcystin-LR is disruption of
      desmoplakin organization at the cell surface, indicating dissociation of
      desmosomes. This effect is followed by a dramatic reorganization of both the
      intermediate filament (keratins 8 and 18) and microfilament networks, resulting
      in a merged structure in which the intermediate filaments are organized around a
      condensed actin core. Keratin 8, keratin 18 and desmoplakin I/II are the major
      cytoskeleton-associated targets for microcystin-LR-induced phosphorylation.
      Hyperphosphorylation of keratin 8 and 18 is accompanied by an increased keratin
      solubility, which correlates with the observed morphological effects.
      Phosphopeptide mapping shows that four specific tryptic phosphopeptides are
      highly phosphorylated predominantly in the soluble pool of keratin 18, whereas
      keratin 8 shows no indications of such assembly state-specific sites.
      Phosphopeptide maps of keratins phosphorylated in vivo and in vitro indicate that
      Ca2+/calmodulin-dependent kinase may be involved in regulating the serine
      specific phosphorylation of both keratin 8 and keratin 18, while cAMP-dependent
      protein kinase does not seem to play a major role in this context. Taken
      together, our results show that the interactions between keratin intermediate
      filaments and desmosomes as well as the assembly states of their main constituent
      proteins, are directly regulated by serine/threonine kinase/phosphatase
      equilibria.

PMID- 9010783
TI  - Prenucleolar bodies contain coilin and are assembled in Xenopus egg extract
      depleted of specific nucleolar proteins and U3 RNA.
AB  - Nuclei assembled in Xenopus egg extract contain numerous spherical aggregations
      or nuclear bodies. Previously we have shown that they closely resemble
      prenucleolar bodies (PNBs), both at the compositional and ultrastructural level.
      Subsequently, coilin was also identified and for this reason they were called
      coiled bodies. Here we present morphological and immunocytochemical evidence that
      the in vitro nuclear bodies resemble authentic PNBs and are different from coiled
      bodies. In particular we show that coilin, previously considered as the defining
      protein constituent of coiled bodies, is also present in PNBs of cultured cells.
      In contrast, the PNB-associated nucleolar proteins nucleolin and B23/NO38 are not
      detectable in coiled bodies and may thus serve as suitable markers for PNBs. Our
      results suggest that PNBs are primary assembly structures which contribute to the
      formation of both nucleoli and coiled bodies and thus offer an explanation for
      the frequently observed structural association of coiled bodies with nucleoli. To
      gain some insight into the assembly process of PNBs in vitro, specific nucleolar
      proteins were removed from Xenopus egg extract. Quite surprisingly, the immuno
      depleted extracts still promoted the assembly of nuclear bodies which lacked
      either fibrillarin, nucleolin, xNopp180 or B23/NO38. Only after fibrillarin
      depletion fewer PNBs were seen as compared to controls. Digestion of the extract
      with RNase followed by northern blot analysis revealed that U3 small nucleolar
      RNA is not required for the formation and structural maintenance of PNBs in
      vitro.

PMID- 9010784
TI  - The role of laminin-5 and its receptors in mammary epithelial cell branching
      morphogenesis.
AB  - In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices
      to adhere to stroma. However, analyses of a potential role for hemidesmosomes and
      their components in mammary epithelial tissue morphogenesis have never been
      attempted. MCF-10A cells are a spontaneously immortalized line derived from
      mammary epithelium and possess a number of characteristics of normal mammary
      epithelial cells including expression of hemidesmosomal associated proteins such
      as the two bullous pemphigoid antigens, alpha 6 beta 4 integrin and its ligand
      laminin-5. More importantly, MCF-10A cells readily assemble mature hemidesmosomes
      when plated onto uncoated substrates. When maintained on matrigel, like their
      normal breast epithelial cell counterparts, MCF-10A cells undergo a branching
      morphogenesis and assemble hemidesmosomes at sites of cell-matrigel interaction.
      Function blocking antibodies specific for human laminin-5 and the alpha subunits
      of its two known receptors (alpha 3 beta 1 and alpha 6 beta 4 integrin) not only
      inhibit hemidesmosome assembly by MCF-10A cells but also impede branching
      morphogenesis induced by matrigel. Our results imply that the hemidesmosome, in
      particular those subunits comprising its laminin-5/integrin 'backbone', play an
      important role in morphogenetic events. We discuss these results in light of
      recent evidence that hemidesmosomes are sites involved in signal transduction.

PMID- 9010785
TI  - ERD2 proteins mediate ER retention of the HNEL signal of LRP's receptor
      associated protein (RAP).
AB  - The 39 kDa receptor-associated protein (RAP) is a receptor antagonist that
      interacts with several members of the low density lipoprotein (LDL) receptor gene
      family. Upon binding to these receptors, RAP inhibits all ligand interactions
      with the receptors. Our recent studies have demonstrated that RAP is an
      endoplasmic reticulum (ER) resident protein and an intracellular chaperone for
      the LDL receptor-related protein (LRP). The HNEL sequence at the carboxyl
      terminus of RAP represents a novel ER retention signal that shares homology with
      the well-characterized KDEL signal. In the present study, using immunoelectron
      microscopy we demonstrate that cells stably transfected with human growth hormone
      (GH) tagged with either KDEL (GH + KDEL) or HNEL (GH + HNEL) signals exhibit ER
      and cis-Golgi localization typical of ER-retained proteins. Overexpression of not
      only GH + HNEL but also GH + KDEL cDNA in transfected cells results in saturation
      of ER retention receptors and secretion of endogenous RAP indicating that the two
      signals interact with the same ER retention receptor(s). The role of RAP in the
      maturation of LRP is further supported by the observation that functional LRP is
      reduced about 60% as a result of decreased intracellular RAP. Pulse-chase
      labeling and immunolocalization studies of ERD2.1 and ERD2.2 proteins in
      transfected cells demonstrate a long half-life and Golgi localization for both
      receptors. Finally, overexpression of either ERD2.1 or ERD2.2 proteins
      significantly increases the capacity of cells to retain both KDEL and HNEL
      containing proteins. Taken together, our results thus demonstrate that ERD2
      proteins are capable of retaining the novel ER retention signal associated with
      RAP.

PMID- 9010786
TI  - Transport of sphingomyelin to the cell surface is inhibited by brefeldin A and in
      mitosis, where C6-NBD-sphingomyelin is translocated across the plasma membrane by
      a multidrug transporter activity.
AB  - Sphingomyelin is a major lipid of the mammalian cell surface. The view that
      sphingomyelin, after synthesis in the Golgi lumen, reaches the outer leaflet of
      the plasma membrane on the inside of carrier vesicles has been challenged by
      inconsistencies in the results of transport studies. To investigate whether an
      alternative pathway to the cell surface exists for sphingomyelin, brefeldin A and
      mitotic cells were used to block vesicular traffic between the Golgi complex and
      the plasma membrane. Exogenous sphingomyelinase was applied in the cold to assay
      for the presence of sphingomyelin on the surface of CHO cells. Newly synthesized
      radiolabeled sphingomyelin was found to equilibrate with cell surface
      sphingomyelin within 1.5 hours at 37 degrees C. Brefeldin A and mitosis inhibited
      this transport but, surprisingly, not the surface appearance of the short-chain
      sphingomyelin analog N-6[7-nitro-2,1,3-benzoxadiazol-4-yl]aminohexanoyl(C6-NBD)
      sphingo myelin as assayed by depletion of this lipid in the medium by the
      scavenger albumin. Transport of C6-NBD-sphingomyelin in the presence of brefeldin
      A was blocked by cyclosporin A and PSC 833, inhibitors of the multidrug
      resistance P-glycoprotein. The same was observed in HepG2 and HeLa cells, and for
      short-chain glucosylceramide, which demonstrates the general nature of the
      transporter-dependent sphingolipid translocation across the plasma membrane.

PMID- 9010787
TI  - Studies on the eel sperm flagellum. I. The structure of the inner dynein arm
      complex.
AB  - The highly motile, 9 + 0 sperm axoneme of Anguilla has inner dynein arms (IDAs)
      but not outer dynein arms. The in situ morphology of these IDAs is shown here to
      be essentially identical to the IDA morphology already seen in the axonemes of
      Chlamydomonas, Tetrahymena and Beroe, and in the sperm tails of echinoderms and
      several vertebrate species. In addition, this study demonstrates: (1) that the
      nexin (circumferential) links are present in Anguilla and are typical; (2) that
      IDA1 incorporates an archway, supported by a pillar-structure; (3) that images
      from thin sections and whole mounts are consistent with those from replicas of
      rapidly-frozen specimens; and (4) that the IDA and nexin link morphology is
      apparently unaffected by whether the axoneme is depleted of ATP, relaxed with ATP
      and vanadate, or inhibited by high ATP. An attempt has been made to reconcile the
      emergent morphology of the IDA complex with all earlier descriptions in the
      literature. From a detailed comparison of the results with published information
      on Chlamydomanas mutants, it is concluded that the nexin (circumferential) link
      is a major part of the 'dynein regulatory complex'.

PMID- 9010788
TI  - SFV infection in CHO cells: cell-type specific restrictions to productive virus
      entry at the cell surface.
AB  - Alphaviruses, such as Semliki Forest virus, normally enter cells by penetration
      from acidic organelles of the endocytic pathway. The virions are internalised
      intact from the cell surface before undergoing acid-induced fusion in endosomes.
      To investigate the possibility that endocytosis might play a role in delivering
      virions to specific sites for replication, we compared SFV infection of baby
      hamster kidney (BHK) cells and Chinese hamster ovary (CHO) cells following either
      normal virus fusion in endosomes or experimentally-induced fusion at the cell
      surface. Whereas baby hamster kidney cells were infected efficiently following
      fusion in endosomes or at the plasma membrane, Chinese hamster ovary cells were
      only infected following fusion from endocytic organelles. Virions fused at the
      plasma membrane of CHO cells failed to initiate viral RNA and protein synthesis.
      Similar results were observed when CHO cells were challenged with a rhabdovirus,
      vesicular stomatitis virus. These data suggest that in certain cell types a
      barrier, other than the plasma membrane, can prevent infection by alpha- and
      rhabdoviruses fused at the cell surface. Moreover, they suggest the endocytic
      pathway provides a mechanism for bringing viral particles to a site, or sites, in
      the cell where replication can proceed.

PMID- 9010789
TI  - Gene therapy for neurologic disease: benchtop discoveries to bedside
      applications. 1. The bench.
AB  - The overall goal of this review is to provide the pediatric neurologist with a
      theoretical foundation in gene therapy. Gene therapy became feasible in the early
      1970s and the first transfer of a foreign gene into humans was approved by the
      NIH in 1989. Adenovirus, adeno-associated virus, herpes-simplex virus,
      retroviruses, and other vectors have been used to efficiently transduce genes
      into cells in vitro and in vivo. We discuss laboratory experiments that have
      provided a strong scientific rationale for implementing human clinical trials of
      gene therapy for neurologic malignancy. The development of viral and nonviral
      vectors that mediate efficient gene insertion into human cells has created the
      prospect of using gene therapy for cancer or brain disease. The NIH has approved
      more than 100 gene therapy protocols since 1989. However, the field will require
      more research on gene delivery systems before gene therapy becomes an established
      therapeutic strategy for an array of central nervous system diseases.

PMID- 9010790
TI  - Study of nerve conduction and late responses in normal Chinese infants, children,
      and adults.
AB  - Healthy Chinese individuals (n = 168), aged from 24 hours to 30 years, were
      studied to establish the following normal values: (1) motor conduction velocity,
      distal latency, amplitude, and F-wave velocity in the median, ulnar, tibial, and
      peroneal nerves; (2) H-reflex velocity and latency in the tibial nerve for all
      subjects as well as in the median and ulnar nerves in infants; (3) sensory
      conduction velocity, latency, and amplitude in the median, ulnar, and sural
      nerves; and (4) the difference in minimal latencies of both H-reflex and F-waves
      between corresponding nerves in opposite limbs and between two nerves in the same
      limb. The motor conduction velocities, sensory conduction velocities, F-wave
      velocities, and H-reflex velocities in newborns were approximately 50%, 40%, 40
      to 45%, and 40 to 45% of adult values, respectively. At age 3 years, the normal
      values were in the adult range for all motor conduction velocities and for the
      sensory conduction velocities in the upper limbs. The sensory conduction
      velocities, H-reflex velocities, and F-wave velocities in the lower limbs did not
      reach adult values until age 6 years whereas the upper limb F-wave velocities
      reached adult levels between 6 and 14 years in different nerves. These results
      indicate that adult values for nerve conduction velocities, including the late
      responses, are reached earlier in the lower extremities; however, conduction
      velocities at any age are always faster in the upper limbs and in the proximal
      compared to the distal segments. The maturation process occurs most rapidly
      during the first 3 to 6 years of life, especially in the first year. This
      parallels the histologic development of peripheral nerves during childhood.

PMID- 9010791
TI  - Protein C and protein S activity in sickle cell disease and stroke.
AB  - Stroke is a significant complication of sickle cell anemia in the pediatric
      population. The pathophysiology of stroke in sickle cell anemia remains unclear.
      Protein C and protein S activities were measured in children with sickle cell
      anemia and stroke, and compared to those with sickle cell anemia who were
      neurologically normal. Results showed significantly decreased levels of both
      protein C and protein S activities in children with sickle cell anemia who have
      had a stroke. This pilot study suggests that a possible coagulopathic state in
      children with sickle cell anemia may be associated with an increased risk for
      cerebrovascular disease. Further research in this area is indicated.

PMID- 9010792
TI  - Infantile intranuclear rod myopathy.
AB  - This report concerns three unrelated floppy infants, two girls and one boy, each
      biopsied at the age of 1 month. They were hypotonic since birth and required
      artificial ventilation. The two girls died at the ages of 4 and 3 1/2 months,
      respectively, the boy is still alive at the age of 2 years, but requires assisted
      ventilation. Each of the three infants showed, by muscle biopsy, abundant
      intranuclear rods, the boy and one girl also had sarcoplasmic rods, which were
      not present in the other girl's muscle. Absence of sarcoplasmic rods, but the
      presence of intranuclear rods could also be documented in her autopsied muscle.
      Using an antibody against alpha-actinin, immunoelectron microscopy showed
      reaction of the sarcoplasmic and intranuclear rods demonstrating their Z-band
      origin. To our knowledge, this is the first report on rod myopathy with
      intranuclear rods only and of an immunoelectron microscopic demonstration of
      alpha-actinin in intranuclear rods. The presence of intranuclear rods in infants
      with nemaline myopathy also appears to indicate a grave prognosis of their rod
      myopathy.

PMID- 9010793
TI  - D-2-hydroxyglutaric aciduria: hypotonia, cortical blindness, seizures,
      cardiomyopathy, and cylindrical spirals in skeletal muscle.
AB  - An infant girl was demonstrated to have D-2-hydroxyglutaric aciduria, the fifth
      case described and the first with muscle biopsy of this rare organic aciduria
      that differs clinically and genetically from the more common L-2-hydroxyglutaric
      aciduria. Her clinical features included mildly dysmorphic facies, developmental
      delay, generalized hypotonia, myoclonic seizures, cortical blindness, and dilated
      cardiomyopathy requiring treatment. Muscle biopsy demonstrated only excessive
      glycogen histochemically, but ultrastructural examination revealed subsarcolemmal
      cylindrical spirals and normal mitochondria. Because of the metabolism of D-2
      hydroxyglutaric aciduria, we regard valproic acid as contraindicated in the
      treatment of epilepsy in this disease.

PMID- 9010794
TI  - An instrument to measure independent walking: are there differences between
      preterm and fullterm infants?
AB  - In clinical practice walking independently has always been considered a major
      milestone in development. Nevertheless, little attention has been paid to the
      quality of movement expressed in the first attempts at walking free. Even when
      children achieve walking within a normal time range, some of them show features
      that are deviant. Early walking is difficult to judge, but at the same time may
      provide a sensitive means for detecting possible developmental impairments. The
      main aim of this paper is to provide a standardized clinical instrument for the
      qualitative assessment of early walking in a structured free field situation and
      to compare preterm and fullterm infants. All subjects were assessed 14 days after
      being able to walk 5 meters independently. The study group consisted of 52
      children, of whom 33 were born prematurely (further distinguished in terms of
      being small- or appropriate-for-gestational age), and 19 were born fullterm.
      Judgments of walking performance were made in terms of optimal, near-optimal,
      near-poor, or poor. After correction for age, the preterm group was still later
      in the onset of walking, but more importantly, showed a qualitatively different
      pattern of locomotion. Those who were the youngest and small-for-gestational age
      were overrepresented in the near-poor and poor categories of walking.

PMID- 9010795
TI  - Clinical role of positron emission tomography in children with tuberous sclerosis
      complex.
AB  - We evaluated the clinical role of positron emission tomography (PET) in 23
      children with tuberous sclerosis complex. Mean age of the children when first
      scanned was 3.3 years. Mean age when seizures began was 8.7 months. All, except
      three, were at least mildly developmentally delayed. PET images were visually
      analyzed and compared to computed tomography (CT), magnetic resonance imaging
      (MRI), and the electroencephalogram (EEG). In two infants, interictal PET study
      was normal. One of the studies was performed with a low resolution early
      generation scanner at age 7 months; the other infant was 2 days old. Twenty-one
      of the 23 children had focal or multifocal cortical hypometabolism. Some
      hypometabolic cortical regions on PET did not show corresponding abnormalities on
      CT and MRI, and may be due to epileptogenic mechanisms or small tubers. PET
      provides additional localizing information to CT and MRI in patients with
      tuberous sclerosis complex. However, because of the normally low cerebral glucose
      metabolism in infancy, PET may give false negative findings if performed prior to
      about 1 year of age. The usefulness of glucose metabolism PET in most patients
      with tuberous sclerosis complex is limited. However, if the EEG, CT, and MRI
      abnormalities are unifocal or unilateral, and surgery is being contemplated, more
      detailed evaluation with PET may help to determine if contralateral tubers are
      present and evaluate the functional integrity of the brain as a whole.

PMID- 9010796
TI  - Pediatric leptomeningeal metastases: outcome following combined therapy.
AB  - Fifteen children ranging in age from 4 to 18 years with leptomeningeal metastases
      were evaluated for extent of tumor and treated with radiotherapy or chemotherapy.
      Histologic diagnosis included: acute lymphoblastic leukemia (4); anaplastic
      astrocytoma (1); ependymoma (2); nonseminomatous germ cell tumor (1); non
      Hodgkin's lymphoma (1); pineoblastoma (1); and primitive neuroectodermal tumor
      not otherwise specified (2). Pretreatment imaging studies demonstrated recurrent
      intracranial parenchymal disease in nine, spinal disease in four, and abnormal
      radioisotope ventriculography in six. Systemic disease was seen in four children
      (3 leukemia; 1 non-Hodgkin's lymphoma). All children were treated with systemic
      chemotherapy and intraventricular chemotherapy. Nine children received
      radiotherapy to bulky or symptomatic leptomeningeal disease. Median survival was
      6 months (range, 4-18 months). Children with hematologic malignancies had
      superior outcomes compared to children with solid tumors. Three children with
      leukemic or lymphomatous meningitis are alive and disease free whereas all
      children with carcinomatous meningitis died. In conclusion, leptomeningeal
      metastases in children portends a limited survival, and therapies at this time
      remain palliative except in children with hematologic malignancies.

PMID- 9010797
TI  - Expression of HLA class I antigens in skeletal muscle is a diagnostic marker in
      juvenile dermatomyositis.
AB  - HLA class I gene products are immunocytochemically detectable in the skeletal
      muscle of many patients with inflammatory conditions. We report three cases of
      juvenile dermatomyositis with minimal histologic abnormalities and no
      inflammation in the muscle biopsies. All three showed strong expression of HLA
      class I antigens on muscle fibers. Analysis of HLA class I expression is thus a
      useful marker for the diagnosis of inflammatory muscle disease, even in the
      absence of histologic changes.

PMID- 9010798
TI  - Treatment with high doses of lamotrigine in children and adolescents with
      refractory seizures.

PMID- 9010799
TI  - Two cases of dysembryoplastic neuroepithelial tumors with intractable complex
      partial seizures.

PMID- 9010800
TI  - Central nervous system involvement in X-linked myotubular myopathy.

PMID- 9010801
TI  - Abdominal ultrasound findings of disseminated tuberculosis in AIDS.
AB  - The sonographic findings of 76 patients with tuberculosis and HIV infection are
      described. These findings were compared with a control group of 76 HIV-positive
      patients without associated pathology. Those patients with tuberculosis and
      positive HIV titers commonly (p = 0.05) showed retroperitoneal and mesenteric
      adenopathies with node diameters greater than 1.5 cm (n = 27), and multiple,
      splenic, hypoechoic nodules between 0.5 cm and 1 cm (n = 11). Additional findings
      include hepatic hyperechoic nodules (n = 1) and retroperitoneal abscess (n = 1).
      The combination of ultrasound features can help in the diagnosis of abdominal
      tuberculosis in HIV-positive patients with non-specific clinical infections.

PMID- 9010802
TI  - Changes in diameter of the abdominal aorta with age: an epidemiological study.
AB  - Rupture of abdominal aortic aneurysms is a major cause of death for men who are
      over 60 years old. This study invited 13,000 men aged 60 to 75 years, within the
      Birmingham conurbation, to have an ultrasound scan of the abdominal aorta. The
      scan was performed at the patients' own General Practitioner's surgery; 10,061
      men were scanned. Only 3% of this population were found to have large aneurysms.
      An analysis of the distribution of aortic diameters in this population shows that
      for diameters less than 40 mm, changes in the diameter with age (previously
      attributed to the growth of small aneurysms) occurs for up to 25% of the
      population although the median diameter for each year group, 21 mm, does not
      increase with age. This analysis suggests that the threshold diameter at which
      the aorta is categorized as abnormal should be related to age, especially by
      those undertaking mass screening.

PMID- 9010803
TI  - Hepatic vein Doppler waveform changes in early stage (Child-Pugh A) chronic
      parenchymal liver disease.
AB  - Doppler waveform changes can be found in chronic parenchymal liver disease,
      especially in the late stages. We investigated the contribution of Doppler
      ultrasound in diagnosing early-stage chronic parenchymal liver disease. In this
      prospective study, 30 patients who had been diagnosed with chronic liver disease
      (Child-Pugh class A) and 30 healthy subjects were studied. The diagnosis was
      confirmed with histopathologic examinations of biopsy specimens in 17 patients.
      The Doppler US examination of hepatic veins was performed in all the patients and
      healthy subjects. The Doppler US pattern was classified into three groups
      according to the Doppler signal characteristics: (1) type 0, triphasic waveform,
      the presence of a short phase of reversed flow, (2) type I, decreased amplitude
      of the phasic oscillations without the short phase of reversed flow, and (3) type
      II, complete flat waveform. Normal hepatic vein waveforms (type 0) were found in
      8 patients (26.66%) and abnormal hepatic waveforms (type I + type II) in 22
      patients (73.33%). The results of Doppler ultrasonography were correlated with
      the diagnosis of early-stage chronic parenchymal liver disease (Child-Pugh class
      A). In all the subjects of the control group, the Doppler waveform of hepatic
      veins showed the triphasic pattern (type 0). In the statistical evaluation using
      Fisher's exact test we observed that there was a significant difference (p <
      0.05) between the control group and the patient group with respect to the
      presence of abnormal (type I + type II) Doppler waveform. The diagnostic accuracy
      in the patients who had biopsy was 76.47% and that in the patients who did not
      was 69.23%.

PMID- 9010804
TI  - Transrectal ultrasonography in the diagnosis of urethral diverticula in women.
AB  - The diagnosis of urethral diverticula in women can be difficult. Several imaging
      modalities have been described for evaluating this entity: urethrography;
      transabdominal, transrectal, transvaginal, and transperineal ultrasonography;
      computed tomography (CT); and magnetic resonance (MR) can be helpful in
      evaluating a diverticulum and its relationship to the urethra. We report on four
      women aged 36 to 42 years with urethral diverticula. Transrectal ultrasonography
      (TRU) was the most useful diagnostic test in our series. TRU showed 7 urethral
      diverticula and provided information about its shape, volume, and content as well
      as its spatial relationship about its shape, volume, and content as well as its
      spatial relationship to the urethra. In two cases, multiple diverticula were
      detected when only a single lesion was clinically suspected. Transabdominal
      sonography failed to demonstrate small diverticula. CT examination did not
      provide additional information except for the passage of the contrast from the
      urethra to the diverticulum in one of the cases. Voiding cystourethrogram was
      positive in only one patient.

PMID- 9010805
TI  - Image-directed color Doppler ultrasound evaluation of the single kidney after
      unilateral nephrectomy in adults.
AB  - Renal adaptations occur in the single kidney. The kidney of 21 unilaterally
      nephrectomized adults was studied with image-directed color Doppler ultrasound
      (ICDU) and compared with 35 age-matched controls. Kidney volume, standardized
      kidney volume, hypertrophy, both intrarenal- and main renal artery-resistive
      indexes were quantified, correlated to each other and correlated to renal
      function. The influence of age, sex, or time since nephrectomy was also studied.
      There was a mean hypertrophy of approximately 20%. Intrarenal resistances lay
      within normal limits for age. There was no correlation between renal function,
      size, and hemodynamics. Age, sex, and time since nephrectomy had a limited
      influence on renal adaptations.

PMID- 9010806
TI  - Ultrasonographic diagnosis of first trimester hydatidiform mole.

PMID- 9010807
TI  - Rapid growth of a fetal abdominal mass: a case report of congenital
      neuroblastoma.

PMID- 9010808
TI  - Idiopathic hydrocele and absent testicular diastolic flow.

PMID- 9010809
TI  - Bartholin gland abscess: sonographic findings.

PMID- 9010810
TI  - Sonographic detection of lipomyelomeningocele: a retrospective documentation.

PMID- 9010811
TI  - Targeting technologies--recent patent literature.
AB  - The patent literature is rich with information about ideas and approaches related
      to targeted drug delivery. Although there is a typically a delay in the release
      of this information compared to that published in journal articles, some of the
      subject matter of patent applications is never released through any other medium
      and the breadth of anticipated uses is described best in the patent literature.
      As with any form of information, the patent literature can only provide an
      historical perspective of what has already occurred. However, the trends of this
      literature clearly points to the possibilities for the future in drug targeting.

PMID- 9010812
TI  - Oral protein drug delivery.

PMID- 9010813
TI  - Distribution of DNA and alginate in purulent cystic fibrosis sputum: implications
      to pulmonary targeting strategies.
AB  - Cystic fibrosis (CF) patients frequently experience recurring airway infections
      characterized by thick, viscous sputum. The consistency and nature of these
      purulent secretions may produce a significant barrier to the successful delivery
      of drugs and gene therapy vectors designed to treat CF. We have carried out a
      series of in vitro studies to determine the distribution of two macromolecular
      components typically present in purulent sputum, bacterial alginate and
      neutrophil-derived DNA. Sputum samples were obtained from hospitalized CF
      patients. DNA and alginate were disrupted, respectively, by the in vitro
      additions of human recombinant deoxyribonuclease I (rhDNase) or alginate lyase
      prepared from a mucoid strain of Pseudomonas aeruginosa. N-acetyl-L-cysteine
      (acetylcysteine) was similarly used to collapse the mucin matrix of these samples
      for comparison. Using a centrifugation-based rheological method known as the
      compaction assay, a greater maximal response was observed for rhDNase compared to
      alginate lyase treatment. A simultaneous addition of these enzymes to purulent
      sputum produced an additive compaction response. Electron microscopy was used to
      identify alginate and DNA components within the mucin matrix of sputa and to
      evaluate changes following treatment with high concentrations of alginate lyase
      or rhDNase. DNA was more widely distributed throughout purulent samples than
      alginate. Differences in the distribution of DNA and alginate may explain, at
      least in part, the larger compaction response to rhDNase versus alginate lyase
      treatment. An improved understanding of DNA and alginate distribution within
      purulent CF sputum may lead to improvements in drug and vector delivery to airway
      epithelial cells.

PMID- 9010814
TI  - Evaluation of dipalmitoylphosphatidylcholine liposomes containing a soybean
      derived sterylglucoside mixture for liver targeting.
AB  - We investigated multilamellar vesicle (MLV) liposomes composed of
      dipalmitoylphosphatidylcholine (DPPC) and a soybean-derived sterylglucoside
      mixture (SG) (DPPC/SG-liposomes) for targeting liver parenchymal cells after
      administration via the tail vein in mice, using liposome-entrapping calcein. The
      accumulation of DPPC/SG(7:2, mole ratio, DPPC:SG = 7:2)-liposomes in the liver
      was the highest among DPPC/SG-liposomes. About 80% and 40% of the dose of
      DPPC/SG(7:2)-liposomes accumulated in the liver at 15 min and 2 h, respectively,
      but about 20% of DPPC/SG(7:3.5, 7:7)-liposomes accumulated at 2 h after an
      intravenous administration. However, the uptake of DPPC/SG(7:2, 7:3.5, 7:7)
      liposomes by liver parenchymal cells was about 7 times greater than that in non
      parenchymal cells irrespective of the SG concentration in liposomes. The uptake
      of DPPC/SG(7:2)-liposomes in liver was almost the same level as that by liposomes
      containing lactocylceramide (LC) (LC-liposomes) that were already known to be
      taken up in liver parenchymal cells by the asialoglycoprotein receptor.
      DPPC/SG(7:2)-liposomes effectively targeted liver, having optimal stability and
      SG.

PMID- 9010815
TI  - Effects of intraperitoneal administration of free and liposome-entrapped
      doxorubicin on rat peritoneal exudate cell populations.
AB  - In the present paper effects of i.p. treatment with free or liposome-entrapped
      doxorubicin (DXR) on rat peritoneal exudate cell (PEC) populations were examined.
      Two types of DXR-liposomes were used: one type consisting of egg
      phosphatidylcholine/phosphatidylserine/cholesterol (molar ratio 10/1/4, mean size
      approx. 0.3 micron) and the other type of
      distearoylphosphatidylcholine/dipalmitoylglycerol/cholesterol (molar ratio
      10/1/10, mean size approx. 0.8 micron). Dramatically fewer PEC could be recovered
      from rats given free DXR or DXR-liposomes i.p. (10 mg DXR/kg body weight) 24 h
      before sacrifice than from control rats. Also the ratio of leukocyte species was
      modified by treatment with DXR, in free or liposomal form; in both cases the
      relative number of macrophages tended to increase. HPLC determination of the
      amount of DXR associated with monolayers obtained by seeding PEC harvested after
      a single i.p. dose of free DXR or liposomal DXR suggests that peritoneal
      macrophages are not particularly active in endocytosing DXR-liposomes. It was
      observed that the peritoneal macrophages phagocytosed DXR-containing granules
      from degranulating mast cells after both i.p. treatment with free DXR and DXR
      liposomes. Decreased yields of PEC following i.p. treatment with free or
      liposomal DXR as well as an involvement of mast cells in the processing of both
      free DXR and liposome-encapsulated DXR in the peritoneal cavity may have
      important consequences for approaches to i.p. chemotherapy.

PMID- 9010816
TI  - Good communication between hospitals, the practitioners outside, and patients.

PMID- 9010817
TI  - Report on the introduction of clinical indicators in surgery.

PMID- 9010818
TI  - A survey of general practitioners: implications for the hospital/community
      interface.
AB  - This paper presents the results of a survey that was conducted under the auspices
      of a Commonwealth-funded Ambulatory Care Reform Project. The survey was
      undertaken in all telephone areas of South Australia (08, 085, 086, 087, 088) to
      investigate issues of access to, and availability of, clinical allied health
      outpatient services at the Royal Adelaide Hospital with respect to general
      practitioners. Six hundred and twenty general practitioners in South Australia
      received a mailed survey enclosing a reply-paid envelop. Forty-nine per cent of
      the general practitioners responded. The highest response was from practitioners
      in the metropolitan area (08 telephone area) and the immediate Adelaide country
      area (085 telephone area). General practitioners supplied quality and in-depth
      responses that clearly indicated issues they felt impeded full use of clinical
      allied health services at the Royal Adelaide Hospital. These issues have
      implications not only for the clinical allied health outpatient services at the
      Royal Adelaide Hospital, but for all clinical allied health outpatient services
      in the public hospital system.

PMID- 9010819
TI  - General practitioner perceptions of surgical waiting times.
AB  - This study explored general practitioners' (GP) perceptions of waiting times and
      the importance of these perceptions in choosing a surgeon. A randomly selected
      sample of GPs in the Hunter Area of New South Wales, Australia, provided
      information prospectively on patients referred to a surgeon. The results
      indicated that GPs feel a lack of private health insurance makes only a small
      difference in waiting time to see a surgeon but a large difference in the waiting
      time for an operation. Additionally, GPs consider that sizeable numbers of
      patients will wait longer than they consider reasonable for surgical
      consultations and procedures. However, perceptions of waiting times do not appear
      to have a major influence on the choice of surgeon.

PMID- 9010820
TI  - A methodology for measuring clinical outcomes in an acute care teaching hospital.
AB  - The purpose of this study was to assess risk-adjusted outcomes following renal
      failure, gastrointestinal haemorrhage, stroke, myocardial infarction and heart
      failure. Length of stay, death and unplanned readmission were compared by
      treating medical unit adjusting for the four risk factors: severity, comorbidity,
      sex and age. A significant difference in risk-adjusted deaths and length of stay
      occurred among units treating heart failure, in length of stay among units
      treating renal failure, and in deaths among units treating gastrointestinal
      haemorrhage. A significant difference in death, length of stay and unplanned
      readmission occurred among units treating stroke. No significant difference in
      outcomes occurred among units treating myocardial infarction. Outcomes were
      predicted by age, severity and comorbidity. In conclusion, severity and
      comorbidity together with age were shown to be good predictors of outcomes. The
      methodology is considered unsuitable as a regular quality assurance activity.

PMID- 9010821
TI  - Medical general practice: influencing clients' levels of satisfaction.
AB  - A general practice consultation involves a variety of doctor-client interactions.
      Commonly, a diverse range of clients attend a general practice. Further, general
      practices vary in their design and in service provision. There are significant
      risks that clients' experiences may not match prior expectations, resulting in
      lower levels of satisfaction with the consultation. This study describes the
      pilot testing of the widely used Model of Service Quality adapted to a general
      practice context. The results suggest that the adapted model may be used to help
      improve practice design and, consequently, client satisfaction with the service
      provided.

PMID- 9010822
TI  - Clinical indicators in colorectal surgery.

PMID- 9010823
TI  - Do changes in the stereotypic depiction of a lesbian couple affect heterosexuals'
      attitudes toward lesbianism?
AB  - This study tested the hypothesis that heterosexuals with traditional sex role
      values would be less negative toward lesbians after reading a nonstereotypical
      description of a lesbian couple as opposed to a stereotypical description. Two
      experiments were conducted to assess stereotypes of lesbian couples and to test
      the hypothesis. Consistent with the hypothesis, traditional males showed
      significantly more positive attitudes toward lesbians as a result of exposure to
      less stereotypical depictions of couples. For nontraditional males treatments
      were ineffective, as expected. Counter to the hypothesis, exposure to
      nonstereotypical depictions of lesbian couples had no significant effect on
      traditional or nontraditional females' attitudes toward lesbians.

PMID- 9010824
TI  - Comparing the impact of homosexual and heterosexual parents on children: meta
      analysis of existing research.
AB  - Courts determine custody and visitation on the basis of the "best interests of
      the child." Current judicial rulings in some jurisdictions reflect a bias against
      awarding custody or granting visitation rights to homosexual parents, favoring
      the heterosexual parent or heterosexual relative of the child(ren). Should the
      sexual orientation of the parent play a part in the determination of custody or
      visitation in order to protect the child? This meta-analysis summarizes the
      available quantitative literature comparing the impact of heterosexual and
      homosexual parents, using a variety of measures, on the child(ren). The analyses
      examine parenting practices, the emotional well-being of the child, and the
      sexual orientation of the child. The results demonstrate no differences on any
      measures between the heterosexual and homosexual parents regarding parenting
      styles, emotional adjustment, and sexual orientation of the child(ren). In other
      words, the data fail to support the continuation of a bias against homosexual
      parents by any court.

PMID- 9010825
TI  - Sources of coming out self-efficacy for lesbians.
AB  - The empirical literature on disclosing a lesbian sexual orientation has explored
      the circumstantial and demographic variables related to this act. This
      exploratory study utilized self-efficacy theory (Bandura, 1986) to investigate
      the extent to which each of the four sources of efficacy information (e.g.,
      performance accomplishments, vicarious experience, verbal persuasion, or
      emotional arousal) contributed to the coming out self-efficacy of lesbians, that
      is, the sense of confidence possessed by a lesbian to disclose her sexual
      orientation to others. Anonymous survey packets were completed by 134 lesbians.
      Results of regression analyses indicated that emotional arousal was the most
      potent predictor of coming out self-efficacy. Verbal persuasion and vicarious
      experience also were significant. The most theoretically salient source of self
      efficacy information, performance accomplishments (Bandura, 1986), was not a
      significant predictor of coming out self-efficacy. Further, significant
      correlations were found between coming out self-efficacy and outness and life
      style satisfaction, which were also significantly correlated to measures of
      psychological adjustment.

PMID- 9010826
TI  - Validation of an inclusive model of sexual minority identity formation on a
      sample of gay men.
AB  - This article outlines the preliminary validation of a new, inclusive model of
      sexual minority identity formation (McCarn & Fassinger, 1996) on a sample of gay
      men. The model hypothesizes two separate but reciprocal processes of individual
      sexual identity development and group membership identity development in a four
      phase developmental sequence. The model was developed and successfully validated
      on a sample of lesbians (briefly described here), and the present study
      replicates and extends this work, using a modified Q-sort methodology, on a
      sample of 34 diverse gay men. Results indicated support for the model, in terms
      of both individual and group processes as well as phases, and suggested that the
      model is applicable to gay men. Implications of the study for theory, research,
      and practice are discussed.

PMID- 9010827
TI  - An empirical study of the beliefs of psychoanalysts about scientific and clinical
      dimensions of male homosexuality.
AB  - Eighty-eight clinical psychoanalysts responded to a questionnaire that assessed
      their theoretical beliefs about homosexuality. Questions were designed to asses
      agreement or disagreement with a model that homosexuality is pathological. Most
      psychoanalysts endorsed a nonpathological model, although their responses were
      sometimes inconsistent. We discuss the significance of these findings.

PMID- 9010828
TI  - Internalized homophobia in a sample of HIV+ gay men, and its relationship to
      psychological distress, coping, and illness progression.
AB  - The purpose of this study was to determine whether internalized homophobia is
      related to psychological distress and coping style and whether these
      relationships are moderated by illness stage. A sample of gay men, most of whom
      were HIV+, Caucasian, and well educated, were administered assessments at both
      baseline and 2-year follow-up, which allowed for the assessment of change over
      time in the context of HIV illness progression and to determine whether
      internalized homophobia predicts psychological distress and coping over time.
      Greater internalized homophobia at baseline, specifically among those who were
      HIV+ asymptomatic, predicted higher levels of distress at follow-up. In contrast,
      internalized homophobia had, at best, a weak association with coping. No
      relationship was found between illness stage and internalized homophobia,
      psychological distress, or coping. Mental health professionals working with HIV+
      gay men may be more effective in targeting resources and interventions aimed at
      improving mental health and quality of life if they address issues related to
      internalized homophobia.

PMID- 9010829
TI  - Comparative antioxidant effects of beta-adrenoceptor blockers, calcium
      antagonists and U-74500A against iron-dependent lipid peroxidation in murine
      ventricular microsomal membranes.
AB  - Recently we have shown that ACE inhibitors and platelet activating factor
      antagonists inhibit iron-dependent lipid peroxidation in murine ventricular
      membranes and possess beneficial effects on ischemia and ischemia reperfusion
      induced myocardial injury, which has been ascribed to their capacity to scavenge
      or impair oxygen free radical generation. In the present study we investigated
      the effects of beta-adrenoceptor blockers and calcium antagonists on iron
      dependent lipid peroxidation (LPO) in murine ventricular membranes and compared
      them with the lazaroid U-74500A, a potent antioxidant. Fe(2+)-vitamin C induced
      LPO in a concentration- and time-dependent manner, measured as thiobarbituric
      acid reactive substances (TBARS) formation. Pretreatment of ventricular membranes
      with gallopamil, verapamil, propranolol and metaprolol at concentrations of 5
      microM and higher inhibited Fe(2+)-vitamin C-induced LPO in a concentration
      dependent manner with IC50 values of 192.8-208.3 microM; however, they were less
      potent than U-74500A (IC50 6.8 microM). In contrast, atenolol, timolol, diltiazem
      and nifedipine inhibited LPO at very high concentrations with IC50 values of
      864.5-971.5 microM. Inhibition of LPO may not be due to the drugs' classical
      pharmacological actions, but rather to their characteristic chemical structures
      or physicochemical interactions with biological membranes. In view of the
      pathological importance of LPO in cardiac ischemic injury, inhibition of LPO by
      gallopamil, verapamil, propranolol and metaprolol may provide additional
      cardioprotective activity and thus reinforces their beneficial effects in the
      treatment of ischemic heart disease.

PMID- 9010830
TI  - Effects of opioid-type stressors on serum digoxin-like immunoreactivity in rats.
AB  - The effects of opioid-type stressors (immobilization, electric footshock and
      forced swimming) on serum digoxin-like immunoreactivity (SDLI) were investigated
      in rats. All of the stressors significantly elevated the SDLI. Naloxone treatment
      after application of stressors prevented the elevation of SDLI, whereas naloxone
      treatment alone did not cause any significant changes. The observed increase in
      SDLI in this study may be attributed to the actions of endogenous opioid peptides
      released during stress.

PMID- 9010831
TI  - Effects of nicotine and exposure to cigarette smoke on suppression of local graft
      versus-host reaction induced by immobilization stress in mice.
AB  - To study the effects of emotional stress on immunological activities and
      modification of these effects by nicotine or cigarette smoke, we evaluated the
      effects of immobilization stress on local graft-versus-host (GVH) reaction, a
      cell-mediated immune response, and the effects of nicotine and cigarette smoke on
      them. The effects of immobilization stress on GVH reaction and the effects of
      nicotine and cigarette smoke on them were evaluated in two experiments: in
      Experiment 1 by applying the stimulations before and immediately after spleen
      cell transplantation, and in Experiment 2, by applying stimulations after
      transplantation. Spleen cells of BALB/C mice were injected into the footpad of
      CBF1 mice, and GVH reaction was examined after 7 days by weighing the popliteal
      lymph nodes. Immobilization, nicotine administration and inhalation of cigarette
      smoke were performed either for 5 days before and immediately after the
      transplantation (Experiment 1) or for 5 days after transplantation (Experiment
      2). The weight of the lymph nodes was markedly increased in the control group,
      indicating GVH reaction, but the reaction was suppressed by immobilization in
      both experiments. This suppression of GVH reaction by immobilization was
      antagonized by nicotine administration and exposure to cigarette smoke in
      Experiment 1 but not in Experiment 2. These findings suggest that nicotine and
      cigarette smoke induce recovery of immune response suppressed by immobilization
      stress, especially by increasing the competence of antigen recognition.

PMID- 9010832
TI  - Epileptogenic activity induced by combined treatment with antiinflammatory drugs
      and enoxacin and its inhibition by a calcium antagonist, nicardipine.
AB  - Epileptogenic activity induced by combined treatment with antiinflammatory drugs
      and enoxacin was investigated in chronic electrode-implanted rats. Ferubinac
      ethyl and aspirin DL-lysine showed a spike and wave complex in EEG without
      showing remarkable behavioral changes when they were injected intraventricularly,
      although a relatively high dose was needed. Enoxacin, on the other hand, elicited
      potent epileptogenic activity characterized by uninterrupted high voltage spike
      and wave complex at doses of 50 and 100 micrograms. At the same time, rats showed
      hyperactivity, jumping and violent convulsion. Combined treatment with enoxacin
      (p.o.) and ferubinac ethyl (i.v.) caused potent epileptogenic activity
      characterized by uninterrupted burst of high voltage spike and wave complex.
      Behaviorally, animals showed forelimb clonus, head nodding and generalized
      convulsion. High voltage spike and wave complex was also observed after combined
      treatment with enoxacin (i. vent.) and ferubinac ethyl (i.v. or i. vent.) in
      association with hyperactivity and jumping and violent convulsion. Nicardipine
      remarkably inhibited epileptic seizures induced by combined treatment with
      enoxacin (p.o.) and ferubinac ethyl (i.v.). It is concluded that simultaneous
      treatment with enoxacin and ferubinac ethyl produced epileptogenic activity when
      injected intraventricularly, and nicardipine inhibited convulsions induced by
      combined use of enoxacin (p.o.) and ferubinac ethyl (i.v.).

PMID- 9010833
TI  - The effects of triethanolamine myristate, a fatty acid salt, on the
      bioavailability of riboflavin in dogs.
AB  - A study in dogs was performed in which a physiologic approach to delaying gastric
      emptying was examined. Triethanolamine myristate (a fatty acid salt) was used to
      delay gastric emptying in hopes of increasing the bioavailability of riboflavin.
      A bilayer tablet consisting of triethanolamine myristate and riboflavin resulted
      in an absolute bioavailability of 2-3 times greater than the bioavailability of
      riboflavin alone. Increases in bioavailability although to a lesser extent, were
      also seen with the 30 min pretreatment with triethanolamine myristate. The
      results suggest that it was possible to delay gastric emptying.

PMID- 9010835
TI  - Current concepts in the molecular diversity and pharmacology of dopamine
      receptors.

PMID- 9010834
TI  - Aldosterone response to metoclopramide in patients with prolactinoma: effect of
      short-term bromocriptine treatment.
AB  - The acute effect of 10 mg metoclopramide i.v. on prolactin and aldosterone levels
      was studied in 8 women with prolactinoma and 8 normal women. The prolactin
      response to metoclopramide was blunted in hyperprolactinemic patients in
      comparison with controls. Metoclopramide induced similar aldosterone increases in
      patients and controls, but hyperprolactinemic women showed a more sustained
      aldosterone response. Bromocriptine treatment (10 mg daily p.o. for 5 days) in
      patients with prolactinoma completely suppressed the prolactin response to
      metoclopramide and the aldosterone response curve was very similar to that of
      controls. The results did not exclude some degree of suppression of aldosterone
      in response to bromocriptine.

PMID- 9010836
TI  - Rat cell cultures: experimental models to study neurodegenerative disorders and
      new pharmacological compounds.

PMID- 9010837
TI  - The Schistosoma mansoni epidermal growth factor receptor homologue, SER, has
      tyrosine kinase activity and is localized in adult muscle.
AB  - DNA encoding the full-length Schistosoma mansoni epidermal growth factor
      receptor, SER, was obtained by combining partial cDNA clones. Three different
      anti-SER antibody preparations, specific either to the SER amino-terminus or the
      predicted ligand binding domain were generated with recombinant or synthetic
      peptides and purified by antigen affinity. Recombinant SER was expressed within
      insect cells using the baculovirus expression system and detected by each of the
      anti-SER antibodies as well as anti-phosphotyrosine antibodies. By in vitro
      phosphorylation of immunoprecipitated recombinant SER, the protein has been shown
      to be capable of tyrosine autophosphorylation but this activity is not affected
      by human epidermal growth factor. Native SER is detected as a 170 kDa protein in
      Western blots of S. mansoni adult worm membrane preparations. Adult worm
      sections, labeled with anti-SER antibodies, localize SER predominantly to the
      muscle of adult male and female worms. These results confirm a place for SER in
      the EGFR family of tyrosine kinases and strongly suggest that it participates in
      schistosome signal transduction, perhaps related to muscle development or
      function.

PMID- 9010838
TI  - Human and fungal 3' splice sites are used by Trypanosoma brucei for trans
      splicing.
AB  - In Trypanosoma brucei, pre-mRNAs are joined to a 5' 39 nt spliced leader sequence
      by trans splicing, a process that has not been well characterized. We have asked
      whether the 3' splice site regions of human and yeast introns are able to
      substitute in vivo for the 3' spliced leader acceptor regions of trypanosome pre
      mRNA sequences. The ability of heterologous sequences to participate in trans
      splicing in trypanosomes was assayed by chloramphenicol acetyltransferase (CAT)
      enzyme activity and/or the detection of spliced CAT mRNA. Four out of the six
      heterologous 3' splice site regions (human beta-globin intervening sequence
      (IVS)2, human c-myc IVS2, human factor-VIII IVS1, and yeast actin IVS) functioned
      as 3' spliced leader acceptor regions in T. brucei, while two did not show
      significant or detectable levels of CAT activity (human beta-globin IVS1 and
      human c-myc IVS1). In the case of the human beta-globin IVS1 however, lengthening
      of the polypyrimidine tract as a result of single purine to pyrimidine
      transversions produced an active acceptor in which the spliced leader addition
      site coincides with the 3' splice site of the beta-globin exon 2. These studies
      indicate that some, but not all 3' acceptor regions in humans can function as
      spliced leader addition sites in trypansomes.

PMID- 9010839
TI  - Further characterization of a 58 kDa Plasmodium berghei phosphoprotein as a
      cochaperone.
AB  - Molecular chaperones are important for proper protein folding during protein
      biogenesis. This report describes a protein from Plasmodium berghei which is 30%
      identical and 40% similar to a recently described mammalian cochaperone, or heat
      shock protein 70 interacting protein. The P. berghei cochaperone accumulates
      throughout the trophozoite stage and decreases during the schizont stage. The
      stage specific expression is consistent with its presumed role in protein folding
      or protein-protein interactions. The largest difference between the Plasmodium
      and mammalian sequences is a more extensive domain of imperfect glycine-glycine
      methionine-proline (GGMP) tandem repeats in the parasite's cochaperone sequence.
      Immunofluorescence studies show that the protein is an abundant cytosolic protein
      of the parasite. However, antibodies raised against the GGMP repeat domain, which
      is also found in other parasite chaperones, react with both the parasite and host
      erythrocyte membrane. The reactivity with the host membrane suggests that the
      parasite exports molecular chaperones into the infected erythrocyte.

PMID- 9010840
TI  - In vitro selection of halofantrine resistance in Plasmodium falciparum is not
      associated with increased expression of Pgh1.
AB  - Recent investigations into quinoline and phenanthrene methanol resistance in
      Plasmodium falciparum have described a linkage between amplification of the mdr
      homologue pfmdr1 and decreased susceptibility to mefloquine (MQ) and halofantrine
      (HF). We have examined the current theories on cross-resistance patterns and
      pfmdr1 gene expression by comparing the chloroquine (CQ) resistant isolate K1
      with K1Hf, developed from the K1 isolate by intermittent exposure to
      halofantrine. Reduced halofantrine susceptibility in K1Hf was accompanied by
      reduced sensitivity to mefloquine and increased sensitivity to chloroquine. These
      sensitivity changes were reflected by changes in parasite drug accumulation. The
      loss of high level chloroquine resistance in K1Hf was associated with an
      inability of verapamil to enhance chloroquine sensitivity or accumulation. In
      contrast verapamil retained the chemosensitising potential against quinine in
      this isolate. The changes in phenotype were achieved without any amplification or
      increased expression of pfmdr1 or reversion of the Tyr86 mutation in the gene.
      Our data indicates that acquisition of halofantrine and mefloquine resistance and
      the loss of high level chloroquine resistance can be achieved without enhanced
      expression of the pfmdr1 gene product.

PMID- 9010841
TI  - Molecular characterization of two species-specific tandemly repeated DNAs from
      entomopathogenic nematodes Steinernema and Heterorhabditis (Nematoda:Rhabditida).
AB  - Two AluI tandemly repeated DNAs were cloned from two entomopathogenic nematodes:
      the first one from Steinernema glaseri and the second one from Heterorhabditis
      bacteriophora. The monomeric units of these two satellite DNAs have a repeat
      length of 174 and 168 bp, respectively. These AluI repeated element families
      appear to constitute 5.5% of the S. glaseri genome and 5% of the H. bacteriophora
      genome. Their A + T contents were estimated at 55% and 57%. Moreover, the
      monomers of these two families are quite homogeneous in sequence, showing, on
      average, 3.9% and 2.7% divergence from their respective consensus sequence. These
      results suggest that some mechanism is acting to maintain the homogeneity of
      these repeated DNAs despite their abundance. We have also shown that these two
      DNA families are species-specific and therefore could be used for the
      identification of Steinernema and Heterorhabditis entomopathogenic nematode
      species.

PMID- 9010842
TI  - Nuclear calcium flux in Trypanosoma brucei can be quantified with targeted
      aequorin.
AB  - The following study was undertaken to determine if calcium ions move from the
      plasma membrane to the nucleus of Trypanosoma brucei. Nuclear and cytosolic
      calcium flux was measured with the calcium sensitive photoprotein, aequorin which
      was targeted to various locations in stably transformed procyclic cells.
      Immunoblots revealed that the recombinant proteins, CYT-AEQ and NUC-AEQ were
      translated in transformants, and that CYT-AEQ was contained in a soluble
      fraction. Immunolocalization demonstrated that NUC-AEQ was contained within the
      trypanosome nucleus. To evaluate calcium movement from the plasma membrane to the
      nucleus in live trypanosomes, aequorin was reconstituted in vivo with
      coelenterazine and luminescence was recorded. The resting levels of [Ca2+]cyt and
      [Ca2+]nuc were similar (314 +/- 43 and 287 +/- 28 nM, respectively). When calcium
      influx across the plasma membrane was initiated with 2 microM ionomycin,
      [Ca2+]cyt and [Ca2+]nuc each became elevated in parallel to a new steady state
      which was approximately 2-fold above the resting level. Compound 48/80 initiated
      a calcium flux across the plasma membrane by a different mechanism from
      ionomycin, and in a manner that was inhibited by the calcium channel antagonist,
      La3+. Compound 48/80 (8 micrograms/ml) transiently elevated [Ca2+]cyt to 1.73 +/-
      0.3 microM over the course of 20 s, and also generated a transient rise in
      [Ca2+]nuc which peaked at 1.32 + 0.29 microM over the same time course. Overall,
      these data demonstrate that calcium moves into and out of the trypanosome nucleus
      in a manner which closely parallels changes in [Ca2+]cyt. A small calcium ion
      gradient between nucleus and cytoplasm was also observed.

PMID- 9010843
TI  - Functional analysis of the Schistosoma mansoni 28 kDa glutathione S-transferase
      gene promoter: involvement of SMNF-Y transcription factor in multimeric
      complexes.
AB  - The ability of the 5' flanking region of the gene encoding the 28 kDa glutathione
      S-transferase of Schistosoma mansoni gene to promote transcription, was studied
      in different mammalian cell lines. Results of transient transfection assays
      showed a strong activity of the -277 to +1 nt region of the Sm28GST gene,
      comparable to that of well-studied promoters. Deletion analysis indicated that an
      AP-1 site and two closely located CCAAT (Y1 and Y2) boxes were the principal
      motifs responsible for the promoter activity. Binding of the NF-Y complex to Y1
      and Y2, as well as to a third CCAAT box (Y3) close to the promoter TATA box, was
      compared in gel shift and super-shift experiments. All of the three Y boxes bound
      protein complexes from S. mansoni nuclear extracts that were shown to contain the
      A subunit of the schistosome NF-Y complex (SMNF-YA). Competition assays revealed
      a differential affinity of the Y1, Y2 and Y3 sequences for NF-Y. The Y1, Y2 and
      Y3 regions were also shown to activate transcription when included in an
      heterologous promoter and data obtained strongly suggested the involvement of
      SMNF-Y in multimeric complexes during this process.

PMID- 9010844
TI  - Stable coexpression of a drug-resistance gene and a heterologous gene in an
      ancient parasitic protozoan Giardia lamblia.
AB  - Manipulation of gene expression in Giardia lamblia, one of the most ancient
      eukaryotes, may provide insights into the evolutionary transition from
      prokaryotes to eukaryotes. Two recent successes in transient expression of the
      firefly luciferase (luc) gene in G. lamblia were mediated by a 5'-untranslated
      region (UTR) of the Giardia glutamate dehydrogenase (gdh) gene and a giardiavirus
      (GLV) genomic transcript, respectively. We now report a stable coexpression of
      luc gene with a neomycin phosphotransferase (neo(r)) gene in G. lamblia. An in
      vitro transcript of the construct pC670-Neo; containing the neo(r) encoding
      region flanked with the 5'670 nucleotides (nt) and the 3'2022 nt portion of GLV
      positive strand RNA, was electroporated into G. lamblia trophozoites that were
      infected with GLV. G418-resistant Giardia trophozoites were cloned, and the
      neo(r) mRNA in these clones was found to increase with increasing G418 pressure.
      This drug resistance remained stable upon continuous in vitro cultivation in the
      absence of G418 for over 15 days. Another plasmid pNeo/GDH/Luc, was constructed
      by inserting luc gene downstream from the neo(r) gene and the 193 nt 5' portion
      of gdh gene in pC670-Neo, and its bicistronic in vitro transcript was introduced
      into GLV-infected G. lamblia by electroporation. The transfectants demonstrated
      G418-resistance and persistent luciferase activity at levels parallel to the
      amount of G418 used for selection, peaking at a level of several thousand-fold
      above the background. Taken together, these data indicate that the neo(r) gene
      provides an effective selection marker for transformation of Giardia
      trophozoites, and the bicistronic RNA transfection vector may open the way for
      functional analysis of other genes in Giardia.

PMID- 9010845
TI  - Chemical synthesis of the Plasmodium falciparum dihydrofolate reductase
      thymidylate synthase gene.
AB  - Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a
      well-known target for pyrimethamine and cycloguanil. The low amounts of enzyme
      obtainable from parasites or the currently available heterologous expression
      systems have thus far hindered studies of this enzyme. The 1912-base pair P.
      falciparum DHFR-TS gene was designed based on E. coli codon preference with
      unique restriction sites evenly placed throughout the coding sequence. The gene
      was designed and synthesized as three separated domains: the DHFR domain, the
      junctional sequence, and the TS domain. Each of these domains contained numerous
      unique restriction sites to facilitate mutagenesis. The three domains were
      assembled into a complete DHFR-TS gene which contained 30 unique restriction
      sites in the coding sequence. The bifunctional DHFR-TS was expressed from the
      synthetic gene as soluble enzyme in E. coli about 10-fold more efficiently than
      from the wild-type sequence. The DHFR-TS from the synthetic gene had kinetic
      properties similar to those of the wild-type enzyme and represents a convenient
      source of protein for further study. The unique restriction sites in the coding
      sequence permits easy mutagenesis of the gene which should facilitate further
      understanding of the molecular basis of antifolate resistance in malaria.

PMID- 9010846
TI  - Identification and localization of rab6, separation of rab6 from ERD2 and
      implications for an 'unstacked' Golgi, in Plasmodium falciparum.
AB  - The rab6 gene product in mammalian cells and yeast is localized to and regulates
      protein transport in the medial and trans Golgi cisternae, as well as the trans
      Golgi network. We have identified a homologue in the malaria parasite Plasmodium
      falciparum which displays a rab-like sequence that is 62.4% identical to
      mammalian rab6. In addition the parasite gene (Pfrab6 gene) contains an N
      terminal hydrophobic domain, unique to P. falciparum. Antibodies developed to
      Pfrab6 localize protein in 4-7 well-resolved sites in a ring-stage parasite, as
      detected by high resolution fluorescence microscopy. This suggests that there are
      multiple, distinct foci of medial/trans Golgi membranes in a ring. ERD2 is a cis
      Golgi marker in mammalian cells. The plasmodial homologue of ERD2 (PfERD2) is
      concentrated in a single perinuclear region in a ring-stage parasite. This site
      is distinct from the Pfrab6 membranes, indicating that early and late Golgi
      markers can be segregated in P. falciparum. Mammalian cells contain a single
      Golgi complex where cis medial and trans markers are tightly stacked in closely
      apposed cisternae. In P. falciparum-rings however, rab6-associated membranes are
      not invariably 'stacked' with an ERD2 structure. In immunoelectron microscopy
      studies, both the PfERD2- and Pfrab6-associated membranes appear tubulovesicular
      in nature, devoid of cisternal morphology. Hence the Golgi of ring stage
      parasites may comprise of multiple, 'unstacked' tubulovesicular clusters,
      suggesting a primitive organization of the organelle in Plasmodia.

PMID- 9010847
TI  - Identification and characterization of the Meloidogyne incognita col1 cuticle
      collagen gene.

PMID- 9010849
TI  - [Current status and future prospect of organ transplant network in Japan].
AB  - Transplant network plays a indispensable role in the organ transplantation, which
      consists of the registration of patients, collection of donor information,
      recipient selection and shipping of the organs, retrieval of transplant data and
      their analysis. Since 1977 the cadaveric kidney transplantation have had been
      done in the kidney transplant network, which was run by National Sakura Hospital
      as the transplant center and 14 subcenters. As the number of cadaveric kidney
      transplantation, however, was decreased year by year since 1989, there raised
      some problems, such as allocation policy of kidney grafts, lack of standardized
      HLA examination and review system, management within each administrative district
      and so on. Based upon the report of ad hoc committee of the Multiorgan Transplant
      Network, there substituted the new kidney transplant network system, Japan Kidney
      Transplant Network for the former kidney transplant network since 1995. The new
      system is operated not only by transplant surgeon, but by transplant
      coordinators, nephrologists, doctors in charge of dialysis therapy,
      representatives of kidney bank and other organizations/associations, and others.
      After the legislation of the transplant act, the network will be reorganized into
      the network system for multiorgan sharing. To establish the multiorgan sharing
      network, uniform protocol of multiorgan procurement, insurance of informed
      consent, propagation of donor cards for multiorgan donation, registration for
      waiting lists, allocation system for other organs than kidney, and education of
      transplant coordinator for multiorgan procurement are required.

PMID- 9010848
TI  - Cloning, sequencing, and functional activity of the Trypanosoma brucei brucei
      alternative oxidase.

PMID- 9010850
TI  - [Organ Preservation].
AB  - Organ procurement is the first step of organ preservation. We have developed "in
      situ machine wash out technique with CMH solution" for the purpose of rapid
      cooling and complete elimination of blood. The utility of this technique was
      confirmed by both experimentally and clinically. Two major techniques have been
      used for organ preservation. One is a simple cold storage. Using this method, it
      is easy to transport organs for transplantation. In addition, availability of UW
      solution is another advantage of this method. The other is a continuous
      hypothermic perfusion. Despite of complexity and difficulty of organ
      transportation, this technique has some advantages, such as viability assay and
      pretreatment of organs before transplantation. In our experimental studies,
      viability assays of canine liver and pancreas were achieved using a organ
      perfusion machine. We also succeeded to prolong the survival of canine pancreatic
      allograft by pretreatment of anti-Ia antibody during perfusion. While,
      cryopreservation is most suitable for cell preservation like pancreatic islets.
      Recently, gene technology was applied for organ preservation studies. In the
      future, this might become a potent tool for studies in this field.

PMID- 9010851
TI  - [Transplantation immunology and immunosuppressive drug].
AB  - Tyrosine kinases (TK) and G proteins act as second, messengers for intracellular
      signal transduction. TK activates the cascade of protein phosphorylation. G
      proteins are heterodimer complex with alpha, beta, and gamma subunits. PLC
      activated by GTP-binding alpha subunit lyses membrane phosphatidyl inositol (PI),
      releasing diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 releases
      calcium into cytoplasm to activate calcineurin, causing a NF-AT cytoplasmic
      factor (NF-ATc) to translocate to nucleus. DAG activates protein kinase C (PKC),
      which synthesizes another nuclear factor NF-ATn. When NF-ATc and NF-ATn assemble
      to form the complex on the promoter site of DNA, transcription of IL-2 mRNA
      begins. PKC also induces phosphorylation of I-kappa B to release NF-kappa B. The
      complex of CsA or FK506 with CyP or FKBP, respectively, inhibits the activation
      of calcineurin. FKBP-binding rapamycin inhibits cell proliferation and
      differentiation by inactivation of p70 s6 kinase. RS61443 and mizoribine
      influence specifically on the de novo pathway of purine biosynthesis. DSG may
      bind to Hsc 70 and inhibit the translocation of NF-kappa B into nucleus. FTY720
      induces lymphocyte-specific apoptosis, independently on Fas-antigen expressions.
      by modulating bcl-2 genes.

PMID- 9010852
TI  - [Organ transplantation. 4. Renal transplantation].
AB  - Renal transplantation is well recognized as a better modality for improving
      quality of life (QOL) in patients with end stage renal disease as compared with
      hemodialysis. The better QOL attained by renal transplantation can be maintained
      as far as a renal allograft functions. The results of renal transplantation have
      been markedly improved mainly by introducing cyclosporine (CsA), especially using
      regimens in which a more decreased dose of CsA is used in combination with other
      immunosuppressive drugs, including azathiopurine and ALG to avoid nephrotoxicity
      of CsA. Mortality due to a variety of complications such as infections, hepatic
      failure, malignancy and cardiovascular diseases aggravates the results of renal
      transplantation. Although the result of Kidney transplantation in Japan is as
      good as that observed in European countries ane the United States, a number of
      transplantation performed in Japan is extremely small compared with these
      countries. In order to increase a number of renal transplantation in Japan, all
      efforts aiming at promoting cadaveric kidney donation should be performed as a
      first priority.

PMID- 9010853
TI  - [Liver transplantation--present status].
AB  - Living related liver transplantation (LPLT) as well as reduced sized graft or
      split liver transplantation has come from the situation with donor shortage for
      conventional whole liver transplantation from brain dead donors (cadaveric liver
      transplantation; CLT). To date, about fifty thousands liver transplants have been
      undergone all over the world. CLT has much diversity of the original diseases,
      but mainly liver cirrhosis in adults and biliary atresia in children. Original
      diseases for LRLT have been deviated to cholestatic diseases in childhood, but
      now LRLT for adults and other diseases in children, i.e. fulminant hepatitis and
      metabolic disorders, are increasing. The survival rate of LRLT in Kyoto
      University for first 230 consecutive cases was 79.5%. The main cause of death was
      infection-related events. There are several problems in LRLT to be resolved;
      perioperative management of infectious complications, how to deal with the
      unavoidable ABO incompatible matching transplants, how to expand the national
      capacity of LRLT to respond the urgent transplantations. Earlier establishment of
      CLT program in Japan will be necessary to make the liver transplantation the
      beneficial procedure for more people with end stage liver diseases.

PMID- 9010854
TI  - [Pancreas and islet transplantations].
AB  - Pancreas transplantation has been established as a treatment option for type I
      diabetes mellitus with one-year patients survival rate of 91% and one-year graft
      survival rate of 71%. Simultaneous pancreas and kidney transplantation with the
      bladder-drainage technique is most frequently performed. The bladder drainage
      technique makes amylase activity measurement in the urine as well as urine
      cytology possible, which facilitate a diagnosis of acute rejection. Combination
      treatment with cyclosporine, azatioprine, steroid and anti-lymphocyte globulin is
      usually employed for immunosuppression. In addition, FK506 in now available and
      expected to contribute to better graft survival. In contrast, islet
      transplantation has not yet achieved satisfactory results. Although a large
      number of islets can now be obtained from one pancreas, they are not sufficient
      for stabilizing a diabetic condition and multiple donors are still required. Xeno
      transplantation may resolve the problem. Both pancreas and islet transplantation
      will achieve better results with further advance of transplant techniques
      including immunosuppressive treatment and diagnostic methods for acute rejection.

PMID- 9010855
TI  - [Heart transplantation].
AB  - Heart transplantation was introduced clinically in 1964 by Hardy using a
      Chimpanzee heart. Since the standard method had been established by Shumway and
      cyclosporine had been introduced in 1982, patient numbers increased rapidly.
      Because of donor shortage, patient numbers have been about 3,000 to 3,500 in
      these 8 years. According to the registry of the International Society for Heart
      and Lung Transplantation, 1 and 3 year survival rate were 80% and 73%,
      respectively. We hope to start heart transplantation as soon as possible in
      Japan.

PMID- 9010856
TI  - [Present international status and basic approach of lung and heart-lung
      transplantation].
AB  - Lung transplantation has been established as an optional treatment for variable
      irreversible diffuse lung diseases. To date, more than 5,000 patients have
      underwent lung transplantation, and nearly 1,000 procedures a year are performed
      recently. Although heart-lung transplantation has also been technically
      established, this procedure is confined to quite limited conditions due to the
      severe shortage of donors and many difficulties in operative procedure and the
      patient management. Preservation, post-transplantation edema, diagnosis of
      rejection, chronic rejection, shortage of donor organs, are principal problems in
      clinical lung transplantation, 24-hour preservation proved to be possible in
      several recent experimental studies, and the reperfusion injury has been revealed
      to be one of causes of post-transplantation edema. Establishment of methods for
      long-term pulmonary preservation and for the treatment of post-transplantation
      edema may be promising in the near future. Shortage of donor lung is one of major
      limiting factors. Research works on xenotransplantation and cadaver lung
      transplantation are on going, and these may help in solving this problem.

PMID- 9010857
TI  - [Clinical intestinal transplantation at the University of Pittsburgh: an update].
AB  - From May 1990 until August 1996, 87 patients received 92 intestinal
      transplantation, including an isolated graft (n = 33), combined liver and
      intestinal grafts (n = 41), and abdominal multivisceral grafts (n = 13). There
      were 52 children (mean age 3.3 years) and 35 adult patients (mean age 32.6
      years). Of these, 29 patients received the colon as a composite of the intestinal
      graft, and 11 recent patients were given unmodified donor bone marrow cells
      simultaneously. Postoperative immunosuppression was with Tacrolimus and low-dose
      steroids, to which either azathioprine, mycophenolate, or cyclophasphamide was
      added supplementarily. One-, three-, and five-year patient and graft survival was
      73% and 64%, 44% and 36%, and 444% and 36%, respectively. There was no
      statistical difference in patient and graft survival after different types of
      intestinal transplantation. Although overall patient and graft survival did not
      differ between pediatric patients and adult recipients, isolated graft survival
      children was higher than that of adult recipients (57% versus 11% at three
      years). Transplantation of the grafts from CMV seropositive donors and the
      inclusion of the colon in the intestinal graft worsened the survival in adult
      recipients, but not in children. The influence of simultaneous bone marrow
      transplantation on the outcome is undetermined due to the short follow-up period.
      Intestinal transplantation has become feasible, but still requires improved
      immunosuppression and graft dysmotility management to be a clinical practice.

PMID- 9010858
TI  - [Xenotransplantation].
AB  - A Bulk of studies on xenotransplantation have been accumulated for the last few
      years. Most of the studies focus in the investigation for etiologic mechanism of
      hyperacute rejection seen in the xenotransplantation between distant species.
      Underlying pathophysiology in hyperacute rejection is primarily based on initial
      antigen-antibody reaction between oligosaccharide epitope of the xenogeneic organ
      and natural antibody in the recipient plasma. Subsequent activation of complement
      cascade and activation of the endothelial cell constitute an integral part of the
      entire complexity of the hyperacute rejection. We herein summarize the updated
      knowledge and provide an overview on this interesting research field.

PMID- 9010859
TI  - [A case of internal supravesical hernia].
AB  - We report a case of internal supravesical hernia. A 74-year-old male with
      complaint of abdominal pain underwent an operation for small intestinal
      obstruction due to its incarceration into the internal supravesical hernia.
      Retrospectively, the preoperative abdominal CT film showed the relation of the
      incarcerated intestine, the urinary bladder, and the middle umbilical ligament.
      This is the first case of the internal supravesical hernia in which the
      preoperative CT had taken and it will contribute to the preoperative correct
      diagnosis in the future.

PMID- 9010860
TI  - New chemotherapy treatment options and implications for nursing care.
AB  - PURPOSE/OBJECTIVES: To review the drug profiles and nursing implications of
      Camptosar (irinotecan) (pharmacia & Upjohn, Inc., Kalamazoo, MI), Hycamtin
      (topotecan) (SmithKline Beecham Oncology,Philadelphia, PA), 9-aminocamptothecin
      TM (9-AC) (Pharmacia & Upjohn, Inc.), Taxotere (docetaxel) (Rhone-Poulenc Rorer
      Pharmaceuticals, Inc., Collegeville, PA), and Oncaspar (Rhone-Poulenc Rorer
      Pharmaceuticals). DATA SOURCES: Published articles, abstracts, drug
      manufacturers, personal experience with clinical trials of these agents. DATA
      SYNTHESIS: Camptosar's dose-limiting toxicity is diarrhea, which requires astute
      management. Hycamtin and 9-AC are severely myelosuppressive. Taxotere's use has
      been complicated by fluid retention and, to a lesser degree, hypersensitivity
      reactions. Oncaspar has the same toxicity profile as natural L-asparaginase with
      fewer hypersensitivity reactions. CONCLUSIONS: Research in the field of oncology
      continues to progress toward the cure of cancer. Novel agents offer promising new
      treatment options and affect response rates and patient care. Oncology nurses are
      challenged to stay abreast of these new developments. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses play a vital role in the assessment and management of treatment
      related side effects. Patient education regarding anticipated side effects and
      appropriate self-care measures are essential nursing functions.

PMID- 9010861
TI  - Outpatient chemotherapy: telephone triage for symptom management.
AB  - PURPOSE/OBJECTIVES: To describe the use of telephone triage in the management of
      chemotherapy-related patient problems. DATA SOURCES: Published articles, nursing
      texts, personal experience. DATA SYNTHESIS: With the impact of managed care and
      an increase in the number of patients being cared for at home, the need for a
      system of assessment and intervention that is not based on in-person visits is
      being recognized. Assessing patient symptoms over the phone and advising patients
      regarding appropriate care is being recognized as a common practice. CONCLUSIONS:
      With the use of established protocols for assessment and treatment, nurses can
      successfully manage many patient needs over the phone. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses play an active role in performing telephone triage and writing
      the appropriate protocols to facilitate safe and effective caregiving by phone.

PMID- 9010862
TI  - Neurologic, pulmonary, and cutaneous toxicities of high-dose chemotherapy.
AB  - PURPOSE/OBJECTIVES: To discuss dose-intensive chemotherapy and the associated
      toxicities to the nervous, pulmonary, and cutaneous systems. DATA SOURCES:
      Published articles, book chapters, and personal experience. DATA SYNTHESIS:
      Because of the discovery of the protective effect of colony stimulating factors,
      a renewed emphasis has been placed on dose-intensive chemotherapy in an attempt
      to affect both survival and cure rates with chemotherapy. As a result, increased
      toxicities have been seen in other organ systems. CONCLUSIONS: Toxicities to the
      nervous, pulmonary, and cutaneous systems are increasing. Meticulous medical and
      nursing care are critical to ensure patient survival and to minimize these
      effects. IMPLICATIONS FOR NURSING PRACTICE: Goals of care include a through
      knowledge of potential toxicities, recognition of signs and symptoms of toxicity,
      and appropriate nursing interventions once such deficits occur to decrease the
      toxic effects of chemotherapy and improve patient function.

PMID- 9010863
TI  - Nurse and patient satisfaction with three types of venous access devices.
AB  - PURPOSE/OBJECTIVES: To examine patient and nurse satisfaction with three types of
      venous access devices (VADs)--port, Groshong (Bard Access Systems, Salt Lake
      City, UT), and Hicman (Bard Access Systems)--and to identify the problems and
      benefits experienced with each type of device. DESIGN: A descriptive,
      correlational quality-assurance study. SETTING: An outpatient oncology/hematology
      clinic in a midwestern United States academic hospital with a comprehensive
      cancer center. SAMPLE: A convenience sample of 85 patients who had a port,
      Groshong catheter, or Hickman catheter and the clinic nurses who provided their
      care. METHOD: Consecutive patients meeting study criteria were invited to
      complete self-report questionnaires at the time of their clinic visits. Clinic
      nurses who cared for these patients also completed questionnaires. FINDINGS:
      Patients' reports of benefits did not differ by device, but they reported fewer
      blood-drawing problems with ports than with Groshong on Hickman catheters.
      Patients and nurses reported infections and clots more often with Groshong
      catheters than with the other two devices, Patients indicated that healthcare
      workers seemed most knowledgeable about Hickman catheters. Patients with ports
      reported more problems with access to the device, development of hematomas, and
      anxiety. Nurses reported more flow rate problems with Groshong catheters than
      with Hickman catheters. Patients and nurses reported no flow rate problems with
      ports. CONCLUSIONS: Each device was associated with a specific problem, yet in
      the global satisfaction ratings, patients expressed the greatest satisfaction
      with Hickman catheters and ports. Nurses tended to be least satisfied with
      Groshong catheters. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to ensure that
      other care providers have appropriate information on the care of VADs. This could
      be accomplished via written instructions on VAD care and followup telephone calls
      to care providers. A need exists for continued patient education on VAD care to
      minimize complications. The selection of an appropriate VAD should be based on
      the patient's best interests rather than on nurses' preferences.

PMID- 9010864
TI  - Safe handling of cytotoxic drugs in the physician's office: a procedure manual
      model.
AB  - PURPOSE/OBJECTIVE: To present a model of an adapted manual of safety procedures
      designed for education and implementation of standardized cytotoxic drug handling
      in the private oncology office setting. DATA SOURCES: Published articles,
      textbook chapters, published technical bulletins and guidelines, research studies
      identifying risks of occupational exposure and procedural guideline sources for
      reducing these risks. DATA SYNTHESIS: Most published guidelines on safe handling
      of cytotoxic drugs address the hospital setting but lack practical guidelines for
      use within an oncology office. The procedures presented in this model are a
      composite of several current guidelines offering recommendations for minimizing
      chronic low-level exposure to cytotoxic drugs. The recommendations are compiled
      into a procedure manual for office settings. CONCLUSIONS: The mere provision of
      laminar flow hood equipment in a physician's office is insufficient without a
      consistent policy for nursing personnel to follow. Such a policy should be
      established through the development of a standardized manual appropriate for the
      office that includes procedures required for the equipment. Adapting safety
      guidelines into an office procedural manual provides a practical and consistent
      approach to enhancing personal safety for oncology nurses within community office
      settings. IMPLICATIONS FOR NURSING PRACTICE: With today's rapid expansion of
      ambulatory chemotherapy services, the need for specialized instruction in the
      safe handling of cytotoxic drugs has become increasingly apparent. In the course
      of their duties, private office oncology nurses endure daily exposure to toxic
      agents, which poses a concern for occupational safety. An established procedure
      manual standardizes safe work practices for use in training new personnel and
      evaluating staff exposure to cytotoxic drugs.

PMID- 9010865
TI  - If only you do it well. Autobiography.

PMID- 9010866
TI  - Apoptosis in ocular disease: a molecular overview.
AB  - Apoptosis is a form of genetically programmed cell death that can be induced by a
      variety of different stimuli. It is often referred to as a form of cellular
      suicide. Typically, apoptosis is characterized by the condensation and shrinkage
      of the cellular nucleus and cytoplasm, followed by the complete fragmentation of
      the cell and subsequent phagocytosis of the debris by surrounding cells. Although
      important during development, and also for maintaining homeostasis in some adult
      tissues, apoptosis can also be associated with disease processes. Recent
      laboratory studies indicate that apoptosis is a mechanism of cell death in
      several important ocular diseases including glaucoma, retinitis pigmentosa,
      cataract formation, retinoblastoma, retinal ischemia, and diabetic retinopathy.
      This review summarizes the results of these studies and provides a brief
      description of some of the key molecules that are involved in the genetic
      regulation of apoptosis. It is possible that a complete understanding of how
      these molecules function may someday lead to new treatment options aimed at
      blocking the death of cells in a variety of ocular diseases.

PMID- 9010868
TI  - Full characterization of the maculopathy associated with an Arg-172-Trp mutation
      in the RDS/peripherin gene.
AB  - The objective of this study was to fully characterize the macular dystrophy
      phenotype and genotype in a large family of the Zermatt area of Switzerland.
      Clinical and molecular studies of the family included a comprehensive eye
      examination and a mutational analysis of the RDS, rhodopsin, and TIMP-3 genes. In
      selected cases, fluorescein angiography, perimetry, and electroretinography were
      performed. Forty-two family members at risk of expressing the maculopathy were
      studied. Of these, 24 were found to be clinically affected. The severity of
      macular disease in these patients was clearly age-related and different stages of
      progression were identified. Central pigmentary alterations were seen in
      adolescent patients, while patients in their late teens and twenties exhibited
      drusen-like deposits. Later, these defects formed focal areas of atrophy which
      eventually led to central geographic atrophy with severe visual loss by the fifth
      decade and cone-rod dysfunction. The transmission of this condition is autosomal
      dominant with complete penetrance. The underlying genetic defect is a mutation in
      codon 172 of the RDS/peripherin gene, a gene expressed in both rods and cones,
      which results in the substitution of tryptophan for an arginine residue at that
      position. 'Zermatt macular dystrophy' is a dominant, age-related, progressive
      macular dystrophy which in later stages resembles atrophic age-related macular
      degeneration. The size of the family studied allowed definition of the clinical
      spectrum of this condition and identification of the related genetic defect which
      allows more precise diagnosis and counseling.

PMID- 9010867
TI  - Pigmented ocular fundus lesions and APC mutations in familial adenomatous
      polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) results from a germline mutation
      in the adenomatous polyposis coli (APC) gene on chromosome 5q21. The extracolonic
      manifestations of FAP include pigmented ocular fundus lesions (POFLS), cutaneous
      cysts, osteomas, occult radio-opaque jaw lesions, odontomas, desmoids, and
      extracolonic cancers. POFLS are present at birth in about 80% of patients with
      FAP and are excellent clinical congenital markers for the disease. We studied the
      distribution of POFLS by number and APC mutation in families of the Johns Hopkins
      Polyposis Registry. MATERIALS AND METHODS: Of the 51 families with FAP, 42 (82%)
      had an identifiable APC mutation. We correlated the presence/absence and
      distribution by number of POFLS with the type and location of the mutation in the
      APC gene in 21 families where an ocular examination had been performed in at
      least one affected member, and where a systematic search for mutations in the APC
      gene had been undertaken. Families were considered POFL-positive if the average
      number of lesions per patient was three or more, or if at least one family member
      had three or more lesions. RESULTS: Fifteen of the 21 families (71.4%) were POFL
      positive. Mutations of the APC gene were detected in 15 of the 21 families. Of
      these, 12 (80%) were POFL-positive. Families with mutations at condons 215 (exon
      5) and 302 (exon 8) were POFL-negative. Families with mutations at condons 541,
      625, 1055, 1059, 1061, 1230, 1309, 1465, and 1546 (exons 12-15) were POFL
      positive. One patient with a mutation at codon 2621 (exon 15) had no POFLS.
      CONCLUSIONS: Mutations in exons 1-8 and the distal portion of exon 15 of the APC
      gene are associated with a POFL-negative phenotype, while those in exons 10 to
      the proximal portion of exon I5 are generally associated with a POFL-positive

PMID- 9010869
TI  - Two novel mutations in the Norrie disease gene associated with the classical
      ocular phenotype.
AB  - Norrie disease (ND) is a rare X-linked recessive disorder characterized by
      congenital blindness due to a degenerative and proliferative dysplasia of the
      neuroretina and, occasionally, by deafness and mental handicap. Here, we report
      two novel mutations detected in patients with the classical eye features of ND.
      Both the one-base pair insertion in exon II (544/545 insA) and the two-base pair
      deletion in the start codon (418delTG) of the ND gene predict a functional 'null
      allele', i.e. the complete absence of the corresponding gene product.

PMID- 9010870
TI  - Novel rhodopsin mutation (M216R) in a Danish family with autosomal dominant
      retinitis pigmentosa.
AB  - A novel rhodopsin missense mutation (M216R) was found in a Danish patient with
      autosomal dominant retinitis pigmentosa. Clinical examination of the proband
      disclosed a phenotype of intermediate severity. In view of the predicted amino
      acid substitution in the 5th transmembrane domain of rhodopsin, the clinical
      picture of the proband is in keeping with the data from the literature on
      patients carrying similar mutations.

PMID- 9010871
TI  - The 'GIST' score: ranking glaucoma for genetic studies. Glaucoma Inheritance
      Study of Tasmania.
AB  - The 'GIST' score was developed to facilitate linkage analysis of adult-onset
      primary open angle glaucoma (POAG) pedigrees in the Glaucoma Inheritance Study of
      Tasmania (GIST). Previous genetic linkage studies on juvenile open angle glaucoma
      pedigrees have relied upon an analysis of definitely affected individuals using
      the 'single best diagnosis' convention. Studies of adult-onset POAG have been
      complicated by limited numbers of unequivocally affected members identified even
      in very large pedigrees due to the later onset of the disease. Many members of
      the pedigree may have equivocal clinical features or are too young to show signs
      of the disease. The 'GIST score' is a numeric value between zero and one where
      zero is clinical certainty of absence of the disease and one is the definitive
      diagnosis of POAG. The score is developed by assigning relative weighting to key
      clinical features which results in a 'pedigee probability' of the diagnosis being
      present or absent in a member of a pedigree. Ranking of borderline and unaffected
      glaucoma subjects allows the laboratory more flexibility in the use of the
      members of the pedigree for linkage analysis. The score is not intended to have
      clinical usefulness in management of glaucoma.

PMID- 9010872
TI  - The problem of overlapping glaucoma families in the Glaucoma Inheritance Study in
      Tasmania (GIST).
AB  - The Glaucoma Inheritance Study in Tasmania (GIST) is a population survey of
      Australia's island state, Tasmania (population 450,000). Its aim is to find
      families with autosomal dominant, adult-onset, primary open angle glaucoma (POAG)
      suitable for genetic linkage analysis. POAG is relatively common, affecting
      around 3% of the Australian population. By finding the large families with POAG
      and identifying all the descendants in a captive population, it is possible that
      there may be overlap of different glaucoma pedigrees. Three of the first thirteen
      families in the study were composed of overlapping pedigrees. In one GIST family,
      GTas3, there has been intermarriage with other pedigrees with glaucoma on five
      occasions. The possibility of multiple genotypes was also reinforced by the
      inability to determine a single glaucoma phenotype in this family. When finding
      large families of POAG for linkage analysis, researchers must be aware of the
      risk of affected individuals inheriting their gene from the alternate parent.
      Thus, the alternate parents or their families must be examined, especially if the
      phenotype is atypical for the rest of the family.

PMID- 9010873
TI  - Coats' disease and central nervous system venous malformation.
AB  - Primary retinal telangiectasis or Coats' disease is a non-hereditary retinal
      vascular abnormality consisting of incompetent telangiectatic and aneurysmal
      retinal vessels. It is characteristically found unilaterally in boys and
      occasionally may be associated with other systemic disorders. The authors report
      the first case of primary retinal telangiectasis with a concomitant diffuse
      central nervous system venous abnormality.

PMID- 9010874
TI  - Mechanical behavior and biochemical composition of canine knee cartilage
      following periods of joint disuse and disuse with remobilization.
AB  - The mechanical behavior and biochemical composition of articular cartilage were
      studied in an experimental model of joint disuse, in which the canine knee was
      immobilized in a sling at 90 degrees of flexion. Articular cartilage from the
      surface zone of the femur was tested in an isometric tensile test and full
      thickness cartilage on the tibial plateau was tested in a compressive indentation
      test. Water, proteoglycan and collagen contents were measured in site-matched
      samples. Site-specific increases in the tensile moduli (approximately 88% above
      control values in distal femoral groove) were observed in cartilage after 8 weeks
      of joint disuse, and after 3 weeks of remobilization following either 4
      (approximately 140%, distal and proximal femoral groove) or 8 weeks
      (approximately 140%, distal femoral groove) of joint disuse. In contrast, the
      compressive properties of cartilage determined in the indentation test exhibited
      no change from control values with joint disuse or disuse followed by
      remobilization. Water contents increased at some sites on the tibia after 8 weeks
      of joint disuse (approximately 6% of tissue wet weight, posterior site), but not
      in the surface zone tissue of the femur. Proteoglycan/collagen and cartilage
      thickness were not found to change with disuse or disuse followed by
      remobilization. Reduced values for the ratio of proteoglycan:water were observed
      in the surface zone tissue of the femur (approximately 23%, distal femoral
      groove) and in the full-thickness tissue of the tibia (approximately 21%,
      anterior and posterior sites) after periods of joint disuse. In this study, the
      measured material properties suggest that the articular surface remains intact
      following periods of disuse or disuse with remobilization. This finding suggests
      one important difference between this model of joint disuse and other
      experimental models in which cartilage changes are both progressive and
      degenerative, such as surgically-induced joint instability.

PMID- 9010875
TI  - The effects of position on the radiographic joint space in osteoarthritis of the
      hip.
AB  - The aim of the study was to assess whether radiographic hip joint space thickness
      was changed by weight-bearing (WB) compared with non weight-bearing (NWB)
      position, and to evaluate whether radiographs centered on the hip were more
      sensitive than pelvic X-rays to detect such a change. Anteroposterior radiographs
      of the pelvis were made in 30 patients with hip osteoarthritis OA (46 OA and 11
      normal hips). Osteoarthritic, as well as contralateral normal hips were analyzed.
      Radiographs centered on OA hip were performed in 28 other patients. X-rays were
      made in WB and NWB positions using a standardized radiological procedure.
      Measurements of mean joint space width (MeanJSW) maximum joint space narrowing
      (MaxJSN) and joint space surface area (JSA), were made using a computerized image
      analysis system. The joint space width was unaffected by WB in normal joints but
      decreased with WB in OA joints. The decrease was significant only when
      considering MaxJSN in patients with a joint space thickness smaller than 2.5mm.
      The difference between WB and NWB was larger in radiographs centered on the hip
      than on pelvic X-rays. MeanJSW and JSA were found to be less sensitive than
      MaxJSN. The decrease of joint space width was inversely correlated with joint
      space size in WB. These results suggest that WB radiographs of the hip should be
      used in preference to NWB in studies of hip OA.

PMID- 9010876
TI  - Prevalence of degenerative morphological changes in the joints of the lower
      extremity.
AB  - Information on the prevalence and extent of degenerative morphological changes
      (DMC) in the joints of the lower extremity, including foot joints is sparse. In
      the present study, the first and fifth metatarsalphalangeal (MTP), transverse
      tarsal, subtalar, talocrural, knee and hip joints of 50 cadavers were examined
      grossly and graded on a five-point scale for signs of DMC. Selected samples were
      examined histologically. Our results confirm clinical findings that severe DMC in
      foot joints are uncommon except in the first MTP joint where the plantar aspect
      is most affected. The knee joint displayed the most numerous and severe signs of
      DMC followed by the first MTP joint. The hip, talocrural, subtalar and transverse
      tarsal joints displayed comparatively moderate levels of DMC while the fifth MTP
      was rarely affected. The only joint to display significantly greater levels of
      DMC on the distal side of the joint as compared with the proximal side, when a
      difference was present, was the hip. There were significantly greater levels of
      DMC on the medial aspect of two or more joints within an extremity than on the
      lateral aspect. Radiographs often showed few or no signs of DMC even when erosion
      down to subchondral bone was observed upon gross examination.

PMID- 9010877
TI  - Axial lower-limb alignment: comparison of knee geometry in normal volunteers and
      osteoarthritis patients.
AB  - Osteoarthritis of the knee is associated with deformities of the lower limb and
      malalignment of the limb segments. Pathogenetic relationships between the two are
      poorly understood. Alignment was studied by standardized radiography in 167
      symptomatic Canadian osteoarthritis patients, and compared with 119 healthy adult
      volunteers. In healthy adults overall alignment (hip-knee-ankle angle) was
      principally determined by distal femoral valgus (condylar hip angle) and proximal
      tibial-plateau varus (plateau-ankle angle): the angle between the joint surfaces
      (condylar plateau) was relatively constant. In osteoarthritis, disease-associated
      differences included condylar-plateau angles that were divergent: accentuated
      medial convergence in varus osteoarthritis and lateral convergence in valgus
      osteoarthritis. This was interpreted as change arising from focal loss of
      cartilage in the medial (varus osteoarthritis) or lateral (valgus osteoarthritis)
      compartments of the knee. The changes would contribute to increasing limb
      malalignment during disease progression. But differences of limb geometry also
      contributed to malalignment. These were the average trends: in varus
      osteoarthritis there was abnormal femoral geometry (lesser femoral condylar
      valgus), but tibial surface geometry was the same. In valgus osteoarthritis, the
      opposite was true: abnormal tibial geometry (lesser plateau varus), but normal
      femoral geometry. A possible explanation is that these abnormal knee geometries
      pre-exist and predispose to osteoarthritis, although it is not impossible that
      they (like condylar-plateau angle) change as disease progresses. Further
      approaches to population studies are discussed based on these findings, along
      with their implications for knee surgery.

PMID- 9010878
TI  - Variation in proteoglycan metabolism by articular chondrocytes in different joint
      regions is determined by post-natal mechanical loading.
AB  - In this study we investigated the hypothesis that cartilage from defined regions
      of ovine stifle joints, which were subjected to differing mechanical stresses,
      contained phenotypically distinct chondrocyte populations. Chondrocyte phenotypes
      were identified by the relative biosynthesis of the proteoglycans (PGs) aggrecan,
      biglycan and decorin. Articular cartilage (AC) from adult and neonatal ovine
      stifle joints were examined. Cells were cultured as both full-depth AC explants
      and in alginate beads after their isolation from the AC matrix. When chondrocytes
      from the various topographical regions of adult ovine knee joints were cultured
      as explants they demonstrated a consistent difference with regard to the
      metabolism of aggrecan and decorin. Significantly, this topographically-dependent
      phenotypic expression of PGs was preserved when the chondrocytes were cultured in
      alginate beads. In adult joints, chondrocytes from the central region of the
      tibial plateau not covered by the meniscus, which is subjected to high mechanical
      loads in-vivo, synthesized less aggrecan but more decorin than cells from regions
      covered by the meniscus. When chondrocytes from identical AC regions of neonatal
      ovine joints were cultured as explants, no topographical difference in aggrecan
      nor decorin metabolism could be detected. The results of this study, in
      association with the existing literature, lead us to propose that post-natal
      mechanical loading of AC could select for chondrocyte clones or induce a lasting
      modulation of chondrocyte phenotypic expression in different joint regions. Such
      cellular changes could result in the synthesis of PG populations that confer
      properties to AC most suited to resist the variable mechanical stresses in the
      different joint regions. This study serves to emphasize the importance of using
      cartilage from identical joint areas when examining PG metabolism by
      chondrocytes. Further investigation into the relationship between mechanical
      loading, regional chondrocyte phenotype selection and the response of these cells
      to anabolic and catabolic factors may provide important insights into the focal
      nature of AC degeneration in osteoarthritis.

PMID- 9010879
TI  - Biochemical effects of estrogen on articular cartilage in ovariectomized sheep.
AB  - Cartilage is a sex-hormone-sensitive tissue but the role of estrogen in the
      pathogenesis of osteoarthritis (OA) remains controversial. In this study,
      intrinsic material properties and thickness of articular cartilage of the knee
      joint of ovariectomized (OVX) and estrogen-treated sheep were measured.
      Skeletally mature ewes (N = 36, same breed, same housing 4-5 years old) were
      divided into; sham treated (n = 9), OVX (N = 13), OVX plus one estradiol implant
      (OVXE; N = 10) and OVX plus two estradiol implants (OVX2E; N = 4). Twelve months
      following sham procedure or OVX, sheep were euthanized and articular cartilage
      from a total of 216 points in the left femorotibial (knee) joints was tested for
      aggregate modulus, Poisson's ratio, permeability, thickness and shear modulus
      (six sites per sheep). When all of the sites in each knee were grouped together,
      OVX had a significant effect on articular cartilage. The sham cartilage of all
      sites grouped together had a larger aggregate modulus (P = 0.001) and a larger
      shear modulus (P = 0.054) than the OVX tissue. No statistically significant
      differences were seen for permeability and thickness between OVX, sham, OVXE and
      OVX2E. Differences existed in biomechanical properties at the different sites
      that were tested. Overall, no one location tended to be lowest or highest for all
      variables. This biomechanical study suggests that OVX may have a detrimental
      effect on the intrinsic material properties of the articular cartilage of the
      knee, even though the cartilage of the OVX animals appeared normal. Treatment
      with estradiol implants ameliorated these deleterious effects and may have helped
      maintain the tissue's structural integrity. Our study supports epidemiological
      studies of OA in women after menopause. The protective effect of estrogen and
      it's therapeutic effect remain to be further defined. This model may allow the
      relationship of estrogen and estrogen antagonists to be studied in greater
      detail, and may be valuable for the study of the pathogenesis and therapies of OA
      of postmenopausal women, particularly in its early stages.

PMID- 9010880
TI  - Preliminary report: increased porosity of the subchondral plate in an accelerated
      canine model of osteoarthritis.

PMID- 9010881
TI  - Saliva as a specimen for therapeutic drug monitoring in pharmacies.

PMID- 9010882
TI  - Developments in antithrombotic therapy: state of the art anno 1996.
AB  - This review aims to discuss recent developments in antithrombotic therapy. New
      and specific inhibitors of platelet dependent thrombosis appear to moderately
      improve the outcome in coronary vascular disease. Further studies will need to
      address the cost-benefit ratio of this additional intervention. Hirudin and
      analogues are potent inhibitors of thrombin, and are clinically efficious, but at
      current dosage levels still complicated by bleeding. Low molecular weight heparin
      have markedly improved the efficacy of prevention and treatment of venous
      thromboembolism.

PMID- 9010883
TI  - ACE inhibitors and proteinuria.
AB  - This review discusses the clinical consequences of urinary protein loss and the
      effects of inhibitors of the angiotensin converting enzyme (ACE) on this clinical
      finding. Proteinuria appears to be an important risk factor for renal function
      deterioration and for cardiovascular mortality. ACE inhibitors have been shown to
      reduce proteinuria more effectively than other antihypertensives. Their
      antiproteinuric effect seems to be independent of the underlying renal disease,
      and is mediated by a specific, not yet fully elucidated mechanism. Urinary
      protein loss related phenomena, such as hypoalbuminemia and aberrant lipoprotein
      profile, tend to improve also during ACE inhibitor treatment. Furthermore, ACE
      inhibition has been shown to prevent the renal function deterioration that is
      frequently observed in patients with renal disease. Interestingly, it has
      recently been shown that in proteinuric patients with renal disease the initial
      proteinuria lowering response to ACE inhibition predicts long-term renal function
      outcome during this treatment the more proteinuna is lowered during the first
      months, the better renal function will be preserved over the following years.
      Because of these favorable effects ACE inhibitors have become a widely used class
      of agents in nephrology. They are not only prescribed for lowering blood pressure
      in the hypertensive renal patient, but also as symptomatic treatment of patients
      with proteinuria, and to prevent renal function loss in patients with both
      diabetic and non-diabetic renal disease.

PMID- 9010884
TI  - Time-dependent variability of chloroquine secretion into human saliva.
AB  - Chloroquine has been reported to be secreted into human saliva. This is a report
      of a study designed to underscore the importance of the finding. It involved the
      administration of 600 mg chloroquine per oral to seven volunteers and 150 mg by
      intramuscular route to six others. Blood and simultaneous saliva samples were
      collected and analyzed for the drug by an HPLC method. The results showed that
      chloroquine reaches peak concentration at the same time in both plasma and saliva
      after oral administration of the drug. A good correlation was obtained between
      the AUC values derived from saliva and plasma level data. Saliva to plasma
      concentration ratios obtained after administration of the drug by both routes
      were high (mean > 11) and exhibited a time-dependent variability. These results
      suggest that an active process, among other mechanisms, may be involved in the
      transfer of chloroquine into human saliva. Caution should be exercised in the use
      of saliva for therapeutic monitoring of chloroquine.

PMID- 9010885
TI  - The quality of the professional practice of community pharmacists: what can still
      be improved in Europe?
AB  - This article describes a research project concerning the professional practice of
      community pharmacists in Western Europe. In 1990 interviews were held with key
      figures and practising pharmacists in the Netherlands, Belgium, Great Britain,
      Sweden and Portugal. In 1991 a questionnaire was sent which was answered by 929
      pharmacists. Concerning the quality of the professional practice it appeared that
      pharmacists have integrated certain structure aspects such as the use of a
      computer or a separate patient consultation room to varying degrees. Also
      concerning process aspects with regard to quality, for example the degree to
      which attention is given to counter work and prescription controls, there are
      large differences between pharmacists from the different countries. These
      differences between pharmacists appeared to depend upon differences in legal
      rules (such as the compulsory presence of a pharmacist in Belgium, Sweden and
      Portugal or the compulsory prescription control by a pharmacist before delivery
      in Great Britain), financial and economic circumstances, internal organizational
      characteristics of the pharmacy and the individual personal task conceptions of
      the pharmacist. New developments, for example in areas of patient information and
      computer use, seem to be followed most in the Netherlands and Sweden. General
      statements about differences in quality are not easily made because the community
      pharmacy in other countries also has certain positive aspects, such as being
      easily accessible (Portugal), personal involvement of the pharmacist (Belgium)
      and personal control by the pharmacist (Great Britain). Looking at the diversity
      within Europe the conclusion can be reached that the European pharmacist' does
      not yet exist.

PMID- 9010886
TI  - Initiation of clinical pharmacy in Greece.
AB  - INTRO: There was neither Clinical Pharmacy practice in Greece nor Hospital
      Formularies. Clinical Pharmacy (CP) services started experimentally during a 3
      month period (February 1995-April 1995) at the 2nd surgical Department of
      "Apostle Paul-KAT" Hospital in Athens. Since then there has been a strategy plan
      for further CP development. Our aim is to give information about these first
      steps in introducing CP in Greece. METHOD: The work at the Department was based
      on the prescription monitoring of every patient, realizing the prescribing trends
      and giving priority to certain prescribing problems. Eventually there was a focus
      on antibiotics and respiratory system drugs. RESULTS: 250 patients 91
      interventions for alternative drug treatment and the duration of antibiotic
      treatment 25 interventions for individualization of drug dosage. 15 cases of
      monitoring adverse effects. 12 discussions with patients consulting them about
      their drug treatment 4 educational presentations. High acceptance by the medical
      staff. Comparison of 2 months (pre and post CP services) revealed 50.7% reduction
      in antibiotics and respiratory system drugs. Total cost saving 1,034120 drs-->E
      2,787 for one month. CONCLUSIONS: The results of the 1st experimental 3-month
      period are indicative for the consequences of CP services both for the quality of
      pharmaceutical care and pharmaco-economics. Implementation of CP services by
      organizing a CP dept or Unit will influence the pharmaceutical policy of the
      Hospital and lead to institutional changes, such as a Hospital Formulary.

PMID- 9010888
TI  - Pharmaceutical care in The Netherlands. History, definition and projects.
AB  - The evolving concept of Pharmaceutical Care knows different interpretations in
      different countries. In the Netherlands community pharmacists already perform
      several functions which may be part of the Pharmaceutical Care concept. The Dutch
      concept of Pharmaceutical Care is tested in the TOM and OMA-projects. Patients
      recognise the educational, aspects of Pharmaceutical Care and in general are
      content about the provision thereof.

PMID- 9010889
TI  - The Electronic Pharmaceutical Dossier: an effective aid to documenting
      pharmaceutical care data.
AB  - Pharmaceutical care involves decision-making based upon communication and
      judgements to avoid, initiate maintain or discontinue pharmacotherapy. After
      establishing patient-pharmacist relationships and implementing collaboration with
      physicians based upon consensus guidelines, relevant information should be
      collected and processed in order to determine drug therapy problems and desired
      treatment outcomes. This paper describes in short the development of a 'care
      concept' for pharmaceutical care and focuses in particular on the fully
      integrated functions of a pharmacy automation system (Pharmacom) for documenting
      relevant data and supporting the processing of drug therapy.

PMID- 9010887
TI  - Pharmaceutical care.
AB  - Drug-treatment failures can be prevented by applying a Pharmaceutical Care
      system. Therapeutic outcome monitoring is such a system, which can be applied to
      the (drug) treatment of several diseases like asthma, diabetes and cardiovascular
      diseases. Pharmaceutical Care is an outcome oriented, cooperative, systematic
      approach to providing drug therapy directed at the improvement of all dimensions
      of health related quality of life.

PMID- 9010890
TI  - The chronically ill patient and the pharmacist. Pharmaceutical care from the
      patient's perspective.
AB  - Dynamic changes in the world also affect the chronically ill patient. Relations
      with professionals are changing, including the relations with pharmacists.
      Patients expectations as described in this article, should be rewarded and then
      patients and pharmacist both will benefit.

PMID- 9010892
TI  - Predictors of tobacco sales to minors.
AB  - BACKGROUND: Our purpose was to determine which characteristics of buyers, stores,
      and store clerks predicted successful tobacco sales to minors. METHODS: Seventeen
      minors visited randomly selected retail outlets in the Austin, Texas, area and
      attempted to purchase tobacco products. We used logistic regression modeling to
      determine independent predictors of successful purchase attempts. RESULTS:
      Overall, 101 of 165 attempts (61.2%) were successful. Although legally required,
      only 25.3% of stores posted warning signs about underage purchase of tobacco, and
      stores with signs were no less likely to sell to minors than stores without
      signs. Successful attempts were more common from vendors in metropolitan
      locations and from vendors with no alcohol products. Only 8.1% of attempts
      succeeded when buyers were questioned (usually about age), compared with 95.6% of
      attempts when no questions were asked (P < 0.001). The best predictor of a
      successful purchase attempt was failure to question buyers (adjusted odds ratio =
      1,850; P < 0.001). CONCLUSIONS: Warning signs had no effect on vendors'
      compliance with the state minors' access law, and failure to question minors
      about their age substantially increased the odds of a successful purchase. Laws
      prohibiting tobacco sales to minors should be enforced by requiring vendors to
      obtain proof of buyers' ages for persons who appear to be < 30 years of age.

PMID- 9010891
TI  - Exposure of Puerto Rican children to environmental tobacco smoke.
AB  - BACKGROUND: Many studies of environmental tobacco smoke (ETS) have been conducted
      in northern, industrialized countries. As yet, however, no studies have been
      carried out on ETS exposure with nonsmokers living in tropical environments.
      METHODS: Urine specimens were collected from 175 healthy Puerto Rican children (2
      11 years) living in an industrial area and were analyzed for cotinine, a
      quantitative biomarker for exposure to ETS. Their parents completed a
      questionnaire covering smoking habits. RESULTS: Seventy percent of children were
      exposed to ETS. Quantitatively, exposure to smoke in households consuming more
      than 1 pack per day (ppd) caused a doubling of cotinine excretion compared with
      households consuming less than 1 ppd. Smoke from mothers made the greatest
      contribution to cotinine, followed by smoke from fathers, with smoke from other
      persons having no effect. Degree of exposure was inversely related to age of the
      child. CONCLUSIONS: Young children (2-4 years) were detected to have
      significantly greater exposure to ETS than older children (5-11 years) and in the
      younger group the effect seemed to be from the mother's smoking much more than
      the father's, with other persons contributing negligible amounts. This suggests
      an obvious strategy for prevention of exposure to ETS in young children.

PMID- 9010893
TI  - Are adolescents receptive to current sales promotion practices of the tobacco
      industry?
AB  - BACKGROUND: The tobacco industry increased the portion of its marketing budget
      for sales promotion to $2.5 billion in 1993. Although it claims not to target
      those under age 18 years, it is important to determine the extent to which
      adolescents are affected as participation may lead to smoking initiation.
      METHODS: California population surveys, conducted in 1993 among youth ages 12-17
      years (N = 5,531) and in 1994 among both youth (N = 1,735) and adults (N =
      4,170), asked questions regarding possession and willingness to use promotional
      items. RESULTS: In 1994, young adults (18-24 years) were the most likely to
      possess a promotional item (27.5 +/- 4.1, +/- 95% confidence limit). However,
      willingness to use an item was highest among those ages 15-17 years (35.4 +/-
      3.4%) and was also high among those ages 12-14 years (24.4 +/- 2.7%). Among
      youth, ownership or willingness to use promotional items was more likely for
      boys, whites, those reporting below average school performance, and those smoking
      or susceptible to smoking. Youth ownership of promotional items increased from
      1993 to 1994, as did the frequency of their obtaining items from coupons.
      CONCLUSIONS: Promotional marketing undertaken by the tobacco industry was
      effective in capturing the interest of adolescents, although actual acquisition
      was highest among young adults. The rapidly increasing interest in tobacco
      promotional items from 1993 to 1994 may soon translate into increased adolescent
      smoking rates.

PMID- 9010894
TI  - Smoking cessation rates 4 years after treatment by nicotine gum and acupuncture.
AB  - BACKGROUND: This study was done to estimate the smoking cessation rates 4 years
      after treatment with acupuncture and nicotine gum. METHODS: Participants were
      randomized in a 2 x 2 factorial design to four groups: double active treatments
      (nicotine gum and acupuncture), double placebo, and the combination of one active
      treatment and placebo. RESULTS: The success rates were quite similar in the four
      groups at the different points of follow-up. They sharply decreased between 1
      month (around 23%) and 1 year (around 10%). The decrease slowed down thereafter
      to around 6% at 4 years. CONCLUSIONS: Results from our study suggest that the two
      treatments did not offer any long-term improvement over placebo. Additional
      investigations are necessary to estimate the magnitude of their long-term success
      rate.

PMID- 9010895
TI  - Nutrition guidance by primary-care physicians: LISREL analysis improves
      understanding.
AB  - BACKGROUND: When determinants of nutrition guidance practices for primary care
      physicians (PCPs) are identified, the key question remains: what is the mechanism
      of action? This knowledge is essential in order to understand how PCPs practice
      nutrition guidance. METHODS: Mail questionnaires (result of focus-group
      discussions and in-depth interviews) were sent to a nationwide random sample of
      1,000 PCPs in the Netherlands, who had been in practice for between 5 and 15
      years (633 respondents). The mechanism of action of determinants of nutrition
      guidance practices of PCPs was identified by means of linear structural
      relationship analysis (LISREL) using a postulated model. RESULTS: The postulated
      model on the mechanism of action was confirmed. The model demonstrates that
      nutrition guidance practices of PCPs are directly and significantly based on a
      few predisposing factors; driving forces and perceived barriers may act as
      significant intermediary variables. The predisposing factors, driving forces, and
      perceived barriers were identified. CONCLUSION: Policies to improve nutrition
      guidance practices of PCPs may, in the future, benefit from a LISREL model
      analysis of determinants of these practices to become more effective. Using
      multiple regression analysis to ascertain the determinants of these practices
      could result in missing important predisposing factors and "hidden" intermediary
      factors and lead, therefore, to an incomplete understanding of the mechanism of
      action.

PMID- 9010896
TI  - Relative validity and repeatability of a new questionnaire on physical activity.
AB  - BACKGROUND: A physical activity questionnaire was developed with the aim to
      estimate usual individual daily energy expenditure. The questionnaire focused on
      the number of hours usually spent on various activities. In a pilot study it was
      tested for repeatability and validity in a population of 126 Dutch adults (64
      men, 62 women). METHODS: For assessment of repeatability the questionnaire was
      administered three times during the course of 1 year. A four-times-repeated 3-day
      activity diary was used as a reference instrument to evaluate validity. RESULTS:
      Differences in mean energy expenditure among repeated administrations of the
      questionnaire were small and not significant. Spearman's test-retest correlation
      coefficients for total energy expenditure for men were 0.76 [95% confidence
      interval (CI) 0.63-0.85] and 0.70 (95% CI 0.54-0.81) at 5 and 11 months,
      respectively, and for women were 0.58 (95% CI 0.36-0.74) and 0.71 (95% CI 0.54
      0.82). There was a significant trend showing increasing mean diary energy
      expenditure for successive tertiles of questionnaire energy expenditure. The
      correlation between the questionnaire and the diary was 0.66 (95% CI 0.49-0.78)
      for men and 0.43 (95% CI 0.18-0.63) for women. CONCLUSIONS: It was concluded that
      this questionnaire is a useful tool for estimating energy expenditure in
      epidemiological studies.

PMID- 9010897
TI  - Clinician compliance with primary prevention of tobacco use: the impact of social
      contingencies.
AB  - BACKGROUND: This study evaluated clinicians' compliance with delivering written
      advice and information against tobacco use (prevention prescriptions) to
      adolescent patients. METHODS: Clinicians in 77 orthodontic offices were trained
      (and asked) to provide anti-tobacco counseling and prescriptions to 10- to 18
      year-olds for 2 years. Each of eight prescriptions was provided for distribution
      to adolescent patients. Information concerning prescription-tracking methods and
      operant learning theory variables such as modeling and feedback was obtained
      using a cross-sectional interview of clinical staff. The proportion of
      prescriptions written was regressed on possible "determinants." Analyses were
      replicated for two time periods. RESULTS: Mean anti-tobacco prescription
      compliance was 66 and 73% for two separate time periods. Multiple regression
      analyses were computed for the first (R = 0.45, F(7,63) = 2.29, P < 0.001) and
      second (R = 0.48, F(7,63) = 2.76, P < 0.001) time periods. Prescription tracking
      and praise from patients were significant correlates for the first time period;
      praise and modeling were significant for the second time period. Twenty and
      twenty-three percent, respectively, of the variance in office prescription rate
      was explained. CONCLUSIONS: Results suggest that compliance with primary
      prevention procedures may be influenced by feedback from patients, staff
      modeling, and formal office tracking information.

PMID- 9010898
TI  - Multivariate profile of smoking in Southeast Asian men: a biochemically verified
      analysis.
AB  - BACKGROUND: Cigarette smoking prevalence rates among Southeast Asian males are
      among the highest reported in comparison with other ethnic male groups in the
      United States. The objective of this study is to profile current smokers, former
      smokers, and never smokers among Southeast Asian males, based on subject
      characteristics. METHODS: Southeast Asian (Cambodian, Laotian, and Vietnamese)
      males residing in the Greater Columbus, Ohio, area were surveyed, utilizing
      culturally sensitive instruments and interviewers, with respect to demographic
      and acculturation variables. All subjects were biochemically verified by
      collecting a saliva sample at the time of the interviews. RESULTS: Those
      Southeast Asian males who quit smoking tended to be older, employed, more
      assimilated into the U.S. culture, and of Cambodian ethnicity. The current
      smokers, relative to never smokers, tended to be older, not in the labor force,
      traditionally oriented to their native culture, less educated, and of Laotian or
      Vietnamese ethnicity. CONCLUSIONS: Specific strategies for smoking cessation
      programs would indicate more intense, and possibly different, efforts be directed
      at Southeast Asian males of Laotian and Vietnamese ethnicity who are younger,
      unemployed and less assimilated into the U.S. culture. On the other hand, smoking
      prevention programs would target those individuals who are at highest risk of
      smoking.

PMID- 9010899
TI  - Assessment of preventive health care: design considerations.
AB  - OBJECTIVE: To design an instrument to assess the performance of a clinic in the
      delivery of preventive health services to a general population. METHODS: The
      study utilized a chart review of services delivered, abstraction of data from
      electronic databases, and a standardized provider assessment of each eligible
      patient. The study was conducted in a primary care clinic staffed primarily by
      internal medicine residents in an urban academic medical center. Patients who
      were receiving continuity care in the clinic and who were scheduled for an
      appointment during the 2-week study period were eligible for inclusion. Patients
      were identified prospectively from the appointment schedule. Charts were reviewed
      for the delivery of preventive health services prior to the patient's visit.
      Assessment forms were provided to the primary providers for review and
      completion. Demographic and appointment information was electronically abstracted
      from current databases. RESULTS: The rate at which services were provided varied
      considerably by service and over time. The reasons for nondelivery included
      disagreement with guidelines, patient resistance/refusal, and lack of priority.
      CONCLUSIONS: It should be possible to assess a clinic's performance over a range
      of services over its entire population over time. There may be legitimate reasons
      for services not being provided to a sizable proportion of the population. These
      issues are complex and require sensitive detailed investigation.

PMID- 9010901
TI  - A controlled trial of educational strategies to teach medical students brief
      intervention skills for alcohol problems.
AB  - OBJECTIVES: Comparatively little is known about the most effective educational
      strategies to train medical students to successfully intervene in their patients'
      alcohol problems. The relative effectiveness of two educational programs to teach
      medical students brief intervention skills for managing alcohol problems was
      examined. METHODS: Teaching took place over 3 hr and was either the traditional
      didactic teaching program on the principles and practice of brief and early
      intervention or an interactive program involving a shortened lecture, clinical
      practice, and small group feedback on clinical performance. Students were
      assessed on a 10-min videotaped encounter with a simulated patient before and
      after teaching according to how they addressed alcohol-related issues and on
      their general interactional skills. RESULTS: Performance on alcohol-related
      issues and interactional skills were significantly improved after teaching,
      although still poor in terms of clinical performance. A between-groups comparison
      on pre/ postteaching difference scores indicated interactive training was no more
      effective than traditional didactic lectures in developing the knowledge and
      skills needed for a brief alcohol intervention. CONCLUSION: The need for more
      detailed teaching sessions on sensitive areas such as alcohol use in indicated.

PMID- 9010900
TI  - Influenza vaccination of health care workers: evaluation of factors that are
      important in acceptance.
AB  - BACKGROUND: We evaluated the associations between putative occupational and
      epidemiologic determinants and influenza vaccine acceptance among health care
      workers during two consecutive seasons. METHODS: Multiple logistic regression
      models were developed to identify predictors of vaccine acceptance during 1991
      1992, then validated in the subsequent year. A combined repeated-measures
      regression model using generalized estimating equations was fit to examine
      workers' vaccine acceptance over the 2-year period. RESULTS: Nearly one-third of
      hospital employees received influenza vaccine each year [2,364 of 7,320 (32%) in
      1991-1992 vs 2,679 of 8,632 (31%) in 1992-1993]. Independent predictors among
      nurse clinicians included older age, higher salary, longer employment, and
      minimal absenteeism. Female sex, marriage, higher salary, and employment duration
      were independent predictors for professional support staff. Older age was the
      only independent predictor among nonprofessional staff. CONCLUSIONS: We conclude
      that older individuals, those with higher socioeconomic status, and those
      employed longer are more likely to accept the influenza vaccine. Sex, marital
      status, and prior work absenteeism are also important predictors in specific
      groups of health care workers.

PMID- 9010902
TI  - Prediction of peripheral fracture risk by quantitative microdensitometry.
AB  - BACKGROUND: The purpose of the study was to investigate whether quantitative
      microdensitometry (QMD) could be used for screening purposes to identify a
      population with a high risk for peripheral osteoporotic fractures. METHODS: In
      1984 bone mineral density (BMD) measurements were made on the index finger of 612
      women. Repeated BMD measurements were obtained in 1989 in 440 women. Cox
      proportional hazards models were used to obtain adjusted estimates of the hazard
      ratio of a fracture according to BMD or bone loss. Receiver operating
      characteristic curves were constructed and the areas under the curves (AUC) were
      compared. RESULTS: Thirty-five women experienced peripheral osteoporotic
      fractures between the first and the second measurement. Women in the three lowest
      quartiles of bone density were 1.4-1.8 times (diaphyseal site) and 2.4-2.8 times
      (metaphyseal site) as likely to experience a fracture as those in the highest
      quartile. Women in the quartile with the highest bone loss had a risk of 6.9
      (diaphyseal site) and 7.5 (metaphyseal site) times higher than women in the
      lowest quartile. The discriminative power of the measurement as a single test was
      moderate (AUC 63%); two successive measurements, made with an interval of 5 years
      to measure bone loss, increased the discriminating power (AUC 74%; P < 0.05).
      CONCLUSIONS: Phalangeal BMD and bone loss, as measured by QMD, are important risk
      factors for peripheral osteoporotic fractures, but cannot be used as an efficient
      screening instrument for selecting women with the highest fracture risk.

PMID- 9010903
TI  - A trial of church-based smoking cessation interventions for rural African
      Americans.
AB  - BACKGROUND: The Alliance of Black Churches Health Project was begun in an effort
      to address the health problems of the African-American residents of two rural
      Virginia counties. Smoking cessation was chosen as the principal target behavior
      in one county. Church coalitions were chosen as the principal organizations
      through which to implement the interventions. METHOD: A smoking cessation program
      was designed that combined one-on-one counseling with self-help materials and
      community-wide activities. To provide these services, up to two smoking cessation
      counselors were trained from participating churches. To evaluate the impact,
      population-based cohorts of smokers were assembled in each county using a door-to
      door survey. Respondents were recontacted after 18 months. Smoking cessation (1
      month continuous abstinence), stages of change, and exposure to the interventions
      were assessed. RESULTS: The overall smoking prevalence at baseline was 25.8%. At
      follow-up, the smoking cessation rate in the intervention county was 9.6% and in
      the control county 5.4% (P = 0.18). Among those attending church once a month or
      more, the respective quit rates were 10.5% and 5.9% (P = 0.20). There was
      significantly more progress along the stages of change in the intervention than
      in the control county. There was also higher awareness of and contact with
      smoking cessation programs in the former compared with the latter. CONCLUSION:
      Smoking cessation interventions for African Americans can be successfully
      implemented through a church coalition. The interventions were associated with
      significant progress along the stages of cessation. Although the quit rate was
      higher in the intervention community, the difference was not significant.

PMID- 9010905
TI  - Beliefs about dietary factors in breast cancer prevention among American women,
      1991 to 1995.
AB  - OBJECTIVE: To estimate the percentage of American women in various demographic
      groups who believe or have heard that dietary factors have a role in breast
      cancer prevention and to assess changes between 1991 and 1995. METHODS: Telephone
      surveys were conducted of random samples of 509 women in 1991 and 510 women in
      1995. Subjects were asked questions with increasing prompting to gauge their
      beliefs about the role of dietary factors in breast cancer prevention. RESULTS:
      The percentages of women citing dietary factors (reducing intake of fat or meat
      or increasing intake of vegetables, fruit, fiber, or vegetarian meals) as
      reducing the risk of developing breast cancer were 20% in 1991 and 23% in 1995.
      These numbers were lower among young, poor, and less educated women. When
      specifically prompted to consider dietary steps, the number citing such factors
      increased to 37% in 1991 and to 52% in 1995. CONCLUSION: The belief that there is
      a role for dietary factors in breast cancer is far from universal among American
      women, although some measures of the awareness of dietary factors increased
      significantly between 1991 and 1995. Women are more likely to cite mammography
      and breast self-examination as preventive steps, even though both are designed
      for detection rather than prevention. Additional efforts are needed to provide
      information on cancer prevention, particularly to young, poor, and less educated
      women, and to clarify the role of prevention as distinct from cancer detection.

PMID- 9010904
TI  - Community education programs to promote mammography participation in rural New
      York State.
AB  - BACKGROUND: Rural women are less likely to receive screening mammography at
      recommended intervals. This study evaluated efforts to promote screening
      mammography among women in rural communities through community education
      interventions and low-cost mobile mammography van services. METHODS: Two matched
      sets of communities were identified in an isolated rural region. One area
      received community education programs in addition to the mammography van for 2
      years; the second area received only the van services. The educational programs
      were designed using diagnostic research methods; they included recruitment of
      opinion leaders to organize small group breast screening education sessions, an
      information campaign using direct mail, and primary health care provider
      education. RESULTS: A household telephone survey conducted 6 months after
      completion of these programs indicated that mammography utilization and perceived
      mammography norms were higher among women in the Program area than among women in
      the Comparison area. Process data were consistent with these findings. Clinical
      examination and self-examination behaviors were not influenced by the programs.
      CONCLUSIONS: This study showed that well-focused educational interventions for
      rural women can increase utilization of screening mammography when access and
      cost barriers also are reduced.

PMID- 9010906
TI  - Sunbed use in Swedish urban adolescents related to behavioral characteristics.
AB  - BACKGROUND: Sunbed use among Swedish adolescents has not been extensively
      studied, nor has the social learning process associated with it. The purpose of
      this study was to explore Swedish adolescents' sunbed use in relation to sex,
      age, smoking, perceived physical attractiveness, attitudes to artificial and
      natural UV exposure, psychosomatic symptoms, and risk knowledge. METHODS: In the
      spring of 1993, 60 school classes comprising 1,502 students ages 14-19 were
      randomly selected to answer a questionnaire concerning sunbed use and sunbathing
      habits, smoking, perceived physical attractiveness, psychosomatic symptoms, and
      need for information about and knowledge of the risks of UV exposure. RESULTS: Of
      1,252 respondents, 57% had used sunbeds (females 70%, males 44%) > or = four
      times during the previous year. A marked increase (P < 0.001) in both sunbed use
      and smoking was detected between the 8th and the 9th grade (at ages 14-15).
      Sunbed use was also significantly correlated with sex, age, excessive tanning in
      natural sunlight, and low perceived physical attractiveness. The need for
      information on risks of high UV exposure was greatest among the best informed
      students and among students with high UV exposure (sunbed use, excessive tanning
      in natural sunlight). CONCLUSIONS: It seems doubtful whether further information
      on UV risks would result in altered behavior among highly exposed students, who
      seem receptive to information and have good knowledge. For a better understanding
      of the mechanisms underlying the association between sunbed use, smoking, and
      self-esteem, more in-depth, qualitative studies are required.

PMID- 9010907
TI  - Reducing maternal smoking and relapse: long-term evaluation of a pediatric
      intervention.
AB  - BACKGROUND: Pediatric well-care visits provide a clinical opportunity to counsel
      new mothers about their smoking and the deleterious effects of environmental
      tobacco smoke (ETS) on infant health. METHODS: Forty-nine Oregon pediatric
      offices enrolled 2,901 women who were currently smoking or had quit for
      pregnancy, using a brief survey at the newborn's first office visit. Randomly
      assigned offices provided advice and materials to mothers at each well-care visit
      during the first 6 months postpartum to promote quitting or relapse prevention.
      RESULTS: The intervention reduced smoking (5.9% vs 2.7%) and relapse (55% vs 45%)
      at 6-month follow-up, but logistic regression analysis at 12 months revealed no
      significant treatment effect. The intervention had a positive effect on secondary
      outcome variables, such as readiness to quit and attitude toward and knowledge of
      ETS. Multiple logistic regression analysis indicated that husband/partner smoking
      was the strongest predictor of maternal quitting or relapse. CONCLUSIONS: A
      pediatric office-based intervention can significantly affect smoking and relapse
      prevention for mothers of newborns, but the effect decreases with time.
      Consistent prompting of the provider to give brief advice and materials at well
      care visits could provide a low-cost intervention to reduce infant ETS exposure.

PMID- 9010908
TI  - Physical activity preferences, preferred sources of assistance, and perceived
      barriers to increased activity among physically inactive Australians.
AB  - BACKGROUND: Participation in regular moderate or vigorous physical activity
      substantially reduces risk for all-cause and cardiovascular-disease mortality and
      confers other health benefits. Efforts to decrease the population prevalence of
      inactivity will have a greater impact if they are tailored to the needs and
      preferences of the community. METHODS: In the Pilot Survey of the Fitness of
      Australians, a questionnaire was administered to a randomly selected sample of
      2,298 adults and included questions on the preferred sources of assistance or
      support to become physically active, preferred activities, and barriers to
      regular participation. The responses of those who were identified as
      insufficiently physically active (n = 1,232; 53.6%) were examined for men and
      women separately and for those aged 18 to 39, 40 to 59, and 60 to 78 years.
      RESULTS: The most-preferred activity was walking (38 and 68% of the youngest and
      oldest age groups, respectively). The most frequently cited barriers to more
      regular participation in the youngest age group were insufficient time, lack of
      motivation and child care responsibilities. Among those aged 60 to 78 years,
      injury or poor health were the most frequently cited barriers to activity. The
      most-preferred source of advice or assistance changed with age: more than 50% of
      the oldest age group wanted advice from a health professional (compared with 22%
      of the youngest group) and the opportunity to exercise with a group was the most
      preferred source of support for the youngest age group. CONCLUSIONS: The physical
      activity-related attributes of men and women and of younger and older age groups
      described in this study may be used to provide more relevant and appealing
      options for those who might otherwise be missed by "one-size-fits-all" physical
      activity promotion strategies.

PMID- 9010909
TI  - Smoking behavior and attitude toward smoking regulations and passive smoking in
      the workplace. A study among 974 employees in the German metal industry.
AB  - BACKGROUND: Smoking regulations at the workplace have been found to be acceptable
      and effective in many studies conducted in the United States. There is limited
      knowledge, however, on acceptance and effects of smoking regulations in European
      countries, particularly among blue collar employees. METHODS: We conducted a
      survey on smoking behaviour and attitude toward smoking regulations and passive
      smoking in a South German metal company. A self-administered questionnaire was
      mailed to 1,500 predominantly blue collar employees of whom 974 participated in
      the study (response rate 64.9%). RESULTS: About 30% of the employees were not
      allowed to smoke at their immediate work area. Among them, about 95% of both
      smokers and nonsmokers agreed with this smoking policy. More than 60% of
      nonsmoking blue collar workers were bothered by passive smoking at work whether
      or not smoking was allowed at their immediate work area. In contrast, the
      proportion of nonsmoking white collar employees who were bothered by passive
      smoking varied from 52% if smoking was allowed at their immediate work area to
      18% if smoking was not allowed. Prevalence of active smoking and average amount
      of smoking among active smokers were considerably lower among employees who were
      not allowed to smoke at work than among other employees. These differences were
      partly due to confounding by occupation, however, which was strongly related to
      both smoking habits and smoking policy. CONCLUSIONS: Our results, which confirm
      and extend previous findings, give further support to the acceptability and
      potential effectiveness of smoking regulations at the workplace. Particular
      efforts should be devoted to limit both active and passive smoking among blue
      collar employees.

PMID- 9010910
TI  - Risk factors for primary breast cancer in Japan: 8-year follow-up of atomic bomb
      survivors.
AB  - BACKGROUND: Findings from the Life Span Study (LSS) of the health effects of
      exposure to atomic bomb radiation have documented a strong dose-response relation
      between radiation exposure and breast cancer incidence. PURPOSE: We analyzed data
      from the LSS cohort to identify nonradiation risk factors for breast cancer and
      to determine whether these factors were independent of the effects of radiation
      on breast cancer occurrence. METHODS: Breast cancer incidence was ascertained
      among a cohort of 22,200 residents of Hiroshima and Nagasaki, Japan, who had
      completed a mail survey between 1979 and 1981 to study nonradiation risk factors
      for disease. During the subsequent follow-up period (average 8.31 years), 161
      cases of primary breast cancer were identified through population-based tumor
      registries in the two cities. RESULTS: The risk of breast cancer was inversely
      related to age at menarche and weakly positive in relation to age at menopause
      and years of menstruation. A significant negative association of full-term
      pregnancy against breast cancer was observed, although the number of pregnancies
      beyond the first was not related to the rate of breast cancer in the cohort.
      Women having their first full-term pregnancy before age 30 were at decreased risk
      of breast cancer relative to older women, but there was no trend. A
      nonsignificant, positive trend in risk was associated with increasing weight and
      body mass (kg/m2). The risk of breast cancer among women with a history of
      estrogen use was 1.64 (95% confidence interval 1.02-2.64) and with diabetes 2.06
      (95% confidence interval 1.27-3.34). It was not possible to distinguish among
      additive and multiplicative models of the joint association of radiation dose and
      various non-radiation-related exposures (age at menarche, full-term pregnancy,
      female hormone preparations) identified in this analysis. CONCLUSIONS:
      Nonradiation risk factors for breast cancer among Japanese atomic bomb survivors
      were consistent with those identified among other populations of women, although
      the prevalence of common risk factors was low. Reproductive factors and hormone
      use appear to act independently of radiation exposure on the risk of breast
      cancer among this population.

PMID- 9010911
TI  - Interaction between CD44 and osteopontin as a potential basis for metastasis
      formation.
AB  - Malignant growth has been associated with oncogene activation, telomerase
      activity, and expression of CD44 splice variants on the cell surface. Though
      dysregulation of growth control due to expression of oncogene products is fairly
      well understood, the mechanism of CD44-mediated homing and colony formation in
      specific tissues has remained cryptic. We have identified the cytokine
      osteopontin as a ligand for CD44. Osteopontin binds to naturally expressed and
      stably transfected CD44 in a manner that is specific, dose-dependent, inhibitable
      by anti-CD44 antibodies, insensitive to competition by Gly-Arg-Gly-Asp-Ser, and
      sensitive to competition by hyaluronate. The receptor-ligand interaction mediates
      chemotaxis or attachment, depending on presentation of osteopontin in soluble or
      immobilized form. In contrast, binding of CD44 to hyaluronate mediates
      aggregation or attachment but not chemotaxis. We found that two events occurring
      in malignancy-secretion of osteopontin and expression of CD44v-are linked in such
      a way that they may cause migration of tumor cells to specific sites of
      metastasis formation.

PMID- 9010912
TI  - Activation of the kallikrein-kinin system in arthritis and enterocolitis in
      genetically susceptible rats: modulation by a selective plasma kallikrein
      inhibitor.
AB  - We have developed models of acute and chronic inflammatory arthritis and
      enterocolitis using peptidoglycan-polysaccharide injected intraperitoneally or
      subserosally (intramurally) into the distal ileum and cecum. Acute inflammation
      occurs in both Buffalo and Lewis rats, characterized by inflammation of the
      injected areas of the intestine. However, only the genetically susceptible Lewis
      rat develops chronic synovitis and joint erosion or adhesions and granulomatous
      enterocolitis. In the Lewis rat but not the Buffalo rat, these changes are
      accompanied by a decrease in plasma prekallikrein and high-molecular-weight
      kininogen, reflecting activation of the kallikrein-kinin system. Pretreatment
      with a specific plasma kallikrein inhibitor modulates the acute and chronic
      arthritis. The same inhibitor partially abrogates the acute changes
      characteristic of enterocolitis, and preliminary data suggest similar results in
      the chronic model. The results of these studies indicate that the kallikrein
      kinin system plays an important role in arthritis and enterocolitis induced by
      bacterial products and that kallikrein inhibitors are potential therapeutic
      agents for inflammatory arthritis and inflammatory bowel disease.

PMID- 9010913
TI  - Antisense DNA toward type I protein kinase A produces sustained inhibition of
      tumor growth.
AB  - Expression of the RI alpha subunit of type I cyclic AMP-dependent protein kinase
      (PKA) is increased in human cancer cell lines, in primary tumors, in cells after
      transformation, and in cells upon stimulation of growth. The sequence-specific
      inhibition of RI alpha gene expression by RI alpha antisense oligodeoxynucleotide
      results in the differentiation of leukemia cells and growth arrest of cancer
      cells of epithelial origin. A single-injection RI alpha antisense treatment in
      vivo also results in a reduction in RI alpha expression and inhibition of tumor
      growth. One injection was sufficient to inhibit tumor growth in mice for 2 weeks.
      The antisense DNA achieves this long-lasting effect by altering the balance
      between the production of PKA type I and a competitive molecule, PKA type II.
      Tumor cells behaved like untransformed cells by making less protein kinase type
      I. The RI alpha antisense, which produces a biochemical imprint for growth
      control, requires infrequent dosing to restrain neoplastic growth in vivo.

PMID- 9010914
TI  - Abnormal formation of collagen cross-links in skin fibroblasts cultured from
      patients with Ehlers-Danlos syndrome type VI.
AB  - Ehlers-Danlos syndrome type VI (EDS VI) is an autosomal recessive disorder of
      connective tissue characterized by hyperextensible, friable skin and joint
      hypermobility. Severe scoliosis and ocular fragility are present in some
      patients. This disease is caused by defective collagen lsyl hydroxylase, a
      vitamin C-dependent enzyme that converts lysyl residues to hydroxylysine on
      procollagen peptides. Hydroxylysine is essential for the formation of the
      covalent pyridinium cross-links pyridinoline (Pyr) and deoxypyridinoline (Dpyr),
      among mature collagen molecules. Pyr derives from three hydroxylysyl residues,
      whereas Dpyr derives from one lysyl and two hydroxylysyl residues. Patients with
      EDS VI have high urinary excretion of Dpyr, resulting in a high ratio of Dpyr
      Pyr. In this study, we evaluate content and production of pyridinium cross-links
      in the skin and cultured fibroblasts from patients with EDS VI. The skin of
      normal controls contained both Pyr and Dpyr, with a marked predominance of Pyr as
      observed in normal urine. The skin of patients with EDS VI had reduced total
      content of pyridinium cross-links, with the presence of Dpyr but not Pyr. Long
      term cultures of control fibroblasts produced both Pyr and Dpyr, with a pattern
      resembling that of normal skin. By contrast, cross-links were not detected in
      dermal fibroblasts cultured from patients with EDS VI. Vitamin C, which improves
      the clinical manifestations of some patients with EDS VI, decreased Dpyr
      accumulation though only minimally affecting Pyr content in control cells. By
      contrast, addition of vitamin C to fibroblasts from patients with EDS VI
      stimulated the formation of Dpyr more than that of Pyr and greatly increased
      total pyridinium cross-link formation. These results indicate that qualitative
      and quantitative alterations of pyridinium cross-links occur in skin and in
      cultured dermal fibroblasts of patients with EDS VI and may be responsible for
      their abnormal skin findings. The vitamin C-stimulated production of Dpyr and Pyr
      in fibroblasts from patients with EDS VI may explain at least in part the
      therapeutic effects of this vitamin in EDS VI.

PMID- 9010915
TI  - Association of apoptosis of neutrophils and eosinophils and their ingestion by
      macrophages with resolution of the allergen-induced cutaneous late-phase response
      in atopic human subjects.
AB  - The allergen-induced cutaneous late-phase response serves as a model of allergic
      inflammation and is associated with infiltration of neutrophils, eosinophils, T
      cells, and macrophages. The mechanisms controlling the resolution of allergic
      inflammatory processes and the fate of infiltrating cells are uncertain. We
      observed that both the magnitude of the late-phase response and the numbers of
      infiltrating neutrophils and eosinophils peaked at 6 hr, persisted for 48 hr, but
      resolved completely by 7 days. In contrast, T-cell and macrophage numbers peaked
      between 24 and 72 hr after allergen challenge and persisted for up to 7 days. By
      using the techniques of terminal deoxynucleotidyl transferase-mediated biotin
      deoxyuridine 5'-triphosphate (dUTP) nickend-labeling (TUNEL) and by combining
      TUNEL with immunohistochemistry, we tested the hypothesis that the resolution of
      the late-phase response is associated with apoptosis of neutrophils and
      eosinophils, with subsequent engulfment of apoptotic cells and apoptotic bodies
      by tissue macrophages. As the cutaneous late-phase response resolved, there was a
      progressive increase (peaking at 72 hr) in the total numbers of TUNEL-positive
      (TUNEL+) cells and in the numbers of macrophages that had engulfed apoptotic
      cells and bodies. The majority of TUNEL+ cells were identified as neutrophils and
      eosinophils. In contrast, very little apoptosis was associated with T cells or
      macrophages. These experiments represent a novel demonstration of cell type
      specific apoptosis in vivo in human allergic inflammatory tissue and suggest that
      phagocytosis by macrophages of apoptotic neutrophils and eosinophils may be a
      mechanism that regulates resolution of the atopic allergic inflammatory response.

PMID- 9010916
TI  - Agmatine activation of nitric oxide synthase in endothelial cells.
AB  - Agmatine is a product of arginine decarboxylation. Systemic infusion of agmatine
      into rats causes hypotension. This effect could be due either to a central action
      of agmatine (a clonidine displacing substance), or to a direct effect of agmatine
      on cells of blood vessel walls, which induces them to cause vasodilatation, or
      both. In this study, we examined the effects of agmatine on endothelial cell
      function by using cultured bovine pulmonary artery endothelial cells. Agmatine
      stimulated nitrite production three-fold above basal nitrite formation by
      endothelial cells. The increased nitrite production by agmatine was inhibited by
      idazoxan but not by yohimbine. Agmatine displaced [3H]-idazoxan from endothelial
      cell membranes and was found to induce transients in the cytosolic calcium of
      endothelial cells. The transients could be downregulated by repeated exposure to
      agmatine but were not affected by pretreatment with norepinephrine. These results
      suggest that agmatine can bind to a cell surface imidazoline receptor on
      endothelial cells and can stimulate nitric oxide production by increasing
      cytosolic calcium. Therefore, agmatine appears to act directly on endothelial
      cells to increase the synthesis of nitric oxide, a vasodilatory substance.

PMID- 9010917
TI  - Identifying the hospitalized patient at risk for nosocomial bloodstream
      infection: a population-based study.
AB  - Included in a 3-year population-based study were all patients (n = 64,281)
      admitted to a single tertiary care hospital (902 beds) using prospective hospital
      wide surveillance for nosocomial infections. The objective of the study was to
      identify patients at risk for nosocomial bloodstream infection by using readily
      available hospital admission variables. After identifying potential risk factors
      for infection by univariate analyses, we derived multivariate models for
      predicting bloodstream infection by using logistical regression procedures. A
      total of 931 patients (1.45 per 100 admissions) developed a nosocomial
      bloodstream infection (2.2 episodes per 1000 patient-days) between 1 July 1987,
      and 30 June 1990. The crude mortality among infected patients was 34%, and the
      319 deaths represented 22% of the total in-hospital mortality. Independent
      predictors of bloodstream infection were age, gender, primary diagnosis, and
      admission to a critical care unit. The sensitivity and specificity of the models
      for classifying patients as infected or noninfected were 81% and 81% for infants
      (1-11 months old) and 72% and 72% for adults, respectively. The negative
      predictive value of both models exceeded 99%. Applied to all patients on
      admission, the models we developed allowed us to survey only 28% of patients to
      identify more than 70% of those who will develop a nosocomial bloodstream
      infection.

PMID- 9010918
TI  - Zinc deficiency: changes in cytokine production and T-cell subpopulations in
      patients with head and neck cancer and in noncancer subjects.
AB  - Cell-mediated immune dysfunctions and susceptibility to infections have been
      observed in zinc-deficient human subjects. In this study, we investigated the
      production of cytokines and characterized the T-cell subpopulations in three
      groups of mildly zinc-deficient subjects. These included head and neck cancer
      patients, healthy volunteers who were found to have a dietary deficiency of zinc,
      and healthy volunteers in whom we induced zinc deficiency experimentally by
      dietary means. We used cellular zinc criteria for the diagnosis of zinc
      deficiency. We assayed enzyme-linked immunosorbent assay the production of
      cytokines from phytohemagglutinin-stimulated peripheral blood mononuclear cells
      and assessed by flow cytometry the differences in T-cell subpopulations. Our
      studies showed that the cytokines produced by TH1 cells were particularly
      sensitive to zinc status, inasmuch as the production of interleukin-2 (IL-2) and
      interferon-gamma were decreased even though the deficiency of zinc was mild in
      our subjects. TH2 cytokines (IL-4, IL-5, and IL-6) were not affected by zinc
      deficiency. Natural killer cell lytic activity also was decreased in zinc
      deficient subjects. Recruitment of naive T cells (CD4+CD45 RA+) and CD8+ CD73+
      CD11b-, precursors of cytolytic T cells, were decreased in mildly zinc-deficient
      subjects. An imbalance between the functions of TH1 and TH2 cells and changes in
      T-cell subpopulations are most probably responsible for cell-mediated immune
      dysfunctions in zinc deficiency.

PMID- 9010919
TI  - Tyrosine kinase inhibitor-sensitive contractile action of ethanol in gastric
      smooth muscle: comparison with the action of epidermal growth factor.
AB  - We have evaluated the signal transduction pathways whereby, in comparison with
      epidermal growth factor-urogastrone, ethanol causes a rapid contractile response
      in guinea pig gastric longitudinal muscle. As for epidermal growth factor (EGF),
      the ethanol-induced contraction required extracellular calcium, was sensitive to
      the tyrosine kinase inhibitors genistein and tyrphostin 47 (AG213), and was
      blocked by both the cyclo-oxygenase inhibitor, indomethacin, and the
      diacylglycerol lipase inhibitor, U57908. The 50% effective concentration (EC50)
      for the contractile action of ethanol (approximately 140 mM) was lower than that
      for propanol and methanol and was not affected by the aldehyde dehydrogenase
      inhibitor, 4-methyl pyrazole. The actions of ethanol were distinct from those of
      EGF in that EGF-induced contractions were sensitive to the kinase C inhibitor
      GF109203X, and the EGF receptor kinase inhibitor PD153035, whereas ethanol
      induced contractions were refractory to these inhibitors. Further, EGF-induced
      contractions were attenuated by the voltage-sensitive calcium channel antagonist,
      nifedipine, whereas the ethanol-induced contractile response was resistant to
      nifedipine but blocked by the "receptor-operated" calcium channel antagonist
      SKF96365. We conclude that ethanol without metabolism via alcohol dehydrogenase
      causes a contractile response in gastric longitudinal muscle tissue via a
      tyrosine kinase inhibitor-sensitive signal pathway that is parallel in many
      respects but yet is distinct from that activated by EGF.

PMID- 9010920
TI  - Differential effects of subcutaneous GLP-1 on gastric emptying, antroduodenal
      motility, and pancreatic function in men.
AB  - In this study of eight healthy male volunteers, we investigated the effects of
      graded doses of subcutaneous glucagon like peptide-1(7-36)amide (GLP-1) on: 1)
      the gastric emptying pattern of a mixed liquid meal (300 kcal); 2) pancreatic
      enzyme secretion; 3) antroduodenal motility; and 4) the glycemic response as well
      as releases of insulin, C-peptide, and glucagon. GLP-1, 0.125 nmol/kg, or 0.25
      nmol/kg, or placebo was injected subcutaneously 5 min before meal ingestion.
      Subcutaneous GLP-1 dose-dependently prolonged the lag period (i.e., the time to
      reach maximal velocity of gastric emptying) by 46.2% (low dose) and 93.7% (high
      dose) (p < .05) but left unaltered maximal emptying velocity, total emptying
      time, and exponential emptying rate. With and without GLP-1, a fed motor pattern
      was induced by the meal and was terminated by an antral phase III when 98% of the
      meal had emptied. In parallel to the prolonged lag period, GLP-1 dose-dependently
      inhibited antral and duodenal motility and coordinated antroduodenal contractions
      by > 50% (low dose) and > 70% (high dose) (p < .05). GLP-1 initially reduced and
      thereafter transiently stimulated pancreatic enzyme secretion. This pattern
      correlated with the prolonged lag period and mirrored the delayed gastric
      emptying. GLP-1 retarded and diminished the postprandial glucose peak and reduced
      the total plasma glucose response by 46.6% (low dose) and by 59.4% (high dose) (p
      < .05). Both doses of GLP-1 delayed the postprandial insulin peak, enhanced total
      insulin release, and diminished postprandial responses of glucagon and pancreatic
      polypeptide. The duration of the lag period strongly correlated with the timing
      of postprandial glucose and insulin peaks (p < .001). The initial delay of
      gastric emptying, the enhancement of postprandial insulin release, and the
      inhibition of postprandial glucagon release were independent determinants (p <
      .01-.05) of the postprandial glucose response after subcutaneous administration
      of GLP-1.

PMID- 9010922
TI  - Crystal structure of glutathione synthetase at optimal pH: domain architecture
      and structural similarity with other proteins.
AB  - The crystal structure of Escherichia coli B glutathione synthetase (GSHase) has
      been determined at the optimal catalytic condition pH 7.5. The most significant
      structural difference from the structure at pH 6.0 is the movement of the central
      domain towards the N-terminal domain almost as a rigid body. As a result of this
      movement, new interdomain and intersubunit polar interactions are formed which
      stabilize the dimeric structure further. The structure of GSHase at optimal pH
      was compared with 294 other known protein structures in terms of the spatial
      arrangements of secondary structural elements. Three enzymes (D-alanine: D
      alanine ligase, succinyl-CoA synthetase and the biotin carboxylase subunit of
      acetyl-CoA carboxylase) were found to have structures similar to the ATP-binding
      site of GSHase, which extends across two domains. The ATP-binding sites in these
      four enzymes are composed of two antiparallel beta-sheets and are different from
      the classic mononucleotide-binding fold. Except for these proteins, no
      significant structural similarity was detected between GSHase and the other ATP
      binding proteins. A structural motif in the N-terminal domain of GSHase has been
      found to be similar to the NAD-binding fold. This structural motif is shared by a
      number of other proteins that bind various negatively charged molecules.

PMID- 9010921
TI  - Glutathione-independent prostaglandin D synthase as a lead molecule for designing
      new functional proteins.

PMID- 9010923
TI  - Pairwise iterative superposition of distantly related proteins and assessment of
      the significance of 3-D structural similarity.
AB  - A challenge lies in identifying distant protein 3-D structural similarity by
      rigid-body superposition. The most common measure of structural similarity is
      r.m.s. distance (r.m.s.d.) between topologically equivalent residues, and most
      automated methods of protein modelling rely on the assembly of rigid fragments
      from known 3-D structures. A fast method of improving the definition of a common
      protein fold by superposition, especially for distant relationships, is
      described. The definition of topological equivalence by the standard dynamic
      programming sequence alignment algorithm is extended by refining the entire
      structure alignment (not just those equivalenced residues within a given cut-off
      distance) and determining whether the alignment can be continued at the termini.
      The most appropriate distance-based definition of topological equivalence for a
      given comparison is identified. Despite the fact that hitherto the distant
      similarity between the globin fold and colicin A has not been recognized directly
      by rigid-body superposition, this new approach defines more equivalent residues
      with a lower r.m.s.d. between them than that obtained by the superposition of
      equivalences identified by a more elaborate method. A previous distance metric of
      3-D structural similarity derived from rigid-body superposition has been extended
      to the assessment of superpositions where topological equivalences have been
      determined by methods other than rigid-body ones.

PMID- 9010924
TI  - Detection of non-topological motifs in protein structures.
AB  - We present an efficient technique for the comparison of protein structures. The
      algorithm uses a vector representation of the secondary structure elements and
      searches for spatial configurations of secondary structure elements in proteins.
      In such recurring protein folds, the order of the secondary structure elements in
      the protein chains is disregarded. The method is based on the geometric hashing
      paradigm and implements approaches originating in computer vision. It represents
      and matches the secondary structure element vectors in a 3-D translation and
      rotation invariant manner. The matching of a pair of proteins takes on average
      under 3 s on a Silicon Graphics Indigo2 workstation, allowing extensive all
      against-all comparisons of the data set of non-redundant protein structures. Here
      we have carried out such a comparison for a data set of over 500 protein
      molecules. The detection of recurring topological and non-topological, secondary
      structure element order-independent protein folds may provide further insight
      into evolution. Moreover, as these recurring folding units are likely to be
      conformationally favourable, the availability of a data set of such topological
      motifs can serve as a rich input for threading routines. Below, we describe this
      rapid technique and the results it has obtained. While some of the obtained
      matches conserve the order of the secondary structure elements, others are
      entirely order independent. As an example, we focus on the results obtained for
      Che Y, a signal transduction protein, and on the profilin-beta-actin complex. The
      Che Y molecule is composed of a five-stranded, parallel beta-sheet flanked by
      five helices. Here we show its similarity with the Escherichia coli elongation
      factor, with L-arabinose binding protein, with haloalkane dehalogenase and with
      adenylate kinase. The profilin-beta-actin contains an antiparallel beta-pleated
      sheet with alpha-helical termini. Its similarities to lipase, fructose
      disphosphatase and beta-lactamase are displayed.

PMID- 9010925
TI  - Hydrophobic regions on protein surfaces: definition based on hydration shell
      structure and a quick method for their computation.
AB  - The hydrophobic part of the solvent-accessible surface of a typical monomeric
      globular protein consists of a single, large interconnected region formed from
      faces of apolar atoms and constituting approximately 60% of the solvent
      accessible surface area. Therefore, the direct delineation of the hydrophobic
      surface patches on an atom-wise basis is impossible. Experimental data indicate
      that, in a two-state hydration model, a protein can be considered to be unified
      with its first hydration shell in its interaction with bulk water. We show that,
      if the surface area occupied by water molecules bound at polar protein atoms as
      generated by AUTOSOL is removed, only about two-thirds of the hydrophobic part of
      the protein surface remains accessible to bulk solvent. Moreover, the
      organization of the hydrophobic part of the solvent-accessible surface
      experiences a drastic change, such that the single interconnected hydrophobic
      region disintegrates into many smaller patches, i.e. the physical definition of a
      hydrophobic surface region as unoccupied by first hydration shell water molecules
      can distinguish between hydrophobic surface clusters and small interconnecting
      channels. It is these remaining hydrophobic surface pieces that probably play an
      important role in intra- and intermolecular recognition processes such as ligand
      binding, protein folding and protein-protein association in solution conditions.
      These observations have led to the development of an accurate and quick
      analytical technique for the automatic determination of hydrophobic surface
      patches of proteins. This technique is not aggravated by the limiting assumptions
      of the methods for generating explicit water hydration positions. Formation of
      the hydrophobic surface regions owing to the structure of the first hydration
      shell can be computationally simulated by a small radial increment in solvent
      accessible polar atoms, followed by calculation of the remaining exposed
      hydrophobic patches. We demonstrate that a radial increase of 0.35-0.50 A
      resembles the effect of tightly bound water on the organization of the
      hydrophobic part of the solvent-accessible surface.

PMID- 9010926
TI  - Homology modeling study of the human interleukin-7 receptor complex.
AB  - Following a recent model of human interleukin-7 (IL-7), we present here a
      modeling study of the extracellular part of the human IL-7 receptor complex,
      including the IL-7 specific (IL-7R) and the common gamma (gamma c) chains. The
      investigation is based on structural homology to the complex of human growth
      hormone (hGH) bound to its receptor (hGHR). For domain 1 of IL-7R two different
      models are presented which differ in the alignment to hGHR in three regions.
      However, these differences affect binding to IL-7 in only one region, at the
      interface between loop EF of domain 1 of IL-7R and helix C of IL-7. The disulfide
      pattern in domain 1 of IL-7R is predicted to deviate from that observed in hGHR
      in that the C'-E disulfide (hGHR) is replaced by a C-C' cross-link. The
      prediction for the gamma c chain is compared with two previous studies. The
      models of the complex provide insight into the binding of IL-7 to its receptor
      and have implications for the suggestion of mutagenesis experiments and the
      design of (ant)agonists.

PMID- 9010927
TI  - Molecular modeling and mechanism of action of human decay-accelerating factor.
AB  - A model of the regulatory region of human decay accelerating factor (DAF) was
      built based on the known coordinates of a fragment of the structurally and
      functionally homologous serum protein, factor H. According to this model, the
      four short consensus repeats (SCRs) in DAF are arranged in a helical fashion. A
      positively charged surface area on SCRs 2 and 3, two of the three repeating units
      essential for function, is postulated to be the primary recognition site for the
      C3 convertases C4b2a and C3bBb. This area encompasses a cavity on SCR 2, as well
      as part of the groove on the SCR 2-SCR 3 interface. Two additional surface
      depressions are centered around the C-terminal disulfide bridges of SCRs 3 and 4.
      These are likely to provide additional ligand binding sites. Based on this model
      in conjunction with sequence homology to the Ba fragment of factor B, a mechanism
      of DAF's accelerated convertase decay action is postulated.

PMID- 9010928
TI  - Structural comparison of major histocompatibility complex class I molecules and
      homology modelling of five distinct human leukocyte antigen-A alleles.
AB  - The peptide complexes of 19 major histocompatibility complex class I alpha 1 and
      alpha 2 domains have been compared to identify similarities that can be
      interpreted as constraints necessary for the function or stability of the
      molecule. It was found that nearly half of the residues maintained their side
      chain conformations (or had no side chain), with the remaining residues being
      highly solvent exposed and/or polymorphic. Seven hydrogen bonds between the
      molecule and peptide are conserved in all the structures and serve to orientate
      the ends of the peptide in the binding groove. Furthermore, the general
      orientations of most residue side chains in the peptide are similar. Based on
      these constraints, homology models for the distinct human leukocyte antigen-A
      alleles A*0302, A*2403, A*2603, A*3101 and A*8001 have been constructed and the
      implications for peptide binding discussed. The models provide a useful framework
      from which to engineer allele-specific peptides with a high binding affinity.

PMID- 9010929
TI  - Semi-empirical simulation of Zn/Cd binding site preference in the metal binding
      domains of mammalian metallothionein.
AB  - Metallothionein, a two-domain protein, naturally binds seven gram atoms of
      divalent ions such as Zn and Cd. Four of the metals (M1, M5, M6 and M7) are found
      in the alpha-domain and three (M2, M3 and M4) in the beta-domain. Previous
      studies have shown that metals in the beta-domain are more readily exchangeable,
      and the level of avidity is site specific. By semi-empirical MNDO modified
      neglect of diatomic overlap calculations, we found the tendency of binding energy
      for Cd to be M4 > M2 > M3 [corrected] in the beta-cluster and M5 > M7 > M1, M6 in
      the alpha-cluster. Thus, the replacement of Zn by Cd can be expected to follow
      the order M4-->M2-->M3 in the beta-domain and M5-->M7-->M1 or M6 in the alpha
      domain. This is reflected by energy differences computed with a series of
      simulated structures derived from either X-ray crystallography or NMR
      coordinates.

PMID- 9010930
TI  - Independent self-assembly of cadmium-binding alpha-fragment of metallothionein in
      Escherichia coli without participation of beta-fragment.
AB  - We examined the independent self-assembly of the alpha- and beta-fragments of
      human metallothionein (MT) into cadmium-binding conformation in an Escherichia
      coli expression system, in addition to wild-type MT expression. The expressed
      alpha-fragment formed independently the structure of a metal-binding cluster
      without the aid of the beta-fragment. The alpha-fragment and wild-type MT
      expressed in E.coli were purified and analyzed for their biochemical and
      spectroscopic properties. The apparent cadmium binding of the alpha-fragment was
      approximately 12-fold greater than that for the wild-type MT, whereas in other
      respects the studied biochemical properties were similar. In contrast, we were
      unable to obtain any independently expressed beta-fragment as the cadmium-binding
      form in this study. Possible explanations for this phenomenon are discussed.

PMID- 9010931
TI  - Analysis of structural determinants of the stability of thermolysin-like
      proteases by molecular modelling and site-directed mutagenesis.
AB  - The thermolysin-like protease (TLP) produced by Bacillus stearothermophilus CU21
      (TLP-ste) differs at 43 positions from the more thermally stable thermolysin
      (containing 316 residues in total). Of these differences, 26 were analysed by
      studying the effect of replacing residues in TLP-ste by the corresponding
      residues in thermolysin. Several stabilizing mutations were identified but,
      remarkably, considerable destabilizing mutational effects were also found. A Tyr
      rich three residue insertion in TLP-ste (the only deletional/insertional
      difference between the two enzymes) appeared to make an important contribution to
      the stability of the enzyme. Mutations with large effects on stability were all
      localized in the beta-pleated N-terminal domain of TLP-ste, confirming
      observations that this domain has a lower intrinsic stability than the largely
      alpha-helical C-terminal domain. Rigidifying mutations such as Gly58-->Ala and
      Ala69-->Pro were among the most stabilizing ones. Apart from this observation,
      the analyses did not reveal general rules for stabilizing proteins. Instead, the
      results highlight the importance of context in evaluating the stability effects
      of mutations.

PMID- 9010932
TI  - Identification of two glutamic acid residues essential for catalysis in the beta
      glycosidase from the thermoacidophilic archaeon Sulfolobus solfataricus.
AB  - The Sulfolobus solfataricus, strain MT4, beta-glycosidase (Ss beta-gly) is a
      thermophilic member of glycohydrolase family 1. To identify active-site residues,
      glutamic acids 206 and 387 have been changed to isosteric glutamine by site
      directed mutagenesis. Mutant proteins have been purified to homogeneity using the
      Schistosoma japonicum glutathione S-transferase (GST) fusion system. The
      proteolytic cleavage of the chimeric protein with thrombin was only obtainable
      after the introduction of a molecular spacer between the GST and the Ss beta-gly
      domains. The Glu387-->Gln mutant showed no detectable activity, as expected for
      the residue acting as the nucleophile of the reaction. The Glu206-->Gln mutant
      showed 10- and 60-fold reduced activities on aryl-galacto and aryl-glucosides,
      respectively, when compared with the wild type. Moreover, a significant Km
      decrease with p/o-nitrophenyl-beta-D-glucoside was observed. The residual
      activity of the Glu206-->Gln mutant lost the typical pH dependence shown by the
      wild type. These data suggest that Glu206 acts as the general acid/base catalyst
      in the hydrolysis reaction.

PMID- 9010933
TI  - Relationship between thermal stability, degradation rate and expression yield of
      barnase variants in the periplasm of Escherichia coli.
AB  - An advantage of exporting a recombinant protein to the periplasm of Escherichia
      coli is decreased proteolysis in the periplasm compared with that in the
      cytoplasm. However, protein degradation in the periplasm also occurs. It has been
      widely accepted that the thermodynamic stability of a protein is an important
      factor for protein degradation in the cytoplasm of E.coli. To investigate the
      effect of the thermodynamic stability of an exported protein on the extent of
      proteolysis in the periplasm, barnase (an extracellular ribonuclease from
      Bacillus amyloliquefaciens) fused to alkaline phosphatase leader peptide was used
      as a model protein. A set of singly or doubly mutated barnase variants were
      constructed for export to the E.coli periplasm. It was found that the half-life
      of the barnase variants in vivo increased with their thermodynamic stability in
      vitro. A dominant factor for the final yield of exported barnase was not
      exportability but the turnover rate of the barnase variant. The yield of a
      stabilized mutant was up to 50% higher than that of the wild type. This suggests
      that exporting a protein to the periplasm and using protein engineering to
      enhance the stability can be combined as a strategy to optimize the production of
      recombinant proteins.

PMID- 9010934
TI  - Ligand-induced conformational changes in wild-type and mutant yeast pyruvate
      kinase.
AB  - A mutant form of pyruvate kinase in which serine 384 has been mutated to proline
      has been engineered in the yeast Saccharomyces cerevisiae. Residue 384 is located
      in a helix in a subunit interface of the tetrameric enzyme, and the mutation was
      anticipated to alter the conformation of the helix and hence destabilize the
      interface. Previous results indicate that the mutant favours the T quaternary
      conformation over the R conformation, and this is confirmed by the results
      presented here. Addition of phosphoenol-pyruvate (PEP), ADP and fructose-1, 6
      bisphosphate (Fru-1.6-P2) singly to the wild-type and mutant enzymes results in a
      significant quenching of tryptophan fluorescence (12-44%), and for Fru-1,6-P2, a
      red shift of 15 nm in the emission maximum. Fluorescence titration experiments
      showed that PEP, ADP and Fru-1,6-P2 induce conformations which have similar
      ligand-binding properties in the wild-type and mutant enzymes. However, the Fru
      1,6-P2 induced conformation is demonstrably different from those induced by
      either ADP or PEP. The enzymes differ in their susceptibility to trypsin
      digestion and N-ethylmaleimide inhibition. The thermal stability of the enzyme is
      unaltered by the mutation. Far-UV CD spectra show that both enzymes adopt a
      similar overall secondary structure in solution. Taken together, the results
      suggest that the Ser384-Pro mutation causes the enzyme to adopt a different
      tertiary and/or quaternary structure from the wild-type enzyme and affects the
      type and extent of the conformational changes induced in the enzyme upon ligand
      binding. A simplified minimal reaction mechanism is proposed in which the R and T
      states differ in both affinity and kcat. Thus, in terms of the models of
      cooperativity and allosteric interaction, pyruvate kinase is both a K and a V
      system.

PMID- 9010935
TI  - Study of antibody-antigen interaction through site-directed mutagenesis of the VH
      region of a hybrid phage-antibody fragment.
AB  - An important aspect of the study of antibody structure-function relationships
      involves analysis of natural or synthetic mutations of antigen-combining sites.
      The anti-hen egg lysozyme monoclonal antibody HyHEL-10 has been a focus for
      antibody structure-function studies. We have displayed on bacteriophage of a
      hybrid single chain Fv, containing the light chain variable region of HyHEL-10
      and the heavy chain variable region of a structurally related but functionally
      distinct antibody, AS32. By using a combination of site-directed mutagenesis,
      complementary determining region grafting and molecular modeling, we have
      identified a number of contact and non-contact residues that are important in the
      affinity of HyHEL-10 for lysozyme. In particular, the heavy chain variable region
      framework residue at position 94 was shown to be an important determinant of high
      affinity binding. The phage display approach eliminates the need for purification
      of antibodies and, when used in combination with polymerase chain reaction for
      variable region sequence mutagenesis, facilitates the rapid generation and
      characterization of mutant antibodies.

PMID- 9010936
TI  - Specific antimicrobial and hemolytic activities of 18-residue peptides derived
      from the amino terminal region of the toxin pardaxin.
AB  - Peptides are part of the host defense system against bacteria and fungi in
      species right across the evolutionary scale. However, endogenous antibacterial
      peptides are often composed of 25 residues or more and, therefore, are not ideal
      for therapeutic use. Hence it is of considerable interest to design and engineer
      short peptides having antimicrobial activity. Peptides composed of 18 amino
      acids, derived from the N-terminal region of the 33-residue toxin pardaxin (PX),
      GFFALIPKIISSPLFKTLLSAVGSALSSSGEQE, were synthesized and examined for biological
      activities. Peptide corresponding to the 1-18 stretch of PX exhibited
      antimicrobial activity only against Escherichia coli and not against Gram
      positive microorganisms. The peptide also did not possess hemolytic activity.
      Replacement of P7 by A resulted in a peptide possessing both antibacterial and
      hemolytic activity. Substitution of both K residues by Q in the 'A' analog
      resulted in a peptide having only hemolytic activity. Conformational analysis of
      these peptides and investigation of their model membrane permeabilizing
      activities indicated that selective activity can be explained by their
      biophysical properties. Hence, by a rational design approach based on biophysical
      principles, it should be possible to generate short peptides having specific
      biological activity.

PMID- 9010937
TI  - Expression in insect cells and purification of a catalytically active recombinant
      human gastric lipase.
AB  - Human gastric lipase (HGL) cDNA was synthesized by RT-PCR amplification and
      cloned into the PVL 1392 baculovirus transfer vector. The recombinant transfer
      vector was cotransfected with a modified baculovirus DNA (Baculogold) which
      contains a lethal deletion. Cotransfection of baculovirus DNA with the
      recombinant transfer vector rescues the lethal deletion of this virus DNA and
      reconstitutes viable virus particles inside the transfected insect cells. BTI-TN
      5B1-4 insect cells (also called High Five cells) were used to express recombinant
      HGL. The level of HGL secretion was approximately 32 mg/l of culture medium. The
      insect cells also accumulated HGL intracellularly, which indicated the existence
      of rate-limiting steps in the secretion of HGL. Therefore we investigated the
      effect of replacing the HGL signal peptide (SP) by other SP of secreted proteins.
      The honeybee melittin SP and the human pancreatic lipase (HPL) SP were tested.
      The fusion of HGL with HPL SP resulted in a 2-fold increase in the amount of
      lipase secreted from the insect cells. The recombinant active HGL was not
      processed at the expected cleavage site of the natural enzyme, however, but at
      residue +3. On the other hand, High Five cells transfected with the vector
      encoding HGL fused to the melittin SP did not secrete any detectable active HGL.
      Recombinant HGL was identified using the Western blot procedure with rabbit
      polyclonal antibodies. The protein migrated with an apparent molecular mass of 45
      kDa under SDS-PAGE analysis (compared with 50 kDa in the case of natural HGL),
      indicating that the insect cells have only a limited capacity to glycosylate HGL.
      The maximum specific activities of the recombinant lipase were 434, 730 and 562
      units/mg using long-chain (Intralipid), medium-chain (trioctanoylglycerol) and
      short-chain (tributyroylglycerol) triacylglycerols, respectively.

PMID- 9010938
TI  - Expression, purification and characterization of recombinant crambin.
AB  - Crambin, a small hydrophobic protein (4.7 kDa and 46 residues), has been
      successfully expressed in Escherichia coli from an artificial, synthetic gene.
      Several expression systems were investigated. Ultimately, crambin was
      successfully expressed as a fusion protein with the maltose binding protein,
      which was purified by affinity chromatography. Crambin expressed as a C-terminal
      domain was then cleaved from the fusion protein with Factor Xa protease and
      purified. Circular dichroism spectroscopy and amino acid analysis suggested that
      the purified material was identical to crambin isolated from seed. For positive
      identification the protein was crystallized from an ethanol-water solution, by a
      novel method involving the inclusion of phospholipids in the crystallization
      buffer, and then subjected to crystallographic analysis. Diffraction data were
      collected at the Brookhaven synchrotron (beamline-X12C) to a resolution of 1.32 A
      at 150 K. The structure, refined to an R value of 9.6%, confirmed that the cloned
      protein was crambin. The availability of cloned crambin will allow site-specific
      mutagenesis studies to be performed on the protein known to the highest
      resolution.

PMID- 9010939
TI  - Synthesis of a squash-type protease inhibitor by gene engineering and effects of
      replacements of conserved hydrophobic amino acid residues on its inhibitory
      activity.
AB  - Cucurbita maxima trypsin inhibitor I (CMTI-I), a member of the squash-type
      protease inhibitor family, is composed of 29 amino acids and shows strong
      inhibition of trypsin by its compact structure. To study the structure-function
      relationship of this inhibitor using protein engineering methods, we constructed
      an expression system for CMTI-I as a fused protein with porcine adenylate kinase
      (ADK). A Met residue was introduced into the junction of ADK and CMTI-I to cleave
      the fusion protein with CNBr, whereas a Met at position 8 of authentic CMTI-I was
      replaced by Leu. Escherichia coli JM109 transformed with the constructed plasmid
      expressed the fused protein as an inclusion body. After cleavage of the expressed
      protein with CNBr, fully reduced species of CMTI-I were purified by reversed
      phase HPLC and then oxidized with air by shaking. For efficient refolding of CMTI
      I, we used 50 mM NH4HCO3 (pH 7.8) containing 0.1% PEG 6000 at higher protein
      concentration. Strong inhibitory activity toward trypsin was detected only in the
      first of three HPLC peaks. The inhibitor constant of CMTI-I thus obtained, in
      which Met8 was replaced by Leu, was 1.4 x 10(-10) M. The effect of replacement of
      Met with Leu at position 8 was shown to be small by comparison of the inhibitor
      constant of authentic CMTI-III bearing Lys at position 9 (8.9 x 10(-11) M) with
      that of its mutant bearing Leu at position 8 and Lys at position 9 (1.8 x 10(-10)
      M). To investigate the role of the well conserved hydrophobic residues of CMTI-I
      in its interaction with trypsin, CMTI-I mutants in which one or all of the four
      hydrophobic residues were replaced by Ala were prepared. The inhibitor constants
      of these mutants indicated that those with single replacements were 5-40 times
      less effective as trypsin inhibitors and that the quadruple mutant was
      approximately 450 times less effective, suggesting that the hydrophobic residues
      in CMTI-I contribute to its tight binding with trypsin. However, each mutant was
      not converted to a temporary inhibitor.

PMID- 9010940
TI  - Identification of the epidural space: loss of resistance to air or saline?

PMID- 9010941
TI  - Identification of the epidural space: is loss of resistance to air a safe
      technique? A review of the complications related to the use of air.
AB  - BACKGROUND AND OBJECTIVES: The major determinant of successful epidural
      anesthesia is the localization of the epidural space. The manual loss of
      resistance technique is widely used by anesthesiologists in identifying the
      epidural space. Should air or saline be used in detecting the point of loss of
      resistance? No consensus exists as to which technique is superior, and individual
      providers currently use the technique with which they are most comfortable. The
      incidence of adverse effects associated with the use of epidural air is unknown
      and may be underreported as the effects may be unrecognized or considered
      trivial. The authors comprehensively review the complications of epidural air
      from published reports. METHODS: Using the appropriate key words, the authors
      searched the Medline (National Library of Congress) scientific data bank from
      1966 to 1995, for case reports of epidural complications. RESULTS: There are few
      prospective, controlled, double-blinded studies comparing the relative merits of
      using air versus saline for the loss of resistance technique of epidural
      placement. There are, however, numerous case reports. Complications associated
      with the use of air for the loss of resistance technique included pneumocephalus,
      spinal cord and nerve root compression, retroperitoneal air, subcutaneous
      emphysema, and venous air embolism. Additionally, inadequate analgesia and
      paresthesia have been associated with the loss of resistance technique using air.
      Transient and permanent neurologic sequelae have been attributed to some of the
      complications. The simultaneous administration of nitrous oxide and positive.
      Pressure ventilation has also been reported to expand localized collections of
      air, resulting in heightened symptoms. CONCLUSIONS: The potential complications
      associated with the use of air for identifying the epidural space with the loss
      of resistance technique may outweigh the benefits. The use of saline to identify
      the epidural space may help to reduce the incidence of these complications.

PMID- 9010942
TI  - Epidural analgesia improves outcome following pediatric fundoplication. A
      retrospective analysis.
AB  - BACKGROUND AND OBJECTIVES: Nissen fundoplication is a common procedure in high
      risk pediatric patients. This cohort study evaluated the influence of epidural
      versus intravenous opioid analgesia on the postoperative course of infants and
      children undergoing fundoplication. METHODS: A retrospective review was made of
      the perioperative courses of 155 consecutive patients, aged 1 month to 19 years,
      who underwent elective open fundoplication from January 1993 to October 1994. Of
      these 155 patients, 72 received perioperative analgesia with epidural opioids,
      while 83 received parenteral opioids. Outcome variables included major morbidity
      factors, recovery of bowel and bladder function, and economic impact. RESULTS:
      Patients in the epidural and parenteral groups did not differ with respect to
      age, weight, or associated preoperative medical diagnoses. The postoperative
      complication rate was significantly decreased in the epidural group (5.5% versus
      20%) (P < .001). In the epidural group 4 patients required mechanical ventilation
      for longer than 24 hours, compared with 15 in the parenteral group. Patients in
      the epidural group were discharged earlier from the hospital and incurred
      approximately 20% less in hospital charges on average than their cohorts in the
      intravenous group. CONCLUSIONS: These findings suggest that perioperative
      epidural analgesia, administered by a dedicated pain service, amy improve outcome
      in high-risk pediatric patients undergoing fundoplication.

PMID- 9010943
TI  - Transdermal fentanyl in postoperative pain.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to determine the safety and
      effectiveness of a transdermal fentanyl delivery system for the relief of pain
      following abdominal surgery. METHODS: In a nonblinded, noncrossover, placebo
      controlled study, 40 ASA I and II patients of both sexes, 18-69 years of age, who
      were scheduled for abdominal surgery under general anesthesia, were randomly
      divided into two groups of 20 patients each. Patients in group I received a
      transdermal patch containing 0.16 mg/cm2 of fentanyl, which was applied to the
      skin over the subclavian area 60 minutes before the induction of anesthesia. For
      body weight less than 60 kg, a 30 cm2 patch was applied, and for weight greater
      than 60 kg, a 40 cm2 patch was used. A second group of 20 patients received
      placebo patches of identical size. Approximately 20 to 30 minutes before the
      expected end of surgery, 60 mg ketorolac was administered intramuscularly.
      Patients were observed for 36 hours after placement of the patch. If patients
      reported their pain at rest as 5 or greater at rest on a 0-10 visual analog
      scale, they were given 30-mg increments of ketorolac 5 to 7 hours apart. If this
      regimen did not relieve their pain, they received 1,300 mg acetaminophen between
      two ketorolac doses. If despite this, they still had pain 30 minutes afterward,
      intravenous morphine was given, and the patients were excluded from further
      study. The patch was removed in four patients in the fentanyl group and seven in
      the placebo group for various reasons, which included, inadequate pain relief
      requiring additional analgesia postoperatively and more than 1 microgram/kg of
      sufentanil given intraoperatively or immediately prior to the end of surgery.
      During the 36-hour observation period, 30 doses of 30 mg ketorolac and 14 doses
      of 1.3 g acetaminophen were given to 13 patients in the placebo group and 18
      doses of ketorolac and 8 doses of acetaminophen were administered to 16 in the
      fentanyl group. RESULTS: The differences in postoperative analgesic requirements
      were significant. Plasma fentanyl concentrations at 12 and 24 hours after the
      application of the fentanyl patch were 0.98 +/- 0.14 ng/mL and 1.22 +/- 0.17
      ng/mL, respectively. At 8, 16, 24, and 36 hours after application of the patch,
      the pain relief, assessed by a VAS at rest and with movement, was similar in the
      two groups. In the fentanyl and control groups, 12 and 5 patients, respectively,
      experienced nausea, and 2 and 3 patients, respectively, vomited. CONCLUSIONS:
      Similar postoperative analgesia was achieved with less parenteral analgesics in
      patients who received transdermal fentanyl preoperatively than in control
      patients. Fentanyl, 50-75 micrograms/h, administered in a transdermal delivery
      system, did not depress respiratory rate or hemoglobin oxygen saturation.
      Although the exact role of continuously administered opioids in managing acute
      postoperative pain has yet to be clearly defined, it is concluded that if
      properly used, this new transdermal device can be effective in providing a
      background of analgesia, which may assist in the management of acute
      postoperative pain as well as some chronic pain states.

PMID- 9010944
TI  - Intravenous regional anesthesia with 0.5% articaine, 0.5% lidocaine, or 0.5%
      prilocaine. A double-blind randomized clinical study.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the
      effectiveness of three local anesthetic agents for intravenous regional
      anesthesia in the upper limb. Side effects and plasma concentrations of the drugs
      in the doses administered for IVRA were also studied. METHODS: Thirty patients in
      ASA groups I and II received intravenous regional anesthesia for surgery of the
      upper limb. In a double-blind prospective study, they were randomly allocated to
      receive one of three local anesthetics: articaine, lidocaine, or prilocaine.
      Patients received 40 mL of a 0.5% solution of the local anesthetic. The onset
      time of sensory block was assessed by pinprick and the extent of motor block was
      was scored as 0-3. Plasma concentrations of local anesthetics were determined in
      all patients from serial arterial blood samples drawn at predetermined times
      before and after tourniquet release. RESULTS: The onset time of sensory block was
      significantly shorter (2.5 minutes) in the articaine group than in the lidocaine
      group (11.1 minutes) or the prilocaine group (10.9 minutes) (Scheffe, P < .05).
      Development of motor block was equal in all three groups (score 2). Estimation of
      plasma concentrations by high performance liquid chromatography showed that the
      peak level in all 30 patients was reached immediately after release of the
      tourniquet; plasma concentrations thereafter gradually declined. Maximum
      concentrations of articaine, lidocaine, and prilocaine were, 1.85, 8.5, and 4.4
      micrograms/mL, respectively. No signs of local anesthetic toxicity of the
      cardiovascular or central nervous systems were seen. CONCLUSION: Articaine had
      the fastest onset of sensory block and the lowest peak plasma concentration of
      the three local anesthetics when used for intravenous regional anesthesia.

PMID- 9010945
TI  - Extended epidural catheter infusions with analgesics for patients with noncancer
      pain at their homes.
AB  - BACKGROUND AND OBJECTIVES: Patients with severe, noncancer pain unresponsive to
      epidural steroid injections are frequently referred for implantation of a
      permanent intraspinal device or for surgery. An alternative approach has been
      evaluated, which involves extended epidural catheter infusions of analgesics.
      METHODS: Observations were made in 551 adult patients with severe low back pain
      due to a variety of nonmalignant causes, who were treated in an ambulatory
      setting with a total of 3,108 temporary lumbar epidural catheter infusions of low
      dose bupivacaine and fentany via disposable infusion pumps. RESULTS: All but a
      few treatments resulted in good to excellent pain relief, and most permitted
      patients to increase their physical activities to near normal levels. The cost of
      this approach was lower than that associated with insertion of an implantable
      infusion pump. CONCLUSIONS: Temporary lumbar epidural catheter infusions
      represent an option between lumbar epidural steroid injections and more invasive
      and expensive modalities. The technique is effective in relieving chronic low
      back pain for extended periods, reducing its long-term intensity, and in some
      cases abolishing it.

PMID- 9010946
TI  - The hypothesis that antagonism of fentanyl analgesia by 2-chloroprocaine is
      mediated by direct action on opioid receptors.
AB  - BACKGROUND AND OBJECTIVES: Although 2-chloroprocaine continues to be a useful
      drug for epidural anesthesia in obstetrics, it has the anomalous action of
      decreasing the analgesic effectiveness of subsequently administered epidural
      fentanyl. Some investigators have suggested that 2-chloroprocaine may act at an
      opioid receptor site to antagonize the effects of fentanyl. The purpose of our
      studies was to investigate this hypothesis. METHODS: Radioligand binding assays
      using the mu and kappa opioid receptor-selective radioligands [3H]-DAMGO and [3H]
      U69,593, respectively, were performed to determine the potencies of lidocaine, 2
      chloroprocaine, and 2-chloroprocaine metabolites at the mu and kappa opioid
      receptor sites. Electrophysiologic experiments in in vitro hippocampal slice
      preparations were then used to examine the effects of 2-chloroprocaine at these
      opioid receptor subtypes. RESULTS: Lidocaine caused a partial reduction of [3H]
      DAMGO binding, which was dose-limited owing to the solubility of lidocaine. 2
      Chloroprocaine caused complete displacement of [3H]-DAMGO binding, with a median
      effective concentration of 1.44 +/- 0.36 mM. The EC50 values for [3H]-U69,593
      displacement were 177 +/- 47 microM for 2-chloroprocaine and 2.53 +/- 0.48 mM for
      lidocaine. Assuming a competitive interaction between anesthetic and opioid, the
      Ki value for 2-chloroprocaine was 435 microM at mu receptors and 49 microM at
      kappa receptors. In the mu activity bioassay, 2-chloroprocaine reversed the
      increased neuronal excitability caused by fentanyl, but this effect was further
      reduced by naloxone. In addition, 2-chloroprocaine did not reverse the after
      depolarization caused by fentanyl. In the kappa activity bioassay, 2
      chloroprocaine produced effects similar to the kappa agonist U69, 593, but these
      were not antagonized by naloxone. CONCLUSIONS: Although 2-chloroprocaine has
      binding affinity at mu and kappa opioid receptor sites, it does not appear to act
      through an opioid receptor to antagonize the physiologic effects of fentanyl.

PMID- 9010947
TI  - Spinal anesthesia reduces oxygen consumption in diabetic patients prior to
      peripheral vascular surgery.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the effect
      of spinal anesthesia in VO2 in a uniform high-risk patient population and also
      the relationship between dermatomal level of block and VO2, neither of which has
      been investigated previously. METHODS: The effect of spinal anesthesia on VO2 was
      studied in 17 diabetic patients undergoing lower limb peripheral vascular
      surgery. Measurements were made before and 15 minutes after administration of a
      tetracaine spinal anesthetic. Values for VO2 and oxygen delivery (DO2) were
      derived from cardiac output as measured by thermodilution, hemoglobin
      concentration, and arterial and mixed venous blood gas analysis. The dermatomal
      level of the sensory block was determined by use of a hand-held nerve stimulator.
      RESULTS: Mean VO2 decreased by 27.7% (P = .001) (95% confidence limits, decrease
      of 22.4-90.4%). Mean DO2 and arterial blood gases were unchanged, and the mean
      postspinal oxygen extraction ratio (VO2/DO2) decreased by 20.5% (P = .002) (95%
      confidence limits, decrease of 9.1-32.3%). There was a relationship between
      changes in VO2 and sensory block height (P = .029). CONCLUSIONS: Spinal
      anesthesia in diabetic patients is associated with a reduction in VO2, the extent
      of which appears to be, at least in part, a function of the level of spinal
      sensory block.

PMID- 9010948
TI  - Effect of local methylprednisolone on pain in a nerve injury model. A pilot
      study.
AB  - BACKGROUND AND OBJECTIVES: Local injections of corticosteroids are frequently
      used in the treatment of regional pain. The rationale for this is not very clear,
      since an inflammatory cause of pain is rarely evident. There are few data on the
      effect of corticosteroids on nociception in experimental animals. However,
      corticosteroids have been found to suppress ectopic discharges from experimental
      neuromas and to have a short-lasting suppressive effect on transmission in normal
      C-fibers. In this study the influence of a locally applied depot form of a
      corticosteroid on neuropathic pain was investigated in a rat model. METHODS:
      Peripheral mononeuropathy was induced with a chronic constriction injury to the
      left sciatic nerve. This procedure has previously been shown to produce various
      signs of disturbed sensibility, including heat hyperalgesia, mechanical
      allodynia, and mechanical hyperalgesia, indicating that a neuropathic pain-like
      condition has developed. The occurrence of neuropathic pain in these animals was
      confirmed with behavioral testing after 9 days. The site of injury was then
      reexposed and treated locally with either a depot form of a corticosteroid
      (methylprednisolone) or saline. The animals were then tested for another 11 days.
      RESULTS: The heat hyperalgesia and mechano-allodynia but not the mechano
      hyperalgesia were depressed in the animals receiving the corticosteroid but not
      in those treated with saline. The effect remained during the whole 11-day test
      period. CONCLUSIONS: It is hypothesized that the corticosteroid acts by
      suppression of ectopic neural discharges from the injured nerve fibers.

PMID- 9010949
TI  - Role of needle gauge and tip configuration in the production of lumbar puncture
      headache.
AB  - BACKGROUND AND OBJECTIVES: Postdural puncture headache (PDPH) is a morbidity that
      occurs frequently after lumbar puncture. The purpose of this study was to
      evaluate the role of needle diameter and tip configuration in causing PDPH. The
      incidence of PDPH was evaluated in parturients because this group of patients is
      at high risk for developing PDPH and because they often undergo lumbar puncture
      for spinal anesthesia. METHODS: The incidence of PDPH after spinal anesthesia
      with 26- and 27-gauge Quincke and 25-gauge Whitacre needles was studied in a
      series of 4,125 parturients undergoing spinal anesthesia over a 4-year period.
      Data were also collected on the incidence of PDPH with 17-gauge Huber-tipped
      Weiss needles in 21,578 parturients receiving lumbar epidural analgesia and/or
      anesthesia over the same interval. Additionally, the need to treat PDPH with
      epidural blood patch in all of these patients was studied. RESULTS: The incidence
      of PDPH was 5.2% with 26-gauge Quincke needles (1987-1989), 2.7% with 27-gauge
      Quincke needles (1989-1990), and 1.2% with 25-gauge Whitacre needles (1990-1991).
      During the same periods, the incidence of PDPH with 17-gauge Weiss needles
      averaged 1.1%, 1.7% and 1.2%, respectively. As compared with the 26-gauge Quincke
      needle, there was a lower incidence of PDPH with the 27-gauge Quincke (P < .006)
      and 25-gauge Whitacre spinal needles (P < .001). The incidence of PDPH with the
      25-gauge Whitacre needle was less than that with the 27-gauge Quincke needle (P <
      .05), and it was similar to the overall rate of headache, which occurs
      occasionally from accidental dural puncture during the performance of lumbar
      epidural analgesia/anesthesia for labor and cesarean delivery (P = .974). The
      need for treating PDPH with epidural blood patching was greatest with the 17
      gauge Weiss epidural needle (75.3% of cases), but was similar with the various
      spinal needles (13-39%). However, because the Whitacre needle produced the fewest
      PDPHs, it was associated with the lowest absolute requirement for epidural blood
      patching. CONCLUSIONS: The morbidity associated with lumbar puncture can be
      decreased by selecting the proper needle gauge and tip configuration. Use of the
      smallest gauge needle and one that has a noncutting Whitacre tip produces the
      lowest incidence of PDPH in parturients, a group of patients at increased risk
      for developing PDPH.

PMID- 9010950
TI  - Failure of meperidine to anesthetize human median nerve. A blinded comparison
      with lidocaine and saline.
AB  - BACKGROUND AND OBJECTIVES: Although meperidine safely produces clinical spinal
      anesthesia, the responsible mechanism is unknown. This study was undertaken to
      test the possibility that this drug acts as a local anesthetic by investigating
      its ability to inhibit conduction in a human peripheral nerve. METHODS: In a
      blinded fashion, the abilities of 5-mL injections of meperidine (0.5% and 1.5%),
      lidocaine (0.25%), and saline to produce median nerve block were tested in eight
      volunteer subjects, and these four solutions were compared with standard local
      anesthetic solutions that had been tested in previous studies. The extent of
      local anesthesia was measured objectively by electrodiagnostic tests, namely,
      compound motor action potentials (CMAPs) and sensory nerve action potentials
      (SNAPs), as well as by qualitative tests of sensation. RESULTS: Lidocaine (0.25%)
      prolonged median SNAP latency from 3.1 ms to 3.3 ms (P < .015) and prolonged mean
      CMAP latency from 4.1 ms to 4.7 ms (P < .002). The SNAP amplitude trended
      downward after lidocaine (0.25%), but the decrease did not reach statistical
      significance (35 microV to 25 microV, P < .19). Neither meperidine solution (0.5%
      or 1.5%) nor saline inhibited SNAP or CMAP amplitudes or prolonged SNAP or CMAP
      latencies. Also, in contrast to previous findings with more potent local
      anesthetic solutions (eg, lidocaine 1%, mepivacaine 1%, and bupivacaine 0.33%),
      none of the four solutions tested in this study altered subjective sensations of
      hot, cold, or pinprick. Meperidine 1.5% produced systemic side effects, including
      vertigo, nausea, and flushing, in all subjects. CONCLUSIONS: Meperidine produced
      no signs of local anesthesia, even when given at a dose (75 mg) and concentration
      (1.5%) that consistently produced systemic side effects. Thus, the coequivalent
      ability of meperidine and lidocaine to produce spinal anesthesia contrasts with
      their discordant ability to produce local anesthesia. This disparity suggests
      that meperidine may produce spinal anesthesia through mechanisms other than
      inhibition of sodium channel function.

PMID- 9010951
TI  - A chronic model for experimental investigation of epidural anesthesia in the
      rabbit.
AB  - BACKGROUND AND OBJECTIVES: A rabbit chronic model has been developed for
      investigation of epidural anesthesia without surgery. METHODS: A catheter was
      implanted via a nontraumatic route in the lumbar epidural space between the apex
      coccis sacri and the first vertebra coccygea after a 1-cm incision was made in
      the skin at the root of the tail. The ligamentum was punctured to allow the
      catheter to slide gently 10 cm into the epidural space and avoid subperiosteal
      soft tissue dissection. The motor block effects of epidural lidocaine and
      bupivacaine were studied 1 week after implantation. Three injections of lidocaine
      1% (group I) or 2% (group II) or bupivacaine 0.25% (group III) or 0.5% (group IV)
      were given at 48-hour intervals to four rabbits in each group. Increasing
      concentrations (0.5%, 1.0%, and 2.0%) of lidocaine and bupivacaine (0.125, 0.25,
      and 0.5%) were injected into eight rabbits in each of groups V and VI. The spinal
      cord and meninges were examined histopathologically in eight other chronically
      implanted rabbits that received no drugs. RESULTS: Catheters were kept in place
      during 2 months in 40 rabbits without neurologic disturbance, discomfort,
      infection or weight loss. Complete motor block was observed during a mean 27, 43,
      and 51 minutes with increasing doses of lidocaine. Administration of bupivacaine
      0.125% led to incomplete motor deficit in three rabbits, whereas all other
      rabbits exhibited complete motor block, lasting a mean of 26, 53, and 93 minutes
      for increasing doses. Linear relationships were found between the concentration
      of each drug and the duration of motor block (r = .902, P < .001 for lidocaine;
      and r = .857, P < .001 for bupivacaine). Repeated injections of local anesthetics
      produced consistent durations of motor block (Bland and Altman test). No
      significant histologic changes were observed. CONCLUSION: This rabbit model
      appears to be a suitable tool for evaluating motor block of epidural agents under
      standardized experimental conditions.

PMID- 9010952
TI  - Subarachnoid sufentanil for extracorporeal shock lithotripsy.
AB  - BACKGROUND AND OBJECTIVES: Many different anesthetic techniques have been used
      for extracorporeal shock wave lithotripsy, each with its own benefits and
      disadvantages. A study was made to determine the efficacy and safety of
      subarachnoid sufentanil as an analgesic technique for lithotripsy. METHODS: Eight
      consecutive patients from the University of Michigan Medical Center and twelve
      consecutive patients from the University of Vermont College of Medicine were
      retrospectively studied. The need for additional anesthesia, incidence of adverse
      effects, and discharge times were assessed. RESULTS: Of the 20 patients, 18 were
      treated successfully with subarachnoid sufentanil. One patient had inadequate
      anesthesia. One procedure was postponed owing to intractable pruritus. Adverse
      effects occurred in four patients and were successfully treated. The mean
      discharge time was 132 minutes, which is comparable with those of other
      anesthetic methods. CONCLUSIONS: Subarachnoid sufentanil is a safe and effective
      technique for lithotripsy. A prospective study to compare it with other methods
      is justified.

PMID- 9010953
TI  - Myofascial pain syndrome and trigger-point management.
AB  - BACKGROUND AND OBJECTIVES: Myofascial pain syndrome (MPS) is a common condition
      often resulting in referral to a pain clinic. The epidemiology, pathogenesis, and
      various diagnostic tools are reviewed, and a variety of treatment methods are
      discussed. METHODS: Extensive periodical literature and textbooks are reviewed,
      and selected manuscripts are critically analyzed. RESULTS: The incidence of MPS
      with associated trigger points appears to vary between 30 and 85% of people
      presenting to pain clinics, and the condition is more prevalent in women than in
      men. Patients complain of regional persistent pain, ranging in intensity and most
      frequently found in the head, neck, shoulders, extremities, and low back. Muscle
      histologic abnormalities have been described in some studies. Similarly,
      electromyographic, thermographic, and pressure algometric studies have
      inconsistently identified abnormalities. A multidisciplinary approach to
      treatment appears to be most beneficial and may include such modalities as
      trigger-point injections, dry needling, stretch and spray, and transcutaneous
      electrical nerve stimulation. CONCLUSIONS: The definitive pathogenesis of MPS is
      currently unknown, and no single diagnostic method is consistently positive.
      While trigger-point injection is the most widely employed method of treatment,
      other modes of therapy have also proved to be effective.

PMID- 9010954
TI  - Epidural anesthesia for extracorporeal shock wave lithotripsy in an
      achondroplastic dwarf.
AB  - BACKGROUND AND OBJECTIVES: A 66-year-old achondroplastic male dwarf with right
      ureteral stones presented for outpatient extracorporeal shock wave lithotripsy
      under epidural anesthesia. METHODS: The patient had marked lumbar lordosis and
      mild thoracic kyphosis. Although the epidural space was located easily at the L2
      3 interspace on the first attempt, the catheter could not be advanced beyond the
      Tuohy needle. On the second attempt, the epidural space was located easily at the
      L1-2 interspace, and the catheter was advanced without difficulty. RESULTS: A
      sensory block to the T2 level developed after administration of 2 mL of lidocaine
      1.5% with epinephrine 1:200,000 and 9 mL of lidocaine 2.0% with epinephrine
      1:200,000. Aside from a short period of mild, asymptomatic hypotension, the
      patient's intraoperative and postoperative courses were unremarkable.
      CONCLUSIONS: This case report and the available literature support the
      feasibility of epidural anesthesia in achondroplastic patients. Careful titration
      of the local anesthetic dose is recommended since achondroplastic patients may
      have extensive spread of epidural anesthesia.

PMID- 9010955
TI  - Doppler-assisted nerve block.

PMID- 9010956
TI  - Comments on study of spinal needle tips by Rosenberg et al.

PMID- 9010957
TI  - Brachial plexus anatomy.

PMID- 9010958
TI  - Characterisation of left ventricular relaxation in the isolated guinea pig heart.
AB  - The time constant of left ventricular pressure fall, tau, has frequently been
      used as a measure of myocardial relaxation in the blood-perfused, ejecting heart.
      The aim of the present study was to characterise tau in relation to beta
      adrenergic activation, coronary perfusion pressure and flow as well as cardiac
      oxygen supply and demand in the isolated, isovolumically beating heart.
      Therefore, tau was analysed from digitised left ventricular pressure data in a
      total of 23 guinea pig hearts perfused with saline at constant pressure (60
      cmH2O). The coronary venous adenosine concentration ([ADO]) served as an index of
      myocardial oxygenation. Isoprenaline (0.4-3.2 nmol l-1) decreased and propranolol
      (3-9 mumol l-1) increased tau dose-dependently (linear regression tau vs
      lg([isoprenaline]), r = 0.74; tau vs. lg([propranolol]), r = 0.66, both P <
      0.05). During graded reductions in cardiac oxygen supply from 96.1 +/- 12.6 (SEM)
      to 44.4 +/- 4.4 microliters min-1 g-1, tau was prolonged from 61.5 +/- 12.7 to
      109.9 +/- 22.6 ms while left ventricular developed pressure (LVDP) decreased from
      90.7 +/- 7.2 to 40.7 +/- 5.1 mmHg. In parallel, [ADO] increased from 23.7 +/- 9.1
      to 58.0 +/- 19.1 pmol ml-1 (P < 0.05). Increasing oxygen supply to 165.4 +/- 32.4
      microliters min-1 g-1 augmented LVDP to 102.7 +/- 7.3 mmHg but did not change tau
      or [ADO]. There was a dual response of tau to changes in cardiac oxygen supply or
      demand. As long as oxygen supply and demand matched, tau remained constant.
      However, when the oxygen supply was less than 100 microliters min-1 g-1, left
      ventricular relaxation was prolonged in parallel to the reduction in oxygen
      supply. In addition, a close relationship was observed between [ADO] as an
      indicator of myocardial oxygenation and tau (Spearman correlation, r = 0.99, P <
      0.005). We conclude that the time constant of left ventricular pressure fall,
      tau, sensitively reflects myocardial relaxation in the isolated, isovolumically
      beating guinea pig heart. Moreover, in this model left ventricular relaxation is
      not influenced by alterations in coronary perfusion pressure or flow as long as
      cardiac oxygen demand is matched by an adequate supply. Rather relaxation is
      strictly coupled to myocardial oxygenation as reflected by coronary venous
      adenosine concentrations.

PMID- 9010959
TI  - Esophageal anastomosis: an experimental model to study anastomotic healing and
      the use of lyophilized collagen.
AB  - This experimental study assessed the use of lyophilized collagen to reinforce
      cervical esophageal anastomosis in rabbits. Twenty New Zealand White rabbits
      weighing 2.3-3.2 kg were used. In group I (n = 10) a 1-cm-long segment of the
      esophagus was excised and the two free edges anastomosed, to mimic the conditions
      found in newborn esophageal atresia. Group II (n = 10) had a segmental esophageal
      resection and end-to-end anastomosis as in group I but the anastomotic site was
      circumferentially covered with lyophilized type I collagen film. The resected
      segments were processed immediately and served as controls for the postoperative
      tissue in each animal. The animals were starved for the first 24 h and water was
      given on the 2nd postoperative day; on the 3rd postoperative day the animals were
      allowed a normal diet. Two rabbits in group II died on the 7th and 8th
      postoperative days because of a fistula. All the rabbits were killed on the 10th
      postoperative day and 4-cm segments of esophagus with the anastomosis at the
      centre were removed. At this time gross leakage was detected in four animals (one
      in group I and three in group II). Each anastomosis was evaluated for bursting
      pressure, collagen content, and histologic appearance. Bursting pressure was
      higher in group I. Collagen (measured as hydroxyproline) levels in anastomotic
      and adjoining 1-cm segments were compared with concentrations in control segments
      resected during operation. In group II animals there was a significant reduction
      in the lowering of hydroxyproline concentrations around the anastomosis.
      Microscopic evaluation revealed no significant differences between the two
      groups. This experiment showed no demonstrable benefit from the use of
      lyophilized collagen in preventing the esophageal anastomotic leakage that occurs
      in repaired esophageal atresia.

PMID- 9010960
TI  - Reduction of hepatic acute phase response after partial hepatectomy in elderly
      patients.
AB  - The hepatic capacity for acute phase protein synthesis after partial hepatectomy
      in the elderly patients was prospectively studied. Forty-one patients who
      consecutively underwent a partial hepatectomy were grouped according to age of
      greater or less than 70 years; 12 were in the older group and 29 in the younger.
      The changes in the levels of serum interleukin-6, alpha 1-antitrypsin, alpha 1
      acid glycoprotein, haptoglobin, and plasma fibrinogen were measured after
      surgery. The postoperative changes in standard liver function tests were also
      measured. The incidence of postoperative infected complications was 25% in the
      older group and 7% in the younger (P = 0.28). Although postoperative levels of
      serum interleukin-6 were similar between the two groups, those of serum alpha 1
      antitrypsin, alpha 1-acid glycoprotein, and haptoglobin were significantly lower
      in the elderly (P < 0.05). Postoperative levels of serum alpha 1-antitrypsin and
      plasma fibrinogen showed an increase of about 30% compared with the preoperative
      values (P < 0.05) in the younger group, but no significant increase in the older.
      Postoperative deterioration of serum albumin levels and hepaplastin test values
      was also significantly more severe in the older group (P < 0.05). We conclude
      that in the older patients, a reduction of acute phase protein synthesis occurs
      after partial hepatectomy as a result of a global deterioration of liver
      function, and may render patients liable to infection.

PMID- 9010961
TI  - A novelty-related sustained elevation of vasopressin plasma levels in young men
      is not associated with an enhanced response of adrenocorticotropic hormone (ACTH)
      to human corticotropin releasing factor (hCRF).
AB  - A comparative study of the effects of intravenously administered corticotropin
      releasing factor (i.e. exogenous CRF), in the absence or presence of simultaneous
      opioid receptor blockade, versus stress (i.e. endogenous CRF) on plasma
      adrenocorticotropic hormone (ACTH), cortisol and vasopressin (AVP) was carried
      out in ten healthy men (mean age 35.6 +/- 9.5 years) using an intra-individual
      repeat setting. Three different stimuli were applied blindly and in random order,
      one per day, in a 3-day experimental block: (1) human (h) CRF; (2) hCRF/naloxone;
      and (3) a combined multifaceted 5-min stress test. A second block, following the
      same protocol, was carried out 12 weeks later. Each experimental day lasted from
      0700 to 1500 hours, with subjects remaining supine throughout. ACTH and cortisol
      levels each responded with significant peaks to all three stimulating conditions
      in both blocks while AVP levels remained unaffected by any of these stimuli.
      Unexpectedly, in five of the ten subjects significantly elevated AVP basal
      concentrations were measured throughout the first block. This phenomenon appeared
      to be age-related, being observed in younger men only (29.6 +/- 5.2 vs 41.6 +/-
      9.2 years; p = 0.03) and was not paralleled by changes in plasma osmolality or
      blood pressure. In the second block, AVP levels were low and no longer different
      between younger and older subjects. ACTH and cortisol curves did not differ among
      subgroups nor between blocks. In conclusion, plasma AVP, in contrast to ACTH, is
      not acutely influenced by either endogenous or exogenous CRF. However,
      anticipation of novelty seems to be a human-specific, stress-related stimulus for
      a sustained elevation of plasma AVP in young men. This novelty-related continuous
      elevation of AVP levels reported here neither affected basal plasma ACTH nor
      acted synergistically with exogenous hCRF to increase circulating ACTH.

PMID- 9010962
TI  - Modulatory effect of roxithromycin on human neutrophil function.
AB  - Neutrophils are thought to play a key role in tissue injury. We investigated the
      effect of roxithromycin, a 14-membered ring macrolide, on human neutrophil
      functions. The drug inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)
      induced superoxide (O2-) production and Ca2+ influx of human neutrophils. The
      inhibition was overcome by adding an inhibitor of cyclic AMP-dependent protein
      kinase (PKA), H-89. These results suggest that the drug affects O2- production
      and intracellular Ca2+ concentration of neutrophils via the action of PKA.
      Moreover, roxithromycin ameliorated endothelial cell injury induced by
      neutrophils, which may be, in part, due to the effect of the drug on neutrophils.
      Thus, roxithromycin may contribute to the treatment of diseases worsened by the
      excessive action of neutrophils.

PMID- 9010963
TI  - Endotoxin priming exacerbates acute reflux pancreatitis in the rat.
AB  - Recently, endotoxaemia has been reported as a prognostic marker in acute
      pancreatitis. However, the role of endotoxin in inducing or aggravating acute
      pancreatitis is not fully understood. We administered endotoxin 400 micrograms/kg
      i.p. to rats 24 h before performing either a closed duodenal loop (group B) or a
      sham operation (group D). Pancreatic damage and overall survival were compared
      with the results obtained in rats not exposed to endotoxin undergoing either
      closed duodenal loop (group A) or sham treatment (group C). In a first set of
      experiments, 24 h after laparotomy blood samples were collected and the animals
      were sacrificed; survival up to 8 days was estimated in a second set of
      experiments. Group B had higher lipase concentrations and more severe tissue
      damage than group C (P < 0.05). A larger number of abscesses was observed in both
      group B and group D as compared to group C (P < 0.05). Survival was significantly
      shorter in group B (P < 0.0001). We conclude that priming with endotoxin worsens
      the extent of pancreatic damage induced by the closed duodenal loop procedure in
      the rat, possibly favouring selective homing of neutrophils to the site of
      inflammation, in similarity to what happens in the Shwartzman phenomenon.

PMID- 9010964
TI  - Effects of fluid resuscitation with recombinant human serum albumin solution on
      maintaining hepatic energy metabolism in hemorrhagic shock rabbits.
AB  - The objective of this study was to examine the effects of volume replacement with
      recombinant human serum albumin (rHSA), which was developed to reduce the
      consumption of human blood derivatives, on maintaining hepatic energy metabolism.
      Hemorrhagic shock with a mean blood pressure of 50 mmHg was induced within 20 min
      and maintained for 60 min by Wiggars' method in rabbits. Fluid resuscitation
      replacing two thirds of the blood withdrawn with plasma-derived 5% human serum
      albumin (pHSA; n = 7) or rHSA (n = 10), or replacing double the volume of blood
      withdrawn with lactated Ringer's solution (n = 7) was completed within 20 min,
      and observed for 120 min. No significant differences were observed in the blood
      pressures, blood gas analyses, blood counts, biochemical parameters (e.g.,
      alanine aminotransferase, lactate dehydrogenase, creatine kinase, blood urea
      nitrogen, creatinine) or blood glucose levels among the three groups. There were
      also no significant differences in the parameters of hepatic energy metabolism
      such as blood pyruvate and lactate levels and their ratios, ketone body
      concentrations and their ratios, and hepatic tissue energy charge levels among
      the experimental groups. It is suggested that volume replacement with rHSA, like
      pHSA, is able to maintain hemodynamics and organ function in hemorrhagic shock,
      particularly hepatic energy metabolism.

PMID- 9010965
TI  - A retrospective analysis of the pathogenesis of rheumatoid arthritis.

PMID- 9010966
TI  - The three groups of polymyositis.

PMID- 9010967
TI  - Rheumatoid arthritis and bronchiectasis. A retrospective study of fourteen cases.
AB  - Since 1928, 288 cases of rheumatoid arthritis and bronchiectasis have been
      reported in the medical literature. The interactions between these two conditions
      and the etiopathogenic mechanisms they involve remain unclear. During a
      retrospective study of 100 rheumatoid arthritis patients and 80 bronchiectasis
      patients, we identified 14 additional patients with both conditions. There were
      10 females and four males (ratio 2.5/1). Bronchiectasis was confirmed either by
      computed tomography of the chest or by bronchography. The respiratory
      manifestations antedated the joint disease in 12 patients, by a mean interval of
      28.5 years. An infectious cause was identified in six cases. Neither the age at
      onset nor the duration of rheumatoid arthritis were influenced by the presence of
      bronchiectasis. Seven patients had 15 extraarticular manifestations suggesting
      potentially severe joint disease. The flares of joint and respiratory symptoms
      were concomitant in six patients. In six patients, the respiratory manifestations
      worsened after onset of the joint disease. Tests for rheumatoid factors were
      positive in 73% of cases. Panhypogammaglobulinemia was found in one case. Ten
      patients underwent lung function tests, which showed evidence of nonspecific
      obstructive disease. Overall, our findings are consistent with previous reports
      in the literature. In patients with predisposing immunogenetic factors,
      bronchiectasis may be involved in the genesis of rheumatoid arthritis.

PMID- 9010968
TI  - Thyroid gland disorders in primary Sjogren's syndrome.
AB  - OBJECTIVES: To evaluate the frequency of thyroid disorders in primary Sjogen's
      syndrome. PATIENTS AND METHODS: 121 consecutive patients meeting Vitali's
      criteria for primary Sjogren's syndrome and 74 with rheumatoid arthritis
      underwent thyroid hormone assays, tests for antimicrosomal and antithyroglobulin
      antibodies, tests for antinuclear antibodies and antibodies to extractable
      nuclear antigens. Antimicrosomal and antithyroglobulin antibodies were also
      assayed in 404 controls. RESULTS: frequencies were calculated separately in males
      and females, and data in females were subjected to statistical analysis. As
      compared with controls, Sjogren's syndrome patients were more likely to have
      antimicrosomal antibodies (9% versus 17.6%, P < 0.05) and both Sjogren's syndrome
      and rheumatoid arthritis patients were more likely to have antithyroglobulin
      antibodies (1% versus 13.4% and 10.9%, respectively, P < 0.0001). Hypothyroidism
      was more common among Sjogren's syndrome patients (13.4%) than rheumatoid
      arthritis patients (3.1%) (P < 0.05). Sjogren's syndrome patients with thyroid
      disorders were less likely to have antinuclear antibodies, rheumatoid factors or
      a Chisholm's stage 3 or 4 lip biopsy. CONCLUSIONS: our data confirm that thyroid
      disorders are more common in primary Sjogren's syndrome than in rheumatoid
      arthritis and controls. Production of autoantibodies and severe histologic
      lesions were less common in Sjogren's syndrome patients with than without thyroid
      disorders.

PMID- 9010970
TI  - The initial site of bone lesions in Paget's disease. A review of two hundred
      cases.
AB  - We retrospectively evaluated the initial site of bone lesions in 200 patients
      with Paget's disease. There were 117 males and 83 females. Mean follow-up was 13
      years in 98 patients. The initial site can be determined accurately only if less
      than one third of the bone is involved. Paget's disease usually begins in the
      cancellous bone of an epiphysis or metaphysis. A diaphysis is the first site
      involved in some instances, and the anterior subperiosteal area of the proximal
      half of the tibia in a very small number of cases. The distribution of initial
      pagetic lesions in our series is reported for each of the main bones. Lesions
      usually arose in the proximal ends of long bones, which are richly vascularized
      but contain no hematopoietic marrow in adults. This suggests that the
      distribution of pagetic lesions may be more closely dependent on local
      circulatory conditions than on the presence of hematopoietic marrow, which is,
      however, the only source of osteoclasts.

PMID- 9010971
TI  - Methods used to develop clinical guidelines in France. The example of common
      lumbosciatic syndrome.
AB  - A number of Regulatory Medical References, or criteria for quality health care,
      have been worked out in France by a committee of physicians' union and national
      health insurance agency representatives, based on clinical guidelines developed
      using predefined methods. For each guideline, the level of evidence was
      evaluated, and when this level was inadequate a strong professional consensus was
      sought. For common lumbosciatic syndrome, the ANDEM (Agence Nationale pour le
      Developpment de l'Evaluation Medicale, or national agency for the development of
      medical evaluation) worked with a multidisciplinary study group (specialists and
      nonspecialists, physicians from teaching hospitals, regional hospitals and
      private practices, primary care practitioners and specialists) whose members were
      from different areas of France. A computerized and manual literature search was
      conducted. The project director and the study group chairperson reviewed each
      document using predefined criteria to evaluate the methodology and level of
      scientific evidence. When this level was inadequate, a strong consensus
      expressing an opinion accepted by the medical profession was looked for. Bold
      type was used to indicate data resting on very high levels of evidence. The
      committee of physicians' union and national health insurance agency
      representatives used these documents to select a number of situations for which
      "regulatory medical references" would be useful. Each reference was written as
      one or a few sentences starting by "It is inappropriate to...". The study group
      found that subjectivity and pragmatism significantly influence the selection of
      diagnostic and therapeutic strategies for common lumbosciatic syndrome. The
      review and discussion of the high-quality literature on this condition led the
      study group members to modify their opinions and facilitated the development of a
      consensus. The group noted the paucity of scientific data on the natural history
      of common lumbosciatic syndrome and on the value of drug therapy and other
      commonly used therapeutic modalities.

PMID- 9010969
TI  - Spondylarthropathic diseases in indigenous circumpolar populations of Russia and
      Alaska.
AB  - AIMS: To compare the nature and frequency of spondylarthropathy in geographically
      separated but genetically related populations with a high prevalence of HLA-B27.
      METHODS: Using a common questionnaire and disease criteria, cases were
      ascertained through cross-sectional community surveys in Russia and by
      examination and study of possible cases identified through rheumatic disease
      registries and the Native Health Service's computerized patient care data system
      in Alaska. RESULTS: Similar overall prevalences of spondyloarthropathy (2.0-3.4%)
      and a similar spectrum of disease were found, including reactive arthritis,
      ankylosing spondylitis and undifferentiated spondylarthropathy. Psoriatic
      arthritis was very rare. CONCLUSION: No predisposition to one particular form of
      spondyloarthropathy was observed; genetic and microbial settings for a spectrum
      of disease were present. Among adults positive for the presence of HLA-B27 the
      prevalence of all types of spondylarthropathies was estimated to be 4.5%, all
      populations combined, and the prevalence of AS was estimated to be 1.6%.

PMID- 9010972
TI  - Magnetic resonance imaging of the spine in plasma cell dyscrasias. A review.
AB  - This review of recent data on the techniques and results of spinal magnetic
      resonance imaging in plasma cell dyscrasias provides a basis for selecting those
      patients who are most likely to benefit from this investigation. Sagittal images
      should be obtained using T1-weighted spin-echo and T2-weighted gradient-echo
      sequences. Epiduritis is best detected on sagittal or axial images acquired after
      gadolinium injection using T1-weighted spin-echo or phase-opposed gradient-echo
      sequences. Among patients with symptomatic multiple myeloma, 80% have abnormal
      magnetic resonance images of the lower spine due to plasma cell infiltration and
      this proportion increases with the stage in the Durie and Salmon staging system.
      Bone marrow signal abnormalities can be focal, diffuse and homogeneous, or
      diffuse and variegated. Vertebral fractures due to spinal infiltration or
      osteoporosis are seen in 48% of cases and spinal canal narrowing with impingement
      of bone tumors or epiduritis on nervous structures in 20%. The response to
      chemotherapy as evaluated based on conventional criteria is fairly well
      correlated with changes in magnetic resonance imaging findings. Among
      asymptomatic multiple myeloma patients with normal roentgenograms, 50% have tumor
      related abnormalities on magnetic resonance images of the lower spine, which are
      associated with an increased likelihood of rapid progression to symptomatic
      disease. Similarly, one third of patients with an apparently solitary
      plasmacytoma of bone have evidence of other plasma cell tumors on magnetic
      resonance images of the lower spine, and this finding is associated with
      persistence of monoclonal component production after irradiation therapy, which
      may be of adverse prognostic significance. Patients with monoclonal gammopathies
      of uncertain significance have no evidence of tumorous lesions on magnetic
      resonance images of the lower spine.

PMID- 9010973
TI  - Parvovirus B19 infection and rheumatic diseases.
AB  - We reviewed the literature on relationships between human parvovirus B19
      infection and rheumatic diseases. Parvovirus B19 causes erythema infectiosum in
      childhood, transient anemia in immunocompetent individuals, and potentially
      severe infections in fetuses; laboratory evidence that the virus is directly
      responsible for these disorders has been obtained. Acute arthropathy meeting
      American College of Rheumatology criteria for rheumatoid arthritis and disorders
      meeting some of the classification criteria for systemic lupus erythematosus are
      the most striking rheumatic manifestations of parvovirus B19 infection. Purpuric
      lesions have also been reported. Parvovirus B19 infection may be capable of
      inducing a number of manifestations that have not yet been described in the
      literature. Although the relationship between human parvovirus B19 infection and
      rheumatic diseases has been the focus of many studies, compelling evidence that
      the virus is directly involved in the pathogenesis of rheumatic diseases has not
      yet been obtained.

PMID- 9010974
TI  - Rheumatic manifestations due to human parvovirus B19. A report of four cases.
AB  - Human parvovirus B19 has been incriminated in the genesis of hematologic,
      dermatologic, neurologic, and rheumatic disorders. We report four cases in which
      inflammatory rheumatic manifestations developed during the course of human
      parvovirus B19 infection documented by the presence of IgM and IgG antibodies.
      There was one case each of monoarthritis, oligoarthritis, polyarthritis, and
      enthesitis. Three patients had a favorable outcome under nonsteroidal
      antiinflammatory drug therapy, and one developed reflex sympathetic dystrophy
      syndrome. In patients with inflammatory rheumatic manifestations that do not fit
      any specific diagnosis, a careful family history can provide evidence suggesting
      human parvovirus B19 infection, which should be confirmed by tests for IgM and
      IgG antibodies.

PMID- 9010975
TI  - Subchondral insufficiency fracture of the femoral head.
AB  - We report two cases of subchondral insufficiency fractures of the femoral head.
      Clinical manifestations of this lesion are nonspecific. Radionuclide bone
      scanning demonstrates early hyperactivity. Initial roentgenograms are usually
      normal. Magnetic resonance imaging establishes the diagnosis and rules out other
      conditions.

PMID- 9010976
TI  - Accessory soleus muscle. Two case-reports, with a review of the literature.
AB  - The accessory soleus muscle is a supernumerary leg muscle that is rare and
      usually clinically silent. The best diagnostic strategy is not agreed on. We
      report two cases in which magnetic resonance imaging contributed significantly to
      the diagnosis and to the pretreatment evaluation.

PMID- 9010977
TI  - Scintigraphy using iodine 123-labeled serum amyloid P component in ten patients
      with secondary AA type amyloidosis. A descriptive study.

PMID- 9010978
TI  - Uricemia in hemodialyzed patients.

PMID- 9010979
TI  - Heel pain as the inaugural manifestation of metastatic prostate cancer.

PMID- 9010980
TI  - Antibody to factor VIII in rheumatoid arthritis.

PMID- 9010981
TI  - Always more "setrons": how many do we need?

PMID- 9010982
TI  - The SAMOT supportive care programme in southern Italy.
AB  - Since 1988 a palliative care programme has been in development in Palermo, a
      large town in Southern Italy. The main objective is to provide home palliative
      care in conditions in which no other facility exists to meet the needs and reduce
      the distress of terminal cancer patients. This programme has been implemented and
      extended to other cities and villages in Sicily. A team composed of physicians,
      nurses, social workers and volunteers looks after patients at home. This model
      has been recognized as highly effective. The activities, the problems related to
      the development of such programme, including those concerned with the
      sociocultural environment and the family doctor, the needs of specific hospital
      departments, and the scientific and educational activities, are pointed out.

PMID- 9010983
TI  - Innovative approaches in the treatment of emesis.
AB  - Over the last 15 years, appreciation of the role of dopaminergic (D2) receptors
      and serotonergic (5-HT3) receptors has led to the development of a series of
      highly effective antiemetic agents. However, in spite of the suggestion of
      additional significant receptors (such as the NK-1 receptor and the opiate mu
      receptor), recent innovations in antiemetic treatment have concentrated on
      refinement of schedule, route, and dose. Single-dose regimens and oral
      formulations improve the convenience of antiemetic administration, while
      identification of the minimum effective dose has important economic implications.
      Involvement of experienced supportive care investigators in objective
      determination of utility scores for various supportive care modalities will be
      vital for rational inclusion of supportive care in pharmacoeconomic analysis,
      critical pathways, and clinical guidelines.

PMID- 9010984
TI  - Standard treatment of chemotherapy-induced emesis.
AB  - Major breakthroughs in the treatment of chemotherapy-induced emesis have come
      through the use of selective 5-HT3 receptor antagonists in combination with
      corticosteroids. This combination can be considered standard for most but not all
      commonly used chemotherapeutic agents. Delayed-onset emesis remains a problem,
      particularly for patients receiving high-dose cisplatin. There is debate over the
      value of using selective 5-HT3 receptor antagonists beyond the first 24 h.
      Clinical trials have not settled this uncertainty, although it seems likely that
      they add only modestly to the effect of corticosteroids. For both the acute and
      delayed phases, dopamine receptor antagonists may add to the effectiveness of
      antiemetic therapy. This article outlines a strategy for initial antiemetic
      therapy and the rationale for the recommendations.

PMID- 9010985
TI  - Personalized surgery for rectal tumours: the patient's opinion counts.
AB  - In recent times there have been many important changes in the surgical management
      of rectal cancer. The general thrust of these changes has been towards a less
      invasive approach with preservation of intestinal continuity and avoidance of the
      psychological sequelae of a stoma. It is also becoming increasingly apparent that
      profound sexual and autonomic dysfunction can be associated with abdominoperineal
      resection. This paper highlights these issues and the conflict between performing
      an adequate oncological procedure and reducing the incidence of postoperative
      psychological morbidity. It outlines the great changes there have been in
      surgical technique and their relevance to psychological problems after surgery
      for rectal cancer. The need for auditing psychological morbidity when assessing
      the outcome of surgical series is emphasised, as is the importance of involving
      the patient in the medical decision making.

PMID- 9010986
TI  - A double-blind, multicentre comparison of intravenous dolasetron mesilate and
      metoclopramide in the prevention of nausea and vomiting in cancer patients
      receiving high-dose cisplatin chemotherapy.
AB  - The potent serotonin receptor (5-HT3) antagonists are new highly selective agents
      for the prevention and control of chemotherapy-induced nausea and vomiting that
      have been shown to be comparable to or more effective than traditional
      metoclopramide regimens. This study was designed to compare the antiemetic
      efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive
      cancer patients receiving high-dose cisplatin-containing chemotherapy. This
      multicentre, double-blind, randomized trial compared the efficacy and safety of
      single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and
      metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and
      nausea associated with the administration of high-dose (> or = 80 mg/m2)
      cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were
      achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P
      = 0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P = 0.0058 vs
      metoclopramide), and metoclopramide, respectively. Overall, dolasetron was
      significantly more effective than metoclopramide for time to first emetic
      episode, nausea, patient satisfaction, and investigator global assessment of
      efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response
      rates. Dolasetron was well tolerated, with mild-to-moderate headache most
      commonly reported. Twelve percent of patients receiving metoclopramide reported
      extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In
      conclusion, dolasetron mesilate was effective for the prevention of CINV with
      high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective
      than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly
      emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron
      mesilate consistently produced the highest response rates and appears to be the
      most effective dose for further clinical development.

PMID- 9010988
TI  - Dose-finding study of oral metopimazine.
AB  - A few studies indicate a dose-response effect of the antiemetic metopimazine. The
      aim of this study was therefore to investigate the tolerability of increasing
      doses of metopimazine given orally every 4 h for eleven doses. The dose levels 20
      mg, 30 mg, 40 mg, 50 mg and 60 mg were studied in 36 patients completing 46
      cycles of chemotherapy. Serum concentrations of metopimazine and the acid
      metabolite AMPZ were measured by HPLC in 13 patients (15 cycles). The dose
      limiting toxicity was moderate to severe dizziness caused by orthostatic
      hypotension as seen in 0, 0, 17%, 42% and 50% of patients at the respective dose
      levels. Other side effects were few and mild, and only a single possible
      extrapyramidal adverse event was observed in a patient at the 60-mg dose. High
      serum concentrations were not predictive for toxicity, as found on comparison of
      patients with and without symptoms, but in individual patients symptoms were seen
      at the time of Cmax. We found that metopimazine was safe with a dosage of 30 mg x
      6. This dose is four times higher than that previously recommended for antiemetic
      use.

PMID- 9010987
TI  - Efficacy and safety of different doses of granisetron for the prophylaxis of
      cisplatin-induced emesis.
AB  - The purpose of this study was to evaluate the efficacy and safety of four
      different doses of granisetron when administered as a single intravenous (i.v.)
      dose for prophylaxis of cisplatin-induced emesis in a multicenter, randomized,
      parallel-group, double-blind investigation. A total of 353 chemotherapy-naive
      patients were enrolled, stratified according to cisplatin dose (moderate dose: 50
      80 mg/m2, n = 169; high dose: 81-120 mg/m2, n = 184) and randomized to one of
      four granisetron doses: 5, 10, 20, or 40 micrograms/kg. Control of emesis was
      evaluated by the percentages of patients attaining complete response (no vomiting
      or retching, and no rescue medication) and major response (< or = 2 episodes of
      vomiting or retching, and no rescue medication). Patients were assessed on an
      inpatient basis for 18-24 h. Safety analyses consisted of adverse events and
      laboratory parameter changes. Complete response rates over 24 h after
      chemotherapy were 23%, 48%, 48%, and 44% for granisetron doses of 5, 10, 20, and
      40 micrograms/kg, respectively, in the combined patient population (P = 0.011 for
      linear trend); 29%, 56%, 58%, and 41%, respectively, in the moderate-dose
      cisplatin stratum (P = 0.278 for linear trend); and 18%, 41%, 40%, and 47%,
      respectively, in the high-dose cisplatin stratum (P = 0.011 for linear trend).
      Transient headache was the most frequently reported adverse event (19%). There
      was no evidence of association between increased dose and headache. A single 10-,
      20- or 40-micrograms/kg dose of granisetron is comparably effective in
      controlling nausea and vomiting associated with moderate or high-dose cisplatin
      chemotherapy. Granisetron was safe and well tolerated at all doses.

PMID- 9010989
TI  - Fatigue in women treated with bone marrow transplantation for breast cancer: a
      comparison with women with no history of cancer.
AB  - As more individuals undergo autologous bone marrow transplantation (BMT), there
      is growing interest in the impact of treatment side effects on quality of life.
      Fatigue is a potentially disruptive treatment side effect that has not been
      systematically assessed following BMT. The primary aim of this study was to
      determine whether the severity of fatigue and its impact on quality of life is
      significantly greater in women who had undergone BMT for breast cancer than in
      women of similar age with no history of cancer. Another aim was to identify the
      medical and psychosocial correlates of fatigue in women who had completed BMT. A
      group of women treated with autologous BMT for breast cancer (n = 43; mean age =
      44; mean time since BMT = 20 months) and a group of women of similar age with no
      history of cancer (n = 43; mean age = 46) participated in this study. Subjects
      completed measures of fatigue, anxiety, depression, and sleep habits. Medical
      data were obtained from computerized patient records. Women who had completed BMT
      for breast cancer reported significantly more frequent and severe fatigue than
      women with no cancer history. In addition, fatigue had a significantly greater
      impact on daily functioning and quality of life in BMT recipients than in women
      with no cancer history. Fatigue following BMT for breast cancer was related to
      both medical factors (i.e., time since BMT) and psychosocial factors (i.e.,
      anxiety, depressive symptoms and sleep difficulties). Following BMT for breast
      cancer, women may experience fatigue that is worse than might "normally" be
      expected and can interfere with daily functioning and quality of life. Future
      research should focus on identifying the biological correlates of fatigue,
      psychological and physiological mechanisms by which fatigue is produced, and
      interventions to alleviate fatigue.

PMID- 9010990
TI  - Predictors of postbereavement depressive symptomatology among family caregivers
      of cancer patients.
AB  - The present study investigated two aspects of the sequelae of recent bereavement
      among family caregivers following the death of their cancer patient: (1) the
      extent to which depressive symptomatology among family caregivers measured
      following the death of their patient could be predicted by their levels of
      depressive symptomatology in the months prior to death, their physical health,
      the setting in which the patient's death occurred, patient age, gender of the
      caregiver, consanguinity, financial stress, social support from family and
      friends during the terminal stage, impact of caregiving activities on caregiver's
      daily schedule, caregiver optimism, perceived esteem attributed to caregiving,
      the time between the prebereavement assessment and death, and the time between
      death and the postbereavement assessment; and (2) whether these same explanatory
      variables could successfully differentiate those bereaved caregivers whose
      psychological health improved during the first 3 months following bereavement
      from those who did not improve. A sample of 114 family caregivers of cancer
      patients were surveyed for approximately 3 months before and 3 months after the
      death of their patient. A multivariate analysis of variance using the regression
      approach was undertaken to determine the primary predictors of postbereavement
      depressive symptomatology. In addition, a logistic regression analysis was used
      to attempt to predict those caregivers whose depressive symptomatology would
      improve during the postbereavement period. Critical factors in determining levels
      of postbereavement depressive symptomatology were caregiver optimism,
      prebereavement depressive symptomatology, and levels of social support from
      friends. Caregiver optimism and prebereavement depressive symptomatology were
      important in predicting whether caregivers' depressive symptomatology would
      improve or not. Physicians must be aware that if the social history of a patient
      reveals that he/ she is anticipating or has recently experienced the loss of a
      family member for whom they were the primary caregiver, this information may be
      critical in determining whether the illness behavior exhibited by the patient has
      medical or psychosocial origins.

PMID- 9010991
TI  - Palliative iodized talc pleurodesis with instillation via tube thoracostomy.
AB  - Pleural effusions are a severe complication of advanced malignant disease.
      Palliative treatment strategies should be simple and effective. We investigated
      iodized talc pleurodesis through tube thoracostomy for this purpose. A total of
      43 patients received a suspension of 5 g talc with 3 g thymol iodine via chest
      tube. The procedure was well tolerated without major complications in all cases.
      Unfortunately, 4 patients died of disease within the 1st month after treatment,
      so that only 39 patients were evaluable for treatment outcome. Follow-up ranged
      from 1 to 14 months. The success rate after 3 months was 92.5%. In conclusion,
      iodized talc pleurodesis is an excellent tool in the palliative management of
      malignant pleural effusions. Administration via chest tube is sufficient for
      treatment success.

PMID- 9010992
TI  - New approaches to the management and treatment of malignant pericardial effusion.
AB  - The purpose of this study was the evaluation of the effectiveness of
      intrapericardial administration of tetracycline, 5-fluorouracil and cisplatin in
      patients with recurrent malignant pericardial effusion. In 33 cases with
      malignant pericardial effusion 46 pericardiocenteses under two-dimensional echo
      cardiography were performed. No complications were observed after this procedure.
      Pericardiocentesis was followed by catheterization of the pericardial space for a
      mean period of 15 days (range 1-64). In 4 cases bacterial pericarditis was
      observed during catheterization. The mean volume of the pericardial fluid was
      2.41 (range 0.4-13 l). In cases with bloody pericardial fluid the PO2, PCO2 and
      pH of the fluid were estimated and the results compared with the values for
      venous blood obtained from the upper limbs. Highly statistically significant
      differences were documented. Twenty cases of malignant pericardial effusion were
      treated with direct pericardial administration of cisplatin, 3 with 5
      fluorouracil and 2 with tetracycline. Good results (no fluid reaccumulation) were
      observed only after cisplatin therapy. We conclude that pericardiocentesis
      performed under two-dimensional echo cardiography, followed by pericardial
      catheterization and direct pericardial treatment with cisplatin are the methods
      of choice in cases with malignant pericardial effusion. In cases with bloody
      pericardial fluid PO2, PCO2 and pH analysis can be useful to differentiate the
      source of the bloody fluid (blood or bloody fluid).

PMID- 9010993
TI  - Superior vena cava thrombosis secondary to hickman catheter and complete
      resolution after fibrinolytic therapy.
AB  - We present a case of acute-onset vena cava syndrome produced by thrombosis of the
      vena cava superior in a patient receiving adjuvant chemotherapy through a Hickman
      catheter. After angiographic diagnosis fibrinolytic therapy was administered,
      which brought about complete resolution. We also present a brief review of the
      literature.

PMID- 9010994
TI  - Pathogenesis of ruminant herpesvirus infections.
AB  - Ruminants are hosts for members of both Alpha- and Gamma-herpesvirinae. A wide
      range of disease syndromes is associated with infections by these agents. The
      associated diseases reflect the biological nature of the causative viruses.
      Clinically, the symptoms may be mild and localized or include severe generalized
      disease, leading eventually to death. Much knowledge has been gained concerning
      the pathogenesis of some alpha-herpesviruses. Initially, these viruses replicate
      in epithelial cells at the portal of entry. The symptoms of the acute diseases
      are often associated with the destruction of those epithelial cells. However, as
      in the case of bovine herpesvirus 1 (BHV-1), the virus may spread in the infected
      host by viremia, gaining access to a broader range of tissues and organs, and
      causing a broader variety of diseases. Furthermore, many herpesviruses are
      capable of entering neuronal cells. There, they may replicate, which may lead to
      neuronal diseases, for example, encephalitis. In addition, the herpesviruses may
      establish latency in neuronal or lymphoid cells. During latency, apparently no
      viral antigens are synthesized but the genomes of the latent viruses are present
      in the nuclei of long living cells, such as, e.g., neurones of the ganglia
      corresponding to the sites of peripheral replication. Upon reactivation, the
      viruses re-establish the lytic cycle of replication. Shielded from the effectors
      of the immune system, they migrate back to the peripheral tissues where they are
      excreted and may be transmitted. Although a strong immune response is provoked
      during primary viral replication, these mechanisms help the herpesviruses to
      escape from immune surveillance during latency and to a lesser degree during
      reactivation. It has been observed that certain herpesviruses may behave
      differently upon infection of different hosts. Relatively little progress has
      been made concerning the understanding of the pathogenesis of ruminant
      herpesviruses but much has been learned about viral molecular biology. Many viral
      proteins have been identified and characterized and the technology to create
      recombinant viruses has been established. With these tools in our hands, it is
      now possible to address the really interesting questions concerning pathogenesis.
      We postulate that herpesviruses contain at least two sets of genes, a first set
      involved in gene expression and viral replication, and a second set responsible
      for functions, which may affect pathogenesis, latency, and virus/host
      interactions. Using recombinant virus technology, it will be possible in the
      future to design targeted deletions and gene transfers in ruminant herpesviruses
      in order to study the viral and host factors involved in pathogenesis on the
      molecular level.

PMID- 9010995
TI  - Molecular virology of ruminant herpesviruses.
AB  - Molecular virology has served to establish bovine herpesvirus 1 (BHV-1) as the
      prototype member of ruminant herpesviruses. Based on the genomic sequence of the
      virus, we aim to identify and characterize virus-specified components, to explain
      their concerted action, and to predict how the chain of events during the lytic
      and latent phases of the viral life cycle may be interrupted. The nucleotide
      sequence of the BHV-1 genome (136 kb) has just been completed by international
      cooperation (July 1995; except for a small gap in UL36). It comprises 67 unique
      genes and 2 genes, both duplicated, in the inverted repeats. In general, these
      genes exhibit strong homology at the amino acid sequence level to those of other
      alphaherpesviruses (HSV-1, VZV, EHV-1) and are arranged in similar order. A few
      genes are peculiar to only one or two herpesviruses, e.g. in BHV-1 the circ,
      UL0.5, UL3.5 and US1.5 genes. Not long ago, the repertoire of BHV-1 proteins
      under study was restricted to the three major glycoproteins (gB, gC, and gD) and
      thymidine kinase. The repertoire is now growing rapidly and includes 7 additional
      glycoproteins (gE, gI, gH, gL, gG, gK and gM), a number of enzymes (e.g.
      ribonucleotide reductase, DNA Polymerase, dUTPase), and a group of regulatory
      proteins (BICPO, 4, 22, and 27, alpha TIF). Investigations into the functions of
      these proteins and comparison with their counterparts in other herpesviruses
      should reveal which are useful targets for diagnosis, prevention or antiviral
      treatment. Recombinant viruses containing deletions or replacements of individual
      genes are being created, aiming at vaccine development and insights into
      pathogenesis, notably latency, neurotropism, and interference with host
      functions. Molecular analysis of other ruminant herpesviruses is much less
      advanced. Over a dozen virus species have been described; most share basic
      properties with BHV-1 and may be classified as alphaherpesviruses. The
      gammaherpesviruses are represented by the proposed agent of malignant catarrhal
      fever, alcelaphine herpesvirus 1, and by bovine herpesvirus 4, whose partial
      sequences exhibit similarity to herpesvirus saimiri.

PMID- 9010996
TI  - Immunology of bovine herpesvirus 1 infection.
AB  - Immune responses to bovine herpesvirus 1 (BHV-1) have been studied following
      exposure of animals to virulent virus, conventional live or killed vaccines,
      genetically engineered live virus vaccines, subunit vaccines and, more recently,
      following immunization with plasmids encoding putative protective antigens. In
      all cases reported to date, exposure to BHV-1 or its glycoproteins induced
      specific responses to the virus which are capable of neutralizing virus and
      killing virus infected cells. These studies clearly indicate that the responses
      to BHV-1 are broad based, including both Th1 and Th2. In addition to inducing
      neutralizing antibodies, which can prevent virus attachment and penetration,
      these antibodies can also participate in antibody complement lysis of infected
      cells or in antibody dependent cell cytotoxicity. The virus also induces a myriad
      of specific cellular responses including the induction of cytokines, which either
      directly or indirectly inhibit virus replication by activation of effector cells.
      These activities have been associated with lymphocytes, NK-like cells,
      macrophages and polymorphonuclear neutrophils. These effector cells can kill
      virus infected cells either directly or by interacting with antibody to induce
      cell death by antibody dependent cell cytotoxicity. Killing of virus infected
      cells occurs after the expression of viral antigens on the cell surface of
      infected cells. Since the relationship between the time of cell killing and
      completion of virus assembly will influence whether the infectious cycle is
      aborted or results in productive viral replication any enhancement in viral
      killing will dramatically reduce the virus load. Based on these studies, many
      people conclude that antibody is critical in preventing infection and spread to
      susceptible contacts. In contrast, cell mediated immunity is involved in recovery
      from infection. However, none of these events occur in isolation in a body and a
      defect in one will dramatically influence the other. Furthermore, the relative
      importance of each effector mechanism will clearly depend on whether the animal
      is exposed to the virus for the first time (primary infection) or it is a
      secondary exposure following vaccination or infection with the field virus.
      Following a primary infection, where there is no antibody to interfere with the
      initial virus-cell interaction at the receptor level, the virus initiates an
      infection. These initial interactions are mediated primarily by the viral
      glycoproteins. Following the initial infection, viral protein synthesis induces a
      series of events which stimulate the nonspecific immune responses of the host.
      Therefore, the nonspecific immune responses (mediated primarily by viral products
      which induce early cytokines) are amongst the first line of defense in helping
      clear the infection both directly as well as indirectly by stimulating the
      specific immune response. The macrophage is instrumental in focusing the specific
      immune response by producing various cytokines and subsequently responding to
      cytokines produced by T-cells to kill to virus infected cells. This activity is
      detectable within 2 days after infection in lung parenchymal cells and 5-7 days
      in peripheral blood leukocytes. Interactions between various effector functions
      in limiting virus replication are described.

PMID- 9010997
TI  - Advances in the development and evaluation of bovine herpesvirus 1 vaccines.
AB  - This review deals with conventional and modern bovine herpesvirus 1 (BHV1)
      vaccines. Conventional vaccines are widely used to prevent clinical signs of
      infectious bovine rhinotracheitis. The use of conventional vaccines, however,
      does not appear to have resulted in reduction of the prevalence of infection.
      Novel BHV1 marker vaccines comprise either mutants with a deletion in one of the
      non-essential genes, or subunit vaccines that contain one or more glycoproteins.
      These marker vaccines can be used in conjunction with companion diagnostic tests
      to differentiate between infected and vaccinated cattle. Their efficacy has been
      evaluated in vaccination-challenge experiments, transmission experiments and in
      field trials. The results demonstrate that the marker vaccines can contribute to
      the eventual eradication of BHV1. However, there remains room for improvement of
      BHV1 marker vaccines.

PMID- 9010998
TI  - Lessons to be learned from varicella-zoster virus.
AB  - Varicella-zoster virus (VZV) is an alphaherpesvirus responsible for two human
      diseases: chicken pox and shingles. The virus has a respiratory port of entry.
      After two successive viremias, it reaches the skin where it causes typical
      lesions. There, it penetrates the peripheral nervous system and it remains latent
      in dorsal root ganglia. It is still debatable whether VZV persists in neurons or
      in satellite cells. During latency, VZV expresses a limited set of transcripts of
      its immediate early (IE) and early (E) genes but no protein has been detected.
      Mechanisms of reactivation from ganglia have not been identified. However,
      dysfunction of the cellular immune system appears to be involved in this process.
      The cell-associated nature of VZV has made it difficult to identify a temporal
      order of gene expression, but there appears to be a cascade mechanism as for HSV
      1. The lack of high titre cell-free virions or recombination mutants has hindered
      so far the understanding of VZV gene functions. Five genes, ORFs 4, 10, 61, 62,
      and 63 that encode regulatory proteins could be involved in VZV latency. ORF4p
      activates gene promoters with basal activities. ORF10p seems to activate the ORF
      62 promoter. ORF61p has trans-activating and trans-repressing activities. The
      major IE protein ORF62p, a virion component, has DNA-binding and regulatory
      functions, transactivates many VZV promoters and even regulates its own
      expression. ORF63p is a nuclear IE protein of yet unclear regulatory functions,
      abundantly expressed very early in infection. We have established an animal model
      of VZV latency in the rat nervous system, enabling us to study the expression of
      viral mRNA and protein expression during latency, and yielding results similar to
      those found in humans. This model is beginning to shed light on the molecular
      events in VZV persistent infection and on the regulatory mechanisms that maintain
      the virus in a latent stage in nerve cells.

PMID- 9011000
TI  - Bovine herpesvirus 4: genomic organization and relationship with two other
      gammaherpesviruses, Epstein-Barr virus and herpesvirus saimiri.
AB  - Bovine herpesvirus 4 (BHV-4) belongs to the gammaherpesvirinae subfamily.
      Although the whole sequence of BHV-4 genome is not known it was possible, based
      on random sequencing, to assume that its genomic organization consists of genes
      clustered in blocks whose orientation and location in the genome are conserved
      within a herpesvirus subfamily. Between these blocks lie genes which are specific
      to either a particular virus or a virus subfamily. BHV-4 genome consists of 5
      gene blocks conserved among the gammaherpesviruses and particularly within the
      Epstein-Barr virus (EBV) and the herpesvirus saimiri (HVS) genomes. Analysis of
      the regions located outside the gene blocks showed the presence of 12 open
      reading frames (ORFs). Protein database comparisons showed that no ORF
      translation products were similar to proteins encoded by alpha- or beta
      herpesviruses. Nevertheless, 5 ORFs were homologous in amino acid sequences to
      proteins encoded by HVS and one was similar to a protein encoded by both HVS and
      EBV. On the basis of the molecular data BHV-4 is more closely related to HVS than
      to EBV. Genes homologous to cellular genes have been described in both HVS and
      EBV genomes. No genes homologous to presently sequenced cellular genes were found
      among those found in the BHV-4 genome to date.

PMID- 9010999
TI  - Gene contents in a 31-kb segment at the left genome end of bovine herpesvirus-1.
AB  - We report the nucleotide sequence of a 31-kb segment at the left genome end of
      bovine herpesvirus-1 (BHV-1) and show that it comprises 19 different open reading
      frames (ORFs), including seven which have been described previously (circ,
      dUTPase, UL49.5, alpha TIF, VP8, glycoprotein C, and ribonucleotide reductase
      small subunit). The new sequence resulted in a correction at the C-terminus of
      glycoprotein C. All 19 ORFs exhibited strong amino acid sequence homology to the
      gene products of other alphaherpesviruses. The BHV-1 ORFs were arranged
      colinearly with the prototype sequence of herpes simplex virus 1 (HSV-1) in the
      range of the UL54 to UL37 genes. No BHV-1 homologs of the HSV-1 UL56, UL55, and
      UL45 genes were identified. The BHV-1 circ gene was the only gene without a HSV-1
      counterpart. The additional ORFs 1 and 2 found at the left genome end of equine
      herpesvirus-1 (EHV-1) were absent in BHV-1. Among the newly sequenced BHV-1 ORFs
      are homologs of ICP27 (UL54), glycoprotein K (UL53), helicase-primase (UL52), DNA
      polymerase accessory protein (UL42), ribonucleotide reductase large subunit
      (UL39), and several virion proteins (UL49, UL46, UL43, UL41, UL38, UL37), most of
      which are strongly conserved in all herpesviruses. The possible functions of the
      proteins encoded within the sequenced region are assessed and features found are
      discussed.

PMID- 9011001
TI  - Structural and functional analysis of bovine herpesvirus 1 minor glycoproteins.
AB  - This paper focuses on the structure and functions of bovine herpesvirus 1 minor
      glycoproteins gH, gE, gG and gp42. It reviews the progress which has been made in
      their identification and characterization, in the study of their temporal
      expression and processing in infected cells, and finally in the understanding of
      their biological activities. In addition, aspects discussed include a comparison
      with two other alphaherpesviruses, namely herpes simplex virus and pseudorabies
      virus.

PMID- 9011002
TI  - Persistence of antibodies against bovine herpesvirus 1 and virus reactivation two
      to three years after infection.
AB  - To study the long-term persistence of bovine herpesvirus 1 (BHV1) specific
      antibodies in cattle, serum samples were collected regularly over a period of two
      to three years after infection. The sera were titrated in a BHV1 neutralizing
      antibody test, a glycoprotein gB blocking ELISA and a glycoprotein gE blocking
      ELISA. Sera collected after infection were positive in all tests and the titres
      declined only minimally during the investigation period. Two to three years after
      infection, four animals were treated with dexamethasone to reactivate putatively
      latent virus. Virus was isolated from the nasal swabs from three animals, and PCR
      analysis proved the presence of BHV1-DNA in the trigeminal ganglia of the fourth
      animal. The results demonstrated that four animals still harboured latent BHV1,
      which was reactivated and excreted in three animals, two to three years after
      infection. Hence, the persistence of antibodies allowed the detection of latently
      infected cattle.

PMID- 9011003
TI  - Characterisation of the lymphoproliferation in rabbits experimentally affected
      with malignant catarrhal fever.
AB  - Malignant catarrhal fever (MCF) in rabbits caused by the three Herpesviruses:
      alcelaphine herpesvirus-1 (AHV-1), ovine herpesvirus-2 (OHV-2) and hippotragine
      herpesvirus-1 (HipHV-1) induced hyperplasia of lymphoid tissues and accumulations
      of mononuclear lymphoid cells in non-lymphoid tissues. However, certain lymph
      nodes were affected preferentially. The lymphoid cells in non-lymphoid tissues
      were CD43+ T-cells which showed evidence of in situ multiplication. A more
      detailed phenotypic analysis of splenocytes and lymph node cells in AHV-1
      infected rabbits suggested that the hyperplasia was probably due to the expansion
      of CD8+ T-cells. On the basis of these data and the observations of other
      authors, that no or very little viral expression can be detected in lesions of
      MCF affected animals, we propose that the pathogenesis of MCF results from a
      dysregulation of a secretory T-cell activator. The variable pathology induced by
      the three viruses may reflect a quantitative or qualitative differences in this
      proposed activator.

PMID- 9011004
TI  - The role of glycoproteins gC, gE, gI, and gG in the induction of cell-mediated
      immune responses to bovine herpesvirus 1.
AB  - Mutant viruses with deletions in genes encoding non-essential glycoproteins are
      considered as promising bovine herpesvirus 1 (BHV1) vaccine candidates. The
      present study compared the influence of various gene deletions (gC, gE, gI, gG)
      on the induction of cell-mediated immune responses against the virus. The highest
      BHV1 specific lymphoproliferative response was observed in the group of calves
      inoculated with the gC- mutant. However, in all groups of inoculated calves,
      limiting dilution analysis showed marked individual variability in the number of
      BHV1 specific T lymphocytes that were stimulated. The same animals were then
      challenged with wild-type BHV1. In these animals, limiting dilution analysis did
      not reveal gE, gI nor gG as a major T lymphocyte antigen. However, further
      analysis suggested the T cell antigenicity of gE in a low number of BHV1
      hyperimmunized calves. Stimulation of MHC unrestricted cytotoxicity was also
      evaluated after inoculation with the various deletion mutants. Cytotoxicity in gC
      inoculated calves was as high as in BHV1 inoculated calves. In conclusion, among
      the BHV1 deletion mutants that were tested, the gC- mutant stimulated the best
      cell-mediated immune responses.

PMID- 9011005
TI  - Assessment of the cell-mediated immunity in cattle infection after bovine
      herpesvirus 4 infection, using an in vitro antigen-specific interferon-gamma
      assay.
AB  - The cell-mediated immunity (CMI) following bovine herpesvirus 4 (BHV4) infection
      has been poorly investigated in cattle. The in vivo response measured by a
      delayed type of hypersensitivity (DTH) assay has been reported to be positive in
      only few animals showing serological evidences of BHV4 infection. We have
      investigated the CMI following BHV4 infection by an in vitro antigen-specific
      interferon gamma (IFN-gamma) release assay, as an indicator of an actively
      acquired immunity to BHV4. Our preliminary results using a partially purified
      antigen suggest that there was a measurable CMI in 75 out of 168 animals (44.4%)
      originating from a farm with a clinical history and serological evidences (76.3%
      seropositivity) of BHV4 infection. If the results of serological tests and BHV4
      IFN-gamma test are interpreted in parallel, 81.5% of the animals are classified
      positive, demonstrating the complementarity of these tests. The specificity of
      the BHV4 IFN-gamma test was supported by the absence of a measurable CMI in 41
      animals originating from a farm with no clinical history or serological evidence
      of BHV4 infection. In an allied study, we developed a bovine herpesvirus 1 (BHV1)
      IFN-gamma test. This allowed us to measure the antigen specific IFN-gamma release
      after stimulation with a mixture of BHV1 and BHV4 antigens. Animals that were
      classified negative by the BHV4 IFN-gamma test and by the BHV1 IFN-gamma test,
      were classified negative after stimulation with a mixture of both antigens.
      Animals that were classified positive by the BHV4 IFN-gamma test or the BHV1 IFN
      gamma test, were classified positive after stimulation with a mixture of both
      antigens. Taken together these results suggest that the in vitro assessment of
      the CMI after BHV4 infection should be further investigated as a specific and
      valuable alternative to the DTH assay.

PMID- 9011006
TI  - Antibody isotype responses to experimental infection with bovine herpesvirus 1 in
      calves with colostrally derived antibody.
AB  - Calves, both positive and negative for maternal antibody to bovine herpesvirus 1
      (BHV-1), were infected with BHV-1 and their serum antibody isotype responses were
      measured post-infection. In the case of maternal antibody negative calves there
      was a classical humoral response to the virus with an early IgM peak followed by
      IgG1 and IgG2 responses. In maternal antibody positive calves, although infection
      was established, no active antibody response was detected in serum except for a
      transient IgM peak in a single calf. By contrast, a delayed-type hypersensitivity
      test response could be elicited in both groups of calves by intradermal
      inoculation of nucleocapsid antigen at 4.5 months after the initial infection.
      The intradermal antigen also stimulated an antibody response. In calves with high
      levels of maternal antibody at the start of the experiment, and which were not
      subsequently infected, maternal antibody waned to negative levels by seven months
      of age. They were skin test negative and did not show a serological response to
      skin test antigen. It was concluded that isotype specific serology could not be
      used to distinguish calves with passive immunity to BHV-1 from those with active
      immunity and putative latent infection. Although the skin test had potential to
      provide such a distinction, it could compromise future serological monitoring of
      the animals.

PMID- 9011007
TI  - A European inter-laboratory trial to evaluate the reliability of serological
      diagnosis of bovine herpesvirus 1 infections.
AB  - The detection of cattle latently infected with bovine herpesvirus 1 (BHV1) is of
      importance in control programs and in international trade activities. Therefore,
      tests to detect specific antibodies in serum must be highly sensitive. To
      evaluate the reliability of serological diagnosis of BHV1 infections in Europe,
      seventeen laboratories in 15 European countries were asked to determine BHV1
      specific antibodies in a panel of bovine serum samples using the serological
      tests available in their laboratory. Laboratory tests included virus
      neutralisation tests (1, 2 and 24 h), indirect immunofluorescence tests and
      ELISAs. The serum panel consisted of 12 duplicate lyophilised samples which were
      randomly coded from 1 to 24 and included negative, weak- and strong-positive
      samples as well as international reference sera. Virus neutralisation tests and
      ELISAs showed a high specificity. All participants using neutralisation tests (n
      = 13) scored the negative samples correctly. Twenty three of 25 ELISAs showed
      100% specificity. A serum sample obtained at day 7 after infection was scored as
      negative by all tests except one home-made blocking ELISA. Samples obtained at
      day 9 and at day 11 after infection were scored as positive by approximately half
      and by all tests, respectively. To score the weak-positive European reference
      standard (EU2) correctly, 24 h neutralisation tests (positive by 8 of 9
      laboratories) and home-made blocking ELISAs (positive by 5 of 6 laboratories)
      were the most reliable. The results indicate that standardisation is urgently
      needed to ensure that BHV1-infected animals with low antibody titres are
      recognised.

PMID- 9011008
TI  - The use of a polymerase chain reaction assay for the detection of bovine
      herpesvirus 1 in semen during a natural outbreak of infectious bovine
      rhinotracheitis.
AB  - Nasal swabs from two bulls at an artificial insemination (AI) station were
      submitted to our laboratory. The animals showed clinical signs of Infectious
      bovine rhinotracheitis (IBR), although the station was supposedly free of bovine
      herpesvirus 1 (BHV1). DNA of BHV1 was detected using a polymerase chain reaction
      (PCR). Subsequently nasal swabs from 100 animals that could have been in contact
      were submitted. BHV1 DNA was detected in swabs from 23 animals. Using the PCR,
      BHV1 could only be detected in a limited number of semen samples over a period of
      two months prior to the outbreak or two months after the outbreak. Also, not all
      animals that shed BHV1 from the nose harboured detectable BHV1 in the semen.
      Finally BHV1 was detected in the semen of one bull, approximately six weeks
      before seroconversion. Presently the PCR is being used as a means of quality
      control of fresh semen from bulls that are seropositive for BHV1. We are able to
      produce a result within 6 h after the semen samples have been submitted, allowing
      the AI-station manager to take measures before semen distribution in the event of
      a positive reaction. So far 11 out of 318 samples were shown to contain BHV1 DNA.
      In order to be able to interpret these results an interlaboratory comparative
      study is proposed. In countries endemically infected with BHV1 the PCR can be a
      cost-effective method to minimize the risk of transmitting virus by semen.

PMID- 9011009
TI  - Population dynamics of bovine herpesvirus 1 infection in a dairy herd.
AB  - An induced outbreak of a bovine herpesvirus 1 (BHV1) infection in a dairy herd is
      described. The outbreak was induced by injecting three BHV1 seropositive cows
      with dexamethasone. Within 7 weeks all seronegative cows had seroconverted. Also
      some seropositive animals showed a significant increase in serum antibody titre.
      Using these data, parameters of population dynamics such as R0, the basic
      reproduction ratio, could be estimated. The basic reproduction ratio is a
      threshold value describing infection dynamics in a population. This parameter is
      defined as the average number of secondary cases generated by one primary case in
      a wholly susceptible population of defined density. In this population R0 was
      estimated to be at least 7. The importance of these findings, and implications
      for eradication of BHV1 are discussed.

PMID- 9011010
TI  - A gE deleted infectious bovine rhinotracheitis marker vaccine for use in improved
      bovine herpesvirus 1 control programs.
AB  - Based on a glycoprotein E (gE) deleted bovine herpesvirus 1 (BHV1) strain
      (Kaashoek et al., 1994) a killed virus as well as a modified live virus marker
      vaccine have been developed that allow differentiation between immunized and BHV1
      infected cattle. Safety and efficacy of both vaccines were tested extensively
      following the current European Union (EU) requirements for the development of
      bovine vaccines. The minimum vaccine dose, vaccination regimen, route of
      administration and duration of immunity were evaluated for both vaccines in
      comprehensive vaccination/challenge trials in cattle. The most potent adjuvant
      formulation for the killed virus vaccine was also selected by experimental
      challenge infections. For the modified live virus marker vaccine it could be
      demonstrated that maternally derived BHV1 specific antibodies did not interfere
      with vaccination. Safety could be demonstrated for both the killed virus and the
      modified live virus vaccine in all target animal categories including veal
      calves, beef cattle, bulls, heifers and dairy cattle, including pregnant animals.

PMID- 9011011
TI  - Early immunity induced by a live gE-negative bovine herpesvirus 1 marker vaccine.
AB  - We studied the early immunity induced by a live glycoprotein E (gE) negative
      bovine herpesvirus 1 (BHV1) marker vaccine. Three groups of specific-pathogen
      free calves were either not vaccinated, or vaccinated two days or two hours
      before the introduction of a calf that was intranasally infected with wild-type
      BHV1 the day before. We quantified the shedding of gE-negative vaccine virus and
      of wild-type virus, using a double-staining immunoassay. In calves vaccinated two
      hours before the introduction of the infected calf, the shedding of wild-type
      virus was reduced, compared with that of the unvaccinated control calves. The
      shedding of wild-type virus was most significantly reduced in the calves that
      were vaccinated two days before: only very small amounts of wild-type virus were
      isolated. Wild-type virus was not detected at all in the samples from one of the
      five calves of that group. Furthermore, this calf was the only one in which we
      did not detect antibodies against gE. Hence, intranasal vaccination with a live
      gE-negative vaccine induced early immunity against a BHV1 contact infection. This
      suggests that this vaccine can be used efficaciously in the early stages of a
      BHV1 outbreak.

PMID- 9011012
TI  - Development of a disease control programme based on the use of an inactivated
      vaccine against infectious bovine rhinotracheitis.
AB  - Studies to investigate the efficacy of an inactivated vaccine against infectious
      bovine rhinotracheitis (IBR) suggest that this vaccine can prevent the in utero
      infection of calves from experimentally infected dams. In an experimental herd
      the inactivated vaccine induced a humoral immune response in both seropositive
      and seronegative cattle and, after subsequent intratracheal infection with IBR
      (BHV-1) virus, prevented development of symptoms in the cows and protected their
      fetuses against infection. The calves were all healthy and were born at term. The
      non-vaccinated, seronegative cows responded to the experimental infection with
      mild respiratory disease and abortion of 4 out of 10 fetuses. All organs from the
      aborted fetuses were found to have IBR virus. Through the use of this vaccine,
      the nucleus of a seronegative, virus-free breeding herd can be established. Thus,
      valuable genetic material can be preserved and the eradication of IBR becomes a
      realistic prospect. From our initially strictly controlled experiments producing
      234 healthy calves, our programme was expanded into farm practice where 1001
      calves were reared free from IBR virus.

PMID- 9011013
TI  - Conclusions from the symposium.

PMID- 9011014
TI  - A review of Neospora caninum and neosporosis.
AB  - Neospora caninum is a recently recognized protozoan parasite of animals, which
      until 1988 was misidentified as Toxoplasma gondii. Its life cycle is unknown.
      Transplacental transmission is the only recognized mode of transmission. It has a
      wide host range, but its zoonotic potential is unknown. Neosporosis is a major
      cause of abortion in cattle in many countries. It is also an important cause of
      neuromuscular paralysis in dogs. This paper reviews information on parasite
      structure, life cycle, biology, clinical signs, diagnosis, treatment and control.

PMID- 9011015
TI  - Effect of Toxoplasma gondii infection on the development of pregnancy and on
      endocrine foetal-placental function in the goat.
AB  - The effect of Toxoplasma gondii inoculation on pregnancy and on endocrine foetal
      placental function in pregnant goats was studied. Five susceptible goats were
      inoculated subcutaneously with T. gondii bradyzoites at 71 +/- 2 days of
      gestation. Another five goats were used as controls. Plasma was analysed for
      progesterone, oestrone sulphate and 15-ketodihydro-PGF2 alpha. The condition of
      the foetuses was monitored by real-time ultrasonography. All inoculated goats
      aborted or delivered stillborn or weak kids 54-73 days after inoculation. None of
      the goats showed signs of general disease. In cases of foetal death, the
      ultrasound examination revealed that death occurred between day 1 and 12 before
      abortion or birth. The appearance of the foetuses varied from fresh to mummified,
      depending on the number of days between foetal death and expulsion. All five
      goats became serologically positive to T. gondii after inoculation. None of the
      goats used as controls aborted, but one goat delivered one mummified and one weak
      kid for unknown reasons. In inoculated animals an increase in 15-ketodihydro-PGF2
      alpha levels in plasma and a subsequent tendency to a decrease in oestrone
      sulphate levels were observed from about day 40 after inoculation and until
      abortion or birth. High levels of 15-ketodihydro-PGF2 alpha were seen after
      foetal death. High levels of 15-ketodihydro-PGF2 alpha were not always followed
      by a drop in progesterone levels. The mean level of progesterone was slightly
      decreased after inoculation and onwards. The pattern of progesterone levels
      around abortion in the inoculated goats was very similar to the pattern around
      parturition in the control goats. However, 15-ketodihydro-PGF2 alpha levels were
      higher both before and after abortion in inoculated goats than in control goats.
      The level of oestrone sulphate did not increase in the inoculated group before
      abortion in contrast to the level in goats which delivered healthy kids. The
      patterns of changes in levels of 15-ketodihydro-PGF2 alpha and oestrone sulphate
      in inoculated animals indicate that the endocrine foetal-placental function was
      disturbed in most of the inoculated goats, probably due to the injury caused by
      the establishment and development of T. gondii infection in the placenta and
      foetus.

PMID- 9011016
TI  - Comparison of an acid-fast stain and a monoclonal antibody-based
      immunofluorescence reagent for the detection of Cryptosporidium oocysts in faecal
      specimens from cattle and pigs.
AB  - A commercially available direct immunofluorescence (IF) assay with monoclonal
      antibodies (Monofluo Kit Cryptosporidium, Diagnostics Pasteur, France) was
      compared with the modified Ziehl-Neelsen (MZN) acid-fast technique for the
      detection of Cryptosporidium oocysts in faecal samples from cattle and pigs.
      Stool specimens individually collected from 108 bovines and 90 pigs were examined
      in a blind test. The results of the two procedures corresponded (both positive or
      negative) in 102 (94.4%) cattle samples and 80 (88.9%) pig faecal samples.
      However, the remaining six (5.5%) cattle specimens and 10 (11.1%) pig stool
      samples, all of them harboring few oocysts (0-1 oocysts per 20 x field), were
      negative by MZN and positive by IF. False-negative results of the acid-fast stain
      occurred in suckling (17.2% of discrepant results) and weaned calves (2.9%) as
      well as weaned piglets (43.7%) and fattening pigs (10%). Stool specimens from the
      remaining age groups were negative by both techniques. The MacNemar's chi-square
      test showed that differences between both methods were statistically significant
      (P < 0.05). Compared with immunofluorescence procedure, the sensitivity of MZN
      technique in samples from cattle and pigs was 79.3% and 67.7% and the negative
      predictive value was 92.9% and 85.5% respectively. The specificity and positive
      predictive values of the acid-fast stain were 100% in both animal species. It is
      concluded that the monoclonal antibody-based immunofluorescence reagent evaluated
      is more efficient that the MZN technique, especially for detecting a low number
      of Cryptosporidium oocysts, in faecal specimens from both cattle and pigs.

PMID- 9011017
TI  - Prevalence of Cryptosporidium infections in pigs in Aragon (northeastern Spain).
AB  - Faecal samples from 620 pigs randomly selected from 27 farms throughout Aragon
      were examined to determine the prevalence of Cryptosporidium infections.
      Detection of oocysts was performed using the ethyl-acetate stool concentration
      method and the modified Ziehl-Neelsen technique. Cryptosporidium parvum oocysts
      were identified in 136 (21.9%) pigs from 21 (77.8%) farms. Infected animals
      ranged from 1 to 6 months old and oocysts were not detected in suckling piglets
      or adults. Infection rates were significantly higher in weaned, 1-2 month old
      piglets (59.2%) than in fattening, 2-6 month old pigs (34.3%) (P < 0.001).
      Cryptosporidial infections were asymptomatic in most of the pigs (90.4%) and
      usually of low intensity, since 92.6% of the infected pigs excreted few oocysts
      (0-1 oocysts per field at x 200 magnifications). Although 24.1% of weaned and
      5.6% of fattening pigs infected by C. parvum had diarrhoea, it was not found to
      be statistically associated with infection. In fact, infection rates were higher
      in non-diarrhoeic than in diarrhoeic pigs, in both weaned (64.7% and 46.7%,
      respectively) and fattening pigs (34.3% and 33.3%).

PMID- 9011018
TI  - Experiments on the transmission of Babesia major and Babesia bigemina by
      Haemaphysalis punctata.
AB  - Experiments on the transmission by Haemaphysalis punctata of three large Babesia
      strains were carried out. Three Babesia-free batches of laboratory reared H.
      punctata ticks were infected with two strains of Babesia major, B. major
      (Xingjiang strain), isolated with adult ticks of H punctata and B. major (Henan
      strain), isolated with H. longicornis) and a strain of Babesia bigemina by
      feeding them on the calves infected by inoculation of blood stabilates. H.
      punctata was shown to be capable of transmitting the B. major strains
      transovarially. The larvae, nymphs and adults developed from female ticks
      engorged on the calf infected with B. major (Xingjiang strain) transmitted the
      pathogen to splenectomised calves with prepatent periods of 15, 11 and 12 days,
      respectively. The calves infested with larvae and nymphs died of babesiosis with
      parasitemias of 400 and 710 per 1000 erythrocytes. The calf infested with adult
      ticks survived babesiosis, but the number of erythrocytes and the amount of
      haemoglobin were reduced greatly. H. punctata transmitted B. major (Henan strain)
      in the same way. The prepatent periods of the calves infested with larvae, nymph
      and adult ticks were 9, 10 and 12 days, respectively. Calves infested with larvae
      survived, but those infested with nymphal and adult ticks died of babesiosis with
      parasitemias of 410 and 100 per 1000 erythrocytes, respectively. H. punctata
      ticks did not transmit the B. bigemina strain to splenectomised calves. There
      were no clinical symptoms and no parasites were discovered in the blood films
      during a 2 month observation period after the calves were infested with larval,
      nymphal and adult ticks derived from female ticks engorged on calves inoculated
      with B. bigemina.

PMID- 9011019
TI  - Comparison of indirect immunofluorescent antibody test and modified direct
      agglutination test methods for detection of Toxoplasma gondii antibodies in adult
      sheep in Spain.
AB  - A total of 2306 serum samples obtained from adult sheep were analysed for
      Toxoplasma gondii IgG antibodies by modified direct agglutination test and
      indirect immunofluorescence assay test. Similar results were obtained with both
      procedures (seroprevalence of 35.27% for modified direct agglutination test and
      33.72% for indirect immunofluorescence assay test at dilution 1:80), but some
      differences in relation to sample dilution were registered. All the titers
      assayed (dilution two-fold from 1:40 to 1:320) can be used in diagnosis with both
      procedures, but titers 1:80 are recommended for screening studies in ovine
      flocks.

PMID- 9011020
TI  - The epidemiology of gastrointestinal nematode infections in communal cattle and
      commercial beef cattle on the highveld of Zimbabwe.
AB  - An epidemiological study of gastrointestinal nematode infections of cattle was
      conducted on the highveld of Zimbabwe from June 1993 to May 1995. The study was
      carried out in two communal areas, two conventional beef farms and two commercial
      beef farms with irrigated pastures. On all farms/areas, faecal egg counts were
      low (< 500 eggs per g faeces) during the dry season. During the rainy season
      faecal egg counts were highest in communal areas and lowest in conventional beef
      farms. Those of irrigated farms had intermediate values. During the dry season
      pasture larval counts were low in irrigated pastures and conventional beef farms
      and virtually zero in communal areas. They increased and peaked during the rainy
      season, coinciding with the egg count peaks. Worm burdens of necropsied cattle
      indicated that 100% of the animals were infected with nematodes. The important
      species were Cooperia pectinata, C. punctata, Haemonchus placei, Trichostrongylus
      axei and Oesophagostomum radiatum in all farms/areas and Ostertagia ostertagi in
      a beef farm with irrigated pastures. Haemonchus survived the dry season as
      inhibited early fourth stage larvae whereas Cooperia and Trichostrongylus
      survived as adults.

PMID- 9011021
TI  - Immunisation of sheep by drug-abbreviated infections of Ostertagia circumcincta
      and Trichostrongylus colubriformis against field challenge of gastro-intestinal
      nematodes.
AB  - A very high level of protection was achieved against homologous (up to 97%) and
      heterologous (up to 87%) infections in 12-month-old Romney sheep immunised with
      oxfendazole-abbreviated infections of Ostertagia circumcincta and
      Trichostrongylus colubriformis. No significant protection occurred following
      ivermectin-abbreviated infections. None of the immunised sheep showed an increase
      in antibody level against excretory-secretory antigen of T. colubriformis
      infective larvae. The immunisation procedures did not cause a decrease in wool
      production, or liveweight gains compared with non-immunised controls.

PMID- 9011022
TI  - A molecular switch for biochemical logic gates: conformational studies.
AB  - This report presents the computer-assisted design of a molecular switching
      element, in which a molecular switch regulates the enzymatic activity of
      Ribonuclease A (RNase A). The molecular switch, an appropriately modified amino
      acid residue, is constructed with an electron donor group and an electron
      acceptor group, connected to one another with a conjugated double bond bridge.
      The switching mechanism is based on the azonium-hydrazo tautomerization, by which
      a charge separation induced in the excited state causes a rearrangement of the
      molecular electronic structure, resulting in the exchange of locations of single
      and double bonds. This rearrangement of bonds leads to different three
      dimensional conformations of the switch. Using the electrostatically driven Monte
      Carlo (EDMC) method and the empirical conformational energy program for peptides
      (ECEPP/3) potential energy function, we carried out an exhaustive search of the
      conformational space of the switching element. The results of these calculations
      reveal two sets of conformations: in one set the access to the active site of the
      enzyme is preferentially blocked, while in the other set the active site is
      preferentially accessible. Integration of the designed element into biochemical
      logic gates operating under the rules of threshold value, and experimental
      implementation of this system, are considered.

PMID- 9011023
TI  - Evaluation of a fiber optic immunosensor for quantitating cocaine in coca leaf
      extracts.
AB  - A fiber optic evanescent fluoroimmunosensor was used to rapidly detect and
      quantitate coca alkaloids as cocaine equivalents in leaf extracts of five
      Erythroxylum species. A monoclonal antibody (mAb) made against benzoylecgonine
      (BE), a major metabolite of cocaine, was immobilized covalently on quartz fibers
      and used as the biological sensing element in the portable fluorometer.
      Benzoylecgonine-fluorescein (BE-FL) was used as the optical signal generator when
      it bound to the fiber. If present, cocaine competed for the mAb and interfered
      with the binding of BE-FL, thereby reducing the fluorescence transmitted by the
      fiber. Calibration curves were prepared by measuring (over 30 s) the rates of
      fluorescence increase in the absence, or presence of cocaine. Ethanol or acid
      extracts of dry coca leaves were assayed by this fiber optic biosensor, gas
      chromatography and a fluorescent polarization immune assay. Biosensor values of
      cocaine content of leaves from five Erythroxylum species were not significantly
      different from gas chromatography values, but had higher variance. The biosensor
      assay was rapid and did not require cleanup of the crude leaf extracts. Cocaine
      in acid extracts was reduced significantly after 4 weeks at 23 degrees C and
      after 3 weeks at 37 degrees C. Fibers (mAb-coated), stored at 37 degrees C in
      phosphate-buffered solution (0.02% NaN3), gave stable responses for 14 days.

PMID- 9011024
TI  - Kinetic modeling and analysis of a vesicle system for immunosensor development.
AB  - A novel mechanism is presented for immunosensor development that uses an
      immunological competition reaction in a vesicle system. This system consists of a
      suspension of reconstituted vesicles, channel agonist, protein linker to block
      the channels, voltage sensitive dye and analyte to be detected. In the proposed
      mechanism analyte serves a catalytic role as individual analytes competitively
      displace multiple channel linkers through association with one channel,
      dissociation and new associations with other channels. When one channel opens on
      a vesicle a permanent Nernst potential develops for that vesicle leading to
      fluorescence of voltage sensitive dyes. The time constant of the redistribution
      from linker-channel form to analyte-channel form is 0.92/k4 (k4 is the off-rate
      constant for the analyte-channel association) in the region of analyte
      concentrations less than 10(-9) M. Kinetic analyses show that several factors,
      including concentration of analyte or linker, number of channels per vesicle, on
      rate or off-rate constant of the linker-channel and on-rate constant of analyte
      channel complexes have significant effects on the minimum signal response time.

PMID- 9011025
TI  - Stability of bilayer lipid membranes on different metallic supports.
AB  - In order to arrive at an optimized s-BLM protocol, the influence of various
      metallic supports (silver, iridium and stainless steel) of different diameters
      (from 0.14 to 0.33 mm) on the process of forming and stability of supported
      phospholipid bilayer membranes was studied. In addition, experiments were made
      using different membrane-forming solutions, ionic strength and pH. The
      transmembrane resistance and the current ratio between bare and lipid-coated wire
      at +670 mV were measured. Teflon-coated stainless steel support (0.33 mm in
      diameter) covered with 2% crude ox brain fraction of phospholipids was most
      convenient for the formation of supported bilayer lipid membranes on solid
      support. The well-known stabilizing effect of cholesterol was confirmed for the s
      BLM system. Both the pH in the range 5.0-8.0 (silver and stainless steel
      supports) and the ionic strength (for all types of supports) in the range from
      0.025 to 0.1 mol/l at pH 7.0 were found not to be crucial.

PMID- 9011026
TI  - Effects of tris(4-chlorophenyl)methanol on the rat following short-term oral
      exposure.
AB  - The systemic toxicity of tris(4-chlorophenyl)methanol (TCPM) was studied in male
      and female rats following 4 weeks dietary exposure dosed at 1, 10 and 100 ppm. An
      increased spleen to body weight ratio was observed in males at 10 and 100 ppm and
      in females at 100 ppm. An increased liver to body weight ratio was detected in
      both sexes at 100 ppm. Dose-related increases in hepatic Phase-I (AH, APDM, EROD
      and PROD) and Phase-II (UDPGT, GST) enzyme activities were observed generally at
      10 and 100 ppm, with the elevation in PROD activity being the most marked.
      Increased urinary ascorbic acid was detected in both males and females after 1
      week of treatment at 100 ppm and after 4 weeks of treatment at 10 and 100 ppm. At
      10 and 100 ppm, elevated % lymphocytes were found in males, and higher white
      blood cell and lymphocyte counts were observed in females. In the liver, mild to
      moderate cytoplasmic changes consistent with proliferation of smooth endoplasmic
      reticulum were present in rats of both sexes at 10 and 100 ppm, and increased
      number of hepatocytes undergoing apoptosis were observed in male rats at 100 ppm.
      Mild splenic changes consisting of sinus hyperplasia in males and females at 100
      ppm and mantle zone atrophy in males at 100 ppm were also observed. It was
      concluded that TCPM at a dietary concentration of 10 ppm (equivalent to 1.2
      mg/kg/day) produced systemic changes in rats that included various hepatic
      effects, increased splenic weight, and modulations in white blood cells and
      lymphocyte counts.

PMID- 9011027
TI  - Synthesis and analysis of mixed chlorinated-fluorinated dibenzo-p-dioxins and
      dibenzofurans and assessment of formation and occurrence of the fluorinated and
      chlorinated-fluorinated dibenzo-p-dioxins and dibenzofurans.
AB  - Various mixtures of chlorinated-fluorinated dibenzodioxins (PCFDD), dibenzofurans
      (PCFDF) and biphenyls (PCFB) were synthesized. For trace analysis, we compared
      the behavior of PCFDD/PCFDF and chlorinated congeners in extraction, enrichment
      and clean-up steps. To establish GC/MS analysis, various columns were tested,
      temperature programs were optimized and for MS-identification specific masses
      were selected from the mass spectra. To evaluate the possibility of formation of
      these compounds in thermal processes, samples from the aluminum-producing
      industry and products of pyrolysis of chlorofluoro- hydrocarbons (FCKW) on a
      laboratory scale were analyzed. At present, the most important potential sources
      of fluorinated or mixed chlorinated-fluorinated dioxins, furans and biphenyls -
      combustion processes and large scale chemical production - do not cause
      significant environmental contamination at least in the areas considered.
      However, in a sample of filter dust from the refining process of aluminum using
      freon 12 we found high amounts (4.5 g/kg !) of chlorinated and chlorinated
      fluorinated aromatic compounds including chlorinated-fluorinated dibenzofurans
      and biphenyls. Since the FCKW ban in Europe, this procedure was modified in 1992,
      replacing freon 12 by a mixture of chlorine and argon. The PFDD/PFDF
      concentration in the fluorophenols was between 0.45 and 120 micrograms/kg. The
      fluorobenzenes analyzed contained between 15 and 70 mg/kg fluorinated biphenyls.

PMID- 9011028
TI  - Metabolic degradation, inducing potency, and metabolites of fluorinated and
      chlorinated-fluorinated dibenzodioxins and dibenzofurans.
AB  - The metabolic degradation of fluorinated, chlorinated-fluorinated and chlorinated
      congeners was measured in liver homogenate of NMRI mice. While in the time period
      between 0 and 240 min no degradation of the 2,3,7,8-TCDD/TCDF could be detected,
      for all fluorinated congeners a perceptible degradation was found, even for the
      2,3,7,8-TFDD. Stepwise chlorination of the 2,3,7,8-fluorinated congeners leads to
      a decrease of the degradation rate. In the EROD test, the exchange of chloro-
      with fluorosubstituents in the 2,3,7,8-TCDF leads to a decrease of induction
      potency. 3,7-Dichloro-2,8-difluorodibenzofuran was about 1/1000th as potent as
      2,3,7,8-TCDF, while 2,3,7,8-TFDF was complete inactive. Comparison of the
      metabolic rates of different TCDD with those of the analogous TFDD demonstrates
      that the order of enzymatic degradation of different TCDD and the analogous TFDD
      is identical. The TFDD are degraded slightly faster than the corresponding TCDD.
      Surprisingly 1,4,6,9-TXDD showed the second slowest metabolic rate of the
      fluorinated and chlorinated TXDD after 2,3,7,8-TXDD although none of the 2,3,7,8
      positions were substituted. Judging from 2,3,7,8-TFDD and 1,7-dichloro-2,8
      difluorodibenzofuran the metabolic pathway of fluorinated and chlorinated
      fluorinated congeners seem to be comparable to the chlorinated congeners.

PMID- 9011029
TI  - Cholinergic factors are not involved in the delayed diet passage from the crop of
      chicks given medium chain triacylglycerol.
AB  - The role of cholinergic mechanisms in the delayed food passage from the crop
      induced by medium chain triacylglycerol was investigated in the young chicken.
      Vagotomy altered the crop emptying of chicks given dietary long chain
      triacylglycerol, but did not alter it in chicks given dietary medium chain
      triacylglycerol. On the contrary, denervation in the cranial rete and lateral
      commissure of the gizzard further inhibited the food passage induced by medium
      chain triacylglycerol. Administration of cisapride, which induces acetylcholine
      release from the myenteric nerves, and atropine, a muscarinic cholinergic
      antagonist, both delayed crop emptying of chicks given medium chain
      triacylglycerol. These results demonstrate that cholinergic factors are not
      involved in the delayed forward movement of the food containing medium chain
      triacylglycerol from the crop of chicks.

PMID- 9011030
TI  - Role of dietary fatty acids on energetics and torpor in the Chilean mouse-opossum
      Thylamys elegans.
AB  - We hypothetized that the Chilean mouse-opossum Thylamys elegans needs
      micronutrients that are in fruits and seeds, and the unsaturated fatty acids are
      such micronutrients that may allow individuals of this species to experience
      longer torpor bouts, lower body temperatures during torpor and higher energy
      savings during wintertime. To test this hypothesis, we studied: 1) wintertime
      preferences by artificial diets rich in saturated fatty acids, unsaturated fatty
      acids and control diets, and 2) the effect of acclimation to dietary fatty acids
      on the energetics and torpor patterns in this species. When individuals where
      allowed to choose between the experimental diets they always selected the
      unsaturated fatty acid diet. After 4 weeks of dietary acclimation, the average
      daily metabolic rate was not significantly different among treatments, neither
      was minimum metabolic rate during torpor significantly different, in spite of a
      tendency to lower values that was detected under unsaturated fatty acid
      treatment. A similar pattern was observed when body temperature during torpor was
      compared among treatments. Two explanations are proposed: 1) Acclimation time was
      not sufficient to obtain statistical significance, but physiological differences
      and 2) metabolic rate during torpor are not affected by dietary lipids in this
      species.

PMID- 9011031
TI  - Co-distribution of tropomyosin and alpha-actinin with actin in Psammobatis
      extenta electrocytes brings out their similarity with muscle fiber cytoplasm.
AB  - Electric organs of Psammobatis extenta (Rajiformes) electric fish derive from
      myoblasts of the caudal region (16). Here we study the presence of muscle
      proteins, actin and the actin-binding proteins, alpha-actinin and tropomyosin, in
      the electrocytes by means of biochemical approaches, scanning electron microscopy
      and immunocytochemical methods. NBD-phallacidin is employed to detect the
      filamentous form of actin (F-actin). Immunoblots of actin and alpha-actinin from
      P. extenta skeletal and smooth muscle show that the electric organ forms of actin
      and alpha-actinin correspond to muscle types. Scanning electron microscopy shows
      that P. extenta electrocytes are highly polarized cells, semicircular in shape,
      with an anterior, concave innervated face and a posterior, convex, non-innervated
      face. The immunofluorescence patterns of alpha-actinin and tropomyosin
      distribution are similar to those of actin, in that these epitopes appear to
      occur throughout the entire electrocyte cytoplasm. F-actin, as revealed by NBD
      phallacidin fluorescence, was also found throughout the cytoplasm. This is the
      first time that evidence is presented to demonstrate the existence of muscle
      actin in this weak electric fish species electrocyte. The close evolutionary
      connection to that of muscle cells is discussed.

PMID- 9011032
TI  - Impact of ethanol stress on components of the allantoic fluid of the chicken
      embryo.
AB  - Recent studies showed that the allantoic fluid of the chicken embryo is a depot
      for stress-released catecholamines and many free amino acids and related
      compounds, and that it is separated from plasma and the amniotic fluid by
      selective barriers. To gain further insights into the functions of the allantois
      and its barriers, we studied the impact of stress (intra-allantoic injection of
      0.1 ml ethanol) on 39 free amino acids and related compounds of the allantoic
      fluid. Using an HPLC-fluorometric method, we found that the concentration of
      seven substances was significantly increased 20 min after injection of ethanol,
      and back to control levels within 40 minutes. Five of these compounds
      (asparagine, alanine, leucine, tyrosine, lysine) had previously been shown to
      occur in plasma at concentrations above those in the allantoic fluid. However,
      taurine and phosphoethanolamine increased in the allantoic fluid even though
      their concentrations in plasma tended to be lower than in allantoic fluid. These
      findings (1) reveal the existence of complex embryonic/extraembryonic
      autoregulations, and (2) raise the question of the regulatory mechanisms involved
      in the transfer of substances across the allantoic barrier(s).

PMID- 9011033
TI  - Regulation of substances in allantoic and amniotic fluid of the chicken embryo.
AB  - Traditionally, the avian allantois has been considered a respiratory organ and a
      dumping ground for metabolic wastes. We tested the hypothesis that the allantoic
      fluid is also a depot for free amino acids and related compounds. To gain further
      insight in the specific role of the allantoic fluid, we included plasma and the
      amniotic fluid in this study. The work was carried out in 13- and 14-day-old
      chicken embryos. Using an HPLC-fluorometric technique, 40 of the 41 amino acids
      and related compounds investigated were detected. The amniotic fluid contained 32
      compounds, while plasma and allantoic fluid contained 38 and 39 compounds,
      respectively. The glucose concentration was determined with a hexokinase
      technique. It was highest in plasma and lowest in the amniotic fluid. We
      identified three barriers that hyper- and hyporegulate a number of compounds: (1)
      a blood/allantois barrier, (2) a blood/amnion barrier, and (3) an
      allantois/amnion barrier. Compared with plasma and allantoic fluid, the amniotic
      fluid is a mostly hyporegulated environment.

PMID- 9011034
TI  - Seasonal variations in the frontal organ of the frog: structural evidence and
      physiological correlates.
AB  - Histological study of the frontal organ in the frog, Rana esculenta, was
      performed during spring, summer, autumn and winter. In semithin sections stained
      with toluidine blue, cells containing a vacuole were clearly detected during
      spring, and considerably increased during summer. Such cellular elements were
      absent in the frontal organ during autumn and winter. This morphological evidence
      of seasonal variation was supported by extracellular recording in the frontal
      organ in different seasons. Spontaneous firing rate was found to increase from
      the spring to the summer, and to decrease from the autumn to the winter.
      Altogether, these data indicate that the frontal organ may represent an autonomic
      component of the pineal complex with a secretory function producing neurohormonal
      messages involved in the annual mechanism of the reproduction.

PMID- 9011035
TI  - Bibliography of comparative biochemistry and physiology A generated from the
      Current Awareness in Biological Sciences database.

PMID- 9011036
TI  - Protein secretion in streptomycetes.
AB  - Some aspects of the current knowledge on protein secretion in streptomycetes are
      presented including recent data on the identification of genes in the general
      secretory pathway, on the importance of the signal peptide structure and on the
      number of ribosome-binding sites inside signal peptides which can influence the
      production level of a gene product.

PMID- 9011037
TI  - Detection of the induction of Salmonella enterotoxin gene expression by contact
      with epithelial cells with RT-PCR.
AB  - All strains of Salmonella enterica investigated were found to carry the
      Salmonella enterotoxin gene (stn) as determined by PCR and hybridization studies.
      However, when using CHO-K1 cells for testing the toxicity of the strains, not all
      strains showed a toxic effect (cell elongation) on the cells or did so only at a
      low level. The cultivation of Salmonella in contact with epithelial cells (IEC-6)
      led to an increase in the production of toxin. The stn gene expression was
      detectable with the help of the RT-PCR after 3 h of incubation. The RNA of the
      strains was isolated, transcribed into cDNA (with MMLV-reverse transcriptase) and
      amplified using PCR. The PCR products were separated electrophoretically using a
      polyacrylamide gel and detected by silver staining.

PMID- 9011039
TI  - Exponential growth rates of species of the yeast genus Kluyveromyces.
AB  - Doubling times were measured during exponential growth of 19 strains belonging to
      10 of the 17 species of the yeast genus Kluyveromyces. Growth was in shaken
      aerobic batch culture at 25 degrees C, in a chemically defined medium with D
      glucose as sole carbon source. Doubling times were strikingly uniform, being
      mainly between 2 and 3.5 h.

PMID- 9011038
TI  - Isolation and characterization of the integration host factor genes of
      Pasteurella haemolytica.
AB  - Using a bacteriophage lambda complementation system in Escherichia coli, we
      cloned genes encoding subunits of the heterodimeric DNA binding/bending protein,
      integration host factor, from the bovine pathogen, Pasteurella haemolytica.
      Complementation of ihfA and ihfB mutations in E. coli demonstrated that the P.
      haemolytica gene products form functional heterologous heterodimers. The ihfA and
      ihfB genes encode polypeptides predicted to be 99 and 93 amino acids long,
      respectively, and are very similar to integration host factor subunits from other
      Gram-negative bacteria, although phylogenetic analysis indicated that the P.
      haemolytica sequences are distantly related to those from other bacteria. Most
      significant amino acid differences were restricted to the amino-terminal domains
      of the predicted peptides.

PMID- 9011040
TI  - Identification of the gene (aphA) encoding the class B acid
      phosphatase/phosphotransferase of Escherichia coli MG1655 and characterization of
      its product.
AB  - An open reading frame located in the tyrB-uvrA intergenic region of the
      Escherichia coli MG1655 chromosome was identified as encoding the class B acid
      phosphatase of this species on the basis of cloning and expression experiments. A
      protocol for purification of the enzyme (named AphA) was developed, and its
      properties were analyzed. The enzyme is a 100-kDa homotetrameric protein which
      apparently requires a metal co-factor for activity. Similarly to other bacterial
      class B acid phosphatases, it is able to dephosphorylate several organic
      phosphomonoesters as well as to catalyze the transfer of low-energy phosphate
      groups from phosphomonoesters to hydroxyl groups of various organic compounds.

PMID- 9011041
TI  - 13C-NMR study of glucose and pyruvate catabolism in four acetogenic species
      isolated from the human colon.
AB  - Glucose fermentation by four acetogenic species (two Clostridium strains, one
      Streptococcus strain and Ruminococcus hydrogenotrophicus) isolated from the human
      colon was of a mixed-acid type, whereas pyruvate metabolism was characterised by
      homoacetogenesis. Acetate formation from [1-13C] and [2-13C]glucose was
      consistent with the formation of acetyl-SCoA from pyruvate generated by the
      Embden-Meyerhof-Parnas pathway. Labelling of lactate and ethanol demonstrated
      that these metabolites were formed by reduction of pyruvate and acetyl-SCoA,
      respectively. In contrast, the reductive pathway of acetate formation was the
      preferential means of re-oxidising cofactors formed during [1-13C]pyruvate
      catabolism.

PMID- 9011042
TI  - Capsaicin as an inhibitor of the growth of the gastric pathogen Helicobacter
      pylori.
AB  - Capsaicin, the active ingredient in chili, has been implicated as both a
      cytoprotective and a detrimental agent to the gastric mucosa. The effect of
      capsaicin on Helicobacter pylori has not been investigated previously. Therefore,
      we performed in vitro time- and concentration-dependent studies to examine the
      growth of H. pylori in the presence of capsaicin. Capsaicin specifically
      inhibited growth of H. pylori dose-dependently at concentrations greater than 10
      micrograms ml-1 (P < 0.05) but did not inhibit the growth of a human fecal
      commensal Escherichia coli strain. Bactericidal activity was observed within 4 h.
      Capsaicin continued to exhibit bactericidal activity when incubated at pH values
      as low as 5.4. Ingestion of chili, therefore, could have a protective effect
      against H. pylori-associated gastroduodenal disease. This effect deserves further
      study in animal models.

PMID- 9011043
TI  - Immune response to vaccination with DNA encoding the bovine viral diarrhea virus
      major glycoprotein gp53 (E2).
AB  - Bovine viral diarrhea virus (BVDV) is a worldwide pathogen in cattle which has
      not been controlled by classical vaccination. The region encoding the BVDV major
      glycoprotein gp53 (E2) known to possess virus-neutralizing activity was cloned
      into a mammalian expression vector under the human cytomegalovirus (CMV)
      intermediate early promoter. Intramuscular and intradermal administration of the
      recombinant plasmid DNA into BALB/c mice induced BVDV gp53-specific antibody
      responses to both biotypes (cytopathic and noncytopathic) of BVDV genotype 1, and
      to cytopathic BVDV genotype 2. BVDV-neutralizing antibodies were generated
      against BVDV genotype 1 strains and they also persisted 6 months after the last
      injection.

PMID- 9011044
TI  - Conservation of genetic linkage with map expansion in distantly related crosses
      of Agaricus bisporus.
AB  - A previous map of the genome of a hybrid strain which had European parents
      belonging to the secondarily homothallic fungus Agaricus bisporus var. bisporus
      appeared to be unusually compact, with a particularly recombophobic segment in
      the central part of chromosome I. A new map of this segment was constructed based
      on allelic segregations among 103 homokaryotic offspring of an A. bisporus hybrid
      between a European parent of the var. bisporus and a Californian parent of the
      heterothallic var. burnettii. Markers completely linked on the previous map were
      distributed along 28 cM in the new map. These results suggest that the greater
      recombination rate could be correlated with the outbreeding behaviour of the var.
      burnettii.

PMID- 9011045
TI  - A unique DNA sequence of human enterotoxigenic Escherichia coli enterotoxin
      encoded by chromosomal DNA.
AB  - We detected Ent plasmids in 300 strains of human enterotoxigenic Escherichia
      coli, but one strain, E. coli 240-3, had neither a small nor a large plasmid and
      encoded the heat-labile enterotoxin (LTh(240-3)) gene on its chromosome. DNA
      sequences showed that LTh(240-3) differed by 12 and 14 base pairs from LT (LTh)
      and LT (LTp) from human H10407 and porcine EWD299 strains, respectively. In
      deduced precursor toxins, LTh(240-3), LTh and LTp differed from LTh, LTp and
      LTh(240-3) at nine, eight and eleven positions, respectively. These data suggest
      that although LTh(240-3) encoded in the chromosome is antigenically similar to
      LTh, it cannot be grouped with LTh due to differences in its DNA and amino acids
      sequences.

PMID- 9011046
TI  - Analysis of the icsBA locus required for biosynthesis of the inner core region
      from Neisseria meningitidis lipopolysaccharide.
AB  - By deletion mutagenesis in the entire meningococcal chromosome, we have
      previously identified the icsA gene, which encodes the glycosyltransferase
      required for adding GlcNAc to Hep-II in the inner core of meningococcal LPS. This
      gene has homology to several LPS glycosyltransferases, notably to rfaK from
      Salmonella typhimurium and bplH from Bordetella pertussis, both of which encode
      GlcNAc transferases. Directly upstream of icsA is an ORF showing significant
      homology to the hypothetical protein HI0653 from the Haemophilus influenzae
      genome sequence, and to a lesser degree to putative glycosyltransferases from
      Streptococcus thermophilus and Yersinia enterocolitica. Insertional inactivation
      of this ORF resulted in a meningococcal strain with truncated LPS. We have named
      this new LPS-involved gene icsB. Differences in binding of monoclonal antibodies
      and in mobility on Tricine-SDS-PAGE showed that LPS from icsA and icsB mutants is
      similar but not identical. On the basis of these results, we postulated that the
      new gene encodes the glycosyltransferase required for adding Glc to Hep-I.
      Structural analysis of purified mutant LPS by electrospray mass spectrometry was
      used to verify this hypothesis. The composition determined for icsA and icsB is
      lipidA-(KDO)2-(Hep)2.PEA and lipidA-(KDO)2-(Hep)2.PEA-GlcNAc, respectively. The
      icsA and icsB genes thus form an operon encoding the glycosyltransferases
      required for chain elongation from the lipidA-(KDO)2-(Hep)2 basal structure, with
      IcsA first adding GlcNAc to Hep-II and IcsB subsequently adding Glc to Hep-I.
      Only then is completion of the lacto-N-neotetraose structure possible through the
      action of the IgtA-E genes.

PMID- 9011047
TI  - Partial purification of (1,3)-beta-glucan synthase from Candida albicans.
AB  - (1,3)-beta-Glucan synthase from Candida albicans was solubilized from microsomal
      membranes using the detergent 3-[(3-cholamidopropyl) dimethylammonio]-1-propane
      sulfonate (Chaps). Effective solubilization was dependent upon the strain and the
      method used to detect enzyme activity. The solubilized enzyme was purified over
      765-fold using a modified product entrapment technique. Bovine serum albumin, an
      activator of glucan synthase, precipitated proteins during product entrapment and
      was replaced with BSA immobilized on agarose beads. SDS-PAGE analysis revealed a
      prominent 187-kDa band present in the product entrapped pellet as well as several
      additional polypeptides at 227, and 187, 182 and 39 kDa which were not prevalent
      in crude preparations.

PMID- 9011048
TI  - Non-motile mini-transposon mutants of Bordetella bronchiseptica exhibit altered
      abilities to invade and survive in eukaryotic cells.
AB  - Non-motile mutants of Bordetella bronchiseptica were generated after mini
      transposon mutagenesis. One non-motile mutant (designated VMM1) was derived from
      the bvg-positive strain BB7865 and four mutants (designated AMM1-4) were derived
      from the isogenic bvg-negative strain BB7866. Southern hybridisation analysis
      indicated that loss of motility was not due to the disruption of the flagellin
      subunit gene. Western blot and transmission electron microscopic analysis
      indicated that three of the five mutants expressed neither the flagellin subunit
      (40 kDa) nor flagella whereas one mutant expressed intact flagella under all
      conditions tested. One unique bvg-negative mutant, AMM4, exhibited temperature
      dependent repression of flagella biosynthesis and motility at 37 degrees C. The
      ability of AMM4 to invade and survive in HeLa cells was significantly decreased.

PMID- 9011049
TI  - Rapid identification and typing of Staphylococcus aureus by nested PCR amplified
      ribosomal DNA spacer region.
AB  - We designed a polymerase chain reaction (PCR) assay for rapid detection of
      prokaryotic 16S-23S spacer regions. This PCR assay consisted of nested DNA
      amplifications. The first-step PCR was able to detect the general presence of
      eubacteriales with a unified set of universal primers. The universal primers were
      selected from highly conserved regions in 16S and 23S ribosomal RNA (rRNA) genes
      and amplified DNAs from all 62 different species of bacteria tested. In the
      second-step PCR, the identification primers could detect four important bacterial
      species through amplification of the rRNA spacer regions between the 16S-23S rRNA
      genes. For Staphylococcus aureus, intraspecies variation in spacer amplification
      products was observed with S. aureus specific primers. We suggest that the nested
      PCR assay could be used as a novel method for the identification and typing in
      epidemiological studies of S. aureus.

PMID- 9011050
TI  - Cloning and characterization of the gene for the metalloprotease enterotoxin of
      Bacteroides fragilis.
AB  - The Bacteroides fragilis enterotoxin is an extracellular zinc metalloprotease
      that has been implicated in diarrheal disease of humans and animals. This toxin
      causes fluid accumulation in intestinal loops and is cytotoxic for HT-29 cells,
      an intestinal carcinoma cell line. Here we report the cloning and sequencing of
      the toxin gene (bftP). bftP is 1191 nucleotides coding for a 397 amino acid
      protein of 44.4 kDa. The toxin has a signal peptide of 18 amino acids that is
      typical of many lipoproteins followed by a 379 amino acid protoxin. The portion
      of the protoxin found in culture filtrates and stools begins at amino acid 212.
      An additional open reading frame located immediately upstream shows some sequence
      identity with cobra cytotoxins. If expressed, the ORF protein product could also
      play a role in the virulence of B. fragilis.

PMID- 9011051
TI  - Complementation of Listeria seeligeri with the plcA-prfA genes from L.
      monocytogenes activates transcription of seeligerolysin and leads to bacterial
      escape from the phagosome of infected mammalian cells.
AB  - Infection experiments have shown that the avirulent species Listeria seeligeri
      invaded the enterocyte-like cell line Caco-2 with low efficiency but was unable
      to escape from the phagosome. Introduction of the listeriolysin gene (hly) from
      L. monocytogenes into L. seeligeri via a recombinant plasmid did not change these
      characteristics. No measurable transcription of this gene or of the structurally
      intact chromosomal seeligerolysin gene (lso) was detected. Transformation with a
      plasmid carrying the bicistronically transcribed plcA-prfA genes from L.
      monocytogenes resulted in the efficient expression of the plasmid-encoded
      transcription activator PrfA, a readily detectable synthesis of seeligerolysin
      and the escape of the bacteria from the phagosome of infected mammalian cells,
      followed by intracytoplasmic multiplication.

PMID- 9011052
TI  - Dissection of the promoter/operator region and evaluation of N-acylhomoserine
      lactone mediated transcriptional regulation of elastase expression in Pseudomonas
      aeruginosa.
AB  - In Pseudomonas aeruginosa, expression of the lasB gene which codes for the
      metalloprotease, elastase, depends on small diffusible N-acylhomoserine lactones.
      lasB expression is regulated through the interactions of N-3-oxododecanoyl-L
      homoserine lactone and N-butanoyl-L-homoserine lactone with the transcriptional
      activators LasR and VsmR(RhlR), respectively. To investigate lasB expression
      further, we first located the transcriptional start site to a position 141 bp
      upstream from the translational start site. Using this information, we
      constructed a series of plasmids containing consecutive 5' deletions of the
      upstream region of lasB fused to a promoterless chloramphenicol acetyltransferase
      reporter gene. The results obtained indicate that three regions are required for
      efficient transcription of lasB; a 35 bp palindromic sequence located at +26 to
      +60 bp upstream from the translation start site, and two regions located upstream
      of the transcription start site, at -135 to -85 bp and -63 to -26 bp,
      respectively. Deletion of the latter region results in the loss of both N
      butanoyl-L-homoserine lactone- and N-3-oxododecanoyl-L-homoserine lactone
      mediated stimulation of lasB expression and provides further support for the role
      of this operator site as a target for either or both LasR and VsmR.

PMID- 9011053
TI  - Advances in determination of antibiotic residues.

PMID- 9011054
TI  - Determination of antifungals in rodent diet by supercritical fluid extraction
      followed by packed column supercritical fluid chromatography with ultraviolet
      detection.
AB  - Supercritical fluid extraction (SFE) followed by packed column supercritical
      fluid chromatography with ultraviolet detection was evaluated as a quantitative
      method for determining 4 antifungals (fluconazole, tioconazole, hexaconazole, and
      UK-47,265) in rodent diet. Chromatography was achieved with a cyano-bonded silica
      column, UV detection at 210 nm, and methanol-modified supercritical carbon
      dioxide as mobile phase. The effects of modifier concentration, temperature, and
      column pressure on antifungal retention time was studied. Off-line SFE was
      optimized at 2 spike levels, ranging from 0.5 to 10 g/kg, for each of the 4
      antifungals. Average recoveries ranged from 79.0% for UK-47,265 to 96.5% for
      hexaconazole. Overall, the procedure provides a suitable method for analyzing
      antifungals in spiked rodent diet.

PMID- 9011055
TI  - Rapid determination of ampicillin in bovine milk by liquid chromatography with
      fluorescence detection.
AB  - A rapid and sensitive liquid chromatographic (LC) method was developed for the
      determination of ampicillin residues in raw bovine milk, processed skim milk, and
      pasteurized, homogenized whole milk with vitamin D. Milk samples were
      deproteinized with trichloroacetic acid (TCA) and acetonitrile. After
      centrifugation, the clear supernatant was reacted with formaldehyde and TCA under
      heat. The major fluorescent derivative of ampicillin was then determined by
      reversed-phase LC with fluorescence detection. Average recoveries of ampicillin
      fortified at 5, 10, and 20 ppb (ng/mL) were all > 85% with coefficients of
      variation < 10%. Limits of detection ranged from 0.31 to 0.51 ppb and limits of
      quantitation, from 0.66 to 1.2 ppb. After appropriate validation, this method
      should be suitable for rapid analysis of milk for ampicillin residues at the
      tolerance level of 10 ppb.

PMID- 9011056
TI  - Determination of methylene blue in channel catfish (Ictalurus punctatus) tissue
      by liquid chromatography with visible detection.
AB  - Methylene blue (MB) is a thiazine dye that, although not regulated for use with
      edible fish, may sometimes be used as a chemotherapeutic agent in the aquaculture
      industry. A liquid chromatographic (LC) method was developed for the
      determination of MB in fish muscle. MB was extracted from catfish tissue with an
      acetonitrile-acetate buffer solution containing hydroxylamine and toluenesulfonic
      acid, partitioned into methylene chloride, and cleaned up on alumina and
      carboxylic acid solid-phase extraction cartridges. MB concentrations were
      determined by LC with visible detection at 660-665 nm. Recoveries of MB from
      catfish fortified at 10-50 ng/g were 75-90% (RSDs, 5-12%). Leucomethylene blue
      also can be recovered from catfish tissue as the MB colored form at low levels
      with similar recoveries. Analysis of catfish exposed to MB in a bath treatment at
      5 ppm MB for 1 h recovered 10-20 ppb of the drug in the muscle tissue. The low
      tissue concentration suggests poor absorption of this drug compared with other
      antifungal dyes that tend to concentrate and remain in fish tissue at high
      levels.

PMID- 9011057
TI  - Assurance Escherichia coli O157:H7: a comparative validation study.
AB  - A wide variety of food products, with emphasis on raw meat products, were
      analyzed simultaneously by 3 methods: the Assurance Escherichia coli O157:H7
      (EHEC) enzyme immunosorbent assay (EIA), the EHEC visual immunoprecipitate assay
      (VIP), and a modified Bacteriological Analytical Manual (BAM) culture method.
      This paper reports results of a comparative study of the Assurance and modified
      BAM methods. In this comparative study, 1050 samples and controls gave false
      negative rates of 1.0 and 0%, respectively, for the Assurance EIA and the
      modified BAM culture methods. The overall agreement between the 2 methods was
      99.4%. Cultural confirmation of presumptive positive samples was problematic
      because competitive flora were present in higher levels than EHEC in the
      enrichment broth after incubation and the target organism had nondescript
      characteristics on the primary selective agar, hemorrhagic coli agar, which
      necessitated picking of additional colonies in many instances.

PMID- 9011058
TI  - Escherichia coli O157:H7 visual immunoprecipitate assay: a comparative validation
      study.
AB  - A wide variety of food products, with emphasis on raw meat products, were
      analyzed simultaneously by 3 methods: the Escherichia coli O157:H7 (EHEC) visual
      immunoprecipitate assay (VIP), the Assurance EHEC enzyme immunoassay, and a
      modified Bacteriological Analytical Manual (BAM) culture method. This paper
      reports results of a comparative study of the VIP and modified BAM methods. In
      this comparative study, 1050 samples and controls gave false-negative rates of
      1.0 and 0%, respectively, for the VIP and the modified BAM culture methods. The
      overall agreement between the 2 methods was 99.4%. Cultural confirmation of
      presumptive positive samples was problematic because competitive flora were
      present in higher levels than EHEC in the enrichment broth after incubation and
      the target organism had nondescript characteristics on the primary selective
      agar, hemorrhagic coli agar, which necessitated picking of additional colonies in
      many instances.

PMID- 9011059
TI  - Determination of platinum in wine by graphite furnace atomic absorption
      spectrometry.
AB  - A method based on graphite furnace atomic absorption spectrometry (GFAAS) was
      developed for determining platinum in wine. Wine samples were prepared by
      microwave acid digestion or dry mineralization. The method of standard addition
      was used for Pt determination in untreated wine samples and mineralized samples.
      Analyte modifiers and furnace conditions were optimized. Effects of cations
      (Mg2+, Ca2+, K+, Na+, and NH4+) and anions (PO4(3)-, SO4(2)-) were tested
      separately and in combination. Analytical characteristics of the method were
      optimized for analyte recovery and signal enhancement. Recoveries ranged from
      92.5 to 102%, and precision reproducibility relative standard deviation varied
      from 7.5 to 10%. Red, rose, and white wines from France were analyzed. Platinum
      levels found in most wines were very low (< 10 micrograms/L).

PMID- 9011060
TI  - Modification of AOAC multiresidue method for determining synthetic pyrethroid
      residues in fruits, vegetables, and grains. Part III: Studies of analyte
      stability and method ruggedness.
AB  - The stability of 8 synthetic pyrethroids in 9 crops during storage for 90 days
      were studied. The 8 pyrethroid insecticides were highly persistent in the 6
      grains during storage. But their stabilities in 3 kinds of fruits and vegetables
      were different from those in the 6 grains: Most of them were degraded. Florisil
      purification conditions were studied with 6 batches of Florisil from 3 countries
      at various extents of deactivation and amounts. The best conditions of Florisil
      purification found in this present research agree with those found 1 year ago.
      The efficiencies of acetonitrile and acetone to extract the 8 pyrethroids from 6
      fruit and vegetable samples were compared. The extraction efficiency of acetone
      was competitive with that of acetonitrile for the 6 fruit and vegetable samples.
      Method performance was evaluated by 6 analysts from different areas. The
      ruggedness tests demonstrate further that the proposed method is simple, accurate
      with good precision, and suitable for multiresidue analysis of pyrethroids in
      various agriculture products.

PMID- 9011061
TI  - Fine tuning a bile-enzymatic-gravimetric total dietary fiber method.
AB  - A recently proposed bile-enzymatic-gravimetric total dietary fiber (TDF) method
      was modified and the new procedure was compared with the original method, the
      traditional AOAC enzymatic-gravimetric determination (AOAC Official Method
      985.29), and another simplified AOAC procedure by analyzing several diet
      composites, including National Institute of Standards and Technology 1548 total
      diet reference material. The original and modified bile-enzymatic-gravimetric
      procedures also were compared by analyzing 9 food samples from a collaborative
      study of the original method. The modified method consistently yielded values
      about 10% lower than the original method but closer to reference values and to
      values from AOAC Official Method 985.29, suggesting results that are more in line
      with accepted TDF standard methodology. Our modified method was used to analyze
      180 fresh-frozen diet composites with TDF values ranging from 0.6 to 3.2 g/100 g
      wet weight. Samples were from 2 multicenter feeding studies sponsored by the
      National Heart, Lung and Blood Institute: DELTA (Dietary Effects on Lipoproteins
      and Thrombogenic Activity) and DASH (Dietary Approaches to Stop Hypertension).
      The mean relative standard deviation (RSD) for duplicate analyses was 1.1%. For
      40 assays of a quality control diet composite over 9 months, the standard
      deviation was 0.1 g/100 g wet weight (4.9% RSD), indicating the method's
      excellent precision for routine use.

PMID- 9011062
TI  - Effect of seeds on bile-enzymatic-gravimetric analysis of total dietary fiber.
AB  - Dietary fiber sometimes is defined chemically as nonstarch polysaccharides plus
      lignin or as other specific chemical entities. Analysis of dietary fiber
      according to a chemical definition typically involves gas chromatography, which
      allows separation and quantitation of chemical constituents that are added to
      arrive at a dietary fiber value. Other definitions of fiber are broader, defining
      it to be whatever is not digested in the alimentary tract. Analytically, this
      definition translates into the gravimetric sum of the material remaining after a
      series of enzymatic and chemical treatments that simulate in vivo digestion.
      Various methods reflect the gravimetric definition, which might include as
      dietary fiber some protein, resistant starch, and even lipids that are not
      digested by particular assay conditions. We used a recently proposed bile
      enzymatic-gravimetric assay for total dietary fiber on commonly consumed seeds
      (hulled and unhulled sesame, caraway, and poppy) and visually found these seeds
      to be undigested. We then determined the impact of the undigested seeds on
      measured dietary fiber content by spiking homogenized daily menus with 5% by
      weight of these seeds and calculating recoveries with 2 assumptions: seeds are
      100% fiber because they are not digested, and the fiber content of seeds is as
      determined by assay. Calculated recoveries were very different depending on which
      assumption was made (71-90% or 99-109%, respectively), and the difference was
      closely related to the seed's protein content.

PMID- 9011063
TI  - Effect of lipid extraction methods on total dietary fiber and nonstarch
      polysaccharide contents of selected nuts and seeds.
AB  - Three extraction methods were used to remove lipid materials from 8 edible nuts
      and seeds before analysis for their total dietary fiber (TDF) and nonstarch
      polysaccharide (NSP) contents. Portions of ground materials were extracted by: n
      hexane, followed by 80% methanol, n-hexane-acetic acid (95 + 5, v/v), and
      supercritical carbon dioxide. Defatted samples were gelatinized in water and
      incubated with amyloglucosidase; 95% ethanol was added to the hydrolyzates, and
      the residues were collected on tared glass crucibles. TDF was calculated
      according to a simplified enzymatic-gravimetric method developed in our
      laboratory, and NSP was determined as described by Englyst and coworkers. Dietary
      fiber values obtained with any of the extraction methods range from 3.47 g/100 g
      for cashews to 28.56 g/100 g for sunflower seeds. Nonstarch polysaccharide values
      range from 2.43 g/100 g for pecans to 5.56 g/100 g for peanuts. With the
      exception of sunflower seeds, samples extracted with supercritical carbon dioxide
      had lower TDF contents but similar amounts of NSP compared with samples extracted
      by the other 2 methods.

PMID- 9011064
TI  - Determination of decabromobiphenyl ether in water and sediment samples by gas
      chromatography with electron capture detection.
AB  - Traces of decabromobiphenyl ether (DBBE) in water and sediment were determined by
      capillary gas chromatography with electron capture detection. Rapid sample
      preparation techniques such as disk-type C18 solid-phase extraction and cartridge
      type Florisil extraction were used to clean up water and sediment samples,
      respectively. The detection limits of DBBE were 0.12 ng/mL and 9.7 ng/g in water
      and sediment, respectively. Average recoveries of DBBE added to river water, sea
      water, and sediment were 103%, with a relative standard deviation (RSD) of 8.6%;
      87%, with an RSD of 10.7%; and 91%, with an RSD of 6.3%, respectively.

PMID- 9011065
TI  - Coding of blend ratios of binary mixtures by olfactory neurons in the Florida
      spiny lobster, Panulirus argus.
AB  - The aim of this study was to investigate quality coding of blend ratios of binary
      mixtures by olfactory receptor cells in the spiny lobster. Three odorants
      (adenosine-5'-monophosphate, L-glutamate, and taurine) at 0.1-100 mumol.1(-1) and
      seven blend ratios of each of their binary mixtures at a total concentration of
      100 mumol.1(-1) were used. The olfactory cells recorded (n = 48) evoked across
      neuron patterns for single odorants that were well separated from each other.
      Across-neuron patterns varied with stimulus concentration but less than with
      stimulus type. Blend ratios of the three mixtures evoked across-neuron patterns
      that were orderly placed within a continuum between those elicited by the
      components. Mixture interactions, defined as a lack of independent effects by a
      mixture's components, occurred in 25, 24 and 37% of responses to blend ratios of
      glutamate/taurine, adenosine-5'-monophosphate/taurine, and glutamate/adenosine-5'
      monophosphate, respectively. These mixture interactions did not have a large
      enough effect on the across-neuron patterns for the mixtures such they would be
      novel relative to those of the single components. These results suggest that
      despite mixture interactions the quality of individual compounds is not lost when
      mixed. This corroborates behavioral studies showing that spiny lobsters have the
      ability to elementally process odor mixtures.

PMID- 9011066
TI  - The effect of neuropeptides from Limulus on its circadian rhythm in retinal
      sensitivity.
AB  - Retinal responses of the Limulus lateral eyes to light are greater at night than
      during the day. A circadian clock in the brain of the horseshoe crab controls
      these rhythmic changes of light sensitivity. The increase in sensitivity (as
      measured by the amplitude of the electroretinogram) is mediated at least in part
      by octopamine that is released from efferent axons terminating in the visual
      cells. Earlier studies indicate that certain factors in Limulus hemolymph can act
      in conjunction with octopamine. More recently, five neuropeptides (LP1-LP4 and
      Lip-HP) had been isolated from acetone extracts of the Limulus central nervous
      system using HPLC fractionation and radioimmunoassay with antisera against
      FMRFamide-like peptides for detection. Presently, we have injected into the
      Limulus lateral eye these five peptides and observed changes in retinal
      sensitivity. Injection during daytime had no immediate effect on that daytime
      electroretinogram but decreased the electroretinogram amplitude for the entire
      subsequent night (12 h). However, upon injection at night, we observed an
      immediate but only transitory decrease in electroretinogram amplitude for about 1
      h without effect on the subsequent daytime electroretinogram. We suggest that the
      peptides act antagonistically to octopamine and are highly dependent upon the
      activity state of the efferent nerve terminals.

PMID- 9011067
TI  - The maxillary palp of Drosophila: ultrastructure and physiology depends on the
      lozenge gene.
AB  - The ultrastructure and physiology of the maxillary palp of Drosophila
      melanogaster have been studied in wild-type and lozenge mutants. Olfactory
      physiology in the maxillary palp is shown to depend upon the lozenge(lz) gene.
      Reduced response amplitudes were recorded for all odorants tested, and the
      physiological defect was shown to map to the lz locus. The structure of the
      maxillary palp sensilla is described by scanning electron microscopy (SEM) at
      high magnification, initially in the wild-type. A linear arrangement of pores,
      connected by furrows, was found in one class of sensilla, the basiconic sensilla.
      In the lz3 mutant, morphological alterations in the basiconic sensilla and
      duplications of sensilla are documented by SEM. The correlation of structural
      abnormalities in the lz sensilla and physiological abnormalities in odorant
      response are consistent with an olfactory role for the basiconic sensilla of the
      maxillary palp.

PMID- 9011068
TI  - The Drosophila antenna: ultrastructural and physiological studies in wild-type
      and lozenge mutants.
AB  - The physiology and ultrastructure of the antenna in Drosophila melanogaster have
      been examined in wild-type and lozenge mutants. Scanning electron microscopy
      (SEM) of sensilla on the antennal surface has revealed that in the wild-type the
      basiconic sensilla contain linear arrays of pores connected by longitudinal
      furrows and transected by shorter furrows. Sensilla trichodea also are shown to
      have pores, as revealed by examining transverse sections by transmission electron
      microscopy (TEM); these data directly address a longstanding controversy.
      Coeloconic sensilla, previously described as "pit sensilla" and as "grooved"
      sensilla, are shown to rise directly from the antennal surface, as opposed to
      lying below the antennal surface in pits; the previously observed grooves
      correspond to the junctions between bundled, finger-like projections. This
      description of coeloconic sensilla is supported by analysis of lz mutants, in
      which the projections of coeloconic sensilla splay apart. Coeloconic sensilla are
      also shown to undergo duplication on the lz3 antenna. Physiological recordings
      from the antenna show that responses to all odorants tested are severely
      decreased in lz mutants. Measurements made from different parts of the antenna
      show similar defects. Evidence is provided that both the physiological and
      ultrastructural defects map to the lz locus.

PMID- 9011069
TI  - Depletion of CD4+ or CD8+ T-cells prevents Plasmodium berghei induced cerebral
      malaria in end-stage disease.
AB  - The role of T-cells in development of experimental cerebral malaria was analysed
      in C57B1/6J and C57B1/10 mice infected with Plasmodium berghei K173 or Plasmodium
      berghei ANKA by treatment with anti-CD4 or anti-CD8 mAbs. Mice were protected
      against cerebral malaria (CM) when anti-CD4 or anti-CD8 mAbs were injected before
      or during infection. Even in mice in end-stage disease, i.e. with a body
      temperature below 35.5 degrees C, treatment with anti-CD4 or anti-CD8 antibodies
      or the combination protected against CM, whereas chloroquine treatment was
      completely ineffective in inhibiting further development of the cerebral
      syndrome.

PMID- 9011070
TI  - Anti-oxidant enzymes in Cryptosporidium parvum oocysts.
AB  - Oocysts of Cryptosporidium parvum showed relatively low levels of SOD activity.
      The SOD which had a pI of 4.8 and an approximate molecular weight of 35 kDa
      appeared to be iron dependent. Catalase, glutathione transferase, glutathione
      reductase and glutathione peroxidase activity could not be detected, nor could
      trypanothione reductase. No NADH or NADPH oxidase activity could be detected, nor
      could peroxidase activity be demonstrated using o-dianisidine, guaiacol, NADPH or
      NADH as co-substrates. However, an NADPH-dependent H2O2 scavenging system was
      detected in the insoluble fraction.

PMID- 9011071
TI  - Two Encephalitozoon cuniculi strains of human origin are infectious to rabbits.
AB  - The microsporidian Encephalitozoon cuniculi can infect a wide variety of mammals
      including man. In this study, E. cuniculi isolates of animal origin were compared
      with 6 isolates obtained from HIV-infected patients. Based on results of Western
      blot analysis, random amplified polymorphic DNA (RAPD) and the sequence of the
      rDNA internal transcribed spacer (ITS) the isolates were classified into 3 groups
      with the repeated element 5'GTTT-3' in the ITS being a reliable genetic marker.
      Five isolates from Swiss patients were found to be homologous to isolates from
      Swiss rabbits (strain I). The sixth isolate from a patient from Mexico differed
      by all methods and could be attributed to E. cuniculi strain III that has been
      described from 2 dogs from the USA. All of these isolates were distinguished from
      isolates from blue foxes from Norway (strain II). Intraspecific nucleotide
      divergence of the SSU rRNA gene of E. cuniculi belonging to the 3 strains was in
      the same low range (0.00-0.15%) as was found for the corresponding sequence of 2
      E. hellem isolates. Groups of 2 rabbits were infected by oral inoculation of
      10(7) E. cuniculi spores (2 isolates from strain I of human and rabbit origin, 1
      from strain III) as shown by antibody responses and the re-isolation of the
      parasites from brain material. The results provide further evidence that per oral
      transmission of the parasite between various hosts is feasible.

PMID- 9011072
TI  - Molecular genetic analysis of human cystic hydatid cases from Poland:
      identification of a new genotypic group (G9) of Echinococcus granulosus.
AB  - We have used nuclear (ribosomal ITS1) and mitochondrial (ND1) sequences to
      characterize human and pig isolates of Echinococcus granulosus collected by fine
      needle aspiration biopsy (FNAB) in Poland. The data indicate clearly that the
      Polish patients were not infected with the common sheep strain (G1 genotype) of
      E. granulosus, normally associated with human cystic hydatid infection. Instead,
      the hydatid parasite infecting the Polish patients shares very similar ND1
      sequence with the previously characterized pig (G7) genotype but it also exhibits
      some clear differences. In particular, E. granulosus DNA from the Polish patients
      amplified a single ITS1 fragment in PCR and distinct ITS1-RFLP patterns were
      obtained after restriction digestion. The form of hydatid isolated from the
      Polish patients appears, therefore, to represent a distinct, previously
      undescribed genotype (designated G9) of E. granulosus.

PMID- 9011073
TI  - Schistosoma japonicum: immunolocalization of paramyosin during development.
AB  - This paper describes the localization of paramyosin immunoreactivity in
      Schistosoma japonicum and represents the first comparative immunolocalization
      study among schistosome adult, cercariae and lung schistosomula by electron
      microscopy. A polyclonal antibody was utilized to immunolabel paramyosin or
      paramyosin-like proteins. Paramyosin was localized within the muscle layer of all
      3 developmental stages. Furthermore, paramyosin was localized within granules of
      the post-acetabular glands of cercariae, and within the tegument matrix and
      surface of lung schistosomules. Adults and cercariae did not display any
      detectable paramyosin on the surface or within the tegument. The possible
      functions of paramyosin within S. japonicum and the relevance of these findings
      in relation to the reported protective properties of paramyosin as an anti
      schistosome vaccine target molecule are discussed.

PMID- 9011074
TI  - Necator americanus in inbred mice: evidence in support of genetically determined
      differences in the cellular immune response to a primary infection.
AB  - The blood and broncho-alveolar leucocyte (BAL) responses, to a primary Necator
      americanus infection, were studied in male BALB/c and NIH mice. Following
      percutaneous infection, a significant blood leucocytosis occurred in both the
      BALB/c and NIH strains. The peak response occurred, in both strains, on day 10
      p.i. and this was reflected in the eosinophil response which peaked at the same
      time-point. The change in blood eosinophil numbers, as a result of infection, was
      found to be the greatest recorded for any cell type. In BALB/c mice, however,
      infection elicited a significantly more intense total leucocyte, lymphocyte and
      eosinophil response than in NIH mice. In contrast, the BAL response was more
      intense in the NIH strain. Peak BAL responses were observed between days 12 and
      16 p.i., in both strains, and the change in broncho-alveolar eosinophil numbers,
      as a result of infection, was found to be the greatest recorded for any cell
      type. The relationship between the observed leucocyte responses and resistance to
      the migrating larvae of a primary infection is discussed.

PMID- 9011075
TI  - Suppression of mitogen-induced IL-2R alpha expression in PBL by serum from
      microfilaraemic rats chronically infected with Brugia pahangi.
AB  - To study immunological responses in filarial infections, interleukin-2 receptor
      alpha (IL-2R alpha) expression in the peripheral blood lymphocytes (PBL) of Lewis
      rats infected with Brugia pahangi was observed by flow cytometry. During
      infection, no increase in IL-2R alpha was observed in either microfilaraemic or
      amicrofilaraemic rats. The PBL of rats were stimulated with phytohaemagglutinin
      (PHA) and the frequency of IL-2R alpha-positivity was examined. After
      microfilariae appeared, the increase in the rate of IL-2R alpha-positivity in
      microfilaraemic rats was less than in amicrofilaraemic rats. The anergy of IL-2R
      alpha expression in microfilaraemic rats was restored when their lymphocytes were
      cultured with normal rat serum. IL-2R alpha expression in normal uninfected rats
      decreased when cultured with serum from microfilaraemic rats. These results
      suggest that microfilariae-related factors in rat serum suppress PHA-induced IL
      2R alpha expression in PBL and thus inhibit cell proliferation and host immunity.

PMID- 9011076
TI  - Induction of surface fluidity in Trichinella spiralis larvae during penetration
      of the host intestine: simulation by cyclic AMP in vitro.
AB  - The lateral diffusion (DL) properties of the fluorescent lipid probe 5-N
      (octadecanoyl) aminofluorescein (AF18) inserted into the surface of muscle-stage
      larvae of Trichinella spiralis were investigated by fluorescence recovery after
      photo-bleaching. AF18 was not free to diffuse laterally in dormant larvae, and
      this remained unchanged after larval activation in vitro with trypsin and bile.
      However, a significant increase in surface fluidity of the probe was demonstrated
      (%R = 74.5; DL = 11.5 x 10(-9) cm2/sec) when larvae invaded intestinal epithelial
      tissue following oral infection of mice. Membrane-permeant photoactivatable caged
      cyclic AMP was used to analyse the putative mechanism responsible for this
      increase in lateral diffusion in the parasite surface. Although incubation of
      larvae with 1-50 microM caged cAMP had no effect on surface fluidity, incubation
      with 100 microM caged cAMP induced a substantial increase in the lateral mobility
      of AF18 (%R = 64.3; DL = 8.3 x 10(-11) cm2/sec) immediately following photo
      activation of the caged messenger. This induced fluidity, however, was transient
      and the larval surface reverted to immobility within 15 min. These observations
      constitute the first reported measurement of the fluid properties of the surface
      of intracellular parasites, the first demonstration of the parasite surface
      fluidity altering as a result of host cell invasion and the first indication of a
      mechanism underlying changes in surface fluidity in parasitic helminths.

PMID- 9011077
TI  - Non-specific binding of mouse IgG1 to Heligmosomoides polygyrus: parasite
      homogenate can affinity purify mouse monoclonal antibodies.
AB  - A characteristic feature of infections with the nematode parasite of mice
      Heligmosomoides polygyrus, is a marked IgG1 hypergammaglobulinaemia. A possible
      source for this immunoglobulin has recently been demonstrated, through evidence
      that H. polygyrus adult worm homogenate (AWH) can induce the in vitro production
      of non-specific IgG1 from mouse lymphocytes. To determine the interactions
      between this immunoglobulin and the parasite, the ability of IgG1 to bind to AWH
      of H. polygyrus was investigated. Protein (Western) blotting indicated that mouse
      monoclonal antibodies are able to bind non-specifically to selected parasite
      antigens. Furthermore, by binding H. polygyrus adult worm homogenate to cyanogen
      bromide (CNBr)-activated Sepharose CL-4B, an affinity column was prepared which
      could be used to efficiently purify mouse IgG1 monoclonal antibodies. These
      antibodies were eluted from the affinity column and still retained their original
      specificity. These results indicate that H. polygyrus not only induces the
      production of non-specific IgG1 by the host, it can also bind this immunoglobulin
      to its own specific proteins. Thus, it is possible that IgG1 produced during a
      primary infection with H. polygyrus may not entirely benefit the host.

PMID- 9011078
TI  - Human Taenia eggs develop into cysticerci in scid mice.
AB  - The intermediate hosts for Taenia saginata and T. solium are cattle and pigs (and
      humans for the latter), respectively. In vitro-hatched (but not activated)
      oncospheres of both Asian Taenia (T. saginata asiatica, a new subspecies of T.
      saginata or T. asiatica, a new species) and T. solium injected subcutaneously
      into the backs of mice with severe combined immunodeficiency (scid) developed
      into fully matured cysticerci. Five-month-old metacestodes of Asian Taenia had no
      hooklets and were bigger in size than those previously reported and similar to
      those of T. saginata. Their morphology suggested that the cysticerci were more
      advanced than those in the intermediate host animals. It is suggested that scid
      mice are valuable experimental animal models for studying human taeniid cestode
      infections.

PMID- 9011079
TI  - Immunoepidemiology of the equine tapeworm Anoplocephala perfoliata: age-intensity
      profile and age-dependency of antibody subtype responses.
AB  - The equine intestinal cestode Anoplocephala perfoliata has been the subject of
      recent epidemiological and immunological studies because of its suspected
      association with intestinal disease in the horse. We have previously shown that
      the IgG(T) subtype antibody response to the 12/13 kDa component of the parasite
      excretory/secretory (E/S) antigen is positively correlated with parasite
      intensity. In this study, we utilize that correlation to examine the changes in
      natural infection intensity with age. Infection intensity based on IgG(T)
      responses showed a triphasic age-dependency pattern with peak mean worm burden in
      the 6 months-2 years age group, falling to a lower plateau level from 3 to 15
      years, and rising again in older age groups. Anti-E/S total IgG was found to have
      a convex age-dependency curve, with maximal response in the 6 months-2 years old
      age group. IgG(a) showed a triphasic response similar to the age-intensity
      profile of IgG(T); IgG(c) showed steadily increasing levels of antibody with age.
      The IgG(b) age-dependency profile was intermediate between IgG(a) and IgG(c). Age
      specific correlation coefficients between anti-12/13 kDa IgG(T) (as a measure of
      infection intensity) and IgG(a) and IgG(b) revealed statistically significant
      values for many age groups. The relative importance of exposure to infection and
      the development of acquired immunity as determinants of the observed age
      intensity pattern is considered.

PMID- 9011081
TI  - The SHOOT MERISTEMLESS gene is required for maintenance of undifferentiated cells
      in Arabidopsis shoot and floral meristems and acts at a different regulatory
      level than the meristem genes WUSCHEL and ZWILLE.
AB  - The function of the SHOOT MERISTEMLESS (STM) gene in shoot and floral meristems
      throughout Arabidopsis development has been analyzed. The results show that STM
      plays a major role in maintaining shoot and floral meristems. In an allelic
      series of stm mutants the shoot meristem was either reduced or completely absent
      in mature embryos and mutant seedling cotyledons showed partial fusion,
      indicating that the STM gene affects embryonic shoot meristem development and
      spacing of cotyledons. Postembryonically, stm mutants initiated adventitious
      shoot development at a position corresponding to the shoot meristem in wild-type.
      Repetitively initiated defective mutant shoot and floral meristems were consumed
      during primordia formation and typically terminated prematurely in fused ectopic
      primordia, indicating that STM is required for continuous shoot and floral
      meristem function. Analogous defects were observed in stm embryonic and
      postembryonic development suggesting that similar mechanisms are employed in
      embryonic and postembryonic organ primordia initiation. Allelic combination
      suggest different thresholds for STM requirement during plant development. STM
      requirement could not be bypassed by standard growth factor regimes or by shoot
      regeneration from calli. The results suggest that STM functions by preventing
      incorporation of cells in the meristem center into differentiating organ
      primordia and that this role can completely account for all defects observed in
      stm mutants. Mutations in the WUSCHEL (WUS) and ZWILLE (ZLL) genes result in
      defective organization and premature termination of shoot meristems. Genetic
      interactions between STM, WUS and ZLL were analyzed and the results indicate that
      STM acts upstream of WUS and ZLL. Therefore, while STM appears to function in
      keeping central meristem cells undifferentiated, WUS and ZLL seem to be
      subsequently required for proper function of these cells.

PMID- 9011080
TI  - The promoter of a H2O2-inducible, Arabidopsis glutathione S-transferase gene
      contains closely linked OBF- and OBP1-binding sites.
AB  - Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that
      play critical roles in the detoxification of xenobiotics and the protection of
      tissues against oxidative damage. GSTs are important enzymes in plant responses
      to a number of environmental stresses including herbicides and pathogen attack.
      Ocs elements are a group of related, 20 bp promoter elements which have been
      exploited by some plant pathogens to express genes in plants. Ocs elements have
      also been found to regulate the expression of a plant GST promoter. An
      Arabidopsis GST gene, called GST6 has been isolated. GST6 expression is under
      tissue-specific control and is induced following treatment with auxin, salicylic
      acid and H2O2. The GST6 promoter contains a binding site for two Arabidopsis ocs
      element binding factors (OBF), that has some sequence homology to ocs element
      sequences. Interestingly, OBP1 (OBF binding protein), a DNA-binding protein that
      was isolated by screening an Arabidopsis cDNA library with a labeled OBF protein
      as a probe, binds next to the OBF-binding site on the GST6 promoter. OBP1 was
      able to significantly stimulate the binding of OBF proteins to the GST6 promoter,
      raising the possibility that interactions between the OBP1 and OBF proteins may
      be important for GST6 expression.

PMID- 9011083
TI  - The GURKE gene is required for normal organization of the apical region in the
      Arabidopsis embryo.
AB  - Dicot plant embryos undergo a transition from radial to bilateral symmetry. In
      Arabidopsis, this change reflects patterning within the apical region, resulting
      in the formation of the cotyledon and shoot meristem primordia. Mutations in the
      GURKE gene give seedlings with highly reduced or no cotyledons. Both strong and
      weak gurke alleles confer this phenotypic variability although strong alleles
      often eliminate the entire apex and sometimes also part of the hypocotyl. The
      root and the root meristem as well as the radial pattern of concentric tissue
      layers are essentially normal. The mutant seedling phenotype can be traced back
      to the triangular/early-heart stage of embryogenesis when abnormal cell divisions
      occur within the apical region such that no or only rudimentary cotyledon
      primordia are established. The postembryonic development of gurke seedlings was
      examined in culture. In weak alleles, apical growth gave rise to abnormal leaves
      and stem-like structures and, eventually, abnormal flowers. In strong alleles,
      the apical region often failed to grow but occasionally produced fused leaf-like
      structures with no dorso-ventral polarity and a totally unorganized vascular
      system while no stems developed. The observations suggest that the GURKE gene is
      involved primarily in the organization of the apical region in the embryo and may
      also play a role during postembryonic development.

PMID- 9011082
TI  - Cloning and functional analysis of a cDNA encoding a novel 139 kDa starch
      synthase from potato (Solanum tuberosum L.).
AB  - Three isoforms of starch synthase were shown to be present in soluble potato
      tuber extracts by activity staining after native gel electrophoresis. An antibody
      directed against a domain conserved in starch synthases was used to clone a cDNA
      for one of these isoforms by screening a tuber-specific expression library. A
      partial cDNA of 2.6 kbp was obtained and used to isolate a full-length cDNA of
      4167 bp. The deduced amino acid sequence identifies the protein as a novel type
      of starch synthase from potato with a molecular mass of 139.2 kDa for the
      immature enzyme including its transit peptide. This novel isoform was designated
      SS III. An analysis of the expression pattern of the gene indicates that SS III
      is equally expressed in tubers of different developmental stages as well as in
      sink and source leaves. In several independent transgenic potato lines, where the
      expression of SS III was repressed using the antisense approach, the activity of
      a specific starch synthase isoform was reduced to non-detectable levels as
      determined through activity staining after native gel electrophoresis. The
      reduction of this isoform of starch synthase leads to the synthesis of a
      structurally modified starch in the transgenic plants: there is a drastic change
      in granule morphology and an increased level of covalently linked phosphate.

PMID- 9011084
TI  - Li(+)-regulated 1-aminocyclopropane-1-carboxylate synthase gene expression in
      Arabidopsis thaliana.
AB  - In Arabidopsis thaliana, 1-aminocyclopropane-1-carboxylate synthase (ACS) is
      encoded by a multigene family consisting of at least five members whose
      expression is induced by hormones, developmental signals, and protein synthesis
      inhibition. Li+, known to interfere with the phosphoinositide (PI) second
      messenger system by inhibiting the activity of inositol-phosphate phosphatases,
      is one of the strongest inducers of ACC synthase activity in plants. Treatment of
      etiolated Arabidopsis seedlings with LiCl results in a rapid induction of the
      ACS5 gene. Also, LiCl represses the cycloheximide (CHX)-induced accumulation of
      the ACS2 mRNA. The effects of Li+ on the expression of ACS5 and ACS2 are
      specific, dose-dependent, and can be reversed by Ca2+ and mimicked by the protein
      kinase inhibitor K-252a. The results suggest that the regulation of some ACS
      genes by various inducers may involve protein kinase activity, which in turn may
      be controlled through an inositol 1,4,5-triphosphate (IP3)-mediated Ca2+
      mobilization. Since plants contain no Li+, the cation appears to unmask pre
      existing biochemical capacity that may be utilized by various unknown transducers
      during plant growth and development.

PMID- 9011085
TI  - Induction of cdc2a and cyc1At expression in Arabidopsis thaliana during early
      phases of nematode-induced feeding cell formation.
AB  - Root-knot and cyst nematodes are plant parasites that induce large multinucleated
      feeding cells in the roots of their hosts. Cytological observations have shown
      that root-knot nematodes induce giant cells by cycles of mitosis without
      cytokinesis whereas cyst nematodes provoke cell wall degradation leading to the
      formation of a large syncytium. This study was intended to characterize and
      compare the ability of both types of nematodes to induce progression through the
      cell cycle. For this purpose, the expression, upon nematode infection, of two
      cell cycle markers was followed: a marker for division competence, the cyclin
      dependent kinase cdc2a and a marker for the G2 phase, the mitotic cyclin cyc1At.
      For both types of nematodes, transcriptional activation of these markers was
      correlated with early phases of feeding cell development. Using molecular
      markers, it was thus possible to confirm and extend the observations of repeated
      mitosis in root-knot nematode-induced giant cells. Surprisingly, promoter
      activation of both cdc2a and cyc1At markers was also found upon cyst nematode
      infection, in feeding cells in which mitosis has not been clearly reported.
      Incorporation of tritiated thymidine in these syncytia confirms that they
      progress through the S phase of the cell cycle. One possibility is that cyst
      nematodes induce cycles of DNA endoreduplication shunting the M phase. Despite
      obvious differences in ontogeny, common molecular mechanisms, involving cycles of
      DNA endoreduplication and cdc2a and cyc1At expression, might thus be involved in
      the formation of a giant cell or a syncytium.

PMID- 9011086
TI  - Purification of the Chlorella HUP1 hexose-proton symporter to homogeneity and its
      reconstitution in vitro.
AB  - A prokaryotic biotin acceptor domain was fused to the carboxy terminal end of the
      Chlorella hexose-proton symporter. The plant symporter is biotinylated in vivo
      when expressed in Schizosaccharomyces pombe. The extended biotinylated transport
      protein is fully active, catalyzes accumulation of D-glucose analogs and restores
      growth of a glucose-uptake-deficient yeast strain. Crude membranes were
      solubilized with octyl-beta-D-glucoside in the presence of Escherichia coli L
      alpha-phosphatidylethanolamine. Biotinylated symporter was purified to
      homogeneity by biotinavidin affinity chromatography. The symporter protein was
      reconstituted together with cytochrome-c oxidase prepared from beef heart
      mitochondria into proteo-liposomes. Cytochrome-c oxidase is a redox-driven H(+)
      pump generating a proton motive force (inside negative and alkaline) while
      transferring electrons from cytochrome-c to oxygen; this energy is used by the
      symporter to accumulate D-glucose at least 30-fold. In the absence of the driving
      force the transport protein facilitates diffusion of D-glucose until the
      concentration equilibrium is reached. It was shown that maximal transport
      activity depends highly on the amount of co-reconstituted cytochrome-c oxidase
      and that the symporter possesses 10% of its in vivo turnover number under
      optimized in vitro transport conditions.

PMID- 9011087
TI  - Control of ionic currents in guard cell vacuoles by cytosolic and luminal
      calcium.
AB  - Activity of vacuolar ion channels can be regulated by the cytosolic free Ca2+
      concentration ([Ca2+]cyt). Using the whole-vacuole mode of patch-clamp with Vicia
      faba guard cell vacuoles, three distinct cation currents were apparent that were
      differentially regulated by [Ca2+]cyt. At 'zero' to 100 nM [Ca2+]cyt,
      instantaneous currents typical of Fast Vacuolar (FV) channels were activated. A
      10 fold KCl gradient directed out of the vacuole increased FV currents (up to
      fivefold) at negative potentials compared with the currents in symmetrical KCl.
      At [Ca2+]cyt higher than 100 nM, instantaneous currents became smaller and
      voltage-independent (non-rectifying) and were typical of Vacuolar K(+)-selective
      (VK) channels. These currents were less sensitive to a KCl gradient than were the
      FV currents, being stimulated less than twofold at negative potentials. Reversal
      potentials measured in the presence of a KCl gradient indicated a high K+
      permeability of both FV and VK currents. At [Ca2+]cyt higher than 600 nM time
      dependent currents elicited by positive potentials were typical of Slow Vacuolar
      (SV) channel activation. When the Ca2+ mole fraction in the cytosolic or luminal
      solution was varied the reversal potential of SV currents (determined by tail
      current analysis) passed through maximum or minimum values. The resultant
      calculated apparent permeability ratios varied with ionic conditions but
      indicated high Ca2+ and K+ permeabilities. If a Cl- permeability was assumed then
      the apparent PCa was lower. However, substitution of Cl- by the larger
      (impermeant) anion gluconate had no effect on the reversal potential of SV tail
      currents in the presence of Ca2+ and a K+ gradient, demonstrating that the
      assumption of Cl- permeability of the SV channel is invalid. Single-channel SV
      currents also decreased with increasing cytosolic Ca2+ mole fraction. These data
      indicate that the SV channel is highly cation selective, shows characteristics
      typical of a multi-ion pore and derives ion selectivity by Ca2+ binding. The SV
      channel currents could also be Mg(2+)-activated and were demonstrated to be
      Mg(2+)-permeable in the absence of Ca2+. The apparent permeability ratio (PMg:PK)
      also varied under different ionic conditions. The results indicate not only that
      FV, VK and SV channels are all present in a single cell type, but also that each
      is differentially regulated by [Ca2+]cyt. The respective roles of these channels
      in vacuolar ion release are discussed, and possible conditions are presented in
      which these channels could be activated by disparate signalling pathways during
      stomatal closure.

PMID- 9011088
TI  - Distribution of tobamovirus movement protein in infected cells and implications
      for cell-to-cell spread of infection.
AB  - The intercellular and intracellular distribution of the movement protein (MP) of
      the Ob tobamovirus was examined in infected leaf tissues using an infectious
      clone of Ob in which the MP gene was translationally fused to the gene encoding
      the green fluorescent protein (GFP) of Aequorea victoria. In leaves of Nicotiana
      tabacum and N. benthamiana, the modified virus caused fluorescent infection sites
      that were visible as expanding rings. Microscopy of epidermal cells revealed
      subcellular patterns of accumulation of the MP:GFP fusion protein which differed
      depending upon the radial position of the cells within the fluorescent ring.
      Punctate, highly localized fluorescence was associated with cell walls of all of
      the epidermal cells within the infection site, and apparently represents
      association of the fusion protein with plasmodesmata; furthermore, fluorescence
      was retained in cell walls purified from infected leaves. Within the brightest
      region of the fluorescent ring, the MP:GFP was observed in irregularly shaped
      inclusions in the cortical regions of infected cells. Fluorescent filamentous
      structures presumed to represent association of MP:GFP with microtubules were
      observed, but were distributed differently within the infection sites on the two
      hosts. Within cells containing filaments, a number of fluorescent bodies, some
      apparently streaming in cytoplasmic strands, were also observed. The significance
      of these observations is discussed in relation to MP accumulation, targeting to
      plasmodesmata, and degradation.

PMID- 9011089
TI  - Identification of a salicylic acid-responsive element in the promoter of the
      tobacco pathogenesis-related beta-1,3-glucanase gene, PR-2d.
AB  - The tobacco pathogenesis-related PR-2d gene encodes an acidic beta-1,3-glucanase.
      Expression of the PR-2d: uidA(GUS) chimeric gene is induced in leaves undergoing
      the hypersensitive resistance response to tobacco mosaic virus and after
      treatment with salicylic acid (SA), a chemical believed to play an important
      role(s) in disease resistance. We have constructed transgenic tobacco plants
      which carry various segments of the PR-2d promoter fused to a heterologous core
      35S promoter driving the uidA(GUS) reporter gene. Their analysis indicates that
      sequences from -364 to -288 upstream of the PR-2d transcription start site confer
      a high level of activation by SA (20-fold). Mutations within this sequence,
      located between -339 and -333, depressed SA activation. This region is also
      required for the SA-inducibility of a truncated PR-2d:GUS chimeric gene.
      Contained within this region is a 25 bp element located between -348 and -324
      which was specifically recognized by nuclear factors from tobacco leaves. No
      conclusive differences were observed in the ability of proteins in nuclear
      extracts from water-treated versus SA-treated plants to bind to this cis element
      in vitro.

PMID- 9011090
TI  - The pef mutants of Arabidopsis thaliana define lesions early in the phytochrome
      signaling pathway.
AB  - In a screen for early-flowering mutants, a number of mutants that were early
      flowering under both short and long days were isolated. One such mutant, pef1,
      was selectively insensitive to both red and far-red light in the inhibition of
      hypocotyl elongation response; a classic phytochrome phenotype mediated by both
      PHYA and PHYB. The pef1 mutant seedlings could not be phenotypically rescued by
      biliverdin, a precursor of the phytochrome chromophore, nor did they fail to
      complement any previously identified elongated hypocotyl (hy) mutants. Difference
      spectra and Western blot analysis showed normal concentrations of PHYA
      photoreceptor apoprotein, which appeared photochemically active. It was concluded
      that the pef1 mutant is defective in both PHYA- and PHYB-mediated signaling
      pathways, and may represent a lesion in an early step of the phytochrome signal
      transduction pathway. Additional pef mutants deficient specifically in PHYB
      mediated responses were also identified by this screen.

PMID- 9011091
TI  - Molecular cloning of a carotenoid-associated protein from Cucumis sativus
      corollas: homologous genes involved in carotenoid sequestration in chromoplasts.
AB  - Chromoplasts are carotenoid-accumulating plastids found in the corollas and
      fruits of many higher plants. In most cases, the pigment in these plastids is
      accumulated with the aid of carotenoid-associated proteins located within unique
      structures. This paper reports the isolation and characterization of the cDNA
      (CHRC) from Cucumis sativus corollas which encodes the chromoplast-specific
      carotenoid-associated protein CHRC. The transit peptide cleavage site was
      determined and, using a chloroplast uptake system, it is shown that CHRC can be
      post-translationally targeted to these plastids where it is peripherally
      associated with thylakoids. Analysis of CHRC transcript level in Cucumis sativus
      revealed its temporal and tissue-specific regulation: the transcript was detected
      only in corollas, where its level increased in parallel to flower development,
      peaking just before anthesis. CHRC shares significant homology (59%) with the
      gene coding for fibrillin-a protein in Capsicum annuum red fruits whose function
      is essentially identical to that of CHRC. A CHRC fragment including the potential
      active site of the protein was used as a probe in Northern blot analyses of
      floral and fruit tissues from various plants containing chromoplasts of different
      types: CHRC homologs of similar sizes were revealed in all cases. The existence
      of a group of homologous genes coding for chromoplast-specific proteins which aid
      in the sequestration of carotenoids within specific structures is proposed.

PMID- 9011092
TI  - Isolation and characterization of a cDNA encoding mitochondrial chaperonin 10
      from Arabidopsis thaliana by functional complementation of an Escherichia coli
      groES mutant.
AB  - Chaperonin (Cpn) is one of the molecular chaperones. Cpn10 is a co-factor of
      Cpn60, which regulates Cpn60-mediated protein folding. It is known that Cpn10 is
      located in mitochondria and chloroplasts in plant cells. The Escherichia coli
      homologue of Cpn10 is called GroES. A cDNA for the Cpn10 homologue was isolated
      from Arabidopsis thaliana by functional complementation of the E. coli groES
      mutant. The cDNA was 647 bp long and encoded a polypeptide of 98 amino acids. The
      deduced amino acid sequence showed approximately 50% identity to mammalian
      mitochondrial Cpn10s and 30% identity to GroES. A Northern blot analysis revealed
      that the mRNA for the Cpn10 homologue was expressed uniformly in various organs
      and was markedly induced by heat-shock treatment. The Cpn10 homologue was
      constitutively expressed in transgenic tobaccos. Immunogold and immunoblot
      analyses following the subcellular fractionation of leaves from transgenic
      tobaccos revealed that the Cpn 10 homologue was localized in mitochondria and
      accumulated at a high level in transgenic tobaccos.

PMID- 9011093
TI  - The rosette habit of Arabidopsis thaliana is dependent upon phytochrome action:
      novel phytochromes control internode elongation and flowering time.
AB  - A major function of phytochromes in light-grown plants involves the perception of
      changes in the relative amounts of red and far-red light (R:FR ratio) and the
      initiation of the shade-avoidance response. In Arabidopsis thaliana, this
      response is typified by increased elongation growth of petioles and accelerated
      flowering and can be fully induced by end-of-day far-red light (EOD FR)
      treatments. Phytochrome B-deficient (phyB) mutants, which have a constitutive
      elongated-petiole and early-flowering pheno-type, do not display a petiole
      elongation growth response to EOD FR, but they do respond to EOD FR by earlier
      flowering. Seedlings deficient in both phytochrome A and phytochrome B (phyA
      phyB), have a greatly reduced stature compared with wild-type or either monogenic
      mutant. The phyA phyB double null mutants also respond to EOD FR treatments by
      flowering early, suggesting the operation of novel phytochromes. Contrary to the
      behaviour of wild-type or monogenic phyA or phyB seedlings, petiole elongation in
      phyA phyB seedlings is reduced in response to EOD FR treatments. This reduction
      in petiole elongation is accompanied by the appearance of elongated internodes
      such that under these conditions the plants no longer display a rosette habit.

PMID- 9011094
TI  - A transcriptional activation domain of ATMYB2, a drought-inducible Arabidopsis
      Myb-related protein.
AB  - Trans-activation activity of ATMYB2, a drought-inducible Myb-related protein in
      Arabidopsis thaliana, was analyzed using a transient assay of Arabidopsis leaf
      protoplasts. ATMYB2 activated the transcription of a reporter gene from the MYB
      binding site in a sequence-specific manner. Deletion of the C-terminal region of
      ATMYB2 reduced the trans-activation of the reporter gene, indicating that the
      acidic region at the C-terminus of ATMYB2 is required for transcriptional
      activation. The domain exchange analysis with the yeast GAL4 revealed that the C
      terminal acidic region of ATMYB2 contains a sufficient domain for trans
      activation. These results indicate that ATMYB2 acts as a transcriptional
      activator and that the C-terminal acidic region of ATMYB2 can function as a
      transcriptional activation domain.

PMID- 9011095
TI  - Calcium and cGMP target distinct phytochrome-responsive elements.
AB  - Previous work using microinjection into single cells of the tomato aurea mutant
      demonstrated that phytochrome A-dependent activation of rbcS and chs genes was
      mediated by calcium and cGMP, respectively. This work sought to identify promoter
      cis-elements that respond to these two small molecules. Box II and Unit I,
      derived from rbcS-3A and chs promoters, respectively, were previously shown to
      function as light-responsive cis-elements. Eleven copies of Box II and four
      copies of Unit I were linked 5' to the -90 and -46 35 S promoters, respectively,
      and, both constructs were fused to the beta-glucuronidase (GUS) reporter gene.
      GUS activities were obtained upon coinjection of either Box II/-90GUS or Unit I/
      46GUS with oat phytochrome A (phyA) and GTP gamma S, an activator of
      heterotrimeric G proteins. The activation of Box II/-90GUS by phyA was
      insensitive to the cGMP antagonist, Rp-cGMPS, although anthocyanin accumulation,
      but not chloroplast development, was totally blocked in the injected cells.
      Consistent with this result, calcium, but not cGMP, induced Box II/-90GUS
      activity. In contrast to Box II/-90GUS, phyA-dependent activation of Unit I/
      46GUS activity was blocked by Rp-cGMPS. Moreover, cGMP, not calcium, induced Unit
      I/-46GUS activity. Control experiments showed that -90 GUS and -46 GUS were
      inactive in the presence of calcium and cGMP, respectively. These results provide
      evidence that Box II and Unit I are targets of the calcium and cGMP pathways,
      respectively. Interestingly, calcium activation of Box II/-90GUS was repressed by
      a high concentration of cGMP and cGMP induction of Unit I/-46GUS was blocked by a
      high concentration of calcium/CaM. Thus, these two small cis-elements can also
      serve as targets of the reciprocal control mechanisms that operate to regulate
      the activities of the two phyA signaling branches.

PMID- 9011096
TI  - fhy1 defines a branch point in phytochrome A signal transduction pathways for
      gene expression.
AB  - Physiological analysis of the fhy1 mutant of Arabidopsis has led to the proposal
      that the mutant is deficient in a downstream component of the phytochrome A
      signal transduction pathway. To define this lesion at the molecular level, we
      have examined the expression of a range of phytochrome-regulated genes in fhy1.
      In far-red light, the regulation of genes such as CHS and CHI is blocked in fhy1,
      whereas the induction of CAB and NR genes is affected minimally. In contrast, the
      induction of all genes tested is blocked in a phytochrome A-deficient mutant,
      confirming that gene expression in far-red light is regulated solely by
      phytochrome A. Thus, fhy1 defines a branch point in phytochrome A signal
      transduction pathways for gene expression. Contrary to the general opinion that
      responses to continuous red light are mediated by phytochrome B and other
      photostable phytochromes, we have shown also that red light-induction of CHS is
      mediated almost entirely by phytochrome A. Furthermore, phytochrome A-mediated
      induction of CHS by red light is blocked in fhy1. The induction of CHS by blue
      light, however, is normal in fhy1, suggesting that although FHY1 is a component
      of the phytochrome A signaling pathway, it is not a component of the blue-light
      signaling pathway for CHS expression.

PMID- 9011098
TI  - Immunofluorescent quantitation of chloroplast proteins.
AB  - Using scanning light microscopy software to detect and measure immunofluorescence
      in leaf sections Rubisco concentration in situ in chloroplasts has been
      accurately determined throughout development. The fluorescence measurements were
      calibrated by comparison with values for Rubisco accumulation obtained from
      rocket immuno-electrophoresis profiles of soluble protein from isolated cells and
      from chloroplasts using a purified sample of Rubisco as the standard. It has been
      shown that in situ immunofluorescence can be used for cytoquantitation of
      proteins within individual chloroplasts to a sensitivity of 1fg and also for the
      comparison of the protein levels in adjacent chloroplasts and cells. Several
      important applications of this new technique are discussed.

PMID- 9011097
TI  - Gene identification in a complex chromosomal continuum by local genomic cross
      referencing.
AB  - Most higher plants have complex genomes containing large quantities of repetitive
      DNA interspersed with low-copy-number sequences. Many of these repetitive DNAs
      are mobile and have homology to RNAs in various cell types. This can make it
      difficult to identify the genes in a long chromosomal continuum. It was decided
      to use genic sequence conservation and grass genome co-linearity as tools for
      gene identification. A bacterial artificial chromosome (BAC) clone containing
      sorghum genomic DNA was selected using a maize Adh1 probe. The 165 kb sorghum BAC
      was tested for hybridization to a set of clones representing the contiguous 280
      kb of DNA flanking maize Adh1. None of the repetitive maize DNAs hybridized, but
      most of the low-copy-number sequences did. A low-copy-number sequence that did
      cross-hybridize was found to be a gene, while one that did not was found to be a
      low-copy-number retrotransposon that was named Reina. Regions of cross
      hybridization were co-linear between the two genomes, but closer together in the
      smaller sorghum genome. These results indicate that local genomic cross
      referencing by hybridization of orthologous clones can be an efficient and rapid
      technique for gene identification and studies of genome organization.

PMID- 9011099
TI  - A plant in vitro system for the nuclear import of proteins.
AB  - This paper reports the development of an in vitro system that allows the direct
      assay of protein import into plant nuclei. In this assay the import of
      fluorescently labelled karyophilic protein substrates into nuclei isolated from
      evacuolated tobacco BY-2 suspension cells is monitored. It is demonstrated that
      import of the fluorescently labelled peptide conjugates is rapid, saturable and
      nuclear localization signal (NLS)-dependent. Exclusion of high molecular weight
      (70 kDa) dextran and substrates carrying mutated NLS sequences further underline
      the specificity of this system. Nuclear translocation of karyophilic import
      substrates in tobacco, similar to mammalian systems, is inhibited by the non
      hydrolysable GTP analogue GTP-gamma-S. In contrast, protein uptake is not blocked
      by wheat germ agglutinin, N-ethyl-maleinimide and iodoacetic acid. Furthermore,
      it is shown that nuclear import of proteins is only partially inhibited by low
      temperature (0-4 degrees C). The in vitro nuclear import assay does not depend on
      exogenously added ATP or cytosolic factors. However, a block of nuclear import
      with GTP-gamma-S could be overcome by the addition of cytosolic extract,
      suggesting the dependence on cytosolic factors or proteins. These data indicate
      that the characteristics of nuclear protein import in plant and mammalian cells
      are similar, but may be, at least in some respects, also different from each
      other.

PMID- 9011100
TI  - Use of monoclonal antibodies for immunohistochemical study of bovine spleen on
      frozen sections.
AB  - Many monoclonal antibodies reactive with bovine leukocyte differentiation
      antigens are now available. Immunohistochemical staining on frozen sections using
      these monoclonal antibodies permits study of the functional morphology of bovine
      spleen. This study confirms accepted notions (B and T dependent-zones) and
      supplies complementary data about the repartition of CD4 and CD8 cells, gamma
      delta T cells, MHC (Major Histocompatibility Complex) II expression, and
      macrophages.

PMID- 9011101
TI  - Ultrastructure of pre- and postcolostral enterocytes of the newborn calf.
AB  - Ten calves were used to elucidate the ultrastructure of enterocytes before and 24
      h after colostral intake. Tissue samples were obtained from duodenum, jejunum (5
      locations) and ileum. Protein A-gold technique was applied to immunoelectron
      microscopically demonstrate colostral IgA. The prominent feature of the
      precolostral enterocytes are intracytoplasmic vacuoles. The frequency of vacuoles
      increases from cranial jejunum to ileum and from the villi bases to the tips. The
      appearance of absorptive vacuoles after colostral administration correlates with
      the incidence of precolostral empty vacuoles. Bovine IgA was detected in
      absorptive vacuoles and within the intestinal lumen of postcolostral calves. In
      addition to a diffuse IgA labelling of most vacuoles, a few corresponding
      enterocytic vacuoles labelled inhomogenously or negatively. This study
      demonstrates morphologically that the main site of colostral absorption is the
      middle-to-caudal region of the small intestine. Immunoelectron microscopy of IgA
      labelling provides indications of a selective IgA absorption in addition to
      pinocytosis.

PMID- 9011102
TI  - Basket and basal-duct cells in domestic animals: different cytokeratin expression
      and shape.
AB  - Cytokeratins (CKs) are a multigenic family of proteins constituting intermediate
      filaments in epithelia, indicated in humans by the numbers 1-20. Different cell
      types can be immunocytochemically identified on the grounds of their CK
      expression. This investigation was designed to study CK expression of basket
      cells (BCs) and basal-duct cells (BDCs) in some domestic animals. Frozen sections
      of mammary and major salivary glands from cows, sheep, pigs and rabbits were
      treated using the immunofluorescent method, using as monoclonal antibodies clones
      CK-E3, CKB1, KS-1A3, and LDS-68, respectively, revealing the human CKs 17, 14,
      13, 7. BCs surrounding acini and BDCs were stained by CK 17 antibody only in the
      rabbit. CK 14 was detectable in both cell types in cows, sheep and pigs, except
      in the case of bovine salivary BCs. CK 13 was revealed in BCs and BDCs of all
      mammary glands and also rabbit salivary glands. In the salivary glands of the
      other species, only BDCs were stained. CK 7 gave unreliable results in all the
      species and cell types examined. Interestingly, in the rabbit, also BDCs are
      basket-like in shape. The antibodies employed showed different staining depending
      on species and gland. On the grounds of immunoreactivity and shape, BCs and BDCs
      can be considered the same cell type in the rabbit. In the other species, they
      appear to be different, since BDCs may express additional CKs and are triangular
      shaped, whereas BCs are truly basket-like. It is worth noting that clone KS-1A3
      in the rabbit and CKB1 in the sheep and pig can be considered markers of the
      basket/ basal system.

PMID- 9011104
TI  - Intrinsic innervation of the stomach of the fetal pig: an immunohistochemical
      study of VIP-immunoreactive nerve fibres and cell bodies.
AB  - Using an immunohistochemical technique, the presence and distribution of
      vasoactive intestinal polypeptide (VIP) was investigated in cryostat sections,
      both tangential and transverse, of the fetal pig's stomach. In all fetuses and in
      all gastric segments investigated, VIP-like immunoreactive (IR) nerve-cell bodies
      were seen in all intramural ganglia, and VIP-IR nerve fibres were found in all
      layers of the gastric wall except the tunica serosa. Consequently, VIP-IR nerve
      fibres were found to form a periglandular network, to accompany arterioles, to
      interconnect the intramural ganglia, to encircle both VIP-IR-negative and 
      positive neurons, and were found in all muscle layers. Despite the fact that VIP
      IR seems to be restricted to the intramural nervous elements, some non-specific
      reacting VIP-IR glandular cells were noticed in the basal parts of the fundic,
      antral and pyloric gastric glands. The distribution pattern of VIP in the fetal
      pig resembles that of the adult pig. This suggests a possible functional role for
      VIP during fetal life and/or puts forward the suggestion that the stomach of a
      fetal pig from the second half of the gestation period is prepared, from then on,
      for postnatal function. High similarities with regard to the general distribution
      pattern of VIP in the stomach have also been noted between the fetal pig and
      humans, proving once more that the fetal pig can serve as a good animal model in
      several research areas. Finally, the morphological data provided here may,
      combined with the physiological significance of VIP, contribute to a better
      insight into the physiopathology of economically important gastro-intestinal
      disorders in the pig, such as gastric ulceration.

PMID- 9011103
TI  - Demonstration of congenital anomalies in the joints of the forelimbs and
      hindlimbs caused by several pharmacological agents.
AB  - In this study, fetal joint abnormalities caused by cytosine arabinoside,
      caffeine, sodium salicylate, and retinyl acetate administration during pregnancy,
      were investigated. In the cytosine-arabinoside-administered group, complete
      disappearance of joint spaces in the forelimbs, and narrowing or complete
      disappearance of joint spaces in the hindlimbs was highly noticeable. In the
      caffeine group, in all forelimb joints starting from art, humeri, there were
      abnormal fusions in bones, together with occasional disappearance of the joint
      space. In hindlimbs, similar findings were observed. In the sodium salicylate
      group, the complete disappearance of joint space and surfaces among humerus
      radius and ulna was striking, and occasional fusions in tarsometatarsal joints
      were also present. Severe narrowing of the same joint space in the retinyl
      acetate group was striking. Total disappearance of the articulation manus and
      carpometacarpal joints was observed, together with hindlimb joint and bone
      findings.

PMID- 9011105
TI  - Muscle representation within the hypoglossal nucleus of the chicken studied by
      means of horseradish peroxidase.
AB  - The distribution in the chicken of motoneurons innervating the hyolingual
      muscles, i.e. the Mm. hyoglossus rostralis (HR), hyoglossus obliquus (HO),
      ceratoglossus (CG), interceratobranchialis (CB), stylohyoideus (YH),
      serpihyoideus (PH) and cricohyoideus (CR), and the laryngotracheal muscles,
      comprising the Mm. tracheolateralis (TL), cleidohyoideus (CL) and
      sternotrachealis (ST), was examined by retrograde transport of horseradish
      peroxidase conjugated with wheat-germ agglutinin. Labelled motoneurons are only
      found in the hypoglossal nucleus. The rostrocaudal distributions of motoneurons
      projecting to hyolingual muscles are restricted in the hypoglossal nucleus
      cranial to the obex, and those projecting to laryngotracheal muscles are
      distributed in the more caudal part of hypoglossal nucleus. Detailed analysis of
      the data showed that the most rostrally positioned motoneurons in the hypoglossal
      nucleus supplied to the PH, followed by the CG, CB, HR, YH, HO, CR, TL, CL and ST
      in that order, overlapping each other. In the hypoglossal nucleus motoneurons
      innervating the PH and YH have the smallest perikarya. Of the motoneurons in the
      hypoglossal nucleus, those supplying the laryngotracheal muscles (CL and TL) have
      the largest perikarya. Motoneurons innervating the other muscles are intermediate
      in size.

PMID- 9011107
TI  - The coronary arteries of the dromedary camel (Camelus dromedarius).
AB  - The pattern of distribution of the coronary arteries of the camel was studied by
      combining dissection and vinyl acetate casts. The results showed that in the
      camel the right coronary artery supplies the interventricular subsinuosal artery,
      characteristic of a right coronary pattern. The septal branch that supplied the
      interventricular septum originated from the paraconal interventricular artery. A
      muscular bridge was observed crossing each of the paraconal and subsinuosal
      interventricular arteries in the middle third of the longitudinal grooves.

PMID- 9011106
TI  - Detection of coagulating gland renin by hybridohistochemistry.
AB  - To obtain evidence of renin-synthesizing cells in the murine coagulating gland
      (CG), CG renin mRNA was detected by hybridohistochemistry, as well as in vitro
      reverse transcriptase-polymerase chain reaction (RT-PCR) in intact, castrated and
      testosterone-treated C57BL/6 mice. Hybridohistochemistry using paraffin sections
      of the kidneys and the CGs for the detection of renin mRNA was performed with
      digoxigenin-labelled probes. Some paraffin sections were immunohistochemically
      stained for renin by the peroxidase-anti-peroxidase method. Total RNA was
      extracted, incubated by reverse transcriptase, and amplified by PCR. In the
      kidneys, the immunoreactivity and the positive signals of hybridohistochemistry
      using an antisense probe were restricted to the same juxtaglomerular cells. In
      the control and at 7 days after testosterone administration to castrated mice,
      both renin-immunoreactivity and -hybridoreactivity were expressed by the
      epithelial cells in the CGs, while, in the CGs of the castrated mice and 3 days
      after testosterone injection of castrated animals, neither renin-immunoreactivity
      nor -hybridoreactivity was detected in the epithelial cells. Using RT-PCR, renin
      mRNA from the mice in the control and 7 days after testosterone injection of
      castrated was amplified, whereas, in the castrated and the 3 days after
      testosterone injection of castrated groups, it was not detected. The data
      presented here provide additional evidence that CG renin is regulated by
      testosterone.

PMID- 9011108
TI  - Hatching gland cells of trout embryos as the target of positional information.
AB  - HGCs were found in the head epidermis, yolk sac and pharynx epithelium of trout
      embryos. These cells usually appear in clusters, closely related positionally to
      neighbouring cells. The differentiation and specialization of HGCs seem to be
      mainly dependent on cell-cell interactions, which provides, in part, the
      positional information necessary for the cells to differentiate and localize in
      the appropriate place. The final secretory process is the result of a sequence of
      events by which the maturation of enzymatic granules occurs. The electron-density
      of the granules varies according to the proximity of the secretory stage.
      Exocytosis of the secretory granules were observed. After secretion, each HGC
      undergoes cellular death by apoptosis (programmed cell death).

PMID- 9011109
TI  - Secretory protein 7B2 response to oral glucose loading and intravenous glucagon
      injection in patients with diabetes mellitus.
AB  - Serum 7B2 concentrations in control subjects and patients with diabetes mellitus
      were measured following a 75 g oral glucose load and following intravenous
      glucagon infusion. In response to oral glucose, serum 7B2 levels increased in the
      controls (n = 10) and in the diabetic patients (n = 7). The increment of the
      serum 7B2 level was smaller in the diabetic patients than the controls. During
      the 75 g oral glucose tolerance test (75g OGTT), serum 7B2 levels were
      significantly positively correlated with serum C-peptide levels. In contrast,
      following intravenous glucagon infusion, serum 7B2 levels increased only in
      diabetic patients treated with oral hypoglycemic agents (n = 20) and did not
      increase in controls (n = 5): the group having the highest insulin secretion
      activity in the present study, nor in diet or insulin-treated diabetic patients.
      No correlation between serum 7B2 levels and serum CPR levels was observed in the
      intravenous glucagon infusion study. These data suggest that an extra-pancreatic
      source which produces the observed serum 7B2 increase following oral glucose
      intake can not be excluded and that 7B2 may not be secreted concomitantly with
      insulin from the pancreatic beta cell in response to intravenous glucagon
      injection.

PMID- 9011110
TI  - Slowing of ventricular rate quickly improved ventricular dysfunction and exercise
      intolerance in patients with chronic atrial tachycardia.
AB  - Three cases of chronic atrial tachycardia associated with ventricular dysfunction
      and severe exercise intolerance markedly improved within a few weeks when
      ventricular rate was slowed. Slowing ventricular rate may improve symptoms and
      ejection fraction despite possible changes in myocyte and tissue structure.

PMID- 9011111
TI  - [A family of autosomal dominant facio-limb-girdle muscular dystrophy].
AB  - A family of autosomal dominant facio-limb-girdle muscular dystrophy was reported.
      The proband was a 28-year-old male. His father and sister suffered from a similar
      disease. All patients developed weakness of lower limbs and atrophy of thigh at
      second to fourth decades. All showed mild facial and neck flexor weakness as well
      as proximal dominant weakness and atrophy of four limbs. Limb muscle involvement
      was more severe in lower limbs than in upper limbs in all cases. Interestingly,
      all showed limitation of ankle dorsiflexion (tight heel cord), although distal
      muscles of lower limbs were not involved or only mildly involved clinically. On
      laboratory examination, serum CK increased slightly. Needle EMG revealed low
      amplitude, polyphasic MUP in limb muscles in all cases. Biopsied muscles taken
      from the proband showed non-specific myogenic changes. Rimmed vacuoles were not
      observed. Our cases were different from Bethlem myopathy, because the age of
      onset was late and joint contractures were mild in our cases, as compared with
      Bethlem myopathy. Clinical manifestations of our family showed a strong
      resemblance to the family reported by Girchlist et al, but similar cases were not
      reported in Japan.

PMID- 9011113
TI  - [Plasmidic extended spectrum resistance to beta-lactams in nosocomial
      infections].

PMID- 9011112
TI  - [Some unusual severe infections requiring prompt intervention].

PMID- 9011114
TI  - [Detection and genotyping of astroviruses by RT-PCR and sequencing].
AB  - Three primer pairs, AV244Mon and 82b, AV-15Gr and AV-12Gr, and Beg and End, were
      used for the detection of standard astroviruses (serotype 1 to serotype 7) in
      cell culture and astroviruses isolated from 89 diarrheal stool specimens negative
      for pathogenic bacteria, rotavirus and adenovirus by the reverse transcription
      polymerase chain reaction (RT-PCR). All the standard strains and two isolates
      were detected by primer pairs AV244Mon and 82b, and AV-15Gr and AV-12Gr. All
      serotypes except serotype 4 were detected by the primer pair Beg and End. The
      molecular sizes of the RT-PCR products obtained by Beg and End were almost the
      same among the different serotypes except serotype 6. Sequence analyses of the
      nucleic acid in the regions between the primer pairs AV244Mon and 82b, and
      between Beg and End from PCR products of the standard strains and from the
      isolates of the two stool specimens revealed that each serotype had a unique
      sequence. These results indicate that the RT-PCR is useful for detecting and
      genotyping astroviruses.

PMID- 9011115
TI  - [Evolution of susceptibilities of Campylobacter jejuni isolated from diarrhoeal
      cases to fluoroquinolones in Tokyo].
AB  - Recently, the increase in the number of resistant strains of Campylobacter jejuni
      to fluoroquinolone has been reported in European countries. We also studied
      antimicrobial susceptibilities of 600 clinical isolates of Campylobacter jejuni
      isolated during a 6 year period from 1989 through 1994 in four Tokyo Metropolitan
      Hospitals. The susceptibility to 6 antimicrobial agents, norfloxacin (NFLX),
      ofloxacin (OFLX), ciprofloxacin (CPFX), nalidixic acid (NA), erythromycin (EM)
      and tetracycline (TC) were examined. The overall resistant rates were as follows:
      NFLX, 45 strains (7.5%); OFLX, 45 strains (7.5%); CPFX, 44 strains (7.3%); NA, 62
      strains (10.3%); EM, 4 strains (0.6%) and TC, 259 strains (43.2%). The number of
      resistant strains to fluoroquinolones and NA has increased significantly since
      1993 in Japan, but the susceptibility to erythromycin has still remained the same
      level during the past 6 years. The susceptibility to TC was variable, and MICs
      gave a bimobal distribution, as pointed out previously. The resistance pattern of
      NFLX, OFLX, CPFX and NA were observed most frequently in those isolates.

PMID- 9011116
TI  - [Isolation and incidence of Vibrio cholerae from river water].
AB  - The prevalence of Vibrio cholerae contamination in river water derived from 20
      sites of 18 rivers in Kanagawa, Japan, was investigated during a period from July
      to September, 1987, and from one of the 20 sites in August, 1988 and in February,
      1989, V. cholerae non-O1 was found in all samples at concentrations of 0.9-
      >1,400 MPN/100 ml. Higher amounts of the organism were observed in the samples
      from estuaries. V. cholerae O1 was detected in samples collected in August, 1988
      and in February, 1989 at concentrations of 150 MPN/100 ml and 1.5 MPN/100 ml,
      respectively. From 1989 to 1995, water samples were collected monthly from 10
      sites of 10 rivers to detect V. cholerae. V. cholerae O1 and non-O1 were detected
      in 3.6% (30 of 840) and in 61.1% (513 of 840) in the water samples examined,
      respectively. Overall, V. cholerae was found in 62.9% (528 of 840). Both types,
      O1 and non-O1, of organisms were detected in 15 samples. These results indicated
      that river water was contaminated frequently with V. cholerae non-O1 and
      sporadically with V. cholerae O1 throughout the year. Only one strain of V.
      cholerae O1 out of 543 V. cholerae strains was found to be a producer of cholera
      toxin. During these studies, the selectivity of 3 media for V. cholerae O1 was
      evaluated, and PMT agar was found to be the best.

PMID- 9011117
TI  - Effect of recombinant human granulocyte colony-stimulating factor on combination
      therapy with aztreonam and clindamycin for infections in neutropenic patients
      with hematologic diseases.
AB  - The present multicenter study was performed to evaluate the effect of recombinant
      human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy
      using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in
      neutropenic patients with hematologic diseases. Forty-three neutropenic patients
      with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3
      times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The
      clinical efficacy of this regimen was compared to that obtained in 44 febrile
      neutropenic patients, with hematologic diseases, who received only AZT and CLDM
      in a previous study (historical control group). The overall efficacy rate was
      69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control
      group. Although the neutrophil count was significantly increased and C-reactive
      protein tended to be lower in the rhG-CSF group, the daily maximum body
      temperature profiles of the 2 groups were nearly the same. These results suggest
      that rhG-CSF is of little benefit in the treatment of single infectious episodes
      in neutropenic patients, and that appropriate antibiotic therapy is more
      important.

PMID- 9011118
TI  - [Diagnosis of legionellosis by microagglutination test--comparison to indirect
      immunofluorescent antibody method].
AB  - We studied the micro-agglutination method (MAT) for the diagnosis of
      legionellosis. Serum samples were collected from 44 clinically legionellosis
      suspected patients (17 positive with indirect immunofluorescent antibody
      technique [IFA] and 27 IFA negatives) and 20 healthy adults (25-30 years old).
      MAT showed negative results with sera collected from healthy adults and IFA
      negative patients, 8 out of 17 cass of IFA positive patients showed positive
      results in MAT. The remaining 9 cases out of 17 were negative in MAT judging from
      our criteria (1:256 in single serum or fourfold rise to 1:128 in pair sera). MAT
      had good proportion to IFA in samples collected within three weeks after onset of
      each disease. All sera that became positive in MAT were sampled within four weeks
      after onset of each illness. It was noted that MAT was mainly related to IgM
      class antibodies. These relationships must be decided by investigating more cases
      of legionellosis. According to the result of this study, the MAT method was
      thought to be useful for rapid diagnosis of legionellosis.

PMID- 9011119
TI  - [Serum albumin level as a predictor of incidence of febrile episodes and
      mortality in hospitalized geriatric patients].
AB  - To investigate the relationship between serum albumin level and incidence of
      febrile episodes and mortality in the elderly, we studied 748 patients
      hospitalized for over one year. The subjects included 123 males and 355 females
      with a mean age 81.2 years. The average serum albumin level was 3.79 g/dl and
      levels of serum albumin decreased with advancing age. The incidence of febrile
      episodes was 1.8 per year in patients with serum albumin levels over 4.1 g/dl,
      increasing with decline of serum albumin levels. The incidence of febrile
      episodes was 5.3 per year in patients with serum albumin levels under 3.0 g/dl.
      Patients with serum albumin levels under 3.0 g/dl displayed a high incidence of
      febrile episodes irrespective of age. Age adjusted in-hospital mortality was
      40.4% during the observed period in patients with serum albumin levels under 3.0
      g/dl, significantly higher than that of the patients with serum albumin levels
      over 3.1 g/dl. Relative risk of febrile episode and mortality calculated using
      the patients with serum albumin levels over 4.1 g/dl as a control was 2.9 and
      2.1, respectively, in the patients with serum albumin levels under 3.0 g/dl.
      These results indicate that serum albumin level is a simple, but strong,
      predictor of susceptibility of febrile episode and death. Patients with serum
      albumin levels under 3.0 g/dl may constitute a high risk group for febrile
      episode and death.

PMID- 9011120
TI  - [Rapid detection of the hemolysin genes in Aeromonas sobria by the polymerase
      chain reaction].
AB  - The hemolysin of Aeromonas sobria is one of the important virulence factors in
      this organism. Rapid detection and identification test for A. sobria is important
      for early and specific diagnosis of this infectious disease. We evaluated the
      polymerase chain reaction (PCR) for the rapid detection of A. sobria. Two pairs
      of synthetic oligonucleotide primers (ASA1-s and a; AerAAS-s and a) were used in
      PCR technique to detect the different hemolysin genes (ASA1 and aerAAS) in A.
      sobria. The PCR identified 91% of ASA1-positive and 23.4% of aerAAS-positive
      strains in beta-hemolytic A. sobria. Other species of Aeromonas, Plesiomonas
      shigelloides, Vibrio cholerae O1 and V. parahaemolyticus tested were negative in
      the PCR with two pairs of primers. The PCR technique for detection of two
      hemolysin genes suggested the possibility of application of this method for
      detection of A. sobria in A. sobria-associated infections.

PMID- 9011121
TI  - [Pillin structural gene and bacterial adhesion to cultured cell of Pseudomonas
      aeruginosa isolated from clinical materials].
AB  - Thirty-three stocks of Pseudomonas aeruginosa which is an important etiologic
      agent of opportunistic infections were clinically isolated. The pillin structural
      gene pilA of the stocks were amplified by polymerase chain reaction (PCR) and
      classified into 3 groups; 2000 bp (16 stocks; 48.5%), 1300 bp (11 stocks; 33.3%),
      550 bp (6 stocks; 18.2%). The adhesiveness of the stocks to cultured human lung
      cancer origin calu-1 was also determined, their adhesion rate per cell were
      39.2%, 24.8%, 22.1% in average respectively. Thus clinically most common 2000 pb
      group is remarkably easier to adhere to calu-1. Serotypes of the strains were
      examined to reveal the difference of the distribution that F. G. I types were
      dominant in 2000 pb group, but E types were major in 1300 bp and 550 bp groups.
      These data suggest that the gene arrangement of pilA influences adhesiveness to
      cultured cell and antigenicity of bacteria.

PMID- 9011122
TI  - [A SLE case with toxic shock syndrome after delivery].
AB  - We experienced a SLE patient with TSS after delivery. A 32-year-old SLE patient
      was transferred to our division due to fever, diarrhea, erosive rash, pericardial
      effusion, myalgia, low blood pressure, thrombocytopenia and hypoproteinemia which
      appeared two days after transvaginal delivery. At the time of admission, we
      considered these symptoms as the exacerbation of SLE, and treatment with high
      doses of steroid was started. It was when TSST-1-producing-MRSA was cultured from
      the vagina and uterus that TSS was suspected. 2 g/day of vancomycin was
      administered and her symptoms improved. As observed in this case, it is important
      to consider TSS as one of the complications seen with SLE patients after
      delivery.

PMID- 9011123
TI  - [Detection of DNA specific for Aspergillus species in serum samples from two
      patients with invasive pulmonary aspergillosis].
AB  - We investigated the possible presence of DNA specific for Aspergillus species in
      serum samples of two patients who were strongly suspected for invasive pulmonary
      aspergillosis (IPA) by a nested polymerase chain reaction (PCR) method. Both
      patients were diagnosed as having acute myelogenous leukemia and treated with
      induction chemotherapy. During chemotherapy-induced granulocytopenia, they
      complained of high fever, and the chest X-rays indicated infiltration shadows in
      their lungs. They were treated with antibiotics intravenously, but no clinical
      improvement was observed. As the results of the nested PCR were positive at the
      acute stage of infection, amphotericin B i.v. and granulocyte colony stimulating
      factor s.c. administrations were started in both cases. In case 1, the infectious
      disease improved and the nested PCR results turned negative after treatment. In
      case 2, in spite of the progression of the disease, the nested PCR results turned
      negative during treatment. Although we consider this method very useful for the
      diagnosis of IPA, further prospective evaluation with a large clinical population
      sample is required.

PMID- 9011124
TI  - [Air pollution and its health effects on residents in Taiwanese communities].
AB  - The are a number of particular features of air pollution in Taiwan, as described
      below: (1) In Taiwan area, the air load of pollutants is more serious than
      previously reported. (2) There exists severe air pollution throughout the island.
      (3) Industry is the major source of pollution. (4) No demarcation exists between
      plants and residential quarters. (5) There is a high concentration of pollutants
      indoors/outdoors. The influence of air pollution spreads over all aspects of
      physical health, primarily on the respiratory tract, causing lung cancer and
      exaggerating cardiovascular diseases. A few Taiwanese studies are reviewed below
      which deserve more elaboration. (1) Use PM10 for indexing health effect. The
      annual average value of PM10 in Taiwan has been around 70 micrograms/m3 in 1994.
      Dr. Schwarz indicated that no safety margin could be derived; for each additional
      10 micrograms/ m3 of PM10, the death number could be increased by 1% on the basis
      of Western studies. (2) Research with reference to lung cancer cases in the
      Kaohsiung Medical College Hospital. Living within 3 km of industrial district
      counted for 9% of cases and caused a 6-fold increase in the risk of disease for
      people living more than 20 years in the case control study for lung cancer. (3)
      Death due to cancer of inhabitants close to petroleum and petrochemical
      industries. For youths and children below 20 years, cancers related to brain
      tumors were 2-4 fold of what was expected deaths. Analysis of another
      petrochemical complex in Chienchen, Kaohsiung, revealed the inhabitants within 1
      km showed a higher standardized mortality ratio for cancers of the lung, kidney,
      urinary bladder, and leukemia than was to be expected. (4) Lower lung function
      and higher incidence of respiratory diseases among residents near a coal-fired
      power plant (within 3 Km) compared to residents who lived further away from the
      plant (3-11 Km). (5) Lead contamination around a kindergarten near a battery
      recycling plant. There was increased lead absorption among children of the
      exposed kindergarten and its this was associated with the extent of air and soil
      pollution in the surrounding area. In considering above limited epidemiologic
      evidence, the following recommendations are presented: (1) to conduct
      investigation promptly for the correlation of air pollution to disease morbidity
      and death of inhabitants of Taiwan. (2) to reevaluate ambient air quality
      standards on the basis of Taiwanese health studies. (3) to assess the analytical
      data of past records on the concentrations of air pollutants. (4) collection of
      surcharge fee for air pollution. (5) Regulation for compensation of pollution
      victims among industry. (6) development of environmental health related
      industries. (7) Participation of various parties who are concerned the
      environmental health. One thing is certain, everyong would be able to breath air
      which, as far as possible, is clean.

PMID- 9011125
TI  - [Job strain and drinking behavior].
AB  - The aim of this survey study was to explore the influence of work on individual's
      drinking behavior. From October 1994 to March 1995, the present researchers
      implemented a self-administered questionnaire survey on workers in the
      manufacturing sector in Metropolitan Kaohsiung area, southern Taiwan. Of the
      1,117 subjects selected, 668 (61.8%) stated that they had had one or more drinks
      during the preceding month. The average daily consumption of alcohol was 0.2 +/-
      0.9 drinks (with a range of 0 to 12 drinks and a median of 0.02 drinks). In
      addition, 188 (28.8%) of the subjects reported having experienced drinking
      related problems during the preceding month, and 35 respondents (5.2%) gave
      escape from job stress as the reason for their drinking in the preceding month.
      The result of multivariate analyses showed that workers who reported less
      autonomy in their job were more likely to experience drinking-related problems
      (odds ratio [OR] = 1.3) and to drinking for psychological relief (OR = 1.2); that
      workers who reported more demanding job conditions were more likely to drink for
      escape (OR = 2.5) but had lower levels of drinking (t = -2.5, p = 0.01); and that
      workers who reported high levels of job strain were more likely to experience
      drinking-related problems and to drink for relief but had lower levels of
      drinking. The details and implications of this result will be discussed.

PMID- 9011126
TI  - [Difference in prolaction response of schizophrenic patients to equivalent doses
      of haloperidol, remoxipride and sulpiride].
AB  - Clinically, most of the schizophrenics usually are treated with neuroleptics.
      This kind of medicine increases the prolactin level in serum that causes sexual
      dysfunction. In this study, 27 schizophrenics were divided into three groups.
      After discontinuation of taking the prior medicine for more than two weeks,
      subjects were treated respectively with fixed doses of haloperidol (20 mg),
      remoxipride (450 mg), and sulpiride (1800 mg). During hospitalization, an
      assigned senior resident used Nancy O. Andresen's Scale for the assessment of
      Positive Symptoms (SAPS) and Negative Symptoms (SANS) as tools to categorize
      schizophrenic subjects into subtypes, and another senior resident evaluated the
      effectiveness of the treatment once a week with the Brief Psychiatric Rating
      Scale (BPRS). Prolactin level in serum was monitored weekly with fluorescent
      assay. The Generalized Estimating Equation-I was utilized to analyze the data.
      The results show that all of the three medicines cause elevation of prolactin
      level in serum, and sulpiride causes the highest elevation of prolactin level in
      this study. There is no difference between the subtype of schizophrenia and
      prolactin reaction. There is also no correlation between the degree of elevation
      in prolactin and the effectiveness of treatment. However, there is a
      statistically significant difference in the serum levels between genders. After
      being treated with antipsychotics, female patients are more likely than male
      patients to have an elevated prolactin serum level. In conclusion, this study
      suggests that physicians should be more cautious while treating female psychotic
      patients with sulpiride.

PMID- 9011127
TI  - [Comparison between of TRISS and ASCOT methods--in Tainan area. Trauma and Injury
      Severity Score. A Severity Characterization of Trauma].
AB  - In this study, we compare the Trauma and Injury Severity Score (TRISS) and A
      Severity Characterization of Trauma (ASCOT) models by using NCKUH trauma registry
      to assess the performance of correct prediction in terms of sensitivity,
      specificity and misclassification rate. The database has accumulated to 5,672
      cases, NCKUH 2,490; Chi-Mei 3,182 respectively. Blunt trauma mechanism was
      composed of 4, 892 (86.2%) while 552 (9.7%) were pertinent to penetrating. The
      male/female ratio is 2.4:1. Traffic accident is the major cause of injury (3, 472
      (61.2%)), followed by work injury (723-(12.7%)); fall (702-(12.4%)) and burn
      injuries (160-(2.8%)). The category of traffic accident is comprised of
      motorcycle-related, (1,257-(69.14%)), followed by automobile-related was (301
      (16.56%)) and bicycle injuries (123-(6.8%)). The category of working injury
      comprised by machine crushed cases (332-(45.92%)) followed by cutting (148
      (20.47%)) and impacts (69-(9.5%)). The overall mortality rate in our registry was
      8.3%. ASCOT and TRISS were compared using sensitivity, specificity and
      misclassification rates. Each method had disadvantages in predicting outcomes of
      particular subgroups of patients. ASCOT tends to underestimate the probability of
      survival among patients with head/spinal injuries; while TRISS had a similar
      effect on multiple trauma victims. In conclusion, ASCOT is superior to TRISS in
      correctly predicting severe head trauma cases. However, both methods have their
      limitations in terms of accurate prediction. It is our hope to develop a mixed,
      revised model to better predict patients survival probability. Therefore, it is
      feasible to adopt ASCOT methodology in prediction of trauma patients in Taiwan.
      Expanded database and better methodology need to be developed in further study.

PMID- 9011128
TI  - [119 emergency medical transport of the elderly].
AB  - A retrospective analysis of emergency ambulance transports in the EMS-Tainan was
      made to evaluate the utilization of emergency medical system by the elderly and
      to determine the factors that may influence these transports. The study group
      consisted of 4,090 emergency ambulance transports from 1/1/1195 to 30/4/1995.
      1,017 patients (24%) were aged over 65. The main characteristics of these elderly
      patients were as follows: more non-trauma cases, higher severity of triage, and
      longer total transport time (23.0 +/- 0.5 vs. 18.9 +/- 0.2 minutes) were noted.
      In addition, 136 (13.4%) of the elderly patients were not received by the EMS
      network hospital. The most important factors that affect the total transport time
      in the elderly group were triage classification and trauma, which determined that
      speed of transport. In the elderly group, female patients tend to be older, of
      more severe triage classification, more nontrauma-related, have longer total
      transport time, and have less access to the EMS than male patient. Based on these
      results, we recommended make efficient transport in order to provide better
      emergency care for the elderly. A network linking the elder users with EMS
      dispatch center should improve the efficiency in fulfilling the EMS calls, and
      further investigation about the value of such a network is warranted. It is also
      important to establish a competent and countrywide database for EMS users and to
      pursue ongoing planning in order to evaluate and investigate the needs of EMS for
      elderly patients in the future.

PMID- 9011129
TI  - [Furcation entrance dimension, divergent angle and length of CEJ to furcation
      entrance relate to periodontal therapy].
AB  - In previous studies we have investigated the furcation entrance dimension (FED),
      furcation entrance angle (FEA) and the distance between cementoenamel junction
      and furcation entrance (CEJ-FE) of the first and second molars and compared the
      Chinese with the Caucasians. The aim of the present study was to relate the FED,
      FEA, and distance of CEJ-FE to the clinical significance of periodontal therapy
      of molar furcations. All the FEDs, FEAs, and distance of CEJ-FEs of the molars
      were measured by a stereomicroscope equipped with a Bioscan OPTIMAS Image
      Analyzer and statistically analyzed by Student's paired t-test, multiple
      regression of ANOVA and correlation analysis. The results are summarized below.
      (1) There is a significant relationship between FEA and location of buccal,
      mesial, and distal furcations of maxillary first and second molars (16& 26, p <
      0.001; 17&27, p < 0.01). (2) There exists a significant relationship between FEA
      and FED in the mandibular first and second molars. (3) There exists a significant
      relationship between FED and FEA in the mandibular second molar (r = 0.370, p <
      0.05). (4) The prevalence of mean FED and FEA (type D, FED < or = 0.75 mm and FEA
      < or = 90 degree) of the maxillary first molar (45%) is twice as high as the
      maxillary first molar (24%). (5) The prevalence of type D of the buccal (32%) and
      lingual (37%) furcations on the mandibular second molar is markedly higher than
      the first molar (buccal = 12%; lingual = 4%, respectively). These results reveal
      that those topographics of the FED, FEA, and distance of CEJ-FE in second molars
      have poor prognosis in periodontal therapy when compared with first molars.

PMID- 9011130
TI  - [A cross-sectional radiographic study of proximal alveolar bone loss in molars
      with adult periodontitis].
AB  - The purpose of the present study was to document the mean proximal alveolar bone
      loss of molars. The samples consisted of 219 subjects receiving of full mouth
      radiographs by standardized paralleling technique from Jan, 1992 to Jun, 1994.
      All the radiographs of 219 individuals suffered from adult periodontitis at age
      between 20 and 65 years old were measured, and were assessed mean proximal
      alveolar bone loss of molars and associated contributing factors. The main
      results indicated that (1) the mean proximal alveolar bone loss of the maxillary
      first and second molars accounted for 38. 4% and 33.5%, respectively, whereas the
      mandibular first and second molars were 34.8% and 31.6%, respectively; (2) within
      the same dental arch, mean proximal alveolar bone loss of the first molars was
      significant greater than that of the second molars, while the bone loss in the
      maxillary first molars was significant greater than that of the mandibular first
      molars. There was no difference between mean proximal bone loss of the maxillary
      and mandibular second molars; (3) mean alveolar bone loss of the first molars was
      significant greater than second molars in the same side of the dental arch. There
      was no significant difference in the mean proximal alveolar bone loss between
      right and left side molars. (4) average bone loss was the greatest (39.4%) at the
      mesial surfaces of maxillary first molars, whereas the least mean alveolar bone
      loss appeared at the distal surfaces of mandibular second molars. A significant
      difference of mean proximal alveolar bone loss was found between mesial and
      distal surfaces in mandibular first molars.

PMID- 9011131
TI  - [The shear bond strength of porcelain and base metal alloys for metal-ceramic
      crown the study of metal roughness and microstructure].
AB  - The metal-ceramic crown has become a predominant restoration in fixed
      prosthodontics. The base metal has the quality of lower price, high tensile
      strength, high elastic modulus. The base metal alloy that contain beryllium
      element increases fluidity and improved casting performance. Beryllium also
      controls surface oxidation and affects the metal ceramic bonds. Preparation of
      surface prior to porcelain bonding has been a subject of controversy among dental
      ceramists. Two ceramic base metal alloys (one alloy contains beryllium, another
      is not) were studied. This investigation evaluated the polishing effects of 50
      microns, 100 microns aluminum oxide sandblasting, carbide bur, carborundum point
      and separating disk upon two base metal alloys, Rexillium III and Wiron 88. A
      scanning electron microscope was used to study the surface texture. The following
      results were obtained: 1. The most roughest surface was created with 50 microns
      aluminum oxide sandblasting. The carbide bur produced the least roughed surface.
      2. There are specific surface texture patterns after polishing with five
      different grinding materials. 3. The metal surfaces treated with 50 microns and
      100 microns aluminum oxide have same micro-structure pictures, but there are much
      more undercuts treated with 100 microns aluminum oxide. 4. The usage of carbide
      bur resulted in less undercuts of metal surface at two metal alloys. 5. The usage
      of carborundum point and disk resulted in abrasive particles that retained on the
      grinding metal surface at two metal alloys. 6. The surface of Wiron 88 alloy
      usually had wrinkle texture but not the Rexillium III alloy.

PMID- 9011132
TI  - [Operation directions by comparing financial ratio of 22 provincial hospitals].
AB  - Even more restrictive regulations and reimbursement limits seem to be a very
      heavy burden and stress for most provincial hospitals, especially after the
      National Health Insurance System has been introduced. The purpose of this project
      to find a better, universal direction for these hospitals through three steps: 1)
      Using different financial and accounting ratio indexes to evaluate the general
      business performance of each hospital. 2) Taking a comprehensive questionnaire
      with senior managers of each hospital to know their concepts and attitudes
      concerning external environment and internal operation. 3) Comparing data's
      correlation and differentiation to ascertain better trends for future operation
      for all hospitals. The database for this project comes from two resources: 1)
      Government finance and budget reports of 22 provincial hospitals for the 1994
      accounting calendar year. 2) The results of questionnaires returned by 274 senior
      managers of hospitals, and analysis of these by chi-square test. Through
      statistical comparison, a number of conclusions can be made: 1) Most hospitals
      have better operation efficiency if any professional hospital administrator is
      working for them. 2) The hospital with more comprehensive personnel system shows
      better business performance. 3) The hospital with routine and formal financial
      analysis reports always has better business performance. 4) The hospital with
      poor operational efficiency tends to get rid of restriction or limitation from
      government's system. 5) The hospital with good operational efficiency has more
      confidence and desire to improve and change. 6) The hospital with poor
      operational efficiency is more dependent on outside support from government. 7)
      The hospital with better business performance has more concern about the impact
      of malpractice around the hospital. In short, a hospital with poor business
      efficiency always has more pessimistic attitude and tends to rely on outside
      resource support. On the other hand, a hospital with more confidence, flexibility
      and readiness for internal improvement always demonstrates greater business
      efficiency.

PMID- 9011133
TI  - [Serodiagnosis of tuberculosis by detection of antituberculous glycolipid antigen
      (TBGL antigen) antibodies in serum using enzyme-linked immunosorbent assay:
      clinical evaluation of anti-TBGL antibodies assay kit].
AB  - Kyowa Medex Co., Ltd. developed the kit for the sero-diagnosis of tuberculosis,
      which detects IgG antibodies against tuberculous glycolipids antigen containing
      cord factor (TBGL antigen) prepared from M. tuberculosis using the enzyme-linked
      immunosorbent assay technique. We evaluated the kit using clinical specimens and
      the results are as follows: 1) In total, 34 out of 39 cases (87.2%) with active
      pulmonary tuberculosis showed positive anti-TBGL antibody. 2) Patients with
      cavity, patients with extensive lesions and patients excreting large amount of
      acid fast bacilli tended to show high positivity rates. 3) The antibody titers
      increased in 7 out of 11 cases after starting the antituberculous chemotherapy.
      4) The use of the antibody is unsuitable for the determination of the activity of
      tuberculosis since the antibody titers only slightly decreased even after
      chemotherapy for two years. 5) Two out of four nontuberculous mycobacteriosis
      cases showed high antibody titers 6) All three AIDS patients with tuberculosis
      showed low antibody titers. 7) The antibody was negative in almost all healthy
      controls showing a positive PPD skin test after vaccination with BCG, and it was
      therefore assumed that the antibody titer is not increased by BCG vaccination. 8)
      The antibody titers of the staff members working in the tuberculosis wards were
      not high compared with those of staff members working in the other wards.

PMID- 9011134
TI  - [Differential diagnosis of tuberculous pleurisy by the measurement of cytokine
      concentration in pleural effusion].
AB  - Pleural fluids obtained from 26 patients with tuberculous pleurisy (T-group), 11
      with parapneumonic pleurisy (B-group) and 21 with malignant pleurisy (M-group)
      were tested for their biologic parameters and cytokine concentrations. 1) The
      average age of T-group was over 10 years lower than that of M-group with a
      statistically significant difference. 2) The average CRP value of B-group and the
      positivity on PPD skin test of T-group were higher than those of the other
      groups, respectively. 3) Yellowish pleural fluids were mainly observed in T- and
      B-group, while bloody pleural fluids were mostly seen in M-group with a
      statistically significant difference. The average total protein amount and
      adenosine deaminase value in pleural fluid significantly increased in T-group.
      The percentage of polymorphonuclear leukocytes showed a significant increase in B
      group, while lymphocytes significantly increased in T-group with a statistically
      significant difference. 4) Although no significant difference in concentrations
      of IL-1 beta, IL-2, IFN-gamma and TNF-alpha in serum was noticed among the three
      groups, the average concentrations of IFN-gamma and TNF-alpha in pleural fluid in
      T-group were significantly higher than those in the other groups. 5) TNF-alpha
      mRNA of mononuclear cells in pleural fluid was strongly expressed in 3 out of 11
      patients of T-group, while no expression was observed in 6 patients of M-group.
      In conclusion, the measurement of concentrations of two kinds of cytokines in
      pleural fluid, IFN-gamma and TNF-alpha, may be clinically useful for the
      differential diagnosis of tuberculous pleurisy from parapneumonic pleurisy and
      malignant pleurisy.

PMID- 9011135
TI  - [A case report of tuberculosis epidemic in a university].
AB  - Index case (S.K.) was a postgraduate in one institute of Tohoku University and
      was diagnosed as pulmonary tuberculosis by regular health check-up. Examinations
      of sputa indicated Gaffky 6 on smear and +3 in culture, respectively. Five months
      after the diagnosis of the index case, a professor (O.K.) who was teaching S.K.
      in the same institute was diagnosed as tuberculosis by the chest X-ray survey.
      One month later, another postgraduate (M.J.) studying in other institute was
      found to affected with tuberculosis by regular health check-up. Since two
      institutes were distant from each other, it seemed that neither S.K. nor O.K. had
      an opportunity to contact with M.J. It was revealed, however, that two
      postgraduates received some lecture in the same classroom twice a week.
      Considering all these facts, three cases presented here are regarded as
      tuberculosis outbreak in the university.

PMID- 9011137
TI  - [Enamel maturation and matrix removal: a morphological aspect].

PMID- 9011138
TI  - [Histological observations on structure of bundle bone in area of mylohyoid
      line].
AB  - The purpose of this study was to investigate the structure and the function of
      the part of the mandible where mylohyoid muscle originates. The bundle bone in
      the area of mylohyoid line and the tendon fibers on the surface of the bundle
      bone were observed by light microscopy and scanning and transmission electron
      microscopy. The conclusions were as follows: 1. It seemed that remodeling occurs
      frequently in bundle bone in the area of the mylohyoid line. 2. Sharpey's fibers
      in bundle bone in the area of the mylohyoid line seemed to be flexible. This
      suggested that Sharpey's fibers can be adapted to the tension from directions
      that are different to a certain degree. 3. Both directions of Sharpey's fibers in
      bundle bone in the area of the mylohyoid line and the tendon fibers on the
      surface of bundle bone were fundamentally the same as that of the muscle fibers
      of the mylohyoid muscle. But a few existing fibers crossed these fibers. Such
      Sharpey's fibers and tendon fibers seemed to prevent the exfoliation of the
      periosteum, and seemed to support main tendon fibers of the mylohyoid muscle when
      it is contracting.

PMID- 9011139
TI  - [Study on porcine proteoglycans relevant to structure and function of
      temporomandibular joint].
AB  - The purpose of this study was to characterize the biochemical and immunological
      properties of the temporomandibular joint (TMJ). Proteoglycans (PGs) were
      extracted from the porcine TMJ retrodiscal tissue (RT) and superficial fibrous
      layer of condyle (SLC). The proportion of Glycosaminoglycans (GAGs) with TMJ
      disc. RT and SLC resembled that of disc and RT GAGs, but SLC GAGs were different
      from others. TMJ disc had a higher Dermatan sulfate/Chondroitin sulfate ratio
      than that of RT. and TMJ disc had stronger tensional load resistance than that of
      RT. Immunologically, a high molecular weight PG resembled Aggrecan and two low
      molecular weight PGs resembled Decorin and Biglycan. Total RNA was isolated from
      SLC, and RT-PCR was performed. These products were sequenced, and these sequences
      were compared to the sequences of porcine Aggrecan, human Decorin and Biglycan.
      These results suggested that TMJ had Decorin, Biglycan, and Aggrecan. The
      difference of PG quantity in each region seemed to be associated with the
      pathological conditions found on each component of TMJ.

PMID- 9011140
TI  - [Anterior denture teeth selected for complete dentures].
AB  - The purpose of this study was to investigate the influence of sex and age on the
      selection of color, size, and form of anterior teeth for complete dentures. A
      sample representing one hundred eighty-five edentulous patients whose complete
      dentures were made with. Real Crown teeth (Shofu Inc.) was obtained. The results
      were as follows: 1) Lighter teeth were selected for females than males, but age
      had no relation to the selected color of the teeth. 2) Larger teeth were selected
      for males than females, but age had no relation to the selected size of the
      teeth. 3) The combination and tapering forms were selected frequently, the
      combination form was used more frequently for females than males and the tapering
      form was used more frequently for males than females.

PMID- 9011141
TI  - [A clinical and physiological evaluation of masticatory center in shortened
      arch].
AB  - The aim of this study was to evaluate the influence of occlusal deficit by loss
      of bilateral posterior molars in masticatory habituation and how to improve by
      RPD, investigating the location center of occlusal load (by Prescale Fuji Film
      Co.) and in its amount, in connection with masticatory muscle activities by
      analyzing EMG. EMG measurements of masticatory masculature at maximal clenching
      with pressure indicator, were induced at intercuspal position, confirming by MKG.
      As controls, seven complete dentate adults were referred, the five mandibular and
      maxillary bilateral molar-edentate cases each of five were investigated. The
      results were as follows: i) The location of the center of the occlusal load in
      dentate mouth was about the midline of the maxillar first molar. ii) In the loss
      of bilateral molars, the center of the occlusal load was in the first premolar
      area. iii) By prosthodontic treatments the center of the occlusal load was
      changed to the second premolar area. iv) These results indicated that the
      prosthodontic treatment was estimated in physiological imperfection of recovery
      as yet dentate mouth.

PMID- 9011142
TI  - [A fundamental study on measurement of study cast].
AB  - The dental study cast has a complicated shape. Therefore, many dead angles are
      recognized during three-dimensional (3-D) measurement using a light source. To
      overcome this problem, several divisional measurement methods have been
      developed. However, in these methods, inadequate accuracy and the discontinuity
      of data were observed on the reconstructed image. In this study, a new divisional
      measurement method was developed and the overall accuracy was evaluated. The
      standardized stone model, which has three spheres, was kept by the specifically
      designed high precision jig. The distances between the reference points of each
      sphere were measured by using a 3-D curved shape measurement apparatus with a
      laser source. Then the values were compared with those obtained by using a
      contact type 3-D measurement apparatus. There were slight differences between the
      two methods, but they were not statistically significant. In addition, when the
      individual data were combined, the distances between the reference points of each
      sphere were not significantly different. These results suggested that the shape
      of the study cast can be accurately measured by the divisional measurement
      method.

PMID- 9011143
TI  - Controversies about amyotrophic lateral sclerosis.
AB  - Controversy regarding amyotrophic lateral sclerosis (ALS) concerns aspects of
      relatively little consequence (such as the role of lead intoxication or trauma in
      the pathogenesis of the disease) and others of greater relevance, particularly
      the two following questions regarding treatment options: 1) Are we in a new era
      of therapy for ALS? Prior to the 1990's no controlled study showed consistent
      benefit from any of the treatments tried. We have now had announcements of
      benefit for four entirely different agents: riluzole, insulin-like growth
      hormone, brain derived neurotrophic hormone and gabapentin. The benefit, at most,
      is marginal or questionable. The effect is of statistical significance but of
      little clinical relevance, and 2) what is the role of peripheral nerves in ALS?
      The syndrome of multifocal motor neuropathy and conduction block (MMNCB) shares
      some clinical data (active tendon jerks in weak, wasted and fasciculating
      muscles) and pathological features (anterior horn cell loss and glions) with
      "typical" ALS. This is relevant because MMNCB is reversible with immunoglobulin
      therapy. The rigid separation between ALS (a disease of the motor neuron
      perikaryon) and MMNCB (a disease of the motor neuron axon) is no longer tenable.

PMID- 9011144
TI  - [The ethanol elimination pharmacokinetics--the effects of genotypes of ALDH2 and
      CYP2E1 on the ethanol metabolism].
AB  - The effects of the genotypes of CYP2E1, ALDH2, ADH upon the blood ethanol and
      acetaldehyde levels were investigated. The predicting 95% confidence bounds
      determined on regression analysis of the data suggested that after venous
      injection of ethanol, the blood ethanol and acetaldehyde concentrations in a
      volunteer normal homozygous for ALDH2 (ALDH2*1/1) were significantly lower than
      that heterozygous (ALDH2*1/2). And the blood ethanol and acetaldehyde
      concentrations in a volunteer with C2 allele (C1/C2) were significantly lower
      than that in (C1/1). However, there were no significant differences in the blood
      ethanol and acetaldehyde concentrations between volunteers with ADH2*1/1 and
      ALDH2*1/2. It is possible that the ALDH2*1 and C2 alleles may correspond to the
      lower blood ethanol and acetaldehyde concentrations after intravenous
      administrations of 0.2 g /kg of ethanol.

PMID- 9011145
TI  - [ERP study of information processing disturbance on schizophrenia--from aspects
      of automatic processing and controlled processing].
AB  - We studied the relationship between automatic processing and controlled
      processing in schizophrenic disorder and examined the changes of the relationship
      through various clinical courses of the illness using event related potentials
      (ERPs). Thirty schizophrenic patients were classified into two groups according
      to ERP variations; group-A consisted of schizophrenics who showed higher mismatch
      negativity (MMN) amplitudes and lower P300 amplitudes than group-B patients.
      After pharmacological treatment, MMN amplitudes decreased and P300 increased in
      group-A patients. On the other hand, MMN amplitudes increased, but no significant
      changes in P300 amplitudes were recognized in group-B patients. MMN amplitudes
      had a negative correlation with the extent of dilatation of the left Sylvian
      fissure and the bilateral lateral ventricles on CT scans. From these results, it
      is suggested that automatic processing and controlled processing complement each
      other in information processing of schizophrenics. In group-A, higher MMN
      amplitudes suggested plasticity of processing dysfunction, which showed good
      social adjustment after pharmacological treatment. In group-B, more severe
      vulnerability to the disorder was suggested from lower MMN amplitudes, which
      showed poor social adjustment after the treatment.

PMID- 9011146
TI  - [The efficacy of short-term hospitalizations in family care for patients with
      Pick's disease].
AB  - The purpose of this study is to investigate the efficacy of short-term
      hospitalization on family care for patients with Pick's disease (PD). Subjects
      were 12 patients with clinical diagnosis of PD based on clinical and neuroimaging
      criteria. They were selected from 483 patients with cognitive disorders who had
      been admitted to our hospital from January, 1994 to September, 1995. During 1.5
      month hospital stay, we gave therapeutic intervention to the patients and their
      care-givers. Ten patients completed the planned term (1.5 months) of
      hospitalization. After the discharge, 9 patients continued to visit regularly the
      outpatient clinic. One patient discontinued to visit us and 2 patients were
      admitted to psychiatric hospitals because of stereotypic thefts or
      disinhibitional behavior. The benefits of short-term hospitalization in family
      care for PD patients were; i) close observation and analysis of patients'
      behavior under hospitalization offering strategies of behavioral therapy; ii)
      adequate instruction to the care-givers for their preparation for patients'
      malbehavior decreasing their burden; and iii) patients' familiarization to the
      hospital helping for patients to maintain regular visit to the hospital and to
      utilize other medical and social resources.

PMID- 9011147
TI  - New aspects of ketone bodies in energy metabolism of dairy cows: a review.
AB  - Increased lipolysis, low insulin/glucagon ratios and malonyl-CoA concentrations
      are prerequisites for ketogenesis. From an aetiological viewpoint, there are two
      quite different types of metabolic disorders in which ketosis can occur, the
      hypoglycaemic-hypoinsulinaemic and the hyperglycaemic-hyperinsulinaemic type. The
      former, Type I, generally occurs 3-6 weeks after calving in cows whose milk
      secretion is so extensive that the demand for glucose exceeds the capacity for
      glucose production. To protect the body from hazardous protein degradation by a
      high rate of gluconeogenesis, this process is inhibited and the increased energy
      requirements are met by the elevated utilization of ketone bodies. In this strong
      catabolic metabolic state the plasma levels of glucose and insulin are very low,
      the levels of ketone bodies are high and there are small risks for fat
      accumulation in the liver cells. The hyperglycaemic, hyperinsulinaemic form, Type
      II, generally occurs earlier in lactation. An important aetiologic factor is
      overfeeding in the dry period, which can lead to disturbances in the hormonal
      adaptation of metabolism at calving with increased plasma levels of insulin and
      glucose and often out not always also with hyperketonaemia. If combined with
      stress, there may be increased lipolysis in adipose tissues, lipid synthesis and
      accumulation in the liver, i.e. the development of fatty liver. This
      hyperglycaemic form of disturbance has many similarities with the initial stage
      of non-insulin-dependent (Type II) diabetes in humans. It has been shown that
      ketone bodies inhibit protein degradation and thereby gluconeogenesis and also
      are able to spare glucose by inhibiting glucose utilization. They also can
      inhibit lipolysis and function as a regulatory safety system, replacing insulin,
      in situations when the activity of this hormone is low, as in Type I ketosis.
      Ketone bodies thus have important functions as substrates replacing glucose in
      many tissues and also as signal substances in the regulation of energy
      metabolism.

PMID- 9011148
TI  - Formation and persistence of N7- and O6-methyl-guanine in DNA of chick embryo
      brain cells in ovo following administration of N-nitroso-N-methylurea.
AB  - Previously, O6-methyl-guanine-DNA alkyltransferase (AT) of the chicken embryo has
      been investigated in vitro. In the present studies, the effect of in vivo (in
      ovo) treatment with methylnitrosourea (MNU) was examined at a developmental stage
      of 15 days and doses of 1.25-20 mg/egg, yielding about 1-16 mmol MNU/kg embryo
      weight. At intervals of 1-24 h, DNA of the brain was prepared. N7-methylguanine
      and O6-methylguanine were quantified by combining a rapid method of DNA
      isolation, high-pressure-liquid-chromatography (HPLC) and electrochemical
      detection of the guanine-alkyl adducts. In parallel, the AT activity of brain
      homogenates was determined. Within the range of the detection limits (N7
      methylguanine: 16 nM, O6-methylguanine: 2.5 nM), no repair of the guanine
      adducts, being about 500 nmol O6-methyl- and 1800 nmol N7-methyl-adducts per mmol
      guanine 1 h following administration of 10 mg MNU/egg, was evident. The rather
      low acute toxicity of MNU in the chicken embryo at the 15th day of development
      DL50/24 h being > 4 mg MNU/embryo, argues, therefore, for an additional repair
      mechanism, e.g. cell replacement repair.

PMID- 9011149
TI  - Effect of cholera toxin on glucose absorption and net movements of water and
      electrolytes in the intestinal loop of sheep.
AB  - This study was designed to evaluate the effect of cholera toxin on glucose
      absorption and net movement of water and electrolytes in the jejunal loop of
      sheep. Intraluminal perfusion was performed at the rate of 1 ml/min with isotonic
      10 mM glucose solution. Osmolality was adjusted by adding NaCl, and the outflow
      solution was collected every 10 min. After a 30 min control period, cholera toxin
      was applied intraluminally for 30 min at doses of 30, 60, and 120
      micrograms/loop. In the control period, water, sodium and chloride were absorbed,
      while potassium and bicarbonate were secreted. Cholera toxin reversed the net
      absorption of water, sodium and chloride to net secretions, and this secretory
      response to cholera toxin was dose-dependent. Bicarbonate secretion was
      stimulated dose-dependently by cholera toxin. Potassium secretion was also
      increased at all doses, though this response was not dose-dependent. The net
      glucose absorption was decreased dose-dependently by cholera toxin. In
      conclusion, these results indicate that cholera toxin stimulates water and
      electrolyte secretion, and inhibits glucose absorption in the jejunal loop of
      sheep.

PMID- 9011150
TI  - Mitotic phase distribution, mitotic activity and apoptosis in basal cell tumours
      of canine skin.
AB  - This study evaluates the mitotic phase distribution, mitotic activity and
      apoptosis in 17 basal cell tumours of canine skin. The number of mitotic and
      apoptotic cell/mm2 of neoplastic epithelium is counted and the volume corrected
      mitotic and apoptotic index, respectively, are obtained (M/V and A/V index).
      Transmission electron microscopy is performed on selected cases to confirm the
      typical features of apoptosis. The M/V index ranges from 9 to 45/mm2 of
      neoplastic epithelium, while the A/V index ranges from 5 to 111/mm2 of neoplastic
      epithelium. Even if the number of apoptotic cells is slightly higher than that of
      mitotic cells and vice versa, the mean values of the two parameters (mean M/ V =
      20.76 +/- 10.86, mean A/V = 31.41 +/- 24.53) tend to be equal. In fact, apoptotic
      and mitotic index are not statistically different (P = 0.11). Furthermore, in all
      the samples examined, an increased proportion of metaphases (46.82%) is observed.
      These findings suggest that the discrepancy between apparent mitotic activity and
      tumour growth may be mainly due to the increased duration of the entire cell
      cycle rather than to the high incidence of apoptosis.

PMID- 9011151
TI  - Morphological studies on experimental oleander poisoning in cattle.
AB  - Oleander poisoning has been reported in man and animals. The present experiments
      address the gross and microscopic changes due to oleander poisoning in cattle.
      Minimum lethal doses (50 mg/kg) of oleander leaves were orally administered to
      three calves in a single dose each of the other three animals received the same
      lethal dose in three equal parts with 24-h intervals. The lesions in the three
      animals which received 50 mg/kg in a single dose resulted from the direct effect
      of the toxin on the vascular endothelial bed and demonstrated as petechial and
      diffused haemorrhages, congestion, oedema, cell degeneration and inflammatory
      cell infiltration in the lungs, heart, mesentry, kidneys, serosal and mucosal
      surfaces of omasum, abomasum and the intestine. The lungs also showed
      atelectasis, emphysema and disseminated intravascular coagulation. On the other
      hand, the animals which received divided doses showed lesions due to long-term
      exposure to the toxic agent and/or as the result of tissue ischaemia. The lungs
      also showed cell necrosis and mononuclear cell infiltration in the interstitial
      tissue, and some of the cardiac muscle fibres rather showed fibromyolysis and
      cell infiltration between muscle fibres, epicardium and endocardium. The
      intestinal villi showed haemorrhagic, degenerative and necrotic changes and the
      eosinophils were infiltrated in mucosal and submucosal layers of this organ.
      Multifocal degenerative and necrotic changes with inflammatory cell infiltration
      were also present in the liver parenchyma.

PMID- 9011152
TI  - Cardio-respiratory and plasma lactate responses to exercise with low draught
      resistances in standardbred trotters.
AB  - Five Standardbred trotters performed treadmill exercise with incrementally
      increasing trotting velocities for 2 min intervals in three different tests until
      fatigue. Each test was performed with draught loads of either 10, 20 or 30
      kilopond (kp). Each trotting interval was followed by 2 min periods at a walk
      without draught load. Recordings were made of heart rate (HR), respiratory rate
      (RR), plasma lactate (PLA) and stride frequency (SF) at the end of each trotting
      interval. The HR increased to average values of 191 +/- 10,203 +/- 10 and 214 +/-
      7 bpm and PLA increased to 3.8 +/- 0.7, 7.3 +/- 3.8 and 10.8 +/- 6.4 mmol/l at 9
      m/s in the three tests, respectively. The HR response to exercise was
      significantly higher with increasing draught loads, and PLA was significantly
      higher with 30 kp compared to 10 kp draught resistance. The lowest respiratory
      rate was seen in the test with 30 kp loading. Peak oxygen uptake (VO2peak) was
      measured in a separate test on a sloped treadmill with increasing velocities
      without draught load and averaged 70.4 +/- 9.11/min. Muscle biopsies were taken
      from the gluteus muscle. Individual variations were seen in VO2peak, muscle fibre
      composition and HR and PLA responses to exercise. In conclusion, at a certain
      velocity a small increase in draught resistance from 10 to 30 kp significantly
      increases both the HR and PLA responses. At comparable work intensities the
      horses differed in circulatory and metabolic responses to exercise.

PMID- 9011153
TI  - Detection of Vibrio anguillarum by a sandwich enzyme-linked immunosorbent assay
      performed with monoclonal antibodies.
AB  - Monoclonal antibodies (Mabs) against V. anguillarum were produced and
      characterized by Western blotting analysis, competitive binding assays and cross
      reactivity tests. Their ability to detect V. anguillarum in a liquid culture was
      tested in a sandwich enzyme-linked immunosorbent assay (ELISA) performed with
      different combinations of these Mabs used as capture or tracer antibodies. One
      combination was selected as the most suitable for diagnostic applications,
      showing the highest sensitivity and specificity.

PMID- 9011154
TI  - Differentiation of Pasteurella multocida subspecies multocida isolates from the
      respiratory system of pigs by using polymerase chain reaction fingerprinting
      technique.
AB  - PCR fingerprinting technique was applied to subtype 44 Pasteurella multocida
      subspecies multocida (P.m.sp.m.) isolates from the respiratory system of pigs.
      Two single primers were tested for their abilities to generate individual
      fingerprints by using PCR. Primer 1 (core sequence of the M13 phage) grouped the
      44 P.m.sp.m. strains into five distinct fingerprinting profiles, while primer 2
      ((GACA)4) grouped them into seven profiles. The results suggest that PCR
      fingerprinting is an efficient technique to detect DNA polymorphism in the
      species P.m.sp.m. This technique could be used to differentiate P.m.sp.m. strains
      of the same capsular serotype.

PMID- 9011155
TI  - Environment, incidence, aetiology, epizootiology and immunoprophylaxis of soil
      borne diseases in north-east Mexico.
AB  - Within the framework of an extensive research programme, the socio-economic and
      environmental conditions which influence the emergence of soil-borne diseases in
      north-eastern Mexico were analysed. Furthermore, specimens collected from
      carcasses in the field were bacteriologically examined and the causal organisms
      of soil-borne diseases differentiated by means of gas chromatographic analysis of
      their metabolic products and the long-chained fatty acids contained in the cell.
      With experimental clostridial vaccines prepared with the Goettingen Bioreactor
      Technique, trials to protect cattle and guinea-pigs against gas gangrene were
      carried out. It was found that the farm structure and the dry climate as well as
      the specific soil conditions and plant cover favour the emergence of soil-borne
      diseases. Causal organisms B. anthracis, C. perfringens, C. sordellii, C.
      haemolyticum, C. chauvoei/septicum, C. novyi A, C. botulinum and site-specific
      field strains of clostridia were detected. Experimental site-specific vaccines
      proved to be highly efficient in protecting cattle and guinea pigs.

PMID- 9011156
TI  - Immunoreactive cytokines within primates.
AB  - Peripheral blood mononuclear cells of primates (man, orang utan, gorilla,
      baboon), rodents (mouse, rat), carnivores (cat, dog), artiodactyls (cattle, goat,
      pig) and perissodactyls (horse) were isolated and stimulated with mitogens (5
      micrograms/ml LPS, 5 micrograms/ml PHA) at 37 degrees C. Cytokines immunoreactive
      to monoclonal antibodies (mAb) directed to human cytokines (TNF-alpha, IL-1
      alpha, IL-2, IL-6, IFN-gamma) could be detected by enzyme-linked immunosorbent
      assay (ELISA) in the case of primates only. The mAb used did not recognize
      cytokines of the other mammalian species investigated. The results demonstrate
      the close relationship within the primates from the immunophysiological point of
      view.

PMID- 9011157
TI  - Immunohistological study of IgA, IgG and IgM in endoscopic biopsies of dogs with
      plasmacytic-lymphocytic colitis.
AB  - The results of a histological and immunohistochemical study of endoscopic colon
      biopsies of dogs with plasmacytic-lymphocytic colitis are reported. The
      histological study revealed that a characteristic infiltrate rich in lymphocytes
      and plasma cells was seen within the lamina propria in all the biopsies. The
      immunohistochemical investigation suggests that IgG is the major antibody in the
      immune response of dogs with plasmacytic-lymphocytic colitis.

PMID- 9011158
TI  - Evaluation of polymerase chain reaction (PCR) application in diagnosis of bovine
      leukaemia virus (BLV) infection in naturally infected cattle.
AB  - The practical application of polymerase chain reaction (PCR) for the diagnosis of
      bovine leukaemia virus (BLV) infections in naturally infected cattle was
      evaluated. Compared to serological tests the PCR was definitely found to be a
      more sensitive method, yielding the highest number of positive results (10% more
      compared to enzyme-linked immunosorbent assay, (ELISA), and 17.7% more compared
      to agar-gel immunodiffusion, (AGID)). In testing cattle from herds with BLV
      incidence under 5%, out of 52 provirus positive cattle only 43 were correctly
      identified by ELISA. When compared to AGID only 37 of the 52 PCR positive animals
      were correctly identified. Of 18 cattle imported from the Slovak Republic and
      kept in a quarantine stable, four were found to be BLV provirus positive by PCR,
      while serological tests indicated one animal positive and three negative.
      Therefore, it is impossible to prevent the spread of the infection from one
      country to another by serological testing only. Moreover, it is feasible to
      identify animals with changing antibody titres correctly by PCR. Using PCR we
      were also able to distinguish BLV infected from uninfected calves that were
      serologically positive due to colostral antibodies. Higher sensitivity of BLV
      provirus detection by PCR was achieved using env gene rather than tax gene
      specific primers. Negative results by PCR in cases of positive serological
      reactions are still possible, as shown in case of one adult animal. These
      findings indicate that PCR is a highly sensitive method and might be successfully
      used and economically advantageous for different practical applications in
      detection of BLV infection in naturally infected cattle.

PMID- 9011159
TI  - An outbreak of Pacheco's parrot disease in psittacine birds recently imported to
      Campania, Italy: isolation of psittacid herpesvirus 2.
AB  - The authors describe an outbreak of Pacheco's Parrot Disease (PPD) which occurred
      in Italy in recently imported psittacine birds and was caused by Psittacid
      Herpesvirus type 2 (PsiHV2). The authors stress the different susceptibility to
      the disease in the species involved. This outbreak showed the failure of the
      vaccine prophylaxis that had been administered to the birds with ordinary
      commercial preparations containing Psittacid Herpesvirus type 1. The authors
      emphasize the necessity of producing a vaccine containing inactivated viruses of
      all known serotypes.

PMID- 9011160
TI  - Direct detection of equine herpesvirus DNA in tissues of aborted equine fetuses.
AB  - Restriction endonuclease analysis of equine herpesviruses 1 (EHV-1) and 4 has
      been investigated using cultured cells infected with these viruses. The DNA
      cleavage patterns of these viruses were observed in the intracellular DNA after
      digestion with Eco RI and electrophoresis. This procedure was applied to the
      diagnosis of equine herpesvirus infection in aborted equine fetuses. The
      characteristic Eco RI restriction pattern of EHV-1 DNA was directly detectable in
      the emulsion of lungs collected from aborted equine fetuses.

PMID- 9011161
TI  - The organization of the Child Neurology Society: a personal view.

PMID- 9011162
TI  - [Physician-patient relations: alliance... collaboration or... commercial
      transaction?].

PMID- 9011163
TI  - [Cognitive reconceptualization in the perception of sex activity in the aged:
      structural neoformation of attitudes to sexuality in old age].

PMID- 9011164
TI  - [Complementarity in medical practice].

PMID- 9011165
TI  - [Importance of plasma (histamine and tryptase) and urinary (methylhistamine) in
      peri-anesthetic anaphylactic and/or anaphylactoid reactions].
AB  - Histamine and tryptase, released during anaphylactoid reactions in anaesthesia,
      can be measured out by radioimmunoassay, provided that their own pharmacokinetic
      is respected. For two years, we have used sample kits in order to realize the
      measuring out of these mediators. The aim of this study was to evaluate the
      interest of these mediators within investigational procedures for anaphylactoid
      reactions. Eleven anaphylactoid reactions were observed (0,03%). The early blood
      samples (the first ten minutes following onset of the reaction) were made only in
      36% of the cases. Within the serious reactions (grade III), the raising of
      tryptase indicates the involvement of mast-cell activation. Within minor clinical
      reactions (grade I), plasma histamine and urinary methylhistamine were the only
      mediators detected. In an anaphylactic reaction of grade II, which happened after
      the administering of vecuronium, tryptase was not detected. Therefore, these
      mediators give the anaesthetists the possibility to prove quickly the severity of
      the reactions and to direct the investigations very early towards the right way.

PMID- 9011166
TI  - [Ebastine : treatment of perennial rhinitis in the child].
AB  - Ebastine is H1 receptor antagonist, powerful and selective for histamine. Its
      efficacy has been evaluated in control of symptoms of persistent rhinitis,
      appearance of secondary effects and tolerance of the drug, in 30 children who
      were suffering from persistent rhinitis, of which the diagnosis included:-
      clinical history, skin tests (prick test) nasal and conjunctival provocation
      tests, total and specific IgE. All the children had treatment for 30 days. The
      parameters followed were:- clinical score, skin tests, nasal and conjunctival
      provocations and evaluation of secondary effects, of the start and 10 days after
      the end of treatment. The results obtained were a disappearance or reduction of
      the weals from histamine and specific antigens, disappearance or reduction of the
      response in nasal and conjunctival provocation with carbachol or specific
      antigens, clear clinical improvement in 22 patients, in 2 small improvement and
      no response in 6 patients. We conclude that Ebastine improved the clinical
      symptoms in persistent rhinitis, the skin test is inhibited and sensitivity of
      the shock organ is reduced. No secondary effects were seen on the Central Nervous
      System (SNC) and the tolerance of the drug was very good.

PMID- 9011167
TI  - [Portable emergency kits prescribed for patients allergic to hymenoptera venoms].
AB  - Allergy to hymenoptera venoms may produce anaphylactic reactions that are severe
      in 0.8 - 5% of the adult population, according to different epidemiological
      studies. The risk of a severe reaction in allergic patients who have not been
      desensitized is 50%. This risk falls to 5 - 10% for allergy to wasp and to 10 -
      20% for allergy to bee (1, 2, 3, 4). Because of this serious and vital risk,
      there is a consensus to prescribe an emergency kit that contains auto-injectable
      adrenaline (5). An enquiry was made of the allergists of ANAFORCAL and their
      patients to find the actual practice in comparison with this consensus... 80
      physicians and 181 patients replied. It seems that adrenalin is almost always
      prescribed, together with other products (antihistamines and corticosteroids the
      most frequent). On the other hand, the following of prescriptions by the patient
      is not always perfect. It is important therefore to check that the kit is
      regularly carried, that it is still valid and to be sure that the patient always
      knows how to manage the product.

PMID- 9011168
TI  - [Questions about transgenic foods--importance and/or dangers-- importance of
      research on unexpected cross-reactions].

PMID- 9011169
TI  - [Unusual clinical form of amoxicillin allergy].

PMID- 9011171
TI  - [Guidelines for the prevention of opportunistic infections in persons with HIV or
      AIDS in Latin America and the Caribbean. USPHS/IDSA].

PMID- 9011170
TI  - [Histamine liberation (or histamine release HR): study of the positivity
      threshold in hymenoptera venom allergy].
AB  - Dialysis of Hymenoptera venoms for measurement of HR by the radioimmunoassay
      technique (RIA, Immunotech) lowers the threshold of positivity of the HR titre
      from 30% to 12%. This modification of dialysis of the venoms significantly
      improves the sensitivity and specificity of the technique.

PMID- 9011173
TI  - Rethinking women's health: implications for research, medical care, and public
      policy.

PMID- 9011172
TI  - [Specialized care of neurological diseases in Colombia].
AB  - This study sought to reveal the patterns of medical care given to patients with
      neurologic diseases in Colombia. To that end, it tracked the daily activities of
      30 neurologists chosen from a representative sample of 119 neurologists
      registered in Colombia in 1993. The information was requested by means of a
      previously standardized questionnaire and was complemented by demographic and
      epidemiologic data. The results showed that demand for specialized neurologic
      care depended more on cultural perceptions than on objective measures of
      prevalence. Moreover, it was found that education in neurology should place
      greater emphasis on ambulatory treatment as an alternative to hospital treatment.
      The survey also offered preliminary information on the prevalence and incidence
      of the primary neurologic diseases in the country. The prevalence of these
      diseases far exceeds the supply of specialized neurologic care. Finally, the
      results point out the advantages and deficiencies of this type of care, findings
      that might guide future efforts in this field in other countries and under
      different circumstances.

PMID- 9011174
TI  - The X-Factors.

PMID- 9011175
TI  - Transcription factors coupled to the cAMP-signalling pathway.

PMID- 9011176
TI  - The Myb oncoprotein: regulating a regulator.

PMID- 9011177
TI  - Genetic epidemiology of childhood cancer.

PMID- 9011178
TI  - The PML nuclear compartment and cancer.

PMID- 9011179
TI  - Cancer gets Mad: DPC4 and other TGFbeta pathway genes in human cancer.

PMID- 9011180
TI  - Avian erythropoiesis and erythroleukemia: towards understanding the role of the
      biomolecules involved.

PMID- 9011181
TI  - Transcriptional enhancement by acidic activators.

PMID- 9011182
TI  - p53: upstream, downstream and off stream. Review of the 8th p53 workshop (Dundee,
      July 5-9, 1996).

PMID- 9011183
TI  - [Plasmid DNA strand breaks induced by laser irradiation of 193 nm wavelength].
AB  - DNA of plasmid pBR322 irradiated with laser at a wavelength of 193 mm was treated
      with an extract containing proteins from E.coli K12 AB1157 (wild-type). The
      enzymes were found to produce single- and double-strand DNA breaks, which was
      interpreted as a transformation of a portion of cyclobutane pyrimidine dimers and
      (6-4) photoproducts into nonrepairable single-strand DNA breaks. The products
      resulted from ionization of DNA, in particular, single-strand breaks, transform
      to double-strand breaks. A comparison of these data with the data on survival of
      plasmid upon transformation of E.coli K12 AB1157 enables one to assess the
      biological significance of single- and double-strand breaks. The inactivation of
      the plasmid (in AB1157) is mainly determined by the number of directly formed
      laser-induced single-strand breaks, whereas the contribution of enzymatically
      produced single- and double-strand breaks is insignificant.

PMID- 9011184
TI  - [Analysis of ribonuclease and lysozyme interactions with liposomes using
      fluorescent probes].
AB  - Using fluorescent probe 4-(dimethylaminostyryl)-1-methylpridine n
      toluenesulfonate (DSM) the effect of ribonuslease and lysozyme on the structure
      of liposomes composed of phosphatidylcholine and diphosphatidylglycerol has been
      studied. An analysis of DSM spectra contour has been carried out and parameters
      of inhomogeneous broadening has been estimated. Polarity of the probe
      surroundings was found to decrease upon lipid-protein complexes formation.

PMID- 9011185
TI  - [Circular dichroism spectral characteristics of liquid-CRYSTAL     dispersions of
      double-stranded DNA and DNA complexes with dyes].
AB  - The circular dichroism spectra of liquid-crystalline dispersions formed of double
      stranded DNA molecules were calculated. It was found that the amplitude and sing
      of the anomalous band in these spectra in the region of absorption of nitrous
      bases depend on the size of dispersed particles, the pitch of their cholesterol
      helix and the sign of its spatial winding. The theoretical calculations are
      compared with experimental data characterizing the anomalous optical properties
      of liquid-crystalline DNA dispersions and synthetic polynucleotides formed as a
      result of phase elimination in aqueous salt solutions of polyethyleneglycol. The
      theoretically calculated circular dichroism spectra of liquid-crystalline DNA
      dispersions agree with the circular dichroism spectra of these dispersions
      observed experimentally.

PMID- 9011186
TI  - [Method for determining concentration of fluorescent probes binding to biological
      structures].
AB  - Fluorescent probes are used to study the structure and functions of proteins,
      biological membranes, lipoproteins, nucleic acids, nucleoproteins etc. The
      binding centers of these biological objects that interact with probes are usually
      rather heterogeneous. It is often impossible to describe the interaction of the
      probe with these centers in terms of simple Langmuir isotherms. Moreover, these
      centers can affect each other; as they are occupied with probe molecules, the
      properties of both free and probe-occupied centers change. The fluorescence
      quantum yield of the probe in different centers is not the same and can change
      due to their reciprocal influences. As a result, It is often impossible to
      determine even the number of probe molecules bound to these centers. In this
      paper we describe a method for determining the number of probe molecules bound to
      a biological object without regard to object heterogeneity and mutual influence
      of the centers. We abandoned the earlier accepted practice of calculating the
      number of bound molecules of the probe from the intensity of its fluorescence.
      Instead, the fluorescence of the probe is used only to compare solutions with
      different concentrations of probes and centers to achieve an equal occupancy of
      the centers with probe molecules. This makes it possible to measure the amount of
      the bound probe irrespective of the heterogeneity of the binding centers even in
      the presence of mutual influence of the centers.

PMID- 9011187
TI  - [Photoreceptor membrane assymetric structure in separated phase state].
AB  - The structure of unbleached bovine retinal rod photoreceptor membranes isolated
      in ficoli density gradient has been studied by means of small-angle X-ray
      diffraction methods. Samples were prepared in the form of thin multilamellar
      films of photoreceptor membranes in phase-separated state induced by partial
      dehydration. Diffraction data were collected using diffractometer with linear
      position-sensitive detector. Phase signs of structure amplitude were determined
      by method [7] and membrane lamellar electron density distribution was calculated
      at 1, 7 nm resolution. The results obtained showed photoreceptor membranes
      isolated in ficoli density gradient to have asymmetric structure which differed
      from that of photoreceptor membranes isolated in sucrose density gradient [1].
      The asymmetry observed may be accounted for different content of lipid L alpha
      and L beta phases in cytoplasmic and intradisk membrane layers. It may be assumed
      that ficoli helps to support membrane native structure.

PMID- 9011188
TI  - [Electron spin resonance determination of copper binding site on  Escherichia
      coli cell membrane].
AB  - The electron-spin relaxation of Escherichia coli cytoplasmic membrane strong
      binding Cu-centers was investigated by means of the microwave power saturation of
      the electronic spin resonance signal. It has been established, that copper
      centres in the strong binding sites of the cytoplasmic membrane E.coli may be
      represented in the following way: 1) isolate copper complexes with small speed of
      the spin-lattice relaxation; 2) isolate copper complexes with increased speed of
      spin-lattice relaxation by means of interaction with rapidly relaxation centres;
      3) dipol-binding clasters; 4) ESR-nondetectable at T = 40 K, exchange-binding
      clasters, which cause increasing of the spin-lattice relaxation speed for isolate
      copper complexes.

PMID- 9011189
TI  - [The change of erythrocyte hydration environment under hormonal stimulation].
AB  - In this work were studied the change of human erythrocytes cell structure
      hydration by modelling the different way of transmembrane signal transformation
      in the cell by super high frequency dielectrometry method in water dispersion
      region. In nondestructive conditions were demonstrated the participate of
      cytoscelet in hormonal stimulation of cells by various molecular mechanisms. The
      change of hydration environment of cell by catecholamines binding were direct
      correlated with hydration parameters agonists and topograph models alpha- and
      beta-receptor complexes.

PMID- 9011191
TI  - [Changes in erythrocyte electrophoretic mobility in patients with neoplasms].
AB  - The connection of electrophoretic mobility of erythrocytes with seria of blood
      clinico-biochemical parameters measured in health men and stomach cancer patients
      was studied. One stomach cancer the increase of electrophoretic mobility of blood
      erythrocytes with modification of distribution curve shape of this index was
      settled. The stirring up of peroxidation lipid processes in erythrocyte
      membranes, the change of membrane permeance for cathions and the action of
      adaptation mechanisms of system plan was shown to be connected to the exposed
      progresses.

PMID- 9011192
TI  - [Mathematical model of neural networks with memory of time interval].

PMID- 9011190
TI  - [Changes in membrane potential and cell volume of Balb C mice T  lymphocytes in
      different physiological conditions in media with different content of D2O].
AB  - It is shown that the changes in membrane potential of thymocytes in aqueous
      medium with a definite D2O concentration are due to changes in the Na/K-ATPase
      activity. Low D2O concentrations activate whereas high concentrations inhibit the
      enzymatic reaction. The experimental data obtained suggest the discreteness of
      functionally active conformations of the enzyme.

PMID- 9011194
TI  - [False irradiation method in magnetobiological experiments with Helmholtz's
      rings].
AB  - To carry on correct investigation of variable magnetic field influence on
      biological objects the method of complex usage of Helmholtz's rings is suggested.
      For this purpose the same Helmholtz's rings are suggested to be used to produce
      false radiation in the control experiments with opposite in phase current in the
      coils of the Rings. Calculations of the homogenuity of the magnetic field are
      made with nomograms drawn. With the aid of the nomograms one can choose
      parameters of the rings, which ensure any presettled degree of screening of
      initial operational magnetic field.

PMID- 9011193
TI  - [31P NMR in vivo study of a rat brain with phosphate metabolism disorders after
      bilateral focal compression ischemia].
AB  - The dynamics of rat brain energy phosphates and intracellular pH was studied
      during the 1st hour after bilateral focal compression ischemia. The increased
      inorganic phosphate signal intensity was observed simultaneously with the
      unchanged pH and phosphocreatine level. Brain energy status was evaluated by the
      ATP level and by the Z-index (the averaged coefficients of correlation between
      NMR measured brain phosphates in a given group of animals). Reversible changes of
      both ATP and Z were observed after 16-28 min of recovery (20% of decrease and
      200% of increase, respectively). Contrary to ATP the Z-value showed a significant
      increase in comparison with a corresponding intact value and with control (sham
      operated animals). The Z-index is proposed as a sensitive criteria of brain
      energy status.

PMID- 9011195
TI  - [About the article "Magnetic field induced by electric current across a man's
      arm" by Pel'ts CD, Chingin IuA, Sinel'nikova SE].
AB  - The article authors' theory propose existence of privileged electric current
      paths that are depended from acupuncture points situation. The theory validity
      examination was made. As it has been discovered the given experimental data were
      collected and processed without minding lots of biophysical and physiological
      phenomenons. So they could not provide a basis of the theory evidence.

PMID- 9011196
TI  - [Luminescence of the endogenous blood porphyrins].
AB  - The luminescence band with the maximum at lamda-633-642 nm has been observed in
      studies of the luminescence spectra of fresh human venous blood serum with added
      erythrocytes from the same blood excited by the impulse nitrogen laser at the
      wavelength lamda-337 nm. This band is corresponds to the luminescence of a blood
      porphyrine, namely protoporphyrine IX. Based on the observed data, we conclude
      that the endogenous blood porphyrine bound by protein is one of the primary
      specific photoacceptors for radiation of the helium-argon laser generating at the
      wavelength lamda-633 nm.

PMID- 9011197
TI  - [Bidomain model for estimation of myocardial electric generators and
      extracellular fields].
AB  - A formulation of the bidomain model is presented for analysis of the
      extracellular electric and magnetic fields of the excitable myocardium with the
      use of relationships of the stationary current electrodynamics. Definitions of
      equivalent generator of extracellular field and equivalent medium are given,
      taking into account the macroscopic anisotropy of the tissue. The model described
      serves as a basis for solving theoretical and practical problems of heart state
      estimation from noninvasive measurements of its electric and magnetic fields.

PMID- 9011198
TI  - [Photochemical reactions in bone tissue induced by excimer laser ultraviolet].
AB  - A phenomenological model of an increase in ultraviolet absorption in bone tissue
      induced by ultraviolet radiation of excimer laser has been developed. It is
      assumed that the increase in absorption is related to photochemical reactions in
      collagen. The model accounts for changes in the intensity of laser radiation due
      to its absorption inside the specimen. From the comparison of experimental and
      calculated results the parameters of the photochemical model were estimated. The
      temperature fields in the specimen were calculated with regard to laser-induced
      changes in absorption coefficient. The limits of applicability of the model are
      discussed.

PMID- 9011199
TI  - [The model of age dependent frequency of neoplasms].
AB  - The equation for the increase of tumor frequency with age is deduced from the
      supposition about the errors of DNA replication as the main cause of oncogenic
      mutations. The quantitative expression of the organ specificity of tumor
      frequency is concluded also. The age function coincide qualitative with
      epidemiologic date: the tumor frequency is in proportion to age with the
      exponents of 5 and higher. The frequency of oncogenic mutations on one DNA
      replication is evaluated from the equation using the statistical data of the
      annual sickness rate of the lip, oral cavity and throat cancer for the men and
      the rate of cell proliferation in this organs.

PMID- 9011200
TI  - [Polychromatic kinetics of conformational and spin relaxation of reduced
      intermediates of myoglobin].
AB  - Moessbauer spectroscopy was used to study the relaxation of a non-equilibrium
      myoglobin state produced at 77 K by reduction of metmyoglobin Fe(III) with
      thermalized electrons. The intermediate is characterized with the metMb (r)
      conformation of the protein globule and a low spin heme Fe(II) with a water
      molecule on the sixth coordination site. The intermediate is stable at 77 K but
      relaxes with increasing temperature into equilibrium deoxymyoglobin with
      dissociation of the bond Fe(II)-H2O and the transition of the Iron into the high
      spin state. In the temperature range 147-195 K the relaxation kinetics is
      nonexponential in time and can be described in terms of the polychromatic
      kinetics. A fitting of the kinetics data supposing a gamma-distribution of
      activation enthalpies of the relaxation shows a shift and a narrowing of the
      distribution at T > 180 K. The effect of structural rearrangements and
      equilibrium conformational fluctuations in the protein on the shape of the
      observed barrier distribution is discussed.

PMID- 9011201
TI  - [The future of quinolones].

PMID- 9011202
TI  - [Coinfection by mycobacteria in HIV-positive patients].
AB  - BACKGROUND: The aim of this study was to describe the clinical characteristics
      and therapeutic management of coinfection by mycobacteria in the authors
      hospital. METHODS: Two cases of coinfection detected in mixed cultures in agar
      7H11 or simultaneous positive cultures in several evaluable clinical samples
      (blood cultures for MAI and M. kansasii and sputum or stools for M.
      tuberculosis). RESULTS: One coinfection by MAI and M. tuberculosis and another by
      MAI and M. kansasii in two severely immunosuppressed HIV positive patients with
      less than 0.010 CD4 lymphocytes/10(9)/l. The clinical manifestations were
      unspecific, with fever and deterioration of the general state predominating over
      the 30-45 days of evolution. One of the patients improved with treatment which,
      in both cases, included a macrolide. Survival was very short and death was by
      intercurrent causes. CONCLUSIONS: For the diagnostic of coinfection in severely
      immunosuppressed patients multiple organic samples should be taken and
      appropriately processed to detect the mixed cultures or the presence of different
      mycobacteria in different samples from the same patients. Although the diagnosis
      of the species is fundamental, the empiric treatment of a disease by mycobacteria
      in severely immunosuppressed patients should include at least: ethambutol and
      clarithromycin or azithromycin in addition to other first line tuberculostatic
      drugs until definitive identification.

PMID- 9011203
TI  - [Uptake of 5 fluoroquinolones into human polymorphonuclear cells].
AB  - BACKGROUND: A comparative evaluation of the intracellular penetration of
      norfloxacin, ofloxacin, levofloxacin, fleroxacin and lomefloxacin was carried out
      in human polymorphonuclear leucocytes (PMNs). METHODS: The fluorometric method
      was used based on the natural fluorescence of some fluoroquinolones. RESULTS: All
      the fluoroquinolones accumulated within the human polymorphonuclear leucocytes
      achieving a quotient of between 4 to 6 in intracellular and extracellular
      concentration (I/C) with no significant differences being observed between the
      two. Penetration was rapid and was not saturable within the intervals of
      extracellular concentrations tested. The intracellular penetration of these
      fluoroquinolones was dependent on temperature and cell viability was altered in
      only levofloxacin and norfloxacin. The I/E values obtained significantly
      decreased when the cells were incubated at 4 degrees C. These values showed an
      important increase to pH 5 and decreased to pH 9, with this pH being
      statistically significant only in ofloxacin. CONCLUSIONS: All the
      fluoroquinolones evaluated penetrated rapidly into the phagocytic cells achieving
      intracellular concentrations which were several fold higher than the
      extracellular concentrations, with no notable differences being observed being
      the two, thus providing an additional advantage for their use in infections
      produced by microorganisms capable of surviving intracellularly.

PMID- 9011204
TI  - [Microbiological study of some microorganisms implicated in sexually transmitted
      diseases among the female prison population].
AB  - BACKGROUND: Sexually transmitted diseases (STD) are of over greater interest,
      particularly since the appearance of the human immunodeficiency virus ( HIV) in
      the last decade. Asymptomatic or oligosymptomatic infections are very frequent,
      overall in women. The aim of this study was to know the prevalence of certain STD
      producing microorganisms in a female penitentiary population, the clinical
      characteristics and evaluate the risk factors which may be found in this
      population. METHODS: One hundred thirty-three female prisoners attended in the
      Gynecology Ward of the Female Penitentiary of Carabanchel of Madrid, Spain, were
      studied over 13 months (from 30 April 1993 to 30 May, 1994). Vaginal and
      endocervical samples were taken in each case for microbiologic study by the usual
      methods. Demographic and clinical data were collected as were possible risk
      factors for acquiring STD (age of first sexual relations, sexual habits,
      intravenous drug addiction.

PMID- 9011205
TI  - [Pyogenic osteomyelitis after a plantar puncture wound: analysis of a series of 8
      cases].
AB  - BACKGROUND: The aim of this study was to know the incidence of osteoarticular
      infection secondary to plantar puncture, in the authors' center, and review the
      clinical characteristics, diagnosis and treatment. PATIENTS AND METHODS: A
      retrospective analysis of the cases of osteomyelitis and/or pyogenic arthritis
      secondary to plantar puncture admitted from 1986 to 1994 in the authors'
      hospital. RESULTS: Eight cases of osteoarticular infection secondary to plantar
      puncture (all males with a mean age of 37.2 years) were analyzed with a
      prevalence of 1.65% out of the total number of plantar punctures attended in the
      emergency department. The mechanism of the wound was, in all the cases, that of
      stepping on a nail. The most frequent clinical manifestations were pain and signs
      of local inflammation. Systemic repercussion was not observed in any case. A
      monomicrobial culture was obtained in 6 cases (in five P. aeruginosa was
      isolated). Combined surgical and antibiotic treatment was performed in 7
      patients. A foreign body was found in only one case. The mean length of
      antibiotic treatment was five weeks. CONCLUSIONS: Initial surgical treatment of
      plantar punctures is fundamental, in addition to home instructions and follow up
      to avoid late severe infectious complications. The role of radiology and other
      diagnostic imaging techniques should be considered to detect foreign bodies. The
      role of prophylatic antibiotics is controversial but may be indicated in certain
      cases.

PMID- 9011206
TI  - [Urinary tract infection caused by Haemophilus spp. in pediatrics: a rarely
      studied disease].
AB  - BACKGROUND: Haemophilus influenzae and Haemophilus parainfluenzae have been, in
      very seldom times, described as a cause of urinary tract infection (UTI), mainly
      on adults. Their real incidence has been scarcely studied. In view of this
      situation, we have investigated the cases occurred during the year of 1994 in our
      hospital, in Cadiz (Spain). METHODS: A total of 16,446 urine cultures from in
      patients and ambulatory patients were processed, including the chocolate agar
      medium in the cultures. RESULTS: Urinary infection by Haemophilus supposed an
      incidence of 0.27% with respect to all positive urine cultures, and a 0.88% of
      the paediatric ones. H. influenzae was isolated in 7 occasions, and H.
      parainfluenzae in 3 of them. The 80% of the cases of UTI corresponded to
      paediatric patients. CONCLUSIONS: It would be convenient the inclusion of
      chocolate agar medium in the urine cultures for determined patients, chiefly on
      children.

PMID- 9011207
TI  - [Is sputum study useful in the etiological diagnosis of community-acquired
      pneumonia?].

PMID- 9011208
TI  - [Antifungal resistance in opportunistic pathogenic fungi (II). Imidazoles and
      triazoles].

PMID- 9011209
TI  - [Persistent fever, retroperitoneal adenopathies, pancytopenia, and
      hepatosplenomegaly in an African immigrant with HIV-1 infection].

PMID- 9011210
TI  - [Acute abdomen and pulmonary nodules in a kidney transplant recipient].

PMID- 9011211
TI  - [Macrolide antibiotics: Streptococcus pneumoniae and Haemophilus influenzae].

PMID- 9011212
TI  - [Pneumonia caused by Pneumocystis carinii in a drug addict without evidence of
      HIV infection].

PMID- 9011213
TI  - [Endophthalmitis caused by Aeromonas sobria].

PMID- 9011214
TI  - [Evaluation of a reagent for the diagnosis of Epstein-Barr virus infection].

PMID- 9011215
TI  - [Vertebral osteomyelitis caused by Salmonella typhimurium].

PMID- 9011216
TI  - [Non-pneumonia lower respiratory infection by Neisseria meningitidis].

PMID- 9011218
TI  - [Corynebacterium CDC G1: pathogen or colonizer?].

PMID- 9011217
TI  - [Infectious endocarditis caused by Escherichi coli].

PMID- 9011219
TI  - [Bacteremia caused by Vibrio vulnificus in a patient with a skin ulcer exposed to
      sea water].

PMID- 9011220
TI  - [Bacteremia caused by Anaerobiospirillum succiniciproducens associated with
      paralytic ileus].

PMID- 9011221
TI  - [Disseminated sporotrichosis in a patient with chronic hepatopathy and
      hepatocarcinoma: report of a case].

PMID- 9011222
TI  - [Sudden death as the presenting form of an infectious pathology in the emergency
      service letter)].

PMID- 9011223
TI  - Characterization of phthalate plasticizers by HPLC/thermospray mass spectrometry.

PMID- 9011224
TI  - [Studies of in vitro and in vivo derived 1,2-diazetine and nitronylnitroxide as
      donors and acceptors of nitric oxide].
AB  - The series of nitronylnitroxyl radicals (NNR) were studied as paramagnetic
      scavengers of nitric oxide. These radicals react with NO with rate constants of
      (0.6-1.1).10(4) M-1.sec-1 forming stable iminonitroxyl radicals. They can be used
      to assay nitric oxide in solutions by EPR spectroscopy; the sensitivity of the
      method is 1 microM for the detection of NO concentration and 0.3 nM/sec for the
      measurements of the rates of NO generation for 1 h in 0.2 ml sample. To overcome
      fast reduction of the radicals in biological samples, charged NNR was
      incorporated into the inner volume of large unilamellar phosphatidylcholine
      liposomes thus decreasing the rates of NNR reduction about 1000-fold. The method
      was used for the NO synthase activity assay in rat cerebellum cytosol. NNR was
      used to study the kinetics of the decomposition of 3,4-dihydro-1,2-diazete 1,2
      dioxides (DD). Several DD derivatives at 5-80 microM concentrations are very
      effective vasodilators in perfused rat tail artery. Intraperitoneal injection of
      several DD (40-200 micrograms/kg weight). in hereditary hypertensive rats (ISIAH
      strain) significantly (by 30%) decreased systolic arterial blood pressure whereas
      similar effect of trinitroglycerin was detected at significantly higher dose (900
      micrograms/kg weight).

PMID- 9011225
TI  - [Amino acid sequence of anionic protease inhibitors from buckwheat seeds].
AB  - Complete amino acid sequence of IT1 protease inhibitor and partial amino acid
      sequences of IT2 and IT4 protease inhibitors from buckwheat Fagopyrum esculentum
      Moench seeds were determined by automatic Edman degradation and mass
      spectrometry. IT1 inhibitor comprises 69 amino acid residues and its molecular
      mass is 7743.8 D. N-terminal 48 amino acid residues of IT2 inhibitor are
      identical to similar sequence of IT1 inhibitor. The sequence of 10 amino acid
      residues of IT4 inhibitor is completely identical to a part of the sequence of
      IT1 inhibitor C-terminally adjacent to its active site. Analysis of amino acid
      sequences of IT1, IT2 and IT4 inhibitors suggests that the proteins are the
      members of the potato proteinase inhibitor 1 family and include Arg-Asp residues
      in their active site.

PMID- 9011226
TI  - [Modification of the histidine in rat skeletal muscle deaminase by
      diethylpyrocarbonate].
AB  - Diethylpyrocarbonate inactivated rat skeletal muscle AMP deaminase in 10 mM
      phosphate buffer, pH 6.5, at 23 degrees with the second order rate constant of
      580 M-1.min-1. Absorbtion at 240 nm was concomitantly increase. Enzyme activity
      can be restored by hydroxylamine. The pH-dependence of inactivation indicates the
      involvement of a group with pKa 6.9. The data suggest that modification of one
      histidyl residue per subunit inactivates the activity of tetrameric AMP
      deaminase.

PMID- 9011227
TI  - [Expression of functionally active hyman cytochrome P-450c21 (CYPXXIA2) in
      Escherichia coli and single-stage purification of it using metal-affinity
      chromatography].
AB  - Active human cytochrome P-450c21 was expressed in Escherichia coli and purified
      to homogeneity. To increase expression, cDNA encoding for the N-terminal fragment
      of cytochrome P-450c21 was modified. Four histidine codons were added to cDNA
      encoding for the C-terminus of the protein; thus, recombinant protein could have
      been rapidly and effectively purified by metal-affinity chromatography. Modified
      human cytochrome P-450c21 was expressed (40-50 nmoles/l of culture according to
      spectrophotometry) which was able to bind to bacterial membrane. Modifications of
      N- and C-terminal regions of cytochrome P-450c21 did not change Km and Vmax for
      hydroxylation of progesterone and 17 alpha-hydroxyprogesterone in reconstituted
      system. Recombinant cytochrome P-450c21 was purified to apparent homogeneity from
      Escherichia coli membrane extract by metal-affinity chromatography. Purified
      cytochrome P-450c21 migrates as a single 54 kD band on polyacrylamide gel and
      exhibits type I spectral changes during interaction with progesterone and 17
      alpha-hydroxyprogesterone. Activity of purified cytochrome P-450c21 was
      reconstituted with mouse liver microsomal NADPH-cytochrome P-450-reductase and
      NADPH-regenerating system. Purified enzyme had Km 12.2 and 3.21 microM and Vmax
      192.9 and 198 nmoles/min/nmole of P-450c21 for 17 alpha-hydroxyprogesterone and
      progesterone, respectively. According to titration spectra, dissociation
      constants for progesterone and 17 alpha-hydroxy-progesterone were 14.7 and 31.1
      microM, respectively.

PMID- 9011228
TI  - [Participation of inducible stress-proteins in realizing the cardioprotective
      effect of Rhodiolae rosea].
AB  - The effects of the Rhodiolae rosea extract on contractility of rat hearts
      isolated by the Langendorff's technique, creatine phosphokinase activity in the
      perfusate, and induction of myocardial stress protein synthesis (hsp-70) were
      studied after total ischemia and reperfusion. The adaptogen produces
      cardioprotector effects and prevents ischemia- and reperfusion-induced
      contractility aberrations. The possible role of inducible stress proteins (hsp
      70) in these effects is discussed.

PMID- 9011229
TI  - [Stimulation of mitochondrial respiration, induced by laser irradiation in the
      presence of rhodamine dyes].
AB  - The effect of micromolar concentration of rhodamine 123 (methylrhodamine) and
      ethyl and amyl esters of unsubstituted rhodamine on oxygen consumption by rat
      liver mitochondria was studied under irradiation by an argon laser (488 and 514
      nm). Irradiation of mitochondria in the presence of rhodamine stimulates their
      respiration. Light-induced stimulation of respiration is not inhibited by free
      radical scavenger ionol and by inhibitor of the permeability transition pore
      cyclosporine A. Stimulation of respiration by moderate doses of radiation is
      reversed in the dark. Increase in radiation dose resulted in only partial
      reversal of stimulated respiration in the dark. Rhodamine efficacy in stimulation
      of mitochondrial respiration depends on its structure (amyl > ethyl >
      methylrhodamine).

PMID- 9011230
TI  - [Methemalbumin--a biocatalyst of aromatic amine oxidation by hydrogen peroxide].
AB  - The kinetics of hydrogen peroxide-dependent oxidation of 3,3',5,5'
      tetramethylbenzidine (TMB) and o-phenylenediamine catalyzed by hemin and hemin
      bovine serum albumin (BSA) complex (methemalbumin) was studied in buffered
      physiological solution containing dimethylformamide (40%) and dimethyl sulfoxide
      (2%), respectively. The formation of hemin-BSA complex enhanced hemin catalytic
      activity in oxidation of both amines. The reaction follows first-order kinetics
      in biocatalyst concentrations, H2O2, and H+ ions from pH 6.5 to 9.0. The
      catalytic constants, Michaelis constants, and kcat/K(m) ratios for both
      substrates in hemin- and methemalbumin-catalyzed reactions were calculated using
      double reciprocal plots of the effect of the initial TMB and PDA concentrations
      on the initial reaction rates. Mechanism of radical oxidation of amines in hemin
      H2O2 and hemin-BSA-H2O2 systems is discussed. Both systems can effectively
      initiate radicals free radicals formation; their activity is similar to the
      previously studied ferritin-H2O2 system.

PMID- 9011232
TI  - [Two site-specific endonucleases from the thermophilic OV Bacillus species
      strain].
AB  - Two site-specific endonucleases, BspOVI and BspOVII, were isolated from a
      thermophilic strain Bacillus species OV. The activities of both enzymes are
      maximal at 48 degrees C and do not depend on ATP and S-adenosyl-L-methionine.
      BspOVI recognizes the sequence [sequence: see text] and cleaves it as indicated
      by arrows. Thus, BspOVI is a IIN-subclass endonuclease isoshizomer of Eam1105I.
      BspOVI is very stable during storage. The enzyme can be used for direct T/A
      cloning of PCR products. BspOVII recognizes and cleaves the sequence [sequence:
      see text]; thus, BspOVII is an isoshizomer of CIaI. The cleavage by BspOVII is
      blocked by dam methylation of adenine inside the recognition site.

PMID- 9011231
TI  - [Metabolic and structural properties of extrachromosomal DNA in mammalian cells].
AB  - Discrete bands of free DNAs of approximately 25 kbp were detected in human cell
      cultures. According to electrophoretic shifts induced by single and double strand
      breaks, they from topological isoforms (supercoiled, open, and linear). Long-term
      labeling (24 h) of growing and quiescent cultured cells by [3H]thymidine
      indicates differences of free versus chromosomal DNAs including (i) significantly
      lower specific radioactivity in growing cells, (ii) higher specific radioactivity
      in quiescent cells, and (iii) resistance to fluorodeoxyuridine labeling. During
      apoptosis of cultured Namalwa cells, heterogeneous fragments are formed which
      differ from free DNAs. Crosslinking of nascent RNA with DNA template by 8
      methoxypsoralen indicated slight transcriptional activity of free DNAs.

PMID- 9011233
TI  - [Activity of basic arginine- and lysine-residue cleaving carboxypeptidase in rats
      of various ages].
AB  - Activities of basic carboxypeptidases (CP) in rat brain regions and peripheral
      tissues were determined on postnatal days 0-90. The highest phenylmethylsulfonyl
      fluoride-inhibited activity was detected immediately after birth; activity
      decreases on day 10 with subsequent increase on day 20 and decrease on day 90.
      The CPE activity was the lowest immediately after birth, increased on day 30, and
      decreased on day 90. The lysosomal CPB activity was highest at birth and on day
      90 and was the lowest on day 20. The activity of CPN slowly increases till day 20
      and then it decreases. The relationship between dynamics of basic CP activity in
      ontogenesis and functional role of these enzymes is discussed.

PMID- 9011234
TI  - [Effect of anti-tumor agents cisplatin and cycloplatam on membrane protein kinase
      C activity in murine T-lymphocytes].
AB  - The effect of cisplatin and the new drug cycloplatam (amine (cyclopentylamine)-S
      (-)-malatoplatinum (II)) on protein kinase C (PKC) activity and Ca(2+)-dependent
      binding of PKC to T lymphocytes membranes was studied in vivo and in vitro. At
      first, the effect of the drugs on PKC activity of intact and activated
      lymphocytes was studied in vivo. In 48 hours after intraperitoneal injection of
      mice with therapeutic doses of the drugs, PKC activity of intact lymphocytes was
      differentially affected. Cisplatin did not practically alter the enzyme activity,
      whereas cycloplatam inhibited the PKC activity by 37% versus control. In
      lymphocytes activated by mouse P-388 leukemia cells in vivo, the drugs caused
      almost complete suppression of PKC activity and Ca(2+)-dependent binding of the
      enzyme to the membranes. The drugs were effective in intact cells. After
      incubation of intact lymphocytes in vitro for 24 hours with cisplatin or
      cycloplatam (10(-5)M), PKC activity was increased 1.62- and 1.35-fold,
      respectively, versus control. Ca(2+)-dependent binding of the enzyme to the
      membranes was also increased 1.61- and 1.36-fold by cisplatin and cycloplatam,
      respectively. On the contrary, at 10(-4) M concentration under similar
      conditions, the drugs did not affect the PKC activity of the lymphocytes.
      Furthermore, cycloplatam, unlike cisplatin, reduced the PKC binding to cellular
      membranes by 31%. The mechanisms of the drugs effects on PKC activity are
      suggested. The data indicate that increase or decrease of PKC activity induced by
      the drugs cause stimulation or depression of functional activity of T
      lymphocytes, respectively. Thus, the membrane-bound PKC can play the key role in
      initiation and development of immunomodulatory effects of cisplatin and
      cycloplatam.

PMID- 9011235
TI  - [Trypsin and microbial serine proteinase inhibitors isolated from Yersinia
      pseudotuberculosis].
AB  - A novel 9 kD protein inhibitor of trypsin and related proteinases was purified
      from culture filtrate of Yersinia pseudotuberculosis by ultrafiltration, affinity
      chromatography, and gel filtration. The protein is stable at pH from 1 to 9. The
      inhibitor activity dramatically decreases at temperature above 37 degrees C. The
      purified inhibitor significantly suppresses activities of an endogenous trypsin
      related proteinase and trypsin but does not affect chymotrypsin, pepsin, and
      papain. One molecule of yersinia inhibitor binds two molecules of endogenous
      trypsin-related proteinase and about one trypsin molecule. The Ki for yersinia
      proteinase is 1.7.10(-7) and Ki for trypsin is 2.4.10(-7). Amino acid composition
      of the inhibitor is characterized by the presence of beta-aminobutyric acid and
      ornithine and relatively high contents of alanine and arginine whereas cysteine,
      histidine, and proline are absent.

PMID- 9011236
TI  - [Purification and properties of isocitrate lyase and malate synthase from fasting
      rat liver].
AB  - Key enzymes of glyoxylate cycle, isocitrate lyase and malate synthase, are active
      in the fasting rat liver. The enzymes were synthesized on day 3 after food
      deprivation and their activities were maximal on day 5 of fasting. Specific
      activity of isocitrate lyase was 0.06 units/mg protein and specific activity of
      malate synthase was 0.03 units/mg protein. Isocitrate lyase was isolated and
      purified by ammonium sulfate fractionation, DEAE-cellulose chromatography and
      Toyopearl HW-65 gel filtration. Enzyme was purified to specific activity of 9.0
      units/mg protein with 8.2% yield. Molecular mass of isocitrate lyase was 145 kD
      according to gel filtration. Catalytic characteristics of isocitrate lyase
      indicate that the enzyme follows Michaelis-Menten kinetics (Km for isocitrate is
      0.07 mM), is competitively inhibited by glucose-I-phosphate (Ki = 1.1 mM) and
      glucose-6-phosphate (Ki = 1.9 mM), and is activate by ADP; optimal pH is 7.4.
      Malate synthase was partially purified by ammonium sulfate fractionation and
      Sephadex G-25 gel filtration. Enzyme was purified to specific activity of 0.15
      units/mg protein with 45% yield. Km of malate synthase for acetyl-CoA was 0.2 mM
      and Km for glyoxylate was 0.3 mM; optimal pH was 7.6.

PMID- 9011237
TI  - [X-ray structural analysis of RNA-protein complexes].

PMID- 9011238
TI  - [A new site-specific adenine DNA-methyltransferase from Bacillus species ST5].
AB  - The site-specific DNA-methylase M.BspST5I has been isolated from Bacillus species
      ST5 and purified to functional purity. M.BspST5I protects DNA from endonuclease
      R.BspST5I which recognizes the nonpalindromic sequence [formula: see text] on
      DNA. MpBspST5I belongs to adenine-specific methylases.

PMID- 9011239
TI  - [Glutathione S-transferase P1-1 in normal and cancerous lung tissue: properties,
      function, and possible mechanisms for regulating activity].
AB  - Different forms of one of the enzymes catalyzing the xenobiotic metabolism,
      glutathione S-transferase P1-1 (GST P1-1), purified from normal and tumoral lung
      tissues, are described. Statistically significant (p < 0.05) increasing of enzyme
      activity in tumour, as compared with normal tissue, is shown. Molecular weights
      and isoelectric points of the enzyme two forms were characterized. Statistically
      significant increasing in the concentration of fatty acids with C = 18 bound to
      GST P1-1 in tumour tissues, was demonstrated. The possibility of regulation of
      GST P1-1 activity, as well as the level of its phosphorylation on serine and
      threonine, under the influence of the epidermal growth factor, is shown.

PMID- 9011240
TI  - [Identification and some properties of cattle splenocyte nucleus phosphoprotein
      phosphatase activatorin various tissues].
AB  - An activator of phosphoprotein phosphatase from bovine spleen cell nuclei has
      been isolated from different tissues (rat liver, bovine liver, spleen and
      kidney). The activator increases the enzyme activity by a factor of 4-5. The
      activator is heat-stable (it withstands incubation at 95 degrees C for 10 min)
      but loses its activity by 50% in 6-7 hrs at 4 degrees C.

PMID- 9011241
TI  - [Complex formation between alpha-chymotrypsin and block copolymers based on
      ethylene and propylene oxide, induced by high pressure].
AB  - A new method of formation of non-covalent adducts based on an amphiphilic diblock
      copolymer of ethylene and propylene oxides with molecular mass of 2 kDa and alpha
      chymotrypsin (ChT) under high pressure, has been developed. The composition of
      the complexes corresponds to seven polymer molecules per one ChT molecule in the
      pressure range of 1.1 to 400 MPa. The complexes fully retain the catalytic
      activity. Kinetic constants (Km and kcat) for enzymatic hydrolysis of N-benzoyl-L
      tyrosine ethyl ester catalyzed by the complexes are identical with the
      corresponding values for native ChT. Analysis of kinetics of thermal inactivation
      of the complexes revealed that the constant of the rate of the slow inactivation
      step is markedly lower than for ChT.

PMID- 9011242
TI  - [HMG 14--a physiological substrate for casein kinase NII of neuronal chromatin].
AB  - The "in vivo" effects of antifeins on casein kinase NII from rat brain neuronal
      chromatin have been investigated. Injection of antifeins into rats resulted in
      changed in cAMP-independent phosphorylation of HMB 14 by casein kinase NII. No
      changes in HMB 17 phosphorylation were found. Casein kinase NII was isolated and
      purified from rat brain neuronal chromatin. It was established that casein kinase
      phosphorylates HMG 14 (but not HMB 17) from rat rain cells and calf thymus as
      effectively as do exogenous substrates, phosvitin and casein. The Km values for
      HMB 14 and HMB 17 from brain cells are 5.1 and 180.5 mumol, respectively.
      Antifeins do not influence casein kinase NII, when HMB 17, phosvitin and casein
      are used as substrates. HMG 14 phosphorylation changed significantly under the
      action of antifeins (10(-8)-10(-6) M). "In vivo" and "in vitro", some antifeins
      increase, and others reduce phosphorylation of HMB 14 by casein kinase NII. This
      correlates with their action on the transcription and long-term memory. The role
      of casein kinase NII and its physiological substrates in regulation of chromatin
      transcription is discussed.

PMID- 9011243
TI  - [UV-crosslinking of the globular domain of histone H1 with DNA in
      deoxyribonucleoprotein].
AB  - UV-irradiated DNP was digested by trypsin to cleave histones, and a crosslinked
      DNA-peptide complex was isolated. The globular domain of histone HI was found to
      be linked to DNA. The resistance of the globule to trypsinolysis is discussed
      with regard to chromatin structure.

PMID- 9011244
TI  - [Use of aerosol A-300 amd GF/F (GF/C) filters for purifying fragments of DNA,
      plasmid DNA, and RNA].
AB  - Aerosil A-300 and GF/F (GF/C) filters were used for purifying plasmid DNA and
      intact RNA as well as for the recovery of DNA fractionated on agarose gels. In
      the presence of guanidinium thiocyanate Aerosil A-300 and GF/F (GF/C) filters
      selectively bind nucleic acids, while proteins, agarose polysaccharides and salts
      are washed off. Nucleic acids desorbed from the Aerosil and filters are available
      immediately as substrates: DNA for restriction analysis, ligation and sequencing;
      RNA--for RT-PCR.

PMID- 9011245
TI  - [Isolation and characteristics of ekamulin--a prothrombin activator from
      multiscaled viper (Echis multisquamatus) venom].
AB  - Ecamulin, a novel prothrombin activating enzyme, has been isolated and purified
      63-fold with a 57% yield from the venom of the Middle-Asian sand viper Echis
      multisquamatus using three-step ion-exchange chromatography. The enzyme was shown
      to activate prothrombin similarly to Ecarin, a prothrombin-converting enzyme from
      Echis carinatus venom, however, differing from the latter by structural and
      physico-chemical properties. The enzyme is a Zn-proteinase: it contains 1 mol Zn
      per 1 mol of protein. The molecular mass of the enzyme as determined by Sephacryl
      S-200 chromatography is 93 +/- 2 kDa. Upon SDS-PAAG electrophoresis ecamulin
      produces two bands with Mr of 67 and 27 kDa under non-reducing conditions, and
      three bands with Mr of 67, 14 and 13 kDa in the presence of DTT. During native
      PAGE without SDS, the activator yields one slow mobility band: two bands are
      observed after addition of DTT or EDTA. Carbohydrates containing N-acetyl-alpha-D
      glucosamine residues are localized in the 67 kDa chain. Ecamulin has two
      isoforms, S2 and S3, that are distinguished by the charge and partial coagulation
      activities: form S2 has 250 NIH units/mg, while the S3 form has 524 NIH units/mg.
      The amino acid sequences of the both isoforms are similar but the more active S3
      form has 4 times higher content of Gln and 4 times less of Gly than the S2 form.
      The isoelectric point is 4.3-4.5; E280 of 1% solution is 10.2. Forms S2 and S3 of
      ecamulin hydrolyze chromogenic substrates of plasma kallikrein S2302 and
      glandular kallikrein 2266. Ecamulin does not hydrolyze BAEE, TAME, LEE, thrombin
      substrates Chromozym TH and S2160, factor Xa-S2222, protein Ca-Chromozym PCa and
      Plasmin S2251. The amidase activity is nonreversibly inhibited by EDTA, o
      phenanthroline (the activity is recovered by addition of Zn2+), Cys or DTT, EGTA,
      DFP, PMSF or pCMB do not inhibit the enzyme activity. Ecamulin converts
      prothrombin to alpha-thrombin passing by a shunt via the meizothrombin stage. The
      reaction of prothrombin activation does not require Ca2+, phospholipids of factor
      Va. Part of this work was presented at the International Conference "Fibrinogen
      and fibrinolysis", Yalta, September 23-28, 1995.

PMID- 9011246
TI  - [Natural substrates of uridylylpolynucleotide-(5'P--->O)-tyrosine
      phosphodiesterase--an enzyme, hydrolyzing the covalent bond between RNA and
      picornaviral VPg and a synthetic model of them].
AB  - A phosphodiester derivative of 3,5-[125I]diiodotyrosine and 5'
      [32P]oligodeoxynucleotide mimicking a natural compound--the picornaviral RNA Pg
      complex--was obtained by the method of active N-hydroxybenzotriazole
      phosphodiesters. Using the isotope iodine ion exchange reaction in the tyrosine
      residue, the specific activity of the model compound could be increased 50 times.
      It has been found that the unlinking enzyme does not hydrolyze the phosphodiester
      bond between the tyrosine residue and the oligodeoxynucleotide. Treatment of
      viral RNA-VPg by nuclease S1 gave a 5'-terminal fragment of RNA linked with the K
      peptide. This fragment was shown to be split at a higher rate in comparison with
      the original compound, RNA-VPg. A two-step procedure for obtaining picornaviral
      RNA-KpA-Kp and RNA-VPg compounds with higher specific activity selectivity
      labelled at the protein fragment with 125I was developed. At the first stage,
      aliphatic amino groups of the polypeptide within the RNA-VPg or RNA-Kp complex
      were selectively acylated by the activated ester of hydroxyphenylpropionic acid,
      whose residue was iodinated at the second stage by radioactive NaI in the
      presence of chloramine T. The specific radioactivity of the thus labelled
      compounds exceeded 15 to 30 times the specific activity upon selective
      introduction of the label into the protein with the help of the Bolton-Hunter
      reagent. The method can be used for highly effective and selective introduction
      of the label into the protein fragment of other nucleoproteins simultaneously at
      the amino groups of the protein and at tyrosine residue.

PMID- 9011247
TI  - [Isolation and properties of serine proteinase PC from the Kamchatka crab,
      Paralithodes camtschatica--a proteolytic enzyme with broad specificity].
AB  - A homogeneous serine proteinase PC has been isolated from the Camchatka crab
      (Paralithodes camtschatica) hepatopancreas using affinity chromatography on
      arginine-Sepharose, protamine tryptic peptide-agarose and ion-exchange
      chromatography on Mono-Q, with a 68% yield. The enzyme is completely inhibited by
      diisopropylfluorophosphate, a typical inhibitor for serine proteinases. The
      molecular mass of the proteinase is 29 kDa, pI is 3.0. The proteinase splits Glp
      Phe-Ala-pNA optimally at pH 7.5 and 47-55 degrees C; Km is 0.83 mM, kcat is 67 s
      1. The enzyme is stable at pH 4-9. Proteinase PC possesses a broad substrate
      specificity and splits the peptide bonds formed by the carboxyl group of
      hydrophobic amino acids, arginine and lysine, in peptides and proteins. The
      enzyme hydrolyzes fibrin and collagen. Its N-terminal sequence, IVGGQEATP,
      reveals a 90% homology with analogous sequences of collagenolytic proteinases
      from other crab species.

PMID- 9011248
TI  - [Conformation properties of heme-containing proteins using spin labels].
AB  - The review briefly summarizes the results of spin-label studies of conformational
      transitions in monomeric globins (myoglobin, leghemoglobin, erythrocruorin) as
      well as in another heme-containing protein, cytochrome c, induced by heme ligands
      and pH. In contrast with integral methods of investigation, for proteins with a
      known spatial structure the use of the spin-labelling technique makes it possible
      to obtain information on the conformational behaviour of the isolated parts of
      the protein structure which, alongside with the results obtained by other physico
      chemical methods, allows a conclusion on the nature of conformational movements
      in the protein during its functioning. The experimental results fit well into the
      model which represents a Mb-like structure as composed of three independent rigid
      helical fragments: AE(ABCDE), F and GH, whose reciprocal arrangement is
      controlled by N- and C-terminal salt bridges. Synchronous displacement of the
      above fragments relative to one another, which is due either to the ligand
      attachment and structural changes in the heme complex or to disturbances in ionic
      interactions at the N- and/or C-end(s) of the structure under effect of pH or
      allosteric effectors, might serve as a structural basis for homo- and
      heterotropic regulation in hemoglobin. Similarly, the spin label method allows
      for tracing and obtaining important information about local conformational events
      in cytochrome c which in the native protein are associated with a change in pH in
      the range of 5-13 and are accompanied by the substitution of the heme sixth
      ligand, Met-80, by Lys-79 (pH 9.3), and then by Tyr-67 (pK 11.1). Local changes
      in the conformation and dynamic properties of native cytochrome c provide, if
      necessary, global changes in its structure upon alkaline denaturation. It was
      found that substitution of the heme protein ligand, Met-80, by the external
      ligand, cyanide, markedly alters the dynamic properties of the polypeptide chain
      segment 67-75 adjacent to Met-80.

PMID- 9011249
TI  - [Carbohydrate-carbohydrate interaction].
AB  - The review deals with the new area in biorecognition--the carbohydrate
      carbohydrate interaction. Seven experimental approaches are described that were
      used for detecting and investigating this phenomenon, with special reference to
      its mechanism and peculiarities, particularly, in comparison with other types of
      molecular interactions; some historical aspects are also considered. The whole
      body of experimental evidence published on carbohydrate-carbohydrate interaction
      by the end of 1995, is reviewed. A special chapter is dedicated to intercellular
      adhesion mediated or initiated by carbohydrate-carbohydrate recognition. The main
      peculiarities of carbohydrate-carbohydrate interaction are as follows. Monovalent
      interaction is so low affinity that it cannot be recorded by routine physical
      methods, such as NMR. However, if polyvalent ensembles of oligosaccharides (e.g.,
      two membranes with a high density of built-in glycolipids) come in contact, one
      can observe a specific Ca(2+)-dependent interaction which is inhibited by either
      EDTA antibodies against carbohydrates or by oligosaccharides. The
      carbohydrate/carbohydrate-mediated cell adhesion is a rapid primary process which
      immediately precedes carbohydrate-lectin (selective) and protein-protein
      (integrin) adhesion. Le(x)/Le(x)-Mediated compactization of embrions and Gm3/Gg3
      mediated adhesion of tumour cells provide illustrative examples of such
      intercellular contacts.

PMID- 9011250
TI  - [ob protein--product of expressing an obesity gene and some aspects of modern-day
      endocrinology].
AB  - A brief review of the studies on the obese (ob) gene is given. The ob gene is a
      mouse gene, the mutations of which are associated with altered metabolism and
      increased lipid deposits in adipose tissue. Recessive ob gene mutations in
      homozygous mice result in obesity and diabetes mellitus. Both mouse and human ob
      cDNAs were cloned and sequenced using positional cloning, exon trapping, and PCR.
      Of ten tested tissues, the ob gene was expressed only in white adipose tissue.
      The ob gene cDNA has a region of the nucleotide sequence with an opening reading
      frame and encodes the ob protein consisting of 167 amino acid residues. Mouse and
      human ob proteins showed a 85% homology. The 145-amino acid peptide termed as
      leptin and derived from ob protein after cleavage of signal peptide is secreted
      in the blood and stimulates fat consumption in energy metabolism. The
      biologically active ob peptide has been obtained by gene engineering methods.
      Administration of the ob protein to ob/ob mice reduced body weight and abolished
      symptoms of diabetes. The ob protein lowered body weight also in healthy animals.
      It was biologically effective both upon parenteral and intravenous administration
      and also when injected into lateral ventricle of the brain. With a polyclonal
      antiserum against the peptide the ob protein was shown to be present in human and
      mouse plasma and mouse adipose tissue. Based on the data obtained, it is
      postulated that the ob gene protein product leptin, is a hormone, which is
      secreted by adipocytes in the blood in varying amounts and regulates the mass of
      adipose tissue by stimulating lipid metabolism. Similarly to adipocytes, many
      other organs and tissues are presumably endocrine and may secrete peptide
      hormones in the blood. This considerably extends the scope of endocrinology and
      makes it necessary to review the existing concepts and views.

PMID- 9011251
TI  - [Effect of iron, zinc, and copper on lipid peroxidation in liver in vivo].
AB  - Changes in the levels of lipid peroxides, natural antioxidants (NA), iron, zinc
      and copper as well as the ability of the lipid substrate to oxidize in animal
      liver in the presence of iron, zinc and copper have been studied. It has been
      found that those metals increase the amplitude of natural fluctuations in iron,
      zinc and copper levels in the liver (by 5-30% in comparison with control). Within
      the first few hours following administration of iron and copper, the
      concentration of lipid peroxidation (LPO) products in animal livers increases,
      while the NA level and lipid oxidizeability decrease, in contrast. Zinc inhibits
      LPO in the liver within the first few hours following the injection. The changes
      in the content of NA, lipid oxidizeability and the level of LPO products in
      animal livers following iron, zinc and copper administration are phase-dependent.
      Data from regression analysis indicate a direct dependence (kcor = 0.98 at p < or
      = 0.05) between lipid oxidizeability and NA content in the liver following
      administration of iron, zinc and copper which, in turn, is suggestive of the lack
      of disturbances in the system of NA regulation

PMID- 9011252
TI  - [Effect of phospholipase A2 from Naja naja oxiana venom on activity of Na+,K+
      ATPase isoenzymes in rat brain].
AB  - The specific sensitivity of the isoforms of the rat brain Na+,K(+)-ATPase
      catalytic subunit to phospholipase A2 (PL A2) from Naja naja oxiana venom has
      been estimated on the basis of changes in the two-component dose response curve
      of ouabain inhibition of Na+,K(+)-ATPase activity. Moderate Na+,K(+)-ATPase
      inactivation of PL A2 is accompanied by a decrease of the apparent affinity for
      ouabain in comparison with the untreated enzyme without any significant changes
      in the isoform activity ratio in the preparation. This effect is eliminated by
      washing of the preparation with serum albumin and seems to be mediated by the
      effect of free fatty acids on the enzyme. At a high level of Na+,K(+)-ATPase
      inactivation, the alpha-isoforms is inactivated more rapidly than the alpha (+)
      isoform.

PMID- 9011253
TI  - Symposium on structure-based drug design. Rutgers, New Jersey, June 13-16, 1995.
      Proceedings and abstracts.

PMID- 9011254
TI  - 1st Joint Meeting of the International Cytokine Society and the International
      Society for Interferon and Cytokine Research. Geneva, Switzerland, 6-10 October
      1996.

PMID- 9011255
TI  - [Eliciting immune reactions using a suspension of immunosorbents].

PMID- 9011256
TI  - Strategies for the future in osteoporosis. Proceedings of a symposium. 9 December
      1995.

PMID- 9011257
TI  - [The relative effectiveness of setting goals as a chance for dealing with complex
      decision processes in medicine].
AB  - Beyond specialist aspects, decision making in medicine must also take ethical and
      economic considerations into account. Decisions according to the rational
      principle are orientated towards premisses with goals as a crucial part of them.
      Upon close examination, medical as well as ethical and economic premisses turn
      out to be uncertain, offering room for interpretation and procedural
      considerations. Simple algorithms of problem solution fail in complex decision
      situations especially if contradictory goals have to be considered and if a high
      potential of conflict exists. In complex problems, therefore, it is suggested to
      employ a three-step programme that consists of limiting the conflict by making
      the goals more precise and of handling the conflict by balancing different goals
      as first measures. As third step one could image a solution of the conflict by
      means of an evolution of different goals basing on the very uncertainty or
      relativity of goals.

PMID- 9011258
TI  - [The need for preventive measures. Need for preventive measures at any price?
      Attempt at an argument in favor of the need for prevention not only for economic
      reasons].

PMID- 9011259
TI  - [Occupation and illness].
AB  - 1. There are three kinds of work-related diseases: officially recognised
      occupational diseases; occupational diseases; work-related but unspecific
      diseases. 2. These unspecific diseases occur more often than would be by mere
      chance, among certain professional groups. 3. Cancer mortality may increase as a
      result of occupational cancer-promoting factors, whereas the overall mortality
      may be unaffected. 4. In such cases, the mortality of other diseases not related
      to the occupation, is diminished ("vicarious mortality"). 5. The overall cancer
      mortality is probably not greatly increased by professional influences. This
      mortality is nearly constant in males and tends to decrease in females. 6. A
      strong inequality of mortality rates has been found in various occupational
      groups. The reason for these discrepancies is unknown. 7. Mortality is most
      strongly related to the mental demands made on individuals by their profession.
      8. Death through accidents is six times more frequent in the general population
      compared with job-related accidents. 9. Health hazard due to occupation is low in
      relation to mortality, but marked in work-related diseases.

PMID- 9011260
TI  - [Quality assurance in medical care].
AB  - The demand for quality assurance in Germany's health care system has been on the
      increase since promulgation of the Germany Statutory Health Service Reform law.
      To control, to assure and to improve quality a vast array of different systems is
      used by health care providers. All these systems work in a similar manner. The
      desired level of quality is determined and compared with the actually achieved
      level. If a deviation of quality is observed, actions for quality improvement are
      instituted. However, there are some problems that make quality assurance a
      difficult problem. Since the level of quality is a result of a patient's
      individual evaluation it is very difficult to set a common level. Another problem
      is to find valid criteria to measure the degree of quality. Finally, further
      research is necessary to analyse benefits and costs of introducing a quality
      assurance system.

PMID- 9011261
TI  - [Hepatitis B prevention at a school for mentally handicapped patients].
AB  - Between 1988 and 1993 two female teachers of a school for mentally handicapped
      children in Osnabruck were infected with hepatitis B. Some of these children are
      hepatitis B virus (HBV) carriers. We offered from May 1994 through 1995 free
      information tests and vaccinations to children, parents and teachers to improve
      hepatitis B immunity. At the end of that time 65-70% of children and teachers
      were immune because of the vaccination, 6% because of an earlier hepatitis B
      infection. The paedagogic, hygienic, and medical problems related to the risk of
      infection are discussed, especially with regard to the new regulation in Lower
      Saxony and the new recommendation by the Permanent Committee for Vaccination
      Problems in the Federal Republic of Germany.

PMID- 9011262
TI  - [Blood and hair arsenic, lead and cadmium analysis of adults and correlation
      analysis with special reference to eating habits and other behavioral
      influences].
AB  - In the present work the background burden of arsenic (As), lead (Pb) and cadmium
      (Cd) was determined in blood (B) and hair (H) samples of male and female adults.
      The results were combined with personal data like food consumption habits and
      other confounding factors, and were evaluated by correlation analyses. As, Pb,
      and Cd determination was performed by atomic absorption spectrometry (AAS), using
      graphite-furnace AAS for the determination of Pb and Cd, and fluid injection AAS
      for the determination of As, respectively. All persons participating in this
      study were not unusually exposed to these elements, neither in their working
      places nor at home. As, Pb and Cd concentration in the B- and H-samples were in a
      very low range corresponding to similar data presented in the literature.
      Although the number of samples was too small for definite conclusions, the
      following significant correlations between the element concentration in B- and H
      samples as well as between the other confounding factors should be considered: H
      As depends on B-As; H-Pb depends on B-Pb; H-Pb corresponds to H-Cd; H-Cd, H-Pb
      distal > proximal; H-As distal < proximal; B-Cd, B-As, H-Pb in smokers > non
      smokers; H-As, B-Pb, H-Pb males > females; B-Pb positively correlated to wine
      drinking: B-Pb negatively correlated to daily consumption of mineral water; B-Pb
      positively correlated to daily consumption of vegetables; B-As positively
      correlated to fish consumption; B-Pb, H-Pb increase with increasing age of
      houses. Due to the low concentration of As, Pb and Cd found in the B- and H
      samples contamination must be regarded as high risk. The application of AAS for
      the metal determination in blood is generally accepted and has become a routine
      method for this purpose. The possibilities of contamination are well known and
      can be avoided. However, the element determination in hair samples by AAS bares a
      great risk of falsification by contamination, especially, when the determination
      is performed only in one or two hair samples of normally exposed individuals with
      very low element concentrations. On the other hand, when element determination is
      performed in sufficiently large numbers of hair samples (with the chance to
      neglect occasionally extreme values). AAS may be applied for element analysis in
      hair samples, too. It may be a vulnerable analytical method in research
      programmes of epidemiology and environmental toxicology.

PMID- 9011263
TI  - [Blood PCDD/F levels in blood of residents of a former cable incineration
      facility].
AB  - Increased levels of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofuranes
      (PCDF) were found in soil and roof dust of a residential area located near a
      metal reclamation plant in Northern Germany. In order to assess the degree of
      exposure of persons residing near to this plant, venous blood samples were
      collected from 14 subjects and analysed for PCDD/F and fat content. Furthermore,
      blood samples collected from the members of a farmer's family living nearby were
      analysed for PCDD/F. Previous studies had shown significantly increased PCDD/F
      levels in chicken eggs produced on this farm. Regarding the group of residents,
      the PCCD/F levels in blood fat were not increased when compared to background
      levels. However, some members of the farmer's family had increased PCDD/F levels
      in blood fat. The findings of these studies suggest that long-term consumption of
      contaminated animal products, especially chicken eggs, may result in increased
      PCDD/F levels in the body, whereas increased levels of PCDD/F in dust and soil do
      not noticeably affect the PCDD/F levels in human blood fat.

PMID- 9011264
TI  - [Limit values for polycyclic aromatic hydrocarbons in soil of children's
      playgrounds--basic criteria and recommendations].
AB  - Elevated concentrations of polycyclic aromatic hydrocarbons (PAK) are often found
      in the soil of former waste disposal sites, industrial areas, etc. It is
      desirable and useful to determine orientation values to facilitate and unify the
      evaluation of contaminations under the aspects of present or planned uses of an
      area, health protection and decision-making on remedial measures. In the present
      paper we wish to draw attention to, and discuss problems resulting from,
      particular characteristics of PAK, e.g. the toxicological property "complete
      carcinogens" or the necessity of taking into account oral, inhalative and dermal
      exposure of children on a playground. Based on the discussion, orientation values
      for benzo[a]pyrene and PAK ("normal" pattern) of 0.5 mg/kg soil and 5 mg/kg soil,
      respectively, are recommended for top soil of vegetation-free playgrounds. In
      comparison, deductions carried out by other working groups are presented.

PMID- 9011265
TI  - [Environmental concern of clients of an environmental medicine counseling
      center].
AB  - Environmental apprehensiveness and anxiety are often regarded as being
      responsible for unspecific health complaints in the context of environmental
      exposures if toxicological findings cannot explain them. However, there is a lack
      of empirical data on the influence exercised by environmental anxiety. A German
      adaptation of the American Environmental Worry Scale [1] was developed. The
      questionnaire has been used in a study on clients of the Consultation Centre for
      Environmental Medicine (CCEM). These clients (n = 51) were compared with a
      control group of clients of a vaccination centre (n = 238). As expected, the
      clients of the CCEM showed higher values of environmental worry. Moreover, the
      clients of the CCEM revealed scores of trait-anxiety which were more than one
      standard deviation above the level of the reference group. Environmental worry
      was weakly associated with a higher degree of trait-anxiety.

PMID- 9011266
TI  - [Incidence of enterohemorrhagic E. coli in meat].
AB  - In the period of August 1995 to January 1996 samples of beef and pork completed
      by raw sausages, were tested for enterohaemorrhagic strains of Escherichia coli.
      Samples were taken in a meat-processing company after mincing and cooling,
      delivered to the microbiological laboratory. All investigated meat originated
      from slaughterhouses which are EU-certified. In this study we found in no case
      enterohaemorrhagic strains of E. coli. Colony forming units were in the test
      10(5)/g meat in average.

PMID- 9011268
TI  - Being centered.

PMID- 9011267
TI  - [Criteria for cost saving in public health].

PMID- 9011269
TI  - In-sites: your computer link. Cyber happiness = a web site of our own!

PMID- 9011270
TI  - 15th European Workshop on Drug Metabolism. Jena, Germany, September 9-13, 1996.
      Abstracts.

PMID- 9011271
TI  - Neuromuscular disorders: gene location.

PMID- 9011272
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 9011273
TI  - [Teaching evolution of the working classification and nomenclature of
      rheumatism].

PMID- 9011274
TI  - [Formation and development of rheumatology in Russia].
AB  - The formation and development of rheumatology in Russia go back to February 4,
      1928, the date of setting up the Committee for Rheumatism Study and Control in
      the USSR at the RSFSR People's Commissariat of Health. Later the Committee was
      renamed the All-Union Antirheumatic Committee. The paper outlines the
      contribution of those who initiated to establish the Committee (M. P.
      Konchalovsky, G. M. Danishevsky, and others), analyzes the organizational
      structures for developing rheumatology and the evolution of teaching of
      rheumatism and other rheumatic diseases. It also gives some names of Russian
      scientists who made a great contribution to the development of rheumatology (V.
      T. Talalayev, M. A. Skvortsov, A. A. Kisel, A. I. Nesterov, N. D. Strazhesko, M.
      M. Diterikhs, M. G. Astapenko, V. A. Nasonova, etc.) and makes a brief review of
      the present status of rheumatology.

PMID- 9011275
TI  - [Rheumatism in the Russian Federation: statistic and reality].
AB  - According to the 1994 governmental statistics, 481353 patients with rheumatism
      (3.25 per 1,000 persons of all age groups) were notified in the Russian
      Federation. The prevalence of active rheumatism was 0.29%, that of chronic
      rheumatic heart disease was 2.96%. Among Russia's children, the spread of
      rheumatism was 0.8 per 1,000 children, the diagnosis of active rheumatism and
      chronic heart rheumatic diseases being made in 10,068 (31%) and 16,405 (0.5%)
      children. That of active rheumatism was first established in 12071 persons.
      Therefore, in 1994 primary incidence of acute rheumatic fever was 0.08 per 1,000
      inhabitants of all ages and 0.18 per 1,000 children. The incidence rates of acute
      rheumatism among children and adolescents annually increased by 62%. This rise
      was solely due to the North-Caucasian region of the Russian Federation where the
      pediatric morbidity was 0.92%. The statistical findings are regarded as an
      alarming signal for the likelihood of acute rheumatic fever in the Russian
      Federation.

PMID- 9011276
TI  - [Surprises of streptococcal infection].

PMID- 9011278
TI  - [Medical ethic aspects and the present time].

PMID- 9011277
TI  - [New concepts of the mechanisms of immunopatholgies+ of Streptococcal etiology].
AB  - The paper summarizes the data on the role of immunoglobulin Fc-receptor proteins
      of group A streptococci as one of the leading agents of the pathogenicity that
      initiates severe poststreptococcal complications in the comprehensive
      immunological and morphological study of acute experimental glomerulonephritis.
      In addition to some pathogenic effects, evidence is presented for the capacity of
      IgG FcR-positive, rather than IgG FcR-negative, group A streptococci of inducing
      the synthesis of great quantities of anti-IgG which has been detected both in
      free circulation and as part of immune complexes. IgG FcR proteins induced the
      release of antiinflammatory cytokines (TNF-alpha in particular) and anti-IgG FcR
      proteins, concurrently with complement C, formed deposits in the structures of
      glomerules, resulting in destructive and degenerative changes. The morphological
      criteria for delayed hypersensitivity processes, which are typical of
      inflammatory reactions in immunopathologies are discussed in the paper.
      Immunomorphological and electron microscopic studies at early stages revealed
      signs of membrane-proliferative glomerulonephritis with a predominant response of
      podocytes and mesangial cells, which later progressed to developed fibrous,
      atrophic, glomerulonephritis. It should be stressed that IgG FcR proteins, such
      as A and G staphylococcal protein, group G streptococcal protein, unlike group A
      streptococcal protein with the similar function either failed to cause the
      described events or the latter occurred rarely or delayed. The findings provide
      evidence for the author's concept of the role of IgG Fc-receptors of group A
      streptococci in the development of complications of streptococcal etiology.

PMID- 9011279
TI  - [The pattern of predisposition to rheumatism].
AB  - The present study was based on the results of many-year studies of the Mongoloid
      populations the Tofalars (793 and 661 persons in 1973 and 1984, respectively),
      the Dolgans (n = 952) the Taimyr Yakuts (n = 452), the Todji Tuvins (n = 819) and
      a sample from 200 families of rheumatic patients in Moscow and Moscow Region. The
      interpopulation gene differentiation expressed through the generalized genetic
      distance (8) and the prevalence of rheumatism correlated (r = 0.63). There was
      also a correlation between the mean heterozygocity of the populations and the
      spread of rheumatism-the determination rate was 72%. Therefore, structural
      features of the populations have a definite impact on the prevalence of
      rheumatism and suggest that there is a genetic component in the determination of
      the disease. A segregative analysis indicated the adequacy of a multifactorial
      model for the majority of the studied populations, the contribution of a genetic
      component to the determination of varying susceptibility to rheumatism ranged
      from 71% in the population of the Tofalars to 100% in the populations of the
      Dolgans and the Tuvins. The results of testing the type of rheumatism inheritance
      using a SAL-2 model, the data of a regression analysis of susceptibility
      heritability and inbreedity of the populations, and a component resolution of
      phenotypic dispersion of susceptibility are indicative of its involvement, along
      with an additive component, in the determination of rheumatism. Clinical and
      genetic findings also suggest that there is a genetic heterogeneity both of
      rheumatism as a whole (verified +likely) and verified rheumatism (without and
      with cardiac diseases).

PMID- 9011280
TI  - [New potentialities of diagnosis and any primary prevention of rheumatic fever].

PMID- 9011281
TI  - [Activation of cellular immunity in acute rheumatic fever: clinical and
      pathogenetic significance].

PMID- 9011282
TI  - [Acute rheumatic fever and rheumatic heart disease: immunological studies].
AB  - A total of 216 patients with rheumatic fever and rheumatic heart from the
      Institute of Rheumatology and 126 patients with rheumatic heart diseases alone
      from the Center of Cardiosurgery were clinically and immunologically studied. The
      immunological study included the detection of b-hemolytic group A streptococcus,
      O-antistreptolysin, the measurement of C-reactive protein, immunoglobulins, C3,
      C4, Ciq-binding, anticardiolipin antibodies, etc. The findings indicated that the
      secondary penicillin prophylaxis prevents streptococcal pharyngitis and
      recurrence of acute rheumatic fever after 5 years. The high levels of Ciq-binding
      and anticardiolipin antibodies were directly proportional to the incidence rates
      of acute endocarditis and associated with the occurrence of venous and arterial
      thromboses.

PMID- 9011283
TI  - [Prospective epidemiological study of rheumatism in the Irkutsk Region].
AB  - The changes in the prevalence and primary incidence of rheumatism in the region
      were analyzed by the epidemiological surveys and notifications made in 1961 to
      1994. During this period, the primary incidence rates showed a 70-fold decrease,
      mainly due to those among females and children. The paper presents changes in the
      pattern of risk factors of rheumatism and defines the prevalence decrease rate of
      rheumatism in three follow-up periods. A comprehensive rehabilitation programme
      for rheumatic patients has been worked out.

PMID- 9011285
TI  - [Nesterov AI: a founder of medical science].

PMID- 9011284
TI  - [New trends in the study of the primary fibromyalgic syndrome].
AB  - The study of 1240 patients making complaints of osteomuscular pains showed that
      9.6% had clinical signs of primary fibromyalgia (PF). It provided new data on the
      clinical signs of PF, clinical and biochemical changes in this syndrome. The
      diagnostic and informative values of some signs and symptoms of PF are compared
      and new approaches to optimizing diagnostic criteria are outlined in the paper.
      The paper also gives new data on the combined therapy for PF, including the use
      of dimexide with nonhormonal antiinflammatory agents and sessions of acupuncture
      that promotes the normalization of dysfunctions. This may be useful for PF
      patients due to easy-to-use, available, and inexpensive treatment.

PMID- 9011286
TI  - [Nesterov's contribution to the development of Russian rheumatology].

PMID- 9011287
TI  - And God will fill the bullet holes with candy.

PMID- 9011288
TI  - Oh, for a little humanity.

PMID- 9011289
TI  - Don't leave a mess, call Triple S!

PMID- 9011290
TI  - Rowlandson's Death in the Nursery.

PMID- 9011291
TI  - Is this what we really want?

PMID- 9011292
TI  - Bears, academia, and anaesthesia: a controlled study.

PMID- 9011293
TI  - [Comparative analysis of the level of induction and inhibition of lipid
      peroxidation in cellular fractions of tissues from deep sea squid and mouse].

PMID- 9011294
TI  - [Hydroperoxy- and hydroxy-derivatives of free unsaturated fatty acids and
      phospholipids as modifiers of liposomal membrane structure].

PMID- 9011295
TI  - [Expression of corticoliberin (CRF) and somatostatin (SRIF) genes in accessory
      nonapeptidergic (magnocellular) neurosecretory nuclei in rat hypothalamus].

PMID- 9011296
TI  - [The effect of transcranial electrostimulation on the endogenous level of
      radioresistance of laboratory mice].

PMID- 9011298
TI  - [A simple and effective method of synthesis of chain-specific DNA probes].

PMID- 9011297
TI  - [Theoretical conformational NMR analysis of peptide RP342 of the immunogenic
      fragment of HIV-1 protein gp120].

PMID- 9011299
TI  - [Fractal self-organization in Escherichia coli populations: experimental study].

PMID- 9011301
TI  - [Monodispersed circular DNA in mammalian cells].

PMID- 9011300
TI  - [In vivo 31P-NMR spectroscopic study of changes in phosphate metabolism in
      Ehrlich carcinoma after treatment with hydralazine and hyperthermia].

PMID- 9011302
TI  - [Experimental study of the effect of physiologically active combinations on the
      stimulation of reparative osteogenesis].

PMID- 9011303
TI  - [The lack of isolating effect of NOR transposition during interspecies
      hybridization in mice].

PMID- 9011304
TI  - Proceedings of the 13th Symposium on Biomedical Applications of Chromatography
      and Electrophoresis. Prague, Czech Republic, September 4-7, 1995.

PMID- 9011305
TI  - Neuromuscular diseases: muscle.

PMID- 9011306
TI  - Isolation of microvascular endothelial cells using magnetic beads coated with
      anti-PECAM-1 antibodies.

PMID- 9011308
TI  - A tribute to Daniel Mazia (1912-96) - pioneer in the science of the mitotic
      apparatus.

PMID- 9011309
TI  - [Over-the-counter drug sales in pharmacies].
AB  - The present legally unregulated and ever-increasing assortment of over-the
      counter drugs sold in pharmacies has been analyzed. The assortment has been
      divided into 14 categories in which the number of sold package and their
      financial values was examined. The classic pharmaceutical assortment (registered
      mass-produced medicaments, requisites needed for health care, milk products,
      unregistered vitamin preparations and dietetic preparations) represent the
      decisive share in the financial value and number of packages of the over-the
      counter assortment in pharmacies. Further extension of the supply of pharmacies
      with nontraditional assortment does not appear to be suitable.

PMID- 9011307
TI  - Pharmacological characterization of desensitization in a human mGlu1 alpha
      expressing non-neuronal cell line co-transfected with a glutamate transporter.
AB  - 1. Stimulation of phosphoinositide hydrolysis by human mGlu1 alpha (HmGlu1 alpha)
      was examined in a non-neuronal cell line (AV12-664) co-expressing both HmGlu1
      alpha and a rat glutamate/aspartate transporter (GLAST). 2. Desensitization of
      HmGlu1 alpha could be elicited by inhibition of the GLAST transporter with the
      glutamate uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid (trans
      PDC). Maximal inhibition of HmGlu1 alpha-mediated phosphoinositide hydrolysis was
      induced upon 24 h pretreatment with trans-PDC. The concentration of glutamate in
      the extracellular medium also rose significantly in cells pretreated with trans
      PDC. Glutamate levels increased upon incubation with trans-PDC in a time
      dependent manner, with maximal glutamate levels attained after 24 h incubation
      with trans-PDC. 3. The time required for desensitization of HmGlu1 alpha by trans
      PDC was compared to the time course for desensitization elicited by the direct
      acting mGlu receptor agonists, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R
      ACPD) and (R,S)-3,5-dihydroxyphenylglycine (3,5-DHPG). Both direct-acting mGlu
      receptor agonists elicited desensitization of HmGlu1 alpha more rapidly than did
      trans-PDC, with maximal inhibition of agonist-induced phosphoinositide hydrolysis
      upon 12 h pretreatment. Agonist-induced desensitization could be fully reversed
      upon washout of agonist for 12 h. 4. Both mGlu receptor agonist- and trans-PDC
      induced desensitization of HmGlu1 alpha could be blocked by inclusion of (+)
      alpha-methyl-4-carboxyphenylglycine (MCPG), an mGlu receptor antagonist, in the
      pretreatment medium. 5. Agonist-stimulated phosphoinositide hydrolysis by HmGlu1
      alpha was found to parallel closely agonist-induced desensitization of HmGlu1
      alpha. Thus, the EC50 values for 1S,3R-ACPD- and 3,5-DHPG-stimulated
      phosphoinositide hydrolysis were similar to the EC50 values for eliciting
      desensitization of HmGlu1 alpha. 6. These studies demonstrate desensitization of
      recombinant human mGlu1 alpha receptor in a non-neuronal cell line in which the
      receptor can be regulated by direct activation or by manipulation of glutamate
      transporter activity. Desensitization of HmGlu1 alpha was found to be mediated by
      activation of the receptor since the mGlu receptor antagonist, MCPG, blocked both
      mGlu receptor agonist- and trans-PDC-induced desensitization of HmGlu1 alpha.
      Furthermore, agonist-induced desensitization of HmGlu1 alpha was found to
      parallel receptor-mediated stimulation of phosphoinositide hydrolysis.

PMID- 9011310
TI  - [alpha-Lipoic acid--a natural disulfide cofactor and antioxidant with
      anticarcinogenic effects].
AB  - The present survey summarizes the data about the structure, function and methods
      of investigation of the natural substance alpha-lipoic acid. This compound is an
      important growth factor of many microorganisms and at the same time a disulfide
      cofactor of dehydrogenases in oxidative phosphorylation. It is a physiological
      constituent of biological membranes, an efficient antioxidant and a scavenger of
      free radicals. Lipoic acid possesses anticarcinogenic and preventive effects
      which protect the calls from damage.

PMID- 9011311
TI  - [Royleanones in the roots of Salvia officinalis L. of domestic provenance and
      their antimicrobial activity].
AB  - The reported investigation of the constituents of the petroleum ether extract of
      the root of Salvia officinalis L. confirmed the presence of the following
      diterpene quinones: 12.hydroxy-8, 12-abietadiene-11, 14-dione (royleanone), 7
      alpha, 12-dihydroxy-8.12-abistadiene-11-14-dione (horminone) and 7 alpha-acetoxy
      12-hydroxy-8, 12-abietadiene-11,14-dione (7-O-acetylhorminone). The compounds
      were identified on the basic of the interpretation of results of spectral
      analysis. Isolated royleanones show antimicrobial activity against gram-positive
      bacteria (Staphylococcus aureus). A study of abietate diterpenoids in the root of
      Salvia officinalis L. of Slovak provenance has been performed for the first time.

PMID- 9011312
TI  - [Risk of adverse effects of drugs].
AB  - With regard to the demonstrated adverse effects of some vegetable drugs (Rubia
      tinctorum L., pyrrolizidine alkaloids), or serious suspicions of adverse effects
      (drugs containing hydroxyanthracene derivatives), the German Federal Health
      Authority (BGA) has taken the following measures: the drug Rubiae tinctorum radix
      and the preparations manufactured from it have been withdrawn from circulation,
      and in the drugs and preparations containing pyrrolizidine alkaloids and
      hydroxyanthracene derivatives the manner of use, dosing and information for the
      customer have been modified.

PMID- 9011313
TI  - [Piperazine analogs of aryloxyaminopropanols and a study of their effects on a
      model of the isolated guinea pig ileum].
AB  - Seven compounds belonging to the group of aryloxyaminopropanols with carbamate
      substitution of the aromatic ring and with derivatives of N-phenylpiperazine in
      the lipophilic part were prepared by a well-tried method. Selected drugs were
      pharmacologically evaluated by in vitro experiments. Aryloxyaminopropanol drugs
      confirmed their anti-calcium activity on the intestinal model. Significant anti
      calcium activity of agents IIIq and IIIb (pA2 = 6,83 +/- 1,47; 7, 12 +/- 1, 12
      was comparable to that found for the standards verapamil and flunarizine. These
      compounds were selected for in vivo experiments and evaluated for their effect on
      reperfusion-induced arrhythmias in anaesthetized rats. Results of these
      evaluations are given in the next article.

PMID- 9011314
TI  - [Preparation and pharmacologic characteristics of aryloxyaminopropanol
      derivatives with an assumed cardiovascular effect].
AB  - In an attempt to prepare drugs favourably influencing pathologically changed
      functions of the cardiovascular system, such as hypertension and ischemic cardiac
      disease, several chemical compounds were prepared in which benzhydrylpiperazine,
      alkyl, or substituted phenylpiperazine (fragments of the structures of calcium
      antagonists) were bound to the fundamental aryloxyamino-propanol skeleton (the
      carrier of beta-adrenolytic effect). The selected four compounds underwent basic
      pharmacological analysis. In experiments on the isolated spontaneously beating
      guinea-pig atria (beta 1), three compounds competitively inhibited the positively
      chronotropic effect of isoprenaline (pA2 = 6.40-7.24) and in experiments on the
      isolated tracheal guinea-pig muscle they antagonised the relaxation effect of
      isoprenaline beta 2, the pA2 values ranging from 5.90-7.58. It follows from the
      experiments on the isolated guinea-pig aorta contracted with 50 mM KCl that all
      compounds under study possess mild relaxation effects, the intensity of which is,
      however, lower than in the used standards flunarizine and verapamil.

PMID- 9011316
TI  - Reason and protest in the new urban public health movement: an observation on the
      sociological analysis of political discourse in the 'healthy city'.
AB  - The urban environment represents an important social and geographical focus for
      the international new urban public health movement in general and the World
      Health Organization's 'Healthy Cities' project in particular. Existing and new
      policies of relevance to urban health are however infused with notions of cause,
      effect and ideas of appropriate intervention that reflect highly malleable and
      more or less conscious expressions of rationality, self-interest and
      organizational purpose--factors central to sociological analysis of the political
      discourse and objectives associated with the new urban public health movement.
      This article begins to develop a research agenda in this respect through
      consideration of the 'language' of policy and reference to Habermas' idea of
      'communicative reason'. It is argued that case-study based research into the
      discourse of the new urban public health movement has to balance empirical
      accounts with analysis of the 'policy ontologies' that confront and underpin the
      mobilizations and has, secondly, to consider the 'communicative capacity and
      orientation' of such initiatives.

PMID- 9011315
TI  - [Synthesis of chemical drugs at the Pharmacy School of Brno 1945-60].
AB  - Besides the theoretical-systematic and control-analytic part, pharmaceutical
      chemistry included the synthesis of chemical drugs. These three disciplines were
      taught separately at the Faculty of Pharmacy. The discipline of synthesis of
      chemical drugs was constituted on the basis of the need to get the students of
      pharmacy acquainted with the chemical preparation of drugs and the methodology of
      research and to prepare specialists for pharmaceutical and chemical Industry.
      Intensive research in the field of drug synthesis contributed to its
      establishment. The data gained in this as well as world research served for the
      elaboration of a comprehensive conception of research of synthetic drugs, not
      hitherto completed and theoretically substantiated even in the world literature.

PMID- 9011317
TI  - Contemporary natural product chemistry. Dedicated to Professor Alan R. Battersby
      and Professor A. Ian Scott, recipients of the 1995 Tetrahedron Prize for
      Creativity in Organic Chemistry.

PMID- 9011318
TI  - [I. The biology of unconventional, transmissible agents or prions].

PMID- 9011319
TI  - [II. On current state of knowledge concerning bovine spongiform encephalopathy
      (mad cow disease)].

PMID- 9011320
TI  - Structural organization, chromosomal localization, expression and phylogenetic
      evaluation of mouse glutathione peroxidase encoding genes.
AB  - We have reported earlier the cloning and the chromosomal localization of 2 GPX
      encoding sequences expressed differentially within the mouse epididymis, gpx5 and
      gpx3. Here, we have mapped on the mouse chromosomes the third known murine GPX
      encoding gene, the cytosolic GPX or gpx1. We have compared the degree of identity
      of the 3 GPX proteins, the respective organization of the 3 corresponding single
      copy genes and, using degenerated oligonucleotides designed in highly conserved
      domains of the proteins, we have analyzed the expression of GPX-encoding genes in
      the mouse epididymis as well as in control tissues known to express GPX proteins
      (the liver for GPX1 and the kidney for GPX3). The 3 genes characterized to date
      were found expressed in each of the tissues tested but in a highly tissue
      restricted manner. Nucleotidic sequences comparisons were carried out on GPX
      encoding sequences from various species and were used to draw a dendrogram.
      Phylogenetic evaluation of the sequence information, as well as the chromosomal
      localizations, suggest that the GPX genes have evolved by duplication events
      followed by random insertions from a single ancestral gene.

PMID- 9011321
TI  - T-type calcium current is expressed in dedifferentiated adult rat ventricular
      cells in primary culture.
AB  - Ventricular myocytes isolated from the heart of adult rats were able do
      dedifferentiate within 7 days in primary culture using a medium containing 10%
      fetal calf serum. Calcium current was recorded in these cells by means of the
      whole cell patch clamp technique and compared to the calcium current obtained in
      freshly isolated myocytes and in non dedifferentiated cultured myocytes. In
      dedifferentiated cardiomyocytes, both T-type (ICa-T) and L-type (ICa-L) calcium
      current components were recorded while only L-type was observed in freshly
      isolated and in non dedifferentiated cultured myocytes. ICa-T was separated from
      ICa-L through its voltage dependence and its pharmacology. These results
      demonstrate that ICa-T which has been shown to be present at the neonatal stage
      but absent in adult ventricular cells can be reexpressed when adult cells were
      dedifferentiated in culture. Its possible involvement in development of cardiac
      cells and in electrophysiological properties leading to spontaneous activity is
      discussed.

PMID- 9011322
TI  - [Ethyl 4-methyloctanoate, major component of male pherome in Oryctes rhinoceros
      (L.) (Coleoptera, Dynastidae)].
AB  - Ethyl 4-methyloctanoate, which has already been described in Oryctes monoceros,
      has been identified, using extracts of effluvia collected from males, as being a
      major component of the male pheromone of O. rhinoceros. Field trials have been
      carried out in North Sumatra, Indonesia. Ethyl 4-methyloctanoate synthesized in
      the laboratory and released at 10 mg/d resulted in the capture of 6.8 insects per
      week per trap, whereas ethyl chrysanthemate (40 mg/d), an allelochemical compound
      once used as an attractant, only led to the capture of 0.3 insects, and the
      control none at all. The insects captured with the pheromone were 81% females,
      the majority being sexually mature. Discovery of this compound opens up new
      prospects for O. rhinoceros control.

PMID- 9011323
TI  - [C virus of Drosophila and dynamics of host population].
AB  - Drosophila melanogaster populations are naturally infected by the Drosophila C
      virus (DCV). Ingestion of this non-hereditary virus early in the life-cycle has a
      positive effect. Demographic parameters measured on DCV-free and DCV-infected
      populations of the same genotype enabled us to compute the population growth
      rates (multiplication rates) by means of matrix models. The DCV-infected sample
      had a larger growth rate both for low and high larval densities. Since it is not
      possible to experiment on a mixed population where DCV-free and DCV-infected
      individuals live together, a model combining competition and contamination was
      used. Simulations showed that coexistence of free and infected animals can occur.
      Such a result leads us to question the relation between population growth rate
      and fitness.

PMID- 9011324
TI  - Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative
      dementias obtained by high resolution proton magnetic resonance spectroscopy.
AB  - We have analyzed the cerebrospinal fluid (CSF) of 19 patients with multiple
      sclerosis (MS), 12 patients with degenerative dementia and 17 control patients
      using in vitro high resolution proton magnetic resonance spectroscopy (MRS) at
      400 MHz. The CSF metabolic profile is slightly modified in MS patients (increased
      lactate and fructose concentrations, decreased creatinine and phenylalanine
      concentrations) and is not correlated with the intensity of the intrathecal
      inflammation. Proton MRS of CSF does not differentiate relapsing-remitting MS and
      primary progressive MS. We have not detected any specific abnormal resonance in
      native or lyophilized CSF. The CSF metabolic profile of demented patients is much
      more altered (increased concentration of lactate, pyruvate, alanine, lysine,
      valine, leucine-isoleucine, tyrosine, glutamine) and is in agreement with a brain
      oxidative metabolism impairment as already described in Alzheimer's disease.
      Unassigned abnormal but non specific or constant resonances have been detected on
      MR spectra of demented patients. CSF inositol concentration is also increased in
      the CSF of patients with Alzheimer's disease. In vitro high resolution proton MRS
      of the CSF constitutes a new and original way to explore CSF for the differential
      and/or early diagnosis of dementias, as a complement to in vivo proton cerebral
      MRS.

PMID- 9011325
TI  - [Effects of dose rate on carcinogenesis after exposure of rats to low doses of
      neutron irradiation].
AB  - In this experiment we compared the efficiency of fission neutrons of californium
      252 at doses of 25 or 53 mGy in function of the dose rate. Two groups of male
      Sprague-Dawley rats were exposed at 100 or 420 days of age to fission neutrons
      with dose rates of 950 or 760 microGy/h for 26 or 33 h, and 2 other groups were
      irradiated over a year from 3 months to 15 months of age with dose rates of 3.58
      or 7.72 microGy/h. The 4 groups of animals were compared with a control group of
      501 rats. The reduction of effectiveness on cancer induction that we have
      previously shown at low dose rate with rats exposed to gamma rays or to alpha
      particles was not observed for low dose rate exposure with fission neutrons.

PMID- 9011326
TI  - [Reccurent abortions: unpublished syndrome suggesting the explanation of fetal
      death].
AB  - A report is given of 8 cases of recurrent "idiopathic" abortions sharing in
      common the following features, unreported so far: (1) high uterine arterial
      impedance; (2) decrease in endometrial thickness, in spite of normal hormonal and
      endometrial cycle at biopsy; (3) a history of previous curettages. Such a
      syndrome could be consistent with the existence of a narrow peripheral symphysis
      of the uterine cavity, unaffecting its shape at hysterography.

PMID- 9011327
TI  - Novel aspects of steroid hormone resistance. Symposium of the
      Sonderforschungsbereich 351. Abstracts.

PMID- 9011328
TI  - Abstracts from the 12th annual meeting of the section on calcium regulating
      hormones and bone metabolism of the German Endocrine Society. Heidelberg, October
      11-12, 1996.

PMID- 9011329
TI  - The role of leukotrienes in asthma and allergic rhinitis.
AB  - The recent elucidation of the inflammatory responses underlying asthma and
      allergic rhinitis has stimulated the development of new anti-asthma treatments,
      including numerous antileukotriene agents. These agents, which represent a new
      direction in targeted therapy, either antagonize the leukotriene receptor (e.g.
      zafirlukast) or block the synthesis of leukotrienes (e.g. zileuton). They have
      been used in preclinical and clinical studies involving normal subjects and
      patients with asthma or allergic rhinitis. These studies have generally supported
      the putative role of leukotrienes in the mechanisms of asthma and allergic
      rhinitis. With respect to asthma, the leukotrienes also appear to function as
      potent mediators of bronchoconstriction. The above cited results indicate that
      antileukotriene agents offer incremental improvements in airway caliber and may
      also attenuate the inflammatory response. Because they are orally administered,
      they should have the additional benefit of increasing patient compliance relative
      to other currently available treatments. In their current form, however, they may
      not be expected to replace the mainstays of current therapy but to act rather, as
      adjuvant therapy. Patients with relatively mild asthma may be able to achieve
      efficacy with an antileukotriene agent plus as needed beta-adrenergic agonists;
      patients with more significant disease might use antileukotriene agents as a
      supplement to another anti-inflammatory agent, such as cromolyn, nedocromil, or
      corticosteroids. Studies of asthma patients have confirmed the ability of
      antileukotriene agents to attenuate asthma-associated bronchoconstriction.
      Antileukotriene agents appear to significantly attenuate aspirin-, allergen-, and
      exercise-induced asthma, as well as the signs and symptoms of nocturnal and
      chronic asthma; they may have efficacy in other inflammation-associated disorders
      such as allergic rhinitis as well.

PMID- 9011330
TI  - [Advantages of laparatomy in the treatment of closed injuries of the abdomen and
      retroperitoneal space].

PMID- 9011331
TI  - [Use of low-intensity laser effects in the surgical treatment of patients with
      bleeding gastroduodenal ulcer].

PMID- 9011332
TI  - [Role of laparocentesis in emergency surgery].

PMID- 9011333
TI  - [Method of surgical treatment of adhesive disease and prevention of acute
      adhesive intestinal obstruction].

PMID- 9011334
TI  - [X-ray diagnosis of contusions of the lungs].

PMID- 9011335
TI  - [Bases and results of revascularization of the talus in fracture-dislocation].

PMID- 9011336
TI  - [Use of peritoneo-anal resection with levator sphincteroplasty in the treatment
      of cancer of the lower ampullary part of the rectum].

PMID- 9011337
TI  - [Restorative-reconstructive surgery in patients with colostomy done in colonic
      obstruction of tumorous origin].

PMID- 9011338
TI  - [Mechanisms of action and properties of the new antineoplastic agent
      polyplatillen and possibilities of its use in fields related to oncology].

PMID- 9011339
TI  - [75 years of the journal, Klinichna Khirurhiia].

PMID- 9011340
TI  - [Long term results of cryosurgical treatment of liver neoplasms].

PMID- 9011341
TI  - [Cancer of gastric stump after surgery of peptic ulcer].

PMID- 9011342
TI  - [Development of acute pancreatitis after gastrectomy in gastric cancer].

PMID- 9011343
TI  - [Organizational bases of providing medical aid in extreme conditions].

PMID- 9011344
TI  - [Causes and prognostic factors in etiology of local recurrence of rectal cancer].

PMID- 9011345
TI  - [Current principles of the surgical treatment of postoperative peritonitis].

PMID- 9011346
TI  - [Results of surgical and combined treatment of retroperitoneal non-organ
      neoformations].

PMID- 9011347
TI  - [Diet factors and risk of the development of colorectal cancer].

PMID- 9011348
TI  - [Severe multiple trauma in a victim during the 3d trimester of pregnancy with
      traumatic delivery into the abdominal cavity].

PMID- 9011349
TI  - [Surgical treatment of gastroduodenal hemorrhage of ulcer etiology at the central
      district hospital].

PMID- 9011350
TI  - [Rare cause of obturation intestinal obstruction].

PMID- 9011351
TI  - [Gallstone as the cause of the etiology of acute intestinal obstruction of the
      small intestine].

PMID- 9011352
TI  - [Phlegmonous-ulcerous diverticulitis complicated by perforation of acute gastric
      ulcer].

PMID- 9011353
TI  - [Closing of duodenal stump and crater of giant cancerous profusely bleeding
      ulcer].

PMID- 9011354
TI  - [Eventration of the greater omentum through laparoscopic wound].

PMID- 9011355
TI  - [Gangrenous appendicitis in a patient with internal strangulated hernia].

PMID- 9011356
TI  - [Visceral form of lymphogranulomatosis complicated by gastric hemorrhage and
      perforation].

PMID- 9011357
TI  - [Analysis of causes of prehospital mortality of trauma victims].

PMID- 9011358
TI  - Guideline development.

PMID- 9011359
TI  - Second generation NoF-NoC's.

PMID- 9011360
TI  - Dental plans remain tax free.

PMID- 9011361
TI  - The world of pre-paid dentistry.

PMID- 9011362
TI  - Heads up on hygiene.

PMID- 9011363
TI  - Intra-oral cameras--the next step.

PMID- 9011364
TI  - Periodontal manifestations of systemic diseases and their management.
AB  - Periodontal diseases result from the response of the host's periodontal tissue to
      the bacterial toxins present in dental plaque. Several systemic diseases have
      been shown to influence the course and severity of periodontal diseases by
      altering the inflammatory response of the host. This paper focuses on the
      manifestations and dental management of periodontal diseases when these types of
      systemic conditions, including diabetes mellitus, hormonal changes of pregnancy
      and puberty, HIV-associated infection, and various blood dyscrasias, are present.

PMID- 9011365
TI  - Topical steroid therapy in oral lichen planus: review of a novel delivery method
      in 24 patients.
AB  - Lichen planus is a chronic mucocutaneous disorder of unknown etiology. The
      natural progression of oral lichen planus (OLP) is long and can extend over a
      number of years. Although many patients with OLP remain asymptomatic, some
      experience periods of marked inflammation with breakdown of the lesions, and
      require treatment. Corticosteroids are the mainstay of treatment for oral
      lesions, but delivery to affected mucosal sites can be problematic. The purpose
      of this study was to retrospectively review the results of topical steroid
      therapy in a group of patients with OLP, using a novel delivery method. The
      records of 33 patients with biopsy-proven OLP were reviewed and the relevant
      clinical features were noted at minimum review intervals of one, six and 12
      months. Of this group, 24 patients had been treated using a standardized
      treatment protocol consisting of a corticosteroid ointment applied topically to
      mucosal lesions using cloth strips. Gingival lesions were treated using a steroid
      preparation in an adhesive paste. Nine patients remained asymptomatic and were
      not treated. In the treated group, 14/24 (58 per cent) of patients showed an
      improvement in symptoms by one month. The remainder showed no change or a
      worsening of their symptoms. Repetition of the treatment protocol resulted in
      improvement in all the non-responders, and by one year 23 of 24 (96 per cent) of
      the patients had experienced improvement or control of their symptoms. Long-term
      failure to control the symptoms in the single non-responding case was related to
      poor patient compliance. Results from this study show that a novel delivery
      method and treatment protocol for the application of topical steroids onto
      lesional mucosa is useful for the symptomatic control of oral lichen planus.

PMID- 9011366
TI  - Risk assessment in dentistry: health risks of dental amalgam revisited.
AB  - This paper reviews the basic methodology of risk assessment and describes the
      four steps involved, namely hazard identification, hazard evaluation, exposure
      evaluation, and risk estimation. The risk posed by the release of mercury vapor
      from dental amalgam restorations is used as an example to demonstrate the
      advantages and limitations of this process.

PMID- 9011367
TI  - Ontario dentists' knowledge and beliefs about selected aspects of diagnosis,
      prevention and restorative dentistry.
AB  - Based on the responses of 1,276 general dental practitioners in Ontario to a mail
      questionnaire, variations in certain aspects of the dentists' diagnostic,
      preventive and restorative knowledge and beliefs are examined. Despite recent
      practice recommendations and guidelines indicating that patient need and service
      selectivity, rather than traditional, routine prescriptions, should be the
      guiding principle of practice, many dentists seem to follow tradition in defining
      optimal intervals for dental examinations and prophylaxes, bitewing radiographs
      and topical fluoride applications. Although the respondents' knowledge and
      beliefs were correct and consistent with current evidence in many areas, some
      large deficiencies were identified. These include: a lack of awareness that
      professional prophylaxis prior to topical fluoride application is usually
      unnecessary and that sealant applications to certain teeth are not cost
      effective; an over-estimation of the speed at which dental caries progress
      through the enamel; and, despite good knowledge about the opportunities for the
      remineralization of enamel lesions with fluorides, a tendency to restore enamel
      caries. In some instances, practitioner beliefs were shown to influence practice.
      For example, dentists who knew about the slow progression of approximal surface
      caries also reported more often that bitewing intervals should be longer, and
      that the placement of a restoration should be delayed until the caries penetrates
      the dentin. Similarly, correct knowledge about sealant effectiveness was
      positively associated with high sealant use. If dentists are to be expected to
      understand and follow emerging diagnostic, preventive and restorative practice
      recommendations and guidelines, continuing education is required to correct and
      update some of their knowledge and beliefs, as displayed in the responses to this
      questionnaire.

PMID- 9011368
TI  - [Subgingival irrigation: a heresy?].
AB  - Bacteria are the principal causal factor for gingivitis and adult periodontitis.
      This article is a review of the pertinent literature regarding subgingival
      irrigation with antimicrobial agents. Furthermore, the clinical significance of
      this technique is evaluated. In order for the antimicrobial agent to reach the
      base of the periodontal pocket, the canula must be placed at least 3.0 mm
      subgingivally. Subgingival irrigation offers no added antimicrobial effect over
      root scaling alone, but may extend the therapeutic effect of scaling. The effect
      of subgingival irrigation is none the less temporary. Subgingival irrigation must
      be regarded as an alternative treatment for gingivitis and adult periodontitis
      when root scaling alone is not sufficient.

PMID- 9011369
TI  - [Scientific Commission for the Study of Social Inequities of Health in Spain].

PMID- 9011370
TI  - [Social inequities of health in Spain. Report of the Scientific Commission for
      the Study of Social Inequities in Health in Spain].
AB  - In 1993 the Ministry of Health of the Spanish Government appointed a Scientific
      Commission to analyze social inequalities in health in Spain, as well as to make
      recommendations for improving Spanish health, through the practical
      implementation of public policies to reduce existing inequalities. The present
      report is the result of the work carried out by the said Commission. It has the
      following aims: first, to present a general introduction to the topic of social
      inequalities in health; second, to offer a global vision of the topic in Spain
      based upon the editing of available information: finally, to encourage the need
      for an in-depth analysis of the study and the reduction in social inequalities in
      health in the scientific and social fields, offering illustrative examples. The
      first chapter points out the importance of the topic, and Spain is located in the
      international historical and geographical context. The second chapter presents
      the most important concepts regarding the definition and measurement of health
      and inequality. The third and fourth chapters review various international and
      national studies of particular importance, and the Spanish case includes the
      current limitations to research. The fifth chapter presents two original
      investigations on the four perspectives of social inequalities in health in
      Spain: death rate, noticeable health, conducts related to health and the use and
      access to health services. Chapter six comments on some examples of policies
      aimed at reducing inequalities in health. Finally, the seventh chapter summarises
      the main conclusions of the report and makes some recommendations both for the
      improvement of current information systems as well as for obtaining the main
      conclusions for the health policies. Amongst the report's main conclusions the
      following may be pointed out: 1) an ecological study on the social inequalities
      in the death rate of small areas between 1990-1992 has revealed the existence of
      inequalities at a small area level. Autonomous Communities and regions.
      Inequality is confirmed between North-Northwestern Spain (with a high level) and
      South-Southwestern Spain (with a low level). Likewise, a positive relationship
      may be observed between various social indicators and the death rate; 2) the
      analysis of health surveys for 1987 and 1993 according to social class has
      revealed the existence of inequalities in health. Thus, in most of the health
      variables studied regarding the state of health-the conducts related to health or
      health services-the most disadvantaged social classes present greater health
      problems; 3) the political social and health experiences carried out in the
      Basque Country and Barcelona respectively, aimed at improving living standards,
      social welfare and the health of the most vulnerable sectors of the population
      have been positive and should be expanded and studied in depth; 4) the study and
      decrease of social inequalities in health by putting into practice social and
      health public policies should be a main objective of all political and social
      forces.

PMID- 9011371
TI  - Synthesis of sialyl Le(x) ganglioside analogues sulfated at C-6 of either the
      galactose or N-acetylglucosamine residues, and at both of the galactose and N
      acetylglucosamine residues: probes for clarifying the real carbohydrate ligand of
      L-selectin.

PMID- 9011372
TI  - Oligosaccharides related to xyloglucan: synthesis and X-ray crystal structure of
      methyl 2-0-(alpha-L-fucopyranosyl)-beta-D-galactopyranoside.
AB  - The disaccharides methyl 2-O-(alpha-L-fucopyranosyl)-beta-D-galactopyranoside and
      methyl 2-O-(alpha-L-fucopyranosyl)-alpha-D-galactopyranoside have been
      synthesised using the assisted halide reaction of tri-O-benzyl-alpha-L
      fucopyranosyl bromide with methyl 3,4,6-tri-O-benzyl-beta-D-galactopyranoside and
      methyl 3,4,6-tri-O-benzyl-alpha-D-galactopyranoside to construct the interresidue
      glycosidic linkages. A crystal structure of methyl 2-O-(alpha-L-fucopyranosyl)
      beta-D-galactopyranoside was determined using Mo-K alpha X-ray data at 183 K. The
      space group is P1 (No. 1) with the unit cell containing two molecules of the
      disaccharide with unique conformations and a water molecule. The structure was
      refined to R = 0.0566 for 2969 reflections. The L-fucopyranosyl and D
      galactopyranosyl residues have the nominal 1C4 and 4C1 conformations,
      respectively. The interresidue torsion angles are comparable with those generated
      in a recent molecular modelling study.

PMID- 9011373
TI  - Structural studies of the exopolysaccharide produced by Lactobacillus paracasei
      34-1.
AB  - The exopolysaccharide produced by Lactobacillus paracasei 34-1 in a semi-defined
      medium was found to be a heteropolymer, composed of D-galactose, 2-acetamido-2
      deoxy-D-galactose, and sn-glycerol 3-phosphate in molar ratios of 3:1:1. By means
      of deglycerophosphorylation, methylation analysis, and 1D/2D NMR studies (1H,
      13C, and 31P) the polysaccharide was shown to consist of repeating units with the
      following structure: [formula: see text].

PMID- 9011374
TI  - Substrate specificity of native dTDP-D-glucose-4,6-dehydratase: chemo-enzymatic
      syntheses of artificial and naturally occurring deoxy sugars.
AB  - Incubation of dTDP-glucose with the enzyme dTDP-glucose-4,6-dehydratase [EC
      4.2.1.46] from wild type E. coli B yielded a mixture of 3- and 4-keto-6-deoxy
      sugars after work-up. Model experiments with chemically synthesized methyl 6
      deoxy-4-keto-glucoside (9) revealed that dTDP-6-deoxy-alpha-D-ribo-hexopyran-3
      ulose (3) is formed by keto-enol tautomerization during the isolation procedure
      from initially formed dTDP-6-deoxy-alpha-D-xylo-hexopyran-4-ulose (2). dTDP-3
      deoxyglucose (4) and dTDP-3-azido-3-deoxyglucose (6) were substrates and showed
      Michaelis-Menten kinetics (4: KM = 200 microM and V(max) = 130 mumol/h mg; 6: KM
      = 300 microM and V(max) = 90 mumol/h mg). In 100-mg-scale experiments, both non
      natural substrates gave the respective 6-deoxy-4-keto compounds, dTDP-3,6-dideoxy
      alpha-D-erythro-hexopyran-4-ulose (5) and dTDP-3-azido-3,6-dideoxy-alpha-D-xylo
      hexopyran-4-ulose++ + (7), in yields ranging from 24 to 40%.

PMID- 9011375
TI  - Carboxyl-reduced hyaluronan: preparation and enzymatic assay.

PMID- 9011376
TI  - Synthesis and antiviral activity of 3'-C-branched-3'-deoxy analogues of
      adenosine.
AB  - The synthesis of some 3'-C-branched-3'-deoxy adenine nucleosides is described.
      Starting from the known 3-deoxy-3-C-(hydroxymethyl)-1,2;5,6-di-O-isopropylidene
      alpha-D-allof uranose (1), a versatile glycosylating agent, namely 1,2-di-O
      acetyl-5-O-benzoyl-3-deoxy-3-C-(mesyloxymethyl)-beta-D-ri bofuranose (6), was
      prepared in three steps. Condensation of the latter with bis(trimethysilylated)
      N6-benzoyladenine in the presence of tin(IV) chloride gave the N9-beta-nucleoside
      7. Compound 7 was converted into (i) 9-[3-C-(azidomethyl)-3-deoxy-beta-D
      ribofuranosyl]adenine (10), (ii) 9-[3-C-(azidomethyl)-2,3-dideoxy-beta-D-glycero
      pent-2-enofuran osyl]adenine (14) and 9-[2-azido-3-C-(azidomethyl)-2,3-dideoxy
      beta-D-arabinofuranosyl]a denine (15), and (iii) 9-[3-deoxy-2-O,3-C-(methylene)
      beta-D-ribofuranosyl]adenine (16). None of the tested nucleosides showed marked
      cytostatic or antiviral activity in vitro.

PMID- 9011377
TI  - Structural studies of the acidic exopolysaccharide produced by a mucoid strain of
      Burkholderia cepacia, isolated from cystic fibrosis.
AB  - The acidic exopolysaccharide produced by a mucoid strain of Burkholderia cepacia
      isolated from a cystic fibrosis patient, was purified by cetyltrimethylammonium
      bromide precipitation and/or anion-exchange chromatography. Based on the sugar
      composition and permethylation analyses, supported by GLC-MS and NMR spectroscopy
      analyses, the repeating-unit of the polysaccharide was established as -->3)-beta
      D-Glcp-(1-->3)-[4,6-O-(1-carboxyethylidene)]-alpha-D-Gal p-(1-->.

PMID- 9011378
TI  - Structural studies of the exocellular polysaccharide from Sphingomonas
      paucimobilis strain I-886.
AB  - The exocellular polysaccharide from Sphingomonas paucimobilis strain I-886 has
      been studied using methylation analysis, Smith degradation, partial acid
      hydrolysis, NMR spectroscopy, and mass spectrometry as the principal methods. It
      is concluded that the repeating unit has the following structure: [formula: see
      text] The absolute configuration of the uronic acid was deduced from 1H NMR
      chemical shifts and is most likely D. Some preparations of the polysaccharide
      also contain phosphate and O-acyl groups which have not been identified or
      localised.

PMID- 9011379
TI  - The structures of arabinoxyloglucans produced by solanaceous plants.
AB  - Several structural features, most notably the presence of alpha-L-Araf-(1-->2)
      alpha-D-Xylp side chains, distinguish the arabinoxyloglucans (AXGs) produced by
      solanaceous plants from the xyloglucans produced by other dicotyledonous plants.
      However, previous studies did not establish the exact order of attachment of the
      various side chains along the backbone of these AXGs. Therefore, oligosaccharide
      subunits of the AXGs secreted by suspension-cultured tobacco and tomato cells
      were generated by treatment of the isolated AXGs with a fungal endo-beta-(1-->4)
      D-glucanase (EG). The oligosaccharides were reduced with sodium borohydride to
      the corresponding oligoglycosyl alditol derivatives and purified by a combination
      of gel-permeation chromatography, reversed-phase HPLC, and HPAE chromatography.
      The isolated oligoglycosyl alditols were chemically characterized by NMR
      spectroscopy, matrix-assisted laser-desorption/ionization time-of-flight mass
      spectrometry (MALDITOFMS), fast-atom bombardment mass spectrometry (FABMS),
      FABMS/MS, and glycosyl-linkage analysis. The results confirmed that the AXGs from
      these species are composed of a (1-->4)-linked beta-D-Glcp backbone substituted
      at O-6 with various side chains. Both tobacco and tomato AXG contain alpha-D-Xylp
      and alpha-L-Araf-(1-->2)-alpha-D-Xylp side chains. However, oligosaccharide
      fragments of tomato AXG were also shown to contain beta-D-Galp-(1-->2)-alpha-D
      Xylp and beta-Araf-(1-->3)-alpha-L-Araf-(1-->2)-alpha-D-Xylp side chains that are
      not present in the tobacco AXG. This is the first report of beta-Araf residues in
      a xyloglucan. The primary structures of 20 oligosaccharides generated by EG
      treatment of tobacco AXG were determined. The generation of such a large number
      of oligosaccharides is due in part to the presence of O-acetyl substituents at O
      6 of many of the backbone beta-D-Glcp residues of tobacco AXG. The presence of
      either an O-acetyl or a glycosidic substituent at O-6 of a beta-D-Glc p residue
      in the AXG backbone protects the glycosidic bond of this residue from cleavage by
      the EG. Removal of the O-acetyl substituents prior to EG-treatment of the AXG
      results in oligosacharide fragments that are smaller than those produced by EG
      treatment of the O-acetylated AXG. Therefore, analysis of the complex mixture of
      oligosaccharides obtained by EG treatment of native tobacco AXGs provides
      information regarding the distribution of AXG side chains that would be lost if
      the AXG is de-O-acetylated prior to EG-treatment. Furthermore, the large library
      of oligosaccharide fragments generated by this approach revealed additional
      correlations between the structural features of AXGs and diagnosis chemical shift
      effects in their 1H NMR spectra.

PMID- 9011380
TI  - Synthesis and characterization of a carbene-generating biotinylated N
      acetylglucosamine for photoaffinity labeling of beta-(1-->4)
      galactosyltransferase.
AB  - A photoreactive N-acetylglucosamine derivative, N-[2-[2-[2-(2
      biotinylaminoethoxy)-ethoxy]ethoxy]-4-[3-(trifluo rom ethyl)-3-H-diazirin-3
      yl]benzoyl]-N4-[2-(acetylamino)-deoxy-beta-D -glucopyranosyl]-L-aspartamide
      (BDGA), was synthesized as a carbene-generating biotinylated probe for UDP
      galactose:N-acetylglucosamine beta-(1-->4)-galactosyltransferase (GalT). The
      photoaffinity labeling experiments of bovine GalT with BDGA under various
      condition were examined based on the quantitative chemiluminescent detection of
      the biotinyl residue which was photochemically introduced into in GalT protein. A
      progressive decrease in the yield of specific photolabeling was observed upon
      lowering the incubation temperature from 37 degrees C to 20 degrees C or 4 degree
      C. The amount of photoincorporation was also decreased when UMP was not included
      in the incubation mixture. Using a crude protein mixture of recombinant human
      GalT, a band corresponding to the glutathione S-transferase fusion GalT protein
      was also specifically visualized. Furthermore, combine use of BDGA photolabeling
      with an immobilized avidin was found to be effective for the selective retrieval
      of photolabeled GalT from a reaction mixture containing a large amount of
      unlabeled GalT protein. The results obtained clearly demonstrate that the
      covalent biotinylation using the carbene-generating photoaffinity reagent BDGA
      would be useful for the analysis of acceptor substrate binding sites within the
      GalT protein.

PMID- 9011383
TI  - The 1996 Nobel Prize to Rolf Zinkernagel and Peter Doherty.

PMID- 9011381
TI  - Rapid increase of resistance to erythromycin and clindamycin in Streptococcus
      pyogenes in Italy, 1993-1995. The Italian Surveillance Group for Antimicrobial
      Resistance.
AB  - A survey of antibiotic resistance in Streptococcus pyogenes in Italy showed a
      sharp increase in erythromycin resistance. In 1993, the incidence of erythromycin
      resistant strains was on average 5.1%, with marked variations by geographic area.
      Two years later, the incidence of these strains had registered a 1.5- to roughly
      20-fold increase, with a mean value of 25.9%, exceeding 40% in three centers out
      of 13 and 30% in another four. For all the strains studied, normal levels of
      susceptibility to penicillin were reported.

PMID- 9011384
TI  - The NADPH-diaphorase-containing system in the brain of the budgerigar
      (Melopsittacus undulatus).
AB  - In the present investigation we studied the presence and distribution of
      histochemically detected neuronal NADPH-diaphorase (ND) in the brain of the
      budgerigar, Melopsittacus undulatus. Positive neurons are widely distributed
      throughout the central nervous system. ND-containing neurons are present in the
      telencephalon and the paleostriatal-parolfactory lobe complex. Positive cells
      were observed also in the neostriatum, including the main auditory area (field
      L), in several nuclei of the archistriatum and in the hyperstriatum (accessory,
      dorsal, and ventral). In the diencephalon, positive neurons were present both in
      the lateral hypothalamic and periventricular areas, and in a segregate area at
      the confluence of the anterior commissure and the lateral prosencephalic bundle.
      A group of positive perikarya was located lateral to the dorsal part of the IIIrd
      ventricle, and continued laterally into the thalamus. Weakly stained neurons were
      observed in the thalamic dorsomedial posterior nucleus. In the mesencephalon, ND
      containing neurons were scattered in the reticular formation (pars lateralis and
      pars medialis) and in the optic tecta. A large population of positive neurons was
      observed in the substantia nigra, the ventral area of Tsai and the nucleus
      interpeduncularis. Positive neurons extended through the tegmental nuclei to the
      locus coeruleus. In the cerebellum, the granular neurons were weakly stained and
      the internal cerebellar nuclei were surrounded by a wide network of positive
      fibers. In the medulla the number of positive cells was highly reduced, but
      stained neurons were observed in the cochlear as well in the vestibular nuclei.
      The data here presented suggest that the distribution of ND-containing neurons in
      the brain of the budgerigar is different from those of the chicken and quail. The
      locations of positive neurons suggest also a possible involvement in sound
      perception and production pathways, and visual perception.

PMID- 9011385
TI  - Topography and immunocytochemical characterization of nerve fibers in the
      leptomeningeal compartments of the rat. A light- and electron-microscopical
      study.
AB  - The localization of peptidergic, catecholaminergic, and nitroxidergic nerve
      fibers in the ventral leptomeningeal connective tissue compartment was studied in
      whole-mount preparations and serial semithin and ultrathin sections. For
      immunocytochemistry, whole-mount preparations of the leptomeninges and ventral
      brain slices with the meninges were incubated as free-floating specimens with
      primary antibodies against protein gene product 9.5 (PGP 9.5), substance P (SP),
      calcitonin gene-related peptide (CGRP), dopamine beta-hydroxylase (DbetaH),
      vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and nitric oxide
      synthase (NOS) using the avidin-biotin-peroxidase method. Based on the regional
      differences of the connective tissue organization, the leptomeninx is subdivided
      into the pial, trabecular, and adventitial leptomeninx. The antibody PGP 9.5
      stains all unmyelinated nerve fibers in the leptomeninx. Although the highest
      density of nerve fibers occurs in the adventitial leptomeninx, nerve fibers, and
      terminals are additionally present in the trabecular and pial leptomeninx. DbetaH
      , NPY-, VIP- and NOS-immunoreactive (IR) nerve fibers occur exclusively in the
      adventitial leptomeninx forming neuromuscular junctions. CGRP- and SP-IR nerve
      fibers are localized in all three leptomeningeal compartments where they
      terminate close to the subarachnoid space (type 1) or within the connective
      tissue (type 2). Due to their morphological and immunocytochemical
      characterization a possible chemo-, mechano- or nociceptive function is discussed
      in the context of pathophysiological aspects.

PMID- 9011387
TI  - Projections and neurochemical coding of myenteric neurons innervating the mucosa
      of the guinea pig proximal colon.
AB  - Myenteric neurons projecting to the mucosa of the guinea pig proximal colon were
      identified using the combination of a neuronal tracing method and
      immunohistochemical techniques. The tracer DiI (1, 1'didodecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate) was applied onto the mucosa of a
      specimen of proximal colon which was then placed in organotypic culture to allow
      retrograde transport of the dye. After culture, the myenteric plexus was stained
      with antisera raised against choline acetyltransferase (ChAT) and calbindin
      (Calb). Of the myenteric neurons labeled with DiI, 99% had smooth cell bodies
      with Dogiel Type II morphology. Of these neurons, 70% projected in the
      longitudinal direction and the majority of them (65%) were located anally from
      the DiI application site, i.e., had ascending projections. Ascending neurons
      projected over significantly shorter distances than descending ones (3.1+/-0.5 mm
      vs. 4.6+/-1.2 mm, respectively; P<0.01). Of the labeled myenteric neurons, 98%
      were ChAT immunoreactive. Of these neurons, 78% were also immunoreactive for Calb
      and were preferentially ascending neurons. ChAT-immunoreactive but Calb-negative
      neurons did not have preferential projection. This study revealed the presence of
      two populations of myenteric neurons projecting to the mucosa of the guinea pig
      proximal colon. Morphological characteristics and neurochemical coding were
      suggestive for a putative sensory function for these neurons.

PMID- 9011386
TI  - Spatial relationships of enteric nerve fibers to vagal motor terminals and the
      sarcolemma in motor endplates of the rat esophagus: a confocal laser scanning and
      electron-microscopic study.
AB  - Enteric co-innervation of motor endplates in the rat esophagus was studied with
      confocal laser scanning and electron microscopy. Enteric fibers were demonstrated
      with immunocytochemistry for nitric oxide synthase, vasoactive intestinal peptide
      or NADPH-diaphorase histochemistry. Vagal motor terminals were identified with
      calcitonin gene-related peptide (CGRP) immunocytochemistry. Teloglia was stained
      with immuno- cytochemistry for S100, and TRITC-tagged alpha-bungarotoxin was used
      to delineate endplate areas in immmunofluorescence preparations. Both confocal
      imaging and electron microscopy revealed intimate relationships between enteric
      and vagal terminals on the one hand, and enteric terminals and the sarcolemma on
      the other. In addition, electron microscopy could point out direct apposition of
      a significant proportion of enteric varicosities to vagal motor terminals without
      intervening teloglial processes. These morphological data are compatible with pre
      and postsynaptic modulatory effects of enteric neurons on vagal neuromuscular
      transmission in striated esophageal muscle.

PMID- 9011382
TI  - A global theme issue: bibliography of references.

PMID- 9011388
TI  - Morphological classification of NADPHd-positive and -negative myenteric neurons
      in the porcine small intestine.
AB  - In this study, the neuronal nitric oxide synthase (nNOS)-related NADPHd reaction
      was combined with a silver impregnation method to visualize the morphology of
      nitrergic and non-nitrergic enteric neurons in the pig. Based on colour
      combination, NADPHd-positive and impregnated, NADPHd-negative but impregnated and
      NADPHd-positive but non-impregnated groups of nerve cells could be distinguished
      in whole-mounts of the small intestine. Neurons of the first two groups could be
      classified morphologically. NADPHd-positive and impregnated cells showed type III
      and type VI morphology, the first being located preferably in the upper, the
      latter in the lower small intestine. Both project largely in an aboral direction.
      NADPHd-negative but silver impregnated are the orally projecting type I, the
      adendritic, mostly circumferentially projecting type II, the vertically - to the
      submucous plexuses - projecting type IV and the aborally projecting type V
      neurons. Given that NADPHd and nNOS are identical, we conclude that type III and
      type VI neurons are nitrergic and type I, II, IV and V neurons are non-nitrergic.
      A considerable number of mostly smaller NADPHd-positive but non-impregnated
      neurons could not be classified.

PMID- 9011389
TI  - Oligodendrocytes isolated from adult pig brain synthesise and release
      prostaglandins.
AB  - The synthesis and release of prostaglandins have been studied in oligodendrocytes
      isolated from adult pig brain. Radioactively labelled arachidonic acid and di
      homo-y-linoleic acid were offered as precursors and their incorporation into
      individual phospholipids followed. Most of the labelling was incorporated into
      phosphatidylinositol, which may serve as a major source for precursors of the
      eicosanoid biosynthesis. Oligodendrocytes are capable of synthesising and
      releasing prostaglandins of the E- and F-series in vitro. Cyclooxygenase, the
      principal enzyme for prostaglandin synthesis, was localised in oligodendrocytes
      immunocytochemically by using a double-labelling technique which identified the
      oligodendrocytes via anti-galactosylcerebroside. The production and release of
      oligodendroglial prostaglandins indicate that oligodendrocytes themselves can
      modulate immune-mediated processes in the white matter of the central nervous
      system. Furthermore, prostaglandins may also play a role during remyelination.

PMID- 9011390
TI  - Variation of immunocytochemical expression of transforming growth factor (TGF)
      beta in hepatocytes in culture and liver slices.
AB  - Transforming growth factor beta (TGF-beta) is a major member of a cytokine family
      with pluripotent biological activity. In the liver, TGF-beta has
      pathophysiological significance with respect to hepatic fibrogenesis, regulation
      of liver cell growth, tumor development, and induction of hepatocellular
      apoptosis. We show that the expression of immunocytochemically detectable TGF
      beta in cultured hepatocytes is strongly dependent on culture conditions and
      cellular microenvironment. Hepatocytes in situ and freshly isolated cells are TGF
      beta negative. In contrast, hepatocytes in incubated liver slices are stained
      with a patch-like pattern, whereas parenchymal cells cultured as a monolayer
      exhibit strong diffuse positive immunostaining for TGF-beta within 2 h after
      seeding. The intensity of immunocytochemical staining is dependent on culture
      substrata, major expression being observed in cells maintained on glass or
      plastic surfaces. When collagen type-I and type-IV, or EHS-matrix are used as
      substrata, TGF-beta is absent or only weakly immunocytochemically apparent in
      cultured hepatocytes, irrespective of the culture medium used. The positive
      immunocytochemical expression of TGF-beta in hepatocytes arises neither by
      transcriptional and translational pathways nor by disturbed intracellular calcium
      homeostasis. However, calcium-dependent proteinases, such as calpain-I and -II,
      might be involved in the immunochemical presentation of intracellular TGF-beta,
      because respective calpain inhibitors strongly reduce the appearance of TGF-beta
      in cultured parenchymal liver cells. Thus, hepatocytes are a major cellular
      source of (latent) TGF-beta in liver, as becomes evident during culture.

PMID- 9011391
TI  - Gene expression of aphrodisin in female hamster genital tract segments.
AB  - Aphrodisin is a glycoprotein originally isolated from hamster vaginal discharge
      which was demonstrated to be involved in pheromonal effects on male hamsters. In
      the present study, we investigated the localization of aphrodisin-synthesizing
      and -storing cells in the entire genital tract of the female golden hamster using
      immunohistochemical and molecular biological methods. By use of
      immunohistochemical methods, significant aphrodisin immunoreactivity was detected
      within the cervical glandular tissue. Western blot analysis revealed high
      concentration of aphrodisin in vaginal discharge and in tissue extracts from the
      vagina and the cervix uteri. According to intracellular localization of
      aphrodisin, this protein is confined to cytoplasm of the immunoreactive cells.
      Immunoreactivity was also detected extracellularly on the surface of the anterior
      vaginal pluristratified epithelium. Semiquantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis showed an extremely high level of
      aphrodisin gene expression in the vagina and in the lower part of the uterus
      comprising the cervix. However, aphrodisin gene expression was also demonstrated
      in the middle part of the uterus and at a low level even in the ovaries. No
      aphrodisin gene expression was detectable in the upper part of the uterus and the
      uterine horns. In situ hybridization confirmed that the maximum expression of the
      aphrodisin gene is encountered in glandular cells of the cervix uteri. These
      results indicate that within the female hamster genital tract aphrodisin is
      predominantly synthesized throughout the vagina and cervical uterus. The protein
      is then secreted into the vaginal lumen. It is under discussion whether the
      accumulation of aphrodisin in the vaginal discharge facilitates the transfer of
      pheromone of low molecular weight to the male hamster's vomeronasal organ during
      investigatory behavior.

PMID- 9011393
TI  - Establishment of a human endometrial cell culture system and characterization of
      its polarized hormone responsive epithelial cells.
AB  - Uterine epithelial cells from normal human endometrium were cultured as a primary
      cell culture in a dual-chambered system. The epithelial cells were isolated from
      endometrial tissue of the proliferative phase obtained by hysterectomy. The
      epithelial cells were seeded on Millicell CM filters coated with the
      extracellular matrix Matrigel. Depending on the culture conditions, the
      epithelial cells formed a polarized cell monolayer on Matrigel or gland-like
      structures in Matrigel. The epithelial cell polarity was maintained during
      culture, which could be proved by electron microscopy. The progesterone and
      estrogen receptors as typical marker molecules for physiologically intact
      endometrial epithelial cells could be detected immunohistochemically as well as
      by RT-PCR in vitro and were down-regulated by medroxyprogesterone acetate (MPA)
      used as progesterone analogue. As this cell culture system exhibits morphological
      and immunohistochemical characteristics, typical for the in vivo situation, and
      since it can be modulated by hormone treatment under the in vitro conditions
      described, it represents a valuable tool for investigating processes that are
      essential for endometrial differentiation and reproductive functions.

PMID- 9011392
TI  - Nitric oxide/cGMP pathway components in the Leydig cells of the human testis.
AB  - In this study we sought to determine whether the main components of the nitric
      oxide (NO) pathway are localized within the Leydig cells of the human testis and
      whether the soluble guanylyl cyclase (sGC), the enzyme that accounts for NO
      effects, is functionally active in these cells. Using an amplified
      immunocytochemical technique, immunoreactivity for nitric oxide synthase (NOS-I),
      sGC and cyclic guanosine monophosphate (cGMP) was detected within the cytoplasm
      of human Leydig cells. Distinct differences in staining intensity were found
      between individual Leydig cells, between cell groups and between Leydig cells of
      different patients. By means of a specific cGMP-RIA, a concentration-dependent
      increase in the quantity of cGMP was measured in primary cultures of human Leydig
      cells following exposure to the NO donor sodium nitroprusside. In addition, NOS-I
      immunoreactivity was seen in Sertoli cells, whereas cGMP and sGC immunoreactivity
      was found in Sertoli cells, some apically situated spermatids and residual bodies
      of seminiferous tubules. Dual-labelling studies and the staining of consecutive
      sections showed that there are several populations of Leydig cells in the human
      testis. Most cells were immunoreactive for NOS-I, sGC and cGMP, but smaller
      numbers of cells were unlabelled by any of the antibodies used, or labelled for
      NOS-I or cGMP alone, for sGC and cGMP, or for NOS-I and sGC. These results show
      that the Leydig cells possess both the enzyme by which NO is produced and the
      active enzyme which mediates the NO effects. There are different Leydig cell
      populations that probably reflect variations in their functional (steroidogenic)
      activity.

PMID- 9011394
TI  - Junctions between the sinus endothelial cells of rat spleen.
AB  - Junctions between the sinus endothelial cells of rat spleen were examined by
      electron microscopy, using both freeze-fracture and detergent-extraction
      techniques. Adherens and tight junctions were observed. Adherens junctions were
      the predominant junctional structures between endothelial cells and were located
      on basolateral and lateral surfaces. At the basolateral adherens junctions, actin
      filaments were associated with the junctional membranes and were continuous with
      the actin filaments in stress fibers. Cross-bridges were present in the
      interspaces of the adherens junctions and spacing of the bridges was fairly
      regular. A form of tight junction, the macula occludens, was also observed
      between the endothelial cells, but it was not observed at every cellular
      apposition. Electron-dense material, adjoining the cytoplasmic surfaces of
      membranes in the tight junctions, separated the junctional membranes from masses
      of thin filaments. At basolateral tight junctions, the actin filaments were
      continuous with those in the stress fibers. Based on these observations, the two
      intercellular junctions were considered to play important roles in sinus
      functions.

PMID- 9011395
TI  - Three-dimensional organization of the developing vasculature of the kidney.
AB  - Kidney function depends on a well-developed vascular system. Any impairment of
      the blood supply disturbs the integrity and function of the organ. The
      differentiation of renal vessels has been investigation for many years, but
      little is known about the relationship between nephrogenesis and vessel
      development. In the present work the spatial organization of the differentiating
      vessels was analyzed in precisely oriented tissue sections and in optical
      sections acquired by laser scan microscopy. Developing vessels as well as small
      capillaries were visualized with two endothelium-detecting antibodies. Small
      vessels running in parallel towards the organ capsule were detected in numerous
      cortico-medullary-oriented tissue sections. Cross-sections of the nephrogenic
      zone showed a regularly arranged network, which was composed of cells detected by
      both monoclonal antibodies. Parts of this network were localized in regions of
      the nephrogenic zone which have been assumed to be free of vessels or vessel-like
      structures for a long time. These results were confirmed by the laser-scan
      microscopic analysis of complete cortex explants. The extraordinarily regular
      arrangement of the endothelial network in the nephrogenic zone allowed us to
      reconstruct the developing vascular system. The results presented here underline
      the close relationship between nephrogenesis and vessel development.

PMID- 9011396
TI  - Opsin-like immunoreactivity in the circadian pacemaker neurons and photoreceptors
      of the eye of the opisthobranch mollusc Bulla gouldiana.
AB  - Circadian pacemaker cells in the eyes of the opisthobranch mollusc Bulla
      gouldiana generate a near 24-h rhythm in the frequency of optic nerve impulses.
      Previous electrophysiological studies suggest that these basal retinal neurons
      are intrinsically photosensitive and transduce light signals that shift the phase
      of their pacemaker mechanism. To test whether the pacemaker neurons contain opsin
      like proteins, several polyclonal antibodies that recognize opsins of vertebrate
      photoreceptors have been tested on histological sections of the eye and on the
      neurons in primary cell culture. The antibodies label both the pacemaker cells
      and the large distal photoreceptors that surround the lens. Immunoblot analyses
      of the proteins of the eye have identified a single band at 62+/-4 kDa. These
      opsin antibodies may label the photopigment used in the entrainment of the
      circadian pacemaker.

PMID- 9011397
TI  - Histamine-like immunoreactivity in the visual system and brain of an orthopteran
      and a hymenopteran insect.
AB  - The distribution of histamine-like immunoreactivity has been analyzed in the
      visual system and brain of the cricket Gryllus campestris and of the bee Apis
      mellifera by using an antiserum against histamine. Specific immunolabeling of the
      photoreceptors has been found in the compound eyes and ocelli of both examined
      species. Intense immunostaining can be also detected in the midbrain of these
      species. The axons of immunoreactive cells innervate almost every area in the
      protocerebrum. Most of the reactive neurons are typically wide-field neurons with
      bilateral ramifications that form dense arborizations. Numerous small buttons on
      the arborizations probably represent pre- and postsynaptic sites. The histamine
      like immunoreactive neurons are apparently connected to many postsynaptic
      neurons. In both bees and crickets, some regions of the nervous system such as
      the first two optic neuropils and the central body show the same labeling
      pattern, whereas the mushroom bodies exhibit no immunoreactivity. Nevertheless,
      several differences in the staining pattern can be seen: the glomeruli of the
      antennal lobe are invaded by histamine-like immunoreactive fibers in the bee but
      not in the cricket. Furthermore, an interneuron connects the second and third
      optic neuropil in the cricket, whereas no histamine-like immunoreactive
      interneuron is found in the second optic neuropil in the bee. In accord with the
      work of other authors on the distribution histamine in the insect nervous system,
      we suggest that histamine is not only a transmitter within the visual system, but
      also a transmitter or co-transmitter in the insect midbrain.

PMID- 9011398
TI  - Response of eosinophilic granule cells of gilthead seabream (Sparus aurata,
      Teleostei) to bacteria and bacterial products.
AB  - Eosinophilic granule cells in the gills and peritoneal exudate of gilthead
      seabream (Sparus aurata L.) are characterized by the presence of prominent
      eosinophilic granules in their cytoplasm and are here described for the first
      time. The oval granules of these cells contain an electron-dense inclusion
      surrounded by a less dense filamentous matrix and are peroxidase- and acid
      phosphatase-negative. Unlike other granulocytes of gilthead seabream,
      eosinophilic granule cells do not ingest bacteria in vivo. The intraperitoneal
      injection of extracellular products of Pasteurella piscicida induces mobilization
      of eosinophilic granule cells to the blood and other tissues and causes changes
      in their structure. Shortly after injection, the granules of eosinophilic granule
      cells become swollen and some fuse with the cell membrane. From 7 h post
      injection, many eosinophilic granule cells in the gills degenerate and are then
      phagocytosed by macrophages, which are especially abundant after 24 h. From 24 h
      to 72 h, eosinophilic granule cells from the gills contain abundant autolysosomes
      together with granules of a normal morphology.

PMID- 9011399
TI  - Transient expression of NMDA receptors during rearrangement of AMPA-receptor
      expressing fibers in the developing inner ear.
AB  - A major reorganization of afferent and efferent nerve terminals, concomitant to
      significant neuronal cell loss and pruning of superfluous fibers, takes place
      during the development of the organ of Corti, prior to the onset of hearing. We
      examined the spatio/temporal distribution of subtype-specific AMPA- and N-methyl
      d-aspartate (NMDA)-selective glutamate receptor proteins in postnatal inner ears
      from rats during this critical period. From the first postnatal day onwards,
      GluR2/3 receptor subtypes appeared in nerve endings of afferent fibers associated
      with inner and outer hair cells. During the following 2 weeks, GluR2/3 receptors
      were downregulated in exchange for GluR4 receptors. In parallel efferents
      projecting from the medial olivocochlear complex to the outer hair cells
      underwent synaptogenesis and efferents projecting from the lateral olivocochlear
      complex to the inner hair cells appeared to change contacts to the dendrites of
      afferents. Concomitant to these events, NMDA receptor subtypes NR1 and NR2A
      transiently appeared in hair cells as well as afferent and efferent fibers.
      Recently, we described a temporary expression of the neurotrophin receptor trkB
      in hair cells, coincident to the growth (GAP-43) and synaptogenesis
      (synaptophysin) of efferents. Here, we show that trkB was expressed together with
      NR1 receptors in hair cells in high spatio/temporal correlation with the
      rearrangement of afferents and efferents. Cochlea NMDA receptors may, therefore,
      be a part of the mechanism by which, in addition to neurotrophic activity, the
      mature phenotype of cochlea neurons is acquired through activity-dependent
      processes.

PMID- 9011400
TI  - Absence of the myelin-associated glycoprotein (MAG) and the neural cell adhesion
      molecule (N-CAM) interferes with the maintenance, but not with the formation of
      peripheral myelin.
AB  - We have previously shown that mice deficient in the gene for the myelin
      associated glycoprotein (MAG) develop normal myelin in the peripheral nerves, but
      show axon and myelin degeneration at eight months of age, suggesting that MAG is
      involved in the maintenance of axon-Schwann cell integrity. The search for
      molecules that might replace MAG during myelination revealed an overexpression of
      the neural cell adhesion molecule (N-CAM) at those aspects where MAG is
      detectable in wild type mice. To test whether N-CAM might compensate for MAG
      during myelination in MAG-deficient mice, double mutants deficient in both MAG
      and N-CAM (MAG-/N-CAM- mice) were generated by cross-breeding the single mutants.
      Whereas alterations of myelin development were not detectable in either of the
      single or double mutants, degeneration of myelin and axons occurred approximately
      4 weeks earlier in MAG-/N-CAM- than in MAG- mutants. Furthermore, at 8 weeks of
      age, single fiber preparation and electron microscopy revealed that the number of
      profiles indicative of degeneration was substantially increased in MAG-/N-CAM-
      mutants when compared to MAG- mice. These data suggest that in MAG-deficient mice
      N-CAM does not compensate for MAG in myelin formation but partially substitutes
      for it in the maintenance of axon-myelin integrity.

PMID- 9011401
TI  - Structural plasticity of optic synapses in the rat suprachiasmatic nucleus:
      adaptation to long-term influence of light and darkness.
AB  - Synapses of optic afferents (optic synapses) in the suprachiasmatic nucleus of
      hooded rats were morphometrically evaluated after exposing the animals to 12 h,
      14 days, 2 months, and 8 months of constant light (light rats) and darkness (dark
      rats). Compared with dark rats, optic synapses from light rats have larger
      boutons with larger mitochondria, more clear vesicles, fewer dense-core vesicles
      and front-line vesicles, smaller presynaptic dense projections, a smaller amount
      of postsynaptic density material, a smaller relative number of Gray-type I
      (asymmetric) junctions, a greater relative number of Gray-type II (symmetric)
      junctions, as well as more and larger mitochondria in the postsynaptic dendrites.
      Junctions of optic synapses are mostly straight, but the small number of
      positively curved contacts are more flattened in light rats than in dark rats. An
      age-related increase in the size of presynaptic dense projections was also
      observed. There are no changes in the sizes of clear and dense-core vesicles, in
      the size of synaptic junctions and their numerical density in area, and in the
      unspecific contact area between pre- and postsynaptic elements. The changes in
      optic boutons are characteristic for activated and relatively disused synapses
      with a slow, tonic firing rate. It appears that (1) the amount of postsynaptic
      density material is proportional to the strength of Gray-type I synapses, and
      that (2) some excitatory optic synapses become inhibitory after long-term
      activity, whereas some inhibitory synapses turn into excitatory contacts after
      long-term disuse.

PMID- 9011402
TI  - Ontogenesis of the alpha2-adrenergic receptor system in the hypothalamo-limbic
      system of the Pekin duck.
AB  - The development of the central nervous alpha2-adrenergic system in the duck was
      studied by semiquantitative autoradiography at the ontogenetic stages embryonic
      days 20 (E20) and 27 (E27) and postnatal days 3 (P3) and 14 (P14) by using the
      monoradioiodinated alpha2-agonist clonidine ([125I]CLO) as radioligand. All
      structures endowed with alpha2-adrenoceptors in the adult animal were
      specifically labeled with [125I]CLO by E20. A detailed analysis of the binding
      capacity for [125I]CLO was performed for parts of several functional systems:
      hypothalamic structures (nucleus inferior hypothalami, nucleus magnocellularis
      preopticus, nucleus paraventricularis), limbic system (habenula, nucleus septalis
      lateralis, nucleus striae terminalis), circumventricular organs (organum pineale,
      organum subfornicale, plexus choroidei ventriculi tertii and ventriculi
      lateralis), visual system (hyperstriatum accessorium, nucleus reticularis
      superior, tectum opticum), and associative cortex (hyperstriatum ventrale).
      Except for the nucleus inferior hypothalami and the plexus choroideus ventriculi
      lateralis, all structures showed a perinatal (E27-P3) maximum of alpha2
      adrenoceptor-binding capacity with a subsequent decline to values of prehatching
      stages. This uniform expression pattern of alpha2-adrenoceptors indicates that
      the days around hatching are a critical period for the development of the
      adrenergic system in the brain of the duck.

PMID- 9011403
TI  - Sexual dimorphism of arg-vasotocin gene expressing neurons in the telencephalon
      and dorsal diencephalon of the domestic fowl. An immunocytochemical and in situ
      hybridization study.
AB  - A strong sex dimorphism in the distribution of immunoreactive arginine-vasotocin
      (AVT) and AVT mRNA was observed in telencephalic and dorsal diencephalic areas of
      the domestic fowl using immunocytochemistry and in situ hybridization. Two
      subgroups of immunoreactive parvocellular perikarya surrounded by dense plexus of
      immunoreactive fibres were found within the bed nucleus of the stria terminalis
      and the dorsal part of the diencephalic paraventricular region of males. No signs
      of immunoreactivity were observed within corresponding regions of the female
      brain. Instead, in females a few scattered weakly stained perikarya were observed
      rostrally to the level of the anterior commissure, juxtapositioned to the nucleus
      accumbens and the floor of the lateral ventricle. The distribution of AVT mRNA
      containing cell profiles fully confirmed the immunocytochemical findings. Osmotic
      stress induced by water deprivation for 48 h had no influence on the number of
      immunoreactive or AVT mRNA containing parvocellular cell bodies. However, it
      resulted in an increase of immunoreactive cell area in the bed nucleus of the
      stria terminalis and dorsal diencephalon of 5. 9 and 11.7%, respectively. We
      suggest that the sexually dimorphic vasotocinergic circuit may be involved in the
      co-ordination of behavioural and autonomic functions in response to environmental
      stress.

PMID- 9011404
TI  - Direct hypertonic stimulation of the rat supraoptic nucleus increases c-fos
      expressionin glial cells rather than magnocellular neurones.
AB  - We investigated whether hypertonicity acts directly on supraoptic neurones to
      activate c-fos expression. Hypertonic artificial cerebrospinal fluid was infused
      into the supraoptic nucleus (SON) via a microdialysis probe implanted 24 h
      previously. The rats were decapitated after 90 min for immunohistochemistry with
      a Fos protein antibody. Direct hypertonic stimulation increased Fos protein
      expression in glial cells, identified by glial fibrillary acidic protein
      immunoreactivity, but not in magnocellular neurones. Similarly, with in situ
      hybridisation c-fos mRNA expression was predominantly seen in glial cells. Fos
      expression in SON neurones was stimulated by systemic hypertonicity even with a
      microdialysis probe in the SON, and magnocellular neurones expressed Fos after
      direct microinjection of cholecystokinin-8S into the SON. Thus, while direct
      hypertonic stimulation of SON neurones activates secretion of vasopressin and
      oxytocin, the c-fos gene is not activated, unlike following systemic hypertonic
      stimulation. This indicates that excitation of neuronal electrical and secretory
      activity does not necessarily lead to activation of the c-fos gene. Activation of
      c-fos expression in glial cells by direct hypertonic stimulation may reflect
      their role in regulating brain extracellular fluid composition.

PMID- 9011405
TI  - Visual connections of the atypical diencephalic nucleus rostrolateralis in
      Pantodon buchholzi (Teleostei, Osteoglossomorpha).
AB  - Among the many thousands of teleost fish species, a diencephalic nucleus
      rostrolateralis (RL) has been identified in only six widely divergent species. In
      one of these, Pantodon buchholzi, its retina projects to both RL and the optic
      tectum, the latter in a visuotopic manner. The ventral part of the retina beneath
      a horizontal black-pigmented septum connects to the dorsomedial optic tectum and
      nucleus RL. The dorsal part of the retina connects to the lateroventral optic
      tectum and little, if at all, to RL. Using DiI tracing, the position of RL in the
      optic pathway of this fish has been directly demonstrated. Cells in the stratum
      periventriculare of the dorsomedial optic tectum contribute to the afferent input
      of RL (bilaterally); cells in the ventrolateral tectum do not. RL is also
      reciprocally connected with the torus longitudinalis and may project to three
      nuclei of the preglomerular complex. Ganglion cells in the retina that project to
      RL are sparsely distributed throughout the ventral hemiretina compared with
      ganglion cells that project to the optic tectum. Since this fish is an obligatory
      surface feeder, the neuroanatomical connectivity of nucleus RL in P. buchholzi
      suggests a role in the fish's visual identification of targets for feeding
      behavior.

PMID- 9011406
TI  - Ciguatera and the anesthesiologist.

PMID- 9011407
TI  - AHA conference proceedings. Summary of the scientific conference on the efficacy
      of hypocholesterolemic dietary interventions. American Heart Association.

PMID- 9011408
TI  - Electrical restitution in ventricular myocardium.

PMID- 9011409
TI  - Phenotypic Characterisation of NIDDM in the East and West. Proceedings of a
      symposium. Tokyo, Japan, November 1994.

PMID- 9011411
TI  - [Opening address of the President of the Professional Organization of German
      Internists, H. Weinholz, at the 102nd Meeting of the Professional Organization of
      German Internists, Wiesbaden, 14 April 1996].

PMID- 9011410
TI  - Information integration about object-object relationships by chimpanzees (Pan
      troglodytes).
AB  - Three experiments tested the ability to integrate information about object-object
      relationships in 2 chimpanzees. In Experiment 1, the subjects were trained to
      match 1 part of a 2-part object to its other part, match a tool to its assembled
      object, match a container to its tool, and match a tool to its container. In
      Experiment 2, the subjects were trained to match a picture of the sample. One
      subject learned this type of matching task and was then tested on whether she
      could choose the pictures of related items in Experiment 1. Although the subject
      was reinforced irrespective of her choices, she chose pictures of items related
      to the sample when there was no picture of the sample. Experiment 3 showed that
      the subject was able to match a picture of the item among related items. The
      results suggest that the subject might integrate information about relationships
      acquired in Experiment 1 and organize it to make networks of related items.

PMID- 9011412
TI  - [Ambulatory surgery, quo vadis].

PMID- 9011413
TI  - [BSG accepts point value decline in ambulatory surgery for 1993 and 1994.
      Decisions of the Federal Social Court 7 February 1996--6 RKa 61/94 and 42/95].

PMID- 9011414
TI  - [Malpractice risks in ambulatory surgery. Measures for decreasing and preventing
      the risk].

PMID- 9011415
TI  - [Distal radius fracture--where does the error begin?].

PMID- 9011416
TI  - [The limits of human professional capacity].

PMID- 9011417
TI  - [Combined pancreas/kidney transplantation as standard procedure in therapy of
      type I diabetic patients in renal failure].
AB  - Sinde the introduction of the bladder drainage technique, the number of pancreas
      transplants performed has now reached 1000/year worldwide. Most of these
      transplants have been performed in the United States. In contrast, the number of
      pancreas transplants performed in the Eurotransplant community has remained at a
      low level for several years. The results of a consecutive series of 20
      simultaneous pancreas/kidney grafts (SPK) performed between June 1994 and October
      1995 demonstrate that high graft function rates of 83.5% for pancreas and kidney
      grafts can be achieved. Therefore SPK can be recommended as a standard procedure
      for patients with insulin-dependent diabetes mellitus and end-stage renal disease
      in Germany, too.

PMID- 9011418
TI  - [Value of the CA 19-9 tumor marker in differential diagnosis of space-occupying
      lesions in the head of the pancreas].
AB  - In 96 patients (ductal pancreatic carcinoma, n = 34; periampullary carcinoma, n =
      43; chronic pancreatitis, n = 19) the role of CA 19-9 in the diagnosis of lesions
      of the head of the pancreas were evaluated. The sensitivity for ductal pancreatic
      carcinoma was 73.3%, for periampullary carcinoma 48.8%, and specificity was
      63.2%. Carcinoembryonic antigen was elevated only in every fifth patient. Even
      when combining the two tumor markers no increase in sensitivity could be
      observed. The low specificity of 63%, which decreased to 33% in the case of
      obstructive jaundice, does not allow adequate preoperative differentiation
      between cancer patients and those with chronic pancreatitis. In cases of
      postoperatively elevated CA 19-9 level the prognosis is worse than in patients
      with normal tumor markers.

PMID- 9011419
TI  - [Solid pseudopapillary tumors of the pancreas].
AB  - We report on three female patients with solid pseudopapillary tumors of the
      pancreas. The histogenetic origin of this entity is still unclear. The tumor,
      usually occurring in young women, forms large masses (up to 10 cm in diameter)
      before becoming symptomatic. Metastases have very rarely been reported. In
      contrast to other pancreatic tumors, the main pancreatic duct was displaced, but
      of normal caliber without stenosis, in all our patients. Despite the large size
      of the tumors, they were curatively resected in all three cases. Two of the
      tumors infiltrated the parenchyma or adipose tissue of the pancreas but did not
      spread into the lymph nodes or other organs. All of the patients are alive and
      without signs of tumor recurrence up to 8 years after surgical resection.

PMID- 9011420
TI  - [Splenectomy in osteomyelofibrosis. Indications and outcome].
AB  - Osteomyelofibrosis is a myeloproliferative disorder in which fibrosis and
      sclerosis finally lead to bone marrow obliteration. Liver and spleen compensate
      for bone marrow loss with extramedullary hematopoiesis. In some patients the
      resulting splenomegaly causes severe symptoms such as local compression,
      thrombocytopenia and hemolytic anemia. In such patients, splenectomy is the only
      promising treatment, although it represents a significant risk.

PMID- 9011421
TI  - [Reconstruction of scar hernias--intraoperative tensiometry for objective
      determination of procedure of choice].
AB  - The reappearance of incisional hernias after reconstruction depends on the size
      and tension of the hernia. An additional risk factor is the number of operations
      that have been performed before. There are two decisive factors that influence
      the rate of recurrence: the operation technique and the tension applied. To reach
      a functional reconstruction the incisional hernia must be closed and the
      abdominal wall must be joined together in an anatomical way. The technique used
      must be able to tolerate the tension which is necessary to close the abdominal
      wall. Application of arbitrary tension produces a high rate of recurrence,
      irrespective of the kind of reconstruction used. Through the intraoperative
      measurement of the tension applied one can match each hernia (according to size,
      value and tension) to the most suitable technique. Here the inlay/onlay technique
      tolerates the highest tension, up to 3.5 kp. With this method and a maximum
      tension of 3.5 kp we achieved a complete functional reconstruction in 65% of
      cases and our rate of recurrence amounted to 2.3%.

PMID- 9011422
TI  - [Preperitoneal mesh-plasty in incisional hernia repair. A comparative
      retrospective study of 272 operated incisional hernias].
AB  - In a retrospective study on 245 patients we evaluated the results of 272
      incisional hernia repairs in the Department Surgery of the University Hospital
      Aachen. The group consisted of 58% male and 42% female patients with a mean age
      of 61.1 years and 111 primary and 161 recurrent incisional hernias. Conventional
      techniques (simple closure, Mayo) and alloplastic repairs were performed in 69.9
      and 30.1%, respectively. During the last 4 years we predominantly used the
      preperitoneal mesh repair with polypropylene mesh (Marlex). The results of 87% of
      our group of patients were evaluated by questionnaire and information from the
      family physicians (mean follow-up period 64 months). The patients who underwent
      preperitoneal mesh repair were examined clinically and with ultrasound. In
      comparison to the results of conventional hernia repair, early complications
      (seroma, hematoma) were higher. The recurrence rate, however, was significantly
      lower in this group with mesh repair (6.8%) than in patients without alloplastic
      augmentation (32.6%). Whereas preperitoneal mesh repair is convincingly the ideal
      surgical technique, optimization of the alloplastic materials by reduction of the
      amount of foreign substance and improvement of elasticity and biocompatibility is
      mandatory.

PMID- 9011423
TI  - ["Tension-free" repair of inguinal hernia: laparoscopic (TAPP) versus open
      (Lichtenstein) repair].
AB  - In a prospective study, from June 1992 to February 1994 94 patients with 100
      hernias were treated laparoscopically (TAPP) and from March 1993 to November 1994
      100 patients with 108 hernias were treated with a Lichtenstein patch. Concerning
      duration of operation, postoperative outcome, complications and return to work,
      only minor differences were noted. Because of the more demanding and difficult
      technique, all TAPP procedures were performed by one surgeon, whereas all 11
      surgeons of the department performed the Lichtenstein procedure without any
      learning curve, which demonstrates the simplicity of the procedure. A higher
      recurrence rate was found for the TAPP procedure (8 vs 0), however the learning
      curve has to be considered. The Lichtenstein operation is easy to learn and
      perform, safe, efficient, cheaper (750 DM) and therefore superior to the TAPP
      procedure. A planned randomized study was cancelled; laparoscopic hernia repair
      is no longer carried out in our department.

PMID- 9011424
TI  - [Comparative study of various 2-D and 3-D vision systems in minimally invasive
      surgery].
AB  - The aim of this comparative study was to gain subjective and objective data to
      determine for which operative tasks it is useful to work with 3-D rather than 2-D
      vision systems and to show the advantages and disadvantages of 3-D systems. A
      series of five standardized tasks like sewing and tying knots was set up to
      measure performance times objectively and to count errors. Compared with 2-D
      vision, the performance time was 32% shorter and 43% fewer errors were made under
      3-D vision (P < 0.001). In our endoscopic training centre, surgeons involved in
      basic and advanced laparoscopic courses trained using both 2-D and 3-D vision
      systems. They subsequently completed analogue scale questionnaires to record a
      subjective impression of comparative ease of operation tasks under 2-D and 3-D
      vision, and to identify perceived deficiencies in the 3-D system. In both
      courses, all operative tasks were judged significantly easier under 3-D vision (P
      < 0.001). It was concluded that users with a normal capacity for spatial
      perception can work faster and safer under 3-D vision, especially for more
      complicated surgical manoeuvres.

PMID- 9011425
TI  - [Late abscess after laparoscopic cholecystectomy caused by lost gallstones].
AB  - A possible intraoperative complication of laparoscopic cholecystectomy is opening
      of the gallbladder with subsequent loss of gallstones. We report on a 61-year-old
      woman who was hospitalised with an obscure subhepatic tumor. Intraoperatively an
      abscess was found that had been caused by lost gallstones following after
      laparoscopic cholecystectomy 3 years previously. There is a low incidence of late
      abscesses caused by loss of gallstones, but because of the long latency and
      unspecific symptoms there may be problems in diagnosis. Taking into consideration
      possible complications caused by intraoperative loss of gallstones, all
      concrements should be retrieved, even though there is no indication for changing
      to an open procedure.

PMID- 9011426
TI  - [Incarcerated diaphragmatic hernia as a sequela of iatrogenic diaphragmatic
      defect. 2 case reports].
AB  - We describe two cases of iatrogenic adult diaphragmatic hernias with
      incarceration which occurred postoperatively and led to an acute abdomen. The
      pathogenesis, clinical findings, the often challenging diagnostics and the
      therapeutic management of this rare condition are discussed.

PMID- 9011427
TI  - [The 100th birthday of Rudolf Nissen].
AB  - Rudolf Nissen was born in Neisse, Schlesien, 9 September 1896. From 1921 to 1933
      he was the favorite pupil of Ferdinand Sauerbruch in Munich and Berlin. 1930 he
      became professor of surgery at the Charite. The assumption of power by the Nazi
      regime forced Nissen to resign his position and end his career in Germany. He
      took over the surgical chair in Istanbul, Turkey. Emigrating in 1939 to the USA,
      he held surgical positions in hospitals at New York and accepted in 1952 the
      chair of Surgery at the University of Basel, Switzerland. Nissen died in Riehen/
      Basel on 22 January 1981. Nissen was a critical observant clinician, an efficient
      and popular physician, a teacher and a speaker. Of historical significance are
      pioneering works in thoracic surgery, the first successful pneumectomy in man,
      the classical works about the treatment of gastro-oesophageal reflux disease and
      hiatus hernia. The Nissen-Rossetti type of fundoplication has remained the
      standard procedure in Europe and the USA.

PMID- 9011428
TI  - [Effect of molecular diagnostic procedures on surgical therapy of malignant
      diseases].
AB  - In the past molecular biological techniques have provided the basis for
      principally new aspects in the diagnosis of neoplastic diseases. The genetic
      predisposition to hereditary cancer syndromes can be detected by germ line DNA
      sequence analysis and offers the opportunity for prophylactic surgery. Some
      preneoplastic lesions can be detected through the identification of specific
      molecular alterations in nucleic acid preparations derived from various clinical
      samples. Residual or disseminated tumor cells can be detected in resection
      margins, lymph nodes, bone marrow, or peripheral blood with great sensitivity.
      Most likely, these techniques will strongly influence cancer screening programs
      and provide a rational basis for adjuvant systemic or regional therapy
      modalities. However, the clinical value of these techniques has not yet been
      proven in controlled trials. The problems of reproducibility and quality
      assurance have to be addressed and solved. This review summarizes the basic
      principles of some of these new molecular diagnostic techniques to permit a
      critical assessment of their clinical implications.

PMID- 9011429
TI  - [Gene therapy--current status and outlook].
AB  - None of the human gene transfer studies to date has shown definitive proof of
      clinical efficacy, despite more than 100 clinical protocols involving nearly 600
      patients. In spite of the lack of positive results, tremendous hope permeates the
      field, biotechnology companies are getting started and raising millions of
      dollars from venture capital, and patients all over the world are agreeing to
      enroll in protocols involving this technology. Critics of the field claim that
      gene therapy has been overemphasized by researchers in academia, government and
      industry and by the scientific and popular media. Supporters of the field argue
      that the state of gene therapy is no different than other experimental therapies
      in its early stages. During the early stages of chemotherapy, agents were tested
      on hundreds of patients, often with a similar level of hope and no clinical
      effects. Despite the many controversies, one issue is shared by both groups: all
      of them recognize the tremendous potential of this technology to have an impact
      on human disease and share hope for long-term results.

PMID- 9011430
TI  - [Telemedicine--technical possibilities and practical applications].

PMID- 9011431
TI  - [Indications for liver transplantation in severe amanita phalloides mushroom
      poisoning].
AB  - The clinical course of 12 patients with mushroom poisoning was evaluated in order
      to define the parameters considered to be relevant to the indication for liver
      transplantation. Eight patients recovered under conservative therapy; one patient
      died due to pre-existing, concomitant cardiopulmonary disease. In three patients
      transplantations had to be performed because of severe liver failure. On
      admission, the transplanted patients had a decreased Quick's test score and
      factor V value (< 10%). The peak of liver enzymes, serum bilirubin, serum
      creatinine, partial thromboplastin time and azotemia were not of any prognostic
      value. Main indications for liver transplantation were a very low initial Quick's
      test score and factor V value (both < 10%) and their inadequate response under
      substitution therapy. The development of encephalopathy and renal failure were
      further parameters indicating poor prognosis.

PMID- 9011432
TI  - Magnetoenterography (MENG): noninvasive measurement of bioelectric activity in
      human small intestine.
AB  - The basic electrical rhythm (BER) of the gastrointestinal tract creates minute
      magnetic fields that have been measured in animals using a Superconducting
      QUantum Interference Device (SQUID) gradiometer. The aim of this study was to
      measure noninvasively the biomagnetic fields of human stomach and small
      intestine. Twenty-one human volunteers were studied using a 37-channel SQUID
      gradiometer positioned over the epigastrium and umbilicus. In one volunteer
      additional biomagnetic recordings were performed in order to map the spatial
      variation of the biomagnetic fields. Cyclical waveforms consistent with gastric
      BER [3.0+/-0.5 cycles per minute (cpm)] and small intestine BER (10.26+/-1.74
      cpm) were seen in the epigastrium and umbilicus, respectively. The mapping study
      identified the expected frequency gradient (12.0 cpm in duodenum, 11.3 cpm in
      jejunum, to 9.7 cpm in ileum) within the small intestine. Noninvasive recordings
      of human gastric and small intestinal BER can be obtained using a SQUID
      gradiometer.

PMID- 9011433
TI  - A radiopaque marker technique for measuring gastrointestinal transit in subjects
      with an ileostomy.
AB  - We aimed to develop a simple, clinically useful technique for measuring gut
      transit time in patients with an ileostomy, in order to distinguish easily when
      patients have fast or slow transit. Seventeen healthy subjects (mean age, 55
      years; range, 43-71 years; nine males) who had had a proctocolectomy for
      ulcerative colitis more than 1 year previously and without small intestinal
      resection were studied. Subjects were studied on 4 days after an overnight fast,
      two studies with and two without breakfast. A standard diet was used on all days.
      Twenty radiopaque markers were given at the start of each study day. Ileostomy
      effluent was collected over 24 hr and x-rayed to determine the number of retained
      markers. Studies with breakfast demonstrated greater intrasubject
      reproducibility. The mean transit time for passage of 50% of markers was 16.6 hr
      with, and 14.8 hr without, breakfast (p < 0.02). From the data obtained we
      suggest that the optimum time for taking a single abdominal radiograph in a
      patient with suspected fast transit is 6 hr after ingestion of markers, while the
      optimum time for a patient with suspected slow transit is 24 hr.

PMID- 9011434
TI  - The effects of gamma-radiation on intestinal motor activity and faecal pellet
      expulsion in the guinea pig.
AB  - The effects of whole-body gamma-radiation (10 Gy) on intestinal motor activity
      was examined in the small and large intestine of the guinea pig 18 hr post
      irradiation. Neurally mediated relaxations of isolated gut bath preparations were
      generally unaffected. However, the contractile responses to direct smooth muscle
      stimulation with the cholinergic muscarinic agonist carbachol or ganglionic
      stimulation of intrinsic cholinergic motor neurones were significantly increased
      in the duodenum and colon but not the jejunum. This increased sensitivity to
      cholinergic stimulation was reflected in an increased contractility and a shift
      in the concentration-response curves for carbachol. The specificity of radiation
      actions for cholinergic mediated contractions was further supported by the
      observation that histamine-evoked contractions were unaffected. In a second
      series of experiments we examined the effects of gamma-radiation on the rate of
      pellet expulsion from freshly excised colons. Both colons from irradiated animals
      and nonirradiated colons exposed to carbachol showed significantly faster rates
      of pellet expulsion, indicative of increased propulsive motility. Pretreatment of
      animals with 0.5 mg/kg sc of the 5HT3 receptor antagonist Granisetron prevented
      the effect of radiation and reduced the pellet expulsion rate to below normal.
      These results indicate that gastrointestinal motility disturbances seen in organ
      bath preparations of the intestine from rats exposed to whole-body gamma
      radiation may be related to an increased sensitivity of the cholinergic
      muscarinic system.

PMID- 9011435
TI  - Jejunal brake.

PMID- 9011436
TI  - Effects of calcisorb on fecal bile acids and fatty acids in human volunteers.
AB  - The intake of calcium (Ca) is negatively associated with colorectal cancer (crc)
      risk. The aim of this study was to investigate in a double-blind, placebo
      controlled trial, the effects of the Ca-binder Calcisorb, which is given to
      kidney stone patients with hypercalciuria type I, on risk factors for crc risk,
      bile acids (BA), and long-chain fatty acids (LCFA) in fecal water. Results show
      that the concentration of BA and LCFA in fecal water did not change, although the
      urinary excretion of Ca and magnesium (Mg) and the concentration of Ca and
      magnesium in fecal water decreased. The daily excretion of BA and LCFA acids
      decreased significantly (p < 0.05) during the Calcisorb period. In conclusion,
      binding dietary Ca and Mg with Calcisorb from a diet with a relatively low amount
      of fat does not enhance the solubility of BA and LCFA in fecal water.

PMID- 9011437
TI  - Cytological vs microhistological diagnosis of hepatocellular carcinoma:
      comparative accuracies in the same fine-needle biopsy specimen.
AB  - There is still debate over the relative merits of cytology and histology in
      diagnosing hepatocellular carcinoma in cirrhotic livers. Previous comparisons of
      the diagnostic accuracies of these two methods may have been biased by sampling
      errors due to multiple punctures. We compared the diagnostic accuracies of
      cytology and microhistology using tissue and cells from the same point in liver
      nodules subsequently proved to be hepatocellular carcinoma. A single ultrasound
      guided liver-nodule biopsy was obtained with a 20- to 21-G cutting needle from
      131 cirrhotic patients. The solid portion of samples was used for microhistology;
      the remainder was subjected to smear cytology. The results of each type of
      examination were expressed as true positive, nonspecific malignancy, false
      negative, or inadequate for diagnosis. No false-positive diagnoses were made in
      13 benign lesions. In 118 HCC nodules (particularly those <30 mm in diameter),
      cytology provided a significantly higher percentage of correct diagnoses (85.6%)
      that was only slightly inferior to that based on results of both studies (89.8%).
      The single-biopsy technique generally provides adequate tissue for histology and
      cytology specimens with a high cellularity. It reduces both the cost and the
      risks of fine-needle biopsy diagnosis of hepatocellular carcinoma.

PMID- 9011439
TI  - Case report: gastric carcinoma as a complication of dyskeratosis congenita in an
      adolescent boy.
AB  - Dyskeratosis congenita (DC), or the Zinsser-Engman-Cole syndrome, is a rare X
      linked heritable disorder, affecting primarily the ectodermal tissues, with
      hyperpigmentation of the skin, leukoplakia of the buccal and anal mucosa, and
      nail dystrophy (1, 2). Aplastic anemia (3) and a variety of neoplasms (4, 5) are
      some of the extraectodermal manifestation of this disorder, which although X
      linked recessive, has also been described in a few females (6, 7). Mental
      retardation, diarrhea, and gastrointestinal bleeding have been considered to be
      less frequent features (8). We report an adolescent Indian male who presented
      with all the ectodermal manifestations, as well as mental retardation, bone
      marrow aplasia, and gastrointestinal hemorrhage secondary to adenocarcinoma of
      the stomach.

PMID- 9011438
TI  - Unresectable hepatocellular carcinoma in cirrhosis: survival, prognostic factors,
      and unexpected side effects after transcatheter arterial chemoembolization.
AB  - To evaluate the efficacy of transcatheter arterial chemoembolization in the
      treatment of hepatocellular carcinoma, the prognostic factors, and the side
      effects, 72 patients undergoing 170 chemoembolizations with lipiodol-mediated
      injection of adriamycin were investigated. The 1-, 2-, and 3-year survivals are
      83, 61, and 56%, respectively. Significant prognostic factors for survival (by
      Mantael-Haenszel) are Child-Pugh and Okuda status (p = 0.00001 and p = 0.01
      respectively), number of TACE courses (p = 0.002) and of courses completed with
      embolization (p = 0.05), stabilization or reduction of alpha-fetoprotein (p =
      0.003), and concurrent tamoxifen treatment (p = 0.04). Side effects included
      fever, pain, increased serum amylase and transaminase levels, and one liver
      abscess with death of liver failure. In addition, mild hyperglycemia was observed
      in 19% of patients and severe in 8% (with one hyperosmolar diabetic coma), in the
      absence of pancreatic damage. In conclusion, transcatheter arterial
      chemoembolization is useful in patients with unresectable hepatocellular
      carcinoma. Prognostic factors are Child-Pugh and Okuda status, number of TACE
      courses and of embolizations, changes of alpha-fetoprotein levels, and
      association with tamoxifen treatment. The development of mild to severe changes
      of glucose metabolism suggests that glucose tolerance should be evaluated before
      and glycemia strictly monitored after each TACE course.

PMID- 9011440
TI  - Case report: primary CD30 (Ki-1)-positive anaplastic large cell lymphoma of the
      duodenum.
AB  - As recently described, Ki-1 anaplastic large cell lymphoma is a distinctive
      subtype of non-Hodgkin's lymphoma. We report a Ki-1 anaplastic large cell
      lymphoma of the duodenum in a 62-year-old man. He received modified CHOP therapy
      and was in complete remission at 18 months. To our knowledge, this is the first
      report of primary Ki-1 anaplastic large cell lymphoma of the duodenum.

PMID- 9011441
TI  - Diagnostic efficacy of push-enteroscopy and long-term follow-up of patients with
      small bowel angiodysplasias.
AB  - Gastrointestinal angiodysplasias are the most common cause of obscure chronic
      digestive blood loss. Push-enteroscopy is likely to detect and to treat vascular
      lesions. Push-enteroscopy was performed in 83 patients (mean age 62 years)
      presenting with iron deficiency anemia of obscure origin. A nonrevealing
      preliminary evaluation included esophagogastroduodenoscopy, colonoscopy and, in
      50% of the patients, small bowel barium studies. We employed a 240-cm Olympus
      push-enteroscope (XSIF-100), 11.3 mm in diameter. A potential bleeding lesion was
      observed in 49 patients (59%). Gastrointestinal angiodysplasias were the most
      common lesion (33 patients). Electrocoagulation (bicap) of angiodysplasias was
      performed when accessible and not diffuse (<20). If not contraindicated, hormonal
      treatment was proposed for patients who had at least five AD. Some patients had
      both treatments. Long-term follow-up (mean, 12.2 months) was obtained in 25
      patients with small bowel angiodysplasias. A good outcome (neither recurrence of
      anemia nor blood transfusion requirements) was observed in 12 patients. The
      diagnostic efficacy of push-enteroscopy is high. Despite available and
      recommended therapeutic modalities, the long-term outcome was considered to be
      good in only 50% of the patients.

PMID- 9011442
TI  - A study at 10 medical centers of the safety and efficacy of 48 flexible
      sigmoidoscopies and 8 colonoscopies during pregnancy with follow-up of fetal
      outcome and with comparison to control groups.
AB  - To analyze the risks versus benefits of flexible sigmoidoscopy and colonoscopy to
      the pregnant female and fetus, we conducted a multiyear, retrospective study at
      10 hospitals of 46 patients undergoing 48 sigmoidoscopies and 8 patients
      undergoing 8 colonoscopies during pregnancy. Sigmoidoscopy controls included two
      study control groups and the average American pregnancy outcomes. Sigmoidoscopy
      indications included hematochezia in 28, diarrhea in 10, abdominal pain in 4, and
      other in 3. Thirteen patients were in the first trimester of pregnancy, 18 were
      in the second trimester, and 15 were in the third trimester. Twenty-seven
      patients had a lesion diagnosed by sigmoidoscopy, including reactivated or newly
      diagnosed inflammatory bowel disease, bleeding internal hemorrhoids, and other
      colitidies. Twenty-two of 29 patients with rectal bleeding had a significant
      lesion identified by sigmoidoscopy. Sigmoidoscopy was significantly more
      frequently diagnostic for hematochezia than for other indications (p < 0.03,
      chi2). No endoscopic complications occurred to the pregnant patients. Excluding 4
      voluntary abortions and 1 unknown pregnancy outcome, 38 (93%) of 41 pregnant
      females delivered healthy babies (study control rate = 93%; NS, Fisher's exact
      test). Mean live-born infant Apgar scores were 8.2+/-1.5 (SD) at 1 min and 9.0+/
      0.2 at 5 min (control mean Apgar scores: 8.1+/-1.7 at 1 min and 8.8+/-1.0 at 5
      min; NS, Student's t test). Three high-risk pregnancies ended with fetal demise
      at 8, 9, or 12 weeks after sigmoidoscopy, from causes unrelated to sigmoidoscopy.
      No fetal cardiac abnormalities were detected by fetal cardiac monitoring during
      two sigmoidoscopies. Eight pregnant females underwent colonoscopy, without
      complications. Pregnancy outcomes included six healthy babies delivered at full
      term, one voluntary abortion, and one fetal demise in a high-risk pregnancy 4
      months after colonoscopy from causes unrelated to colonoscopy. This study
      suggests that sigmoidoscopy does not induce labor or result in congenital
      malformations, that sigmoidoscopy is not contraindicated during pregnancy, and
      that sigmoidoscopy may be beneficial in pregnant patients with significant lower
      gastrointestinal bleeding. Colonoscopy during pregnancy should be considered for
      life-threatening lower gastrointestinal bleeding or when the only alternative is
      surgery.

PMID- 9011443
TI  - Acute gastric anisakiasis: 28 cases during the last 10 years.
AB  - Anisakiasis is a disease which occurs following eating raw fish infected with
      anisakis larvae. Many cases have been reported from Japan and from other
      countries with increasing opportunities of eating raw fish such as "sushi" and
      "sashimi." We have reviewed 28 patients with acute gastric anisakiasis during the
      last 10 years from November 1984 to October 1994. This disease has rarely been
      detected in persons over 60 years of age and in patients with gastric surgery.
      Therefore it is postulated that gastric acid secretion influences the activities
      of anisakis larvae. An alkaline gastric pH could interfere with the toxicity of
      anisakis larvae.

PMID- 9011444
TI  - The presence of Helicobacter pylori in nonoperated duodenal ulcer patients
      compared to patients late after highly selective vagotomy.
AB  - There are many recent studies that clearly suggest that Helicobacter pylori (HP)
      is an etiological agent for duodenal ulcer disease (1-3). Randomized trials have
      shown that duodenal ulcers treated by omeprazole or H2 blockers heal faster if HP
      is eradicated concurrently (4-6). Besides, several studies have demonstrated that
      eradication of HP significantly reduces duodenal ulcer relapses (7-9). Patients
      followed up to 7 years after eradication of HP demonstrated that 92% remained HP
      negative, with only 3% recurrence (10). Highly selective vagotomy has been the
      treatment of choice for duodenal ulcer patients who are candidates for surgical
      therapy (11, 12). The late results have shown an approximately 10% recurrence
      rate 8 to 10 years after surgery (13, 14). We hypothesized that in these
      asymptomatic cases after HSV, HP probably will exist in a minor proportion of
      cases, similar to what happens after successful medical antiulcer therapy.
      Therefore the purpose of the present study was to determine the HP status at the
      antrum in a group of nonoperated duodenal ulcer patients compared to a group
      submitted to highly selective vagotomy many years prior to the actual study.

PMID- 9011445
TI  - Characteristics of the propagating pressure wave in the esophagus.
AB  - Understanding the relationships of intraluminal manometric events to bolus
      transit through the esophagus has been limited by conventional manometric
      analysis methods. We reconstructed pressure events in the axial direction in
      order (1) to describe the peristaltic pressure wave as it propagates through the
      esophagus in the direction of the bolus and (2) to determine what sampling
      interval along the esophageal length is required for accurate representation.
      Esophageal manometric studies using the stepwise withdrawal method were performed
      in 10 asymptomatic volunteers. Propagating wave forms were created at 0.2-sec
      intervals and analyzed in static and dynamic fashion from averaged waves at each
      1-3 cm of esophageal length. A distinctive and similar appearance to the
      propagating wave form, comprised of three sequential but overlapping contraction
      segments in the esophageal body, was present in nine subjects. The propagating
      wave decelerated as it approached the second region (smooth-muscle esophagus) and
      extended over as much as 15.1+/-0.7 cm of esophageal length. No significant
      differences in wave front propagation, length, or velocity could be determined if
      the sampling interval increased from 1 to 3 cm of esophageal length, but peak
      amplitudes were reduced by as much as 14.2%. We conclude that the esophageal
      pressure wave, when viewed in the direction of bolus transit, is broad and
      typically comprised of three sequential contraction components. Sampling at >1-cm
      intervals along the esophageal length significantly alters the wave appearance
      and may be unsatisfactory in the distal esophagus. Axial transformations of
      manometric data potentially will provide better information concerning the
      neuromuscular control of peristalsis and events responsible for bolus movement.

PMID- 9011446
TI  - Three-dimensional imaging of the lower esophageal sphincter in healthy subjects
      and gastroesophageal reflux.
AB  - The resting pressure and intraabdominal length are the most important factors
      which determine competence of the lower esophageal sphincter (LES). The
      intraabdominal sphincter vector volume (ISVV) is a single value which takes into
      account both of these measurements. Normal values of ISVV and of the total
      sphincter vector volume (TSVV) were established in 20 normal subjects. The
      sensitivity and the specificity of ISVV and TSVV were then evaluated in 81
      patients with gastroesophageal reflux disease (GERD) and in 19 normal subjects
      and were compared with the usual stepwise pullback manometry (SPM) measuring the
      resting pressure of the LES at the respiratory inversion point. The motorized
      pullthrough technique was used to perform the vector volume procedure. Normal
      values of ISVV were 1870-10740 mm Hg2 x mm, and of TSVV 2200-13110 mm Hg2 x mm.
      The sensitivity of ISVV was 93.8% (p < 0.05), of TSVV 80.2%, and of SPM 81.5%.
      The specificity of ISVV and TSVV was 89.5% and of SPM 78.9% (not significant).
      Analysis of the intraabdominal sphincter vector volume is more sensitive than the
      total sphincter vector volume or standard stationary manometry in establishing a
      defective LES in patients with GERD. Intraabdominal sphincter vector volume
      analysis will allow surgeons better to identify patients with a defective LES who
      may be suitable for antireflux surgery.

PMID- 9011447
TI  - Brain ischemia and gastric mucosal damage in spontaneously hypertensive rats: the
      role of arterial vagal adrenoceptors.
AB  - Brain ischemia is often accompanied by acute gastric lesions. To clarify the
      underlying mechanism, the influence of acute ischemic insult to the brain on
      gastric hemodynamics and mucosal integrity was examined in spontaneously
      hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow
      decreased to 71% of the preischemic levels in the control rats but was preserved
      significantly better, at 94 and 108%, in the prazosin-treated and guanethidine
      treated rats, respectively. Vagotomy almost abolished the decrease in gastric
      mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid
      administered just after reperfusion induced more severe hemorrhagic ulcers in the
      control than in the prazosin-treated and vagotomized groups. These results
      suggest that noradrenergic neurons acting through alpha1-adrenoceptors
      contributes to the decrease in gastric mucosal blood flow, and the subsequent
      disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway
      during brain ischemia in spontaneously hypertensive rats.

PMID- 9011448
TI  - Effect of octreotide on sphincter of Oddi motility in patients with acute
      recurrent pancreatitis: a manometric study.
AB  - Sphincter of Oddi dysfunction has been reported as a cause of acute idiopathic
      recurrent pancreatitis (IRP). Octreotide, a long-acting somatostatin analogue, is
      an antisecretory drug used in the treatment and prevention of acute pancreatitis.
      Its action on sphincter of Oddi motility is controversial and no data are
      available for IRP patients. The aim of this study was to assess sphincter of Oddi
      motor response to acute administration of octreotide in patients with past
      attacks of acute pancreatitis without identification of any evident aetiological
      factor. Six patients (four male, two female; mean age +/-SD, 38.8+/-9 years)
      suffering from acute pancreatitis for at least 3 months before the examination
      were submitted to sphincter of Oddi manometry. After a basal recording lasting at
      least 2 min, octreotide, 0.05 mg i.v., was administered and the recording
      repeated. Intraduodenal pressure was taken as the zero reference and the basal
      sphincter of Oddi pressure and amplitude and frequency of phasic contractions
      were calculated before and after octreotide administration. No significant pre-
      vs post-octreotide differences were observed in basal pressure (41.9+/-24 vs
      47.5+/-33 mm Hg, respectively) or in amplitude of phasic contractions (164.6+/-33
      vs 170.8+/-18 mm Hg). With a latency of about 1 min, octreotide administration
      caused a high-frequency phasic activity in all cases (mean frequency, 5.5+/-2.2
      contractions/min before and 9.8+/-2 after octreotide; P < 0.04). After the
      procedure acute pancreatitis (prolonged abdominal pain and serum amylase levels
      more than three-fold the normal values) developed in five patients. In
      conclusion, our data suggest that acute administration of octreotide may induce
      tachyoddia and thus a rise in sphincter of Oddi pressure, with possible
      impairment of biliary-pancreatic outflow.

PMID- 9011449
TI  - ESWL experience in the therapy of difficult bile duct stones.
AB  - In recent years, alternatives to surgery for difficult bile duct stones have been
      developed. Routine endoscopy fails in about 10% of patients. To verify the role
      of extracorporeal shock wave lithotripsy in residual CBD stones, we treated 32
      patients by HM4 or MPL 9000 Dornier lithotripters. Ten (34.4%) patients needed
      two extracorporeal shock wave lithotripsy sessions, and 3 (10.3%) patients three.
      Complete clearance was achieved in 29 patients (90.6%) after one or more sessions
      either by endoscopic (20 pts) or percutaneous (9 pts) extraction of the debris;
      of the remaining 3 patients, in 2 a bilioduodenal stent was placed and in 1
      electrohydraulic lithotripsy was performed. Eighteen and seven-tenths percent
      transient mild hemobilia, 12.5% microhematuria, and no mortality were observed.
      It is possible to state that in site- or size-related difficult biliary stones,
      extracorporeal shock wave lithotripsy is a rapid, safe, and highly effective
      treatment as an additional nonoperative option to resolve the failure of routine
      endoscopic measures.

PMID- 9011450
TI  - Influence of orlistat on the regulation of gallbladder contraction in man: a
      randomized double-blind placebo-controlled crossover study.
AB  - Orlistat (tetrahydrolipstatin) is a potent inhibitor of gastric and pancreatic
      lipase activity causing a diminution of free fatty acids in the intestinal lumen.
      The release of cholecystokinin (CCK) critically depends on the presence of free
      fatty acids in the small intestine. Postprandial CCK release and gallbladder
      contraction might be decreased by orlistat, potentially resulting in an increased
      risk of gallstone formation. In this double-blind, placebo-controlled, six-way
      crossover study, six healthy volunteers ingested in a randomized order three
      isocaloric test meals (250 ml) of identical osmolality with either orlistat (200
      mg) or placebo: (a) a pure-fat meal (25 g triglycerides), (b) a mixed meal
      containing fat (8 g; 29% of caloric content), protein (10 g; 17%), and dextrose
      (32 g; 54%), and (c) a fat-free meal containing albumin (25 g; 46%) and dextrose
      (32 g; 54%). Gallbladder volumes were determined by ultrasonography, and plasma
      CCK, pancreatic polypeptide and gastrin levels by RIA. Gall-bladder contraction
      (AUC, % x 90 min; difference of means +/- 95% CI) in subjects receiving orlistat
      or placebo did not significantly differ after intake of the pure-fat meal (443+/
      1174), the mixed meal (313+/-1170), or the fat-free-meal (-760+/-1180). The
      release of CCK (AUC; pM x 90 min; difference of means +/- 95% CI) was not
      different between orlistat and placebo after ingestion of the pure-fat meal (
      18+/-64), the mixed meal (-45+/-62), and the fat-free meal (27+/-63). Likewise,
      the release of pancreatic polypeptide and gastrin was similar after intake of the
      meals with either orlistat or placebo. A single dose of orlistat did not reduce
      gallbladder motility after ingestion of meals with differing fat contents. The
      safety of long-term treatment with orlistat with respect to gallstone formation
      remains to be determined.

PMID- 9011451
TI  - Biliary electrolytes and enzymes in patients with and without gallstones.
AB  - pH, osmolarity, various electrolytes, nine enzymes, and bile acid were determined
      in hepatic and gallbladder biles from 108 and 100 patients, respectively,
      relating to various types of gallstones. The pH, osmolarity, and electrolytes
      were essentially identical in all groups of patients except for slightly higher
      Ca and Mg in the hepatic bile in patients with muddy pigment stones. The
      gallbladder bile contained much higher inorganic cations yet remained isosmotic
      as a result of their sequestration into bile acid micelles. Excluding extremely
      high values, the activities of nine enzymes in the bile showed only minor
      differences among four groups of patients except for a high beta-glucuronidase
      activity in the hepatic bile in patients with muddy pigment stones. The biliary
      baseline activities of various enzymes and the relation to their serum levels
      were determined by their sources and subcellular localization in the hepatocytes.
      We concluded that biliary electrolytes and enzymes were basically similar in
      patients with and without gallstones except for higher levels of Ca, Mg, and beta
      glucuronidase in hepatic bile in patients with muddy pigment stones.

PMID- 9011452
TI  - Ileal absorption of bile acids in patients with chronic cholestasis: SeHCAT test
      results and effect of ursodeoxycholic acid (UDCA).
AB  - The effect of cholestasis on ileal bile acid absorption is controversial in
      animal models (up- or down-regulation) and unknown in humans. We therefore
      studied values of the selena homotaurocholic acid (SeHCAT) test before and after
      long-term administration (>3 months, 13-15 mg/kg/day) of ursodeoxycholic acid
      (UDCA) in 27 patients with chronic cholestatic liver diseases (24 women, 3 men;
      mean age, 50 years; 24 primary biliary cirrhosis, 2 secondary biliary cirrhosis,
      2 others). The control group consisted of 14 healthy volunteers. Seven-day SeHCAT
      percentage retention was identical in the 12 untreated cholestatic patients
      (serum bilirubin, 75+/-42 micromol/L, alkaline phosphatase, 4.2+/-1.0 N; mean+/
      SEM) and in the control group (43.6+/-2.9 and 43.8+/-4.2%, respectively). In the
      22 patients treated by UDCA for 38+/-8 months, SeHCAT percentage retention was
      20.3+/-3.0%. In the seven patients with the SeHCAT test done before and after
      UDCA treatment (16+/-5 months), SeHCAT percentage retention decreased
      significantly under UDCA therapy (42.0+/-4.4 vs 19.4+/-4.1%; P < 0.02). We
      conclude that, in patients with chronic cholestasis (1) SeHCAT percentage
      retention is not altered-taken together with the known defect of biliary
      excretion, this lack of increase in SeHCAT percentage retention argues against up
      regulation of bile acid ileal transport; and (2) UDCA treatment induces a
      decrease in the SeHCAT percentage retention-this effect may be related primarily
      to a decreased bile acid ileal absorption.

PMID- 9011453
TI  - Gallstone formation and gallbladder bile composition after colectomy in dogs.
AB  - A high prevalence of gallstones has been described in patients following
      colectomy. The aim of this study was to examine whether lithogenicity is
      attributed to colectomy. In the present study, changes in gallbladder bile
      composition and the mechanism of gallstone formation after colectomy were
      examined in dogs. Ten mongrel dogs underwent restorative proctocolectomy. Seven
      dogs which received sham operations served as controls. Over a 12-week
      postoperative period, samples of gallbladder bile, formed gallstones and serum
      were collected and analyzed. In 7 of the 10 (70%) colectomized dogs, gallstones
      were found in the gallbladder, while the control dogs had no stones.
      Macroscopically the gallstones were similar to black pigment stones observed in
      humans. Chemical analysis and Fourier transform-infrared spectroscopy examination
      revealed that the stones were composed mainly of sodium bilirubinate and
      proteins, with minor amounts of calcium salts and cholesterol. Significant
      increases in biliary pH and concentrations of ionized calcium and unconjugated
      bilirubin were observed in the gallbladder bile of the colectomy group compared
      with that of the control group. The total bile acid and total bilirubin
      concentrations were significantly decreased in the colectomy group. Cholesterol
      crystal nucleation did not occur. The inhibitory effect of gallbladder bile on
      calcium carbonate precipitation in an in vitro assay system was preserved even
      after colectomy. In conclusion, proctocolectomy increases the concentration of
      unconjugated bilirubin in gallbladder bile and induces pigment gallstones which
      are composed mainly of sodium bilirubinate and proteins since calcium ions and
      cholesterol are stabilized in dogs.

PMID- 9011454
TI  - Role of endogenous hypergastrinemia in regenerating endocrine pancreas after
      partial pancreatectomy.
AB  - We studied the possible role of endogenous gastrin in the regenerating pancreas.
      Male Wistar rats underwent sham operation or 90% partial pancreatectomy (Px).
      Lansoprazole (30 mg/kg body wt), a proton pump inhibitor (PPI), was given p.o.
      for 3 weeks after surgery. Plasma glucose levels were higher in Px rats than in
      shams. Lansoprazole lowered plasma glucose levels in the Px rats. In addition,
      integrated insulin secretion during an oral glucose tolerance test (2 g/kg body
      wt) was significantly (p < 0.01) higher in lansoprazole-treated Px rats than in
      control Px rats, while lansoprazole did not affect insulin secretion in shams.
      Fasting serum gastrin levels were higher (p < 0.01) in lansoprazole-treated
      animals than in controls both in sham rats and in Px rats. Furthermore,
      lansoprazole increased the pancreas weight per body weight and elevated the
      insulin content of the pancreas in Px rats. These results suggest that endogenous
      hypergastrinemia has a trophic effect on endocrine pancreas during regenerating
      processes and that administration of PPI may be clinically beneficial to the
      remnant pancreas after pancreatectomy if the whole stomach is preserved.

PMID- 9011455
TI  - Somatostatin reduces gastric mucosal blood flow in patients with portal
      hypertensive gastropathy: a randomized, double-blind crossover study.
AB  - Agents which decrease gastric mucosal blood flow (GMBF) are postulated to have
      beneficial effects in arresting gastrointestinal bleeding in cirrhotic patients
      with portal hypertension. Our objective was to test the hypothesis that in a dose
      that significantly lowers wedged hepatic venous pressure (WHVP), a bolus
      injection of somatostatin will significantly decrease GMBF in patients with
      portal hypertensive gastropathy (PHG). In this placebo-controlled, double-blind,
      crossover study, 20 cirrhotic patients with PHG were randomly assigned to receive
      either somatostatin followed by placebo (Group A) or placebo followed by
      somatostatin (Group B). Wedged hepatic venous pressure was monitored. GMBF in the
      antrum and corpus was assessed by reflectance spectrophotometry. Indices of
      hemoglobin concentration (IHb) and indices of oxygen content (ISO2) were
      recorded. Nine patients were assigned to Group A, and 11 to Group B. Mild PHG was
      seen in 16 patients, and severe PHG in 4 patients. Baseline WHVP, IHb, and ISO2
      were similar in both treatment groups. Wedged hepatic venous pressure (WHVP) was
      significantly lowered [median, 17.6%; interquartile range (-27.0,-12.6%); P =
      0.0008] after a 250-microg bolus injection of somatostatin. This dose of
      somatostatin significantly reduced IHb both in the antrum [-10.2% (-23.4, 0.4%)]
      and in the corpus [-5.8% (-16.6, 5.6%)] compared to placebo (P = 0.02 and 0.04,
      respectively). Intravenous bolus injection of 250 microg somatostatin
      significantly reduces WHVP and GMBF in patients with PHG. Whether this ability to
      decrease the GMBF in PHG makes somatostatin an effective treatment in acute
      gastrointestinal bleeding in PHG deserves to be studied.

PMID- 9011456
TI  - Pathogenesis of chronic liver disease in patients with chronic hepatitis B virus
      infection without serum HBeAg.
AB  - Chronic hepatitis B in patients lacking hepatitis B e antigen has been attributed
      to a hepatitis B virus variant (G-to-A mutation at nucleotide 1896 in the precore
      region of the genome). We therefore assessed the frequency and significance of
      this variant among 43 United States patients (10 with chronic hepatitis B
      seropositive for e antigen, 19 seronegative for e antigen, and 14 healthy
      carriers). Sera were tested for HBV DNA by polymerase chain reaction and branched
      DNA assay. The A1896 variant was detected by direct sequencing and ligase chain
      reaction. Serum HBV DNA was more frequently found among patients with e antigen
      positive than e antigen-negative chronic hepatitis B. Viral titers were generally
      higher in those with e antigen. None of the e antigen-positive and only 24% of e
      antigen-negative patients harbored the A1896 variant. Patients infected with the
      variant were more often Asian, had had hepatitis B for longer and had higher
      levels of viral DNA than HBeAg-negative patients with the wild-type virus. The
      A1896 variant was found exclusively in patients infected with HBV genotypes C and
      D. Thus, the A1896 variant is uncommon in the United States. The activity of
      liver disease appears to be more closely related to the level of HBV replication
      than the presence of mutations at nucleotide 1896 in the genome.

PMID- 9011458
TI  - Pringle maneuver during hepatic resection induces inflammatory cytokines.

PMID- 9011457
TI  - Hepatic Fas antigen expression before and after interferon therapy in patients
      with chronic hepatitis C.
AB  - To assess the relationship between hepatitis C virus infection and Fas antigen
      expression on hepatocytes, we examined changes in hepatic Fas antigen expression
      in the presence or absence of active hepatitis C virus infection. Twenty patients
      with chronic hepatitis C infection were treated with interferon and underwent pre
      and posttreatment liver biopsies. Patients were classified according to the
      absence (group A; n = 9) or the presence (group B; n = 11) of hepatitis C virus
      RNA (HCV-RNA) in the liver after interferon therapy. An immunohistochemical assay
      showed Fas antigen staining in hepatocytes membranes and cytoplasm with
      expression concentrated mainly in periportal areas. The percentage of Fas
      positive cells in the liver before treatment was not different between group A
      (39.5+/-19.1%) and group B (32.5+/-15.6%). Hepatic Fas expression was reduced
      significantly after treatment (24.3+/-10.6%) compared with the pretreatment
      values in group A (p < 0.05) but not in group B (25.9+/-16.9%). There was no
      significant difference between the two groups in the degree of histologic
      improvement. These results suggest that hepatic Fas expression is associated with
      persistent infection of hepatitis C virus.

PMID- 9011459
TI  - Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced
      jejunal mucosal injury.
AB  - Previous reports indicate that intestinal intraluminal ethanol increases mucosal
      permeability (an index of mucosal injury) and histamine release by mast cells,
      and that the released histamine plays a role in mediating the increased
      permeability. In the present study, we investigated whether reactive oxygen
      metabolites and their major sources (xanthine oxidase and leukocytes) were
      involved in these ethanol effects. In rabbits, segments of the jejunum were
      perfused with a control solution or with 6% ethanol. In these segments, mucosal
      permeability was assessed by determining jejunal clearance of i.v. administered
      51Cr-ethylenediaminetetraacetate (51Cr-EDTA) and 125I-bovine serum albumin (125I
      BSA), and mast cell histamine release was estimated from the histamine
      concentration of the gut effluent. Ethanol increased 51Cr-EDTA clearance, 125I
      BSA clearance, and histamine release. These ethanol effects decreased when the
      animals were given superoxide dismutase plus catalase (scavenger of O2- and H2O2,
      respectively), allopurinol, or oxypurinol (xanthine oxidase inhibitors).
      Administration of a monoclonal antibody (R15.7) against leukocyte adhesion
      molecule, CD18, inhibited completely the ethanol-induced increased 51Cr-EDTA and
      125I-BSA clearances and histamine release. These and supplementary data suggest
      that (a) ethanol-induced mucosal injury and mast cell histamine release are
      mediated primarily by leukocytes, and (b) oxy radicals, especially those
      generated by xanthine oxidase, mediate these ethanol effects mainly by promoting
      leukocyte infiltration.

PMID- 9011460
TI  - Intravenous cyclosporine in attacks of ulcerative colitis: short-term and long
      term responses.
AB  - The present study reports the results of intravenous cyclosporine in 32 patients
      with refractory and/or severe attacks of ulcerative colitis (UC). Twenty of 32
      patients responded to intravenous cyclosporine; cyclosporine was clinically
      effective and improved colonic lesions. However, one colonic perforation and one
      postoperative death were observed in two patients with severe endoscopic colitis
      who had failed to reach clinical remission with high-dose corticosteroids and
      cyclosporine. Moreover, after a median follow-up of 190 days, only one-third of
      the patients avoided colectomy. No predictive factor of response to cyclosporine
      was identified. This study confirms that cyclosporine is effective in severe UC
      but suggests that its use could be associated with serious complications in
      patients with severe lesions who had failed to settle with corticosteroids and
      cyclosporine.

PMID- 9011461
TI  - Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa:
      a potential role for these agents in the pathogenesis of ulcerative colitis.
AB  - It has been shown that feces of patients with ulcerative colitis uniformly
      contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes
      with butyrate-dependent energy metabolism of cultured colonocytes and may be
      involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the
      sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were
      incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of
      both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal
      proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase.
      Compared to NaCl, sulfide increased the labeling of the entire crypt
      significantly, by 19% (p < 0.05). This effect was due to an expansion of the
      proliferative zone to the upper crypt (compartments 3-5), where the increase in
      proliferation was 54%. Sulfide-induced hyperproliferation was reversed when
      samples were coincubated with sulfide and butyrate. The study shows that sodium
      hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible
      role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the
      regulation of colonic proliferation and in the treatment of UC.

PMID- 9011463
TI  - Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased
      intestinal permeability.
AB  - Increased intestinal permeability and the CD45RO isoform expression of the
      leukocyte common antigen on peripheral blood CD20+ B cells are found in Crohn's
      disease. Others have observed that multiple sclerosis (MS) patients may have an
      increased risk of coacquisition of Crohn's disease. The aim of this study was to
      identify an association between these diseases using peripheral blood CD45
      isoform expression and intestinal permeability in MS. Lactulose/mannitol
      permeability and peripheral blood CD20+ B cell CD45RO expression were defined in
      healthy controls, MS patients, and patients coincidentally affected by MS and
      Crohn's or MS and ulcerative colitis (UC). Five of 20 MS patients had increased
      intestinal permeability, a finding not previously reported. High levels of CD45RO
      were found on circulating CD20+ B cells from patients with MS. This has not been
      reported previously in MS and is found in very few other conditions. Eight
      patients with coincident MS and Crohn's disease or MS and UC were studied.
      Coincident MS and UC patients expressed CD45RO on CD20+ B cells, a finding not
      identified in UC patients alone. A subgroup of MS patients has increased
      intestinal permeability. These patients express CD45RO CD20+ B cells, also found
      in Crohn's disease.

PMID- 9011462
TI  - IL-1 is an important mediator for microcirculatory changes in endotoxin-induced
      intestinal mucosal damage.
AB  - Although small intestine is frequently injured in endotoxin shock, the exact
      pathological sequence has not been fully understood. The major objective of this
      study is to elucidate the role of interleukin (IL)-1 in endotoxin-induced
      microcirculatory disturbance of rat small intestine. Mucosal and submucosal
      microvessels of the rat ileum were observed by intravital microscope with a high
      speed video camera system and the attenuating effect of E5090, an inhibitor of IL
      1 generation, on endotoxin-induced intestinal microcirculatory disturbances was
      investigated. Endotoxin infusion produced significant mucosal damage, but before
      these morphological changes became significant, microvascular stasis in villi,
      decreased red blood cell velocity, and increased leukocyte adherence to venular
      walls were observed in intestinal microcirculatory beds 30 min after endotoxin
      administration. Intestinal IL-1alpha levels were also significantly increased at
      that time. Endotoxin treatment enhanced chemiluminescence activity from
      neurophils and rapidly mobilized CD18 on leukocytes. E5090, which suppressed the
      IL-1 production in intestinal mucosa, attenuated the microcirculatory
      disturbances induced by endotoxin, and significantly reduced the subsequent
      mucosal damage. E5090 also attenuated the increased chemiluminescence activity
      and CD18 expression on leukocytes. In conclusion, the production of IL-1alpha is
      enhanced in the intestinal mucosa during endotoxin infusion. IL-1 may be an
      important mediator of microcirculatory changes, including decreased red blood
      cell velocity and increased leukocyte sticking and its activation, leading to the
      mucosal damage.

PMID- 9011464
TI  - Case report: a rare case of chylous ascites from Mycobacterium avium
      intracellulare in a patient with AIDS: review of the literature.
AB  - Chylous ascites is a rare complication of acquired immunodeficiency syndrome
      (AIDS). Although it is most commonly associated with lymphoma, it has been
      reported in patients with Kaposi's sarcoma. There has been only one case reported
      of chyloperitoneum occurring in a pediatric patient as a result of Mycobacterium
      avium intracellulare (MAI). We report the first case of an adult patient with
      chylous ascites resulting as a complication of MAI. Chylous ascites
      (chyloperitoneum) is a rare complication of acquired immunodeficiency syndrome
      (AIDS). Only two cases of chylous ascites associated with AIDS have been reported
      in the literature (1, 2). In one case, chylous ascites was attributed to
      extensive abnormal Kaposi's sarcoma (1). In the second case, a 2-year-old child
      with Mycobacterium avium intracellulare (MAI) developed chylous ascites. (2) We
      report the first adult case of AIDS which has been complicated by a MAI infection
      causing mesenteric lymphadenopathy and chylous ascites.

PMID- 9011465
TI  - Chronic HCV infection: public health threat and emerging consensus. Vienna,
      Austria, October 27-28, 1995.

PMID- 9011466
TI  - Dose increase augments response rate to interferon-alpha in chronic hepatitis C.
AB  - Approximately 50% of patients with chronic hepatitis C respond to treatment with
      interferon-alpha. The aim of this randomized controlled trial was to evaluate
      whether an increase in dose of interferon-alpha augments response rate. One
      hundred thirty-eight patients with newly diagnosed chronic hepatitis C received a
      three-month course of 3 MU IFN-alpha2b administered every two days. All patients
      were anti-HCV and HCV-RNA (PCR) positive. Prior to treatment, a liver biopsy was
      performed. Complete response was defined by normal serum ALT concentrations and
      disappearance of HCV-RNA. After three months, 60 nonresponders were randomized
      (stratified according to histology) either to continue 3 MU interferon-alpha2b
      every two days for another six months (group A, total dose: 410 MU) or to receive
      increasing doses of interferon-alpha2b (6 MU every two days for three months,
      followed by 10 MU every two days for three months) (group B, total dose: 870 MU).
      Serum ALT concentrations were measured monthly and HCV-RNA at three-month
      intervals. Liver biopsy was repeated six months after end of treatment.
      Pretreatment characteristics of the randomized patients were: group A: N = 30;
      male/female: 20/10; age: 54 +/- 10 years; CPH 9, CAH 8, cirrhosis 13; mean ALT
      108 +/- 98 units/liter; group B: N = 30; male/female: 21/9; age: 57 +/- 15 years;
      CPH 10, CAH 9, cirrhosis 11; mean ALT 90 +/- 40 units/liter. At the end of
      treatment six patients in group B but none in group A became responders [P =
      0.011 (Fisher's exact test), intent-to-treat analysis]. All six responders were
      noncirrhotics. High-dose interferon was not tolerated by six patients in group B.
      Noncompliance resulted in five dropouts in group A and one in group B. During the
      six-month follow-up, four of the six responders relapsed. A patient in group A
      with increased serum ALT concentration but negative HCV-RNA at the end of
      treatment became a full responder after six months. Of nonresponders to 3 MU
      interferon alpha2b every two days for three months, 20% responded to higher
      interferon doses, but none to continued standard dose. Prolonged treatment with
      interferon may be necessary to obtain a sustained response. However, treatment
      with higher-dose interferon was not tolerated in 20% of the patients.

PMID- 9011467
TI  - Short-term versus sustained response to interferon therapy: effect on histology.
AB  - In order to evaluate the histological treatment response in patients with chronic
      hepatitis C virus (HCV) infection, different histological scoring systems have
      been developed. The scoring systems provide means of statistically comparing
      histopathological parameters in serial liver biopsies and have thus become
      important requirements of therapeutic trials. Patients with biochemical and
      virological responses to interferon (IFN) also improve histologically during
      treatment. However, after treatment cessation, many patients will have a
      biochemical/virological relapse. These short-term responders also relapse
      histologically, thus limiting the long-term benefit of a single treatment course,
      although, repeated courses of IFN in short-term responders may retard
      histological deterioration. In contrast, sustained biochemical/virological
      responders seem to have a durable histological response with a continuous and
      gradual improvement of all necroinflammatory parameters and fibrosis
      posttreatment.

PMID- 9011469
TI  - Managing patients on interferon therapy.
AB  - Interferon (IFN) has become the standard therapy for chronic hepatitis C. The use
      of IFN should be accompanied by adequate diagnosis and management using standard
      practices as well as new and sophisticated techniques now available. A liver
      biopsy performed prior to IFN therapy initiation remains the standard for
      adequate histological diagnosis of HCV disease as well as determination of
      disease severity and the presence of liver cirrhosis. ALT normalization is not
      adequate to determine complete short-term response to IFN treatment. Adverse
      effects resulting from IFN therapy include a flulike syndrome, hematologic
      effects, neuropsychiatric effects, and thyroid abnormalities. The majority of
      these can be adequately managed without discontinuation of IFN treatment.
      However, preexisting psychiatric conditions are a contraindication to IFN
      therapy. IFN treatment also is contraindicated in patients with autoimmune
      hepatitis (AIH). Therefore, it is important to distinguish AIH from chronic HCV
      infection using HCV-RNA analysis and determination of autoimmune titers
      (including anti-LKM antibodies, anti-SMA, and ANA). Recently reported adverse
      effects of IFN include respiratory and ocular effects. Serological diagnosis of
      HCV infection has evolved to the use of second- and third-generation ELISA tests.
      Although sophisticated, these tests cannot distinguish between active and
      quiescent infection, and therefore are of limited value in monitoring treatment
      response. Several other techniques have been suggested: the ratio between IgG and
      IgM class anti-HCV core antibodies, detection of antibodies against a
      glycosylated recombinant product of the E2 envelope glycoprotein, and several
      different polymerase chain reaction (PCR) techniques. The latter appears to be
      the most promising. Use of these techniques should be incorporated into the
      monitoring of IFN therapy to assist in the evaluation of adequate treatment
      response, the need for treatment alteration, and estimation of relapse risk upon
      treatment cessation.

PMID- 9011468
TI  - Predictors of response to interferon therapy.
AB  - An optimal treatment schedule is the first factor that influences sustained
      responses to interferon (IFN) therapy. There is growing evidence that prolonged
      IFN therapy (at least 12 months or longer) increases the sustained response rate.
      A low viremia at baseline favorably affects the long-term response to IFN. High
      viral replication does not preclude response, but highly viremic patients tend
      not to sustain their response. Patients with genotypes 2 and 3 (Simmonds
      classification) have an improved likelihood of responding compared to patients
      with genotype 1; unfortunately, genotype 1 predominates in Western countries. The
      "quasispecies" diversity of hepatitis C virus (HCV) may play a role in
      determining response to IFN, which is more likely in patients with lesser degrees
      of HCV diversity. However, studying the nucleotide diversity of the hypervariable
      region 1 of HCV is a very complex and expensive process that cannot be applied to
      a large number of patients. The sustained response rate is higher in patients
      with mild disease than in cirrhotic patients. Cirrhotics should be treated with
      caution, since IFN therapy could induce serious side effects and decompensation.
      Baseline predictive factors of response are useful to improve the cost-benefit
      ratio of IFN therapy but cannot be considered inclusion/exclusion criteria. The
      decision on how to treat should be based upon the individual characteristics of
      each patient.

PMID- 9011470
TI  - Interferon-alpha therapy for chronic hepatitis C in special patient populations.
AB  - Interferon-alpha therapy for chronic hepatitis C in special patient populations
      raises a number of issues. Patients with hemophilia, kidney disease requiring
      hemodialysis, mixed cryoglobulinemia, HIV infection, and those receiving an
      allograft share some characteristics that complicate the treatment of hepatitis C
      virus infections. These patients generally have some degree of immune deficiency,
      higher levels of hepatitis C virus replication, and are infected with genotypes
      1a or 1b. Each of these characteristics is often associated with a poor response
      to interferon therapy. Clinical research in this area also has been limited.
      Current data and clinical experience demonstrate that interferon-alpha therapy
      should be considered in patients with hemophilia who have concurrent hepatitis C
      viral infection. Other hepatitis C virus-infected patient populations in which
      interferon-alpha therapy may be beneficial include those undergoing hemodialysis,
      mixed cryoglobulinemia, or HIV infection. Further, the high incidence of relapse
      following treatment cessation in these patients warrants prolonged administration
      of interferon-alpha. Patients undergoing renal or hepatic allograft
      transplantation who develop hepatitis C virus infections are not as likely to
      benefit from interferon-alpha therapy. These patients may be at risk for
      allograft rejection during interferon treatment.

PMID- 9011471
TI  - Interferon-ribavirin combination therapy for chronic hepatitis C.
AB  - Following preliminary reports of small studies that suggested a clinically
      important enhanced benefit from combination therapy with interferon-alpha (IFN)
      and ribavirin over IFN monotherapy in chronic hepatitis C, a meta-analysis of
      data from these studies was performed to estimate the efficacy and tolerability
      of combination therapy in chronic hepatitis C. Records were obtained from 59
      patients who had received combination therapy with IFN 3 MU three times weekly
      and ribavirin 1000-1200 mg daily for six months and were followed for six months
      after stopping combination therapy. Outcome measures included the percentage of
      patients showing ALT normalization and HCV-RNA negativity six months after
      therapy (sustained response) and the percentage of patients stopping therapy
      because of side effects. Sustained response was observed in 21% of IFN
      nonresponders and in 60% of patients who had relapsed after IFN. For naive
      patients, the estimated sustained response rate was 52%; the observed response
      rate was 46%. No serious adverse effects were noted; less than 10% of patients
      discontinued study medication. This meta-analysis of IFN-ribavirin combination
      therapy for chronic hepatitis C suggests that combination therapy results in a
      two- to threefold greater efficacy than IFN monotherapy, whereas side effects are
      similar to IFN monotherapy, with the exception of ribavirin-induced anemia.
      Interferon-ribavirin combination therapy might become the next step in antiviral
      therapy for chronic hepatitis C.

PMID- 9011472
TI  - Magnitude and management of HCV infection in France.
AB  - The prevalence of hepatitis C virus infection in the general population in France
      averages 1%. The majority of these patients are viremic with detectable HCV-RNA.
      Further, 75% of these individuals did not suspect they were at risk for being HCV
      carriers. Less than 10% of HCV carriers in France have been identified and even
      fewer have been treated with interferon. In addition to infection following
      intravenous drug use, preliminary studies suggest that most newly infected
      patients have become infected following surgery or endoscopy without transfusion.
      A large serological study of patients scheduled for surgery identified 4% HCV
      carriers. Other studies have determined that more than 8% of patients who
      received prior transfusions are now anti-HCV positive. These findings prompted
      the French government to initiate a screening program in France to identify
      patients at risk for HCV infection. This national program also involves the
      establishment of regional HCV reference centers to coordinate efforts among
      hospitals, gastroenterology/hepatology specialists, and general practitioners.
      The mission of the program is to promote screening and disseminate appropriate
      clinical practice guidelines for the management of HCV infection. The goal is to
      identify infected patients and initiate optimal interferon therapy as early as
      possible in the course of HCV infection to prevent the long-term complications
      secondary to infection.

PMID- 9011474
TI  - Hepatitis C virus: a historical perspective.
AB  - Identification and diagnosis of the infecting agent responsible for hepatitis C
      have only recently occurred. Recognition of an infecting agent distinct from that
      resulting in hepatitis A or B was made approximately 50 years ago. However, the
      ability to screen and detect this agent was possible only after molecular biology
      studies which led to the cloning of parts of the hepatitis C virus (HCV) and the
      development of a diagnostic antibody test reported by Michael Houghton and
      colleagues in 1989. The discovery and cloning of HCV has led to a greater
      understanding of its relationship to acute and chronic hepatitis, cirrhosis,
      primary liver cancer, and extrahepatic conditions including essential
      cryoglobulinemia, glomerulonephritis, and serum autoantibody positivity. New
      antibody tests and quantitation of HCV-RNA have allowed better diagnosis of
      infectivity and monitoring of treatment effects. HCV genotypes are being related
      to the natural history of the disease and the effects of treatment. Research
      continues on HCV hepatitis and other newly identified viral hepatitis agents.

PMID- 9011475
TI  - Patterns of progression: unpredictability and risk of decompensated cirrhosis.
AB  - Hepatitis C virus (HCV) infection appears to have a slow but progressive
      evolution to chronic hepatitis and cirrhosis in a significant percentage of
      patients. Chronic hepatitis develops in 60-80% of patients. Worldwide prospective
      studies have shown that a further 20-30% of patients with chronic active
      hepatitis will develop cirrhosis regardless of the possible source of HCV
      infection. The percentage of cirrhotics is generally believed to increase
      progressively as the length of follow-up increases. In patients with chronic HCV,
      there also is high risk for the development of hepatocellular carcinoma. Factors
      influencing the rate of progression from chronic hepatitis to cirrhosis appear to
      include age at time of exposure, duration of infection, degree of liver damage at
      initial biopsy, immunological status, and possibly HCV genotype. The mean
      intervals between the time of initial infection and the diagnosis of chronic
      hepatitis, cirrhosis, and hepatocellular carcinoma have been estimated to be 10,
      20, and 30 years, respectively. The progression of disease is variable and is not
      always orderly and sequential. Patients can progress from chronic persistent
      hepatitis or chronic active hepatitis directly to hepatocellular carcinoma
      without first developing cirrhosis, especially those with genotype 1b. In
      addition, cirrhosis does not appear to lead to clinically apparent hepatic
      failure in all patients. Because of the variability in the clinical presentation
      and clinical progression of chronic HCV, long-term follow-up studies may be
      necessary to fully assess the sequelae of chronic HCV infection. Most patients
      with chronic HCV have abnormal liver histology but can present as otherwise
      healthy individuals. In contrast, patients with chronic HCV who have normal
      hepatic chemistries can have substantial hepatocellular damage. Consequently,
      treatment at diagnosis offers the greatest likelihood of eliminating the virus
      and preventing progression to more severe liver disease.

PMID- 9011476
TI  - Risk factors and prevention of hepatocellular carcinoma in HCV infection.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors
      worldwide. Several risk factors for HCC development have been identified,
      including cirrhosis, hepatitis B virus (HBV) infection, and hepatitis C virus
      (HCV) infection. With regard to cirrhosis, multivariate analysis indicates that
      alcohol abuse, HBsAg positivity, and anti-HCV seropositivity are independent
      variables associated with an increased risk for HCC in the cirrhotic patient. A
      close relationship between chronic HBV infection and HCC has been established by
      epidemiological studies and laboratory investigations. Evidence indicates that
      HCV also plays a leading role in development of HCC. Most patients with HCV
      related HCC develop the tumor as a consequence of long-standing infection
      accompanied by chronic and progressive liver damage. In our study of 290
      consecutive patients with cirrhosis, patients with persistently elevated or
      fluctuating ALT levels had a significantly greater rate of HCC development. The
      mechanism of HCC development in HCV infection remains to be elucidated. The
      annual cumulative risk of developing HCC is approximately 1% in patients without
      cirrhosis at inclusion and 3-10% in those with cirrhosis, depending on the stage
      of cirrhosis and presence of etiological cofactors. Although some evidence
      suggests that patients infected with the HCV genotype 1b are at increased risk
      for development of more severe liver disease, including HCC, results of our
      prospective study do not support a difference between cirrhotic and noncirrhotic
      patients in terms of the natural course of cirrhosis and the rate of developing
      HCC based on genotype. Strategies to prevent HCV-related HCC include blood
      screening and treatment of chronic HCV infection with interferon-alpha. Recent
      studies suggest that interferon-alpha treatment may prevent the development of
      HCC in HCV infection. Further research is warranted.

PMID- 9011477
TI  - Modeling therapeutic benefit in the midst of uncertainty: therapy for hepatitis
      C.
AB  - Randomized, double-blind, controlled clinical trials are the gold standard for
      medical therapy. When a disease is rare or slowly progressive over many years,
      such a trial may not be feasible. Decision analysis provides a bridge between
      current studies with short-term surrogate markers and a large, longitudinal
      clinical trial. With decision analysis, results of current studies can be
      summarized and the outcome of a long-term study projected under explicit
      assumptions. Chronic hepatitis C is a disease that is slowly progressive, and the
      requirements of a longitudinal clinical study could be prohibitive. Therefore, we
      review the basic steps of decision analysis, apply these steps to two recent
      decision analyses evaluating the use of interferon-alpha2b (IFN) in the treatment
      of chronic hepatitis C, and discuss possible implications of decision modeling
      for this disease. The estimated marginal cost per year of life gained from IFN
      therapy ranged from approximately $3000 to $55,000 in these two studies. The wide
      range is based on different estimates of treatment costs and disease progression.
      This analysis has identified gaps in the current knowledge regarding the natural
      progression of hepatitis C and has established criteria to evaluate new
      developments and their impact on chronic hepatitis C.

PMID- 9011473
TI  - Mode of hepatitis C virus infection, epidemiology, and chronicity rate in the
      general population and risk groups.
AB  - Since the discovery of the hepatitis C virus (HCV), it has become evident that
      this infectious agent is a primary cause of posttransfusion and sporadic non-A,
      non-B hepatitis. Identification and introduction of surrogate markers for
      posttransfusion hepatitis and later introduction of anti-HCV screening has
      decreased the incidence of posttransfusion hepatitis. Community-acquired HCV
      infection is less common than posttransfusion HCV hepatitis. HCV infection may
      lead to liver cirrhosis without prior evidence of laboratory or histologic
      infection. Populations at risk for HCV infection include patients receiving organ
      transplants, health care workers, infants born to HCV-infected mothers, and
      hemodialysis patients. Intravenous drug abusers and their sexual partners also
      demonstrate a high rate of HCV infection. Nosocomial HCV transmission may occur
      despite the observance of universal precautions. Dental or surgical intervention,
      salivary inoculation, family members infected with HCV, cocaine abuse, HIV
      infection, and lower socioeconomic status also each correlate with an increased
      risk of infection. HCV infection is associated with many immune-mediated
      diseases. There may also be some relationship between human leukocyte antigens
      and HCV infection. Since there currently is no HCV vaccine, prevention of
      exposure remains the only possibility for reducing HCV transmission and
      prevalence.

PMID- 9011480
TI  - Health assessment for chronic HCV infection: results of quality of life.
AB  - The perception that chronic hepatitis C is an asymptomatic disease contrasts with
      many studies that show a strong association between chronic hepatitis C,
      hepatocellular cancer, and fatal liver disease. In order to resolve these issues,
      it is logical to directly evaluate the quality of life in patients with chronic
      hepatitis C and to compare this to the normal population as well as cohorts of
      patients with other chronic diseases. The Sickness Impact Profile was used to
      evaluate the impact of disease and interferon therapy on health-related quality
      of life in patients with chronic hepatitis C. Using this tool, patients with
      chronic hepatitis C had a total Sickness Impact Profile score of 9.0, compared
      with a score of 3.6 among the general population (P < 0.05). Patients with
      chronic hepatitis C also had significantly worse scores in almost every category
      of the Sickness Impact Profile that could be compared. However, statistically
      significant differences were observed only at the 24-week evaluation for work and
      at the end-point evaluation for the sleep and rest and recreation and pastimes
      categories. A more sophisticated instrument, based on the Medical Outcomes Study
      36-item short-form health survey, found that patients with chronic hepatitis C
      scored significantly lower (P < 0.01) than the general population on each of the
      subscales in this survey. In addition, they scored significantly lower than
      patients with hypertension in seven of the subscales and two additional generic
      scales. Patients with chronic hepatitis C were most comparable to those with type
      II diabetes. A larger, more comprehensive study is underway to further evaluate
      these relationships.

PMID- 9011478
TI  - Hepatitis C virus: molecular biology and genetic variability.
AB  - The pathogenetic mechanisms of hepatitis C virus (HCV) infection are poorly
      known. An understanding of HCV biology and the potential clinical impact of HCV
      genetic variability is essential to managing, treating, and preventing HCV
      infections. HCV is a member of the Flaviviridae viral family. Its genome is a
      positive, single-strand RNA molecule. The structure of the HCV particles is
      poorly known due to the lack of an efficient cell culture system as well as a
      striking heterogeneity in density. The core protein may have a regulatory role on
      both viral and cellular gene expression. The mechanisms of HCV-RNA replication
      may include synthesis of negative strand intermediates, which drive synthesis of
      new positive RNA genomes. New procedures have been developed to better identify
      and characterize the HCV-RNA genome. The mechanisms of HCV persistence are
      currently unknown, although it is known that HCV chronicity develops despite
      humoral and cellular responses to HCV proteins. HCV-RNA shows significant genetic
      variability with an estimated rate of nucleotide change of approximately 10(-3)
      substitutions/site/year. Currently, three major HCV genotypes and three to seven
      minor subtypes can be distinguished. The geographical distribution of these
      genotypes and subtypes varies significantly. It appears that poor clinical
      response to interferon (IFN) is more common with HCV genotype 1. In addition,
      some studies have shown an association between chronic infection, severe chronic
      hepatitis, and cirrhosis with subtype 1b. Further, there is evidence for a
      potential direct effect of HCV in liver carcinogenesis, with subtype 1b possibly
      being an independent risk factor for hepatic carcinoma development. HCV-RNA
      circulates as a population of RNA molecules, which creates a heterogeneity
      referred to as "quasispecies." It is possible that some HCV strains might have
      direct clinical implications. It may be that highly heterogeneous populations
      observed prior to treatment might correlate with a lower rate of response to IFN
      therapy.

PMID- 9011479
TI  - Nonhepatic manifestations and combined diseases in HCV infection.
AB  - Infection with hepatitis C virus (HCV) may affect not only the liver but also
      various nonhepatic tissues and organs and may combine with many etiologically
      unrelated diseases and morbid conditions. Numerous nonhepatic manifestations in
      HCV infection have been previously reported. For some (eg, cryoglobulinemia), the
      association is well established. For others, such as sialadenitis and lichen
      planus, the association is probable (but not completely documented) and, for the
      remainder, the associations are weak. Extrahepatic manifestations may result from
      immunological mechanisms as well as virus invasion and replication in the
      affected extrahepatic tissues and organs. Thyroid abnormalities, primarily
      Hashimoto's disease, and isolated increases of anti-thyroid antibodies (ATPO)
      appear to be more frequent in chronic hepatitis C than B or D, with high ATPO
      titers clustering mainly among females. Interferon-alpha (IFN-alpha) therapy is
      associated with development of thyroid dysfunction in 5.5-12.9% of patients,
      usually exposing preexisting subclinical thyroid abnormalities. Mixed
      cryoglobulinemia (MC) is commonly found (36-45%) in patients with chronic HCV
      infection; however, only in a minority of cases does it become clinically
      manifested as systemic vasculitis with purpura, neuropathy, or Raynaud's
      phenomenon. In a number of patients, MC may terminate in non-Hodgkin's B-cell
      lymphoma. Treatment of these lymphoproliferative disorders with IFN-alpha is
      advocated. Idiopathic thrombocytopenia is now recognized more frequently in
      association with chronic HCV infection and is usually aggravated by IFN-alpha
      therapy. Patients with porphyria cutanea tarda (PCT) have demonstrated
      serological markers of HCV infection in 62-82% of cases. The usefulness of IFN
      alpha in PCT remains to be demonstrated. Lichen planus has also been found in
      association with chronic HCV infection, particularly when severe or affecting the
      oral cavity. Other nonhepatic manifestations have also been reported in HCV
      infection such as diabetes, corneal ulceration, uveitis, and sialadenitis. These
      manifestations deserve further study and documentation. Finally, markers of
      autoimmunity occur with high frequency in chronic HCV infection; however,
      combination with the classical syndrome of autoimmune hepatitis is rare. In the
      presence of various autoantibodies, the clinical features of chronic hepatitis C
      do not appear to be modified and, contrary to general perception, IFN-alpha
      therapy within randomized controlled trials should not be withheld since the
      response rate to IFN-alpha does not appear to differ in the presence or absence
      of low titers of these markers.

PMID- 9011481
TI  - High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C:
      a pilot study.
AB  - Acute hepatitis C takes a chronic course in 50-80% of cases. Results with
      interferon treatment are conflicting. To evaluate the efficacy of high-dose
      interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon
      alpha2b administered subcutaneously daily until normalization of serum
      transaminase concentrations. Treatment was begun when a diagnosis of acute
      hepatitis C was established. HCV-RNA was tested using PCR prior to treatment,
      three times weekly during the first two weeks of treatment, and then once weekly
      until the end of therapy. During the 15-month follow-up, HCV-RNA tests were
      performed monthly up to month 6 and every two to three months thereafter. Twenty
      four patients were enrolled at the time of writing; age ranged from 18 to 76
      years (mean = 32), and nine patients were men. All patients presented with
      cholestatic hepatitis; 19 were actively abusing intravenous drugs, four had no
      known parenteral exposure, and one was a medical laboratory technician. All
      patients were anti-HCV positive, HCV-RNA positive, and HIV negative. Five
      patients were infected with genotype 3, five with genotype 1a, five with genotype
      1b, three with genotypes 3 and 2, and one with genotypes 1 and 2. All patients
      exhibited normalized serum transaminase concentrations within 18-43 days; HCV-RNA
      became negative in all patients within 4-12 days. Toxicity did not exceed grade 1
      and disappeared within three days of treatment. In the follow-up period, which
      ranged from six to 29 months (mean = 19.5 +/- 10.4), serum ALT concentrations
      remained normal and HCV-RNA remained negative in all patients except two dropouts
      and two patients who developed relapsing disease after having been HCV-RNA
      negative for three and eight months, respectively. In both patients, the same HCV
      genotype 3 reemerged. Serum ALT concentrations ranged from 531 to 1940 IU/liter
      (mean = 1055; normal < 22). Concentrations of HCV-RNA (Quantiplex; Chiron,
      Emeryville, California) were < 3.5 x 10(5) eq/ml in nine of 14 PCR-positive
      patients. In the other five patients, concentrations ranged from 10.4 x 10(5)
      eq/ml to 131.6 x 10(5) eq/ml (mean = 69.6 x 10(5)). No correlation was observed
      between HCV-RNA concentrations and serum ALT concentrations at presentation (r =
      0.331; P = 0.67) and total dose of interferon-alpha2b administered until
      normalization of ALT (r = -0.088; P = 0.74). Twenty-two of 24 patients completed
      treatment (two were noncompliant). Of these, 20 achieved a complete response (HCV
      RNA negative for at least six months). Two of these patients relapsed, and 18
      (90%) remained HCV-RNA negative for 18.65 (+/-9.7) months. These findings suggest
      that high-dose interferon-alpha2b is well tolerated and effective in preventing a
      chronic course of hepatitis C infection.

PMID- 9011482
TI  - Duration of HCV infection as a predictor of nonresponse to interferon.
AB  - Duration of hepatitis C virus (HCV) infection is a key feature in determining
      responsiveness to interferon (IFN). Studies assessing its value as a predictive
      factor in chronic HCV infection show that a long duration of infection reduces
      the likelihood of a sustained response to IFN (defined as ALT normalization and
      clearance of serum HCV-RNA). The effect of HCV infection duration is independent
      of the presence of cirrhosis and level of HCV viremia. Meta-analysis of IFN
      trials in acute HCV infection shows an obvious effect of the drug on long-term
      ALT normalization and HCV-RNA clearance. Treatment of HCV infection during the
      acute or early chronic phase could therefore maximize therapeutic effectiveness.

PMID- 9011483
TI  - Two years versus six months of interferon therapy for chronic hepatitis C.
AB  - Short-term (end-of-treatment) responses (ETR) to interferon (IFN) therapy for
      chronic hepatitis C are encouraging; however, the relapse rate is high, and long
      term response is obtained in only 12-25% of patients. The Australian Hepatitis C
      Study Group conducted a trial of 230 patients that compared the standard 3 MU
      three times a week six-month course of IFN-alpha2b with 5 MU three times a week
      for six months (5 MU group) or 3 MU three times a week for two years (two-year
      group). ETR (normalization of serum aminotransferase level until the end of
      treatment) rates based on an intent-to-treat analysis were 64% for the 5 MU group
      and 58% for the combined 3 MU groups. After six months of treatment, the overall
      relapse rate was 71%, and the long-term response (LTR; continued normal
      aminotransferase until six month follow up) rate did not differ significantly
      between the 3 MU (17% of all treated, 27% ETR) and 5 MU groups (20% of all
      treated, 31% ETR). In contrast, among the 46 patients who exhibited an ETR in the
      two-year group, 27 (59%) had a LTR to IFN, resulting in an overall LTR rate of
      33% for all patients treated for up to two years (P < 0.001 compared with 3 MU
      group). Among these 46 subjects, 11 did not complete the full two-year course,
      including eight who withdrew due to adverse effects. Nine of these 11 patients
      had received at least 12 months of therapy. All 18 LTR subjects tested
      (irrespective of treatment group) were serum HCV-RNA negative at the 12-month
      follow-up evaluation. Improvement in hepatic inflammation was significantly
      greater among those treated for two years compared with six months, but there was
      no reduction in fibrosis score in any group. Among the entire study group,
      treatment duration, liver histology, and liver function (assessed by antipyrine
      clearance test) were the only independent predictors of ETR, although HCV
      genotype was closely related to histological severity (eg, cirrhosis was present
      in 60% of type 1 and 18% of type 3). Viral load and duration of infection were
      additional predictors of LTR; however, there were insufficient data to determine
      whether prolonging treatment beyond six months overcomes the negative impact of
      these predictors. Continuing IFN therapy for at least 12 months decreases the
      relapse rate by 50% and thereby improves the LTR rate compared with a six-month
      treatment course. However, our experience of 24 months of treatment indicates
      that initial IFN treatment courses of this duration are not well tolerated by
      approximately 20% (8/46) of patients and are unlikely to improve the results
      obtained with 12-18 months of treatment.

PMID- 9011484
TI  - Treatment of chronic hepatitis C by interferon for longer duration than six
      months.
AB  - The efficacy of various regimens using interferon-alpha (IFN-alpha) in the
      treatment of hepatitis C virus (HCV) infection was analyzed in a meta-analysis of
      33 randomized clinical trials (RCTs). The results of the meta-analysis showed
      increased complete and sustained ALT response rates in patients receiving IFN 3
      MU three times a week for six months compared with patients receiving placebo or
      no treatment. The dose effect (6 MU three times a week versus 3 MU three times a
      week) on complete ALT response rate at the end of treatment was significant, with
      a mean 10% improvement at both six and 12 months. There also was a significant
      dose effect on sustained response for 12 months treatment, with a mean 17%
      improvement. There was a significant treatment duration effect on sustained
      response rate at 3 MU three times a week and 6 MU three times a week, with a mean
      improvement of 16% (> or = 12 months vs six months) with 3 MU three times a week.
      Due to adverse events, we conclude that the best efficacy-risk ratio favors IFN
      treatment with 3 MU three times a week for at least 12 months. The results of our
      RCT comparing three IFN regimens showed that patients receiving 3 MU three times
      a week for up to 18 months exhibited significant improvements in histological
      activity score, normalization of serum ALT concentrations, and sustained response
      compared with patients receiving a lower dose or shorter duration of treatment
      with IFN. Together, these results support the conduct of another RCT to evaluate
      the hypothesis that long-term, continuous IFN treatment may significantly reduce
      the incidence of cirrhosis in patients with HCV infection.

PMID- 9011485
TI  - [Therapy of endemic goiter with iodide or l-thyroxine in older patients].
AB  - OBJECTIVE: To compare the efficacy of iodide (300 micrograms daily) with that of
      levothyroxine (1.5 micrograms/kg daily) in the treatment of endemic goitre in
      middle-aged and elderly persons. The possible occurrence of antibodies against
      thyroid peroxidase and thyroglobulin was also tested. PATIENTS AND METHODS: 67
      patients (54 women, 13 men; aged over 40 years, average 53.5 years) with endemic
      goitre, excluding toxic goitre, were randomly treated with either iodine or
      thyroxine. Every 3 months for one year their thyroid volume was obtained by
      ultrasound and the activities of thyroid hormone (TH) and thyroid stimulating
      hormone (TSH) and the concentration of antibodies against peroxidase and
      thyroglobulin were measured. RESULTS: In patients on levothyroxine the thyroid
      volume had already markedly decreased after 3 months (P < 0.0001), diminishing by
      15.4% at 12 months. Volume reduction in the group on iodine was 16.2% at one
      year. There was no significant difference between the two medications and no case
      of antibody production in the iodine group. CONCLUSIONS: Treatment of endemic
      goitre with iodine alone is efficacious even in middle-aged or elderly patients,
      toxic goitre having been excluded. There was no evidence of antibody production
      against thyroid antigens at the stated iodine dosage.

PMID- 9011486
TI  - [The effect of lumbar relief orthoses with abdominal compression on esophago
      gastrointestinal motility].
AB  - OBJECTIVE: To investigate the effect of lumbar ortheses with abdominal
      compression on gastro-oesophageal reflux and gastrointestinal transit. PATIENTS
      AND METHODS: In a prospective study 20 consecutive patients with lumbar syndrome
      treated with lumbar orthesis (10 female, 10 male, median age 54.6 years) were
      investigated for gastro-oesophageal reflux, mouth-to-cecum transit time (MCT),
      and whole-gut transit time. Gastro-oesophageal reflux was assessed performing an
      ambulatory pH metering of the distal oesophagus over a period of 10 h with and
      without ortheses on two separate study days. After positioning of the pH catheter
      patients ingested a liquid-solid test meal labelled with 10 g lactulose and 750 g
      indigocarmine to determine MCT with the hydrogen breath test and whole-gut
      transit by the first appearance of indigocarmine in the stool. Dyspepsia was
      assessed by using a standardized questionnaire. RESULTS: Lumbar ortheses induced
      a significant increase in reflux time (pH < 4) (8.1 vs 4.1%), total number of
      reflux episodes (102.5 vs 69.5) and duration of longest reflux episode (6.0 vs
      3.7 min) (P < 0.05). 12 patients with ortheses revealed an increase in relative
      reflux time (2.1-24.5%, median: 8.2%) more than two standard deviations compared
      to previously obtained normal values. In these patients during ortheses dyspeptic
      symptoms correlated significantly with reflux time (r = 0.6; P < 0.05). In
      contrast, MCT and whole-gut transit time in patients with and without ortheses
      did not differ significantly (85 vs 85 min; 10.2 vs 9.6 h). CONCLUSION: Lumbar
      ortheses with abdominal compression, nowadays frequently used in the lumbar
      syndrome, produce gastro-oesophageal reflux associated with dyspepsia.
      Gastrointestinal transit time is not affected, though.

PMID- 9011487
TI  - [Intravascular ultrasound for monitoring percutaneous fenestration of a membrane
      from an aortic dissection].
AB  - HISTORY AND CLINICAL FINDINGS: A 51-year-old man, having experienced sudden
      retrosternal pain was admitted to another hospital with suspected myocardial
      infarction. He also had dysaesthesia and later paresis of the left leg. There was
      no sign of acute infarction in the ECG. However, computed tomography revealed
      aortic dissection, type III (DeBakey). The left pedal pulses were diminished. The
      patient was transferred to our hospital for further diagnosis and treatment. At a
      blood pressure of 110/60 mm Hg the occlusion pressure of the leg artery was 55 mm
      Hg on the left and 95 mm Hg on the right. INVESTIGATIONS: Transoesophageal
      echocardiography detected no abnormality of the aortic valve and ascending aorta.
      But distal to the origin of the left subclavian artery it demonstrated a free
      floating membrane of an aortic dissection and computed tomography showed its
      extension to the aortic bifurcation. TREATMENT AND COURSE: At first, because of
      the incomplete ischaemia syndrome affecting the left leg, a percutaneous
      fenestration of the dissection membrane was performed. After conventional
      angiography intravascular ultrasound imaging was also undertaken; it revealed
      that the membrane was almost completely occluding the left iliac artery. Under
      ultrasound monitoring a puncture needle and two balloon catheters were introduced
      across the membrane and thus a window created in it. The clinical findings
      quickly disappeared and the patient was discharged without further operation.
      CONCLUSION: Monitoring with intravascular ultrasound imaging makes it possible to
      perform safely a percutaneous fenestration of the membrane of an aortic
      dissection and to obtain immediate evidence of its success.

PMID- 9011488
TI  - [Systemic therapy of psoriasis].

PMID- 9011489
TI  - [Diagnosis of infections with Legionella species].

PMID- 9011490
TI  - [Nobel Prize for medicine 1996].

PMID- 9011491
TI  - [Oral anticoagulation in activated protein C resistance?].

PMID- 9011493
TI  - [Heterotopic ossification of a dacron prosthesis in peripheral arterial occlusive
      disease].

PMID- 9011492
TI  - [Serum lipid determination after acute myocardial infarction].

PMID- 9011494
TI  - [Embryo transfer in the goat--a review].
AB  - The available techniques for the control of the estrous cycle and superovulation
      in goats are covered. Most commonly the estrous cycle is controlled by means of
      progestagen pessaries or s.c. implants. To superovulate goats, FSH is more
      suitable than PMSG. As an alternative, goats may be immunized against inhibin.
      Premature regression of corpora lutea is a common complication in superovulated
      goats. Collection and transfer of embryos is usually accomplished via laparotomy.
      Occasionally endoscopic techniques are utilized. A recently invented technique
      for transcervical embryo collection is touched upon. Methods of in vitro culture
      and preservation of embryos resemble those commonly applied in cattle.
      Satisfactory success rates are achieved with the transfer of frozen-thawed
      blastocysts. Vitrification of goat embryos is feasible. There are reports on
      successful splitting and fusion (chimaera formation) of goat embryos and on in
      vitro fertilization (IVF). The goat may serve as a suitable model for the
      invention of new approaches in biotechnology in ruminants.

PMID- 9011495
TI  - [The use of biotechnology in animal breeding].
AB  - Biotechnological techniques are extensively used in dairy breeding programs.
      Thus, artificial insemination and embryo transfer (and associated techniques)
      constitute an integral part of modern breeding programs. In pig breeding, embryo
      transfer is mostly restricted to special problem areas because of its high costs.
      Currently this technique is used for the exchange of genetic material on an
      international level, for the creation of specific pathogene free herds, and in
      connection with cryoconservation for the setup of embryobanks in the context of
      the preservation of genetic resources.

PMID- 9011497
TI  - [Status of development and areas of employment of in vitro production of cattle
      embryos].
AB  - Efficient methods for the collection of oocytes derived from slaughterhouse
      ovaries and living animals are available. Maturation, fertilization and culture
      of bovine oocytes/embryos can be performed in vitro with high success rates. The
      in vitro culture from the fertilized oocyte up to the blastocyst stage currently
      is the most limiting step of the whole procedure. The establishment of a
      completely defined culture system would allow the identification of the
      physiological requirements for preimplantation embryo development and the
      stepwise improvement of the in vitro production system. The physiological
      integrity of in vitro produced embryos compared to their in vivo counterparts can
      be assessed either by molecular biological techniques or in metabolism studies.
      The in vitro production of bovine embryos with its variety of areas of
      applications is a useful tool in maintenance and improvement of competitiveness
      of future cattle breeding.

PMID- 9011498
TI  - [Experiences in the changes of biotechnology in veterinary practice].
AB  - The transmission of old methods and the transformation of new knowledge in to
      animal breeding practice has an cultural tradition lasting millenniums. Each
      epoch had its own strategy of solving problems because progress is independent of
      religions and ideologies, and therefore, it can not be hindered. In the past
      different biotechnologies have increased progress in animal breeding
      exponentially, and it can be supposed that the course of the exponential curve
      will not change in the foreseeable future. Anyone who intends to compete
      internationally is compelled to use the new technologies, wherever old methods
      can not longer compete. The transition to the new biotechnology especially in
      Germany, hits limitations an two levels: on the one hand, an exaggerated desire
      for safety that has created the German gene law and, on the other hand the animal
      breeding industry that can hardly afford the expensive biotechnology because of
      its economic condition. It seems advisable to revise both the gene law and the
      expense of the technology. Animal breeding research should foster simplification
      (make less expensive) of biotechnology, and politicians should ask weather it is
      necessary for the gene sector to migrate further abroad. In animal breeding, the
      gene transfer is practical (e.g., liposome mediated gene transfer via sperm
      cells) because of its low costs, and so it is absurd not to allow its use. In
      Germany, transgenic individuals have to bee discarded at the knackery, whereas in
      the Netherlands heifers derived from the bull HERMAN, that is transgenic for
      lactoferrin are allowed to calf (and produce milk). Currently, gene transfer is
      not a viable alternative because of the negative emotional impact of
      biotechnology. Only someone who uses this technique may be responsible for
      handling and creating it without having, therefore, to overstep ethical borders.

PMID- 9011496
TI  - [Optimization of embryo production in cattle by aspiration of the fluid from
      large follicles before induction of superovulation with the assistance of an
      ovary puncture cannula].
AB  - During a field study at the Besamungsverein Neustadt a.d. Aisch rectal palpable
      large follicles were eliminated in 167 selected donor cows prior to
      superovulation induction. For this purpose a so-called "Ovarpunktionskanule" was
      used, which allows after vaginal introduction the aspiration of follicle fluid
      from a rectal fixed ovary. From 152 flushed donor cows an average of 11.0 viable
      embryos was recovered. Using fresh semen from one problem bull for insemination
      of donors 13.2 viable embryos per flushing were collected in relation to 4.1
      using frozen semen. At the same time the rate of unfertilized ova dropped from
      9.8 to 3.5. The follicle aspiration with a so-called "Ovarpunktionskanule" prior
      to superovulation induction is-from a practical viewpoint-superior to the
      dominant follicle removing with the help of transrectal ultrasonography.

PMID- 9011499
TI  - [Molecular biological aspects of animal production].
AB  - Molecular biological methods developed for basic research have been increasingly
      employed in animal production. For example, individual animals can be identified
      by their unique DNA sequences in DNA fingerprints and their genetic relationships
      can be established by more detailed sequence comparisons. It is also possible to
      diagnose gene defects and to determine the sex of preimplantation embryos. This
      information can then be used as the basis for an efficient breeding program.
      Methods for the analysis of RNA yield information about genetic or environmental
      factors which influence the expression of specific genes for example genes of
      economic value in milk production or genes which are important for
      preimplantation embryo development. This information will enable further
      improvements in embryo transfer and associated biotechniques which promise to
      improve the rate of genetic improvement (NIEMANN and MEINECKE, 1993). In the
      following section, we will briefly describe these molecular biological methods
      and their applications in animal breeding using examples from current research in
      our research group.

PMID- 9011500
TI  - [Methods of production and perspectives for use of transgenic domestic animals].
AB  - The technique of microinjection is so far the only successful method of gene
      transfer in farm animals. Fertilized oocytes are collected from superovulated
      donors by flushing the oviducts and the exogenous gene construct is injected into
      the male pronucleus of zygotes before transfer into the oviducts or uteri of
      synchronized recipients. The resulting pups have to be tested for integration and
      expression of the foreign gene. Potential applications of gene transfer in farm
      animals are the improvement of growth parameters, the increase of disease
      resistance, the enhancement of reproduction rates, the increase of wool
      production of sheep, the alteration of metabolic pathways, the production of
      human hemoglobin in the blood of transgenic animals, the generation of transgenic
      animals as organ donors and the proteins in the milk of transgenic animals. Many
      studies showed, that farm animals are able to direct the expression of partially
      large amounts of foreign proteins for biomedical purposes into their milk.
      Therefore transgenic livestock could be an attractive alternative for
      conventional production methods.

PMID- 9011501
TI  - Protein neosynthesis by porcine oocytes matured in vivo and in vitro.
AB  - The protein pattern of individual porcine oocytes matured as intact cumulus
      oocyte complexes either in vivo or in vitro with or without FSH and LH for 43 h
      were investigated. The synthesis of a 53 kDa polypeptide ceased 21 h after hCG
      administration whereas a 44 kDa polypeptide were consistently absent in the
      protein patterns of nearly all of the in vivo maturing oocytes. Further on, a
      polypeptide with a relative molecular weight of 46000 persisted throughout
      maturation. A precipitous increase in the synthesis of two other proteins with
      relative molecular weights of 38000 and 28000, respectively, was observed at 9
      and 21 h after hCG injection. In in vitro matured oocytes with or without FSH and
      LH the synthesis of the 53 kDa band decreased after a culture period of 9h.
      Further on, the production of the 44 kDa polypeptide ceased only in oocytes
      incubated in FSH and LH supplemented media after 21 h of culture. On the other
      hand, the two proteins of Mr 38000 and 28000 appeared only in most of the protein
      profiles of oocytes cultured with FSH and LH for 43 h. The production of the 46
      kDa polypeptide during a 21 h culture period was significantly affected by the
      presence of additional granulosa cells in connection with the cumulus oocyte
      complex. Neither the appearance nor the disappearance of the 5 investigated bands
      was influenced by the presence or absence of the germinal vesicle after 21 h of
      culture. It is concluded that at least the addition of FSH and LH to the culture
      medium is necessary for cumulus oocytes complexes to synthesize a protein pattern
      closely corresponding to that produced by in vivo matured oocytes.

PMID- 9011502
TI  - [In vitro production of swine embryos].
AB  - In vitro production of transferable pig embryos is the key technology for an
      optimized utilization of high yielding farm animals, for the development of
      recent agricultural products and for the maintenance of genetic variability. Here
      we present research results of a recent larger study. Emphasis is on techniques
      to prepare sperm cells for IVF and to culture IVF-embryos in vitro up to
      blastocyst stages.

PMID- 9011503
TI  - [Preservation of genetic variation in domestic animals using biotechnical
      methods].
AB  - The conservation of endangered breeds as live animals is at present the main
      national strategy of the government and breeding organizations to maintain
      genetic diversity. Fourty-three breeds and some old strains of cattle, pig,
      sheep, goat and horses are currently involved. Cryopreservation and banks for
      sperm, embryos or DNA are another type of genetic material which could
      subsequently be used for breeding and production in agriculture. Present semen
      banks involve 9 endangered cattle breeds and also a small amount of deep-frozen
      sperm of some endangered sheep and horse breeds. Only 2 embryo banks are
      established in government projects for cattle breeds Murnau-Werdenfelser and the
      old type German black-white cattle.

PMID- 9011504
TI  - [Production of monozygotic multiple offspring in agricultural domestic animals].
AB  - The production of monozygotic twins/multiplets in livestock animal can be
      achieved either by microsurgical bisection of embryos at the morular- or
      blastocyst stage, isolation and proliferation of blastomeres from early cleavage
      stages or nuclear transfer. While the success rates of micro-surgical bisection
      are high in ruminants (pregnancy rates approximately 50%, twinning rates 20-40%)
      in polyovulatory species such as swine, the efficiency is low with an average of
      20% embryonic survival and 2% monozygotic twins that can positively identified
      via DNA-fingerprinting. Isolated blastomeres from multicellular embryos still
      possess great developmental capacity in vitro to progress to the blastocyst
      stage. However, their development in vivo is markedly reduced. This article
      summarizes the results obtained by the authors during several years of
      investigation. The results show for the first time that identical twins can be
      obtained in pigs which have been demonstrated to be a useful tool in biomedical
      research.

PMID- 9011505
TI  - [The yak--the Asiatic mountain cattle in science and practice].
AB  - A total of 15 million yak is indigenous to central Asia (China, Mongolia, Nepal,
      India and Bhutan) on an area of 220 m hectares. The animal is a six purpose
      cattle, including milk production, meat production, wool production, leather
      production, capacity for work as draught, riding and transport animals and energy
      production via dried manure. Moreover, anatomical and physiological peculiarities
      of this high mountain cattle are presented which can tolerate cold temperatures
      of -50 degrees C. Finally, chances and limitations of crossbreeding yaks and
      indigenous cattle are discussed.

PMID- 9011507
TI  - Transgenic animals in mutation research. Satellite conference to the 1996 meeting
      of the Environmental Mutagen Society. Sidney, British Columbia, Canada, March 20
      23, 1996.

PMID- 9011508
TI  - Biomaterials in a Simulated Oral Environment. Papers presented at the 1995 ADM
      Annual Meeting. La Jolla, CA, November 1995.

PMID- 9011506
TI  - [Physiological variables in calves and their significance for vitality and
      growth].
AB  - Calves from the dairy herd and from the mother cow herd and their dams were
      investigated just after parturition and the calves at the first two days of life
      and between fifteen and twenty days and than at ninety days of life as well using
      whole day heart rate and video recording, results of venous blood sample analysis
      and body growth and health criteria. The great variation of physiological
      variables in calves can partly be explained by maturity, degree of adaptation,
      gender, time of day and the birth course. Relationships between physiological
      variables and the adaptability, body growth performance and the degree of
      adaptation to specific rearing condition could be pointed out.

PMID- 9011509
TI  - Report of the 15th Artificial Insulin Delivery Systems Pancreas and Islet
      Transplantation (AIDSPIT) study group meeting.

PMID- 9011510
TI  - [Speech welcoming new academicians].

PMID- 9011511
TI  - [Speech on behalf of the new academicians].

PMID- 9011512
TI  - [Evaluation of topical calcipotriol in psoriasis].
AB  - Calcipotriol is an analogue of vitamin D3 with effect on epidermal
      keratinization, cellular division and modulation of immune response. An
      evaluation of its therapeutic effect when given in twenty-five psoriatic patient
      with less than 25% of their body surface affected was done. The medication was
      applied twice daily during six weeks on involved areas. The evolution was
      evaluated by the psoriatic area and severity index (PASI) analysis. The
      evaluation of initial and terminal PASI analysis revealed a decrease in the
      psoriatic activity that fluctuated from 25% to 100%, with a 61% average. A
      reactivation in the psoriatic lesion was noticed two weeks after the medication
      was halted; thereafter, the calcipotriol was restarted for an additional four
      weeks and a decrease in their PASI with a 74% average was achieved. There were no
      important side effects reported. Calcipotriol is effective in the treatment of
      psoriasis and it is an important addition to the therapeutic medications
      available to treat psoriasis. It is important to give the treatment for longer
      periods of time for evaluating the possibility to induce prolonged remissions.

PMID- 9011514
TI  - [New endometrial modulators in early pregnancy].
AB  - Cytokines synthesized by the uterus or placenta include those thought to be
      produced exclusively by, or though to act on, cells of the lymphohematopoietic
      system. Although many of these cytokines are protein mediators of the immune
      system effector phase, in the female reproductive tract their principal target
      cells and sites of synthesis are non-lymphohematopoietic cells. During pregnancy,
      uterine epithelial cells, decidual cells and trophoblast appear to be major
      sources of the classic lymphohematopoietic cytokines. This suggests two not
      necessarily exclusive alternatives: that these cells are extensions of, or are
      involved in, regulating the immune system, or that these factors regulate growth
      and differentiation of uterine and embryonic tissues. This paper analyzes the
      sites of synthesis, targets and possible functions of the cytokines during early
      pregnancy.

PMID- 9011515
TI  - [A centennial of two great discoveries in the history of medicine: hyperpiesis
      and the sphygmomanometer (1896-1996)].
AB  - This paper describes two outstanding contributions in the understanding and
      treatment of primary arterial hypertension and cardiovascular diseases. In 1896,
      Sir T. Clifford Allbutt reported a series of clinical cases associated with high
      intensity in the arterial pulse and no renal damage. He named this hyperpiesis to
      distinguish it from Bright's disease or chronic renal insufficiency. In the same
      year, Scipione Riva-Rocci invented the Sphygmomanometer which, in principle, is
      still used today. Also, this paper describes the research work which would lead
      to the development of the blood pressure measurement device. This development is
      as significant now as it was then.

PMID- 9011513
TI  - [Impact of new methodologies in the study of parasites].

PMID- 9011516
TI  - [The first medicine and surgery books published in the New World].

PMID- 9011518
TI  - [Advances in molecular genetics in the study of obesity].

PMID- 9011517
TI  - [Anatomic delineation by myelin].

PMID- 9011519
TI  - [The use of several drugs and their risks in pregnancy].

PMID- 9011520
TI  - [Epidemic of AIDS in Mexico. Global analysis 1981-1996].

PMID- 9011521
TI  - [Informed consent in health legislation of Mexico].
AB  - This paper deals with informed consent in Mexican Health Legislation in the
      context of a contract regulated by the Mexican Civil Code, in which a patient
      capable of making a thoughtful decision agrees to a specific plan of medical
      management and has received sufficient information, in a clear and explicit
      manner so that he/she can make a decision and in consequence agrees, or does not
      agree, to a course of action and to its consequences, under the Nuremberg Code.
      In Mexico, informed consent has recently been incorporated into health care
      legislation, and is basically oriented toward the field of medical research,
      while in other medical procedures, a legal authorization, and not an informed
      consent form is required, as with surgical procedures such as definitive
      fertility control (e.g. vasectomy or fallopian tube ligation). We emphasize the
      necessity of the adding of informed consent to Mexican health legislation in
      general, substituting it for other terms to legalize medical action, such as
      authorization, permission, dispositioned compliance, acceptance or approval-all
      of which have an essentially different and limited connotation, and are not
      Patient's Rights legal protector mechanisms, from our point of view.

PMID- 9011522
TI  - [Gastroesophageal reflux in an infant].

PMID- 9011523
TI  - Anaerobic degradation of halogenated benzoic acids coupled to denitrification
      observed in a variety of sediment and soil samples.
AB  - Denitrifying enrichment cultures utilizing monochlorinated benzoic acids as a
      carbon source were established using sediments and soils from a variety of
      sources as inocula. Enrichment cultures from most of the sites readily degraded 3
      and 4-chlorobenzoate within 2-4 weeks. Upon refeeding, 3- and 4-chlorobenzoate
      were rapidly depleted, and stable denitrifying cultures were obtained by repeated
      dilution and refeeding of the substrates. 2-Chlorobenzoate, however, was only
      slowly metabolized and this activity was only observed in a few sites.
      Denitrifying consortia were maintained on either 3- or 4-chlorobenzoate as the
      sole source of carbon and energy and chlorobenzoate utilization was dependent on
      denitrification. These cultures were also capable of utilizing the corresponding
      brominated and iodinated benzoic acids, but the activity was specific to the
      position of the halogen substituent. Removal of halogen was stoichiometric,
      indicating that dehalogenation occurred at some step in metabolism.

PMID- 9011524
TI  - Pressure sore in a patient who underwent repair of a retinal tear with gas
      injection.
AB  - PURPOSE: To demonstrate a pressure sore following strict head positioning in a
      patient who underwent encircling band, vitrectomy and gas injection. METHODS: A
      male patient was admitted to the hospital with a large posterior horseshoe tear
      in the inferior temporal retina with severe vitreous traction and retinal
      detachment. Encircling band, vitrectomy cryotherapy and gas injection was
      performed. After surgery the patient was instructed to sit in a face-down
      position. RESULTS: A pressure sore resulted from prolonged immobility of the
      right elbow due to face-down positioning following encircling band, vitrectomy
      and gas injection. CONCLUSION: A patient may rarely have compulsive personality
      traits that result in extreme compliance to the physician's recommendations;
      therefore, general instructions given for head positioning should include
      permission for a change in position when required, at least for brief periods of
      time.

PMID- 9011525
TI  - Infant rearing in captive Hapalemur griseus alaotrensis: singleton versus twins.

PMID- 9011526
TI  - [No medicine without scientific evidence of effectiveness. Doubts regarding
      alternative medicine].

PMID- 9011527
TI  - [HIV prevention after needlestick injury: preventive possibilities not proven,
      but likely. Official recommendations are still unavailable].

PMID- 9011528
TI  - [Bad experiences with ambulatory nursing service. Interview by Dr. rer. nat.
      Anita Schweiger].

PMID- 9011529
TI  - [Dementias--diagnosis, differential diagnosis and therapy].
AB  - The most common cause of primary (degenerative) dementia in old age is
      Alzheimer's disease, with vascular forms of dementia taking second place.
      Endocrinopathies, normal pressure hydrocephalus and space-occupying lesions are
      frequent causes of secondary dementia. A multitude of further, more rare clinical
      presentations results in a wide differential diagnostic spectrum necessitating a
      careful diagnostic work-up of the demential syndrome before considering
      treatment. This work-up must include clinical, laboratory and equipment-based
      investigations. The multimodal therapeutic approach to dementia covers not only
      the elimination of treatable underlying causal conditions and the medical
      treatment of cognitive symptoms and psychiatric accompanying symptoms, but also
      non-medicamentous aspects.

PMID- 9011531
TI  - [Vaccinations in childhood and adulthood. 5: Vaccinations and pregnancy-
      contraindications for vaccinations].

PMID- 9011530
TI  - [Can age-dependent cognitive functions be measured? P300 potentials--concept of
      brain aging--early diagnosis of dementia processes].
AB  - Event related P300 potentials as the electrophysiological substrate of cognitive
      functions, such as the stimulus processing time (P300 latencies) and visual
      attention capacity (P300 amplitudes) are suitable for the analysis of age-related
      changes in cognitive human brain functions. P300 investigations carried out in a
      total of 330 test subjects aged between 18 and 98 years, showed an overall slight
      prolongation of the P300 latencies by 10 ms for each decade, as well as a
      discrete reduction in the P300 amplitudes of 1 microV. To describe the
      relationship between the P300 parameters and chronological age, polynomial
      regression models are more suitable than linear functions. This means that in
      middle-age, P300 potentials change only slightly while, from about the age of 60
      upwards, a noticeable acceleration in the P300 changes takes place. An
      interesting observation was the fact that the acceleration in the P300 latency
      increase occurred some 10 years earlier in women than in men, beginning in the
      early postmenopausal period. The polynomial course of the regression function for
      the age-dependence of P300 potentials might reflect the positive influence of
      socio-cultural factors on the aging of cognitive functions. The true extent of
      the age-related changes in cognitive functions, however, can be determined only
      with the aid of intra-individual longitudinal studies. This is of considerable
      importance for the early diagnosis of both metabolic and primarily degenerative
      encephalopathies.

PMID- 9011532
TI  - [Chronic venous insufficiency--from pathophysiology to therapy. 2: Sclerotherapy
      of varicose veins].
AB  - For the elimination of chronic ambulatory venous hypertension, sclerotherapy and
      surgical measures are employed in addition to compression treatment. These
      various measures should always be used in combination with each other. In the
      present article, one of a series, indications, contraindications and the
      practicalities of sclerotherapy are discussed in detail.

PMID- 9011533
TI  - [Ischemic heart diseases and coronary vasospasm in Japanese population].

PMID- 9011534
TI  - [Quality assurance in cardiology: Germany].
AB  - Quality assurance is a touchy subject: difficult to implement, time-demanding and
      expensive. The goal of quality assurance is to assist both the patients and the
      physicians. In addition to legal requirements, quality assurance is necessary for
      medical as well as economical reasons. It makes sense that the license to
      practice medicine does not automatically entail the right to perform all medical
      procedures; the development of new methods and the insights won from important
      scientific studies necessitates constant training. Furthermore, the decreasing
      allocation of funds for medical care combined with increased demand effected by
      new treatment methods and longer life expectancy force the development of
      instruments for specific and reasonable budgeting of medical expenditures. The
      primary goal of quality management in respect to economical regards must be the
      avoidance of unnecessary hospital admissions. But the patient must retain the
      right to choose the physician he prefers. The organization of the supervising
      structures in Germany is inconsistent: in 1995, a new Zentralstelle der Deutschen
      Arzteschaft zur Qualitatssicherung in der Medizin (German Physicians Headquarters
      for Quality Assurance in Medicine) was founded; it is proportionally staffed by
      representatives of the Bundesarztekammer (BAK, Federal Board of Physicians) and
      the Kassenarztliche Bundesvereinigung (KBV, Federal Commission of Panel
      Physicians). Furthermore, there is the Arbeitsgemeinschaft zur Forderung der
      Qualitatssicherung in der Medizin (Working Group for the Advancement of Quality
      Assurance in Medicine), in which the Bundesministerium fur Gesundheit (Federal
      Ministry of Health) and the Kassenarztliche Vereinigung (KV, Public Health
      Insurance Providers) are represented. The KV is already seeing to it that
      stricter regulations govern physicians with private practice than those governing
      hospital physicians. There are three data banks existing on a voluntary basis for
      invasive diagnostic and therapy: a general, annual survey with baseline data from
      all German cardiac catheter laboratories; a data bank for storing records of
      PTCA's performed primarily in non-university-affiliated cardiac catheter labs
      (ALKK); and a data bank for recording diagnostic cardiac catheterization and
      PTCA's performed by physicians with private practice (BNK). In 1994, 15% of the
      diagnostic catheterizations and 16% of the coronary interventions were performed
      by physicians with private practice. Our survey shows that only 58% of German
      institutions record the data with a computer, 60% use their own developments;
      thus, the majority of groups in Germany are not linked to a central data bank.
      The least requirement for quality assurance should be the recording of major and
      minor complications as well as a comparison of one's own data with those of a
      central data bank.

PMID- 9011535
TI  - [Quality assurance in invasive cardiology: Switzerland].
AB  - In Switzerland, since 1985 mortality and morbidity data concerning either
      diagnostic and therapeutical coronary catheterization have been annually
      collected and analyzed. All interventional centres of the country (1994: 5
      universities, 9 private and 3 public non academic hospitals) delivered their
      respective data. While there was a marked increase in diagnostic catheterizations
      (1989: 11'197, 1994: 20'603) and PTCAs (1989: 1'976, 1994: 5'590), the incidence
      of procedure related myocardial infarctions, emergency coronary artery bypass
      graftings (CABG) and in-hospital deaths evolved as shown in table 1 (results
      separated for university and non-university centres). Procedure related
      myocardial infarction and emergency CABG rates in patients undergoing PTCA have
      dropped from 2.1% to 0.9% and 3.1% to 1%, respectively, within 5 years. In the
      same period of time, the incidence of myocardial infarction after PTCA slightly
      increased from 0.7% to 0.9%. The higher rates of infarction and death in
      university hospitals do not necessarily mean poor quality of treatment but may
      reflect a more complex patient population in these centres. Furthermore, as
      declaring complications tends to be influenced by the concern of a negative
      impact on referrals, our data probably underestimate the true complications
      rates. For future surveys we consider anonymous data presentation and per-sonal
      audits at the individual centres.

PMID- 9011536
TI  - Quality control for invasive cardiology: Holland.
AB  - Although no official registration of indications, treatments and results in
      patients with coronary heart disease has taken place in Holland, the following
      authorities and commissions have introduced guidelines for quality control: the
      Dutch government, the Dutch Society of Cardiology, the Working Group on
      Interventional Cardiology and the health insurers. Until 1991, the right to
      perform coronary interventions was tied to a license issued by the Ministry of
      Health. New recommendations were delineated 5 years ago: at least 500
      interventions must be annually performed by 5 interventional cardiologists, i.e.
      ca. 100 interventions annually per cardiologist. No interventional cardiology may
      be performed without an in-house cardiac surgery and vice versa. In a survey by
      the Dutch Society of Cardiology on the quality of the Dutch centers, PTCA
      mortality was ca. 0.3%, infarction rate was ca. 2%. An emergency bypass operation
      was necessary in 1.0 to 1.6% of the cases; the surgical team was on immediate
      alert for 11% of the patients. Selection of patients without risk was deemed
      impossible. Despite objections by some members the Dutch Society of Cardiology,
      it was recommended that cardiac surgery and interventions should not be
      separated. Data from health insurers showed no inappropriate indications for
      PTCA. The DUCAT-study, which used the RAND criteria, showed PTCA indications to
      be correct in more than 90% of the cases. The Dutch government wants to control
      the expansion of PTCA centers, so it is no wonder that waiting lists are becoming
      longer.

PMID- 9011537
TI  - [Quality assurance in invasive and interventional cardiology in Austria for the
      1995 calendar year].
AB  - A complete national database is the prerequisite for quality control, quality
      management and improvement. In Austria, we are reaching for this goal since more
      than 3 years. 23969 diagnostic coronary angiographies (CA) and 5898 PTCA were
      performed in all 25 adult-centers (out of which 18 perform PTCA) in Austria
      during the year 1995. This is an increase of 13.6% concerning CA and a 19.5%
      increase in PTCA compared to 1994. 50% of all PTCA were done during the
      diagnostic study (CA), direct PTCA for ongoing infarction in 2.8%. Concerning
      "new devices", 1572 stents (27% of the PTCA cases) were implanted in 1995.
      Hospital mortality after PTCA was 0.5% (unchanged to the years 1992 and 1993),
      emergency bypass surgery rate after PTCA was 0.8% (0.7% during the year 1993),
      and 1.3% of the patients suffered a myocardial infarction due to PTCA in the cath
      lab (1.4% during 1994). International comparison shows Austria under the top
      nations with 2996 CA and 737 PTCA per million inhabitants, corresponding to a
      ratio of 41% PTCA and CABG per 100 CA. Out of 18 centers with PTCA-activity
      ischemia was proven to be present before PTCA in 2729 patients within 11 centers,
      primary-success-rate was documented in 14 centers concerning 3703 patients and a
      controlling exercise stress test within 3 months after PTCA was reported by 8
      centers for 1555 patients. Local logbooks with continuous readings of
      complications, guidelines and monitor visits (audits) within all cath-labs in
      Austria turned out to be a better tool for quality control than computer
      databases. But additional electronic databases will be necessary in the future.
      Austria is the only nation worldwide to support a complete national database with
      controlled numbers and parameters since more than three years, including complete
      yearly monitor visits and feedback reports. We experienced no single negative
      reaction to our activities, but find them necessary for further quality
      management targets.

PMID- 9011538
TI  - [Quality management from the viewpoint of the Federal Public Health Ministry].
AB  - A recent analysis of quality assurance measures used by German health care
      providers, which was conducted by order of the German Federal Ministry of Health,
      documented a large heterogeneity of methods, a missing validation for most
      measures, and the lack of a unifying framework. The "Total Quality Management"
      strategy, which originally was developed for industrial purposes, may provide
      such a unifying framework if adapted to the health care setting. Therefore, the
      German Federal Ministry of Health encourages the introduction of the "Total
      Quality Management" philosophy into the German health care system and will
      support this process by providing educational material. Since in Germany economic
      factors have an increasing impact on health care providers, which absolutely is
      intended by the legislative power, the application of "Total Quality Management"
      strategies will not only become a major competitive factor for providers, but may
      also improve patient outcome and satisfaction and reduce resource consumption.

PMID- 9011539
TI  - [Development of standards for quality management in interventional cardiology].
AB  - Standardization is one of the fundamental methods for quality management.
      Standards describe first requirements for adequate delivery of diagnostic and
      therapeutic services (e.g. in the format of guidelines and protocols), second
      they define core data sets for documentation of real clinical outcome and of
      process and structure quality or third they define normal values (standards in
      the strict sense) or thresholds for critical parameters. This standardization is
      increasingly performed by the professional societies in international
      collaboration. We report on the parallel development of methodology. Presently
      standards for documentation and guidelines are being developed for the areas of
      cardiac interventional and surgical therapy. Three main methods are described.
      First, the common approach to guideline definition becomes more formalized as
      exemplified by the consensus approaches of the RAND group and of physicians in
      The Netherlands. Second, the definition of core data sets for quality assurance
      is increasingly based on the statistical evaluation of large interventional
      databases with the goal of developing predictive models of outcome. Since some of
      these methods are not yet fully reliable, it is still necessary to combine the
      results of predictive modelling with consensus on clinical practice. Figure 1
      describes one of these approaches to data standards definition. These methods are
      currently developed within the new Cardiovascular Data Standards Initiative of
      the American College of Cardiology (ACC) that is open for international
      collaboration. Figure 2 describes a parallel approach for standardization of
      digital image communication in angiocardiography. As shown in Figure 3, these
      data set standards and imaging standards will be applied not only in quality
      assurance, but also in shared care. Third, the PRESTIGE project of the European
      Commission is developing computerized tools that support terminology support,
      guideline authoring, guideline dissemination and protocol-directed care. We show
      that the elements described can be put to use within the unifying framework
      depicted in Figure 4. This guideline approach that is fully integrated into daily
      care delivery provides the physician with instant feedback from the guideline
      and, in addition, with periodic quality reports based on a comparison of the
      local clinical reality with the recommendations from the guideline. In our
      extended concept, these deviations are in addition symmetrically used to trigger,
      where necessary, the process of evaluation of the guideline. The often poor
      acceptance of guidelines should be improved both by integrating them into daily
      practice and by providing a feedback to the guideline authoring committee. We
      conclude that standardization activities are now entering into a new era due to
      increased involvement of physicians, international collaboration, integrated
      approaches to quality management, and improved computerized tools.

PMID- 9011540
TI  - Radiofrequency catheter ablation of a nodoventricular Mahaim tract.
AB  - We report the case of a patient with both a left bundle branch block-preexcited
      tachycardia using a Mahaim bundle and a tachycardia exhibiting a left bundle
      branch pattern without preexcited complexes related to an AV nodal reentrant
      tachycardia. Successful ablation of the nodoventricular tract was obtained in the
      posteroseptal location in the AV node region. The pattern of Wolff-Parkinson
      White (WPW) syndrome and both forms of tachycardia disappeared.

PMID- 9011541
TI  - [Intravascular sonographic findings after orthotopic heart transplantation:
      comparison with clinical factors].
AB  - 30 patients (mean age 51.4 +/- 11.6 years; female n = 6) were studied early after
      orthotopic heart transplantation (11.6 +/- 5.5 weeks). Twelve recipients had
      undergone specific treatment for biopsy proven rejection. Using a mechanical
      intravascular ultrasound device (3.5-F catheter), 153 coronary artery segments
      (16 left coronary main stem, 122 left anterior descending artery, 15 left
      circumflex artery) were studied. Intimal index and circumferential extension of a
      three-layer appearance of the vessel wall were assessed. In all segments,
      systolic-diastolic changes in area (delta A) with respect to vessel area and
      pressure (delta P) were used to study normalized compliance (normalized
      compliance = [delta A/A]/delta P [mm Hg-1 x 10(3)]). Intravascular ultrasound
      findings were correlated to perioperative ischemia time, LDL/HDL-ratio, Lp(a) and
      donor age. In a subgroup of 13 recipients, intravascular ultrasound investigation
      was repeated after an interval of 67.4 +/- 10.2 weeks. At first investigation,
      mean intimal index of all coronary segments was 0.07 +/- 0.10. Mean
      circumferential extension of a three-layer appearance of the vessel wall was 84
      +/- 112 degrees. Normalized compliance was 2.43 +/- 1.90 mm Hg-1 in the left main
      stem 2.45 +/- 1.47 mm Hg-1 within the left anterior descending artery, and 2.66
      +/- 1.72 mm Hg-1 within the circumflex artery (differences n.s.). No correlation
      was found between intimal index and normalized compliance (r = -0.322), nor
      between circumferential extension of intimal thickening and normalized compliance
      (r = -0.362). Furthermore, there was no correlation between normalized compliance
      and donor age. Normalized compliance was significantly lower in recipients with
      proven rejection than in those without (1.76 +/- 0.81 versus 2.95 +/- 1.22 mm Hg
      1, p = 0.005). Both, intimal index and circumferential extension of intimal
      thickening, were significantly higher in recipients following rejection periods
      (p < 0.05). The extent of coronary vessel wall alterations on ultrasound
      correlated to donor age but not to perioperative ischemia time, LDL/HDL-ratio and
      Lp(a). Re-investigation of a subgroup of 13 recipients 67.4 +/- 10.2 weeks after
      the first study showed an insignificant increase of the intimal index (from 0.03
      to 0.09) and of the circumferential extension of intimal thickening (from 40 to
      111 degrees). Normalized compliance changed from 2.53 +/- 1.48 to 2.87 +/- 1.33
      mm Hg-1 (differences n.s.). Early after orthotopic heart transplantation, a
      significant correlation between atherosclerotic coronary vessel wall alterations
      assessed by intravascular ultrasound and donor age can be confirmed. Heart
      recipients following rejection periods present with significantly more
      atherosclerotic vessel wall alterations and a severely reduced compliance of the
      coronary vessels.

PMID- 9011542
TI  - [Adults with congenital heart defects--clinical spectrum and surgical
      management].
AB  - Two hundred adults who underwent surgery for congenital heart disease at our
      institution within a four year period were the basis for this report. Clinical
      data was obtained, i.e. demographic details, past medical history, physical
      findings, EKGs, echocardiograms, catheterization and angiography material as well
      as the New York Heart Association (NYHA) class. Intraoperative findings,
      perioperative management, complications and morbidity and mortality were
      assessed. After discharge the patients were followed on an outpatient basis.
      Again the clinical findings, laboratory results and NYHA class were recorded. Age
      ranged from 16 to 75 years (mean = 38). There were 114 females and 86 males. 178
      patients had primary surgical correction, 18 were reoperated after prior
      correction and 4 underwent palliation. Eighty-three percent of the patients were
      symptomatic preoperatively. Seventeen percent were diagnosed per chance, for
      example by a preemployment physical examination, without a prior history of heart
      disease. The patients were grouped according to related diagnoses (Table 1).
      Among the 130 patients with left to right shunts, 112 had an atrial septal
      defect, 7 a ventricular septal defect, 5 a persistent ductus arteriosus, and 6
      partial anomalous pulmonary venous return. Atrial flutter or fibrillation
      occurred in approximately 10% of all patients with atrial septal defects. It was
      terminated either by rapid overdrive pacing or DC cardioversion. Postoperatively
      the patients with pulmonary hypertension were monitored invasively with arterial
      lines and thermodilution catheters. Therapy consisted of alkalization,
      hyperventilation and sedation. There was only one postoperative death in this
      patient group due to marked pulmonary hypertension (1/130 = 0.8%). Nineteen
      adults had obstruction to right or left ventricular outflow. Surgery included
      valvotomy, infundibulectomy and valve replacement by homograft or mechanical
      valve. One patient with multiple previous surgeries expired due to bleeding (3%).
      Thirteen patients had coarctation. All of them were hypertensive, some on
      medication. Surgery consisted of aortic patchplasty or interposition of a graft.
      There was no mortality. Perioperative antihypertensive therapy was necessary in
      most patients and consisted of nifedipin, nitroprussid or propanolol
      intravenously. Upon follow up 11 patients became normotensive, 8 of these without
      the need for medication. Fifteen cyanotic patients underwent 11 corrective and 4
      shunt procedures (3 with tricuspid atresia, 10 with Tetralogy of Fallot and 2
      with complex cyanotic heart disease. Three died due to low cardiac output or
      dysrhythmias (20%). The survivors improved their clinical status markedly. Seven
      adults with Ebstein's disease had valve reconstruction and/or ASD closure. Five
      had recurrent supraventricular tachycardia, 2 paradoxical emboli with
      neurological symptoms and 4 out of 7 had decreased exercise tolerance. One
      patient died postoperatively because of dysrhythmias (14%). Sixteen patients had
      a variety of defects, i.e. status post Rastelli operation and conduit
      obstruction, status post Tetralogy of Fallot with pulmonary valvar disease,
      corrected transposition with left AV valve insufficiency, congenital mitral valve
      disease and double aortic arch, no deaths. The overall operative mortality was
      6/200 = 3%. the late mortality was 4/200 = 2%. The morbidity included 7
      reoperations due to bleeding. Five patients needed short-term hemodialysis. One
      patient developed hemiplegia and two patients had permanent decrease of their
      left ventricular function. The mean length of follow up was 21 months. The
      clinical status improved from a NYHA class mean of 2.1 +/- 0.9 to 1.2 +/- 0.45 (p
      < 0.001). In Germany significant numbers of adults with operated and unoperated
      congenital heart disease do exist. Detection of these patients can be difficult
      due to inconspicuous murmurs or stable clinical status.

PMID- 9011543
TI  - [Diagnostic methods and standards in sleep medicine].

PMID- 9011544
TI  - [Differential diagnostic concepts in sleep medicine and their particular
      significance for the internist].

PMID- 9011545
TI  - [Effect of biological rhythm on sleep-wakefulness regulation].

PMID- 9011546
TI  - [Sleep--respiration--hemodynamics].

PMID- 9011547
TI  - [Sleep and depression].

PMID- 9011548
TI  - [Concepts in pharmacotherapy of insomnia].

PMID- 9011549
TI  - [Concepts of noninvasive ventilation].

PMID- 9011550
TI  - [A rare cause of adrenal cortex insufficiency].

PMID- 9011551
TI  - [46-year-old patient with recurrent hematemesis].

PMID- 9011552
TI  - [Can salivary gland swelling, edema and "direct" hyperbilirubinemia develop as
      sequelae of chronic administration of mianserin?].

PMID- 9011553
TI  - [How great is the value of oral hyposensitization in skin test assessed allergy
      in comparison with parenteral treatment?].

PMID- 9011554
TI  - [A 63-year-old otherwise healthy patient with bone metastatic prostate carcinoma
      of one year duration, with osteolytic metastasis to the left os pubis, os ischii
      and acetabulum].

PMID- 9011555
TI  - [Progress and continuing education in medicine. Practical medicine--what is new
      and important? 20th Interdisciplinary Forum of the Federal Physician Group,
      Cologne, January 1996].

PMID- 9011556
TI  - [Medical education. Educational reform--teaching must be in the classroom.
      Homburg/Saar International Symposium, 16-17 February 1996: Perspectives in
      Medical Education].

PMID- 9011557
TI  - [Angiotensin II receptor antagonists].

PMID- 9011558
TI  - [Bone metabolism and disorders].

PMID- 9011560
TI  - There ain't no justice.

PMID- 9011559
TI  - New antidepressant drug opens up important treatment and safety options.

PMID- 9011561
TI  - Number of ++submissions to the Journal of Biomechanics.

PMID- 9011562
TI  - Sleep apnea causes daytime hypertension.

PMID- 9011563
TI  - Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a
      canine model.
AB  - Several epidemiological studies have identified obstructive sleep apnea (OSA) as
      a risk factor for systemic hypertension, but a direct etiologic link between the
      two disorders has not been established definitively. Furthermore, the specific
      physiological mechanisms underlying the association between OSA and systemic
      hypertension have not been identified. The purpose of this study was to
      systematically examine the effects of OSA on daytime and nighttime blood pressure
      (BP). We induced OSA in four dogs by intermittent airway occlusion during
      nocturnal sleep. Daytime and nighttime BP were measured before, during, and after
      a 1-3-mo long period of OSA. OSA resulted in acute transient increases in
      nighttime BP to a maximum of 13.0+/-2.0 mmHg (mean+/-SEM), and eventually
      produced sustained daytime hypertension to a maximum of 15.7+/-4.3 mmHg. In a
      subsequent protocol, recurrent arousal from sleep without airway occlusion did
      not result in daytime hypertension. The demonstration that OSA can lead to the
      development of sustained hypertension has considerable importance, given the high
      prevalence of both disorders in the population.

PMID- 9011564
TI  - Bacterial infection induces nitric oxide synthase in human neutrophils.
AB  - The identification of human inflammatory cells that express inducible nitric
      oxide synthase and the clarification of the role of inducible nitric oxide
      synthase in human infectious or inflammatory processes have been elusive. In
      neutrophil-enriched fractions from urine, we demonstrate a 43-fold increase in
      nitric oxide synthase activity in patients with urinary tract infections compared
      with that in neutrophil-enriched fractions from noninfected controls. Partially
      purified inducible nitric oxide synthase is primarily membrane associated,
      calcium independent, and inhibited by arginine analogues with a rank order
      consistent with that of purified human inducible nitric oxide synthase.
      Molecular, biochemical, and immunocytochemical evidence unequivocally identifies
      inducible nitric oxide synthase as the major nitric oxide synthase isoform found
      in neutrophils isolated from urine during urinary tract infections. Elevated
      inducible nitric oxide synthase activity and elevated nitric oxide synthase
      protein measured in patients with urinary tract infections and treated with
      antibiotics does not decrease until 6-10 d of antibiotic treatment. The extended
      elevation of neutrophil inducible nitric oxide synthase during urinary tract
      infections may have both antimicrobial and proinflammatory functions.

PMID- 9011565
TI  - Autocrine role of interleukin 1beta in altered responsiveness of atopic asthmatic
      sensitized airway smooth muscle.
AB  - The role of IL-1beta in regulating altered airway responsiveness in the
      atopic/asthmatic sensitized state was examined in isolated rabbit tracheal smooth
      muscle (TSM) tissue and cultured cells passively sensitized with sera from atopic
      asthmatic patients or nonatopic/nonasthmatic (control) subjects. During half
      maximal isometric contraction of the tissues with acetylcholine, relative to
      control TSM, the atopic sensitized TSM exhibited significant attenuation of both
      their maximal relaxation (P < 0.001) and sensitivity (i.e., -log dose producing
      50% maximal relaxation) to isoproterenol and PGE2 (P < 0.05), whereas the
      relaxation responses to direct stimulation of adenylate cyclase with forskolin
      were similar in both tissue groups. The impaired relaxation responses to
      isoproterenol and PGE2 were ablated in sensitized TSM that were pretreated with
      either the IL-1 recombinant human receptor antagonist or an IL-1beta-neutralizing
      antibody. Moreover, extended studies demonstrated that, in contrast to their
      respective controls, both passively sensitized rabbit TSM tissue and cultured
      cells exhibited markedly induced expression of IL-1beta mRNA at 6 h after
      exposure to the sensitizing serum, a finding similar to that also obtained in
      passively sensitized human bronchial smooth muscle tissue. Finally, unlike their
      respective controls, passively sensitized TSM tissue and cultured cells also
      displayed progressively enhanced release of IL-1beta protein into the culture
      media for up to 24 h after exposure to atopic/asthmatic serum. Collectively,
      these observations provide new evidence demonstrating that the altered
      responsiveness of atopic/asthmatic sensitized airway smooth muscle is largely
      attributed to its autologously induced expression and autocrine action of IL
      1beta.

PMID- 9011566
TI  - Endothelin and angiotensin II stimulation of Na+-H+ exchange is impaired in
      cardiac hypertrophy.
AB  - We compared the effects of endothelin-1 (ET-1) on intracellular pH, intracellular
      [Ca2+]i, and cell contraction in hypertrophied adult ventricular myocytes from
      ascending aortic banded rats and age-matched controls. Intracellular pH (pH(i))
      was measured in individual myocytes with SNARF-1, and [Ca2+]i was measured with
      indo-1, simultaneous with cell motion. Experiments were performed at 36 degrees C
      in myocytes paced at 0.5 Hz in Hepes-buffered solution (pH(o) 7.40) containing
      1.2 mM CaCl2. At baseline, calibrated pH(i), diastolic and systolic [Ca2+]i
      values, and the amplitude of cell contraction were similar in hypertrophied and
      control myocytes. Exposure of the control myocytes to 10 nM ET-1 caused an
      increase in the amplitude of cell contraction to 163+/-22% of baseline (P <
      0.05), associated with intracellular alkalinization (pH(i) + 0.08+/-0.02 U, P <
      0.05) and a slight increase in peak systolic [Ca2+]i (104+/-11% of baseline, P <
      0.05). In contrast, in the hypertrophied myocytes, exposure to ET-1 did not
      increase the amplitude of cell contraction or cause intracellular alkalinization
      (-0.01+/-0.02 U, NS). Similar effects were observed in the hypertrophied and
      control myocytes in response to exposure to 10 nM angiotensin II. ET-1 also
      increased the rate of recovery from intracellular acidosis induced by the washout
      of NH4Cl in the control cells, but did not do so in the hypertrophied cells. In
      the presence of 10 microM 5-(N-ethyl-N-isopropyl)-amiloride, which inhibits Na+
      H+ exchange, ET-1 did not cause a positive inotropic effect or intracellular
      alkalinization in control cells. The activation of protein kinase C by exposure
      to phorbol ester caused intracellular alkalinization and it increased the rate of
      recovery from intracellular acidification induced by an NH4Cl pulse in control
      cells but not in hypertrophied cells. ET-1, as well as angiotensin II, and
      phorbol ester, fail to stimulate forward Na+-H+ exchange in adult hypertrophied
      myocytes. These data suggest a defect in the coupling of protein kinase C
      signaling with Na+-H+ exchange in adult hypertrophied myocytes.

PMID- 9011567
TI  - Heat shock factor-1 protein in heat shock factor-1 gene-transfected human
      epidermoid A431 cells requires phosphorylation before inducing heat shock protein
      70 production.
AB  - Heat shock factor-1 (HSF1) is a transcriptional factor that binds to heat shock
      elements located on the promoter region of heat shock protein genes. The purpose
      of this study was to further investigate the regulation of the expression of the
      heat shock protein-70 (HSP-70) gene. The HSF1 gene was inserted into pCDNA3
      plasmid and then transfected into human epidermoid A431 cells using the CaOP3
      method. Control cells were transfected with vector alone. Expression of HSP-70,
      HSF1, and HSF2 genes and protein were determined. We found a significant increase
      in the expression of the HSF1 gene, but not HSP-70 and HSF2 genes, in the HSF1
      gene-transfected cells. The amount of HSF1-heat shock element complex was
      significantly increased in both the nucleus and cytosol in HSF1 gene-transfected
      cells, indicating increased synthesis of HSF1. The amount of HSP-72 in these
      cells did not change. Therefore, overexpression of HSF1 protein failed to
      initiate transcription of the HSP-70 gene. Subsequently, we treated the cells
      with 1 microM PMA (a protein kinase C stimulator), and HSP-70 mRNA and protein
      were measured at 1 or 4 h of the treatment, respectively. The levels of both HSP
      70 mRNA and HSP-72 protein were significantly increased in nontransfected and
      transfected cells; the levels of HSP-72 in HSF1 gene-transfected cells were
      greater than that found in the vector-transfected cells. The PMA-induced increase
      in HSP-72 protein peaked 8 h after treatment with PMA and returned to baseline
      levels at 72 h. This increase was blocked by a PKC inhibitor, staurosporine.
      After treatment with PMA, HSF1 translocated quickly from cytosol to nucleus. The
      results suggest that phosphorylation of newly synthesized HSF1 and possibly of
      other factors are necessary for the induction of HSP-72. Activation of PKC can
      cause phosphorylation of HSF1, which leads to an enhanced but transient increase
      in HSP-70 production.

PMID- 9011569
TI  - Glycation-dependent, reactive oxygen species-mediated suppression of the insulin
      gene promoter activity in HIT cells.
AB  - Prolonged poor glycemic control in non-insulin-dependent diabetes mellitus
      patients often leads to a decline in insulin secretion from pancreatic beta
      cells, accompanied by a decrease in the insulin content of the cells. As a step
      toward elucidating the pathophysiological background of the so-called glucose
      toxicity to pancreatic beta cells, we induced glycation in HIT-T15 cells using a
      sugar with strong deoxidizing activity, D-ribose, and examined the effects on
      insulin gene transcription. The results of reporter gene analyses revealed that
      the insulin gene promoter is more sensitive to glycation than the control beta
      actin gene promoter; approximately 50 and 80% of the insulin gene promoter
      activity was lost when the cells were kept for 3 d in the presence of 40 and 60
      mM D-ribose, respectively. In agreement with this, decrease in the insulin mRNA
      and insulin content was observed in the glycation-induced cells. Also, gel
      mobility shift analyses using specific antiserum revealed decrease in the DNA
      binding activity of an insulin gene transcription factor, PDX-1/IPF1/STF-1. These
      effects of D-ribose seemed almost irreversible but could be prevented by addition
      of 1 mM aminoguanidine or 10 mM N-acetylcysteine, thus suggesting that glycation
      and reactive oxygen species, generated through the glycation reaction, serve as
      mediators of the phenomena. These observations suggest that protein glycation in
      pancreatic beta cells, which occurs in vivo under chronic hyperglycemia,
      suppresses insulin gene transcription and thus can explain part of the beta cell
      glucose toxicity.

PMID- 9011568
TI  - Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated
      human brain microvessels.
AB  - The peripheral production of leptin by adipose tissue and its putative effect as
      a signal of satiety in the central nervous system suggest that leptin gains
      access to the regions of the brain regulating energy balance by crossing the
      brain capillary endothelium, which constitutes the blood-brain barrier in vivo.
      The present experiments characterize the binding and internalization of mouse
      recombinant leptin in isolated human brain capillaries, an in vitro model of the
      human blood-brain barrier. Incubation of 125I-leptin with isolated human brain
      capillaries resulted in temperature-dependent binding: at 37 degrees C,
      approximately 65% of radiolabeled leptin was bound per milligram of capillary
      protein. Two-thirds of the bound radioactivity was resistant to removal by acid
      wash, demonstrating endocytosis of 125I-leptin into capillary cells. At 4 degrees
      C, binding to isolated capillaries was reduced to approximately 23%/mg of
      protein, the majority of which was acid wash resistant. Binding of 125I-leptin to
      brain capillary endothelial plasma membranes was saturable, described by a two
      site binding model with a high-affinity dissociation constant of 5.1+/-2.8 nM and
      maximal binding capacity of 0.34+/-0.16 pmol/mg of membrane protein. Addition of
      porcine insulin or insulin-like growth factor at a final concentration of 100 nM
      had a negligible effect on leptin binding. These results provide evidence for a
      leptin receptor that mediates saturable, specific, temperature-dependent binding
      and endocytosis of leptin at the human blood-brain barrier.

PMID- 9011570
TI  - Mutation of human keratin 18 in association with cryptogenic cirrhosis.
AB  - Mutations in 11 of the more than 20 keratin intermediate filaments cause several
      epidermal and oral associated diseases. No disease-associated mutations have been
      described in keratin 8 or 18 (K8/18) which are the major keratin pair in simple
      type epithelia, as found in the liver, pancreas, and intestine. However,
      transgenic mice that express mutant keratin 18 develop chronic hepatitis, and
      have an increased susceptibility to drug-induced hepatotoxicity. Also, ectopic
      expression of epidermal K14 in mouse liver results in chronic hepatitis, and
      disruption of mouse K8 leads to embryo lethality with extensive liver hemorrhage.
      We tested if patients with liver disease of unknown cause may harbor mutations in
      K18. We describe a his127-->leu (H127L) K18 mutation in a patient with
      cryptogenic cirrhosis that is germline transmitted. The K18 H127L isolated from
      the liver explant, or after expression in bacteria, showed an altered migration
      on two-dimensional gel analysis as compared with normal human liver or
      bacterially expressed K18. Electron microscopy of in vitro assembled K18 H127L
      and wild type K8 showed an assembly defect as compared with normal K8/18
      assembly. Our results suggest that mutations in K18 may be predispose to, or
      result in cryptogenic cirrhosis in humans.

PMID- 9011571
TI  - Chronic metabolic acidosis enhances NHE-3 protein abundance and transport
      activity in the rat thick ascending limb by increasing NHE-3 mRNA.
AB  - Chronic metabolic acidosis (CMA) is associated with an adaptive increase in the
      bicarbonate absorptive capacity of the rat medullary thick ascending limb (MTAL).
      To specify whether NHE-3, the apical MTAL Na/H exchanger, is involved in this
      adaptation, NHE-3 mRNA was quantified by a competitive RT-PCR using an internal
      standard which differed from the wild-type NHE-3 mRNA by an 80-bp deletion. CMA
      increased NHE-3 mRNA from 0.025+/-0.003 to 0.042+/-0.009 amol/ng total RNA (P <
      0.005). NHE-3 transport activity was measured as the initial proton flux rate
      calculated from the Na-dependent cell pH recovery of Na-depleted acidified MTAL
      cells in the presence of 50 microM HOE694 which specifically blocks NHE-1, the
      basolateral MTAL NHE isoform. CMA caused a 68% increase in NHE-3 transport
      activity (P < 0.001). In addition, CMA was associated with a 71% increase in NHE
      3 protein abundance (P < 0.05) as determined by Western blot analysis on MTAL
      membranes using a polyclonal antiserum directed against a cytoplasmic epitope of
      rat NHE-3. Thus, NHE-3 adapts to CMA in the rat MTAL via an increase in the mRNA
      transcript that enhances NHE-3 protein abundance and transport activity.

PMID- 9011572
TI  - The biology of PECAM-1.

PMID- 9011573
TI  - Development and characterization of desmoglein-3 specific T cells from patients
      with pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is a cutaneous autoimmune disease characterized by
      blister formation in the suprabasilar layers of skin and mucosae and anti
      desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratinocytes
      and circulating in the serum of patients. This disease can be reproduced in
      neonatal mice by passive transfer of patients' IgG, indicating that humoral
      immunity plays an important role in the pathogenesis of PV. Currently, the role
      of T lymphocytes in the development of PV is not clear. Here, we report that
      three immunoreactive segments of the ectodomain of Dsg3 specifically induced
      proliferation of T cells from PV patients. We found that T lymphocytes from 13
      out of 14 patients responded to at least one of three Dsg3 peptides. T cells from
      controls and other patient groups did not respond to these Dsg3 peptides. The
      major T cell population stimulated by these Dsg3 peptides was CD4 positive. Dsg3
      specific T cell lines and clones were developed and were shown to express a CD4
      positive memory T cell phenotype. Upon stimulation, these cell lines and clones
      secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were
      restricted to HLA-DR, and not -DQ and -DP, of the major histocompatibility
      complex. This information will help to elucidate the cellular immune
      abnormalities leading to production of pathogenic IgG autoantibodies in patients
      with PV.

PMID- 9011574
TI  - Tetrahydrobiopterin restores endothelial function in hypercholesterolemia.
AB  - In hypercholesterolemia, impaired nitric oxide activity has been associated with
      increased nitric oxide degradation by oxygen radicals. Deficiency of
      tetrahydrobiopterin, an essential cofactor of nitric oxide synthase, causes both
      impaired nitric oxide activity and increased oxygen radical formation. In this
      study we tested whether tetrahydrobiopterin deficiency contributes to the
      decreased nitric oxide activity observed in hypercholesterolemic patients.
      Therefore, L-mono-methyl-arginine to inhibit basal nitric oxide activity,
      serotonin to stimulate nitric oxide activity, and nitroprusside as endothelium
      independent vasodilator were infused in the brachial artery of 13 patients with
      familial hypercholesterolemia and 13 matched controls. The infusions were
      repeated during coinfusion of L-arginine (200 microg/kg/min), tetrahydrobiopterin
      (500 microg/min), or the combination of both compounds. Forearm vasomotion was
      assessed using forearm venous occlusion plethysmography and expressed as ratio of
      blood flow between measurement and control arm (M/C ratio). Tetrahydrobiopterin
      infusion alone did not alter M/C ratio. Both the attenuated L-mono-methyl
      arginine-induced vasoconstriction as well as the impaired serotonin-induced
      vasodilation were restored in patients during tetrahydrobiopterin infusion.
      Tetrahydrobiopterin had no effect in controls. In conclusion, this study
      demonstrates restoration of endothelial dysfunction by tetrahydrobiopterin
      suppletion in hypercholesterolemic patients.

PMID- 9011575
TI  - Polymerized hemoglobin restores cardiovascular and kidney function in endotoxin
      induced shock in the rat.
AB  - Sepsis and its complications, hypotension, shock, and multiorgan failure continue
      to represent a significant cause of mortality among hospitalized patients,
      affecting approximately 200,000 patients per year in the US and 100,000 in Europe
      (Dal Nogare, A.R. 1991. Am. J. Med. Sci. 302:50-65.). Incidence rates appear to
      be increasing, probably due to an increase in the population with risk factors
      such as diabetes or invasive procedures. Activation of cytokines by endotoxins
      and subsequent formation of nitric oxide is of central pathogeneic importance in
      sepsis. In this study we show that polymerized bovine hemoglobin (Biopure 2)
      restores both cardiovascular and renal functions in an endotoxin-induced shock
      model in rats. These effects are compared to those of the nitric oxide synthase
      inhibitor N(G)-nitro-L-arginine, and hydroxyethyl starch, the latter currently in
      clinical use for intravenous volume replacement. Our results clearly indicate
      that polymerized hemoglobin but not nitric oxide synthase inhibition or volume
      replacement normalize cardiovascular and kidney function in acute septic shock.
      This new therapeutic approach is readily applicable to controlled clinical trials
      because polymerized hemoglobin has been tested in humans and is therefore
      available for such studies.

PMID- 9011576
TI  - Hypoxia alters the subcellular distribution of protein kinase C isoforms in
      neonatal rat ventricular myocytes.
AB  - Cardiac myocytes coexpress multiple protein kinase C (PKC) isoforms which likely
      play distinct roles in signaling pathways leading to changes in contractility,
      hypertrophy, and ischemic preconditioning. Although PKC has been reported to be
      activated during myocardial ischemia, the effect of ischemia/hypoxia on
      individual PKC isoforms has not been determined. This study examines the effect
      of hypoxia on the subcellular distribution of individual PKC isoforms in cultured
      neonatal rat ventricular myocytes. Hypoxia induces the redistribution of PKC
      alpha and PKC epsilon from the soluble to the particulate compartment. This
      effect (which is presumed to represent activation of PKC alpha and PKC epsilon)
      is detectable by 1 h, sustained for up to 24 h, and reversible within 1 h of
      reoxygenation. Inhibition of phospholipase C with tricyclodecan-9-yl-xanthogenate
      (D609) prevents the hypoxia-induced redistribution of PKC alpha and PKC epsilon,
      whereas chelation of intracellular calcium with 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA) blocks the redistribution of PKC alpha, but
      not PKC epsilon; D609 and BAPTA do not influence the partitioning of PKC alpha
      and PKC epsilon in normoxic myocytes. Hypoxia, in contrast, decreases the
      membrane association of PKC delta via a mechanism that is distinct from the
      hypoxia-induced translocation/activation of PKC alpha/PKC epsilon, since the
      response is slower in onset, slowly reversible upon reoxygenation, and not
      blocked by D609 or BAPTA. The hypoxia-induced shift of PKC delta to the soluble
      compartment does not prevent subsequent 4-beta phorbol 12-myristate-13-acetate
      dependent translocation/activation of PKC delta. Hypoxia does not alter the
      abundance of any PKC isoform nor does it alter the subcellular distribution of
      PKC lambda. The selective hypoxia-induced activation of PKC isoforms through a
      pathway involving phospholipase C (PKC alpha/PKC epsilon) and intracellular
      calcium (PKC alpha) may critically influence cardiac myocyte contractility, gene
      expression, and/or tolerance to ischemia.

PMID- 9011577
TI  - Paraoxonase polymorphism Met-Leu54 is associated with modified serum
      concentrations of the enzyme. A possible link between the paraoxonase gene and
      increased risk of cardiovascular disease in diabetes.
AB  - Paraoxonase was identified as a genetic risk factor for cardiovascular disease
      (CVD) in recent studies focusing on a polymorphism affecting position 191. A
      second polymorphism of the paraoxonase gene affects position 54 and involves a
      methionine (M allele) to leucine (L allele) change. It was investigated in
      diabetic patients (n = 408) with and without vascular disease. There were highly
      significant differences in plasma concentrations and activities of paraoxonase
      between genotypes defined by the 54 polymorphism: MMAA, MLAA, LLAA; protein,
      65.3+/-18.0, 77.9+/-18.0, 93.5+/-26.0 microg/ml; P < 0.0001: activity
      (phenylacetate), 48.6+/-13.5, 64.1+/-14.5, 68.1+/-13.0 U/ml; P < 0.0001. The 191
      variant had little impact on paraoxonase concentrations. Homozygosity for the L
      allele was an independent risk factor for CVD (odds ratio 1.98 (1.07-3.83); P =
      0.031). A linkage disequilibrium (P < 0.0001) was apparent between the mutations
      giving rise to leucine and arginine at positions 54 and 191, respectively. The
      study underlines that susceptibility to CVD correlates with high activity
      paraoxonase alleles. The 54 polymorphism would appear to be of central importance
      to paraoxonase function by virtue of its association with modulated
      concentrations. The latter could explain the association between both the 54 and
      191 polymorphisms and CVD.

PMID- 9011578
TI  - Expression of the Gs protein alpha-subunit disrupts the normal program of
      differentiation in cultured murine myogenic cells.
AB  - The manner in which growth factors acting at the cell surface regulate activity
      of myogenic basic-helix-loop-helix proteins in the nucleus and thus control the
      fate of committed skeletal myoblasts remains poorly understood. In this study, we
      report that immunoreactive Gs protein alpha-subunits (Gs alpha) localize to
      nuclei of proliferating C2C12 myoblasts but not to nuclei of differentiated
      postmitotic C2C12 myotubes. To explore the biological significance of this
      observation, we placed a cDNA encoding Gs alpha in an expression vector under the
      control of a steroid-inducible promoter and isolated colonies of stably
      transfected C2C12 myoblasts. Dexamethasone-induced expression of activated Gs
      alpha markedly delayed differentiation in comparison with uninduced stably
      transfected cells, which differentiated normally in mitogen-depleted media.
      Northern blot analysis showed that impaired differentiation was associated with
      delayed up-regulation of MyoD and myogenin and delayed down-regulation of Id, a
      dominant negative inhibitor of differentiation. Similar impairment of
      differentiation could not be reproduced in wild-type C2C12 cells by increasing
      intracellular cAMP either with forskolin or treatment with a cell-permeable cAMP
      analog. However, treatment of myoblasts with cholera toxin markedly inhibited
      myogenic differentiation. Taken together, these findings suggest a novel role for
      Gs alpha in modulating myogenic differentiation.

PMID- 9011581
TI  - Sodium chloride increases the ciliary transportability of cystic fibrosis and
      bronchiectasis sputum on the mucus-depleted bovine trachea.
AB  - Mucus retention in the lungs is an important feature of several respiratory
      diseases (Regnis, J.A., M. Robinson, D.L. Bailey, P. Cook, P. Hooper, H.K. Chan,
      I. Gonda, G. Bautovich, and P.T.P. Bye. 1994. Am. J. Respir. Crit. Care Med.
      150:66-71 and Currie, D.C., D. Pavia, J.E. Agnew, M.T. Lopez-Vidriero, P.D.
      Diamond, P.J. Cole, and S.W. Clarke. 1987. Thorax. 42:126-130). On the mucus
      depleted bovine trachea, the ciliary transport rate of sputum from patients with
      cystic fibrosis and bronchiectasis of other causes was slow, but the rate was
      doubled by increasing the sodium chloride content by 90 mM. Increasing the sputum
      osmolality by inspissation or by the addition of nonelectrolytes had a similar
      effect. The viscoelasticity of sputum, but not the bovine ciliary beat frequency,
      was markedly saline dependent over the pathophysiological range. This suggests
      that low mucus salinity, not (as is generally assumed) its under-hydration,
      contributes to its retention in bronchiectasis due to cystic fibrosis and other
      causes, probably by affecting its rheology. It also indicates how the genetic
      defect in cystic fibrosis might lead to impaired mucus clearance. Therapies that
      increase the osmolality of lung mucus might benefit patients with mucus
      retention.

PMID- 9011580
TI  - In vivo and in vitro characterization of neonatal hyperparathyroidism resulting
      from a de novo, heterozygous mutation in the Ca2+-sensing receptor gene: normal
      maternal calcium homeostasis as a cause of secondary hyperparathyroidism in
      familial benign hypocalciuric hypercalcemia.
AB  - We characterized the in vivo, cellular and molecular pathophysiology of a case of
      neonatal hyperparathyroidism (NHPT) resulting from a de novo, heterozygous
      missense mutation in the gene for the extracellular Ca2+ (Ca2+(o))-sensing
      receptor (CaR). The female neonate presented with moderately severe
      hypercalcemia, markedly undermineralized bones, and multiple metaphyseal
      fractures. Subtotal parathyroidectomy was performed at 6 wk; hypercalcemia
      recurred rapidly but the bone disease improved gradually with reversion to an
      asymptomatic state resembling familial benign hypocalciuric hypercalcemia (FBHH).
      Dispersed parathyroid cells from the resected tissue showed a set-point (the
      level of Ca2+(o) half maximally inhibiting PTH secretion) substantially higher
      than for normal human parathyroid cells (approximately 1.8 vs. approximately 1.0
      mM, respectively); a similar increase in set-point was observed in vivo. The
      proband's CaR gene showed a missense mutation (R185Q) at codon 185, while her
      normocalcemic parents were homozygous for wild type (WT) CaR sequence. Transient
      expression of the mutant R185Q CaR in human embryonic kidney (HEK293) cells
      revealed a substantially attenuated Ca2+(o)-evoked accumulation of total inositol
      phosphates (IP), while cotransfection of normal and mutant receptors showed an
      EC50 (the level of Ca2+(o) eliciting a half-maximal increase in IPs) 37% higher
      than for WT CaR alone (6.3+/-0.4 vs. 4.6+/-0.3 mM Ca2+(o), respectively). Thus
      this de novo, heterozygous CaR mutation may exert a dominant negative action on
      the normal CaR, producing NHPT and more severe hypercalcemia than typically seen
      with FBHH. Moreover, normal maternal calcium homeostasis promoted additional
      secondary hyperparathyroidism in the fetus, contributing to the severity of the
      NHPT in this case with FBHH.

PMID- 9011579
TI  - Secretion of proinflammatory cytokines by epithelial cells in response to
      Chlamydia infection suggests a central role for epithelial cells in chlamydial
      pathogenesis.
AB  - Chlamydia species infect epithelial cells at mucosal surfaces, and are major
      causes of sexually transmitted diseases. Infection is characterized by
      inflammation which is exacerbated upon reinfection, ultimately leading to tissue
      damage and scarring. Although central for the development of disease
      manifestations, little is known about the mechanisms that initiate and sustain
      the inflammatory response to Chlamydia. Infection of cervical and colonic
      epithelial cells with Chlamydia trachomatis and Chlamydia psittaci is shown in
      the present studies to upregulate mRNA expression and secretion of the
      proinflammatory cytokines IL-8, GRO alpha, GM-CSF, and IL-6. In contrast to the
      rapid, but transient, cytokine induction following infection with other invasive
      bacteria, the epithelial cytokine response to Chlamydia was delayed until 20-24 h
      after infection, persisted throughout the chlamydial growth cycle (2-4 d), and
      required bacterial protein synthesis. Moreover, epithelial cell lines and primary
      endocervical epithelial cells released IL-1alpha after Chlamydia infection, and
      increased secretion of the proinflammatory cytokines could be inhibited by anti
      IL-1alpha. This suggests that IL-1alpha, released following lysis of infected
      epithelial cells, may amplify the inflammatory response by stimulating additional
      cytokine production by noninfected neighboring cells. These findings suggest a
      novel pathophysiologic concept wherein the acute host response to Chlamydia at
      mucosal surfaces is primarily initiated and sustained by epithelial cells, the
      first and major targets of chlamydial infection.

PMID- 9011583
TI  - Profiles in professionalism: 1996 ACD awardees. William John Gies Award.

PMID- 9011584
TI  - Distribution of nerve fibers in the standard incision for carpal tunnel
      decompression.
AB  - Twenty-two paired biopsy specimens of skin and subcutaneous tissue from the
      proximal and distal halves of the conventional curvilinear incision or carpal
      tunnel decompression were histologically examined. The specimens were
      immunohistochemically stained with S100 antibody to highlight the nerve fibers.
      The mean count of free nerve endings in the proximal biopsy site was 4.42/mm2
      (SD, 2.97; range, 1.23-12.27), compared to 4.2/mm2 (SD, 2.71; range, 1.01-10.50)
      in the distal biopsy specimens. This difference was not statistically significant
      (p = .20, Wilcoxon's signed ranks [matched pairs] test). The proximal incision
      site for carpal tunnel decompression did not appear to be more neuroreceptive
      than the distal incision site, providing no support for the implication of
      proximal incision sites in proximal scar tenderness.

PMID- 9011585
TI  - Macrophages, cytokines, and HIV.

PMID- 9011582
TI  - Effects of recombinant human growth hormone on muscle protein turnover in
      malnourished hemodialysis patients.
AB  - To assess the effect of recombinant human growth hormone (rhGH) on muscle protein
      metabolism in uremic patients with malnutrition, forearm [3H]phenylalanine
      kinetics were evaluated in six chronically wasted (body weight 79% of ideal
      weight) hemodialysis (HD) patients in a self-controlled, crossover study. Forearm
      protein dynamics were evaluated before, after a 6-wk course of rhGH (5 mg thrice
      weekly) and after a 6-wk washout period. After rhGH: (a) forearm phenylalanine
      net balance--the difference between phenylalanine incorporation into and
      phenylalanine release from muscle proteins--decreased by 46% (-8+/-2 vs. -15+/-2
      nmol/min x 100 ml at the baseline and -11+/-2 after washout, P < 0.02); (b)
      phenylalanine rate of disposal, an index of protein synthesis, increased by 25%
      (25+/-5 vs. 20+/-5 at the baseline and 20+/-4 after washout, P < 0.03); (c)
      phenylalanine rate of appearance, an index of protein degradation, was unchanged
      (33+/-5 vs. 35+/-5 at the baseline and 31+/-4 after washout); (d) forearm
      potassium release declined (0.24+/-0.13 vs. 0.60+/-0.15 microeq/min at the
      baseline, and 0.42+/-0.20 microeq/min after washout P < 0.03); (e) changes in the
      insulin-like growth factor binding protein (IGFBP)-1 levels and insulin-like
      growth factor-I (IGF-I)/IGFBP-3 ratios accounted for 15.1% and 47.1% of the
      percent variations in forearm net phenylalanine balance, respectively. Together,
      these two factors accounted for 62.2% of variations in forearm net phenylalanine
      balance during and after rhGH administration. These data indicate: (a) that rhGH
      administration in malnourished hemodialysis patients is followed by an increase
      in muscle protein synthesis and by a decrease in the negative muscle protein
      balance observed in the postabsorptive state; and (b) that the reduction in net
      protein catabolism obtained with rhGH can be accounted for by the associated
      changes in circulating free, but not total, IGF-I levels.

PMID- 9011586
TI  - Rapid lung cytokine accumulation and neutrophil recruitment after
      lipopolysaccharide inhalation by cigarette smokers and nonsmokers.
AB  - Inhalation of lipopolysaccharide (LPS) by humans rapidly recruits neutrophils to
      alveolar structures. Recruitment of neutrophils may be mediated in part by
      intrapulmonary release of cytokines such as tumor necrosis factor-alpha,
      interleukin (IL)-1beta, and IL-8, although the kinetics of cytokine accumulation
      and neutrophil recruitment to the lungs after LPS inhalation have not been
      determined. Release of some cytokines in response to LPS is reported to be
      decreased in smokers' alveolar macrophages compared with nonsmokers', suggesting
      responses to LPS may differ in smokers (S) and nonsmokers (NS). To assess the
      kinetics of early cytokine accumulation after LPS inhalation and to compare
      inflammation induced in LPS-exposed S and NS, we performed bronchoalveolar lavage
      (BAL) in 28 subjects (14 NS and 14 S) at 90 or 240 minutes after inhalation of
      aerosolized LPS (30 microg). BAL performed at 90 and 240 minutes after LPS
      inhalation recovered increased numbers of neutrophils and lymphocytes in both NS
      and S compared with an unexposed control group (10 NS, 10 S), with greater
      recovery of neutrophils in S than NS (p < 0.001). BAL fluid supernate
      concentrations of IL-8, IL-1beta, and tumor necrosis factor-alpha at 90 minutes
      were increased in S and NS compared with an unexposed control group. IL-8 and
      tumor necrosis factor-alpha concentrations were similar in S and NS; however, IL
      1beta concentrations were greater in S (p < 0.005). BAL fluid concentrations of
      IL-1beta and IL-8 at 90 minutes correlated with absolute neutrophil recovery in S
      and NS. These findings suggest that the rapid accumulation of cytokines,
      particularly IL-1beta and IL-8, contributes to lung neutrophil recruitment after
      LPS inhalation. In addition, parameters of pulmonary inflammation present in S
      after LPS inhalation are similar to or increased compared with those present in
      NS.

PMID- 9011587
TI  - Wegener's granulomatosis: a meta-analysis of 349 literary case reports.
AB  - We report the results of a meta-analysis of 349 patients with Wegener's
      granulomatosis (WG) that were described in the literature from 1979 onward. We
      describe the patients in terms of diagnosis (granulomas present or absent in
      biopsy samples from various organs, results of the anti-neutrophil cytoplasmic
      antibody [ANCA) test) and of the clinical impact of renal involvement.
      Furthermore, we report the incidence of histopathologic lesions that were found
      in 134 renal biopsy samples. Before and after the development of the ANCA test,
      the percentage of patients in whom WG was diagnosed with histologically proven
      granulomas is the same. However, after 1987 the diagnosis of the group without
      granulomas is frequently supported by a positive ANCA test result. For the entire
      group we found that patients without renal involvement (N = 82) were reported to
      have lower erythrocyte sedimentation rate (ESR), lower white blood cell count
      (WBC), less anemia, less hypertension, less occurrence of joint symptoms, and
      less multi-organ involvement than patients with renal involvement (N = 267). The
      most frequently reported lesion in the renal biopsy samples was extracapillary
      proliferation (70%), followed by fibrinoid necrosis of the glomerular tuft (54%).
      Renal granulomas were reported in only 7 biopsy samples.

PMID- 9011588
TI  - Staphylococcal exoproducts down-regulate cyclooxygenase 1 and 2 in peritoneal
      macrophages.
AB  - Peritoneal macrophages (PMOs) are important components of the host defense
      against microbial infection in patients undergoing continuous ambulatory
      peritoneal dialysis (CAPD). Incubation of human PMOs with cell-free supernatant
      (BFS), prepared from Staphylococcus aureus, inhibited prostaglandin E2 (PGE2) and
      thromboxane B2 (TXB2) production. Slot-blot analysis of cyclooxygenase-1 (Cox-1)
      and Cox-2 demonstrated a decrease in both Cox-1 (29%) and, to a greater extent,
      Cox-2 (65%) protein expression after BFS stimulation. When competitive polymerase
      chain reaction (PCR) was used, the peak levels of Cox-1 and Cox-2 messenger
      ribonucleic acid (mRNA) in unstimulated PMOs were 0.304+/-0.13 pmol/L and 9.61+/
      2.84 pmol/L (mean+/-SEM, n = 3), respectively. After exposure of samples to BFS
      for 30 minutes, the level of Cox-2 mRNA was reduced to 0.59+/-0.449 pmol/L (16
      fold reduction, p < 0.05), and the level of Cox-1 mRNA was reduced to 0.02+/
      0.002 pmol/L (15-fold reduction, p < 0.05). In contrast, these same PMOs showed
      an increased expression of IL-6 mRNA and increased secretion of IL-6 protein.
      These results indicate that prostaglandin production in PMOs is regulated by
      alterations in both immunoreactive Cox-1 and Cox-2. The down-regulation of Cox
      metabolism in these cells is primarily related to the delayed and depressed
      increase in the Cox-2 gene product.

PMID- 9011589
TI  - Adhesion and activation of platelets and polymorphonuclear granulocyte cells at
      TiO2 surfaces.
AB  - The initial reactions of two TiO2 surfaces with blood were investigated by short
      time exposure to capillary blood and analysis of surface-adsorbed plasma proteins
      and surface-adhering cells by using immunofluorescence techniques. Antibodies
      directed against platelet membrane antigen and P-selectin were used to visualize
      platelet adhesion and activation. Acridine orange and anti-CD11b were used to
      detect adhesion and activation of polymorphonuclear granulocytes (PMNs).
      Antibodies against thrombospondin were used as markers for platelet alpha
      granules. The fluorescence intensity was quantitated by computer-aided image
      analysis. Commercially pure, polished sheet titanium was oxidized in two
      different ways: (1) the natural oxide was dissolved with hydrofluoric acid and a
      new oxide layer was grown by oxidation in nitric acid, or (2) annealing was
      performed at 700 degrees C in air. Auger electron spectroscopy and x-ray
      photoelectron spectroscopy showed that both surfaces had similar composition
      consisting of TiO2 covered by a carbonaceous surface contamination layer. The
      thickness of the oxide layer was 4 nm on the acid-oxidized surface and 39 nm on
      the annealed surface. Optical profilometry and scanning electron microscopy
      showed that the acid-oxidized surface was rough and the annealed surface was
      smooth. The fibrinogen/prothrombin-thrombin ratio in the initial protein film
      differed between the surfaces. The number of adhering platelets was larger at the
      surface with a high surface concentration of adsorbed fibrinogen. Platelet
      activation (CD62) and priming of PMNs (CD 11b) were also significantly higher on
      the acid-oxidized surface. The results indicate that non-self recognition of
      biomaterials is an array of transient reactions comprising protein-material,
      protein-cell, and cell-cell interactions.

PMID- 9011590
TI  - Comparison of noninvasive methods for distinguishing steroid-sensitive nephrotic
      syndrome from focal glomerulosclerosis.
AB  - Although renal biopsy is the definitive investigation in kidney disorders and is
      particularly helpful in distinguishing steroid-responsive nephrotic syndrome
      (SRNS) from focal glomerulosclerosis (FGS), it is attended by a small risk to the
      patient. Accordingly, noninvasive tests have been used to predict the response to
      steroids and the underlying renal histologic diagnosis in nephrotic syndrome. The
      performance of these tests has, however, not been encouraging. We have therefore
      compared the reliability of the conventional selectivity index (SI) of serum and
      urinary transferrin and immunoglobulin G (IgG) against other tests of urinary
      proteins, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE),
      and isoelectric focusing (IEF). SI, SDS PAGE, and IEF were carried out in
      children with nephrotic syndrome within 2 months of clinical presentation. Thirty
      one children who had SRNS were compared with 26 who had biopsy-proved FGS and who
      were steroid resistant. SDS PAGE and IEF revealed excretion of albumin and
      transferrin only, with homogeneous anionic charge, respectively, in SRNS but
      unrestricted excretion of additional proteins IgG, beta2-microglobulin, and
      lysozyme with heterogeneity of electrical charge in FGS. With SDS PAGE and IEF we
      were able to predict all children who had SRNS and FGS; the SI test predicted all
      steroid-resistant patients with FGS but was able to predict only 41.7% of the
      patients with SRNS. Therefore the negative predictive value for steroid response
      was 58.8% by SI and 100% by SDS PAGE and IEF; the positive predictive value was
      100% by SI, SDS PAGE, and IEF. We illustrate the value of SDS PAGE in guiding
      management in a further seven children with FGS in whom there was either an
      initial discordance between renal biopsy results and steroid responsiveness or
      when biopsy was delayed. Accordingly, SDS PAGE and IEF of urinary proteins appear
      to be useful tests in the diagnosis and management of SRNS and FGS.

PMID- 9011591
TI  - Non-heme (Fe3+) in the lung increases with age in both humans and rats.
AB  - Increasing non-heme iron concentrations in host tissues are potentially
      significant, because they can be associated with an increased risk of injury
      including infections, fibrosis, and neoplasms. We tested the hypothesis that non
      heme (Fe3+) in the lung increases with age in both humans and rats. Human tissue
      was collected at autopsy before fixation occurred. The total number of specimens
      was 131 with 78 nonsmokers and 53 smokers. Tissue was hydrolyzed in 3 N
      hydrochloric acid and 10% trichloroacetic acid. Supernatant (Fe3+) was measured
      with a thiocyanate assay. Non-heme (Fe3+) increased with age in nonsmokers. The
      correlation coefficient between lung (Fe3+) and age in the nonsmokers was 0.58 (p
      < 0.0001). Iron stains were negative, whereas those for ferritin demonstrated
      increased uptake with aging. Smokers had significantly greater non-heme (Fe3+)
      relative to nonsmokers (101.1 and 46.0 micromol/L respectively; T = 11.44, p <
      0.0001). Lung non-heme (Fe3+) in smokers also increased with age (r = 0.75; p <
      0.0001). Iron stains demonstrated uptake in the proximity of retained pigmented
      material. Ferritin stains demonstrated intense uptake in both the macrophages and
      the airway and alveolar epithelium of smokers. An animal model was also analyzed
      for an effect of aging on lung non-heme (Fe3+). At specified times between 30 and
      186 days of age, rats (n = 48) were anesthetized and exsanguinated, and the lungs
      were excised. In rats, similar to humans, a positive correlation was seen between
      lung non-heme (Fe3+) and age (r = 0.73; p = 0.007). Stains for iron in rat lung
      were uniformly negative, whereas those for ferritin demonstrated increased uptake
      by airway and alveolar epithelium in older rats. We conclude that non-heme (Fe3+)
      in lung tissue increases with age in both humans and rats. Elevations in lung non
      heme (Fe3+) could contribute to an increased incidence of pneumonias, pulmonary
      fibrosis, and bronchogenic carcinoma observed among older individuals.

PMID- 9011592
TI  - Detection of renal allograft rejection by complement components C5A and TCC in
      plasma and urine.
AB  - Allograft rejection is associated with complement activation. Yet inconsistent
      results were obtained in evaluating plasma levels of complement factors or
      activation products as rejection markers. Therefore the human anaphylatoxin C5a
      and the soluble terminal complement complex (TCC) were measured by daily enzyme
      immunoassays on plasma (P) and urine (U) samples from 28 patients undergoing
      renal transplantation over a mean postoperative period of 25.8 days. The
      complement levels were evaluated longitudinally (cutoff of 100% increase on the
      previous day's level) during periods of rejection, stable graft function, acute
      tubular necrosis, and cytomegalovirus disease. Regarding the detection of 13
      acute rejection episodes, U-C5a showed a diagnostic accuracy of 81% (sensitivity
      of 85%, specificity of 77%), P-C5a one of 62%, and P-TCC one of only 30%. The U
      C5a increment (mean rise of 379%) preceded the clinical diagnosis of rejection by
      an average of 1.6 days. Cytomegalovirus diseases (n = 4) were associated with
      high P-C5a levels (mean increase of 251% by the time of the first detection of
      viral DNA). In contrast, resumption of kidney function after acute tubular
      necrosis (n = 10 periods) was heralded by marked peaks of U-C5a (x = 43.7
      microg/l). U-TCC was not detected in any clinical setting. In conclusion, as
      opposed to P-TCC, U-TCC, and P-C5a, the anaphylatoxin C5a, measured daily in
      urine, might have potential as an early and reliable marker for acute renal
      allograft rejection.

PMID- 9011593
TI  - Arterial ketone body ratio as a prognostic indicator in acute heart failure.
AB  - The arterial ketone body ratio (AKBR), an established clinical tool that reflects
      hepatic mitochondrial oxidation-reduction potential, predicts the outcome of
      patients with shock and multiple organ failure and the postoperative outcome in
      patients who have undergone major liver or heart surgery. The purpose of this
      study was to determine the prognostic significance of AKBR in patients with acute
      heart failure. The subjects of this study were 52 patients with acute heart
      failure. The following parameters were analyzed after Cox univariate hazard
      analysis was performed: AKBR, plasma norepinephrine, left ventricular ejection
      fraction, cardiac index, pulmonary arterial wedge pressure, sex, age, human
      atrial natriuretic peptide, endothelin-1, and cholesterol. The follow-up period
      was 30 weeks with cardiac death as the end point. Stepwise multivariate
      proportional hazard analysis revealed that AKBR was the most significant
      predictor of death, followed by norepinephrine and human atrial natriuretic
      peptide. Curve-fitting analysis revealed that the relationship between log
      (norepinephrine) and AKBR could best be described by two distinct lines, with
      their intersection at AKBR = 0.7 and norepinephrine = 418. With these results we
      conducted Kaplan-Meier analysis for AKBR > or = 0.7 and AKBR <0.7. The survival
      rate in patients with AKBR > or = 0.7 was 100%, whereas that in patients with
      AKBR <0.7 was 15% (p < 0.0001, log-rank analysis). These results indicate that
      AKBR is a novel independent predictor of death in heart failure.

PMID- 9011594
TI  - Roles of reactive oxygen species and antioxidant enzymes in murine daunomycin
      induced nephropathy.
AB  - We evaluated the roles of reactive oxygen species and intrinsic antioxidant
      enzymes in the development of daunomycin (DM)-induced nephropathy in mice. A
      single dose of DM (20 mg/kg intravenously) induced proteinuria by day 7 and the
      nephrotic syndrome by day 14 in DM-sensitive strain (A/J) but not in DM-resistant
      strain (C57BL/6J) (B6). Renal cortical lipid peroxide levels in the A/J mice
      significantly increased at days 2, 4, and 7 after DM injection, whereas no
      increase was observed in the B6 mice. The resistance to DM in B6 mice was
      associated with higher activities in renal cortical superoxide dismutase and
      glutathione peroxidase. The administration of superoxide dismutase or of
      dimethylthiourea significantly suppressed the DM-induced proteinuria in the A/J
      mice. Four days of superoxide dismutase or dimethylthiourea administration
      suppressed the proteinuria. These findings suggested that murine DM-nephropathy
      appeared to be mediated by reactive oxygen species and that intrinsic antioxidant
      enzyme activities may play an important role in the susceptibility to DM-induced
      nephropathy in mice.

PMID- 9011595
TI  - Gender-specific correlation of platelet ionized magnesium and serum low-density
      lipoprotein cholesterol concentrations in apparently healthy subjects.
AB  - We previously found an inverse correlation between platelet ionized magnesium
      concentration ((Mg2+)i) and serum total cholesterol concentration in normal male
      but not female subjects. In the present study, we determined the platelet (Mg2+)i
      by using a fluorescent ionized magnesium (Mg2+) indicator, FURAPTRA, and measured
      the serum concentrations of the following: total cholesterol; very-low-density
      lipoprotein cholesterol (VLDL-C); low-density lipoprotein cholesterol (LDL-C);
      high-density lipoprotein cholesterol (HDL-C); antioxidized low-density
      lipoprotein (LDL) autoantibodies; lipoprotein(a); apolipoproteins A-I (apo A-I)
      and B (apo B); triglycerides; estradiol-17 (E2); ceruloplasmin (Cp); and selected
      electrolytes, including total and ionized magnesium and calcium and total protein
      and albumin. In men, but not in women, platelet (Mg2+)i significantly inversely
      correlated with serum total cholesterol (r = -0.52, p < 0.02), LDL-C (r = -0.54,
      p < 0.009 by a "direct" method; r = -0.40, p < 0.05 by an electrophoretic
      method), and apo B (r = -0.42, p < 0.04). We found no significant correlations
      between platelet (Mg2+)i and any other variables, including serum total and
      ionized magnesium, antioxidized LDL autoantibodies, Cp, and E2. We speculate that
      decreased platelet (Mg2+)i is a possible marker for platelet membrane alterations
      that may affect platelet involvement in thrombosis and atherogenesis.

PMID- 9011596
TI  - Evaluation of oxygen availability with oxygen status algorithm in patients
      undergoing open heart surgery treated with epoetin beta.
AB  - We evaluated in a double-blind randomized study the effect of epoetin beta
      (recombinant human erythropoietin) therapy on oxygen status in patients
      undergoing cardiac surgery who were contraindicated for autologous blood
      donation. All 76 patients enrolled in this study were randomized to the two
      treatment groups (5 x 500 U epoetin beta or placebo/kg body weight intravenously
      over a 14-day period before surgery) and received 300 mg Fe2+ per day orally
      before surgery. Before and after surgery the lactate level and the following
      parameters according to the oxygen status algorithm by Siggaard-Andersen were
      evaluated: arterial oxygen tension (PaO2), effective hemoglobin concentration
      (ceHb), arterial oxygen saturation (SaO2), oxygen half saturation tension (p50),
      red cell 2.3 diphosphoglycerate (2.3 DPG), arterial total oxygen concentration
      (ctO2), concentration of extractable oxygen (cx), and oxygen compensation factor
      (Qx). Therapy with epoetin beta led to increases in ceHb, PaO2, ctO2, and cx and
      to a decrease in Qx before surgery (p < 0.05 for PaO2, p < 0.0001 for the other
      parameters vs placebo). The cx in patients who received epoetin beta rose by
      approximately 20%, thus indicating a considerable improvement in O2 delivery. In
      patients receiving placebo the hemoximetric parameters remained outside the
      normal limits at all times after surgery, but in the epoetin beta group PaO2,
      ctO2, cx, and Qx returned almost to their baseline values by the second or fifth
      postoperative day, even though the frequency of transfusions was significantly
      higher in the placebo group. Whereas p50 and 2.3 DPG fell in the placebo group
      after surgery, these two parameters were significantly higher in the epoetin beta
      group and led to a further increase in cx (from 24% to 38%) versus the placebo
      group as a result of the right shift in the hemoglobin O2-binding curve. The
      postoperative incidence and severity of lactic acidosis were higher in the
      placebo group. Preoperative epoetin beta therapy is a safe way of providing
      increased extractable O2 (by 24% to 38%) and decreasing the risk of lactic
      acidosis after surgery. This therapy has a more favorable effect on the O2
      binding curve than the transfusion of erythrocyte concentrate and enhances the
      effect of epoetin beta therapy on the postoperative oxygen status.

PMID- 9011598
TI  - Physician moaning syndrome.

PMID- 9011597
TI  - Doctor, are your patients starving?

PMID- 9011599
TI  - Breast cancer awareness.

PMID- 9011600
TI  - Advances in antimicrobial chemotherapy. A selection of papers from the 9th
      Mediterranean Congress of Chemotherapy. Milan, Italy, June 1994.

PMID- 9011601
TI  - [Dossier of prescription preparations].

PMID- 9011602
TI  - Oxidant stress activates a non-selective cation channel responsible for membrane
      depolarization in calf vascular endothelial cells.
AB  - 1. In vascular endothelial cells, oxidant stress increases cell Na+ content and
      inhibits the agonist-stimulated influx of external Ca2+. Further, oxidant stress
      increases uptake of Ca2+ into otherwise quiescent endothelial cells. To determine
      the mechanism responsible for altered Na+ and Ca2+ homeostasis, the present study
      examined the effect of oxidant stress on ionic current and channel activity in
      calf pulmonary artery endothelial cells. 2. Voltage-clamped control cells had a
      zero-current potential of -60 mV. Incubation of cells with the oxidant tert
      butylhydroperoxide (tBuOOH; 0.4 mM, 1 h) caused depolarization to -4 mV and
      activation of ionic current equally selective for Na+ and K+. 3. Cell-attached
      membrane patches made on tBuOOH-treated cells contained ion channels that had a
      bidirectional conductance of 30 pS and that were not present in patches from
      control cells. Inside-out patches excised from oxidant-treated cells showed the
      channel to be equally selective for Na+ and K+ and to allow inward Ca2+ current.
      4. Oxidant-activated channels were observed to display two gating modalities that
      were further evident during analysis of single-channel open probability. Neither
      modality was significantly affected by altering internal [Ca2+] (1 microM-10 nM).
      5. Activation of non-selective channels provides a possible mechanism by which
      oxidants may increase endothelial cell Na+ content. Channel permeability to Ca2+
      may account in part for the elevation of cytosolic free [Ca2+] that occurs in
      oxidant-treated cells. 6. Channel activation is associated with membrane
      depolarization, a mechanism that may contribute to oxidant inhibition of the
      agonist-stimulated Ca2+ influx pathway.

PMID- 9011603
TI  - Rapid activation of KATP channels by aldosterone in principal cells of frog skin.
AB  - 1. In epithelial cells of frog skin, potassium ions are recycled across the
      basolateral membrane via an inward-rectifier, ATP-sensitive K+ channel (KATP
      channel). In this study, we show that aldosterone has a stimulatory effect on
      KATP channel activity and we have investigated the involvement of Na+-H+ exchange
      and intracellular pH (pHi) in this phenomenon. 2. Aldosterone (10 nM) produced an
      increase in the open probability of the KATP channel within 15 min from 0.21 +/-
      0.05 to 0.93 +/- 0.10 (n = 8), measured in cell-attached patches. Aldosterone
      also increased the tolbutamide-sensitive K+ current across the basolateral
      membrane within 30 min from 17.2 +/- 1.9 to 30.3 +/- 1.6 microA cm-2 (n = 8) in
      nystatin-permeabilized whole skins. 3. The KATP channel is very sensitive to
      variations in cytosolic pH within the physiological range 7.0-7.4. 4. The
      intracellular pH of principal cells is regulated by Na+-H+ exchange, and the
      stimulatory effect of aldosterone on KATP channel activity was abolished by
      amiloride (100 microM) added on the basolateral side of the epithelium either
      before or after aldosterone treatment. 5. We propose that aldosterone activates
      the KATP channels via stimulation of Na+-H+ exchange. The rapidity of aldosterone
      activation of KATP channels is presented as evidence for a novel non-genomic
      steroid hormone effect on epithelial ion transport.

PMID- 9011604
TI  - Kinetics of the block by intracellular Mg2+ of the NMDA-activated channel in
      cultured rat neurons.
AB  - 1. Single-channel currents activated by the glutamate agonist N-methyl-D
      aspartate (NMDA) were recorded from outside-out patches of cultured rat cortical
      neurons in the presence of intracellular Mg2+ (Mgi2+). The rate constants of the
      block by Mgi2+ were measured using amplitude distribution analysis. 2. At a
      membrane potential of 0 mV, the blocking rate constant (k+) of Mgi2+ was
      estimated to be 2.1 x 10(7) M-1 S-1 and the unblocking rate constant (k-) 1.7 x
      15(5)s-1. The very fast rate constants of the block by Mgi2+ explain why channel
      flicker was not fully resolvable during block of the NMDA-activated single
      channel current by Mgi2+. 3. The blocking rate constant of Mgi2+ increased with
      increasing concentrations of Mgi2+. The unblocking rate constant was Mgi2+
      concentration independent. 4. The blocking rate constant increased e-fold per 64
      mV depolarization, whereas the unblocking rate constant decreased e-fold per 133
      mV depolarization. The dissociation constant (KD) calculated from the blocking
      rates (k-/k+) decreased e-fold per 43 mV depolarization, and had a value at 0 mV
      of 7.8 mM. These values are consistent with previous estimates obtained from the
      voltage-dependent inhibition of the single-channel current amplitude. Both
      results predict, based on the Woodhull model, that Mgi2+ traverses about one
      third of the membrane field to reach its blocking site. 5. The unblocking rate
      constant of Mgi2+ is one to two orders of magnitude faster than the previously
      reported unblocking rate constant of extracellular Mg2+ (Mgo2+) in the
      physiological voltage range, and their voltage dependencies are of opposite
      signs. These findings are consistent with the hypothesis that there are separate
      binding sites in the channel for Mgi2+ and Mgo2+. 6. Based on the blocking
      kinetics of Mgi2+ and Mgo2+, an energy profile of three barriers and two binding
      sites for Mg2+ is proposed.

PMID- 9011605
TI  - Effect of pentachlorophenol on calcium accumulation in barnacle muscle cells.
AB  - 1. The effect of extracellularly applied pentachlorophenol (PCP) was studied on
      the membrane potential (Vm) and Ca2+ uptake in isolated single skeletal muscle
      cells of Balanus nubilus. 2. When compared with the controls, 0.1 mM PCP induced
      a significant (P < 0.05) increase in Ca2+ uptake accompanied by membrane
      depolarization (9 mV at 45 min incubation). This depolarization was reduced by
      11% of extracellular Ca2+ (Cao2+) was replaced by Tris+ and by 50% if
      extracellular Na+ was also replaced by Tris+. 3. The Ca2+ channel blocker,
      verapamil (0.1 mM), completely inhibited the PCP-induced Ca2+ uptake as well as
      the membrane depolarization either in the absence or presence of Cao2+.
      Experiments on voltage-clamped cells show that the PCP-induced Ca2+ uptake was
      independent of the PCP-induced depolarization. 4. The results indicate that PCP
      induces activation of a verapamil-sensitive Ca2+ influx pathway (presumably L
      type Ca2+ channels) independent of Vm. The permeation of Ca2+, Na+ and Tris+
      through this pathway produces membrane depolarization in the following order of
      effectiveness: Ca2+ > Na+ > Tris+.

PMID- 9011606
TI  - Effects of intracellular Mg2+ on channel gating and steady-state responses of the
      NMDA receptor in cultured rat neurons.
AB  - 1. The effects of intracellular Mg2+ (Mgi2+) on the single N-methyl-D-aspartate
      (NMDA)-activated channel burst duration and frequency and on the mean NMDA
      activated patch current were studied in outside-out patches from cultured rat
      cortical neurons. The inhibition by Mgi2+ of mean patch and whole-cell currents
      were compared, and some possible explanations for the observed differences were
      investigated. 2. The burst duration at +60 mV did not depend on Mgi2+
      concentration, suggesting that the channel can close when blocked by Mgi2+. The
      number of bursts per second increased significantly in the presence of Mgi2+,
      suggesting that the rate of channel opening is higher when Mg2+ from the
      intracellular solution occupies its binding site. 3. Mgi2+ caused a voltage- and
      concentration-dependent inhibition of mean patch current. The inhibition is in
      quantitative agreement with the effects of Mgi2+ on the single-channel current
      and on burst parameters. 4. Based on the effects of Mgi2+ on burst parameters and
      on single-channel current, a four-state model in which the NMDA-activated channel
      can close while blocked by Mgi2+ is proposed. By fitting the model to the mean
      patch current data, we estimate that the rate of channel opening is increased by
      a factor of 1.4 when Mgi2+ occupies the channel. This estimation provides
      evidence that occupancy of the NMDA-activated channel by Mgi2+ destabilizes the
      closed state. 5. Mgi2+ reduced NMDA-activated whole-cell currents in a voltage-
      and concentration-dependent manner. However, normalized whole-cell and mean patch
      currents at positive voltages differed in two significant respects. First, when
      currents were recorded in a 0 Mg2+ pipette solution, whole-cell currents at
      positive voltages were smaller. Second, Mgi2+ appeared to inhibit whole-cell
      current less effectively than it inhibited mean patch current. 6. Inclusion of
      the Mg2+ chelators EDTA and ATP in 0 Mg2+ pipette solutions did not increase the
      whole-cell current measured at +60 mV. This observation suggests that the
      difference between normalized whole-cell and mean patch currents with 0 Mg2+
      pipette solution was not due to block of whole-cell currents by residual Mgi2+.
      7. When a pipette solution containing EGTA and Mg2+ was used to buffer Mgi2+,
      inhibition by Mgi2+ of the whole-cell current was enhanced, suggesting that the
      free Mg2+ concentration inside a neuron can remain below the pipette Mg2+
      concentration. However, we cannot exclude other explanations for the differences
      between the inhibition by Mg2+ of mean patch and whole-cell currents.

PMID- 9011607
TI  - Neuronal nicotinic alpha 7 receptor expressed in Xenopus oocytes presents five
      putative binding sites for methyllycaconitine.
AB  - 1. The recently isolated compound methyllycaconitine (MLA) is a plant toxin which
      is a competitive inhibitor of nicotinic acetylcholine receptors (nAChRs). We
      found that homomeric alpha 7 receptors display a very high sensitivity to MLA
      with an IC50 in the picomolar range. 2. The competitive nature of the alpha 7 MLA
      blockade was reinforced by the observation that this compound has no action on
      wild-type serotoninergic receptors (5-HT3), whereas it is a powerful antagonist
      of chimaeric receptors alpha 7-5-HT3. 3. The time course of MLA inhibition of the
      wild-type (WT) alpha 7 follows a monotonic exponential decay whose time constant
      is proportional to the MLA concentration and could be described by a bimolecular
      mechanism with a forward rate constant (k+) of 2.7 x 10(7) S-1 M-1. In contrast,
      recovery from MLA inhibition displays an S-shaped time course that is
      incompatible with a simple bimolecular reaction. 4. Given the pentameric nature
      of the neuronal nicotinic receptors, a linear chain model, including five
      putative MLA binding sites corresponding to the homomeric nature of alpha 7, is
      proposed. 5. Both onset and recovery data obtained on the alpha 7 wild-type
      receptor are adequately described by this model assuming that a single MLA
      molecule is sufficient to block receptor function. 6. Analysis of MLA blockade
      and recovery of reconstituted heteromeric alpha 4 beta 2 receptors reveals, as
      expected, a time course compatible with only two binding sites for the toxin and,
      thus, further supports the validity of our model.

PMID- 9011608
TI  - Paired-pulse facilitation and depression at unitary synapses in rat hippocampus:
      quantal fluctuation affects subsequent release.
AB  - 1. Excitatory synaptic transmission between pairs of monosynaptically coupled
      pyramidal cells was examined in rat hippocampal slice cultures. Action potentials
      were elicited in single CA3 pyramidal cells impaled with microelectrodes and
      unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell
      voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in
      response to single action potentials varied. The amplitude of EPSCs was altered
      by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single
      action potentials triggered the release of multiple quanta of glutamate. 3. When
      two action potentials were elicited in the presynaptic cell, the amplitude of the
      second EPSC was inversely related to the amplitude of the first. Paired-pulse
      facilitation (PPF) was observed when the first EPSC was small, i.e. the second
      EPSC was larger than the first, whereas paired-pulse depression (PPD) was
      observed when the first EPSC was large. 4. The number of trials displaying PPD
      was greater when release probability was increased, and smaller when release
      probability was decreased. 5. PPD was not postsynaptically mediated because it
      was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an
      interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD
      occurred within 5 s. 7. We propose that multiple release sites are formed by the
      axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is
      observed if the first action potential fails to release transmitter at most
      release sites. PPD is observed if the first action potential successfully
      triggers release at most release sites. 8. Our observations of PPF are consistent
      with the residual calcium hypothesis. We conclude that PPD results from a
      decrease in quantal content, perhaps due to short-term depletion of readily
      releasable vesicles.

PMID- 9011609
TI  - Endogenous monoamines inhibit glutamate transmission in the spinal trigeminal
      nucleus of the guinea-pig.
AB  - 1. With the use of whole-cell patch clamp recordings in slices of guinea-pig
      substantia gelatinosa (SG), we studied the serotonin (5-HT)- and noradrenaline
      (NA)-mediated inhibition of glutamate-mediated EPSCs evoked from primary afferent
      stimulation. 2. The frequency of spontaneous EPSPs was reduced by 5-HT and NA. 3.
      The inhibition of EPSCs caused by 5-HT was mediated by the 5-HT1D receptor
      subtype, since the 5-HT1D agonist, sumatriptan (1 microM), was effective. 4. NA
      and the alpha 2-agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6
      quinoxalinamine (UK 14304), decreased the EPSCs and this inhibition was blocked
      by the alpha 2-antagonists, idazoxan (1 microM) and yohimbine (1 microM). 5. The
      5-HT-releasing agent, fenfluramine (10 microM), and the Na-releasing agent,
      amphetamine (1 microM), also depressed EPSCs. Pretreatment of slices with the 5
      HT-depleting agent, p-chloro-amphetamine (10 microM), attenuated the inhibition
      of fenfluramine but failed to antagonize the effects of exogenously applied 5-HT.
      6. These in vitro results suggest that presynaptic inhibition of glutamate
      release from primary afferents can provide another mechanism to explain the
      antinociceptive effects of 5-HT and NA obtained in vivo.

PMID- 9011610
TI  - Effects of cytochalasin treatment on short-term synaptic plasticity at developing
      neuromuscular junctions in frogs.
AB  - 1. The role of actin microfilaments in synaptic transmission was tested by
      monitoring spontaneous and evoked transmitter release from developing
      neuromuscular synapses in Xenopus nerve-muscle cultures, using whole-cell
      recording of synaptic currents in the absence and presence of microfilament
      disrupting agents cytochalasins B and D. 2. Treatment with cytochalasins resulted
      in disruption of microfilament networks in the growth cone and the presynaptic
      nerve terminal of spinal neurons in Xenopus nerve-muscle cultures, as revealed by
      rhodamine-phalloidin staining. 3. The same cytochalasin treatment did not
      significantly affect the spontaneous or evoked synaptic currents during low
      frequency stimulation at 0.05 Hz in these Xenopus cultures. Synaptic depression
      induced by high-frequency (5 Hz) stimulation, however, was reduced by this
      treatment. Paired-pulse facilitation for short interpulse intervals was also
      increased by the treatment. 4. These results indicate that disruption of
      microfilaments alters short-term changes in transmitter release induced by
      repetitive activity, without affecting normal synaptic transmission at low
      frequency. 5. Our results support the notion that actin microfilaments impose a
      barrier for mobilization of synaptic vesicles from the reserve pool, but do not
      affect the exocytosis of immediately available synaptic vesicles at the active
      zone.

PMID- 9011611
TI  - Evidence for cutaneous and corticospinal modulation of presynaptic inhibition of
      Ia afferents from the human lower limb.
AB  - 1. Presynaptic inhibition of soleus muscle Ia afferent fibres, produced by
      stimulation of group I afferents in the common peroneal nerve, was assessed from
      changes in the H reflex at long conditioning intervals, in six normal subjects.
      2. Stimulation of the ipsilateral sural nerve at the malleolus, just before
      stimulation of the common peroneal nerve at the head of the fibula, decreased the
      presynaptic inhibition. This effect was strongest during voluntary plantar
      flexion and weaker during dorsiflexion or at rest. 3. Stimulation of other
      cutaneous nerve branches serving the dorsum of the ipsilateral foot, and also the
      contralateral sural nerve, decreased presynaptic inhibition. Adequate stimulation
      of low threshold cutaneous mechanoreceptors by light brushing of both distal
      dorsal and plantar surfaces of the ipsilateral foot decreased presynaptic
      inhibition. 4. Stimulation of the ipsilateral plantar nerves increased
      presynaptic inhibition, but this action is attributed to activation of group I
      afferents from the intrinsic muscles of the foot. 5. Transcranial magnetic
      stimulation of the lower limb area of the contralateral motor cortex decreased
      presynaptic inhibition. This effect was strongest during voluntary plantar
      flexion and weaker during dorsiflexion or at rest. 6. The actions of cutaneous
      and corticospinal pathways completely occluded each other. However, when both
      effects were adjusted to be liminal, a spatial facilitation between them was
      observed. 7. It is concluded that in man, as in the cat, cutaneous and
      corticospinal axons converge on interneurones that inhibit the machinery of
      presynaptic inhibition of group Ia afferents. These actions may be responsible
      for the modulation of presynaptic inhibition which has been observed to precede
      and accompany a wide range of human movements.

PMID- 9011612
TI  - Hypothalamic interaction between macrophage inflammatory protein-1 alpha (MIP-1
      alpha) and MIP-1 beta in rats: a new level for fever control?
AB  - 1. The microinjection of macrophage inflammatory protein-1 (MIP-1 alpha; 5.0 and
      25 pg) into the anterior hypothalamic, preoptic area (AHPOA) induced a slow
      onset; monophasic fever in rats that persisted for a long period. Microinjection
      of 25 pg MIP-1 beta into the AHPOA induced a fever of rapid onset, whereas 5.0 pg
      MIP-1 beta did not alter body temperature (Tb) significantly. When either MIP-1
      alpha or MIP-1 beta was heated to 70 degrees C for 30 min prior to their
      injection, no pyrexic response was produced. 2. The concurrent microinjection of
      25 pg MIP-1 alpha and 25 pg MIP-1 beta into the AHPOA attenuated the effects on
      Tb of either cytokine alone. However, pretreatment with either 5.0 pg MIP-1 beta
      or 5.0 pg MIP-1 alpha suppressed the febrile response induced by 25 pg MIP-1
      alpha or 25 pg MIP-1 beta, given at the same site, respectively. 3. The present
      experiments show that MIP-1 alpha and MIP-1 beta are active individually and
      possess distinct differences in their evocation of a febrile response. Further,
      our results suggest a functional antagonism between MIP-1 alpha and MIP-1 beta
      that could represent a new level in the development of fever.

PMID- 9011613
TI  - G(o)-2 protein mediates the reduction in Ca2+ currents by somatostatin in
      cultured ovine somatotrophs.
AB  - 1. Somatotroph-enriched cells (up to 85%) were obtained from ovine pituitary
      glands by means of collagenase dissociation and Percoll-gradient centrifugation.
      Further identification was based on the reduction in Ca2+ currents by 10 nM
      somatostatin (SRIF). 2. The whole-cell configuration of the patch-clamp technique
      was employed to study the membrane Ca2+ currents with K+ ions replaced by Cs+ and
      the addition of K+ and Na+ channel blockers in bath and pipette solutions. 3. A
      significant reduction in Ca2+ currents was obtained in response to local
      application of SRIF (10 nM) but vehicle application had no effect. 4.
      Intracellular dialysis of antibodies to alpha(o), alpha(i)-1-2, or alpha(i)-3
      subunits of G proteins into the cells via patch-clamp pipettes was confirmed by
      immunofluorescent staining of the antibodies. Antibody dialysis did not modify
      resting voltage-gated Ca2+ currents across the cell membrane. 5. Dialysis of anti
      alpha(o) antibodies significantly attenuated the reduction in Ca2+ currents that
      was obtained upon application of 10 or 100 nM SRIF. Dialysis of neither anti
      alpha(i)-1-2 nor anti-alpha(i)-3 antibodies diminished the effect of SRIF on Ca2+
      currents. 6. Intracellular dialysis of antisense oligonucleotides directed
      against the alpha(o) subunit mRNA (alpha(o) ASm, for alpha(o) common) or against
      the alpha(i)-3 subunit mRNA (alpha(i)-3 AS) blocked expression of alpha(o) or
      alpha(i)-3 subunits in the cells, respectively, as assessed by fluorescent
      staining with anti-alpha(o) or anti-alpha(i)-3 antibodies 48 h after dialysis. 7.
      Dialysis of alpha(o) ASm, but not alpha(i)-3 AS, significantly diminished the
      inhibitory effect of SRIF on Ca2+ currents. This effect of alpha(o) ASm dialysis
      occurred within 12 h after dialysis and reached a maximum at 48 h; partial
      recovery was seen at 72 h. 8. Antisense oligonucleotides specific for alpha(o)-1
      (alpha(o)-1 AS) or alpha(o)-2 (alpha(o)-2 AS) were dialysed into somatotrophs and
      only alpha(o)-2 AS significantly attenuated the inhibition of Ca2+ currents by
      SRIF. 9. We conclude that the G(o)-2 protein mediates the effect of SRIF on Ca2+
      currents in ovine somatotrophs in primary culture.

PMID- 9011614
TI  - Role of de novo protein synthesis and calmodulin in rapid activation of Na(+)-H+
      exchange of aldosterone in frog diluting segment.
AB  - 1. In the amphibian early distal tubule aldosterone activates the Na(+)-H+
      exchangers, resulting in an increase in intracellular pH (pHi). Since this
      activation is rapid (within 30 min), it may be mediated by either a genomic or
      non-genomic pathway. 2. pHi was measured in single microperfused early distal
      tubule segments using the fluorescent probe 2',7'-bis(carboxyethyl)-5,6
      carboxyfluorescein (BCECF). 3. A 30 min incubation in aldosterone increased both
      resting pHi and the setpoint of the Na(+-H+ exchanger. These changes were
      prevented by the mineralocorticoid receptor antagonist, spironolactone. 4.
      Actinomycin D and cycloheximide, inhibitors of transcription and translation,
      respectively, were without effect on resting pHi, but inhibited activation of the
      Na(+)-H+ exchanger by aldosterone. 5. The effect of aldosterone upon pHi and
      setpoint was also prevented by the calcium-calmodulin antagonist, W-7. 6. These
      results indicate that, although the response to aldosterone is rapid, aldosterone
      binds to a specific mineralocorticoid receptor which then triggers gene
      activation followed by de novo protein synthesis. Furthermore, since calmodulin
      is a known activator of the Na(+)-H+ exchanger, and the response is inhibited by
      W-7, it is suggested that this protein may be calmodulin.

PMID- 9011615
TI  - Influence of atrial natriuretic factor on fluid efflux from the splenic
      circulation of the rat.
AB  - 1. Atrial natriuretic factor (ANF) causes a reduction in plasma volume that is
      abolished by splenectomy. Experiments were conceived to investigate whether ANF
      acts within the spleen to increase efflux of fluid from the intravascular to the
      extravascular space. 2. ANF, infused into the splenic artery of anaesthetized
      rats at rates of 1, 5 and 20 ng min -1, caused a dose-dependent increase in the
      arteriovenous difference in haematocrit as blood flowed through the spleen (basal
      difference, 0.18 +/- 0.10%; difference after 10 min at 20 ng min -1 ANF, 1.5 +/-
      0.18%; n = 6). There was no such change in plasma protein concentration. 3. ANF
      (20 ng min -1) did not alter splenic arterial blood flow. However, splenic venous
      blood flow fell so that the arteriovenous difference increased significantly
      (basal difference, 0.34 +/- 0.19 ml min -1; difference at 60 min, 1.1 +/- 0.20 ml
      min-1, n = 7). There was no change in mean arterial pressure. 4. These data
      confirm our hypothesis that ANF acts within the spleen to increase fluid efflux
      from the intravascular to the extravascular space. Since there is no change in
      total splenic blood flow, we propose that the effects of ANF are mediated by
      dilatation of the splenic afferent arterioles and constriction of the efferent
      venules, thus increasing filtration pressure.

PMID- 9011616
TI  - Possible involvement of glucocorticoids in the modulation of interleukin-1
      induced cardiovascular responses in rats.
AB  - 1. In freely moving rats, we investigated whether glucocorticoids modulate the
      cardiovascular responses to intraperitoneal (I.P.) injection of interleukin-1
      beta (IL-1 beta). 2. A lower dose of IL-1 beta (1 microgram kg-1, I.P.) induced
      monophasic increases, and a higher dose (10 micrograms kg-1, I.P.) induced
      biphasic increases in both blood pressure and heart rate. Plasma concentration of
      corticosterone increased significantly after injection of IL-1 beta (10
      micrograms kg-1). 3. Systemic pretreatment with an exogenous glucocorticoid,
      dexamethasone (DEX; 0.5 mg kg-1) reduced the monophasic pressor response, the
      first phase of the biphasic pressor response and also the initial tachycardia. By
      contrast, the second phase of the biphasic pressor response was enhanced. 4.
      After bilateral adrenalectomy, the IL-1 beta (10 micrograms kg-1)-induced pressor
      effect was reduced; it was restored by treatment with DEX (0.5 mg kg-1). The
      heart rate response was enhanced in adrenalectomized (ADX) rats; this enhancement
      was attenuated by DEX. 5. IL-1 beta (10 micrograms kg-1)-induced increases in
      plasma noradrenaline (NA) were suppressed in intact rats pretreated with DEX (0.5
      mg kg-1). The IL-1 beta-induced NA response was greater in ADX rats than in sham
      ADX rats. 6. We suggest that glucocorticoids are an important modulator of
      cardiovascular responses induced in rats by systemically administered IL-1 beta.

PMID- 9011617
TI  - Inspiratory drive and phase duration during carotid chemoreceptor stimulation in
      the cat: medullary neurone correlations.
AB  - 1. This study addressed the hypothesis that there is a parallel processing of
      input from carotid chemoreceptors to brainstem neurones involved in inspiratory
      phase timing and control of inspiratory motor output amplitude. Data were from
      fifteen anaesthetized, bilaterally vagotomized, paralysed, artificially
      ventilated cats. Carotid chemoreceptors were stimulated by close arterial
      injection of 200 microliters of CO2-saturated saline solution. 2. Planar arrays
      of tungsten microelectrodes were used to monitor simultaneously up to twenty-two
      neurones in the nucleus tractus solitarii (NTS) and ventral respiratory group
      (VRG). Spike trains were analysed with two statistical tests of respiratory
      modulation, cycle-triggered histograms, peristimulus-time histograms, cumulative
      sum histograms and cross-correlograms. 3. In NTS, 16 of 26 neurones with
      respiratory and 12 of 27 without respiratory modulation changed firing rate
      during carotid chemoreceptor stimulation. In the VRG 72 of 112 respiratory and 14
      of 48 non-respiratory neurones changed firing rate during stimulation. 4. The
      spike trains of 85 of 1276 pairs (6.7%) of cells exhibited short time scale
      correlations indicative of paucisynaptic interactions. Ten pairs of neurones were
      each composed of a rostral VRG phasic inspiratory neurone that responded to
      carotid chemoreceptor stimulation with a decline in firing rate and a caudal VRG
      phasic inspiratory neurone that increased its firing rate. Cross-correlograms
      from two of the pairs had features consistent with excitation of the caudal
      neurones by the rostral cells. A decrease in the duration of activity of the
      rostral VRG neurones was paralleled by the decrease in inspiratory time of
      phrenic nerve activity. Caudal VRG inspiratory neurones increased their activity
      as phrenic amplitude increased. Spike-triggered averages of all four neurones
      indicated post-spike facilitation of phrenic motoneurones. 5. The results support
      the hypothesis that unilateral stimulation of carotid chemoreceptors results in
      parallel actions. (a) Inhibition of rostral VRG I-Driver neurones decreases
      inspiratory duration. (b) Concurrent excitation of premotor VRG and dorsal
      respiratory group inspiratory neurones increases inspiratory drive to phrenic
      motoneurones. Other data suggest that responsive ipsilateral neurones act to
      regulate contralateral neurones.

PMID- 9011618
TI  - Effect of CO2 on the metabolic and ventilatory responses to ambient temperature
      in conscious adult and newborn rats.
AB  - 1. In newborn and adult rats, hypoxia decreases metabolic rate, especially at low
      ambient temperatures (Ta). We examined whether a similar effect can occur during
      hypercapnia. 2. We measured metabolism (oxygen consumption, Vo2, open flow
      through method), and expiratory ventilation (VE; barometric method (adults),
      airflow plethysmograph (newborns)) in air and 2% or 5% CO2 in normoxia. 3. In
      adults, Vo2 was higher at Ta = 10 degrees C than 25 degrees C. At each Ta, CO2
      breathing did not change Vo2, but increased VE, less at 10 degrees C (up to
      +100%) than at 25 degrees C (+161%). Blood pressure was maintained at both values
      of Ta and CO2, while pulse rate and body temperature were decreased in 5% CO2 at
      10 degrees C. 4. In newborns, the metabolic response to lowering Ta (from 40 to
      20 degrees C) much depended on behavioural responses, being larger in groups of
      two or four pups than in individual animals. In no case did CO2 influence the
      response. VE increased during 5% CO2 exposure, more so at Ta = 33 percent C
      (+69%) than at 25 degrees C (+49%). 5. In both adults and newborns, hypoxia (10%
      O2) always decreased metabolic rate. 6. We conclude that hypercapnia has no
      appreciable effects on metabolic rate in rats (both newborns and adults) even at
      low Ta, a result quite different from the hypometabolic response to hypoxia.

PMID- 9011619
TI  - Excitatory drive to the alpha-motoneuron pool during a fatiguing submaximal
      contraction in man.
AB  - 1. This study was undertaken to examine changes of excitatory drive to the
      triceps surae alpha-motoneuron pool during fatiguing submaximal isometric
      contractions in man. Eight healthy subjects maintained isometric plantar flexions
      at 30 percent of maximum voluntary contraction (MVC) until the limit of endurance
      (range, 6-9 min). 2. Excitability of the alpha-motoneuron pool to Ia afferent
      stimulation (H reflex), electromyograms (EMG) and maximum compound motor unit
      action potentials (Mmax) from the lateral (LG) and medial heads (MG) of the
      gastrocnemius as well as from the soleus muscle (Sol) were recorded throughout
      the contraction. Superimposed maximum twitch torques (twitch occlusion) and
      isometric torque fluctuations (tremor) were also recorded as indirect measures of
      excitatory drive. 3. H reflexes were studied at different levels of underlying
      voluntary contraction to assess the relationship between H reflex amplitude and
      excitatory drive. With increasing levels of underlying contraction up to MVC,
      superimposed H reflex amplitude increased for LG in six subjects, for MG in all
      eight and for Sol in five. In the remaining cases, H reflex amplitude first
      increased and then plateaued between 30-50% of MVC. 4. H/Mmax ratios increased
      during fatigue in those muscles that showed an H reflex amplitude increase with
      high levels of underlying contraction. In these cases, LG and MG H/Mmax increased
      significantly after about 50 and 20% of endurance time onward, respectively,
      whereas Sol H/Mmax demonstrated a significant increase up to 40% of endurance
      time. 5. EMG root mean square (r.m.s.) increased linearly throughout the
      contraction for all three muscles, while tremor r.m.s. increased in a non-linear
      way, with a steeper increase from 60% of endurance time onward. Superimposed
      twitch amplitude decreased significantly from 25% of endurance time onward. 6. It
      is concluded that during fatiguing isometric contractions at 30% of MVC, the
      excitatory drive to the triceps surae alpha-motoneuron pool increases. This is
      thought to be a compensatory mechanism to facilitate recruitment of new,
      unfatigued motor units (MUs), and/or to increase MU firing rates. The facts that
      the twitch is not abolished at endurance limit and that the EMG does not attain
      its unfatigued MVC level are strong indications that central fatigue occurred
      during the sustained submaximal contraction.

PMID- 9011620
TI  - Differences between outward currents of human atrial and subepicardial
      ventricular myocytes.
AB  - 1. Outward currents were studied in myocytes isolated from human atrial and
      subepicardial ventricular myocardium using the whole-cell voltage clamp technique
      at 22 degrees C. The Na+ current was inactivated with prepulses to -40 mV and the
      Ca2+ current was eliminated by both reducing extracellular [Ca2+] to 0.5 mM and
      addition of 100 microM CdCl2 to the bath solution. 2. In human myocytes, three
      different outward currents were observed. A slowly inactivating sustained outward
      current, I(so), was found in atrial but not ventricular myocytes. A rapidly
      inactivating outward current, I(to), of similar current density was observed in
      cells from the two tissues. An additional uncharacterized non-inactivating
      background current of similar size was observed in atrial and in ventricular
      myocytes. 3. I(to) and I(so) could be differentiated in atrial myocytes by their
      different kinetics and potential dependence of inactivation, and their different
      sensitivities to block by 4-amino-pyridine, suggesting that two individual
      channel types were involved. 4. In atrial cells, inactivation of I(to) was more
      rapid and steady-state inactivation occurred at more negative membrane potentials
      than in ventricular cells. Furthermore, the recovery of I(to) from inactivation
      was slower and without overshoot in atrial myocytes. In addition, 4-aminopyridine
      induced block of I(to) was more efficient in atrial than in ventricular cells.
      These observations suggest that the channels responsible for atrial and
      ventricular I(to) were not identical. 5. We conclude that the differences in
      outward currents substantially contribute to the particular shapes of human
      atrial and ventricular action potentials. The existence of I(so) in atrial cells
      only provides a clinically interesting target for anti-arrhythmic drug action,
      since blockers of I(so) would selectively prolong the atrial refractory period,
      leaving ventricular refractoriness unaltered.

PMID- 9011621
TI  - Control of ion flux and selectivity by negatively charged residues in the outer
      mouth of rat sodium channels.
AB  - 1. The sodium channel has a ring of negatively charged amino acids on its
      external face. This common structural feature of cation-selective channels has
      been proposed to optimize conduction by electrostatic attraction of permeant
      cations into the channel mouth. We tested this idea by mutagenesis of mu1 rat
      skeletal sodium channels expressed in Xenopus oocytes. 2. Replacement of the
      external glutamate residue in domain II by cysteine reduces sodium current by
      decreasing single-channel conductance. While this effect can be reversed by the
      negatively charged sulfhydryl modifying reagent methanethiosulphonate
      ethylsulphonate (MTSES), the flux saturation behaviour cannot be rationalized
      simply by changes in the surface charge. 3. The analogous mutations in domains I,
      III and IV affect not only conductance but also selectivity. These changes in
      selectivity are only partially reversed by exposure to MTSES. 4. Our findings
      necessitate revision of prevailing concepts regarding the role of superficial
      negatively charged residues in the process of ion permeation. These residues do
      not act solely by electrostatic attraction of permeant ions, but instead may help
      to form ion-specific binding sites within the pore.

PMID- 9011622
TI  - Evidence against a contribution by Na(+)-Cl- cotransport to chloride accumulation
      in rat arterial smooth muscle.
AB  - 1. Chloride accumulation into rat saphenous arterial smooth muscle has been
      examined using chloride-sensitive microelectrodes, to assess the contribution of
      Na(+)-Cl-cotransport. 2. Bumetanide (10 microM) produced a fall in intracellular
      chloride ([Cl-]i), and a hyperpolarization of membrane potential (Em). However,
      [Cl-]i remained above the equilibrium level predicted from the membrane
      potential, indicating a residual accumulation. 3. Replacement of extracellular
      sodium with N-methyl-D-glucamine or choline caused a fall in [Cl-]i similar to
      that observed with bumetanide, but the hyperpolarization of Em was larger. In
      Na(+)-free media, bumetanide had no effect. [Cl-]i remained significantly above
      equilibrium. 4. In the presence of bumetanide, chlorothiazide produced a further
      dose-dependent fall in [Cl-]i, and hyperpolarization of Em. However, although [Cl
      ]i fell more than with bumetanide alone, it remained significantly above
      equilibrium. Metolazone was without effect at 100 microM. 5. In the presence of
      bumetanide, ethacrynic acid and N-ethyl maleimide caused a dose-dependent
      hyperpolarization of Em and a fall in [Cl-]i to equilibrium. 6. The third inward
      chloride pump in rat saphenous arterial smooth muscle appears not to be a form of
      Na(+)-Cl- cotransport. The potency series of thiazide diuretic action
      (acetazolamide > chlorothiazide > metolazone) differed significantly from that
      published for Na(+)-Cl- cotransport, and there is no sodium dependence.

PMID- 9011623
TI  - Kinetic evidence distinguishing volume-sensitive chloride current from other
      types in guinea-pig ventricular myocytes.
AB  - 1. Kinase-mediated chloride currents (ICl) in guinea-pig ventricular myocytes
      were activated by application of phorbol ester or forskolin, and compared with
      currents induced by hyposmotic swelling. Swelling-activated current was
      identified as ICl from changes in reversal potential, outward rectification and
      conductance when the Cl-gradient was modified. 2. Kinase-stimulated currents were
      relatively time and voltage independent, whereas hyposmotic swelling-stimulated
      (hyposmotic-stimulated) currents inactivated during 100 ms pulses to positive
      potentials. Forskolin stimulated time-independent ICl in myocytes with current
      unresponsive to hyposmotic superfusion, and superimposed a similar pedestal on
      time-dependent ICl in swollen myocytes. 3. Less negative holding potentials
      depressed hyposmotic-stimulated ICl tested at +80 mV; inhibition was half-maximal
      at -25 mV. Pulses from -80 to +80 mV inactivated up to 75% of ICl along a multi
      exponential time course; repolarization elicited inwardly developing tail
      currents whose time courses suggest complex gating. 4. Hyperpolarizations, after
      strongly-inactivating depolarizations, triggered reactivating tail currents whose
      amplitude and configuration were dependent on voltage and Cl-gradients; tails
      were large and inwardly developing at potentials negative to the calculated Cl
      equilibrium potential (ECl), small and outwardly developing at potentials
      positive to ECl, and time independent near ECl. 5. These results suggest that the
      volume-sensitive Cl- channels investigated here are distinct from other Cl-
      channels in guinea-pig ventricular myocytes. However, their voltage-dependent
      properties strongly resemble those of volume-sensitive Cl- channels in certain
      epithelial cells.

PMID- 9011626
TI  - Structural improvement of an electronic pantograph stylus assembly.

PMID- 9011624
TI  - Characterization of a beta-adrenergically inhibited K+ current in rat cardiac
      ventricular cells.
AB  - 1. The electrophysiological properties and beta-adrenergic regulation of a non
      inactivating K+ current were studied using the whole-cell patch-clamp technique
      (22 +/- 2 degrees C) in adult rat ventricular cells. 2. In the presence of 4
      aminopyridine, an inhibitor of the rapidly inactivating current, the
      depolarization-activated current consisted only of a slowly decaying outward
      current (IK). The presence of a non-inactivating current (ISS) was revealed when
      analysing inactivation curves. 3. IK and ISS were both sensitive to 50 mM
      tetraethylammonium and 10 mM 4-aminopyridine inhibition. IK was totally blocked
      by 100 microM clofilium, while ISS was not inhibited but rather enhanced by this
      class III anti-arrhythmic agent. 4. Unlike IK, ISS was only slightly decreased by
      depolarizing prepulses and it did not show time-dependent inactivation when
      measured during 500 ms depolarizations. 5. ISS was decreased by the beta
      adrenergic agonist isoprenaline (1 microM). Forskolin (10 microM) mimicked the
      effects of isoprenaline. The non-specific beta-adrenergic antagonist, propranolol
      (3 microM), and a specific beta 1-adrenergic antagonist, CGP 20712A (0.3 microM),
      both prevented the effects of isoprenaline. Cell perfusion with 100 microM PKI6
      22, a peptide inhibitor of the cyclic AMP-dependent protein kinase, reduced or
      abolished the effects of isoprenaline. 6. The dose-response curve for the
      inhibition of ISS by isoprenaline was positioned to the left of that for the
      calcium current. The threshold dose and the dose giving 50% of the maximal effect
      were, respectively, 0.1 and 0.21 nM for ISS and 1 and 4.3 nM for ICa. 7. In view
      of the high sensitivity of ISS to isoprenaline, its possible physiological effect
      was evaluated on action potential duration during beta-adrenergic stimulation. At
      1 nM, a concentration that did not increase ICa, isoprenaline induced a
      significant prolongation of action potential duration as a consequence of ISS
      inhibition. With 1 microM isoprenaline, the action potential was further
      prolonged, due largely to an evoked increase in ICa. 8. In conclusion, a K+
      current displaying a weak voltage-dependent inactivation is present in rat
      ventricular cells. It is inhibited by stimulation of beta 1-adrenergic receptors
      and is highly sensitive to phosphorylation by protein kinase A. This current may
      play an important role in the neuromodulation of excitation-contraction coupling.

PMID- 9011627
TI  - Nonhuman Primate Models for AIDS VIII. Proceedings of a meeting. Monterey,
      California, November 5-8, 1995.

PMID- 9011625
TI  - Cross-talk between ATP-regulated K+ channels and Na+ transport via cellular
      metabolism in frog skin principal cells.
AB  - Isolated frog skin epithelium, mounted in an Ussing chamber and bathed in
      standard NaCl Ringer solution, recycles K+ across the basolateral membrane of
      principal cells through an inward-rectifier K+ channel (Kir) operating in
      parallel with a Na+-K+-ATPase pump. Here we report on the metabolic control of
      the Kir channel using patch clamping, short-circuit current measurement and
      enzymatic determination of cellular (ATP (ATPi). 2. The constitutively active Kir
      channel in the basolateral membrane has the characteristics of an ATP-regulated
      K+ channel and is now classed as a KATP channel. In excised inside-out patches
      the open probability (Po) of KATP channels was reduced by ATPi with half-maximum
      inhibition at an ATPi concentration of 50 microM. 3. ATPi measured (under normal
      Na+ transport conditions) with luciferin-luciferase was 1.50 +/- 0.23 mM (mean +/
      S.E.M.; range, 0.4-3.3 mM n = 11). Thus the KATP channel would be expected to be
      inactive in intact cells if ATPi was the sole regulator of channel activity. KATP
      channels which were inactivated by 1 mM ATPi in excised patches could be
      reactivated by addition of 100 microM ADP on the cytosolic side. When added
      alone, ADP blocks this channel with half-maximal inhibition at [ADPi] > 5 mM. 4.
      Sulphonylureas inhibit single KATP channels in cell-attached patches as well as
      the total basolateral K+ current measured in frog skin epithelia perforated with
      nystatin on the apical side. 5. Na+-K+-ATPase activity is a major determinant of
      cytosolic ATP. Blocking the pump activity with ouabain produced a time-dependent
      increase in ATPi and reduced the open probability of KATP channels in cell
      attached membranes. 6. We conclude that the ratio of ATP/ADP is an important
      metabolic coupling factor between the rate of Na+-K+ pumping and K+ recycling.

PMID- 9011628
TI  - Attenuated purine production during subsequent ischemia in preconditioned rabbit
      myocardium is unrelated to the mechanism of protection.
AB  - Preconditioned hearts release less purines during ischemia than virgin hearts.
      This study tested whether this reduced purine production is related to the
      mechanism of protection by ischemic preconditioning. Coronary effluent from
      isolated rabbit hearts was collected and purine (adenosine + inosine +
      hypoxanthine) levels were measured. All hearts underwent two cycles of 5 min
      global ischemia, each followed by 10 min reperfusion. In the first minute of
      reflow after the first ischemic period untreated hearts released 155 +/- 14 nmol
      purines per g wet weight, but only 104 +/- 16 nmol/g following the second bout of
      ischemia (P < 0.05). Thus, preconditioned hearts released less purines during
      ischemia. When 8-(p-sulfophenyl)theophylline (100 microM), which prevents the
      infarct size-limiting effect of ischemic preconditioning by blocking adenosine
      receptors was present in the perfusate, the pattern of purine release was not
      altered (151 +/- 13 nmol/g during the first minute after the first 5-min ischemic
      episode dropping to 117 +/- 6 nmol/g after the second ischemic period P < 0.05).
      Furthermore, pharmacological preconditioning with 5 min exposure of the heart to
      either adenosine (10 microM) or phenylephrine (0.1 microM) 15 min prior to the
      first ischemia did not affect purine release during early reperfusion after
      either the first (144 +/- 16 nmol/g and 153 +/- 12 nmol/g, respectively) or
      second (84 +/- 12 nmol/g and 111 +/- 9 nmol/g, respectively) bout of ischemia.
      Since the attenuated purine release was apparently unaffected by the presence or
      absence of a protected state, we conclude that this pattern is unrelated to the
      mechanism by which preconditioning protects the heart.

PMID- 9011629
TI  - The presence and partitioning of calcium binding proteins in hepatic and cardiac
      nuclei.
AB  - Calcium is an important signal in key nuclear events, including cell cycle timing
      regulation of gene expression and activation of nuclear kinases and phosphatases.
      It is therefore important to identify calcium binding proteins in the nucleus
      which may play roles in these functions, and to determine whether these proteins
      are located in the nuclear envelope or in the nucleoplasm. Rat hepatic and pig
      cardiac nuclei were isolated and treated with a high salt solution to separate
      nucleoplasmic proteins from those associated with the nuclear envelope. The
      presence of calcium binding proteins was then revealed by Stains-All, staining of
      electrophoretic gels and 45Ca2+ overlays of Western blots. Four major calcium
      binding proteins were putatively identified in the pig cardiac nuclei, and
      another three in the rat hepatic nuclei. Proteins of 110, 93 and 35 kDa were
      observed in the pig cardiac nuclear envelope fraction, and another of 55 kDa in
      the pig cardiac high salt fraction. A 93-kDa protein was observed in the rat
      hepatic nuclear envelope fraction, and others of 120 and 110 kDa in the rat
      hepatic high salt fraction. A tentative identification has been made of the 93
      kDa protein in each tissue type as calnexin, and of the cardiac 55 kDa protein as
      calsequestrin. This study, therefore, has putatively identified for the first
      time the presence of several calcium binding proteins which have distinct
      partitioning within hepatic and cardiac nuclei. This localization may play an
      important functional role within the nuclei.

PMID- 9011630
TI  - Constitutive expression of HSP 72 in swine heart.
AB  - Stress-induced regulation of the 72 kD heat shock protein (HSP 72), the major
      stress inducible protein in mammalian cells, is mediated by the activation and
      binding of a heat shock transcription factor (HSF) to a specific sequence in the
      5' region of the promoter termed the heat shock element (HSE). In agreement with
      this regulation, HSP 72 is absent in most cells under unstressed conditions but
      is rapidly synthesized following exposure to protein damaging stressors. An
      exception is the skeletal muscle, where HSP 72 is constitutively expressed in
      muscles that express the beta myosin heavy chain (beta-MHC) protein. Since beta
      MHC is also expressed in the ventricles of large mammals, we have examined if HSP
      72 was also constitutively expressed in beta-MHC positive hearts. Chambers of the
      heart muscle from Yorkshire swine were examined for alpha-MHC, beta-MHC and HSP
      72 content. HSF:HSE activation was also assessed by gel shift analyses. In the
      swine heart, atria and ventricles differed in their alpha-MHC and beta-MHC
      protein content but all expressed a high HSP 72 content. Gel shift analyses
      demonstrated no HSF:HSE binding in extracts from unstressed swine hearts. These
      results indicate that HSP 72 is constitutively expressed in all portions of the
      swine heart and this expression may not be dependent on an HSF:HSE interaction.

PMID- 9011631
TI  - Mathematical modeling of relations between the kinetics of free intracellular
      calcium and mechanical function of myocardium.
AB  - The paper describes a mathematical model of cardiac muscle contraction based on
      the assumption of two types of co-operativity which control the formation of
      calcium-troponin complexes and on a simplified scheme of free intracellular
      calcium kinetics. Calcium transients are shown to be different in isotonic and
      isometric conditions, being dependent on initial muscle length as well. Numerical
      experiments and analysis of the model suggest that calcium uptake by the
      sarcoplasmic reticulum slows down with an increase in the intracellular
      concentration of free calcium. This suggestion enables the model to explain the
      disappearance of load-dependent relaxation observed experimentally at cardiac
      hypertrophy.

PMID- 9011632
TI  - Aging-induced up-regulation of nuclear binding activities of oxidative stress
      responsive NF-kB transcription factor in mouse cardiac muscle.
AB  - The accumulation of lipofuscin to cardiomyocytes is a classical parameter of
      aging and is believed to reflect oxidative stress. NF-kB transcription factor
      complex is one of the cellular sensors which responds to oxidative stress and
      regulates gene expression. Our purpose was to study whether aging affects the
      level and distribution of DNA binding activities of NF-kB transcription factors
      both in cardiac sarcoplasm and nuclear extracts. We used electrophoretic mobility
      shift assays (EMSA) to characterize the DNA binding activities of NF-kB and two
      other transcription factors. AP-1 and Sp-1, in the myocardium of 4 months and 24
      months old male and female NMRI-mice. The protein levels of p50, p52, and p65
      components of NF-kB-complex and an inhibitory IkB-alpha/MAD-3 were assayed with
      Western blots. Surprisingly, aging upregulated by 123% the nuclear NF-kB binding
      activity in the male and female mice. The sarcoplasmic NF-kB activity, activated
      by deoxycholate, did not show any change during aging. Aging-induced increase in
      nuclear NF-kB protein-DNA binding activity was observed both by gel retardation
      and UV-crosslinking assays. In immunoblotting, the level of p52 component but not
      those of p50 and p65 components of NF-kB-complex was slightly increased in
      nuclear fractions. Aging did not affect the sarcoplasmic levels of p50, p52, and
      p65 proteins. Supershift EMSA assays showed that the nuclear NF-kB complex
      contained p50, p52, and p65 components. The level of inhibitory IkB-alpha/MAD-3
      protein was unaffected by aging both in nuclear and sarcoplasmic fractions. Aging
      down-regulated the nuclear Sp-1 binding activities but did not affect AP-1
      binding activities. Statistically significant sex-related differences did not
      appear in the aging responses of transcription factors. These results indicate
      that NF-kB transcription factor pathway is activated during aging in cardiac
      muscle and could be the signaling route regulating gene expression. However, the
      activation mechanism of NF-kB during aging whether oxidative stress responsive or
      not in vivo needs further studies.

PMID- 9011633
TI  - The angiotensin type 2 receptor mediates RNA synthesis in A10 vascular smooth
      muscle cells.
AB  - This study was designed to define more precisely the relationship between
      specific angiotensin receptors and the growth of vascular smooth muscle cells in
      response to angiotensin II. These experiments employed quiescent A10 cells which
      were characterized as smooth muscle by the expression of specific contractlle
      proteins. Cell growth was monitored by measuring the incorporation of metabolic
      precursors into RNA or DNA. The treatment of A10 cells with angiotensin II (1
      microM) stimulated a hypertrophic response as indicated by an increase in RNA
      synthesis and protooncogene expression in the absence of DNA synthesis. This
      increase in RNA synthesis could be blocked by PD123319, an AT2 antagonist, but
      not by losartan, an AT1 antagonist. RT-PCR analysis demonstrated that quiescent
      A10 cells express only the AT2 receptor while proliferating A10 cells express the
      AT1a and AT1b receptors in addition to the AT2 receptor. In addition, induction
      of AT2 receptor-mediated RNA synthesis was prevented by indomethacin, a
      cyclooxygenase inhibitor. These studies therefore support a direct connection
      between the AT2 receptor and smooth muscle growth that is mediated, in part, by
      prostaglandin synthesis.

PMID- 9011634
TI  - Regression of hypertrophy after myocardial infarction is produced by the chronic
      blockade of angiotensin type 1 receptor in rats.
AB  - The efficacy of angiotensin converting enzyme (ACE) inhibitors is well known to
      prevent the formation of angiotensin II (Ang II) by these agents. The objective
      of the present study was to evaluate the hemodynamic, biochemical, and
      morphological responses to Ang II receptor blockade with E-4177, 3-[(2'
      carboxybiphenyl-4-yl) methyl]-2-cyclopropyl-7-methyl 3H-imidazol[4,5-b] pyridine,
      in rats with a healing myocardial infarction that had been induced by the
      surgical occlusion of the left main coronary artery. The left ventricular weight
      increased 8 and 12 weeks after infarction in comparison to that in sham-operated
      rats. Among the rats with experimental infarction, treatment with E-4177
      significantly decreased the left ventricular weight. Although the infarct size
      was not affected by E-4177, its administration ameliorated the elevated end
      diastolic pressure and reduced the systolic pressure. The effects of this agent
      on the levels of Ang II type 1 (AT1) receptor mRNA and ACe mRNA were evaluated in
      the non-infarcted myocardium by reverse transcriptase polymerase chain reaction
      and binding assays. Treatment with E-4177 reduced both the elevated AT1 mRNA and
      the number of Ang II receptors, but not the ACE mRNA or ACE activity. While the
      receptor affinity remained unchanged with this agent, the collagen concentration
      was decreased. On the other hand, the depressed Na+/Ca2+ exchange activity was
      restored in the non-infarcted myocardium at 8 and 12 weeks after injury to the
      level seen in the sham-operated rats. These findings suggest that the AT1
      receptor antagonist, E-4177, has a beneficial effect on the hemodynamics in spite
      of the lack of any improvement in the infarct size. These observations may be
      partly attributed to the prevention of angiotensin II formation during the period
      of post-infarction healing.

PMID- 9011635
TI  - The role of the rate of vascular collapse in ischemia-induced acute contractile
      failure and decreased diastolic stiffness.
AB  - We investigated the contribution of the rate of vascular collapse to the early
      contractile failure and decreased diastolic stiffness induced by ischemia.
      Isolated rat hearts (n = 8/group), perfused at 37 degrees C with blood through a
      roller pump and paced at 320 beats/min, were subjected to global ischemia either
      by switching off the roller pump (slow vascular collapse-group 1) or by reversing
      the direction of the roller pump for 5 s prior to switch-off (rapid vascular
      collapse-group 2). In group 1, residual coronary pressure declined progressively
      over the first 20 s of ischemia whereas in group 2 the pressure had fallen to
      zero within 2 s. The profile of ischemia-induced contractile failure was however,
      similar in both groups. Thus, after 2 s of ischemia, when residual perfusion
      pressure had declined by only 10% in group 1 (60.0 +/- 0.0 to 54.9 +/- 0.8 mmHg)
      but was virtually non-existent in group 2 (60.0 +/- 0.0 to 0.4 +/- 12.7 mmHg),
      left ventricular developed pressure had fallen to a similar extent in both groups
      (86 +/- 2% and 84 +/- 3%, respectively). Curve-fitting analysis for individual
      hearts showed that the profile of contractile failure was described by a double
      exponential process that was not significantly affected by the rapid vascular
      collapse. Left ventricular end-diastolic pressure in group 1 hearts progressively
      declined over the first 20 s of ischemia, the profile paralleling that of the
      dissipation of perfusion pressure. In contrast, in group 2 hearts, left
      ventricular end-diastolic pressure rose rapidly and leaked at 5 s, a period that
      coincided with the reversed direction of the perfusion pump. Similarly, in a
      separate study, the analysis of ventricular diastolic stiffness (n = 6/group)
      showed a rapid decline during the first 20 s of ischemia: this decline could be
      inhibited by the use of rapid vascular collapse. In additional experiments,
      hearts (n = 8/group) were paced at 220, 320 or 420 beats/min and ischemia was
      induced by reversing (5 s) and then stopping the perfusion pump. Myocardial
      oxygen consumption increased in parallel with heart rate and was matched by
      commensurate increases in the rate of contractile failure. Curve-fitting analysis
      showed that slow stimulation rates (220 beats/ min) significantly delayed
      contractile failure during the first 60 s of ischemia (first time constant = 14.5
      +/- 4.1 s compared with 8.1 +/- 1.1 s at 320 beats/min and 6.3 +/- 1.1 s at 420
      beats/min; P < 0.05 in both instances). In conclusion, vascular collapse
      associated with ischemia may contribute to the initial decrease in ventricular
      diastolic stiffness; however, it does not play a major role in determining the
      rate of acute contractile failure. Metabolic processes as reflected by oxygen
      consumption do however, appear to be important.

PMID- 9011636
TI  - Dichotomy in the post-ischemic metabolic and functional recovery profiles of
      isolated blood-versus buffer-perfused heart.
AB  - There is evidence that buffer- and blood-perfused hearts differ in their
      postischemic functional recoveries. The present study was designed to: (i)
      compare ischemia-induced contracture and post-ischemic functional recovery, and
      (ii) investigate whether the recovery profiles were related to either the release
      of purines and norepinephrine or high-energy phosphate content. Rat hearts (n =
      8/group) were perfused at 37 degrees C with buffer (60 mmHg) or blood (60 mmHg
      from a support rat), made globally ischemic (15 min) and reperfused (15 min). The
      onset and severity of ischemic contracture were identical in both models [left
      ventricular end-diastolic pressure (LVEDP) at the end of 15 min ischemia was 30
      +/- 5 and 27 +/- 4 mmHg respectively; P = N.S.]. However, the rate and extent of
      post-ischemic left ventricular developed pressure (LVDP) differed considerably.
      Blood-perfused hearts exhibited an initial rapid and complete recovery of LVDP
      followed by a steady decline to approximately 60% of pre-ischemic values. Buffer
      perfused hearts recovered to only 80% after 5 min reperfusion and remained at
      this level for the duration of reperfusion LVEDP was higher in buffer-perfused
      than in blood-perfused hearts during the first 5 min of reperfusion; thereafter,
      LVEDP fell in buffer-perfused hearts to a level than was not significantly
      different from the observed in blood-perfused hearts. In buffer-perfused hearts,
      coronary flow recovered to 90% within 5 min and then remained constant; in blood
      perfused hearts flow recovered to 100% by 1 min and continued to rise to a
      maximum by 7 min (201 +/- 15%). This increase appeared to mirror the secondary
      decline in LVDP. During the first 4 min of reperfusion, in both preparations,
      venous norepinephrine increased to six- to nine-fold of pre-ischemic values and
      then fell rapidly to near control levels by 6-9 min. Total purine release was
      high in early reperfusion in both groups. At the end of 15 min reperfusion, the
      tissue adenylate pool was similar in both groups. This study demonstrates that
      the nature of the perfusate used for an isolated rat heart preparation: (i) does
      not appear to influence the severity of ischemic injury as assessed by ischemic
      contracture, but (ii) does influence the qualitative and quantitative
      characteristics of the temporal profile that describes the recovery of systolic
      and diastolic function during the first 15 min of reperfusion: and (iii) it has
      no effect upon the changes seen in a number of metabolic indices that are often
      used for the assessment of injury and protection.

PMID- 9011637
TI  - Effect of raised extracellular calcium on characteristics of the guinea-pig
      ventricular action potential.
AB  - The whole-cell patch-clamp method was used to investigate the role of Na/Ca
      exchange current (INa,Ca) in the shortening action of raised extracellular
      calcium on the ventricular action potential. Experiments were performed either
      using BAPTA to buffer intracellular calcium, or by replacing extracellular Na+
      with Li- to abolish INa,Ca. A blocker of Ik, compound II. was used to investigate
      whether changes in this current may also play a role. Raising extracellular
      calcium from 1.8 mM to 5.0 mM increased the amplitude of the action potential by
      8% and decreased its duration (at 90% repolarization, APD90) by 23%. Compound II
      increased APD90 by 40% and resulted in the appearance of early
      afterdepolarizations but did not affect the response to raised extracellular
      calcium. Intracellular BAPTA (20 mM) did not prevent the calcium-induced
      shortening but did abolish the initial rapid phase of repolarization and increase
      the inactivation time constant of Icsl recorded under voltage clamp. Replacement
      of extracellular Na+ with Li+ dramatically shortened the action potential and
      under these conditions raising extracellular calcium lengthened the action
      potential. Using a voltage-clamp protocol to mimic an action potential, whole
      cell current in the absence and in the presence of Li(+)-replacement was recorded
      in normal and raised extracellular calcium. The lithium-sensitive current was
      inward during the "plateau" and was reduced by raising extracellular calcium. The
      results do not support a role for Ik in mediating action potential shortening in
      raised extracellular calcium. It is suggested that a decrease in inward INa,Ca
      may be largely responsible, with a role for increased Icsl inactivation in the
      early part of the action potential.

PMID- 9011638
TI  - Alterations of expression and distribution of the Ca(2+)-storing proteins in
      endo/sarcoplasmic reticulum during differentiation of rat cardiomyocytes.
AB  - Calsequestrin (CS) is a Ca(2+)-storing protein present in the sarcoplasmic
      reticulum (SR) of muscle cells. Calreticulin (CR) is a functional homologue of CS
      in the endoplasmic reticulum (ER) of non-muscle cells. During skeletal muscle
      differentiation, the major Ca(2+)-storing protein switches from CR to CS. To
      study the regulation of CS and CR expression in cardiomyocytes and the
      morphological maturation of Ca(2+)-storing sites in the SR, we examined rat
      hearts at various developmental stages and cultured adult cardiomyocytes by
      Western blotting and immunocytochemical analyses. CR was expressed in 14-day-old
      fetal rat cardiomyocytes, but disappeared gradually by 1 week after birth. CR
      reappeared in dedifferentiated adult cardiomyocytes in long-term culture. On
      Western blots, the concentration of CS in the heart did not change during
      development. Immunostaining for CS in fetal or neonatal rat cardiomyocytes
      revealed as scattered dots. CS-positive structures increased with development,
      and the regular striated distribution of CS at Z lines was completed around 3
      weeks after birth. These results indicated that (1) CR expression is
      downregulated during cardiac differentiation and upregulated during
      dedifferentiation, and (2) maturation of SR involves the organization of CS
      positive structure after birth.

PMID- 9011639
TI  - Myocardial glycogen depletion cannot explain the cardioprotective effects of
      ischemic preconditioning in the rat heart.
AB  - The mechanism of ischemic preconditioning remains unknown. The role of glycogen
      depletion prior to prolonged ischemia was examined as a potential mechanism of
      ischemic preconditioning. The glycogen content of the rat heart varies in a 24-h
      rhythm. In a retrospective study, the relationships between the time of day the
      animals were sacrificed, pre-ischemic myocardial glycogen content, and post
      ischemic functional recovery were assessed in non-conditioned and ischemically
      preconditioned hearts. The analyses were performed on previously published data
      (Asimakis et al.. 1992, 1993). After an equilibration perfusion, isolated rat
      hearts were given 40 min of global ischemia followed by 30 min of reperfusion.
      Preconditioned hearts received 5 min of ischemia followed by a 5-min recovery
      period prior to the 40-min ischemic period. Some of the hearts were freeze
      clamped immediately prior to the 40-min ischemic period to determine pre-ischemic
      glycogen content. Pre-ischemic glycogen was higher in the morning than afternoon.
      The time of day correlated significantly with the pre-ischemic glycogen content
      of non-conditioned (r = 0.67; P < 0.005) and preconditioned (r = 0.79; P < 0.001)
      hearts. However, time of day did not correlate significantly with post-ischemic
      recovery of heart rate x developed pressure (HR x DP) on end-diastolic pressure
      (EDP) in either the non-conditioned or preconditioned hearts. The relationships
      were also assessed by subdividing the groups into either morning (a.m.) or
      afternoon (p.m.) hearts. The pre-ischemic glycogen content was lower in the non
      conditioned-p.m. (n = 5) hearts compared to the non-conditioned-a.m. (n = 10)
      hearts (67.6 +/- 9.0 nu 128.1 +/- 13.3 nmol glucose/mg protein P < 0.005).
      However, there were no significant differences between p.m. (n = 13) and a.m. (n
      = 9) non-conditioned hearts with respect to post-ischemic recovery of HR x DP
      (20.6 +/- 4 nu 12.0 +/- 4% of baseline, respectively, P = N.S.). In contrast,
      preconditioned-p.m. (n = 6) and -a.m. (n = 7) had pre-ischemic glycogen contents
      of 49.6 +/- 6 and 76.6 +/- 5.0 nmol glucose/mg protein, respectively. These
      glycogen values were not significantly different from the non-conditioned-p.m.
      hearts (67.6 nmol/mg protein). However, post-ischemic recovery of HR x DP in the
      preconditioned-p.m. (n = 5) and -a.m. (n = 6) hearts were 54.6 +/- 5 and 51.4 +/-
      8% of baseline, respectively (these values were significantly higher (P < 0.05)
      than the recovery for the non-conditioned-p.m. and -a.m. hearts). The results
      imply that the cardioprotection of ischemic preconditioning cannot be explained
      solely by myocardial glycogen depletion.

PMID- 9011640
TI  - In vivo colored microspheres in the isolated rat heart for use in NMR.
AB  - Myocardial perfusion measurement with colored microspheres may become an
      alternative for radioactive microsphere techniques. We use and validate a
      spectrophotometric method that has been previously established for large animals
      in the isolated perfused rat heart. The perfusion system was adapted for use in a
      NMR microscope. Hearts were perfused with constant coronary flow that was
      adjusted to a coronary perfusion pressure of 100 mmHg. Homogeneous coronary
      inflow of microspheres was represented by equal distribution of microspheres of
      two different colors after simultaneous injection. Mean regional myocardial blood
      flow was 17.76 +/- 5.01 ml/min/g, mean wet heart weight was 1.13 +/- 0.34 g and
      mean global flow was 20.06 +/- 0.60 ml/min. Heart rate was 296 +/- 8.9 beats/min
      and left ventricular pressure was similar 5 min before (149.1 +/- 14.27 mmHg) and
      after (147.1 +/- 13.49 mmHg) microsphere injection. Microspheres of four colors
      that were injected sequentially, at various coronary flows, demonstrated
      linearity and reproducibility of the technique. A cumulative use of less than 90
      000 microspheres showed no effect on hemodynamics especially on left ventricular
      pressure.

PMID- 9011642
TI  - The relation between cellular sodium, pH and volumes and the activity of Na/H
      antiport during hypothermic ischemia: multinuclear NMR studies of rat hearts.
AB  - The present study evaluates the activity of the Na/H antiport during cold
      ischemia and aims to determine its influence on cellular sodium. pH and volumes.
      Cellular parameters; volumes, sodium, pH and high energy phosphates, were
      measured by multinuclear NMR spectroscopy in rat hearts during 12 h of storage at
      4 degrees C and reperfusion, along with functional parameters. Cell volumes were
      measured by 1H and 59Co NMR using the extracellular marker cobalticyanide, pH and
      energetics by 31P NMR and sodium compartmental distribution by 23Na NMR
      spectroscopy using the shift reagent Dy(TTHA)-3. Three storage solutions were
      applied: Krebs-Henseleit (containing 144 mM sodium, KH), a solution supplemented
      with 0.20 mM amiloride (KH-ami) and a solution containing 23 mM sodium and 242 mM
      mannitol (KH-man). Inhibition of the Na/H antiport with amiloride reduced the
      cellular sodium accumulation by 56%. The end-ischemic concentrations were 45 mM
      (KH-ami) and 77 mM (KH). Amiloride also reduced the extent of cell swelling by
      53% from an end-ischemic volume of 3.56 ml/gdw (KH) to 2.97 ml/gdw (KH-ami),
      however cell swelling persisted in both groups at reperfusion (33% increase in
      cell water). The molar ratio of sodium and water cellular accumulation was
      constant: Na/H2O approximately 3.7 x 10(-3) throughout the whole storage period.
      Inhibition of the antiport was protective for the high energy phosphates during
      ischemia and reperfusion. In KH-ami the pH acidified after 6 h of storage to an
      end-ischemic value of 6.35 (pH = 6.50 in KH): this difference persisted after 60
      min of reperfusion, pH = 6.98 in KH-ami and pH = 7.1 in KH. Storage in the low
      sodium solution was disadvantageous for the high energy phosphates during
      ischemia and reperfusion with a recovery of pH to 6.92 when reperfused with KH.
      Hearts stored with amiloride or mannitol solution failed to resume contraction at
      reperfusion. It is concluded: (a) the antiport is active at 4 degrees C; (b)
      during ischemia it mediates sodium influx and contributes to cell swelling with
      minor effects on the cytosolic pH; (c) at reperfusion the antiport is active it
      participates in the extrusion of excess protons, but has a minor impact on sodium
      and water homeostasis; (d) inhibition of the antiport does not protect the
      cardiac muscle at low temperatures.

PMID- 9011643
TI  - Aspirin does not prevent the attenuation of myocardial stunning by the ACE
      inhibitor ramiprilat.
AB  - The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is
      prevented by cyclooxygenase inhibition with indomethacin. In the clinical setting
      of ischemia/reperfusion however, the cyclooxygenase inhibitor aspirin is widely
      used to prevent platelet aggregation. The present study therefore investigated
      whether aspirin in dosages sufficient to inhibit platelet aggregation interferes
      with the attenuation of myocardial stunning by ramiprilat. Fifteen dogs received
      either 1 mg/(kg.day) (group I, n = 7) or 10 mg/(kg.day) (group II, n = 8) aspirin
      orally for 1 week. Both dosages of aspirin inhibited ADP-induced platelet
      aggregation. The dogs were then anesthetized thoracotomized and subjected to 15
      min LCx-occlusion and 4 h reperfusion. Before LCx-occlusion, groups I and II
      received ramiprilat (20 micrograms/kg, i.v.). Systemic hemodynamics, posterior
      myocardial blood flow (PMBF, colored microspheres) and wall thickening (PWT,
      sonomicrometry) of these groups were measured and data compared to placebo
      controls (group III, n = 11) and dogs receiving only ramiprilat before LCx
      occlusion (group IV, n = 11). Four dogs received 10 mg/(kg.day) aspirin without
      ramiprilat (group V). Mean aortic pressure was kept constant by an intra-aortic
      balloon, and heart rate did not change. PMBF was not different between the five
      groups. Under control conditions and during myocardial ischemia PWT was also not
      different. At 4 h reperfusion PWT was still depressed in group III (-5 +/- 20% of
      control) and group V (-23 +/- 6%) whereas PWT recovered to the same extent in
      groups I (46 +/- 23%), II (50 +/- 15%) and IV (58 +/- 18%) (all P < 0.05 v groups
      III and V). The attenuation of myocardial stunning by the ACE inhibitor
      ramiprilat is not prevented by aspirin in dosages which are nevertheless
      sufficient to inhibit platelet aggregation.

PMID- 9011644
TI  - Interactions of dynorphin A and related peptides with cardiac ouabain binding
      sites.
AB  - The effect of dynorphin A (Dyn A) and related peptides on the binding of
      [3H]ouabain was examined in rat cardiac sarcolemma. Scatchard analysis of
      [3H]ouabain binding revealed the existence of two distinct sites: a high affinity
      (Kd: 20.4 nM) low capacity (Bmax: 1.55 pmol/mg protein) site and a low affinity
      (Kd: 3695 nM) high capacity (Bmax: 39.3 pmol/mg protein) site. Dyn A-(1-13) (10
      microM) interacted selectively with the low affinity [3H]ouabain binding site
      causing a significant decrease in the Bmax (from 39.3 to 22.2 pmol/mg protein)
      without altering the Kd. Dyn A-(1-13) inhibited the binding of [3H]ouabain (500
      nM) with an IC50 of 2.9 microM and a maximal inhibition of 77% of the specific
      binding activity. The non-opioid fragments Dyn A-(2-13), Dyn A-(3-13) and Dyn A
      (6-10) displayed 36%, 32% and 14% of the potency of Dyn A-(1-13) respectively;
      whereas 100 microM of Dyn A-(1-8), Leu-enkephalin (Leu-Enk) and selective ligands
      for kappa (U-50, 488H) mu [(D-Ala2-Me-Phe4.Glyol5]Enk) and delta [(D
      Ser2.Thr6]Leu-Enk) opioid receptors caused little or no inhibition of [3H]ouabain
      binding. The relative potency of various analogs and fragments of Dyn A in
      inhibiting the binding of [3H]ouabain correlated well (r = 0.89-0.90) with their
      potency in inhibiting the binding of [3H]Dyn A-(1-13) to non-opioid Dyn sites
      (Dumont and Lemaire, 1996) and to block [3H]NA uptake by cardiac synaptosomes
      (Dumont and Lemaire, 1995). In spontaneously hypertensive rats. [3H]ouabain
      binding displayed a 3.8-fold enhanced sensitivity to the action of Dyn A-(1-13)
      an effect that correlated with the enhanced ability of the peptide to inhibit
      Na+/K+-ATPase and [3H]NA uptake. The results indicate that Dyn A and related
      peptides may modulate cardiac functions through a non-opioid interaction with the
      low affinity ouabain binding site.

PMID- 9011641
TI  - Pretreatment with endothelin-1 mimics ischemic preconditioning against infarction
      in isolated rabbit heart.
AB  - We have proposed that ischemic preconditioning in rabbit hearts is initiated by
      adenosine receptor stimulation resulting in activation of protein kinase C. If
      this theory is correct then any agonist which can activate PKC should also put
      the heart into a preconditioned state. This study sought to determine whether
      endothelin-1 (ET-1), which is known to activate protein kinase C can also mimic
      ischemic preconditioning. Isolated rabbit hearts experienced 30 min of regional
      ischemia followed by 120 min of reperfusion. Infarct size was measured with
      triphenyltetrazolium chloride. In control hearts infarction was 30.3 +/- 2.5% of
      the risk zone. Preconditioning with 5 min global ischemia and 10 min reperfusion
      reduced infarct size to 5.6 +/- 0.7% (P < 0.01). Perfusion with either 10 PM ET-1
      at constant coronary artery flow for 5 min in lieu of ischemia or 50 PM ET-1 with
      10 nM nicardipine to block the former's coronary constructive effect was quite
      protective and equipotent with preconditioning. Infarction averaged 7.2 +/- 0.8%
      and 5.8 +/- 1.7% of the risk zone, respectively. This protection could be blocked
      by PD 156 707 (10 microM), a highly specific endothelin receptor antagonist.
      Chelerythrine (5 microM), a PKC inhibitor, also aborted protection (22.0 +/- 1.7%
      infarction). However, 8-(p-sulfophenyl)theophylline (100 microM), an adenosine
      receptor blocker, given during ET-1 administration did not block ET-1's
      protective effect indicating that adenosine was not involved in the effect. PD
      156707 failed to block the protection from ischemic preconditioning (12.6 +/-
      2.3% infarction) revealing that endothelin is not an important physiological
      mediator of ischemic preconditioning. We conclude that ET-1 can mimic ischemic
      preconditioning in isolated rabbit hearts as would be predicted since its
      receptors are PKC-coupled, but that endogenous endothelin contributes little to
      ischemic preconditioning.

PMID- 9011645
TI  - Ischemic preconditioning, cardioplegia or both? Differing approaches to
      myocardial and vascular protection.
AB  - We compared the anti-ischemic efficacy of cardioplegia and ischemic
      preconditioning and whether their effects are additive for both myocyte and
      vascular protection. Isolated blood-perfused rat hearts were subjected to zero
      flow global ischemia (37 degrees C) for 30 min and reperfusion for 40 min. Left
      ventricular developed pressure (LVDP) was assessed with an intraventricular
      balloon. Coronary flow and vascular reactivity (percentage change in coronary
      vascular resistance, CVR) to 5-hydroxytryptamine (5HT; 0.0215 mmol/l) and sodium
      nitroprusside (SNP; 0.0160 mmol/l) were measured. Study 1; "dose" effect of
      preconditioning in four groups (n = 6/group): (i) controls (unprotected ischemia)
      and (ii, iii and iv) 1, 2, or 3 cycles of preconditioning (3 min ischemia + 3 min
      reperfusion) prior to ischemia. LVDP recovery in controls was 31 +/- 9%;
      preconditioning by 1, 2 or 3 cycles afforded significant (P < 0.05) improvements
      (58 +/- 6%, 54 +/- 3% and 54 +/- 5%, respectively). Overall, the pre-ischemic
      change of CVR to SNP was -28 +/- 1%. The post-ischemic response in controls was 
      4 +/- 7% (P < 0.05); with 1, 2, or 3 cycles of preconditioning the values were 
      23 +/- 4%, -24 +/- 5%, and -26 +/- 3%, respectively (P < 0.05 v controls). With
      5HT the overall pre-ischemic change in CVR was -18 +/- 2%; after ischemia a
      vasoconstrictor response was seen in all groups. Study 2: the effect of
      preconditioning added to cardioplegia with four groups subjected to 35 min
      ischemia (n = 8/group): (i) controls, (ii) one cycle of preconditioning (3 min
      ischemia + 3 min reperfusion), (iii) cardioplegia with St Thomas' solution
      immediately prior to ischemia, and (iv) preconditioning followed by cardioplegia
      prior to ischemia. The recoveries of LVDP were 26 +/- 6%, 44 +/- 2%, 53 +/- 3%
      and 54 +/- 4%, respectively (P < 0.05 all interventions v controls). Post
      ischemic CVR increased greatly in controls (+ 167 +/- 60% of its pre-ischemic
      value) but was little changed in groups (ii), (iii), and (iv) (+ 11 +/- 7%, + 27
      +/- 10% and -2 +/- 6% respectively; P < 0.05 v controls). The post-ischemic
      change in CVR to SNP was protected by all interventions (-21 +/- 1%, -21 +/- 1%
      and -22 +/- 1% v -14 +/- 2% in controls; P < 0.05). Again, the post-ischemic
      response to 5HT was vasoconstriction in all groups. In conclusion,
      preconditioning and cardioplegia alone afford similar and substantial protection
      of post-ischemic contractile and vascular functions. In general, the combination
      of the two techniques afforded no significant additional protection.

PMID- 9011646
TI  - Developmental changes in the effects of pH on contraction and Ca2+ current in
      rabbit heart.
AB  - Protons inhibit Ca2+ current and contraction in heart muscle. The present study
      compares the effects of lowering the pH of the bath solution on single-cell
      contraction, action potential configuration and Ca2+ currents between neonatal
      and adult rabbit hearts. We found that a reduction of extracellular pH from 7.3
      to 6.3 decreased cell contraction amplitude to 84.3% of control in isolated
      neonatal myocytes. A comparable change in extracellular pH resulted in a decrease
      in cell contraction to 56.2% of control in adult cells. Similarly, tension
      generation in intact neonatal papillary muscles was less sensitive to a decrease
      in external pH as compared to papillary muscles from adult animals. In addition,
      acidosis caused a less pronounced inhibition of Ca2+ current in neonatal cells
      than in adult cells (85 +/- 4% nu 62 +/- 4% of control, pH = 6.3, P < 0.001; 63
      +/- 5% nu 32 +/- 5% of control, pH = 5.8, P < 0.001). Thus, the effect of
      external acidosis on myocardial contractility is commensurate with the effect on
      trans-sarcolemmal Ca2+ current. The membrane potential at which peak Ca2+ current
      occurred was not altered by low pH in neonatal cells but was shifted toward
      positive potentials by 17.7 mV in adult myocytes. Further, low external pH
      solution reduced Ca2+ current conductance more in adult cells than in neonatal
      cells. Moreover, action potential configuration in neonatal cells was altered
      less by acidosis as compared with adult cells. These findings may help explain
      the greater resistance of neonatal hearts to extracellular acidosis.

PMID- 9011648
TI  - Communications to the International Conference on Dehydration, Rehydration and
      Exercise in the Heat. Nottingham, United Kingdom, 1-5 November 1995.

PMID- 9011647
TI  - Nitric oxide mitigates leukocyte adhesion and vascular leak after myocardial
      ischemia.
AB  - Tissue edema is a facet of ischemia/reperfusion injury in many organs,
      polymorphonuclear leukocytes (PMN) presumably playing a contributory role. We
      studied the intracoronary adhesion of PMN and its effect on vascular permeability
      during reperfusion in isolated guinea-pig hearts. After a global ischemia of 15
      min duration. PMN (10(7)) were infused into the coronary system during the first
      minute of reperfusion. PMN adhesion was measured as difference of applied PMN and
      those recovered in the effluent perfusate. Coronary permeability was assessed by
      measuring the rate of transudate formation (TF) on the epicardial surface, before
      as well as 5, 15 and 30 min after ischemia. Experiments were also performed in
      the presence of the NO-synthase inhibitor nitro-L-arginine (10 microM) and the
      ACE-inhibitor ramiprilat (2 microM), the latter known to enhance endogenous
      nitric oxide formation. Furthermore, the radical scavenger uric acid (0.5 mM) was
      applied either before and during ischemia or starting after PMN application.
      Ischemia/reperfusion increased coronary PMN adherence from 23 +/- 1% (basal) to
      33 +/- 2%. Whereas ischemia alone did not influence TF (about 100 microliters/min
      during reperfusion), postischemic PMN infusion led to progressive TF. With nitro
      L-arginine, PMN adhesion rose to 45 +/- 3%; TF increased to 212 +/- 30
      microliters/min. In contrast, ramiprilat caused post-ischemic adhesion and TF to
      decline to basal values. In the presence of uric acid (UA) PMN adhesion declined
      to 26 +/- 2%, however, the subsequent increase in TF after withdrawal of UA was
      not markedly attenuated. On the other hand, infusion of UA after application of
      PMN caused a significant decrease of TF. The extracellular antioxidants
      SOD/catalase were without effect. As shown using luminol enhanced
      chemiluminescence. No was able to scavenge oxygen free radicals released by
      activated PMN. These findings indicate that enhanced PMN adhesion in reperfusion
      leads to an increase in coronary permeability. Scavenging of oxygen free radicals
      with NO or UA appears to mitigate both, postischemic PMN adhesion and PMN-induced
      vascular injury, even after adhesion.

PMID- 9011649
TI  - Fosphenytoin: a feasible alternative to phenytoin for seizure therapy.

PMID- 9011650
TI  - [Diagnosis and minor invasive methods of treatment of nonparasitic hepatic
      cysts].
AB  - 135 patients have been evaluated to improve methods of diagnosis and treatment of
      nonparasitogenic liver cysts. Ultrasound, ETA, indirect hemagglutination were
      used for differential diagnosis. Target thin-needle aspiration biopsy under the
      ultrasound control with subsequent cytologic studies was performed in all the
      patients. Most informative data have been provided by enzyme immunoassay and
      indirect hemagglutination. 118 patients have been successfully treated with
      puncturing, drainage and sclerosing of the cavity walls with 96% ethanol. There
      were no cases of recurrence, morbidity, mortality. Surgery has not been performed
      in 17 patients with small-size cysts.

PMID- 9011651
TI  - [Choice of treatment of destructive pancreatitis and its complications].
AB  - Choice of a proper method of treatment of complicated acute pancreatitis remains
      indefinite. The results of treatment of 130 patients with acute destructive
      pancreatitis complicated with pancreatic pseudocysts have been analysed. The
      authors formulate individual indications to minor surgery under the ultrasound
      control. The classical type of surgery was used only in patients with calculous
      pancreatitis complicated with pseudocysts (14). In other patients various types
      of transcutaneous ultrasound controlled procedures were used. Pilot experience of
      placing cystoduodenoanastomosis under ultrasound endoscopic control is described.
      Letal outcomes were absent. The rate of recurrence in external drainage was 10,
      5%; there were no cases of recurrence in internal drainage of pseudocysts. The
      period of long-term follow-up was 58 months.

PMID- 9011652
TI  - [The use of contact impulse-periodic YAG-ND laser in surgery of major duodenal
      papilla].
AB  - YAG-Nd impulse-periodic laser scalpel in elimination of major duodenal papilla
      stenosis was tested experimentally. The direct damaging influence of the laser
      was tested in acute experiments and the optimal power of irradiation (5 W) was
      chosen. The processes of regeneration of the wound inflicted by laser irradiation
      were tested in chronic experiments. It is shown, that regeneration was
      accompanied with minimal leucocyte infiltration and complete healing of the wound
      is achieved in 28 days.

PMID- 9011653
TI  - [The problem of acute pain in postoperative period].
AB  - The problem of postoperative pain remains actual despite the existence of a
      variety of pharmaceutical and nonpharmaceutical methods of anesthesia. Acute
      postoperative pain is an essential component of the surgical stress syndrome.
      Opioid analgetics (Buprenorfin, Nubain, Tramal, Promedol, Morphine) take the
      leading position among other types of analgetics. Present-day individual approach
      to administration of analgetics is still imperfect. The use of a standard dose of
      analgetics appears to be inadequate in a number of patients. The increase of
      opioids dose may lead to adverse reactions. In view of this it is valid to use
      nonsteroid antinflammatory medicines (Ketorolac). The choice of a proper dose of
      an analgetic is critically important in achieving adequate anesthesia. Patient
      controlled analgesia (PCA) or "analgesia on demand" is an alternative to
      administration of analgetics. The major advantage of PCA is the opportunity to
      achieve the rate of analgesia, according to individual demand of a patient.
      Besides, PCA allows to reach the desired effect much faster and to maintain the
      stable plasma level of an analgetic. 2-year experience of the PCA use in more
      than 200 patients of the National Research Centre for Surgery ICU has been
      analysed. The authors advocate use of PCA in clinical practice.

PMID- 9011654
TI  - [Aspirative lipectomy in patients with alimentary-constitutional obesity].
AB  - The results of aspirative lipectomy in patients with 2nd and 3rd stage of
      alimentary-constitutional obesity are analysed. The effectiveness of lipectomy
      with surgical creation of a small ventricle and without previous surgery, has
      been demonstrated. The criteria of patients selection, based on their somatic and
      psychic features, are formulated. Aspirative lipectomy has certain advantages
      over other types of plastic surgery as it has the minimal rate of postoperative
      complications.

PMID- 9011655
TI  - [Blood flow and free radical oxidation of lipids in gastric and duodenal mucosa
      in complicated duodenal ulcers].
AB  - 38 patients with complicated duodenal ulcer were examined with polarographic
      method. The significant decrease of tissue blood flow was revealed in all
      segments of gastroduodenal zone. The increased level of free-radical oxidation of
      lipids was determined in duodenal mucosa and ulcer edges. Disorders of blood
      supply and activation of free-radical lipid oxidation play an important role in
      the mechanism of ulcer formation. The drugs improving blood supply and
      antioxidants should be used in combined therapy and preoperative preparation.

PMID- 9011656
TI  - [Immune system defence and its correction in patients with chronic inflammatory
      disorders of lower extremities].
AB  - The factors of immune defense were studied in 83 patients. Chronic osteomyelitis
      of foot and shin was in 48 patients (hematogenic osteomyelitis in 36 patients,
      posttraumatic osteomyelitis-in 12 patients). Trophic ulcers were in 25 patients:
      in 36% in the presence of diabetes mellitus; diabetic angiopathy complicated with
      diabetic gangrene was in 10 patients. The complex of immune and morphological
      changes, developing chronic inflammation underlying chronic course of disease,
      have been detected by clinical trials. The development of immune insufficiency
      makes it necessary to use various methods of immunocorrection (pharmacological,
      biological, physical) in treatment of such patients that will decrease rate of
      postoperative morbidity and improve results of treatment.

PMID- 9011657
TI  - [Repair of the wounded and resected kidney surface by the flap of musculus
      obliques externus abdominus (experimental study)].
AB  - The experimental studies in 15 human cadavers and 15 animals (dogs) have been
      performed to test the use of the flap musculus obliques externus abdominis in
      plastic repair of wound and resected kidney surface. The vascular and nervous
      bundle of the muscle has been detected. It is easy to mobilise the muscle, that
      has good hemostatic, fixing, and plastic properties. Morphological tests of the
      flap demonstrated no signs of necrosis. There were no changes in kidney
      parenchyma either.

PMID- 9011658
TI  - [Laser surgical treatment of neurofibromas].
AB  - In the past six years 24 patients with NF I were treated by laser-surgical
      technique. By applying whole-body therapy, all neurofibromas on the skin surface
      and in the subcutis were removed. With the passage of time our method of laser
      surgical LPPL technique has become more sophisticated in order to achieve radical
      removal of all neurofibromas on the surface of the body. Our follow-up
      examinations have shown there to be no recurrence of neurofibromas eradicated by
      laser-surgical treatment provided they are removed completely and radically. In
      extreme of NF, our therapy is based in part on conventional surgical. Altogether
      the removal of all neurofibromas, including the smallest sizes, cannot be
      accomplished without laser-surgical technique. Now, the technique described
      represent the sole successful remedy of patients suffering from NF I.

PMID- 9011660
TI  - [Sipple syndrome].

PMID- 9011659
TI  - [Clinical results of Fortum and Zinacef trial in Burn Centers of Russia].

PMID- 9011661
TI  - [Advantages and disadvantages of stomach resection with PU anastomosis in
      treatment of gastric and duodenal peptic ulcers].

PMID- 9011662
TI  - [Pathogenesis and treatment of Crush syndrome in it's intermediate and late
      stages].

PMID- 9011663
TI  - [Surgical risk factors: age?].

PMID- 9011664
TI  - [Topical problems in classification and treatment of disseminated purulent
      peritonitis].
AB  - A critical analysis of modern classifications of peritonitis has been done. The
      article is based on the analyses of 347 patients with peritonitis in the phase of
      subcompensation and decompensation (polyorganic failure). The author suggests to
      differentiate peritonitis according to the character of inflammation and rate of
      dissemination: diffuse peritonitis (local, disseminated and general) and
      localized (abscesses and infiltrates). The term "general peritonitis" should not
      be used because it combines the definition of "diffuse" and "disseminated"
      peritonitis. The programmed staged peritoneal lavage (cleaning and revision of
      peritoneum) is advocated as a method of choice in the treatment of residual
      infection. Nasointestinal drainage of small intestine should be used in treatment
      of paralytic ileus.

PMID- 9011665
TI  - [The late results of the surgical treatment of congenital anomalies of the
      bronchopulmonary system in childhood].
AB  - The long-term results of operative management in a series of 98 children
      presenting congenital anomalies of the bronchopulmonary system, aged 6 months to
      17 years, are studied. Of the total, 3 children (3.1 per cent) are operated for
      pulmonary sequestration, 25 (25.5 per cent)--for bronchogenic cysts, 19 (19.3 per
      cent)--for polycystic conditions, 2 (2.0 per cent)--bronchial stenosis, 18 (18.1
      per cent)--infantile (congenital) lobar emphysema, and 30 (31 per cent)-
      bronchiectasia. Postoperative follow-up period--from 6 months to more than ten
      years. An overall assessment is done of the results on the basis of catamnestic
      data, objective status, x-ray study, functional examinations, and in isolated
      cases--CAT and bronchography. PaO2 formalization is documented within a year of
      the operation. The minute volume values depend on the number of segments
      resected, with their recovery being quicker in children with bronchogenic cysts
      polycystosis and congenital lobar emphysema, as compared to the one in
      bronchiectasia. In 87.8 per cent of children very good long-term results with a
      complete cure are obtained. The inference is reached that in children pulmonary
      resections are well tolerated, with ensuing complete functional restoration of
      the lung.

PMID- 9011666
TI  - [Traumatic lesions of the thoracic and abdominal organs in childhood].
AB  - This is a retrospective analysis of 651 children, aged 0 to 14 years, presenting
      chest and abdominal injuries, treated over a 6-year period in the section of
      pediatric surgery of the Emergency Medicine Institute "Pirogov". The results of
      studies on the etiopathogenesis of chest and abdominal trauma, patterns of
      associated lesions and quality of prehospital aid are discussed. Experience with
      the application of updated noninvasive and invasive methods of diagnosis, as well
      as the scope of surgical approach to the variety of lesions by resorting to organ
      sparing and organ salvaging operative procedures are analyzed. On the basis of
      observations and experience gained to date, the indications for application of
      the prospective method of nonoperative treatment of certain organic lesions in
      the practice of pediatric surgery are broadened. The overall research project
      provides good reason to work out an algorithm of the therapeutic approach to
      children presenting abdominal and chest trauma.

PMID- 9011668
TI  - [Analgesia in traumatism in childhood].
AB  - The current trends of pain treatment from anesthesiological viewpoint mark
      considerable progress. The ever increasing incidence of injuries in childhood
      (traffic accidents and home injuries alike), the different mechanism involved,
      and the multiple damage to organs and systems make mandatory prompt assessment of
      the condition, diagnosing and adequate therapeutic approach. Analgesia as an
      essential element of anesthesia is routinely applied to pediatric trauma cases.

PMID- 9011667
TI  - [The characteristics of changes in the hemodynamics and respiratory function of
      children with severe closed abdominal trauma].
AB  - Out of 566 children with closed abdominal trauma, treated in the EMI "Pirogov"
      over a five-year period, 79 present serious impairment of the basic vital
      functions (respiration, hemodynamics and the like) connected with the trauma and
      not infrequently with massive blood loss, necessitating the undertaking of
      resuscitation measures and intensive care. Of the latter 67 are restored to
      health, and in twelve the outcome is fatal. In terms of hemodynamic parameters a
      significant tachycardia along with maintaining normal or even increased arterial
      pressure are the most characteristic, whereas hypotension is present in 6.4 per
      cent of successfully cured children only on the first day. Regardless of the fact
      that merely 13.4 per cent of them have direct chest traumas, the gas exchange is
      considerably disturbed by hypoxemia--in 89 per cent on the first, and in 100 per
      cent of the children on the third postinjury day; in one-fourth of the cases the
      hypoxemia is markedly expressed--below 8.0 kPa (60 mm Hg). Along with the
      decrease in hemoglobin level the latter accounts for pronounced oxygen transport
      impairment. During the first postinjury day, the acid-base metabolism is
      characterized by metabolic acidosis development (in 44 per cent of children),
      with metabolic alkalosis becoming manifest during the next few days. Twelve
      children presenting severe combined injuries die within several hours of the
      accident with signs of a serious traumatic-hemorrhagic shock, or within 2-3 days
      thereafter with evidence of multiple organ failure.

PMID- 9011669
TI  - [Malignant neoplasms and intestinal obstruction in children 3 to 15 years old].
AB  - Observations on one of the rare complications in children presenting malignant
      neoplasms of the abdominal cavity and retroperitoneal space are described. Over a
      7-year period, operative treatment is undertaken in 42 children aged 3 to 15
      years. In eleven of them (26.42 per cent) it is a matter of mechanical ileus. The
      type of bowel obstruction in the series of children under study is a follows:
      obturation-in three and adhesion-in five cases. The obturation involves the large
      intestine, and is due to pressure of a neoplastic process in advanced stage of
      development on the colon. Ileus due to adhesions occurs after operative removal
      of the neoplastic formation. The essential differences in type of intestinal
      obstruction in children with malignant neoformation in the abdominal region from
      the one in adult patients justify the report on the observations.

PMID- 9011670
TI  - [The intensive treatment of children with laparoscopies after ileus peritonitis].
AB  - Experience gained with the treatment of children undergoing laparostomies,
      necessitating numerous anesthesias and operative revisions in the early post
      operative period, is shared. The open abdominal cavity is the cause of additional
      loss of liquids, requiring in turn adequate compensation with electrolyte
      solutions. Early administration of parenteral feeding contributes to prompt
      postoperative recovery. The active complex management, including antibacterial
      and immunostimulating therapy, as well as application of hyperbaric oxygenation
      in the event of severe infection, lead to a favourable outcome.

PMID- 9011671
TI  - [The diagnostic-therapeutic problems in acute suppurative destructive
      pleuropulmonary diseases in childhood].
AB  - Over a ten-year period (1985 through 1994), 183 children with acute purulent
      destructive pleuropulmonary disease undergo treatment in the pediatric chest
      surgery department of the Medical Faculty-Sofia. Their distribution by age is as
      follows: 0-1 y. -28 children (15.2 per cent), 1-3 y.-67 (36.4 per cent), and 3-15
      y. -88 (48.4 per cent). To assess the lung condition, and specify the form of
      disease and therapeutic approach, conventional and contrast roentgenography,
      thoracoscopy and CAT are performed. St. aureus is the etiological contributory
      cause in 28.9 per cent of patients, gram-negative flora-in 32.4 per cent, mixed
      microbial flora-in 33.2 per cent, and in the remainder no causing agent is
      isolated (15.5 per cent). All patients are subjected to complex treatment. In 23
      children (12.5 per cent) the pleural complication is treated by pleural puncture,
      and in 138 (75.5 per cent)-by drainage of the pleural cavity. In 22 children
      (12.0 per cent) thoracotomy is done with varying in size pulmonary resection. In
      six children (3.2 per cent) the outcome is fatal.

PMID- 9011672
TI  - [Myorelaxants in childhood].

PMID- 9011673
TI  - [Idiopathic perforation of the extrahepatic bile ducts in a nursing infant].
AB  - The report concerns a two-month-old suckling, affected on the 20th day of life
      with occurrence of icterus, dark urine and acholic stool, and on the 34th day-
      fever, vomiting and enlargement of the abdomen. Bile ascites is demonstrated by
      abdominal puncture, and perforation of the extrahepatic biliary ducts--by
      hepatobiliary scintigraphy. In the course of emergency laparotomy, diffuse bile
      peritonitis is established against the background of punctiform perforation at
      the site of d. cysticus and d. hepaticus communis union. Following sanation of
      the abdominal cavity, a draining catheter is inserted into the perforation area.
      The serious postoperative course, characterized by progressive hepatic failure,
      results in a fatal outcome on the third postoperative day. The etiopathogenesis,
      clinical symptomatology, timely diagnosis and effective operative management of
      this exceptionally rare surgical disease in children are discussed against the
      background of pertinent literature data survey.

PMID- 9011674
TI  - [Fibrous hamartoma in childhood--a report of a rare case from practice].

PMID- 9011675
TI  - [Congenital lobar emphysema in childhood].
AB  - Over a 20-year period, thirty-two children with infantile (congenital) lobar
      emphysema (ILE) are subjected to treatment in the department of pediatric chest
      surgery--Emergency Medicine Institute "N. I. Pirogov". The age distribution of
      the patients is as follows: neonates--7 (21.8 per cent), sucklings--17 (53.8 per
      cent), 1 y.--5 (15.6 per cent), 2 y.--2 (6.2 per cent), 12 y.--1 (3.1 per cent).
      In seventeen children (53.3 per cent) the lobar emphysema is located in the left
      upper lobe. The onset of the clinical picture is in the neonatal period (17
      cases, 53.3 per cent) and in the suckling age (13 cases, 40.6 per cent), and
      becomes manifest with: dyspnea--16 children (50.0 per cent), tachypnea--26 (81.2
      per cent) and cyanosis--18 (56.2 per cent). Twenty-seven children are admitted
      with varying degree respiratory insufficiency (84.4 per cent). Diagnosis is made
      on the ground of conventional roentgen examinations mainly. Stenosis of the
      respective lobar bronchus is discovered in 8 children by CAT and bronchoscopy.
      Scarce vascular pattern is established angiopulmographically in 87.5 per cent of
      children, and fan-like displacement of the vessels-in 75.0 per cent. All children
      undergo operation--removal of the emphysematous lobe. Morphological study of the
      resected lung shows cartilage deficit in the bronchial wall in 14 children (34.5
      per cent), bronchial stenosis in 26.2 per cent whereas in 43.8 per cent the
      underlying cause of ILE is unclear. In 4 children (12.5 per cent) the outcome is
      lethal because of inflammatory pulmonary process in the postoperative period.

PMID- 9011676
TI  - Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung.
AB  - Human thioredoxin is a polypeptide with thiol groups, possessing reducing
      activity, which is proved to have the ability to reduce active oxygens. This
      study evaluated the effect of human thioredoxin on the ischemia-reperfusion lung
      injury and the roles of human thioredoxin on active oxygens by chemiluminescence
      examination. The left hilum of the lung of Japanese white rabbits was occluded
      for 110 minutes and then reperfused for 90 minutes. Ten, 30, 60, and 90 minutes
      after reperfusion the right hilum was occluded for 5 minutes and the pulmonary
      functions of the left lung were examined. The animals were divided into four
      groups, three ischemia groups and a sham group (without occlusion; n = 6). The
      ischemia groups received human thioredoxin, 60 mg/kg (n = 10), N-acetylcysteine,
      150 mg/kg (n = 7), or saline solution (control, n = 10) during reperfusion. Three
      rabbits in the human thioredoxin group and the control group were used to measure
      active oxygens with a cypridina luciferin analog. An additional group of
      reperfused lungs (n = 3) that were given superoxide dismutase after 110 minutes
      of ischemia was established to identify chemiluminescence examination. Compared
      with the sham group, reperfusion after 110 minutes of ischemia produced a
      significant lung injury in the control group. Among the ischemia groups, the
      human thioredoxin group showed significantly higher arterial oxygen tension at
      30, 60, and 90 minutes after reperfusion than the control group, although there
      was no significant difference between the N-acetylcysteine and control groups.
      Histologically, intraalveolar exudation, interstitial thickening, and cellular
      infiltration were seen in the control group, whereas in the thioredoxin group
      alveolar structure was well preserved. In the measurement of active oxygens the
      chemiluminescence in the human thioredoxin group was less than that in the
      control group and as little as that in the group administered superoxide
      dismutase. We concluded human thioredoxin attenuated ischemia-reperfusion injury
      by involving active oxygens in rabbit lungs.

PMID- 9011677
TI  - Transplantation of genetically marked cardiac muscle cells.
AB  - We examined the possibility that cardiomyocytes could be genetically marked or
      modified before being grafted to the heart under conditions applicable to the
      clinical setting. We used a replication-defective recombinant adenovirus carrying
      the beta-galactosidase reporter gene, and delivered it to cultured murine fetal
      cardiac myocytes. Virtually all fetal cardiomyocytes in a primary culture
      expressed beta-galactosidase 24 hours after recombinant adenovirus infection.
      These cells were transplanted to the hearts of syngenic adult recipient mice.
      Expression of the beta-galactosidase gene in the grafted cells was demonstrated
      by staining with 5-bromo-4-chloro-3-indoyl-beta-D-galactosidase, resulting in a
      blue color at the histochemical level and an electron-dense deposit on
      transmission electron microscopic analysis. Gene expression was recognized from 7
      days to 12 weeks after transplantation. Implanted cardiomyocytes aligned
      themselves along the layers of the host myocardium. Formation of gap junctions
      was demonstrated by transmission electron microscopy. Neither inflammation nor
      fibrous scar tissue was detectable by histologic analysis. This study
      demonstrates that ex vivo gene transfer to the heart by means of the adenoviral
      vector is possible.

PMID- 9011678
TI  - Procollagen production in fresh and cryopreserved aortic valve grafts.
AB  - Long-term durability of aortic valve allografts may be enhanced by cellular
      capacities for regeneration and repair. To evaluate aortic valve graft production
      of an important structural protein, rat aortic roots were implanted
      heterotopically into the abdominal aorta of recipient rats. Grafts were either
      syngeneic or strongly allogeneic, were implanted either fresh or after
      cryopreservation, and were left in place 2 to 21 days after implantation. A total
      of 80 aortic valve grafts and the corresponding native aortic valves were
      examined. The grafts were retrieved and immunocytochemically stained for the
      presence of procollagen, a precursor to collagen. Regardless of
      histocompatibility or preservation, grafts exhibited consistent procollagen
      presence that equaled or exceeded that seen in the corresponding native valves.
      Positive procollagen staining was predominantly in the aortic wall. The most
      prominent staining was near the hinge point of the valve leaflets, with no
      staining in the free portion of the leaflets. Staining with alpha-actin
      demonstrated vascular smooth muscle in sites remote from the areas positive for
      procollagen, which suggests that vascular smooth muscle was not responsible for
      the procollagen production. These findings indicate that cryopreservation is
      compatible with persistent fibroblast viability and in vivo protein synthesis by
      both syngeneic and allogeneic aortic valve grafts.

PMID- 9011679
TI  - Direct vasodilator effect of milrinone, an inotropic drug, on arterial coronary
      bypass grafts. FANZCA .
AB  - Milrinone is an inotropic drug with vasodilator activity that has been shown to
      be useful in increasing cardiac output and decreasing wedge pressure. Despite
      these advantages, it is unknown whether this drug can be used for the treatment
      of perioperative spasm of coronary bypass grafts. This study was undertaken to
      investigate the in vitro vascular effect of milrinone on internal thoracic
      arteries obtained from patients undergoing coronary artery bypass grafting. The
      results showed that milrinone produced a potent, concentration-dependent,
      preventive effect on the norepinephrine-induced contraction of internal thoracic
      arteries, as well as reversing contraction of internal thoracic arteries by
      receptor-dependent agents, including the thromboxane A2 mimetic U46619, the
      vasoconstrictor peptide endothelin-1, and the alpha1-adrenal receptor agonist
      phenylephrine. The relaxing effect of milrinone was weaker, however, on internal
      thoracic arteries contracted with 25 mmol/L potassium chloride. Comparison of
      milrinone with other vasodilators, including papaverine, nitroprusside, and
      glyceryl trinitrate, showed milrinone to be more potent than papaverine but less
      potent than nitroprusside and glyceryl trinitrate. The inhibitory effect of
      milrinone on internal thoracic artery contraction appeared as a reduction in
      contractile force, not as an increase in the values of concentrations of the
      agonists causing 50% maximal contraction, which indicates that milrinone exerts
      its vasodilator effect directly on the smooth muscles, not on the membrane
      receptors. The results also showed no significant difference in relaxing effect
      between internal thoracic artery rings with and without endothelium. In
      conclusion, this study provides experimental evidence that milrinone is a potent,
      endothelium-independent, direct vasodilator of the human internal thoracic artery
      and provides the scientific rationale for a future clinical trial with this drug
      for the perioperative treatment of internal thoracic artery spasm in cardiac
      surgical patients.

PMID- 9011680
TI  - Effect of altered blood flow on the caliber and morphology of the internal
      thoracic artery in the dog.
AB  - OBJECTIVE: The purpose of this study was to evaluate in dogs the effect of blood
      flow alteration on caliber and morphology of in situ internal thoracic arteries.
      METHODS: Six dogs underwent creation of a unilateral distal arteriovenous fistula
      between the internal thoracic artery and vein at the sixth rib to create high
      flow, and in six others the internal thoracic artery was unilaterally
      skeletonized and dissected. For both groups the contralateral internal thoracic
      artery served as the control; sides were alternated among cases. Blood flow was
      measured for shear stress calculation before and after surgical alteration. After
      2 months, internal thoracic arteries were harvested with the entire anterior
      chest plate, which was dynamically inflated and fixed with 10% formalin at a
      controlled pressure of 120 mm Hg after angiography had been done at the same
      pressure. The luminal diameters were then measured at eight levels on the
      angiograms. Arterial tissue samples were taken at three levels and embedded,
      sectioned, and treated with hematoxylin-eosin and Verhoeff-van Gieson stains.
      Digital imaging analysis was used for quantitative morphometric studies. RESULTS:
      All fistulas remained patent. In comparison with control arteries, high-flow
      internal thoracic arteries dilated and low-flow internal thoracic arteries
      narrowed, which was associated with significant change in shear stress for both
      groups. There were no substantial structural changes in the walls of either
      group. CONCLUSION: In the dog, the luminal diameter of the internal thoracic
      artery responds to altered blood flow without intimal thickening or other
      undesirable wall changes.

PMID- 9011681
TI  - The treatment of patients with infected implantable cardioverter-defibrillator
      systems.
AB  - OBJECTIVE: The purpose of this study was to evaluate the treatment of patients
      with infected implantable cardioverter-defibrillator systems. METHODS:
      Retrospective analysis was done of the cases of 21 patients treated for
      implantable cardioverter-defibrillator infection during an 11-year period.
      RESULTS: Of 723 cardioverter-defibrillator implantations (550 primary implants,
      173 replacements), nine (1.2%) were complicated by early postoperative device
      related infections. Late infections developed in two patients 19 and 22 months,
      respectively, after implantation. Ten other patients were transferred to our
      institution for treatment of cardioverter-defibrillator infection. The time from
      implantation to overt infection was 2.2 +/- 1.3 months, excluding the two late
      infections. The responsible organisms were Staphylococcus aureus (9),
      Staphylococcus epidermidis (6), Streptococcus hemolyticus (1), gram-negative
      bacteria (3), Candida albicans (1), and Corynebacterium (1). All patients were
      treated with intravenous antibiotic drugs. Total system removal was done in 15
      patients and partial removal in 2; in 4, the cardioverter-defibrillator system
      was not explanted. There were no perioperative deaths. A new implantable
      cardioverter-defibrillator system was reimplanted in 7 patients after 2 to 6
      weeks of antibiotic therapy. Ten patients were treated without reimplantation (2
      arrhythmia operation, 8 antiarrhythmic drugs). Four patients (3 patients without
      explantation and 1 with partial system removal) were treated with maintenance
      long-term antibiotic therapy. During a mean follow-up of 21 +/- 2.8 months, no
      patient had clinical recurrence of infection. One patient treated with
      antiarrhythmic drugs without system reimplantation died suddenly. CONCLUSIONS:
      Infections that involve implantable cardioverter-defibrillator systems can be
      safely managed by removing the entire system with reimplantation after
      intravenous antibiotic therapy. In selected patients in whom the risk for system
      explantation is high and anticipated life expectancy is short, long-term
      antibiotic therapy to suppress low-virulence infections may represent an
      acceptable alternative.

PMID- 9011682
TI  - Routine chest roentgenography on admission to intensive care unit after heart
      operations: is it of any value?
AB  - The need for routine immediate postoperative chest roentgenography after heart
      operations has recently been questioned. In this study we investigated the impact
      of routine postoperative chest roentgenography on treatment instituted in the
      cardiovascular intensive care unit immediately after heart operations done via
      median sternotomy. A total of 404 random patients admitted to the cardiovascular
      intensive care unit underwent clinical (positioning of endotracheal tube,
      nasogastric tube, and pulmonary artery catheter) and laboratory (oxygenation)
      assessment by a cardiovascular intensive care unit physician according to a
      strict protocol. After clinical assessment, chest roentgenography was done for
      all admitted patients and the findings reviewed by the same physician. Pathologic
      conditions noted were recorded on the study form together with any required
      treatment. Eighteen patients (4.5%) out of 404 required intervention because of
      abnormalities detected by the chest x-ray film but not predicted by the initial
      physical and laboratory assessment. None of the pathologic conditions detected
      was life threatening. We conclude that chest roentgenography done on admission to
      the cardiovascular intensive care unit should be done only if clinical and
      laboratory assessment indicate the possibility of underlying pathologic
      conditions that can only be confirmed or diagnosed by chest roentgenography.

PMID- 9011683
TI  - St. Jude Medical valve prosthesis: an analysis of long-term outcome and
      prognostic factors.
AB  - Between 1979 and 1984, 321 patients received 354 St. Jude Medical prostheses (194
      aortic, 94 mitral, 1 tricuspid, and 32 multiple valve replacements). Follow-up
      was 96% complete (2967 patient-years; mean 9.5 years per patient). Actuarial
      event-free rates at 10 years and linearized rates (in parentheses) of late
      complications were as follows: embolism, 85.0% +/- 2.3% (2.3% per patient-year);
      anticoagulant-related hemorrhage, 74.8% +/- 2.7% (3.3% per patient-year);
      cerebrovascular accident, 81.8% +/- 2.5% (2.6% per patient-year); prosthesis
      thrombosis, 98.5% +/- 0.7% (0.1% per patient-year); endocarditis, 97.2% +/- 1.1%
      (0.4% per patient-year); prosthesis dysfunction, 97.1% +/- 1.0% (0.4% per patient
      year); hemolytic anemia, 98.5% +/- 0.7% (0.1% per patient-year); reoperation,
      97.4% +/- 1.0% (0.4% per patient-year); overall mortality, 63.3% +/- 2.7% (4.2%
      per patient-year); and valve-related death (including sudden death), 84.7% +/-
      2.2% (1.4% per patient-year). Independent preoperative risk factors were as
      follows: (1) for embolism, cardiac failure as indication for operation and
      history of prior systemic embolism; (2) for cerebrovascular accidents, the same
      two factors and age; (3) for endocarditis, diabetes, chronic alcoholism, and
      aortic valve replacement; (4) for overall mortality, age, ejection fraction (or
      cardiac index or cardiothoracic index), chronic alcoholism, and history of
      systemic embolism; and (5) for valve-related death, chronic alcoholism,
      degenerative cause of valve disease, and prosthetic diameter 23 mm or smaller.
      Ninety percent of survivors were in New York Heart Association functional class I
      or II at the end of follow-up. In conclusion, this study confirms the excellent
      durability of the St. Jude Medical valve and the remarkable functional benefit
      for the majority of the patients. However, prosthesis-related complications are
      still common, particularly for small-diameter prostheses. Outcome is strongly
      related to the patient's preoperative cardiac condition and to the adequacy of
      anticoagulation control.

PMID- 9011684
TI  - Left ventricular adaptation to aortic regurgitation in conscious dogs.
AB  - OBJECTIVE: Cardiac failure as a result of valvular heart disease remains a major
      clinical problem that frequently leads to ventricular dysfunction, myocardial
      failure, and even death. The development of irreversible myocardial damage may be
      especially insidious in volume overload as a result of aortic or mitral
      regurgitation. METHODS AND RESULTS: Left ventricular wall volume, ventricular
      function, and myocardial performance were assessed in 10 chronically instrumented
      conscious dogs before and after creation of aortic regurgitation. Left
      ventricular wall volume was measured by serial echocardiography. Left ventricular
      function was assessed by total cardiac output, stroke work, the slope of the
      Frank-Starling relationship, and the slope of the end-systolic pressure-volume
      relationship. Myocardial performance was assessed by the slope of the myocardial
      power output versus end-diastolic strain relationship. End-diastolic wall stress
      and volume both increased acutely and remained elevated after creation of aortic
      regurgitation. Peak systolic wall stress increased initially (1 to 3 weeks) from
      336 +/- 30 to 369 +/- 55 mm Hg but returned to control values as left ventricular
      wall volume increased from 78 +/- 13 to 88 +/- 16 ml after development of
      compensatory hypertrophy. Left ventricular systolic function remained constant or
      increased and was maintained initially by increased myocardial performance, which
      returned to baseline levels after the development of compensatory hypertrophy.
      CONCLUSIONS: Myocardial performance and ventricular function vary independently
      in aortic regurgitation. Measures of myocardial performance such as the
      myocardial power output versus end-diastolic strain relationship may be useful in
      clinical assessment of aortic regurgitation.

PMID- 9011685
TI  - Selective motor neuron death and heat shock protein induction after spinal cord
      ischemia in rabbits.
AB  - Paraplegia is a serious complication that sometimes results from operation on the
      thoracic aorta. The mechanism of spinal cord injury has been thought to involve
      tissue ischemia, and spinal motor neurons are suggested to be vulnerable to
      ischemia. The exact mechanism, however, is not fully understood. To evaluate the
      mechanism of such vulnerability of motor neurons, we attempted to make a
      reproducible model for spinal cord ischemia and statistically analyzed cell
      damage. With this model, induction of heat shock protein 70 (HSP70) and heat
      shock cognate protein (HSC70) messenger ribonucleic acid molecules were
      investigated with Northern blot analysis for up to 7 days of reperfusion after 5
      or 15 minutes of ischemia. Immunohistochemical studies of their proteins were
      also done. (heat shock proteins are a set of markers of neuronal injury after
      ischemia.) After 5 minutes of ischemia, there was no induction of HSP70 and HSC70
      messenger ribonucleic acid molecules or their proteins, and all cells remained
      intact. In contrast, after 15 minutes of ischemia, HSP70 messenger ribonucleic
      acid was induced at 8 hours of reperfusion, and HSC70 messenger ribonucleic acid
      was expressed continuously at the control level. Immunoreactivity of HSP70
      protein was slightly induced at 8 hours of reperfusion selectively in motor
      neurons, and about 70% of motor neuron cells showed selective cell death after 7
      days of reperfusion. This study demonstrated induction of HSP70 messenger
      ribonucleic acid and its protein in motor neuron cells after transient ischemia
      in the spinal cord. This phenomenon was not accompanied by HSC70 induction.

PMID- 9011686
TI  - Effects of cryopreservation on contractile properties of porcine isolated aortic
      valve leaflets and aortic wall.
AB  - Human semilunar donor heart valves can be stored in banks, awaiting
      transplantation. To evaluate the result of the preservation protocols, a
      quantitative description of the tissue is necessary. In this study we
      investigated in a quantitative way the contractile properties of fresh and
      cryopreserved porcine isolated aortic heart valve leaflets in response to a
      number of endogenous vasoactive compounds. The responses of strips of the aortic
      wall were included for comparison. Contraction was measured isometrically in
      response to potassium (K+; 100 mmol/L), 5-hydroxytryptamine (1 nmol/L to 100
      micromol/L), noradrenaline (1 nmol/L to 100 micromol/L), endothelin-1 (0.01
      nmol/L to 0.3 micromol/L), and prostaglandin F(2alpha) (0.1 nmol/L to 10
      micromol/L). The pharmacologic parameters E(MAX) (the maximal response expressed
      as a percentage of contraction to a 100 mmol/L dose of K+) and EC50 (the
      concentration that produces 50% of the maximal effect) were calculated for every
      compound (n = 6 to 7 each). We observed that all specimens contracted in response
      to potassium. Its magnitude in fresh leaflets equaled 1.6 +/- 0.14 mN compared
      with 26.6 +/- 2.6 mN in fresh aortic wall. Noradrenaline, endothelin-1, and
      prostaglandin F(2alpha) all caused contraction in valvular leaflets and aortic
      wall, whereas 5-hydroxytryptamine caused contraction in the valvular leaflets but
      relaxation in aortic wall. After cryopreservation, the response to K+ amounted to
      24% of the response of the fresh specimens in valvular leaflets (n = 25) and 14%
      in aortic wall (n = 26). The values of E(MAX) and EC50 of the responses to
      noradrenaline, endothelin-1, and prostaglandin F(2alpha) remained unchanged.
      Although the physiologic relevance of contraction of valvular leaflets needs
      further study, its measurement may provide an additional model to verify the
      consequences of alternative methods of preservation.

PMID- 9011687
TI  - A comparison of the early and midterm results after dynamic cardiomyoplasty in
      patients with ischemic or idiopathic cardiomyopathy.
AB  - OBJECTIVE: The main goal of this study is to determine the efficiency of the
      cardiomyoplasty procedure on patients with cardiomyopathy of different origins
      (ischemic and idiopathic origins). METHOD: Between June 1993 and August 1995, 24
      patients underwent dynamic cardiomyoplasty with the left latissimus dorsi muscle
      in our institution. Early and midterm results, as well as the changes in
      hemodynamics and functional status during follow-up, were compared. RESULTS:
      Early mortality rate was 20.8% (five patients). Concomitant coronary
      revascularization, a preoperative left ventricular ejection fraction below 20%,
      and a functional capacity of class IV (intermittently) were associated with early
      mortality. The mean follow-up time was 17.3 months. Survival analysis (including
      early mortality) extending to the twenty-fourth month revealed no difference
      between the ischemic and idiopathic groups (55% vs 85%, respectively, p = 0.09).
      Functional status improved in the both groups. Ejection fractions were improved
      after cardiomyoplasty in all patients, regardless of their cause. Cardiac indices
      were higher 6 months after the operation. Changes in pulmonary capillary wedge
      pressure, peak pulmonary artery pressure, and left ventricular end-diastolic
      volume were not significant. CONCLUSION: Although cardiomyoplasty improves
      functional capacity and hemodynamics in patients with both idiopathic and
      ischemic cardiomyopathy, the idiopathic group is thought to achieve optimal
      benefit with regard to lower complication rates and lower early mortality
      expectancy owing to the absence of concomitant coronary revascularization.

PMID- 9011689
TI  - Proliferation of smooth muscle cells in acute allograft vascular rejection.
AB  - OBJECTIVES: To determine whether immune injury during acute cardiac rejection
      induces phenotypic modulation of arterial smooth muscle cells and lesion
      formation, we studied the expression of embryonic myosin heavy-chain isoform and
      degrees of intimal proliferation in aortas and coronary arteries of allografted
      rabbit hearts. Modulation of phenotype in arterial smooth muscle cells during
      acute vascular injury is a widely reported phenomenon, and proliferation and
      migration of medial smooth muscle cells contribute to development of intimal
      hyperplasia of arteries in response to immune injury. METHODS: Rabbit hearts were
      heterotopically transplanted to the neck without immunosuppression. Hearts were
      harvested at 2, 5, 7, and 10 days after transplantation. Proliferation of smooth
      muscle cells was assessed by bromodeoxyuridine labeling. Staining for
      immunohistochemical indicators was done with use of monoclonal antibodies that
      recognize T lymphocytes and all types of smooth muscle cells (SM1), adult type of
      smooth muscle cells (SM2), and embryonic myosin heavy-chain isoform. Intimal
      thickening and luminal narrowing were assessed with a computer-assisted video
      image analysis system. RESULTS: Intimal thickening and luminal narrowing in
      aortas and coronary arteries gradually increased in a time-dependent manner. The
      neointima thus formed consisted of proliferating smooth muscle cells positive for
      both SM1 and embryonic myosin heavy-chain isoform and massive T lymphocyte
      accumulation. Intimal proliferation was more prominent in aortas and large
      epicardial coronary arteries than in the intramyocardial small coronary arteries.
      CONCLUSIONS: These findings suggest that allogeneic immune injury facilitates
      phenotypic modulation of smooth muscle cells, which may contribute to subsequent
      transplantation-associated atherosclerosis.

PMID- 9011688
TI  - Tirofiban provides "platelet anesthesia" during cardiopulmonary bypass in
      baboons.
AB  - OBJECTIVE: Tirofiban (Aggrastat) is a reversible, nonpeptide inhibitor of
      platelet glycoprotein II/IIIa receptors. We tested the hypothesis that tirofiban
      preserves platelet number and function and shortens postoperative bleeding times
      in baboons after cardiopulmonary bypass. METHODS: Four groups were studied:
      control, n = 12; low-dose tirofiban (0.1 microg/kg per minute), n = 7; high-dose
      tirofiban (0.3 microg/kg per minute), n = 7; and bolus tirofiban (15 microg/kg)
      followed by 0.1 microg/kg per minute during cardiopulmonary bypass, n = 7. After
      heparin, animals were perfused for 60 minutes at 50 ml/kg per minute and 37
      degrees C with a bubble oxygenator, roller pump, and peripheral cannulation.
      Hemodynamics, platelet count, platelet aggregation to adenosine diphosphate, and
      release of beta-thromboglobulin were measured before tirofiban infusion, before
      heparin, after heparin before bypass, after 5 and 55 minutes of bypass, after
      protamine, and 60 minutes after protamine. Template bleeding times were measured
      at the same times except during cardiopulmonary bypass and 120 and 180 minutes
      after protamine administration. Platelet glycoprotein IIIa antigen was measured
      in Triton X-100 washes (Sigma Chemical Company) of the perfusion circuit after
      bypass. RESULTS: High-dose tirofiban completely prevents platelet loss during
      cardiopulmonary bypass. beta-Thromboglobulin release and sensitivity to adenosine
      diphosphate are significantly less than control at the end of bypass in all
      tirofiban groups. Template bleeding times return to preoperative values in both
      the low- and high-dose tirofiban groups 180 minutes after protamine
      administration and are significantly less than control bleeding times at both 120
      and 180 minutes after protamine. Surface glycoprotein IIIa antigen does not
      significantly differ between groups. CONCLUSION: High-dose tirofiban completely
      preserves platelet number and improves platelet function during cardiopulmonary
      bypass in baboons and significantly accelerates restoration of normal template
      bleeding times after bypass.

PMID- 9011690
TI  - Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty
      eight reexposures to aprotinin in heart operations.
AB  - The efficacy of aprotinin to reduce intraoperative bleeding tendency in cardiac
      operations has been demonstrated in several studies. Aprotinin is a polybasic
      polypeptide and has antigenic properties. Anaphylactic reactions to aprotinin
      have been described. The aim of the present study was to evaluate the prevalence
      of adverse reactions to reexposure to high-dose aprotinin. The clinical outcome
      of all patients undergoing heart operations in our institution between 1988 and
      1995 with at least two exposures to aprotinin was investigated. There were 248
      reexposures to aprotinin in 240 patients: 101 adult and 147 pediatric cases. The
      total aprotinin doses were 4.9 x 10(6) (interquartile range 2 x 10(6)) KIU
      (adults) and 1.3 x 10(6) (interquartile range 1.2 x 10(6)) KIU (pediatric
      patients). The time between the first and second aprotinin exposures was 344
      (interquartile range 1039) days. Seven adverse reactions to aprotinin were found
      (2.8%). The severity of the reaction ranged from mild (no intervention) to severe
      (longer-lasting circulatory depression despite vasopressor therapy). All patients
      survived the event. Patients with an interval less than 6 months since the
      previous exposure had a statistically higher incidence of adverse reactions than
      patients with a longer interval (5/111 or 4.5% vs 2/137 or 1.5%, p < 0.05). Two
      patients reacted to a test dose of 10,000 KIU aprotinin. Pretreatment with
      antihistaminics was done in 60% of the patients. We recommend the following
      procedure for reexposure with high-dose aprotinin: (1) delay of the first bolus
      injection of aprotinin until the surgeon is ready to begin cardiopulmonary
      bypass, (2) test dose of 10,000 KIU aprotinin in all patients with aprotinin
      treatment, (3) H1/H2 blockade in known or possible reexposures, and (4) avoidance
      of reexposure within the first 6 months after the previous exposure to aprotinin.
      With these precautions a reexposure to aprotinin in patients with a high risk of
      bleeding is justified, because the benefits of aprotinin treatment outweigh the
      relative risk of a serious allergic reaction.

PMID- 9011691
TI  - Preoperative and postoperative comparison of patients with univentricular and
      biventricular support with the thoratec ventricular assist device as a bridge to
      cardiac transplantation.
AB  - OBJECTIVES: The goal of this study was to determine whether there are differences
      in populations of patients with heart failure who require univentricular or
      biventricular circulatory support. METHODS: Two hundred thirteen patients who
      were in imminent risk of dying before donor heart procurement and who received
      Thoratec left (LVAD) and right (RVAD) ventricular assist devices at 35 hospitals
      were divided into three groups: group 1 (n = 74), patients adequately supported
      with isolated LVADs; group 2 (n = 37), patients initially receiving an LVAD and
      later requiring an RVAD; and group 3 (n = 102), patients who received
      biventricular assistance (BiVAD) from the beginning. RESULTS: There were no
      significant differences in any preoperative factors between the two BiVAD groups.
      In the combined BiVAD groups, pre-VAD cardiac index (BiVAD, 1.4 +/- 0.6 L/min per
      square meter, vs LVAD, 1.6 +/- 0.6 L/min per square meter) and pulmonary
      capillary wedge pressure (BiVAD, 27 +/- 8 mm Hg, vs LVAD, 30 +/- 8 mm Hg) were
      significantly lower than those in the LVAD group, and pre-VAD creatinine levels
      were significantly higher (BiVAD, 1.9 +/- 1.1 mg/dl, vs LVAD, 1.4 +/- 0.6 mg/dl).
      In addition, greater proportions of patients in the BiVAD groups required
      mechanical ventilation before VAD placement (60% vs 35%) and were implanted under
      emergency conditions than in the LVAD group (22% vs 9%). The survival of patients
      through heart transplantation was significantly better in patients who had an
      LVAD (74%) than in those who had BiVADs (58%). However, there were no significant
      differences in posttransplantation survival through hospital discharge (LVAD,
      89%; BiVAD, 81%). CONCLUSION: Patients who received LVADs were less severely ill
      before the operation and consequently were more likely to survive after the
      operation. As the severity of illness increases, patients are more likely to
      require biventricular support.

PMID- 9011692
TI  - Inferior mesenteric artery as a free arterial conduit for myocardial
      revascularization.

PMID- 9011693
TI  - Contribution of hyperoxia to lipid peroxidation in coronary artery operations:
      should we keep a low oxygen tension?

PMID- 9011695
TI  - Cerebral embolization is reduced with use of the stab technique for aortic
      cannulation compared with the side-clamp technique.

PMID- 9011694
TI  - Recovery of atrial function after combined treatment with surgical repair for
      organic heart disease and maze procedure for atrial fibrillation.

PMID- 9011696
TI  - Orthotopic heart transplantation for Kawasaki disease after rupture of a giant
      coronary artery aneurysm.

PMID- 9011697
TI  - Obstruction of the right pulmonary veins after the modified Fontan operation.

PMID- 9011698
TI  - Low cardiac output syndrome complicating subxiphoid pericardiostomy for
      pericardial effusion.

PMID- 9011699
TI  - Optimal dose of basic fibroblast growth factor for long-segment orthotopic
      tracheal autografts.
AB  - When a primary anastomosis of the trachea is not feasible, extensive grafting is
      required. However, despite the use of omental wrapping for revascularization,
      long-segment tracheal grafts frequently do not maintain structural integrity
      because of insufficient blood supply. We examined the use of basic fibroblast
      growth factor for preservation of long-segment tracheal autografts after
      orthotopic transplantation with omental wrapping in 23 dogs. All animals received
      orthotopic tracheal transplantation, with 14-ring autografts that occupied a
      major part of the thoracic trachea, and omental wrapping. The 23 animals were
      classified randomly into six groups as follows: no treatment (group I, n = 3),
      topical administration of fibrin glue alone (group II, n = 4), fibrin glue
      enriched with 1 microg/cm2 basic fibroblast growth factor (group III, n = 4),
      fibrin glue enriched with 5 microg/cm2 basic fibroblast growth factor (group IV,
      n = 4), and fibrin glue enriched with 10 microg/cm2 basic fibroblast growth
      factor (groups V and VI, each n = 4). The omentum that was used to wrap the
      autografts was fed by the right gastroepiploic artery in groups I to V and by
      both the right gastroepiploic artery and splenic artery in group VI. All
      autografts in groups I and II showed dissolution. Ten of 12 autografts in groups
      III, V, and VI did not maintain long-term structural integrity. By contrast, all
      autografts in group IV showed long-term viability, as demonstrated by graft
      patency, epithelialization, cartilage morphology, and vascularity. We conclude
      that treatment with fibrin glue enriched with 5 microg/cm2 basic fibroblast
      growth factor in combination with omental wrapping may prolong the viability of
      long-segment tracheal autografts.

PMID- 9011700
TI  - Long-term results of lung metastasectomy: prognostic analyses based on 5206
      cases.
AB  - OBJECTIVES: The International Registry of Lung Metastases was established in 1991
      to assess the long-term results of pulmonary metastasectomy. METHODS: The
      Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of
      thoracic surgery in Europe (n = 13), the United States (n = 4) and Canada (n =
      1). Of these patients, 4572 (88%) underwent complete surgical resection. The
      primary tumor was epithelial in 2260 cases, sarcoma in 2173, germ cell in 363,
      and melanoma in 328. The disease-free interval was 0 to 11 months in 2199 cases,
      12 to 35 months in 1857, and more than 36 months in 1620. Single metastases
      accounted for 2383 cases and multiple lesions for 2726. Mean follow-up was 46
      months. Analysis was performed by Kaplan-Meier estimates of survival, relative
      risks of death, and multivariate Cox model. RESULTS: The actuarial survival after
      complete metastasectomy was 36% at 5 years, 26% at 10 years, and 22% at 15 years
      (median 35 months); the corresponding values for incomplete resection were 13% at
      5 years and 7% at 10 years (median 15 months). Among complete resections, the 5
      year survival was 33% for patients with a disease-free interval of 0 to 11 months
      and 45% for those with a disease-free interval of more than 36 months; 43% for
      single lesions and 27% for four or more lesions. Multivariate analysis showed a
      better prognosis for patients with germ cell tumors, disease-free intervals of 36
      months or more, and single metastases. CONCLUSIONS: These results confirm that
      lung metastasectomy is a safe and potentially curative procedure. Resectability,
      disease-free interval, and number of metastases enabled us to design a simple
      system of classification valid for different tumor types.

PMID- 9011701
TI  - Thoracoscopic loop ligation of parenchymal blebs and bullae: is it effective and
      safe?
AB  - Surgeons who have gained experience and confidence with video-assisted thoracic
      surgery are now routinely applying the minimally invasive approach to treat
      patients with spontaneous pneumothorax. Although the endoscopic stapling device
      may be a preferred method for resection of parenchymal blebs or bullae, the
      stapling device is not inexpensive. In an effort to contain costs since we
      started performing the video-assisted thoracoscopic procedure in chest surgical
      diseases, we have used a self-made endoscopic loop as an alternative method. It
      has assisted us in performing bulla ablation in a cost-effective manner. Over a 4
      year period (1992 to 1996), we assessed the efficacy of ligating parenchymal
      blebs and bullae with a self-made endoscopic loop by video-assisted techniques. A
      total of 263 ligations were performed in 250 patients. Surgical indications
      included recurrence (n = 146), bilaterality of the disease (n = 13),
      hemopneumothorax (n = 7), radiologically demonstrated large bulla (n = 9),
      persistent air leak (n = 52), and nonexpansion of the lung (n = 23). There were
      no operative deaths. Early postoperative complications included a dislodged
      endoscopic loop necessitating reexploration in one patient and postoperative
      minor wound infections in 13. The average postoperative hospitalization was 4.5
      days. Two hundred seventeen patients (86.8% of all patients) were followed up for
      a median of 28 months (1 to 46 months) after the operation. There have been no
      recurrences to date. Our results showed that thoracoscopic loop ligation is safe
      and effective in managing blebs and parenchymal bullae, with a lower cost, fewer
      complications, and a lower recurrence rate than provided by standard surgical
      techniques. On the basis of our results, we advocate the use of the self-made
      endoscopic loop for ligation of parenchymal blebs and bulla in patients with
      spontaneous pneumothorax to achieve a truly cost-effective and minimally invasive
      thoracoscopic procedure.

PMID- 9011702
TI  - Recurrence of thymoma: analysis of clinicopathologic features, treatment, and
      outcome.
AB  - OBJECTIVE AND METHODS: This study reports clinicopathologic features, treatment,
      and outcome of 30 recurrent thymomas out of 266 totally resected thymomas.
      RESULTS: The mean disease-free interval to recurrence was 86 months. Recurrence
      occurred less frequently and after a longer disease-free interval after resection
      of encapsulated versus invasive thymomas. The presence of associated myasthenia
      gravis did not affect recurrence proportion, disease-free interval, or survival
      after recurrence. A local recurrence occurred in 11 patients, 17 patients had a
      distant recurrence, and the extent of the recurrence could not be determined in 2
      cases. Surgical treatment of the recurrent tumor was attempted in 16 cases, and a
      total resection was possible in 10 cases; exclusive radiotherapy was done in 11
      cases. Overall 5- and 10-year survivals were 48% and 24%, respectively. In a
      univariate analysis, survival was significantly better in the presence of a local
      recurrence and in case of a total resection of the recurrent tumor. The use of
      adjuvant therapy after the resection of the initial thymoma had no effect on
      reducing the incidence of recurrence, in prolonging the disease-free interval, or
      in improving survival after the development of the recurrence. In a multivariate
      survival analysis, significant prognostic factors were the presence of a local
      recurrence and total resection of the recurrent tumor. CONCLUSIONS: Surgical
      resection is recommended in patients with recurrent thymoma. Local recurrence and
      total resection of the recurrent tumor are associated with excellent prognosis. A
      poor prognosis may be anticipated in the presence of distant recurrence and when
      radical surgical treatment is not done.

PMID- 9011703
TI  - Peritoneal dialysis in children after cardiopulmonary bypass.
AB  - OBJECTIVE: We reviewed 5 years' experience with peritoneal dialysis in children
      with acute renal failure after cardiac operations. We hypothesized that
      peritoneal dialysis is safe and effective in children with low-output cardiac
      failure after cardiac operations. RESULTS: Mortality in these patients with renal
      failure (n = 32) was 46.9%. Fluid removed by peritoneal dialysis was 48 +/- 28
      ml/kg per 24 hours. Most complications of peritoneal dialysis were minor,
      hyperglycemia being the most frequent (53.1%). Peritoneal infection was suspected
      in 25%. Bowel perforation developed in two patients. None of the complications
      required early termination of dialysis. Hemodynamics and pulmonary function
      improved continuously during the study period. CONCLUSION: The early institution
      of peritoneal dialysis in acute renal failure and low cardiac output after
      cardiac operations not only removes fluid, thus easing fluid restriction, but may
      also improve cardiopulmonary function.

PMID- 9011704
TI  - Cerebral oxygenation during cardiopulmonary bypass in children.
AB  - OBJECTIVE: Previous work has found cerebral oxygen extraction to decrease during
      hypothermic cardiopulmonary bypass in children. To elucidate cardiopulmonary
      bypass factors controlling cerebral oxygen extraction, we examined the effect of
      perfusate temperature, pump flow rate, and hematocrit value on cerebral
      hemoglobin-oxygen saturation as measured by near infrared spectroscopy. METHODS:
      Forty children less than 7 years of age scheduled for cardiac operations with
      continuous cardiopulmonary bypass were randomly assigned to warm bypass,
      hypothermic bypass, hypothermic low-flow bypass, or hypothermic low-hematocrit
      bypass. For warm bypass, arterial perfusate was 37 degrees C, hematocrit value
      23%, and pump flow 150 ml/kg per minute. Hypothermic bypass differed from warm
      bypass only in initial perfusate temperature (22 degrees C); hypothermic low-flow
      bypass and low-hematocrit bypass differed from hypothermic bypass only in pump
      flow (75 ml/kg per minute) and hematocrit value (16%), respectively. Cerebral
      oxygen saturation was recorded before bypass (baseline), during bypass, and for
      15 minutes after bypass had been discontinued. RESULTS: In the warm bypass group,
      cerebral oxygen saturation remained at baseline levels during and after bypass.
      In the hypothermic bypass group, cerebral oxygen saturation increased 20% +/- 2%
      during bypass cooling (p < 0.001), returned to baseline during bypass rewarming,
      and remained at baseline after bypass. In the hypothermic low-flow and
      hypothermic low-hematocrit bypass groups, cerebral oxygen saturation remained at
      baseline levels during bypass but increased 6% +/- 2% (p = 0.05) and 10% +/- 2%
      (p < 0.03), respectively, after bypass was discontinued. CONCLUSIONS: In
      children, cortical oxygen extraction is maintained during warm cardiopulmonary
      bypass at full flow and moderate hemodilution. Bypass cooling can decrease
      cortical oxygen extraction but requires a certain pump flow and hematocrit value
      to do so. Low-hematocrit hypothermic bypass and low-flow hypothermic bypass can
      also alter cortical oxygen extraction after discontinuation of cardiopulmonary
      bypass.

PMID- 9011706
TI  - Efficacy of transcranial motor-evoked myogenic potentials to detect spinal cord
      ischemia during operations for thoracoabdominal aneurysms.
AB  - OBJECTIVE: Motor-evoked myogenic potentials after transcranial electrical
      stimulation monitor the vulnerable motoneuronal system of the spinal cord. This
      study reports our initial experiences with motor-evoked potentials to assess the
      adequacy of spinal cord perfusion during operations for thoracoabdominal
      aneurysms. METHODS: In 20 patients undergoing thoracoabdominal aneurysm
      operations, myogenic motor-evoked potentials were recorded. In 18 patients
      retrograde aortic perfusion was used. When spinal cord ischemia was detected,
      distal flow or mean arterial pressure was increased in an attempt to restore cord
      perfusion. By means of sequential crossclamping, motor-evoked potentials were
      also used to identify intercostal or lumbar arteries that needed to be
      reimplanted. RESULTS: Reproducible motor-evoked potentials could be recorded in
      all patients. During retrograde perfusion, nine patients showed a rapid decrease
      in the amplitude of motor-evoked potentials to less than 25% of baseline,
      indicating spinal cord ischemia. In five patients ischemic changes in motor
      evoked potentials could be reversed by increasing distal and proximal blood
      pressures. In four patients ischemic changes during crossclamping necessitated
      segmental artery reimplantation. In three of these four patients intercostal or
      lumbar arteries were reattached. In one patient reimplantation of segmental
      arteries was not possible; this patient awoke paraplegic. Segmental arteries were
      ligated after confirmation of intact motor-evoked potentials during aortic
      clamping in eight patients. None of these patients had a neurologic deficit. The
      absence of motor-evoked potentials at the end of the procedure always indicated a
      postoperative motor deficit. CONCLUSION: During operations for thoracoabdominal
      aneurysms, monitoring of motor-evoked potentials is an effective technique to
      detect spinal cord ischemia within minutes. This modality can be used to guide
      the management of distal aortic perfusion techniques and may also help to
      identify segmental arteries that need to be reattached.

PMID- 9011705
TI  - Factors that influence the development of atrial flutter after the Fontan
      operation.
AB  - OBJECTIVES: Atrial flutter is a frequent, potentially fatal complication of the
      Fontan operation, but risk factors for its development are ill defined. We
      evaluated clinical features that might predict the development of atrial flutter
      in patients who had a Fontan operation. METHODS: We evaluated 334 early survivors
      of a Fontan operation done between April 1973 and July 1991 (mean follow-up, 5.0
      +/- 3.8 years). Evaluation included electrocardiography, Holter monitor
      recordings, and chart review. Modifications of the Fontan operation included an
      extracardiac conduit (n = 43), an atriopulmonary anastomosis (n = 117), or a
      total cavopulmonary anastomosis (n = 174). Patient, time, and procedure-related
      variables were analyzed with respect to the development of atrial flutter.
      RESULTS: Atrial flutter was identified in 54 (16%) patients at a mean of 5.3 +/-
      4.7 years (range 0 to 19.7 years) after Fontan operation. Atrial flutter
      developed sooner and was more likely to occur in patients who were older at the
      time of Fontan operation (12.4 +/- 7.6 vs 6.3 +/- 5.2 years; p < 0.001), had a
      longer follow-up interval (8.7 +/- 3.9 vs 4.4 +/- 3.4 years; p < 0.001), had a
      prior atrial septectomy or pulmonary artery reconstruction (p < 0.01), and had
      worse New York Heart Association class symptoms (p < 0.02). The presence of sinus
      node dysfunction was associated with a higher incidence of atrial flutter (p <
      0.001). Although there was a lower prevalence of atrial flutter in those patients
      with a total cavopulmonary anastomosis, the follow-up for this group was shorter.
      Anatomic diagnoses, perioperative hemodynamics, and other previous palliative
      operations were not associated with an increased incidence of atrial flutter.
      Multivariate analysis identified age at operation, duration of follow-up,
      extensive atrial baffling, and type of repair as factors associated with the
      development of atrial flutter after Fontan operation. CONCLUSION: Atrial flutter
      continues to develop with time after the Fontan operation. Further follow-up is
      necessary to determine whether a total cavopulmonary anastomosis reduces the
      incidence of atrial flutter.

PMID- 9011707
TI  - [A honorary doctor in a sparsely populated region...He follows his patients from
      the birth and may play at funerals].

PMID- 9011708
TI  - [A psychotherapist about physicians: reported for malpractice: "Return to work
      immediately. The most risky is to see oneself as a victim"].

PMID- 9011710
TI  - [A proposal on suicide-clinics. A philosophical basis for ethical morass].

PMID- 9011709
TI  - [Extend the care guarantee--don't eliminate it!].

PMID- 9011711
TI  - [A reported malpractice issue is an issue of the whole clinic!].

PMID- 9011712
TI  - [Save us from delirium and senile dementia!].

PMID- 9011713
TI  - [The health care system--is the current situation best?].

PMID- 9011714
TI  - [Neuroleptics, drug benefits and cost savings].

PMID- 9011715
TI  - [An alternative treatment in aortic reconstruction].

PMID- 9011716
TI  - [The HSAN focused on missed bacterial culture].

PMID- 9011717
TI  - [An unexpected verdict by the HSAN in a case of Achilles tendon rupture].

PMID- 9011718
TI  - [A center for women at risk is situated in Uppsala].

PMID- 9011720
TI  - [The integrity of physicians is questioned].

PMID- 9011719
TI  - [A strongly misleading picture of the needs of patients with dementia in the
      HSU2000 report].

PMID- 9011721
TI  - [Venous leg ulcers. A sign of unsuccessful prevention].

PMID- 9011722
TI  - [Edema in heart failure. A retrospect of therapeutic strategy during the last 50
      years].

PMID- 9011723
TI  - [The unconscious--basis for the clinical eye. Intuition and empathy play together
      in the deepness of the memory].

PMID- 9011725
TI  - [Lars Werko, a phenomenon in Swedish health care. The science must reach the
      patient in health care].

PMID- 9011724
TI  - [The competition at the annual meeting of the physicians: eleven works of art,
      eleven diagnoses].

PMID- 9011726
TI  - [Nicholas Culpeper, a 17th century physician of herbal medicine: "What grows in
      England will cure the English].

PMID- 9011727
TI  - [Death in the opera. Terrible mortality: murder, suicide, executions].

PMID- 9011728
TI  - [The museums of medical history in Stockholm. A journey time, space and
      feelings].

PMID- 9011729
TI  - [Psychiatric therapeutic methods in the old times. Opium, camphor and electric
      rays].

PMID- 9011730
TI  - [Two therapeutic models in venous leg ulcers are compared: better results with
      optimized compression].

PMID- 9011731
TI  - [Edward Jenner, his prayer was granted after 175 years. He was not perplexed by
      cow-pox...].

PMID- 9011732
TI  - [Hypochondriasis--a rhetoric of the body. The hypochondriac transfers internal
      painful points to external, more visible places].

PMID- 9011733
TI  - ["Motpol"--a school of writing critically of society which broke the isolation of
      medical professionals].

PMID- 9011734
TI  - Starve the tumour, save the patient.

PMID- 9011735
TI  - Need for pulmonary artery catheterisation guideline.

PMID- 9011736
TI  - [National consensus on hyperandrogenemia].
AB  - Croatian Endocrine Society and Croatian Academy of Medical Sciences organized
      Symposium on Hyperandrogenaemia on March 22nd, 1996. Different aspects of this
      syndrome were discussed: epidemiology, classification and clinical features,
      steroid biosynthesis in the adrenal gland and ovarium, the genetics of polycystic
      ovarian syndrome (PCOS), clinical significance of testosterone and
      dihydrotestosterone metabolism, androgen excess and metabolic syndrome (syndrome
      X), insulin disturbances in PCOS, increased risk for development of non insulin
      dependent diabetes mellitus, androgen effects on serum lipoproteins, insulin like
      growth factors and function of ovarium, Doppler parameters in PCOS, treatment of
      hyperandrogenaemia, skin changes in PCOS, tests for adrenal and ovarial function,
      arterial hypertension and hyperinsulinism. National Board of Hyperandrogenaemia
      has been elected.

PMID- 9011737
TI  - [The effect of osteogenic protein 1 (bone morphogenetic protein 7) on growth in
      long bones in rats].
AB  - Osteogenic protein-1 (OP-1; BMP-7) is a member of the bone morphogenetic protein
      subfamily. Since members of the TGF-beta superfamily have a role in tissue
      development, the influence of OP-1 on the growth of long bones in rats was
      examined. OP-1 was administered intraperitoneally during the fourteen days of
      experiment. Animals were double labeled with fluorescent bone markers seven and
      two days before the sacrifice. Femora were extracted and examined under UV light
      microscope to determine bone volume, trabecular appositional growth, growth rate
      and growth plate thickness. OP-1 was found to decrease trabecular appositional
      growth and the growth plate thickness without influencing the total bone volume.

PMID- 9011738
TI  - [Personal experience in the treatment of war injuries of the jaw and face at the
      Clinical Hospital Center in Rijeka].
AB  - In this paper we have presented 38 cases of wounded persons who had sustained war
      injuries in maxillo-facial and neck region. All of them were injured in Croatia
      during the war period of 1991 and 1992, and treated at the Maxillo-Facial Surgery
      Department of the Clinical Hospital of Rijeka. The wounded persons were observed
      and monitored from the moment of their injury through the first aid on the spot,
      up to the surgical treatment of the wounds, subsequent primary and secondary
      reconstruction, and the final medical treatment. This paper describes for wounded
      persons with injuries of bones and soft tissue of the face. In two thirds of the
      wounded persons with the primary medical treatment and reconstruction, the cure
      terminated, while in one third it was necessary to provide for a secondary
      reconstructive operation. At the end of the treatment, all the wounded persons
      were successfully cured, functionally and aesthetically restored, so they were
      able to leave the Clinic to return to their everyday life and work. Such result
      has been particularly gratifying because they were mostly young men.

PMID- 9011740
TI  - [The Cohen syndrome].
AB  - A girl with Cohen syndrome is presented. The diagnosis has been established on
      the basis of the characteristic face appearance with hypoplastic maxilla and
      mandible, open mouth, prominent maxillary central incisors, as well as
      characteristic appearance of extremities (narrow hands and feet), childhood
      obesity, hypotonia, and mental insufficiency. The girls also has the so-called
      "mottled retina". The attempts of weight reduction have been unsuccessful so far.

PMID- 9011739
TI  - [Dynamic aggregation of thrombocytes in acute myocardial infarct].
AB  - The dynamics of circulating platelet aggregates (CPA) in acute myocardial
      infarction (MI) was correlated to its extent, localization and clinical outcome.
      Creatine kinase (CK) and CPA were measured in 30 patients with acute MI 24 hours
      after its onset, and on the third, fifth and eighth day following the accident.
      Twelve patients had anteroseptal MI, another 12 had inferior, and the remaining 6
      had non-Q wave MI. 24 hours after the accident CPA values differed significantly
      between the three groups (p < 0.05). The values of CPA increased with increasing
      CK. In all the patients CPA and CK returned to normal or almost normal values on
      days 8 and 5 following MI, respectively. Eleven patients (37%) had heart failure:
      8 of them (73%) had anteroseptal MI and 3 had inferior MI (27%). In 10 patients
      with heart failure (91%) and only in 2 out of 19 patients without heart failure
      (10.5%), CPA peaked on days 3 or 5 after MI (p < 0.05). In all other patients CPA
      declined steadily from the initial value. These results suggest that platelet
      aggregability is significantly associated with the severity of MI and with heart
      failure.

PMID- 9011741
TI  - [60 years' of the modern hospital in Pozega].
AB  - The development of the hospital in Pozega, from medieval poor houses to the
      establishment of a modern hospital in 1936, is presented. In the late 19th and
      early 20th century, surgery departments were founded in many hospitals in
      Slavonia. The old town hospital built in 1836 did not meet the demands of medical
      work, and in the period from 1930 to 1936 a new hospital building was
      constructed. Since then, the hospital has played a major role in health education
      and promotion, prevention and treatment of disease, and training of medical
      staff. After 1961 new departments were established (pediatrics, gynecology,
      otorhinolaryngology), and in 1981 a new surgery was built with seven operation
      rooms, as well as a modern intensive care unit, delivery rooms etc. These
      developments contributed to good hospital functioning during the war in 1991
      1992. The hospital reconstruction with equipment renewal is now under way.
      Education of medical staff and scientific activities are continuing tasks which
      must accompany advances in medicine.

PMID- 9011742
TI  - [A visit to the St. Christopher Hospice in London and the Marie Curie Center in
      Liverpool].

PMID- 9011743
TI  - [Must patients with cancer suffer pain?].

PMID- 9011744
TI  - Gene structure and chromosomal localization of the mouse NMDA receptor channel
      subunits.
AB  - Multiple espilon subunits are major determinants of the diversity of the N-methyl
      D-aspartate (NMDA) receptor channel. The four epsilon subunit mRNAs exhibit
      distinct expression patterns in the brain. In an attempt to elucidate the
      molecular basis of selective and characteristic expression of the NMDA receptor
      channel subunits, we have isolated the gene encoding the mouse NMDA receptor
      epsilon 3 subunit and have determined its structural organization. The epsilon 3
      subunit gene spans 17.5 kb and consists of 14 exons. The major transcription
      start site is 439 bp upstream of the ATG initiation codon as determined by primer
      extension and S1 nucleas protection analyses. Two polyadenylation sites are 397
      (or 398) and 402 bp downstream of the termination codon. The 5'-flanking region
      of the epsilon 3 subunit gene contains GC-rich segments including consensus
      sequences for binding of the transcription factors Spl and EGR-1. The murine
      chromosomal locations of the five NMDA receptor channel subunits, the epsilon 1
      (Grin2a), epsilon 2 (Grin2b), epsilon 3 (Grin2c), epsilon 4 (Grin2d) and zeta 1
      (Grinl) subunits, were determined using an interspecific backcross mapping panel
      derived from crosses of [(C57BL/6JxM. spretus) F1xC57BL/6J] mice. Each of these
      genes mapped to a single chromosome location. The mapping results assigned the
      five loci to five different mouse autosomes, indicating that they have become
      well dispersed among mouse chromosomes.

PMID- 9011745
TI  - CDNA cloning of chick brain alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptors reveals conservation of structure, function and post
      transcriptional processes with mammalian receptors.
AB  - Several types of functional ionotropic glutamate receptor have been cloned in the
      recent years from the mammalian central nervous system, but till now, none from
      other vertebrate species. Here, we report the cloning and functional analysis of
      four chick brain cDNAs, coding for members of the alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) receptor subtype of glutamate receptors. These
      receptors are highly homologous to the mammalian GluR1-4 (A-D) receptors ( >
      90%), and conserve their post-transcriptional modifications. The flip/flop exons
      are conserved not only at the amino acid level but also at the nucleotide level,
      and the intron of GluR4 involved in the RNA editing of the R/G site displays a
      rat-chick sequence conservation of 95%. Significant sequence differences are
      found only in the region containing the immunogenic epitope of neuroactive anti
      GluR3 antibodies. Chick AMPA receptors are expressed in both the cerebrum and
      cerebellum. The ion channel activities of chick GluR1-4 were analyzed in Xenopus
      oocytes and found to be similar to those of mammalian AMPA receptors. Though
      their contribution to kainate binding activity in the cerebellum is minor, the
      profile of channel activity of the chick GluR1-4 suggests that they account for
      the kainatergic channel activity expressed by total chick cerebellar mRNAs.

PMID- 9011746
TI  - Differential effects of excitatory amino acids on mesencephalic neurons
      expressing either calretinin or tyrosine hydroxylase in primary cultures.
AB  - In mesencephalic primary cultures derived from E14 rat embryos, calretinin- and
      tyrosine hydroxylase-immunoreactive neurons comprised 2% and 5% of the total cell
      population, respectively, at 6-7 days in vitro. The number of calretinin
      immunoreactive neurons was unchanged after a 12- or 24-h exposure to 500 microM
      kainic acid (KA), but a 50% cell loss was detected after a 48-h exposure to KA.
      Tyrosine hydroxylase-immunoreactive neurons demonstrated a 50% and 67% cell loss
      at 24- and 48-h exposures to 500 microM KA. A 500 microM N-methyl-D-aspartic acid
      (NMDA) incubation for 24 h had no effect on calretinin-immunoreactive cell
      number, but did significantly reduce tyrosine hydroxylase-immunoreactive cell
      numbers by 26%. In tyrosine hydroxylase-immunoreactive cells, exposure to KA
      appeared to stimulate the retraction of the neuritic tree and to cause somatic
      swelling. In contrast, calretinin-immunoreactive neurons developed larger and
      more complex neuritic trees after a 24-h exposure to 500 microM KA but not NMDA.
      Immunohistochemical colocalization studies revealed that all tyrosine hydroxylase
      immunoreactive and the majority of calretinin-immunoreactive neurons expressed
      the glutamate receptor subunits GluR2-R3. Very low levels of NMDAR1 receptor
      subunits were detected on cells in this culture and GluR4 receptor subunits were
      not detectable. Our experiments showed that glutamate receptors present in both
      calretinin- and tyrosine hydroxylase-immunoreactive cells were functional, since
      phosphorylated cAMP/Ca2+ response element-binding protein levels were increased
      in both cell types after 10 or 30 min exposures to 500 microM KA. The present
      results indicate that in the mesencephalic cultures tyrosine hydroxylase
      immunoreactive cells are more vulnerable to KA excitotoxicity than calretinin
      immunoreactive neurons.

PMID- 9011747
TI  - Immediate early gene expression in cat visual cortex during and after the
      critical period: differences between EGR-1 and Fos proteins.
AB  - Immediate early gene (IEG) expression in the cat visual cortex is highly
      responsive to visual input and may initiate genetic mechanisms responsible for
      neuronal plasticity. The present study used immunohistochemical methods to
      address two issues regarding IEG expression in response to visual input. One was
      to define the differential response of distinct IEG families by comparing EGR-1
      (also termed zif-268, NGFI-A, and Krox-24) and Fos proteins. The second was to
      determine whether IEG expression, in addition to reflecting neural activity, is
      related to the state of plasticity by comparing young and adult visual cortex.
      Immunoreactivity of the two IEG proteins was compared between 5-week-old and
      adult cats under three conditions of visual input: ambient light to assess basal
      levels of expression, 1 week of darkness to assess the effect of reduced
      activity, and exposure to light after 1 week of darkness to determine rapid
      changes in expression as a result of visual input. At both ages, there were
      marked differences in the expression of the two IEG proteins. EGR-1 responded to
      visual input with sustained changes in its level of expression. It showed high
      basal levels, reduced expression in darkness, and a rapid return to high
      constitutive levels with the introduction of light. Fos showed a markedly
      different profile. It had very low basal expression which was not demonstrably
      affected by darkness and its principal response was a marked transient induction
      upon exposure to light after darkness. These unique changes in expression
      highlight the complex response across IEGs to environmental input and suggest a
      genetic "on/off' signaling mechanism. There were marked differences in the
      laminar distribution of EGR-1 and Fos proteins between young and adult cats. In
      young animals, cells in all visual cortical layers showed high levels of EGR-1
      and Fos proteins. In adults, immunostaining was largely specific to cells located
      above and below layer IV and only very faint labeling occurred within layer IV.
      These differences in laminar distribution between ages are inconsistent with a
      simple explanation of IEG expression in terms of neural activity level; rather,
      they suggest a relation between IEG expression and the state of plasticity in
      visual cortex.

PMID- 9011748
TI  - Structure of a parathyroid hormone/parathyroid hormone-related peptide receptor
      of the human cerebellum and functional expression in human neuroblastoma SK-N-MC
      cells.
AB  - Cloning and functional expression of a cDNA from the human cerebellum revealed a
      parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor
      protein of 593 amino acids, identical in sequence to the PTH/PTHrP receptor of
      the human kidney and an osteoblast-like cell line (Schipani et al.,
      Endocrinology, 132 (1993) 2157-2165). Expression of mRNA hybridizing with the
      cloned cDNA, indistinguishable in size on Northern blots from a 2.3 kb transcript
      in kidney and liver, was detected in eight brain areas. In situ hybridization
      histochemistry in rat brain tissue sections revealed predominant signals in the
      Purkinje cell layer of the cerebellum and in the mesencephalic nucleus of the
      trigeminal nerve. In human neuroblastoma (SK-N-MC) cells, stably transfected with
      the cloned cDNA, hPTH(1-84) and hPTH(1-34) displaced binding of 125 pM
      [125I][Tyr36]chPTHrP(1-36) to the PTH/PTHrP receptor with IC50 values of 4.0 +/-
      0.6 nM and 2.00 +/- 0.08 nM, and stimulated cyclic AMP accumulation with EC50
      values of 0.19 +/- 0.06 nM and 0.09 +/- 0.01 nM, respectively. 16 out of 48 cells
      responded to 100 nM hPTH(1-34) with a 2-10-fold transient increase of cytosolic
      free calcium concentrations. In conclusion, a PTH/PTHrP receptor, identified in
      the human cerebellum, has the primary structure of the corresponding receptors of
      kidney and bone. Expression in human neuroblastoma SK-N-MC cells revealed
      functional properties indistinguishable from those of non-neuronal tissues. The
      widespread distribution of PTHrP and its receptor in brain implies biological
      functions remaining to be elucidated.

PMID- 9011749
TI  - Nitric oxide-evoked [3H] gamma-aminobutyric acid release is mediated by two
      distinct release mechanisms.
AB  - Mechanisms underlying the release of [3H] gamma-aminobutyric acid (GABA) evoked
      by nitric oxide (NO) were investigated by use of primary cultured neurons
      prepared from the mouse cerebral cortex. NO generators such as sodium
      nitroprusside (SNP) and S-nitroso-N-a etylpenicillamine (SNAP) increased both
      [3H]GABA release from the neurons and [45Ca2+] influx into the neurons in a dose
      dependent manner, which was significantly diminished by hemoglobin. The removal
      of Ca2+ significantly reduced the NO-induced [3H]GABA release by about 50%.
      Nipecotic acid and 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1, 2, 5, 6
      tetrahydro-3- pyridinecarboxylic acid (NO-711), GABA uptake inhibitors dose
      dependently inhibited the NO-evoked [3H]GABA release in either the presence or
      absence of Ca2+. The concentration of these GABA uptake inhibitors to suppress
      the NO-induced release of [3H]GABA was sufficiently lower than that to exhibit
      the inhibition of [3H]GABA transport into the neurons. In addition, the NO-evoked
      [3H]GABA release was reduced by approximately 50% when total Na+ in incubation
      buffer was replaced with equimolar choline, and was also completely abolished by
      the removal of both Ca2+ and Na+. These results indicate that the release of
      [3H]GABA evoked by NO is mediated by two release mechanisms, a Ca2+ -dependent
      release system and the reverse process of the Ca2+ -independent and Na+ 
      dependent carrier-mediated GABA uptake system.

PMID- 9011750
TI  - Gap-43 message levels in anterior cerebellum in Alzheimer's disease.
AB  - We have previously reported that decreased growth-associated protein (GAP-43)
      message in frontal association cortex (area 9) of Alzheimer's disease (AD)
      patients is associated with increased density of neurons containing
      neurofibrillary tangles (NFTs) [9]. This finding leads to the hypothesis that
      decreased GAP-43 message in AD may be related to NFTs, rather than to some other
      aspect of AD pathology. Therefore, we predicted that in areas of brain unaffected
      by NFTs in AD the GAP-43 message levels should be similar to those of controls.
      The cerebellum is known to have a number of pathologies of AD, including diffuse
      plaques (DPs), microglial activation and reactive astrocytes. NFTs, however, are
      not typically found in the cerebellum. mRNA was extracted from anterior
      cerebellum of AD and control cases, Northern- and slot-blotted and hybridized
      against a GAP-43 probe. Poly(dT) and glucose-3-phosphate dehydrogenase probes
      were used for normalization. The average relative GAP-43 message level was 0.582
      in the AD cases and 0.448 in control cases. This 23% difference failed to reach
      statistical significance. Regression analysis within the AD group demonstrated
      that GAP-43 message level in cerebellar cortex was not significantly correlated
      with diffuse plaque density in cerebellar cortex. GAP-43 message levels in
      cerebellar cortex were also not correlated with summed density of neuritic
      plaques or summed density of NFTs in cortical regions-here used as an index of
      severity of disease. The data reported here also emphasize that the (NFT
      dependent) reduction in GAP-43 mRNA levels previously reported in frontal
      association cortex in Alzheimer's disease [9] appears to be region specific and
      not a general brain phenomenon. The preservation of normal GAP-43 message levels
      in the cerebellum in AD is consistent with the hypothesis that events related to
      NFT formation have a major impact on the expression of GAP-43 in Alzheimer's
      disease.

PMID- 9011751
TI  - Localization of mRNAs for Rlim-1, the rat Xlim-1 homolog, in the developing rat
      brain.
AB  - We studied the localization of Rlim-1 mRNAs, the rat Xlim-1 homolog, in the
      developing rat brain using in situ hybridization histochemistry. On embryonic day
      13 (E13), strong signals were observed in the most superficial layer of the
      telencephalon, the zonalimitans intrathalamica, the ventral thalamus, some nuclei
      of the hypothalamus, the tectum, the cerebellum, the lower brainstem and the
      spinal cord. In the above-mentioned regions except the cerebellum, the
      distribution pattern remained almost the same from embryonic stage to adulthood
      but the intensity of expression gradually decreased after birth. In the
      cerebellum, the distribution pattern changed. during development; all the
      primordium of cerebellum in E13, the external granular and the Purkinje cell
      layers in postnatal day 7 (P7), and only the Purkinje cell layer in the adult
      expressed positive signals. These results suggest that Rlim-1 may be involved in
      region specification.

PMID- 9011752
TI  - Dopamine transporter (Dat) and synaptic vesicle amine transporter (VMAT2) gene
      expression in the substantia nigra of control and Parkinson's disease.
AB  - The cellular expression of DAT mRNA and VMAT2 mRNA was investigated in sections
      of the human post-mortem substantia nigra in control and Parkinson's disease
      tissue using in situ hybridisation techniques. Short synthetic
      oligodeoxynucleotides were used to detect these gene transcripts at the cellular
      level. In the control human nigra, high levels of expression were seen in all sub
      divisions of the substantia nigra, especially within medial regions. By contrast,
      the level of expression of both DAT mRNA and VMAT2 mRNA was markedly reduced in
      Parkinson's disease; these reductions in hybridisation signal were associated
      with (i) a marked loss of dopamine-containing cells in the substantia nigra, and
      (ii) a reduction in both DAT and VMAT2 signal per cell in the remaining pigmented
      neurones. These disease-related decreases in the cellular abundance of both DAT
      and VMAT2 gene transcripts in the surviving cells of the parkinsonian nigra may
      reflect compensatory changes in catecholamine signalling or may be a consequence
      of neuronal dysfunction.

PMID- 9011753
TI  - Cloning and expression of a neuronal rat brain glutamate transporter.
AB  - Glutamate is the major excitatory transmitter in the mammalian central nervous
      system. Glutamate transporters, which keep the extracellular glutamate
      concentration low, are required both for normal brain function and for protecting
      neurons against harmful glutamatergic overstimulation. We have isolated the cDNA
      for a rat brain glutamate transporter (REAAC1) which has 90% amino acid and 86%
      nucleotide identity to the rabbit EAAC1. When REAAC1 was expressed in HeLa cells
      using a recombinant vaccinia-T7 virus expression system, a sodium dependent
      glutamate uptake was observed. The affinity of the carrier to various substrates
      was typical of brain "high affinity' glutamate uptake: threo-3-hydroxyaspartate,
      (R)-aspartate, (S)-glutamate and (S)-trans-pyrrolidine-2,4-dicarboxylic acid were
      strong inhibitors, but not (R)-glutamate or gamma-aminobutyrate. High resolution,
      non-radioactive in situ hybridization histochemistry in rat brain revealed the
      mRNA in several types of glutamatergic as well as non-glutamatergic neurons, but
      not in glial cells.

PMID- 9011754
TI  - Neuronal coexistence of trkB and glutamic acid decarboxylase67 mRNAs in rat
      hippocampus.
AB  - We have in earlier studies shown that brain derived neurotrophic factor (BDNF)
      mRNA expression is increased in the hippocampus following stimulation of
      excitatory cortical afferents and spatial learning. Furthermore, we have observed
      that excitatory influence in the hippocampus seems to increase in vivo release of
      gamma-aminobutyric acid (GABA), indicated by microdialysis perfusion of the CA1
      region. In this study we have investigated whether the receptor for BDNF, TrkB,
      may be expressed in GABA containing neurons in the CA1, thereby suggesting a
      possible role for BDNF in the trophic regulation of these neurons. We provide
      evidence of a neuronal coexistence of the mRNA encoding TrkB and glutamic acid
      decarboxylase, the key enzyme in the synthesis of GABA. This finding indicates
      that TrkB can be synthesized in GABA producing neurons in the hippocampus.

PMID- 9011756
TI  - Developmental regulation of alpha-tubulin mRNAs during the differentiation of
      cultured cerebellar granule cells.
AB  - T alpha 1 and T26 alpha-tubulin mRNA expression was examined during the
      differentiation of rat cerebellar granule cells in vitro and in situ. High levels
      of T alpha 1 transcript correlated with neurons extending processes and hence may
      implicate T alpha 1 with neuritogenesis. In comparison, T26 labeling was much
      less prominent, appeared more constitutive and was possibly associated with cell
      proliferation. Such profiles indicate that the different isotypes play different
      roles in the assembly and function of microtubules during neuronal
      differentiation.

PMID- 9011755
TI  - Transient expression of the basic helix-loop-helix protein NSCL-2 in the mouse
      cerebellum during postnatal development.
AB  - The spatio-temporal expression of the basic helix-loop-helix transcription factor
      NSCL-2 was analyzed in the postnatal development of the murine brain by in situ
      hybridization. We found that NSCL-2 is transiently expressed in the cerebellum.
      NSCL-2 was found exclusively in the premigratory zone of the external granule
      layer where postmitotic neurons undergo initial stages of neuronal
      differentiation. NSCL-2 expression was not detected in mature neurons. This
      pattern of expression suggests that NSCL-2 is critical for the onset of neuronal
      differentiation, but not for the maintenance of the differentiated state.

PMID- 9011757
TI  - Olfactory bulbectomy increases prepro-galanin mRNA levels in the rat locus
      coeruleus.
AB  - The effects of olfactory bulbectomy (OBX) on galanin (GAL) gene expression in the
      locus coeruleus (LC) were examined with quantitative in situ hybridization
      histochemistry. OBX increased prepro-GAL levels 3 and 14 days after surgery, as
      compared to sham-operated controls. Levels of mRNA encoding prepro-neuropeptide Y
      (NPY) were unchanged, and levels of mRNA encoding tyrosine hydroxylase (TH) were
      elevated in the LC only on day 3. The results indicate that GAL gene expression
      in the LC increases after lesioning a terminal field.

PMID- 9011758
TI  - Expression of three glutamate transporter subtype mRNAs in human brain regions
      and peripheral tissues.
AB  - We compared the expression of mRNAs for three human glutamate transporter
      subtypes in human central nervous system (CNS) and other organs by Northern blot
      analysis. hGLT-1 and hGLuT-1 mRNAs were most abundantly expressed in the brain,
      while hEAAC1 mRNA expression (3.8 kb and 2,4 kb) was strongest in peripheral
      organs. All subtype mRNAs were expressed throughout the CNS with hGLT-1
      predominant in frontal lobe, striatum and limbic areas, and hGluT-1 predominant
      in cerebellum.

PMID- 9011759
TI  - Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal
      medullary cells.
AB  - We examined expression of the 1,25-dihydroxyvitamin D3 [1,25-(OH)2 D3] receptors
      in chromaffin cells of the adrenal medulla and the effects of 1,25(OH)2 D3 on
      expression of the tyrosine hydroxylase (TH) gene. Accumulation of 1,25(OH)2 D3 in
      the nuclei of adrenal medullary cells, but not in the adrenal cortex, was
      observed in mice intravenously injected with radioactively labeled hormone.
      1,25(OH)2 D3 produced concentration-dependent increases in the TH mRNA levels in
      cultured bovine adrenal medullary cells (BAMC). The maximal increases (2-3-fold)
      occurred at 10(-8) M 1,25(OH)2 D3. Combined treatment with 1,25(OH)2 D3 and 20
      microM nicotine had no additive effect on TH mRNA levels suggesting that
      transsynaptic (nicotinic) and vitamin D (hormonal) stimulation of TH gene
      expression are mediated through converging mechanisms. Induction of TH mRNA by
      1,25(OH)2 D3 was not affected by calcium antagonist TMB-8. By increasing
      expression of the rate limiting enzyme in the catecholamine biosynthetic pathway,
      1,25-(OH)2 D3 may participate in the regulation of catecholamine production in
      adrenal chromaffin cells. This regulation provides mechanisms through which
      1,25(OH)2 D3 may control response and adaptation to stress.

PMID- 9011760
TI  - Elevated tyrosine hydroxylase mRNA levels in medulla oblongata of spontaneously
      hypertensive rats.
AB  - The present study has investigated the expression of tyrosine hydroxylase (TH)
      mRNA and its activity in medulla oblongata of spontaneously hypertensive rats
      (SHR) and Wistar Kyoto rats (WKY). The TH mRNA levels were determined by Northern
      blot and dot blot analyses. The TH activity and the expression of TH mRNA in
      medulla oblongata of SHR were significantly higher than those of WKY. These
      results suggest that the hypertension of SHR may be related to the high activity
      of TH due to the high level of TH mRNA which increases norepinephrine levels in
      the medulla oblongata.

PMID- 9011761
TI  - Distribution of the mRNA for protein phosphatase T in rat brain.
AB  - We have recently cloned a novel protein serine/threonine phosphatase (PPT) from
      rat mRNA which is predominantly expressed in the brain (Becker et al., J. Biol.
      Chem., 269 (1994) 22586-22592). In the present study, the regional distribution
      of PPT mRNA in the brain of adult rats was characterized by in situ hybridization
      histochemistry. PPT mRNA was found to be differentially expressed throughout the
      rat brain. Highest transcript levels were found in specific neuronal populations
      (hippocampus, piriform cortex, taenia tecta, medial habenula, granular cell layer
      of the cerebellum) as well as in the choroid plexus of the third and lateral
      ventricles. In contrast, expression levels in some brain areas, e.g., caudate
      putamen and white matter, were beyond the detection limit of in situ
      hybridization. The pattern of expression of PPT in rat brain differs from that of
      other protein serine/threonine phosphatases and may reflect specific functions of
      this phosphatase.

PMID- 9011762
TI  - G alpha q/11 mediates neurotensin excitation of substantia nigra dopaminergic
      neurons.
AB  - Using acutely dissociated substantia nigra pars compacta (SNC) dopaminergic (DA)
      neurons, our previous studies indicated that neurotensin (NT) excites SNC DA
      neurons by increasing the cationic conductance and reducing the inwardly
      rectifying K+ conductance. Further investigation also revealed that pertussis
      toxin (PTX)- insensitive G-proteins mediate neurotensin modulation of cation and
      potassium channels. G alpha q and G alpha 11 are widely distributed in various
      tissues including the brain and likely to mediate PTX-insensitive signal
      transductions in the nervous system. In this study, two different experiments
      were conducted to test the hypothesis that G alpha q/11 mediates neurotensin
      regulation of the cationic and K+ conductances. First, we investigated the
      expression of G alpha q and G alpha 11 mRNAs in NT-responsive SNC DA neurons by
      combining whole-cell patch-clamp recordings with single-cell reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay. After recording NT-evoked
      membrane currents, the cellular content was harvested from single neurons and
      used as the template for the subsequent RT-PCR analysis. Both G alpha q and G
      alpha 11 mRNAs were present in all SNC DA neurons that responded to neurotensin.
      SNC DA neurons were also internally dialyzed with an antibody directed against
      the common C-terminus of G alpha q and G alpha 11 during whole-cell recordings.
      In DA neurons perfused with the anti-G alpha q/11 antiserum, neurotensin failed
      to evoke inward currents resulting from the opening of cation channels and the
      closure of inward rectifier K+ channels. It is concluded that NT modulation of
      cation and inward rectifier K+ channels in SNC DA neurons is transduced by G
      alpha q and/or G alpha 11.

PMID- 9011763
TI  - Melanocortin receptors mediate alpha-MSH-induced stimulation of neurite outgrowth
      in neuro 2A cells.
AB  - Melanocortins (MC), neuropeptides derived from pro-opiomelanocortin, have been
      implicated in enhancing neurite outgrowth via an as yet unknown mechanism.
      Recently, five MC receptors have been identified, three of which, the MC3-R, the
      MC4-R and the MC5-R, are expressed in the nervous system. In this study, alpha
      MSH and the melanocortin analog [D-Phe7]ACTH (4-10) were able to stimulate
      neurite outgrowth in the neuroblastoma cell line Neuro 2A. ACTH (4-10), gamma2
      MSH and ORG2766 were inactive. In addition, the MC4-R antagonist [D-Arg8]ACTH (4
      10), inhibited the alpha-MSH effect, indicating that the MC4-R mediated
      stimulation of neurite outgrowth by alpha-MSH. Indeed, the presence of MC4-R mRNA
      in Neuro 2A cells was demonstrated by a RNase protection assay. Heterologous
      expression of the MC5-R in Neuro 2A cells lead to the recruitment of a
      responsiveness to gamma2-MSH, but did not increase the effect of alpha-MSH on
      neurite outgrowth. This finding indicated that the function of MC4-R can also be
      exerted by another MC receptor, suggesting that the coupling to Gs, which they
      have in common, plays an essential role in the neurite outgrowth promoting
      effect. This was further substantiated by the fact that forskolin treatment per
      se induced neurite outgrowth in a similar fashion. These data imply that the
      neurotrophic properties of alpha-MSH are likely to result from Gs-coupled MC
      receptor activity in neuronal cells.

PMID- 9011764
TI  - Cloning and expression of a novel gene for a protein with leucine-rich repeats in
      the developing mouse nervous system.
AB  - In a variety of organisms from yeast to humans, members of the leucine-rich
      repeat (LRR) family, in which one repeal consists of 24 amino acids and leucine
      residues appear regularly, have been shown to be involved in protein-protein
      interactions. In Drosophila, members of this family have significant functions in
      neural development. It is thus possible that similar molecules play a crucial
      role in the morphogenesis of the mammalian nervous system. Using a human brain
      cDNA fragment encoding an LRR as a probe, we have isolated a mouse brain cDNA
      which encodes a new LRR protein, NLRR-3 protein. The isolated cDNA is 3350 bp
      long including one open reading frame encoding a protein of 707 amino acids, the
      deduced amino acid sequence of which has a signal peptide and a transmembrane
      region. The NLRR-3 protein also contains an RGD sequence and 11 LRRs with amino-
      and carboxy-terminal LRR-flanking regions which are conserved among adhesive
      proteins and signal-transducing receptors in this family. Northern-blot analysis
      revealed strong expression of an approx. 4.2 kb NLRR-3 mRNA in the brain from E17
      to P7 and weak expression in adults. There in situ hybridization analysis
      demonstrated that NLRR-3 mRNA was expressed in the brain, in which stronger
      expression was localized in the ventricular zone and anlage of thalamus, spinal
      cord, and dorsal root ganglion in E11-17 cerebellum, and cerebral cortex in
      adults. The molecular structure in addition to the transient and localized
      expression suggests that the NLRR-3 protein plays a role in the development and
      maintenance of the nervous system by protein-protein interactions.

PMID- 9011765
TI  - Adrenalectomy enhances pro-inflammatory cytokines gene expression, in the spleen,
      pituitary and brain of mice in response to lipopolysaccharide.
AB  - To assess the possible influence of endogenous glucocorticoids on cytokine
      expression in the brain, adrenalectomized mice and sham operated mice were
      injected with saline or lipopolysaccharide (LPS, 10 micrograms/mouse,
      subcutaneously) and the levels of transcripts for IL-1 alpha, IL-1 beta, IL-1ra,
      IL-6 and tumor necrosis factor-alpha (TNF alpha) were determined 2 h after
      treatment in the spleen, pituitary, hypothalamus, hippocampus and striatum, using
      semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).
      Levels of IL-1 beta were measured by ELISA in plasma and tissues of mice
      sacrificed after the administration of LPS or saline. LPS induced the expression
      of pro-inflammatory cytokines at the mRNA level in all tissues under
      investigation, except for TNF alpha in the hippocampus. This effect was
      potentiated by adrenalectomy in the spleen for IL-1 alpha and IL-1ra, the
      pituitary for cytokines other than IL-1ra, the hypothalamus for all cytokines,
      the hippocampus for cytokines other than TNF alpha, and the striatum for IL-1
      alpha and IL-6. In saline-treated mice, adrenalectomy increased IL-1 alpha and IL
      1 beta gene expression in the hypothalamus and IL-1 alpha gene expression in the
      hippocampus and striatum. LPS increased plasma and tissue levels of IL-1 beta, as
      determined by ELISA, and this effect was potentiated by adrenalectomy in plasma
      and tissues other than the spleen. These results can be interpreted to suggest
      that endogenous glucocorticoids regulate the neural components of the host
      response to infection and inflammation by inhibiting cytokine expression in
      peripheral organs and the brain.

PMID- 9011766
TI  - Molecular characterization of dendritically localized transcripts encoding MAP2.
AB  - Transcripts encoding high molecular weight (Hwt) isoforms of microtubule
      associated protein 2 (MAP2) have been localized in the dendritic compartment of
      neurons. In contrast, nearly all other neuronal messages, including transcripts
      encoding low molecular weight (Lwt) MAP2 isoforms, are restricted to cell somas.
      The mechanisms underlying the dendritic localization of Hwt-MAP2 transcripts are
      not known. In non-neuronal systems, mRNAs, are localized via signal sequences
      situated in their 3' untranslated regions (3' UTRs). In this study, we have
      localized the putative dendritic targeting element (DTE) in Hwt-MAP2 mRNAs by
      comparing the nucleotide sequences of the somatically localized 6 kb Lwt-MAP2
      transcripts with the dendritcally localized 9 kb messages. Our analysis shows
      that both 6 kb and 9 kb transcripts have identical 3' - and 5'- UTRs, precluding
      the possibility that the DTE lies in these regions. Within the coding region a
      single segment that is unique to 9 kb Hwt MAP2 transcripts was identified. These
      findings suggest that the DTE lies within the 4 kb RNA segment that encodes the
      projection domain of Hwt-MAP2.

PMID- 9011767
TI  - Fibroblast growth factor receptor 1 in the adrenal gland and PC12 cells:
      developmental expression and regulation by extrinsic molecules.
AB  - In the present study we have analyzed the expression of fibroblast growth factor
      receptor 1 (FGFR-1) mRNA in the developing and adult rat adrenal gland and in
      PC12 cells under different culture conditions. For this purpose a sensitive
      ribonuclease protection assay using 33P-labelled riboprobes was established. 33P
      labelled riboprobes show a high resolution and are relatively easy to handle.
      FGFR-1 mRNA was found to be present in the postnatal and adult adrenal gland. In
      the cortex high levels of FGFR-1 mRNA were detected at postnatal day (P) 1 and
      P8, during the third week the mRNA levels declined, and reached low levels during
      adulthood. PC12 cells also contained detectable amounts of FGFR-1 mRNA. With the
      exception of NGF, however, the different treatment procedures did not affect FGFR
      1 mRNA levels. The expression pattern of the FGFR-1 transcript matches that of
      the expression of FGF-2 and of the mitotic activity in the developing and adult
      cortex. This supports the idea that FGF-2 might act as an autocrine mitogen for
      adrenocortical cells. In the medulla FGFR-1 mRNA levels were low at the first 3
      postnatal weeks and increased towards the adult. In accordance with the
      developing expression pattern of FGF-2 in the medulla and in vitro effects of
      this protein on chromaffin and PC12 cells an autocrine/paracrine role as a
      maintenance and differentiation factor for chromaffin cells is conceivable.

PMID- 9011768
TI  - Positive and negative elements contribute to the cell-specific expression of the
      rat dopamine beta-hydroxylase gene.
AB  - Dopamine beta-hydroxylase catalyzes the final step in noradrenaline synthesis and
      is expressed exclusively in noradrenergic and adrenergic cells. In order to
      identify elements within the dopamine beta-hydroxylase (DBH) gene which
      contribute to the regulation of tissue-specific expression, we have analyzed the
      expression of the rat DBH promoter by transient transfection in both DBH
      expressing and non-expressing cell lines. We have found that 1 kilobase of the
      DBH promoter can direct expression of the luciferase reporter gene in the DBH
      expressing PC12, CATH.a, and SK-N-SH cell lines, but not in the non-DBH
      expressing C6 glioma or CA77 cell lines. This activity was localized to a region
      between -133 and -173 upstream of the transcription start site. This element,
      however, also directed expression in non-DBH-expressing cell lines, but was
      inhibited when sequences between -212 and -388 were included. This inhibitory
      region contains sequences homologous to a silencer element recently identified in
      the human DBH gene, and shares homology with other previously identified silencer
      elements. Gel retardation experiments demonstrate that the rat DBH inhibitory
      region and the silencer elements found in the rat sodium type II channel and
      SCG10 genes bind a similar factor. The region between -133 and -173, which
      contains a consensus cyclic AMP response element (CRE), was also found to be
      responsive to cAMP in both DBH-expressing and non-expressing cells. Inclusion of
      sequences between -173 and -190 diminished the cAMP induction in PC12 cells, and
      nearly abolished the induction in C6 and CA77 cells, suggesting the presence of
      an additional negative element which inhibits cAMP induction in non-DBH
      expressing cells. DNA binding assays using antibodies to CRE binding protein
      related transcription factors identified ATF-1 binding to the rat DBH-CRE, and
      further suggest that inhibition of cAMP regulation may be due to inhibition of
      ATF-1 binding by an additional factor, which binds to the DBH promoter
      immediately upstream of the CRE. These results demonstrate the importance of both
      positive and negative regulatory elements in the regulation of tissue-specific
      expression of the rat DBH gene.

PMID- 9011769
TI  - Ca2+ entry following store depletion in SH-SY5Y neuroblastoma cells.
AB  - Ca2+ entry following Ca2+ store depletion was examined in the human neuroblastoma
      cell line, SH-SY5Y, by measuring the concentration of intracellular free Ca2+
      ([Ca2+]i) with fura-2. Application of the muscarinic agonist oxotremorine-M (oxo
      M) caused an increase in [Ca2+]i. This consisted of a peak, mediated by release
      of Ca2+ from internal stores followed by a sustained plateau, mediated by Ca2+
      entry across the plasma membrane. The Ca2+ entry resulted from depletion of
      intracellular Ca2+ stores This pathway was further characterized in the presence
      of thapsigargin, an inhibitor of the Ca2+ ATPase involved in replenishing IP3
      sensitive stores. Stores were first depleted with oxo-M and thapsigargin in the
      absence of extracellular Ca2+. After washout of oxo-M, subsequent exposure to
      Ca2+ evoked reproducible increases in [Ca2+]i. Application of oxo-M plus Ca2+ had
      little effect on the increases in [Ca2+]i, indicating that in SH-SY5Y cells,
      agonist-dependent pathways contribute little to Ca2+ entry following store
      depletion. Mn2+, Sr2+ and Ba2+ were permeable through this pathway. Mn2+ and Ba2+
      also showed slight permeability in the absence of store depletion. Ca2+ entry
      following store depletion was blocked by La3+ (IC50 = 75 nM) and by SKF 96365.
      La3+ blocked Mn2+ entry through the pathway activated by store depletion but did
      not affect basal Mn2+ permeability. These results indicate that SH-SY5Y
      neuroblastoma cells have an agonist-independent Ca2+ entry pathway activated by
      store depletion.

PMID- 9011770
TI  - [Blood coagulation self-control].

PMID- 9011771
TI  - [Leukotriene receptor antagonists].

PMID- 9011772
TI  - [Antioxidants in therapy of lung diseases. Concepts and reality].

PMID- 9011773
TI  - [Stress and cognition].

PMID- 9011774
TI  - 1997 revised guidelines for performing CD4+ T-cell determinations in persons
      infected with human immunodeficiency virus (HIV). Centers for Disease Control and
      Prevention.
AB  - These revised guidelines were developed by CDC for laboratories performing
      lymphocyte immunophenotyping assays in human immunodeficiency virus-infected
      persons. This report updates previous recommendations (MMWR 43[No. RR-3]) and
      reflects current technology in a field that is rapidly changing. The
      recommendations address laboratory safety, specimen collection, specimen
      transport, maintenance of specimen integrity, specimen processing, flow cytometer
      quality control, sample analyses, data analysis, data storage, data reporting,
      and quality assurance.

PMID- 9011775
TI  - Injuries and deaths associated with use of snowmobiles--Maine, 1991-1996.
AB  - During the 1995-96 winter season (i.e., November 1995 through April 1996), both
      the Maine Department of Inland Fisheries and Wildlife (DIFW) and the Maine Office
      of the Chief Medical Examiner (OCME) detected an increase in deaths associated
      with snowmobile use in Maine. From the fall of 1991 through the spring of 1995,
      three to eight snowmobile-related deaths occurred each winter season (mean: 5.4
      per winter season); during the 1995-96 winter season, 12 deaths were recorded-
      the largest number of snowmobile-related deaths in 25 years. In addition, from
      1991 through 1996, the number of registered snowmobiles increased from 61,641 to
      a record high of 76,477, respectively, and the death rate per registered vehicle
      in 1996 was higher than in any of the previous 5 years. To assist in the
      development and evaluation of strategies to prevent injury and death associated
      with the use of snowmobiles in Maine, the Bureau of Health, Maine Department of
      Human Services (BOH), collaborated with DIFW and OCME to examine data about fatal
      and nonfatal injuries associated with use of snowmobiles from 1991 through 1996.
      This report summarizes the results of this analysis and recommends strategies for
      preventing such deaths and injuries.

PMID- 9011776
TI  - Outbreaks of Escherichia coli O157:H7 infection and cryptosporidiosis associated
      with drinking unpasteurized apple cider--Connecticut and New York, October 1996.
AB  - In October 1996, unpasteurized apple cider or juice was associated with three
      outbreaks of gastrointestinal illness. In the Western United States, an outbreak
      of Escherichia coli O157:H7 infections associated with unpasteurized commercial
      apple juice caused illness in 66 persons and one death. In addition, one outbreak
      of apple cider-related E. coli O157:H7 infections and another of cider-related
      Cryptosporidium parvum infections occurred in the Northeast. Apple cider is a
      traditional beverage produced and consumed in the fall. Cider often is
      manufactured locally at small cider mills where apples are crushed in presses,
      and the cider frequently is not pasteurized before sale. This report summarizes
      the clinical and epidemiologic features of the two apple cider-related outbreaks,
      which suggest that current practices for producing apple cider may not be
      adequate to prevent microbial contamination.

PMID- 9011777
TI  - Traumatic brain injury--Colorado, Missouri, Oklahoma, and Utah, 1990-1993.
AB  - In 1992, traumatic brain injuries (TBIs) accounted for 34% of all injury deaths
      in the United States. To provide current estimates of TBI-associated morbidity
      and deaths, CDC has developed guidelines for public health agencies to use for
      TBI surveillance. This report describes recent findings from Colorado, Missouri,
      Oklahoma, and Utah based on these guidelines. These findings indicate a decrease
      in the annual rate of TBI and that rates of TBI are highest in association with
      falls and motor-vehicle crashes.

PMID- 9011778
TI  - Evaluation of safety devices for preventing percutaneous injuries among health
      care workers during phlebotomy procedures--Minneapolis-St. Paul, New York City,
      and San Francisco, 1993-1995.
AB  - Health-care workers (HCWs) are at risk for infections with bloodborne pathogens
      resulting from occupational exposures to blood through percutaneous injuries
      (PIs). Phlebotomy, one of the most commonly performed medical procedures, has
      been associated with 13% - 62% of injuries reported to hospital occupational
      health services and 20 (39%) of the 51 documented episodes of occupationally
      acquired human immunodeficiency virus (HIV) infection reported in the United
      States (CDC, unpublished data, 1996). Although safety devices designed to prevent
      PIs associated with phlebotomy have been available for use in the United States,
      clinical evaluation of these devices has been difficult because 1) ascertainment
      of PIs is difficult (many injuries are unreported, and observation of all
      procedures is impractical because phlebotomy is performed throughout the hospital
      by different groups of HCWs at all hours), 2) data to calculate PI rates (i.e.,
      the number of phlebotomies performed and devices used) are not routinely
      available, 3) a large number of phlebotomies must be evaluated because of the low
      rates of phlebotomy-related PI and 4) rates of safety-feature activation are
      difficult to assess. This report summarizes a collaborative study by CDC and six
      hospitals to evaluate safety devices for phlebotomy. The findings indicate that
      use of safety devices significantly reduced phlebotomy-related PI rates while
      having minimal clinically apparent adverse effects on patient care.

PMID- 9011779
TI  - Evaluation of blunt suture needles in preventing percutaneous injuries among
      health-care workers during gynecologic surgical procedures--New York City, March
      1993-June 1994.
AB  - Infections with bloodborne pathogens resulting from exposures to blood through
      percutaneous injuries (PIs) (e.g., needlestick injuries and cuts with sharp
      objects) are an occupational hazard for health-care workers (HCWs). PIs have been
      reported during 1% - 15% of surgical procedures, mostly associated with suturing.
      Most suturing is done using curved suture needles, although straight needles are
      used by some surgeons for suturing skin. Blunt suture needles (curved suture
      needles that have a relatively blunt tip) may be less likely to cause PIs because
      they do not easily penetrate skin. Based on small studies and anecdotal
      experience, blunt suture needles appear able to replace conventional curved
      suture needles for suturing many tissues, although they may require more pressure
      to penetrate the tissues. This report summarizes results of a study in which CDC
      collaborated with three teaching hospitals in New York City during 1993-1994 to
      evaluate a safety device (a blunt suture needle) in gynecologic surgery. The
      findings indicate that use of blunt needles was associated with statistically
      significant reductions in PI rates, minimal clinically apparent adverse effects
      on patient care, and general acceptance by gynecologic surgeons in these
      hospitals.

PMID- 9011780
TI  - Q fever outbreak--Germany, 1996.
AB  - In May 1996, the Health Department of Marburg-Biedenkopf in Marburg, Hessen,
      Germany, was notified of a cluster of persons with high and persistent fever who
      resided in a rural town (Rollshausen [1996 population:300]) and in five
      surrounding towns approximately 0.5-2.0 miles from Rollshausen, in the district
      of Lohra. Serologic testing of some patients by local health authorities
      suggested acute Q fever. In Germany, Q fever is a reportable disease and 27-100
      cases are reported annually; during 1995, no cases had been reported from Lohra.
      In July 1996, the Robert Koch Institute (RKI) was invited to assist in an
      investigation of this cluster. This report summarizes the investigation of this
      outbreak, which indicated a high attack rate of Q fever in persons residing near
      the zoonotic origin of infection.

PMID- 9011781
TI  - Update: pulmonary hemorrhage/hemosiderosis among infants--Cleveland, Ohio, 1993
      1996.
AB  - In November 1994, private physicians and public health officials in Cleveland,
      Ohio, and CDC reported a cluster of eight cases of acute pulmonary
      hemorrhage/hemosiderosis that had occurred during January 1993-November 1994
      among infants in one area of the city. Two additional cases were identified in
      December 1994. All 10 infants lived within seven contiguous postal tracts in
      eastern metropolitan Cleveland. Pulmonary hemorrhages recurred in five of the
      infants after they returned to their homes shortly after hospital discharge; one
      infant died as a result of pulmonary hemorrhage. This report summarizes the
      findings of the follow-up investigation, including a case-control study and an
      assessment by the county coroner of cases of infant death. These findings
      documented an association between acute pulmonary hemorrhage/hemosiderosis in
      this cluster of cases and mold growth in their water-damaged homes.

PMID- 9011782
TI  - Recommended childhood immunization schedule--United States, 1997.
AB  - Since publication of the recommended childhood immunization schedule in July
      1996, the Advisory Committee on Immunization Practices (ACIP), the American
      Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP)
      have made important changes in recommendations for preventing pertussis and
      poliomyelitis. Following the licensure of two acellular pertussis vaccines for
      infants, the advisory groups now recommend use of acellular pertussis vaccine
      (Tripedia or ACEL-IMUNE) as the preferred vaccine for pertussis vaccination for
      infants beginning at age 2 months. To reduce the risk for vaccine-associated
      paralytic poliomyelitis (VAPP), recommendations for poliovirus vaccination have
      expanded the use of inactivated poliovirus vaccine (IPV) by providing three
      options for poliovirus vaccination (sequential IPV/oral poliovirus vaccine [OPV],
      all IPV, or all OPV). In addition, a combination Haemophilus influenzae type b
      (Hib) and hepatitis B vaccine and a combination diphtheria and tetanus toxoids
      and acellular pertussis vaccine (DTaP) and Hib vaccine have been licensed for use
      in certain situations. This report presents the recommended childhood
      immunization schedule for 1997 and explains the changes that have occurred since
      the last publication of the schedule.

PMID- 9011783
TI  - Measurement of residual leukemia during remission in childhood acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Complete remission of B-precursor acute lymphoblastic leukemia (ALL)
      has traditionally been defined as the near absence of lymphoblasts in a light
      microscopical examination of stained bone marrow smears, but a patient in
      remission may still harbor up to 10(10) leukemia cells. We investigated whether
      there is a relation between the outcome of treatment and submicroscopic evidence
      of residual disease. METHODS: We conducted a prospective study of patients during
      a first clinical remission using a quantitative polymerase-chain-reaction (PCR)
      assay capable of detecting 1 viable leukemia cell among 200,000 normal marrow
      mononuclear cells and a clonogenic blast-colony assay. Bone marrow specimens from
      24 children were sequentially evaluated during a five-year period, and the
      results were compared with the clinical outcome. RESULTS: Seven patients relapsed
      and 17 remained in remission 2 to 35 months after the completion of treatment.
      The levels of residual leukemia-cell DNA in the two groups were significantly
      different (P<0.001; 95 percent confidence interval for the difference in the mean
      log-transformed ratio of leukemia-cell DNA to normal bone marrow-cell DNA, 0.38
      to 1.28). Autoregression analyses identified trends for individual patients that
      were associated with relapse. Despite continued remission in 17 patients,
      evidence of residual leukemia was detected by PCR in 15 and by both PCR and blast
      colony assays in 7. CONCLUSIONS: Molecular signs of residual leukemia can persist
      up to 35 months after the cessation of chemotherapy in children with ALL in
      remission. This suggests that eradication of all leukemia cells may not be a
      prerequisite for cure.

PMID- 9011784
TI  - A controlled trial of immunotherapy for asthma in allergic children.
AB  - BACKGROUND: Injections of allergens are widely prescribed for patients with
      asthma, but little is known about the effectiveness of immunotherapy. METHODS: We
      conducted a double-blind, placebo-controlled trial of multiple-allergen
      immunotherapy in 121 allergic children with moderate-to-severe, perennial asthma.
      The children, who required daily medication for their asthma, were randomly
      assigned to receive subcutaneous injections of either a mixture of up to seven
      aeroallergen extracts or a placebo. Maintenance injections were continued for 18
      months or longer. Medications were adjusted every two to three weeks on the basis
      of peak flow rates and symptoms. The principal outcome was the daily medication
      score. Bronchial sensitivity to methacholine (the concentration provoking a 20
      percent decrease in the forced expiratory volume in one second [PC20]) was
      measured twice yearly. RESULTS: The median medication score declined from 5.4 to
      4.9 in the immunotherapy group (P<0.001) and from 5.2 to 5.0 in the placebo group
      (P<0.001), but there was no significant difference between the groups (P>0.6).
      The number of days on which oral corticosteroids were used was similar in the two
      groups. Partial or complete remission of asthma occurred in 31 percent of the
      immunotherapy group and in 28 percent of the placebo group (P>0.5). There was no
      difference between the groups in the use of medical care, symptoms, or peak flow
      rates. The median PC20 increased significantly in both groups, but again with no
      difference between the two groups. CONCLUSIONS: Immunotherapy with injections of
      allergens for over two years was of no discernible benefit in allergic children
      with perennial asthma who were receiving appropriate medical treatment.

PMID- 9011786
TI  - Spontaneous remission in a patient with chronic myelogenous leukemia.

PMID- 9011785
TI  - Cost effectiveness of simvastatin treatment to lower cholesterol levels in
      patients with coronary heart disease. Scandinavian Simvastatin Survival Study
      Group.
AB  - BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) showed that lowering
      cholesterol levels with simvastatin reduces mortality and morbidity in patients
      with angina pectoris or previous acute myocardial infarction. Before the
      widespread use of cholesterol-lowering drugs in such patients is recommended, its
      cost effectiveness should be demonstrated. We estimated the cost effectiveness of
      simvastatin treatment to lower cholesterol levels in relation to the age, sex,
      and cholesterol level before treatment of patients with coronary heart disease.
      METHODS: We estimated the cost per year of life gained with simvastatin therapy.
      To model the increased life expectancy, hazard functions from 4S were used. The
      costs studied included those of the intervention and the direct and indirect
      costs associated with morbidity from coronary causes. We prepared separate
      estimates for men and women at various ages (from 35 to 70 years) and total
      cholesterol levels before treatment (213 to 309 mg per deciliter). RESULTS: In
      the analysis limited to direct costs, the cost of each year of life gained ranged
      from $3,800 for 70-year-old men with 309 mg of cholesterol per deciliter to
      $27,400 for 35-year-old women with 213 mg of cholesterol per deciliter. When we
      included indirect costs, the results ranged from a savings in the youngest
      patients to a cost of $13,300 per year of life gained in 70-year-old women with
      213 mg of cholesterol per deciliter. CONCLUSIONS: In patients with coronary heart
      disease, simvastatin therapy is cost effective among both men and women at the
      ages and cholesterol levels studied.

PMID- 9011787
TI  - Images in clinical medicine. Meningioma.

PMID- 9011788
TI  - Management of insomnia.

PMID- 9011789
TI  - The treatment of chronic viral hepatitis.

PMID- 9011790
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 4-1997. A 37-year-old man with AIDS and wheezing refractory to
      bronchodilator medication.

PMID- 9011791
TI  - Federal foolishness and marijuana.

PMID- 9011792
TI  - Silence of the leukemic clone.

PMID- 9011793
TI  - Practical experiences in obtaining informed consent for a vaccine trial in rural
      Africa.

PMID- 9011794
TI  - Multimodal therapy for esophageal adenocarcinoma.

PMID- 9011795
TI  - Multimodal therapy for esophageal adenocarcinoma.

PMID- 9011796
TI  - Multimodal therapy for esophageal adenocarcinoma.

PMID- 9011798
TI  - Case 26-1996: hypersensitivity to carbamazepine.

PMID- 9011797
TI  - Case 26-1996: hypersensitivity to carbamazepine.

PMID- 9011799
TI  - Case 26-1996: hypersensitivity to carbamazepine.

PMID- 9011800
TI  - Case 26-1996: hypersensitivity to carbamazepine.

PMID- 9011801
TI  - Liver disease in pregnancy.

PMID- 9011802
TI  - Liver disease in pregnancy.

PMID- 9011803
TI  - Liver disease in pregnancy.

PMID- 9011804
TI  - Theophylline and sleep-disordered breathing in heart failure.

PMID- 9011805
TI  - Gaucher cells in pulmonary-capillary blood in association with pulmonary
      hypertension.

PMID- 9011806
TI  - Urinary tract infections in young women.

PMID- 9011807
TI  - Urinary tract infections in young women.

PMID- 9011809
TI  - Physician-assisted suicide.

PMID- 9011808
TI  - Physician-operated networks and the new antitrust guidelines.

PMID- 9011811
TI  - Physician-assisted suicide.

PMID- 9011810
TI  - Physician-assisted suicide.

PMID- 9011813
TI  - Physician-assisted suicide.

PMID- 9011812
TI  - Physician-assisted suicide.

PMID- 9011814
TI  - Physician-assisted suicide.

PMID- 9011815
TI  - Physician-assisted suicide.

PMID- 9011816
TI  - Physician-assisted suicide.

PMID- 9011817
TI  - Anticoagulation for nonrheumatic atrial fibrillation.

PMID- 9011818
TI  - Cardiac-surgery performance reports.

PMID- 9011819
TI  - Cardiac-surgery performance reports.

PMID- 9011820
TI  - Quality-of-care data from managed-care organizations.

PMID- 9011821
TI  - The role of "hospitalists" in the health care system.

PMID- 9011822
TI  - The role of "hospitalists" in the health care system.

PMID- 9011823
TI  - The role of "hospitalists" in the health care system.

PMID- 9011824
TI  - The role of "hospitalists" in the health care system.

PMID- 9011825
TI  - The role of "hospitalists" in the health care system.

PMID- 9011826
TI  - The utility of mitochondrial DNA restriction analysis in the classification of
      strains of Chrysosporium (hyphomycetes).
AB  - The taxonomy of the fungal genus Chrysosporium is mainly based on morphological
      features. In our current studies we have found several Chrysosporium species
      which showed intermediate morphological characteristics between several species.
      For this reason, we have carried out an analysis of the mitochondrial DNA
      restriction fragments of these strains that have permit us to classify each
      isolate strain in a species.

PMID- 9011827
TI  - Skin and serum reactivity among humans to histoplasmin in the vicinity of a
      natural focus of Histoplasma capsulatum var. duboisii.
AB  - The epidemiology of histoplasmosis duboisii (African histoplasmosis) is not well
      understood. The present study was carried out to investigate the prevalence of
      skin sensitivity and to determine by immunodiffusion the presence of antibodies
      among humans to histoplasmin around a recently discovered natural focus of
      Histoplasma capsulatum var. duboisii in a bat cave in Ogbunike in the Anambra
      State of Nigeria. Out of the 40 subjects, all young adults aged 18-30 years,
      comprising cave guides, traders and farmers examined in the immediate vicinity of
      the cave, 14 (35.0%) gave a positive skin test. In another population of the same
      age group, comprising 620 persons, viz. traders, farmers, palm oil workers and
      some patients attending rural clinics, examined in other nearby areas in Anambra
      State, 55 (8.8%) reacted positively to histoplasmin. In the immunodiffusion
      tests, 2 (2.08%) of the 96 school children and 17 (9.4%) of the 181 young adults,
      including farmers, palm oil workers and traders tested amongst the population
      around the cave, demonstrated precipitating antibodies to histoplasmin in their
      sera. Only 5 (0.79%) of the 630 adults of the same age group with similar
      occupations examined from other areas in Anambra State had precipitating
      antibodies. Out of another 50 subjects examined, viz.; wood workers, traders,
      farmers, and school teachers in Nsukka in the Enugu State, two (4.0%)
      demonstrated antibodies. It is suggested that asymptomatic infections due to the
      duboisii variety of H. capsulatum may be common in the human population around
      the cave. A diligent search with the help of local hospitals and public health
      officials may reveal clinical cases of histoplasmosis duboisii with cutaneous and
      systemic lesions.

PMID- 9011828
TI  - Transformation of the mycotoxin ochratoxin A in plants. 2. Time course and rates
      of degradation and metabolite production in cell-suspension cultures of different
      crop plants.
AB  - Ochratoxin A, one of the most toxic mycotoxins, can be metabolized nearly
      completely by suspension cultures of various plant cells. The transformation
      products identified in this study were almost the same in the cell-suspension
      cultures of maize, carrot, tomato, potato, soybean, wheat and barley, but the
      quantitative distribution differed strongly depending on incubation time and
      species of plant-cell culture. The compounds were extracted with ethyl acetate
      and detected by reversed-phase HPLC with gradient elution. From the result it is
      supposed that besides ochratoxin A also ochratoxin derivatives may occur in food
      and feedstuff of plant origin.

PMID- 9011829
TI  - Effects of the infection of toxigenic fungi and an antagonistic Streptomyces
      strain on wheat spikes.
AB  - The objective of the present study was to determine the effect on infection of
      wheat spikes by toxigenic fungi (Aspergillus parasiticus NRRL 2999, Fusarium
      tricinctum NRRL 3299, Fusarium graminearum CEREMIC 136/92) and a strain of
      Streptomyces sp. that is antagonistic to the above-mentioned fungi. Wheat grains
      (variety GRANERO INTA) were sown in 8 pots containing natural soil and kept in a
      greenhouse chamber. In the period of the early anthesis the wheat spikes were
      inoculated with conidial suspensions of each of the fungi in the presence or
      absence of Streptomyces. Each pot was assigned a different treatment. After an
      incubation of 100 days and when the wheat plants had attained maturity, the
      spikes were separated and the following items were determined: (a) number of
      grains obtained with each treatment, (b) weight of the grains, (c) average weight
      of the grains/treatment, (d) average number and weight of the grains/spike, and
      (e) invasion of the caryopses by the microorganisms determined by the analysis of
      the caryopses in seriate histological sections. There was a significant decrease
      (p < 0.01) in the average weight of the caryopses and in the weight and number of
      grains/spike in the presence F. graminearum. The wheat grains were invaded by of
      F. graminearum and A. parasiticus, an effect which was partially attenuated by
      the presence of antagonist Streptomyces sp. Nevertheless, the effect was not
      strong enough to prevent the degenerative consequences on the size and weight of
      the grains produced by F. graminearum.

PMID- 9011830
TI  - Reflections on "pulling the plug".

PMID- 9011831
TI  - Laughing as we go. Humor and aging.

PMID- 9011832
TI  - Ring clip with laterally curved blades for carotid cave aneurysm.

PMID- 9011833
TI  - [Lipoprotein (a) and plasminogen in atherosclerosis].
AB  - The aim of this study was to evaluate plasma levels of lipoprotein (a) [LP(a)]
      and plasminogen in patients affected with atherosclerotic disease and to
      understand the mutual relationships. Eighty-four patients affected with
      atherosclerosis were examined and divided as follows: group I, 24 patients with
      peripheral arteriopathy; group II, 40 patients with ischemic heart disease
      (myocardial infarction and/or angina pectoris); group III, 20 patients with multi
      infarct dementia; group IV (control group) with 20 healthy young subjects. The
      results show that Lp(a) plasma levels, in atherosclerotic patients, are higher
      than 30 mg/dl, while the plasminogen levels are lower than 80 mg/dl. There is an
      inverse correlation between these two data. Moreover, a different behaviour of
      Lp(a) and plasminogen rate related to age of patients, to number of
      atherosclerotic lesions or to acuteness of ischemic heart disease, was observed.

PMID- 9011834
TI  - [Macro- and microcirculation study in diabetic patients].
AB  - In diabetics, vascular examination may consider great and medium arteries and
      microcirculation. The aim of this study is correlation between stenosis in
      carotid and femoral bifurcation, ultrasound biopsy, and laser-Doppler
      measurements of distal microcirculation in diabetics. During a six month period,
      we have examined 90 diabetics in the diabetological service of the Civita
      Castellana Hospital (Viterbo, Italy), asymptomatic for any vascular distal,
      cerebral or coronary disease. Subjects were 49 +/- 20 years old with 15 +/- 5
      years of diabetes; glycosilate haemoglobin was 7% (mean). 70% of diabetics (62%
      type I, 38% type II) had an altered veno-arteriolar reflex and 30% of these an
      ultrasound biopsy value of more than 25. These data demonstrate that most
      diabetic subjects develop an early, preclinical neuropathy that is directly
      proportional to the arterial wall condition.

PMID- 9011835
TI  - ["White coat effect" on blood pressure].
AB  - In the past few years non-invasive ambulatory blood pressure monitoring has
      become a widespread technology in the assessment of arterial hypertension. The
      "white coat effect" concept derives from comparison between "clinic" and
      "ambulatory" blood pressure. It consists of two opposite conditions: clinic
      hypertension with ambulatory normotension (the so-called "white coat
      hypertension") and clinic normotension with ambulatory hypertension (the so
      called "white coat normotension"). Nearly 20% of unselected referred populations
      shows conditions that may not need medical treatment, such as the "white coat
      hypertensives", or that may need antihypertensive therapy, such as the "white
      coat normotensives".

PMID- 9011836
TI  - [Tridimensional echocardiography: general principles and clinical applications
      (with special reference to congenital heart diseases)].
AB  - Methods of three-dimensional reconstruction of cardiac images and emerging
      clinical applications are described, with special reference to congenital heart
      disease. Compared to other techniques providing dynamic three-dimensional
      visualization of heart structures, echocardiography has advantages of better
      temporal resolution and minor cost. Current applications include assessment of
      volumes and global and regional ventricular performance, evaluation of time
      motion of valves and other dynamic processes together with color-flow images, and
      dissection of the heart into specific areas of interest, such as atrial septum,
      mitral inflow and aortic outflow. In complex congenital heart disease, three
      dimensional reconstruction provides an interpretation of the mode of
      atrioventricular and ventriculoarterial connections, with simulations of a
      "surgeon's view" of the heart. Defects as atrioventricular canal, double inlet
      left ventricle and tricuspid atresia can be examined in details concerning the
      architecture of valvar and subvalvar apparatus and presence and importance of
      ventricular septal defect. Other congenital malformations such as transposition
      of great arteries, truncus, coarctation syndrome, and double outlet right
      ventricle can be assessed in regard to interventricular communication and
      infundibular obstruction. Multiplane transesophageal probes are best suitable to
      this sort of electronic vivisection, but rotational and linear scanning methods
      have also given useful images of cardiac structures in children as well as
      adults. Validation studies are in progress on the reliability of a number of
      quantitative parameters that can be derived from the three-dimensional data set.

PMID- 9011837
TI  - [Analysis of the DRG rate system in cardiology. Results of a comparative study of
      diverse regions].
AB  - Following the introduction of the reimbursement system for services, the use of a
      different rate system can have a singularly negative effect on the actual
      clinical activity. A discipline such as cardiology can be particularly exposed to
      the eventual variation in rates, and we feel it is necessary to introduce
      appropriate systems of analysis to deal with this problem. In the present study
      we carried out an analysis of the rate parameters adopted in Italy, by the
      Ministry and by two Regions: Lombardia and the Marche. The study took into
      account only the DRGs of cardiological diseases. We found that regional rates
      differed greatly according to the evaluation given to some diagnostic groups,
      inevitably determining the under valuation of the clinical complexity of some
      cases with the risk of a financial squeeze of certain structures. Variations in
      the composition of rate lists can also lead to distorted behaviour when selecting
      cases on condition of the quality of services given. The comparison of rates
      between the Marche and Lombardia regions showed a great difference in the number
      of subjects hospitalised for critical pathologies and stable ones, putting the
      wards in the Marche region in potential difficulty as their activity is aimed at
      more intensive and emergency therapy. The present study aims at underlining these
      problems, identifying the most evident inconsistencies and opening a debate on
      the subject.

PMID- 9011838
TI  - [Endovascular treatment of abdominal aorta aneurysms using the Stentor device.
      Preliminary experience].
AB  - PURPOSE: The aim of this report is to describe our experience with the Stentor
      device for endovascular treatment of the abdominal aortic infrarenal aneurysms
      also extending to the bifurcation and the common iliac arteries. Stentor is a
      thermal memory (Nitinol) self-expanding graft, covered by an external 0.1 mm
      Dacron material. METHODS: Between December 1994 and July 1995 endoluminal repair
      of infrarenal aneurysmal disease was undertaken in 6 patients at high surgical
      risk. The lesions include 2 infrarenal abdominal aorto-aortic aneurysms, 2
      infrarenal abdominal aortic aneurysms extended to the common iliac arteries and 2
      false aortic aneurysms in patients with previous aorto-bifemoral graft. Straight
      grafts were implanted in 4 patients and bifurcated in 2. Repair was done in the
      operating room using general anesthesia. The endograft was placed through remote
      arteriotomies and advanced under fluoroscopic guidance to his predetermined site.
      Three-dimensionally reconstructed spiral CT scan and arteriography were performed
      before the procedure for a preoperative accurate measurement for endograft
      preprocedural adaptation in length and diameter. RESULTS: All endografts were
      successfully deployed. Intraoperative arteriography at the end of the procedure
      revealed a distal "leak" into an aneurysmal common iliac artery, due to diameter
      mismatch, in a bifurcated device. There was no instance of embolism or graft
      migration. No patient required conversion to an open operation. There were no
      instances of embolism or graft migration. No patient required conversion to an
      open operation. There were no coagulative disorders. Minor complications were:
      groin haematoma (1), fever (1), intestinal paralysis (1), pelvic pain (1). Follow
      up with spiral CT-scan and echo color-Doppler confirmed normal blood flow through
      the graft in 5 patients and persistence of distal leak in 1 patient. CONCLUSIONS:
      These preliminary results demonstrate the accuracy of implantation and device's
      adaptability to the particular anatomy of the aneurysmal aorta and iliac
      arteries. Proximal fixation to the aortic wall, secure seal at the proximal and
      distal fixation point present the critical aspects of this new surgical
      technique. More detailed preoperative measurements of aneurysmal disease are
      required rather than for traditional surgery. Presently we prefer to treat the no
      operable patients with this endovascular technique in relation with shortness of
      the follow-up.

PMID- 9011839
TI  - [Venous thromboembolism: epidemiology and risk factors].
AB  - The prevalence of DVT in the general community has been estimated from large
      descriptive studies of symptomatic patients; the annual incidence of proximal DVT
      has been reported to be 48 cases for 100,000. When associated to known risk
      factors, the incidence of DVT is strongly elevated; postoperative DVT occurs, for
      instance, in 5% to 40% of patients undergoing surgical procedures. Estimated of
      the incidence and prevalence of PE are less reliable than for DVT because the
      ante-morten diagnosis of PE is difficult and the post-mortem diagnosis highly
      selective. An analysis conducted on 11,000 autopsies showed that 316 of these had
      macroscopic pulmonary emboli; nevertheless, 11% of cases only had the diagnosis
      before death, while 32% of the patients were diagnosed as died of myocardial
      infarction, 15% of cerebrovascular disease and 14% of pneumonia. Update results,
      indicate that mortality due to PE is the first cause of death in hospitalized
      patients. Venous thromboembolism is a common disease often misdiagnosed because
      of low accuracy of clinical diagnosis; correct approaches for prophylaxis,
      therapy and to diagnosis are necessary to manage high-risk patients for DVT
      and/or PE and to reduce costs and social impact.

PMID- 9011840
TI  - [Bilateral aneurysm of the popliteal vein. A case report and review of the
      literature].
AB  - We report a case of a 86-year-old woman, with a 1-year history of pain during
      walking and standing; a duplex scanning of the popliteal fossa was performed
      bilaterally. We pointed out the presence of a bilateral popliteal vein aneurysm,
      partially thrombosed. She was treated only with oral anticoaugulant therapy,
      because of her age. Venous aneurysms are quite rare and are considered to be true
      when all three cell layers are present in the vessel wall; bilateral popliteal
      venous aneurysm is very rare and only one case was previously described. This
      report describes, moreover, with a large review of the world literature,
      histologic features and diagnostics and therapeutic choices.

PMID- 9011841
TI  - [Neuropathy of the common peroneal nerve caused by giant cell arteritis].
AB  - Mononeuritis multiplex involving median or common peroneal nerves, presumed to be
      caused by arteritis of the vasa nervorum, is a relatively rare complication of
      giant cell arteritis. We present two cases of popliteal neuritis complicating
      temporal arteritis during corticosteroid treatment.

PMID- 9011842
TI  - Role of nitric oxide and superoxide balance in hypoxia-reoxygenation proximal
      tubular injury.

PMID- 9011843
TI  - [An epicritical review on the pathology of angiodysplasias].

PMID- 9011844
TI  - [Who needs a gastroenterology pathologist?].

PMID- 9011845
TI  - [A case of pulmonary schwannoma].
AB  - Intrapulmonary neurogenic tumors are extremely rare. The first observation was
      reported by Rubin and Aronson in 1940, subsequently 40 cases were identified.
      Even if this tumor has a neurogenic origin it does not often have symptoms and to
      get diagnosis it's necessary surgical excission and histological study. Because
      of identification and differential diagnosis often of the tumor is very important
      for patient's prognosis, the authors present a case that they have observed.

PMID- 9011847
TI  - Marijuana.

PMID- 9011846
TI  - Fatigue of resin-bonded amalgam restorations.
AB  - Standardized MOD cavities were prepared in 80 human premolars, which were treated
      with either adhesive resin or copal varnish and then restored with amalgam.
      Fracture resistance of these groups was compared after 24 hours of storage, 4
      weeks of storage with thermocycling, and after 500 days of storage. The buccal
      cusps were loaded at an angle of 30 degrees to the tooth long axis until fracture
      occurred. Additionally, survival curves were compared for adhesive resin and
      copal varnish groups that had been repeatedly load cycled until fracture
      occurred. The 24-hour adhesive resin group was significantly stronger than the
      corresponding copal varnish group (P < 0.05). However, no significant differences
      between adhesive resin and copal varnish were found for the other thermocycling,
      extended 500-day storage, or load cycling tests. In conclusion, the strengthening
      effect of an adhesive resin on teeth restored with MOD amalgam restorations was
      transient.

PMID- 9011848
TI  - [Contributions of pediatric and adolescent psychiatric and development
      psychological research on objective definition of the child welfare concept].
AB  - The term of "child well-being" is a rather vague notion in the German
      jurisdiction and has to be reinterpreted according to each single case. The
      present article describes the historical context and different attempts to come
      to a more concrete definition of the term suitable to serve as a guideline for
      expert opinion and jurisdiction. The authors discuss the question in which way
      scientific findings may enhance an objectivation of "child well-being", stressing
      especially contributions coming from the fields of developmental psychopathology,
      attachment research, interaction and family research and research on risk factors
      and protective factors.

PMID- 9011849
TI  - [Official approach to sexual abuse].
AB  - The topic of sexual abuse must be seen from different points of view as the State
      presents itself at three levels: legislative executive, and judicial. The
      executive power is mainly represented by the Jugendamt (Youth Office) whose tasks
      are set out precisely in the Kinder- und Jugendhilfegesetz (KJHG) (Child
      Protection Act); however, the Act itself does not state clearly how the
      responsibilities should be fulfilled. Even so, cooperation between non-government
      organizations, the Family Court and other cited institutions (i.e. school,
      police) is necessary. In addition, the staff members of the Youth Office should
      be experts (i.e. adequate education, advanced training, supervision) but often
      lack the necessary knowledge of law, developmental psychology and paediatric
      psychiatry. The necessary skills such as interviewing methods, class- and age
      specific language and professional recording are not always available and the
      plans for the child's care prescibed by the Act are often inadequate. The data
      protection regulations play a counterproductive role and financial shortages are
      often born by the weakest members of the society. The judicial power in the
      Family Court area has to free itself from possible procedures of the Criminal
      Court and has to intervene earlier. A legal representation of the child should be
      made available as soon as possible. The family judges should exhaust all legal
      possibilities. Police and public prosecution should cooperate better with Youth
      Protection and Family Courts. Judges should be more willing to believe child
      witnesses. All the possibilities of the Code of Criminal Procedure should be used
      in favour of the child. The compensation for victims of sexual abuse should be
      more directly aimed towards helping the victims. The legislative power could
      break up a narrow jurisdiction (continuation of offence, definition of violence,
      verification of credibility). It could apply new methods (video-recording to
      replace public examination, psychotherapeutic treatment instead of, or combined
      with penal sentence sanctions) and correct inadequate acts (competence of Family
      Court and Guardianship Court, counterproductive data protection). In conclusion,
      it must be said that many details concerning the official approach to sexual
      abuse could be improved. However, the main problem lies in the fact that the
      State does not really attempt to create a systematic solution to sexual abuse.
      The ad hoc reaction in Germany has led to an uncoordinated set of rules and
      practices without a common sense of purpose.

PMID- 9011850
TI  - [Family tension during suspected abuse situations].
AB  - In cases of mere suspicion, interference with the civil rights of the suspect or
      of another person are justified only for the purpose of clarifying the suspicion.
      Interference intended to climinate the alleged threat are prohibited. In order to
      establish facts without a hearing, a medical and psychological examination of the
      child in question needs to be considered. Separation of the child from its
      family, or interruption or even termination of contact with the person having
      custody of the young children is generally forbidden during the period of
      investigation. If the child definitely refuses contact with the suspect while the
      facts are being investigated, a supervised right to access to the child is the
      least intrusive intervention that can be considered. The supervised right of
      access is adequate if it is limited to the time necessary to establish the facts.
      Intervention by the court during the period of investigation is allowed only
      within the limits indirectly inferred in the civil rights provided in Article 6.
      The court must consider the interests of the entire family, particularly the well
      being of the other underage children who are members of that family.

PMID- 9011852
TI  - [Stress experiences of children in criminal proceedings].

PMID- 9011851
TI  - [Between family-oriented help and child protection--interventions within the
      scope of the child and youth aid law: an unsolvable dilemma?].
AB  - The new child care and protection legislation (German Social Aid) emphasises the
      support of the parents' responsibility for education. In addition, it includes
      separate provisions and opportunities for counseling and supporting young
      children and adolescents in crisis situations. Finally, it requires the Youth
      Welfare Office to inform the Guardianship Court if a legal decision is required
      to avert a threat of the child's welfare. In the process of making the complex
      precise and responsible decision on the prognosis for the child, the experts from
      the Youth Welfare Office mus decide weather to respond to a threat to the child
      with family-oriented support, of with intervention concerning parental care that
      will usually lead to the separation of the child from its social setting.

PMID- 9011853
TI  - [Institutional management of child sexual abuse].
AB  - In the years 1992-94 the Child Protection Centre Kiel carried out the first
      investigation of how various institutions (nursery schools, schools, advisory
      offices, children's specialists, youth welfare departments, police, judicial
      authorities etc.) in the German-speaking area deal with suspected cases of sexual
      child abuse. A special comprehensive questionnaire and a personal interview were
      drawn up to find out details concerning knowledge, experiences, attitudes and
      concrete measures of the employees. The particulars were evaluated of about 900
      persons from three differently structured districts in Schleswig-Holstein. The
      institutions (with the exception of the police and judicial authorities) do not
      have any clear concepts regarding the handling of suspected cases of sexual child
      abuse. The reactions of the institutions usually depend on the level of
      knowledge, experience and subjective assessment of individual employees. Roles
      are not clearly defined and there is not enough cooperation between the
      institutions. The employees require more practice-orientated training and case
      specific supervision. There are not enough coordination bodies for those
      concerned, therapeutic places and accommodation possibilities for children and
      youths as well as effective offers of assistance for adults and youths who have
      abused children.

PMID- 9011854
TI  - [2 steps forward and one back?--Response of child welfare to sexual abuse
      experiences of girls and boys].
AB  - What has been changed in the system of social help since sexual abuse became a
      public topic? Is social work capable of providing adequate help and support for
      the survivors? The article presents the results of a three-year-lasting research
      project. In three different regions the authors have scrutinized 1. the
      institutions offering help, 2. the knowledge of and the attitude towards sexual
      violence of the professionals and 3. the conceptional assumptions leading social
      work. The results show that the situation for survivors of sexual abuse has
      definitely improved, because there are more helping institutions and the
      professional awareness has increased. But for a profound reorganization of help,
      restrictive financial politics, internalized prejudices and institutional
      concepts need to be changed.

PMID- 9011855
TI  - [Institutional handling of criminal measures in sexual abuse. Results of a survey
      of experts].
AB  - A broad spectrum of very different institutions is confronted with the problem of
      sexual child abuse. So far, only a few systematic descriptions of institutional
      interventions and their impact on sexually abused children exist. In this
      article, first results are presented of a study investigating "individual and
      institutional reactions on sexual child abuse'. In dealing with this problem
      legal provisions are of special importance. The results presented are based on
      data obtained from questionnaires and qualitative interviews with experts (median
      of vocation experience: 8 years) in two german cities (berlin/cologne).
      Questionnaires were filled in by 195 experts from the entire institutional
      spectrum (counselors, clinical centres, youth welfare departments, public
      prosecutors, courts of justice, police), of whom 40 additionally took part in a
      detailed interview. This article focuses on the question, how different
      institutions handle legal provisions. The use of criminal law exemplarily shows
      the different impact of legal provisions on the interventions of counselors. The
      close connection between the assessment of legal interventions and counseling
      concepts could be shown at the example of the allegedly homogeneous group of
      specific counselors.

PMID- 9011856
TI  - [Kinetics of serum albumin adsorption on the macroporous glass MPS-250 GKH].
AB  - Intrinsic diffusion (defined as diffusion within micropores or microgranules) was
      shown to be a major factor that determines the kinetics of bovine serum albumin
      adsorption to macroporous silica MPS-250 GKh. The effective coefficient of
      intrinsic diffusion (within the silica phase) was calculated (Def = 7 x 10(-7)
      cm2/s).

PMID- 9011857
TI  - [Isolation of bacterial endotoxins from Pseudomonas putida 36 and Escherichia
      coli (vulgaris)].
AB  - Extracts of endotoxins from Gram-negative bacteria Pseudomonas putida 36 and
      Escherichia coli (vulgaris) grown upon solid-phase or submerged cultivations were
      studied. The composition of the extracts was analyzed by gel-filtration. Ps.
      putida 36 was shown to be a promising producer of bacterial endotoxins.

PMID- 9011858
TI  - [Preparation and characteristics of immobilized collagenase isolated from crab
      Paralithodes camtschatica].
AB  - Collagenolytic protease from hepatopancreas of king crab was immobilized on water
      soluble reactive polymers containing N-succinimide units and possessing different
      hydrophobicity-hydrophilicity balance. The immobilized enzyme displayed higher
      heat stability, but its proteolytic activity decreased with the increase in the
      number of the copolymer hydrophobic groups. Highly active thermostable
      preparations of collagenolytic protease were obtained by copolymerization. The
      copolymerization did not affect the enzyme activity and increased the protease
      heat stability to the formation of pseudocross-links of protein molecules in
      their associates.

PMID- 9011859
TI  - [Isolation and physico-chemical characteristics of Staphylococcus hyaluronidase].
AB  - A scheme for purification of hyaluronidase from Staphylococcus aureus 0-15 that
      allows to produce a 550-fold-purified preparation with a high specific activity
      was developed. Hyaluronidase was found to consist of two molecular forms with
      different molecular weights. Staphylococcus hyaluronidase referred to as a
      complex preparation and its molecular forms have action optimum at pH 5.0-7.2 and
      at a temperature between 30 and 37 degrees C. The enzymes were highly specific to
      their substrate: they catalyzed the depolimerization of hyaluronic acid but did
      not split the other glycosaminoglycans.

PMID- 9011860
TI  - [Influence of Bacillus intermedius RNAse on growth-stimulating and antagonistic
      characteristics of Trichoderma harzianum].
AB  - Bacillus intermedius RNAase (with specific activity of 1,000,000 units per one mg
      of protein) at concentration of 1 x 10(-3) mg/ml was shown to increase
      antagonistic and growth-stimulating properties of Trichoderma harzianum. An
      application of trichodermin which was treated with an enzyme enhanced cucumber
      crop capacity by 15-18% in industrial conditions.

PMID- 9011861
TI  - [Immobilization of enzymes on carriers with magnetic properties: the search for
      optimum conditions for immobilization of alkaline phosphatase from the chicken
      gut].
AB  - Chicken intestine alkaline phosphatase was immobilized on seven carriers by
      adsorption or covalent binding. The efficiency of immobilization depended on the
      carrier, immobilization method, and initial enzyme concentration. The heat
      stability of the soluble and immobilized enzyme preparations, and the dependence
      of the enzyme activity on pH and Zn2+ and Mg2+ ions were studied. Alkaline
      phosphatase immobilized on magnetic carriers displayed lower heat stability than
      the soluble enzyme. The temperature optima of the immobilized and soluble enzymes
      were 80 and 60 degrees C; the pH optima were 9.0 and 8.0, respectively. Ions Mg2+
      and Zn2+ were found to play an important role in the activation of both soluble
      and immobilized enzymes and their stabilization at high temperatures.

PMID- 9011862
TI  - [Preparation of fiber materials containing both the immobilized proteolytic
      enzyme and antimicrobial substance, and study of their properties].
AB  - Properties of joint immobilization of a proteolytic enzyme (terrilytin, trypsin,
      collytin, or protease C) and an anti-microbe compound to cellulose copolymer
      containing carboxyl groups were investigated. It was established that the
      molecule of anti-microbe substance containing a few base groups enhanced
      stability of the enzyme immobilized, most likely due to additional fixation of
      the enzyme macromolecule. Changes in activity of the materials containing both
      protease and anti-microbe compound were studied upon gamma-sterilization and
      subsequent prolonged storage. The materials with combined biological action were
      demonstrated to accelerate markedly wound cleansing and healing.

PMID- 9011863
TI  - [The effect of electromagnetic field on the biosynthesis and various properties
      of extracellular proteinase and lectin from Bacillus subtilis 316 M].
AB  - The promoting effect of electromagnetic field (EMF) on biosynthesis and activity
      of extracellular proteinase and lectin in B. subtilis 316 M was observed. It
      caused 1.5- and 4-fold increase of the metabolites yield respectively. The EMF
      stimulated a 2-fold activation of lectin, rise of the enzyme activity and a shift
      of it pI from 11.4-11.5 to 9.2-9.3.

PMID- 9011864
TI  - [Complex-formation of phospholipase A2 with fragments of nucleic acids and
      approaches to its elimination].
AB  - Formation of phospholipase A2 stable complexes with nucleic acid fragments was
      observed upon the isolation of the enzyme from pig pancreas. This complex could
      be disrupted by neither DNA precipitation with protamine chloride and
      cetyltrimethylammonium bromide nor chromatography on DEAE-cellulose and CM
      cellulose or hydroxyapatite. The treatment of the complexes with 1 M acetic acid
      followed by gel-chromatography on Sephadex G-75 in 1 M acetic acid resulted in
      complete separation of active phospholipase A2 from DNA fragments.

PMID- 9011865
TI  - [Radiation-protective effect of S-methylmethionine (vitamin U)].
AB  - S-Methylmethionine had moderate radioprotective activity, the efficiency of
      radioprotection was 15-30%, the value of dose decrease coefficient-1.2.
      Biological effect of S-methylmethionine was probably provided by its ability to
      decrease the level of lipid peroxidation and inhibit monoamine oxidase activity.

PMID- 9011866
TI  - [The use of electro-optic method for control of biological preparations].

PMID- 9011867
TI  - [Pathogenetic significance of IgE-binding epitopes allergens].

PMID- 9011868
TI  - [Serologic and skin test diagnosis of birch pollen allergy with recombinant Bet v
      1, the chief allergen of birch].
AB  - BACKGROUND: Type I allergy represents a severe health problem in industrialized
      countries where up to 20% of the population suffers from allergic rhinitis,
      conjunctivitis and allergic asthma bronchiale and in severe cases from
      anaphylaxis, leading to death. OBJECTIVE: The aim of this study was to evaluate
      recombinant Bet v 1, the major birch pollen allergen for in vivo and in vitro
      diagnosis of birch pollen allergy. METHODS: A group of 51 birch pollen allergic
      patients and eight non-allergic control individuals were tested for birch pollen
      allergy by skin-prick and intradermal testing, comparing commercial birch pollen
      extracts with recombinant Bet v 1. Quantitative and qualitative serological
      testing was done with natural and recombinant allergens by radioallergosorbent
      test (RAST), enzyme-linked immunosorbent assay (ELISA) and immunoblotting.
      RESULTS: Recombinant Bet v 1 allowed accurate in vivo and in vitro diagnosis of
      tree pollen allergy in 49/51 patients tested. No false positive results were
      obtained in any in vitro assay system (ELISA, Westernblot) or by skin testing
      (skin-prick, intradermal test) with recombinant Bet v 1. CONCLUSION: Our results
      document that recombinant Bet v 1 produced in bacterial expression systems allows
      accurate in vitro and in vivo diagnosis of birch pollen allergy in > 95% of birch
      pollen allergic patients.

PMID- 9011869
TI  - [Information on the new 4111 occupational disease: "chronic obstructive
      bronchitis or emphysema in miners of bituminous coal mines with evidence of the
      exposure to a cumulative fine dust dose around 100 ([mg/m3] x years)].

PMID- 9011870
TI  - [New therapy concepts in fibrosing lung diseases].

PMID- 9011871
TI  - [Computer graphics methods for 3-dimensional imaging of intrapulmonary space
      occupying lesions of CT and MRI images].
AB  - AIM: To improve the pre-operative planning of interventional procedures in thorax
      surgery different methods of computer-graphical visualization of intrapulmonary
      lesions and adjacent anatomical structures based on CT and MR data were realized
      and compared to each other. DESIGN: In 21 patients with intrapulmonary lesions
      the image data was segmented by interactive and automatic algorithms and
      different reconstruction techniques were applied (maximum intensity projection;
      color-encoded and transparent surfaces; volume rendering). Based on these three
      dimensional reconstructions, different views from arbitrary perspectives
      (including simulated endoscopic images) were generated and animated film
      sequences of the 3D scene were displayed with 30 frames/second. RESULTS: For all
      patients under review, a high-quality presentation of the relevant structures was
      obtained by use of the applied computer-graphical techniques. Even combinations
      of different visualization methods in one image can be generated with the
      software we developed. CONCLUSIONS: The various methods for image segmentation
      allow a fast and comfortable processing even of large data sets. The calculated
      values of tumor surface and volume can be used for quantitative studies and
      therapy control. The planning of surgical and interventional procedures can be
      supported by the simultaneous visualization of the intrathoracic lesion and the
      surrounding structures.

PMID- 9011873
TI  - [Modulation of drug penetration in the skin].
AB  - Drugs administered topically on skin should act either dermally or transdermally.
      They have to cross the stratum corneum (SC) which is responsible for the barrier
      function of the skin. Most of the drugs are not able to penetrate the SC. For
      this kind of drugs it is necessary to search for penetration enhancers to
      increase drug absorption. Sometimes systemic side effects caused by drugs applied
      topically have to be reduced or prevented. In these cases, so called retarders or
      reducers are applied as penetration modulators. Penetration into and through the
      SC may be influenced by physical means (hydration, iontophoresis, phonophoresis,
      temperature) or chemical substances. Alcohols, sulphoxides, fatty acids, esters,
      Azone, pyrrolidones, urea and polyoles are applied as penetration enhancers. The
      objectives for the use of a penetration modulator are to change the solubility
      and diffusivity of the drug in the SC reversibly. It is necessary to distinguish
      between modulators which influence the lipid pathway and those which are able to
      modify diffusion via the polar pathway.

PMID- 9011872
TI  - [Progressive course of idiopathic pulmonary fibrosis in 2 monozygotic twin
      sisters].
AB  - This is the report on a lethal course of idiopathic pulmonary fibrosis in two
      monozygotic twins. The specific aspects of familial idiopathic pulmonary fibrosis
      and the pattern of inheritance are discussed. The pattern is probably autosomal
      dominant with variable penetrance.

PMID- 9011875
TI  - Of art and articles.

PMID- 9011874
TI  - Standards of practice for physical therapy and the accompanying criteria. The
      American Physical Therapy Association.

PMID- 9011876
TI  - 1995 in the rearview mirror.

PMID- 9011877
TI  - [Outbreak of oropouche virus fever in Serra Pelada, municipality of Curionopolis,
      Para, 1994].
AB  - In the final of November 1994, an outbreak of a febrile disease was observed in
      the Serra Pelada gold mine (5 degrees 35'S: 49 degrees 30'W) in the Southeast
      region of Para State. Twenty samples were collected and sent to the laboratory of
      Arbovirus of Instituto Evandro Chagas. The tests showed that the disease was
      caused by Oropouche virus (Bunyaviridae, Bunyavirus, Simbu serological group).
      Between 8-22 December 296 serum samples were taken (54 from febrile patients, 16
      paired samples and 242 from contacts and convalescent patients) of the 73
      familiar groups. From febrile patients, ten Oropouche virus strains were
      obtained. From paired serum, six seroconversions were obtained and 242 other
      Oropouche infections were diagnosed by HI and MAC ELISA. The clinical-picture of
      febrile disease accompanied by severe bedache, chills, myalgia, photophobia
      retrobulbar pain and malaise was observed. Involvement of central nervous system
      was not observed. Based on the serological data, we estimated that in the
      outbreak of Serra Pelada around 5,000 cases occurred corresponding to a
      prevalence of 83%.

PMID- 9011878
TI  - [Description of the colonization of Aedes albopictus (Diptera: culicidae) in the
      region of Sao Jose do Rio Preto, SP, 1991-1994].
AB  - This study aims to describe and analyze the colonization of Aedes albopictus
      whose presence was detected in 1991 in the area of Sao Jose do Rio. Preto already
      colonized by the Aedes aegypti. Year and month of occurrence, counties,
      composition and location of larval samples, kinds of containers, average number
      of larvae an Breteau Index bare been analyzed from the information obtained in
      measurements of larval density by Superintendencia de Controle de Endemias
      (SUCEN). The presence of Aedes albopictus was ascertained in 34 towns up to
      December 1994. The colonization of the area by the mosquito is still reduced
      showing some differences in relation to Aedes aegypti such as greater ratio
      outdoors, occupying container in different proportions. The average number of
      Aedes albopictus larvae has had influence of larvae of another species. It has
      showed a seasonal behavior similar to Aedes aegypti and it has moved from east to
      west direction.

PMID- 9011879
TI  - [Domestic infestation by Triatoma infestans and prevalence of Trypanosoma cruzi
      seropositives in a rural area of the Argentinian northeast].
AB  - An epidemiological study was carried out from April 1991 to December 1993 to
      obtain a general view of T. cruzi domestic transmission in rural areas of San
      Miguei Department, Corrientes. From 100 analyzed households, 50.0% was infested
      by T infestans (Klug, 1834) and 1.0% by T. sordida (Stal, 1859). Domiciliary
      colonization by T. sordida is reported for first time in Corrientes province. T.
      cruzi infection of T. infestans was 23.1%. Indirect hemagglutination and indirect
      immunofluorescence antibody tests were used for detection of anti T. cruzi
      antibodies in 388 human sera, 23.4% showed serological reactivity. An important
      high rate (12.9%) was observed in the age group of higher transmission risk.
      Seropositives percentages increased with age and reached 50.0% in 31-40 years old
      group. Domestic infestation by T. infestans, seropositive human prevalence to T.
      cruzi and householders precarious life conditions prove that this endemic disease
      is still a problem in the studied area.

PMID- 9011880
TI  - [Open therapeutic study with aminosidine sulfate in mucosal leishmaniasis caused
      by Leishmania (Viannia) braziliensis].
AB  - From September to November 1994. 21 patients with active mucosal leishmaniasis
      were treated with aminosidine sulphate 16 mg/kg/day by intramuscular injection
      for 20 days. They were principally adult male agricultural workers. Thirteen
      patients had not received specific treatment and eight had failed to respond to
      Glucantime therapy. Diagnosis was based on clinical and epidemiological
      observations, a search for the parasite, leishmanin skin sensitivity and indirect
      fluorescent antibody serological tests. Sixty seven percent of patients had
      leishmania parasites isolated from inoculated hamsters or visualized in imprints
      or histopathological sections. The mean follow-up period was 12.6 months. All
      patients completed treatment. Side effects were pain at the injection site (86%);
      mild proteinuria (24%), elevated serum creatinine (.5%) and subclinical bearing
      loss in one of two patients who did audiometric tests. Clinical cure was achieved
      in 48% and the accumulated relapse rate was 29% (4/14).

PMID- 9011881
TI  - [The pupil in the chronic phase of Chagas disease and the reaction to pilocarpine
      and phenylephrine].
AB  - To develop a method to analyse pupillary disturbances in patients with chronic
      Chagas disease in an endemic area, ten chagasic and ten normal subjects were
      matched according to sex, age and race. Pupillary diameter and area were
      determined using projection and topography techniques and compared between
      groups. Both pupils were visualised simultaneously. In each case three
      photographs were taken under standardised illumination. The first photo was
      obtained without medication, the second, 30 minutes after instillation of 0,1%
      pilocarpine and the last 30 minutes after instillation of 3% phenylephrine (60
      minutes after pilocarpine). Pupils of chagasic patients had a statistically
      significant greater initial diameter and area, irregularity of the pupil border,
      greater percentual reduction in diameter and area after pilocarpine 0.1% and
      greater percentual increase in diameter and area after 3% phenylephrine eyedrops.
      The method developed for this study was considered satisfactory. The results
      suggest ocular autonomic nervous system disturbances in chagasic patients.

PMID- 9011882
TI  - [Prevalence of renal infarcts in autopsies of chronic Chagas disease patients].
AB  - Renal infarction (RI) is usually secondary to arterial obstruction due to emboli
      originating from the heart. Chronic chagasic patients may present cardiac
      alterations originating from intracavitary thrombi, even without congestive heart
      failure (CHF). In this study RI incidence was comparatively evaluated in chronic
      chagasic individuals, in different anatomoclinic forms and in non chagasic
      individuals. There has been a review on necropsy reports of individuals aged 20
      or over. In 259 necropsies, 78 (30.1%) were chagasics, and 19 of them (24.4%)
      developed RI, while 27 (15.0%) of the non chagasic individuals presented RI. The
      ages of chagasics with RI were similar to those of non chagasic individuals. A
      significant prevalence of RI and thrombosis among chronic chagasic individuals
      has been found. A significantly higher prevalence of RI among chronic chagasics
      having CHF (52.6%) was observed when they were compared to other forms of chronic
      Chagas disease and when compared to non chagasic individuals. It was concluded
      that RI was more frequent in chronic chagasic individuals, specially those who
      developed CHF, which probably played a role in the renal manifestations and
      systemic hemodynamic changes in those patients.

PMID- 9011883
TI  - [Oocysts of Cryptosporidium sp in feces: comparison of the modified Kinyoun and
      Heine methods].
AB  - The diagnosis of intestinal infection by Cryptosporidium sp is crucial today;
      with the progression of the AIDS epidemic, many cases of cryptosporidiosis have
      appeared in this setting and in other immunodeficiency diseases. We compared the
      advantages and disadvantages of Heine's method and modified Kinyoun's method in
      the following parameters: morphology of the parasite, quantitation of cysts,
      stability of the staining characteristics timewise on the slides and time spend
      at staining. All positive fecal smears were obtained from patients with AIDS. The
      sensitivity of these two techniques was the same. The choice should be made by
      the best aspects of each method. Heine's was better for quantitation of the cysts
      and was faster. Kinyoun's was better for conserving the stained smear.

PMID- 9011884
TI  - [Immunogenicity of the avirulent strain RV194-2 of the rabies virus in mice].
AB  - RV194-2 rabies virus, an avirulent mutant of CVS strain, induces an inapparent
      infection limited to the central nervous system (CNS) in adult mice inoculated
      intracerebrally. This fact suggest that immune response of the host is able to
      eliminate the virus in CNS. For this reason, we have studied the induction of
      interferon and the humoral immune responses in BALB/c mice after RV194-2
      inoculation. These mice presented high levels of interferon in the plasma and in
      the brain, with elevated levels of neutralizing antirabies antibodies. The 2-5A
      synthetase, an enzyme marker of interferon action, was analyzed in the brain of
      inoculated animals. Its enhancement in parallel to the interferon production in
      the brain, showed biochemical evidence that this interferon is active. Forty five
      days after RV194-2 virus inoculation, mice were protected against a challenge
      with the CVS virulent strain. The results presented herein show that RV194-2
      strain has a high level of immunogenicity.

PMID- 9011885
TI  - [Giardiasis and cryptosporidiosis in day-care centers in the municipality
      Campinas SP].
AB  - The prevalence of the Giardia duodenalis and Cryptosporidium parvum infections
      were studied in children 2-60 months old (n = 310) grouped to sex and age,
      enrolled in 8 day-care centers. Giardiasis was found in 42 (13.5%) of the
      children and, was most frequent in the age group corresponding to 19-24 months
      old although children at the first six months of life also presented positive
      faecal samples. Statistical analysis indicated no association between sex (p >
      0.05) and prevalence for Giardia infection. C. parvum was detected in 20 (6.4%)
      of the children. Children seven to twelve months old showed the greatest
      prevalence of this parasite. There were not oocysts in the stools from the
      children 25-30 months and from those older than 36 months. Oocytes were detected
      in 4 children from the 0-6 months old group. There was no significative
      difference on sex (p = 0.09) and day-care-facility (p = 0.068) for C. parvum
      infection while age was associated with infection (p = 0.004). Epidemiological
      aspects were studied by familiar inquiry, by parasitological examinations of
      stools from the contact-members of each case and from animals present at the
      residence. Prevalence for C. parvum was higher when at least one of the parents
      was a professional in the Human Health Centers (73.6% positives), when there was
      report of concomitant disease (52.6% positives) and when diarrhoea was the main
      symptom at the collection of the faecal specimens (78.9% positives). Faecal
      examinations of the domestic animals were negatives for these two parasites.

PMID- 9011886
TI  - [Measurement of the volume of the skin ulcer in cutaneous leishmaniasis].
AB  - Skin ulcers by Leishmania (Viannia) braziliensis are often deep and irregular and
      are difficult to measure by just the skin surface transverse and longitudinal
      diameters. The proposal is to mould the cavity, after local asepsis with fresh
      water plus soap, with a gelatinous plastic which contains silence, potassium
      alginate, calcium sulphate, magnesium oxide commercialized under the name of
      jeltrate (Dentsply Laboratory), by solving 9.5g of jeltrate in 20ml of fresh
      water and applying the gel on the ulcer which solidifies in 5 minutes. This mould
      is then filled with a self polymerising acrylic and its volume measured either by
      weight (by using an analytical balance)-technique 1-or by water displacement by
      applying Archimeds'principle-technique 2. We show data in a field trial before
      and after 20 days treatment in 20 patients using three different schedules as
      follows: 7 received pentamidine isethionate, 7 patients received aminosidine
      sulphate and 6 received meglumine antimoniate. The results point out that there
      was a uniform reduction of ulcer volume occurred during this period in the three
      groups, in both technique. Regarding the therapeutic schedules we are sure that
      there was a significant statistical difference between the three schedules using
      the T Student Test, which showed that aminostdine sulphate produced a better
      volume reduction of the ulcer than the other drugs. Serial moulds reflect
      clinical billing and are a permanent record. We conclude that the measure of the
      volume of the skin ulceration can be useful in the therapeutic evaluation, as a
      practical and cheap procedure, and may be used in field trials.

PMID- 9011887
TI  - [Psoriasis in HIV positive patients].
AB  - Two patients with the acquired immunodeficiency syndrome (AIDS) developed
      psoriasis, one of them presenting the more severe form and the other one the
      milder form of the disease, were treated with zidovudine per oral via, 200mg 3
      times a day. In the first case the therapeutical response was complete. No lesion
      was verified in the patient after 9 months under maintenance schedule. In the
      second case, despite the response being clear, after 6 months of treatment, the
      patient still presented furfuraceous scalings at limbs ever under the medication
      schedule.

PMID- 9011888
TI  - [Lupus erythematosus systemic and persistent pulmonary salmonellosis].
AB  - A 40-years-old woman with systemic lupus erythematosus and severe pulmonary
      nontyphoid salmonellosis (Salmonella Typhimurium), is reported. In addition the
      patient had incomplete septal cirrhosis. The authors pointed out a possible
      influence of Salmonella infection in the development of immune complex diseases.

PMID- 9011889
TI  - [History of lymphatic filariasis in Pernambuco. I. Epidemiologic and control
      aspects].
AB  - This paper is a review of lymphatic bancroftian filariasis in the State of
      Pernambuco. Brazil. It shows that reports have existed since the 1st decade of
      the century. Knowledge of the disease in several areas during different periods
      makes a retrospective analyses very interesting, particularly in Great Recife. It
      is in the city that the epidemiological and control aspects of the diseases are
      examinations in details.

PMID- 9011890
TI  - [Trials for the use of gamma rays in the prevention of Trypanosoma cruzi
      transfusion infection].

PMID- 9011891
TI  - [Occurrence of false positives in tests with synthetic peptides for the analysis
      of antibodies against the human immunodeficiency virus type 2 (HIV-2) in
      Brazilian patients infected with the human immunodeficiency virus type 1 (HIV
      1)].

PMID- 9011892
TI  - Intradermic survey with histoplasmin and paracoccidioidin.

PMID- 9011893
TI  - [Chagas disease].

PMID- 9011894
TI  - [Anesthesia history, historiology, and historiography in Spain].

PMID- 9011895
TI  - [Activity of ondansetron on the systemic vascular resistance and venous
      capacitance during cardiopulmonary bypass].
AB  - OBJECTIVE: To study the effect of ondansetron administered during cardio
      pulmonary bypass surgery, in terms of mean arterial pressure, systemic vascular
      resistance and venous system capacitance. PATIENTS AND METHOD: Twenty patients
      scheduled for non coronary cardiac surgery were randomly assigned to 2 groups.
      The study group received 4 mg ondansetron during the bypass and the control group
      received the same volume of physiological saline solution. The following
      parameters were recorded during the 10 minutes following administration of either
      substance: mean arterial pressure, calculated systemic vascular resistance, and
      the venous reservoir volume at the beginning and end of the study period.
      RESULTS: Increased mean arterial pressure and systemic vascular resistance were
      recorded in both groups from the time of injection, with the highest levels
      recorded at 10 minutes. There were no statistical differences between the 2
      groups. No changes in venous system capacitance were observed in either group, as
      there were no significant changes in venous reservoir volume of the
      extracorporeal circulation pump. CONCLUSIONS: Ondansetron at the dose used has no
      effect on arterial or venous vessels. The increased resistance recorded in both
      groups can be attributed to the release of catecholamines during non pulsatile
      extracorporeal circulation with a non pulsatile flow.

PMID- 9011896
TI  - [Comparative study of recovery from general anesthesia with halothane or
      sevoflurane in pediatrics].
AB  - OBJECTIVES: To assess the clinical signs of awakening and recovery from
      anesthesia with sevoflurane and 60% nitrous oxide in comparison with halothane
      and nitrous oxide administered to children. PATIENTS AND METHOD: A prospective
      study in 39 pediatric ASA I-II patients under 10 years of age scheduled for
      infraumbilical or otolaryngological surgery. The patients were randomly assigned
      to 2 groups to receive sevoflurane (n = 20) or halothane (n = 19). All the
      children received nasal doses of 0.2 mg/kg-1 midazolam before surgery. Induction
      was achieved by inhalation of a mixture of 40% oxygen and 60% nitrous oxide by
      face mask along with increasing concentrations of sevoflurane or halothane.
      Maintenance was with halogenated anesthetic at 1 MAC and 60% nitrous oxide-oxygen
      along with nerve blockade in the infraumbilical procedures or intravenous
      analgesia in the otolaryngological operations. We recorded time until awakening,
      orientation, score on the Aldrete scale and adverse effects during the recovery
      period. RESULTS: The children who received sevoflurane awoke and were well
      oriented earlier than were those in the halothane group (10.7 +/- 5.8 versus 18.7
      +/- 9.8 min until awakening and 15.4 +/- 8.6 versus 22.1 +/- 10 min for
      orientation); likewise the sevoflurane group children received higher scores on
      Aldrete's scale earlier than did those in the halothane group. There were no
      statistical differences between the 2 groups with respect to side effects during
      the period of awakening and recovery. CONCLUSIONS: Awakening and recovery are
      significantly faster with sevoflurane than with halothane, while the incidence of
      side effects are similar with the 2 agents.

PMID- 9011897
TI  - [Post-reperfusion syndrome in orthotopic liver transplantation].
AB  - Post-reperfusion syndrome is the most common hemodynamic pattern in liver
      transplantation, manifesting mainly through decreased heart rate, mean arterial
      pressure and systemic vascular resistances. Five factors have been implicated in
      its genesis: the heart, the circulatory system, the metabolism, reflexes and
      surgery. Ventricular function, both right and left, has been shown to be normal
      during reperfusion, in which case the visceral and, especially, liver dilation
      that occurs would be the main cause of arterial hypotension. Patients in poor
      physical condition before the transplant are more likely to suffer the syndrome.
      Surgical technique (standard, venovenous shunt or preservation of the inferior
      vena cava), on the other hand, does not seem to play a major role. Prophylaxis
      with atropine prevents bradycardia but not hypotension. Administration of calcium
      chloride and sodium bicarbonate together with hyperventilation, mitigates
      symptoms. Finally, treatment with phenylephrine is rapidly effective.

PMID- 9011898
TI  - [The discovery of surgical anesthesia and its arrival in Europe. Apropos of the
      150th anniversary of the clinical introduction of ether].
AB  - The clinical introduction of anesthesia took place on the 16th of October 1846 at
      Massachusetts General Hospital (Boston) and William T.G. Morton, a dentist in the
      city, was its discoverer. The news was made public at the beginning of November
      and soon crossed the Atlantic, reaching Paris and London, where there were
      acclaimed medical centers. The event was the object of studies worldwide and
      still today receives the attention of researchers. We have detected numerous
      inaccuracies in most accounts of how anesthesia was introduced in Europe,
      motivating us to undertake the present study to establish a new history of the
      first uses of ether in European countries. We have consulted new bibliographic
      sources and obtained results that are considerably different from those published
      by most authors in recent years. Our analysis and discussion of the findings
      allow us to establish a new chronological account of anesthesia with ether in
      Europe, in which we emphasize the first studies of etherizations performed in
      Belgium, Spain and Italy hitherto ignored by other authors.

PMID- 9011899
TI  - [Anesthesia for cesarean section in a case of Emery-Dreifuss muscular dystrophy].
AB  - We describe the anesthetic technique used in a patient with Emery-Dreifuss
      muscular dystrophy, a rare form whose genetic transmission is usually linked to
      the X-chromosome but which can be dominant, thus occasionally affecting women. A
      woman with vaginal condylomata was scheduled for elective cesarean. She presented
      proximal muscle weakness in the upper extremities, flexion contracture of both
      elbows and neck and, occasionally, respiratory difficulty. Surgery was performed
      with epidural anesthesia with no noteworthy complications. The anesthetic
      implications of this clinical picture depend on the likelihood of malignant
      hyperthermia, difficult intubation, arrhythmias or respiratory insufficiency due
      to muscle weakness. Continuous epidural or spinal anesthesia provides a more
      progressive level of blockade and greater control.

PMID- 9011900
TI  - [Anesthesia for cesarean section in patients with mitral valve prolapse].
AB  - Mitral valve prolapse is the most frequent cardiac valvulopathy. Given its
      greater incidence in young women it is a factor which must be taken into account
      when performing cesarean section. Two patients with mitral valve prolapse in whom
      a cesarean section was carried out are presented: case 1, a 22-year-old woman,
      ASA II, 72 kg, with mitral valve prolapse associated with the Wolf-Parkinson
      White syndrome and an episode of paroxysmal supraventricular tachycardia. The
      cesarean section which was indicated because of the absence of fetal progression
      was performed under epidural anesthesia. Forty-five minutes after regional
      blockade a hypotensive episode was observed which remitted following the i.v.
      administration of 6 mg of methoxamine. No other complication was reported. The
      Apgar score of the neonate at one minute was 7; case 2, a 31 year-old woman, ASA
      II, 51 kg, diagnosed with mitral valve prolapse with no associated
      symptomatology. A cesarean section was performed in this patient because of pedal
      presentation under general anesthesia without complications. The Apgar score of
      the neonate at one minute was 8. The physiopathology of mitral valve prolapse as
      well as anesthesia management during cesarean section in this type of
      valvulopathy is reviewed.

PMID- 9011901
TI  - [Percutaneous femoro-porto-jugular venovenous shunt in orthotopic liver
      transplantation].
AB  - Veno-venous bypass (VVB) by the percutaneous introduction of cannulas in the
      right internal jugular vein during liver transplantation may reduce the
      complications derived from the classical method of axillary vein dissection. The
      results and complications observed over a two and a half year period in 126
      consecutive patients submitted to liver transplantation in whom preparation for
      femoral-portal-jugular veno-venous bypass was carried out are reported. Twelve
      complications (9.5%) were observed in the 126 patients. All the complications
      were due to jugular cannulation and were divided as follows: in 7 patients (5.5%)
      some of the guide introductions were unsuccessful following multiple punctures;
      in 2 patients (1.6%) the right carotid artery was punctured; 2 hemothorax (1.6%)
      were observed and one pneumothorax (0.8%). Forty patients required veno-venous
      bypass. The blood flows obtained during VVB were suffice in all the cases with a
      mean +/- standard deviation of 2.21 +/- 0.44 l/min-1. The technique of femoral
      portal-jugular veno-venous bypass is a good alternative to the classical method
      of the axillary approach. It has advantages such as in the speed of installation
      of VVB and the utility of the large jugular vein during the remainder of the
      surgery for rapid fluid transfusions. Although the number of complications is
      low, they may be important thereby hindering intra management and post operative
      of the patients.

PMID- 9011902
TI  - [Popliteal fossa block. Possible solutions to the postural inconvenience].

PMID- 9011903
TI  - [Effects of metoclopramide on the hypnotic dosages of propofol].

PMID- 9011905
TI  - [Use of ondansetron for prevention of postoperative nausea and vomiting in major
      ambulatory surgery].

PMID- 9011906
TI  - [Lung pathology of organ transplantation: introduction].

PMID- 9011904
TI  - [Diagnostic thoracoscopy].

PMID- 9011907
TI  - [Immunological aspects of lung transplantation].
AB  - The lung transplant is an immunocompetent organ, it induces anomalies of the
      means of defence and a powerful immunological disturbance. After transplantation
      a depression of the means of defence is seen, in particular non-immunological
      with a diminution in certain macrophage functions and the maintenance of a local
      alloreactive phenomenon. During an acute rejection, the graft is the centre of an
      accumulation of effector cells of the allograft reaction. The syndrome of
      bronchiolitis obliterans, associates the presence of these same cells to the
      increase of immunogenicity of the lung transplant. During infections the observed
      anomalies are similar to those seen during a rejection, further more a link
      exists between the pathophysiology of infection and rejection. Overall, lung
      transplantation induces an immunological deficit as is evident by the frequent
      increase of rejections and infections.

PMID- 9011908
TI  - [Intensive care in lung and heart-lung transplantation].
AB  - Intensive care after lung, and heart-lung transplantation may have simple post
      operative course specially after preventive procedures of reperfusion injury,
      nosocomial infections during mechanical ventilation and immunosuppression risks.
      Nevertheless a severe mediastinal shift may occurred after single lung
      transplantation in emphysema. Rapid changes in ventilation/perfusion ratio during
      lung infection or rejection specially in pulmonary hypertension are responsible
      of dramatic respiratory failure. Knowledge of multiorgan dysfunction and
      multidisciplinary experience encourage to future development.

PMID- 9011909
TI  - [Graft dysfunction, acute rejection and bronchiolitis obliterans in lung and
      heart-lung transplantation].
AB  - Three complications which influence both survival and quality of life in
      transplanted patients will be the object of this chapter. Graft dysfunction: this
      is a severe re-implantation oedema leading to inefficiency of the graft as
      regards haemostasis whether or not associated with haemodynamic complications.
      The liberation of free radicals and/or cytokines induced by ischemia-reperfusion
      of the graft plays an important role in the pathogenesis of this syndrome. Acute
      rejection: the mechanism is complex leading to the intervention of an immune
      response stimulated by the detection of allo-antigens. The clinical picture is
      often non-specific. Treatment requires boluses of methyl prednisolone completed
      by decreasing dose of corticosteroid therapy orally. The syndrome of
      bronchiolitis obliterans: this is a progressive failure of the airways. This
      syndrome occurs in the long term in 50% of patients and presents with progressive
      dyspnoea associated with persistent or recurrent cough. The pathogenesis is
      brought about principally by a chronic rejection with a specific cytotoxic
      reaction of T lymphocytes against the airway epithelium which expresses Class II
      major histocompatibility antigens. Attempts at curative treatment can be
      extremely deceptive and leads to, at best, a slowing in decline of respiratory
      function.

PMID- 9011910
TI  - [Infectious complications of lung and heart-lung transplantation].
AB  - Thanks to a simplification of surgical techniques, single or double lung
      transplants have expanded significantly in latter years. Infection remains an
      important cause for morbidity and mortality, more so in early rather than late
      stages. Bacterial infections cause approximately fifty per cent of all
      infections. They can be prevented in part by prophylaxis. Infections to CMV have
      become less frequent thanks to adequate prophylaxis with ganciclovir. Herpetic
      infections are prevented by acyclovir or ganciclovir. A better control of
      immunosuppression seems to be associated with fewer lymphoproliferative disorders
      secondary to the Epstein-Barr virus. Respiratory viruses remain a serious threat
      for these patients, although infections due to respiratory syncitial virus may be
      attenuated by ribavirine. Fungal infections are dangerous but prophylactic
      prescription of azole derivatives have reduced the incidence and severity.
      Prophylaxis of infections to Pneumocystis carinii is essential, the use of
      sulfamethoxazole trimethoprim is efficacious against this as well as nocardiosis.
      Infections to Mycobacterium tuberculosis are often atypical and should be looked
      for and anticipated whenever possible.

PMID- 9011911
TI  - [Endobronchial complications in lung and heart-lung transplantation].
AB  - Bronchial healing is good with heart lung transplantation but this technique is
      actually not often performed. Single lung transplantation and bilateral
      sequential lung transplantation (two single lung transplantations) have at
      present an incidence of anastomotic problems of between 4 and 30%. Efforts to
      improve surgical technique and medical perioperative treatment are described.
      Often the anomalies seen improve by themselves. On the other hand, endoscopic
      treatment is usually performed (dilation, yag laser, cryotherapy, stents) to
      maintain the bronchial airway opened. Precocious resutures, late broncho
      resections of stenosed zones or retransplantations are more rare. Series which
      are for the moment short, of revascularisation of the bronchial arteries during
      the graft seem to give good results.

PMID- 9011912
TI  - [Functional respiratory physiology and physiopathology of lung transplant
      patients].
AB  - Lung transplantation results in dramatic improvement in pulmonary function which
      allows the patients to resume a normal lifestyle. When the lung allograft is free
      of infection and rejection, lung volumes and gas exchange are within normal
      limits after heart-lung and double lung transplantation, both at rest and during
      exercise. After single lung transplantation, lung volumes remain below predicted
      values and some patients show mild oxygen desaturation with exercise. Infection,
      acute rejection, and chronic rejection (bronchiolitis obliterans) produce an
      obstructive ventilatory defect. In addition, there is a bronchial hyperreactivity
      to cholinergic stimulation; this hyperreactivity might be related to airway
      denervation and upregulation of muscarinic receptors or might be triggered by the
      bronchial inflammation induced by rejection. Control of breathing is normal at
      rest, during exercise, in response to CO2 rebreathing, and during sleep. This
      indicates that pulmonary afferents play a negligible role in the control of
      breathing in adult humans. Most transplanted patients show a significant
      reduction in maximum oxygen consumption and have an early anaerobiosis during
      exercise; this response may be accounted for, at least in part, by a persistent
      state of physical deconditioning, and by an inadequate adaptation of cardiac
      output in heart-lung transplant recipients.

PMID- 9011913
TI  - [Lung pathology in heart, liver and kidney transplantation in adults].
AB  - Currently transplantation constitutes the only treatment for terminal heart,
      liver or renal failure. Post-transplantation complications remain numerous and
      sometimes fatal. The rejection of the organ, acute or chronic, and secondary
      infections due to immunosuppression are the most frequent complications that are
      observed. Added to this are the complications of the surgery itself and also the
      non-infectious complications of the immunosuppressive drugs. Pulmonary
      complications contribute an important factor to the post-graft morbidity and
      mortality. The majority of heart and liver transplants develop pulmonary
      complications principally in the first six months after graft. The immediate post
      operative complications such as atelectasis, pleural effusion and pulmonary
      oedema are the most frequent but the infectious complications are much the most
      serious and are responsible for a significant part of the mortality. In renal
      transplantation pulmonary complications are above all infectious and are much
      less common than in cardiac or hepatic transplantation. An early diagnosis of the
      type of complication constitutes a major prognostic factor in immunodepressed
      patients. Thus, the practising pneumologist must thoroughly know the principal
      respiratory complications of solid organ transplant.

PMID- 9011914
TI  - [Lung complications of hematopoietic stem cell transplantation].
AB  - Bone marrow transplantation (BMT) is a potentially curative therapy in selected
      patients with hematologic disorders (acute leukemia, chronic myelogenous
      leukemia, lymphoma) or solid tumors (testicular or breast cancer). Pulmonary
      complications occur in 40 to 60% of patients receiving BMT, and are related to
      various mechanisms: chemotherapy-induced neutropenia, pulmonary toxicity of
      radiotherapy or chemotherapy, graft-versus-host disease. Bacterial or fungal
      pneumonia occurring during the initial period of neutropenia, and interstitial
      pneumonia (related to cytomegalovirus or of unknown origin) are the major
      respiratory complications of the first 100 days. Bacterial sinusitis and
      pulmonary infections, and obstructive airways disease related to bronchiolitis
      are the main late-onset respiratory disorders. No single risk factor can predict
      the development of these complications, which result from a sequence of events
      including infections, pulmonary injuries related to chemotherapy or radiotherapy,
      and inappropriate immunological reaction after transplantation. Antimicrobial
      prevention has been shown to reduce the mortality of these complications, but
      they still result in both important morbidity and mortality. They are the most
      frequent non relapse cause of death among long term surviving patients. Better
      understanding of their pathogenesis, and early recognition and treatment of
      respiratory complications of BMT should improve the efficacy of this therapy.

PMID- 9011915
TI  - [Cytomegalovirus infection and allograft rejection].
AB  - Allograft rejection and human cytomegalovirus (HCMV) infections are two major
      complications of allotransplantation. HCMV infection could promote allograft
      rejection through different mechanisms including the production of several
      proinflammatory cytokines, increased expression of major histocompatibility
      complex and adhesion molecules, and molecular mimicry. Similarly immune
      activation occurring during allograft rejection, its treatment and its prevention
      budget increases rates of HCMV disease. A better understanding of the links
      between allograft rejection and HCMV infection is necessary to develop new
      preventative or curative therapeutic approaches which could improve
      allotransplantation results in humans.

PMID- 9011917
TI  - [Image of the month. Epulis and diapneusia].

PMID- 9011916
TI  - [Aspergillus lung pathology in transplant patients].
AB  - Invasive pulmonary aspergillosis, with or without dissemination to other organs,
      is a severe complication in patients who have undergone transplantation. The
      incidence of this disease is conditioned by the type of transplantation, the
      intensity of immunosuppressive regimens, and local epidemiology. The latter
      factor underscores the importance of air conditioning systems, and special
      caution is needed in case of hospital renovation. The clinical picture is
      frequently characterized by persisting fever, despite antibiotic treatments, but
      is otherwise non specific. Computerized tomography and magnetic resonance imaging
      show typical lesions more often than do conventional chest x-ray films. The
      sensitivity of broncho-alveolar lavage is poor, and DNA amplification techniques
      for Aspergillus might increase the diagnostic yield in the future. Also,
      detection of Aspergillus antigens in serum and urine might prove useful, but
      further studies are needed before a standardized test can be recommended for
      diagnostic purpose. Intravenous amphotericin B is the treatment of choice.
      Liposomal and other lipid formulations of this drug represent interesting
      alternatives, although very expensive. Itraconazole is emerging as a promising
      drug, because of fewer side effects than amphotericin. However, improvement of
      its formulation is still necessary.

PMID- 9011918
TI  - [Pharma-clinics. How I treat... a type 1 diabetic patient with a portable insulin
      pump].

PMID- 9011919
TI  - [Clinical case of the month. Primary sarcoma of the pulmonary artery].

PMID- 9011920
TI  - [Insulin-dependent diabetes].

PMID- 9011921
TI  - [The origin of the concept prion].

PMID- 9011922
TI  - [Neuropathological aspects of prion disease].

PMID- 9011923
TI  - [Prions, molecular aspects].

PMID- 9011924
TI  - [Interspecies transmissibility of spongiform encephalopathies].

PMID- 9011925
TI  - [Thrombotic thrombocytopenic purpura in bone marrow graft rejection (clin
      conference)].

PMID- 9011926
TI  - [Treatment of broncho-pulmonary cancer using carboplatin/etoposide: survival
      analysis].

PMID- 9011927
TI  - [Appearance and health: the role of cosmetics].

PMID- 9011928
TI  - [How I explore... an afebrile difficult infant].

PMID- 9011929
TI  - [Info-congress. Itraconazole in the treatment of dermatomycoses and
      onychomycoses. Current concept of intermittent therapy using weekly units
      repeated monthly].

PMID- 9011930
TI  - [Are there factors which maintain a subjective symptom-free psychological state?
      A study exemplified with HIV-infected subjects].
AB  - AIMS: In the absence of curative treatment, the diagnosis of HIV infection
      imposes a heavy burden. Infected persons are therefore confronted with
      psychological, social and physical problems and cope with them via different
      strategies and social resources. We investigated the question of what factors
      help to maintain a psychologically symptom-free state. METHODS: A sample of 117
      asymptomatic HIV-infected persons was recruited out of the Swiss HIV Cohort Study
      (Part A) in 1989 and 1990. The psychological symptoms were assessed with a self
      rating questionnaire (SCL-90-R). The structured interview focused on social
      network, social support (SONET), and coping strategies (FEKB). RESULTS: 79% of
      the asymptomatic persons did not report psychological symptoms. In multivariate
      analyses, "rumination" (= preoccupational thinking), female gender, and
      affectively negative relationships correlated with more, but affectively positive
      relationships and the strategy "defence against threat" with fewer, psychological
      symptoms. Additionally, there was no significant correlation between the
      immunological markers (CD4-, CD8-cell count, p24 antigen) and psychological
      complaints. CONCLUSIONS: The low number of asymptomatic HIV-infected persons with
      psychological symptoms (21%) is in accordance with other studies. Psychological
      symptoms and rumination correlate significantly in our sample. As rumination is
      difficult to recognize, HIV-infected patients should be directly questioned about
      rumination and their defence against threat should be supported in order to
      prevent the development of psychological symptoms.

PMID- 9011931
TI  - [Hungry-bone syndrome: a nearly-forgotten disease].
AB  - We present a 68-year-old female patient with hyperparathyroidism of many years'
      standing due to nodular hyperplasia of the parathyroid glands. After
      parathyroidectomy the patient developed profound hypocalcemia of long duration
      and was found to have marked cystic bone lesions. The "hungry bone syndrome" is
      rare today and little known to the clinician. It has to be considered in the
      differential diagnosis of postoperative hypocalcemia. We discuss the clinical
      course, therapy and pathophysiology of the syndrome and in particular wish to
      point out the uncommon findings in bone scintigraphy and the unexpectedly high
      calcium requirement.

PMID- 9011932
TI  - [Acute otitis media with effusion: an overview of the pathogenesis and
      recommendations for therapy].
AB  - Otitis media is one of the most common diseases in infants and young children. A
      combination of important factors contributes to the pathogenesis of acute otitis
      media and otitis media with effusion. These are poor tubal function, the degree
      of mastoid pneumatization, nasopharyngeal colonization with pathogenic bacteria
      and viruses, the ascending infectious pathway along the Eustachian tube, the
      immune status of the host, allergic and environmental factors, and genetic
      predisposition. Only correct diagnosis and understanding of they underlying
      pathophysiology enables the clinician to target treatment of the various forms of
      otitis media. We review the current concepts regarding evaluation and management
      of the diseased child and focus on the indication and selection of antibiotic
      therapy, bearing in mind the resistance rate within Switzerland. Most patients
      can be treated medically. "Otitis prone" individuals and children suffering from
      chronic otitis media with effusion with documented hearing loss clearly benefit
      from surgical intervention. We analyze the different treatment modalities and
      present a step-wise treatment algorithm. Newer vaccination trials indicate
      immunogenic effects even in young infants and show promising results in
      experimental and clinical studies.

PMID- 9011933
TI  - [Sex differences in disease course: analysis of the Swiss HIV cohort study].
AB  - The Swiss HIV Cohort Study (SHCS) is a prospective multicentre study of HIV
      infected adults. Participants have been followed up at six-monthly intervals
      since 1988. The purpose of the present study was to examine sex differences in
      developing AIDS-defining events and in survival among participants of the SHCS
      (1042 women, 1507 men). A statistically significant higher risk of Pneumocystis
      carinii pneumonia (PCP) was evident among women. This difference was particularly
      pronounced in 1989 (hazard ratio 2.11, p = 0.01). Other opportunistic events and
      survival showed no statistically significant sex differences. The results are
      compatible with slower introduction of PCP prophylaxis among women. A reason for
      this may be that women were less likely to be enrolled in clinical trials than
      men. This hypothesis will be examined in a further study.

PMID- 9011934
TI  - [Level of stethoscope contamination in the hospital environment].
AB  - The aim of this study was to determine the extent of the contamination of
      stethoscopes and their possible role in transmission of microorganisms. The
      stethoscopes of the medical doctors of the hospital of La Chaux-de-Fonds,
      Switzerland, were cultured and the date of the last cleaning recorded. 38 of the
      62 stethoscopes surveyed were contaminated with microorganisms (61%). The
      majority of isolated organisms were gram-positive bacteria, primarily
      Staphylococcus species (89%). The cleaning of the stethoscopes was frequent for
      32% of the doctors, rare for 46% and non-existent for 22%. After more than one
      day without cleaning of the stethoscope, the level of contamination rose from 0%
      to 69%. Stethoscope use may be an important factor in the spread of infectious
      agents, so that regular disinfection should be carried out (once a day at the
      very least).

PMID- 9011935
TI  - [An unusual presentation of tuberculosis].
AB  - A 67-year-old male was hospitalized because of nonspecific symptoms and bilateral
      pleural effusions. He gave no history of cough, dyspnea or thoracic pain. The
      blood counts showed moderate anemia and high-grade lymphopenia. The tuberculin
      test and the anergy-panel were both negative. Testing for HIV was negative.
      Analysis of pleural fluid showed an exudate with 47% lymphocytes and absence of
      acid-fast bacilli on Ziehl-Neelsen smear. On histologic examination, the pleural
      tissue showed no evidence of granuloma. However, cultures for mycobacteria of
      pleural tissue yielded M. tuberculosis. In this case of pleural tuberculosis,
      leading symptoms were absent and the tuberculin test was negative in the presence
      of active tuberculosis. In addition, the cells in the pleural effusion were not
      predominantly lymphocytic. Patients presenting with unclear effusion should
      undergo extensive investigations, including a tuberculin test, and anergy panel,
      pleural fluid cultures, and pleural biopsy with cultures for microorganisms, with
      the object of establishing or ruling out pleural tuberculosis.

PMID- 9011936
TI  - [At a glance--joint amyloidosis in a dialysis patient].

PMID- 9011937
TI  - [Guidelines for home mechanical ventilation. Swiss Association for the control of
      Tuberculosis and Lung Diseases (ASTP). Swiss Society of Pneumology (SSP)].

PMID- 9011938
TI  - [Bovine virus diarrhea/mucosal disease in cattle--clinical findings in 103 calves
      and cattle].
AB  - One hundred and three calves and heifers persistently infected with BVD virus
      were examined. The most important clinical findings in order of frequency were
      weight loss, erosions of the oral mucosa, diarrhea, anorexia and fever. In
      addition, nasal discharge, lymph node enlargement, erosions of the nose, muzzle
      and interdigital cleft and bronchopneumonia occurred in less than half of the
      patients. Furthermore, crustaceous dermatitis was observed in three patients and
      petechial hemorrhage of the oral mucosa occurred in two other cases with severe
      thrombocytopenia. Haemoconcentration, leukocytosis, hyperfibrinogenemia and
      azotemia were the most important haematological findings. To confirm the clinical
      diagnosis, the serum antibody titre of 69 patients was compared with that of a
      clinically healthy control animal from the same herd. There was no positive
      antibody titre in 65 of the 69 patients, whereas 67 of the control animals had
      positive titres. In 34 patients, EDTA blood samples were collected for virus
      detection. In 20 of these, skin biopsy samples were also obtained for virus
      demonstration. Virus has been demonstrated in the blood of 32 of the 34 cases and
      in all 20 skin biopsy specimens.

PMID- 9011940
TI  - [Field study with a vaccine against enzootic pneumonia of swine].
AB  - The EP vaccine Stellamune Myco was tested in 4 different trials. In a first
      trial, the daily weight increase and the incidence of lung lesions and their
      degree of severity were compared in non-vaccinated and vaccinated pigs
      originating from a herd infected with M. hyopneumoniae. The daily weight
      increases of the vaccinated animals were almost 60 g above that of the non
      vaccinated and the number of altered lungs and the severity of the lung lesions
      was smaller in the vaccinated group. The effects were statistically different. In
      a second trial, no lesions were observed in 60% of the vaccinated animals. In the
      non-vaccinated group, the proportion was only about 35%. More severe lung lesions
      were only present in the non-vaccinated animals. In a third trial, it was
      observed that the animals originating from infected herds may excrete mycoplasmas
      despite the vaccination. In a fourth trial, it was determined that SPF piglets
      were not protected with the vaccination against an infection caused by M.
      hyopneumoniae.

PMID- 9011939
TI  - [Immunohistology as a reliable and efficient method for the diagnosis of BVDV
      infections].
AB  - Persistent infection with the Bovine Viral Diarrhea/ Mucosal Disease Virus (BVDV)
      can be detected using immunohistological methods. The experiments show that the
      LSAB (Labeled Streptavidin Biotin) peroxidase method is suitable to detect the
      BVDV in cryostat sections of unfixed tissue. For the diagnostic work up in living
      animals, skin biopsies give reliable results. In dead animals, organs such as
      thyroid gland, skin, mucosa of the mouth, esophagus and abomasum are well
      suitable for immunohistological BVDV detection.

PMID- 9011941
TI  - [What is your diagnosis? Pyloric obstruction in a domestic cat].

PMID- 9011942
TI  - Sarah Cannon Cancer Center Consensus Conference on Novel Developments with
      Podophyllotoxin Therapy.

PMID- 9011943
TI  - Hormone-refractory prostate cancer: an emerging epidemic. Proceedings from a
      roundtable workshop. Philadelphia, Pennsylvania, May 22, 1996.

PMID- 9011944
TI  - [Laparoscopic operations in pediatric surgery].

PMID- 9011945
TI  - [Acute scrotal syndrome in children].
AB  - The authors discuss different forms of acute scrotal syndrome in child age, its
      symptomatology, differential diagnosis and treatment. They emphasize in
      particular the importance of the time factor in torsion of the testis and the
      necessity of urgent surgery and the difficulty of differential diagnosis. Final
      treatment of children with acute scrotal syndrome should therefore be provided in
      time in a department with sufficient experience with this problem. In the
      department of paediatric surgery in the Thomayer Faculty Hospital in Prague
      during the four-year period (1992-1995) a total of 88 children with acute scrotal
      syndrome were treated. Inflammatory diseases predominated (39%), torsion of the
      testicular and epididymal appendages was recorded in 28%, and torsion of the
      testis in 14%. Children with testicular torsion came to the hospital on average
      20 hours after the onset of symptoms, all were operated but only 58% of the
      testes were saved.

PMID- 9011946
TI  - [Cavernous lymphangioma].
AB  - The authors discuss an extensive cavernous lymphangioma in a two-year-old girl.
      The lymphangioma was in the left half of the trunk. It was was revealed in the
      intrauterine stage by ultrasonography, confirmed on histological examination and
      almost entirely successfully removed by surgical operation.

PMID- 9011947
TI  - [Initial experience with laparoscopic treatment of ileus conditions and lysis of
      adhesions in children].
AB  - Intraabdominal adhesions are important complications after classical laparotomy.
      The authors describe in their paper their initial experience with the
      laparoscopic diagnosis and treatment of intraabdominal adhesions in acute ileous
      conditions in children. Significant adhesions were found in 13 patients. In two
      invagination was the cause of intestinal occlusion. In one patient torsion of a
      loop and in one instance they diagnosed a paracaecal abscess. In the remaining
      three they did not detect the cause of pain after appendectomy. In 2 children
      they had to convert the operation to classical laparotomy. The group is formed by
      children aged 4-17 years. The mean age was 12.3 years. In all instances with a
      positive finding adhesiolysis or solution of another cause of intestinal
      obstruction had a favourable effect and eliminated the patient's complaints.

PMID- 9011948
TI  - [Chronic torsion of an ectopic spleen in the differential diagnosis of abdominal
      pain in a child. Case report].
AB  - Torsion of the spleen occurs in children as a rule in combination with ectopy of
      this organ. It is found in cca one half of the affected children. Abdominal pain
      is always an associated symptoms. Its intensity depends on other factors such as
      the degree of torsion, its duration, the pathophysiology of the process etc. The
      final prognosis can be usually made only during laparotomy. With regard to the
      relatively rare incidence of this disease, the authors submit the case of a
      patient operated in their department.

PMID- 9011949
TI  - [Laparoscopy-assisted appendectomy in children].
AB  - During a 13-month period (March 1, 1995 March 31, 1996) the authors performed in
      70 children a laparoscopically assisted appendectomy. 68 children were operated
      on account of chronic appendicitis, two on account of acute appendicitis. During
      the postoperative period early, not very serious, postoperative complications
      were recorded in 7 children. One girl had on the second day after operation fever
      and severe abdominal pain, four children developed on the 5th-7th day after
      surgery abdominal pain, associated in three instances with fever and in two
      instances with the pathological finding of pericoecal fluid. The complaints
      receded within 1-2 days in all five patients after conservative treatment. In
      another two children the wound healed per secundam intentionem. No late
      complications were recorded.

PMID- 9011950
TI  - [Personal experience with elastic stable intramedullary osteosynthesis in
      children].
AB  - Derived from Ender's elastic nail and from other fixation techniques, elastic
      stable intramedullary nailing (ESIN) provides a combination of elastic mobility
      and stability. The operation uses only small incisions, is rapid, blood loos is
      minimal and physeal area stands intact. Mobilisation using crutches but without
      bearing is allowed as soon as the fracture is painfree and from third week starts
      partial weight-bearing. Between November 1994 and May 1996 21 children with
      femoral shaft fracture, 7 children with tibial shaft fracture and 1 child with
      humeral shaft fracture were admitted to the Pediatric Hospital in Brno and
      treated with ESIN. The guider and the nails from finest quality steel were made
      for us by the czech firm Medin, a. s. to order. We report about our good
      experiences with the ESIN-method.

PMID- 9011951
TI  - [Stenosis and thrombosis of the central venous tract as a cause of manifestations
      of venous hypertension after establishment of an arteriovenous anastomosis for
      hemodialysis].
AB  - The authors draw attention to stenoses and occlusions of the central venous tract
      (subclavicular and brachiocephalic vein) which may be the cause of manifestations
      of venous hypertension on the upper extremity after establishment of an
      arteriovenous anastomosis for haemodialysis. In patients where this condition is
      suspected, careful preoperative examination of the venous circulation is
      essential. Possible treatment is discussed.

PMID- 9011952
TI  - [Aneurysm of the left hepatic artery--a rare cause of hemobilia after
      laparoscopic cholecystectomy: case report].
AB  - The authors draw attention to a rare case when haemobilia was manifested as a
      complication after laparoscopic cholecystectomy and its source was an aneurysm of
      the branch of the left hepatic artery in the region of the third hepatic segment.

PMID- 9011953
TI  - [Acute double perforation of a gastric ulcer].
AB  - The author presents the case of a double perforation of a gastric ulcer combined
      with perforation of the gallbladder altered by inflammation. Operation of the
      second gastric perforation followed 72 hours after the first surgery.

PMID- 9011954
TI  - [How to grasp the gallbladder reliably].
AB  - The authors describe a new laparoscopic instrument to be used for reliable
      gripping of tissue. The instrument is very simple from the technical aspect. Due
      to the firm and reliable grip the preparation of tissue is greatly facilitated.
      This shortens the operation time and is thus less demanding on the patient. The
      instrument is used currently in clinical practice and proved very useful.

PMID- 9011955
TI  - [Amputation of the lower extremities for non-traumatic causes in Slovakia in
      1995].
AB  - The authors submit a questionnaire-based epidemiological study from 61 surgical
      departments in Slovakia, focused on the problem of amputation of the lower
      extremities. The objective of the study was to evaluate indirectly the standard
      of care of diabetic feet in Slovakia. In the study 61 surgical departments
      participated with a catchment area comprising 4,814,000 insured persons, i.e. 85%
      of the Slovak population. In these patients a total of 2116 amputations on
      account of non-traumatic causes were performed (44/100000 population). This
      number included 1578 diabetic patients (74.6%). Minor amputations were performed
      1044 times, incl. 92.2% in diabetic subjects. Major amputations were made 1072
      times, incl. 57.3% in diabetics. The prevalence of major amputations in 1995 was
      21.8/100000 population. The authors recorded a 2.65 fold increase of the total
      number of amputations since 1985. They recorded dissatisfaction with the small
      number of revascularization operations-total 294 (13.9%) which is only one
      quarter of the desirable number. The authors submit their study as the basis for
      a systemic solution of care of the diabetic foot in Slovakia and as a challenge
      for its improvement.

PMID- 9011956
TI  - [Insufficiency of crural perforators: myths, dogma and reality].
AB  - The author evaluates critically ideas on the importance of insufficient crural
      perforators in the pathogenesis of primary varicosities, incl. states with
      chronic venous insufficiency. Based on published facts assessed by
      phlebodynamometry, assessment of the blood flow, duplex sonography and
      plethysmography, the author provides evidence that impaired venous circulation is
      due to reflux in the insufficient saphenous vein. Conversely insufficient crural
      perforators do not cause venous disorders but are due to reflux in the
      insufficient saphenous vein.

PMID- 9011957
TI  - [Treatment of acromioclavicular dislocation with resorbable fixation material].
AB  - The demand of biological treatment of acromioclavicular luxations is met by the
      use of Polydioxanon strips (PDS). Artificial damage of the joint does not occur
      and the bond is elastic. Thus removal of metal which ensures rigid fixation of
      the joint is eliminated. This makes it possible to achieve within a short period
      a normal range of movements.

PMID- 9011958
TI  - [How not to give a lecture or write an article].

PMID- 9011959
TI  - [Ruptured abdominal aortic aneurysm].
AB  - In the years 1990-1994, 43 patients with ruptured abdominal aortic aneurysms
      (RAAA) were operated on at the Department of Vascular Surgery of the Na Homolce
      Hospital in Prague. Men outnumbered women, average patient age was 70 years. The
      mean delay between onset of symptoms and hospital admission counted 27 hrs. Prior
      to transportation, one half to two thirds of patients went through at least two
      types of confirmative evaluation (CAT, ultrasound, angiography) and/or were
      referred via two or more hospital departments. In two thirds of patients profound
      shock with oligoanuria and hypotension were found. Anuria/hypotension proved to
      occur in a significantly lower rate in later survivors compared to later dead
      (11.8% vs. 23.5%: p < 0.05). Persistent hypotension during surgery together with
      eventual resuscitation as well as free blood found within the abdominal cavity
      showed up as further ominous factors. Renal failure was the leading postoperative
      complication (51.2%) with 27.9% of patients requiring hemodialysis after repair.
      Sepsis (25.6%), pneumonia (20.9%) and hemorrhage (13.9%) followed. Twenty-six
      patients were lost (60.5%) either within the first hours and days after surgery
      because of irreversible hemorrhagic shock or between the second and fourth week
      due to the sequels of organ failure and sepsis. In our cohort, regardless of age,
      sex, concomitant disease or the type of surgery, the patient's status on
      admission determined his/her further destiny. Urgent transfer to a specialized
      center going hand in hand with prompt and effective reanimation steps are the
      patient's only hope for survival.

PMID- 9011960
TI  - [Juxtapapillary diverticulum--the effect on endoscopic interventions and
      diagnosis].
AB  - Juxtapapillary diverticula are found in the contemporary population according to
      various sources in 10-20%. Their importance in the pathogenesis of some diseases
      and symptoms is beyond doubt, while in other cases, such as pancreatic diseases,
      it is doubtful. In the submitted material the authors evaluate experience
      assembled during endoscopic examinations and interventions on the papilla Vateri
      implemented in 1988. The authors confirm the more frequent prevalence of
      choledocholithiasis in patients with juxtapapillary diverticula. Juxtapapillary
      diverticula make endoscopic examination as well as possible subsequent
      interventions more difficult. It is necessary to use more complicated procedures,
      specially those with guides. Diverticula may even be the cause of failure or
      complications such as haemorrhage or perforation. For the experienced endoscopist
      there are, however, no decisive impediment.

PMID- 9011961
TI  - [Surgery of inguinal hernia in a clinical department].
AB  - The authors stress on the academic surgical departments the necessity of the
      development of both traditional and minimally invasive techniques of the groin
      hernia repair. They suggest to make patient selection based on the hernia type
      (Nyhus Classification) and patient's will and take account of an internal
      anesthesiologic aspects. From four currently most often applied minimally
      invasive techniques they bring attention to the hernioplasty by exclusively
      extraperitoneal approach, till now seldom used by us.

PMID- 9011962
TI  - [Evaluation of planimetric parameters in various mechanical heart valve
      prostheses].
AB  - Authors make an analysis of 9 currently used mechanical valves and the mounting
      area of the valve is defined as 100%. They compare the following parameters: 1
      area of the fixed part of the prostheses, 2-area of the moving part of the valve
      in open position, 3-effective orifice of the valve. As 4-the parameter is the
      evaluation of number of central opening. Parameters of the primary orifice area
      are the most important. From the results of the study we got the following list
      number: 1 Omniscience, 2 Sorin bileaflet valve, 3 CarboMedics, 4 St. Jude
      Medical, 5 Medtronic, 6 Bicer, 7 Bjork-Shiley Monostrut, 8 B-S sferic disc and 9
      B-S convex-concave valve.

PMID- 9011963
TI  - [External pancreatic fistulae].
AB  - External pancreatic fistulas are feared complications of pancreatic surgery or to
      trauma of the pancreas. In our paper we report on 2 patients suffering of
      external pancreatic fistulas successfully treated by operation. We demonstrate
      the examinations suitable for preoperative mapping of the fistula, the
      possibilities of conservative treatment and the strategy of surgical management
      of the fistulas. During the follow-up time the results of the operation are
      excellent.

PMID- 9011964
TI  - [Surgical complications after kidney transplantation].
AB  - In the period from 1 January 1992 through 31 December 1995, a total of 582 renal
      transplantations were performed at the Department of Cardiovascular and
      Transplant Surgery of the Prague-based Institute for Clinical and Experimental
      Medicine. This number does not include combined kidney and pancreas
      transplantations. In 571 cases, the kidney was transplanted from a cadaveric
      donor while living related donors were involved in 11 cases. Of the 582
      procedures, 515 were first transplantations while the remaining 67 were re
      transplantations. The most frequent surgical procedure was lymphocele developing
      in 70 patients. Urinary fistula was present in 39 patients while 21 patients
      developed early obstruction or stenosis of the ureter. Other complications
      included graft rupture, bleeding, vascular thrombosis and a rare case of bowel
      perforation. Surgical complications required graft nephrectomy in 27 cases
      (4.6%).

PMID- 9011965
TI  - [Polyester-covered spiral Z stent. Initial clinical experience with endovascular
      treatment of aortic aneurysms].
AB  - The authors present their initial clinical experience with endovascular treatment
      of an aneurysm of the abdominal aorta using of a polyester covered spiral Z
      stent. Since May 1995 they treated by the endoluminal route 13 patients with
      aneurysms of the abdominal aorta and 1 patient with thoracic aneurysm. In
      patients with a subrenal aneurysm (n = 10) the stent graft was anchored below
      renal arteries origins. In patients with a juxtarenal aneurysm (n = 3) the stent
      graft was anchored across the renal arteries origins. All patients were followed
      up by angiography, computed tomography and ultrasonography. In one patient with a
      subrenal aneurysm dislocation of the stent graft during implantation occurred. In
      the remaining patients it proved possible to exclude the aneurysm successfully.
      One patient with an juxtarenal aneurysm died 6 days after surgery. The cause of
      death was not associated with the aneurysm or surgery. In patients with
      juxtarenal aneurysms the authors did not observe changes of renal functions or
      occlusion of the renal artery in the course of 12 months.

PMID- 9011966
TI  - National Alliance for Oral Health. Consensus Conference on Medically Necessary
      Oral Health Care. Chicago, IL, April 29-30, 1995. Proceedings and
      Recommendations.

PMID- 9011967
TI  - [Thromboembolytic therapy in acute stroke].

PMID- 9011968
TI  - [Phototherapy of newborn infants with hyperbilirubinemia. Norwegian Medical
      Society].

PMID- 9011969
TI  - [Abdominal compartment syndrome].

PMID- 9011970
TI  - [Shall we discontinue with buffer therapy in heart arrest?].

PMID- 9011971
TI  - [Out-of-hospital buffer therapy in heart arrest].
AB  - The effects of infusing a buffer solution on resuscitability and outcome were
      tested in patients during out-of-hospital cardiac arrest. 502 adults with
      ventricular fibrillation or asystole with failure of first attempt at
      defibrillation were entered into a prospective, randomized, double-blind,
      controlled trial where one group received buffer and the other group placebo
      (saline). 87 of 245 (36%) patients who received a buffer were admitted to
      hospital and 24 (10%) were discharged alive, as against 92 of 257 (36%) admitted
      to hospital and 35 (14%) discharged alive for those who received placebo. Only 16
      of the 502 patients had arterial alkalosis on arrival at hospital and no patient
      had a positive base excess. Patients resuscitated after out-of-hospital cardiac
      arrest had metabolic acidosis but buffer therapy did not improve outcome.

PMID- 9011972
TI  - [Treatment of incterus in newborn infants. Norwegian guidelines in international
      perspective].
AB  - Jaundice is common in neonates and often requires diagnostic and therapeutic
      intervention. Recently a case has been made for less aggressive intervention when
      jaundice occurs in healthy term infants. This issue is also being discussed by
      Norwegian pediatricians. The present paper compares the most commonly used
      guidelines in Norwegian pediatrics with the results of a recent international
      survey of therapeutic practices in cases of neonatal jaundice. The survey
      documented wide variation in the approach to this common problem. Norwegian
      intervention limits for premature/SGA infants are generally at or above the 90th
      centile for the international sample, and must be said to be fairly unaggressive.
      The Norwegian intervention limits for term infants are generally between the
      median and the 75th centile. Thus they are on the less aggressive side of the
      international sample. Though it is likely that many term infants can tolerate
      quite high serum bilirubin levels without significant risk of brain damage,
      arguments for further elevation of the intervention limits are problematic as
      long as we do not have the tools to identify individuals, possibly very few, with
      lower tolerance.

PMID- 9011973
TI  - [Accepted low hemoglobin levels in the perioperative period. A questionnaire
      survey among Norwegian anesthesiologists].
AB  - Declining haemoglobin concentrations are accepted in order to avoid allogeneic
      blood transfusions in surgical patients. A questionnaire was sent to all members
      of the Norwegian Association of Anaesthesiologists addressing the question of
      safe blood levels of haemoglobin in different patient groups, and the different
      blood conservation techniques used in their hospital. 206 questionnaires (49%)
      were returned. Intraoperative and postoperative autotransfusions were the two
      most frequently used methods of saving blood. The survey demonstrates a wide
      diversity in the accepted lower haemoglobin levels, especially in children, and
      in spite of its limitations sheds light on Norwegian anaesthetists' routines as
      regards the indications for blood transfusion and blood conservation in the
      perioperative period.

PMID- 9011974
TI  - [Ablation of the bundle of His in atrial arrhythmia. A solution when the drugs
      fail].
AB  - Radiofrequency ablation of the bundle of His was performed in 33 patients with
      intractable atrial arrhythmias (fibrillation in 23, flutter in seven, atrial
      tachycardia in three). Complete AV block was produced in 30 patients, and
      clinically satisfactory incomplete block in another two. All were subsequently
      treated by pacemaker. The ablation was a failure in one patient with hypertrophic
      cardiomyopathy. Today ablation can be targeted at atrial tachycardias and
      flutter, and ablative modification of the AV node can reduce ventricular rate in
      chronic atrial fibrillation. However, His bundle ablation is still the treatment
      of choice in drug refractory atrial fibrillation when no other measure can
      provide adequate rate control.

PMID- 9011975
TI  - [Treatment of benign prostatic hyperplasia with Proscar (finasteride). Results of
      a 10-year Scandinavian study].
AB  - 707 patients with moderate prostatic hyperplasia were recruited to a two-year
      Scandinavian multicenter study. The study was randomized, prospective and double
      blind. Half of the patients were treated with finasteride (5 mg daily) and the
      controls were given placebo. The patients were monitored with regard to symptoms,
      urinary flow rate and prostate volume. In addition, various laboratory
      examinations were performed. A statistically significant difference was found
      between the groups with regard to symptom improvement and increase in urinary
      flow rate in favour of finasteride. Finasteride reduced prostate volume and
      stopped further growth, leading to a difference of 30% in prostate volume between
      the two groups after two years of treatment. Thus, finasteride was able to stop
      the continuous growth of the prostate in the elderly male. The proportion of
      patients with adverse clinical experiences was similar in both treatment groups.
      However, the finasteride-treated group contained more patients with sexual
      dysfunction. We conclude that finasteride is an alternative to vigilant waiting
      for patients with moderate symptoms of benign prostatic hyperplasia.

PMID- 9011976
TI  - [Arthritis after BCG treatment of bladder cancer. A rare complication].
AB  - Since 1976 intravesical instillation of bacillus Calmette-Guerin (BCG) has been
      used after surgical treatment of bladder cancer. Local side effects like cystitis
      are common, but a small share of the patients develop influenza-like symptoms,
      arthritis and other complications. We describe two patients with arthritis.

PMID- 9011977
TI  - [Priapism. Etiology, diagnosis and treatment].
AB  - Priapism is a condition of prolonged penile erection which often causes pain and
      is unrelated to sexual desire. There is a high risk of impotence despite
      immediate intervention. The incidence has doubled since the introduction of
      intracorporeal injection therapy for impotence. Two subtypes of priapism have
      been described, depending on the underlying cause. The more common type, termed
      low flow, is characterised by inadequate venous outflow, leading to a hypoxic
      painful prolonged erection. The etiology is either idiopathic or related to
      intracorporeal injection therapy. Treatment consists of aspiration and
      instillation of a diluted alpha-adrenergic agent, or surgery, depending on the
      degree of hypoxia. The less common subtype, high flow, is arteriogenic, and
      causes less pain and no ischemia. Injury to a cavernous artery leads to a fistula
      between the artery and the corpora cavernosa. Treatment is either conservative
      with immediate ice pack and compression, or delayed selective embolization of the
      fistula.

PMID- 9011978
TI  - [Use of estrogen in women with systemic lupus erythematosus--should, should
      not?].
AB  - Changes in sex hormone metabolism seem to play a role in the expression of
      systemic lupus erythematosus (SLE). Epidemiological studies have demonstrated an
      increased risk of developing SLE in women using oestrogens for more than ten
      years. Onset or aggravation of symptoms have been described in case reports and
      small retrospective series of SLE patients. Oestrogen replacement therapy is
      generally well tolerated whereas oral contraceptives containing oestrogen can
      induce flares in a small proportion of SLE patients. A generally negative
      attitude towards oestrogens seems inadequate since controlled prospective studies
      are lacking. Patients with stable disease may use oestrogen provided there is
      close follow-up, particularly during the first six months of treatment. Treatment
      with oestrogen is contraindicated in SLE patients with a history of
      thromboembolism, positivity for phospholipid antibodies, and in the presence of
      severe organ involvement.

PMID- 9011980
TI  - [A table of reference values for cost-benefit-analyses in health care].
AB  - On the basis of preference measurements in several countries a table has been
      prepared showing society's assessment of different outcomes in health care as a
      function of severity of illness and effect of treatment. The numbers in the table
      can be used in cost-effectiveness analysis as an aid to deciding allocation of
      resources.

PMID- 9011979
TI  - [Diagnosis and treatment of benign prostatic hyperplasia in general practice.
      Norwegian Medical Society].
AB  - The prevalence of benign prostatic hyperplasia increases with increasing age. The
      growing number of elderly men in the population will cause a marked increase in
      the number of men suffering from this condition. The magnitude of the problem
      necessitates close cooperation between urologists and general practitioners in
      future in order to take care of patients with benign prostatic hyperplasia. The
      purpose of the present survey is to present guidelines for general practitioners
      to enable them to diagnose this condition and to present the various alternative
      treatments currently available. Patients with mild and modest symptoms do not
      need to be referred to an urologist and can be taken care of by the general
      practitioners themselves.

PMID- 9011981
TI  - [Better health for the mother and the child?].

PMID- 9011983
TI  - [Prevalence and incidence].

PMID- 9011982
TI  - [Femoral neck fractures--problems with the official statistics].

PMID- 9011984
TI  - [Is overdose of selective serotonin uptake inhibitors dangerous?].

PMID- 9011985
TI  - [Reduction of cholesterol prevents disease].

PMID- 9011986
TI  - [Unlimited demand for specialists?].

PMID- 9011987
TI  - [Water is half of the food! Vulnerability of the society when many people get
      their nutrition from the same source].

PMID- 9011989
TI  - [Investigation of outbreaks of food-borne diseases].
AB  - Investigation of outbreaks of food-borne disease requires close cooperation
      between the health service and the food control authorities. The primary
      objective is to stop the outbreak and provide a basis for specific control and
      preventive measures. The investigation consists of the following steps: To
      confirm the existence of an outbreak and notify all authorities involved; to
      describe the outbreak according to the variables of time, place, person, and
      agent; to establish an interim diagnosis and identify the etiological agent
      responsible; to assemble all information and establish hypotheses about the
      source of infection using inspections, laboratory investigations, and pilot
      interviews; to test the hypotheses by laboratory-based methods and analytic
      epidemiological approaches; to eliminate the source of infection, implement
      preventive measures, and control that they are efficient; to report the results.

PMID- 9011988
TI  - [Outbreak of food-borne gastroenteritis caused by a Norwalk-like virus.
      Evaluation of methods for confirmation of the etiology in suspected viral
      gastroenteritis].
AB  - Acute gastroenteritis is a common disease and can be food-borne. We describe an
      outbreak of acute gastroenteritis, probably caused by Norwalk-like virus, which
      struck 250 people in the course of one week in a small Norwegian community. The
      source of the infection was probably an infected food handler in a bakery who
      contaminated cream cakes with the virus. The sensitivity of electronmicroscopy
      and analyses of IgG antibodies in serum to detect the etiologic agent was very
      low. The sensitivity to Norwalk Virus Polymerase Chain Reaction was much higher,
      and this was a considerable diagnostic benefit during the epidemic. Close
      cooperation between the local health authorities, the food control authorities,
      the bakery and the public was necessary to diagnose the etiology, source and
      spread of this food-borne infection.

PMID- 9011990
TI  - [Role of food in atopic eczema].
AB  - Some new aspects of adverse reactions to food are reviewed. People quite often
      blame food for the development of allergic symptoms. These true reactions can be
      divided into three groups: Immunological (food allergy--type I-IV reactions), non
      immunological (intolerance--result of non-immunologic mechanisms) and
      toxic/biochemical reactions. The patterns of adverse food reactions are age
      dependent, especially allergy to cow's milk, hen's egg-white and soya, and
      symptoms appear most frequently in children under three years of age. 10-20% of
      children report adverse reactions to food, but only 3-5% have IgE-mediated
      reactions. In children with moderate to severe atopic dermatitis as many as 30%
      are reported to have food allergies. In adults, it is believed that 3-12% may
      have some kind of adverse reaction to specific foods, but only 1-2% have food
      allergy. The most common symptoms of adverse food reactions appear in the skin
      and in the gastrointestinal tract, but respiratory symptoms are also observed.
      Once food allergy has been proven conclusively the identified food should be
      totally eliminated from the diet. If important foods are eliminated the patient's
      sensitivity should be reevaluated again after a time.

PMID- 9011991
TI  - [Drug-induced photosensitivity in Norway. An analysis of reports from the period
      1970-93].
AB  - We have reviewed the data on unwanted side effects of drug therapy, as reported
      to the Norwegian Medicines Control Authority during the period 1970 to 1993. In
      all, 13,000 unwanted side effects were reported during this period. The number of
      recorded side effects was analysed especially in respect of unwanted reactions of
      the skin and appendages, and photosensitive reactions. 799 reported side effects
      involved the skin and appendages. Out of these, 64 reports (8%) were classified
      as being photosensitive reactions. Tetracyclines, diuretics and antihypertensive
      agents were the drugs most often causing photosensitive reactions, although
      several uncommon photosensitizing drugs were also reported. The actual risk of
      photosensitisation is discussed in the light of the prescriptions of these
      substances actually issued.

PMID- 9011992
TI  - [Embolization of cerebral aneurysms. A new therapeutic possibility].
AB  - Treatment of cerebral aneurysms with Guglielmi Detachable Coils (GDC) was
      performed for the first time in Scandinavia in 1992. The experience at Ulleval
      University Clinic from 1994 to 1996 comprises 27 surgically inoperable aneurysms.
      Successful embolization was performed in 20 patients. No complications were seen
      during the procedure. However, renewed bleeding with fatal outcome occurred in
      one patient. In accordance with other colleagues we consider this treatment to be
      unsuitable for wide neck aneurysms (> 5 mm). For this reason seven patients were
      not treated. We conclude that GDC embolization seems to be an effective therapy
      for selected inoperable aneurysms. In the near future the method will probably be
      used to treat some of the surgically operable aneurysms as well.

PMID- 9011993
TI  - [Critical shortage of personnel in nephrology. Assessment of causes of the crisis
      and suggestion for solution].
AB  - The heavier work load for qualified nephrologists in Norway over the last ten
      years is described and compared with the number of positions. The increase in the
      number of dialysis treatments, care of renal transplant patients and other tasks
      performed by qualified nephrologists is roughly doubled from 1985 to 1995. By
      contrast the number of employed qualified nephrologists to pursue the work has
      only increased by 20% over the same period. As of today there is a lack of
      capacity to educate new nephrologists to fill up forthcoming vacancies. When the
      actual need for nephrologists is taken into account, the discrepancy is much more
      serious and will become even more so over the next ten years if no immediate
      action is taken. We suggest the establishment of six new educational positions.
      Altogether, these six new positions will provide the capacity to educate a
      reasonable number of trained nephrologists to meet future challenges, to the
      benefit of patients.

PMID- 9011994
TI  - [Lack of specialists in gastroenterological surgery].
AB  - Despite the fact that a prognosis in 1991 predicted a surplus of ten
      gastroenterological surgeons in 1994, several hospitals are now experiencing a
      lack of applicants. In order to define the scope of this problem, the Norwegian
      Gastroenterological Society and The Specialty Committee for Gastroenterological
      Surgery sent a questionnaire and made a telephone query to all Norwegian Surgical
      Departments in autumn 1995. There were 21 vacant posts and 27 specialists are
      still needed to carry out the tasks the hospitals are instructed to perform. An
      initiative must be taken to increase the capacity and geographical distribution
      of the education and improve the working conditions, and thereby job
      satisfaction, of gastroenterological surgeons.

PMID- 9011995
TI  - [Neurology--may recruitment cover the demand?].
AB  - New therapeutic possibilities have recently been introduced for many neurological
      disorders. The demand for specialists is, accordingly, increasing. To investigate
      the present status, and to give some ideas as to the future recruitment of
      neurologists, a questionnaire study has been performed among all neurological
      departments and their residents. In addition, figures from The Norwegian Medical
      Association have been analyzed. In October 1995, Norway had 209 neurologists, of
      whom 165 were of working age (67 years or younger). Of a total of 115 positions
      for neurologists in regional and county hospitals, 16 were vacant. The posts in
      hospitals with no neurological beds were most frequently vacant. An average of 7
      8 new neurologists are now educated annually. This is slightly higher than the
      annual number of retirements, resulting in a net increase in the number of
      neurologists. However, this positive trend will be reversed as the retirement
      rate increases around year 2010. The residents were generally enthusiastic about
      working with neurological patients and wished to complete their appointments. The
      number of neurologists in Norway is too low compared with international
      standards. In order to obtain a satisfactory neurological service the recruitment
      rate needs to be increased.

PMID- 9011996
TI  - [An outcome of water-borne gastroenteritis in Klaebu].
AB  - In November 1994 a major outbreak of acute gastroenteritis was experienced in the
      municipality of Klaebu (4,486 inhabitants). To investigate the course and extent
      of the epidemic, a questionnaire was mailed to all 1,573 households. The returned
      questionnaires covered 2,943 persons, of whom 1,640 (56%) were reported ill with
      the following most common symptoms: Nausea (83%), vomiting (78%), diarrhoea (72%)
      and abdominal pain (70%). The epidemic curve was typical of a common source
      epidemic. The incidence of vomiting turned out to have three distinct peaks with
      an interval of 26 hours, probably due to secondary infections. Two specimens that
      were examined by electron microscope showed typical Norwalk virus structures, and
      this virus was assumed to be the etiologic agent. The actual cause of this common
      source epidemic was found to be inadequate chlorination. The onset of symptoms in
      different parts of the municipality showed that time taken for the infection to
      be transported from the reservoir to the consumers was longer than expected. Such
      delays allow for information on preventive measures to be communicated via the
      radio and other media.

PMID- 9011997
TI  - [Water-borne campylobacter infection--probably caused by pink-footed geese. Two
      outbreaks in Nord-Trondelag, Stjortdal in 1994 and Verdal in 1995].
AB  - The authors describe two water-borne outbreaks of Campylobacter gastroenteritis
      that occurred in central Norway in 1994 and 1995. The epidemics were probably
      caused by contamination of drinking water by the stools of Pink-footed geese on
      the way from Svalbard to Germany-Netherlands. Campylobacter jejuni from the
      stools of the geese was transmitted to the population via untreated drinking
      water, causing disease in 50% of the population. About 1,000 persons suffered
      from gastroenteritis caused by contaminated drinking water in these two
      epidemics.

PMID- 9011998
TI  - ["Stockholm open" in prioritization].

PMID- 9011999
TI  - [Global medical ethics? Reflections on points in common between Bhutan and
      Norway].

PMID- 9012000
TI  - [Should we measure bone density in all women?].

PMID- 9012001
TI  - [Do you treat your vitamin B12 patients correctly?].

PMID- 9012002
TI  - [Helicobacter pylori and stomach ulcer--diagnosis and treatment in primary health
      care].

PMID- 9012003
TI  - [Missing medical record].

PMID- 9012004
TI  - [Handling out epicrisis without the consent of the psychotic patient].

PMID- 9012005
TI  - [Pioneers: veterinarians from earlier times (19). Philibert Chabert (1737-1814)].

PMID- 9012006
TI  - [Pets; a spiritual and physical blessing].

PMID- 9012007
TI  - [Veterinary medicine a fantastic science].

PMID- 9012009
TI  - [Cattle breeders vaccinate].

PMID- 9012008
TI  - [Equine arteritis virus: clinical symptoms and prevention].
AB  - Sero-epidemiological surveys have revealed that equine arteritis virus (EAV) is
      prevalent in most European countries. The virus causes sporadic cases of
      respiratory disease and abortion in horses, the incidence of which has increased
      in recent years. Mares and geldings eliminate virus after acute infection, but
      30% to 60% of stallions become persistently infected. In these animals, EAV is
      maintained within the reproductive tract and is shed continuously in the semen.
      Persistent infection with EAV in stallions has no negative consequences for
      fertility but mares inseminated with virus-contaminated semen can have an acute
      infection. These mares shed large amounts of virus in respiratory secretions and
      urine, leading to lateral spread of the virus to other susceptible horses. Acute
      infection at later stages of gestation can lead to abortion. Effective control of
      the spread of EAV infection depends on the identification of virus-shedding
      stallions. Persistently infected stallions should not be used for breeding or
      should be bred only to seropositive mares. Mares bred to shedding stallions
      should be isolated from other animals for a period of 3 weeks following
      insemination to prevent the lateral spread of EAV.

PMID- 9012010
TI  - [Cattle farmers vaccinate].

PMID- 9012012
TI  - Nomenclature for factors of the HLA system, update June 1996.

PMID- 9012011
TI  - [Lyme borreliosis in dogs].
AB  - In a 2-year-old Bernese Mountain dog the diagnosis of Lyme borreliosis was made,
      using the criteria that are mentioned in the literature: seropositivity in the
      presence of the typical clinical symptoms, with infestation of ticks in the
      history. The usual therapy of amoxycillin or tetracyclines was inadequate and did
      not resolve the clinical symptoms, possibly as a result of a combination of
      initial corticosteroid therapy, the clinical presentation of the disease (mainly
      meningitis), and a presumed immuno-incompetence often seen in this breed.
      Intravenous treatment with amoxycillin finally led to total cure of the disease.
      Lyme borreliosis recurred half a year later, presumably as a result of a new tick
      infestation. A review of the literature on Lyme borreliosis in humans and dogs is
      presented. The fact that Lyme borreliosis in dogs in the Netherlands has not been
      diagnosed often and has not been reported before may be due to differences in
      approach to human and canine patients with fever.

PMID- 9012014
TI  - [The clinical case. European shorthair tomcat, 10 years old].

PMID- 9012013
TI  - [Vaccines against parasitic diseases of domestic animals].
AB  - This review presents short information on the present status and some future
      perspectives of vaccination against parasitoses of domestic animals. For the
      control of such parasitoses in some European countries only a few vaccines are
      registered: Paracox and Livacox (for coccidiosis in chickens), Toxovax (for
      toxoplasmosis in sheep), Pirodog (for babesiosis in dogs) and Dictol (for
      dictyocaulosis in cattle). These are live vaccines containing attenuated
      parasites, except Pirodog. As a world-wide innovation in 1994 a vaccine against
      ixodid tick infestation (Boophilus microplus) in cattle was marketed in Australia
      under the trade name TickGARD which contains a recombinant protein antigen. A
      recombinant vaccine against Taenia ovis cysticercosis in sheep was developed in
      Australia/New Zealand but has not yet been registered. The development of
      vaccines against further parasitoses of domestic animals is a fascinating and
      promising field. Present research activities are focussed on molecular antigen
      vaccines and vector vaccines. First reports (for example regarding leishmaniosis
      and malaria) indicate that nucleic acid vaccines represent a new potential of
      development.

PMID- 9012015
TI  - [Possibilities for the us of laser surgery in veterinary medicine. Part 2:
      Effects of laser beams on tissue].
AB  - The effect of a certain laser beam on tissue is dependent on the different
      properties of the tissue. The various kinds of laser radiation are absorbed from
      different components of an organ. Only where absorption takes place there will be
      a transformation of the energy of radiation to other forms of energy and changes
      in tissue will occur. The arising thermal energy not only heats the area exposed
      to the laser beam but the surrounding tissue. The extent of the heating effect on
      tissue is due to properties of the tissue, e.g. the degree of blood supply and
      with it the draining of heat, and the parameters of the laser system, e.g. time
      of exposition and power of radiation. By increasing power of radiation the effect
      will be an unspecific heat stimulation, coagulation of tissue up to vaporization
      of tissue. By using different ways of transmission the effects produced by laser
      will change and can be adapted to various medical and anatomical requirements.

PMID- 9012016
TI  - [Distribution of influenza C virus infection in dogs and pigs in Bavaria].
AB  - 150 dog and 240 pig sera were tested for antibodies against influenza C virus in
      the hemagglutination inhibition test and confirmed by immunofluorescence and
      Western blotting tests. Virus strain C/JHB/1/66 was utilized as a standard
      antigen. It was found that 50.6% of the total number of dogs in the age between
      one month and 14 years possessed antibody titers of 1:20 or more, which was set
      as the general cut-off. In comparison, 24.0% of pigs in the age between one day
      and one month (n = 90) and 25.9% of pigs in the age between one month and one
      year (n = 150) were found to be positive. The highest hemagglutination inhibition
      titer was determined as 1:320 for of the dog sera and 1:160 for of the pig sera,
      respectively.

PMID- 9012017
TI  - [Wild horse or domesticated horse? Horse remains from the neolithic settlement in
      Pestenacker, Bavaria].
AB  - The bone finds from the neolithic settlement in Pestenacker (near Landsberg am
      Lech) date back to the second half of the 4th millennium BC (Altheim). Like in
      any other late neolithic horse bones, the question we have to deal with is
      whether they represent the remains of wild horse or early domestic horse, as we
      do not know for certain yet the date of the earliest domestic horses' occurrence
      in Middle Europe. The post pleistocene distribution of the wild horse is
      described. For a long time people thought that hardly any wild horses existed in
      post pleistocene Middle Europe any longer, due to the increasing amount of
      woodland. However, recent research has corrected this hypothesis. Three criteria
      the horse bones' share in the total amount of bone finds, the pollen-analytic
      reconstruction of the former environment, and the size of the bones-serve to show
      that the bones most probably represent wild horses which at that time lived on
      the gravel terraces along the river Lech.

PMID- 9012019
TI  - [Comparative determination of creatine kinase activity in the cerebrospinal fluid
      and in the blood of health cattle].
AB  - Cerebrospinal fluid (CSF) was obtained by puncture of the canalis vertebralis at
      the lumbosacral foramen. The activities of creatine kinase (CK) in CSF and plasma
      samples of 68 healthy cattle of different age and breeds were analysed. No
      significant correlation between CK activities of CSF and plasma was found. The
      obtained CSF were classified macroscopically into groups of clear-colourless,
      flaky-colourless, and bloody-flaky samples. The CK activities of clear-colourless
      CSF showed a normal distribution and were used for further analysis. The range of
      standard values of CK activities in CSF (0.2-18.7 U/I) was defined after
      identification of runaways and narrowing of random sample to 95%.

PMID- 9012018
TI  - [The effect of subclinical and acute ante partum acidosis in cows on the course
      of pregnancy with regard to the steroid hormone profile].
AB  - Experiment 1: In a field experiment in 19 of 87 cows being in day 260-265 of
      pregnancy subclinical metabolic acidosis was found. The control group included 10
      healthy cows in the same stage of pregnancy. Blood samples from cows of both
      groups were collected once daily until day 2 post partum for determination of
      oestrogens, progesterone and cortisol. Dystocia was found in four and retained
      placenta in three cows having acidosis. These cows had lower oestrogens and
      markedly higher cortisol and progesterone concentrations during parturition.
      Course of pregnancy and delivery in control cows an without any difficulties and
      hormonal profiles in these cows were typical. Experiment 2: On day 265 of
      pregnancy experimental acute acidosis was evoked in five cows and five other cows
      served as control. Sampling of blood was the same as in experiment 1. Acidosis
      caused on day 269 in two cows premature birth with retained placenta. Moreover
      concentrations of studied steroids were atypical. In three other cows with
      acidosis course of pregnancy and delivery was without any trouble. Only cortisol
      was increased while progesterone and oestrogen values were in agreement with
      concentrations of control cows. Data suggest that metabolic acidosis can cause
      dystocia, premature birth and retained placenta. Furthermore, acidosis clearly
      affects the profile of steroid hormones.

PMID- 9012020
TI  - [Hyperplasia of the ruminal villi in three wild roe deer].
AB  - In autumn 1994 a hyperplasia of ruminal villi in three roe deer out of one
      hunting ground was diagnosed. The ruminal villi were three to five times longer
      than normal and partially stuck together. The case history and a comparison of
      the pathomorphological and histological findings with similar symptoms in
      domestic ruminants lead to a discussion on feeding as the cause of the disease.

PMID- 9012021
TI  - [The cerebrospinal fluid from healthy pigs and pigs with central nervous system
      diseases].
AB  - CSF samples were taken from 50 healthy pigs of both sexes and cytologically and
      biochemically examined. With the aid of regression calculations it was
      investigated, whether deep freezing of CSF samples influences the laboratory
      results. The parameters glucose, urea, creatinine, total protein, magnesium,
      anorganic phosphate, AST and AP were in good agreement with the values of the
      original samples exhibiting only slight variations. Minor age relationship was
      only seen with respect to the two enzymes LDH and HBDH. A linear relationship was
      found between values in CSF and in serum of the parameters urea, creatinine,
      sodium and potassium. CSF examination should include cell count, Pandy's test and
      bacteriological investigation as well as the determination of the levels of the
      enzymes LDH and HBDH. The activity of the enzymes AST and ALT increases along
      with the severity of the tissue damage (meningitis). The specific gravity
      increases similarly to the total protein level in cases of chronic compression of
      the spinal cord, and Pandy's test becomes positive. However, CSF glucose levels
      are partly reduced in animals with central nervous symptoms. The levels of the
      enzymes AP and CK are often increased in central nervous disturbances, but do not
      admit drawing a conclusion on the degree of damage.

PMID- 9012022
TI  - [The plasma level of kanamycin after intravenous and intramuscular injections in
      horses].
AB  - A therapeutical dose of kanamycin was tested intravenously and intramuscularly in
      four normal standardbreds and plasma concentrations were measured over a 12 hour
      period. Plasma levels exceeded a minimum inhibitory concentration of 4
      micrograms/ml within only 15 minutes for 8 hours both after i.v. and i.m.
      injection. Kanamycin revealed a mean plasma half life of 2.3 hours.
      Bioavailability of an intramuscular dose was about 76%. The pharmacokinetic
      parameters demonstrate the rapid onset of antibacterial plasma levels of the test
      compound. A dose regimen for horses of two times daily 5 mg/kg body weight
      ensures therapeutically effective plasma levels. The risk of accumulation as well
      as nephro- or ototoxic side effects are negligible at short-term treatment.

PMID- 9012023
TI  - [Sonographic demonstration of an aortic thrombosis in the dog].
AB  - A case of aortic thrombosis in a Golden Retriever is reported. The main clinical
      signs were paresis of the left hind limb, weak femoralis pulses and cool distal
      limbs. The diagnosis was made by ultrasonography. An echogenic, intraluminal mass
      was detected in the iliac bifurcation.

PMID- 9012024
TI  - [The ultrasonic diagnosis of foreign bodies in the dog and cat].
AB  - For the search of foreign bodies by means of ultrasound the 5 resp. 7.5 Mhz
      transducers are best used depending on the position. The appearance of different
      materials in the echotomogram such as plant parts, wood, metal or plastic is
      described. While in the abdominal organs, excluding the intestinal tract, a
      foreign body can be well detected, it can however only be visible in the
      abdominal cavity, when the surrounding tissue is inflamed (such as granuloma,
      abscess, free fluid). The ultrasound was only able to detect foreign bodies in
      the intestinal tract in approximately half of the cases. In those cases secondary
      sonographic signs of an ileus are often decisive. Penetrating foreign bodies in
      the area of the soft tissue of the musculoskeletal system are evaluated in the
      ultrasound according to their position, size and form. They are best seen when
      the inflamed reaction-line is well developed. Probes and catheters are
      definitively detected in the sonographic examination. Their position can be
      checked.

PMID- 9012025
TI  - [Modification of the quality indicators of the ejaculate of beagle dogs due to
      frequent collections over time].
AB  - Ejaculates from five adult beagle dogs were investigated for changes of
      spermatologic parameters. Semen was collected daily during 12 weeks. The
      parameters volume, sperm count, and transmigration rate (TMR) increased during
      the first three to five weeks and decreased in the middle of the experiment. The
      percentage of morphologically abnormal spermatozoa just exceeded 20% from the
      fifth to the seventh week and in the tenth week, respectively. Either the results
      remained on a low level (volume), or they returned to normal from the tenth week
      on (morphology, TMR, sperm count). Semen quality diminished after five weeks. It
      is concluded, that daily semen collections during more than five weeks can cause
      decreased libido, aspermia, and impairment of the conception rates.

PMID- 9012026
TI  - [Validity of diagnostic methods for kidney function tests in the cat].
AB  - The diagnosis of kidney disease is difficult in the stage of compensation and
      impossible based solely on the routinely performed laboratory tests on blood and
      urine. For this reason, more sensitive methods are required. In the present
      study, three special techniques are compared with regard to their validity in the
      early diagnosis of kidney disease in the cat: 1. the molecular-weight related
      separation of urine proteins with the sodium-dodecyl-sulfate-polyacrylamide
      gradient gel electrophoresis (SDS-page) in the PhastSystem, 2. measurement of the
      glomerular filtration rate (GFR) with the renalyzer PRX90 using an iodine
      containing contrast medium and 3. kidney scintigraphy. The results of this
      comparison demonstrate that these procedures are important adjuncts to common
      laboratory investigations in the testing of renal function. The SDS-page allows
      an early qualitative assessment on alterations of specific functional
      compartments of the kidney. However, it is not possible with this method alone to
      evaluate the degree of renal disturbance and it does not give information
      concerning the severity of renal functional impairment. Measurement of the GFR is
      also a valuable procedure which gives a quantitative result on the global renal
      function within a few hours. It is of special importance when subclinically
      disturbed kidney function is present. In the cat however it is until now not
      possible to give a correct prognosis in high grade nephropathies. Only
      scintigraphy allows unilateral assessment of renal function, which is most
      important in cats with morphologically altered kidneys, such as kidney cysts,
      hydronephrosis or tumours.

PMID- 9012027
TI  - [Blood parameters as an aid in the diagnosis of reptile diseases].
AB  - As ill reptiles only show nonspecific clinical signs, blood chemistry parameters
      are a valuable help in diagnosis. Practicable sites for obtaining blood of
      snakes, sauria and chelonians are vena coccygealis ventralis and cardiac
      puncture, of chelonians also vena jugularis, axillaris and coccygealis dorsalis.
      The following blood parameters were investigated: number of erythrocytes and
      leucocytes, urea, uric acid, creatinine, AST (GOT), ALT (GPT) GLDH, AP, total
      bilirubin, CK, LDH, lipase, alpha-amylase, calcium, phosphorus, sodium,
      potassium, chloride and total protein. Especially for diagnosing nephropathies
      evaluation of urea and uric acid proved to be valuable.

PMID- 9012028
TI  - [Measurement of selected enzymes in blood plasma of cats in the first six months
      of life].
AB  - In this study, amylase, lipase, ALT, AST, GGT, AP and GLDH were measured in
      plasma of male and female cats during the first six months of life. The
      determined reference values ranged at the upper level of those in literature or
      above. Associations with age were found in some enzymes.

PMID- 9012029
TI  - [Comparison of standard methods for the preparation of egg yolk antibodies].
AB  - Chicken egg yolk antibodies (lgY) play an increasing role as alternative to
      mammalian polyclonal antibodies. They are widely used in biomedical research, for
      diagnostics, prophylaxis, and therapy of diseases. The extraction steps of IgY
      from egg yolk must be simple, with high output of purified antibodies. The aim of
      the present study was a comparison of different purification methods of egg yolk
      antibodies. The results of eight extraction methods of IgY and method
      combinations were investigated by PAGE and densitometric analysis. It has been
      demonstrated, that the IgY preparation with dextran sulfate is very effective,
      quick and simple to perform. It is well-suited in combination with other methods,
      e.g. ammonium sulfate precipitation.

PMID- 9012030
TI  - [Pharmacologically induced erection].

PMID- 9012031
TI  - [General skin cancer. Quantity, treatment and quality].

PMID- 9012032
TI  - [Ovarian hyperstimulation syndrome (editoria)].

PMID- 9012033
TI  - [Ovarian hyperstimulation syndrome--prevention and treatment].
AB  - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic, potentially life
      threatening condition associated with ovulation induction. With increasing
      numbers of women receiving various ovarian stimulation protocols as part of
      different infertility treatments, the number of cases is likely to increase. The
      syndrome has a wide spectrum of clinical and laboratory findings, and is
      classified into mild, moderate and severe OHSS. The pathophysiology of this
      syndrome is unclear, and medical management has traditionally been conservative
      and supportive consisting of bedrest, volume expanders and replacement of fluid.
      When ascites is present, paracentesis under ultrasound guidance has been found to
      improve the condition of the patient by reducing the hydrostatic pressure.
      Prevention is very important, but at present it is doubtful if OHSS can be
      completely avoided due to the existence of a relatively small margin of safety
      between successful induction of ovulation and the development of OHSS.

PMID- 9012034
TI  - [Lightning injuries. Mechanisms and treatment].
AB  - Lightning injuries occur sporadically and are rarely seen in emergency
      departments, during the years 1991-1993 there have been 12 admissions due to this
      cause in Denmark. The special mechanisms of damage in lightning accidents are
      illustrated by review of the literature. The clinical findings are described,
      especially the transient neurological damage characterises lightning accidents.
      Contrary to what one would expect, the victim often survives a lightning
      accident. This is surprising considering the tremendous powers of nature involved
      and the serious clinical manifestations. Prevention is important, this is the
      reason why the population should be taught the appropriate behaviour if there is
      a thunderstorm. Resuscitation should be started immediately and continued even
      though the victim seems lifeless and might have dilated pupils not reacting to
      light. Good results have been reported even after prolonged resuscitation.

PMID- 9012035
TI  - [Results of treatment of non-melanoma skin cancer in a dermatologic practice. A
      prospective study].
AB  - The study was carried out to determine the results of treatment of a cohort of
      patients with histologically verified non-melanoma skin cancer diagnosed and
      followed prospectively for two years in a private practice of dermatology.
      Throughout the follow-up period, any new non-melanoma skin cancers among this
      cohort were recorded. Six hundred and forty-six consecutive patients seen in the
      Dermatology Clinic, Vesterbro 99, Aalborg, Denmark, from July 1, 1990, to June
      30, 1993, had a total of 768 tumours that were histologically verified as basal
      cell carcinoma, squamous cell carcinoma or Bowen's disease. Six hundred and
      twenty-eight tumours in 526 patients were treated in our clinic, 91% of these
      with curettage followed by electrocautery. Hundred and twenty patients with a
      total of 140 tumours were referred to a local hospital for treatment. Thirty-six
      of the 508 basal cell carcinomas treated in the clinic recurred during the follow
      up period, and one mixed tumour (basal cell and squamous cell carcinoma)
      recurred. During the follow-up period, 151 new non-melanoma skin cancers were
      detected. In addition, 10 patients each developed 10 or more new tumours.

PMID- 9012036
TI  - [Perinatal mortality in Denmark. An analysis of development assessed in
      connection with medically induced abortion during the period 1980-1993].
AB  - Based upon data from the Danish National Register of Causes of Deaths, the Birth
      Register and registers on induced abortions and congenital malformations the
      article analyses the trend in the Danish perinatal mortality and the impact of
      abortions induced on medical grounds during the period 1980-1993. Estimating that
      half of the induced abortions might have led to a perinatal death it is concluded
      that the perinatal mortality would still have been significantly reduced from the
      late 1980s to 1990-1993. It is stressed that the impact of induced abortions be
      included in analyses of trends in perinatal mortality. The perinatal deaths are
      classified in nine categories by which a grouping into non-avoidable (unexplained
      intrauterine deaths and deaths due to congenital birth defects) and avoidable
      deaths (all other categories) was possible. The classification mixed
      pathoanatomical, obstetrical and paediatric criteria and facilitated an
      evaluation of the trend in mortality in relation to health care. The recent
      decrease in the overall perinatal mortality to 7.5 per 1.000 born was both due to
      a fall in deaths caused by prematurity and in deaths due to congenital birth
      defects. The deaths due to prematurity were not significantly linked to maternal
      smoking during pregnancy and no differences could be found in the overall
      prenatal screening between mothers who lost a baby due to malformations and all
      mothers.

PMID- 9012037
TI  - [Infant mortality among children of 35-39 year-old mothers. An analysis of
      development of death cause categories and among multiple pregnancies during the
      period 1980-1993].
AB  - The perinatal mortality in Denmark decreased significantly from the late 1980's
      to 1990-1993 but increased among births by mothers aged 35-39 years, from 9.7 in
      1985-1989 to 11.0 per 1000 born in 1990-1993. No increase was observed among
      infants of teen-age mothers or mothers older than 40 years. Based upon data from
      the Danish National Register of Causes of Death and the Birth Register all
      perinatal deaths in 1980-1993 were classified in nine categories including
      pathoanatomical, obstetrical and paediatric criteria. The increase in perinatal
      mortality in infants born to mothers aged 35-39 years was because of more deaths
      due to congenital birth defects, intra-partum events and foeto-placental
      dysfunction, while mortality due to prematurity decreased. The rate of multiple
      pregnancies and of primiparas increased significantly among 35-39 year-old
      mothers. With reference to international literature, the article discusses the
      possible impact of in-vitro fertilisation and other fertility treatments upon the
      special trend in perinatal mortality in this mother age-group. A national Danish
      IVF-register was first established in 1994 and will in the future allow concrete
      analyses of the outcome of IVF-pregnancies.

PMID- 9012038
TI  - [Long-term results after Charnley hip replacement].
AB  - We made a prospective study of 241 Charnley total hip replacements performed
      between 1968 and 1974. In 1990 we reviewed 92 patients with 103 hips or 96% of
      surviving hips at a mean follow-up of 17.6 years (15 to 20.6). The clinical
      results were excellent with Charnley scores of four or more for pain in 95% of
      the cases, for function in 73% and for movement in 93%. Of the whole series, 8.3%
      had been revised and Kaplan Meier survival analysis showed a probability of
      revision at 20 years of 10.7%. No significant difference concerning the results
      was found between young patients operated between the ages of 34 to 55, and older
      patients operated between the ages of 56 to 79 years. These results are similar
      to those from the few other series with extended follow-up and make it difficult
      to justify the present widespread use of uncemented hip prostheses.

PMID- 9012039
TI  - [Scalds in children caused by water from toppled electrical kettles. Mechanisms,
      costs and preventive measures].
AB  - Since 1988 a new type of burns in children has been recorded at the Burns Centre
      at Hvidovre Hospital in Copenhagen, being scalds caused by water from toppled
      electrical kettles (el-kettles). The children with el-kettle scalds were younger
      and their injuries more severe than those of children whose scalds had other
      causes. During the six year period 1988 to 1993, a total of 29 children (0-3
      years) have been admitted with scalds caused by el-kettles, 15 children alone in
      1993. The costs for treatment have been more than 3 million Danish kroner, 1.8
      million DKK alone in 1993. From 1993 preventive measures were taken to reduce the
      number of this type of scalds. Since the number of households with el-kettles in
      Denmark is on the increase, an increasing number of toddlers with severe scalds
      could be anticipated. However, a fall in the number of children admitted was
      registered in 1994 (four children) and 1995 (six children).

PMID- 9012040
TI  - [Rational transfusion therapy. A study of transfusion practice and possibilities
      of optimization in elective coronary bypass surgery].
AB  - The objective of the study was to evaluate the effect of intervention on
      physicians' transfusion behavior in elective coronary artery bypass grafting
      (CABG). We analyzed transfusion data on 176 patients who underwent primary
      elective CABG during two periods, either before (phase one, n = 102) or after
      (phase two, n = 74) intervention. The intervention was based on cooperation with
      the involved department of cardiac surgery, interviews of the surgeons and
      anaesthesiologists ordering blood, and concurrent audit of transfusion practice
      using a blood order form. The proportion af patients receiving allogenic
      transfusions decreased from 90% in phase one to 58% in phase two and the total
      use of blood components was reduced from an average of 6.3 units/patient to 2.7
      units/patient, p < 0.01. Indications for transfusion documented in the medical
      record increased from 19% in phase one to 63% in phase two. It is concluded that
      intervention on physicians' transfusion behavior can improve the transfusion
      therapy in patients who undergo elective CABG.

PMID- 9012041
TI  - [CT in the initial diagnostic evaluation of trauma].
AB  - Thirty-eight multi-traumatized patients admitted to the Emergency Room at the
      county hospital in Vejle underwent computerized tomography (CT) after a standard
      protocol in the initial evaluation. Eighteen patients were intubated during CT.
      Eighteen patients had positive findings in more than one of the regions of the
      body. In total 35 positive findings were made in the 38 patients. Our procedure
      of CT-scanning multi-traumatized patients is described and the use of CT in the
      initial evaluation of the multi-traumatized patient is discussed. We find that CT
      with a standardized procedure supplements the clinical evaluation with important
      information about potentially life-threatening conditions some of which may be
      clinically unexpected. Prior to CT the patient must be stabilized in the
      Emergency Room. After that CT is a simple modality, which furthermore is fast and
      safe to perform.

PMID- 9012042
TI  - [Lightning accidents in ]rhus 1991-1993].
AB  - During the years 1991-1993, the emergency department of Arhus Kommune Hospital
      received four victims of lightning accidents. Two of these were admitted to the
      intensive care unit for further treatment and observation. This case report
      brings their histories including clinical findings. Possible mechanisms of damage
      are discussed and the importance of immediate and continued resuscitation of the
      presumably lifeless victim of a lightning accident is confirmed. All four
      patients recovered without serious physical sequelae.

PMID- 9012043
TI  - [Genetic test as a guide for surgical management in familial adenomatous
      polyposis].

PMID- 9012044
TI  - [Bell's palsy treated with acyclovir].

PMID- 9012045
TI  - [Diagnosis of secondary aorto-intestinal fistula].

PMID- 9012046
TI  - [Hallux valgus and other disclocations].

PMID- 9012047
TI  - [Pharmacologically induced erection--therapeutic use].

PMID- 9012048
TI  - [Why is strong licorice not healthy for children].

PMID- 9012049
TI  - [It's never too late. Possibilities for improvement of functional abilities in
      the elderly].

PMID- 9012050
TI  - [Smile--and hope for a miracle].

PMID- 9012051
TI  - [Consultant service in research methodology and statistics].

PMID- 9012052
TI  - [Medical research in Greenland--circumpolar health].

PMID- 9012053
TI  - [Nobel Prize for discovery of the cell-mediated immune defence].

PMID- 9012054
TI  - [Methaphors and understanding of diseases].
AB  - In the recent two decades it has been argued that our language and sense of
      reality is radically structured by metaphors. Metaphors are not just figurative
      expressions of existing similarities, but can create such similarities. Certain
      metaphors (root metaphors) may convey new world views and thus underpin new
      theoretical formations. The article goes through a series of metaphorical
      descriptions of illness, and elaborates on the importance of metaphors for
      medical communication and language-use. The significance of the metaphors for
      communication between physician and patient is lined out, and it is described how
      the use and subsequent rendering of metaphors from two different structures of
      understanding may lead to serious misapprehension.

PMID- 9012055
TI  - [Improvement of functional abilities after treatment of depression in the
      elderly].
AB  - During one year all patients with a diagnosis of depression in accordance with
      ICD-10, referred to a psychogeriatric department, were assessed at admission and
      discharge with a number of rating scales: The Brief Geriatric Depression Scale,
      Katz' ADL-index, the Multidimensional Dementia Assessment Scale, the Mini-Mental
      State Examination and the Functional Ambulation Classification. The department
      has an active stepwise treatment strategy: SSRI (selective serotonin reuptake
      inhibitor), potentiation with mianserin, lithium potentiation, ECT. The 87
      depressive patients had a median age of 79 and most had one or more severe
      somatic conditions. Fifty-nine were severely depressed at admission, 19 at
      discharge; the number of functionally disabled dropped from 22 to seven and the
      number of cognitively impaired from 35 to 19. In conclusion, a nihilistic
      approach to treatment in the very old is unfounded.

PMID- 9012056
TI  - [The demography of centenarians in Denmark].
AB  - The aim of this study was to describe the demography of centenarians in Denmark
      in the period 1775-1995. The prevalence of centenarians increased from about 1-2
      pr. million in the last half of the 1800s to about 80 pr. million in 1995,
      especially among women since 1950 leading to a female/male-ratio of three to one.
      A total of 4292 centenarian deaths were found reported in different sources. The
      number of reported centenarian deaths was found to be much higher in the first
      half than in the last half of the 1800s, especially among men and among 105+ year
      old: A through examination of 275 reported centenarian deaths on the Island of
      Funen from before 1900 indicates that this most plausibly was due to age
      exaggeration and lack of validation of the reported ages before 1850. This was
      supported by a backward extrapolation of regression estimates based on the
      reported number in the period 1870-1925, which showed a much lower estimated
      number of centenarians than reported in the first half of the 1800s, indicating
      an emergence of centenarians after 1780. The probability of becoming a
      centenarian only first increased substantially for cohorts born after 1860. The
      reduction of mortality among the oldest old in the last decades has created a new
      generation of very old people. The proportion of centenarians can therefore be
      considered as an indicator of earlier changes in lifestyle and care for elderly.

PMID- 9012057
TI  - [Centenarians in the county of Funen. Morbidity and functional capacity].
AB  - The aim was to examine the feasibility of a study of centenarians and to describe
      morbidity and functional capacity of centenarians in the County of Funen. A total
      of 51 out of 58 centenarians on Funen born on May 1, 1894 or before participated.
      An interview could be carried out almost completely in 80.4% of the 51
      participants, cognitive testing (MMSE) in 78.4% and physical performance test
      (PPT) in 49%. Additional information on morbidity and activities of daily living
      (ADL) was collected on all 51 centenarians from family members, nursing staff,
      GP's, hospital registries and the National Cancer Registry. Almost 3/4 were women
      and 58.8% were in an old people's home. Osteoarthrosis, urinary incontinence,
      heart failure, dizziness and eye diseases were found to be frequently prevalent,
      while hypertension, diabetes, cancer and stroke were found to be rare. Based on
      Katz' ADL index approx. 1/3 could be considered to be independent of help, while
      almost everybody was dependent on help for the instrumental activities (IADL). A
      low average score was found at the PPT, especially the walking speed was found to
      be very slow. Only 32.5% scored over 23 points at the MMSE, but allowing for
      severe impairment of vision and hearing more than 1/3 were found to be
      cognitively well-functioning. Severe dementia was found among 15.7%. Dependency
      on help for the ADL-functions was not found to be associated with health
      measurement, but strongly associated with visual function, PPT and MMSE (p <
      0.001). The characterization of centenarians as described in a number of foreign
      studies as being an homogeneous, relatively healthy and independent group could
      therefore not be confirmed. On the contrary, they were found to be very
      heterogeneous and characterized by multi-morbidity. By far the great part of them
      were in addition dependent on help in their activities of daily life. Approx.
      1/3, however, were found to be relatively independent of help for basic
      functions, more than 1/3 were cognitively well-functioning, and a very small
      number could even manage a few outdoor functions by themselves.

PMID- 9012059
TI  - [Utilization of antibiotics in Denmark 1994-1995. A population-based study].
AB  - The aim of this study was to explore the potential of individualized drug
      statistics to provide various epidemiological measures of the utilization of
      antibiotics. The data derive from the Register of Drug Statistics at the Danish
      National Board of Health. The most important measures were DDD/1000
      inhabitants/day, the number of patients and the distributions of prescriptions
      according to age and gender. The analysis encompassed 3,825,057 prescriptions
      presented by 1,670,801 patients during the period from 1 March 1994 to 31 May
      1995. The overall consumption was 12.1 DDD/1000 inhabitants/day. Sixty-two
      percent of all patients and 84% of the patients receiving sulfonamides were
      female. The most frequent drug used was V-penicillin which was prescribed to 48%
      of the patients. The group which consumed the greatest part of sulfonamides and
      quinolones were older women over the age of 65. It was concluded that the
      Register of Drug Statistics provides important information on individualized drug
      utilization.

PMID- 9012058
TI  - [Food consumption of the population. Trends followed via telephone interviews].
AB  - This study aimed at establishing and evaluating a simple method for surveilling
      trends in consumption of 10 nutritionally important foods. The method is based on
      food frequency questions combined with questions on the previous days intake,
      collected through telephone interviews. Participants (461 men, 546 women, 15-60+
      yrs) came from a population sample. Between 22 and 69% consumed the foods in
      question as frequently as prescribed by the Danish food recommendations (lowest
      for fish and for vegetables, highest for potatoes/rice/pasta). Characteristic sex
      and age differences were observed, similar to findings from traditional,
      quantitative food surveys in Denmark. The food frequency results were confirmed
      by results from the previous day's intake. Crossing of frequencies for different
      foods gave additional information on consumption patterns. The results indicate
      that this very simple method may be a useful supplement to traditional
      quantitative dietary surveys for surveilling trends in food consumption. The
      Danish Nutrition Council therefore aims at doing similar surveys every other
      year.

PMID- 9012060
TI  - [Contributing causes of malaria among Danish travellers].
AB  - A retrospective evaluation of contributing causes of malaria among Danish
      travellers, based on patient files and telephone interviews, is presented. Four
      centres participated, and 33% of all malaria cases reported to the Danish
      authorities in 1993 and 1994 were included (in total 82 patients). Ten out of 52
      patients with falciparum malaria had not taken any chemoprophylaxis at all. Among
      the 42 patients who had, only 14 were both correctly advised and fully compliant.
      Within the remaining 28 patients, lack of compliance concerning the
      chemoprophylaxis was reported in 16, inadequate chemoprophylaxis was prescribed
      to 12 patients, and a further eight (19%) were underdosed. Only four out of 30
      patients with vivax, ovale or malariae malaria had not used chemoprophylaxis. The
      distribution of contributing causes of chemoprophylaxis failure was similar to
      that of falciparum malaria, although noncompliance was more predominant in
      patients developing vivax, ovale or malariae malaria (58% compared to 38% in
      falciparum malaria).

PMID- 9012061
TI  - [Mortality among twins after the age of six: the programming hypothesis versus
      the twin-method].
AB  - According to the foetal-origins hypothesis the risk of adult morbidity and
      mortality is heightened by intrauterine growth retardation. Twins, and in
      particular monozygotic twins, experience growth retardation in utero. A total of
      8495 twin individuals born 1870-1900 in Denmark were followed through 1991 and
      death rates were calculated on a cohort basis. Deaths rates for twins and the
      general population were not significantly different except for females aged 60
      89: mortality for female twins in this age group was 1.14 times (SE 0.03) higher
      than the general population. Female dizygotic twins experienced death rates 1.77
      times (SE 0.18) higher than monozygotic twins at ages 30-59. Otherwise, mortality
      for monozygotic and dizygotic twins did not consistently differ after age six.
      The findings in the present study suggest that the foetal-origins hypothesis is
      not true for the intrauterine growth retardation experienced by twins.

PMID- 9012062
TI  - [Licorice. A basis for precautions one more time!].
AB  - A 38 year-old male was admitted to hospital with somnolence, flaccid paralysis of
      the extremities, arterial hypertension, oedema, severe hypokalemia and
      rabdomyolysis. The course was complicated with respiratory and kidney failure. It
      became apparent that the symptoms were caused by the ingestion of 200 g of
      licorice daily for ten weeks together with a thiazide diuretic for two weeks.

PMID- 9012063
TI  - [The promiscuous receptor].

PMID- 9012064
TI  - [The beginning of intensive therapy in Denmark].

PMID- 9012065
TI  - [Air pollution, disease and death].

PMID- 9012066
TI  - [Pneumococcal vaccination after splenectomy].

PMID- 9012067
TI  - [Evidence-based medicine--the same old story?].

PMID- 9012068
TI  - [Medical technology assessment--why now?].

PMID- 9012069
TI  - [The necessity of electronically updated meta-analyses: Doppler ultrasound in
      obstetrics as an example].

PMID- 9012070
TI  - [Treatment of refractory celiac disease].

PMID- 9012071
TI  - [Sedation and analgesia in ventilator-treated children].
AB  - Ventilator-treated children often require sedation in order to facilitate the
      ventilation. Sedatives alone or in combination with analgesics are commonly used
      for this purpose. In some cases, however, the addition of a neuromuscular
      blocking agent (NMB) may be necessary. In this article a survey is presented
      regarding both pharmacological and non-pharmacological means of improving the
      ventilator treatment in ventilated children. The most commonly employed
      sedatives, opioids and NMB's are discussed. The authors stress that whichever
      drug is used, it should be administered to the children guided by its effects
      rather than by a rigid scheme. In that respect monitoring of the treatment is
      important.

PMID- 9012072
TI  - [Diagnostic invasive procedures in the diagnosis of primary lung cancer.
      Diagnostic value and complications].
AB  - The invasive procedures used in the diagnosis of primary lung cancer are reviewed
      based on the literature. The choice of method should be related to its diagnostic
      accuracy, complications and cost. The chest x-ray provides the background for the
      further choice of diagnostic method. In central tumors, bronchoscopy meets the
      requirements and in peripheral lesions percutaneous transthoracic needle biopsy
      fulfils the conditions. In some centres, mediastinoscopy is preferred in all
      cases preoperatively, while others only perform this examination if a CT-scan
      shows mediastinal lymph nodes larger than 1 cm in diameter. If the latter
      procedure is followed, 10-30% of the patients will have lymph node metastases.
      Thoracoscopy is used when a pleural effusion remains undiagnosed after
      pleuracentesis. A considerable amount of patients will be shown to have pleural
      neoplastic spread even though cytological examination of the pleural fluid did
      not demonstrate malignant cells. The complication rates in all methods are low.

PMID- 9012073
TI  - [Low birth weight--increased risk of diabetic nephropathies?].
AB  - It has been demonstrated that intrauterine growth retardation gives rise to a
      reduction in nephron number. Oligonephropathy has been suggested to enhance the
      risk for expression of renal disease following exposure to potentially injurious
      renal stimuli. In a case-control study we investigated if low birth weight is a
      risk factor for development of diabetic nephropathy in 184 IDDM patients with
      diabetic nephropathy (persistent albuminuria > 300 mg/24 hours) and 182
      normoalbuminuric (< 30 mg/24 hours) patients. In women with birthweight < 10 th
      centile (< or = 2,700 g, n = 16) 75% had nephropathy compared to only 35% among
      patients > 90 th centile (> or = 4,000 g, n = 17) (p = 0.05). In men with birth
      weight < 10th centile (< or = 2,910 g, n = 22) the prevalence of nephropathy:
      50%, was similar to the prevalence among patients > 90th centile (> or = 4,200 g,
      n = 24) 54%. Mean weight at birth were similar in patients with and without
      diabetic nephropathy. Men with diabetic nephropathy were significantly shorter
      than men with normoalbuminuria (176.9 (7.1) vs 179.4 (6.5), p < 0.01). In
      conclusion, our study supports the hypothesis that genetic predisposition or
      factors operating in utero or early childhood, or both, contribute to the
      development of diabetic nephropathy.

PMID- 9012074
TI  - [Symptoms of urinary tract infections in general practice. A comparison of
      diagnostic criteria and treatment among general practitioners, microbiologists
      and urologists].
AB  - General practitioners' criteria for good clinical practice vary, and it is
      unknown whether systematic education by specialists could be expected to reduce
      variation. The aim of this was to describe general practitioners',
      microbiologists' and urologists' criteria for diagnosis, treatment, and follow-up
      of women with symptoms of urinary tract infection. Based on these examples,
      advantages and disadvantages of using specialists as consultants in GPs' peer
      group-based CME (continued medical education) are discussed. Three short case
      vignettes were presented in a questionnaire to GPs, microbiologists and
      urologists with prechosen choice of diagnostic, treatment, and follow-up
      strategy. A total of 154 (77%) GPs, 45 (51%) microbiologists, and 54 (61%)
      urologists answered the questionnaires. There was considerable variation in
      proposed strategy both within each specialty and between the specialties.
      Microbiologists, and to some extent urologists, would more often than the GPs
      treat a 30-year-old woman via telephone advice and prescription, while they more
      often tended to ask a 10- and 60-year-old woman to come to the clinic for
      examination. The GPs, more than the other doctor groups, would ask the patients
      to return for follow-up. Continuous medical education of GPs based on small-group
      peer discussions and with specialists as consultants in the groups cannot be
      expected to lead to less variation in choice of medical strategy.

PMID- 9012075
TI  - [Vaginal smears on clinical indication in a county with systematized screening].
AB  - In Denmark PAP-smear screening is performed by the GPs. The objective of this
      study is to report the proportion af smears taken on clinical indication over an
      eight week period in the county of Aarhus, and to obtain a precise reason for
      making a PAP-smear on clinical indication. Some 27% of all smears taken were on
      clinical indication. Some 55% of these smears were due to a follow-up on previous
      PAP-smears, while tests due to subjective symptoms account for the major part of
      the remaining tests. Testing the target group outside the screening programme is
      discouraged, but some 43% of tests on indication are not due to follow-up of
      previous smears. Further studies of the consequences of such testing are
      recommended.

PMID- 9012076
TI  - [Bilateral Achilles tendon rupture in individuals with renal transplantation].
AB  - Increased incidence of tendinitis and tendon ruptures is reported in recipients
      of a kidney transplant. Two cases of bilateral achilles tendon rupture after
      minimal trauma are described. Tendon ruptures are more frequent in individuals
      with kidney disease in dialysis or after transplantation compared with patients
      receiving other organ transplantations. It is therefore more likely that tendon
      ruptures are related to metabolic changes associated with kidney disease rather
      than with transplantation or with glucocorticoid treatment per se. Clinical
      symptoms of achilles tendinitis should be considered as warning signs prior to
      tendon rupture and treated appropriately to avoid further morbidity. There is no
      contraindication towards surgical suturing of an achilles tendon rupture in
      patients receiving immunosuppressive treatment including glucocorticoids.

PMID- 9012078
TI  - [On the response "The scientific basis for the assessment of medical
      technology"].

PMID- 9012077
TI  - [Respiratory syncytial virus: an important cause of influenza-like disese in the
      elderly].

PMID- 9012080
TI  - [The scientific basis for the assessment of medical technology].

PMID- 9012079
TI  - [On the response: "The scientific basis for the assessment of medical
      technology"].

PMID- 9012081
TI  - [Assessment of medical technology with command-ethics II].

PMID- 9012082
TI  - [The expert knowledge or the assessment of medical technology II?].

PMID- 9012083
TI  - [Scientific ethics and animal experiments].

PMID- 9012084
TI  - [The Gordian knot].

PMID- 9012085
TI  - [Public health--an old field with new perspectives].

PMID- 9012086
TI  - [Mycobacterium paratuberculosis--an etiological agent in Crohn disease?].

PMID- 9012087
TI  - [Enuresis nocturna--parents' and therepists' attitudes].
AB  - In a questionnaire study concerning voiding habits among seven year-old children
      starting school the prevalence of enuresis nocturna was 13.4% among girls and
      22.2% among boys. For 5.4% of girls and 8.2% of boys the symptom occurred at
      least once a week. Half of the children had secondary enuresis. Forty-six percent
      had consulted their doctor about the problem and 44% had received some kind of
      treatment. Ten percent had tried an alarm bell and 33% had tried desmopressin.

PMID- 9012088
TI  - [Arthroscopic subacromial decompression].
AB  - The aim of this prospective study was to evaluate the results of arthroscopic
      subacromial decompression (ASAD) in the treatment of impingement syndrome in
      patients without full thickness rotator cuff tears. Sixty patients (64 operative
      procedures) underwent ASAD during the study period; 37 men and 23 women, average
      age 46 years (range 28-63), average duration of symptoms 37 months (range 8-132).
      Patients with calcifying tendintis were not included. Evaluation preoperatively
      and one year postoperatively included: Constant score, clinical examination and
      radiological evaluation (supraspinatus outlet view). All follow-up examinations
      were done by an independent observer. Fifty-six patients (60 procedures) were
      available for follow-up. The average length of follow-up was 13 months (range 10
      23). Forty-six patients (77%) achieved a good or excellent result according to
      Constant score criteria. Preoperatively twenty-four patients had applied for
      worker's compensation benefits (WCB). Only half of the patients in the WCB group
      achieved a satisfactory result, whereas 94% of the non-WCB patients had a good or
      an excellent result. Arthroscopic subacromial decompression is an effective
      procedure for the majority of patients with stage II impingement syndrome. In
      this study WCB claims were associated with inferior results.

PMID- 9012089
TI  - [Are low back pain and radiological changes during puberty risk factors for low
      back pain in adult age? A 25-year prospective cohort study of 640 school
      children].
AB  - Recent reports have stated that low back pain (LBP) among children is a common
      problem comparable with that in adults. This 25-year prospective cohort study
      confirms that 11% of the cohort have had a history of LBP in adolescence with an
      84% lifetime prevalence of LBP in these subjects as adults compared with 70% in
      the rest of the cohort. LBP was associated with increased morbidity and decreased
      working capacity. Thirteen percent of the cohort had radiological abnormalities,
      mainly Scheuermann changes, in the thoracic and lumbar spine as adolescents, with
      no positive correlation to LBP in this period. Unlike other reports our results
      did not show any association between X-ray changes in the lower spine in
      adolescents and a higher prevalence of LBP in adults. Stepwise logistic
      regression analyses showed that LBP in the growth period and familial occurrence
      of back disease are important risk factors for LBP later in life, with an
      observed probability of 88% if both factors are present. Preventive measures in
      the school period seem to be of great importance.

PMID- 9012090
TI  - [The long-term prognosis of patients with acute chest pain of various origins].
AB  - A total of 204 patients with acute chest pain, but without myocardial infarction
      (non-AMI) were included. In 56 a definite diagnosis was obtained within 24-48
      hours of admission. The remaining 148 patients underwent a comprehensive
      examination program. Ischaemic heart disease (IHD) was diagnosed in 64 patients,
      81 had gastro-oesophageal disorders, 58 chest wall disorders, nine pericarditis,
      five pulmonary embolism, four pneumonia/pleuritis, three pulmonary cancer, two
      dissecting aortic aneurysm, one aortic stenosis and one herpes zoster. During 33
      months of follow-up, 31 of the 64 patients with IHD had a cardiac event (cardiac
      deaths, non-fatal AMI, bypass surgery or PTCA) whereas only three events occurred
      among the 140 patients without IHD (p < 0.00001). However, the frequency of
      readmissions and of recurrent episodes of chest pain were similar in the three
      major diagnostic groups (NS). It is concluded that the high risk subset of a non
      AMI population can be identified by means of non-invasive cardiac examination.
      The remainder who have other diagnoses are at low risk. However, the morbidity is
      high with frequent readmissions and recurrent episodes of chest pain, and the
      need for development of strategies with regard to diagnosis and treatment of
      these patients is emphasized.

PMID- 9012091
TI  - [Allergen decontamination and public sector].
AB  - Reduction of allergen exposure is one way to reduce exacerbations in allergic
      asthma. According to Danish legislation, the local authorities have to support
      initiatives which can reduce clinically relevant inhouse allergen exposure. A
      case of grotesque bureaucracy and ignorance of basic allergological facts is
      presented. Local administration confused allergy to cat dander with allergy to
      house dust mite and two appeal boards only reviewed legal aspects, not medical.
      After inquiry by the ombudsman, the case was reviewed by one appeal board and the
      patient was granted help. After three years the patient had moved to another
      district and the case was started all over again. It is recommended that direct
      contact between physicians should be preferred, in order to avoid
      misinterpretation of specialist statements. Original documents should always be
      requested to avoid transcription errors. Local public administration should
      respect legislation and improve the quality of their medical advisors.

PMID- 9012092
TI  - [Antidepressive agents in the treatment of obsessive-compulsive disorder].

PMID- 9012093
TI  - [To measure the unmeasurable].

PMID- 9012094
TI  - [Errors of the not-known?].

PMID- 9012095
TI  - [Public health in the socialized medicine state].

PMID- 9012096
TI  - [New physician reimbursement guidelines and private health insurance. I. Changes
      in general liquidation regulations].
AB  - In Germany, physicians' charges for the treatment of private patients have to be
      based on a fee-for-service schedule that is established by law. Every few years
      medical progress and changes of economic and legal conditions require major
      amendments. The latest adjustment reduces the accounts for laboratory tests and
      advanced imaging techniques. Further regulations concern the better information
      of patients about treatment costs and a reduced upper limit of fees for in
      patient procedures not performed by the head of the department himself. For
      private insurers it is a challenge to identify the quite frequent medical
      accounts which are not in accordance with the complex fee schedule.

PMID- 9012097
TI  - [Prognostic aspects of metabolic syndrome. Is the "good living" syndrome regarded
      seriously enough in general insurance medicine practice?].
AB  - Metabolic syndrome is characterized by a large number of metabolic disorders, the
      findings being generally a combination of insulin resistance, obesity,
      hypertension, dislipidemia and pathological glucose tolerance or diabetes
      mellitus type II. Metabolic syndrome is diagnosed too seldom in view of the fact
      that a prevalence of at least 10% must be assumed for the population as a whole.
      Besides genetic predisposition, environmental factors such as diet, physical
      inactivity and nicotine and alcohol consumption play a decisive role in its
      clinical manifestation. The paper briefly examines the pathophysiological
      connections between the individual findings, with the central role of insulin
      resistance being emphasized. With a multifactorial therapy, in which non
      medicamentous treatment is predominant, it must be assumed that on the whole
      compliance will tend to be poor. Prognostically the syndrome is serious, very
      frequently resulting in premature atherosclerosis. The paper concludes with a
      consideration of the underwriting of metabolic syndrome, one of the points being
      that the extramortality rates of the individual impairments should not be applied
      additively.

PMID- 9012098
TI  - [Sick building syndrome].
AB  - If within a group of people in a building or inner rooms non-specific health
      symptoms that diminish or vanish when the person is leaving the room are
      diagnosed, we call it Sick-Building-Syndrome (SBS). Physical, chemical,
      biological and psychological factors are held responsible for causing SBS.
      Generally, the non-specific health syndromes are not regarded as disease-causers
      although employees definitely suffer from these syndromes. It is characteristic
      for SBS that neither chemical-toxicological measurings of harmful substances in
      the air of inner rooms nor measurings of said substances concerning the
      biological material show any results that prove a health damage. Especially
      people employed at video display unit have to face a considerable strain on their
      health which is individually and interindividually rated and borne. If SBS occurs
      in the field of work the problems that come with it have to be taken seriously.
      Physicians and technicians have to analyse the problem and eliminate the
      deficiencies connected herewith. Generally the well-being concerning the
      physical, intellectual and psychological area desired by employees can be
      restored--and the Sick-Building-Syndrome can be cured. This is a very long and
      difficult procedure. Chronic courses of the SBS do not occur very often. SBS
      cannot be accepted as an occupational disease.

PMID- 9012099
TI  - [Multiple chemical sensitivity (MCS)--the so-called chemical multiple
      hypersensitivity].
AB  - Multiple chemical sensitivity syndrome (MCS) is believed to be a multiple organ
      disease caused by low-level exposure to chemical substances. It is characterized
      by central-nervous, gastrointestinal and irritative mucocutaneous symptoms. This
      phenomenon is not recognized in traditional medicine, opponents of the theory of
      a separate disease attributing all symptoms to psychopathological processes.
      Since this phenomenon is becoming increasingly prevalent in Western countries,
      appropriate strategies for its study need to be developed.

PMID- 9012100
TI  - [Unconventional concepts in environmental medicine].
AB  - More and more people are convinced to be afflicted with diseases caused by ill
      defined environmental factors. Until now it has also not been possible to
      delineate unambiguously common features to describe a syndrome-like pattern which
      is the essential requirement for rational prophylactic and therapeutic
      intervention. Despite of this scientific status a wide variety of supposedly
      diagnostic and therapeutic methods of unproven efficacy is currently advertised
      and often applied in a polypragmatic manner. Besides providing a description of
      the different techniques their clinical relevance is critically evaluated.

PMID- 9012101
TI  - [Comment on H. F. Brettel, B. Schmitt: Limiting costs of implantable
      defibrillators].

PMID- 9012102
TI  - Open peritoneal drainage in horses with experimentally induced peritonitis.
AB  - Peritonitis was induced in 12 horses by median celiotomy and 1 hour of small
      intestinal ischemia. Six horses had primary closure of the incision, whereas six
      horses had a plastic mesh sutured to the ventral abdominal wall leaving the
      abdomen open for ventral drainage. The mesh was removed after 5 days and the
      abdominal wall was closed by apposition of the linea alba and subcutaneous
      tissues and approximation ef the skin edges. Peritoneal fluid was collected and
      analyzed for nucleated cell count and total protein concentration on days 0 and
      5. Serum biochemical profiles, serum electrolyte concentrations, and complete
      blood counts were performed on days 0, 1, 2, 5, 6, 10, and 14. Body weight,
      rectal temperature, and physical examination findings were recorded daily for 30
      days, then horses were euthanatized and the abdominal cavity was examined for the
      presence of adhesions. Histological examination was performed to assess the
      inflammatory response of the healing body wall; inflammation scores were
      significantly lower in horses that had primary closure of the incision. The mesh
      was well tolerated by all horses and allowed egress of peritoneal fluid for 5
      days. Adhesions were present in four control horses and in two horses that had
      open peritoneal drainage. All horses that had open drainage developed incisional
      infections after mesh removal. Abdominal wall herniation did not occur in any of
      the horses. The mild peritonitis induced in this study was insufficient to
      establish the efficacy of open peritoneal drainage for an established peritonitis
      in horses; however, the results of this study indicate that open peritoneal
      drainage is feasible in horses.

PMID- 9012103
TI  - Detection of bacteria in equine synovial fluid by use of the polymerase chain
      reaction.
AB  - Equine synovial fluid aliquots were inoculated with Salmonella enteritidis,
      Escherichia coli, Actinobacillus equuli, Staphylococcus aureus, and Streptococcus
      zooepidemicus to obtain approximate concentrations of 1000, 100, 10, and 1 colony
      forming U/mL. Synovial fluid aliquots were also inoculated with an unquantitated
      inoculum of Bacteroides fragilis and Clostridium perfringens. Inoculated synovial
      fluid was incubated in trypticase-soy broth or Columbia broth for approximately
      12 hours. Then aliquots were removed for DNA extraction and polymerase chain
      reaction (PCR) analysis for detection of a 531 base-pair segment of bacterial DNA
      corresponding to a region of the 16S ribosomal gene. Duplicate samples of
      inoculated synovial fluid were prepared for microbial culture. Bacteria were
      detected in all samples inoculated with bacteria but not in control synovial
      fluid samples. Under experimental conditions there was no difference between
      microbial culture and PCR analyses for detection of bacteria. Experimentally, PCR
      was able to detect bacteria in synovial fluid within 24 hours of inoculation.

PMID- 9012104
TI  - Metacarpophalangeal joint synovial pad fibrotic proliferation in 63 horses.
AB  - Medical records, radiographs, and sonograms of 63 horses with metacarpophalangeal
      joint synovial pad proliferation were examined retrospectively. All horses had
      lameness, joint effusion, or both signs associated with one or both
      metacarpophalangeal joints. Bony remodeling and concavity of the distodorsal
      aspect of the third metacarpal bone (Mc3) just proximal to the metacarpal
      condyles was identified by radiography in 71 joints (93%); 24 joints (32%) had
      radiographic evidence of a chip fracture located at the proximal dorsal aspect of
      the proximal phalanx. Fifty-four joints (71%) were examined by ultrasound. The
      mean +/- SD sagittal thickness of the synovial pad was 11.3 +/- 2.8 mm. Seventy
      nine percent of the horses had single joint involvement with equal distribution,
      between the right and left forelimbs. Sixty-eight joints in 55 horses were
      treated by arthroscopic surgery. Sixty joints (88%) had debridement of chondral
      or osteochondral fragmentation from the dorsal surface of Mc3 beneath the
      synovial pad and 30 joints (44%) had a bone chip fracture removed from the medial
      or lateral proximal dorsal eminence of the proximal phalanx. Complete or partial
      excision of both medial and lateral synovial pads was completed in 42 joints.
      Only the medial synovial pad was excised or trimmed in 21 joints, and 5 joints
      had only the lateral pad removed. Eight joints in eight horses were treated by
      stall rest, administration of intra-articular medication and systemic
      nonsteroidal anti-inflammatory drugs. Follow-up information was obtained for 50
      horses treated surgically and for eight horses treated medically. Forty-three
      (86%) that had surgery returned to racing; 34 (68%) raced at an equivalent or
      better level than before surgery. Three (38%) of the medically treated horses
      returned to racing; only one horse raced better than the preinjury level. Horses
      that returned to racing at a similar or equal level of performance were
      significantly younger in age than horses returning at a lower level or not racing
      (P < or = .05). Overall, horses with synovial pad proliferation treated by
      arthroscopic surgery had a good prognosis for return to racing at a level equal
      or better than before injury.

PMID- 9012105
TI  - Application of a hook plate for management of equine ulnar fractures.
AB  - Closed fractures of the proximal aspect of the ulna were repaired in 10 horses
      younger than or equal to 6 months of age by application of a hook plate using a
      tension band principle. Ulnar fractures were classified as type 1A (2 horses),
      type 1B (4 horses), type 2 (1 horse), type 3 (1 horse), and type 4 (2 horses);
      all fractures had displacement of a proximal fragment. Complications were implant
      deformation (4 horses), screw pullout (1 horse), osseous sequestration (1 horse),
      ulnar fracture through a hole used to apply a tension device (1 horse), and
      metacarpophalangeal deformity associated with a displaced anconeal fragment (1
      horse). Hook deformation was likely associated with failure to insert screws in
      all of the proximal holes of the plate and also in two horses, possibly with
      difficult recovery from anesthesia. Seven horses were discharged from the
      hospital and were being used for athletic activities. Insertion of the hook
      through the tendon of the triceps muscle and incorporation of the fragment within
      the hook can be used to effectively reduce and stabilize a fragment that might
      otherwise not hold screws.

PMID- 9012106
TI  - A mechanical evaluation of the resistance of various interfragmentary wire
      configurations to torsion.
AB  - Fourteen interfragmentary orthopedic wire configurations were tested in torsion
      using a transverse fracture polyvinylchloride pipe model. These models included
      single and double Kirschner pins with and without orthopedic wire added to the
      configuration. The orthopedic wire was applied in either an encircling, figure-of
      eight (skewer pin), or cruciate pattern. Double Kirschner pins were applied in a
      mono- or biplanar fashion. An external fixator model was also tested. Stiffness,
      yield load, safe load, and energy of absorption were measured and calculated for
      each model. Orthopedic wire added to any configuration increased stiffness. All
      single pin configurations with orthopedic wire and the external fixator had the
      highest stiffness. Two Kirschner pins had a higher torsional yield load and safe
      load than single pin configurations with or without orthopedic wire. The external
      fixator model had the highest torsional yield load, safe load and energy of
      absorption of all configurations tested. However, the external fixator was only
      significantly different in safe load from the 900 biplanar configurations with
      wire and the cross pin configuration with encircling wire. The 900 biplanar
      configurations with wire and the cross pin configuration with encircling wire
      were equally as effective as the external fixator model in yield load and energy
      of absorption.

PMID- 9012107
TI  - A comparison of laparoscopic and belt-loop gastropexy in dogs.
AB  - A simplified technique for laparoscopic gastropexy (group 1) was compared to belt
      loop gastropexy (group 2) in eight adult male dogs randomly divided into two
      groups of four dogs each. Our hypothesis was that a satisfactory laparoscopic
      gastropexy would approximate the strength and operative time required for belt
      loop gastropexy. Operative time, surgical complications, postoperative morbidity,
      gross and histological appearance, radiographic microvascularization, and maximal
      tensile strength were measured and compared between the two groups. All dogs
      recovered from surgery. No morbidity was associated with either procedure. The
      mean (+/- SD) duration of surgery was 69.75 +/- 7.23 minutes for group 1 and
      58.75 +/- 7.63 minutes for group 2. Fifty days after surgery, the microvascular
      appearance of the gastropexy site was similar for both groups. Blood vessels were
      observed within each seromuscular flap but vascular ingrowth to the abdominal
      musculature was observed in only two dogs, one from each group. The maximum
      tensile strength at 50 days was 76.55 +/- 22.78 for group 1 and 109.21 +/- 22.29
      N for group 2. Differences between surgical duration and maximum tensile strength
      were not statistically significant (P > .05). Histologically, all gastropexies
      consisted of an adhesion composed of dense fibrous connective tissue. The results
      of this study indicate that laparoscopic gastropexy provides a minimally invasive
      alternative to open abdominal prophylactic gastropexy in dogs.

PMID- 9012108
TI  - Postcaval thrombosis and delayed shunt migration after pleuro-peritoneal venous
      shunting for concurrent chylothorax and chylous ascites in a dog.
AB  - Simultaneous chylothorax and chylous ascites related to intestinal
      lymphangiectasia was diagnosed in a 4-year-old spayed female dog. Palliative
      pleural and peritoneal drainage was accomplished by placement of fenestrated
      silastic sheeting into surgically created diaphragmatic defects, and implantation
      of a pleuro-peritoneal venous shunt. The immediate postoperative period was
      complicated by acute renal failure secondary to postcaval thrombosis originating
      at the site of placement of the efferent pump catheter and extending to the level
      of the renal veins. Rapid resolution of this complication was accomplished with
      systemic anticoagulation. Clinical signs related to fluid accumulation resolved
      for 10 weeks after which acute decompensation occurred and the dog was
      euthanatized. Postmortem examination showed that reaccumulation of fluid was
      associated with migration of the efferent limb of the shunt from the caudal vena
      cava.

PMID- 9012109
TI  - Comparisons of sevoflurane, isoflurane, and halothane anesthesia in spontaneously
      breathing cats.
AB  - The clinical effects of sevoflurane, isoflurane, and halothane anesthesia with or
      without nitrous oxide, were compared in healthy, premedicated cats breathing
      spontaneously during 90 minutes of anesthesia. The effect of nitrous oxide in
      accelerating the induction of and recovery from anesthesia was more evident for
      halothane than for sevoflurane or isoflurane. The cats recovered more rapidly
      from sevoflurane-oxygen than from either halothane- or isoflurane-oxygen. Heart
      rates did not significantly change during anesthesia with any of the anesthetics.
      Arterial blood pressures during sevoflurane-oxygen anesthesia were somewhat
      higher than those with either isoflurane- or halothane-oxygen. There were no
      significant differences in arterial blood pressures among sevoflurane,
      isoflurane, and halothane anesthesia when combined with nitrous oxide. The
      respiration rate during sevoflurane-oxygen was similar to that during halothane
      oxygen. There were no significant differences in respiration rate among
      sevoflurane, isoflurane, and halothane anesthesia when combined with nitrous
      oxide. The degree of hypercapnia and acidosis during sevoflurane anesthesia was
      similar to that observed during isoflurane anesthesia and less than during
      halothane anesthesia. The three anesthetic regimens, with or without nitrous
      oxide, induced a similar degree of hyperglycemia and hemodilution during
      anesthesia. Serum biochemical examination did not reveal any hepatic or renal
      injuries after each anesthesia.

PMID- 9012110
TI  - Influence of vaporizer setting on mask induction of dogs with isoflurane using an
      in-circuit vaporizer.
AB  - The speed of mask induction using an in-circuit vaporizer may be influenced by
      vaporizer setting. To investigate this in clinical patients, 18 dogs were
      randomly assigned to one of three groups. Each dog was premedicated and then mask
      induced with isoflurane using a Stephen's in-circuit vaporizer set at 1/2, 3/4,
      or full ON. We determined inspired isoflurane and oxygen concentrations at the
      level of the mask, respiratory rate, resistance to mask induction, and time to
      intubation. No significant differences were found between groups in resistance to
      induction or in time to intubation. At settings of 3/4 and full ON, inspired
      isoflurane concentrations at time of intubation ranged from 3.3% to 8.25%, and
      were significantly higher than those resulting from the 1/2 setting (range 2.1%
      to 4.6%). We conclude that it may be preferable to avoid settings greater than
      1/2 when using the Stephen's vaporizer for mask induction because of the
      potential adverse effects of high inspired inhalant anesthetic concentrations. In
      addition, use of higher vaporizer settings may not significantly speed induction.

PMID- 9012111
TI  - Differences in quantitated electroencephalographic variables during surgical
      stimulation of horses anesthetized with isoflurane.
AB  - The effects of noxious surgical stimulation on the electroencephalogram (EEG) in
      15 horses anesthetized with isoflurane were evaluated during orthopedic (group 1)
      and soft tissue (group 2) procedures. The quantitative EEG variables theta/delta
      ratio (T/D), alpha/delta ratio (A/D), beta/delta ratio (B/D), median power
      frequency (MED), and 80% spectral edge frequency (SEF 80) recorded during
      Surgeries at 1.7% end-tidal concentration of isoflurane (ET(iso)) were compared
      with values from five nonstimulated control horses anesthetized at 1,7% ET(iso).
      The EEG variables T/D, A/D, MED, and SEF 80 from surgically stimulated horses
      were significantly higher compared with controls. These differences in measured
      EEG variables were accompanied by a significantly lower relative power in the
      delta frequency band and a concomitant significantly higher alpha activity.
      Because the A/D ratio, MED, and SEF 80 in surgically stimulated horses were
      significantly higher than in nonstimulated control horses these measured EEG
      variables may provide a valuable tool for identification of nociceptive
      transmission in isoflurane anesthetized horses.

PMID- 9012112
TI  - Experiences with morphine injected into the subarachnoid space in sheep.
AB  - The effects of morphine (M), 0.1 mg/kg, administered into the lumbosacral
      subarachnoid space of sheep used for experimental stifle surgery, were
      investigated. In a pilot study, preservative-free morphine was administered to
      three sheep, morphine containing preservatives to two sheep, and saline (S) to
      one sheep. After recovery from anesthesia, all five sheep administered M
      displayed rear limb weakness. One sheep, which had received morphine containing
      preservatives, also licked and chewed incessantly at its flank and hindquarters
      during recovery. A group of 24 sheep was used to study the effects of morphine
      containing preservatives, injected intrathecally, on recovery from general
      anesthesia and hindlimb orthopedic surgery. Eight sheep received M, eight sheep
      received S, and eight sheep had a needle placed in the subarachnoid space without
      any injection (N). Times from end of anesthesia to standing varied greatly and
      did not differ significantly among groups (P = .73), with M sheep averaging 119
      minutes; S sheep, 87 minutes; and N sheep, 83 minutes. One sheep administered M
      licked and chewed at its hindquarters during recovery. Another group of 24 sheep
      was used to study the effects of morphine containing preservatives, injected
      intrathecally, on postoperative lameness. Treatments were as described
      previously. Sheep were videotaped intermittently for 36 hours after surgery, and
      each sheep was scored as follows: 0 = not lame; 1 = slightly lame; and 2 = very
      lame. The average lameness scores, which did not differ significantly among
      groups (P = .21), were: M sheep, 1.07; S sheep, 0.81; and N sheep, 0.68. One
      sheep administered M displayed extensor spasms of the hindlimbs, and could not
      stand until several hours after surgery. We conclude that subarachnoid morphine
      at the dosage used produces no apparent benefit in sheep which have had stifle
      surgery, and in fact may cause detrimental side effects, such as hindlimb
      weakness, and pruritus or irritation of the hindquarters.

PMID- 9012113
TI  - [Extra-thyroid autoantibodies in autoimmune thyroiditis].
AB  - Organ specific autoimmune diseases do not occur isolated. In the authors group of
      4509 patients with confirmed autoimmune thyroiditis the authors investigated the
      frequency of extrathyroid organ specific and non-specific autoantibodies. The
      objective was to draw attention to other autoimmune diseases which may not yet be
      clinically manifest. The mutual positivity of antibodies against thyroid
      peroxidase (TPO) and antibodies against the adrenals was: in the zona glomerulosa
      21.1%, in the zona fasciculata 3.0%, in the zona reticularis 19.5%, in the
      adrenal medulla 9.0%. The mutual positivity of antibodies against TPO and ovaries
      was 28.5%, testes 12.5%, parathyroid 10.2%, islets of Langerhans 8.2%, hair
      follicles 45.0%, cell nuclei 26.1%, mitochondria 3.1%, smooth muscles 2.4%,
      striated muscle 0.2%, and gastroparietal cells of the stomach 12.3%. These
      results draw attention to the importance of polyclonal activation of the
      autoimmune process in endocrinopathies and the necessity to assess extrathyroid
      autoantibodies in autoimmune thyroiditis.

PMID- 9012114
TI  - [Status and selenium intake as related to the thyroid gland in the population of
      Znojmo].
AB  - In a group of 360 people aged 6-65 years of both sexes from the Znojmo area the
      author investigated the selenium status and intake by serum analyses (246 cases),
      urine analyses (356 cases) and hair analyses (28 analyses in middle-aged men). By
      correlation analysis the author investigated the relationship of selenium and
      metabolic and peripheral thyroid parameters. From the low selenium concentration
      in all investigated materials (42 micrograms Se/l serum, 8.2 micrograms Se/urine,
      7.2 micrograms Se/g creatinine in urine and 0.23 microgram Se/g hair) the author
      concludes that there is selenium deficiency in the investigated population, the
      primary cause being a low dietary selenium intake (average adult intake 17 to 25
      micrograms Se/day). From significant, though loose correlations between selenium
      concentrations and thyroid parameters (size, texture, number of nodes), serum
      concentrations of thyroid hormones (and their ratios resp.), as well peripheral
      parameters of hormone actions (Achilles tendon reflex, pulse rate or
      anthropometric variables) the conclusion is drawn that the selenium deficiency is
      so marked that it interferes in the investigated population with the regulation
      of the organism by thyroid hormones. This effect may be caused by changes of
      hormone formation in the thyroid gland due to the concentration of Se-dependent
      peroxidase, but in particular changes of their metabolism in the circulation and
      periphery, as selenium participates in the active centre of deiodase I in the
      formation of metabolically active triiodothyronine, and selenium deficiency has
      an impact also on deiodase II activity in some specialized tissues.

PMID- 9012115
TI  - [Changes in urinary calcium and magnesium levels during supplementation with
      iodine and selenium].
AB  - The authors examined 31 children aged 10-13 years before and after 5-month
      administration of 100 micrograms iodine (as iodide 100 Merck) and 57 university
      students (age 18-23 years) divided into four groups. The control group of 15
      students received placebo daily, 20 students took selenium (50 micrograms
      selenium Merck), 8 students iodine (100 micrograms iodide) and 14 students a
      combination of equal amounts of both elements. The authors investigated the
      calciuria, mangesiuria and calcium/creatinine ratio and magnesium/creatinine
      ratio. They found a significant drop of magnesiuria in school children after
      iodine intake, and in university students there was a significant drop of the
      magnesium/creatinine ratio in iodine and selenium treated groups as well as those
      who received a combination of both elements. In the latter group there was also a
      significant drop of the urinary calcium/creatinine ratio. The findings assembled
      in a relatively small group of children and students is considered preliminary.
      It suggests, however, the possible influence of supplementation with iodine and
      selenium in commonly used amounts on calcium and magnesium excretion. Changes in
      the control group may be due to seasonal influences.

PMID- 9012116
TI  - [Plasma and tissue levels of cytokines and adhesive molecules in patients before
      strumectomy].
AB  - From a group of 134 patients with complete documentation before goitrectomy the
      authors selected 10 histologically defined cases of (A) simple colloid nodular
      goitre, (B) toxic parenchymatous goitre type GB and (C) autoimmune thyroiditis.
      Marked hormonal suppression was achieved in group B by thyrostatic therapy, as
      compared with A and C, the autoantibody titres (TGAb and TMAb) differentiated the
      groups. The authors examined the interleukin 6 concentrations and those of its
      soluble receptor (IL-6, IL-6R), of the tumour necrotizing factor alpha (TNF
      alpha) interferon gamma (IFN-gamma) and of adhesion molecules ICAM-1 and VCAM-1.
      Plasma values were, except for not very significant differences, similar in all
      groups and ruled out a marked effect on tissue levels. The most remarkable
      finding in the homogenate of a peroperative excision were low IL-6, IL-6R and
      adhesion molecule values in group A, as compared with B and C and the absence of
      differences in TNF-alpha values between groups and in particular markedly higher
      IFN-gamma values in group B which supports theories on the etiopathogenetic role
      of this cytokine in GB disease. The pilot study is part of the preparation of in
      situ hybridization of mRNA for diagnostically usable cytokines.

PMID- 9012118
TI  - [Dermatoglyphics--an attempt to predict diabetes].
AB  - Dermatoglyphs do not change throughout life. The authors sought their "predictive
      type" for diabetes with regard to the possibility of early prediction and thus
      prevention of the development of diabetes, in particular type 2. They used a
      point score of the abnormality in three qualitative and two quantitative signs
      and found, as compared with the normal population, in groups of subjects with
      impaired glucose tolerance, DM II and DM I deviations with an increasing
      significance. The frequency of thus assessed abnormalities in each subject on
      both hands (0-10) was compared in relations to the diagnosis and family-history
      of diabetes and the authors evaluated the incidence of different abnormalities in
      the whole group of 300 subjects and in sub-groups. After statistical evaluation
      the authors conclude that the abnormality of the qualitative sign of the C line
      (lacking or reduced) could be considered as another early predictive factor: in
      the offsprings of diabetics for both types of diabetes, in the remainder for DM
      type 1.

PMID- 9012117
TI  - [Ret proto-oncogene mutation found in the Czech population and its predictive
      value for offspring of patients with medullary carcinoma of the thyroid gland].
AB  - The authors completed a total of 23 pedigrees with the clinical diagnosis of
      medullary thyroid carcinoma (5 MEN 2A pedigrees, 11 FMTC pedigrees and 7 MTC
      pedigrees). Using the method of polymerase chain reaction (PCR), it was possible
      to define the rate of the most frequent mutations in exons 10, 11 and 16 of Ret
      protooncogene present in the Czech population. The most frequent hereditary
      mutation found in MEN 2A and FMTC groups is substitution of thymine for cytosine
      in position 2095 of the transmembranous domain of the Ret-tyrosine kinase gene.
      Another six types of known mutations were tested.

PMID- 9012119
TI  - [Non-insulin-dependent diabetes mellitus--strategies and problems in genetic
      research].
AB  - Non-insulin dependent diabetes mellitus (NIDDM) is at present one of the most
      serious and widespread diseases with a mass incidence and its treatment is very
      costly. In the genesis and development of the disease genetic factors participate
      along with environmental factors. Genetic research of NIDDM is difficult, as
      ensues from the very essence of this heterogeneous disease. Research concentrates
      on the identification of specific genetic determinants which influence the
      predisposition of the individual to glucose intolerance which, if revealed, would
      make more effective prevention and treatment possible. Intensive research is
      focused on different candidate genes. Although some "minority" genes were
      identified, the primary diabetogen was not revealed so far and partial positive
      results must be confirmed on a larger population sample. The article reviews the
      contemporary state of genetic research of the disease.

PMID- 9012120
TI  - [Thyroglobulin and microsome autoantibodies and their clinical significance in
      adult type I diabetics].
AB  - In 34 patients with type 1 diabetes manifested in postadolescent age (mean age at
      time of diagnosis 25 years, 18 women and 16 men) after the establishment of the
      diagnosis perspectively the presence of antibodies against thyroglobulin and the
      microsomal fraction and their relation to affection of the thyroid gland was
      investigated. During an investigation of 20% of the patients the authors provided
      repeatedly evidence of the presence of both antibodies, in 23% repeatedly only
      against microsomes. In 21% some antibodies were detected only once. In the course
      of the investigation in 65% of the patients thyroid antibodies were found. The
      clinically most serious affection of the thyroid gland (from the sonographic an
      functional aspect) was found in groups 1 an 2, while in groups 3 and 4 in the
      majority of patients the thyroid gland was not affected. A different pathogenesis
      of the disease in the above groups is suggested in the areas of DR and DQ during
      HLA typing, the behaviour of other antibodies and differences in dermatoglyphic
      examinations. Moreover there is a high ratio of women in the first two groups
      (61%) and conversely of men in groups 3 and 4. In the discussion attention is
      drawn to the different course of diabetes in patients with thyroid autoimmunity.

PMID- 9012121
TI  - [The effect of metformin on lactate levels in type II diabetes].
AB  - The authors investigated the lactic acid levels in the blood of 57 type 2
      diabetics treated with metformin. The mean lactate level before onset of
      metformin treatment was in the whole group 2.01 +/- 0.36 mmol/l and after 6
      months of metformin administration it remained unchanged 2.00 +/- 0.42 mmol/l.
      Compensation of diabetes evaluated by HbAlc improved significantly (9.74 +/-
      1.62% before treatment, and 8.52 +/- 1.36% after 6 months of treatment). The mean
      cholesterol levels declined significantly and the mean triacylglycerol levels
      were after two months of metformin administration significantly lower. Metformin
      treatment did not lead to an increase of the patients body weight.

PMID- 9012122
TI  - [Hemostasis in patients with diabetes mellitus. II. Tissue factor and the
      extrinsic blood coagulation inhibitor].
AB  - In the submitted pilot study we examined 37 patients suffering from diabetes
      mellitus without vascular complications and 15 healthy blood donors. The diabetic
      patients had not, as compared with the blood donors, significantly elevated
      values of the tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The
      TFPI levels correlated with other markers of endothelial dysfunction, in
      particular thrombomodulin (r = 0.452, p < 0.01) and with triacylglycerol and
      cholesterol levels. They did not correlate with age, the C-peptide level and BMI.

PMID- 9012124
TI  - [The role of thromboxane in the pathogenesis of nephropathies].
AB  - Impaired haemostasis, in particular aggregation in renal disease stimulated
      research of its prevention and treatment. The achieved results are a significant
      contribution not only to theoretical research but also to its application in
      nephrological practice. The submitted review presents specific features of
      nephrological patients ensuing from overproduction of prostaglandins, in
      particular thromboxane, by renal cells, focused on glomeruli where mesangial and
      epithelial cells participate in prostaglandin production and where thromboxane is
      associated with hyperfiltrations, proliferation, aggregation and other processes
      damaging glomeruli.

PMID- 9012123
TI  - [Ablation of supraventricular tachydysrhythmias with direct and radiofrequency
      current].
AB  - Ablation therapy of tachycardias refractory to pharmaceutical preparations is
      considered in recent years the method of choice. In the submitted paper the
      authors give an account of 12 years experience with ablation treatment of
      supraventricular tachycardias. The group comprises 23 patients, who were
      subjected to ablation therapy by radiofrequency current (RF) on account of
      relapsing supraventricular dysrhythmias, resistant to medicamentous treatment
      (between May 1994 and February 1996). The mean age of the patients was 60.4 +/-
      9.2 years. The historical control group is formed by 13 patients who were
      subjected to ablation of the AV junction by direct current (DC) between March
      1984 and April 1994, their mean age being 68.4 +/- 10.4 years. After DC ablation
      the operation was successful in 8 cases (62%) where complete AV block was
      achieved, while it was partially successful in two cases where modification of
      the conductivity was achieved (15%) and it failed in three cases (23%). The
      levels of AST and CK enzymes at the investigated time intervals are significantly
      higher than in the RF method. During RF ablation the mean duration of successful
      ablation sequence was 36 s, the mean energy 1 042 +/- 726 J, the median number of
      sequences was 10.5. In ablation of the AV junction the success was 95%. In one of
      two patients who were subjected to ablation of arterial flutter a relapse of
      tachycardia was recorded after an interval of 24 hours. Subsequently complete
      ablation of the AV junction was performed. In a female patient with
      atrioventricular reciprocal tachycardia due to a latent accessory pathway in the
      area of the free left ventricular wall temporarily tachycardia could not be
      induced, however, after discharge from hospital the paroxysms of supraventricular
      tachycardia with a substantially lower frequency reappeared. Comparison of the
      two methods does not suggest a significant difference of their effectiveness, the
      RF method causes, however, less extensive myocardial damage.

PMID- 9012125
TI  - [Spontaneous ascites infections].
AB  - Spontaneous ascitic infection is a relatively frequent, serious and rarely
      diagnosed complication of cirrhotic ascitic. The author summarizes the
      classification of the disease and recommends to use term spontaneous ascitic
      infection instead of the narrower concept spontaneous bacterial peritonitis. He
      discusses the symptoms of the condition, its diagnosis and contemporary trends in
      treatment and prevention. He emphasizes in particular the necessity to consider
      this complication of cirrhosis, to diagnose it in time and treat it and thus to
      improve the prognosis of patients with cirrhosis and ascitic.

PMID- 9012126
TI  - [Prevention of thromboembolism in patients with atrial fibrillation].
AB  - Atrial fibrillation is a disorder of the cardiac rhythm associated with an
      increased risk of thromboembolism. Several studies in the past confirmed that
      anticoagulation or also antiaggregation therapy is associated in these patients
      with a reduced incidence of cerebrovascular attacks and peripheral embolism. For
      a more objective assessment of the risk of individual patients risk factors of
      thromboembolism in atrial fibrillation were defined. They include cardiac
      insufficiency, hypertension, a history of embolism, left atrial dilatation,
      systolic dysfunction of left ventricular hypertrophy and spontaneous echo
      contrast. This risk stratification of patients with atrial fibrillation is the
      basis for correct selection of subsequent treatment. In patients without risk
      factors treatment with acetylsalicylic acid can be recommended, if older than 60
      years. In younger patients no treatment is necessary for prevention of
      thromboembolism in this group. In the presence of one or several risk factors
      permanent anticoagulation treatment with a target value of INR 2.5 is necessary.
      In patients with atrial fibrillation associated with a congenital or acquired
      heart disease warfarin is administered with a target value of INR 3-4. The same
      approach is used in patients with chronic and paroxysmal atrial fibrillation.

PMID- 9012127
TI  - [Education of diabetics. Recommendations of the Czech Diabetology Society].

PMID- 9012128
TI  - [Basic indicators characterizing the acid-base equilibrium in the body and its
      disorders].

PMID- 9012129
TI  - [Dosage of ACE inhibitors in heart failure].

PMID- 9012130
TI  - [Role of host behavior in the life cycle of parasites].
AB  - Parasite is an organism which, at least in a part of its ontogeny uses another
      living organism as a proper environment for its life. In the "parasite-host"
      relationships, formed by both these components, the parasite itself bears the
      burden of formation and maintenance of these relationships in a balance. Three
      factors play the main role in this process: (1) physiological adaptations of the
      parasite, enabling survival in the host body and resistance against defence
      reactions of the host; (2) morphological adaptations, leading to changes in the
      body structure of the parasite, dependent on location in the host body; and (3)
      behavioural adaptations assuring contacts of parasites with their hosts. In the
      process of evolution most groups of parasites evolved a complicated life cycle,
      with change of host and outer environment, succeeding in maturation of the
      parasite and production of the offspring. To pursuit this aim the parasite takes
      advantage from the behaviour of its potential host, its food preferences (e.g. by
      inclusion into a food chain), periodic or circadian migrations, and generally
      from its mode of life. The parasite modifies behaviour of its hosts, sometimes to
      a high degree, especially the behaviour of intermediate hosts, making them more
      conspicuously displayed for predators, the most often their final hosts. The
      parasite itself changes also its behaviour to be more attractive for a potential
      host or to enhance the possibility of finding a proper host. Finally, in a host
      population the parasite bears upon the position of particular host individuals by
      degradation of dominants and shifting them from reproduction. This phenomenon may
      be considered as a self-defence of the host population against reproduction of
      ill individuals, weaken by a burden of parasites.

PMID- 9012131
TI  - [New details of the life cycle of Myxobolus cerebralis according to the
      literature].
AB  - The article comprises new details of the life cycle of Myxobolus cerebralis, the
      parasite of the skeleton of salmonids. Although this species has been known since
      1903, its complete life cycle has remained unknown till now or it has comprised
      mistaken details. Recently EL Matbouli et al. (1995) have described the life
      cycle of this parasite with numerous new data. M. cerebralis provokes in
      salmonids (especially in rainbow trouts) the whirling disease and heavy
      economical losses. Therefore the article may be useful for Polish
      ichthyopathologists. Besides the new description of the life cycle of M.
      cerebralis the authoress of the article gives her own considerations on some
      topics connected with this life cycle, which still remain insufficiently
      explained. The considerations concern the mechanism of the specificity of the
      invasive stages of the parasite to two species of its hosts (Tubifex tubifex and
      Oncorhynchus mykiss) and also to tissue specificity, the possibility of better
      and more effective control of whirling disease in breeding conditions through the
      knowledge of the complete life cycle of the parasite, the pathogenic activity of
      the parasite on fish central nervous system in spite of the lack of its lesions
      noted by EL Matbouli et al. (1995). The authoress pays attention to the necessity
      of future studies on the mitotic and meiotic cleavages of the developmental
      stages of the parasite. She considers also if the very complicated life cycle of
      M. cerebralis determined during the long evolution of this species may be
      recognized as favourable feature for it.

PMID- 9012133
TI  - [The effect of temperature on the infective activiey oncospheres of Diorchis
      stefanskii hymenolepididae].
AB  - Heterocypris incongruens (RAMD.) was selected as an intermediate host, having
      emerged as the main host for Diorchis stefanskii Czapl. in experimental
      conditions. It was found that the index of infective activity for larvae of D.
      stefanskii was high on the first day, amounting to 50-54%, with an extensity of
      infection of 100%. The infective activity of larvae declined slowly but steadily
      at the low temperature (5 degrees C). Oncospheres retained their infective
      activity for more than 2.5 months. In contrast, in culture at 18-20 degrees C and
      25 degrees C, the infective activity of larvae had declined rapidly only a few
      days into the experiment. The irrevocable loss of tapeworm infectivity occurred
      at temperatures of -5 degrees C and +38 degrees C, at which 100% of oncospheres
      died.

PMID- 9012132
TI  - [Strongyloidosis. II. Clinical manifestations].
AB  - Clinical manifestations of chronic, uncomplicated and severe, complicated
      disseminated strongyloidosis of a patient infected with Strongyloides stercoralis
      are shown. Cutaneous, gastrointestinal, hepatobiliary, pulmonary, rheumatic,
      neurological, psychiatric symptoms, as well as those of genitourinary, and
      cardiovascular systems and other clinical manifestations are discussed.

PMID- 9012134
TI  - [The effect of cydectin on the survival of second stage larvae and mature Ascaris
      suum cultured in vitro].
AB  - Larvae of Ascaris suum (L2) newly hatched from eggs with sodium hypochlorite,
      were placed (2000 larvae per 2 ml) of culture in EAGLE's medium, containing 10%
      calve serum or without it. Moxidectin (Cydectin) was introduced into medium in
      concentrations: 5, 10, 25 and 50 micrograms/ml. The cultures were incubated for 3
      days, and there were controlled every 12 hours. The effect of drug on survival of
      larvae was slightly expressed. After 3 days survival rates were 87, 81, 80 and
      78% in medium with serum, respectively to moxidectin concentrations. The
      lethality of larvae was higher in medium without serum, and amounted to 17, 23,
      29 and 31% in comparison with control probe after 72 hours. Adult Ascaris were
      placed on ARS medium with glucose (0.1%) containing moxidectin in concentrations
      1, 5, 50 and 100 micrograms/ml. The worms' condition was examined every day based
      on motility and turgor of their body. After 14 days of incubation in control
      probe 50% worms were alive, but their vitality was reduced. The behaviour of
      Ascaris in the presence of 50 micrograms/ml moxidectin was similar to those from
      the control. Only the highest concentration of drug (100 micrograms/ml) was
      lethal in 100% on the 8th day. The lower moxidectin concentrations (1 and 5
      micrograms/ml) were not lethal to adult worms, they had even the positive effect
      on survival rate and condition of adult Ascaris. The eggs laid by females which
      were maintained in culture with drug were collected. There were no disturbances
      in their future development.

PMID- 9012135
TI  - [Taeniasis in Wroclaw and Czestochowa provinces].
AB  - On the basis of control cards of taeniosis collected in the Sanitary
      Epidemiological Stations the comparison of the infectivity in 1980-1994 was
      carried out. Standard parameters environment (town, village), sex and age groups
      as well as morbidity rates/100,000 inhabitants were taken into consideration.
      Since 1980 the number of registered cases was reduced from 21.2 in Wroclaw urban
      populations and 15.5 in rural population as well as 6.3 in Czestochowa urban
      populations and 2.9 in rural population to 5.0 and 3.3 as well as 1.1 and 0.9,
      respectively in 1994. More frequent occurrences of taeniosis (6.7 mean morbidity)
      in Wroclaw than in Czestochowa province (1.4) were noted.

PMID- 9012136
TI  - [Observations on the vitality of lice from dead pigeons].
AB  - Experiments were carried out in July, September, October 1993 and January 1994 on
      48 dead pigeons kept in cold storage (refrigerating machine) and at a window. The
      behaviour of Mallophaga was observed. The insects left the feather after the
      cooling of the bird body, usually after 24 hours. The process lasted 3 days in
      cold storage conditions, while in outdoor (open-air) environment the Mallophaga
      were still alive for another 14 days. The vitality of Mallophaga is bigger in
      open-air, in moderately higher temperature and in warmer seasons of the year. The
      examined representants of three species dominating in infestation demonstrated
      varying suitability for survival in harder conditions. The reaction of
      Hohorstiella gigantea lata (PIAG.) to the drop of temperature was the fastest,
      while Columbicola columbae columbae (L.) reacted more slowly and the reaction of
      the Campanulotes bidentatus compar (BURM.) was the slowest. Also the reaction of
      larvae to falling temperatures was faster that that of the adult forms.

PMID- 9012137
TI  - [Further studies on parasitic arthropods of the elk Alces alces in Poland].
AB  - In the northeastern part of Poland, 239 elks (5% of the Polish population) were
      examined and 7 species of ectoparasites were found. The most frequent included:
      Lipoptena cervi (94%) and Chorioptes texanus is new species in Poland and it was
      noted at 50 sites from Warmia and the Mazurian Lake District.

PMID- 9012138
TI  - [Passive smoking].

PMID- 9012139
TI  - [Epidemiology of health problems caused by passive smoking].
AB  - Smoking has long been known to cause premature death and different illnesses.
      Each year 3 million people die from smoking related diseases worldwide. In recent
      years there has been concern that non-smokers may also be at risk for some of
      these adverse effects on health as a result of their exposure to tobacco smoke in
      various environments polluted by smokers. In 1986 the National Research Council
      and the Surgeon General of the U.S. Public Health Service independently assessed
      the health effects of exposure to environmental tobacco smoke (ETS). Both reports
      conclude that ETS can cause lung cancer in adult non-smokers and that children of
      parents who smoke have an increased frequency of respiratory symptoms and acute
      lower respiratory tract infections. The condition of asthmatic children improves
      significantly when they are removed from ETS. The most severe form of passive
      smoking is induced by smoking during pregnancy. The effects concern birth weight,
      complications of pregnancy and impaired development in childhood.

PMID- 9012140
TI  - [Passive smoking, a risk factor for lung carcinoma?].
AB  - The established elevated risk of lung cancer in smokers led to the hypothesis
      that environmental tobacco smoke (ETS) also causes malignancies. The solution of
      this question is complicated by low exposure levels and dose-response dependence,
      as well as threshold levels. The differences between the toxins in the main- and
      side-stream of tobacco smoke and also the lack of significantly elevated risk
      ratios in epidemiological studies do not permit scientific conclusions endorsing
      a connection between passive smoking and lung cancer, which has become an
      emotionalised issue.

PMID- 9012141
TI  - [Molecular biology of tobacco smoke associated neoplasia].
AB  - Adducts, formed by carcinogens of tobacco smoke with DNA, can be detected by
      means of molecular techniques and are used as marker of internal exposure.
      Carcinogen-DNA adducts produce specific mutations in tumor-suppressor genes (e.g.
      p53) and oncogenes (e.g. ras), which can be involved in tumor initiation or in
      later stages of tumor progression (e.g. evolution of an invasive phenotype).
      Benzo(a)-pyrene, an important carcinogen of tobacco smoke, induces GT
      transversions, as demonstrated in in vitro systems and animal models. Mutations
      in the p53- or ras-gene are more common in human tumors of the lung, head and
      neck, bladder and pancreas in smokers than in non-smokers. Molecular biology of
      cancer gains increasing significance in clinical practice since 1.) the presence
      of certain mutations confers an unfavorable prognosis to malignant disease (e.g.
      ras mutations in lung cancer), 2.) ras and p53 mutations often occur early during
      tumor development and can thus facilitate diagnosis of malignant disease, and 3.)
      minimal residual disease can be detected using molecular techniques. After
      resection of cancer of the head and neck, tumor recurred more frequently in
      patients with no evidence of residual disease as assessed by pathohistologic
      criteria than in patients with no evidence of residual disease as evaluated by
      p53 immunostaining.

PMID- 9012142
TI  - Passive smoking, platelet function and atherosclerosis.
AB  - Active smoking is a well known risk factor for the development of atherosclerosis
      and in particular coronary heart disease and peripheral vascular disease. The
      negative effects of active smoking demonstrated on platelet function, the
      eicosanoid system and platelet thromboxane A2 generation may contribute to the
      hemostatic imbalance reported. Recently, the problem of passive smoking as a
      health risk has been widely discussed. Detailed information on the role of
      passive smoking on hemostatic parameters, however, is still very limited. As far
      as present knowledge is concerned, platelet activation seems to be significantly
      involved in the deleterious vascular effects of passive smoking as well.

PMID- 9012143
TI  - [Single passive smoking exposure induces no measurable oxidation of low density
      lipoproteins].
AB  - Oxidation of low-density lipoproteins (LDL) is well known to increase the
      atherogenic risk. Active smoking has been claimed to be associated with a
      significant oxidant stress determined by enhanced LDL oxidation and isoprostane
      formation. We assessed the susceptibility of LDL to oxidation in 9 healthy non
      smokers and 7 smokers before and after three and five hours' exposure to passive
      smoking. Baseline values for the lag time, diene formation, malondialdehyde and
      isoprostanes differed in part significantly. In contrast to the data on active
      smoking, passive exposure to cigarette smoke did not significantly affect any of
      these parameters, nor diene formation and electrophoretic mobility in smokers and
      non-smokers alike. These results indicate that a single exposure to passive
      smoking does not induce relevant oxidation of LDL in men.

PMID- 9012144
TI  - [Diagnosis of thrombophilia--cui bono?].

PMID- 9012145
TI  - [Activated protein C resistance--an evaluation of current status].
AB  - The discovery of APC resistance and of the factor V Leiden mutation brought a
      break-through in thrombosis research and has greatly improved our understanding
      of the pathogenesis of venous thrombosis. In particular, it became obvious that
      thrombotic disease is the result of multiple factors. However, many clinically
      relevant questions still remain unanswered: for instance, the individual risk of
      thrombosis for a gene carrier is difficult to assess, since only some of the
      factors which may finally lead to thrombosis are presently recognized as such.
      The functional tests which are in common use today have a number of drawbacks and
      will soon be replaced by improved methods.

PMID- 9012146
TI  - [Pregnancy and drug dependence].
AB  - A major problem in the treatment of opiate-dependent patients arises due to
      illicit drug abuse capted with drug dependence and pregnancy. Drug abuse during
      pregnancy involves a high risk for the mother as well as for the unborn child.
      Twenty-three pregnant, opiate-dependent women, were enrolled in a 19-month study
      of the outpatient clinic for drug addiction. The mean age of the subjects was
      26.7 years (SD +/- 4.8; range: 20-37 years), the mean duration of opiate
      dependence was 61.8 months (SD +/- 47.5; range: 12-204 months). Seventeen women
      were enrolled in a methadone maintenance program and six women were treated with
      morphine. The babies mean weight at birth was 2746 g (SD +/- 830.1; range: 940
      4370), they had no congenital anomalies and all the maintained babies showed an
      opiate withdrawal syndrome. The treatment yielded in five subjects to a drug-free
      condition at delivery. The application of morphine might be an alternative in
      opiate dependent pregnant women and might reduce the additional consumption of
      illicit drugs during pregnancy.

PMID- 9012147
TI  - [Side effects of travel vaccinations. Data collection via telephone survey in
      Berlin].
AB  - The local and systemic side effects of some frequently administered travel
      vaccines were analysed in a prospective study on 3488 travelers using a
      standardised telephone interview procedure. The vaccines studied were yellow
      fever, diphtheria toxoid (d), tetanus diphtheria toxoid (Td), oral polio (OPV)
      and oral typhoid. Combined vaccinations studied were Td + OPV. Td + yellow fever.
      d + OPV and d + yellow fever. After single vaccination 30% of those inoculated
      reported slight local reactions. 3% had moderate local reactions and 18%
      complained about systemic side effects. After combined vaccinations 47% suffered
      from slight local reactions, 7% had moderate local reactions and 22% developed
      systemic side effects. Of all vaccines studied Td produced the highest frequency
      of local reactions. The combined vaccinations containing yellow fever vaccine
      were less well tolerated than the corresponding single vaccines. Systemic and
      local side effects were experienced more frequently by women, except in the case
      of diphtheria toxoid. Young travelers had more frequent and more severe side
      effects than older travelers after yellow fever vaccination, and after the
      combinations of Td + yellow fever. Td + OPV and d + yellow fever vaccinations.
      The side effects observed were mostly mild and none of the vaccinated travelers
      consulted a doctor for side effects. After travel vaccinations there are
      frequent, but well tolerated local and systemic side effects. Combined
      vaccinations are also well tolerated; their components determine the incidence of
      side effects.

PMID- 9012148
TI  - [Medical performance: ethical and conceptual issues].
AB  - Following an introductory criticism of the Hippocratic Oath and a health
      maximizing principle as ethical basis for health care, an evaluation of medical
      performance is presented according to 3 underlying concepts, namely 1) the act of
      performing medical procedures itself, 2) effectiveness and 3) efficiency. A
      discussion of these issues shows that statements on increasing effectiveness and
      efficiency only make sense if a prior clear definition of the aims of medicine
      can be presumed. Moreover, the achievement of an increase in medical efficiency
      requires quantification of the aims of medicine, whereby it is not self evident
      that these are quantifiable. Certain ethically relevant principles, such as
      justice and self determination, may remain unaffected by such considerations,
      however. Consequently, none of the 3 discussed concepts to measure medical
      performance can be regarded as a sufficient basis for a comprehensive ethical
      evaluation of a health care system.

PMID- 9012149
TI  - [Proceedings of the 3rd Congress of the German Association for Sleep Research and
      Sleep Medicine. Bochum, 19-21, 1995].

PMID- 9012150
TI  - [Stress and fatigue in long distance 2-man cockpit crew].
AB  - Common rules on flight-duty times and rest requirements within the European Union
      are under intense discussion. In the deliberations, results from scientific
      investigations should be considered. As part of a research programme concerning
      legal aspects of two-pilot operations on long-haul routes, the purpose of the
      studies was to investigate two-crew extended range operations during
      transmeridian and transequatorial flight schedules. The studies were conducted
      with two German charter airlines on the transmeridian routes Dusseldorf (DUS)
      Atlanta (ATL) and Hamburg (HAM)-Los Angeles (LAX), and on the north-south route
      Frankfurt (FRA)-Mahe (SEZ) including two consecutive night flights with a short
      layover. In total, 25 rotations (50 flights) have been investigated by pre-, in-,
      and post-flight data collection from the two pilots being the minimum required
      crew. Recordings included sleep, taskload, fatigue and stress by measurements of
      EEG, ECG, motor activity and subjective ratings. During the transmeridian
      schedules, pilots lost one night of sleep because of the return flights which
      were conducted at night. The resulting sleep deficit was 8.2 h. During the
      layover of the SEZ-rotation with a duration of 14 h on average, sleep was
      shortened by 2 h compared with baseline sleep. The two consecutive night flights
      resulted in a sleep loss of 9.3 h upon return to home base. Inflight ratings of
      taskload showed low levels during the atlantic flights, and moderate grades
      during the north-south transitions. Fatigue ratings exhibited an increasing level
      with progressing flight duration. Towards the end of long US-westcoast flights
      performed at day-time, and in all night flights, fatigue was enhanced compared to
      the "baseline" ratings collected during the DUS-ATL flights. Fatigue was scored
      at a critical level by several pilots, particularly during the return flight SEZ
      FRA when fatigue was severely pronounced. The subjective fatigue ratings were
      confirmed by the objective measurements of motor activity, brain-wave activity
      (occurrences of micro-sleep) and heart rate which indicated drowsiness and a low
      state of vigilance and alertness during all night flights under study. From the
      findings it is concluded that duty schedules, as conducted on the route HAM-LAX
      (because of long duty hours), and particularly on the route FRA-SEZ, (because of
      consecutive night duties) are coming close to the limits of mental and
      physiological capacity. With respect to legal aspects, the results have
      significance and should promote further deliberations for advanced schemes of
      flight duty time limitations and rest requirements.

PMID- 9012152
TI  - [Physical performance and sleep in athletes].
AB  - To estimate the activity of the sympathetic nervous system excretion of
      noradrenaline (NA) and adrenaline (A) of members of national teams (8 different
      olympic disciplines) has been looked at. Measured by GC/MS the catecholamines
      showed some characteristics that can be expressed by the NA/A-ratio which is
      independent of sports-discipline, gender and age (17 to 35 years): morning-urine,
      representing sleeping-time, expressed good recreation with NA/A > 10 and
      nervousness followed by low performance with NA/A < 8. Athletes longing for good
      performance may be stressed by time-shift, high-altitude training or by sharing
      their sleeping-room with another person-but nevertheless there are most important
      parallels in the reaction we can see for students during examination-time, shift
      workers and patients. The experience made by measuring NA/A during sleeping time
      of athletes allows to give some physiologically based explanation about effects
      of the sympathetic nervous system. So NA/A-ratio can become an easy to handle
      tool in the field of diagnostic and therapeutic work.

PMID- 9012151
TI  - [Restitutive effect of sleep on chronic performance stress].
AB  - During a polysomnographic (2 nights) sleep registration of 5 chronically stressed
      compared to 5 control persons 24 h blood cortisol values and salivary cortisol at
      daytime were measured and compared with measured stress vulnerability. While
      daytime cortisol levels were reduced under stress conditions, during night sleep
      combined with a significant change in sleep architecture cortisol excretion
      raised markedly compared to controls, and the cortisol response to CRF
      provocation is no more blunted but activated beyond controls, demonstrating the
      restitutive and protective effect of sleep.

PMID- 9012153
TI  - [Sequential analysis of transmission properties of the CNS during consecutive REM
      periods].
AB  - Auditory and visual evoked potentials during sleep were recorded in healthy
      subjects. After averaging of the evoked potentials separately for the different
      REM episodes, the corresponding so-called amplitude-frequency-characteristic was
      calculated. This function describes the transfer properties of the system in the
      frequency domain. Regarding the visual evoked potentials, no difference between
      consecutive REM episodes could be proven. Under auditory stimulation, a
      significant difference between the first and the following REM episodes was found
      in the beta frequency range (12.5 to 20 Hz). This indicates different mechanisms
      of information processing during consecutive REM episodes.

PMID- 9012154
TI  - [REM suppression induced by digital mobile radio telephones].
AB  - In the present study we investigated the effects of pulsed high-frequency
      electromagnetic fields irradiated by digital mobile radio telephones on sleep in
      healthy humans. Besides a hypnotic effect with shortening of sleep onset latency,
      a REM suppressive effect with reduction of duration and percentage of REM sleep
      was found under exposure to the field. Moreover, spectral analysis revealed an
      increased spectral power density of the EEG signal during REM sleep, especially
      in the alpha frequency band. These results emphasise the necessity to carry out
      further investigations on the interaction of this type of electromagnetic fields
      and the human organism.

PMID- 9012155
TI  - [Psychological results of mental performance in sleep deprivation].
AB  - To quantify the effects of sleep periods that have different lengths of time
      during continuous operations (CONOPS) 2 independent groups of subjects performed
      several cognitive tasks for 3 days. The 72 h trial period contained three 60-min
      sleep periods for the 10 subjects of the experimental group and three sleep
      periods of 4 h each for the 14 subjects of the control group. With the exception
      of only one subtest the statistical analyses of the test results of the 2 groups
      show no significant differences in cognitive performance. It is suggested that
      high motivation is responsible for comparable performance of the subjects, which
      was essentially obtained by a monetary pay system for successful test
      performance.

PMID- 9012156
TI  - [Effect of vitamin B12 on sleep quality and performance of shift workers].
AB  - In modern industry shift systems are important for optimal economic utilization
      of high-grade working plants. The implementation of shift systems, however, goes
      along with far-reaching social and health responsibilities of these
      organizations. This study plores, to what extent the intake of vitamin B12 before
      the beginning of a day shift has a stabilizing influence on the quality of sleep
      and the subjective estimate of the performance of the volunteers. The study was
      performed on 10 healthy, male staff members of a Tyrolean industrial plant with a
      mean age of 35 years, who work in a 12/12-h shift system as doormen. In a single
      blind placebo-verum-order all volunteers received first of all placebo for 2
      weeks, then vitamin B12 (Methylcobal, 3 mg) for 3 weeks, at the morning before
      the day shift. By means of modified sleep-onset- and wake-up- records we studied
      the morning and evening state, the estimates of sleep time / -quality as well as
      the subjective judgement of the performance. The statements about periods of rest
      and activity were compared with the objective data of the wrist actimetry.
      Vitamin B12--concentrations in the serum were prepared for baseline and verum
      trials for each individual. In the whole group there were no significant
      differences in sleep-onset and wake-up ratings, nor in the subjective judgement
      of performance between placebo and verum. There were no significant
      particularities with respect to the weekdays or the time of day of activity.
      There was a tendency for the total sleep time in the verum trial to be shorter.
      The mean estimate of sleep quality under verum in significantly higher than under
      placebo in all volunteers.

PMID- 9012157
TI  - [The role of neuropeptides in normal and disordered sleep regulation].
AB  - The neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin
      releasing hormone (CRH) play a key role in sleep endocrine regulation. After
      pulsatile application of GHRH during the first few hours of the night in young
      normal controls SWS and GH increase, whereas cortisol is blunted. CRH however
      prompts inverse effects. The balance between these peptides is changed in favour
      of CRH physiologically during the second time of the night, during the acute
      episode of depression (due to overactivity of GRH) and in the elderly (due to
      reduced activity of CHRH). These changes explain the aberrances of sleep
      endocrine activity in these states, as shallow sleep, low GH and enhanced
      cortisol.

PMID- 9012158
TI  - [Memory performance of Parkinson patients with and without sleep apnea syndrome].
AB  - We investigated the effect of SAS on the long term memory in PD patients and
      compared them with patients with brain infarction or cataract (control group),
      respectively. PD patients develop SAS and cognitive impairments more often then
      healthy people. Since SAS leads to a fragmentation of the sleep structure it
      interferes with memory. Therefore SAS may be a pathogenic factor of cognitive
      impairment in PD. We studied 14 patients (7 with and 7 without SAS) with PD,
      brain infarction or cataract using the LGT-3, which measures the verbal, numeric
      and figural long term memory. All patients answered subtest 7 of the Wechsler
      Memory-Scale at night and in the morning. The saving between the evening and
      morning measure was calculated. An analysis of variance was performed using the
      SAS-condition and the different groups as independent variable. A significant
      difference (p < or = 0.005) of all memory measurements between patients with and
      without SAS but not between the different groups has been proved with a
      superiority of the patients without SAS. A significant difference of the
      influence of the SAS for verbal memory score on patients with PD (pp < or = 0.05)
      and brain infarction (pp < or = 0.005) respectively and the control group could
      be demonstrated. Therefore we found a quantitative difference of memory
      consolidation in PD patients with SAS. The influence of SAS on memory in patients
      with neurological disease is more pronounced compared to the control group.

PMID- 9012159
TI  - [Sleep and breathing disorders in patients with brain stem lesions].
AB  - Most information about the structures within the brain stem that modulate
      respiration and sleep are gathered from animal experiments. Therefore we examined
      10 patients several weeks after an infarction of the brain stem by means of
      polysomnography and tested the chemosensitive drives of respiration. None of
      these patients complained about symptoms of sleep disordered breathing. In each
      case polysomnographic measurements and ventilatory response curves revealed
      pathologic findings. The respiratory response to CO2 was diminished or completely
      abolished in each patient. In some cases hypoventilation or disturbances of the
      respiratory rhythmicity could be seen. In several cases missing REM sleep, sleep
      fragmentation or the reduction of slow wave sleep were observed. The study
      indicates that on the base of results from animal research the comparison of
      morphological and pathophysiological data is helpful to gain a better
      understanding on the coupling of the respiratory system with sleep at the brain
      stem level as well as on the pathomechanism of sleep related breathing disorder.

PMID- 9012160
TI  - [Performance and personality of patients with hypersomnia].
AB  - 5 groups of patients with hypersomnia (narcolepsy, posttraumatic,
      psychophysiologic, idiopathic hypersomnia and circadian sleep-wake disorders)
      were tested with a battery of psychometric tests (FPI, MMPI, BVND, BIV, Benton,
      d2, WIP), visual vigilance test, polysomnography and MSLT in order to investigate
      the context between personality and performance. MSLT showed a range from clear
      pathologic to borderline sleep latencies among all groups, only patients with
      posttraumatic hypersomnia and narcolepsy displayed sleep onset REM. Correct
      results of vigilance tests correlated negatively with performance-motivation and
      orientation in patients with narcolepsy and posttraumatic hypersomnia, whereas
      there was positive correlation for patients with idiopathic hypersomnia. In
      patients with psychophysiologic hypersomnia performance orientation and false
      reactions correlate negatively. Patients with posttraumatic hypersomnia have
      better results on d2. Benton and vigilance tests than all other groups. Results
      of personality diagnosis are similar to those of healthy subjects, while patients
      with psychophysiologic hypersomnia are more sensible than all other groups with
      high social fears and the highest disposition among all groups toward somatic
      complaints. Patients with idiopathic hypersomnia show strong introversion and
      inhibition. Patients with circadian sleep-wake disorders display the most
      striking personality disorders, which are most probably sequelae of their strong
      disease-dependent impairment. The degree of personality disorder seems to be
      strongly dependent on the duration of the hypersomnias. The assessment of the
      whole set of tests can only be recommended for patients with psychophysiologic
      hypersomnia and circadian sleep-wake disorders, a few tests suffice to describe
      the other groups.

PMID- 9012161
TI  - [Interpersonal psychotherapy in treatment of patients with primary insomnia-
      preliminary data of polysomnographic macro-analysis].
AB  - There has not been done much research on psychotherapeutic treatment of patients
      with primary insomnia. Interpersonal psychotherapy for insomnia (IPT-I)
      represents a new causal strategy in the treatment of insomnia, which has been
      evaluated in this study. 25 patients were treated in 12 single sessions either
      with IPT-I or with progressive relaxation training. Preliminary polysomnographic
      data show significant improvement of total sleep time, sleep efficiency and wake
      after sleep onset of the IPT-I-patients, while the PR-patients only improved
      slightly. IPT-I therefore was shown to be a promising strategy in the treatment
      of patients with primary insomnia.

PMID- 9012162
TI  - [Sleep complaints and hypnotic use by the elderly--results of a representative
      survey in West Germany].
AB  - For the first time, a country-wide group of West-Germans were interviewed
      regarding their sleep complaints and hypnotic intake. Therefore 344 persons who
      were older than 65 years and 1653 subjects between the age of 14 and 65 years
      were representatively selected by a random route system. Around the age of 45 the
      prevalence of sleep-disturbances starts rising continuously and dramatically.
      Over the age of 65 nearly half of the West-Germans (43%) suffer from difficulties
      in initiating and/or maintaining sleep (DIMS) at least sometimes, 15% suffer
      frequently or always from these complaints. 79% of the sleep disturbed elderly
      (over the age of 65) are chronically ill, having sleep-complaints for more than 2
      years or since childhood. The hypnotika intake increases with age as well. Around
      45 years of age the irregular hypnotika intake (several times the year or month),
      and after 55 years of age, regular hypnotic intake (daily or several times the
      week) rapidly rises. After 65 years of age hypnotic intake increases much more
      than the sleep complaints do. So, every third elderly person (34%) takes
      hypnotics at least irregularly. The results of this study indicate that sleep
      complaints in the elderly are three times more common and more severe than in
      younger persons, and that they tend to chronify while treated with hypnotics.

PMID- 9012163
TI  - [Subjective diurnal fatigue and sleep deprivation response].
AB  - 29 major depressive patients, the majority suffering from a melancholic subtype
      and typical diurnal variation of mood, rated subjective tiredness on a 100 mm
      analogous scale before and after total sleep deprivation (TSD). In study A every
      four hours during the day before and after TSD and every 2 hours during the TSD
      night ratings were performed, in study B at 8.00 a.m. before and after TSD. The
      mean response rate was 55.2% in the 2 studies. In study A subsequent responders
      were less tired during the afternoon before TSD. Responding patients were more
      alert the morning after sleep deprivation than non-responders. A higher inter
      individually variability of tiredness ratings in responders before and after
      sleep deprivation was found in study B, assuming an arousing property and a
      greater variability in subjective arousal at least during the morning hours. In
      summary the determination of the subjective arousal level may help to predict
      response.

PMID- 9012164
TI  - [Clozapine, cytokines, fever and sleep].
AB  - In 27 schizophrenic patients we investigated plasma levels of cytokines before
      the initiation of treatment and after the first, second and sixth week of
      treatment with the atypical antipsychotic agent clozapine. In addition, we did
      polysomnographic recordings in one schizophrenic patient prior to, during and
      following clozapine-induced fever. We found that independently of fever clozapine
      significantly increased the plasma levels of tumor-necrosis-factor a (TNFa) and
      soluble interleukin-2-receptor (sIL-2r) which were further increased by fever.
      Interleukin-6 (IL-6) was increased only together with fever and showed a
      significant positive correlation with clozapine-induced fever. The sleep
      recording of the fever night revealed severely disturbed sleep. Possible links
      between the clozapine-induced release of cytokines and clozapine's effect on
      night sleep are discussed.

PMID- 9012165
TI  - [Nonlinear dynamics in regulation of heart rate in healthy infants].
AB  - The aim of this study was to investigate qualitatively and quantitatively non
      linear and linear characteristics of heart rate identifying their connection to
      sleep states during the first 6 months of life. 16 newborns were examined
      polygraphically in a longitudinal study (first day, first and sixth month). After
      R-peak detection of a limb lead ECG and R-R interval calculation, time series of
      the instantaneous heart rate (IHR) were constructed. They were analyzed
      qualitatively with regard to the structure of the Poincare maps and the
      occurrence of bifurcations as well as quantitatively by calculating the
      correlation dimension (D2) and the Lyapunov exponent (LLE). In some cases,
      bifurcations in the IHR time series occurred. The Poincare maps showed mainly
      clear structures in the shape of limited point clusters. D2 was in the range of
      1.5 to 2.5 and was larger in quiet than in active sleep. LLE was always positive,
      although higher values in active sleep than in quiet sleep were exhibited in the
      first month of life only. D2 and LLE values during active sleep were age
      dependent. The results of the study indicate a non-linear component in the heart
      rate control of healthy newborns. The change in D2 and LLE in connection with
      postnatal age and sleep states expresses a modulation of these system components
      during the postnatal maturation and during vegetative sleep organisation.

PMID- 9012166
TI  - [Periodic breathing with periodic oxygen variation in infancy].
AB  - Oxycardiorespirographies, recording arterial oxygen saturation (SaO2), breathing
      movements, heart rate and ECG with a mean recording time of 22.3 hours, were
      performed on 85 preterm (mean postconceptional age: 38 weeks) and 81 term infants
      (mean postconceptional age 42.4 weeks). 83% of the preterm infants showed
      periodic breathing (PB), in 97% of them this was accompanied by periodic
      variations of arterial oxygen saturation (PVO). Periodic breathing occurred in
      61% of the term infants, 84% of them showed PVO during periodic breathing. The
      mean variation of oxygen saturation was between 92.8 and 96.8% (+/- 1.7) for
      preterm and between 92.9 and 96.0% (+/- 2.2) for term infants. In some infants
      the peak to peak amplitude of the SaO2 cycles was up to 22%, sometimes a further
      fall of SaO2 occurred. There was a strong correlation of the PVO both at the
      beginning and end of the episode as well as with the PB-cycle periodicity itself.
      The fall of the oxygen saturation occurred 3.1 to 7.8 s after the beginning of
      the first apnea of an episode of periodic breathing, the minimum SaO2 was reached
      approximately 4.2 to 8.6 s later. This periodic rapid fall of SaO2 from a high
      oxygenation level cannot be explained by the apneas of a rather short duration
      during periodic breathing. It is discussed that PVO during periodic breathing may
      be caused by an ideopathic right to left shunting across fetal circulation
      pathways which occurs intermittently and periodically. This mechanism could-via
      patterns of reaction exhibited during the fetal and neonatal time period-lead to
      acute hypoxemia, as found in apparently life threatening events (ALTE) and as
      postulated in sudden infant death (SID).

PMID- 9012167
TI  - [Methodology and problems in home monitoring of children with sleep-related
      respiratory disorders--perspectives].
AB  - In a pilot study we interviewed parents of 100 formerly home monitored infants
      about problems during the monitoring period. The duration of home monitoring was
      between 1 and 48 months (median 15 months). 95% of the parents reported false
      alarms. 66% of the infants had real alarms, in 50% of the infants interventions
      were necessary. 3% of the infants had to be resuscitated. Only 47% of the parents
      felt safe in the practice of resuscitation even though all parents had been
      trained before. Perspectives of improvement of home monitoring are discussed.

PMID- 9012168
TI  - [Apnea characteristics of children who later died: comparison of sudden infant
      death with other causes of death].
AB  - Apnea characteristics of infants, who were destined to die, were compared with
      control infants, matched for gestational age, sex, birth weight and age at sleep
      study. From 1989 to 1994 polygraphic recordings were performed in 4268 infants.
      In this population 7 cases of sudden infant death (SID) and 13 deaths from other
      causes (non-SID) occurred. Concerning all forms of apneas a higher frequency and
      maximal duration was found in the SID group. The number of infants with
      obstructive apneas and the number of obstructive apneas per infant were higher in
      future SID victims, as was the frequency, mean and maximal duration of central
      apneas of 3 to 10 s. The recordings of non-SID-infants were not different from
      their controls. As a group, future SID victims showed apnea characteristics
      different from control infants. Together with epidemiologic risk factors these
      polygraphic factors contribute to an identification of infants at risk for SID.

PMID- 9012169
TI  - [Continuous ambulatory monitoring in quality control of home therapy of
      congenital central hypoventilation syndrome (CCHS)].
AB  - 4 children with congenital central hypoventilation syndrome (CCHS) now aged 6 to
      9 years were studied for 1 to 8 years. In all patients CO2-response is missing,
      hypoxic drive is maintained. All patients required mechanical ventilation after
      birth. 1 patient is supported by controlled oxygen therapy during sleep since 9
      months of age. 2 patients are IPPV-ventilated during sleep. 1 patient is pressure
      control ventilated with an oro-nasal mask since 6 years of age. All children
      showed phases of hypo- and hyperventilation (max. pCO2 107 mm Hg) depending on
      vigilance with respiratory acidosis in awake state and during sleep. These
      findings required ambulatory monitoring of home-therapy by a professional guard
      and continuous recording of pCO2 and pulseoximetry. These longtime data (max.
      pCO2 72 mm Hg) show that ambulatory monitoring and control of therapy is able to
      avoid extreme variation of blood gases and to stabilize acid-base regulation
      during sleeptime in patients with CCHS.

PMID- 9012170
TI  - [nCPAP/nBIPAP therapy in sleep-related obstructive respiratory disorders in
      childhood].
AB  - nCPAP/nBIPAP-therapy is a possibility of treatment of sleep related disturbances
      also in childhood. We will demonstrate the therapeutic effect of therapy in 13
      patients in the age range 3 to 14 years on behaviour, school performance, number
      of infections in the upper airways as well as on polygraphic parameters, i.e.,
      sleep structure, number of apneas, oxygen saturation and mean heart rate.

PMID- 9012171
TI  - [Effect of adenotomy on mental performance of children with adenoid vegetations].
AB  - Mental capacity, assessed by several anamnestic questions, was improved by
      adenoidectomy in 46 children with adenoid vegetations and was influenced by
      hypoxic episodes during sleep. Hypoxic desaturations during sleep can be
      predicted by 5 anamnestic and clinical parameters (specificity 70%, sensitivity
      85%).

PMID- 9012174
TI  - [Driving performance and auto accidents in patients with sleep apnea].
AB  - Obstructive sleep apnea is a common disorder in which the airway repetitively
      collapses during sleep; patients with sleep apnea are often inattentive and
      sleepy. This review discusses driving performance and automobile accidents in
      patients with sleep apnea. Finally, we discuss the effect of therapy upon driving
      performance and reported accidents in these subjects.

PMID- 9012172
TI  - [Sleep structure in relation to respiration and heart rate in children in
      puberty].
AB  - The different expression of respiratory sinus arrhythmia in REM- versus nonREM
      sleep indicates a dependence of cardiorespiratory interaction on patterns of
      sleep. Investigations of the intensity of respiratory entrainment on heart
      rhythmicity during various stages of sleep will provide an insight into the
      coupling of cardiorespiratory interaction and sleep patterns. 42 healthy children
      (12 to 15 years old) were polygraphically investigated over 24 h. An ECG, EOG,
      and actogram were performed, respiratory movements were observed, and the skin
      temperature was taken. The power spectra of the instantaneous heart rate and the
      respirograms were calculated. The analysis of coherence was carried out to
      determine how pronounced the cardiorespiratory interaction is. REM-sleep, nonREM
      phases, and wakefulness were compared. The spectral parameters of instantaneous
      heart rate show differences between both stages of sleep and the waking state.
      Due to a dependence of spectral power on breathing patterns, drawing quantitative
      conclusions is not possible. The analysis of coherence provides more information
      about sleep patterns within the cardiorespiratory interaction. It is very
      pronounced during non-REM-sleep (0.80 +/- 0.07; mean +/- standard deviation).
      Heart rhythmicity proceeds independent of breathing during REM-sleep (0.52 +/-
      0.11). The coupling is weaker than during wakefulness (0.64 +/- 0.09).

PMID- 9012175
TI  - [Risk of accident due to hypersomnia: relevance for sleep medicine].
AB  - Hypersomnia is increasingly recognized as a potential causal factor for
      accidents. Information of the general public about scientific knowledge on the
      area of fatigue and sleepiness is, as well as the recognition and treatment of
      disorders impairing vigilance, an important task for sleep medicine. Fulfilling
      this task will warrant an important contribution to increase road safety. Sleep
      related disordered breathing is an example that shows the sense and the need for
      a qualitatively good medical care of patients with sleep related disorders.

PMID- 9012173
TI  - [Sleep fragmentation as the cause of daytime sleepiness and reduced performance].
AB  - Studies in healthy young adults revealed that periodic arousals during the night
      result in increasing sleepiness as a function of the interval of time between
      arousals. When arousals are frequent, deficits similar to those seen after total
      sleep deprivation have been found. Observed decrements appear to be specifically
      related to EEG arousals and do not require complete awakening. In patients with
      fragmenting sleep disorders such as periodic leg movements and central sleep
      apnea, improved nocturnal sleep is related to increased alertness and daytime
      performance.

PMID- 9012176
TI  - [Modification of cardiopulmonary performance parameters in patients with
      obstructive sleep apnea treated with nCPAP therapy].
AB  - nCPAP influences cardiopulmonary hemodynamic function in patients with
      obstructive sleep apnea (OSA). It is known that systolic function of the right
      and left ventricle, systemic and pulmonary hypertension, arterial blood gases and
      lung function during the day may improve under this treatment. We prospectively
      followed 30 patients with severe OSA and determined diastolic left ventricular
      function (Doppler echocardiography), cardiovascular efficiency (steady state
      exercise stress testing); and individual assessment of performance (standardized
      psychometric questionnaire) before, and 2 weeks and 6 months after initiation of
      nCPAP treatment. The following results could be obtained (first value after 2
      weeks, second value after 6 months): Doppler echocardiography: E/A rose by 9.3%
      (p < 0.05) and another 0.5% (n.s.). E/A integral increased by 13.8% (p < 0.01)
      and another 3.5% (n.s.). Deceleration period decreased by 22.7% (p < 0.01) and
      another 3.1% (n.s.). Steady state exercise stress testing: Maximum performance
      rose by 10% (p < 0.05) and another 17.5% (p < 0.01). Heart rate ratio 100 W/rest
      dropped by 13.5% (p < 0.001) and another 6.5% (p < 0.01), systolic blood pressure
      ratio 100 W/rest by 0.8% (n.s.) and another 14.9% (p < 0.001). Diastolic blood
      pressure ratio 100 W/rest did not change significantly. Questionnaire: Assessment
      of well-being increased by 44.5% (p < 0.05) and another 16.9% (n.s.). After an
      initial drop of 0.8% (n.s.), quality of life increased by 14.9% (p < 0.05).
      Assessment of performance rose by 21.7% (p < 0.05) and another 4.1% (n.s.). nCPAP
      therapy in patients with OSA improves diastolic function of the left ventricle,
      cardiovascular performance and individual assessment of performance.

PMID- 9012177
TI  - [Assessment of attention parameters in sleep apnea patients].
AB  - In the current study the modality-shift paradigm was applied to examine attention
      deficits in sleep-apnea patients. The reaction times of ipsi- and crossmodal
      light and sound stimuli were measured on 34 patients presenting symptoms of sleep
      apnea. Some of the simple reaction times of ipsimodal (light-light; sound-sound)
      and crossmodal (light-sound; sound-light) stimuli correlated with mean or with
      minimal oxygen saturation, but did not correlate with the frequency or duration
      of obstructive apneas and hypopneas. However, results are different if the amount
      of modality-shift effect is taken into consideration. Significant correlations
      were found for the maximal duration of obstructive apneas and hypopneas as well
      as for mean oxygen saturation.

PMID- 9012178
TI  - [Obstructive sleep apnea in patients with coronary heart disease].
AB  - Patients with obstructive sleep apnea have an increased cardiovascular morbidity
      and mortality, those with co-existent coronary artery disease being particularly
      at risk. The object of our study was to evaluate the prevalence of obstructive
      sleep apnea in patients with coronary artery disease. 153 patients (117 men, 36
      women) with verified coronary artery disease were given a highly sensitive
      standardized questionnaire. The 59 patients with pathological results were then
      checked with a 6-channel non-laboratory monitoring system. 22.2% of all patients
      had a respiratory disturbance index (RDI) above 5/h. and 14.4% above 10/h. 13.3%
      had a pathological RDI and additionally suffered from excessive daytime
      sleepiness. Patients with coronary artery disease have a high prevalence of
      obstructive sleep apnea and should consequently be screened for this sleep
      related breathing disorder.

PMID- 9012179
TI  - [Anamnestic and polygraphic parameters in obstructive sleep apnea syndrome
      patients with reduced nasal respiration during the day in comparison with
      obstructive sleep apnea patients with normal nasal respiration].
AB  - Nasal obstruction is a predictive factor for snoring and may contribute to the
      development of an obstructive sleep apnea syndrome (OSAS). The aim of this study
      was to further evaluate the impact of nasal obstruction in OSAS. Therefore, we
      investigated 2 groups of OSAS-patients, matched pairs concerning gender, age, and
      BMI: OSAS-patients with nasal obstruction (N, n = 28), total nasal airflow < 500
      ccm/s (referred to 150 pa pressure of difference or unilateral nasal resistance >
      1 pa/ccm/s), and 28 OSAS-patients without nasal obstruction (control-group K,
      total nasal airflow > 700 ccm/s [referred to 150 pa pressure of difference or
      unilateral nasal resistance > 1 pa/ccm/s]). We performed anterior rhinomanometry,
      lung-function testing, cardio-respiratory polygraphy, and patients answered a
      standardized questionnaire. We found the following significant differences: 1) N
      complained more often (n = 17) about dyspnea at night than K (n = 7, p < 0.05,
      Chi2-test). 2) N had a higher apnea index (20.4 +/- 19.0/h) than K (9.6 +/-
      10.0/h, p < 0.05, Student's t-test). There were, however, no significant
      differences concerning lung function, number of nocturnal hypopneas, nocturnal
      SaO2 and heart rate. Our results underline the importance of nasal ventilation in
      the pathogenesis of OSAS. At least in moderate cases of OSAS a therapy of nasal
      obstruction might be of success in order to abolish nCPAP-therapy or might reduce
      nasal problems during nCPAP-therapy and thus ameliorate patient's therapy
      compliance.

PMID- 9012180
TI  - [Signs of right heart stress in diurnal normoxemic patients with chronic
      obstructive lung disease and nocturnal hypoxemia].
AB  - Nocturnal hypoxemia in daytime normoxemic patients with COPD may lead to an
      increased right ventricular afterload due to pulmonary hypertension. We
      investigated the frequency of clinical, electrocardiographical, and radiological
      signs of right cardiac insufficiency (SRCI) in 178 consecutive COPD-patients [71
      bronchitis, 25 emphysema, 82 bronchitis plus emphysema; PaO2 = 60 mm Hg].
      Patients with asthma, left ventricular impairment, obstructive sleep apnea
      syndrome, primary pulmonary hypertension, and neuromuscular diseases were
      excluded. Polysomnography was performed in all patients. They were divided into 3
      groups concerning SRCI: missing, doubtful, and secure SRCI. Parameters of
      nocturnal pulse oximetry were analyzed within the three groups (Student's t-Test.
      Chi2-Test. p < 0.05). 25.8% of the patients had secure SRCI without a significant
      frequency difference between patients with bronchitis and/or emphysema. Patients
      with secure SRCI had a significant lower mean nocturnal SaO2 than those with
      missing SRCI (92.7 +/- 2.5 vs. 90.3 +/- 3.5%). With regard to the high prevalence
      of SRCI in association with nocturnal hypoxemia routine control of nocturnal
      oxygenation is recommended in daytime normoxemic COPD-patients for the early
      decision for nocturnal oxygen therapy.

PMID- 9012181
TI  - [Difficult patients in the sleep laboratory--nCPAP therapy in psychiatric
      patients with sleep apnea disorders].
AB  - 160 unselected patients under suspicion of sleep apnea were examined
      polysomnographically, 26 patients (16%) had relevant psychic disorders, which
      were classified according to ICD-10 by the psychiatric consultant. Affective
      depressive disorders (n = 12) and neurotic disorders (n = 11) were diagnosed.
      Depression in 3 patients was primarily diagnosed in the sleep laboratory. A
      proper anamnesis can supply the doctor with helpful hints for psychic disorders.
      These disorders can complicate or prevent the diagnosis and therapy in the sleep
      laboratory.

PMID- 9012182
TI  - [Microbiological studies of a nasal positive pressure respirator with and without
      a humidifier system].
AB  - 13 patients with obstructive sleep apnea syndrome treated with CPAP-therapy and
      complicating affections of the nasal and pharyngeal mucosa were enrolled in a
      randomized cross-over study comparing therapy with a heated humidifier (HC 100,
      company Fisher & Paykel) and treatment with a heat and moisture exchanger (Typ I,
      company Dahlhausen). We assessed the bacterial and fungal colonisation of the
      nasal masks of all patients. Samples of mask rinses were taken after the two
      treatment periods (2 weeks each) and the period without humidification in
      between. All microbes were found to have pathological potency. There was no
      significant difference in the total concentration of the microbes in the
      different treatment modalities. In a few cases however, gram negative bacteria
      were detected on the masks during humidification with a heated humidifier, but
      not with heat and moisture exchangers. Legionella spec. were not detectable in
      any of the samples. Candida albicans was the only fungus detectable. No patient
      had any infection of the upper or lower respiratory system associated with
      humidification therapy.

PMID- 9012183
TI  - [Sex-specific sleep anamnesis in obstructive sleep apnea syndrome?].
AB  - Although the prevalence of obstructive sleep apnea syndrome (OSAS) is about 4% in
      men and 2% in women, women are underrepresented in clinical routine. The aim of
      this study was to determine whether differences in clinical features of OSAS may
      in part explain the bias observed. 224 men and 24 women with polysomnographically
      confirmed OSAS filled in a symptom-focussed multiple-choice questionnaire.
      Polysomnographical results were comparable in both groups. With regard to
      snoring, daytime sleepiness and tendency of falling asleep there were no
      differences between both groups. Women more frequently complained about
      difficulties of initiating and maintaining sleep and about apneas. Further
      investigations have to concentrate on the pathomechanisms of OSAS in women which
      may in part explain the gender differences in sleep apnea associated symptoms.

PMID- 9012184
TI  - [Spectral analysis of blood pressure in patients with sleep related respiratory
      disorders].
AB  - Spectral analysis is a helpful tool to investigate the interaction of blood
      pressure, respiration and sleep (6). The analysis of systolic pressure is most
      suitable for the documentation of compressed spectral arrays, since there are
      less disturbances than from the heart rate. The method used in this study allows
      the discrimination and quantitative evaluation of periodic blood pressure
      oscillations associated with apneic and breathing phases. It could be shown that
      the amplitude of the pulsus paradoxus increases during episodes of obstructive
      snoring. Heavy snore showed rather stable respiratory frequencies during the
      whole night which was not found that distinctly in patients with obstructive
      sleep apnea. The parallel analysis of blood pressure variations and sleep phases
      revealed different mechanisms in the regulation of REM- and non-REM sleep which
      transfer sleep related breathing disorders from a periodic pattern in a
      nonperiodic one and hereby influence at least the regulation of heart rate and
      blood pressure.

PMID- 9012185
TI  - [Severity of obstructive sleep apnea syndrome--correlation with cephalometric
      parameters].
AB  - In 132 patients with polysomnographic records suffering from OSAS a cephalometric
      analysis according to Hasund supplemented by special OSAS-parameters was
      performed. The statistical analysis showed a correlation between severity of OSAS
      and width of posterior airway space, length of the soft palate, hyoid position
      and posterior growth development of the mandible. A principal component analysis
      showed four groups: 1) prognathic patients, 2) retrognathic patients with narrow
      PAS, 3) patients with long soft palate and low standing hyoid, and 4) orthognatic
      obese subjects. Lateral cephalometry is an important contribution to OSAS
      diagnostics and should be performed on all OSAS patients in the course of
      interdisciplinary cooperation.

PMID- 9012186
TI  - [Functional palatoraphy and modified chin osteotomy in surgical therapy of sleep
      related respiratory disorders with obstruction of the upper airways].
AB  - We have developed a new surgical approach, called functional palatoraphy. This
      procedure preserves the posterior border of the soft palate and allows a
      controlled repair of the soft palate. It is routinely combined with a chin
      osteotomy. In selected cases this procedure is an alternative to other surgical
      methods.

PMID- 9012187
TI  - [Functional palatoraphy and modified genioplasty in obstructive sleep apnea].
AB  - 10 patients with obstructive sleep apnea syndrome (OSAS) have been treated with
      the new surgical procedure functional palatoraphy and modified genioplasty. 5
      months after surgery 7 patients with an apnea hypopnea index under 10 were cured.
      Three therapy refractory patients were all overweight with a body mass index of
      more than 29 kg/m2. Excessively overweight patients should therefore not be
      operated. Following the selection criteria we introduced an effective new
      treatment method for OSAS.

PMID- 9012188
TI  - [Principles of surgical treatment of obstructive sleep apnea by interventions on
      the facial bones].
AB  - The clinical picture of the obstructive sleep apnea syndrome is caused by a
      multifactorial etiology. Therefore a lot of different conservative as well as
      surgical therapeutic approaches are discussed. In approximately 40% of the
      patients an obstruction of the pharyngeal airway is combined with an abnormal
      sagittal morphology of the skull. In these cases a simultaneous maxillomandibular
      advancement by at least 10 mm seems to be a causal therapy, leading to an
      enlargement of the pharyngeal airways. The current therapeutic results are
      roughly stable up to a period of approximately 3 years. Requirement of this
      therapy is the exclusion and/or the prior therapy of an extreme obesity, which
      can favour the manifestation of an obstructive sleep apnea syndrome.

PMID- 9012189
TI  - [nCPAP therapy and maxillary and mandibular osteotomy compared: attention during
      the day in obstructive sleep apnea].
AB  - 11 patients with obstructive sleep apnea (OSA) and maxillary and mandibular
      characteristics participated. All patients received nCPAP therapy for at least 3
      months. The surgical treatment principle consists of 10 mm maxillary and
      mandibulary advancement. Cardiorespiratory polysomnography (cPSG) control was
      assessed 3 months after surgical treatment. The daytime vigilance was
      investigated using a 90-min 4-choice reaction-time test. Patients reports of
      excessive daytime sleepiness (EDS) were confirmed by pre-treatment vigilance
      testing. Accordingly, daytime vigilance, respiratory and polysomnography patterns
      were improved with nCPAP and surgical treatment in a likewise manner. The
      tolerance to monotonous situations increased distinctly with nCPAP as well as
      after osteotomy. Surgical treatment of OSA in carefully selected cases has
      positive effects on sleep and daytime vigilance. There were no significant
      differences in the cPSG nor in vigilance tests with regard to nCPAP therapy.

PMID- 9012190
TI  - [Detection of muscle fatigue with electromyography].
AB  - During fatiguing contractions of muscles typical changes in the surface
      electromyogram (EMG) are found, like an increase in the EMG amplitude and a shift
      of the frequency spectrum towards lower values. Such changes can be used to
      indicate the occurrence of muscular fatigue. It has to be considered that EMG
      changes not only depend on muscular fatigue but also on the contraction force of
      the muscle under test. Suitable methods are shown which can, according to this
      condition, be applied for the determination of muscular fatigue occurring during
      occupational work.

PMID- 9012191
TI  - [Computer-assisted analysis of sleep stages using the laboratory software package
      "Spike 2"].
AB  - We used a laboratory software package for data capture and data analysis (Spike
      2, CED) to develop a computerised sleep staging. The modular software is
      programmed to extract the following data: power spectral density in the alpha and
      delta frequency bands with fast Fourier Transformation, K-complexes using pattern
      recognition on the basis of signal amplitude and zero level crossings, sleep
      spindles using auto-correlation of the EEG signal, rapid eye movements with
      pattern recognition of the bipolar EOG signal using amplitude and time
      differences, and muscle tone from the rectified and integrated submental EMG
      signal. These results are displayed together with the raw signals of EEG, EOG,
      and chin EMG on a user-defined time scale. Thus visual scoring of sleep stages is
      easter. Furthermore a decision table, containing the sequence and weighting
      factors for the extracted parameters, serves to perform an automated sleep
      scoring.

PMID- 9012192
TI  - [Significance of oscillatory impedance in etiological determination of arousal in
      sleep related respiratory disorders].
AB  - Conventional registration of cardiorespiratory data may not explain daytime
      sleepiness in some patients. Polysomnography may detect arousal reactions that
      can only be explained by additional registration of esophageal pressure. We
      developed a device (oscillatory impedance [OI]) which applies an oscillating flow
      via a nasal mask that allows to detect the pathophysiologic findings of upper
      airway resistance syndrome. 25 patients (age 47.3 +/- 5.6 years, body mass index
      26.6 +/- 3.8 kg/m2) underwent conventional polysomnography and additional
      measurement of OI. In 59% arousal reactions could not be explained by respiratory
      data whereas OI demonstrated intermittend obstruction of extrathoracic airways.
      We therefore conclude that patients with daytime sleepiness that cannot be
      explained by conventional polysomnographic registrations should undergo
      measurement of OI.

PMID- 9012193
TI  - [Long-term analysis of respiration in sleep].
AB  - We completed polysomnography and complementary measurement of the oesophageal
      pressure and airflow in 6 subjects (2 volunteers, 4 patients with sleep-related
      breathing disorder). The evaluation of the physiological parameters of the
      breathing over the whole night showed a strong correlation between the pressure
      time product and the work of breathing. Our results revealed distinct differences
      between the parameters of the breathing mechanics in volunteers versus in
      patients. The continuous long-term analysis of respiration during sleep may
      contribute to reveal further pathological mechanisms of the respiratory system.

PMID- 9012194
TI  - [Effect of automatically titrated CPAP systems on sleep and respiration in sleep
      apnea syndrome].
AB  - We compared an automated self setting CPAP-titration with conventional constant
      CPAP. In 12 patients with obstructive sleep apnea syndrome 2 polysomnographies
      were performed after introduction of CPAP-therapy. In a randomized cross-over
      study a constant CPAP during one night and in a second night a computerized
      variation of pressure was applied by a self-setting CPAP-device (Auto AdjustTM
      CPAP). During both methods apneas, hypopneas and snoring were reduced. Apnea
      index was reduced from 32.5 +/- 28.5 at diagnosis to 3.3 +/- 4.7 by Auto Adjust
      CPAP and to 4.0 +/- 5.3 by constant CPAP. The results of the 2 methods were not
      significantly different. Total sleep-time, sleep efficiency and sleep stages did
      not show any significant difference. CONCLUSIONS: In case of pressure-intolerance
      automated self setting CPAP offers an alternative beneath BiPAP. The significance
      of this method with regard to BiPAP therapy must further be evaluated.

PMID- 9012195
TI  - [Pupillography as an objective attention test].
AB  - Infrared video pupillography (IVP) allows continuous recording of spontaneous
      pupillary oscillations in darkness which change characteristically with fatigue.
      Pupil size in darkness is age-related, has its maximum in the second decade and
      subsequently decreases during life time. Normally, the pupil oscillates in
      darkness with a frequency of about 1 Hz and amplitudes of less than 0.3 mm.
      Excessive daytime sleepiness causes instability of this pupillary behaviour which
      is constant in alert normals, and so called fatigue waves appear with an
      amplitude reaching several millimeters. The frequency profile is dominated by
      slow frequencies below 0.5 Hz, while average pupil size decreases continuously
      with time. As IVP is an objective and time-saving method it could become an
      important supplement to test procedures used in sleep medicine and sleep research
      to measure daytime sleepiness.

PMID- 9012196
TI  - [Value of registering nocturnal REM phase related erections in diagnosis of
      erectile impotence].
AB  - A recently published field study from Boston, USA, showed an incidence of
      complete erectile dysfunction of 9.6% in 1290 men between 40 to 70 years. The
      invasive diagnostic schedule based on intracavernous pharmacon injection since
      1982, continues to be dependent on the individual adrenergic tonus of the patient
      influenced by stress and fear. False-positive results are often found and
      consequently lead to strictly somatic therapeutic approaches like microsurgical
      vascular procedures or prosthetic implants. Computerized registration of
      nocturnal REM-phase correlated erections (NPTR-measurements) enables the examiner
      to evaluate the principal erectile capacity of intracavernous erectile tissue
      independently from psychic disturbances, if well standardized evaluation criteria
      are used.

PMID- 9012197
TI  - [Aspects of medical expert assessment of sleep-waking disorders].
AB  - Knowledge gained in sleep medicine over the past 10 years has not yet been
      incorporated into laws for the severely handicapped and pension law. The impact
      of increased accident incidence of patients with hypersomnia has not yet been
      recognized in the guidelines for medical diseases in automobile traffic in
      governmental driving regulations. In preparation for implementation of sleep-wake
      disorders into medico-legal jurisdiction they must be introduced to the
      guidelines as a separate medical entity according to the International
      Classification of Sleep Disorders. Due to different prognoses sleep-wake
      disorders should be separated into reversible and irreversible disorders. To
      decide on driving ability, degree of disablement and permanent and total
      disability therapeutic efficiency should be documented by methods acknowledged in
      sleep medicine. Professional and nonprofessional drivers and personnel in charge
      of responsible monitoring should be submitted to regular therapy controls. Degree
      of disablement or permanent and total disability can only be recommended for
      patients with symptoms partially or completely refractory to therapy.
      Accompanying diseases posing a high health risk or those causing sleepiness
      themselves have to be included in the overall judgement. Sleep specialists have
      to be nominated as expert witnesses and should furthermore contribute to
      multiplication of knowledge on sleep medicine for public health officers.

PMID- 9012198
TI  - [Economic aspects of sleep medicine].
AB  - According to its rules it is the task of the German Sleep Research Society (DGSM)
      to promote scientific research in the area of Sleep Medicine in Germany and to
      transform scientific results into clinical practice for the benefit of patient
      care. The international classification of sleep disorders (ICSD) distinguishes
      more than 80 different disorders which can be treated due to scientific progress
      which has been made over the last 50 years. The conversion of established
      scientific knowledge in the field of sleep medicine into an improved clinical
      management of patients should not be prevented by the lack of sufficiently
      equipped sleep units. The federal government has stated that, due to financial
      constraints, it would not consent to any measures which might lead to a budget
      increase, such as case oriented special payments for certain diseases. Thus, an
      adequate number of sleep units can only be provided by integrating these units
      into the budget of the respective hospitals and departments, paid by the local
      insurance companies, thus providing the necessary financial resources to the
      sleep units. Many services in the area of sleep medicine can be covered by the
      existing reimbursement system. In some cases, however, a definite diagnosis can
      only be made by the use of complete polysomnography (PSG). For a complete PSG the
      additional costs have been calculated by the DGSM to be 1195,-DM per 24 h. Sleep
      units dealing with both diagnostically and therapeutically complex cases such as
      patients requiring complex forms of nasal ventilation, depend on an increase in
      the reimbursement by the insurance companies to cover the expenses involved. For
      each sleep unit, a "case-mix" can be calculated which will include both complex
      and less complex cases. The costs using this case mix will be considerably lower
      than the cost for a complete PSG. Sleep units provide the basis for education and
      quality assessment which are necessary for competent patient management in the
      future. Adequate diagnostic and therapeutic facilities in sleep medicine provide
      the basis for patient care, contribute to improved health standards and, thus,
      reduce social costs of these frequent diseases.

PMID- 9012199
TI  - [Cross-reacting allergens--panallergens].
AB  - In the last few years a dramatic increase of the prevalence of immediate type
      allergies (Type I hypersensitivity according to Coombs and Gell) could be
      observed. In order to study pathomechanisms which are operative in allergic
      disease it is highly important to identify and to characterize substances which
      actually elicit sensitization-the allergens. Allergens are characteristically
      proteins derived from and/or present in plants or animals. Analysis of allergens
      using molecular biology revealed that particular allergens transgress species
      borders and can be found in many plants or animals, some of them can even be
      detected in plants and animal tissues. Such proteins reveal a high grade of
      similarity in sequence and structure, which subsequently leads to immunological
      crossreactivity and according clinical syndromes.

PMID- 9012200
TI  - [Prevention of allergy].
AB  - The increase in prevalence and morbidity of allergic disease requires more
      employment of prevention strategies. The time of manifestation, severity and
      clinical course of atopic disease are primarily determined by genetic factors.
      TH1 and TH2 cell behaviour may in the future be used as predictors of atopy. A
      great number of environmental influences, like exposure to allergens and adjuvant
      trigger factors are modulating the clinical course. Sensible strategies of
      prevention in high-risk-families, as breastfeeding, hydrolysed hypoallergenic
      formula and maternal food avoidance during pregnancy or lactation are discussed.

PMID- 9012201
TI  - [Atopic dermatitis and food allergy in infancy and childhood].
AB  - Food allergies are causal factors for atopic dermatitis (AD) in 50% in infancy,
      in 20 to 30% in childhood, and only in 10 to 15% after puberty and in adulthood.
      Cow's milk, egg, fish, wheat, soy, nuts and citrus-fruits are the most proven
      allergens. Pseudoallergens, especially food-additiva, have to be regarded too.
      For the proof of the clinical relevance that food allergy is causing AD a
      positive result of elimination and provocation has to be required. When by these
      diagnostic procedure a special food is found as causing the AD it has to be
      eliminated in the diet of this patient. In severe cases of AD semi-elementary
      respectively few foods diets may be necessary. However in most cases of AD the
      "diet of choice" is an age related normal nutrition. To delay respectively to
      avoid the manifestation of atopy special recommendations for the nutrition of
      high risk newborns and infants (especially long breast feeding, late solid
      feeding) should be considered.

PMID- 9012202
TI  - [Bronchial asthma: extrinsic, intrinsic or mixed?].
AB  - The term "bronchial asthma" does not describe a single disease but a syndrome
      with similar symptoms but different etiology. The differences between the several
      manifestations of asthma have diagnostic, therapeutic and prognostic
      implications. According to clinical criteria atopic-allergic, intrinsic,
      occupational and mixed-type asthma can be differentiated. The separation into
      these different groups was initially based on clinical evaluation but is now
      supported by recent immunologic studies which have found basic differences as
      well as common features between these manifestations of asthma. To neglect this
      important diagnostic differentiation, as has been incorrectly proposed in recent
      years, will impair our understanding of the clinical appearance as well as the
      pathogenesis of asthma and can lead to inappropriate therapy.

PMID- 9012203
TI  - [Not all coughing is asthma--on differential bronchial asthma diagnosis in
      childhood].
AB  - Cough and wheezing are typical symptoms of asthma in childhood. But depending on
      age there are also other causes for the appearance of such complaints. A
      systematic approach to the differential diagnosis will clarify the situation in
      most of the patients.

PMID- 9012204
TI  - [Specific immunotherapy in allergies--evaluation of current status].
AB  - Specific immunotherapy is the treatment of choice in the therapy of inhalant
      allergies. Application route and dose regimen, selection and quality of
      allergens, as well as the individual patient represent different variables of
      immunotherapy to be considered. Premedication by oral antihistamines is mandatory
      for the reduction of side effects. Histamine-intolerance represents a
      contraindication for immunotherapy. Specific immunotherapy is highly efficacious
      leading to a 50-100% reduction of symptoms in nearly 90% of patients.

PMID- 9012206
TI  - [Amyotrophic lateral sclerosis].

PMID- 9012205
TI  - [Pseudo-allergies are due to histamine intolerance].
AB  - Numerous undesirable reactions to alcoholic beverages, foods, drugs and other
      substances are characterized by allergy-like signs and symptoms and yet show
      unambiguously negative allergy test results. Such persons should be assessed for
      evidence of histamine intolerance caused by histamine overload and/or diamine
      oxidase deficiency. Diamine oxidase is the main histamine degrading enzyme with a
      predominantly gut activity. This would explain why nutritional allergies are
      often primarily suspected. The clinical evidence for histamine intolerance is
      based on chronic headache, diarrhoea, vomiting, flush, urticaria, asthma-like
      symptoms, rhinitis and others. Histamine restricted food, supported if necessary
      by H1 antihistamine blockade are simple but highly efficacious measures as shown
      by us in large patient groups. Intolerance to red wine probably is the most
      outstanding clinical characteristic and a directed question must be included into
      any allergy history in order to avoid missing a very major diagnostic spectrum
      with good therapeutic maneuverability.

PMID- 9012207
TI  - [Clinical aspects of amyotrophic lateral sclerosis].
AB  - Amyotrophic lateral sclerosis is a progressive degenerative disease of upper and
      lower motor neurons with a prevalence of 4.3/100.000. The clinical symptoms
      include peripheral weakness and central spastic paresis and bulbar paralysis
      (weakness of mimic muscles, atrophy of the tongue, dysarthria). The prognosis
      leads to death within a few years. Pathogenetic factors are free O2-radicals, a
      disturbance of glutamate-metabolism, abnormal accumulation of neuronal proteins
      and autoimmunological mechanisms.

PMID- 9012208
TI  - [Medical intensive care aspects in treatment of amyotrophic lateral sclerosis].
AB  - Whereas it would be preferable to inform patients with amyotrophic lateral
      sclerosis (ALS) as early as possible about the possibilities of ventilatory
      support, not all of them are able to bear the required thorough information on
      the consequences of the diagnosis. The procedure therefore has to be
      individualized. Questionnaire studies have revealed, that in general patients
      hold the opinion that they themselves should decide, whether or not artificial
      ventilation should be applied. The non-invasive artificial home ventilation has
      led to advances in the management of patients with ALS, as a longer period of
      survival with a higher level of quality of life can be achieved. On the other
      hand, according to the author's opinion. Invasive artificial ventilation can not
      be the primary goal of medical support in the context of the prognosis
      (progressive differentiation). Much more this should focus on the appropriate
      steps to warrant increase of period of survival under conditions of at least
      minimal quality of life. Other opinions however have to be respected. Appropriate
      procedures for prevention and therapy of respiratory dysfunctions are discussed.

PMID- 9012209
TI  - [Patient education--support--help with decisions: ethical aspects in treatment of
      amyotrophic lateral sclerosis].
AB  - Patients with amyotrophic lateral sclerosis (ALS) develop progressive,
      degenerative loss of muscle function while retaining mental capacity. This
      implies special problems of patient information, which should be phase-adapted
      and patient centered. The difficult task of the physicians requires to provide
      sufficient information, to enable shared decision-making, without leaving the
      patient alone. Respiratory failure due to loss of muscle function is often the
      limiting problem. However, the possible option of ventilatory support opens the
      question when to stop treatment. It is most important to differentiate between
      intended mercy-killing and foregoing treatment due to the patient's wish.
      Discontinuation of treatment is morally justifiable, even required, if the
      patient refuses further treatment. Advance directives may be helpful to make
      decisions according to patients' preferences in time.

PMID- 9012210
TI  - [Legal limits of assisted death: exemplified by amyotrophic lateral sclerosis].
AB  - The article discusses the question to what extent the physician may offer aid in
      dying to the terminally ill patient. The author comes to the conclusion that the
      withdrawal of artificial ventilation (after application of anesthesia) is allowed
      and even a physician's duty if the patient refuses further ventilation. Because
      the competent patient may refuse treatment at any time, a doctor's willful
      disregard of his patient's right to self-determination could also be regarded as
      battery [section 110 Penal Code).

PMID- 9012211
TI  - [Spinal pathology in spinal muscular atrophy in comparison with amyotrophic
      lateral sclerosis].
AB  - We analyze neuronal cytopathology and secondary reactions in spinal-muscular
      atrophy (SMA) in comparison with amyotrophic lateral sclerosis (ALS). In a series
      of SMA and ALS cases, immunohistochemistry was performed on spinal cord sections
      for neuronal, astroglial and microglial antigens, ubiquitin and tau proteins.
      Swollen motoneurons staining for phosphorylated neurofilament proteins are seen
      in most SMA but few ALS cases. Ubiquitinated inclusions are found only in ALS. In
      SMA, glial bundles are prominent in anterior roots, to lesser extent in posterior
      roots. In ALS, glial bundles are seen only in some cases. While basic
      histopathologies are similar in both types of motor neurone diseases, neuronal
      cytoskeletal pathology is more prominent in SMA, possibly reflecting a more acute
      degenerative process. The presence of axon spheroids and glial bundles also in
      posterior horns/roots of both types of motor neurone disease suggests spread of
      degenerative pathology beyond the motor system.

PMID- 9012212
TI  - [Sporadic juvenile amyotrophic lateral sclerosis with neuronal basophil inclusion
      bodies--a nosologic entity?].
AB  - Among the very few cases of juvenile sporadic amyotrophic lateral sclerosis
      (ALS), 6 cases with neuronal basophilic inclusion bodies (BI) and clinical
      features uncommon to "classical" adult sporadic ALS have been reported. We
      present here two further cases and review the relevant literature. There are
      clinical and neuropathological similarities of systemic degeneration between
      juvenile cases with or without BI and juvenile and adult sporadic ALS when the
      latter is allowed to run a protracted course in patients on respirators. Because
      of overlapping topology and neuronal cytoskeletal pathology, the nosologic
      distinction within the ALS spectrum is questionable.

PMID- 9012213
TI  - [Ambulatory intensive therapy in the bulbar form of amyotrophic lateral
      sclerosis].
AB  - Due to the instability of their respiratory functions, patients suffering from
      ALS are potentially patients for permanent intensive care. The desire to provide
      care in the familiar environment at home on the one hand, and qualified
      professional support on the other hand, gives rise to the concept of ambulatory
      intensive care. This concept might be successfully implemented if one proceeds
      according to the motto: it is not the patient who is committed to technical
      facilities, but rather that the technical facilities ought to be committed to the
      patient. Home care, gastrostomy, tracheostomy, mobile suction drainage and the
      feasibility of home ventilation provide the groundwork for competent palliative
      medical care even in the bulbar form of ALS. Home care of such patients would be
      enhanced in terms of both security and quality if it were possible to have
      regular ambulatory check of the vital functions at intensive care units. In
      emergency cases, once their respiratory functions are stabilized patients could
      be discharged into home nursing after a short-term stay at the intensive care
      unit. Ambulatory intensive therapy would both serve to ease the burden of
      intensive care units in terms of costs and personnel, and to improve the life
      quality of patients.

PMID- 9012214
TI  - [Magnetic resonance tomography of the brain in amyotrophic lateral sclerosis].
AB  - We compared the magnetic resonance imaging results of 15 patients suffering from
      amyotrophic lateral sclerosis (ALS) with those of 30 age-matched controls to
      search for disease specific cerebral abnormalities. Symmetric hyperintensity
      along the corticospinal tract on the proton density spin-echo sequence was
      exclusively found in 4 ALS patients. It was associated with younger age, rapid
      disease progression and evolution of symptoms starting in the lower extremities.
      Signal loss of the motor cortex on T2-weighted images was frequently seen in ALS
      (9 patients) but was also observed in controls. As MRI is capable of providing
      direct evidence for ALS besides excluding other diseases it should be included in
      the diagnostic work-up of these patients.

PMID- 9012215
TI  - [Multifocal motor neuropathy with conduction block--a clinico-neuropathologic
      case report].
AB  - Descriptions on patients with multifocal motor neuropathy with conduction block
      (MMNCB), including histology, nerve fiber teasing and electron microscopy on
      nerve biopsy, are rare. We report a 64-year old female patient with progredient
      weakness of the upper extremities without sensory deficit. Electrophysiology
      shows conduction blocks up to 80% in several examined motor nerves. A biopsy of
      the sensory sural nerve reveals features of a mixed axonal and de- and
      remyelinating neuropathy. Thus sural nerve biopsy contributes here significantly
      to differential diagnosis and supports an immune mediated pathogenesis of MMNCB.

PMID- 9012216
TI  - [Sleep apnea in myasthenia gravis].
AB  - 19 middle-aged patients with myasthenia gravis (MG) and 10 age-matched controls
      underwent overnight polysomnography and neuropsychological testing, in order to
      assess the frequency, degree, type and risk factors of sleep apneas in MG and to
      show their influence on sleep profile and neuropsychological variables. We
      observed in 60% of the myasthenics, low grade central type of sleep apneas and
      hypopneas with resulting oxygen desaturations, occasionally occurring during REM
      sleep without influence on sleep profile and vigilance but resulting in
      significant memory impairment. The only found risk factor for the development of
      sleep apneas was age.

PMID- 9012217
TI  - [Lactate determination at rest and during bicycle ergometry in healthy probands
      and in patients with mitochondrial myopathies].
AB  - Measuring lactate during moderate exercise is a useful tool in the diagnosis of
      mitochondrial disorders. It was the aim of this study, to develop reference
      limits for lactate at rest, during exercise and after the exercise. We
      investigated 18 healthy subjects and 6 patients with a mitochondrial disorder. In
      controls, serum lactate levels were comparable to already reported findings. In 4
      patients lactate levels were markedly increased during the exercise. Measurement
      of serum lactate is a simple and useful step in the diagnosis of mitochondrial
      disorders.

PMID- 9012218
TI  - [Heart muscle involvement in myopathies].
AB  - By means of a comprehensive cardiologic examination "definite" cardiac
      involvement was found in 71% of patients with myotonic dystrophy (MD). In 50% of
      patients with Becker's muscular dystrophy (BMD) and in 70% of patients with
      mitochondrial myopathy (MMP). "Equivocal" cardiac involvement was found in 21% of
      patients with MD, in 50% of patients with BMD and in 20% of patients with MMP.
      The correlation between cardiac involvement and the neurological deficit was
      weak.

PMID- 9012219
TI  - [Innovative respiratory muscle training for patients with Duchenne muscular
      dystrophy--a psychological evaluation].
AB  - For neuromuscular patients with progressive respiratory muscle weakness a new
      training apparatus was developed, which allows a home training of strength as
      well as endurance of the inspiratory muscles, especially the diaphragma. A
      significant positive training result could be proved in a comparative study
      between 2 groups of 15 Duchenne muscular dystrophy (DMD) patients each (8). By
      the end of the training the satisfaction of patients with the new training
      equipment was evaluated by means of a questionnaire. The degree of satisfaction
      was determined at a 10-point scale. Critical ideas were used for improvement of
      the newly developed training apparatus.

PMID- 9012220
TI  - [In vitro transformation of amniotic cells to muscle cells--background and
      outlook].
AB  - DNA analysis of peripheral blood leucocytes is routinely used to demonstrate
      mutations in the dystrophin gene in patients with Duchenne's muscular dystrophy.
      In approximately 35% of patients. DNA studies are not informative; in these
      patients immunochemical analysis of a muscle-biopsy specimen can determine
      whether dystrophin, the protein product of the gene for Duchenne's dystrophy, is
      absent. DNA analysis can be performed in amniocytes for the prenatal diagnosis;
      immunochemical testing for dystrophin cannot be performed because the protein is
      not expressed in these cells. To circumvent this limitation in prenatal
      diagnosis, we induced myogenesis in amniocyte cultures by addition of a
      rhabdomyosarcoma's cell line supernatant. Rhabdomyosarcomas are tumors of
      skeletal muscle and known to produce myogenic factors. After 6 weeks skeletal
      muscle proteins could be detected in 10 amniocyte cultures. Cultures from fetuses
      with no family history of Duchenne's dystrophy expressed dystrophin, cultures
      from patients with Duchenne's dystrophy were dystrophin-deficient. Immunochemical
      analysis of dystrophin in genetically altered non-muscle cells may be applicable
      to the prenatal diagnosis of Duchenne's muscular dystrophy when conventional DNA
      analysis is not informative.

PMID- 9012221
TI  - [Blood alcohol concentrations after oral alcohol administration--effect of age
      and sex].
AB  - Blood concentrations following oral ingestion of ethanol are lower than after
      intravenous injection, currently explained by first pass metabolism of ethanol in
      the stomach, which depends among others on the activity of gastric alcohol
      dehydrogenase. Since this has been shown to be different in various groups of
      subjects it was intended to examine the influence of age and gender on
      concentrations and elimination rates of ethanol after oral administration.
      Following the ingestion of 0.3 g ethanol/kg body weight blood concentrations in
      24 volunteers (six mother daughter- and six father son pairs) were determined. 30
      and 60 min after ingestation blood ethanol concentrations were significantly
      higher in the elderly as compared to the younger, but there was no difference
      between female and male subjects. The ethanol elimination rates of the four
      groups showed no significant difference. As known from other studies the activity
      of gastric alcohol dehydrogenase in women is significantly lower as compared to
      men; so that higher blood ethanol concentrations had to be expected. Thus the
      results support indirectly the hypothesis that gastric first pass metabolism is
      not only influenced by the activity of gastric alcohol dehydrogenase. Other
      possible determinants are discussed. Significant higher blood ethanol
      concentrations after ethanol ingestion in the elderly have to be considered for
      example with respect to driving ability.

PMID- 9012222
TI  - [Preparation for colonoscopy: a reliable and easily implemented regimen].
AB  - Three different colonoscopy preparation methods were tested in 150 out-patients
      who received colonoscopies, 50 in each group, a randomized prospective simple
      blind study. The original Golytely-recepture with three litres of liquid was
      tested against Clean Prep which has to be dissolved in four litres of liquid.
      Both receptures had the same isotonic salt solutions. The third group was a
      method with a laxans (X-Prep) including eating restriction lasting three days.
      The judgment criteria were the cleanliness of the bowel, the formation of foam
      and the subjective sensitivity of the patient during the preparation phase. The
      preparation with the three bags containing three litres of Golytely solution
      according to the original recepture proved to be the least troublesome for the
      patients and was the most efficient method when it came to cleanliness and the
      formation of foam. The costs of this preparation methods were lower than those of
      the other methods.

PMID- 9012223
TI  - [Libyan patient with chronic diarrhea].
AB  - A 22-year-old Libyan patient suffering from chronic diarrhea presented with an
      alpha-heavy chain paraprotein and a lympho-plasmacellular lymphoma infiltration
      of the duodenal mucosa. These findings supported the diagnosis of
      "immunoproliferative small intestinal disease" (IPSID). In this disease, that
      occurs almost solely in countries with low socioeconomic status, a diffuse
      infiltration of small intestinal mucosa by neoplastic lymphoid cells causes
      chronic malabsorption. About 65% of patients exhibit a paraprotein in serum,
      urine or jejunal juice that consists of the heavy chain of immunoglobulin A
      (alpha-heavy chain). In advanced stages, IPSID resembles histologically and
      clinically high grade lymphoma: some patients develop masses in the gut wall, an
      abdominal lymphadenopathy and involvement of other organs including bone marrow.
      The disease is believed to be triggered by a chronic infectious antigenic
      stimulus. Thus, in early stages in some patients cure may be achieved by
      antibiotic therapy alone. In advanced disease, chemotherapy including
      anthracyclins is necessary.

PMID- 9012224
TI  - [Osteomyelitis sicca in Crohn disease--coincidence or extraintestinal
      manifestation?].
AB  - In patients with Crohn's disease arthritis of the large joints, osteomalacia,
      osteoporosis and aseptic bone necrosis as a consequence of malabsorption and
      glucocorticoid intake may occur. The case of a patient with long-standing Crohn's
      disease is presented who subsequently developed abacterial osteomyelitis of the
      jaw ("osteomyelitis sicca"). The symptoms of the osteomyelitis improved under
      immuno-suppressive therapy. Because the etiopathogenetic concepts for Crohn's
      disease and osteomyelitis sicca are similar, the latter could be a rare
      extraintestinal manifestation in Crohn's disease, not described previously.

PMID- 9012225
TI  - [Psychosocial factors in Crohn disease--an overview].
AB  - In more than 50 years of psychosomatic research on Crohn's disease, several
      research hypotheses have been generated, which are critically reviewed here: A
      disease-specific personality could never be identified, and an important role of
      psychiatric and psychopathologic personality traits in disease onset was never
      substantiated. Moreover, most abnormalities found in psychological tests have to
      be regarded as secondary to chronic illness. Effects of psychologic and social
      stress on symptoms have not been validated, but it may be that Crohn's patients
      may have developed less coping abilities with daily hassles. Psychotherapy may
      improve this, but does not affect the clinical course of the disease.

PMID- 9012226
TI  - [Is there a value to biopsies of normal colonic mucosa in unexplained diarrhea?].

PMID- 9012227
TI  - [Does mucosal immune reaction to nutritional antigens play a role in certain
      neurologic diseases? Studies exemplified by gluten hypersensitivity].

PMID- 9012228
TI  - [Endovascular surgery].

PMID- 9012229
TI  - [Vascular stents and development of endoluminal therapy of aortic aneurysm].
AB  - Intravascular stents have played an important role in improving early and long
      term patency in the treatment of arterial occlusive disease, particularly in the
      iliac arteries after failed balloon angioplasty. The development of covered
      stents opened a new dimension for non-operative therapy of aneurysmal disease.
      Transluminally placed stent-grafts represent a blending of technologies with use
      of intravascular stents and prosthetic vascular grafts. Stent-graft combinations
      were first envisioned by Dotter in 1969 as devices that would ultimately be
      useful to treat aneurysms, pseudoaneurysms and arterio-venous fistulas. Animal
      studies of endovascular stented grafts demonstrated the potential feasibility of
      these devices to treat arterial lesions. Parodi et al. first implanted stent
      grafts in patients with abdominal aortic aneurysms and demonstrated its clinical
      feasibility. Newly developed stent-grafts allowed to treat successfully a limited
      number of patients with AAA. Although much has been reported about the healing
      properties of prosthetic grafts in extraluminal locations, there are only little
      data concerning the arterial response to a prosthetic graft placed within the
      lumen or anchored into the wall of a human vessel. Therefore, long-term
      evaluation of these new devices will be crucial.

PMID- 9012230
TI  - [Infrarenal abdominal aortic aneurysm: morphological classification as decision
      aid for therapeutic procedures].
AB  - This clinical trial aimed to prospectively investigate the morphological
      structure of infrarenal abdominal aortic aneurysms (AAA) to establish a valid
      dataset in the preoperative assessment supporting either the conventional or
      endovascular (TPEG) surgical approach. Regarding both the general feasibility
      testing and safe TPEG placing, all the anatomic AAA data must already be measured
      preprocedurally, due to the necessity for conversion as a frequent consequence of
      an intraprocedural failure. Between January 1993 and June 1995, all the patients
      (n = 159) admitted for elective AAA repair, were prospectively analysed. Graded
      on the basis of these measurements we developed a new AAA classification system
      supporting the kind of the surgical procedure (standard) approach vs. TPEG).
      Three different types of AAA were clearly defined. Due to morphological AAA
      criteria, 86 out of 159 patients (54.1%) might be suitable for TPEG (Type I, IIA
      and IIB). An infrarenal (proximal) neck < 15 mm, an infrarenal aortic diameter >
      24 mm or an extension of the aneurysm to the iliac bifurcation are considered to
      be exclusion criteria for TPEG placement. In consideration of relevant co
      morbidities (e.g. renal artery stenosis, SMA occlusion, iliac occlusive disease,
      simultaneous operations) only 43 out 159 patients (27.1%) were good candidates
      for TPEG. In general, smaller AAA are more appropriate for TPEG repair due to
      better proximal and distal fixation. As a consequence, indication criteria for
      AAA repair must not be expanded to smaller AAA.

PMID- 9012231
TI  - [Initial clinical experiences with endovascular stent-grafts for treatment of
      infrarenal abdominal aortic aneurysm].
AB  - With a series of 34 transluminal stent-graft procedures, we assessed the
      feasibility and clinical effectiveness of a new stent-graft for the treatment of
      infrarenal abdominal aortic aneurysms (AAAs). We treated 34 male patients (mean
      age 71 years) with straight of bifurcated nitinol stents covered with woven
      Dacron graft material for infrarenal excentric saccular AAA (n = 3) or AAA
      involving the bifurcation and the common iliac arteries (n = 31). The 18-F
      delivery system was advanced via a surgical arteriotomy and the stent-graft was
      placed under fluoroscopic control. Follow-up period ranged from 8 days to 13
      months. The implantation of the stent-grafts was technically successful with
      exclusion of AAA in 31/34 cases (91%). In 2 patients, there was a persisting leak
      at the distal end of the endoprosthesis after treatment; in another, marked
      coiling of the external iliac artery impeded the delivery system to be advanced
      and consecutive rupture resulted in conversion to surgical repair. Other
      procedure-related complications were acute hepatic failure due to gastric
      bleeding in a patient with liver cirrhosis, graft occlusion due to emboli
      originating from the left atrium (n = 1), local hematoma (n = 1), and AV-fistula
      (n = 1) requiring surgery. A post-implantation syndrome with leucocytosis and
      elevated C-reactive protein was observed in all patients. Endoluminal repair of
      infrarenal AAA with use of Dacron covered nitinol stent-grafts is feasible, safe
      and clinically effective. However, careful long-term evaluation is necessary
      before it will become clinical practice.

PMID- 9012232
TI  - [Difficulties and complications in transfemoral implantation of stent prostheses
      in infrarenal abdominal aortic aneurysms].
AB  - Between August 31st, 1994 and January 31st 1996, 69 patients received
      transfemoral application of stentgrafts for treatment of AAA. Only 10 patients
      received tube grafts in contrast to 59 bifurcated grafts, which were assembled
      within the aortic lumen. All aneurysms were symptomatic, growing or sacciform.
      Risk factors seemed to be aggravated in comparison to conventional operations. 59
      operations were technically successful, three were converted to open laparotomy,
      because of technical malfunction twice and misplacement once. 5 postoperative
      deaths occurred from multiorgan failure. 7 patients were discharged with primary
      persisting leakage. All patients exhibited reactions to the stentgraft
      deployment, which mainly referred to the clotting system and/or arterial
      pressure. Postoperatively nearly all patients presented a "post-implantation
      syndrome" over days up to 4 weeks. The observed difficulties and complications
      can be attributed in part to a "learning curve", in part to difficult anatomic
      situations, which we included in our series. During follow up at 3, 6 and 12
      months 7 secondary leakages were observed, three times because of a documented
      desintegration, once because of suspected beginning desintegration at a stent
      graft junction, and three times because of possible failure of graft material.
      The leakages could be repaired by interventional procedures.

PMID- 9012233
TI  - [Results of surgical treatment of acute traumatic aortic rupture].
AB  - Between 1967 and 1994 48 patients have been treated at our institution for acute
      rupture. Two patients died before operation, in two cases the operative attempt
      had to be abandoned with irreversible cardiopulmonary arrest, and in 44 patients
      surgical correction could be performed, The rupture was complete in 14 cases and
      incomplete in 30. In 25 patients surgery consisted of direct suture, in one
      patient an aortoplasty was performed, and in 18 patients a dacron tube
      interposition was necessary. In 7 cases the clamp and repair technique was
      applied, and in 37 cases extracorporeal circulation was installed. The hospital
      mortality amounted to 18% and was mainly contributable to the concomitant
      injuries. Two patients presented with paraplegia at admission, both died;
      postoperative paraplegia occurred in two instances, once after 48 hours. The late
      results were in the majority of the cases influenced by orthopedic or
      neurological sequelae, only one patient had to be reoperated for a false
      aneurysm. Our results and the review of the literature lead to the following
      conclusions: In spite of an optimized emergency care system, many patients with
      aortic rupture die before any surgical intervention. The installation of
      extracorporeal circulation can decrease the incidence of postoperative
      paraplegia; in our experience the administration of heparin does not increase the
      risk of bleeding from concomitant injuries. Direct suture represents the
      correction of choice. The long-term results are excellent.

PMID- 9012234
TI  - [Delayed surgical therapy of acute aortic rupture].
AB  - Immediate surgical treatment of traumatic aneurysms of the aorta is in our point
      of view in most cases problematic, also because of the combination with life
      threatening injuries of other organ systems. In our own patient-collection seven
      patients out of 44 with traumatic transsection were immediately operated. Six
      patients died in tabula, three of them due to uncontrollable hemorrhage. An
      analysis of over 5,000 post mortem findings from the department of forensic
      medicine in Hamburg revealed that injuries of the aorta lead in 98.3% to death in
      the first two hours after the accident. This shows that only a small number of
      injured victims survive. The danger of a two stage rupture is judged differently.
      We did not observe this problem in the patients with aortic lesion following
      blunt chest trauma and stable conditions who had first undergone treatment for
      other injuries and therefore operated in the interval period after two to ten
      weeks. With this strategy the lethality involving surgical management of aortic
      injuries in our unit decreased to 13%.

PMID- 9012235
TI  - [Surgical therapy of chronic traumatic aortic aneurysm].
AB  - Rupture of the aorta that usually occurs with major blunt trauma of the chest is
      associated with a high mortality, and only 2% of the patients survive long enough
      to develop a false aneurysm. Although symptom-free latent period is not rare,
      there is evidence of progression. Since 1970 we operated on 28 patients (24 male
      and 4 female, mean age 41.2 years) for chronic traumatic aneurysm of the
      descending aorta. A previous blunt trauma of the chest had certainly occurred in
      23 cases (3 months to 20 years before) and was likely in 4 patients; in one young
      woman the aneurysm developed after percutaneous angioplasty of a coarctation. In
      26 patients surgical repair consisted in a Dacron tube interposition, and in 2
      cases patch repair was adequate. In 11 cases the "clamp and repair" technique was
      applied, while in 17 patients extracorporeal circulation was established to
      perform the reconstruction, two of these cases were operated with hypothermic
      circulatory arrest. Although there was no correlation between the occurrence of
      complications and the applied procedure, we lately turned to establish
      cardiopulmonary bypass in all cases with regard to a better control of the
      hemodynamics during clamping, the possibility of direct retransfusion of blood,
      and the option to extend the procedure, if necessary. In view of the facts, that
      traumatic thoracic aneurysms develop late complications in about 75% of the
      cases, and the morbidity in elective surgery is of a low figure, we conclude,
      that surgery of such lesions is mandatory, once the diagnosis has been
      established, and that an expectant attitude in the treatment is justified only in
      exceptional cases.

PMID- 9012236
TI  - [Femoropopliteal vascular replacement: vein, ePTFE or ovine collagen?].
AB  - In an eight year-period from 1988 to 1995 653 femoropopliteal and femorocrural
      bypasses were performed. 347 above-knee reconstructions 206 below-knee
      reconstructions and at last 100 femorocrural bypasses were analysed. The
      cumulative patency rate after a follow up of three years for above-knee vein
      bypasses was 90%, patency rate for PTFE grafts in the same period was 52%, for
      ovine collagen grafts 56%. For below-knee bypasses with autologous saphenous vein
      a function rate of 76% could be observed in the same period, the rate of PTFE
      grafts in this position was only 30%. In this position 3-year patency rates of
      50% were achieved with ovine collagen grafts. This difference was statistically
      significant. Three years cumulative patency rate for femorocrural reconstructions
      with greater saphenous vein was 72%, the function rate for PTFE in this position
      was below 30% after a follow up of one year, with ovine grafts below 40%. Graft
      infection, aneurysm formation and postoperative mortality were low in all groups.
      Our data demonstrate, that patency rates of autologous vein bypasses could not be
      achieved with PTFE or ovine collagen prosthesis in any femoropopliteal the
      femorocrural position. We therefore cannot confirm the recommendation to use
      alloplastic grafts as primary choice for above knee bypasses to spare the
      saphenous vein.

PMID- 9012237
TI  - [Clinical experience with a new antimicrobially coated InterGard-IgK/AM vascular
      prosthesis in surgical treatment of deep wound infection with involvement of the
      synthetic bypass: report of 2 cases].
AB  - We report 2 cases of infected vascular prosthesis, where the infected alloplastic
      material was removed and the revascularisation of the lower extremity was done by
      implantation of the new antimicrobial surface-coated InterGard prosthesis in the
      area of the former infected graft. An extra-anatomical bypass was not promising
      in these cases. Clinical, bacteriological and granulocyte-scintigraphic
      examinations have provided no evidence for persisting infection 12 and 11 months
      after implantation of this prosthesis. We are aware that the postoperative
      observation periods are too short to allow definitive assessment. Nevertheless we
      still consider that this prosthesis means a new and promising option in the
      treatment of infected vascular graft.

PMID- 9012239
TI  - ["The Stent Summit", 30-31 May 1996 in London].

PMID- 9012238
TI  - [Controlled reperfusion of the extremities for preventing local and systemic
      damage after prolonged ischemia. An experimental study with the swine model].
AB  - Our previous studies in isolated rat hindlimbs using crystalloid perfusion
      solutions have shown that control of the initial reperfusion reduces postischemic
      complications. However, no experimental study has been undertaken to evaluate the
      concept of controlled limb reperfusion experimentally in an in-vivo blood
      perfused model and to assess the local as well as systemic effects of normal
      blood reperfusion and controlled limb reperfusion. Of twenty pigs undergoing
      preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5
      hours and served as controls. Fourteen other pigs underwent 6 hours of complete
      infrarenal occlusion. Thereafter, embolectomy was stimulated in 8 pigs by
      removing the aortic clamp and establishing normal blood reperfusion at systemic
      pressure. In 6 other pigs, control of the composition of the reperfusate and
      control of the conditions of reperfusion was done during the first 30 min,
      followed by normal blood reperfusion. Six hours of infrarenal aortic occlusion
      lead to a severe decrease in high energy phosphates and muscle temperature and a
      slight increase in creating kinase (CK) and potassium in the systemic
      circulation. Normal blood reperfusion resulted in severe reperfusion injury:
      massive edema developed (80.6% vs. 76.6%, p < 0.0009), the tissue showed a marked
      decrease in oxygen consumption (7.3 +/- 1.1 vs. 14.3 +/- 2.5 mL )2/100 g/min, p <
      0.02), glucose consumption (0.19 +/- 0.06 vs. 0.51 +/- 0.03 mg/100 g/min, p <
      0.06), tissue ATP (18.3 +/- 1.9 vs. 36.1 +/- 0.9 mumol/g protein, p < 0.000001),
      total adenine nucleotides (26.3 +/- 2.6 vs. 45.8 +/- 1.5 mumol/g protein, p <
      0.00001), muscle pH (5.9 +/- 0.1 vs. 7.3 +/- 0.1, p < 0.000006) and total calcium
      in the femoral vein (2. +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, p < 0.002). Furthermore,
      a massive increase was seen in CK concentration (12,743 +/- 2,562 vs. 513 +/- 80
      U/L, p < 0.0003), potassium (7.9 +/- 0.3 vs. 4.4 +/- 0.2 mmol/L, p < 0.000001)
      and muscle rigidity (60 +/- 11 vs. 122 +/- 1 degree, p < 0.00008). In sharp
      contrast, initial treatment of the ischemic skeletal muscle by controlled limb
      reperfusion resulted in normal water content (77.6 +/- 0.4 vs. 76.8 +/- 0.3%),
      oxygen consumption (13.2 +/- 1.6 vs. 14.9 +/- 3.2 mL O2/100 g/min), glucose
      consumption (0.58 +/- 0.18 vs. 0.46 +/- 0.11 mg/100 g/min), flow (5.4 +/- 1.1 vs.
      4.6 +/- 4.6 +/- 0.5 mL/100 g/min) and muscle rigidity (106 +/- 4 vs. 122 +/- 1
      degree). Furthermore, controlled limb reperfusion resulted in higher total
      adenine nucleotides content (78% vs. 57% of control), less tissue acidosis (6.6
      +/- 0.2 vs. 5.9 +/- 0.1, p < 0.002), severely reduced CK release (2,618 +/- 702
      vs. 12,743 +/- 2.562, p < 0.02) and potassium release (5.1 +/- 0.3 vs. 7.9 +/-
      0.3 mmol/L, p < 0.0002) as compared to normal blood reperfusion. In conclusion
      this study shows that 6 hours of acute infrarenal aortic occlusion will result in
      a severe reperfusion injury (postischemic syndrome) if normal blood at systemic
      pressure is given in the initial reperfusion phase. In contrast, initial
      treatment of the ischemic skeletal muscle by controlled limb reperfusion reduces
      the metabolic, functional and biochemical alterations.

PMID- 9012240
TI  - [Forgotten Dresden Surgeons (I)].
AB  - This article describes problems some surgeons of Dresden were confronted with in
      the time between 1750 and 1850. These surgeons present the transition of the 'Age
      of Enlightment' and the period of sciences. Special achievements are mentioned:
      Hedenus as the founder of the modern surgery in Dresden and as a pioneer in
      practising the operations of glandula thyreoidea, Ohle, Meding, Pech and Graeffe
      mainly as military surgeons and surgery teachers, Ammon as a plastic surgeon and
      Andree as a dental surgeon.

PMID- 9012241
TI  - [Quality assurance in surgery].

PMID- 9012242
TI  - [The detection of toxinogenic Bacillus cereus strains].
AB  - Investigations into optimal culture conditions for Bacillus cereus in order to
      detect bacterial toxins in a cell culture system showed that Dulbecco's modified
      Eagle's medium supplemented with 5% fetal calf serum is the medium best suited
      for this purpose. The highest toxicity levels were seen when bacteria were
      cultured at 21 degrees C. In 42 of 43 Bacillus cereus-strains isolated from milk
      and milk products, toxin formation was detected using the MTT-test. In 11
      strains, toxin formation was even shown when bacteria were cultured at 4 degrees
      C. When culture supernatants were examined in a commercially available ELISA, all
      cytotoxic strains were shown to form diarrheal toxin.

PMID- 9012243
TI  - [The current diagnosis and classification problems of mental diseases].
AB  - Both international (ICD-9, ICD-10) and national classifications were used as the
      examples for establishing the connection between the methodology of diagnosis and
      creation of systematics of mental diseases. The thesis was formulated that the
      creation of the national classification well grounded scientifically is to
      reflect main traditions and tendencies of Russian and world psychiatry.

PMID- 9012244
TI  - [The assessment of the efficacy of the rehabilitation of patients with the
      sequelae of stroke].

PMID- 9012245
TI  - [Central pain].

PMID- 9012246
TI  - [Neuronal molecules of cellular adhesion (their structure, functions and the
      clinico-diagnostic prospects)].

PMID- 9012247
TI  - [The pathokinesis of vascular brain lesions].
AB  - Pathokinesis as the chain reaction included development and self-regulation of
      pathological processes which manifested themselves by different forms of
      cerebrovascular pathology was analysed basing on 5-year follow-up of 200 patients
      with initial forms of cerebrovascular deficiency and examination of patients with
      discirculatory encephalopathy (in 100 of them stroke had developed during this
      time) as well as the data on 873 patients with stroke. Pathokinetic significance
      of risk factors, conditions predisposing to stroke development and stroke direct
      reasons are characterised as well as therapy of different intensity. The
      possibilities of the correction of some pathokinetic mechanisms by means of
      emergent therapy as well as the role of some uncorrectable factors (biological
      and situational ones) were defined too. The pathokinetic peculiarities of the
      main forms of insult were defined more precisely in relation to on the degree of
      individual compensatory abilities.

PMID- 9012248
TI  - [Cerebrovascular reactivity in the pathogenesis of ischemic brain lesions in
      patients of different ages].
AB  - Cerebrovascular indices (cerebrovascular reactivity, plethora of pulse, the
      degree of atherosclerotic damage of carotids) were evaluated in 445 patients with
      either transient disturbances of brain's circulation or ischemic stroke. The
      patients' age was 32-85 years. It was found that the alterations in the system of
      neurogenic regulation which were the consequences of some pathogenic factors'
      influence (infectious diseases, closed brain's trauma, latent intoxication),
      resulted in some cases in formation of lower level of cerebrovascular reactivity
      which in turn was one of the reasons of ischemic cerebral disorder development.
      Further influence of such factors as atherosclerosis, increase of blood
      coagulability, decrease of total arterial pressure may result in alterations in
      cerebrovascular system's stability and in development of cerebrovascular diseases
      at younger age.

PMID- 9012249
TI  - [Proton magnetic resonance spectroscopy in transient disorders of the cerebral
      circulation].
AB  - Proton magnetic resonance spectroscopy of the brain was performed in 8 patients
      with asymptomatic carotid stenosis as well as in 26 patients with transient
      ischemic attacks (TIA) and 19 patients with reversible ischemic neurologic
      deficiency (RIND). The study was carried out by means of Philips apparatus. The
      results of investigation were compared with data of spectroscopic examination of
      9 older and 10 younger normals. The mathematical analysis of ratio of N
      acetylaspartate concentration (NAA) to phosphocholine (Pch), phosphocreatine
      (Pcr), and lactic acid was used to describe the metabolic changes. As a result
      lactic acid was not found in control volunteers' brains while it was detected
      either in the damaged (59%) or in the contralateral (47%) hemispheres of the
      patients. The significant decrease of NAA/Pch and NAA/Pcr ratios was observed in
      the pathological hemispheres of the patients. These results testify to high
      sensitivity of proton magnetic resonance spectroscopy for evaluation of metabolic
      disturbances in latent or reversible cerebral ischemia.

PMID- 9012250
TI  - [The late sequelae of radiation exposure on the nervous system].
AB  - Clinical, neuropsychologic, neurophysiologic as well as neuromorphologic (in
      legal cases) examinations of Chernobyl liquidators were performed. In addition,
      the study was made of the monkeys exposed to 1,5 Gy radiation. The results
      obtained testified to the organic character of cerebral damages. They may be
      characterised as chronic progressive discirculatory-hypoxic syndrome in which
      disorders of vascular permeability were expressed and dystrophic destructive
      irreversible alterations of nervous cells occurred.

PMID- 9012251
TI  - [Mental disorders in the participants in the cleanup of the aftermath of the
      accident at the Chernobyl Atomic Electric Power Station].
AB  - 320 persons Chernobyl liquidators were examined. The selection was made on the
      basis of presence of mental disturbances of nonpsychotic level. Five syndromes
      were revealed: astheno-neurotic (116 cases), astheno-depressive (92 cases),
      obsessive-phobic (57), astheno-hypochondriac (32), hysteric-hypochondriac (23
      persons). The structure of above-mentioned syndromes was determined by
      combination of different symptoms (there were 40 symptoms). It was found that
      affective disorders of depressive spectrum are prevalent in all mental
      manifestations, while vasovegetative disturbances were common in psychosomatic
      manifestations.

PMID- 9012252
TI  - [The psychopathological characteristics of the family status of schizophrenia
      patients].
AB  - Family and parenteral relations were investigated in 196 schizophrenic patients
      during 7-12 years. In was confirmed that lonely individuals prevailed among the
      schizophrenic patients. Psychopathological peculiarities of motivations of
      beginning, preservation and cessation of marriage were analysed. The distinctive
      signs of heterosexual activity of patients in marriage as well as their relations
      in such pairs as "mother-child", "father-child" were also recorded. It was
      established that with aggravation of psychopathological disturbances the
      differences from corresponding demographic indices in normal population became
      more pronounced and social disadaptation more expressed.

PMID- 9012253
TI  - [Forensic psychiatric expertise in brain tumors].
AB  - The patients with brain tumors are quite rare in forensic-psychiatric practice.
      The authors observed only 21 cases during 25 years (that is 0.05% from all the
      persons subjected to the forensic-psychiatric examination). The tumors were
      revealed in 11 patients during examination; 10 patients underwent forensic
      psychiatric examination after operation for brain tumor. There were different
      mental disturbances of various degree in such patients: disorders of memory,
      emotional instability, impulsivity, disorders of consciousness, phenomena typical
      for epileptiform syndrome, and other disorders. 16 patients were characterised as
      irresponsible ones. The supervision of neurologist and psychiatrist was
      recommended in all cases.

PMID- 9012254
TI  - [The use of hyperbaric oxygenation in treating mental patients resistant to
      psychopharmacotherapy].
AB  - 127 patients were observed: 65 schizophrenic patients and 62 patients with
      vascular mental disorders. The treatment by hyperbaric oxygenation (HBO) was
      applied in such patients to overcome resistance to psychopharmacotherapy. A
      positive clinical effect was marked in 72.5% of cases (in 67.4% of schizophrenic
      patients and in 77.4% of patients with vascular diseases). The conclusion was
      made that HBO enabled to shorten the time of hospital treatment as well as to
      improve both clinical and social prognosis.

PMID- 9012255
TI  - [The prevention of acute disorders of cerebral circulation: the theory and the
      reality].
AB  - It would be valid to conduct prophylaxis of acute cerebrovascular disturbances
      (ACVD) in the context of state integral program of prophylaxis of the main
      noninfectious diseases. Its basic principles are: control of risk factors,
      integral approach and priority of populational strategy. The main medical
      directions of ACVD prophylaxis are: control of arterial hypertension and
      prevention of cardioembolic insult in patients with heart rhythm disorders. It is
      also possible to prevent repeated ACVD in patients with transitory ischemic
      attacks and minor insults. The best result is prognosed in combination of the
      state policy of providing the healthy mode of life of population and medical
      prophylaxis of ACVD in high risk groups.

PMID- 9012256
TI  - [The efficacy and mechanisms of action of lerivon in alcoholism].
AB  - Clinico-biological examination of 50 alcoholic patients was carried out. 30
      patients were treated with lerivon (L) during 1 month. 15 control patients
      received amitriptylin for 1 month and 15 patients received relanium for 7 days.
      It was determined that L was quite effective in treatment of depression in
      alcoholic patients. The main L effects were anxiolytic, antidepressive and
      hypnotic. The drug also decreased alcohol addiction, had vegetostabilising and
      sedative effects. The conclusion was made on pathogenetic action of L in
      alcoholism: It influences upon dopaminergic mediation in catecholamine system.
      Administration of L permitted to normalize neurochemical processes underlying
      alcohol addiction and depression. L was well tolerated. Side effects
      complications, drug addiction were not registered.

PMID- 9012257
TI  - [Endaural reflex diagnosis of cochleovestibular dysfunctions in patients with
      vascular brain diseases].
AB  - The analysis of electrical conductivity of acupuncture points was performed in
      225 patients with cochleovestibular dysfunctions against a background of
      cerebrovascular pathology. Original highly sensitive express-method with
      application of special registering device was proposed for endaural reflex
      diagnosis. The system was elaborated for interpretation of examination's results.
      It permitted either to confirm or to define more precisely both the location
      (side and level) and the stage of cochleovestibular damage.

PMID- 9012258
TI  - [The constrictive reactions of the cerebral vessels in the pathogenesis of
      circulatory encephalopathy].
AB  - Cerebral vasoconstrictive reactions were analysed in 100 healthy men and 165
      patients with atherosclerotic discirculatory encephalopathy (DE) of stage I and
      II. The study was performed by means of functional loading tests such as
      antiorthostatic, hyperventilation, with psychoemotional tension. Individuals with
      hyperconstrictive reactions were revealed both among healthy persons and among
      the patients. These reactions manifested as cerebrovascular hypertonicity or
      decrease of cerebral blood flow. The frequency of hyperconstrictive reactions as
      well as their registration by means of several functional tests such
      significantly increased with DE progression.

PMID- 9012259
TI  - [The level of autoantibodies to glutamate receptors in the blood serum of
      patients in the acute period of ischemic stroke].
AB  - The level of autoantibodies (aAB) to main structural component of glutamate NMDA
      receptors--phencyclidin-binding protein--was measured in blood serum of 70
      patients during first 3, 6, 9, 12, 24 hours, and 3, 5 days after ischemic stroke
      development. 200 healthy individuals formed the control group. The elevation of
      titers of aAB to glutamate receptors was observed in all patients with severe or
      moderate disease from the very first hours of stroke. It was especially
      pronounced by 9-12 hours after stroke. The highest increase of aAB titers was
      found in severe cases. The tendency to normalization of aAB titers was observed
      by the end of the first twenty four hours. The degree of aAB elevation had the
      prognostic importance. The most favourable course of stroke with good restoration
      of damaged functions was predicted when stable normalization of the aAB level was
      observed by the third day of the disease development. Patients in stupor-coma
      condition did not show the phenomenon of aAB level's elevation during the first
      days of stroke, that reflected, probably, the development of immuno-deficient
      state. The decrease of aAB level down to subnormal values was extremely
      unfavourable prognostic sign proceeding patient's death as a rule.

PMID- 9012260
TI  - [Morphological changes in the vestibular analyzer in the dynamics of an
      experimental disorder of the cerebral circulation].
AB  - The alterations of microcirculatory structures and of neurons as a result of
      chronic cerebrovascular disturbances induced by ligation of the left common
      carotid artery were studied on 56 noninbred white male rats. The objects of
      investigation were central links of vestibular analyser such as anterior
      vestibular nucleus, posterior ventro-lateral part of hypothalamus, sensomotor
      brain cortex. It was established that one-sided ligation of common carotid artery
      resulted in alterations in vessels of microcirculatory bed, in neurons' bodies,
      in synapses. These disorders were similar to oxygen-deficient damages, described
      in literature which confirm the model's adequacy. These alterations appeared in
      different time and had various degree of expression in different structures. The
      latter observation may reflect different phylogenetic age of the structures
      studied. The reaction of the neuronal population as the functional system was
      observed as the process of alterations of the correlation of neurons with
      different functional activity. This process had periodic pattern.

PMID- 9012261
TI  - [Osmolality and ion concentration in the cerebrospinal fluid and blood serum in
      epilepsy and ischemic stroke].
AB  - A sharp (16.4%) increase of blood serum osmolality very close to the critical
      values was found in acute period of ischemic stroke, while sodiumemia exceeded
      the normal levels by 50 mmol/l and more. Meanwhile, the concentrations of Na ions
      in liquor of such patients was not significantly increased. The levels of Ca, K,
      Mg ions as well as the osmolality of blood serum and liquor were stable too. The
      alterations of these parameters were not significantly changed in epileptic
      patients out of fits. Both the analysis of the reasons of hyperosmia and
      hypersodiumemia development and the search for the methods of their prophylaxis
      and correction will be quite important in further investigations.

PMID- 9012262
TI  - [Aneurysms of the cerebral vessels].

PMID- 9012263
TI  - [Aicardi's syndrome: agenesis of the corpus callosum, infantile flexor spasms and
      macular dystrophy].

PMID- 9012264
TI  - [Electroneuromyostimulation in closed injuries to the peripheral nerves].

PMID- 9012265
TI  - [Possible risk factors of cerebral strokes].

PMID- 9012266
TI  - [The quantitative characteristics of the changes in the synaptic contacts in the
      hippocampus in Alzheimer's disease].

PMID- 9012267
TI  - [Migraine and cerebral stroke].

PMID- 9012268
TI  - Review of practice calls: Part two.

PMID- 9012269
TI  - [Treatment of asthma using aerosols].
AB  - The vast majority of clinicians in Europe now prescribe beta-2 agonists as first
      line therapy for patients with asthma. Inhaler devices may deliver rapidly acting
      (beta-2 sympathomimetics) and more slowly acting (anticholinergic) bronchodilator
      therapy as well as prophylactic medication (sodium cromoglycate and topical
      corticosteroids). The metered dose inhaler (MDI) is most often prescribed, but at
      least 50% of patients cannot use this device efficiently and 10-15% of those who
      can, develop an inefficient technique. The vast majority of those patients are
      able to use a single-dose dry power inhaler. Recent studies have shown that a
      multidose dry power system can be used by most patients and is preferred to the
      MDI by over two-thirds of patient. The large volume spacer systems have been
      shown to be as good as the MDI and nebulizer systems in the management of asthma,
      and they are easier to use than the MDI. Nebulisers are of value in chronic
      asthma in children who cannot use other delivery systems. The role of nebulisers
      for the domiciliary treatment of asthma in adults, however, remains
      controversial.

PMID- 9012270
TI  - Preschool deaf and hard of hearing students' interactions during ASL and English
      storytelling.

PMID- 9012271
TI  - Emerging infectious diseases: a challenge to all.
AB  - Emerging infections are defined as diseases of infectious origin with an
      incidence that has increased within the past two decades or threatens to increase
      in the near future. Some of these diseases are associated with newly discovered
      infectious agents; others are well-known conditions rapidly increasing in
      incidence. Five emerging infections are reviewed in this article: ehrlichiosis, a
      tick-borne infection caused by obligate intraleukocytic bacteria; infections
      caused by vancomycin-resistant enterococci, which have become a serious
      nosocomial problem; hantavirus pulmonary syndrome, a Sin Nombre virus infection
      associated with the adult respiratory distress syndrome and a high case fatality
      rate; infection with Escherichia coli strain O157:H7, which typically produces
      hemorrhagic colitis that may lead to the hemolyticuremic syndrome, and
      streptococcal toxic shock syndrome, a devastating illness often associated with
      necrotizing fasciitis and multiple organ failure.

PMID- 9012272
TI  - Management of clavicle fractures.
AB  - Fractures of the clavicle are among the most common fractures seen by family
      physicians. Common mechanisms of injury include a fall on an outstretched hand or
      direct trauma to the bone. Fractures of the middle third of the clavicle are the
      most common and usually heal without complication when managed with
      immobilization using a sling or figure-of-8 bandage. Fractures of the distal
      clavicle often are overlooked and may be difficult to distinguish from an
      acromioclavicular separation. These fractures are classified into three types.
      Types I and III fractures of the distal clavicle usually heal with symptomatic
      treatment. Type II fractures are displaced as a result of ligamentous disruption
      and usually require surgical repair. Fractures of the proximal third of the
      clavicle are uncommon. Nondisplaced proximal fractures are successfully treated
      with sling immobilization. Orthopedic referral is indicated for significant
      displacement or sternoclavicular dislocation. By following appropriate management
      guidelines, family physicians can successfully treat most clavicle fractures.

PMID- 9012273
TI  - An approach to diagnosing the acute sore throat.
AB  - Sore throat is a common presenting complaint. Although patients often are
      concerned that they may have group A beta-hemolytic streptococcal (GABHS)
      pharyngitis, most sore throats are not caused by this infection. A number of
      illnesses and conditions present as sore throat. After life-threatening
      conditions are excluded, efforts to identify and treat patients with GABHS
      pharyngitis are appropriate. Efforts should include a directed history and
      physical examination, looking for exudative pharyngitis with fever, adenopathy
      and lack of cough or other respiratory symptoms. These findings predict a
      positive GABHS culture rate of 50 percent or more. The rapid Streptococcus test
      has a high positive predictive value, but it has a lower sensitivity rate.
      Treatment strategies for patients with sore throat are based on epidemiologic
      factors, signs and symptoms, and results of laboratory tests.

PMID- 9012274
TI  - Diagnosis of spontaneous subarachnoid hemorrhage.
AB  - Spontaneous subarachnoid hemorrhage is usually the result of rupture of an
      intracranial saccular aneurysm or arteriovenous malformation. The hemorrhage is
      typically a cataclysmic event, heralded by severe headache, meningeal signs and
      neurologic dysfunction. About one-half of patients with aneurysmal rupture
      experience "sentinel headaches" days to weeks before a major hemorrhage.
      Diagnosis at this stage may permit treatment before the occurrence of a
      devastating neurologic event. Clinical suspicion of subarachnoid hemorrhage
      should be confirmed by computed tomographic evaluation. Initial treatment of
      patients with spontaneous subarachnoid hemorrhage includes resuscitation and/or
      stabilization, management of acute effects of the hemorrhage, and prompt referral
      for neurosurgical treatment.

PMID- 9012275
TI  - Immunization of adolescents.
AB  - This report concerning the immunization of adolescents (i.e., persons 11 to 21
      years of age, as defined by the American Medical Association [AMA] and the
      American Academy of Pediatrics [AAP]) is a supplement to previous publications
      (i.e., MMWR 1994;43[No. RR-1]1-38; the AAP 1994 Red Book: Report of the Committee
      on Infectious Diseases; Summary of Policy Recommendations for Periodic Health
      Examination, August 1996 from the American Academy of Family Physicians; and AMA
      Guidelines for Adolescent Preventive Services: Recommendations and Rationale).
      This report presents a new strategy to improve the delivery of vaccination
      services to adolescents and to integrate recommendations for vaccination with
      other preventive services provided to adolescents. This new strategy emphasizes
      vaccination of adolescents 11 to 12 years of age by establishing a routine visit
      to their health care providers. Specifically, the purposes of this visit are to
      (1) vaccinate adolescents who have not been previously vaccinated with varicella
      virus vaccine, hepatitis B vaccine, or the second dose of the measles, mumps and
      rubella vaccine; (2) provide a booster dose of tetanus and diphtheria toxoids;
      (3) administer other vaccines that may be recommended for certain adolescents,
      and (4) provide other recommended preventive services. The recommendations for
      vaccination of adolescents are based on new or current information for each
      vaccine.

PMID- 9012276
TI  - Preventing perinatal HIV transmission: zidovudine use during pregnancy.
AB  - Human immunodeficiency virus (HIV) infection and acquired immunodeficiency
      syndrome in women of childbearing age are increasing rapidly in the United
      States. Perinatal transmission can occur during pregnancy, delivery or breast
      feeding. Because 90 percent of pediatric HIV infections are caused by perinatal
      transmission, the U.S. Public Health Service has recommended that all pregnant
      women be offered HIV counseling and testing. Factors that influence perinatal
      transmission include high maternal viral load, low maternal CD4 count, prolonged
      rupture of the membranes, premature delivery and symptomatic maternal HIV
      infection. The results of a recent clinical trial demonstrate that if HIV
      infected women become pregnant, the use of zidovudine during the prenatal,
      intrapartum and neonatal periods can decrease by two-thirds the likelihood of HIV
      transmission to the baby. The U.S. Public Health Service, in conjunction with the
      American Academy of Family Physicians, has strongly recommended expanding the
      current noncoercive, voluntary HIV testing to include routine testing of all
      pregnant women.

PMID- 9012277
TI  - Eight key questions to ask when your patient with asthma doesn't get better.
AB  - Patients with asthma who are treated according to published guidelines usually
      have good outcomes. However, when these patients fail to improve despite our best
      efforts, a systematic review focusing on eight key questions can usually spot
      where the management plan went wrong. When we have to go back to the drawing
      board in the care of these patients, these are the important issues to consider:
      (1) Is it the environment? (2) Is it the workplace? (3) Is it noncompliance? (4)
      Is it lack of education? (5) Is it blunted patient perception? (6) Is it poor
      technique in administering medication? (7) Is it the wrong treatment? (8) Is it
      something other than asthma?

PMID- 9012278
TI  - Neurologic findings in vitamin E deficiency.
AB  - Vitamin E is one of the most important lipid-soluble antioxidant nutrients.
      Severe vitamin E deficiency can have a profound effect on the central nervous
      system. Cystic fibrosis, chronic cholestatic liver disease, abetalipoproteinemia,
      short bowel syndrome, isolated vitamin E deficiency syndrome and other
      malabsorption syndromes all may cause varying degrees of neurologic deficits due
      to related vitamin deficiencies. The classic abnormalities in vitamin E
      deficiency progress from hyporeflexia, ataxia, limitations in upward gaze and
      strabismus to long-tract defects, profound muscle weakness and visual field
      constriction. Patients with severe, prolonged deficiency may develop complete
      blindness, dementia and cardiac arrhythmias. Treatment must be tailored to the
      underlying cause of vitamin E deficiency and may include oral or parenteral
      vitamin supplementation. The more advanced the deficits, the more limited the
      response to therapy. Therefore, a good neurologic examination and periodic serum
      vitamin E levels are essential in patients at risk of vitamin E deficiency.

PMID- 9012279
TI  - Contemporary medical therapy for gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease is a chronic disorder that requires long-term
      therapy in most patients. The appropriate medical therapy should be
      individualized to the severity of symptoms, the degree of esophagitis and the
      presence of other acid-reflux complications. Lifestyle changes should form the
      basis of any therapeutic approach. In patients with mild to moderate disease,
      initial therapy with histamine H2-receptor antagonists in conventional dosages is
      suggested. Prokinetic agents are potentially useful in patients with impaired
      esophageal or gastric motor function, but their efficacy as single agents does
      not appear to surpass that of standard doses of H2 blockers. Sucralfate, a
      cytoprotective agent, is an additional therapeutic option. For patients with more
      severe disease, omeprazole and lansoprazole provide unequaled healing rates and
      accelerated symptom relief. In most patients, maintenance therapy is vital.
      Surgery is indicated in patients whose disease is refractory to medical therapy
      and in those who develop complications not amenable to medical therapy.

PMID- 9012280
TI  - Radionuclide imaging in the evaluation of heart disease.
AB  - Myocardial perfusion imaging with stress testing by exercise or pharmacologic
      methods and functional evaluation of the left ventricle are useful in many
      patients. Uses include determination of diagnosis and prognosis of patients with
      coronary artery disease, preoperative evaluation, management and risk
      stratification following cardiac events, evaluation of therapy and assessment of
      left ventricular status in many situations, including postmyocardial infarction
      and chemotherapy with cardiotoxic drugs. Many recent advances in imaging
      techniques, stress methods and radiopharmaceuticals make this a complex area of
      clinical diagnosis. It requires a coordinated effort of primary care, cardiology
      and nuclear medicine specialists to provide optimal patient care.

PMID- 9012281
TI  - Management of infantile colic.
AB  - Colic, or persistent unexplained crying in infants, is a disorder commonly
      encountered by the family physician. Although colic is not detrimental to an
      infant's health, it can place tremendous stress on the family. No effective cure
      for this disorder is known. Researchers have investigated a wide variety of
      therapies, including formula changes, pharmacotherapy and infant positioning
      maneuvers, but study results have been conflicting, controversial and
      inconclusive. At present, behavioral management, supportive counseling and
      parental reassurance are the mainstays of treatment. By formulating an effective
      individualized management plan, the family physician can help assist parents
      through the trying period of infantile colic.

PMID- 9012282
TI  - Major depression: assessing the role of new antidepressants.
AB  - Major depression is a common disorder. Historically, tricyclic antidepressants
      have been the standard pharmacologic agents in the treatment of this disorder.
      Unfortunately, the occurrence of significant side effects has limited the use of
      these drugs. In the past decade, however, antidepressants that are
      pharmacologically distinct from the tricyclics have been introduced. These newer
      drugs are tolerated better than the tricyclics and have been reported to have
      similar efficacy. Thus, because these newer agents provide effective, well
      tolerated treatment of mild to moderate depression, they are now generally
      preferred to the tricyclic antidepressants, despite their greater cost.

PMID- 9012283
TI  - Assuring up-to-date immunization of children aged 11 to 12 years.

PMID- 9012284
TI  - AAFP, AAP and ACIP release 1997 Childhood Immunization Schedule. AAFP Commission
      on Clinical Policies and Research and AAFP Liaison with the Advisory Committee on
      Immunization Practices.

PMID- 9012285
TI  - AAP issues guidelines for vision screening in infants, children and young adults.

PMID- 9012286
TI  - Emerging infections: not just a few needles in the haystack.

PMID- 9012287
TI  - Use of the Mogen clamp for neonatal circumcision.

PMID- 9012288
TI  - Use of the Mogen clamp for neonatal circumcision.

PMID- 9012289
TI  - Eccentric dosage regimen for isosorbide dinitrate.

PMID- 9012290
TI  - Eccentric dosage regimen for isosorbide dinitrate.

PMID- 9012291
TI  - Eccentric dosage regimen for isosorbide dinitrate.

PMID- 9012292
TI  - [Immunologic deficiency and pain].

PMID- 9012293
TI  - [Clinical medicine and research, old and new].

PMID- 9012294
TI  - [Pain syndromes in AIDS].
AB  - Pain is a major, but largely neglected problem in AIDS patients. The aim of this
      article is to review the etiology of pain manifestations in AIDS patients in
      different organ systems and to discuss appropriate treatment strategies. The most
      common pain symptoms in AIDS patients are headache, oral cavity pain, dysphagia
      and adynophagia, chest pain, abdominal pain and pain related to peripheral
      neuropathy. Symptomatic pain treatment should be started while diagnostic work-up
      is still in progress, so that the patient does not suffer. If etiological
      treatment is possible, specific treatment pain treatment tapered as tolerated. If
      etiological treatment is not possible, symptomatic pain treatment should be
      continued. In view of the multiple organs involved in the presentation of AIDS
      requiring multiple drugs, careful attention to side effects, contraindications
      and drug interactions is warranted, when administering pain medications. Fear of
      the complexity of these issues should, however, not prevent effective pain
      management for these patients, who suffer from a fatal disease. A
      multidisciplinary approach to pain in AIDS patients, similar to the approach in
      patients with cancer, is desirable.

PMID- 9012295
TI  - [The effect of total intravenous anesthesia with S-(+)-ketamine/propofol on
      hemodynamic, endocrine and metabolic stress reactions in comparison to
      alfentanil/propofol in laparotomy].
AB  - Total intravenous anaesthesia with ketamine-propofol offers distinct advantages
      over a TIVA with an opiate, including less cardiovascular and respiratory
      depression and an altered neuroendocrine and immunological stress response
      pattern. The effects of the more active stereoisomer S-(+)-ketamine in
      combination with propofol on the circulatory, endocrine and metabolic responses
      to abdominal surgery were compared with those of alfentanil-propofol. Twenty-four
      patients scheduled for elective hysterectomy participated in this study which had
      the approval of our institution's ethics committee. Anaesthesia was induced with
      2 mg/kg S-(+)-ketamine or 0.05 mg/kg alfentanil, followed by 1 mg/kg propofol.
      Tracheal intubation was facilitated with 0.06 mg/kg vecuronium. Anaesthesia was
      maintained with 1 mg/kg per h S-(+)-ketamine or 0.0125 mg/kg per h alfentanil and
      propofol at an initial rate of 15 mg/kg per h which was reduced to 5 mg/kg per h
      after 30 min. Blood samples for catecholamines, cortisol and metabolites were
      drawn at predetermined times from before induction to 6 h postoperatively.
      Adrenaline and noradrenaline concentrations decreased preoperatively in the
      ketamine group (K) from 55 to 29 pg/ml and 166 to 39 pg/ml, respectively, and
      then increased to postoperative maxima of 193 or 315 pg/ml. A similar pre and
      postoperative course was seen in the alfentanil group (A) with slightly lower (P
      < 0.05) intraoperative concentrations in A. Cortisol concentrations increased in
      K from 12 micrograms/dl to 34 micrograms/dl intraoperatively and further to a
      maximum of 42 micrograms/dl postoperatively. The intraoperative increase was
      attenuated in A and the difference between the groups was significant (P <
      0.0001). The initial ketamine bolus and tracheal intubation caused a marked,
      transient increase of mean arterial blood pressure from the baseline value of 105
      mmHg to 120 mmHg with a subsequent decrease to 88 mmHg prior to skin incision and
      a gradual return to baseline during surgery. TIVA with ketamine-propofol had
      little effect on the perioperative courses of the endocrine parameters, which
      behaved as they do under anesthesia with isoflurane-nitrous oxide. Plasma
      catecholamine concentrations were not elevated in the period between induction of
      anaesthesia and skin incision.

PMID- 9012296
TI  - [Cardiovascular effects after bolus administration of cisatracurium. A comparison
      with vecuronium].
AB  - Cisatracurium-one of the ten stereoisomers of atracurium-is an intermediate long
      acting non-depolarizing neuromuscular blocking agent. Cardiovascular reactions
      have been described after administration of cisatracurium or vecuronium in
      surgical patients. METHODS: After approval by our institutional review board, 62
      patients (ASA I-II) were randomly assigned to three groups to either receive
      3xED95 or 5xED95 of cisatracurium or 3xED90 of vecuronium prior to intubation as
      a bolus. After oral premedication with 2 mg lormetazepam anaesthesia was induced
      with thiopental (4-12 mg/kg) and maintained with O2/N2O and isoflurane (1.5%-2%).
      Six minutes after administration of thiopental, patients received the muscle
      relaxant. Six minutes later 0.1-0.2 mg fentanyl was given and the trachea was
      intubated. Heart rate (HR) and blood pressure (BP) were monitored every minute.
      Changes of heart rate or blood pressure > 20% compared to baseline were defined
      as clinically significant. RESULTS: After application of the study drug, median
      values of blood pressure and heart rate were stable. For each muscle relaxant,
      there were several patients who had statistically significant cardiovascular
      changes. After 3xED95 cisatracurium, 3 of 21 patients exhibited haemodynamic
      changes > 20% (2 exhibited hypotension and 1 tachycardia), while in the high-dose
      cisatracurium group 2 of 21 patients demonstrated a tachycardia that was
      predetermined to be statistically but not clinically significant. In the
      vecuronium group, 2 of 20 patients sustained statistically significant
      hypotension and 1 patient had statistically significant tachycardia. The
      frequency of all individual cardiovascular changes after the application of the
      muscle relaxant was not dose-dependent. CONCLUSION: After the administration of
      cisatracurium in two different doses (3xED95 and 5xED95) or vecuronium (3xED90)
      only minor cardiovascular changes were observed. Both drugs proved to be safe for
      use during induction of anaesthesia in patients ASA I-II. With regard to its
      cardiovascular effects, cisatracurium shares with vecuronium the requirements of
      an ideal muscle relaxant.

PMID- 9012297
TI  - [Measurement of human cerebrovascular circulation. Comparison of Kety-Schmidt
      technique with the intravenous 133-xenon clearance technique].
AB  - In this study cerebral blood flow (CBF) was simultaneously measured with the Kety
      Schmidt method and the intravenous 133Xe clearance technique. CBF, cerebral
      metabolic rate of oxygen (CMRO2), and CO2 reactivity of CBF were compared under
      fentanyl-midazolam anaesthesia and varying paCO2 levels. METHODS: Thirteen male
      patients were studied before they underwent coronary artery bypass surgery. For
      measurement of CBF with the Kety-Schmidt inert gas saturation technique, argon
      was used as indicator instead of nitrous oxide, because argon is less soluble in
      water and lipid such that arterial and hence organ saturation is attained
      earlier. Wash-in periods of 10 min were used for all measurements. For
      measurement of CBF with the intravenous xenon method 10 scintillation detectors
      placed lateral to the skull and an air detector for calculation of tracer
      recirculation were used. 10-15 mCi of 133Xe dissolved in physiological saline was
      injected via a peripheral i.v. cannula. For comparison with the Kety-Schmidt
      technique CBF15-values representing the flow of the grey and white matter were
      chosen. CBF was measured simultaneously with both methods under normocapnic
      (paCO2 43 +/- 3 mmHg), hypocapnic (paCO2 31 +/- 3 mmHg), and under hypercapnic
      (paCO2 54 +/- 4 mmHg) conditions. RESULTS: All CBF15 values obtained with the
      intravenous xenon method were significantly lower than the corresponding CBF
      values measured with the Kety-Schmidt technique: by 36% under normocapnic, 23%
      under hypocapnic, and 39% under hypercapnic conditions, respectively. Hence,
      CMRO2 values calculated from CBF values obtained with the xenon method were
      reduced to about the same degree as those derived from CBF values measured with
      the Kety-Schmidt technique. There was no significant correlation between the CBF
      values of either method (y = 1.82x-8.58,r = 0.76 P = 0.357). Non-linear curve
      fitting procedures yielded exponential CBF-paCO2 relationships for both methods,
      although the relative carbon dioxide reactivity was higher with the Kety-Schmidt
      technique than with the xenon method (y = 8.14 e0.039x vs y = 10,75 e0.023x).
      CONCLUSIONS: Most probably due to contamination with radioactivity from slowly
      perfused extracerebral tissues the intravenous 133Xe-clearance technique
      underestimates CBF, CMRO2, and cerebrovascular CO2 reactivity, at least when
      CBF15 values are used as flow parameters.

PMID- 9012298
TI  - [The effect of nitroglycerin on cerebrovascular circulation, cerebrovascular CO2
      reactivity and blood flow rate in basal cerebral arteries].
AB  - The cerebral haemodynamic effects of vasodilators are of clinical interest
      because a decrease in mean arterial pressure (MAP) might alter global cerebral
      blood flow (CBF). Luxury perfusion of the brain, contrast, might be unfavourable
      in patients with reduced intracranial compliance. Despite the widespread use of
      nitroglycerine (NTG), little is known about the cerebral haemodynamic consequence
      of NTG infusions in humans. This prospective, controlled study was designed: (1)
      to investigate the effects of NTG on CBF and cerebrovascular CO2 reactivity and
      (2) to compare reference measurements of global CBF with transcranial Doppler
      monitoring (TCD) of middle cerebral artery flow velocity (VMCA). METHODS: With
      ethical committee approval and informed patient consent, we investigated ten
      patients undergoing coronary artery bypass surgery. Measurements were performed
      under fentanyl/midazolam anaesthesia prior to the start of the operation. First,
      during a baseline period, ventilation was changed in a random sequence to achieve
      two different levels of arterial PCO2 (30 and 50 mmHg, respectively).
      Consequently, measurements were repeated during i.v. infusion of
      1.5.micrograms.kg-1.min-1 NTG at identifical PCO2 levels. Measurements of CBF
      were performed by the Kety-Schmidt technique with argon as an indicator.
      Simultaneously, VMCA was recorded by use of a 2-Mhz transcranial Doppler system.
      Cerebral perfusion pressure (CPP) was calculated from the difference between MAP
      and jugular bulb pressure. Statistical analysis was performed by two-way analysis
      of variance using a repeated-measures design to assess the effects of NTG
      application and respiratory changes, respectively. RESULTS: During NTG infusion,
      CPP decreased slightly by 15-17%. Because of a reduction in cerebrovascular
      resistance, CBF increased at both levels of PaCO2 by 96 and 69%, respectively.
      However, VMCA decreased concomitantly. Cerebrovascular CO2 reactivity did not
      change. CONCLUSIONS: This study demonstrates that during fentanyl/midazolam
      anaesthesia NTG may cause a major increase in CBF as long as CPP does not
      decrease considerably. Our results further suggest that NTG causes vasodilation
      of basal cerebral arteries, inducing a discrepancy between relative changes in
      CBF and VMCA. Consequently, TCD measurements during infusion of NTG should not be
      directly compared with preceding measurements of MCA flow velocity.

PMID- 9012299
TI  - [Cardiac output determination with transpulmonary thermodilution. An alternative
      to pulmonary catheterization?].
AB  - Cardiac output measurements are often helpful in the management of critically ill
      patients and high risk-patients. In this study an alternative technique for
      measurement of cardiac output by the transpulmonary indicator dilution technique
      (TPID) was evaluated in comparison to conventional thermodilution using a
      pulmonary artery catheter. With TPID, a thermistor-tipped catheter (the smallest
      available is 1.3 F) is placed in the aorta via a femoral artery introducer. Thus,
      TPID can also be used in very small children in whom placement of a pulmonary
      artery catheter may be difficult or even impossible. In principle, TPID is less
      invasive since the possible complications of the pulmonary catheters are avoided.
      We investigated the accuracy and reproducibility of transpulmonary thermodilution
      in patients over a broad range in age and body surface. METHODS: Following
      approval by the ethics committee and written consent, the data were obtained from
      21 patients without a circulatory shunt undergoing diagnostic heart
      catheterization. The patients were between 0.5 and 25.2 years old, their body
      surface between 0.35 and 1.89 m2. Measurements were performed in duplicate with
      bolus injections of ice-cold normal saline (0.15 ml/kg), randomly spread over the
      respiratory cycle. In total 48 thermodilution curves were measured simultaneously
      in the pulmonary artery and in the aorta. Thermodilution curves were
      monoexponentially extrapolated for elimination of recirculation and cardiac
      output was calculated with a standard Stewart Hamilton procedure. RESULTS: The
      amplitude of the typical arterial thermodilution curve shows a smaller and more
      delayed course than the pulmonary artery thermodilution curve. There was a very
      good correlation between the values found by pulmonary and TPID cardiac output
      measurements (R = 0.968). There was a slightly smaller cardiac output value
      measured by the TPID (Bias = -4.7 +/- 1.5% sem) The reproducibility of duplicate
      measurements with the two methods were nearly the same, the standard deviation of
      the difference was 10.9% for the pulmonary thermodilution method and 11.7% for
      TPID. DISCUSSION. TPID gives an alternative technique for measurement of cardiac
      output. We showed over a broad range in age and body surface a very good
      correlation with thermodilution measurements in the pulmonary artery. The
      slightly smaller values for TPID are explained by early recirculation, for
      clinical purposes the difference is negligible. However, the reproducibility of a
      method is clinically very important. Both methods showed in duplicate
      measurements basically the same reproducibility. The disadvantage of TPID in
      being more sensitive to baseline alteration is counterbalanced by less
      respiratory variability in comparison to the conventional thermodilution
      technique. However, by increasing the amount of injected indicator (i.e., 0.2
      ml/kg approximately equal to 15 ml in an adult) it is possible to reduce the
      effect of baseline alteration. By using fiberoptic catheters it is even possible
      to use TPID as double-indicator dilution technique to measure intrathoracic blood
      volume (ITBV) and extravascular lung water (EVLW). We conclude that in many
      patients TPID might be an attractive, less invasive and reliable alternative to
      conventional cardiac output measurement by pulmonary artery catheter.

PMID- 9012300
TI  - [Variation in inspiratory gas flow in pressure support ventilation. The effect on
      respiratory mechanics and respiratory work].
AB  - During pressure support ventilation (PSV), the timing of the breathing cycle is
      mainly controlled by the patient. Therefore, the delivered flow pattern during
      PSV might be better synchronised with the patient's demands than during volume
      assisted ventilation. In several modern ventilators, inspiration is terminated
      when the inspiratory flow decreases to 25% of the initial peak value. However,
      this timing algorithm might cause premature inspiration termination if the
      initial peak flow is high. This could result not only in an increased risk of
      dyssynchronization between the patient and the ventilator, but also in reduced
      ventilatory support. On the other hand, a decreased peak flow might
      inappropriately increase the patient's inspiratory effort. The aim of our study
      was to evaluate the influence of the variation of the initial peak-flow rate
      during PSV on respiratory pattern and mechanical work of breathing. PATIENTS: Six
      patients with chronic obstructive pulmonary disease (COPD) and six patients with
      no or minor nonobstructive lung pathology (control) were studied during PSV with
      different inspiratory flow rates by variations of the pressurisation time (Evita
      I, Dragerwerke, Lubeck, Germany). During the study period all patients were in
      stable circulatory conditions and in the weaning phase. METHOD: Patients were
      studied in a 45 degrees semirecumbent position. Using the medium pressurization
      time (l s) during PSV the inspiratory pressure was individually adjusted to
      obtain a tidal volume of about 8 ml/kg body weight. Thereafter, measurements were
      performed during five pressurization times (< 0.1, 0.5, 1, 1.5, 2 s defined as T
      0.1, T 0.5, T 1, T 1.5 and T 2) in random order, while maintaining the pressure
      support setting at the ventilator. Between each measurement steady-state was
      attained. Positive end-exspiratory pressure (PEEP) and FIO2 were maintained at
      prestudy levels and remained constant during the study period. Informed consent
      was obtained from each patient or his next of kin. The study protocol was
      approved by the ethics committee of our medical faculty. Gas flow was measured at
      the proximal end of the endotracheal tube with a pneumotachometer (Fleisch no. 2,
      Fleisch, Lausanne, Switzerland) and a differential pressure transducer. Tracheal
      pressure (Paw) was determined in the same position with a second differential
      pressure transducer (Dr. Fenyves & Gut, Basel, Switzerland). Esophageal pressure
      (Pes) was obtained by a nasogastric balloon-catheter (Mallinckrodt, Argyle, NY,
      USA) connected to a further differential pressure transducer of the same type as
      described above. The balloon was positioned 2-3 cm above the dome of the
      diaphragm. The correct balloon position was verified by an occlusion test as
      described elsewhere. The data were sampled after A/D conversion with a frequency
      of 20 Hz and processed on an IBM-compatible PC. Software for data collection and
      processing was self-programmed using a commercially available software program
      (Asyst 4.0, Asyst Software Technologies, Rochester, NY, USA). Patient's
      inspiratory work of breathing Wpi (mJ/l) was calculated from Pes/ volume plots
      according to the modified Campbell's diagram. Dynamic intrinsic PEEP (PEEPidyn)
      was obtained from esophageal pressure tracings relative to airway pressure as the
      deflection in Pes before the initiation of inspiratory flow Patient's additive
      work of breathing (Wadd) against ventilator system resistance was calculated
      directly from Paw/V tracings when Paw was lower than the pressure on the
      compliance curve. Two-way analysis of variance (ANOVA) was used for statistical
      analysis, followed by post hoc testing of the least significant difference
      between means for multiple comparisons. Probability values less than 0.05 were
      considered as significant. RESULTS: COPD patients had significantly higher
      pressure support than control patients. With decreasing inspiratory flow, Wpi
      increased significantly in COPD patients.(ABSTRACT TRUNCATED)

PMID- 9012301
TI  - [Infrared temperature measurement in the ear canal with the DIATEK 9000 Instatemp
      and the DIATEK 9000 Thermoguide. Comparison with methods of temperature
      measurement in other body parts].
AB  - Temperature of the tympanic membrane is recommended as a "gold standard" of core
      temperature recording. However, use of temperature probes in the auditory canal
      may lead to damage of tympanic membrane. Temperature measurement in the auditory
      canal with infrared thermometry does not pose this risk. Furthermore it is easy
      to perform and not very time-consuming. For this reason infrared thermometry of
      the auditory canal is becoming increasingly popular in clinical practice. We
      evaluated two infrared thermometers-the Diatek 9000 Thermoguide and the Diatek
      9000 Instatemp-regarding factors influencing agreement with conventional tympanic
      temperature measurement and other core-temperature recording sites. In addition,
      we systematically evaluated user dependent factors that influence the agreement
      with the tympanic temperature. MATERIALS AND METHODS: In 20 volunteers we
      evaluated the influence of three factors: duration of the devices in the auditory
      canal before taking temperature (0 or 5 s), interval between two following
      recordings (30, 60, 90, 120, 180 s) and positioning of the grip relative to the
      auditory-canal axis (0, 60, 180 and 270 degrees). Agreement with tympanic contact
      probes (Mon-a-therm tympanic) in the contralateral ear was investigated in 100
      postoperative patients. Comparative readings with rectal (YSI series 400) and
      esophageal (Mon-a-therm esophageal stethoscope with temperature sensor) probes
      were done in 100 patients in the ICU. The method of Bland and Altman was taken
      for comparison. RESULTS: Shortening of the interval between two consecutive
      readings led to increasing differences between the two measurements with the
      second reading decreasing. A similar effect was seen when positioning the
      infrared thermometers in the auditory canal before taking temperatures: after 5 s
      the recorded temperatures were significantly lower than temperature recordings
      taken immediately. Rotation of the devices out of the telephone handle position
      led to increasing lack of agreement between infrared thermometry and contact
      probes. Mean differences between infrared thermometry (Instatemp and Thermoguide,
      CAL-Mode) and tympanic probes were -0.41 +/- 0.67 degree C (2 SD) and -0.43 +/-
      0.70 degree C, respectively. Mean differences between the Thermoquide (Rectal
      Mode) and rectal probe were -0.19 +/- 0.72 degree C, and between the Thermoguide
      (Core Mode) and esophageal probe -0.13 +/- 0.74 degree C. DISCUSSION: Although
      easy to use, infrared thermometry requires careful handling. To obtain optimal
      recordings, the time between two consecutive readings should not be less than two
      min. Recordings should be taken immediately after positioning the devices in the
      auditory canal. Best results are obtained in the 60 degrees position with the
      grip of the devices following the ramus mandibulae (telephone handle position).
      The lower readings of infrared thermometry compared with tympanic contact probes
      indicate that the readings obtained represent the temperature of the auditory
      canal rather than of the tympanic membrane itself. To compensate for
      underestimation of core temperature by infrared thermometry, the results obtained
      are corrected and transferred into core-equivalent temperatures. This data
      correction reduces mean differences between infrared recordings and traditional
      core-temperature monitoring, but leaves limits of agreement between the two
      methods uninfluenced.

PMID- 9012302
TI  - [The comparative effectiveness of different infusion and blood warming methods].
AB  - Heat loses during surgery occur mainly to the environment and due to infusions
      and irrigations. Infusions given at room temperature account for a great deal of
      the total heat deficit during major operations, e.g., the infusion of 53 ml/kg 20
      degrees C fluid leads to a loss of 1 degree C in mean body temperature. Hence,
      heating i.v. fluids will add to the effect of other measures aimed at reducing
      heat loss to the environment. We investigated the efficacy of different warming
      methods for i.v. fluids in an experimental model by measuring the temperature at
      the end of the delivery line. METHODS: The following in-line warmers were
      studied: Hotline HL-90 and System H-250/heat exchanger D-50 (Level 1
      Technologies, Marshfield, USA), Astotherm IFT 260 (Stihler Elektronic GmbH,
      Stuttgart, Germany), RSLB 30 H Gamida (Productions Hospitalieres Francaises,
      Eaubonne, France), Bair Hugger 241/Modell 500 Prototype (Augustine Medical, Eden
      Prairie, USA). They were compared with pre-warming infusions (39 degrees C) only
      using the Clinitherm S (Labor Technik Barkey GmbH, Bielefeld, Germany) and pre
      warming with "active insulation" of the delivery line using the
      Autotherm/Autoline system (Labor Technik Barkey GmbH, Bielefeld, Germany). We
      investigated the influence of four variables on the efficacy of warming: (1) flow
      rate (50-15,000 ml/h); (2) ambient temperature (20 degrees C and 25 degrees C);
      (3) infusion bag temperature (6 degrees C, 20 degrees C, and 39 degrees C); and
      (4) length of infusion system downstream from the heat exchanger. Fluid
      temperatures were measured using thermistors of 1 mm diameter (Modell YSI 520,
      Yellow Springs Instruments Co., Yellow Springs, USA) incorporated into 3-way
      stopcocks. Temperatures were recorded using Hellige temperature monitors (Hellige
      GmbH, Freiburg im Breisgau, Germany) and the signals were collected at 10 Hz
      through an AD converter and averaged over 1 min. Flows were calculated by timed
      collection into calibrated cylinders; 10 to 12 different flow rates were taken to
      define one temperature/ flow plot. Effective warming was defined as a temperature
      > 33 degrees C at the end of the infusion line. RESULTS: At high flow rates (>
      2,500 ml/h) using 20 degrees C fluids at 20 degrees C ambient temperature, the H
      250/D-50 system gave the highest temperatures throughout the range and showed
      effective warming from 1,300 ml/h on over the entire range tested (35 degrees C
      at 17,000 ml/h) compared to the RSLB 30 H Gamida system (3,000-18,000 ml/h) (Fig.
      2). This difference in performance was almost abolished with fluids at 6 degrees
      C (Fig. 4). Similar efficacy could be reached by using prewarmed infusions that
      gave effective warming at > 2,000 ml/h and reached 39 degrees C at 13,000 ml/h.
      Prewarmed infusions could be used effectively down to > 80 ml/h applying "active
      insulation" (Autotherm/Autoline) to the whole infusion system. The Hotline HL-90
      (50-4, 700 ml/h) appeared to be the most effective in-line warmer in the low (<
      250 ml/h) and middle (250-2,500 ml/h) flow range, followed by the Astotherm IFT
      260 (400-4,000 ml/h), but only if used with a length of 40 cm down-stream from
      the heat exchanger (Fig. 1). Increasing this distance to 145 cm markedly reduced
      its efficacy below the range of 2,000 ml/min (1,200- 3,000 ml/h) (Fig. 5). The
      Bair Hugger 241 Prototype showed a narrow effective range (700-1,300 ml/h) that
      could be extended beyond 1,300 ml/h by the use of prewarmed infusions (Figs. 1
      and 3). The performance for 6 degrees C solutions and ambient temperatures of 25
      degrees C are given in Fig. 4 and Table 1. CONCLUSIONS: The importance of
      infusion warming increases with the amount of fluid given.(ABSTRACT TRUNCATED)

PMID- 9012303
TI  - [The effect of convection warming during abdominal surgery on the early
      postoperative heat balance].
AB  - Hypothermia (core temperature < 36 degrees C) is common after longer-lasting
      surgical procedures. Heat loss mainly occurs during anaesthesia and surgery and
      leads to increased risk, especially in the early recovery period of elderly
      patients. In the present study we investigated the effects of intraoperative
      forced-air warming, administered via an upper-body blanket ("Warm Touch",
      Mallinckrodt, USA), with the specific aims of: (1) drawing up heat balances; and
      (2) analysing postoperative thermoregulation, oxygen consumption (VO2) and
      cardiovascular reactions of mechanically ventilated patients. The general aim of
      our study was to compare intraoperative forced-air-warming and conventional
      patient-insulation with cotton blankets. METHODS: Twenty four ASA II and III
      patients scheduled for elective colon surgery were randomly assigned to a control
      group (n = 12, no warming therapy, upper body covered with a cotton hospital
      blanket) or a convective warming group (n = 12). Anaesthesia was administered
      with etomidate (0.2 mg/kg), fentanyl (approximately 10 micrograms/kg) and
      vecuronium bromide (0.1 mg/kg). During surgery the lungs were mechanically
      ventilated with 70% nitrous oxide in oxygen and enflurane (end-tidal
      concentration max. 0.7%) using a semiclosed circuit with a fresh gas flow of 3
      l/min. A hygrophobe heat and moisture exchanger ("Sterivent," Darex Corp., Italy)
      was used. At the end of surgery patients were transferred to the ICU, covered
      with a hospital cotton-quilt and normo-ventilated using a Bennett 7200 a.
      Patients were sedated/kept free of pain by administering titrated doses of
      midazolam and/or piritramide. Postoperative oxygen consumption (VO2) was recorded
      continuously with a Deltatrac Metabolic Monitor (Datex Corp., Finland). Pre-,
      intra- and postoperative measurements included heart rate, invasive blood
      pressure, core-temperature (before and after operation: urinary bladder
      temperature, during surgery: oesophageal temperature) and mean-skin-temperature
      (according to Ramanathan) up to 180 min from the end of surgery. Shivering,
      pharmacological interventions (e.g. pethidine) and time of extubation were noted.
      Data are presented as median, minima and maxima. The results were analysed using
      the Mann-Whitney U test or Chi-Square test (shivering). Statistical significance
      was assumed when P < 0.05. RESULTS: Both groups were comparable for gender, body
      weight, height, age, duration of their operations and amount of intraoperative
      fluids, narcotics and muscle relaxants. Room temperatures in the control group
      were significantly higher than in the forced air group (24 vs 22 degrees C).
      Initial setting of the forced-air blower was "high" (42-46 degrees high air
      flow). When the oesophageal-temperature reached 36.5 degrees C, the blower
      temperature was reduced to 36-40 degrees C. Reduction was necessary approximately
      60 min from start in the operation. At the end of surgery/administration to the
      ICU core-temperatures of both groups differed significantly (35.2/ 35.4 degrees C
      vs 36.3/36.2 degrees C). Mean-skin temperatures were higher, too, but no
      statistical analysis was carried out for the intraoperative period, because warm
      air influenced skin thermometers located on the upper body. At admission to the
      ICU patients in the control group had a heat loss of 4.4 kJ/kg; those in the
      convective warming group had a heat-gain of 0.8 kJ/kg. Further measurements of
      postoperative core temperatures did not differ significantly, but the skin
      temperatures of patients who received forced-air warming in the theatre remained
      higher (P < 0.05) until 120 min from the end of surgery. Shivering was more
      frequent and lasted longer in the control group (8 patients, 20 min vs 4
      patients, 9 min; P < 0.05). Patients in the control group needed more drugs to
      stop increased cardiovascular reactions (hypertension, tachycardia) or
      shivering.(ABSTRACT TRUNCATED)

PMID- 9012305
TI  - [The effect of the laryngeal mask airway on the postoperative incidence of
      vomiting and sore throat in children].
AB  - 100 ASA I and II children, aged 4 to 14 years, and scheduled for strabismus
      surgery, were randomly assigned to one of the following groups: group 1 (n = 50):
      endotracheal tube, group 2 (n = 50): laryngeal mask airway. Apart from airway
      management, the anaesthesiological procedures were identical in both groups:
      induction with 2-3 mg/kg propofol, 0.02 mg/kg alfentanil, 0.05 mg/kg vecuronium,
      and 0.01 mg/kg atropine. After endotracheal intubation or insertion of the
      laryngeal mask, anaesthesia was continued with 6-15 mg/kg.h propofol and 10-30
      micrograms/kg.h alfentanil. All patients were ventilated with N2O/O2 (2:1). No
      antiemetics were given, gastric contents were not aspirated. Postoperative nausea
      and vomiting (PONV) were recorded by 24 h, the incidence of sore throats was
      recorded 8, 12, and 24 h post-operatively. RESULTS: The incidence of PONV was
      higher in group 1 (vomiting 48% vs 32%), nausea 28% vs 16% n.s.). Group 1
      children had a higher incidence of sore throats (20% vs. 12%, n.s.), of a "lump
      in the throat" (10% vs 4%, n.s.), hoarseness (24% vs 0%, p < 0.001) and
      dysarthria (10% vs 4%, n.s.). CONCLUSIONS: In children undergoing strabismus
      surgery, the laryngeal mask airway was superior to the endotracheal tube in terms
      of PONV and was associated with fewer local complications such as sore throat.

PMID- 9012304
TI  - [Propofol and etomidate-Lipuro for induction of general anesthesia. Hemodynamics,
      vascular compatibility, subjective findings and postoperative nausea].
AB  - Etomidate has become an important induction agent in high-risk patients because
      of its cardiovascular stability. Its unwanted side-effects such as pain on
      injection and thrombophlebitis could be significantly reduced by a new (medium
      chain triglyceride and soya bean) emulsion formulation. Propofol is solved in a
      mixture of long chain triglyceride and soya bean emulsion. In this double-blind,
      randomized study we compared the haemodynamic effects, the patients' sensations,
      signs of thrombophlebitis and postoperative nausea and vomiting (PONV) following
      injection of both drugs. METHODS: Following premedication with 2 mg Lormetazepam
      p.o. in 50 patients per group, anaesthesia was induced with either 0.51 mg
      etomidate in lipid emulsion or 3.04 mg propofol per kg bw. No opioid or
      benzdiazepine was given i.v. before induction. After injection of the tested
      drug, the cannula was removed. Changes in blood pressure and heart rate were
      recorded as well as signs of discomfort during and after injection (pain,
      burning, tension, cold). Venous sequelae were assessed for 5 days after injection
      to register signs of thrombophlebitis. RESULTS: Demographic data showed no
      difference between the two groups. After propofol more often a fall in blood
      pressure was seen. Pain (25 vs 1 pt), burning 19 vs 1), tension 15 vs 3), cold
      (35 vs 17) after injection was registered significantly more often in the
      propofol group, whereas myocloni predominated in the etomidate group (13 vs 6) P
      < 0.05, chi-squared-test). No difference was seen in PONV in either groups.
      CONCLUSION: Etomidate formulated in a medium chain lipid emulsion causes
      significant less discomfort for the patients than propofol, which is solved in a
      long chain formulation. Myocloni, however, occur significantly more frequently
      after etomidate than after propofol.

PMID- 9012306
TI  - [Intraoperative acute aortic obstructive embolism].
AB  - We report a case of acute embolic obstruction of the aorta in a 36-year-old
      patient undergoing coronary artery bypass surgery. After declamping of the aorta
      at the end of extracorporeal circulation, blood pressure measured in the femoral
      artery dropped to 10-20 mmHg. Neither clinical signs of arterial hypotension nor
      a dysfunction of the arterial line could be observed. Cannulation of the left
      radial artery revealed a normal systemic blood pressure. After the end of
      surgery, pale and pulseless lower extremities were observed, suggesting arterial
      obstruction. A 6 X 3 cm embolus occluding the aortic bifurcation could be
      extracted with a Fogarty catheter; its origin was presumably an aneurysmatic area
      of the left ventricle. Surgical manipulation had mobilised the mural thrombus,
      which caused Leriche's syndrome after aortic declamping and defibrillation of the
      heart. CONCLUSION: In case of sudden alterations of lower extremity perfusion,
      anaesthetists and surgeons should consider the rare complication of acute embolic
      obstruction of the aorta originating from intracardiac thrombotic material.
      Routine monitoring with transoesophageal echocardiography should thus be
      considered in patients at risk for intracardiac thrombus formation.

PMID- 9012307
TI  - [Severe, accidental hypothermia: active rewarming with a simple extracorporeal
      veno-venous warming-circuit].
AB  - We report the case of a 35-year-old male who was admitted to the intensive care
      unit because of somnolence due to accidental hypothermia. Initial examination
      showed a Glasgow coma score of 10 and a rectal temperature of 27.4 degrees C.
      Because of stable circulatory conditions, there was no mandatory indication for
      rewarming by means of cardiopulmonary bypass. We rewarmed the patient with an
      extracorporeal veno-venous haemofiltration device combined with a countercurrent
      fluid warmer. An average increase in body temperature of 1.34 degrees Ch-1 could
      be obtained. We conclude that the described technique represents an effective and
      well-controllable method for treatment of hypothermia in patients with stable
      haemodynamic conditions. Because of the availability of the required equipment,
      this method can also be practised in hospitals without cardiac surgical
      departments and cardiopulmonary bypass facilities.

PMID- 9012308
TI  - [Limitations of inhaled vasodilators].
AB  - Treatment of pulmonary hypertension is an important issue in intensive care. One
      therapeutic regimen involves the intravenous administration of prostacyclin
      (PGI2). This, however, is accompanied by diminished hypoxic pulmonary
      vasoconstriction, reduced arterial oxygenation, and systemic vasodilation. Thus,
      its clinical usefulness is limited. However, the inhalation of vasodilators such
      as nitric oxide (NO) or nebulized PGI2 causes a selective pulmonary vasodilation
      in ventilated alveoli and improved gas exchange, without any systemic
      vasodilation. It has therefore gained importance for the treatment of pulmonary
      failure associated with high shunt fractions. However, the inhalation of
      vasodilators may have adverse effects: in the case of NO, toxic side effects are
      predominant (MetHb, NOx), whereas in the case of PGI2, technical problems in
      terms of dosing and administration safety are of major interest. Furthermore,
      some patients do not respond to the treatment. In some individuals a reduction in
      pulmonary hypertension can be seen, while others lack even pulmonary
      vasodilation. The exact pathophysiological mechanisms remain to be investigated.

PMID- 9012309
TI  - [Traffic accidents as a couse for emergency hospitalization].

PMID- 9012310
TI  - [Infections from intravascular catheterization].

PMID- 9012311
TI  - Proceedings of the XII World Congress of the International Union of Phlebology-
      parallel session entitled medical and socioeconomic impact of venolymphatic
      disease: benefit of daflon 500 mg. London, 1995.

PMID- 9012314
TI  - Apolipoprotein E Genotyping in Alzheimer's Disease. Chicago, Illinois, October 21
      22, 1995. Proceedings.

PMID- 9012313
TI  - Microbial Pathogenesis and Immune Response II. Proceedings of a conference. New
      York, New York, October 25-28, 1995.

PMID- 9012315
TI  - NIA/AIzA Conference on apolipoprotein E genotyping in Alzheimer's disease.
      Bibliography.

PMID- 9012316
TI  - Role of agriculture in creating values for the country and improving the quality
      of life for the people of Malaysia towards de year 2020.

PMID- 9012317
TI  - Ethical questions on the relationship between health damage and environmental
      causes.

PMID- 9012318
TI  - Atmospheric particulate pollutants and environmental health.

PMID- 9012319
TI  - A cohort study on mortality and exposure to polychlorinated biphenyls.
AB  - In 1979, an outbreak of food poisoning ("Yu-Cheng") occurred in Central Taiwan,
      ROC, involving more than 2000 people. The event was caused by ingestion of rice
      oil contaminated with polychlorinated derivatives of biphenyls, dibenzofurans,
      and quaterphenyls. A retrospective cohort study on mortality was undertaken, and
      possible long-term health effects in the affected individuals were studied. The
      mortality experience of 1940 victims (929 males, 1011 females) between 1980 and
      1991 was compared with the expected numbers, which were calculated from national
      and local mortality rates. By the end of 1991, 102 deaths were identified, thus
      producing a standardized mortality ratio (SMR) of overall mortality of 0.99 for
      males and 1.34 for females. Total cancer mortality was lower than in each
      comparison group. Mortality from liver diseases was elevated significantly (SMR =
      3.22), especially during the first 3 y after the food-poisoning event (SMR =
      10.76). Increased clinical severity of polychlorinated biphenyl intoxication was
      associated with increased mortality from all causes and from liver diseases. In
      summary, there was a positive association between mortality and intoxication
      dose, and severe polychlorinated biphenyl poisoning acutely affected mainly the
      liver. A continued follow-up of this cohort would be valuable in the study of
      long-term health effects of polychlorinated biphenyl poisoning.

PMID- 9012320
TI  - Serum immunoglobulin E and hyaluronate levels in children living along major
      roads.
AB  - To assess the effects of automobile exhaust on human health, we determined serum
      concentrations of total immunoglobulin E and hyaluronate in 185 schoolchildren
      who lived in a district that contained major roads. Serum immunoglobulin E levels
      were elevated in children who had asthma or wheezing, but levels did not differ
      with respect to distance of their homes from the major roads. Serum hyaluronate
      levels were higher in children who lived less than 50 m from the roadside,
      compared with children who resided a greater distance from roads. The difference,
      however, was significant only in a subgroup of children in whom immunoglobulin E
      levels exceeded 250 IU/ml. Our results suggest that serum hyaluronate levels in
      children reflect the effects of traffic-related air pollution. Children with high
      immunoglobulin E levels appeared to be particularly susceptible to the effects of
      automobile exhaust.

PMID- 9012321
TI  - Longitudinal distribution of ozone absorption in the lung: effect of continuous
      inhalation exposure.
AB  - The effect of continuous exposure to ozone on the absorption of ozone in the
      conducting airways of human lungs was investigated with a bolus-response method.
      Eleven healthy nonsmoking college students (8 males, 3 females) were exposed at
      rest for 2 h on 3 separate days to air containing 0 ppm, 0.12 ppm, and 0.36 ppm
      ozone. A personal inhalation chamber equipped with a head-only clear plastic dome
      was used for exposure. Every 30 min a subject removed the dome and orally inhaled
      a series of five ozone-air boluses, each in a separate breath. Penetration of the
      boluses distal to the lips was targeted in the range of 70-120 ml (corresponding
      to the central conducting airways). By integrating the inhaled and exhaled-ozone
      concentration curves, we obtained the absorbed fraction (lambda) and the
      dispersion (sigma2) of the ozone bolus for each test breath. In addition, the
      subtraction of baseline measurements made just before exposure enabled us to
      determine the changes in absorbed fraction (deltalambda) and in dispersion
      (deltasigma2) that resulted from exposure alone. Absorbed fraction decreased, but
      sigma2 increased during O3 exposure, and the differences in deltalambda and in
      deltasigma2 between breathing air and exposure to either 0.12 ppm or 0.36 ppm O3
      were significant. We concluded that exposure of the conducting airways to O3
      reduced their capacity to absorb O3, possibly by the depletion of biochemical
      substrates that are normally oxidized by O3.

PMID- 9012322
TI  - Prediction equations for simple and visual two-choice reactions times in
      environmental neurotoxicology.
AB  - To provide preliminary prediction equations for simple visual and two-choice
      visual reactions times, timed from the appearance of the letter A or S on a
      computer screen to cancellation, we modeled 264 randomly selected subjects from
      voter registration rolls in Arizona and Louisiana. These predicted values,
      validated by comparison to observed values and coefficients, were compared with
      those from a second population in California. We tested ability to detect
      abnormality by measuring a trichloroethylene-exposed population aged 17-70 y. The
      natural logarithm of simple visual reaction time was independent of age and other
      factors. The natural logarithm of two-choice visual reaction time was increased
      by age. These equations predict performance of groups that are studied with
      respect to neurobehavioral effects of chemicals, and the equations distinguish
      exposure and nonexposure for the range of adult ages. To define abnormality of
      individual subjects, we suggest use of the predicted value, plus 1.5 standard
      deviations; in this study, 8% of the model group was selected as abnormal.

PMID- 9012323
TI  - Immunomodulatory effects of occupational exposure to mancozeb.
AB  - The effects of occupational exposure to ethylene-bis-dithiocarbamate of manganese
      and zinc on the immune system were evaluated in a group of mancozeb-exposed
      manufacturers and controls. The immune system tests revealed the following: (a)
      lymphocyte proliferative responses triggered by different activators and mitogen
      induced IL-2 production were higher in exposed subjects than in controls; (b)
      production of monocyte/macrophage-derived IL-1 and polyclonal IgG and IgM, by
      beta-lymphocytes, did not differ between exposed subjects and controls; (c)
      percentages and absolute numbers of total T-cells, T-helper cells, T
      suppressor/cytotoxic cells, activated T-cells, total beta-cells, and natural
      killer cells were similar in exposed subjects and controls; (d) serum
      immunoglobulin classes and complement fractions were within the range of
      normality; and (e) rheumatoid factor and non-organ-specific serum autoantibodies
      were absent in exposed and control subjects. An increase in T-cell functional
      response was found in the exposed group, suggesting a slight immunomodulator
      effect of mancozeb in conditions of low-level, prolonged occupational exposure.

PMID- 9012324
TI  - Fish consumption by Vietnamese women immigrants: a comparison of methods.
AB  - In this study, the measurement properties of an interview-administered fish
      consumption frequency questionnaire, used with a pilot study of 20 Vietnamese
      immigrant women, were described. Reproducibility across two summer interviews and
      one winter interview for estimates of seasonal and yearly intake of Great Lakes
      fish was moderate (intraclass correlation coefficients: .51-.61). Detailed
      questioning, by species, resulted in higher estimates of mean overall consumption
      (44.6-57.8 meals/y) than did asking about any fresh-water fish consumed (33.5
      46.1; differences 5.1-15.7). Estimates based on the fish consumption frequency
      questionnaire (i.e., 6.2+/-2.0 meals per winter season) were comparable with
      those based on extrapolation from a 1-mo calendar (5.8+/-5.6); however, both
      estimates of consumption were far less than a weighed record (29.1+/-22.2). The
      results of this study suggest that measurement variation in fish consumption
      estimates should be detailed in research reports and should be discussed with
      respect to risk assessments.

PMID- 9012325
TI  - High nitrate content in drinking water: cytogenetic effects in exposed children.
AB  - The potential genotoxicity of nitrates and nitrites-contaminants of drinking
      water that have been implicated in carcinogenesis-was investigated in this study.
      Sister chromatid exchanges and frequency of chromatid/chromosome aberrations were
      studied in peripheral blood lymphocytes of 70 children who were 12-15 y of age.
      These children were permanent residents in geographical areas of Greece, where
      elevated concentrations of nitrates (i.e., 55.70-87.98 mg/l) existed in drinking
      water. The control group comprised 20 healthy children who resided in areas with
      very low nitrate concentrations (i.e., 0.7 mg/l). A significant increase in the
      mean number of chromatid/chromosome breaks was observed in children exposed to
      nitrate concentrations that exceeded 70.5 mg/l (p < .01), but there was no
      significant increase in the mean number of sister chromatid exchanges per cell.
      The results indicate that chronic administration of elevated concentrations of
      nitrate in drinking water has the capability of inducing cytogenetic effects.

PMID- 9012326
TI  - Relationships between ferruginous bodies and uncoated asbestos fibers in lung
      tissue.
AB  - Tissue was obtained from two American groups. The tissue was defined by
      ferruginous body levels of either < or = 1000 or > 1000 ferruginous bodies/g dry
      weight, and tissue was evaluated by light microscopy and analyzed by analytical
      transmission electron microscopy. Tissue was bleach digested, and uncoated
      asbestos fibers were classified with respect to type and size. In addition, some
      ferruginous body cores were analyzed. There was a wide range of uncoated fibers
      associated with each ferruginous body. A relationship was found between amosite
      fibers and ferruginous bodies. Other asbestos types were not associated
      significantly with the development of ferruginous bodies. Uncoated crocidolite
      fibers were not detected in these samples; this result further emphasizes the
      under-appreciated exposure of Americans to amosite. The levels of ferruginous
      bodies in both groups suggest exposures above those expected in the general
      population. Uncoated chrysotile levels were below the ranges reported previously
      for some general populations. The data suggest that there is a wide variation in
      the ratio of uncoated to coated fibers and that the amphibole in the United
      States is more likely to be amosite than crocidolite.

PMID- 9012327
TI  - Renal effects of environmental lead in children.

PMID- 9012328
TI  - Childhood cancer rates in Canada.

PMID- 9012329
TI  - Association between prenatal lead (Pb) exposure, hematological parameters, and
      birth weight.

PMID- 9012330
TI  - Results of an epidemiologic study of acute myeloid leukemia (AML) incidence among
      Swedish petrol station attendants.

PMID- 9012331
TI  - Mortality rate among Cadmium (Cd)-exposed inhabitants was significantly higher
      than the entire Japanese population.

PMID- 9012332
TI  - Cancer-causing effects of pesticides.

PMID- 9012333
TI  - Lead concentration in bovine milk in India.

PMID- 9012334
TI  - Nasal septum lesions, skin lesions, and blood chemistry abnormalities in
      electroplate factory workers in Taiwan.

PMID- 9012336
TI  - [Hemipelvectomy due to blast injuries: possibilities of occupational
      rehabilitation].
AB  - A case of traumatic hemipelvectomy due to explosion of an antitank shell in a 21
      year-old Croatian Army soldier is described. Explosion was due to inadvertent
      handling of the shell in the army barracks. Literature data on persons who
      survived traumatic hemipelvectomy are extremely scarce; the injury is
      characterized by a very high death rate (60-100%). After prompt surgical
      treatment the patient developed a postoperative anaerobic clostridial infection.
      Owing to intensive clinical and physical therapy the patient was enabled for
      moving around in a special wheel-chair and walking with the help of crutches and
      a prosthesis. He was also enrolled in a training course in computer use.
      Continual physical therapy and psychotherapy were essential because of a high
      degree of disablement. Making the patient self-sufficient, fit for work and
      finding him an appropriate job is considered to be the responsibility not only of
      the professional medical team but also of joint efforts on the part of competent
      state ministries, Ministry of Defence, Ministry of Labour and Social Welfare,
      State Pension and Insurance Fund and Ministry of Education, Culture and Sports.

PMID- 9012335
TI  - Lead exposure of children from copper industry pollution.

PMID- 9012337
TI  - [Respiratory findings in textile workers employed in dyeing wool and cotton].
AB  - The prevalence of acute and chronic respiratory symptoms and diseases and
      ventilatory capacity were studied in 97 textile workers employed in dyeing wool
      and cotton fibres and in 76 non-exposed control workers. The prevalence of
      chronic respiratory symptoms was significantly higher in the textile workers
      compared to controls. The symptoms of occupational asthma were recorded in 7.2
      per cent of the textile workers. The prevalence of respiratory symptoms was
      higher in exposed smokers than in exposed non-smokers. The textile workers
      employed for more than 10 years had a higher prevalence of all respiratory
      symptoms than those with a shorter period of employment. The textile workers
      showed a high prevalence of acute symptoms which developed during work shift.
      Significant acute reductions of ventilatory capacity tests on maximum expiratory
      flow-volume curves (MEFV) in textile workers varied from 5.1% for FVC to 12.4%
      for FEF25. Ventilatory capacity tests in the textile workers before work shift
      were significantly diminished in comparison to the predicted values. Our data
      indicate that work in the textile dyeing industry may cause the development of
      respiratory symptoms and diseases as well as impairment of ventilatory capacity.

PMID- 9012338
TI  - [Exposure to low electromagnetic fields and the carcinogenesis process].
AB  - In the literature as well as in public media increasing attention is paid to
      possible health effects of exposure to low-frequency electric and magnetic
      fields, Experimental studies at the cellular level and mammalian studies in vivo
      have demonstrated various biological effects that are possibly associated with
      human exposure to low-frequency radiation. Although the exact mechanism of this
      relationship is not entirely clear, it has been indicated that low-frequency
      radiation might promote the process of carcinogenesis, although it does not seem
      likely to initiate it. A possible link between human low-frequency exposure and
      occurrence of carcinoma at child and adult age has been examined in some fifty
      epidemiological studies. A few studies have demonstrated a possible connection
      between carcinoma at child age and distance from electrical installations.
      Although the results point to an association between exposure to low-frequency
      electric and magnetic fields and cancer, further research is called for. In the
      meantime "cautious avoidance" of extended exposure to low-frequency
      electromagnetic fields is recommended.

PMID- 9012339
TI  - Dentistry on the couch.

PMID- 9012340
TI  - Anthropoid origins.
AB  - Recent fossil discoveries have greatly increased our knowledge of the morphology
      and diversity of early Anthropoidea, the suborder to which humans belong.
      Phylogenetic analysis of Recent and fossil taxa supports the hypotheses that a
      haplorhine-strepsirrhine dichotomy existed at least at the time of the earliest
      record of fossil primates (earliest Eocene) and that eosimiids (middle Eocene,
      China) are primitive anthropoids. Functional analysis suggests that stem
      haplorhines were small, nocturnal, arboreal, visually oriented insectivore
      frugivores with a scurrying-leaping locomotion. A change from nocturnality to
      diurnality was the fundamental adaptive shift that occurred at the base of the
      tarsier-eosimiid-anthropoid clade. Stem anthropoids remained small diurnal
      arborealists but adopted locomotor patterns with more arboreal quadrupedalism and
      less leaping. A shift to a more herbivorous diet occurred in several anthropoid
      lineages.

PMID- 9012341
TI  - Interdecadal Climate Fluctuations That Depend on Exchanges Between the Tropics
      and Extratropics
AB  - The unexpected and prolonged persistence of warm conditions over the tropical
      Pacific during the early 1990s can be attributed to an interdecadal climate
      fluctuation that involves changes in the properties of the equatorial thermocline
      arising as a result of an influx of water with anomalous temperatures from higher
      latitudes. The influx affects equatorial sea-surface temperatures and hence the
      tropical and extratropical winds that in turn affect the influx. A simple model
      demonstrates that these processes can give rise to continual interdecadal
      oscillations.

PMID- 9012342
TI  - Numerical Simulation of the Cretaceous Tethys Circumglobal Current
AB  - Certain paleobiogeographical reconstructions of ocean currents during the
      Cretaceous (about 144 to 65 million years ago) suggest that a circumglobal
      tropical current flowed westward through the continental configuration of that
      time. Although some numerical climate models failed in initial attempts to
      simulate this current, simulations with a coupled atmosphere-ocean model with
      relatively high spatial resolution and a late Cretaceous continental distribution
      show that a circumglobal current is a robust feature even though local surface
      currents in the Tethys Seaway reverse during the south Eurasian monsoon months.

PMID- 9012343
TI  - Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar
      membranes in distinct interhelical packing regimes.
AB  - Cationic liposomes complexed with DNA (CL-DNA) are promising synthetically based
      nonviral carriers of DNA vectors for gene therapy. The solution structure of CL
      DNA complexes was probed on length scales from subnanometer to micrometer by
      synchrotron x-ray diffraction and optical microscopy. The addition of either
      linear lambda-phage or plasmid DNA to CLs resulted in an unexpected topological
      transition from liposomes to optically birefringent liquid-crystalline condensed
      globules. X-ray diffraction of the globules revealed a novel multilamellar
      structure with alternating lipid bilayer and DNA monolayers. The lambda-DNA
      chains form a one-dimensional lattice with distinct interhelical packing regimes.
      Remarkably, in the isoelectric point regime, the lambda-DNA interaxial spacing
      expands between 24.5 and 57.1 angstroms upon lipid dilution and is indicative of
      a long-range electrostatic-induced repulsion that is possibly enhanced by chain
      undulations.

PMID- 9012344
TI  - The Water Dipole Moment in Water Clusters
AB  - The average dipole moment of a water molecule in the condensed phase is enhanced
      by around 40 percent relative to that of an isolated monomer. This enhancement
      results from the large polarization caused by the electric field induced by
      surrounding monomers. A quantitative molecular description of this polarization
      is essential for modeling aqueous solvation phenomena. This combined theoretical
      and experimental study of dipole moments in small water clusters provides such a
      description and also gives insights into the structure of liquid water.

PMID- 9012345
TI  - On the Quantum Nature of the Shared Proton in Hydrogen Bonds
AB  - The relative influence of thermal and quantum fluctuations on the proton transfer
      properties of the charged water complexes H5O2+ and H3O2- was investigated with
      the use of ab initio techniques. These small systems can be considered as
      prototypical representatives of strong and intermediate-strength hydrogen bonds.
      The shared proton in the strongly hydrogen bonded H5O2+ behaved in an essentially
      classical manner, whereas in the H3O2- low-barrier hydrogen bond, quantum zero
      point motion played a crucial role even at room temperature. This behavior can be
      traced back to a small difference in the oxygen-oxygen separation and hence to
      the strength of the hydrogen bond.

PMID- 9012346
TI  - Direct measurement of a tethered ligand-receptor interaction potential.
AB  - Many biological recognition interactions involve ligands and receptors that are
      tethered rather than rigidly bound on a cell surface. A surface forces apparatus
      was used to directly measure the force-distance interaction between a polymer
      tethered ligand and its receptor. At separations near the fully extended tether
      length, the ligands rapidly lock onto their binding sites, pulling the ligand and
      receptor together. The measured interaction potential and its dynamics can be
      modeled with standard theories of polymer and colloidal interactions.

PMID- 9012347
TI  - Fluorous synthesis: a fluorous-phase strategy for improving separation efficiency
      in organic synthesis.
AB  - Recovery and purification difficulties can limit the yield and utility of
      otherwise successful organic synthesis strategies. A "fluorous synthesis"
      approach is outlined in which organic molecules are rendered soluble in
      fluorocarbon solvents by attachment of a suitable fluorocarbon group.
      Fluorocarbon solvents are usually immiscible in organic solutions, and fluorous
      molecules partition out of an organic phase and into a fluorous phase in a
      standard liquid-liquid extraction. Simple yet substantive separations of organic
      reaction mixtures are achieved without resorting to chromatography. Because
      fluorous synthesis combines in many respects the favorable purification features
      of solid-phase synthesis with the favorable reaction, identification, and
      analysis features of traditional organic synthesis, it should prove valuable in
      the automated synthesis of libraries of individual pure organic compounds.

PMID- 9012348
TI  - Recharge in Volcanic Systems: Evidence from Isotope Profiles of Phenocrysts
AB  - Strontium isotope ratios measured from core to rim across plagioclase feldspar
      crystals can be used to monitor changes in the isotope composition of the magma
      from which they grew. In samples from three magma systems from convergent margin
      volcanoes, sudden changes in major element composition, petrographic features,
      and strontium isotope composition were found to correspond to discrete magmatic
      events, most likely repeated recharge of more mafic magma with lower ratios of
      strontium-87 to strontium-86 into a crustally contaminated magma.

PMID- 9012349
TI  - Selective use of TBP and TFIIB revealed by a TATA-TBP-TFIIB array with altered
      specificity.
AB  - Interaction between the TATA box-binding protein TBP and TFIIB is critical for
      transcription in vitro. An altered-specificity TBP-TFIIB interaction was
      rationally designed and linked in sequence to an altered-specificity TATA box-TBP
      interaction to study how TBP and TFIIB function together to support transcription
      in human cells. The activity of this altered-specificity TATA-TBP-TFIIB array
      demonstrated that many activators use the known TBP-TFIIB interaction to
      stimulate transcription. One activator, however, derived from a glutamine-rich
      activation domain of Sp1, activated transcription independently of this
      interaction. These results reveal that selectivity in activator function in vivo
      can be achieved through differential use of TBP and TFIIB.

PMID- 9012350
TI  - Positional cloning of a gene for nematode resistance in sugar beet.
AB  - The Hs1(pro-1) locus confers resistance to the beet cyst nematode (Heterodera
      schachtii Schmidt), a major pest in the cultivation of sugar beet (Beta vulgaris
      L.). The Hs1(pro-1) gene was cloned with the use of genome-specific satellite
      markers and chromosomal break-point analysis. Expression of the corresponding
      complementary DNA in a susceptible sugar beet conferred resistance to infection
      with the beet cyst nematode. The native Hs1(pro-1) gene, expressed in roots,
      encodes a 282-amino acid protein with imperfect leucine-rich repeats and a
      putative membrane-spanning segment, features similar to those of disease
      resistance genes previously cloned from higher plants.

PMID- 9012351
TI  - Two modulatory effects of attention that mediate object categorization in human
      cortex.
AB  - Attentional modulation of cortical activity was examined by varying the rate of
      visual stimuli in object categorization tasks according to single and conjoined
      features. Activation of dorsolateral frontal cortex was independent of the
      stimulus presentation rate and elicited by the participant's attention to
      conjoined compared with single features. Several cortical regions showed
      attentionally modulated activity. In inferior temporal cortex, modulation was due
      to an additional bias signal underlying normal rate-correlated activity. In two
      other regions (premotor cortex and cerebellum), attention modified the
      correlation of activity and the stimulus presentation rate. Attentional effects
      in the human cortex are expressed by at least two physiologically distinct
      mechanisms acting on spatially distributed areas.

PMID- 9012352
TI  - Dopaminergic neurons protected from degeneration by GDNF gene therapy.
AB  - Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival
      of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector
      encoding human GDNF injected near the rat substantia nigra was found to protect
      DA neurons from the progressive degeneration induced by the neurotoxin 6
      hydroxydopamine (6-OHDA) injected into the striatum. Ad GDNF gene therapy reduced
      loss of DA neurons approximately threefold 6 weeks after 6-OHDA lesion, as
      compared with no treatment or injection of Ad lacZ or Ad mGDNF (encoding a
      biologically inactive deletion mutant GDNF). These results suggest that Ad vector
      mediated GDNF gene therapy may slow the DA neuronal cell loss in humans with
      Parkinson's disease.

PMID- 9012353
TI  - Paradoxical improvement of impulse conduction in cardiac tissue by partial
      cellular uncoupling.
AB  - Generally, impulse propagation in cardiac tissue is assumed to be impaired by a
      reduction of intercellular electrical coupling or by the presence of structural
      discontinuities. Contrary to this notion, the spatially uniform reduction of
      electrical coupling induced successful conduction in discontinuous cardiac tissue
      structures exhibiting unidirectional conduction block. This seemingly paradoxical
      finding can be explained by a nonsymmetric effect of uncoupling on the current
      source and the current sink in the preparations used. It suggests that partial
      cellular uncoupling might prevent the initiation of cardiac arrhythmias that are
      dependent on the presence of unidirectional conduction block.

PMID- 9012354
TI  - Calcium waves in retinal glial cells.
AB  - Calcium signals were recorded from glial cells in acutely isolated rat retina to
      determine whether Ca2+ waves occur in glial cells of intact central nervous
      system tissue. Chemical (adenosine triphosphate), electrical, and mechanical
      stimulation of astrocytes initiated increases in the intracellular concentration
      of Ca2+ that propagated at approximately 23 micrometers per second through
      astrocytes and Muller cells as intercellular waves. The Ca2+ waves persisted in
      the absence of extracellular Ca2+ but were largely abolished by thapsigargin and
      intracellular heparin, indicating that Ca2+ was released from intracellular
      stores. The waves did not evoke changes in cell membrane potential but traveled
      synchronously in astrocytes and Muller cells, suggesting a functional linkage
      between these two types of glial cells. Such glial Ca2+ waves may constitute an
      extraneuronal signaling pathway in the central nervous system.

PMID- 9012355
TI  - Joining the two domains of a group I ribozyme to form the catalytic core.
AB  - Self-splicing group I introns, like other large catalytic RNAs, contain
      structural domains. Although the crystal structure of one of these domains has
      been determined by x-ray analysis, its connection to the other major domain that
      contains the guanosine-binding site has not been known. Site-directed mutagenesis
      and kinetic analysis of RNA splicing were used to identify a base triple in the
      conserved core of both a cyanobacterial (Anabaena) and a eukaryotic (Tetrahymena)
      group I intron. This long-range interaction connects a sequence adjacent to the
      guanosine-binding site with the domain implicated in coordinating the 5' splice
      site helix, and it thereby contributes to formation of the active site. The
      resulting five-strand junction, in which a short helix forms base triples with
      three separate strands in the Tetrahymena intron, reveals exceptionally dense
      packing of RNA.

PMID- 9012356
TI  - The effect of diabetes mellitus on endocrine and reproductive function.
AB  - The adverse effects of diabetes on the circulatory, visual, renal, and peripheral
      nervous system are commonly recognized and have been extensively studied. The
      effects of decreased insulin secretion or resistance to insulin action on
      endocrine glands have not been as carefully documented. Both clinical and animal
      research have demonstrated that diabetes mellitus is commonly associated with
      altered thyroid, adrenal and gonadal function. Some of these changes are reversed
      with insulin replacement therapy, but endocrine function is not always restored
      to normal even with rigorous glycemic control. Patients with poorly controlled
      diabetes exhibit basal and stimulated growth hormone (GH) hypersecretion, while
      patients with good metabolic control still present with diurnal and exercise
      induced GH hypersecretion. In contrast, diabetes suppresses GH secretion in the
      rat. It is unclear why GH secretion is altered, but clinical and experimental
      evidence exists for diabetes-associated changes in GH-releasing hormone and
      somatostatin release as well as for changes in the pituitary response to these
      hypothalamic hormones. The thyroid hormones, T3 and T4, are usually suppressed in
      both humans and experimental animals with diabetes. This effect of diabetes
      appears to involve changes in hypothalamic thyrotropin-releasing hormone (TRH)
      secretion as well as changes in pituitary thyrotropin (TSH) release and direct
      effects at the level of the thyroid gland. Adrenal cortical function is often
      enhanced in diabetes, most likely due to alterations in glucocorticoid feedback
      responses. There is much conflicting data on adrenal medullary function in
      diabetes; responses to stress and exercise, however, are often abnormal. Finally,
      male and female reproductive function is often disrupted in diabetes. Data from
      animal studies suggest that the major cause is altered hypothalamic LHRH
      secretion secondary to diabetes-induced changes in hypothalamic neurotransmitter
      metabolism.

PMID- 9012357
TI  - Asbestosis: clinical spectrum and pathogenic mechanisms.
AB  - Asbestosis is a diffuse pulmonary fibrotic process caused by the inhalation of
      asbestos fibers. Despite extensive investigations, the precise mechanisms
      regulating asbestos-induced lung damage are not fully understood. This review
      summarizes the important clinical manifestations and pathogenic mechanisms of
      asbestosis. We focus on the relatively new information that has emerged over the
      last several years. The diagnosis of asbestosis is often easily established by
      well-characterized criteria. Pulmonary physiologic testing and high-resolution
      computed tomography can detect clinically occult disease. The finding of asbestos
      bodies in the bronchoalveolar lavage fluid confirms that an individual has been
      exposed to asbestos but is of unclear significance in diagnosing asbestosis.
      Evidence reviewed herein suggests that asbestos pulmonary toxicity is due in part
      to the physical properties of the fibers, iron-catalyzed reactive oxygen species
      (ROS), and macrophage-derived cytokines and growth factors. Special emphasis is
      given to the hypothesis that iron-catalyzed hydroxyl radicals (HO.-) have a
      pivotal role in causing asbestosis. Definitive proof of this hypothesis is
      difficult to obtain since HO.- are highly reactive and their deleterious effects
      to cells may have occurred years prior to disease presentation. Despite these
      limitations, considerable data firmly support the notion that ROS have an
      important role in causing asbestos toxicity. Further, the iron content of
      asbestos or the redoxactive iron associated with or mobilized from the surface of
      the fibers is important in generating HO.- as well as in activating inflammatory
      cells. There also appears to be a close association between asbestos-induced ROS
      production and cellular toxicity and DNA damage. The full expression of asbestos
      induced diseases likely involves the contribution of cytokines, growth factors,
      proteases, and other inflammatory cell products. Many of the mechanisms by which
      asbestos- and inflammation-induced ROS activate specific genes in pulmonary cells
      remain to be elucidated.

PMID- 9012358
TI  - Role of transforming growth factor-beta in tissue injury and repair.
AB  - Transforming growth factor-beta (TGFbeta) belongs to a family of multifunctional
      polypeptides which regulate normal cell growth, development, and tissue
      remodeling following injury. The ability of cells to produce TGFbeta or to
      respond to this growth factor via cell surface receptors is highly conserved
      throughout the animal kingdom. TGFbeta is a potent growth inhibitor of many
      normal and transformed cell lines; abnormalities in TGFbeta signaling have been
      linked to tumorigenicity. Disruption of the TGFbeta1 gene in utero produces a
      wasting syndrome characterized by systemic inflammation, suggesting that this
      growth factor plays an important role in limiting the inflammatory response.
      TGFbeta is a dominant mediator of the pathologic extracellular matrix
      accumulation that characterizes progression of tissue injury to end-stage organ
      failure. Recent studies directed towards characterization of the TGFbeta genes,
      dissection of the mechanisms by which TGFbetas are produced and activated, and
      identification of TGFbeta signaling pathways have established the important roles
      that these family members play in cell and tissue homeostasis. In this overview,
      TGFbeta structure-function relationships and their relevance to a few select
      models of tissue injury/wound repair are highlighted.

PMID- 9012359
TI  - Autoreactive T-cell clones from the nonobese diabetic mouse.
AB  - The availability of cloned lines of T cells reactive with islet antigens has
      provided investigators with new tools to study how T cells contribute to
      autoimmune disease. T-cell clones isolated from the diabetes-prone nonobese
      diabetic (NOD) mouse are proving to be particularly valuable for analyzing
      pathogenesis and hold great promise for determining which T-cell subsets are
      involved in beta-cell destruction versus immunoregulation of the inflammatory
      process. Diabetogenic T-cell clones have been mostly of the CD4+, Th1 phenotype,
      but CD8+ T cell clones are also capable of transferring disease. In some cases, T
      cell lines and clones (CD4+ and CD8+) have been found to have protective
      properties. In general T-cell antigen specificities have not been defined, as
      islet cells or lysates were used as the selecting antigen. However, there is an
      increasing number of reports of T cells specific for defined islet proteins, such
      as insulin and GAD, and some of these lines can induce disease. The variety of T
      cell clones that have been produced indicate that there may a variety of
      conditions that lead to or protect against beta-cell destruction and provide
      further evidence that autoantigens are generated during development of disease.

PMID- 9012360
TI  - Mesenchymal-epithelial interactions in an in vitro model of neonatal mouse
      uterus.
AB  - Stromal factors have been implicated in epithelial growth of the fetal and
      neonatal mouse uterus, as well as in uterine epithelial proliferation in the
      adult. In the neonate, uterine growth is independent but responsive to estrogen,
      while epithelial proliferation in the adult uterus is hormonally regulated. A co
      culture model was developed to study interactions between uterine epithelium and
      stroma. Uteri of neonatal mouse were enzymatically separated into epithelial and
      mesenchymal cell fractions, and these were cultured for 5 days on Millipore well
      inserts, either separately or in co-culture on opposite sides of the insert
      membrane. When epithelial cells were grown alone, inclusion of serum in the
      culture medium tripled the number of cells present after 3-5 days compared with
      serum-free medium. Co-culture in the presence or absence of serum resulted in a 5
      fold increase in epithelial cell number after 5 days. Addition of estrogen had no
      significant effect on epithelial cell number regardless of the presence of
      mesenchyme. Epithelial cultures grown in medium conditioned by mesenchymal cells
      exhibited an intermediate increase in cell number. We therefore conclude that
      uterine mesenchyme from neonatal mouse produces a diffusible factor that enhances
      the growth of the overlying epithelium; however, whether the mesenchyme has a
      role in estrogen-stimulated epithelial proliferation has not been definitively
      ascertained.

PMID- 9012361
TI  - Overexpression of the heme oxygenase gene in renal cell carcinoma.
AB  - Heme oxygenase (HO) activity has been implicated in the regulation of renal
      function and cell growth in normal and disease states. Expression of HO genes has
      been shown to regulate important hemoprotein(s) such as cytochrome P450. In the
      present study, HO activity was measured in samples of human adenocarcinoma,
      juxtatumor, and normal renal tissues. The samples were histologically examined to
      verify the malignant and normal nature. HO activity was 4-fold higher in the
      adenocarcinoma than in either normal or juxtatumor tissues. We designed a reverse
      transcriptase-polymerase chain reaction (RT-PCR) method to assess the presence of
      HO-1 and HO-2 mRNA in biopsy samples of various human renal tissues. Total RNA
      from renal samples was reverse transcribed and amplified simultaneously by PCR
      using specific primers for HO-1 and HO-2. Results show that both HO-1 and HO-2
      mRNAs were expressed in all renal tissues examined and that HO-1 appeared to be
      amplified more than HO-2. Northern blot analysis revealed that HO-1 mRNA was
      elevated by several-fold in adenocarcinoma compared with juxtatumor or normal
      tissues. In contrast, no differences in HO-2 mRNA levels were observed using
      either RT-PCR or Northern blot. Cytochrome P450 arachidonic acid epoxygenase and
      omega-hydroxylase activities were markedly reduced in the tumor tissues, whereas,
      in the juxtatumor tissue, cytochrome P450 omega-hydroxylase activity was
      significantly increased. Northern blot analysis using cytochrome P450 cDNA probe
      4A2 cDNA for the omega-hydroxylase gene family revealed that mRNA levels for
      omega-hydroxylase transcripts were significantly decreased in the adenocarcinoma
      compared with juxtatumor. The decrease in cytochrome P450 4All mRNA levels
      correlated with a decrease in the arachidonic acid omega-hydroxylation
      metabolite, 20-HETE. The production of 20-HETE was significantly higher in
      juxtatumor in agreement with omega-hydroxylase mRNA. Higher levels of HO-1 may be
      a contributing factor for the undetectable levels of cytochrome P450 arachidonic
      acid metabolites, 20-HETE, in the adenocarcinoma. Our results suggest that
      increased generation of mitogenic activities by omega-hydroxylase and 20-HETE in
      the juxtatumor may be a contributing factor in the development and growth of
      neoplastic tissues, and the induction of HO in the tumor tissue may be an attempt
      to limit oxidative injury caused by the cytochrome P450 metabolites and other
      oxidative stress.

PMID- 9012362
TI  - Dietary cholesterol metabolism in Japanese quail lines selected for plasma
      cholesterol levels.
AB  - Dietary cholesterol metabolism was studied, using a single dose of emulsion, per
      os (test meal), in lines of Japanese quail that were divergently selected for
      high (HL) and low (LL) plasma total cholesterol. The meal contained [3H]
      cholesterol, [14C] beta-sitosterol, unlabeled cholesterol, triolein, and bile
      salt. Recovery of the nonabsorbable beta-sitosterol in the excreta permitted
      determination of the percentage of cholesterol absorbed. The amounts of [3H] in
      the plasma, egg yolks, and the excreta neutral and acid sterols were determined.
      A line-x-time interaction for [3H] in plasma indicated that the level of plasma
      cholesterol derived from the test meal declined more rapidly in the LL than in
      the HL. The higher [3H] detected in the excreta acidic sterols of the LL 12 hr
      after the test meal indicated that bile acid excretion of cholesterol was greater
      in the LL than in the HL. There were no differences in cholesterol absorption
      between lines or sexes. Cumulative [3H] radioactivity in the eggs over 18 days
      following the test meal was higher in the HL yolks; however, this line effect was
      due to the greater number of eggs produced by the HL. Thus, one of the mechanisms
      by which the LL maintains low plasma cholesterol levels is by an enhanced
      excretion of bile acid compared with the HL. The data also suggest that the more
      severe atherogenic effect of dietary cholesterol observed in the HL could be, in
      part, due to the longer residence time of cholesterol in circulation.

PMID- 9012363
TI  - Psychoactive cannabinoids increase mortality and alter acute phase cytokine
      responses in mice sublethally infected with Legionella pneumophila.
AB  - Marijuana contains both psychoactive and nonpsychoactive cannabinoids which have
      varying effects on the immune response system. Previous studies with delta-9
      tetrahydrocannabinol (THC), the major psychoactive component of marijuana, showed
      that this substance augmented the susceptibility of mice to infection with the
      opportunistic pathogen Legionella pneumophila. The present study compared the
      enhancement of Legionella-induced mortality in mice due to two other major of
      marijuana components, cannabinol and cannabidiol, as well as the synthetic
      psychoactive cannabinoid CP 55,940. Inbred BALB/c mice, relatively resistant to
      infection with Legionella, were given the marijuana component 1 day before and 1
      day after a sublethal intravenous infection with Legionella. Unlike the effect of
      THC, an 8 mg/kg dose of either cannabinol or cannabidiol did not affect mortality
      of the mice sublethally infected with Legionella. Mice given a 16 mg/kg dose of
      these components of marijuana, however, showed a slight to moderately increased
      mortality following the sublethal infection with Legionella. In contrast, a dose
      of 6 mg/kg of the synthetic psychoactive cannabinoid CP 55,940 given 1 day before
      and 1 day after infection with Legionella resulted in about 50% of the animals
      dying, the same level of augmentation of lethality induced by THC. Liver, spleen,
      and lung tissues were removed from the surviving mice 24 hr after the second THC
      injection and tested for the presence of viable Legionella using a standard CFU
      assay. The mice injected with THC before and after infection showed significantly
      higher levels of bacteria in their lung than mice that were not given any
      cannabinoid but were infected sublethally with the Legionella. Mice injected with
      the other cannabinoids, including the synthetic cannabinoid, showed a much
      smaller increase in the number of Legionella in their lung when infected with
      Legionella and treated with the drug. The number of bacteria recovered from the
      kidney and liver of the mice regardless of treatment with a cannabinoid,
      including with THC, did not show significant changes. RNA isolated from the
      spleen of the THC- and Legionella-treated animals was examined to determine at
      the molecular level whether acute phase pro-inflammatory cytokines (i.e., IL-1,
      IL-6 and TNF-alpha) were altered following drug treatment and infection, since
      previous studies had shown there were increased serum levels of these cytokines
      in the mice. It was found that the mRNA levels for IL-1 remained generally
      constant regardless of whether the infected animals were treated with a
      cannabinoid. However, the mRNA level for IL-6 was markedly increased following
      treatment of the infected animals with THC, suggesting the possible involvement
      of this pro-inflammatory cytokine in increased mortality. The mRNA level for TNF
      alpha was generally low and not significantly altered in the drug treated
      animals. Mice given other cannabinoids, including cannabinol and cannabidiol, as
      well as the synthetic CP 55,940, showed no significant change in the level of
      mRNA for any of the cytokines tested.

PMID- 9012364
TI  - Intracranial-extracranial differences in the Ca2+ sensitivity of rabbit arteries.
AB  - We have previously demonstrated that the ratio of calcium uptake to force
      production varies widely with age, artery size, and method of contraction in
      cerebral arteries. The present experiments were conducted to examine the
      possibility that these differences involve corresponding variations in
      contractile force-calcium relations. Common carotid (COM), basilar (BAS), and
      middle cerebral (MCA) arteries from adult were denuded of endothelium and mounted
      in vitro for measurement of contractility. Following equilibration at optimum
      resting diameter, the arteries were permeabilized (beta-escin, 50 microg/ml) and
      depleted of intracellular Ca2+ by treatment with 1 microM A23187. Ca2+ depletion
      was verified by absence of any contracile response to either 25 mM caffeine or 1
      microM inositol 1,4,5-trisphosphate. Then, in the continuous presence of 1 microM
      calmodulin, bath calcium concentration was raised from zero through 10 microM in
      half-log increments and the corresponding contractions were recorded. For all
      permeabilized arteries, the maximum force produced by 10 microM Ca was greater
      than or equal to that produced by 120 mM potassium-Krebs in the same segment
      before skinning. The pD2 (-log ED50) values for calcium averaged 6.39 +/- 0.03,
      6.77 +/- 0.04, and 6.92 +/- 0.03 in COM, BA, and MCA segments, respectively. In
      arteries contracted by a constant submaximal concentration of calcium (0.1 microM
      for BAS and MCA, 0.3 microM for COM), the addition of 5HT produced a dose
      dependent and GDPbetaS-sensitive increase in tension of up to 44% maximum.
      GTPgammaS mimicked the effects of 5HT and prevented further increases in Ca force
      induced by 5HT. Together, these data demonstrate that cerebrovascular calcium
      sensitivity is an anatomically heterogenous, physiologically regulated parameter
      responsive to agonist-induced perturbations.

PMID- 9012365
TI  - Effect of somatostatin on the release of gonadotropins in male rats.
AB  - Since somatostatin, the growth hormone release-inhibiting hormone, has inhibitory
      actions in many cell types and is delivered to the anterior pituitary gland via
      the hypophysial portal vessels, as well as being synthesized by cells within the
      gland, we tested the hypothesis that it might inhibit the release of
      gonadotropins from anterior pituitaries in vitro. Consequently, the effect of
      somatostatin on gonadotropin release from incubated anterior pituitaries of male
      rats with and without the stimulatory action of luteinizing hormone-releasing
      hormone (LHRH) was studied. After a preincubation period of 1 hr, hemipituitaries
      from adult male rats were incubated in fresh Krebs-Ringer bicarbonate (KRB)
      buffer in a Dubnoff incubator with an atmosphere of 95% O(2)-5% CO2 at 37 degrees
      C for 3 hr. Incubation with somatostatin (10(-6), 10(-7), and 10(-8) M) had no
      effect on basal release of either LH or follicle-stimulating hormone (FSH).
      However, somatostatin (10(-6)-10(-8) M) suppressed LHRH (1.7 x 10(-8) M)-induced
      release of LH (P < 0.01 to P < 0.0001), but not FSH. Furthermore, somatostatin
      antiserum (1:1000) had no significant effect on basal LH or FSH release, whereas
      incubation with the antiserum plus LHRH (1.7 x 10(-9) or 1.7 x 10(-8) M)
      increased LH (P = 0.015 and P=.005, respectively), but not FSH release. In
      summary, our results suggest that somatostatin exerts a physiologically
      significant inhibitory effect on LH but not FSH release in the presence of LHRH
      in vitro. Presumably, somatostatin is secreted in vitro by pituitary cells since
      not only have anterior pituitaries of rats been shown to contain somatostatin,
      but also somatostatin mRNA. Somatostatin then diffuses to the LH gonadotropes,
      where it exerts its inhibitory action. However, the release of somatostatin is
      insufficient to alter basal in vitro release. On the other hand, at least at the
      concentrations employed, there was no significant effect either of somatostatin
      or the antiserum to alter basal or stimulated FSH release.

PMID- 9012366
TI  - Prevention of retrovirus-induced aberrant cytokine secretion, excessive lipid
      peroxidation, and tissue vitamin E deficiency by T cell receptor peptide
      treatments in C57BL/6 mice.
AB  - To test whether T cell receptor (TCR) peptide treatment can prevent immune
      dysfunction, excessive lipid peroxidation, and malnutrition caused by retrovirus
      infection, female C57BL/6 mice were infected with LP-BM5 retrovirus. Infection
      with retrovirus inhibited lymphocyte proliferation, cytokine release T helper 1
      cells, stimulated cytokine secretion by T helper 2 cells, induced abnormal
      hepatic and cardiac lipid profiles, and produced excessive tissue lipid
      peroxidation with hepatic and cardiac vitamin E deficiency. Two weeks after
      infection, TCR peptides Vbeta5.2, Vbeta8.1, Vbeta8.1 + Vbeta5.2, Vbeta8.1(N), and
      Vbeta8.1 were injected to the mice at dose of 200 microg/mouse. Vbeta8.1 and
      Vbeta5.2 treatments largely maintained lymphocyte proliferation and IL-2 and IFN
      gamma release, and prevented excessive IL-6, IL-10, and TNF-alpha secretion.
      Concomitantly, these treatments normalized hepatic and cardiac lipid profiles,
      reduced tissue lipid peroxidation, and thereby significantly maintained vitamin E
      in the liver and heart. Vbeta8.1 segments treatment did not prevent the immune
      dysfunction, abnormal lipid profile and lipid peroxidation, and vitamin E
      deficiency caused by the retrovirus infection. In conclusion, injection of intact
      TCR peptides during murine retrovirus infection largely prevented immune
      dysfunction by blocking the excessive stimulation of a T cell subset caused by
      retroviral superantigens. It also ameliorated malnutrition status by normalizing
      lipid profile, lipid peroxidation, and vitamin E deficiency. T cell immune
      dysfunction and its prevention by TCR peptide treatment is important in the
      therapy of vitamin E deficiency induced by retrovirus infection.

PMID- 9012367
TI  - The central nervous system and exposure to toluene: a risk characterization.
AB  - The principal health outcome of exposure to toluene is dysfunction of the central
      nervous system. Effects range from fatalities and severe neurological disorders
      in toluene abuse situations to deficits in neurobehavioral function in
      occupational populations. An Inhalation Reference Concentration (RfC) of 0.4 mg
      toluene/m3 or 0.1 ppm was developed by the U.S. EPA to protect general
      populations chronically exposed to toluene. The RfC was derived from results of
      an occupational study involving Asian workers who developed neurobehavioral
      deficits at a mean toluene exposure level at the time of the study of 88 ppm. The
      derivation incorporated several uncertainty factors, one of which was a factor of
      10 to account for sensitive subpopulations. Recent evidence indicates that some
      Japanese and possibly other Asian populations harbor a defective gene for
      aldehyde dehydrogenase, and thus exhibit a decreased rate of toluene metabolism.
      Although it is not known if reduced metabolism by aldehyde dehydrogenase also was
      a factor in the occupational study, preshift blood levels of toluene were
      considerably higher than preshift levels from non-Asian workers exposed to
      similar air levels of toluene. The elevated blood levels are consistent with
      defective metabolism but remain to be confirmed. Inasmuch as air levels of
      toluene in urban environments are about 10-fold lower than the RfC, an adequate
      measure of protection is afforded by the RfC with or without an uncertainty
      factor for sensitive subgroups. However, the uncertainty factor for sensitive
      subgroups should be retained because there is no information regarding toluene
      metabolism in children.

PMID- 9012368
TI  - Association between lifetime ambient ozone exposure and pulmonary function in
      college freshmen--results of a pilot study.
AB  - Human health effects due to chronic exposure to ozone (O3) have not been
      established due to problems with exposure assignment and the use of measures of
      lung function which may not reflect the site of O3 toxicity in the lung. We
      investigated the feasibility of retrospective assessment of O3 exposure-relevant
      covariates and derived lifetime "effective exposure" to ozone. Mid- and end
      expiratory flows (FEF25-75%, FEF75%) were regressed against effective exposure
      and ecological lifetime exposure. A convenience sample of 130 UC Berkeley
      freshmen, ages 17-21, participated twice in the same tests (residential history,
      questionnaire, pulmonary function), 5-7 days apart. Students had to be lifelong
      residents of Northern (SF) or Southern (LA) California. Monthly ambient O3
      concentrations (OZ) were assigned based on the lifetime residential history. An
      "effective time" (T) spent in OZ environments was derived for each residence and
      age stratum (0-2, 3-5, 6-11, 12+) with the use of questions about "total time
      spent outdoors" and time spent in "moderate" and/or "heavy" activity. Effective
      exposure was calculated over the lifetime (OZ x T) of each subject. Ozone metrics
      used were 8-hr averages (10 AM-6 PM) and "hours above 60 ppb." FEF25-75% and
      FEF75% decreased with both effective exposure and ecologic assignment of O3
      exposure. For a 20 ppb increase (interquartile range) in 8-hr O3, FEF75%
      decreased 334 ml/sec (95%Cl:11-657 ml/sec), which corresponds to 14% (1.0-28.3%)
      of the population mean FEF75%. The corresponding effect on FEF25-75% was -420
      ml/sec (95%Cl: +46 to -886, P = 0.08) or 7.2% of the mean. Use of time-activity
      data to define exposure had no impact on estimates. Negative confounding factors
      were region (SF vs LA), gender, and ethnicity. Lifetime 8-hr average O3
      concentrations ranged from 16 to 74 ppb with little overlap between regions.
      There was no evidence for different O3 effects across regions. Effects were
      independent of lifetime mean PM10, NO2, temperature, or humidity. Effects on FEV1
      tended to be negative whereas those for FVC, although negative in some models,
      where inconsistent and small. The strong relationship of lifetime ambient O3 on
      mid- and end-expiratory flows of college freshmen and the lack of association
      with FEV1 and FVC are consistent with biologic models of chronic effects of O3 in
      the small airways. Since the present study was designed as a pilot study, these
      findings have to be confirmed in a larger sample that is representative of the
      target population.

PMID- 9012369
TI  - Association between ozone and hospitalization for respiratory diseases in 16
      Canadian cities.
AB  - The effects of tropospheric ozone on lung function and respiratory symptoms have
      been well documented at relatively high concentrations. However, previous
      investigations have failed to establish a clear association between tropospheric
      ozone and respiratory diseases severe enough to require hospitalization after
      controlling for climate, and with gaseous and particulate air pollution at the
      lower concentrations typically observed in Canada today. To determine if low
      levels of tropospheric ozone contribute to hospitalization for respiratory
      disease, air pollution data were compared to hospital admissions for 16 cities
      across Canada representing 12.6 million people. During the 3927-day period from
      April 1, 1981, to December 31, 1991, there were 720,519 admissions for which the
      principle diagnosis was a respiratory disease. After controlling for sulfur
      dioxide, nitrogen dioxide, carbon monoxide, soiling index, and dew point
      temperature, the daily high hour concentration of ozone recorded 1 day previous
      to the date of admission was positively associated with respiratory admissions in
      the April to December period but not in the winter months. The relative risk for
      a 30 ppb increase in ozone varied from 1.043 (P < 0.0001) to 1.024 (P = 0.0258)
      depending on the selection of covariates in the regression model and subset of
      cities examined. The association between ozone and respiratory hospitalizations
      varied among cities, with relative risks ranging from 1.000 to 1.088 after
      simultaneous covariate adjustment. Particulate matter and carbon monoxide were
      also positively associated with respiratory hospitalizations. These results
      suggest that ambient air pollution at the relatively low concentrations observed
      in this study, including tropospheric ozone, is associated with excess admissions
      to hospital for respiratory diseases in populations experiencing diverse climates
      and air pollution profiles.

PMID- 9012370
TI  - Studies on the mutagenicity of mild gasification products of coal and their
      subfractions by the Salmonella/microsomal assay.
AB  - Mild gasification of coal is a technology being developed in the United States in
      order to upgrade lower rank coals and facilitate their use in coal-burning
      electric generation plants. Thirteen coal-derived mild gasification products from
      different coal sources and processing conditions have been examined for their
      potential biohazards. The mutagenicity of these samples was tested with the Ames
      Salmonella/microsomal assay. Two solvents, dimethyl sulfoxide (DMSO) and
      polyoxyethylene-sorbitan monooleate (Tween 80), were used to dissolve samples in
      a manner to facilitate their interaction with the test organisms. The results
      showed that 9 of the 13 samples displayed mutagenic activity in test strains TA98
      and/or TA100 with or without metabolic activation, whether dissolved in Tween 80
      or DMSO. Five mutagenic and two nonmutagenic samples were class-fractionated into
      basic, acidic, nonpolar, and polar neutral subfractions to examine their class
      related mutagenic activities. Results of the testing of subfractions of the five
      mutagenic and one nonmutagenic samples showed mutagenic activity in at least the
      nonpolar neutral fraction. The subfractions of the another nonmutagenic sample
      did not display any mutagenic activity. Chemical characterization of the
      subfractions revealed the existence of aromatic hydrocarbons in certain
      subfractions, which may be responsible for the mutagenic activity of the coal
      derived mild gasification products.

PMID- 9012371
TI  - Lead-calcium interactions: involvement of 1,25-dihydroxyvitamin D.
AB  - Interactions between dietary calcium (Ca) and lead (Pb) which influence serum
      levels of the vitamin D hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D), intestinal
      Ca and Pb absorption, and body Pb retention were investigated in chicks. In a 5 x
      5 (levels of Ca and Pb) design, response surface modeling was used to describe
      and compare the various interactions. Lead ingestion and Ca deficiency alone or
      in combination generally increased serum 1,25(OH)2D levels over most of the range
      of dietary Ca and Pb. However, in severe Ca deficiency, Pb ingestion resulted in
      marked decreases in hormone concentration. Overall similarities in response
      profiles for 1,25(OH)2D, intestinal Ca absorption and calbindin-D suggest that
      major interactions between Pb and Ca are mediated via changes in circulating
      1,25(OH)2D concentration, rather than direct effects on the intestine. The
      response profiles for Ca and Pb absorption differed, in part, suggesting that
      intestinal transport of the two cations may not be identical. Kidney and bone Pb
      content also differed in response to varying Ca and Pb levels, providing evidence
      for additional tissue-specific interactions not related to 1,25(OH)2D. The
      present study provides a comprehensive basis on which to interpret the results of
      previous clinical and experimental results.

PMID- 9012372
TI  - The effects of methoxychlor on early sea urchin development.
AB  - Methoxychlor (MXC) is a widely used pesticide which has been found in water
      sources near agricultural sites. Embryos of aquatic organisms are likely to
      encounter MXC due to land runoff. The sea urchin embryo (Strongylocentrotus
      purpuratus) was used as a model system to document the effects of MXC on early
      development up to the pluteus stage. Fertilized eggs and embryos were exposed to
      several concentrations (0.1, 1.0, 10, and 100 ppm) of the pesticide in both
      chronic and acute exposure regimens. With chronic exposure, percentages of
      embryos completing normal first cleavage decreased with increased concentrations
      of MXC, and subsequent cleavages became even more irregular in that blastomeres
      divided asymmetrically and asynchronously. Ten parts per million MXC allowed
      development through the hatched blastula stage, whereas embryos in 100 ppm MXC
      did not hatch. In acute exposure trials, fertilized eggs were pulsed (i.e.,
      exposed for brief durations) to MXC for 30, 60, or 90 min. The MXC was then
      washed out. Recovery of normal development was proportional to the amount and
      duration of MXC exposure. Development was delayed in embryos exposed to 100 ppm
      MXC for 30 or 60 min. The embryos exposed to 100 ppm MXC for 90 min were abnormal
      as early as the four-cell stage, and by 72 hr more than 90% had abnormal gut
      development, indicating disruption of gastrulation. These data show that MXC
      exposure resulted in retardation of cleavage and abnormal gastrulation, basic
      morphogenetic processes.

PMID- 9012373
TI  - The internal dose of passive smoking at home depends on the size of the dwelling.
AB  - As part of a longitudinal study two urine samples (survey 1 in 1991 and survey 2
      in 1992) were collected from 602 elementary school children to investigate the
      relationship between urinary cotinine excretion (UCE) and the daily consumption
      of cigarettes at home (exposure). Size of the dwelling, educational level, and
      maternal smoking were taken into consideration as additional predictors. The
      history regarding parental smoking habits and confounding variables was
      ascertained by standardized questionnaires completed by the parents. Cotinine was
      measured using gas chromatography selected ion monitoring. UCE was expressed as
      cotinine/creatinine (ng/mg). In children with detectable UCE in survey 1 (35%)
      and in survey 2 (44%) the excretion ranged between 1.5 and 24.7 ng/mg (5-95%) and
      between 1.2 and 25.2 ng/mg, respectively. UCE measurements in both surveys were
      highly correlated (r = 0.65, P = 0.0001), and 59.6% of the UCE in survey 2 can be
      explained in linear regression by the UCE in survey 1. Using multiple linear
      regression, the categorized number of cigarettes reported to be consumed at home
      (20 cigarettes and more: 1991, P = 0.0001; 1992, P = 0.0003) and low educational
      level of the parents (P = 0.011 in 1991, P = 0.04 in 1992) were positively
      associated with UCE, whereas the size of the dwelling turned out to be negatively
      associated with UCE (P = 0.12 in 1991, P = 0.001 in 1992). In small dwellings (<
      or = 80 m2) the effect of exposure on UCE was much more pronounced. In
      conclusion, a single UCE measurement provides information which is widely stable
      within a yearly interval and is related to passive smoke history as well as to
      socio-economic status and the size of the dwelling. The latter variable should be
      considered as an effect modifier of exposure on internal dose and should be taken
      into account in future studies on passive smoke exposure.

PMID- 9012374
TI  - Environmental arsenic exposure of children around a former copper smelter site.
AB  - Arsenic residues in the communities surrounding former smelters remain a public
      health concern, especially for infants and children. To evaluate environmental
      exposure among these children, a population-based cross-sectional study was
      conducted in the vicinity of a former copper smelter in Anaconda, Montana. A
      total of 414 children less than 72 months old were recruited. First morning
      voided urine samples and environmental samples were collected for arsenic
      measurements. The geometric mean of speciated urinary arsenic was 8.6
      microg/liter (GSD = 1.7, N = 289). Average arsenic levels of different types of
      soil ranged from 121 to 236 microg/g and were significantly related to proximity
      and wind direction to the smelter site. The same significant relationship was
      observed for interior dust arsenic. Speciated urinary arsenic was found to be
      significantly related to soil arsenic in bare areas in residential yards (P <
      0.0005). In general, elevated excretion of arsenic was demonstrable and warranted
      parents' attention to reduce exposure of their children to environmental arsenic.

PMID- 9012375
TI  - Measurement error and its impact on the estimated relationship between dust lead
      and children's blood lead: Members of the Rochester Lead-in-Dust Study Group.
AB  - OBJECTIVE: Lead-contaminated house dust is a major contributor to lead intake
      among urban children, but the reliabilities of various dust lead measurement
      methods and their impact on the estimated correlations between dust lead and
      children's blood lead levels are unknown. METHODS: Repeated field measurements of
      lead-contaminated dust from children's homes were taken from 16 housing units
      using five dust lead measurement methods. Estimates of measurement error were
      used to obtain reliability ratios for the dust lead measurements, which were then
      used to correct estimated correlations between lead-contaminated dust and
      children's blood lead. RESULTS: Reliability varied over methods and surface types
      (from 0.0 to 0.8), but wipe loading and the BRM vacuum loading methods generally
      had greater reliability. Technician effects, inadvertent field exposure to lead,
      contamination of collection equipment, and laboratory instrument error were found
      to contribute little to total measurement error. Corrected correlations between
      blood lead and wipe loading measurements were 7 to 104% higher than uncorrected
      correlations. The multiple R2 and partial R2 for a wipe composite measurement in
      a multivariate regression model increased from 0.43 to 0.64 and from 0.053 to
      0.26, respectively, after correction for measurement error bias. CONCLUSIONS:
      Variation in lead deposition within small areas and variations in collection
      inherent to the devices are major contributors to measurement error. Measurement
      error causes dramatic underestimation of correlation between lead-contaminated
      house dust and children's blood lead.

PMID- 9012376
TI  - Three-dimensional DNA image cytometry by confocal scanning laser microscopy in
      thick tissue blocks of prostatic lesions.
AB  - DNA ploidy provides important information for the evaluation of the prognosis of
      prostate cancer. For the purpose of DNA cytometry and nuclear measurements, we
      developed an image processing system for the acquisition and processing of three
      dimensional (3D) images based on confocal scanning laser microscopy (CSLM). The
      advantage of the CSLM is the preservation of the tissue architecture and the
      possibility of multilabeling. It is possible to determine both individual nuclear
      features and cellular features and the degree of the spatial heterogeneity of
      several markers. Special attention was paid to the development of the automatic
      method for the 3D segmentation of cell nuclei. Thick tissue slides (100 microm),
      stained for DNA with chromomycin A3, from 4 patients (with benign hyperplasia,
      prostatic intraepithelial neoplasia (PIN), and well-and poorly-differentiated
      adenocarcinoma of the prostate), were studied in order to test the practicability
      of the developed methodology. DNA histograms showed a single peak in the diploid
      range for the hyperplasia and PIN cases. For the case of well-differentiated
      carcinoma, 2 peaks were observed, 1 in the diploid range and I in the tetraploid
      range. The case of poorly-differentiated carcinoma was characterized by an
      aneuploid distribution. For the cases of PIN and carcinomas, we observed a
      considerable variation of the volume of nuclei.

PMID- 9012377
TI  - Evaluation of cell morphology by video recording and computer-assisted image
      analysis.
AB  - The aim of this study was to evaluate the effects of various cell culture
      conditions on cell morphology. Cell morphology was estimated by means of video
      recording and computer-assisted image analysis. Cell contours from the stored
      images of either live cells or fixed and stained cells were determined
      automatically, and cellular area, form factor, and average cell brightness were
      calculated. Using the mouse fibroblastoid L 929 cell line (L-cells) and the rat
      glioma BT4C cell line, it was found that a number of methodological parameters
      strongly affected cell morphology. These included confluency of cells before
      dissociation, dissociation procedure, cell seeding density, cultivation time, and
      culture substratum. The substratum, particularly collagen type I and fibronectin,
      profoundly affected cell morphology. Using drugs affecting cytoskeletal
      organization or cell substratum interactions, it was shown that average cell
      brightness was a valuable parameter for estimation of cellular attachment.
      Cytochalasin D, which impairs actin filaments, caused a dramatic increase in the
      average cell brightness in both cell lines. Nocodazole, which depolymerizes
      microtubules, mainly affected the L-cells, whereas the BT4C-cells were largely
      unaffected, indicating that microtubules were morphological determinants for the
      former cell line but not for the latter. When cells were grown on fibronectin, an
      RGD-peptide only affected L-cell attachment, indicating that BT4C-cells only
      expressed low (if any) amounts of RGD recognizing integrins. The interassay
      precision of the employed procedure depended on culture substratum; the
      coefficients of variation ranged from 7-24%. Lowest variations in area
      determination were found for cells grown on fibronectin. The coefficient of
      variation of form factor determinations was generally around 20%, independent of
      substrata and culture time.

PMID- 9012378
TI  - Methods for automatic multiparameter analysis of fluorescence in situ hybridized
      specimens with a laser scanning cytometer.
AB  - Multiparameter laser scanning cytometry has been applied to the automatic
      counting of probe spots and the simultaneous measurement of cellular DNA for
      fluorescence in situ hybridization (FISH) prepared specimens counterstained with
      propidium iodide. Relatively low resolution imaging, highly variable probe
      fluorescence, spectral overlap of probe with counterstain fluorescence, and
      autofluorescence required the development of an image processing method to detect
      and isolate FISH probe spots. Inability to properly apportion detected probe
      spots because of overlapping probe spot images in the same cell required
      development of a method to eliminate cell data whenever spots in that cell could
      not be reliably isolated. Laser scanning cytometry incorporating these methods to
      determine per cell probe spot count and DNA is demonstrated on tissue cultures
      and peripheral blood cells using different centromeric FISH probes with either
      FITC or Spectrum Green labeling.

PMID- 9012379
TI  - A directional clustering technique for random data classification.
AB  - This paper introduces a new clustering technique for random data classification
      based on an enhanced version of the Voronoi diagram. This technique is optimized
      to deal in the best way possible with data distributions which in their spatial
      representations experience overlap. A mathematical framework is given in view of
      this enhanced analysis and provides insight to key issues involving (a) the use
      of a correction process to complement the traditional Voronoi diagram and (b) the
      introduction of directional vectors in Gaussian and elliptical data distributions
      for enhanced data clustering. The computational requirements of the proposed
      approach are provided, and the computer results involving both randomly generated
      and real-world data prove the soundness of this clustering technique.

PMID- 9012380
TI  - Measurement of apoptosis in heterogenous cell populations.
AB  - The increasing interest in programmed cell death has created the need to measure
      apoptosis in complex cell systems. We have combined the use of fluorescent
      antibodies with the Hoechst 33342/propidium iodide system in order to quantitate
      programmed cell death in fractions of heterogenous cell populations. Here we
      describe the analysis of T-cell apoptosis after ligation of the T-cell antigen
      receptor by superantigen in vitro and ex vivo. This technique can separate cells
      according to seven parameters, fluorescence caused by FITC, PE, allophycocyanin,
      incorporation of Hoechst 33342, PI, forward scatter, and side scatter, and it
      allows determination of elevated Hoechst 33342 uptake in less than 10% of the
      cell population.

PMID- 9012381
TI  - A novel flow cytometric method for quantifying phagocytosis of apoptotic cells.
AB  - Many eukaryotic cell types are capable of specific recognition and phagocytosis
      of apoptotic cells, and there is increasing interest in the mechanisms involved
      in this process. To facilitate analysis of these mechanisms, we designed a novel
      fluorescence-based method to quantify phagocytosis in vitro using endothelial
      cell engulfment of apoptotic cells as a model. The B-cell line WEHI-231 was
      labeled with the fluorophore 5-(&-6)-carboxytetramethyl-rhodamine-succinimidyl
      ester (TAMRA) and then induced to undergo apoptosis by crosslinking cell surface
      immunoglobulin. An endothelial cell line was subsequently allowed to ingest these
      TAMRA-labeled apoptotic lymphocytes. After 24 h, nonbound lymphocytes were
      removed and the mono-layers were dissociated. Any nonphagocytosed lymphocytes
      that remained tightly bound to the endothelial cells were then indirectly
      immunofluorescein labeled for the pan leukocyte-specific marker CD45. Flow
      cytometric analysis of the cells distinguished three endothellal cell
      populations: 1) endothelial cells with surface bound lymphocytes (TAMRA+ CD45+);
      2) endothelial cells containing phagocytosed apoptotic lymphocytes (TAMRA+ CD45
      ); and 3) endothelial cells that were not associated with lymphocytes. The
      identification of these populations was verified by confocal microscopy of sorted
      cells. The method described herein will facilitate detailed studies on phagocytic
      recognition of apoptotic cells and should have broad applications to other
      phagocytic cell systems.

PMID- 9012382
TI  - Nucleic acid specificity of an acridine derivative permits its use for flow
      cytometric analysis of the cell cycle.
AB  - 3-amino-6-methoxy-9-(2-hydroxyethylamine) acridine (AMHA) is an acridine
      derivative, which is easily excited in near ultraviolet and which emits a bright
      green fluorescence. The dye was preferentially incorporated into nucleic
      structures as attested by microscopic and cytometric analyses after RNase and
      DNase treatments. The affinity for RNA seemed low and similar to that observed
      for propidium iodide. AMHA was quickly accumulated in fixed cells, and in
      appropriate concentrations (10-50 microM) was a DNA- and RNA-specific dye. AMHA
      probably exhibits an adenine-thymine specificity, as suggested by its quenching
      after bromodeoxyuridine uptake: the fluorescence quenching was similar to that
      obtained for Hoechst 33258. After cell treatment by RNase and in the presence of
      MgCl2, AMHA staining allowed flow cytometric analysis of the cell-cycle
      distribution. The resulting histograms were similar to those obtained with
      propidium iodide (CV near 3.5%, and similar cell cycle distribution). Thus, AMHA
      is a suitable fluorescent dye for efficient analysis of the cell cycle by flow
      cytometry.

PMID- 9012383
TI  - Three-parameter flow cytometric analysis of rat spermatogenesis.
AB  - Mammalian spermatogenesis is a complex process which is not yet fully understood.
      In this paper we describe the analysis of rat spermatogenesis by means of 3
      parameter flow cytometry. Since the analysis of DNA content only provides
      sufficient information for the identification of 4 cell populations, additional
      parameters were combined with propidium iodide (PI) staining. Immunostaining of
      the intermediate filament vimentin allowed the identification of somatic
      (vimentin positive) and germ (vimentin negative) cells. Utilizing the combination
      of DNA and vimentin staining, we have been able to quantitate the somatic cells
      present in a testicular cell suspension and to analyze somatic and germinal cells
      separately. Furthermore, the addition of mitochondrial staining with the
      fluorochrome nonyl acridine orange (NAO) allowed several cell subpopulations
      within each ploidy group to be distinguished. After 3-color staining and
      subsequent cell sorting, 11 testicular cell subpopulations could be identified:
      somatic cells, and 10 subtypes of germinal cells. The method described in this
      paper represents a valuable tool for the evaluation of spermatogenesis in both
      normal and perturbed situations.

PMID- 9012384
TI  - Rapid assessment of ceftazidime, ciprofloxacin, and gentamicin susceptibility in
      exponentially-growing E. coli cells by means of flow cytometry.
AB  - Exponentially growing E. coli cells were cultivated in the presence of
      ceftazidime, ciprofloxacin, and gentamicin in concentrations ranging from 0.5-8
      minimal inhibitory concentration (MIC), permeabilized by means of cold shock in
      EDTA/azide, and stained with the DNA-specific dye combination of ethidium bromide
      and mithramycin before the fluorescence, light scattering, and cell number were
      measured flow-cytometrically. In order to evaluate the applicability of the cold
      shock procedure, cells were also permeabillized by 70% ethanol. Permeabilization
      by cold shock, which eliminates washing of the cells, reduced the preparation
      time to <5 min. A statistically significant increase in light scattering and
      fluorescence, i.e., cell size and DNA content, could be detected already after 30
      min of ceftazidime and ciprofloxacin exposure, even at sub-MIC concentrations.
      The results obtained with these drugs with cold-shock permeabilization were
      similar to those seen with ethanol fixation. For gentamicin-treated cells,
      however, a majority of the cells lost their fluorescence after cold shock. In
      gentamicin-treated cells fixed in ethanol, there was no consistent effect on
      either light scattering or fluorescence; however, we observed a substantial
      fragmentation and leakage of DNA in such cells. The cell proliferation was
      completely inhibited within 30 min of gentamicin incubation. For all three drugs,
      loss of light scattering and DNA were associated with cellular disintegration,
      i.e., reduced viability. The present results demonstrate that effects of
      ceftazidime, ciprofloxacin, and gentamicin on E. coli can be detected by flow
      cytometry within 1 h from the beginning of drug exposure to the completed
      measurement.

PMID- 9012385
TI  - Trivariate flow cytometric analysis of paraffin-embedded lung cancer specimens:
      application of cytokeratin subtype specific antibodies to distinguish between
      differentiation pathways.
AB  - The aim of the present study was to investigate whether trivariate FCM analysis,
      for the simultaneous detection of two different CK subtypes in combination with
      DNA content, can be applied to paraffin embedded samples of different types of
      non-small cell lung cancer in order to evaluate the cell cycle of individual
      sublines. Single cell suspensions were prepared from 50 microm thick paraffin
      sections of 22 lung carcinomas by pepsin digestion and immunostained with CK
      antibodies which were chosen to distinguish glandular differentiation
      (adenocarcinomas) and squamous differentiation. There was a good correlation
      between the immunocytochemical results of the different CK antibodies in tissue
      sections and in the corresponding single cell suspensions. Gating for CK
      positivity revealed a higher S-phase fraction as compared to the ungated cell
      population. The tumor cells in adenocarcinoma cases were specifically recognized
      by CK7 antibodies, while well-differentiated squamous cell carcinomas were
      specifically stained for CK14 and/or CK17. In poorly differentiated squamous cell
      carcinomas simultaneous expression of CK7 and CK17 was detected in a
      subpopulation of the tumor cells, next to cells positive for CK7 or CK17 alone.
      The trivariate FCM analysis allowed the separate estimation of ploidy status and
      cell cycle parameters in the three different cell populations of these,
      apparently (phenotypically) heterogeneous, malignancies.

PMID- 9012386
TI  - Comparative scoring by visual and image analysis of cells in human solid tumors
      labeled for proliferation markers.
AB  - This study determined the validity of an image analysis program developed to
      score individual cells in human solid tumors labeled by proliferating cell
      nuclear antigen (PCNA) or bromodeoxyuridine (BrdUrd). The program used nuclear
      size, grey level, and perimeter convexity to identify cells, and evaluated
      labeling by the fraction of nuclear area displaying positive immunostaining
      (MPB). Total cell number (TC) and BrdUrd or PCNA labeling index (LI) were
      evaluated in 142 images using visual (TCvisual, LIvisual) and image analysis
      (TC(IA), LI(IA)). Without the perimeter convexity criterion, image analysis
      resulted in a) TC(IA) equal to TCvisual in spite of the presence of various non
      cellular objects and b) significant correlations between LI(IA) and LIvisual for
      PCNA and BrdUrd, although for these markers the LI(IA) were 4 and 6% lower than
      their respective LIvisual. Both visual and image analyses yielded significant
      inter-investigator variation among three investigators (coefficient of variation
      between 8.2 and 47.5%) and significant intra-investigator, inter-day variation
      (coefficients of variation between 3.8 and 51.8%). We conclude that image
      analysis using size, grey level and MPB is a valid alternative to visual scoring
      of PCNA and BrdUrd LI in individual cells.

PMID- 9012387
TI  - Variability in tissue characterization of atherosclerotic plaque by intravascular
      ultrasound: a comparison of four intravascular ultrasound systems.
AB  - Different intravascular ultrasound (IVUS) systems vary in their image
      presentation. The purpose of this study was to compare four IVUS systems in vitro
      to determine the accuracy of tissue characterization of atherosclerotic plaque
      compared with histology. Ninety-eight plaque segments from 23 formalin-fixed
      human iliac arteries were imaged in saline at room temperature with four
      different IVUS systems. To assess the accuracy of IVUS in describing plaque,
      three types of analysis were performed: (1) the ability to identify the presence
      and extent of lumen or plaque boundary; (2) sensitivity, specificity, and
      interobserver variability of IVUS in qualitatively identifying plaque components
      compared with histology; and (3) quantification of calcification. The synthetic
      aperture device had a lower sensitivity in identifying lumen and plaque
      boundaries (87%, 38% respectively) compared with other machines (96%-100%, 95%
      100%). All three mechanically rotating systems had fair to good sensitivities for
      identifying calcification (57%-73%) or lipid filled areas (50%-83%). The
      sensitivity of discriminating fibrous tissue from fatty areas was low (39%-52%).
      The synthetic aperture system had a significantly lower sensitivity for
      identifying all three tissue types (4%-21%). There was significant interobserver
      variability (kappa value = 0.47-0.68) as well as machine to machine variability
      (kappa value = 0.52) for tissue characterization. Calcified areas were
      underestimated by System 1 (p < .05) and System 4 (p < .01) because of weaker
      echo reflections or poor image quality. There are significant differences in
      image representation among these four IVUS systems in the diagnosis of tissue
      components of complex atherosclerotic plaque. These variabilities should be
      considered when interpreting studies performed with different machines.

PMID- 9012388
TI  - Variability of a three-layered appearance in intravascular ultrasound coronary
      images: a comparison of morphometric measurements with four intravascular
      ultrasound systems.
AB  - The purpose of the study was to compare four intravascular ultrasound (IVUS)
      machines in vitro for their image representation of coronary arterial walls.
      There has been considerable variability among reported studies on the accuracy of
      morphometric measurements of coronary arteries by IVUS. This variability may be
      caused in part by the difference in the IVUS system used. A total of 24 formalin
      fixed coronary arteries were imaged in saline at 37 degrees with four different
      IVUS systems. The images were interpreted independently and compared with
      histology. Each system had benefits and limitations: System 1 overestimated the
      lumen area and had difficulty in identifying the media; System 2 underestimated
      the media area, but had a lower positive bias for lumen area; System 3
      overestimated the lumen area but more clearly identified tissue characteristics
      such as internal elastic membrane and the echolucent media zone which improved
      the likelihood of observing a three-layer appearance; and System 4 showed less
      distinct separation of the arterial components and had poor correlations with
      histology for media measurements. The ability to make accurate morphometric
      measurements from IVUS images depends on the clarity of the separation of plaque
      and media. Among the four systems studied, there is significant variability in
      the appearance of the ultrasound images and the accuracy of morphometric
      measurements. These system differences should be considered when comparing IVUS
      studies performed by different groups.

PMID- 9012389
TI  - Contrast-enhanced radiographic computed tomographic findings in patients with
      straight back syndrome.
AB  - Straight back syndrome (SBS) is usually diagnosed by physical and chest
      radiographic findings. Radiographic computed tomographic (CT) findings are very
      useful for the diagnosis and the evaluation of its severity. The purpose is to
      evaluate the relationship between chest X-ray film and CT findings. SUBJECTS: We
      evaluated 26 patients (SBS group) and 11 normal subjects (control group). SBS
      group consisted of 15 patients without structural heart disease (group I) and 11
      patients with other heart disease (group II). METHODS: (1) On the chest X-ray
      film, antero-posterior diameter (APD) of the thorax, transthoracic diameter
      (TTD), and APD/TTD ratio were measured. (2) On the CT image, three parameters
      were calculated; APD of the left atrium (LA diameter), APD/transverse diameter
      ratio of the heart (flattening ratio) and left side shift ratio of the heart
      (shifting ratio). (3) CT parameters were compared with APD/TTD ratio in patients
      and control group. RESULTS: (1) APD/TTD ratio was smaller in group I and II than
      control group (30.0 +/- 5.4, 30.5 +/- 4.0 v 44.6 +/- 2.7%, p < .001). (2) LA
      diameter was smaller in group I and II than control group (23.2 +/- 4.1, 26.0 +/-
      8.6 v 30.0 +/- 6.5 mm, p < .01). Flattening ratio was also smaller in group I and
      II than control group (59.2 +/- 9.4, 61.8 +/- 8.6 v 75.4 +/- 13.2%, p < .01).
      Shifting ratio was greater in group I and II than control group (10.9 +/- 5.0,
      11.9 +/- 4.5 v 8.4 +/- 4.0%, p < .01). (3) APD/TTD ratio correlated with LA
      diameter (r = .39, p < .05) and flattening ratio (r = .53, p < .001). APD/TTD
      ratio did not correlate with shifting ratio (r = -.27, NS). CONCLUSIONS: APD/TTD
      ratio correlated with LA diameter and flattening ratio rather than shifting
      ratio. LA diameter and flattening ratio on the CT image were more useful for
      evaluating the severity.

PMID- 9012390
TI  - Comparison of 10, 20, and 40 level electron beam computed tomography studies for
      coronary calcium.
AB  - There are increasing data to support the use of the electron beam computed
      tomography (EBCT) scanner for early detection of coronary artery disease (CAD). A
      negative scan essentially rules out significant disease. How many EBCT 3 mm
      contiguous slices are needed to cover the coronary circulation? To answer this
      question, 104 consecutive patients referred for EBCT scan for evaluation of
      coronary artery calcium (CAC) were asked to participate. The sensitivity and
      negative predictive value (NPV) of calcium scores for the first 10 slices and
      first 20 slices, the second 20 slices, and the total scan were recorded. Scores
      greater than one were regarded as positive. The number of levels required to
      cover the entire heart was also recorded. Fifty-nine patients (56.7%) had a
      positive calcium score for the total scan. Of these, 53 were positive for the
      first 10 slices (sensitivity = 89.8%, NPV 88.2%), and 57 were positive for the
      first 20 slices (sensitivity = 96.6%, NPV 95.7%). The median number of levels
      required to cover the entire heart was 34, and 97.2% of cases were covered in 40
      or fewer levels. The use of 20 slices for purposes of detecting CAC is a
      reasonable choice for the C-100 scanners, because this would be accomplished in a
      breath hold. When the first slice starts at the base of the right pulmonary
      artery, all patients with CAC were identified. The C-150 scanner with the ability
      to scan on each heartbeat would increase sensitivity and NPV by acquiring 30 to
      40 slices in a single breath hold.

PMID- 9012391
TI  - Variation of heart rate and electrocardiograph trigger interval during ultrafast
      computed tomography.
AB  - OBJECTIVES: Electrocardiographic (ECG) trigger records obtained during cardiac
      ultrafast computed tomography (UFCT) scanning were analyzed to estimate the
      variability in heart rate and ECG trigger interval to develop a protocol that
      would allow the development of better ECG triggering software. METHODS: One
      hundred-eighteen patients underwent cardiac UFCT imaging for diagnostic purposes.
      All subjects were divided into three groups according to the heart rate and ECG
      trigger condition. Thirty slices were obtained in the high-resolution volume mode
      for each patient. RESULTS: A decrease in heart rate and ECG trigger interval was
      found during image acquisition of the first four slices in all three groups. The
      nadir of the heart rate occurred during acquisition of the 4th slice, 5.3, 3.5,
      and 5.6 beats per minute less than the initial heart rate in groups 1, 2, and 3
      respectively, with a 6.9%, 2.8%, and 5.0% shorter ECG trigger interval (p < .001,
      p = .08, p < .05, respectively). From the 4th to the 30th slices, heart rate and
      ECG trigger interval progressively increased, but less variability was found in
      the last 20 slices in all three groups. CONCLUSIONS: Significant variation in
      heart rate and ECG trigger interval was seen during 30-level cardiac UFCT
      imaging, especially during image acquisition of the first four slices
      (approximately 1-6 seconds after breatholding). This can result in scanning
      during the suboptimal phase of the cardiac cycle by the current UFCT triggering
      software. A delay in the initiation of scanning to approximately 6 to 10 seconds
      after breatholding would result in imaging during a time when the heart rate is
      relatively stable, and a smaller variability in ECG trigger interval occurs.
      Recalculation of the required delay before each heart beat may improve the
      precision of ECG triggering.

PMID- 9012392
TI  - Evaluation of reference systems for quantitative wall motion analysis from three
      dimensional endocardial surface reconstruction: an echocardiographic study in
      subjects with and without myocardial infarction.
AB  - Six relevant computer-implemented reference systems for three-dimensional
      quantitative assessment of left ventricular wall motion abnormalities were
      compared with visual wall motion analysis of two-dimensional images. Endocardial
      borders were traced in three apical echocardiographic views at end-diastole and
      end-systole in 10 patients with myocardial infarction and 5 healthy subjects, and
      three-dimensional reconstruction of endocardial surfaces was performed. End
      diastolic and end-systolic surfaces were aligned in a common axis system
      depending on the reference system, and systolic wall motion was assessed at 1,024
      points on the endocardial surface. The localization of abnormal wall motion was
      displayed in bull's-eye maps, and the area was determined as a percentage of
      total endocardial area. For each reference system, the segmental concordance
      between three-dimensional computerized and visual assessment was determined. The
      best agreement between computerized and visual analysis was obtained with a
      reference system based on wall motion towards the major ventricular axis, whereas
      the poorest result was obtained using the center of left ventricular cavity as
      reference. Correlation between the estimated area of wall motion abnormality and
      visually determined wall motion score index was best using the aligned center of
      mitral valve plane as reference (r = .92).

PMID- 9012393
TI  - Doppler echocardiographic assessment of the new ATS medical prosthetic valve in
      the aortic position.
AB  - Advancing The Standard (ATS) Medical (ATS Medical Inc., Minneapolis, MN) is a new
      mechanical bileaflet valve, composed of pyrolitic carbon. The aim of this study
      was to define in a blinded manner the Doppler echocardiographic characteristics
      of normally functioning ATS Medical prostheses with respect to their size. Forty
      consecutive patients (29 men, mean age 58 +/- 13 years), clinically stable, and
      without evidence of valve dysfunction, were studied from 1993 to 1995. Doppler
      echocardiography was performed at least 3 months after valve replacement with ATS
      Medical valves (5 n degrees 21, 8 n degrees 23, 12 n degrees 25, 10 n degrees 27,
      5 n degrees 29). Maximum and mean transprosthetic pressure gradients were
      calculated by the simplified Bernoulli equation. Functional valve surface area
      was assessed by the continuity equation using the external diameter of the
      prostheses to calculate the subaortic surface area. The Doppler velocity index
      was obtained by the ratio of subaortic and transaortic velocities and the
      performance index was calculated dividing the effective orifice area by the
      actual orifice area. For the most commonly used aortic valve (25 mm), the maximum
      pressure gradient was 17 +/- 8 mmHg, the mean gradient 11 +/- 4 mmHg, the
      functional surface area 2.2 +/- 0.4 cm2, the Doppler velocity index 0.44 +/-
      0.07, and the performance index 0.68 +/- 0.11. This study provides the normal
      range for Doppler hemodynamic characteristics of the various sizes of the ATS
      valve.

PMID- 9012394
TI  - Effect of left atrial size on recurrence of atrial fibrillation after electrical
      cardioversion: atrial dimension versus volume.
AB  - There are conflicting reports on the relationship between left atrial dimension
      (LAD) determined by echo-cardiography and the incidence of atrial fibrillation
      (AF) recurrence after electrical cardioversion (EC). We hypothesized that left
      atrial volume (LAV) by echocardiography might better differentiate patients who
      will have recurrence of AF after EC. METHODS: Forty-one patients having EC for AF
      were prospectively studied by echocardiography. LAD was measured by American
      Society of Echocardiography guidelines as the anterior-posterior dimension in the
      parasternal view. LAV was measured by Simpson's method using an off-line analysis
      system and reported as the average of values from the apical four-chamber and two
      chamber views. RESULTS: (Data are mean +/- SEM): Patient follow-up was 15 +/- 10
      months. No cutoff value of LAV predicted AF recurrence, but all three patients
      with LAD greater than 65 mm had AF recurrence. Compared with patients maintaining
      normal sinus rhythm (NSR) (N = 18), the AF group (N = 23) had a lower percentage
      of antiarrhythmic drug use, especially type IA agents (p < .02). Patients who
      stayed in NSR tended to have shorter AF duration before EC (16 +/- 15 v 63 +/-
      122 weeks, p = .08) but did not differ in age (53 +/- 27 v 58 +/- 23 years), LAD
      (51.1 +/- 7.7 v 54.2 +/- 9.4 mm) or LAV (85.1 +/- 24.3 v 95.1 +/- 33.3 mL).
      CONCLUSIONS: (1) LAV by echocardiography does not improve identification of
      patients at risk for recurrence of AF after EC, (2) patients with LAD up to 65 mm
      may maintain NSR after EC, (3) LAD greater than 65 mm is associated with AF
      recurrence, and (4) use of antiarrhythmic drugs and the duration of AF before EC
      may be better predictors of maintenance of NSR than echocardiographic measures of
      left atrial parameters.

PMID- 9012395
TI  - Transesophageal echocardiography during removal of central venous catheter
      associated with thrombus in superior vena cava.
AB  - Thrombosis of upper extremity veins and superior vena cava (SVC) can occur in
      patients with indwelling central venous catheters. Contrary to earlier reports,
      pulmonary embolism (PE) can result from these thrombi, especially when they are
      attached to catheters (sleeve thrombi) in contrast to venous wall (mural
      thrombi). Removal of catheters may be required when sepsis occurs or to reduce
      risk of sepsis when lines have been left in for several days. We describe two
      patients with thrombi in SVC related to central venous catheters in whom
      transesophageal echocardiography (TEE) was performed during catheter removal to
      monitor for thrombus dislodgement. TEE may have a role in showing thrombus
      dislodgement and embolization during removal of venous catheters complicated by
      SVC thrombi. Direct visualization of thrombus dislodgement may aid in early
      diagnosis of PE because signs and symptoms of PE are often missed or mistaken for
      underlying cardiopulmonary disease. TEE may also play a role in implementing
      appropriate treatment in patients with PE who show right ventricular strain.

PMID- 9012396
TI  - 1996 William Allan Award Address. Algorithms and inferences: the challenge of
      multifactorial diseases.

PMID- 9012397
TI  - 1996 ASHG Award for excellence in education. Remarks on receiving the ASHG award
      for education.

PMID- 9012398
TI  - Polymorphisms in drug-metabolizing enzymes: what is their clinical relevance and
      why do they exist?

PMID- 9012399
TI  - Molecular genetics of the glaucomas: mapping of the first five "GLC" loci.

PMID- 9012400
TI  - Gene regulation by mRNA editing.

PMID- 9012401
TI  - Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and
      phenotypic consequences.
AB  - Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity
      ranges from complete deficiency to ultrafast metabolism, depending on at least 16
      different known alleles. Their frequencies were determined in 589 unrelated
      German volunteers and correlated with enzyme activity measured by phenotyping
      with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from
      a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the
      CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The
      alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced
      activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324,
      .018, and .015, respectively. By use of novel PCR tests for discrimination,
      CYP2D6 gene duplication alleles were found with frequencies of .005 (*1x2), .013
      (*2x2), and .001 (*4x2). Frequencies of alleles with complete deficiency (poor
      metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001
      (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were
      not found. All 41 PMs (7.0%) in this sample were explained by five mutations
      detected by four PCR-RFLP tests, which may suffice, together with the gene
      duplication test, for clinical prediction of CYP2D6 capacity. Three novel
      variants of known CYP2D6 alleles were discovered: *1C (T1957C), *2B (additional
      C2558T), and *4E (additional C2938T). Analysis of variance showed significant
      differences in enzymatic activity measured by the dextromethorphan metabolic
      ratio (MR) between carriers of EM/PM (mean MR = .006) and IM/PM (mean MR = .014)
      alleles and between carriers of one (mean MR = .009) and two (mean MR = .003)
      functional alleles. The results of this study provide a solid basis for
      prediction of CYP2D6 capacity, as required in drug research and routine drug
      treatment.

PMID- 9012402
TI  - Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.
AB  - Glaucoma is the third-leading cause of blindness in the world, affecting >13.5
      million people. Adult-onset primary open-angle glaucoma (POAG) is the most common
      form of glaucoma in the United States. We present a family in which adult-onset
      POAG is inherited as an autosomal dominant trait. Twelve affected family members
      were identified from 44 at-risk individuals. The disease-causing gene was mapped
      to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total
      inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the
      first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol
      GLC1C.

PMID- 9012403
TI  - A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors.
AB  - Neurofibromatosis type I (NF1) is a common disorder that predisposes to neoplasia
      in tissues derived from the embryonic neural crest. The NF1 gene encodes a tumor
      suppressor that most likely acts through the interaction of its GTPase-activating
      protein (GAP)-related domain (GRD) with the product of the ras protooncogene. We
      have previously identified a site in the NF1 mRNA, within the first half of the
      NF1 GRD, which undergoes base-modification editing. Editing at that site changes
      a C to a U, thereby introducing an in-frame stop codon. NF1 RNA editing has been
      detected in all cell types studied, to date. In order to investigate the role
      played by editing in NF1 tumorigenesis, we analyzed RNA from 19 NF1 and 4 non-NF1
      tumors. We observed varying levels of NF1 mRNA editing in different tumors, with
      a higher range of editing levels in more malignant tumors (e.g.,
      neurofibrosarcomas) compared to benign tumors (cutaneous neurofibromas).
      Plexiform neurofibromas have an intermediate range of levels of NF1 mRNA editing.
      We also compared tumor and nontumor tissues from several NF1 individuals, to
      determine the extent of variability present in the constitutional levels of NF1
      mRNA editing and to determine whether higher levels are present in tumors. The
      constitutional levels of NF1 mRNA editing varied slightly but were consistent
      with the levels observed in non-NF1 individuals. In every case, there was a
      greater level of NF1 mRNA editing in the tumor than in the nontumor tissue from
      the same patient. These results suggest that inappropriately high levels of NF1
      mRNA editing does play a role in NF1 tumorigenesis and that editing may result in
      the functional equivalent of biallelic inactivation of the NF1 tumor suppressor.

PMID- 9012404
TI  - Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population.
AB  - A population-based series of 54 male breast cancer cases from Southern California
      were analyzed for germ-line mutations in the inherited breast/ovarian cancer
      genes, BRCA1 and BRCA2. Nine (17%) of the patients had a family history of breast
      and/or ovarian cancer in at least one first-degree relative. A further seven
      (13%) of the patients reported breast/ovarian cancer in at least one second
      degree relative and in no first-degree relatives. No germ-line BRCA1 mutations
      were found. Two male breast cancer patients (4% of the total) were found to carry
      novel truncating mutations in the BRCA2 gene. Only one of the two male breast
      cancer patients carrying a BRCA2 mutation had a family history of cancer, with
      one case of ovarian cancer in a first-degree relative. The remaining eight cases
      (89%) of male breast cancer with a family history of breast/ovarian cancer in
      first-degree relatives remain unaccounted for by mutations in either the BRCA1
      gene or the BRCA2 gene.

PMID- 9012405
TI  - A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with
      trichothiodystrophy.
AB  - Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized
      by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual
      development, and ichthyosis. Photosensitivity has been reported in approximately
      50% of the cases, but no skin cancer is associated with TTD. Virtually all
      photosensitive TTD patients have a deficiency in the nucleotide excision repair
      (NER) of UV-induced DNA damage that is indistinguishable from that of xeroderma
      pigmentosum (XP) complementation group D (XP-D) patients. DNA repair defects in
      XP-D are associated with two additional, quite different diseases; XP, a sun
      sensitive and cancer-prone repair disorder, and Cockayne syndrome (CS), a
      photosensitive condition characterized by physical and mental retardation and
      wizened facial appearance. One photosensitive TTD case constitutes a new repair
      deficient complementation group, TTD-A. Remarkably, both TTD-A and XP-D defects
      are associated with subunits of TFIIH, a basal transcription factor with a second
      function in DNA repair. Thus, mutations in TFIIH components may, on top of a
      repair defect, also cause transcriptional insufficiency, which may explain part
      of the non-XP clinical features of TTD. Besides XPD and TTDA, the XPB gene
      product is also part of TFIIH. To date, three patients with the remarkable
      conjunction of XP and CS but not TTD have been assigned to XP complementation
      group B (XP-B). Here we present the characterization of the NER defect in two
      mild TTD patients (TTD6VI and TTD4VI) and confirm the assignment to X-PB. The
      causative mutation was found to be a single base substitution resulting in a
      missense mutation (T119P) in a region of the XPB protein completely conserved in
      yeast, Drosophila, mouse, and man. These findings define a third TTD
      complementation group, extend the clinical heterogeneity associated with XP-B,
      stress the exclusive relationship between TTD and mutations in subunits of
      repair/transcription factor TFIIH, and strongly support the concept of
      "transcription syndromes."

PMID- 9012406
TI  - Mutations in the consensus helicase domains of the Werner syndrome gene. Werner's
      Syndrome Collaborative Group.
AB  - Werner syndrome (WS) is an autosomal recessive disease with a complex phenotype
      that is suggestive of accelerated aging. WS is caused by mutations in a gene,
      WRN, that encodes a predicted 1,432-amino-acid protein with homology to DNA and
      RNA helicases. Previous work identified four WS mutations in the 3' end of the
      gene, which resulted in predicted truncated protein products of 1,060-1,247 amino
      acids but did not disrupt the helicase domain region (amino acids 569-859). Here,
      additional WS subjects were screened for mutations, and the intron-exon structure
      of the gene was determined. A total of 35 exons were defined, with the coding
      sequences beginning in the second exon. Five new WS mutations were identified:
      two nonsense mutations at codons 369 and 889; a mutation at a splice-junction
      site, resulting in a predicted truncated protein of 760 amino acids; a 1-bp
      deletion causing a frameshift; and a predicted truncated protein of 391 amino
      acids. Another deletion is >15 kb of genomic DNA, including exons 19-23; the
      predicted protein is 1,186 amino acids long. Four of these new mutations either
      partially disrupt the helicase domain region or result in predicted protein
      products completely missing the helicase region. These results confirm that
      mutations in the WRN gene are responsible for WS. Also, the location of the
      mutations indicates that the presence or absence of the helicase domain does not
      influence the WS phenotype and suggests that WS is the result of complete loss of
      function of the WRN gene product.

PMID- 9012407
TI  - Identification of mutations in cystatin B, the gene responsible for the
      Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1).
AB  - Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder,
      characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures.
      The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The
      gene for the proteinase inhibitor cystatin B was recently localized in the EPM1
      critical region, and mutations were identified in two EPM1 families. We have
      identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1
      families from northern Africa and Europe. The 426G-->C change in exon 1 results
      in a Gly4Arg substitution and is the first missense mutation described that is
      associated with EPM1. Molecular modeling predicts that this substitution severely
      affects the contact of cystatin B with papain. Mutations in the invariant AG
      dinucleotides of the acceptor sites of introns 1 and 2 probably result in
      abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift
      and truncates the protein. Therefore, these four mutations are all predicted to
      impair the production of functional protein. These mutations were found in 7 of
      the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in
      heterozygosity in the others. The remaining two sequence changes, 431G-->T and
      2575A-->G, probably represent polymorphic variants. In addition, a tandem repeat
      in the 5' UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It
      is peculiar that in the majority of patients no mutations exist within the exons
      and splice sites of the cystatin B gene.

PMID- 9012408
TI  - Cloning of the human type XVII collagen gene (COL17A1), and detection of novel
      mutations in generalized atrophic benign epidermolysis bullosa.
AB  - Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal variant
      of junctional epidermolysis bullosa (JEB). Previous findings have suggested that
      type XVII collagen is the candidate gene for mutations in this disease. We now
      have cloned the entire human type XVII collagen gene (COL17A1) and have
      elucidated its intron-exon organization. The gene comprises 56 distinct exons,
      which span approximately 52 kb of the genome, on the long arm of chromosome 10.
      It encodes a polypeptide, the alpha1(XVII) chain, consisting of an intracellular
      globular domain, a transmembrane segment, and an extracellular domain that
      contains 15 separate collagenous subdomains, the largest consisting of 242 amino
      acids. We also have developed a strategy to identify mutations in COL17A1 by use
      of PCR amplification of genomic DNA, using primers placed on the flanking
      introns. The PCR products are scanned for sequence variants by heteroduplex
      analysis using conformation-sensitive gel electrophoresis and then are subjected
      to direct automated sequencing. We have identified several intragenic
      polymorphisms in COL17A1, as well as mutations, in both alleles, in two Finnish
      families with GABEB. The probands in both families showed negative
      immunofluorescence staining with an anti-type XVII collagen antibody. In one
      family, the proband was homozygous for a 5-bp deletion, 2944del5, which resulted
      in frameshift and a premature termination codon of translation. The proband in
      the other family was a compound heterozygote, with one allele containing the
      2944del5 mutation and the other containing a nonsense mutation, Q1023X. These
      results expand the mutation database in different variants of JEB, and they
      attest to the functional importance of type XVII collagen as a transmembrane
      component of the hemidesmosomes at the dermal/epidermal junction.

PMID- 9012409
TI  - Molecular basis for Duarte and Los Angeles variant galactosemia.
AB  - Human orythrocytes that are homozygous for the Duarte enzyme variant of
      galactosemia (D/D) have a characteristic isoform on isoelectric focusing and 50%
      reduction in galactose-1-phosphate uridyltransferase (GALT) enzyme activity. The
      Duarte biochemical phenotype has a molecular genotype of N314D/N314D. The
      characteristic Duarte isoform is also associated with a variant called the "Los
      Angeles (LA) phenotype," which has increased GALT enzyme activity. We evaluated
      GALT enzyme activity and screened the GALT genes of 145 patients with one or more
      N314D-containing alleles. We found seven with the LA biochemical phenotype, and
      all had a 1721C-->T transition in exon 7 in cis with the N314D missense mutation.
      The 1721C-->T transition is a neutral polymorphism for leucine at amino acid 218
      (L218L). In pedigree analyses, this 1721C-->T transition segregated with the LA
      phenotype of increased GALT activity in three different biochemical phenotypes
      (LA/N, LA/G, and LA/D). To determine the mechanism for increased activity of the
      LA variant, we compared GALT mRNA, protein abundance, and enzyme thermal
      stability in lymphoblast cell lines of D and LA phenotypes with comparable
      genotypes. GALT protein abundance was increased in LA compared to D alleles, but
      mRNA was similar among all genotypes. When LA/D and D/D GALT biochemical
      phenotypes were compared to N/N GALT phenotypes, both had 50%, as compared to
      21%, reduction in GALT activity in the wild type (N/N) after exposure at
      identical initial enzyme activity to 50 degrees C for 15 min. We conclude that
      the codon change N314D in cis with the base-pair transition 1721C-->T produces
      the LA variant of galactosemia and that this nucleotide change increases GALT
      activity by increasing GALT protein abundance without increasing transcription or
      decreasing thermal lability. A favorable codon bias for the mutated codon with
      consequently increased translation rates is postulated as the mechanism.

PMID- 9012410
TI  - A new mtDNA mutation showing accumulation with time and restriction to skeletal
      muscle.
AB  - We have identified a new mutation in mtDNA, involving tRNALeu(CUN) in a patient
      manifesting an isolated skeletal myopathy. This heteroplasmic A-->G transition at
      position 12320 affects the T psi C loop at a conserved site and was not found in
      120 controls. Analysis of cultured fibroblasts, white blood cells/platelets, and
      skeletal muscle showed that only skeletal muscle contained the mutation and that
      only this tissue demonstrated a biochemical defect of respiratory-chain activity.
      In a series of four muscle-biopsy specimens taken over a 12-year period, there
      was a gradual increase, from 70% to 90%, in the overall level of mutation, as
      well as a marked clinical deterioration. Single-fiber PCR confirmed that the
      proportion of mutant mtDNA was highest in cytochrome c oxidase-negative fibers.
      This study, which reports a mutation involving tRNALeu(CUN), demonstrates clearly
      that mtDNA point mutations can accumulate over time and may be restricted in
      their tissue distribution. Furthermore, clinical deterioration seemed to follow
      the increase in the level of mutation, although, interestingly, the appearance of
      fibers deficient in respiratory-chain activity showed a lag period.

PMID- 9012411
TI  - Clustering of Caucasian Leber hereditary optic neuropathy patients containing the
      11778 or 14484 mutations on an mtDNA lineage.
AB  - Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA
      mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and
      14484 are specific for LHON and account for 90% of worldwide cases and are thus
      designated as "primary" LHON mutations. Fifteen other "secondary" LHON mtDNA
      mutations have been identified, but their pathogenicity is unclear. mtDNA
      haplotype and phylogenetic analysis of the primary LHON mutations in North
      American Caucasian patients and controls has shown that, unlike the 3460 and
      11778 mutations, which are distributed throughout the European-derived
      (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be
      associated with European mtDNA haplotype J. To investigate this apparent
      clustering, we performed chi2-based statistical analyses to compare the
      distribution of LHON patients on the Caucasian phylogenetic tree. Our results
      indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not
      distributed on the phylogeny in proportion to the frequencies of the major
      Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next
      shown to occur on the haplogroup J background more frequently that expected,
      consistent with the observation that approximately 75% of worldwide 14484
      positive LHON patients occur in association with haplogroup J. The 11778 mutation
      also exhibited a moderate clustering on haplogroup J. These observations were
      supported by statistical analysis using all available mutation frequencies
      reported in the literature. This paper thus illustrates the potential importance
      of genetic background in certain mtDNA-based diseases, speculates on a pathogenic
      role for a subset of LHON secondary mutations and their interaction with primary
      mutations, and provides support for a polygenic model for LHON expression in some
      cases.

PMID- 9012412
TI  - Sequence variation at the phenylalanine hydroxylase gene in the British Isles.
AB  - Using mutation and haplotype analysis, we have examined the phenylalanine
      hydroxylase gene in the phenylketonuria populations of four geographical areas of
      the British Isles: the west of Scotland, southern Wales, and southwestern and
      southeastern England. The enormous genetic diversity of this locus within the
      British Isles is demonstrated in the large number of different mutations
      characterized and in the variety of genetic backgrounds on which individual
      mutations are found. Allele frequencies of the more common mutations exhibited
      significant nonrandom distribution in a north/south differentiation. Differences
      between the west of Scotland and southwestern England may be related to different
      events in the recent and past histories of their respective populations.
      Similarities between southern Wales and southeastern England are likely to
      reflect the heterogeneity that is seen in and around two large capital cities.
      Finally, comparison with more recently colonized areas of the world corroborates
      the genealogical origin by range expansion of several mutations.

PMID- 9012413
TI  - Characterization of recombination in the HLA class II region.
AB  - Studies of linkage disequilibrium across the HLA class II region have been useful
      in predicting where recombination is most likely to occur. The strong
      associations between genes within the 85-kb region from DQB1 to DRB1 are
      consistent with low frequency of recombination in this segment of DNA.
      Conversely, a lack of association between alleles of TAP1 and TAP2 (approximately
      15 kb) has been observed, suggesting that recombination occurs here with
      relatively high frequency. Much of the HLA class II region has now been
      sequenced, providing the tools to undertake detailed analysis of recombination.
      Twenty-seven families containing one or two recombinant chromosomes within the
      500-kb interval between the DPB1 and DRB1 genes were used to determine patterns
      of recombination across this region. SSCP analysis and microsatellite typing
      yielded identification of 127 novel polymorphic markers distributed throughout
      the class II region, allowing refinement of the site of crossover in 30 class II
      recombinant chromosomes. The three regions where recombination was observed most
      frequently are as follows: the 45-kb interval between HLA-DNA and RING3 (11
      cases), the 50-kb interval between DQB3 and DQB1 (6 cases), and an 8.8-kb segment
      of the TAP2 gene (3 cases). Six of the 10 remaining recombinants await further
      characterization, pending identification of additional informative markers, while
      four recombinants were localized to other intervals (outliers). Analysis of
      association between markers flanking HLA-DNA to RING3 (45 kb), as well as TAP1 to
      TAP2 (15 kb), by use of independent CEPH haplotypes indicated little or no
      linkage disequilibrium, supporting the familial recombination data. A notable
      sequence motif located within a region associated with increased rates of
      recombination consisted of a (TGGA)12 tandem repeat within the TAP2 gene.

PMID- 9012414
TI  - Homopolymeric tract heteroplasmy in mtDNA from tissues and single oocytes:
      support for a genetic bottleneck.
AB  - While mtDNA polymorphisms at single base positions are common, the overwhelming
      majority of the mitochondrial genomes within a single individual are usually
      identical. When there is a point-mutation difference between a mother and her
      offspring, there may be a complete switching of mtDNA type within a single
      generation. It is generally assumed that there is a genetic bottleneck whereby a
      single or small number of founder mtDNA(s) populate the organism, but it is not
      known at which stages the restriction/amplification of mtDNA subtype(s) occur,
      and this uncertainty impedes antenatal diagnosis for mtDNA disorders. Length
      polymorphisms in homopolymeric tracts have been demonstrated in the large
      noncoding region of mtDNA. We have developed a new method, T-PCR (trimmed PCR),
      to quantitate heteroplasmy for two of these tracts (D310 and D16189). D310
      variation is sufficient to indicate clonal origins of tissues and single oocytes.
      Tissues from normal individuals often possessed more than one length variant
      (heteroplasmy). However, there was no difference in the pattern of the length
      variants between somatic tissues in any control individual when bulk samples were
      taken. Oocytes from normal women undergoing in vitro fertilization were
      frequently heteroplasmic for length variants, and in two cases the modal length
      of the D310 tract differed in individual oocytes from the same woman. These data
      suggest that a restriction/amplification event, which we attribute to clonal
      expansion of founder mtDNA(s), has occurred by the time oocytes are mature,
      although further segregation may occur at a later stage. In contrast to controls,
      the length distribution of the D310 tract varied between tissues in a patient
      with heteroplasmic mtDNA rearrangements, suggesting that these mutants influence
      segregation. These findings have important implications for the genetic
      counselling of patients with pathogenic mtDNA mutations.

PMID- 9012415
TI  - Short alleles revealed by PCR demonstrate no heterozygote deficiency at
      minisatellite loci D1S7, D7S21, and D12S11.
AB  - Short VNTR alleles that go undetected after conventional Southern blot
      hybridization may constitute an alternative explanation for the heterozygosity
      deficiency observed at some minisatellite loci. To examine this hypothesis, we
      have employed a screening procedure based on PCR amplification of those
      individuals classified as homozygotes in our databases for the loci D1S7, D7S21,
      and D12S11. The results obtained indicate that the frequency of these short
      alleles is related to the heterozygosity deficiency observed. For the most
      polymorphic locus, D1S7, approximately 60% of those individuals previously
      classified as homozygotes were in fact heterozygotes for a short allele. After
      the inclusion of these new alleles, the agreement between observed and expected
      heterozygosity, along with other statistical tests employed, provide additional
      evidence for lack of population substructuring. Comparisons of allele frequency
      distributions reveal greater differences between racial groups than between
      closely related populations.

PMID- 9012416
TI  - A variant of Freeman-Sheldon syndrome maps to 11p15.5-pter.
AB  - Distal arthrogryposis type 1 (DA1) and Freeman-Sheldon syndrome (FSS) are the two
      most common known causes of inherited multiple congenital contractures. We
      recently have characterized a new disorder (DA2B) with a phenotype intermediate
      between DA1 and FSS. We report the mapping of a gene that causes DA2B to
      chromosome 11p15.5-pter. Linkage analysis in a single kindred generated a
      positive LOD score of 5.31 at theta = 0 with the marker D11S922, and recombinants
      localize the gene to an approximately 3.5-6.5-cM region between the marker TH and
      the telomere. Analysis of additional families improves the LOD score to 6.45 at
      theta = 0 and suggests linkage homogeneity for DA2B.

PMID- 9012417
TI  - Genetic effects on variation in red-blood-cell folate in adults: implications for
      the familial aggregation of neural tube defects.
AB  - Recent studies have implicated folic acid as an important determinant of normal
      human growth, development, and function. Insufficient folate levels appear to be
      a risk factor for neural tube defects (NTD), as well as for several chronic
      diseases of adulthood. However, relatively little is known about the factors that
      influence folate status in the general population. To estimate the relative
      contribution of genetic and nongenetic factors to variation in folate, we have
      evaluated red blood cell (RBC) folate levels in 440 pairs of MZ twins and in 331
      pairs of DZ twins. The data were best described by a model in which 46% of the
      variance in RBC folate was attributable to additive genetic effects, 16% of the
      variance was due to measured phenotypic covariates, and 38% of the variance was
      due to random environmental effects. Moreover, the correlations for RBC folate in
      MZ co-twins (r = .46) and in repeat measures from the same individual (r = .51)
      were very similar, indicating that virtually all repeatable variation in RBC
      folate is attributable to genetic factors. On the basis of these results, it
      would seem reasonable to initiate a search for the specific genes that influence
      RBC folate levels in the general population. Such genes ultimately may be used to
      identify individuals at increased risk for NTD and other folate-related diseases.

PMID- 9012419
TI  - Estimating the age of alleles by use of intraallelic variability.
AB  - A method is presented for estimating the age of an allele by use of its frequency
      and the extent of variation among different copies. The method uses the joint
      distribution of the number of copies in a population sample and the coalescence
      times of the intraallelic gene genealogy conditioned on the number of copies. The
      linear birth-death process is used to approximate the dynamics of a rare allele
      in a finite population. A maximum-likelihood estimate of the age of the allele is
      obtained by Monte Carlo integration over the coalescence times. The method is
      applied to two alleles at the cystic fibrosis (CFTR) locus, deltaF508 and G542X,
      for which intraallelic variability at three intronic microsatellite loci has been
      examined. Our results indicate that G542X is somewhat older than deltaF508.
      Although absolute estimates depend on the mutation rates at the microsatellite
      loci, our results support the hypothesis that deltaF508 arose < 500 generations
      (approximately 10,000 years) ago.

PMID- 9012418
TI  - Apolipoprotein E and Alzheimer disease: genotype-specific risks by age and sex.
AB  - The distribution of apolipoprotein E (APOE) genotypes as a function of age and
      sex has been examined in a French population of 417 Alzheimer disease (AD)
      patients and 1,030 control subjects. When compared to the APOE epsilon3 allele,
      an increased risk associated with the APOE epsilon4 allele (odds ratio [OR]
      [epsilon4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a
      protective effect of the APOE epsilon2 allele (OR[epsilon2] = 0.5 with 95% CI =
      0.3-0.98; P = .012) were retrieved. An effect of the epsilon4 allele dosage on
      susceptibility was confirmed (OR[epsilon4/epsilon4] vs. the epsilon3/epsilon3
      genotype = 11.2 [95% CI = 4.0-31.6]; OR[epsilon3/epsilon4] vs. the
      epsilon3/epsilon3 genotype = 2.2 [95% CI = 1.5-3.5]). The frequency of the
      epsilon4 allele was lower in male cases than in female cases, but, since a
      similar difference was found in controls, this does not lead to a difference in
      OR between sex. ORs for the epsilon4 allele versus the epsilon3 allele,
      OR(epsilon4), were not equal in all age classes: OR(epsilon4) in the extreme
      groups with onset at < 60 years or > 79 years were significantly lower than those
      from the age groups 60-79 years. In epsilon3/epsilon4 individuals, sex-specific
      lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85
      years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09-0.28) for
      women.

PMID- 9012420
TI  - Improved set of short-tandem-repeat polymorphisms for screening the human genome.

PMID- 9012421
TI  - The effect of parental gender on the GAA dynamic mutation in the FRDA gene.

PMID- 9012422
TI  - Contamination of sequence databases with adaptor sequences.

PMID- 9012423
TI  - Randomized blinded study of aprotinin infusion for liver crush injuries in the
      pig model.
AB  - Repeat exploratory laparotomies for intra-abdominal bleeding in patients who
      sustain severe blunt intra-abdominal trauma are common. Reexploration usually
      reveals no single site of bleeding and the abdomen is closed with laparotomy pad
      packing, with a presumed diagnosis of coagulopathy. These postoperative
      coagulational defects may be the result of dilution, consumption, dysfunction, or
      acquired defects of either the coagulation, fibrinolytic, or platelet systems.
      The liver plays a major role in the balance of hemostatic systems, and this
      balance is disrupted by liver trauma. This study investigates the use of
      intravenous aprotinin, a naturally occurring serine protease inhibitor, in a pig
      liver crush model to evaluate its effectiveness in reducing intra-abdominal
      bleeding in experimentally induced shock and non-shock states.

PMID- 9012424
TI  - Common duct exploration during laparoscopic cholecystectomy.
AB  - Management of a common duct stone detected during laparoscopic cholecystectomy
      remains controversial. Although endoscopic retrograde cholangiopancreatography
      with sphincterotomy is a procedure preferred by many authors, it has a reported
      15 per cent reported morbidity, 1 per cent mortality, 5 per cent failure rate,
      and 5 per cent incidence of late ampullary stenosis. Cystic duct dilatation with
      the introduction of a choledoscope and a basket remains an alternative but has a
      risk of a common duct tear and difficulty in manipulation of instrument should
      the cystic duct enter the common duct at an angle, and it causes difficulty in
      extraction of larger stones. In our experience, a choledochotomy with removal of
      stones during the laparoscopic cholecystectomy is a satisfactory direct approach.
      We reviewed all of the cholecystectomies performed in the regional hospital since
      the introduction of the laparoscopic technique. There were 425 cases of
      laparoscopic cholecystectomies performed with cholangiography, with detection of
      a stone in 11 patients. In these patients, choledochotomies were performed by
      making an incision on the anterior surface of the common duct using scissors. The
      cystic duct should not be divided following cholangiography since provided
      traction. Following exploration using a Fogarty catheter, a T tube was placed,
      and a T tube cholangiogram was performed prior to its removal. With this
      technique, we successfully removed the stones in 10 cases. In one, an impacted
      stone was removed in the X-Ray Department, 6 weeks postoperative and enables
      cholecystectomy and bile duct stones to be removed in one session with no
      increase in morbidity or mortality.

PMID- 9012425
TI  - Effect of macrophage stimulation on collagen biosynthesis in the healing wound.
AB  - Immunomodulators that enhance macrophage function have been shown to be
      beneficial in a number of wound-healing models in humans and in experimental
      animals. The exact mechanism of this improved healing is unclear. To assess the
      role of collagen biosynthesis, the immunomodulator glucan phosphate was utilized
      in two murine models of wound healing, i.e., colon anastomosis and full-thickness
      skin incision. Tensile strength was evaluated using computer-assisted constant
      velocity tensiometry. Collagen biosynthesis was determined by assaying
      hydroxyproline content of wound hydrolysates by N-(9-fluorenyl)methoxycarbonyl/o
      phthalaldehyde high-performance liquid chromatography. Experimental animals were
      treated with (1-3)-beta-D-glucan phosphate (250 mg/kg) intravenously 24 hours
      prior to colon anastomosis or skin incision. A second dose of glucan phosphate
      was given immediately postoperatively. Control animals received dextrose and
      water (5% w/v) intravenously. Tensile strength and hydroxyproline content were
      measured on postoperative Day 3. In the skin wound model, glucan phosphate
      treatment increased (P < 0.05) tensile strength by 42 per cent (342.5 +/- 12.2 vs
      241.8 +/- 4.8 g), and hydroxyproline content was increased by 23.5 per cent
      (242.0 +/- 14.4 vs 196.8 +/- 10.5 pmol/microg; P < 0.05). In the glucan phosphate
      group, colon tensile strength was significantly (P < 0.05) increased by 34 per
      cent (34.2 +/- 2.3 g vs 45.8 +/- 2.1 g), and hydroxyproline content was increased
      by 7 per cent (47.45 +/- 3.31 vs 44.34 +/- 3.74 pmol/microg). These data indicate
      that macrophage modulation with glucan phosphate will increase tensile strength
      in experimental colon and skin wounds. In addition, we observed a positive
      correlation between glucan phosphate treatment, wound tensile strength, and
      collagen biosynthesis.

PMID- 9012426
TI  - Incidence and significance of subdiaphragmatic air following laparoscopic
      cholecystectomy.
AB  - Subdiaphragmatic free-air may be indicative of a perforated viscus; however, it
      is normally present after open abdominal surgery. The objective of this study was
      to determine the significance and incidence of subdiaphragmatic free air
      following laparoscopic cholecystectomy (LC). Cases of intestinal perforation
      following laparoscopic cholecystectomy from 1991 to 1995 at The University of
      Texas Health Science Center at San Antonio were reviewed and their association
      with subdiaphragmatic free air was determined. Twenty-five patients undergoing LC
      and 20 patients undergoing open cholecystectomy (OC) were prospectively evaluated
      with chest radiographs to determine the incidence and quantity of nonpathologic
      postoperative free air. Four cases of intestinal perforation resulting from
      trocar injuries or electrocautery burns occurred among 1603 LCs during this study
      period, for an incidence of 0.2 per cent. Three of the four patients with
      perforations were diagnosed postoperatively (2-5 days), and two patients had a
      moderate volume of subdiaphragmatic free air that aided the diagnosis. The
      incidence of subdiaphragmatic air following LC was 24 per cent, compared to 60
      per cent for OC (P < 0.05). Eighty-three per cent of patients with retained air
      after LC had a minimal volume, compared to 67 per cent of patients after OC (P <
      0.05). Nonpathologic subdiaphragmatic free air may normally be present following
      laparoscopic cholecystectomy but is uncommon 24 hours after the operation. When
      present, only a small volume is usually detectable. In the rare situation of
      intestinal perforation resulting from LC, subdiaphragmatic free air may be an
      important diagnostic finding.

PMID- 9012427
TI  - Treatment and prevention of malignant ascites associated with disseminated
      intraperitoneal malignancies by aggressive combined-modality therapy.
AB  - No satisfactory treatment exists to treat or prevent malignant ascites secondary
      to nonovarian intraperitoneal (IP) disseminated malignancies. A Phase I/II
      clinical trial combining radical cytoreductive surgery (CS) and IP hyperthermic
      chemotherapy (IPHC) with mitomycin C is presented. Between December 9, 1992 and
      July 31, 1995, 39 patients (pts) were explored for IP cancer. Five pts with known
      liver metastases were excluded, leaving 34 pts (15 female, 19 male) of median age
      53 (range, 17-76). The majority of pts had disseminated IP cancers of
      gastrointestinal origin (80%). Prior therapy included the following:
      chemotherapy, 20 pts (59%); surgery, 29 pts (85%); and radiation, 2 pts (6%).
      Following CS, IPHC with mitomycin C was done. At surgery, 12 pts (35.3%) had
      frank ascites, and 12 pts (35.3%) had positive IP cytology without ascites. The
      median hospital stay was 9 days (range, 5-65) with no 30-day mortality.
      Complications for 36 treatments included: thrombocytopenia Eastern Cooperative
      Oncology Group grade 3 or 4, two cases (5.6%); neutropenia requiring granulocyte
      colony-stimulating factor, seven cases (19.4%); sepsis, four cases (11.1%); bowel
      leak, two cases (5.6%); and serous wound leak, two cases (5.6%). Ascites
      correlated with worse resection status (P = 0.025). Ascites was controlled in 9
      of 12 (75.0%) pts, with failures at 1, 4, and 14 months (median follow-up, 7.5
      months). No cytology-positive ascites-negative pts developed clinical ascites
      (median follow-up, 9.4 months). The median survival time in pts with ascites was
      10.1 months versus 32.7 for patients without ascites (P = 0.013). For the entire
      study population, the 1- and 2-year survival rates were 74.6 and 48.5 per cent,
      respectively (median follow-up, 18.2 months). In this study, malignant ascites
      was controlled in 75 per cent of cases and prevented in all pts with positive IP
      cytology. CS plus IPHC appears to be relatively well tolerated and may be
      effective for the treatment and prevention of malignant ascites.

PMID- 9012428
TI  - Axillary lymph node metastasis in stage T1a breast cancer: a pathologic review of
      82 patients.
AB  - The recent shift toward the diagnosis of smaller breast cancers has led to the
      reevaluation of their treatment. Because of the low incidence of nodal
      involvement, recent studies have recommended selective axillary lymph node
      dissection (AxLND) for early breast cancer. The incidence of nodal involvement is
      a critical factor in defining the role of AxLND. Large series based on cancer
      registry data report the incidence of nodal positivity in stage T1a cancer to be
      16 to 23 per cent. In contrast, data that include only pathologically reviewed
      cases report the incidence to be 0 to 6 per cent. We reviewed the medical records
      of 148 stage T1a breast cancer patients from 1987 through 1994 in two community
      hospitals as identified by the local tumor registry. After chart review, 115
      cases with AxLND underwent pathologic review; 82 were confirmed as stage T1a.
      Only 3 of 82 (4%) patients were node positive. All three node-positive tumors
      were of infiltrating ductal histology. No tumor characteristic was predictive of
      nodal metastasis. Data from the tumor registry and from pathology reports
      overstated the incidence of nodal involvement (5 and 9%, respectively). In light
      of the limited clinical benefit and associated cost and morbidity of AxLND,
      selected informed patients may be spared AxLND.

PMID- 9012429
TI  - Intraoperative cholangiography in laparoscopic cholecystectomy: a review of 734
      consecutive cases.
AB  - Intraoperative cholangiography was first introduced by Mirizzi in 1931. He
      recommended its routine use. The debate over the appropriate role of
      intraoperative cholangiography was renewed by the widespread acceptance of
      laparoscopic cholecystectomy in 1988. We reviewed our experience to determine the
      most appropriate use of intraoperative cholangiography. Seven hundred thirty-four
      consecutive cases of laparoscopic cholecystectomy performed between January 1,
      1991 and December 31, 1993 were reviewed. The Routine Group of 276 cases,
      performed by 3 surgeons practicing routine cholangiography, was compared to the
      Selective Group of 458 cases, performed by 16 surgeons practicing selective
      cholangiography. The groups were similar in terms of age, sex, and extent of
      disease. No statistically significant difference was found between the two groups
      in number of successful cholangiograms, filling defects, misinterpretation of
      cholangiograms, complications, or length of hospitalization. One common duct
      injury occurred in the Routine Group. The rate of conversion to open
      cholecystectomy was higher in the Routine Group. A cholangiogram added 14 minutes
      to the average duration of surgery and $737 to the average cost. We found that
      routine cholangiography did not increase common duct stone detection, did not
      decrease common duct injury, and did not increase technical skill, but it did
      increase cost. We feel that intraoperative cholangiography should be used
      selectively where choledocholithiasis is suspected or biliary anatomy is unclear.

PMID- 9012430
TI  - Peritoneovenous shunts in patients with intractable ascites: palliation at what
      price?
AB  - Intractable ascites carries great morbidity by affecting appetite, mobility, and
      quality of life. Peritoneovenous shunts (PVSs) are utilized to abate intractable
      ascites, although long-term efficacy is unestablished. Thirty male and 18 female
      cirrhotics, 55 +/- 12 (standard deviation) years of age, failed multiple large
      volume paracenteses and diuretic therapy before undergoing PVS. Data were
      collected until death or the present time. Nine patients (19%) are alive and
      palliated, four with working shunts [average follow-up (ave. f/u), 30 months] and
      five without shunts (ave. f/u, 19 months). Thirty-two (67%) patients died: 18
      palliated with functional shunts (survival time, 4.4 +/- 5.7 months), 8
      unpalliated with dysfunctional shunts (ave. f/u, 3.9 +/- 4.5 months), 4
      unpalliated with shunts removed (ave. f/u 5.5 +/- 4.7 months), and 2 with unknown
      shunt function at death. Function was lost to occlusion in 26 patients, infection
      in 9, and ligation for disseminated intravascular coagulation in 3. Thirteen
      patients underwent 18 shunt replacements. At death/present time, 22 (46%)
      patients were palliated with functioning shunts. Seven patients were lost to
      follow-up. PVSs provide palliation for intractable ascites short term, but
      commonly occlude within 1 year. Despite palliation, complications with PVSs are
      high, and survival is limited.

PMID- 9012431
TI  - Surgical implications of hypercoagulable syndromes.
AB  - The advent of improved diagnostic tests for primary hypercoagulability has led to
      increased recognition of this entity as a problem in surgical patients. We
      treated 20 patients with documented evidence of increased coagulability from 1975
      to 1995. Clinical presentations included venous (16) and arterial (4) thrombosis.
      Symptoms usually occurred early in life (mean age, 38 years) and developed
      spontaneously without a secondary inciting event or factor. Deficiencies in
      naturally occurring anticoagulant proteins including antithrombin III (n = 7),
      protein C (n = 3), and protein S (n = 1) were seen, as were problems with lupus
      anticoagulant (n = 2) and anticardiolipin antibody (n = 4) deficiencies.
      Treatment of these patients is difficult, and results are often suboptimal. A
      total of 12 vascular reconstructions were required in 5 of the 20 patients; 11
      eventually failed. Patients with primary venous thrombosis were often
      successfully treated with anticoagulant therapy in the short term but fared less
      well in the long term. There were three deaths directly related to thrombotic
      complications. Surgeons may encounter patients with primary hypercoagulable
      syndromes. The diagnosis should be expected in patients with unusual patterns of
      vascular disease or arterial or venous thrombosis without cause or at an early
      age, or in patients with recurrent or migratory clotting. Evaluation of this
      population, although expensive, is indicated. Treatment with chronic
      anticoagulation is also generally indicated. Arterial reconstruction in this
      subset of patients usually leads to a poor outcome.

PMID- 9012432
TI  - Primary repair of 58 consecutive penetrating injuries of the colon: should
      colostomy be abandoned?
AB  - Although primary repair of penetrating colon injuries in patients with low injury
      severity is now widely accepted, several "risk factors" continue to be viewed as
      relative contraindications to this method of management. The purpose of this
      study was to evaluate the septic complications and leak rate in a series of
      consecutive penetrating colon injuries managed exclusively with primary repair.
      The records of 58 consecutive patients with penetrating intra-abdominal colon
      injuries managed at an urban Level I trauma center from July 1991 to December
      1995 were reviewed. Patients were stratified for injury severity using the
      Penetrating Abdominal Trauma Index (PATI), and the presence of "risk factors" and
      septic abdominal and wound complications were recorded. All 58 patients were
      managed with primary repair. There were 48 gunshot wounds (72%), 7 shotgun wounds
      (12%), and 9 stab wounds (16%) with a mean PATI of 26.7 +/- 15.2 standard
      deviation. Seven patients (12.1%) developed intra-abdominal abscess, and all were
      managed by CT-guided percutaneous drainage. Five patients (8.6%) developed
      bacteremia, and eight patients (13.8%) developed fascial dehiscence. Three
      patients (5.2%) underwent abdominal re-exploration in the postoperative period,
      but none of these was related to failure of the colonic repair. There were no
      clinically apparent leaks or fistulae and no deaths. The presence of "risk
      factors" appeared to identify more severely injured patients as indicated by a
      higher mean PATI score and a higher incidence of intra-abdominal abscess, when
      compared to patients in whom the "risk factor" was absent. Primary repair can
      safely be used for virtually all penetrating colon injuries, as clinical leaks
      are rare, even in patients with "risk factors". Intra-abdominal abscess and other
      septic complications are dependent on the overall severity of the intra-abdominal
      injuries and probably result from contamination occurring at the time of injury
      rather than from postoperative leak from the primary repair.

PMID- 9012433
TI  - Predictors of survival after inferior vena cava injuries.
AB  - In patients with inferior vena cava (IVC) injuries, predictors of survival are
      investigated. From 1987 to 1995, 27 IVC injuries were identified among 514
      patients with vascular trauma. The ability of clinical determinants to predict
      survival were retrospectively assessed. IVC injuries occurred in 7 females and 20
      males (mean age, 27.7 +/- 2.5 years) from both blunt (n = 14) and penetrating (n
      = 13) trauma. The mean revised trauma score was 10.2 +/- 0.6. Injuries were
      treated by primary repair (n = 22), ligation (n = 4), or prosthetic grafting (n =
      1). Thirteen patients died (48%), 10 within 12 hours of admission. Suprahepatic
      (n = 2), retrohepatic (n = 12), suprarenal (n = 1), and infrarenal (n = 12)
      injuries were associated with 100, 67, 100, and 20 per cent mortality,
      respectively. Blood transfusions (16 +/- 4 vs 23 +/- 4 units), coagulation factor
      replacement (7 +/- 2 vs 7 +/- 2 units), and electrolyte solution use (8.6 +/- 1.4
      vs 9.6 +/- 1.4 L) were similar among survivors and nonsurvivors. Four
      complications [venous hypertension (n = 2), IVC thrombosis (n = 1), and pulmonary
      embolus (n = 1)] occurred in the 14 survivors (28.6%). Blunt injury, revised
      trauma score, free perforation, injury location, intraoperative hypotension, and
      blood loss were predictive of mortality. IVC injuries remain extremely lethal,
      and improved survival is associated with infrarenal penetrating injuries and a
      contained hematoma.

PMID- 9012434
TI  - The role of ultrasonography in blunt abdominal trauma: a prospective study.
AB  - The evaluation of blunt abdominal trauma (BAT) can be difficult because of the
      subtle manifestations of the injuries and because assessment is hampered by
      altered neurologic status. Short of laparotomy, CT and diagnostic peritoneal
      lavage provided the best means of accurately diagnosing intra-abdominal injury.
      Ultrasound (US) has recently been introduced into trauma centers in the United
      States as a quick, cheap, and safe method to make the diagnosis of BAT. After
      theoretical and practical training, one attending surgeon and one chief resident
      began performing trauma ultrasounds at a rural, Level 1 trauma center. The US was
      performed concurrent with initial resuscitation and prior to other studies. The
      US was then correlated with the other tests. Of the 82 tests performed, 79
      correlated with other methods of diagnosis. Overall, US was 88 per cent
      sensitive, 98 per cent specific, and 96 per cent accurate in diagnosing intra
      abdominal injuries. There were no operative sequelae to patients whose injury was
      missed by US. We conclude that: 1) US can be used as the initial method of
      diagnosis of BAT and 2) surgeons are able to perform the examination accurately.

PMID- 9012435
TI  - Penetrating injuries of the neck: selective management evolving.
AB  - Since 1990, a selective management algorithm has been used in our Trauma Center
      to treat 91 patients with penetrating neck injuries. Group A (n = 37) sustained
      zone I, zone III, or multiple-zone injuries; Group B (n = 54) sustained zone II
      injuries [most (55, 66.4%) from gunshot or shotgun wounds]. Nineteen Group A and
      21 Group B patients required mandatory neck exploration. Vascular or
      aerodigestive tract injuries were found and adequately repaired in 15 Group A and
      11 Group B patients. The superficial wounds of three Group A and seven Group B
      patients were closed, and the patients were observed for 24 hours. The remaining
      15 Group A and 24 Group B patients underwent routine angiogram, arbitrary barium
      swallow, and, if necessary, esophagoscopy. Two of these Group B patients required
      surgery for common carotid artery injuries. One patient died 4 months later
      because of missed vertebral artery pseudoaneurysm. Overall mortality and
      complication rates were 6 and 1 per cent. Unnecessary exploration was avoided in
      52 per cent of cases regardless of the location of the wound. Mortality and
      morbidity rates were acceptable. Patients with penetrating neck injuries could be
      safely managed selectively regardless of the injury zone.

PMID- 9012436
TI  - In vivo uptake of technetium-99M-sestamibi by parathyroid glands in comparison to
      surrounding tissues of the neck.
AB  - Technetium-99M-sestamibi (Tc-99M-sestamibi) has recently been proven to be a
      sensitive and specific agent for imaging of parathyroid disease; however, the
      selective nature of its uptake by different tissues has not been investigated.
      Fifteen consecutive patients undergoing neck exploration for hyperparathyroidism
      were given 3 to 15 mCi of Tc-99M-sestamibi at various times before surgery, and
      at the time of exploration, samples of parathyroid tissue, blood, fat, muscle,
      and thyroid were taken from the neck. All samples were carefully weighed and
      counts of radioactivity were measured. Activity was normalized to counts per gram
      of tissue and counts of radioactivity were compared using a multiple range
      analysis of variance test. Mean counts per gram (+/- SE) in abnormal parathyroid
      tissue (adenomas and hyperplastic glands; 1.1 x 10(6) +/- 2.7 x 10(6)) were
      significantly higher than in any of the other tissues measured (P < 0.05):
      thyroid, 7.0 x 10(4) +/- 1.6 x 10(4); muscle, 8.9 x 10(4) +/- 2.1 x 10(4); fat,
      2.1 x 10(4) +/- 4.2 x 10(3); and blood, 9.8 x 10(3) +/- 2.3 x 10(3). Mean ratios
      of counts (+/- SE) of abnormal parathyroid tissue to other tissues were found to
      be as follows: thyroid, 35.3 +/- 12.6; muscle, 17.4 +/- 6.2; fat, 80.7 +/- 20.0;
      and blood, 161.0 +/- 31.6. From these data, Tc-99M-sestamibi clearly exhibits
      significantly higher uptake in abnormal parathyroid tissue relative to other
      tissues measured in the neck. This increased uptake in parathyroid gland tissue
      accounts for the utility of Tc-99M-sestamibi in localization studies for
      hyperparathyroidism. Quantification of in vivo uptake of Tc-99M-sestamibi may
      help refine techniques for improved localization of hyperfunctional parathyroid
      glands.

PMID- 9012437
TI  - Nonoperative therapy for postcatheterization femoral artery pseudoaneurysms.
AB  - Since November 1992, 160 patients were referred to the Vascular Surgery
      Laboratory for duplex scanning to assess whether a femoral artery pseudoaneurysm
      was present. Of these patients, 33 per cent (n = 53) had femoral artery
      pseudoaneurysms with maximal diameters ranging from 1.5 to 8.1 cm. Most
      pseudoaneurysms (79%; 42 of 53) followed diagnostic or therapeutic cardiac
      catheterization procedures. Pseudoaneurysms were treated by external compression
      using an ultrasound probe in 33 of these 53 patients, and thrombosis of the
      aneurysm was successfully induced in 76 per cent (n = 25) of those in whom
      nonoperative external compression therapy was attempted. Of the eight patients in
      whom compression was unsuccessful, three had severe pain that required cessation
      of compression, and femoral nerve involvement by the pseudoaneurysm was noted at
      surgery in two of the three. One additional patient refused a second attempt at
      compression due to discomfort. Of the other four failures of compression, four
      (50% overall) received anticoagulants during or prior to compression. In 25
      patients with successful pseudoaneurysm thrombosis after external compression,
      none had severe pain from compression, and 40 per cent (n = 10) were on
      anticoagulants until or during compression. Four of the 53 (7.5%) pseudoaneurysms
      diagnosed in the vascular laboratory subsequently thrombosed spontaneously, and
      two patients (3.8%) experienced pseudoaneurysm rupture. Thrombosis of
      postcatheterization pseudoaneurysms can be achieved by nonoperative compression
      therapy in most patients. Severe pain during external compression suggests
      possible femoral nerve involvement by the pseudoaneurysm and is an indication for
      surgical therapy.

PMID- 9012438
TI  - Identification of antigenic sites on staphylococcal enterotoxin B and toxoid.
AB  - The staphylococcal enterotoxins (SEs) are capable of causing both food poisoning
      and a toxic shock-like illness in man. In addition, SEs are known to act as
      superantigens, stimulating T-cells according to their T-cell receptor Vbeta type.
      Relatively little is known of their antigenic determinants and how these may
      relate to the structure and function of the toxins. As a step in the study of
      these relationships, the entire molecule of SEB was synthesized in duplicate as a
      series of octapeptides overlapping by seven residues. This series thus
      represented all the potential linear epitopes of eight residues or less. The
      reactivity of the octapeptide series with antisera raised to purified SEB and to
      formaldehyde-inactivated SEB has been used to locate several antigenic sites on
      native SEB and to identify antigenic differences in the toxoid. Three antigenic
      peptides identified from the antigenic profile were synthesized and
      characterized. These represented amino acids 21-32, 93-107 and 202-217 of SEB.
      None of these peptides affected SEB-induced T-cell proliferation. However, the
      occurrence or absence of cross-reactivity of these peptides with antibodies to
      native SEB corresponds to the degree of exposure and/or the rigidity of these
      regions within SEB.

PMID- 9012439
TI  - Crossreactions and sequence homologies between recombinant polypeptides from
      Leishmania aethiopica and human IgG and IgM.
AB  - Recombinant DNA fragments M (154 bp) and G (206 bp), coding for recombinant
      polypeptides that crossreact with human IgM and IgG, have been isolated from a
      genomic library of Leishmania aethiopica. Epitope scanning of the two recombinant
      polypeptides, using overlapping octapeptides, revealed several crossreactive
      epitopes present in both recombinant proteins. By comparing amino acid sequences,
      similar sequences in human mu and gamma immunoglobulin heavy chains were
      identified. One of the parasite octapeptides is identical to an octapeptide in
      gamma1 covering the Gm(a) allotypic marker. Expression of both the M and G
      fragments was detected in the parasites by RT-PCR of total mRNA, using primers
      specific for these fragments. Preliminary data showed that the presence of
      autoimmune anti-IgG antibodies was more pronounced in sera from patients with
      diffuse cutaneous leishmaniasis than in sera from patients with localised
      cutaneous leishmaniasis. We suggest that these immunoglobulin-crossreacting
      epitopes potentially might contribute to the induction of rheumatoid factors and
      be involved in the interplay between the parasite and the host immune system.

PMID- 9012440
TI  - Rapid and differential detection of two analogous enterotoxins of Vibrio cholerae
      and enterotoxigenic Escherichia coli by a modified enzyme-linked immunosorbent
      assay.
AB  - The principle of a novel ELISA (nylon-slip immuno-test, NSIT) was applied to the
      differential detection of two analogous enterotoxins, cholera toxin (CT) of
      Vibrio cholerae and heat-labile enterotoxin (LT) of enterotoxigenic Escherichia
      coli. The results obtained for CT and LT detection by a single test were
      sufficiently sensitive (87.9 and 100%) and specific (100 and 94.7%) in the
      differential detection test, when compared with the result of a colony
      hybridization test with DNA probes. The results suggest that the novel ELISA is
      applicable to the diagnosis of bacterial infections, by means of differential
      immunological detection of toxins in a single test.

PMID- 9012441
TI  - Effect of Escherichia coli L-form cytoplasmic membranes on the interaction
      between macrophages and Lewis lung carcinoma cells: scanning electron microscopy.
AB  - Scanning electron microscopy (SEM) investigations on the interactions between
      peritoneal macrophages from Lewis lung carcinoma (LLC)-bearing mice and LLC
      tumour cells during 21 days after tumour implantation were carried out. The
      action of lipopolysaccharide (LPS)-containing cytoplasmic membranes (CM), from
      the stable protoplast type L-form of Escherichia coli, on the activity of in
      vitro phagocytosis was studied; CM induced a continuous increase in macrophage
      numbers. Activation of macrophage surfaces in healthy and tumour-bearing mice was
      established. Lamelipods, pseudopods and migration fringes 14 days after CM
      application were seen. Crater-like cavities deeply in the macrophage cells as
      well as adherent or prominent engulfed tumour cells within macrophages were
      observed during in vitro interaction with LLC cells. Macrophages from tumour
      bearing mice without CM treatment showed less activation evaluated by SEM during
      earlier stages of tumour growth. The SEM investigation proved the temporary
      stimulating effect of E. coli L-form CM on the cell surface activation of
      peritoneal macrophages in healthy and LLC-bearing mice.

PMID- 9012442
TI  - Arbitrary primed PCR fingerprinting and serotyping of clinical Pseudomonas
      aeruginosa strains.
AB  - Arbitrary primed PCR (AP-PCR) analysis was compared with serotyping as a means of
      high-resolution typing of Pseudomonas aeruginosa. Seventy-four isolates from 3
      different hospitals and 18 reference strains were studied. Serotyping provided
      good index of discrimination, although eleven isolates could not be serotyped.
      Genomic DNA was amplified with a single 10 nucleotide primer (sequence 5'-AGG GGT
      CTT G-3'). The strains were genetically diverse and 61 different AP-PCR profiles
      of 2-7 bands between 0.3 and 2.4 kb were obtained. AP-PCR profiles were not
      consistently associated with serotypes, but they clearly subtyped strains of the
      same serotype. Numerical analysis of AP-PCR patterns defined 7 groups at the 55%
      similarity level, and identified predominant strains in each hospital. The
      results show that AP-PCR analysis provides a simple and practical approach to
      typing P. aeruginosa that is more discriminatory than traditional serotyping
      scheme. We suggest that maximum discrimination can be achieved by a combination
      of both methods.

PMID- 9012443
TI  - Micrococcus luteus cells and cell walls induce anaphylactoid reactions
      accompanied by early death and serum cytokines in mice primed with muramyl
      dipeptide.
AB  - Micrococcus luteus strains at a dose of 500 microg of whole cells caused
      anaphylactoid reactions leading to death in some instances within 1 h in C3H/HeN
      mice primed with muramyl dipeptide (MDP, 100 microg). Tumor necrosis factor (TNF)
      and interleukin-6 (IL-6) were induced in the serum of half and of all the
      surviving mice, respectively. Cell wall specimens of M. luteus so far examined
      also caused anaphylactoid reactions accompanied by early death and one strain
      induced high levels of TNF and IL-6. Cytoplasmic membranes also induced IL-6.
      Essentially similar results were obtained with representative M. luteus cells and
      a cell wall specimen in MDP-primed C3H/HeJ mice. These results indicate that M.
      luteus has virulence activities that are associated with the induction of septic
      shock and systemic inflammatory diseases.

PMID- 9012444
TI  - The oxidative burst triggered by Salmonella typhimurium in differentiated U937
      cells requires complement and a complete bacterial lipopolysaccharide.
AB  - The bacterial and serum factors involved in the oxidative response triggered by
      Salmonella typhimurium in differentiated U937 cells were investigated. Complement
      activation was shown to be required, using sera deficient in complement factors.
      An original dot-blot technique was developed to study the activation of
      complement by either bacteria or purified lipopolysaccharide (LPS). Both O
      specific and lipid A segments of LPS were found to play a role in the triggering
      of the oxidative response. Lipid A was responsible for bacterial C3-derived
      opsonization by inducing an antibody-independent activation of complement
      classical pathway, whereas O-specific polysaccharide chains (O-Ag) were involved
      in cellular activation. Inhibition experiments using anti-cell surface marker
      monoclonal antibodies showed the involvement of the alpha chain of CR3 (CD11b) in
      the oxidative response developed by differentiated U937 cells in response to S.
      typhimurium infection. Whether both iC3b and O-Ag interact with different domains
      of CR3 or whether the binding of O-Ag occurs via a not yet identified receptor
      remains to be determined.

PMID- 9012445
TI  - Efficiency of retroviral transduction into hematopoietic cells by cocultivation
      procedure does not correlate with viral titer.
AB  - Relative transduction efficiency with retroviral vector-producing clones was
      assayed by cocultivating TF-1, a human CD34+ hematopoietic cell line and YR-2, a
      sheep B-lymphoid cell line, with LacZ containing vector-producing cells, and then
      by scoring the percentage of X-Gal+ cells. At the same time, viral titer was
      estimated by titration assay with murine fibroblasts. Results clearly
      demonstrated a lack of correlation between viral titer and efficiency of
      transduction into hematopoietic cells, which depends neither on the type of
      packaging cell line, PG-13 and GP-envAM12 in this study, nor on the type of LacZ
      containing retroviral vector. These results strongly favor consideration of
      interactions between producers and target cells of the study for the screening of
      producing cell lines.

PMID- 9012446
TI  - Liver-associated toxicity of the HSV-tk/GCV approach and adenoviral vectors.
AB  - Intravenous injection of immunodeficient mice with adenoviral vectors carrying
      the HSV-tk gene led to preferential transduction of liver tissue. Subsequent
      application of ganciclovir (GCV) resulted in extremely high toxicity with
      negligible survival rates. This toxicity was only seen when GCV was applied in
      addition to the adenoviral vector and not if combined with the Ad-beta gal
      control vector. This indicates a specific Ad-tk/GCV-related toxicity. Low
      survival rates were seen not only after intravenous administration but also after
      injection of the vectors into the portal vein, the liver tissue and liver tumors,
      but not during the treatment of subcutaneous tumors. This, together with
      extensive signs of liver degeneration occurring as early as one day after the
      initiation of GCV treatment, strongly suggests a specific liver-associated
      toxicity. Severe toxicity was observed when animals received GCV treatment as
      late as 7 weeks after vector administration. Moreover, in vitro survival rates of
      resting primary hepatocytes treated with Ad-tk and GCV were very low. We
      therefore suppose a mechanism of toxicity of phosphorylated GCV which is
      independent from cellular proliferation. Since our results indicate that the Ad
      HSV-tk/GCV approach is toxic for the resting liver, additional safety features
      such as tumor-restricted transgene expression should be included in adenoviral
      vectors.

PMID- 9012447
TI  - A comparison of gene transfer methods in human dendritic cells.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for the
      initiation of antigen-specific T-cell activation. DCs may be highly enriched from
      peripheral blood-adherent leukocytes by short-term (7-day) culture in the
      presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating
      factor. Various methods of gene transfer were studied, including DNA/liposome
      complexes, electroporation, CaPO4 precipitation, and recombinant adenovirus (AdV)
      vectors. Low levels of expression were obtained with the physical methods tested.
      In contrast, AdV vectors expressing luciferase, beta-galactosidase, IL-2, and IL
      7 all readily transduced human DCs. Increasing levels of gene expression were
      observed over a range of multiplicity of infection (MOI) of 10:1 to 10,000:1,
      with transduction efficiencies exceeding 95% at higher MOI. Although levels of
      maximal gene expression in DCs were significantly lower than those obtained using
      human tumor cell lines, IL-2 and IL-7 production of up to 5 x 10(2) ng/10(6) DC
      were achieved. These results suggest that AdV vectors are a promising vehicle for
      genetically engineering human DCs.

PMID- 9012448
TI  - Retrovirally mediated gene transfer of Arg22 and Tyr22 forms of dihydrofolate
      reductase into the hematopoietic cell line K562: a comparison of methotrexate
      resistance.
AB  - Mutations in the enzyme dihydrofolate reductase (DHFR) can confer resistance to
      the inhibitory effects of folate analogs such as methotrexate (Mtx) and
      trimetrexate (Ttx). Retroviral vectors expressing the DHFR-Arg22 mutants and the
      newly described DHFR-Tyr22 mutant were used to transduce the hematopoietic cell
      line K562. In vitro selection of vector-containing cells was documented via
      polymerase chain reaction and Southern analysis. When proliferation of selected
      vector-containing cells was evaluated over a range of Mtx concentrations (0.01 to
      10 micromol/L), both Arg22 and Tyr22 provided protection from Mtx, but Tyr22
      proved superior to Arg22 in conferring Mtx resistance at low concentrations. Ttx
      proved to be 10- to 100-fold more potent than Mtx in inhibiting proliferation of
      nontransduced K562, but the relative effectiveness of individual mutants in
      conferring drug resistance was similar to that of Mtx. Decreasing the amount of
      folate in the culture medium to more physiological concentrations increased the
      potency of administered Mtx and Ttx. Drug resistance in retrovirally transduced
      K562 cells is consistent with the enzymatic characteristics of the individual
      mutants. Our findings suggest that the new Tyr22 form of DHFR may prove better in
      conferring drug resistance than the previously reported Arg22 mutant.

PMID- 9012449
TI  - Eradication of melanoma pulmonary metastases by immunotherapy with tumor cells
      engineered to secrete interleukin-2 or gamma interferon.
AB  - This study was undertaken to investigate the effectiveness of interleukin-2 (IL
      2) and gamma interferon (gammaIFN)-modified B16 melanoma cells in the
      immunotherapy of established melanoma pulmonary metastases. The genes for IL-2
      and gammaIFN were introduced retrovirally into B16 melanoma cells. Transduction
      with the gammaIFN, but not the IL-2, gene caused significant increases in the
      expression of major histocompatibility complex (MHC) antigens on B16-gammaIFN
      cells. The in vivo tumor-forming capacity of both IL-2- and gammaIFN-transduced
      B16 cells was drastically reduced when the cells were inoculated subcutaneously
      (SC) in syngeneic C57BL/6 mice. After intravenous (IV) inoculation, most of the
      B16-gammaIFN cells were rejected, but B16-IL-2 cells were relatively tumorigenic
      and formed pulmonary metastases. C57BL/6 mice bearing 4-day established parental
      B16 lung metastases were treated with B16 parental (B16P) unmodified cells, IL-2-
      or gammaIFN-modified B16 cells, or a combination of both transduced cells.
      Treatment consisted of a weekly intraperitoneal (IP) injection of one million
      irradiated (10,000 rad) tumor cells alone or in combination with exogenous IL-2
      for a total of three to four injections. Immunotherapy with B16 parental or B16
      IL-2 secreting cells caused a moderate reduction in the number of lung
      metastases. However, mice treated with gammaIFN-secreting B16 cells showed a
      significant reduction or complete elimination of lung metastases. There was no
      additive effect for combining both IL-2- and gammaIFN-modified tumor cells in the
      immunotherapy. Exogenous IL-2 (50,000-100,000 U/day for 3 days) caused a
      significant enhancement of the immunotherapeutic benefit of the vaccines.
      Moreover, mice treated with gammaIFN-modified B16 cells survived longer than the
      other groups. Twenty-five percent of these mice were tumor free and remained
      alive for an observation period of 4 months. The in vitro cytolytic activity of
      splenocytes in chromium release assays did not correlate in every case with the
      in vivo antitumor effect of the treatment. Our findings have implications for the
      use of cytokine-modified cells for immunotherapy and for evaluating the
      therapeutic benefit of this novel treatment.

PMID- 9012450
TI  - Expression of an antisense transforming growth factor-beta1 transgene reduces
      tumorigenicity of EMT6 mammary tumor cells.
AB  - Transforming growth factor-beta (TGF-beta) is a potent immunosuppressive cytokine
      produced by many tumor cells. Secretion of TGF-beta by malignant cells may
      therefore be a mechanism by which tumor cells escape destruction by tumor
      specific T lymphocytes. In order to evaluate the role of tumor-derived TGF-beta
      on tumor progression, we have inhibited the production of this cytokine by
      introducing a gene encoding antisense TGF-beta1 into the EMT6 murine mammary
      tumor cell line using a retroviral vector (Las-TGF-beta1SN). EMT6 cells
      transduced with this vector (EMT6as-TGF-beta1) stably expressed the antisense
      gene and secreted 52% less TGF-beta than did tumor cells transduced with the
      backbone vector alone. Supernatant fluid recovered from tumor cells expressing
      the antisense TGF-beta1 gene also exhibited a decreased capacity to inhibit
      alloantigen-specific cytotoxic T-cell responses in vitro. Furthermore, tumor
      growth in mice injected with EMT6as-TGF-beta1 tumor cells was inhibited compared
      to mice injected with control tumor cells. These results demonstrate that
      expression of antisense TGF-beta1 by transduced EMT6 cells decreases their
      tumorigenicity and suggest that this approach of eliminating immune suppression
      is a potentially useful strategy to enhance antitumor responses.

PMID- 9012451
TI  - Coexpression of a multidrug resistance gene (MDR1) and herpes simplex virus
      thymidine kinase gene in a bicistronic retroviral vector Ha-MDR-IRES-TK allows
      selective killing of MDR1-transduced human tumors transplanted in nude mice.
AB  - Ha-MDR-IRES-TK is a bicistronic vector that coexpresses the MDR1 gene and the
      herpes simplex virus thymidine kinase (HSV-TK) gene. In the present study we
      examined the effect of ganciclovir on MDR1-positive tumors that have been
      transduced with Ha-MDR-IRES-TK. To establish a human tumor xenograft model of
      MDR1-transduced recurrent tumors, human KB-3-1 carcinoma cells were transduced
      with HaMDR or Ha-MDR-IRES-TK, and one each of representative clones, termed
      KB/MDR and KB/MDR-TK, respectively, were isolated. KB/MDR and KB/MDR-TK showed
      similar levels of multidrug resistance in vitro. Vinblastine strongly inhibited
      the growth of the parental KB-3-1 tumors in nude mice but showed little or no
      effect against KB/MDR-TK tumors. Ganciclovir inhibited the in vivo growth of
      KB/MDR-TK tumors almost completely under conditions that did not affect the
      growth of KB-3-1 tumors. Coadministration of vinblastine and ganciclovir
      inhibited the in vivo growth of KB/MDR-TK premixed with KB-3-1 at any ratio. Long
      term, high-level expression of human P-glycoprotein was observed in peripheral
      blood cells of mice transplanted with Ha-MDR-IRES-TK-transduced bone marrow
      cells. Ganciclovir eliminated the P-glycoprotein-positive normal blood cells.
      However, no systemic toxicity was observed. These results clearly demonstrate
      that it is possible to use ganciclovir to treat MDR1-positive tumors that have
      been unintentionally transduced with Ha-MDR-IRES-TK. This safety-modified vector
      should be useful for introducing the MDR1 gene into bone marrow cells to protect
      normal cells from the toxic effects of cancer chemotherapy.

PMID- 9012452
TI  - Differential transfection efficiency rates of the GM-CSF gene into human renal
      cell carcinoma lines by lipofection.
AB  - One of the major questions in any gene therapy approach is the selection of the
      appropriate vector system. Here, the optimization of a gene transfer protocol for
      renal cell carcinoma using lipofection as a nonviral gene transduction system was
      evaluated. To select the promoter which gives the highest expression, different
      plasmids which are able to express Escherichia coli beta-galactosidase gene as a
      reporter gene under the control of different promoters were tested: human
      cytomegalovirus promoter (pCMVbeta), simian virus 40 promoter (pSVbeta),
      adenovirus promoter (ADbeta), and herpes simplex virus thymidine kinase promoter
      (TKbeta). The pCMVbeta revealed the highest expression of the beta-gal gene in
      the renal cell carcinoma (RCC) lines. Thus this CMV promoter was selected for the
      expression of the granulocyte-macrophage colony stimulator factor (GM-CSF) gene.
      Three different lipids (LipofectAmine, LipofectAce, and Lipofectin) were compared
      for their transduction efficiency, and the optimal conditions for quantitatively
      high lipofection rates were established. The consistently best results regarding
      gene expression as well as viability of the RCC lines were obtained when
      Lipofectin was used. Gene expression was monitored by a specific enzyme-linked
      immunosorbent assay and functionally validated by a cell proliferation test. The
      GM-CSF expression profile showed a peak at 48 hours after transfection and was
      still detectable after 5 days. Here the feasibility of efficient lipofection of
      the GM-CSF gene into RCC lines is demonstrated. Most importantly, considerable
      differences in the relative quantity of GM-CSF gene transfer into the different
      RCC lines was observed here. This may be of critical relevance for the design of
      any clinical gene transduction protocol in tumor cell vaccination attempts.

PMID- 9012454
TI  - Clonality of dysplastic epithelium in colorectal adenomas from familial
      adenomatous polyposis patients.
AB  - Loss of function of both alleles of the APC gene results in colorectal adenoma
      formation in familial adenomatous polyposis, an autosomal dominant genetic
      disorder leading to multiple colorectal tumors at an early age. Previous
      molecular studies indicate that the mutant cells forming dysplastic epithelium
      within adenomas are clonally derived. We show, using immunostaining and molecular
      techniques, that the dysplastic epithelium of adenomas actually contains a
      mixture of cells derived from both mutant and normal stem cells. Well
      differentiated mucous cells in the dysplastic epithelium, one of the indicators
      of severity of dysplasia, were derived from normal stem cells. Carcinomas in
      these patients, in contrast, contained only mutant cells, indicating that the
      subsequent mutations incurred by these cells have led to their isolation from the
      normal population.

PMID- 9012453
TI  - Rb functions to inhibit apoptosis during myocyte differentiation.
AB  - During in vitro myogenesis, a portion of myoblasts undergo apoptosis, whereas
      others continue with their differentiation program and form myotubes that are
      resistant to cell death. Previous work has shown that the expression of the Cdk
      inhibitor p21 correlates with enhanced resistance to apoptosis and that forced
      expression of p21 will confer this phenotype on differentiating myocytes. Here we
      examine the role of the retinoblastoma gene (Rb) in myocyte survival. Compared
      with wild-type myocytes, CC42 (Rb-/-) myocytes undergo higher frequencies of
      apoptosis during mitogen deprivation-induced myogenesis. Despite these features,
      Rb-/- myocytes display normal up-regulation of p21 and down-regulation of Cdk
      activities upon differentiation. Adenoviral constructs expressing the Cdk
      inhibitors p21 or p16 inhibit apoptosis in wild-type but not Rb-/- myocyte
      cultures. On the other hand, a Rb-expressing adenoviral construct inhibited
      apoptosis in both cell types. These data demonstrate that Rb functions downstream
      from the Cdk inhibitors to coordinate cell cycle withdrawal with programmed cell
      death during myocyte differentiation.

PMID- 9012455
TI  - Activated N-ras contributes to the chemoresistance of human melanoma in severe
      combined immunodeficiency (SCID) mice by blocking apoptosis.
AB  - Activation of the N-ras gene by point mutations occurs in about 15 % of all human
      melanomas. Using recently established melanoma severe combined immunodeficiency
      human mouse xenotransplantation models, here we further investigate the
      biological significance of these mutations. We demonstrate that activated N-ras
      significantly contributes to the chemoresistance of human melanoma both in vitro
      and in vivo by blocking apoptosis. Overexpression of wild-type N-ras had no such
      effects. With antisense oligonucleotides and farnesyltransferase inhibitors,
      tools capable of blocking Ras function on the therapeutic horizon, our
      observation that activated N-ras is not a bystander but a factor worth targeting
      to improve therapeutic outcome in melanoma gains additional importance.

PMID- 9012456
TI  - Nitrosated glycine derivatives as a potential source of O6-methylguanine in DNA.
AB  - The nitrosated bile acid conjugate N-nitrosoglycocholic acid reacts with DNA to
      give, rise to several adducts including O6-carboxymethylguanine and,
      unexpectedly, O6-methylguanine (O6-MG). O6-MG is well established as a toxic and
      promutagenic lesion and is a substrate for the DNA repair protein O6-alkylguanine
      DNA-alkyltransferase. In contrast, O6-carboxymethylguanine is not repaired by
      this protein. Similar results have been obtained for other nitrosated glycine
      derivatives, which suggests that O6-MG, which has been observed in DNA from human
      gastrointestinal tissues, may be derived from intragastric nitrosation of glycine
      or related compounds.

PMID- 9012457
TI  - Evidence for UV-associated activation of telomerase in human skin.
AB  - Telomerase activation plays a crucial role in the immortalization of human cells
      and carcinogenesis; however, the temporal and pathophysiological aspects of the
      activation in vivo are poorly understood. We found telomerase activity not only
      in malignant tumors (91%) but also in most benign (60%) and premalignant (89%)
      skin tumors. This suggests the involvement of telomerase activation in a crucial
      biological step of human skin carcinogenesis. Because UV light is a major factor
      in skin carcinogenesis, we further examined telomerase activity in normal skin
      samples and in normal skin samples adjacent to benign, premalignant, and
      malignant skin lesions. Data for chronically sun-exposed body sites were compared
      with those for covered sites. Among normal skin samples, 39% (26 of 67) had
      telomerase activity, and this activity was unrelated to neighboring lesions but
      strongly associated with the level of sun exposure. Fifty-four % (21 of 39) of
      normal skin samples from chronically sun-exposed sites were telomerase-positive,
      compared with only 12% (3 of 26) of samples from covered sites. When we examined
      telomerase activity and CC to TT mutations at codons 247/8 of the p53 gene (which
      are considered to be UV specific) in the same normal skin samples, only 43% (7 of
      16) of telomerase-positive normal skin samples at sun-exposed sites contained the
      p53 mutations, whereas all (7 of 7) of the samples with UV-specific p53 mutations
      showed telomerase activity (P = 0.019). These data suggest that telomerase
      activation is involved at an early stage of human skin carcinogenesis and that
      activation may precede the acquisition of UV-associated p53 mutations in the
      skin. Telomerase activity was also found in plucked hair follicles and
      enzymatically separated epidermis, which may be associated with the presence of
      stem cells in the skin.

PMID- 9012458
TI  - Connexin 37 mutations in rat hepatic angiosarcomas induced by vinyl chloride.
AB  - Connexin genes have been shown to restore normal cell growth when transfected
      into certain tumorigenic cells and thus are considered to form a family of tumor
      suppressor genes. In this study, we have analyzed mutations of the connexin 37
      (Cx37) gene in rat hepatic angiosarcomas induced by vinyl chloride. A total of 25
      rat liver tumors (22 hepatic angiosarcomas and 3 hepatocellular carcinomas) were
      analyzed by PCR-single-strand conformation polymorphism analysis and DNA
      sequencing. Four mutations were detected in three tumors: (a) one GGG(Gly) to
      GAG(Glu) mutation at codon 168; and (b) three silent mutations, CGA(Arg) to
      CGC(Arg), at codon 166. In addition, we found that codon 88 is polymorphic
      (GAG(Glu) to GAA(Glu)). Cx37 proteins are detectable in endothelial cells of
      normal liver by immunohistochemical analysis, but none of the angiosarcomas
      showed Cx37-positive spots. These results suggest that Cx37-mediated gap
      junctional intercellular communication may be disturbed in most of these
      angiosarcomas, but mutation of the Cx37 gene is rare.

PMID- 9012459
TI  - Tamoxifen down-regulates CD36 messenger RNA levels in normal and neoplastic human
      breast tissues.
AB  - Tamoxifen (TAM) exerts a long-term suppressive effect on human breast cancer cell
      proliferation. To determine whether the effects of TAM are mediated by specific
      gene activation or repression, normal and tumoral human breast tissues obtained
      before and during TAM treatment were analyzed by differential display technique.
      Total RNA for differential display analysis was obtained from breast tissues from
      two women with the diagnosis of estrogen receptor-positive stage II (T2N1M0)
      infiltrating ductal carcinoma, made by incisional biopsy, followed by modified
      radical mastectomy performed after a 30-day treatment with TAM (20 mg/day). One
      202-bp cDNA band, AP5-1, was present in normal and tumoral biopsy samples, but
      was absent in breast tissue obtained during TAM treatment, and was confirmed by
      Northern hybridization, which showed a 2.7-kb band in both patients. The
      differentially expressed cDNA fragment showed 99% homology to Homo sapiens CD36
      gene, a glycoprotein that acts as a receptor for the extracellular matrix
      proteins thrombospondin-1, collagen types I and IV, and oxidized low-density
      lipoprotein. These results indicate that the down-regulation of CD36 induced by
      TAM might represent alternative or additional mechanisms of action of this drug
      affecting the functions of thrombospondin-1, which is involved in hematogenous
      tumor spread, invasion and angiogenesis, and oxidized low-density lipoprotein,
      playing a role in inhibition of arteriosclerosis. The multiple functions affected
      by the down-regulation of CD36 by TAM warrant the need for additional studies.

PMID- 9012460
TI  - Loss of DCC expression and glioma progression.
AB  - The deleted in colorectal cancer (DCC) gene, a candidate tumor suppressor gene on
      chromosome 18q21, encodes a neural cell adhesion molecule family protein that is
      most highly expressed in the nervous system. To address the hypothesis that DCC
      may play a role in glioma development and/or progression, we examined DCC
      expression by immunohistochemistry in 57 resected human astrocytic tumors.
      Overall, low-grade astrocytomas were predominantly DCC positive (15 of 16, or
      94%), whereas high-grade tumors significantly less often expressed the DCC
      protein (27 of 41, or 66%; P = 0.03). We were able to directly assess the
      relationship between DCC expression and tumor progression in 15 patients who
      initially presented with a low-grade astrocytoma and subsequently recurred with a
      glioblastoma. Within this panel of paired lesions from the same patient, 14 of 15
      (93%) low-grade tumors expressed the DCC protein, whereas only 7 of 15 (47%)
      corresponding glioblastomas were DCC positive. We also observed that secondary
      glioblastomas resulting from malignant progression of low-grade astrocytomas were
      more often DCC negative (8 of 15, or 53%) compared with primary or de novo
      glioblastomas (6 of 26, or 23%; P = 0.05). These findings implicate DCC
      inactivation in glioma progression and also demonstrate that DCC expression is
      preferentially, but not exclusively, lost in the genetic pathway to secondary
      glioblastoma multiforme.

PMID- 9012461
TI  - A novel 4-cM minimally deleted region on chromosome 11p15.1 associated with high
      grade nonmucinous epithelial ovarian carcinomas.
AB  - Prior cytogenetic and restriction fragment length polymorphism studies have
      demonstrated that allelic deletion of chromosome 11p is common in human invasive
      epithelial ovarian tumors. To construct a highly detailed deletion map of
      chromosome 11p, we used 13 polymorphic microsatellite CA repeat primers to
      identify regions harboring potential tumor suppressor genes. Twenty-three of 48
      samples (48%) of invasive epithelial ovarian cancer showed LOH involving at least
      one locus, consistent with prior studies. None of the five mucinous tumors showed
      allelic deletion at any of the 13 primers, suggesting that loss of heterozygosity
      at chromosome 11p may not be involved in the pathogenesis of mucinous ovarian
      cancer. Two separate minimally deleted regions were identified in nonmucinous
      ovarian cancer. The first is an 11-cM region on chromosome 11pl5.5-15.3 that
      extends from D11S2071 to D11S988 and includes the HRAS locus. The second is a
      novel 4-cM region on 11p15.1, defined by marker D11S1310. Deletion of both
      regions at 11p15.5-15.3 and 11p15.1 is strongly associated with high grade
      nonmucinous epithelial ovarian cancer.

PMID- 9012462
TI  - The different RET-activating capability of mutations of cysteine 620 or cysteine
      634 correlates with the multiple endocrine neoplasia type 2 disease phenotype.
AB  - Distinct point mutations of RET, a tyrosine-kinase receptor encoding gene, are
      responsible for the inheritance of multiple endocrine neoplasia type 2 syndromes
      (MEN2A and MEN2B) and familial medullary thyroid carcinoma (FMTC). In particular,
      MEN2A is a more complex and aggressive disease than FMTC, being characterized by
      pheochromocytomas and parathyroid alterations, in addition to medullary thyroid
      carcinomas. The mutations associated with MEN2A and FMTC affect one of five
      cysteine residues mapping in the extracellular domain of the Ret protein.
      However, recent studies have indicated that MEN2A and FMTC disease phenotypes
      correlate with the position of mutations in RET. Mutations of Cys-634 are more
      frequent in families with MEN2A, whereas Cys-620 mutations are very rarely found
      in MEN2A patients and, in contrast, are frequently found in FMTC patients. We
      have reported previously that mutations of Cys-634 constitutively activate the
      RET transforming potential by causing a disulfide bridge-mediated
      homodimerization. Here, we report that the mutation Cys-620 --> Tyr is able to
      cause a constitutive dimerization of Ret, with consequent activation of its
      kinase and transforming activities, to a lower extent than mutation of Cys-634.
      We suggest that the difference in ability to activate RET shown by mutations
      associated with FMTC and MEN2A represents the molecular basis of the phenotypic
      diversity between the two syndromes.

PMID- 9012463
TI  - Thrombospondin-1 and -2 messenger RNA expression in normal, benign, and
      neoplastic human breast tissues: correlation with prognostic factors, tumor
      angiogenesis, and fibroblastic desmoplasia.
AB  - Thrombospondin-1 (TSP1) is a Mr 450,000 extracellular matrix glycoprotein that
      modulates tumor growth, angiogenesis, and metastasis. Of the five structurally
      different TSPs described to date, only TSP2 is similar to TSP1 in terms of its
      molecular architecture, and TSP2 also modulates angiogenesis. Angiogenesis plays
      a relevant role in the biological aggressiveness of breast cancer, and TSP1 is
      present in the tumor stroma (termed desmoplasia) of invasive human breast ductal
      carcinoma not otherwise specified (NOS). The present study was designed to
      identify and quantify TSP1 and TSP2 mRNAs in normal, benign, and neoplastic human
      breast tissues using the reverse transcriptase PCR technique. We found that TSP2,
      like TSP1, was expressed in human breast tissues, and that TSP1 and TSP2 mRNA
      expression in invasive breast carcinoma NOS was significantly increased compared
      to that observed in normal and benign tissues. The expression of TSP1 and TSP2 in
      invasive breast ductal carcinoma NOS did not significantly correlate with any of
      the prognostic factors studied (tumor size, lymph node status, morphology, and
      hormone receptor status). However, when our study population was divided
      according to the quantity of tumor stroma, TSP1 (and possibly TSP2) mRNA
      expression and microvessel counts in desmoplastic-rich stroma of breast carcinoma
      NOS were significantly increased compared to those observed in desmoplastic-poor
      stromata.

PMID- 9012464
TI  - Identification of three distinct tumor suppressor loci on the short arm of
      chromosome 9 in small cell lung cancer.
AB  - Deletion at 9p21 is frequent in many tumor types. A candidate tumor suppressor
      gene, p16INK4a, was mapped to this region and is frequently inactivated by
      several different mechanisms in many tumor types, including non-small cell lung
      cancer, but not in small cell lung cancer (SCLC). p16 functions as a cyclin/CDK
      inhibitor to prevent phosphorylation of pRB. It has been demonstrated that most
      SCLCs have lost pRB but retained p16, and the inactivation of pRB excludes the
      inactivation of p16 and vice versa. To determine the potential existence of other
      tumor suppressor genes on the short arm of chromosome 9 in SCLC, we tested 46
      primary SCLCs by microsatellite analysis. We found that more than 89% of the
      tumors exhibited loss of heterozygosity (LOH) at 9p with three distinct minimal
      deleted areas. Among those areas, LOH at 9p21 was most frequent (86%), with a
      peak at a marker 150 kb telomeric to p16INK4a. LOH was also observed in more than
      50% of the tumors at two other regions, 9p22 and 9p13. Our data strongly suggest
      the presence of at least three novel tumor suppressor loci on 9p in SCLC, and
      further investigations to clone candidate tumor suppressor genes are warranted.

PMID- 9012465
TI  - The reciprocal translocation t(9;16)(q22;p13) is a primary chromosome abnormality
      in basal cell carcinomas.
AB  - The reciprocal translocation t(9;16)(q22;p13) was identified in three short-term
      cultured basal cell carcinomas (BCCs). The t(9;16) was the sole anomaly in one
      clone in two tumors and was accompanied by a second change that also affected the
      long arm of chromosome 9 in the third. In addition, other cytogenetically
      unrelated abnormal clones were also found in all three BCCs. The identification
      of t(9;16)(q22;p13) as a primary chromosomal abnormality in a subset of BCCs (we
      found it in 3 of 22 tumors) is especially intriguing against the background that
      the PTCH gene, which when mutated in the germ line presumably gives rise to the
      autosomal dominant basal cell nevus or Gorlin's syndrome, maps to chromosome band
      9q22. None of the genes rearranged in the BCC-specific t(9;16)(q22;p13)
      translocation have been identified, but we hypothesize that the translocation
      represents the cytogenetic corollary of a tumorigenic recombination of PTCH with
      an as yet unknown gene in 16p13. If so, this would be the first time that a tumor
      suppressor gene causally involved in a hereditary cancer is shown to be
      frequently rearranged through a specific translocation in sporadic carcinomas of
      the same type.

PMID- 9012466
TI  - Evidence that mobile lipids detected in rat brain glioma by 1H nuclear magnetic
      resonance correspond to lipid droplets.
AB  - Mobile lipids have been detected by proton nuclear magnetic resonance (NMR) in
      animal and human tumors (cultured cells, biopsies, and in vivo), but their origin
      and subcellular location are still unclear. They have been associated with
      malignancy, metastatic ability, drug resistance, and necrosis. We wanted to
      determine whether these lipids are located within plasma membrane microdomains or
      in lipid droplets for a C6 cell-induced rat glioma. NMR-visible mobile lipids
      were found in all subcellular fractions isolated from the rat tumor, except in
      the cytosolic supernatants. Transmission electron microscopy showed that lipid
      droplets were present in all subcellular fractions containing NMR-visible lipids
      and in the necrotic and perinecrotic areas of the tumor. The mean diameter of
      droplets isolated by flotation in the subcellular fractionation protocol was 0.97
      microm (n = 682; droplet profile diameter range between 0.2 and 5.0 microm). The
      apparent diffusion coefficient for these lipids (46 +/- 17 microm2 s(-1) measured
      in vivo by proton spectroscopy was four orders of magnitude higher than would be
      expected if mobile lipids were inside plasma membrane microdomains. The combined
      results demonstrated that mobile lipids detected in vivo by proton NMR in the C6
      rat glioma are located in large lipid droplets, associated with the necrotic
      process.

PMID- 9012467
TI  - Metabolic activation of benzo[g]chrysene in the human mammary carcinoma cell line
      MCF-7.
AB  - Benzo[g]chrysene (BgC) is an environmental pollutant, and recent studies have
      demonstrated that anti- BgC-11,12-dihydrodiol 13,14-epoxide (anti-BgCDE) is a
      potent mammary carcinogen in rats. To determine whether BgC can be metabolically
      activated to anti-BgCDE in human cells, the human mammary carcinoma cell line MCF
      7 was treated with BgC and with the racemic trans-3,4- and 11,12-dihydrodiols.
      The DNA adducts formed in these experiments were examined using 32P-postlabeling,
      and specific adducts were identified through comparisons with adducts obtained by
      the reaction of the racemic syn- and anti-BgCDEs with calf thymus DNA and with
      purine deoxyribonucleoside-3'-phosphates in vitro. It was found that BgC is
      metabolically activated in MCF-7 cells to form major DNA adducts through both the
      syn- and anti-11,12-dihydrodiol 13,14-epoxide metabolites. BgC is therefore a
      potential environmental risk to humans. The major BgC-DNA adducts formed from
      both the dihydrodiol-epoxide diastereomers were deoxyadenosine adducts. Thus, BgC
      has DNA-binding properties that are very similar to those of the potent mammary
      carcinogens 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene.

PMID- 9012468
TI  - Chemoprevention of colon carcinogenesis by dietary perillyl alcohol.
AB  - Epidemiological studies suggest that consumption of diets containing fruits and
      vegetables, major sources of phytochemicals and micronutrients, may reduce the
      risk of developing cancer of the colon. Several phytochemicals and micronutrients
      present in fruits and vegetables are known to exert cancer-chemopreventive
      effects in several organs, including the colon. Monoterpenes such as d-limonene
      and perillyl alcohol derived from orange peels and lavender, respectively, have
      been shown to possess chemopreventive properties against mammary, liver, and/or
      lung carcinogenesis. The present study was designed to investigate the efficacy
      of dietary 40 and 80% maximum tolerated dose (MTD) levels of perillyl alcohol on
      azoxymethane (AOM)-induced colon carcinogenesis. The effect of this agent on the
      process of apoptosis in colon tumors was also investigated. Prior to the efficacy
      study, the MTD of perillyl alcohol was determined in male F344 rats in a 6-week
      subchronic toxicity study and found to be a 2.5-g/kg diet when added to the AIN
      76A diet. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A)
      diet or diets containing 1 and 2 g perillyl alcohol/kg diet, representing 40 and
      80% MTD levels, respectively. At 7 weeks of age, all animals except those in the
      vehicle-treated groups were given two weekly s.c. injections of AOM (15 mg/kg
      body weight/week). All animals were continued on their respective dietary regimen
      for 52 weeks after AOM treatment and then sacrificed. Colon tumors were evaluated
      histopathologically using routine procedures. Perillyl alcohol at the 1-g/kg
      level significantly inhibited the incidence (percentage of animals with tumors)
      and multiplicity (tumors/ animals) of invasive adenocarcinomas of the colon,
      whereas perillyl alcohol at 2 g/kg diet inhibited the incidence of total
      adenocarcinomas of the colon and small intestine as compared to the control diet.
      Our studies also indicate that the colon tumors of animals fed perillyl alcohol
      exhibited increased apoptosis as compared to those fed the control diet. These
      results demonstrate the potential chemopreventive activity of perillyl alcohol
      against colon carcinogenesis. The chemopreventive activity of perillyl alcohol is
      mediated through the tumor cell loss by apoptosis.

PMID- 9012469
TI  - Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular
      carcinomas.
AB  - Inactivation of the tumor suppressor p53 seems to be important to the
      pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis
      B virus infection. Although this inactivation may be due to mutations in the p53
      gene, recent evidence suggests that the hepatitis B virus-encoded X antigen
      (HBxAg) binds to and inactivates wild-type p53. Hence, experiments were designed
      to test the hypothesis that there is a low frequency of p53 mutations in HBxAg
      positive HCC. HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and
      nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface
      antigen carriers. HBxAg was detectable in tumor and/or nontumor cells from all
      patients by IHC; six of these samples also had detectable p53. To determine
      whether p53 detection by IHC, and hence stabilization, is associated with
      mutation, sequencing of p53 exons 5-8 was performed with each patient sample.
      Wild-type sequences were found in 13 of 16 HBxAg-positive cases (81%). Hence,
      HBxAg is a common marker of HCC that correlates with the persistence of wild-type
      p53 among both carriers and noncarriers. The low frequency of p53 mutations in
      HCC in these patients implies that p53 inactivation may occur predominantly by
      complex formation with HBxAg.

PMID- 9012470
TI  - Association of immunoreactive hepatocyte growth factor with poor survival in
      resectable non-small cell lung cancer.
AB  - We have shown previously that hepatocyte growth factor (HGF), which is produced
      by lung fibroblasts, is a potent mitogen and motogen for both normal and
      neoplastic bronchial epithelium, and that expression of the HGF receptor, the c
      met proto-oncogene protein, is uniformly found in the human bronchial epithelium
      and in non-small cell lung carcinomas (NSCLCs; P. Singh-Kaw et al., Am. J.
      Physiol., 268: L1012-L1020, 1995). Yamashita et al. have reported an association
      of HGF with poor survival in invasive ductal carcinoma of the breast (Cancer
      Res., 54: 1630-1633, 1994). There are few prognostic markers for lung cancer, and
      the high recurrence rate for stage I lung cancer suggests the frequent presence
      of undetectable tumor burden in such patients. Criteria are needed to evaluate
      these patients for risk of recurrence. We have now evaluated whether HGF present
      in resectable lung tumors has prognostic significance. In this study, 56 primary
      NSCLCs, mainly adenocarcinomas, were examined for presence of HGF by quantitative
      Western blot. These tumors consisted of tissue from 34 stage I patients, 9 stage
      II patients, and 13 stage IIIa patients who underwent curative resection for
      primary NSCLC. Extracts of whole tumor tissue were analyzed after separation of
      proteins by electrophoresis and transfer of proteins to nitrocellulose membranes.
      Immunoreactive (ir)-HGF was visualized by reaction with a polyclonal anti-HGF
      antiserum and quantitated by densitometry. Lung tumor content of ir-HGF varied
      widely among individuals. Median ir-HGF content in tumor extracts was 15.3 ng/40
      microg of tumor protein; mean ir-HGF was 27.2 ng/40 microg of tumor protein. The
      median and mean ir-HGF were both significantly higher in tumor tissue from
      patients who suffered a recurrence during the follow-up period compared with
      those with no evidence or residual disease; this was true of all patients (P =
      0.0001) and stage I patients analyzed separately (P = 0.002). Analysis of
      survival curves indicated that ir-HGF levels higher than the median were
      associated with poor overall survival (P < 0.03). Univariate analysis showed
      three factors related to poor overall survival in this set of patients: ir-HGF,
      tumor (T) status (a measure of primary tumor size and extent), and age. Nodal (N)
      status and stage were only marginally related to overall survival, most likely
      because the majority of the patients in the study were stage I. N status, stage,
      and T status were related to disease-free survival, however. Multivariate Cox
      analysis showed that ir-HGF, T status, and age independently had a negative
      impact on overall survival. ir-HGF was a strong independent negative prognostic
      indicator (P = 0.0001) with a relative risk of 1.022 per unit of ir-HGF (ng/40
      microg of protein). This demonstrates that, in this group of patients, the
      relative risk of ir-HGF content increased continuously as ir-HGF increased, and
      exceeded 10 at units of ir-HGF of 100 or more. In comparison, in this group of
      patients, the relative risk of a T status greater than 1 was 4.75 and that of age
      greater than 65 was 3.95. The combined negative effect of a T status greater than
      1 and elevated ir-HGF on survival was also highly pronounced (P < 0.005). In
      addition, elevated ir-HGF had a negative impact on survival when patients were
      stratified by stage or N status. Stage I patients with high ir-HGF values had a
      worse outcome than stage II or stage IIIa patients with low ir-HGF values.
      Elevated ir-HGF was strongly associated with poor outcome for resectable NSCLC
      patients as a group, and also identified stage I patients with poor outcome,
      indicating that it could be a useful indicator of risk of relapse and death in
      patients who have early lung cancer. The impact of elevated ir-HGF was especially
      prominent in patients whose T status was greater than 1, suggesting that patients
      with both risk factors who are stag

PMID- 9012472
TI  - Radioimmunotherapy and fractionated radiotherapy of human colon cancer liver
      metastases in nude mice.
AB  - Radioimmunotherapy (RIT) and radiotherapy (RT) were evaluated in nude mice
      developing liver metastases of human colon cancer. Without treatment, 90% of
      preconditioned nude mice, injected with LS174T cells intrasplenically and
      splenectomized, died between 26 and 93 days after grafting with few to several
      hundred liver metastases. RIT with 500 microCi of 131I-labeled anti
      carcinoembryonic antigen monoclonal antibodies, injected i.v. in 3 weekly
      fractions, was initiated 1 to 3 weeks after grafting. Mean survival increase was
      43 days for mice treated at 2 weeks. From 13 mice treated at 1 week, 8 mice
      showed long-term survival, a significantly better cure rate compared to RIT at 2
      weeks. Mice undergoing RIT at 3 weeks showed similar survival as untreated
      controls. Mice injected with 131I-labeled irrelevant IgG1 or unlabeled antibody
      showed no significant survival increase. Conventional fractionated external beam
      RT of the liver showed that 40-50 Gy treatment initiated 1 week after grafting
      gave long-term survival in 7 of 13 mice, significantly better compared to RT at 2
      weeks. With combined RIT + RT initiated 2 weeks after grafting, 5 of 11 mice had
      long-term survival in the absence of major toxicities. Thus, early RIT and RT
      were more efficient than later treatments, and combination therapy might give
      further improvement.

PMID- 9012471
TI  - Caffeic acid phenethyl ester stimulates human antioxidant response element
      mediated expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene.
AB  - Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant derived from the
      propolis of honeybee hives. CAPE was shown to inhibit the formation of
      intracellular hydrogen peroxide and oxidized bases in DNA of 12-O
      tetradecanoylphorbol-13-acetate (TPA)-treated HeLa cells and was also found to
      induce a redox change that correlated with differential growth effects in
      transformed cells but not the nontumorigenic parental ones. Mediated via the
      electrophile or human antioxidant response element (hARE), induction of the
      expression of NAD(P)H quinone oxidoreductase (NQO1) and glutathione S-transferase
      Ya subunit genes by certain phenolic antioxidants has been correlated with the
      chemopreventive properties of these agents. Here, we determined by Northern
      analysis that CAPE treatment of hepatoma cells stimulates NQO1 gene expression in
      cultured human hepatoma cells (HepG2), and we characterized the effects of CAPE
      treatment on the expression of a reporter gene either containing or lacking the
      hARE or carrying a mutant version of this element in rodent hepatoma (Hepa-1)
      transfectants. A dose-dependent transactivation of human hARE-mediated
      chloramphenicol acetyltransferase (cat) gene expression was observed upon
      treatments of the Hepa-1 transfectants with TPA, a known inducer, as well as with
      CAPE. The combined treatments resulted in an apparent additive stimulation of the
      reporter expression. To learn whether this activation of cat gene expression was
      effected by protein kinase C in CAPE-treated cells, a comparison was made of cat
      gene activity after addition of calphostin, a protein kinase C inhibitor.
      Calphostin reduced the cat gene induction by TPA but not by CAPE, suggesting that
      stimulation of gene expression in this system by these agents proceeds via
      distinct mechanisms. Band-shift experiments to examine binding of transactivator
      proteins from nuclear extracts of treated and untreated cells to a hARE DNA probe
      showed that TPA exposure increased the binding level. In contrast, binding of
      factors to this probe was inhibited after either in vivo treatment of cells with
      CAPE or in vitro addition of this compound to the nuclear extract. In view of the
      clear stimulation by CAPE of gene expression mediated by hARE, possible
      explanations of this result are discussed.

PMID- 9012473
TI  - High-dose selection with mafosfamide results in sensitivity to DNA cross-linking
      agents: characterization of hypersensitive cell lines.
AB  - One of the most frequently used alkylating drugs in the therapy of a broad
      spectrum of tumors is cyclophosphamide. To elucidate the mechanisms by which
      tumor cells acquire resistance to this agent, Chinese hamster ovary cells (CHO
      K1) were treated with a high dose of the cyclophosphamide analogue mafosfamide,
      and survivors were analyzed as to their cell killing response, chromosomal
      aberrations, and DNA repair capacity. None of the surviving clones tested were
      mafosfamide resistant. Surprisingly, some of the isolated cell lines exhibited a
      mafosfamide-hypersensitive phenotype. Two of these cell variants (designated as
      CHO-K1-4 and CHO-K1-12) were analyzed in more detail and proved to be cross
      sensitive to other DNA cross-linking antineoplastic drugs such as N-hydroxyethyl
      N-chloroethylnitrosourea, treosulfan, melphalan, cisplatin, and mitomycin C. The
      hypersensitivity to the cytotoxic effect of mafosfamide was accompanied by a 2-3
      fold increase in the frequency of chromosomal aberrations. The intracellular
      levels of glutathione and glutathione S-transferase activity of the
      hypersensitive variants as well as growth rate were comparable to wild-type
      cells. Both the variant and the parental cells did not exhibit an increase in the
      amount of p53 upon UV irradiation. Furthermore, sensitive cells displayed similar
      UV-induced unscheduled DNA synthesis and showed identical amounts of ERCC1 mRNA
      as wild-type cells, indicating that the hypersensitive phenotype is not due to a
      defect in nucleotide excision repair. The induction of DNA single-strand breaks
      upon mafosfamide treatment was very similar in wild-type and mutants, and the
      removal of mafosfamide-induced DNA cross-links was not reduced in hypersensitive
      cells. However, the hypersensitive cell variants exhibited a less severe drug
      induced block to DNA replication. From the data obtained, we conclude that
      hypersensitivity to cross-linking agents upon mafosfamide selection is due to
      changes in cell cycle progression of drug-treated cells.

PMID- 9012474
TI  - In vivo gene therapy for alpha-fetoprotein-producing hepatocellular carcinoma by
      adenovirus-mediated transfer of cytosine deaminase gene.
AB  - The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is
      transcriptionally silent in adult liver but overexpressed in human hepatocellular
      carcinoma (HCC). Here, we demonstrate that replication defective recombinant
      adenoviral vectors, containing the human AFP promoter/enhancer, can be used to
      express the Escherichia coli cytosine deaminase (CD) gene (AdAFPCD) and the beta
      galactosidase gene (AdAF-PlacZ) in AFP-producing HCC cell lines. Expression of
      the CD gene by adenovirus from the AFP promoter/enhancer (AdAFPCD) induced cells
      sensitive to 5-fluorocytosine (5FC) in the AFP-producing cells but not in the AFP
      nonproducing cells. Transduction by an adenoviral vector harboring an ubiquitous
      strong promoter and CD gene showed enzymatic activity and 5FC killing in all cell
      lines. When AdAFPlacZ was injected into the s.c. established hepatoma in vivo,
      expression of the beta-galactosidase gene was confined to AFP-producing HCC
      xenografts. Moreover, HCC xenografts regressed by transduction with AdAFPCD and
      subsequently with 5FC treatment in vivo. These findings suggest that utilization
      of the AFP promoter/enhancer in an adenoviral vector can confer selective
      expression of a heterologous suicide gene in hepatocellular carcinoma cells in
      vitro and in vivo.

PMID- 9012475
TI  - Use of a "replication-restricted" herpes virus to treat experimental human
      malignant mesothelioma.
AB  - Modified, nonneurovirulent herpes simplex viruses (HSVs) have shown promise in
      the treatment of brain tumors. However, HSV-1 can infect and lyse a wide range of
      cell types. In this report, we show that HSV-1716, a mutant lacking both copies
      of the gene coding ICP-34.5, can effectively treat a localized i.p. malignancy.
      Human malignant mesothelioma cells supported the growth of HSV-1716 and were
      efficiently lysed in vitro. i.p. injection of HSV-1716 into animals with
      established tumor nodules reduced tumor burden and significantly prolonged
      survival in an animal model of non-central nervous system-localized human
      malignancy without dissemination or persistence after i.p. injection into SCID
      mice bearing human tumors. These findings suggest that this virus may be
      efficacious and safe for use in localized human malignancies of nonneuronal
      origin such as malignant mesothelioma.

PMID- 9012476
TI  - Keratinocyte growth factor ameliorates cyclophosphamide-induced ulcerative
      hemorrhagic cystitis.
AB  - To determine whether keratinocyte growth factor (KGF), an epithelial and
      urothelial growth factor, ameliorates cyclophosphamide (CP)-induced cystitis in
      rats, KGF (5 mg/kg) was injected in rats as a single i.v. injection 24 h prior to
      i.p. injection of CP (200 mg/kg). Bladders were evaluated histologically 48 h
      after CP injection, and KGF pretreatment was found to almost completely prevent
      CP-induced ulcerative hemorrhagic cystitis. Urinary KGF levels were measured by
      ELISA, and KGF was found to be undetectable in control urine, but it was found to
      appear in the urine of KGF-treated rats at 8 h, with a peak concentration of
      approximately 10 ng/ml. Bilateral nephrectomy did not diminish the proliferative
      effect of KGF on urothelium, suggesting that the contribution of urinary KGF to
      urothelial proliferation is insignificant. In conclusion, systemic administration
      of KGF is protective against CP-induced cystitis. Although KGF appears in the
      urine, urinary KGF is not necessary for the proliferative action of KGF on
      urothelium.

PMID- 9012477
TI  - Interleukin (IL)-10, but not IL-4 or IL-13, inhibits cytokine production and
      growth in juvenile myelomonocytic leukemia cells.
AB  - Juvenile myelomonocytic leukemia (JMML) carries a poor prognosis. The endogenous
      production of cytokines by the JMML cells contributes to their growth and
      therapeutic resistance. Interleukin (IL)-4, IL-10, and IL-13 inhibit cytokine
      production in monocytes. We have now studied whether these cytokines can inhibit
      JMML cell cytokine production, thereby potentially reducing the malignant cell
      load in this disorder. We found that IL-10, but not IL-4 or IL-13, dose
      dependently inhibited JMML cell production of the hemopoietic growth factors
      granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha,
      and IL-1beta. Similarly, IL-10, but not IL-4 or IL-13, suppressed JMML colony
      formation and cell viability. This was not due to the absence of receptors
      because we could detect mRNAs for the IL-4 and the IL-13 receptor alpha subunits
      and the IL-2 common gamma subunit in JMML cells. Furthermore, the receptors were
      active since both IL-4 and IL-13 up-regulated surface expression of MHC class II
      and down-regulated CD14 antigens on JMML cells and monocytes. Unlike activated
      monocytes, the JMML cells did not produce IL-10. It is suggested that the loss of
      cytokine inhibitory effects of IL-4 and IL-13 could play a role in the
      pathogenesis of this disorder. On the other hand, the inhibition of cytokine
      production, growth, and viability of JMML cells by IL-10 suggests that this
      cytokine may have a therapeutic potential in JMML.

PMID- 9012478
TI  - Comparison of DNA gains and losses in primary renal clear cell carcinomas and
      metastatic sites: importance of 1q and 3p copy number changes in metastatic
      events.
AB  - Archival material from primary and metastatic renal clear cell carcinomas of 25
      patients was studied by comparative genomic hybridization. Copy number changes of
      entire chromosomes or chromosomal subregions were detected in 22 primary and 21
      metastatic tumors. Copy number changes affected the following chromosomes in at
      least 20% of the 25 primary tumors (minimal common region given in parentheses):
      gains were noted for chromosomes 1 (1q21-->q23), 5 (5q31-->q34), 7 (7p), 8 (8q),
      16 (16p), 17 (17q12-->qter), 19, and 22 (22q12-->qter); losses were revealed for
      chromosomes 3 (3p21-->pter), 8 (8p23-->pter), 14(14q21-->qter), and Y. The same
      chromosomal regions that were involved in primary renal clear cell carcinomas
      were also found in the respective metastatic tumors but with strikingly different
      frequencies for a few regions. Metastatic tumors showed a significantly higher
      frequency of complete or partial gains of the long arm of chromosome 1, in
      particular at 1q21-->q23 than primary tumors (16 cases versus 6 cases; P <
      0.005). These data suggest a correlation of metastatic events in renal clear cell
      carcinomas with an increase in the copy number of genes located at 1q, in
      particular at 1q21-->q23. In contrast, the entire or partial loss of the short
      arm of chromosome 3 was significantly less frequent in metastatic tumors (8 cases
      versus 15 cases; P < 0.025). The validity of 1q and 3p copy number changes
      detected by comparative genomic hybridization was confirmed by interphase
      cytogenetics with region-specific yeast artificial chromosomes to paraffin
      embedded tumor tissue sections.

PMID- 9012479
TI  - Alternative splicing of the APC gene and its association with terminal
      differentiation.
AB  - The human tumor suppressor gene, APC, is composed of at least 21 exons, 7 of
      which are alternatively expressed. Sixteen APC transcripts that differ in their
      5'-most regions and arise by the alternative inclusion of 6 of these exons have
      been identified by reverse transcription-PCR analysis of RNA prepared from human,
      mouse, and rat cell lines and tissues. Tissue-specific differences were observed
      in the expression of APC transcripts without exon 1, a coding region for a heptad
      repeat that supports APC homodimerization. Transcripts without exon 1 were
      observed at high levels in postmitotic, differentiated tissues and in two cell
      lines following the induction of differentiation. Sequence analysis of these
      novel open reading frames predicts APC proteins with different amino-terminal
      domains and therefore potentially different abilities to associate with other
      proteins. Our findings suggest that the alternative splicing of APC leads to
      alternative forms of APC proteins with potentially unique functions in growth
      control and differentiation.

PMID- 9012480
TI  - Identification of a positive regulatory element responsible for tissue-specific
      expression of prostate-specific antigen.
AB  - The prostate-specific antigen (PSA) promoter (PSA-P) has been identified,
      characterized, and determined to be tissue specific. Compared with high
      expression of the genomic PSA gene in prostate cells, expression of the transgene
      driven by the putative PSA promoter is low. This suggests that the identified
      promoter may be incomplete or may function optimally with additional regulatory
      elements. To identify the presence of additional regulatory elements, we screened
      sequences upstream of the PSA promoter and identified a DNA fragment of 822 bp,
      which enhances PSA gene expression. Combining the newly identified PSA gene
      regulatory sequence (PSAR) with our previously identified PSA promoter (PCPSA-P)
      exhibited enhanced expressional activity in the PSA-producing LNCaP cell line.
      With the addition of 10 to 100 nM dihydrotestosterone, a more than 1000-fold
      increase in expression was observed as compared to androgen-negative controls.
      Furthermore, although the combined regulatory element (PSAR)-PSA promoter (PCPSA
      P) sequence resulted in high transgene expression in LNCaP cell lines, the
      combined regulatory element-promoter sequence resulted in minimal expression in
      the non-PSA-producing prostate cell line PC-3, renal tumor cell line R11, and
      cervical adenocarcinoma cell line HeLa. The newly identified 822 bp alone could
      also function as a promoter. Compared with the combined promoter, however, the
      822-bp fragment alone demonstrated lower activity and lower responsiveness to
      androgen stimulation. Our results suggest that coupling the PSA promoter with an
      upstream regulatory element results in a marked increase in PSA expression,
      suggesting that the complete PSA promoter contains two functional domains: a
      proximal promoter and a distal promoter, which can also function as an enhancer.
      The enhanced gene expression of the new construct, combined with its tissue
      specificity and androgen responsiveness, in turn provides a foundation for the
      development of tissue-specific vectors for prostate cancer gene therapy.

PMID- 9012481
TI  - Differential loss of heterozygosity in the region of the Cowden locus within
      10q22-23 in follicular thyroid adenomas and carcinomas.
AB  - The susceptibility gene for Cowden disease (CD), an autosomal dominant inherited
      cancer syndrome, has recently been mapped to an approximately 6-cM interval on
      chromosome subband 10q22-23 between the markers D10S541 and D10S564. CD is
      characterized by hamartomas of many organ systems, including the thyroid, breast,
      skin, and gastrointestinal tract, as well as carcinoma of the thyroid and breast.
      Follicular thyroid adenomas and carcinomas are significant component tumors in
      CD; thus, we sought to examine their sporadic counterpart tumors for loss of
      heterozygosity (LOH) of microsatellite markers in the 20-cM region within and
      flanking the Cowden critical interval. In all, 38 sporadic thyroid tumors were
      analyzed. LOH within the CD interval was observed in 5 of 19 (26%) follicular
      thyroid adenomas and 1 of 9 (11%) Hurthle cell adenomas. Furthermore, of these
      adenomas with LOH, 3 of 4 (75%) were atypical follicular adenomas, whereas 2 of
      15 (13%) were typical follicular adenomas. Surprisingly, no LOH was detected in
      this region in 10 follicular carcinomas. The shortest region of overlap includes
      the markers D10S1735 and D10S1739. If the LOH observed in these sporadic tumors
      is related to the CD gene, then the Cowden critical interval can be revised to
      lie within the interval defined by D10S579 and D10S564. LOH in this narrow
      interval implicates the CD gene, or another gene in that interval, in follicular
      thyroid tumorigenesis. However, this does not explain the lack of LOH in
      follicular carcinomas. Taken together, it may instead be evidence against a
      stepwise progression from atypical adenomas to carcinomas. Alternatively,
      sporadic thyroid adenoma formation may be independent of that locus, but loss of
      this region could prevent carcinoma formation, thus implying that the CD gene may
      be an oncogene or growth promoter.

PMID- 9012482
TI  - Structure and expression of the human FHIT gene in normal and tumor cells.
AB  - The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses
      approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8)
      translocation break at 3p14.2, the FRA3B common fragile region, and homozygous
      deletions in various cancer-derived cell lines. Because some of these genetic
      landmarks (e.g., the t(3;8) break between untranslated FHIT exons 3 and 4, a
      major fragile region that includes a viral integration site between exons 4 and
      5, and cancer cell homozygous deletions in intron 5) do not necessarily affect
      coding exons and yet apparently affect expression of the gene product, we
      examined the FHIT locus and its expression in detail in more than 10 tumor
      derived cell lines to clarify mechanisms underlying aberrant expression. We
      observed some cell lines with apparently continuous large homozygous deletions,
      which included one or more coding exons; cell lines with discontinuous deletions,
      some of which included or excluded coding exons; and cell lines that exhibited
      heterozygous and/or homozygous deletions, by Southern blot analysis for the
      presence of specific exons. Most of the cell lines that exhibited genomic
      alterations showed alteration of FHIT transcripts and absence or diminution of
      Fhit protein.

PMID- 9012483
TI  - Deletion mapping of two potential chromosome 14 tumor suppressor gene loci in
      ovarian carcinoma.
AB  - Previous allelotyping studies of epithelial ovarian carcinoma suggest that loss
      of heterozygosity on chromosome 14q may be a common genetic alteration in this
      tumor type. The purpose of this study was to determine a precise frequency of
      chromosome 14q allelic loss in ovarian carcinomas and to define a minimal
      region(s) of deletion. Seventy-six ovarian carcinomas representative of the
      complete spectrum of grade, stage, and histological subtype were selected for PCR
      based deletion mapping analysis using 15 highly polymorphic microsatellite
      markers spanning the length of this chromosome arm. Loss of heterozygosity was
      observed in 49% of the tumors studied, placing 14q among the most frequently
      affected chromosomal regions in ovarian cancer. Deletions were observed in all
      tumor grades and stages and in all histological subtypes except tumors of low
      malignant potential. Deletion of the entire chromosome arm was rare; the majority
      of tumors displayed partial losses, providing an informative basis for detailed
      deletion mapping. Two distinct minimal regions of deletion were delineated. One
      region was defined by markers D14S80 and D14S75 at 14q12-13, and the other region
      was defined by markers D14S65 and D14S267 at 14q32. These data implicate the
      involvement of two tumor suppressor genes on chromosome 14q in a substantial
      fraction of ovarian carcinomas.

PMID- 9012485
TI  - Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic
      prostatic carcinoma by fluorescence in situ hybridization.
AB  - The role of c-myc in prostatic carcinogenesis is poorly understood. The
      pathogenetic relationship between high-grade prostatic intraepithelial neoplasia
      (PIN), prostatic carcinoma, and metastases is not well-defined. We used
      fluorescence in situ hybridization (FISH) with a region-specific probe for c-myc
      (band 8q24) and chromosome enumeration probes for chromosomes 7, 8, 10, 12, and Y
      to evaluate genetic changes in matched PIN (48 foci), localized prostatic
      carcinoma (71 foci), and lymph node metastases (23 foci) in 25 totally embedded
      whole-mount stage D1 (T2-3 N1-3 M0) radical prostatectomy and pelvic
      lymphadenectomy specimens. The c-myc protein expression in these lesions was
      evaluated by immunohistochemistry. Foci with extra copies of c-myc could be
      divided into three groups: (a) those with simple gain of a whole chromosome 8 (no
      increase in c-myc copy number relative to the chromosome 8 centromere), which was
      identified in 42, 25, and 46% of foci of PIN, carcinoma, and metastases,
      respectively; (b) those with an intermediate increase in c-myc copy number
      relative to the chromosome 8 centromere, which was found in 8, 11, and 25% of
      foci of PIN, carcinoma, and metastases, respectively; and (c) those with
      substantial amplification of c-myc (large increases in c-myc copy number relative
      to the chromosome 8 centromere), which was detected in 0, 8, and 21% of foci of
      PIN, carcinoma, and metastases, respectively. Substantial amplification of c-myc
      was strongly correlated with increasing cancer nuclear grade and
      immunohistochemical evidence of c-myc protein overexpression. Numeric chromosomal
      anomalies were found in 67, 68, and 96% of foci of PIN, carcinoma, and
      metastases, respectively. The most frequent anomaly in PIN and carcinoma was a
      gain of chromosome 8, and the presence of this anomaly strongly correlated with
      Gleason score. Carcinoma foci usually contained more FISH anomalies than paired
      PIN foci, but three prostates contained one or more PIN foci with more anomalies
      than carcinoma. Thirteen primary tumor foci exhibited intratumor genetic
      heterogeneity by FISH. One or more foci of the primary tumor usually shared FISH
      anomalies with the matched metastases. Our FISH results indicate that: (a) gain
      of chromosome 8 and amplification of c-myc are potential markers of prostate
      carcinoma progression; (b) PIN is likely a precursor of carcinoma; (c)
      intraglandular and intratumoral genetic heterogeneity is relatively common; and
      (d) usually a single focus of cancer gives rise to metastases.

PMID- 9012484
TI  - Malignant transformation of nontrophoblastic cells is associated with the
      expression of chorionic gonadotropin beta genes normally transcribed in
      trophoblastic cells.
AB  - The beta subunit of human chorionic gonadotropin (hCGbeta) is encoded by four
      nonallelic CGbeta genes. An assay was developed for distinguishing type I CGbeta
      allelic genes beta7 and beta6, which possess a GCC codon corresponding to an
      alanine at position 117 of hCGbeta, from type II CGbeta genes beta8, beta5, and
      beta3 and its allele beta9, which possess a GAC codon corresponding to an
      aspartic acid at the same position. In normal trophoblast, hCGbeta is encoded by
      type II CGbeta genes, whereas normal nontrophoblastic tissues of differing
      histological origin (breast, prostate, skeletal muscle, bladder, adrenal glands,
      thyroid, colon, and uterus) express only type I CGbeta genes. We studied the
      expression of CGbeta genes in 86 tumor specimens collected from patients with
      breast, bladder, prostate, and thyroid cancer and found that up to 61% of these
      nontrophoblastic tumors expressed type II CGbeta genes. Experiments performed on
      tumor tissues and their normal counterparts confirmed that the malignant
      transformation of nontrophoblastic cells is associated with the expression of
      type II CGbeta genes. These findings provide the basis for a simple test (the
      CG117 assay) that may be useful for the diagnosis of the most frequent
      malignancies.

PMID- 9012486
TI  - TrkA expression decreases the in vivo aggressiveness of C6 glioma cells.
AB  - We stably expressed the nerve growth factor receptor trkA or a truncated trkA
      lacking the kinase domain (trkA delta) in a highly tumorigenic rat glioma cell
      line, C6. Survival of rats with large intrastriatal inocula of C6trkA cells was
      significantly longer than for rats bearing C6 or C6trkA delta cells. Histological
      studies revealed that C6trkA cells were much less invasive than C6 or C6trkA
      delta cells and had a greater rate of apoptosis. There was no apparent induction
      of differentiation of C6 cells by trkA. Therefore, unlike what is observed in
      neuroblastomas, trkA decreases tumorigenicity by modulating invasiveness and
      tumor cell death independent of inducing differentiation. This novel mechanism
      suggests a new therapeutic strategy for malignant gliomas.

PMID- 9012487
TI  - Effects of alterations in calcium homeostasis on apoptosis during neoplastic
      progression.
AB  - Our previous studies showed that early, stage I preneoplastic cells (sup+ I) are
      highly susceptible to apoptosis, whereas the later, stage II preneoplastic cells
      (sup- II) are relatively resistant. To examine possible mechanisms that might
      explain these differences in the regulation of apoptosis, Ca2+ homeostasis was
      analyzed and comparisons were made between these two Syrian hamster embryo cell
      lines. The Ca2+ indicator, fura-2, and fluorescent microscopy were used to
      measure intracellular free calcium concentrations, [Ca2+]i. The results indicated
      that the [Ca2+]i level in logarithmically growing sup+ I cells (approximately 100
      nM) was considerably lower than that observed in sup- II cells (approximately 260
      nM). Serum removal resulted in a reduction of [Ca2+]i in the sup+ I cells
      (approximately 82 nM), whereas the [Ca2+]i level in sup- II cells did not change.
      Endoplasmic reticulum (ER) calcium levels were determined by measuring
      thapsigargin-releasable Ca2+. Reduced ER calcium was consistently observed in
      cells induced to undergo apoptosis. Specifically, thapsigargin-releasable Ca2+
      was greatly reduced in sup+ I cells (45 nM) as compared to sup- II cells (190
      nNM) after 4 h in low serum. When sup- II cells were placed under conditions that
      resulted in apoptosis (thapsigargin or okadaic acid), decreased ER calcium was
      observed. To determine whether reduced ER calcium had a causative effect in
      apoptosis, ER calcium levels were exogenously increased in sup+ I cells by
      raising extracellular Ca2+ to 3 mM; ER calcium levels were maintained, and
      apoptosis was blocked. Studies were performed to determined whether the decrease
      in ER calcium could be attributed to reduced Ca2+ influx at the plasma membrane.
      To measure directly whether Ca2+ entry was decreased in sup+ I cells in 0.2%
      serum, Mn2+ uptake was used to monitor Ca2+ influx. The data show that in low
      serum, the rate of thapsigargin-induced Mn2+ entry in sup+ I cells was
      approximately 50% lower than that of sup- II cells, demonstrating that
      capacitative entry is reduced in sup+ I cells. In further support of this
      hypothesis, thapsigargin-treated sup+ I cells (0.2% serum) showed decreased Ca2+
      entry upon raising extracellular Ca2+ from 0 to 2 mM. We report the novel finding
      that early preneoplastic cells, which exhibit a high propensity to undergo
      apoptosis, have decreased calcium entry at the plasma membrane, resulting in
      decreased ER calcium pools. This study provides new insight into mechanisms that
      can be involved in the regulation/dysregulation of apoptosis during neoplastic
      progression. Furthermore, the data imply that preneoplastic cells, which have
      developed a mechanism to maintain ER calcium, would be less susceptible to
      apoptosis and would thus have an increased potential for becoming transformed.

PMID- 9012489
TI  - Telomerase activity is associated with cell cycle deregulation in human breast
      cancer.
AB  - Deregulation of the cell cycle by abnormal expression of one or several cell
      cycle regulatory proteins is a common finding in malignant tumors and might be a
      prerequisite for cancer development. Telomerase activity is an immortalization
      marker that is found in most cancers and for which an association with an active
      cell cycle has been implicated. In the tissue of 106 human breast carcinomas, we
      analyzed the relationship between telomerase activity levels and defects in the
      cell cycle machinery with a focus on the retinoblastoma protein (pRB) pathway(s).
      The fraction of telomerase-positive tumors was 85%, and large differences in
      telomerase activity were found. Overexpression of cyclin D1 and/or cyclin E, in
      combination with a normal pRB, was a typical feature of tumors with high
      telomerase activity levels. Down-regulation of p16INK4 was not related per se to
      telomerase activity, but tumors with low p16INK4 in combination with cyclin D1 or
      E overexpression demonstrated high activity. Tumor cell proliferation, determined
      by Ki-67 expression, correlated significantly to telomerase activity levels.
      There was, however, not a strict association between proliferation rate and
      telomerase activity, because tumors with inactivated pRB had the highest Ki-67
      fractions but intermediate telomerase activity. Also, cyclin D1 overexpression
      was associated with high telomerase levels without an increase in tumor cell
      proliferation. The present study indicates that telomerase activation occurs
      preferentially in breast cancers with certain cell cycle regulatory defects and
      that telomerase activity levels may depend on the specific defect(s).

PMID- 9012488
TI  - Inhibition of N-linked glycosylation using tunicamycin causes cell death in
      malignant cells: role of down-regulation of the insulin-like growth factor 1
      receptor in induction of apoptosis.
AB  - Recent studies have shown that inhibition of N-linked glycosylation using
      tunicamycin (TM) induces cell death in cultured cells (O. Larsson et al., J. Cell
      Sci., 106: 299-307, 1993; J. Y. Chang and V. Korolev, Exp. Neurol., 137: 201-211,
      1996). The mechanisms underlying TM-induced cell death seem, however, to be
      complex in nature. In SV40-transformed cells, TM triggers within a few minutes
      mechanisms subsequently leading to apoptosis. These mechanisms, although still
      not fully understood, involve an elevation of [Ca2+]i (M. Carlberg et al.,
      Carcinogenesis, 17: 2589-2596, 1996). In contrast, in melanoma cells, TM has to
      be present continuously for 24-48 h to elicit apoptosis. Before the appearance of
      apoptotic melanoma cells, assayed by gel-electrophoretic detection of
      oligonucleosomally fragmented DNA, the binding of insulin-like growth factor I
      (IGF-I) to the cells had become drastically decreased, which in turn was found to
      be due to down-regulation of IGF-I receptor proteins at the cell surface.
      Incubation of the cells with an antibody (alpha IR-3) against the IGF-I-binding
      site of the receptor resulted also in apoptosis, the kinetics of which were
      almost identical to those following treatment with TM. Furthermore, coincubation
      of a high concentration of IGF-I (50 ng/ml) with TM totally rescued the melanoma
      cells from apoptotic cell death during the first 48 h after addition of the
      drugs. This effect was shown to be abolished fully by alpha IR-3. Taken together,
      our data suggest strongly that N-linked glycosylation plays an important role in
      maintenance of viability of melanoma cells through regulating the translocation
      of IGF-I receptor to the cell surface.

PMID- 9012490
TI  - Location and behavior of dorsal determinants during first cell cycle in Xenopus
      eggs.
AB  - In Xenopus eggs, removal of small volumes of cytoplasm along with the surface (2
      10% of the entire egg volume) causes very severe dorsal reduction (average
      DAI=1.4) when made at a site ventrally 30 degrees off the vegetal pole at 20%
      time of first cell cycle (0.2 NT). The greatest dorsal reduction (average
      DAI=1.1) occurs when removal is done at the vegetal pole at 0.3 NT, and
      intermediate reductions (average DAI=2.2-2.6) when done at sites dorsally,
      dorsolaterally or laterally 30 degrees off the vegetal pole at 0.4 NT. Removal at
      sites dorsally, dorsolaterally or laterally 60 degrees off the vegetal pole
      provokes slight dorsal reduction (average DAI=3.5-3.9) when made at 0.4-0.5 NT.
      Removal at all sites after 0.4 NT causes a steady decrease in the extent of
      dorsal reduction. By contrast, removal of larger volumes of dorsal cytoplasm (16
      50% of the entire egg volume) causes a steady increase in the extent of dorsal
      reduction during first cell cycle with its maximum effect at 1.0 NT (average
      DAI=3.1). The surgery for the cytoplasmic removal does not affect cortical
      rotation. We conclude from these results that dorsal determinants are
      concentrated first in a small region ventrally 30 degrees off the vegetal pole by
      0.2 NT, then move toward the vegetal pole during the period 0.2-0.3 NT and
      disperse to a broad region spanning over both the presumptive dorsal and ventral,
      but mainly the dorsal, hemispheres during the period 0.3-0.8 NT.

PMID- 9012491
TI  - Cadherin-mediated cell adhesion and cell motility in Drosophila trachea regulated
      by the transcription factor Escargot.
AB  - Coordination of cell motility and adhesion is essential for concerted movement of
      tissues during animal morphogenesis. The Drosophila tracheal network is formed by
      branching, migration and fusion of tubular ectodermal epithelia. Tracheal tip
      cells, located at the end of each branch that is going to fuse, extend filopodia
      to search for targets and later change their cell shape to a seamless ring to
      allow passage of lumen. The cell adhesion molecule DE-cadherin accumulates at the
      site of contact to form a ring that marks the site of lumen entry and is
      essential for the fusion. DE-cadherin expression in tip cells of a subset of
      branches is dependent on escargot, a zinc finger gene expressed in all tip cells.
      Such escargot mutant tip cells failed to adhere to each other and continued to
      search for alternative targets by extending long filopodia. We present evidence
      indicating escargot positively regulates transcription of the DE-cadherin gene,
      shotgun. Overexpression of DE-cadherin rescued the defect in one of the fusion
      points in escargot mutants, demonstrating an essential role of DE-cadherin in
      target recognition and identifying escargot as a key regulator of cell adhesion
      and motility in tracheal morphogenesis.

PMID- 9012492
TI  - Drosophila brachyenteron regulates gene activity and morphogenesis in the gut.
AB  - Chromosomal region 68D/E is required for various aspects of Drosophila gut
      development; within this region maps the Brachyury homolog T-related gene (Trg),
      DNA of which rescues the hindgut defects of deficiency 68D/E. From a screen of
      13,000 mutagenized chromosomes we identified six non-complementing alleles that
      are lethal over deficiencies of 68D/E and show a hindgut phenotype. These
      mutations constitute an allelic series and are all rescued to viability by a Trg
      transgene. We have named the mutant alleles and the genetic locus they define
      brachyenteron (byn); phenotypic characterization of the strongest alleles allows
      determination of the role of byn in embryogenesis. byn expression is activated by
      tailless, but byn does not regulate itself. byn expression in the hindgut and
      anal pad primordia is required for the regulation of genes encoding transcription
      factors (even-skipped, engrailed, caudal, AbdominalB and orthopedia) and cell
      signaling molecules (wingless and decapentaplegic). In byn mutant embryos, the
      defective program of gene activity in these primordia is followed by apoptosis
      (initiated by reaper expression and completed by macrophage engulfment),
      resulting in severely reduced hindgut and anal pads. Although byn is not
      expressed in the midgut or the Malpighian tubules, it is required for the
      formation of midgut constrictions and for the elongation of the Malpighian
      tubules.

PMID- 9012493
TI  - An indelible lineage marker for Xenopus using a mutated green fluorescent
      protein.
AB  - We describe the use of a DNA construct (named GFP.RN3) encoding green fluorescent
      protein as a lineage marker for Xenopus embryos. This offers the following
      advantages over other lineage markers so far used in Xenopus. When injected as
      synthetic mRNA, its protein emits intense fluorescence in living embryos. It is
      non-toxic, and the fluorescence does not bleach when viewed under 480 nm light.
      It is surprisingly stable, being strongly visible up to the feeding tadpole stage
      (5 days), and in some tissues for several weeks after mRNA injection. We also
      describe a construct that encodes a blue fluorescent protein. We exemplify the
      use of this GFP.RN3 construct for marking the lineage of individual blastomeres
      at the 32- to 64-cell stage, and as a marker for single transplanted blastula
      cells. Both procedures have revealed that the descendants of one embryonic cell
      can contribute single muscle cells to nearly all segmental myotomes rather than
      predominantly to any one myotome. An independent aim of our work has been to
      follow the fate of cells in which an early regulatory gene has been temporarily
      overexpressed. For this purpose, we co-injected GFP.RN3 mRNA and mRNA for the
      early Xenopus gene Eomes, and found that a high concentration of Eomes results in
      ectopic muscle gene activation in only the injected cells. This marker may
      therefore be of general value in providing long term identification of those
      cells in which an early gene with ephemeral expression has been overexpressed.

PMID- 9012494
TI  - BMP-2/-4 mediate programmed cell death in chicken limb buds.
AB  - During limb development, the mesenchymal cells in restricted areas of limb bud,
      anterior necrotic zone, posterior necrotic zone, opaque zone and interdigital
      necrotic zones, are eliminated by programmed cell death. The transcripts of bone
      morphogenetic protein (Bmp)-2 and -4 were first detected in the areas where cell
      death was observed, then showed overlapping expression with the programmed cell
      death zones except the opaque zone. To investigate the function of BMP-2 and BMP
      4 during limb pattern formation, the dominant negative form of BMP receptor was
      overexpressed in chick leg bud via a replication-competent retrovirus to block
      the endogenous BMP-2/-4 signaling pathway. This resulted in excess web formation
      at the anterior and posterior regions of limb buds in addition to marked
      suppression of the regression of webbing at the interdigital regions. Significant
      reductions in the number of apoptotic cells in these three necrotic zones were
      found in the limb buds which received the virus carrying dominant negative BMP
      receptor. This indicates that extra tissue formation is due to suppression of
      programmed cell death in the three necrotic zones. Moreover, BMP-2/-4 protein
      induced apoptosis of mesenchymal cells isolated from the interdigital region in
      vitro. Other TGFbeta family proteins as TGFbeta1 and Activin did not show this
      effect. These results suggest that BMP-2 and BMP-4 are the apoptotic signal
      molecules of the programmed cell death process in the chick limb buds.

PMID- 9012495
TI  - An activated form of type I serine/threonine kinase receptor TARAM-A reveals a
      specific signalling pathway involved in fish head organiser formation.
AB  - The role of Transforming Growth Factor beta (TGF-beta)-related molecules in axis
      formation and mesoderm patterning in vertebrates has been extensively documented,
      but the identity and mechanisms of action of the endogenous molecules remained
      uncertain. In this study, we isolate a novel serine/threonine kinase type I
      receptor, TARAM-A, expressed during early zebrafish embryogenesis first
      ubiquitously and then restricted to dorsal mesoderm during gastrulation. A
      constitutive form of the receptor is able to induce the most anterior dorsal
      mesoderm rapidly and to confer an anterior organizing activity. By contrast, the
      wild-type form is only able to induce a local expansion of the dorsal mesoderm.
      Thus an activated form of TARAM-A is sufficient to induce dorsoanterior
      structures and TARAM-A may be activated by dorsally localized signals. Our data
      suggest the existence in fish of a specific TGF-beta-related pathway for anterior
      dorsal mesoderm induction, possibly mediated by TARAM-A and activated at the late
      blastula stage by localized dorsal determinant.

PMID- 9012496
TI  - Pointed, an ETS domain transcription factor, negatively regulates the EGF
      receptor pathway in Drosophila oogenesis.
AB  - Spatially regulated activation of the Drosophila epidermal growth factor (EGF)
      receptor by its ligand, Gurken, is required for establishment of the
      dorsal/ventral axis of the oocyte and embryo. During mid-oogenesis, Gurken is
      concentrated at the dorsal-anterior of the oocyte and is thought to activate the
      EGF receptor pathway in adjacent follicle cells. In response to this signal,
      dorsal follicle cell fate is determined. These cells further differentiate into
      either appendage-producing or midline cells, resulting in patterning in the
      dorsal follicle cell layer. We show here that Pointed, an ETS transcription
      factor, is required in dorsal follicle cells for this patterning. Loss of pointed
      results in the loss of midline cells and an excess of appendage-forming cells, a
      phenotype associated with overactivation of the EGF receptor pathway in the
      dorsal region. Overexpression of pointed leads to a phenotype similar to that
      generated by loss of the EGF receptor pathway. This suggests that Pointed
      normally down-regulates EGF receptor signaling in the midline to generate
      patterning in the dorsal region. Interestingly, pointed expression is induced by
      the EGF receptor pathway. These data indicate a novel antagonistic function for
      Pointed in oogenesis; in response to activation of the EGF receptor, pointed is
      expressed and negatively regulates the EGF receptor pathway, possibly by
      integrating information from a second pathway.

PMID- 9012497
TI  - Patterning the dorsal longitudinal flight muscles (DLM) of Drosophila: insights
      from the ablation of larval scaffolds.
AB  - The six Dorsal Longitudinal flight Muscles (DLMs) of Drosophila develop from
      three larval muscles that persist into metamorphosis and serve as scaffolds for
      the formation of the adult fibers. We have examined the effect of muscle scaffold
      ablation on the development of DLMs during metamorphosis. Using markers that are
      specific to muscle and myoblasts we show that in response to the ablation,
      myoblasts which would normally fuse with the larval muscle, fuse with each other
      instead, to generate the adult fibers in the appropriate regions of the thorax.
      The development of these de novo DLMs is delayed and is reflected in the delayed
      expression of erect wing, a transcription factor thought to control
      differentiation events associated with myoblast fusion. The newly arising muscles
      express the appropriate adult-specific Actin isoform (88F), indicating that they
      have the correct muscle identity. However, there are frequent errors in the
      number of muscle fibers generated. Ablation of the larval scaffolds for the DLMs
      has revealed an underlying potential of the DLM myoblasts to initiate de novo
      myogenesis in a manner that resembles the mode of formation of the Dorso-Ventral
      Muscles, DVMs, which are the other group of indirect flight muscles. Therefore,
      it appears that the use of larval scaffolds is a superimposition on a commonly
      used mechanism of myogenesis in Drosophila. Our results show that the role of the
      persistent larval muscles in muscle patterning involves the partitioning of DLM
      myoblasts, and in doing so, they regulate formation of the correct number of DLM
      fibers.

PMID- 9012499
TI  - Incomplete sister chromatid separation is the mechanism of programmed chromosome
      elimination during early Sciara coprophila embryogenesis.
AB  - Sex in Sciara coprophila is determined by maternally supplied factors that
      control the number of paternal X chromosomes eliminated during the syncytial
      embryonic divisions. Confocal microscopy and FISH demonstrate that the
      centromeres of the X chromosomes separate at anaphase and remain functional
      during the cycle in which the X chromosomes are eliminated. However, a region of
      the sister chromatids fails to separate and the X chromosomes remain at the
      metaphase plate. This indicates that failure of sister chromatid separation is
      the mechanism of chromosome elimination. Elimination of the X chromosomes
      requires the presence of a previously discovered Controlling Element that acts in
      cis during male meiosis. Using an X-autosome translocation, we demonstrate that
      the Controlling Element acts at-a-distance to prevent sister chromatid separation
      in the arm of an autosome. This indicates that the region in which sister
      chromatid separation fails is chromosome-independent. Although chromosome
      elimination occurs in all somatic nuclei and is independent of location of the
      nuclei within the embryo, the decision to eliminate is made at the level of the
      individual nucleus. Programmed X chromosome elimination occurs at different
      cycles in male and female embryos. These observations support a model in which
      elements on the X chromosome are titrating maternally supplied factors
      controlling the separation of sister X chromatids.

PMID- 9012498
TI  - Notch signaling inhibits muscle cell differentiation through a CBF1-independent
      pathway.
AB  - Notch controls cell fate by inhibiting cellular differentiation, presumably
      through activation of the transcriptional regulator human C promoter Binding
      Factor (CBF1), which transactivates the hairy and Enhancer of split (HES-1) gene.
      However, we describe constitutively active forms of Notch1, which inhibit muscle
      cell differentiation but do not interact with CBF1 or upregulate endogenous HES-1
      expression. In addition, Jagged-Notch interactions that prevent the expression of
      muscle cell specific genes do not involve the upregulation of endogenous HES-1.
      In fact, exogenous expression of HES-1 in C2C12 myoblasts does not block
      myogenesis. Our data demonstrate the existence of a CBF1-independent pathway by
      which Notch inhibits differentiation. We therefore propose that Notch signaling
      activates at least two different pathways: one which involves CBF1 as an
      intermediate and one which does not.

PMID- 9012500
TI  - The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain
      boundary: a study using in situ hybridisation and chick/quail homotopic grafts.
AB  - Segmentation of the neural tube has been clearly shown in the forebrain and
      caudal hindbrain but has never been demonstrated within the midbrain/hindbrain
      domain. Since the homeobox-containing gene Otx2 has a caudal limit of expression
      in this region, we examined, mainly in chick embryos, the possibility that this
      limit could represent an interneuromeric boundary separating either two
      cerebellar domains or the mesencephalic and cerebellar primordia. In situ
      hybridisation with chick or mouse Otx2 probes showed the existence of a transient
      Otx2-negative area in the caudal mesencephalic vesicle, between stages HH10 and
      HH17/18 in chick, and at embryonic day 9.5 in mice. The first post-mitotic
      neurons of the mesencephalon sensu stricto, as labelled with an anti-beta-tubulin
      antibody, overlay the Otx2-positive neuroepithelium with a perfect match of the
      caudal limits of these two markers at all embryonic stages analysed (until stage
      HH20). Chick/quail homotopic grafts of various portions of the midbrain/hindbrain
      domain have shown that the progeny of the cells located in the caudal
      mesencephalic vesicle at stage HH10 are found within the rhombomere 1 as early as
      stage HH14. Furthermore, our results indicate that the cells forming the HH20
      constriction (coinciding with the caudal Otx2 limit) are the progeny of those
      located at the caudal Otx2 limit at stage HH10 (within the mesencephalic
      vesicle). As a result, the Otx2-positive portion of the HH10 mesencephalic
      vesicle gives rise to the HH20 mesencephalon, while the Otx2-negative portion
      gives rise to the HH20 rostral rhombomere 1. Long-survival analysis allowing the
      recognition of the various grisea of the chimeric brains strongly supports the
      view that, as early as stage HH10, the caudal limit of Otx2 expression separates
      mesencephalic from isthmo/cerebellar territories. Finally, this study revealed
      unexpected rostrocaudal morphogenetic movements taking place between stages HH10
      and HH16 in the mediodorsal part of the caudal Otx2-positive domain.

PMID- 9012501
TI  - Temperature-sensitive mutations that arrest Arabidopsis shoot development.
AB  - To identify genes involved in meristem function we have designed a screen for
      temperature-sensitive mutations that cause a conditional arrest of early shoot
      development in Arabidopsis. We describe the characterization of three mutations,
      arrested development (add) 1, 2 and 3. At the restrictive temperature the add1
      and add2 mutations disrupt apical meristem function as assayed by leaf
      initiation. Furthermore, add1 and add2 plants exhibit defects in leaf
      morphogenesis following upshift from permissive to restrictive temperature. This
      result suggests that proximity to a functional meristem is required for the
      completion of normal leaf morphogenesis. The add3 mutation does not have a
      dramatic effect on the production of leaves by the apical meristem; however, add3
      prevents the expansion of leaf blades at high temperature. Thus, in this mutant
      the temperature-dependent arrest of epicotyl development is due to a failure of
      normal leaf development rather than new leaf initiation. While all add mutants
      have a reduced rate of root growth in comparison to wild-type plants, the mutants
      do not display a temperature-dependent arrest of root development. All add
      mutants display some developmental defects at low temperature, suggesting that
      these mutations affect genes involved in inherently temperature-sensitive
      developmental processes.

PMID- 9012502
TI  - Zebrafish tinman homolog demarcates the heart field and initiates myocardial
      differentiation.
AB  - The fashioning of a vertebrate organ requires integration of decisions of cell
      fate by individual cells with those that regulate organotypic form. Logical
      candidates for this role, in an organ such as the heart, are genes that initiate
      the differentiation process leading to heart muscle and those that define the
      earliest embryonic heart field, but for neither class are genes defined. We
      cloned zebrafish Nkx2.5, a homolog of the tinman homeodomain gene needed for
      visceral and cardiac mesoderm formation in Drosophila. In the zebrafish, its
      expression is associated with cardiac precursor cells throughout development,
      even in the early gastrula, where the level of zebrafish Nkx2.5 is in a gradient
      which spatially matches the regional propensity of ventral-marginal cells to
      become heart. Overexpression of Nkx2.5 causes formation of disproportionally
      larger hearts in otherwise apparently normal embryos. Transplanted cell
      expressing high levels of Nkx2.5 express cardiac genes even in ectopic locales.
      Fibroblasts transfected with myc-tagged Nkx2.5 express cardiac genes. These
      effects require the homeodomain. Thus, Nkx2.5 appears to mark the earliest
      embryonic heart field and to be capable of initiating the cardiogenic
      differentiation program. Because ectopic cells or transfected fibroblasts do not
      beat, Nkx2.5 is likely to be but one step in the determination of cardiac myocyte
      cell fate. Its overexpression increases heart size, perhaps by bringing cells on
      the edge of the field to a threshold level for initiation of cardiac
      differentiation.

PMID- 9012503
TI  - Targeted disruption of the Hoxb-2 locus in mice interferes with expression of
      Hoxb-1 and Hoxb-4.
AB  - Mice with a disruption in the hoxb-2 locus were generated by gene targeting. 75%
      of the hoxb-2 mutant homozygotes died within 24 hours of birth. While a majority
      of these mice had severe sternal defects that compromised their ability to
      breathe, some had relatively normal sternum morphology, suggesting that one or
      more additional factor(s) contributed to neonatal lethality. At 3-3.5 weeks of
      age, half of the remaining hoxb-2 homozygotes became weak and subsequently died.
      All of the mutants that survived to 3 weeks of age showed marked facial paralysis
      similar to, but more severe than, that reported for hoxb-1 mutant homozygotes
      (Goddard, J. M., Rossel, M., Manley, N. R. and Capecchi, M. R. (1996) Development
      122, 3217-3228). As for the hoxb-1 mutations, the facial paralysis observed in
      mice homozygous for the hoxb-2 mutation results from a failure to form the
      somatic motor component of the VIIth (facial) nerve which controls the muscles of
      facial expression. Features of this phenotype closely resemble the clinical signs
      associated with Bell's Palsy and Moebius Syndrome in humans. The sternal defects
      seen in hoxb-2 mutant mice are similar to those previously reported for hoxb-4
      mutant mice (Ramirez-Solis, R., Zheng, H., Whiting, J., Krumlauf, R. and Bradley.
      A. (1993) Cell 73, 279-294). The above results suggest that the hoxb-2 mutant
      phenotype may result in part from effects of the hoxb-2 mutation on the
      expression of both hoxb-1 and hoxb-4. Consistent with this proposal, we found
      that the hoxb-2 mutation disrupts the expression of hoxb-1 in cis. In addition,
      the hoxb-2 mutation changes the expression of hoxb-4 and the hoxb-4 mutation, in
      turn, alters the pattern of hoxb-2 expression. Hoxb-2 and hoxb-4 appear to
      function together to mediate proper closure of the ventral thoracic body wall.
      Failure in this closure results in severe defects of the sternum.

PMID- 9012504
TI  - VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in
      lymphatic vascular development.
AB  - The vascular endothelial growth factor family has recently been expanded by the
      isolation of two new VEGF-related factors, VEGF-B and VEGF-C. The physiological
      functions of these factors are largely unknown. Here we report the cloning and
      characterization of mouse VEGF-C, which is produced as a disulfide-linked dimer
      of 415 amino acid residue polypeptides, sharing an 85% identity with the human
      VEGF-C amino acid sequence. The recombinant mouse VEGF-C protein was secreted
      from transfected cells as VEGFR-3 (Flt4) binding polypeptides of 30-32x10(3) Mr
      and 22-23x10(3) Mr which preferentially stimulated the autophosphorylation of
      VEGFR-3 in comparison with VEGFR-2 (KDR). In in situ hybridization, mouse VEGF-C
      mRNA expression was detected in mesenchymal cells of postimplantation mouse
      embryos, particularly in the regions where the lymphatic vessels undergo
      sprouting from embryonic veins, such as the perimetanephric, axillary and jugular
      regions. In addition, the developing mesenterium, which is rich in lymphatic
      vessels, showed strong VEGF-C expression. VEGF-C was also highly expressed in
      adult mouse lung, heart and kidney, where VEGFR-3 was also prominent. The pattern
      of expression of VEGF-C in relation to its major receptor VEGFR-3 during the
      sprouting of the lymphatic endothelium in embryos suggests a paracrine mode of
      action and that one of the functions of VEGF-C may be in the regulation of
      angiogenesis of the lymphatic vasculature.

PMID- 9012505
TI  - Regulation and function of transcription factor GATA-1 during red blood cell
      differentiation.
AB  - The tissue-specific transcription factor GATA-1 is a key regulator of red blood
      cell differentiation. One seemingly contradictory aspect of GATA-1 function is
      that, while it is abundant in erythroid progenitor cells prior to the onset of
      overt differentiation, it does not significantly activate known GATA-1 target
      genes in those cells. To investigate the mechanisms underlying GATA-1 function
      during the transition from early to late erythropoiesis, we have examined its
      expression and activity in normal avian erythroid progenitor cells before and
      after induction of differentiation. In these primary progenitor cells, GATA-1
      protein was predominantly located in the cytoplasm, while induction of
      differentiation caused its rapid relocalization to the nucleus, suggesting that
      nuclear translocation constitutes an important regulatory step in GATA-1
      activation. As an alternative way of addressing the same question, we also
      ectopically expressed a GATA-1/estrogen receptor fusion protein (GATA-1/ER) in
      red blood cell progenitors, where nuclear translocation of, and transcriptional
      activation by, this hybrid factor are conditionally controlled by estrogen. We
      found that hormone-activated GATA-1/ER protein accelerated red blood cell
      differentiation, and concomitantly suppressed cell proliferation. These
      phenotypic effects were accompanied by a simultaneous suppression of c-myb and
      GATA-2 transcription, two genes thought to be involved in the proliferative
      capacity of hematopoietic progenitor cells. Thus, GATA-1 appears to promote
      differentiation in committed erythroid progenitor cells both by inducing
      differentiation-specific genes and by simultaneously suppressing genes involved
      in cell proliferation.

PMID- 9012506
TI  - The chick limbless mutation causes abnormalities in limb bud dorsal-ventral
      patterning: implications for the mechanism of apical ridge formation.
AB  - In chick embryos homozygous for the limbless mutation, limb bud outgrowth is
      initiated, but a morphologically distinct apical ridge does not develop and limbs
      do not form. Here we report the results of an analysis of gene expression in
      limbless mutant limb buds. Fgf4, Fgf8, Bmp2 and Msx2, genes that are expressed in
      the apical ridge of normal limb buds, are not expressed in the mutant limb bud
      ectoderm, providing molecular support for the hypothesis that limb development
      fails in the limbless embryo because of the inability of the ectoderm to form a
      functional ridge. Moreover, Fgf8 expression is not detected in the ectoderm of
      the prospective limb territory or the early limb bud of limbless embryos. Since
      the early stages of limb bud outgrowth occur normally in the mutant embryos, this
      indicates that FGF8 is not required to promote initial limb bud outgrowth. In the
      absence of FGF8, Shh is also not expressed in the mutant limb buds, although its
      expression can be induced by application of FGF8-soaked beads. These observations
      support the hypothesis that Fgf8 is required for the induction of Shh expression
      during normal limb development. Bmp2 expression was also not detected in mutant
      limb mesoderm, consistent with the hypothesis that SHH induces its expression. In
      contrast, SHH is not required for the induction of Hoxd11 or Hoxd13 expression,
      since expression of both these genes was detected in the mutant limb buds. Thus,
      some aspects of mesoderm A-P patterning can occur in the absence of SHH and
      factors normally expressed in the apical ridge. Intriguingly, mutant limbs
      rescued by local application of FGF displayed a dorsalized feather pattern.
      Furthermore, the expression of Wnt7a, Lmx1 and En1, genes involved in limb D-V
      patterning, was found to be abnormal in mutant limb buds. These data suggest that
      D-V patterning and apical ridge formation are linked, since they show that the
      limbless mutation affects both processes. We present a model that explains the
      potential link between D-V positional information and apical ridge formation, and
      discuss the possible function of the limbless gene in terms of this model.

PMID- 9012507
TI  - The neurogenic genes egghead and brainiac define a novel signaling pathway
      essential for epithelial morphogenesis during Drosophila oogenesis.
AB  - Notch (N) and other neurogenic genes have been implicated in two fundamental
      processes, lateral specification of cell fates, and epithelial development.
      Previous studies have suggested that the neurogenic gene brainiac (brn) is
      specifically required for epithelial development (Goode, S., Morgan, M., Liang, Y
      P. and Mahowald, A. P. (1996). Dev. Biol. 178, 35-50). In this report we show
      that egghead (egh), a gene with phenotypes identical to brn, encodes for a novel,
      putative secreted or transmembrane protein. We describe the role of egh and brn
      germline function in the morphogenesis of the follicular epithelium from the time
      it is born through the time that it migrates towards the oocyte late in
      oogenesis. By comparing the function of germline egh and brn to N during
      oogenesis, we have obtained direct evidence for the involvement of Notch in
      maintenance of the follicle cell epithelium, and the specificity of brn and egh
      in epithelial development during oogenesis. The most striking phenotype observed
      for all three genes is a loss of apical-basal polarity and accumulation of
      follicular epithelial cells in multiple layers around the oocyte. The
      spatiotemporal onset of this adenoma-like phenotype correlates with the
      differential accumulation of egh transcripts in the oocyte at stage 4 of
      oogenesis. In contrast to N, we find that brn and egh are essential for the
      organization, but not specification, of stalk and polar cells. The expression
      patterns and functional requirements of brn, egh, and N lead us to propose that
      these genes mediate follicular morphogenesis by regulating germline-follicle cell
      adhesion. This proposal offers explanations for (1) the involvement of egh and
      brn in N-mediated epithelial development, but not lateral specification, (2) why
      brn and egh embryonic neurogenic phenotypes are not as severe as N phenotypes,
      and (3) how egh and brn influence Egfr-mediated processes. The correlation
      between the differential expression of egh in the oocyte and the differential
      requirement for brn, egh, and N in maintaining the follicular epithelium around
      the oocyte, suggests that Egghead is a critical component of a differential
      oocyte-follicle cell adhesive system.

PMID- 9012508
TI  - eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the
      anteroposterior axis in Xenopus.
AB  - Classical embryological experiments suggest that a posterior signal is required
      for patterning the developing anteroposterior axis. In this paper, we investigate
      a potential role for FGF signalling in this process. During normal development,
      embryonic fibroblast growth factor (eFGF) is expressed in the posterior of the
      Xenopus embryo. We have previously shown that overexpression of eFGF from the
      start of gastrulation results in a posteriorised phenotype of reduced head and
      enlarged proctodaeum. We have now determined the molecular basis of this
      phenotype and we propose a role for eFGF in normal anteroposterior patterning. In
      this study, we show that the overexpression of eFGF causes the up-regulation of a
      number of posteriorly expressed genes, and prominent among these are Xcad3, a
      caudal homologue, and the Hox genes, in particular HoxA7. There is both an
      increase of expression within the normal domains and an extension of expression
      towards the anterior. Application of eFGF-loaded beads to specific regions of
      gastrulae reveals that anterior truncations arise from an effect on the
      developing dorsal axis. Similar anterior truncations are caused by the dorsal
      overexpression of Xcad3 or HoxA7. This suggests that this aspect of the eFGF
      overexpression phenotype is caused by the ectopic activation of posterior genes
      in anterior regions. Further results using the dominant negative FGF receptor
      show that the normal expression of posterior Hox genes is dependent on FGF
      signalling and that this regulation is likely mediated by the activation of
      Xcad3. The biological activity of eFGF, together with its expression in the
      posterior of the embryo, make it a good candidate to fulfil the role of the
      'transforming' activity proposed by Nieuwkoop in his 'activation and
      transformation' model for neural patterning.

PMID- 9012509
TI  - Dentate gyrus formation requires Emx2.
AB  - Emx 1 and 2 are the murine homologues of the Drosophila empty spiracles gene and
      based on their expression pattern may be involved in the regional specification
      of the mammalian forebrain. During early embryogenesis, Emx2 is expressed in the
      presumptive cerebral cortex and olfactory bulbs and later, in the hippocampus
      proper and dentate gyrus. The latter are involved in memory processes. To
      understand the role of Emx2 in vivo, we have mutated the gene in mice. Homozygous
      embryos die postnatally because of severe urogenital alterations. These mice
      present cerebral hemispheres with a reduced size and exhibit specific
      morphological alterations in allocortical structures of the medial wall of the
      brain. The dentate gyrus is missing and the hippocampus proper is reduced. The
      medial limbic cortex is also severely shortened. The development of the dentate
      gyrus is affected at the onset of its formation with defects in the
      neuroepithelium from which it originates. These findings demonstrate that Emx2 is
      required for the development of several forebrain structures.

PMID- 9012510
TI  - The distal limb environment regulates MyoD accumulation and muscle
      differentiation in mouse-chick chimaeric limbs.
AB  - Differentiation of muscle and cartilage within developing vertebrate limbs occurs
      in a proximodistal progression. To investigate the cues responsible for
      regulating muscle pattern, mouse myoblasts were implanted into early chick wings
      prior to endogenous chick muscle differentiation. Fetal myogenic cells
      originating from transgenic mice carrying a lacZ reporter were readily detected
      in vivo after implantation and their state of differentiation determined with
      species-specific antibodies to MyoD and myosin heavy chain. When mouse myogenic
      cells are implanted at the growing tip of early stage 21 limbs MyoD expression is
      suppressed and little differentiation of the mouse cells is detected initially.
      At later stages ectopically implanted mouse cells come to lie within muscle
      masses, re-express MyoD and differentiate in parallel with differentiating chick
      myoblasts. However, if mouse cells are implanted either proximally at stage 21 or
      into the limb tip at stage 24, situations in which mouse cells encounter
      endogenous differentiating chick myoblasts earlier, MyoD suppression is not
      detected and a higher proportion of mouse cells differentiate. Mouse cells that
      remain distal to endogenous differentiating myogenic cells are more likely to
      remain undifferentiated than myoblasts that lie within differentiated chick
      muscle. Undifferentiated distal mouse cells are still capable of differentiating
      if explanted in vitro, suggesting that myoblast differentiation is inhibited in
      vivo. In vitro, MyoD is suppressed in primary mouse myoblasts by the addition of
      FGF2 and FGF4 to the culture media. Taken together, our data suggest that the
      inhibition of myogenic differentiation in the distal limb involves MyoD
      suppression in myoblasts, possibly through an FGF-like activity.

PMID- 9012511
TI  - Multiple roles for endothelin in melanocyte development: regulation of progenitor
      number and stimulation of differentiation.
AB  - Melanocytes in the skin are derived from the embryonic neural crest. Recently,
      mutations in endothelin 3 and the endothelin receptor B genes have been shown to
      result in gross pigment defects, indicating that this signalling pathway is
      required for melanocyte development. We have examined the effects of endothelins
      on melanocyte progenitors in cultures of mouse neural crest. Firstly, they
      stimulate an increase in progenitor number and act synergistically with another
      factor, Steel factor, in the survival and proliferation of the progenitors. These
      findings are consistent with findings from mice with natural mutations in the
      endothelin receptor B gene, which show an early loss of melanocyte progenitors.
      Secondly, endothelins induce differentiation of the progenitors into fully mature
      pigmented melanocytes. This finding is consistent with the expression of
      endothelins in the skin of mice at the initiation of pigmentation. The
      melanocytes generated in endothelin-treated cultures also become responsive to
      alpha melanocyte-stimulating hormone, which then acts to regulate the activity of
      the pigmentation pathway. These findings indicate two key roles for endothelin in
      melanocyte development: regulation of expansion of the progenitor pool and
      differentiation of progenitors into mature melanocytes.

PMID- 9012512
TI  - Genetic evidence for the subdivision of the arthropod limb into coxopodite and
      telopodite.
AB  - Arthropod appendages are thought to have evolved as outgrowths from the body wall
      of a limbless ancestor. Snodgrass, in his Principles of Insect Morphology (1935),
      proposed that, during evolution, expansion of the body wall would originate the
      base of the appendages, or coxopodite, upon which the most distal elements that
      represent the true outer limb, or telopodite, would develop. The homeobox gene
      Distal-less (Dll), which is required in the Drosophila appendages for development
      of distal regions, has been proposed to promote formation of telopodite
      structures above the evolutionary ground-state of non-limb or body wall. Here, we
      present evidence that another homeobox gene, extradenticle (exd), which is
      required for appropriate development of the trunk and the proximal parts of the
      appendages, represents a coxopodite gene. We show that exd function is eliminated
      from the distal precursors in the developing limb and remains restricted to
      proximal precursors throughout development. This elimination is important
      because, when ectopically expressed, exd prevents distal development and gives
      rise to truncated appendages lacking distal elements. Moreover, the maintenance
      of exd expression during larval stages, contrary to Dll, does not require the
      hedgehog (hh) signaling pathway, suggesting that the proximal regions of the
      appendages develop independently of hh function. Finally, we show that in the
      crustacean Artemia, exd and Dll are expressed in comparable patterns as in
      Drosophila, suggesting a conserved genetic mechanism subdividing the arthropod
      limb.

PMID- 9012513
TI  - A relationship between apoptosis and flow during programmed capillary regression
      is revealed by vital analysis.
AB  - Previous analyses of developmentally programmed capillary regression suggested
      two distinct causes of vascular endothelial cell (VEC) death. The first appeared
      to be macrophage-dependent (Lang, R. A. and Bishop, M. J. (1993) Cell 74, 453
      462) while the second was proposed to result from cessation of blood flow (Lang,
      R. A., Lustig, M., Francois, F., Sellinger, M. and Plesken, H. (1994).
      Development 120, 3395-3403). Combined, these analyses suggested a model in which
      initial, macrophage-mediated endothelial cell apoptosis blocked blood flow within
      a capillary segment and, as a consequence, caused apoptosis of all remaining
      cells in the affected segment. In the current study, we have tested this model
      using a new method that combines vital and histological analyses as a means of
      determining the fate of whole capillary segments and individual cells in vivo.
      This technique revealed that one of the first events in regression was the
      apoptosis of a single VEC in otherwise normal, flowing capillary segments
      (initiating apoptosis). These isolated, dying VECs projected into and restricted
      the capillary lumen, imposing either a temporary or permanent block to blood
      flow. Following cessation of flow, synchronous apoptosis of VECs occurred
      (secondary apoptosis). In addition, a quantitative analysis revealed a reciprocal
      relationship between plasma flow and VEC apoptosis. These observations are
      consistent with a model for capillary regression in which macrophages induce
      apoptosis in a limited number of VECs and, as a consequence of a block to blood
      flow, also cause apoptosis in those remaining.

PMID- 9012514
TI  - Developmental territories created by mutual antagonism between Wingless and
      Decapentaplegic.
AB  - Drosophila appendages develop from imaginal discs which become subdivided into
      distinct regions during normal patterning. At least 3 axes of asymmetry are
      required to produce a chiral appendage such as a leg. The A/P compartments
      provide one axis of asymmetry in all discs. In leg and antennal discs, the
      anterior compartment becomes asymmetric in the D/V axis with decapentaplegic
      (dpp) expression defining dorsal anterior leg, and wingless (wg) expression
      defining ventral anterior leg. However, unlike wing discs, no D/V compartment has
      been demonstrated in legs or antennae. How are the dorsal anterior and ventral
      anterior territories defined and maintained? Here we show that wg inhibits dpp
      expression and dpp inhibits wg expression in leg and eye/antennal discs. This
      mutual repression provides a mechanism for maintaining separate regions of wg and
      dpp expression in a developing field. We propose the term 'territory' to describe
      regions of cells that are under the domineering influence of a particular
      morphogen. Territories differ from compartments in that they are not defined by
      lineage but are dynamically maintained by continuous morphogen signaling. We
      propose that the anterior compartment of the leg disc is divided into dorsal and
      ventral territories by the mutual antagonism between WG and DPP signaling.

PMID- 9012515
TI  - Nitric oxide-sensitive guanylate cyclase activity is associated with the
      maturational phase of neuronal development in insects.
AB  - Many developing insect neurones pass through a phase when they respond to nitric
      oxide (NO) by producing cyclic GMP. Studies on identified grasshopper
      motoneurones show that this NO sensitivity appears after the growth cone has
      arrived at its target but before it has started to send out branches. NO
      sensitivity typically ends as synaptogenesis is nearing completion. Data from
      interneurones and sensory neurones are also consistent with the hypothesis that
      NO sensitivity appears as a developing neurone changes from axonal outgrowth to
      maturation and synaptogenesis. Cyclic GMP likely constitutes part of a retrograde
      signalling pathway between a neurone and its synaptic partner. NO sensitivity
      also appears in some mature neurones at times when they may be undergoing
      synaptic rearrangement. Comparative studies on other insects indicate that the
      association between an NO-sensitive guanylate cyclase and synaptogenesis is an
      ancient one, as evidenced by its presence in both ancient and more recently
      evolved insect groups.

PMID- 9012516
TI  - alpha-spectrin is required for germline cell division and differentiation in the
      Drosophila ovary.
AB  - During Drosophila oogenesis, developing germline cysts are spanned by a large
      cytoplasmic structure called a fusome, containing alpha-spectrin and the adducin
      like product of the hu-li tai shao (hts) gene. We found that fusomes contain two
      additional membrane skeletal proteins: beta-spectrin and ankyrin. hts was shown
      previously to be required for cyst formation and oocyte differentiation; the role
      of the fusome itself, however, and the organization and function of its other
      components, remains unclear. Using the FRT/FLP recombinase system to generate
      clones of alpha-spectrin-deficient cells in the ovary, we have shown that alpha
      spectrin is also required for cyst formation and oocyte differentiation, but that
      its role in each process is distinct from that of Hts protein. Furthermore, alpha
      spectrin is required for these processes in germline cells, but not in the
      follicle cells that surround each cyst. We have also found that the organization
      of membrane skeletal proteins is more dependent on alpha-spectrin in the fusome
      than at the plasma membrane in other cells. Our results suggest that the fusome
      and its associated membrane skeleton play a central role in regulating the
      divisions and differentiation of cyst cells.

PMID- 9012517
TI  - Joint patterning defects caused by single and double mutations in members of the
      bone morphogenetic protein (BMP) family.
AB  - The mouse brachypodism locus encodes a bone morphogenetic protein (BMP)-like
      molecule called growth/differentiation factor 5 (GDF5). Here we show that Gdf5
      transcripts are expressed in a striking pattern of transverse stripes within many
      skeletal precursors in the developing limb. The number, location and time of
      appearance of these stripes corresponds to the sites where joints will later form
      between skeletal elements. Null mutations in Gdf5 disrupt the formation of more
      than 30% of the synovial joints in the limb, leading to complete or partial
      fusions between particular skeletal elements, and changes in the patterns of
      repeating structures in the digits, wrists and ankles. Mice carrying null
      mutations in both Gdf5 and another BMP family member, Bmp5, show additional
      abnormalities not observed in either of the single mutants. These defects include
      disruption of the sternebrae within the sternum and abnormal formation of the
      fibrocartilaginous joints between the sternebrae and ribs. Previous studies have
      shown that members of the BMP family are required for normal development of
      cartilage and bone. The current studies suggest that particular BMP family
      members may also play an essential role in the segmentation process that cleaves
      skeletal precursors into separate elements. This process helps determine the
      number of elements in repeating series in both limbs and sternum, and is required
      for normal generation of the functional articulations between many adjacent
      structures in the vertebrate skeleton.

PMID- 9012518
TI  - valentino: a zebrafish gene required for normal hindbrain segmentation.
AB  - Mutational analysis can serve both to identify new genes essential for patterning
      embryonic development and to determine their functions. Here we describe the
      identification and phenotypic characterization of alleles of valentino, which we
      recovered in a genetic screen that sought to identify mutations in the zebrafish
      that disrupt region-specific gene expression patterns in the embryonic brain.
      valentino is required for normal hindbrain segmentation and the hindbrain of
      valentino mutant embryos is shortened by the length of one rhombomere. We
      demonstrate that valentino is required cell-autonomously in the development of
      rhombomeres 5 and 6, and propose that valentino functions in the subdivision and
      expansion of a common precursor region in the presumptive hindbrain into the
      definitive rhombomeres 5 and 6. These results provide genetic evidence for a two
      segment periodicity in the hindbrain and suggest that this periodicity arises
      sequentially, through the specification and later subdivision of a two-rhombomere
      unit, or 'protosegment'.

PMID- 9012519
TI  - The human beta-globin locus control region confers an early embryonic erythroid
      specific expression pattern to a basic promoter driving the bacterial lacZ gene.
AB  - The beta-globin locus control region (LCR) is contained on a 20 kb DNA fragment
      and is characterized by the presence of five DNaseI hypersensitive sites in
      erythroid cells, termed 5'HS1-5. A fully active 6.5 kb version of the LCR, called
      the muLCR, has been described. Expression of the beta-like globin genes is
      absolutely dependent on the presence of the LCR. The developmental expression
      pattern of the genes in the cluster is achieved through competition of the
      promoters for the activating function of the LCR. Transgenic mice experiments
      suggest that subtle changes in the transcription factor environment lead to the
      successive silencing of the embryonic epsilon-globin and fetal gamma-globin
      promoters, resulting in the almost exclusive transcription of the beta-globin
      gene in adult erythropoiesis. In this paper, we have asked the question whether
      the LCR and its individual hypersensitive sites 5'HS1-4 can activate a basic
      promoter in the absence of any other globin sequences. We have employed a minimal
      promoter derived from the mouse Hsp68 gene driving the bacterial beta
      galactosidase (lacZ) gene. The results show that the muLCR and 5'HS3 direct
      erythroid-specific, embryonic expression of this construct, while 5'HS1, 5'HS2
      and 5'HS4 are inactive at any stage of development. Expression of the muLCR and
      5'HS3 transgenes is repressed during fetal stages of development. The transgenes
      are in an inactive chromatin conformation and the lacZ gene is not transcribed,
      as shown by in situ hybridization. These data are compatible with the hypothesis
      that the LCR requires the presence of an active promoter to adopt an open
      chromatin conformation and with models proposing progressive heterochromatization
      during embryogenesis. The results suggest that the presence of a beta-globin gene
      is required for LCR function as conditions become more stringent during
      development.

PMID- 9012520
TI  - Expression cloning of a Xenopus T-related gene (Xombi) involved in mesodermal
      patterning and blastopore lip formation.
AB  - We have used a functional assay to identify a putative T-box transcription factor
      (Xombi) that has the ability to induce sites of invagination in the ectoderm of
      Xenopus embryos that resemble the blastopore lip. Maternal Xombi transcript is
      first localized to the oocyte's vegetal cortex and cytoplasm, early sources of
      mesoderm and endoderm-inducing signals. Soon after zygotic transcription begins,
      there is a wave of Xombi expression, beginning in dorsal mesoderm and then
      extending to lateral and ventral mesoderm, that precedes and parallels blastopore
      lip formation at the border between the mesoderm and endoderm. Transcripts
      encoding brachyury, Xwnt8 and goosecoid colocalize with Xombi transcripts within
      the marginal zone; ectopic expression of Xombi induces expression of all three
      mesodermal genes. In ectodermal explants, Xombi expression is induced by the
      secreted mesoderm inducers activinA, activinB, Xnrl and eFGF, and by brachyury,
      another Xenopus T-box containing gene. The time course and location of Xombi
      expression, its biological activities and the partial dependence of Xombi
      expression and blastopore lip formation on fibroblast growth factor (FGF)
      signaling suggest that Xombi contributes to a traveling wave of morphogenesis and
      differentiation during Xenopus gastrulation.

PMID- 9012521
TI  - Apoptosis in the terminal endbud of the murine mammary gland: a mechanism of
      ductal morphogenesis.
AB  - Ductal morphogenesis in the rodent mammary gland is characterized by the rapid
      penetration of the stromal fat pad by the highly proliferative terminal endbud
      and subsequent formation of an arborized pattern of ducts. The role of apoptosis
      in ductal morphogenesis of the murine mammary gland and its potential regulatory
      mechanisms was investigated in this study. Significant apoptosis was observed in
      the body cells of the terminal endbud during the early stage of mammary ductal
      development. Apoptosis occurred predominately in defined zones of the terminal
      endbud; 14.5% of the cells within three cell layers of the lumen were undergoing
      apoptosis compared to 7.9% outside this boundary. Interestingly, DNA synthesis in
      the terminal endbud demonstrated a reciprocal pattern; 21.1% outside three cell
      layers and 13.8% within. Apoptosis was very low in the highly proliferative cap
      cell laver and in regions of active proliferation within the terminal endbud. In
      comparison to other stages of murine mammary gland development, the terminal
      endbud possesses the highest level of programmed cell death observed to date.
      These data suggest that apoptosis is an important mechanism in ductal
      morphogenesis. In p53-deficient mice, the level of apoptosis was reduced, but did
      not manifest a detectable change in ductal morphology, suggesting that p53
      dependent apoptosis is not primarily involved in formation of the duct.
      Immunohistochemical examination of the expression of the apoptotic checkpoint
      proteins, Bcl-x, Bax and Bcl-2, demonstrated that they are expressed in the
      terminal endbud. Bcl-x and Bcl-2 expression is highest in the body cells and
      lowest in the nonapoptotic cap cells, implying that their expression is
      associated with increased apoptotic potential. Bax expression was distributed
      throughout the terminal endbud independent of the observed pattern of apoptosis.
      A functional role for Bcl-2 family members in regulating endbud apoptosis was
      demonstrated by the significantly reduced level of apoptosis observed in WAP-Bcl
      2 transgenic mice. The pattern of apoptosis and ductal structure of endbuds in
      these mice was also disrupted. These data demonstrate that p53-independent
      apoptosis may play a critical role in the early development of the mammary gland.

PMID- 9012522
TI  - A molecular aspect of hematopoiesis and endoderm development common to
      vertebrates and Drosophila.
AB  - In vertebrates, transcriptional regulators of the GATA family appear to have a
      conserved function in differentiation and organ development. GATA-1, -2 and -3
      are required for different aspects of hematopoiesis, while GATA-4, -5 and -6 are
      expressed in various organs of endodermal origin, such as intestine and liver,
      and are implicated in endodermal differentiation. Here we report that the
      Drosophila gene serpent (srp) encodes the previously described GATA factor ABF.
      The multiple functions of srp in Drosophila suggest that it is an ortholog of the
      entire vertebrate Gata family. srp is required for the differentiation and
      morphogenesis of the endodermal gut. Here we show that it is also essential for
      Drosophila hematopoiesis and for the formation of the fat body, the insect organ
      analogous to the liver. These findings imply that some aspects of the molecular
      mechanisms underlying blood cell development as well as endodermal
      differentiation are early acquisitions of metazoan evolution and may be common to
      most higher animals.

PMID- 9012523
TI  - The Drosophila decapentaplegic and short gastrulation genes function
      antagonistically during adult wing vein development.
AB  - TGF-beta-related signaling pathways play diverse roles during vertebrate and
      invertebrate development. A common mechanism for regulating the activity of TGF
      beta family members is inhibition by extracellular antagonists. Recently, the
      Drosophila short gastrulation (sog) gene was shown to encode a predicted
      diffusible factor which antagonizes signaling mediated by the TGF-beta-like
      Decapentaplegic (Dpp) pathway in the early blastoderm embryo. sog and dpp, which
      are among the earliest zygotic genes to be activated, are expressed in
      complementary dorsal-ventral domains. The opposing actions of sog and dpp in the
      early embryo have been highly conserved during evolution as their vertebrate
      counterparts, chordin and BMP-4, function homologously to define neural versus
      non-neural ectoderm in Xenopus. Here we exploit the genetically sensitive adult
      wing vein pattern to investigate the generality of the antagonistic relationship
      between sog and dpp. We show that dpp is expressed in vein primordia during pupal
      wing development and functions to promote vein formation. In contrast, sog is
      expressed in complementary intervein cells and suppresses vein formation. sog and
      dpp function during the same phenocritical periods (i.e. 16-28 hours after
      pupariation) to influence the vein versus intervein cell fate choice. The
      conflicting activities of dpp and sog are also revealed by antagonistic dosage
      sensitive interactions between these two genes during vein development. Analysis
      of vein and intervein marker expression in dpp and sog mutant wings suggests that
      dpp promotes vein fates indirectly by activating the vein gene rhomboid (rho),
      and that sog functions by blocking an autoactivating Dpp feedback loop. These
      data support the view that Sog is a dedicated Dpp antagonist.

PMID- 9012524
TI  - Quantitative functional interrelations within the cis-regulatory system of the S.
      purpuratus Endo16 gene.
AB  - Embryonic expression of the Endo16 gene of Strongylocentrotus purpuratus is
      controlled by interactions with at least 13 different DNA-binding factors. These
      interactions occur within a cis-regulatory domain that extends about 2300 bp
      upstream from the transcription start site. A recent functional characterization
      of this domain reveals six different subregions, or cis-regulatory modules, each
      of which displays a specific regulatory subfunction when linked with the basal
      promoter and in some cases various other modules (C.-H. Yuh and E. Davidson
      (1996) Development 122, 1069-1082). In the present work, we analyzed quantitative
      time-course measurements of the CAT enzyme output of embryos bearing expression
      constructs controlled by various Endo16 regulatory modules, either singly or in
      combination. Three of these modules function positively in that, in isolation,
      each is capable of promoting expression in vegetal plate and adjacent cell
      lineages, though with different temporal profiles of activity. Models for the
      mode of interaction of the three positive modules with one another were tested by
      assuming mathematical relations that would generate, from the measured single
      module time courses, the experimentally observed profiles of activity obtained
      when the relevant modules are physically linked in the same construct. The
      generated and observed time functions were compared, and the differences were
      minimized by least squares adjustment of a scale parameter. When the modules were
      tested in context of the endogenous promoter region, one of the positive modules
      (A) was found to increase the output of the others (B and G), by a constant
      factor. In contrast, a solution in which the time-course data of modules A and B
      are multiplied by one another was required for the interrelations of the positive
      modules when a minimal SV40 promoter was used. One interpretation is that, in
      this construct, each module independently stimulates the basal transcription
      complex. We used a similar approach to analyze the repressive activity of the
      three Endo16 cis-regulatory modules that act negatively in controlling spatial
      expression. The evidence obtained confirms that the repressive modules act only
      by affecting the output of module A (C.-H. Yuh and E. Davidson (1996) Development
      122, 1069-1082). A new hierarchical model of the cis-regulatory system was
      formulated in which module A plays a central integrating role, and which also
      implies specific functions for certain DNA-binding sites within the basal
      promoter fragment of the gene. Additional kinetic experiments were then carried
      out, and key aspects of the model were confirmed.

PMID- 9012525
TI  - Gonadal sex reversal of the developing marsupial ovary in vivo and in vitro.
AB  - Undifferentiated tammar wallaby ovaries were transplanted under the skin of male
      pouch young during the period of mitotic division of the XX germ cells. After 25
      days, all the germ cells had disappeared and the ovaries contained seminiferous
      like cords. Similarly, undifferentiated ovaries cultured for 4 days with
      recombinant human Mullerian-inhibiting substance (rhMIS) also contained well
      differentiated seminiferous-like cords and few or no surviving germ cells. The
      majority of controls cultured without rhMIS developed as normal ovaries. However,
      in a few control ovaries seminiferous-like cords developed in those regions of
      the ovaries that were partially necrotic and contained few germ cells. These
      results strongly suggest that sex-reversal of the tammar ovary is the direct
      result of loss of mitotic germ cells, rather than an effect of MIS on female
      somatic cells. MIS is apparently toxic to these female germ cells in mitosis, but
      not to male germ cells in mitosis. Thus, in normal development in the tammar, the
      presence of XX germ cells in the ovary inhibits the formation of seminiferous
      cords so that the gonad develops as an ovary.

PMID- 9012526
TI  - Somatic sex-determining signals act on XX germ cells in Drosophila embryos.
AB  - In Drosophila, the enhancer-trap line mgm1 is already specifically expressed in
      male germ cells. Staining is first detected in 10-hour-old embryos and it is
      found in later stem cells. This line, which reveals the earliest sex-specific
      gene expression in the germline known so far, is a useful molecular marker to
      assess the sexual pathway that germ cells have entered before any overt sexual
      dimorphism is apparent. XY germ cells that develop in feminized animals express
      mgm1, which shows that this marker is autonomously expressed in XY germ cells.
      However, XX germ cells that develop in masculinized animals also express mgm1.
      Therefore, somatic sex-determining signals have already acted on XX germ cells in
      10-hour-old embryos.

PMID- 9012527
TI  - The Drosophila Enhancer of zeste gene encodes a chromosomal protein: examination
      of wild-type and mutant protein distribution.
AB  - The Drosophila Enhancer of zeste [E(z)] gene is a member of the Polycomb-group
      and, as such, is involved in maintaining the transcriptional repression of the
      homeotic genes of the Antennapedia (ANT-C) and bithorax (BX-C) complexes. It has
      been proposed that Polycomb-group (Pc-G)-mediated silencing requires the
      formation of heteromeric protein complexes which modify the chromatin structure
      of target genes. We describe the in vivo distribution of the E(Z) protein and
      show it to be ubiquitously present in embryonic and larval nuclei. In salivary
      gland polytenized nuclei, the identifiable E(Z) chromosome binding sites are a
      subset of those described for other Polycomb-group proteins, suggesting that E(Z)
      may also participate in Polycomb-group complexes. E(Z) binds to chromosomes in a
      DNA sequence-dependent manner, as illustrated by the creation of a new E(Z)
      binding site at the location of a P element reporter construct that previously
      has been shown to contain a Polycomb response element (PRE). We also present the
      sequences of one null and three temperature-sensitive E(z) alleles, describe the
      effects these mutations have on the in vivo distribution of E(Z) protein and
      discuss their implications concerning putative functional domains. Finally, we
      describe the effect a trithorax mutation has on E(Z) chromosome binding.

PMID- 9012528
TI  - Spinal cord oligodendrocytes develop from ventrally derived progenitor cells that
      express PDGF alpha-receptors.
AB  - Platelet-derived growth factor alpha-receptors (PDGFR alpha) are expressed by a
      subset of neuroepithelial cells in the ventral half of the embryonic day 14 (E14)
      rat spinal cord. The progeny of these cells subsequently proliferate and migrate
      into the dorsal parts of the cord after E16. Here, we show that E14 ventral cells
      are able to generate oligodendrocytes in culture but that dorsal cells acquire
      this ability only after E16, coinciding with the appearance of PDGFR alpha
      immunoreactive cells in the starting population. PDGFR alpha-positive cells in
      optic nerve and spinal cord cultures co-labelled with antibody markers of
      oligodendrocyte progenitors. When PDGFR alpha-positive cells were purified from
      embryonic rat spinal cords by immunoselection and cultured in defined medium,
      they all differentiated into oligodendrocytes. Very few oligodendrocytes
      developed in cultures of embryonic spinal cord cells that had been depleted of
      PDGFR alpha-expressing cells by antibody-mediated complement lysis. These data
      demonstrate that all PDGFR alpha-positive cells in the embryonic rat spinal cord
      are oligodendrocyte progenitors and that most or all early-developing
      oligodendrocytes are derived from these ventrally-derived precursors.

PMID- 9012529
TI  - Compartments, wingless and engrailed: patterning the ventral epidermis of
      Drosophila embryos.
AB  - Recent experiments on the wing disc of Drosophila have shown that cells at the
      interface between the anterior and posterior compartments drive pattern formation
      by becoming the source of a morphogen. Here we ask whether this model applies to
      the ventral embryonic epidermis. First, we show that interfaces between posterior
      (engrailed ON) and anterior (engrailed OFF) cells are required for pattern
      formation. Second, we provide evidence that Wingless could play the role of the
      morphogen, at least within part of the segmental pattern. We looked at the
      cuticular structures that develop after different levels of uniform Wingless
      activity are added back to unsegmented embryos (wingless- engrailed-). Because it
      is rich in landmarks, the T1 segment is a good region to analyse. There, we find
      that the cuticle formed depends on the amount of added Wingless activity. For
      example, a high concentration of Wingless gives the cuticle elements normally
      found near the top of the presumed gradient. Unsegmented embryos are much shorter
      than wild type. If Wingless activity is added in stripes, the embryos are longer
      than if it is added uniformly. We suggest that the Wingless gradient landscape
      affects the size of the embryo, so that steep slopes would allow cells to survive
      and divide, while an even distribution of morphogen would promote cell death.
      Supporting the hypothesis that Wingless acts as a morphogen, we find that these
      stripes affect, at a distance, the type of cuticle formed and the planar polarity
      of the cells.

PMID- 9012530
TI  - lin-12 and glp-1 are required zygotically for early embryonic cellular
      interactions and are regulated by maternal GLP-1 signaling in Caenorhabditis
      elegans.
AB  - Cell-cell interactions mediated by LIN-12 and GLP-1, members of the LNG (LIN-12,
      Notch, GLP-1) family of receptors, are required to specify numerous cell fates
      during development of the nematode Caenorhabditis elegans. Maternally expressed
      GLP-1 participates in two of at least four sequential inductive interactions that
      specify the fates of early embryonic descendants of the AB founder cell. We
      report that GLP-1 and LIN-12, and apparently their ligand, LAG-2, as well as a
      downstream component, LAG-1, are required in the latter two inductions. We find
      that LAG-2 is expressed in the signaling cells and LIN-12 is expressed in cells
      receiving the inductions, consistent with their proposed roles as ligand and
      receptor, respectively. Furthermore, we report that maternal GLP-1 activity is
      required (1) to repress early zygotic lag-2 expression and (2) to activate
      zygotic lin-12 expression in the early embryo. The patterning of both receptor
      and ligand expression by maternal GLP-1 signaling establishes competence for the
      zygotic LNG-mediated cellular interactions and localizes these interactions to
      the appropriate cells. We propose that activation of maternal GLP-1 regulates
      zygotic lin-12 and lag-2 expression by a regulatory mechanism analogous to that
      described for the post-embryonic gonad.

PMID- 9012531
TI  - Xenopus VegT RNA is localized to the vegetal cortex during oogenesis and encodes
      a novel T-box transcription factor involved in mesodermal patterning.
AB  - An RNA localized to the vegetal cortex of Xenopus oocytes encodes a novel T-box
      protein (VegT) capable of inducing either dorsal or posterior ventral mesoderm at
      different times in development. VegT is a nuclear protein and its C-terminal
      domain can activate transcription in a yeast reporter assay, observations
      consistent with VegT functioning as a transcription factor. Zygotic expression is
      dynamic along the dorsoventral axis, with transcripts first expressed in the
      dorsal marginal zone. By the end of gastrulation, VegT is expressed exclusively
      in posterior ventral and lateral mesoderm and is excluded from the notochord.
      Later expression is confined to a subset of Rohon-Beard cells, a type of primary
      sensory neuron. In animal cap assays, VegT is capable of converting prospective
      ectoderm into ventral lateral mesoderm. Such ectopic expression of VegT induces
      its own expression as well as that of Xwnt-8 in caps, suggesting that a Wnt
      pathway may be involved. Mis-expression of VegT in dorsal animal blastomeres
      fated to contribute to brain suppresses head formation. Our results suggest that
      VegT is a localized transcription factor, which operates sequentially in several
      developmental pathways during embryogenesis, including dorsoventral and posterior
      patterning of mesoderm.

PMID- 9012532
TI  - The three dominant female-sterile mutations of the Drosophila ovo gene are point
      mutations that create new translation-initiator AUG codons.
AB  - The Drosophila ovo gene, which encodes a putative transcription factor (Ovo) with
      TFIIIA-like zinc fingers, is required for female germline survival and proper
      oogenesis. Three dominant female-sterile ovoD mutations cause ovarian
      abnormalities that define an allelic series, with ovoD1 displaying the stronger
      phenotype and ovoD3 the weaker. We report here that all three ovoD mutations are
      point mutations that create new in-frame methionine codons in the 5' part of ovo.
      There are two types of overlapping ovo transcription units, ovo alpha and ovo
      beta. By using various ovo-lacZ reporter genes, we determined that the long Ovo
      isoforms starting at methionine M1, present in transcripts ovo alpha, are
      expressed at low levels only in mature oocytes. Short Ovo isoforms are translated
      from methionine M373, the first in-frame start codon present in transcript ovo
      beta, and correspond to the activity defined by recessive loss of function ovo
      mutations. The new AUGs created in ovoD mutations all are located upstream of the
      M373 initiation site. Our results support the hypothesis that they can substitute
      for M373 as translation starts and initiate the synthesis of Ovo proteins that
      have extra amino acids at their N termini. We propose that premature expression
      of long Ovo protein isoforms occurs in ovoD mutants and interferes with wild-type
      Ovo function in controlling female germline differentiation.

PMID- 9012533
TI  - Atonal, rough and the resolution of proneural clusters in the developing
      Drosophila retina.
AB  - In the developing Drosophila retina, the proneural gene for photoreceptor neurons
      is atonal, a basic helix-loop-helix transcription factor. Using atonal as a
      marker for proneural maturation, we examine the stepwise resolution of proneural
      clusters during the initiation of ommatidial differentiation in the developing
      eye disc. In addition, evidence is provided that atonal is negatively regulated
      by rough, a homeobox-containing transcription factor expressed exclusively in the
      retina. This interaction leads to the refinement of proneural clusters to specify
      R8, the first neuron to emerge in the retinal neuroepithelium. Ectopic expression
      of atonal or removal of rough results in the transformation of a discrete
      'equivalence group' of cells into R8s. In addition, ectopic expression of rough
      blocks atonal expression and proneural cluster formation within the morphogenetic
      furrow. Thus, rough provides retina-specific regulation to the more general
      atonal-mediated proneural differentiation pathway. The opposing roles of atonal
      and rough are not mediated through the Notch pathway, as their expression remains
      complementary when Notch activity is reduced. These observations suggest that
      homeobox-containing genes can provide tissue-specific regulation to bHLH factors.

PMID- 9012534
TI  - cdh-3, a gene encoding a member of the cadherin superfamily, functions in
      epithelial cell morphogenesis in Caenorhabditis elegans.
AB  - Several genes that encode members of the cadherin superfamily have been
      identified in Caenorhabditis elegans. Based on the roles of cadherins in
      vertebrates and Drosophila, it is expected that they function in the control of
      epithelial morphogenesis, an event which is poorly understood at the molecular
      level in C. elegans. Reporter genes under the control of upstream sequences from
      one of these genes, cdh-3, are expressed in developing epithelial cells, but also
      in a number of neuroectodermal cells that extend processes along some of these
      epithelial cells. We generated a loss-of-function mutation in cdh-3 by transposon
      mediated deletion mutagenesis. This mutation affects the morphogenesis of a
      single cell, hyp10, which forms the tip of the nematode tail. The lack of
      detectable defects associated with the other cells expressing cdh-3 reporter
      constructs hints at the existence of other genes that can compensate for cdh-3
      loss of function.

PMID- 9012535
TI  - Conditioned medium from a rat ureteric bud cell line in combination with bFGF
      induces complete differentiation of isolated metanephric mesenchyme.
AB  - Differentiation of metanephric mesenchyme is triggered by an inductive signal(s)
      from the epithelial ureteric bud. As a result of this induction, most of the
      metanephric mesenchyme converts into epithelium of a nephron. We have developed
      and characterized an explant culture system, in which metanephric mesenchyme can
      grow and completely differentiate in vitro in the absence of an inductive tissue.
      When separated 13 dpc rat metanephric mesenchymes were cultured in serum-free
      conditioned medium from a rat ureteric bud cell line (RUB1) in the presence of
      bFGF and TGFalpha, they were induced to differentiate into nephron epithelia and
      glomeruli-like structures. The nephric type of differentiation was confirmed by
      both morphological and molecular criteria and paralleled the developmental
      changes of nephron differentiation in vivo. Expression patterns of brush-border
      antigen as well as molecular markers of kidney differentiation Wt1, Lim1, Hgf and
      c-met, c-ret, Shh, Wnt4, Wnt7b, and Wnt11 were analyzed in explants by whole
      mount and tissue section in situ hybridization following 1-9 days in culture. The
      expression of secreted patterning molecules Bmp7 and Wnt7b, but not Shh or Wnt11,
      were demonstrated by RT-PCR and northern blot hybridization with RNA from the
      RUB1 cells. Our culture system lends itself to examining the relevance of these
      and other signaling molecules required for nephron differentiation.

PMID- 9012536
TI  - Function of the Drosophila POU domain transcription factor drifter as an upstream
      regulator of breathless receptor tyrosine kinase expression in developing
      trachea.
AB  - Organogenesis of the Drosophila tracheal system involves extensive directed cell
      migrations leading to a stereotypic series of interconnected tubules. Although
      numerous gene products have been shown to be essential for tracheal
      morphogenesis, direct functional relationships between participants have not been
      previously established. Both the breathless gene, encoding a Drosophila
      fibroblast growth factor receptor tyrosine kinase homologue, and the POU-domain
      transcription factor gene, drifter, are expressed in all tracheal cells and are
      essential for directed cell migrations. We demonstrate here that ubiquitously
      expressed Breathless protein under control of a heterologous heat-shock promoter
      is able to rescue the severely disrupted tracheal phenotype associated with
      drifter loss-of-function mutations. In the absence of Drifter function,
      breathless expression is initiated normally but transcript levels fall
      drastically to undetectable levels as tracheal differentiation proceeds. In
      addition, breathless regulatory DNA contains seven high affinity Drifter binding
      sites similar to previously identified Drifter recognition elements. These
      results suggest that the Drifter protein, which maintains its own expression
      through a tracheal-specific autoregulatory enhancer, is not necessary for
      initiation of breathless expression but functions as a direct transcriptional
      regulator necessary for maintenance of breathless transcripts at high levels
      during tracheal cell migration. This example of a mechanism for maintenance of a
      committed cell fate offers a model for understanding how essential gene
      activities can be maintained throughout organogenesis.

PMID- 9012537
TI  - The Xenopus T-box gene, Antipodean, encodes a vegetally localised maternal mRNA
      and can trigger mesoderm formation.
AB  - We have used differential display to identify genes inducible by activin and
      isolated a novel member of the T-box gene family that includes the Xenopus genes
      Xbrachyury and Eomesodermin. Here we show that this novel gene is unique within
      the T-box family because it is maternally expressed at a high level. Furthermore,
      it belongs to a rare class of maternal mRNAs in Xenopus that are localised to the
      vegetal hemisphere of the egg and we have therefore named it Antipodean. We show
      here that low amounts of Antipodean injected into ectoderm (animal cap cells)
      strongly induce pan mesodermal genes such as Xbrachyury and ventral mesodermal
      genes such as Xwnt-8. Overexpression of Antipodean generates mesoderm of ventral
      character, and induces muscle only weakly. This property is consistent with the
      observed late zygotic Antipodean mRNA expression in the posterior paraxial
      mesoderm and ventral blastopore, and its exclusion from the most dorsal
      mesodermal structure, the notochord. Antipodean is induced by several molecules
      of the TGF-beta class, but in contrast to Xbrachyury, not by bFGF. This result
      suggests that the expression of these T-box genes may be under the control of
      different regulatory pathways. Finally, we demonstrate that Antipodean and
      Eomesodermin induce each other and both are able to induce Xbrachyury. The early
      zygotic expression of Antipodean is not induced by Xbrachyury, though later it is
      to some extent. Considering its maternal content, Antipodean could initiate a
      cascade of T-box gene activations. The expression of these genes may, in turn,
      sustain each other's expression to define and maintain the mesoderm identity in
      Xenopus.

PMID- 9012538
TI  - Improvement of glucose tolerance with immunomodulators on type 2 diabetic
      animals.
AB  - Cytokine-inducers prevent insulin-dependent diabetes mellitus (IDDM) in animal
      models. We extend this therapy to non-insulin-dependent diabetes mellitus
      (NIDDM), because it was reported that diabetes of KK-Ay mice, a model for NIDDM,
      was recovered by allogenic bone-marrow transplantation that also prevented IDDM
      in animal models. An i.p. or i.v. injection of streptococcal preparation (OK-432)
      lowered fasting blood glucose (FBG) levels and markedly improved glucose
      tolerance test (GTT) in KK-Ay mice for more than 32 h regardless of the glucose
      loading routes (oral, i.v. or i.p.), while an i.v. injection of BCG improved FBG
      and GTT for more than 4 wks without body weight loss. The improvement of FBG and
      GTT with OK-432 was brought about in other NIDDM animals, GK rats and Wistar
      fatty rats. Among various cytokines possibly induced by OK-432 and BCG, IL-1
      alpha, TNF alpha and lymphotoxin significantly improved FBG and GTT in KK-Ay
      mice, whereas IL-2 and IFN gamma did not. There were no differences between the
      OK-432-treated KK-Ay mice and control in histology of the pancreas, degree of
      insulin-induced decrease in blood glucose levels, and muscle glycogen synthase
      activities. As to insulin secretion, there is a tendency that the OK-432
      treatment less that 1 week did not affect insulin levels during GTT, whereas the
      treatment more than 2 weeks increased the insulin levels. Thus, cytokine-inducers
      improved FBG and glucose tolerance of NIDDM animals probably via cytokines. The
      results imply a role of the cytokines in glucose tolerance of NIDDM, although
      precise immune and metabolic mechanisms remain to be elucidated.

PMID- 9012540
TI  - Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murine
      retrovirus and mechanisms involved in the prevention of disease progression.
AB  - Glycyrrhizin (GL), a plant extract, has been evaluated for its inhibitory effect
      on HIV replication in vitro and for its improvement of clinical symptoms in HIV
      infected patients. In this study, we used GL in a murine AIDS model (MAIDS) to
      evaluate these effects. C57BL/6 mice were inoculated with LP-BM5 murine leukemia
      virus to cause MAIDS. Treatment with GL supplemented with glycine and cysteine
      (Stronger Neo-Minophagen C, SNMC) was then begun on day 0 or 4 wks after virus
      inoculation. SNMC was administered three times a week for up to 19 wks.
      Immunological abnormalities were monitored with respect to the surface phenotype
      identified by two-color staining for CD3 and IL-2 receptor beta-chain. All mice
      infected with the virus alone developed MAIDS and died by 14 wks after infection.
      The immunopathogenesis was estimated to be an abnormal expansion of intermediate
      CD3 cells (i.e., extrathymic T cells) as well as other types of lymphocytes. SNMC
      did not change the total mortality rate. However, some mice that began the
      treatment on day 0 or 4 wks after infection survived 3 wks longer. Splenomegaly
      and lymphadenopathy in such mice were suppressed. These mice showed normal
      phenotypic features and normal responses to Con A. These results suggest that
      SNMC is effective in some MAIDS mice in preventing the progression of disease.
      When lymphocytes isolated from the liver, spleen and lymph nodes of diseased mice
      were cultured in vitro, they showed a spontaneous proliferation. Interestingly,
      such proliferation was inhibited by addition of liver lymphocytes, but not
      splenic lymphocytes, obtained from normal or SNMC-treated mice. Since liver
      lymphocytes contains intermediate CD3 cells with autoreactivity, they may
      possibly suppress the progression of disease.

PMID- 9012539
TI  - Antitumor effects of human recombinant interleukin-1 alpha and etoposide against
      human tumor cells: mechanism for synergism in vitro and activity in vivo.
AB  - Recombinant human interleukin 1 alpha (rh IL-1 alpha) and etoposide (VP-16)
      synergize for direct growth inhibition of several human tumor cell lines in
      vitro. Our previous studies demonstrated that VP-16 increased the number of
      membrane-associated IL-1 receptors (IL-1Rs) and also enhanced the internalization
      of receptor-bound rh IL-1 alpha. The purposes of this study were to test our
      hypotheses that these events were critical to the synergy between rhIL-1 alpha
      and VP-16, to determine whether rhIL- 1 alpha and VP-16 synergize to increase
      superoxide (SO) anion radical production in vitro since SO anion has been
      implicated in the toxic effects of IL-1, and to investigate the antitumor
      efficacy of the combination against tumors in vivo. A375/C6 melanoma cells and
      OVCAR-3 ovarian carcinoma cells were tested with IL-1 receptor antagonist (IL-1
      ra) before exposure to rhIL-1 alpha, VP-16 and rhIL-1 alpha plus VP-16. The
      synergistic or antagonistic effects were assessed by MTT assay. SO production was
      measured by reduction of cytochrome C. Athymic female mice bearing the A375/C6
      melanoma were treated by rhIL-1 alpha, VP-16, and rhIL- 1 alpha+VP-16. The
      antitumor effects were evaluated by quantitating tumor growth and survival time.
      Pretreatment with the IL-1ra abrogated the synergistic effects of rhIL-1 alpha
      and VP-16. The production of SO radical by A375/C6 cells was increased 2.5 fold
      by the combination of rhIL-1 alpha and VP-16, and the addition of exogenous SOD
      blocked the synergy between rhIL-1 alpha and VP-16. However, when A375/SOD15
      cells which over-expressed manganese superoxide dismutase (MnSOD) after MnSOD
      cDNA transfection were exposed to rhIL-1 alpha and VP-16, in vitro antagonism was
      observed. In vivo studies demonstrated that the combination of rhIL-1 alpha and
      VP-16 delayed tumor growth better than either agent alone, although long-term
      survival was not improved because of substantial toxicity. Our results suggest
      that the synergistic antitumor effects of IL-1 alpha and VP-16 may be due to IL
      1R modulation and increased internalization of IL-1-IL-1R complex by VP-16
      treatment, as well as to a subsequent increase in SO anion radical production
      from the tumor cells exposed to both drugs. Thus, the combination of IL-1 alpha
      and VP-16 might prove useful for the treatment of malignant disease in vivo, if
      the increased toxicity can be reduced or managed.

PMID- 9012541
TI  - Assessment of the effect of candidate anti-inflammatory treatments on the
      interaction between meningococci and inflammatory cells in vitro in a whole blood
      model.
AB  - A wide range of immunomodulating agents are now available which may be of benefit
      in reducing inflammatory cell activation in meningococcal sepsis. In order to
      facilitate selection of candidate anti-inflammatory agents for clinical trials,
      we have used an in vitro whole blood model to evaluate the effects on
      meningococcal induced neutrophil and monocyte activation, of dexamethasone,
      prostacyclin, pentoxifylline and a human IgM anti-lipid A monoclonal antibody (HA
      1A). Known concentrations of heat and penicillin killed meningococci were added
      to whole blood and the time course of cellular activation was determined. Using
      elastase alpha 1-antitrypsin (elastase-alpha 1-AT) and TNF alpha production as
      markers of neutrophil and monocyte activation respectively, plasma levels of
      elastase-alpha 1-AT and TNF alpha were found to increase in a dose-dependent
      manner. Elastase-alpha 1-AT was detected early, with most release occurring
      between 15-30 min whereas TNF alpha was detected later, between 120-180 min.
      Dexamethasone, prostacyclin and pentoxifylline caused a dose-dependent inhibition
      of TNF alpha release but had no effect on elastase release. HA-1A had no effect
      on either TNF alpha or elastase release. This model may be useful in determining
      the sequence of inflammatory cell activation and in selecting candidate anti
      inflammatory agents for evaluation in clinical trials.

PMID- 9012542
TI  - Morphological study of cytotoxicity produced by PSK-induced polymorphonuclear
      leukocytes (PMNs) and Nocardia rubra cell wall skeleton.
AB  - The morphologic changes in PMNs induced by an i.p. injection of PSK, a
      polysaccharide from the mycelia of Coriolus versicolor, and tumor cells
      undergoing cell death, were evaluated by immunohistochemical staining and
      electron microscopy. Male C3H/He mice, 8-10 -weeks old, received an i.p.
      injection of 125 mg/kg of PSK. Their PMNs were obtained 6 h after the PSK
      injection by peritoneal lavage. N-CWS (Nocardia rubra cell wall skeleton) was
      added at the start of the chromium release assay using the MM46 mammary carcinoma
      cell line, which is syngeneic to C3H/He mice, as target cells. During the
      cytotoxic assay, the cells were fixed at various time points. The MM46 cells
      expressed ICAM-1 while the PMNs expressed both ICAM-1 and LFA-1 as determined by
      immunohistochemical staining and immunoelectron microscopy using anti-ICAM-1 and
      anti-LFA-1 antibodies. PMNs with ruffle-like microvilli adhered to the MM46 tumor
      cells 30 min after the addition of N-CWS. Immunoelectron microscopic findings
      suggested that the adhesion molecules were LFA-1 on the PMNs and ICAM-1 on the
      MM46 tumor cells, but cell fusion between the PMNs and tumor cells was not
      observed. The MM46 tumor cells gradually lost their microvilli, which showed cell
      damage, and died 6-7 h after the addition of the N-CWS. This time course of tumor
      cell death is compatible with the results of the cytotoxic assay. Pretreatment of
      PMNs by anti-LFA-1 antibody suppressed 1% lysis of MM46 tumor cells from 90% to
      10% (p < 0.01). These data suggest that adhesion molecule on the surface of PMNs
      such as LFA-1 might play an important role on signal transduction of these PMNs
      cytotoxic function in this experimental system.

PMID- 9012543
TI  - Augmentation of antitumor effect by combined administration with interleukin-2
      and sizofiran, a single glucan, on murine EL-4 lymphoma.
AB  - The antitumor effect of the combined administration with recombinant human
      interleukin-2 (rIL-2) and sizofiran (SPG), a single glucan of Shizophyllum
      commune Fries, was studied in vivo in C57BL/6 mice intraperitoneally inoculated
      with EL-4 lymphoma. The effect was evaluated by a) comparing the survival time of
      the mice, b) analysis of the intraperitoneal cell population in Giemsa-stained
      specimens, c) surface marker analysis of peritoneal exudative cells with flow
      cytometry, d) cytotoxic assay of cells against EL-4 and Yac-1 lymphoma, and e)
      elimination of some cell populations by monoclonal antibodies, to identify the
      antitumor-effector cells showing cytotoxic activity. The survival of mice given
      both rIL-2 and SPG was significantly longer than the control mice or those given
      SPG alone or rIL-2 alone. It was demonstrated that the administration of SPG
      and/or rIL-2 to the EL-4 lymphoma-bearing mice activated immune-response cells in
      the peritoneal cavity such as T lymphocytes, NK cells, or macrophages, which
      might be effective in reducing lymphoma cells. The combination of rIL-2 and SPG
      administration appears to activate the antitumor-immune response at the tumor
      site more effectively than when either agent was administered alone.

PMID- 9012544
TI  - Effect of Z-100, an immunomodulator extracted from human type tubercle bacilli,
      on the pulmonary metastases of Lewis lung carcinoma in attempt to regulate
      suppressor T cells and suppressor factor, IL-4.
AB  - In the present study, anti-metastatic effect of Z-100 on the spontaneous
      pulmonary metastases of Lewis lung carcinoma (3LL) was examined in an attempt to
      regulate suppressor T cells. When Z-100 (10 mg/kg) was daily injected i.p. after
      3LL inoculation, survival rate of these mice was increased significantly (p <
      0.05). In addition, the number of pulmonary metastatic colonies of 3LL in Z-100
      treated mice were significantly decreased by 38% at 21 days, as compared with
      that of control mice (p < 0.05). Along with the decrease of pulmonary metastases,
      suppressor cell activity was also gradually reduced in these mice, as compared
      with that of control mice. When splenic suppressor cells (5 x 10(7) cells) from
      3LL-bearing mice were adoptively transferred into normal mice (recipients) just
      before inoculation of 3LL, the development of pulmonary metastases in recipients
      was significantly accelerated. However, splenocytes from 3LL-bearing mice treated
      with Z-100 did not affect the development of pulmonary metastasis. The potential
      to accelerate the metastasis of splenic mononuclear cells from 3LL-bearing mice
      was decreased significantly by the treatment with anti-Thy 1.2 monoclonal
      antibody (mAb), anti-Lyt 2.2 mAb or anti-CD 11b mAb followed by complement. IL-4
      activity in the sera of 3LL-bearing mice was detected 15 days after tumor
      inoculation (13 pg/ml) and gradually increased (18 pg/ml) 20 days after tumor
      inoculation. However, when Z-100 (10 mg/kg) was daily injected i.p., IL-4
      activity in sera was decreased significantly, and the IL-4 activity was not
      detected in these mice on day 20. These results suggest that Z-100 could inhibit
      the pulmonary metastases in 3LL-bearing mice through the inhibition of suppressor
      T cell activity and a possible candidate of its effector molecule, IL-4.

PMID- 9012545
TI  - Effect of sizofiran on regional lymph nodes in patients with head and neck
      cancer.
AB  - The immunomodulating effects of preoperative sizofiran (SPG) administration on
      regional lymph nodes were studied in patients with stage III or IV head and neck
      cancer, by comparing the immunofunction of peripheral blood. The regional lymph
      nodes were dissected surgically, and freshly obtained mononuclear cells were
      studied to investigate the interleukin 2 (IL-2) production, the LAK and NK
      activities, and the quantitative analysis of the surface phenotype of the
      mononuclear cells. The results indicated that SPG enhanced immunological
      activities in the regional lymph nodes, as shown by increased IL-2 production and
      cytotoxic activities of the effector cells (NK, LAK), and increased helper T
      lymphocytes (CD4+) in the tumor-uninvolved lymph nodes. The immunofunction
      following SPG administration was attenuated, but was still augmented in the
      regional lymph nodes with metastases. Therefore, SPG was found to be a biologic
      response modifier to enhance the immunofunctions of the regional lymph node in
      patients with head and neck cancer.

PMID- 9012547
TI  - Family needs after traumatic brain injury: a factor analytic study of the Family
      Needs Questionnaire.
AB  - The present investigation examined the empirical and theoretical validity of an
      instrument developed to assess family members' perceptions of needs following the
      brain injury of a relative. The Family Needs Questionnaire (FNQ) consists of 40
      items reflecting commonly reported family needs. The development of the items was
      based on the literature describing family reactions to brain injury and other
      medical disabilities. A principal-components factor analysis was executed based
      on the FNQ responses of 178 family members. A six-factor solution was selection
      as the best fit for the data, yielding the following independent subscales: (1)
      Need for Health Information; (2) Need for Emotional Support; (3) Need for
      Instrumental Support; (4) Need for Professional Support; (5) Need for a Support
      Network; and (6) Need for Involvement with Care. Further analysis indicated at
      least adequate internal reliability for each scale. Overall, the measure appears
      to offer unique information relevant to family members' needs after brain injury.

PMID- 9012546
TI  - Inhibitory effect of metastasis by combined administration with interleukin-2 and
      sizofiran, a single glucan--immunohistochemical study.
AB  - Innovations in methods of combined administration with other BRM or
      chemotherapeutic drugs have been discussed. We have reported that combined
      administration with recombinant interleukin-2 (rIL-2) and sizofiran (SPG) is
      effective in prolonging survival time of C57BL/6 mice intraperitoneally
      inoculated with EL-4 lymphoma. The immunomechanisms of the combined
      administration were clarified investigating the intraperitoneal cell population
      in the primary tumor site, especially the tumor infiltrating lymphocyte (TIL)
      quantitatively. In the present study, to clarify the antitumor effects of
      combined administration with rIL-2 and SPG on the metastatic sites, the
      immunomechanisms of the suppressive effects of combined administration on the
      metastasis were studied in EL-4 lymphoma cells intraperitoneally transplanted to
      mice. Inasmuch as EL-4 lymphoma shows rapid hepatosplenic metastasis, we studied
      the metastatic foci in the liver and the spleen semiquantitatively in
      investigating the histopathological and immunohistochemical findings of the
      metastatic foci, especially the TIL. The metastatic foci were stained by
      hematoxylin-eosin (HE) and monoclonal antibodies (L3T4, Lyt2, asialo GM1, Mac-1,
      and Ia). The combined administration resulted in: 1) fewer infiltrating tumor
      cells, 2) more lymphocytic infiltration, and 3) more antitumor effector cells
      (cytotoxic T cells: Lyt2 and natural killer cells: asialo GM1), macrophages (Mac
      1), helper T cells (L3T4), and cells with MHC-class-II antigen (Ia) than did
      administration of rIL-2 alone or SPG alone, or no administration of these two at
      all. Combined administration with rIL-2 and SPG appears to activate antitumor
      immune response at the metastatic site more effectively than when either agent is
      administered alone.

PMID- 9012548
TI  - Impact of childhood brain injury on work and family finances.
AB  - Parents of children who suffer brain injuries are often surprised by the extent
      to which work and family finances are disrupted. In this paper, work and
      financial problems are described, predictors are identified, and ways to minimize
      problems are discussed. Eighty-two children treated at two Massachusetts trauma
      centres were given an extensive battery of medical, functional, and psychosocial
      tests during hospitalization. At 1 and 6 months post-discharge they were retested
      and their parents were surveyed about work and financial difficulties. Trouble
      maintaining regular work schedules and injury-related financial problems were
      common. At highest risk for work and financial problems were families of children
      with severe injuries who had four to nine impairments, along with children
      hospitalized > 2 weeks who were not discharged to home. Surprisingly, families
      with HMO coverage reported significantly fewer financial problems, and this
      relationship was not due to differences in socioeconomic status or injury
      severity. Health-care providers need to pay more attention to the potential
      impact of injury on work and family finances. Providers can help at-risk families
      muster child-care services, deal effectively with employers and insurance
      companies, and plan for the future.

PMID- 9012549
TI  - Visual electrodiagnostic findings in mild traumatic brain injury.
AB  - Patients with traumatic brain injury (TBI) frequently exhibit varied forms of
      visual system dysfunction including: binocular, oculomotor, accommodative,
      refractive error shift, visual field loss, and visual perceptual deficits. A 5
      year collaborative study between optometry and ophthalmology was initiated to
      follow documented mild TBI patients utilizing diagnostic methods to assess the
      quantity and quality of visual system deficits and recovery. A group of patients
      with mild TBI receiving optometric rehabilitation were compared with a group of
      age-matched, gender-matched, and headsize-matched TBI patients not receiving such
      treatment. Eighteen patients diagnosed with mild TBI underwent a treatment
      regimen of optometric rehabilitation (group I); 32 patients diagnosed with mild
      TBI did not receive optometric rehabilitation (group II). Pattern visually evoked
      cortical potential (VECP) testing and electroretinography (ERG) evaluation were
      utilized initially, repeated 6-12 months later and then 12-18 months after
      baseline. All TBI patients' VECP and ERG results were compared to age-matched,
      headsize-matched controls. Once the ERG had been used to exclude retinal
      involvement, identification of visual pathway dysfunction was possible with the
      VECP. Full-field ERG results in all groups were not remarkable and not sensitive
      for patients with mild TBI. Initial testing results revealed that 72% of those
      TBI patients in group I demonstrated VECP waveform abnormalities and 81% of those
      patients in group II showed waveform dysfunction. In the testing performed 12-18
      months later, 38% of group I TBI patients, after receiving a treatment regimen of
      optometric rehabilitation, showed VECP waveform abnormalities; 78% of group II
      TBI patients demonstrated waveform abnormalities. VECP evaluation in patients
      with mild TBI can provide a useful and reliable tool for objective assessment of
      visual system deficit and recovery. Significant differences in visual system
      recovery were shown when comparing group I and group II.

PMID- 9012550
TI  - Effectiveness of valproic acid on destructive and aggressive behaviours in
      patients with acquired brain injury.
AB  - Valproic acid, a primary anticonvulsant drug, has recently been studied for
      purported effectiveness in disparate disorders of mood and behaviour. The
      psychopharmacological treatment of patients with acquired brain injury frequently
      includes numerous trials of psychotherapeutic drugs such as antipsychotics,
      benzodiazepines, antidepressants, and lithium, in an effort towards affective and
      behavioural improvement. In this report we describe and graphically depict the
      striking efficacy of valproic acid in reducing and improving destructive and
      aggressive behaviours in five patients with acquired brain injury. In all cases
      valproic acid was effective after other pharmacological interventions were not.
      Also, the addition of valproic acid was followed by neurobehavioural improvement
      rather quickly, often within 1-2 weeks. Advantages of valproic acid, in addition
      to its possible unique efficacy, include a lower propensity towards sedation and
      cognitive impairment, and thus a more robust potential for rehabilitation
      participation. Behaviours associated with affective disorders ranging along the
      affective spectrum from depression to dysphoric mania may be particularly
      amenable to valproic acid. The drug may also be beneficial in some cases in which
      another psychotropic anticonvulsant, carbamazepine, was not.

PMID- 9012551
TI  - Correlation of functional independence measure (FIM) and SPECT Iofetamine (I-123)
      as a predictor of functional return in stroke.
AB  - Function following stroke is often measured using the Functional Independence
      Measure (FIM). Independence occurs when the patient achieves certain levels of
      functions. SPECT imaging assesses the regional cerebral blood flow (rCBF). Is it
      possible to correlate the FIM scores with SPECT imaging and predict functional
      return? We evaluated total of 69 stroke patients with SPECT imaging using
      Iofetamine (I-123). Patients were scanned within 14-21 days post-stroke. CT scans
      were evaluated and correlated with the SPECT images. This information was
      compared with the admission and discharge FIM scores. The rCBF reperfusion
      changes and region of stroke were evaluated and correlated with discharge
      functional status. The right parietal areas demonstrated a strong correlation
      with SPECT and FIM changes as predictors of return of functional living status (p
      value = 0.0438). The right parietal area demonstrated an improvement in
      ambulation (p-value = 0.0578); the right brain correlated with overall
      improvement in FIM scores and change in SPECT imaging (p-value = 0.0833); the
      left brain did not exhibit significant values. Our conclusion was that there were
      trends seen with the predictive value of stroke recovery using SPECT imaging. The
      current sample number was not large enough to provide an adequate study,
      especially for the left brain; a larger study is needed. This information could
      be useful to help determine patient placement for rehabilitation.

PMID- 9012552
TI  - Effect of stimulus number, target-to-distractor ratio, and motor speed on visual
      spatial search quality following traumatic brain injury.
AB  - The object of this study was to investigate stimulus effects and motor
      limitations on visuospatial performance after traumatic brain injury (TBI).
      Previous findings have not fully explained the basis of attentional impairments
      after TBI. There has been little study of the spatial aspects of attention and
      information processing in this group. We studied 20 patients after severe TBI and
      21 healthy controls. Four random-array letter cancellation tasks, varying in
      number of stimuli (50 and 100) and target-to-distractor ratio (1:4 and 1:9) were
      employed. Performance was calculated from the number and proportion of cancelled
      targets, as well as time to completion. TBI subjects were slower on finger
      tapping and achieved lower cancellation performance scores. Both TBI subjects and
      controls performed better on tasks with target-to-distractor (T/D) ratios of 1:4
      than on those with 1:9. There was no effect of stimulus number. We conclude that
      there are both quantitative (speed) and qualitative contributors to impaired
      visuospatial ability following TBI. Motor impairments may slow the overall
      cancellation performance, but the differential effect of T/D ratio in the two
      populations suggests that TBI impairs quality of research. Accounting for both
      speed and accuracy suggests increased utility for the cancellation paradigm in
      clinical and research assessment of visuospatial attention.

PMID- 9012553
TI  - Reliability for a walk/run test to estimate aerobic capacity in a brain-injured
      population.
AB  - The purpose of this study was to establish the test-retest reliability of a
      modified 20 m shuttle walk/run test of aerobic capacity for adults with traumatic
      brain injuries (TBI). A convenience sample of 18 TBI patients (16 males, two
      females) between 19 and 58 years of age, was tested using an externally paced,
      progressive, maximal shuttle walk/run, on two separate occasions, within a 1-week
      period. The test involving walking or running a 20 m shuttle course while
      maintaining the pace determined by signals from a prerecorded audiotape. The
      initial slow walking pace (2.4 km/h) was increased gradually, each minute, until
      the patient could not continue. Statistical analyses revealed excellent
      reliability for the number of levels completed (ICC = 0.976), total walk/run test
      time (S) (ICC = 0.983) and maximal heart rate attained during the final level
      (bpm) (ICC = 0.964). Although small but significant increases were noted for the
      number of levels completed during the second test, the modified 20 m shuttle
      walk/run seems to be a reliable field test which may be useful for assessing the
      aerobic capacity of brain-injured adults.

PMID- 9012554
TI  - Pharmacokinetic-pharmacodynamic profile of angiotensin II receptor antagonists.
AB  - The pharmacokinetic and pharmacodynamic properties of nonpeptide angiotensin
      antagonists in humans are reviewed in this paper. Representatives of this new
      therapeutic class share common features: lipophilia, intermediate
      bioavailability, high affinity for plasma proteins and liver metabolism; some
      have active metabolites. Angiotensin II antagonists block the blood pressure
      response to exogenous angiotensin II in healthy volunteers, decrease baseline
      blood pressure in both normal and hypertensive patients, produce a marked rise in
      plasma renin activity and endogenous angiotensin II and increase renal blood flow
      without altering glomerular filtration rate. These effects are dose-dependent,
      but their time course varies between the drugs owing to pharmacokinetic and
      pharmacodynamic differences. Additionally, the extent of blood pressure reduction
      is dependent on physiological factors such as sodium and water balance. The
      characterisation of their pharmacokinetic-pharmacodynamic relationships deserves
      further refinement for designing optimal therapeutic regimens and proposing
      dosage adaptations in specific conditions.

PMID- 9012556
TI  - Dose-response of inhaled drugs in asthma. An update.
AB  - The demographic characteristics of patients used in clinical trials (such as the
      severity of airway obstruction) can significantly influence the results of dose
      response studies, emphasising the need to evaluate effects on the steep part of
      the dose-response curve. Differences in inhaler devices can also influence study
      outcomes, as for inhaled drugs both airway efficacy and adverse effect profiles
      are primarily determined by lung deposition and hence bioavailability. Dose
      response studies with short- and long-acting beta 2-agonists show an excellent
      therapeutic ratio at conventional doses used in everyday clinical practice (i.e.
      2 to 4 puffs). Dose-related systemic effects of beta 2-agonist occur at higher
      doses, for salbutamol (albuterol) > 500 micrograms. Fenoterol is a beta 2
      agonists with higher intrinsic activity than salbutamol and produces greater
      systemic effects at higher than conventional doses on a microgram equivalent
      basis, although even at 4000 micrograms such differences are unlikely to be
      clinically relevant. No differences between fenoterol and salbutamol have been
      shown in terms of bronchodilator potency on a microgram equivalent basis. The
      long-acting beta 2-agonist salmeterol, as a partial agonist, has the potential to
      attenuate the acute bronchodilator response to a higher activity beta 2-agonist
      such as salbutamol or fenoterol, although there is no evidence to date on whether
      this is relevant in the setting of acute asthma. When comparing inhaled
      corticosteroids, attention should be focused on their respective risk-benefit
      ratios for antiasthmatic versus systemic activity. In terms of detecting systemic
      activity, it is important to use sensitive measures, such as urinary cortisol
      excretion, rather than insensitive parameters, such as a single morning plasma
      cortisol measurement between 0800h and 1000h. For fluticasone, a greater in vitro
      potency results in only marginal differences in antiasthmatic efficacy,
      particularly on the flatter part of the dose-response curve above 1000
      micrograms/day in adults and 400 micrograms/day in children. However, the same
      enhanced potency translates directly into commensurate differences in systemic
      adverse effects on the steep part of the systemic dose-response curve above 1000
      micrograms/day in adults and 400 micrograms/day in children, respectively.
      Furthermore, with repeated twice-daily administration, a longer elimination half
      life and prolonged systemic tissue retention due to enhanced lipophilicity will
      result in greater systemic activity observed at steady-state in long term
      administration studies. This dissociation of airway and systemic dose-response
      curves results in a J-shaped curve for benefit: risk ratio, with a watershed area
      above 1000 microgram/day in adults. This fall in the benefit: risk ratio is
      likely to be greater for fluticasone than for budesonide or beclomethasone.
      Further studies are needed to clearly define the dose-response relationships of
      higher potency steroids such as fluticasone, particularly on the steep part of
      the curve (for clinical efficacy), using the appropriate back-titration design
      along with sensitive measures of antiasthmatic and systemic activity.

PMID- 9012555
TI  - Principles of drug administration in renal insufficiency.
AB  - Normal renal function is important for the excretion and metabolism of many
      drugs. Renal diseases which affect glomerular blood flow and filtration, tubular
      secretion, reabsorption and renal parenchymal mass alter drug clearances and lead
      to the need for alterations in dosage regimens to optimise therapeutic outcome
      and minimise the risk of toxicity. Renal disease is increasing and the cost of
      care has risen progressively over the past decade. Part of these costs is related
      to inappropriate drug therapy and excessive drug use. Although there are a
      variety of methods for evaluating the various aspects of renal function, the most
      practical and commonly used clinical measure of renal function is estimated
      creatinine clearance (CLCR) as a marker for glomerular filtration. This is useful
      since alterations in drug clearance are proportional to alterations in CLCR, and
      this relationship is used as the basis for changing doses and dosage intervals
      for drugs which are largely renally excreted. Two populations, neonates and the
      elderly, are at risk of inappropriate drug dosage due to physiological changes in
      renal function. Estimated CLCR may not be the best method of evaluating renal
      function in these patients, and dosage regimens should be carefully considered.
      Renal insufficiency and concurrent drug therapy used in these populations can
      either increase or decrease drug absorption, depending on the particular agent.
      Drug distribution may be altered in renal insufficiency due to pH-dependent
      protein binding and reduced protein (primarily albumin) levels. Interestingly,
      renal disease may affect hepatic as well as renal drug metabolism; the exact
      mechanisms for these changes are not well understood. The most important
      quantitative pharmacokinetic change is excretion. Glomerular filtration and
      tubular process may both be affected but not to the same extent, and the type of
      renal disease may differentially affect filtration and excretion. Drug removal by
      dialysis is dependent on a number of factors, including the characteristics of a
      particular drug and the type of dialysis and equipment used. Therapeutic outcomes
      may be evaluated using end-points such as plasma concentrations, patient outcomes
      such as reduction in fever or negative cultures, and system-wide changes such as
      drug-use or laboratory-use patterns.

PMID- 9012558
TI  - Introduction to the basics of arthroscopy of the knee.
AB  - Knee arthroscopy has benefited greatly over the past 2 decades from new
      developments in technology and instrumentation. These advances have transformed
      arthroscopy from a purely diagnostic procedure to one through which extensive and
      intricate surgery can be performed. In addition, the new technology and
      instruments now place the orthopedic surgeon at the threshold of successful
      arthroscopic surgery in the office. Attention to the basics ancillary to the
      actual surgery, however, are still of prime importance in ensuring complication
      free arthroscopic procedures.

PMID- 9012557
TI  - Bioequivalence of controlled-release calcium antagonists.
AB  - In this review, several deficiencies of published bioequivalence studies for
      controlled-release calcium antagonists have become apparent. As a consequence,
      some of the published conclusions based on such studies must be viewed with care.
      A proper statistical analysis of bioequivalence is not frequently reported. A
      proper statistical analysis of the pharmacokinetic variables involves the
      calculation of 90% confidence intervals (CI) for the test: reference ratio of the
      means of the pharmacokinetic variables of the test and reference product. The CI
      must fall completely within the predetermined bioequivalence range (usually 0.8
      to 1.25) for the products to be declared bioequivalent. Serious methodological
      errors, such as a conclusion of bioequivalence based on a lack of statistically
      significant difference between products, and conversely, a conclusion of
      bioequivalence because of a statistically significant difference, or because of a
      mere failure to show bioequivalence, are still made. With calcium antagonists in
      particular, an assessment of the rate of absorption and of the maximum
      concentration is important, as those characteristics may have implications for
      the safety profile with this class of drugs. As a minimum, in single doses
      studies the maximum concentration (Cmax), and the time to the maximum
      concentration (tmax), and in multiple-dose studies the Cmax, and the peak-trough
      fluctuation (%PTF) must be considered. Some bioequivalence studies of calcium
      antagonists are deficient in this respect. To show bioequivalence for controlled
      release formulations, multiple-dose studies are required but some published
      bioequivalence studies contain only single-dose assessments. Similarly,
      bioequivalence studies under fed conditions are rarely published, although food
      may have a significant effect on the absorption rate of these drugs. Some calcium
      antagonists, such as verpamil, show stereo-selective pharmacokinetics, so that
      enantiomers may have to be investigated. Unfortunately, few of the published
      studies of controlled-release calcium antagonists satisfy all requirements. One
      would expect that data submitted to regulatory authorities for approval of
      generic formulations are more complete; published data are in many cases not
      satisfactory.

PMID- 9012559
TI  - Arthroscopy of the patellofemoral joint.
AB  - There are multiple causes of patellofemoral pain that can be difficult to
      differentiate. A careful history and physical examination along with appropriate
      radiographic evaluation lead to the correct diagnosis in most cases. Most
      patients respond to a comprehensive nonoperative program that emphasizes
      stretching and strengthening of the quadriceps mechanism. Arthroscopy should be
      used judiciously when approaching patellofemoral problems. Regarding alignment,
      arthroscopy offers little benefit but may provide visualization for lateral
      release to relieve tilt. Arthroscopy of the patellofemoral joint does provide
      valuable information about articular cartilage breakdown location, extent, and
      pattern, which may help with future treatment decisions. Arthroscopy is helpful
      in the diagnosis and treatment of plicae and in ruling out other intraarticular
      causes of knee pain.

PMID- 9012560
TI  - Open or arthroscopic lateral release. Indications, techniques, and
      rehabilitation.
AB  - Careful patient selection, accurate surgical technique, and careful postoperative
      rehabilitation are all equally important to success in lateral release surgery.
      Whether the surgery is performed by open or arthroscopic technique, one must
      release all layers of the retinaculum, spare the vastus lateralis, extend the
      release far enough distally, check intraoperative patellar mobility, and obtain
      absolute hemostasis. Postoperative rehabilitation must stress pain control, early
      quadriceps contraction, patellar mobility, and knee motion. With attention to
      these details, successful lateral release surgery is likely in most patients with
      pathologic lateral patellar tilt and minimal patellofemoral arthrosis.

PMID- 9012561
TI  - Arthroscopic treatment of the degenerative knee in older athletes.
AB  - The role of arthroscopy in the management of degenerative knee arthritis in the
      older athlete remains controversial. This patient population desires symptomatic
      improvement to maintain active lifestyles. For advanced tricompartmental
      osteoarthritis, total knee arthroplasty provides the most predictable results.
      For active patients with unicompartmental disease, osteotomy can provide
      symptomatic improvement and delay the time to total knee arthroplasty.
      Substantial morbidity is associated with both of these procedures. Arthroscopic
      management of degenerative arthritis is an attractive alternative to osteotomy or
      total knee arthroplasty if predictable improvement and durable results can be
      achieved. Arthroscopic lavage success rates are quite variable and decline
      rapidly over time. It is mainly a palliative procedure with limited long-term
      success. Success rates for arthroscopic partial meniscectomy and arthroscopic
      debridement vary between 50% and 75% depending on many factors, including the age
      of the patient, degree of arthritis, activity level of the patient, limb
      alignment, and extent of follow-up. Lavage is probably an important aspect of
      this procedure. Abrasion arthroplasty and the Pridie procedure do not appear to
      offer any additional benefit to arthroscopic debridement alone. In fact, studies
      comparing arthroscopic abrasion with arthroscopic debridement have shown that
      debridement alone gives better long-term results than debridement combined with
      abrasion. Several studies have shown that some patients become significantly
      worse following abrasion arthroplasty. Clearly, arthroscopic debridement is the
      preferred procedure to abrasion arthroplasty. The arthroscope is useful in the
      treatment of degenerative arthritis of the knee. It has low morbidity and does
      not preclude future reconstructive procedures. Although long-term success is
      difficult to predict, certain patient variables are associated with a better
      outcome: normal limb alignment, history of mechanical symptoms, minimal
      radiographic signs of degeneration, and short duration of symptoms. Long-term
      randomized prospective studies are needed to define the role of arthroscopy
      further in the older athlete with degenerative knee arthritis.

PMID- 9012562
TI  - Arthroscopic medial meniscal repair in the athlete.
AB  - Meniscal tears are common sports injuries. This article details the clinical
      evaluation of the athlete presenting with knee pain. Conservative (nonoperative)
      treatment and arthroscopic procedures are discussed.

PMID- 9012563
TI  - Synovial plicae of the knee. Controversies and review.
AB  - Plicae are some of the normal synovial structures of the knee joint cavity. They
      are remnants of the mesenchymal tissue that occupies the space between the distal
      femoral and proximal tibial epiphyses in the 8-week-old embryo. The incomplete
      resorption leaves synovial pleats in most of the knee. The superior and the
      inferior plicae are the most common (50% to 65%) but have extremely little
      clinical relevance. Each may be of many various morphological types. The lateral
      plica is rare (1% to 3%). The medial plica is present at autopsies in one of
      every three or four knees. It also is of various types, wide and thick in one of
      every fifteen knees. Arthrography, ultrasonography, CT scan with arthrography,
      and MR imaging can demonstrate their presence and measure their size with good
      accuracy. Arthroscopy allows a very precise assessment of the plica, including
      dynamic examination. It looks for medial impingement against the patellofemoral
      articular surfaces and secondary (localized chondromalacia) as well as
      incidentally associated other knee pathologic conditions. Rarely, the medial
      plica becomes symptomatic, circumstances such as a history of blunt trauma, or
      more often, overuse of the knee can cause symptoms. Sometimes no special
      condition is necessary. The plica causes symptoms such as pain, crepitus,
      snapping or popping, or effusion related to patellofemoral joint motion. The
      clinical picture mimics a torn medial meniscus or a maltracking patella. Clinical
      examination is extremely helpful if the snapping plica is palpated at the medial
      edge of the patella, reproducing the patient's symptoms. If chronic, these
      symptoms may be treated with nonsteroidal anti-inflammatory drugs, physiotherapy,
      electrophoresis, or local injection. Surgical treatment is indicated if
      conservative therapy fails. Arthroscopic complete resection of the plica cures
      the symptoms in a few days, therefore confirming the correct diagnosis and the
      effectiveness of the treatment. Histologic examination often confirms the chronic
      conflict between the plica and the femoral condyle. No morphologic character
      allows the assessment of the pathologic aspect of the plica. A medial plica is or
      is not symptomatic. The incidence of this syndrome is probably one out of ten
      medial plicae and 3% of arthroscopies at most. Associated lesions are very
      common. They often make the evaluation of the plica's responsibility in symptoms
      difficult to analyze, leading to unsatisfactory results.

PMID- 9012564
TI  - Arthroscopic anterior cruciate ligament reconstruction.
AB  - Significant advances in arthroscopic techniques have led to wide-spread
      performance of arthroscopically assisted ACL reconstruction. Properly performed
      reconstruction has proved to be successful clinically. The surgeon who undertakes
      ACL reconstruction must be familiar with techniques for both autograft hamstring
      augmentation and bone-patellar tendon-bone ACL reconstruction for the ACL
      deficient knee. The arthroscopic techniques discussed in this article will allow
      successful treatment of most acute and chronic ACL injuries. Arthroscopic ACL
      reconstruction is a highly demanding procedure, with the possible risk of
      significant knee disability if the ACL graft is placed improperly. Proper patient
      selection, surgical technique, and postoperative rehabilitation remain the
      foundations for successful ACL reconstruction.

PMID- 9012565
TI  - Arthroscopic posterior cruciate ligament reconstruction.
AB  - Operative treatment of posterior cruciate ligament (PCL) injury is becoming more
      common as understanding of the natural history of the untreated PCL-deficient
      knee increases and the surgical techniques improve. The current recommendations
      for surgical reconstruction include patients with multiple ligament injuries and
      patients with isolated grade III PCL injuries. An understanding of the anatomy
      and biomechanics of the PCL is essential for successful reconstruction. This
      article presents a reproducible surgical technique for arthroscopically assisted
      PCL reconstruction.

PMID- 9012566
TI  - Osteochondritis dissecans of the distal femur and patella.
AB  - Osteochondritis dissecans (OCD) is a pathologic process characterized by a
      partial or total separation of a fragment of bone with overlying articular
      cartilage. OCD may affect any joint, but the knee joint is affected most
      commonly. This article reviews several potential causes of OCD and classification
      systems for OCD. Diagnosis and treatment strategies are discussed.

PMID- 9012567
TI  - Textural parameters based on the Spatial Gray Level Dependence Method applied to
      melanocytic nevi.
AB  - The purpose of this study is to evaluate the Spatial Gray Level Dependence Method
      (SGLDM) of texture analysis with respect to its ability to discriminate between
      melanocytic nevi and normal skin. Thirteen textural features based on the SGLDM
      were evaluated with respect to their relative sensitivities to both texture and
      tone. Ten features were found to be more sensitive to texture than tone and were
      selected for further study. Twenty-four digitized images of benign melanocytic
      nevi were obtained from six volunteers. Ten textural features were analyzed for
      each nevus and for surrounding sections of normal skin. Of these 10 features, 8
      features can distinguish between textural properties of melanocytic nevi and
      surrounding skin.

PMID- 9012568
TI  - Statistical methods in the Fourier domain to enhance and classify images.
AB  - A mathematical model, for which rigorous methods of statistical inference are
      available, is described and techniques for image enhancement and linear
      discriminant analysis of groups are developed. Since the gray values of
      neighboring pixels in tomographically produced medical images are spatially
      correlated, the calculations are carried out in the Fourier domain to insure
      statistical independence of the variables. Furthermore, to increase the power of
      statistical tests the known spatial covariance was used to specify constraints in
      the spectral domain. These methods were compared to statistical procedures
      carried out in the spatial domain. Positron emission tomography (PET) images of
      alcoholics with organic brain disorders were compared by these techniques to age
      matched normal volunteers. Although these techniques are employed to analyze
      group characteristics of functional images, they provide a comprehensive set of
      mathematical and statistical procedures in the spectral domain that can also be
      applied to images of other modalities, such as computed tomography (CT) or
      magnetic resonance imaging (MRI).

PMID- 9012569
TI  - Measures of uncertainty of pharmacokinetic and pharmacodynamic parameter
      estimates: a new computerized algorithm.
AB  - Numerous algorithms exist to fit data to nonlinear models of the type used in
      chemistry, pharmacology, physiology, etc. Most include modules that provide some
      measure of the reliability of the estimated model parameters. The variance
      covariance matrix (VCM) is the common tabulation of information that is used to
      quantify the parameter uncertainty as well as correlations between parameters.
      The VCM has its mathematical foundation in the linear regression world, where the
      dependent variable is a linear function of the parameters. However, when the
      model is not linear in its parameters, then the VCM is no longer an absolute
      quantitative measure of reliability of the parameter estimates and should be
      interpreted with caution. If the goal is to obtain a realistic and quantitative
      rather than a qualitative measurement of the parameter reliability, then it is
      necessary to have an alternative approach to describe the parameter likelihood
      region. We present a computerized algorithm that fills that need, and we compare
      its performance with the traditional VCM approach for different data sets. We
      also discuss criteria that may be used to determine when the VCM approach should
      and should not be used.

PMID- 9012571
TI  - EMBASE remains EMBASE--on every host? A comparative analysis of EMBASE on the
      hosts DATA-STAR, DIALOG, DIMDI, and STN.
AB  - Differing results of the same search request processed on different hosts led the
      authors to investigate this issue more thoroughly. Two authors, two journal
      titles, two drug names, and two topics of a general medical nature were retrieved
      under identical circumstances and conditions on the hosts DATA-STAR, DIALOG,
      DIMDI, and STN. Comparing the figures revealed that none of the nine search
      request produced an identical result on all hosts. Some of the search results
      differed only slightly, while the searches in the basic index produced
      considerable discrepancies.

PMID- 9012570
TI  - Nearest-neighbor analysis of spatial point patterns: application to biomedical
      image interpretation.
AB  - Analysis of the spatial distributions of objects is fundamental to biomedical
      image interpretation. Nearest-neighbor (NN) methods are generally used to assess
      whether objects are arranged at random or in a deterministic manner. Simple
      standard NN techniques, however, may fail to identify complex spatial
      organizations. To overcome this problem the present study proposes a NN iterative
      algorithm that enables deterministic spatial patterns to be detected by
      identifying the distances between objects for which there is the greatest
      deviation from randomness and hence the amplitude of the areas of maximum
      reciprocal influence between objects. The performance of the algorithm is
      evaluated by applying it to both manufactured and experimental data. The
      manufactured date example showed that the proposed procedure produced neither
      false positives or negatives. The method proved to be extremely sensitive,
      detecting even small deviations from randomness. The experimental analysis was
      applied to the study of the spatial distribution of apopototic structures in
      malignant neoplastic tissue. It showed that the apopototic cells and bodies are
      characterized by a complex spatial pattern, and aggregate closely.

PMID- 9012572
TI  - Incorporation of the Arden Syntax within the reimplementation of a closed-loop
      decision support system.
AB  - The initial implementation of a clinical decision support system, although
      extremely successful and popular with users, suffered from response time and
      operational support difficulties. As part of the redesign of the system, which
      uses closed-loop rules to propose laboratory and other investigations, the
      decision was taken to move to Arden Syntax for the expression of such rules,
      although in some areas the current standard was felt to be either inadequate or
      inelegant. Such limitations have been overcome by the development of local
      extensions to the Arden Syntax, which are described and where appropriate
      proposed as possible enhancements of the standard. The use of common UNIX tools
      in the creation of a compiler which converts Arden Medical Logic Modules to M
      (MUMPS) code is also discussed.

PMID- 9012573
TI  - Guillain-Barre syndrome.
AB  - The leading cause of acute neuromuscular weakness in the developed world is
      Guillain-Barre syndrome (GBS). Mortality rates vary widely. This article
      discusses the care and management of patients with GBS, with an emphasis on those
      patients who require admission to an intensive care unit.

PMID- 9012574
TI  - Status epilepticus.
AB  - Generalised convulsive status epilepticus is a medical emergency. Knowledge of
      the pathophysiology of status epilepticus and the pharmacology of the medications
      used to treat it allow one to devise a rational protocol for management.
      Anticipation of medical complications facilitates intervention when required.
      Prognosis depends largely on the underlying causes.

PMID- 9012575
TI  - Nutritional management of the critically ill neurologic patient.
AB  - To summarize, the event of severe neurologic injury results in significant
      metabolic changes. These changes cause increased requirements for protein and
      nonprotein calories, micronutrients, and small bowel feedings or TPN. Early
      feeding has been shown to improve survival. Therefore, every effort should be
      made to provide aggressive nutritional support within the first 72 hours after
      injury. Specific guidelines are as follows: Provide full-strength, full-rate
      feedings within 72 hours. Provide enteral nutrients via nasojejunal or
      percutaneous endoscopic jejunostomy feeding tube if access is available; attempt
      gastric feedings if not. Provide TPN within 48 hours if enteral access is not
      available and begin enteral feeding as soon as possible. Provide 2 to 2.3 g
      protein/kg/d if renal function is normal. Provide 40% to 70% above basal needs as
      total calories, with 30% to 40% of calories as lipid to minimize hyperglycemia.
      Provide protein as small peptides to improve tolerance, absorption, utilization,
      and gut integrity. Provide a lipid source with 50% to 70% medium-chain
      triglycerides and an omega-6 to omega-3 ratio of 2:1 to 8:1 to minimize negative
      effects of omega-6 fatty acids and provide an easily absorbed and utilized source
      of lipid.

PMID- 9012576
TI  - Monitoring of cerebral hemodynamics with jugular bulb catheters.
AB  - Jugular venous oxygen saturation (SjvO2) monitoring is useful for detecting
      episodes of cerebral hypoxia/ischemia in patients with head injury, patients
      undergoing neurosurgical procedures, and patients undergoing cardiopulmonary
      bypass. The use of SjvO2 monitoring can direct the treatment of ischemic episodes
      and identify the optimal level of cerebral perfusion pressure and PCO2 for the
      individual patient.

PMID- 9012577
TI  - Transcranial Doppler ultrasonography in the neurocritical care unit.
AB  - TCD ultrasonography is a noninvasive means to study the cerebral vasculature. By
      varying the depth and angle of insonation of a pulsed sound wave, the direction
      and velocity profile of the cerebral arteries can be ascertained. This can be
      used to identify areas of focal stenosis and increased resistance and to estimate
      the adequacy of cerebral flow. TCD ultrasonography commonly is used in SAH to
      detect cerebral vasospasm. Many centers interpret rising velocities as increasing
      vessel narrowing and initiate medical strategies based on these values. TCD use
      in head trauma is less clearly defined. TCD ultrasonography is considered an
      acceptable confirmatory test for the determination of brain death. TCD
      ultrasonography is capable of studying dynamic cerebrovascular processes. By
      being able to determine vessel patency, TCD may become a useful adjuvant to
      thrombolytic therapy. Continuous monitoring of flow velocities and profiles along
      with testing to cerebrovascular reserve promises to be a future active area of
      research.

PMID- 9012578
TI  - Osmotherapy. Basic concepts and controversies.
AB  - Osmotherapy with compounds such as mannitol has become a mainstay of neurologic
      and neurosurgical intensive care. Elevated intracranial pressure is the most
      common indication. A substantive debate remains as to the appropriate timing of
      administration and the optimal fluid management protocol, and experts disagree
      about the clinically relevant mechanisms of action of osmotic diuretics. This
      article briefly summarizes the basic literature on the physical actions of
      mannitol, addresses commonly asked questions, and highlights some of the
      controversies that arise at the bedside.

PMID- 9012579
TI  - Management of hypertension in acute intracerebral hemorrhage.
AB  - Hypertension commonly occurs in the acute period following spontaneous
      intracerebral hemorrhage. Management of this hypertension is controversial. Some
      advocate lowering blood pressure to reduce the risk of bleeding, edema formation,
      and systemic hypertensive complications, whereas others advocate allowing blood
      pressure to run its natural course as a protective measure against cerebral
      ischemia. This article reviews the pertinent clinical and experimental data
      regarding these issues and briefly discusses the use of antihypertensive agents
      commonly administered in this setting.

PMID- 9012580
TI  - The use of hyperventilation and its impact on cerebral ischemia in the treatment
      of traumatic brain injury.
AB  - Traumatic brain injury is a common occurrence in the United States, leading to
      approximately 190,000 deaths or long-term disabilities. Following the primary
      insult, secondary disturbances in cerebral blood flow (CBF) and metabolism may
      have deleterious effects on potentially viable neurons. Recent studies evaluating
      CBF immediately following head injury have revealed flows low enough to produce
      cerebral ischemia. Hyperventilation is used routinely to lower suspected
      increased intracranial pressure (ICP). Aggressive hyperventilation produces a
      marked reduction in CBF, which may give rise to or exacerbate cerebral ischemia,
      thus enhancing rather than reducing secondary injury. This article reviews the
      role of hyperventilation in the treatment of increased ICP and its impact on
      cerebral ischemia following traumatic brain injury.

PMID- 9012581
TI  - Intravenous agents and intraoperative neuroprotection. Beyond barbiturates.
AB  - The authors discuss the role of intravenous anesthetic agents in brain
      protection. The newer intravenous anesthetics, etomidate and propofol, have been
      proposed as neuroprotective agents. Thiopental remains the drug of choice,
      however, for use prior to intraoperative ischemic events. The anesthetic ketamine
      presents surprising similarities to other N-methyl-D-aspartate receptor
      inhibitors, but remains controversial in its use in neurologically compromised
      patients.

PMID- 9012582
TI  - Thrombolytic therapy in neurointensive care.
AB  - Thrombolytic therapy has been studied in acute ischemic stroke, intracranial
      hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and sagittal
      sinus thrombosis. This form of therapy has an evolving role in contemporary
      neurologic practice, and increased investigational fervor will ensure more
      exacting therapeutic alternatives for stroke victims in the future.

PMID- 9012583
TI  - Adoptive CD8+ T-cell immunotherapy of AIDS patients with Kaposi's sarcoma.
AB  - This article reviews published and original findings from two clinical trials of
      adoptive CD8+ T-cell immunotherapy of patients with acquired immunodeficiency
      syndrome (AIDS) and Kaposi's sarcoma (KS). In the first trial, AIDS patients with
      either KS or oral hairy leukoplakia (OHL) received five rounds of reinfusions of
      10(8)-10(10) ex vivo expanded and activated autologous CD8+ T cells. Recombinant
      interleukin-2 (rIL-2) was coadministered only with the fifth and final infusion.
      Improvement, and in some cases, resolution of OHL, KS, and candidiasis was
      observed with no side effects. The observation that clinical improvement of KS
      was more pronounced when reinfusion of CD8+ T cells was followed by rIL-2
      infusion led to a second clinical trial designed to examine the effect of
      repeated infusions of autologous CD8+ T cells with concomitant rIL-2
      administration in the treatment of AIDS-related KS. Improvement of KS status was
      observed in four out of the eight patients studied (three partial and one
      complete response). The CD8+ T-cell immunotherapy protocol also provided the
      opportunity to comparatively study CD8+ T-cell-associated genetic programs.
      Baseline expression patterns of soluble and surface immune markers by CD8+ T
      cells from AIDS patients and uninfected controls were predominantly of the type 1
      type and differed mainly at a quantitative or kinetic level. Deficiencies in
      immune mediator expression by CD8+ T cells from AIDS patients tended to dissipate
      with progression through the protocol. Findings are discussed in the context of
      current knowledge and therapeutic implications of CD8+ T-cell function in AIDS
      and neoplasia.

PMID- 9012584
TI  - Human epithelial cells immortalized by human papilloma viruses.
AB  - Human papillomaviruses (HPVs) are small DNA viruses capable of inducing
      proliferation of epithelial cells in the natural hosts. The etiologic association
      between HPV and many forms of human cancer, especially squamous tumors of the
      anogenital region, has been generally recognized. Human epithelial cells
      transfected by high-risk-type HPV DNA can overcome apoptosis and become
      immortalized, but they are not capable of anchorage-independent growth or
      tumorigenic in nude mice, suggesting that they are premalignant and not malignant
      cells. These cells, due to their genetic instability, are liable to progress to
      anchorage-independent growth and tumorigenicity following subsequent genetic and
      epigenetic events. On the other hand, because immortalized epithelial cells
      represent an initial step in the multistep model of human carcinogenesis in
      vitro, they are useful in studies on the regulation by environment factors.
      Immortalized epithelial cells differ from normal epithelial and malignant
      carcinoma cells, in their response to various cytokines and growth factors, but
      their response is more like that of normal cells than of malignant cells.
      Understanding these processes may help design new therapeutic strategies to
      control tumor growth.

PMID- 9012585
TI  - The Syrian hamster embryo (SHE) cell transformation system: a biologically
      relevant in vitro model--with carcinogen predicting capabilities--of in vivo
      multistage neoplastic transformation.
AB  - Neoplastic transformation is a multistep process that can be modeled in vitro
      using Syrian hamster embryo (SHE) cells. SHE cells multistage transformation
      involves several intermediate stages, including morphological transformation,
      immortality, acquisition of tumorigenicity, and malignant progression. Analysis
      of the molecular alterations that occur at each stage indicated that
      morphological transformation results from both carcinogen-induced irreversible
      chromosomal/genetic mutations and reversible genetic events, including altered
      DNA methylation. Morphological transformation results from a block in the
      cellular differentiation of progenitor and determined stem-like cells in the SHE
      cell population via alternation in the expression of the H19 tumor suppressor
      gene and other genes. Immortality results from genetic mutations in growth factor
      responsiveness, including loss of growth suppression by TGF beta and autocrine
      growth factor production, and genomic stability, resulting in genomic instability
      and an increased mutation rate. Acquisition of tumorigenicity involves loss of
      tumor suppressor gene function, altered mitogenic signal transduction, mutation
      of oncogenes, acquisition of anchorage independent growth, and chromosomal
      aberrations. Malignant progression is associated with alterations in
      extracellular matrix growth characteristics, alterations in cytoskeleton
      structure, elevated fibrinolytic activity, secretion of proteases, and changes in
      extracellular matrix protein secretion. Together, these changes model the
      alterations observed during in vivo neoplastic transformation and possibly
      explain why the SHE assay, as a carcinogen screening tool, is able to identify
      carcinogens with a 80 to 85% accuracy.

PMID- 9012586
TI  - Genetic, epigenetic, dysgenetic, and non-genetic mechanisms in tumorigenesis.
AB  - A not yet understood phenomenon in carcinogenesis is the enormous difference in
      cancer susceptibility of cells from different species and of cells from
      individuals within the same species but with different age. Reviewing of the
      literature points to the promotion phase as the key for this difference. The
      essence of promotion appears to be a profound switch in the cell functions that
      enable cells to respond to stresses such as those caused by wounds and infection
      (cell activation). It was suggested that this switch involves an increase in the
      life span of the cells which, in turn, may predispose them to immortalization. A
      relationship of this switch with the onset of genetic instability was suggested,
      but it is not clear whether genetic instability is inherent to this switch or due
      to an incorrect performance of either switching on or switching off the response.
      The cause of species and age-specific differences in cancer susceptibility has
      therefore been sought in species and age-specific differences on the regulatory
      control of cell activation, an area that is still largely a black box.

PMID- 9012587
TI  - T lymphocytes and their cytokines in human immunodeficiency virus (HIV)
      infection: implications for associated neoplasias.
AB  - Infection with the human immunodeficiency virus (HIV) results in gradual
      immunosuppression due to the loss of CD4+ T cells. In the wake of immune system
      breakdown, infected individuals may acquire multiple opportunistic infections and
      develop certain malignancies which ultimately account for the vast majority of
      deaths in these persons. A limited number of malignancies are directly associated
      with HIV infection and suggest a common tie between these tumors. Inappropriate
      immune surveillance resulting in insufficient inhibition of virus replication and
      inadequate control of the growth of transformed cells may contribute to the
      development of malignancies in HIV-infected individuals. Alternatively,
      malignancies in HIV infection may be the consequence of immune dysregulation.
      Cellular immune responses mediated by antigen-specific cytotoxic T lymphocytes
      (CTL) are of particular importance for immunologic control of viral infections
      and substantial information has been gathered about theses cells in HIV
      infection. The goal of this review is therefore to summarize recent findings
      regarding the cellular immune response to HIV with a particular focus on
      cytokines released by HIV-specific CTL.

PMID- 9012588
TI  - Genotype-phenotype correlations at the adenomatous polyposis coli (APC) gene.
AB  - Germline mutations at the adenomatous polyposis (APC) gene are responsible for
      familial adenomatous polyposis (FAP), an inherited condition that predisposes to
      the development of hundreds to thousands benign adenomas in the colorectum. If
      not surgically removed, colorectal adenomas inevitably progress into malignant
      adenocarcinomas. To date, more than 450 germline mutations have been described at
      the APC gene, allowing the establishment of genotype-phenotype correlations
      between the site and type of the molecular defects and their morbid consequences.
      However, the function of the APC protein and its role in intestinal tumorigenesis
      are still elusive. Somatic mutations in the APC gene have also been found in the
      majority of early sporadic adenomas with similar frequencies as those reported in
      the more advanced colorectal tumors, clearly indicating that it represents an
      important determinant in the pathogenesis of this common cancer. Therefore,
      studies on the normal function of APC and the mechanisms by which its tumorigenic
      mutations lead to the development of cancer would have practical (i.e., clinical)
      as well as theoretical relevance. Here, we review the current literature on the
      relationship between APC mutations and their phenotypic consequences, with
      particular regard of the implications for the understanding of the function of
      this gene in homeostasis and tumorigenesis.

PMID- 9012589
TI  - Structure and pathophysiology of the erythrocyte membrane-associated Paul-Bunnell
      heterophile antibody determinant in Epstein-Barr virus-associated disease.
AB  - Epstein-Barr virus (EBV), which was first isolated by Epstein, Barr, and Achong
      (1964) from a cultured Burkitt's lymphoma lymphoblast cell line, is the
      etiological agent for infections mononucleosis (IM), polyclonal oligoclonal
      lymphomas associated with primary and acquired immunodeficiencies, and the
      complications of X-linked lymphoproliferative syndrome (XLP) (Cantani and
      Mastrantoni, 1989; Englund, 1988; Ernberg et al., 1990; Jones and Straus, 1987;
      Okano et al., 1988; Purtilo et al., 1981; Shearer et al., 1985; Wilmes and Wolf,
      1989). EBV also contributes to the pathogenesis of Burkitt's lymphoma (Frizzera,
      1987; Harrington et al., 1988; Henle et al., 1968; Purtilo et al., 1981; Rowe et
      al., 1986; Saemundsen et al., 1981) and nasopharyngeal cancer (Pearson et al.,
      1984). Furthermore, people who have had IM have higher rates of subsequent
      development of malignant lymphoproliferative disorders (Abo et at., 1982; Snydman
      et al., 1982) and Hodgkin's disease (Green et al., 1979; Mueller, 1987; Poppema
      et al., 1985; Weiss et al., 1989), while patents with XLP have a higher incidence
      of non-Hodgkin's malignant lymphoma (Harrington et at., 1987). The precise role
      of EBV in these diseases is not well understood. Nonetheless, it is known that
      EBV infection triggers the formation of heterophile antibodies that, for many
      decades, have formed the basis for serologic diagnosis of IM. In this review, we
      discuss the discovery, species variation, and structure of the erythrocyte
      membrane-associated Paul-Bunnell (PB) heterophile antibody determinant, its
      implications to IM diagnosis, and its potential contribution to defective immune
      surveillance and associated uncontrolled proliferation of EBV-infected cells.

PMID- 9012590
TI  - Effects of benzalkonium salts on eukaryotic and microbial G-protein-mediated
      processes and surface membranes.
AB  - Benzalkonium salts comprise a group of positively charged surface-active
      alkylamine biocides with the general formula alkyldimethylbenzylammonium chloride
      or bromide. They interact with guanine nucleotide triphosphate-binding proteins
      (G proteins), thereby affecting signal transduction in a variety of cell types
      and processes. The present report reviews the known and potential basic science
      research and clinical applications and manifestations of benzalkonium salts.
      Benzalkonium salts have antiproliferative effects on a variety of cells through G
      protein-dependent pathways, affect cytokine gene expression, and are also
      effective bactericidal, fungicidal, and virucidal agents with multisite (direct
      and immunologically-mediated) inhibitory activity against many pathogens,
      including the human immunodeficiency virus (HIV), papillomavirus, and
      herpesviruses. Therefore, benzalkonium salts not only appear to be effective as
      disinfectants and spermicides but may also prove useful in the prevention and
      treatment of neoplasias and other disease, particularly those linked to viruses
      and originating at the skin or mucosal surface.

PMID- 9012591
TI  - Of mice and men: a critical reappraisal of the two-stage theory of
      carcinogenesis.
AB  - The two-stage theory of carcinogenesis attempts to reduce a very complex set of
      data to simple terms: it defines a carcinogen as "an agent that causes a neoplasm
      by a two-step process involving initiation and promotion". The theory has
      achieved the status of a paradigm, and all new experiments carried out by two
      stage supporters are designed according to its premises and therefore will eo
      ipso tend to confirm it. Popper's dictum that any scientific hypothesis should be
      put to the strongest test, namely, by trying to refute it, has rarely (or never)
      been observed. The two-stage theory was originally based on standard mouse skin
      painting experiments. All the original work is grounded on classic skin
      carcinogenesis, and only later was it extended to also comprise carcinogenesis in
      other organs, thereby becoming a general theory. On the basis of the same
      standard skin painting experiments and in accordance with Popper's dictum, the
      present review shows how the following generally accepted corollaries of the two
      stage theory have been refuted: initiation must come first in time; in previously
      initiated mouse skin promotion always leads to a synergistic increase in tumor
      crop, whereas complete carcinogens at subthreshold does (regarded as merely
      initiating) have only an additive effect; the reverse experiment is innocuous;
      there is a qualitative difference between the effect of initiators and that of
      promoters; initiators only initiate at low dose levels, but abruptly become
      rather complete carcinogens at higher doses, promotion must take place over a
      long period, and repeated exposure without prolonged intervals is essential; pure
      initiators exist, for example, urethane for the epidermis; pure promoters exist,
      e.g., TPA; skin inflammation and persistent hyperplasia are essential parts of
      promotion; increased levels of the enzyme ODC followed by increasing levels of
      polyamines are casually involved in promotion; the appearance of many dark
      epidermal cells is a sign of promotion and the dark cells are stem cells from
      which tumors arise. Carcinogenesis is a very complicated process characterized
      not only by disturbances in cell cycle control, cell differentiation and/or
      maturation, but also by changes in the normal ability of cells to respect organ
      and tissue boundaries. Infiltrative growth and metastases are the most dangerous
      properties of cancer, and the two-stage theory does not provide an explanation
      for these two most serious aspects of the disease.

PMID- 9012592
TI  - Dietary energy sources and colon cancer risk.
AB  - Because energy-contributing nutrients are highly correlated with total energy,
      the association with colon cancer from energy versus other components of energy
      providing nutrients is often not clear. Dietary data from a population-based case
      control study of colon cancer were analyzed in subjects from California, Utah,
      and Minnesota in 1991-1994 to assess the colon cancer risk associated with
      consumption of energy, fat, protein, and carbohydrate. After adjustment for long
      term physical activity, total energy intake increased risk of colon cancer in men
      (odds ratio = 1.74, 95% confidence interval 1.14-2.67 for highest vs. lowest
      quartile) and in women (odds ratio = 1.70, 95% confidence interval 1.07-2.70).
      Various methods of analysis suggested that intakes of individual sources of
      energy (dietary fat, protein, and carbohydrate) were not associated with colon
      cancer risk after total energy intake was taken into account. People who consumed
      a high-calorie diet that was dense in fiber and calcium appeared to be at lower
      risk than people with the same caloric intake who consumed smaller amounts of
      dietary fiber and calcium. Individuals with a first-degree relative with
      colorectal cancer, especially those diagnosed at a younger age, were at a greater
      risk from a diet high in energy than were individuals without a family history of
      colorectal cancer.

PMID- 9012593
TI  - Analysis of current trends in United States mesothelioma incidence.
AB  - Mesothelioma incidence often is interpreted as an index of past exposure to
      airborne asbestos. The mesothelioma rate for US males exhibits an increasing
      trend throughout the 1970s and early 1980s. The trend has been attributed to
      occupational exposure in the shipbuilding industry during World War II, in
      manufacturing, and in building construction. Incidence data (1973-1992) from the
      Surveillance, Epidemiology, and End Results Program were used to investigate
      current trends in age-adjusted and age-specific mesothelioma rates. An age and
      birth-cohort model was used to project both lifetime probabilities of
      mesothelioma by cohort and the annual number of cases expected over the next 70
      years. The current trend in female rates is flat (age-adjusted rate = 0.30 per
      100,000). The estimated lifetime risk for females is 2.5 x 10(-4), independent of
      birth cohort. The projected average annual number of female cases is 500. For
      males, the age-adjusted mesothelioma rate is increasing solely due to the age
      group 75 years and over, albeit at a declining growth rate. Lifetime risk for
      males peaks at 2 x 10(-3) for the 1925-1929 birth cohort, then decreases to 5 x
      10(-4) for the 1955-1959 birth cohort. The pattern of rates reflected in the age
      and birth-cohort model suggests a peak in the annual number of mesothelioma cases
      for males at 2,300 before the year 2000. The number of male cases then will drop
      during the next 50-60 years toward 500. These trends mirror the US trend in raw
      asbestos consumption and a reduction in workplace airborne asbestos levels.

PMID- 9012594
TI  - Electromagnetic fields and cancer in children residing near Norwegian high
      voltage power lines.
AB  - The aim of the nested case-control study reported here was to test the hypothesis
      that exposure to electromagnetic fields of the type generated by high-voltage
      power lines increases the incidence of cancer in children aged 0-14 years. The
      study population comprised children who during at least one of the years 1960,
      1970, 1980, 1985, 1987, or 1989 had lived in a census ward crossed by a high
      voltage power line. The cases were diagnosed from 1965 to 1989 and were matched
      to controls by year of birth, sex, and municipality. Exposure to electric and
      magnetic fields was calculated by means of computer programs in which power line
      characteristics and distance were taken into account. No association was found
      between exposure to time-weighted average exposure to magnetic fields and cancer
      at all sites, brain tumors, lymphoma, or leukemia. Cancer at other sites showed
      elevated odds ratios in the two highest exposure categories in some, but not all,
      measures of exposure. This study provides little support for an association
      between children's exposure to magnetic fields and cancer and no support for an
      association between leukemia and such exposure, but no firm conclusions can be
      drawn owing to the small numbers involved.

PMID- 9012595
TI  - Ability of Medicare claims data and cancer registries to identify cancer cases
      and treatment.
AB  - The objective of this study is to compare the ability of Medicare and cancer
      registry data to identify incident cancer cases and initial surgical therapy both
      singly and in combination. Data from the Virginia Cancer Registry (VCR) were
      linked to Medicare claims files (Medical Provider Analysis and Review File
      (MEDPAR)) for Virginia residents aged 65 years and over with breast, colorectal,
      lung, or prostate cancer diagnosed between 1986 and 1989. MEDPAR found 73-83% of
      cancer cases identified by VCR. Factors significantly associated with MEDPAR
      missing a case that was reported to VCR included younger age, male gender, living
      in an urban area, higher social class, in situ disease, and lack of cancer
      treatment. A total of 70-82% of cancer cases identified through Medicare claims
      were reported to the VCR. Older age, female gender, nonwhite race, comorbid
      conditions, no surgical procedures, multiple cancer admissions, and the position
      of the cancer diagnostic code on the MEDPAR record were factors significantly
      related to being missed by the VCR. The rate of capturing initial surgical
      therapies was similar to that of identifying cases. Combining information from
      VCR and MEDPAR resulted in increasing sensitivity for identifying incident cases
      to 92-97%. Using combined data from independent sources may improve reporting,
      increase the accuracy of cancer incidence estimates, and provide an opportunity
      to identify reasons for missing data.

PMID- 9012596
TI  - Racial differences in sarcoidosis incidence: a 5-year study in a health
      maintenance organization.
AB  - Reports of racial differences in the incidence of sarcoidosis, a granulomatous
      disorder of unknown etiology, are primarily based on studies of military and
      veteran populations. To determine racial differences in sarcoidosis incidence in
      a metropolitan population the authors conducted a study of newly diagnosed cases
      that occurred between 1990 and 1994 among members of the Health Alliance Plan
      health maintenance organization in Detroit, Michigan. The study population was
      racially heterogeneous, was limited to individuals aged 20-69 years, and
      comprised about 5% of the Detroit metropolitan area population in that age group.
      Annual age-adjusted incidence, in number of new cases per 100,000, was highest in
      African-American females (39.1 cases). The next highest incidence was found in
      African-American males (29.8 cases), followed by Caucasian females (12.1) and
      Caucasian males (9.6). African-American females aged 30-39 years were at the
      greatest risk, with an annual incidence of 107/100,000. Overall, African
      Americans had about a threefold higher age-adjusted annual incidence
      (35.5/100,000) compared with Caucasians (10.9/100,000). Additional adjustment for
      sex, area of residence, and year of study resulted in 3.8-fold greater risk for
      African Americans compared with Caucasians. This study further confirmed the
      higher incidence of sarcoidosis in African Americans compared with Caucasians,
      but the racial difference was lower than previously reported. The results should
      be more generalizable than previous studies done with select populations and
      should serve as a useful frame of reference for future epidemiologic research of
      sarcoidosis.

PMID- 9012597
TI  - Hormone replacement therapy, reproductive factors, and cataract. The Blue
      Mountains Eye Study.
AB  - The relation between estrogen (endogenous and exogenous) and cataract is unclear,
      with one large population-based study recently suggesting a protective effect of
      estrogen replacement therapy. The study reported in this paper, the Blue
      Mountains Eye Study, was conducted in Australia in 1992-1993 and involved 2,072
      women aged 49-97 years. Subjects were recruited from a defined geographic area;
      the participation rate was 83 percent. Eye examination included photographs of
      the lens, which were graded for presence and severity of cortical, nuclear, and
      posterior subcapsular cataracts. Later age at menarche was associated with
      increased prevalence of all three types of cataract, but there were no
      associations with age at menopause, number of children, or use of the oral
      contraceptive pill. Among all women, there was no association between hormone
      replacement therapy and cataract. However, current users of hormone replacement
      therapy aged 65 years and over, among whom the duration of use was likely to have
      been longer than in younger current users, had lower prevalence of cortical
      cataract than did never users; the odds ratio adjusted for numerous potential
      confounders was 0.4 (95 percent confidence interval 0.2-0.8). The prevalence of
      posterior subcapsular cataract was increased in current users of hormone
      replacement therapy who had had a nonsurgical menopause; the adjusted odds ratio
      was 2.1 (95 percent confidence interval 1.1-4.1). The results of this study
      support the hypothesis that estrogen and/or progestin may be involved in cataract
      development. The effect of hormone replacement therapy on the lens needs to be
      evaluated in the laboratory and in further observational epidemiologic studies.

PMID- 9012598
TI  - Effects of maternal cigarette smoking and alcohol consumption on blood lead
      levels of newborns.
AB  - The purpose of this study was to evaluate the effect of cigarette smoking (active
      and passive exposure) and alcohol consumption during pregnancy on cord blood lead
      levels. In 1990, a survey was conducted in two hospitals in Quebec City, Quebec,
      Canada, a white-collar agglomeration. The sample included 430 mothers and their
      newborns. Information on the lifestyles of mothers during pregnancy was obtained
      by questionnaire. Cord blood lead concentrations were measured by atomic
      absorption spectrophotometry. A dose-response relation was found between
      cigarette smoking and alcohol consumption of mothers and cord blood lead levels.
      An average increase of about 15 percent (0.013 mumol/liter) in cord blood lead
      levels was estimated for every 10 cigarettes smoked per day. Mean blood lead
      levels in babies whose mothers did not smoke during pregnancy but who drank
      alcohol moderately was 17 percent higher than those of nonsmoking mothers who
      abstained from alcohol intake. Multivariate analyses revealed that both cigarette
      smoking and alcohol intake make significant and independent contributions to cord
      blood lead concentrations. Lifestyles of pregnant women thus appear to play an
      important role in the prenatal lead exposure of newborns. Because of the
      potential effects of lead exposure on pregnancy outcomes, our study provides
      further arguments to support public health advisories concerning the harmful
      effect of smoking and drinking alcohol during pregnancy.

PMID- 9012599
TI  - Ozone, suspended particulates, and daily mortality in Mexico City.
AB  - To investigate acute, irreversible effects of exposure to ozone and other air
      pollutants, the authors examined daily death counts in relation to air pollution
      levels in Mexico City during 1990-1992. When considered singly in Poisson
      regression models accounting for periodic effects, the rate ratio for total
      mortality associated with a 100-ppb increment in 1-hour maximum ozone
      concentration was 1.024 (95% confidence interval (CI) 1.011-1.039). Measures of
      average ozone concentration were somewhat more strongly related to mortality. The
      rate ratio was 1.024 (95% CI 0.984-1.062) per 100 ppb for sulfur dioxide and
      1.050 (95% CI 1.030-1.067) per 100 micrograms/m3 for total suspended
      particulates. However, when all three pollutants were considered simultaneously,
      only total suspended particulates remained associated with mortality, indicating
      excess mortality of 6% per 100 micrograms/m3 (rate ratio = 1.058, 95% CI 1.033
      1.083), consistent with observations in other cities in the United States and
      Europe. The authors found no independent effect of ozone, but it is difficult to
      attribute observed effects to a single pollutant in light of the complexity and
      variability of the mixture to which people are exposed. Nevertheless, particulate
      matter may be a useful indicator of the risk associated with ambient air
      pollution.

PMID- 9012600
TI  - Estrogen replacement therapy and prognosis after first myocardial infarction.
AB  - The effects of estrogen replacement therapy on prognosis in women with
      established coronary disease remain uncertain. The authors conducted a
      retrospective cohort study of 726 women (mean age, 66.2 years) who survived first
      myocardial infarction to hospital discharge from 1980 through 1991, while
      enrolled at Group Health Cooperative of Puget Sound in western Washington State.
      Estrogen replacement therapy after myocardial infarction (122 women) was
      ascertained from computerized pharmacy records. Reinfarctions (n = 135) and
      deaths (n = 183) through 1993 were identified, and relative risks were
      calculated. The relative risk for reinfarction associated with current estrogen
      replacement therapy after myocardial infarction, adjusting for age and time since
      infarction, was 0.64 (95% confidence interval (CI) 0.32-1.30), and that for past
      estrogen replacement therapy was 0.90 (95% CI 0.62-1.31). The relative risk for
      all-cause mortality associated with current estrogen replacement therapy was 0.50
      (95% CI 0.25-1.00), and that for past estrogen replacement therapy was 0.79 (95%
      CI 0.56-1.09). While estrogen users were less likely than nonusers to have a
      history of diabetes or congestive heart failure, adjustment for these and
      additional prognostic factors altered risk estimates only slightly. Estrogen
      replacement therapy after first myocardial infarction was not associated with
      increased risk of reinfarction or mortality. This study provides reassurance
      regarding the safety of estrogen replacement therapy after myocardial infarction
      in women.

PMID- 9012602
TI  - Re: "Bayesian estimation of disease prevalence and the parameters of diagnostic
      tests in the absence of a gold standard".

PMID- 9012601
TI  - Construction of composite scales for risk assessment in epidemiology: an
      application to ectopic pregnancy.
AB  - Composite scoring systems that combine information contained in a number of risk
      factors are being used increasingly in clinical practice, planning, and health
      risk appraisal. The authors propose a methodological framework for the
      construction and validation of a composite measurement scale to assess the risk,
      considered as a continuous phenomenon, of developing a particular disease or
      outcome. This framework integrates several statistical methods, especially those
      concerning model fitting, coefficient rounding, and validation strategy. It also
      uses psychometric methods, addressing important measurement properties such as
      measurement level, content and construct validity, and reliability of the
      constructed scale. The proposed framework is illustrated by application to the
      construction of a composite scale for measurement of the risk of ectopic
      pregnancy.

PMID- 9012603
TI  - Re: "Occupational risk factors for prostate cancer: results from a case-control
      study in Montreal, Quebec, Canada".

PMID- 9012604
TI  - Management of depression in primary care. Introduction.

PMID- 9012605
TI  - Major depression in the primary care setting.
AB  - This article has provided a brief overview of the prevalence, differential
      diagnosis, and clinical manifestations of depression in the primary care setting.
      While the high prevalence of depression is well documented, another body of
      evidence is accruing that demonstrates that depression not only increases over
      utilization of medical resources, but may worsen the long-term prognosis of
      certain medical conditions such as MI. Evidence also suggests that the diagnostic
      and management skills of primary care physicians--who comprise the "front line"
      and may offer the only line of care for these patients--is in need of
      improvement. This series of articles focusing on the diagnosis and treatment of
      depression in primary care will hopefully contribute to that effort.

PMID- 9012606
TI  - Making the diagnosis of depression in the primary care setting.
AB  - Making the diagnosis of depression in the primary care setting represents a
      challenge and an opportunity. With the numerous cultural, administrative, social,
      and financial obstacles to the assessment and management of mental disorders in
      primary care, it is a small wonder that so much treatment of depression actually
      does occur. However, much depression is missed, and even when the diagnosis is
      not missed, many depressed patients do not receive adequate treatment. This
      article reviews the different depressive conditions of importance that present in
      primary care, discusses complexities of differential diagnosis, and underscores
      the importance of the medical interview itself for eliciting relevant data,
      developing rapport, and educating the patient about the key issues of importance
      relevant to the management of depression.

PMID- 9012607
TI  - Management strategies for depression in primary care.

PMID- 9012608
TI  - Update in the pharmacotherapy of depression.

PMID- 9012610
TI  - Management options for refractory depression.

PMID- 9012609
TI  - Office psychotherapy for depression in the primary care setting.
AB  - Effective medical care is founded on an understanding of what a particular
      illness means to a particular patient at a particular time in life. This requires
      a full understanding of the patient's illness dynamics, which inform primary care
      clinicians as to the specific psychological needs to be addressed during the
      course of medical treatment. This is extremely relevant when treating patients
      suffering from depression, either as a primary disorder or concurrent to a
      medical condition. Medical psychotherapy can then be implemented either as a
      supportive or introspective approach and sometimes supplemented with
      pharmacotherapy, if the patient's emotional distress is extreme. This
      comprehensive biopsychosocial regimen is the acceptable medical model if "one is
      to treat the whole patient and not merely characterize the nature of an illness
      and impede biological deterioration."

PMID- 9012611
TI  - Reimbursement issues in the treatment of depression.

PMID- 9012612
TI  - Building partnerships with patients.

PMID- 9012613
TI  - Hypothesis testing and effect size estimation in clinical trials.
AB  - LEARNING OBJECTIVES: This paper provides the reader with an overview of several
      key elements in study planning and analysis. In particular, it highlights the
      differences between significance tests (statistical significance) and effect size
      estimation (clinical significance). DATA SOURCES: This paper focuses on
      methodologic issues, and provides an overview of trends in research. PAPER
      SELECTION: References were selected to provide a cross-section of the approaches
      currently being used. The paper also discusses a number of logical fallacies that
      have been cited as examples in earlier papers on research design. CONCLUSIONS:
      Significance tests are intended solely to address the viability of the null
      hypothesis that a treatment has no effect, and not to estimate the magnitude of
      the treatment effect. Researchers are advised to move away from significance
      tests and to present instead an estimate of effect size bounded by confidence
      intervals. This approach incorporates all the information normally included in a
      test of significance but in a format that highlights the element of interest
      (clinical significance rather than statistical significance). This approach
      should also have an impact on study planning--a study should have enough power to
      reject the null hypothesis and also to yield a precise estimate of the treatment
      effect.

PMID- 9012614
TI  - Anemia in a patient with panhypogammaglobulinemia.

PMID- 9012615
TI  - Ethnic differences in the prevalence of asthma in middle class children.
AB  - BACKGROUND: Studies have shown a higher prevalence of asthma among boys compared
      with girls and in blacks compared with whites, but it has been difficult to
      separate socioeconomic from racial effects because the blacks in the studied
      populations were more likely to have low socioeconomic status. OBJECTIVE: To
      compare the prevalence of asthma in a socioeconomically homogeneous, middle
      class, multiethnic population of schoolchildren. METHODS: Based on a telephone
      survey of all families of third-graders in Southfield, Michigan, we ascertained
      the prevalence of physician-diagnosed asthma and probable undiagnosed asthma. One
      reason Southfield was chosen for study was because the city comprises an
      integrated middle class population with only 4% blacks and 7% whites having
      incomes below federal poverty limits. RESULTS: The lifetime prevalence of asthma
      was 9.5% (12% for blacks and 6% for whites) and higher in boys (14%) than girls
      (5%), a pattern that was reflected in period prevalence estimates. The lifetime
      prevalence of probable undiagnosed asthma was greater in blacks (16.6%) than
      whites (10.8%), with little sex difference. Adjusting for sex and maternal
      education, the prevalence of physician-diagnosed asthma and probable asthma were
      associated independently with black ethnicity. CONCLUSIONS: Our study is unique
      in the similarity of the black and white families' socioeconomic status and
      residence in the same middle class community. Since access to medical care and
      macro-environmental conditions were similar across this study population, our
      results are consistent with the hypothesis that differences in biologic factors
      between blacks and whites and boys and girls play a role in asthma risk.

PMID- 9012616
TI  - Asymptomatic lymphoma associated with elevation of immunoglobulin E.
AB  - BACKGROUND: Elevation of immunoglobulin E (IgE) is rarely detected in patients
      with underlying malignancy. There has been only one report of such a finding in a
      patient with a T cell lymphoma and none to our knowledge in association with a B
      cell lymphoma. OBJECTIVE: To report a patient with elevation of IgE associated
      with a B-cell lineage lymphoma. MATERIAL AND METHODS: Case report and review of
      literature. RESULTS: A 73-year-old woman was found to have elevated IgE (11,766
      IU/mL) in a routine evaluation for rhinitis. No underlying allergic diathesis or
      disease associated with IgE elevation was noted. Because of an abnormal
      lymphocyte profile, an extensive malignancy evaluation was performed which
      revealed a B-cell lymphoma. CONCLUSION: B-cell lineage lymphoma can be associated
      with elevated of IgE and should be included in the differential diagnosis in a
      patient presenting with this finding.

PMID- 9012617
TI  - How many teenagers think they have allergic rhinoconjunctivitis and what they do
      about it.
AB  - OBJECTIVE: A study was made to assess the proportion of 17-year-old students who
      consider themselves to have allergic rhinoconjunctivitis and to find out how they
      treat themselves. METHOD: The study was performed outside the pollen season in
      1993 and 1994 and 5,938 first-year secondary school students in eight different
      cities were asked to answer a questionnaire during class. RESULTS: A total of
      1,458 students (24%) claimed that they suffered from allergic rhinoconjunctivitis
      after being given a description of the disease. Sixty-five percent had had
      symptoms for 3 or more years and most of the sufferers, 71%, had had symptoms
      during the spring and/or summer. In 32% of the sufferers the causative agent was
      unknown. Seventy-six percent (n = 1,103) of the sufferers treated themselves with
      drugs. The most commonly used drugs for a systemic effect were nonsedating
      antihistamines and for a local effect, sodium cromoglycate. Of those who used
      nasal drugs (sodium cromoglycate and/or steroids, n = 545), only 14% used them
      daily, 51% always when having symptoms, and 35% occasionally when having
      symptoms. The reasons for not using nasal sprays daily were inconvenience and
      embarrassment. Twenty-five percent had bought the drug over the counter in 1992,
      the first year when allergy drugs could be purchased without a prescription. The
      use of over-the-counter treatment increased in the following year to 33% (P <
      .05). CONCLUSION: We conclude that many young people perceive themselves as
      having allergic rhinoconjunctivitis and that the treatment can be much improved
      for the group as a whole.

PMID- 9012618
TI  - Hot dog vapor-induced status asthmaticus.
AB  - BACKGROUND: Asthma induced by the inhalation of food vapors is unusual and
      indicative of extreme allergy. Identification of the specific cause and
      subsequent avoidance is essential. METHODS: We report a patient with asthma who
      had status asthmaticus following inhalation of boiling hot dog vapors. Prick skin
      tests were performed to various ingredients of the offending hot dog including
      chicken, pork, potato, and the aeroallergens. RESULTS: Prick skin tests reacted
      strongly to chicken and mildly to pork and potato. There was no reaction to
      aeroallergens. Our patient has not had any acute asthma after avoiding eating and
      exposure to chicken and hot dog vapors. CONCLUSIONS: Exquisite allergy to chicken
      was responsible for acute asthma.

PMID- 9012619
TI  - Occupational allergic rhinoconjunctivitis and asthma due to fennel seed.
AB  - BACKGROUND: A patient with complaints of rhinitis and asthma occurring at work
      presented for consultation. OBJECTIVES: To evaluate the role of the foods and
      spices with which he worked, in the causation of his complaints, and to evaluate
      his immune reactivity to these materials. METHODS: Allergy skin testing and in
      vitro RAST assays were carried out. After demonstrating specific reactivity to
      fennel, SDS-PAGE electrophoreses was carried out. RESULTS: Positive skin tests to
      grass, ragweed, and freshly prepared fennel seed were found. Serum IgE antibodies
      to fennel were quite high. Immunoblotting studies showed reactions to two
      components in fennel extract as well as to components in mugwort, paprika, short
      ragweed and black pepper. CONCLUSION: This case of occupational rhinitis and
      asthma in an atopic individual involves sensitivity to unique allergens in
      fennel, with molecular weights of 67 to 75 KD.

PMID- 9012620
TI  - Prevalence of latex sensitization in a hospital employee population.
AB  - BACKGROUND: Immediate-type allergic reactions to latex products have become
      increasingly recognized in hospital workers. OBJECTIVE: This study was designed
      to assess the prevalence of latex sensitization by skin testing and specific IgE
      testing in a group of hospital employees and compare these with each subject's
      self-reported allergic history. METHODS: Volunteers were recruited from selected
      departments. Each was tested with epicutaneous skin test with latex glove extract
      and commercial environmental allergens, had blood drawn for latex-specific IgE
      testing (AlaSTAT brand of ELISA), and was given a questionnaire for general and
      latex allergy history. RESULTS: There were 135 participants. Eleven (8.2% of
      sample, 95% confidence interval 3.4% to 13.0%) were skin test positive for latex
      reagent, and seven of these (5.2% of sample) reported allergic symptoms to latex
      contact. Testing for latex-specific IgE (ELISA) showed 6.7% with class II or
      higher reaction. There was high correlation of the two tests, with ELISA showing
      a sensitivity of 63.6% and a specificity of 98.4% with reference to skin testing.
      In this sample, 16% reported some upper respiratory symptoms in association with
      latex contact, although only one-third of this group was skin test positive. Past
      history of allergic or atopic disease was poorly predictive of skin or blood test
      reactivity. A reaction to a greater number of environmental allergens was
      associated with positive latex skin test reactivity. CONCLUSION: Testing for
      latex sensitivity in this hospital sample revealed more than 5% of workers
      developed clinical allergies to latex and continued to remain occupationally in
      contact with latex. In vitro testing is a potential substitute for the more
      technically difficult skin testing.

PMID- 9012622
TI  - Prevalence of human seminal plasma hypersensitivity among symptomatic women.
AB  - BACKGROUND: Experience with human seminal plasma hypersensitivity in the last
      decade has led to increased physician awareness of symptoms consistent with human
      seminal plasma sensitization in women. Incidence and prevalence of human seminal
      plasma hypersensitivity in women are unknown. OBJECTIVE: A questionnaire survey
      was distributed to determine the prevalence of human seminal plasma
      hypersensitivity among a population of women suspected of having this disorder.
      METHODS: A questionnaire designed to elicit age, symptoms, duration of symptoms,
      number of sexual partners, time to onset of symptoms after first human seminal
      plasma exposure, onset of symptoms after first intercourse, recent gynecologic
      procedures, history of atopy, vaginitis, food or drug allergy and family history
      of atopy was distributed to 1,073 women who suspected they had symptoms
      consistent with human seminal plasma hypersensitivity. Women were considered
      "possible" for human seminal plasma hypersensitivity if they reported two or more
      symptoms consistent with localized or systemic human seminal plasma
      hypersensitivity. Women were considered "probable" for disease if they fulfilled
      the "ultimate criterion" defined as complete prevention of symptoms with a
      condom. Women with "possible" localized or systemic human seminal plasma
      hypersensitivity who had persistent symptoms despite use of a condom served as
      cohort control groups. RESULTS: Two-hundred sixty-six women reported symptoms
      "possible" for human seminal plasma hypersensitivity (88 localized and 178
      systemic). When the "ultimate criterion" was applied, 130 (46 localized and 84
      systemic) of the 266 women were identified as having "probable" human seminal
      plasma hypersensitivity. The responses to most of the questions from each group
      were very similar. A significantly shorter time interval to symptom onset after
      initial human seminal plasma exposure was more common for women with "probable"
      localized human seminal plasma hypersensitivity compared with their cohort
      control group (49 months versus 108 months; P < .02) whereas a significantly
      increased number of women with "probable" systemic human seminal hypersensitivity
      gave positive food allergy histories compared with their cohort control group (31
      versus 20; P < .05). Atopy did not appear to be a risk factor for human seminal
      plasma hypersensitivity. CONCLUSIONS: Evaluation of women with symptoms
      suggestive of human seminal plasma hypersensitivity using a validated
      questionnaire indicates that this disorder is more common than previously
      recognized.

PMID- 9012621
TI  - Plasma IgE levels, activation marker expression, and cytokine production in non
      atopic individuals.
AB  - BACKGROUND: Since human IgE serum levels are very low compared with the other
      immunoglobulin isotypes, most studies have examined the regulation of IgE
      production in severely atopic individuals where serum IgE levels are increased.
      Since atopy is a pathologic consequence of increased IgE production, this disease
      state could have other influences that result in abnormal expression of these
      parameters and may not reflect normal IgE regulatory mechanisms. OBJECTIVE: To
      study nonatopic individuals to examine the expression of IgE regulatory cytokines
      as well as additional cell surface activation markers in relation to serum IgE
      levels. METHOD: We selected ten individuals at both the lower and higher end of a
      spectrum of plasma IgE concentrations from 29 nonatopic individuals and compared
      the differences in cytokine and activation marker expression in relation to IgE
      production. RESULTS: We found that even upon extensive examination of activation
      markers on T, B, and NK cell subsets, there are no significant differences in the
      cell populations or surface marker expression between the high IgE and low IgE
      groups. Messenger RNA expression in peripheral blood mononuclear cells (PBMCs) of
      the cytokines IL-4 and IL-6 was significantly higher, whereas IL-10 was lower in
      the high IgE group. In addition upon in vitro polyclonal stimulation of
      peripheral blood mononuclear cells, individuals of the high IgE group produced
      lower levels of IL-2, IFN gamma and IL-10 compared to the low IgE donors.
      CONCLUSION: Since our results differ from studies using atopic individuals, this
      study demonstrates the importance of using nonatopic individuals for examining
      associations between various immune parameters and IgE.

PMID- 9012623
TI  - Albuterol via Turbuhaler versus albuterol via pressurized metered-dose inhaler in
      asthma.
AB  - BACKGROUND: Inhaled albuterol is most commonly self-administered by patients
      using a pressurized metered-dose inhaler (pMDI) but patients often have
      difficulty using the device. Dry powder devices such as the multi-dose,
      inspiratory flow driven inhaler (Turbuhaler) are often better handled by
      patients. OBJECTIVE: We sought to compare the efficacy and tolerability of 100
      micrograms of albuterol delivered by a multi-dose, inspiratory flow driven
      inhaler (Turbuhaler) to a standard dose (200 micrograms) delivered by a pMDI
      (Ventolin) in chronic reversible obstructive airways disease. METHOD: In 6
      centers, we studied 37 adults [19 men and 18 women, mean age 39 +/- 12 years;
      mean baseline forced expiratory volume in one second (FEV1) 72 +/- 13% (%
      predicted)] with stable but symptomatic reversible obstructive airways disease as
      demonstrated by 15% or greater increase in FEV1 following two puffs (200
      micrograms) albuterol by pMDI. The crossover design comprised a 1-week run-in and
      two 2-week treatment periods separated by a 1-week washout. At the start and end
      of each treatment period, FEV1 was measured at the clinic. Patients self
      administered albuterol 100 micrograms (2 x 50 micrograms) via Turbuhaler or 200
      micrograms (2 x 100 micrograms) via pMDI in a double-blind fashion four times
      daily. Morning and evening peak expiratory flow (PEF) was noted daily. All non
      study bronchodilators were withheld while open-label albuterol pMDI was offered
      for rescue. RESULTS: Of the 37 patients, 30 used inhaled steroids in constant
      doses throughout the study, one used inhaled cromoglycate and six used no anti
      inflammatory therapy. There was no difference between treatment periods in
      morning PEF, diurnal fluctuation in PEF, increase in PEF following study drug,
      baseline FEV1 and FEV1 increase following study drug. Although there was no
      difference in symptom scores between treatments, the use of rescue beta 2-agonist
      was slightly but significantly higher during the Turbuhaler treatment period
      (1.34 versus 1.08 inhalations/ day, P = .04). Compliance with study drug was
      slightly but significantly lower during the Turbuhaler treatment period (87
      versus 95%) such that the total number of beta 2-agonist puffs inhaled (scheduled
      plus rescue) was similar between treatments. With regard to adverse events, both
      treatments were well tolerated. CONCLUSIONS: These results suggest that the
      efficacy and tolerability of albuterol 100 micrograms qid inhaled via Turbuhaler
      is similar to albuterol 200 micrograms qid, inhaled via pMDI in stable reversible
      obstructive airways disease.

PMID- 9012624
TI  - EMLA cream for pain reduction in diagnostic allergy skin testing: effects on
      wheal and flare responses.
AB  - BACKGROUND: The use of a topical anesthetic cream containing prilocaine and
      lidocaine (EMLA) has been considered to reduce the pain of diagnostic allergy
      skin testing, but the effects of the cream on interpretation of skin tests is
      unclear. OBJECTIVE: To determine the effects of the cream for pain reduction
      using prick and ID skin tests and for possible alteration of wheal and flare
      responses to allergen, saline, and histamine. METHODS: In a randomized, double
      masked, placebo-controlled design, 20 adult volunteers with a history of positive
      allergen tests had EMLA and placebo cream placed according to the manufacturer's
      recommendations on the volar aspect of the arms. Paired skin tests were placed
      and subjects rated the tests on a pain scale from 0 to 5 and average wheal and
      flare diameters were determined. RESULTS: Mean pain scores (+/-SEM) were
      significantly reduced from 2.5 +/- 0.7 to 1.1 +/- 0.6 for prick tests (n = 20, P
      < .001) and from 3.2 +/- 0.9 to 1.13 +/- 0.9 for intradermal (ID) tests (n = 58,
      P < .001). The wheal sizes for allergen prick tests, allergen ID tests, and
      histamine ID tests were identical in comparing placebo to EMLA-treated skin.
      Flare responses were reduced on the actively treated skin, on average, as
      follows: allergen skin tests- 52% (P < .001), and histamine- 40% (P < .001). In
      nine tests there was complete suppression of the flare response, all on the EMLA
      treated skin. CONCLUSIONS: EMLA significantly reduced the pain associated with
      diagnostic allergy skin testing and with no effect on the size of the wheal
      response. It reduces the flare response, in some cases inhibiting it completely,
      which must be taken into consideration in interpreting results.

PMID- 9012625
TI  - Treatment of severe respiratory failure during status asthmaticus in children and
      adolescents using high flow oxygen and sodium bicarbonate.
AB  - OBJECTIVE: Status asthmaticus with respiratory failure is a potentially fatal
      complication of bronchial asthma. To prevent a fatality in status asthmaticus
      with respiratory failure, treatment with intravenous isoproterenol or mechanical
      ventilation has been advocated. These interventions also have serious potential
      complications, however, and while continuous inhalation of beta agonists has
      shown promise, the optimal therapy of severe status asthmaticus remains unclear.
      This paper describes our experience with a treatment protocol used in status
      asthmaticus with respiratory failure that seeks to avoid intravenous
      isoproterenol or assisted ventilation. STUDY DESIGN: Case series of pediatric
      intensive care patients with severe respiratory failure due to status
      asthmaticus. Six children and adolescents experienced a total of nine episodes of
      severe respiratory failure due to status asthmaticus. RESULTS: In seven of the
      nine episodes the patients were managed without either intravenous isoproterenol
      or mechanical ventilation. Hypercarbia persisted for an average of 25 hours
      (range 17 to 40 hours) in these seven episodes. All subjects recovered without
      notable sequelae. In two episodes, clinical and blood gas deterioration led to
      mechanical ventilation. Ventilation was required for 112 and 42 hours,
      respectively, in these episodes and the patients developed either pneumothorax or
      pneumomediastinum during ventilation. CONCLUSION: Using a protocol initiated in
      1978 for correction of hypoxia and acidemia, many patients with severe
      respiratory failure from status asthmaticus can be treated without isoproterenol
      or mechanical ventilation. Since those treatments have significant risks,
      consideration should be given to this intervention before resorting to them.

PMID- 9012626
TI  - Floctafenine: a valid alternative in patients with adverse reactions to
      nonsteroidal anti-inflammatory drugs.
AB  - BACKGROUND: Choosing an alternative anti-inflammatory agent for a patient who has
      suffered adverse reactions to nonsteroidal anti-inflammatory drugs is a common
      problem in clinical practice, and it is complicated by the possibility of non
      immunologic cross reactivity among the various members of this drug class.
      OBJECTIVE: We performed a retrospective study based on oral challenge results in
      150 patients with histories of adverse reactions to one or more nonsteroidal anti
      inflammatory drugs. The alternative drugs tested included floctafenine, an
      analgesic of the fenamic acid group, nimesulide, or paracetamol (acetaminophen).
      PATIENTS AND METHODS: One hundred fifty patients with histories of adverse
      reactions to nonsteroidal anti-inflammatory drugs received oral challenges with
      floctafenine; 101 were also challenged with nimesulide and paracetamol. The oral
      challenges were administered under single-blinded conditions. One-fourth of the
      therapeutic dose (floctafenine, 200 mg; nimesulide, 100 mg; and paracetamol, 500
      mg) was administered initially; the remaining 3/4 was given one hour later if no
      symptoms had developed with the initial administration. In patients with
      histories of rhinitis and/or bronchial asthma unrelated to drug use and those
      whose adverse reactions had included bronchospastic or rhinitic symptoms, the
      FEV1 was measured. The response to the challenge was considered positive if any
      of the following symptoms developed: erythema, pruritus accompanied by erythema,
      urticaria/ angioedema, rhinorrhea, nasal obstruction, sneezing, dyspnea or cough
      associated with a decrease of at least 20% in the FEV1, hypotension. RESULTS:
      Floctafenine challenges were positive in 13/150 patients (8.7%). Nimesulide and
      paracetamol provoked reactions in 9/101 patients (8.9%). All positive reactions
      occurred within 24 hours of the challenge. None of the patients reacted to more
      than one of the drugs tested. CONCLUSIONS: Our findings confirm those of other
      investigators regarding the use of nimesulide and paracetamol in patients who do
      not tolerate aspirin or other nonsteroidal anti-inflammatory drugs, although the
      percentage of reactions to nimesulide observed in the present study is somewhat
      higher than that reported by some other groups. The study also indicates that
      floctafenine, a relatively weak cyclooxygenase inhibitor, can be a valid
      alternative for many patients who react adversely to other nonsteroidal anti
      inflammatory drugs.

PMID- 9012628
TI  - Cost and safety of rush immunotherapy.

PMID- 9012627
TI  - Morrow Brown Allergy Diagnostic Needle.

PMID- 9012629
TI  - Angioedema associated with angiotensin-converting enzyme inhibitors.

PMID- 9012630
TI  - Human brain pericytes differentially regulate expression of procoagulant enzyme
      complexes comprising the extrinsic pathway of blood coagulation.
AB  - After vascular injury, pericytes may function in blood coagulation events that
      lead to thrombin formation due to their subendothelial location in the
      microvasculature. Pericytes from human cerebral cortex microvessels were isolated
      and characterized, and their ability to express and regulate procoagulant enzyme
      complexes was determined. Tissue factor was detected on the cell surface of
      cultured human brain pericytes by immunocytochemistry and was shown to form a
      functional complex with factor (F) VIIa to effect both FIX and FX activation.
      Treatment of pericytes with the calcium ionophore A23187 increased the observed
      tissue factor activity twofold to fivefold, which was shown to be due to an
      enhancement of cofactor activity and not the release of endogenous antigen
      stores. Pericytes also provided the appropriate membrane surface required for the
      assembly of a functional prothrombinase complex, so that in the presence of FVa
      and FXa, they effected thrombin formation 50 to 100 times faster than any other
      cell examined to date. In marked contrast to observations in other cell systems,
      pericyte expression of prothrombinase activity remained unaltered after treatment
      with A23187. As has been shown for platelets, the membrane receptor on pericytes
      for FXa assembly into the prothrombinase complex appears to at least partially
      consist of the FXa receptor effector cell protease receptor-1. These combined
      data indicate that pericytes can activate and propagate the coagulant response
      through the extrinsic pathway and that the activities of the required enzyme
      complexes can be differentially regulated in response to agonist stimulation.
      These observations support the concept that pericytes may play an important role
      in regulating coagulation events after cerebrovascular injury.

PMID- 9012631
TI  - Influence of hypercholesterolemia and adventitial inflammation on the development
      of aortic aneurysm in rabbits.
AB  - Abdominal aortic aneurysms are characterized by intimal atherosclerosis,
      disruption and attenuation of the elastic media, and a variable adventitial
      inflammatory infiltrate. We have developed an animal model of this disorder to
      evaluate the contribution of hypercholesterolemia, medial injury, and adventitial
      inflammation to aneurysmal dilatation. To accomplish this, we used periaortic
      application of calcium chloride, which induced both medial injury with
      calcification and endothelial injury. Ultrasonography was used to demonstrate the
      dilatation and thickening of the aortic wall. Over the first 3 weeks after
      periaortic application of 0.25 mol/L CaCl2, the external aortic diameter
      increased from 3.5 +/- 0.5 to 4.2 +/- 0.8 mm, but the ID remained unchanged. This
      apparent wall thickening was accompanied by vascular remodeling, and biochemical
      changes included approximately 50% reduction in tissue hydroxyproline
      concentration and increased activity of gelatinases (matrix metalloproteinase
      [MMP]-2 and MMP-9). Independently, cholesterol feeding to induce
      hypercholesterolemia or the concomitant periaortic application of thioglycollate
      had little effect on the histological, biochemical, or diameter changes.
      Together, hypercholesterolemia and thioglycollate were associated with rapid
      aortic dilatation in CaCl2, treated animals but not controls: after 3 weeks, the
      ID and OD had doubled, the OD increasing from 3.5 +/- 0.4 to 7.1 +/- 0.4 mm, P =
      .005. The remarkable feature that accompanied this dilatation was the
      infiltration of cells, mostly foamy macrophages, into the adventitia, with a
      further reduction in hydroxyproline concentration. Adventitial inflammation may
      provide the critical stimulus to dilatation of an aorta with preexisting intimal
      and medial injury.

PMID- 9012632
TI  - Effects of CSF-1 on cholesterol accumulation and efflux by macrophages.
AB  - To assess whether human monocyte-specific colony-stimulating factor (CSF-1) might
      influence atherogenesis, CSF-1-induced macrophage responses that might contribute
      to enhanced clearance of low-density lipoprotein (LDL) or modified LDL were
      investigated. Careful account was made of cell preservation and increases in cell
      volume and protein (representing increased cell surface area, and thus
      endocytically active membrane) during culture with CSF-1. This permitted
      distinction between selective and nonspecific effects of CSF-1, the latter
      paralleling increases in cellular mass and volume. CSF-1 enhanced mouse
      peritoneal macrophage survival in vitro during exposure to lipoprotein-deficient
      serum with or without native LDL or acetylated LDL (Ac-LDL), as judged by
      maintenance of cellular DNA and cell numbers. In the presence of copper-oxidized
      LDL (Ox-LDL), such effects were very slight. In all conditions, CSF-1 increased
      cellular protein content. CSF-1 increased the uptake of both Ac-LDL and Ox-LDL
      calculated per culture, but this was entirely explicable by the increased cell
      protein, indicating that there was no selective enhancement of scavenger receptor
      or other routes for uptake of the modified LDLs. Similarly, CSF-1 also increased
      the accumulation of cholesterol and its esters nonspecifically. CSF-1 did have a
      marked and specific effect on the composition of cholesterol esters, decreasing
      the proportion of polyunsaturated esters relative to monounsaturated and
      saturated esters. Finally, cholesterol efflux induced by apolipoprotein A1 from
      Ac-LDL-loaded macrophages was not influenced by CSF-1. Thus, the enhanced
      macrophage catabolism of modified LDLs by CSF-1 is part of a nonspecific action
      on the cells but could contribute to a reduction in circulating cholesterol,
      observed in some situations of CSF-1 presentation in humans.

PMID- 9012633
TI  - Studies on the mechanism of fibrate-inhibited expression of plasminogen activator
      inhibitor-1 in cultured hepatocytes from cynomolgus monkey.
AB  - Fibrates are widely used drugs in hyperlipidemic disorders. In addition to
      lowering serum triglyceride levels, fibrates have also been shown to reduce
      elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels in vivo. We
      demonstrate that fibrates suppress PAI-1 synthesis in cultured cynomolgus monkey
      hepatocytes in a concentration-dependent way (0.1 to 1.0 mmol/L) and independent
      of their lipid-lowering effect. Different fibrates showed different potency in
      suppressing PAI-1 production: gemfibrozil and clofibric acid, at a concentration
      of 1 mmol/L, reduced PAI-1 synthesis over 24 hours to 52 +/- 20% and 60 +/- 5%,
      while clofibrate and bezafibrate lowered PAI-1 synthesis to only 86 +/- 17% and
      84 +/- 15% of control values, respectively. These changes in PAI-1 production by
      fibrates correlated with changes in PAI-1 mRNA levels and were also visible at
      the level of gene transcription. Fibrates did not lower basal PAI-1 synthesis but
      attenuated an acceleration of PAI-1 production during culture. The suppressing
      effect of fibrates on PAI-1 synthesis could not be mimicked with activators or
      inhibitors of protein kinase C (PKC). Furthermore, fibrates did not inhibit the
      increase in PAI-1 synthesis induced by epidermal growth factor or transforming
      growth factor-beta. These results make mechanisms involving PKC modulation or
      growth factor receptor inactivation as a mode of action of fibrates unlikely. The
      suppressing effect of fibrates on PAI-1 synthesis could involve the nuclear
      receptor peroxisome proliferator-activated receptor (PPAR) and its heterodimeric
      partner, the retinoid X receptor (RXR). The alpha forms of PPAR and RXR were both
      found to be expressed in cynomolgus monkey hepatocytes. the ligand for RXR alpha,
      9-cis retinoic acid, suppressed PAI-1 synthesis to the same extent as
      gemfibrozil, while a combination of gemfibrozil and 9-cis retinoic acid had no
      more effect on PAI-1 synthesis than any of these compounds alone at optimal
      concentrations. In conclusion, fibrates downregulate an induced PAI-1 production
      in cynomolgus monkey hepatocytes independent of a decrease in triglyceride
      levels. A possible involvement of PPAR alpha/RXR alpha in this down-regulation is
      discussed.

PMID- 9012634
TI  - Plasminogen activator inhibitor-1 promoter 4G/5G genotype and plasma levels in
      relation to a history of myocardial infarction in patients characterized by
      coronary angiography.
AB  - To investigate the relationship between an insertion/deletion (4G/5G)
      polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI
      1) gene and the phenotypes of PAI-1 levels, coronary atheroma, and a past history
      of coronary thrombosis, we studied 453 patients (320 men and 133 women)
      characterized by coronary angiography. Patients were classified as having normal
      vessels (n = 125) or single-vessel (n = 92) or multivessel (n = 232) coronary
      disease on the basis of > or = 50% stenosis. PAI-1 antigen levels were highest in
      patients with the 4G/4G genotype (22.5 ng/mL), with a stepwise decrease in levels
      as the number of 4G alleles decreased (21.5 ng/mL for 4G/5G and 15.8 ng/mL for
      5G/5G, P = .02) after adjusting for age, sex, triglyceride levels, and body mass
      index (BMI). The association between triglyceride level and PAI-1 was genotype
      specific, with a steeper slope in subjects with the 4G/4G genotype (P = .004). A
      gene-environment interaction between BMI, PAI-1, and genotype was observed, with
      a steeper association in patients with the 5G/5G genotype (P = .02). The 4G/4G
      genotype was significantly associated with a history of myocardial infarction (P
      < .03; odds ratio, 2.0; 95% CI, 1.1 to 3.7). This relationship was stronger in
      subjects with diseased vessels (P = .006). There was no relationship between
      either PAI-1 genotype or levels and the presence of atheroma. Our data suggest
      that PAI-1 promoter polymorphism influences the development of myocardial
      infarction through its effect on thrombus formation in patients with preexisting
      coronary atheroma.

PMID- 9012635
TI  - Polymorphisms of the genes encoding apoproteins A-I, B, C-III, and E and LDL
      receptor, and cholesterol and LDL metabolism during increased cholesterol intake.
      Common alleles of the apoprotein E gene show the greatest regulatory impact.
AB  - Genetic and dietary factors regulate serum cholesterol level, but detailed
      investigations into their interactions have not been established. We assessed the
      effects of apoprotein (apo) E phenotype and polymorphic alleles of the apo A-I,
      apo B, apo C-III, and LDL receptor genes, separately and together, on regulation
      of serum LDL cholesterol level. The study group consisted of 29 middle-aged men,
      and cholesterol absorption, bile acid, and cholesterol synthesis and LDL apo B
      kinetics were studied in these men during low- and high-cholesterol diets. The
      six apo B alleles were identified on the basis of Xba I, EcoRI, and Msp I
      restriction fragment length polymorphism (RFLP), the apo A-I alleles with the Msp
      I RFLP, and the apo C-III and LDL receptor alleles corresponded to the Sst I and
      PvuII RPLPs of these genes, respectively. During low cholesterol intake, LDL
      cholesterol levels were similar in all of the genetic groups except for men with
      apo E2 phenotype. They had significantly (P < .05) lower levels of LDL apo B and
      cholesterol than men without the epsilon 2 allele. The low values were caused by
      a significantly higher removal of LDL apo B (apo E2, 0.453 +/- 0.03 versus apo
      E3, 0.312 +/- 0.01 pools per day, P < .05). High cholesterol intake increased LDL
      cholesterol levels in all genetic categories except in the apo E2 phenotype
      irrespective of the combinations with other polymorphisms. Carriers of the apo B
      R+ allele (EcoRI site present) presented with the most prominent LDL cholesterol
      rise (from 2.71 +/- 0.14 to 3.37 +/- 0.29 mmol/L). In multiple stepwise
      regression analysis, apo B EcoRI RFLP and apo E phenotypes were the only
      variables that explained the variability of high cholesterol intake-induced
      change in LDL cholesterol levels. In summary, in any genetic combination,
      individuals with the epsilon 2 allele had the lowest LDL cholesterol values and
      were nonresponders to dietary cholesterol, whereas subjects with the apo B R+
      allele had marked LDL elevations, especially in combination with the epsilon 4.

PMID- 9012636
TI  - Fibrinogen and its relations to subclinical extracoronary and coronary
      atherosclerosis in hypercholesterolemic men.
AB  - The association between plasma fibrinogen and the presence of carotid, femoral,
      and aortic plaque (high-resolution B-mode ultrasonography) and coronary calcium
      deposit (ultrafast computed tomography scanner) was determined in 693
      hypercholesterolemic, never-treated men free of previous or current clinical
      symptoms of cardiovascular disease. The number of subjects with extracoronary
      disease sites and coronary calcification deposits was significantly higher in the
      upper than in the lower tertile of fibrinogen. Plasma fibrinogen increased
      according to the number of diseased sites. The odds ratio of the upper to lower
      fibrinogen tertile for the presence of arterial lesions was 2.6 (1.7 to 4) for
      carotid, 2.2 (1.5 to 3.2) for aorta, 2.2 (1.5 to 3.1) for femoral, 1.8 (1.3 to
      2.6) for coronary, and 3.6 (2.3 to 6.1) for one of four diseased sites.
      Adjustment for age, total cholesterol, HDL cholesterol, triglycerides, current
      smoking, and systolic pressure slightly reduced the association between
      fibrinogen and atherosclerosis. A synergistic effect between fibrinogen and total
      cholesterol/ HDL cholesterol (TC/HDL) ratio seemed to be operating on
      atherosclerosis, because nearly all of the individuals (98%) had a diseased site
      when fibrinogen and TC/HDL tertiles were the highest. This result suggests that
      fibrinogen is involved in the subclinical phase of extracoronary and coronary
      atherosclerosis and may potentiate the atherogenic effect of hyperlipidemia.

PMID- 9012637
TI  - Factor VII, cholesterol, and triglycerides. The CARDIA Study. Coronary Artery
      Risk Development in Young Adults Study.
AB  - Cross-sectional studies have shown that factor VII coagulant activity (VIIc) is
      positively associated with plasma total cholesterol (TC), LDL cholesterol, and
      triglycerides (TG) as well as body mass index (BMI) and diastolic blood pressure.
      To determine whether changes in VIIc parallel changes in coronary risk factors
      over a period of 2 years, we examined data from 1514 participants in the Coronary
      Artery Risk Development in Young Adults Study (CARDIA), an ongoing investigation
      of lifestyles and evolution of cardiovascular risk factors. Subjects were 23 to
      35 years old at the year 5 examination. Cross-sectional analyses at these
      examinations showed that VIIc was positively correlated (P < .001) with TC and TG
      in all race/sex groups except for TC in black women at the year 5 examination.
      Changes in VIIc over the 2-year period were correlated positively with changes in
      TC in all except black men and TG in all groups; the association of VIIc change
      with change in TC and TG was reduced only slightly with adjustment for age and
      BMI at year 5 and 2-year change in BMI. To determine whether the higher levels of
      VIIc in subjects with higher lipid values were due to activation of the factor or
      to an increase in the concentration of the factor VII clotting protein, we
      measured factor VII antigen (VIIag) in a randomly selected subsample of 223
      subjects at the year 7 examination. In all sex/race groups, VIIag correlated with
      VIIc (r = .69 to 0.81). After adjustment for sex and race, the partial
      correlation coefficient between TG and VIIc was .28 (P = .0001); between TG and
      VIIag, .35 (P = .0001); between TC and VIIc, .39 (P = .0001); and between TC and
      VIIag, 0.43 (P = .0001). No associations were observed between lipid levels and
      the ratio of VIIc to VIIag. We conclude that the raised VIIc with higher lipid
      levels occurs in blacks as well as whites, in men and women, persists over time,
      and represents a true increase in the plasma concentration of this clotting
      factor.

PMID- 9012638
TI  - Determinants of plasma HDL-cholesterol in hypertriglyceridemic patients. Role of
      cholesterol-ester transfer protein and lecithin cholesteryl acyl transferase.
AB  - Hypertriglyceridemic patients commonly have low levels of HDL cholesterol.
      Elevated triglycerides per se may be one cause of low HDL levels, but other
      factors also may be involved. The current study was designed to define the role
      of cholesterol-ester transfer protein (CETP) in causation of a low HDL
      cholesterol in hypertriglyceridemic patients; in addition other factors-lecithin
      cholesterol acyl transferase (LCAT), hepatic triglyceride lipase (HTGL), and
      lipoprotein lipase (LPL)-were examined. Plasma activities of CETP and LCAT were
      measured in 137 male patients with moderate hypertriglyceridemia (plasma
      triglycerides [TGs] 200 to 500 mg/dL and LDL cholesterol < 160 mg/dL). Results
      were compared with those from 50 normolipidemic men of similar age and body
      habitus. In addition, lipase activities in postheparin plasma were measured in
      118 of the subjects with hypertriglyceridemia. The activities of CETP and LCAT
      were 17% (P < .01) and 7% (P < .05), respectively, higher in the
      hypertriglyceridemic group than in control subjects. By stepwise regression
      analysis CETP appeared to contribute 15.2% and LCAT 9.8% to variation in HDL
      cholesterol levels. Activities of LPL and HTGL together contributed an additional
      14.1% to HDL-cholesterol variation. In contrast, levels of plasma TG accounted
      for only 5.4% of the variation. There were no differences in relative
      contributions of these parameters in patients with and those without coronary
      heart disease. This study indicates that several factors contribute to the
      variation in HDL-cholesterol levels in hypertriglyceridemic patients, and five
      factors-CETP, LCAT, HTGL, LPL, and triglyceride levels-account for almost half of
      this variation.

PMID- 9012639
TI  - Differences in insulin suppression of free fatty acid levels by gender and
      glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B
      concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators.
AB  - Most discussions of relations of insulin resistance to coronary heart disease
      risk factors have focused on insulin-stimulated glucose uptake, but insulin
      suppression of plasma free fatty acid (FFA) levels is also important in lipid and
      lipoprotein metabolism. To identify groups with impaired insulin suppression of
      FFAs, we studied a multiethnic cohort of 1521 women and men at four US centers
      that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with
      normal glucose tolerance, 352 with impaired glucose tolerance, and 487 with non
      insulin-dependent diabetes. The FFA level 2 hours after a 75-gm oral glucose load
      adjusted for fasting FFAs was used as the measure of insulin suppression. After
      adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour
      insulin levels, 2-hour FFA levels were significantly higher in men than women and
      in persons with impaired glucose tolerance and non-insulin-dependent diabetes
      mellitus versus normal glucose tolerance. The gender difference was largely
      accounted for by differences in central obesity as measured by waist-hip ratio;
      the difference by glucose tolerance status was not affected by central obesity,
      suggesting a different mechanism. In multivariate regression analyses, 2-hour FFA
      levels were strongly related to fasting triglyceride and apoB levels,
      respectively, after adjustment for age, fasting and 2-hour insulin
      concentrations, and fasting FFA concentrations. In summary, elevated plasma apoB
      and triglyceride concentrations associated with male gender and with glucose
      intolerance are partly accounted for by differences in the ability of insulin to
      suppress FFA concentrations.

PMID- 9012641
TI  - Apolipoprotein A-IFin. Dominantly inherited hypoalphalipoproteinemia due to a
      single base substitution in the apolipoprotein A-I gene.
AB  - We have identified a large kindred with severe serum HDL cholesterol deficiency.
      The proband, a 65-year-old woman, had greatly diminished concentrations of serum
      HDL cholesterol (0.19 mmol/L) and apolipoprotein (apo) A-I (21.9 mg/dL). HDL
      cholesterol and apo A-I levels were similarly reduced in all affected family
      members, while apo A-II levels were about half of those in the nonaffected family
      members. Pedigree analysis suggested a dominant inheritance pattern of the
      phenotype. Sequence analysis of the exons and exon-intron boundaries of the apo A
      I gene revealed heterozygosity for a single T-to-G point mutation substituting
      arginine for leucine at residue 159 of the mature apo A-I protein (apo A-IFin).
      The T-to-G substitution destroys an Fsp I cleavage site, permitting direct
      polymerase chain reaction/restriction enzyme analysis of the mutation. All the
      affected family members were shown to be heterozygous for the apo A-IFin
      mutation. Isoelectric focusing revealed the presence of the mutant apo A-IFin
      protein in both serum and HDL of the affected subjects. Functional consequences
      of the mutation were examined by expressing the mutated and wild-type apo A-I
      cDNAs in COS-7 cells. The mutant apo A-I mRNA had a size similar to that of the
      normal mRNA, and both mutant and wild-type apo A-I proteins were secreted into
      the cell media. In vivo kinetic studies of apo A-I revealed increased catabolism
      in affected subjects. In conclusion, we describe a novel point mutation of the
      apo A-I gene, apo A-IFin, causing a dominantly negative phenotype as regards
      serum HDL levels, possibly due to increased catabolism of apo A-I.

PMID- 9012640
TI  - A familial combined hyperlipidemic kindred with impaired apolipoprotein B
      catabolism. Kinetics of apolipoprotein B during placebo and pravastatin therapy.
AB  - Familial combined hyperlipidemia (FCHL) is a heterogeneous disorder characterized
      by multiple lipoprotein phenotypes, a high risk for coronary heart disease, and
      predominance among the LDL fraction of smaller and denser particles. We report on
      an FCHL kindred (the M-kindred) in which decreased VLDL- and LDL-apoB elimination
      rates rather than enhanced production rates were the main kinetic abnormalities.
      Lipoprotein levels and metabolic parameters of all apoB-containing lipoproteins
      (including light and dense LDLs) were determined during placebo and pravastatin
      treatment periods. ApoB metabolism was studied by endogenous labeling with stable
      isotopes and a multicompartmental model. Five members of the M-kindred
      participated. The study was doubly blinded, randomized, and placebo controlled.
      Treatment periods of 6 weeks were separated by 2-week washout periods. All
      subjects had high apoB levels, 2 had a mixed lipemia, 1 had hypercholesterolemia,
      and 2 had hypertriglyceridemia. Familial dysbetalipoproteinemia,
      hypercholesterolemia, and defective apoB-100 were excluded by genetic, testing.
      Kinetic parameters were remarkably similar in the five study subjects during the
      placebo period, despite their diverse plasma lipid profiles. Compared with nine
      normolipidemic control subjects, low VLDL-apoB fractional catabolic rates (FCRs)
      (3.6 +/- .1 versus 9.3 +/- 2.9 pools per day) and low LDL-apoB FCRs (0.19 +/-
      0.05 versus 0.41 +/- 0.13 pool per day) were observed in every case. The majority
      of the LDL particles were identified in the denser fraction (d = 1.036 to 1.063
      g/mL). A clear precursor-product relationship was observed from VLDL to IDL to
      light LDL to dense LDL, ie, there was no "metabolic channeling." Light LDL had
      significantly higher FCR than dense LDL (0.82 +/- 0.21 versus 0.22 +/- 0.08 pool
      per day). VLDL-apoB production rates were normal (19.7 +/- 6.0 versus 21.6 +/-
      6.1 mg/kg per day for control subjects). In contrast, in two subjects drawn from
      two other FCHL kindreds (the C- and K-kindreds), VLDL-apoB production rates were
      increased (35.6 and 32.1 mg/kg per day, respectively). In these two, more
      "typical" FCHL subjects, FCRs of LDL-apoB were near normal (0.351 and 0.311 pool
      per day, respectively). Pravastatin (20 mg/d) resulted in significantly lower
      plasma cholesterol (265 +/- 30 to 218 +/- 16 mg/dL, P < .01), LDL cholesterol
      (186 +/- 31 to 145 +/- 15 mg/dL, P < .03), and apoB levels (168 +/- 14 to 125 +/-
      16 mg/dL, P < .01) in the five FCHL subjects of the M-kindred. No changes were
      observed in plasma HDL cholesterol, apoA-I, or lipoprotein(a). Pravastatin
      significantly increased the LDL-apoB FCR (from 0.19 +/- 0.05 to 0.34 +/- 0.04
      pool per day). The FCRs of both LDL subclasses increased with treatment. No
      pravastatin-induced changes were seen in apoB production rates.

PMID- 9012642
TI  - Polymorphism of the apolipoprotein E gene and early carotid atherosclerosis
      defined by ultrasonography in asymptomatic adults.
AB  - Clinical and autoptical studies have suggested a predisposing role of the allele
      E4 of apolipoprotein E (apoE) in the development of atherosclerosis and
      cardiovascular disease. To investigate the possible contribution of apoE allele
      polymorphism to the carotid intima-media thickness (IMT) as assessed by
      ultrasound, we studied 260 asymptomatic nondiabetic subjects (121 men, 139 women;
      mean +/- SD age, 53 +/- 7 years), randomly selected from the population register
      of the inhabitants of Trieste, Italy. B-mode ultrasound was used to quantify the
      maximum IMT at 12 sites on the near and far wall of the common, bifurcation, and
      internal carotid arteries. ApoE genotypes were determined from amplified apoE
      sequences by restriction isotyping. The frequencies of E2, E3, and E4 alleles
      were 0.073, 0.827, and 0.100, respectively. As expected, subjects with E4 allele
      had the highest levels of total serum cholesterol and LDL cholesterol, subjects
      with E2 allele had the lowest levels, and those with E3 genotype had intermediate
      levels. The echographic measurements of carotid IMT showed increasing values from
      E2 to E4 carriers. After adjustment for total and LDL cholesterol serum levels,
      triglycerides, ratio of LDL to HDL cholesterol, age, sex, and body mass index,
      ANCOVA showed that the common carotid IMT was significantly greater (P = .029) in
      subjects with E4 allele compared with E3 carriers. Our data confirm the influence
      of apoE4 on cholesterol levels and clearly show that apoE genotype affects
      carotid atherosclerosis in its early stages in middle-aged asymptomatic subjects.

PMID- 9012644
TI  - Isolated low HDL cholesterol as a risk factor for coronary heart disease
      mortality. A 21-year follow-up of 8000 men.
AB  - For the purpose of screening individuals at high risk for coronary heart disease
      (CHD), serum total cholesterol (TC) of 5.2 mmol/L, has been set as a value
      dividing "desirable" from intermediate high or elevated levels, and HDL
      cholesterol (HDL-C) < 0.9 mmol/L has been labeled as abnormally low, implying
      high CHD risk. It has been conjectured that low HDL-C poses no risk in the
      absence of elevated LDL cholesterol or TC. To assess the risk of CHD-free men
      with "isolated low HDL-C," ie, abnormally low HDL-C with desirable TC, we
      examined the CHD and all-cause mortality of some 8000 Israeli men aged 42 years
      and older during 1965 through 1986. Men with isolated low HDL-C represented one
      sixth of the cohort. CHD mortality among these men was 36% higher (age adjusted)
      than in counterparts with desirable TC, of which > 0.9 mmol/L was contained in
      the high-density fraction. In men with TC > 5.2 mmol/L, abnormally low HDL-C was
      associated with a virtually identical CHD mortality risk ratio, 38%. These
      findings persisted after adjustment for multiple CHD risk factors. The excess CHD
      risk associated with isolated low HDL-C appeared particularly increased in men
      with diabetes mellitus, whose death rate was 65% higher than in diabetics with
      HDL-C > 0.9 mmol/L. A second subgroup result was consistent with equal CHD
      mortality risk among men in the "desirable" TC range, with or without low HDL-C,
      if systolic blood pressure was > 160 mm Hg. These are post hoc findings, and
      hypotheses arising from these observations would require independent examination.
      Total mortality was not increased in men with isolated low HDL-C compared with
      men who had HDL-C < 0.9 mmol/L and TC > 5.2 mmol/L at baseline. These results
      indicate that an increased risk of CHD death is associated with abnormally low
      HDL-C for cholesterol ranges both below and above 5.2 mmol/L. For the individual,
      therefore, the risk is multiplied by the same amount regardless of TC. Quitting
      smoking, increasing physical activity, and decreasing body weight would all
      contribute to raise HDL-C in individuals of most or all age groups. When examined
      from a community perspective, the results are consistent with a relatively low
      population-attributable fraction among CHD-free men. This would tend to support
      the recommended practice of considering a TC level of 5.2 mmol/L (200 mg/dL) as a
      threshold for further evaluation in screened individuals without manifest CHD.

PMID- 9012643
TI  - Effects of serum lipoproteins and smoking on atherosclerosis in young men and
      women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis
      in Youth.
AB  - Atherosclerosis begins in childhood and progresses from fatty streaks to raised
      lesions in adolescence and young adulthood. A cooperative multicenter study
      (Pathobiological Determinants of Atherosclerosis in Youth [PDAY]) examined the
      relation of risk factors for adult coronary heart disease to atherosclerosis in
      1079 men and 364 women 15 through 34 years of age, both black and white, who died
      of external causes and were autopsied in forensic laboratories. We quantitated
      atherosclerosis of the aorta and right coronary artery as the extent of intimal
      surface involved by fatty streaks and raised lesions and analyzed postmorterm
      serum for lipoprotein cholesterol and thiocyanate (as an indicator of smoking).
      The extent of intimal surface involved with both fatty streaks and raised lesions
      increased with age in all arterial segments of all sex and race groups. Women had
      a greater extent of fatty streaks in the abdominal aorta than men, but women and
      men had about an equal extent of raised lesions. Women and men had a comparable
      extent of fatty streaks in the right coronary artery, but women had about half
      the extent of raised lesions. Blacks had a greater extent of fatty streaks than
      whites, but blacks and whites had a similar extent of raised lesions. VLDL plus
      LDL cholesterol concentration was associated positively and HDL cholesterol was
      associated negatively with the extent of fatty streaks and raised lesions in the
      aorta and right coronary artery. Smoking was associated with more extensive fatty
      streaks and raised lesions in the abdominal aorta. All three risk factors
      affected atherosclerosis to about the same degree in both sexes and both races.
      Primary prevention of atherosclerosis by controlling these adult coronary heart
      disease risk factors is applicable to young men and women and to young blacks and
      whites.

PMID- 9012645
TI  - Plasma protein C inhibitor is elevated in survivors of myocardial infarction.
AB  - Many studies have shown alterations of the hemostatic and fibrinolytic systems in
      patients with atherosclerotic disease, principally in levels of plasminogen
      activator inhibitor-1. However, in a large prospective study only fibrinogen, von
      Willebrand factor antigen, and tissue plasminogen activator antigen were found to
      be independent risk markers for acute coronary events. The present study
      evaluated the fibrinolytic system in coronary artery disease, paying particular
      attention to another inhibitor of fibrinolysis, plasminogen activator inhibitor
      3, also called protein C inhibitor (PCI). One hundred fifteen nonanticoagulated
      male survivors of myocardial infarction were investigated for a range of
      hemostatic and fibrinolytic parameters that were compared with values in 87 age
      matched healthy control male subjects. PCI active antigen was significantly (P <
      .03) elevated in the myocardial infarction group compared with the control group
      and was associated with the number of acute coronary events suffered (P = .005)
      but not with the severity of disease as determined by coronary angiography.
      Elevated PCI plasma levels can be considered as a risk marker for acute coronary
      events and might be of particular importance in the pathogenesis of this disease
      due to the interference of PCI in both the anticoagulant and fibrinolytic
      systems.

PMID- 9012646
TI  - "Tall oil"-derived phytosterols reduce atherosclerosis in ApoE-deficient mice.
AB  - We investigated the effects of a "tall oil"-derived phytosterol mixture (TODPM)
      on the formation of atherosclerotic lesions in apoE-deficient mice. TODPM was
      added at 2% (wt/wt) to the chow of nine mice; the control group had six animals.
      The diet of all animals contained 9% (wt/wt) fat and 0.15% (wt/wt) cholesterol.
      After 4 weeks, plasma total cholesterol levels were significantly reduced in the
      TODPM-treated mice (26.6 versus 42.0 mmol/L, P < .0001). The mean body weight of
      the TODPM-supplemented group was significantly higher at week 5 and throughout
      the study (29.4 versus 27.7 g, P < .05). The experiment was terminated at 18
      weeks. Histological examination showed mature atherosclerotic lesions composed of
      foam cells underlying the endothelium, a mosaic of extracellular
      glycosaminoglycans, numerous apparently proliferative smooth muscle cells, and
      foci of cholesterol clefts in the control animals. By contrast, the TODPM-treated
      mice showed only early lesions containing mainly superficial foam cells. As
      assessed by morphometry, the lesion area in the aortic sinuses of TODPM-treated
      animals was less than half that of control animals (P < .0001). This reduced
      lesion area was accompanied by a substantial reduction in all lesional
      components, reflecting a delay in progression of atheromatous changes. A strong
      positive correlation (r = .69, P < .01) was found between plasma total
      cholesterol levels and lesion area in the aortic sinuses. TODPM also prevented
      the occurrence of xanthomatosis. We conclude that supplementation of a
      cholesterol-enriched diet with TODPM significantly lowers plasma cholesterol and
      retards development of atherosclerosis in apoE-deficient mice, suggesting a
      therapeutic potential for the mixture of phytosterols studied.

PMID- 9012647
TI  - The redox status of coenzyme Q10 in total LDL as an indicator of in vivo
      oxidative modification. Studies on subjects with familial combined
      hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence
      of a multiple-type hyperlipidemia, associated with coronary risk. The latter may
      be related to increased levels of small, dense LDL particles that have been found
      to be more prone to oxidative modification. We isolated total LDL as fresh as
      possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile
      (group 1), 7 normolipidemic subjects with a dense LDL subfraction profile (group
      2), and 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile
      (group 3). In these nonobese and normotensive men, we studied the resistance of
      total LDL against Cu(2+)-oxidation in vitro. In addition, we analyzed the alpha
      tocopherol and the coenzyme Q10 contents of LDL and determined their relation to
      LDL oxidizability. LDL isolated from group 3 subjects was more susceptible to
      oxidative modification than LDL from group 1 subjects (lag time: 60.4 +/- 8.1
      versus 70.4 +/- 11.4 minutes; P < .05). For the combined groups, the ratio of
      ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal
      amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R2 =
      .73, P = .0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol
      10/ubiquinone-10) and the ratio of ubiquinol-10 to alpha-tocopherol in LDL were
      reduced compared with group 1 (P < .05). The K-value a measure of the LDL
      density, correlated with the the redox status (r = .37, P < .05). We conclude
      that in subjects with FCH total LDL is more prone to oxidation, due to the
      predominance of dense LDL particles. In addition, the decreased redox status of
      coenzyme Q10 in LDL from subjects with a dense LDL subfraction profile suggests
      that the LDL in the circulation has already undergone some oxidation.

PMID- 9012648
TI  - Circulating autoantibodies recognizing peroxidase-oxidized low density
      lipoprotein. Evidence for new antigenic epitopes formed in vivo independently
      from lipid peroxidation.
AB  - Oxidatively modified LDLs are antigenic and elicit the generation of
      autoantibodies often detected in plasma and within plaques of atherosclerotic
      patients. Although Cu(2+)-oxidized LDL and malondialdehyde (MDA)-modified LDL are
      usually used as antigens in immunoassays, other, still unrecognized epitopes may
      be formed in vivo during LDL oxidation and may induce antibody production.
      Antibodies recognizing LDL oxidatively modified by Cu2+, 2,2'-azobis-(2-amidino
      propane) hydrochloride (AAPH), and the combination of horseradish peroxidase and
      H2O2 (HRP) were detected in serum of a group of 90 unselected patients. HRP
      oxidized LDL was the antigen that revealed the highest IgG titers, although the
      extent of LDL oxidation (evaluated as conjugated diene formation, loss of
      tryptophan fluorescence, production of fluorescent aldehydic adducts, and change
      in electrophoretic mobility) was comparable to that obtained with Cu2+ and AAPH.
      There was a highly statistically significant correlation between the IgG titers
      detected using Cu(2+)- and AAPH-oxidized LDLs as antigens, but no correlation was
      found between the IgG titers revealed by HRP and Cu2+ or AAPH. In addition, the
      antibody titers against MDA-modified LDL exhibited a significant correlation with
      those against Cu(2+)- or AAPH-oxidized LDL but did not correlate with those
      against HRP-oxidized LDL. Finally, immunocompetition experiments revealed that
      IgG recognizing HRP-oxidized LDL did not cross-react with Cu(2+)-oxidized LDL and
      vice versa. The possibility that lipid peroxidation-independent modifications
      could play a role in HRP-induced formation of antigenic epitopes in LDL was
      supported by two lines of evidence. First, in probucol-enriched LDL, despite the
      complete inhibition of lipid peroxidation, HRP, but not Cu2+ and AAPH, was still
      able to generate epitopes that were recognized by the same sera reacting with HRP
      oxidized native (not probucol-enriched) LDL. In addition, the presence of
      autoantibodies against Cu(2+)- and AAPH-oxidized LDLs was negatively correlated
      with serum alpha-tocopherol concentration, whereas the titers against HRP
      oxidized LDL did not exhibit any statistically relevant correlation with alpha
      tocopherol levels. Together, these findings indicate that peroxidase(s)-dependent
      mechanisms can trigger peculiar lipid peroxidation-independent modifications of
      LDL in vivo.

PMID- 9012650
TI  - Possible functional interactions of apolipoprotein B-100 segments that associate
      with cell proteoglycans and the ApoB/E receptor.
AB  - The interaction of apoE lipoproteins with cells appears to be mediated by an
      association with basic sequences of proteoglycans and the apoB/E receptor. ApoB
      100 has basic sequences, homologous with those of apoE, that form part of the
      apoB/E receptor-binding domain. These sequences of apoB-100 also interact with
      proteoglycans. We investigated whether such segments, in analogy with apoE, could
      act cooperatively on LDL interactions with proteoglycans and the receptor. As a
      model we used the two most basic regions of apoB-100, 3147 through 3157 and 3359
      through 3367, connected by three glycines (3145-3157-GGG-3359-3367). Such
      segments may be proximal in LDL by the presence of a disulfide bridge between
      Cys(3167) and Cys(3297). The apoB heterodimer but not the separated monomers
      inhibited 125I-LDL degradation in fibroblasts and THP-1 cells by 50% at
      approximately 11 mumol/L. The heterodimer affinity with arterial proteoglycans
      was closer to that of LDL and higher than that of the individual peptides. The
      heterodimer appears to bind specifically to THP-1 cells, with a Kd of 6.2 x 10(
      8) mol/L and a Bmax of 1.3 x 10(6) molecules/cell. Monoclonal antibody C-7, which
      recognizes the apoB receptor, inhibited the binding to cells. Treatment of
      fibroblasts with chondroitinase ABC or chlorate decreased 125I-LDL degradation
      markedly. Hydrolysis of pericellular proteoglycans of fibroblasts by
      chondroitinases reduced mostly the low-affinity, high-capacity component of LDL
      binding. This compartment appears to hold 70% of the cell-associated LDL when
      internalization is inhibited at 4 degrees C. Therefore, cell-surface chondroitin
      sulfate/dermatan sulfate proteoglycans appear to modulate binding and receptor
      mediated internalization of LDL. This may be caused, at least in part, by the
      association of proteoglycans with the apoB-100 segments 3145 through 3157 and
      3359 through 3367.

PMID- 9012649
TI  - Oxidized LDL stimulates mitogen-activated protein kinases in smooth muscle cells
      and macrophages.
AB  - It has been proposed that oxidized LDL is more atherogenic than native LDL.
      However, the mechanisms by which native LDL and oxidized LDL alter function of
      cells in the vessel wall remain undefined. A signal transduction pathway that
      mediates many changes in cell function is the mitogen-activated protein (MAP)
      kinase cascade. We therefore examined the effect of native LDL and oxidized LDL
      on MAP kinase activity in cultured vascular smooth muscle cells (VSMC),
      endothelial cells, and macrophages by using an in-gel-kinase assay and anti
      phosphotyrosine MAP kinase antibodies. Native LDL and LDL oxidized by the
      addition of Cu2+ (Cu(2+)-oxidized LDL) stimulated MAP kinase in a time- and dose
      dependent manner in baboon and rat VSMC but not in bovine endothelial cells.
      Cu(2+)-oxidized LDL stimulated MAP kinase in human monocyte-derived macrophages,
      but the effect was much greater in cells cultured for 7 days compared with 1 day,
      suggesting dynamic regulation of the cellular response to oxidized LDL. In rat
      VSMC, the maximal MAP kinase response to Cu(2+)-oxidized LDL was significantly
      greater than the response to native LDL. Cu(2+)-oxidized LDL was more potent,
      with half-maximal activation at 15 micrograms/mL versus 30 micrograms/mL for
      native LDL. Stimulation of MAP kinase appeared to involve protein kinase C, since
      phorbol ester pretreatment for 24 hours blocked MAP kinase activation. Oxidation
      of LDL by other methods showed that activation of MAP kinase was not well
      correlated with lipid peroxides or aldehydes, suggesting that other components
      present in oxidized LDL were responsible. The active moiety appeared to be lipid
      based on extraction of oxidized LDL with organic solvents. These data indicate
      that LDL stimulates MAP kinase in VSMC, oxidation of LDL potentiates the effect,
      a lipid moiety is involved, and Cu(2+)-oxidized LDL activation of MAP kinase is
      cell-type specific. These findings suggest a role for MAP kinase in the pathways
      by which oxidized LDL contributes to altered cellular function associated with
      atherogenesis.

PMID- 9012651
TI  - Platelet integrin alpha IIb beta 3 (GPIIb-IIIa) is not implicated in the binding
      of LDL to intact resting platelets.
AB  - It has been suggested that the fibrinogen receptor (glycoprotein [GP] IIb-IIIa or
      platelet integrin alpha IIb beta 3) could be the binding site for low-density
      lipoprotein (LDL); however, recent data do not support this. Furthermore, GPIIb
      and not the GPIIb-IIIa complex is the main binding protein for lipoprotein(a)
      [Lp(a)]. In the present study, we have investigated the interaction between Lp(a)
      particles and platelet LDL binding sites and whether platelet integrin alpha IIb
      beta 3 is implicated. Displacement experiments showed that 125I-LDL binding to
      intact resting platelets was inhibited with the same apparent affinity by both
      unlabeled LDL and apolipoprotein(a)-free lipoprotein particles [Lp(a)-, an LDL
      like particle prepared from Lp(a)]. Hill coefficients for displacement curves
      suggested that a single set of binding sites was involved. In contrast, both
      native and oxidized Lp(a) particles were unable to inhibit platelet LDL binding.
      Furthermore, platelets bound 125I-Lp(a)- particles to a class of saturable
      binding sites numbering approximately 1958 +/- 235 binding sites per platelet
      with a dissociation constant (Kd) of 48.3 +/- 12 x 10(-9) mol/L. These values
      were similar to those obtained for LDL. In contrast to Lp(a), evidence indicates
      that platelet integrin alpha IIb beta 3 was not involved in the interaction of
      LDL and intact resting platelets. First, specific ligands for platelet integrin
      alpha IIb beta 3, such as fibrinogen, vitronectin, and fibronectin, were unable
      to inhibit the binding of LDL to intact resting platelets. Second, similar LDL
      binding characteristics (Kd and Bmax values) were found in platelets from control
      subjects and patients with type I and type II Glanzmann's thrombasthenia,
      characterized by total and partial lack of GPIIb-IIIa and fibrinogen,
      respectively. Third, polyclonal antibodies against the GPIIb-IIIa complex (edu-3
      and 5B12), human antiserums against platelet alloantigens (anti-Baka/B and anti
      PLA1/2), anti-integrin subunits (anti-alpha v and anti-beta 3), and a wide panel
      of monoclonal antibodies (mAbs) against well-known epitopes of GPIIb (M3, M4, M5,
      M6, and M95-2b) and GPIIIa (P23-7, P33, P37, P40, and P97) did not affect
      platelet LDL binding. Finally, in contrast to the proaggregatory effect of native
      and oxidized LDL, both native and oxidized Lp(a) particles caused a significant
      dose-dependent decrease of collagen-induced platelet aggregation. In conclusion,
      we demonstrate that neither the GPIIb-IIIa complex nor GPIIb and GPIIIa
      individually are membrane binding proteins for LDL on intact resting platelets.
      Lp(a) particles do not interact with platelet LDL binding sites, and their
      biological response is clearly different from that of LDL.

PMID- 9012652
TI  - Complement C5b-9 increases plasminogen binding and activation on human
      endothelial cells.
AB  - Deposition of the terminal complement proteins (C5b-9) on human endothelial cells
      can result in cell lysis or nonlytic alterations of cell function including
      procoagulant responses. Because regulation of fibrinolysis is a central
      endothelial function and because C9 contains a carboxyl-terminal lysine similar
      to other proteins that bind and facilitate activation of plasminogen (PG), the
      effects of complement injury on PG binding and activation on these cells were
      investigated. Activation of complement through deposition of C5b67 complexes on
      endothelial cells resulted in a small increase (approximately 20%) in PG binding.
      Incorporation of C8 into C5b-8 resulted in no further increase in binding;
      however, specific 125I-PG binding was increased by approximately 100% after C5b-9
      deposition. Moreover, PG was found to bind specifically to C7 and C9. The PG
      bound to endothelial cells after C5b-9 deposition was readily activated by tissue
      type plasminogen activator (TPA). In a cell-free system, complement C9 and a
      synthetic peptide composed of the 20 carboxyl-terminal amino acids of C9 enhanced
      PG activation by TPA. Removal of the carboxyl-terminal lysine of C9 abolished the
      enhancement of PG activation without diminishing PG binding. We conclude that
      membrane C9 may comprise a binding site for PG and serve to enhance activation of
      this zymogen by TPA. These findings suggest that immune injury to the endothelium
      may enhance both the fibrin-generating and fibrinolytic capacity of the vessel
      wall.

PMID- 9012653
TI  - Syndecan-4 is a primary-response gene induced by basic fibroblast growth factor
      and arterial injury in vascular smooth muscle cells.
AB  - Syndecans are a family of transmembrane proteoglycans that have been implicated
      in cell-extracellular matrix adhesion and growth factor binding. We reported
      previously that syndecan-1 expression by cultured rate vascular smooth muscle
      cells (VSMCs) is induced by serum- or platelet-derived growth factor (PDGF). We
      now report that syndecan-4 mRNA is rapidly induced in cultured VSMCs in response
      to basic fibroblast growth factor (bFGF) or serum stimulation. In the presence of
      cycloheximide, induction of syndecan-4 mRNA was enhanced. These characteristics
      identified syndecan-4 as a primary-response gene product in VSMCs. In contrast,
      syndecan-1 mRNA expression in response to serum was completely blocked in the
      presence of cycloheximide. We also examined the expression of syndecan mRNAs in
      VSMCs in response to balloon catheter injury in vivo. A reverse transcriptase
      polymerase chain reaction technique was developed that enabled us to amplify all
      four syndecan mRNAs in a single reaction tube and determine relative changes in
      their expression. All four syndecan mRNAs were detected in uninjured rat carotid
      arteries. In endothelium-denuded arteries, the medial layer (presumably VSMCs)
      accounted for 70% to 90% of the syndecan mRNAs in the vessel wall. The levels of
      syndecan-2 and syndecan-3 mRNAs were not altered significantly after balloon
      injury. In contrast, syndecan-4 mRNA was increased at early times after injury
      but then decreased to control level by 7 days. Syndecan-1 mRNA levels showed a
      slower but prolonged increase that reached a maximum at 7 days after injury.
      Immunostaining with anti-syndecan-4 antibodies demonstrated a rapid increase in
      syndecan-4 proteoglycan expression in the injured carotid artery.

PMID- 9012654
TI  - Localization of lipoprotein(a) in a monkey model of rapid neointimal growth.
AB  - Lipoprotein(a) [Lp(a)] has been proposed as a restenosis risk factor, but it is
      not known if Lp(a) is present in the injured arterial wall during the initial
      neointimal growth. The purpose of this study was to determine if Lp(a) is
      incorporated into the vessel wall during rapid neointimal formation after
      arterial injury in primates. In this model, distention of the iliac artery with
      an angioplasty catheter caused focal breaks in the internal elastic lamina (IEL)
      in 80% of the vessels and extensive IEL fragmentation with medial disruption in
      20% of the vessels. Neointimal growth was noted in all injured arteries; thrombus
      formation was noted in 40% of the vessels. Based on morphometric measurements,
      injured arteries had neointimal areas of 0.41 +/- 0.05 (n = 4) and 0.83 +/- 0.23
      (n = 6) mm2 at 14 and 28 days after injury, respectively. Control arteries had an
      intact IEL and a monolayer of intimal cells. Lp(a) localization was examined
      histologically by using a mouse monoclonal anti-Lp(a) antibody. Lp(a), found in
      all injured arteries, was localized primarily in the neointima in 50% of the
      vessels. In the subset of vessels with evidence of thrombus formation, intense
      Lp(a) immunostaining was associated with the thrombus. Lp(a) was specific to
      injured arteries as uninjured vessels did not stain. In addition, staining was
      not seen with a negative control, a nonspecific mouse IgG1 antibody. The presence
      of Lp(a) at the site of rapid neointimal growth supports a role for this
      lipoprotein in the response to vascular injury after balloon angioplasty.

PMID- 9012655
TI  - Neutralizing antibodies directed against osteopontin inhibit rat carotid
      neointimal thickening after endothelial denudation.
AB  - Osteopontin is an arginine-glycine-aspartate-containing acidic glycoprotein with
      adhesive and migratory activities in vitro. We previously showed that osteopontin
      was highly expressed in injured rat arteries as well as in human atherosclerotic
      plaques. In contrast, uninjured blood vessels make very little osteopontin. In
      this report, we have investigated the role of osteopontin in rat neointima
      formation using neutralizing antibodies. Rats were treated with either nonimmune
      or antiosteopontin antibody and subjected to endothelial denudation of the
      carotid artery by using a balloon catheter. Two weeks after injury, intimal areas
      and cell numbers were significantly decreased (33% and 31%, respectively) in the
      antiosteopontin group compared with the nonimmune IgG group. No differences in
      carotid medial areas or cell numbers were observed. Intimal and medial
      replication rates, as measured by continuous bromodeoxyuridine infusion during
      the final week of the experimental protocol, were not significantly different
      between the two groups. No gross histological changes were noted in the intimas
      formed in the presence of either neutralizing or nonimmune antibody. In addition,
      no difference in early carotid medial cell replication rate was observed when
      antibodies were infused for 4 days after angioplasty. These data demonstrate for
      the first time a functional role for osteopontin in the process of carotid
      neointimal thickening in vivo and suggest that osteopontin plays an active role
      in the remodeling processes important for human atherosclerotic and restenotic
      lesion development.

PMID- 9012656
TI  - Inhibition of collagen synthesis, smooth muscle cell proliferation, and injury
      induced intimal hyperplasia by halofuginone.
AB  - Proliferation of vascular smooth muscle cells (SMCs) and accumulation of
      extracellular matrix (ECM) components within the arterial wall in response to
      local injury are important etiologic factors in vascular proliferative disorders
      such as arteriosclerosis and restenosis after angioplasty. Fibrillar and
      nonfibrillar collagens are major constituents of the ECM that modulate cell shape
      and proliferative responses and thereby contribute to the pathogenesis of intimal
      hyperplasia. Halofuginone, an anticoccidial quinoazolinone derivative, inhibits
      collagen type I gene expression. We investigated the effect of halofuginone on
      (1) proliferation of bovine aortic endothelial cells and SMCs derived from the
      same specimen and maintained in vitro, (2) ECM deposition and collagen type I
      synthesis and gene expression, and (3) injury-induced intimal hyperplasia in
      vivo. DNA synthesis and proliferation of vascular SMCs in response to serum or
      basic fibroblast growth factor were abrogated in the presence of as little as 0.1
      microgram/mL halofuginone; this inhibition was reversible upon removal of the
      compound. Under the same conditions, halofuginone exerted a relatively small
      antiproliferative effect on the respective vascular endothelial cells.
      Halofuginone also inhibited the synthesis and deposition of ECM components by
      vascular SMCs as indicated both by a substantial reduction in the amount of
      sulfated proteoglycans and collagen type I synthesis and gene expression. Local
      administration of halofuginone in the rabbit ear model of crush injury-induced
      arterial intimal hyperplasia resulted in a 50% reduction in intimal thickening as
      measured by a morphometric analysis of the neointima/media ratio. The
      differential inhibitory effect of halofuginone on vascular SMCs versus
      endothelial cells, its inhibition of ECM deposition and collagen type I
      synthesis, and its ability to attenuate injury-induced intimal hyperplasia may
      place halofuginone alone or in combination with other antiproliferative compounds
      as a potential candidate for prevention of arterial stenosis and accelerated
      atherosclerosis.

PMID- 9012657
TI  - Plasma kinetics of cholesteryl ester transfer protein in the rabbit. Effects of
      dietary cholesterol.
AB  - The plasma kinetics of recombinant human cholesteryl ester transfer protein
      (rCETP) were studied in six rabbits before and after cholesterol feeding (0.5%
      wt/wt). The rCETP, labeled with the use of the Bolton Hunter reagent, was shown
      to retain neutral lipid transfer activity. After intravenous infusion, labeled
      rCETP associated with rabbit lipoproteins to an extent similar to endogenous
      rabbit CETP (62% to 64% HDL associated). The plasma kinetics of CETP, modeled
      with the use of SAAM-II, conformed to a two-pool model, likely representing free
      and loosely HDL-associated CETP (fast pool) and a tightly apo (apolipoprotein) AI
      associated (slow pool) CETP. The plasma residency time (chow diet) of the fast
      pool averaged 7.1 hours and of the slow pool, 76.3 hours. The production rate
      (PR) into and the fractional catabolic rate (FCR) of the fast pool were 20 and 10
      times the PR and FCR, respectively, of the slow pool. In response to cholesterol
      feeding, CETP PR, FCR, and plasma mass increased by 416%, 60%, and 230%,
      respectively. There was a strong correlation (r = .95, P = .003) between the
      increase in rabbit plasma CETP and the modeled increase in CETP PR in response to
      cholesterol feeding, suggesting that labeled human rCETP is a satisfactory tracer
      for rabbit plasma CETP. CETP is catabolized by distinct pools, likely
      corresponding to an apo AI-associated (slow) pool and a free and/or loosely HDL
      associated (fast) pool. Factors that alter the affinity of CETP for HDL would be
      predicted to result in altered CETP catabolism. The effect of dietary cholesterol
      on plasma CETP mass can be explained largely by the effects on CETP synthesis,
      consistent with the observed effects of cholesterol on tissue mRNA levels.

PMID- 9012658
TI  - Effect of the ACAT inhibitor CL 277,082 on apolipoprotein B48 transport in
      mesenteric lymph and on plasma clearance of chylomicrons and remnants.
AB  - Inhibitors of acyl CoA:cholesterol acyltransferase (ACAT) activity previously
      have been found to decrease the absorption of cholesterol and to be effective
      antiatherosclerotic agents. Effects on chylomicron (CM) transport could
      contribute to these effects. No previous study has examined the effect of
      inhibition of ACAT activity on the intestinal lymph output of apolipoprotein
      (apo) B48 or on the clearance from plasma of lymph CM. In this study, we selected
      2,4-difluoro-phenyl-N[[4-(2,2-dimethylpropyl)phenyl]methyl]-N-( hepthyl)urea (CL
      277,082) to inhibit intestinal ACAT activity and measured its effects on the
      output of lipids and apo B48 in intestinal lymph. Compared with control untreated
      rats, treatment with CL 277,082 decreased the lymph outputs of apo B48 and
      triglyceride. Associated with the effects on transport, the lymph CM were smaller
      in diameter in rats treated with CL 277,082. The unesterified cholesterol content
      of lymph CM was markedly increased and the cholesteryl ester (CE) content was
      decreased. The contents of triglyceride were decreased and phospholipid was
      increased. Labeled CM were prepared by feeding donor rats with a test meal
      containing 3H-cholesterol and 14C-fatty acid. Traced by the CE label in lymph CM
      in both control rats and rats treated with CL 277,082, the remnants derived after
      intravenous injection of CM from rats treated with CL 277,082 were cleared
      significantly more slowly than CM from untreated rats. Moreover, less CE label
      was recovered in the livers of both groups of rats after injection of CM from
      rats treated with CL 277,082. Recovery in the spleen was significantly higher in
      recipient rats injected with CM from rats treated with CL 277,082 when compared
      with injections of CM obtained from untreated rats. We conclude that the
      metabolism of CM is affected by treatment with CL 277,082, partly due to the
      changes in lymph CM composition and partly due to other effects on the recipient
      rat.

PMID- 9012659
TI  - Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine
      estrogens on coronary artery atherosclerosis.
AB  - Although estrogen replacement therapy is associated with reduced risk of coronary
      heart disease and reduced extent of coronary artery atherosclerosis, the effects
      of combined (estrogen plus progestin) hormone-replacement therapy are uncertain.
      Some observational data indicate that users of combined hormone replacement
      consisting of continuously administered oral conjugated equine estrogens (CEE)
      and oral sequentially administered (7 to 14 days per month) medroxyprogesterone
      acetate (MPA) experience a reduction in risk similar to that of users of CEE
      alone. However, the effects of combined, continuously administered CEE plus MPA
      (a prescribing pattern that has gained favor) on the risk of coronary heart
      disease or atherosclerosis are not known. We studied the effects of CEE (monkey
      equivalent of 0.625 mg/d) and MPA (monkey equivalent of 2.5 mg/d), administered
      separately or in combination, on the extent of coronary artery atherosclerosis
      (average plaque size) in surgically postmenopausal cynomolgus monkeys fed
      atherogenic diets and treated with these hormones for 30 months. Treatment with
      CEE alone resulted in atherosclerosis extent that was reduced 72% relative to
      untreated (estrogen-deficient) controls (P < .004). Atherosclerosis extent in
      animals treated with CEE plus MPA or MPA alone did not differ from that of
      untreated controls. Although treatment had marked effects on plasma lipoprotein
      patterns, statistical adjustment for variation in plasma lipoproteins did not
      alter the between-group relationships in atherosclerotic plaque size, suggesting
      that these factors do not explain substantially the atheroprotective effect of
      estrogen or the MPA-associated antagonism. Although the mechanism(s) remains
      unclear, we conclude that oral CEE inhibits the initiation and progression of
      coronary artery atherosclerosis and that continuously administered oral MPA
      antagonizes this atheroprotective effect.

PMID- 9012660
TI  - Distal apolipoprotein C-III regulatory elements F to J act as a general modular
      enhancer for proximal promoters that contain hormone response elements. Synergism
      between hepatic nuclear factor-4 molecules bound to the proximal promoter and
      distal enhancer sites.
AB  - Transient transfection assays have shown that the distal apoC-III promoter
      segments that contain the regulatory elements F to J enhance the strength of the
      tandemly linked proximal apoA-I promoter 5- to 13-fold in hepatic (HepG2) cells.
      Activation in intestinal (CaCo-2) cells to levels comparable to those obtained in
      HepG2 cells requires a larger apoA-I promoter sequence that extends to nucleotide
      -1500 as well as the presence of hepatic nuclear factor-4 (HNF-4). The distal
      apoC-III regulatory elements can also enhance 4- to 8-fold the strength of the
      heterologous apoB promoter in HepG2 and CaCo-2 cells. Finally, these elements in
      the presence of HNF-4 enhance 14.5- to 18.5-fold the strength of the minimal
      adenovirus major late promoter linked to two copies of the hormone response
      element (HRE) AID of apoA-I in both HepG2 and CaCo-2 cells. In vitro mutagenesis
      of the promoter/enhancer cluster established that the enhancer activity is lost
      by a mutation in the HRE present in the 3' end of the regulatory element I (-736
      to -714) and is reduced significantly by point mutations or deletions in one or
      more of the regulatory elements F to J of the apoC-III enhancer. The enhancer
      activity also requires the HREs of the proximal apoA-I promoter. The apoC-III
      enhancer can also restore the activity of the proximal apoA-I and apoB promoters
      that have been inactivated by mutations in CCAAT/enhancers binding protein
      binding sites, indicating that C/EBP may not participate in the synergistic
      activation of the promoter/enhancer cluster. The findings suggest that the
      regulatory elements F to J of the apoC-III promoter act as a general modular
      enhancer that can potentiate the strength of proximal promoters that contain
      HREs. Such potentiation in the HepG2 cells can be accounted for by synergistic
      interactions between HNF-4 or other nuclear hormone receptors bound to the
      proximal and distal HREs and SP1 or other factors bound to the apoC-III enhancer.
      Additional factors may be required for optimal activity in CaCo-2 cells as well
      as for the function of this region as an intestinal enhancer.

PMID- 9012661
TI  - Escherichia coli RNA polymerase activity observed using atomic force microscopy.
AB  - Fluid tapping-mode atomic force microscopy (AFM) was used to observe Escherichia
      coli RNA polymerase (RNAP) transcribing two different linear double-stranded (ds)
      DNA templates. The transcription process was detected by observing the
      translocation of the DNA template by RNAP on addition of ribonucleoside 5'
      triphosphates (NTPs) in sequential AFM images. Stalled ternary complexes of RNAP,
      dsDNA and nascent RNA were adsorbed onto a mica surface and imaged under
      continuously flowing buffer. On introduction of all four NTPs, we observed some
      DNA molecules being pulled through the RNAP, some dissociating from the RNAP and
      others which did not move relative to the RNAP. The transcription rates were
      observed to be approximately 0.5-2 bases/s at our NTP concentrations,
      approximately 5 microM. The RNA transcripts were not unambiguously imaged in
      fluid. However, in experiments using a small single-stranded (ss) circular DNA
      template, known as a rolling circle, transcripts up to 1 or 2 microns long could
      be observed with tapping mode AFM once the samples were dried and imaged in air.
      This confirmed our observations of the transcriptional activity of RNAP adsorbed
      onto mica. This work illustrates that the development of tapping-mode in fluid
      has made it possible to use AFM to follow biological processes at the molecular
      level and get new insights about the variability of activity of individual
      molecules bound to a surface.

PMID- 9012662
TI  - Histones in transit: cytosolic histone complexes and diacetylation of H4 during
      nucleosome assembly in human cells.
AB  - The organization and acetylation of nascent histones prior to their stable
      incorporation into chromatin were examined. Through sedimentation and
      immunoprecipitation analyses of HeLa cytosolic extracts, two somatic non
      nucleosomal histone complexes were detected: one containing nascent H3 and H4,
      and a second containing H2A (and probably H2B) in association with the nonhistone
      protein NAP-1. The H3/H4 complex has a sedimentation coefficient of 5-6S,
      consistent with the presence of one or more escort proteins. H4 in the cytosolic
      H3/H4 complex is diacetylated, fully in accord with the acetylation state of
      newly synthesized H4 in chromatin. The diacetylation of nascent human H4 is
      therefore completed prior to nucleosome assembly. As part of our studies of the
      nascent H3/H4 complex, the cytoplasmic histone acetyltransferase most likely
      responsible for acetylating newly synthesized H4 was also investigated. HeLa
      histone acetyltransferase B (HAT B) acetylates H4 but not H3 in vitro, and
      maximally diacetylates H4 even in the presence of sodium butyrate. Human HAT B
      acetylates H4 exclusively on the lysine residues at positions 5 and 12, in
      complete agreement with the highly conserved acetylation pattern of nascent
      nucleosomal H4 (Sobel et al., 1995), and has a native molecular weight of
      approximately 100 kDa. Based on our findings a model is presented for the
      involvement of histone acetylation and NAP-1 in H2A/H2B deposition and exchange,
      during nucleosome assembly and chromatin remodeling in vivo.

PMID- 9012663
TI  - Crystal structure of nucleotide-free diphtheria toxin.
AB  - The crystal structure of diphtheria toxin (DT) in the absence of nucleotide
      (nucleotide-free DT) has been determined at 2.3 A resolution to a
      crystallographic R factor and free R factor of 18.2 and 28.2%, respectively. A
      comparison of this structure to the previously determined structures of DT in
      complex with adenyly(3'-5')uridine monophosphate (ApUp) and DT in complex with
      nicotinamide adenine dinucleotide (NAD) reveals that there are no significant
      movements of the two subdomains of the catalytic (C) domain associated with
      dinucleotide binding. The side chains of six residues within the active-site
      cleft, including Tyr65, Pro38, Tyr27, Thr23, Glu148, and Tyr54, show movements of
      up to 3 A upon dinucleotide binding. In the structure of nucleotide-free DT, the
      active-site loop residues 39-47 of the C domain are well ordered and extend over
      the active-site cleft in approximately the same position as in the structure of
      DT in complex with ApUp. This is in contrast to the structure of the DT-NAD
      complex, in which the active-site loop is disordered. On the basis of a
      comparison of the nucleotide-free and NAD-bound DT structures, we suggest that
      the interaction of NAD with Pro38 and also possibly Tyr54 and Trp153 could
      disrupt the network of hydrogen bonds that stabilizes the position of the active
      site loop over the active-site cleft, allowing this loop to become disordered.
      This may be an important step in binding of the C domain of DT to its substrate,
      elongation factor-2.

PMID- 9012664
TI  - Three-dimensional structure of tetrahydrodipicolinate N-succinyltransferase.
AB  - The conversion of tetrahydrodipicolinate and succinyl-CoA to N
      succinyltetrahydrodipicolinate and CoA is catalyzed by tetrahydrodipicolinate N
      succinyltransferase and is the committed step in the succinylase pathway by which
      bacteria synthesize L-lysine and meso-diaminopimelate, a component of
      peptidoglycan. The X-ray crystal structure of THDP succinyltransferase has been
      determined to 2.2 A resolution and has been refined to a crystallographic R
      factor of 17.0%. The enzyme is trimeric and displays the left-handed parallel
      beta-helix (L beta H) structural motif encoded by the "hexapeptide repeat" amino
      acid sequence motif [Raetz, C.R.H., & Roderick, S.L. (1995) Science 270, 997
      1000]. The approximate location of the active site of THDP succinyltransferase is
      suggested by the proximity of binding sites for two inhibitors: p
      (chloromercuri)benzenesulfonic acid and cobalt ion, both of which bind to the L
      beta H domain.

PMID- 9012665
TI  - Solution structure of phenol hydroxylase protein component P2 determined by NMR
      spectroscopy.
AB  - Phenol hydroxylase from Pseudomonas sp. CF600 is a member of a family of
      binuclear iron-center-containing multicomponent oxygenases, which catalyzes the
      conversion of phenol and some of its methyl-substituted derivatives to catechol.
      In addition to a reductase component which transfers electrons from NADH, optimal
      turnover of the hydroxylase requires P2, a protein containing 90 amino acids
      which is readily resolved from the other components. The three-dimensional
      solution structure of P2 has been solved by 3D heteronuclear NMR spectroscopy. On
      the basis of 1206 experimental constraints, including 1060 distance constraints
      obtained from NOEs, 70 phi dihedral angle constraints, 42 psi dihedral angle
      constraints, and 34 hydrogen bond constraints, a total of 12 converged structures
      were obtained. The atomic root mean square deviation for the 12 converged
      structure with respect to the mean coordinates is 2.48 A for the backbone atoms
      and 3.85 A for all the heavy atoms. This relatively large uncertainty can be
      ascribed to conformational flexibility and exchange. The molecular structure of
      P2 is composed of three helices, six antiparallel beta-strands, one beta-hairpin,
      and some less ordered regions. This is the first structure among the known
      multicomponent oxygenases. On the basis of the three-dimensional structure of P2,
      sequence comparisons with similar proteins from other multicomponent oxygenases
      suggested that all of these proteins may have a conserved structure in the core
      regions.

PMID- 9012667
TI  - A conformational change in the catalytic core of the hammerhead ribozyme upon
      cleavage of an RNA substrate.
AB  - Heteronuclear multidimensional NMR structural studies have been performed on a
      hammerhead ribozyme complexed with a cleaved and an uncleaved substrate. The NMR
      data demonstrate that the three helices surrounding the conserved catalytic core
      hammerhead are stably formed in both complexes. Evidence is also presented that
      indicates that the sheared G-A base pairs in the conserved core are formed in the
      absence of Mg2+. The NMR structural data demonstrate that there is a significant
      structural change of the conserved core of the hammerhead ribozyme-substrate
      complex upon cleavage of the substrate. Molecular dynamics calculations were
      performed to generate models of the ribozyme-cleaved substrate complex, and these
      results are used to help understand the mechanism of the hammerhead cleavage
      reaction.

PMID- 9012666
TI  - Time-resolved fluorescence of intestinal and liver fatty acid binding proteins:
      role of fatty acyl CoA and fatty acid.
AB  - The effect of fatty acyl CoA and fatty acid on the solution structure and
      dynamics of two intestinal enterocyte fatty acid binding proteins, intestinal (I
      FABP) and liver (L-FABP), was examined by time-resolved fluorescence of FABP
      aromatic amino acid residues. I-FABP Trp displayed two rotational correlation
      times, 6.6 and 0.4 ns. reflecting motion of the protein as a whole and segmental
      mobility of Trp. Neither oleoyl CoA, oleic acid, nor CoASH altered overall I-FABP
      rotational correlation time. However, oleic acid and CoASH increased I-FABP Trp
      segmental mobility, while oleoyl CoA and CoASH decreased I-FABP Trp limiting
      anisotropy (order). The angle of I-FABP Trp "wobbling in a cone" was increased by
      ligands in the order oleoyl CoA > CoASH > oleic acid. L-FABP Trp segmental
      mobility. L-FABP overall rotational motion, in contrast to that of I-FABP, was
      significantly increased by ligands in the order oleoyl CoA > oleic acid > CoASH.
      cis-Parinaric acid and cis-parinaroyl CoA bound to L-FABP also reflected overall
      L-FABP motion but yielded longer rotational correlation times, 8.2 and 10.7 ns,
      than the respective apo-FABPs. Such effects were not observed with I-FABP.
      Finally, both cis-parinaric acid and cis-parinaroyl CoA were much less ordered in
      the I-FABP ligand binding site than with L-FABP. These observations suggest that
      the rotational dynamics of L-FABP and its conformation are more sensitive to
      ligands than I-FABP. Further, ligands such as fatty acids, fatty acyl CoAs,
      and/or CoASH differentially modulate the I-FABP and L-FABP dynamics, and the
      ligand binding sites of these proteins differ in their ability to order the
      ligands.

PMID- 9012668
TI  - Energetics of folding and DNA binding of the MAT alpha 2 homeodomain.
AB  - Homeodomains are a class of DNA-binding protein domains which play an important
      role in genetic regulation in eukaryotes. We have characterized the
      thermodynamics of folding and sequence-specific association with DNA of the MAT
      alpha 2 homeodomain of yeast. Using differential scanning and isothermal
      titration calorimetry, we measured the enthalpy, heat capacity, and Gibbs free
      energy changes of these processes. The protein-DNA interaction is enthalpically
      driven at physiological temperatures. DSC data on the process of melting the
      protein-DNA complex at different salt concentrations were dissected into its
      endothermic components, yielding the enthalpy change and dissociation constant of
      binding. A comparison of the circular dichroism spectra of the free and DNA-bound
      protein species revealed the formation of additional alpha-helical structure upon
      binding to DNA. We propose that the latter half of helix 3, the recognition
      helix, is substantially unfolded in the free protein under the conditions used,
      as has been observed with other homeodomains [Tsao, D. H. H., et al. (1994)
      Biochemistry 33, 15053-15060: Cox, M., et al. (1995) J. Biomol. NMR 5, 23-32].
      Formation of protein structure is induced by DNA binding, and the energies
      measured for association therefore include a component due to folding.

PMID- 9012669
TI  - Comparison of major groove hydration in isomorphous A-DNA octamers and dependence
      on base sequence and local helix geometry.
AB  - The family of ten isomorphous tetragonal A-DNA octamers provides a unique
      opportunity to examine major groove hydration in terms of base sequence and local
      parameter effects. The presence of a severely underwound central py.pu base step
      (average = 24.1 degrees), which lies on a crystallographic 2-fold in the unit
      cell, provides a sharp change in the local environment in which to study and
      separate the effects of base sequence and local helix geometry on major groove
      hydration. For this reason, and to avoid bias secondary to end effects, hydration
      analysis was restricted to the central four dyad-related base paris. This study
      finds that d(CG) base pairs are better hydrated than d(TA) base pairs, 2.5 H2O vs
      1.3 H2O; steps with high twist angles are better hydrated than steps with low
      twist angles, 6.9 H2O vs 0 H2O; negative roll angles are better hydrated than
      positive roll angles, 2.8 H2O vs 1.8 H2O; and flanking base pairs are better
      hydrated than central base pairs, 2.6 H2O vs 2.0 H2O, a phenomenon which is
      sequence independent, occurring for both d(CG) and d(TA) base pairs. The twist
      angle and base roll combine to significantly affect the pattern and degree of
      major groove hydration in this family of octamers. A previous study of A-DNA
      octamers and their helix parameters established a strong dependency on crystal
      packing forces with little or no dependence on the base sequence [Ramakrishnan &
      Sundaralingam (1993) J. Biomol. Struct. Dyn. 11. 11-26]. We find that the degree
      and pattern of major groove hydration are strongly influenced by the local helix
      parameters, implying an indirect, but significant, relationship between major
      groove hydration and environmental forces, i.e., crystal packing, drug binding,
      and protein-DNA interactions.

PMID- 9012670
TI  - The tyrosine photophysics of a primase-derived peptide are sensitive to the
      peptide's zinc-bound state: proof that the bacterial primase hypothetical zinc
      finger sequence binds zinc.
AB  - A 35-amino acid peptide corresponding to the putative "zinc finger" sequence of
      primase was prepared to study its zinc binding properties. When zinc was added to
      the peptide, it was found that the fluorescence quantum yield of the single
      tyrosine increased by 46% and the average lifetime by 34%. The binding
      stoichiometry was one zinc per peptide. Below pH 6.0 and above pH 8.5, the zinc
      peptide binding affinity was less than 1 microM and could be accurately
      determined. Interpolation from those binding constants suggested that the
      affinity at pH 7.5 was between 10 and 100 nM. The absorption spectrum of the
      cobalt(II)-peptide complex was consistent with tetrahedral metal coordination by
      three sulfur and one imidazole nitrogen ligands. The peptide affinity for cobalt
      was less than for zinc, indicating metal specificity. Analysis of the
      fluorescence intensity pH profile, circular dichroism spectra, the effect of
      extrinsic quenchers indicated that at neutral pH (1) the free peptide up into a
      structure to place the tyrosine in an environment protected from solvent, (2) the
      peptide bound zinc via its three cysteines and one of its histidines resulting in
      little change to the polypeptide secondary structure or to the tyrosine solvent
      accessibility, and (3) when the peptide bound zinc, it bound directly to or
      caused the immobilization of the groups that had been intramolecularly
      collisionally quenching the tyrosine which resulted in the observed increases in
      tyrosine quantum yield and lifetime.

PMID- 9012671
TI  - Mechanism of cytochrome c oxidase-catalyzed reduction of dioxygen to water:
      evidence for peroxy and ferryl intermediates at room temperature.
AB  - The reaction between bovine heart cytochrome oxidase and dioxygen was
      investigated at room temperature following photolysis of the fully reduced CO
      bound enzyme. Time-resolved optical absorption difference spectra were collected
      by a gated multichannel analyzer in the visible region (lambda = 460-720 nm) from
      50 ns to 50 ms after photolysis. Singular value decomposition (SVD) analysis
      indicated the presence of at least seven intermediates. Multiexponential fitting
      gave the following apparent lifetimes: 1.2 microseconds, 10 microseconds, 25
      microseconds, 32 microseconds, 86 microseconds, and 1.3 ms. On the basis of the
      SVD results and a double difference map, a sequential kinetic mechanism is
      proposed from which the spectra and time-dependent populations of the reaction
      intermediates were determined. The ferrous-oxy complex (compound A), with a peak
      at 595 nm and a trough at 612 nm versus the reduced enzyme, reaches a maximum
      concentration approximately 30 microseconds after photolysis. It decays to a 1:6
      mixture of peroxy species (a3(3+)-O(-)-O-) in which cytochrome a is reduced and
      oxidized. Cytochrome a3 in both species has a peak at 606 nm versus its oxidized
      form. The peroxy species decay to a ferryl intermediate, with a peak at 578 nm
      versus the oxidized enzyme, followed by electron redistribution between CuA and
      cytochrome a. The two ferryl species reach a maximum concentration approximately
      310 microseconds after photolysis. The excellent agreement between the
      experimental and theoretical spectra of the intermediates provides unequivocal
      evidence for the presence of peroxy and ferryl species during dioxygen reduction
      by cytochrome oxidase at room temperature.

PMID- 9012672
TI  - NMR study of the conformation of galactocerebroside in bilayers and solution:
      galactose reorientation during the metastable-stable gel transition.
AB  - Conformations of two types of bovine brain cerebroside containing normal and
      alpha-hydroxy-fatty acids (NFA-CER and HFA-CER, respectively) in solution and in
      bilayers were investigated using 1H and 13C NMR in solution and in the solid
      state. The analysis of vicinal 1H-1H coupling constants and NOE measurements in
      solution indicated that in both cerebrosides the predominant conformation about
      the O1-C1, C1-C2, and C2-C3 bonds is ap/-sc/ap, respectively. The remarkable
      similarity in the 13C NMR chemical shifts in solution and in hydrated liquid
      crystalline bilayers indicated that both cerebrosides in bilayers assume
      conformation essentially identical to those in solution. The obtained 13C NMR
      spectra in solution were used as a reference for comparison with the variable
      temperature 13C CP-MAS NMR spectra in the metastable and stable gel phases. The
      lack of chemical shift changes of polar carbon atoms upon cooling the HFA-CER
      bilayers below the Tm strongly suggests that the liquid-crystalline-metastable
      gel transition is not associated with a conformational change of the head group.
      The observed line broadening can be interpreted in terms of the hydrocarbon chain
      crystallization and slow dynamics of the head group in the metastable phase. On
      the other hand, the relaxation of the metastable gel phase of HFA-CER caused
      profound changes in the 13C spectra, primarily of the signals of the galactose
      C1, the ceramide C2, C4, and C5, and the carbonyl group. These changes are
      interpreted using the known dependence of the chemical shifts of anomeric carbon
      on the conformation about the O1-C1 bond to suggest that the gel phase relaxation
      involves a significant reorientation of the galactose moiety caused by a change
      in the rotation of the O1-C1 bond from the ap to -sc conformer. Similar changes
      of chemical shifts were observed in the case of NFA-CER during the transition
      from the liquid-crystalline phase to the stable gel phase.

PMID- 9012673
TI  - The three-dimensional structure of the human Pi class glutathione transferase P1
      1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate.
AB  - The potent diuretic drug ethacrynic acid has been tested in clinical trials as an
      adjuvant in chemotherapy. Its target is the detoxifying enzyme glutathione
      transferase which is often found overexpressed in cancer tissues. We have solved
      the crystal structures of human pi class glutathione transferase P1-1 in complex
      with the inhibitor ethacrynic acid and its glutathione conjugate. Ethacrynic acid
      is found to bind in a nonproductive mode to one of the ligand binding sites of
      the enzyme (the H site) while the glutathione binding site (G site) is occupied
      by solvent molecules. There are no structural rearrangements of the G site in the
      absence of ligand. The structure indicates that bound glutathione is required for
      ethacrynic acid to dock into the H site in a productive binding mode. The binding
      of the ethacrynic acid-glutathione conjugate shows that the contacts of the
      glutathione moiety with the protein are identical to those observed in crystal
      structures of the enzyme with other glutathione-based substrates and inhibitors.
      The ethacrynic acid moiety of the conjugate binds in the H site in a fashion that
      has not been observed in crystal structures of other glutathione-based inhibitor
      complexes. The crystal structures implicate Tyr 108 as an electrophilic
      participant in the Michael addition of glutathione to ethacrynic acid.

PMID- 9012674
TI  - Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate
      reductase: crystallographic evidence.
AB  - The reaction catalyzed by Escherichia coli dihydrofolate reductase (ecDHFR)
      cycles through five detectable kinetic intermediates: holoenzyme, Michaelis
      complex, ternary product complex, tetrahydrofolate (THF) binary complex, and
      THF.NADPH complex. Isomorphous crystal structures analogous to these five
      intermediates and to the transition state (as represented by the methotrexate
      NADPH complex) have been used to assemble a 2.1 A resolution movie depicting loop
      and subdomain movements during the catalytic cycle (see Supporting Information).
      The structures suggest that the M20 loop is predominantly closed over the
      reactants in the holoenzyme, Michaelis, and transition state complexes. But,
      during the remainder of the cycle, when nicotinamide is not bound, the loop
      occludes (protrudes into) the nicotinamide-ribose binding pocket. Upon changing
      from the closed to the occluded conformation, the central portion of the loop
      rearranges from beta-sheet to 3(10) helix. The change may occur by way of an
      irregularly structured open loop conformation, which could transiently admit a
      water molecule into position to protonate N5 of dihydrofolate. From the Michaelis
      to the transition state analogue complex, rotation between two halves of ecDHFR,
      the adenosine binding subdomain and loop subdomain, closes the (p
      aminobenzoyl)glutamate (pABG) binding crevice by approximately 0.5 A. Resulting
      enhancement of contacts with the pABG moiety may stabilize puckering at C6 of the
      pteridine ring in the transition state. The subdomain rotation is further
      adjusted by cofactor-induced movements (approximately 0.5 A) of helices B and C,
      producing a larger pABG cleft in the THF.NADPH analogue complex than in the THF
      analogue complex. Such movements may explain how THF release is assisted by NADPH
      binding. Subdomain rotation is not observed in vertebrate DHFR structures, but an
      analogous loop movement (residues 59-70) appears to similarly adjust the pABG
      cleft width, suggesting that these movements are important for catalysis. Loop
      movement, also unobserved in vertebrate DHFR structures, may preferentially
      weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce
      product inhibition in the NADP+ rich environment of prokaryotes.

PMID- 9012675
TI  - Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: a
      binding mechanism for recombinant enzyme.
AB  - Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase (DMAPP
      tRNA transferase) catalyzes the first step in the biosynthesis of the
      hypermodified A37 residue in tRNAs that read codons beginning with uridine. The
      enzyme, encoded by the miaA gene, was overproduced and purified to apparent
      homogeneity in three steps by ion-exchange (DE52 and Mono-Q) and size exclusion
      chromatography. Affinity-tagged DMAPP-tRNA transferase containing a C-terminal
      tripeptide alpha-tubulin epitope also was overproduced and purified to apparent
      homogeneity in two steps by ion-exchange and immunoaffinity chromatography.
      Addition of the C-terminal tripeptide alpha-tubulin epitope to DMAPP-tRNA
      transferase did not affect the activity of the enzyme. Undermodified tRNA(Phe)
      used as substrate in the DMAPP-tRNA transferase-catalyzed reaction was isolated
      and purified from an overexpressing clone in a miaA deficient strain of E. coli.
      Active recombinant E. coli DMAPP-tRNA transferase is monomeric. The enzyme
      transferred the dimethylallyl moiety of DMAPP to A37, located adjacent to the
      anticodon in undermodified tRNA(Phe). The enzyme required Mg2+ for activity and
      exhibited a broad pH optimum. Michaelis constants for tRNA(Phe) and DMAPP are 96
      +/- 11 nM and 3.2 +/- 0.5 microM, respectively, and Vmax = 0.83 +/- 0.02 micromol
      min-1 mg-1. DMAPP-tRNA transferase bound tRNA(Phe) with a dissociation constant
      of 5.2 +/- 1.2 nM. In contrast, DMAPP did not bind to the enzyme in the absence
      of tRNA. However, DMAPP was bound with a dissociation constant of 3.4 +/- 0.6
      microM in the presence of a minihelix analogue of the anticodon stem-loop of
      tRNA(Phe) where the base corresponding to A37 was replaced by inosine. These
      results suggest an ordered sequential mechanism for substrate binding.

PMID- 9012676
TI  - Use of 1H-15N heteronuclear multiple-quantum coherence NMR spectroscopy to study
      the active site of aspartate aminotransferase.
AB  - Aspartate aminotransferase from Escherichia coli, an 88 kDa enzyme, was uniformly
      and selectively enriched with 15N and was studied by heteronuclear multiple
      quantum coherence NMR spectroscopy in H2O. Good resolution was obtained for the
      downfield region (above 9.5 ppm chemical shift in the 1H dimension) for NH
      protons in the amide, indole, imidazole, and guanidinium group regions and
      several resonances were tentatively assigned. Two downfield resonances, at 12.6
      and 11.36 ppm, appear to belong to oxygen- or sulfur-bound protons. The most
      downfield amide resonance at 11.78 ppm was assigned to the active site cysteine
      192 whose peptide proton is 2.9 A away from the negatively charged carboxyl group
      of aspartate 199. Large downfield shifts (up to 1.15 ppm) of the indole NH
      resonance of the active site tryptophan 140 were observed upon binding of
      dicarboxylic inhibitors to the pyridoxal 5'-phosphate (PLP) form and of inorganic
      dianions to the pyridoxamine 5'-phosphate (PMP) form of the enzyme. We discuss
      these striking differences in the light of the available crystallographic data.
      Active sites of proteins, as well as specific inhibitory molecules, often contain
      negatively charged groups. These may be able to form hydrogen-bonds to NH groups
      and to shift the NH resonances downfield into a less crowded and therefore more
      readily observable region for many large proteins. Our approach, which makes use
      of both HMQC spectroscopy and NOE observations, should be widely applicable.

PMID- 9012677
TI  - Guanine nucleotide binding properties of Rac2 mutant proteins and analysis of the
      responsiveness to guanine nucleotide dissociation stimulator.
AB  - The Rac GTPases are currently being subjected to intensive study due to their
      involvement in a wide array of cellular phenomena. Many studies of Rac function
      have relied upon the use of relatively uncharacterized Rac dominant active,
      dominant negative, and effector domain mutants on the basis of the analogy to Ras
      structure. We have generated and purified such Rac2 mutants and characterized
      their guanine nucleotide binding properties in vitro. The Rac2 G12V and Q61L
      activating mutations were shown to hydrolyze bound GTP very slowly and were
      unresponsive to p190 Rac GTPase-activating protein. Distinct differences in the
      kinetics of nucleotide binding to individual mutant proteins were observed,
      accounting for the behavior of these proteins in biological assays. The
      structural features required for the responsiveness of Rac2 to the guanine
      nucleotide exchange protein smgGDS were examined. We show that guanine nucleotide
      exchange by smgGDS is dependent upon intact switch 1 and switch 2 regions in
      Rac2. Functional interactions between the switch 1 and switch 2 regions and the
      G12V mutation of Rac2 are described. These data form the basis for rational use
      of Rac mutants in biological studies.

PMID- 9012679
TI  - Spectroscopic evidence for a conformational transition in horseradish peroxidase
      at very low pH.
AB  - Resonance Raman (RR), electronic absorption, and circular dichroism (CD)
      spectroscopies of the ferric, ferrous, and ferrous-CO forms of horseradish
      peroxidase (HRP-C) at pH 3.1 are reported. The CD spectra in the UV region show
      only a small decrease in the alpha-helical content upon pH lowering, whereas
      dramatic changes are observed in the Soret region. The final form of ferric HRP-C
      is 5-coordinate high-spin heme whose histidine ligand is replaced by a water
      ligand with a polar character. The electronic and CD spectra show the presence of
      an intermediate form with a 6-coordinate heme. Therefore, the cleavage of the
      proximal Fe-imidazole bond is preceded by the binding of a distal water molecule.
      For the ferrous form of HRP-C, the pH-dependence of the absorption spectra
      revealed only the native form in the range pH 5-7 and an unfolded form with a
      Soret maximum at 383 nm at pH 3.1. An intermediate state, characterized by a
      Soret maximum at 424 nm, was observed only in a transient way, within a few
      milliseconds. A metastable and a final species are observed also for the ferrous
      CO complex at pH 3.1, as proved by isosbestic points in the electronic absorption
      spectra. The two forms show different RR nu(Fe-C) and IR nu(CO) modes. The
      metastable form corresponds to a heme where histidine is replaced by water. The
      final form is due to the displacement of the water ligand by the proximal
      histidine. We propose a kinetic model to account for our results at pH 3.1 for
      the ferric, ferrous, and ferrous-CO forms.

PMID- 9012678
TI  - Synergism of constitutive activity in alpha 1-adrenergic receptor activation.
AB  - Recently a number of mutations have been found in vitro which maintain alpha 1
      adrenergic receptors (ARs) in a partially activated form. We have previously
      identified two amino acid residue positions in the alpha 1b-adrenergic receptor
      (AR), Cys128 and Ala204, one in each of the third and fifth transmembrane
      segments, that constitutively activate the receptor when substituted for a
      phenylalanine or valine, respectively [Perez et al. (1996) Mol. Pharmacol. 49,
      112-122; Hwa et al. (1996) J. Biol. Chem. 271, 7956-7964]. Another mutation
      analyzed previously, Ala293Glu, located in the third intracellular loop, also
      constitutively activates the receptor [Kjelsborg et al. (1992) J. Biol. Chem.
      267, 1430-1433]. All three mutations displayed similar manifestations of
      constitutive activity such as higher binding affinity and potency for agonists as
      well as higher basal signal transduction as predicted by the revised ternary
      complex model of receptor activation. We hypothesized that the individual
      mutations because of their critical location alter the conformation of the
      transmembrane helices such that mimicry occur that partially conforms to the
      activated state, R*. To explore whether these potential conformations are
      independent, we combined these three mutations in all possible permutations. The
      combined triple mutation displays 700-fold higher binding affinity for (-)
      epinephrine and 20-fold higher basal IP3 release than the wild-type receptor. We
      also observed that each mutation contributed independently and synergistically to
      both receptor agonist binding and activation with the combined mutations basal
      activity exceeding that of the fully-stimulated wild-type receptor. There was
      also a direct correlation between epinephrine's binding affinity and the degree
      of constitutive activity. Because the mutations affect different transmembrane
      domains, these results are consistent with a mechanism that helical movement acts
      in a concerted fashion in agonist-induced activation, a synergism predicted if
      multiple helix movement is involved in receptor activation.

PMID- 9012680
TI  - Structural RNA mimetics: N3'-->P5' phosphoramidate DNA analogs of HIV-1 RRE and
      TAR RNA form A-type helices that bind specifically to Rev and Tat-related
      peptides.
AB  - An attractive strategy for the development of anti-retroviral drugs is the
      exploration of compounds that mimic RNA control regions of the viral genome and
      act as "decoys" to sequester viral gene regulatory proteins. Decoys consisting of
      RNA, however, are chemically unstable and readily degraded by cellular nucleases.
      DNA decoys, which are slightly more stable, also might not be appropriate because
      of possible structural differences between RNA and DNA helices and the complexes
      they form with proteins. It was recently reported, however, that DNA analogs with
      modified N3'-->P5' phosphoramidate sugar-phosphate backbones are stable and
      nuclease-resistant and exist predominately as A-form helices in solution
      [Gryaznov, S., et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 5798-5802]. We now
      report that oligonucleotide N3'-->P5' phosphoramidates DNA analogs of HIV-1 RRE
      IIB and TAR RNA form stable duplexes that exist in the A form as judged by
      circular dichroism (CD). Moreover, gel shift assays demonstrate that these
      phosphoramidates can specifically bind to peptides derived from HIV-1 Rev and Tat
      proteins. Isosequential phosphodiester DNA duplexes, existing in the B form by
      CD, do not bind to the respective peptides under the experimental conditions
      used. These results suggest the possibility that nuclease-resistant
      oligonucleotide N3'-->P5' phosphoramidates might serve as RNA-like decoys and
      disrupt specific viral RNA/protein interactions such as RRE/Rev and TAR/Tat in
      HIV-1.

PMID- 9012681
TI  - Conformational order of specific phospholipids in human erythrocytes:
      correlations with changes in cell shape.
AB  - Acyl chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) and
      dimyristoyphosphatidylserine (DMPS-d54) were incorporated into human
      erythrocytes. Light microscopy demonstrated that erythrocytes incubated with an
      equimolar mixture of DMPC-d54/DMPS or DMPC/DMPS-d54 remained mostly discocytic
      whereas cells incubated with either DMPC-d54 or DMPS-d54 alone became echinocytic
      or stomatocytic, respectively. Cells in which the aminophospholipid translocating
      protein was inhibited became echinocytic when incubated with DMPS-d54. Fourier
      transform infrared (FTIR) spectroscopy was used to monitor conformational order
      in the acyl chains of the incorporated phospholipid, as detected through the
      asymmetric CD2 stretching vibrations in the intact cells. In cells incubated with
      equimolar mixtures of DMPC-d54/DMPS or DMPC/DMPS-d54, the deuterated species
      exhibited no thermotropic phase transitions but revealed chain order intermediate
      between the gel and liquid-crystal states. In contrast, DMPS-d54 incorporated
      into the outer leaflet of echinocytic erythrocytes was conformationally ordered
      while the same species incorporated into the inner leaflet of stomatocytic
      erythrocytes was highly disordered at all temperatures studied. Finally, DMPC-d54
      incorporated into the outer leaflet of echinocytic erythrocytes exhibited a phase
      transition, suggesting that this species persists in domains. These data indicate
      that the acyl chain conformational order of specific phospholipids in the intact
      human erythrocyte is changed with alterations in cell morphology.

PMID- 9012682
TI  - Lineage specificity in haematological neoplasms.

PMID- 9012683
TI  - Body iron stores in relation to growth and pubertal maturation in healthy boys.
AB  - During male puberty, erythropoiesis is exceptionally active. Pubertal development
      and iron status were followed in 60 healthy boys at 3-month intervals for 24
      months to evaluate changes in body iron stores with the serum transferrin
      receptor-ferritin ratio. The estimated amount of stored iron declined by about
      50% over a 2-year period. Remarkable changes in iron stores were found even after
      as short an interval as 3 months and pubertal development was closely linked with
      a decrease in stored iron. The annual increments of estimated red blood cell
      (RBC) iron showed strong positive correlations with velocities in testicular
      volume and certainly in body height and weight. In contrast, the estimated
      changes in individual iron stores were not associated with any of those
      parameters. The lacking associations between iron stores and growth parameters
      are probably indicative of increasing intestinal absorption. Despite the
      relatively small quantitative role of iron stores in supplying iron for growth,
      falling iron stores probably play a more important regulatory role by stimulating
      iron absorption.

PMID- 9012684
TI  - Myeloid differentiation is impaired in transgenic mice with targeted expression
      of a dominant negative form of retinoid X receptor beta.
AB  - To investigate the in vivo function of retinoid X receptor (RXR) on myelopoiesis,
      We generated transgenic (Tg) mice with targeted expression of a dominant negative
      form of RXR beta in myeloid cells. In these Tg mice the transgene is expected to
      suppress the function of hetero dimeric receptors composed of RXR and its
      counterparts, such as retinoic acid receptor. Out of 12 mice analysed, one Tg
      mouse exhibited a severe maturation arrest at the promyelocytic stage. Three
      other Tg mice showed a mild inhibition of myeloid differentiation, which was
      further augmented when mice were treated with 5-fluorouracil (5-FU). Furthermore,
      four Tg mice showed impaired myeloid differentiation in response to the treatment
      by 5-FU on granulocyte-colony stimulating factor (G-CSF), although they exhibited
      apparently normal myelopoiesis in the untreated state. The phenotype of Tg mice
      observed after G-CSF treatment correlated with the expression level of the
      transgene, although the correlation was not found in untreated mice. These
      results indicated that myeloid differentiation is perturbed in the Tg mice by the
      dominant negative effect of the transgenic RXR, indicating that RXR plays a role
      in myelopoiesis.

PMID- 9012685
TI  - Functional activity of CD44 isoforms in haemopoiesis of the rat.
AB  - Expression of CD44 is involved in the maturation as well as the homing of
      haemopoietic progenitor cells. Whether these processes are mediated by CD44
      standard (CD44s) or variant (CD44v) isoforms is unknown. To assign functional
      activities of CD44 in haemopoiesis of the rat to distinct isoforms, ligand
      binding of haemopoietic progenitor cells was inhibited by monoclonal antibodies
      recognizing an epitope on CD44s (Ox50) or CD44 exon v6, (1.1ASML). The vast
      majority of rat bone marrow cells (BMC) as well as stromal cells and non-adherent
      cells in long-term bone marrown culture (LTBMC) expressed CD44s. Bone marrow
      cells and non-adherent cells in LTBMC, but not the stromal cells, also contained
      a population of large and granulated cells, which stained with anti-CD44v6. In
      vivo and in vitro reconstitution experiments revealed that homing of BMC as well
      as settlement on stromal elements was influenced exclusively by anti-CD44s, which
      also inhibited proliferation of progenitor cells. Anti-CD44v6 had no influence on
      homing and seeding, but interfered with stroma formation and progenitor
      maturation. Finally, restoration of functional activity of T-lineage cells was
      impaired in the presence of anti-CD44v6. The data indicate that CD44s and CD44v6
      fulfilled distinct functions in haemopoiesis of the rat. Although CD44s
      facilitated homing and expansion of stem cells, progenitor cells, CD44v6 was
      involved in differentiation processes, particularly of lymphoid progenitor cells.

PMID- 9012686
TI  - Ex vivo neutrophil function in response to three different doses of glycosylated
      rHuG-CSF (Lenograstim).
AB  - Granulocyte colony-stimulating factor (G-CSF) is being considered as adjuvant
      treatment for infections in non-neutropenic patients. Normal healthy donors were
      given rHuG-CSF (Lenograstim) at 2.5, 5.0 and 7.5 micrograms/kg subcutaneously
      daily for 5 d. Polymorphonuclear leucocyte (PMN) function tests were carried out
      on peripheral blood PMN before the first injection and at 24 h and 96 h.
      Circulating PMN levels were also measured at these time intervals and found to be
      significantly increased with all doses by 24 and 96 h. Investigation of cell
      surface antigen expression revealed no changes in beta 2 integrin (CD11b/ CD18)
      expression. L-selectin (CD62L) expression was reduced with all doses by 96 h,
      this being significant with the 7.5 micrograms/kg dose. Fc gamma RI (CD64) levels
      were significantly up-regulated with the 7.5 micrograms/kg dose by 96 h whereas
      Fc gamma RIII (CD16) expression was found to be reduced during G-CSF treatment.
      Superoxide anion production was significantly increased in response to N
      formylmethionyl-leucylphenylalanine (FMLP) and opsonized Staphylococcus
      epidermidis stimulation at 24 h and 96 h with the 5.0 and 7.5 micrograms/kg
      doses. The initial rate of phagocytosis (0-2 min) appeared to have increased with
      the 7.5 and 5.0 micrograms/kg doses at 96 and 24 h compared with PMN responses
      pretreatment, although these increases were not statistically significant. These
      results show that G-CSF enhances the functional responses of PMN stimulated by
      physiological agnonists and may help in the treatment of infections.

PMID- 9012687
TI  - Purified unfractionated G-CSF/chemotherapy mobilized CD34+ peripheral blood
      progenitors and not bone marrow CD34+ progenitors undergo selective erythroid
      differentiation in liquid culture in the presence of erythropoietin and stem cell
      factor.
AB  - A combination of erythropoietin (EPO) plus stem cell factor (SCF) drove purified
      unfractionated granulocyte colony stimulating factor (G-CSF)/chemotherapy
      mobilized peripheral blood CD34+ cells to selective erythroid differentiation in
      liquid culture with an average 28-fold increase in the total cell number after 21
      d. From day 6 of culture cytologic and cytofluorimetric characterization revealed
      that cultured cells belonged to the erythroid lineage with a gradual wave of
      maturation along the erythroid pathway to terminal cells. A similar pattern of
      erythroid differentiation was observed when the same peripheral blood CD34+ cells
      were culture with EPO plus SCF in serum-free medium. This cytokine combination
      produced selective erythroid differentiation with the complete exhaustion of the
      clonogenic potential on day 21. In parallel experiments the same circulating
      CD34+ cells underwent granulocytic/ monocytic differentiation in liquid culture
      in response to granulocyte-macrophage colony stimulating factor (GM-CSF),
      interleukin-3 (IL-3) and SCF, demonstrating that these CD34+ progenitors had
      intact pluripotent differentiating potential. Conversely, bone marrow CD34+ cells
      isolated from bone marrow allografts were unable to selectively differentiate
      along the erythroid pathway when they were exposed to EPO plus SCF combination.
      However, these cells maintained a greater number of colony forming cells on day
      21 of culture compared to mobilized peripheral blood CD34+ cells. This model is a
      simple and reliable way to obtain selective erythroid differentiation of
      peripheral blood G-CSF/ chemotherapy mobilized CD34+ progenitor cells in liquid
      culture. The absence of cytokines such as GM-CSF and IL-3 in the culture medium
      permits studies on in vitro erythropoiesis without disturbance of prevalent
      myelopoiesis.

PMID- 9012689
TI  - Novel band 3 variants (bands 3 Foggia, Napoli I and Napoli II) associated with
      hereditary spherocytosis and band 3 deficiency: status of the D38A polymorphism
      within the EPB3 locus.
AB  - We report three novel variants of band 3 associated with hereditary
      spherocytosis: band 3 Foggia (311delC; ACCCAC-->ACCAC), band 3 Napoli I (447insT;
      TCT-->TTCT) and band 3 Napoli II (1783N; ATC-->AAC). The first two mutations
      resulted in premature termination of translation, making one haploid set of band
      3 mRNA unavailable. Since it affected a highly conserved position at the terminal
      end of transmembrane domain 11, the third mutation prevented one haploid set of
      band 3 from becoming incorporated or stabilized into the membrane. These three
      mutations resulted in a reduction of the band 3 level in the red cell membrane
      (by 20-25%) and were dominantly transmitted. The D38A substitution (GAC-->GCC) is
      a low frequency change of band 3. In one compound heterozygote D38A/Napoli II, a
      markedly aggravated picture required early splenectomy. In contrast, the D38A
      change was not associated with deterioration in another compound heterozygote,
      carrying in trans, the previously recorded R760W mutation (CGG-->TGG). In the
      aggravated case, SSCP analysis did not exhibit any additional change in the two
      EPB3 alleles. Nor did it show any alteration in the exons of the two ANK1
      alleles, and the aggravating factor remained elusive. The D38A alteration should
      be regarded as an innocuous polymorphism.

PMID- 9012688
TI  - Generation of multinuclear tartrate-resistant acid phosphatase positive
      osteoclasts in liquid culture of purified human peripheral blood CD34+
      progenitors.
AB  - Circulating CD34+ cells were isolated from leukapheresis products collected from
      patients with ovarian cancer. CD34 contaminating cells, identified immediately
      after immunoselection, ranged from 5% to 25% in five different experiments and
      were predominantly CD3+ T-lymphocytes (range 2-12%), CD3+/CD16+/CD56+ natural
      killer cells (range 2-11%) and rare mature CD15+/ CD11b+ granulocytes (range 1
      2%). CD34+ cells were cultured in liquid medium in the presence of interleukin-3,
      granulocyte-macrophage colony stimulating factor. stem cell factor, granulocyte
      colony stimulating factor and a powerful proliferation with prevalent
      differentiation along the granulocytic/monocytic lineage was obtained. After 10 d
      of culture a small but consistent number of early multinucleated osteoclasts were
      identified with a frequency of one cell per 700 granulocytic/monocytic cells, as
      revealed by cytologic examination. This observation was confirmed by staining for
      tartrate-resistant acid phosphatase activity which revealed red multinucleated
      elements with a frequency comparable to that reported above. Conversely, no
      osteoclasts were observed in those cultures in which macrophage overgrowth was
      obtained by culturing CD34+ cells until day 35. These observations suggest that
      circulating progenitors have a multilineage potential in vitro and contribute to
      the clarification of osteoclast development in humans: additionally, they provide
      the basis for the future development of optimized osteoclast culture techniques
      in liquid medium and the basic culture system, to test the distinct activity of
      1,25(OH)2D3. parathyroid hormone interleukin-11 and of other cytokines on
      osteoclast development in humans.

PMID- 9012691
TI  - Mechanism of action of antithymocyte globulin in the treatment of aplastic
      anaemia: in vitro evidence for the presence of immunosuppressive mechanism.
AB  - Antithymocyte globulin (ATG) is one of the effective drugs used in the treatment
      of aplastic anaemia (AA). Although it has been speculated that the mechanism of
      action of ATG is mediated by its immunosuppressive effect on lymphocytes which
      might have an inhibitory effect on haemopoietic stem and progenitor cells, no
      definite evidence of the presence of such a mechanism has been demonstrated. In
      this study we investigated whether such a mechanism is truly operating in ATG
      therapy for AA. In five patients who responded to ATG, bone marrow cells were
      obtained after haematological recovery and CD34-positive cells were separated by
      immunobeads. Autologous CD34-positive cells were mixed with autologous peripheral
      CD4- or CD8-positive cells obtained before ATG therapy and after haematological
      recovery, liquid-cultured for 12h, and then cultured in methylcellulose for 14d
      in the presence of haemopoietic growth factors. In all five cases studied, only
      the CD8 cells obtained before ATG therapy suppressed the colony forming unit
      granulocyte-macrophage (CFU-GM)- and burst forming unit-erythroid (BFU-E)-derived
      colony formation. This result is definite evidence that one of the mechanisms of
      action of ATG in AA is an inhibitory effect on CD8-positive cells which have
      suppressive activity for the growth of haemopoietic progenitor cells.

PMID- 9012690
TI  - Splenic regrowth in sickle cell anaemia following hypertransfusion.
AB  - We describe five adult patients with sickle cell anaemia (SS) who developed
      clinical, radiological and histological evidence of splenic regrowth while
      receiving regular blood transfusions. Five patients, all homozygous SS, range 23
      34 years, were commenced on hypertransfusion therapy. Three patients were
      transfused because of severe recurrent vaso-occlusive crises, one for chronic
      sickle lung and one in an attempt to prevent deterioration of renal function. The
      mean duration of hypertransfusion prior to documentation of splenic regrowth was
      52 months (range 12-97 months). Two patients developed significant hypersplenism.
      One patient had clinically-apparent splenomegaly and four patients had
      splenomegaly documented on ultrasound. Splenic regrowth in hypertransfused adults
      with sickle cell anaemia is not infrequent and may have important clinical
      implications.

PMID- 9012692
TI  - Analysis of T-cell clonality in bone marrow of patients with acquired aplastic
      anaemia.
AB  - Acquired aplastic anaemia (AA) represents a state of bone marrow (BM) failure
      which is characterized by BM hypocellularity and pancytopenia. It has been
      hypothesized that in some AA patients, bone marrow failure is secondary to the
      targeted destruction of haemopoietic stem cells by autoreactive T cells. The
      response of T cells to antigenic stimulation has been shown, in a number of
      animal models and in autoimmune diseases, to result in the (oligo)clonal
      expansion of positively reacting T cells. For this reason, we studied the
      utilization of 24 T-cell receptor-variable gene segments (TCRBV) and the
      clonality in BM aspirates and peripheral blood (PB) of seven AA patients. BM from
      transplant donors served as controls. Determination of TCRBV gene segment usage
      revealed no significant differences between patients and controls. Clonality
      within each family was analysed by single-strand conformation polymorphism (SSCP)
      analysis. Clonal and clonally predominant bands were seen in BM of three AA
      patients in five to eight TCRBV families. Clonal rearrangements were encountered
      less often in BM of control subjects. In conclusion, our results suggest an
      antigen-driven T-cell response in the BM of predominantly AA patients resulting
      in oligoclonal T-cell outgrowth.

PMID- 9012693
TI  - Clinical characteristics predict response to antithymocyte globulin in paroxysmal
      nocturnal haemoglobinuria.
AB  - Seven patients with paroxysmal nocturnal haemoglobinuria (PNH) were treated with
      antithymocyte globulin (ATG). Each patient received ATG (20 mg/kg/d) for 8 d and
      prednisone to prevent or control serum sickness. Three patients experienced a
      sustained improvement in at least one peripheral blood cytopenia, including one
      patient who had a complete trilineage response. Several pretreatment clinical
      features appeared to be associated with response to ATG. All responding patients
      had hypoproliferative features including depressed platelet counts (< 30 x
      10(9)/l), and a minor degree of chronic haemolysis as indicated by relatively low
      reticulocyte counts (< 100 x 10(9)/l), lactate dehydrogenase (< 1000 U/l) and
      total bilirubin (< 17 mumol/l) levels. Responding patients continued to have
      chronic low-grade haemolysis after their response to immunosuppression that was
      similar to that observed prior to treatment. The non-responding patients had a
      classic haemolytic form of PNH characterized by elevated reticulocyte counts (>
      100 x 10(9)/l), lactate dehydrogenase (> 2000 U/l) and total bilirubin (> 17
      mumol/l) levels. The impaired haemopoiesis that occurs in hypoproliferative PNH
      may respond to ATG treatment, but the haemolytic component of the disease, and
      hence the PNH clone, is not altered by immunosuppressive therapy.

PMID- 9012694
TI  - Analysis of the p16INK4A, p15INK4B and p18INK4C genes in multiple myeloma.
AB  - To study the structural integrity of the cyclin-dependent kinase inhibitors known
      as INK4A (p16), INK4B (p15) and INK4C (p18) in multiple myeloma, we examined 20
      primary myeloma samples (including one case of plasma cell leukaemia) using
      polymerase chain reaction-single strand conformation polymorphism, and 17 samples
      were examined by Southern blot analysis. The plasma cell leukaemia sample had
      homozygous deletions of the p15 and p16 genes (6%). One myeloma case had a p15
      gene homozygous deletion (6%) with an intact p16 gene. This sample also had a p18
      homozygous deletion, suggesting that the deletion of both genes may be important
      in either the development or progression of myeloma. No point mutations of these
      INK4 genes were found in the 20 samples. This is the first report that indicates
      that deletions of p15, p16 and p18 genes occur in some individuals with multiple
      myeloma (2/17 cases).

PMID- 9012695
TI  - Serum markers of bone metabolism in multiple myeloma: prognostic value of the
      carboxy-terminal telopeptide of type I collagen (ICTP). Nordic Myeloma Study
      Group (NMSG).
AB  - This study was performed to evaluate the prognostic significance of serum markers
      of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide
      of type I collagen (ICTP) reflects degradation of bone, whereas serum
      osteocalcin, together with serum C-terminal propeptide of procollagen type I
      (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of
      bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum
      reflects synthesis of type III collagen. We analysed frozen sera from 109
      patients with newly diagnosed multiple myeloma. Serum ICTP was elevated (> 5.0
      micrograms/l) in most patients (median 6.6 micrograms/l range 1.4-29.4
      micrograms/l). Serum PIIINP was elevated (> 4.2 micrograms/l) in 46% (median 4.0
      micrograms/l, range 1.4-20.1 micrograms/l). Serum PICP was generally within the
      reference limits, whereas serum osteocalcin and serum bAP were elevated in 19%
      and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum beta 2
      microglobulin (beta 2m), serum calcium, performance status, and stage. In
      univariate analysis, the test variables serum ICTP (P = 0.026) and serum
      osteocalcin (P = 0.036) were found to be of prognostic value, but PIIINP, PICP,
      or bAP in serum were not. Serum ICTP and serum beta 2m had a similar prognostic
      value. In multivariate analysis, serum calcium showed the highest prognostic
      significance, and serum beta 2m was the only other variable of independent
      prognostic value. However, in normocalcaemic patients, serum ICTP showed the
      highest prognostic significance, followed by serum osteocalcin. Thus, the serum
      levels of ICTP and osteocalcin seem related to bone turnover and calcium
      metabolism, and provide further information about myeloma activity, particularly
      in normocalcaemic patients.

PMID- 9012696
TI  - Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia
      seen at a referral centre over a 16-year period.
AB  - To determine major presenting features of chronic myeloid leukaemia (CML) in
      current practice, we have reviewed the records of 430 patients with CML referred
      to the Hammersmith Hospital for allogeneic bone marrow transplantation since
      1981. Approximately 20% of cases were diagnosed incidentally. Symptoms such as
      fatigue and weight loss were associated with greater degrees of leucocytosis and
      splenomegaly and lower haemoglobin levels. Most bleeding patients had normal or
      elevated platelet counts, suggesting that platelet dysfunction was the primary
      cause of haemorrhage. Although thrombocytosis was common, thrombosis was not
      seen. Male patients and the relatively young presented with higher WBC counts and
      larger spleens. The reason that these groups were diagnosed with more advanced
      leukaemia is not clear. Although retrospective and limited to a select group of
      relatively young patients, this is the largest series to be reported on CML at
      diagnosis, and the first such report in modern clinical practice.

PMID- 9012697
TI  - Chronic eosinophilic leukaemia (CEL): a distinct myeloproliferative disease.
AB  - Chronic eosinophilic leukaemia has not yet been clearly defined, mainly due to
      the fact that it has not been conclusively shown as a monoclonal disease which
      should be separated from chronic myelogenous leukaemia, acute myelogenous
      leukaemia with eosinophilia (AML, FAB M4Eo), and the idiopathic hypereosinophilic
      syndrome. We report a patient with a white blood cell count of 17.6 x 10(9)/l
      with 74% eosinophils, normal platelet count and haemoglobin. No blasts were seen
      in the peripheral blood and the percentage of blasts in the bone marrow was < 3%.
      A diagnosis of chronic eosinophilic leukaemia was made. Chromosome analysis of a
      bone marrow aspirate disclosed a trisomy 15 together with loss of the Y
      chromosome. Moreover, FISH analysis on May-Grunwald-Giemsa-stained peripheral
      blood smears demonstrated trisomy 15 in the eosinophils. 3 months after initial
      diagnosis the patient went into blast crisis and died. The blast cells exhibited
      trisomy 15 and loss of the Y chromosome in a complex, aberrant karyotype. In
      conclusion, the case shows that chronic eosinophilic leukaemia is a monoclonal,
      myeloproliferative disease with eosinophils as part of the malignant clone.
      Clinically, chronic eosinophilic leukaemia can be separated into a chronic phase
      and a blast crisis.

PMID- 9012698
TI  - Ongoing immunoglobulin gene mutations in mantle cell lymphomas.
AB  - Mantle cell lymphomas (MCL) frequently show a vaguely follicular growth pattern.
      This phenomenon is thought to result from the colonization of reactive B-cell
      follicles by tumour cells. In view of the unique property of the germinal centre
      environment, antigen stimulation may play a role in the expansion of the tumour.
      To assess this, we have examined ongoing Ig mutations, which are genetic markers
      of B cells in persistent response to antigen stimulation, in five MCLs including
      two cases derived from the gastrointestinal tract known as lymphomatous polyposis
      (LP). We have specifically analysed Ig ongoing mutations in tumour cells from
      multiple lesions in one case and in tumour cells microdissected from colonized
      follicles in two cases. The consensus Ig VB sequences in four MCLs were
      identical, or almost identical (three cases 100%, one case 99% homology), to the
      published germlines, which in each case were those frequently employed by
      autoantibodies. The consensus Ig VH sequence in the remaining case displayed
      95.5% homology to the closest published germline. This may represent derivation
      from an unknown VH germline or a rare instance of somatic mutations. Extensive
      sequencing of the rearranged Ig genes revealed ongoing mutations within the
      tumour clone in two cases: one was a LP with multiple lesions of the
      gastrointestinal tract and the other was a nodal MCL in which tumour cells from
      colonized follicles were analysed. Our results indicate that MCLs are derived
      from pre-germinal centre B cells, possibly autoreactive B-cell clones. The
      ongoing mutations identified suggest a possible involvement of antigen
      stimulation in the clonal expansion of a proportion of MCLs.

PMID- 9012699
TI  - Follicular lymphoma immunoglobulin kappa light chains are affected by the antigen
      selection process, but to a lesser degree than their partner heavy chains.
AB  - Follicular lymphoma cells carry surface immunoglobulin whose heavy chain variable
      (VH) regions exhibit considerable divergence from the aminoacid sequence
      predicted by the germline nucleotide sequence as a result of the somatic
      hypermutation process. The present study examined the extent of somatic
      hypermutation in follicular lymphoma kappa light chain variable region (V kappa)
      genes about which the available data is limited. DNA extracted from fresh frozen
      lymph node tissue of 14 patients with follicular lymphoma at diagnosis was
      subjected to polymerase chain reaction (PCR) amplification aimed at detecting
      clonal VH and VL (L: light chain) gene rearrangements. Clonal V kappa gene
      rearrangements were detected in 10/14 cases. Amplified VH and V kappa genes of
      these 10 cases were directly sequenced by the dideoxy-chain termination method.
      In all cases, rearranged VH genes demonstrated numerous mutations clustering in
      the complementarity determining regions (CDRs), in keeping with previous reports.
      The degree of divergence of the rearranged V kappa genes from the closest
      homologous germline V kappa genes varied significantly. Furthermore, two patterns
      of mutations were observed: (i) in six cases (60%), mutations were most often of
      the replacement (R) type (changing the aminoacid sequence of the encoded
      polypeptide) in the CDRs and of the silent (S) type (leaving the aminoacid
      sequence of the encoded polypeptide unchanged) in the framework regions (FWRs)
      resulting in R:S ratios significantly greater than would have occurred by chance:
      (ii) in four cases (40%), very few or no mutations were observed and the
      distribution of mutations as well as the R:S mutation ratios did not differ
      significantly from what would have occurred by chance alone. These findings imply
      that, compared to their partner heavy chains, the kappa light chains of
      follicular lymphoma neoplastic B-cells' surface immunoglobulin (sIg): (i) are
      less affected by somatic hypermutation: (ii) play a less significant role in the
      antigen selection process.

PMID- 9012700
TI  - Fas/APO-1 (CD95)-mediated cytotoxicity is responsible for the apoptotic cell
      death of leukaemic cells induced by interleukin-2-activated T cells.
AB  - Apoptotic cell death is induced by the cross-linking of Fas/APO-1 receptor (CD95)
      in acute myelogenous leukaemia (AML) cells. Since CD95 ligand (CD95L) is
      expressed on interleukin-2 (IL-2)-activated T cells, we investigated the
      involvement of CD95-CD95L pathway in T cell-mediated cytotoxicity against AML
      cells. Activated CD8+ T cells could efficiently kill a parental CD95-sensitive
      AML cell line, MML-1 and, to a lesser extent, a CD95-resistant clone, MML-1R.
      Neither MML-1 nor MML-1R cells were killed by activated CD4+ T cells. The
      blocking monoclonal antibody (MoAb) against CD95, ZB4, caused a significant
      inhibition of T-cell-mediated cytotoxicity against MML-1 cells but not against
      MML-1R cells. Interestingly, MML-1 cells underwent the classic nuclear
      morphologic changes and DNA fragmentation characteristic of apoptosis when
      cultured with activated T cells. Enumeration of apoptotic and necrotic nuclei
      showed that both apoptosis and necrosis were induced in MML-1 cells, whereas
      necrosis was exclusively observed in MML-1R cells. Apoptosis of MML-1 cells was
      completely blocked in the presence of ZB4 MoAb. Similarly, blocking by ZB4 MoAb
      significantly inhibited T-cell-mediated lysis of fresh AML cells in a CD95
      sensitive group, but not in a CD95-refractory group. In addition CD8+ T cells
      expressed CD95L mRNA more abundantly than CD4+ T cells upon activation by IL-2.
      These findings suggest that T-cell-mediated cytotoxicity against AML cells
      requires participation of CD95-CD95L pathway for cytotoxic signal transduction
      leading to target apoptosis.

PMID- 9012701
TI  - Serum oncostatin M in multiple myeloma: association with prognostic factors.
AB  - The serum concentration of oncostatin M (OSM) was measured in 40 multiple myeloma
      patients at diagnosis. Serum OSM level exceeded the sensitivity limit of the
      ELISA assay in eight (20%) of these patients (OSM+ patients). The serum levels of
      IL-6, another member of the gp180 cytokine family and C-reactive protein (CRP) as
      a surrogate of IL-6 were significantly higher in OSM+ patients. There was a trend
      towards higher serum beta 2M concentration in OSM+ patients, whereas there was no
      difference in the serum sIL-6R level or clinical data (age, gender, myeloma
      protein or stage) between the two groups. Two human myeloma cell lines secreted
      OSM and IL-6, but not IL-11 or leukaemia inhibitory factor (LIF), which suggests
      an important role for OSM and IL-6 in supporting growth of myeloma cells.

PMID- 9012702
TI  - Allogeneic peripheral blood progenitor cell (PBPC) transplantation in children
      with haematological malignancies.
AB  - We report on five children with haematological malignancies who underwent
      allogeneic peripheral blood progenitor cell (PBPC) transplantation. PBPC were
      harvested from HLA-identical sibling donors after G-CSF (10 micrograms/kg/d s.c.)
      mobilization. Aphereses were carried out on day 5 after G-CSF using a Cobe
      Spectra blood cell separator. All PBPC allografts were cryopreserved before
      transplantation. The median of CD34+ cells and CD3+ cells infused were 14.1 x
      10(6)/kg recipient body weight (range 4.92-22.3) and 2.40 x 10(8)/kg recipient
      body weight (range 0.54 4.82), respectively. Engraftment occurred in all cases.
      The median time to a neutrophil count > 0.5 x 10(9)/l and a platelet count > 20 x
      10(9)/l were 15 and 14 d, respectively. The incidence of severe acute graft
      versus-host disease was 20%. These data suggest that allogeneic PBPC
      transplantation might be an alternative to bone marrow transplantation in
      children.

PMID- 9012703
TI  - PTHrP-mediated hypercalcaemia in a case of CML blast crisis.
AB  - We report a 52-year-old man with chronic myelogenous leukaemia (CML) who
      developed hypercalcaemia in blast crisis. There was a high serum level of
      parathyroid hormone-related protein (PTHrP). The leukaemia cells secreted PTHrP
      into culture medium when cultured in vitro and were shown to express PTHrP mRNA
      by reverse transcription-polymerase chain reaction. Transplantation of the
      leukaemia cells into nude mice resulted in the production of Ph1 chromosome
      positive tumours which caused increased levels of calcium and PTHrP in the blood.
      These results indicated that the hypercalcaemic event in the patient was induced
      by PTHrP of CML cell origin.

PMID- 9012704
TI  - Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study.
AB  - We examined the relationships of whole blood viscosity and its major determinants
      to incident cardiovascular events (ischaemic heart disease and stroke) in a
      prospective study of a random population sample of 1592 men and women aged 55-74
      years (the Edinburgh Artery Study). 272 fatal and non-fatal cardiovascular events
      occurred during 5 years of follow-up (cumulative incidence 17.1%). Age and sex
      adjusted mean levels of blood viscosity (3.70 v 3.55 mPa.s), haematocrit (46.2 v
      45.7%), haematocrit-corrected blood viscosity (3.57 v 3.48 mPa.s), plasma
      viscosity (1.35 v 1.33 mPa.s) and fibrinogen (2.88 v 2.67 g/l) were significantly
      higher in subjects who experienced events than in subjects who did not. The
      relationships of these rheological variables to cardiovascular events were at
      least as strong as those of conventional risk factors (smoking habit, diastolic
      blood pressure, and low-density lipoprotein cholesterol). After adjustment for
      these conventional risk factors, the associations of blood viscosity and
      haematocrit remained significant for stroke, but not for total events; whereas
      the associations of plasma viscosity and fibrinogen remained significant for
      total events and for stroke. These findings suggest that increased blood
      viscosity may be one plausible biological mechanism through which increases in
      haematocrit and fibrinogen may promote ischaemic heart disease and stroke.
      Randomized controlled trials of viscosity reduction in the prevention of
      cardiovascular events (e.g. by lowering high levels of haematocrit or plasma
      fibrinogen) are suggested.

PMID- 9012705
TI  - Evolution of blood coagulation and fibrinolysis parameters after abrupt versus
      gradual withdrawal of acenocoumarol in patients with venous thromboembolism: a
      double-blind randomized study.
AB  - A double-blind randomized trial was conducted to research a hypercoagulable state
      rebound after abrupt versus gradual withdrawal of acenocoumarol, 20 patients were
      included: 10 in the abrupt withdrawal group (AW) and 10 in the gradual withdrawal
      group (GW). Between days 1 and 15,F1 + 2 was higher in group AW (P < 0.002). A
      significant increase of D-dimer with time was found (P < 0.001) without
      difference between the two groups, tPA and PAI-1 levels remained stable
      throughout without difference between the two groups. No rebound phenomenon was
      observed. Four thrombotic recurrences were observed: group AW: 1, group GW: 3 (P
      = 0.29). There is neither clinical nor biological support for a gradual
      anticoagulation withdrawal.

PMID- 9012706
TI  - Acquired von Willebrand disease in a patient with angiodysplasia resulting from
      immune-mediated clearance of von Willebrand factor.
AB  - A patient with a severe bleeding tendency due to acquired von Willebrand disease
      (VWD) is presented. Although no underlying disorder has emerged during 6 years of
      follow-up, an immune-mediated mechanism was responsible for acquired VWD in this
      patient as demonstrated by detection of von Willebrand factor (VWF)/anti-VWF
      complexes in the patient's plasma and their removal by protein A-sepharose beads
      and resumption of normal haemostasis with correction of VWF antigen, VWF activity
      and VWF multimeric pattern after treatment of the patient with high-dose
      gammaglobulin. Detection of anti-VWF antibodies in the patient's plasma had a
      significant impact on the choice of therapeutic intervention to control bleeding.

PMID- 9012707
TI  - Efficient RT-PCR on platelet mRNA after long-term storage.
AB  - We have developed a procedure permitting RT-PCR from mRNA even after a long-term
      storage (1 year) of platelet samples in ethanol (EtOH-platelets) at -80 degrees
      C. To validate our method, we have analysed the human platelet alloantigen system
      (HPA-1) which is coded by beta 3 mRNA. We have also demonstrated the efficiency
      of amplification of part of the coding region for (i) alpha IIb subunit mRNA,
      (ii) alpha v subunit mRNA, and (iii) the seven transmembrane domain thrombin
      receptor mRNA.

PMID- 9012708
TI  - Transfer of anti-D antibodies across the isolated perfused human placental lobule
      and inhibition by high-dose intravenous immunoglobulin: a possible mechanism of
      action.
AB  - Using an in vitro perfusion model, therapeutic intravenous immunoglobulin (IVIgG)
      and IgG anti-D have been shown to cross the placenta from the maternal circuit to
      the fetal circuit. The transfer of all IgG species was linear with respect to
      time, and the amount of IgG transferred was proportional to the concentration of
      IgG in the maternal circuit ([IgG]m), but reached saturation at upper limits.
      With total [IgG]m at 6.5 g/l, 11.1 g/l or 26.2 g/l the increase in the fetal
      concentration of total IgG was 4.6 mg/l/h. 8.9 mg/l/h and 9.9 mg/l/h
      respectively. The rate of transfer of specific anti-D antibody to the fetal
      circuit was 0.026 IU/ml/h at a concentration of 38 IU/ml in the maternal circuit
      ([anti-D]m). High-dose therapeutic IVIgG added to the maternal circuit (total
      [IgG]m 29.2 g/l) significantly inhibited (P < 0.001) anti-D transfer to 0.004
      IU/ml/n. Addition of the same IVIgG at a lower concentration (total [IgG]m 11.1
      g/l) also reduced anti-D transfer, but only to 0.015 IU/l/h. The inhibitory
      effect of IVIgG does not appear to be mediated by anti-idiotypic or non-specific
      complexing with the anti-D, but may be the result of competition with IgG anti-D
      for placental Fc gamma receptors involved in the endocytotic uptake of IgG. The
      efficacy of IVIgG in this model suggests that it may be clinically useful in
      preventing HDN and other immune cytopenias, provided a sufficiently high dose is
      given.

PMID- 9012709
TI  - Cryoprecipitate prepared from plasma virally inactivated by the solvent detergent
      method.
AB  - There remains a small risk of viral transmission from single-donor blood
      components such as fresh frozen plasma (FFP) and cryoprecipitate which have not
      been subjected to a viral inactivation procedure. It is now possible to subject
      pooled FFP to viral inactivation by the solvent detergent (SD) treatment method,
      but with some loss of coagulation factors. To establish whether cryoprecipitate
      prepared from SD plasma would be suitable for the treatment of
      hypofibrinogenaemia and von Willebrand's disease (VWD), control and SD
      cryoprecipitate were assayed for factor VIII. von Willebrand factor (VWF) and
      fibrinogen content. In SD cryoprecipitate, levels of VWF activity and antigen
      were only 36% and 37% of control values respectively, whereas fibrinogen was 72%.
      The highest molecular weight multimer of VWF:Ag were absent from both SD plasma
      and SD cryoprecipitate. SD cryoprecipitate would thus be unsuitable for treating
      VWD, but would provide an alternative to untreated individual donor units of
      cryoprecipitate for the treatment of hypofibrinogenaemic states.

PMID- 9012710
TI  - Genetic typing of human platelet antigen 1 (HPA-1) by oligonucleotide ligation
      assay in a specific and reliable semi-automated system.
AB  - Genotyping of platelet alloantigens with the possibility of using any type of
      cellular material as a source of DNA has become a preferred procedure,
      particularly in thrombocytopenic patients when platelet counts are too low for
      phenotyping. Recently human platelet antigen 1 (HPA-1) has been identified as an
      inherited risk factor for coronary thrombosis. The different detection methods
      currently used have disadvantages for large-scale DNA diagnosis, including the
      need for electrophoresis (allele-specific restriction enzyme analysis,
      amplification with sequence-specific primers) or the potential risk of reduced
      specificity (allele-specific oligonucleotide hybridization). In this report we
      describe the adaptation of an automated oligonucleotide ligation assay to
      genotype HPA-1 in polymerase chain reaction (PCR)-amplified DNA samples. HPA-1a
      and HPA-1b phenotypes corresponded to the results of the different genotyping
      assays. The genotypes determined with the ELISA-based PCR-oligonucleotide
      ligation assay were in 100% concordance with the results obtained by conventional
      allele-specific restriction enzyme site analysis and PCR amplification with
      sequence-specific primers. The automated oligonucleotide ligation assay provides
      a rapid, reliable, nonisotopic method to genotype human platelet antigens that
      can rapidly be applied to large population screening.

PMID- 9012711
TI  - Comparison of the direct platelet immunofluorescence test (direct PIFT) with a
      modified direct monoclonal antibody-specific immobilization of platelet antigens
      (direct MAIPA) in detection of platelet-associated IgG.
AB  - Glycoprotein (GP)-specific platelet-associated IgG (PA-IgG) may be demonstrable
      in autoimmune-mediated thrombocytopenia. We studied 159 consecutive patients with
      histories of thrombocytopenia by a modified direct monoclonal antibody-specific
      immobilization of platelet antigens (direct MAIPA) assay, which immobilizes GP
      IIb/ IIIa, GP Ib/IX and GP Ia/IIa simultaneously. This modification requires
      smaller quantities of platelets than standard measurements performed separately.
      PA-IgG was present in 84/159 (53%) patients, as shown by the direct platelet
      immunofluorescence test (PIFT) with flow cytometry as a reference. PA-IgG against
      GP IIb/IIIa and/or GP Ib/IX and/or GP Ia/IIa was noted in 46 patients (29%), of
      whom 93% (43/46)-were also PA-IgG positive. The amount of PA-IgG detected by PIFT
      correlated directly with that detected by direct MAIPA (r = 0.71; P < 0.001).
      Only three patients 12548 with negative direct PIFT had GP-specific PA-IgG. GPV
      specific PA-IgG was detected in 13 (10%) of the 125 patients, in whom further
      studies could be performed. In the subgroup of patients with GP-specific PA-IgG,
      the median fluorescence intensities of direct PIFT were higher than in patients
      with no GP-specific PA-IgG (P < 0.001). Direct PIFT and direct MAIPA divided the
      patients into asymmetric subgroups. However, the relative roles of these tests in
      the diagnosis of autoimmune-mediated thrombocytopenia await further studies.

PMID- 9012712
TI  - t(4;12)(q11;p13) in a CD7-negative acute myeloid leukaemia.

PMID- 9012713
TI  - Therapy of chronic autoimmune purpura (ITP)

PMID- 9012714
TI  - Those MCC examination blues.

PMID- 9012715
TI  - Canadian infant mortality: 1994 update.

PMID- 9012716
TI  - Beware the curriculum-reform troops.

PMID- 9012717
TI  - Spirometry utilization in Ontario: practice patterns and policy implications.
AB  - OBJECTIVE: To describe growth and regional variation in the use of spirometry
      (flow studies) in Ontario. DESIGN: Retrospective analysis of Ontario Health
      Insurance Plan (OHIP) fee-for-service billing data for spirometry from the 1989
      90 to 1994-95 fiscal years. SETTING: Physicians' office practices in Ontario.
      OUTCOME MEASURES: Number of flow studies and associated expenditures, number and
      specialty of physicians performing flow studies and the distribution of their
      billings, number of studies per capita by age group of patients, expenditures by
      region and measures of variation among regions. RESULTS: In 1994-95, $14.13
      million was spent on flow studies in Ontario. This expenditure increased by 36.9%
      from 1989-90 to 1994-95, exceeding the overall growth rate of 20.8% for all
      expenditures under OHIP. Expenditure growth was driven by an increase in the
      number of physicians performing spirometry rather than a higher volume of
      services performed per physician. The substitution of flow-volume loops, for
      which the fee is higher, for simple spirograms also contributed to expenditure
      growth. There were wide regional variations in spirometry utilization. A small
      number of general practitioners and family physicians accounted for much of the
      regional variation. CONCLUSIONS: The rapid growth in spirometry utilization may
      stem from the diffusion of inexpensive spirometers in physicians' offices and
      from increased awareness of guidelines promoting the use of flow measurements.
      However, the wide regional variation in utilization may indicate either
      incomplete implementation of spirometry guidelines or lack of direction on the
      appropriate frequency of spirometry use. Clearer, evidence-based guidelines and
      an implementation strategy are needed. Also required is further study of possible
      inadequate access to spirometry in low-use regions and inappropriate use in high
      use regions, where spirometry use is concentrated among a small number of
      physicians.

PMID- 9012718
TI  - Deciding about mechanical ventilation in end-stage chronic obstructive pulmonary
      disease: how respirologists perceive their role.
AB  - OBJECTIVE: To determine when respirologists approach patients with end-stage
      chronic obstructive pulmonary disease (COPD) to decide about the use of
      mechanical ventilation, what information they provide to patients and how they
      provide it. DESIGN: Self-administered national survey. PARTICIPANTS: All Canadian
      specialists in respiratory medicine; of 401 eligible respirologists, 279 (69.6%)
      returned a completed questionnaire. OUTCOME MEASURES: Timing and content of
      doctor-patient discussions regarding mechanical ventilation; physicians'
      perception of their level of involvement in the decision-making process; and
      patient and physician characteristics that may influence decisions. RESULTS:
      Discussions were reported to occur most often at advanced stages of COPD: when
      the patient's dyspnea was severe (reported by 235 [84.2%] of the respondents) or
      when the patient's forced expiratory volume in the first second was 30% or less
      than predicted value (reported by 210 [75.3%]). A total of 120 respondents
      (43.0%) stated that they discuss mechanical ventilation with 40% or less of their
      COPD patients before an exacerbation necessitates ventilatory support. Most (154
      [55.2%]) described the decision-making process as a collaboration between patient
      and physician; 83 (29.7%) reported that the patient decides after he or she has
      considered the physician's opinion. Over half (148 [53.0%]) of the respondents
      indicated that they occasionally, often or always modify the information provided
      to patients in order to influence their decision about mechanical ventilation.
      CONCLUSIONS: Discussions with COPD patients concerning end-of-life decisions
      about mechanical ventilation are reported to occur in advanced stages of the
      disease or not at all, with patients' input where possible. Information presented
      to patients is often modified in order to influence the decision. Future studies
      should explore ways to involve patients further in the decision-making process
      and to improve the process for both patients and physicians.

PMID- 9012719
TI  - The effect of tobacco tax cuts on cigarette smoking in Canada.
AB  - OBJECTIVE: To assess the effect of the tobacco tax cuts made in 1994 on the
      smoking habits of Canadians. DESIGN: Population-based retrospective cohort study.
      DATA: Data from the Survey on Smoking in Canada conducted by Statistics Canada on
      11,119 respondents 15 years of age and older, who were interviewed about their
      smoking habits on 4 occasions, approximately every 3 months from January 1994 to
      February 1995. OUTCOME MEASURES: Changes in smoking prevalence, incidence, quit
      rates and mean number of cigarettes smoked per day in the provinces where tobacco
      taxes were cut and in those where taxes were not cut. RESULTS: During the survey,
      smoking prevalence decreased in all provinces, whether or not cigarette taxes had
      been cut. However, the prevalence of smoking was greater in the provinces where
      tobacco taxes had been cut than in those where they had not, and this difference
      increased from 2.0% at the beginning of the survey to 3.4% by the end (p <
      0.001). In addition, rates of starting cigarette smoking were higher and smoking
      quit rates were lower in the provinces where taxes had been cut than in those
      where taxes had not been cut. CONCLUSION: Although smoking rates are declining in
      Canada, tobacco tax cuts appear to have slowed the rate of decline by inducing
      more nonsmokers to take up smoking and leading fewer smokers to quit.

PMID- 9012720
TI  - Randomization in the Canadian National Breast Screening Study: a review for
      evidence of subversion.
AB  - The authors assess the randomization strategy that had been used in the Canadian
      National Breast Screening Study (NBSS). Document experts at a private
      investigation and security company were hired to assist in reviewing instances in
      which names of subjects were altered in the "allocation books" (the basic
      instrument used to assign, at random, participants to either the mammography or
      the usual-care arm). The review was restricted to records from 3 NBSS centres
      where women assigned to the mammography arm had a distinctly higher (not
      necessarily significant) number of deaths from breast cancer than those assigned
      to the usual-care arm, and to records from 2 centres where, for limited periods,
      administrative problems were reported. In most cases the underlying, original
      name could be identified. The document experts found no evidence of a deliberate
      attempt to conceal the alterations. A search of the NBSS database for the
      underlying and superimposed names revealed that only 1 of the women whose name
      had been deleted or superimpsed died of breast cancer. She was in the mammography
      arm. The authors' thorough review of ways in which the randomization could have
      been subverted failed to uncover credible evidence of it. They conclude that even
      if there had been acts of subversion, they could only have been few in number
      and, given that there was only 1 death from breast cancer in the group reviewed,
      the alterations could have had only a trivial effect on the study findings as
      reported in 1992.

PMID- 9012721
TI  - Spirometric testing: how much is enough?
AB  - The author comments on the report by Dr. Benjamin Chan and associates on
      spirometry utilization rates in Ontario (see pages 169 to 176 of this issue).
      Their findings indicate that the overall utilization of spirometry in the
      province is not unreasonably high and may in fact be too low in certain regions
      and patient groups. The author argues, however, that to a large extent the wrong
      type of spirometry is being done. Although the wider use of flow studies should
      be promoted, the utility of flow-volume loops rather than simple spirograms as an
      office procedure is highly questionable.

PMID- 9012722
TI  - Taxes and the tobacco wars.
AB  - In this issue (see pages 187 to 191) Dr. Vivian H. Hamilton and associates
      demonstrate that tax reductions introduced in 5 Canadian provinces in 1994 slowed
      the rate of decline in cigarette consumption in those jurisdictions. Although
      both reductions and increases in taxation have been shown to influence tobacco
      consumption, changes in smoking habits must also be understood in the context of
      battles being waged on other fronts in the tobacco wars. In addition, more finely
      detailed analyses are needed to determine the impact of taxation and other
      factors on the smoking habits of specific subgroups of the population,
      particularly teenagers.

PMID- 9012723
TI  - The review of randomization in the Canadian National Breast Screening Study. Is
      the debate over?
AB  - The randomization procedure in the Canadian National Breast Screening Study
      (NBSS) is assessed in this issue (see pages 193 to 199) by Drs. John C. Bailar
      III and Brian MacMahon. They conclude that although there was ample opportunity
      for the randomization process to be subverted, no evidence of subversion was
      found. This is unlikely to allay all concerns about randomization, because there
      are still puzzling differences between the arms of the NBSS in a number of
      baseline variables. For example, the existence of prior health claims for breast
      cancer for women who entered the NBSS in Manitoba has raised the possibility that
      subversion occurred. Although the question may never be resolved, one lesion is
      clear: randomization in clinical trials should be managed in a manner that makes
      subversion impossible. As for the clinical implications of the NBSS for women in
      their 40s, physicians may now look to the results of randomized trials that have
      been published more recently. A meta-analysis of these results suggests that
      screening mammography reduces deaths from breast cancer among women in their 40s,
      but continued follow-up over the next few years will be needed to settle the
      debate.

PMID- 9012724
TI  - The review of randomization in the Canadian National Breast Screening Study. What
      does the verdict mean for clinicians?
AB  - What is the practising clinician to make of the review by Drs. John C. Bailar III
      and Brian MacMahon (see pages 193 to 199 of this issue) of the randomization
      procedure used in the Canadian National Breast Screening Study? Their conclusion
      that any flaws in randomization would not have affected the published data is
      reassuring. Nevertheless, the review has not resolved the controversy surrounding
      the recommendations for screening mammography for women aged 40-49.
      Recommendations must be based on strong evidence that the benefits of population
      based testing outweigh the harms. The absence of such evidence for women aged 40
      49 should not, however, preclude the use of mammography as a diagnostic test for
      women in their 40s whose clinical signs require follow-up. Mammography could also
      be considered for women whose family history or other factors suggest an
      increased risk for breast cancer, provided that the limitations and potential
      disadvantages of testing are explained.

PMID- 9012725
TI  - Teaching medical students to lie. The disturbing contradiction: medical ideals
      and the resident-selection process.
AB  - Although truthfulness and honesty have long been considered fundamental values
      within the medical profession, lying and deception have become standard practices
      within medicine's resident-selection process. Dishonesty is incorporated into and
      encouraged during this process, and there is little need for medical students and
      other participants to reflect upon their actions. This essay, which won the $1500
      first prize in CMAJs 1996 Logie Medical Ethics Essay Contest, looks at the
      serious consequences of this lying and deception. Dr. Tara Young discusses the
      moral dilemma applicants for residencies face during their final year of
      undergraduate training.

PMID- 9012726
TI  - Bioethics for clinicians: 7. Truth telling.
AB  - The standard of professional candour with patients has undergone a significant
      change over the past 30 years. Independent of their obligation to disclose
      information necessary for informed consent, physicians are increasingly expected
      to communicate important information to patients that is not immediately related
      to treatment decisions. The purpose of truth telling is not simply to enable
      patients to make informed choices about health care and other aspects of their
      lives but also to inform them about their situation. Truth telling fosters trust
      in the medical profession and rests on the respect owed to patients as persons.
      It also prevents harm, as patients who are uninformed about their situation may
      fail to get medical help when they should.

PMID- 9012727
TI  - Learning from Amy. A remarkable patient provokes anguished debate about
      rationality, autonomy and the right to die.

PMID- 9012728
TI  - HIV postexposure prophylaxis: new recommendations.

PMID- 9012729
TI  - Tobacco wars. The bloody battle between good health and good politics.
AB  - A battle to introduce new antitobacco legislation in Canada has caused political
      battles within the Liberal Party. While one side is worried about the need to
      protect people's health, another is worried about the potential loss of jobs
      within the tobacco industry--many of which are located in politically volatile
      Quebec. Charlotte Gray writes about the machinations that led to the introduction
      of new smoking legislation in the House of Commons in November.

PMID- 9012730
TI  - Tobacco and health.

PMID- 9012731
TI  - Right to bill may affect amount of tobacco counselling by MDs.
AB  - Unpublished data from Health Canada indicate that only 32% of Canada's family
      physicians believe they can bill their health plans for providing smoking
      cessation counselling to patients with no smoking-related illness. A CMA study of
      provincial billing codes determined that all provinces and territories except
      British Columbia and Alberta have billing codes for clinical tobacco
      interventions, which include counselling. Ontario leads the way with 4 separate
      codes.

PMID- 9012732
TI  - Canada a country of two solitudes when smoking rates among anglophones,
      francophones compared.
AB  - Delegates attending a recent national conference on smoking and health learned
      that there are distinct differences in smoking habits between anglophones and
      francophones, and that Quebec has the world's highest smoking rate for adult
      women. Speakers said the high smoking rate in Quebec points to the need for
      francophone-specific antismoking messages, not simply messages that have been
      translated from English.

PMID- 9012733
TI  - Kit helps physicians, women work together to weigh HRT risks, benefits.
AB  - The Ottawa Health Decision Centre is developing a line of decision AIDS to make
      it easier for physicians to discuss potential therapies with patients. The first
      kit, Making choices: hormones after menopause, helps women weigh the risks and
      benefits of hormone replacement therapy.

PMID- 9012734
TI  - Fraud worries insurance companies but should concern physicians too, industry
      says.
AB  - The amount of insurance fraud is increasing in Canada. This should worry
      physicians, because all personal-injury claims must be substantiated by a medical
      certificate. The vast majority of physicians are honest and ethical, fraud
      investigators say, but some are being duped as patients scheme to cheat the
      insurance industry. In one sensational auto-insurance-fraud case, some Ontario
      physicians are being investigated about possible involvement in a self-referral
      scheme. Nicole Baer looks at insurance fraud and the challenges it poses for
      doctors.

PMID- 9012735
TI  - Is informed consent possible in the rapidly evolving world of DNA sampling?
AB  - Ethical concerns about the human genome diversity project were discussed in
      Montreal last year during the 1st International Conference on DNA Sampling and
      Banking. This, the first article in a 2-part series on the conference, examines
      issues related to informed consent.

PMID- 9012736
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Medical Journal Editors.

PMID- 9012737
TI  - Inhibition of stimulus-induced endothelial cell intercellular adhesion molecule
      1, E-selectin, and vascular cellular adhesion molecule-1 expression by
      arachidonic acid and its hydroxy and hydroperoxy derivatives.
AB  - Localized adhesion of peripheral blood leukocytes to the endothelial lining is
      essential for their exit from the blood under both physiological and pathological
      conditions. The establishment, development, and resolution of the inflammatory
      response is regulated by an array of mediators, many of which remain to be
      categorized. These include arachidonic acid (20:4n-6) and its hydroperoxy (HPETE)
      and hydroxy (HETE) derivatives, which are released during inflammation. The data
      show that human umbilical vein endothelial cells, pretreated with these fatty
      acids, have a reduced ability to be stimulated by tumor necrosis factor-alpha
      (TNF-alpha) for enhanced neutrophil and monocyte adhesion; the order of
      inhibitory activity being 15-HPETE > 15-HETE > 20:4 (n-6). This fatty acid
      induced inhibitory activity was reflected in the ability of the mediators to
      decrease the TNF-alpha-induced expression of the following endothelial adhesion
      molecules: intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular
      cell adhesion molecule-1 (VCAM-1), measured by both enzyme-linked immunosorbent
      assay and flow cytometric analysis. TNF-alpha-induced increased expression of
      ICAM-1, E-selectin, and VCAM-1 mRNA was significantly depressed by 15-HPETE.
      Constitutively expressed ICAM-1 and ICAM-1 mRNAs were unchanged by the fatty
      acids. The saturated fatty acid 20:0 and the methyl ester of 20:4(n-6) had no
      inhibitory activity. The binding of TNF-alpha to its receptors was not altered by
      these fatty acids. The fatty acids also inhibited the expression of ICAM-1 and E
      selectin induced by phorbol 12-myristate 13-acetate, showing that inhibition
      occurred at a post-TNF-alpha receptor binding level. The 15-HPETE was found to
      inhibit the TNF-alpha-induced increase in adhesion molecule expression in the
      early stage of the incubation, but expression returned to normal after 18 hours.
      An effect of 15-HPETE on the early cell signaling system was demonstrated by the
      ability of this fatty acid to inhibit agonist-induced protein kinase C
      translocation.

PMID- 9012738
TI  - The integrin very late antigen-4 is expressed in human smooth muscle cell.
      Involvement of alpha 4 and vascular cell adhesion molecule-1 during smooth muscle
      cell differentiation.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) and its counterreceptor, the integrin
      very late antigen-4 (VLA-4), have recently been identified in smooth muscle cells
      during intimal thickening in humans and in newly forming vessels during ontogeny
      in mice, respectively. We examined the coexpression of VCAM-1 and the alpha 4
      integrin subunit in human smooth muscle cells. The expression of VCAM-1 and alpha
      4 subunit were studied during development of the aorta. In the 10-week-old human
      fetal aorta, VCAM-1 and alpha 4 were strongly expressed in smooth muscle cells.
      Their expression was dramatically reduced within the 24th week of gestation and
      disappeared in the adult aortic media. However, smooth muscle cells from intimal
      atherosclerotic thickening of adult aorta reexpressed both VCAM-1 and alpha 4. In
      a culture model mimicking smooth muscle differentiation, VCAM-1 mRNA and protein
      and alpha 4 integrin protein were coexpressed with smooth muscle-specific
      variants of cytoskeletal and contractile proteins, smooth muscle myosin heavy
      chain, caldesmon heavy chain, and desmin. Treatment with antibodies against VCAM
      1 or alpha 4 integrin subunit interfered with the mRNA induction of smooth muscle
      specific markers of differentiation. These results in vitro, associated with the
      transitory expression of VCAM-1 and VLA-4 during vascular ontogeny and the
      atherosclerosis process, point to a possible role of VCAM-1 and VLA-4 in the
      induction of smooth muscle differentiation.

PMID- 9012739
TI  - Electrophysiological consequences of purinergic receptor stimulation in isolated
      rat pulmonary arterial myocytes.
AB  - Neither the electrophysiological effects of purinergic receptor stimulation nor
      the role of ATP in regulating the tone of pulmonary arterial smooth muscle has
      been determined. Therefore, we investigated the effects of purine nucleotides on
      acutely dissociated smooth muscle cells from rat small pulmonary arteries using
      the patch-clamp recording technique. Extracellular application of ATP activated a
      fast transient inward current (which decayed in the continued presence of the
      nucleotide) and produced sustained periodic oscillations of predominantly inward
      current. Pharmacological and anion substitution experiments revealed that the
      transient inward current was carried by the movement of cations. In contrast, the
      periodic oscillations of current were due primarily to a Ca(2+)-activated Cl-
      current (ICl,Ca) dependent on the release of Ca2+ from intracellular stores.
      Experiments using ATP analogues revealed the following order of potency for
      activation of the fast transient inward current: 2-methylthio ATP (2-meSATP) >
      ATP > alpha,beta-methylene ATP (alpha,beta-meATP) > > ADP > UTP = adenosine.
      Cross desensitization was seen between applications of ATP, alpha,beta-meATP, and
      2-meSATP, suggesting that these agonists act via a common site. The order of
      potency for activation of ICl,Ca was UTP = ATP > > ADP > or = 2-meSATP >
      alpha,beta-meATP = adenosine. Both the fast transient inward current and ICl,Ca
      evoked by ATP and its analogues were abolished by the nonselective P2
      purinoceptor antagonist suramin. These results show the existence of P2x and P2U
      purinoceptor subtypes in pulmonary arterial smooth muscle cells. Stimulation of
      these receptors results in activation of a fast transient inward cation current
      and ICl,Ca, respectively. It is likely that ATP acts via these receptor subtypes
      to regulate pulmonary arterial tone under physiological or pathological
      conditions.

PMID- 9012740
TI  - Role of Ca2+ in metabolic inhibition-induced norepinephrine release in rat brain
      synaptosomes.
AB  - Ischemia and simulated ischemic conditions induce enhanced release of
      norepinephrine (NE) in the brain and the heart. Although studies with neuronal
      preparations demonstrated a rise in [Ca2+]i under energy-depleted conditions,
      such release of NE in the heart appears to be predominantly Ca2+ independent.
      Since Ca2+ overload occurs in ischemia or energy depletion and since a rise in
      [Ca2+]i triggers exocytosis without membrane depolarization, we tested the
      possibility, using brain synaptosomes, that increased NE release could be, at
      least in part, a consequence of raised [Ca2+]i. Brain synaptosomes were incubated
      with Krebs-Henseleit medium, and ischemia was mimicked by treatment with
      metabolic inhibitors. NE content in incubation medium (supernatant) and
      synaptosomes was analyzed chromatographically. Treatment with metabolic
      inhibitors reduced ATP content by 75% and increased [Ca2+]i by more than fourfold
      within minutes. Metabolic inhibition elicited NE release, which started within 10
      minutes and reached a maximum after 30 minutes, with a corresponding 55%
      reduction in synaptosomal NE content after 40 minutes. NE release, together with
      a marked increase in [Ca2+]i, was also induced in energy-depleted synaptosomes by
      Ca2+ repletion after incubation with the Ca(2+)-free medium. Effects on NE
      release of various interventions to prevent Ca2+ overload were tested. Omission
      of Ca2+ from the incubation medium or loading synaptosomes with the Ca2+ chelator
      BAPTA-AM (20 and 100 mumol/L) prevented NE release, indicating a Ca(2+)-dependent
      mechanism. Inhibition of Ca2+ channels with omega-conotoxin, cadmium, or
      nifedipine had no effect on NE release during energy depletion. In contrast,
      nickel and 3,4-dichlorobenzamil, Na(+)-Ca2+ exchange inhibitors, dose-dependently
      inhibited NE release. In conclusion, this study provides evidence that under
      energy-depleted conditions, Ca2+ overload in synaptosomes of noradrenergic
      neurons from the brain is an important mechanism for the enhanced release of NE
      and that a reversal of Na(+)-Ca2+ exchange may be the key pathway leading to
      intraneuronal Ca2+ overload.

PMID- 9012741
TI  - In vitro modulation of a resistance artery diameter by the tissue renin
      angiotensin system of a large donor artery.
AB  - A local renin-angiotensin system (RAS) is present in the vasculature and might
      have an important role in the control of vascular resistance. In order to assess
      its functional role in the control of vasomotor tone, we investigated the effect
      of the RAS of a donor vessel (rat carotid artery) on the diameter of a recipient
      rat mesenteric resistance artery. Arteries were perfused in series in an
      arteriograph at a rate of 100 microL/min, under a pressure of 100 mm Hg. The two
      vessels were superfused in separate organ chambers to which drugs were added.
      Recipient artery internal diameter was measured continuously. Phenylephrine (0.1
      mumol/L) was present in the organ baths throughout the experiments, ensuring a
      preconstriction of the recipient artery (236 +/- 4 to 174 +/- 3 microns, n = 65
      arterial segments from 34 rats). The angiotensin I-converting enzyme inhibitors
      (ACEIs) cilazapril (1 mumol/L) and captopril (10 mumol/L) inhibited phenylephrine
      induced constriction by 30 +/- 12% (n = 7, P < .001) and 20 +/- 8% (n = 5, P <
      .01), respectively. Addition of cilazapril (1 mumol/L) or captopril (10 mumol/L)
      to the donor vessel chamber further inhibited the constriction by 8 +/- 3% (n =
      7, P < .01) and 31 +/- 10% (n = 5, P < .05), respectively. The angiotensin II
      receptor (AT1) antagonist losartan (10 mumol/L) prevented, in part, the
      relaxation due to the ACEI. The association of losartan (10 mumol/L) with the
      bradykinin B2 receptor antagonist HOE 140 (1 mumol/L) totally prevented the
      relaxation due to the ACEI. Finally, angiotensin II was measured in the perfusate
      of the carotid artery and was found to be released at a rate of 11.9 +/- 2.2 pg
      in 60 minutes (n = 8), which was significantly decreased to 1.4 +/- 0.4 pg in 60
      minutes (n = 4) by cilazapril (1 mumol/L). This study provides functional
      evidence that tissue-generated angiotensin II and bradykinin, produced locally
      and in upstream arteries, control the diameter of a resistance mesenteric artery.

PMID- 9012742
TI  - Endogenous nitric oxide masks alpha 2-adrenergic coronary vasoconstriction during
      exercise in the ischemic heart.
AB  - Previously, we observed that alpha 1-but not alpha 2-adrenergic vasoconstriction
      restricted blood flow distal to a coronary artery stenosis that resulted in
      myocardial hypoperfusion during exercise. This study was performed to test the
      hypothesis that vascular smooth muscle alpha 2-adrenergic vasoconstriction during
      exercise does exert a flow-limiting effect distal to a coronary artery stenosis
      but that this action is counterbalanced by simultaneous endothelial alpha 2
      adrenergic stimulation of NO production. Eight dogs instrumented with a Doppler
      velocity probe, hydraulic occluder, and indwelling microcatheter in the left
      anterior descending coronary artery (LAD) were studied during treadmill exercise
      in the presence of a coronary artery stenosis before and during infusion of the
      alpha 2-adrenergic receptor antagonist idazoxan (1.0 microgram.kg-1.min-1 IC)
      before and after NO synthase blockade with NG-monomethyl-L-arginine (LNNA, 1.5
      mg/kg IC). Coronary pressure distal to the stenosis was maintained constant
      during the control period and after administration of idazoxan before and after
      LNNA. Neither idazoxan nor LNNA altered any of the systemic hemodynamic variables
      either at rest or during exercise. During exercise in the absence of a stenosis,
      idazoxan and LNNA had no effect on coronary blood flow. In the presence of a
      stenosis that decreased distal coronary pressure to 52 +/- 3 mm Hg, mean
      myocardial blood flow measured with microspheres was 0.87 +/- 0.17 mL.min-1.g-1
      in the LAD-dependent region and 2.52 +/- 0.30 mL.min-1.g-1 in the posterior
      control region, respectively. With no change in distal coronary pressure,
      idazoxan had no effect on mean myocardial blood flow in the LAD region (0.86 +/-
      0.17 mL.min-1.g-1), but LNNA decreased mean myocardial blood flow to 0.49 +/-
      0.09 (P < .01). However, when idazoxan was infused during exercise in the
      presence of a coronary artery stenosis after LNNA administration, idazoxan
      increased mean myocardial blood flow to 0.62 +/- 0.13 mL.min-1.g-1 (P < .01).
      These data demonstrate that alpha 2-adrenergic stimulation of endothelial NO
      production, which occurs during exercise in the presence of a flow-limiting
      coronary artery stenosis, acts to counterbalance vascular smooth muscle alpha 2
      adrenergic vasoconstriction.

PMID- 9012743
TI  - Residence time of low-density lipoprotein in the normal and atherosclerotic
      rabbit aorta.
AB  - Previous results from this laboratory found that the arterial low-density
      lipoprotein (LDL) residence time in lesion-prone aortic sites was longer in
      hyperlipidemic rabbits before lesion formation than in the corresponding sites in
      normolipidemic rabbits. The calculation of residence time in the previous study
      assumed that the arterial wall was homogeneous; the present study reexamines the
      issue using a method that does not require such an assumption. The concentration
      of radiolabeled arterial LDL was measured in New Zealand White rabbits killed at
      several different times (0.5 to 72 hours) after injection of labeled LDL. Using a
      stochastic analysis, arterial LDL residence time was calculated from the pooled
      labeled arterial LDL measurements from these rabbits. In these studies, the
      arterial LDL residence times in normolipidemic and hyperlipidemic rabbits before
      lesion formation were similar in both the lesion-prone and -resistant sites.
      However, immediately upon development of early fatty streak lesions, the arterial
      LDL residence time increased dramatically. After only 16 days of cholesterol
      feeding, the residence time was 10 times longer in the lesioned aortic arch
      compared with similar tissue from normolipidemic rabbits (4 to 45 hours). After
      21 days of cholesterol feeding, the residence time of LDL in the lesioned aortic
      arch increased to > 25-fold that of normolipidemic tissue. Similar results were
      observed in the lesioned tissue of the abdominal branchings. This early retention
      of LDL suggests that significant changes are taking place within the arterial
      wall during this critical stage of early lesion development.

PMID- 9012744
TI  - Functional and biochemical analysis of angiotensin II-forming pathways in the
      human heart.
AB  - Blockade of the renin-angiotensin system by inhibition of angiotensin-converting
      enzyme (ACE) is beneficial for the treatment of hypertension and congestive heart
      failure. However, it is unclear how complete the blockade by ACE inhibitors is
      and if there is continuing angiotensin II (Ang II) formation during chronic
      treatment with ACE inhibitors. Indeed chymase, a serine protease, which is able
      to form angiotensin II from angiotensin I (Ang I) and cannot be blocked by ACE
      inhibitors, has been shown to be present in human heart. The goal of the present
      study was to evaluate the extent of renin-angiotensin system blockade and the Ang
      II-forming pathways in cardiac tissue of patients chronically treated with ACE
      inhibitors or in patients without ACE inhibition therapy. Our studies indicate an
      incomplete ACE inhibition in human heart tissue after chronic ACE inhibitor
      therapy. Moreover, ACE contributes only a small portion to the total Ang I
      conversion, as shown in biochemical studies in ventricular and coronary
      homogenates or functionally as Ang I contractions in isolated rings of coronary
      arteries. A serine protease was responsible for the majority of Ang II production
      in both the membrane preparation and Ang I-induced contractions of isolated
      coronary arteries. In humans, the serine protease pathway is likely to play an
      important role in cardiac Ang II formation. Thus, drugs such as renin inhibitors
      and Ang II receptor blockers might be able to induce a more complete blockade of
      the renin-angiotensin system, providing a more efficacious therapy.

PMID- 9012745
TI  - Angiotensin II and serum differentially regulate expression of cyclins, activity
      of cyclin-dependent kinases, and phosphorylation of retinoblastoma gene product
      in neonatal cardiac myocytes.
AB  - The hypertrophic response in cardiac myocytes and the mitogenic response in other
      cell types share various early cellular responses. However, how the subsequent
      cell growth response, such as cell cycle machinery, is regulated in cardiac
      hypertrophy is not understood. Using cultured neonatal rat cardiac myocytes, we
      examined the effect of angiotensin II (Ang II), a hypertrophic stimulus, on mRNA
      and protein expression of cyclins and cyclin-dependent protein kinases (cdks),
      activity of cdks, and phosphorylation of retinoblastoma gene product (pRb). The
      effect of FCS, a stimulus that was previously reported to initiate both protein
      and DNA synthesis in cardiac myocytes, was also examined for comparison. Ang II
      activated cdk4 and caused phosphorylation of pRb, peaking at 12 hours, but
      subsequently downregulated cyclin D1, D3, and A expression and cdk2 activity. FCS
      increased the expression of G1-S cyclins, caused activation of cdk4, cdk2, and
      cdc2, and strongly phosphorylated pRb but failed to significantly stimulate DNA
      synthesis in neonatal cardiac myocytes. These results suggest that Ang II
      transiently activates but subsequently downregulates cell cycle regulators.
      Induction of G1 and G1-S cyclins and activation of cdks by FCS are not sufficient
      to drive cardiac myocytes into S phase. The functional role of pRb
      phosphorylation by Ang II and serum stimulation and, by inference, the subsequent
      liberation of E2F in terminally differentiated myocytes remain to be elucidated.

PMID- 9012746
TI  - Termination of reentry by lidocaine in the tricuspid ring in vitro. Role of cycle
      length oscillation, fast use-dependent kinetics, and fixed block.
AB  - We hypothesized that drugs with rapid recovery kinetics from use-dependent sodium
      channel block could promote oscillatory termination of reentry by enhancing
      interval-dependent conduction. Mechanisms of termination were related to
      properties of the reentrant circuit. Nine adjustable reentrant preparations were
      used in which the canine atrial tricuspid ring was cut and then reconnected
      electronically by sensing activation on one side of the cut and pacing the other
      after an adjustable delay. The cycle length and diastolic interval during reentry
      were manipulated by changing this delay. Lidocaine (1.28 x 10(-5) mol/L)
      significantly increased refractoriness (94 +/- 39 ms) and the slope of the
      conduction curve (-0.12 +/- 0.07) at the site of block during pacing. Lidocaine
      terminated sustained reentry by two mechanisms. Early termination resulted from
      increased cycle length oscillation and refractoriness (reproducible in each
      experiment) but only at short delays with short initial diastolic intervals. The
      range of delays showing this mechanism of termination was 100 +/- 48 ms.
      Increased cycle-length oscillation resulted from an increased slope of the
      conduction curve. In eight experiments, lidocaine terminated reentry by causing
      fixed block after 50 minutes of drug superfusion, which prevented reentry at all
      delays. Fixed block occurred at one of two vulnerable sites and was transiently
      reversed by acetylcholine. Termination due to refractory block occurred only when
      the initial diastolic interval was short, and termination due to fixed block
      developed when there was a susceptible region with a low safety factor for
      propagation. Fast recovery from sodium channel block promotes oscillatory
      termination by increasing the slope of the conduction curve.

PMID- 9012747
TI  - Modulation by pH0 and intracellular Ca2+ of Na(+)-H+ exchange in diabetic rat
      isolated ventricular myocytes.
AB  - We have previously shown that diabetes is associated with a decrease in Na(+)-H+
      exchange activity in rat cardiac papillary muscle. The present work has been
      carried out in order to elucidate the factors responsible for such an alteration.
      Thus, we have studied the effects of pH0 and intracellular Ca2+ on Na(+)-H+
      exchange in ventricular myocytes isolated from streptozotocin-induced diabetic
      rat hearts. pH1 was recorded using carboxy-seminaphthorhodafluor (SNARF-1). The
      NH4+ (10 mmol/L) prepulse method was used to induce an acid load in order to
      activate Na(+)-H+ exchange in HEPES-buffered Tyrode's solution. Whereas diabetes
      did not change intracellular buffering power, it significantly decreased acid
      efflux through Na(+)-H+ exchange (acid efflux, 4.32 +/- 0.4 [n = 32, normal
      cells] versus 2.5 +/- 0.2 [n = 43, diabetic cells] meq/L per minute at pHi 6.9; P
      < .02). Upon changes of pH0 (at a range of 8.0 to 6.8), acid efflux similarly
      varied in normal and diabetic cells, thus pointing to an unchanged pH0
      sensitivity of Na(+)-H+ exchange. Buffering of intracellular Ca2+ by pretreatment
      of the cells with BAPTA-AM (25 mumol/L Ca2(+)-chelator) resulted in a decrease by
      approximately 58% of acid efflux in the diabetic group. This decrease was even
      more marked in normal cells (by approximately 74%). Interestingly, the pH1
      dependence of the acid efflux carried by Na(+)-H+ exchange then became identical
      in both groups of cells, thus pointing to a role for intracellular Ca2+ in the
      diabetes-related alterations of the exchange. Inhibition of calmodulin (by 1.5
      mumol/L calmidazolium) and of Ca2+/calmodulin-dependent protein kinase II (by 2
      mumol/L 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazin
      e [KN-62]) significantly slowed down pH1 recovery in both normal and diabetic
      cells. However, the effect of KN-62 was significantly lower in diabetic cells
      (efflux decreased by approximately 17%) compared with normal cells (decrease by
      45%). In conclusion, these data, in light of recent observations showing a
      decreased [Ca2+]i associated with diabetes in isolated ventricular myocytes,
      suggest that changes in intracellular Ca2+ may play an important role in altering
      Na(+)-H+ exchange activity in diabetic ventricular myocytes. They also point to
      diabetes-related alterations in the Ca2+/calmodulin protein kinase II-dependent
      phosphorylation of Na(+)-H+ exchange.

PMID- 9012748
TI  - Tissue and species distribution of mRNA for the IKr-like K+ channel, erg.
AB  - The human K+ channel gene, HERG, has been linked to the type 2 form of the
      autosomal dominant long-QT syndrome and has been suggested to encode the fast
      component of the delayed rectifier K+ current (IKr) found in heart. To date, the
      published electrophysiological and pharmacological data on the Xenopus-expressed
      HERG are very similar but are not identical to those of the endogenous IKr. In an
      effort to provide a different type of correlative data on the relationship
      between erg and IKr. cDNA fragments of erg homologues from guinea pig, rabbit,
      human, dog, and rat were cloned and used to test for the presence of erg mRNA in
      cardiac tissue. RNase protection assays reveal that erg message is found in the
      hearts of all five species and that it is expressed uniformly throughout the
      heart. The erg transcript is expressed at relatively high levels, being
      approximately 50% more abundant than the most prevalent Kv-class K+ channel
      transcript in canine ventricle (Kv4.3) erg transcripts were found to have a wide
      tissue distribution in rat and are abundant in the brain, retina, thymus, and
      adrenal gland and are also found in skeletal muscle, lung, and cornea. Since
      there were no published reports of an IKr-like current in the rat heart,
      electrophysiological studies were performed to test whether the significant level
      of erg message in rat heart was correlated with the presence of an IKr-like
      current in rat. In isolated rat ventricular myocytes, an E-4031-sensitive current
      was observed, which is consistent with the presence of IKr. These results
      strengthen the link between erg and the native IKr in heart and suggest that erg
      may play an important role in other noncardiac tissues.

PMID- 9012749
TI  - Dystrophin is not a specific component of the cardiac costamere.
AB  - Dystrophin is a key component of the subsarcolemmal skeleton of muscle cells, and
      lack of dystrophin is the direct cause of Duchenne muscular dystrophy. In
      skeletal muscle, dystrophin is reported to be localized specifically at
      costameres, transversely oriented riblike subsarcolemmal plaques that
      mechanically couple the contractile apparatus to the extracellular matrix.
      Costameres are characteristically rich in vinculin and are prominent in cardiac
      as well as skeletal muscle. To define the precise spatial relationship between
      dystrophin in relation to the costamere in cardiac muscle, we applied high
      resolution single- and double-immunolabeling techniques, under a range of
      preparative conditions, with visualization of vinculin (as a costamere marker)
      and dystrophin by confocal microscopy and by the freeze-fracture cytochemical
      technique, fracture label. Immunoconfocal visualization revealed dystrophin as a
      continuous uniform layer at the cytoplasmic surface of the peripheral plasma
      membrane of the rat cardiac myocyte at both costameric and noncostameric regions.
      The pattern of labeling was reproducible with three different antibodies and was
      independent of time and antibody concentration. Platinum/carbon replicas and thin
      sections of fracture-label specimens permitted high-resolution visualization of
      the distribution of dystrophin in plane views of the freeze-fractured plasma
      membrane and in relation to the sarcomeric banding patterns of the underlying
      myofibrils. These results confirmed no preferential association of dystrophin
      with costameres or with any region of the sarcomeres of underlying myofibrils in
      rat cardiac tissue. We conclude that in contrast to skeletal muscle, dystrophin
      in cardiac muscle is not exclusively a component of the costamere.

PMID- 9012750
TI  - Cytoskeletal mechanics in pressure-overload cardiac hypertrophy.
AB  - We have shown that the cellular contractile dysfunction characteristic of
      pressure-overload cardiac hypertrophy results not from an abnormality intrinsic
      to the myofilament portion of the cardiocyte cytoskeleton but rather from an
      increased density of the microtubule component of the extramyofilament portion of
      the cardiocyte cytoskeleton. To determine how, in physical terms, this increased
      microtubule density mechanically overloads the contractile apparatus at the
      cellular level, we measured cytoskeletal stiffness and apparent viscosity in
      isolated cardiocytes via magnetic twisting cytometry, a technique by which
      magnetically induced force is applied directly to the cytoskeleton through
      integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide.
      Measurements were made in two groups of cardiocytes from cats with right
      ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from
      the pressure-overloaded RV and (2) those from the normally loaded same-animal
      control left ventricle (LV). Cytoskeletal stiffness increased almost twofold,
      from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/-
      1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent
      viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally
      loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV
      cardiocytes. In addition to these baseline data showing differing stiffness and,
      especially, apparent viscosity in the two groups of cardiocytes, microtubule
      depolymerization by colchicine was found to return both the stiffness and the
      apparent viscosity of the pressure overload-hypertrophied RV cells fully to
      normal. Conversely, microtubule hyperpolymerization by taxol increased the
      stiffness and apparent viscosity values of normally loaded LV cardiocytes to the
      abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus,
      increased microtubule density constitutes primarily a viscous load on the
      cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

PMID- 9012751
TI  - The giant protein titin. Emerging roles in physiology and pathophysiology.
AB  - Titin is a giant protein of vertebrate striated muscles (M(r), > or = 3000 kD).
      Its molecules are of filamentous shape and span from the Z disk to the M line,
      thereby forming a third filament system of the sarcomere. This filament system is
      important for both the structural integrity of the myofibril and the passive
      tension response of a stretched muscle fiber. The determination of the cDNA
      sequence of human cardiac titin has shown that the cardiac titin filament is
      formed by a single, giant. 27,000-residue-long polypeptide chain. The titin
      strand has a modular structure, and different modular arrangements are expressed
      in different muscle tissue types by differential splicing. In the A band, the
      titin modules provide regular arrays of binding sites for other sarcomeric
      proteins, thereby contributing to a precise assembly of myofibrillar proteins in
      vivo. In the I band, two specific motif families, tandem-immunoglobulin domains
      and PEVK-rich sequences, confer extensibility to the titin filament. Expression
      of muscle tissue-specific length variants of the PEVK region by alternative
      splicing may explain the differences in the passive tension properties between
      various striated muscle types. Apart from the titin sequences with apparent
      functions for muscle structure and elasticity, the titin molecule contains a
      class of unique sequence insertions. Among these sequences are phosphorylation
      sites, a serine/threonine kinase domain, and binding sites for muscle-specific
      calpain proteases. Thus, it is likely that the titin filament also plays a role
      in myofibrillar signal transduction pathways.

PMID- 9012752
TI  - Microtubules and pressure-overload hypertrophy.

PMID- 9012753
TI  - Mechanisms of inflammation and leukocyte activation.
AB  - This article reviews the current status of the knowledge of mechanisms of
      activating inflammatory responses. It also describes inflammatory mediators,
      adhesion proteins, the inflammatory process itself, and the molecular mechanisms
      controlling inflammatory cell activation and regulation.

PMID- 9012754
TI  - Pathogenesis of rheumatoid arthritis.
AB  - Chronicity and destructive potential are characteristic features of the
      inflammatory response in the synovial membrane typical for RA. The dominant
      paradigm has proposed that an exogenous antigen, likely an infectious organism,
      targets the synovia and elicits a chronic immune response. Support for this
      disease model has come from describing the cellular components of the
      inflammatory lesions, which are composed of macrophages, T cells, and B cells.
      The observation that HLA molecules function by specifically binding antigenic
      peptides and presenting them to T cells has boosted the concept of an antigen
      driven response. The last decade in RA research has been dominated by a shift
      from premolecular to molecular techniques. A major effort has been made to
      determine which cytokines and inflammatory mediators are produced at the site of
      disease. Tissue residing and infiltrating cells secrete proinflammatory cytokines
      in situ, which likely have a critical role in amplifying and maintaining the
      inflammation. We are beginning to understand that migration of inflammatory cells
      into the tissue is an important component of disease, specifically because
      adhesion molecules not only facilitate tissue infiltration, but also affect cell
      activation and cell-cell and cell-matrix interactions. The paradigm that RA is an
      antigen-driven and thus T cell-mediated disease has brought attempts to use T
      cell-depleting reagents as therapeutics. Although T cells could be eliminated in
      the peripheral blood, overall therapeutic benefits have been minimal and
      accompanied by major side effects. The lack of therapeutic efficacy has been
      demonstrated to be combined with the persistence and the selective proliferation
      of T cells in the joint, reemphasizing the role of tissue-infiltrating T cells in
      the disease. Studies of the composition of the T cell infiltrate have
      demonstrated heterogeneity, indicating that disease-relevant T cells are probably
      low in frequency. A new perspective on the role of T cells in RA has been opened
      by studies establishing that RA patients select a unique repertoire of T cells in
      the thymus and that clonal expansion of CD4 T cells is a frequent event in RA
      patients. Pathology of T cell function might be much more systemic than suspected
      so far. RFs remain the major autoantibodies in RA patients. In the last 10 years,
      it has become clear that they are not exclusively built under pathologic
      conditions but that RF-expressing B cells are an important element of normal
      immune responses. All immunoglobulin isotypes are represented among RF molecules.
      Some of them have accumulated somatic mutations, suggesting the influence of
      antigen recognition and T cell help. T cell control of RF production may explain
      the observation that RF positivity is an HLA-dependent phenomenon. Major progress
      in understanding pathologic events leading to RA can be expected by abandoning
      single hit models, which are too simplified and underestimate the complexity of
      the disease. In particular, taking into account that nonimmune tissues and
      mechanisms might be equally important in pathogenesis will open new avenues of
      conceptual approaches. Cross-fertilization will likely come from genetic studies
      aimed at detecting underlying genetic risk factors in common genetic disease.
      Emerging data indicate that several genetic risk determinants, each of which is
      nonpathologic if occurring alone, can add up to confer disease risk. One of these
      genetic elements in RA has been mapped to the HLA region. A sequence polymorphism
      in the HLA-DR B1 gene appears to be a strong genetic risk factor in several
      ethnic groups. Correlation of clinical presentation of RA and the inheritance of
      the RA risk gene suggests that the gene product is not necessary in disease
      initiation but functions by modulating disease pattern and severity. The next
      decade in RA research will be dedicated toward unraveling how genetic
      determinants can introduce pathology (e.g., how HLA genes can function as progre

PMID- 9012755
TI  - Treatment of rheumatoid arthritis.
AB  - The management of rheumatoid arthritis (RA) remains a challenging objective.
      Recent trends have led to the earlier and more "aggressive" treatment of patients
      with active disease. This change in outlook is largely the result of the
      recognition that significant damage can occur fairly soon after the onset of
      disease. This article reviews the currently available therapies, including a
      discussion of the benefits and side effects associated with individual agents. In
      addition, possible approaches to the treatment of RA will be reviewed.

PMID- 9012756
TI  - Pathogenesis and treatment of osteoarthritis.
AB  - OA represents the final common pathway of a number of pathologic processes. The
      challenge is to define and classify the subsets of OA to understand the causes
      and to devise specific therapies. Effective chondroprotective therapies will be
      most useful when applied to high-risk individuals before the emergence of
      symptomatic OA. This will be feasible only with an improved understanding of the
      complex interaction of genes and environment in the OA disease process. Moreover,
      identifying the heritable bases of this disease will provide insight into the
      molecular mechanisms of the complex pathway that results in OA. Clinicians who
      encounter and treat OA patients can look forward to the development of more
      effective and innovative therapies based on a rapidly improving understanding of
      OA.

PMID- 9012757
TI  - Systemic lupus erythematosus. Diagnosis and treatment.
AB  - Systemic lupus erythematosus is a multisystem inflammatory disease characterized
      by antinuclear antibody production. The diagnosis of this disease is established
      on the basis of a constellation of clinical and serologic features. Therapy is
      directed to specific disease manifestations and involves an array of anti
      inflammatory and immunosuppressive agents that are administered judiciously to
      limit toxicity.

PMID- 9012758
TI  - Scleroderma and related conditions.
AB  - Systemic sclerosis is a generalized disorder characterized by fibrosis and
      microvascular injury in affected organs. Despite being recognized nearly 250
      years ago, knowledge regarding pathogenesis remains limited, and treatment
      remains directed at symptomatic improvement. Early recognition of systemic
      sclerosis, however, is important in order to monitor for specific disease
      complications (i.e., fibrosing alveolitis, scleroderma renal crisis) as well as
      initiate manifestation specific therapies that improve quality of life.

PMID- 9012759
TI  - Pathogenesis and treatment of the antiphospholipid antibody syndrome.
AB  - Antiphospholipid antibody syndrome (APS) is one of the most important causes of
      thrombophilia, presenting most often as venous or arterial thrombosis, recurrent
      pregnancy loss, or thrombocytopenia. Both the lupus anticoagulant and
      anticardiolipin antibody are associated with APS. The mechanism of the
      prothrombotic state is not understood, but may involve beta-2 glycoprotein 1 (a
      naturally occurring anticoagulant), platelet aggregation, the protein C pathway,
      or endothelial cell function. The current treatment recommendation, after a
      venous or arterial thrombosis, is high-intensity, long-term warfarin therapy.

PMID- 9012760
TI  - Diagnosis and treatment of Lyme arthritis.
AB  - Lyme arthritis typically causes intermittent attacks of oligoarticular arthritis
      in a few large joints, especially the knee. A small percentage of patients may
      develop chronic arthritis, again affecting primarily the knee. The diagnosis is
      usually based on the presence of this characteristic clinical picture, exposure
      in an endemic area, and a positive IgG antibody response to B. burgdorferi
      determined by ELISA and Western blotting. In addition, spirochetal DNA can often
      be detected in joint fluid by PCR. Joint involvement in this infection can
      usually be treated successfully with a 1- or 2-month course of oral doxycycline
      or amoxicillin, but patients with certain genetic and immune markers may have
      persistent arthritis despite treatment with oral or intravenous antibiotics. If
      patients have persistent arthritis despite a second course of antibiotics and if
      the results of PCR testing are negative, the author treats such patients with
      anti-inflammatory agents or arthroscopic synovectomy.

PMID- 9012761
TI  - Giant cell arteritis and polymyalgia rheumatica.
AB  - Giant cell arteritis and polymyalgia rheumatica are linked conditions that
      frequently occur in the same patient. They are more common in northern Europe and
      persons of European descent than in other populations. Recent investigations have
      begun to provide information about the pathogenesis of both syndromes. Both
      respond to corticosteroids but at different dose levels. Although a number of
      vascular complications may occur, the outlook is excellent.

PMID- 9012762
TI  - Pathogenesis of vasculitis syndromes.
AB  - The pathogenesis of vasculitis is complex and involves a variety of mechanisms
      acting in concert to bring about necrotizing inflammation of blood vessel walls.
      In recent years, there has been considerable progress in dissecting the
      immunologic abnormalities present in specific vasculitis syndromes. The primary
      immunopathogenic events that initiate the process of vascular inflammation and
      blood vessel damage, however, are still largely unknown. Although the cause of
      most vasculitis syndromes remains a mystery, advances in molecular and cellular
      immunology have defined many of the effector mechanisms that mediate inflammatory
      vascular damage. In this regard, modulation of the inflammatory response by
      specific cytokine and adhesion molecule antagonists is now possible and may prove
      beneficial in the treatment of vasculitis.

PMID- 9012763
TI  - Diagnosis and treatment of the systemic and cutaneous necrotizing vasculitis
      syndromes.
AB  - Advances in understanding of the spectrum of clinical presentations of patients
      with systemic and cutaneous necrotizing vasculitis as well as further work on
      pathogenesis of these conditions has helped with diagnosis of these conditions.
      Therapies for systemic and cutaneous necrotizing vasculitis are based on disease
      extent, severity, and concomitant conditions in the individual patient. Future
      multicenter and multidisciplinary studies will provide improved treatments for
      these challenging clinical situations.

PMID- 9012764
TI  - Arthritis syndromes associated with human T cell lymphotropic virus type I
      infection.
AB  - Arthritis syndromes occur associated with HTLV-I infection both in the presence
      and in the absence of clinical ATL, and polyarthritis may be the presenting
      manifestation of HTLV-I-associated ATL. In both clinical settings, HTLV-I
      infected T cells home to affected joints, and tax-transgenic mouse studies have
      suggested a pathogenic role for the HTLV-I tax gene in inducing synovial cell
      proliferation in HAA. Understanding the pathogenesis of rheumatoid arthritis-like
      arthritis syndromes that occur in the setting of HTLV-I infection should also
      provide insights into understanding of cellular and molecular mechanisms of
      synovial cell proliferation in HTLV-I-negative rheumatoid arthritis.

PMID- 9012765
TI  - Cognitive behavioral control of arthritis pain.
AB  - Cognitive-behavioral approaches appear to offer a viable alternative for the
      management of arthritis pain. Controlled studies have documented the efficacy of
      CBT protocols for managing pain in individuals having OA and RA. Preliminary
      studies examining the efficacy of CBT for FM patients have also yielded
      encouraging results. A number of clinical and research issues need attention if
      CBT is to be incorporated into rheumatology practice settings. These issues
      include identifying the most important components of CBT, developing strategies
      for matching CBT interventions to patients' readiness for behavior change,
      testing the efficacy of different therapy formats (e.g., individual versus
      group), broadening the scope of CBT to address issues other than pain, and
      insurance reimbursement.

PMID- 9012766
TI  - Transferring evidence from research into practice: 2. Getting the evidence
      straight.

PMID- 9012767
TI  - The safety assessment of novel foods. Guidelines prepared by ILSI Europe Novel
      Food Task Force.
AB  - The diversity of novel foods and novel ingredients covered by the scope of the EU
      regulation is such that a check list approach to safety evaluation is
      inappropriate. Rather, a case-by-case approach is required taking into account
      the composition of the novel food, its intake, its role in the diet and the
      intended target group. The SAFEST approach provides a means of targeting the
      safety evaluation on those aspects, nutritional or toxicological, of a novel food
      which are of particular concern. Using this approach, novel foods are assigned to
      one of three classes on the basis of certain background information. For those
      novel foods which can be shown to be in SAFEST class 1, namely those which are
      substantially equivalent to a traditional counterpart, no further information is
      required to demonstrate their safety. For those novel foods in SAFEST class 2,
      i.e. those sufficiently similar to a traditional counterpart or differing from it
      only in particular, well defined, characteristics, the evaluation will focus on
      those differences. Only in the case of novel foods which are not in class 1 or
      class 2 is extensive testing of the whole food likely to be required. Even in
      these cases, the testing should follow a scientifically-based hierarchical
      approach involving: literature reviews; chemical analysis; appropriate in vitro
      and in vivo tests; and, if necessary, confirmation of safety and nutritional
      value in humans. Examination of the causes of any adverse effects reported by
      consumers after the novel food or ingredient has been approved and is introduced
      into the market may provide additional reassurance of safety.

PMID- 9012768
TI  - Genotoxicity and subchronic toxicity studies with heated olestra.
AB  - Olestra is a class of sucrose-fatty acid polyesters intended for use as a non
      caloric replacement of edible oil. Genotoxicity and subchronic toxicity studies
      were conducted to determine whether olestra could form genotoxic or toxic
      breakdown products during simulated commercial use. Heated olestra was prepared
      for these studies by batch-frying potato slices in olestra at 177-185 degrees C
      for 25-32 hr over 5-7 days. Genotoxicity of this previously heated olestra was
      assessed in four standard in vitro assays: (1) Salmonella mutagenesis (Ames
      test); (2) forward mutagenesis of mouse lymphoma cells at the thymidine kinase
      locus; (3) unscheduled DNA synthesis in rat hepatocytes; and (4) clastogenicity
      in cultured Chinese hamster ovary cells. These tests were conducted with
      previously heated olestra at concentrations up to at least 5 mg/ml both in the
      absence of exogenous bioactivation and, for assays (1), (2) and (4) with added
      liver microsomal (S-9) activation. The Ames and mouse lymphoma assays were
      performed with olestra (10 mg/ml and 23 mg/litre, respectively) either alone or
      emulsified with the non-toxic, non-ionic surfactant Pluronics F68, both in the
      presence and absence of metabolic activation. To test for clastogenicity in vivo,
      rats were administered previously heated olestra by gavage at 5 g/kg per day for
      up to 5 days and bone marrow cells were examined for chromosomal aberrations.
      Heated olestra lacked genotoxic activity detectable by the aforementioned assays.
      Heated olestra was fed to Fischer 344 rats at up to 10% of the diet (w/w) for 91
      days. Evaluation of survival, food consumption, feed efficiency, physical
      condition, body weight, organ weight, haematological and clinical chemistry
      parameters, and histomorphology revealed no adverse effects attributable to
      ingestion of heated olestra at exposure levels in excess of those anticipated for
      human consumption. It is concluded that olestra used as a deep-frying medium
      conveys no genotoxic or toxic hazard at anticipated levels of human consumption.

PMID- 9012769
TI  - Subacute toxicity of ergometrine maleate in rats.
AB  - Ergot alkaloids, produced by the fungus Claviceps purpurea, are found in small
      amounts in foodstuffs. The human disease ergotism, caused by high intake of ergot
      alkaloids, is well known; however, little is known about the toxicity of these
      compounds. The subacute toxicity of an ergot alkaloid, ergometrine maleate, was
      therefore studied. Sprague-Dawley rats were treated with 0, 2, 10, 50 and 250 mg
      ergometrine maleate/kg diet for 4 wk. Plasma glucose levels were decreased in
      females at 50 and 250 mg/kg. Thyroxin levels were decreased at 50 (males only)
      and 250 mg/kg. At the high dose level, organ weights of heart, liver, ovaries and
      kidneys were increased. In male rats a slight dose-related increase in the
      incidence of enlarged mediastinal lymph nodes and, to some extent, of enlarged
      parathymal lymph nodes, was seen. Histopathological examination revealed evidence
      of increased glycogen storage in the liver of animals treated with 250 mg/kg. The
      no-observed-effect level in this study was 10 mg/kg.

PMID- 9012770
TI  - Lethality induced by stannous chloride on Escherichia coli AB1157: participation
      of reactive oxygen species.
AB  - Stannous chloride (SnCl2) has been widely used in nuclear medicine as a reducing
      agent of pharmaceutical products radiolabelled with technetium-99m. To verify
      whether the lethality induced by this salt could be mediated by reactive oxygen
      species (ROS), Escherichia coli cultures were treated with SnCl2 in the presence
      of catalase, ROS scavengers or metal-ion chelators. The inactivation effect, as
      measured by survival determination, was abolished by thiourea, sodium benzoate,
      dipyridyl or catalase. The results suggest the participation of ROS, generated by
      a Fenton-like reaction, in the lethal effect induced by SnCl2.

PMID- 9012771
TI  - Protective effects of diallyl sulfide on acetaminophen-induced toxicities.
AB  - Diallyl sulfide (DAS), a major flavour component of garlic, is known to modulate
      drug metabolism and may protect animals from chemically induced toxicity and
      carcinogenesis. In this study the effects of DAS on the oxidative metabolism and
      hepatotoxicity induced by acetaminophen (APAP) in rats were investigated. In the
      hepatotoxicity evaluation of Fischer 344 rats there was a dose-dependent increase
      in the odds of mortality rate by APAP (P = 0.009); DAS treatment significantly
      protected rats from APAP-related mortality (P = 0.026). Liver toxicity determined
      by lactate dehydrogenase activity was significantly increased by APAP treatment
      (0.75 g/kg). Pretreatment with DAS protected animals from APAP-induced liver
      toxicity in a time- and dose-dependent fashion. Treatment of DAS (50 mg/kg) 3 hr
      after APAP dosing significantly (P < 0.05) protected rats from APAP-induced liver
      toxicity. The metabolism of APAP (50 microM) in vitro was significantly inhibited
      by DAS (0.3-1 mM) in liver microsomes isolated from F344 rats. As the effect of
      DAS on APAP-induced hepatotoxicity in vivo was observed only when DAS was
      administered before or shortly after (< 3 hr) APAP dosing, data suggested that
      the protective effect of DAS is mainly at the metabolic activation step of APAP.
      However, the possibility that DAS may also have effects on other drug metabolism
      systems, such as glutathione (GSH) and glutathione S-transferases, cannot be
      ruled out.

PMID- 9012772
TI  - Effect of the active principle of garlic--diallyl sulfide--on cell viability,
      detoxification capability and the antioxidation system of primary rat
      hepatocytes.
AB  - The objectives of this study were to investigate the effects of various
      concentrations and incubation time intervals of diallyl sulfide (DAS), an active
      principle of garlic, on cell viability, and glutathione (GSH) concentration and
      its related enzymes activities in rat hepatocytes. According to the results of
      lactate dehydrogenase (LDH) leakage and microscopic examination, 0.5 or 1 mM DAS
      treatment did not have any adverse effects on the viability of hepatocytes.
      Intracellular GSH contents of cells treated with 0.5 and 1 mM DAS (58.6 and 66.4
      nmol GSH/mg protein, respectively) were higher than in the controls (54.2 nmol
      GSH/mg protein), around 8-23%, at 24 hr of incubation; a significant difference
      (P < 0.05) was observed for 1 mM DAS treatment at 48 hr. This phenomenon is
      beneficial to the detoxification and antioxidation capabilities of hepatocytes.
      Further, when the hepatocytes were treated with 0.5 or 1 mM DAS, the activities
      of glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione
      reductase (GRd) were almost the same as those of the controls. On the other hand,
      treatment with 5 mM DAS was associated with a significant decrease (P < 0.05) in
      cell viability, namely in increased LDH leakage (50% at 24-hr treatment),
      significant changes in the morphology of the hepatocytes, low intracellular GSH
      level (45% lower than in the controls at 24-hr treatment), and low activities of
      GST, GPx and Grd.

PMID- 9012773
TI  - In vivo percutaneous absorption of acetochlor in the rhesus monkey: dose-response
      and exposure risk assessment.
AB  - Percutaneous absorption of three topical dose levels of [14C]acetochlor in the
      rhesus monkey were determined for exposure risk assessment. The topical doses
      were 30.7, 0.43 and 0.03 mg acetochlor in 40 microliters commercial formulation
      and aqueous dilutions thereof, spread over 10 cm3 skin surface area (lower
      abdominal). The dosing area was not covered. The skin application time was 24 hr.
      The dosed skin surface area was washed with 50% soap (Ivory Liquid) and water at
      the end of the 24-hr dosing period. An intravenous dose of 0.43 mg was also
      administered to determine the excretory kinetics of acetochlor in the rhesus
      monkey. The same four monkeys were used for all dose administrations.
      Bioavailability was determined by radioactivity disposition in blood, urine and
      faeces. Percutaneous absorption was 23.1 +/- 8.7, 17.3 +/- 5.9 and 4.9 +/- 1.4%
      for 0.03, 0.43 and 30.7 mg doses, respectively. Assuming a constant state of
      absorption, the hourly exposure flux (microgram/cm2/hr) was 0.03 +/- 0.01 for the
      0.03 mg dose (3 micrograms/cm2). Increasing the dose approximately 15-fold to
      0.43 mg (43 micrograms/cm2) resulted in a 10-fold increase in flux to 0.3
      microgram/cm2/hr. Increasing the dose a further 70-fold to 30.7 mg (3070
      micrograms/cm2) resulted in only another 21-fold increase in flux (6.3 +/- 1.8
      micrograms/cm2/hr). Thus, the efficiency of absorption (%) decreased with
      increased topical dose, but the amount (mass/flux) of acetochlor absorbed always
      increased with increased dose. Plasma levels of topical acetochlor at the high
      dose were detectable at 1 hr and continued at a relatively steady level through
      the 24-hr dosing period. After the skin surface wash (24 hr) plasma levels
      decreased but were still detectable at the last 168-hr sampling period.
      Acetochlor, recently EPA approved as an herbicide for corn crops, is
      carcinogenic; however, farmers will use half as much acetochlor/acre as other
      herbicides. The percutaneous absorption of acetochlor is equal to that of
      alachlor. Therefore, human exposure based on one-half usage suggests that human
      risk assessment should be one-half all other factors being equal.

PMID- 9012775
TI  - The local lymph node assay: status of validation.
AB  - For the prediction of skin sensitization potential of substances, the local lymph
      node assay (LLNA) is an alternative to the widely used guinea pig tests. Over a
      10-yr period this method has undergone extensive development, evaluation and
      validation. In this commentary, the quality of this validation is examined. It is
      concluded that the LLNA has successfully passed through all reasonable validation
      stages. It provides a reliable and relevant source of predictive skin
      sensitization data which, unlike results from guinea pig tests, are reproducible
      from laboratory to laboratory. Thus, it is now ready for acceptance as a viable
      and complete alternative to traditional methods, offering substantial
      opportunities for reduction in animal usage and improved animal welfare without
      compromising standards for the identification of significant skin sensitizers.

PMID- 9012774
TI  - The local lymph node assay: a viable alternative to currently accepted skin
      sensitization tests.
AB  - The prospective identification of skin sensitizing chemicals is a vital
      prerequisite for their proper risk management. Traditionally this has been
      achieved largely by the conduct of guinea pig assays such as the maximization and
      Buehler tests. These methods are recommended by the Organisation for Economic
      Cooperation and Development (OECD) and are required by the European Union (EU)
      for the evaluation of new substances. However, a novel mechanistically based
      method, the local lymph node assay (LLNA), has been the focus of substantial
      validation activity in recent years. This material is reviewed in this paper. It
      is shown that the LLNA has been validated successfully by five interlaboratory
      assessments as well as by comparisons with guinea pig tests and human data. The
      method also offers clear advantages to the user in terms of objectivity, time and
      cost, and delivers important animal welfare benefits. In consequence, it is
      recommended that the LLNA be formally adopted by the OECD in Guideline 406 and
      accepted by the EU and US EPA as a method suitable for the classification of the
      skin sensitizing potential of chemicals.

PMID- 9012776
TI  - Toxicity of chronic ethanol ingestion and superoxide radical formation on seminal
      vesicle of rats.
AB  - The toxic effects of chronic ethanol ingestion were evaluated in male adult rats
      for 300 days. The animals were divided into three groups: the controls received
      only tap water as liquid diet; the chronic ethanol ingestion group received only
      ethanol solution (30%) in semivoluntary research; and the withdrawal group
      received the same treatment as chronic ethanol-treated rats until 240 days, after
      which they reverted to drinking water. Chronic ethanol ingestion induced
      increased lipoperoxide levels and acid phosphatase activities in seminal
      vesicles. Cu-Zn superoxide dismutase (SOD) decreased from its basal level 70.8 +/
      3.5 to 50.4 +/- 1.6 U/mg protein at 60 days of chronic ethanol ingestion. As
      changes in GSH-PX activity were observed in rats after chronic ethanol ingestion,
      while SOD activities were decreased in these animals, it is assumed that
      superoxide anion elicits lipoperoxide formation and induces cell damage before
      being converted to hydrogen peroxide by SOD. Ethanol withdrawal induced increased
      SOD activity and reduced seminal vesicle damage, indicating that the toxic
      effects were reversible, since increased SOD activity was adequate to scavenge
      superoxide radical formation. Superoxide radical is an important intermediate in
      the toxicity of chronic ethanol ingestion.

PMID- 9012777
TI  - Simultaneous determination of acrolein, malonaldehyde and 4-hydroxy-2-nonenal
      produced from lipids oxidized with Fenton's reagent.
AB  - Ethyl linoleate, ethyl linolenate, ethyl arachidonate and cod liver oil were
      oxidized with Fenton's reagent. Acrolein, malonaldehyde and 4-hydroxynonenal
      formed were derivatized to N-methylpyrazoline, N-methylpyrazole and 5-(1'
      hydroxyhexyl)-1-methyl-2-pyrazoline with N-methylhydrazine, respectively. The
      derivatives were simultaneously analysed by gas chromatograph equipped with a
      fused silica capillary column and a nitrogen-phosphorus detector. The maximum
      amounts of acrolein (9.7 +/- 2.11 nmol/ml) and malonaldehyde (61.18 +/- 6.51
      nmol/ml) were formed from cod liver oil. The highest amount of 4-hydroxynonenal
      (6.83 +/- 0.53 nmol/ml) was produced from ethyl arathidonate.

PMID- 9012778
TI  - The Leon Golberg Memorial Lecture. Antioxidants and disease prevention.

PMID- 9012779
TI  - Method for measuring a comprehensive energy budget in a proliferating cell system
      over multiple cell cycles.
AB  - Isolated cell systems are now being used very effectively to study a range of
      important biochemical questions, but their energy metabolism has never been
      comprehensively investigated. We have developed a system, using J2E cells, which
      enables us to measure total ATP turnover and the contribution of various fuels
      and pathways to this total in a dynamic, proliferating preparation. Cells are
      cultured in 500 ml airtight glass containers which enables (1) the measurement of
      oxygen consumption, (2) the collection and measurement of 14CO2 production from
      labelled fuels, and (3) the measurement of metabolite utilization and production.
      Data on cell numbers are then used to produce a curve of cell number vs. time,
      the area under which (cell numbers x hour) is used as a base by which all
      measurements and experiments are compared. To our knowledge this is the first
      time a comprehensive energy budget has been measured in a proliferating cell
      system over a period that covers multiple cell cycles.

PMID- 9012780
TI  - Induced PAI-1 mRNA expression and targeted protein accumulation are early G1
      events in serum-stimulated rat kidney cells.
AB  - Expression of plasminogen activator inhibitor type-1 (PAI-1), a member of the
      SERPIN gene family that functions to regulate the plasmin-based pericellular
      proteolytic cascade, is growth state-regulated in normal rat kidney (NRK) cells
      (Ryan and Higgins, 1990, J. Cell. Physiol., 155:376-384; Ryan et al., 1996,
      Biochem. J., 314:1041-1046). Comparative analysis of arrest states induced in NRK
      cells upon exposure to serum-deficient (0.5% FBS) or serum-free culture
      conditions served to define the kinetics of PAI-1 gene expression and fate of de
      novo-synthesized PAI-1 protein. While cells rendered quiescent in serum-free or
      serum-deficient media were equivalent with regard to the time course of PAI-1
      mRNA induction, the level of expressed transcripts (27-fold vs. 12-fold) and
      accumulated saponin fraction PAI-1 protein (12-fold vs. 6-fold) were consistently
      greater in cells recruited into exponential growth phase from a serum-free as
      compared to a serum-deficient arrest condition. Relative PAI-1 mRNA abundance
      increased within 1-2 hr post-serum addition, was maximal at 4 hr, and declined
      rapidly thereafter; this time course of expression coupled with placement of
      entry into DNA synthetic phase at approximately 12 hr after stimulation indicates
      that PAI-1 induction is an early-to-mid G1 phase event. Induced PAI-1 protein was
      evident immunocytochemically within 2 hr of serum stimulation as a peripheral
      "rim" of accumulated protein restricted to the cellular ventral surface at the
      plane of the substrate. No PAI-1 was detected between individual cells suggesting
      that this protein may be targeted directly to the undersurface region. By 6 hr
      post-stimulation, the rim of PAI-1 deposition increased in intensity and
      broadened to occupy approximately 30 to 50% of the total undersurface area.
      Double-label immunocytochemistry indicated that accumulated PAI-1 was deposited
      in close proximity to, but not actually within, vinculin-containing focal contact
      structures. Potential functionality of induced PAI-1 expression to either the
      initiation or maintenance of the serum-stimulated phenotype was assessed using
      antibodies to PAI-1. The IgG fractions of two different antisera which neutralize
      the ability of PAI-1 to complex with and thereby inhibit the catalytic activity
      of urokinase plasminogen activator significantly reduced (by 25-35%) the
      incidence of cells displaying the serum-stimulated phenotype; antibodies that
      bind PAI-1 but do not block PAI-1 inhibitory activity were without effect. In
      view of the vagaries of antibody accessibility and in situ neutralizing activity
      (particularly in a region as structurally complex as the focal contact), these
      data may actually underestimate the importance of PAI-1 in maintaining the
      activated phenotype.

PMID- 9012781
TI  - Inhibition of colony formation of NIH 3T3 cells by the expression of the small
      molecular weight heat shock protein HSP27: involvement of its phosphorylation and
      aggregation at the C-terminal region.
AB  - The ectopic expression of the small molecular weight heat shock protein HSP27
      reportedly confers resistance to heat and other types of stress, but our recent
      findings indicated that it rendered human immortalized fibroblast cells (KMST-6)
      more sensitive to oxidative stress and caused irreversible growth arrest (Arata
      et al., 1995, J. Cell. Physiol., 163:458-465). To clarify the relationship
      between HSP27 and growth regulation, we investigated the effect of overexpression
      of HSP27 and its mutants on the growth potential of several cell lines. Mammalian
      expression vectors of the wild-type, hypophosphorylatable, or C-terminal deletion
      mutants of human HSP27 were constructed from the pRc/CMV plasmid that contained
      the neomycin-resistant gene. The plasmid was introduced into mouse fibroblasts
      (NIH 3T3), normal human fibroblasts (TIG-3), Chinese hamster ovary (CHO-K1), or
      mammary tumor cells (MCF-7), which were then selected in medium containing G418.
      The number of drug-resistant colonies was significantly decreased by transfection
      with the expression vector for wild-type HSP27 compared with vector alone,
      whereas the overexpression of HSP27 in CHO-K1 cells had essentially no effect.
      The expression vectors of an hypophosphorylatable mutant (pKSm, human HSP27 gene
      in which codons for Ser-15, -78, and -82 were converted to code for Gly by site
      directed mutagenesis) as well as C-terminal deletion mutants in which 12-36 amino
      acid residues from the C-terminus were deleted had no significant effect on the
      colony-forming efficiency of NIH 3T3 cells. Cells isolated from G418-resistant
      colonies formed by transfection of NIH 3T3 cells with the HSP27 expression vector
      expressed no detectable levels of wild-type HSP27 and did not form stable clonal
      transformants expressing high levels of HSP27 from NIH 3T3 cells. In contrast,
      several clones expressing high levels of HSP27 were obtained from CHO-K1 cells
      transfected with the HSP27 expression vector. In KMST-6 clones expressing high
      levels of HSP27, the wild-type HSP27 formed aggregates with a mean molecular mass
      of about 200 kDa as determined by gel filtration, and the size of the oligomers
      changed with oxidative stress. On the other hand, the size of aggregates of HSP27
      encoded by pKSm or C-terminal deletion mutants did not change. These observations
      indicated that the forced expression of wild-type HSP27 participates in
      inhibiting the growth of some cell types and that the inhibition may be
      associated with its phosphorylation and aggregation.

PMID- 9012782
TI  - Fluid flow induces enhancement of the Egr-1 mRNA level in osteoblast-like cells:
      involvement of tyrosine kinase and serum.
AB  - It is widely accepted that mechanical loading is necessary to construct the
      architecture of bone and to maintain bone mass. However, the mechanism of how
      bone cells respond to mechanical stimuli is not known. To clarify this, we
      stimulated osteoblast-like MC3T3E1 cells by mechanical shaking of the culture
      dishes and found that the level of the egr-1 gene, which is an early response
      gene induced by growth factors or serum and encodes a transcription factor,
      increased 15-45 min after the shaking, with a peak at 30 min. The egr-1 gene
      product increased 1 h after the shaking. The egr-1 gene elevation was not blocked
      by prior exposure to indomethacin, saralasin, Rp-cAMP, A23187, and colchicine,
      and it was blocked partially by cytochalasin D, H-7, and prolonged exposure to
      TPA. On the other hand, a prior incubation with cycloheximide, DRB, genistein,
      herbimycin A, and BAPTA/AM completely blocked the egr-1 gene level enhanced by
      shaking the culture dishes. Moreover, we found that in serum-deprived cells the
      egr-1 gene response to shaking was not induced. These results suggested that the
      egr-1 gene response is regulated at the transcriptional level and that it
      involves tyrosine kinase as well as labile or de novo protein and requires a
      particular level of intracellular calcium and serum.

PMID- 9012783
TI  - Endogenous GM-CSF is involved as an autocrine growth factor for human
      osteoblastic cells.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important
      modulator of hematopoietic cells. However, the role of GM-CSF in nonhematopoietic
      cells remains unclear. We have determined whether GM-CSF is an autocrine
      mitogenic factor for human osteoblastic (hOB) cells. We found by reverse
      transcriptase-polymerase chain reaction (RT-PCR) that hOB cells express
      constitutively both GM-CSF and the alpha and beta chains of the GM-CSF receptor
      (GMR). Immunocytochemistry showed that serum-starved hOB cells express both GM
      CSF and GMR alpha chain. Recombinant human (rh) GM-CSF induces a dose-dependent
      stimulation of hOB cell proliferation, showing that hOB cells have functional
      GMRs. A specific neutralizing GM-CSF antibody decreased the basal growth rate and
      suppressed cell proliferation induced by media conditioned by hOB cells,
      indicating that GM-CSF released by hOB cells is biologically active. Treatment of
      hOB cells with GM-CSF antisense (AS) oligonucleotide inhibited the endogenous GM
      CSF production as shown by ELISA and immunocytochemistry, whereas a random (R)
      sequence had no effect. AS oligonucleotides markedly inhibited hOB cell growth
      reversibly, whereas R oligonucleotides had no effect. AS was more effective than
      the anti-GM-CSF antibody, and the addition of rhGM-CSF did not rescue the
      inhibitory effect of AS on cell growth. The findings that human osteoblastic
      cells produce GM-CSF and express functional GMR constitutively and that
      suppression of endogenous GM-CSF results in inhibition of cell growth demonstrate
      that GM-CSF is involved as an autocrine growth factor for human osteoblastic
      cells.

PMID- 9012784
TI  - Expression of epidermal growth factor-related proteins in the aged adult mouse
      mammary gland and their relationship to tumorigenesis.
AB  - Mammary glands from female BALB/c mice of different ages and parity were screened
      for production of three epidermal growth factor (EGF) related transforming growth
      factors and their corresponding mRNAs. Glands were obtained from 2-26-month-old
      nulliparous, 4-26-month-old parous, and 2-8-month-old midpregnant mice. Reverse
      transcribed polymerase chain reaction (RT-PCR) was used to screen for mRNA from
      the transforming growth factor alpha (TGF alpha), cripto-1 (CR-1), and
      amphiregulin (AR) genes in extracts of whole mammary glands. TGF alpha, CR-1, and
      AR transcripts were detected in all of the mammary glands assayed. In situ
      hybridization was then used to localize these mRNAs among various cell types in
      sections of glands. TGF alpha mRNA levels were low in the mammary epithelium from
      young nulliparous mice, high in the stroma of midpregnant mammary glands, and
      highest in luminal epithelium of the aged glands. AR mRNA levels were high and
      remained unchanged in all developmental stages. CR-1 mRNA level increased with
      age and was detected primarily in epithelium, with some scattered expression in
      adjacent stroma. Finally, TGF alpha, CR-1, and AR proteins were immunolocalized
      in histological sections of mammary glands from the various developmental stages.
      TGF alpha was detected sporadically in midpregnant mice, with more conspicuous
      reactivity seen in 18-26-month-old mice (38% of mice). CR-1 immunoreactivity was
      detected in 100% of the 18-26-month-old glands but not in any other age groups.
      Strong AR immunoreactivity was observed in in all glands, including 100% of the
      18-26-month-old glands. Staining for all three of these growth factors was
      observed primarily in the epithelium, with some reactivity detected in the
      periductal fibroblasts. No significant difference was discerned between glands
      from nulliparous and parous animals. We also found intense CR-1 and AR mRNA
      expression and strong immunoreactivity in seven different carcinogen-induced and
      eight spontaneous mammary tumors. Our results demonstrate that these growth
      factors accumulate in significant amounts in the old gland of both nulliparous
      and parous mice. The observations suggest that these growth factors are
      positioned to contribute to abnormal development in the older mammary gland,
      predisposing them to tumorigenesis.

PMID- 9012785
TI  - Synergistic enhancement of EGF, but not HGF, stimulated hepatocyte motility by
      TGF-beta 1 in vitro.
AB  - The ability of TGF-beta 1 (transforming growth factor-beta 1) to suppress growth
      factor induced proliferation of many cell types in vitro is well documented;
      however, TGF-beta 1 increases within a similar time frame as the hepatocyte
      mitogens HGF (hepatocyte growth factor), EGF (epidermal growth factor), and TGF
      alpha (transforming growth factor-alpha) prior to hepatocyte proliferation during
      liver regeneration. This has raised the issue that TGF-beta 1 may have effects on
      hepatocytes additional to mito-inhibition and that these effects may be relevant
      to the regenerative process. To this end, we examined the effect of TGF-beta 1 on
      both the mitogenesis and the motility of growth factor stimulated primary rat
      hepatocytes and the hepatoblastoma cell line HepG2 in vitro. TGF-beta 1
      significantly enhanced the chemotactic motility of EGF or TGF-alpha, and not HGF,
      stimulated hepatocytes on a collagen I substratum. TGF-beta 1 was not chemotactic
      when added alone and decreased the DNA synthesis of all hepatocyte cultures to
      near control levels. HepG2 cells were chemotactic toward HGF, EGF, and TGF-beta 1
      alone and displayed an additive chemotactic response when TGF-beta 1 was added to
      either HGF or EGF. Additionally, HepG2 cells were refractory to the growth
      stimulatory effects of HGF or EGF and the growth inhibitory effects of TGF-beta
      1. Hepatocytes plated onto other collagen-containing substrates (collagen IV,
      Matrigel, or ECL, an entactin-collagen IV-laminin matrix), but not on fibronectin
      or laminin alone, also displayed enhanced EGF stimulated motility by TGF-beta 1.
      The data indicate that an additional, novel role for TGF-beta 1 during liver
      tissue remodeling following PHx may include the synergistic enhancement EGF
      stimulated hepatocyte motility responses, and this enhancement is observed only
      on collagen-containing extracellular matrices.

PMID- 9012786
TI  - TGF-beta 1 stimulates cultured human fibroblasts to proliferate and produce
      tissue-like fibroplasia: a fibronectin matrix-dependent event.
AB  - During wound repair, fibroblasts accumulate in the injured area until any defect
      is filled with stratified layers of cells and matrix. Such fibroplasia also
      occurs in many fibrotic disorders. Transforming growth factor-beta (TGF-beta), a
      promotor of granulation tissue in vivo and extracellular matrix production in
      vitro, is expressed during the active fibroplasia of wound healing and
      fibroproliferative diseases. Under usual tissue culture conditions, normal
      fibroblasts grow to confluence and then cease proliferation. In this study,
      culture conditions with TGF-beta 1 have been delineated that promote human
      fibroblasts to grow in stratified layers mimicking in vivo fibroplasia. When
      medium supplemented with serum, ascorbate, proline, and TGF-beta was added thrice
      weekly to normal human dermal fibroblasts, the cells proliferated and stratified
      up to 16 cell layers thick within the culture dish, producing a tissue-like
      fibroplasia. TGF-beta stimulated both DNA synthesis as measured by 3H-thymidine
      uptake and cell proliferation as measured by a Hoechst dye DNA assay in these
      postconfluent cultures. The stratification was dependent on fibronectin assembly,
      as demonstrated by anti-fibronectin antibodies which inhibited both basal and TGF
      beta-stimulated cell proliferation and stratification. Suppression of collagen
      matrix assembly in cell layers with beta-amino-proprionitrile (BAPN) did not
      inhibit basal or TGF-beta stimulated in vitro fibroplasia. BAPN did not interfere
      with fibronectin matrix assembly as judged by immunofluorescence microscopy.
      Thus, in concert with serum factors, TGF-beta stimulates postconfluent,
      fibronectin matrix-dependent, fibroblast growth creating a fibroplasia-like
      tissue in vitro.

PMID- 9012787
TI  - Pressure regulates osteoclast formation and MCSF expression in marrow culture.
AB  - One of the forces generated during skeletal loading is hydrostatic pressure. In
      the work presented here, the ability of increased pressure to influence
      recruitment of osteoclasts was evaluated. Murine marrow cultures, with pO2 and
      pCO2 kept constant, were subjected to either control (1.0 atm) or elevated (1.37
      or 2.0 atm) hydrostatic pressure. As compared to control, cultures pressurized
      for 6 days at 1.37 atm formed less osteoclast-like cells (OCLC) (71 +/- 6% of
      control, P < 0.0001). A similar degree of inhibition occurred in cultures exposed
      to pressure during days 2-4 only (62 +/- 6%), while treatment during days 5-7
      failed to inhibit the OCLC number relative to control (99 +/- 5%). Delivery of
      2.0 atm pressure on days 2-4 generated 52 +/- 4% OCLC compared to control. Since
      macrophage colony stimulating factor (MCSF)-dependent proliferation of osteoclast
      precursors occurs during the pressure-sensitive period, semiquantitative RT-PCR
      for MCSF mRNA was performed after 3 days in 1.37 atm (days 2-4). As compared to
      controls, pressure caused a decrease in mRNA coding for the membrane bound form
      of MCSF (71.2 +/- 4% (n = 25, P < or = 0.05), while the MCSF RT-PCR product
      representing the secreted form showed no consistent change. This lack of response
      of the soluble MCSF RT-PCR product was expected, as levels of bioassayable MCSF
      were not altered by pressure. Extrapolating these data to in vivo conditions
      suggests that load-bearing will inhibit the formation of osteoclasts.

PMID- 9012788
TI  - Single cell analysis of intracellular osteopontin in osteogenic cultures of fetal
      rat calvarial cells.
AB  - Osteopontin (OPN), a major component of the bone matrix, is expressed at
      different stages of bone formation. To determine possible relationships between
      OPN expression and stages of osteogenic cell differentiation, we have performed
      single cell analyses of intracellular OPN in early (proliferating), subconfluent
      (differentiating), and mature (mineralizing) cultures of fetal rat calvarial
      cells (FRCC) using a combination of flow cytometry and confocal microscopy. At
      each culture stage, a high proportion (60-98%) of cells were immunoreactive for
      OPN (OPN+ve). Each of these populations also included a small proportion of OPN
      ve cells which were characterized by their small size, low granularity, high
      proliferative capacity, and enhanced osteogenic potential. The OPN+ve cells
      displayed two distinct patterns of intracellular immunostaining: a perinuclear
      distribution typical of secreted proteins and a perimembrane distribution in
      which patches of OPN were concentrated at the cell surface. Perimembranous
      staining predominated in migrant cells, which contained greater than tenfold
      higher levels of OPN than nonmigrant cells as separated in a Boyden chamber. When
      cell proliferation was high (day 2), most cells were OPN + ve. At all culture
      stages the intensity of OPN staining was increased as cells progressed through
      the cell cycle. As cells differentiated and started to form matrix (days 4 and
      6), the mean cell expression of OPN was also increased (fourfold), independent of
      changes in total cell protein. However, despite the association of OPN with
      osteogenic cells, we were surprised to find that a high proportion (60%) of fetal
      skin fibroblasts were also immunoreactive for OPN. The expression of OPN by these
      cell populations was confirmed by RT-PCR, and a strong correlation was observed
      between the quantitative flow cytometry data and Western blot analysis of cell
      extracts in which the high and low phosphorylated isoforms of OPN were observed.
      These studies, therefore, have identified several phenotypes in FRCC cultures
      that are based on OPN expression: small OPN-ve cell populations enriched in
      osteogenic precursors, differentiating osteogenic cells that synthesize and
      secrete OPN, and migrating stromal cells characterized by a perimembranous OPN
      staining pattern.

PMID- 9012789
TI  - Les liaisons dangereuses: adhesion molecules do it statistically.

PMID- 9012791
TI  - Identification of the proteins of the yeast U1 small nuclear ribonucleoprotein
      complex by mass spectrometry.
AB  - Here we report the rapid identification of the proteins of the spliceosomal U1
      small nuclear ribonucleoprotein (snRNP) from the yeast Saccharomyces cerevisiae
      by searching mass spectrometric data in genomic sequence databases. The U1 snRNP,
      containing a histidine-tagged 70K protein, was isolated from cell extracts by
      anti m3G-cap immunoaffinity and subsequent nickel nitrilotriacetic acid
      chromatography. A U1 snRNP fraction containing 20 proteins was obtained. Further
      purification by glycerol gradient centrifugation identified nine U1 snRNP
      specific and six common proteins. The U1 snRNP proteins were partially sequenced
      by nanoelectrospray mass spectrometry, and their genes were identified in the
      data base via multiple peptide sequence tags. Apart from the already known common
      proteins D1, D3, F, and G, the D2 and E homologs were also identified. The same
      six common proteins were detected in core U2 snRNP, which was purified and
      analyzed separately. The biochemical association of these six proteins with yeast
      snRNPs is shown here for the first time. Intriguingly, the Sm B/B' homolog was
      not detected. In addition to the well characterized yeast U1 specific proteins
      [U1-70K (Snp1p), U1-A (Mud1p), Prp39p, and Prp40p] the homolog of the U1-C
      protein was identified together with four additional novel U1 specific proteins,
      which are not found in mammalian U1. This is the first time that the components
      of a multiprotein complex from an organism with a sequenced genome have been
      characterized by mass spectrometry. The technique should be applicable to any
      protein complex that can be biochemically purified from an organism whose genome
      is known.

PMID- 9012790
TI  - The dynamins: redundant or distinct functions for an expanding family of related
      GTPases?
AB  - In the 7 years since dynamin was first isolated from bovine brain in search of
      novel microtubule-based motors, our understanding of this enzyme has expanded
      significantly. We now know that brain dynamin belongs to a family of large
      GTPases, which mediate vesicle trafficking. Furthermore, this enzymatic activity
      is markedly increased through association with microtubules, acidic
      phospholipids, and certain regulatory proteins that contain Src homology 3 (SH3)
      domains. From functional, genetic, and cellular manipulations, it is now
      generally accepted that dynamin participates in the endocytic uptake of
      receptors, associated ligands, and plasma membrane following an exocytic event.
      These observations have confirmed at least one function of dynamin that was
      predicted from seminal studies on a pleiotropic mutant, shibire(ts) (shi(ts)) in
      Drosophila melanogaster. Of equal interest is the finding that there are multiple
      dynamin gene products, including two that are expressed in a tissue-specific
      manner, and they share marked homology with a larger family of distinct but
      related proteins. Therefore, it is attractive to speculate that the different
      dynamins may participate in related cellular functions, such as distinct
      endocytic processes and even secretion. In turn, dynamin could play an important
      role in cell growth, cell spreading, and neurite outgrowth. The purpose of this
      review is to enumerate on the expansive dynamin literature and to discuss the
      nomenclature, expression, and putative functions of this growing and interesting
      family of proteins.

PMID- 9012792
TI  - Discrimination of a single base change in a ribozyme using the gene for
      dihydrofolate reductase as a selective marker in Escherichia coli.
AB  - For use of ribozymes in vivo, it is desirable to select functional ribozymes in
      the cellular environment (in the presence of inhibitory factors and limited
      concentrations of mandatory Mg2+ ions, etc.). As a first step toward this goal,
      we developed a new screening system for detection in vivo of an active ribozyme
      from pools of active and inactive ribozymes using the gene for dihydrofolate
      reductase (DHFR) as a selective marker. In our DHFR expression vector, the
      sequence encoding either the active or the inactive ribozyme was connected to the
      DHFR gene. The plasmid was designed such that, when the ribozyme was active, the
      rate of production of DHFR was high enough to endow resistance to trimethoprim
      (TMP). We demonstrated that the active ribozyme did indeed cleave the primary
      transcript in vivo, whereas the inactive ribozyme had no cleavage activity. Cells
      that harbored the active-ribozyme-coding plasmid grew faster in the presence of a
      fixed concentration of TMP than the corresponding cells that harbored the
      inactive-ribozyme-coding plasmid. Consequently, when cells were transformed by a
      mixture that consisted of active- and inactive-ribozyme-coding plasmids at a
      ratio of 1:1, (i) mainly those cells that harbored active ribozymes survived in
      the presence of TMP and (ii) both active- and inactive-ribozyme-harboring cells
      grew at an identical rate in the absence of TMP, a demonstration of a positive
      selection system in vivo. If the background "noise" can be removed completely in
      the future, the selection system might usefully complement existing selection
      systems in vitro.

PMID- 9012793
TI  - Cloning of a trypanosomatid gene coding for an ornithine decarboxylase that is
      metabolically unstable even though it lacks the C-terminal degradation domain.
AB  - Mammalian ornithine decarboxylase (ODC) is among the most labile of cellular
      proteins, with a half-life of usually less than an hour. Like other short-lived
      proteins ODC is degraded by the 26S proteasome. Its degradation is not triggered
      by ubiquitination, but is stimulated by the binding of an inducible protein,
      antizyme. Truncations and mutations in the C terminus of mammalian ODC have been
      shown to prevent the rapid turnover of the enzyme, demonstrating the presence of
      a degradation signal in this region. Moreover, ODCs from the trypanosomatid
      parasites Trypanosoma brucei and Leishmania donovani, which lack this C-terminal
      domain, are metabolically stable, and recombination of T. brucei ODC with the C
      terminus of mammalian ODC confers a short half-life to the fusion protein when
      expressed in mammalian cells. In the present study we have cloned and sequenced
      the ODC gene from the trypanosomatid Crithidia fasciculata. To our knowledge,
      this is the first protozoan shown to have an ODC with a rapid turnover. The
      sequence analysis revealed a high homology between C. fasciculata ODC and L.
      donovani ODC, despite the difference in stability. We demonstrate that C.
      fasciculata ODC has a very rapid turnover even when expressed in mammalian cells.
      Moreover, ODC from C. fasciculata is shown to lack the C-terminal degradation
      domain of mammalian ODC. Our findings indicate that C. fasciculata ODC contains
      unique signals, targeting the enzyme for rapid degradation not only in the
      parasite but also in mammalian cells.

PMID- 9012794
TI  - Differential behavior of curved DNA upon untwisting.
AB  - We have synthesized DNA segments with different handedness, twisting and radii of
      curvature, and have analyzed the effect of untwisting on them. The results
      indicate that the dynamic behavior of curved DNA upon untwisting is strongly
      determined by the initial sequence-dependent DNA trajectory. In particular, DNA
      with the same radii but with opposite handedness of superhelix twisting can show
      very different conformational responses to ethidium bromide untwisting. Upon
      treatment with ethidium bromide, right-handed superhelixes decrease their twist
      and increase the planarity of the superhelix, while left-handed superhelixes
      increase twisting and decrease their degree of planarity.

PMID- 9012795
TI  - Conferring RNA polymerase activity to a DNA polymerase: a single residue in
      reverse transcriptase controls substrate selection.
AB  - The traditional classification of nucleic acid polymerases as either DNA or RNA
      polymerases is based, in large part, on their fundamental preference for the
      incorporation of either deoxyribonucleotides or ribonucleotides during chain
      elongation. The refined structure determination of Moloney murine leukemia virus
      reverse transcriptase, a strict DNA polymerase, recently allowed the prediction
      that a single amino acid residue at the active site might be responsible for the
      discrimination against the 2'OH group of an incoming ribonucleotide. Mutation of
      this residue resulted in a variant enzyme now capable of acting as an RNA
      polymerase. In marked contrast to the wild-type enzyme, the K(m) of the mutant
      enzyme for ribonucleotides was comparable to that for deoxyribonucleotides. The
      results are consistent with proposals of a common evolutionary origin for both
      classes of enzymes and support models of a common mechanism of nucleic acid
      synthesis underlying catalysis by all such polymerases.

PMID- 9012796
TI  - In vitro scanning saturation mutagenesis of an antibody binding pocket.
AB  - We have combined PCR mutagenesis with in vitro transcription/translation and
      ELISA for the rapid generation and characterization of antibody mutants. The PCR
      products are used directly as the template for the in vitro
      transcription/translation reactions and because no cloning steps are required,
      the in vitro saturation mutagenesis of one residue can be completed in duplicate
      within a week by a single investigator. In vitro scanning saturation mutagenesis
      was used to analyze the role and plasticity of six key contact residues (H:Tyr
      33, H:Asn-35, H:Tyr-50, H:Trp-100, L:Val-94, and L:Pro-96) in the binding pocket
      of a single chain Fv antibody derived from the 26-10 monoclonal antibody. A total
      of 114 mutant antibodies were produced; all 19 substitutions at each of the 6
      chosen positions. The mutants were analyzed for binding to digoxin, digitoxin,
      digoxigenin, and ouabain resulting in the generation of a comprehensive data base
      of 456 relative affinity values. Excellent agreement between the relative
      affinity values obtained with in vitro synthesized mutant antibodies and
      equilibrium affinity data obtained with previously reported purified mutant
      monoclonal antibodies was observed. Approximately 75% of the single amino acid
      mutants exhibited significant binding to one or more of the digoxin analogs.
      Mutations that alter and, in some cases, reverse specificity for the different
      digoxin analogs were identified. In vitro scanning saturation mutagenesis
      represents a new tool for protein structure-function and engineering studies and
      can be interfaced with laboratory automation so that an even higher throughput of
      protein mutants can be constructed and analyzed.

PMID- 9012797
TI  - Fetal mouse selenophosphate synthetase 2 (SPS2): characterization of the cysteine
      mutant form overproduced in a baculovirus-insect cell system.
AB  - A novel gene detected in mouse embryonic sites of hematopoiesis was cloned and
      shown to be a eukaryotic analog of the Escherichia coli selenophosphate
      synthetase gene. Unlike the E. coli enzyme, which is not a selenoprotein, the
      presence of selenocysteine in the mouse enzyme is indicated by a TGA codon in the
      open reading frame of the gene in a position corresponding to the essential
      cysteine of the E. coli enzyme. An ionized selenol group in place of a cysteine
      sulfhydryl group could render this mammalian selenocysteine-containing enzyme a
      more active catalyst. The native cDNA clone and also a mutant form containing a
      TGC (cysteine) codon in place of TGA were expressed in a baculovirus-insect cell
      system. Based on recovery of purified proteins, expression of the mutant enzyme
      was about 40 times higher than wild-type enzyme. The cysteine mutant enzyme
      exhibited selenophosphate synthetase activity in the assay that measures selenide
      dependent AMP formation from ATP. Although expression of wild-type enzyme has not
      been optimized, the mutant form of the fetal mouse enzyme can be produced in
      amounts sufficient for isolation in homogeneous form and precise physicochemical
      and mechanistic studies allowing direct comparison with the analogous cysteine
      containing prokaryotic enzyme.

PMID- 9012798
TI  - rRNA-like sequences occur in diverse primary transcripts: implications for the
      control of gene expression.
AB  - Many eukaryotic mRNAs contain sequences that resemble segments of 28S and 18S
      rRNAs, and these rRNA-like sequences are present in both the sense and antisense
      orientations. Some are similar to highly conserved regions of the rRNAs, whereas
      others have sequence similarities to expansion segments. In particular, four 18S
      rRNA-like sequences are found in several hundred different genes, and the
      location of these four sequences within the various genes is not random. One of
      these rRNA-like sequences is preferentially located within protein coding regions
      immediately upstream of the termination codon of a number of genes. Northern blot
      analysis of poly(A)+ RNA from different vertebrates (chicken, cattle, rat, mouse,
      and human) revealed that a large number of discrete RNA molecules hybridize at
      high stringency to cloned probes prepared from the 28S or 18S rRNA sequences that
      were found to match those in mRNAs. Inhibition of polymerase II activity, which
      prevents the synthesis of most mRNAs, abolished most of the hybridization to the
      rRNA probes. We consider the hypotheses that rRNA-like sequences may have spread
      throughout eukaryotic genomes and that their presence in primary transcripts may
      differentially affect gene expression.

PMID- 9012799
TI  - RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of
      phospholipase C beta by gamma-thio-GTP-Gq alpha.
AB  - RGS proteins constitute a newly appreciated and large group of negative
      regulators of G protein signaling. Four members of the RGS family act as GTPase
      activating proteins (GAPs) with apparent specificity for members of the Gi alpha
      subfamily of G protein subunits. We demonstrate here that two RGS proteins, RGS4
      and GAIP, also act as GAPs for Gq alpha, the G alpha protein responsible for
      activation of phospholipase C beta. Furthermore, these RGS proteins block
      activation of phospholipase C beta by guanosine 5'-(3-O-thio) triphosphate-Gq
      alpha. GAP activity does not explain this effect, which apparently results from
      occlusion of the binding site on G alpha for effector. Inhibitory effects of RGS
      proteins on G protein-mediated signaling pathways can be demonstrated by simple
      mixture of RGS4 or GAIP with plasma membranes.

PMID- 9012800
TI  - Drosophila TFIIE: purification, cloning, and functional reconstitution.
AB  - We present a physical and molecular genetic characterization of Drosophila
      melanogaster TFIIE (dTFIIE), a component of the basal RNA polymerase II
      transcription apparatus. We have purified dTFIIE to near homogeneity from nuclear
      extracts of Drosophila embryos and found that it is composed of two subunits with
      apparent molecular weights of 55 and 38 kDa. Peptide sequence information derived
      from the two subunits was used to isolate the corresponding cDNA clones,
      revealing that dTFIIE and human TFIIE share extensive amino acid similarity.
      Functional conservation was demonstrated by the ability of bacterially expressed
      dTFIIE to substitute for human TFIIE in an in vitro transcription assay
      reconstituted from purified components. Cytological mapping analysis shows that
      both subunits are encoded by single copy genes located on chromosome III.

PMID- 9012801
TI  - Polyphosphate kinase as a nucleoside diphosphate kinase in Escherichia coli and
      Pseudomonas aeruginosa.
AB  - Generation of a wide variety of nucleoside (and deoxynucleoside) triphosphates
      (NTPs) from their cognate nucleoside diphosphates (NDPs) is of critical
      importance in virtually every aspect of cellular life. Their function is
      fulfilled largely by the ubiquitous and potent nucleoside diphosphate kinase
      (NDK), most commonly using ATP as the donor. Considerable interest is attached to
      the consequence to a cell in which the NDK activity becomes deficient or over
      abundant. We have discovered an additional and possibly auxiliary NDK-like
      activity in the capacity of polyphosphate kinase (PPK) to use inorganic
      polyphosphate as the donor in place of ATP, thereby converting GDP and other NDPs
      to NTPs. This reaction was observed with the PPK activity present in crude
      membrane fractions from Escherichia coli and Pseudomonas aeruginosa as well as
      with the purified PPK from E. coli; the activity was absent from the membrane
      fractions obtained from E. coli mutants lacking the ppk gene. The order of
      substrate specificity for PPK was: ADP > GDP > UDP, CDP; activity with ADP was 2
      60 times greater than with GDP, depending on the reaction condition. Although the
      transfer of a phosphate from polyphosphate to GDP by PPK to produce GTP was the
      predominant reaction, the enzyme also transferred a pyrophosphate group to GDP to
      form the linear guanosine 5' tetraphosphate.

PMID- 9012802
TI  - A point mutation leads to altered product specificity in beta-lactamase
      catalysis.
AB  - beta-Lactamases are the primary cause of beta-lactam antibiotic resistance in
      many pathogenic organisms. The beta-lactamase catalytic mechanism has been shown
      to involve a covalent acyl-enzyme. Examination of the structure of the class A
      beta-lactamase from Bacillus licheniformis suggested that replacement of Asn-170
      by leucine would disrupt the deacylation reaction by displacing the hydrolytic
      water molecule. When N170L beta-lactamase was reacted with penicillins, a novel
      product was formed. We postulate that with leucine at position 170 the acyl
      enzyme undergoes deacylation by an intramolecular rearrangement (rather than
      hydrolysis) to form a thiazolidine-oxazolinone as the initial product. The
      oxazolinone subsequently undergoes rapid breakdown leading to the formation of N
      phenylacetylglycine and N-formylpenicillamine. This appears to be the first
      reported case where a point mutation leads to a change in enzyme mechanism
      resulting in a substantially altered product, effectively changing the product
      specificity of beta-lactamase into that of D-Ala-D-Ala-carboxypeptidase
      interacting with benzylpenicillin.

PMID- 9012803
TI  - Cell cycle arrest mediated by the MEK/mitogen-activated protein kinase pathway.
AB  - The mitogen-activated protein kinase (MAPK) cascade plays a crucial role in the
      transduction of extracellular signals into responses governing growth and
      differentiation. The effects of a specific inhibitor of the MAPK kinase
      (MEK)/MAPK pathway (PD98059) on nerve growth factor (NGF)-induced growth arrest
      and inhibition of cell cycle-dependent kinases (CDKs) have been examined.
      Treatment of NIH 3T3 cells expressing TRKA with PD98059 dramatically reversed the
      complete inhibition of growth of these cells caused by NGF. PD98059 also blocked
      the ability of NGF to inhibit the activities of CDK4 and CDK2, while partially
      preventing NGF induction of p21Cip1/WAF1. To independently evaluate the
      involvement of the MEK/MAPK pathway in growth arrest, an inducible activated form
      of the Raf-1 protooncogene (delta RAF-1:ER) was expressed in these cells.
      Activation of delta RAF-1:ER resulted in a prolonged increase in MAPK activity
      and growth arrest of these cells, with concomitant induction of p21Cip1/WAF1 and
      inhibition of CDK2 activity. These effects of delta RAF-1:ER activation were all
      reversed by treatment of cells with PD98059. These data indicate that in addition
      to functioning as a positive effector of growth, stimulation of the MEK/MAPK
      pathway can result in an inhibition of CDK activity and cell cycle arrest.

PMID- 9012804
TI  - Major proteinase movement upon stable serpin-proteinase complex formation.
AB  - To determine whether formation of the stable complex between a serpin and a
      target proteinase involves a major translocation of the proteinase from its
      initial position in the noncovalent Michaelis complex, we have used fluorescence
      resonance energy transfer to measure the separation between fluorescein attached
      to a single cysteine on the serpin and tetramethylrhodamine conjugated to the
      proteinase. The interfluorophore separation was determined for the noncovalent
      Michaelis-like complex formed between alpha 1-proteinase inhibitor (Pittsburgh
      variant) and anhydrotrypsin and for the stable complex between the same serpin
      and trypsin. A difference in separation between the two fluorophores of
      approximately 21 A was found for the two types of complex. This demonstrates a
      major movement of the proteinase in going from the initial noncovalent encounter
      complex to the kinetically stable complex. The change in interfluorophore
      separation is most readily understood in terms of movement of the proteinase from
      the reactive center end of the serpin toward the distal end, as the covalently
      attached reactive center loop inserts into beta-sheet A of the serpin.

PMID- 9012805
TI  - A mutation of the atrial natriuretic peptide (guanylyl cyclase-A) receptor
      results in a constitutively hyperactive enzyme.
AB  - Mutation of an invariant glutamate residue found within the catalytic domain of
      guanylyl cyclases resulted in a dramatic 14-fold increase in the activity of the
      guanylyl cyclase-A receptor. Even in the presence of Mn2+/Triton X-100, a
      treatment previously thought to yield hormone-independent and maximum cyclase
      activity, the mutant enzyme remained 7-fold more active; to our knowledge, this
      is the first example of a protein modification or of an added agent that
      significantly increases cyclase activity in the presence of Mn2+/Triton X-100.
      Intracellular concentrations of cGMP in cells expressing the mutant (E974A)
      cyclase were only marginally elevated by the addition of atrial natriuretic
      peptide, and in broken-cell preparations, the mutant enzyme also was relatively
      insensitive to ligand/regulatory nucleotide. The marked increase in cyclase
      activity was not due to a relief of protein kinase domain inhibition, since the
      point mutation caused 7- to 13-fold elevations in guanylyl cyclase-A activity
      when the protein kinase homology domain was deleted. The E974A mutation also
      altered the kinetics from positive cooperative to linear with respect to MnGTP,
      suggesting disruption of subunit-subunit interactions. Thus, a single point
      mutation within the catalytic domain of a guanylyl cyclase results in a
      constitutively hyperactive enzyme that is independent of protein kinase domain
      regulation.

PMID- 9012806
TI  - Activities of human recombination protein Rad51.
AB  - Homologous pairing and strand exchange, which are catalyzed by Escherichia coli
      RecA protein, are central to homologous recombination. Homologs of this protein
      are found in eukaryotes; however, little has been reported on the recombinase
      activities of the mammalian homologs, including the human protein, denoted
      HsRad51. For the studies described here, we purified HsRad51 form E. coli.
      Although the activities of HsRad51 and RecA were qualitatively similar in the
      presence of ATP, there were also striking differences. The stoichiometry of
      binding to DNA and the rate of renaturation of complementary strands were similar
      for the two proteins, but rates of ATP hydrolysis, homologous pairing, and
      subsequent strand exchange promoted by HsRad51 were less than 1/10 those of RecA.
      In addition, HsRad51 bound gamma-thio-ATP and formed stable presynaptic complexes
      that promoted renaturation as rapidly as RecA, but the recombinant human protein
      catalyzed neither strand exchange nor homologous pairing of a single strand with
      duplex DNA in the presence of the ATP analog. By contrast, RecA promoted both of
      the latter reactions in control experiments. These observations suggest that
      among RecA-like proteins, HsRad51 may be a variant in which homologous pairing
      and strand exchange are more closely linked to the hydrolysis of ATP.

PMID- 9012807
TI  - The human A33 antigen is a transmembrane glycoprotein and a novel member of the
      immunoglobulin superfamily.
AB  - The mAb A33 detects a membrane antigen that is expressed in normal human colonic
      and small bowel epithelium and > 95% of human colon cancers. It is absent from
      most other human tissues and tumor types. The murine A33 mAb has been shown to
      target colon cancer in clinical trials, and the therapeutic potential of a
      humanized antibody is currently being evaluated. Using detergent extracts of the
      human colon carcinoma cell lines LIM1215 and SW1222, in which the antigen is
      highly expressed, the molecule was purified, yielding a 43-kDa protein. The N
      terminal sequence was determined and further internal peptide sequence obtained
      following enzymatic cleavage. Degenerate primers were used in PCRs to produce a
      probe to screen a LIM1215 cDNA library, yielding clones that enabled us to deduce
      the complete amino acid sequence of the A33 antigen and express the protein. The
      available data bases have been searched and reveal no overall sequence
      similarities with known proteins. Based on a hydrophilicity plot, the A33 protein
      has three distinct structural domains: an extracellular region of 213 amino acids
      (which, by sequence alignment of conserved residues, contains two putative
      immunoglobulin-like domains), a single hydrophobic transmembrane domain, and a
      highly polar intracellular tail containing four consecutive cysteine residues.
      These data indicate that the A33 antigen is a novel cell surface receptor or cell
      adhesion molecule in the immunoglobulin superfamily.

PMID- 9012808
TI  - Ribonucleotide reductase in the archaeon Pyrococcus furiosus: a critical enzyme
      in the evolution of DNA genomes?
AB  - Ribonucleotide reductase (RNR), the enzyme responsible for deoxyribonucleotide
      synthesis, has been isolated from Pyrococcus furiosus, a deeply branching
      hyperthermophilic, strictly anaerobic archaeon. Its gene has been cloned,
      sequenced, and shown to harbor two insertions encoding inteins. The purified
      enzyme absolutely requires adenosylcobalamin for activity, a trait that defines
      it as a member of class II (adenosyl-cobalamin-dependent) prokaryotic RNRs. On
      the other hand, the archaeal RNR has significant amino acid sequence homology
      with class I (aerobic non-heme iron-dependent) and class III (anaerobic iron
      sulfur-dependent) RNRs present in eukaryotes and bacteria, respectively. It is
      proposed that this enzyme may be the closest possible relative of the original
      RNR, which allowed the key "RNA world" to "DNA world" transition, and that the
      different classes of present-day RNRs are the products of divergent evolution.

PMID- 9012809
TI  - The thioredoxin binding domain of bacteriophage T7 DNA polymerase confers
      processivity on Escherichia coli DNA polymerase I.
AB  - Bacteriophage T7 DNA polymerase shares extensive sequence homology with
      Escherichia coli DNA polymerase I. However, in vivo, E. coli DNA polymerase I is
      involved primarily in the repair of DNA whereas T7 DNA polymerase is responsible
      for the replication of the viral genome. In accord with these roles, T7 DNA
      polymerase is highly processive while E. coli DNA polymerase I has low
      processivity. The high processivity of T7 DNA polymerase is achieved through
      tight binding to its processivity factor, E. coli thioredoxin. We have identified
      a unique 76-residue domain in T7 DNA polymerase responsible for this interaction.
      Insertion of this domain into the homologous site in E. coli DNA polymerase I
      results in a dramatic increase in the processivity of the chimeric DNA
      polymerase, a phenomenon that is dependent upon its binding to thioredoxin.

PMID- 9012810
TI  - Probing the environment along the protein import pathways in yeast mitochondria
      by site-specific photocrosslinking.
AB  - Artificially aminoacylated suppressor tRNAs were used to introduce photoreactive
      amino acids into model mitochondrial precursor proteins to probe the environment
      along the protein import pathway. Amino acids with benzophenone side chains of
      various lengths [DL-2-amino-3-(p-benzoylphenyl)propanoic acid (1) and DL-2-amino
      5-(p-benzoylphenyl)pentanoic acid (2)] were incorporated at specific sites
      throughout the cytochrome b2-dihydrofolate reductase fusion proteins, pb2(220)
      DHFR and pb2 delta 19(220)-DHFR, which were destined for the intermembrane space
      and the matrix in mitochondria, respectively. In vitro import of pb2(220)-DHFR
      and pb2 delta 19(220)-DHFR bearing 1 or 2 into isolated yeast mitochondria was
      arrested so that the N terminus reached the intermembrane space or the matrix,
      respectively, while the DHFR domain remained at the mitochondrial surface. The
      matrix-targeted pb2 delta 19(220)-DHFR was photocrosslinked to Tom40 in the outer
      membrane, Tim44 in the inner membrane, and Ssc1p in the matrix, suggesting that
      the protein has an extended conformation in the import channels. On the other
      hand, incorporation of 2 at various positions in the 50-residue segment of
      intermembrane-space-targeted pb2(220)-DHFR gave photocrosslinks only to Tom40,
      suggesting that the segment is not in an extended conformation, but localized
      near Tom40. The N-terminal portion of pb2(220)-DHFR, but not pb2 delta 19(220)
      DHFR, was photocrosslinked to an as-yet-unidentified mitochondrial component to
      generate a 95-kDa crosslinked product.

PMID- 9012811
TI  - The role of phenylalanine in structure-function relationships of phenylalanine
      hydroxylase revealed by radiation target analysis.
AB  - The activity of rat liver phenylalanine hydroxylase (PAH; phenylalanine 4
      monooxygenase, EC 1.14.16.1) is regulated by interaction with its substrate,
      phenylalanine, and its coenzyme, BH4 [tetrahydrobiopterin (6R-dihydroxypropyl-L
      erythro-5,6,7,8-tetrahydropterin)]. The structural changes accompanying these
      interactions have been studied by radiation target analysis. PAH purified from
      rat liver was incubated with 2 mM phenylalanine to achieve complete activation of
      the enzyme. Frozen samples were irradiated with various doses of high energy
      electrons; samples were subsequently thawed, and several surviving properties of
      the enzyme were determined. Each parameter decreased as a single exponential
      function of radiation dose. Radiation target analysis of enzymatic activity
      yielded a dimeric target size. Similar radiation effects on subunit monomers and
      on tetrameric structure were observed. Together with results from unactivated
      enzyme, these data show that phenylalanine increases the interactions between the
      subunits in a dimer and weakens the interactions between dimers in a tetramer.
      These alterations prevent the natural cofactor, a tetrahydrobiopterin, from
      exerting a negative effect on activity.

PMID- 9012812
TI  - Visualization of supercoiled DNA with atomic force microscopy in situ.
AB  - Tertiary structure of supercoiled DNA is a significant factor in a number of
      genetic functions and is apparently affected by environmental conditions. We
      applied atomic force microscopy (AFM) for imaging the supercoiled DNA deposited
      at different ionic conditions. We have employed a technique for the sample
      preparation that permits high-resolution AFM imaging of DNA bound to the surface
      in buffer solutions without drying the sample (AFM in situ). The AFM data show
      that at low ionic strength, DNA molecules are loosely interwound supercoils with
      an irregular shape. Plectonemic superhelices are formed in high-concentration,
      near-physiological salt solutions. At such ionic conditions, superhelical loops
      are typically separated by regions of close helix-helix contacts. The data
      obtained show directly and unambiguously that overall geometry of supercoiled DNA
      depends dramatically on ionic conditions. This fact and the formation of close
      contacts between DNA helices are important features of supercoiled DNA related to
      its biological functions.

PMID- 9012813
TI  - Nuclear localization of cyclin B1 mediates its biological activity and is
      regulated by phosphorylation.
AB  - M-phase promoting factor or maturation promoting factor, a key regulator of the
      G2-->M transition of the cell cycle, is a complex of cdc2 and a B-type cyclin. We
      have previously shown that Xenopus cyclin B1 has five sites of Ser
      phosphorylation, four of which map to a recently identified cytoplasmic retention
      signal (CRS). The CRS appears to be responsible for the cytoplasmic localization
      of B-type cyclins, although the underlying mechanism is still unclear.
      Phosphorylation of cyclin B1 is not required for cdc2 binding or cdc2 kinase
      activity. However, when all of the Ser phosphorylation sites in the CRS are
      mutated to Ala to abolish phosphorylation, the mutant cyclin B1Ala is
      inactivated; activity can be enhanced by mutation of these residues to Glu to
      mimic phosphoserine, suggesting that phosphorylation of cyclin B1 is required for
      its biological activity. Here we show that biological activity can be restored to
      cyclin B1Ala by appending either a nuclear localization signal (NLS), or a second
      CRS domain with the Ser phosphorylation sites mutated to Glu, while fusion of a
      second CRS domain with the Ser phosphorylation sites mutated to Ala inactivates
      wild-type cyclin B1. Nuclear histone H1 kinase activity was detected in
      association with cyclin B1Ala targeted to the nucleus by a wild-type NLS, but not
      by a mutant NLS. These results demonstrate that nuclear translocation mediates
      the biological activity of cyclin B1 and suggest that phosphorylation within the
      CRS domain of cyclin B1 plays a regulatory role in this process. Furthermore,
      given the similar in vitro substrate specificity of cyclin-dependent kinases,
      this investigation provides direct evidence for the hypothesis that the control
      of subcellular localization of cyclins plays a key role in regulating the
      biological activity of cyclin-dependent kinase-cyclin complexes.

PMID- 9012814
TI  - The N-terminal propiece of interleukin 1 alpha is a transforming nuclear
      oncoprotein.
AB  - Interleukin 1 alpha (IL-1 alpha) is a pleiotropic cytokine involved in the immune
      response, inflammatory processes, and hematopoiesis, and acts as a mitogen for
      several malignant cell types, including acute leukemia and Kaposi sarcoma cells.
      These diverse activities have been exclusively attributed to the plasma membrane
      receptor-binding, 17-kDa C-terminal component (mature IL-1 alpha) that results
      from proteolytic processing of the 31- to 33-kDa precursor protein. No biologic
      function has been ascribed to the unusually large, 16-kDa N-terminal propiece
      formed as a result of proteolytic processing of IL-1 alpha. We report that the IL
      1 alpha N-terminal propiece is concentrated by means of a nuclear localization
      sequence within the nuclei of both transfected and leukemic cell lines.
      Overexpression of this component in glomerular mesangial cells, a model
      perivascular myofibroblast cell type capable of IL-1 alpha synthesis and
      processing, results in malignant transformation to a spindle cell-type tumor. The
      functionally bipartite nature of the IL-1 alpha precursor represents a unique
      combination of the C-terminal, classical cytokine and an N-terminal nuclear
      oncoprotein. These findings suggest that nuclear transport of the IL-1 alpha N
      terminal component may represent a critical component in the transformation of IL
      1 alpha-producing cells in the bone marrow or the perivascular area to a
      malignant phenotype.

PMID- 9012815
TI  - Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA
      damage in human cells following oxidative stress.
AB  - A significant amount of reactive oxygen species (ROS) is generated during
      mitochondrial oxidative phosphorylation. Several studies have suggested that
      mtDNA may accumulate more oxidative DNA damage relative to nuclear DNA. This
      study used quantitative PCR to examine the formation and repair of hydrogen
      peroxide-induced DNA damage in a 16.2-kb mitochondrial fragment and a 17.7-kb
      fragment flanking the beta-globin gene. Simian virus 40-transformed fibroblasts
      treated with 200 microM hydrogen peroxide for 15 or 60 min exhibited 3-fold more
      damage to the mitochondrial genome compared with the nuclear fragment. Following
      a 60-min treatment, damage to the nuclear fragment was completely repaired within
      1.5 hr, whereas no DNA repair in the mitochondrion was observed. Mitochondrial
      function, as assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide reduction, also showed a sharp decline. These cells displayed arrested
      cell growth, large increases in p21 protein levels, and morphological changes
      consistent with apoptosis. In contrast, when hydrogen peroxide treatments were
      limited to 15 min, mtDNA damage was repaired with similar kinetics as the nuclear
      fragment, mitochondrial function was restored, and cells resumed division within
      12 hr. These results indicate that mtDNA is a critical cellular target for ROS. A
      model is presented in which chronic ROS exposure, found in several degenerative
      diseases associated with aging, leads to decreased mitochondrial function,
      increased mitochondrial-generated ROS, and persistent mitochondrial DNA damage.
      Thus persistent mitochondrial DNA damage may serve as a useful biomarker for ROS
      associated diseases.

PMID- 9012816
TI  - Membrane specific mapping and colocalization of malarial and host skeletal
      proteins in the Plasmodium falciparum infected erythrocyte by dual-color near
      field scanning optical microscopy.
AB  - Accurate localization of proteins within the substructure of cells and cellular
      organelles enables better understanding of structure-function relationships,
      including elucidation of protein-protein interactions. We describe the use of a
      near-field scanning optical microscope (NSOM) to simultaneously map and detect
      colocalized proteins within a cell, with superresolution. The system we elected
      to study was that of human red blood cells invaded by the human malaria parasite
      Plasmodium falciparum. During intraerythrocytic growth, the parasite expresses
      proteins that are transported to the erythrocyte cell membrane. Association of
      parasite proteins with host skeletal proteins leads to modification of the
      erythrocyte membrane. We report on colocalization studies of parasite proteins
      with an erythrocyte skeletal protein. Host and parasite proteins were selectively
      labeled in indirect immunofluorescence antibody assays. Simultaneous dual-color
      excitation and detection with NSOM provided fluorescence maps together with
      topography of the cell membrane with subwavelength (100 nm) resolution.
      Colocalization studies with laser scanning confocal microscopy provided lower
      resolution (310 nm) fluorescence maps of cross sections through the cell. Because
      the two excitation colors shared the exact same near-field aperture, the two
      fluorescence images were acquired in perfect, pixel-by-pixel registry, free from
      chromatic aberrations, which contaminate laser scanning confocal microscopy
      measurements. Colocalization studies of the protein pairs of mature parasite
      infected erythrocyte surface antigen (MESA) (parasite)/protein4.1(host) and P.
      falciparum histidine rich protein (PfHRP1) (parasite)/protein4.1(host) showed
      good real-space correlation for the MESA/protein4.1 pair, but relatively poor
      correlation for the PfHRP1/protein4.1 pair. These data imply that NSOM provides
      high resolution information on in situ interactions between proteins in
      biological membranes. This method of detecting colocalization of proteins in
      cellular structures may have general applicability in many areas of current
      biological research.

PMID- 9012817
TI  - A p53-independent damage-sensing mechanism that functions as a checkpoint at the
      G1/S transition in Chinese hamster ovary cells.
AB  - In response to a moderate dose of radiation, asynchronous mammalian cell
      populations rapidly and transiently down-regulate the rate of DNA synthesis to
      approximately 50% of preirradiation values. We show here that only half of the
      reduction in overall replication rate can be accounted for by direct inhibition
      of initiation at origins in S-phase cells. The other half results from the
      operation of a newly defined cell cycle checkpoint that functions at the G1/S
      transition. This checkpoint senses damage incurred at any time during the last 2
      hr of G1 and effectively prevents entry into the S period. The G1/S and S-phase
      checkpoints are both p53-independent and, unlike the p53-mediated G1 checkpoint,
      respond rapidly to radiation, suggesting that they may represent major damage
      sensing mechanisms connecting the replication machinery with DNA repair pathways.

PMID- 9012818
TI  - Activation of human B-MYB by cyclins.
AB  - B-MYB expression is associated with cell proliferation and recent studies have
      suggested that it promotes the S phase of mammalian cells. Based on its homology
      to the transcription factors c-MYB and A-MYB, B-MYB is thought to be involved in
      transcriptional regulation; however, its activity is not detectable in several
      cell lines. It was postulated that B-MYB function may depend on the presence of a
      cofactor, and recent studies suggested that B-MYB is phosphorylated specifically
      during S phase in murine fibroblasts. In this report we provide evidence that the
      product of the human B-myb gene can be activated in vivo by coexpression with
      cyclin A or cyclin E. Transfection studies showed that B-MYB was a weak
      transcriptional activator in SAOS-2 cells and was unable to promote their
      proliferation. In contrast, overexpression of both B-MYB and cyclin A or cyclin E
      caused a drastic increase in the number of SAOS-2 cells in S phase. Also,
      overexpression of cyclin A and cyclin E in SAOS-2 cells enhanced the ability of B
      MYB, but not c-MYB, to transactivate various promoters, including the cdc2
      promoter, the HIV-1-LTR, and the simian virus 40 minimal promoter. A direct role
      for cyclin-dependent activation of B-MYB was demonstrated using an in vitro
      transcription assay. These observations suggest that one mechanism by which
      cyclin A and E may promote the S phase is through modification and activation of
      B-MYB.

PMID- 9012819
TI  - Mitosis-promoting factor-mediated suppression of a cloned delayed rectifier
      potassium channel expressed in Xenopus oocytes.
AB  - The cell cycle is the crucial process that leads to mitosis in all cell types.
      The dramatic redirectioning of many cellular processes during the cycle is known
      to involve ion channels, either changing their level of expression or their
      voltage dependence, as in the case of inward rectifiers. Here we describe the
      specific inhibition of heterologously expressed ionic channels at the onset of
      maturation in Xenopus oocytes. In cells expressing rat eag (R-eag) potassium
      channels, maturation induces a dramatic reduction in the current amplitude, which
      is almost complete in most cases. The key molecule in oocyte maturation, the
      mitosis-promoting factor (a complex of cyclin B and p34cdc2), is able to induce
      similar changes when injected into the oocytes.

PMID- 9012820
TI  - Effects of methionine on the cytoplasmic distribution of actin and tubulin during
      neural tube closure in rat embryos.
AB  - Research has previously shown that, without methionine supplements, neural tube
      proteins of rat embryos cultured on bovine sera were hypomethylated and neural
      tubes failed to close. In the present study, to identify the proteins that became
      methylated during neurulation, rat embryos were first cultured on methionine
      deficient bovine serum for 40 hr, then incubated with puromycin for 1 hr, and,
      finally, incubated with [methyl-14C]methionine and puromycin for 5 hr. On the
      basis of molecular weights, isoelectric points, and Western immunoblots, the
      methyl-14C-labeled proteins were identified as actin, alpha beta-tubulin, and
      neurofilament L. Indirect immunofluorescence studies indicated that without the
      addition of methionine to the culture, localization of actin and alpha beta
      tubulin in the basal cytoplasm did not occur and these neuroepithelial cells lost
      their columnar morphology.

PMID- 9012821
TI  - Immunocompetence, ornamentation, and viability of male barn swallows (Hirundo
      rustica).
AB  - Immunocompetence (i.e., the ability to produce an immune response to pathogens)
      can be predicted to influence the chances that organisms have to survive and
      reproduce. In this study we simulated a challenge to the immune systems of male
      barn swallows (Hirundo rustica) by injecting them intraperitoneally with a
      multigenic antigen, sheep red blood cells, and we analyzed long-term survival in
      relation to their immunocompetence. Males were assigned to four groups that
      differed for the treatment of the length of the outermost tail feathers, a
      sexually dimorphic ornamental character that is currently under directional
      sexual selection. Immunocompetence was measured as change of concentration of
      gamma globulins relative to plasma proteins. The intensity of the immune response
      was independent of age. Males that showed the highest short-term response to
      sheep red blood cells were more likely to survive until the breeding season
      following that in which they had been inoculated, a pattern consistently observed
      within each experimental group. Males with comparatively long tails were more
      likely to survive than those with short tails. To our knowledge, the results of
      this study are the first to demonstrate that immunocompetence can predict long
      term survival in a free-ranging vertebrate. Moreover, they are compatible with
      current models of parasite-mediated sexual selection because long-tailed males
      are more immunocompetent than short-tailed ones, and females, by preferring to
      mate with the most ornamented males, may acquire the "good genes" for high
      immunocompetence and, hence, for high viability of their offspring.

PMID- 9012822
TI  - Evolution of trans-splicing plant mitochondrial introns in pre-Permian times.
AB  - Trans-splicing in angiosperm plant mitochondria connects exons from independent
      RNA molecules by means of group II intron fragments. Homologues of trans-splicing
      introns in the angiosperm mitochondrial nad2 and nad5 genes are now identified as
      uninterrupted group II introns in the ferns Asplenium nidus and Marsilea
      drummondii. These fern introns are correctly spliced from the pre-mRNA at the
      sites predicted from their well-conserved secondary structures. The flanking exon
      sequences of the nad2 and nad5 genes in the ferns require RNA editing, including
      the removal of in-frame stop codons by U-to-C changes for correct expression of
      the genetic information. We conclude that cis-splicing introns like the ones now
      identified in ferns are the ancestors of trans-splicing introns in angiosperm
      mitochondria. Intron disruption is apparently due to a size increase of the
      structurally variable group II intron domain IV followed by DNA recombination in
      the plant mitochondrial genome.

PMID- 9012823
TI  - Inactivation of FtsI inhibits constriction of the FtsZ cytokinetic ring and
      delays the assembly of FtsZ rings at potential division sites.
AB  - A universally conserved event in cell division is the formation of a cytokinetic
      ring at the future site of division. In the bacterium Escherichia coli, this ring
      is formed by the essential cell division protein FtsZ. We have used
      immunofluorescence microscopy to show that FtsZ assembles early in the division
      cycle, suggesting that constriction of the FtsZ ring is regulated and supporting
      the view that FtsZ serves as a bacterial cytoskeleton. Assembly of FtsZ rings was
      heterogeneously affected in an ftsI temperature-sensitive mutant grown at the
      nonpermissive temperature, some filaments displaying a striking defect in FtsZ
      assembly and others displaying little or no defect. By using low concentrations
      of the beta-lactams cephalexin and piperacillin to specifically inhibit FtsI
      (PBP3), an enzyme that synthesizes peptidoglycan at the division septum, we show
      that FtsZ ring constriction requires the transpeptidase activity of FtsI.
      Unconstricted FtsZ rings are stably trapped at the midpoint of the cell for
      several generations after inactivation of FtsI, whereas partially constricted
      FtsZ rings are less effectively trapped. In addition, FtsZ rings are able to
      assemble in newborn cells in the presence of cephalexin, suggesting that newborn
      cells contain a site at which FtsZ can assemble (the nascent division site) and
      that the transpeptidase activity of FtsI is not required for assembly of FtsZ at
      these sites. However, aside from this first round of FtsZ ring assembly, very few
      additional FtsZ rings assemble in the presence of cephalexin, even after several
      generations of growth. One interpretation of these results is that the
      transpeptidase activity of FtsI is required, directly or indirectly, for the
      assembly of nascent division sites and thereby for future assembly of FtsZ rings.

PMID- 9012824
TI  - Identification of protein coding regions in the human genome by quadratic
      discriminant analysis.
AB  - A new method for predicting internal coding exons in genomic DNA sequences has
      been developed. This method is based on a prediction algorithm that uses the
      quadratic discriminant function for multivariate statistical pattern recognition.
      Substantial improvements have been made (with only 9 discriminant variables) when
      compared with existing methods: HEXON [Solovyev, V. V., Salamov, A. A. &
      Lawrence, C. B. (1994) Nucleic Acids Res. 22, 5156-5163] (based on linear
      discriminant analysis) and GRAIL2 [Uberbacher, E. C. & Mural, R. J. (1991) Proc.
      Natl. Acad. Sci. USA 88, 11261-11265] (based on neural networks). A computer
      program called MZEF is freely available to the genome community and allows users
      to adjust prior probability and to output alternative overlapping exons.

PMID- 9012826
TI  - Characterization of the chicken beta-globin insulator.
AB  - Insulators, first identified in Drosophila, are DNA sequence elements that shield
      a promoter from nearby regulatory elements. We have previously reported that a
      DNA sequence at the 5' end of the chicken beta-globin locus can function as an
      insulator. It is capable of shielding a reporter gene from the activating effects
      of a nearby mouse beta-globin locus control region element in the human
      erythroleukemic cell line K562. In this report, we show that most of the
      insulating activity lies in a 250-bp CpG island (core element), which contains
      the constitutive DNase I-hypersensitive site (5'HS4). DNA binding assays with the
      core sequence reveal a complex protein binding pattern. The insulating activity
      of the core element is multiplied when tandem copies are used. Although CpG
      islands are often associated with promoters of housekeeping genes, we find little
      evidence that the core element is a promoter. Furthermore, the insulator differs
      from a promoter in its ability to block the locus control region effect
      directionally.

PMID- 9012825
TI  - Absence of granulocyte colony-stimulating factor signaling and neutrophil
      development in CCAAT enhancer binding protein alpha-deficient mice.
AB  - Transcription factors are master regulatory switches of differentiation,
      including the development of specific hematopoietic lineages from stem cells.
      Here we show that mice with targeted disruption of the CCAAT enhancer binding
      protein alpha gene (C/EBP alpha) demonstrate a selective block in differentiation
      of neutrophils. Mature neutrophils and eosinophils are not observed in the blood
      or fetal liver of mutant animals, while other hematopoietic lineages, including
      monocytes, are not affected. Instead, most of the white cells in the peripheral
      blood of mutant mice had the appearance of myeloid blasts. We also observed a
      selective loss of expression of a critical gene target of CCAAT enhancer binding
      protein alpha, the granulocyte colony-stimulating factor receptor. As a result,
      multipotential myeloid progenitors from the mutant fetal liver are unable to
      respond to granulocyte colony-stimulating factor signaling, although they are
      capable of forming granulocyte-macrophage and macrophage colonies in
      methylcellulose in response to other growth factors. Finally, we demonstrate that
      the lack of granulocyte development results from a defect intrinsic to the
      hematopoietic system; transplanted fetal liver from mutant mice can reconstitute
      lymphoid but not neutrophilic cells in irradiated recipients. These studies
      suggest a model by which transcription factors can direct the differentiation of
      multipotential precursors through activation of expression of a specific growth
      factor receptor, allowing proliferation and differentiation in response to a
      specific extracellular signal. In addition, the c/ebp alpha -/- mice may be
      useful in understanding the mechanisms involved in acute myelogenous leukemia, in
      which a block in differentiation of myeloid precursors is a key feature of the
      disease.

PMID- 9012827
TI  - Role of the casein kinase I isoform, Hrr25, and the cell cycle-regulatory
      transcription factor, SBF, in the transcriptional response to DNA damage in
      Saccharomyces cerevisiae.
AB  - In the budding yeast, Saccharomyces cerevisiae, DNA damage or ribonucleotide
      depletion causes the transcriptional induction of an array of genes with known or
      putative roles in DNA repair. The ATM-like kinase, Mec1, and the serine/threonine
      protein kinases, Rad53 and Dun1, are required for this transcriptional response.
      In this paper, we provide evidence suggesting that another kinase, Hrr25, is also
      involved in the transcriptional response to DNA damage through its interaction
      with the transcription factor, Swi6. The Swi6 protein interacts with Swi4 to form
      the SBF complex and with Mbp1 to form the MBF complex. SBF and MBF are required
      for the G1-specific expression of G1 cyclins and genes required for S-phase. We
      show that Swi6 associates with and is phosphorylated by Hrr25 in vitro. We find
      that swi4, swi6, and hrr25 mutants, but not mbp1 mutants, are sensitive to
      hydroxyurea and the DNA-damaging agent methyl methane-sulfonate and are defective
      in the transcriptional induction of a subset of DNA damage-inducible genes. Both
      the sensitivity of swi6 mutants to methyl methanesulfonate and hydroxyurea and
      the transcriptional defect of hrr25 mutants are rescued by overexpression of
      SWI4, implicating the SBF complex in the Hrr25/Swi6-dependent response to DNA
      damage.

PMID- 9012829
TI  - UV endonuclease of Micrococcus luteus, a cyclobutane pyrimidine dimer-DNA
      glycosylase/abasic lyase: cloning and characterization of the gene.
AB  - The gene of Micrococcus luteus UV endonuclease (cyclobutane pyrimidine dimer-DNA
      glycosylase/ abasic lyase) was cloned and characterized. The cloned gene, whose
      product had a predicted molecular mass of 17,120 Da, was found to be capable of
      complementing the Escherichia coli uvrA6 mutation in vivo with respect to
      resistance to acetonemediated molecular photosensitization, a treatment producing
      exclusively cyclobutane pyrimidine dimers in DNA. It also generated a nicking
      activity specific for photosensitization-treated DNA by in vitro
      transcription/translation. When expressed in E. coli cells, the gene produced a
      protein structurally identical with UV endonuclease and possessing an activity
      consistent with cyclobutane pyrimidine dimer-DNA glycosylase/abasic lyase with
      respect to the effect of inhibitors and the site of the DNA backbone scission.
      Furthermore, the UV endonuclease-deficient mutant DB7 was shown to regain the
      enzyme through transformation with the cloned gene. The deduced amino acid
      sequence of the gene product was at best 27% identical with that of endonuclease
      V of phage T4, an enzyme strikingly similar to UV endonuclease in molecular and
      catalytic properties. Despite this marginal overall similarity in amino acid
      sequence, four of the seven amino acid residues reported to be functionally
      important in the T4 enzyme were found to be conserved in the M. luteus enzyme. We
      propose that the gene be called uveA.

PMID- 9012828
TI  - Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15
      locus.
AB  - Inheritance of a defect in a neuronal mechanism that regulates response to
      auditory stimuli was studied in nine families with multiple cases of
      schizophrenia. The defect, a decrease in the normal inhibition of the P50
      auditory-evoked response to the second of paired stimuli, is associated with
      attentional disturbances in schizophrenia. Decreased P50 inhibition occurs not
      only in most schizophrenics, but also in many of their nonschizophrenic
      relatives, in a distribution consistent with inherited vulnerability for the
      illness. Neurobiological investigations in both humans and animal models
      indicated that decreased function of the alpha 7-nicotinic cholinergic receptor
      could underlie the physiological defect. In the present study, a genome-wide
      linkage analysis, assuming autosomal dominant transmission, showed that the
      defect is linked [maximum logarithm of the odds (lod) score = 5.3 with zero
      recombination] to a dinucleotide polymorphism at chromosome 15q13-14, the site of
      the alpha 7-nicotinic receptor. Despite many schizophrenics' extremely heavy
      nicotine use, nicotinic receptors were not previously thought to be involved in
      schizophrenia. The linkage data thus provide unique new evidence that the alpha 7
      nicotinic receptor gene may be responsible for the inheritance of a
      pathophysiological aspect of the illness.

PMID- 9012830
TI  - Increased interleukin 12 production in progressive multiple sclerosis: induction
      by activated CD4+ T cells via CD40 ligand.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system postulated to be a cell-mediated autoimmune disease in which interferon
      gamma (IFN-gamma) plays an important role. There is increased IFN-gamma secretion
      in MS, and IFN-gamma administration induces exacerbations of disease. We found
      that interleukin 12 (IL-12) was responsible for raised IFN-gamma secretion in MS
      as anti-IL-12 antibodies reversed raised anti-CD3-induced IFN-gamma in MS
      patients to normal levels. Furthermore, we found a marked increase in T cell
      receptor-mediated IL-12 secretion in progressive MS patients vs. controls (24.8
      +/- 7.7 pg/ml vs. 1.5 +/- 1.0 pg/ml, P = 0.003) and vs. relapsing-remitting
      patients (3.7 +/- 1.4 pg/ml, P < 0.05). Investigation of the cellular basis for
      raised IL-12 demonstrated that T cells from MS patients induced IL-12 secretion
      from non-T cells, and that T cells from MS patients could even drive non-T cells
      from normal subjects to produce increased IL-12. Anti-CD40 ligand antibody
      completely blocked IL-12 secretion induced by activated T cells, and we found
      increased CD40 ligand expression by activated CD4+ T cells in MS patients vs.
      controls. The CD40 ligand-dependent Th1-type immune activation was observed in
      the progressive but not in the relapsing-remitting from of MS, suggesting a link
      to disease pathogenesis and progression and providing a basis for immune
      intervention in the disease.

PMID- 9012831
TI  - BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor
      engagement.
AB  - Bruton's tyrosine kinase (Btk) is essential for B cell activation, but downstream
      targets of Btk have not been defined. We now describe a protein, BAP-135, that is
      associated with Btk in B cells and is a substrate for phosphorylation by Btk. BAP
      135, which exhibits no detectable homology to known proteins, contains six
      occurrences of a hitherto undescribed amino acid repeat and two motifs, similar
      to the Src autophosphorylation site, that represent potential targets for
      tyrosine phosphorylation. The pleckstrin homology domain of Btk comprises the
      principal site of BAP-135 binding. Btk-dependent phosphorylation of BAP-135 is
      abolished by mutations that impair activation of Btk by Src-related kinases. Btk
      and BAP-135 exist in a complex before B cell antigen receptor (BCR) engagement;
      in response to BCR crosslinking, BAP-135 is transiently phosphorylated on
      tyrosine. Taken together, these observations suggest that BAP-135 may reside
      downstream of Btk in a signaling pathway originating at the BCR.

PMID- 9012832
TI  - Correction of the X-linked immunodeficiency phenotype by transgenic expression of
      human Bruton tyrosine kinase under the control of the class II major
      histocompatibility complex Ea locus control region.
AB  - Bruton tyrosine kinase (Btk) is essential for the development of pre-B cells to
      mature B cell stages. Btk-deficient mice manifest an X-linked immunodeficiency
      (xid) defect characterized by a reduction of peripheral IgMlow IgDhigh B cells, a
      lack of peritoneal CD5+ B cells, low serum levels of IgM and IgG3, and impaired
      responses to T cell independent type II (TI-II) antigens. We have generated
      transgenic mice in which expression of the human Btk gene is driven by the murine
      class II major histocompatibility complex Ea gene locus control region, which
      provides gene expression from the pre-B cell stage onwards. When these transgenic
      mice were mated onto a Btk- background, correction of the xid B cell defects was
      observed: B cells differentiated to mature IgMlowIgDhigh stages, peritoneal CD5+
      B cells were present, and serum Ig levels and in vivo responses to TI-II antigens
      were in the normal ranges. A comparable rescue by transgenic Btk expression was
      also observed in heterozygous Btk+/- female mice in those B-lineage cells that
      were Btk-deficient as a result of X chromosome inactivation. These findings
      indicate that the Btk- phenotype in the mouse can be corrected by expression of
      human Btk from the pre-B cell stage onwards.

PMID- 9012834
TI  - Antigen organization regulates cluster formation and induction of cytotoxic T
      lymphocytes by helper T cell subsets.
AB  - Generation of effector cytotoxic T lymphocytes (CTLs) is a process tightly
      governed by regulatory helper T (Th) cells. The nature of cellular interactions
      as well as the precise role of distinct Th cell subsets involved in efficient CTL
      activation remains elusive. Employing in vitro cultures for primary induction of
      human, peptide-specific CTL, a strict requirement for Th cells and linkage of
      epitopes for helper and CTLs on the surface of antigen presenting cells was
      found, suggesting a three cell type cluster as minimal immune regulatory entity.
      Cognate and antigen-driven interactions of T cells were neither essential nor
      sufficient to override the need for linked epitopes. Within the three cell type
      cluster complex, keyhole limpit hemocyanin or tetanus toxoid-reactive Th cells
      promoted generation of MAGE-3- or HIV-gag-specific CTL. Both type 1 and type 2 Th
      cells were recruited and induced by CTL. Interleukin 2 and interferon gamma were
      essential in early stages, and interleukin 4 was utilized in later stages, of CTL
      maturation. Synergistic effects of CD45RA+ and CD45RO+ Th cells were found. The
      data reported here suggest a critical link between the innate and adaptive immune
      system in the initiation process of cytolytic immune responses and offers the
      basis for efficient vaccine strategies.

PMID- 9012833
TI  - Development and function of T cells in T cell antigen receptor/CD3 zeta knockout
      mice reconstituted with Fc epsilon RI gamma.
AB  - Engagement of alpha-beta T cell receptors (TCRs) induces many events in the T
      cells bearing them. The proteins that transduce these signals to the inside of
      cells are the TCR-associated CD3 polypeptides and zeta-zeta or zeta-eta dimers.
      Previous experiments using knockout (KO) mice that lacked zeta (zeta KO) showed
      that zeta is required for good surface expression of TCRs on almost all T cells
      and for normal T cell development. Surprisingly, however, in zeta KO mice, a
      subset of T cells in the gut of both zeta KO and normal mice bore nearly normal
      levels of TCR on its surface. This was because zeta was replaced by the Fc
      epsilon RI gamma (FcR gamma). These cells were relatively nonreactive to stimuli
      via their TCRs. In addition, a previous report showed that zeta replacement by
      the FcR gamma chain also might occur on T cells in mice bearing tumors long term.
      Again, these T cells were nonreactive. To understand the consequences of zeta
      substitution by FcR gamma for T cell development and function in vivo, we
      produced zeta KO mice expressing FcR gamma in all of their T cells (FcR gamma TG
      zeta KO mice). In these mice, TCR expression on immature thymocytes was only
      slightly reduced compared with controls, and thymocyte selection occurred
      normally and gave rise to functional, mature T cells. Therefore, the
      nonreactivity of the FcR gamma + lymphocytes in the gut or in tumor-bearing mice
      must be caused by some other phenomenon. Unexpectedly, the TCR levels of mature T
      cells in FcR gamma TG zeta KO mice were lower than those of controls. This was
      particularly true for the CD4+ T cells. We conclude that FcR gamma can replace
      the functions of zeta in T cell development in vivo but that TCR/CD3 complexes
      associated with FcR gamma rather than zeta are less well expressed on cells.
      Also, these results revealed a difference in the regulation of expression of the
      TCR/CD3 complex on CD4+ and CD8+ T cells.

PMID- 9012835
TI  - Amino-terminal trimming of peptides for presentation on major histocompatibility
      complex class II molecules.
AB  - Major histocompatibility complex (MHC) class II molecules bind antigenic peptides
      for display to T lymphocytes. Although the enzymes involved remain to be
      identified, it is commonly believed that class II associated peptides are
      released from intact antigens through a series of proteolytic steps carried out
      inside antigen presenting cells. We have examined the effect of amino acid
      substitutions on proteolytic processing of the model antigen hen-egg lysozyme
      (HEL). Altered HEL molecules, engineered by site-directed mutagenesis of a HEL
      cDNA, were expressed as separate stable transfectants in a B cell lymphoma line.
      Each transfectant processed a different mutant HEL protein for presentation on
      MHC class II. We purified the resulting class II-associated peptides and analyzed
      them by mass spectrometry. Our results strongly support the hypothesis that
      antigen processing continues after peptide binding to the MHC class II molecule
      and are most consistent with a scenario in which long peptides first bind to MHC
      class II and are then trimmed by exopeptidase.

PMID- 9012836
TI  - Interferon-alpha/beta inhibition of interleukin 12 and interferon-gamma
      production in vitro and endogenously during viral infection.
AB  - Interferon (IFN)-alpha/beta-mediated negative regulation of interleukin 12 (IL
      12) and IFN-gamma proteins is reported here. Both IFN-alpha and IFN-beta
      inhibited fixed Staphylococcus aureus Cowan strain induction of IL-12 and IFN
      gamma production by mouse splenic leukocytes in culture. Extended studies with
      IFN-alpha demonstrated that inhibition was at the level of biologically active IL
      12 p70. Effects were selective, as induction of tumor necrosis factor was
      unaffected and induction of IL-6 was enhanced. Neutralization of IFN-alpha/beta
      expressed endogenously during infections with murine cytomegalovirus (MCMV)
      enhanced early IL-12 and IFN-gamma protein production. Furthermore, during
      infections of mice with lymphocytic choriomeningitis virus (LCMV), this treatment
      revealed a previously undetected early IL-12 and IFN-gamma protein expression,
      and mice deficient in IFN-alpha/beta receptor function, but not control mice,
      also expressed endogenous LCMV-induced IL-12. The effects of IFN-alpha/beta
      neutralization on production of IL-12 and IFN-gamma during the viral infections
      were detected in both serum samples and medium conditioned with splenic
      leukocytes isolated from infected animals. In vitro studies demonstrated that
      splenic leukocytes isolated from LCMV-infected mice were primed to produce IL-12
      in response to stimulation with Staphylococcus aureus Cowan strain, but that this
      responsiveness was sensitive to added IFN-alpha. Moreover, endogenous IFN
      alpha/beta induced by LCMV inhibited in vivo lipopolysaccharide stimulation of IL
      12 production. These results demonstrate a new pathway for regulating cytokine
      responses, and suggest a mechanism for inhibition of IL-12-dependent immune
      responses during viral infections.

PMID- 9012837
TI  - Protection against immunopathological consequences of a viral infection by
      activated but not resting cytotoxic T cells: T cell memory without "memory T
      cells"?
AB  - Immunological memory is a key characteristic of specific immune responses.
      Persistence of increased levels of precursor T cells is antigen-independent and
      is often used as an indicator of T cell memory. This study documents that,
      depending on the chosen readout, cytotoxic T lymphocyte (CTL) memory against
      lymphocytic choriomeningitis virus (LCMV) appears long- or short-lived in the
      absence of persisting antigen. To study T cell memory in the absence of
      persisting antigen, either short-lived antigens were used for immunization or
      adoptive transfer methods were used to eliminate possibly persisting antigen.
      These experiments revealed that increased specific precursor frequencies and CTL
      mediated protection against an i.v. infection with LCMV were long-lived. In
      contrast, CTL-mediated protection against a peripheral infection of the skin with
      LCMV, or of the ovary with recombinant vaccinia virus, was short-lived. These
      results show that maintenance of increased specific CTL precursor frequencies and
      central T cell memory in lymphoid tissue (where preexisting neutralizing
      antibodies usually provide protection anyway) is long-lived and antigen
      independent. In contrast, in protection against peripheral viral infections,
      where the relative kinetics of virus growth and virus elimination by T cells are
      of key importance, T cell memory is short-lived in the absence of antigen. This
      indicates that peripheral T cell memory in antibody-inaccessible tissues is
      mediated by antigen-activated effector T cells and apparently not by specialized
      memory T cells.

PMID- 9012838
TI  - Peripheral deletion of rheumatoid factor B cells after abortive activation by
      IgG.
AB  - Rheumatoid factor (RF) B cells proliferate during secondary immune responses to
      immune complexed antigen and antigen specific T cells, but higher affinity RFs
      are not detected except in patients with rheumatoid arthritis and other
      autoimmune diseases. Consequently, there must exist highly efficient mechanisms
      for inactivation of these higher-affinity RF B cell clones under normal
      circumstances. Exposure of transgenic mice expressing a human IgM RF to soluble
      human IgG in the absence of T cell help causes antigen specific B cell deletion
      in 2-3 days. The deletion is independent of the Fas/Fas ligand (FasL) pathway of
      apoptosis and is preceded by a phase of partial activation involving increase in
      cell size and expression of B7 and ICAM-1, and transient release of low levels of
      immunoglobulin. Complete B cell activation involving the formation of germinal
      centers and sustained high level RF secretion only occurs if T cell help is
      provided simultaneously. RF B cells exposed to tolerogen remain competent to
      secrete RF in vitro if provided with an appropriate antigenic stimulus and T cell
      help. Consequently, death of these cells is not preceded by anergy. Abortive
      activation/deletion of B cells by antigen in the absence of T cell-derived
      survival signals may represent the major mechanism for maintaining peripheral
      tolerance in B cells expressing higher affinity RF. The lack of anergy, and the
      potential for reactivation before death, provide a means for maintaining RF
      production under pathologic circumstances, such as may occur in the inflamed
      rheumatoid synovium.

PMID- 9012839
TI  - Design, synthesis, and in vitro evaluation of cytotoxic analogs of bombesin-like
      peptides containing doxorubicin or its intensely potent derivative, 2
      pyrrolinodoxorubicin.
AB  - Five peptide fragments, based on the C-terminal sequence of bombesin (BN)-(6-14)
      or BN-(7-14), were selected as carriers for radicals doxorubicin (DOX) and 2
      pyrrolino-DOX to create hybrid cytotoxic analogs. All these compounds had a
      reduced peptide bond (CH2-NH or CH2-N) between positions 13 (Phe or Leu) and 14
      (Phe, Leu, or Tac) (Tac = thiazolidine-4-carboxylic acid). Three
      pseudononapeptide carriers contained N-terminal D-Phe or D-Tpi at position 6 (Tpi
      = 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid). Two
      pseudooctapeptides had Gln7 at the N terminus. The conjugation of N-(9
      fluorenylmethoxycarbonyl) doxorubicin (N-Fmoc-DOX)-14-O-hemiglutarate to the
      peptide carriers at the N terminus resulted in cytotoxic hybrids of BN-like
      peptides containing DOX. These hybrids could then be converted to analogs with 2
      pyrrolino-DOX by a reaction with 4-iodobutyraldehyde. The ability of the carriers
      and the conjugates to inhibit the binding of 125I-labeled [Tyr4]BN to receptors
      for BN/gastrin releasing peptide (GRP) on Swiss 3T3 cells was determined.
      Cytotoxic conjugates of pseudooctapeptide carrier analogs displayed the highest
      binding affinity (KD approximately 1 nM). The cytotoxic BN analogs and their
      corresponding cytotoxic radicals exerted similar inhibitory effects on the in
      vitro growth of CFPAC-1 human pancreatic cancer, DMS-53 human lung cancer, PC-3
      human prostate cancer, and MKN-45 human gastric cancer cell lines that have
      receptors for BN/GRP. In DMS-53 cells, the activity of 2-pyrrolino-DOX and its
      conjugates was approximately 2500 times higher than that of DOX and its hybrids.
      These highly potent cytotoxic analogs of BN have been designed as targeted anti
      tumor agents for the treatment of various cancers that possess receptors for
      BN/GRP.

PMID- 9012841
TI  - Constitutive production and thrombin-induced release of vascular endothelial
      growth factor by human megakaryocytes and platelets.
AB  - We have shown that coculture of bone marrow microvascular endothelial cells with
      hematopoietic progenitor cells results in proliferation and differentiation of
      megakaryocytes. In these long-term cultures, bone marrow microvascular
      endothelial cell monolayers maintain their cellular integrity in the absence of
      exogenous endothelial growth factors. Because this interaction may involve
      paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion
      of cytokines, we evaluated megakaryocytic cells for secretion of vascular
      endothelial growth factor (VEGF). Megakaryocytes (CD41a+) were generated by ex
      vivo expansion of hematopoietic progenitor cells with kit-ligand and
      thrombopoietin for 10 days and further purified with immunomagnetic microbeads.
      Using reverse transcription-PCR, we showed that megakaryocytic cell lines (Dami,
      HEL) and purified megakaryocytes expressed mRNA of the three VEGF isoforms (121,
      165, and 189 amino acids). Large quantities of VEGF (> 1 ng/10(6) cells/3 days)
      were detected in the supernatant of Dami cells, ex vivo-generated megakaryocytes,
      and CD41a+ cells isolated from bone marrow. The constitutive secretion of VEGF by
      CD41a+ cells was stimulated by growth factors of the megakaryocytic lineage
      (interleukin 3, thrombopoietin). Western blotting of heparin-Sepharose-enriched
      supernatant mainly detected the isoform VEGF165. In addition,
      immunohistochemistry showed intracytoplasmic VEGF in polyploid megakaryocytes.
      Thrombin stimulation of megakaryocytes and platelets resulted in rapid release of
      VEGF within 30 min. We conclude that human megakaryocytes produce and secrete
      VEGF in an inducible manner. Within the bone marrow microenvironment, VEGF
      secreted by megakaryocytes may contribute to the proliferation of endothelial
      cells. VEGF delivered to sites of vascular injury by activated platelets may
      initiate angiogenesis.

PMID- 9012842
TI  - Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by
      p16INK4a but not by the alternative reading frame protein p19ARF.
AB  - The INK4a gene, one of the most frequently disrupted tumor suppressor loci in
      human cancer, encodes two unrelated proteins, p16INK4a and p19ARF, each of which
      is capable of inducing cell cycle arrest. Splicing of alternative first exons (1
      alpha vs. 1 beta) to a common second exon within INK4a generates mRNAs in which
      exon 2 sequences are translated in two different reading frames. One of the
      products, the cyclin D-dependent kinase inhibitor p16INK4a, is functionally
      inactivated by mutations or deletions in a wide variety of cancers. However,
      because many such mutations reside in exon 2, they also affect the alternative
      reading frame (ARF) protein. To determine whether such mutations disrupt p19ARF
      function, we introduced naturally occurring missense mutations into mouse INK4a
      exon 2 sequences and tested mutant p16INK4a and p19ARF proteins for their ability
      to inhibit cell cycle progression. Six p19ARF point mutants remained fully active
      in mediating cell cycle arrest in NIH 3T3 fibroblasts, whereas two of the
      corresponding mutations within p16INK4a resulted in complete loss of activity.
      Analysis of p19ARF deletion mutants indicated that the unique aminoterminal
      domain encoded by exon 1 beta was both necessary and sufficient for inducing G1
      arrest. Therefore, cancer-associated mutations within exon 2 of the INK4a gene
      specifically target p16INK4a, and not p19ARF, for inactivation.

PMID- 9012840
TI  - Epidermal growth factor receptor activation induces nuclear targeting of
      cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in
      polarizing colon cancer cells.
AB  - Nonsteroidal antiinflammatory drugs reduce the risk of colon cancer, possibly via
      cyclooxygenase (COX) inhibition. The growth factor-inducible COX-2, which is
      overexpressed in neoplastic colonic tissue, is an attractive target to mediate
      this effect. Herein we have exploited the ability of a human colon cancer cell
      line, HCA-7 Colony 29, to polarize when cultured on Transwell (Costar) filters to
      study COX-2 production and the vectorial release of prostaglandins (PGs).
      Administration of type alpha transforming growth factor to the basolateral
      compartment, in which the epidermal growth factor receptor (EGFR) resides,
      results in a marked induction of COX-2 immunoreactivity at the base of the cells
      and the unexpected appearance of COX-2 in the nucleus. The increase in COX-2
      protein is associated with a dose- and time-dependent increase in PG levels in
      the basolateral, but not apical, medium. Amphiregulin is the most abundantly
      expressed EGFR ligand in these cells, and the protein is present at the
      basolateral surface. EGFR blockade reduces baseline COX-2 immunoreactivity, PG
      levels, and mitogenesis in a concentration-dependent manner. Two specific COX-2
      inhibitors, SC-58125 and NS 398, also, in a dose-dependent manner, attenuate
      baseline and type alpha transforming growth factor-stimulated mitogenesis,
      although PG levels are decreased > 90% at all concentrations of inhibitor tested.
      These findings show that activation of the EGFR stimulates COX-2 production and
      its translocation to the nucleus, vectorial release of PGs, and mitogenesis in
      polarized HCA-7 Colony 29 cells.

PMID- 9012843
TI  - Free radical oxidation of brain proteins in accelerated senescence and its
      modulation by N-tert-butyl-alpha-phenylnitrone.
AB  - According to the free radical theory of aging, reactive oxygen species cause
      oxidative damage, proposed to be an underlying factor of the aging process. In
      the current study, we have used electron paramagnetic resonance spin labeling,
      measurements of protein carbonyl content, an index of protein oxidation, and
      determination of the activity of glutamine synthetase (an oxidatively sensitive
      enzyme) to report that cortical synaptosomal membranes from the senescence
      accelerated-prone (SAMP8) mouse showed structural characteristics of free radical
      oxidative stress relative to the senescence accelerated-resistant (SAMR1) mouse.
      The SAMP8 mouse exhibited a decrease in the relevant EPR parameter consistent
      with oxidative stress (P < 0.002), a decreased glutamine synthetase activity (P <
      0.05), and an increased protein carbonyl content (P < 0.01) compared with these
      parameters in the SAMR1 mouse. Further, because free radical trapping compounds
      have been demonstrated to extend maximum life span and improve cognition in SAMP8
      mice, we investigated the protective nature of the known free radical scavenger,
      N-tert-butyl-alpha-phenylnitrone (PBN), on the physical state of cortical
      synaptosomal membrane proteins. For 14 days, SAMR1 and SAMP8 mice were injected
      with 30 mg/kg PBN while the controls were injected with the corresponding volume
      of saline. Characteristic of less oxidized systems, cortical synaptosomal
      membranes from the PBN-injected SAMP8 mouse exhibited a return toward normal
      values of the relevant EPR parameter [the M1 = +1 low-field weakly immobilized
      line/M1 = +1 low-field strongly immobilized line (W/S) ratio of a protein
      specific spin label] (P < 0.001) compared with that from saline-injected SAMP8
      mice. In SAMR1 mice, in contrast to SAMP8, there was no significant change in the
      conformation of membrane proteins or protein carbonyl content of cortical
      synaptosomal membranes from the PBN-injected and saline-injected SAMR1 mice,
      showing that PBN itself did not induce conformational changes in cortical
      synaptosomal membrane proteins. The results are discussed with reference to the
      use of free radical scavengers as potential anti-aging agents.

PMID- 9012844
TI  - Inhibition of the activity of poly(ADP ribose) synthetase reduces ischemia
      reperfusion injury in the heart and skeletal muscle.
AB  - Reperfusion of the ischemic myocardium results in the generation of oxygen
      derived free radicals, NO, and presumably peroxynitrite. These, in turn, may
      cause strand breaks in DNA, which activate the nuclear enzyme poly(ADP ribose)
      synthetase (PARS). This results in a rapid depletion of intracellular NAD and
      ATP. When this reaction is excessive, there is ultimately cell death. Here we
      demonstrate that 3-aminobenzamide (and several other, chemically distinct,
      inhibitors of PARS activity) reduces the infarct size caused by ischemia and
      reperfusion of the heart or skeletal muscle of the rabbit. Inhibition of PARS
      activity also attenuates the myocardial dysfunction caused by global ischemia and
      reperfusion in the isolated, perfused heart of the rabbit. In skeletal muscle,
      inhibition of the activity of neuronal NO synthase reduces infarct size,
      indicating that the formation of NO contributes to the activation of PARS there.
      There is no significant neuronal NO synthase activity in the heart, and hence NO
      synthase inhibitors did not reduce myocardial infarct size. Thus, activation of
      PARS contributes to the cell death caused by ischemia-reperfusion, and PARS
      inhibitors may constitute a novel therapy for ischemia-reperfusion injury.

PMID- 9012845
TI  - Inhibition of tumorigenesis by a cytosine-DNA, methyltransferase, antisense
      oligodeoxynucleotide.
AB  - This paper tests the hypothesis that cytosine DNA methyltransferase (DNA MeTase)
      is a candidate target for anticancer therapy. Several observations have suggested
      recently that hyperactivation of DNA MeTase plays a critical role in initiation
      and progression of cancer and that its up-regulation is a component of the Ras
      oncogenic signaling pathway. We show that a phosphorothioate-modified, antisense
      oligodeoxynucleotide directed against the DNA MeTase mRNA reduces the level of
      DNA MeTase mRNA, inhibits DNA MeTase activity, and inhibits anchorage independent
      growth of Y1 adrenocortical carcinoma cells ex vivo in a dose-dependent manner.
      Injection of DNA MeTase antisense oligodeoxynucleotides i.p. inhibits the growth
      of Y1 tumors in syngeneic LAF1 mice, reduces the level of DNA MeTase, and induces
      demethylation of the adrenocortical-specific gene C21 and its expression in
      tumors in vivo. These results support the hypothesis that an increase in DNA
      MeTase activity is critical for tumorigenesis and is reversible by
      pharmacological inhibition of DNA MeTase.

PMID- 9012846
TI  - A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8,
      inhibits apoptosis but does not heterodimerize with Bax or Bak.
AB  - The Bcl-2 protein family is characterized by the ability to modulate cell death,
      and members of this family share two highly conserved domains called Bcl-2
      homology 1 (BH1) and 2 (BH2) which have been shown to be critical for the death
      repressor activity of Bcl-2 and Bcl-xL. Through sequence analysis we identified a
      novel viral Bcl-2 homolog, designated KSbcl-2, from human herpesvirus 8 (HHV8) or
      Kaposi sarcoma-associated herpesvirus. The overall amino acid sequence identity
      between KSbcl-2 and other Bcl-2 homologs is low (15-20%) but concentrated within
      the BH1 and BH2 regions. Overexpression of KSbcl-2 blocked apoptosis as
      efficiently as Bcl-2, Bcl-xL, or another viral Bcl-2 homolog encoded by Epstein
      Barr virus, BHRF1. Interestingly, KS-bcl-2 neither homodimerizes nor
      heterodimerizes with other Bcl-2 family members, suggesting that KSbcl-2 may have
      evolved to escape any negative regulatory effects of the cellular Bax and Bak
      proteins. Furthermore, the herpesvirus Bcl-2 homologs including KSbcl-2, BHRF1,
      and ORF16 of herpesvirus saimiri contain poorly conserved Bcl-2 homology 3 (BH3)
      domains compared with other mammalian Bcl-2 homologs, implying that BH3 may not
      be essential for anti-apoptotic function. This is consistent with our observation
      that amino acid substitutions within the BH3 domain of Bcl-xL had no effect on
      its death-suppressor activity.

PMID- 9012847
TI  - Quantitative detection of immune activation transcripts as a diagnostic tool in
      kidney transplantation.
AB  - Procedures to diagnose renal allograft rejection depend upon detection of graft
      dysfunction and the presence of a mononuclear leukocytic infiltrate; however, the
      presence of a modest cellular infiltrate is often not conclusive and can be
      detected in non-rejecting grafts. We have pursued a molecular approach utilizing
      reverse transcription (RT)-PCR to test the diagnostic accuracy of multiple immune
      activation gene analysis as means to diagnose renal allograft rejection. The
      magnitude of intragraft gene expression of 15 immune activation genes was
      quantified by competitive RT-PCR in 60 renal allograft core biopsies obtained for
      surveillance or to diagnose the etiology of graft dysfunction. Results were
      compared with a clinicopathological analysis based upon the histological
      diagnosis (Banff criteria) and the response to antirejection treatment. During
      acute renal allograft rejection intragraft expression of the interleukin (IL)-7
      (P < 0.001), IL-10 (P < 0.0001), IL-15 (P < 0.0001), Fas ligand (P < 0.0001),
      perforin (P < 0.0001), and granzyme B (P < 0.0015), but not IL-2, interferon
      gamma, or IL-4, genes is significantly heightened. Amplified RANTES and IL-8 gene
      transcripts are sensitive but nonspecific markers of rejection. A simultaneous RT
      PCR evaluation of perforin, granzyme B, and Fas ligand identifies acute
      rejection, including cases with mild infiltration, with extraordinary sensitivity
      (100%) and specificity (100%). Effective antirejection therapy results in a rapid
      down-regulation of gene expression. The combined analysis of Fas ligand,
      perforin, and granzyme B gene expression by quantitative RT-PCR provides a
      reliable tool for diagnosis and follow-up of acute renal allograft rejection. Its
      accuracy and a potential rapid application within few hours suggest its use in
      the clinical management of renal transplant patients.

PMID- 9012848
TI  - Diverse tumorigenesis associated with aberrant development in mice overexpressing
      hepatocyte growth factor/scatter factor.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived,
      multifunctional paracrine regulator possessing mitogenic, motogenic, and
      morphogenetic activities in cultured epithelial cells containing its tyrosine
      kinase receptor, Met. c-met has been implicated in oncogenesis through
      correlation of expression with malignant phenotype in specific cell lines and
      tumors. Paradoxically, however, HGF/SF can also inhibit the growth of some tumor
      cells. To elucidate the oncogenic role of HGF/SF in vivo, transgenic mice were
      created such that HGF/SF was inappropriately targeted to a variety of tissues.
      HGF/SF transgenic mice developed a remarkably broad array of histologically
      distinct tumors of both mesenchymal and epithelial origin. Many neoplasms arose
      from tissues exhibiting abnormal development, including the mammary gland,
      skeletal muscle, and melanocytes, suggesting a functional link between mechanisms
      regulating morphogenesis and those promoting tumorigenesis. Most neoplasms,
      especially melanomas, demonstrated overexpression of both the HGF/SF transgene
      and endogenous c-met, and had enhanced Met kinase activity, strongly suggesting
      that autocrine signaling broadly promotes tumorigenesis. Thus, subversion of
      normal mesenchymal-epithelial paracrine regulation through the forced
      misdirection of HGF/SF expression induces aberrant morphogenesis and subsequent
      malignant transformation of cells of diverse origin.

PMID- 9012849
TI  - Identification of a structural constituent and one possible site of postembryonic
      formation of a teleost otolithic membrane.
AB  - A gelatinous otolithic membrane (OM) couples a single calcified otolith to the
      sensory epithelium in the bluegill sunfish (Lepomis macrochirus) saccule, one of
      the otolithic organs in the inner ear. Though the OM is an integral part of the
      anatomic network of endorgan structures that result in vestibular function in the
      inner ear, the identity of the proteins that make up this sensory accessory
      membrane in teleosts, or in any vertebrate, is not fully known. Previously, we
      identified a cDNA from the sunfish saccular otolithic organ that encoded a new
      member of the collagen family of structural proteins. In this study, we examined
      biochemical features and the localization of the saccular collagen (SC) protein
      in vivo using polyclonal antisera that recognize the noncollagenous domains of
      the SC protein. The SC protein, in vivo, was identified as a 95-kDa glycoprotein
      in sunfish whole-saccule lysate and in homogenates of microdissected saccular
      OMs. Immunohistochemical analyses demonstrated that the SC protein was localized
      within one of the two distinct layers of the sunfish saccular OM. The SC protein
      was also detected within the cytoplasm of supporting cells at the edges of the
      saccular sensory epithelium, indicating that these cells are a primary site for
      the synthesis of this structural protein. Further studies of the organization of
      this matrix molecule in the OM may help clarify the role of this sensory
      accessory membrane in vestibular sensory function.

PMID- 9012850
TI  - Molecular characterization of two mammalian bHLH-PAS domain proteins selectively
      expressed in the central nervous system.
AB  - Here we describe two mammalian transcription factors selectively expressed in the
      central nervous system. Both proteins, neuronal PAS domain protein (NPAS) 1 and
      NPAS2, are members of the basic helix-loop-helix-PAS family of transcription
      factors. cDNAs encoding mouse and human forms of NPAS1 and NPAS2 have been
      isolated and sequenced. RNA blotting assays demonstrated the selective presence
      of NPAS1 and NPAS2 mRNAs in brain and spinal cord tissues of adult mice. NPAS1
      mRNA was first detected at embryonic day 15 of mouse development, shortly after
      early organogenesis of the brain. NPAS2 mRNA was first detected during early
      postnatal development of the mouse brain. In situ hybridization assays using
      brain tissue of postnatal mice revealed an exclusively neuronal pattern of
      expression for NPAS1 and NPAS2 mRNAs. The human NPAS1 gene was mapped to
      chromosome 19q13.2-q13.3, and the mouse Npas1 gene to chromosome 7 at 2
      centimorgans. Similarly, the human NPAS2 gene was assigned to chromosome 2p11.2
      2q13, and the mouse Npas2 gene to chromosome 1 at 21-22 centimorgans. The
      chromosomal regions to which human NPAS1 and NPAS2 map are syntenic with those
      containing the mouse Npas1 and Npas2 genes, indicating that the mouse and human
      genes are true homologs.

PMID- 9012851
TI  - The neural code between neocortical pyramidal neurons depends on neurotransmitter
      release probability.
AB  - Although signaling between neurons is central to the functioning of the brain, we
      still do not understand how the code used in signaling depends on the properties
      of synaptic transmission. Theoretical analysis combined with patch clamp
      recordings from pairs of neocortical pyramidal neurons revealed that the rate of
      synaptic depression, which depends on the probability of neurotransmitter
      release, dictates the extent to which firing rate and temporal coherence of
      action potentials within a presynaptic population are signaled to the
      postsynaptic neuron. The postsynaptic response primarily reflects rates of firing
      when depression is slow and temporal coherence when depression is fast. A wide
      range of rates of synaptic depression between different pairs of pyramidal
      neurons was found, suggesting that the relative contribution of rate and temporal
      signals varies along a continuum. We conclude that by setting the rate of
      synaptic depression, release probability is an important factor in determining
      the neural code.

PMID- 9012852
TI  - Dendritic calcium conductances generate high-frequency oscillation in
      thalamocortical neurons.
AB  - Cortical-projecting thalamic neurons, in guinea pig brain slices, display high
      frequency membrane potential oscillations (20-80 Hz), when their somata are
      depolarized beyond -45 mV. These oscillations, preferentially located at
      dendritic sites, are supported by the activation of P/Q type calcium channels, as
      opposed to the expected persistent sodium conductance responsible for such
      rhythmic behavior in other central neurons. Short hyperpolarizing pulses reset
      the phase and transiently increase the amplitude of these oscillations. This
      intrinsic thalamic electroresponsiveness may serve as a cellular-based temporal
      binding mechanism that sharpens the temporal coincidence of cortical-feedback
      synaptic inputs, known to distribute at remote dendritic sites on thalamic
      neurons.

PMID- 9012853
TI  - Expression and regulation of the neuropeptide Y Y2 receptor in sensory and
      autonomic ganglia.
AB  - The Y2 subtype of neuropeptide tyrosine (NPY) receptors (Y2R) and some
      neuropeptides have been studied with in situ hybridization in sensory and
      autonomic neurons of rat and monkey. Between 10% and 20% of the lumbar dorsal
      root ganglion (DRG) neuron profiles (NPs) contain Y2R mRNA in the rat and monkey.
      In rat DRGs Y2R mRNA is expressed in calcitonin gene-related peptide (CGRP)
      positive, medium-sized, and large neurons, that is in a complementary fashion to
      the Y1R that is located in small CGRP neurons. In monkey DRGs Y2R mRNA is
      expressed mainly in small neurons. Peripheral axotomy up-regulates the Y2R in
      small and large DRG neurons in both species. Y2R and NPY mRNAs are colocalized in
      many large neurons in axotomized rat DRGs. Y2R mRNA is expressed in 50% of the
      NPs in the nodose ganglion with a modest increase after axotomy. Y2R mRNA is
      detected in a few NPs in normal rat superior cervical ganglia, with a marked
      increase after transection of the carotid nerves. No Y2R mRNA-positive, but many
      (approximately 30%) weakly Y1R mRNA-positive NPs were found in the sphenopalatine
      ganglion. Finally, Y2R mRNA levels increase in rat spinal motoneurons after
      axotomy. Thus, under normal circumstances NPY may act on Y1 and Y2Rs expressed,
      respectively, in small and large CGRP-positive DRG neurons in the rat. Y2R may be
      an important receptor in the viscero-sensory neurons. Y2Rs may be particularly
      important after axotomy serving as presynaptic and/or autoreceptors on rat DRG,
      superior cervical ganglion, and nodose ganglion neurons and as presynaptic
      receptors in monkey DRG neurons.

PMID- 9012854
TI  - On the relationship between synaptic input and spike output jitter in individual
      neurons.
AB  - What is the relationship between the temporal jitter in the arrival times of
      individual synaptic inputs to a neuron and the resultant jitter in its output
      spike? We report that the rise time of firing rates of cells in striate and
      extrastriate visual cortex in the macaque monkey remain equally sharp at
      different stages of processing. Furthermore, as observed by others, multiunit
      recordings from single units in the primate frontal lobe reveal a strong peak in
      their cross-correlation in the 10-150 msec range with very small temporal jitter
      (on the order of 1 msec). We explain these results using numerical models to
      study the relationship between the temporal jitter in excitatory and inhibitory
      synaptic input and the variability in the spike output timing in integrate-and
      fire units and in a biophysically and anatomically detailed model of a cortical
      pyramidal cell. We conclude that under physiological circumstances, the standard
      deviation in the output jitter is linearly related to the standard deviation in
      the input jitter, with a constant of less than one. Thus, the timing jitter in
      successive layers of such neurons will converge to a small value dictated by the
      jitter in axonal propagation times.

PMID- 9012855
TI  - Regulation of microtubule dynamics by the neuronal growth-associated protein
      SCG10.
AB  - Dynamic assembly and disassembly of microtubules is essential for cell division,
      cell movements, and intracellular transport. In the developing nervous system,
      microtubule dynamics play a fundamental role during neurite outgrowth,
      elongation, and branching, but the molecular mechanisms involved are unknown.
      SCG10 is a neuron-specific protein that is membrane-associated and highly
      enriched in growth cones. Here we show that SCG10 binds to microtubules, inhibits
      their assembly, and can induce microtubule disassembly. We also show that SCG10
      overexpression enhances neurite outgrowth in a stably transfected neuronal cell
      line. These data identify SCG10 as a key regulator of neurite extension through
      regulation of microtubule instability.

PMID- 9012856
TI  - Inhibition of nuclear factor kappa B by prostaglandin A1: an effect associated
      with heat shock transcription factor activation.
AB  - Prostaglandins (PGs) function as intracellular signal mediators in the regulation
      of a variety of physiological and pathological processes, including inflammation
      and immune responses. Cyclopentenone PGs are characterized by antiviral activity
      against several viruses, including human immunodeficiency virus type 1 (HIV-1),
      and by the ability to induce heat shock protein expression through activation of
      the heat shock transcription factor. Here we report that PGA1 is a potent
      inhibitor of nuclear factor-kappa B (NF-kappa B) activation in human cells and of
      NF-kappa B-dependent HIV-1 transcription in long terminal repeat-chloramphenicol
      acetyl-transferase transient transfection experiments. PGA1 acts by inhibiting
      phosphorylation and preventing degradation of the NF-kappa B inhibitor I kappa B
      alpha. Inhibition does not require protein synthesis, is dependent on the
      presence of a reactive cyclopentenonic moiety, and is associated with heat shock
      transcription factor activation. Because NF-kappa B is critically involved in the
      activation of immunoregulatory and viral genes, inhibition of its activity could
      be a major component of the immunosuppressive and antiviral activity of PGs.

PMID- 9012857
TI  - Selective reconstitution of gastrin-releasing peptide receptor with G alpha q.
AB  - Identification of the molecular mechanisms that determine specificity of coupling
      interactions between gastrin-releasing peptide receptors (GRPrs) and their
      cognate heterotrimeric GTP-binding proteins is a fundamental step in
      understanding the signal transduction cascade initiated by receptor-ligand
      interaction. To explore these mechanisms in greater detail, we have developed an
      in situ reconstitution assay in chaotrope-extracted membranes from mouse
      fibroblasts expressing the GRPr, and we have used it to measure GRPr-catalyzed
      binding of GTP gamma S to purified G protein alpha subunits. Binding studies with
      125I-labeled [D-Tyr6]bombesin(6-13) methyl ester (125I-Tyr-ME), a GRPr specific
      antagonist, show a single binding site with a Kd = 1.4 nM +/- 0.4 (mean +/- SD, n
      = 3) and capacity of 15-22 pmol of receptor per mg of protein in the extracted
      membrane preparations, representing a 2- to 3-fold enrichment of binding sites
      compared with the membranes before extraction. Quantitative ligand displacement
      analysis using various unlabeled GRPr agonists shows a rank order of potency
      characteristic of the GRPr: bombesin > or = GRP > > neuromedin B. Reconstitution
      of urea extracted membranes with a purified G alpha q showed that receptor
      catalyzed binding of GTP gamma S was dependent on agonist (GRP) and G beta gamma
      subunits. The EC50 for GRP was 3.5 nM, which correlates well with the reported Kd
      of 3.1 nM for GRP binding to GRPr expressed in mouse fibroblasts [Benya, R. V.,
      et al. (1994) Mol. Pharmacol. 46, 235-245]. The apparent Kd for bovine brain G
      beta gamma in this assay was 60 nM, and the Km for squid retinal G alpha q was 90
      nM. The GRPr-catalyzed binding of GTP gamma S is selective for G alpha q, since
      we did not detect receptor-catalyzed exchange using either G alpha i/o or G alpha
      t. These data demonstrate that GRPr can functionally couple to G alpha q but not
      to the pertussis toxin-sensitive G alpha i/o or retinal specific G alpha t. This
      in situ receptor reconstitution method will allow molecular characterization of G
      protein coupling to other heptahelical receptors.

PMID- 9012858
TI  - Failure to express the P-selectin gene or P-selectin blockade confers early
      pulmonary protection after lung ischemia or transplantation.
AB  - Endothelial P-selectin expression contributes to the first wave of neutrophil
      (polymorphonuclear leukocyte: PMN) influx in several inflammatory conditions.
      Although remote tissue ischemia, such as a crush injury to the hindlimb, may
      result in P-selectin-mediated pulmonary leukosequestration, it is not known
      whether the lungs exhibit a similar response after hypothermic preservation or
      when subjected to a direct ischemic insult. To determine if P-selectin may
      mediate early primary graft failure, left lungs harvested from male Lewis rats
      were preserved for 6 hr at 4 degrees C and transplanted orthotopically into
      isogeneic recipients. Recipients immunodepleted of PMNs before transplantation
      demonstrated improved graft function; pulmonary vascular resistance was reduced
      approximately 6-fold, arterial oxygenation was increased approximately 3-fold,
      and recipient survival was increased approximately 4-fold (P < 0.05, 0.05, and
      0.005, respectively). Administration of a blocking anti-P-selectin IgG 10 min
      before reperfusion diminished graft PMN infiltration and resulted in improved
      graft function and recipient survival compared with controls. To establish the
      role of P-selectin in normothermic pulmonary ischemia, mice were subjected to
      temporary left pulmonary artery ligation. After functional removal of the
      nonischemic right lung, mice deletionally mutant for the P-selectin gene (P
      selectin-/-) exhibited reduced PMN infiltration (approximately 2-fold), improved
      arterial oxygenation (approximately 2-fold), and improved survival (approximately
      3-fold) compared with P-selectin +/+ control mice (P < 0.05, 0.01, and 0.05,
      respectively). These studies isolate and identify the central role of a single
      gene product (P-selectin) in early PMN recruitment and tissue injury after frank
      pulmonary ischemia and in the setting of lung transplantation after hypothermic
      preservation.

PMID- 9012859
TI  - A homolog of the mammalian GTPase Rab2 is present in Arabidopsis and is expressed
      predominantly in pollen grains and seedlings.
AB  - Vesicle traffic between the endoplasmic reticulum and the Golgi apparatus in
      mammals requires the small GTP-binding protein Rab2, but Saccharomyces cerevisiae
      appears not to have a Rab2 homolog. Here it is shown that the higher plant,
      Arabidopsis thaliana, contains a gene, At-RAB2, whose predicted product shares
      79% identity with human Rab2 protein. Transgenic plants containing fusions
      between beta-glucuronidase and sequences upstream of At-RAB2 demonstrated
      histochemical staining predominantly in maturing pollen and rapidly growing
      organs of germinating seedlings. beta-glucuronidase activity in pollen is first
      detectable at microspore mitosis and increases thereafter. In this respect, the
      promoter of At-RAB2 behaves like those of class II pollen-specific genes, whose
      products are often required after germination for pollen tube growth. Seedling
      germination and pollen tube growth are notable for their unusually high rates of
      cell wall and membrane biosynthesis. These results are consistent with a role for
      At-RAB2 in secretory activity.

PMID- 9012860
TI  - Synthesis and characterization of composite nucleic acids containing 2', 5'
      oligoriboadenylate linked to antisense DNA.
AB  - Composite nucleic acids, known as 2-5A antisense chimeras, cause the 2-5A
      dependent ribonuclease (RNase L) to catalyze the specific cleavage of RNA in cell
      free systems and in intact cells. Such 2-5A antisense chimeras are 5'
      monophosphorylated, 2,'5'-linked oligoadenylates covalently attached to antisense
      3',5'-oligodeoxyribonucleotides by means of a linker containing two residues of
      1,4-butanediol phosphate. Here we report a fully automated synthesis of 2-5A
      antisense chimeras on a solid support using phosphoramidite methodology with
      specific coupling time modifications and their subsequent purification by reverse
      phase ion-pair and anion exchange HPLC. Purified 2-5A antisense chimeras were
      characterized by [1H]NMR and [31P]NMR, MALDIMS, and capillary gel
      electrophoresis. The synthetic 2',5'-linked oligoadenylate showed no
      phosphodiester isomerization to 3',5' during or after synthesis. In addition, we
      have developed facile methodologies to characterize the chimeras using digestion
      with various hydrolytic enzymes including snake venom phosphodiesterase I and
      nuclease P1. Finally, Maxam-Gilbert chemical sequencing protocols have been
      developed to confirm the entire sequence of these chimeric oligonucleotides.

PMID- 9012862
TI  - Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation.
AB  - Oligomers possessing the Morpholino phosphorodiamidate backbone were evaluated
      for resistance to a variety of enzymes and biologic fluids. A 25-mer was
      incubated with nucleases, proteases, esterases, and serum, and the reaction
      mixtures were directly analyzed by MALDI-TOF mass spectrometry. The 25-mer was
      completely resistant to 13 different hydrolases and serum and plasma. The
      excellent resistance of Morpholino phosphorodiamidates to enzymatic attack
      indicates their suitability for in vivo use.

PMID- 9012861
TI  - Random sequence phosphorothioate oligonucleotides evoke dramatic phenotypic
      alterations in cardiac myocyte cultures.
AB  - Cardiac myocytes displayed modest and uncoordinated contractile activity
      regardless of whether they are cultured in the presence or absence of unmodified
      random sequence oligonucleotides (oligos), as expected. Much to our surprise,
      however, when cardiac myocytes were cultured in the presence of random sequence
      phosphorothioate (PS) oligos, they reorganized into cablelike aggregates and
      displayed surging and coordinated contractile activity. Consistent with these
      observations, photobleaching experiments revealed that gap junction conductivity
      between affected cardiac myocytes was enhanced fourfold relative to control
      cultures. Furthermore, whereas atrial natriuretic factor (ANF) gene expression
      was induced in control cultures relative to intact hearts, this aberrant
      expression was selectively repressed in response to PS oligos. As PS oligos
      appear to mitigate deleterious effects that result from the proteolytic dispersal
      or culturing of cardiac myocytes or both, we suggest that these may useful cell
      culture reagents. It is interesting to contemplate whether cardiac myocytes might
      also be responsive to PS oligos within intact hearts, as this issue has potential
      clinical significance.

PMID- 9012863
TI  - Inhibition of human collagenase activity by antisense oligonucleoside
      methylphosphonates.
AB  - Oligodeoxyribonucleoside methylphosphonates (d-OMP) were synthesized whose
      sequences are complementary to sequences found in the mRNA coding for the 72-kDa
      (MMP-2) or 92-kDA (MMP-9) forms of human collagenase i.v., matrix
      metalloproteinases (MMP) whose excessive secretion correlates with the metastatic
      potential of tumor cells. The effects of these oligomers on MMP-2 and MMP-9
      activities secreted by HT1080 cells, a human fibrosarcoma cell line, were studied
      using a gelatin zymography assay. A d-OMP, M2.3, complementary to nucleotides 14
      to 28 of the initiation codon region of MMP-2 mRNA selectively inhibited MMP-2
      activity, whereas a d-OMP, M9.1, which was targeted to nucleotides -19 to -5 of
      the 5'-untranslated region of MMP-9 mRNA selectively inhibited MMP-9 activity
      over the concentration range 5-50 microM. At 100 microM concentration, both M2.3
      and M9.1 inhibited the activities of both MMP-2 and MMP-9. These oligomers were
      completely stable under cell culture conditions and did not appear to adversely
      affect cell growth after 48 hours at concentrations up to 100 microM, although
      100 microM M9.1 did reduce cell growth 30% after prolonged, 120-hours exposure.
      Other d-OMP tested either had no effect on collagenase activity or inhibited both
      MMP-2 and MMP-9 activities. The latter oligomer was complementary to MMP-2 mRNA
      and partially complementary to MMP-9 mRNA. Oligomer M2.3 was also tested for its
      effects on the morphology of malignant human lung cells, BZR-T33, growing on the
      surface of reconstituted base membrane, Matrigel, in culture. In absence of
      oligomer, the BZR-T33 cells formed extensive networks indicative of the ability
      of the cells to invade the Matrigel substrate. In the presence of 100 microM
      M2.3, BZR-T33 formed colonies of rounded cells, a morphology typical of
      noninvasive cells. Other non-complementary d-OMP had no effect on the morphology
      of BZR-T33 under these conditions. These results suggest that antisense d-OMP may
      be useful for inhibiting expression of collagenase in human tumor cells and for
      studying the role of collagenase expression in tumor cell metastasis.

PMID- 9012864
TI  - Polydeoxyguanine motifs in a 12-mer phosphorothioate oligodeoxynucleotide augment
      binding to the v3 loop of HIV-1 gp120 and potency of HIV-1 inhibition
      independency of G-tetrad formation.
AB  - Phosphorothioate oligodeoxynucleotides belong to a class of polyanions that bind
      to the third variable domain (v3) of HIV-1 gp120 and inhibit infectivity of a
      wide variety of HIV-1 isolates. This potent v3 binding of phosphorothioate
      oligodeoxynucleotides, which is relatively independent of the nucleotide sequence
      of the oligodeoxynucleotides, decreases with chain length (below 18-mers) and is
      low for 8-mers. However, recent studies have observed a nucleotide sequence
      dependent augmentation of phosphorothioate oligodeoxynucleotide binding to v3 for
      8-mers that contain the S-dG4 motif (e.g., SdT2G4T2) and have suggested that
      formation of quadruple helical tetraplexes (G-tetrads) is associated with the
      acquisition of v3 binding ability by small phosphorothioate
      oligodeoxynucleotides. In the current study, a series of SdG4-containing
      oligodeoxynucleotides were synthesized with varying tandem length (including the
      8-mer SdT2G4T2, the 12-mer SdG4T4G4, and the 28-mer SdG4(T4G4)3) and compared
      with phosphorothioate oligodeoxynucleotides (with similar lengths or related
      sequences) for (1) their inhibition of the binding of mAb 9284, which binds to
      the N-terminal portion of the v3 loop, (2) the values of Kc when these compounds
      are used as competitors of the rgp120-binding of an alkylating phosphodiester
      oligodeoxynucleotide probe, and (3) inhibition of HIV-1 infectivity in a cell
      cell transmission model. The presence of S-dG4 motifs and the number of tandem
      motifs augmented v3 binding and anti-HIV-1 infectivity for small (8-mer or 12-mer
      oligodeoxynucleotides) but did not significantly augment the potency of 28-mers.
      Whereas tetraplex formation of SdT2G4T2 may contribute to its v3 binding, the 12
      mer SdG4T4G4 does not migrate as the tetraplex on nonreducing gels, suggesting
      that S-dG4 motifs may augment anti-HIV activity by multiple mechanisms.

PMID- 9012865
TI  - Specific suppression of human tumor necrosis factor-alpha synthesis by antisense
      oligodeoxynucleotides.
AB  - Recent clinical studies using neutralizing antibodies point to a key role for
      tumor necrosis factor-alpha (TNF-alpha) in chronic inflammatory diseases.
      Antisense technique is a recent approach aiming at inhibition of single proteins.
      Previously, we described nonspecific induction of TNF by phosphorothioate
      oligonucleotides. In this study, we established an in vitro model that allows
      specific inhibition of TNF synthesis, bypassing TNF induction. Freshly isolated
      human monocytes were incubated with oligonucleotides and the cationic lipid
      lipofectin in different ratios. TNF synthesis was stimulated with
      lipopolysaccharide and quantified by a specific radioimmunoassay (RIA). Among all
      sequences tested, one of the antisense oligonucleotides complementary to the
      translation initiation region of TNF mRNA (5'-CAT GCT TTC AGT CAT-3') revealed
      highest efficacy. At 2 microM, the antisense oligonucleotide inhibited TNF
      synthesis by up to 79%. A concentration as low as 250 nM of the antisense
      oligonucleotide was effective. Scrambled controls and controls with different,
      defined degrees of mismatches confirmed a sequence-specific action. Examination
      with confocal fluorescence microscopy showed a marked difference comparing
      lipofectin-mediated vs. spontaneous uptake. This study defines criteria that from
      the prerequisite necessary for design and application of antisense
      oligonucleotides against TNF in vivo.

PMID- 9012866
TI  - Comparison of the antiviral efficacy of ribozymes and antisense RNA directed
      against bovine leukemia virus rex/tax.
AB  - Despite the theoretical attraction of ribozymes, which cleave their target RNA,
      as compared with antisense RNA, which only blocks translation, few studies have
      assessed the relative efficacy of ribozymes and antisense RNA directed against
      the identical target sequence. Previously, we described the efficacy of a
      hammerhead ribozyme targeted against rex/tax, a regulatory gene of bovine
      leukemia virus (BLV). In this study, we asked whether antisense RNA targeted
      against the same site would also be efficacious. BLV-infected bat lung cells were
      transfected with an antisense RNA-encoding plasmid under the control of sarcoma
      virus (RSV) promoter, and stable cell lines were selected. No inhibition of viral
      p24 expression was demonstrated in seven cell lines transfected with the
      antisense RNA targeted at the same site as the ribozyme or in three cell lines
      transfected with an antisense sequence targeted against the tax 5' initiation
      codon. Although in previous experiments antisense DNA oligonucleotides inhibited
      Tax expression in vitro, stably transfected plasmids encoding antisense RNA of
      the same sequence did not inhibit viral expression in BLV-infected cells in this
      study. These results suggest that in persistently infected cells producing high
      levels of BLV, the ribozyme is more effective than antisense RNA directed at
      rex/tax transcripts.

PMID- 9012867
TI  - Application of a dicistronic mRNA expression vector to antisense RNA expression
      in mammalian cells.
AB  - One important role of antisense RNA expression in mammalian cell biology is to
      partially suppress the functions of target genes of which the functions are
      unknown but which are indispensable for host cell growth. Therefore, we applied a
      dicistronic mRNA expression vector to express antisense p53 RNA in mouse
      fibrosarcoma MethA cells. We also established several clones in which the p53
      gene functions were partially suppressed by the introduced antisense RNA.
      Compared with the control MethA clones, the contents of p53 protein in those
      expressing the antisense RNA were about halved, and their growth rates were
      remarkably decreased. These results proved that an antisense RNA in a dicistronic
      mRNA construct decreases the cellular content of a targeted gene product and that
      clones harboring the dicistronic mRNA construct can be established in which
      expression levels of the introduced antisense RNA are controlled by the
      stringency of drug selection.

PMID- 9012869
TI  - To be effective health care providers and patient advocates, we must keep the
      public's trust.

PMID- 9012870
TI  - Surgical masks.

PMID- 9012871
TI  - Age-specific competencies.

PMID- 9012872
TI  - The RN first assistant's role during inferior epigastric artery harvesting.
AB  - At the Cleveland Clinic Foundation, RN first assistants (RNFAs) have replaced
      inexperienced interns and rotating general surgery residents as surgical first
      assistants. Their new role includes harvesting inferior epigastric arteries
      (IEAs) for coronary artery bypass procedures. The RNFAs remove the IEAs through
      paramedian incisions that extend from below the umbilicus to the groin, dissect
      the IEAs as pedicles, and complete wound closure. This is one example of the
      expanded role of RNFAs during complex surgical procedures.

PMID- 9012873
TI  - Implementation of the RN first assistant role.
AB  - The RN first assistant (RNFA) program at Children's Hospital of The King's
      Daughters in Norfolk, Va, began as a dream in which RNs could expand their role
      within a cost-effective, hospital-based implementation of the RNFA role. Our
      dream included a career development path for perioperative nurses who had few
      other career options within the surgical arena. This article describes how the
      dream came true.

PMID- 9012874
TI  - RN first assistants increase access to quality surgical care in a rural setting.

PMID- 9012875
TI  - Transoral resection of spinal cord tumors and posterior cervical spine
      stabilization.
AB  - Transoral resection of an anterior spinal cord tumor consists of three major
      phases: corpectomy (i.e., removal of vertebral bodies), tumor resection, and
      duraplasty (i.e., repair of the dura mater). A second surgical procedure,
      posterior stabilization of the occiput to the C3 vertebra, consists of an iliac
      crest bone graft for cervical spine fusion and the application of a rigid
      fixation device. This article describes a patient who underwent a transoral
      resection of an extramedullary intradural tumor at the C2-C3 level of the spinal
      cord and a posterior cervical spine stabilization procedure. Perioperative
      nursing concerns and interventions are discussed from the standpoint of the
      patient's physical and mental postoperative recovery.

PMID- 9012876
TI  - Fallopian tube anastomosis procedures to restore fertility.
AB  - Fallopian tube interruption is a common form of contraception in the United
      States. A significant portion of women who undergo these procedures are in their
      twenties and thirties. For a variety of reasons (eg, change in marital status,
      wish for additional children, death of children, religious concerns,
      psychological factors), many of these women later seek restoration of fertility
      through tubal anastomosis procedures. Using microsurgical techniques with
      minilaparotomy or laparoscopy procedures, surgeons are able to restore fallopian
      tube patency in many women. Positive surgical outcomes depend on the method of
      fallopian tube interruption, the type of tubal anastomosis performed, and the
      length of the fallopian tube segments being anastomosed.

PMID- 9012877
TI  - The perioperative nurse's role in assisted-fertility procedures.
AB  - Infertility is the inability to achieve pregnancy within a stipulated period of
      time (ie, one year) or the repeated failure to carry a pregnancy to term.
      Advances in assistive reproductive technology have enabled many couples to
      overcome infertility, but health care providers need to remember that these
      couples require much support. This article addresses the perioperative nurse's
      responsibilities during assisted-fertility procedures that are performed in the
      OR (eg, transvaginal oocyte retrieval, gamete intrafallopian transfer, zygote
      intrafallopian transfer.

PMID- 9012878
TI  - Implementing an informatics system in a perioperative environment.
AB  - This article identifies and describes strategies for successful implementation of
      an informatics system in a perioperative environment. With the trend toward
      managed care, perioperative nurses must address the challenge of instituting
      advanced technology in organizations with limited staffing and other resources.
      Planning methods of the past no longer are relevant in today's health care
      systems; therefore, innovative planning approaches are important. Five key
      elements in implementation of an informatics system are: a collaborative planning
      process, education and involvement of staff members regarding the systems design,
      development of a timetable, selection of a focus group, and assessment of staff
      members' training requirements. Methods are described for using a focus group
      process, including recommendations for structuring the focus group and
      establishing responsibilities of core group members.

PMID- 9012879
TI  - The prevalence of perioperative nurse clinical judgments.
AB  - A clinical judgement about a patient situation precedes the selection of
      appropriate nursing actions and the identification of patient outcomes. The North
      American Nursing Diagnosis Association nomenclature (i.e., nursing diagnoses) is
      the accepted language for naming nurse's clinical judgements. Two hundred thirty
      nine members of the Association of Operating Room Nurses, Inc, rated the
      frequency and treatment priority of 60 nursing diagnoses. They rated two
      diagnostic labels (i.e., risk for perioperative positioning injury, risk for
      infections occurring in more than 50% of the clinical judgments they make about
      perioperative patient situations that require immediate nursing action. These
      data reinforce perioperative nurses' primary role in protecting surgical patients
      from harm.

PMID- 9012880
TI  - Timing of perioperative antibiotic administration.

PMID- 9012882
TI  - Clinical exemplar demonstrates patient advocacy role of perioperative nurses
      employed in industry.

PMID- 9012881
TI  - Research-based practice provides for foundation for perioperative nursing's
      preferred future.

PMID- 9012883
TI  - Standards of perioperative administrative practice. Association of Operating Room
      Nurses.

PMID- 9012884
TI  - Recommended practices for the care and cleaning of surgical instruments and
      powered equipment. Association of Operating Room Nurses.

PMID- 9012885
TI  - Recommended practices for managing the patient receiving conscious
      sedation/analgesia. Association of Operating Room Nurses.

PMID- 9012886
TI  - Delegation of patient care responsibilities to unlicensed assistive personnel.

PMID- 9012895
TI  - Medical gas and water: new frontier for artificial organ technologies.

PMID- 9012896
TI  - What is functional water?

PMID- 9012897
TI  - Nitric oxide and the lung: an overview.
AB  - This brief discussion focuses on the effects of nitric oxide (NO) in the lung. A
      short introduction of some of the physical characteristics of the NO gas molecule
      and the endogenous production of NO by the vascular endothelium is addressed
      first. This is followed by a review of inhaled NO use as a bronchodilator of the
      airway and recent findings of the endogenous production of NO during positive end
      expiratory pressure and the possible role of NO produced in the paranasal
      sinuses. Next, the use of inhaled NO for both pulmonary hypertension and
      improvement in oxygenation under a variety of clinical situations is discussed.
      Finally, some suggestions are given regarding the safe delivery of inhaled NO
      during clinical applications using a face mask, an anesthesia circuit, and a
      mechanical ventilator.

PMID- 9012898
TI  - Inhaled low-dose nitric oxide for postoperative care in patients with congenital
      heart defects.
AB  - Postoperative pulmonary hypertensive crisis is a major problem that may account
      for a substantial part of the postoperative mortality and morbidity. We,
      therefore, evaluated the effect of inhalation of low-dose nitric oxide (NO) on
      postoperative care in pediatric patients with pulmonary hypertension. We studied
      10 infants and children ages 1-108 months (median age, 11 months) with congenital
      heart disease associated with pulmonary hypertension. The NO and N2 gas mixture
      was then mixed with varied quantities of air and oxygen and delivered into a
      respirator instead of an inspiratory tube. Patients were treated with inhaled NO
      for 38.6 +/- 19.6 h (range 1-200 h). All patients were eventually weaned from
      high level sedation and respirator. The NO concentration ranged from 2 to 5 parts
      per million. During NO inhalation patients demonstrated a statistically
      significant reduction in systolic pulmonary arterial pressure by approximately
      26%; from 55 +/- 10 to 41 +/- 20 mm Hg. Inhalation of NO resulted in a
      significant increase of Pao2 from 110 +/- 16 to 149 +/- 29 mm Hg. A-aDo2
      significantly decreased from 284 +/- 27 to 247 +/- 31 mm Hg. In conclusion, we
      have shown that a low-dose NO inhalation acted as pulmonary vasodilator in
      patients with preexisting pulmonary hypertension.

PMID- 9012899
TI  - Effect of nitric oxide on oxygenation and hemodynamics in infants after cardiac
      surgery.
AB  - We evaluated the effect of nitric oxide (NO) on infants after congenital cardiac
      surgery. Inhaled NO was administered to 7 infants after congenital cardiac
      surgery. Inhaled NO concentration ranged from 2.5 to 10 parts per million (ppm).
      The respiratory index (RI = A-aDO2/PaO2) decreased from 7.4 +/- 2.5 to 4.7 +/-
      3.1 in the right RI group (RI > or = 3, n = 4) 30 min after NO inhalation. After
      discontinuation of NO inhalation, RI increased to the preinhalation level. NO
      inhalation was restarted in 2 patients in the high RI group because of severe
      worsening of oxygenation. RI was not affected by starting or discontinuing of NO
      in the low RI group (RI < 3, n = 3). Systemic blood pressure did not
      significantly change in the 2 groups. Pulmonary arterial pressure (PAP) was
      measured in 4 patients, and it decreased by 21, 10, and 10%, respectively, 30 min
      after NO inhalation in 3 patients, but did not change in the remaining patient.
      After discontinuation of NO inhalation, PAP increased in all patients, and in 2
      cases, PAP was higher than baseline value. NO inhalation is effective in
      improving oxygenation in infants with a high RI after cardiac surgery. However,
      careful monitoring of the respiratory and hemodynamic states is required after
      discontinuing NO inhalation.

PMID- 9012900
TI  - Effects of inhaled nitric oxide on postoperative pulmonary circulation in
      patients with congenital heart disease.
AB  - We studied 22 patients with residual pulmonary hypertension or symptoms of
      postoperative pulmonary hypertensive crisis. They received low-dose inhalation
      (10 ppm) of nitric oxide (NO), a selective pulmonary vasodilator, after total
      correction for congenital heart anomalies. Fifteen minutes of NO inhalation
      improved the pulmonary circulation and lessened the imbalance in the ventilation
      perfusion ratio in both groups. Thus, NO inhalation is effective in the treatment
      of pulmonary hypertension and in the prevention of pulmonary hypertensive crises
      after total correction for congenital heart anomalies. All patients continued to
      receive NO therapeutically. The duration of such therapeutic NO inhalation was
      well correlated with postoperative Qp/Qs (p = 0.014) and Rp/Rs (p = 0.029).

PMID- 9012901
TI  - Long-term sedation with isoflurane in postoperative intensive care in cardiac
      surgery.
AB  - After cardiac surgery, patients often require prolonged mechanical ventilation.
      We studied the effectiveness and potential toxicity of isoflurane sedation in 40
      patients undergoing mechanical ventilation after cardiovascular surgery. All
      patients who received isoflurane (0.5-1.0 minimum alveolar concentration [MAC]
      were well sedated by it without significant adverse effects, such as renal,
      hepatic, or cardiovascular dysfunction. The highest serum inorganic fluoride
      concentration recorded was 45 mumol/L after 98 MAC h. Patients on isoflurane
      recovered more rapidly and were weaned from mechanical ventilation sooner than
      those sedated with intravenous drugs including fentanyl/midazolam. Patients who
      received intravenous sedatives, but not those on isoflurane, often showed
      tachyphylaxis in the early stages, and some exhibited an abstinence syndrome
      involving nonpurposeful movements. Patients sedated with isoflurane did not show
      these two side effects. In conclusion, isoflurane can provide effective long-term
      sedation for patients after cardiovascular surgery without significant adverse
      effects.

PMID- 9012902
TI  - Helium/oxygen breathing improves hypoxemia after cardiac surgery.
AB  - The effects of helium/oxygen (He/O2) on oxygenation (respiratory index
      [PaO2/FiO2] and intrapulmonary shunt [Qs/Qt]) and on lung parameters (dynamic
      compliance [Cdyn] and peak inspiratory pressure [PIP]) were studied in 12
      patients. After cardiac surgery, they had impairment of oxygenation without
      physiological findings and with normal chest radiographs despite having a
      positive end expiratory pressure of up to 10 cm H2O. After 90 min of inhalation
      of He/O2, oxygenation had improved significantly; that is, PaO2/FidO2 increased
      significantly (from 113 to 174 mm Hg; mean values are given; p < 0.01), and there
      was a significant fall in Qs/Qt (from 29 to 19%; p < 0.001) together with an
      increase in Cdyn (from 60 ml/cm H2O to 64 ml/cm H2O; p < 0.05). These results
      suggest that He/O2 may have improved oxygenation by recruiting previously
      obstructed small airways and alveoli.

PMID- 9012903
TI  - Trial of electrolyzed strong acid aqueous solution lavage in the treatment of
      peritonitis and intraperitoneal abscess.
AB  - Electrolyzed strong acid aqueous solution is acidic water that contains active
      oxygen and active chlorine and possesses a redox potential. We performed
      peritoneal and abscess lavages with an electrolyzed strong acid aqueous solution
      to treat 7 patients with peritonitis and intraperitoneal abscesses, who were seen
      in our department between December 1994 and April 1995. The underlying disease
      was duodenal ulcer perforation in 4 of these 7 patients and gastric ulcer
      perforation, acute enteritis, and intraperitoneal perforation of pyometrium in 1
      patient each. Irrigation was performed twice a day. Microbiological studies of
      the paracentesis fluid were negative in 3 cases, and the irrigation period was 2
      4 days. Anaerobic bacteria were isolated in 3 of the 4 positive cases
      (Bacteroides in 2, Prevotella in 1), and a fungus (Candida) was isolated in the
      remaining patient. The period of irrigation in these patients ranged from 9 to 12
      days, but conversion to a microorganism negative state was observed in 3-7 days.

PMID- 9012904
TI  - Treatment of infectious skin defects or ulcers with electrolyzed strong acid
      aqueous solution.
AB  - A chronic ulcer with an infection such as methicillin-resistant Staphylococcus
      aureus is hard to heal. Plastic and reconstructive surgeons often encounter such
      chronic ulcers that are resistant to surgical or various conservative treatments.
      We applied conservative treatment using an electrolyzed strong acid aqueous
      solution and obtained satisfactory results. The lesion was washed with the
      solution or soaked in a bowl of the solution for approximately 20 min twice a
      day. Fresh electrolyzed strong acid aqueous solution is unstable and should be
      stored in a cool, dark site in a sealed bottle. It should be used within a week
      after it has been produced. Here we report on 15 cases of infectious ulcers that
      were treated by electrolyzed strong acid aqueous solution. Of these cases, 7
      patients were healed, 3 were granulated, and in 5, infection subsided. In most
      cases the lesion became less reddish and less edematous. Discharge or foul odor
      from the lesion was decreased. Electrolyzed strong acid aqueous solution was
      especially effective for treating a chronic refractory ulcer combined with
      diabetes melitus or peripheral circulatory insufficiency. This clinically applied
      therapy of electrolyzed strong acid aqueous solution was found to be effective so
      that this new therapeutic technique for ulcer treatment can now be conveniently
      utilized.

PMID- 9012905
TI  - Successful treatment of mediastinitis after cardiovascular surgery using
      electrolyzed strong acid aqueous solution.
AB  - Dilute povidone-iodine solution has been widely used as an irrigant for the
      treatment of mediastinitis. However, its use is not without adverse effects and
      often causes poor growth of granulation tissues. To avoid the problems seen with
      the use of povidone-iodine solution, we applied electrolyzed strong acid aqueous
      solution (ESAAS) to mediastinal irrigation in 4 patients (2 infants and 2 adults)
      who developed mediastinitis after cardiovascular surgery. According to the "open"
      method, the mediastinal wound was left open and irrigated with ESAAS 1 to 3 times
      a day until the infection was eradicated. Satisfactory growth of granulation
      tissues was observed in all patients treated with no evidence of adverse effects
      attributable to ESAAS. Delayed primary sternum closure was performed for 2
      patients, and musculocutaneous transposition of rectus abdominis for 1. Our
      experience suggests that irrigation with ESAAS is a safe and effective method of
      therapy for mediastinitis.

PMID- 9012906
TI  - The physiological property and function of the electrolyzed-ionized calcium
      Aquamax on water molecular clusters fractionization.
AB  - Aquamax, the ionized mineral (Ca, 21 mg/ml; MG, 0.068 mg/ml; Na 0.13 mg/ml; K,
      0.006 mg/ml) is a fermented organic mineral extract. The fundamental
      physiological property and function of this mineral is to promote the molecular
      level mineral supply to the cell inside. The contained minerals exist at a
      molecular level to fractionize the molecular clusters of water and to make
      water's penetration ratio into objects higher only at 0.1-0.2% concentration.
      Existing minerals, especially the calcium, were barely dissolved in water, and
      its low penetration was caused by its low electrolyzed behavior plus the effects
      from an anion mineral, such as phosphorous, sulfur, nitrogen, or any oxalic acid
      combining with a colloidal calcium to construct and crystallize as the calcium
      phosphate and the calcium sulfate. Aquamax minerals penetrate into objects to
      fractionize water molecular clusters and to make water functional, neutralize in
      the anion mineral and oxalic acid elements, raise the object's electric
      conductivity, and preserve perishables.

PMID- 9012907
TI  - Fixation of various porcine arteries with an epoxy compound.
AB  - The clinical results of biological vascular grafts have been unsatisfactory. The
      poor results of these vascular grafts may be attributed to the fixatives,
      aldehydes, used in fixing tissues. In an attempt to overcome this problem, a new
      fixative, epoxy compound, has recently been used to fix biological vascular
      grafts. The study was undertaken to investigate the crosslinking characteristics,
      fixation index and denaturation temperature, of various porcine arteries fixed
      with an epoxy compound. The porcine arteries investigated in the study were the
      common carotid artery, internal thoracic artery, abdominal aorta, and saphenous
      artery. In addition, the effects of sonication on the porcine arteries before
      fixation on their crosslinking characteristics were analyzed. The fresh and
      glutaraldehyde-fixed arteries were used as controls. It was noted that glycine,
      proline, and alanine were the most abundant amino acids found in the porcine
      internal thoracic artery. In the amino acid analysis, it was observed that the
      amino acids in the porcine arteries reacted with epoxy compound or glutaraldehyde
      were lysine, hydroxylysine, histidine, and arginine. Of these amino acids, lysine
      was the most reactive. In general, the fixed arteries were relatively stiffer
      than their fresh counterparts. The fixation indices and denaturation temperatures
      of various porcine arteries were comparable throughout the entire fixation
      process. The amounts of free amino groups of the sonicated arteries were
      significantly lower than those of their unsonicated counterparts (p < 0.05). It
      is speculated that the diminishing free amino groups of the sonicated arteries
      may be attributed to the removal of the destroyed cell debris and adherent
      proteins of the arteries after sonication. However, it was learned that
      sonication on the porcine arteries before fixation did not seem to affect their
      fixation indices and denaturation temperatures. The results obtained in this
      study may help one in selecting the raw materials for developing a small-diameter
      biological vascular graft

PMID- 9012908
TI  - Mechanism and computer simulation of a new robot hand for potential use as an
      artificial hand.
AB  - A prosthetic hand is essential to provide rehabilitation for individuals who lose
      a hand. A prosthetic hand serves two purposes: cosmetic and functional. In this
      paper, a prototype of the artificial hand with an emphasis on the functionality
      purpose is presented. A new mechanism, the NTU-Hand (NTU-Hand, patent number
      107115, Taiwan, R.O.C.), which has 5 fingers with 17 degrees of freedom, has been
      designed and fabricated in our laboratory. Due to the special design of the
      mechanism, the hand has an uncoupled configuration in which each finger and joint
      are all individually driven. The size of the hand is almost the same as a human
      hand. All actuators, mechanical parts, and sensors are on the hand. The compact
      design makes it feasible to adapt the hand to the injured wrist. A computer
      simulation with three-dimensional graphics was also built to evaluate the
      manipulative range of the artificial hand. From the results of this simulation,
      the relationship between the hand and the grasped object in a specific viewpoint
      can be obtained.

PMID- 9012909
TI  - Priming of anesthesia circuit with xenon for closed circuit anesthesia.
AB  - Xenon is an inert gas with a practical anesthetic potency (1 MAC = 71%). Because
      it is very expensive, the use of closed circuit anesthesia technique is ideal for
      the conduction of xenon anesthesia. Here we describe our methods of starting
      closed circuit anesthesia without excessive waste of xenon gas. We induce
      anesthesia with intravenous agents, and after endotracheal intubation,
      denitrogenate the patient for approximately 30 min with a high flow of oxygen.
      This is done to minimize accumulation of nitrogen in the anesthesia circuit
      during the subsequent closed-circuit anesthesia with xenon. Anesthesia is
      maintained with an inhalational anesthetic during this period. Then, we
      discontinue the inhalation agent and start xenon. For this transition, we feel it
      is unacceptable to simply administer xenon at a high flow until the desired end
      tidal concentration is reached because it is too costly. Instead we set up
      another machine with its circuit filled in advance (i.e., primed) with at least
      60% xenon in oxygen and switch the patient to this machine. To prime the circuit,
      we push xenon using a large syringe into a circuit, which was prefilled with
      oxygen. Oxygen inside the circuit is pushed out before it is mixed with xenon,
      and xenon waste will thus be minimized. In this way, we can achieve close to 1
      MAC from the beginning of xenon anesthesia, and thereby minimize the risk of
      light anesthesia and awareness during transition from denitrogenation to closed
      circuit xenon anesthesia.

PMID- 9012910
TI  - Development of an intravascular pumping oxygenator using a new silicone membrane.
AB  - A new intravascular pumping oxygenator (IVPO) was developed for intravascular gas
      exchange and circulatory assistance in critically ill patients with respiratory
      and circulatory failure. The IVPO utilizes new silicone hollow fibers (diameter,
      1 mm; membrane width, 50 microns) and consists of two driving tubes for the
      oxygenation and pumping of circulating blood. The performance characteristics of
      the IVPO were studied using an experiment ex vivo model. With a mean hemoglobin
      concentration of 10.5 +/- 2.3 g/dl, total oxygen transfer was 5.6 +/- 1.5 ml/min
      at a blood flow of 200 ml/min and 6.3 +/- 2.2 ml/min at a blood flow of 250
      ml/min. Total CO2 transfer was 3.8 +/- 1.4 ml/min at a blood flow of 200 ml/min
      and 4.2 +/- 1.6 ml/min at a blood flow of 250 ml/min. Blood flow increased to a
      maximum of 250 ml/min during IVPO pumping. This preliminary experiment
      demonstrated that the IVPO has the capacity to function both as circulatory
      assist pump and as an intravascular hollow fiber oxygenator.

PMID- 9012911
TI  - Hydraulic assessment of the floating impeller phenomena in a centrifugal pump.
AB  - A compact eccentric inlet port centrifugal blood pump (C1E3) has been perfected
      for a long-term centrifugal ventricular assist device as well as a
      cardiopulmonary bypass pump. The C1E3 pump incorporates a sealless design and a
      blood stagnation free structure. The pump's impeller is magnetically coupled to
      the driver magnet in a sealless manner. The latest hemolysis study reveals that
      hemolysis is affected by the magnetic coupling distance between the driver and
      impeller magnet. Furthermore, a floating phenomenon can be observed in a pivot
      bearing supported pump. Attention was focused on the relationship between the
      floating phenomenon's characteristics and the magnetic coupling design in the
      C1E3 pump. Studies were conducted to evaluate the hydromechanical performance in
      the floating phenomenon. In this study, the relationship between the magnetic
      coupling design and the floating phenomenon was verified with a smooth spinning
      condition. The optimized magnetic coupling distance for the floating mode was
      estimated to be 12 mm for left ventricular assist device and 9 mm for
      cardiopulmonary bypass pump. Obtaining an optimal spinning condition is required
      for regulating the magnetic coupling force. To develop a double pivot bearing
      pump, it is necessary to establish an optimal spinning and/or floating condition
      and to determine the proper magnetic coupling and magnetic force between the
      impeller and driver.

PMID- 9012912
TI  - Nitric oxide (NO) inhalation.

PMID- 9012913
TI  - Physiologic control of cardiac assist devices.

PMID- 9012915
TI  - Potential hazards of deionization systems used for water purification in
      hemodialysis.

PMID- 9012916
TI  - The role of the leech in medical therapeutics.
AB  - Leeching is considered by many to be a discredited medical relic of the past.
      This view is not justified, since leeches still play an important part in modern
      medicine, as in microsurgery and in the treatment of patients with post-phlebitic
      syndrome. Hirudin, the potent thrombin inhibitor of leech saliva, has been cloned
      and is used in the treatment of cardiological and hematological disorders. In our
      search for other antihemostatic factors in Hirudo medicinalis saliva, we found
      inhibitors of platelet aggregation induced by thrombin, collagen, adenosine 5'
      diphosphate, epinephrine, platelet-activating factor and arachidonic acid. We
      purified apyrase (adenosine 5'-triphosphate diphosphohydrolase), which is a non
      specific inhibitor of platelet aggregation by virtue of its action on adenosine
      5'-diphosphate. We isolated and characterized the platelet-activating factor
      antagonist and also identified and recovered an inhibitor of coagulation factor
      Xa from leech saliva. This report summarizes our findings and those of other
      investigators, as well as the experience of one of us (A.E.) in leech therapy.

PMID- 9012917
TI  - Consensus Conference on unrelated donor bone-marrow transplantation. Royal
      College of Physicians of Edinburgh, 29-30 October 1996.

PMID- 9012918
TI  - The history of bone-marrow transplantation.

PMID- 9012919
TI  - Unrelated bone-marrow transplantation in adults.

PMID- 9012920
TI  - The role of unrelated bone-marrow transplantation in childhood acute leukaemia.
AB  - Early reports would suggest that closely matched UD BMT is an adequate substitute
      for MSD BMT in children with relapsed ALL. Protagonists of BMT might suggest that
      UD BMT be used in the absence of a MSD in all cases of BM relapse of ALL.
      However, recent improvements in chemoradiotherapy schedules have reduced the
      benefits of BMT in terms of overall survival, particularly in children with a
      long first remission, and a more sensible approach would be to advocate UD BMT in
      early relapsing aggressive disease, prospectively compare UD BMT to chemotherapy
      in less aggressive disease, and not utilize UD BMT for low-risk disease. The best
      prognostic indicators for relapsing disease depend on the site of relapse and
      duration of first remission. Recommendations for the use of UD BMT in children
      with relapsed ALL based on these criteria are given in Table 1.

PMID- 9012921
TI  - Adoptive immunotherapy post bone-marrow transplantation.

PMID- 9012922
TI  - Major histocompatibility complex class II deficiency: a clinical review.
AB  - Major histocompatibility complex Class II deficiency or bare lymphocyte syndrome
      is a rare combined immunodeficiency that accounts for 5% of all cases of severe
      combined immunodeficiency. The syndrome is characterized by a lack of human
      leucocyte antigen Class II gene expression, absence of cellular and humoral T
      cell immune response to foreign antigens, and impaired antibody productions,
      resulting in extreme susceptibility to viral, bacterial and fungal infections. In
      some patients, there is a reduced cell surface expression of human leucocyte
      antigen Class I molecules also. Major histocompatibility complex Class II
      deficiency is an autosomal recessive disease, most frequent in the Mediterranean
      area. The disease is caused by impaired gene regulation involving trans-acting
      proteins. Somatic cell genetics using cell fusion experiments identified four
      complementation groups, all resulting in the same clinical manifestation. Two
      regulatory genes have been identified so far: Class II trans activator and
      regulatory factor X5. Supportive treatment includes intravenous gammaglobulin and
      prophylaxis against Pneumocystis carinii. The only curative treatment is bone
      marrow transplantation.

PMID- 9012923
TI  - DNA methylation: biology and significance.
AB  - The modification of DNA by cytosine methylation is crucial for normal
      development. DNA methylation patterns are distinctive between tissues and are
      maintained with high fidelity during cell division. DNA methylation probably
      exerts its effects through alterations in chromatin structure, with a resultant
      effect on genetic transcription. 5-methylcytosine is also prone to spontaneous
      hydrolytic deamination to thymine. Whilst most G:T mismatches so produced are
      repaired, failure of mismatch repair leads to established mutation. Indeed,
      mutations that are the result of 5-methylcytosine transitions account for a
      disproportionate number of genetic mutations described in malignant and non
      malignant disease. There is also evidence for substantial deregulation of DNA
      methylation in malignancy. Whether this deregulation is crucial for the
      transformation process, or simply an epiphenomenon associated with it, is still
      not established.

PMID- 9012924
TI  - High-dose chemotherapy with autologous stem cell transplantation is feasible and
      safe in a regional hospital. A 6-year experience in southern Switzerland.
AB  - High-dose therapy with bone marrow (BM) or blood stem cell (BSC) support is a
      high-technology technique usually administered in specialized tertiary centers.
      The use of BSC has made this technique simpler and accessible also to smaller
      hospitals. We retrospectively analyzed the data of patients with lymphoma,
      leukemia and other tumors who received high-dose therapy and BM or BSC
      transplantation in our district hospital, looking at the type of procedure
      performed, complications, use of growth factors, and progression-free and overall
      survival. A total of 40 patients were transplanted over 6 years. No procedure
      related deaths and no permanent organ toxicities were seen. The use of BSC
      brought about a great reduction in the duration of hospital stay, septic
      complications and transfusion of blood components. For patients with lymphoma (n
      = 20) the probabilities of progression-free survival and of overall survival at 2
      years are 48% (95% C.I. 28-68%) and 68% (95% C.I. 46-84%), respectively. Based on
      these data, we believe that ABMT and BSC transplantation are feasible and safe in
      a peripheral hospital when the appropriate human and technical conditions are
      present. Treatment outcome is then comparable to that of specialized centers.

PMID- 9012925
TI  - Allogeneic peripheral blood stem cell transplantation for haematological
      malignancies--an analysis of kinetics of engraftment and GVHD risk.
AB  - We have carried out an analysis of 44 patients undergoing allogeneic PBSC
      transplants from fully HLA-matched related donors with particular emphasis on
      engraftment kinetics and the incidence and severity of GVHD. The recipients had a
      median age of 37 years (range 5-56 years), 16 patients had standard-risk disease
      and 28 had poor-risk disease. GVHD prophylaxis was with cyclosporin A and
      methotrexate (n = 41), cyclosporin A alone (n = 2) or cyclosporin A and methyl
      prednisolone (n = 1). Stem cells were mobilised using G-CSF, collecting a median
      of 5.75 x 10(6) CD34+ cells/kg recipient weight (range 0.94-35 x 10(6) CD34+
      cells/kg). Engraftment times to a neutrophil count > 0.5 x 10(9)/1 and platelets
      > 20 x 10(9)/1 were achieved at a median of day +14 (range 10-25) and day +14
      (range 9-130) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg
      had significantly accelerated neutrophil and platelet engraftment and this number
      of CD34+ cells would appear to be a prerequisite for maximum engraftment using
      PBSC. Acute GVHD occurred in 25 of 43 evaluable patients although in only 12 was
      this clinically significant (grades II-IV). Chronic GVHD has occurred in 17 out
      of 36 evaluable patients, there was no significant difference between the
      standard- and poor-risk groups in incidence of either acute or chronic GVHD. In
      conclusion, these results confirm the feasibility of using PBSC for allogeneic
      transplantation without evidence for increased risk of either acute or chronic
      GVHD and provide further evidence supporting the potential of PBSC to replace
      bone marrow as the major source of haemopoietic cells for allogeneic
      transplantation.

PMID- 9012926
TI  - Lenograstim administration to HLA-identical donor-recipient pairs to accelerate
      marrow recovery post-transplant.
AB  - In an attempt to accelerate marrow recovery after HLA-identical sibling bone
      marrow transplantation, the donors of 12 patients with haematological malignancy
      were given recombinant human granulocyte colony-stimulating factor (rHuG-CSF;
      lenograstim; Granocyte) 5 micrograms/kg/day for seven doses prior to marrow
      harvest. All 12 recipients also received lenograstim 5 micrograms/kg/day from the
      day of transplant until their neutrophil count was 1.0 x 10(9)/1. In addition to
      lenograstim post-transplant and lenograstim-stimulated donor bone marrow the
      first six recipients also received donor peripheral blood stem cells that had
      been enriched for CD34+ stem/progenitor cells and T cell depleted on an immune
      absorption column (cohort 1). The second six patients (cohort 2) received
      lenograstim post-transplant and lenograstim-stimulated donor marrow only. All 12
      patients showed a marked elevation of their circulating white blood cell count
      (predominantly neutrophils) on day 1 post-transplant. Compared to carefully
      matched historical control patients the rate of neutrophil engraftment was
      significantly accelerated in both patient cohorts and platelet engraftment was
      accelerated in cohort 2.

PMID- 9012927
TI  - Multicyclic, dose-intensive chemotherapy supported by hemopoietic progenitors in
      refractory myeloma patients.
AB  - Attempts to increase dose intensity have been hampered by hematologic toxicity.
      To address this issue, we designed a study to determine whether the reinfusion of
      PBPC significantly reduces the toxicity of multicyclic dose-intensive
      chemotherapy. Thirty refractory patients, median age 63, received CY 3 g/m2 plus
      melphalan 60 mg/m2 followed by PBPC and G-CSF (CM regimen). CY (at day 0) and G
      CSF were used to mobilize PBPC harvested by a single leukapheresis at day 10.
      Melphalan was infused at day 11. PBPC were kept unprocessed at 4 degrees C for 48
      h and reinfused at day 12. This regimen was repeated three times every 6 months.
      Outcomes were compared with those of 30 similar patients treated with melphalan
      30 mg/m2 followed by G-CSF only, and repeated every 2 months for a total of six
      cycles. In patients receiving CY plus melphalan followed by PBPC reinfusion, the
      median duration of neutropenia (ANC < 500/microliters) and thrombocytopenia
      (platelets < 2500 microliters) was only 5 and 2 days respectively, and did not
      increase after the subsequent courses. Hematologic toxicity was quite similar to
      that observed after melphalan 30 mg/m2 plus G-CSF. The CM regimen was followed by
      30% complete remission and 86% response > 50%, melphalan 30 mg/m2 by no complete
      remissions and 38% response > 50%. Patients receiving CM regimen showed a longer
      progression-free survival (22 vs 10 months, P < 0.01). The dose intensity of
      melphalan can be doubled by reinfusing PBPC without increasing toxicity. The
      combination of CY and melphalan followed by PBPC improves response rate and
      outcome when compared to low-dose melphalan.

PMID- 9012928
TI  - Peripheral blood stem cell transplantation for relapsed or refractory aggressive
      lymphoma in patients over 60 years of age.
AB  - Intensive chemotherapy with autologous bone marrow transplantation is now
      considered the treatment of choice for young patients with sensitive relapse of
      non-Hodgkin's lymphoma (NHL) but results of this procedure in older patients
      remain unknown. We evaluated the feasibility of two cycles of salvage therapy
      followed by an autologous peripheral blood stem cell (PBSC) transplantation in 13
      patients aged more than 60 years (median age: 62; range 61-72) suffering from
      relapsed (n = 10) or refractory (n = 3) aggressive NHL. All patients had
      previously received first-line treatment containing doxorubicin. An association
      of ifosfamide, VP16, cytosine-arabinoside with or without high-dose methotrexate
      was used as salvage and priming therapy prior to collection of PBSC. All patients
      received G-CSF following salvage therapy. PBSC collection could be performed in
      10 patients and yielded a median number of CFU-GM: 98.4 x 10(4)/kg (range 68
      369). Nine patients underwent a transplantation using BEAM conditioning regimen.
      The median time to granulocyte and platelet recovery was 13 days (range
      respectively: 9-25 and 9-16). One patient died from sepsis after transplantation.
      The main adverse experience occurring after transplantation was a prolonged
      decline of performance status. Seven patients achieved a complete remission and
      one failed to respond. Three patients are still alive in CR. We conclude that
      PBSC collection was possible in selected patients over 60 years of age with
      refractory or relapsed aggressive NHL and myeloablative therapy could be used
      with tolerable toxicity. Hematologic recovery and organ toxicity appears to be
      similar to those observed in younger patients. Deterioration of performance
      status after transplantation is the most important factor that could limit this
      procedure. Further investigations are necessary to determine which patients will
      be able to benefit by this procedure in terms of survival and quality of life.

PMID- 9012929
TI  - Comparison of cytomegalovirus antigenemia and shell vial culture in allogeneic
      marrow transplantation recipients receiving ganciclovir prophylaxis.
AB  - We prospectively monitored 61 allogeneic BMT patients for evidence of CMV
      infection and disease starting 7 days prior to transplant until day 110 after
      transplant. Patients receiving pre- and post-transplantation ganciclovir
      prophylaxis were followed for the incidence of infection by the CMV antigenemia
      assay and shell vial cultures. The median age of all patients was 32 years (range
      5-54 years). Fourteen (25%) of 57 evaluable patients became CMV antigenemia or
      culture positive. The incidence of culture or antigenemia positivity in CMV
      seropositive or seronegative patients with a seropositive donor was 29% (14 of 49
      patients). The antigenemia assay became positive a median of 29 days (range 12-89
      days) after BMT as compared to 46 days (range 26-98 days) by shell vial assay (P
      < 0.001). There were no cases of CMV disease in the first 110 days after
      transplant. This study demonstrates that despite the use of prophylactic
      ganciclovir, BMT patients developed CMV infection but did not progress to disease
      in this study, the CMV antigenemia assay may be used to monitor for CMV infection
      during prophylaxis, and the current regimens for CMV prophylaxis with ganciclovir
      may require further evaluation to determine an optimal regimen to prevent CMV
      infection.

PMID- 9012930
TI  - Successful program to prevent aspergillus infections in children undergoing
      marrow transplantation: use of nasal amphotericin.
AB  - Aspergillus infections in the pediatric bone marrow transplant (BMT) patients are
      usually fatal. We began the use of a prophylactic nasal spray of amphotericin in
      1990. This nasal spray was provided in addition to low-dose intravenous
      amphotericin. During the time of this study, the number of fatal cases of
      aspergillus in the pediatric BMT population was reduced significantly from 13.8%
      to 1.8% (P < 0.0025) thereby suggesting that the use of nasal amphotericin in
      this population helps to prevent fatal aspergillus infections. The lack of
      significant side-effects and the ease of administration make this a very helpful
      preventive measure in the supportive care of pediatric bone marrow transplant
      patients.

PMID- 9012931
TI  - Risk of cytomegalovirus infection after peripheral blood stem cell
      transplantation.
AB  - From 1992 to 1995, 105 patients received PBSCT in our hospitals and we observed
      no incidence of CMV-pneumonia. To clarify whether activation of CMV occurs in
      these patients shell vial cultures, CMV antigenemia and PCR (DNA-PCR and RT-PCR)
      were used as detection methods for CMV. Bronchoalveolar lavage (BAL) samples, MNC
      and PMN samples from peripheral blood leukocytes, and urine samples were taken
      from 17 patients on day 35 after PBSCT. CMV was detected in one urine specimen
      but not detected in any of the BAL, MNC or PMN specimens by shell vial culture.
      CMV antigenemia provided no positive data. Nine of the 74 samples taken from the
      17 patients proved positive by DNA-PCR, but all CMV-mRNA results were negative by
      RT-PCR. We performed CMV antigenemia and PCR on MNC and PMN specimens from six
      patients every 1 to 2 weeks after transplantation to determine whether and when
      CMV was activated. Two patients tested positive transiently by DNA-PCR but
      negative throughout by both antigenemia and RT-PCR. These results suggest that
      the risk of CMV infection is low because the incidence of CMV activation in
      patients receiving PBSCT is low.

PMID- 9012932
TI  - Paranasal sinusitis following allogeneic bone marrow transplant.
AB  - In attempt to identify major clinical features of paranasal sinusitis following
      allogeneic BMT, we reviewed 44 consecutive cases diagnosed at the Hammersmith
      Hospital between August 1993 and December 1995. All patients had symptoms and
      signs characteristic of sinusitis. Plain radiographs and/or CT scans revealed
      fluid levels in 86.4% of patients, opacification in 9.1%, and marked mucosal
      thickening in 4.5%. Two-thirds of patients were diagnosed within 120 days of BMT.
      The WBC was less than 1 x 10(9)/1 in 16.3% of patients, the neutrophil count was
      less than 0.5 x 10(9)/1 in 18.6%, and serum immunoglobulins were depressed (< 6.7
      g/l) in 40.6%. Grade III-IV acute GVHD was present in 25.6% of patients and grade
      I-II in 66.7%; 68.6% developed chronic GVHD. There were 70.5% of patients
      receiving corticosteroids. Specific pathogens could not be identified in most
      cases. Pneumonia was present in 10 patients, seven of whom had Aspergillus
      species identified by bronchoalveolar lavage. Parainfluenza virus was isolated in
      three patients and Pseudomonas aeruginosa in two. Although all patients received
      antimicrobial therapy, 70.5% developed chronic sinusitis. Fatal complications did
      not occur. In 94 consecutive patients receiving allografts for CML during the
      period of study, WBC and neutrophil counts were lower 3 months post-BMT in
      patients who developed sinusitis (P < 0.02). Patients receiving higher doses of
      total body irradiation (13.2 and 14.4 Gy) had a greater probability of developing
      sinusitis (P = 0.023). Sinusitis occurred in only one of 37 patients receiving
      autologous transplants in the same period. Sinusitis is common following
      allogeneic BMT. Leukopenia is often present, but microbiological diagnosis is
      difficult, and progression to chronic sinusitis common.

PMID- 9012933
TI  - Cardiovascular function in children following bone marrow transplant: a cross
      sectional study.
AB  - Sixty-three patients who had undergone a BMT at age < or = 18 years were
      evaluated cross-sectionally to determine cardiac function as well as the long
      term prevalence, types, severity, and risk factors of cardiac abnormalities.
      Patients were > or = 1 year post-BMT and were evaluated by history, resting ECG,
      echocardiography (ECHO), exercise treadmill test, chest X-ray, pulmonary function
      tests and review of past cardiac studies. Patients were assigned a New York Heart
      Association (NYHA) class based on an activity and cardiac symptoms questionnaire.
      Pretransplant preparative regimens included high-dose cyclophosphamide (CY) and
      total body/lymphoid irradiation (n = 38), CY in combination with other
      chemotherapy (n = 22), and other drug combinations (n = 3). Forty patients
      (63.5%) had received prior anthracyclines (median 307 mg/m2). Patients' ages
      ranged from 1.9 to 32 years (median 10.9 years) with median follow-up of 3.3
      years (range 1-16.3 years). Twenty-six patients (41.3%) had a cardiac abnormality
      detected at follow-up. In 21 patients the abnormal finding had not been present
      at the pre-BMT evaluation. Ten patients (16.4%) had resting ECG abnormalities.
      Left ventricular ejection fraction (LVEF) by ECHO was mildly decreased to 50-54%
      in three patients and markedly decreased to 40% in one patient. Only one patient
      (1.7%) developed a mildly abnormal shortening fraction of 27%. All patients with
      ECHO abnormalities were asymptomatic. Twenty-three of 31 patients > or = 9 years
      of age (74%) who underwent a treadmill exercise test had a borderline or abnormal
      response to exercise. There was no correlation between demographic factors,
      previous therapy, preparative regimen or length of follow-up with the post-BMT
      ECG, ECHO and treadmill abnormalities. Overall, eight patients (12.7%) were
      symptomatic and NYHA class II or III, and all had abnormal exercise tests. The
      presence of symptoms and NYHA class were predictors for oxygen consumption during
      exercise (P = 0.03 and 0.02, respectively) and tended to predict overall
      treadmill results also. Late cardiac abnormalities do occur following BMT in
      childhood and thus, there is a clear need for continued, serial long-term cardiac
      evaluation in transplant survivors. Evaluations should include exercise stress
      testing to detect inadequate cardiac output as well as oxygen consumption during
      exercise.

PMID- 9012934
TI  - Registered bone marrow donors' views on bodily donations.
AB  - The attitudes of 463 potential bone marrow donors toward blood donation, kidney
      donation in life, organ donation after death, autopsy, and donation of the whole
      body for anatomic dissection were surveyed, using a questionnaire that had
      previously been employed for assessing the attitudes of the public. The response
      rate was 96%. Three quarters of the respondents were blood donors and recruited
      via the blood center. The proportion that accepted the procedures varied between
      24% for anatomic dissection and 97% for autopsy. Differences were small between
      individuals with positive attitudes and individuals who had also actively taken
      steps to activate these attitudes. Compared with the public, the bone marrow
      donors were more positive to all kinds of bodily donations. The conclusion is
      that if one is prepared to give from the body in life, one is also prepared to
      give after death. The results may indicate less death anxiety and fear of
      physical injury, and less fear of chaos either with or without altruism compared
      to the public.

PMID- 9012935
TI  - Disseminated superficial porokeratosis after autologous bone marrow
      transplantation.
AB  - A case of disseminated superficial porokeratosis (DSP) is reported in a black man
      5 years after autologous bone marrow transplantation (BMT) for acute
      promyelocytic leukemia. Porokeratosis is a rare hyperkeratotic disorder arising
      from clonal keratinocytes with a high potential to develop squamous cell
      carcinoma. Inherited forms are classical but recent observations of acquired
      porokeratosis have been reported in immunocompromized patients (AIDS, immune
      disorders, immune suppressive drugs or organ transplantation). Two cases of DSP
      have been reported after allogeneic BMT in patients treated for chronic GVHD. Our
      case is the first one after autologous BMT, in a black man, on no
      immunosuppressive drug at the time of diagnosis of DSP. Hematopoietic and immune
      reconstitution was apparently complete. The cancer-prone character of
      porokeratosis could be favored by total body irradiation used in conditioning
      regimen. Thus, porokeratosis has to be associated with other late effects after
      BMT such as HCV seropositivity, cataract and infertility that were observed in
      this patient.

PMID- 9012936
TI  - Clinical features and successful recovery from disseminated nocardiosis after
      BMT.
AB  - Nocardiosis has rarely been described after BMT. When the doses of
      immunosuppressive therapy were tapered, a 46-year-old BMT recipient developed
      chronic graft-versus-host disease (GVHD) and immunosuppresive drugs were
      increased. Sixteen days later the patient developed nocardiosis diagnosed by lung
      biopsy. Trimethoprim/sulfamethoxazole (TMP/SMZ) was initiated but the doses were
      reduced because of rising creatinine levels. Skin and cerebral dissemination of
      nocardiosis was observed and TMP/SMZ doses were increased. After 4 months, the
      brain lesion was unaltered despite resolution of pulmonary lesions. Clinical
      improvement was observed after drainage of the brain abscess.

PMID- 9012937
TI  - Successful hematopoietic reconstitution by transplantation of umbilical cord
      blood cells in a transfusion-dependent child with Diamond-Blackfan anemia.
AB  - A 4-year-old boy with Diamond-Blackfan anemia and a history of multiple
      transfusions underwent umbilical cord blood transplantation from his HLA
      identical female sibling born by vaginal delivery at 38 weeks. The patient was
      prepared with busulfan, cyclophosphamide and antilymphocyte globulin.
      Methotrexate and cyclosporin A were given for the prophylaxis of GVHD. Regimen
      related toxicity was not observed and successful engraftment occurred, including
      the erythroid series. No evidence of acute or chronic GVHD has been observed for
      14 months after transplantation. This is the first case of successful umbilical
      cord blood transplantation to a patient with Diamond-Blackfan anemia.

PMID- 9012938
TI  - Suicide and suicidal ideation after marrow transplantation.
AB  - Two cases of patients who attempted suicide following BMT and one case of a
      patient with suicidal ideation during his isolation period for BMT are reviewed.
      The factors which contributed to this situation are investigated. Finally, issues
      relating to psychological interventions are briefly discussed.

PMID- 9012939
TI  - Autologous bone marrow transplantation for primary nasal T/NK cell lymphoma.
AB  - Primary nasal T or NK cell lymphoma is rarely seen in the Western population but
      is more common in the Orientals. Although it often presents with localized
      disease, the prognosis is generally poor. Long-term remission is seen in only 50%
      of patients with stage I disease despite aggressive treatment with chemotherapy
      and radiotherapy, and is invariably fatal if disseminated. Conventional
      chemotherapy for relapsed disease is usually not successful. Since 1992, three
      patients with relapsed primary nasal T/NK cell lymphoma have received high-dose
      chemotherapy with autologous bone marrow rescue at Queen Mary Hospital, Hong
      Kong. High-dose cyclophosphamide, BCNU and etoposide were used for conditioning.
      Two of them had a favourable response and remained in complete remission at 12
      and 44 months post-transplant. The third patient unfortunately had a systemic
      relapse 6 months after the transplant. It appears from this experience that, like
      other aggressive non-Hodgkin's lymphomas, high-dose chemotherapy and autologous
      bone marrow rescue is an effective treatment for relapsed primary nasal lymphoma
      following failure of conventional chemotherapy and radiotherapy.

PMID- 9012940
TI  - Rhabdomyolysis associated with septicemia after autologous bone marrow
      transplantation.

PMID- 9012941
TI  - Thalidomide-responsive chronic pulmonary GVHD.

PMID- 9012942
TI  - The effectiveness of DRL in the management and treatment of severe behaviour
      disorders following brain injury.
AB  - Effective management of behaviour disorders following brain injury is essential
      if individuals are to achieve their rehabilitation potential. Best practice
      dictates that the intrusiveness of any operant approach used be minimal, remain
      in operation for the shortest time possible, and emphasize skill building.
      Ideally, treatment gains should maintain following its withdrawal. Reinforcement
      methods fulfil these criteria in that they are less intrusive, concerned with the
      establishment of pro-social behaviours, and encourage positive staff-patient
      interaction. While their efficacy has been well documented with other clinical
      populations, less is known regarding treatment of behaviour disorders in
      survivors of brain injury. Some existing studies are characterized by
      methodological weakness that limit understanding of any contribution made to
      observed improvement, and little is known regarding maintenance of treatment
      effects. In this paper the effectiveness of a variant of differential
      reinforcement, DRL, will be examined. Three cases will be presented which
      demonstrate increased behavioural control in response to the use of DRL. A
      strength of this paper is that the use of appropriate single-case design
      methodology, and follow-up data up to 18 months after treatment, permits more
      robust conclusions regarding the efficacy of DRL to be made. These are discussed,
      together with practical points regarding programme design.

PMID- 9012944
TI  - Tc-HMPAO SPECT in persistent post-concussion syndrome after mild head injury:
      comparison with MRI/CT.
AB  - The purposes of this study were: (1) to determine the prevalence of abnormal
      99mTc-HMPAO SPECT scans in patients suffering from persistent post-concussive
      syndrome (PPCS) after mild closed head injury (CHI); (2) to compare SPECT with
      structural neuroimaging (MRI and CT) in patients with mild CHI; and (3) to
      investigate correlations between SPECT and clinical data obtained from the
      patient sample (neuropsychological testing, demographics, psychiatric diagnoses).
      Forty-three patients were included. SPECT was read as abnormal in 53% of patients
      and showed a total of 37 lesions while MRI was read as abnormal in 9% and CT scan
      in only 4.6% of patients after mild CHI. SPECT appears to be more sensitive in
      detecting cerebral abnormalities after mild CHI, especially in patients with PPCS
      symptoms, than either CT or MRI. No statistically significant relationship was
      found between SPECT scan abnormalities and age, past psychiatric history, history
      of substance abuse, or history of multiple CHI. Education level did not differ
      between patients with normal and abnormal SPECT. Current neuropsychiatric
      symptoms did not seem to have any impact on the results of SPECT scan.

PMID- 9012943
TI  - Prevalence of speaking and hearing disabilities among adults with traumatic brain
      injury from a national household survey.
AB  - The purpose of this study is to provide prevalence estimates of the
      sociodemographic characteristics and extent of speaking and hearing disabilities
      among a community-based sample of adults (15 years and older) who have survived
      traumatic brain injury (TBI). This report is based on the Canadian Health and
      Activity Limitation Survey (1986-87), a national household survey of self
      reported disabilities. Results indicate that adults with TBI with speaking or
      hearing difficulties tend to be male, middle-aged and older, urban dwellers, of
      relatively low income levels who are limited at work. Over 75% of adults with
      speaking difficulties report difficulty being understood by people outside their
      immediate family context. Hearing difficulties rise dramatically from 75%
      occurring with one communication partner to over 96% occurring with three
      partners. The mean duration of disabilities is 12.7 years for speaking and 13.5
      years for hearing. More than 80% of adults with communicative difficulties have
      co-occurring disabilities of mobility and agility. Results have specific
      implications for functional assessment of adults with TBI and service delivery
      decision-making.

PMID- 9012945
TI  - Screening for visual-perceptual deficits following closed head injury: a short
      form of the Visual Form Discrimination Test.
AB  - The purpose of this study was to evaluate the concurrent validity and clinical
      utility of a short form of the Visual Form Discrimination Test in persons with
      closed head injuries (n = 62). Given the homogeneity of the items, and patients'
      apparent consistency in responding, we hypothesized that scores from an eight
      item short form would be highly similar to the scores from the full version of
      the test (i.e. 16 items). The mean difference between the short form and full
      version was less than one point, and the correlation between the two forms was
      0.86. Applying a clinical decision rule resulted in a 'normal/impaired' overall
      correct classification rate of 98.4%. The short form shows considerable promise
      as a brief test of visual discrimination in persons with closed head injuries.

PMID- 9012946
TI  - Anxiety and depression in elderly patients receiving treatment for cerebral
      tumours.
AB  - Little is known regarding affect and the quality of life of elderly persons with
      malignant brain tumours. More elderly patients are currently being diagnosed with
      primary malignant CNS tumours and current, aggressive treatment has extended
      median life expectancy. This case study indicated significant levels of clinical
      depression and anxiety may be experienced. Additionally, trait anxiety was found
      to increase with tumour progression. The patient's concern regarding loss of
      conjugal closeness and social inactivity was identified for the first time in
      persons with malignant brain tumours. Being progressively less active physically,
      and more isolated emotionally, this patient used her relatively good general
      intellectual abilities to worry about her situation. At the present time
      integration into the community and distress over her ability to be assertive
      decreased. Practical barriers to the delivery of psychological services were
      encountered and are likely to have been under appreciated.

PMID- 9012947
TI  - Eating in side-lying facilitates rehabilitation in neurogenic dysphagia.
AB  - A 26-year-old man who had sustained a traumatic head injury aspirated when fed in
      the upright position. By contrast, when fed in the side-lying position swallowing
      improved and there was no aspiration. Implications for management are discussed.

PMID- 9012948
TI  - Community-based rehabilitation of the person with a severe brain injury.
AB  - Community-based rehabilitation (CBR) recognizes that in the secure, loving
      environment of his/her own home, the person with a brain injury and the family,
      provided with support and guidance, can effectively augment or supersede hospital
      based rehabilitation. This paper will explore the methods used to establish a
      rehabilitation programme in the home, the initial moves, the family dynamics, the
      advantages, and some of the programmes required for the restoration of function
      of sensory, cognitive and motor abilities. The mobilization of the therapy
      workforce, including the use of extended family and trained volunteers from the
      community, is explained. The importance of volunteer meetings and the continuing
      education of the family and volunteers is emphasized. Respite care for the family
      and the aim of returning the family towards normality is considered. The enormous
      cost/benefit of the community-based rehabilitation is detailed, and comparative
      costs between this method and hospital-based rehabilitation are provided.

PMID- 9012949
TI  - Community based rehabilitation.

PMID- 9012992
TI  - The staging interval for bilateral carotid endarterectomies.

PMID- 9012993
TI  - 'Medical cost savings through stroke prevention from 100 consecutive new carotid
      duplex scans', by G.S. Lavenson and D. Sharma, Cardiovascular Surgery, 1996, 4:
      753-58.

PMID- 9012994
TI  - Matas Lecture. Heparin--controversies and misconceptions.
AB  - The previous dogmas regarding heparin therapy are currently being challenged. It
      is apparent that the experimental work on which guidelines for heparin therapy
      are based do not necessarily have any relevance clinically. Once clotting has
      been initiated, there are multiple factors that result in a relative refractory
      response to heparin anticoagulation. In addition, it is now apparent that
      heparin's effect cannot be accurately monitored with current tests of
      anticoagulation. Most importantly, the risk of bleeding does not correlate with
      heparin levels but with clinical risk factors and to the presence or absence of
      functioning platelets. For this reason, sufficient heparin should be given
      initially to ensure that clotting is under control. If this is not done, all of
      the risk of heparin anticoagulation is assumed with none of the benefit. Life
      threatening clotting conditions require high doses of heparin, equivalent to
      those required for cardiopulmonary bypass. Even though there is no good
      laboratory test available to ascertain the adequacy of anticoagulation,
      assessment of the clinical response is sufficient. When heparin levels are
      adequate, clinical improvement is evident as manifest by decreased pain and
      improvement in well-being, cardiac function, and/or collateral flow.

PMID- 9012995
TI  - Minimally invasive surgery for perforator vein incompetence.

PMID- 9012996
TI  - The Perth endoluminal bifurcated graft system--development and early experience.
AB  - The study aim was to develop a reliable endoluminal graft system that would
      enable the deployment of a bifurcated graft for infrarenal abdominal aortic
      aneurysms. A life-size plastic model was made of an abdominal aorta and iliac
      arteries, with a 50-mm infrarenal abdominal aortic aneurysm. This model was used
      to develop and test self-expanding graft systems, based on a barbed Gianturco
      stent and series of stainless-steel 'Z' stents within a woven Dacron graft. The
      bifurcated system developed involves a trouser graft with one long leg and one
      short. This graft-system is delivered through one femoral artery with deployment
      of the proximal aortic end infrarenally and the longer trouser leg within the
      ipsilateral common iliac artery. The short trouser leg is left hanging free
      within the distal end of the aneurysm cavity, just above the bifurcation. It is
      held open by a self-expanding stent and is cannulated from the contralateral
      femoral artery with a guide wire. A simple straight self-expanding stented graft
      is then deployed to extend this short trouser leg down into the common iliac
      artery, effectively creating an extension to the short leg. The graft system has
      been deployed in 21 patients with satisfactory exclusion of the aneurysm in 17
      (81%). There has been one mortality and no conversion to open repair. All 17
      aneurysms remain excluded at median follow-up of 30 (range 4-60) weeks. None of
      the four graft stents that leaked (two proximal and two distal) sealed
      spontaneously. Deployment of the uncovered Gianturco stent across the renal
      artery origins in 18 cases (85%) has not been associated with renal artery
      occlusion or deterioration in renal function at a median follow-up of 30 (range 4
      60) weeks. The ability to deploy a bifurcated system increases the potential for
      endoluminal treatment of abdominal aortic aneurysm.

PMID- 9012997
TI  - Survival and aortic events after graft replacement for thoracoabdominal aortic
      aneurysm.
AB  - Graft replacement remains the procedure of choice for patients with
      thoracoabdominal aortic aneurysm. Since there is little information regarding the
      long-term survival following these major vascular operations which may carry a
      risk of various late complications, a retrospective analysis of 10 years follow
      up was undertaken. The results of 172 consecutive operations for thoracoabdominal
      aortic aneurysm were analysed retrospectively. Hospital mortality rate was 10.5%.
      Temporary postoperative haemodialysis was necessary in 10.4% of cases and
      paraplegia occurred in 8.2%. The mean (s.e.) overall cumulative 2-, 5- and 10
      year observed survival rate was 76(3.4), 53(4.5) and 19(7)%, respectively while
      expected survival of a background population at 2, 5 and 10 years was 94%, 85%
      and 71%, respectively. Reoperation for an early (< 7 days) or late (> 7 days)
      aortic event was necessary in 31 patients. If performed electively, the hospital
      mortality rate for late aortic reoperation was only 7% but an emergency
      reoperation, hospital mortality rate was 100%.

PMID- 9012998
TI  - Advances in the surgical repair of ruptured abdominal aortic aneurysms.
AB  - Over the past two decades, the mortality rate for elective repair of infrarenal
      abdominal aortic aneurysms has improved to an acceptable level (< 5%). However,
      surgical results of ruptured abdominal aortic aneurysms have remained fairly
      constant with about 50% in hospital mortality rates. Growing experience with the
      use of the left retroperitoneal exposure for elective aortic surgery allowed the
      authors to extend the use of this technique to the repair of ruptured abdominal
      aortic aneurysm. The extended left retroperitoneal approach using a
      posterolateral exposure through the 10th intercostal space allowed the surgeon
      expeditiously and reliably to obtain supraceliac aortic control by dividing the
      left crus of the diaphragm in all patients. In total, 104 aortic replacements
      were performed for ruptured abdominal aortic aneurysm during the past 7 years. Of
      these patients, 87 were men and 17 women; mean(range) age was 72(52-95) years.
      Hemodynamic instability (as defined by a systolic blood pressure of < 90 mmHg)
      was present before surgery in 41% (43/104) of patients. The operative mortality
      rate was 27.9% (29/104). Preoperative hemodynamic instability, time of operative
      delay and aortic cross-clamp time did not correlate with operative mortality. The
      median duration of intensive care unit stay was 4 (range 1-60) days and hospital
      stay 11 (range 6-175) days. The results of this series identified that a change
      in the operative technique for the repair of ruptured abdominal aortic aneurysm
      beneficially affected patient survival. The authors suggest that expeditious
      supraceliac control without thoracotomy is an excellent alternative and offers an
      advantage in the surgical management of ruptured abdominal aortic aneurysm.

PMID- 9012999
TI  - Results of 1000 consecutive elective abdominal aortic aneurysm repairs.
AB  - In order to identify major risks for death and complications from elective repair
      of abdominal aortic aneurysm, the authors analyzed their experience with the last
      1000 such repairs over a 15-year period. Of the patients, 772 were men and 228
      were women; average age was 70 (range 37-92) years. Some 20% of the patients had
      severe chronic obstructive pulmonary disease and 33% had baseline creatinine
      level > 115 mumol/l. Fifteen patients were dialysis-dependent and 24% (242/1000)
      had significant cardiac disease. Operation used a retroperitoneal approach in 834
      patients and a transperitoneal approach in 166. The perioperative mortality rate
      was 2.4%, but this did not change either chronologically or with technique: some
      50% of the deaths were due to cardiac causes. Renal and pulmonary impairment did
      not affect mortality or complication; 64% of non-fatal complications were
      distributed in the renal (17%), pulmonary (19%) and cardiac groups (28%). The
      authors' experience showed that patients with cardiac disease remain at
      significant risk for post-abdominal aortic aneurysm repair complications in spite
      of selective preoperative cardiac evaluation. Renal and pulmonary risk factors
      did not cause additional mortality or morbidity. They suggest that elective
      abdominal aortic aneurysm repair can be performed with low mortality and
      morbidity, even in increasing numbers of high-risk patients.

PMID- 9013000
TI  - Surgical treatment of abdominal aortic aneurysms of octogenarians.
AB  - The purpose of this study was to determine whether elective abdominal aortic
      aneurysmectomy in octogenarians is justified or may even be advisable. Between
      January 1986 and August 1993, 30 octogenarians of mean age 83.1 (range 80-93)
      years underwent abdominal aortic aneurysmectomy. Patients were divided into two
      groups: group 1 (n = 9) underwent elective surgical repair; group 2 (n = 21)
      underwent emergency procedure. In 28 patients location of the abdominal aortic
      aneurysm was infrarenal; two patients presented with a juxtarenal aneurysm. The
      average aneurysm diameter was similar in both groups (group 1, 68.8 mm; group 2,
      83.5 mm, P = n.s.). In group 2, two patients had free peritoneal rupture, one
      presented with rupture into the duodenum and one with penetration into the vena
      cava. Rupture was confined to the retroperitoneum in another 15 patients. Two
      patients had an expanding aneurysm. Hospital mortality rate was zero in group 1
      and 42.8% in group 2 (P = 0.011). Most early deaths were related to cardiac
      disease. The overall complication rate was 22% in group 1 and 62% in group 2.
      Mean intensive care unit time was 1.8 (range 1-3) days in group 1 and 3.6 (range
      1-8) days in group 2 (P = 0.47). The 5-year survival rate was 67% in the
      electively managed group and 34% in the emergency group.

PMID- 9013001
TI  - Potential influence of intraluminal thrombus on abdominal aortic aneurysm as
      assessed by a new non-invasive method.
AB  - Intraluminal thrombus may play a role in abdominal aortic aneurysm pathogenesis
      and rupture. The purpose of this work was to demonstrate the feasibility of a new
      non-invasive method for the determination of the biomechanical features of the
      aortic wall and luminal boundary in abdominal aortic aneurysm containing
      intraluminal thrombus. Automated ultrasonographic measures of infrarenal aortic
      cross-sectional area (A) were obtained on-line along with non-invasive arterial
      pressure (p) from eight patients of mean (s.e.m.) age 74(3) years, with abdominal
      aortic aneurysm (mean dimensions 5.9(0.4) x 5.3(0.5) cm) containing intraluminal
      thrombus. Luminal boundary and abdominal aortic aneurysm wall were scanned
      separately. Compliance (C) was computed as C = (Amax - Amin)/[Amax(Pmax - Pmin)],
      where 'max and 'min' represent maximum and minimum values, respectively. Mean
      compliance was lower for the abdominal aortic aneurysm wall alone than for the
      luminal surface enclosed by intraluminal thrombus: 4.0(0.9) x 10(-4)/mmHg versus
      9.8(1.7) x 10(-4)/mmHg (P < 0.01). Intraluminal thrombus area was nearly constant
      over the cardiac cycle, indicating that the thrombus is virtually incompressible.
      This noninvasive method to assess biomechanical features of abdominal aortic
      aneurysm has potential to further the understanding of the influences of
      intraluminal thrombus on aneurysm disease.

PMID- 9013002
TI  - Polytetrafluoroethylene grafts for carotid repair.
AB  - Polytetrafluoroethylene grafts are well established for bypassing occlusive
      disease in the lower limb but there are few reports which deal with the long-term
      results of such grafts in the neck. The present study was undertaken to evaluate
      the immediate and long-term results of polytetrafluoroethylene grafts for carotid
      repair. Between 1982 and 1991, 591 carotid operations (mostly endarterectomies)
      were performed by the authors. In 32 cases a polytetrafluoroethylene graft was
      used to replace (n = 12) or to bypass (n = 20) a stenotic lesion of the internal
      carotid artery. Postoperative angiography was obtained in all patients and the
      follow-up extended from 1 month to 9 years (mean 30 months) with clinical and
      duplex scan surveillance. There were no deaths within the first postoperative
      month. There was one acute postoperative stroke (3%) caused by plaque
      dislodgement and one symptomless occlusion demonstrated by routine angiography.
      During follow-up, seven patients died from other causes. No patient developed new
      neurological symptoms but routine duplex assessment showed one symptomless graft
      occlusion. The cumulative survival rate was 96% at 1 year and 91% at 4 years. The
      cumulative primary patency rate was 93% at 1 month, 89% at 1 year and 89% at 4
      years. In specific situations polytetrafluoroethylene grafting is an adequate
      alternative to carotid endarterectomy but is not recommended by the authors as a
      routine procedure because of its occlusion rate (> 6.2%).

PMID- 9013003
TI  - Experimental evaluation of bleeding complications, thrombogenicity and neointimal
      characteristics of prosthetic patch materials used for carotid angioplasty.
AB  - Experiments were designed to compare perioperative blood loss, early
      thrombogenicity and morphologic and functional characteristics of the neointima
      of three types of prosthetic materials used for carotid artery patch angioplasty.
      Bilateral carotid patch angioplasties were performed in 20 dogs, using 20 gelatin
      impregnated fluoropassivated Dacron (GIF), 10 untreated knitted Dacron and 10
      expanded polytetrafluoroethylene (PTFE) patches (5 cm2). Intraoperative blood
      loss, platelet deposition at 24 h and neointimal morphology at 6 weeks after the
      operation were assessed. Bioassay of the neointima was performed at 6 weeks in 16
      patches. Mean (s.e.m.) blood loss was significantly less in GIF patches (14.7
      (2.7) ml) compared with either PTFE (75.6 (24) ml) or untreated Dacron (64.3
      (9.5)) (P < 0.005). Mean (s.e.m.) platelet deposition in GIF patches (1380 (328)
      platelets/cm2) was approximately 50% less at 24 h than in untreated Dacron (2562
      (1035) platelets/cm2) or PTFE (2140 (998( platelets/cm2) patches (P < 0.05).
      Neointimal coverage was greater in PTFE (94 (1.3%)) compared with GIF (79 (2.7%))
      or untreated Dacron (86 (2.4%)) patches (P < 0.05). The thickness of the
      neointimal layer of PTFE (0.5 (0.01) mm) patches was greater than other patch
      types; GIF (0.2 (0.01) mm) or untreated Dacron (0.3 (0.01) mm) (P < 0.50). Under
      bioassay conditions, acetylcholine caused release of vasoactive relaxing
      factor(s) from all patches. However, relaxations from baseline were less with GIF
      patches (-37.9 (11.7)% versus -54.5(9.6( for untreated Dacron; -50.2 (15.2)% for
      PTFE) (P = n.s.). Endothelin-1 release occurred from all patches and was
      increased with the extent of neointimal coverage. These data demonstrate that GIF
      patches caused the least perioperative bleeding, were the least thrombogenic at
      24 h and developed the thinnest neointima at 6 weeks. All patch materials
      developed a functioning neointima.

PMID- 9013004
TI  - Medical cost savings through stroke prevention from 100 consecutive new carotid
      duplex scans.
AB  - Recent studies have shown that carotid endarterectomy for significant lesions
      lowers the risk of stroke and also reduces medical costs by averting the high
      costs of strokes. However, there has been no information on the cost effect of
      duplex ultrasound examination which has evolved as the prime means of discovering
      these carotid lesions. This study reviewed the findings and management of 100
      consecutive new patients referred for duplex ultrasound management of the carotid
      arteries and the cost effects resulting. Seventy-three patients with < 70%
      stenosis were managed non-operatively; the remaining 27 with 33 lesions producing
      > 70% stenosis were treated by carotid endarterectomy. It was estimated that 6.5
      patients would have had a stroke within 18 months if not operated on. While the
      medical costs of these strokes would have been $958,838, the cost of avoiding
      them was $300,494; the result was a significant medical costs saving of $658,344.

PMID- 9013005
TI  - Bilateral carotid endarterectomy during the same hospital admission.
AB  - The efficacy of carotid endarterectomy for the prevention of strokes has been
      well demonstrated in recent multicenter randomized trials. However, patients
      presenting with bilateral significant disease pose a difficult problem to the
      vascular surgeon. Currently, bilateral carotid endarterectomies are staged at
      varying intervals between operations, with surgeon and patient weighing the risks
      of waiting for surgery versus the risks of having both procedures done within a
      shortened interval. There are few data and no consensus on the optimal time
      interval between these operations. In order to evaluate the timing of carotid
      endarterectomies in patients with severe bilateral disease, the authors reviewed
      their experience with patients who had bilateral procedures performed during one
      hospitalization. Over the past 5 years, they have performed 204 such carotid
      endarterectomies in 102 patients. Cervical block anesthesia was used in 99%
      (201/204) of these procedures. All patients either had symptomatic disease, > 60%
      stenosis or severe ulcerative plaque as defined by duplex scan and/or
      preoperative angiography. Symptomatic stenoses were the operative indications in
      39% (80/204) of the patients; the remaining 61% (124/204) were symptom-free. The
      majority of patients (80%; 164/204) had their second procedure performed within 2
      days of their first operation. There was no operative mortality and only one
      permanent neurologic defect in this group for a combined stroke mortality rate of
      1%. Three patients (1.5%) had transient neurologic deficits postoperatively which
      completely resolved by discharge. These data show that bilateral carotid
      endarterectomies can be performed safely and effectively during one hospital
      admission with a short interprocedural interval and without an increase in
      mortality or morbidity.

PMID- 9013006
TI  - Access to the right renal artery from the left retroperitoneal approach.
AB  - One of the perceived limitations of the left retroperitoneal approach to the
      aorta is inadequate access to the right renal artery. Many consider the need for
      a concomitant right renal artery revascularization a contraindication to
      performing an aortic reconstruction through the left retroperitoneum. Exposure of
      the right renal artery can be difficult due to the posterior course of the artery
      behind the vena cava. However, when the aorta is transected, the right renal
      artery can be easily approached with anterior and cephalad displacement of the
      aortic root. Over the past 3 years, 52 patients have had right or bilateral renal
      artery revascularization via the left retroperitoneal approach; of these
      procedures, 37 were performed with concomitant aortic procedures. In total, 34
      patients had bilateral and 18 had unilateral revascularizations. Five patients
      had a transaortic endarterectomy performed, and 36 were bypassed with 6-mm
      expanded polytetrafluoroethylene side limbs from the aortic graft. Indications
      for revascularization were: 39 for suprarenal aortic bypass, seven for renal
      salvage and six for primary renovascular hypertension. All reconstructions have
      remained patent and all have been followed by serial duplex and renal flow scans
      (follow-up for 1-42 months). The operative mortality rate was 5.8% (3/52). There
      were no major cardiorespiratory complications in this group. Adequate exposure to
      the proximal right renal artery can be obtained through the left retroperitoneal
      approach to the aorta, and successful revascularization of one of both renal
      arteries can be technically performed with acceptable mortality and morbidity.

PMID- 9013007
TI  - Comparison of clinical follow-up and duplex surveillance of infrainguinal vein
      bypasses.
AB  - The evidence in support of surveillance has been principally based on the
      favourable primary-assisted patency of stenosed grafts following revision (60-80%
      at 5 years) compared with the poor secondary patency of revised occluded grafts
      (20-40% at 5 years). Both the capital cost and workload generated by surveillance
      are considerable. More information is needed on the benefits of surveillance
      compared with clinical follow-up. A retrospective comparison of 50 vein grafts
      (44 reversed, six in situ) undergoing colour-coded duplex surveillance and 50
      vein grafts (46 reversed, four in situ) under clinical follow-up, with duplex
      scans obtained only when clinically indicated, has been performed. Four (8%)
      stenoses of > or = 50% were identified in the surveillance group. One 50%
      proximal anastomotic stenosis failed to progress on sequential scans. Three
      stenoses were treated (one mid graft, two popliteal) by vein patch angioplasty
      (two cases) and transluminal angioplasty (one case). Both groups were followed-up
      for 12 months. Secondary patency at 12 months (88% surveillance; 80% clinical
      follow-up) was not significantly different (P = 0.3). Similarly, limb salvage at
      12 months (94% surveillance; 88% controls) was not significantly different (P =
      0.4). A large randomized prospective study comparing duplex surveillance and
      clinical follow-up is warranted.

PMID- 9013008
TI  - Subcutaneous, video-assisted saphenous vein harvest: report of the first 30
      cases.
AB  - Harvest of the saphenous vein is a commonly performed procedure in cardiovascular
      surgery. The incision required for its removal is the longest used anywhere. In
      this report, the authors describe a minimally invasive technique for removal of
      the vein. This has been used in 30 patients undergoing peripheral arterial bypass
      (n = 27), venovenous bypass (n = 2), and a saphenopopliteal fistula (n = 1).
      There were three perioperative complications: skin necrosis over tunnel (one),
      bulla (one), and saphenous vein injury (one). Harvest time averaged 1.25 h. There
      was minimal postoperative discomfort in the harvest site and minimal scarring.
      Endoscopic harvest of the saphenous vein differs from most laparoscopic
      procedures because of its linear course. Consequently, visualization and
      dissection is coaxial rather than triangulation. This study demonstrates the
      technical feasibility of vein harvest. Development of appropriate instrumentation
      for opening the optical cavity and vein manipulation will reduce operative times.

PMID- 9013009
TI  - Venous thrombotic complications of pregnancy.
AB  - A total 30,040 pregnancies were reviewed at one institution over 5 years to
      determine the incidence of venous thrombotic complications. Thirty-one patients
      experienced such complications related to pregnancy (incidence 0.1%); 13 had deep
      venous thrombosis and 14 had superficial venous thrombophlebitis diagnosed by
      duplex ultrasound. Four had pelvic vein thrombophlebitis diagnosed by computed
      tomography scan; three patients (one from each group) sustained a non-fatal
      pulmonary embolus. Of those with deep venous thrombosis, 10 (77%) were left
      sided, and three (23%) were right-sided. Three had a prior history of deep venous
      thrombosis and one of pulmonary embolism. Of those with superficial venous
      thrombophlebitis, seven (50%) were left-sided, six (43%) were right-sided, and
      one (7%) was bilateral. Most with deep venous thrombosis presented later in
      pregnancy; three in the first trimester, two in the second, three in the third,
      and five early postpartum. Most (10/14) with superficial venous thrombophlebitis
      presented within 48 hours of delivery. Distribution of thrombi in those with deep
      venous thrombosis was compared with 643 non-pregnant women with a similar
      condition. A pattern of proximal involvement on the left was found, with left
      common femoral vein (54% versus 28%, P = 0.03) and superficial femoral vein (62%
      versus 26%, P = 0.006) more often involved in pregnant patients. The average
      number of vein segments involved was greater on the left than the right (5.3
      versus 3.7). Symptoms of chronic venous insufficiency developed in three with
      deep venous thrombosis (25%) and in three with superficial venous
      thrombophlebitis (27%). None had recurrence of deep venous thrombosis. It is
      concluded that venous thrombotic complications associated with pregnancy are not
      necessarily benign, with the risk of pulmonary embolism and chronic venous
      insufficiency not limited to patients with deep venous thrombosis only.

PMID- 9013010
TI  - Treatment alternatives for axillary-subclavian vein thrombosis: long-term follow
      up.
AB  - Spontaneous axillary-subclavian vein thrombosis in young patients produces long
      term disability. Patients with secondary axillary-subclavian vein thrombosis
      usually require prolonged venous catheterization for chemotherapy or pacemaking.
      This study aimed to compare the early and late results of lytic versus
      anticoagulant therapy in the treatment of axillary-subclavian vein thrombosis,
      both spontaneous and secondary to central venous cannulation. Nine patients
      underwent conventional treatment (heparin and warfarin) (group 1), and 10 had
      initial lytic therapy followed by heparin and warfarin (group 2). Three patients
      had cervical or first rib resection. Thirteen patients had spontaneous thrombosis
      and six were secondary to central venous catheterization. The mean follow-up was
      36 months. Two of nine patients (22%) in group 1 and eight of 10 patients (80%)
      in group 2 had total venous recanalization and symptom resolution (P = 0.018). In
      the spontaneous axillary-subclavian vein thrombosis subset, one of six patients
      (17%) in group 1 and five of seven patients (71%) in group 2 had total venous
      recanalization and symptom resolution (P = 0.078). The average difference in cost
      per patient between groups 1 and 2 was $19,039. In conclusion, lytic therapy
      appears superior to anticoagulation in the treatment of axillary-subclavian vein
      thrombosis. However, such treatment is more expensive and its benefits should be
      carefully weighed against the cost in each case.

PMID- 9013011
TI  - Hyperhidrosis treated by thoracoscopic sympathicotomy.
AB  - Hyperhidrosis of the palms, axillae and face has a strong negative impact on
      social and professional life. The existing non-operative therapeutic options
      seldom give sufficient relief and have a transient effect. A definitive cure can
      be obtained by upper thoracic sympathectomy. The traditional open surgical
      techniques are major procedures and few patients and surgeons have found that the
      risk--benefit consideration favoured surgery. Since 1987, the authors have
      divided the upper thoracic sympathetic chain on 1163 patients with a simple
      endoscopic technique by using standard urological equipment. A bilateral
      procedure takes less than 20 min and requires just one night in hospital. There
      have been no mortality or life-threatening complications. Ten patients (< 1%)
      required intercostal drainage because of haemo- or pneumothorax. Horner's
      syndrome occurred in four cases. Primary failure occurred in 23 cases (< 2%) and
      24 (< 2%) developed recurrent symptoms. The patients with failure and recurrence
      were successfully reoperated on and only three have required a third operation.
      At the end of postoperative follow-up (median 31 months) 98% of the patients were
      satisfied. Endoscopic transthoracic sympathicotomy is an efficient, safe and
      minimally invasive surgical method for the treatment of palmar, axillary and
      facial hyperhidrosis.

PMID- 9013012
TI  - Expeditious management of ischemic invasive foot infections.
AB  - Management of infected ischemic diabetic limbs requires antibiotic therapy,
      abscess drainage, and revascularization. However, revascularization is often
      delayed for several days or weeks as the infection is controlled. In an effort to
      decrease hospital stay and costs and to increase limb salvage, a series of 974
      extremities with distal occlusive disease were managed with autogenous distal
      bypass. Some 136 of these limbs (125 diabetic) had severe invasive infections.
      These patients received intravenous antibiotics in all cases and abscess drainage
      if necessary. Vascular reconstruction was carried out as soon as possible, within
      48 h of admission. An in situ bypass was used preferentially (107 cases).
      Patients were maintained on intravenous antibiotics in the perioperative period.
      Partial foot amputations, when necessary, were performed in 111 cases, usually 3
      5 days after vascular reconstruction. There were no graft infections or major
      wound infections. There were two cases of skin edge necrosis requiring
      reoperation due to flap mobilization and consequent ischemia. Urgent
      revascularization with an autogenous conduit may be carried out in patients with
      invasive foot infections expeditiously, with high rates of limb salvage. Graft
      and wound infections are not common in this setting. Costly prolonged pre-bypass
      hospitalization in these cases is unnecessary.

PMID- 9013013
TI  - Arterial homografts--a possible solution to an infective dilemma.
AB  - Seven patients with infected arterial conduits (six with prosthetic bypass grafts
      and one autogenous vein anastomosis) with ten limbs at risk (three patients with
      bilateral groin infection) are reported. The most common site for infection was
      the groin and the most frequent organism cultured was Staphylococcus aureus.
      These patients were selected for arterial homograft implantation through infected
      fields as they were unsuitable for extra-anatomical prosthetic bypass or had
      inadequate autogenous tissue available for use as a bypass conduit, i.e. the
      alternative to homograft insertion was arterial ligation and potential limb
      sacrifice. The arterial homografts were obtained form brain-dead organ donors
      (human immunodeficiency virus, hepatitis B- and hepatitis C-negative) and stored
      at -80 degrees C until ready for use. All seven patients had initial success with
      their homograft procedures in terms of graft patency, limb salvage and control of
      infection, although two required early reoperation for haemorrhage. During the
      follow-up period (mean 24.5, range 6-52 months) three homografts have occluded at
      6, 13 and 29 months resulting in limb loss. Two patients have died at 48 and 52
      months from causes unrelated to their homograft procedures with functioning
      homografts and limb salvage. Two further patients remain alive with patent
      homografts at 7 and 20 months. The authors' experience suggests that arterial
      homografts have a role in overcoming arterial bypass infection, achieving wound
      healing and maintaining limb viability rather than resorting to arterial ligation
      and accepting major limb amputation.

PMID- 9013014
TI  - The impact of a short interval ( < or = 1 year) between primary and reoperative
      coronary artery bypass grafting procedures.
AB  - Reoperative (redo) coronary artery bypass grafting is an efficient treatment for
      patients with progressive coronary artery disease and those with conduit failure.
      Previous studies have demonstrated that a short time interval between primary and
      redo coronary artery bypass grafting is associated with a significantly higher
      mortality rate. In the present report this particular group have been
      specifically evaluated. Between 1 January 1990 and 1 October 1994, 383
      consecutive patients underwent redo coronary artery bypass grafting. Thirty-three
      patients (8.6%) were operated on at < or = 1 year (group 1) and 350 patients at >
      1 year after the primary bypass (group II). The main indications for redo in
      group I were graft failure (58%), incomplete revascularization (39%) and progress
      of disease (3%); respective values in group II were 26% 15%, and 23%. In
      addition, 36% of patients in group II had combinations of complications. Patient
      characteristics did not differ between groups, except a higher incidence of
      insulin-dependent diabetes in group I (P < 0.05). There was a higher incidence of
      left main stem stenosis of > 70% in group I (P < 0.05). Group I patients had a
      longer aortic cross-clamping time and needed thromboendarterectomy and patching
      of coronary vessels more often than did those in group II (P < 0.05). The
      internal mammary artery had been more frequently used at the primary coronary
      artery bypass grafting in group I (P < 0.01). The overall mortality rate was
      8.9%; that in group I was 18% and in group II, 8% (P < 0.05). There was a higher
      incidence of non-fatal myocardial infarction and a need for prolonged ventilatory
      support (> 24 h) in group I. Other postoperative complications did not differ.
      Significant risk factors for mortality in group I were preoperative Canadian
      Cardiovascular Society class > or = 3, unstable angina, need for urgent operation
      and left ventricular ejection fraction < 40%, and > or = 70% left main stem
      stenosis. In group II, the risk factors were: unstable angina, urgent operation,
      left ventricular ejection fraction < 40%, internal mammary artery not used at
      primary coronary artery bypass grafting and the need for coronary
      thromboendarterectomy. The 3-year survival and cardiac event-free survival did
      not differ between the groups. This study has confirmed that early redo coronary
      artery bypass grafting (< or = 1 year from primary bypass) is associated with an
      increased operative risk.

PMID- 9013015
TI  - Plasma endothelin-1 levels in adult patients undergoing coronary
      revascularization.
AB  - Cardiopulmonary bypass is thought to injure all endothelial cells, mainly by cell
      to-cell interaction with activated granulocytes which, augmented by endothelin-1
      (ET-1), enhance the generation of superoxide radicals. These radicals on the
      other hand, may sustain and prolong endothelial injury. In the present study, by
      means of a magnetic separation radioimmunoassay procedure, ET-1 levels were
      measured in 10 adult patients undergoing coronary artery bypass surgery, in 10
      perioperative phases, in order to reconfirm and further elucidate the effect of
      cardiopulmonary bypass on endothelial secretion of ET-1. ET-1 levels before
      cardiopulmonary bypass showed a definite rising trend, especially after median
      sternotomy. After induction of cardiopulmonary bypass, ET-1 levels increased
      significantly compared with preoperative values (P < 0.01). ET-1 levels in stable
      angina patients during and after aortic cross-clamping were strongly and
      positively correlated with preoperative mean pulmonary artery pressure (r = 0.79,
      n = 7, P < 0.05 and r = 0.92, n = 7, P = 0.05) respectively. After the first hour
      in the intensive care unit, ET-1 levels in three patients with unstable angina
      were considerably higher than in those with stable angina, a fact that deserves
      further consideration and study.

PMID- 9013016
TI  - Mitral valve reconstruction: long-term results of 120 cases.
AB  - Between January 1977 and December 1992, 120 patients underwent mitral valve
      reconstruction for pure mitral valve regurgitation (n = 88), or associated with
      mitral stenosis (n = 32). The mean age was 57.6 years. Some 89 patients were in
      New York Heart Association (NYHA) class III and IV; 61% were in atrial
      fibrillation. Four mechanisms of mitral regurgitation were assessed: dilatation
      of the annulus (group I: n = 10); increased amplitude of valve motion (group II:
      n = 62); restriction of valve motion (group III: n = 23), and mixed lesions
      (group IV: n = 25). Mitral valve repair was carried out using techniques
      described by Carpentier. Ring annuloplasty was performed in all patients. There
      were two operative deaths, and six late deaths. Mean patient follow-up was 41
      (range 2-142) months. The actuarial survival rate, excluding hospital deaths, was
      91.7% at 5 years and 89.1% at 8 years. Actuarial freedom from reoperation at 8
      years was 95(2)%. Freedom from all thromboembolic complications was 89.1% at 8
      years. Most survivors had improved to NYHA class I or II and postoperative
      Doppler echocardiography revealed satisfactory mitral valve competence in 83
      patients. Mitral valve reconstruction for mitral regurgitation using Carpentier
      techniques provides excellent long-term functional results and should be
      considered as the procedure of choice in patients referred for mitral
      regurgitation.

PMID- 9013017
TI  - Rhythm disturbances after mitral valve surgery: comparison between left atrial
      and extended trans-septal approach.
AB  - This study was undertaken to determine the incidence of postoperative arrhythmias
      in mitral valve surgery through the left atrium as compared with the extended
      trans-septal approach. All patients undergoing mitral valve surgery for acquired
      valve disease between 1 January 1991 and 31 December 1993 were reviewed. Only
      patients with preoperative normal sinus rhythm were included in this study. End
      points for analysis were: 'any supraventricular arrhythmia'; 'atrial fibrillation
      of flutter'; and 'ectopic atrial or junctional rhythm'. All predictive factors
      with a P-value < 0.10 in univariate analysis were entered into the multivariate
      proportional hazard model of Cox. Some 72 patients were included for analysis. No
      variables were independently predictive of 'any supraventricular arrhythmia'. Age
      is an independent predictor of 'atrial fibrillation or flutter' and surgical
      approach of 'ectopic atrial or junctional rhythm'.

PMID- 9013018
TI  - Total arterial myocardial revascularization without cardiopulmonary bypass.
AB  - The risks associated with cardiopulmonary bypass have led to an interest in
      coronary surgery without the use of such a bypass. Six patients of mean(s.d.) age
      62.0(8.0) (range 52-71) years were selected for elective coronary surgery without
      cardiopulmonary bypass. In five cases a midline sternotomy and in one case a
      small anterolateral thoracotomy were performed; in the latter case the harvesting
      of the proximal end of the left internal mammary artery was video-assisted by
      thoracoscopy. The left internal mammary artery was used in all cases; the right
      internal mammary artery was used in one case, the radial artery in four, the
      inferior epigastric artery in two and the right gastroepiploic artery inn one. No
      patient died or had a stroke. There were no postoperative episodes of low cardiac
      output syndrome or perioperative myocardial infarction. All patients were
      extubated within a few hours after surgery. The mean(s.d.) intensive care unit
      and hospital stays were 1.3(0.5) and 5.0(0.9) days, respectively. Total arterial
      myocardial revascularization without cardiopulmonary bypass using composite
      grafts, is a new and promising technique that is feasible with low risks and good
      early results in selected cases.

PMID- 9013019
TI  - Angina pectoris treated by thoracoscopic sympathecotomy.
AB  - Open surgical sympathectomy has previously been shown effective in relieving
      severe angina pectoris. The method was hampered by high morbidity and mortality.
      The authors have developed a minimally invasive technique of dividing only the
      sympathetic chain endoscopically and obtained good results with no serious
      complications in patients operated on for severe palmar hyperhidrosis. This
      method was used in 43 patients with severe angina pectoris who were not eligible
      for coronary artery bypass grafting or percutaneous transluminal coronary
      angioplasty. There was no mortality or any severe complications. Some 19 patients
      became symptom-free while 22 were improved and two unchanged after surgery. The
      frequency of anginal attacks was significantly reduced, as was the consumption of
      nitroglycerine tablets. The maximum exercise capacity was significantly increased
      and ST-segment depression reduced.

PMID- 9013020
TI  - Pathogenesis and prognostic significance of conduction abnormalities after
      coronary bypass surgery.
AB  - Of 200 men who underwent isolated coronary bypass graft surgery, 40 (20%)
      developed new postoperative, persistent conduction abnormalities. The
      pathogenesis of conduction abnormalities was examined by relating their presence
      to that of significant proximal left coronary disease before surgery, and to
      various intraoperative factors that included indices of myocardial preservation
      and revascularization. Proximal left coronary disease was observed in 92 (46%) of
      200 patients, of whom 27 (29%) developed conduction abnormalities. In contrast,
      of the 108 patients without proximal left coronary disease, only 13 (12%)
      developed persistent conduction abnormalities (P < 0.01). Intraoperative factors
      appeared to have little or no role in the development of such abnormalities. It
      is concluded that the development of persistent postoperative conduction
      abnormalities is related more to proximal left coronary disease than to
      intraoperative factors and that such abnormalities do not progress during long
      term follow-up (average 53 months).

PMID- 9013021
TI  - Complex venous reconstruction for chronic iliofemoral vein obstruction.
AB  - A 35-year-old patient, physically very active, developed symptoms and signs of
      postphlebitic venous obstruction in the right lower extremity that was
      complicated by deep venous thrombosis, while recovering from a motorcycle
      accident. Duplex and venography demonstrated occlusion of the right superficial
      femoral vein and right external iliac vein. Strain-gauge plethysmography and
      measurements of venous pressures demonstrated functional obstruction. The patient
      underwent saphenous cross-femoral vein bypass, right saphenous-popliteal
      anastomosis accompanied with distal posterior tibial to saphenous vein
      arteriovenous fistula. Ten days following surgery, the arteriovenous fistula and
      the distal great saphenous vein closed spontaneously. The rest of the
      reconstruction remained patent as documented by duplex up to 24 months following
      the surgery. Clinically, the patient is doing well, tolerating heavy physical
      exertion as before his accident. The importance of selection of patients for
      venous bypass surgery is stressed. Only patients with co-existing anatomical and
      functional obstruction are good candidates for these procedures.

PMID- 9013022
TI  - False aneurysm of the inferior gluteal artery following penetrating buttock
      trauma: case report and review of the literature.
AB  - The case of a 28-year-old man who presented with a false aneurysm of the inferior
      gluteal artery 3 months after a penetrating wound to the buttock is reported.
      Percutaneous transcatheter embolization was unsuccessful. At operation, abdominal
      access was used for control, with a gluteal approach to provide exposure of the
      aneurysm. The presentation and management of patients with this pattern of injury
      are discussed, and the relevant literature reviewed.

PMID- 9013023
TI  - Duodenal obstruction following elective abdominal aortic aneurysm repair.
AB  - A case where duodenal obstruction complicated elective repair of abdominal aortic
      aneurysm is reported. A review of the literature shows that the incidence of this
      rare complication has probably been underestimated. Patients should be treated
      expectantly, regardless of the pathogenesis of the obstruction.

PMID- 9013024
TI  - Surgical removal from the descending aorta of a floating thrombus caused by blunt
      chest trauma.
AB  - A 44-year-old woman presented with a recurrent peripheral embolism. Her past
      history was remarkable for blunt chest trauma 7 years before presentation.
      Transoesophageal echocardiography showed a floating mass in the descending aorta.
      Operative and pathological findings revealed an aged thrombus. Reliable
      diagnostic methods and appropriate treatment can prevent further embolic events.

PMID- 9013026
TI  - Pharmacological model of catecholamine depletion in the hypothalamus of fetal and
      neonatal rats and its application.
AB  - 1. The present study aimed to develop a pharmacological model of catecholamine
      (CA) depletion in the hypothalamus during the period of its morphofunctional
      development, i.e. in fetal and neonatal rats of both sexes. 2. In the first
      series of experiments, pregnant females and, hence, fetuses were systemically
      treated daily from the embryonic day (E) 13 to E20 with the inhibitor of the CA
      synthesis alpha-methyl-m-tyrosine. The CA concentrations were subsequently
      measured in the fetal hypothalamus at E21 by high performance liquid
      chromatography with electrochemical detection (HPLC-ED). In the second series of
      experiments, neonatal rats were injected with neurotoxin, 6-hydroxydopamine
      and/or alpha-methyl-m-tyrosine daily from the 2nd postnatal day (P2) to P10. 3.
      The HPLC-ED assay of hypothalamic catecholamines (CA's) at E21 and P11 showed
      that both in fetuses and neonates, alpha-methyl-m-tyrosine caused more than 50%
      depletion of hypothalamic noradrenaline and adrenaline, while the dopamine (DA)
      level remained unchanged. The combined treatment of neonatal rats with alpha
      methyl-m-tyrosine and 6-hydroxydopamine resulted additionally in a 25% decreased
      level of DA. 4. The influence of CA deficiency on the developing hypothalamic CA
      system was further evaluated by measuring [3H]DA uptake by nervous tissue in
      vitro. 5. The CA deficiency caused a 50% drop of [3H]DA uptake by the
      hypothalamic tissue in treated fetuses suggesting a stimulating effect of CA's on
      the early development of the CA system. In pharmacologically treated neonatal
      rats [3H]DA uptake remained at the control level showing no influence of the CA
      deficiency on the developing CA system after birth. 6. The usefulness of the
      proposed pharmacological model for studying of CA influence on differentiating
      hypothalamic target neurons is discussed.

PMID- 9013028
TI  - Transient expression of neuropeptide Y (NPY) immunoreactivity in the developing
      hamster paraventricular thalamic area is due to apoptosis.
AB  - 1. A new population of neurons with transient expression of NPY immunoreactivity
      was described in the developing hamster paraventricular thalamic area. The
      present study was performed to discover whether this phenomenon is due to
      programmed cell death or apoptosis. 2. Toward this aim, immunocytochemical and
      electron microscopic examination of the paraventricular thalamic region, as well
      as DNA electrophoresis of tissue extracted from the described area, was performed
      on different stages of embryonic and postnatal development. 3. A sudden increase
      in neuropeptide Y immunoreactivity (NPY-IR) in the paraventricular thalamic area
      at embryonic day 14 (E14) was the first symptom of neuronal degeneration. 4.
      Electron microscopy revealed many neurons with large masses of condensed
      chromatin within nuclei and extracellular bodies. The affected cells had a
      convoluted shape and condensed cytoplasm. 5. DNA electrophoresis revealed a
      ladder of bands between 150 and 1000 bp that is specific for internucleosomal DNA
      fragmentation. 6. The data strongly suggest that developmental disappearance of
      NPY-IR neurons within the hamster dorsal thalamic area is due to apoptosis.

PMID- 9013029
TI  - Transient and sustained expression of FMRFamide-like immunoreactivity in the
      developing nervous system of Lymnaea stagnalis (Mollusca, Pulmonata).
AB  - 1. In the present study we have investigated the ontogeny of FMRFamide expression
      in the snail, Lymnaea stagnalis, from its first appearance to its distribution in
      young adults. 2. The first FMRFamide-like immunoreactive (FaLI) cells within CNS
      appear by E45 embryonic stage (premetamorphic veliger). The number of FaLI
      neurons increases throughout both pre- and post-hatching development. 3. Both
      transient and sustained expression of FMRFamide-like immunoreactivity by specific
      sets of neurons occurs. Two cells which transiently express immunoreactivity
      appear outside the future CNS by the stage E45. Other population of transient
      FaLI neurons includes bilaterally symmetric groups of cells in the cerebral and
      pedal ganglia during posthatching stages P1 (hatchlings) to P5 (juveniles). All
      other immunostained cells which appear during development maintain their
      transmitter phenotype into adulthood. 4. The possible role of FMRFamide-related
      peptides in the processes of morpho- and neurogenesis is discussed.

PMID- 9013027
TI  - Tyrosine hydroxylase-containing neurons in the spinal cord of the chicken. I.
      Development and analysis of catecholamine synthesis capabilities.
AB  - 1. The development of tyrosine hydroxylase-immunoreactive (TH-IR) neurons was
      examined in the spinal cord of the chick embryo and hatchling. 2. Two groups of
      TH-IR cells are described, both of which appear to reach their full complement in
      number relatively late in embryonic development. One group is comprised of
      numerous cells located ventral to the central canal which make direct contact
      with the lumen of the canal. The other group consists of large multipolar neurons
      that reside in the dorsal horn, more commonly along the outer margin of the gray
      matter within lamina I and II, and less frequently deeper in the dorsal horn
      within medial portions of laminae V, VI or VII. 3. TH-IR cells ventral to the
      central canal in the chick are comparable in location to dopamine (DA)-containing
      spinal cord cells in lower vertebrate species. In contrast, the dorsally-suited
      TH-IR cells in the chick are known only to occur in similar positions in higher
      vertebrates. Therefore, the chick is novel in that the presence of both groups of
      TH-IR cells appearing together in significant numbers within the spinal cord has
      not been shown in any other species studied to date. 4. The TH-containing cells
      in the chick cord do not appear to contain the catecholamine biosynthesis
      enzymes, DBH or PNMT. Moreover, using anti-DA immunocytochemistry, neither group
      of TH-IR cells demonstrated detectable levels of DA in control animals nor in
      animals pretreated with inhibitors of MAO (MAO-I). 5. However, a difference was
      noted though between the two TH-IR cell groups in terms of their responses to
      exogenously supplied L-DOPA, the immediate precursor to DA. With the
      administration of L-DOPA and a MAO-I to chick hatchlings, cells in the region
      ventral to the central canal stained intensely for DA. In contrast, the same
      treatment failed to produce DA-immunoreactive cells in the dorsal horn. 6. One
      reasonable hypothesis for these results is that the TH-IR cells ventral to the
      central canal contain an active form of AADC, the enzyme that converts L-DOPA to
      DA. With this interpretation, if these cells can produce DA from L-DOPA, yet do
      not appear to synthesize DA endogenously, it would appear that the TH enzyme
      contained in these cells occurs in an inactive form. Whether the TH enzyme in the
      dorsally located immunoreactive cells is also inactive is uncertain since it
      remains unclear whether they contain AADC.

PMID- 9013030
TI  - Evidence for site selection during synaptogenesis: the surface distribution of
      synaptic sites in photoreceptor terminals of the files Musca and Drosophila.
AB  - 1. Photoreceptor terminals in the flies Musca domestica and Drosophila
      melanogaster have been reconstructed in three dimensions from serial EM to reveal
      the surface distributions of afferent tetrad synapses. 2. The terminals are
      cylindrical and surround two target cells; they have synaptic sites distributed
      along their length and around their circumference, except for a strip along the
      face that lies furthest away from the target cells. 3. Over their inner faces,
      the terminals have presynaptic sites that are distributed evenly. 4. The
      distribution of sites in maps plotted from reconstructed membrane surfaces was
      examined by quadrat analyses. The frequency of sites per quadrat division was not
      Poissonian, i.e. was non-random. Thus, some form of site selection must exist
      during synaptogenesis. 5. The sites were shown by variance ratio analysis to be
      regular (evenly dispersed, not clustered). This suggests that some form of
      interaction exists, so as to reduce the probability that a synapse will form
      close to an already existing synaptic site. 6. Distances between nearest
      neighbour pairs of synapses had a closest minimum spacing of about 0.8 micron in
      Musca that was violated by about 5% of pairs, whereas the corresponding distances
      were about 0.2 micron shorter in Drosophila, which had 13% of pairs situated
      closer together than 0.8 micron. 7. During synaptogenesis, either initially in
      the pupa or later in the adult, the probability that a synapse will form is
      therefore effectively zero within these distances from an existing synaptic site,
      perhaps through an inhibitory influence exerted by the latter. The nearest
      neighbour distances are normally distributed. 8. Unlike the distribution of
      presynaptic sites, the distribution of postsynaptic sites over the surfaces of
      the dendrites of the target cells is not even. Although not studied in detail,
      the corresponding nearest-neighbour distances are much smaller, as little as 0.1
      micron. Thus the wider spacing seen between sites over the receptor terminals is
      a function of the presynaptic cells, and not of their postsynaptic partners, and
      implies the existence of interactions between synaptic sites.

PMID- 9013039
TI  - Thyroid xenografts from patients with Graves' disease in severe combined
      immunodeficient mice and NIH-beige-nude-xid mice.
AB  - OBJECTIVE: To compare human thyroid xenografts from patients with Graves' disease
      in severe combined immunodeficient (SCID) mice and triple immunodeficient NIH
      beige-nude-xid (NIH-3) mice to obtain an improved animal model for studying these
      xenografts. DESIGN: Animal study. PARTICIPANTS AND ANIMALS: Patients with Graves'
      disease; SCID and NIH-3 mice. INTERVENTIONS: Thyroid tissue from six patients
      with Graves' disease was xenografted to SCID and NIH-3 mice; in addition,
      peripheral blood mononuclear cells (PBMC) from 12 patients with Graves' disease
      were grafted intraperitoneally to separate SCID and NIH-3 mice. OUTCOME MEASURES:
      Levels of human immunoglobulin (IgG), thyroperoxidase antibodies (TPO-Ab),
      thyroglobulin (Tg-Ab), and expression of thyrocyte intercellular adhesion
      molecule-1 (ICAM-1) and histocompatibility leukocyte antigen (HLA-DR) in mice
      after xenografting. RESULTS: IgG was detected in all mice grafted with Graves'
      thyroid tissue and some mice grafted with PBMC; levels of human IgG peaked 6 to
      10 weeks after xenografting. Human IgG levels reached a mean of 500 mg/L
      (standard error of the mean [SEM] 150 mg/L) in the NIH-3 mice with thyroid
      xenografts. This was similar to results in SCID mice with thyroid xenografts,
      which had a mean level of human IgG of 640 mg/L (SEM 230 mg/L). PBMC xenografting
      resulted in a mean IgG level of 1200 mg/L (SEM 250 mg/L) in NIH-3 mice, which was
      similar to the mean level of 1000 mg/L (SEM 280 mg/L) in SCID mice. The rate of
      rise in human IgG in the sera of the NIH-3 mice with thyroid xenografts was
      similar to that in the SCID mice. TPO-Ab were also detected in some mice with
      Graves' thyroid grafts and in a few mice injected with PBMC, with levels peaking
      4 to 6 weeks after xenografting. TPO-Ab levels reached a mean 109.3 U/mL (SEM
      57.2 U/mL) in the NIH mice with thyroid xenografts, which were similar to the
      mean level of 91.7 U/mL (SEM 34.2 U/mL) in the SCID mice. There were no
      significant differences in the Tg-Ab levels in each type of mice (13.9 [SEM 12.1]
      U/mL v. 17.9 [SEM 7.9] U/mL). Eight weeks after xenografting into mice, the
      expression of xenograft thyrocyte ICAM-1 decreased significantly in both the SCID
      and NIH-3 mice (from 43.4%, SEM 4.9%, to 35.9%, SEM 4.6%, in the NIH-3 mice, p <
      0.05, and from 43.4%. SEM 4.9%, to 32.5%, SEM 5.2%, in the SCID mice, p < 0.05).
      However, the expression of thyrocyte HLA-DR did not change significantly in the
      NIH-3 mice (from 11.5%, SEM 3.3%, to 10.8%, SEM 3.3%), whereas it decreased
      significantly in the SCID mice (from 11.5%, SEM 3.3%, to 4.2%, SEM 2.0%, p <
      0.02). CONCLUSIONS: Not only SCID mice but also NIH-3 mice may be useful as
      animal models for xenografted thyroid tissue, which will help us elucidate the
      pathogenesis of autoimmune thyroid disease. NIH-3 mice are superior to SCID mice
      in maintaining the expression of thyrocyte HLA-DR in Graves' thyroid xenografts
      at levels as high as those before xenografting; this maintenance of expression
      may be due to the lack of natural killer cells in NIH-3 mice.

PMID- 9013031
TI  - Modulation and selection of neurotransmitter responses during synapse formation
      between identified leech neurons.
AB  - 1. Serotonin (5-HT) modulates two different responses in the pressure sensitive
      neurons (P) of the leech: an inhibitory, Cl- dependent synaptic response and a
      depolarizing extrasynaptic response. 2. Serotonergic Retzius cells (R) in vivo
      and in culture elicit inhibitory Cl- dependent responses in P neurons. Moreover,
      at discrete sites of contact between R and P cells, the excitatory response to 5
      HT is gradually lost prior to synapse formation. This phenomenon is specifically
      mediated by R cells. 3. The extrasynaptic response is mediated by cation channels
      sensitive to protein kinase C (PKC). Cation channels are present at the sites of
      contact but they become insensitive to PKC. Moreover, cation channels from single
      P cells are no longer modulated by PKC if they are inserted (by cramming the
      patch pipette) into the cytoplasm of a P cell in contact with an R cell. 4.
      Blockers of tyrosine kinases prevent the uncoupling of cation channel modulation
      and inhibit synapse formation between the R and the P neurons. 5. We suggest that
      cell contact induces an intracellular, tyrosine kinase-dependent signal as part
      of the mechanism of neuronal recognition leading to synapse formation.

PMID- 9013040
TI  - Effective water clearance and tonicity balance: the excretion of water revisited.
AB  - OBJECTIVE: To demonstrate (1) that hyponatremia is usually due to an
      inappropriately low rate of excretion of electrolyte-free water and (2) that the
      measure "effective water clearance" (EWC) provides better information about renal
      defence of the body tonicity than does the classic measure free-water clearance,
      and to provide the rationale for calculating a "tonicity balance," which involves
      using water and sodium plus potassium intakes and their renal excretion to reveal
      the basis for changes in body tonicity. DESIGN: Prospective study. PARTICIPANTS:
      Four normal subjects with no conditions affecting excretion, 10 patients with
      advanced congestive heart failure (CHF) and 5 patients with the syndrome of
      inappropriate antidiuretic hormone secretion (SIADH). INTERVENTION: Normals and
      patients were administered a standard water load (20 mL per kg of body weight)
      during 45 minutes, and blood and urine samples were taken before, during and
      after the load was given. MAIN OUTCOME MEASURES: Urine and blood sodium and
      potassium concentrations, osmolar clearance, free-water clearance, electrolyte
      clearance and EWC. RESULTS: The water load was excreted rapidly by normals, more
      slowly by patients with CHF, and not at all by patients with SIADH. The EWC was
      positive in normals and those with CHF, but negative in those with SIADH. In
      patients with CHF, the EWC, but not the free-water clearance, helped explain why
      hyponatremia was corrected after the water load was given. CONCLUSIONS: In
      subjects with abnormal water excretion, the EWC provides the physiologic
      explanation for the renal role in variations in natremia. The authors propose a
      bedside evaluation of renal water and electrolyte handling that takes into
      consideration the role of urinary potassium in body tonicity. Changes in body
      tonicity can be explained by a "tonicity balance," a calculation in which the
      source and the net balance of sodium, potassium and water are considered.

PMID- 9013041
TI  - Arterial wall mechanical characteristics after treatment in collagenase: an in
      vitro aneurysm model.
AB  - OBJECTIVE: To investigate the mechanical characteristics of canine aortas treated
      with buffered collagenase as a first step in developing an animal model of aortic
      aneurysm for the validation of stent-grafts. DESIGN: In vitro study of canine
      aortas. INTERVENTIONS: Canine thoraco-abdominal arteries were divided into the
      descending thoracic aorta the suprarenal artery and the infrarenal artery; these
      segments were incubated separately in a buffered collagenase solution for 1 to 6
      hours. Some segments were left untreated as controls. OUTCOME MEASURES: Mean
      arterial wall thickness, measured with Vernier callipers and computerized
      histomorphometric methods and longitudinal tensile strength of control and
      treated vessel segments. RESULTS: The arterial wall thickness decreased with
      incubation time. After 1 hour of incubation the reduction was approximately 15%
      for the descending thoracic aorta, 16% for the suprarenal artery and 18% for the
      infrarenal artery. After 6 hours the total reduction in wall thickness was 32%,
      41% and 44% respectively for the 3 segments. The tensile strength of the treated
      arterial segments also decreased with the incubation period. Initially, the
      infrarenal segment displayed the greatest strength; however, this was reversed as
      the period of incubation increased. The inelastic limit of the descending
      thoracic aorta control segment was reached at 100% elongation, whereas that of
      the suprarenal artery was reached at 80% and that of the infrarenal artery was
      reached at 60% elongation. All of the arterial segments became weaker as the
      period of incubation in buffered collagenase increased. CONCLUSION: This in vitro
      incubation technique successfully altered the structure of the collagen fibre
      network within the arterial wall. This method may be an option in developing an
      aneurysm model to test stent-grafts in vivo.

PMID- 9013043
TI  - Unravelling a complex trait: the genetics of insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM), also known as type 1 or juvenile
      diabetes, is one of the first disorders with a complex genetic basis that
      researchers have begun to unravel. More than 20 years ago, the HLA region was
      found to contain a major locus that influences predisposition to IDDM, and a
      decade ago a locus with a smaller effect was identified in the insulin-gene
      region. With the advent of numerous microsatellite markers suitable for genome
      screening, an additional 6 loci that influence susceptibility to IDDM have been
      reported since late 1994. This paper summarizes that progress, with particular
      emphasis on research conducted by Field and associates. Some of the new loci
      appear to predispose people to IDDM independently of HLA and may be important
      factors in families with IDDM who lack strong HLA susceptibility. Other loci may
      interact to cause susceptibility, and specific combinations may be especially
      diabetogenic. Although isolating the actual predisposing genes in IDDM is more
      difficult than isolating those involved in single-locus genetic disorders, the
      fact that the genes can be identified with the use of a reasonable number of
      families is very encouraging for future research on other genetically complex
      disorders.

PMID- 9013042
TI  - Adaptation of the rectal wall to distension in children with constipation.
AB  - OBJECTIVE: To determine whether there is significant change in the tension-length
      relationship of the digestive smooth-muscle mechanical function in constipation
      in children and to examine a new method of analysis of the mechanical properties
      of the rectal wall. DESIGN: Case-control study. PARTICIPANTS: Thirty children
      with constipation and 30 control children who did not have constipation.
      INTERVENTION: Rapid distension of the rectal wall by inflation of a rectal
      balloon with air. MAIN OUTCOME MEASURES: The in vivo rectal pressure-volume
      P[t,V] curve was determined according to the quasilinear viscoelasticity law. The
      recorded pressure was defined as the product of 2 functions: the elastic response
      P0[V] and the reduced relaxation function G[t], a normalized function of time
      such that P[t,V] = P0[V] x G[t]. Analysis of variance with repeated measures and
      modelling (linear for P0[V] and exponential plus constant term for G[t] were used
      for data analysis. RESULTS: The quasilinear viscoelastic law can be applied to
      the in vivo determination of the mechanical properties of the rectal wall in
      controls and in children with constipation. The elastic response was similar in
      the 2 groups. The reduced relaxation function was significantly different between
      the 2 groups, with the absence of an asymptotic value in the group with
      constipation (p < 0.01). CONCLUSION: Distension of the rectal wall with the use
      of an air-inflated balloon, with this type of interpretation according to the
      viscoelastic law, is useful in the analysis of chronic constipation.

PMID- 9013044
TI  - Autoantibodies: diagnostic fingerprints and etiologic perplexities.
AB  - Autoantibodies are a hallmark of systemic rheumatic diseases, organ-specific
      autoimmune diseases and paraneoplastic syndromes. Cell biologists have used
      autoantibodies as probes to define the structure and function of novel
      macromolecules and to determine the chromosomal location of their respective
      genes. The observation that many autoantibodies appear before the clinical
      expression of disease suggests that they are not epiphenomena. Some
      autoantibodies are disease-specific markers and are in aid to establishing a
      diagnosis. Although it has been difficult to link autoantibodies to pathogenesis,
      they can be used to predict disease progression and outcome. For example,
      autoantibodies directed against topoisomerase are associated with progression of
      scleroderma to diffuse skin involvement and severe systemic disease, whereas
      antibodies to centromere proteins predict a more slowly progressive disease and
      development of a limited variant of scleroderma. Certain models of autoantibody
      production hold promise of a clearer understanding of the mechanisms that
      underlie autoimmunity. Drugs such as procainamide and hydralazine induce the
      production of chromatin autoantibodies. Exposure to heavy metals (e.g., mercury)
      is also linked to the development of autoantibodies. The data provide evidence
      that the autoimmune response is driven by autoantigens, which are multimolecular
      complexes involved in essential cellular functions.

PMID- 9013045
TI  - Long term changes in patients with hypsarrhythmia-infantile spasms: 505 patients,
      up to 43 years follow-up.
AB  - This study involved 505 patients with the EEG pattern of hypsarrhythmia (H) and
      clinical attacks of infantile spasms (IS) studied over a 51 year period from 1945
      until 1996. The total number of EEGs was 1300 and changes in the EEG and type of
      clinical seizure were followed for up to 43 yrs in a given patient. Although H
      and IS usually occur together in a given patient, 15% showed a disparity between
      the electrographic and clinical pattern, usually within a 6-12 mo period. The
      duration of H was usually < 1 mo but lasted as long as 7 yrs. The duration was
      dependent in part on the onset age and a very early onset of < 2 mo was
      associated with a short-lasting H and generally a good prognosis, as was an onset
      of 8-12 mo. Slightly more than half of these patients had an onset age of > 1 yr,
      likely in part related to a relatively large number studied before the
      introduction of the measles, mumps, and rubella vaccine. The next pattern after H
      was usually around 3 yrs of age, often focal discharges on the occipital or
      temporal areas or bilateral spike and wave complexes. The major changes in the
      EEG over time were the progressive increase in bilateral spike and wave complexes
      and temporal lobe discharges, in addition to an increase in other focal
      discharges at 6-9 yrs of age. Slow waves on the temporal areas and diffuse
      slowing became prominent in adulthood. The types of clinical attacks that became
      prominent in adulthood were generalized tonic-clonic and complex partial
      seizures. Other types of seizures most often occurred between the late teens and
      early 20's with absence attacks seen especially at 8-10 yrs of age.

PMID- 9013046
TI  - Obstructive sleep apnea and abnormal P300 latency topography.
AB  - This study was conducted to evaluate cognitive abnormalities in obstructive sleep
      apnea (OSA) using cognitive evoked potentials (P300), and to clarify if such
      cognitive dysfunction is related to the OSA itself or to the hypersomnolence in
      OSA. Subjects were administered a polysomnogram, auditory and visual P300 testing
      using 31 scalp electrodes, and the multiple sleep latency test. There were 40
      normal subjects ages 26 to 75. Of 143 consecutive OSA patients ages 26 to 75, 56
      had severe OSA (Respiratory Disturbance Index or RDI 40-80/h sleep) with
      objective somnolence (Mean Sleep Latency < 5 min). Thirty-three had severe OSA
      without objective somnolence. Fifty-four had profound OSA (RDI > 80/h sleep) with
      or without objective somnolence. The normals and the three OSA groups did not
      differ in age. Patients with profound OSA or with severe OSA without somnolence
      had longer visual P300 latency than normals. The groups also differed in visual
      P300 latency topography. OSA patients had significantly longer latencies
      frontally than normals. Thus, OSA, even in the absence of hypersomnolence, is
      associated with abnormalities in cognitive evoked potentials. Visual P300 latency
      at frontal electrodes seems to be a neurophysiological index of dysfunction in
      OSA that is independent of tests of sleepiness.

PMID- 9013047
TI  - Early and middle latency evoked potentials in medically and psychiatrically
      normal daily marihuana users: a paucity of significant findings.
AB  - The use of evoked potentials to study CNS effects of marihuana (THC) have
      produced inconsistent findings. Our previous pilot studies suggested that
      auditory P300 latencies and amplitudes, auditory P50 and somatosensory P30
      amplitudes and brainstem auditory evoked potential latencies were altered in THC
      users. Because these findings were flawed by uncontrolled psychiatric diagnostic
      and medication variables, we undertook a controlled investigation of screened
      medically and psychiatrically normal THC users and controls. When age effects
      were controlled, THC related alterations of brain stem and both auditory and
      visual P300 responses could not be seen. This report extends our analyses to
      other auditory, somatosensory and visual evoked potentials. With the possible
      exception of an elevated auditory P50 amplitude, significant evoked potential
      correlates to daily THC use were not seen when normals were studied and age
      effects controlled.

PMID- 9013048
TI  - Event-related potential and intelligence test performance of 50 patients with
      epilepsy.
AB  - The findings of P300 and Wechsler Adult Intelligence Scale in 50 epileptic
      patients were assessed and compared with those of 38 healthy adult volunteers.
      The relationships between the course of epilepsy and the WAIS or peak P300
      latencies were analyzed. Results showed that the prolonged latencies of P300 were
      positively correlated with course of epilepsy but not with full scale IQ. P300
      peak latency and Arithmetic, Digit Symbol and Picture Arrangement were closely
      related.

PMID- 9013049
TI  - Unusual EEG theta rhythms over central region in Rett syndrome: considerations of
      the underlying dysfunction.
AB  - In 10 female patients (age 2-26 years) with clinical evidence of Rett Syndrome
      (RS), unusual and prominent rhythmical theta activity (4-5/sec or 5-6/sec) proved
      to be the outstanding EEG feature. This pattern was present in waking state
      and/or sleep. When it was noted in the waking state, the localization (vertex,
      central region and vicinity) and blocking responses to active or passive
      movements suggested a slow equivalent of Rolandic mu rhythm (in two patients
      associated with a posterior 10-12/sec alpha rhythm). In sleep, rhythmical theta
      activity was either Rolandic or more diffuse, sometimes independently occurring
      with central spikes. The prominent rhythmical 4-5/sec or 5-6/sec activity and its
      relationship to Rolandic mu rhythm suggest a dysfunction of the motor cortex in
      RS. This would be congruent with the frequent observation of central spikes. EEG
      evidence of motor cortex dysfunction might be helpful in the understanding of
      this enigmatic disorder and conducive to the following hypothesis: RS is
      characterized by motor cortical dyscontrol due to primary frontal lobe
      dysfunction. The usefulness of EEG, however, is limited to insights into the
      (secondary) motor-cortex dysfunction.

PMID- 9013050
TI  - Rhythmic slow activity in benign childhood epilepsy with centrotemporal spikes.
AB  - In benign childhood epilepsy with centrotemporal spikes (BCECT), focal rhythmic
      slow EEG activity is occasionally observed in the same region where the
      centrotemporal spikes or Rolandic Discharges (RD) are seen. This slowing appears
      especially when RDs are frequent. Holmes therefore hypothesized that these slow
      waves in BCECT were not the manifestations of structural lesion of the brain but
      secondary slowing accompanying RD. In order to clarify the origin of the slow
      activity, clonazepam was administered to four BCECT patients who had the focal
      slow waves. Clonazepam has recently been found by us to selectively diminish RD
      in BCECT. After the administration of clonazepam for 4 consecutive weeks, not
      only RDs but also the slow activity disappeared completely. This finding strongly
      suggests that these focal rhythmic slow waves in the same region of the RD are a
      part of the morphology of RD.

PMID- 9013051
TI  - Frontal midline theta rhythm in young healthy adults.
AB  - In this study, we examined the relationship between the frontal midline (Fm)
      theta rhythm that appears when a healthy subject is engaged in mental tasks and
      the theta rhythm which appears in the frontal region of healthy subjects during
      light drowsiness. The samples for this study were obtained from 465 EEGs of
      healthy Japan Air Self Defense Force personnel. The 39 who had frontal theta
      rhythm during light drowsiness were selected to be included in the theta group.
      For the control group, 34 subjects were randomly selected from the remaining 426
      without frontal theta rhythm. When these subjects were reexamined, the rate of
      appearance of the frontal midline theta rhythm which appears during light
      drowsiness was 87.2% in the theta group and 0% in the control group. The rate of
      appearance of the Fm theta was 94.9% in the theta group and 3.0% in the control
      group. The two types of frontal theta rhythms closely resembled each other in
      frequency (94.6%) and distribution (83.8%). Except for the results of the
      hypomania (Ma) scores, there was no remarkable difference between the two groups
      when the MMPI was administered. The results of our study suggest that there is a
      close correlation between the frontal theta rhythm that appears during light
      drowsiness and the Fm theta.

PMID- 9013052
TI  - Partial seizures associated with cisplatin administration: a case report.
AB  - A 49-year-old man was treated with cisplatin and pirarubicin for tongue cancer.
      After the second course of chemotherapy, partial seizures including transient
      motor aphasia, tonic finger movement, and loss of consciousness were observed.
      The EEG showed frequent diffuse (multiple) spike and slow wave discharges.
      Following the administration of carbamazepine and diazepam, no seizures occurred
      and no paroxysmal discharges were observed or EEGs. We conclude that
      carbamazepine and diazepam administration was effective.

PMID- 9013053
TI  - The efficacy and tolerance of mifepristone and prostaglandin in termination of
      pregnancy of less than 63 days gestation; UK Multicentre Study--final results.
AB  - This paper summarizes the final results of an open multicenter study in 13
      hospital gynecological units in Scotland and England. In the study, 1018 pregnant
      women with up to 9 week amenorrhoea received 600 mg oral mifepristone followed 48
      h later by vaginal gemeprost 1 mg for the induction of first trimester abortion.
      Outcome was measured by assessment of the frequency of complete abortion or the
      need for subsequent surgical evacuation. Tolerance was assessed in terms of pain,
      requirement for analgesia, bleeding, and other adverse effects. There was
      complete abortion in 94.8% (95%CI 93.4-96.2); surgical evacuation was performed
      in 5.2% of patients. There was no relationship between outcome and age of
      gestation on the day mifepristone was given. Seven women were given a
      transfusion. Narcotic analgesia was administered after gemeprost to 38.1% of
      nullipara and 10.7% of multipara. Mifepristone and prostaglandin is an effective
      and acceptable alternative to surgical termination of pregnancy in the early
      first trimester.

PMID- 9013054
TI  - Effect of Norplant implants on the pituitary-adrenal axis function and reserve
      capacity.
AB  - The present work investigated the effects of Norplant implants on the pituitary
      adrenal function among 15 users of Norplant implants prior to and 6 months after
      insertion of the implants. Serum cortisol levels and their diurnal variations,
      ACTH and 24-h urinary 17-ketosteroids, ketogenic steroids, 17-hydroxy steroids,
      and creatinine, were measured. Also, a dynamic test (the 5-h Synacthen depot =
      ACTH stimulation test) was done before and 6 months after implants insertion. The
      9 a.m. cortisol levels were blunted (within the normal ranges) while the 6 p.m.
      values were unaltered. The 24-h urinary ketogenic, hydroxy, and ketosteroids were
      also unchanged after Norplant implants use. The ACTH stimulation test showed a
      decreased adrenal response which was also within normal ranges. These data should
      raise the question related to suprarenal response to acute or prolonged stresses,
      such as surgical operations or shock in women using Norplant implants.

PMID- 9013055
TI  - Increased number of induced abortions in Norway after media coverage of adverse
      vascular events from the use of third-generation oral contraceptives.
AB  - After the press release in Lancet (October 18, 1995) of increased risks for
      adverse vascular events in users of pills containing desogestrel and gestodene
      the total sales of oral contraceptives dropped over a two-month period by 17%,
      while sales of the only desogestrel brand available (Marvelon) dropped by over
      70% in Norway. From sales, we can estimate that more than 45,000 women either
      changed from Marvelon to a second or first-generation brand or stopped using OCs.
      In total, more than 25,000 women discontinued OC use in Norway during November
      and December of 1995. Abortion data from one Norwegian county, representing 6-7%
      of the Norwegian population, show no statistically significant changes in the
      total number of induced abortions from the first quarter of 1996 as compared with
      that of the first quarter in preceding years. However, abortion rates that had
      been steadily decreasing from 1992 through 1995 in women 24 years old or younger,
      were promptly interrupted by a significant 36% increase during the first quarter
      of 1996. Most of the additional cases were found among single, childless
      students. The observed increased abortion rate among younger women is most
      probably linked to changes in contraceptive use during the pill scare of the late
      October through December of 1995, during which time these women conceived.

PMID- 9013056
TI  - Contraceptive practices of women requesting termination of pregnancy: a study
      from China.
AB  - In order to develop a program for prevention of unwanted pregnancies, we
      conducted a survey of contraceptive practices and reasons for contraceptive
      failures of 1520 women seeking abortion at eight large hospitals in Zheng Zhou
      City, Henan Province, P.R. China, during the period from March 1996 to May 1996.
      The most frequent cause of the unplanned pregnancy was contraceptive failure
      (71.9%) 61.7% (938) of these current pregnancies were potentially predictable by
      virtue of nonuse of contraception (427) or by recognition of contraceptive
      failures (511). Among the contraceptive failures, the proportion of condom
      mishaps was the highest (29.7%), next was IUD failures (23.5%), then rhythm
      miscalculation (15.9%). Most of abortion seekers (77.1%) used some contraceptive
      methods previously. But only 19.7% of them used a contraceptive method at the
      first sexual intercourse. Among 1520 abortion seekers. 57.6% had used condoms
      previously; 50.9% of the condom users had at least one instance of condom mishap.
      The rhythm method had been used by 31.7% of abortion seekers previously; 59.1% of
      the rhythm users had at least one instance of rhythm failure. Of the 16.8% of
      abortion seekers who had used pills, 58.0% of them had pill failures Among condom
      and pill failures, most of them (46.4% condom users and 56.0%, pill users)
      belonged to the users failure category (poor compliance). Of those seeking
      abortion 56.4% had experienced at least one instance of previous abortion; 5.3%
      had experienced previous abortions at least two times. Emergency contraception
      had been utilized by only 10 subjects prior to this current pregnancy.

PMID- 9013057
TI  - Endometrial glandular proliferation and estrogen receptor content during the
      normal menstrual cycle.
AB  - Hysterectomy specimens from 35 normally cycling premenopausal women were examined
      to determine the relationship of endometrial glandular proliferation to estrogen
      receptor content. The cases were divided into follicular phase (n = 20), early
      luteal phase, days 1-5 post ovulation (n = 5) and mid to late luteal phase (n =
      10). Proliferation rates, as determined by MIB-1 expression, were maximal in the
      endometrial functionalis during the follicular phase (701 cells/1000), decreased
      by half during the early luteal phase (327 cells/1000), and virtually ceased
      during the mid to late luteal phase (8 cells/1000) (p < 0.001). Estrogen receptor
      status, determined immunohistochemically and graded on a scale of 0 to 4+,
      averaged 3.4+, 2.2+ and 0.5+ during the follicular, early luteal, and mid to late
      luteal phases, respectively, in the endometrial functionalis (p < 0.001).
      Proliferation rates in the endometrial basalis paralleled those in the
      functionalis, but at a lower rate, whereas estrogen receptor expression underwent
      considerably less cyclical variation. We conclude that estrogen receptor status
      shows a highly significant correlation with glandular proliferation rates and are
      predictive of endometrial proliferative changes during the normal menstrual
      cycle.

PMID- 9013058
TI  - Biodegradable norethindrone (NET:cholesterol) contraceptive implants: phase II-A:
      a clinical study in women.
AB  - Safety, contraceptive efficacy and biodegradability of subdermal norethindrone
      (NET)-cholesterol implants (Anuelle) were investigated in 19 healthy, sexually
      active women. Mean serum NET levels in women with four and five pellets,
      containing 174 mg and 266.5 mg NET, showed a "burst-effect" of 3.17 and 3.71
      ng/ml, respectively, within 24 h post implantation. Subsequently, for the four-
      and five-pellet groups, respectively, the levels declined from 0.75 to 0.40 ng/ml
      and 1.05 to 0.61 ng/ml during the months 12-15, from 0.40 to 0.11 ng/ml and 0.61
      to 0.25 ng/ml up to month 36. The serum NET levels were undetectable at 36 months
      and beyond, indicating complete biodegradability of NET pellets. Serum E2 levels
      remained within normal limits (> 50 pg/ml), whereas serum P indicated anovulatory
      cycles in 78% of the four-pellet group and 99% of the five-pellet group. FSH and
      LH levels were subnormal and acyclic. Plasma lipids showed reduced total and LDL
      cholesterol and triglycerides. HDL cholesterol remained unchanged. Drug-related
      adverse effects were essentially limited to irregular bleeding. There were no
      pregnancies in either group.

PMID- 9013059
TI  - Comparative effectiveness of three antiprogestins alone and in combination with
      anordiol in terminating pregnancy in the rat.
AB  - The effectiveness of mifepristone, onapristone, and ORG 31806 alone or in
      combination with anordiol to terminate pregnancy in the rat was evaluated. ORG
      31806 at a dose of 2 mg/kg/day, mifepristone at 4 mg/kg/day, and onapristone at 8
      mg/kg/day, terminated pregnancy in all treated animals. Anordiol, an
      antiestrogen, at a dose of 5 mg/kg/day, terminated pregnancy in all treated
      animals. Anordiol acted synergistically with all three antiprogestins terminating
      pregnancy in the rat. The antiprogestins at doses that were either partially
      effective or non-effective became 100% effective when administered with a non
      effective dose of anordiol. Thus, combination of ORG 31806 (1 mg/kg/day) plus
      anordiol (0.31 mg/kg/ day), mifepristone (1 mg/kg/day) plus anordiol (0.62 mg/
      kg/day), and onapristone (2 mg/kg/day) plus anordiol (2.5 mg/kg/day) terminated
      pregnancy in all treated animals. These combinations of the antiprogestins and
      anordiol decreased significantly the serum progesterone levels but not serum 17
      beta-estradiol levels. The present results indicate that the most potent
      combination was ORG 31806 plus anordiol.

PMID- 9013060
TI  - Reversible changes in the content of cellular and microtubular tubulin in
      spermatogenic cells after gossypol treatment.
AB  - After exposure of young male rats to gossypol acetic acid for various times, a
      reduction in the content of cellular and microtubular beta-tubulin was found in
      spermatocytes and spermatids. The content of tubulin was measured by enzyme
      linked immunosorbent assay (ELISA). The results were expressed as micrograms
      tubulin/100 micrograms total protein and compared with those of the control rats.
      After drug treatment for 2, 6, 12, and 20 weeks, the content of total cell
      tubulin in spermatocyte was reduced by 2.4%. 8.8%. 52%, and 61%, respectively,
      whereas the content of tubulin in spermatid was reduced by 7.4%, 36%, 70%, and
      72%, respectively. At the same time length of drug treatment, the content of
      microtubular tubulin in spermatocyte was reduced by 1.6% 13%, 58% and 61% in
      comparison to the reduction rate of 5%, 37%, 69%, and 77%, respectively, for
      spermatid. These results indicated that the tubulin associated with spermatids
      were more vulnerable to gossypol than that of the spermatocytes. Eight weeks
      after withdrawal of the drug treatment, the content of tubulin in spermatocytes
      and spermatids was recovered.

PMID- 9013061
TI  - Study of the pharmacokinetic interaction between ethinylestradiol and amoxicillin
      in rabbits.
AB  - Several antibiotics have been implicated in oral contraception failure when they
      are administered at the same time as the oral contraceptive (OC) pill. In the
      present paper, a study about amoxicillin-ethinylestradiol (EE2) pharmacokinetic
      potential interaction was studied. Two rabbit groups were utilized, the first
      group received amoxicillin (10 mg/kg) and EE2 (30, 50 and 100 micrograms/kg,
      respectively), both by intravenous (i.v.) route. The second group received
      amoxicillin (oral route, 10 mg/kg/day) and EE2 (i.v. route, 100 mu/kg) on day 1,
      4 and 8 of antibiotic treatment, respectively. After compartmental (two
      compartment open model) and non-compartmental analysis of plasma concentrations,
      the statistical study (ANOVA p < or = 0.05) revealed that the presence of
      amoxicillin did not modify the EE2 distribution and elimination pharmacokinetic
      parameters (by comparison with those obtained in a previous study where EE2 was
      administered alone). There also were no significant differences with the time of
      amoxicillin oral treatment.

PMID- 9013062
TI  - Evaluation of the prethrombotic state.

PMID- 9013063
TI  - Thoracic sonography for diagnosis and intervention.
AB  - Many physicians believe that ultrasound has limited usefulness in chest disease.
      Our clinical experiences and a review of the literature in preparation for this
      monograph have convinced us that sonography can be a very useful and versatile
      tool for thoracic diagnosis and intervention. Although there are some limitations
      caused by interposed ribs and air-containing lung, almost all of the compartments
      of the chest can be evaluated with ultrasound, which gives unique and clinically
      useful information. Ultrasound guidance for biopsy and drainage does take some
      time to learn, but we feel that the effort is very worthwhile. The same
      advantages ultrasound enjoys for other body regions make it a modality that will
      see increased use in the chest as well. We hope that this monograph will
      stimulate our colleagues to explore and expand upon the techniques described.

PMID- 9013064
TI  - The prevention and management of the angry back (excited skin syndrome [ESS]) in
      patch testing: Part II.

PMID- 9013065
TI  - Human phenotypes. The atopic and seborrheic: Part II.

PMID- 9013066
TI  - Dermatophagia: "wolf-biter".
AB  - Dermatophagia is a neurodermatitis akin to onychophagia, onychotillomania,
      trichotillomania, dermatothlasia, neurotic excoriations, and other conditions in
      which persons have a neurotic habit or compulsion to self-multilate their skin or
      its appendages. Dermatophagia is a habit or compulsion, consciously or
      subconsciously, to bite one's own skin. We believe "dermatophagia" is a more
      appropriate term for this disorder than the descriptive term "wolf-biter".

PMID- 9013067
TI  - Malassezia furfur: a fungus belonging to the physiological skin flora and its
      relevance in skin disorders.
AB  - Malassezia furfur is an anthropophilic fungus that belongs to the physiological
      skin flora. The fungus can grow in a yeast phase as well as in a mycelial phase;
      on nonaffected skin the fungus is mainly prevalent in the yeast phase. The
      organism has complex lipid requirements for growth, which also explains its
      occurrence on the skin. This also leads to the requirement for specially
      supplemented media for in vitro cultivation. Malassezia furfur is the causative
      agent of pityriasis versicolor. It also seems to be associated with seborrheic
      dermatitis and dandruff formation, folliculitis, confluent and reticulate
      papillomatosis, and the provocation of psoriatic lesions. Many substances for
      topical application, such as azole antimycotics, ciclopirox olamine, piroctone
      olamine, zinc pyrithione, or sulfur-containing substances are effective in the
      treatment of these diseases. In recent years rare cases of systemic infections
      and fungemias caused by Malassezia have been reported.

PMID- 9013068
TI  - Indeterminate cell histiocytosis treated successfully with 2
      chlorodeoxyadenosine.
AB  - We report the case of a 54-year-old man with a ten-year history of a generalized
      papular eruption consistent with the diagnosis of indeterminate cell
      histiocytosis. The patient responded favorably to a course of treatment with 2
      chlorodeoxyadenosine.

PMID- 9013069
TI  - Concept of total care: a third dimension in the treatment of psoriasis.

PMID- 9013070
TI  - Severe folliculitis with keloid scars induced by wax epilation in adolescents.
AB  - Wax epilation is a popular and generally safe technique used to remove unwanted
      body hair. We describe two adolescent girls who sustained severe folliculitis
      following wax epilation. Despite treatment with systemic antibiotics and local
      treatment, their rash evolved to severe permanent keloid scars. We suggest that
      parents and adolescents should be advised to perform wax epilation in optimal
      hygienic conditions. Physicians should be aware of this possible sequela and
      treat it rapidly and aggressively, with both topical and systemic agents, to
      avert complications.

PMID- 9013071
TI  - Pigmented sweat gland tumor mimicking melanoma.
AB  - Eccrine poroma, a common adnexal neoplasm, usually presents as a solitary,
      smooth, flesh-colored nodule on the foot or hand. Eccrine porocarcinoma is
      extremely rare and much more variable in its morphology and location. Both tumors
      can contain melanocytes and melanin. We describe a patient with an enlarging,
      eroded brownish black nodule on his shoulder. Examination of a biopsy specimen
      showed it to be derived from acrosyringium and to contain abundant melanin and
      scattered dendritic melanocytes. Eccrine poroma and porocarcinoma should be
      considered in the clinical differential diagnosis of pigmented tumors.

PMID- 9013072
TI  - Islet cell autoimmunity in women with gestational diabetes and risk of
      progression to insulin-dependent diabetes mellitus.

PMID- 9013073
TI  - Review of gestational diabetes mellitus and low-calorie diet and physical
      exercise as therapy.

PMID- 9013074
TI  - Transforming growth factor beta in diabetic nephropathy.

PMID- 9013075
TI  - Food-induced type 1 diabetes in the BB rat.

PMID- 9013076
TI  - Islet cell transplantation: beyond the paradigms.

PMID- 9013077
TI  - Physiology and pathophysiology of aquaporins.

PMID- 9013078
TI  - Identification of steroid receptors in human adipose tissue.
AB  - Steroids have the ability to alter adipose tissue distribution. Controversy
      exists as to whether these effects of sex hormones (oestrogen, progesterone and
      testosterone) on human adipose tissue are indirect or direct, as only very few
      studies have focused on steroid receptor status in human adipose tissue. In the
      present study, we reinvestigated steroid receptor status in human mature adipose
      tissue and human preadipocytes. Oestrogen, glucocorticoid and androgen receptors
      were found in human mature adipocytes from both women and men. The receptors were
      detected by ligand binding. Furthermore, the existence of the receptors was
      confirmed by demonstrating that adipocytes contained mRNA encoding the receptors.
      cDNA was generated using reverse transcriptase (RT) followed by polymerase chain
      reaction (PCR) amplification using specific primers (RT-PCR) for the specific
      steroid receptors. Adipocytes did not contain mRNA encoding the progesterone
      receptor (PR), and no progesterone binding was detectable in human adipocytes.
      Human preadipocytes contained glucocorticoid receptor (GR) mRNA and androgen
      receptor (AR) mRNA, whereas we were unable to detect oestrogen receptor (ER) mRNA
      and progesterone mRNA in human preadipocytes. In conclusion, oestrogen
      glucocorticoid and androgen receptors are present in mature adipocytes from
      subjects of both sexes, whereas adipocytes do not contain progesterone receptors.
      In preadipocytes, only glucocorticoid receptors and androgen receptors are
      present, whereas oestrogen receptors and progesterone receptors are not present.

PMID- 9013079
TI  - Biosynthesis of prostacyclin and thromboxane A2 during chronic hypoxaemia in
      children with cyanotic congenital heart disease.
AB  - The high risk of vaso-occlusive events in children younger than 4 years with
      cyanotic congenital heart disease and polycythaemia has been attributed to
      increased thromboxane (Tx) A2 formation. In older children with cyanotic
      congenital heart disease, however, the risk of vaso-occlusive events is much
      lower. We therefore hypothesized that the formation of TxA2 and prostacyclin is
      not disturbed in this age group. We measured urinary excretion of stable index
      metabolites of in vivo TxA2 and prostacyclin formation by gas chromatography-mass
      spectrometry in nine children (age 5.9-14.4, median 8.7 years) with cyanotic
      congenital heart disease, and in nine healthy, age-matched control subjects. The
      patients excreted less 2,3-dinor-TxB2 (systemic TxA2 formation, P = 0.03), 2,3
      dinor-6-keto-PGF1 alpha (systemic prostacyclin formation. P = 0.03) and TxB2
      (renal TxA2 formation, P = 0.01) than the control subjects. We conclude that in
      children older than 5 years with cyanotic congenital heart disease, endogenous
      synthesis of TxA2 and prostacyclin is not stimulated. This result may explain the
      lower risk of vaso-occlusive events in this age group as compared with younger
      children. In addition, our results suggest that chronic hypoxaemia may affect the
      in vivo formation of TxA2 and prostacyclin and the metabolic disposition of TxB2.

PMID- 9013080
TI  - Effect of hormone replacement therapy on the susceptibility of low-density
      lipoprotein to oxidation among postmenopausal hypercholesterolaemic women.
AB  - The effect of sequential combined hormone replacement therapy on the
      susceptibility of low-density lipoprotein to oxidative modification was
      investigated in a double-blind, randomized placebo-controlled study.
      Hypercholesterolaemic, postmenopausal women were supplemented with 17 beta
      oestradiol and norethisterone acetate (n = 13 subjects) or placebo capsules (n =
      15 subjects) for 12 weeks. They were instructed to follow the American Heart
      Association step one diet. Low-density lipoprotein, isolated before and after
      treatment, was subjected to copper-catalysed lipid peroxidation. There were no
      significant differences between low-density lipoprotein from the hormone
      replacement therapy and placebo groups, as assessed by measuring the lag time for
      formation of conjugated dienes, the rate of formation and the amount of
      conjugated dienes formed, the amount of lipid peroxides generated, and the
      relative electrophoretic mobility at baseline and after treatment. Dietary
      records showed that the subjects were consuming similar amounts of fat and
      vitamins. No major differences were found in the fatty acid pattern of low
      density lipoprotein from the two groups. In conclusion, the results indicated
      that hormone replacement therapy with 17 beta-oestradiol sequentially combined
      with norethisterone acetate in non-smoking, hypercholesterolaemic, postmenopausal
      women has no protective effect on the susceptibility of low-density lipoprotein
      to copper-catalysed modification in vitro.

PMID- 9013081
TI  - Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and
      replication.
AB  - The Phyllanthus amarus plant shows potential for treating hepatitis B virus. To
      define the mechanism of action of P. amarus, we used HepG2 2.2.15 cells, which
      support hepatitis B virus replication. P. amarus inhibited hepatitis B virus
      polymerase activity, decreased episomal hepatitis B virus DNA content and
      suppressed virus release into culture medium. To examine transcriptional control
      mechanisms, we used G26 hepatitis B virus transgenic mice, which produce serum
      HBsAg but neither HBcAg nor virion particles. When P. amarus was administered to
      transgenic mice, hepatic HBsAg mRNA levels decreased, indicating transcriptional
      or post-transcriptional down-regulation of the transgene. Increase in hepatitis B
      virus mRNA expression after stimulation of the glucocorticoid responsive element
      was also suppressed by P. amarus, suggesting involvement of the hepatitis B virus
      enhancer in this response. Disruption by P. amarus of hepatitis B virus
      polymerase activity, mRNA transcription and replication supports its role as an
      antiviral agent.

PMID- 9013082
TI  - Diadenosine polyphosphates induce transplasma membrane calcium influx in cultured
      glomerular mesangial cells.
AB  - The effects of diadenosine tetraphosphate (AP4A) diadenosine pentaphosphate
      (AP5A) and diadenosine hexaphosphate (AP6A) on the cytosolic-free calcium
      concentration ([Ca2+]i) were evaluated in cultured rat glomerular mesangial cells
      (MCs) using the fluorescent dye technique. The addition of 10 mumol L-1 AP4A,
      AP5A or AP6A significantly increased [Ca2+]i in MCs by 57 +/- 9 nmol L-1 n = 17;
      P < 0.01), 76 +/- 27 nmol L-1 (n = 9; P < 0.01) or 65 +/- 12 nmol L-1 (n = 18; P
      < 0.01) respectively. In the absence of extracellular calcium, there was no
      significant change in [Ca2+]i in MCs after administration of diadenosine
      polyphosphates, indicating that these agents induce transplasma membrane Ca2+
      influx. AP6A significantly enhanced the angiotensin II-induced changes in [Ca2+]i
      in MCs. The AP5A-induced transplasma membrane Ca2+ influx was inhibited by the P2
      purinoceptor blockers suramin and pyridoxal-phosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS), but was not affected by the adenosine A1 receptor
      blocker 8-cyclopentyl-1.3-dipro-pylzanthine (CPDPX). Adenosine triphosphate (ATP)
      and adenosine 5'-O-(3-thio)triphosphate (ATP-gamma S) increased [Ca2+]i in MCs,
      whereas alpha, beta-methylene ATP had no effect on [Ca2+]i in MCs. Measurements
      of diacylglycerol and phosphatidic acid showed that AP5A and AP6A also stimulated
      phospholipase C, but had no effect on phospholipase D. The inhibition of
      phosphatidylcholine-specific phospholipase C significantly reduced the AP5A
      induced [Ca2+]i increase. In summary, diadenosine polyphosphates induce Ca2+
      influx through P2 purinoceptors and may be involved in the local regulation of
      vascular resistance evoked by the Ca(2+)-dependent contractile response of
      mesangial cells.

PMID- 9013083
TI  - Effects of isolated limb perfusion with tumour necrosis factor-alpha on the
      function of monocytes and T lymphocytes in patients with cancer.
AB  - The objective of the present study was to investigate the effects of isolated
      limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and melphalan
      in patients with cancer on, first, plasma levels of cytokines, second, systemic
      monocyte and T-lymphocyte distribution and, third, the ability of mononuclear
      cells to produce cytokines upon stimulation in vitro. Six patients undergoing an
      ILP were entered into the study (group 1). In addition, patients undergoing a
      major surgical operation (group 2) minor operation (group 3) as well as healthy
      volunteers (group 4) were included as control groups. Sensitive enzyme-linked
      immunosorbent assays (ELISAs) were used to measure TNF-alpha and interleukin-6
      (IL-6) plasma levels at various time points during and after operation.
      Furthermore, the percentage of monocytes and T lymphocytes was determined in all
      studied groups using a FACScan. In addition, cytokine production upon stimulation
      with lipopolysaccharide (LPS) and a combination of anti-CD3/anti-CD28 monoclonal
      antibodies in whole-blood cultures was investigated. Increased plasma levels of
      TNF-alpha and IL-6 in patients undergoing ILP was observed, but only IL-6
      appeared to be increased in patients treated with a major operation. No
      significant fluctuations were found in the other groups studied. Concerning the
      number of monocytes, a significant decrease was observed only in patients treated
      with ILP. Furthermore, a decreased production of TNF-alpha, IL-6 and IL-8 upon
      various types of stimulation in vitro was found in those patients, but also after
      a major operation. In conclusion, the results of the present study show increased
      plasma levels of cytokines in patients treated with ILP and major operation.
      Furthermore, a decrease in numbers of monocytes in the circulation and the
      ability of mononuclear cells to produce cytokines in vitro may be induced by
      administration of TNF-alpha in ILP. Although similar results were found in
      patients treated with major operation, the underlying mechanisms of this
      phenomenon remain to be elucidated.

PMID- 9013084
TI  - Molecular analysis of the T-cell receptor beta-chain repertoire in early
      rheumatoid arthritis: heterogeneous TCRBV gene usage with shared amino acid
      profiles in CDR3 regions of T lymphocytes in multiple synovial tissue needle
      biopsies from the same joint.
AB  - To gain insight into the nature of the immune response with respect to
      accumulation and composition of the T-cell receptor (TCR) repertoire in synovial
      tissue in rheumatoid arthritis (RA), we have determined the nucleotide sequence
      of TCRBV regions transcribed by T lymphocytes derived from synovial tissue.
      Synovial tissue was obtained by needle biopsies from three different sites of the
      same joint in two early RA patients. We found that the TCRBV region repertoire
      among synovial tissue-infiltrating mononuclear cells was heterogeneous when the
      different biopsies taken from each patient were compared. However, DNA sequence
      analysis of TCRBV rearrangements of synovial T lymphocytes showed conserved amino
      acid usage profiles in the CDR3 domains of different TCRBV regions, which
      exhibited an individual specific character. These CDR3 motifs were not present in
      paired samples of peripheral blood. The existence of homologous CDR3 amino acid
      profiles within the TCRBV regions derived from synovial tissue is indicative of
      an antigen-driven immune response.

PMID- 9013085
TI  - Helicobacter pylori and proteolytic activity.
AB  - Protease activity of 10 different H. pylori strains, purified marker proteases
      and protease-positive reference bacteria (Klebsiella ozaenae, Serratia
      marcescens) were tested against bovine haemoglobin, porcine mucin, bovine serum
      albumin, gelatin and casein as substrates. After incubation in development buffer
      and subsequent staining with Coomassie blue, protease activity bands were
      demonstrated as transparent spots after polyacrylamide gel electrophoresis (PAGE)
      on gels with incorporated substrate. Presence of protease activity was
      investigated in a wide pH range (pH 2.0-9.0). Although marker proteases (0.15-0.2
      microgram per slot) as well as protease-positive bacteria (2-30 micrograms per
      slot) clearly showed proteolytic activity in gels containing 0.1-0.2% protein mL
      1, no proteolytic activity was demonstrated in any of the H. pylori strains
      tested. This finding indicates that H. pylori does not possess significant
      protease activity, as this would have been detected by this sensitive method.

PMID- 9013086
TI  - To determine the effects of ultraviolet light, natural light and ionizing
      radiation on pyridinium cross-links in bone and urine using high-performance
      liquid chromatography.
AB  - The aims of the study were to characterize the denaturation of urinary free and
      conjugated pyridinoline (Pyr) and deoxypyridinoline (Dpyr) on exposure to
      ultraviolet (UV) and natural light at different pH levels and to study the
      effects of X- and gamma-irradiation on Pyr and Dpyr in urine and in the
      mineralized and non-mineralized compartments of human bone. Urine samples from
      six normal subjects, adjusted to pH 3.0, 7.0 and 9.0 were exposed to UV light for
      up to 3 days. Urine collections (2 mL and 24 h) from three subjects, pH adjusted
      to 1.0, 2.0, 3.0, 4.0 and 5.0, were exposed to natural light for up to 1 day.
      Urine samples and bone slices from seven human cadaveric femurs were irradiated
      with increasing doses of X-rays (0-100 Gy) and high-dose gamma-radiation (28
      kGy). Mineralized and non-mineralized bone were separated using a modification of
      a published method employing heat denaturation followed by trypsin hydrolysis and
      analysed for Pyr, Dpyr and hydroxyproline (Hypro). The rate of UV photolysis of
      urinary Pyr and Dpyr increased with pH and was faster in the free fraction (after
      3 days' exposure: free Pyr and Dpyr at pH 7.0 vs. 9.0, P < 0.05, conjugated pH
      3.0 vs. 9.0, P < 0.05). Exposure to natural light for 3 h did not significantly
      decrease urinary Pyr and Dpyr in either sample collections, but levels were
      reduced in the 2-mL aliquots after exposure for 1 day (P < 0.05). X-irradiation
      of urine and bone did not affect Pyr and Dpyr. Pyr content was similar in both
      bone compartments (Pyr/ Hypro = 0.12 +/- 0.004), but Dpyr was higher in the non
      mineralized compartment (Dpyr/Hypro = 0.047 +/- 0.002 vs. 0.038 +/- 0.002, P <
      0.001). UV light and gamma-irradiation result in denaturation of pyridinium cross
      links in urine. These cross-links are present in both the mineralized and non
      mineralized bone compartments but are not affected by the doses of gamma
      irradiation that denature these cross-links in urine.

PMID- 9013087
TI  - Polymorphism of the apolipoprotein A-IV gene and its significance in lipid
      metabolism and coronary heart disease in a Japanese population.
AB  - Apolipoprotein A-IV (apo A-IV) is involved in the metabolism of both
      triglycerides and high-density lipoproteins (HDLs). Apo A-IV has been suggested
      as participating in several stages of reverse cholesterol transport. Uncertainty
      about the exact biochemical function of apo A-IV has made the use of genetic apo
      A-IV polymorphism (variants) attractive in evaluating its physiological role. To
      date, although some reports indicate that DNA polymorphisms at this locus play an
      important role in the metabolism of lipids and lipoproteins in western
      (Caucasian) populations, no similar comprehensive analysis has been performed in
      a distinct Japanese population. Using DNA sequencing and a restriction fragment
      length polymorphism (RFLP) study with polymerase chain reaction (PCR), the
      following allele frequencies were established: (a) codon -8 (G-->A, non
      synonymous) allele 2 = 0 (n = 105); (b) codon 9 (A-->G, synonymous) allele 2 =
      0.388 (n = 152); (c) codon 347 (A-->T, non-synonymous) allele 2 = 0 (n = 900);
      (d) codon 360 (T-->G, non-synonymous) allele 2 = 0 (n = 800); (e) VNTR exon 3
      [(CTGT)3 and (CTGT)4] (CTGT)3 = 0.262 (n = 105); and (f) MspI (newly detected
      polymorphic site) polymorphism (C C/T GG) within intron 2, allele 2 = 0.096 (n =
      193). The frequencies of these polymorphisms, except for that of the newly
      identified MspI site, are completely different from those reported in western
      populations. Among the 900 subjects examined, we found one ACT (Thr) to ACG (Thr)
      synonymous mutation at codon 347, which does not change the primary structure of
      apo A-IV. The apo A-IV allele frequency in patients (166 men and 56 women) with
      angiographically proven coronary heart disease (CHD) was also studied [codon 9
      allele 2 = 0.329 (n = 217); VNTR exon 3 (CTGT)3 = 0.262 (n = 84); MspI within
      intron 2, allele 2 = 0.092 (n = 222)]. Furthermore, we evaluated serum lipid and
      lipoprotein levels quantitatively in control subjects and Japanese CHD patients.
      These polymorphisms did not show any consistent and significant association with
      lipid and lipoprotein parameters. In addition, no gender-specific effects of apo
      A-IV polymorphisms on lipid parameters adjusted for confounding factors were
      observed in either CHD patients or control subjects. Our results indicate that
      the apo A-IV gene is not a major determinant of the risk for CHD in Japanese.

PMID- 9013088
TI  - Different effects of continuous oestrogen-progestin and transdermal oestrogen
      with cyclic progestin regimens on low-density lipoprotein subclasses.
AB  - Seventy-five postmenopausal women were randomly allocated to receive either
      continuous oral 17 beta-oestradiol 2 mg day-1 and norethisterone acetate 1 mg day
      1 (E2/NETA) or transdermal treatment consisting of 28-day cycles with patches
      delivering 17 beta-oestradiol 50 micrograms day-1 combined with oral cyclic
      medroxyprogesterone acetate 10 mg day-1, on days 17-28 (E2/MPA). At baseline, the
      plasma lipid and lipoprotein concentrations, composition and concentrations of
      low-density lipoprotein (LDL) subclasses (LDL1, LDL2 and LDL3) isolated by
      density-gradient ultracentrifugation were similar in the two groups. The post
      heparin plasma hepatic lipase activity (HL) correlated inversely with the
      percentage of total LDL found in LDL1 (buoyant LDL) and directly with the
      percentage of LDL found in LDL3 (dense LDL). After 12 months of hormone
      replacement therapy (HRT), the total and LDL-cholesterol concentration of the E2/
      NETA group decreased by 14% and 17% respectively (P < 0.001), while in the E2/MPA
      group these parameters remained unchanged. The lowering of LDL-cholesterol in the
      E2/NETA group was a consequence of a significant reduction of the large, buoyant
      LDL particles (LDL1) from 103 mg dL-1 to 60 mg dl-1 (P < 0.001) and of a decrease
      of cholesterol content of LDL particles in the major LDL subclass, LDL2. In the
      E2/MPA group, the concentration of LDL1 decreased, but less than in the oral
      group. In both groups, a significant increase in the concentration of the LDL3
      subclass was observed, indicating an overall shift to denser LDL particles. After
      12 months, the post-heparin plasma HL activity decreased only in the E2/NETA
      group (by 12%). The inverse correlation between post-heparin plasma HL activity
      and LDL1 persisted in both groups, but the direct correlation between HL and LDL3
      vanished in the E2/NETA group and subsided in the E2/MPA group. Our results
      indicate that HRT has multiple effects on LDL subclasses and suggest that these
      changes cannot be explained by changes in HL activity.

PMID- 9013089
TI  - Screening and characterization of specific anti-lipopolysaccharide antibodies in
      Belgian blood donors by enzyme-linked immunosorbent assays.
AB  - The goal of this project was to find and collect high concentrations of endotoxin
      specific antibodies for therapeutic IgG- or IgM-enriched preparations. Various
      enzyme-linked immunosorbent assays (ELISAs) were developed to perform
      longitudinal studies of the serological response to a large panel of smooth and
      rough purified lipopolysaccharide (LPS) extracts in a population of healthy blood
      donors. To accomplish this, 1612 human serum samples from volunteer blood donors
      collected by seven different blood banks in Belgium were screened and specific
      IgM and IgG activities were measured. Approximately 17% of the donors had anti
      LPS concentrations higher than 40 mg L-1. Of these, 10.9% had anti-smooth LPS
      antibodies, 3.7% had anti-rough LPS antibodies and 2.8% were found to be positive
      towards both types of LPS. The mean anti-LPS antibody concentration was 8 mg L-1
      for rough LPS and 14 mg L-1 for smooth LPS. Age- and sex-related distributions of
      the activities indicated that the greatest prevalence of high anti-LPS
      concentration was in women aged 40-49 years and in men older than 60 years.
      Differential absorption experiments showed that the pooled serum of selected
      blood donors contained a mixture of specific and cross-reacting antibodies. We
      detected predominantly anti-LPS activities due to the IgG1 and IgG2 subclasses.
      The range of specificities to different LPS was increased by the pooling of
      selected sera. It was concluded that pools of naturally occurring specific anti
      LPS immunoglobulin antibodies may be obtained in Belgium by screening blood
      donors using ELISAs that we have developed.

PMID- 9013090
TI  - Effects of insulin treatment on endoneurial and systemic oxidative stress in
      relation to nerve conduction in streptozotocin-diabetic rats.
AB  - As increased oxidative stress is probably a pathogenetic factor in the
      development of diabetic complications, we studied nerve function and endogenous
      antioxidants in plasma, erythrocytes and sciatic nerve of untreated and insulin
      treated streptozotocin-diabetic rats. After 18 weeks, the diabetes-induced
      sciatic nerve conduction velocity deficits were approximately 65% improved by
      insulin (P < 0.001). Plasma superoxide dismutase was significantly reduced in
      diabetes (P < 0.01); smaller decreases in plasma catalase and glutathione levels
      were observed. These changes were corrected by insulin treatment. In
      erythrocytes, decreased superoxide dismutase (P < 0.05) and increased total
      glutathione levels (P < 0.05) were found. All effects of diabetes, including a
      rise in plasma malonyldialdehyde (P < 0.05), were partially reversed by insulin
      treatment. In nervous tissue, diabetes caused increased catalase activity,
      uninfluenced by insulin (P < 0.05). Nerve superoxide dismutase and glutathione
      did not change. The data suggest that in diabetes, changes in systemic rather
      than endoneurial oxidative stress lead to nerve dysfunction.

PMID- 9013091
TI  - Lipid profile in patients with microvascular angina.
AB  - Lipid, lipoprotein and apolipoprotein levels, as well as the susceptibility of
      low-density lipoprotein (LDL) to oxidation, were studied in patients with micro
      vascular angina in comparison with patients with coronary artery disease (CAD)
      and normal subjects. Total cholesterol, LDL-cholesterol and apolipoprotein B
      levels in microvascular angina patients (235 +/- 46 mg dL-1, 135 +/- 33 mg dL-1
      and 146 +/- 32 mg dL-1 respectively) were significantly higher than in control
      subjects (204 +/- 40 mg dL-1, 116 +/- 35 mg dL-1 and 129 +/- 29 mg dL-1
      respectively, P < 0.01). These parameters were also significantly higher in CAD
      patients than in control subjects. By contrast, high-density lipoprotein (HDL)
      cholesterol levels in microvascular angina patients were no different from those
      in control subjects, although both were significantly higher than in the CAD
      patients (48 +/- 16 mg dL-1 and 45 +/- 12 mg dL-1 compared with 40 +/- 10 mg dL
      1, P < 0.01 and P < 0.05 respectively). Similar results were obtained for the
      apolipoprotein AI levels. Furthermore, the atherogenic risk ratio, LDL
      cholesterol/HDL-cholesterol, in microvascular angina patients was significantly
      lower than in the CAD patients (3.4 +/- 1.2 vs. 4.1 +/- 1.5 respectively, P <
      0.01). Median (range) serum lipoprotein (a) [Lp(a)] levels in microvascular
      angina patients and CAD patients [13 mg dL-1 (0.8-92) and 16 mg dL-1 (0.8-96)
      respectively] were significantly higher than in control subjects [7 mg-dL-1 (0.8
      44)], P < 0.01 and P < 0.005 respectively. Sigmoidal curves and electrophoretic
      mobility of the Cu(2+)-oxidized LDL in both microvascular angina and CAD patients
      were not significantly different from those of control subjects. Finally, no
      significant differences were found between groups in total triglyceride levels or
      in very low-density lipoprotein (VLDL), LDL and HDL triglyceride levels. Our
      results show that the microvascular angina patients exhibit lipid abnormalities
      similar to those observed in CAD patients, with the important exception of the
      HDL-cholesterol and apolipoprotein AI levels, which are significantly higher in
      microvascular angina patients. We suggest that the abnormal cholesterol and Lp(a)
      levels may be involved in the pathophysiology of microvascular angina by
      affecting endothelial function and endothelium-mediated vasodilator responses,
      whereas the higher HDL levels may be a factor contributing to the absence of
      angiographically documented CAD in microvascular angina patients.

PMID- 9013092
TI  - Gastric mucosal phospholipids in dogs with familial stomatocytosis-hypertrophic
      gastritis.
AB  - In dogs, hypertrophic gastritis, which resembles Menetrier's disease in man, has
      been demonstrated to be part of a hereditary syndrome called familial
      stomatocytosis-hypertrophic gastritis. In addition to hypertrophic gastritis,
      affected dogs exhibit abnormal blood phospholipid composition. Phospholipids may
      play a role in maintaining gastric mucosal integrity, and this may be compromised
      in gastritis. The question arises whether the differences in blood phospholipids
      may result from a disorder that might also be revealed in the composition of
      gastric mucosal phospholipids. We analysed the phospholipid composition of
      gastric mucosa from four dogs with familial stomatocytosis-hypertrophic
      gastritis. The general phospholipid composition and the molecular composition of
      phosphatidylcholine from mucosal tissue in the corpus of the stomach where
      hypertrophic gastritis was evident were not different from that of the antrum,
      where the tissue was normal. These results do not corroborate a relation between
      the gastric mucosal phospholipid composition and hypertrophic gastritis.

PMID- 9013093
TI  - Changes in biliary lipid output after interruption of pravastatin treatment in
      humans.
AB  - The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      (e.g. pravastatin) has gradually increased in the treatment of
      hypercholesterolaemia. By inhibiting HMG-CoA reductase (the rate-limiting enzyme
      in cholesterol synthesis) activity, cholesterol synthesis in the liver is reduced
      and the plasma level of cholesterol, especially low-density lipoprotein (LDL)
      cholesterol, is substantially lowered. Simultaneously, inhibition of HMG CoA
      reductase activity is associated with increased synthesis and accumulation of
      larger amounts of HMG CoA reductase enzyme protein. The main purpose of this
      study was to determine if the cessation of pravastatin treatment causes a rapid
      increase in the synthesis and biliary secretion of cholesterol, a condition which
      might lead to a temporarily increased cholesterol saturation of bile. Nine
      patients undergoing surgery for stones in the common bile duct were fitted with T
      tubes in the common bile duct peroperatively; the side arm of the T-tube was left
      open postoperatively, creating a biliary fistula. All patients were given 6 days'
      treatment with pravastatin (20 mg b.i.d.) following the operation. Bile was
      collected from the T-tube, in 12-h fractions during this period and for another 3
      days after termination of the treatment. Plasma levels of lipoproteins and
      lathosterol--reflecting cholesterol synthesis--were determined on several
      occasions. After cessation of pravastatin treatment, the plasma levels of total
      cholesterol and LDL-cholesterol increased by 21% and 33% respectively. High
      density lipoprotein (HDL)-cholesterol did not change. The plasma level of
      lathosterol was increased two- to fourfold. Outputs of bile acids and
      phospholipids were significantly increased (23% and 10% respectively) after
      termination of treatment, whereas the output of cholesterol was not significantly
      changed. Cholesterol saturation was reduced by 20%, from 175 +/- 37% to 140 +/-
      19%, but this change was not significant. The results indicate that, with the
      present experimental model (biliary diversion), the synthesis and biliary
      secretion of bile acids seem to be largely dependent on the de novo synthesis of
      cholesterol in the liver, whereas the biliary output of cholesterol is not.

PMID- 9013094
TI  - Imaging of Ca(2+)-induced cytoplasmic Ca2+ responses in normal and pathological
      parathyroid cells.
AB  - Ca(2+)-induced changes in the cytoplasmic Ca2+ concentration ([Ca2+]i) were
      studied in bovine and normal and pathological human parathyroid cells using
      digital image analysis of fura-2-loaded cells. When raising external Ca2+ from
      0.5 to 3.0 mmol L-1, about 95% of all cells reacted rapidly and simultaneously
      with sustained elevation of [Ca2+]i. In approximately two out of three bovine
      parathyroid cells, normal human cells and cells from most patients with
      hyperparathyroidism (HPT) the sustained phase was preceded by an overshooting
      [Ca2+]i transient. The proportion of cells, with such a transient was decreased
      in cells from severe cases of uraemic parathyroid hyperplasia only. However,
      pathological human cells from adenomas and normal-sized glands associated with
      adenomas, as well as cells from primary and uraemic hyperplasias, had lower peak
      and sustained levels than normal human and bovine cells. The results indicate
      that both normal and pathological parathyroid cells exhibit heterogeneity in
      their [Ca2+]i responses to elevation of external Ca2+. The Ca(2+)-induced [Ca2+]i
      transients and the sustained elevations are attenuated in pathological human
      parathyroid cells. However, the presence of the overshooting transient represents
      physiological variability rather than being a consequence of the pathophysiology
      associated with HPT.

PMID- 9013095
TI  - Development and exacerbation of oral lichen planus during and after interferon
      therapy for hepatitis C.
AB  - Oral lichen planus (OLP) is frequently seen in patients with hepatitis C virus
      (HCV) infection. To clarify the role of HCV in OLP pathogenesis, we investigated
      the occurrence and progression of oral lesions in chronic hepatitis C patients
      treated with interferon. Oral surgeons examined 24 hepatitis C patients (15 men,
      nine women; mean age 48.1 years) for oral lesions before, during and after
      interferon (IFN) treatment. OLP was observed in 16.7% (4/24). Two patients had
      OLP before treatment, one during and one after treatment. Those who developed OLP
      during or after treatment had neither improvement nor disappearance of OLP even
      when serum HCV RNA became negative. Leucoplakia was seen in four patients before
      treatment and oral cancer in one patient 6 months after completing treatment. OLP
      can occur, exacerbate and persist during IFN treatment for hepatitis C, even when
      serum HCV RNA becomes negative. The present study suggested that OLP pathogenesis
      in hepatitis C is due to host factors induced by HCV infection rather than direct
      HCV participation. Treating physicians should be aware of OLP occurrence or
      exacerbation by IFN treatment with hepatitis C patients, but IFN therapy is not
      necessarily contraindicated in these patients.

PMID- 9013097
TI  - Maternal plasma levels of vascular endothelial growth factor in normotensive
      pregnancies and in pregnancies complicated by pre-eclampsia.
AB  - We have measured the level of vascular endothelial growth factor (VEGF) in
      maternal plasma during normotensive pregnancy and in pregnancies complicated by
      pre-eclampsia. VEGF was measured using a competitive enzyme immunoassay. Plasma
      VEGF was significantly elevated (P < 0.0001) in the pre-eclamptic group (median
      value 32.7 ng mL-1, range 10.3-64.0), compared with the normotensive group
      (median value 11.7 ng mL-1, range 6.3-24.3). VEGF is a potent regulator of
      endothelial cell function. The increased level found in women with pre-eclampsia
      indicates that VEGF may be involved in the maternal endothelial cell dysfunction
      associated with this condition. An increase in VEGF, a potent regulator of
      microvascular permeability, may also contribute to the extravasation of plasma
      proteins and the subsequent development of proteinuria, both characteristic
      features of pre-eclampsia.

PMID- 9013096
TI  - The influence of growth hormone substitution therapy on erythroid and myeloid
      progenitor cells and on peripheral blood cells in adult patients with growth
      hormone deficiency.
AB  - It has been reported that hypophysectomized rats exhibit normochromic, normocytic
      anaemia. Pancytopenia with impaired DNA synthesis in the bone marrow can be
      restored in these hypophysectomized rats by syngeneic pituitary grafts placed
      under the kidney capsule or treatment with growth hormone (GH). Until now, adults
      with hypopituitarism have received adequate replacement therapy with thyroxine,
      cortisol and sex steroids, but not with GH. We therefore investigated the effects
      of GH replacement therapy on the proliferation and differentiation of erythroid
      and myeloid progenitor and peripheral blood cells in 11 adult patients with
      growth hormone deficiency in a double-blind, placebo-controlled study for the
      first 6 months of therapy. The placebo group showed no changes during the first 6
      months without therapy in either insulin-like growth factor I (IGF-I) levels,
      erythroid and myeloid progenitor precursor cells or peripheral blood cells. After
      commencement of GH therapy, IGF-I levels rose significantly during 24 months of
      therapy from 75.3 +/- 13.5 to 225 +/- 34.7 ng mL-1 (P < 0.001). Erythroid and
      myeloid progenitor precursor cells showed a steep and significant increase after
      18 and 24 months of therapy (erythroid: from 10.7 +/- 3.5 to 261.4 +/- 79.8, P <
      0.02, after 18 months and to 276.8 +/- 149.8 x 10(5) mononuclear cell colonies, P
      < 0.03, after 24 months; granulocyte-macrophage colony-forming units: from 39.7
      +/- 9.8 to 316.9 +/- 124.6, P < 0.002, after 18 months and to 366 +/- 188.7 x
      10(5) mononuclear cell colonies, P < 0.03, after 24 months), whereas the
      peripheral red and white blood cells exhibited only minimal non-significant
      changes. The principal regulators of erythropoiesis, such as erythropoietin, and
      parameters reflecting erythropoiesis in the peripheral blood, such as
      reticulocytes, remained almost unchanged throughout the whole study period. We
      therefore conclude that patients with GH deficiency do not have anaemia, but have
      haematopoietic precursor cells in the lower normal range, and that GH
      substitution therapy over a period of 24 months has a marked effect on erythroid
      and myeloid progenitor precursor cells but only negligible effects on peripheral
      blood cells in GH-deficient adults.

PMID- 9013098
TI  - Profound decrease of in vivo formation of thromboxane during oestrogen therapy.
AB  - Oestrogen has been proposed to influence platelet activity and formation of the
      vasoactive eicosanoids thromboxane and prostacyclin. Previous studies have been
      based on ex vivo techniques with well-known artifacts during blood sampling and
      ex vivo conditions. The present study is the first to assess in vivo formation
      through gas chromatographic/mass spectrometric analysis of the major urinary
      metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha. Ten
      consecutive male patients with prostatic carcinoma participating in a randomized
      study comparing the effects of parenteral oestrogen therapy (n = 5) with
      orchidectomy (n = 5) were included. Oestrogen was given as polyestradiol
      phosphate 240 mg i.m. every month, 2,3-dinor thromboxane B2 and 2,3-dinor-6-keto
      PGF1 alpha were analysed with the help of tetradeuterated internal
      carriers/standards. We found a consistent decrease of in vivo formation of
      thromboxane by approximately 40% during parenteral oestrogen therapy (P = 0.008)
      and a doubling after surgical castration. The ratio of prostacyclin to
      thromboxane increased by approximately 50% (P = 0.023) during oestrogen therapy.
      In conclusion, oestrogen induced a marked decrease of in vivo formation of
      thromboxane and a marked increase in the ratio of prostacyclin to thromboxane
      formation in all patients. According to current knowledge this should be
      beneficial for the cardiovascular system. Furthermore, thromboxane formation
      increased after surgical castration. The latter fact should direct attention to
      the influence of androgens on thromboxane synthesis. Our findings discloses a
      marked sex-hormone sensitivity of the thromboxane-forming system.

PMID- 9013099
TI  - Improved distribution of pulmonary flush solution to the tracheobronchial wall in
      pulmonary transplantation.
AB  - This report describes the experimental results obtained with conventional
      (pulmonary artery, PA) flushing versus retrograde perfusion (via left atrium, LA)
      using 99mTc-labeled macroaggregated albumin (MAA-99mTc) to ascertain the
      distribution throughout the tracheobronchial (TB) tree in 10 Large-White pigs.
      Lung preservation was achieved with 4 degrees C Euro-Collins solution (60 ml/kg)
      instilled via PA (n = 5) or LA (n = 5). Simultaneously, MAA-99mTc was given using
      the same respective route and the isotope uptake quantified at different TB
      levels after heart-lung block harvest and dissection of all tissue adjacent to
      TB: proximal and distal trachea and right and left main bronchi. Retrograde
      distribution resulted in a significantly higher 99mTc count compared to the PA
      route (p < 0.01).

PMID- 9013100
TI  - Influence of the perfusate temperature on lung preservation: is there an optimum?
AB  - The optimal temperature of the pulmonary flush perfusate is still a matter of
      controversy. At present, a temperature of 10 degrees C is favored. This study
      deals with the structural and functional impact of different perfusate
      temperatures on lung preservation. In an extracorporeal rat heart-lung model
      lungs were preserved with Perfadex solution of 4, 15 and 25 degrees C and
      submitted to 2 h ischemia. Heart-lung blocks harvested from male rats were
      perfused with Krebs-Henseleit solution and ventilated with room air. Lungs were
      perfused with deoxygenated perfusate via the working right ventricle while the
      coronary arteries were retrogradely perfused with oxygenated perfusate.
      Oxygenation capacity (dPO2), peak inspiratory pressure (PIP) and pulmonary
      vascular resistance were measured. After establishment of baseline functional
      parameters hearts were arrested with 10 ml St. Thomas cardioplegia and lungs were
      flushed with 20 ml Perfadex solution. The heart-lung block was then stored for 2
      h at 10 degrees C. Reperfusion was performed thereafter under the same
      conditions. At the end of the trial the lung tissue water was measured by the
      wet/dry ratio. The perfusion time of the groups flushed with 15 or 25 degrees C
      perfusate was significantly lower than that of the 4 degrees C group. After 20
      min reperfusion dPO2 of the groups flushed with 15 or 25 degrees C was superior
      to those submitted to a 4 degrees C flush perfusion. PIP was significantly lower
      in the 15 degrees C group than in the 4 and 25 degrees C groups. The wet/dry
      ratio revealed the smallest water content in the 15 degrees C group. We conclude
      that the post-ischemic lung function is dependent on the temperature of the flush
      perfusate. Among the tested temperatures, perfusion at 15 degrees C showed the
      best results. The optimum may therefore lie in this range.

PMID- 9013101
TI  - Detection of acute rejection by 133Xe radiospirometry after single lung
      transplantation in an experimental porcine model.
AB  - Aim of this experimental study was to evaluate acute rejection in a porcine
      single-lung transplantation model by using 133Xe radiospirometry. Left lung
      allotransplantation was performed on 11 and autotransplantation on 5 piglets.
      Postoperative monitoring consisted of 77 radiospirometric examinations with
      assessments of regional perfusion (Qtx), ventilation (V) and
      ventilation/perfusion ratio (V/Qtx). Results were compared with transbronchial
      biopsy. A significant decrease in Qtx (p < 0.01) and an increase in V/Qtx (p <
      0.01) were observed during acute rejection, whereas V remained unaltered. These
      changes were significant already at minimal rejection (grade A1), and further
      increased at moderate rejection (grade A3). Sensitivity and specificity of Qtx
      were 82 and 74%, and those of V/Qtx, 87 and 65%. 133Xe radiospirometry detects
      even minimal acute rejection after single lung transplantation.

PMID- 9013102
TI  - Maldistribution of multidose blood cardioplegia: pharmacologic intervention to
      prevent subendocardial hypoperfusion by alpha-adrenergic blockade.
AB  - Maldistribution of multidose blood cardioplegia (BCP) continues to be a problem
      causing perioperative subendocardial damage. However, it is not known whether
      alpha-adrenergic stimulation contributes to the maldistribution of multidose BCP.
      We have evaluated the effects of phenoxybenzamine (POB) on multidose BCP
      distribution, with a right heart bypass model in 14 dogs. Although gradual
      increases in coronary vascular resistance (CVR) were noted in the control group
      (CP-1: 0.53 +/- 0.08, CP-2: 0.57 +/- 0.07, CP-3: 0.78 +/- 0.10 mm Hg/ml/min/100
      g), there was no significant rise in CVR in the POB group (CP-1: 0.36 +/- 0.03,
      CP-2: 0.37 +/- 0.04, CP-3: 0.42 +/- 0.04 mm Hg/ml/min/100 g). Improved delivery
      of BCP was observed in the POB group during CP-3 (endo/epicardial flow ratio 1.72
      +/- 0.07 vs. 1.21 +/- 0.18 in the control group; p < 0.05). These data indicate
      that improved delivery of BCP can be obtained by alpha-adrenergic blockade, if
      multiple injections of BCP are used for cardiac surgery.

PMID- 9013103
TI  - Cytokine levels after open and laparoscopic cholecystectomy.
AB  - A prospective study of serum cytokine levels was performed in patients randomly
      assigned to undergo either laparoscopic cholecystectomy (LC) or open
      cholecystectomy (OC). The kinetics of serum interleukin-1 beta (IL-1 beta),
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL
      10), and cortisol were studied in both groups of patients. Cytokine and cortisol
      levels were measured in serum samples from patients who underwent either LC (n =
      14) or OC (n = 14) using enzyme-linked immunosorbent assay and radioimmunoassay,
      respectively. Serum samples were obtained 24 h before surgery and 24 h and 7 days
      after surgery. IL-6 levels differed significantly (p < 0.05) between the LC and
      OC groups. IL-1 beta, IL-10, TNF-alpha and cortisol levels showed no significant
      differences (p > 0.05). Kinetic studies of IL-6, IL-1 beta and TNF-alpha levels
      revealed them to behave similarly, 24 h after surgery the levels of these
      cytokines were higher than those 24 h before surgery. These levels normalized by
      7 days after surgery. Cytokine concentrations were always higher in the OC group
      than in the LC group. IL-1 beta and IL-10 levels were the most stable in both
      groups, though cortisol levels were also fairly stable.

PMID- 9013104
TI  - p53 overexpression and proliferative activity do not correlate with lymph node
      metastasis in early gastric cancer.
AB  - We investigated p53 overexpression and the proliferative activity of the primary
      lesion as well as the clinicopathological features of 75 patients with gastric
      cancer invading the submucosa (sm cancer), of whom 14 (18.7%) had lymph node
      metastasis. Among the clinicopathologic features studied, only lymphatic invasion
      by the primary tumor was related to lymph node metastasis. There was no
      relationship between immunohistochemical staining for p53 protein or Ki-67 and
      lymph node metastasis. The p53-positive rate was 35.7 and 57.1% in patients with
      and without metastasis, respectively, while the mean Ki-67 labeling index was
      38.9 and 38.1%, respectively. Our results suggest that p53 mutation or the
      proliferative activity of sm cancer do not influence lymph node metastasis, even
      though p53 mutation may enhance the proliferative activity and metastatic
      potential of advanced gastric cancer.

PMID- 9013105
TI  - Obturator internus muscle autotransfer: a new concept for the treatment of
      anismus. Clinical experience.
AB  - In this study 20 patients suffering from chronic constipation due to spastic anal
      sphincters were operated upon using a new surgical technique. The technique aimed
      at constructing an active anal dilator mechanism using the obturator internus
      muscles mobilized from both sides and sutured to the side wall of the anal canal
      in order to overcome the spastic anal sphincters during defaecation. This series
      included 3 failures (15%), 16 successful cases (80%), and 1 dissatisfied patient
      despite normal postoperative investigations (5%). Eleven patients (55%) showed
      immediate postoperative normalization of their defaecation. Five patients (25%)
      showed normalization of their defaecation after 10 sessions of electric
      stimulation of the transposed muscles given 1 month postoperatively for 10
      successive days. All the successful cases (16 patients) maintained their good
      results during the period of follow-up which ranged from 16 to 45 months (average
      = 30.31 months). For the successful cases, follow-up was from 16 to 42 months
      (average = 26.72 months). Immediate postoperative complications included 3 cases
      of wound infection and 2 cases of transient incontinence to gases which responded
      completely to postoperative Faradic stimulation. No cases of persistent
      incontinence of any degree were detected among the 20 patients studied. The 3
      failures were mainly due to avoidable technical problems. The technique was safe,
      easy, and physiological, using a strictly perineal approach.

PMID- 9013106
TI  - Physical, biological and handling characteristics of surgical suture material: a
      comparison of four different multifilament absorbable sutures.
AB  - OBJECTIVE: Four different braided absorbable surgical materials (Dexon, Dexon II
      Bicolor, Vicryl and Polysorb) 2/0 USP, which basically share the same
      indications, were studied in vitro and in vivo with regard to their physical
      properties as well as tissue compatibility and surgical handling. Analyzing the
      results the authors tried to determine the most useful suture in surgical
      practice. METHOD: Physical tests to determine tensile strength, knot-breaking
      strength and knot security were carried out. Additionally an in vivo model
      (Wistar rat) was used to compare histocompatibility and loss of function due to
      hydrolytic resorption. Furthermore, a handling test was carried out by trained
      surgeons. RESULTS: Polysorb had the highest linear tensile strength but also the
      fastest loss of function following tissue implantation, whereas Vicryl showed the
      slowest loss of function. Similar results were obtained with regard to the knot
      breaking strength. After pulsatile stressing Dexon II Bicolor and Dexon showed
      the highest irreversible elongation followed by Vicryl and Polysorb. Polysorb had
      the best knotting characteristics, scoring highest also in the handling study.
      CONCLUSIONS: The authors conclude that with Polysorb all features and properties
      of braided suture material have reached a high level of quality. This suture
      combines the positive characteristics of monofilament with those of multifilament
      materials, thus coming closest to being the 'optimal suture'.

PMID- 9013107
TI  - The Mayday distal first metatarsal osteotomy for hallux valgus: a review after
      the introduction of a new instrument.
AB  - We present the short-term follow-up of 55 symptomatic hallux valgus deformities
      in 38 patients, treated operatively with a modification of the spike distal first
      metatarsal osteotomy, as described by Gibson and Piggott in 1962. The age range
      of the patients was 17 to 72 years at the time of surgery. The postoperative
      follow-up period was 12 to 55 months. Excellent and good clinical and
      radiographic results were recorded in 96.2% of our patients. Two of the patients
      (3.8%) were dissatisfied; one of them complained of metatarsalgia after the
      procedure, and the other had stiffness of the metatarsophalangeal joint and
      metatarsalgia that had been present before surgery. Three others (5.45%) required
      revision after early postoperative displacement but were asymptomatic
      subsequently. We concluded that our technique is an effective method of treating
      mild hallux valgus deformities with the advantages of simplicity, no shortening
      of the first metatarsal, and no risk of dorsal tilting of the distal fragment.
      Hallux valgus (lateral deviation of the great toe) is not a single disorder, as
      the name implies, but a complex deformity of the first ray that sometimes may
      involve the lesser toes. More than 130 procedures exist for the surgical
      correction of hallux valgus, which means that no treatment is unique. No single
      operation is effective for all bunions. The objectives of surgical treatment are
      to reduce pain, to restore articular congruency, and to narrow the forefoot
      without impairing function, by transferring weight to the lesser metatarsals
      either by shortening or by dorsal tilting of the first metatarsal. Patient
      selection is important for a satisfactory outcome after surgery of any kind, and
      our criteria were age, degree of deformity, presence of arthrosis, and
      subluxation of the first metatarsophalangeal joint. In this study, we present a
      new method of treating hallux valgus that has been used at Mayday University
      Hospital since 1990. The technique was first described at the British Orthopaedic
      Foot Surgery Society, Liverpool, November 1990, and we now present the short-term
      follow-up results. The procedure is essentially a modification of the spike
      osteotomy of the neck of the first metatarsal, as described by Gibson and
      Piggott. It has the advantages of simplicity, no shortening of the first
      metatarsal, and no risk of dorsal displacement of the distal fragment.

PMID- 9013108
TI  - Mechanical behavior of the foot and ankle after plantar fascia release in the
      unstable foot.
AB  - The change in position of the bones of the foot was studied in three dimensions
      after plantar fascia release in intact and destabilized feet. Fifteen fresh
      frozen human foot specimens were used. Physiologic loads of 445 newtons were
      applied axially to simulate standing at ease, and the three-dimensional position
      of tarsal bones was determined with a magnetic tracking device. The positions
      were presented in the form of screw axis displacements, quantitating rotation,
      and axis of rotation orientation. After fasciotomy in the six intact feet,
      significant differences in rotation were observed at the talotibial and
      calcaneotalar levels. After fasciotomy in the four unstable feet with three
      supporting elements sectioned, significant differences in position were observed
      at the talotibial joint and a significant decrease in arch height was observed.
      After fasciotomy in the five unstable feet with five supporting elements
      sectioned, significant differences in rotation were observed at the talotibial
      joint (mean, 5.5 +/- 1.6 degrees; P = 0.001), calcaneotalar joint (mean, 6.1 +/-
      2.1 degrees; P = 0.003), and metatarsotalar level (mean, 9.3 +/- 4.1 degrees; P =
      0.007). The average decrease in arch height was 7.4 +/- 4.1 mm (P = 0.015).
      Displacement of all joints tested occurred after fasciotomy, with rotation about
      all three axes. These changes in displacement were more pronounced in unstable or
      destabilized feet. The data suggest that operations involving fasciotomy affect
      arch stability and should not be performed in patients with evidence of
      concomitant pes planus deformity, because of the likelihood of further
      deformation.

PMID- 9013109
TI  - Effect of partial versus complete plantar fasciotomy on the windlass mechanism.
AB  - Eight adult below-knee cadaver specimens were placed in a testing machine and
      loaded to 350 newtons according to a strict protocol. Arch height and length
      measurements were obtained in each specimen with the toes resting on the foot
      plate, dorsiflexed to 30 degrees, and maximally dorsiflexed manually. The plantar
      fascia was then divided from medial to lateral in one-quarter increments, and the
      effect on arch height and length measurements was assessed using the same loading
      protocol. A consistent decrease in the arch-supporting function on sequential
      sectioning of the plantar fascia was encountered. A less consistent decrease in
      the arch-supporting function was reflected by the increase in the height of the
      arch with sequential sectioning of the plantar fascia. The study demonstrates
      that partial plantar fasciotomy decreases the arch-supporting function of the
      plantar fascia in addition to weakening the structure. Strict surgical
      indications for this type of procedure should be maintained.

PMID- 9013110
TI  - Osteolytic changes after polyglycolide pin fixation in chevron osteotomy.
AB  - Absorbable polyglycolide pins were used for fixation of 94 chevron osteotomies in
      70 patients at the Department of Orthopaedics and Traumatology, Helsinki
      University Central Hospital, between 1986 and 1992. Postoperative osteolytic
      changes around the degrading pin occurred in 21 of 94 (22%) metatarsal heads. In
      17 of 21 metatarsal heads, polydioxanone-coated polyglycolide pins were used.
      This type of pin has not been used since 1988. At follow-up, 16 of 21 osteolytic
      changes resolved completely and four partially resolved. In the remaining one,
      the osteolytic area remained visible after 6 years. Cystic changes in the
      metatarsal head, not attributable to the location of the absorbable implants,
      occurred in seven (7.4%) metatarsal heads and avascular necrosis of the entire
      metatarsal head in one (1.1%). Foreign body reaction occurred in six (6.3%)
      metatarsal heads and wound infection in three (3.2%) metatarsal heads. No
      association was observed between osteolytic changes and foreign body reaction or
      infection. Osteolysis in patients receiving polyglycolide implants only require
      observation, because associated symptoms with the radiographic findings are
      transient.

PMID- 9013111
TI  - A comparison study of plantar foot pressure in a standardized shoe, total contact
      cast, and prefabricated pneumatic walking brace.
AB  - Total contact casting is the current recommended treatment for Wagner Stage 1 and
      2 neuropathic plantar ulcers. The rationale for this treatment includes the
      equalization of plantar foot pressures and generalized unweighting of the foot
      through a total contact fit at the calf. Total contact casting requires
      meticulous technique and multiple cast applications to avoid complications before
      ulcer healing. An alternative to total contact casting is the use of a
      prefabricated brace designed to maintain a total contact fit. This study compares
      plantar foot pressure metrics in a standardized shoe (SS), total contact cast
      (TCC), and prefabricated pneumatic walking brace (PPWB). Five plantar foot
      sensors (Interlink Electronics, Santa Barbara, CA) were placed at the first,
      third, and fifth metatarsal heads, fifth metatarsal base, and midplantar heel of
      10 healthy male subjects. Each subject walked at a constant speed over a distance
      of 280 meters in a SS, PPWB, and TCC. A custom-made portable microprocessor-based
      system, with demonstrated accuracy and reliability, was used to acquire the data.
      No significant differences in peak pressure or contact duration were found
      between the initial and repeat SS trials (P > 0.05). Peak pressures were reduced
      in the PPWB as compared to the SS for all sensor locations (P < 0.05). Similarly,
      peak pressures were reduced in the TCC compared to the SS for all sensor
      locations (P < 0.05) with the exception of the fifth metatarsal base (P = 0.45).
      Our results are summarized as follows: (1) the methods used in the current study
      were found to be reliable through a test-retest analysis; (2) the PPWB decreased
      peak plantar foot pressures to an equal or greater degree than the TCC in all
      tested locations of the forefoot, midfoot, and hindfoot; (3) compared to a SS,
      contact durations were increased in both the TCC and PPWB for most sensor
      locations; and (4) the relationship of peak pressure over time, the pressure-time
      integral, is lower in the brace compared to the shoe at the majority of sensor
      locations. The values are not significantly different between the cast and shoe.
      These findings suggest an unweighting of the plantar foot and equalization of
      plantar foot pressures with both the PPWB and TCC. Based on these findings, the
      PPWB may be useful in the treatment of neuropathic plantar ulcerations of the
      foot.

PMID- 9013112
TI  - Ultrasonographic examination of the posterior tibial tendon.
AB  - The posterior tibial tendons (PTTs) of 16 patients with PTT dysfunction and 10
      age-matched healthy subjects were examined ultrasonographically, using a 10-MHz
      linear-array transducer. Normal PTTs appeared hyperechoic (more echogenic) and
      oval, with an average diameter of 7.8 mm x 3.7 mm at the medial malleolar level.
      Degenerated PTTs appeared hypoechoic (less echogenic) and swollen (9.8 mm x 5.0
      mm). Peritendinitis presented as a hypoechoic rim on the longitudinal sonogram
      (along the long axis of the tendon) and a "target sign" (hyperechoic central
      structure with a hypoechoic halo) on the transverse sonogram (at the right angle
      to the long axis of the tendon). Complete rupture of the PTT revealed an empty
      tibial groove at the level of the medial malleolus on the transverse sonogram and
      a wavy fibril pattern over the distal end on the longitudinal sonogram. Compared
      with the operative findings or the results of the magnetic resonance imaging,
      ultrasonography was sensitive and specific in diagnosing tenosynovitis and
      complete rupture of the PTT.

PMID- 9013113
TI  - Myositis ossificans: an unusual presentation in the foot.
AB  - Myositis ossificans is a non-neoplastic lesion characterized by heterotopic
      ossification of soft tissue. At varying stages of maturity, it shares similar
      histologic characteristics with sarcomatous lesions or maturing bone.
      Misdiagnosis can result in unnecessary radical treatment. This lesion has only
      rarely been reported in the foot. We present the case of a patient with plantar
      forefoot myositis ossificans.

PMID- 9013114
TI  - Effect of the posterior tibial tendon on the arch of the foot during simulated
      weightbearing: biomechanical analysis.
AB  - A cadaver study was performed to determine the effect of the posterior tibial
      tendon (PTT) on the stability of the foot in simulated midstance phase of gait.
      Thirteen fresh-frozen human foot specimens were used. Loads were applied axially
      and to each tendon. Three-dimensional positions of tarsal bones before and after
      tendon loading were determined with the use of a magnetic tracking device.
      Significant differences in tarsal bone positions were observed with application
      of loads to the Achilles, posterior tibial, flexor digitorum longus, peroneus
      longus, and peroneus brevis tendons at the metatarsotalar, calcaneotalar, and
      talotibial joints and in overall arch height. These tendon loads caused position
      changes toward arch flattening or mild pes planus deformity. Significant
      differences in tarsal bone positions were observed with PTT loading compared with
      no PTT loading in metatarsotalar, calcaneotalar, and talotibial levels as well as
      arch height. The PTT caused position changes toward restoring the arch alignment.
      These data suggest that the PTT is an important stabilizer of the arch of the
      foot.

PMID- 9013115
TI  - Closed complete rupture of the flexor hallucis longus tendon at the groove of the
      talus.
AB  - A rare case of closed complete rupture of the flexor hallucis longus tendon at
      its groove in the posterior process of the talus is reported in a soccer player
      who developed pseudarthrosis of the posterolateral tubercle of the talus after a
      Shepherd's fracture. Partial rupture or tenosynovitis of the flexor hallucis
      longus tendon at this level is well known in classical ballet dancers and soccer
      players. Three cases of complete rupture of the flexor hallucis longus tendon
      near the metatarsophalangeal joint and three under the sustentaculum tali have
      been reported, but there have been no reports at the groove of the talus. Repair
      was accomplished by tendon graft, and active flexion of the interphalangeal joint
      is now possible.

PMID- 9013116
TI  - Nonunion of a fracture of the lateral malleolus: a case report and review of the
      literature.
AB  - Nonunion of a fracture of the lateral malleolus is a rare condition. We present a
      case of established nonunion of a fracture of the lateral malleolus confirmed and
      treated surgically, using debridement and internal fixation with autologous bone
      graft. At 5-year follow-up, the fracture was united but the patient still showed
      clinical signs of reflex sympathetic dystrophy. Male gender, supination
      fractures, Weber type C fractures, and primary internal fixation are cited as
      possible risk factors. Prognosis is variable.

PMID- 9013117
TI  - Intraosseous lipoma of the calcaneus.
AB  - We present two patients with pathologically proven intraosseous lipoma of the os
      calcis. A review of the literature, the radiologic criteria, and the differential
      diagnosis are provided.

PMID- 9013118
TI  - A further modification to the McBride procedure for hallux valgus using the
      Acufex tag system to reattach the adductor hallucis.

PMID- 9013119
TI  - The hand as a teaching tool defining the terminology of motion of the foot.

PMID- 9013120
TI  - Effects of ferulic acid on fertile and asthenozoospermic infertile human sperm
      motility, viability, lipid peroxidation, and cyclic nucleotides.
AB  - The capacity of human sperm fertilization principally depends on sperm motility
      and membrane integrity. Reactive oxygen species, such as superoxide anion and
      hydrogen peroxide, are known to impair sperm motility and membrane integrity by
      inducing membrane lipid peroxidation (LPO). Ferulic acid (FA), an effective
      constituent in various medicinal herbs, has recently been shown to scavenge
      oxygen free radicals and increase the intracellular cAMP and cGMP. The aim of
      this study is to investigate the effects of FA on human sperm motility,
      viability, lipid peroxidation, and cyclic nucleotides in fertile and
      asthenozoospermic infertile individuals in vitro. The sperm samples were obtained
      from 10 fertile volunteers and 10 asthenozoospermic infertile patients. Washed
      spermatozoa were incubated at 37 degrees C in Ham's F-10 medium with 0, 0.1, 0.2,
      0.4, 0.8, or 1.6 mM of FA. Samples were analyzed for viability, determined by
      eosin-Y dye exclusion method at 0, 1, 2, 3, 5, and 6 h of incubation; motility,
      determined by the trans-membrane migration method within 2 h of incubation; LPO,
      determined by thiobarbituric acid (TBA) method at 3 h of incubation and the
      intracellular cAMP and cGMP, determined, respectively, by 3H-cAMP and 125I-cGMP
      radioimmunoassay at 3 h of incubation. The results showed: in both fertile and
      infertile spermatozoa, the viability, trans-membrane migration ratio (TMMR) and
      the levels of intracellular cAMP and cGMP in FA-treated spermatozoa were
      significantly higher than those of spermatozoa in control groups, while TBA
      reactive substances contents in treated spermatozoa were significantly lower than
      those in control spermatozoa. The effects of FA on these processes were
      concentration dependent. These data suggested that FA is beneficial to sperm
      viability and motility in both fertile and infertile individuals, and that
      reduction of lipid peroxidative damage to sperm membranes and increase of
      intracellular cAMP and cGMP may be involved in these benefits. It is possible
      that FA may be used for cure of asthenozoospermic infertility.

PMID- 9013121
TI  - Abnormalities of retinal metabolism in diabetes or experimental galactosemia. IV.
      Antioxidant defense system.
AB  - Activities of enzymes that protect the retina from reactive oxygen species were
      investigated in experimentally diabetic rats and experimentally galactosemic
      rats, two animal models known to develop vascular lesions consistent with
      diabetic retinopathy. Diabetes or experimental galactosemia of 2 months duration
      significantly decreased the activities of glutathione reductase and glutathione
      peroxidase in the retina while having no effect on the glutathione synthesizing
      enzymes glutathione synthetase and gamma-glutamyl cysteine synthetase. Activities
      of two other important antioxidant defense enzymes-superoxide dismutase (SOD) and
      catalase-also were decreased (by more than 25%) in retinas of diabetic rats and
      galactosemic rats. Administration of supplemental antioxidants, vitamins C and E,
      for the 2 months prevented the diabetes-induced impairment of antioxidant defense
      system in the retina. In experimentally galactosemic rats, the supplemental
      antioxidants were not as effective: SOD activity was normalized, but the enzymes
      of the glutathione redox cycle were only partly restored, and the subnormal
      catalase activity was unaffected. Diabetes or experimental galactosemia results
      in significant impairment of the antioxidant defense system in the retina, and
      exogenous antioxidant supplementation can help alleviate the subnormal activities
      of antioxidant defense enzymes.

PMID- 9013122
TI  - The effect of oxygen radicals metabolites and vitamin E on glycosylation of
      proteins.
AB  - Glycosylation (glycation) of proteins is a major complication of hyperglycemia in
      diabetes. This study has examined the effect of hydrogen peroxide (H2O2) and
      tertiary-butylhydroperoxide (TBH) and vitamin E (E) on glycation of hemoglobin
      (GHb). The RBC (15%) in phosphate-buffered saline were treated with 5-50 mM
      glucose (G) with and without H2O2 or TBH at 37 degrees C for 1-3 d. Glycation of
      hemoglobin was assessed by GHb formation using Glyc-affinity columns. There was
      an increase in the GHb formation with increasing G concentrations. GHb formation
      increased significantly in the presence of H2O2 at all G concentrations. The
      increase in GHb was blocked when RBC were pretreated with E. E also inhibited
      formation of malondialdehyde (MDA), an end product of lipid peroxidation, as
      assessed by the thiobarbituric acid reactivity. Similar increase in the GHb
      formation was observed when TBH was used instead of H2O2 to induce oxidant stress
      to the RBC. To examine any role of MDA per se in increased glycation, RBC were
      treated ex vivo with and without exogenous standard MDA. GHb formation was
      significantly higher with G-MDA in contrast to G alone. Thus, increased oxygen
      radicals activity can initiate per-oxidation of lipids and MDA accumulation,
      which in turn, can stimulate glycation of proteins in diabetes. E can block the
      glycation of proteins by inhibiting MDA formation.

PMID- 9013123
TI  - An adenosine deaminase inhibitor prevents puromycin aminonucleoside
      nephrotoxicity.
AB  - Puromycin aminonucleoside (PAN) toxicity was totally inhibited in the rat in vivo
      and in cultured glomerular epithelial cells (GECs) in vitro using the adenosine
      deaminase (ADA) inhibitor, 2'-deoxycoformycin (DCF). DCF completely inhibited ADA
      activity in glomeruli and protected against the development of PAN nephrosis; the
      24-h urinary protein excretion of treated rats compared with controls (PAN rats)
      9 days after PAN injection was 16 +/- 2 mg and 524 +/- 55 mg, respectively (p <
      .01). Morphological examination also demonstrated that the glomerular epithelial
      cells were protected against PAN-induced damage. Furthermore, when DCF was added
      to the first passage of GECs simultaneously with PAN, the adenosine triphosphate
      contents of remnant GECs on culture substrata increased in a dose-dependent
      manner, and PA toxicity was completely inhibited by 10(-4) M DCF. The order of
      ADA activity in glomeruli from various species was as follows: rat > monkey >
      guinea pig > dog > rabbit > mouse. High activity of ADA in the glomerulus was
      limited to species in which PAN induced nephrosis. Additionally, DCF increased
      glomerular cyclic AMP contents, resulting from enhanced adenosine accumulation in
      the pericellular space. These results indicate that the pathogenesis of PAN
      toxicity is closely related to adenosine metabolism and that ADA plays a key role
      in this model. Furthermore, we speculate that DCF contributes to the inhibition
      of reactive oxygen metabolites by decreasing the substrate of xanthine oxidase
      and/or increasing pericellular adenosine accumulation.

PMID- 9013124
TI  - Evidence for embryonic prostaglandin H synthase-catalyzed bioactivation and
      reactive oxygen species-mediated oxidation of cellular macromolecules in
      phenytoin and benzo[a]pyrene teratogenesis.
AB  - A mouse embryo culture model was used to determine whether embryonic
      prostaglandin H synthase (PHS)-catalyzed bioactivation and resultant oxidative
      damage to embryonic protein and DNA may constitute a molecular mechanism
      mediating phenytoin and benzo[a]pyrene teratogenesis. Embryos were explanted from
      CD-1 mouse dams on gestational day 9.5 (vaginal plug = day 1) and incubated for
      either 4 h (biochemistry) or 24 h (embryotoxicity) at 37 degrees C in medium
      containing either phenytoin (20 micrograms/ml, 80 microM), benzo[a]pyrene (10
      microM), or their respective vehicles. As previously observed with phenytoin
      (Mol. Pharmacol.48: 112-120, 1995), embryos incubated with benzo[a]pyrene showed
      decreases in anterior neuropore closure, turning, yolk sac diameter, and somite
      development (p < .05). Addition of the antioxidative enzyme superoxide dismutase
      (SOD) substantially enhanced embryonic SOD activity (p < .05) and completely
      inhibited benzo[a]pyrene embryotoxicity (p < .05). Substantial PHS was detected
      in day 9.5 embryos using SDS/PAGE, anti-PHS antibody, and alkaline phosphatase
      conjugated donkey anti-goat IgG. Embryonic protein oxidation was detected by the
      reaction of 0.5 mM 2,4-dinitrophenylhydrazine with protein carbonyl groups. This
      method was first validated by using a known hydroxyl radical-generating system
      consisting of vanadyl sulfate and H2O2, with bovine serum albumin or embryonic
      protein as the target. Embryonic proteins were characterized by SDS/PAGE, anti
      dinitrophenyl antisera, and peroxidase-labeled goat anti-donkey IgG. Using
      enhanced chemiluminescence, the number and content of oxidized protein bands
      detected between 25 and 200 kDa were substantially increased by both phenytoin
      and benzo[a]pyrene. Addition of the reducing agent dithiothreitol, or SOD or
      catalase, decreased protein oxidation in phenytoin-exposed embryos. Both
      phenytoin (Mol. Pharmacol.48: 112-120, 1995) and benzo[a]pyrene enhanced
      embryonic DNA oxidation, determined by the formation of 8-hydroxy-2'
      deoxyguanosine, as measured by high-performance liquid chromatography (HPLC) (p <
      .05). Phenytoin also enhanced the oxidation of embryonic glutathione (GSH) to its
      GSSG disulfide, as measured by HPLC (p < .05). These results provide direct
      evidence that, in the absence of maternal or placental processes, embryonic PHS
      catalyzed bioactivation and reactive oxygen species-mediated oxidation of
      embryonic protein, thiols, and DNA may constitute a molecular mechanism mediating
      phenytoin and benzo[a]pyrene teratogenesis.

PMID- 9013125
TI  - Oxidative modulation of cyclic AMP-dependent protein kinase in human fibroblasts:
      possible role in psoriasis.
AB  - Previous studies have established that cyclic AMP-dependent protein kinase (PKA)
      activity, as well as 8-azido-[32P]-cAMP binding to the RI and RII regulatory
      subunits, are decreased in cells from psoriatic patients compared to cells from
      normal patients. Here we show that the exposure of normal human dermal
      fibroblasts in culture to hydrogen peroxide and to oxygen free-radical generating
      systems decreased PKA activity, as well as cyclic AMP binding to the RI and RII
      regulatory subunits, to levels similar to those observed with psoriatic
      fibroblasts. Likewise, treatment of normal cytosolic preparations of PKA, as well
      as purified bovine PKA II, in vitro with free radical generating systems also
      resulted in decreased PKA activity and 8-azido [32P]-cAMP binding to the RI and
      RII regulatory subunits. Further, treatment of psoriatic fibroblasts with free
      radical scavenging agents such as vitamins E and C, and mannitol, and also with
      superoxide dismutase, restored the ability of RI and RII to bind 8-azido-[32P]
      cAMP toward normal levels. Western blot analysis showed that the protein levels
      of the RI and RII subunits are similar in normal and psoriatic fibroblasts, and
      that the amounts of RI and RII are not altered by treatment of the cells with
      free radical-generating systems. These results suggest that oxidative
      modification may serve as a mechanism to alter PKA activity in human cells, and
      that an altered oxidative state may be involved in mediating the decrease in PKA
      activity and cyclic AMP binding noted in cells from psoriatic patients.

PMID- 9013126
TI  - Role of ascorbate and protein thiols in the release of nitric oxide from S
      nitroso-albumin and S-nitroso-glutathione in human plasma.
AB  - In this work we investigated the stability in aerobic plasma of two naturally
      occurring S-nitrosothiols, the S-nitroso adduct of serum albumin (S-NO-albumin)
      and the S-nitroso adduct of glutathione (S-NO-glutathione). In contrast to their
      behavior in physiological buffers, in which they are stable, in plasma these S
      nitrosothiols showed a slow but continuous release of .NO. In the presence of red
      blood cells, the .NO was quantitatively oxidized to NO3- with stoichiometric
      formation of methemoglobin. In the absence of red blood cells, the principal
      oxidation product was NO2- with small amounts of NO3- (about 1/5 of the amount of
      NO2-). The release of .NO was also proven by spin trapping experiments with 2-(4
      Carboxyphenyl)4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide which, when added to
      plasma in the presence of S-NO-glutathione, was transformed into 2-(4
      carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl. Both dialysable and
      nondialysable compounds are involved in the release of .NO from S-nitrosothiols.
      Ascorbate and the thiol group of serum albumin are the plasma components mainly
      involved in the release of .NO, while endogenous L-cysteine and glutathione play
      a minor role due to their relative low concentrations. However, in contrast to
      the thiol-dependent release that is known to induce the formation of disulfides,
      the ascorbate-dependent release of .NO from S-NO-glutathione resulted in the
      formation of free sulfhydryls. Our results suggest that in plasma the .NO release
      from S-NO-albumin and S-NO-glutathione may be regulated by heterolytic NO+
      transfer and reductive activation to .NO, rather than by homolytic decomposition
      of labile S-nitrosothiols.

PMID- 9013127
TI  - Regulation of protein-tyrosine phosphorylation and human sperm capacitation by
      reactive oxygen derivatives.
AB  - Spermatozoa undergoing capacitation, a necessary prerequisite event to successful
      fertilization that can be induced in vitro by reactive oxygen species (ROS),
      generate superoxide anion (O2.-). Because, in neutrophils, the generation of O2.-
      is associated with tyrosine phosphorylation of several proteins, the aim of the
      present study was to investigate the association between protein-tyrosine
      phosphorylation and ROS-induced human sperm capacitation. Human spermatozoa
      express two major phosphotyrosine-containing proteins of 105 and 81 kDa, the
      phosphotyrosine content of which is increased when spermatozoa are incubated
      under capacitating conditions. Superoxide dismutase and catalase abolish both
      sperm capacitation and tyrosine phosphorylation of p105 and p81, suggesting the
      involvement of O2.- and hydrogen peroxide in these two processes. Inhibitors of
      NADPH oxidase, the enzyme responsible for the neutrophil's respiratory burst,
      decrease both p105 and p81 tyrosine phosphorylation and sperm capacitation while
      hydrogen peroxide stimulates these two processes. Tyrosine phosphorylation of
      p105 and p81 occurs through a herbimycin A-sensitive tyrosine kinase, and sperm
      incubation with phosphotyrosine-protein phosphatase inhibitors results in an
      increase in phosphotyrosine content of these two proteins. Indirect
      immunocytochemical studies reveal phosphotyrosine-containing proteins mostly in
      the principal piece of the flagellum, in agreement with the localization of p105
      and p81 in the human sperm fibrous sheath. Although tyrosine phosphorylation of
      p105 and p81 and sperm capacitation are related in a time-dependent fashion, some
      discrepancies are observed in the regulation of these two processes according to
      the redox status of the spermatozoa.

PMID- 9013128
TI  - On the molecular mechanism of metmyoglobin-catalyzed reduction of hydrogen
      peroxide by ascorbate.
AB  - Hydrogen peroxide induces rapid oxidation of metmyoglobin with an apparent second
      order rate constant, k1 = 3.4 x 10(4) M-1 min-1. The product of this interaction
      is ferrylmyoglobin with an unstable free radical on the globin moiety. This
      activated form of myoglobin is able: (a) to initiate the peroxidation of
      erythrocyte membranes and (b) to form intra- and intermolecular covalent
      crosslinkings. The presence of ascorbic acid in amounts stoichiometric to H2O2
      efficiently prevents all the above processes. Moreover, in the presence of
      ascorbic acid a cyclic process is taking place leading to H2O2 reduction,
      ascorbic acid oxidation, and unmodified metmyoglobin formation (reaction 1).

PMID- 9013129
TI  - Quercetin protects cutaneous tissue-associated cell types including sensory
      neurons from oxidative stress induced by glutathione depletion: cooperative
      effects of ascorbic acid.
AB  - Oxidation reactions are essential biological reactions necessary for the
      formation of high-energy compounds used to fuel metabolic processes, but can be
      injurious to cells when produced in excess. Cutaneous tissue is especially
      susceptible to damage mediated by reactive oxygen species and low-density
      lipoprotein oxidation, triggered by dysmetabolic diseases, inflammation,
      environmental factors, or aging. Here we have examined the ability of the
      flavonoid quercetin to protect cutaneous tissue-associated cell types from injury
      induced by oxidative stress, and possible cooperative effects of ascorbic acid.
      Human skin fibroblasts, keratinocytes, and endothelial cells were cultured in the
      presence of buthionine sulfoximine (BSO), an irreversible inhibitor of
      glutathione (GSH) synthesis. Depletion of intracellular levels of GSH leads to an
      accumulation of cellular peroxides and eventual cell death. Quercetin
      concentration-dependently (EC50: 30-40 microM) reduced oxidative injury of BSO to
      all cell types, and was also effective when first added after BSO washout. BSO
      caused marked decreases in the intracellular level of GSH, which remained
      depressed in quercetin-protected cells. Ascorbic acid, while by itself not
      cytoprotective synergized with quercetin, lowered the quercetin EC50 and
      prolonged the window for cytoprotection. The related flavonoids rutin and
      dihydroquercetin also decreased BSO-induced injury to dermal fibroblasts, albeit
      less efficaciously so than quercetin. The cytoprotective effect of rutin, but not
      that of dihydroquercetin, was enhanced in the presence of ascorbic acid. Further,
      quercetin rescued sensory ganglion neurons from death provoked by GSH depletion.
      Direct oxidative injury to this last cell type has not been previously
      demonstrated. The results show that flavonoids are broadly protective for
      cutaneous tissue-type cell populations subjected to a chronic intracellular form
      of oxidative stress. Quercetin in particular, paired with ascorbic acid, may be
      of therapeutic benefit in protecting neurovasculature structures in skin from
      oxidative damage.

PMID- 9013130
TI  - Possible involvement of free radical scavenging properties in the action of tumor
      necrosis factor-alpha.
AB  - Constitutive production of hydroxyl radicals from four established cancer cell
      lines was detected as spin adducts of 5,5-dimethyl-l-pyroline-N-oxide (DMPO),
      using an electron spin resonance spectrometer. The generated hydroxyl radicals
      was decreased in three out of four cancer cell lines when incubated in vitro for
      3 h with TNF-alpha No direct scavenging effect of TNF-alpha on hydroxyl radicals
      or superoxide anions was observed in the in vitro radical generation system. The
      modulation of intracellular reactive oxygen species of these cancer cells by
      adding menadione or CuDIPS to the culture medium changed the antiproliferative
      effect of TNF-alpha on the cells. The ultrastructural localization of the radical
      generating sites in cancer cells was visualized using the
      diaminobenzidine/horseradish peroxide histochemical system at the electron
      microscopic level. The hydrogen peroxide-dependent formation of electron-dense
      materials localized at the mitochondrial membranes was decreased after the
      treatment of the cancer cells with TNF-alpha. These data indicate that the
      reduction of radical generation in cancer cells by TNF-alpha may be an early
      mechanism that contributes to the antiproliferative effect of this cytokine on
      some cancer cells.

PMID- 9013131
TI  - Autoxidation of naphthohydroquinones: effects of metals, chelating agents, and
      superoxide dismutase.
AB  - At neutral pH, 1,4-naphthohydroquinone and 2-methyl-1,4-naphthohydroquinone
      readily autoxidize to the corresponding quinones. In an unpurified phosphate
      buffer, the autoxidation of both substances proceeded in a linear fashion after a
      brief lag phase. Addition of a chelating agent or purification of the buffer
      decreased the duration of the lag phase of 1,4-naphthohydroquinone autoxidation,
      but had no effect on the linear rate. In the case of 2-methyl-l,4
      naphthohydroquinone, such treatment eliminated the lag phase and greatly
      increased the linear rate of oxidation. The lag phases and oxidation rates seen
      in unpurified buffers could be replicated by addition of submicromolar amounts of
      copper to purified buffer. The effects of low levels of copper were qualitatively
      similar to those of superoxide dismutase, and it is suggested that the effects of
      this metal on naphthohydroquinone autoxidation reflects its ability to act as a
      superoxide dismutase. The relative rates of autoxidation of naphthohydroquinones
      are important because they may determine the balance between activation and
      detoxication of naphthoquinones within cells. When measuring such rates, or
      assessing rates of redox cycling of naphthoquinones, it is important to employ a
      chelating agent or use highly purified buffers and reagents. Failure to do so may
      lead to erroneous conclusions concerning the reactivity of naphthohydroquinones
      and the ability of naphthoquinones to generate "active oxygen" species.

PMID- 9013132
TI  - Antioxidant defense system in differentially hydrogen peroxide sensitive L5178Y
      sublines.
AB  - Two sublines of L5178Y (LY) murine lymphoma, differing in sensitivity to hydrogen
      peroxide, served as a cellular model for examination of the antioxidant defense
      system. The contribution of catalase, glutathione peroxidase (G-Px) and
      glutathione were evaluated. Sensitivity to 3-amino-1,2,4-triazole (AMT),
      inhibitor of catalase, was higher in LY-R (hydrogen peroxide sensitive) than in
      LY-S (hydrogen peroxide resistant) cells. Accordingly, activity of catalase was
      twofold lower in LY-R than in LY-S cells. G-Px activity was about two times
      higher in LY-R than in LY-S cells. After induction with selenium it increased
      15.6 times in LY-R cells and 50.3 times in LY-S cells. Reduced glutathione (GSH)
      content (and possibly other monobromobimane-reactive thiols) were determined
      fluorimetrically with monobromobimane and fluorescence found 54% higher in LY-S
      than in LY-R cells. Inhibition of catalase caused GSH decrease in LY-S cells;
      this decrease was abrogated by inducing G-Px by selenium treatment. On the
      contrary, in LY-R cells inhibition of catalase decreased GSH content only
      slightly and selenium treatment did not further change the GSH level. DNA damage
      (estimated by "comet" assay) was the same in hydrogen peroxide-treated cells in
      the presence or absence of AMT; however, after induction of G-Px by selenium, DNA
      damage was considerably lowered. This sparing effect of selenium was accompanied
      by decreased growth inhibition in selenium pretreated, hydrogen peroxide-treated
      cell cultures.

PMID- 9013134
TI  - Role of rebamipide on induction of heat-shock proteins and protection against
      reactive oxygen metabolite-mediated cell damage in cultured gastric mucosal
      cells.
AB  - Reactive oxygen metabolites (ROM) have been reported to be important in the
      pathogenesis of ischemia/ reperfusion-, ethanol-, nonsteroidal antiinflammatory
      drug-, or Helicobacter pylori-induced gastric mucosal injury. Rebamipide, a novel
      antiulcer agent, has been reported either to prevent various acute experimental
      gastric mucosal lesions or to accelerate the healing of chronic gastric ulcers.
      The underlying mechanism by which rebamipide exerts its cytoprotective effect in
      the damaged stomach is not fully determined. We investigated the role of
      rebamipide in protecting against ROM-mediated cell damage in gastric mucosal
      cells and in inducing cytoprotective proteins. Cells were exposed to ROM
      enzymatically generated by hypoxanthine-xanthine oxidase. Cytotoxicity was
      quantified by measuring specific 51Cr release from prelabeled cells. ROM caused
      dose-dependent increase in cytotoxicity and amount of thiobarbituric acid
      reactive substances (TBA-RS). ROM-induced cytotoxicity and TBA-RS were dose
      dependently decreased by the addition of rebamipide and/or catalase, but not by
      superoxide dismutase alone. The effects of rebamipide on electric spin resonance
      signal were investigated. We found that the DMPO spin adduct ESR signal of
      hydroxyl radicals (DMPO-OH) was significantly attenuated by rebamipide. Western
      blot analysis showed that induction of heat-shock protein (HSP70) was
      significantly increased following rebamipide administration in a dose-dependent
      manner. Based on these results, it is concluded that rebamipide exerted a
      protective effect on HX-XO-induced gastric mucosal cell cytotoxicity through one
      or more of the following mechanism(s): (1) inhibition of lipid peroxidation of
      the cell membrane; (2) hydroxyl radical scavenging activity; and (3) induction of
      cellular cytoprotective protein such as HSP70.

PMID- 9013133
TI  - A modified form of low-density lipoprotein with increased electronegative charge
      is present in rheumatoid arthritis synovial fluid.
AB  - Reactive oxygen species (ROS) are pro-inflammatory factors in the pathogenesis of
      rheumatoid arthritis. During inflammation, the amount of low-density lipoprotein
      (LDL) in the inflamed joint is increased. LDL is known to be susceptible to
      oxidation by ROS. Oxidized LDL may serve as a mediator for joint damage, further
      exacerbating the inflammatory process. LDL isolated from synovial fluid and
      plasma from individual patients (paired samples) with rheumatoid arthritis or
      osteoarthritis was characterized by crossed immunoelectrophoresis. On analysis by
      this technique, synovial fluid LDL from most patients with rheumatoid arthritis
      contained two peaks: one corresponding to normal plasma native LDL, and the other
      having an increased electrophoretic mobility associated with oxidized LDL. Paired
      plasma LDL samples contained native LDL alone, as did paired synovial fluid and
      plasma LDL from patients with osteoarthritis. Thus, in addition to native LDL, a
      second form of LDL was shown to be present in rheumatoid synovial fluid, which
      had properties consistent with those of oxidized LDL.

PMID- 9013135
TI  - The influence of cell growth, detoxifying enzymes and DNA repair on hydrogen
      peroxide-mediated DNA damage (measured using the comet assay) in human cells.
AB  - Single-cell gel electrophoresis (the comet assay) is a sensitive method for
      detecting strand breaks at the level of individual cells. Cells embedded in
      agarose are lysed, electrophoresed, and fluorescently stained. Breaks in the DNA
      release its supercoiling and allow DNA to extend toward the anode, resembling a
      comet. We have used the comet assay to investigate the influence of growth state,
      xenobiotic detoxifying enzymes, and DNA repair processes on the response of
      cultured human cells to oxidative damage. HepG2 and Caco-2 cells are
      differentiated liver and colon cell lines, respectively. HeLa and GM1899A cells
      are relatively unspecialized epithelial and lymphoblastoid cells. Substrate
      dependent cells showed a cyclical fluctuation of glutathione (GSH) with respect
      to growth. Enzyme activities (glutathione reductase, glutathione peroxidase, and
      catalase) varied considerably between cell types and changed with cell growth
      state. Hydrogen peroxide induced more DNA damage in actively dividing cells than
      in confluent cultures. Sensitivity to oxidative injury did not correlate with
      detoxifying enzyme activity. Rather, differences in susceptibility between cells
      could be correlated with differences in DNA repair capacity. This study
      highlights the need to standardize experimental conditions if the comet assay is
      to be employed in the study of genotoxicity.

PMID- 9013136
TI  - Production of hydroxyl radical in the hippocampus after CO hypoxia or hypoxic
      hypoxia in the rat.
AB  - Carbon monoxide poisoning produces both immediate and delayed neuronal injury in
      selective regions of the brain that is not readily explained on the basis of
      tissue hypoxia. One possibility is that cellular injury during and after CO
      poisoning is related to the production of reactive oxygen species (ROS) by the
      brain. In this study, we hypothesized that the extent of ROS generation in the
      brain would be greater after CO than after hypoxic hypoxia due to intracellular
      uptake of CO. We assessed hydroxyl radical (OH.) production by comparing the
      nonenzymatic hydroxylation of salicylic acid to 2,3-dihydroxybenzoic acid (2,3
      DHBA) in the hippocampus of the rat by microdialysis during either CO hypoxia or
      an exposure to hypoxic hypoxia that produced similar PO2 and cerebral blood flow
      (CBF) values in the region of microdialysis. We found neither control animals nor
      animals exposed to 30 min of hypoxic hypoxia at a mean tissue PO2 of 15 mmHg
      demonstrated significant increases in 2,3-DHBA production in the hippocampus over
      the 2-h the exposure. In contrast, CO exposed rats which also developed brain PO2
      values in the range of 15 mmHg showed highly significant increases in 2,3-DHBA
      production. We conclude that cerebral oxidative stress in the hippocampus of the
      rat during CO hypoxia in vivo is not a direct effect of decreased tissue oxygen
      concentration.

PMID- 9013137
TI  - Hydroxyl and peroxyl radical trapping by the monoamine oxidase-B inhibitors
      deprenyl and MDL 72,974A: implications for protection of biological substrates.
AB  - We have examined in vitro radical trapping by the monoamine oxidase-B (MAO-B)
      inhibitor deprenyl and compared it to the specific MAO-B inhibitor MDL 72,974A.
      The capacity for the compounds to prevent .OH-mediated oxidation of biological
      substrates was examined by determining their ability to inhibit oxidation of 2
      deoxyribose and phosphatidylcholine liposomes using the thiobarbituric acid
      reactive substances (TBARS) assay. MDL 72,974A gave a dose-dependent inhibition
      of 2-deoxyribose oxidation, while deprenyl generated a strong false positive
      TBARS reaction with both the sugar and the liposomes. When lipid peroxidation was
      monitored by conjugated diene formation, deprenyl inhibited oxidation while MDL
      72,974A was without effect suggesting that trapping of .OH was not responsible
      for activity. Deprenyl inhibited liposomal peroxidation initiated with the water
      soluble peroxyl radical generator 2,2'-azobis (2-amidinopropane) (ABAP) with an
      IC50 of 78 microM as compared to 4.2 mM for MDL 72,974A. A similar difference was
      observed using the lipophilic peroxyl radical generator 2,2'-azobis (2,4
      dimethylvaleronitrile) (AMVN). The data indicate that radical trapping by the MAO
      B inhibitors provides differential protection against biological substrates and
      may involve trapping of secondary peroxyl radicals rather than .OH.

PMID- 9013138
TI  - Moderate zinc deficiency in rats enhances lipoprotein oxidation in vitro.
AB  - Zinc inhibits low density lipoprotein oxidation in vitro. This observation and
      others provide indirect evidence that Zn affects radical-mediated processes. This
      study demonstrated that moderate Zn deficiency in rats produced very low and low
      density lipoproteins with abnormally high sensitivity to copper-catalyzed
      oxidation in vitro (short lag time, high propagation rate). The amount of Zn in
      the oxidation assay did not appear to contribute to the results. Because
      lipoprotein oxidation in vitro seems to reflect certain oxidative processes in
      vivo, this study strengthened the contention that Zn affects radical-mediated
      damage in vivo.

PMID- 9013162
TI  - Sedation and analgesia for colonoscopy: patient tolerance, pain, and
      cardiorespiratory parameters.
AB  - BACKGROUND: Colonoscopy is generally performed with the patient sedated and
      receiving analgesics. However, the benefit of the most often used combination of
      intravenous midazolam and pethidine on patient tolerance and pain and its
      cardiorespiratory risk have not been fully defined. METHODS: In this double-blind
      prospective study, 150 outpatients undergoing routine colonoscopy were randomly
      assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and
      pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients),
      (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam.
      RESULTS: Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 =
      unbearable) did not improve significantly more in group 1 compared with group 2
      (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence
      interval [-7-12]). Similarly, pain was not significantly improved in group 1 as
      compared with the other groups. Male gender (p < 0.001) and shorter duration of
      the procedure (p = 0.004), but not amnesia, were associated with better patient
      tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen
      desaturation and hypotension occurred in 33% and 11%, respectively, with a
      similar frequency in all three groups. CONCLUSIONS: In this study, the
      combination of low-dose midazolam and pethidine does not improve patient
      tolerance and lessen pain during colonoscopy as compared with either drug given
      alone. When applying low-dose midazolam, oxygen desaturation and hypotension do
      not occur more often after combined use of both drugs. For the individual
      patient, sedation and analgesia should be based on the endoscopist's clinical
      judgement.

PMID- 9013163
TI  - Nitrous oxide inhalation as sedation for flexible sigmoidoscopy.
AB  - BACKGROUND: Flexible sigmoidoscopy is usually performed without sedation in
      screening programs for colorectal cancer. Most patients report some degree of
      discomfort or pain during the procedure. The aim of this study was to evaluate
      self-administered nitrous oxide as a method to reduce patient discomfort, thereby
      improving the procedure and conceivably increasing patient compliance and
      motivation. METHODS: In a double-blind, randomized, placebo-controlled study, 38
      patients undergoing sigmoidoscopy self-administered 60% nitrous oxide (n = 18) or
      oxygen (n = 20) by mask. The endoscopist recorded the depth of insertion of the
      sigmoidoscope, duration of the procedure, and time to patient recovery. Patients
      scored the degree of pain and discomfort felt during the examination. RESULTS:
      There were no significant differences between the groups with regard to patients'
      age, gender, pain or discomfort, duration of procedure, or depth of insertion.
      Recovery time was significantly longer in the nitrous oxide group (3.3 +/- 0.6
      minutes vs 0.5 +/- 0.5 minutes; p = 0.02), but this finding was of no practical
      or clinical consequence. CONCLUSIONS: The addition of "on demand" nitrous oxide
      did not improve sigmoidoscopy performance or diminish pain and discomfort.
      However, further studies using improved administration techniques and larger
      study groups are justified in the search for ways to increase compliance with and
      motivation for colorectal cancer screening.

PMID- 9013164
TI  - Overuse of upper gastrointestinal endoscopy in a country with open-access
      endoscopy: a prospective study in primary care.
AB  - BACKGROUND: This prospective observational study was aimed at evaluating the
      appropriateness of use of upper gastrointestinal endoscopy (UGE) in primary care
      in a country with open access to and high availability of the procedure. METHODS:
      Outpatients were consecutively included in two clinical settings: Setting A (20
      primary care physicians during 4 weeks) and B (university-based outpatient clinic
      during 3 weeks). In patients undergoing UGE, appropriateness of referral was
      judged by explicit Swiss criteria developed by the RAND/UCLA panel method.
      RESULTS: Patient visits (8135) were assessed. Six hundred eleven patients
      complained of upper gastrointestinal symptoms. Physicians decided to perform UGE
      in 63 of these patients. Twenty-five (40%) of the endoscopies were rated
      appropriate, 7 (11%) equivocal, and 31 (49%) inappropriate. Overuse of UGE
      occurred in 5.1% (setting A: 4.7%; setting B:6.5%; p = 0.39) of the patients who
      presented with upper gastrointestinal symptoms. The decision to perform UGE in
      previously untreated dyspeptic patients was the most common clinical situation
      resulting in overuse. CONCLUSIONS: Inappropriate use of UGE is high in
      Switzerland. However, to better reflect primary care decision making, overuse
      should be related not only to patients referred for a medical test, but also to
      the number of patients who complain of the symptoms that would be investigated by
      the procedure.

PMID- 9013165
TI  - A randomized prospective study of endoscopic bipolar electrocoagulation and
      heater probe treatment of chronic rectal bleeding from radiation telangiectasia.
AB  - BACKGROUND: Our purposes were to (1) evaluate efficacy and safety of bipolar or
      heater probe endoscopic coagulation compared to prior medical therapy for
      bleeding radiation telangiectasia, and (2) consider the impact of treatments on
      patients' impression of their overall health and activity. METHODS: Twelve months
      of medical management had failed in 18 men and 3 women with chronic, recurrent
      hematochezia and anemia after radiation treatment of pelvic malignancies.
      Patients had multiple rectal telangiectasias coagulated with bipolar or heater
      probes in a randomized, prospective study. RESULTS: Rectal bleeding stopped
      within four treatment sessions. During 12 months of endoscopic versus medical
      therapy, severe bleeding episodes diminished significantly for bipolar probe
      versus 12 months of prior medical therapy (75% vs 33%) and heater probe (67% vs
      11%); mean hematocrits rose significantly for patients undergoing bipolar (38.2
      vs 31.9) and heater probe (37.6 vs 28.4) treatments, and their impression of
      overall health improved. During long-term follow-up, new telangiectasias or
      rectal bleeding were easily controlled. No major complications resulted.
      CONCLUSIONS: (1) Bipolar or heater probes were safe and effective relative to
      medical therapy for palliation of patients with lower gastrointestinal bleeding
      from radiation telangiectasias, and (2) all patients improved in ability to
      travel and exercise and in their overall impression of their health.

PMID- 9013166
TI  - A retrospective and prospective study on the safety of discharging selected
      patients with duodenal ulcer bleeding on the same day as endoscopy.
AB  - BACKGROUND: Low risk of rebleeding has been observed in patients with
      gastrointestinal bleeding due to peptic ulcer without high-risk stigmata of
      recent hemorrhage. We aimed to evaluate the safety and acceptability of an
      aggressive early discharge policy in those patients admitted with upper
      gastrointestinal bleeding due to duodenal ulcers without high-risk stigmata of
      recent hemorrhage. METHOD: Retrospective analysis was carried out in bleeding
      ulcer patients less than 60 years of age with stable vital signs and no stigmata
      or only flat spots on endoscopy. A prospective study was then performed that
      included only duodenal ulcer patients less than 60 years of age with stable vital
      signs, no concomitant serious medical illness, and no stigmata of recent
      hemorrhage. These patients were discharged on the same day that endoscopy was
      performed. RESULTS: During a period of 18 months, 72 patients satisfied the
      criteria in the retrospective study. The mean hospital stay was 1.4 days (range,
      1 to 5). There were no episodes of rebleeding nor significant drops in hemoglobin
      level 2 weeks after discharge (10.8 gm/dL +/- 1.4 vs 11.0 gm/dL +/- 1.5). Seventy
      five patients were recruited into the prospective study. None of them had
      rebleeding nor significant drops in hemoglobin 1 week after discharge (12.1 gm/dL
      +/- 1.8 vs 11.7 gm/dL +/- 2.5). CONCLUSION: We conclude that patients with
      gastrointestinal bleeding who have clean-based duodenal ulcers and are stable on
      admission can be safely discharged on the same day as endoscopy.

PMID- 9013167
TI  - Silicone-covered Wallstent prototypes for palliation of malignant esophageal
      obstruction and digestive-respiratory fistulas.
AB  - BACKGROUND: Endoscopic palliation of malignant esophageal obstruction with
      uncovered self-expanding metal stents has been shown to have fewer complications
      than with conventional plastic stents. The addition of a membrane might prevent
      tumor ingrowth and allow treatment of digestive-respiratory fistulas. We report
      the clinical experience with a prototype silicone membrane-covered self-expanding
      metal stent. METHODS: Twenty-three silicone membrane-covered Wallstent prototypes
      were used in 21 patients with dysphagia due to inoperable malignant tumors
      involving the esophagus and cardia. RESULTS: Stent implantation was technically
      successful in all patients. There were no procedure-related perforations or
      deaths. The prototype stent was successful in sealing seven of the eight (87.5%)
      digestive-respiratory fistulas. As a group, the mean dysphagia grade improved
      significantly after stent placement (4.8 +/- 0.9 vs 3.4 +/- 1.6, p < 0.0005).
      However, 9 of 21 (42.9%) patients experienced no improvement in their dysphagia.
      Complications occurred in 13 of 21 (61.9%) patients. Tumor ingrowth was not
      observed in any patient. CONCLUSIONS: The prototype covered self-expanding metal
      stent was effective in sealing digestive-respiratory fistulas and provided
      palliation of dysphagia in slightly more than one half of the patients studied. A
      great deal has been learned from the preliminary experience, which has led to
      design modifications. The utility of the commercially available device should be
      evaluated in further prospective clinical trials.

PMID- 9013168
TI  - Chronic esophagitis dissecans: an unrecognized clinicopathologic entity?
AB  - BACKGROUND: We report the clinical and histologic features of a distinctive form
      of chronic esophagitis for which we propose the term chronic esophagitis
      dissecans. METHODS: The study group included five patients diagnosed at Hopital
      Beaujon, Clichy, from 1988 to 1994. Clinical and endoscopic examinations were
      performed. Samples of esophageal biopsy specimens were analyzed by histologic and
      ultrastructural examinations and by immunohistochemistry with antibodies directed
      against cell adhesion molecules. RESULTS: All patients were elderly (mean age, 66
      years). They presented the following combination of clinical and endoscopic
      features: (1) long-standing history of chronic dysphagia, without symptoms of
      reflux, (2) shedding of mucosal fragments, occurring spontaneously or after
      mechanical trauma, (3) existence of localized esophageal strictures, (4) lack of
      concurrent chronic cutaneomucous lesions. Two patients presented with thymoma.
      Histologic examination showed evidence of mucosal blistering, in the absence of
      significant inflammatory lesions. Altered cell-cell adhesion was suggested by the
      reduced number of desmosomes on ultrastructural examination and the decreased
      expression of immunoreactive intercellular adhesion molecule E-cadherin.
      CONCLUSION: Chronic esophagitis dissecans likely represents a hitherto
      unrecognized clinicopathologic entity and must be added to the causes of chronic
      dysphagia.

PMID- 9013169
TI  - Transpapillary stenting of proximal biliary strictures: does biliary
      sphincterotomy reduce the risk of postprocedure pancreatitis?
AB  - BACKGROUND: Pancreatitis after biliary stenting is a rare complication. To reduce
      this risk, some endoscopists routinely perform biliary sphincterotomy before
      stenting, but the value of this practice is not established. METHODS: The
      incidence of pancreatitis was reviewed in patients undergoing biliary stenting
      with and without a biliary sphincterotomy. RESULTS: Postprocedure pancreatitis
      occurred in 4 of 83 (4.8%) patients treated with transpapillary biliary stents.
      Patients with proximal biliary strictures were at significantly increased risk
      for postprocedure pancreatitis (4 of 24) versus those with distal or no
      strictures (0 of 59) (p = 0.006). The four patients with pancreatitis after
      stenting had not undergone sphincterotomy. Of those treated conservatively, two
      cases were graded severe (one fatal), and one was mild. The other patient was
      markedly symptomatic from pancreatitis, but improved dramatically after treatment
      with a needle-knife sphincterotomy done within 24 hours of the original ERCP.
      CONCLUSION: The risk of pancreatitis following transpapillary biliary stenting is
      increased in patients with proximal biliary strictures. Such lesions (malignant
      or benign) may serve as a fulcrum, leading to medial deflection of the stent and
      compression of the pancreatic orifice. The hypothesis that sphincterotomy may
      decrease the risk of biliary stent-induced obstructive pancreatitis should be
      tested in patients with proximal biliary strictures.

PMID- 9013170
TI  - Analysis of occluded pancreatic stents and juices in patients with chronic
      pancreatitis.
AB  - BACKGROUND: Pancreatic stents may occlude with time, and there is little
      information available on the nature of the clogging process. METHODS: We analyzed
      the contents of occluded pancreatic polyethylene stents in nine patients with
      chronic pancreatitis. In the same patients, the protein patterns in the
      corresponding pancreatic juices were analyzed. The stents had been in place for a
      mean of 9 weeks (range 2 to 17). RESULTS: All stents were occluded at both ends,
      especially around side holes, with thick creamy-white precipitate. The average
      dry weight of occluding debris was 3 mg per 3.25 cm 10F stent. Total protein
      content was 50% (SD 16.3) and total calcium 0.8% of dry weight (SD 0.6). Light
      microscopy showed that proteinaceous material completely filled the stent lumen.
      Yeasts and plant material were seen in two stents. A variable number of bacteria
      of mixed species, sometimes in clumps, were patchily scattered in the protein
      matrix. Cultures of stent contents grew several species of Gram-positive and
      negative bacteria. Scanning and transmission electron microscopy showed an
      amorphous protein matrix in all stents, arranged as a network in some areas, but
      in layers in other areas. Sodium dodecylsulfate polyacrimide gel electrophoresis
      showed that protein patterns of stent contents were remarkably different from the
      protein patterns of the juice samples of the same patient. A 66 kD band,
      identified as albumin, appeared in the protein patterns of stent content, whereas
      it was lacking in most juice samples. CONCLUSIONS: Adherence of protein,
      especially albumin, plays an important role in the process of pancreatic stent
      clogging. Other factors, such as bacteria, refluxed duodenal contents, and
      calcium seem to be of less importance.

PMID- 9013171
TI  - Pancreatic ductal changes in HIV-infected patients.
AB  - BACKGROUND: AIDS-related sclerosing cholangitis occurs in patients with advanced
      immunodeficiency, but ductal pancreatic alterations have not been evaluated in
      large series. METHODS: Twenty-nine consecutive patients with a mean age of 33
      years underwent ERCP for biliary work-up. Complete pancreatography was obtained
      in 28 patients. Serum levels of amylase were increased in 17 patients prior to
      ERCP. The mean duration of HIV infection was 6.1 years (range 3 to 10 years).
      RESULTS: Fifteen patients (53.6%) had pancreatographic changes classified
      according to the Cambridge classification (stage 1, 4 cases; stage 2, 7 cases;
      stage 3, 4 cases). Dilatations, irregularities, short stenoses of the main
      pancreatic duct, and irregularities of side branches were the most frequent
      abnormalities. Fourteen of these 15 patients (93.3%) had cholangitis and a CD4
      cell count of less than 60 per cubic millimeter. Risk factors for pancreatic
      damage were similar in patients with and without pancreatographic changes.
      Opportunistic infection occurred in 14 of 15 patients with pancreatographic
      changes (candida, cytomegalovirus, cryptosporidia, microsporidia, and
      mycobacteria). CONCLUSION: Abnormal pancreatographies were found in about half of
      the HIV-infected patients who underwent ERCP. The pancreatographic features were
      suggestive of chronic pancreatitis and were closely related to the presence of
      AIDS-related sclerosing cholangitis.

PMID- 9013172
TI  - Complications following percutaneous endoscopic gastrostomy and subsequent
      catheter replacement in children and young adults.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy has gained wide acceptance for
      patients who require prolonged tube feeding support. We sought to identify
      complications and associated risk factors of endoscopic gastrostomy and
      subsequent catheter replacement in pediatric patients. METHODS: Medical records
      were reviewed for 137 patients. Odds ratios were calculated for complications
      related to patient age, weight, weight-for-age Z score, and principal diagnosis.
      RESULTS: Seventeen patients (12.4%) developed significant complications after
      gastrostomy: cellulitis occurred in 10 patients (7.3%); other complications
      included gastrocolic fistula (2), duodenal hematoma (1), complicated
      pneumoperitoneum (1), necrotizing fasciitis (1), gastric perforation (1), and
      catheter migration (1). Patients with cancer had significantly greater odds for
      developing a wound infection, and patients with AIDS had significantly greater
      odds for total complications. A trend toward increased wound infection was
      observed in patients with cardiac disease. Age, weight, and weight-for-age Z
      score were not associated with adverse outcome. Two complications occurred in 85
      patients (2.4%) after gastrostomy catheter replacement. CONCLUSIONS: Pediatric
      patients with cancer and AIDS are at increased risk for complications after
      endoscopic gastrostomy regardless of age, weight, or nutritional status.
      Infrequent yet life-threatening complications may occur after replacement of
      initial gastrostomy catheter.

PMID- 9013173
TI  - Endoscopic nasogastric-jejunal feeding tube placement in critically ill patients.
AB  - BACKGROUND: Historically, placement of small bowel nasoenteric feeding tubes in
      the critically ill patient has been difficult because of lack of bedside
      fluoroscopy, inadequately designed endoscopic tubes, or failure of the tube to
      spontaneously pass into the duodenum following placement. METHODS: We followed-up
      54 consecutive critically ill patients who had a combined nasogastric-jejunal
      feeding tube placed at the bedside using a new endoscopic, nonfluoroscopic method
      of placement. Data were obtained on the placement procedure, outcomes, and
      complications that followed. RESULTS: Tubes were successfully placed in 94% of
      the patients in an average time of 12 minutes. Negative outcomes included the
      following: inadvertent removal by patient or staff (21%), intolerance to tube
      feeding (14%), clogging (9%), kinking (6%), and cracking at the tube adapter
      (11%). The duration of the tube following placement ranged from 1 to 42 days,
      with an average of 9 days. CONCLUSION: The combined tubes were easy to place
      endoscopically. The endoscopic, nonfluoroscopic method of placing feeding tubes
      can be performed at the bedside and allows for gastric decompression and enteral
      feeding to be rapidly and efficiently achieved, which is particularly useful for
      intubated patients in an intensive care setting. Negative outcomes should
      decrease by avoidance of inadvertent tube removal and by improved tube
      maintenance and materials.

PMID- 9013174
TI  - Treatment of achalasia by injection of botulinum toxin under endoscopic
      ultrasound guidance.

PMID- 9013175
TI  - Percutaneous endoscopic gastrostomy/jejunostomy (PEG/PEJ) tube placement: a novel
      approach.

PMID- 9013176
TI  - Pericardioesophageal fistula associated with metallic stent placement.

PMID- 9013177
TI  - Endoscopic transrectal drainage of a diverticular abscess.

PMID- 9013178
TI  - Low-grade gastric mucosa-associated lymphoid tissue lymphoma revealed by a
      bleeding Dieulafoy's ulceration.

PMID- 9013179
TI  - Blue rubber bleb nevus syndrome: endoscopic removal of the gastrointestinal
      hemangiomas.

PMID- 9013180
TI  - Direct button percutaneous endoscopic jejunostomy: successful placement in a
      patient with severe malnutrition and previous gastric resection.

PMID- 9013186
TI  - Modified Soehendra stent extractor.

PMID- 9013184
TI  - Gastrointestinal endoscopy.

PMID- 9013182
TI  - Superficial esophageal carcinoma detected on extensive esophageal varices before
      endoscopic injection sclerotherapy.

PMID- 9013185
TI  - Screening for colorectal cancer: confuting the refuters.

PMID- 9013188
TI  - The rule of three in esophageal dilation.

PMID- 9013183
TI  - The role of endoscopic ultrasound in the evaluation and management of foregut
      duplications.

PMID- 9013187
TI  - Obtaining contrast-free bile during ERCP.

PMID- 9013181
TI  - Rescuing the retractable injection needle through the duodenoscope.

PMID- 9013189
TI  - Esophageal tattoo from ingested capsule.

PMID- 9013190
TI  - Are the reactive oxygen-derived species (ROS) interactive properties of the many
      therapeutic drugs from various categories pertinent to their beneficial effects?
AB  - Many pathologic states are known to involve the generation of reactive oxygen
      species, (ROS). It is not known at present to what extent these phenomena are due
      to ROS formation, or if their formation is a result of the disease. Many
      therapeutic drugs either scavenge ROS or inhibit their formation. The purpose of
      this review is to match the drugs used for certain diseases with their anti-ROS
      actions. This attempted correlation is made to try to give an answer to the title
      question.

PMID- 9013191
TI  - N-(Hydroxymethyl) melamines.
AB  - 1. The N-(hydroxymethyl) melamines are analogs of the antitumor agent
      hexamethylmelamine (HMM) which do not require bioactivation to exert their
      antitumor effects. 2. Trimelamol (N2,N4,N6-trihydroxymethyl-N2,N4,N6
      trimethylmelamine; TM) was developed as a water-soluble antitumor agent for
      intravenous administration. 3. Phase I and II trials of TM showed promising
      activity versus platinum-refractory ovarian cancer, but unfortunately further
      clinical development was halted due to formulation difficulties. 4. Stable
      analogs of TM were synthesized in an effort to overcome this shortcoming and
      these were evaluated in a number of in vitro and in vivo studies. 5. While the
      stable analogs showed good in vitro cytotoxicity in tumor cell lines, only one
      analog, CB7646 [bis-N-(hydroxymethyl)trimethylmelamine], showed comparable in
      vivo antitumor activity to that seen for TM. 6. Both TM and CB7646 were curative
      in human ovarian and breast cancer xenograft models, including the HX110P ovarian
      cancer xenograft with acquired resistance to carboplatin. 7. As CB7646 possesses
      favorable formulation characteristics, relating to its superior stability over
      that for TM, it is currently being developed for phase I clinical trial. 8. The N
      (hydroxymethyl) melamines are capable of overcoming many forms of drug
      resistance, based on data obtained in in vitro and in vivo studies, and thus show
      promise as agents in the treatment of heavily pretreated, refractive tumors.

PMID- 9013192
TI  - Preclinical studies on the broad-spectrum neuropeptide growth factor antagonist
      G.
AB  - 1. Antagonist G is a broad-spectrum neuropeptide growth factor antagonist that
      inhibits the growth of small cell lung cancer (SCLC) cells both in vitro and in
      vivo. 2. Antagonist G is metabolized in peripheral tissues by a chymotrypsin-like
      serine carboxypeptidase causing C-terminal deamidation and removal of the
      methionine residue. 3. The metabolites of Antagonist G retain neuropeptide
      antagonist properties and are thought to contribute to the parent peptide's
      antitumor activity. 4. Pharmacokinetic studies following systemic (IP)
      administration to nude mice revealed that the tissue distribution of Antagonist G
      is likely to be determined by vascular permeability. 5. Preclinical toxicology
      studies have been completed, and we have now started a phase I clinical trial.

PMID- 9013193
TI  - Zonation of cytochrome P450 expression, drug metabolism and toxicity in liver.
AB  - 1. In this brief review, current concepts on the zonated expression of liver
      genes involved in phase I and phase II drug metabolism will be presented. 2. It
      is now clear that the P450 isoforms involved in drug activation and steroid
      metabolism exhibit a particularly prominent zonation, with high expression and
      preferential induction in hepatocytes of the perivenous region. 3. In comparison,
      among the phase II enzymes, the perivenous dominance of glutathione transferases
      and UDP-glucuronyltransferases is less prominent, and glutathione peroxidase
      displays an opposite, periportally dominated pattern. 4. The factors regulating
      the zonated expression of these and other liver genes are poorly known. We have
      observed that pituitary-dependent hormones, particularly growth hormone,
      extinguish the periportal (upstream) expression of several CYP forms (CYP2B1/2
      and CYP3A1/2). However, the zonation of other CYP forms (CYP2A, CYP2E1, CYP 2C11
      and CYP 2C12) is less affected, suggesting that hormonal factors are important,
      but that the zonation of each P450 form is orchestrated by a different set of
      factors. 5. Because many hepatotoxins cause zone-specific damage, further
      unravelling the factors governing zonal expression of phase I and phase II
      enzymes will be necessary to clarify how drug-specific patterns of liver damage
      arise.

PMID- 9013194
TI  - The alpha-adrenoceptor-mediated actions of chloroethylclonidine.
AB  - 1. Chloroethylclonidine (CEC) has an affinity for all 6 subtypes of alpha
      adrenoceptor, but binds irreversibly particularly to alpha 1B-, alpha 1D-, alpha
      2C-, and alpha 2A/D-adrenoceptors. 2. Functionally, CEC behaves as an
      irreversible alpha 1-adrenoceptor antagonist, reducing the maximum response to
      noradrenaline (NA), and shows subtype selectivity in that alpha 1A-adrenoceptors
      are relatively insensitive to CEC. CEC also behaves as an irreversible alpha 2
      adrenoceptor agonist, both prejunctionally in the rat vas deferens and
      postjunctionally in the dog saphenous vein. 3. In the rat aorta, CEC does not
      produce direct contractions, but following exposure to CEC concentrations of NA
      of 10 microM and above produce contractions resistant to alpha 1- and alpha 2
      adrenoceptor blockade. We have investigated this phenomenon in detail. 4.
      Receptor protection experiments were carried out in the rat aorta, in which the
      protecting agent was present prior to and during exposure to CEC. The component
      of the contraction to NA resistant to alpha-blockade was still present following
      receptor protection with the alpha 1-adrenoceptor antagonist prazosin, but absent
      following receptor protection with NA and reduced following receptor protection
      with alpha 2-adrenoceptor antagonists. The resistant response may represent an
      irreversible agonist interaction between CEC, NA, and normally silent alpha 2
      adrenoceptors, that cannot be affected by subsequent competitive antagonism, but
      that can be prevented by receptor protection with the agonist NA prior to CEC. 5.
      CEC has two major classes of action at alpha-adrenoceptors: irreversible
      antagonism at alpha 1-adrenoceptors, and irreversible agonism at alpha 2
      adrenoceptors. Both actions can be demonstrated in the rat aorta.

PMID- 9013195
TI  - Effect of amphotericin B associated with a lipid emulsion on the oxidative burst
      of human polymorphonuclear leukocytes.
AB  - 1. Despite its toxicity, amphotericin B (AB) continues to be the drug of choice
      for the treatment of systemic fungal infection. The drug acts on several cell
      types, including polymorphonuclear leukocytes (PMN), where it inhibits the
      oxidative burst of cells submitted to several stimuli. 2. It was previously shown
      that the association of AB with a triglyceride-rich emulsion that physiologically
      mimics chylomicrons reduces toxicity. 3. We found that the association of AB with
      a triglyceride-rich emulsion reduces the loss of PMN viability produced by the
      drug. 4. The inhibition of the PMN oxidative burst triggered by phorbol 12
      myristate 13-acetate (PMA) and opsonized zymosan (OZ) also was decreased by the
      association of the drug with this lipid emulsion. 5. Delivery of AB in a lipid
      emulsion may be of advantage in the treatment of immunosuppressed patients.

PMID- 9013196
TI  - Effects of thyrotropin-releasing hormone and its analogue, NS-3, on blood
      pressure, heart rate, and serum catecholamine levels in rats.
AB  - 1. Thyrotropin-releasing hormone (TRH) and its metabolically stable analog NS-3
      (montirelin hydrate; [3R, 6R]-6-methyl-5-oxo-3-thiomorpholinyl carbonyl-L
      histidyl-L-prolinamide tetrahydrate) produced dose-dependent increases in blood
      pressure, heart rate, and the levels of serum noradrenaline and adrenaline in
      rats. 2. The pressor and tachycardiac effects and increases in serum
      catecholamine levels caused by NS-3 were longer lasting, but not more potent than
      those caused by TRH. 3. NS-3 did not change the blood pressure, heart rate, or
      the serum catecholamine levels in either pithed or hexamethonium-pretreated rats.

PMID- 9013197
TI  - Antiestrogenic compounds inhibit estrogen-induced expressions of basic fibroblast
      growth factor and its mRNA in well-differentiated endometrial cancer cells.
AB  - 1. The levels of basic fibroblast growth factor (FGF) expression and secretion
      and its messenger ribonucleic acid (mRNA) expression in well-differentiated
      endometrial cancer (Ishikawa) cells were significantly increased by estradiol. 2.
      This increase was significantly inhibited by tamoxifen, progestins (progesterone,
      medroxyprogesterone acetate [MPA], and 17 alpha-hydroxyprogesterone), and to some
      extent danazol, but not by terahydrocortisol and hydrocortisone. 3. Estrogen
      might stimulate the basic FGF secretion of endometrial cancer cells, at least for
      neovascularization, and antiestrogenic compounds may inhibit the estrogen-induced
      event.

PMID- 9013198
TI  - Effect of prostaglandin E1 on the rat inner ear microvascular thrombosis.
AB  - 1. The effect of prostaglandin E1 was investigated with a two-rat model of
      hearing disturbance and equilibrium dysfunction associated with inner ear
      microvascular thrombosis. 2. The inner ear microvascular thrombosis was induced
      by photochemical reaction between Rose Bengal and transmural green light (540
      nm). Photochemical reaction causes endothelial injury followed by platelet
      adhesion, aggregation, and formation of a platelet- and fibrin-rich thrombus. 3.
      Under anesthesia, the cochlea or the vestibule was irradiated with green light to
      induce hearing disturbance or equilibrium dysfunction. 4. In the hearing
      disturbance model, a compound cochlear nerve action potential was recorded by
      electrocochleography every minute after the beginning of photoirradiation in the
      presence of Rose Bengal. 5. In the equilibrium dysfunction model, the
      photoirradiation was applied for 10 min after Rose Bengal administration. The
      behavior of rats was observed in the swimming test, and nystagmus was observed 24
      hr after the end of photoirradiation. 6. Prostaglandin E1 significantly (P <
      0.05) prolonged the time required to suppress the action potential. In the
      swimming test, 3 of the 6 animals treated with prostaglandin E1 did not rotate
      about their longitudinal axes (equilibrium dysfunction) and the duration of well
      balanced swimming was significantly prolonged (P < .001). Prostaglandin E1
      significantly (P < 0.05) suppressed the appearance of nystagmus. 7. In
      conclusion, prostaglandin E1 potentially prevents hearing disturbance and
      equilibrium dysfunction due to inner ear microvascular disorders.

PMID- 9013200
TI  - The mechanism of action of KBT-3022, a new antiplatelet agent.
AB  - 1. The mechanism of action of a new antiplatelet agent, KBT-3022 (ethyl 2-[4,5
      bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and its active main
      metabolite, desethyl KBT-3022, was investigated. 2. KBT-3022 and desethyl KBT
      3022 inhibited cyclooxygenase from ovine seminal gland with IC50 values of 0.69
      and 0.43 microM, respectively. 3. At concentrations higher than those required
      for cyclooxygenase inhibition, desethyl KBT-3022 inhibited cAMP
      phosphodiesterase, specific binding of U46619, and release of phosphatidic acid
      from thrombin-stimulated platelets. 4. Oral administration of KBT-3022 inhibited
      the production of thromboxane B2 during blood coagulation more potently than the
      production of 6-keto-prostaglandin F1 alpha from aortic strips in guinea pigs. 5.
      These findings suggest that KBT-3022 may inhibit platelet activation principally
      via the inhibition of cyclooxygenase by desethyl KBT-3022.

PMID- 9013201
TI  - Inhibitory effects of caffeine on Ca2+ influx and histamine secretion independent
      of cAMP in rat peritoneal mast cells.
AB  - 1. Caffeine did not evoke Ca2+ mobilization and histamine secretion. 2. Caffeine,
      as well as other methylxanthines but not forskolin or 8 bromo-cAMP, inhibited
      Ca2+ responses from compound 48/80. 3. Evoked histamine secretion was severely
      reduced by caffeine but not by cAMP analogs. 4. In beta-escin-permeabilized
      cells, caffeine did not affect resting and IP3-stimulated 45Ca2+ release, but it
      inhibited Ca(2+)-induced histamine secretion. 5. These results indicate that
      caffeine inhibits Ca2+ influx and Ca2+ efficacy in the secretory apparatus
      independent of cAMP, resulting in the inhibition of secretagogs-evoked histamine
      secretion from rat mast cells.

PMID- 9013199
TI  - Responses of catecholamines, renin-angiotensin system, and atrial natriuretic
      peptide to exercise in untrained men and women.
AB  - 1. Plasma norepinephrine (NE), epinephrine (E), renin activity (PRA), angiotensin
      II (ATII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured
      in 20 male and 15 female subjects during submaximal treadmill test. 2. Exercise
      duration was not different between the two groups (male vs. female: 13.4 +/- 0.8
      min vs. 11.6 +/- 0.7 min, ns). Female subjects had higher heart rate during
      exercise, while systolic blood pressure at peak exercise was higher in male
      subjects. 3. Plasma NE, E, ANP, and ATII responses were comparable between male
      and female subjects, but PRA both at rest and during exercise and ALD at rest
      were significantly higher in male subjects. 4. Cardiac responses to submaximal
      exercise were different between male and female subjects, but neurohormonal
      responses were comparable between the two groups except for the high PRA at rest
      and during exercise and high plasma ALD at rest in male subjects.

PMID- 9013202
TI  - Low concentrations of caffeine raise intracellular calcium concentration only in
      the presence of extracellular calcium in cultured molluscan neurons.
AB  - 1. The effects of low concentrations of caffeine (100 and 300 microM) on the
      intracellular calcium concentration [Ca2+]i in four cultured, identified neurons
      of the pond snail Lymnaea stagnalis (L) were investigated. 2. Intracellular CA2+
      levels in these neurons were measured with the cell-permeable Ca2+ indicator Fura
      2/AM, both in the presence and absence of extracellular Ca2 (o-Ca2+/EGTA). 3. In
      the presence of Ca2+ in the external medium, caffeine was found to induce a
      substantial elevation in the free [Ca2+]i in all cell types. 4. In some cases,
      the rise in [Ca2+]i was found to be both time- and concentration-dependent. 5.
      Low doses of caffeine did not produce any appreciable rise in [Ca2+]i in the
      absence of Ca2+ in the external medium, but calcium was still available from
      stores, as clinical concentrations of halothane rose [Ca2+]i in the absence of
      extracellular calcium. 6. These results indicate that the actions of caffeine,
      when applied at low concentrations, are dependent on extracellular calcium.

PMID- 9013203
TI  - Inhibition of platelet activation by MM-706, a stable carbacyclin analog, in the
      conscious rat.
AB  - A new stable analog of carbacyclin, 13,14-dihydro-15,16,17,18,19,20-hexanor-14-(1
      hydroxycyclohexyl) carbacyclin, identified as MM-706, was investigated in vivo in
      the conscious rat. MM-706 as single bolus (200 micrograms/kg, equivalent to 546
      nmol/kg) prevented the reduction of circulating platelets induced by adenosine
      diphosphate (ADP) (1 mumol/kg as IV bolus). 2. A similar effect on free platelet
      numbers also was observed with iloprost (20 and 200 micrograms/kg IV bolus).
      However, MM-706 did not induce any significant variation of mean arterial blood
      pressure (MABP) or heart rate, unlike iloprost, which reduced MABP within 10 min
      of administration. 3. In conclusion, MM-706 is effective in interfering with in
      vivo platelet activation induced by ADP without influencing other cardiovascular
      parameters, such as arterial pressure and heart rate.

PMID- 9013204
TI  - Protection from acetaminophen-induced liver damage by the synergistic action of
      low doses of the poly(ADP-ribose) polymerase-inhibitor nicotinamide and the
      antioxidant N-acetylcysteine or the amino acid L-methionine.
AB  - 1. An array of therapeutically used analgetic and antirheumatic drugs cause
      severe liver damage. The present study investigates the hepatoprotective effects
      of inhibitors of NAD-dependent adenoribosylation reactions and of antioxidants in
      analgesic-induced hepatic injury. 2. Male NMRI mice were treated PO with 500
      mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate
      transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in
      serum. 3. The acetaminophen-induced release of both GOT and GPT from injured
      liver cells could be inhibited in a dose-dependent manner, when mice were
      injected additionally either with increasing amounts (from (25 mg/kg to 100 mg/kg
      i.p.) of the PARP-inhibitor nicotinamide, with increasing amounts (from 25 mg/kg
      to 100 mg/kg i.p.) of the antioxidant N-acetylcysteine, or with increasing
      amounts (from 50 mg/kg to 300 mg/kg i.p.) of the amino acid L-methionine. 4. A
      combination of both nicotinamide and N-acetylcysteine (at the low dose of 12.5
      mg/kg i.p. each) results in a complete protection from acetaminophen-induced
      release of GOT and GPT from injured liver cells. 5. A combination of both L
      methionine and N-acetylcysteine or nicotinamide (at the low dose of 12.5 mg/kg IP
      each) resulted also in complete protection from acetaminophen-induced release of
      GOT and GPT.

PMID- 9013205
TI  - Synthesis of achatin-I (Gly-D-Phe-L-Ala-L-Asp) analogs having
      dehydrophenylalanine or aminoisobutyric acid residue at position 2, and their
      effects on Achatina giant neurons.
AB  - 1. Achatin-I (Gly-D-Phe-L-Ala-L-Asp), a neuroactive tetrapeptide having a D
      phenylalanine residue, has been proposed to be an excitatory neurotransmitter of
      Achatina giant neurons. It was revealed that the D-Phe2 residue is essential for
      bioactivity of achatin-I, which seems to adopt beta-turn conformation. In the
      present study, in order to investigate the structure-activity relationships of
      achatin-I and its derivatives, the two highly constrained analogs of achatin-I,
      [delta ZPhe2]achatin-I (Gly-delta ZPhe-L-Ala-L-Asp) (delta ZPhe: (Z)-alpha,beta
      dehydrophenylalanine) and [Aib2]achatin-I (Gly-Aib-L-Ala-L-Asp) (Aib: alpha
      aminoisobutyric acid), were synthesized, and their effects on the two
      identifiable Achatina giant neuron types, PON (periodically oscillating neuron)
      and v-RCDN (ventral-right cerebral distinct neuron), were examined in comparison
      with those of achatin-I under voltage clamp. 2. Achatin-I (n = 6), ejected onto
      the neurone by brief pneumatic pressure (2 kg/cm2, 400 ms, 10(-3) M, at 10-min
      intervals), produced an inward current (Im) on PON. The Iin value (mean +/- SEM)
      was 0.44 +/- 0.03 nA. The interval between the achatin-I ejection and the Iin
      peak was 14.74 +/- 3.15 s (n = 6). [delta ZPhe2]achatin-I (n = 6) and
      [Aib2]achatin-I (n = 6) had no effect on this neuron type. 3. On the other hand,
      achatin-I (n = 10) and [delta ZPhe2]-achatin-I (n = 10), ejected by brief
      pressure, produced an Iin on v-RCDN. The Iin values were 0.85 +/- 0.07 nA for
      achatin-I and 0.48 +/- 0.05 nA (p < 0.01, compared with that of achatin-I by
      Student's t-test for paired data) for [delta ZPhe2]achatin-I. The intervals
      between the compound ejection and the Iin peak were 5.95 +/- 0.33 s for achatin-I
      and 8.70 +/- 0.81 s (p < 0.05, compared with that of achatin-I) for [delta
      ZPhe2]achatin-I. [Aib2]achatin-I (n = 10) had no effect on this neuron type.

PMID- 9013206
TI  - Scavenging of hypochlorous acid by carvedilol and ebselen in vitro.
AB  - 1. The antihypertensive drug carvedilol and the antiinflammatory selenoorganic
      compound ebselen were tested for their ability to react with the reactive oxygen
      species hypochlorous acid (HOCl) in vitro. 2. Carvedilol scavenges HOCl at a rate
      sufficient to protect a model molecule catalase against inactivation by HOCl. 3.
      Ebselen was resistant to HOCl when its glutathione-peroxidase mimetic property
      was compared with that of glutathione peroxidase.

PMID- 9013207
TI  - The mechanisms of action of antiprotozoal and anthelmintic drugs in man.
AB  - The mechanisms of action of antiprotozoal and anthelmintic drugs are reviewed
      according to: (1) drugs interfering with metabolic processes; (2) drugs
      interfering with reproduction and larval physiology; and (3) drugs interfering
      with neuromuscular physiology of parasites.

PMID- 9013208
TI  - Effects of TYB-2285 on the accumulation of eosinophils in the airway induced by
      antigen exposure in actively sensitized brown Norway rats.
AB  - 1. The effect of TYB-2285 on the antigen-induced accumulation of eosinophils into
      the airway was investigated in two models (inhalant sensitization and noninhalant
      sensitization) using Brown Norway (BN) rats. 2. In the method of inhalant
      sensitization, BN rats were sensitized by weekly exposure to ovalbumin (OA). The
      accumulation of eosinophils was inhibited by the oral administration of TYB-2285
      for the first 2 days of each sensitization in a dose-dependent manner. 3. With
      noninhalant sensitization, BN rats were sensitized by i.m. injection of OA and
      i.p. injection of killed Bordetella pertussis. The accumulation of eosinophils
      was inhibited by TYB-2285 in a dose-dependent manner, when TYB-2285 is given p.o.
      5 mm before and 5 hr after the antigen exposure. Moreover, this accumulation of
      eosinophils was inhibited by a single administration of TYB-2285 5 hr after the
      antigen exposure, presumably when the mast cell degranulation was already
      finished. 4. In the method with noninhalant sensitization, the accumulation of
      eosinophils was not inhibited by mast cell stabilizers such as ketotifen,
      tranilast, or DSCG. 5. The present study demonstrates that TYB-2285, unlike other
      mast cell stabilizers, inhibits the antigen-induced accumulation of eosinophils
      into the airway. It also suggests that this drug might be effective in asthmatic
      patients.

PMID- 9013209
TI  - Effect of TYB-2285 on lung anaphylaxis in actively sensitized rats.
AB  - 1. We examined the effect of TYB-2285 on the acute phase and the late phase of
      lung anaphylaxis in rats. 2. TYB-2285 (3-30 mg/kg PO) inhibited antigen-induced
      bronchoconstriction and TxB2 production during the acute phase of lung
      anaphylaxis in a dose-dependent manner. 3. Ketotifen fumarate (30 mg/kg p.o.)
      inhibited bronchoconstriction and TxB2 production less potently than TYB-2285. 4.
      TYB-2285 (30 mg/kg p.o.) inhibited the accumulation of neutrophils during the
      late phase of lung anaphylaxis significantly without a significant change in
      total cells. 5. Hydrocortisone acetate (100 mg/kg p.o.) inhibited the
      accumulation of total cells as potent as neutrophils.

PMID- 9013210
TI  - Effect of TYB-2285 on passive cutaneous anaphylaxis in rats.
AB  - 1. TYB-2285 (1-30 mg/kg p.o.) inhibited ovalbumin (OA)- and dinitrophenyl-Ascaris
      (DNPAs)-induced passive cutaneous anaphylaxis (PCA) in a dose-dependent manner.
      2. The ED50 of TYB-2285 and ketotifen fumarate on OA-induced PCA were 0.5 and 3.9
      mg/kg, respectively. The ED50 of TYP-2285 and amlexanox on DNP-As-induced PCA
      were 3.5 and 0.9 mg/ kg, respectively. 3. TYB-2285 (3-30 mg/kg p.o.) inhibited
      histamine consumption at the PCA site. 4. Unlike cyproheptadine or amlexanox, TYB
      2285 (30 mg/kg p.o.) did not inhibit histamine-, serotonin-, ascites-, 48/80-, or
      A23187-induced capillary permeability. It inhibited dextran-induced capillary
      permeability slightly. 5. These results demonstrate that TYB-2285 inhibits PCA by
      inhibiting histamine release, although it does not inhibit capillary
      permeability.

PMID- 9013211
TI  - Modulatory effect of 8-iso-PGE2 on platelets.
AB  - 1. 8-Iso-PGE2 induced either reversible or irreversible aggregation of platelets
      in human platelet-rich plasma (PRP) or in the suspension of washed platelets
      (WP). The values of EC50 for irreversible aggregation in PRP and WP were 4 and 2
      microM, respectively. 2. In rabbit PRP, 8-iso-PGE2 (0.1-100 microM) itself did
      not induce or induced only reversible aggregation. 3. 8-Iso-PGE2 (0.1-20 microM)
      potentiated adenosine diphosphate-(ADP) induced platelet aggregation in both
      human and rabbit. The same effect also was found for adrenaline-induced platelet
      aggregation in rabbit. 4. The lower concentrations (0.2-0.5 microM) of 8-iso-PGE2
      decreased, and higher concentrations (1-2 microM) increased platelet aggregating
      factor- (PAF) induced aggregation in human PRP. In rabbit PRP, 8-iso-PGE2 (0.02
      200 microM) had only a decreasing effect on PAF-induced aggregation. 5. The
      results suggest that low concentrations of 8-iso-PGE2 can amplify or weaken
      platelet aggregation induced by various aggregatory agents.

PMID- 9013212
TI  - Beta-adrenergic receptor and platelet inhibitory activities of a new series of
      trimetoquinol and related benzazepine analogs.
AB  - 1. A series of dimethoxy and methylenedioxy analogs of trimetoquinol (TMQ) and
      structurally related 7-membered ring benzazepines (BA) were evaluated for their
      pharmacological effects in beta-adrenergic (atria, trachea) and thromboxane
      A2/prostaglandin H2 receptor systems (aorta, platelets). 2. Results show that
      both the 6,7-dihydroxy (catechol) moiety of trimetoquinol and an intact
      tetrahydroisoquinoline nucleus are essential for maintaining potent beta
      stimulating and antithromboxane A2 activities. 3. By contrast, ring enlargement,
      as in the BA analogs, or masking of the catechol with dimethoxy or methylenedioxy
      functional groups enhanced the potency of inhibitors on thromboxane A2
      independent activation of human platelets induced by bacterial phospholipase C
      (PLC). 4. The selective blockade of this pathway by these compounds suggests that
      they may represent a new and novel class of antiplatelet drugs.

PMID- 9013213
TI  - Age-related changes in nociception, behavior, and monoamine levels in rats.
AB  - 1. Pain threshold, behavioral parameters, and monoamine levels were compared in
      two groups of rats: adult (12 months old) and old rats (25 months old). 2. No
      differences in nociception were found between the two groups using the tail-shock
      test. 3. Behavioral experiments with the holeboard test showed that locomotor
      activity and exploration activity were lower in aged animals, whereas no
      significant differences were found in emotivity. 4. Using high-performance liquid
      chromatography (HPLC) techniques, we found that serotonin and dopamine showed
      lower levels in the old group.

PMID- 9013215
TI  - Pharmacologic inhibition of twin-pulse facilitation of release of transmitter
      quanta at the mouse neuromuscular junction.
AB  - 1. The frequency (F,s-1) of miniature endplate potentials and the quantal content
      (m) of endplate potentials were simultaneously measured intracellularly at mouse
      diaphragm endplates in a bath solution that contained 0.6 mM Ca2+ ions and 5 mM
      Mg2+ ions. 2. Twin pulses at 4-ms intervals gave the quantal contents of the
      first (m1) and second (m2) responses. The ratio of m2/m1 was taken as an
      indicator of the temporal facilitation of the release of transmitter. 3. Lead
      ions (Pb2+; 10 microM), bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      (BAPTA; loaded for 60 min at 200 microM), and chlortetracycline (CTC; loaded for
      30 min at 80 microM) reduced the values of F and m2/m1. Pb2+ ions and CTC reduced
      the value of m, whereas BAPTA did not.omega-Agatoxin (omega AGT; 10 ng/ml)
      reduced the value of m without affecting F or m2/m1. 4. These results suggest
      that synaptic facilitation is modifiable by agents that can affect systems which
      buffer intracellular levels of Ca2+ ions.

PMID- 9013214
TI  - Caerulein may potentiate morphine-induced antinociception by cholecystokinin-A
      and/or cholecystokinin-B receptor mechanisms.
AB  - 1. The effects of a cholecystokinin agonist and antagonist on morphine
      antinociception in the tail-flick test have been evaluated. 2. The administration
      of different doses of caerulein (0.01, 0.05 and 0.1 mg/kg) 30 min prior to
      morphine (1.5, 3 and 6 mg/kg) increased the antinociception induced by morphine
      in mice. 3. In animals pretreated with cholecystokinin antagonists MK-329 (0.125
      and 0.25 mg/kg) and L-365,260 (0.125 and 0.25 mg/kg), the antinociceptive effect
      of morphine was not changed. However, high doses (0.5 mg/kg) of each antagonist
      potentiated the morphine response. 4. Low doses of cholecystokinin antagonists
      (0.125 and 0.25 mg/kg), that did not cause antinociception, when employed in
      combination with caerulein (0.05 mg/kg) decreased the response of morphine plus
      caerulein. 5. It is concluded that the cholecystokinin agonist caerulein
      potentiated the morphine response by stimulation of cholecystokinin-A and/or
      cholecystokinin-B receptors.

PMID- 9013216
TI  - Adult respiratory distress syndrome: a disorder in need of improved outcome.

PMID- 9013217
TI  - The effect of a pulmonary rehabilitation program on self-efficacy, perception of
      dyspnea, and physical endurance.
AB  - OBJECTIVE: To determine the effect of attendance at an outpatient pulmonary
      rehabilitation (OPR) program on changes in self-efficacy, perception of dyspnea,
      and exercise endurance in patients with chronic obstructive pulmonary disease
      (COPD). DESIGN: Single-group, pretest and posttest design. SETTING: A moderate
      sized, urban private hospital in western New York. PATIENTS: Sixty patients with
      a diagnosis of COPD. Their ages ranged from 35 to 82 years (mean +/- SD = 65 +/-
      0.75 years). OUTCOME MEASURES: Scores on the COPD Self-Efficacy Scale (CSES) and
      the Dyspnea Scale and distance walked (feet) on the 12-minute walking-distance
      test (12 MD). INTERVENTION: The OPR consisted of an educational component and
      exercise training. Methods to increase self-efficacy were integrated into the
      rehabilitation program. Preprogram and postprogram measurements were obtained on
      the CSES, the Dyspnea Scale, and the 12 MD. RESULTS: Paired t tests were used to
      examine the differences in mean scores between preprogram and postprogram results
      on the CSES, the Dyspnea Scale, and the 12 MD. There was a significant difference
      between preprogram and postprogram scores on the CSES (p < 0.01), the Dyspnea
      Scale (p = 0.01), and the 12 MD (p = 0.04). Pearson product moment correlations
      showed a significant negative correlation between scores on the CSES and scores
      on the Dyspnea Scale (r = -0.5566, p = 0.01) and a positive correlation between
      scores on the CSES and the 12 MD (r = 0.4293, p = 0.05). These results indicated
      that higher self-efficacy scores on the CSES were correlated with lowered
      perception of dyspnea and greater distances walked in 12 minutes. CONCLUSIONS: An
      OPR can improve self-efficacy or confidence in participants' ability to manage or
      avoid breathing difficulty. Improvement in self-efficacy also may be a factor in
      decreased perception of dyspnea and increased exercise endurance. Methods to
      increase self-efficacy expectations with education and exercise training provide
      an approach to assist persons with COPD to manage their breathing difficulty more
      effectively. Further studies using a randomized experimental, control design are
      needed to provide more conclusive direction with regard to effective methods in
      pulmonary rehabilitation.

PMID- 9013218
TI  - Dimensions of symptom distress in women with advanced lung cancer: a factor
      analysis.
AB  - OBJECTIVE: To explore the structure of symptom distress in women with advanced
      lung cancer. DESIGN: Descriptive. SETTING: Oncology clinics and private offices.
      SUBJECTS: Sixty women with advanced lung cancer (71% non-small-cell); the
      majority received palliative treatment (88%). OUTCOME MEASURES: Symptom Distress
      Scale and Karnofsky Performance Status Scale. METHOD: Factor analytic techniques
      (principal components, varimax rotation) to investigate combinations of all
      symptoms in the Symptom Distress Scale and combinations of serious symptoms.
      RESULTS: Fatigue, disruptions in outlook, frequent pain, and difficulties in
      sleeping were rated the most distressing and were the most prevalent serious
      disruptions. A four-factor solution for the symptom distress ratings explained
      63.3% of the variance and revealed groups of items representing emotional and
      physical suffering, gastrointestinal distress, respiratory distress, and malaise.
      Symptoms with a rating of serious distress were represented by five factors with
      emotional and physical suffering as separate factors. Symptoms were significantly
      related to Karnofsky Performance Status. CONCLUSIONS: Multiple symptoms formed
      distinct congregations of distress. Symptom control requires consideration as a
      multivariate approach.

PMID- 9013219
TI  - Effects of relaxation intervention in phase II cardiac rehabilitation:
      replication and extension.
AB  - OBJECTIVES: To examine the effects of progressive muscle relaxation and guided
      imagery on psychological and physiologic outcomes in adults with cardiovascular
      disease who were participating in a phase II cardiac rehabilitation program. To
      examine tension levels, practice patterns, and perceived helpfulness of the
      intervention reported by subjects. DESIGN: Prospective, quasi-experimental, with
      random group assignment within sites. Independent replication and extension of a
      study by Bohachik (1984). SETTING: Four midwestern hospital-based phase II
      cardiac rehabilitation programs. PATIENTS: Fifty patients who within the
      preceding 12 weeks had had acute myocardial infarction or coronary artery bypass
      surgery or both, studied during 6 weeks of participation in a phase II cardiac
      rehabilitation program. OUTCOME MEASURES: Psychological measures included state
      and trait anxiety scores on the State-Trait Anxiety Inventory and reported
      symptoms on the Symptom Checklist-90-Revised. Physiologic measures were resting
      heart rate and blood pressure. Subjective tension levels before and after home
      practice, practice patterns, and perceived helpfulness of the intervention were
      examined. INTERVENTION: Individual instruction session in progressive muscle
      relaxation and guided imagery at the phase II cardiac rehabilitation program,
      followed by daily home practice with audiotape instructions over a 6-week period.
      RESULTS: No statistical differences at the p < or = 0.05 level were found in
      state anxiety scores or reported symptoms at study exit. However, reductions in
      mean subscale scores for interpersonal sensitivity (t [19] = 2.11, p < or = 0.05)
      and depression (t [19] = 2.07, p < or = 0.05) by paired t tests were found for
      the relaxation group (RG). The two groups differed at study exit in resting heart
      rate (t [42] = -2.02, p < or = 0.05) by independent t tests and in systolic blood
      pressure (F [1,42] = 5.13, p < or = 0.05) by analysis of covariance. The RG had a
      mean resting heart rate 8.6 beats/min lower than that of the control group (CG)
      and also had within-group reductions in mean heart rate (t [19] = 2.09, p < or =
      0.05) by paired t tests. Contrary to expectation, the CG had a 3.5 mm Hg lower
      mean systolic blood pressure and within-group reductions in systolic (t [22] =
      3.02, p < 0.01) and diastolic (t [22] = 3.83, p < 0.01) blood pressure by paired
      t tests. CG subjects had a greater number of dose increases in cardiac
      medications and fewer dose reductions than did RG subjects, who also had a higher
      number of dose reductions. RG subjects reported frequent practice of the
      technique, rated it as helpful, and reported lower subjective tension levels
      after practice. CONCLUSIONS: Findings in this study did not support those of
      Bohachik (who reported lowered state anxiety and fewer somatization,
      interpersonal sensitivity, and depression symptoms). More instruction sessions on
      the relaxation method may have resulted in more positive outcomes. However, the
      within-group scores for interpersonal sensitivity and depression, the reduction
      in heart rate, and the receptivity of subjects to this intervention suggest that
      it may be a feasible and helpful adjunctive therapy for participants in a phase
      II cardiac rehabilitation program.

PMID- 9013220
TI  - Electrophysiologic mechanisms and electrocardiographic findings in
      atrioventricular-nodal reentrant tachycardia in a patient with the scimitar
      syndrome.
AB  - We describe a case of a 68-year-old man with scimitar syndrome and an
      atrioventricular-nodal reentrant tachycardia treated with adenosine. The emphasis
      in this article is on the electrophysiologic mechanism of and
      electrocardiographic (ECG) findings in this case of atrioventricular-nodal
      reentrant tachycardia.

PMID- 9013221
TI  - Laparoscopic surgery and its potential for medical complications.
AB  - Laparoscopic surgery is very popular among physicians and patients because this
      technique is associated with safety, shorter hospital stay, early return to
      normal activity, and cosmetic acceptance of the operative scar. Although the
      procedure involves minimal invasion and tissue damage, it has potentially serious
      complications, including cardiopulmonary effects that result mainly from
      hypercarbia and raised intraabdominal pressure caused by pneumoperitoneum.
      Absorbed carbon dioxide from the peritoneal cavity tends to cause acidosis.
      Leakage of the gas into tissue spaces may induce subcutaneous emphysema,
      pneumothorax, pneumomediastinum and pneumopericardium. Cardiac effects include
      arrhythmias, hypotension, cardiac arrest, gas embolism, pulmonary edema, and
      myocardial ischemia or infarction. Some of these effects, though rare, are
      serious and potentially fatal. Physicians should anticipate these problems in
      their patients undergoing laparoscopic procedures. This review discusses the
      technique of and physiologic considerations in laparoscopic surgery as well as
      its potential complications.

PMID- 9013222
TI  - Purpose of family photographs displayed in the pediatric intensive care unit.
AB  - OBJECTIVE: To investigate why parents frequently display family photographs on
      their children's beds in the intensive care unit (ICU). DESIGN: Questionnaire.
      SETTING: Tertiary-care pediatric ICU. SUBJECTS: Twenty-three parents who
      displayed pictures, 25 parents who did not, and 50 ICU nurses. OUTCOME MEASURE:
      Content analysis. RESULTS: Parents' stated primary reasons for displaying
      pictures were (1) to motivate the staff and (2) to comfort themselves. Parents
      not displaying photographs had not thought of displaying them, and the idea had
      not been suggested to them. Sixty-eight percent of the nurses surveyed reported
      that they invite parents to display photographs. CONCLUSIONS: We recommend that
      ICU staff consider discussing with parents the potential benefit of displaying
      photographs of their children. Pictures may open an avenue for communication,
      allow parents to express unspoken concerns, and give parents comfort or a goal to
      strive for and thus alleviate some of the stress associated with having a child
      in the ICU.

PMID- 9013223
TI  - Coronary thrombosis associated with inherited protein S deficiency: a case
      report.
AB  - Protein S deficiency (PSD) may be associated with thrombotic events, including
      venous and arterial thrombosis. Most commonly, superficial and deep venous
      thrombosis have been noted. We report a case of acute myocardial infarction
      resulting from coronary thrombosis in a young male with PSD.

PMID- 9013224
TI  - Haemophilus influenzae sepsis resulting from pneumonia.
AB  - Haemophilus influenzae is a pleomorphic gram-negative bacterium that causes a
      myriad of infections in both adults and children. The organism frequently causes
      respiratory infections in patients with obstructive lung disease but may on
      occasion cause invasive infections including pneumonia with bacteremia. We report
      the case of a patient with underlying lung disease and metastatic malignancy in
      whom sepsis related to pneumonia caused by H. influenzae developed.

PMID- 9013225
TI  - Non-Clostridium difficile nosocomial diarrhea in the intensive care unit.
AB  - It is assumed that most cases of nosocomial diarrhea are due to Clostridium
      difficile because of the widespread use of broad-spectrum antibiotic agents.
      Enteral tube feedings are another important cause of hospital-acquired diarrhea,
      especially in intensive care units (ICUs). We report the results of a recent
      survey of patients in the ICU with nosocomial diarrhea and describe an
      illustrative case. We conclude on the basis of this and a previous larger study
      that C. difficile diarrhea is very uncommon in enterally fed patients in the ICU;
      nosocomial diarrhea in the ICU is most commonly caused by enteral tube feedings.

PMID- 9013226
TI  - [Prognostic significance of histopathological findings (including lymphocyte
      infiltration) in renal cell carcinoma].
AB  - We compared the prognosis with the histopathological findings including
      intravenous invasion and lymphocytic infiltration inside or adjacent to the
      primary tumor in 50 renal cell carcinoma patients who underwent radical
      nephrectomy. We compared the primary tumor to intravenous invasion or metastases
      in histopathological findings. One-, three- and five-year survival rates for all
      patients were 91.7, 71.5 and 60.7%, respectively. Significant prognostic factors
      were tumor size, growth pattern, invasion of fat tissue into peripheral kidneys
      lymph nodes, distant metastases, intravenous invasion and tumor grade, especially
      lymph nodes and distant metastases (P < 0.001). Degree of lymphocytic
      infiltration inside or adjacent to primary tumor was divided into three groups.
      Five-year survival rates were 86.2% of the patients (n = 15) with apparent
      lymphocytic infiltration and 48.8% of the patients (n = 18) had few infiltrated
      lymphocytes. The patients with apparent lymphocytic infiltration showed a trend
      of better prognosis compared to the patients with few infiltrated lymphocytes (P
      < 0.1). Tumor grade was higher in 3 of the 28 patients with intravenous invasion
      and 6 of the 9 patients with distant metastases than in those with primary
      tumors. However, there was no significant correlation between prognosis and
      malignant potential of intravenous invasion or distant metastases.

PMID- 9013227
TI  - [Intermittent administration of 15-deoxyspergualin for acute on chronic rejection
      after renal transplantation].
AB  - We used 15-deoxyspergualin (DSG) to treat acute on chronic rejection (AOCR) in
      six kidney transplant recipients. DSG was administered intermittently at a dose
      of 200-300 mg per body every 2 or 4 weeks for more than 6 months. The efficacy of
      DSG was evaluated by the changes in serum creatinine values during the rejection
      therapy. Four (67%) of the six patients responded with the suppression of the
      increase in serum creatinine values. On the other hand, one patient did not
      respond at all and developed advanced pancytopenia. These findings suggested that
      intermittent administration of DSG would be efficient therapy on AOCR in the
      renal allografts if the patients were treated carefully to prevent severe side
      effects.

PMID- 9013228
TI  - [Studies on changes in the ratio of free to total PSA after endocrine treatment
      of prostate carcinoma].
AB  - The post-diagnostic changes in the free to total PSA ratio in the serum of
      patients with prostate carcinoma, after the initiation of endocrine treatment
      were examined. Two-week pretreatment with either chlormadinone acetate (100
      mg/day) or flutamide (375 ng/day) was administered orally to 14 patients with
      newly diagnosed advanced prostate carcinoma (clinical stage was C in 2, Dl in 1
      and D2 in 11). Then the LH-RH analogue was injected. Total and free PSA in the
      serum of these patients were measured every 4 weeks by the Ab bead PSA (Eiken)
      and the recently developed assay for free PSA by Eiken, respectively. The follow
      up period ranged from 3 to 9 months with a median of 6 months. Levels of both
      total and free PSAs decreased significantly following the endocrine treatment,
      while free to total PSA ratio at 4 to 16 weeks after the start of LH-RH analogue
      was increased significantly compared to the pretreatment level (p < 0.05). These
      findings suggest that the rate of decrease of complex PSA during the first 4
      months after the beginning of treatment may exceed that of free PSA in the serum
      of patients with advanced prostate carcinoma initially treated with endocrine
      therapy.

PMID- 9013229
TI  - [Clinical study of testicular cancer].
AB  - Since April 1986, a prospective clinical trial for testicular cancer has been
      underway by our Nara Uro-Oncology Research Group. One hundred and forty-eight
      cases of germ cell tumor were entered into this study between April, 1986 and
      August, 1995. They included 99 cases (66.9%) of seminoma and 49 cases (33.1%) of
      non-seminomatous germ cell tumor (NSGCT). The mean age of seminoma cases (39.7
      yrs) was higher than that (30.2 yrs) of NSGCT cases. One hundred and twenty-three
      cases were treated according to our protocol. In the treatment group, one patient
      with stage I seminoma died of other diseases and one patient each with stage II
      and stage III seminoma died of cancer. Three patients with stage III NSGCT died
      of cancer. The 5-year survival rate was 100% for stage I seminoma, and stage I
      and stage II NSGCT, 75.0% for stage II seminoma, 0% for stage III seminoma and
      66.7% for stage III NSGCT. These findings suggest that new treatment modalities
      should be introduced into our protocol in the future.

PMID- 9013231
TI  - [A case of papillary renal cell carcinoma with abnormal vascularity revealed by
      pharmacoangiography].
AB  - A 64-year-old man with a right renal mass was referred to our hospital for
      further examination. The tumor demonstrated no dye enhancement of the
      computerized tomography (CT) scan. The tumor appeared as a low signal intensity
      image on the T1 weighted magnetic resonance imaging (MRI) and as a high signal
      intensity image on the T2 weighted MRI. Angiography revealed as hypovascular
      mass, however, the vessels in the tumor appeared on pharmacoangiography due to
      the absence of vasconstrictive response. A right radical nephrectomy was thus
      performed. The tumor was mostly necrotic and had a thick capsule. The
      histopathological findings indicated the tumor to be papillary adenocarcinoma.

PMID- 9013232
TI  - [A case of CEA and CA19-9 producing recurrent transitional cell carcinoma in an
      Indiana pouch after total cystectomy].
AB  - A 73-year-old female with transitional cell carcinoma (TCC) of the bladder
      underwent total cystectomy and Indiana pouch replacement in April, 1992.
      Histological examination revealed grade 3 TCC. In February 1995, she complained
      of gross hematuria. Intravenous pyelography (IVP) revealed a right non-functional
      kidney and filling defect in the Indiana pouch. We suspected colon cancer in the
      Indiana pouch because the levels of serum carcino-embryonic antigen (CEA) and
      CA19-9 were elevated. Endoscopic biopsy of intrapouch tumor was done.
      Pathological examination revealed grade 2 TCC. In July 1995, right
      nephroureterectomy with resection of Indiana pouch was performed and the surgical
      specimen revealed renal pelvic and ureteral cancer, grade 2 TCC. The levels of
      serum CEA and CA19-9 returned to the normal range 21 days after the operation.
      CEA and CA19-9 histochemical stain of renal pelvic and ureteral cancer were
      positive. Also CEA-, CA19-9-positive cells were detected in the specimens of the
      bladder tumor from the total cystectomy performed in 1992. This rare case is
      discussed and the literature is reviewed.

PMID- 9013230
TI  - [Effects of Gosha-Jinki-Gan on the function of the urinary bladder in
      anesthetized dogs].
AB  - Gosha-Jinki-Gan is clinically used for the treatment of pollakiuria in patients
      with benign prostatic hyperplasia. The effect of Gosha-Jinki-Gan on the function
      of the urinary bladder in anesthetized dogs was examined. Gosha-Jinki-Gan (100
      mg/kg) inhibited the rhythmic bladder contractions (RBC). However, the frequency
      of RBC increased resembling the effect of atropine (0.1 mg/body), and the
      amplitude decreased. On the cystometrogram, Gosha-Jinki-Gan caused an increase in
      maximum vesical volume (not significant). These findings indicated that Gosha
      Jinki-Gan is a useful drug for the treatment of pollakiuria.

PMID- 9013234
TI  - [A case of postrenal acute renal failure in a neonate with bilateral ectopic
      ureters].
AB  - A male neonate was referred to our institute after the placement of right
      nephrostomy because he presented syndrome of acute renal failure and bilateral
      hydronephrosis. Voiding cystourethrography revealed bilateral vesicoureteral
      reflux (right.; grade I, left.; grade V), and renal scintigraphy revealed left
      hypodysplastic kidney. Endoscopy revealed bilateral ectopic ureters; posterior
      urethra on the right and bladder neck on the left. We performed bilateral
      ureterocystoneostomy with bilateral ureteral folding. Postoperative course was
      uneventful, and the serum creatinine improved to the level of 0.5 mg/dl 6 months
      after the intervention.

PMID- 9013233
TI  - [Ectopic ureter opening in the vestibulum without urinary incontinence: a case
      report].
AB  - A case of ectopic ureter without urinary incontinence despite its ureteral
      orifice in the vestibulum is reported. A 2-year-and-9-month-old female was
      referred to our hospital with the pain of external genitalia, pollakisuria and
      macroscopic hematuria. Examination revealed a complete double system of the left
      upper tract with vestibular opening from the upper moiety. She did not show any
      signs of ureteric incontinence after the establishment of voiding habits. Because
      radioisotope (RI) scintigram showed apparent uptake in the upper half of the left
      kidney we performed left ureterocystoneostomy with psoas hitch procedure. We
      postulate that the incontinence mechanism is maintained when the running course
      of the ectopic ureter is through some portion of the urethral sphincter
      musculature. This is the 10th case reported in Japan.

PMID- 9013235
TI  - Mainz pouch with appendix-umbilical stoma using catheterizable conduit elongated
      with continuous cecal segment: a case report.
AB  - The Mainz pouch with appendix-umbilical stoma is a very stable method for
      continent, self-catheterizable urinary reservoir in the presence of a healthy
      appendix. If the appendix is too short or an unexpected stenosis is seen at its
      distal portion, the elongation of the conduit using a part of the cecum and the
      implantation of the conduit to the pouch by the Mitrofanoff method can be a good
      alternative procedure. We herein report our experience in a 53-year-old male with
      high grade, invasive bladder tumor, who underwent cystourethrectomy and appendix
      Mainz pouch operation using the above technique.

PMID- 9013236
TI  - [Prostatic cancer with cystic formation: a case report].
AB  - A 60-year-old man was admitted to our hospital with the chief complaints of
      dysuria and sense of abdominal fullness. On digital rectal examination, an
      enlarged prostate with a smooth surface and elasticity was palpated. The
      concentration of prostate specific antigen (PSA) was elevated to 78 ng/ml. Pelvic
      computed tomographic (CT) scan and magnetic resonance imaging (MRI) revealed a
      large prostate, 8 cm in diameter, with a cystic mass, and extra-iliac lymph node
      swelling. On needle biopsy of the prostate and cyst, the histology was poorly
      differentiated adenocarcinoma, and the aspirate comprised bloody fluid with a
      negative test for cytology. He was diagnosed with prostatic cancer of T4N3M0.
      This is the 19th case of prostatic cancer with cystic formation reported in
      Japan.

PMID- 9013237
TI  - [A case of Fournier's gangrene with healing accelerated by argatroban].
AB  - A 58-year-old man was admitted to our hospital complaining of pain and marked
      swelling of scrotum and perineum. Physical and radiological examinations revealed
      gas-producing gangrenous changes involving the scrotum. Debridement was urgently
      carried out. Following the debridement under control of diabetes mellitus,
      antimicrobial agents and argatroban, a newly synthesized antithrombin medicine,
      were administered. Argatroban was used for the purpose of improving vascular
      insufficiency. Healthy granulation tissue was present five weeks later. Then
      surgical closure was carried out. Computed tomography was useful to make early
      diagnosis, and argatroban was thought to accelerate healing of the gangrene.

PMID- 9013239
TI  - Making surgical care better: hard work, small gains.

PMID- 9013238
TI  - [A case of Sparganosis mansoni with a painless mass in the inguinal region and
      the scrotum].
AB  - Sparganosis mansoni rarely occurs in the inguinal and perineal regions in Japan.
      A case of Sparganosis mansoni with a painless mass in the left inguinal region is
      presented. A 67-year-old male visited our hospital with a complaint of a painless
      mass in the left inguinal region in May, 1995, and another mass appeared in the
      scrotum two days after the first visit. Ultrasonography revealed a solid
      subcutaneous mass 2 cm in diameter. These masses were surgically excised by an
      inguinal approach and a parasite, 10 cm in length, was found in the mass. The
      parasite was diagnosed histologically as Sparganosis mansoni, which is a larva of
      the genus Diphyllobothrium.

PMID- 9013243
TI  - Correlation between frequency of tuberculosis and compliance with control
      strategies.
AB  - OBJECTIVE: To determine if compliance with annual tuberculosis skin testing
      correlated with the number of cases of tuberculosis seen in patients and
      healthcare workers. DESIGN: Survey using a written questionnaire. SETTING AND
      PARTICIPANTS: 159 Veterans' Administration facilities. RESULTS: Hospitals that
      reported that > 80% of their healthcare workers received annual skin tests saw
      12.7 patient cases per 10,000 admissions and 4.0 healthcare worker cases per
      10,000 personnel. Facilities in which < 20% of their healthcare workers were
      given annual skin tests saw 4.5 cases per 10,000 admissions and 1.6 cases in
      healthcare workers per 10,000 personnel (P < .001 for patients and P = .31 for
      healthcare workers). The ratio of the median number of patients placed in acid
      fast bacilli (AFB) isolation to the median number of patients with confirmed
      tuberculosis was 12. There was no correlation of this ratio with the number of
      cases of tuberculosis in patients or healthcare workers seen in each facility.
      CONCLUSION: Compliance with annual tuberculosis skin testing was related directly
      to the rate of tuberculosis seen in patients. More standardized policies for
      placing patients in AFB isolation are needed to control for potentially costly
      variation among facilities. These measures should have highest priority in the
      control of tuberculosis in the healthcare setting, before implementing still more
      expensive interventions.

PMID- 9013242
TI  - Does a cheaper mask save money? The cost of implementing a respiratory personal
      protective equipment program.
AB  - OBJECTIVE: To determine the annual cost of implementing and maintaining a
      respiratory personal protective equipment (PPE) program at an urban hospital.
      SETTING: St Clare's Hospital and Health Center, a 250-bed hospital in Manhattan
      that treats 60 to 100 cases of tuberculosis annually. METHODS: Review of
      Purchasing Department records for all masks acquired by the hospital from 1992 to
      1995, and an estimate of administrative time spent developing and implementing
      the guidelines recommended by various agencies during the study interval.
      RESULTS: Respiratory isolation was provided for 6,360 to 10,883 days annually
      during the 4-year interval. Yearly costs for the PPE program ranged from $86,560
      to $175,690. Of note, the daily cost for a respiratory isolation day decreased
      dramatically between 1994 and 1995 ($25/day to $13/day), when the high-efficiency
      particulate air-filter (HEPA) respirator was used by all staff. The decrease
      occurred because of lower administrative costs and a sharp decrease in the
      numbers of HEPA units purchased. Objective measures of worker compliance with
      HEPA respirators demonstrated the decrease was not due to less HEPA use but
      rather that employees were using each HEPA unit for several weeks, as
      recommended. CONCLUSION: We found a significant decrease in cost in the second
      year of our HEPA program due to increasing employee familiarity with the program.
      Newly approved, cheaper, but less durable, N-95 masks are unlikely to withstand
      multiple wearings and may be discarded after a few uses. Thus, cheaper masks may
      result in a more expensive PPE program.

PMID- 9013244
TI  - Use of electrophoretic karyotyping in the evaluation of Candida infections in a
      neonatal intensive-care unit.
AB  - OBJECTIVE: To evaluate a possible common-source outbreak of Candida infections in
      the neonatal intensive-care unit. Systemic Candida infections increased from 6 to
      11 cases (0.71 to 1.34 per 1,000 patient-days). In addition, Candida parapsilosis
      infections increased from 1 in 1992 to 10 in 1993. DESIGN AND SETTING: Tertiary
      care, teaching, pediatric institution with a 40-bed neonatal intensive-care unit
      (NICU). Clinical characteristics, associated conditions, and antimicrobial
      therapy were obtained from the medical records of all NICU patients with positive
      blood cultures for Candida during 1992 and 1993. Nineteen Candida isolates from
      15 infants were studied retrospectively using contour-clamped homogeneous
      electric-field (CHEF) electrophoresis. RESULTS: CHEF revealed eight karyotypes of
      C parapsilosis. Five isolates recovered from four patients shared one karyotype.
      The remaining isolates from seven infants all had distinctly different
      karyotypes. CONCLUSIONS: The evidence was insufficient to implicate a single
      source of infection, even though four patients in the same unit had identical
      strain types. However, identical strains of C parapsilosis were associated
      geographically, suggesting that nosocomial acquisition of C parapsilosis through
      indirect patient contact in the NICU was possible. The CHEF technique yields
      unique patterns that may be used to delineate clinical isolates and to study the
      molecular epidemiology of candidal infections.

PMID- 9013241
TI  - Nosocomial infections in surgical patients: comparison of two measures of
      intrinsic patient risk.
AB  - OBJECTIVE: To compare, in subjects undergoing general surgery, two measures of
      intrinsic patients risk for nosocomial infection: the Study on the Efficacy of
      Nosocomial Infection Control (SENIC) index and the National Nosocomial Infection
      Surveillance (NNIS) System index. DESIGN: Prospective cohort study, with follow
      up for 1 month after hospital discharge. SETTING: The general surgery service of
      a tertiary hospital. MAIN OUTCOME MEASURE: Surgical-site infection. PATIENTS:
      1,483 subjects aged 10 to 92 years. RESULTS: During follow-up, 155 patients
      developed nosocomial infection, yielding a cumulative incidence of 10.5%. The
      NNIS index showed a linear trend with both crude and adjusted (for SENIC index)
      rates of surgical-wound infection. The SENIC index did not exhibit any linear
      trend with adjusted (for NNIS index) rates of surgical-wound infection. To
      delineate whether the SENIC index added explanatory information to the NNIS index
      (or vice versa), we regressed each variable on the other. Logistic regression
      analyses confirmed the results of stratified analysis: residuals of the NNIS
      index added discriminating ability to the SENIC index, whereas residuals of the
      SENIC index did not improve the predictive power of the NNIS index. CONCLUSIONS:
      The NNIS index had a better ability than the SENIC index for discriminating and
      predicting risk of surgical-wound infection.

PMID- 9013240
TI  - Total cholesterol, HDL-cholesterol, and risk of nosocomial infection: a
      prospective study in surgical patients.
AB  - OBJECTIVE: To study the relationship between serum high-density lipoprotein
      cholesterol (HDL-C), total serum cholesterol, and nosocomial infection in
      patients undergoing general surgery. DESIGN: Prospective cohort study, with an
      extended follow-up to 1 month after hospital discharge. SETTING: The general
      surgery service of a tertiary hospital. MAIN OUTCOME MEASURE: Nosocomial
      infection, mainly surgical-site infection (SSI), urinary tract infection,
      respiratory tract infection (RTI), and bacteremia. PATIENTS: 1,267 surgery
      patients aged 10 to 92 years. RESULTS: 182 subjects acquired 194 nosocomial
      infections, a cumulative incidence of 14.5%; most (116, 62.3%) were postoperative
      wound infections. There was an increase in infection risk at low levels of HDL-C,
      and both low and high total cholesterol levels. After adjusting simultaneously
      for several confounders, including total cholesterol, low levels of HDL-C (< or =
      20 mg/dL) yielded an odds ratio (OR) of 2.2 (95% confidence interval [CI95], 0.6
      7.9) for SSI and an OR of 10.3 (CI95, 0.7-151.5) for RTI. Otherwise, no trend was
      observed between HDL-C levels and infection risk, and no increased risk of
      nosocomial infection was observed for HDL-C values in the range of 21 to 49
      mg/dL. Serum cholesterol showed a U-shaped relationship with nosocomial infection
      risk. Both low levels (below 102 mg/dL) and high levels (above 290 mg/dL) of
      total cholesterol were associated with a higher risk of SSI (mainly those caused
      by gram-negative bacteria) and RTI in comparison with the reference group (139
      261 mg/dL). CONCLUSIONS: Serum HDL-C and total cholesterol seem to be associated
      with the risk of nosocomial infection in surgical patients.

PMID- 9013247
TI  - The evolution of the surgical mask: filtering efficiency versus effectiveness.
AB  - When originally introduced for use at the turn of the century, the primary
      function of the surgical mask was to prevent the migration of microorganisms
      residing in the nose and mouth of members of the operating team to the open wound
      of the patient. As technology developed new materials and designs, their
      filtering efficiencies gradually improved. However, there is no standard test
      method for assessing that capability, and its influence on the rates of surgical
      wound infection has yet to be demonstrated. Quite to the contrary, both in-vitro
      and in-vivo studies indicate that a mask may not be universally necessary in
      today's surgical environment.

PMID- 9013246
TI  - DNA typing and control of methicillin-resistant Staphylococcus aureus at two
      affiliated hospitals.
AB  - OBJECTIVE: To describe control of endemic and outbreak-related methicillin
      resistant Staphylococcus aureus (MRSA) at two affiliated hospitals. DESIGN:
      Prospective surveillance of patients with MRSA. Disposable gloves were used by
      all staff having direct contact with the affected patient or his immediate
      environment, and patient isolates were typed by pulsed-field gel electrophoresis
      (PFGE) of genomic DNA. Surveillance and PFGE typing were used concurrently to
      identify possible nosocomial outbreaks, confirm or refute cross-infection, and
      support a need for additional outbreak control interventions. SETTING: A
      university hospital (Hospital A) and a university-affiliated public hospital
      (Hospital B). PARTICIPANTS: Patients with MRSA colonization or infection over an
      18-month interval (June 1993-November 1994). INTERVENTION: Proper handwashing and
      gloving practices were reemphasized with staff following confirmation of
      outbreaks. RESULTS: Hospital A had 60 community-acquired and 48 nosocomial cases
      of MRSA. Two small outbreaks (affecting a total of seven patients) and two pseudo
      outbreaks were identified. Hospital B had 36 community-acquired and 22 nosocomial
      cases of MRSA. Only one outbreak affecting five patients occurred. All outbreaks
      ended shortly after staff meetings that emphasized ongoing and extremely careful
      handwashing and gloving when caring for identified patients. The majority of
      nosocomial cases at both hospitals were not related epidemiologically or had
      isolates with unique PFGE types. Pseudo-outbreaks were confirmed by demonstrating
      that isolates from epidemiologically related cases (by time and clinical service
      or hospital unit) had different PFGE types. Hospital A cases had 39 different
      PFGE types, and Hospital B cases had 31 different PFGE types. CONCLUSION: MRSA in
      hospitals, including outbreaks identified by prospective surveillance and
      confirmed by PFGE typing, can be controlled by minimal special precautions and
      interventions. This is possible despite the continuous admission of patients with
      MRSA from the community. PFGE typing is useful to confirm outbreaks and pseudo
      outbreaks, demonstrate differences among epidemiologically unrelated isolates,
      and substantiate the efficacy of MRSA control programs within hospitals.

PMID- 9013249
TI  - Mathematical models in decision analysis.
AB  - Decision analysis offers powerful techniques to understand and evaluate uncertain
      clinical situations better. Decision analytic models are appearing with
      increasing frequency in health policy planning, clinical information and decision
      support computer systems, evaluations of clinical pathways, development of
      clinical practice or utilization review guidelines, and epidemiologic research.
      This article describes the structure, application, and limitations of the more
      popular decision analytic methods, including decision trees, Markov models, Monte
      Carlo simulation, survival and hazard functions, fuzzy logic, and sensitivity
      analysis. Understanding the nature of these methods will help readers to assess
      better the appropriateness of their use in published reports.

PMID- 9013248
TI  - Isolation.
AB  - Patients infected or colonized with certain microorganisms must be placed in
      isolation while hospitalized to prevent nosocomial transmission of these
      pathogens. Isolation systems enable healthcare workers to identify patients who
      need to be isolated and to institute the appropriate precautions. This article
      presents an overview of isolation precautions, emphasizing the latest guidelines
      from the Centers for Disease Control and Prevention.

PMID- 9013245
TI  - Implementation of consensus guidelines for the follow-up of positive blood
      cultures.
AB  - OBJECTIVE: Assess the effect and use of resources associated with implementation
      of a program for the systematic follow-up of positive blood cultures. DESIGN:
      Prospective epidemiologic study. SETTING: Tertiary-care military medical center.
      INTERVENTION: All positive blood cultures (BC) were reported via E-mail to an
      infectious disease specialist as soon as growth was noted. This individual
      reviewed all Gram stains, clinical data, and antibiotic information on these
      patients. RESULTS: From June 26, 1994, through January 25, 1995, there were 3,121
      BCs drawn, of which 199 (6.4%) were positive from 145 episodes. Sixty-three
      episodes involved probable contaminants, and 82 episodes were considered true
      bacteremias. Six patients with true bacteremia died, two were transferred, and
      three were discharged within 24 hours of drawing the positive BC. Of the
      remaining 71 true bacteremias, 9 patients were on inadequate empiric therapy, as
      judged by the final organism susceptibilities. Changes in empiric therapy were
      recommended for five of the nine episodes and were implemented by the primary
      physicians in each case. Each of the changes resulted in improved coverage (as
      judged by the final identification and susceptibilities). CONCLUSIONS: This
      program has improved the quality of care at Keesler Medical Center at the cost of
      one additional hour of consultant time per week.

PMID- 9013250
TI  - Regulation of the ecdysone receptor, USP, E75 and MHR3 mRNAs by 20
      hydroxyecdysone in the GV1 cell line of the tobacco hornworm, Manduca sexta.
AB  - The responsiveness of several nuclear transcription factor genes to 20
      hydroxyecdysone (20E) was characterized in an embryonic cell line, GV1, from
      Manduca sexta. The mRNA for the Manduca ecdysone receptor (MsEcR) was present in
      the GV1 cells and transiently increased 2.3-fold by 5 h after the addition of 2
      micrograms/ml (4 x 10(-6) M) 20-hydroxyecdysone (20E). In contrast, Manduca
      ultraspiracle (MsUSP) mRNA level in the GV1 cells decreased slowly to half of its
      initial level by 12 h when exposed to the same concentration of 20E. The mRNAs
      for two putative transcription factors, MsE75 and MHR3, were induced in the GV1
      cells by 20E, with that for E75 appearing within 1 h whereas that for MHR3 within
      2 h. The ED50S for induction of MsE75 and MHR3 gene expression in GV1 cells were
      1.2 x 10(-6) and 2.5 x 10(-6) M 20E, respectively.

PMID- 9013252
TI  - Analysis of eriophyid mite rDNA internal transcribed spacer sequences reveals
      variable simple sequence repeats.
AB  - Ribosomal DNA internal transcribed spacers of the eriophyid mites Cecidophyopsis
      ribis, C. selachodon, C. spicata, C. alpina, C. aurea, C. grossulariae and
      Phylocoptes gracillis were amplified using PCR, cloned and sequenced. Sequences
      for the ITS1 of Cecidophyopsids were 92-99% homologous. Cecidophyopsis inter
      specific differences were found in seventeen simple sequence repeats (vSSRs),
      fourteen point mutations and two indels. No intra-specific variation in vSSRs was
      detected. A hypothetical structure for ITS1 was obtained and vSSRs were mapped
      onto this. Changes in vSSRs were compensated for by changes in complementary
      vSSRs or through multiple point mutations. A comparison with vSSRs of other
      arthropods suggested that the levels of intra-specific variation in
      Cecidophyopsis mites was less than in organisms which do not use arrhentoky for
      male determination.

PMID- 9013255
TI  - Cloning and characterization of cDNAs preferentially expressed in the ovary of
      the mosquito, Anopheles gambiae.
AB  - We used differential screening to isolate from an ovarian cDNA library two
      expressed sequences that are enriched substantially in ovaries of blood-fed
      female Anopheles gambiae, as compared to female carcass and male mosquitoes. One
      of these clones encodes an isoform of histone H2B, whose transcript is
      polyadenylated at the 3' end. The other cDNA clone encodes a protein that is
      highly conserved in evolution and has been implicated in growth control although
      its function is still obscure. Both genes can be used to study gene activation
      during An. gambiae oogenesis.

PMID- 9013253
TI  - In vitro cultivation of Wolbachia pipientis in an Aedes albopictus cell line.
AB  - A continuous cell line, Aa23, was established from eggs of a strain of the Asian
      tiger mosquito, Aedes albopictus, naturally infected with the intracellular
      symbiont Wolbachia pipientis. The resulting cell line was shown to be
      persistently infected with the bacterial endosymbiont. Treatment with antibiotics
      cured the cells of the infection. In the course of establishing this cell line it
      was noticed that RFLPs in the PCR products of two Wolbachia genes from the
      parental mosquitoes were fixed in the infected cell line. This indicates that the
      mosquito host was naturally superinfected with different Wolbachia strains,
      whereas the infected cell line derived from these mosquitoes only contained one
      of the original Wolbachia strains. The development of an in vitro culture system
      for this fastidious microorganism should facilitate molecular analysis of the
      reproduction distorting phenotypes it induces in natural arthropod hosts.

PMID- 9013251
TI  - Mosquito hexamerins: characterization during larval development.
AB  - We report here the first examination of hexamerins expressed during mosquito
      larval development. Haemolymph proteins from fourth-instar larvae of six species
      representing the two major subfamilies of mosquitoes were characterized by
      immunoblotting using antisera to calliphorin, the major hexamerin of the blowfly.
      Calliphora vicina, or to LSP1 or LSP2, the two distinct hexamerins of Drosophila
      melanogaster. In each mosquito species the antisera demonstrated the presence of
      multiple abundant hexamerin polypeptides of 66-85 kDa in molecular weight.
      According to the subunit composition of native proteins, the larval hexamerins
      from both Aedes aegypti and Anopheles gambiae form heterohexamers. Furthermore,
      the two major Aedes hexamerin subunits (AaHex1 and AaHex2) are neither rich in
      aromatic amino acids nor methionine. cDNA clones encoding AaHex1 and AaHex2 were
      isolated and used to show that hexamerin mRNA is uniquely expressed in fourth
      instar larvae of both A. aegypti and A. gambiae and disappears rapidly at the
      onset of pupal development.

PMID- 9013254
TI  - Identification and mRNA developmental profiles of two ultraspiracle isoforms in
      the epidermis and wings of Manduca sexta.
AB  - cDNAs were isolated from Manduca sexta that encode two isoforms of an
      ultraspiracle (USP) homologue MsUSP-1 and MsUSP-2 with different N-terminal A/B
      regions. The MsUSP-1 cDNA predicts a protein with 97% and 45% amino acid
      identities in the DNA- and ligand-binding domains respectively to the Drosophila
      USP and 89% overall identity with Bombyx mori CF1 (an USP homologue). Northern
      blot hybridizations with probes specific to MsUSP-1 and MsUSP-2 showed
      transcripts of an approximately equal size (4.5 kb), but with diverse
      developmental profiles in Manduca epidermis during the two final larval instars
      and the onset of the adult moult. The MsUSP-1 mRNA was expressed during the
      intermoult periods, with higher levels around the time of the larval ecdyses and
      at the onset of wandering behaviour. In contrast, the MsUSP-2 mRNA was up
      regulated at times of high ecdysteroid titre during the larval moults, when the
      MsUSP-1 mRNA disappeared. Together, these conversely regulated isoform mRNAs
      contribute to the constitutive expression profile of total MsUSP mRNA.

PMID- 9013256
TI  - Juvenile hormone controls early trypsin gene transcription in the midgut of Aedes
      aegypti.
AB  - Early trypsin is a female-specific protease present in the Aedes aegypti midgut
      during the first few hours after ingestion of a blood meal. The enzymatic
      activity of early trypsin plays an essential role in the transcriptional
      activation of the late trypsin gene, which encodes the major midgut endoprotease
      involved in blood meal protein digestion. Transcription of the early trypsin gene
      is part of the normal post-emergence maturation of the midgut in the adult
      female. Abdominal ligation within 1 h of emergence completely prevented the
      transcription of the early trypsin gene. Topically applied JH III or methoprene
      induced transcription of the early trypsin gene in ligated abdomens to levels
      similar to those observed in non-ligated females. The induction of early trypsin
      transcription by JH is dose-dependent and 'head-independent', suggesting that
      factors coming from the neuro-secretory axis are not required.

PMID- 9013258
TI  - Phenobarbital induction of CYP6D1 is due to a trans acting factor on autosome 2
      in house flies, Musca domestica.
AB  - To improve our understanding of phenobarbital (PB) mediated induction of CYP6D1
      we examined the genetic linkage of PB induction using PB responsive (aabys) and
      non-responsive (LPR) strains of house flies. PB induction was linked to autosome
      2, indicating that CYP6D1 is trans regulated by this PB inducible element. Our
      results are discussed relative to a previous hypothesis that the same regulatory
      genes are responsible for both induction and monooxygenase-mediated insecticide
      resistance.

PMID- 9013257
TI  - Cloning and sequence of a gene for a homologue of the C subunit of the V-ATPase
      from the salivary gland of the tick Amblyomma americanum (L).
AB  - A 1084 base pair partial cDNA showing similarity to the C subunit of the vacuolar
      ATPase (V-ATPase) was isolated on a clone from a cDNA library made from salivary
      glands from 3-day-old feeding adult Amblyomma americanum (L.) female ticks. The
      5' end was completed using primer extension and the two pieces joined to form a
      complete cDNA of 1373 bp. This mRNA is expressed in embryos and the salivary
      glands of unfed adults and adult females at all stages of feeding. Specific
      inhibitors of the V-ATPase decrease the rate of dopamine-stimulated secretion of
      isolated salivary glands, but not as much as ouabain, an inhibitor of the Na+, K+
      ATPase, indicating that a V-ATPase may participate in the mechanism of salivary
      fluid secretion in A. americanum, but the volume of saliva secreted is more
      dependent on an active Na+, K+ ATPase.

PMID- 9013259
TI  - Rapid cloning of insect transposon insertion junctions using 'universal' PCR.
AB  - Very highly degenerate primers with short specific 3' anchor sequences and 5'
      adaptors were used in conjunction with nested specific primers to amplify large
      numbers of unknown insertion junctions of the insect retrotransposon Woot, using
      genomic DNA as template for the polymerase chain reaction (PCR). This technique,
      sometimes referred to as universal PCR, is a powerful method for molecular
      characterization of transposon insertions into genomes, and more generally for
      short-distance chromosome walking through unknown DNA. Twenty-four unique
      insertion junctions were cloned and sequenced from two strains of Tribolium
      castaneum and one strain of T. freemani. Inspection of these sequences revealed
      that integration of the Woot retrotransposon is cued by the insertion target
      motif, GTAC, in both species.

PMID- 9013260
TI  - Preferential codon usage and two types of repetitive motifs in the fibroin gene
      of the Chinese oak silkworm, Antheraea pernyi.
AB  - In this paper we describe the peculiar structures and preferential codon usage
      found in wild silkworm fibroin genes. We determined a 1350 bp nucleotide sequence
      from the Chinese oak silkworm, Antheraea pernyi. The deduced amino acid sequence
      was partitioned into thirteen polyalanine-containing repetitive motifs, which was
      one of the characteristics of Antheraea fibroins. Eleven of these arrays can be
      classified into two types of motifs depending on difference in amino acid
      sequences following polyalanine. Repetitive motifs structurally similar to those
      of A. pernyi were detected in a homologue of the Japanese oak silkworm, Antheraea
      yamamai. The most remarkable feature of this study was preferential codon usage,
      especially seen in alanine synonymous codons within both homologues of Antheraea:
      isocodon GCA most frequently occurred in alanine isocodons. In contrast, GCU
      isocodon was the most abundant in Bombyx mori fibroin heavy chain that lacks
      polyalanine arrays. This result strongly suggests different modes of selective
      constraint between the two types of fibroin gene. The similar finding that GCA
      isocodon was most frequent in two dragline silk sequences of the spider, Nephila
      clavipes, is consistent with our results because of the repetitive polyalanine
      containing arrays seen in spider dragline silk.

PMID- 9013262
TI  - How to do a simple epidemiological study. I. Planning.

PMID- 9013261
TI  - The nonvitellogenic female protein of Musca domestica is an adult-specific
      hexamerin.
AB  - During Musca domestica vitellogenesis a protein is preferentially synthesized by
      the female fat body and accumulates in the haemolymph but not in the ovaries.
      This protein, designated nonvitellogenic female protein (NVFP), was purified and
      shown to be a hexamer with an M(r) = 430 kDa, and subunits of M(r) = 70 kDa. The
      hexamer dissociates into subunits when the pH is elevated from 7.0 to 9.0. Two
      cDNA clones, F0 and F2, were isolated and analysed. The 2.2 kb F2 clone has an
      open reading frame that encodes a conceptual translation product that has
      similarity to the Drosophila melanogaster LSP-2 hexamerin. Recombinant protein
      from the F2-cDNA is recognized by a specific anti-NVFP serum. The temporal
      pattern of mRNA expression of the gene represented by the F2 clone follows that
      determined for the synthesis of NVFP. The data support the conclusion that NVFP
      is an hexamerin specific to the adult stage of Musca domestica.

PMID- 9013263
TI  - Oxy free radical system in heart failure and therapeutic role of oral vitamin E.
AB  - Twenty patients of heart failure and ten matched healthy controls were included
      in the trial. Out of these 20 patients of heart failure, 12 patients were also
      studied prospectively. Plasma levels of superoxide anion and malonyldialdehyde
      were increased while the levels of superoxide dismutase, catalase and glutathione
      reductase were decreased in patients of heart failure as compared to control
      subjects. The alteration in oxidative stress and antioxidant system did not
      correlate with the age and sex of patients or the etiology of heart failure. With
      the increasing severity of heart failure the malonyldialdehyde and superoxide
      anion increased significantly and catalase, glutathione reductase and superoxide
      dismutase levels decreased. The group of heart failure patients with ejection
      fraction < 40% (n = 7) exhibited significantly higher levels of malonyldialdehyde
      than those with an ejection fraction > 40% (n = 13). The superoxide anion and
      malonyldialdehyde levels were significantly higher in patients of heart failure
      in the pre-treatment state as compared to those in post-treatment state.
      Conversely catalase, glutathione reductase and superoxide dismutase were higher
      in the post-treatment period as compared to their values before treatment. The
      addition of vitamin E in doses of 400 mg once a day orally for 4 weeks
      significantly reduced the malonyldialdehyde and superoxide anion levels and
      produced an elevation of the antioxidant enzymes. Thus, there is an apparent
      normalisation of the indices of oxidative stress following treatment of heart
      failure and a markedly improved response on vitamin E supplementation which may
      be more beneficial.

PMID- 9013267
TI  - Relationships between electrocardiographic and echocardiographic findings in
      systemic sclerosis (scleroderma).
AB  - We assessed the prevalence of electrocardiographic abnormalities in patients with
      systemic sclerosis and evaluated their functional significance through a
      comparison with echocardiographic findings. Seventy-two patients with systemic
      sclerosis and 64 controls underwent resting electrocardiogram (ECG) and M-mode,
      two-dimensional, Doppler and color Doppler echocardiography. Electrocardiographic
      abnormalities were observed in 48.7% of patients. Conduction disturbances (27.7%)
      infarction pattern (13.8%), non-specific ST-T wave changes (13.8%) and right
      ventricular hypertrophy (11.1%) were the most frequent abnormalities. QTc
      interval was significantly longer in patients with systemic sclerosis than in
      controls. Significant differences between patients and controls were found in the
      prevalence of long QTc interval (p = 0.0016) infarction pattern (p = 0.0016),
      right ventricular hypertrophy (p = 0.007) and non-specific ST-T wave
      abnormalities (p = 0.0016). All patients with infarction pattern and 90% of
      patients with prolonged QTc interval had some echocardiographic abnormalities.
      Electrocardiographic signs of right ventricular hypertrophy were 16% sensitive
      and 93% specific for pulmonary hypertension; the sensitivity and specificity of
      the combination of right ventricular hypertrophy, right atrial enlargement and
      right bundle branch block were 35% and 90%, respectively. Standard ECG is useful
      to assess cardiac involvement in patients with systemic sclerosis. If infarction
      pattern, right ventricular hypertrophy or long QTc interval are present, a
      cardiac involvement is very likely.

PMID- 9013265
TI  - Plasma levels of atrial natriuretic peptide and of other vasoconstricting
      hormones in patients with chronic heart failure: relationship to exercise
      capacity.
AB  - We investigated the relationship between exercise capacity and the level of
      neurohormonal activation at rest and during exercise in patients with various
      degrees of severity of chronic heart failure. We performed exercise testing with
      measurements of peak oxygen consumption (pVo2) and blood sampling at rest and at
      peak exercise in eight patients with moderate heart failure (pVo2 = 17 +/- 0.4
      ml/kg/min) (mean +/- S.E.M.) and eight patients with severe CHF (pVo2 = 9 +/- 1
      ml/kg/min). None of the patients was taking angiotensin converting enzyme
      inhibitors or beta-blockers. Plasma levels of atrial natriuretic peptide, cGMP,
      arginine-vasopressin, renin, angiotensin II, epinephrine and norepinephrine
      increased significantly (P < 0.01), from rest to peak exercise, in all patients.
      Among all the studied neurohormonal factors, only atrial natriuretic peptide
      levels at rest as well as at peak exercise, in patients with severe heart failure
      were correlated significantly to pVo2 (r = -0.77, P = 0.04; r = -0.85, P = 0.01,
      respectively) and to exercise duration (r = -0.72, P = 0.05; r = -0.79; P = 0.03,
      respectively). The relationship between plasma levels of atrial natriuretic
      peptide and of cGMP was shifted downward in the more severe patients suggesting
      the loss of biological activity of atrial natriuretic peptide.

PMID- 9013266
TI  - Nifedipine gastrointestinal therapeutic system versus atenolol in stable angina
      pectoris. The Netherlands Working Group on Cardiovascular Research (WCN).
AB  - The gastrointestinal therapeutic system formulation of nifedipine enables a once
      daily dosing resulting in predictable, relatively constant plasma concentrations.
      To evaluate the efficacy and safety of this formulation and to compare this with
      the beta-blocker atenolol, we conducted a double-blind, randomised, multi-centre
      study in 129 male patients with documented exercise induced angina pectoris.
      After 4 weeks' treatment, nifedipine (60 mg), improved time to onset of 0.1 mV ST
      segment depression from 536 s by 72 +/- 117s, time to onset of pain from 619 s by
      56 +/- 120 s, and total exercise time from 685 s by 40 +/- 88 s. Atenolol 100 mg,
      had a comparable effect, time to onset of 0.1 mV ST-segment depression improved
      from 496 s by 53 +/- 129 s, time to onset of pain from 572 s by 57 +/- 118 s, and
      total exercise time from 653 s by 33 +/- 99 s. Between group analysis revealed no
      statistically significant differences for these exercise parameters. Atenolol,
      but not nifedipine, significantly reduced heart rate and systolic blood pressure
      at rest and during exercise (P < 0.001 between groups), indicating different
      modes of action of the drugs. With regard to safety, both drugs were generally
      well tolerated. There were significantly (P = 0.01) more vasodilation related
      side effects with nifedipine. These data demonstrate that gastrointestinal
      therapeutic system formulation of nifedipine and atenolol as once-daily
      monotherapy are equally effective and safe, but with different effects on
      exercise parameters.

PMID- 9013268
TI  - Lipoprotein analyses in patients with stable angina and acute coronary syndrome.
AB  - We have performed lipid analyses by using a table-top ultracentrifuge based on
      the Hatch and Lees' method in 77 subjects (60 men, 17 women: mean age, 63 years)
      to clarify lipoprotein disorders in coronary artery disease. Sixty-four subjects
      had coronary artery disease and 13 normal subjects were controls. They were
      divided into the groups with stable angina pectoris and with unstable angina
      pectoris or acute myocardial infarction (acute coronary syndromes). In patients
      with coronary artery disease, there were no significant differences from control
      in age, body mass index, total cholesterol, however, HDL cholesterol was
      significantly lower than those in the controls. LDL cholesterol:LDL apoB ratio,
      which is thought to reflect the size of LDL in coronary artery disease, was
      significantly smaller than that in the controls; mean values were 1.2 in coronary
      artery disease and 1.4 in controls. There were no significant differences in
      those lipoprotein disorders between the patients with stable angina and those
      with acute coronary syndromes. Though these lipoprotein abnormalities would not
      play a trigger role in acute coronary syndrome, they are characteristic of the
      lipid profile of patients with coronary artery disease.

PMID- 9013264
TI  - Interleukin-6 correlates with hemodynamic impairment during dobutamine
      administration in chronic heart failure.
AB  - Proinflammatory cytokines have been implicated in the pathophysiology of chronic
      heart failure. We determined mixed venous levels of interleukin-6 (IL6) in 18
      heart transplant candidates before, 1, 4, and 24 h after initiation of dobutamine
      infusion (3 micrograms/kg/min) during hemodynamic evaluation. During the first 4
      h of dobutamine, systemic vascular resistance decreased (1358 to 1024 dyn x s x
      cm-5, P = 0.01) while cardiac index (2.3 to 2.9 l/min/m2, P = 0.008) increased.
      Both returned to baseline after 24 h. IL6 was elevated at baseline compared to
      age-matched controls (1.5 (0/4.3) vs. 0 (0/0.5) P = 0.003). There was an increase
      in IL6 from 1.5 (0/4.3) to 3.6 (0.3/5.3) pg/ml after 24 h (P = 0.04). We found
      higher IL6 levels in the sicker half of patients as defined by pulmonary
      capillary wedge pressure > 24 mmHg (P = 0.005), mean pulmonary arterial pressure
      > or = 35 mmHg (P = 0.01), right atrial pressure > 13 mmHg (P = 0.02), and heart
      rate > or = 87/min (P = 0.02) as well as mean arterial pressure < 82 mmHg (P =
      0.005). In conclusion, in this pilot study IL6 correlates with the severity of
      chronic heart failure during low dose dobutamine infusion.

PMID- 9013270
TI  - Concurrent alpha 1 adrenergic blockade and angiotensin converting enzyme
      inhibition in the treatment of congestive heart failure.
AB  - We tested the hypothesis that concurrent inhibition of the renin angiotensin
      system by enalapril (5 mg) and the sympathetic nervous system by alpha 1
      adrenergic blockade (prazosin 1 mg) will be superior to enalapril alone in 17
      patients with heart failure on standard therapy, in a single blind, placebo
      controlled, randomized parallel group study for 4 weeks. Enalapril alone induced
      a significant increase in exercise time from 499 +/- 412 s to 707 +/- 608 s (P <
      0.05, ANOVA), but the increase induced by the enalapril + prazosin combination
      was significantly greater (P < 0.025, MANOVA) from 214 +/- 271 to 1007 +/- 784 s
      as was the increase in creatinine clearance (P < 0.05).

PMID- 9013269
TI  - Triglyceride expression.
AB  - Current epidemiologic reports claim an important role for triglycerides in
      coronary artery disease (CAD). By cross-sectional data analysis, the role of
      triglycerides was assessed in 1726 consecutive patients investigated for chest
      pain, 1119 with CAD and 607 with normal coronaries. Besides study of male and
      female patients as separate groups, the males were divided into age groups of
      below 40 years, 41 to 50 years, 51 to 60 years and over 61 years. The female
      patients were divided into those below 50 years and over 51 years because of
      smaller numbers. Using the mean value for cholesterol, triglyceride, HDL
      cholesterol, LDL cholesterol and body mass index for normals as the demarcation
      line, logistic regression analysis was carried out to study their association in
      the patients with CAD and normals. Results showed that while the odds ratio for
      total cholesterol were higher for the younger age groups, the odds ratio for
      triglycerides were consistently higher for the groups over 51 years both male and
      female. It is speculated that there may be a difference in the relative
      importance of lipid fractions with reference to age in the development of
      atherosclerotic plaque with cholesterol playing a more important role in younger
      people and triglycerides being equally or more important in older people, on the
      basis of metabolic handling of lipid fractions.

PMID- 9013271
TI  - Torsades de pointes following radiofrequency catheter His ablation.
AB  - A case of polymorphic ventricular tachycardia torsade de pointes type, appearing
      in a 70-year-old female following radiofrequency catheter His ablation, is
      presented. The substrate was slow rate with ventricular bigeminy and QT
      prolongation which appeared after ablation. The same phenomenon reappeared after
      permanent VVIR pacemaker implantation with a basal rate of 55 beats/min. One
      episode of polymorphic ventricular tachycardia deteriorated into ventricular
      fibrillation, requiring a 360-J DC shock. Raising the pacemaker rate to 80
      beats/min abolished the arrhythmias.

PMID- 9013272
TI  - Multiple coronary-pulmonary fistulae involving all three coronary arteries: a
      case report.
AB  - Coronary pulmonary fistulae are rare cardiac anomalies. We present the case of a
      46-year-old woman with multiple coronary-pulmonary fistulae involving all three
      coronary arteries. She presented with atypical chest pain and had no obstructive
      coronary lesion. SPECT thallium study demonstrated no perfusion defect. The
      fistulae were multiple but small with only a small left to right shunt (Qp:Qs =
      1.2). The patient has remained well without intervention.

PMID- 9013273
TI  - Correlation between herpes and Epstein-Barr viruses and acute myocardial
      infarction.

PMID- 9013275
TI  - CA 19-9 serum course and prognosis of pancreatic cancer.
AB  - CONCLUSION: CA 19-9 measurement is a simple test that can be used for diagnosis
      as well as for prediction of resection, survival rate after surgery, and
      recurrences. METHODS: Serum expression of the tumor marker CA 19-9 was studied in
      2119 patients. RESULTS: The discriminating capacity between benign and malignant
      disease was high for CA 19-9, especially in patients with pancreatic cancer (n =
      347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type
      positive, the sensitivity increased to 92%. CA 19-9 levels were significantly
      lower in patients with resectable tumors (n = 126) than in those with
      unresectable tumors (n = 221, p < 0.0001) (sensitivity 74 vs 90%). CA 19-9
      dropped sharply after resection, but normalized only in 29, 13, and 10% in
      patients with stage I, II, and III, respectively. In unresectable tumors no
      significant decrease of CA 19-9 after laparotomy or bypass operation was found.
      In patients of the same tumor stage, the median survival time in those whose CA
      19-9 levels returned to normal after resection was significantly longer than in
      those with postoperative CA 19-9 levels that decreased, but did not return to
      normal (in stage I, 33 vs 11.3 mo, in stage II, 41 vs 8.6 mo, and in stage III,
      28 vs 10.8 mo). In patients with recurrent disease, 88% had an obvious rise in CA
      19-9 levels.

PMID- 9013274
TI  - Catheter perforation of left ventricle in aortic stenosis [corrected].

PMID- 9013276
TI  - CT diagnosis of intraductal papillary neoplasm of the pancreas in comparison with
      histopathologic findings.
AB  - CONCLUSION: The existence of excrescent nodules in the cystic component of
      intraductal papillary neoplasms (IPN) on computed tomography (CT) is useful for
      differentiating between malignant and benign lesions. BACKGROUND: We sought to
      evaluate the ability of CT to differentiate malignant from benign lesions in IPN
      of the pancreas. METHODS: CT findings in 20 cases of IPN (11 benign and 9
      malignant lesions) were compared with histopathological findings from subsequent
      surgery. RESULTS: The size of the cystic portion on CT did not correlate with the
      malignant potential of the lesion. Seven (78%) of 9 malignant lesions had
      excrescent nodules on CT, whereas 1 (9%) of 11 benign lesions did.

PMID- 9013277
TI  - Correlation between pancreatic endocrine and exocrine function and
      characteristics of pancreatic endocrine function in patients with diabetes
      mellitus owing to chronic pancreatitis.
AB  - CONCLUSION: Pancreatic endocrine capacities are remarkably disturbed in patients
      with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing
      to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled
      that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in
      noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of
      acinar cell and ductal cell function closely correlate with endocrine function
      (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes).
      BACKGROUND: We sought to clarify the differences of pancreatic endocrine function
      between pancreatic diabetes and primary diabetes, and to verify the correlations
      between pancreatic exocrine and endocrine dysfunction in patients with chronic
      pancreatitis. METHODS: Urinary C-peptide (CPR) excretion and fasting plasma
      glucagon levels in patients with pancreatic diabetes owing to calcific
      pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were
      studied in comparison with those in patients with insulin-dependent diabetes
      mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and
      in healthy controls (11 cases). In addition, pancreatic exocrine function was
      investigated in patients with chronic pancreatitis (calcific and noncalcific) and
      in healthy controls. The correlation between pancreatic exocrine and endocrine
      function was studied. RESULTS: The urinary CPR excretion in controls was 94.9 +/-
      20.5 micrograms/d. The urinary CPR excretion in calcific pancreatitis was 12.8 +/
      7.4 micrograms/d and it resembled that in IDDM (9.4 +/- 5.8 micrograms/d). The
      urinary CPR excretion in noncalcific pancreatitis was 41.5 +/- 30.1 micrograms/d,
      being similar to that in NIDDM (49.3 +/- 21.0 micrograms/d). The plasma glucagon
      level in calcific pancreatitis was 64.1 +/- 15.9 rho g/mL, which was
      significantly lower than the values in IDDM (111.2 +/- 50.2 rho g/mL) and NIDDM
      (96.7 +/- 21.9 rho g/mL). The plasma glucagon level in calcific and noncalcific
      pancreratitis (88.4 +/- 29.6 rho g/mL) were significantly lower than that in
      controls (129.8 +/- 21.6 rho g/mL). The residual capacities of acinar cells and
      ductal cells were strongly correlated with urinary CPR excretion and plasma
      glucagon concentration.

PMID- 9013281
TI  - The soluble interleukin-2 receptor, peripheral blood, and reticulocyte fractions
      in acute pancreatitis.
AB  - CONCLUSION: In acute pancreatitis (AP), the peripheral blood analysis, including
      reticulocytes (RC) and RC fractions, and its relationship to the changes of the
      levels of the soluble interleukin 2 receptor (sIL-2R) can provide useful
      information about the involvement of the immunoinflammatory system in AP and can
      indicate the severity of the disease. BACKGROUND: In the disease clinical
      assessment, we correlated the sIL-2R serum levels to the peripheral blood
      components (including RC and RC fractions) to serum albumin and C-reactive
      protein (CRP) during AP. METHODS: In 21 patients with AP, sIL-2R, the total and
      differential white blood cell (WBC) counts, red blood cell (RBC) counts, RC, RC
      fractions, hemoglobin (Hb), hematocrit (Ht), platelets (PLT), albumin, and CRP
      were evaluated from the onset to the sixth day of illness. RESULTS: sIL-2R
      increased in all the patients. The increase was directly related to eosinophils,
      monocytes, and to middle-aged (MFR) RC, and inversely related to neutrophils and
      the old (LFR) RC. MFR-RC were directly related to the total WBC count,
      eosinophils, and basophils, and inversely related to Hb and albumin. LFR-RC
      behaved in the opposite manner. CRP increased in 16 patients; this rise was
      directly related to WBC, RC, and MFR-RC, and inversely related to Hb, LFR-RC, and
      albumin. sIL-2R and CRP values were not statistically interrelated, but when the
      CRP levels were higher, the increase in sIL-2R was greater and more sustained.

PMID- 9013285
TI  - Quantitative determination of amphetamine and alpha-phenylethylamine enantiomers
      in judicial samples using capillary gas chromatography.
AB  - alpha-Phenylethylamine was recently reported by us in various samples seized from
      the illicit drug circuit. At first, alpha-phenylethylamine was identified in
      powders that generally contained amphetamine and caffeine. Then, a couple, who
      were known drug users, was found dead in their apartment. Urine samples from both
      victims contained large amounts of amphetamine and alpha-phenylethylamine. All of
      the positive samples were re-examined with gas chromatography to determine the
      chirality of the detected drug or drugs. The homochiral derivatizing reagent N
      trifluoroacetyl-L-prolyl chloride was used to convert the drug enantiomers into
      their corresponding diastereomeric derivatives. These derivatives were separated
      on an achiral stationary phase and detected using either flame ionization
      detection (FID) or on-line Fourier-transform infrared spectrometry (FTIR) for
      quantitative or qualitative purposes, respectively. Excellent separation was
      realized between all diastereomeric derivatives, and interference of excess,
      nonvolatile derivatizing reagent was reduced to a minimum. All powder samples
      consisted of racemic mixtures for alpha-phenylethylamine and for amphetamine. The
      urine samples also contained both enantiomers of alpha-phenyl ethylamine and
      amphetamine, albeit in varying proportions. These findings again substantiate the
      synthetic origin of alpha-phenylethylamine, attributing its presence in the urine
      of both victims to intentional or accidental intake. The disproportionate
      isomeric composition found in the urine samples confirms previous reports of a
      stereoselective metabolism for amphetamine enantiomers and suggests a similar
      pharmacokinetic profile for alpha-phenylethylamine.

PMID- 9013283
TI  - Bronchobiliary fistula. A rare complication of chronic pancreatitis.
AB  - CONCLUSIONS: Bronchobiliary fistula is an in frequent manifestation of common
      bile duct obstruction. The slowly progressive narrowing of the common duct by the
      fibrosis of chronic pancreatitis is an even more rare mechanism of such fistula
      formation with only two cases having been reported previously. A third case of
      bronchobiliary fistula caused by chronic pancreatitis is presented and its
      successful management is discussed. BACKGROUND: A 54-yr-old male with known
      chronic pancreatitis presented with a cough productive of copious amounts of bile
      and with pulmonary infiltrates. METHODS: Diagnosis of bronchobiliary fistula was
      made based on HIDA scan and confirmed by operative cholangiogram. RESULTS:
      Successful correction of this fistula was accomplished by operative closure of
      the fistulous tract and diversion of the narrowed bile duct by hepaticojejunal
      bypass.

PMID- 9013280
TI  - Pancreatic exocrine function during acute exacerbation in WBN/Kob rats with
      spontaneous chronic pancreatitis.
AB  - CONCLUSION: Pancreatic exocrine hypofunction is markedly deteriorated during
      acute exacerbation in a rat model with chronic pancreatitis. BACKGROUND: Little
      is known about pancreatic exocrine function during acute exacerbation in patients
      with chronic pancreatitis. We investigated changes in pancreatic exocrine
      function after inducing acute pancreatitis in an animal model of spontaneous
      chronic pancreatitis. METHODS: WBN/Kob rats with chronic pancreatitis
      sequentially underwent pancreatic exocrine function test 1-6 d after surgical
      preparation with external pancreatic fistula. We induced acute pancreatitis in
      another WBN/Kob rats by i.v. administration of cerulein at a rate of 10
      micrograms/kg/h for 4 h 4 d after surgical preparation. Pancreatic exocrine
      function test was undertaken in a conscious state 1 d before and after cerulein
      administration. RESULTS: In WBN/Kob rats not given cerulein, pancreatic exocrine
      function remained almost constant at 3-6 d after surgery. Marked hyperamylasemia
      developed immediately after cerulein administration. After its administration,
      the pancreas microscopically showed prominent interstitial edema and
      intracellular vacuolization of acinar cells in addition to the finding of pre
      existing chronic pancreatitis. Basal and cholecystokinin-stimulated flow rate,
      bicarbonate output, and protein output, which were substantially impaired 1 d
      before cerulein administration, were further reduced 1 d after its
      administration.

PMID- 9013284
TI  - Relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin,
      quinidine, and theophylline to human tissues in vitro.
AB  - The relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin,
      quinidine, and theophylline to human tissues in vitro was studied using
      equilibrium dialysis. Pooled human serum plus homogenates of brain, heart, liver,
      and placenta were incubated at 4 degrees C with each drug at concentrations of 5
      and 10 mmol/L. The percent binding of each drug to each tissue was calculated.
      Binding of 5% or less was considered to be negligible. By drug, the following
      relative binding orders were observed for those tissues demonstrating binding:
      acetaminophen (heart > brain, serum); lidocaine (no appreciable binding
      observed); phenobarbital (serum only); phenytoin (heart and liver equally; serum
      not studied); quinidine (serum > liver > brain, placenta); and theophylline
      (serum > liver). By matrix, serum bound all drugs studied except for lidocaine.
      Liver bound only phenytoin, quinidine, and theophylline; heart bound only
      acetaminophen and phenytoin; brain bound only acetaminophen and quinidine; and
      placenta bound only quinidine.

PMID- 9013279
TI  - In vitro chemosensitivity of human pancreatic cancer cell lines.
AB  - CONCLUSION: These results show that eight pancreatic cancer cell lines are
      broadly sensitive to CDDP, and that chemotherapy for pancreatic cancer may
      improve the prognosis by more effective drug delivery to cancer cells.
      BACKGROUND: Chemotherapy for pancreatic cancer does not satisfactorily improve
      prognosis. The efficacy of chemotherapy depends on choosing sensitive anticancer
      drugs. METHODS: The in vitro chemosensitivity of eight human pancreatic cancer
      cell lines was investigated. Growth inhibition was measured by 3H-thymidine
      incorporation assays for doxorubicin hydrochloride (ADM), mitomycin C (MMC),
      cisplatin (CDDP), and etoposide (VP-16), and by Alamar Blue assay for (AB assay)
      5-fluorouracil (5-FU). The cells were exposed to ADM, MMC, CDDP, and VP-16 for 2
      h, and 5-FU for 72 h. From the dose-response curves, the 50% growth inhibition
      (IC50) level for each drug was estimated. RESULTS: The IC50 after 2 h of exposure
      of each of the eight kinds of cell lines to each anticancer drug ranged from 0.12
      8.2 micrograms/mL for ADM, 0.066-25 micrograms/mL for MMC, 0.57-7 micrograms/mL
      for CDDP, 0.68-300 micrograms/mL for VP-16. IC50 after 72 h of exposure to 5-FU
      ranged from 1.8-23 micrograms/mL.

PMID- 9013282
TI  - The cholecystokinin receptor antagonist L-364,718 reduces taurocholate-induced
      pancreatitis in rats.
AB  - CONCLUSION: Our results suggest that the cholecystokinin (CCK) receptor
      antagonist L-364,718 has a protective effect on taurocholate-induced
      pancreatitis, and thus, it is inferred that CCK may have a significant
      pathophysiological role in the early phase of pancreatitis. BACKGROUND:
      Conflicting results have been obtained from studies designed to determine the
      role of CCK in the initial stages of pancreatitis. METHODS: We evaluated the
      protective effect of the CCK receptor antagonist L-364,718 (devazepide) and of
      the trypsin inhibitor camostat, on taurocholate-induced pancreatitis in rats. L
      364,718 (1 mg/kg) or camostat (200 mg/kg) was administered intragastrically 30
      min before the induction of pancreatitis. RESULTS: Infusion of sodium
      taurocholate (50 mg/kg) into the pancreaticobiliary duct caused severe
      pancreatitis with marked hyperamylasemia and reduction of tissue enzyme content
      at 12 h postinfusion. Pretreatment with L-364,718, but not with camostat, caused
      significant improvement in signs of experimental pancreatitis based on tissue
      enzyme content and morphology. Compared with untreated pancreatitis, there was
      relatively well-preserved lobular architecture, less edema, less infiltration of
      inflammatory cells, and more zymogen granules after L-364,718 pretreatment.
      Moreover, the reduction of enzyme content owing to pancreatitis was ameliorated
      by L-364,718 pretreatment.

PMID- 9013278
TI  - Role of hypertriglyceridemia in the pathogenesis of experimental acute
      pancreatitis in rats.
AB  - CONCLUSION: The pancreatic damage initiated via different pathogenetic pathways
      can be increased by triglycerides. Thus, triglycerides seem to play an important
      role in the pathogenesis of acute pancreatitis. BACKGROUND: Lipolytic enzymes and
      their substrates may play a role in the pathogenesis of acute necrotizing
      pancreatitis. We investigated, therefore, whether triglycerides alter the course
      of acute pancreatitis in three experimental models of rats. METHODS: 1. Edematous
      acute pancreatitis induced by repeated sc injections of cerulein; 2. Necrotizing
      acute pancreatitis by retrograde duct injection of sodium taurocholate; and 3.
      Pancreatic edema by ligation of: a. The bile duct at the liver hilus; b. The
      common bile/pancreatic duct close to the duodenal wall; or c. A combination of a.
      and b. Six hours later, rats were sacrificed and the isolated perfused pancreas
      prepared. The pancreases were perfused with either HEPES/Ringer/HAES alone or in
      combination with various concentrations of triglycerides (1-5% wt/vol). The
      activities of lipase and amylase in the portal venous effluents were regarded as
      a marker of pancreatic injury. In addition, the pancreases were evaluated by
      light microscopy. RESULTS: In both cerulein and taurocholate acute pancreatitis,
      amylase/lipase activities were significantly higher compared to controls during
      45 min of perfusion. In both models, addition of triglycerides caused a dose
      dependent marked elevation of enzymes. Ligation (a) did not cause any rise in
      enzymes in the venous effluent; triglycerides had no effect. Ligation (b) or (c)
      caused a significant increase of pancreatic enzymes, which was further increased
      by triglycerides. Histology showed various degrees of severity of tissue damage
      depending on the model used. The additional damaging effect of a 45-min perfusion
      with triglycerides, however, could not be detected by histology.

PMID- 9013287
TI  - Reduction in extraction efficiency of charged particles from the ion source as
      the cause of matrix effects in the GC-MS analysis of drugs.
AB  - Previous studies have shown that the ion response of a compound can be suppressed
      by the presence of a large amount of a coeluting substance in a gas
      chromatographic-mass spectrometric (GC-MS) system. In the present study, the
      change in the ion current of a constant amount of diazepam-d5 in the presence of
      a 100-fold amount of diazepam was used to monitor this condition in the Hewlett
      Packard mass selective detector (MSD). It was observed that a reduced recovery of
      ions occurred when the potentials of the MSD source elements were established by
      the autotune algorithm. Increasing the ion focus or the entrance lens potentials
      or both increased the recovery of the ion current of diazepam-d5 in the presence
      of large amounts of diazepam. The data suggested that the decreased recovery of
      ion current observed when the autotune source parameters were used was due to
      insufficient energy on the focusing lenses to extract a constant fraction of the
      ions from the source when a high concentration of molecules was present.

PMID- 9013289
TI  - Improved CEDIA benzodiazepine assay eliminates sertraline crossreactivity.
AB  - Initial experiments demonstrated that the original CEDIA (cloned enzyme donor
      immunoassay) benzodiazepine assay crossreacted with setraline and sertraline
      metabolites. In response to this phenomenon, Boehringer Mannheim Corporation
      developed an improved CEDIA benzodiazepine assay in order to eliminate sertraline
      crossreactivity. The improved CEDIA assay was evaluated against the original
      CEDIA product, EMIT II (enzyme multiplied immunoassay technique) benzodiazepine
      assay, and electron capture negative chemical ionization (ECNCI) gas
      chromatography-mass spectrometry (GC-MS). Five hundred and thirty-one urine drug
      screens were tested by the immunoassays. Sensitivity and specificity of these
      immunoassays for the 5-aryl-7-chloro-1,4-benzodiazepine compounds were 92 and
      98%, respectively, for the improved CEDIA assay; 92 and 93%, respectively, for
      the current CEDIA assay; and 87 and 98%, respectively, for EMIT II. The improved
      CEDIA assay performed almost identically to the EMIT II assay, both of which had
      a significant advantage over the original CEDIA product, which was subject to
      crossreactivity because of sertraline metabolites. The alpha-hydroxy ketone
      metabolites of sertraline are identified in human urine specimens for the first
      time using ECNCI GC-MS.

PMID- 9013288
TI  - Lack of predictable site-dependent differences and time-dependent changes in
      postmortem concentrations of cocaine, benzoylecgonine, and cocaethylene in
      humans.
AB  - This study evaluated the stability of cocaine, benzoylecgonine, and cocaethylene
      in postmortem fluids in cases of cocaine-related death. Femoral and ventricular
      blood and cisternal cerebrospinal fluid were collected soon after death and again
      at the time of autopsy. In addition, iliac blood was collected at autopsy. There
      were no consistent patterns of site-specific differences for any of the analytes,
      and the central compartment showed both higher and lower concentrations than the
      peripheral. There was no consistent pattern of direction or magnitude of change
      in the concentrations with respect to time for any of the analytes. This is
      consistent with anecdotal reports from other workers and is believed to be a
      result of competing processes of tissue release and chemical and enzymatic
      degradation of the analytes. Postmortem cocaine and metabolite concentrations in
      blood are not necessarily reflective of the perimortem concentrations and should
      not be the primary consideration in determining the cause of death in suspected
      cocaine-related deaths.

PMID- 9013291
TI  - Cocaine- and cocaethylene-creatinine clearance ratios in humans.
AB  - Cocaine (COC)- and cocaethylene (CE)-creatinine clearance ratios (CCR) were
      determined in five patients. In each case, COC:CCR greatly exceeded CE:CCR, and
      in four patients the data suggested renal tubular secretion of COC. For all
      patients, some renal tubular reabsorption of CE was apparent. These findings may
      be due, at least in part, to the greater hydrophobicity of CE relative to COC and
      to the lower pKb of CE (8.23) than that of COC (8.60). The pKb of CE was
      determined by titrimetry and is reported here for the first time. These data may
      be useful in investigating the pharmacokinetic profiles of COC and CE in humans
      and may also help to explain the longer plasma half-life of CE relative to that
      of COC.

PMID- 9013292
TI  - Ochratoxin A content of human sera determined by a sensitive ELISA.
AB  - A sensitive, monoclonal antibody-based ELISA test was developed and used for
      quantitative determination of ochratoxin A (OA) in human sera. The measuring
      range of this test (without sample dilution) was 0.2-2.0 ng/mL, and the detection
      limit was 0.2 ng/mL. The OA concentrations of 355 sera samples varied from < 0.2
      to 10 ng/mL OA, but 75% of the samples contained 0.2-1.0 ng/mL. This amount
      reflects a tolerable daily intake (TDI) value of toxin. However, in some cases
      (6.8%), more than 1.0 ng/mL OA was measured, which is probably a result of
      elevated intake of OA, which may even exceed the "virtually safe dose". Our data
      indicate that, like in many other countries, OA is present in food or feed
      products available in Hungary, and in order to save the health of consumers,
      their regular control is desirable.

PMID- 9013290
TI  - A simple and sensitive quantitation of N,N-dimethyltryptamine by gas
      chromatography with surface ionization detection.
AB  - A simple and sensitive method for determination of N,N-dimethyltryptamine (DMT)
      by gas chromatography (GC) with surface ionization detection (SID) is presented.
      Whole blood or urine, containing DMT and gramine (internal standard), was
      subjected to solid-phase extraction with a Sep-Pak C18 cartridge before analysis
      by GC-SID. The calibration curve was linear in the DMT range of 1.25-20 ng/mL
      blood or urine. The detection limit of DMT was about 0.5 ng/mL (10 pg on-column).
      The recovery of both DMT and gramine spiked in biological fluids was above 86%.

PMID- 9013286
TI  - A practical approach to determination of laboratory GC-MS limits of detection.
AB  - Determination of limit of detection (LOD) values in a forensic laboratory serves
      a fundamental forensic requirement for assay performance. In addition to
      demonstrating assay capability, LOD values can also be used to fulfill
      certification requirements of a high-volume forensic drug laboratory. The LOD was
      defined as the lowest concentration of drug that the laboratory can detect in a
      specimen with forensic certainty at a minimum of 85% of the time. Overall batch
      acceptance criteria included acceptable quantitation of control materials (within
      20% of target), acceptable chromatography (symmetry, peak integration, peak
      shape, peak, and baseline resolution), retention time within +/-1% of the
      extracted standard, and mass ion ratios within +/-20% of the extracted standard
      mass ion ratios. Individual specimen acceptance criteria were the same as the
      batch acceptance criteria excluding the quantitation requirement. Data were
      collected from all instruments on different runs. A minimum of ten data points
      was required for each certified instrument, and a minimum of 85% of data points
      was acceptable. Quantitation within +/-20% of the LOD concentration was not
      required, but acceptable mass ratios were required. Data points with poor
      chromatography (internal standard failed mass ratios; interference of the
      baseline, for example, shoulders; asymmetry; and baseline resolution) was omitted
      from the acceptable rate calculation. Data points with good chromatography with
      failed mass ion ratios were included in the acceptable rate calculation. With
      these criteria, we established the following LODs: 11-nor-delta 9
      tetrahydrocannabinol-9-carboxylic acid, 2 ng/mL; benzoylecgonine, 5 ng/mL;
      phencyclidine, 2.5 ng/mL; amphetamine, 150 ng/mL; methamphetamine, 100 ng/mL;
      codeine, 500 ng/mL; and morphine, 1000 ng/mL.

PMID- 9013293
TI  - Comparison of RapiTest with Emit d.a.u. and GC-MS for the analysis of drugs in
      urine.
AB  - Results obtained with RapiTest THC (One Step delta 9-Tetrahydrocannabinol Test),
      RapiTest MOP (One Step Morphine Test), RapiTest MET (One Step Methamphetamine
      Test), and RapiTest COC (One Step Cocaine Test) were compared with the results
      obtained with Emit d.a.u. and with gas chromatographic-mass spectrometric (GC-MS)
      methods. In all, 81 urine samples taken from specimens submitted for routine
      analysis in the Laboratory of Pharmacology and Toxicology were analyzed. Samples
      were screened with Emit, reanalyzed by RapiTests, and quantitated using GC-MS
      methods. Both positive and negative urine samples were tested. The results
      obtained with RapiTests correlated well with the Emit d.a.u. and GC-MS data when
      operating above the cutoff concentrations specified for these methods. RapiTest
      MOP was found to have crossreactivity with codeine and ethylmorphine, and
      RapiTest MET crossreacted with amphetamine.

PMID- 9013294
TI  - Simple extractive derivatization of methamphetamine and its metabolites in
      biological materials with Extrelut columns for their GC-MS determination.
AB  - A simple, extractive heptafluoro-n-butyrylation with Extrelut columns was devised
      to simultaneously measure methamphetamine (MAMP), amphetamine (AMP), 4
      hydroxymethamphetamine (HMAMP), and 4-hydroxyamphetamine (HAMP) in biological
      materials by gas chromatography-mass spectrometry (GC-MS) using 4
      methoxymethamphetamine-d5 as the internal standard. Human urine, human whole
      blood, and porcine skeletal muscle spiked with the stimulant standards were used
      for evaluating the method. After deproteinization and adjustment of the pH to
      12.6, the sample was applied to an Extrelut column. Using the present method,
      AMP, MAMP, and HMAMP could be determined in an actual forensic case study.

PMID- 9013295
TI  - Determination of phenylisothiocyanate derivatives of amphetamine and its
      analogues in biological fluids by HPLC-APCI-MS or DAD.
AB  - Amphetamine (A), methamphetamine (MA), methylene dioxyamphetamine (MDA),
      methylenedioxyethylamphelamine (MDE), and methylenedioxymethamphetamine (MDMA),
      as well as eight other sympathomimetic amines (benzyl-1-phenylethylamine,
      ephedrine, fenfluramine, norfenfluramine, phentermine, phenylethylamine,
      phenylpropanolamine, and propylhexedrine), were extracted from serum or urine
      with ether, derivatized with phenylisothiocyanate, and subjected to high
      performance liquid chromatographic (HPLC) examination in isocratic mode. Two
      detection arts were applied: atmospheric pressure chemical ionization (APCI) mass
      spectrometry (MS) and UV-spectrometry as diode array detection (DAD) or single
      wavelength at 250 nm. The derivatives were well-separated and showed good
      chromatographic behavior. Full-scan mass spectra of drugs examined by means of
      APCI with collision induced dissociation (APCID) contained protonated molecular
      ions (M+H)+ and fragments typical for particular drugs. APCID-liquid
      chromatography-mass spectrometry (LC-MS) appeared very selective for
      differentiation of all drugs involved. The quantitation with APCID was performed
      using selected ion monitoring (SIM) of (M+H)+ ions and selected fragments of
      drugs involved and their deuterated analogues. The limits of detection ranged
      from 0.001 mg/L (MA, MDMA, and MDE) to 0.005 mg/L (A and MDA). In HPLC-DAD, the
      spectra of MDMA and MDE were practically identical with maxima of 236-240 nm.
      Other amphetamines showed slightly different spectra with maxima of 245-250 nm.
      The limits of detection in UV detection amounted to 0.01-0.03 mg/L (single
      wavelength detector at 250 nm) or 0.05-0.1 mg/L (DAD).

PMID- 9013298
TI  - Enhanced detection of benzodiazepines by immunoassay.

PMID- 9013297
TI  - Potential for overestimation of clozapine concentrations.

PMID- 9013299
TI  - The significance of high follicular-phase luteinizing hormone levels in the
      treatment of women with polycystic ovarian syndrome by in vitro fertilization.

PMID- 9013296
TI  - Colchicine poisoning: report of a fatal case and presentation of an HPLC
      procedure for body fluid and tissue analyses.
AB  - A case involving a suicidal overdose resulting from the ingestion of colchicine
      tablets is presented. The drug was quantitated using liquid chromatography. The
      femoral blood level was 62 ng/mL, and the maximum concentration found in bile was
      2921 ng/mL. Therefore, bile appears to be the sample of choice for toxicological
      analysis when a poisoning case involving colchicine is suspected.

PMID- 9013300
TI  - Clinical utility of adjuvant growth hormone in the treatment of patients with
      polycystic ovaries undergoing in vitro fertilization.

PMID- 9013301
TI  - In vitro fertilization treatment in patients with polycystic ovaries.

PMID- 9013302
TI  - Treatment of polycystic ovary patients undergoing IVF.

PMID- 9013305
TI  - A case of a neurological complication after transvaginal oocyte retrieval.
AB  - A patient is described who developed neurological signs of the left leg following
      transvaginal ultrasound-guided puncture. A hypodense lesion of the obturator
      space above the lumbosacral plexus was seen on ultrasound which could explain her
      signs, due to compression by a hematoma. She recovered completely.

PMID- 9013303
TI  - The treatment of patients with polycystic ovaries undergoing IVF.

PMID- 9013307
TI  - In vitro fertilization programmed for weekday-only oocyte harvest: analysis of
      outcome based on actual retrieval day.
AB  - OBJECTIVE: Our aim was to assess the effect of the day of ovum retrieval on
      outcome in an IVF program scheduled for weekday-only ovum retrievals. DESIGN:
      This was a retrospective study of patients who underwent transvaginal ultrasound
      guided ovum retrieval (TVUS-OR) in an IVF program from August 10, 1992, to April
      30, 1993. SETTING: A university-based tertiary referral hospital center was the
      setting. PARTICIPANTS AND METHODS: All patients (n = 501) who underwent TVUS-OR
      were divided into three groups: (1) patients who underwent TVUS-OR on Monday; (2)
      patients who underwent retrieval on Tuesday, Wednesday, or Thursday; and (3)
      patients who underwent retrieval on Friday. All patients were induced by the same
      controlled ovarian hyperstimulation protocol, which consisted of a GnRH analogue
      "flare-up" followed by parenteral menotropins, after a scheduled oral
      contraceptive-induced menses. Patients and cycle characteristics in the three
      groups were compared and clinical outcome was evaluated. RESULTS: The similarity
      of patients and cycle characteristics confirmed the uniformity of the three
      groups. No difference was found in any of the clinical outcomes. However, in the
      first half of the program, we revealed a trend in which patients at high risk for
      ovarian hyperstimulation syndrome, requiring freezing all embryos and not
      allowing transfer during the treatment cycle, occurred more commonly in women
      whose retrieval occurred on Monday. This trend disappeared in the second half of
      the analysis. CONCLUSIONS: In an in vitro fertilization program in which ovum
      retrievals occurred only on weekdays, no significant difference in outcome was
      found in patients undergoing ovum retrieval on Monday or Friday versus midweek.
      In addition to significant savings by eliminating weekend retrievals, IVF outcome
      is not compromised.

PMID- 9013308
TI  - The role of uterine straightening by passive bladder distension before embryo
      transfer in IVF cycles.
AB  - PURPOSE: The present study investigated the effect of bladder distension on in
      vitro fertilization and embryo transfer (IVF-ET) results. METHODS: The study
      comprised 796 patients after successful transvaginal oocyte pickup and IVF, who,
      on the basis of bladder filling for ET, were divided into two groups. In group E,
      385 patients underwent ET with an empty bladder, and in group F, 411 patients
      underwent ET with a full bladder. RESULTS: Sixty-four pregnancies were achieved
      in group E (16.6%), compared to 110 pregnancies in group F (26.8%, P = 0.006). A
      similar pregnancy loss rate was observed in both groups, 13 in group E (20.3%)
      and 29 in group F (26.4%; P = NS). CONCLUSIONS: A significantly higher pregnancy
      rate was achieved with routine bladder distension before ET, probably
      attributable to the smooth and easy insertion of the ET catheter.

PMID- 9013309
TI  - Direct gamete uterine transfer in patients with tubal absence or occlusion.
AB  - PURPOSE: Our aim was to examine the potential of the uterine cavity to affect
      fertilization and early embryo development. DESIGN: A prospective IRB-approved
      protocol for patients fulfilling study eligibility criteria was used. METHODS:
      Patients studied included those with primary or secondary infertility, aged less
      than 38 years, with no history of severe male-factor infertility, and with
      hysterosalpingogram- and laparoscopic-confirmed bilateral proximal tubal
      occlusion. Superovulation induction was accomplished with a combination of GnRH
      agonist and menotropins, with serum hormonal and sonographic monitoring. Within
      24 hr prior to, and again at the time of, ovulatory hCG administration,
      progesterone (P4) was given. Sonographic-guided transvaginal retrieval was
      performed 35 hr after hCG. Between four and six oocytes were returned to the
      uterine cavity, admixed with sperm, immediately following retrieval. Luteal
      support consisted of daily P4 administration. RESULTS: Of the 20 patients
      recruited for the study, all completed the retrieval and transfer procedure. A
      total of four clinical pregnancies was achieved, with one early first-trimester
      loss, one late first-trimester loss (Trisomy 14), and two healthy term infants
      delivered. IVF of surplus oocytes demonstrated a 82.5% fertilization rate and
      66.7% cleavage following cryopreservation. CONCLUSIONS: Human fertilization can
      be achieved through direct uterine transfer of gametes. Furthermore,
      administration of P4 prior to the ovulatory dose of hCG is compatible with in
      vitro or in vivo fertilization and implantation.

PMID- 9013310
TI  - Synthesis of early pregnancy factor using red deer (Cervus elaphus) as a delayed
      implantation model.
AB  - PURPOSE: This study measured serum early pregnancy factor (EPF) in pregnant red
      deer (Cervus elaphus) and ascertained whether EPF synthesis is associated with
      implantation. METHODS: Serial serum samples were taken from mated hinds up to 42
      days postconception and analyzed for EPF activity using the rosette inhibition
      test. EPF activity was then correlated with calving records and stages of
      preimplantation development. RESULTS: EPF was detected in all pregnant animals,
      with a twin pregnancy giving increased EPF activity. Three animals gave an EPF
      response following fertilization but failed to continue beyond the
      preimplantation embryo stage. The increase in EPF synthesis previously associated
      with implantation in other mammals occurred at the blastocyst stage in red deer.
      CONCLUSIONS: EPF synthesis in red deer (Cervus elaphus) is consistent with the
      preimplantation period, as occurs in other mammals. However, the second phase of
      the biphasic increase in early pregnancy factor production is associated with
      blastocyst formation, not implantation.

PMID- 9013306
TI  - The role of a human chorionic gonadotropin burst in in vitro fertilization.
AB  - FINDINGS: No oocytes were found during four ovum pickups (OPU), despite a
      satisfactory ovarian response to controlled ovarian hyperstimulation. After the
      first attempt failed in the fourth case, five eggs were retrieved, fertilized,
      and cleaved after cycle rescue with hCG. CONCLUSIONS: Whenever oocytes are not
      aspirated during OPU due to a lack of hCG administration, the cycle may be
      rescued if 10,000 IU of hCG is injected immediately and OPU planned for 33-36 hr
      later.

PMID- 9013314
TI  - A case of primary ovarian pregnancy after in vitro fertilization and embryo
      transfer.

PMID- 9013312
TI  - Deleterious effect of equilibration temperature on the toxicity of propanediol
      during cryopreservation of mouse zygotes.
AB  - PURPOSE: Our aim was to determine the effect of temperature and incubation time
      on the toxicity of propanediol on mouse zygotes. METHOD: Zygotes were pooled and
      randomly allocated to one of the treatment groups. Zygotes were incubated in PBS
      or PBS containing 1.5M propanediol at 37 degrees C or room temperature (RT) for
      up to 30 min, washed, and cultured. Similarly, zygotes were incubated at 4
      degrees C or RT for 30 min and either washed and cultured or frozen-thawed,
      washed, and cultured. Zygotes were examined at 24, 48, and 96 hr of culture and
      embryo quality was determined. RESULTS: Exposure of zygotes to 1.5 M propanediol
      at 37 degrees C significantly impaired first cleavage and blastocyst formation
      compared to exposure at RT (P < 0.0007). Incubation of zygotes for more than 5
      min at 37 degrees C significantly reduced embryo development (P < 0.00001).
      Exposure to propanediol at 4 degrees C results in similar embryo development
      before and after freeze-thawing compared to exposure at RT. CONCLUSIONS:
      Propanediol is toxic to mouse zygotes in a temperature- and time-dependent
      fashion. Cryopreservation of zygotes after exposure at 4 degrees C appears to be
      no better than after exposure at RT.

PMID- 9013311
TI  - The change in tenascin expression in mouse uterus during early pregnancy.
AB  - PURPOSE: Our aim was to examine the changes in spatiotemporal tenascin (TN)
      expression in mouse uterus during early pregnancy, when the uterine tissue
      undergoes a tremendous restructuring. METHODS: Using immunohistochemistry and in
      situ hybridization, the changes in distribution of TN protein in mouse uterine
      tissues in pregnancy Day 0 through Day 5 were analyzed. RESULTS: Immunoreactive
      TN and TN mRNA were expressed in the basement membrane of the epithelium as well
      as in the smooth muscle layer, and their distribution shifted from the
      subbasement region on Day 0-3 to the smooth muscle layer on Days 4 and 5.
      CONCLUSIONS: These results indicate that TN expression in the uterus during early
      pregnancy is spatiotemporally different and may be regulated by a different
      mechanism.

PMID- 9013313
TI  - Ooplasmic round spermatid nuclear injection procedures as an experimental
      treatment for nonobstructive azoospermia.
AB  - PURPOSE: Our objective was to apply ooplasmic round spermatid nuclear injections
      for the treatment of nonobstructive azoospermia. MATERIALS: Participants were
      nine azoospermic men who had previously undergone diagnostic testicular biopsy.
      Spermatogenetic arrest was diagnosed at the round spermatid stage (n = 6) or
      primary spermatocyte stage (n = 3). A second (therapeutic) testicular biopsy was
      performed and round spermatid nuclei were recovered from all the participants.
      RESULTS: Forty-nine mature oocytes were successfully injected with nuclei and
      then cultured for 72 hr. Twenty-four embryos were transferred to nine women. No
      pregnancy was achieved. CONCLUSIONS: Round spermatids can be recovered from
      therapeutic testicular biopsy material of men negative for round spermatids in
      previous routine diagnostic testicular biopsy specimens. Round spermatid nuclear
      injections may play a role in the treatment of nonobstructive azoospermia.

PMID- 9013304
TI  - An open multicenter study to compare the efficacy of intraperitoneal insemination
      and intrauterine insemination following multiple follicular development as
      treatment for unexplained infertility.
AB  - PURPOSE: This multicenter study was carried out to compare the efficacy of
      intrauterine insemination (IUI) and intraperitoneal insemination (IPI) associated
      with multiple follicular development as treatment for unexplained infertility.
      METHOD: A total of 205 couples completed the trial. Sixty-seven couples underwent
      treatment with IPI (group A) and 138 couples underwent treatment with IUI (group
      B). RESULTS: Clinical pregnancy was obtained in 23 couples in group A (pregnancy
      rate: 34.3%) and in 36 couples in group B (pregnancy rate: 26.1%). No significant
      difference was observed between group A and group B. As for the evolution of
      pregnancies and the incidence of twin pregnancies, no significant difference was
      observed between the two groups. CONCLUSIONS: Because IUI and IPI allow us to
      obtain same results and IPI is more invasive than IUI, the latter technique can
      be considered the method of choice and IPI should be used when IUI is difficult
      to perform, as in the presence of a tight cervical canal.

PMID- 9013326
TI  - Assembly of ring canals in the male germ line from structural components of the
      contractile ring.
AB  - Stable intercellular bridges called ring canals form following incomplete
      cytokinesis, and interconnect mitotically or meiotically related germ cells. We
      show that ring canals in Drosophila melanogaster males are surprisingly different
      from those previously described in females. Mature ring canal walls in males lack
      actin and appear to derive directly from structural proteins associated with the
      contractile ring. Ring canal assembly in males, as in females, initiates during
      cytokinesis with the appearance of a ring of phosphotyrosine epitopes at the site
      of the contractile ring. Following constriction, actin and myosin II disappear.
      However, at least four proteins present at the contractile ring remain: the three
      septins (Pnut, Sep1 and Sep2) and anillin. In sharp contrast, in ovarian ring
      canals, septins have not been detected, anillin is lost from mature ring canals
      and filamentous actin is a major component. In both males and females, a highly
      branched vesicular structure, termed the fusome, interconnects developing germ
      cells via the ring canals and is thought to coordinate mitotic germ cell
      divisions. We show that, in males, unlike females, the fusome persists and
      enlarges following cessation of the mitotic divisions, developing additional
      branches during meiosis. During differentiation, the fusome and its associated
      ring canals localize to the distal tip of the elongating spermatids.

PMID- 9013328
TI  - Integrin alpha 6B beta 1 is involved in kidney tubulogenesis in vitro.
AB  - Laminin-1 has previously been shown to be of major importance for the development
      of kidney tubules. Antibodies against fragments E8 and E3 of laminin-1 perturb
      kidney development in vitro. We here studied expression of integrins alpha 6 beta
      1 and alpha 6 beta 4, two known laminin receptors, during kidney development.
      Integrin beta 1 subunit could be detected by immunofluorescence on all cell types
      of embryonic mouse kidney, but we could not detect integrin beta 4 subunit in
      embryonic kidney by immunofluorescence or by in situ hybridization. The presence
      of integrin alpha 6 subunit in all epithelia of embryonic kidney was demonstrated
      by immunofluorescence and by in situ hybridization. RT-PCR showed that alpha 6B
      is the major splice variant in embryonic kidney. During in vitro conversion of
      nephrogenic mesenchyme to epithelial tubules, a strong increase in the expression
      of the 6 kb mRNA for alpha 6 integrin subunit was seen by northern blotting at
      the onset of epithelial morphogenesis, on day two of culture. Immunoprecipitation
      of extracts from embryonic kidney with antibodies against alpha 6 subunit yielded
      bands corresponding to the expected size of beta 1 integrin subunit but not of
      beta 4 subunit. Monoclonal antibodies against either alpha 6 or beta 1 subunit
      but not against E-cadherin blocked kidney tubulogenesis in vitro. This suggests
      that integrin alpha 6B beta 1 is involved in kidney tubulogenesis in vitro.
      Another possibility is that the antibodies against integrin alpha 6 and beta 1
      subunit cause abnormal signalling by the integrin.

PMID- 9013329
TI  - p230 is associated with vesicles budding from the trans-Golgi network.
AB  - Transport vesicle formation requires the association of cytosolic proteins with
      the membrane. We have previously described a brefeldin-A sensitive, hydrophilic
      protein (p230), containing a very high frequency of heptad repeats, found in the
      cytosol and associated with Golgi membranes. We show here that p230 is localised
      on the trans-Golgi network, by immunogold labeling of HeLa cell cryosections
      using alpha 2,6 sialyltransferase as a compartment-specific marker. The role of G
      protein activators on the binding of p230 to Golgi membranes and in vesicle
      biogenesis has been investigated. Treatment of streptolysin-O permeabilised HeLa
      cells with either GTP gamma S or AlF4- resulted in accumulation of p230 on Golgi
      membranes. Furthermore, immunolabeling of isolated Golgi membranes treated with
      AlF4-, to induce the accumulation of vesicles, showed that p230 is predominantly
      localised to the cytoplasmic surface of trans-Golgi network-derived budding
      structures and small coated vesicles. p230-labeled vesicles have a thin
      (approximately 10 nm) electron dense cytoplasmic coat and could be readily
      distinguished from clathrin-coated vesicles. Dual immunogold labeling of
      perforated cells, or of cryosections of treated Golgi membranes, revealed that
      p230 and the trans-Golgi network-associated p200, which we show here to be
      distinct molecules, appear to be localised on separate populations of vesicles
      budding from the trans-Golgi network. These results strongly suggest the presence
      of distinct populations of non-clathrin coated vesicles derived from the trans
      Golgi network. As p230 recycles between the cytosol and buds/vesicles of TGN
      membranes, a process regulated by G proteins, we propose that p230 is involved in
      the biogenesis of a specific population of non-clathrin coated vesicles.

PMID- 9013327
TI  - Immortalised mouse submandibular epithelial cell lines retain polarised
      structural and functional properties.
AB  - The mouse submandibular gland (SMG) is an excellent model for the study of many
      important biological phenomena such as hormonal regulation of differentiation,
      neurotransmitter control of secretion, epithelial transport, exocytosis and
      endocytosis as well as the regulation of mouse SMG specific gene expression, in
      particular, NGF, EGF and renin. The postnatal development and sexual dimorphism
      of the mouse gland permits the isolation of male SMGs of different ages,
      corresponding to different stages of differentiation, particularly with respect
      to the cytodifferentiation of ductal cell types. We have immortalized SMG
      epithelial cell lines using mice transgenic for the large T antigen of SV40 or
      polyoma viruses. Epithelial clusters from the dissected glands were placed in
      culture and cell lines were established from the immortalized population. Two
      cell lines, SIMS and SIMP, which retain structural and functional
      characteristics, are described here. The cell lines are immortalised but not
      transformed, as judged by the absence of anchorage independent growth potential
      and the lack of tumour formation in athymic nude mice. Confocal and electron
      microscopy examination demonstrate that SIMP and SIMS cells express E-cadherin
      and ZO-1 and have features of polarised epithelial cells. In addition, they form
      spherical cysts with a wide lumen when grown in type I collagen gels. When grown
      on a filter support SIMS cells form a tight monolayer, exhibit vectorial
      transport function and show exclusive Na+, K(+)-ATPase localisation to the
      basolateral domain. We determined the cell type restricted expression of
      cytokeratin markers in the mouse SMG in vivo and we demonstrate that SIMS and
      SIMP cell lines express duct-specific cytokeratins. Finally, the expression of a
      set of differentiation markers, including EGF, NGF and renin, was detected by RT
      PCR and by indirect immunofluorescence staining in these lines. Thus, these
      polarised ductal cell lines, as well as having important intrinsic properties,
      represent well characterised mouse epithelial models which, until now, have not
      been readily available for cellular studies.

PMID- 9013330
TI  - Oscillating mitotic newt lung cell kinetochores are, on average, under tension
      and rarely push.
AB  - Experimentally introduced tension on kinetochores and their centromeres has been
      shown to stabilize kinetochore attachment to microtubules, modify kinetochore
      directional instability, and regulate cell-cycle progression into anaphase. In
      mitosis, kinetochore tension and the stretch of centromere chromatin are produced
      by the movement of sister kinetochores toward opposite poles and astral ejection
      forces on the chromosome arms. However, newt lung cell kinetochores oscillate
      between poleward and away from the pole motility states throughout mitosis,
      indicating kinetochores are not under constant tension. To test whether
      kinetochores are under net tension while they are oscillating, and how often they
      are under compression and pushing into the chromosome, we measured the distance
      between sister kinetochores in newt lung cells using both video-enhanced
      differential interference contrast microscopy (VE-DIC) and immunofluorescence
      microscopy. We found that for chromosomes in which sister kinetochores are
      attached to opposite spindle poles, centromeres are, on average, stretched (2.2
      microns in living cells and 1.8 microns in fixed cells) with respect to the inter
      kinetochore 'rest' length (1.1 microns in living and fixed cells). For
      chromosomes in which only one kinetochore is attached to the spindle, the
      centromere chromatin associated with the tethered kinetochore is, on average,
      stretched to approximately half of the average inter-kinetochore distance
      measured for chromosomes in which both kinetochores are attached. We conclude
      that while newt lung cell kinetochores oscillate between states of P and AP
      movement, they are under tension approximately 90% of the time and under
      compression less than 6% of the time.

PMID- 9013331
TI  - Calcium-dependent bidirectional power stroke of the dynein arms in sea urchin
      sperm axonemes.
AB  - Active sliding between doublet microtubules of sea urchin sperm axonemes that
      were demembranated with Triton X-100 in the presence or absence of calcium was
      induced with ATP and elastase at various concentrations of Ca2+ to examine the
      effects of Ca2+ on the direction of the power stroke of the dynein arms. Dark
      field light microscopy of microtubule sliding revealed that the sliding from the
      axonemes demembranated with Triton and millimolar calcium and disintegrated with
      ATP and elastase showed various patterns of sliding disintegration, including
      loops of doublet microtubules formed near the head or the basal body. These loops
      were often thicker than the remaining axonemal bundle. In contrast, only thinner
      loops were found from the axonemes demembranated with Triton in the absence of
      calcium and disintegrated with ATP and elastase at high Ca2+ concentrations.
      Electron microscopic examination of the direction of microtubule sliding showed
      that the doublet microtubules in the axonemes demembranated in the presence of
      millimolar calcium moved toward the base of the axonemes by the dynein arms on
      the adjacent doublet microtubule as well as by their own dynein arms. Doublet
      microtubules in the axonemes demembranated in the absence of calcium moved toward
      the base of the axonemes only by their own dynein arms. Similar observations have
      been obtained from the axonemes from which the outer dynein arms were selectively
      extracted. From these observations, we can conclude that the dynein arms generate
      force in both directions and this feature of the dynein arms arises from at least
      the inner dynein arms.

PMID- 9013332
TI  - An Aplysia cell adhesion molecule associated with site-directed actin filament
      assembly in neuronal growth cones.
AB  - During neuronal growth cone-target interactions, a programmed sequence of
      cytoskeletal remodeling has been described, involving increased actin assembly at
      the target site and directed microtubule extension into it. The cell adhesion
      protein apCAM rapidly accumulates at such interaction sites, suggesting a
      possible role in regulating cytoskeletal remodeling. To test this hypothesis we
      crosslinked apCAM to varying degrees with antibodies. Secondary immunocomplexes
      exhibited a classical patching and capping response; in contrast, high density
      crosslinking of apCAM by antibody coated beads triggered localized actin assembly
      accompanied by formation of tail-like actin structures referred to as
      inductopodia. When beads were derivatized with increasing amounts of anti-apCAM
      they displayed three sequential dose-dependent kinetic states after binding: (1)
      lateral diffusion in the plane of the membrane; (2) restricted diffusion due to
      coupling with underlying F-actin; and (3) translocation in the plane of the
      membrane driven by de novo actin filament assembly local to bead binding sites,
      i.e. inductopodia formation. In contrast, lectin coated beads were far less
      efficient in triggering inductopodia formation despite demonstrated membrane
      protein binding. This work provides evidence that crosslinking of a diffusable
      membrane protein, apCAM, to threshold levels, can trigger highly localized actin
      filament assembly and rapid remodeling of neuronal cytoarchitecture.

PMID- 9013333
TI  - Integrin-dependent induction of early growth response genes in capillary
      endothelial cells.
AB  - Studies were carried out to explore how extracellular matrix molecules, such as
      fibronectin (FN), promote capillary endothelial (CE) cell growth. When G0
      synchronized cells were plated on FN-coated dishes, expression of the immediate
      early mRNAs, c-fos, c-myc and c-jun, was rapidly induced, even in the absence of
      serum or soluble growth factors. Moreover, plating cells on different FN
      densities (5-200 micrograms/150 mm dish), resulted in a dose-dependent increase
      in the steady state levels of these mRNAs. Addition of FGF potentiated gene
      activation and was required for maximal DNA synthesis, however, the overall
      steady-state level of gene induction was dictated primarily by the density of
      immobilized FN. Expression of junB also was induced when suspended cells bound
      RGD-peptide coated microbeads that promote integrin clustering, but not when the
      suspended cells bound beads coated with other receptor ligands (e.g. acetylated
      low density protein) or when they were stimulated by soluble FN or FGF in the
      absence of substrate adhesion. c-Jun exhibited a similar requirement for gene
      induction except that it also was partially induced by binding to soluble FN
      alone. In contrast, c-fos expression was induced by all stimuli tested.
      Interestingly, inhibition of Na+/H+ exchange using hexamethylene-amiloride
      prevented most of the FN-induced increase in c-jun expression whereas it was
      relatively ineffective when cells were simultaneously stimulated by both FN and
      FGF. These data demonstrate that cell adhesion to extracellular matrix and
      associated integrin binding can directly activate signaling cascades in quiescent
      CE cells that lead to induction of immediate-early genes associated with the
      G0/G1 transition and thereby, stimulate these cells to reenter the growth cycle.

PMID- 9013334
TI  - The novel human protein serine/threonine phosphatase 6 is a functional homologue
      of budding yeast Sit4p and fission yeast ppe1, which are involved in cell cycle
      regulation.
AB  - We identified a novel human protein serine/threonine phosphatase cDNA, designated
      protein phosphatase 6 (PP6) by using a homology-based polymerase chain reaction.
      The predicted amino acid sequence indicates a 35 kDa protein showing high
      homology to other protein phosphatases including human PP2A (57%), human PP4
      (59%), rat PPV (98%), Drosophila PPV (74%), Schizosaccharomyces pombe ppe1 (68%)
      and Saccharomyces cerevisiae Sit4p (61%). In human cells, three forms of PP6 mRNA
      were found with highest levels of expression in testis, heart and skeletal
      muscle. The PP6 protein was detected in lysates of human heart muscle and in bull
      testis. Complementation studies using a temperature sensitive mutant strain of S.
      cerevisiae SIT4, which is required for the G1 to S transition of the cell cycle,
      showed that PP6 can rescue the mutant growth arrest. In addition, a loss of
      function mutant of S. pombe ppe1, described as a gene interacting with the
      pim1/spi1 mitotic checkpoint and involved in cell shape control, can be
      complemented by expression of human PP6. These data indicate that human PP6 is a
      functional homologue of budding yeast Sit4p and fission yeast ppe1, implying a
      function of PP6 in cell cycle regulation.

PMID- 9013335
TI  - Evidence for a functional link between Rab3 and the SNARE complex.
AB  - Rab3 is a monomeric GTP-binding protein associated with secretory vesicles which
      has been implicated in the control of regulated exocytosis. We have exploited
      Rab3 mutant proteins to investigate the function of Rab3 in the process of
      neurotransmitter release from Aplysia neurons. A GTPase-deficient Rab3 mutant
      protein was found to inhibit acetylcholine release suggesting that GTP hydrolysis
      by Rab3 is rate-limiting in the exocytosis process. This effect was abolished by
      a mutation in the effector domain, and required the association of Rab3 with
      membranes. In order to determine the step at which Rab3 interferes with the
      secretory process, tetanus and botulinum type A neurotoxins were applied to
      Aplysia neurons pre-injected with the GTPase-deficient Rab3 mutant protein. These
      neurotoxins are Zn(2+)-dependent proteases that cleave VAMP/synaptobrevin and
      SNAP-25, two proteins which can form a ternary complex (termed the SNARE complex)
      with syntaxin and have been implicated in the docking of synaptic vesicles at the
      plasma membrane. The onset of toxin-induced inhibition of neurotransmitter
      release was strongly delayed in these cells, indicating that the mutant Rab3
      protein led to the accumulation of a toxin-insensitive component of release.
      Since tetanus and botulinum type A neurotoxins cannot attack their targets,
      VAMP/synaptobrevin and SNAP-25, when the latter are engaged in the SNARE complex,
      we propose that Rab3 modulates the activity of the fusion machinery by
      controlling the formation or the stability of the SNARE complex.

PMID- 9013336
TI  - Cell cycle-dependent phosphorylation of the 77 kDa echinoderm microtubule
      associated protein (EMAP) in vivo and association with the p34cdc2 kinase.
AB  - The most abundant microtubule-associated protein in sea urchin eggs and embryos
      is the 77 kDa echinoderm microtubule-associated protein (EMAP). EMAP localizes to
      the mitotic spindle as well as the interphase microtubule array and is a likely
      target for a cell cycle-activated kinase. To determine if EMAP is phosphorylated
      in vivo, sea urchin eggs and embryos were metabolically labeled with 32PO4 and a
      monospecific antiserum was used to immunoprecipitate EMAP from 32P-labeled eggs
      and embryos. In this study, we demonstrate that the 77 kDa EMAP is phosphorylated
      in vivo by two distinct mechanisms. In the unfertilized egg, EMAP is
      constitutively phosphorylated on at least five serine residues. During the first
      cleavage division following fertilization, EMAP is phosphorylated with a cell
      cycle-dependent time course. As the embryo enters mitosis, EMAP phosphorylation
      increases, and as the embryo exits mitosis, phosphorylation decreases. During
      mitosis, EMAP is phosphorylated on 10 serine residues and two-dimensional
      phosphopeptide mapping reveals a mitosis-specific site of phosphorylation. At all
      stages of the cell cycle, a 33 kDa polypeptide copurifies with the 77 kDa EMAP,
      regardless of phosphorylation state. Antibodies against the cdc2 kinase were used
      to demonstrate that the 33 kDa polypeptide is the p34cdc2 kinase. The p34cdc2
      kinase copurifies with the mitotic apparatus and immunostaining indicates that
      the p34cdc2 kinase is concentrated at the spindle poles. Models for the
      interaction of the p34cdc2 kinase and the 77 kDa EMAP are presented.

PMID- 9013337
TI  - Expression of fibulin-2 by fibroblasts and deposition with fibronectin into a
      fibrillar matrix.
AB  - The extracellular matrix protein fibulin-2 was shown to be a typical product of
      cultured human and mouse fibroblasts by several immunological assays. It is
      secreted and deposited in cells and tissues as a disulfide-bonded oligomer
      identical in size to the previously described recombinant fibulin-2. Most of the
      fibroblast fibulin-2 is deposited into a dense fibrillar meshwork which requires
      treatment with EDTA and/or 6 M urea for solubilization. Fibulin-2 and fibronectin
      are synthesized at equivalent levels and both colocalize in the fibrils as shown
      by immunofluorescence. Metabolic labelling and pulse-chase studies demonstrated
      fibulin-2 oligomers in detergent extracts of cells and their rapid translocation
      to extracellular EDTA-sensitive assembly forms. Unlike for fibronectin and
      fibulin-1 only a little fibulin-2 was found in the cell culture medium.
      Immunogold staining of confluent human fibroblasts showed localization of fibulin
      2 to a fine meshwork or bundles of amorphous microfibrils in the matrix. This
      also demonstrated a distinct colocalization of fibulin-2 and fibronectin at the
      electron microscope level, indicating that the interaction between these two
      protein shown in in vitro assays may also exist in situ. No distinct
      colocalization of both proteins could, however, be observed with cross-striated
      fibrils of collagen I and collagen VI microfibrils.

PMID- 9013340
TI  - The effects of cytochalasin D and phorbol myristate acetate on the apical
      endocytosis of ricin in polarised Caco-2 cells.
AB  - Apical endocytosis of 125I-ricin in Caco-2 cells was inhibited > 95% by
      hypertonic and/or acid media, consistent with the major uptake route being
      clathrin-mediated. The presence of apical cell surface bound ricin-gold in
      clathrin coated pits and vesicles was observed by electron microscopy. An
      electron microscopic investigation in which ricin-gold bound to the apical
      surface was quantitated, showed that cytochalasin D, which inhibits apical but
      not basolateral endocytosis, prevented movement of ricin-gold along the
      microvillar surface. This was consistent with an actin bound mechanochemical
      motor within microvilli driving the movement of membranous components towards the
      cell body. Cytochalasin D also caused an increase in the number of coated pits
      observed at the apical cell surface relative to the number observed in untreated
      cells. Stimulation of apical endocytosis of ricin by phorbol 12-myristate 13
      acetate showed the characteristics of being mediated by protein kinase C, was not
      due to an effect on ricin movement along the microvillar surface, and may be
      explained by increases in formation and pinching off of clathrin coated pits at
      the apical cell surface.

PMID- 9013341
TI  - A novel bone marrow frozen section assay for studying hematopoietic interactions
      in situ: the role of stromal bone marrow macrophages in erythroblast binding.
AB  - Bone marrow macrophages are found in intimate contact with erythroblasts. Exact
      mechanisms and functions of this interaction are unclear. New insights into
      erythroblast binding were obtained using a newly developed bone marrow frozen
      section assay. This modified Woodruff and Stamper assay has some important
      advantages compared to other adhesion assays. Erythroblasts specifically adhered
      to bone marrow macrophages forming clusters, as appear in vivo. Selective
      depletion of bone marrow macrophages by intravenous injection of dichloromethyl
      enediphosphonate resulted in a release of immature erythroid cells to the
      peripheral blood. Furthermore no erythroblasts adhered to bone marrow sections
      without macrophages. Evaluating the binding of erythroblasts to bone marrow
      macrophages we found that this binding is temperature and cation dependent. The
      receptor for erythroblasts present on macrophages recognizes a sialyated protein
      as ligand on erythroblasts, since neuraminidase treatment of erythroblasts
      resulted in a decrease in binding. A possible candidate for the erythroblast
      receptor on macrophages is the ED2 antigen. ED2 is a differentiation antigen
      present on resident macrophages that has some biochemical features characteristic
      of an adhesion molecule. Erythroblast binding to bone marrow was inhibited using
      a monoclonal antibody directed against ED2.

PMID- 9013338
TI  - Isolation and characterization of early endosomes, late endosomes and terminal
      lysosomes: their role in protein degradation.
AB  - Although endosomal proteolysis has been reported (e.g. for peptide hormones and
      lysosomal enzymes), lysosomes are believed to be the main site of degradation in
      the endocytic pathway. We have studied the separate roles of lysosomes and
      prelysosomal endocytic organelles in the degradation of ovalbumin in J774 cells.
      The ovalbumin was labelled with 125I-tyramine cellobiose (125I-TC-ova). The
      labelled degradation products formed from this probe are trapped at the site of
      formation. To separate lysosomes efficiently from prelysosomal endocytic
      organelles we allowed the cells to endocytose a pulse of colloidal gold particles
      complexed with ovalbumin. By combining this density shift technique with
      subcellular fractionation of a postnuclear supernatant in Percoll gradients we
      could isolate three fractions that were sequentially involved in the endocytic
      pathway: a light Percoll fraction, a dense Percoll fraction and a gold fraction.
      The light Percoll fraction contained early endosomes since it was transferrin
      positive and received endocytic markers such as ovalbumin and horseradish
      peroxidase (HRP) early (< 5 minutes) after internalization. The dense Percoll
      fraction was transferrin negative, rab7 positive and received endocytic markers
      after 10-15 minutes of internalization. The gold-filled fraction was negative for
      both transferrin and rab7 but highly enriched in the lysosomal enzyme beta
      hexosaminidase and was therefore defined as a lysosome. To study the role of
      endosomes and lysosomes in the degradation of endocytosed material we allowed the
      cells to take up (via the mannose receptor) 125I-TC-ova. It was found that the
      main degradation of 125I-TC-ova (measured as acid soluble radioactivity trapped
      in the organelle) took place in the late endosomes (and not in the lysosomes
      containing the bulk of the lysosomal enzymes). Our data therefore suggest that
      the late endosomes operate as an early lysosomal compartment. The terminal
      lysosomes may serve as storage bodies for acid hydrolases that may be called upon
      when needed (for instance during phagocytosis).

PMID- 9013342
TI  - The size control of fission yeast revisited.
AB  - An analysis was made of cell length and cycle time in time-lapse films of the
      fission yeast Schizosaccharomyces pombe using wild-type (WT) cells and those of
      various mutants. The more important conclusions about 'size controls' are: (1)
      there is a marker in G2 in WT cells provided by a rate change point (RCP) where
      the linear rate of length growth increases by approximately 30%. The period
      before this RCP is dependent on size and can be called a 'sizer'. The period
      after the RCP is nearly independent of size and can be called a 'timer'. The
      achievement of a critical threshold size is at or near the RCP which is on
      average at about 0.3 of the cycle (halfway through G2). This is much earlier than
      was previously believed. (2) The RCP is at about the time when H1 histone kinase
      activity and the B type cyclin cdc13 start to rise in preparation for mitosis.
      The RCP is also associated with other metabolic changes. (3) In wee1 mutants, the
      mitotic size control is replaced by a G1/S size control which is as strong as the
      mitotic control. As in WT cells, there is a sizer which precedes the RCP followed
      by a timer but the RCP is at about the G1/S boundary and has a larger increase
      (approximately 100%) in rate. (4) cdc25 is not an essential part of the size
      control at mitosis or at the G1/S boundary. (5) Three further situations have
      been examined in which the mitotic size control has been abolished. First,
      induction synchronisation by block and release of cdc2 and cdc10. In the largest
      oversize-cells which are produced, the RCP is pushed back to the beginning of the
      cycle. There is no sizer period but only a timer. Second, when both the
      antagonists wee1 and cdc25 are absent in the double mutant wee1-50 cdc25 delta.
      In this interesting situation there is apparently no mitotic size control and the
      cycle times are quantised. Third, in rum1 delta wee1-50 where the normal long G1
      in wee1 is much reduced, there is probably no size control either in G1 or in G2
      causing a continuous shortening of division length from cycle to cycle.

PMID- 9013339
TI  - TGN38-green fluorescent protein hybrid proteins expressed in stably transfected
      eukaryotic cells provide a tool for the real-time, in vivo study of membrane
      traffic pathways and suggest a possible role for ratTGN38.
AB  - The green fluorescent protein (GFP) of Aquorea victoria is fluorescent when
      expressed as a recombinant protein in eukaryotic cells and has been used as a
      convenient marker of gene expression in vivo. It has also been used as a marker
      of the intracellular targeting of recombinant fusion proteins (part GFP, part
      protein of interest) which have been transiently expressed in eukaryotic cells
      grown in tissue culture. Thus, the use of GFP has proved a useful tool to study
      intracellular events in real-time. However, some transiently transfected cells
      fail to express, or localise correctly, the GFP-tagged protein. Therefore the
      production of stable cell lines expressing GFP-tagged integral membrane proteins
      may be essential for long-term studies. The generation of stably transfected
      eukaryotic cells expressing an integral membrane protein with a known, but poorly
      characterised intracellular trafficking pathway, would provide useful reagents
      for future, more precise, analysis of that pathway. TGN38 is a type I integral
      membrane protein which cycles between the trans-Golgi network (TGN) and cell
      surface; at steady state it is localised to the TGN. As such, TGN38 is an ideal
      candidate for tagging with GFP. We have generated cDNA constructs encoding
      ratTGN38 tagged at either the N- or C terminus with GFP. Transiently transfected
      rat (NRK) cells expressed active fluorophore, but failed to show correct
      localisation of the fusion protein. In contrast, both constructs are
      appropriately localised in stably transfected NRK cells and both are fluorescent.
      Furthermore, the recombinant GFP-tagged proteins and the endogenous TGN38
      molecules show identical responses to drugs and temperature blocks known to
      perturb intracellular morphology and membrane traffic pathways. In fact
      morphological changes to the TGN induced by brefeldin A were observed at earlier
      time points than had been described previously using immunofluorescence analysis
      of fixed cells, thus validating the use of in vivo, real-time analysis of GFP
      tagged proteins. In addition, we show that (in contrast to the situation in COS
      cells) elevated expression of ratTGN38 in NRK cells does not lead to a
      fragmentation of the TGN; this has implications for the role which TGN38 is
      playing in the maintenance of the morphology of the TGN. The data we present
      demonstrate that: (i) it is possible to generate stable cell lines expressing
      integral membrane proteins tagged with GFP; (ii) the GFP tag remains fluorescent
      when expressed on either the cytosolic or the lumenal side of all membranes of
      the secretory pathway up to and including that of the TGN; (iii) the GFP tag does
      not interfere with the transport of TGN38 along the secretory pathway or its
      retention in the TGN; (iv) GFP remains fluorescent in cells which have been
      processed for immunofluorescence analysis (using either paraformaldehyde or
      methanol fixation); and (v) TGN38 plays a role in maintaining the morphology of
      the TGN. Thus, stably transfected cells expressing GFP-tagged integral membrane
      proteins can be used as effective tools for the real-time study of intracellular
      morphology and membrane traffic pathways in eukaryotic cells.

PMID- 9013347
TI  - Very high prevalence of hepatitis B and C in Bukharian Jewish immigrants to
      Israel.
AB  - In Israel, the reported prevalence of hepatitis-C virus (HCV) infection among
      blood donors is 0.44%. As we found a high prevalence of chronic hepatitis-B virus
      (HBV) and HCV infection in Jewish immigrants from Uzbekistan and Tajikistan
      (Bukharian Jews) among our general patient population, we determined the
      prevalence of HBV and HCV infection among "healthy" Bukharian Jewish immigrants
      by screening for HBV and HCV markers and risk factors in a population of
      Bukharian Jews in north Jerusalem. A total of 27 (26.5%) of 102 patients were
      anti-HCV positive (by ELISA and confirmation tests). The HCV positive patients
      were older and had a higher rate of liver enzyme abnormalities than were the HCV
      negative patients (56.5 +/- 2.3 versus 47.6 +/- 1.8, p = 0.003; and 14 of 27
      versus 7 of 75, p < 0.01, respectively). HCV-positive patients with liver enzyme
      abnormalities were younger than HCV-positive patients without liver enzyme
      abnormalities (52.5 +/- 3.0 versus 62.8 +/- 2.8, p = 0.02). Sixteen patients
      (15.7%) were hepatitis-B surface antigen (HBsAg) carriers, and only two of these
      HBsAg carriers had liver enzyme abnormalities. None of the HCV-positive patients
      were HBsAg carriers (0 of 27 among HCV-positive patients versus 16 of 75 among
      HCV-negative patients, p = 0.0055). Past infection with HBV was found in 67
      examinees (66%) (45 of 75 HCV-negative patients and 22 of 27 HCV-positive
      patients, p = 0.058). However, similar proportions of patients from both groups
      had past and present exposure to HBV [61 (81.3%) of 75 among HCV-negative
      patients versus 22 (81.5%) of 27 among HCV-positive patients]. Only 14 patients
      (13.7%) had no exposure to either HCV or HBV. Possible risk factors were use of
      nondisposable needles during mass vaccination in the U.S.S.R. or possible
      intrafamilial spread. The study concluded that immigrant Jews from former Asiatic
      U.S.S.R. republics have the highest rate of HCV positivity ever reported, and
      many of them have past and present HBV infection. Measures to prevent
      intrafamilial transmission of both viruses should be instituted.

PMID- 9013343
TI  - Meta-analysis of risk factors for peptic ulcer. Nonsteroidal antiinflammatory
      drugs, Helicobacter pylori, and smoking.
AB  - Attributable risk models describe the role of three risk factors for peptic ulcer
      and related serious upper gastrointestinal (GI) events. The factors-nonsteroidal
      antiinflammatory drugs (NSAIDs), Helicobacter pylori, and cigarette smoking-have
      been identified as major risk factors for peptic ulcer in numerous clinical and
      epidemiologic studies. Overall risk ratios for each risk factor were based on
      meta-analyses of English-language studies of risk for peptic ulcer-related GI
      events. Exposure estimates for factors used data from North American populations.
      Summary risk and exposure values were computed for the general population, males
      and females separately, and the elderly. Hypothetical models of multiple factor
      attributable risks were developed using population attributable risk percent
      calculated from these summary values. General population attributable risk
      percent were as follows: 24%, NSAIDs; 48%, H. pylori; and 23%, cigarette smoking.
      Based on these numbers, the "no interaction" attributable risk model estimates
      that 95% of total peptic ulcer related risk is attributable to these factors in
      the general population. The "interaction" model attributes 89% of cases to these
      risk factors: 24%, NSAIDs alone; 31%, H. pylori alone; 34%, H. pylori/smoking
      combined. Between 89% and 95% of peptic ulcer-related serious upper GI events may
      be attributed to NSAID use, H. pylori infection, and cigarette smoking.

PMID- 9013346
TI  - Brucellosis and the gastrointestinal tract. The odd couple.
AB  - Though pathogenetically qualifying as an enteric fever, the gastroenterological
      manifestations of Brucella in humans are relatively uncommon. We present a
      typical case of Brucellosis with gastrointestinal symptoms and review these by
      organ involvement, ranging from the mild nonspecific, such as diarrhea and
      abdominal pain, to the pathologically distinct hepatic lesions, and to the rare
      colonic, pancreatic, and peritoneal involvement. The limited indications for
      diagnostic procedures, such as endoscopy and liver biopsy are discussed.

PMID- 9013345
TI  - Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia.
AB  - Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in
      which colorectal neoplasia has been described, but the incidence in the former
      condition may not be increased. We describe four patients with colorectal
      neoplasia associated with the ZES and review other published cases. Tissue ELISA
      with Adnab-9 antibody, a putative colorectal cancer risk marker, from a patient
      with ZES and from seven patients with acromegaly was compared to 13 controls at
      average risk for colorectal neoplasia. The patient with ZES without detectable
      colonic neoplasia and seven patients with acromegaly had increased binding of
      Adnab-9 in the colonic mucosa by ELISA. The difference was significant for the
      acromegaly patients compared to the controls (p < 0.05). The accumulated 34
      instances of colorectal neoplasia in ZES patients suggests that this association
      may not be rare. Adnab-9 expression, detectable in both ZES and acromegaly, may
      reflect predisposition to colorectal neoplasia in both hyper-secretory states.
      Therefore, while a basis for association of colorectal neoplasia and
      hypergastrinemia exists, the clinical data are not compelling enough to warrant
      surveillance of patients with ZES. To resolve this problem, more definitive case
      control studies should be conducted.

PMID- 9013344
TI  - Arthralgia as an early extraintestinal symptom of Whipple's disease. Report of
      five cases.
AB  - Five patients with Whipple's disease all suffered from arthralgia for a long time
      (15 years in one case) before developing gastrointestinal or other symptoms. In
      all patients, arthralgia was seronegative, and there was no evidence of joint
      destruction. Arthralgias were symmetric and migrating. Whipple's disease is part
      of the differential diagnosis of enteropathic arthralgia. Thereby, the polymerase
      chain reaction can be a helpful tool to prove Whipple's disease in difficult
      differential diagnosis.

PMID- 9013348
TI  - Mesalamine-induced hypersensitivity pneumonitis. A case report and review of the
      literature.
AB  - A 49-year-old man with Crohn's disease treated with prednisone and mesalamine (5
      ASA) developed worsening respiratory distress and fever. Symptoms improved after
      discontinuation of mesalamine. A rechallenge 3 months later caused similar
      pulmonary symptoms, confirming the association between the drug and the
      respiratory system. Mesalamine may cause hypersensitivity pneumonitis in patients
      with Crohn's disease.

PMID- 9013349
TI  - Nephrotic syndrome from 5-ASA for ulcerative colitis? Complicated by carcinoma of
      the colon and sclerosing cholangitis.
AB  - A patient with nephrotic syndrome had been treated with mesalazine for ulcerative
      colitis, and also had a carcinoma of the colon and sclerosing cholangitis. This
      seemingly unrelated series of complications gives us the opportunity to review
      the problem of nephropathy in ulcerative colitis.

PMID- 9013350
TI  - HCV hepatitis associated with anticardiolipin antibody and a cerebrovascular
      accident. Response to interferon therapy.
AB  - A 54-year-old man with chronic hepatitis C virus (HCV) developed
      quadrihemianopsia caused by lacunar brain infarction. Extensive evaluation
      revealed high titers of anticardiolipin antibodies (ACA). Following interferon
      treatment (6 x 10(6), three times a week for 2 months and 3 x 10(6) for another 7
      months), liver transaminase levels decreased to normal, HCV RNA in blood was no
      longer detectable, concomitantly with the disappearance of the ACA. The patient
      remained clinically stable without evidence for either HCV activity (RNA) or ACA
      or further thromboembolic events.

PMID- 9013351
TI  - Impact of human immunodeficiency virus infection on abdominal tuberculosis in
      western India.
AB  - We studied the seroprevalence of human immunodeficiency virus infection in
      patients with pulmonary tuberculosis and abdominal tuberculosis. We also assessed
      the clinical characteristics, risk factors, tuberculin status, site, and response
      to therapy of abdominal tuberculosis in human immunodeficiency virus (HIV)
      seropositive and HIV-seronegative patients. Volunteer blood donors (n = 8,395),
      patients with pulmonary tuberculosis (n = 387), and patients with abdominal
      tuberculosis (n = 108) were screened for HIV 1 and/or HIV 2 by enzyme-linked
      immunosorbent assay (ELISA; Torrent, India) and positivity reconfirmed by a
      repeat ELISA and Western blot test. The HIV seroprevalence in the abdominal
      tuberculosis patients (16.6%) was significantly higher compared with those with
      pulmonary tuberculosis (6.9%, p < 0.05) and volunteer blood donors (1.4%, p <
      0.01). Absolute lymphocyte counts did not differ between the HIV-seropositive and
      HIV-seronegative patients (2,044.94 +/- 830 vs 2,261.34 +/- 805/mm3, p = NS). The
      Mantoux reaction was larger in the HIV-seronegative group as compared with the
      HIV-seropositive group (14.8 mm vs. 9.5 mm, p < 0.05). Tuberculosis patients
      responded well to conventional antituberculosis drugs in standard doses
      regardless of their HIV status.

PMID- 9013353
TI  - Rapid progression of gastroesophageal junction adenocarcinoma after liver
      transplantation.

PMID- 9013354
TI  - Transgastric migration of a surgical sponge.

PMID- 9013352
TI  - Cocaine-induced ischemic colitis with small-vessel thrombosis of colon and
      gallbladder.
AB  - Ischemic colitis is a rare complication of cocaine abuse. To date, only 15
      reports have linked the use of cocaine to ischemic events of the small bowel and
      colon. We report ischemic colitis in a 36-year-old woman who admitted using crack
      cocaine twice, 1 and 2 days before onset of symptoms. Patchy areas of necrosis
      were grossly present in the resected transverse colon. In addition, the
      gallbladder showed edema and congestion of the wall on gross examination. On
      microscopy, the gallbladder as well as the colon were noted to have multiple
      small-vessel thrombi. Colonic mucosa showed ischemic necrosis. Cocaine abuse
      should be considered in the differential diagnosis of ischemic colitis,
      especially in a young adult.

PMID- 9013355
TI  - Retained surgical sponge: an unusual cause of intestinal obstruction.

PMID- 9013356
TI  - A good computed tomography in gallstone ileus.

PMID- 9013357
TI  - Neuroanatomy of the pain system and of the pathways that modulate pain.
AB  - We review many of the recent findings concerning mechanisms and pathways for pain
      and its modulation, emphasizing sensitization and the modulation of nociceptors
      and of dorsal horn nociceptive neurons. We describe the organization of several
      ascending nociceptive pathways, including the spinothalamic, spinomesencephalic,
      spinoreticular, spinolimbic, spinocervical, and postsynaptic dorsal column
      pathways in some detail and discuss nociceptive processing in the thalamus and
      cerebral cortex. Structures involved in the descending analgesia systems,
      including the periaqueductal gray, locus ceruleus, and parabrachial area, nucleus
      raphe magnus, reticular formation, anterior pretectal nucleus, thalamus and
      cerebral cortex, and several components of the limbic system are described and
      the pathways and neurotransmitters utilized are mentioned. Finally, we speculate
      on possible fruitful lines of research that might lead to improvements in therapy
      for pain.

PMID- 9013360
TI  - Effect of carpal tunnel syndrome on median nerve proximal conduction estimated by
      F-waves.
AB  - Slowing of median nerve proximal motor conduction in patients with carpal tunnel
      syndrome (CTS) could be considered as an indicator of an additional proximal
      lesion (double crush syndrome). The effect of CTS on proximal conduction was
      assessed by comparing motor velocities calculated by F-waves obtained from
      muscles with the same root and nerve supply but different median branches, one
      emerging before the carpal tunnel (pronator quadratus muscle) and one passing
      through the tunnel (abductor pollicis brevis). Data were obtained from 26
      patients with CTS and 21 age-matched healthy subjects. In the control group, the
      proximal (spinal cord and elbow) F-wave maximal velocity calculated when
      recording from abductor pollicis brevis (FCVmax-APB) was not different from the F
      wave maximal velocity calculated when recording from pronator quadratus (FCVmax
      PQ), while it was significantly different in the group of CTS patients,
      especially in patients with terminal motor latency greater than 4.5 ms
      (approximately 9% less, p = 0.001, Wilcoxon signed rank test). The study showed
      that median nerve proximal conduction velocity slowing in patients with CTS is
      restricted to the fibers that distally pass through the carpal tunnel and does
      not necessarily imply an additional proximal lesion. We suggest that comparison
      of FCVmax-APB and FCVmax-PQ could be useful when the question arises if a single
      (distal) or two (one distal, one proximal) lesions are responsible for a
      patient's symptoms.

PMID- 9013361
TI  - Suppressed cardiac and electroencephalographic arousal on apnea/hypopnea
      termination in elderly patients with cerebral infarction.
AB  - The goal of the present investigation is to show the clinical significance of
      arousal response at termination of apnea/hypopnea in patients with sleep apnea
      syndrome (SAS) after cerebral infarction. We polygraphically assessed "cardiac
      arousal," which is defined as an abrupt increase in heart rate at a termination
      of sleep apnea/hypopnea, and electroencephalographic (EEG) arousal. There were
      six elderly subjects, bedridden after cerebral infarction, with SAS aged 71-87
      years (mean 72.3 years) and 11 age-matched patients with SAS aged 61-78 years
      (mean 62.3 years) as controls. The following sleep parameters were measured:
      number of apneas per hour (apnea index [AI]), number of hypopneas per hour
      (hypopnea index [HI]), summation of the two (apnea/hypopnea index [AHI]), and
      duration in which nocturnal oxygen saturation was decreased below 90% (duration
      of SaO2 < 90%). We calculated the ratio of apnea/hypopnea per hour with cardiac
      arousal to total apnea/hypopneas (XI) (% cardiac arousal [XI/AHI x 100]) and the
      ratio of that with EEG arousal (YI) (% EEG arousal [YI/AHI x 100]). Between the
      two groups, we found no significant difference in body mass index, the ratio of
      central apnea to total apnea/hypopnea, AHI, duration of apnea/hypopnea, lowest
      SaO2, and duration of SaO2 < 90%. Compared with controls, % cardiac and % EEG
      arousals were significantly lower in patients with cerebral infarction. In
      contrast, the ratio of HI to AHI was significantly higher in patients with
      cerebral infarction than in control subjects. Our findings indicate that cardiac
      and EEG arousals at termination of apnea/hypopnea are significantly suppressed in
      elderly patients with SAS after cerebral infarction, which may provide useful
      information on the pathophysiology of SAS in patients with cerebrovascular
      disease.

PMID- 9013363
TI  - New immunosuppressive drugs in organ transplantation.
AB  - An examination of the mechanisms by which four new immunosuppressive drugs-
      rapamycin, mizoribine, mycophenolate mofetil, and 15-deoxyspergualin--exert their
      effects reveals three major categories. Rapamycin binds to an intracellular
      immunophilin. The resulting drug-immunophilin complex inhibits the action of
      cytokines, thus blocking the activation and proliferation of T cells. Mizoribine
      and mycophenolate mofetil are antimetabolites that inhibit a key enzyme in the de
      novo purine biosynthetic pathway. As a result, the proliferation of T cells and B
      cells is inhibited selectively compared with that of nonlymphoid cells because
      the salvage pathway is unavailable to lymphocytes. Finally, 15-deoxyspergualin
      has a unique mechanism of action, which includes suppressive effects on
      macrophage function, the induction of cytolytic T cells, B-cell reactivity, and
      antibody responses. The demonstrated synergism among certain immunosuppressants
      allows reduction in the dose of each agent to minimize the individual toxicities.
      As more of these new agents become available, it is likely that azathioprine will
      be replaced, and it may be possible to eliminate the need for long-term
      maintenance steroid therapy.

PMID- 9013362
TI  - Spatial filtering of multichannel electroencephalographic recordings through
      principal component analysis by singular value decomposition.
AB  - Principal component analysis (PCA) by singular value decomposition (SVD) may be
      used to analyze an epoch of a multichannel electroencephalogram (EEG) into
      multiple linearly independent (temporally and spatially noncorrelated)
      components, or features; the original epoch of the EEG may be reconstructed as a
      linear combination of the components. The result of SVD includes the components,
      expressible as time series waveforms, and the factors that determine how much
      each component waveform contributes to each EEG channel. By omission of some
      component waveforms from the linear combination, a new EEG can be reconstructed,
      differing from the original in useful ways. For example, artifacts can be removed
      and features such as ictal or interictal discharges can be enhanced by
      suppressing the remainder of the EEG. We developed a variation of this technique
      in which the factors that reconstruct the modified EEG from the original are
      stored as a matrix. This matrix is applied to multichannel EEG at successive
      times to create a new EEG continuously in real time, without redoing the time
      consuming SVD. This matrix acts as a spatial filter with useful properties. We
      successfully applied this method to remove artifacts, including ocular movement
      and electrocardiographic artifacts. Removal of myogenic artifacts was much less
      complete, but there was significant improvement in the ability to visualize
      underlying activity in the presence of myogenic artifacts. The major limitations
      of the method are its inability to completely separate some artifacts from
      cerebral activity, especially when both have similar amplitudes, and the
      possibility that a spatial filter may distort the distribution of activities that
      overlap with the artifacts being removed.

PMID- 9013364
TI  - Antioxidant vitamins and health.

PMID- 9013358
TI  - Clinical neurophysiology laboratory tests to assess the nociceptive system in
      humans.
AB  - This paper presents some currently available neurophysiological tools that are
      helpful in the clinical setting to evaluate and document neuropathic disturbances
      that may be associated with pain. The specific tests described in this discussion
      are quantitative sensory tests (QSTs), autonomic tests (ATs), microneurography
      (MCNG), and laser evoked potentials (LEPs). Quantitative sensory testing of the
      nociceptive system includes the thermal stimulation (TST) and current perception
      threshold (CPT) tests. The ATs applicable to some patients with pain are
      sudomotor and vasomotor tests. The quantitative sudomotor axon reflex test
      (QSART), resting sweat output (RSO), and sympathetic skin response (SSR) are the
      tests for sudomotor involvement. The vasomotor system is tested by measuring skin
      temperature (surface thermistor or thermography) at rest and, in some cases,
      after provocative maneuvers. In addition, MCNG (intraneural recording of single
      nerve fibers or fascicles of nerves) allows examiners to look directly at muscle
      and skin sympathetic efferent output in normal subjects without pain or with
      experimental pain and in patients with neuropathic pain. This technique also
      provides a means of studying the physiology of primary afferent fibers in persons
      with neurogenic pain. Recent development of LEPs that incorporate the use of
      painful infrared laser-induced stimuli allow selective study of the nociceptive
      system, both the central and peripheral portions.

PMID- 9013359
TI  - Stimulation of the central and peripheral nervous system for the control of pain.
AB  - After suffering some setbacks since its introduction in 1967, stimulation of the
      spinal and peripheral nervous systems has undergone rapid development in the last
      ten years. Based on principles enunciated in the Gate Control Hypothesis that was
      published in 1968, stimulation-produced analgesia [SPA] has been subjected to
      intensive laboratory and clinical investigation. Historically, most new clinical
      ideas in medicine have tended to follow a three-tiered course. Initial enthusiasm
      gives way to a reappraisal of the treatment or modality as side-effects or
      unanticipated problems arise. The last and third phase proceeds at a more
      measured pace as the treatment is refined by experience. This review is divided
      into three parts as it traces the progress of spinal cord stimulation [SCS] and
      peripheral nerve stimulation [PNS]. The review commences with a discussion of the
      theory of SCS and PNS, and is followed by early reports during which it became
      apparent that the modality is essentially only effective in the treatment of
      neuropathic pain. The last section describes the modern experience including
      efficacy in specific types of pain and concludes with recent accomplishments that
      dramatize the relief of pain which can be achieved in nonoperable peripheral
      vascular disease or myocardial ischemia. Over the years, a search for those
      transmitters that might be influenced by spinal cord stimulation focused on
      somatostatin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP),
      neurotensin and other amines, although only substance "P" was implicated. More
      recently, in animal studies, evidence that GABA-ergic systems are affected may
      explain the frequent successful suppression of allodynia that follows spinal cord
      stimulation. During the past eight years, much attention has been directed to
      studies that use a chronic neuropathic pain model. While PNS held significant
      promise as a pain relieving modality, early electrode systems and their surgical
      implantation yielded variable results due to evolving technical and surgical
      skills. These results dramatically reduced the continued development of PNS,
      which then gave way to a preoccupation with SCS. Modern development of SCS with
      outcome studies, particularly in relation to failed back surgery syndrome [FBSS]
      and the outcome of peripheral nerve surgery for chronic regional pain syndromes,
      has earned both modalities a place in the ongoing management of patients with
      intractable neuropathic pain. The last section, dealing with pain of peripheral
      vascular and myocardial ischemia, is perhaps one of the more exciting
      developments in stimulation produced analgesia and as the papers discussed
      demonstrate, can provide a level of analgesia and efficacy that is unattainable
      by other treatment modalities. SCS and PNS has an important role to play in the
      management of conditions that are otherwise refractory to conservative or other
      conventional management.

PMID- 9013367
TI  - Pharmacokinetics of ceftriaxone in patients undergoing continuous veno-venous
      hemofiltration.
AB  - Continuous hemofiltration is used widely in the management of patients with acute
      renal failure, but administration guidelines for many drugs have yet to be
      established. In this study, the pharmacokinetics of ceftriaxone were compared in
      patients with normal renal function (n = 9), mild renal insufficiency (n = 5),
      and acute renal failure receiving continuous veno-venous hemofiltration (n = 6).
      Pharmacokinetic parameters were determined under steady state conditions.
      Patients with mild renal insufficiency had a significantly lower renal clearance
      and longer half-life of ceftriaxone; however, drug recovery in the ultrafiltrate
      with continuous veno-venous hemofiltration was similar to that in the urine of
      patients with normal renal function. Pharmacokinetic parameters for renal,
      nonrenal, and systemic clearance and for volume of distribution and half-life
      were also similar between patients receiving continuous veno-venous
      hemofiltration and those with normal renal function. The sieving coefficient (S)
      of ceftriaxone (0.69) significantly exceeded the expected free fraction in
      plasma, confirming previous reports that protein binding does not limit the
      sieving of this compound. The results suggest that a reduction in the usual daily
      dose of ceftriaxone is not required in patients with acute renal failure
      receiving continuous veno-venous hemofiltration.

PMID- 9013366
TI  - Pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating
      factor: the effects of zidovudine.
AB  - Recombinant human granulocyte-macrophage colony-stimulating factor (rHu GM-CSF)
      enhances bone marrow production of and stimulates granulocytes, macrophages, and
      eosinophils. Granulocyte-macrophage colony-stimulating factor may be used
      concomitantly with zidovudine in human immunodeficiency virus (HIV)-positive
      patients to minimize zidovudine-associated neutropenia. This open-label,
      randomized, placebo-controlled study was performed to evaluate the
      pharmacokinetic disposition of rHu GM-CSF in HIV-positive, asymptomatic patients
      in the absence and presence of concomitant zidovudine administration. Eight
      participants received rHu GM-CSF (5 micrograms/kg subcutaneously) daily for 4
      days in combination with placebo or zidovudine (200 mg orally every 8 hours) in a
      randomized, crossover fashion, with each study period separated by a 3-day
      washout phase. Pharmacokinetic blood sampling was performed over 16 hours on days
      1 and 4 of both treatment periods, and subsequent analysis of serum was performed
      using an enzyme-linked immunosorbent assay. Pharmacokinetic results of rHu GM-CSF
      at steady state (days 4 of periods I and II) in the absence (placebo) and
      presence of zidovudine included apparent total body clearance, half-life, and
      apparent volume of distribution, all of which were not significantly altered with
      concomitant administration of zidovudine. Mean pharmacokinetic results of rHu GM
      CSF after the first dose (days 1 of periods I and II) were similar to steady
      state values; however, total body clearance was significantly increased at steady
      state compared with the results of the first dose. Concurrent administration of
      zidovudine does not influence the pharmacokinetic disposition of rHu GM-CSF after
      single or multiple doses.

PMID- 9013370
TI  - Cardiovascular effects of anabolic steroids in weight-trained subjects.
AB  - The effects of large doses of anabolic steroids on 24-hour blood pressure,
      cardiac structure and function, and lipid profiles were studied in 10 body
      builders using anabolic steroids and 14 body builders who did not use steroids
      (control subjects). All subjects underwent noninvasive 24-hour blood pressure
      monitoring, echocardiography, Doppler analysis of transmitral flow, and analysis
      for lipoprotein and gonadotropin levels. Anabolic steroid users were studied at
      the end of a steroid cycle and after a period of withdrawal. Average 24-hour
      blood pressure was similar in the two groups, but anabolic steroid users
      exhibited a smaller pressure reduction during sleep than did nonusers. This
      finding was present both at the end of treatment and after the period of
      withdrawal. Echocardiographic dimensional and functional indexes did not differ
      substantially between anabolic steroid users and the nonusers, and were similar
      in anabolic steroid users during use and after withdrawal. Anabolic steroid users
      also had higher LDL and lower HDL cholesterol levels than nonusers; Lp(a) was
      higher in nonusers, although this difference did not attain the level of
      statistical significance. These differences were more striking at the end of the
      treatment period. The results of this study show that chronic anabolic steroid
      intake causes an abnormal 24-hour blood pressure pattern, characterized by a
      flattening of the diurnal curve, and minor changes of the dimensional
      echocardiographic parameters.

PMID- 9013371
TI  - Effects of angiotensin-converting enzyme inhibition on left ventricular geometric
      patterns in patients with essential hypertension.
AB  - Although angiotensin-converting enzyme inhibitors have been shown to affect left
      ventricular (LV) remodeling favorably in several conditions, it remains unclear
      whether they can influence LV geometric pattern in hypertension. To address this
      issue, 122 patients (71 men and 51 women; mean age = 51 +/- 10 years) with mild
      to moderate hypertension were studied prospectively. All underwent clinical
      evaluation and Doppler echocardiography at entry and more than 2 years of
      quinapril therapy (10-40 mg/day). According to either LV mass (normal if < 131
      g/m2 for men or < 100 g/m2 for women) or the ratio of LV posterior wall thickness
      to diastolic diameter (RWT; normal if < 0.45) at baseline, 58 patients had normal
      mass and RWT, 18 patients had concentric remodelling (i.e., normal mass but
      increased RWT), 24 patients had eccentric hypertrophy (i.e., increased mass but
      normal RWT), and 22 patients had concentric hypertrophy (i.e., increase in both
      mass and RWT). After 6 months of quinapril therapy, all patients with normal left
      ventricles showed the maintenance of mass and RWT within normal limits. Patients
      with concentric remodeling showed no increase in mass but had a significant
      decrease in RWT. Patients with eccentric hypertrophy exhibited a significant
      reduction in mass with no substantial change in RWT. Patients with concentric
      hypertrophy had a significant reduction in both mass and RWT. Changes in LV mass
      and geometry were maintained during the 2-year period of treatment and were
      paralleled by improvements in Doppler indices of LV diastolic function in each
      group. It is concluded that quinapril, with its well-known effects on LV
      hypertrophy, modifies the LV geometric pattern of hypertensive patients
      favorably, regardless of the presence of an abnormal LV mass or RWT.

PMID- 9013369
TI  - Pharmacodynamic evaluation of codeine using tooth pulp evoked potentials.
AB  - Pain assessment in human volunteers is difficult, and it often requires a large
      number of subjects to show analgesic efficacy with statistical significance.
      Electrical tooth pulp stimulation elicits a painful sensation and produces an
      electroencephalographic (EEG) signal that can be recorded from the scalp when
      precisely controlled dental stimuli are delivered. These somatosensory evoked
      potentials (EP) consist of a series of peaks or waves each characterized by their
      polarity, latency, and amplitude. They are obtained by processing the EEG signals
      that occur after tooth pulp stimulation. There is good correlation between
      subjective pain reports and evoked potential amplitudes (N150-P250 component).
      Thus, EP may provide a useful model for the assessment of analgesic activity in
      human volunteers. We describe an improved method for producing and recording
      tooth pulp evoked potentials in six healthy subjects. Only 16 EEG epochs were
      necessary to get a reproducible EP response from the participants. The approach
      was applied to study the efficacy of codeine (60 mg administered orally); a
      decrease in the evoked potential amplitudes after codeine administration was
      observed. The data were consistent with results from visual analog pain ratings
      given by the subjects.

PMID- 9013365
TI  - Pharmacokinetics of prednisolone during administration of sirolimus in patients
      with renal transplants.
AB  - The pharmacokinetic interaction of multiple oral doses of sirolimus (rapamycin)
      and prednisone were evaluated in 40 stable patients with renal transplants
      receiving concomitant multiple doses of cyclosporine. Nine sirolimus dosage
      levels from 1 mg/m2/day to 13 mg/m2/day were studied and compared with placebo.
      Plasma concentrations of prednisone, prednisolone, and cortisol were measured by
      high-performance liquid chromatography and analyzed by noncompartmental methods.
      Mean pharmacokinetic values of prednisolone found before sirolimus administration
      were as follows: peak plasma concentration (Cmax) was 187 ng/mL; time to peak
      plasma concentration (tmax) was 2.03 hours; rate of reaching peak plasma
      concentration (Cmax divided by the area under the concentration-time curve [AUC])
      was 0.149 hour-1; terminal half-life (t1/2) was 3.60 hours; AUC was 1206
      ng.hour/mL; and apparent clearance (Cl/F) was 0.094 L/hour/kg. During the 2 weeks
      of concomitant administration, prednisolone elimination decreased in relation to
      sirolimus dosages. These changes were modest, with mean increases of 18% in Cmax
      and 27% in t1/2 and mean decreases of 27% in Cl/F for the groups receiving 6
      mg/m2/day to 13 mg/m2/day. Most patients initially had plasma cortisol
      concentrations indicative of adrenal suppression. With sirolimus treatment, the
      Cmax of cortisol did not decrease further, but the AUC (8:00 AM-8:00 PM) values
      were significantly lower, independent of sirolimus exposure. The AUC for
      cyclosporine did not correlate with sirolimus and prednisolone exposure. A 2-week
      course of sirolimus showed a slight pharmacokinetic interaction between sirolimus
      and prednisolone/prednisone/cortisol in stable patients with renal transplants.

PMID- 9013368
TI  - Nonprescription ibuprofen and acetaminophen in the treatment of tension-type
      headache.
AB  - A single-dose, double-blind, randomized clinical trial was conducted to examine
      the relative analgesic effectiveness of 400 mg of ibuprofen (n = 153), 1,000 mg
      of acetaminophen (n = 151), and placebo (n = 151) in volunteers with muscle
      contraction headache. At regular intervals during a 4-hour period, participants
      evaluated headache pain intensity on a 100-mm visual analog scale and headache
      pain relief on a six-category scale. Both active agents were significantly
      different from placebo at all time points and in reducing pain intensity and
      providing relief of headache overall. Similarly, ibuprofen at 400 mg differed
      significantly from acetaminophen at 1,000 mg on both rating scales. Participants
      receiving ibuprofen at 400 mg achieved complete relief of headache faster than
      those receiving acetaminophen at 1,000 mg or placebo, and more participants
      taking ibuprofen experienced complete relief of headache than those taking
      placebo or acetaminophen. Both ibuprofen at 400 mg and acetaminophen at 1,000 mg
      are efficacious analgesic agents for muscle contraction headache, and ibuprofen
      at 400 mg is significantly more effective than acetaminophen at 1,000 mg for
      treating this condition.

PMID- 9013372
TI  - Comparisons of oxidative metabolism and reductive capacity in sulfonamide
      tolerant and -intolerant patients with human immunodeficiency virus.
AB  - Hypersensitivity reactions to trimethoprim/sulfamethoxazole occur with a high
      frequency in human immunodeficiency virus (HIV)-infected patients. This study
      tested whether differences in oxidative metabolism and plasma reductive capacity
      correlate with sulfonamide intolerance in patients with HIV. Eighteen stable
      outpatients with HIV were prospectively studied. Nine patients had documented
      histories of hypersensitivity reactions to trimethoprim/sulfamethoxazole and nine
      did not. Urinary caffeine metabolite ratios assessed the activity of two
      oxidative enzymatic pathways: cytochrome P-450 1A2 (demethylation) and 8
      hydroxylation. Plasma cyst(e)ine was used as a measure of reductive capacity. The
      trimethoprim/sulfamethoxazole-intolerant group showed greater rates of 8
      hydroxylation, lower rates of demethylation, and lower cyst(e)ine levels. The
      results of this pilot study extend previous observations of differences in
      oxidative metabolism and reductive capacity that exist within the population of
      HIV-infected individuals. In addition, these findings lay the groundwork for
      future interventional studies that could use agents to inhibit sulfonamide
      oxidation and increase reductive capacity in sulfonamide-intolerant patients with
      HIV when rechallenged with trimethoprim/sulfamethoxazole.

PMID- 9013374
TI  - Pharmacokinetic interactions of moricizine and diltiazem in healthy volunteers.
AB  - Sixteen healthy male volunteers completed a nonrandomized, sequential, three
      phase study. The three phases were 1) moricizine at 250 mg every 8 hours for 7
      days with 12 days washout; 2) diltiazem at 60 mg every 8 hours for 7 days; and 3)
      concomitant administration of moricizine at 250 mg and diltiazem at 60 mg every 8
      hours for 7 days. The plasma concentration-time profiles were obtained at the end
      of each phase for moricizine, diltiazem (with its metabolites desacetyl-diltiazem
      and N-desmethyl-diltiazem), and both when administered together. Under steady
      state conditions, there was a two-way (opposing) pharmacokinetic drug interaction
      when moricizine and diltiazem were coadministered in healthy volunteers. Both
      maximum plasma concentration (Cmax) and the area under the plasma concentration
      time curve from time 0 to the end of administration (AUC tau) of moricizine
      increased significantly by 88.9% and 121.1%, respectively. Oral clearance (Clo)
      decreased by 54%. The terminal half-life (t1/2) of moricizine was not affected,
      however (2.1 +/- 0.5 hours versus 2.4 +/- 0.7 hours). It is believed that these
      changes were due to the inhibition of hepatic metabolism by diltiazem, which
      resulted in an increased systemic availability of moricizine. Moricizine had
      opposite effects on the pharmacokinetics of diltiazem. Moricizine decreased the
      Cmax of diltiazem significantly (by 36%) and increased Clo by 52%. A small but
      statistically significant decrease in the t1/2 from 4.6 +/- 1.3 hours to 3.6 +/-
      0.7 hours was observed. Despite this result, no remarkable changes (e.g., in
      Cmax, AUC, or t1/2) were found for the two major diltiazem metabolites desacetyl
      diltiazem and N-desmethyl-diltiazem. It appears that the pharmacokinetic
      interaction of moricizine and diltiazem was metabolic. With the increase in
      moricizine concentrations and the decrease in diltiazem concentrations,
      adjustments in dose may be required to achieve optimal therapeutic response when
      coadministering both agents.

PMID- 9013376
TI  - Understanding the chiral pharmacology of nonsteroidal antiinflammatory drugs in
      the aryl propionic acid class: S(+) ibuprofen. Overview of the symposium "update
      on S(+) ibuprofen" (Going/Kitzbuehl, Austria, February 2-4, 1996)

PMID- 9013375
TI  - Assessment of the pharmacokinetic-pharmacodynamic interaction between terazosin
      and finasteride.
AB  - The pharmacokinetic-pharmacodynamic interaction between terazosin and finasteride
      was evaluated in an 18-day, parallel, open-label, randomized study. Forty-eight
      non-smoking, healthy, adult male volunteers entered the study. One third of the
      participants received terazosin alone, one third received terazosin and
      finasteride, and one third received finasteride alone. Multiple-dose
      coadministration of terazosin and finasteride did not alter the central values of
      steady-state pharmacokinetic parameters of either drug in a statistically
      significant manner. Compared with the single-agent groups, however, the group
      taking finasteride and terazosin had higher variability in the pharmacokinetic
      parameters of both drugs. Testosterone concentrations were not altered after
      administration of finasteride and terazosin alone or in combination. Terazosin
      administered alone did not affect the dihydrotestosterone concentrations. The
      significant reduction in dihydrotestosterone concentrations induced by
      administration of finasteride was not affected by coadministration of terazosin.
      Mean changes in blood pressure and pulse rate in these normotensive volunteers
      were generally slight; therefore, concurrent administration of multiple doses of
      terazosin and finasteride did not produce significant clinical concern.

PMID- 9013373
TI  - Effect of dirithromycin on human CYP3A in vitro and on pharmacokinetics and
      pharmacodynamics of terfenadine in vivo.
AB  - Terfenadine is metabolized by the cytochrome P-450 3A subfamily of enzymes
      (CYP3A). Certain macrolide antibiotic agents inhibit CYP3A and, when
      coadministered with terfenadine, result in a drug interaction. The authors
      compared the abilities of dirithromycin (a new macrolide antibiotic agent), its
      major metabolite erythromycylamine, and the known CYP3A substrate terfenadine to
      inhibit CYP3A in vitro. The hydroxylation of midazolam in human liver microsomes
      was used as a probe for CYP3A activity. Dirithromycin and erythromycylamine were
      low affinity inhibitors of CYP3A (inhibitory binding affinities of 493 mumol/L
      and 701 mumol/L, respectively); conversely, terfenadine was a moderate affinity
      inhibitor (inhibitory binding affinity of 28 mumol/L). Based on these data, the
      authors tested the hypothesis that dirithromycin would not interact with
      terfenadine in humans. Six healthy men received terfenadine alone (60 mg twice
      daily) for 8 days, after which dirithromycin (500 mg once daily) was added to the
      terfenadine regimen for an additional 10 days. The pharmacokinetics of
      terfenadine (and its acid metabolite) and the QTc interval were measured during
      both treatments, and it was found that neither parameter was affected. In this
      study, dirithromycin was found to have low affinity for human CYP3A in vitro,
      which is in accordance with the study's finding that in vivo dirithromycin has no
      major effect on the metabolism of the CYP3A substrate terfenadine in humans.

PMID- 9013377
TI  - Physical aspects of dexibuprofen and racemic ibuprofen.
AB  - This article presents a comparative study of ibuprofen materials in their solid
      state. Ibuprofen crystallizes into two different structures for the S(+)
      enantiomer (dexibuprofen) and racemic ibuprofen. The crystal structure of
      ibuprofen, its optical absorption and photoluminescence, and the thermodynamic
      results (melting point and heat of fusion) are discussed. From these
      physicochemical properties, the authors conclude that dexibuprofen, which is the
      most active species pharmaceutically, and racemic ibuprofen are inherently
      different solid-state materials.

PMID- 9013378
TI  - Pharmacodynamics and pharmacokinetics of the profens: enantioselectivity,
      clinical implications, and special reference to S(+)-ibuprofen.
AB  - The 2-arylpropionic acid derivatives, or "profens," are an important class of
      nonsteroidal antiinflammatory drugs (NSAIDs) that have been in clinical use for
      almost 30 years. Widely used members of this drug class include naproxen,
      ibuprofen, ketoprofen, flurbiprofen, and tiaprofenic acid. With the exception of
      S-naproxen, the profens have until recently been used clinically as racemic
      agents, and a "single enantiomer versus racemate" debate has emerged. Several
      important issues should be considered in the debate: the antinociceptive activity
      of the R-enantiomer of at least one profen (flurbiprofen), the possible role of
      cyclooxygenase (COX)-independent properties of the R-enantiomers in the
      gastrointestinal toxicity of the racemates, the increase in the formation of
      potentially immunogenic drug-protein adducts when racemates are administered, and
      the likelihood that the use of racemates increases the propensity of the profens
      to alter the pharmacokinetics of other drugs. This review will demonstrate how
      the use of individual enantiomers can improve understanding of the mechanisms by
      which the profens elicit their biologic effects.

PMID- 9013379
TI  - Inhibition of cyclooxygenase-1 and -2 by R(-)- and S(+)-ibuprofen.
AB  - Since the discovery of a cytokine-inducible isozyme of cyclooxygenase (COX-2),
      its pharmacologic inhibition has been the subject of recent investigations. These
      include tests for the selectivity of known nonsteroidal antiinflammatory drugs
      (NSAIDs) on the constitutive enzyme of cyclooxygenase (COX-1) compared with the
      inducible enzyme COX-2. The interesting question arose whether the R(-)- and S(+)
      isomers exhibited different inhibitory potencies for ibuprofen. Results with
      isolated COX-1 and COX-2 isozymes confirmed the known higher efficacy of S(+)
      compared with R(-)-ibuprofen. The R(-)-isomer is almost inactive in inhibiting
      COX-2. In addition, the S(+) form has a several times lower potency with COX-2
      than with COX-1. These data were evaluated in platelets containing mainly the
      constitutive COX-1, with interleukin-1, pretreated, rat mesangial cells which
      almost exclusively express COX-2.

PMID- 9013380
TI  - Nonsteroidal antiinflammatory drug modulation of behavioral responses to
      intrathecal N-methyl-D-aspartate, but not to substance P and amino-methyl
      isoxazole-propionic acid in the rat.
AB  - Antinociception by nonsteroidal antiinflammatory drugs, notably diclofenac and
      S(+)-ibuprofen, has traditionally been attributed to peripheral tissue
      cyclooxygenase inhibition. This study investigates the potential role of the
      nitric oxide system for the central antinociceptive effects of diclofenac, S(+)-,
      and R(-)-ibuprofen. Diclofenac and S(+)- but not R(-)-ibuprofen inhibited the
      behavioral response dose dependently, "biting, scratching, and licking (BSL),"
      induced by the spinal application of N-methyl-D-aspartate, but not that of amino
      methylisoxazole-propionic acid or substance P. Diclofenac and S(+)-ibuprofen
      induced a parallel shift in the number of BSL responses and in the duration of
      the response in the behavioral model at their approximate median effective doses
      (diclofenac 1 mumol and S(+)-ibuprofen 5 mumol). Pretreatment with L-arginine,
      the natural substrate for the nitric oxide synthetase, antagonized diclofenac,
      and S(+)-ibuprofen-induced suppression of the biting, scratching, and licking
      response evoked by intrathecal N-methyl-D-aspartate. D-arginine did not
      antagonize the diclofenac- and S(+)-ibuprofen-induced antinociception. The study
      results indicate that analgesia after diclofenac and S(+)-ibuprofen involves a
      central mechanism which may add to the peripheral antinociceptive effect of these
      agents. The central action of diclofenac and S(+)-ibuprofen is partly mediated by
      an interaction with the N-methyl-D-aspartate receptor and nitric oxide-generating
      mechanisms.

PMID- 9013381
TI  - Ibuprofen enantiomers and lipid metabolism.
AB  - Recent findings concerning the mechanism of the chiral inversion of "profens"
      have given a better understanding of the ways in which profens interact with
      lipid biochemistry. This study presents investigations and findings concerning
      the influence of coenzyme-A (CoA) levels on the chiral inversion of ibuprofen.
      Measurement of intracellular coenzyme-A levels in isolated rat hepatocytes
      revealed that R-ibuprofen transiently reduced coenzyme-A levels, whereas S
      ibuprofen had no effect. Other experiments were performed with rat hepatocyte
      suspensions, including tests with various concentrations of clofibric acid added
      to incubates. Results showed that both clofibric acid pretreatment and its
      presence in the perfusion medium increases the chiral inversion of R-ibuprofen.
      These results confirm a metabolic interaction between ibuprofen and clofibric
      acid. Clinical studies are continuing to determine whether this metabolic
      interaction has toxicologic consequences.

PMID- 9013382
TI  - Reevaluation of some double-blind, randomized studies of dexibuprofen (Seractil):
      a state-of-the-art overview. Studies in patients with lumbar vertebral column
      syndrome, rheumatoid arthritis, distortion of the ankle joint, gonarthrosis,
      ankylosing spondylitis, and activated coxarthrosis.
AB  - This article presents a reevaluation of studies previously performed regarding
      the efficacy and safety of dexibuprofen (Seractil; S(+)-ibuprofen) for use in
      patients with inflammatory or degenerative diseases. Using appropriate
      standardized measures (univariate and multivariate analysis with the Mann-Whitney
      statistic with confidence intervals), the authors were able to compare the
      effects of treatment in different diseases. For the primary criterion and for the
      combined analysis of all efficacy criteria, one-sided equivalence was proved in
      all six studies reviewed.

PMID- 9013383
TI  - Antagonism of NMDA receptors but not AMPA/kainate receptors blocks bursting in
      dopaminergic neurons induced by electrical stimulation of the prefrontal cortex.
AB  - Evidence suggests that the prefrontal cortex (PFC) plays an important role in the
      burst activity of midbrain dopaminergic (DA) neurons. In particular, electrical
      stimulation of the PFC elicits patterns of activity in DA neurons, closely time
      locked to the stimulation, which resemble natural bursts. Given that natural
      bursts are produced by the activity of excitatory amino acid (EAA)-ergic
      afferents, if PFC-induced time-locked bursts are homologues of natural bursts,
      EAA antagonists should attenuate them. Hence, the NMDA (N-methyl-D-aspartate)
      antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) and
      the AMPA (D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid)/kainate
      antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) were applied by
      iontophoresis to DA neurons exhibiting time-locked bursts during PFC stimulation.
      CPP produced a significant reduction in time-locked bursting. In contrast, CNQX
      (at currents which antagonised AMPA responses) did not. These effects of CPP and
      CNQX on time-locked bursting mirror the effects previously reported for these
      drugs on natural bursting. Since natural bursting and bursting induced by PFC
      stimulation are both blocked selectively by CPP, the present results increase the
      degree of analogy between the two burst phenomena, thereby adding extra support
      to the contention that the cortex is involved in producing the natural bursting
      in DA neurons.

PMID- 9013384
TI  - Selective protection against AMPA- and kainate-evoked neurotoxicity by
      (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahyd roisoquinoline- 3
      carboxylic acid (LY293558) and its racemate (LY215490).
AB  - Glutamate receptor-mediated excitotoxicity is linked to the activation of
      multiple receptors including those activated by alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA), N-methyl-D-aspartate (NMDA), and kainate. In
      this study, the novel glutamate receptor antagonist, as its active isomer
      (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]-decahyd roisoquinoline-3-
      carboxylic acid ((-)LY293558) and it's +/- racemate (LY215490), was examined for
      neuroprotectant effects against excitotoxic injury in vitro and in vivo. This
      agent selectively protected against AMPA and kainate injury in cultured primary
      rat hippocampal neurons, an in vivo rat striatal neurotoxicity model, and against
      agonist-evoked seizures in mice. Thus, (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5
      yl)ethyl]decahydr -oisguino-line-3-carboxylic acid represents a novel receptor
      selective and potent systemically active AMPA/kainate receptor antagonist for
      exploring neuroprotection via non-NMDA receptor mechanisms.

PMID- 9013385
TI  - Changes of inhibitory interneurons during transcallosal stimulations.
AB  - The present study was performed in order to determine the influence of
      ipsilateral transcranial magnetic stimulations (TMS) on the silent period evoked
      by contralateral cortical stimulations. Ipsilateral TMS preceded the
      contralateral magnetic or electrical cortex stimulation by 0-50 ms. In all
      subjects, the duration of the silent period was decreased in interstimulus
      intervals of 20-30 ms when using magnetic ipsi- and contralateral stimuli. No
      change in the silent period was seen with ipsilateral magnetic and contralateral
      electrical stimulations. Decreases of motor evoked potential amplitudes were an
      inconsistent phenomenon. The results indicate that ipsilateral TMS in activate
      inhibitory cortical interneurons, probably via transcallosal pathways. Different
      time courses and different degrees of inhibition indicate that motor excitation
      and inhibition may be mediated by different neuronal circuits.

PMID- 9013386
TI  - Interactions between dopamine and GABA in the control of ambulatory activity.
AB  - Ambulatory activity of male rats was quantified in an open field. The subjects
      were treated with DL-amphetamine and amfonelic acid alone or combined with the
      GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate as
      well as with the GABAA agonist THIP and the GABAB agonist baclofen. Subeffective
      doses of the GABAergic drugs did not modify the effects of moderate doses of the
      dopaminergic stimulants whereas effective doses continued to reduce ambulatory
      activity just as in the absence of dopaminergic activation. When DL-amphetamine
      or amfonelic acid were administered in doses that strongly enhanced ambulatory
      activity, doses of the GABAergic drugs that were inhibitory in the absence of
      dopaminergic stimulation were no longer effective. The mixed D1/D2 dopamine
      antagonist pimozide, the D1 antagonist SCH 23390 and the D2 antagonist sulpiride
      were then combined with subeffective doses of the GABA agonists. GAG, sodium
      valproate and baclofen were potentiated by pimozide and SCH 23390 but not by
      sulpiride. THIP was ineffective. These data show that GABAergic drugs had a
      reduced effect after stimulation of dopaminergic neurotransmission. On the other
      hand, when dopamine D1 receptors were blocked, nonselective GABA agonists and the
      GABAB agonist baclofen were potentiated. This was not the case for the GABAA
      agonist THIP, suggesting that the GABAA receptor is of slight importance for the
      interactions between GABA and dopamine in the control of ambulatory activity. No
      potentiation of GABAergic agonists was obtained after treatment with a dopamine
      D2 antagonist.

PMID- 9013387
TI  - Taurine infused intrastriatally elevates, but intranigrally decreases striatal
      extracellular dopamine concentration in anaesthetised rats.
AB  - In the present study we infused taurine (50, 150 or 450 mM, 2 microliters/min for
      4h) into the dorsal striatum or into the substantia nigra via microdialysis probe
      and estimated the extracellular concentrations of dopamine and its metabolites,
      3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the dorsal
      striatum of anaesthetised rats. Intrastriatal infusion of taurine elevated
      striatal dopamine at all concentrations studied. At the 450 mM concentration
      taurine elevated the extracellular dopamine 10-fold, but only in the first 30 min
      sample after starting the taurine infusion. At 50 and 150 mM taurine elevated
      dopamine throughout the 4h infusion maximally up to 3-4-fold the control level.
      Extracellular DOPAC was increased by 150 and 450 mM taurine (up to about 150-160%
      of the control level), whereas at all three concentrations taurine decreased HVA
      to about 85% of the control; however, the decrease caused by 450 mM taurine was
      short-lasting. At all three concentrations taurine infused into the substantia
      nigra decreased the extracellular dopamine in the ipsilateral striatum to about
      40-50% of the control, and increased extracellular DOPAC and HVA maximally to
      about 150% and 170% of the control, respectively. These results show that the
      effects of taurine on the concentrations of extracellular dopamine and its
      metabolites depend on its administration site on nigrostriatal dopaminergic
      neurons. It elevates the extracellular dopamine when given into the striatum, but
      when given into the cell body region of the nigrostriatal dopaminergic pathway it
      decreases the extracellular dopamine in the ipsilateral striatum.

PMID- 9013388
TI  - Effect of interferon-alpha on DOI-induced wet-dog shakes in rats.
AB  - Acute (1 h) intraperitoneal (i.p.) treatment with interferon (IFN)-alpha-2a (300
      IU/g) significantly inhibited wet-dog shakes (WDS) induced by (+/-)-1-(2,5
      dimethoxy-4-iodophenyl)-2 aminopropane (DOI; 0.5, 1.0 mg/kg), which is mediated
      by serotonin (5-hydroxytryptamine; 5-HT)2 receptor in rats. IFN-alpha did not
      affect spontaneous locomotion. The inhibition of DOI (0.5 mg/kg)-induced WDS by
      IFN-alpha was dose (90-300 IU/g)- and time (1-6 h)-dependent, and was prevented
      by 30 min pretreatment with naltrexone (NLTX; 1.0 mg/kg, i.p.), an opioid
      receptor antagonist. Acute (1 h) intracerebroventricular (i.c.v.) treatment with
      IFN-alpha (1,500 IU/rat) also inhibited DOI (0.5 mg/kg)-induced WDS, and the
      effect was blocked by NLTX (50 micrograms/rat, i.c.v.). These results suggest
      that IFN-alpha may modulate 5-HT2 receptor-mediated behavior through opioid
      receptors in the central nervous system.

PMID- 9013389
TI  - Identification of serotonin transporter mRNA in rat platelets.
AB  - Total RNA isolated from rat platelets by guanidinium-acid-phenol extraction, and
      mRNA for the serotonin (5-hydroxytryptamine) transporter (5HTt) was identified.
      From a typical starting sample of 20 mL of rat blood (approximately 9 x 10(9)
      platelets), 14 to 17 micrograms of total platelet RNA was obtained. Northern blot
      analysis, using 32P-labeled 5HTt cDNA as a probe, identified approximately 3.3 kb
      long 5HTt mRNA. After rehybridization with cyclophilin cDNA, approximately 1 kb
      long mRNA for cyclophilin, which could serve as a reference for 5HTt mRNA
      quantification, was also identified. Densitometric analysis demonstrated clearly
      measurable signals for both mRNAs. The possibility of quantification of rat
      platelet 5HTt mRNA should enable parallel studies on 5HTt gene expression in
      platelets and brain of the same animal, and the evaluation of the platelet model
      at the molecular genetic level.

PMID- 9013390
TI  - Neuropharmacological characterization of local ibogaine effects on dopamine
      release.
AB  - Local perfusion with ibogaine (10(-6) M-10(-3) M) via microdialysis probes in the
      nucleus accumbens or striatum of rats produced a biphasic dose-response effect on
      extracellular dopamine levels. Lower doses (10(-6) M-10(-4) M) produced a
      decrease while higher doses (5 x 10(-4) M-10(-3) M) produced an increase in
      dopamine levels. Dihydroxyphenylacetic acid (DOPAC) levels were not effected.
      Naloxone (10(-6) M) and norbinaltorphimine (10(-6) M-10(-5) M) did not affect
      dopamine levels, but when co-administered with ibogaine (10(-4) M) blocked the
      decrease in dopamine levels produced by ibogaine. Ibogaine (10(-3) M) stimulation
      of dopamine levels in the striatum was calcium independent and not blocked by
      tetrodotoxin (10(-5) M). Pretreatment with cocaine (15 mg/kg), reserpine (5
      mg/kg) or alpha-methyl-para-tyrosine (250 mg/kg) given intraperitoneally
      significantly reduced ibogaine (10(-3)M) stimulation of striatal dopamine levels.
      In striatal synaptosomes, both ibogaine and harmaline (10(-7)-10(-4) M) produced
      dose-dependent inhibition of [3H]-dopamine uptake. These findings suggest that
      ibogaine has both inhibitory and stimulatory effects on dopamine release at the
      level of the nerve terminal. It is suggested that the inhibitory effect is
      mediated by kappa opiate receptors while the stimulatory effect is mediated by
      interaction with the dopamine uptake transporter.

PMID- 9013392
TI  - Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human
      brain: a post mortem in situ hybridization study with special reference to
      Parkinson's disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic
      factor for dopaminergic neurons. Since dopaminergic neurons degenerate in
      Parkinson's disease, this factor is a potential therapeutical tool that may save
      dopaminergic neurons during the pathological process. Moreover, a reduced GDNF
      expression may be involved in the pathophysiology of the disease. In this study,
      we tested whether altered GDNF production may participate in the mechanism of
      cell death in this disease. GDNF gene expression was analyzed by in situ
      hybridization using riboprobes corresponding to a sequence of the exon 2 human
      GDNF gene. Experiments were performed on tissue sections of the mesencephalon and
      the striatum from 8 patients with Parkinson's disease and 6 control subjects
      matched for age at death and for post mortem delay. No labelling was observed in
      either group of patients. This absence of detectable expression could not be
      attributed to methodological problems as a positive staining was observed using
      the same probes for sections of astroglioma biopsies from human adults and for
      sections of a newborn infant brain obtained at post-mortem. These data suggest
      that GDNF is probably expressed at a very low level in the adult human brain and
      its involvement in the pathophysiology of Parkinson's disease remains to be
      demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's
      disease, however.

PMID- 9013393
TI  - Simultaneously evoked primary and cognitive visual evoked potentials distinguish
      younger and older patients with Parkinson's disease.
AB  - While it is known that both primary visual processes and visuocognitive responses
      are affected in Parkinson's Disease (PD), their relationship is not known. It is
      known that both of these measures can be affected by age per se. Our aims were to
      determine if in non-demented PD patients visual cognitive event-related potential
      (ERP) changes simply reflect abnormal primary visual processing and to determine
      the effects of age and disease on their relationship. In order to do so, we
      introduce a new normalizing procedure for visual ERPs. In addition to the
      latencies and amplitudes of P100, N140, P200, N200 and P300 components, the P300
      P100 latency difference (termed "central processing time"-CPT) were measured. In
      order to avoid confounding factors of absolute amplitude differences due to say,
      generally low voltage recordings or poor primary visual responses, P300 responses
      normalized to P100 responses were also evaluated (P300/P100 amplitude ratio).
      Visual ERPs were obtained in an "oddball" paradigm in 20 nondemented patients
      with PD and 20 normal age-matched subjects. The stimuli were horizontal
      sinusoidal gratings differing only in spatial frequency (0.5 and 1 cycle/degree).
      While simple ERP latency criteria did not distinguish non-demented PD patients as
      a group from controls, when younger PD patients were compared to older PD
      patients and controls CPT acceleratedly increased in younger PD patients. The
      amplitudes of both N200 and P300 provided significant distinction between patient
      and control groups. The surprising result emerging from this study is that an
      individually normalized P300 amplitude provides significant distinction of
      younger PD patients from age matched normals.

PMID- 9013394
TI  - Stereospecific occurrence of a parkinsonism-inducing catechol isoquinoline, N
      methyl(R)salsolinol, in the human intraventricular fluid.
AB  - N-Methyl(R)salsolinol, an endogenous neurotoxin, has been proposed to be closely
      involved in the pathogenesis of Parkinson's disease. The selective toxicity to
      dopaminergic neurons was strictly limited for (R)-enantiomer of N
      methylsalsolinol. Its precursor, (R)salsolinol was enzymatically synthesized from
      dopamine and acetaldehyde in human. However, it has never been examined whether a
      non-enzymatic reaction produces racemic salsolinol derivatives from dopamine
      especially in patients under L-DOPA therapy. To clarify the point, their contents
      were examined in intraventricular fluid from parkinsonian patients administrated
      with L-DOPA. Only (R)-enantiomer of N-methylsalsolinol and very low concentration
      of salsolinol could be detected. The results suggest that N-methyl(R)salsolinol
      synthesis may not depend on dopamine level, but on the activity of enzymes
      related to its synthesis and/or catabolism. The results are discussed in relation
      to pathogenesis Parkinson's disease.

PMID- 9013395
TI  - Interleukin-2 but not basic fibroblast growth factor is elevated in parkinsonian
      brain. Short communication.
AB  - The contents of interleukin (IL)-2 and basic fibroblast growth factor (bFGF) were
      measured in the brain (caudate nucleus, putamen, and cerebral cortex) from
      control and parkinsonian patients by highly sensitive enzyme-linked immunosorbent
      assay (ELISA). The concentrations of IL-2 in the brain were in the order of pg/mg
      protein, and the values were significantly higher in the caudate and putamen from
      parkinsonian patients than those from control patients. However, the levels of IL
      2 in the cerebral cortex showed no significant difference between parkinsonian
      and control patients. In contrast to IL-2, the bFGF levels in the brain were high
      and in the order of ng/mg protein, and there was no significant difference in the
      caudate and putamen between parkinsonian and control patients. Although both IL-2
      and bFGF may play important roles in dopaminergic neurons as neurotrophic
      factors, IL-2 but not bFGF may relate to the compensatory response in the
      nigrostriatal dopaminergic regions in parkinsonian brain during progress of
      neurodegeneration.

PMID- 9013391
TI  - Animal models of Parkinson's disease: an empirical comparison with the
      phenomenology of the disease in man.
AB  - Animal models are an important aid in experimental medical science because they
      enable one to study the pathogenetic mechanisms and the therapeutic principles of
      treating the functional disturbances (symptoms) of human diseases. Once the
      causative mechanism is understood, animal models are also helpful in the
      development of therapeutic approaches exploiting this understanding. On the basis
      of experimental and clinical findings. Parkinson's disease (PD) became the first
      neurological disease to be treated palliatively by neurotransmitter replacement
      therapy. The pathological hallmark of PD is a specific degeneration of nigral and
      other pigmented brainstem nuclei, with a characteristic inclusion, the Lewy body,
      in remaining nerve cells. There is now a lot of evidence that degeneration of the
      dopaminergic nigral neurones and the resulting striatal dopamine-deficiency
      syndrome are responsible for its classic motor symptoms akinesia and
      bradykinesia. PD is one of many human diseases which do not appear to have
      spontaneously arisen in animals. The characteristic features of the disease can
      however be more or less faithfully imitated in animals through the administration
      of various neurotoxic agents and drugs disturbing the dopaminergic
      neurotransmission. The cause of chronic nigral cell death in PD and the
      underlying mechanisms remain elusive. The partial elucidation of the processes
      underlie the selective action of neurotoxic substances such as 6-hydroxydopamine
      (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has however
      revealed possible molecular mechanisms that give rise to neuronal death.
      Accordingly, hypotheses concerning the mechanisms of these neurotoxines have been
      related to the pathogenesis of nigral cell death in PD. The present contribution
      starts out by describing some of the clinical, pathological and neurochemical
      phenomena of PD. The currently most important animal models (e.g. the reserpine
      model, neuroleptic-induced catalepsy, tremor models, experimentally-induced
      degeneration of nigrostriatal dopaminergic neurons with 6-OHDA, methamphetamine,
      MPTP, MPP+, tetrahydroisoquinolines, beta-carbolines, and iron) critically
      reviewed next, and are compared with the characteristic features of the disease
      in man.

PMID- 9013397
TI  - Dopamine D2 receptor binding is reduced in Wilson's disease: correlation of
      neurological deficits with striatal 123I-iodobenzamide binding.
AB  - To visualise and quantify dopamine D2 receptor binding in the corpus striatum of
      patients with neurological Wilson's disease (WD) 123I-Iodobenzamide (IBZM)
      binding was measured using single photon emission computer tomography (SPECT).
      Ratios of striatal to frontal countrates were calculated in 8 patients and in 21
      healthy control subjects. We found reduced IBZM binding ratios in all patients
      with WD in comparison to those in controls (1.48 +/- 0.13 vs. 1.73 +/- 0.09). The
      reduction in IBZM binding was correlated with the overall severity of
      neurological deficits and the severity of dysarthria (correlation coefficients 
      0.86 [p < 0.01] and -0.79 [p < 0.01], respectively). When patients of three
      different subgroups of neurological WD were compared no differences in IBZM
      binding were found. We conclude that assessing basal ganglia function in vivo
      using IBZM-SPECT is a valuable diagnostic tool in WD.

PMID- 9013396
TI  - Neurotransmitters in CSF of idiopathic adult-onset dystonia: reduced 5-HIAA
      levels as evidence of impaired serotonergic metabolism.
AB  - While several radiological findings point towards the basal ganglia as a possible
      anatomical site of the lesion in dystonia patients the biochemical basis of the
      disorder is still unknown. 5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic
      acid (HVA) levels-the respective metabolites of serotonin and dopamine-were
      measured in lumbar cerebrospinal fluid (lCSF) of 15 patients with idiopathic
      adult-onset focal dystonia and in lCSF of 11 controls. 100 microliters lCSF were
      analyzed for 5-HIAA and HVA by reversed-phase HPLC with electrochemical
      detection. 5-HIAA levels were significantly reduced in dystonia patients (11.4
      micrograms/ml) compared to controls (18.4 ng/ml) (p < 0.02). HVA levels in
      dystonia patients (30.3 ng/ml) were below control values (41.6 ng/ml) but this
      finding did not reach statistical significance. Decreased lCSF levels of 5-HIAA
      suggest an impaired serotonin metabolism in patients with idiopathic adult-onset
      dystonia. This observation may provide a biochemical basis for a more specific
      pharmacotherapy in dystonia patients.

PMID- 9013398
TI  - Velnacrine for the treatment of Alzheimer's disease: a double-blind, placebo
      controlled trial. The Mentane Study Group.
AB  - The present study examines the safety and efficacy of the centrally acting
      cholinesterase inhibitor, velnacrine, in treating the cognitive symptoms of
      Alzheimer's disease. Seven hundred thirty-five patients with mild-to-severe
      Alzheimer's disease were treated in a double-blind, placebo-controlled study.
      Following the screen visit, patients were treated with velnacrine (10, 25, 50 and
      75 mg t.i.d.) or placebo in a double-blind dose-ranging study to identify
      velnacrine-responsive patients and their best dose. Following placebo washout
      velnacrine responsive patients were randomly assigned to their best dose of
      velnacrine (N = 153) or placebo (N = 156) in a six week double-blind dose
      replication study. Primary efficacy measures were the cognitive subscale of the
      Alzheimer's Disease Assessment Scale (ADAS) and the Physician's Clinical Global
      Impression of Change. Statistically significant improvement was observed in both
      primary efficacy measures in velnacrine-treated patients during the dose
      replication study. Velnacrine patients scored better on the cognitive subscale of
      the ADAS than placebo patients (P < 0.001), with patients receiving the highest
      velnacrine dose averaging a 4.1-point improvement with respect to screen values.
      Clinical Global Impression of Change scores of velnacrine-treated patients were
      significantly improved at the end of the 6 weeks of treatment when compared to
      those of placebo patients (P < 0.05). The most common side effect was
      asymptomatic elevation in liver transaminase levels, which occurred among 29% of
      patients. These data suggest that velnacrine produces modest clinical improvement
      in a subset of patients with mild-to-severe Alzheimer's disease.

PMID- 9013399
TI  - Alpha-helical CRF blocks differential influence of corticotropin releasing factor
      (CRF) on appetitive and aversive memory retrieval in rats.
AB  - This study examined whether corticotropin releasing factor (CRF), given prior to
      test, would produce an improved retrieval of aversive memory in the same way as
      pre-exposure to inescapable footshocks and the CRF antagonist, alpha-helical CRF
      9-41 (a-h CRF), blocks this effect in rats. For this purpose animals conditioned
      in a T-maze with appetitive (10% sucrose) and aversive (2.0mA footshock) events
      were given intracerebroventricularly (i.c.v.) 20 min before testing, a single
      dose of 0.05, 0.1, 0.2 or 0.4 microgram/rat of CRF, or 5 micrograms/rat of a-h
      CRF, or both at 10 min interval. In the retention test conducted with the same
      training apparatus 72-hr after conditioning, CRF (0.05, 0.1 and 0.2 microgram)
      treated rats showed a dose-dependent increase in latencies to enter the
      previously shocked goalarm, with the absence of such a difference in responding
      to the nonshocked goalarm. The highest dose of CRF (0.4 microgram), however,
      increased the latencies to enter both the goalboxes. Alpha-helical CRF,
      administered 10 min before, antagonized the memory-enhancing effect of CRF.
      Further, CRF (0.1, 0.2 and 0.4 microgram) significantly decreased the total
      number of center entries in the open field, consistent with the view that i.c.v.
      administered CRF produces "anxiogenic-like" effect. Alpha-helical CRF reversed
      this effect. The effect of CRF on memory retrieval was similar to that seen
      following inescapable footshock in rats. The results thus suggest the possible
      involvement of central CRF mechanisms in the differential enhancement of memory
      of helplessness condition.

PMID- 9013400
TI  - Changes in EEG order in neuroleptically treated normal volunteers during a
      voluntary movement task.
AB  - 15 normal volunteers were treated over three weeks with haloperidol (HAL) and in
      the third week additionally with biperidene (BIP). The order of the EEG spectra
      at different topographical locations and in different frequency bands during a
      movement task was analyzed using uncertainty analysis (UA), a multivariate
      analysis technique based on information-theoretical methods. Different patterns
      of drug-induced changes were found. HAL decreases the theta and alpha band order
      at the fronto-central lateral areas but increases it at the fronto-central
      midline in the theta band and at the parietal areas in the alpha band. With the
      exception of the fronto-central midline locations, BIP more or less
      counterbalances the effect of HAL. Volunteers felt unwell and had motor
      disturbances during HAL and felt well again during HAL + BIP. Reaction time
      values were increased during HAL and normalized during HAL + BIP.

PMID- 9013401
TI  - NG-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure
      susceptibility in four seizure models in mice.
AB  - Nitric oxide may be involved in seizure phenomena even though data often seem to
      be contradictory. This prompted us to study the influence of nitric oxide upon
      electrically and chemically induced seizures. The effects of nitric oxide
      synthase inhibitor, NG-nitro-L-arginine (NNA), on pentylenetetrazol-,
      aminooxyacetic acid-, aminophylline-induced seizures or electroconvulsive shock
      were evaluated. NNA was applied at 1, 10 and 40 mg/ kg 0.5 and 2.0 h before
      chemical seizures and at 1 and 40 mg/kg 0.5 and 2.0 h prior to
      electroconvulsions. The nitric oxide synthase inhibitor (up to 40 mg/ kg) did not
      affect the susceptibility of mice to pentylenetetrazol, amino-oxyacetic acid or
      electroconvulsions. However, NNA significantly enhanced the convulsive properties
      of aminophylline when applied at 40 mg/kg, 0.5 h before the test. The CD50 value
      for aminophylline-induced clonus and tonus/ mortality was decreased from 233 to
      191 and from 242 to 212 mg/kg, respectively. However, this pretreatment also led
      to a significant increase in the plasma levels of theophylline. Our results
      suggest that differential effects of NNA on chemically-induced convulsions might
      in some cases be associated with a pharmacokinetic interaction.

PMID- 9013402
TI  - BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats.
AB  - To clarify clinical roles of sigma receptor binding affinity of neuroleptics,
      neck dystonia induced by microinjection of sigma receptor ligands and
      neuroleptics into rat red nucleus was investigated. DTG and (+)-3-PPP, putative
      sigma receptor agonists, induced neck dystonia in dose-dependent and reversible
      manner. Haloperidol and perphenazine induced dystonia in the same way as sigma
      receptor agonists, whereas zotepine and (-)-sulpiride did not. The rank order of
      potency in induction of dystonia and sigma receptor affinity of these compounds
      showed positive correlation. Although BMY-14802 has a high affinity for sigma
      receptors, it never produced dystonia by itself. On the other hand, combined
      injection of BMY-14802 with DTG attenuated DTG-induced dystonia. Therefore, it is
      suggested that typical neuroleptics such as haloperidol act agonistic and
      atypical neuroleptics such as BMY-14802 act antagonistic at rubral sigma
      receptors in the induction of neck dystonia.

PMID- 9013403
TI  - Antipsychotics with inverse agonist activity at the dopamine D3 receptor.
AB  - In NG 108-15 cells expressing the recombinant human D3 receptor, dopamine
      agonists enhance [3H]thymidine incorporation and decrease cAMP accumulation. In
      these cells, but not in wild type cells, haloperidol, fluphenazine, and various
      other antipsychotics inhibited basal [3H]thymidine incorporation in a
      concentration-dependent manner. In contrast, other dopamine antagonists such as
      nafadotride or (+)AJ 76, two D3-preferring antagonists, were without effect. The
      concentration-response curve of haloperidol was shifted to the right in presence
      of nafadotride, with a potency compatible with its nanomolar apparent affinity as
      neutral antagonist. Pertussis toxin treatment abolished or markedly reduced the
      responses to haloperidol or fluphenazine. In contrast, no significant enhancement
      of cAMP accumulation could be observed, under the influence of haloperidol or
      eticlopride. These data indicate that some dopamine antagonists behave as inverse
      agonists, and thus appear to inhibit an agonist-independent activity of the D3
      receptor on [3H]thymidine incorporation pathway, but not on the cAMP pathway.

PMID- 9013404
TI  - Chronic levodopa therapy enhances dopa absorption: contribution to wearing-off.
AB  - Effects of the chronic administration of levodopa on its peripheral
      pharmacokinetics and the contribution of the pharmacokinetics to the pathogenesis
      of the wearing-off phenomenon are re-evaluated. The concentration of plasma
      levodopa and clinical symptoms were determined 4 hours after oral levodopa
      (levodopa 100 mg + benserazide 25 mg) administration on 55 parkinsonian patients.
      Long-term levodopa therapy markedly increased the peak levodopa concentration
      (Cmax) and the area under the time-concentration curve (AUC); whereas, it
      decreased time to the peak concentration (Tmax) and the elimination half-life
      (T1/2). These results suggest that long-term levodopa therapy accelerates the
      absorption of levodopa. The wearing-off group (n = 23), however, had a markedly
      higher Cmax and AUC, and a shorter Tmax and T1/2 than the stable group (n = 32).
      We speculate that the clinical expression of "stable" or "wearing-off" depends on
      the absorption of levodopa as well as the presynaptic terminal and post synaptic
      receptors.

PMID- 9013405
TI  - Parenteral application of NADH in Parkinson's disease: clinical improvement
      partially due to stimulation of endogenous levodopa biosynthesis.
AB  - Exogenous application of levodopa is conventionally used to equalize the striatal
      dopamine deficit in idiopathic Parkinson's disease (PD). The stimulation of
      endogenous biosynthesis of levodopa via activation of tyrosine hydroxylase (TH)
      has been proposed as new therapeutic concept in PD. This may be achieved by
      exogenous supply with the reduced coenzyme nicotinamide adenine dinucleotide
      (NADH). Aim of this open prospective study was to investigate (1) the efficacy of
      a new developed, parenteral application form of NADH on Parkinsonian symptoms and
      (2) the influence of bioavailability of levodopa. 15 patients, suffering from
      idiopathic PD (11 male, 4 female, age: 61.40[mean] +/- 10.27[SD] range: 44-74
      years, Hoehn and Yahr stage: 3.03 +/- 0.69, range 2-4) received intravenous
      infusions of NADH (10 mg a' 30 min) over a period of 7 days in addition to
      conventional Parkinsonian pharmacotherapy. Parkinsonian symptoms were scored
      before (day 1) and after NADH treatment (day 8). Levodopa plasma levels were
      estimated over a period of four hours on the day before and on the first day of
      NADH application by HPLC. Parkinsonian patients showed a significant response,
      evaluated by the Unified Parkinson's Disease Rating Scale Version 3.0 (p = 0.025;
      Wilcoxon test). Moreover application of NADH significantly increased
      bioavailability of plasma levodopa (AUC, p = 0.035; Cmax p = 0.025). In
      conclusion NADH in used galenic form may be a potent stimulator of endogenous
      levodopa biosynthesis with clinical benefit for Parkinsonian patients.

PMID- 9013406
TI  - Visual hallucinosis: the major clinical determinant of distorted chromatic
      contour perception in Parkinson's disease.
AB  - Recently distorted chromatic contour perception has been demonstrated in
      Parkinson's disease (PD). The aim of our study is to determine the clinical
      factors which influence chromatic contour perception in PD. Chromatic and
      achromatic contour perception, colour discrimination and clinical data were
      evaluated in 73 patients with PD. We used a computer-aided method to determine
      the chromatic fusion time (CFT) which indicates the acuity of monochromatic
      contour perception. Chromatic CFT was generally shortened in patients as compared
      to controls (p < 0.01), whereas achromatic CFT was not significantly different.
      Variance analysis revealed the ability of colour discrimination and the risk of
      visual hallucinations as statistically significant (p < 0.05) variables
      influencing contour perception of certain stimuli. In contrast, disease stage,
      disease duration and disease severity have no relevant effect on chromatic
      contour perception in Parkinson's disease. On the basis of those properties one
      may suggest that distorted chromatic contour perception is due to an impairment
      at a central stage of visual processing in PD and an imbalance of the
      serotonergic system. Whether CFT is a reliable method to predict the individual
      risk of hallucinosis in PD has to be evaluated.

PMID- 9013407
TI  - Alpha 1-antichymotrypsin gene polymorphism and risk for Alzheimer's disease.
AB  - alpha 1-Antichymotrypsin (ACT), a component of the senile plaque of the
      Alzheimer's disease (AD) brain, has a possible role as a molecular chaperone in
      developing AD pathology. This study was a search for the possible association of
      the two structural polymorphisms of ACT, Ala15-->Thr and Met389-->Val in the
      Japanese population. In 101 AD patients, genotype and allele frequencies of the
      two polymorphisms did not differ from those of 104 age-matched healthy controls.
      However, in those subjects in which the apolipoprotein epsilon 4 allele was
      absent, the frequency of the Ala15 homozygote was significantly higher in the AD
      patients than in controls. This suggests that the Ala15 homozygote state may be a
      susceptibility marker for AD, interacting with apolipoprotein E genotype.

PMID- 9013408
TI  - Cerebrospinal fluid acetylcholine and choline in vascular dementia of Binswanger
      and multiple small infarct types as compared with Alzheimer-type dementia.
AB  - The acetylcholine (ACh) and choline (Ch) concentrations in the cerebrospinal
      fluid were investigated in patients with vascular dementia of the Binswanger type
      (VDBT) or multiple small infarct type (MSID) as compared with patients with
      Alzheimer-type dementia (ATD). The ACh concentration in patients with ATD was
      found to be significantly lower than in controls (73%, p < 0.0001), and showed a
      significant positive correlation with dementia scale scores (rs = 0.63, p <
      0.03). The Ch concentration in the CSF of ATD patients was approximately the same
      as in controls. In VDBT/MSID patients, the ACh concentration was significantly
      lower than in controls (p < 0.001) also showing a significant positive
      correlation with dementia scale scores (rs = 0.62, p < 0.02), but was
      significantly higher than in ATD patients (p < 0.001). Moreover, the Ch
      concentration in VDBT/MSID patients was significantly higher than in controls (p
      < 0.001) or ATD patients (p < 0.001). These results suggest that simultaneous
      determination of ACh and Ch concentrations in CSF may be useful for
      differentiating VDBT/MSID from ATD and that increasing the ACh level using
      cholinergic agents may be a beneficial therapeutic strategy for the treatment of
      ATD as well as VDBT/MSIT, and is worthy of further investigation.

PMID- 9013409
TI  - Additive effects, but no synergistic interaction of stressful life-events and
      genetic loading in affective disorders.
AB  - Life-event research as well as neurobiological findings point to the relevance of
      adverse stress for the pathogenesis of affective disorders. The well established
      genetic root might be related to the sensitivity to stress. In concordance,
      recent studies showed a synergistic interaction between genetic loading and life
      events concerning the precipitation of depression, i.e. there might exist a
      genetic sensitization to the adverse effects of stressors. The present
      investigation, using information extracted from 877 case records, did not reveal
      a synergistic interaction concerning the age at onset and the mean frequency and
      duration of episodes.

PMID- 9013411
TI  - CGP 39653 binding in the chick CNS after NMDA receptor antagonist treatment.
AB  - To analyze the affect of blocking neuronal activity on NMDA receptor levels
      during development, we have injected chick embryos with the competitive NMDA
      receptor antagonist NPC 12626 from E17 to E19. Brains from drug-treated (n = 7)
      and control (n = 6) embryos (E20) were processed for receptor autoradiography
      using the NMDA competitive antagonist [3H]CGP 39653. NPC 12626 treatment caused a
      significant 24 to 46% increase in [3H]CGP 39653 binding in both the forebrain and
      cerebellar cortex. The results support the hypothesis that NMDA receptor levels
      are regulated by activity-dependent mechanisms.

PMID- 9013410
TI  - Ontogeny of PFC-related behaviours is sensitive to a single non-invasive dose of
      methamphetamine in neonatal gerbils (Meriones unguiculatus).
AB  - A single dose of methamphetamine (50 mg/kg; i.p.) was administered to neonatal
      male gerbils (Meriones unguiculatus) aged 14 days, and adult prefrontal cortex
      (PFC)-related behaviours were analysed and compared with saline-treated controls
      at the age of postnatal day 90. For that purpose, animals were tested for open
      field activities and y-maze delayed alternation. This solitary and non-invasive
      drug challenge, which has recently been found to initiate serious restraint in
      maturation of the mesoprefrontal dopamine (DA)-system (Dawirs et al., 1994),
      induces a significant delayed alternation impairment as well as significant
      increases in open-field motor activity and emotionality. Since an undisturbed
      development of the prefrontal DA-innervation seems to be a precondition for the
      maturation of normal PFC-related behaviours, a single early methamphetamine
      impact may be a suitable animal model for further investigation of structural and
      functional aspects of non-invasively induced behavioural deficits in rodents. The
      present results are discussed with regard to the assumption that hypofunctional
      mesoprefrontal DA-systems might be basic to schizophrenic behaviours in man.

PMID- 9013412
TI  - The GABAB-receptor antagonist, CGP 35348, antagonises gamma-hydroxybutyrate- and
      baclofen-induced alterations in locomotor activity and forebrain dopamine levels
      in mice.
AB  - Previous studies have shown that administration of gamma-hydroxybutyric acid
      (GHBA) or baclofen is associated with a decrease in locomotor activity as well as
      an increase of dopamine (DA) in brain. In the present study we analyse whether
      these actions are related to activation of GABAB-receptors utilising a GABAB
      receptor antagonist, CGP 35348. Administration of GHBA (200 or 800 mg/kg, i.p.)
      or baclofen (4 or 16 mg/kg, i.p.) induced a marked and dose-dependent decrease in
      locomotor activity in mice, that was antagonised by pretreatment with CGP 35348
      (400 mg/kg, i.p.). Treatment with the highest doses of GHBA and baclofen produced
      clear-cut increases in forebrain DA concentration. Also these effects were
      effectively antagonised by pretreatment with CGP 35348. Treatment with the GABAB
      receptor antagonist alone did not influence the locomotor activity or brain DA
      concentration. These results indicate that the behaviourally depressive and DA
      increasing effects of GHBA and baclofen are mediated by activation of GABAB
      receptors.

PMID- 9013413
TI  - Histaminergic modulation of neocortical spindling and slow-wave activity in
      freely behaving rats.
AB  - Histaminergic H3 receptor antagonists stimulate neuronal histamine release and
      could consequently have a number of physiological effects in the brain. The
      effects of H3 receptor blockade, induced by systemically administered
      thioperamide, were assessed on the frontal cortex electroencephalographic (EEG)
      properties in freely behaving rats. The relationship of EEG activity variables to
      endogenous brain histaminergic markers was also examined, both in controls and in
      portocaval anastomosis (PCA)-operated rats (which show increased levels of brain
      histamine and t-methylhistamine). Thioperamide reduced the incidence of thalamus
      regulated EEG spindles, while it slightly increased their amplitude. It
      furthermore reduced the spectral power of low-frequency (1.5-5Hz) EEG, which
      effect was equally distributed over the spindle and non-spindle EEG states. These
      EEG effects were accompanied by increased motor activity of the animals. Both the
      low-frequency EEG activity and spindle incidence correlated inversely with the
      histamine level of the brain (hypothalamus and cerebellum excluded) while t
      methylhistamine level correlated with the degree of thioperamide-induced
      reduction of slow-wave EEG activity. The present results provide evidence for the
      involvement of endogenous brain histamine level, histamine release (as assessed
      by t-methylhistamine level) and H3 receptors in the histaminergic regulation of
      neocortical synchronization patterns assumed to be linked to arousal control.

PMID- 9013414
TI  - Epi-inositol is biochemically active in reversing lithium effects on cytidine
      monophosphorylphosphatidate (CMP-PA). Short communication.
AB  - In CHOm3 cells and rat cerebral cortex slices, epi-inositol was less potent but
      as effective as myo-inositol in reversing carbachol/lithium-stimulated CMP-PA
      accumulation whereas L-chiro- and scyllo-inositol were less active or inactive.
      These results with the four inositol isomers in two tissues correlate exactly
      with their effects on lithium-pilocarpine induced seizures and suggest a common
      mechanism of action for biochemical and behavioural effects.

PMID- 9013415
TI  - An in vivo comparison of the capacity of striatal versus extrastriatal brain
      regions to form dopamine from exogenously administered L-dopa.
AB  - We used the technique of cerebral microdialysis to monitor the metabolism of
      exogenously administered L-dopa and compared dopamine and dopamine metabolite
      formation in the striatum (a site containing abundant dopamine nerve terminals
      and dopa-decarboxylase (DDC) activity) versus the cerebellum and occipital cortex
      (sites with limited dopaminergic innervation and DDC activity). The
      concentrations of dopamine and the major dopamine metabolites
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in each
      brain region following L-dopa perfusion; however, dopamine formation was 90% less
      in the occipital cortex as compared to the striatum and 95% less in the
      cerebellum. DOPAC formation was 57% less in the occipital cortex and 74% less in
      the cerebellum. HVA formation was 42% less in the occipital cortex and 70% less
      in the cerebellum. The levels of the L-dopa metabolite 3-O-methyldopa and the
      serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA) were identical in the
      striatum, occipital cortex, and cerebellum both before and after L-dopa
      administration. We conclude that brain areas with marked reductions in dopamine
      nerve terminals and DDC activity have a diminished capacity to synthesize
      dopamine and also lack storage mechanisms to protect the newly synthesized
      dopamine from degradative metabolism. The relevance of these findings to the use
      of L-dopa in treating Parkinson's disease is discussed.

PMID- 9013416
TI  - L-DOPA modulation of corpus striatal dopamine and dihydroxyphenylacetic acid
      output from intact and 6-OHDA lesioned rats.
AB  - In the present report we examined the differences in in vitro dopamine (DA) and
      dihydroxyphenylacetic acid (DOPAC) efflux from the corpus striatum (CS) of intact
      versus 6-hydroxydopamine (6-OHDA) lesioned (in substantia nigra) male rats in
      response to different doses of two pulse infusions of L-dihydroxyphenylalanine (L
      DOPA). In the first experiment, we tested the effects of two 20-min infusions of
      5 uM L-DOPA. In the second experiment we repeated this protocol using 50 uM L
      DOPA. There was an overall significantly greater output of DA for intact versus 6
      OHDA lesioned rats for both doses. Moreover, in Experiment 1, the 5 uM L-DOPA
      produced a peak DA response to the second infusion which was significantly higher
      than that of the first infusion in the intact, but not lesioned rats. In
      Experiment 2, the 50 uM L-DOPA group showed no significant differences in DA
      output between the two infusions for both intact and lesioned rats. In contrast
      to DA responses, there were no overall significant differences in DOPAC output
      between intact and 6-OHDA lesioned rats for both doses. However, for both doses
      tested, the peak DOPAC output from the second infusion was significantly
      increased in lesioned, but not intact rats. These data demonstrate that L-DOPA
      evoked DA and DOPAC output are differentially modulated in intact and 6-OHDA
      lesioned striatum. The lesions of the striatal dopaminergic system may alter
      these responses through changes in intraneuronal storage and metabolism of DA
      following L-DOPA infusion.

PMID- 9013417
TI  - Combined effects of cabergoline and L-dopa on parkinsonism in MPTP-treated
      cynomolgus monkeys.
AB  - The behavioral effects of L-dopa or cabergoline alone were compared with those of
      the joint administration of the two drugs in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention
      to the induction of hyperactivity and dyskinesia. Cabergoline alone at 0.2 mg/kg
      or less improved in a dose-dependent fashion the parkinsonism without inducing
      hyperactivity and dyskinesia following a single subcutaneous injection. L-dopa
      alone improved the parkinsonism, but induced hyperactivity and dyskinesia,
      depending on the dose applied. Doses required for 50% amelioration by L-dopa and
      cabergoline were 10 and 0.038 mg/kg, s.c., respectively. With low doses (50%
      amelioration doses), cabergoline or L-dopa alone improved the parkinsonism
      without induction of hyperactivity and dyskinesia, but the duration of action was
      brief. Cabergoline in combination with L-dopa was highly effective in improving
      motor disability without induction of hyperactivity and dyskinesia. Moreover, the
      duration of action was more prolonged with the coadministration than with the
      single administration of each drug. These findings suggest that the combined
      therapy with low doses of L-dopa and cabergoline is beneficial for treating
      patients with advanced Parkinson's disease.

PMID- 9013419
TI  - Scopolamine blocks the effects of swim stress on memory retrieval in rats.
AB  - This study examined whether application of swim stress improved retrieval of a
      passive avoidance memory and if pretreatment with the anticholinergic agent,
      scopolamine, blocked this effect on memory retrieval. Animals initially given a
      passive avoidance training session were subjected to either a two or four swim
      stress sessions (15 min each) with or without prior treatment of scopolamine
      (0.05 or 0.1 mg/kg). The retrieval performance in passive avoidance test and
      motor activity was assessed 24 hr after the last swim stress session. In an
      independent control experiment, the passive avoidance training and test were
      conducted respectively, 24 and 72 hr after the last of four swim stress sessions
      with or without prior injection of scopolamine (0.1 mg/kg). The results showed an
      enhanced performance for the passive avoidance task in rats subjected to four
      swim stress sessions in both experiments and scopolamine given 30 min prior to
      each stress session diminished this performance of animals in the passive
      avoidance test. Two swim stress sessions with or without scopolamine treatment
      caused no significant effects on the retrieval performance. Also, no significant
      difference was observed among the groups in motor activity following any of the
      stress treatments in the open field test. These results, thus suggested for the
      first time, a relationship among swim stress, cholinergic activity and avoidance
      memory processes.

PMID- 9013418
TI  - Synaptophysin in spinal anterior horn in aging and ALS: an immunohistological
      study.
AB  - Aged-related spinal cord changes such as neuronal loss have been related to the
      degree of clinical severity of amyotrophic lateral sclerosis (ALS); morphological
      data on synapses are, however, wanting. Variations in synaptophysin (Sph)
      expression in aging and ALS were thus studied at the level of lower motor neurons
      in 40 controls with non-neurological diseases and 11 cases of ALS. Control
      sections of formalin fixed paraffin embedded cervical (C7/8), thoracic (T10) and
      lumbar spinal cord (L5) and C6, C7, C8 and L5 of ALS cases were stained with
      haematoxylin and eosin, luxol fast blue (LFB), and immunostained with a mouse
      monoclonal antibody against Sph. The neuropil of the anterior horn (AH) in all
      control cases demonstrated Sph positivity. A dot-like pattern of positivity of
      presynaptic terminals on soma of motor neurons and fine immunoreactivity along
      neuronal processes were observed. A significant reduction of Sph immunostaining
      was observed in the neuropil with increasing age and 3 different somatic patterns
      were seen: a- well preserved Sph reactivity around the soma and the proximal
      dendrites of histologically normal neurons; b- few chromatolytic neurons showing
      large numbers of dot-like presynaptic terminals around the cell body and in a
      "fused" pattern; c- intense, diffuse, and homogeneous reactivity of some neurons.
      Attenuation of Sph reactivity in the AH neuropil, to its complete loss, was
      observed in all ALS cases. In addition to patterns a-c, two additional
      microscopic findings were noted in ALS: d- chromatolytic neurons showing complete
      absence of Sph reactivity; e- absence of Sph reactivity around the soma and the
      proximal dendrites of histologically normal surviving neurons. Our findings
      demonstrate that there is a decrease in Sph immunostaining with aging, thus
      suggesting an alteration in dendritic networks of the AH with aging. Changes in
      the pattern of Sph immunoreactivity in cell bodies may represent synaptic
      plasticity and/or degeneration. Reinnervation may also be a possible mechanism as
      a response to neuronal loss in oldest control cases. Sph reactivity results may
      thus lend support to the presence of superimposed aging components in ALS cases
      which may give an insight into explaining the increasing severity of the disease
      which is encountered with advancing age.

PMID- 9013420
TI  - Lower 3H-paroxetine binding in cerebral cortex of suicide victims is partly due
      to fewer high affinity, non-transporter sites.
AB  - Suicide has been associated with decreased serotonin transmission. Measurement of
      concentrations of serotonin, its precursors tryptophan (TRY) and 5
      hydroxytryptophan (5-HTP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA),
      have been used as indices of serotonin activity, and with serotonin transporter
      binding, are indices of the integrity of serotonin nerve terminals. Most previous
      studies have not distinguished high affinity transporter binding from a very
      similar nontransporter binding site, where binding is not dependent on Na+ or Cl-
      and that does not have a known functional role. We therefore, assayed binding
      kinetics in prefrontal (PFC) and temporal cortex (TC) in matched pairs of suicide
      victims and controls using the selective ligand 3H-paroxetine, and employing 1
      microM sertraline to define specific binding to the transporter and 10 microM
      sertraline which also displaces binding to the high affinity, nontransporter
      site. In addition, we measured concentrations of TRY, 5-HTP, serotonin and 5-HIAA
      in the same brain areas. The total number of 3H-paroxetine transporter and
      nontransporter binding sites (Bmax), was lower in the suicide group compared to
      controls in both Brodmann area 9 (prefrontal cortex; p = 0.02) and in Brodmann
      area 38 (temporal cortex, p = 0.01). In contrast, no differences were found in
      the number of high affinity transporter binding sites and concentrations of
      serotonin, 5-HIAA, 5-HTP or TRY (p > 0.05). We conclude that the number of
      serotonin transporter sites is not altered in Brodmann area 9 in suicide, and
      that fewer 3H-paroxetine and 3H-imipramine binding sites found in this region of
      cerebral cortex of suicides may be explained by a reduction in the nontransporter
      binding sites.

PMID- 9013421
TI  - The predictive value of P300-amplitudes in the course of schizophrenic disorders.
AB  - Auditory P300-amplitudes have been found to be correlated with the social
      functioning and with the impairment in daily life by negative symptoms in cross
      sectional studies. In this prospective longitudinal study, the correlation of
      auditory P300-amplitudes registrated at the index examination was investigated
      with the clinical outcome after an average of 2.4 years. Based on previous
      studies, only schizophrenic patients who were in a stabilized residual state were
      included in the study. Reference-independent P300-parameters of the index
      examination were correlated with axis V of DSM-III-R (GAF), with the Brief
      Psychiatric Rating Scale (BPRS) and with the Scale for Assessment of Negative
      Symptoms (SANS) assessed at the follow-up examination. The correlation of index
      P300-amplitude with social functioning at follow-up was significant. No
      correlations of index P300 with the current symptomatology at follow-up, as
      expressed by BPRS and SANS was found, however. The results indicate a predictive
      value of the P300-amplitude on the clinical outcome in terms of social
      functioning of schizophrenic patients.

PMID- 9013422
TI  - Transcranial magnetic stimulation downregulates beta-adrenoreceptors in rat
      cortex.
AB  - Recently, a method for transcranial magnetic stimulation (TMS) of the brain has
      been developed. Thus, it is possible to explore neurochemical and behavioral
      effects of TMS in rats. Repeated TMS (9 days) reduced beta-adrenergic receptor
      binding in cortex, as does electroconvulsive shock (ECS) and other antidepressant
      treatments. Thus TMS appears to be a potential antidepressive treatment.

PMID- 9013423
TI  - Alpha N-catenin expression in the normal and regenerating chick sciatic nerve.
AB  - The Ca(2+)-dependent intercellular adhesion molecule cadherin is known to be
      linked to the cytoskeleton by the protein catenin, an association of which
      appears to be important for the cell-adhesion function of cadherin. Catenin
      consists of three subtypes-alpha, beta, and gamma. In our previous study, N
      cadherin was shown to be localized on the plasmalemma of normal and regenerating
      chick peripheral nerve. Thus, as alpha N-catenin is a subtype of alpha-catenin
      (which is specifically associated with N-cadherin), we investigated the
      immunolocalization of alpha N-catenin in normal and regenerating chick sciatic
      nerve. In normal nerve, unmyelinated axons exhibited either intense or weak alpha
      N-catenin immunoreactivity throughout the axoplasm, whereas myelinated axons were
      completely immunonegative. Regenerating axons, including those derived from
      parent myelinated axons, showed alpha N-catenin immunoreactivity of variable
      intensities in growth cones and axon shafts. Schwann cells were invariably devoid
      of immunoreactivity. Thus alpha N-catenin is not necessarily bound to the surface
      plasmalemma, but is distributed throughout the cytoplasm, suggesting that most
      alpha N-catenin molecules are dissociated from N-cadherin.

PMID- 9013424
TI  - Two classes of bipolar cell in the retina of the skate Raja erinacea.
AB  - We have used immunoreactions against serotonin and protein kinase C to visualize
      two distinct classes of bipolar cell in the all-rod retina of the skate, Raja
      erinacea. To enhance the immunoreaction in serotonin-accumulating bipolar cells,
      prior to fixation, some retinas were incubated in Ringer's solution containing
      serotonin and pargyline. We found the somata of serotonin-accumulating bipolar
      cells to be located slightly distal to the midline of the inner nuclear layer.
      With increasing eccentricity from the visual streak, the size of the perikarya
      increases, concomitant with a decline in density of their distribution. Dendrites
      emanate from stout primary stalks and branch out before reaching the outer
      plexiform layer. Axons are bistratified within the inner plexiform layer with
      ramifications at the border of strata 1 and 2 and in stratum 4. The overall
      morphology of serotonin-accumulating bipolar cells is similar to that of
      serotonin-accumulating OFF bipolar cells of other non-mammalian vertebrates.
      Protein kinase C immunoreactive cells display the typical appearance of rod
      bipolar cells. Somata of protein kinase C immunoreactive bipolar cells are
      spindle-shaped and located distal to the serotonin-accumulating bipolar cells.
      Dendrites of these bipolars do not ramify before reaching the outer plexiform
      layer. Thin axons of protein kinase C immunoreactive bipolar cells end in large,
      club-shaped terminals in stratum 5 of the inner plexiform layer, bearing a
      striking similarity to axon terminals of mammalian ON rod bipolar cells. Our
      findings suggest that the all-rod retina of the skate contains at least two
      distinct vertical pathways including an OFF bipolar cell pathway in addition to a
      classical rod ON bipolar pathway.

PMID- 9013425
TI  - An unbiased method for estimation of total epidermal nerve fibre length.
AB  - It is of interest to quantify accurately lineal biological features such as nerve
      fibres, capillaries, and tubules for studies of development and diseases such as
      sensory neuropathy, and for evaluation of therapeutic regimens in humans and
      animal models. An unbiased stereological method to sample and estimate total
      length of immunostained epidermal nerve fibres by using vertical sections of
      punch skin biopsies from two human volunteers is presented. The essential steps
      in the procedure are as follows: (1) serially section the skin punch in a random
      plane perpendicular to the cutaneous surface; (2) immunostain a known fraction of
      total sections with antibody specific for nerve fibres; (3) orient a test line
      grid over the epidermis; and (4) count intersections between test lines and
      immunostained epidermal nerve fibres. The optical fractionator method is employed
      to estimate total length of immunostained epidermal nerve fibres in the biopsy.
      By using these techniques the total length of nerve fibre in a defined region can
      be determined without methodological bias, assumptions or correction factors.

PMID- 9013426
TI  - Ultrastructural study on the interaction of native and cationized albumin-gold
      complexes with mouse brain microvascular endothelium.
AB  - The main objective of this ultrastructural study was to gain insights into the
      cellular mechanisms responsible for the enhanced brain uptake of blood-borne
      cationized albumin observed by several authors utilizing quantitative
      methodology. Mice were injected intravenously or into the common carotid artery
      (in vivo experiments) or perfused in situ with solutions of native or cationized
      bovine serum albumin complexed with colloidal gold (BSA-G or cBSA-G
      respectively). The results indicate that: (1) the main drawbacks of in vivo
      experiments are very intense phagocytosis of the tracer particles by Kupffer
      cells located in the liver sinusoids and also escape of the tracer through
      capillaries of skeletal and heart muscles. This results in a rapid decline of the
      concentration and disappearance of the circulating tracer particles; (2) BSA-G
      and cBSA-G both in vivo (up to 30 min circulation) or after perfusion in situ (up
      to 15 min) do not cross the wall of brain microvessels representing the blood
      brain barrier; (3) enhanced entrance of cationized albumin into the brain occurs
      through fenestrated endothelium of the capillaries located in the examined
      circumventricular organs (median eminence and neurohypophysis). Although BSA-G is
      also transported by these fenestrated capillaries, this process is evidently less
      intense than in the case of cBSA-G; (4) the enhanced passage of cBSA-G across
      fenestrated capillaries occurs mainly via vesicular transport (adsorptive
      transcytosis), through transendothelial channels and eventually through
      interendothelial junctional clefts; (5) the fenestrated capillaries of the
      choroid plexus appear to be less permeable for both tracers than those located in
      the other circumventricular organs.

PMID- 9013427
TI  - Intrinsic organization and monoaminergic innervation of the suprachiasmatic
      nucleus transplanted to adult rats. A light- and electron-microscopic study.
AB  - Light- and electron-microscopic immunocytochemistry was used to investigate
      grafts of foetal hypothalamic tissue implanted close to the site of the
      suprachiasmatic nucleus in adult rats with bilateral surgical ablation of this
      nucleus. The transplants contained vasoactive intestinal peptide and vasopressin
      cell clusters, which have previously been shown to characterize functional
      suprachiasmatic nucleus grafts. Vasoactive intestinal peptide and vasopressin
      neurons presented synaptic features that have not been described in the native
      suprachiasmatic nucleus. More specifically, their terminals within the graft were
      involved in 'double' synapses with separate unlabelled dendrites. Moreover, in
      dually stained sections, an unexpected synaptic investment of vasoactive
      intestinal peptide neurons by vasopressin endings was detected, which revealed
      reversed vasoactive intestinal peptide/vasopressin interactions compared to those
      described in the native nucleus. These observations could reflect some immature
      features of the grafted neurons. Ultrastructural relationships of monoaminergic
      fibres arising from host and/or intragraft neurons were also examined. Within the
      engrafted suprachiasmatic nucleus, tyrosine hydroxylase-labelled fibres, which
      probably belonged to cografted dopaminergic neurons, showed normal patterns of
      distribution and synaptic connections, with no preferential relationships with
      vasoactive intestinal peptide or vasopressin neurons. Serotoninergic axons
      arborized within transplants but, in agreement with previous data showing an
      inhibitory influence of the suprachiasmatic nucleus on ingrowing serotoninergic
      fibres, they had no predilection for the area corresponding to that nucleus. In
      spite of their relative scarcity, serotoninergic fibres within the engrafted
      suprachiasmatic nucleus showed an almost normal synaptic incidence, but synapses
      were not predominantly shared with the vasoactive intestinal peptide neurons,
      known to be their major targets in the native nucleus. This may contribute not
      only to the failure of functional grafts to synchronize with environmental
      conditions, but also to the inability of transplants to restore hormonal rhythms
      such as estrous cyclicity.

PMID- 9013428
TI  - How best to determine magnesium requirement: need to consider cardiotherapeutic
      drugs that affect its retention.

PMID- 9013429
TI  - The metabolic roles, pharmacology, and toxicology of lysine.
AB  - L-lysine monohydrochloride (LMH) is widely available to the public as a
      nonprescription oral supplement. Most of the pharmaceutical-grade product is used
      as a suppressant of recurrent herpes simplex infections. Recent publications
      indicate the possibility of other therapeutic uses, e.g., in cardiovascular
      disease and osteoporosis. These and other potential applications are surveyed and
      evaluated in this review with suggestions for further study. Data on toxicity are
      reviewed and recommendations made regarding safety of chronic dosage levels.

PMID- 9013430
TI  - Magnesium supplementation in patients with congestive heart failure.
AB  - OBJECTIVE: To evaluate several potential clinical indicators of magnesium status
      (diet, blood, urine, 24-hour load retention) in patients with congestive heart
      failure before, during, and after oral magnesium supplementation. METHODS: Twelve
      patients with New York Heart Association class II-III heart failure and 12 age
      and sex matched healthy control subjects were supplemented with 10.4 mmol oral
      magnesium lactate for 3 months. For the determination of magnesium status,
      samples of whole blood, serum, plasma, red blood cells, and urine (24-hour) were
      collected. Four-day dietary intake records were reviewed. A 4-hour IV magnesium
      load retention study was performed before and 3 months after magnesium
      supplementation. A non-supplemented control group was similarly studied. RESULTS:
      At baseline, magnesium intakes for all groups were below the RDA. No significant
      differences were seen in serum, plasma, ultrafiltrates of serum or plasma or red
      cell magnesium concentrations among groups over time. At baseline 5/27 subjects
      (19%) compared to 11/27 subjects (41%) after supplementation demonstrated normal
      magnesium retentions (< 25%). Magnesium excretions among groups were
      significantly different during supplementation. Percent magnesium retentions
      among groups were not different. CONCLUSIONS: Supplementation with 10.4 mmol oral
      magnesium daily for 3 months did not significantly alter blood levels or
      magnesium retention; however, patients demonstrated lower retention of magnesium
      after supplementation. Differences in magnesium retention was not related to
      basal magnesium intake, blood levels or excretion. Unfortunately, even an
      intensive effort at characterizing magnesium status did not identify a clinical
      indicator of utility for differentiating patients with congestive heart failure
      before, during, and after 3 months of magnesium supplementation.

PMID- 9013431
TI  - Aortic antioxidant defense and lipid peroxidation in rabbits fed diets
      supplemented with different animal and plant fats.
AB  - OBJECTIVE: To test the hypothesis that dietary fats, depending on the fat source,
      may modulate aortic lipid peroxidation and antioxidant protection. METHODS:
      Rabbits were fed a low fat (LF, 2 g/100 g corn oil) diet or LF enriched with 16
      g/100 g (w/w) of corn oil (CO), corn oil plus cholesterol (23.5 mg/100 g diet, CO
      + C), bovine milk fat (MF), chicken fat (CF), beef tallow (BT) or lard (L). After
      a 30-day feeding period, aortic lipid peroxidation, as well as antioxidant
      enzymes and vitamin E were measured. RESULTS: In rabbits fed CO or L, aortic
      TBARS (a marker of lipid peroxidation) and total glutathione concentrations were
      greater but vitamin E levels were lower compared with the LF treatment. Moreover,
      in rabbits fed CO, elevated activities of glutathione peroxidase and glutathione
      reductase but lowered activity of superoxide dismutase were observed. In rabbits
      fed the remaining high fat diets, including the CO + C diet, aortic lipid
      peroxidation and antioxidant activities/levels did not differ from those fed LF.
      Feeding rabbits high-fat diets for 30 days did not induce aortic lipid
      deposition. CONCLUSIONS: The present results indicate CO, and possibly L, as the
      fat sources which significantly increase aortic oxidative stress. Because long
      term disturbances in redox status may be implicated in atherogenesis, excessive
      dietary intake of CO or L may significantly contribute to the injury of the
      vessel wall.

PMID- 9013432
TI  - Vitamin A (retinol) status of first nation adults with non-insulin-dependent
      diabetes mellitus.
AB  - OBJECTIVE: Poorly controlled insulin-dependent diabetes mellitus (IDDM) has been
      reported to be associated with an impaired metabolic availability of vitamin A.
      The purpose of this study was to examine vitamin A status in a select group with
      non-insulin dependent diabetes mellitus (NIDDM). METHODS: Participants included
      106 (male, female, > 40 years) Plains Cree adults residing in central Alberta,
      with NIDDM (n = 59) and non-diabetic controls (n = 47). Non-fasting plasma
      samples were collected and concentrations of retinol, zinc, alpha-tocopherol,
      total protein, albumin, retinol binding protein (RBP), transthyretin (TTR),
      cholesterol, triglycerides, glucose, insulin, and fructosamine were determined.
      Multiple linear regression was used to identify predictors of plasma RBP
      concentration. Three repeated 24-hour recalls and a food frequency questionnaire
      were used to determine vitamin A intakes. RESULTS: Diabetic subjects had similar
      intake and plasma concentration of vitamin A compared to controls. Factors such
      as alpha-tocopherol, zinc, total protein, albumin, and TTR, which are known to
      influence vitamin A metabolism, also remained unaffected in subjects with
      diabetes. Plasma levels of vitamin A carrier protein (RBP), however, were
      elevated in diabetic subjects, possibly as a result of hyperinsulinemia. The
      subjects with diabetes had many characteristics of the insulin resistant
      syndrome, including central obesity, hypertension, and hypertriglyceridemia. Poor
      metabolic control, based on plasma glucose, was a significant predictor of RBP
      concentration in diabetic subjects. CONCLUSIONS: The plasma concentration of RBP
      was elevated in diabetic subjects and was associated with normal circulatory
      availability of retinol. The subjects with NIDDM, characterized by insulin
      resistance without insulin deficiency, thus, appear to be associated with normal
      vitamin A status.

PMID- 9013434
TI  - Nutritional intake of women and men on the NCEP Step I and Step II diets.
AB  - OBJECTIVE: Restriction of dietary fat and cholesterol are recommended for
      treating hyperlipidemia, but may alter vitamin or mineral intakes. We evaluated
      changes in nutrients of individuals taught the National Cholesterol Education
      Program (NCEP) Step II diet. METHODS: Subjects participated in a randomized
      controlled trial of the cholesterol-lowering effect of the NCEP Step II diet.
      Eligibility criteria included elevated fasting plasma LDL-cholesterol, no lipid
      altering medications, and diet not already fat-modified. Subjects attended eight
      weekly dietitian-led classes. Four-day food records collected 6 months post
      intervention were compared to baseline records. RESULTS: Of 409 subjects with
      complete data, 123 met Step I and 166 met Step II diet criteria. Intakes of
      micronutrients associated with fruits and vegetables (beta-carotene and vitamin
      A, vitamin C, folic acid, magnesium, and potassium) increased on both diets.
      Patterns of decreased mean intake and/or fewer subjects consuming 2/3 Recommended
      Dietary Allowance were seen for calcium, vitamin E, and zinc. CONCLUSIONS: NCEP
      Step I and II diets generally match or exceed unmodified diet for vitamin and
      mineral content. Premenopausal women do not appear to be at increased risk of low
      iron intake. Vitamin E intake decreases, although the significance is unknown in
      the context of lower fat intake and increased intake of other antioxidants. Diet
      counseling and materials should encourage sources of calcium for women, and zinc
      for both women and men.

PMID- 9013433
TI  - Effect of beta-glucan level in oat fiber extracts on blood lipids in men and
      women.
AB  - OBJECTIVE: An active hypolipidemic component in oats, the soluble fiber beta
      glucan, has been concentrated in an oat fiber extract. The oat fiber extract has
      been used to replace fat in food products. This study was designed to determine
      if moderate levels of oat fiber extract could be incorporated into a typical diet
      and whether plasma lipids could be reduced by the amount of beta-glucan added to
      the diet. METHODS: Oat fiber extracts containing low (1% by weight) or high (10%
      by weight) beta-glucan were fed to 23 mildly hypercholesterolemic subjects (seven
      men and 16 women). A maintenance diet was fed for 1 week followed by diet
      containing an oat extract for 5 weeks each in a crossover pattern. Five percent
      of the energy from fat in the maintenance diet was replaced with the oat extract
      in the experimental diets. Caloric intake was adjusted to try to maintain each
      subject's initial weight. Fasting blood was collected several days apart after
      separate 12 hour fasts the end of each period. Plasma was analyzed for
      triglycerides, total cholesterol, and lipoprotein cholesterol fractions. RESULTS:
      HDL, HDL2, and VLDL cholesterol, and triglyceride levels after the oat extract
      diets were not significantly different from those after the maintenance diet.
      Total and LDL cholesterol levels decreased significantly (p < 0.001) from
      maintenance levels after both diets containing the oat extracts. Total
      cholesterol levels after the higher beta-glucan extract diet were significantly
      lower than those after the low beta-glucan diet. CONCLUSIONS: Beneficial
      reduction of cholesterol was obtained with modest amounts of oat extract
      incorporated into the diet. A significant dose response due to beta-glucan
      concentration in the oat extract was observed in total cholesterol levels.

PMID- 9013435
TI  - Epidemiologic study of trace elements and magnesium on risk of coronary artery
      disease in rural and urban Indian populations.
AB  - OBJECTIVE: To determine the association of trace elements and magnesium with risk
      of coronary artery disease (CAD) in rural and urban populations of India. DESIGN
      AND SETTING: Cross-sectional surveys on the randomly selected municipal streets
      in Moradabad city and one village in Moradabad tahsil in North India. SUBJECTS
      AND METHODS: There were 162 rural (86 men and 96 women) and 152 urban (80 men and
      72 women) subjects between 26 to 65 years of age. Evaluations were obtained by
      physician- and dietitian-administered, validated questionnaires, physical
      examination, electrocardiogram and blood examination. RESULTS: The prevalence of
      CAD and coronary risk factors was 2.5 times higher in the urban population
      compared to rural subjects (8.6 vs. 3.0%). In rural subjects, dietary intakes and
      plasma levels of vitamins and minerals were comparable with those of urban
      subjects except for higher dietary intake of magnesium in rural subjects and
      higher plasma vitamin A level in urban subjects. In both rural and urban
      subjects, low serum zinc (80 +/- 82 vs. 110 +/- 11.0 micrograms/dl, p < 0.05) and
      magnesium levels (1.60 +/- 0.36 vs. 1.71 +/- 0.41 mEQ/L, p < 0.05) and lower
      zinc/copper ratio (0.58 +/- 0.08 vs. 1.11 +/- 0.25 p < 0.50) were inversely
      associated with CAD. Serum levels of copper and iron were significantly higher
      and plasma levels of antioxidant vitamins A, E and C and beta-carotene were
      significantly lower in patients with CAD compared to the rest of the subjects. In
      both rural (7.1 +/- 1.2 mg/day) and urban subjects (8.6 +/- 1.6 mg/day), zinc
      consumption was half of the recommended dietary allowances. Higher prevalence of
      CAD in urban compared to rural subjects was attributed to higher dietary fat
      intake and higher prevalence of risk factors in urban subjects. CONCLUSIONS: The
      findings suggest that lower serum levels of zinc and magnesium and lower zinc
      copper ratio were inversely associated with CAD. It is possible that urban
      populations with higher risk of CAD may benefit by decreasing dietary fat intake
      and by increasing their intake of foods rich in zinc and magnesium.

PMID- 9013436
TI  - The effects of exercise intensity on body composition, weight loss, and dietary
      composition in women.
AB  - OBJECTIVE: There is controversy over whether exercise and/or exercise intensity
      has an effect on total caloric intake or diet composition. The purpose of this
      study was to test the effect of exercise intensity without dietary manipulation
      on body composition and/or weight loss and to determine whether exercise
      intensity affected total caloric intake or diet composition in normal weight
      young women. METHODS: Fifteen women aged 18 to 34 years with a maximal oxygen
      consumption average or below on the Palo Alto norms served as subjects. Subjects
      were randomly assigned to: 1) low heart rate intensity exercise group (LI, N = 7)
      which exercised 40 to 45 minutes approximately four times weekly at a mean heart
      rate of 132 beats per minute (bpm); 2) high heart rate intensity group (HI, N =
      8) which exercised 40 to 45 minutes approximately four times weekly at a mean HR
      of 163 bpm. All subjects were given a maximal exercise test prior to and during
      weeks eight, 12 and 16. The first 4 weeks served as a control period, followed by
      approximately 11 weeks of exercise. Each subject recorded her dietary intake for
      1 complete week, including a weekend, during weeks 2, 6, 10 and 14 of the study.
      RESULTS: VO2 max increased (p < .05) in HI (29 +/- 6 ml/kg/minute to 38 +/- 7)
      but did not change in LI (36 +/- 5 to 38 +/- 7). Percent fat decreased in HI (p <
      .05) (27 +/- 7 to 22 +/- 4) but was unchanged in LI (22 +/- 6 to 21 +/- 6). The
      weekly intake of total kcal, carbohydrate, protein and fat did change
      significantly for either group. The weekly intake of saturated fat declined
      significantly (p < .05) in HI (21.2 +/- 5.8 g to 14.9 +/- 5.5 g); their weekly
      intake of cholesterol also decreased (p < .05) between months 2 to 3 (249 +/- 109
      mg to 159 +/- 58 mg). No other differences in dietary intake between groups were
      found. CONCLUSION: High heart rate intensity exercise training without dietary
      manipulation resulted in a decrease in body fat, but not weight change, as well
      as a decrease in the intake of saturated fat and cholesterol in normal weight
      young women. These changes were not observed after low heart rate intensity
      training.

PMID- 9013437
TI  - Dose-dependent effect of octreotide on nitrogen retention and glucose homeostasis
      in response to endotoxemia in parenterally fed rats.
AB  - OBJECTIVE: This study compared the effect of different doses of octreotide on
      glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide
      and parenteral nutrition infusions. METHODS: Sixty-six male Sprague Dawley rats
      (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus
      continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day
      (LPS), PN plus LPS plus octreotide at 10 micrograms/kg/day (LPS + Oct 10), 100
      micrograms/kg/day (LPS + Oct 100), or 1000 micrograms/kg/day (LPS + Oct 1000) for
      48 hours. Prior to randomization all animals received isocaloric and
      isonitrogenous PN (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept
      nil per os except for water ad libitum. Nitrogen balance, urinary 3
      methylhistidine/creatinine ratio, serum glucose concentration, and incidence of
      glycosuria were compared between groups. Serum urea nitrogen (SUN) changes were
      incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncan's
      multiple range test, and Fisher's Exact Test were used for statistical analysis.
      RESULTS: Nitrogen balance (mg/48 hours) was significantly lower in all four
      groups receiving LPS +/- Oct when compared to the control group receiving PN
      alone. SUN (mg/dL) was significantly higher in all four groups receiving LPS +/-
      Oct when compared to control. There were no statistically significant differences
      in nitrogen balance or SUN among the four groups receiving LPS +/- Oct. The ratio
      of urinary 3-methylhistidine/ creatinine was significantly higher in the LPS +
      Oct 1000 group compared to the PN group (0.77 +/- 0.37 vs. 0.42 +/- 0.24, p <
      0.05). Serum glucose concentrations and incidence of glycosuria among the five
      groups were not significantly different. CONCLUSIONS: Endotoxin significantly
      reduces nitrogen balance compared to controls fed PN. Octreotide does not
      significantly improve nitrogen retention or glucose homeostasis in endotoxemic
      parenterally fed rats.

PMID- 9013438
TI  - Serum levels of unbound free fatty acids. I: Normative data in term newborn
      infants.
AB  - BACKGROUND: Free fatty acids (FFA) play essential roles in maintaining
      physiologic homeostasis in the newborn infant. Most of the FFA in serum is
      carried in complex with albumin, but a small fraction remains unbound in the
      aqueous phase. OBJECTIVE: This study's goal is to report the values of serum
      levels of unbound free fatty acids (FFAu) in pregnant women and their newborn
      infants at term gestation. METHODS: The measurements were made possible by the
      availability of the fluorescent probe for unbound FFA, acrylodated intestinal
      fatty acid binding protein (ADIFAB). Twenty-two mother-infant pairs were enrolled
      in the study. Maternal levels were obtained immediately before delivery, cord
      levels at the time of delivery, and infant levels after 24 hours of age. RESULTS:
      The level of FFAu measured in maternal samples was 11.8 +/- 4 nM, in cord samples
      9.2 +/- 4 nM, and in infants 13.9 +/- 3 nM. These population averages are
      considerably greater than those observed in healthy adults (7.5 +/- 2.5 nM). No
      correlation was found between cord levels and birthweight, gestational age, labor
      duration, mode of deliver, and infant or maternal temperature. CONCLUSIONS: This
      investigation is the first to measure FFAu in a group of mothers and their
      infants and provides the technique for future investigations of the biologic
      activity of free fatty acids.

PMID- 9013439
TI  - Serum levels of unbound free fatty acids. II: The effect of intralipid
      administration in premature infants.
AB  - BACKGROUND: Fatty acids (FFA) are key nutrients in maintaining physiologic
      homeostasis and in the form of Intralipid administration, they are important
      sources of nutrition in the premature newborn infant. Complexed with albumin,
      fatty acids have a small but important fraction that remains unbound in the
      aqueous phase. OBJECTIVE: The goal of this study was to examine the levels of
      serum levels of unbound free fatty acids (FFAu) in premature newborns following
      Intralipid administration. METHOD: A fluorescent probe acrylodated intestinal
      fatty acid binding protein (ADIFAB) was used to measure (FFAu) before Intralipid
      and during increasing rates of infusion. RESULTS: There were significant
      differences between (FFAu) values obtained before Intralipid and levels after the
      infusion of 1.0, 2.0, and 3.0 g/kg/day (p < 0.05). Regression analysis of
      Intralipid dose and FFAu yielded an r = 0.438 and the following relationship:
      [FFAu] = 26.39 + 3.60 * IL (g/kg/day). CONCLUSIONS: Intralipid administration
      results in significant elevation of FFAu in the very low birth weight infant.

PMID- 9013440
TI  - Differences in diet and food habits between patients with gallstones and
      controls.
AB  - OBJECTIVE: To compare the food, energy, macronutrient and micronutrient intake of
      patients with gallstones to those of a control group of similar demographic
      characteristics. DESIGN: Patient-control study. SUBJECTS: 54 gallstone patients
      and 46 control subjects. METHODS: Two 24-hour dietary recalls and a "food
      frequency intake" questionnaire were obtained from patients and controls. In both
      groups, the presence/absence of gallstones was confirmed by ultrasonography.
      Participants answered a questionnaire on their physical activity patterns.
      RESULTS: Gallstone patients consumed less food per day (g/day) and less fish and
      fruits than did control subjects. They also showed greater intakes of cereals,
      oils, sugars and meats than did control subjects and ate fewer meals per day,
      tending to omit evening snacks and more substantial evening meals. Further,
      patients spent less time walking and slept more than did control subjects. They
      also experienced fluctuations in body weight with greater frequency. Patients
      consumed more total calories (energy) and fats (especially monounsaturated fatty
      acids and saturated fatty acids), and less fiber, folate and magnesium than did
      control subjects. Women with gallstones were shown to have significantly higher
      intakes of total fats, monounsaturated fatty acids, saturated fatty acids and
      cholesterol, and significantly lower intakes of fiber, folate, magnesium, calcium
      and vitamin C than control women. For all vitamins and minerals studied, patients
      showed a greater percentage of intakes below those recommended. CONCLUSIONS:
      Dietary intervention might provide a method of avoiding the recurrence of
      gallstones as well as a method of prevention control subjects.

PMID- 9013441
TI  - Thiamin and cognitive impairment.

PMID- 9013442
TI  - Labeling of trans fatty acids.

PMID- 9013443
TI  - Aquaporin-1 water channel expression in human kidney.
AB  - The pattern of aquaporin-1 water channel protein (AQP1) expression in the human
      kidney was analyzed by immunocytochemistry using semi-thin and optimized high
      resolution immunoelectron microscopy based on freeze-substituted and Lowicryl
      HM20 embedded tissue. In addition, in situ hybridization was used to determine
      AQP1 mRNA distribution. Immunoblots revealed a 28-kd band and a 35- to 45-kd band
      corresponding to unglycosylated and glycosylated AQP1. Glomerular capillary
      endothelium exhibited extensive AQP1 labeling, whereas glomerular podocytes and
      Bowman's capsule epithelium were unlabeled. AQP1 was localized in the proximal
      tubule, including the neck region directly connected to the glomerulus. However,
      there was a marked difference in the level of expression between cross-sections
      of the convoluted part and the proximal straight tubules, the latter displaying
      the most intense labeling. AQP1 labeling continued uninterrupted from the
      proximal straight tubule into descending thin limbs in outer medulla. Abrupt
      transitions from heavily labeled to unlabeled segments of thin limbs were
      observed, primarily in the inner medulla. This may represent the transition from
      the water-permeable thin descending limb to the water-impermeable thin ascending
      limb. In addition, heavy labeling of fenestrated endothelium was also observed in
      peritubular capillaries in cortex, outer medulla, and inner medulla.
      Immunolabeling controls were negative. In situ hybridization documented a marked
      difference in AQP1 mRNA levels within the proximal tubule, with the greatest AQP1
      mRNA expression in straight proximal tubules. Glomeruli also showed marked
      signals, and descending thin limbs exhibited extensive expression in exact
      concordance with the immunocytochemical results. It was concluded that: (1) AQP1
      is present in all proximal tubule segments, including segment 1 and the neck
      region, but there is a pronounced difference in expression levels with respect to
      both protein and mRNA levels; (2) AQP1 labeling is observed in the endothelium of
      fenestrated peritubular capillaries, as well as fenestrated glomerular
      capillaries; (3) AQP1 labeling continues directly from proximal tubules to
      descending thin limbs; and (4) abrupt transitions from labeled to unlabeled thin
      limb epithelium are noted.

PMID- 9013444
TI  - Reduced renal medullary water channel expression in puromycin aminonucleoside-
      induced nephrotic syndrome.
AB  - The aquaporins are molecular water channels that mediate transcellular water
      transport across water-permeable epithelia. To investigate the cause of the
      concentrating defect in the nephrotic syndrome, immunoblotting using membrane
      fractions from inner medulla was utilized to assess the level of expression of
      four aquaporin water channels in vehicle-treated versus puromycin aminonucleoside
      (PAN)-treated rats. Scanning electron microscopy demonstrating loss of glomerular
      foot processes and measurements of urinary protein excretion confirmed the
      efficacy of the PAN treatment. In rats receiving PAN, there was an increase in
      plasma vasopressin, without a change in plasma sodium concentration. Inner
      medullary tissue hypertonicity was sustained in PAN-treated rats while the
      urinary osmolality was low, pointing to defective osmotic equilibration across
      the collecting ducts in PAN-nephrosis. Among collecting duct aquaporins, there
      was an 87% decrease in aquaporin-2 expression and a 70% decrease in aquaporin-3
      expression in the inner medulla, whereas aquaporin-4 expression was unaltered.
      Transmission electron microscopy of the inner medullary collecting ducts of PAN
      treated rats showed normal-appearing cells. Thus, PAN-nephrosis is associated
      with an extensive downregulation of collecting duct water channel expression
      despite increased circulating vasopressin, providing an explanation for the
      concentrating defect associated with the nephrotic syndrome.

PMID- 9013445
TI  - Direct evidence that thromboxane mimetic U44069 preferentially constricts the
      afferent arteriole.
AB  - The thromboxane A2 (TXA2) mimetic U44069 has been demonstrated to reduce the GFR
      and filtration fraction of the normal isolated perfused rat kidney markedly,
      suggesting a predominant constriction of preglomerular vessels. To assess this
      possibility directly, effects of U44069 on the renal microvessels of the isolated
      perfused hydronephrotic kidney were examined. At 10(-6) mol/L, U44069 elicited a
      27 +/- 2% decrease in afferent arteriolar (AA) diameter (from 18.8 +/- 0.3 to
      13.7 +/- 0.3 micron, P < 0.001). In contrast, efferent arteriolar (EA) diameter
      decreased by only 9 +/- 1% (from 16.4 +/- 0.5 to 15.0 +/- 0.5 micron, P < 0.001).
      These effects on both AA and EA were completely reversed by the TXA2 receptor
      antagonist SQ29548. The calcium antagonist diltiazem reversed U44069-induced AA
      constriction by 83 +/- 5%. The U44069-induced EA constriction was insensitive to
      the vasodilator action of diltiazem at concentrations from 10(-8) to 10(-6)
      mol/L, but at 10(-5) mol/L, diltiazem increased the EA diameter significantly,
      albeit modestly. Nifedipine also reversed the U44069-induced AA constriction (81
      +/- 7%), but failed to inhibit the EA constriction at concentrations from 10(-9)
      to 10(-6) mol/L. These findings constitute the first direct evidence that a TXA2
      agonist preferentially constricts the afferent arteriole. Furthermore, the
      ability of both the calcium antagonist and SQ29548 to reverse the renal
      microvascular actions of TXA2 agonists suggests a potential utility of these
      agents in ameliorating TXA2-induced renal hemodynamic abnormalities.

PMID- 9013446
TI  - Role of endothelin receptor subtypes in the systemic and renal responses to
      endothelin-1 in humans.
AB  - The authors recently reported that infusion of endothelin-1 in humans to obtain
      pathophysiological plasma levels causes profound renal vasoconstriction and
      sodium retention. The relative roles of the ETA- and ETB-receptor subtypes in
      these effects in humans is unknown. Such information is essential in view of the
      recent introduction of endothelin-receptor blockers in clinical medicine. The
      study presented here was designed to define the role of the ETA- and ETB-receptor
      subtypes in the renal actions of endothelin-1 in humans. Systemic infusion of
      endothelin-1, a nonselective receptor agonist, was compared with infusion of
      equimolar dosages of the ETB-selective agonist endothelin-3 in healthy
      volunteers. Endothelin-1 infusion was associated with an approximate 2.5-fold
      increase in plasma levels of endothelin-1. This was accompanied by an increase in
      blood pressure by approximately 6 mm Hg (P < 0.05). During endothelin-1 infusion,
      RPF decreased from 642 +/- 42 to 480 +/- 36 mL/min (P < 0.05) and GFR from 121 +/
      4 to 109 +/- 7 mL/min (P < 0.05). Sodium excretion rate decreased during
      endothelin-1 infusion, from a baseline value of 182 +/- 33 to 84 +/- 28 mumol/min
      at the end of the endothelin-1 infusion. Endothelin-3 infusion also resulted in a
      approximate 2.5-fold increase of plasma levels of endothelin-3. However, in
      contrast to the endothelin-1 infusion, endothelin-3 had no effect on blood
      pressure, renal hemodynamics, and electrolyte excretion. These results suggest
      that the systemic and renal vasoconstrictor effects of endothelin-1 in humans are
      predominantly mediated by the ETA receptors.

PMID- 9013447
TI  - Differential regulation of the dual-specificity protein-tyrosine phosphatases
      CL100, B23, and PAC1 in mesangial cells.
AB  - The extracellular-signal-regulated kinase (ERK), the best described MAP kinase
      cascade, is a major signaling system by which cells transduce extracellular cues
      into intracellular responses. ERK is activated by phosphorylation both on
      tyrosine and threonine residues. Therefore, a new clas of protein-tyrosine
      phosphatases (PTPases) that exhibit dual catalytic activity toward both
      regulatory sites on ERK is of special interest in the control of intracellular
      signaling. This study examined the expression and regulation of the dual
      specificity PTPases CL100, B23, and PAC1. Findings included differential
      expression of these phosphatases in diverse cell lines and an expression of all
      three dual-specificity PTPases in human mesangial cells (HMC), thereby allowing
      investigation of their regulation in a single cell line. The MEK antagonist PD
      098059 and selective extracellular agonists of ERK were used to demonstrate the
      induction of CL100, PAC1, and B23 in response to activation of the ERK cascade.
      In contrast, anisomycin, an agonist of the recently described MAP kinases stress
      activated protein kinase (SAPK) and p38 MAP kinase, stimulated CL100 gene
      expression but had little effect on PAC1 and B23. This effect of anisomycin was
      partly inhibited in the presence of the p38 MAP kinase antagonist SB 203580. This
      study suggests a potential mechanism to regulate ERK activity through feedback
      inhibition by demonstrating the ERK cascade's induction of the dual-specificity
      PTPases CL100, PAC1, and B23. Moreover, this study suggests an ERK-independent
      induction of CL100 following stimulation of SAPK and p38 MAP kinase. This mode of
      induction of a phosphatase capable of inactivating ERK may play an important role
      in the cellular stress response.

PMID- 9013449
TI  - The effect of transfection of antisense cDNA for procollagen alpha 1 (IV) on
      stimulated proliferation in rat glomerular endothelial cells.
AB  - Glomerular endothelial cells were stably transfected with a pMAMneo-Blue vector
      recombinant for procollagen alpha 1 (IV) cDNA in the sense (S) or antisense (AS)
      orientation utilizing a calcium phosphate precipitation technique. Cellular
      clones resistant to G418 antibiotic were selected and expanded for further
      analysis. Immunofluorescence microscopy demonstrated less Type IV collagen in the
      AS clones (1.0 +/- 0.3) than in control parent (P) and S clones (2.0 +/- 0.4) (P
      < 0.05). Western analysis showed that the AS clones synthesized 20 +/- 10% of the
      205-kd alpha 1 (IV) chain of Type IV collagen compared with P cells (P < 0.05).
      As transfected clones demonstrated similar basal proliferation rates as control
      cells when cultured in 0.5% fetal calf serum (FCS), but failed to undergo fetal
      calf serum (FCS)-stimulated hyperplasia when grown on standard fibronectin-coated
      surfaces in 40% FCS (P < 0.05, compared with P- and S-transfected control cells).
      There were significant linear relationships between the presence of Type IV
      collagen as detected by either immunofluorescence microscopy or alpha 1 (IV)
      peptide chain quantitation by Western analysis and the ability of cells to
      undergo FCS-stimulated hyperplasia when grown on fibronectin (P < 0.05). Growth
      on a surface comprised of fibronectin plus Type IV collagen restored the capacity
      of AS transfected cells to respond to FCS stimulation (P < 0.001), but had no
      significant effect on the proliferative behavior of P or S cells. Measurements of
      AS RNA levels in these cells suggest that the inhibition of stimulated
      proliferation is determined by the presence of a threshold quantity of cellular
      AS RNA. These data demonstrate that Type IV collagen plays a critical role in
      conditioning glomerular endothelial cells to respond to proliferative stimuli.

PMID- 9013448
TI  - Overexpression of cell cycle inhibitors (p16INK4 and p21Cip1) and cyclin D1 using
      adenovirus vectors regulates proliferation of rat mesangial cells.
AB  - To elucidate the mechanisms of the cell cycle of mesangial cells, adenovirus
      vectors containing coding sequences of cyclin D1 (AxCAD1), p16INK4 (AxCAp16) and
      p21Cip1 (AxCAp21) were produced and investigated to determine whether transfer of
      these genes changes serum- and PDGF-induced proliferation of rat mesangial cells.
      Efficiency of the transfer of the genes was examined by Northern and Western blot
      analyses. The cell cycle of mesangial cells was evaluated by measurement of [3H]
      thymidine incorporation, flow cytometry, and cyclin-dependent kinase 4 kinase
      assay. Expression of cyclin D1, p16INK4 and p21Cip1 was observed from 24 h after
      the infection, and the expression increased up to 48 h. AxCAp16 and AxCAp21
      caused a significant inhibition in the [3H]-thymidine incorporation to 47% and
      76%, respectively. AxCAp16 and AxCAp21 also inhibited the mitogen-induced
      increase in cyclin-dependent kinase 4 kinase activity and reduced the percentage
      of cells in S phase. Coinfection of AxCAp16 with AxCAp21 showed no additive
      inhibition. Overexpression of cyclin D1 reduced cell size and increased the
      percentage of the cells in S and G2 phase. These findings suggest that p16INK4
      and p21Cip1 function as inhibitors of the proliferation of mesangial cells
      induced by growth-promoting factors and that deregulated expression of cyclin D1
      causes cell cycle disturbances. Adenovirus-mediated gene transfer of p16INK4 and
      p21Cip1 serves as a potential therapeutic approach to mesangial proliferative
      diseases.

PMID- 9013450
TI  - A reevaluation of routine electron microscopy in the examination of native renal
      biopsies.
AB  - Electron microscopy is routinely utilized in most centers in the evaluation of
      native renal biopsies. Several studies, primarily from the 1960s and early 1970s,
      provide justification for its use. Conducted by Siegel et al. (1), the largest
      study evaluated 213 consecutive renal biopsies and found that electron microscopy
      was needed for a correct diagnosis in 11%, as well as for confirmation or
      additional information in another 36%. However, nearly all of these studies were
      conducted before the use of immunofluorescence in renal biopsy diagnosis became
      widespread and before several new glomerular diseases and variants were
      described. In light of this situation and the expense of the procedure, the
      routine use of electron microscopy in native renal biopsies also examined by
      immunofluorescence and routine light microscopy was reevaluated. From January
      1996 to June 1996, 288 native renal biopsies were received, and all were
      evaluated by the same pathologist. Of those, 233 met criteria for inclusion in
      this study, which were > or = 5 glomeruli for light microscopy, > or = 2 for
      immunofluorescence, and > or = 1 for electron microscopy, not including globally
      scarred glomeruli. Light microscopy (hematoxylin and eosin, periodic acid-Schiff
      stains) and immunofluorescence--for immunoglobulin (Ig) G, IgA, IgM, C3, C1q,
      fibrinogen; kappa/lambda when needed--were evaluated on each biopsy within 48 h
      of receipt, and a preliminary diagnosis was recorded if possible. Electron
      microscopy was then performed, and a final diagnosis was made. In 50 cases (21%),
      electron microscopy was needed to make the final diagnosis; in two of these
      cases, the preliminary diagnosis was incorrect, and in 48, a firm preliminary
      diagnosis could not be made. In the other cases, the preliminary diagnosis was
      correct, but in 48 (21%), ultrastructural study was felt to provide important
      confirmatory data, and in eight cases (3%), an additional, unrelated diagnosis
      was supported by the ultrastructural findings. Diagnoses most frequently
      requiring electron microscopy included minimal change nephropathy, early diabetic
      nephropathy, membranous lupus nephritis, membranoproliferative
      glomerulonephritis, postinfectious glomerulonephritis, thin basement membrane
      nephropathy (or exclusion of this in cases of otherwise unexplained hematuria),
      and human immunodeficiency virus-associated nephropathy (or exclusion of it in
      cases of collapsing glomerulopathy). Common diagnoses usually not requiring
      electron microscopy included IgA nephropathy, diffuse proliferative lupus
      nephritis, focal segmental glomerulosclerosis (not collapsing glomerulopathy
      variant), pauci-immune crescentic glomerulonephritis, acute interstitial
      nephritis, and amyloid nephropathy. This study confirms that, as was the case 20
      to 30 yr ago, electron microscopy provides useful diagnostic information in
      nearly half of native renal biopsies. If electron microscopy cannot be performed
      routinely on all such biopsies, it is recommended that tissue for ultrastructural
      studies be set aside in each case.

PMID- 9013451
TI  - Dominantly transmitted glomerulocystic kidney disease: a distinct genetic entity.
AB  - Glomerulocystic kidney disease (GCKD) is a relatively rare condition with both a
      sporadic and familial occurrence. Pathologically, GCKD is characterized by cystic
      dilatation of Bowman's space and the initial proximal convoluted tubule. As a
      heritable disorder, GCKD has primarily been recognized in infants with a family
      history of classic, autosomal dominant polycystic kidney disease (ADPKD).
      Dominantly transmitted GCKD associated with either hypoplastic or normal-sized
      kidneys has also been reported in older children and adults. A large, three
      generation African-American family with familial GCKD is characterized. Of the 20
      individuals available for study, seven affected individuals were identified by
      renal sonogram or renal histopathology. GCKD in this family segregates as an
      autosomal dominant trait as evidenced by its apparent transmission from a father
      to his sons. A set of directed linkage strategies indicates that the distinctive
      GCKD phenotype in this family results from a dominantly acting mutation that
      disrupts a genetic locus distinct from the ADPKD loci, PKD1 and PKD2, as well the
      human homologue of mouse jcpk mutation, a newly described murine GCKD. These
      analyses are the first known genetic studies conducted in a family with heritable
      GCKD and post-infantile age of onset.

PMID- 9013452
TI  - Insulin-like growth factor (IGF) and IGF binding protein gene expression in
      multicystic renal dysplasia.
AB  - Multicystic dysplastic kidney disease is the most common form of renal dysplasia
      that leads to ESRD in children. This study describes the histopathological
      changes of multicystic dysplasia that occur from early fetal life to the
      postnatal period. At 14 wk gestation, early cystic enlargement of various
      segments of the nephron have been identified, in addition to a displaced
      metanephric blastema adjacent to zones of normal nephrogenesis. At later stages,
      the predominant features include cyst enlargement with marked fibromuscular
      collars, architectural disorganization, and replacement of the interstitium with
      a disarray of mesenchymal tissue. This study investigated the expression of the
      mRNA encoding the insulin-like growth factors (IGF) and IGF binding proteins
      (IGFBP) and have demonstrated IGF-II, IGFBP-2, and IGFBP-3 to be altered. Apart
      from their expression in the displaced metanephric blastema, both IGF-II and
      IGFBP-2 were overexpressed in abnormal tissue elements in all kidneys from fetal
      to postnatal life. IGF-II gene expression was localized to mesenchymal tissue,
      specifically in the periductal fibromuscular collars. IGFBP-2 mRNA was found to
      be expressed exclusively in the cyst epithelia of all cysts at all ages studied,
      whereas IGFBP-3 mRNA was absent from these epithelia. This study details the
      failure of normal IGF expression in the development of multicystic renal
      dysplasia and suggests a role for the IGF system in the progressive
      histopathological changes of this disorder.

PMID- 9013453
TI  - D-aspartate content of erythrocyte membrane proteins is decreased in uremia:
      implications for the repair of damaged proteins.
AB  - The authors of this article have demonstrated that erythrocytes from patients
      affected by either chronic renal failure or ESRD, conditions associated with
      erythrocyte membrane disorders, show reduced levels of methyl esterified membrane
      proteins because of elevated S-adenosylhomocysteine concentration. The enzyme
      protein L-isospartyl (D-aspartyl) O-methyltransferase, responsible for the bulk
      of this methyl esterification, is implicated in the repair of proteins containing
      isomerized and racemized aspartyl residues, which arise from L-asparaginyl and L
      aspartyl residues. The presence of these altered residues, spontaneously
      generated during protein aging, can adversely affect protein function. The amount
      of D- and L-aspartyl residues (and their isomerized derivatives) in erythrocyte
      membranes from hemodialysis patients was determined. The total level of D
      aspartyl derivatives (D-Asx) actually was found to be lower than in controls. In
      contrast, neither the abundance of several other amino acids, nor of total non
      Asx D-amino acids, differs between patients and controls. Mathematical simulation
      of relevant reactions supports the hypothesis that these effects reflect the
      lessening of the normal D-isoaspartyl residue accumulation that occurs as a side
      reaction in the methyltransferase-induced repair process. This evidence is the
      first that D-Asx content is influenced in vivo by L-isoaspartyl (D-aspartyl) O
      methyltransferase activity and can be significantly altered in a disease where
      this activity is inhibited, thus representing a red flag in a disrupted circuit.

PMID- 9013454
TI  - Utility of ultrasonography in the diagnosis of autosomal dominant polycystic
      kidney disease in children.
AB  - To determine the utility of ultrasonography (US) in diagnosing autosomal dominant
      polycystic kidney disease (ADPKD) in children, this study examined 106 children
      who were at 50% risk for the disease. The children underwent a history, physical
      examination, abdominal US, and gene linkage analysis (GLA) with tightly linked
      markers for ADPKD1 and ADPKD2 genes. Only ADPKD1 children were studied. A child
      was considered affected by US if any cysts were detected and affected by GLA if
      he or she shared the same haplotype as the affected parent. Forty-two children
      (40%) were considered to be unaffected by both GLA and US. Forty-eight children
      (45%) were considered affected by both modalities. Only two of these children had
      a single cyst. Fourteen children (13%) were considered affected by GLA with
      normal initial US. These children tended to have larger kidneys than children who
      were unaffected by GLA. Eight of these 14 children had subsequent positive
      ultrasonograms. Two children had a positive ultrasonogram with GLA showing them
      to be unaffected; in one of these children, a subsequent ultrasonogram was
      interpreted to be normal with a medullary pyramid. Thus, overall the false
      negative rate was 25%, and the false positive rate was 2%. The false negative
      rate was highest in the children who were 3 months to 5 years of age (38%).
      Clinicians must understand the utility of US in diagnosing ADPKD in at-risk
      children and must not interpret a normal study as absence of disease in this
      population.

PMID- 9013455
TI  - Predicting mortality in intensive care patients with acute renal failure treated
      with dialysis.
AB  - Existing prognostic methods were compared in their ability to predict mortality
      in intensive care unit (ICU) patients on dialysis for acute renal failure (ARF).
      The clinical goal of this study was to determine whether these models could
      identify a group of patients where dialysis would provide no benefit because of a
      near 100% certainty of death even with dialysis treatment. This retrospective
      cohort study included 238 adult patients who received a first dialysis treatment
      for ARF in the ICU. This study examined the performance of seven general ICU
      mortality prediction models and four mortality prediction models developed for
      patients with ARF. These models were assessed for their ability to discriminate
      mortality form survival and for their ability to calibrate the observed mortality
      rate with the expected mortality rate. The observed in hospital mortality was 76%
      for our patient group. Areas under the receiver operating characteristic curve
      ranged from 0.50 to 0.78. With the Acute Physiology and Chronic Health Evaluation
      (APACHE) III and the Liano models, the observed mortality in the highest
      quintiles of risk were 97% and 98%. In conclusion, although none of the models
      examined in this study showed excellent discrimination between those patients who
      died in hospital and those who did not, some models (APACHE III, Liano) were able
      to identify a group of patients with a near 100% chance of mortality. This
      indicates that these models may have some use in supporting the decision not to
      initiate dialysis in a subgroup of patients.

PMID- 9013456
TI  - Control of cytomegalovirus-associated morbidity in renal transplant patients
      using intensive monitoring and either preemptive or deferred therapy.
AB  - The objective of this randomized, prospective study was to compare preemptive to
      deferred treatment of cytomegalovirus (CMV) infection in high-risk renal
      transplant recipients. Conducted at a university-affiliated transplant center,
      the study included 36 renal allograft recipients with donor or recipient CMV
      seropositivity who received anti-thymocyte induction therapy. Ganciclovir was
      administered intravenously for 21 days upon detection of CMV viremia (preemptive,
      N = 15) or detection of CMV viremia associated with a CMV syndrome (deferred, N =
      21). Shell vial culture, conventional culture, and polymerase chain reaction
      (PCR) were performed upon buffy-coat specimens weekly for 12 to 16 wk. CMV and
      non-CMV-associated charges were calculated. The comparative sensitivities of PCR,
      shell vial culture, and conventional culture were 91%, 44%, and 47%,
      respectively. A delay in specimen processing of > 24 h severely compromised the
      sensitivity of culture techniques but not that of PCR. Preemptive therapy tended
      to decrease symptomatic CMV episodes (0.4 versus 0.6 episodes per patient
      randomized; P = 0.22). One patient in each group had organ involvement, and no
      patient died. Allograft function and survival were similar. Ganciclovir use was
      increased in the preemptive group (1.2 versus 0.6 courses per patient randomized;
      P = 0.02). CMV-associated charges were $10,368 (preemptive) versus $5,752
      (deferred); P = 0.13. PCR is superior to conventional monitoring to detect CMV
      viremia. Culture cannot be considered the "gold standard" for detection of CMV
      viremia, especially when transport of specimens over distances results in
      processing delays. Preemptive therapy may reduce symptomatic CMV infections in
      renal transplant recipients. It was associated with higher CMV-related charges
      but equivalent overall charges versus deferred treatment with intensive
      monitoring. Either strategy can achieve control of CMV infection after renal
      transplantation.

PMID- 9013457
TI  - Expression of the amiloride-sensitive sodium channel beta subunit gene in human B
      lymphocytes.
AB  - The amiloride-sensitive, epithelial sodium channel (ENaC) is composed of at least
      three subunits (alpha, beta, and gamma). This study demonstrates that the ENaC
      beta subunit gene is expressed in human B cell lines, peripheral blood
      lymphocytes, and lymph node at the mRNA level. Further, this study shows that
      both wild-type and mutated alleles of the ENaC beta subunit gene are transcribed
      in human B lymphocytes derived from an individual affected with Liddle's
      syndrome, an autosomal dominant form of human hypertension.

PMID- 9013458
TI  - Post-transplant Kaposi's sarcoma.

PMID- 9013459
TI  - HIV infection and the kidney.
AB  - HIV-infected patients may present with a variety of patterns of renal
      involvement. Acute renal failure is common and most often a result of sepsis,
      hypotension, and nephrotoxic agents. It is potentially avoidable, and support
      through the period of renal failure may lead to resolution of the renal
      dysfunction. HIV-associated nephropathy is a unique pattern of sclerosing
      glomerulopathy that ranges in prevalence from 1 to 10% of the HIV-infected
      population in different geographic locales. This complication of HIV infection
      will likely present a growing challenge to the medical community as HIV infection
      continues to spread worldwide. Deciphering the pathogenetic mechanisms of this
      most rapidly progressive form of focal segmental sclerosis is not only clinically
      relevant, but will hopefully provide valuable insights into the mediation of the
      more common idiopathic form of the disease. The potential for improved renal
      survival of patients with HIV-associated nephropathy has become more realistic
      with the development and use of antiretroviral agents, as well as studies on the
      role of immunosuppression and ACE inhibition in this population. An awareness of
      other glomerular lesion and tubulointerstitial lesions has broadened our
      understanding of populations with renal disease who have been infected by HIV.
      Moreover, as prolonged survival of HIV-infected individuals is being achieved
      with modern antiviral therapy, the percentage of patients surviving with
      nephropathy will likely grow in coming years. Awareness of the growth of this
      population and those requiring short- and long-term hemodialysis and peritoneal
      dialysis will allow appropriate planning for ESRD in the HIV-infected population.

PMID- 9013461
TI  - The winds of change.

PMID- 9013460
TI  - Micropuncture study of the mammalian urinary concentrating mechanism: evidence
      for the countercurrent hypothesis. 1959.

PMID- 9013462
TI  - Bone marrow transplant nephropathy: a case report and review of the literature.
AB  - Bone marrow transplantation can be complicated by renal failure resulting from a
      variety of causes. Early renal injury most often results from infection and its
      subsequent treatment with nephrotoxic medications. Late renal injury after bone
      marrow transplantation is characterized by a syndrome similar to the hemolytic
      uremic syndrome. This renal syndrome, called "bone marrow transplant
      nephropathy," is thought to evolve from the late effects of radiation therapy and
      cytotoxic chemotherapy on the kidney. In this article, a case of bone marrow
      transplant nephropathy and a review of the clinical and pathologic features are
      presented.

PMID- 9013463
TI  - Lymphedema the poor and benzo-pyrones: proposed amendments to the consensus
      document.

PMID- 9013464
TI  - Fluorescence microscopic studies on hemal lymph nodes in rats: a new
      immunobiological concept.
AB  - Hemal lymph nodes are characterized by a high content of blood cells most of them
      in different stages of erythrophagocytosis. These peculiar structures are not
      well understood up to now regarding their functional morphology. Above all, their
      biological relevance, especially to the phenomenon of disintegration of one's own
      blood cells, has eluded conclusive explanation so far. In the present study,
      hemal lymph nodes of 45 rats of the perirenal group were investigated by means of
      confocal laser fluorescence microscopy (CLSM) in combination with three
      fluorescent markers: latex standard particles, liposomes and autologous
      erythrocytes. Each marker briefly entered the hemal lymph nodes when injected
      into the kidney, whereas no notable migration took place after intravenous
      injection. Besides direct connections between hemal lymph nodes and the
      homolateral kidney, the study also revealed lymphatic communications with the
      contralateral kidney. Each marker was ingested by nodal macrophages, most of them
      surrounded by red blood cells (rosette formation) and laden with the by-products
      of cellular disintegration (erythrophagocytosis). Intimate contact of lymphocytes
      with macrophages as an expression of special interaction (emperipolesis) between
      both types of cells was frequently observed. A new concept is proposed, which
      ascribes to the hemal lymph nodes an important immunobiological role for the
      recognition of antigenic properties of one's own red blood cells permanently
      released by the kidney. The information macrophages obtain from these cells is
      presented to lymphocytes, which, in turn, initiates suppresser immune reactions.
      Under normal conditions, this mechanism of cellular identification and
      surveillance serves to preserve self-tolerance of the defense system against
      permanent renewal of one's own red blood cell population during a life time. In
      this way, an auto-aggressive immune anemia is circumvented.

PMID- 9013465
TI  - Combined chylous neck fistula, chylothorax and chyloperitoneum after transhiatal
      esophagectomy.
AB  - A 65-year-old man sequentially developed a chylous neck fistula, left-sided
      chylothorax, and chylous ascites after a transhiatal total esophagectomy for
      adenocarcinoma of the distal esophagus. The pathophysiology of this unusual
      accumulation of chyle in three separate anatomic compartments is examined.

PMID- 9013466
TI  - Are hemodynamic factors important in arm lymphedema after treatment of breast
      cancer?

PMID- 9013467
TI  - Visualization of the lymphatics of the heart and the mediastinal drainage
      pathways in the living cynomolgous (Macaca mulatta) monkey.
AB  - Our interest in the effects of impaired cardiac lymph drainage on coronary
      atherosclerosis led us to study the cardiac lymphatic anatomy in the monkey,
      generally considered the ideal experimental animal for examining coronary artery
      disorders. Short-term and long-term studies to visualize the cardiac lymphatic
      system and its mediastinal drainage pathways in 14 living monkeys confirmed that
      the epicardial collecting lymphatic anatomy is comparable to that of man, dog,
      and pig. These lymphatics, and particular lymphatic drainage to the cardiac lymph
      node in the right mediastinum, are difficult to visualize, in good part, because
      lymph uptake of such tracers as India Ink and T1824 blue dye is extremely slow.
      By modifying our techniques and taking cognizance of the slow lymphatic uptake of
      the tracers, we have been more successful in visualizing the mediastinal cardiac
      lymph node. Though our studies confirm that the lymphatic drainage of the monkey
      heart is similar to that in other mammals, we conclude that the "monkey model"
      has several drawbacks to study the effects of impaired cardiac lymph flow because
      of the laborious requirements to visualize successfully the cardiac lymph node.
      Perhaps the development of new markers would make this lymphatic system more
      approachable for experimental investigation.

PMID- 9013468
TI  - Primary non-Hodgkin lymphoma presenting as ileocolic intussusception.
AB  - We report the case of an HIV-seropositive patient with non-Hodgkin lymphoma of
      the small intestine who presented with an ileocolic intussusception. This lesion
      fulfilled the diagnostic criteria for primary gastrointestinal lymphoma. Such a
      neoplasm in an immuno-compromised patient is usually more aggressive and less
      responsive to treatment than in an HIV-seronegative patient.

PMID- 9013469
TI  - Autologous peripheral blood stem cells: collection and processing.
AB  - The rapid development in the area of collecting and processing autologous
      peripheral blood stem cells (PBSC) is reflected by the escalating number of
      patients treated with PBSC, and by the increasing amount of literature on the
      subject. Clinical experience suggests that among the variables with a negative
      influence on mobilization of PBSC, the most important may be the amount of
      previous stem cell toxic chemotherapy. In selecting patients suitable for
      autologous PBSC support, the requirement of an adequate anti-tumor therapy has to
      be weighed against the risk of chemotherapy related stem cell toxicity which will
      result in inability to collect a sufficient amount of PBSC. The general consensus
      is that a sufficient PBSC-autograft should contain 2-5 x 10(6) CD34+/kg body
      weight, but attempts to provide a recommended optimal or threshold level are
      hampered by the lack of standardized methods for CD34+ cell enumeration. In
      addition, the time to haematological recovery depends both on the dose of infused
      CD34+ cells and also on the amount of previous chemotherapy, which affects both
      the quality of the graft and the supportive microenvironment of the host. The
      quality of the autograft may also be contaminated by malignant cells, even if the
      biological significance of tumor cell detection in the PBSC graft has not yet
      been established. Recent development of methods for in vitro purging and
      selection of CD34+ cells for clinical use have provided the means to avoid or
      reduce reinfusion of malignant cells. Future directions of clinical research
      include the ability to define and enumerate the proportion of stem cells versus
      committed progenitor cells among the CD34+ cells in a PBSC collection, which will
      be important to ensure rapid engraftment as well as long term haematopoiesis.

PMID- 9013470
TI  - The modulation of plasma lipids and lipoproteins during bone marrow
      transplantation is unrelated to exogenously administered recombinant human
      granulocyte-monocyte colony-stimulating factor (rHu GM-CSF).
AB  - We evaluated the effect of exogenously administered recombinant human granulocyte
      macrophage colony stimulating factor (rHu GM-CSF) on plasma lipid and lipoprotein
      concentrations in 28 patients undergoing bone marrow transplantation (BMT).
      Twenty-one received rHu GM-CSF during the immediate post transplantation period
      (group 1) and seven did not (group 2). All patients received intravenous
      hyperalimentation starting at the immediate post-transplantation period until 3-5
      days post engraftment. Plasma lipids and lipoproteins, liver and renal function
      tests and blood counts were determined prior to BMT (baseline levels) and during
      the immediate and late post transplantation periods. In both groups, marked
      changes of plasma total cholesterol (TC) and high-density lipoprotein cholesterol
      (HDL-C) concentrations were observed. During the immediate post transplantation
      period, TC levels decreased by 22.2% and 26.2% in groups 1 and 2, respectively.
      During the same period, HDL-C levels decreased by 41.4% and 37.5% in these two
      groups. At the late recovery phase TC and HDL-C resumed pre-treatment levels.
      These changes were in parallel to the fluctuations in total WBC counts. We
      conclude, therefore, that BMT has a significant transient effect on plasma lipids
      and lipoproteins. Although this response is unrelated to the exogenous
      administration of rHu GM-CSF it may be causally related to endogenous cytokines
      or other, yet unidentified, factors.

PMID- 9013471
TI  - Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the
      upper gastrointestinal tract previously untreated with cytotoxic chemotherapy:
      the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293.
AB  - The aim of this study was to evaluate the clinical efficacy and safety of
      docetaxel (Taxotere) in patients with adenocarcinoma of the upper
      gastrointestinal tract previously untreated with cytotoxic chemotherapy.
      Docetaxel 100 mg m-2 was administered as a 1 hour intravenous (IV) infusion every
      3 weeks to 41 patients. Patients were premedicated prior to each course with
      dexamethasone, diphenhydramine and cimetidine. Clinical response and toxicity
      were determined. Objective responses were seen in seven of 41 eligible patients
      (two complete responses [CRs] and five partial responses [PRs], for an objective
      response rate of 17% (90% confidence interval [CI], 8% to 30%). The most common
      toxicity was grade 4 neutropenia, which occurred in 88% of patients; 46% of
      patients required a dose reduction following an episode of neutropenic fever
      requiring antibiotic therapy. Additional patients have had reversible grade 3-4
      toxicities including nausea, vomiting, stomatitis, diarrhea, fatigue and
      peripheral neuropathy. Ten patients have had grade 1-3 hypersensitivity
      reactions. Alopecia has been seen in the majority of patients. Fluid retention
      grade 1-3 has been observed in patients. Docetaxel administered on this schedule
      is an active agent in adenocarcinomas of the upper gastrointestinal tract.
      Further investigation of this drug should be conducted in multi-drug combination
      programs.

PMID- 9013472
TI  - Chronic lymphocytic leukaemia at a county hospital in southern Sweden.
AB  - We have studied retrospectively patients with chronic lymphocytic leukaemia
      (CLL), at Ryhov, Jonkoping, Sweden during a 10-year-period. This unselected
      cohort (n = 59) from a well-defined geographical area is suitable for describing
      the natural course of the disease. The CLL was diagnosed incidentally in the
      majority of cases. Median-age at diagnosis was 71 years and the male:female ratio
      was 1.3:1. The diagnosis was based on morphology in 66% and in 33%
      immunophenotyping specified the diagnosis of B- or T-CLL. At diagnosis 66% were
      in Rai-stage O/I or Binet-stage A. There were 36% untreated patients and their
      median-survival was 108 months compared with 84 months for the whole cohort and
      72 months for the treated patients. Malignancies were seen in 31% and infections
      in 83%. Intercurrent diseases played an important role in the survival. During
      the observation time, only 54% of the deceased patients had died due to the CLL.

PMID- 9013474
TI  - Phase II trial of docetaxel (Taxotere) in patients with metastatic melanoma
      previously untreated with cytotoxic chemotherapy.
AB  - A phase II study was undertaken to evaluate the clinical efficacy and safety of
      docetaxel in patients with malignant melanoma. Between April 1992 and February
      1996, 37 patients with metastatic malignant melanoma and no prior chemotherapy
      were treated with docetaxel 100 mg m-2 administered intravenously over 1 hour
      every 21 days. Patients were premedicated prior to each course with dexamethasone
      and diphenhydramine. Toxicity and follow-up were provided. Objective responses
      were seen in two out of 35 patients evaluable for response, one complete response
      and one partial response. These two responses were of a duration of greater than
      two years. The most common toxicity was grade 4 neutropenia, which occurred in
      92% of patients; 49% required hospitalization for an episode of neutropenic
      fever. Additional patients had reversible grade 3-4 toxicities including nausea,
      vomiting, diarrhea, stomatitis, arthralgias, myalgias, peripheral neuropathy and
      fatigue. Eighteen patients had hypersensitivity reactions, two were grade 3-4.
      Fluid retention, grade 1-3 was observed in seven patients. Alopecia occurred in
      most patients. Docetaxel has definite but low-level activity against malignant
      melanoma. Further investigation of this drug should be considered in multidrug
      combination programs.

PMID- 9013473
TI  - Mechanistic analysis of high antitumor effect of intradermal administration of
      lipopolysaccharide from Pantoea Agglomerans.
AB  - Lipopolysaccharide from Pantoea Agglomerans (LPSp) has a remarkably high
      antitumor activity even against poorly immunogeneic tumors when given by
      intradermal injection combined with cyclophosphamide (CY). We have extended this
      study to gain an insight into the mechanism of this antitumor effect, and
      especially into the induction of cell mediated immunity. In immunohistological
      studies, extensive necrosis and marked infiltration of the inflammatory cells at
      the tumor were observed after intradermal injection of LPSp combined with CY, but
      not after CY alone or after no treatment. The cells around the tumors were mostly
      neutrophils and macro phages (Mac 1+); T cells (CD4+, CD8+) were also present.
      The serum levels of cytokines, induced after intradermal injection of LPSp, were
      determined and compared with intravenous administration of LPSp or recombinant
      TNF-SAM2. TNF-alpha, IL-1, IL-6 and GM-CSF were measured by ELISA as a marker of
      cytokine induction. The peak level of TNF-alpha induced by intradermal injection
      of LPSp was about 5000 pg ml-1, which was considered relatively small since this
      level was observed even in clinical trial. There seems to be a longer period of
      release of TNF-alpha after an intradermal injection than after an intravenous
      injection. This may produce the remarkably high antitumor effect of the
      intradermal injection. The antitumor effect of intradermal administration
      combined with CY was evaluated in nude mice to clarify the role of T cells in
      high antitumor activity. In this experiment, antitumor activity was found to be
      much less in BALB/c nu/nu mice without regression, while complete regression was
      frequently observed in syngeneic mice, showing the crucial role of T cells in
      this treatment. These observations suggest that intradermal administration of
      LPSp in combination with CY continuously releases and induces not only extensive
      necrosis of the tumor but also cell mediated antitumor immunity, which may be
      indispensable for complete regression of the tumor. Clinical application of this
      treatment for advanced cancer patients is in progress.

PMID- 9013475
TI  - Burkitt-like blast crisis in chronic myeloid leukemia.
AB  - A case of Burkitt-like blast crisis in a patient with chronic myelocytic
      leukaemia (CML) is presented. To our knowledge, this is the first such case
      recorded to date. The patient had a useful response to combination chemotherapy.

PMID- 9013477
TI  - Constitutional alterations in p16 in patients with uveal melanoma.
AB  - Chromosome 9p21 contains a susceptibility gene for cutaneous melanoma. Recent
      studies suggest that the gene responsible may be CDK41, since it encodes a
      putative cell cycle inhibitor, p16, and is frequently lost or rearranged in
      melanoma cell lines. In this study we examined whether germline alterations in
      CDK41 could be identified in patients with melanoma of the uveal tract. From an
      archive of bloods collected from patients with uveal melanoma, we identified 13
      samples drawn from patients with a history in a family member of uveal (n = 6) or
      cutaneous (n = 7) melanoma. An additional 24 'control' bloods (without melanoma
      or any other primary malignancy in a family member), similar to the 'cases' in
      age and number of first-degree relatives, were also selected for study. For each
      sample, DNA was extracted from the red blood cell fraction. Using the polymerase
      chain reaction-single strand conformation polymorphism method, we screened for
      alterations in p16. Specific changes were characterized by DNA sequencing. Six
      nucleotide changes were detected in five (13.5%) of the 37 samples examined. An
      altered gene was found in one (7.7%) of the 13 patients with a family history (of
      intra-ocular melanoma) and four (16.7%) of the 24 patients with no family history
      (P = 0.64) of melanoma. In this series the group with a positive family history
      was predominantly female and most pedigrees involved matrilineal descent. In
      these data prevalence of germline alteration in p16 was similar in familial and
      sporadic cases. The results provide evidence against a significant role for p16
      in familial clustering of intra-ocular and cutaneous melanomas.

PMID- 9013478
TI  - HNK-1 antigens on uveal and cutaneous melanoma cell lines.
AB  - The HNK-1 epitope has been associated with the metastatic behaviour of uveal
      melanomas. We characterized HNK-1 antigens on four human uveal (primary and
      metastatic) and two primary cutaneous melanoma cell lines by immunocytochemistry
      and Western blot analysis. We also determined the involvement of the HNK-1
      epitope in cell-cell interactions on a matrigel layer. Three uveal melanoma cell
      lines (one primary and two metastatic) and one cutaneous melanoma cell line
      showed HNK-1 expression by immunocytochemistry. On matrigel, only the HNK-1
      positive cutaneous melanoma cell line Bowes grew in a honeycomb-like structure
      which disappeared after adding HNK-1 antibodies to the culture medium. Immunoblot
      analysis of the primary uveal melanoma cell line EOM-3 revealed five HNK-1
      positive protein bands with apparent molecular weights of 200, 160, 115, 95 and
      75 kDa. The cutaneous melanoma cell line Bowes showed three HNK-1-positive
      protein bands with apparent molecular weights of 150, 135 and 90 kDa. This study
      shows that two uveal (primary and metastatic) and one primary cutaneous melanoma
      cell lines express HNK-1 antigens on immunoblot. Only in the HNK-1-positive
      cutaneous melanoma cell line Bowes did the HNK-1 epitope have a function in
      intercellular adhesion. Although the primary uveal melanoma cell line EOM-3
      showed a similar HNK-1 immunoreactivity, we could not demonstrate HNK-1-mediated
      cell adhesion. On immunoblot, the two cell lines displayed different HNK-1
      antigens, which may explain the difference in cell adhesion.

PMID- 9013476
TI  - Detection of minimal residual disease in multiple myeloma and acute leukaemia.
AB  - The importance of minimal residual disease detection has increased due to the
      advanced therapeutic protocols available for multiple myeloma and acute
      leukaemia. High-dose chemotherapy, followed by stem cell transplantation is often
      used in patients with multiple myeloma. But despite a longer disease-free period
      and overall survival, all patients relapse. In the treatment of acute leukaemia,
      there are similar problems. The present strategy is to give continuous
      chemotherapy to eradicate minimal residual disease. In this review, we consider
      the methods used to detect and quantify minimal residual disease. At present, the
      most effective seem to be those based on the use of polymerase chain reactions to
      detect the malignant cells.

PMID- 9013480
TI  - Enhanced effects of multiple treatment electrochemotherapy.
AB  - Electrochemotherapy has been demonstrated to be an effective treatment for
      cutaneous cancers. The treatment includes administering a chemotherapeutic agent
      followed by electric pulses which are applied directly to the tumour. The pulses
      facilitate delivery of drug through the plasma membrane. Enhanced delivery is
      restricted to the area that has been electrically treated. Currently,
      electrochemotherapy is administered as a single treatment. Complete response
      rates are high; however, partial responses are obtained in a fraction of the
      treated tumours. An issue associated with this is whether or not multiple
      treatments would result in an improved therapy for these partially responding
      tumours. A multiple treatment electrochemotherapy study was implemented in order
      to address this issue. The study utilized subcutaneously induced murine B16
      melanoma tumours in C57B1/6 mice. Results showed large tumour volume reductions
      in multiple treatment groups. In addition, a twofold increase in tumour doubling
      time and greater percentages of complete responses were found as a result of
      multiple treatment. These results will be utilized to augment existing clinical
      trials with respect to retreating tumours that have partially responded to a
      single electrochemotherapy treatment.

PMID- 9013479
TI  - Cytolytic T cell reactivity against melanoma-associated differentiation antigens
      in peripheral blood of melanoma patients and healthy individuals.
AB  - Antigenic peptides derived from several differentiation antigens of the
      melanocyte lineage were recently identified in human melanomas as targets for HLA
      A2.1-restricted cytotoxic T lymphocytes (CTLs). To examine their potential role
      in tumour-directed immune responses in vivo, we determined CTL reactivity against
      seven antigenic peptides derived from the Melan A/MART-1, tyrosinase and
      gp100/Pmel17 antigens in the peripheral blood of 10 HLA-A2+ healthy controls and
      26 HLA-A2+ melanoma patients. The influenza matrix peptide (GILGFVFTL) presented
      by HLA-A2.1 was used as a control peptide. CTL reactivity was assessed in a mixed
      lymphocyte 'peptide' culture assay. Reactivity against Melan A/MART-1-derived
      peptide antigens was readily detectable in both melanoma patients and controls.
      Reactivity directed against tyrosinase-derived peptide antigens was also detected
      in both melanoma patients and healthy individuals, but less frequently. A
      measurable response against gp100/Pmel17-derived antigens was found in 1/10
      controls and in 1/26 of the melanoma patients. Reactivity against the influenza
      matrix peptide was common in both melanoma patients and controls. Our findings
      show that precursor CTLs against melanocyte differentiation antigens can be
      detected in peripheral blood of melanoma patients and healthy individuals. The
      pattern of CTL reactivity directed against melanoma-associated antigens does not
      seem to be altered in melanoma patients. Despite antigen-specific CTL reactivity,
      tumour growth was not prevented in melanoma patients and autoimmune phenomena
      were not detected in healthy individuals. It remains to be determined whether
      precursor CTLs recognizing melanocyte differentiation antigens can be activated
      by immunization and lead to effective tumour rejection in vivo.

PMID- 9013481
TI  - Cutaneous malignant melanoma in women is uncommonly associated with a family
      history of melanoma in first-degree relatives: a case-control study.
AB  - Sun exposure is the principal cause of malignant melanoma, but other risk factors
      may be important. During their reproductive years women are at a greater risk for
      melanoma than men. We performed an age-matched case-control study of cutaneous
      malignant melanoma in 159 women attending a single oncology clinic in Montreal. A
      reported family history of cutaneous malignant melanoma in first-degree relatives
      was associated with a significantly increased risk of melanoma (adjusted relative
      risk: 4.28, P = 0.046). No subject was a member of a hereditary melanoma family
      (three or more cases of melanoma in first-degree relatives). As expected,
      variables related to sun exposure were also strong determinants of risk. Height
      was a significant risk factor, but the difference between the mean heights of
      cases and controls was only 2 cm (P = 0.009). The age of menarche of cases was
      lower than in controls (mean 12.70 and 13.08 years respectively, P = 0.036) but
      there was no significant elevation in risk associated with other reproductive
      variables. This study suggests that a family history of malignant melanoma is a
      significant risk factor, but that hereditary melanoma may be less common than is
      currently believed.

PMID- 9013482
TI  - Apparent anticipation in familial melanoma.
AB  - Genetic anticipation refers to progressively earlier age at diagnosis (AAD)
      and/or increasing severity of a disorder in successive generations. Previous
      examination of 23 familial melanoma kindreds revealed evidence for a dramatic
      reduction in AAD in successive generations. To further evaluate evidence for
      anticipation, we examined the AAD, number of tumours, and tumour thickness in
      affected parent-offspring (P-O) pairs from these 23 kindreds. Number of tumours
      and tumour thickness were also evaluated by generation. There were statistically
      significant intergenerational differences for AAD and number of tumours in the 47
      affected P-O pairs. Median AAD decreased from 48 years to 28 years. The median
      AAD in the offspring (AADo) of a parent with CMM (median 28, mean 29.3 +/- 10.1
      years, n = 51) was significantly different from the median AADo of a parent
      without CMM (42, 42.3 +/- 13.9 years, n = 55) (P < 0.001). In addition, parents
      with AAD less than the median of 48 years had offspring with a median AAD (26,
      25.8 +/- 8.5 years, n = 21) significantly different from those of parents with
      AAD > or = 48 years (32, 34.5 +/- 10.2 years, n = 26) (P = 0.005). Ninety-four
      percent (44/47) of the P-O pairs showed positive anticipation, with 62% showing
      anticipation of > 15 years. There was little difference based on the affected
      parent's sex. In the 106 CMM cases there were no significant differences in
      tumour number (P = 0.08) or tumour thickness (P = 0.85) by generation. Number of
      tumours was however significantly different in cases with AAD < 34 years (n = 52,
      median 1.5, mean 2.3 +/- 2.4) vs cases with AAD > or = 34 years (n = 54, 1.0, 1.6
      +/- 1.7) (P < 0.001). Thus these 23 familial melanoma kindreds showed evidence
      for anticipation as defined by a decrease in AAD in successive generations.
      Although increased surveillance may partly explain the results, additional
      studies should evaluate melanoma risk factors, genetic and/or environmental,
      across generations to examine the reasons for the apparent anticipation.

PMID- 9013483
TI  - International Conference on the Biology of Melanoma. Aviano, Italy, 24-26
      September 1995.

PMID- 9013484
TI  - DNCB for local control of malignant melanoma: don't forget a winning horse!

PMID- 9013485
TI  - The lectin pathway of the complement system.

PMID- 9013486
TI  - Serological survey of spotted fever group rickettsia in wild rats in Thailand in
      the 1970s.
AB  - In Thailand, the first human cases of spotted fever group rickettsiosis were
      reported in 1994, but no serosurveys on wild rats have yet been conducted. We
      investigated the seroepidemiology in wild rats collected in the 1970s from two
      regions in Thailand, and found a 62.2% positive rate of antibodies for spotted
      fever group rickettsia (SFGR) by the indirect immunofluorescence antibody test.
      Of the antibody-positive rats, 82.2% had higher titers of antibodies against TT
      118 than those against Rickettsia japonica, which suggests that Thailand is
      infested mainly with the TT-118 strain or its antigenically related organisms.
      The prevalence of antibodies in Bandicota indica was significantly higher than
      that in other species, which suggests that B. indica is important as a reservoir
      of SFGR in Thailand.

PMID- 9013488
TI  - Induction of tumor necrosis factor alpha (TNF alpha) and enhancement of HIV-1
      replication in the J22HL60 cell line by Mycoplasma penetrans.
AB  - Mycoplasma penetrans isolated from clinical specimens of AIDS patients showed
      potent activity in tumor necrosis factor alpha (TNF alpha) production in THP-1,
      U937 and J22HL60 cell lines, and in the enhancement of HIV-1 replication in a
      dormantly-infected J22HL60 cell line as compared with the activities of other
      mycoplasmas. Both activities were found in the methanol layer but not in the
      chloroform layer of the membrane extracted by the Bligh-Dyer method. TNF alpha
      production was observed in the peritoneal macrophages from both
      lipopolysaccharide-responsive and -unresponsive mouse strains, and was not
      inhibited by polymyxin B. The induction of TNF alpha production and enhancement
      of HIV-1 replication were strongly inhibited by Concanavalin A-Sepharose. The
      inhibitory effect of Concanavalin A-Sepharose was partially prevented by sugars
      in the order methyl-alpha-D-mannopyranoside and methyl-alpha-D-glucopyranoside
      but not methyl-alpha-D-galactopyranoside. Anti-human TNF alpha antibody, however,
      did not reduce the activity of the methanol layer to enhance HIV-1 replication,
      suggesting that the methanol layer could enhance HIV-1 replication directly.
      These results suggest that the carbohydrate derived from M. penetrans might be
      responsible for the progression of HIV-1 infection.

PMID- 9013487
TI  - Rapid increase of pneumococcal resistance to beta-lactam and other antibiotics in
      isolates from the respiratory tract (Nagasaki, Japan: 1975-1994).
AB  - The susceptibility of 101 pneumococcal isolates from the respiratory tract during
      1991-1994 was examined and compared with the susceptibility of isolates over the
      period of 1975-1990. A rapid increase of resistance was seen not only to
      penicillin but also other antimicrobial agents. During 1991-1994, 38% of all the
      isolates were resistant to penicillin. The rates of resistance during this period
      were 16-23% for three newer cephalosporins, 18% for imipenem, 69% for
      tetracycline, 31% for erythromycin, 20% for chloramphenicol and 9% for
      clindamycin. The use of antibiotics within one month prior to pneumococcal
      isolation was correlated with penicillin resistance (P < 0.05). Serotyping of the
      isolates by antiserum revealed differences in predominant types between
      penicillin-resistant (19F, 23F,4) and -susceptible isolates (15, 4, 11A). Our
      data suggests that anti-pneumococcal antibiotics should be carefully chosen on
      the basis of susceptibility tests.

PMID- 9013489
TI  - Re-speciation of the original reference strains of serovars in the Citrobacter
      freundii (Bethesda-Ballerup group) antigenic scheme of West and edwards.
AB  - The antigenic scheme for the Bethesda-Ballerup group of bacteria established by
      West and Edwards in 1954 has continued to be applied as a serotyping scheme for
      Citrobacter freundii. In 1993, however, the classification of the Citrobacter was
      drastically revised and the species C. freundii redefined by Brenner et al.
      Accordingly, to judge the propriety to continuously use a single antigenic scheme
      for the C. freundii complex, the 90 reference strains listed in the antigenic
      scheme for C. freundii by West and Edwards were characterized phenotypically and
      specified based on the revised classification. Of these 90 strains, two strains
      of Hafnia alvei and one of Escherichia coli were found. Among the remaining 87
      reference strains, Citrobacter youngae was the predominant species (40 strains),
      followed by Citrobacter braakii (25 strains), Citrobacter werkmanii (13 strains),
      and the unnamed Citrobacter genospecies 10 of Brenner et al (six strains).
      Citrobacter freundii, as redefined, accounted for only three strains and ranked
      behind the other four species. No overlapping with most of the 42 O-groups and 82
      H-antigens was recognized between species with few exceptions. O-groups 1-9
      inclusive, which were estimated to represent more than 90% of the former
      C.freundii strains, occurred in strains of C. youngae and C. braakii; and all
      nine strains of O-group 29, formerly known as the Ballerup group, were identified
      as C. braakii. These findings suggest that further study of the serotyping system
      is needed for all H2S-producing Citrobacter species.

PMID- 9013490
TI  - Expression of the colH gene encoding Clostridium histolyticum collagenase in
      Bacillus subtilis and its application to enzyme purification.
AB  - The colH gene encoding 116-kDa collagenase of Clostridium histolyticum (cColH)
      was cloned into an Escherichia coli-Bacillus subtilis shuttle vector to develop a
      method for purification of recombinant collagenase (rColH). When plasmid pJCM310
      containing the colH gene was introduced into B. subtilis DB104 and the
      transformant was grown in LB broth at 37 C, stability of the plasmid was not
      maintained. However, stability was partly improved by growing the transformant in
      a modified LB broth containing 0.5 M sodium succinate with gentle shaking at 35
      C. When the transformant was grown to an optical density of 0.4 at 600 nm in this
      medium, pJCM310 was stable and rColH was produced in sufficient amounts. rColH
      was purified to homogeneity by ammonium sulfate precipitation, gel filtration and
      ion-exchange chromatography. The yield of rColH from an 800-ml culture was 0.53
      mg and its specific activity was estimated to be 1,210 U per mg of protein. The
      purified rColH was capable of degrading native type-I collagen fibril from bovine
      achilles tendon, as was demonstrated by zymography. A comparison of the N
      terminal amino acid sequence between cColH and rColH revealed that rColH has 10
      extra N-terminal amino acid residues. However, the peptide mapping of rColH with
      V8 protease was virtually identical to that of cColH. Furthermore, the molecular
      mass of rColH was estimated to be 112,999 Da by mass spectrometry, coinciding
      with the value of 112,977 Da, which was predicted from the nucleotide sequence of
      the colH gene. Therefore, the recombinant B. subtilis culture is capable of
      serving as a useful source for enzyme purification.

PMID- 9013491
TI  - Effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on
      biomaterial-associated staphylococcal infection in mice.
AB  - Staphylococcal infections are a major complication in the usage of biomaterials.
      Different modifications of polymers have been made to reduce the incidence of
      such infections. We studied the effects of modifying heparinized polyethylene (H
      PE) with mouse recombinant granulocyte-macrophage stimulating factor (rGM-CSF).
      The elimination of staphylococci (Staphylococcus aureus, S. epidermidis) from the
      peritoneum of mice implanted with rGM-CSF-coated H-PE was slightly more effective
      than the elimination of the bacteria from the peritoneum of animals implanted
      with uncoated H-PE. Most interestingly, the number of staphylococci present in
      the biofilms covering rGM-CSF-coated implants were significantly lower than the
      number of bacteria detected on the surface of H-PE not coated with rGM-CSF. In
      vitro, rGM-CSF restored the anti-bacterial potency of the phagocytes, which had
      been reduced by surface contact with H-PE. The results suggest that modification
      of biomaterials with rGM-CSF could be one way of preventing staphylococcal
      infections; especially in neutropenic disorders, which constitute the highest
      risk factor for foreign body-associated infections.

PMID- 9013492
TI  - Sequence variation of the hypervariable region in HCV carriers with normal ALT
      levels: a comparison with symptomatic carriers.
AB  - The clinical significance of the hypervariable region (HVR) in the N-terminus of
      the E2/NS1 region, which encodes the putative envelope glycoprotein (gp 70) of
      HCV, has not yet been elucidated. We studied the relation between HVR changes and
      elevation of the alanine aminotransaminase (ALT) level due to liver cell injury
      as well as the persistence of HCV infection. Three patients (carrier group) who
      were HCV RNA positive and had normal ALT levels for as long as five years and
      three patients with high ALT levels were studied. None of the six patients had a
      history of treatment. HCV RNA was extracted from serum obtained from each patient
      in 1990 and 1995. The E2/NS1 region, including HVR-1 and HVR-2, was amplified
      using the RT-PCR method. PCR products were cloned and nucleotide sequences were
      determined using the dideoxynucleotide chain termination method. No clear
      correlation was found between the ALT levels and the number of nucleotide
      substitutions in HVR-1. The number of nucleotide substitutions in HVR-1 during
      the five years was greater than in other regions. Furthermore, more nucleotide
      substitutions occurred in the 1st and 2nd codon positions of HVR-1 than in the
      control region, even in the carrier group. In conclusion, HVR-1 changes are
      probably a more important factor in persistent viral infection than liver cell
      injury.

PMID- 9013493
TI  - The UL2 open reading frame of bovine herpesvirus 1 encodes a uracil-DNA
      glycosylase.
AB  - Sequence analysis within the unique long segment of the bovine herpesvirus 1 (BHV
      1) genome previously identified an open reading frame (ORF), designated UL2,
      whose deduced polypeptide of 204 amino acids contained a consensus uracil-DNA
      glycosylase (UDGase) signature sequence. To determine whether the BHV-1 UL2 ORF
      product has UDGase activity, we positioned the UL2 sequence down-stream of the T7
      promoter on the vector pET-28b(+) and expressed it in Escherichia coli. Upon
      induction with isopropyl beta-D-thiogalactopyranoside these cells produced a 23
      kDa protein, the molecular mass of which was in accordance with the prediction
      from the nucleotide sequence. A one-step purification procedure using nickel
      chelating affinity chromatography resulted in a homogeneous preparation of this
      protein, which displayed specific UDGase activity in an in vitro enzyme assay.
      These results provide evidence that the BHV-1 UL2 gene does encode a UDGase.

PMID- 9013494
TI  - The TNF-ligand and receptor superfamilies: controllers of immunity and the Trojan
      horses of autoimmune disease?
AB  - This review is concerned with the tumour necrosis factor receptor and ligand
      superfamilies, with particular reference to their roles in the immunopathogenesis
      of Systemic Lupus Erythematosus (SLE). The tumour necrosis factor receptor and
      ligand superfamilies are well characterized as the molecular controllers of the
      immune system, acting as 'judges', 'juries', and, where necessary, 'executioners'
      to determine the fate of immune cells during development, proliferation and
      differentiation. However, these molecules exert extreme immunopathological
      effects when unregulated, or dysfunctional. The importance of these molecules in
      the pathogenesis of autoimmunity is now apparent, and has been considered in
      detail. Finally, specific consideration has been given to their clinical
      significance and potential diagnostic and therapeutic applications.

PMID- 9013495
TI  - The role of the hypothalamic-pituitary-adrenocortical axis in memory-related
      effects of anxiolytics.
AB  - Two major classes of antianxiety drugs, benzodiazepines and partial agonists of 5
      HT1A receptors, have dissimilar effects on learning. Benzodiazepines induce
      amnesic effects in humans and animals. In contrast, partial agonists of 5-HT1A
      receptors do not suppress memory in humans and have variable effects in animal
      learning models. The two groups of drugs shift activity of the hypothalamic
      pituitary-adrenocortical (HPA) axis in opposite ways. Benzodiazepines, given at
      antianxiety doses, suppress HPA axis excitability. Partial agonists of 5-HT1A
      receptors facilitate HPA excitability and, at higher doses, directly stimulate
      ACTH secretion. Assuming that certain components of the HPA axis are involved in
      memory acquisition, it is hypothesized that antianxiety drugs may affect learning
      through the regulation of HPA axis excitability.

PMID- 9013496
TI  - Antibody to day-old chick brain glycoprotein produces amnesia in adult rats.
AB  - Polyclonal antibody R-1, raised against a chick synaptic membrane glycoprotein
      fraction whose synthesis is enhanced following training on a passive avoidance
      task, produces amnesia when injected into chick forebrain 5.5 h posttraining. The
      amnestic IgG fraction specifically recognizes a low sialylated isoform of NCAM
      (Mileusnic Rose, Lancashire, & Bullock, 1995). We have now investigated the
      effects of this antibody on memory formation in adult rats. R-1, preimmune serum,
      or saline was injected intracerebroventricularly 5.5 h posttraining through
      bilaterally implanted cannulae. Rats injected with R-1 and tested 48 h later
      showed a significant amnesia for avoidance compared with the controls. Amnesia
      was not apparent at 24 h posttraining. R-1 injections were without effect on
      spontaneous locomotor or exploratory activity in a holeboard test. The results
      contribute to the argument that the role of cell adhesion molecules in neuronal
      plasticity is not limited to the developing nervous system, but they play a more
      general role in the experience-dependent synaptic remodeling underlying long-term
      memory.

PMID- 9013497
TI  - Postoperative environmental enrichment attenuates fimbria-fornix lesion-induced
      impairments in Morris maze performance.
AB  - Male Wistar rats were given a bilateral or a unilateral transection of the
      fimbria-fornix; subsequently they were kept in standard laboratory housing
      conditions or in enriched environments for 6 weeks, after which they were tested
      in the Morris maze. In the acquisition phase of the experiment rats with a
      bilateral lesion of the fimbria-fornix were markedly impaired in their ability to
      locate the hidden platform, while rats with unilateral lesions displayed no such
      impairment. However, rats with a bilateral lesion displayed a less severe deficit
      when they had been housed postoperatively in the enriched environment. In the
      retention phase of the experiment rats with a bilateral lesion swam markedly less
      time in the platform zone only when they had been housed in standard conditions.
      They also spent more time in the edge zone than the other groups. Rats with a
      bilateral lesion that were housed enriched did not swim more in the edge zone.
      Despite their good performance during acquisition they did not display a clear
      preference for the platform zone. Thus, it was speculated that enriched rats with
      a bilateral lesion had learned to leave the side of the pool to search for the
      platform and with the aid of this different strategy improved their performance.

PMID- 9013498
TI  - Learning-dependent dendritic hypertrophy of cerebellar stellate cells: plasticity
      of local circuit neurons.
AB  - Recent work has shown that motor learning, but not mere motor activity, changes
      the morphology of Purkinje cells, the major projection neurons of the cerebellar
      cortex. In the present study we examined how motor skill learning affects the
      dendritic morphology of the stellate local circuit neurons. Adult female rats
      were either trained to complete a complex motor learning task or forced to
      traverse a flat, obstacle-free runway. Golgi impregnated stellate cells were then
      traced via camera lucida and their dendritic arborizations examined with a
      concentric ring analysis. Results showed the motor learning animals to have
      significantly greater stellate cell dendritic arborizations than the activity
      controls. Thus these local circuit neurons exhibit morphological plasticity.

PMID- 9013500
TI  - Effects of postoperative housing conditions on functional recovery in rats with
      lesions of the hippocampus, subiculum, or entorhinal cortex.
AB  - In order to study the effects of differential housing conditions on recovery from
      damage to different components of the hippocampal formation, 85 rats received
      bilateral lesions of the hippocampus, entorhinal cortex, or subiculum or sham
      surgery and then were housed for 30 days in either an enriched environment or an
      impoverished environment. Rats were subsequently tested on a battery of tasks for
      assessing locomotor activity in their home cage, reactivity to novelty, spatial
      working and reference memory in the Morris water maze, and learning in the Hebb
      Williams maze. Rats with the hippocampus removed showed impairments in most of
      the tasks we used (home-cage and novelty-induced locomotor activity, water maze,
      and Hebb-Williams maze). Most of the deficits induced by lesions to the
      entorhinal cortex were similar to those induced by the removal of the
      hippocampus. Some differences appear to be among the deficits induced by the
      lesions of these structures when assessing the home-cage locomotor activity, the
      reactions to novelty, and one aspect of the Hebb-Williams maze learning. Lesions
      to the subiculum induced only an impairment in the probe trial of the water-maze
      task. Confirming and extending previous findings in rats with various (but
      nonexcitotoxic) lesions of the hippocampus, an enriched environment had a
      beneficial effect on several of the deficits observed in the tasks we used.
      Further, only the rats with hippocampal lesions benefitted from having been
      housed in the enriched environment. However, their facilitated recovery was not
      observed in all tasks. After damage to different components of the hippocampal
      formation, the beneficial effects induced by the enriched housing conditions were
      shown to be both lesion-locus- and task-dependent.

PMID- 9013499
TI  - Olfactory conditioning impairment following posttraining NMDA receptor blockade
      in neonatal rats.
AB  - Six-day-old Sprague-Dawley rat pups were exposed to peppermint odor paired with
      tactile stimulation (stroking the skin with a paint brush) for twenty 10-s
      conditioning trials, and their olfactory preference was tested the next day. In
      Experiment 1, pups that had received an injection of the noncompetitive N-methyl
      D-aspartate receptor antagonist MK-801 (0.1 mg/kg, i.p.) either 30 min before or
      immediately after conditioning spent less time over the conditioned odor than
      saline-treated controls. In Experiment 2, pups received an injection of either MK
      801 or saline 0, 30, or 60 min after the training period. There was a reduction
      in the preference for the conditioned odor in the animals receiving MK-801
      immediately following training, but treatment with the drug at the other
      intervals did not produce a performance impairment. The impairment following
      immediate posttraining injection occurred with either 0.05 or 0.1, but not with
      0.01 mg/kg of MK-801 (Experiment 3). Experiment 4 provided control data to
      confirm that pups that had experienced the procedures used in Experiments 1-3
      showed greater preference for the conditioned odor than did naive pups or those
      receiving exposure to the odor without stroking. The data indicate that immediate
      posttraining activation of N-methyl-D-aspartate receptors is required for normal
      olfactory learning in neonatal rats.

PMID- 9013501
TI  - Insular cortex and amygdala lesions induced after aversive training impair
      retention: effects of degree of training.
AB  - These experiments examined the effects of N-methyl-D-aspartate (NMDA)-induced
      lesions of the amygdala and insular cortex induced 1 week after rats were trained
      on a footshock motivated escape task in a two-compartment runway. In the first
      experiment, male rats were given 10 training trials and, 1 week later, received
      microinjections of a buffer solution or NMDA into either the insular cortex (IC)
      or the amygdala (AM). In an inhibitory avoidance retention test 1 week after the
      microinjections, the retention latencies (i.e., latencies to enter the
      compartment where shock had been delivered) of both the AM- and "IC-lesioned"
      groups were significantly lower than those of the buffer-injected groups.
      Additionally, in comparison with the buffer controls, rats in the two lesioned
      groups made significantly more crossings between the two compartments during the
      retention test. In a second experiment, male rats were given 1, 10, or 20 escape
      training trials 1 week before receiving either sham or NMDA lesions in the IC.
      The retention test was given 1 week after microinjection. Those sham or lesioned
      animals that were given only one training trial did not demonstrate retention.
      Both lesioned groups given 10 or 20 training trials were significantly disrupted
      on both the step-through latencies, and the number of crossings between the two
      compartments. The retention-impairing effects of NMDA-induced lesions were
      slightly attenuated in the group given 20 escape training trials. The findings
      provide additional evidence that the AM and the IC are involved in regulating the
      long-term retention of aversively motivated training.

PMID- 9013502
TI  - Evidence for spinal conditioning in intact rats.
AB  - Prior work suggests that spinal systems are sensitive to the stimulus
      relationships that underlie Pavlovian conditioning. We studied this phenomenon in
      Sprague-Dawley rats by pairing a vibrotactile conditioned stimulus (CS) with a
      tailshock unconditioned stimulus (US). Experiment 1 showed that spinal rats
      exhibit differential conditioning, having longer tail-flick latencies on the tail
      flick test during a CS that was paired with the US (conditioned antinociception).
      Experiment 2 showed that rats trained with the cord intact still exhibit
      differential conditioning after the cord is cut. This suggests that spinal
      learning contributes to behavioral plasticity in intact subjects.

PMID- 9013503
TI  - Enhancement of intermediate-term memory by an alpha-1 agonist or a partial
      agonist at the glycine site of the NMDA receptor.
AB  - The aim of the present study was to investigate whether the activation of alpha-1
      adrenergic receptors can influence intermediate-term memory. Therefore, the
      effects of ST 587 (30 or 100 micrograms/kg), a putative alpha-1 agonist, on the
      retention of the radial arm task using non-matching to sample with a 4-h delay
      were investigated in rats. The results indicated that the administration of ST
      587 (100 micrograms/kg) before a sampling phase increased the time to complete
      the sampling phase which was due to an increased number of errors of repetition
      (regarded as working memory errors) and a reduced number of arms visited in a
      given time (regarded as behavioral activity). However, this treatment increased
      the number of correct choices before the first error during the retention phase
      in this task. Since we were also interested in investigating the role of NMDA
      receptors in memory encoding, we investigated whether NMDA receptor modulation by
      d-cycloserine (1 or 10 mg/kg), a partial agonist of the glycine site on the NMDA
      receptor, had any influence on the performance of rats in this task. The results
      indicated that d-cycloserine (10 mg/kg) given before the sampling phase did not
      influence the performance of rats during the sampling phase, but it did improve
      their choice accuracy during the retention phase of this task. These data suggest
      that the systemic administration of either an alpha-1 agonist or an indirect
      agonist of NMDA receptors can facilitate intermediate-term retention of spatial
      information.

PMID- 9013504
TI  - Type II glucocorticoid receptor antagonists impair contextual but not auditory
      cue fear conditioning in juvenile rats.
AB  - There is evidence that glucocorticoids may play a role in learning and memory. To
      further explore this possibility, we examined the effect of the Type II
      glucocorticoid antagonists on contextual fear conditioning. This conditioning
      task is dependent on the hippocampal formation, a brain structure known to be
      rich in glucocorticoid receptors. Rats systemically injected with a Type II
      antagonist either 1 h prior to conditioning (RU 38486 and RU 40555) or
      immediately after conditioning displayed less contextual fear conditioning than
      rats injected with vehicle. Although RU impaired contextual fear conditioning, it
      had no effect on auditory fear conditioning. These data are consistent with other
      reports that contextual fear conditioning and auditory-cue fear conditioning
      depend on different processes and with the hypothesis that glucocorticoid
      activity contributes to the processes involved in the consolidation of some forms
      of memory.

PMID- 9013505
TI  - Bicuculline administration into basolateral amygdala facilitates trace
      conditioning of odor aversion in the rat.
AB  - This study investigated the effect of bicuculline methiodide (BMI) microinjection
      into basolateral amygdala (BLA) on conditioned odor aversion. Bilateral
      injections of BMI (39 or 59 pmol/0.2 microliter) or artificial CSF were done in
      the BLA 5 min after the presentation of the conditioned stimulus (water intake at
      an almond-scented tube). This was followed 30 min later by lithium chloride
      induced toxicosis. Whereas under these experimental conditions control rats (CSF
      injected) did not develop a conditioned odor aversion, BMI-treated rats (59 pmol)
      did so, suggesting that the blockade of GABAA receptors facilitated this
      learning. This facilitation was unlikely due to an unconditioned action of BMI,
      as a group microinjected with 59 pmol of BMI but not intoxicated did not display
      conditioned aversion. This result suggest that blockade of the GABAA receptors
      can prolong the olfactory trace duration, making it accessible to association
      with delayed toxicosis. Combined with previous results, these data support the
      hypothesis that the GABAergic system of the basolateral amygdala exerts control
      over the duration of a short-term odor trace in our conditioned odor aversion
      paradigms.

PMID- 9013519
TI  - Laparoscopic ultrasonography for abdominal tumor staging: technical aspects and
      imaging findings.
AB  - Since 1992 diagnostic laparoscopy combined with laparoscopic ultrasonography has
      been performed in our center in more than 300 patients for staging of tumors of
      the liver, bile ducts, pancreas, esophagus, and gastric cardia. In this article
      our experience with laparoscopic ultrasonography for abdominal tumor staging is
      described, with particular attention for the technical aspects, imaging findings,
      limitations, and pitfalls.

PMID- 9013520
TI  - CT prediction of irresectability in esophageal carcinoma: value of additional
      patient positions and relation to patient outcome.
AB  - BACKGROUND: To improve computed tomographic (CT) prediction of local
      irresectability and to correlate preoperative CT findings with patient outcome.
      METHODS: Eighty-five patients with esophageal carcinoma underwent CT in supine,
      left lateral decubitus, and prone positions. CT signs that were indicative of
      local irresectability included (1) an angle of contact >45 degrees with the
      aorta; (2) obliteration of triangular fat pad between the tumor, aorta, and
      spine; (3) tumor contiguous with the aorta in all three positions; and (4)
      indentation of the airway in all three positions. RESULTS: All CT signs
      indicative for local irresectability concerning the aorta had comparable
      percentages of false-positive scans (75%) when correlated with surgical findings.
      When correlated with pathologic findings, >45 degrees angle of contact with the
      aorta yielded the fewest false-positive cases (9%). Concerning the airway,
      additional positions changed the staging correctly in 1 of 18 cases. Median
      survival was 21 and 8 months, respectively, for tumors considered CT resectable
      or irresectable. CONCLUSION: Additional patient positions do not improve the CT
      prediction of aortic invasion. Predicted resectability correlates with a
      significant longer life expectancy.

PMID- 9013521
TI  - Esophageal carcinoma.

PMID- 9013522
TI  - Spiral CT angiography of the abdomen.

PMID- 9013524
TI  - Abdominal metastases of infiltrating lobular breast carcinoma: CT and
      fluoroscopic imaging findings.
AB  - Infiltrating lobular carcinoma accounts for only a small fraction of breast
      carcinomas, with most patients having infiltrating ductal carcinoma. The
      metastatic patterns of ductal and lobular carcinoma have been shown to be
      markedly different. Infiltrating lobular carcinoma metastasizes significantly
      more often to the gastrointestinal tract, pelvic organs,
      peritoneum/retroperitoneum, and urinary tract than does infiltrating ductal
      carcinoma. This point has significance for follow-up, the diagnosis of abdominal
      symptoms, and the therapeutic options for these patients. This article
      illustrates the broad spectrum of abdominal metastases from lobular breast
      carcinoma that may be detected with computed tomographic and fluoroscopic
      examinations, and it describes the role of imaging in the diagnosis of metastatic
      disease in these patients.

PMID- 9013523
TI  - Duodenal schwannoma causing gastrointestinal bleeding: helical CT findings.
AB  - Neurogenic tumors of the small intestine are extremely rare and represent an
      unusual cause of gastrointestinal hemorrhage. We present a case of schwannoma of
      the fourth portion of the duodenum demonstrated by helical computed tomography.
      Multiplanar reconstructions showed a hypervascular tumor arising from the
      inferior wall of the duodenum. The use of water as oral contrast agent instead of
      iodinated contrast permitted a better visualization of the intact mucosa and
      differentiated a hypervascular tumor from hypodense gastrointestinal content.

PMID- 9013525
TI  - Crohn disease: CT findings after treatment.
AB  - Within a period of 5 years, we followed by computed tomography (CT) three
      patients with Crohn disease who were undergoing treatment. From the spectrum of
      disease abnormalities, some subsided and others remained. Bowel wall thickening
      was the most common pretreatment CT finding but was somewhat altered after
      treatment.

PMID- 9013526
TI  - Magnetic resonance imaging of Crohn disease: early recognition of treatment
      response and relapse.
AB  - A patient with active Crohn disease was evaluated by MRI at admission, clinical
      remission, and a new relapse. The MRI-estimated disease extension correlated with
      surgical findings, whereas ultrasonography underestimated and a small bowel
      series overestimated the extension. MRI disclosed the disappearance of intestinal
      edema at the time of clinical remission and, in contrast to ultrasonography,
      showed an abscess and a fistula, confirmed by surgery, at the new relapse.

PMID- 9013527
TI  - Sonographic assessment of the normal and abnormal bowel wall in nondiverticular
      ileitis and colitis.
AB  - BACKGROUND: To assess the value of high resolution sonography (HRS) in
      identifying normal and inflammatory bowel wall in nondiverticular ileitis and
      colitis by using a segment-by-segment analysis. METHODS: Thirty-five HRS were
      performed in patients with nondiverticular inflammatory bowel disease, without
      knowledge of clinical, endoscopic, and radiologic data. HRS evaluated separately
      five intestinal segments (terminal ileum, cecum/ascending colon, transverse,
      descending colon, and sigmoid colon) and was considered positive for inflammation
      when wall thickness during compression exceeded 3 mm. We compared HRS findings
      with results of endoscopy or enteroclysis performed within 8 days of HRS;
      endoscopic and radiologic results were classified into two subgroups: mild
      inflammatory lesions and frank inflammatory lesions. RESULTS: Segment-by-segment
      analysis resulted in an accuracy of 81%, a sensitivity of 70%, and a specificity
      of 93%. Sensitivity was significantly lower for mild lesions (52%) than for frank
      lesions (87%, p < .001). Of the 32 patients having an inflammatory bowel
      condition, 29 (91%) had at least one segment correctly identified as inflammatory
      by HRS. CONCLUSION: Even if relatively insensitive for minor lesions, HRS is a
      promising, minimally invasive method for assessing normal and inflammatory bowel
      wall in nondiverticular ileitis and colitis.

PMID- 9013528
TI  - Imaging modalities in the puzzling world of inflammatory bowel disease.

PMID- 9013529
TI  - Pelvic silicone prosthesis for prevention of radiation enteritis: US and CT
      features.
AB  - A patient with a pelvic silicone prosthesis is presented. The sonographic and
      computed tomographic features in such patients can be confusing and incorrectly
      interpreted unless the radiologist knows that the prosthesis had been inserted as
      a radioprotective device.

PMID- 9013530
TI  - Hepatic focal nodular hyperplasia: findings on color Doppler ultrasound.
AB  - BACKGROUND: We assessed the color Doppler ultrasound (US) findings in focal
      nodular hyperplasia (FNH). METHODS: Seven FNH lesions were imaged with color
      Doppler US and hepatic angiography. RESULTS: In four lesions, color Doppler
      demonstrated a central stellate vascular appearance which correlated with central
      feeding artery with spoke-wheel sign angiographically. Except for one lesion,
      color Doppler US imaging correlated with angiographic findings. CONCLUSIONS:
      Color Doppler US is capable of demonstrating the typical findings of a central
      feeding artery and stellate vascular pattern in many cases of FNH.

PMID- 9013531
TI  - High-resolution MR imaging evaluation of hepatocellular carcinoma.
AB  - PURPOSE: To determine the utility of high-resolution MR imaging for
      hepatocellular carcinoma. MATERIALS AND METHODS: High-resolution MR images with a
      512 matrix in a right to left frequency encoding direction were obtained in 20
      consecutive patients with known or suspected hepatocellular carcinoma (HCC). Six
      series of breath-hold images of the entire liver [T1- and T2-weighted fast spin
      echo sequences, T1-weighted fast low-angle shot gradient echo sequence and three
      phased contrast-enhanced dynamic study using the latter) were obtained using a
      phased-array multicoil. RESULTS: HCC was depicted in 15 patients on the MR
      images, and the diagnosis was confirmed at pathology in 13 and at imaging in the
      other two. In the remaining five patients, HCC was correctly ruled out with MR
      imaging. CONCLUSION: High-resolution MR imaging is a promising method in the
      evaluation of HCC.

PMID- 9013532
TI  - Carcinoma of the gallbladder: color Doppler ultrasound and CT findings.
AB  - A case of a large polypoidal gallbladder carcinoma presenting with empyema is
      described. Heterogeneous echoes filled the gallbladder lumen on gray-scale
      sonography. Color Doppler ultrasound detected vascularity within the gallbladder
      lumen, thereby differentiating the intraluminal tumor from isoechoic sludge and
      pus. Correlative computed tomography showed an enhancing intraluminal mass, with
      small enhancing vessels that corresponded to those seen with color Doppler
      sonography.

PMID- 9013533
TI  - Choledochal cyst with adenocarcinoma in the cystically dilated intrahepatic bile
      duct.
AB  - A rare case of choledochal cyst complicated by papillary adenocarcinoma in the
      cystically dilated intrahepatic bile duct is reported. The tumor was located in
      the neck of the cystic lesion, and imaging modalities failed to show
      communication between the cystic lesion and the bile ducts.

PMID- 9013534
TI  - Primary sclerosing cholangitis.

PMID- 9013535
TI  - Detection of pancreatic adenocarcinoma: relative value of arterial and late
      phases of spiral CT.
AB  - BACKGROUND: Spiral computed tomography (CT) allows the pancreas to be imaged
      during peak contrast levels owing to the capability of fast data acquisition. The
      objective of this study was to evaluate the relative value of the arterial and
      late phases of spiral CT for detecting pancreatic adenocarcinomas. METHODS:
      Twenty-two patients with pathologically proved pancreatic adenocarcinomas
      underwent two-phase spiral CT. The CT scans were performed with 5 mm collimation
      and 5 mm/s table speed. Images during the arterial and late phases were obtained
      at 30- and 180-second delays, respectively. The images of the arterial phase were
      compared with those of the late phase in terms of tumor conspicuity from
      surrounding pancreatic parenchyma and tumor detectability by means of a 3-point
      grading system: 1 (poor), 2 (fair), and 3 (good). RESULTS: In terms of tumor
      conspicuity from surrounding pancreatic parenchyma, 16 lesions (73%) were good, 5
      lesions (23%) were fair, and 1 lesion (4%) was poor during the arterial phase,
      whereas 6 lesions (27%) were good, 9 lesions (41%) were fair, and 7 lesions (32%)
      were poor during the late phase (p = 0.0007). The arterial phase was superior to
      the late phase in 16 patients (73%) and equal in 6 patients (27%). For tumor
      detectability, 18 lesions (82%) were good, 3 lesions (14%) were fair, and 1
      lesion (4%) was poor during the arterial phase, whereas 10 lesions (45%) were
      good, 7 lesions (32%) were fair, and 5 lesions (23%) were poor during the late
      phase (p = 0.0033). For detectability, the arterial phase was superior to the
      late phase in 14 patients (64%) and equal in 8 patients (36%). CONCLUSION: The
      arterial phase of spiral CT is superior to the late phase, which is equivalent to
      conventional CT for detecting pancreatic adenocarcinoma.

PMID- 9013536
TI  - Helical CT evaluation of arterial invasion in pancreatic tumors: comparison with
      angiography.
AB  - BACKGROUND: Although helical computed tomography (HCT) has been widely employed
      for the evaluation of pancreatic tumors, its capability in the diagnosis of
      peripancreatic arterial invasion has not been established. METHODS: HCT with a
      sequential cine-display was carried out in 34 patients with solid pancreatic
      tumors and 28 control subjects without angiographic abnormality. The HCT scans
      were compared with angiograms. RESULTS: All major arteries (celiac, superior
      mesenteric, splenic, gastroduodenal) and superoanterior pancreaticoduodenal
      arteries were well demonstrated by HCT in control subjects. However, posterior
      pancreaticoduodenal arcades and other smaller arteries were poorly identified.
      Although 19 major arterial invasions were equally diagnosed by HCT and
      angiography in patients with pancreatic tumors, only 4 of 11 minor arterial
      invasions were correctly diagnosed by HCT. CONCLUSIONS: Although HCT has some
      limitations in the evaluation of minor peripancreatic arteries, it can provide
      enough information for making a decision about conducting pancreatic surgery.

PMID- 9013537
TI  - Cervical carcinoma: role of imaging.

PMID- 9013539
TI  - Anastomoses between the spermatic and visceral veins: a retrospective study of
      500 consecutive patients.
AB  - BACKGROUND: Do visceral-spermatic vein shunts have any clinical impact on
      sclerotherapy of varicoceles? METHODS: The spermatic venograms of 500 consecutive
      patients were retrospectively reviewed to classify visceral-spermatic
      communications. Men with an average age of 27.8 years (range 11-65 years old)
      underwent sclerotherapy of a varicocele. Of the 500 men, 445 were referred for
      oligoasthenospermia (89%), 45 for pain (9%), and 10 for prevention of infertility
      (2%). After bilateral catheterization, percutaneous sclerosis was performed below
      the upper third of the sacroiliac joint. RESULTS: Three hundred forty patients
      (68%) had left-sided, 10 (2%) had right-sided, and 150 (30%) had bilateral
      varicoceles. Left side: Of 46 (9.4%) anastomoses, one (0.2%) communicated with
      the splenic vein and 45 (9.2%) with the inferior mesenteric vein of which 25
      (5.1%) were a colic trunk with a competent valve, 15 (3.1%) were venules, and
      five (1%) were a single or double anastomosis. Right side: Of 48 (29.6%)
      anastomoses to the superior mesenteric vein, 34 (21%) were venules, 12 (7.4%)
      were a colic trunk with a competent valve, and two (1.2%) were a single or double
      vein. Our varicocele recurrence rate was only 1.2%. CONCLUSION: Visceral
      spermatic vein communications are classified by number, morphology, and site.
      Percutaneous sclerotherapy could be optimized when performed caudally to these
      communications.

PMID- 9013538
TI  - MR imaging evaluation of renal cell carcinoma.
AB  - BACKGROUND: This study examines the minimally required imaging protocol needed
      for detection and staging of renal cell carcinoma (RCC). METHODS: In 81 patients
      (21 women, 60 men; mean age = 62 years) with 85 RCCs, T1-weighted (T1WI),
      contrast-enhanced T1-weighted (Gd-T1WI), T2-weighted (T2WI), and gradient
      recalled echo-fast low flip angle shot (GRE/FLASH) images were evaluated alone
      and in combination. Surgical-pathological findings were available in all patients
      and were considered the standard of reference. RESULTS: Tumor detection for
      lesions smaller than 3 cm was better on Gd-T1WI than on any other sequence, but
      only the comparison with noncontrast T1WI and GRE/FLASH was statistically
      significant (detection: T1WI = 33%, Gd-TIWI = 80%, T2WI = 60%, GRE = 47%). The
      respective accuracies of T1WI, Gd-T1WI, T2WI, and GRE/FLASH images were 81%, 78%,
      71%, and 62% for evaluating local tumor extension; 90%, 88%, 89%, and 85% for
      lymphadenopathy; and 89%, 81%, 91%, and 95% for renal vein thrombus. The
      combination of T1WI and GRE sequences rendered the highest overall staging
      accuracy. CONCLUSION: For tumor detection, contrast-enhanced T1WI is necessary
      for lesions smaller than 3 cm. For tumor staging, although the addition of GRE
      results in significant improvement in the evaluation of venous thrombus, any
      combination of two sequences will result in similar accuracy, and the use of
      multiple sequences is not necessary.

PMID- 9013540
TI  - Gadoteridol as an alternative contrast agent for retrograde pyelography.

PMID- 9013541
TI  - Peritoneal carcinomatosis.

PMID- 9013542
TI  - A role for Sam68 in cell cycle progression antagonized by a spliced variant
      within the KH domain.
AB  - Sam68 is the main tyrosine-phosphorylated and Src-associated protein in mitotic
      cells. Sam68 exhibits a conserved functional KH (hnRNPK homology) RNA binding
      domain and binds single strand nucleic acids. Tyrosine phosphorylation mediates
      the interaction of Sam68 with many SH3- and SH2-containing proteins and
      negatively regulates its nucleic acid binding properties. But the function and
      the impact of Sam68 on cell signaling and cell proliferation remains elusive. We
      report here the identification of a natural isoform of Sam68 with a deletion
      within the KH domain. This isoform, called Sam68DeltaKH, is specifically
      expressed at growth arrest upon confluency in normal cells. In cells that do not
      enter quiescence at confluency such as Src-transformed cells, no recruitment of
      Sam68DeltaKH is observed. Transfected Sam68DeltaKH inhibits serum-induced DNA
      synthesis and cyclin D1 expression. Sam68 overcomes these effects, suggesting
      that isoforms of Sam68 are involved, through KH domain signaling, in cell
      proliferation, and more precisely in G1/S transition.

PMID- 9013543
TI  - Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet
      microsomes.
AB  - Cyclic ADP-ribose (cADPR) is a second messenger for Ca2+ mobilization via the
      ryanodine receptor (RyR) from islet microsomes for insulin secretion (Takasawa,
      S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In the
      present study, FK506, an immunosuppressant that prolongs allograft survival, as
      well as cADPR were found to induce the release of Ca2+ from islet microsomes.
      After islet microsomes were treated with FK506, the Ca2+ release by cADPR from
      microsomes was reduced. cADPR as well as FK506 bound to FK506-binding protein
      12.6 (FKBP12.6), which we also found occurs naturally in islet microsomes. When
      islet microsomes were treated with cADPR, FKBP12.6 dissociated from the
      microsomes and moved to the supernatant, releasing Ca2+ from the intracellular
      stores. The microsomes that were then devoid of FKBP12.6 did not show Ca2+
      release by cADPR. These results strongly suggest that cADPR may be the ligand for
      FKBP12.6 in islet RyR and that the binding of cADPR to FKBP12.6 frees the RyR
      from FKBP12.6, causing it to release Ca2+.

PMID- 9013544
TI  - Activation of the nuclear receptor LXR by oxysterols defines a new hormone
      response pathway.
AB  - Accumulation of cholesterol causes both repression of genes controlling
      cholesterol biosynthesis and cellular uptake and induction of cholesterol 7alpha
      hydroxylase, which leads to the removal of cholesterol by increased metabolism to
      bile acids. Here, we report that LXRalpha and LXRbeta, two orphan members of the
      nuclear receptor superfamily, are activated by 24(S), 25-epoxycholesterol and
      24(S)-hydroxycholesterol at physiologic concentrations. In addition, we have
      identified an LXR response element in the promoter region of the rat cholesterol
      7alpha-hydroxylase gene. Our data provide evidence for a new hormonal signaling
      pathway that activates transcription in response to oxysterols and suggest that
      LXRs play a critical role in the regulation of cholesterol homeostasis.

PMID- 9013545
TI  - Identification of previously unrecognized common elements in eukaryotic
      promoters. A ribosomal RNA gene initiator element for RNA polymerase I.
AB  - A new ribosomal RNA promoter element with a functional role similar to the RNA
      polymerase II initiator (Inr) was identified. This sequence, which we dub the
      ribosomal Inr (rInr) is unusually conserved, even in normally divergent RNA
      polymerase I promoters. It functions in the recruitment of the fundamental, TATA
      binding protein (TBP)-containing transcription factor, TIF-IB. All upstream
      elements of the exceptionally strong Acanthamoeba castellanii ribosomal RNA core
      promoter, to within 6 base pairs of the transcription initiation site (tis), can
      be deleted without loss of specific transcription initiation. Thus, the A.
      castellanii promoter can function in a manner similar to RNA polymerase II TATA
      less promoters. Sequence-specific photo-cross-linking localizes a 96-kDa subunit
      of TIF-IB and the second largest RNA polymerase I subunit (A133) to the rInr
      sequence. A185 also photo-cross-links when polymerase is stalled at +7.

PMID- 9013546
TI  - MyoD functions as a transcriptional repressor in proliferating myoblasts.
AB  - The myogenic basic helix-loop-helix (myo-bHLH) proteins are a family of
      transcriptional regulators expressed in myoblasts and differentiated skeletal
      muscle. Ectopic expression of myo-bHLH regulators transdetermines some fibroblast
      cell lines into myoblasts, which exit the cell cycle and differentiate into
      skeletal muscle when cultured in low mitogen medium. While members of the myo
      bHLH family have been shown to function as transcriptional activators in
      differentiating muscle, the molecular basis of their function in proliferating
      myoblasts has not been elucidated. In this report, we present evidence that MyoD
      functions as a transcriptional repressor in myoblasts. We show that transcription
      from a cyclin B1 promoter construct is repressed in proliferating myoblasts and
      that repression is mediated by a pair of MyoD binding sites. We also show that
      transcription from the cyclin B1 promoter is repressed in proliferating C3H10T1/2
      cells by ectopic expression of MyoD. These results demonstrate that MyoD can
      repress transcription of specific genes in proliferating cells, a novel function
      that may be important to maintenance of the myogenic phenotype and to cell cycle
      regulation in myoblasts.

PMID- 9013547
TI  - Differential mechanisms of cytochrome P450 inhibition and activation by alpha
      naphthoflavone.
AB  - The anticarcinogenicity of some flavonoids has been attributed to modulation of
      the cytochrome P450 enzymes, which metabolize procarcinogens to their activated
      forms. However, the mechanism by which flavonoids inhibit some P450-mediated
      activities while activating others is a longstanding, intriguing question. We
      employed flash photolysis to measure carbon monoxide binding to P450 as a rapid
      kinetic technique to probe the interaction of the prototype flavonoid alpha
      naphthoflavone with human cytochrome P450s 1A1 and 3A4, whose benzo[a]pyrene
      hydroxylation activities are respectively inhibited and stimulated by this
      compound. This flavonoid inhibited P450 1A1 binding to benzo[a]pyrene via a
      classical competitive mechanism. In contrast, alpha-naphthoflavone stimulated
      P450 3A4 by selectively binding and activating an otherwise inactive
      subpopulation of this P450 and promoting benzo[a]pyrene binding to the latter.
      These data indicate that flavonoids enhance activity by increasing the pool of
      active P450 molecules within this P450 macrosystem. Activators in other
      biological systems may similarly exert their effect by expanding the population
      of active receptor molecules.

PMID- 9013548
TI  - Unveiling the substrate specificity of meprin beta on the basis of the site in
      protein kinase A cleaved by the kinase splitting membranal proteinase.
AB  - The kinase splitting membranal proteinase (KSMP) is a metalloendopeptidase that
      inactivates the catalytic (C) subunit of protein kinase A (PKA) by clipping off
      its carboxyl terminal tail. Here we show that this cleavage occurs at Glu332
      Glu333, within the cluster of acidic amino acids (Asp328-Glu334) of the kinase.
      The Km values of KSMP and of meprin beta (which reproduces KSMP activity) for the
      C-subunit are below 1 microM. The Km for peptides containing a stretch of four
      Glu residues are in the micromolar range, illustrating the significant
      contribution of this cluster to the substrate recognition of meprin beta. This
      conclusion is supported by a systematic study using a series of the C-subunit
      mutants with deletions and mutations in the cluster of acidics. Hydrophobic amino
      acids vicinal to the cleavage site increase the Kcat of the proteinase. These
      studies unveil a new specificity for meprin beta, suggesting new substrates that
      are 1-2 orders of magnitude better in their Km and Kcat than those commonly used
      for meprin assay. A search for substrates having such a cluster of acidics and
      hydrophobics, which are accessible to meprin under physiological conditions,
      point at gastrin as a potential target. Indeed, meprin beta is shown to cleave
      gastrin at its cluster of five glutamic acid residues and also at the M-D bond
      within its WMDF-NH2 sequence, which is indispensable for all the known biological
      activities of gastrins. The latter meprin cleavage will lead to the inactivation
      of gastrin and thus to the control of its activity.

PMID- 9013549
TI  - Identification of Glu-330 as the catalytic nucleophile of Candida albicans exo
      beta-(1,3)-glucanase.
AB  - The exo-beta-(1,3)-glucanase from Candida albicans hydrolyzes cell wall beta
      glucans via a double-displacement mechanism involving a glycosyl enzyme
      intermediate. Reaction of the enzyme with 2',4'-dinitrophenyl-2-deoxy-2-fluoro
      beta-D-glucopyranoside resulted in the time-dependent inactivation of this enzyme
      via the accumulation of a 2-deoxy-2-fluoro-glycosyl-enzyme intermediate as
      monitored also by electrospray mass spectrometry. The catalytic competence of
      this intermediate is demonstrated by its reactivation through hydrolysis (kreact
      = 0.0019 min-1) and by transglycosylation to benzyl thio-beta-D-glucopyranoside
      (kreact = 0.024 min-1; Kreact = 56 mM). Peptic digestion of the labeled enzyme
      followed by tandem mass spectrometric analysis in the neutral loss mode allowed
      detection of two glycosylated active site peptides, the sequences of which were
      identified as NVAGEW and NVAGEWSAA. A crucial role for Glu-330 is confirmed by
      site-directed mutagenesis at this site and kinetic analysis of the resultant
      mutant. The activity of the Glu-330 --> Gln mutant is reduced over 50,000-fold
      compared to the wild type enzyme. The glutamic acid, identified in the
      exoglucanase as Glu-330, is completely conserved in this family of enzymes and is
      hereby identified as the catalytic nucleophile.

PMID- 9013550
TI  - Human mucin gene MUC5B, the 10.7-kb large central exon encodes various alternate
      subdomains resulting in a super-repeat. Structural evidence for a 11p15.5 gene
      family.
AB  - Human mucin gene MUC5B is mapped clustered with MUC6, MUC2, and MUC5AC on
      chromosome 11p15.5. We report here the isolation of three overlapping genomic
      clones of human MUC5B spanning approximately 40 kilobases. We have determined
      their partial restriction maps and the intron-exon boundaries of the central
      region encoding a single open reading frame. This coding region has been
      completely sequenced. Its length is 10,713 base pairs, and it encodes a 3570
      amino acid peptide. Nineteen subdomains have been individualized. Some subdomains
      show similarity to each other, creating larger composite repeat units that we
      have called super-repeats. Four super-repeats of 528 amino acid residues are thus
      observed within the central exon. Each comprises (i) a subdomain composed of 11
      repeats of the irregular repeat of 29 amino acid residues, (ii) a unique
      conserved subdomain with no typical repeat, and (iii) a cysteine-rich subdomain.
      This latter subdomain has high sequence similarity to the cysteine-rich domains
      described in MUC2 and MUC5AC. Sequence data of these three genes, together with
      their clustered organization, lead us to suggest that they may be a part of a
      multigene family. The super-repeat present in MUC5B is the largest ever
      determined in mucin genes and the central exon of this gene is, by far, the
      largest reported for a vertebrate gene.

PMID- 9013551
TI  - Dimerization regulates the enzymatic activity of Escherichia coli outer membrane
      phospholipase A.
AB  - The outer membrane phospholipase A (OMPLA) of Escherichia coli is present in a
      dormant state in the cell envelope. The enzyme is activated by various processes,
      which have in common that they perturb the outer membrane. Kinetic experiments,
      chemical cross-linking, and analytical ultracentrifugation were carried out with
      purified, detergent-solubilized OMPLA to understand the underlying mechanism that
      results in activation. Under conditions in which the enzyme displayed full
      activity, OMPLA was dimeric. High detergent concentrations or very dilute protein
      concentrations resulted in low specific activity of the enzyme, and under those
      conditions the enzyme was monomeric. The cofactor Ca2+ was required for
      dimerization. Covalent modification of the active site serine with
      hexadecylsulfonylfluoride resulted in stabilization of the dimeric form and a
      loss of the absolute calcium requirement for dimerization. The results of these
      experiments provide evidence for dimerization as the molecular mechanism by which
      the enzymatic activity of OMPLA is regulated. This dimerization probably plays a
      role in vivo as well. Data from chemical cross-linking on whole cells indicate
      that OMPLA is present in the outer membrane as a monomer and that activation of
      the enzyme induces dimerization concurrent with the appearance of enzymatic
      activity.

PMID- 9013552
TI  - DNA binding by the male and female doublesex proteins of Drosophila melanogaster.
AB  - Drosophila yolk protein genes are regulated by doublesex male protein (DSXM) in
      males and doublesex female protein (DSXF) in females. Both proteins bind to the
      same DNA sites from which DSXM represses and DSXF activates transcription. The
      proteins are identical through 397 NH2-terminal amino acids that include domains
      for oligomerization and DNA binding. The remaining COOH termini are sex-specific
      and include an essential part of a second oligomerization domain. We report here
      mobility shift assays that examine the DNA binding properties of purified DSXM
      and DSXF. Dimers of DSXM and DSXF bind to a regulatory site, dsxA, with the same
      affinity (Kapp = 0.2 nM), specificity (specific/nonspecific approximately 1.2 x
      10(4)), and dependence on monovalent and divalent cations. The DNA association
      rate constants also are indistinguishable (kon = 4.6 x 10(6) M-1 s-1) as are the
      several terms of the dissociation reaction. Dissociation has an intrinsic rate of
      koff = 5.1 x 10(-4) s-1 and other rate terms that depend on the free
      concentration of specific DNA binding sites (2.4 x 10(4) M-1 s-1) or nonspecific
      binding sites (2.4 M-1 s-1). This first order dependence on unbound DNA suggests
      that a direct transfer between DNAs is likely to occur when DSX proteins search
      for specific sites in the many short open DNA regions of chromatin. Overall,
      dimer binding to individual DNA sites appears to be determined by the sex
      nonspecific part of the two proteins. We infer that the sex-specific
      oligomerization domains play roles in binding cooperativity to multiple DNA sites
      or in other protein:protein interactions.

PMID- 9013553
TI  - Glycine residues provide flexibility for enzyme active sites.
AB  - The high resolution refined structures of 23 enzymes were analyzed to determine
      the properties of amino acids involved in active site regions. These regions were
      found to be rich in G-X-Y or Y-X-G oligopeptides, where X and Y are polar and non
      polar residues, respectively, that are small and with low polarity. Other regions
      of the enzyme molecules have significantly fewer of these sequences. These
      features suggest that glycine residues may provide flexibility necessary for
      enzyme active sites to change conformation, and the G-X-Y or Y-X-G oligopeptides
      may be a motif for the formation of enzyme active sites.

PMID- 9013554
TI  - Tyrosine phosphorylation of annexin II tetramer is stimulated by membrane
      binding.
AB  - In the present article we have examined if the interaction of the Ca2+-binding
      protein, annexin II tetramer (AIIt) with the plasma membrane phospholipids or
      with the submembranous cytoskeleton, effects the accessibility of the tyrosine
      phosphorylation site of AIIt. In the presence of Ca2+, pp60(c-src) catalyzed the
      incorporation of 0.22 +/- 0.05 mol of phosphate/mol of AIIt (mean +/- S.D., n =
      5). The Ca2+-dependent binding of AIIt to purified adrenal medulla plasma
      membrane or phosphatidylserine vesicles stimulated the pp60(c-src)-dependent
      phosphorylation of AIIt to 0.62 +/- 0.04 mol of phosphate/mol of AIIt (mean +/-
      S.D., n = 5) or 0.93 +/- 0.07 mol of phosphate/mol of AIIt (mean +/- S.D., n =
      5), respectively. Phosphatidylserine- or phosphatidylinositol-containing vesicles
      but not vesicles composed of phosphatidylcholine or phosphatidylethanolamine,
      stimulated the phosphorylation of AIIt. In contrast, the binding of AIIt to F
      actin resulted in the incorporation of only 0.04 +/- 0.04 mol of phosphate/mol of
      AIIt (mean +/- S.D., n = 5). These results suggest that the interaction of AIIt
      with plasma membrane and not the submembranous cytoskeleton, activates the
      tyrosine phosphorylation of AIIt by inducing a conformational change in the
      protein resulting in the enhanced exposure or accessibility of the tyrosine
      phosphorylation site.

PMID- 9013555
TI  - Mouse mastocytoma cells synthesize undersulfated heparin and chondroitin sulfate
      in the presence of brefeldin A.
AB  - In order to study the subcellular localization and organization of the enzymes
      involved in the glycosylation of the hybrid proteoglycan serglycin, mouse
      mastocytoma cells were metabolically labeled with [35S]sulfate or [3H]glucosamine
      in the absence or presence of brefeldin A. This drug is known to induce a
      disassembly of the proximal part of the Golgi complex, resulting in a
      redistribution of cis-, medial-, and trans-Golgi resident enzymes back to the
      endoplasmic reticulum, and to block the anterograde transport of proteins to the
      trans-Golgi network. Although the total incorporation of [3H]glucosamine into
      glycosaminoglycan chains was reduced to about 25% in brefeldin A-treated cells
      compared to control cells, both control cells and cells treated with brefeldin A
      synthesized heparin as well as chondroitin sulfate chains. Therefore, enzymes
      involved in the biosynthesis of both types of glycosaminoglycan chains seem to be
      present proximal to the trans-Golgi network in these cells. Chondroitin sulfate
      and heparin synthesized in cells exposed to brefeldin A were undersulfated, as
      demonstrated by ion-exchange chromatography, compositional analyses of
      disaccharides, as well as by a lower [35S]sulfate/[3H]glucosamine ratio compared
      to controls. In heparin biosynthesis, both N- and O-sulfation reactions were
      impaired, with a larger relative decrease in 2-O-sulfation than in 6-O-sulfation.
      Despite undersulfation, the heparin chains synthesized in the presence of
      brefeldin A were larger (30 kDa) than the heparin synthesized by control cells
      (20 kDa). The reduced [3H]glucosamine incorporation in brefeldin A-treated cells
      was partly due to decreased number of glycosaminoglycan chains synthesized, but
      also to the biosynthesis of chondroitin sulfate chains of smaller molecular size
      (8 versus 15 kDa in control cells). Brefeldin A had no effect on the
      glycosaminoglycan synthesis when used in a cell-free, microsomal fraction,
      indicating that brefeldin A does not interfere directly with the enzymes involved
      in the biosynthesis of glycosaminoglycans.

PMID- 9013556
TI  - Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of
      the kinetics of the glycolytic enzymes.
AB  - In trypanosomes the first part of glycolysis takes place in specialized
      microbodies, the glycosomes. Most glycolytic enzymes of Trypanosoma brucei have
      been purified and characterized kinetically. In this paper a mathematical model
      of glycolysis in the bloodstream form of this organism is developed on the basis
      of all available kinetic data. The fluxes and the cytosolic metabolite
      concentrations as predicted by the model were in accordance with available data
      as measured in non-growing trypanosomes, both under aerobic and under anaerobic
      conditions. The model also reproduced the inhibition of anaerobic glycolysis by
      glycerol, although the amount of glycerol needed to inhibit glycolysis completely
      was lower than experimentally determined. At low extracellular glucose
      concentrations the intracellular glucose concentration remained very low, and
      only at 5 mM of extracellular glucose, free glucose started to accumulate
      intracellularly, in close agreement with experimental observations. This biphasic
      relation could be related to the large difference between the affinities of the
      glucose transporter and hexokinase for intracellular glucose. The calculated
      intraglycosomal metabolite concentrations demonstrated that enzymes that have
      been shown to be near-equilibrium in the cytosol must work far from equilibrium
      in the glycosome in order to maintain the high glycolytic flux in the latter.

PMID- 9013557
TI  - Dexamethasone induces posttranslational degradation of GLUT2 and inhibition of
      insulin secretion in isolated pancreatic beta cells. Comparison with the effects
      of fatty acids.
AB  - GLUT2 expression is strongly decreased in glucose-unresponsive pancreatic beta
      cells of diabetic rodents. This decreased expression is due to circulating
      factors distinct from insulin or glucose. Here we evaluated the effect of
      palmitic acid and the synthetic glucocorticoid dexamethasone on GLUT2 expression
      by in vitro cultured rat pancreatic islets. Palmitic acid induced a 40% decrease
      in GLUT2 mRNA levels with, however, no consistent effect on protein expression.
      Dexamethasone, in contrast, had no effect on GLUT2 mRNA, but decreased GLUT2
      protein by about 65%. The effect of dexamethasone was more pronounced at high
      glucose concentrations and was inhibited by the glucocorticoid antagonist RU-486.
      Biosynthetic labeling experiments revealed that GLUT2 translation rate was only
      minimally affected by dexamethasone, but that its half-life was decreased by 50%,
      indicating that glucocorticoids activated a posttranslational degradation
      mechanism. This degradation mechanism was not affecting all membrane proteins,
      since the alpha subunit of the Na+/K+-ATPase was unaffected. Glucose-induced
      insulin secretion was strongly decreased by treatment with palmitic acid and/or
      dexamethasone. The insulin content was decreased ( approximately 55 percent) in
      the presence of palmitic acid, but increased ( approximately 180%) in the
      presence of dexamethasone. We conclude that a combination of elevated fatty acids
      and glucocorticoids can induce two common features observed in diabetic beta
      cells, decreased GLUT2 expression, and loss of glucose-induced insulin secretion.

PMID- 9013558
TI  - Expression of a constitutively active Ca2+/calmodulin-dependent kinase in
      Aspergillus nidulans spores prevents germination and entry into the cell cycle.
AB  - The unique gene for Ca2+/calmodulin-dependent protein kinase (CaMK) has been
      shown to be essential in Aspergillus nidulans. Disruption of the gene prevents
      entry of spores into the nuclear division cycle. Here we show that expression of
      a constitutively active form of CaMK also prevents spores from entering the first
      S phase in response to a germinating stimulus. Expression of the constitutively
      active kinase induces premature activation of NIMEcyclin B/NIMXcdc2 in G0/G1. As
      NIMXcdc2 is present in spores, the elevation of maturation promotion factor
      activity may be secondary to the early production of NIMEcyclin B or post
      translation modification of maturation promotion factor. The expression of the
      constitutively active CaMK also results in the appearance of NIMA kinase activity
      within 1 h of the germinating signal. These results support the contention that
      the activities of maturation promotion factor and NIMA are coincidentally
      regulated in A. nidulans and suggest that the unscheduled appearance of one or
      both of these activities may be sufficient to prevent A. nidulans spores from
      entering into DNA synthesis.

PMID- 9013559
TI  - Prostaglandin synthase-1 and prostaglandin synthase-2 are coupled to distinct
      phospholipases for the generation of prostaglandin D2 in activated mast cells.
AB  - Aggregation of IgE cell surface receptors on MMC-34 cells, a murine mast cell
      line, induces the synthesis and secretion of prostaglandin D2 (PGD2). Synthesis
      and secretion of PGD2 in activated MMC-34 cells occurs in two stages, an early
      phase that is complete within 30 min after activation and a late phase that
      reaches a maximum about 6 h after activation. The early and late phases of PGD2
      generation are mediated by prostaglandin synthase 1 (PGS1) and prostaglandin
      synthase 2 (PGS2), respectively. Arachidonic acid, the substrate for both PGS1
      and PGS2, is released from membrane phospholipids by the activation of
      phospholipases. We now demonstrate that in activated mast cells (i) secretory
      phospholipase A2 (PLA2) mediates the release of arachidonic acid for early, PGS1
      dependent synthesis of PGD2; (ii) secretory PLA2 does not play a role in the
      late, PGS2-dependent synthesis of PGD2; (iii) cytoplasmic PLA2 mediates the
      release of arachidonic acid for late, PGS2-dependent synthesis of PGD2; and (iv)
      a cytoplasmic PLA2-dependent step precedes secretory PLA2 activation and is
      necessary for optimal PGD2 production by the secretory PLA2/PGS1-dependent early
      pathway.

PMID- 9013561
TI  - PG-M/versican-like proteoglycans are components of large disulfide-stabilized
      complexes in the axolotl embryo.
AB  - Large disulfide-stabilized proteoglycan complexes were previously shown to be
      synthesized by the epidermis of axolotl embryos during stages crucial to
      subepidermal migration of neural crest cells. We now show that the complexes
      contain PG-M/versican-like monomers in addition to some other component with low
      buoyant density. Metabolically 35S-labeled proteoglycans were extracted from
      epidermal explants and separated by size exclusion chromatography and density
      equilibrium gradient centrifugation. The complexes, which elute in the void
      volume on Sepharose CL-2B, were recovered at buoyant density 1.42 g/ml in CsCl
      gradients, whereas the monomer proteoglycans, which could only be liberated from
      the complexes by reduction, had a higher buoyant density (1.48 g/ml). The native
      complexes did not aggregate with hyaluronan. The purified complexes reacted with
      antibodies against a portion of a cloned PG-M/versican-like axolotl proteoglycan.
      These antibodies were found to stain the subepidermal matrix of axolotl embryos,
      suggesting that the proteoglycan complexes are encountered by neural crest cells
      during subepidermal migration. From Western blot analysis, the core protein of
      the PG-M/versican-like monomers was found to be of similar size ( approximately
      500 kDa) as those of PG-M/versican variants of other species. Another chondroitin
      sulfate proteoglycan that was present in small amounts in the epidermal extracts
      was found to be distinctly different from the similarly sized PG-M/versican-like
      monomers.

PMID- 9013562
TI  - Structure of 18 S ribosomal RNA in native 40 S ribosomal subunits.
AB  - We have analyzed the structure of 18 S rRNA in native 40 S subunits using
      chemical modification followed by primer extension. The native subunits were
      modified using the single-stranded specific reagents dimethyl sulfate and 1
      cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate. The
      modification pattern of the 18 S rRNA was compared to that obtained from derived
      40 S subunits prepared by dissociation of unprogrammed 80 S ribosomes. Eighteen
      nucleotides showed different accessibility to the chemical probes in derived and
      native subunits. Half of these nucleotides were found in the central domain of
      the rRNA between the 1060 loop and the central pseudoknot. The remaining
      nucleotides were located in two clusters in the 5'- and 3'-domains of the 18 S
      rRNA. Derived 40 S subunits are free from non-ribosomal proteins. In contrast,
      native subunits are intermediates in protein synthesis initiation and contain
      stoichiometric amounts of initiation factor 3 (Sundkvist, I. C., and Staehelin,
      T. (1975) J. Mol. Biol. 99, 401-418). The possible role of this factor in
      altering the structure of 18 S rRNA in the native 40 S subunits is discussed.

PMID- 9013560
TI  - cAMP-dependent negative regulation of rat aldehyde dehydrogenase class 3 gene
      expression.
AB  - We investigated the inhibitory effects of intracellular cyclic adenosine
      monophosphate (cAMP) levels in regulating class 3 aldehyde dehydrogenase (aldh3)
      gene expression using cultures of primary rat hepatocytes and transient
      transfection experiments with HepG2 cells. In addition to regulation by an Ah
      receptor-dependent mechanism, expression of many members of the Ah gene battery
      have been shown to be negatively regulated. As was seen for the cytochrome P450
      (cyp1A1) gene, aldh3 is transcriptionally inducible by polycyclic aromatic
      hydrocarbons (PAH), and this induction involving function of the arylhydrocarbon
      (Ah) receptor is inhibited by the protein kinase C (PKC) inhibitors, 1-(5
      isoquinolinesulfonyl)-2-methylpiperazine di-HCl (H7) and staurosporine. However,
      PAH induction of ALDH-3 activity, protein, and mRNA was potentiated 2-4-fold by
      addition of the protein kinase A (PKA) inhibitors, N-(2-(methylamino)ethyl)-5
      isoquinolinesulfonamide di-HCl (H8) and N-(2-guanidinoethyl)-5
      isoquinolinesulfonamide HCl (HA1004). These PKA inhibitors had no effect on the
      PAH induction of the cyp1A1. Protein kinase A activity of cultured hepatocytes
      was specifically inhibited by H8 and HA1004 in a concentration-dependent manner,
      but not by H7, and there was an inverse correlation observed between potentiation
      of PAH-induced aldh3 gene expression and inhibition of specific PKA activity by
      the PKA inhibitors. The cAMP analog dibutyryl cAMP, the adenylate cyclase
      activator forskolin, and the protein phosphatase 1 and 2A inhibitor okadaic acid
      all dramatically inhibited both PAH induction and H8 potentiation of PAH
      induction of aldh3 expression but had no effect on induction of cyp1A1 expression
      in cultured hepatocytes. Both basal and PAH-dependent expression of a
      chloramphenicol acetyltransferase expression plasmid containing approximately 3.5
      kilobase pairs of the 5'-flanking region of aldh3 (pALDH3.5CAT) were enhanced 3-4
      fold by the PKA inhibitor H8 but not by the PKC inhibitor H7 (>20 microM). cAMP
      analogs, activators of PKA activity, or protein phosphatase inhibitors diminished
      expression of the reporter gene in a manner identical to the native gene in
      cultured rat hepatocytes. Using deletion analysis of the pALDH3.5CAT construct,
      we demonstrated the existence of a negative regulatory region in the 5'-flanking
      region between -1057 and -991 base pairs which appears to be responsible for the
      cAMP-dependent regulation of this gene under both basal and PAH-induced
      conditions. At least two apparently independent mechanisms which involve protein
      phosphorylation regulate aldh3 expression. One involves function of the Ah
      receptor which requires PKC protein phosphorylation to positively regulate both
      aldh3 and cyp1A1 gene expression and the other a cAMP-responsive process which
      allows PKA activity to negatively regulate expression of aldh3 under either basal
      or inducible conditions.

PMID- 9013563
TI  - A novel non-heme iron-binding ferritin related to the DNA-binding proteins of the
      Dps family in Listeria innocua.
AB  - A multimeric protein that behaves functionally as an authentic ferritin has been
      isolated from the Gram-positive bacterium Listeria innocua. The purified protein
      has a molecular mass of about 240,000 Da and is composed of a single type of
      subunit (18,000 Da). L. innocua ferritin is able to oxidize and sequester about
      500 iron atoms inside the protein cage. The primary structure reveals a high
      similarity to the DNA-binding proteins designated Dps. Among the proven
      ferritins, the most similar sequences are those of mammalian L chains that appear
      to share with L. innocua ferritin the negatively charged amino acids
      corresponding to the iron nucleation site. In L. innocua ferritin, an additional
      aspartyl residue may provide a strong complexing capacity that renders the iron
      oxidation and incorporation processes extremely efficient. This study provides
      the first experimental evidence for the existence of a non-heme bacterial
      ferritin that is related to Dps proteins, a finding that lends support to the
      recent suggestion of a common evolutionary origin of these two protein families.

PMID- 9013564
TI  - Nmoc-DBHQ, a new caged molecule for modulating sarcoplasmic/endoplasmic reticulum
      Ca2+ ATPase activity with light flashes.
AB  - We report the synthesis and characterization of O[o-nitromandelyloxycarbonyl]-2,5
      di(tert-butyl)hydroquinone (Nmoc-DBHQ), a new "caged" reagent for photoreleasing
      DBHQ, a membrane-permeant, reversible inhibitor of the sarcoplasmic/endoplasmic
      reticulum Ca2+ ATPase (SERCA). The Nmoc group is a new caging group developed for
      the current application. Photolysis of Nmoc-DBHQ proceeds with t1/2 = 126 +/- 2
      micros, and t1/2 for subsequent release of DBHQ is estimated to be approximately
      5 ms. Nmoc-DBHQ thus allows rapid and reversible modulation of SERCA activity in
      living cells. Through its acetoxymethyl ester, Nmoc-DBHQ can be loaded into cells
      easily by incubation. We demonstrate the use of Nmoc-DBHQ for photomodulating
      SERCA activity in fibroblasts and vagal sensory neurons. We further demonstrate
      the utility of pulsed DBHQ photorelease for probing and manipulating dynamic
      phenomena such as [Ca2+] oscillations in fibroblasts.

PMID- 9013565
TI  - Expression and functional domains of rabbit liver UDP-glucuronosyltransferase
      2B16 and 2B13.
AB  - Southern blot analysis has demonstrated that the 5' portion of the rabbit liver
      dexamethasone-inducible UDP-glucuronosyltransferase (UGT) 2B13 RNA is related in
      sequence to a family of UGT genes (Tukey, R. H., Pendurthi, U. R., Nguyen, N. T.,
      Green, M. D., and Tephly, T. R. (1993) J. Biol. Chem. 268, 15260-15266). To
      identify these additional gene transcripts, rabbit liver cDNA libraries were
      screened with a 5' conserved 330-base pair UGT2B13 cDNA fragment, resulting in
      the isolation and characterization of several rabbit liver UGT cDNAs. One such
      clone, called pGT11, encodes a putative glycoprotein that is 78% similar to
      rabbit UGT2B13. The new UGT has been designated UGT2B16. The UGT2B16 gene is
      expressed as a single 4200-base RNA transcript that is regulated only in adult
      rabbits. The predicted NH2-terminal 25 amino acids of UGT2B16 are identical to
      that of rabbit liver UGT2B13, with the remainder of the protein being 77% similar
      to UGT2B13. Expressed UGT2B16 protein in COS-1 cells was active toward 4
      hydroxybiphenyl, similar to that of UGT2B13. However, UGT2B16 efficiently
      conjugated 4-hydroxyestrone and 4-tert-butylphenol, substrates that are not
      efficiently catalyzed by UGT2B13. To further characterize the structural domains
      of UGT2B16 and UGT2B13, a series of chimeric cDNAs were constructed that
      contained portions of both UGT2B16 and UGT2B13. Chimeric 2B163002B13531, which
      contained the amino-terminal UGT2B16 amino acids 1-300 followed by amino acids
      301-531 of UGT2B13, as well as chimeric 2B163582B13531 and 2B164342B13531
      proteins, catalyzed the glucuronidation of 4-hydroxyestrone, indicating that the
      carboxyl terminus of UGT2B13 could substitute for those same regions on UGT2B16.
      However, the replacement of the carboxyl end of UGT2B13 with 2B16300-531 or
      2B16434-531 dramatically impaired the catalytic function of the chimeric
      proteins. These results indicate that the carboxyl end of UGT2B13 plays an
      important role in the functional and possible conformational state of the
      protein.

PMID- 9013566
TI  - Structural features of alkylphenolic chemicals associated with estrogenic
      activity.
AB  - The ability of certain man-made chemicals to mimic the effects of natural steroid
      hormones and their potential to disrupt the delicate balance of the endocrine
      system in animals are of increasing concern. The growing list of reported hormone
      mimics includes the alkylphenolic (AP) compounds, a small number of which have
      been reported to be weakly estrogenic. In their most basic form, APs are composed
      of an alkyl group, which can vary in size, branching, and position, joined to a
      phenolic ring. The aim of this project was to identify the important structural
      features responsible for the estrogenic activity of AP chemicals. This was
      achieved by incubating APs with different structural features in a medium
      containing a previously described estrogen-inducible strain of yeast
      (Saccharomyces cerevisiae) expressing the human estrogen receptor and comparing
      their activity spectrophotometrically by the resulting color change of the
      medium. The results were compared to the effects of the main natural estrogen
      17beta-estradiol. The data indicate that both the position (para > meta > ortho)
      and branching (tertiary > secondary = normal) of the alkyl group affect
      estrogenicity. Optimal estrogenic activity requires a single tertiary branched
      alkyl group composed of between 6 and 8 carbons located at the para position on
      an otherwise unhindered phenol ring. The results are discussed in relation to the
      purity and composition of the chemicals tested.

PMID- 9013567
TI  - Multiple transcripts for rat nucleoside diphosphate kinase alpha isoform are
      structurally categorized into two groups that exhibit cell-specific expression
      and distinct translation potential.
AB  - Rat nucleoside diphosphate (NDP) kinase is composed of two isoforms (alpha and
      beta) encoded by independent genes. The mRNAs are expressed ubiquitously;
      however, the level of expression is tissue-dependent and is also up- or down
      regulated under certain conditions, including growth stimulation,
      differentiation, and tumor metastasis. To address the regulatory mechanisms of
      gene expression for the rat NDP kinase major isoform alpha (an nm23-H2/PuF
      homologue), we identified the transcription initiation sites in detail by RNase
      protection and 5'-rapid amplification of DNA ends and located the core promoter
      region by chloramphenicol acetyltransferase assay. The transcripts, initiated
      from an extraordinarily wide range of sites, were categorized into two groups;
      one transcribed from an upstream region was spliced in the untranslated region
      (group 1), whereas the other initiated in the downstream region was not (group
      2). RNase protection demonstrated that the group 1 mRNA was the dominant form
      present in all tissues except heart and skeletal muscle. In situ hybridization
      revealed cell-specific expression of these mRNA species. Furthermore, they
      differed in the translational efficiency (the group 2 alpha > beta > the group 1
      alpha). These findings suggest that the regulation of the NDP kinase expression
      at both transcriptional and posttranscriptional steps could be fundamentally
      governed by the selection of transcription initiation sites.

PMID- 9013568
TI  - Hemopoietic growth factors with the exception of interleukin-4 activate the p38
      mitogen-activated protein kinase pathway.
AB  - The mammalian mitogen-activated protein (MAP) kinase homologue p38 has been shown
      to be activated by pro-inflammatory cytokines as well as physical and chemical
      stresses. We now show that a variety of hemopoietic growth factors, including
      Steel locus factor, colony stimulating factor-1, granulocyte/macrophage-colony
      stimulating factor, and interleukin-3, activate p38 MAP kinase and the downstream
      kinase MAPKAP kinase-2. Furthermore, although these growth factors activate both
      p38 MAP kinase and Erk MAP kinases, we demonstrate using a specific inhibitor of
      p38 MAP kinase, SB 203580, that p38 MAP kinase activity was required for MAP
      kinase-activated protein kinase-2 activation. Conversely p38 MAP kinase was shown
      not to be required for in vivo activation of p90(rsk), known to be downstream of
      the Erk MAP kinases. Interleukin-4 was unique among the hemopoietic growth
      factors we examined in failing to induce activation of either p38 MAP kinase or
      MAP kinase-activated protein kinase-2. These findings demonstrate that the
      activation of p38 MAP kinase is involved not only in responses to stresses but
      also in signaling by growth factors that regulate the normal development and
      function of cells of the immune system.

PMID- 9013569
TI  - Binding of mammalian ribosomal protein complex P0.P1.P2 and protein L12 to the
      GTPase-associated domain of 28 S ribosomal RNA and effect on the accessibility to
      anti-28 S RNA autoantibody.
AB  - We have investigated binding of rat ribosomal proteins to the "GTPase domain" of
      28 S rRNA and its effect on accessibility to the anti-28 S autoantibody, which
      recognizes a unique tertiary structure of this RNA domain. Ribosomal protein L12
      and P protein complex (P complex) consisting of P0, P1, and P2 both bound to the
      GTPase domain of rat 28 S rRNA in a buffer containing Mg2. Chemical footprinting
      analysis of their binding sites revealed that the P complex mainly protected a
      conserved internal loop region comprising residues 1855-1861 and 1920-1922,
      whereas L12 protected an adjacent helix region encompassing residues 1867-1878
      and 1887-1899. These sites are close to but distinct from the binding site for
      anti-28 S antibody determined previously. The bindings of P complex and L12
      increased the anti-28 S accessibility, as revealed by gel retardation and
      quantitative immunoprecipitation analyses. In a Mg2+-eliminated condition, the
      RNA failed to bind to either anti-28 S or L12 but assembled into a complex under
      their coexistence. However, the RNA retained a property of binding to the P
      complex even in the absence of Mg2+, and this binding conferred high anti-28 S
      accessibility. These results indicated that the bindings of the P complex and L12
      to their respective sites influenced the GTPase domain to increase the
      accessibility to anti-28 S. A possible RNA conformation adjusted by the protein
      bindings is discussed.

PMID- 9013570
TI  - Influence of subunit interactions on lutropin specificity. Implications for
      studies of glycoprotein hormone function.
AB  - Bovine lutropin (bLH) and human chorionic gonadotropin (hCG) are heterodimeric
      glycoprotein hormones required for reproduction. Both bind rat LH receptors
      (rLHRs), but hCG binds human LH receptors (hLHRs) 1000-10,000 fold better than
      bLH. We tested the premise that this difference in affinity could be used to
      identify lutropin receptor contacts. Heterodimers containing hCG/bLH alpha- or
      beta-subunit chimeras that bound hLHR like hCG (or bLH) were expected to have hCG
      (or bLH) residues at the receptor contact sites. Analogs containing one subunit
      derived from hCG bound hLHR much more like hCG than bLH, indicating that each bLH
      subunit contains all the residues sufficient for high affinity hLHR binding.
      Indeed, the presence of bovine alpha-subunit residues increased the activities of
      some hCG analogs. The low hLHR activity of bLH was due primarily to an
      interaction between its alpha-subunit and beta-subunit residue Leu95. Leu95 does
      not appear to contact the hLHR since it did not influence the hLHR activity of
      heterodimers containing human alpha-subunit. These observations show that
      interactions within and between the subunits can significantly influence the
      activities of lutropins, thereby confounding efforts to identify ligand residues
      that contact these receptors.

PMID- 9013571
TI  - Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in
      leukocytes.
AB  - Anandamide (arachidonoylethanolamide, AnNH) and palmitoylethanolamide (PEA) have
      been proposed as the physiological ligands, respectively, of central and
      peripheral cannabinoid receptors. Both of these receptors are expressed in immune
      cells, including macrophages and mast cells/basophils, where immunomodulatory
      and/or anti-inflammatory actions of AnNH and PEA have been recently reported. We
      now provide biochemical grounds to these actions by showing that the
      biosynthesis, uptake, and degradation of AnNH and PEA occur in leukocytes. On
      stimulation with ionomycin, J774 macrophages and RBL-2H3 basophils produced AnNH
      and PEA, probably through the hydrolysis of the corresponding N
      acylphosphatidylethanolamines, also found among endogenous phospholipids.
      Immunological challenge of RBL-2H3 cells also caused AnNH and PEA release. The
      chemical structure and the amounts of AnNH and PEA produced upon ionomycin
      stimulation were determined by means of double radiolabeling experiments and
      isotope dilution gas chromatography/electron impact mass spectrometry. Both cell
      lines rapidly sequestered the two amides from the culture medium through
      temperature-dependent, saturable and chemically inactivable mechanisms. Once
      uptaken by basophils, AnNH and PEA compete for the same inactivating enzyme which
      catalyzes their hydrolysis to ethanolamine. This enzyme was found in both
      microsomal and 10,000 x g fractions of RBL cell homogenates, and exhibited
      similar inhibition and temperature/pH dependence profiles but a significantly
      higher affinity for PEA with respect to neuronal "anandamide amidohydrolase." The
      finding of biosynthetic and inactivating mechanisms for AnNH and PEA in
      macrophages and basophils supports the previously proposed role as local
      modulators of immune/inflammatory reactions for these two long chain
      acylethanolamides.

PMID- 9013572
TI  - Inhibition of carnitine palmitoyltransferase I augments sphingolipid synthesis
      and palmitate-induced apoptosis.
AB  - To identify cell death-induced genes, we employed a subtractive hybridization
      approach and isolated a cDNA encoding a mouse homolog of carnitine
      palmitoyltransferase I (CPT I), an enzyme that resides at the outer mitochondrial
      membrane and facilitates passage of long-chain fatty acids into mitochondria for
      beta-oxidation. Induced expression of CPT I mRNA was observed upon programmed
      cell death in the murine hematopoietic cell lines LyD9 and WEHI-231. To elucidate
      the role of CPT I in programmed cell death, we examined the effects of long-chain
      fatty acids and found that the addition of palmitate or stearate to cultured
      cells led to activation of a death program with a morphology resembling that of
      apoptosis. Other naturally occurring fatty acids, including myristate and
      palmitoleate, had no effect. Since both palmitate and stearate are sphingolipid
      precursors, the effect of these fatty acids on sphingolipid metabolism was
      tested. Our results indicate that apoptosis induced by palmitate or stearate is
      correlated with de novo synthesis of ceramide. Inhibition of CPT I by etomoxir
      enhanced palmitate-induced cell death and led to a further increase in ceramide
      synthesis.

PMID- 9013573
TI  - Cripto enhances the tyrosine phosphorylation of Shc and activates mitogen
      activated protein kinase (MAPK) in mammary epithelial cells.
AB  - Cripto-1 (CR-1), a recently discovered protein of the epidermal growth factor
      (EGF) family, was found to interact with a high affinity, saturable binding
      site(s) on HC-11 mouse mammary epithelial cells and on several different human
      breast cancer cell lines. This receptor exhibits specificity for CR-1, since
      other EGF-related peptides including EGF, transforming growth factor alpha,
      heparin-binding EGF-like growth factor, amphiregulin, epiregulin, betacellulin,
      or heregulin beta1 that bind to either the EGF receptor or to other type 1
      receptor tyrosine kinases such as erb B-3 or erb B-4 fail to compete for binding.
      Conversely, CR-1 was found not to directly bind to or to activate the tyrosine
      kinases associated with the EGFR, erb B-2, erb B-3, or erb B-4 either alone or in
      various pairwise combinations which have been ectopically expressed in Ba/F3
      mouse pro-B lymphocyte cells. However, exogenous CR-1 could induce an increase in
      the tyrosine phosphorylation of 185- and 120-kDa proteins and a rapid (within 3-5
      min) increase in the tyrosine phosphorylation of the SH2-containing adaptor
      proteins p66, p52, and p46 Shc in mouse mammary HC-11 epithelial cells and in
      human MDA-MB-453 and SKBr-3 breast cancer cells. CR-1 was also found to promote
      an increase in the association of the adaptor Grb2-guanine nucleotide exchange
      factor-mouse son of sevenless (mSOS) signaling complex with tyrosine
      phosphorylated Shc in HC-11 cells. Finally, CR-1 was able to increase p42(erk-2)
      mitogen-activated protein kinase (MAPK) activity in HC-11 cells within 5-10 min
      of treatment. These data demonstrate that CR-1 can function through a receptor
      which activates intracellular components in the ras/raf/MEK/MAPK pathway.

PMID- 9013574
TI  - Differential interaction of 1alpha,25-dihydroxyvitamin D3 analogues and their 20
      epi homologues with the vitamin D receptor.
AB  - An important focus of structure-function studies of synthetic ligands for the
      vitamin D receptor (VDR) concerns the chiral center at carbon 20 of the steroid
      side chain; 20-epi analogues are 100-10, 000 times more potent transcriptionally
      than the natural hormone 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3). We
      have compared the binding properties of three pairs of analogues either with a
      natural (N) or 20-epi (E) orientation. In intact cells, 45-60% of VDR.N-analogue
      complexes, but only 5-20% of VDR.E-analogue complexes, dissociated over a 3-h
      interval. The two groups of ligands induced distinct changes in VDR conformation
      as revealed by protease clipping assays. Mapping of ligand-VDR binding activity
      by deletions indicated that amino acids 420-427 were important for high affinity
      of VDR.N-analogue complexes, but not for VDR.E-analogue complexes. Site-directed
      mutagenesis revealed that residues 421 and 422 were essential for 1alpha,25
      (OH)2D3-induced conformational changes, high affinity of 1alpha,25-(OH)2D3 for
      VDR, and transcriptional activity, but not for binding of its 20-epi analogue. In
      contrast, deletion of residues 396-427 abolished binding of 1alpha,25-(OH)2D3,
      but binding of its 20-epi analogue was still detectable. The results suggest that
      the ligand-binding domain of VDR has multiple and different contact sites for the
      two families of side chain-modified ligands, resulting in VDR.ligand complexes
      with different half-lives and transcriptional activities.

PMID- 9013575
TI  - Oxidative stress, thiol reagents, and membrane potential modulate the
      mitochondrial permeability transition by affecting nucleotide binding to the
      adenine nucleotide translocase.
AB  - Stimulation of the mitochondrial permeability transition (MPT) in de-energized
      mitochondria by phenylarsine oxide (PheArs) is greater than that by diamide and t
      butylhydroperoxide (TBH), yet the increase in CyP binding to the inner
      mitochondrial membrane (Connern, C. P. and Halestrap, A. P. (1994) Biochem. J.
      302, 321-324) is less. From a range of nucleotides tested only ADP, deoxy-ADP,
      and ATP inhibited the MPT. ADP inhibition involved two sites with Ki values of
      about 1 and 25 microM which were independent of [Ca2+] and CyP binding.
      Carboxyatractyloside (CAT) abolished the high affinity site. Following
      pretreatment of mitochondria with TBH or diamide, the Ki for ADP increased to 50
      100 microM, whereas pretreatment with PheArs or eosin maleimide increased the Ki
      to >500 microM; only one inhibitory site was observed in both cases. Eosin
      maleimide is known to attack Cys159 of the adenine nucleotide translocase (ANT)
      in a CAT-sensitive manner (Majima, E., Shinohara, Y., Yamaguchi, N., Hong, Y. M.,
      and Terada, H. (1994) Biochemistry 33, 9530-9536), and here we demonstrate CAT
      sensitive binding of the ANT to a PheArs affinity column. In adenine nucleotide
      depleted mitochondria, no stimulation of the MPT by uncoupler was observed in the
      presence or absence of thiol reagents, suggesting that membrane potential may
      inhibit the MPT by increasing adenine nucleotide binding through an effect on the
      ANT conformation. We conclude that CsA and ADP inhibit pore opening in distinct
      ways, CsA by displacing bound CyP and ADP by binding to the ANT. Both mechanisms
      act to decrease the Ca2+ sensitivity of the pore. Thiol reagents and oxidative
      stress may modify two thiol groups on the ANT and thus stimulate pore opening by
      both means.

PMID- 9013576
TI  - Biotin sulfoxide reductase. Heterologous expression and characterization of a
      functional molybdopterin guanine dinucleotide-containing enzyme.
AB  - Rhodobacter sphaeroides f. sp. denitrificans biotin sulfoxide reductase has been
      heterologously expressed in Escherichia coli as a functional 106-kDa glutathione
      S-transferase fusion protein. Following cleavage with Factor Xa and purification
      to homogeneity, the soluble 83-kDa enzyme retained biotin sulfoxide reductase
      activity using reduced methyl viologen or reduced benzyl viologen as artificial
      electron donors. Initial rate kinetics indicated a specific activity at pH 8.0 of
      0.9 micromol of biotin sulfoxide reduced per min/nmol of enzyme and Km values of
      29 and 15 microM for reduced methyl viologen and biotin sulfoxide reductase,
      respectively. Biotin sulfoxide reductase was also capable of reducing
      nicotinamide N-oxide, methionine sulfoxide, trimethylamine-N-oxide, and dimethyl
      sulfoxide, although with varying efficiencies, and could directly utilize NADPH
      as a reducing agent, both for the reduction of biotin sulfoxide and ferricyanide.
      The enzyme contained the prosthetic group, molybdopterin guanine dinucleotide,
      and did not require any accessory proteins for functionality. These results
      represent the first successful heterologous expression and characterization of a
      functional molybdopterin guanine dinucleotide-containing enzyme and the
      demonstration of reduced pyridine nucleotide-dependent biotin sulfoxide reductase
      activity.

PMID- 9013577
TI  - Paracatalytic inactivation of L-2-haloacid dehalogenase from Pseudomonas sp. YL
      by hydroxylamine. Evidence for the formation of an ester intermediate.
AB  - Asp10 of L-2-haloacid dehalogenase from Pseudomonas sp. YL was proposed to act as
      a nucleophile to attack the alpha-carbon of L-2-haloalkanoic acids to form an
      ester intermediate, which is hydrolyzed by nucleophilic attack of a water
      molecule on the carbonyl carbon (Liu, J.-Q, Kurihara, T., Miyagi, M., Esaki, N.,
      and Soda, K. (1995) J. Biol. Chem. 270, 18309-18312). We have found that the
      enzyme is paracatalytically inactivated by hydroxylamine in the presence of the
      substrates monochloroacetate and L-2-chloropropionate. Ion spray mass
      spectrometry demonstrated that the molecular mass of the enzyme inactivated by
      hydroxylamine during the dechlorination of monochloroacetate is about 74 Da
      greater than that of the native enzyme. To determine the increase of the
      molecular mass more precisely, we digested the inactivated enzyme with lysyl
      endopeptidase and measured the molecular masses of the peptide fragments. The
      molecular mass of the hexapeptide Gly6-Lys11 was shown to increase by 73 Da.
      Tandem mass spectrometric analysis of this peptide revealed that the increase is
      due to a modification of Asp10. When the enzyme was paracatalytically inactivated
      by hydroxylamine during the dechlorination of L-2-chloropropionate, the molecular
      mass of the hexapeptide was 87 Da higher. Hydroxylamine is proposed to attack the
      carbonyl carbon of the ester intermediate and form a stable aspartate beta
      hydroxamate carboxyalkyl ester residue in the inactivated enzyme.

PMID- 9013578
TI  - Kinetics of fusion between endoplasmic reticulum vesicles in vitro.
AB  - The endoplasmic reticulum (ER) is a highly dynamic organelle, continuously
      undergoing membrane fusion and fission. We have measured homotypic fusion between
      ER vesicles isolated from Chinese hamster ovary cells kinetically in vitro, using
      an assay based on the metabolic incorporation of pyrene-labeled fatty acids into
      the phospholipids of cellular membranes. An increase in pyrene-monomer
      fluorescence was observed after mixing labeled and unlabeled ER vesicles in the
      presence of ATP and GTP. The protein, temperature, and nucleotide dependence of
      the increase indicated that it was caused by membrane fusion rather than
      molecular transfer of labeled lipids to unlabeled membranes. This assay allowed
      the first kinetic measurements with virtually nonexchangeable probes of a
      homotypic membrane fusion event. At 37 degrees C, fusion started off immediately
      at a rate of 1.14 +/- 0.29%/min and reached a half-maximal level after 56 min. In
      the presence of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), or after
      treatment of the membranes with N-ethylmaleimide, fusion was reduced but not
      completely inhibited. Addition of GTP during a fusion reaction immediately
      accelerated, and GTPgammaS immediately slowed down the fusion reaction. Thus,
      these kinetic measurements indicate that G-proteins might act to rapidly enhance
      fusion beyond a basic level.

PMID- 9013579
TI  - Interleukin-1-induced growth inhibition of human melanoma cells. Interleukin-1
      induced antizyme expression is responsible for ornithine decarboxylase activity
      down-regulation.
AB  - Interleukin (IL)-1 is a multi-functional cytokine and regulates cell growth
      either positively or negatively. Previous studies have shown that IL-1-induced
      ornithine decarboxylase (ODC) activity down-regulation is involved in the anti
      proliferative effect of IL-1 on human A375 melanoma cells. In this study, we
      examined the IL-1alpha-induced molecular events resulting in ODC activity down
      regulation in C2-1, a A375 cell line stably transfected with human type I IL-1
      receptor. Recombinant human (rh) IL-1alpha inhibited the growth and down
      regulated the ODC activity of C2-1 cells in a dose-dependent manner. Kinetics
      studies showed that both the DNA synthesis and ODC activity of C2-1 cells
      progressively decreased from 12 h after IL-1 addition. Northern hybridization
      showed that IL-1 had no influence on ODC mRNA level. However, rhIL-1 induced both
      a decrease of ODC protein and an ODC-inhibiting activity in IL-1-treated C2-1
      cells. IL-1 specifically up-modulated the mRNA level of antizyme, a protein
      essential for ODC regulation, but had little effect on its stability. IL-1
      induced antizyme up-modulation preceded IL-1-induced down-regulation of ODC
      protein, ODC activity, and DNA synthesis in C2-1 cells. Run-on transcription
      analysis confirmed that the increased antizyme mRNA expression was due to
      elevated antizyme gene transcription. Furthermore, the action of IL-1 to inhibit
      the ODC activity and growth of C2-1 cells was blocked by expressing the antisense
      RNA of human antizyme in C2-1 cells. These results suggest that IL-1-induced
      antizyme expression is responsible for IL-1-induced ODC activity down-regulation
      in human melanoma cells.

PMID- 9013580
TI  - Effect of amino acid substitutions on the activity of carnobacteriocin B2.
      Overproduction of the antimicrobial peptide, its engineered variants, and its
      precursor in Escherichia coli.
AB  - Carnobacteriocin B2, a 48-amino acid antimicrobial peptide containing a YGNGV
      motif that is produced by the lactic acid bacterium Carnobacterium piscicola
      LV17B, was overexpressed as fusion with maltose-binding protein in Escherichia
      coli. This fusion protein was cleaved with Factor Xa to allow isolation of the
      mature bacteriocin that was identical in all respects to that obtained from C.
      piscicola. Similar methodology permitted production of the precursor
      precarnobacteriocin B2 (CbnB2P), which has an 18-amino acid leader, as well as
      six mutants of the mature peptide: CbnF3 (Tyr3 --> Phe), CbnS33 (Phe33 --> Ser),
      CbnI34 (Val34 --> Ile), CbnI37 (Val37 --> Ile), CbnG46 (Arg46 --> Gly), and Cbn28
      (truncated frameshift mutation: (carnobacteriocin B2 1-28) + ELTHL). Examination
      of these compounds for antimicrobial activity showed that although CbnI34,
      CbnI37, and CbnG46 were fully active, CbnB2P, CbnF3, CbnS33, Cbn28, and all of
      the fusion proteins had greatly reduced or no antimicrobial activity. Expression
      of the immunity protein that protects against the action of the parent
      carnobacteriocin B2 in a previously sensitive organism also protects against the
      active mutants. Because carnobacteriocin B2 also acts as an inducer of
      bacteriocin production in C. piscicola, the ability of the precursor CbnB2P and
      the mutants to exert this effect was examined. All were able to induce Bac-
      cultures and reestablish the Bac+ phenotype except for the truncated Cbn28. The
      results demonstrate that very minor changes in the peptide sequence may
      drastically alter antimicrobial activity but that the induction of bacteriocin
      production is much more tolerant of structural modification, especially at the N
      terminus.

PMID- 9013581
TI  - Kinetic control of the dissociation pathway of calmodulin-peptide complexes.
AB  - The mechanism of dissociation reactions induced by calcium chelators has been
      studied for complexes of Drosophila calmodulin with target peptides, including
      four derived from the skeletal muscle myosin light chain kinase target sequence.
      Reactions were monitored by fluorescence stopped-flow techniques using a variety
      of intrinsic probes and the indicator Quin2. For most of the complexes,
      apparently biphasic kinetics were observed in several fluorescence parameters.
      The absence of any obvious relationship between dissociation rates and peptide
      affinities implies kinetic control of the dissociation pathway. A general
      mechanism for calcium and peptide dissociation was formulated and used in
      numerical simulation of the experimental data. Unexpectedly, the rate of the
      slowest step decreases with increasing [peptide]/[calmodulin] ratio. Numerical
      simulation shows this step could contain a substantial contribution from a
      reversible relaxation process (involving the species Ca2-calmodulin-peptide),
      convolved with the following step (loss of C-terminal calcium ions). The results
      indicate the potentially key kinetic role of the partially calcium-saturated
      intermediate species. They show that subtle changes in the peptide sequence can
      have significant effects on both the dissociation rates and also the dissociation
      pathway. Both effects could contribute to the variety of regulatory behavior
      shown by calmodulin with different target enzymes.

PMID- 9013582
TI  - The Oct-1 POU homeodomain stabilizes the adenovirus preinitiation complex via a
      direct interaction with the priming protein and is displaced when the replication
      fork passes.
AB  - Initiation of adenovirus DNA replication is strongly enhanced by two cellular
      transcription factors, NFI and Oct-1, which bind to the auxiliary origin and
      tether the viral precursor terminal protein-DNA polymerase (pTP.pol) complex to
      the core origin. NFI acts through a direct contact with the DNA polymerase, but
      the mode of action of Oct 1 is unknown. Employing glutathione S-transferase-POU
      pull-down assays and protein affinity chromatography, we have established that
      the POU domain contacts pTP rather than pol. The POU homeodomain is responsible
      for this interaction. The protein-protein contacts lead to increased binding of
      pTP-pol to the core origin, which is caused by a reduced off-rate. The enhanced
      formation of a pTP.pol.POU complex on the origin correlates with stimulation of
      replication. Using an immobilized replication system, we have studied the
      kinetics of dissociation of the Oct-1 POU domain during replication. In contrast
      to NFI, which dissociates very early in initiation, Oct-1 dissociates only when
      the binding site is rendered single-stranded upon translocation of the
      replication fork. Our data indicate that NFI and Oct-1 enhance initiation
      synergistically by touching different targets in the preinitiation complex and
      dissociate independently after initiation.

PMID- 9013583
TI  - Peroxisome proliferator-activated receptors alpha and gamma are activated by
      indomethacin and other non-steroidal anti-inflammatory drugs.
AB  - Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) and cyclooxygenase
      inhibitor that is frequently used as a research tool to study the process of
      adipocyte differentiation. Treatment of various preadipocyte cell lines with
      micromolar concentrations of indomethacin in the presence of insulin promotes
      their terminal differentiation. However, the molecular basis for the adipogenic
      actions of indomethacin had remained unclear. In this report, we show that
      indomethacin binds and activates peroxisome proliferator-activated receptor gamma
      (PPARgamma), a ligand-activated transcription factor known to play a pivotal role
      in adipogenesis. The concentration of indomethacin required to activate PPARgamma
      is in good agreement with that required to induce the differentiation of
      C3H10T1/2 cells to adipocytes. We demonstrate that several other NSAIDs,
      including fenoprofen, ibuprofen, and flufenamic acid, are also PPARgamma ligands
      and induce adipocyte differentiation of C3H10T1/2 cells. Finally, we show that
      the same NSAIDs that activate PPARgamma are also efficacious activators of
      PPARalpha, a liver-enriched PPAR subtype that plays a key role in peroxisome
      proliferation. Interestingly, several NSAIDs have been reported to induce
      peroxisomal activity in hepatocytes both in vitro and in vivo. Our findings
      define a novel group of PPARgamma ligands and provide a molecular basis for the
      biological effects of these drugs on adipogenesis and peroxisome activity.

PMID- 9013584
TI  - Interactions of a subassembly of the herpes simplex virus type 1 helicase-primase
      with DNA.
AB  - The UL5, UL8, and UL52 genes of herpes simplex virus type 1 encode a multisubunit
      assembly that possesses primase, DNA helicase, and DNA-dependent nucleoside
      triphosphatase activities. A subassembly consisting of the UL5 and UL52 gene
      products retains these activities. The nucleoside triphosphatase activity of the
      UL5/UL52 subassembly is strongly stimulated by both homo- and heteropolymeric
      single-stranded DNA. Double-stranded DNA has little ability to stimulate the
      ATPase activity. The subassembly binds both double and single-stranded DNA.
      Nucleotides are not required for DNA-binding. The minimum length of single
      stranded DNA that is bound and that stimulates enzymatic activity is about 12
      nucleotides. The kinetic parameters of the ATPase activity of the subassembly are
      affected by the length of the oligonucleotide coeffector. The Km decreases as the
      coeffector length is increased up to a length of about 20 nucleotides and then
      remains independent of coeffector length. The first order rate constant for
      ATPase activity exhibits a quasihyperbolic dependence on the length of the DNA
      coeffector and is maximal for coeffectors of 20 nucleotides and longer.

PMID- 9013585
TI  - Properties and kinetic analysis of UDP-glucose dehydrogenase from group A
      streptococci. Irreversible inhibition by UDP-chloroacetol.
AB  - UDP-glucuronic acid is used by many pathogenic bacteria in the construction of an
      antiphagocytic capsule that is required for virulence. The enzyme UDP-glucose
      dehydrogenase catalyzes the NAD+-dependent 2-fold oxidation of UDP-glucose and
      provides a source of the acid. In the present study the recombinant dehydrogenase
      from group A streptococci has been purified and found to be active as a monomer.
      The enzyme contains no chromophoric cofactors, and its activity is unaffected by
      the presence of EDTA or carbonyl-trapping reagents. Initial velocity and product
      inhibition kinetic patterns are consistent with a bi-uni-uni-bi ping-pong
      mechanism in which UDP-glucose is bound first and UDP-glucuronate is released
      last. UDP-xylose was found to be a competitive inhibitor (Ki, 2.7 microM) of the
      enzyme. The enzyme is irreversibly inactivated by uridine 5'-diphosphate
      chloroacetol due to the alkylation of an active site cysteine thiol. The apparent
      second order rate constant for the inhibition (ki/Ki) was found to be 2 x 10(3)
      mM-1 min-1. Incubation with the truncated compound, chloroacetol phosphate,
      resulted in no detectable inactivation when tested under comparable conditions.
      This supports the notion that uridine 5'-diphosphate-chloroacetol is bound in the
      place of UDP-glucose and is not simply acting as a nonspecific alkylating agent.

PMID- 9013586
TI  - Parathyroid hormone activates mitogen-activated protein kinase via a cAMP
      mediated pathway independent of Ras.
AB  - In a previous study, we demonstrated that parathyroid hormone (PTH) inhibits
      mitogen-activated protein (MAP) kinase activation in osteosarcoma cells via a
      protein kinase A-dependent pathway. Here, we show that PTH can induce a transient
      activation of MAP kinase as well. This was observed in both Chinese hamster ovary
      R15 cells stably expressing high levels of rat PTH/PTH-related peptide receptor
      and parietal yolk sac carcinoma cells expressing the receptor endogenously. PTH
      was a strong activator of adenylate cyclase and phospholipase C in Chinese
      hamster ovary R15 cells. PTH-induced MAP kinase activation did not depend on
      activation of Gi, phorbol ester-sensitive protein kinase C, elevated
      intracellular calcium levels, or release of Gbetagamma subunits. It could,
      however, be mimicked by addition of forskolin or 8-bromo-cAMP to these cells.
      Prolonged treatment with forskolin caused sustained protein kinase A activity,
      whereas MAP kinase activity returned to basal levels. Subsequent treatment with
      PTH or 8-bromo-cAMP did not result in MAP kinase activation, whereas phorbol
      ester- or insulin-induced MAP kinase activation was unaffected. Finally,
      expression of a dominant negative form of Ras (RasAsn-17), which completely
      blocked insulin-induced MAP kinase activation, did not affect activation by PTH
      or cAMP. In conclusion, PTH regulates MAP kinase activity in a cell type-specific
      fashion. The activation of MAP kinase by PTH is mediated by cAMP and independent
      of Ras.

PMID- 9013587
TI  - Transcriptional regulation of the human PAX6 gene promoter.
AB  - PAX6, a member of the highly conserved paired-type homeobox gene family, is
      expressed in a spatially and temporally restricted pattern during early
      embryogenesis, and its mutation is responsible for human aniridia. Here we
      examined the transcriptional regulation of the PAX6 gene by transient
      transfection assays and identified multiple cis-regulatory elements that function
      differently in different cell lines. The transcriptional initiation site was
      identified by RNase protection and primer extension assay. Examination of the
      genomic DNA sequence indicated that the PAX6 promoter has a TATA like-box
      (ATATTTT) at -26 base pairs (bp), and two CCAAT boxes are positioned at -70 and 
      100 bp. A 38-bp poly(CA) sequence was located 992 bp upstream from the initiation
      site. Transient transfection assays in glioblastoma cells and leukemia cells
      indicate that a 92-bp region was required for basal level PAX6 promoter activity.
      A negative transcriptional element, silencer (bases -1518 to -1268), functioned
      differently in different cell lines. The activation of the promoter is positively
      correlated with the expression of PAX6 transcripts in all cells tested. These
      results indicate that a cis-regulatory element or elements is responsible for
      selective activation of the PAX6 promoter in cells that can express PAX6 mRNA.

PMID- 9013588
TI  - Isolation, purification, and characterization of amadoriase isoenzymes (fructosyl
      amine-oxygen oxidoreductase EC 1.5.3) from Aspergillus sp.
AB  - Four "amadoriase" enzyme fractions, which oxidatively degrade glycated low
      molecular weight amines and amino acids under formation of hydrogen peroxide and
      glucosone, were isolated from an Aspergillus sp. soil strain selected on
      fructosyl adamantanamine as sole carbon source. The enzymes were purified to
      homogeneity using a combination of ion exchange, hydroxyapatite, gel filtration,
      and Mono Q column chromatography. Molecular masses of amadoriase enzymes Ia, Ib,
      and Ic were 51 kDa, and 49 kDa for amadoriase II. Apparent kinetic constants for
      Nepsilon-fructosyl Nalpha-t-butoxycarbonyl lysine and fructosyl adamantanamine
      were almost identical for enzymes Ia, Ib, and Ic, but corresponding values for
      enzyme II were significantly different. FAD was identified in all enzymes based
      on its typical absorption spectrum. N-terminal sequence was identical for enzymes
      Ia and Ib (Ala-Pro-Ser-Ile-Leu-Ser-Thr-Glu-Ser-Ser-Ile-Ile-Val-Ile-Gly-Ala-Gly-
      Thr-Trp-Gly-) and Ic except that the first 5 amino acids were truncated. The
      sequence of enzyme II was different (Ala-Val-Thr-Lys-Ser-Ser-Ser-Leu-Leu-Ile-Val
      Gly-Ala-Gly-Thr-Trp-Gly- Thr-Ser-Thr-). All enzymes had the FAD cofactor-binding
      consensus sequence Gly-X-Gly-X-X-Gly within the N-terminal sequence. In summary,
      these data show the presence of two distinct amadoriase enzymes in the
      Aspergillus sp. soil strain selected on fructosyl adamantanamine and induced by
      fructosyl propylamine. In contrast to previous described enzymes, these novel
      amadoriase enzymes can deglycate both glycated amines and amino acids.

PMID- 9013589
TI  - Characterization of hepatic-specific regulatory elements in the promoter region
      of the human cholesterol 7alpha-hydroxylase gene.
AB  - Cholesterol 7alpha-hydroxylase is the rate-limiting enzyme in the degradation of
      cholesterol to bile salts and plays a central role in regulating cholesterol
      homeostasis. The mechanisms involved in the transcriptional control of the human
      gene are largely unknown. HepG2 cells represent an appropriate model system for
      the study of the regulation of the gene. To identify liver-specific DNA sequences
      in the promoter of the human CYP7 gene, we first examined the DNase I
      hypersensitivity in the 5'-region of the gene. An area of hypersensitivity was
      observed in the region from -50 to -200 of the human gene in nuclei from
      transcriptionally active HepG2 cells, but was absent in transcriptionally
      inactive HeLa cell nuclei or in free DNA. Various 5'-promoter deletion constructs
      were made and transfected into HepG2 cells. About 300 base pairs of upstream
      sequence are required for high level promoter activity of the human CYP7 gene in
      HepG2 cells. DNase I footprinting of the hypersensitive region revealed nine
      protected sequences. Gel retardation experiments demonstrated binding of HNF-3 to
      the segment from -80 to -70 and of hepatocyte nuclear factor HNF-4 (and ARP-1) to
      the segment from -148 to -127 of the human CYP7 promoter. Deletion of either of
      these sites depressed promoter activity in HepG2 cells. A third region from -313
      to -285 is bound by members of the HNF-3 family and acts as an enhancer.
      Additionally, the segment from -197 to -173 binds a negative regulatory protein
      that is present in Chinese hamster ovary cell extracts and in HepG2 cell
      extracts. These experiments define the key control elements responsible for basal
      transcription of the human CYP7 gene in HepG2 cells.

PMID- 9013590
TI  - Novel zinc-containing ferredoxin family in thermoacidophilic archaea.
AB  - The dicluster-type ferredoxins from the thermoacidophilic archaea such as
      Thermoplasma acidophilum and Sulfolobus sp. are known to contain an unusually
      long extension of unknown function in the N-terminal region. Recent x-ray
      structural analysis of the Sulfolobus ferredoxin has revealed the presence of a
      novel zinc center, which is coordinated by three histidine ligand residues in the
      N-terminal region and one aspartate in the ferredoxin core domain. We report here
      the quantitative metal analyses together with electron paramagnetic resonance and
      resonance Raman spectra of T. acidophilum ferredoxin, demonstrating the presence
      of a novel zinc center in addition to one [3Fe-4S] and one [4Fe-4S] cluster
      (Fe/Zn = 6.8 mol/mol). A phylogenetic tree constructed for several archaeal
      monocluster and dicluster type ferredoxins suggests that the zinc-containing
      ferredoxins of T. acidophilum and Sulfolobus sp. form an independent subgroup,
      which is more distantly related to the ferredoxins from the hyperthermophiles
      than those from the methanogenic archaea, indicating the existence of a novel
      group of ferredoxins, namely, a "zinc-containing ferredoxin family" in the
      thermoacidophilic archaea. Inspection of the N-terminal extension regions of the
      archaeal zinc-containing ferredoxins suggested strict conservation of three
      histidine and one aspartate residues as possible ligands to the novel zinc
      center.

PMID- 9013591
TI  - Cooperative exosite-dependent cleavage of synaptobrevin by tetanus toxin light
      chain.
AB  - The light chain (L chain) of tetanus neurotoxin (TeNT) has been shown to have
      been endowed with zinc endopeptidase activity, selectively directed toward the
      Gln76-Phe77 bond of synaptobrevin, a vesicle-associated membrane protein (VAMP)
      critically involved in neuroexocytosis. In previous reports, truncations at the
      NH2 and COOH terminus of synaptobrevin have shown that the sequence 39-88 of
      synaptobrevin is the minimum substrate of TeNT, suggesting either the requirement
      of a well defined three-dimensional structure of synaptobrevin or a role in the
      mechanism of substrate hydrolysis for residues distal from the cleavage site. In
      this study, the addition of NH2- and COOH-terminal peptides of synaptobrevin, S
      27-55 (S1) and S 82-93 (S2), to the synaptobrevin fragment S 56-81 allowed the
      cleavage of this latter peptide by TeNT to occur. This appears to result from an
      activation process mediated by the simultaneous binding of S1 and S2 with
      complementary sites present on TeNT as shown by surface plasmon resonance
      experiments and the determination of kinetic constants. All these results favor
      an exosite-controlled hydrolysis of synaptobrevin by TeNT, probably involving a
      conformational change of the toxin. This could account for the high degree of
      substrate specificity of TeNT and, probably, botulinum neurotoxins.

PMID- 9013592
TI  - Metabolic fate of peroxynitrite in aqueous solution. Reaction with nitric oxide
      and pH-dependent decomposition to nitrite and oxygen in a 2:1 stoichiometry.
AB  - Peroxynitrite, the reaction product of nitric oxide (NO) and superoxide (O-2) is
      assumed to decompose upon protonation in a first order process via intramolecular
      rearrangement to NO3-. The present study was carried out to elucidate the origin
      of NO2- found in decomposed peroxynitrite solutions. As revealed by stopped-flow
      spectroscopy, the decay of peroxynitrite followed first-order kinetics and
      exhibited a pKa of 6.8 +/- 0.1. The reaction of peroxynitrite with NO was
      considered as one possible source of NO2-, but the calculated second order rate
      constant of 9.1 x 10(4) M-1 s-1 is probably too small to explain NO2- formation
      under physiological conditions. Moreover, pure peroxynitrite decomposed to NO2-
      without apparent release of NO. Determination of NO2- and NO3- in solutions of
      decomposed peroxynitrite showed that the relative amount of NO2- increased with
      increasing pH, with NO2- accounting for about 30% of decomposition products at pH
      7.5 and NO3- being the sole metabolite at pH 3.0. Formation of NO2- was
      accompanied by release of stoichiometric amounts of O2 (0.495 mol/mol of NO2-).
      The two reactions yielding NO2- and NO3- showed distinct temperature dependences
      from which a difference in Eact of 26.2 +/- 0.9 kJ mol-1 was calculated. The
      present results demonstrate that peroxynitrite decomposes with significant rates
      to NO2- plus O2 at physiological pH. Through formation of biologically active
      intermediates, this novel pathway of peroxynitrite decomposition may contribute
      to the physiology and/or cytotoxicity of NO and superoxide.

PMID- 9013593
TI  - Hepatocyte growth factor alters the polarity of Madin-Darby canine kidney cell
      monolayers.
AB  - Hepatocyte growth factor (HGF) and E-cadherin are important for epithelial
      morphogenetic events. We examined the effects of HGF on E-cadherin localization
      and interaction with beta-catenin in polarized Madin-Darby canine kidney (MDCK)
      cell monolayers grown on filters. Surface biotinylation experiments showed that
      HGF increases apically accessible E-cadherin. Confocal immunofluorescence
      microscopy of HGF-treated cells showed localization of E-cadherin at membrane
      domains contacting the apical compartment and an increase in accessibility of
      apically applied antibodies to lateral E-cadherin below the tight junction.
      Coimmunoprecipitation of beta-catenin/E-cadherin complexes showed that the amount
      of E-cadherin associated with beta-catenin increased during the first 24 h of HGF
      treatment with a return to baseline values after 48 and 72 h. Metabolic labeling
      showed that HGF increased the synthetic rate of beta-catenin and the amount of
      newly synthesized E-cadherin associated with immunoprecipitated beta-catenin,
      with the peak effect occurring after 12 h of treatment and returning to baseline
      after 24 h. HGF treatment inhibited transcytosis of immunoglobulin A by the
      polymeric immunoglobulin receptor. We conclude that HGF treatment of polarized
      MDCK cells grown on filters decreases cell polarity and alters E-cadherin/beta
      catenin interaction and synthesis.

PMID- 9013594
TI  - Assembly of human hemoglobin. Studies with Escherichia coli-expressed alpha
      globin.
AB  - The alpha-globin of human hemoglobin was expressed in Escherichia coli and was
      refolded with heme in the presence and in the absence of native beta-chains. The
      functional and structural properties of the expressed alpha-chains were assessed
      in the isolated state and after assembly into a functional hemoglobin tetramer.
      The recombinant and native hemoglobins were essentially identical on the basis of
      sensitivity to effectors (Cl- and 2,3-diphosphoglycerate), Bohr effect, CO
      binding kinetics, dimer-tetramer association constants, circular dichroism
      spectra of the heme region, and nuclear magnetic resonance of the residues in the
      alpha1beta1 and alpha1beta2 interfaces. However, the nuclear magnetic resonance
      revealed subtle differences in the heme region of the expressed alpha-chain, and
      the recombinant human normal adult hemoglobin (HbA) exhibited a slightly
      decreased cooperativity relative to native HbA. These results indicate that
      subtle conformational changes in the heme pocket can alter hemoglobin
      cooperativity in the absence of modifications of quaternary interface contacts or
      protein dynamics. In addition to incorporation into a HbA tetramer, the alpha
      globin refolds and incorporates heme in the absence of the partner beta-chain.
      Although the CO binding kinetics of recombinant alpha-chains were the same as
      that of native alpha-chains, the ellipticity of the Soret circular dichroism
      spectrum was decreased and CO binding kinetics revealed an additional faster
      component. These results show that recombinant alpha-chain assumes alternating
      conformations in the absence of beta-chain and indicate that the isolated alpha
      chain exhibits a higher degree of conformational flexibility than the alpha-chain
      incorporated into the hemoglobin tetramer. These findings demonstrate the utility
      of the expressed alpha-globin as a tool for elucidating the role of this chain in
      hemoglobin structure-function relationships.

PMID- 9013595
TI  - Recognition of the -10 promoter sequence by a partial polypeptide of sigma70 in
      vitro.
AB  - Promoter recognition by RNA polymerase depends upon its ability to bind to
      specific DNA sequences. The sigma (sigma) subunit provides selectivity for
      transcription initiation by interacting with the -10 and -35 elements of promoter
      DNA. Suppressor mutations in sigma factor that compensate for specific "down"
      substitutions in the promoter have demonstrated that sigma factor recognizes
      certain base pairs of the promoter. Since these suppressors were only identified
      for changes at the -12 and -11 positions of the -10 element (TATAAT), the role of
      the other base pairs of this region in specifying recognition by sigma factor
      remained unclear. Using a partial polypeptide of sigma70 carrying regions 2-4,
      this report shows that the first three positions of the -10 element (-12, -11, 
      10) are important for sigma factor alone to recognize and bind to duplex DNA. The
      sigma polypeptide also binds to an "extended -10" promoter, even without a -35
      element. A mismatch bubble from -10 to +3 is bound regardless of the sequence
      within the bubble, or the presence or absence of a -35 element. Unexpectedly,
      binding to a mismatch bubble that lacks a -35 hexamer is sensitive to the
      identity of the -11 position, but not the -12 position.

PMID- 9013596
TI  - Purification and characterization of the small subunit of phage T4 terminase,
      gp16, required for DNA packaging.
AB  - Phage T4 terminase is an enzyme that binds to the portal protein of proheads and
      cuts and packages concatemeric DNA. The T4 terminase is composed of two subunits,
      gene products (gp) 16 and 17. The role of the small subunit, gp16, in T4 DNA
      packaging is not well characterized. We developed a new purification procedure to
      obtain large quantities of purified gp16 from an overexpression vector. The pure
      protein is found in two molecular weight forms, due to specific C-terminal
      truncation, displays in vitro packaging activity, and binds but does not
      hydrolyze ATP. gp16 forms specific oligomers, rings, and side-by-side double
      rings, as judged by native polyacrylamide gel electrophoresis and scanning
      transmission electron microscopy measurements. The single ring contains about
      eight monomers, and the rings have a diameter of about 8 nm with a central hole
      of about 2 nm. A DNA-binding helix-turn-helix motif close to the N terminus of
      gp16 is predicted. The oligomers do not bind to DNA, but following denaturation
      and renaturation in the presence of DNA, binding can be demonstrated by gel shift
      and filter binding assays. gp16 binds to double-stranded DNA but not single
      stranded DNA, and appears to bind preferentially to a gene 16-containing DNA
      sequence.

PMID- 9013597
TI  - Expression and activity of mutants of fasciculin, a peptidic acetylcholinesterase
      inhibitor from mamba venom.
AB  - Fasciculin, a selective peptidic inhibitor of acetylcholinesterase, is a member
      of the three-fingered peptide toxin superfamily isolated from snake venoms. The
      availability of a crystal structure of a fasciculin 2 (Fas2)-acetylcholinesterase
      complex affords an opportunity to examine in detail the interaction of this toxin
      with its target site. To this end, we constructed a synthetic fasciculin gene
      with an appropriate leader peptide for expression and secretion from mammalian
      cells. Recombinant wild-type Fas2, expressed and amplified in Chinese hamster
      ovary cells, was purified to homogeneity and found to be identical in composition
      and biological activities to the venom-derived toxin. Sixteen mutations at
      positions where the crystal structure of the complex indicates a significant
      interfacial contact point or determinant of conformation were generated. Two
      mutants of loop I, T8A/T9A and R11Q, ten mutants of the longest loop II, R24T,
      K25L, R27W, R28D, H29D, DeltaPro30, P31R, K32G, M33A, and V34A/L35A, and two
      mutants of loop III, D45K and K51S, were expressed transiently in human embryonic
      kidney cells. Inhibitory potencies of the Fas2 mutants toward mouse AChE were
      established, based on titration of the mutants with a polyclonal anti-Fas2 serum.
      The Arg27, Pro30, and Pro31 mutants each lost two or more orders of magnitude in
      Fas2 activity, suggesting that this subset of three residues, at the tip of loop
      II, dominates the loop conformation and interaction of Fas2 with the enzyme. The
      Arg24, Lys32, and Met33 mutants lost about one order of magnitude, suggesting
      that these residues make moderate contributions to the strength of the complex,
      whereas the Lys25, Arg28, Val34-Leu35, Asp45, and Lys51 mutants appeared as
      active as Fas2. The Thr8-Thr9, Arg11, and His29 mutants showed greater ratios of
      inhibitory activity to immunochemical titer than Fas2. This may reflect
      immunodominant determinants in these regions or intramolecular rearrangements in
      conformation that enhance the interaction. Of the many Fas2 residues that lie at
      the interface with acetylcholinesterase, only a few appear to provide substantial
      energetic contributions to the high affinity of the complex.

PMID- 9013598
TI  - Identification of N-linked glycosylation sites in human testis angiotensin
      converting enzyme and expression of an active deglycosylated form.
AB  - The sites of glycosylation of Chinese hamster ovary cell expressed testicular
      angiotensin-converting enzyme (tACE) have been determined by matrix-assisted
      laser desorption ionization/time of flight/mass spectrometry of peptides
      generated by proteolytic and cyanogen bromide digestion. Two of the seven
      potential N-linked glycosylation sites, Asn90 and Asn109, were found to be fully
      glycosylated by analysis of peptides before and after treatment with a series of
      glycosidases and with endoproteinase Asp-N. The mass spectra of the glycopeptides
      exhibit characteristic clusters of peaks which indicate the N-linked glycans in
      tACE to be mostly of the biantennary, fucosylated complex type. This structural
      information was used to demonstrate that three other sites, Asn155, Asn337, and
      Asn586, are partially glycosylated, whereas Asn72 appears to be fully
      glycosylated. The only potential site that was not modified is Asn620. Sequence
      analysis of tryptic peptides obtained from somatic ACE (human kidney) identified
      six glycosylated and one unglycosylated Asn. Only one of these glycosylation
      sites had a counterpart in tACE. Comparison of the two proteins reveals a pattern
      in which amino-terminal N-linked sites are preferred. The functional significance
      of glycosylation was examined with a tACE mutant lacking the O-glycan-rich first
      amino-terminal 36 residues and truncated at Ser625. When expressed in the
      presence of the alpha-glucosidase I inhibitor N-butyldeoxynojirimycin and treated
      with endoglycosidase H to remove all but the terminal N-acetylglucosamine
      residues, it retained full enzymatic activity, was electrophoretically
      homogeneous, and is a good candidate for crystallographic studies.

PMID- 9013599
TI  - Mass spectrometric quantification of markers for protein oxidation by tyrosyl
      radical, copper, and hydroxyl radical in low density lipoprotein isolated from
      human atherosclerotic plaques.
AB  - Lipoprotein oxidation has been implicated in the pathogenesis of atherosclerosis.
      However, the physiologically relevant pathways mediating oxidative damage have
      not yet been identified. Three potential mechanisms are tyrosyl radical, hydroxyl
      radical, and redox active metal ions. Tyrosyl radical forms o,o'-dityrosine cross
      links in proteins. The highly reactive hydroxyl radical oxidizes phenylalanine
      residues to o-tyrosine and m-tyrosine. Metal ions oxidize low density lipoprotein
      (LDL) by poorly understood pathways. To explore the involvement of tyrosyl
      radical, hydroxyl radical, and metal ions in atherosclerosis, we developed a
      highly sensitive and quantitative method for measuring levels of o, o'
      dityrosine, o-tyrosine, and m-tyrosine in proteins, lipoproteins, and tissue,
      using stable isotope dilution gas chromatography-mass spectrometry. We showed
      that o,o'-dityrosine was selectively produced in LDL oxidized with tyrosyl
      radical. Both o-tyrosine and o, o'-dityrosine were major products when LDL was
      oxidized with hydroxyl radical. Only o-tyrosine was formed in LDL oxidized with
      copper. Similar profiles of oxidation products were observed in bovine serum
      albumin oxidized with the three different systems. Applying these findings to LDL
      isolated from human atherosclerotic lesions, we detected a 100-fold increase in
      o,o'-dityrosine levels compared to those in circulating LDL. In striking
      contrast, levels of o-tyrosine and m-tyrosine were not elevated in LDL isolated
      from atherosclerotic tissue. Analysis of fatty streaks revealed a similar pattern
      of oxidation products; compared with normal aortic tissue, there was a selective
      increase in o,o'-dityrosine with no change in o-tyrosine. The detection of a
      selective increase of o,o'-dityrosine in LDL isolated from vascular lesions is
      consistent with the hypothesis that oxidative damage in human atherosclerosis is
      mediated in part by tyrosyl radical. In contrast, these observations do not
      support a role for free metal ions as catalysts of LDL oxidation in the artery
      wall.

PMID- 9013600
TI  - Influence of pyruvic acid methyl ester on rat pancreatic islets. Effects on
      insulin secretion, phosphoinositide hydrolysis, and sensitization of the beta
      cell.
AB  - The methyl ester of pyruvic acid (methyl pyruvate) stimulated a dose-dependent
      increase in insulin secretion from isolated perifused rat islets. The threshold
      level for release was about 10 mM, and at 20 mM the addition of MP to perifused
      islets resulted in a large first phase of secretion followed by an insulin
      secretory response that was sustained for at least 40 min. When compared to the
      effects of 20 mM glucose, peak first-phase release rates in response to 20 mM
      methyl pyruvate were comparable, but the second phase of release was only about
      10-15% of that observed with an equimolar level of the hexose. The stimulatory
      effects of 20 mM methyl pyruvate on secretion were abolished by the K1+-ATP
      channel blocker diazoxide (200 microM) and by the calcium channel antagonist
      nitrendipine (500 nM). The glucokinase inhibitor mannoheptulose (20 mM) had no
      adverse effect on the secretory response to 20 mM methyl pyruvate, whereas 10
      microM forskolin amplified the insulinotropic action of MP. Sodium pyruvate alone
      or in combination with 10 microM forskolin had no insulinotropic effect. In
      additional experiments islet phosphoinositide pools were labeled with myo-2
      [3H]inositol, and the subsequent accumulation of labeled inositol phosphates was
      used to monitor the activation of phospholipase C. Methyl pyruvate stimulated a
      dose-dependent increase in inositol phosphate levels when measured after a 30-min
      incubation period with a maximal increase of about 300% at 20 mM methyl pyruvate.
      The increase in phosphoinositide hydrolysis caused by methyl pyruvate (20 mM)
      was, like insulin secretion, reduced by both diazoxide and nitrendipine but was
      immune to inhibition by mannoheptulose. Pyruvate (20 mM) had no effect on
      inositol phosphate accumulation. Prior short-term exposure to methyl pyruvate
      sensitized islets to subsequent stimulation with 15 mM glucose. Sodium pyruvate
      did not sensitize islets. These findings support the concept that the
      mitochondrial metabolism of nutrient molecules is an event sufficient to acutely
      augment insulin release from the beta cell, to increase phospholipase C-mediated
      phosphoinositide hydrolysis, and to induce time-dependent potentiation of insulin
      secretion.

PMID- 9013601
TI  - An alanine residue in the M3-M4 linker lines the glycine binding pocket of the N
      methyl-D-aspartate receptor.
AB  - While attempting to map a central region in the M3-M4 linker of the N-methyl-D
      aspartate receptor NR1 subunit, we found that mutation of a single position, Ala
      714, greatly reduced the apparent affinity for glycine. Proximal N-glycosylation
      localized this region to the extracellular space. Glycine affinities of
      additional Ala-714 mutations correlated with side chain volume. Substitution of
      alanine 714 with cysteine did not alter glycine sensitivity, although this mutant
      was rapidly inhibited by dithionitrobenzoate. Glycine protected the A714C mutant
      from modification by dithionitrobenzoate, whereas the co-agonist L-glutamate was
      ineffective. These experiments place Ala-714 in the glycine binding pocket of the
      N-methyl-D-aspartate receptor, a determination not predicted by previous
      structural models based on bacterial periplasmic binding protein homology.

PMID- 9013602
TI  - Bipolar functional expression of transcobalamin II receptor in human intestinal
      epithelial Caco-2 cells.
AB  - Transcobalamin II (TC II) receptor is expressed in the apical and basolateral
      membranes of human intestinal mucosa and in post-confluent human intestinal
      epithelial Caco-2 cells with a 6-7-fold enrichment in basolateral membranes. Caco
      2 cells grown on culture inserts bound (at 5 degrees C) 30 and 180 fmol of the
      ligand, TC II-[57Co]cobalamin (Cbl), to the apical and the basolateral surfaces,
      respectively. Within 5 h at 37 degrees C, all apically bound Cbl was internalized
      and subsequently transcytosed as TC II-Cbl. In contrast, all basolateral surface
      bound Cbl was internalized and retained by the cells, but transferred from TC II
      to other cellular proteins. Chloroquine or leupeptin had no effect on the apical
      to basolateral transcytosis of either [57Co]Cbl or 125I-TC II. In contrast,
      following basolateral internalization of the ligand, both chloroquine and
      leupeptin inhibited the intracellular degradation of 125I-TC II, which resulted
      in secretion of 60-65% of TC II-Cbl complex into the basolateral medium. When
      125I-TC II-Cbl was orally administered to rats, intact labeled TC II was detected
      in the portal blood 4 and 8 h later. These studies suggest that TC II-Cbl is
      processed when presented to the (a) apical/luminal side by a hitherto
      unrecognized non-lysosomal pathway in which both TC II and Cbl are transcytosed
      and (b) basolateral side by the lysosomal pathway in which TC II is degraded and
      the released Cbl is utilized.

PMID- 9013603
TI  - Phosphorylation of protein kinase C-alpha on serine 657 controls the accumulation
      of active enzyme and contributes to its phosphatase-resistant state.
AB  - Serine 657 in protein kinase C-alpha (PKCalpha) is a site of phosphorylation on
      expression of the recombinant protein in mammalian cells. To define the function
      of this phosphorylation, PKCalpha species with mutations of this site were
      investigated. The alanine mutant, S657A PKCalpha, displayed slow phosphate
      accumulation in pulse-chase experiments, indicating a rate-limiting role in the
      initial phase of phosphorylation. Consistent with this, the aspartic acid mutant,
      S657D PKCalpha, showed an increased rate of phosphate accumulation. Both the
      S657D and S657A PKCalpha mutants were slow to accumulate as fully phosphorylated
      forms during a second phase of phosphorylation. This latter property is shown to
      correlate with an increased phosphatase sensitivity and decreased protein kinase
      activity for these two PKCalpha mutants. It is further shown that once fully
      phosphorylated, the S657D PKCalpha mutant displays WT PKCalpha properties with
      respect to thermal stability and phosphatase sensitivity in vitro and in vivo; in
      contrast, the S657A PKCalpha mutant remains sensitive. The properties of the Ser
      657 site PKCalpha mutants define functional roles for this phosphorylation in
      both the accumulation of phosphate on PKCalpha as well as in its agonist-induced
      dephosphorylation. These results are discussed in the context of a working model
      of PKCalpha behavior, providing insight into the workings of other kinases with
      equivalent sites of phosphorylation.

PMID- 9013604
TI  - Inhibition of p75 tumor necrosis factor receptor by antisense oligonucleotides
      increases hypoxic injury and beta-amyloid toxicity in human neuronal cell line.
AB  - Recent evidence indicates that tumor necrosis factor-alpha (TNF-alpha) is up
      regulated following brain injury and in neurodegenerative disorders such as
      stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease. TNF
      alpha elicits its biological effects through two distinct TNF receptor (TNFR)
      subtypes: p55 TNFR (TNFR1) and p75 TNFR (TNFR2). Studies have demonstrated that
      the p55 TNFR contributes to cell death, whereas the role of the p75 TNFR in
      neuronal viability is unclear. To better understand the role of p75 TNFR, we
      treated human neuronal SH-SY5Y cells with phosphorothioate-modified antisense
      oligonucleotides (ASO) for p75 TNFR and established that ASO inhibited p75 TNFR
      expression. Treatment of SH-SY5Y cells with ASO alone did not affect cell
      viability, whereas treatment with both ASO and human TNF-alpha significantly
      increased cell death relative to treatment with TNF-alpha alone. Moreover,
      addition of ASO significantly increased the level of cell injury observed
      following hypoxic conditions or exposure of beta-amyloid peptide. These results
      indicate that inhibition of p75 TNFR using ASO increases the vulnerability of
      neurotypic cells to insults and suggest that the p75 TNFR may not be required for
      normal neuronal cell viability but rather plays a protective role following
      injury.

PMID- 9013606
TI  - Molecular structures involved in L-type calcium channel inactivation. Role of the
      carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in the
      kinetics and Ca2+ dependence of inactivation.
AB  - The pore-forming alpha1C subunit is the principal component of the voltage
      sensitive L-type Ca2+ channel. It has a long cytoplasmic carboxyl-terminal tail
      playing a critical role in channel gating. The expression of alpha1C subunits is
      characterized by alternative splicing, which generates its multiple isoforms.
      cDNA cloning points to a diversity of human hippocampus alpha1C transcripts in
      the region of exons 40-43 that encode a part of the 662-amino acid carboxyl
      terminus. We compared electrophysiological properties of the well defined 2138
      amino acid alpha1C,77 channel isoform with two splice variants, alpha1C,72 and
      alpha1C,86. They contain alterations in the carboxyl terminus due to alternative
      splicing of exons 40-42. The 2157-amino acid alpha1C,72 isoform contains an
      insertion of 19 amino acids at position 1575. The 2139-amino acid alpha1C,86 has
      80 amino acids replaced in positions 1572-1651 of alpha1C,77 by a non-identical
      sequence of 81 amino acids. When expressed in Xenopus oocytes, all three splice
      variants retained high sensitivity toward dihydropyridine blockers but showed
      large differences in gating properties. Unlike alpha1C,77 and alpha1C,72, Ba2+
      currents (IBa) through alpha1C,86 inactivated 8-10 times faster at +20 mV, and
      its inactivation rate was strongly voltage-dependent. Compared to alpha1C,77, the
      inactivation curves of IBa through alpha1C,86 and alpha1C,72 channels were
      shifted toward more negative voltages by 11 and 6 mV, respectively. Unlike
      alpha1C,77 and alpha1C,72, the alpha1C,86 channel lacks a Ca2+-dependent
      component of inactivation. Thus the segment 1572-1651 of the cytoplasmic tail of
      alpha1C is critical for the kinetics as well as for the Ca2+ and voltage
      dependence of L-type Ca2+ channel gating.

PMID- 9013605
TI  - Tyrosine kinase receptors concentrated in caveolae-like domains from neuronal
      plasma membrane.
AB  - Recent evidence suggests that tyrosine kinases are highly organized in caveolae
      of tissue culture cells. We now report the isolation of a membrane domain from
      neuronal plasma membranes that has the biochemical characteristics of caveolae. A
      low density membrane (LDM) fraction with the same density as caveolae was highly
      enriched in tyrosine kinases such as insulin receptors, neurotrophin receptors,
      Eph family receptors, and Fyn. Grb2, Ras, heterotrimeric GTP-binding proteins,
      and Erk2 were also concentrated in the LDM. Incubation of the LDM fraction at 37
      degrees C stimulated the phosphorylation on tyrosine of multiple, resident
      proteins, whereas the bulk membrane fraction was devoid of tyrosine kinase
      activity. The LDM, which makes up approximately 5-10% of the plasma membrane
      protein, appears to be organized for signal transduction.

PMID- 9013607
TI  - Tissue-specific and developmental regulation of the rat insulin II gene enhancer,
      RIPE3, in transgenic mice.
AB  - The rat insulin II gene enhancer, RIPE3 (-126 to -86), mediates beta-islet cell
      specific activity in transfection assays. To investigate the in vivo activity of
      RIPE3, we generated mice carrying a transgene consisting of three copies of RIPE3
      linked to a minimal chicken ovalbumin promoter in conjunction with sequences
      encoding the human growth hormone gene. 13 transgenic mice were obtained, 11 of
      which expressed the transgene, as determined by serum radioimmunoassay for human
      growth hormone. Expression of the transgene was assessed for cell specificity by
      immunocytochemistry. The pancreatic islet cells invariably stained for growth
      hormone, while the acinar and ductal cells did not. Staining of adjacent sections
      for insulin, glucagon, and somatostatin revealed that growth hormone was
      expressed in the beta-cell in all of the mice analyzed, but in some mice alpha
      cells also contained growth hormone. RNase protection analysis revealed that the
      tissues that consistently express the transgene in these animals are the pancreas
      and brain. Developmental analysis revealed that the transgene was expressed in
      the pancreatic bud at embryonic day 9.5, corresponding to the temporal expression
      pattern of the insulin gene. These results signify that an element as small as 41
      base pairs is capable of regulating pancreatic temporal and spatial gene
      expression in vivo.

PMID- 9013608
TI  - Structural aspects of interfacial adsorption. A crystallographic and site
      directed mutagenesis study of the phospholipase A2 from the venom of Agkistrodon
      piscivorus piscivorus.
AB  - Recent genetic and structural studies have shed considerable light on the
      mechanism by which secretory phospholipases A2 interact with substrate
      aggregates. Electrostatic forces play an essential role in optimizing interfacial
      catalysis. Efficient and productive adsorption of the Class I bovine pancreatic
      phospholipase A2 to anionic interfaces is dependent upon the presence of two
      nonconserved lysine residues at sequence positions 56 and 116, implying that
      critical components of the adsorption surface differ among enzyme species (Dua,
      R., Wu, S.-K., and Cho, W. (1995) J. Biol. Chem. 270, 263-268). In an effort to
      further characterize the protein residues involved in interfacial catalysis, we
      have determined the high resolution (1.7 A) x-ray structure of the Class II Asp
      49 phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus.
      Correlation of the three-dimensional coordinates with kinetic data derived from
      site-directed mutations near the amino terminus (E6R, K7E, K10E, K11E, and K16E)
      and the active site (K54E and K69Y) defines much of the interface topography.
      Lysine residues at sequence positions 7 and 10 mediate the adsorption of A. p.
      piscivorus phospholipase A2 to anionic interfaces but play little role in the
      enzyme's interaction with electrically neutral surfaces or in substrate binding.
      Compared to the native enzyme, the mutant proteins K7E and K10E demonstrate
      comparable (20-fold) decreases in affinity and catalysis on polymerized mixed
      liposomes of 1-hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine and
      1,2-bis[12-(lipoyloxy)dodecanoyl]-sn-glycero-3-phosphoglycerol, while the double
      mutant, K7E/K10E, shows a more dramatic 500-fold decrease in catalysis and
      interfacial adsorption. The calculated contributions of Lys-7 and Lys-10 to the
      free energy of binding of A. p. piscivorus phospholipase A2 to anionic liposomes
      (-1.8 kcal/mol at 25 degrees C per lysine) are additive (i.e. -3.7 kcal/mol) and
      together represent nearly half of the total binding energy. Although both lysine
      side chains lie exposed at the edge of the proposed interfacial adsorption
      surface, they are geographically remote from the corresponding interfacial
      determinants for the bovine enzyme. Our results confirm that interfacial
      adsorption is largely driven by electrostatic forces and demonstrate that the
      arrangement of the critical charges (e.g. lysines) is species-specific. This
      variability in the topography of the adsorption surface suggests a corresponding
      flexibility in the orientation of the active enzyme at the substrate interface.

PMID- 9013609
TI  - Species-specific regulation and switching of transcription between stage-specific
      ribosomal RNA genes in Plasmodium berghei.
AB  - Malaria parasites (Plasmodium spp.) differentially express structurally distinct
      sets of rRNA genes in a stage-specific manner. The four rRNA genes of the rodent
      malaria parasite, P. berghei, form two classes of 2 units that are genetically
      unlinked and termed A-type and S-type. Through Northern analysis and in situ
      hybridization, expression of the units was demonstrated in synchronized parasite
      preparations covering the developmental pathway from the initiation of the blood
      stage asexual cycle to the production of mature ookinetes. A-type units were
      transcribed in direct response to cell growth in bloodstage asexual parasites yet
      were differentially regulated during male (inactive) and female (active)
      gametocytogenesis. S-type expression was not confined solely to the mosquito
      stages and exhibited a finite period of expression in a subset of bloodstage
      trophozoites that was significantly elevated in gametocyte-producing parasites.
      Unlike in the human parasite, P. falciparum, there was no evidence for
      accumulation of precursor forms of the S-type transcripts in gametocytes. No
      significant rRNA transcription was observed in cultured, fertilized ookinetes
      until approximately 20 h of development when S-type transcription was initiated.
      The results further demonstrate that in Plasmodium the expression of the
      different rRNA units is linked to developmental progression but in a species
      specific manner.

PMID- 9013610
TI  - Phosphorylation, subcellular localization, and membrane orientation of the
      Alzheimer's disease-associated presenilins.
AB  - Presenilins 1 and 2 are unglycosylated proteins with apparent molecular mass of
      45 and 50 kDa, respectively, in transfected COS-1 and Chinese hamster ovary
      cells. They colocalize with proteins from the endoplasmic reticulum and the Golgi
      apparatus in transfected and untransfected cells. In COS-1 cells low amounts of
      intact endogeneous presenilin 1 migrating at 45 kDa are detected together with
      relative larger amounts of presenilin 1 fragments migrating between 18 and 30
      kDa. The presenilins have a strong tendency to form aggregates (mass of 100-250
      kDa) in SDS-polyacrylamide gel electrophoresis, which can be partially resolved
      when denatured by SDS at 37 degrees C instead of 95 degrees C. Sulfation,
      glycosaminoglycan modification, or acylation of the presenilins was not observed,
      but both proteins are posttranslationally phosphorylated on serine residues. The
      mutations Ala-246 --> Glu or Cys-410 --> Tyr that cause Alzheimer's disease do
      not interfere with the biosynthesis or phosphorylation of presenilin 1. Finally,
      using low concentrations of digitonin to selectively permeabilize the cell
      membrane but not the endoplasmic reticulum membrane, it is demonstrated that the
      two major hydrophilic domains of presenilin 1 are oriented to the cytoplasm. The
      current investigation documents the posttranslational modifications and
      subcellular localization of the presenilins and indicates that postulated
      interactions with amyloid precursor protein metabolism should occur in the early
      compartments of the biosynthetic pathway.

PMID- 9013611
TI  - Molecular identification of a novel candidate sorting receptor purified from
      human brain by receptor-associated protein affinity chromatography.
AB  - Receptor-associated protein (RAP) is an endoplasmic reticulum/Golgi protein
      involved in the processing of receptors of the low density lipoprotein receptor
      family. A approximately 95-kDa membrane glycoprotein, designated gp95/sortilin,
      was purified from human brain extracts by RAP affinity chromatography and cloned
      in a human cDNA library. The gene maps to chromosome 1p and encodes an 833-amino
      acid type I receptor containing an N-terminal furin cleavage site immediately
      preceding the N terminus determined in the purified protein. Gp95/sortilin is
      expressed in several tissues including brain, spinal cord, and testis.
      Gp95/sortilin is not related to the low density lipoprotein receptor family but
      shows intriguing homologies to established sorting receptors: a 140-amino acid
      lumenal segment of sortilin representing a hitherto unrecognized type of
      extracellular module shows extensive homology to corresponding segments in each
      of the two lumenal domains of yeast Vps10p, and the extreme C terminus of the
      cytoplasmic tail of sortilin contains the casein kinase phosphorylation consensus
      site and an adjacent dileucine sorting motif that mediate assembly protein-1
      binding and lysosomal sorting of the mannose-6-phosphate receptors. Expression of
      a chimeric receptor containing the cytoplasmic tail of gp95/sortilin demonstrates
      evidence that the tail conveys colocalization with the cation-independent
      mannose6-phosphate receptor in endosomes and the Golgi compartment.

PMID- 9013612
TI  - Molecular characterization of p62, a mitotic apparatus protein required for
      mitotic progression.
AB  - A 62-kDa (p62) mitotic apparatus-associated protein is important for the proper
      progression of mitosis in sea urchin embryos (Dinsmore, J. H., and Sloboda, R. D.
      (1989) Cell 53, 769-780). We have isolated and characterized a full-length p62
      cDNA of 3374 base pairs which encodes an extremely acidic polypeptide of 411
      amino acids having a calculated Mr of 46,388 and a pI of 4.01; p62 is a unique
      protein with no significant identity to any known proteins. Southern and Northern
      blot analyses demonstrate that the gene for p62 is present once in the sea urchin
      genome and the corresponding mRNA is present in unfertilized eggs and in early
      embryos through and up to the gastrula stage. Sequence analysis suggests certain
      regions may participate in chromatin association and microtubule binding, an
      observation that is consistent with previous immunological data (Ye, X., and
      Sloboda, R. D. (1995) Cell Motil. Cytoskeleton 30, 310-323) as well as data
      reported herein. Confocal microscopy reveals that during interphase the protein
      binds to chromatin in the nuclei of sea urchin eggs. In the germinal vesicles of
      clam oocytes at prophase of meiosis I, p62 binds to the condensed chromosomes.
      Currently, truncated clones of p62 are being used to identify the tubulin and
      chromatin binding domains.

PMID- 9013613
TI  - Expression of human pICln and ClC-6 in Xenopus oocytes induces an identical
      endogenous chloride conductance.
AB  - pICln is a protein that induces an outwardly rectifying, nucleotide-sensitive
      chloride current (ICln) when expressed in Xenopus oocytes, but its precise
      function (plasma-membrane anion channel versus cytosolic regulator of a channel)
      remains controversial. We now report that a chloride current identical to ICln is
      induced when Xenopus oocytes are injected with human ClC-6 RNA. Indeed, both the
      pICln and the ClC-6 induced current are outwardly rectifying, they inactivate
      slowly at positive potentials and have an anion permeability sequence NO3- > I- >
      Br- > Cl- > gluconate. Cyclamate, NPPB, and extracellular cAMP block the induced
      currents. The success rate of current expression is significantly increased when
      the injected Xenopus oocytes are incubated at a higher temperature (24 or 37
      degrees C) prior to the analysis. In addition, the ICln current was detected in
      6.2% of noninjected control Xenopus oocytes. We therefore conclude that the ICln
      current in Xenopus oocytes corresponds to an endogenous conductance that can be
      activated by expression of structurally unrelated proteins. Furthermore,
      functional, biochemical, and morphological observations did not support the
      notion that pICln resides in the plasma membrane either permanently or
      transiently after cell swelling. Thus, it is unlikely that pICln forms the
      channel that is responsible for the ICln current in Xenopus oocytes.

PMID- 9013614
TI  - Molecular genetic analysis of a human neuropeptide Y receptor. The human homolog
      of the murine "Y5" receptor may be a pseudogene.
AB  - Neuropeptide Y is a 36-amino-acid peptide amide with numerous biological
      activities. These functions are mediated through several pharmacologically
      distinct receptors. To date five receptor subtypes have been cloned. Here we
      report the isolation, by low stringency homology cloning from a hypothalamic
      library, of a cDNA encoding the human homolog of the murine neuropeptide Y
      receptor subsequently reported (). Translation of the human Y1-like receptor
      clone suggested that it encoded a receptor which is truncated in the third
      extracellular loop. Comparison of the human Y1-like sequence to that of the human
      Y1 receptor suggested that the truncated receptor could have resulted from a
      frameshift due to a single nucleotide deletion in the sixth transmembrane domain.
      Southern blot analysis suggested that the gene is single copy in the human
      genome. The gene is located on chromosome 5q. To test the hypothesis that allelic
      variation of nucleic acid length within the sixth transmembrane domain of the Y1
      like receptor may exist to produce a functional receptor, genomic DNA from 192
      individuals of various ages, ethnic backgrounds, and degrees of obesity were
      analyzed electrophoretically and by direct sequencing. No variation was detected
      in any of the subjects, indicating that this receptor subtype may be a
      transcribed pseudogene in humans.

PMID- 9013615
TI  - Human methionine synthase. cDNA cloning, gene localization, and expression.
AB  - Human cDNAs for methionine synthase (5-methyltetrahydrofolate:L-homocysteine S
      transmethylase; EC 2.1.1. 13) have been isolated from fetal and adult liver and
      HepG2 libraries. The cDNAs span 7.2 kilobases (kb) and consist of a 394-base pair
      upstream untranslated region, a 3795-base pair open reading frame encoding a 1265
      residue 140.3-kDa protein, and about 3 kb of 3' region. The deduced protein
      sequence shares 53 and 63% identity with the Escherichia coli and the presumptive
      Caenorhabditis elegans proteins, respectively, and contains all residues
      implicated in B12 binding to the E. coli protein. Several potential polymorphisms
      and a cryptic splice deletion were detected in the coding region of the cDNAs. A
      polymorphism that results in a D919G modification in the protein is fairly common
      in human DNA samples. Northern analyses of poly(A) mRNA indicated two major
      species of about 8 and 10 kb in human tissues and some minor, partially spliced
      species. mRNA levels were highest in the pancreas, skeletal muscle, and heart of
      the adult and in the kidney in the fetus and were low in adult liver. Genomic
      clones were isolated and the 5' region was analyzed. Exon 1 is preceded by a
      number of potential promoter sites, including an E box, CAAT boxes, and a GC box,
      but this region lacks a TATA element. The human methionine synthase gene was
      localized to chromosome region 1q42.3-43 by in situ hybridization.

PMID- 9013616
TI  - H1-mediated repression of transcription factor binding to a stably positioned
      nucleosome.
AB  - Previously, we reported that histone H1 binding to nucleosome cores results in
      the repression of binding of the basic helix-loop-helix upstream stimulatory
      factor (USF) (Juan, L.-J., Utley, R. T., Adams, C. C., Vettese-Dadey, M., and
      Workman, J. L. (1994) EMBO J. 13, 6031-6040). We have tested whether this
      inhibition resulted from H1-mediated changes in nucleosome positioning (Ura, K.,
      Hayes, J. J., and Wolffe, A. P. (1995) EMBO J. 14, 3752-3765) forcing the USF
      recognition sequence into less accessible locations within the nucleosome.
      Nucleosome boundaries were determined by assays combining micrococcal nuclease
      and restriction endonuclease digestion. A unique pair of boundaries were
      observed, indicating a single nucleosome translational position. This nucleosome
      position did not change on H1 or USF binding. Thus, H1 repression of USF binding
      was independent of nucleosome mobility, indicating an alternative mechanism of H1
      repression. H1 repressed USF binding at a site 35 base pairs into the nucleosome
      core more effectively than at a site near the "linker" DNA, suggesting that
      inhibition by H1 was not simply due to steric occlusion. Instead, these data are
      consistent with a model by which H1 binding reduces transient dynamic exposure of
      the DNA from the histone octamer surface (Polach, K. L., and Widom, J. (1995) J.
      Mol. Biol. 254, 130-149).

PMID- 9013617
TI  - Selective modulation of the major histocompatibility complex class II antigen
      presentation pathway following B cell receptor ligation and protein kinase C
      activation.
AB  - We noticed that B cell receptor ligation or phorbol 12-myristate 13-acetate
      treatment induced intracellular vesicles containing major histocompatibility
      complex (MHC) class II and invariant chain (Ii), and increased the amount of
      transmembrane p12 Ii fragments coimmunoprecipitated with class II molecules. To
      determine the influence of protein kinase C activation on the MHC class II
      presentation pathway, we analyzed the subcellular distribution of Ii, the
      induction of SDS-stable forms of class II molecules, and their ability to present
      different antigens. Ii chains visualized with luminal and cytoplasmic directed
      antibodies appeared in early endosomal compartments accessible to transferrin in
      response to phorbol 12-myristate 13-acetate treatment, whereas transmembrane Ii
      degradation products equivalent to the p12 Ii fragments were colocalized with the
      B cell receptors internalized after cross-linking. Protein kinase C activation
      delayed in parallel the formation of SDS-stable forms of class II molecules and
      reduced the presentation of antigenic determinants requiring newly synthesized
      class II alphabeta-Ii complexes. These data indicate that B cell activation
      affects Ii processing and MHC class II peptide loading in endosomal compartments
      intersecting the biosynthetic pathway.

PMID- 9013618
TI  - F1-ATPase, roles of three catalytic site residues.
AB  - Three critical residues, beta-Lys-155, beta-Asp-242, and beta-Glu-181, situated
      close to the gamma-phosphate of MgATP in F1-ATPase catalytic sites, were
      investigated. The mutations betaK155Q, betaD242N, and betaE181Q were each
      combined with the betaY331W mutation; the fluorescence signal of beta-Trp-331 was
      used to determine MgATP, MgADP, ATP, and ADP binding parameters for the three
      catalytic sites of the enzyme. The quantitative contribution of side chains to
      binding energy at all three catalytic sites was calculated. The following
      conclusions were made. The major functional interaction of beta-Lys-155 is with
      the gamma-phosphate of MgATP and is of primary importance at site 1 (the site of
      highest affinity) and site 2. Release of MgATP during oxidative phosphorylation
      requires conformational re-positioning of this residue. The major functional
      interaction of beta-Asp-242 is with the magnesium of the magnesium nucleotide at
      site 1; it has little or no influence at site 2 or 3. In steady-state turnover,
      the MgATP hydrolysis reaction occurs at site 1. beta-Glu-181 contributes little
      to nucleotide binding; its major catalytic effect derives apparently from a role
      in reaction chemistry per se. This work also emphasizes that nucleotide binding
      cooperativity shown by the three catalytic sites toward MgATP and MgADP is
      absolutely dependent on the presence of magnesium.

PMID- 9013619
TI  - Prostacyclin synthase active sites. Identification by molecular modeling-guided
      site-directed mutagenesis.
AB  - Prostacyclin synthase (PGIS), a cytochrome P450 enzyme, catalyzes the
      biosynthesis of a physiologically important molecule, prostacyclin. In this study
      we have used a molecular modeling-guided site-directed mutagenesis to predict the
      active sites in substrate binding pocket and heme environment of PGIS. A three
      dimensional model of PGIS was constructed using P450BM-3 crystal structure as the
      template. Our results indicate that residues Ile67, Val76, Leu384, Pro355,
      Glu360, and Asp364, which were suggested to be located at one side of lining of
      the substrate binding pocket, are essential for catalytic activity. This region
      containing beta1-1, beta1-2, beta1-3, and beta1-4 strands is predicted well by
      the model. At the heme region, Cys441 was confirmed to be the proximal axial
      ligand of heme iron. The conserved Phe and Arg in P450BM-3 were substituted by
      Leu112 and Asp439, respectively in PGIS. Alteration of Leu112 to Phe retained the
      activity, indicating that Leu112 is a functional substitution for Phe. In
      contrast, mutant Asp439 --> Ala exhibited a slight increase in activity. This
      result implies a difference in the heme region between P450BM-3 and PGIS. Our
      results also indicate that stability of PGIS expression is not affected by heme
      site or active site mutations.

PMID- 9013620
TI  - An evolutionarily conserved domain in a subfamily of Rabs is crucial for the
      interaction with the guanyl nucleotide exchange factor Mss4.
AB  - Mss4 is a guanine nucleotide exchange factor that specifically binds to, and
      promotes GDP-GTP exchange on, a subset of the Rab GTPases (Burton, J. L., Burns,
      M. E., Gatti, E., Augustine, G. J., and De Camilli, P. (1994) EMBO J. 13, 5547
      5558). In order to identify the domain(s) of the GTPase that is important for
      this interaction, protein chimeras were constructed between Rab3a, which binds
      Mss4, and Rab5a, which does not bind Mss4. We have identified the amino-terminal
      portion of Rab3a as the Mss4-binding region, with the effector domain being
      critically required for binding and the flanking regions further enhancing the
      interaction. Sequence comparisons have revealed that Mss4-binding Rabs share more
      homology with each other than with Rabs that do not bind Mss4. The region of
      highest homology between these Rabs, which defines them as members of the same
      evolutionary branch within the Rab subfamily, coincides with the domain shown
      here to be critical for Mss4 binding. A mutation in the zinc-binding domain of
      Mss4 (Mss4 D96H), a region that is highly conserved between Mss4 and its yeast
      homologue Dss4, completely abolished its property to bind to, and promote GDP-GTP
      exchange on, Rab3a. Thus, the preservation of the Mss4/Dss4-GTPase interaction
      appears to have been a critical factor in the evolution of this subset of Rab
      proteins.

PMID- 9013621
TI  - Proteolytic processing of sulfated secretogranin II in the trans-Golgi network of
      GH3B6 prolactin cells.
AB  - Secretogranin II (SgII) is a protein specific to the matrix of the secretory
      granules in neurons and neuroendocrine cells. We have already demonstrated the
      precursor-product relationship between sulfated SgII and four N-terminal derived
      peptides in GH3B6 prolactin cells. In this study, we have investigated the
      subcellular compartment in which the cleavage of SgII is initiated by taking
      advantage of its tyrosine sulfation in the trans-Golgi network (TGN). In order to
      prevent export of radiosulfated SgII from the TGN, we used brefeldin A (BFA) as
      well as incubation at 20 degrees C. BFA completely inhibited the cleavage of SgII
      when added immediately post-pulse. BFA added a few minutes post-pulse or after a
      20 degrees C incubation, however, permitted the cleavage of SgII in the presence
      of the drug. These SgII-derived peptides generated in the presence of BFA could
      not be released upon stimulation of the cells by either thyroliberin, a
      physiological secretagogue, or KCl. These results demonstrate that SgII can be
      cleaved in the TGN. They also evidence that the cleavage occurs in a distal
      compartment of the TGN different from the sulfation site. The transfer of SgII
      from the sulfation site to this distal compartment of the TGN involves BFA
      sensitive membrane dynamics.

PMID- 9013622
TI  - Expression of the 90K immunostimulator gene is controlled by a promoter with
      unique features.
AB  - 90K is a secreted glycoprotein with tumor suppressive functions, which is up
      regulated in various types of cancer and in AIDS. In order to understand the
      regulation of its expression, the mouse 90K gene was isolated and analyzed. The
      gene spans about 8.8-kilobase pairs and consists of 6 exons and was localized on
      chromosome 11, region E. RNase protection identified one major transcription
      start site (+1) and three minor ones (-3, +32, +34). The mouse 90K gene was found
      to have a TATA-less promoter of unusual structure. The 2. 3-kilobase pair 5'
      flanking region exhibited strong promoter activity in NIH 3T3 cells; however, it
      contained neither a TATA-box nor a SP1 site and was not GC-rich. No known
      initiator motif was found around the transcription start site. 5'- and 3'
      deletions defined a minimal promoter of 51 base pairs (-66 --> -16), not
      including the start site, essential and sufficient for promoter activity. This
      minimal promoter showed increased activity after stimulation with interferon
      gamma or poly(I.C), a substance mimicking viral infection. Essential for both
      inductions was the integrity of an interferon regulatory factor element within
      this sequence, a potential binding site for the anti-oncogenic transcription
      factor interferon regulatory factor-1.

PMID- 9013623
TI  - Interactions of the subunits of smooth muscle myosin phosphatase.
AB  - Myosin phosphatase from smooth muscle consists of a catalytic subunit (PP1c) and
      two non-catalytic subunits, M130 and M20. Interactions among PP1c, M20, and
      various mutants of M130 were investigated. Using the yeast two-hybrid system,
      PP1c was shown to bind to the NH2-terminal sequence of M130, 1-511. Other
      interactions were detected, i.e. PP1c to PP1c, M20 to the COOH-terminal fragment
      of M130, and dimerization of the COOH-terminal fragment of M130. Mutants of M130
      were constructed to localize the PP1c and light chain binding regions. Results
      from the two-hybrid system indicated two binding sites for PP1c on M130: one site
      in the NH2-terminal 38 residues and a weaker site(s) in the ankyrin repeats
      region. Inhibition of PP1c activity with phosphorylase a by the M130 mutants also
      was consistent with the assignment of these two sites. Overlay assays showed
      binding of phosphorylated light chain to the ankyrin repeats, probably in the
      COOH-terminal repeats. Activation of PP1c with phosphorylated light chain
      required binding sites for PP1c and substrate, plus an additional sequence COOH
      terminal to the ankyrin repeats. Thus, activation of phosphatase and binding of
      PP1c and substrate are properties of the NH2-terminal one-third of M130.

PMID- 9013624
TI  - Coinduction of nitric-oxide synthase and arginase I in cultured rat peritoneal
      macrophages and rat tissues in vivo by lipopolysaccharide.
AB  - Nitric oxide is synthesized by nitric-oxide synthase from arginine, a common
      substrate of arginase. Rat peritoneal macrophages were cultured in the presence
      of bacterial lipopolysaccharide (LPS), and expression of the inducible isoform of
      nitric-oxide synthase (iNOS) and liver-type arginase (arginase I) was analyzed.
      mRNAs for iNOS and arginase I were induced by LPS in a dose-dependent manner.
      iNOS mRNA appeared 2 h after LPS treatment and increased to a near maximum at 8
      12 h. On the other hand, arginase I mRNA that was undetectable prior to the
      treatment began to increase after 4 h with a lag time and reached a maximum at 12
      h. Immunoblot analysis showed that iNOS and arginase I proteins were also
      induced. mRNA for arginase II, an arginase isozyme, was not detected in the LPS
      activated peritoneal cells. mRNA for CCAAT/enhancer-binding protein beta
      (C/EBPbeta), a transactivator of the arginase I gene, was also induced, and the
      induction was more rapid than that of arginase I mRNA. Changes in iNOS and
      arginase I mRNAs were also examined in LPS-injected rats in vivo. iNOS mRNA
      increased rapidly in the lung and spleen, reached a maximum 2-6 h after the LPS
      treatment, and decreased thereafter. Arginase I mRNA was induced markedly and
      more slowly in both tissues, reaching a maximum in 12 h. Thus, arginase I appears
      to have an important role in down-regulating nitric oxide synthesis in murine
      macrophages by decreasing the availability of arginine, and the induction of
      arginase I is mediated by C/EBPbeta.

PMID- 9013626
TI  - Oleosin of plant seed oil bodies is correctly targeted to the lipid bodies in
      transformed yeast.
AB  - Yeast (Saccharomyces cerevisiae) has been used extensively as a heterologous
      eukaryotic system to study the intracellular targeting of proteins to different
      organelles. The lipid bodies in yeast have not been previously subjected to such
      studies. These organelles are functionally equivalent to the subcellular storage
      oil bodies in plant seeds. A plant oil body has a matrix of oils
      (triacylglycerols) surrounded by a layer of phospholipids embedded with abundant
      structural proteins called oleosins. We tested whether plant oleosin could be
      correctly targeted to the lipid bodies in transformed yeast. The coding region of
      a maize (Zea mays L.) oleosin gene was incorporated into yeast high copy and low
      copy number plasmids in which its expression was under the control of GAL1
      promoter. Yeast strains transformed with these plasmids produced oleosin when
      grown in a medium containing galactose but not glucose. The oleosin produced in
      yeast had a molecular mass slightly higher than that of the native protein in
      maize. Oleosin accumulated concomitantly with the storage lipids during growth of
      the transformed yeast, and it was not secreted. Subcellular fractionation of the
      cell extracts obtained by two different cell breakage procedures revealed that
      the oleosin was largely restricted to the lipid bodies. Oleosin apparently did
      not affect the lipid contents and composition of the transformed yeast lipid
      bodies but replaced some of the native proteins associated with the organelles.
      Immunocytochemistry of the transformed yeast cells showed that the oleosin was
      present mostly on the periphery of the lipid bodies. Oleosin isolated from maize
      or transformed yeast strain, alone or in the presence of phospholipids or SDS,
      did not bind to the yeast lipid bodies in vitro. We conclude that plant oleosin
      is correctly targeted to the lipid bodies in transformed yeast and that yeast may
      be used as a heterologous system to dissect the intracellular targeting signals
      in the oleosin.

PMID- 9013625
TI  - The glucocorticoid-responsive gene cascade. Activation of the rat arginase gene
      through induction of C/EBPbeta.
AB  - The gene for liver-type arginase, an ornithine cycle enzyme, is induced by
      glucocorticoids in a delayed secondary manner. An enhancer element located around
      intron 7 of the rat arginase gene shows delayed glucocorticoid responsiveness,
      and it harbors two sites binding with members of the CCAAT/enhancer binding
      protein (C/EBP) family. Here, we investigate the role of these C/EBP binding
      sites in glucocorticoid response of the arginase gene. When inserted in front of
      the herpes simplex virus thymidine kinase promoter, these C/EBP sites exhibited
      glucocorticoid responsiveness in reporter transfection assay using rat hepatoma
      H4IIE cells. In footprint analysis using nuclear extracts of H4IIE cells,
      profiles of the protected areas of the two C/EBP sites changed when cells were
      treated with dexamethasone. In gel shift analysis, the complex formation for the
      two C/EBP sites was augmented in response to dexamethasone. Antibody
      supershift/inhibition analysis demonstrated that a major portion of the binding
      proteins induced by dexamethasone is C/EBPbeta. Induction of arginase mRNA by
      dexamethasone was preceded by augmentation of the C/EBP site-binding activities,
      which followed increase in C/EBPbeta mRNA. These results were consistent with the
      notion that the glucocorticoid response of the arginase gene is mediated by
      C/EBPbeta.

PMID- 9013627
TI  - Induction of cyclooxygenase-2 expression by peroxisome proliferators and non
      tetradecanoylphorbol 12,13-myristate-type tumor promoters in immortalized mouse
      liver cells.
AB  - Increased expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in
      prostaglandin synthesis, has been associated with growth regulation and
      carcinogenesis in several systems. COX-2 is known to be induced by cytokines and
      the skin tumor promoter 12-tetradecanoylphorbol-13-myristate (TPA). In the
      present study, we investigated the effects of several non-TPA-type tumor
      promoters on COX-2 expression in immortalized mouse liver cells. Specifically, we
      tested peroxisome proliferators (PPs), which are rodent liver tumor promoters
      that cause gross alterations in cellular lipid metabolism, the rodent liver tumor
      promoter phenobarbital, and the skin tumor promoters okadaic acid and
      thapsigargin. The PPs Wy-14643, mono-ethylhexyl phthalate, clofibrate,
      ciprofibrate ethyl ester, and eicosatetraynoic acid each caused large increases
      in COX-2 mRNA and protein, with maximal expression seen approximately 10 h after
      treatment of quiescent cells. COX-2 expression was also induced by thapsigargin,
      okadaic acid, and calcium ionophore A23187, but not by phenobarbital or the
      steroid PP dehydroepiandrosterone sulfate. Induction of COX-2 expression
      generally resulted in increased synthesis of prostaglandin E2 (PGE2). However,
      the PPs caused little or no increase in PGE2 levels, and they inhibited serum
      induced PGE2 synthesis. Unlike non-steroidal anti-inflammatory drugs, the PPs do
      not directly inhibit cyclooxygenase enzyme activity in vitro. Thus, PPs regulate
      prostaglandin metabolism via both positive (COX-2 induction) and inhibitory
      mechanisms. In summary, the strong induction of COX-2 expression by PPs,
      thapsigargin, and okadaic acid suggests a possible role for COX-2 in the growth
      regulatory activity of these non-TPA-type tumor promoters.

PMID- 9013628
TI  - Cross-linking of DNA-binding proteins to DNA with psoralen and psoralen furan
      side monoadducts. Comparison of action spectra with DNA-DNA cross-linking.
AB  - We have developed a novel photocross-linking technique using free 8
      methoxypsoralen and DNA furan-side monoadducts plus long wave ultraviolet light
      (UVA). Both sequence-specific (Max) and nonspecific (RecA and T7 RNA polymerase)
      DNA-binding proteins were cross-linked. The macroscopic equilibrium binding
      constant ( approximately 10(9) M-1) and DNase I footprinting indicated that
      binding of Max to its cognate sequence (E-box) was unimpaired by 8
      methoxypsoralen and that cross-linking occurred in normal complexes. RecA protein
      and T7 RNA polymerase were cross-linked to a 12-mer DNA furan-side monoadduct
      with UVA. Cross-link yields were directly proportional to the UVA dose. Cross
      links were stable to 8 M urea, 1-10% SDS, commonly used alcohols, and mild acids
      (5% trichloroacetic acid). The DNA in cross-links was reversed with 254 nm UV
      (photoreversal) or with hot base (base-catalyzed reversal), consistent with (2 +
      2) cycloaddition via the 4',5'-furan of the psoralen. Comparative action spectra
      for DNA-DNA cross-linking and DNA-protein cross-linking revealed that the latter
      occurred maximally at 300 nm, while the former occurred maximally at 320 nm. This
      20-nm blue shift suggested a higher potential energy surface for an excited
      psoralen participating in protein-DNA cross-linking as compared with DNA-DNA
      cross-linking. As with DNA-DNA cross-linking, DNA-protein cross-linking is a two
      photon process. Absorption of the first photon formed a 4',5'-adduct with DNA,
      which then absorbed a second photon, leading to cross-linking to protein. Based
      on the action spectra and the known excited states of psoralen, it is suggested
      that the triplet n,pi* transition localized in the C-2=O of psoralen may be
      involved in protein-psoralen photoreactions.

PMID- 9013629
TI  - Expression of GTP-dependent and GTP-independent tissue-type transglutaminase in
      cytokine-treated rat brain astrocytes.
AB  - Tissue-type transglutaminases (TGases) were recently shown to exert dual
      enzymatic activities; they catalyze the posttranslational modification of
      proteins by transamidation, and they also act as guanosine triphosphatase
      (GTPase). Here we show that a tissue-type TGase is expressed in rat brain
      astrocytes in vitro, and is induced by the inflammation-associated cytokines
      interleukin-1beta and to a lesser extent by tumor necrosis factor-alpha.
      Induction is accompanied by overexpression and appearance of an additional
      shorter clone, which does not contain the long 3'-untranslated region and encodes
      for a novel TGase enzyme whose C terminus lacks a site that affects the enzyme's
      interaction with guanosine triphosphate (GTP). Expression of two clones revealed
      that the long form is inhibited noncompetitively by GTP, but the short form
      significantly less so. The different affinities for GTP may account for the
      difference in physiological function between these two enzymes.

PMID- 9013630
TI  - Overlapping expression and redundant activation of mesenchymal fibroblast growth
      factor (FGF) receptors by alternatively spliced FGF-8 ligands.
AB  - FGF-8 is a member of the family of fibroblast growth factors and is expressed
      during vertebrate embryo development. Eight potential FGF-8 isoforms are
      generated by alternative splicing in mice, several of which are expressed during
      embryogenesis in epithelial locations. The significance of the multiple isoforms
      is currently unknown. In this report, we investigate the expression patterns and
      the specificity of the FGF-8 isoforms for known fibroblast growth factor (FGF)
      receptors. RNAs for seven of the eight potential isoforms are present at multiple
      sites of embryonic Fgf8 expression. None of the FGF-8 isoforms exhibited activity
      when assayed with BaF3 cells expressing the "b" splice forms of FGF receptors 1
      3, which are mostly expressed in epithelial tissues. Mesenchymally expressed "c"
      splice forms of FGF receptors 2 and 3 and FGF receptor 4 were activated by
      several FGF-8 isoforms. These findings are consistent with the hypothesis that
      the multiple FGF-8 isoforms are functionally redundant and function to signal in
      paracrine (epithelial to mesenchymal) contexts.

PMID- 9013631
TI  - Multiple classes of sulfhydryls modulate the skeletal muscle Ca2+ release
      channel.
AB  - Two sulfhydryl reagents, N-ethylmaleimide (NEM), an alkylating agent, and
      diamide, an oxidizing agent, were examined for effects on the skeletal muscle
      Ca2+ release channel. NEM incubated with the channel for increasing periods of
      time displays three distinct phases in its functional effects on the channel
      reconstituted into planar lipid bilayers; first it inhibits, then it activates,
      and finally it again inhibits channel activity. NEM also shows a three-phase
      effect on the binding of [3H]ryanodine by first decreasing binding (phase 1),
      followed by a recovery of the binding (phase 2), and then a final phase of
      inhibition (phase 3). In contrast, diamide 1) activates the channel, 2) enhances
      [3H]ryanodine binding, 3) cross-links subunits within the Ca2+ release channel
      tetramer, and 4) protects against phase 1 inhibition by NEM. All diamide effects
      can be reversed by the reducing agent, dithiothreitol. Diamide induces
      intersubunit dimer formation of both the full-length 565-kDa subunit of the
      channel and the 400-kDa generated by endogenous calpain digestion, suggesting
      that the cross-link does not involve sulfhydryls within the N-terminal 170-kDa
      fragment of the protein. NEM under phase 1 conditions blocks the formation of the
      intersubunit cross-links by diamide. In addition, single channels activated by
      diamide are further activated by the addition of NEM. Diamide either cross-links
      phase 1 sulfhydryls or causes a conformational change in the Ca2+ release channel
      which leads to inaccessibility of phase 1 sulfhydryls to NEM alkylation. The data
      presented here lay the groundwork for mapping the location of one of the sites of
      subunit-subunit contact in the Ca2+ release channel tetramer and for identifying
      the functionally important sulfhydryls of this protein.

PMID- 9013632
TI  - Trypanosoma brucei gBP21. An arginine-rich mitochondrial protein that binds to
      guide RNA with high affinity.
AB  - RNA editing in Trypanosoma brucei is a mitochondrial RNA processing reaction that
      results in the insertion and deletion of uridylate residues into otherwise
      untranslatable mRNAs. The process is directed by guide RNAs which function to
      specify the edited sequence. RNA editing in vitro requires mitochondrial protein
      extracts and guide RNAs have been identified as part of high molecular weight
      ribonucleoprotein complexes. Within the complexes, the RNAs are in close contact
      with several mitochondrial proteins and here we describe the isolation and
      cloning of a gRNA-interacting polypeptide from Trypanosoma brucei. The protein
      was named gBP21 for guide RNA-binding protein of 21 kDa. gBP21 shows no homology
      to proteins in other organisms, it is arginine-rich and binds to gRNA molecules
      with a dissociation constant in the nanomolar range. The protein does not
      discriminate for differences in the primary structures of gRNAs and thus likely
      binds to higher order structural features common to all gRNA molecules. gBP21
      binding does not perturb the overall structure of gRNAs but the gRNA/gBP21
      ribonucleoprotein complex is more stable than naked guide RNAs. Although the
      protein is arginine-rich, the free amino acid or an arginine-rich peptide were
      not able to inhibit the association to the RNAs. In contrast, the gRNA-gBP21
      complex formation was sensitive to potassium and ammonium cations, thus
      indicating a contribution of ionic contacts to the binding.

PMID- 9013633
TI  - Characterization of VNFG, the delta subunit of the vnf-encoded apodinitrogenase
      from Azotobacter vinelandii. Implications for its role in the formation of
      functional dinitrogenase 2.
AB  - The vnf-encoded apodinitrogenase (apodinitrogenase 2) from Azotobacter vinelandii
      is an alpha2beta2delta2 hexamer. The delta subunit (the VNFG protein) has been
      characterized in order to further delineate its function in the nitrogenase 2
      enzyme system. Two species of VNFG were observed in cell-free extracts resolved
      on anoxic native gels; one is composed of VNFG associated with the VNFDK
      polypeptides, and the other is a homodimer of the VNFG protein. Both species of
      VNFG are observed in extracts of A. vinelandii strains that accumulate
      dinitrogenase 2, whereas extracts of strains impaired in the biosynthetic pathway
      of the iron-vanadium cofactor (FeV-co) that accumulate apodinitrogenase 2 (a
      catalytically inactive form of dinitrogenase 2 that lacks FeV-co) exhibit only
      the VNFG dimer on native gels. FeV-co and nucleotide are required for the stable
      association of VNFG with the VNFDK polypeptides; this stable association can be
      correlated with the formation of active dinitrogenase 2. The iron-molybdenum
      cofactor was unable to replace FeV-co in promoting the stable association of VNFG
      with VNFDK. FeV-co specifically associates with the VNFG dimer in vitro to form a
      complex of unknown stoichiometry; combination of this VNFG-FeV-co species with
      apodinitrogenase 2 results in its reconstitution to dinitrogenase 2. The results
      presented here suggest that VNFG is required for processing apodinitrogenase 2 to
      functional dinitrogenase 2.

PMID- 9013635
TI  - Specific interaction between casein kinase 2 and the nucleolar protein Nopp140.
AB  - Casein kinase 2 (CK2) is a multifunctional second messenger-independent protein
      serine/threonine kinase that phosphorylates many different proteins. To
      understand the function and regulation of this enzyme, biochemical methods were
      used to search for CK2-interacting proteins. Using immobilized glutathione S
      transferase fusion proteins of CK2, the nucleolar protein Nopp140 was identified
      as a CK2-associated protein. It was found that Nopp140 binds primarily to the CK2
      regulatory subunit, beta. The possible in vivo association of Nopp140 with CK2
      was also suggested from a coimmunoprecipitation experiment in which Nopp140 was
      detected in immunoprecipitates of CK2 prepared from cell extracts. Further
      studies using an overlay technique with radiolabeled CK2 as a probe revealed a
      direct CK2-Nopp140 interaction. Using deletion mutants of CK2beta subunits, the
      binding region of the CK2beta subunit to Nopp140 has been mapped. It was found
      that the NH2-terminal 20 amino acids of CK2beta are involved. Since Nopp140 has
      been identified as a nuclear localization sequence-binding protein and has been
      shown to shuttle between the cytoplasm and the nucleus, the finding of a CK2
      Nopp140 interaction could shed light on our understanding of the function and
      regulation of CK2 and Nopp140.

PMID- 9013634
TI  - Organization and expression of the mouse MTH1 gene for preventing transversion
      mutation.
AB  - An enzyme, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase), is
      present in various organisms and plays an important role in the control of
      spontaneous mutagenesis. The enzyme hydrolyzes 8-oxo-dGTP, an oxidized form of
      dGTP, to 8-oxo-dGMP, thereby preventing the occurrence of A:T to C:G
      transversion, caused by misincorporation. We isolated the mouse genomic sequence
      encoding the enzyme and elucidated its structure. The gene, named MTH1 for mutT
      homologue 1, is composed of at least five exons and spans approximately 9
      kilobase pairs. A genomic region containing the pseudogene was also isolated. The
      promoter region for the gene is GC-rich, contains many AP-1 and AP-2 recognition
      sequences, and lacks a typical TATA box. Primer extension and S1 mapping analyses
      revealed the existence of multiple transcription initiation sites, among which a
      major site was defined as +1. The putative promoter region was placed upstream of
      the chloramphenicol acetyltransferase reporter gene, and control of expression of
      the gene was examined by introducing the construct into mouse NIH 3T3 cells.
      Deletion analysis indicated that a sequence from -321 to +9 carries the basic
      promoter activity while an adjacent region, spanning from +352 to +525 stimulates
      the frequency of transcription.

PMID- 9013636
TI  - The proto-oncogene product p120(cbl) links c-Src and phosphatidylinositol 3'
      kinase to the integrin signaling pathway.
AB  - Integrin-mediated cell adhesion triggers intracellular signaling cascades,
      including tyrosine phosphorylation of intracellular proteins. We show in this
      report that p120(cbl) (Cbl), the 120-kDa c-cbl proto-oncogene product, becomes
      tyrosine-phosphorylated during integrin-mediated macrophage cell adhesion to
      extracellular matrix substrata and anti-integrin antibodies. This tyrosine
      phosphorylation does not occur when cells attach to polylysine, to which cells
      adhere in a nonspecific fashion. It also does not take place when adhesion
      induced reorganization of the cytoskeleton is inhibited with cytochalasin D. In
      contrast to the rapid and transient tyrosine phosphorylation of Cbl by CSF-1
      stimulation, tyrosine phosphorylation of Cbl by cell attachment was gradual and
      persistent. Tyrosine-phosphorylated Cbl was found to form complexes with the SH2
      domain-containing signaling proteins Src and phosphatidylinositol 3-kinase; in
      vitro kinase assays demonstrated that these kinases were active in the Cbl
      complexes following integrin ligand binding. Furthermore, Cbl was found to
      translocate to the plasma membrane in response to cell adhesion to fibronectin.
      These observations suggest that Cbl serves as a docking protein and may transduce
      signals to downstream signaling pathways following integrin-mediated cell
      adhesion in macrophages.

PMID- 9013637
TI  - Identification of domains on the extrinsic 33-kDa protein possibly involved in
      electrostatic interaction with photosystem II complex by means of chemical
      modification.
AB  - The extrinsic 33-kDa protein of photosystem II (PSII) was modified with various
      reagents, and the resulting proteins were checked for the ability to rebind to
      PSII and to reactivate oxygen evolution. While modification of more than eight
      carboxyl groups of aspartyl and glutamyl residues with glycine methyl ester did
      not affect the rebinding and reactivating capabilities, modification of amino
      groups of lysyl residues with either N-succinimidyl propionate or 2, 4,6
      trinitrobenzene sulfonic acid or modification of guanidino groups of arginyl
      residues with 2,3-butanedione resulted in a loss of rebinding and reactivating
      capabilities of the 33-kDa protein. Moreover, the number of lysyl and arginyl
      residues susceptible to modification was significantly decreased when the protein
      was bound to PSII as compared with when it was free in solution, whereas the
      number of carboxyl groups modified was little affected. These results suggested
      that positive charges are important for the electrostatic interaction between the
      extrinsic 33-kDa protein and PSII intrinsic proteins, whereas negative charges on
      the protein do not contribute to such interaction. By a combination of protease
      digestion and mass spectroscopic analysis, the domains of lysyl residues
      accessible to N-succinimidyl propionate or 2,4, 6-trinitrobenzene sulfonic acid
      modification only when the 33-kDa protein is free in solution were determined to
      be Lys4, Lys20, Lys66-Lys76, Lys101, Lys105, Lys130, Lys159, Lys186, and Lys230
      Lys236. These domains include those previously reported accessible to N
      hydroxysuccinimidobiotin only in solution (Frankel and Bricker (1995)
      Biochemistry 34, 7492-7497), and may be important for the interaction of the 33
      kDa protein with PSII intrinsic proteins.

PMID- 9013638
TI  - Golgi GDP-mannose uptake requires Leishmania LPG2. A member of a eukaryotic
      family of putative nucleotide-sugar transporters.
AB  - The synthesis of glycoconjugates within the secretory pathway of eukaryotes
      requires the provision of lumenal nucleotide-sugar substrates. This is
      particularly important for eukaryotic microbes such as Leishmania because they
      must synthesize considerable amounts of extracellular and cell surface
      glycoconjugates that play significant roles in the infectious cycle. Here we used
      properly oriented sealed microsomes to characterize lumenal uptake of GDP-Man in
      Leishmania donovani. In this system, GDP-Man uptake was saturable with an
      apparent Km for GDP-Man of 0.3 microM and facilitated its use as a donor
      substrate for lipophosphoglycan (LPG) synthesis. A lpg2(-) deletion mutant showed
      loss of GDP-Man but not UDP-Gal uptake, which was restored by introduction of the
      gene LPG2. Immunoelectron microscopy localized an active, epitope-tagged LPG2
      protein to the Golgi apparatus. Thus, LPG2 is required for nucleotide-sugar
      transport activity and probably encodes this Golgi transporter. LPG2 belongs to a
      large family of eukaryotic genes that potentially encode transporters with
      different substrate specificities and/or cellular locations. In the future, the
      amenability of the Leishmania system to biochemical and genetic manipulation will
      assist in functional characterization of nucleotide-sugar transports from this
      and other eukaryotes. Furthermore, since LPG2 plays an important role in the
      Leishmania infectious cycle and mammalian cells lack a Golgi GDP-Man transporter,
      this activity may offer a new target for chemotherapy.

PMID- 9013639
TI  - Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C.
AB  - G protein-coupled receptor kinases (GRKs) specifically recognize and
      phosphorylate the hormone-occupied form of numerous G protein-coupled receptors,
      ultimately resulting in termination of receptor signaling. While little is
      presently known about the regulation of GRK function, recent studies suggest a
      role for protein kinase C (PKC) phosphorylation of the beta-adrenergic receptor
      kinase in membrane association and activation of the kinase. To assess a
      potential general role for PKC in regulating GRK function, we characterized the
      ability of PKC to phosphorylate GRK5, a recently identified member of the GRK
      family. We demonstrate that GRK5 can be rapidly and stoichiometrically
      phosphorylated by PKC in vitro. Intact cell studies reveal that GRK5 is also
      phosphorylated when transiently expressed in COS-1 cells following treatment with
      the PKC activator, phorbol 12-myristate 13-acetate. In vitro analysis reveals two
      major sites of PKC phosphorylation within the C-terminal 26 amino acids of GRK5.
      GRK5 phosphorylation by PKC dramatically reduces its ability to phosphorylate
      both receptor (light-activated rhodopsin) and non-receptor (casein and phosvitin)
      substrates. Kinetic analysis reveals an approximately 5-fold increased Km and
      approximately 3-fold decreased Vmax for rhodopsin, with no change in the Km for
      ATP. The reduced affinity of PKC-phosphorylated GRK5 for rhodopsin was also
      evident in a decreased ability to bind to rhodopsin-containing membranes, while
      direct binding of GRK5 to phospholipids appeared unaltered. These results suggest
      that PKC might play an important role in modulating the ability of GRK5 to
      regulate receptor signaling and that GRK phosphorylation by PKC may serve as a
      disparate mechanism for regulating GRK activity.

PMID- 9013640
TI  - Detection and functional characterization of p180, a novel cell cycle regulated
      yeast transcription factor that binds retinoblastoma control elements.
AB  - In recent years it has become apparent that the cellular machinery governing cell
      cycle progression and transcription control are often homologous in yeast and
      mammalian cells. We and others have previously shown that the SP family of
      mammalian transcription factors regulates the transcription of a number of genes
      whose activities are governed by the product of the retinoblastoma (Rb)
      susceptibility gene, including c-FOS, c-MYC, TGFbeta-1, IGF-II, and c-JUN. To
      determine whether a similar pathway of transcriptional regulation may function in
      yeast, we explored the possibility that transcription factors with nucleotide
      binding specificities akin to those of the SP family are expressed in
      Saccharomyces cerevisiae and Schizosaccharomyces pombe. Here we report the
      detection of novel yeast proteins (S. cerevisiae, p180; S. pombe, p200) that
      specifically bind Rb-regulated promoter elements in vitro dependent on
      nucleotides that are also required for binding and trans-activation by SP family
      members in vivo. Our results indicate that the S. cerevisiae retinoblastoma
      control element-binding activity 1) requires zinc for association with DNA; 2)
      does not bind to SCB, MCB, or E2F sites in vitro; 3) is cell cycle-regulated in a
      SWI6-independent fashion; and 4) maximally stimulates retinoblastoma control
      element-mediated transcription in early- to mid-S phase. Taken together, these
      data suggest that p180 may regulate the transcription of a subset of yeast genes
      whose expression is coincident with the onset and/or progression of DNA
      replication.

PMID- 9013641
TI  - Characterization of putative human homologues of the yeast chromosome
      transmission fidelity gene, CHL1.
AB  - Helicases are components of numerous protein complexes, including those
      regulating transcription, translation, DNA replication and repair, splicing, and
      mitotic chromosome transmission. Helicases unwind double-stranded DNA and RNA
      homo- and hetero-duplexes. The yeast CHL1 helicase has been linked to maintenance
      of the high fidelity of chromosome transmission during mitosis. Mutations in this
      gene result in a 200-fold increase in the rate of aberrant chromosome segregation
      with a concomitant delay in the cell cycle at G2-M, suggesting that CHL1 is
      required for the maintenance of proper chromosome transmission. Two highly
      related human cDNA clones encoding proteins which are homologous to the yeast
      CHL1 gene product have been isolated. Here we show that these two distinct human
      CHL1-related mRNAs and proteins (hCHLR1 and hCHLR2) are expressed only in
      proliferating human cell lines. Quiescent normal human fibroblasts stimulated to
      re-enter the cell cycle by addition of serum begin to express the CHL1-related
      proteins as the cells enter S phase, concomitant with the expression of
      proliferating cell nuclear antigen. Furthermore, expression of the CHL1-related
      mRNAs is lost when human K562 cells cease to proliferate and terminally
      differentiate in response to phorbol ester treatments. Human hCHLR expression is
      not extinguished during hemin-induced differentiation of the same cell line,
      which produces erythrocyte-like cells that continue to proliferate. These
      experiments are consistent with the requirement of this putative helicase during
      either S or G2-M phase but not G1. In vitro transcribed and translated hCHLR1
      protein binds to both single- and double-stranded DNA, supporting the possibility
      that these proteins are DNA helicases. Finally, affinity-purified hCHLR1 antisera
      was used to demonstrate the localization of the hCHLR proteins to the nucleolus
      by indirect immunofluorescence as well as by cell fractionation.

PMID- 9013642
TI  - Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex.
AB  - The human XPF-ERCC1 protein complex is one of several factors known to be
      required for general nucleotide excision repair. Genetic data indicate that both
      proteins of this complex are necessary for the repair of interstrand cross-links,
      perhaps via recombination. To determine whether XPF-ERCC1 completes a set of six
      proteins that are sufficient to carry out excision repair, the human XPF and
      ERCC1 cDNAs were coexpressed in Sf21 insect cells from a baculovirus vector. The
      purified complex contained the anticipated 5' junction-specific endonuclease
      activity that is stimulated through a direct interaction between XPF and
      replication protein A (RPA). The recombinant complex also complemented extracts
      of XP-F cells and Chinese hamster ovary mutants assigned to complementation
      groups 1, 4, and 11. Furthermore, reconstitution of the human excision nuclease
      was observed with a mixture of five repair factors (XPA, XPC, XPG, TFIIH, and
      RPA) and the recombinant XPF-ERCC1, thus verifying that no additional protein
      factors are needed for the specific dual incisions characteristic of human
      excision repair.

PMID- 9013643
TI  - Co-ligation of the antigen and Fc receptors gives rise to the selective
      modulation of intracellular signaling in B cells. Regulation of the association
      of phosphatidylinositol 3-kinase and inositol 5'-phosphatase with the antigen
      receptor complex.
AB  - Cross-linking of the Fc receptor (FcR) to surface immunoglobulin (sIg) on B cells
      inhibits the influx of extracellular calcium and abrogates the proliferative
      signal. The mechanism by which this occurs is not well understood. In this report
      we show that co-cross-linking the FcR to the antigen receptor gives rise to very
      selective modulation of signal transduction in B cells. Co-cross-linking sIg and
      the FcR enhanced the phosphorylation of the FcR, the adapter protein, Shc, and
      the inositol 5'-phosphatase Ship. Furthermore, phosphorylation of the FcR induced
      its association with Ship. Cross-linking of the FcR and sIg decreased the
      tyrosine phosphorylation of CD19, which led to a reduction in the association of
      phosphatidylinositol 3-kinase. In addition, the phosphorylation of several other
      proteins of 73, 39, and 34 kDa was reduced. Activation of the cells with either
      F(ab')2 or intact anti-IgG induced very similar changes in levels of tyrosine
      phosphorylation of most other proteins, and no differences in the activation of
      several protein kinases were observed. These results indicate that the inhibitory
      signal that is transmitted through the FcR is not mediated by a global shutdown
      of tyrosine phosphorylation but is, rather, a selective mechanism involving
      localized changes in the interactions of adapter proteins and the enzymes Ship
      and phosphatidylinositol 3-kinase with the antigen receptor complex.

PMID- 9013644
TI  - Degradation of E2A proteins through a ubiquitin-conjugating enzyme, UbcE2A.
AB  - The helix-loop-helix E2A proteins (E12 and E47) govern cellular growth and
      differentiation. To identify binding partners that regulate the function of these
      ubiquitous transcription factors, we screened for proteins that interacted with
      the C terminus of E12 by the yeast interaction trap. UbcE2A, a rat enzyme that is
      highly homologous to and functionally complements the yeast ubiquitin-conjugating
      enzyme UBC9, was identified and cloned. UbcE2A appears to be an E2A-selective
      ubiquitin-conjugating enzyme because it interacts specifically with a 54-amino
      acid region in E47-(477-530) distinct from the helix-loop-helix domain. In
      contrast, most of the UbcE2A protein is required for interaction with an E2A
      protein. The E2A proteins appear to be degraded by the ubiquitin-proteasome
      pathway because the E12 half-life of 60 min is extended by the proteasome
      inhibitor MG132, and E12 is multi-ubiquitinated in vivo. Finally, antisense
      UbcE2A reduces E12 degradation. By participating in the degradation of the E2A
      proteins, UbcE2A may regulate cell growth and differentiation.

PMID- 9013645
TI  - Transcription of the Acanthamoeba TATA-binding protein gene. A single
      transcription factor acts both as an activator and a repressor.
AB  - Transcription of the Acanthamoeba TATA-binding protein (TBP) gene is regulated by
      TBP promoter-binding factor (TPBF), a previously described transactivator that
      binds as a tetramer to the TBP Promoter Element (TPE) and stimulates
      transcription up to 10-fold in vitro. Here we report that TPBF also functions as
      a transcription repressor by binding to a negative cis-element, located between
      the TATA box and the transcription initiation site. The negative element,
      referred to as the nTPE, is structurally similar to the TPE, and its disruption
      increases the transcription potency of the TBP promoter. TPBF binds to the nTPE,
      as demonstrated by mobility shift assays. However, the binding affinity of TPBF
      for the nTPE is about 10-fold lower than for the TPE. When placed upstream of the
      TATA box, the nTPE has very little effect on transcription. However, it inhibits
      transcription when placed at several positions downstream of the TATA box.
      Mechanistic studies with the TBP promoter suggest that binding of TPBF to the
      nTPE not only prevents TBP from binding to the TATA box but also displaces bound
      TBP, thereby inhibiting further assembly of the preinitiation complex. These
      results suggest a mechanism in which the cellular TPBF concentration controls the
      level of TBP gene transcription and show that a single factor can be stimulatory,
      inhibitory, or neutral depending on the sequence and the context of its binding
      site.

PMID- 9013646
TI  - Characterization of two alternately spliced forms of phospholipase D1. Activation
      of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP
      ribosylation factor, and Rho family monomeric GTP-binding proteins and protein
      kinase C-alpha.
AB  - We previously reported the cloning of a cDNA encoding human phosphatidylcholine
      specific phospholipase D1 (PLD1), an ADP-ribosylation factor (ARF)-activated
      phosphatidylcholine-specific phospholipase D (Hammond, S. M., Tsung, S.,
      Autschuller, Y., Rudge, S. A., Rose, K., Engebrecht, J., Morris, A. J., and
      Frohman, M. A. (1995) J. Biol. Chem. 270, 29640-29643). We have now identified an
      evolutionarily conserved shorter splice variant of PLD1 lacking 38 amino acids
      (residues 585-624) that arises from regulated splicing of an alternate exon. Both
      forms of PLD1 (PLD1a and 1b) have been expressed in Sf9 cells using baculovirus
      vectors and purified to homogeneity by detergent extraction and immunoaffinity
      chromatography. PLD1a and 1b have very similar properties. PLD1a and 1b activity
      is Mg2+dependent but insensitive to changes in free Ca2+ concentration.
      Phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5
      trisphosphate activate PLD1a and 1b but a range of other acidic phospholipids are
      ineffective. PLD1a and 1b are highly responsive to activation by GTP-gammaS
      liganded ADP-ribosylation factor-1 (ARF-1) and can also be activated to a lesser
      extent by three purified RHO family monomeric GTP-binding proteins, RHO A, RAC-1,
      and CDC42. Activation of PLD1a and 1b by the RHO family monomeric GTP-binding
      proteins is GTP-dependent and synergistic with ARF-1. Purified protein kinase C
      alpha activates PLD1a and 1b in a manner that is stimulated by phorbol esters and
      does not require ATP. Activation of PLD1a and 1b by protein kinase C-alpha is
      synergistic with ARF and with the RHO family monomeric GTP-binding proteins,
      suggesting that these three classes of regulators interact with different sites
      on the enzyme.

PMID- 9013647
TI  - DNA computing.
AB  - DNA computation is a novel and exciting recent development at the interface of
      computer science and molecular biology. We describe the current activity in this
      field following the seminal work of Adleman, who recently showed how techniques
      of molecular biology may be applied to the solution of a computationally
      intractable problem.

PMID- 9013648
TI  - High-speed DNA sequencing in ultrathin slab gels.
AB  - There have been many recent theoretical and technical advances in the sequencing
      of DNA in ultrathin slab gels. These include recent experimental progress in four
      areas: DNA polymerases; DNA template preparation; the separation and detection of
      DNA bands; and base-calling algorithms. The Zimm-Lumpkin theory of
      electrophoresis provides a new and improved framework for understanding the
      operation of sequencing gels.

PMID- 9013649
TI  - Quantitative nucleic acids footprinting: thermodynamic and kinetic approaches.
AB  - Quantitative footprinting techniques allow a detailed analysis of the
      thermodynamic forces that characterize nucleic acid-ligand interactions and
      ligand-induced changes in nucleic acid structure by separately resolving the
      intrinsic and cooperative Gibbs free energy changes describing the reactions
      being investigated. A new implementation of the quantitative footprinting
      technique is the application of stopped-flow techniques to the study of kinetic
      reactions.

PMID- 9013650
TI  - Fluorescence spectroscopy as a tool to investigate protein interactions.
AB  - Recent advances in the use of fluorescence spectroscopy to study protein
      interactions have primarily involved combinations of classic fluorescence
      techniques, novel probe and coupling chemistries, and advances in laser
      excitation and detection capabilities. For example, new coupling strategies for
      fluorescent probes have allowed the first determination of the DeltaG&deg;
      describing the insertion of a protein into a membrane. Fluorescently labeled
      oligonucleotides with specific protein-binding sequences have been used to study
      both protein-DNA associations and oligonucleotide hybridization using anisotropy
      changes. The first kinetic data describing a DNA-protein binding event was
      collected with stopped-flow fluorescence instrumentation. Combining scanning
      fluctuation correlation spectroscopy with a two-photon excitation source improved
      this technique so that it may now be used to study protein self-associations.

PMID- 9013651
TI  - Optical mapping approaches to molecular genomics.
AB  - A variety of physical mapping methods exist for the analysis of nucleic acids or
      genomes, including hybridization, sequence tagged site mapping, restriction
      enzyme fingerprinting, radiation hybrid mapping and optical mapping. Single
      molecule approaches offer numerous advantages, including very high resolution,
      small sample size requirements, and parallel sample processing. The convergence
      of recent advances in new single molecule techniques, surface chemistry and
      machine vision technology has contributed to novel approaches to genome analysis.

PMID- 9013652
TI  - RecA-mediated Achilles' heel cleavage.
AB  - The specific protection of only one of many restriction sites in a genome from
      inactivation by a cognate methyltransferase (MTase) creates a unique cleavage
      site - an Achilles' heel cleavage (AC) site. In the RecA-AC, or RARE, technique,
      such specific protection is provided by a synaptic complex composed of RecA
      protein, a gamma-S analog of ATP and a 30-60 nucleotide long oligodeoxynucleotide
      complementary or identical to the sequence-targeted site in which the protected
      restriction site is embedded. Upon methylation and the subsequent removal of the
      protective complex and MTase, the protected site is the only site cut by the
      cognate restriction enzyme. Two such targeted cuts permit the excision of a
      unique DNA fragment from the genome. Recent advances include the calibration of
      DNA clones, the mapping of gaps, and the determination of the sizes of excised
      fragments by pulsed-field gel electrophoresis, which allows one to measure
      distances between any two neighboring sequence-targeted sites, in the range of a
      few kilobases to 10 megabases, with the purpose of physically mapping the genome.

PMID- 9013653
TI  - Replaceable polymers in DNA sequencing by capillary electrophoresis.
AB  - Much progress has been made in the development of replaceable sieving polymers
      and capillary coatings for high-performance DNA sequencing by capillary
      electrophoresis. Several studies of parameters that affect resolution, read
      length and reproducibility have begun to reveal the physical mechanisms acting on
      single-stranded DNA during electrophoresis through semidilute polymer solutions.
      Recently developed electro-osmosis-inhibiting matrix polymers have simplified the
      process of coating capillaries, facilitating the automation of high-throughput
      parallel systems for large-scale sequencing.

PMID- 9013654
TI  - Energy-transfer fluorescent reagents for DNA analyses.
AB  - Fluorescence resonance energy transfer has facilitated the development of a new
      class of high-performance fluorescent labeling reagents for multiplex analyses of
      nucleic acids. The enhanced emission of energy transfer (ET) primers has provided
      a decadic improvement in the performance of automated DNA sequencers. The
      emission spectral purity of ET primers permits the development of robust
      multiplex diagnostic methods for the detection of PCR products. High affinity
      bifunctional intercalation reagents containing ET-coupled dyes are also being
      used for high-performance multiplex assays of double-stranded DNA when
      noncovalent labeling is preferred.

PMID- 9013655
TI  - Total internal reflection fluorescence: applications in cellular biophysics.
AB  - Molecular interactions occurring on or near cell membrane surfaces are expected
      to have different properties from those occurring in bulk solutions. One
      particularly useful technique for studying surface-associated processes at the
      molecular level is total internal reflection fluorescence. In this method, the
      evanescent field from an internally reflected excitation source selectively
      excites fluorescent molecules on or near a surface. Evanescent excitation has
      been used recently with a variety of techniques in fluorescence microscopy and
      spectroscopy to probe the fundamental physicochemical properties of biochemical
      reactions at natural or model biological surfaces. These studies are providing
      enhanced understanding of cellular function. Several recent developments in total
      internal reflection fluorescence methodology from other fields are likely to find
      future application in cellular biophysics.

PMID- 9013656
TI  - Influence of excluded volume upon macromolecular structure and associations in
      'crowded' media.
AB  - Results of experimental studies published since the last major review of excluded
      volume effects in biopolymer solutions in 1993 add to our appreciation of the
      scope and magnitude of such effects. Recent theoretical studies have improved
      incrementally our ability to understand and model excluded volume effects in
      simple model systems.

PMID- 9013657
TI  - Mass spectrometry in protein studies from genome to function.
AB  - The demands for highly sensitive and specific analytical techniques in
      biochemistry, molecular biology and biotechnology are met by new developments in
      mass spectrometry. Femto- to attomole sensitivity and mass accuracy in a low
      parts per million range can now be routinely obtained. Mass spectrometry, already
      accepted for studies of protein secondary modifications, must, in the future, be
      expected to be an important tool in protein studies on all levels, ranging from
      proteome analysis to studies of protein higher order structures and protein
      interaction.

PMID- 9013658
TI  - Characterization of binding interactions by isothermal titration calorimetry.
AB  - Isothermal titration calorimetry is a high-accuracy method for measuring binding
      affinities. Titration calorimetry is a universal method that has broad impact
      throughout biotechnology. In recent years, microcalorimeters that are capable of
      characterizing binding interactions of biological macromolecules have become
      commercially available. Results from these studies are providing new insight into
      the molecular nature of macromolecular interactions.

PMID- 9013659
TI  - Kinetic analysis of macromolecular interactions using surface plasmon resonance
      biosensors.
AB  - Surface plasmon resonance based biosensors are being used to define the kinetics
      of a wide variety of macromolecular interactions. As the popularity of this
      approach grows, experimental design and data analysis methods continue to evolve.
      These advances are making it possible to accurately define the assembly
      mechanisms and rate constants associated with macromolecular interactions.

PMID- 9013660
TI  - Static and dynamic light scattering of biological macromolecules: what can we
      learn?
AB  - Laser light scattering comes in two major 'flavors': dynamic and static. This
      noninvasive technique provides a means for investigating key size and shape
      properties of macromolecules in solution. Light scattering has long been an
      indispensable tool to the polymer physical chemist, and is seeing increased use
      in exploring properties of biological macromolecules, alone and in association.
      As examples, recent investigations using light scattering have clearly
      demonstrated the relationship between the self-association and activity of
      important regulatory enzymes, and examined conformational properties of DNA and
      polysaccharides.

PMID- 9013661
TI  - Sedimentation velocity spins a new weave for an old fabric.
AB  - Sedimentation velocity analysis is a powerful tool for the investigation of
      biological macromolecules under a wide range of solution conditions. If carefully
      applied, it can be an effective tool for the characterization of interacting
      systems in solution. It is rapidly becoming a method of choice among the
      biotechnology community. In recent years, there have been notable advances in the
      ease of acquisition and analysis of analytical ultracentrifugation data.

PMID- 9013662
TI  - Web alert. Analytical biotechnology.

PMID- 9013663
TI  - The biologist and the World Wide Web: an overview of the search engines
      technology, current status and future perspectives.

PMID- 9013664
TI  - Analytical biotechnology.

PMID- 9013665
TI  - Microtubules and axonal growth.
AB  - Twenty years of controversy have not produced a consensus concerning the
      mechanisms by which the microtubule array of the growing neuronal axon is
      established. At the heart of the controversy is the issue of whether tubulin is
      actively transported down the axon as assembled microtubules or as free subunits.
      This past year has seen the publication of several new studies relevant to this
      exciting and fundamental issue. Some of these studies failed to reveal evidence
      for the transport of assembled microtubules. Other studies, however, that used
      exciting new pharmacological, live-cell and molecular approaches, provide
      compelling new evidence that assembled microtubules are indeed the form in which
      tubulin is actively transported down the axon.

PMID- 9013666
TI  - Myosins in yeast.
AB  - It has been a banner year for the study of yeast myosins. Thanks to the
      completion of the Saccharomyces cerevisiae genome project, it is now known that
      budding yeast contains a total of five myosins. Furthermore, functions have been
      newly ascribed to several of them: two have been implicated in endocytosis, and
      another has been implicated in generating asymmetry between mother and daughter
      cells.

PMID- 9013667
TI  - The structure of microtubule-motor complexes.
AB  - New images, calculated from electron micrographs, show the three-dimensional
      structures of microtubules and tubulin sheets decorated stoichiometrically with
      globular motor protein domains (heads). Single heads of kinesin and ncd, the
      kinesin-related protein that moves in the reverse direction to kinesin, bind in
      the same way to the same site on tubulin. Dimeric kinesin and dimeric ncd show an
      interesting difference in the positions of their second heads.

PMID- 9013668
TI  - Cell anchorage and the cytoskeleton as partners in growth factor dependent cell
      cycle progression.
AB  - Several studies in the past year have shown that the cell cycle events typically
      attributed to a response to growth factors actually require signals provided by
      both growth factors and the extracellular matrix. Moreover, at least some of
      these matrix-based effects seem to involve matrix-dependent organization of the
      cytoskeleton rather than cell adhesion per se. Overall, these studies are
      providing new insights into the long-appreciated concepts of anchorage- and shape
      dependent growth.

PMID- 9013669
TI  - Actin dynamics in vivo.
AB  - Actin dynamics in lamellipodia are driven by continuous cycles of actin
      polymerization, retrograde flow, and depolymerization. In the past year, advances
      have been made in identifying signaling pathways that regulate actin-filament
      uncapping and polymerization, in determining the role of myosin motor proteins in
      retrograde flow, and in evaluating the role of severing proteins in actin
      depolymerization. Both Listeria monocytogenes and Saccharomyces cerevisiae have
      emerged as powerful model organisms for studying actin dynamics in cells.

PMID- 9013670
TI  - Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton.
AB  - Rho, Rac and Cdc42 are three Ras-related GTP-binding proteins that control the
      assembly and disassembly of the actin cytoskeleton in response to extracellular
      signals. During the past year, numerous candidate downstream targets for these
      GTPases have been identified using affinity chromatography and yeast two-hybrid
      techniques. These techniques have revealed that Rho regulates the myosin light
      chain phosphatase and that Rho and Rac control the synthesis of
      phosphatidylinositol 4,5-bisphosphate, two activities that might help to explain
      the effects of these GTPases on the actin cytoskeleton.

PMID- 9013671
TI  - Pathways of spindle assembly.
AB  - Recent studies have revealed that, in some systems, chromatin has the ability to
      stabilize microtubules and organize them into bipolar spindles independently of
      kinetochores and centrosomes. In addition, several molecules have been identified
      recently that are necessary for spindle assembly; these include proteins that
      regulate microtubule dynamics, proteins that organize microtubule minus ends into
      spindle poles, and members of the kinesin superfamily that reside on the
      chromosome arms.

PMID- 9013672
TI  - Cytoskeletal and adhesion proteins as tumor suppressors.
AB  - In the past year, significant progress has been made in the attempt to understand
      the molecular mechanisms underlying signaling that is induced by cell-cell and
      cell-extracellular-matrix adhesion and that involves the cytoskeleton. In
      particular, molecules of the cytoplasmic plaques of cell-cell junctions have been
      shown to complex with transcription factors and to translocate into the nucleus.
      In addition, such junctional plaque proteins have been shown to act as effective
      suppressors of tumorigenesis.

PMID- 9013673
TI  - ERM (ezrin/radixin/moesin) family: from cytoskeleton to signal transduction.
AB  - The ERM family consists of three closely related proteins, ezrin, radixin, and
      moesin, that are thought to work as cross-linkers between plasma membranes and
      actin-based cytoskeletons. Recent analyses of the structure and functions of ERM
      proteins have revealed that these molecules are involved not only in cytoskeletal
      organization but also in signal transduction. Furthermore, identification of the
      neurofibromatosis type 2 tumour suppressor, which shows striking sequence
      similarity to ERM proteins, has increased interest in this family.

PMID- 9013674
TI  - Microtubule structure and dynamics.
AB  - The study of microtubules always manages to surprise and fascinate us, and it has
      done so yet again over the past year as significant progress has been made in the
      areas of microtubule nucleation, growth and structural polarity. Microtubule
      nucleation has been the subject of publications that show the involvement of
      gamma-tubulin-containing complexes as nucleating templates in the microtubule
      organizing centre. It is unclear how this nucleation is compatible with
      microtubule growth, which appears to take place by an unusual, and perhaps
      unique, process involving sheet-like extensions that continuously close into
      tubes as growth proceeds. The related, and longstanding, problem is that of the
      relationship between tubulin dimer structure and microtubule polarity. This
      problem appears to be solved. A number of approaches have converged to suggest
      that the tubulin dimer is organized with beta-tubulin pointing towards the
      microtubule fast-growing plus end and with alpha-tubulin towards the minus end.
      Specific decoration with kinesin monomers shows that all microtubules examined to
      date are basically organized as B-lattices.

PMID- 9013675
TI  - Actin and cell pathogenesis.
AB  - The bacterial pathogens Listeria monocytogenes and Shigella flexneri recruit host
      factors that enable them to use actin polymerization as the driving force to
      facilitate their spread into neighbouring cells. It is now becoming clear that
      other pathogens, including viruses, have developed a number of different
      strategies to use the actin cytoskeleton of the host to their advantage during
      the infection process.

PMID- 9013676
TI  - Intermediate filaments and cytoplasmic networking: new connections and more
      functions.
AB  - Recent research highlights the roles of cytoskeletal intermediate filaments (IFs)
      and their interactions with both the cell surface and other cytoskeletal systems
      in maintaining cellular integrity and the mechanical properties of cytoplasm.
      This has been demonstrated by analyses of mutations in IF-associated proteins
      (IFAPs) that are involved in connecting IFs to cell surface junctions. New data
      also point to the role of IFAPs as molecular 'nuts and bolts' in the construction
      of an integrated cytoplasmic architecture. This is highlighted by the initial
      descriptions of a family of multifunctional molecules that are capable of
      bridging IFs to other cytoskeletal elements. These findings, together with the
      development of specific peptide inhibitors capable of disassembling IF networks
      in vivo, are paving the way to the identification of new cellular functions for
      IFs and IFAPs.

PMID- 9013677
TI  - Molecular interactions in cell adhesion complexes.
AB  - Cell adhesions consist of multimolecular protein complexes of transmembrane
      adhesion receptors anchoring intracellular cytoskeletal structural proteins and
      signal transduction molecules. Recent advances reveal that components of cell
      adhesion complexes display multiple interactions and functions, which cooperate
      to mediate both cell adhesion and signaling. Cell-matrix and cell-cell adhesions
      can serve as both recipients and generators of signaling information, using
      hierarchical and synergistic molecular interactions regulated by aggregation,
      conformational changes, phosphorylation, and tension.

PMID- 9013678
TI  - Motors and membrane traffic.
AB  - The cytoskeleton is essential for the proper function of many components of
      secretory and endocytic pathways, and the importance both of microtubule motors
      (kinesins and dyneins) and of actin motors (myosins) in these pathways is
      becoming apparent. Recent experiments have improved our understanding of which
      members of these motor protein families are involved in membrane traffic.
      Multiple motors are probably involved in the control of the morphology and
      dynamics of many membranes, and intriguing hints about how these motors are
      coordinated are appearing.

PMID- 9013680
TI  - Cytoskeleton.

PMID- 9013679
TI  - mRNA and cytoskeletal filaments.
AB  - The localization of some mRNAs to distinct intracellular regions is achieved
      through interactions of the mRNA with cytoskeletal filaments. RNA-cytoskeletal
      interactions exist that influence the transport, anchoring and translation of
      mRNA. Recent analysis of RNA movements in living cells suggests the formation of
      RNA granules and their active transport along microtubules. The anchoring and
      translation of mRNA may be mediated by interactions with orthogonal networks of F
      actin and elongation factor 1alpha.

PMID- 9013700
TI  - The zeta isozyme of protein kinase C binds to tubulin through the pseudosubstrate
      domain.
AB  - It has been suggested that the protein kinase C zeta (zeta PKC) isoform is
      involved in mitogenic signaling in Xenopus oocytes and mammalian cells. Thus, the
      characterization of potential regulatory molecules that bind to zeta PKC is of
      great interest. We report here the identification by affinity chromatography of
      tubulin as a zeta PKC-binding protein. Further immunofluorescence and microtubule
      copolymerization studies are consistent with this interaction. It is suggested
      that tubulin binds to zeta PKC through its pseudosubstrate domain. Furthermore,
      results demonstrate that treatment of cells with nocodazole, which disrupts
      microtubule structures, severely impairs the activity of native zeta PKC,
      stressing the potential functional relevance of zeta PKC binding to tubulin.

PMID- 9013701
TI  - Regulation of NF-kappaB and HIV-1 LTR activity in mouse L cells by ultraviolet
      radiation: LTR trans-activation in a nonirradiated genome in heterokaryons.
AB  - A mouse model system for studying the effect of ultraviolet (uv) radiation on
      reporter gene expression directed by the human immunodeficiency virus type 1 long
      terminal repeat (HIV-LTR) has been developed to address the signals required for
      LTR trans-activation in cells with the reporter gene stably integrated into the
      genome. In a stable mouse L cell clone, L-15, NF-kappaB DNA binding activity
      induced by uv-C (254 nm) but not by tumor necrosis factor-alpha (TNF-alpha) or 12
      O-tetra-decanoylphorbol-13-acetate (TPA) correlated with the stimulation of HIV
      LTR-directed chloramphenicol acetyltransferase (CAT) activity; uv-C was more
      effective than uv-B (312 nm), while uv-A (365 nm) had little effect on CAT
      activity. Inducers of oxidative stress, such as H2O2 treatment up to 200 microM
      or ionizing radiation up to 20 Gy, also had little effect on CAT expression.
      Pyrrolidine dithiocarbamate (PDTC) inhibited NF-kappaB DNA binding and
      stimulation of CAT activity by uv-C in a dose-dependent manner. Unexpectedly,
      PDTC induced NF-kappaB DNA binding that was additive with the response with TNF.
      In an effort to separate uv irradiation and uv-induced DNA damage from
      transactivation of the HIV-LTR we devised a heterokaryon system. The fusion of uv
      irradiated human fibroblasts with a mouse L cell clone containing the HIV-LTR
      directed lacZ gene resulted in the activation of lacZ activity that was detected
      in heterokaryons at the single-cell level. These data suggest that uv-induced DNA
      damage in the chromosomal DNA containing the reporter gene cannot explain
      activation of the HIV-LTR. This finding demonstrates LTR trans-activation in a
      nonirradiated genome.

PMID- 9013702
TI  - The temporal relationship between protein phosphatase, ICE/CED-3 proteases,
      intracellular acidification, and DNA fragmentation in apoptosis.
AB  - Apoptosis occurs during development and tissue homeostasis, and under conditions
      of physical and chemical stress. During apoptosis, cells digest their DNA,
      decrease intracellular pH, shrink, exhibit protein phosphatase activity, and
      activate members of the ICE/CED-3 family of proteases. This protease activity is
      identified by cleavage of poly(ADP-ribose) polymerase (PARP). Phosphatase
      activity during apoptosis is observed as dephosphorylation of the retinoblastoma
      susceptibility protein (Rb). Serine/threonine phosphatase inhibitors can prevent
      dephosphorylation of Rb and apoptosis, suggesting that Rb dephosphorylation is an
      indication of a critical regulator of apoptosis. The experiments described here
      were designed to establish the temporal relationship between these events.
      Apoptosis was induced in human ML-1 cells by the topoisomerase inhibitor
      etoposide. An inhibitor of the ICE/CED-3 protease family, z-VAD
      fluoromethylketone (FMK), showed concentration-dependent protection from PARP
      cleavage, intracellular acidification, DNA digestion, early changes in membrane
      permeability, and cell shrinkage, thereby placing all of these events downstream
      of the ICE/CED-3 protease action. However, z-VAD-FMK did not prevent the
      dephosphorylation of Rb, placing this change upstream of the protease. These
      results suggest that the imbalance between protein phosphatase and kinase that is
      responsible for the dephosphorylation of Rb is also responsible for the
      activation of ICE/CED-3 proteases, which in turn is responsible for all the other
      events associated with apoptosis.

PMID- 9013703
TI  - BMP7 null mutation in mice: developmental defects in skeleton, kidney, and eye.
AB  - While generating bcl2 alpha transgenic mice, we found some F2 offspring of one of
      the transgenic lines which were very small and had closed eyes at the time of
      weaning. These pups died within 1 month after birth. In order to determine the
      molecular basis of this phenotype, we screened a genomic library of the above
      transgenic line with a transgene-specific probe and found that the Bmp7 gene, a
      member of the TGF beta superfamily, was inactivated by insertional mutagenesis
      due to transgene integration. The Bmp7 homozygous null condition in mice is a
      postnatal lethal mutation and is associated with various developmental defects:
      holes in the basisphenoid bone and the xyphoid cartilage, retarded ossification
      of bones, fused ribs and vertebrae, underdeveloped neural arches of the lumbar
      and sacral vertebrae, polydactyly of the hind limbs, a kinked tail, a reduced
      number of nephrons, polycystic kidney, lack of retinal pigmentation, and retarded
      lens development. These findings indicate that BMP7 is an important signaling
      molecule for normal development of the mammalian skeleton, kidney, and eye.
      Academic Press

PMID- 9013704
TI  - Decreased cellular retinol-binding protein expression coincides with the loss of
      retinol responsiveness in rat cervical epithelial cells.
AB  - In response to estrogen the rat cervical epithelium undergoes squamous
      metaplastic changes, progressing from a resting state through a proliferating,
      secretory stage and finally to a cornified stage before sloughing or being
      reabsorbed. The transition from a secretory to a cornified epithelium is preceded
      by a dramatic reduction in the expression of the cellular retinol binding protein
      (CRBP). The associations among retinoids (retinol and retinoic acid), CRBP
      expression, and estrogen-induced keratinocyte differentiation were explored in
      cultured cervical epithelial cells. Retinoids supported proliferation of cervical
      epithelial cells expressing basal keratins. Alone, estrogen had no effect on
      proliferation and enhanced expression of keratins characteristic of stratified
      cervical epithelial cells. When added together, estrogen prevented retinoid
      effects on proliferation, whereas retinoids prevented the estrogen-enhanced
      expression of differentiation-associated cytokeratins. When CRBP expression was
      repressed by elevating intracellular cyclic AMP levels, the ability of retinol,
      but not retinoic acid, to block estrogen-induced changes in keratin expression
      was severely compromised. These results support a critical role for CRBP in
      cervical cell responsiveness to circulating retinoids (primarily retinol). We
      hypothesize that retinol inhibits estrogen-induced keratinization of the cervical
      epithelium, and the drop in CRBP level results in transient vitamin A deficiency
      within cervical epithelial cells, permitting the orderly transition from the
      secretory to the cornified stage.

PMID- 9013705
TI  - Germ line chimeras from female ES cells.
AB  - Murine embryonic stem cells (ES cells) are pluripotent cells that can contribute
      to all tissues of developing mice including the germ line when aggregated with 8
      cell-stage embryos or injected into the blastocoel cavity of murine blastocysts.
      As well as for in vitro studies, they are used to introduce mutations into the
      murine genome, thereby producing new mutant mouse lines. All ES cell lines so far
      described that contribute to the germ line have been male. However, for many
      studies female ES cell lines may be essential. Female ES cells may be
      particularly useful for mutating genes located on the X chromosome which would
      otherwise be hemizygously lethal in males. We show here that female ES cells are
      able to form germ line chimeras and to sex convert a male host embryo.

PMID- 9013706
TI  - Modulation of the retinoic acid and retinoid X receptor signaling pathways in P19
      embryonal carcinoma cells by calreticulin.
AB  - Calreticulin is a widely expressed calcium binding protein that can bind to an
      amino acid sequence motif, KXGFFKR, which is present in the cytoplasmic domain of
      all integrin alpha-subunits. Closely related sequences, KXFFKR and KXFFRR, are
      encoded in the DNA-binding domain of all members of the steroid/thyroid/retinoid
      receptor superfamily and it has recently been demonstrated that calreticulin
      inhibits their activity both in vitro and in vivo. Here we present novel evidence
      that calreticulin can interfere directly with the retinoic acid (RARs) and
      retinoid X (RXRs) receptor pathways. Calreticulin exhibits the ability to inhibit
      DNA-binding activity of both heterodimeric RAR/RXR and homodimeric RXR complexes
      in vitro. Inhibition of RXR binding to DNA is achieved with a concentration of
      calreticulin that is approximately fourfold lower than that required for
      inhibition of RAR/RXR binding to a cognate binding site. Coprecipitation
      experiments suggest a direct protein:protein interaction between calreticulin and
      retinoid receptors. Stable overexpression of calreticulin in P19 embryonal
      carcinoma cells significantly decreases the rapid activation of the endogenous RA
      responsive RARbeta gene, abrogates the ability of endogenous RAR/RXR complexes to
      bind to DNA, and inhibits the emergence of the RA-induced differentiated
      phenotype. These data demonstrate that calreticulin can interfere with the two
      distinct retinoid signaling pathways through a mechanism likely involving direct
      protein:protein interactions and that disruption of the retinoid signal alters
      biological processes in vivo.

PMID- 9013707
TI  - The p53-regulated cyclin G gene promotes cell growth: p53 downstream effectors
      cyclin G and Gadd45 exert different effects on cisplatin chemosensitivity.
AB  - Among the p53-regulated genes that have been identified thus far, cyclin G is a
      relatively recent one. We conducted a series of experiments aimed at elucidating
      cyclin G function. Ectopic overexpression of cyclin G in human RKO colon
      carcinoma cells accelerated cell growth. Transfection of normal human fibroblasts
      with the cyclin G expression vector promoted clonal expansion. Cyclin G immune
      complexes isolated from the transfected cells exhibited appreciable levels of
      cyclin-dependent kinase activity, as evidenced using histone H1 as a substrate.
      The retinoblastoma protein, pRb, was detectable in cyclin G immune complexes,
      raising the possibility that Rb may be one mediator of cyclin G action. Cyclin G
      overexpressing cells were more sensitive to cisplatin cytotoxicity than the
      parent cells, probably because cyclin G overexpression overrides cell cycle
      checkpoint(s). Overexpression of another p53-regulated gene, GADD45, by contrast,
      protected cells from cisplatin killing. These findings suggest that different
      downstream effectors of the p53 pathway may exert different effects on cellular
      survival after treatment with cancer chemotherapy drugs such as cisplatin.

PMID- 9013708
TI  - Growth, differentiation, and death of retinoic acid-treated human acute
      promyelocytic leukemia NB4 cells.
AB  - Published reports vary markedly on some characteristics of retinoic acid (RA)
      effects on cell growth and differentiation of the human acute promyelocytic
      leukemia cell line NB4. We explored possible reasons for this variability and
      found that the initial cell density of the experimental culture and the stage of
      growth of the cells used to inoculate experimental cultures were critical
      parameters for obtaining reproducible growth and differentiation responses of NB4
      cells. Thus, the time to reach 50% differentiation in the presence of 1 microM RA
      and various initial concentrations of cells was 1.9 days with 2 x 10(6) cells/ml,
      3.5 days with 2 x 10(5) cells/ml, and 4.7 days with 2 x 10(4) cells/ml. With an
      initial concentration of 2 x 10(5) cells/ml we saw time- and dose-dependent
      differentiation with RA concentrations >250 nM. However, in the presence of 25
      250 nM RA, differentiation reached a maximum of about 20% on either Day 1 or Day
      2 and then declined with time. The catabolism of RA appeared to be responsible
      for the decline in differentiation. In addition, large decreases in viability
      occurred after NB4 cultures, growing without or with RA, reached a density of
      only 1 x 10(6) cells/ml. The decreases in viability were greater at intermediate
      concentrations of RA with a nadir at about 100 nM. Loss of viability was
      associated with DNA fragmentation and changes in morphology typical of apoptosis
      and necrosis. The loss of viability occurring in control cultures necessitates
      caution when these cultures are used to seed experimental cultures.

PMID- 9013709
TI  - Gene transfection of mouse primordial germ cells in vitro and analysis of their
      survival and growth control.
AB  - We evaluated electroporation, liposome-mediated transfection, and the calcium
      phosphate (CaPO4) coprecipitation method for gene transfection of mouse
      primordial germ cells (PGCs) in culture as a prelude to the investigation of
      molecular mechanisms of the germ cell development. We found that electroporation
      severely damaged PGCs, and the efficiency of liposome-mediated transfection was
      very low. In contrast, using the CaPO4 coprecipitation method, 18% of PGCs
      transfected with plasmid pSV-LT expressed simian virus 40 large tumor antigen (SV
      40 T-Ag) transiently. However, we did not detect any effects on the proliferation
      and survival of PGCs obtained from the embryonic gonads at 11.5 days postcoitum
      (d.p.c.) during 2 days of culture after the transfection. PGCs isolated from the
      11.5-d.p.c. gonads change from spread- to round-shape and exhibit growth arrest
      during a few days of culture, and these rounded PGCs quickly disappear from the
      culture. We found that the transfection and expression of Bcl-XL or adenovirus
      type 2 E1B 19,000-molecular-weight protein (E1B 19K) significantly promoted the
      survival of PGCs and retarded the disappearance of rounded PGCs from the culture
      system. These results suggest that the Bcl-XL or E1B 19K can prevent the
      apoptosis of PGCs and inhibit the cell death of the rounded PGCs in culture.

PMID- 9013710
TI  - Inhibition of protein dephosphorylation results in the accumulation of splicing
      snRNPs and coiled bodies within the nucleolus.
AB  - Coiled bodies are conserved subnuclear organelles that contain splicing snRNPs, a
      subset of nucleolar antigens, and the autoantigen p80 coilin. Most nuclei contain
      one to five nucleoplasmic coiled bodies, often with one or more located at the
      nucleolar periphery. Here we show that exposure of mammalian cells to low levels
      of the specific Ser/Thr protein phosphatase inhibitor, okadaic acid, results in
      the accumulation of p80 coilin and splicing snRNPs within nucleoli. Mutation of a
      single serine residue in p80 coilin to aspartate (S202D) also causes coiled
      bodies and splicing snRNPs to localize within nucleoli when the mutant is
      transiently transfected and expressed in HeLa cells. Neither okadaic acid nor the
      S202D coilin mutant causes nucleolar accumulation of serine-arginine-domain
      proteins. These data indicate that protein dephosphorylation is required to allow
      normal formation of nucleoplasmic coiled bodies and point to p80 coilin as a
      substrate whose phosphorylation state may regulate snRNP-nucleolar interactions.
      The data are consistent with a trafficking mechanism whereby splicing snRNPs
      cycle through the nucleolus.

PMID- 9013711
TI  - Ion selectivity in the Chlamydomonas reinhardtii flagellar regeneration system.
AB  - Extracellular Ca2+ mediates the cellular and molecular responses to cell
      stimulation of Chlamydomonas reinhardtii. Extracellular Ca2+ concentrations
      ([Ca2+]e) must exceed certain threshold values to support flagellar excision by
      acid shock and to stimulate flagellar outgrowth following mechanical shear of the
      flagella. Also, the magnitude and duration of flagellar RNA accumulations
      following acid shock or mechanical shear increase with increasing [Ca2+]e. To
      better understand the role of Ca2+ in flagellar excision, RNA induction, and
      outgrowth, we have performed a survey of the ion selectivity of each of these
      responses to acid shock. We found that flagellar excision in vivo following acid
      shock was supported by Sr2+ and Ca2+, but no other ion tested. LaCl3 and neomycin
      prevented flagellar excision following acid shock of cells in Ca2+- or Sr2+
      containing buffer. Sr2+ addition to detergent-permeabilized cell models, however,
      failed to elicit flagellar excision in vitro. Cells failed to regrow flagella
      following flagellar excision in Sr2+-containing buffer unless exogenous Ca2+ was
      added. Flagellar RNA accumulations of lower magnitude and shorter duration were
      measured in cells acid-shocked in Sr2+-containing buffer than in Ca2+-containing
      buffer. These results demonstrate that a Sr2+ influx can evoke flagellar excision
      following acid shock, but cannot directly activate the machinery for flagellar
      excision, suggesting that a Sr2+ influx induces excision by stimulating an
      intracellular Ca2+ release. Furthermore, they suggest that flagellar outgrowth
      and normal flagellar RNA induction have a strict requirement for Ca2+, which is
      not satisfied by the proposed intracellular Ca2+ release.

PMID- 9013712
TI  - Mutations affecting chromatid separation in Drosophila: the fizzy metaphase
      arrest persists in pimples fizzy and fizzy three rows double mutants.
AB  - Mutations in the Drosophila genes three rows (thr), fizzy (fzy), and pimples
      (pim) block chromosome segregation in mitosis. fzy mutations also block cyclin
      degradation and affected cells become permanently arrested in metaphase.
      Mutations in pim and thr prevent chromatid separation but proteolysis of mitotic
      cyclins occurs normally and cells leave mitosis. Since it has been shown that
      active cdc2 is required to maintain the arrest seen in fzy embryos we wished to
      determine if pim+ and thr+ were also required. By constructing double-mutant
      combinations of the three genes we have established that the fzy arrest persists
      in the absence of either pim or thr and that there is no synergistic interaction
      between pim and thr.

PMID- 9013713
TI  - Fibronectin distribution in human bone marrow stroma: matrix assembly and tumor
      cell adhesion via alpha5 beta1 integrin.
AB  - Tumor cell interactions with fibronectin (FN) are important for the development
      of secondary tumors inside the bone marrow stroma. We studied and compared the in
      situ distribution of FN in paraffin-embedded human bone marrow sections and
      investigated the in vitro regulation of FN assemblage by bone marrow stromal
      cells (BMSC). Finally, the role of FN in the interaction of BMSC with tumor cells
      was studied. Fine elongated FN-positive cell extensions, probably of stromal cell
      origin, were observed as well as a limited amount of extracellular FN deposits in
      connective tissues around capillaries and sinusoids. In vitro studies, using the
      confocal laser scanning microscope, showed that BMSC produced a high amount of FN
      with a characteristic extracellular matrix formation in an extensive network. FN
      matrix formation was predominantly detected at contact sites between cultured
      BMSC. In in vitro cultures with low cell concentrations and in vivo with a
      limited number of stromal cell contacts only limited matrix was found. From
      previous studies it is known that the alpha5 beta1 integrin is involved in the
      regulation of FN assembly. Here the role of the alpha5-subunit of this integrin
      was investigated. By using two different monoclonal antibodies (mAb) against the
      alpha5-subunit (2H6 and mAb16) the assembly of endogenous FN was completely
      blocked, indicating that these antibodies are directed against the active
      epitope. Another mAb (mAb11) against the alpha5-subunit did not affect the FN
      assemblage. Codistribution analysis of alpha5-subunits, alpha v-subunits, actin,
      and FN demonstrated that the alpha5 beta1 integrin is associated with FN and not
      with intracellular actin. Integrins alpha(v) beta1, alpha(v) beta3, and alpha(v)
      beta5, also ligands of FN, did not colocalize with FN. Codistribution of alpha v
      with the terminal ends of actin and not with FN indicates that alpha(v)-subunits
      are mainly directed to vitronectin rather than to FN. The dominant role of alpha5
      beta1 in FN interaction is underlined by effective blocking of tumor cell
      adhesion with BMSC using anti-alpha5, anti-beta1, and anti-FN antibodies. These
      results emphasize the important role of alpha5 integrin subunit in FN matrix
      assembly in human BMSC and an exclusive role of alpha5 beta1 in the anchorage and
      regulation of FN-mediated adhesion processes in the bone marrow.

PMID- 9013714
TI  - Dominant suppression of lymphocyte apoptosis by hepatoma cells.
AB  - Suppression of apoptosis appears to contribute to the development of various
      diseases, including autoimmune disorders and cancer. Numerous genes that encode
      activators and suppressors of apoptosis have been identified; however, such genes
      have not been shown to be expressed in all cell types. Furthermore, the
      sensitivity of different cell types to induction of apoptosis varies widely. We
      have employed a genetic approach using somatic cell hybridization to determine if
      apoptosis is a dominant or a recessive process in cells. These studies have
      utilized cell fusion partners with differing sensitivity to induction of
      apoptosis. The apoptosis-sensitive cells chosen were BW5147 murine thymoma cells.
      These cells readily undergo apoptosis in response to glucocorticoids and calcium
      ionophore. The resistant fusion partners were HTC rat hepatoma cells, which
      possess an intact glucocorticoid signal transduction pathway but are resistant to
      induction of apoptosis by either agent. Neither cell type expresses detectable
      Bcl-2 protein. Heterokaryons were identified by their retention of fluorescent
      cytosolic dyes and by nuclear morphology and cell size. The three types of
      heterokaryons observed were intratypic HTC/HTC and BW5147/BW5147 heterokaryons
      and intertypic BW5147/HTC heterokaryons. Glucocorticoid receptor was shown by
      immunohistochemistry to undergo hormone-dependent translocation to all nuclei in
      intertypic heterokaryons. BW5147/BW5147 heterokaryons die after treatment with
      glucocorticoid and calcium ionophore, whereas both HTC/ HTC and BW5147/HTC
      hybrids survive. The presence of multiple BW5147 cells fused to a single HTC cell
      did not affect this outcome. This demonstrates that HTC cells are able to
      dominantly suppress apoptosis in all BW5147/HTC heterokaryons. Thus, HTC cells
      contain activities that can suppress apoptosis in lymphocytes.

PMID- 9013716
TI  - Developmental and cell-type-specific expression of cell surface heparan sulfate
      proteoglycans in the rat heart.
AB  - The expression of cell surface heparan sulfate proteoglycans in rat heart was
      investigated by Northern blot analysis with specific cDNA probes. In adult heart
      syndecan-3 and glypican mRNAs were abundantly expressed. Lower levels of syndecan
      2 mRNA and very low levels of syndecan-1 mRNA were also detected. Analysis of RNA
      isolated from hearts of rats of various ages revealed that syndecan-3 and
      glypican mRNAs levels increased dramatically at birth, and continued to be
      expressed at high levels in adult animals. To determine which of these
      proteoglycans was expressed in cardiomyocytes, primary cultures of cardiomyocytes
      and nonmyocytes isolated from neonatal rat hearts were analyzed for proteoglycan
      expression. Glypican mRNA was localized almost exclusively to cardiomyocytes.
      Syndecan-3 mRNA was not detected in myocytes, but was detected in the nonmyocyte
      cells. Biochemical characterization of cardiomyocyte glypican revealed that it
      was a phosphatidylinositol-anchored heparan sulfate proteoglycan. Results of
      immunofluorescent staining of rat hearts with anti-glypican antibodies were
      consistent with the Northern blot data, and localized glypican to the lateral
      regions of myocyte plasma membrane that contact the basement membrane, as well as
      sites of myocyte adhesion junctions. At the latter site glypican colocalized with
      vinculin. Visualization of basic fibroblast growth factor binding sites by means
      of a tissue slice overlay assay also revealed colocalization with glypican. These
      results demonstrate developmental and cell-type-specific expression of membrane
      heparan sulfate proteoglycans in the heart. They also show that glypican is a
      major heparan sulfate proteoglycan expressed on the cardiomyocyte plasma
      membrane.

PMID- 9013715
TI  - Domain-specific disassembly and reassembly of nuclear membranes during mitosis.
AB  - The nuclear envelope contains three distinct membrane domains, the outer
      membrane, the inner membrane, and the pore membrane, that reversibly vesiculate
      in mitosis. We previously suggested from single-labeling immunofluorescence
      microscopy analysis of mitotic cells in culture that mitotic vesiculation of the
      nuclear membranes may proceed in a domain-specific manner (Chaudhary and
      Courvalin, J. Cell. Biol. 122, 295-306, 1993). In the present study, we add
      biochemical support to this hypothesis by sorting domain-specific mitotic
      vesicles. Antibodies directed against the lamin B receptor, a marker of the inner
      membrane, and glycoprotein gp210, a marker of the pore membrane, were used to
      isolate by affinity two populations of mitotic vesicles that were selectively
      enriched in each of these markers. These two vesicle populations were of
      different size distribution; the pore membrane-derived vesicles were smaller (80%
      being < or = 200 nm) than the inner membrane-derived vesicles (80% > or = 200
      nm). Double-labeling immunofluorescence microscopy analysis of mitotic cells in
      culture showed that the time course and topology of disassembly and reassembly of
      inner and pore membrane domains were different, confirming that domain-specific
      vesicles are generated during mitosis. In these studies, protein
      LAP2/thymopoietin beta, another marker of the inner nuclear membrane, was
      segregating as lamin B receptor, suggesting that both proteins were contained in
      the same mitotic vesicles.

PMID- 9013717
TI  - Involvement of heparan sulfate proteoglycans in the binding step for phagocytosis
      of latex beads by Chinese hamster ovary cells.
AB  - Chinese hamster ovary (CHO) K1 cells, typical nonprofessional phagocytes,
      exhibited intense phagocytosis of latex beads when incubated under serum-free
      conditions. Under the serum-free conditions, the recognition mechanism of latex
      beads by cells was investigated. Exogenous heparin and heparan sulfate but not
      chondroitin sulfate effectively inhibited the binding of latex beads to cells.
      The binding of latex beads to cells was also inhibited by treatment of cells with
      heparitinase more effectively than by treatment of cells with chondroitinase.
      Furthermore, CHO mutant cells defective in biosyntheses of both heparan sulfate
      and chondroitin sulfate proteoglycans almost completely lacked binding activity
      of latex beads. Another mutant, which is deficient in heparan sulfate
      proteoglycans but rather overproduces chondroitin sulfate proteoglycans, also
      showed lower binding activity, compared with wild-type cells. Coculture of these
      proteoglycan-less mutants and the wild-type cells did not restore the binding
      activity of the mutant cells, suggesting that membrane-bound rather than
      secretory proteoglycans were responsible for the binding of latex beads. These
      results indicated that heparan sulfate proteoglycans at the cell surface were
      involved in the binding step for phagocytosis of latex beads by CHO cells.

PMID- 9013718
TI  - Bordetella bronchiseptica dermonecrotizing toxin, which activates a small GTP
      binding protein rho, induces membrane organelle proliferation and caveolae
      formation.
AB  - We recently demonstrated that Bordetella bronchiseptica dermonecrotizing toxin
      (DNT) modifies a small GTP-binding protein rho and causes assembly of actin
      stress fibers and focal adhesions in MC3T3-E1 cells, indicating that DNT
      activates the function of rho protein (Horiguchi et al., 1995, J. Cell Sci. 108,
      3243-3251). In this study, we examined by electron microscopy ultrastructural
      changes in DNT-treated MC3T3-E1 cells under conditions in which DNT elicited the
      above morphological changes. We found that DNT induced proliferation of
      cytoplasmic membrane organelles, such as Golgi apparatus, smooth and rough
      endoplasmic reticulum, and mitochondria, and formation of plasmalemmal caveolae.
      Therefore we examined also the effect of Clostridium botulinum C3 exoenzyme (C3),
      which has been known to ADP-ribosylate and inactivate rho protein, and found that
      C3 exoenzyme inhibited the development of membrane organelles in the MC3T3-E1
      cells. These findings show that proliferation of membrane organelles and caveolae
      formation are controlled by the function of rho, which is the target of DNT
      action.

PMID- 9013719
TI  - Rab4 associates with the actin terminal web in developing rat pancreatic acinar
      cells.
AB  - Rab4 is a small GTP-binding protein that has been implicated in the regulation of
      membrane traffic and recycling of transferrin receptors and GLUT4 transporters
      along the endocytic pathway. Here we present data that suggest a novel and very
      different role for rab4 during development in the rat exocrine pancreas. On
      immunoblots of pancreatic homogenates, a dramatic increase in rab4 expression
      occurred over the first 40 h after birth, concomitant with the time of
      acquisition of stimulus-secretion coupling. Following high-speed centrifugation
      of postnuclear supernatants prepared from 1-day neonatal pancreatic homogenates,
      rab4 partitioned into a Triton X-100 insoluble particulate fraction and was
      partially solubilized upon extraction with 0.1 M Na2CO3, pH 11.5, or 1 M KCl,
      suggesting that rab4 was not an integral membrane protein. This was confirmed by
      Triton X-114 extractions of post-nuclear supernatants showing that rab4
      partitioned into the aqueous phase of Triton X-114, which is indicative of a lack
      of isoprenylation. Confocal and electron microscopic immunocytochemistry revealed
      that rab4 colocalized with the actin terminal web and microvilli in the apical
      region of the exocrine acinar cells. In view of these findings, we propose that
      rab4 is involved in the maturation of the regulated secretory pathway in
      pancreatic acinar cells through an interaction with the apical actin
      cytoskeleton.

PMID- 9013720
TI  - Competence for nuclear replication and the NOR-chromosomes of Allium cepa L.
AB  - Autotetraploid (4n = 32) cells were induced in Allium cepa L. root meristems by
      successively treating with a multipolarizing agent in anaphase (carbetamide) and
      an inhibitor of cell plate formation in telophase (caffeine). This treatment
      produced cells with their 32 chromosomes distributed in more than two nuclei.
      During G1, one of the nuclei in the resulting trinucleate cells had a DNA content
      which was equivalent to an average of 16 chromosomes, while the other 16
      chromosomes were randomly distributed in two aneuploid nuclei. In the set of 16
      chromosomes forming the onion diploid complement, there are 4 NOR-chromosomes and
      5 chromosomes carrying DNA domains providing a nucleus with the competence to
      replicate, as previously shown. Expected probabilities derived from the different
      possible models for cosegregation of both kinds of chromosomes in the two
      aneuploid nuclei of the trinucleate cells were estimated by a computer
      simulation. These expected values were compared with the recorded frequencies of
      aneuploid nuclei which were able to organize a nucleolus and to respond to
      inducers of replication. The present data are compatible with the existence of
      sequences providing a nucleus with the competence to replicate in three out of
      the four NOR-bearing chromosomes, as well as in two other chromosomes of this
      diploid complement. The scarcity of chromosomes bearing early origins able to
      initiate replication in a nucleus is a striking feature of this huge onion
      genome.

PMID- 9013721
TI  - Structural and functional analysis of the nucleolus of the fission yeast
      Schizosaccharomyces pombe.
AB  - Yeasts are an attractive model for the study of ribosome synthesis. However, our
      understanding of the relationship between the structure and function of the yeast
      nucleolus, in which preribosomal particles are synthesized, requires further
      investigations using microscopic approaches and in situ molecular biology.
      Combining cryofixation and cryosubstitution of Schizosaccharomyces pombe, we
      could identify morphologically distinct substructures in the nucleolus similar to
      the components of nucleoli of higher eukaryotes such as the fibrillar centers
      (FCs), the dense fibrillar component (DFC) and the granular component (GC). We
      complemented this morphological study by performing in situ hybridization and
      immunocytochemistry at the electron microscopy level. Using a probe complementary
      to the entire rRNA transcription unit of S. pombe, we detected rDNA at the
      periphery of the FCs, while immunocytochemistry with antibodies specific for the
      RNA polymerase I and the gar1 protein provided evidence that transcription and
      early steps of maturation take place in the DFC that extends throughout the
      nucleolus. We also present evidence that preribosomal subunits may be exported
      along tracks to the cytoplasm through all of the pores of the nuclear envelope
      and not just those in the portion of the envelope close to the nucleolus.

PMID- 9013722
TI  - Cytokine regulation of mesothelial cell proliferation in vitro and in vivo.
AB  - Previous studies have demonstrated mitogenic effects of several mediators on
      mesothelial cells in vitro, but their effects in vivo have not been investigated.
      The aim of this study was to examine the effects of various cytokines on normal
      mesothelial cell proliferation in vitro and in vivo and correlate the findings in
      both assay systems. In vitro proliferation was assessed using a technique based
      on the uptake and subsequent release of methylene blue. Autoradiographic methods
      were applied in a murine model to assess mitogenic activity of these factors on
      mesothelium in vivo. In vitro data demonstrated a dose-dependent increase in
      human mesothelial cell proliferation by all mediators examined: at optimal
      concentrations, proliferation was enhanced between 26.53 +/- 3.77% standard
      deviation (SD), p < 0.001 for fibroblast growth factor-2 (FGF-2) and 114.58 +/-
      6.97%, p < 0.001 for platelet-derived growth factor-AB (PDGF-AB) above control
      medium. In vivo, DNA synthesis in mesothelial cells was stimulated by FGF-2
      (29.52 +/- 5.85% labeled cells, compared with 7.04 +/- 4.36% for control medium;
      p < 0.001), tumor necrosis factor-alpha (TNF-alpha; 13.14 +/- 4.55% compared with
      7.23 +/- 2.85; p < 0.005) and PDGF-BB (11.53 +/- 4.74% compared with 4.67 +/-
      3.48%; p < 0.005). Transforming growth factor-beta1 (TGF-beta1) and epidermal
      growth factor (EGF) had no effect on DNA synthesis in mesothelial cells in vivo.
      It is concluded that FGF2, TNF-alpha, and PDGF stimulate mesothelial cell
      proliferation in vitro and in vivo, whereas TGF-beta1 and EGF only had a
      mitogenic effect in vitro at the concentrations examined. The mitogenic potency
      of the different PDGF isoforms in vitro was consistent with PDGF-alpha and beta
      receptor expression.

PMID- 9013723
TI  - Protein phosphatases control MAP kinase activation and microtubule organization
      during rat oocyte maturation.
AB  - Mitogen-activated protein kinase (MAP) is involved in many signal transduction
      pathways and is activated during meiotic maturation in various species. In this
      study, we used the rat oocyte to identify some of the control mechanisms involved
      in MAP kinase activation which is triggered at resumption of meiosis. We examined
      the respective contribution of this kinase and maturation promoting factor (MPF),
      or cdc2 kinase, in the regulation of microtubule behavior and in the
      reorganization of chromatin during meiotic maturation. We found that the
      resumption of meiotic division in rat oocytes coincided with the activation of
      MPF and was followed 3 h later by the activation of MAP kinase. The activation of
      the two kinases also occurred in oocytes undergoing maturation in the presence of
      the protein phosphatase inhibitor okadaic acid (OA). However, the activation of
      cdc2 kinase was only partial, whereas activation of MAP kinase was accelerated
      and began 1 h after the resumption of meiosis, i.e. 2 h earlier than in control
      oocytes. We also showed that protein synthesis was required to activate MAP
      kinase, but not cdc2 kinase. However, once MAP kinase was activated, ongoing
      protein synthesis was not necessary to maintain its activity. These results
      suggest that a negative regulation of MAP kinase slows down its activation at the
      resumption of meiosis, mediated through the level of phosphatase activity.
      Moreover, MAP kinase activation requires protein synthesis, even upon phosphatase
      inactivation by OA, suggesting also the existence of a positive control pathway.
      We observed that during the first meiotic M-phase, the spindle did not form
      immediately after cdc2 kinase activation, but that its formation coincided with
      the appearance of MAP kinase activity. However, earlier activation of MAP kinase
      by treatment with OA did not lead to premature spindle formation, but instead a
      large aster formed consisting of long microtubules radiating from the condensed
      chromatin. In OA-treated oocytes, spindles did not form and an interphase network
      of microtubule developed with time. Thus, MAP kinase is unable to substitute for
      MPF under these conditions, its activity alone being insufficient to maintain the
      progression through meiotic maturation.

PMID- 9013724
TI  - Histone H1(0) expression is restricted to progenitor cells during human
      hematopoiesis.
AB  - The histone H1(0) accumulates in cells with little or no proliferative activity
      during the terminal phase of differentiation in adult tissues. The hematopoietic
      cell system is an interesting in vivo model to study the relationship between
      H1(0) and both the proliferative capacity and differentiation state of cells.
      Using immunofluorescence techniques, we have analyzed the distribution of histone
      H1(0) during human hematopoietic differentiation, in normal bone marrow cells and
      in cell lines representative of cells blocked at early stages of differentiation.
      In enriched bone marrow cell suspensions, H1(0) was not expressed in any cell
      population highly engaged into a differentiation pathway. However, more than 50%
      of cells from blastic population (CD34-positive cells) were expressing H1(0),
      whereas only 5% of CD34-negative cell population expressed H1(0). We show that
      H1(0) was also detected in almost all the cell lines studied. These results
      indicate that histone H1(0) is expressed in immature cells which, although
      committed, still retain several differentiation potentialities. For normal human
      hematopoiesis, cells expressing H1(0) belong to a population of cells that are
      largely quiescent, although having a high proliferative capacity. H1(0) is no
      longer present in terminally differentiating or differentiated cells with limited
      or no proliferative potential. Thus, we suggest that H1(0) accumulates in cells
      with little or no proliferative activity but which are able to resume cell
      proliferation if required. These results are in keeping with the hypothesis that
      H1(0) contributes to stabilize a chromatin structure in cells for which integrity
      and/or longevity are essential.

PMID- 9013725
TI  - Subcellular localization and expression pattern of the neurofibromatosis type 2
      protein merlin/schwannomin.
AB  - To elucidate the physiological function of the neurofibromatosis type 2 (NF2)
      tumor suppressor protein merlin/schwannomin, we studied the expression pattern
      and subcellular localization in human fibroblasts by Western blot analyses and
      immunofluorescence using a polyclonal antibody raised against the C-terminus of
      merlin. Three of the six merlin isoforms identified in this study (75 kDa, 58
      kDa, 45 kDa) have been reported earlier and can be explained by alternative
      splicing. In addition, we detected higher molecular weight bands of about 110
      kDa, 100 kDa and 84 kDa. Although the merlin bands of 100 kDa and 110 kDa may
      represent homo- or heterodimers, oligomerization due to formation of disulfide
      bonds was excluded. Furthermore, the isoforms of 84 kDa and 58 kDa were
      quantitatively extractable in Lubrol WX, indicating a localization in or close to
      the plasma membrane. The 45 kDa band, however, was not soluble in Lubrol WX
      compatible with a localization of this NF2 isoform in the endoplasmic reticulum.
      Applying confocal laser scanning microscopy, merlin was shown to be located in
      four subcellular compartments: (i) perinuclear in a compartment resembling
      endoplasmic reticulum, (ii) in ruffling membranes and at the leading edges, (iii)
      in filopodia, and (iv) at cell/substrate adhesion points. Codistribution of
      merlin and F-actin filaments was found in filopodia, ruffling membranes and at
      the insertion points of stress fibers at cell/substrate adhesion junctions as
      shown by phalloidin-rhodamine staining. Double immunofluorescence analyses of
      merlin and moesin revealed a colocalization in filopodia and ruffling membranes.
      The localization of merlin in the actin-rich cortical cytoskeleton corresponds to
      the ezrin-radixin-moesin family of proteins suggesting the NF2 protein to
      contribute to the regulation of cell growth by interaction with cytoskeleton
      associated proteins.

PMID- 9013726
TI  - The apical sorting of lactase-phlorizin hydrolase implicates sorting sequences
      found in the mature domain.
AB  - Polarized transport of proteins is contingent on the presence of specific protein
      structures or motifs that function as sorting signals. Our model protein to
      analyze and to identify such signals is that of lactase-phlorizin hydrolase
      (LPH), a strictly polarized brush border membrane protein of small intestinal
      epithelial cells. It is synthesized as a large pro-LPH precursor molecule, which
      is proteolytically processed to yield the mature brush border enzyme (LPHbeta).
      Pro-LPH as well as LPHbeta are correctly sorted to the brush border membrane. In
      this paper we examine the location of putative sorting signals in the pro-LPH
      molecule. Expression of a cDNA encoding the LPHbeta mature form in the absence of
      the LPHalpha species in Madin-Darby canine kidney (MDCK) cells reveal an LPHbeta
      molecule that is not as transport-competent as wild type pro-LPH. The proportion
      of complex glycosylated LPHbeta constitutes not more than 10% of the total
      synthesized protein. This form displays a similar trypsin sensitive pattern as
      wild type intestinal LPHbeta suggesting comparable folding patterns of the two
      species. Complex glycosylated LPHbeta is sorted to the apical membrane more
      efficiently than wild type pro-LPH. We conclude that the apical sorting signals
      for pro-LPH are exclusively found in the LPHbeta mature domain.

PMID- 9013727
TI  - Influence of N-methylformamide on the intracellular transport of doxorubicin.
AB  - The polar solvent N-methylformamide proved to be capable of enhancing the
      cytotoxic potential of various antitumoral compounds, both in vitro and in vivo.
      In many cases, this ability depended on the sequence of treatment, and the
      enhancement of the cytotoxic effect occurred only when N-methylformamide
      administration succeeded anticancer drug treatment. The results obtained in the
      present study indicate that N-methylformamide interferes with the mechanisms of
      intracellular transport and efflux of the antitumoral drug doxorubicin. In
      particular, laser scanning confocal microscopy observations performed on melanoma
      cells (M14) after N-methylformamide administration revealed evident alterations
      of the microtubular network, including numerous interruptions of the
      microtubules. Moreover, when doxorubicin-treated cells were recovered in the
      presence of the polar solvent, the normal efflux of the anthracyclinic antibiotic
      appeared to be hampered, and the drug was localized mainly in well delimited
      perinuclear regions. Double staining experiments demonstrated the colocalization
      of the doxorubicin molecules and the WGA-stained regions as well as a close
      structural relationship between them and the microtubule system. These results
      indicate that N-methylformamide interferes with the doxorubicin transport
      inducing a damage in the microtubular network and the consequent persistence and
      entrapment of the drug in the regions likely occupied by the Golgi apparatus of
      tumor cells. This finding could account for the chemosensitizing properties
      exerted by N-methylformamide.

PMID- 9013728
TI  - Immunocytochemical localization of the 70 kDa peroxisomal membrane protein in
      connections between peroxisomes in rat liver: support for a reticular
      organization of peroxisomes maintained by the cytoskeleton.
AB  - Recently it has been shown that peroxisomes interact with microtubules which
      affect the structure and intracellular distribution of the organelle (Schrader,
      M., J. K. Burkhardt, E. Baumgart, G. Luers, H. Spring, A. Volkl, H. D. Fahimi:
      Interaction of microtubules with peroxisomes. Tubular and spherical peroxisomes
      in HepG2 cells and their alterations induced by microtubule-active drugs. Eur. J.
      Cell Biol. 69, 24-35 (1996)). In the present work, we have applied immunological
      techniques to study the organization of peroxisomes within the rat liver cell.
      Antibodies to a pentadecapeptide corresponding to amino acid residues 403-417 of
      the 70 kDa integral peroxisomal membrane protein (Kamijo, K., S. Taketani, S.
      Yokota, T. Osumi, T. Hashimoto: The 70-kDa peroxisomal membrane protein is a
      member of the Mdr (P-glycoprotein)-related ATP-binding protein super family. J.
      Biol. Chem. 265, 4534-4540 (1990)) were raised in rabbits and affinity purified.
      This antibody was found to be highly specific for peroxisomes as determined by
      ELISA and Western blot analysis. Immunoelectron microscopy of tissue sections
      from rat liver revealed that peroxisomal membranes were labeled with this
      antibody and, in addition, labeling was found on tubular extensions often
      connecting peroxisomes. Antibodies to alpha-tubulin were used to locate the
      microtubular system. Microtubules were often found in close connection to
      peroxisomes, suggesting interaction between peroxisomes and the cytoskeleton.
      Double-labeling experiments for the 70 kDa integral peroxisomal membrane protein
      and alpha-tubulin demonstrated that the tubular structures connecting peroxisomes
      did not colocalize with microtubules. These results suggest that peroxisomes are
      organized in reticular structures within rat liver cells and that the structure
      and localization of these reticuli may be determined by their association to the
      microtubular network.

PMID- 9013729
TI  - Expression of transferrin receptors in endothelial cells transfected by
      electroporation.
AB  - Transferrin is the primary iron-binding protein in the plasma. Transferrin
      receptors (TfR) were detected in brain and liver endothelial cells (EC); however,
      little information exists about their intracellular routes. To detect the EC
      structures involved in TfR biosynthetic and endocytotic pathways, cultured aortic
      EC were transfected with the plasmid pSR alpha containing a construct encoding
      the human TfR, to which horseradish peroxidase (HRP) was anchored as reporter
      molecule. Since EC are difficult to be transfected, we tried different
      techniques, and two forms of the plasmid (circular and linearized), of which the
      electroporation method and the linearized plasmid were the most efficient in
      producing stable cell lines. Transfected cells were selected with geneticin, and
      the expression of TfR-HRP tested by cytochemistry. The stable transformants
      preserved the general characteristics of EC. At the ultrastructural level, TfR
      HRP was associated with the nuclear envelope, rough endoplasmic reticulum, Golgi
      complex and adjacent secretory vesicles, cytoplasmic vesicles of various sizes
      (50-130 nm diameter), endosomes, plasma membrane, plasmalemmal pits, and a
      fraction of plasmalemmal vesicles. The intensity of the reaction product varied,
      suggesting a different concentration of TfR, in specific organelles. For example,
      (i) a gradient of HRP-reaction product was found within the Golgi cisternae, (ii)
      the plasmalemmal pits were more intensely stained than the adjacent plasma
      membrane, and (iii) the vesicle membrane was decorated stronger than the
      endosomal membrane (to which it fuses). A striking feature was the coexistence
      within the same EC of two vesicle populations (or subtypes): some containing TfR
      HRP, whereas others lack the receptor. Quantitative data indicated a stronger
      expression of TfR in confluent cells (approximately 8-fold higher) than in EC at
      2 days after plating; a significant decrease (approximately 9-fold) of TfR was
      found in postconfluent transfectants. Together, the data demonstrate that (i)
      after electroporation of EC, the stable lines maintain the characteristics of
      native cells; (ii) the newly synthesized TfR is located in variable concentration
      within the organelles involved in endocytosis and exocytosis, and (iii) the
      expression of TfR-HRP is particularly high in confluent cells.

PMID- 9013730
TI  - Immunocytochemical electron microscopic study and Western blot analysis of
      caldesmon and calponin in striated muscle of the fruit fly Drosophila
      melanogaster and in several muscle cell types of the earthworm Eisenia foetida.
AB  - Caldesmon and calponin are two proteins that are characteristic of vertebrate
      smooth muscle. In invertebrates, caldesmon has only been studied in some
      molluscan muscles, and no previous references to calponin have been found. The
      aim of this paper was to investigate the presence and distribution of caldesmon
      and calponin in several invertebrate muscle cell types, classified according to
      their ultrastructural pattern: transversely striated muscle (flight muscle from
      Drosophila melanogaster), obliquely striated muscle (muscular body wall and inner
      muscular layer of the pseudoheart from the earthworm Eisenia foetida), and a
      muscle of doubtful classification which seems to be intermediate between smooth
      muscle and obliquely striated muscle (outer muscular layer of the pseudoheart,
      from E. foetida), using electron microscopy immunocytochemistry and Western blot
      analysis. Immunoreactions to both caldesmon and calponin were observed in the
      outer muscular layer cells from the earthworm pseudoheart but neither in the
      transversely striated muscle of D. melanogaster nor in the obliquely striated
      muscle from the earthworm. Present findings suggest that caldesmon- and calponin
      like proteins are also present in invertebrate muscle cells, but only in those
      that are ultrastructurally similar to the vertebrate smooth muscle cells. Since
      discrepancies in the classification of some invertebrate muscles are common in
      the literature, the use of distinctive markers, such as troponin, caldesmon and
      calponin may improve our understanding of the nature and properties of many
      invertebrate muscles showing an ultrastructural pattern that does not resemble
      any of the classic muscle types.

PMID- 9013731
TI  - The OB protein (leptin) pathway--a link between adipose tissue mass and central
      neural networks.
AB  - OB protein (also known as leptin), a previously unknown protein signal, is
      secreted from adipose tissue, circulates in the blood, probably bound to a family
      of binding proteins, and acts on central neural networks that regulate ingestive
      behavior and energy balance. OB protein provides a communication link from fat
      tissue and the brain. Rapidly accumulating evidence suggests that OB protein
      appears to play a major role in the control of body fat stores through
      coordinated regulation of feeding behavior, metabolism, autonomic nervous system
      and body energy balance in rodents, primates and humans. The field has rapidly
      moved from cloning of the ob gene to demonstration of complex regulation of ob
      gene expression in adipose tissue in rats and humans, and then the demonstration
      of potent biological activity of OB protein in ob/ob, diet-induced, and lean mice
      as well as obese and lean rats but not in db/db obese mice. A significant
      milestone was our demonstration that central administration of OB protein lead to
      reductions in food intake, body weight and alterations in metabolism consistent
      with activation of the autonomic nervous system. These findings were followed by
      the identification of a central binding site for labelled OB protein in the
      choroid plexus in ob/ob, db/db and lean mice as well as lean and obese Zucker
      rats. The expression cloning of a central receptor, OB-R, from the mouse choroid
      plexus soon followed. The OB-R receptor was found to be expressed in the choroid
      plexus, the hypothalamus as well as several peripheral tissues. OB-R exists in
      multiple forms; the two major forms are a short form (with a truncated
      intracellular domain) and long form (with the complete intracellular domain). The
      long form is thought to be the form that signals and mediates the biological
      effects of OB protein. Initial in situ hybridization studies have demonstrated
      the mRNA for the long form OB-R receptor to be localized to the hypothalamus as
      well as peripheral sites. Recently, it was demonstrated that the db gene encodes
      the OB-R receptor. Evidence has been provided for a specific transport system for
      OB protein to cross the blood-brain-barrier and enter the brain of mice, rats and
      humans. The rate of transport can be decreased by high plasma concentrations of
      OB protein. Thus, reduced entry of OB protein to the brain may be one of the
      mechanisms of reduced sensitivity of the OB protein pathway in obese individuals.
      OB protein appears to also play a role in the important neuroendocrine adaptive
      responses to fasting and in the control of reproduction. Therapeutic approaches
      to the treatment of obesity based on OB protein ranging from OB protein by
      injection to OB-R receptor agonists and to upregulation of OB signalling pathways
      are under intense investigation.

PMID- 9013732
TI  - Role of the beta3-adrenoceptor in the control of leptin expression.
AB  - The inhibitory effect of beta-adrenoceptor agonists on leptin expression in brown
      and white adipose tissues is now well documented both in vivo and in vitro. It
      suggests the existence in vivo of a retroregulatory loop by which leptin inhibits
      its own expression via the sympathetic nervous system and the beta3-adrenoceptor.
      The hypothesis that the defect in beta3-adrenoceptor described in the adipose
      tissue of hereditary obese rodents can contribute to the resistance to leptin and
      to the increase in leptin expression observed in these animals is discussed.

PMID- 9013733
TI  - Regulation of ob gene expression in rodents and humans.
AB  - The discovery of the obese gene in the mouse and its conserved homologue in
      humans has led to important discoveries in energy metabolism. One of the chief
      findings was the fact that the expression of the leptin gene was regulated and
      that it, in turn, could regulate metabolism and behavior. Much of the literature
      has focused on the physiological role of leptin in driving processes as diverse
      as reproduction, starvation defence, feeding behavior or body weight, all
      dependent on expression levels of the ob gene. Here, we will describe our work,
      in which we have begun to elucidate the regulatory processes controlling obese
      gene expression.

PMID- 9013734
TI  - The loop system between neuropeptide Y and leptin in normal and obese rodents.
AB  - Over the years, the work of research laboratories in Baton Rouge (USA), Seattle
      (USA) and Geneva (Switzerland) have reached analogous conclusions regarding the
      main etiology of obesity as studied in animals: it largely lies within the brain,
      notably within the hypothalamus. The hypothalamus is indeed known to modulate
      food intake and energy partitioning, while the periphery has also been proposed
      to feed-back on the central nervous system (CNS) to provide information on the
      state of body energy stores, the two together constituting a loop system
      connecting the brain to the periphery (1,2,3). This etiologic viewpoint of a
      pivotal role of the hypothalamus in obesity syndromes has been strengthened by
      the discovery of one hypothalamic neuropeptide and one peripheral (adipose
      tissue) hormone, respectively neuropeptide Y (4), and quite particularly, leptin
      (5). As neuropeptide Y produces hyperphagia (6, 7) and as leptin produces
      hypophagia in normal animals (8,9,10), the loop system just mentioned was thought
      to comprise functional relationships, at least between these two factors. Other
      evidence also suggested that such a loop system was altered in obese animals.

PMID- 9013735
TI  - The leptin haemopoietic cytokine fold is stabilized by an intrachain disulfide
      bond.
AB  - Structure prediction algorithms have tagged leptin as the newest member of the
      haemopoietic cytokine family, a diverse class of secreted hormone-like factors
      with pleiotropic effects in immunity and haemopoietic development. While
      haemopoietic cytokines typically lack sequence similarity, they conserve a
      distinctive three-dimensional fold, a four-alpha-helix bundle structure that is
      recognized by the cognate family of haemopoietic cellular receptors. We have
      constructed a detailed molecular model of the human leptin helical fold that
      places the two cysteine residues of the leptin chain, Cys96 and Cys146, in close
      spatial proximity to each other. In this report, we present evidence that these
      cysteines are involved in an intrachain disulfide bridge that is critical for the
      structural integrity and stability of leptin. A leptin variant that is unable to
      form the disulfide link shows a reduced biological response when administered to
      leptin-deficient, ob/ob mice.

PMID- 9013736
TI  - The relationship of tissue localization, distribution and turnover to feeding
      after intraperitoneal 125I-leptin administration to ob/ob and db/db mice.
AB  - Brain and whole body localization and distribution of 125I-leptin was determined
      after intraperitoneal administration to ob/ob and db/db mice, and was compared to
      inhibition of food intake. Food intake was not significantly inhibited at3 hours
      post-injection, but was decreased significantly at 6 h (p < 0.0007) and 24 h (p <
      0.02) in ob/ob mice, times at which > 97 % of the radioactive dose was found in
      the urine. The highest concentrations of 125I-leptin at all time-points were
      found in the serum, liver and kidneys. These findings were verified by whole body
      autoradiography. Virtually no 125I-leptin was found in the CNS at later
      timepoints in either ob/ob or db/db mice. Coronal sectioning of entire brains
      from ob/ob and db/db mice revealed 125I radioactivity localized to the choroid
      plexus and in the ventricular space, but not in other CNS regions. No differences
      in localization, accumulation, or clearance of 125I-leptin in ob/ob vs. db/db
      mice were found in any of the tissues studied. The present studies demonstrate
      that the inhibitory effect of leptin on food intake in the ob/ob mouse persists
      for up to 24 hours after a single dose, despite the complete degradation and
      elimination of the labeled leptin during the first several hours after injection.

PMID- 9013737
TI  - Intracerebroventricular injection of leptin increases thermogenesis and mobilizes
      fat metabolism in ob/ob mice.
AB  - Genetically obese (ob/ob) mice display a number of metabolic alterations,
      including decreased thermogenesis, hyperphagia, hyperglycemia and increased body
      fat. A single intracerebroventricular (i.c.v.) injection of these mice with
      leptin (0.01 to 1 microg) lowered food intake and body weight within 24 h. In
      addition, i.c.v. administration of leptin increased 22 h energy expenditure while
      reducing the respiratory quotient (RQ) in a dose-dependent manner. The leptin
      induced decrease in RQ suggests a reduction in the fraction of total energy
      derived from carbohydrate oxidation and a corresponding increase in energy
      derived from fat oxidation. Our data suggest that leptin controls energy
      homeostasis through activation of receptor(s) in the central nervous system (CNS)
      that regulate both food intake and energy metabolism.

PMID- 9013738
TI  - Intraventricular leptin reduces food intake and body weight of lean rats but not
      obese Zucker rats.
AB  - The protein encoded by the obese (ob) gene, leptin, is secreted from adipose
      tissue and is proposed to act in the brain as an important regulator of food
      intake and body weight. To investigate the direct effects of leptin within the
      CNS, we injected 3.5 microg of either mouse or human leptin into the third
      ventricle (ICV) of lean Long-Evans rats or obese (fa/fa) Zucker rats, in which
      obesity results from a mutation in the leptin receptor gene. ICV administration
      of leptin reduced 4-h food intake in both deprived and non-deprived lean rats. In
      addition, repeated ICV administration produced a long-lasting reduction in body
      weight while peripheral administration of the same dose had no effect. ICV
      administration of the same dose of leptin into the third ventricle of obese
      Zucker rats did not reduce food intake. These results are consistent with the
      hypothesis that leptin has direct actions in the CNS as an afferent signal
      related to the state of energy stores in adipose tissue. Furthermore,
      insensitivity to these central effects of leptin may be an important determinant
      of obesity.

PMID- 9013739
TI  - Evidence that reduced leptin levels, but not an aberrant sequence of leptin or
      its receptor, contribute to the obesity syndrome in NON mice.
AB  - NON mice exhibit a polygenic syndrome of mild obesity which is less pronounced
      than that of the ob and db strains. Here, we have shown that the syndrome is
      accompanied by a rise in leptin mRNA levels in adipose tissue, corresponding with
      the increase in adipose tissue mass. Surprisingly, levels of the leptin protein
      in adipose tissue and serum were comparable to those of lean control animals
      (BL57/Ksj-+/+), and markedly lower than those in db/db-mice. The coding regions
      of the cDNA sequences of both leptin and the leptin receptor from NON mice were
      identical with those of the wild-type sequences. We suggested that low levels of
      leptin in adipose tissue and serum contribute to the obesity of NON mice.

PMID- 9013740
TI  - Hyperleptinemia: relationship to adiposity and insulin resistance in the
      spontaneously obese rhesus monkey.
AB  - Plasma leptin levels in normal-weight and spontaneously obese male rhesus
      monkeys, and the relationships of circulating leptin to beta-cell basal
      secretion, glucose-stimulated responsiveness and peripheral insulin sensitivity,
      were determined. Basal leptin in normal lean adult monkeys averaged 6.0 +/- 1.3
      ng/ml and in the obese monkeys averaged 22.6 +/- 2.9 ng/ml. In all monkeys,
      plasma leptin concentration was significantly related to body weight, body fat,
      fasting plasma insulin, acute insulin response to intravenous glucose, and
      peripheral insulin sensitivity but not to fasting glucose or glucose tolerance.
      Body fat and plasma insulin concentration were the best predictors of circulating
      leptin levels (R2 = 62.6%) independent of peripheral insulin sensitivity. Four of
      17 obese monkeys had plasma leptin concentrations in the normal range, a finding
      that may be related to the heterogeneity of obesity. The close association of
      plasma leptin to body fat and plasma insulin (both basal and glucose-stimulated)
      support the possibility of a role of leptin in the link between obesity and beta
      cell hypersecretion. However, the potential role of leptin in the development of
      peripheral insulin resistance, hyperglycemia and type 2 diabetes will require
      further study.

PMID- 9013741
TI  - Effects of nutritional status and aging on leptin gene expression in mice:
      importance of glucose.
AB  - The factors regulating leptin mRNA under physiological conditions have not been
      fully elucidated, although both insulin and glucose have been implicated. Since,
      in male mice, plasma glucose decreases with age without a change in body weight
      or insulin, aging mice constitute a model to examine effects of glucose
      independent of effects of insulin or body weight. Therefore, we measured leptin
      mRNA in adipose tissue of 6-, 15- and 24-month-old C57BL/6J male mice, sacrificed
      either after a 48 h fast (nutritional deprivation) or 15 min after an
      intraperitoneal injection of glucose (2 mg/g body weight) (nutritional
      stimulation). There was a significant effect of both age and nutritional status
      on leptin mRNA, correlated with effects of age and nutritional status on plasma
      glucose. Leptin mRNA correlated with body weight, plasma glucose and plasma
      insulin. After statistically removing effects of plasma glucose, the remaining
      effects of age, nutritional status, and plasma insulin on leptin mRNA were no
      longer significant. However, after statistically removing effects of plasma
      insulin, the remaining effects of age, nutritional status, and plasma glucose
      continued to be significant. When nutrition-deprived and nutrition-stimulated
      mice were analyzed separately, plasma glucose significantly correlated with
      leptin mRNA in both groups, but body weight and plasma insulin correlated with
      leptin mRNA only in nutrition-deprived mice. When mice at each age were analyzed
      separately, glucose correlated with leptin mRNA at every age, and after
      statistical removal of the effects of glucose, the remaining effects of insulin
      on leptin mRNA were no longer significant at any age. These results support the
      hypothesis that plasma glucose is important in the regulation of leptin gene
      expression.

PMID- 9013742
TI  - Regulation of leptin production in cultured mature white adipocytes.
AB  - A 96-well plate format system is described for the in vitro culture and analysis
      of leptin secretion by mature adipocytes. Cultured adipocytes secreted leptin in
      a linear fashion over a 48 h period and secretion was inhibited by actinomycin D
      treatment. Dexamethasone and insulin stimulated leptin production in vitro, with
      dexamethasone proving a more potent stimulus throughout. Culture of adipocytes
      with insulin and dexamethasone together resulted in an additive release of
      leptin, suggesting that stimulation by these factors operates via independent
      routes. Isoprenaline (1 - 1000 microM) was a potent inhibitor of leptin
      production but propanolol (3 microM) could block this inhibition. Inclusion of
      growth hormone, insulin-like growth factor 1 or tumor necrosis factor alpha did
      not affect leptin secretion by mature adipocytes.

PMID- 9013743
TI  - Difference in leptin mRNA levels between omental and subcutaneous abdominal
      adipose tissue from obese humans.
AB  - Differences in fat cell size and function among adipose tissue depots are well
      known and may be important in the pathophysiology of the metabolic and
      cardiovascular complications of obesity. Since the newly discovered adipocyte
      hormone leptin is thought to be a central factor in the regulation of energy
      homeostasis, it may be interesting to know if there are regional differences in
      leptin production. The aim of this study was to compare the level of leptin
      expression in the omental and subcutaneous abdominal adipose tissue from obese
      humans. Adipose tissue samples were collected from 25 severely obese adults (mean
      BMI: 48.9 +/- 9.7 kg/m2) undergoing vertical gastric banding. Semi-quantitative
      determination of leptin mRNA by the RT-PCR technique showed significantly lower
      leptin expression in omental compared to subcutaneous abdominal adipose tissue
      (leptin/Sp1 ratio in omental vs. subcutaneous fat: 1.53 +/- 0.89 vs. 3.02 +/-
      1.58, p < 0.01). Identical results were obtained when Northern blotting was
      applied in a subgroup. Leptin expression increased with age in omental adipose
      tissue (r = 0.42, p < 0.05), but not in subcutaneous tissue. No correlation was
      found between BMI or waist/hip ratio (WHR) and leptin expression in omental or
      subcutaneous adipose tissue. The regional difference in leptin expression was
      similar in the patients with impaired glucose tolerance/type-2 diabetes and those
      with normal glucose tolerance. In conclusion, the results of this study indicate
      that leptin expression is lower in omental than subcutaneous adipose tissue,
      possibly due to differences in fat cell size and/or sympathetic innervation.

PMID- 9013744
TI  - Purification of milligram quantities of human leptin from recombinant E. coli.
AB  - Leptin, the product of the obese (ob) gene, is a 16 kilodalton protein secreted
      from adipose tissue. Restoration of leptin to obese ob/ob mice leads to
      normalization of body weight. The effect of leptin in larger animals has not been
      explored, in part because of limited supplies of leptin. To date, the potency and
      yield of recombinant leptin purified from a variety of eukaryotic sources or from
      E. coli has been highly variable. While purification of leptin from E. coli
      inclusion bodies has afforded the greatest yield of protein, its potency is at
      least an order of magnitude lower than that of leptin secreted from E. coli or
      eukaryotic cells. The mechanistic basis of this difference in potency is not
      clear at present. The ability to purify significant quantities of highly active
      leptin will be crucial for the evaluation of leptin structure, as well as its
      function in additional animal models of obesity. We now report a facile protocol
      for the preparation of recombinant leptin using an E. coli expression system. 75
      85 milligrams of leptin with a purity of greater than 97 % was prepared from a
      liter of recombinant E. coil. The procedure can be performed in less than 48 h
      and requires no chromatography. Intraperitoneal injection of 0.1 mg/kg renatured
      leptin into ob/ob mice results in a significant reduction in food consumption.
      The potency of this material is similar to the most potent recombinant leptin
      described to date. The ability to rapidly prepare large quantities of high
      specific activity material will hasten the definition of leptin's role in non
      rodent models of obesity.

PMID- 9013745
TI  - Relationship between weight loss maintenance and changes in serum leptin levels.
AB  - Serum leptin concentrations are higher in obese humans than in lean and are
      decreased by initial weight loss. This study examined the effects of maintenance
      of weight loss on leptin concentrations and tested whether leptin concentrations
      at baseline or after initial weight loss are related to the ability to maintain a
      reduced body weight. Fifty-two overweight women [body mass index (kg/m2)
      averaging 31.3] were studied before and after a 4 month weight loss program and
      at 6 month follow-up. Subjects lost 8.1 kg over the 4 month program, and leptin
      concentrations decreased from 30.1 to 20.4 ng/ml. Initial leptin level per unit
      body mass index (r = -0.61, p < 0.0001) and weight loss during months 0 to 4 (r =
      0.39, p = 0.004) were both significantly associated with initial changes in
      leptin, and together explained 60% of the variance in change in leptin. Subjects
      who maintained their weight losses over the 6-month follow-up maintained their
      reductions in leptin levels; again, weight changes during follow-up were
      correlated with changes in serum leptin levels (r = 0.41, p = 0.003). There was
      no evidence that baseline leptin concentration (or leptin/body mass index) or the
      changes in leptin which accompanied initial weight loss were predictive of
      subsequent weight regain. Thus, changes in leptin concentration during weight
      loss track with changes in weight. However, neither baseline concentrations nor
      initial changes in leptin predict success at weight loss or maintenance.

PMID- 9013746
TI  - Dexamethasone induces an acute and sustained rise in circulating leptin levels in
      normal human subjects.
AB  - Leptin, the protein product of the ob gene, is thought to have a role in
      signalling satiety through hypothalamic pathways. Glucocorticoids are potent
      stimulators of both ob gene expression and circulating leptin levels in the rat,
      yet are powerful appetite stimulants in humans. We have investigated circulating
      leptin responses to intermediate term and acute administration of dexamethasone.
      Dexamethasone 2 mg twice daily resulted in a rapid and sustained rise in 08.00 h
      leptin levels from basal values of 1.36 +/- 0.25 to 3.58 +/- 1.72 microg/l after
      24 hours of treatment. Following placebo administration 24 h profiles confirmed a
      nocturnal rise in leptin levels with an increase of 73 +/- 37% at midnight
      compared with 0.9.00 h. After dexamethasone mean leptin levels increased by 123
      +/- 51% (p = 0.0016), with an accentuation in the diurnal variation and
      associated hyperinsulinemia. The study confirms a nocturnal rise in leptin in
      humans, and demonstrates increases in leptin in response to glucocorticoid
      administration as previously demonstrated in the rodent. The divergence between
      appetite stimulating effects of glucocorticoids despite induction of a proposed
      satiety factor suggests that regulation of leptin levels and regulation of
      appetite is multifactorial, and other neurotransmitter pathways are presumably
      involved.

PMID- 9013747
TI  - High leptin concentrations in serum of very obese children are further stimulated
      by dexamethasone.
AB  - Serum leptin concentrations and the levels of ob mRNA in adipocytes in obese
      humans are elevated. Hyperphagia and obesity are characteristics of
      hypercortisolism. We have therefore asked whether or not leptin levels were
      elevated in very obese children, and whether or not dexamethasone would increase
      leptin levels in obese children. A single dose dexamethasone suppression test was
      performed in ten obese children (5 girls, 5 boys; age 6 to 16 yrs, mean 12 +/- 1,
      median 12 yrs) to rule out hypercortisolism. Body mass index (BMI) in the ten
      children was calculated to be 27-45 kg/m2. Venous blood was sampled before
      dexamethasone was given in the evening and at 9.00 a.m. the following morning.
      Endogenous cortisol production was suppressed in all patients. Leptin levels, as
      measured by a newly developed specific radioimmunoassay, were 31.6 +/- 12.9
      microg/l, range 19.2-59.9 microg/l before dexamethasone and 39.9 +/- 16.5
      microg/l, range 26.3-80.3 microg/l after dexamethasone in the obese children
      (ANOVA, p = 0.01). Simple regression analysis revealed that serum levels
      correlated significantly with body mass index (r = 0.82, p < 0.001). Non-obese
      children (BMI < 27 kg/m2) had leptin levels between 0.1 and 33.3 microg/l, median
      2.2 microg/l (N = 713). Girls (5.5 +/- 4.6 microg/l) (N = 401) had significantly
      higher leptin levels than boys (1.7 +/- 2.1 microg/l (N = 312) (p < 0.0001). We
      conclude that 1) high serum leptin concentrations are present in obese children.
      2) A single dose of dexamethasone significantly increases the high leptin serum
      levels in these children. We hypothesize that glucocorticosteroids up-regulate
      leptin levels in the human.

PMID- 9013748
TI  - Serum immunoreactive-leptin levels are increased in patients with Cushing's
      syndrome.
AB  - Leptin, the product of the ob gene, is a recently discovered hormone secreted by
      adipocytes. Cushing's syndrome is a disease state usually associated with weight
      gain due to the accumulation of adipose tissue. In order to study the effect of
      chronic glucocorticoid excess upon serum leptin levels; in the present work, four
      patients with recently diagnosed Cushing's syndrome and a group of control
      subjects matched for age, sex and body mass index (BMI) were studied. Serum
      leptin concentrations, measured by radioimmunoassay, were assessed in samples
      taken every 60 minutes over a 24 hour period. Assessment of leptin concentrations
      over 24 hours, by means of the area under curve showed a twofold increase in
      serum leptin levels in patients with Cushing's syndrome (mean+/-SEM 54.3+/-14) in
      comparison to control subjects (29.3+/-4.4; p<0.05). In conclusion, our data show
      that leptin levels are markedly increased in Cushing's syndrome patients. The
      relevance of this finding to the increased body fat present in patients with
      Cushing's syndrome merits further studies.

PMID- 9013749
TI  - Plasma leptin in depressed patients and healthy controls.
AB  - Leptin is known to regulate food intake and energy expenditure. Since loss of
      appetite and bodyweight are important signs and symptoms of major depression we
      studied leptin plasma concentrations in both depressed patients (n = 24)
      suffering from loss of appetite and a healthy control group (n = 33). To rule out
      the possibility of inferences with other endocrine parameters known to be changed
      in depression or suspected to be related to leptin, we also studied cortisol,
      insulin, growth hormone (GH) and GH-binding protein (GHBP). We found that leptin
      plasma concentrations did not differ between depressed patients and healthy
      controls. However, leptin was positively associated with female gender, body mass
      index (BMI) and morning insulin. 24-hour mean cortisol was not related to leptin.
      Also, GH and GHBP were not related to leptin when controlled for BMI in an ANCOVA
      model. We conclude that leptin plasma concentrations are unchanged in depression
      and that there is no evidence for leptin playing a major role in loss of appetite
      and body weight in depressed patients.

PMID- 9013750
TI  - Dissociation of serum leptin concentration and body fat content during long term
      dietary intervention in obese individuals.
AB  - High serum leptin concentrations are observed in humans with high body fat
      content, indicating leptin resistance. Reducing leptin levels by lowering body
      fat could restore leptin sensitivity. Our study was designed to clarify the
      relationship between changes in body composition and circulating leptin during a
      long term hypocaloric diet. 12 obese women and 10 obese men were included in a
      1000 kcal/day dietary intervention trial for 10 weeks. Body composition was
      measured by body impedance analysis and leptin by radioimmunoassay every 2 weeks.
      Body fat was reduced in females from 39.0 +/- 1.5 kg to 32.9 +/- 1.5 kg (p
      <0.001) and in males from 30.4 1.4 kg to 26.3 +/- 1.3 kg (p < 0.005). Plasma
      leptin decreased in females from 38.07 +/- 4.17 ng/ml to 18.90 +/- 2.75 ng/ml (p
      < 0.001) and in males from 10.58 +/- 2.16 ng/ml to 6.33 +/- 1.25 ng/ml (p <
      0.001). Non-linear regression analysis of leptin kinetics showed a comparable one
      phase exponential decline (y = Span x e(-K x x) + Plateau) in females (x +/- SEM:
      K = 0.48 +/- 0.01) and males (K = 0.60 +/- 0.01). Kinetics of body fat differed
      significantly from leptin data for females (K = 0.10 +/- 0.001, p < 0.001) but
      not for males (K = 0.27 +/- 0.02, p > 0.05). The leptin plateau was reached in
      both groups after 6- 8 weeks and the fat plateau in men after 10 weeks. Compared
      to healthy controls, some obese individuals had higher absolute values of leptin,
      but seemed to have a relative leptin deficiency when leptin was adjusted to body
      mass index according to a non-linear regression model of a large group of healthy
      women (n = 561) and men (n = 393). We conclude that during a long-term
      hypocaloric diet leptin uncouples from changes in body fat mass.

PMID- 9013752
TI  - Serum leptin levels following hypothalamic surgery.
AB  - To study a potential alteration of hypothalamic centers involved in the negative
      feedback action of leptin on body weight, serum leptin levels were measured in
      relation to BMI in 18 patients following surgery for a hypothalamic
      craniopharyngioma (Ctx), and were compared to levels found in 21 patients
      operated for a pituitary adenoma (Ptx) or in healthy control subjects. All
      subjects with Ptx received rhGH replacement therapy (0.5 to 2 IU/m2/d), and serum
      leptin levels were followed in 3 months intervals over 24 months. Serum leptin
      levels in patients with Ptx were comparable to controls, whereas 7 of the 18
      patients with Ctx had higher than expected concentrations for their BMI. GH
      treatment in Ptx subjects did not alter serum leptin levels. In 5 Ctx patients
      where preoperative samples were available, weight gain in parallel to an increase
      in serum leptin levels was observed but only minimal changes in 4 others. Our
      data support the role of leptin as an important marker of body weight. The rapid
      increase in serum leptin levels observed in some Ctx subjects suggests that early
      postoperative measurement of serum leptin levels may help to identify patients at
      risk of weight gain following hypothalamic destruction.

PMID- 9013751
TI  - Hyperleptinemia in chronic renal failure.
AB  - To investigate the mechanism(s) of degradation of leptin, the protein product of
      ob (obese) gene, we measured serum leptin levels in 70 patients with chronic
      renal failure (CRF). The median of serum leptin concentrations of 36 male and 34
      female patients with CRF were 7.3 ng/ml ranging from 0.5 to 39.0 ng/ml and 34.9
      ng/ml from 1.1 to 76.1 ng/ml, respectively, while those of 29 male and 29 female
      healthy subjects were 5.8 ng/ml ranging from 0.5 to 37.7 ng/ml and 12.0 ng/ml
      from 2.0 to 45.2 ng/ml, respectively. The difference in male and female serum
      leptin concentrations between CRF group and the normal counterpart was
      statistically significant (p<0.005 and p<0.05, respectively). However, there was
      no significant correlation, either between serum creatinine or BUN, and serum
      leptin concentrations. These findings suggest that leptin is degraded and/or
      filtered in renal tissue.

PMID- 9013753
TI  - Plasma leptin is directly related to body adiposity in subjects with spinal cord
      injury.
AB  - We addressed the relationship between plasma leptin and body mass index in 48
      able-bodied male controls and 34 male subjects with spinal cord injury, as well
      as the association between plasma leptin with body fat by dual energy x-ray
      absorptiometry in those with spinal cord injury. In subjects with spinal cord
      injury, the effect of an oral glucose tolerance test and the relationship of the
      serum lipid profile with plasma leptin levels were determined. Body mass index
      was not significantly different between the spinal cord injury and control
      groups. Plasma leptin was significantly higher in the group with spinal cord
      injury than in the control group (12.7 +/- 1.7 vs. 7.6 +/- 0.9 ng/ml, p < 0.005).
      A linear relationship was found between plasma leptin and body mass index in both
      groups separately (spinal cord injury: r = 0.59, p < 0.0002; control: r = 0.67, p
      < 0.0001). In those with SCI, a polynomial relationship was evident between
      plasma leptin and percent fat (r = 0.82, p < 0.0001). After an oral glucose load,
      plasma insulin levels and serum glucose concentrations were not related to plasma
      leptin levels. Serum triglycerides were found to be weakly correlated with plasma
      leptin levels (r = 0.35, p < 0.05). The higher plasma leptin levels in the group
      with spinal cord injury compared with the control group was probably due to a
      relatively increased percentage of adiposity in those with spinal cord injury.

PMID- 9013754
TI  - Circulating TNF-alpha and leptin levels in offspring of NIDDM patients do not
      correlate to individual insulin sensitivity.
AB  - Obesity plays a central role in the development of skeletal muscle insulin
      resistance. The molecular mechanism causing skeletal muscle insulin resistance in
      obese people is still poorly understood. It has been speculated that circulating
      factors derived from adipose tissue impair insulin signalling in the skeletal
      muscle cell. TNF-alpha and leptin, which are overproduced in fat tissue of obese
      insulin resistant animal models and in obese humans, might mediate such an
      inhibitory effect on insulin signalling in skeletal muscle. The aim of the
      present study was to evaluate whether circulating TNF-alpha and leptin correlates
      to the individual skeletal muscle insulin sensitivity in individuals with
      different degrees of obesity and insulin resistance. We measured circulating TNF
      alpha and leptin values in non diabetic offsprings of NIDDM patients. 36 German
      and 47 Finnish subjects participated in the study. The GDR of each participant
      was determined by the euglycemic hyperinsulinemic clamp technique, a range
      between 1.37 to 14.01 mg/kg LBM x min was observed. Percent of desirable body
      weight (PDW) covered also a wide range (87.58% to 197.06%). Although linear
      regression analysis suggested a dependence between TNF-alpha and GDR (Germany
      group: r = -0.37, p < 0.05, Finnish group: r = -0.32, p < 0.05) and a dependence
      between TNF and PDW (German group: r = 0.46, p < 0.05, Finnish group: r = 0.38, p
      < 0.05), in multiple linear regression analysis only the correlation with PDW was
      significant. Leptin levels were measured from 29 German and 36 Finnish subjects
      and a strong association was found between leptin and PDW (German group: r =
      0.55, p < 0.05, Finnish group: r = 0.73, p < 0.05). In contrast, leptin levels
      did not correlate with GDR and TNF-alpha. In summary, even though, in a few
      insulin resistant subjects, higher circulating TNF-alpha or leptin levels with
      the individual insulin sensitivity can be demonstrated, the data suggest that the
      circulating pool of TNF-alpha and leptin in blood is unlikely to be a major
      contributing factor for obesity induced insulin resistance in the vast majority
      of individuals at high risk to develop NIDDM.

PMID- 9013755
TI  - Obesity results as a consequence of glucocorticoid induced leptin resistance.

PMID- 9013756
TI  - Binding of leptin to the soluble ectodomain of recombinant leptin receptor: a
      kinetic analysis by surface plasmon resonance.

PMID- 9013757
TI  - Plasma leptin levels and body fat distribution.
AB  - The relation between body fat distribution and plasma leptin levels in the human
      was investigated in 51 obese and 41 non-obese subjects. Plasma levels of leptin
      showed a positive correlation with body mass index and subcutaneous fat area at
      the umbilicus level. However, a significant correlation between its plasma levels
      and visceral fat area was found in neither non-obese nor obese subjects. These
      results suggest that plasma leptin levels might be attributed mainly to the
      extent of subcutaneous adiposity in human obesity.

PMID- 9013758
TI  - Immunohistochemical detection of the ob gene product (leptin) in rat white and
      brown adipocytes.

PMID- 9013759
TI  - Characterization of the promoter of SF-1, an orphan nuclear receptor required for
      adrenal and gonadal development.
AB  - Steroidogenic factor 1 (SF-1) is a transcription factor shown to be critical for
      regulation of adrenal and gonadal development and function. To dissect the
      mechanisms that direct expression of this regulator, we have studied the promoter
      of the SF-1 gene and have identified cis-acting elements that recognize a basic
      helix-loop-helix transcription factor; the CAAT binding factor; and Sp1. We
      demonstrate in Y1 adrenocortical cells that a 90-bp proximal promoter fragment is
      sufficient to direct steroidogenic-specific expression and that all three
      elements are required for activity of the SF-1 promoter. Functional analysis of
      the binding sites on a heterologous TATA box-containing promoter demonstrates
      that the CAAT box and Sp1 site are not essential for promoter activity when a
      TATA box is present, whereas the E box is absolutely required for gene expression
      and is most likely the steroidogenic cell-specific element. We also demonstrate
      that SF-1 itself does not significantly affect the transcription of its own gene,
      and thus conclude that the E box, CAAT box, and Sp1 site of the proximal promoter
      direct expression of the SF-1 gene.

PMID- 9013760
TI  - Steroidogenic factor 1 (SF-1) and SP1 are required for regulation of bovine
      CYP11A gene expression in bovine luteal cells and adrenal Y1 cells.
AB  - Cholesterol side-chain cleavage cytochrome P450 (CYP11A; P450scc) gene expression
      is regulated by gonadotropins via cAMP in the ovary and by ACTH via cAMP in
      adrenal cortical cells. Previously, we have characterized a response element
      located at -118 to -101 bp in the 5'-flanking region of the bovine P450scc gene
      required for cAMP-stimulated transcription in both mouse adrenocortical Y1 cells
      and bovine ovarian cells in primary culture. It was shown that this region
      contains a binding site for the transcription factor Sp1. Deletion of this
      sequence abolished cAMP-stimulated transcription in both Y1 cells and bovine
      ovarian luteal cells. Another sequence element located at -57 to -32 bp upstream
      from the transcription initiation site, which is highly conserved in CYP11A of
      other species, contains the motif TAGCCTTG, similar to the consensus binding site
      of steroidogenic factor-1, SF-1 (or Ad4-BP), but in the inverted orientation. In
      the present study, gel shift analysis using nuclear extracts of either Y1 cells
      or bovine luteal cells demonstrated that the sequence between -57 and -32 bp
      bound SF-1. A mutation of the SF-1-binding site that abolished binding of the
      nuclear protein to DNA reduced markedly the basal transcription of the reporter
      gene as well as the responsiveness to cAMP, when the mutated fragments containing
      the region from -186 to +12 bp were cloned into a luciferase construct and
      transfected into mouse adrenal Y1 cells and bovine luteal cells. The role of SF-1
      in P450scc transcription was further confirmed by transactivation of the 
      186/+12Luc construct employing an SF-1 expression vector after transfection into
      nonsteroidogenic COS-1 cells. In addition, results obtained employing a double
      mutation of the Sp1- and SF-1-binding sites, and from a construct containing both
      Sp1 and SF-1 elements upstream of the CYP11A TATA box, indicated that Sp1 and SF
      1 function cooperatively in the transactivation of the bovine CYP11A promoter in
      both bovine luteal cells and Y1 cells. Finally, a mammalian two-hybrid system was
      employed to demonstrate that Sp1 and SF-1 can associate in vivo. These results
      establish that basal and cAMP-stimulated activity of the bovine P450scc promoter
      in both Y1 cells and bovine luteal cells requires the combined action of at least
      two transcription factors, Sp1 and SF-1.

PMID- 9013761
TI  - Characterization of the promoter region of the mouse gene encoding the
      steroidogenic acute regulatory protein.
AB  - Steroidogenic acute regulatory protein (StAR) delivers cholesterol to the inner
      mitochondrial membrane, where the cholesterol side-chain cleavage enzyme carries
      out the first committed step in steroid hormone biosynthesis. StAR expression is
      restricted to steroidogenic cells and is rapidly induced by treatment with
      trophic hormones or cAMP. We analyzed the 5'-flanking region of the mouse StAR
      gene to elucidate the mechanisms that regulate its cell-specific and hormone
      induced expression. In transient transfection assays, a luciferase reporter gene
      driven by the StAR 5'-flanking region was preferentially expressed by
      steroidogenic Y1 adrenocortical and MA-10 Leydig cells in a cAMP-responsive
      manner. 5'-Deletion and site-directed mutagenesis studies identified a region
      between -254 and -113 that is essential for full levels of promoter activity.
      This region contains a binding site for the orphan nuclear receptor steroidogenic
      factor-1 (SF-1) that, although not required for hormone induction, is critical
      for basal promoter activity, thus implicating SF-1 in StAR expression. Analyses
      of knockout mice deficient in SF-1 further supported an important role for SF-1
      in StAR gene expression. These studies provide novel insights into the mechanisms
      that regulate StAR gene expression and extend our understanding of SF-1's global
      roles within steroidogenic cells.

PMID- 9013762
TI  - An androgen response element in a far upstream enhancer region is essential for
      high, androgen-regulated activity of the prostate-specific antigen promoter.
AB  - Prostate-specific antigen (PSA) is expressed at a high level in the luminal
      epithelial cells of the prostate and is absent or expressed at very low levels in
      other tissues. PSA expression can be regulated by androgens. Previously, two
      functional androgen-response elements were identified in the proximal promoter of
      the PSA gene. To detect additional, more distal control elements, DNasel
      hypersensitive sites (DHSs) upstream of the PSA gene were mapped in chromatin
      from the prostate-derived cell line LNCaP grown in the presence and absence of
      the synthetic androgen R1881. In a region 4.8 to 3.8 kb upstream of the
      transcription start site of the PSA gene, a cluster of three DHSs was detected.
      The middle DNAseI-hypersensitive site (DHSII, at approximately -4.2 kb) showed
      strong androgen responsiveness in LNCaP cells and was absent in chromatin from
      HeLa cells. Further analysis of the region encompassing DHSII provided evidence
      for the presence of a complex, androgen-responsive and cell-specific enhancer. In
      transient transfected LNCaP cells, PSA promoter constructs containing this
      upstream enhancer region showed approximately 3000-fold higher activity in the
      presence than in the absence of R1881. The core region of the enhancer could be
      mapped within a 440-bp fragment. The enhancer showed synergistic cooperation with
      the proximal PSA promoter and was found to be composed of at least three separate
      regulatory regions. In the center, a functionally active, high-affinity androgen
      receptor binding site (GGAACATATTGTATC) could be identified. Mutation of this
      element almost completely abolished PSA promoter activity. Transfection
      experiments in prostate and nonprostate cell lines showed largely LNCaP cell
      specificity of the upstream enhancer region, although some activity was found in
      the T47D mammary tumor cell line.

PMID- 9013763
TI  - Mutant and wild-type androgen receptors exhibit cross-talk on androgen-,
      glucocorticoid-, and progesterone-mediated transcription.
AB  - Androgen, glucocorticoid, and progesterone receptors (ARs, GRs, and PRs) often
      can regulate transcription via composite hormone response elements in target
      genes. We have used artificial and natural mutant ARs from patients with androgen
      resistance to study their effects on dominant negative activity on wild type AR,
      GR, and PR function on mouse mammary tumor virus (MMTV) and tyrosine
      aminotransferase (TAT) promoters. Artificial ARs that contained internal
      deletions within the amino-terminal region had minimal transcriptional activity
      but blocked ligand-mediated transcription by wild type AR. Mutants containing
      deletions of the DNA-binding and ligand-binding domains had minimal or weak
      dominant negative activity. We then tested the ability of wild type and mutant
      ARs to modulate GR- and PR-mediated transcriptional activity. The amino-terminal
      deletion mutants exerted dominant negative effects on GR- and PR-mediated
      activity, both in the absence and presence of testosterone. Surprisingly, wild
      type AR, which had approximately 20% of the maximal transcriptional activity of
      GR on the MMTV promoter, also had dominant negative activity on dexamethasone
      regulated transcription mediated by GR. This dominant negative activity likely
      involves DNA binding because a point mutation in the DNA-binding domain abrogated
      such activity of an amino-terminal deletion mutant. Additionally, natural human
      AR mutants from patients with androgen resistance, which do not bind either DNA
      or ligand, did not block dexamethasone-mediated transcription. In summary, these
      studies suggest that mutant and wild type ARs can display dominant negative
      activity on other steroid hormone receptors that bind to a composite hormone
      response element This cross-regulation may be important in regulating maximal
      transcriptional activity in tissues where these receptors are coexpressed and may
      contribute to the phenotype of patients with steroid hormone resistance.

PMID- 9013764
TI  - Estrogen receptor-beta mRNA expression in rat ovary: down-regulation by
      gonadotropins.
AB  - We have examined the expression and regulation of the two estrogen receptor (ER
      alpha and ER beta) genes in the rat ovary, using Northern blotting, RT-PCR, and
      in situ hybridization histochemistry. Northern blotting results show that the
      ovary expresses both ER alpha and ER beta genes as single (approximately 6.5-kb)
      and multiple (ranging from approximately 1.0-kb to approximately 10.0-kb)
      transcripts, respectively. ER alpha mRNA is expressed at a level lower than ER
      beta mRNA in immature rat ovaries. This relationship appears unchanged between
      sexually mature adult rats and immature rats. In sexually mature adult rats
      undergoing endogenous hormonal changes, whole ovarian content of ER beta mRNA, as
      determined by RT-PCR, remained more or less constant with the exception of the
      evening of proestrus when ER beta mRNA levels were decreased. Examination of ER
      beta mRNA expression at the cellular level, by in situ hybridization, showed that
      ER beta mRNA is expressed preferentially in granulosa cells of small, growing,
      and preovulatory follicles, although weak expression of ER beta mRNA was observed
      in a subset of corpora lutea, and that the decrease in ER beta mRNA during
      proestrous evening is attributable, at least in part, to down-regulation of ER
      beta mRNA in the preovulatory follicles. This type of expression and regulation
      was not typical for ER alpha mRNA in the ovary. Although whole ovarian content of
      ER alpha mRNA was clearly detected by RT-PCR, no apparent modulation of ER alpha
      mRNA levels was observed during the estrous cycle. Examination of ER alpha mRNA
      expression at the cellular level, by in situ hybridization, showed that ER alpha
      mRNA is expressed at a low level throughout the ovary with no particular cellular
      localization. To further examine the potential role of the preovulatory pituitary
      gonadotropins in regulating ER beta mRNA expression in the ovary, we used
      immature rats treated with gonadotropins. In rats undergoing exogenous hormonal
      challenges, whole ovarian content of ER beta mRNA, as determined by RT-PCR,
      remained more or less unchanged after an injection of PMSG. In contrast, a
      subsequent injection of human CG (hCG) resulted in a substantial decrease in
      whole ovarian content of ER beta mRNA. In situ hybridization for ER beta mRNA
      shows that small, growing, and preovulatory follicles express ER beta mRNA in the
      granulosa cells. The preovulatory follicles contain ER beta mRNA at a level lower
      than that observed for small and growing follicles. In addition, there is an
      abrupt decrease in ER beta mRNA expression in the preovulatory follicles after
      hCG injection. The inhibitory effect of hCG on ER beta mRNA expression was also
      observed in cultured granulosa cells. Moreover, agents stimulating LH/CG receptor
      associated intracellular signaling pathways (forskolin and a phorbol ester)
      readily mimicked the effect of hCG in down-regulating ER beta mRNA in cultured
      granulosa cells. Taken together, our results demonstrate that 1) the ovary
      expresses both ER alpha and ER beta genes, although ER beta is the predominant
      form of estrogen receptor in the ovary, 2) ER beta mRNA is localized
      predominantly to the granulosa cells of small, growing, and preovulatory
      follicles, and 3) the preovulatory LH surge down-regulates ER beta mRNA. These
      results clearly implicate the physiological importance of ER beta in female
      reproductive functions.

PMID- 9013766
TI  - RIP 140 enhances nuclear receptor-dependent transcription in vivo in yeast.
AB  - RIP140 has previously been cloned as a factor that interacts with the estrogen
      receptor (ER) in vitro. We demonstrate in this study that RIP140 is a co-factor
      for nuclear receptor in yeast. RIP140 enhances the ER transcriptional activity by
      increasing 1.5- to 4-fold the induction factor of the reporter gene response at
      saturating hormone concentrations, this effect being magnified at suboptimal
      doses of estradiol. Moreover, RIP140 decreases the ED50 of the dose-response
      curve. These effects are recovered with an N-terminal truncated ER, but impaired
      by point mutations that abolish AF2-AD activity. We did not observe any
      modulation of the partial agonist 4-hydroxytamoxifen activity in the presence of
      RIP140. Thus, RIP140 modulates transcriptional activity of ER through the AF2-AD
      domain and in a agonist-dependent fashion. RIP140 is also a strong coactivator
      for the retinoid pathway, as its expression enhances 10-fold the transactivation
      of a chimeric retinoic acid-alpha receptor at saturant hormone concentration and
      left shifted 5-fold the ED50 of the dose-response curve. We have investigated
      whether RIP140 could be involved in cross-talk between estrogenic and retinoid
      pathways.

PMID- 9013765
TI  - Phosphorylation of the lutropin/choriogonadotropin receptor facilitates
      uncoupling of the receptor from adenylyl cyclase and endocytosis of the bound
      hormone.
AB  - Stably transfected cell lines expressing the wild-type rat LH/CG receptor (rLHR)
      or a full-length rLHR in which S635, T638, S639, S649 and S653 were
      simultaneously mutated to alanine residues (designated rLHR-5S/T-->A) were used
      to probe the importance of receptor phosphorylation on the regulation of receptor
      functions. The mutant receptor binds hCG with high affinity and transduces the
      hormonal signal into increases in cAMP and inositol phosphate accumulation
      comparable in magnitude to those elicited by the wild-type receptor. In contrast
      to cells expressing rLHR-wt, which respond to hCG or phorbol 12-myristate 13
      acetate stimulation with an increase in rLHR phosphorylation, the phosphorylation
      of rLHR in cells expressing rLHR-5S/T-->A is severely blunted. Likewise, the
      phorbol 12-myristate 13-acetate-induced desensitization of hCG-induced cAMP
      accumulation is drastically reduced in cells expressing rLHR-5S/T-->A. In
      contrast, the hCG-induced desensitization of hCG-induced cAMP accumulation is
      delayed, but not abolished, in cells expressing rLHR-5S/T-->A. Lastly, the rate
      of internalization of the receptor-bound hCG is slower in cells expressing rLHR
      5S/T-->A than in cells expressing rLHR-wt. These results show that
      phosphorylation of rLHR is necessary, but not sufficient, for uncoupling of the
      receptor from adenylyl cyclase and for endocytosis of the receptor-bound hormone.

PMID- 9013767
TI  - The caudal homeobox protein cdx-2/3 activates endogenous proglucagon gene
      expression in InR1-G9 islet cells.
AB  - The proglucagon gene is expressed in a highly cell-specific manner in islet and
      enteroendocrine cells. DNA sequences within the proximal proglucagon G1 promoter
      region bind the homeobox protein cdx-2/3, and cdx-2/3 activates the proglucagon
      promoter in fibroblasts. We show here that cdx-2/3 activates the proglucagon
      promoter in both islet (InR1-G9) and enteroendocrine (STC-1 and GLUTag) cell
      lines. Furthermore, transfected cdx-2/3 increased the levels of endogenous
      proglucagon mRNA transcripts in both transient and stable transfections of InR1
      G9 islet cells. The cdx-2/3-dependent induction of endogenous proglucagon mRNA
      transcripts in stable islet lines was associated with a corresponding increase in
      the transcriptional activity of proglucagon promoter-luciferase plasmids. An
      amino-terminally truncated cdx-2/3 derivative containing the homeodomain and
      carboxy-terminal region of the molecule inhibited both the cdx-2/3 activation of
      the proglucagon promoter and the induction of endogenous proglucagon mRNA
      transcripts. These observations demonstrate that cdx-2/3, acting through the
      proximal G1 element, is a major transcriptional determinant of cell-specific
      proglucagon gene expression in pancreatic islet cells.

PMID- 9013768
TI  - DNA sequences downstream from the vitamin D response element of the rat
      osteocalcin gene are required for ligand-dependent transactivation.
AB  - The sequences in the rat osteocalcin gene that lie 3' to the vitamin D response
      element (VDRE) have been shown to augment transcriptional activation by 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3]. These DNA sequences, however, are unable to
      bind the VDR or mediate 1,25-(OH)2D3 responsiveness independently of the VDRE. To
      further characterize this region, the functional properties of a series of mutant
      oligonucleotides were examined in transiently transfected ROS 17/2.8 cells. When
      these mutant oligonucleotides were expressed upstream of the heterologous herpes
      simplex virus thymidine kinase promoter, the bases between -420 and -414 of the
      rat osteocalcin gene were identified as critical for maximal transactivation by
      1,25-(OH)2D3. Furthermore, mutation of these sequences in the context of the
      native osteocalcin promoter and enhancer totally abolished the ability of the
      VDRE to mediate 1,25-(OH)2D3 responsiveness. These bases, which are essential for
      the 1,25-(OH)2D3 responsiveness of the rat osteocalcin gene, are also present in
      a similar position, relative to the VDRE, in the human osteocalcin gene. To
      explore whether these sequences could enhance transactivation by other inducible
      transcription factors, they were examined for their ability to synergize with the
      chick vitellogenin estrogen response element and the rat somatostatin cAMP
      response element. When placed upstream to the herpes simplex virus thymidine
      kinase promoter and transfected into ROS 17/2.8 cells, these sequences were able
      to enhance transcriptional responsiveness to 17beta-estradiol and forskolin,
      respectively, demonstrating that they also contribute to transactivation by other
      inducible transcription factors.

PMID- 9013770
TI  - A prolactin-inducible T cell gene product is structurally similar to the
      Aspergillus nidulans nuclear movement protein NUDC.
AB  - Clone 15 (c15) was originally identified as a PRL-inducible gene in activated T
      cells. Sequence analysis of c15 revealed that the last 94 amino acids of c15 are
      68% identical and 78% similar to the filamentous fungus Aspergillus nidulans
      nuclear movement protein NUDC. The identification of the mammalian (rat) c15
      protein suggests that the carboxy-terminal NUDC-like region has been conserved
      over evolution for an important structure and/or function. To determine whether
      c15 is functionally analogous to NUDC, complementation studies were performed
      using the inducible/repressible pAL5 vector system. The results of the
      complementation experiments show that the full-length mammalian c15 protein is
      not only capable of rescuing the nuclear movement defect of the nudC3 mutants,
      but is also able to restore the expression of the downstream endogenous NUDF
      protein to near wild type levels. These results indicate that rat c15 and fungal
      NUDC not only share similar structures, but also serve similar functions. Taken
      together, the structural and functional conservation between c15 and NUDC is
      consistent with the notion that c15 is the rat homolog of nudC and has therefore
      been given the name RnudC.

PMID- 9013769
TI  - The N-terminal domain of transcription factor IIB is required for direct
      interaction with the vitamin D receptor and participates in vitamin D-mediated
      transcription.
AB  - The interaction of the vitamin D receptor (VDR) with transcription factor IIB
      (TFIIB) represents a potential physical link between the VDR-DNA complex and the
      transcription preinitiation complex. However, the functional relevance of the VDR
      TFIIB interaction in vitamin D-mediated transcription is not well understood. In
      the present study, we used site-directed mutagenesis to demonstrate that the
      structural integrity of the amino-terminal zinc finger of TFIIB is essential for
      VDR-TFIIB complex formation. Altering the putative zinc-coordinating residues
      (C15, C34, C37, or H18) to serines abolished TFIIB interaction with the VDR as
      assessed in a yeast two-hybrid system and by in vitro protein interaction assays.
      This N-terminal, VDR-interactive domain functioned as a selective, dominant
      negative inhibitor of vitamin D-mediated transcription. Expressing amino acids 1
      124 of human TFIIB (N-TFIIB) in COS-7 cells or in osteoblastic ROS17/2.8 cells
      effectively suppressed 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-induced
      transcription, but had no effect on basal or glucocorticoid-activated
      transcription. A mutant N-terminal domain [N-TFIIB(C34S:C37S)] that does not
      interact with VDR had no impact on 1,25-(OH)2D3-induced transcription.
      Interestingly, both in vitro and in vivo protein interaction assays showed that
      the VDR-TFIIB protein complex was disrupted by the 1,25-(OH)2D3 ligand.
      Mechanistically, these data establish a functional role for the N terminus of
      TFIIB in VDR-mediated transcription, and they allude to a role for unliganded VDR
      in targeting TFIIB to the promoter regions of vitamin D-responsive target genes.

PMID- 9013771
TI  - A functional Sp1 binding site is essential for the activity of the adult liver
      specific human insulin-like growth factor II promoter.
AB  - The human gene encoding insulin-like growth factor II contains four promoters (P1
      P4) that are differentially activated in various tissues during development.
      Expression of insulin-like growth factor II in adult liver tissue is directed by
      P1, which is activated by liver-enriched members of the CCAAT/enhancer binding
      protein family of transcription factors. In the present report we show that the
      region around -48 relative to the transcription start site contains a high
      affinity Sp1 binding site. This was demonstrated by electrophoretic mobility
      shift assays using nuclear extracts from Hep3B hepatoma cells and with specific
      antibodies directed against Sp1. Competition electrophoretic mobility shift
      assays revealed that the Sp1 binding site of P1 and a consensus Sp1 binding site
      bind Sp1 with comparable efficiencies. Mutation of the Sp1 binding site results
      in an 85% decrease in P1 promoter activity in transient transfection assays using
      two different cell lines, COS-7 and Hep3B. Investigation of P1 mutants in which
      the spacing of the Sp1 binding site and the transcription start site was
      increased showed that the role of the Sp1 binding site in regulation of P1 is
      position dependent. Interestingly, the Sp1-responsive element cannot be exchanged
      by a functional TATA box. Activation of P1 by transactivators CCAAT/enhancer
      binding protein-beta and hepatocyte nuclear factor-3beta is strongly impaired
      after mutation of the Sp1 binding site. These results demonstrate that the
      specific presence of a binding site for the ubiquitously expressed transcription
      factor Sp1 is of eminent importance for efficient activation of P1 by liver
      enriched transactivators.

PMID- 9013773
TI  - Region-specific central nervous system expression and axotomy-induced regulation
      in sympathetic neurons of a VIP-beta-galactosidase fusion gene in transgenic
      mice.
AB  - To assess the activity of cis-acting elements that direct human vasoactive
      intestinal peptide (VIP) expression in vivo, two independent transgenic mouse
      lines were created using a transgene comprised of 1.9 kb of 5'-flanking sequence
      of the human VIP gene joined to the Escherichia coli beta-galactosidase reporter
      gene. Transgene expression in brain was assessed using beta-galactosidase
      histochemistry and compared to the distribution of endogenous VIP expression.
      Transgene expression was observed in most central and peripheral nervous system
      sites in which endogenous VIP is expressed. We investigated whether the VIP-beta
      galactosidase transgene was regulated in sympathetic neurons in experimental
      paradigms in which VIP regulation is dependent on the release of leukemia
      inhibitory factor (LIF). After dissociation in vitro and postganglionic axotomy
      in vivo there were parallel increases in endogenous VIP and transgene expression
      in superior cervical ganglia. These results indicate that the 1.9 kb region of 5'
      flanking sequence of the human VIP gene includes genomic elements important for
      cell-specific expression and LIF-dependent regulation in neurons.

PMID- 9013772
TI  - The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for
      insulin and cytokine action.
AB  - Signal transduction by insulin and IGF-1, several interleukins (IL-2, IL-4, IL-9,
      IL-13), interferons, GH, and other cytokines involves IRS proteins, which link
      the receptors for these factors to signaling molecules with Src homology-2
      domains (SH2-proteins). We recently reported the amino acid sequence of murine
      IRS-2; in order to examine a potential genetic role for this molecule in disease,
      we isolated the murine IRS-2 gene and compared the expression pattern of IRS-2
      against IRS-1. Like IRS-1, IRS-2 is encoded by a single exon. Whereas IRS-1 is
      located on murine chromosome 1, IRS-2 is located on murine chromosome 8 near the
      insulin receptor. IRS-2 is expressed together with IRS-1 in many cells and
      tissues; however, IRS-2 predominates in murine hematopoietic cells where it may
      be essential for cytokine signaling; IRS-1 predominates in adipocytes and
      differentiated 3T3-L1 cells where it contributes to the normal insulin response.
      In 32D cells, IRS-1 and IRS-2 undergo differential tyrosine phosphorylation
      during insulin or IL-4 stimulation, as assessed indirectly by interaction with
      various recombinant SH2 domains. Thus, signaling specificity through the IRS
      proteins may be accomplished by specific expression patterns and distinct
      phosphorylation patterns during interaction with various activated receptors.

PMID- 9013774
TI  - Light-induced c-fos mRNA expression in the suprachiasmatic nucleus and the retina
      of C3H/HeN mice.
AB  - Light-induced expression of c-fos mRNA was studied over a circadian period
      (approximately 24 h) in C3H/HeN mice maintained in constant dark. This mouse
      strain expresses an rd mutation (retinal degeneration) which does not affect
      light-induced phase shifts of circadian rhythms. c-fos mRNA expression in the
      retina and the suprachiasmatic nucleus (SCN) after a light pulse (300 lux) was
      determined by in-situ hybridization autoradiography using a 35S-labeled c-fos
      riboprobe. Light induced the expression of c-fos mRNA in retino-recipient areas
      of the SCN. This response was dependent on the circadian time (CT) and was
      observed only during the subjective night (CT14-CT22) and early subjective day
      (CT2). However, the period of photosensitivity for c-fos induction extended 1 h
      over the period of photosensitivity for phase shifts in circadian behavior. In
      the retina of C3H/HeN mice, light-induced c-fos mRNA expression was observed in a
      small number of cells in the ganglion cell layer (approximately 0.2%) which may
      represent ganglion cells projecting to the SCN. A dependence of c-fos expression
      with the circadian time was observed in retinal ganglion cells, suggesting that
      retinal photosensitivity may also be controlled by a circadian oscillator. In
      conclusion, we demonstrated light-induced expression of the immediate early gene
      c-fos mRNA in both the retina and SCN of C3H/HeN mice expressing the rd mutation.

PMID- 9013776
TI  - In vivo regulation of neurotensin receptors following long-term pharmacological
      blockade with a specific receptor antagonist.
AB  - Adaptive changes in brain neurotensin (NT) receptors were investigated in rats
      after repeated administration of SR 48692, a potent and selective non-peptide NT
      receptor antagonist. Administration of SR 48692 (1 mg/kg i.p.) for 15 days did
      not alter NT content in the brain but highly enhanced the expression of NT
      receptor mRNA as shown by quantitative in situ hybridization. The increase of the
      signal was observed in numerous areas of the brain, such as the anterior
      cingulate, perirhinal and retrosplenial cortices, the suprachiasmatic nucleus,
      the ventral tegmental area, the substantia nigra and the posterior cortical
      nucleus of the amygdaloid complex. Moreover, the SR 48692 treatment induced the
      expression of NT receptor mRNA in several nuclei of the diencephalon where it
      could not be detected in basal conditions. Immunoblot analysis with a specific
      antibody directed against the rat cloned NT receptor revealed an important
      increase in NT receptor protein in the brain of SR 48692-treated rats,
      correlating well with the increase in NT receptor mRNA levels. Surprisingly, the
      number and the affinity constant of NT binding sites determined on brain membrane
      homogenates remained unchanged after SR 48692 treatment, even after membrane
      permeabilization with low concentrations of digitonin. These results suggest that
      chronic treatment with a specific NT antagonist induces an up-regulation of NT
      receptors at the level of mRNA and protein. Moreover, they indicate that after a
      chronic treatment with SR 48692, the number of NT binding sites remains stable in
      contrast to what is observed after 5-day treatment or with central monoaminergic
      receptor following their long-term blockade.

PMID- 9013775
TI  - Variable subcellular localization of a neuron-specific protein during NTera 2
      differentiation into post-mitotic human neurons.
AB  - The current report describes the molecular characterization of the human (the
      D4S234 locus) and mouse (the m234) homologs of a gene that was isolated during
      our genomic analysis of the Huntington disease gene region. Sequence comparisons
      of full-length cDNA clones revealed that the mouse and human homologs encoded
      evolutionarily conserved 21-kDa proteins with greater than 90% amino acid
      sequence identity. Extensive sequence identity between the D4S234 gene and the
      rat p1A75 gene (a previously identified rat neuron-specific gene) showed that
      these genes are interspecies homologs. Furthermore, the D4S234 protein exhibited
      significant amino acid similarity to a 19-kDa mouse protein that localizes to the
      Golgi apparatus of embryonic neurons. However, nonconservative sequence
      differences suggested that these genes are independent members of a multigene
      family. Northern analyses revealed that rodent D4S234 expression occurred
      predominantly in the brain and included all brain regions. Neuron-specific
      expression was demonstrated using Northern analysis of cultured glial cells and
      quinolinic acid-treated rat brain samples. Minimal amounts of the rodent D4S234
      mRNA were detected prenatally; however, elevated adult levels were detected
      within 1 month of birth. Sequence analyses of the human and mouse D4S234 proteins
      identified an evolutionarily conserved hydrophobic sequence and a consensus
      nuclear localization signal in both genes. Immunofluorescence microscopy, using
      an antipeptide antibody, established that the human D4S234 protein preferentially
      localized to the nucleus of mitotic cultured cells. Since the rat p1A75 protein
      was previously mapped to the neuronal cytoplasm by in situ hybridization, the
      subcellular localization of the D4S234 protein was subsequently examined during
      differentiation of the NTera 2 (NT2) cell line. Following differentiation into
      postmitotic NT2-N neurons, the D4S234 protein demonstrated cytoplasmic staining
      and reduced or undetectable nuclear staining in many cells. The variation in the
      intracellular localization of the D4S234 protein in mitotic and nonmitotic cells
      suggests that the subcellular localization of this protein is developmentally
      regulated and provides clues about the biochemical function of this protein.

PMID- 9013777
TI  - Sequence of the voltage-gated sodium channel beta1-subunit in wild-type and in
      quivering mice.
AB  - SCN1B, the human gene encoding the beta1-subunit of the voltage-gated sodium
      channel has previously been cloned and mapped to Chr 19q13.1. The sequence of the
      homologous mouse gene, Scn1b, has now been determined from cDNA. The mouse gene
      is highly conserved, encoding a predicted protein with 99%, 98% and 96% amino
      acid identity to the rat, rabbit, and human homologs, respectively. DNA sequence
      conservation is also striking in the 3' untranslated region which shows 67% and
      98% to human and rat, respectively. Unlike the human and rat homologs, high
      expression of mRNA from the mouse gene is confined to adult skeletal muscle and
      brain, and is not observed in heart. As Scnlb maps to Chr 7, in close genetic
      proximity to the quivering gene (qv), the coding region of Scnlb was also cloned
      from a qvJ/qvJ homozygous mouse and assessed as a candidate for the site of this
      genetic defect. Comparison of qv and wild-type cDNAs showed no changes in the
      predicted amino acid sequence that could cause the qv phenotype. However, three
      silent polymorphisms in the DNA coding region indicate that Scn1b is close to qv,
      and is within a region of genetic identity with DBA/2J, the inbred background on
      which the qvJ allele arose.

PMID- 9013778
TI  - Effect of thyroid hormone deficiency on RC3/neurogranin mRNA expression in the
      prenatal and adult caprine brain.
AB  - Thyroid hormone deficiency has profound effects on the brain during development
      and less marked effects on the adult brain. These effects are considered to be
      the result of the direct regulation of specific target genes by thyroid hormone.
      Previous studies have shown that the expression of the neuronal gene RC3,
      encoding a 78-amino-acid calmodulin-binding protein kinase C substrate, is under
      the influence of thyroid hormone in vivo. In congenitally hypothyroid foetal goat
      at term (approximately 150 days of gestation), RC3 mRNA expression was reversibly
      decreased in the striatum but not in other brain regions. In the present study we
      investigated the role of thyroid hormone in RC3 mRNA expression at earlier stages
      of fetal development and in mature goats using in situ hybridization. There was a
      consistent decrease (35-80%) in the signal for RC3 mRNA per neuron in the
      striatum of hypothyroid adult and fetal goats of 90, 120 and 150 days of
      gestation compared to normal goats of the same age. In contrast, no consistent
      difference was observed in the cerebral cortex at any age studied. These data
      indicate that in both fetal and adult goats thyroid hormone, at least partly,
      affects the expression of RC3 mRNA in the striatum and not the cerebral cortex.

PMID- 9013779
TI  - Focal cerebral ischaemia increases the levels of several classes of heat shock
      proteins and their corresponding mRNAs.
AB  - The induction of focal cerebral ischaemia in rats by middle cerebral artery
      occlusion has previously been shown to increase, over time, the mRNA levels of
      the heat shock proteins (HSPs) 27 and 70. However, the levels of HSP90 mRNA
      remain constant. In contrast, during global ischaemia, HSP70 and HSP90 mRNA
      levels are both raised, particularly in the CA1 neurons in the hippocampus, an
      area that is resistant to the insult in comparison to the surrounding regions.
      HSP27 mRNA is raised in the neuroglia in the subregions of the hippocampus.
      However, the protein levels of HSP27, 70 and 90 have not been characterised in
      focal ischaemia. With this data in mind, we have carried out a comparative study
      of HSP27, 56, 60, 70 and 90 mRNA and protein levels during focal cerebral
      ischaemia in rats, up to 24 h post-occlusion. We have shown that HSP70 and HSP27
      mRNA levels are increased and also that HSP60 mRNA levels (which had also not
      previously been characterised in this model of focal ischaemia) are significantly
      raised. HSP90 and HSP56 mRNAs were not significantly elevated. On Western blot
      analysis, the inducible HSP72 protein was first detected at 8 h post-occlusion,
      HSP27 protein was detected only at 24 h post-occlusion and HSP60 protein,
      although constitutive, appeared to increase at 24 h post-occlusion. HSP56 protein
      levels appeared to rise on the occluded side, but HSP90 protein levels remained
      constant.

PMID- 9013780
TI  - Cloning, characterization, and chromosomal localization of rec1.3, a member of
      the G-protein-coupled receptor family highly expressed in brain.
AB  - During a project to identify G-protein-coupled receptors (GPCR) expressed within
      taste buds, we have isolated a novel receptor-like sequence. The full length
      sequence of this receptor (rec1.3) has been obtained in both cow and mouse.
      Rec1.3 bears little sequence similarity to any GPCR whose ligand is known: the
      closest identity (33%) is to the orphan receptor edg-1. In cow, rec1.3 is
      expressed most prominently in the brain, with moderate expression in testis and
      tongue; in the mouse the expression is more widespread. No specific binding for a
      range of ligands was detected when the mouse coding sequence was expressed in
      eukaryotic cells. In situ hybridization showed that rec1.3 is widely expressed
      throughout the mouse brain and is highly expressed in localized regions of the
      hindbrain, midbrain and hypothalamus. The rec1.3 gene was localized to the
      centromeric region of chromosome 4 in mouse, a region associated with neonatal
      seizures.

PMID- 9013781
TI  - Characterization of gonadotropin-releasing hormone gene transcripts in a mouse
      hypothalamic neuronal GT1 cell line.
AB  - We have characterized the nuclear and cytoplasmic RNA transcripts derived from
      the gonadotropin releasing hormone (GnRH) gene in a mouse hypothalamic neuronal
      GT1 cell line. Analyses of nuclear GnRH RNA precursors present in the GT1 cells
      by RNase protection assay show that there is no particular order of intron
      excision, suggesting the existence of multiple processing pathways. A similar
      pattern is observed in mouse preoptic area-anterior hypothalamus (POA-AH). In GT1
      cells, approximately 5% of the total GnRH RNA transcripts are found in the
      nucleus. In contrast, in the POA-AH of mice, nuclear transcripts comprise 40% of
      the total GnRH transcripts. Thus the GT1 cells, while similar in overall GnRH RNA
      processing to mouse hypothalamic GnRH neurons, do not exhibit the high abundance
      of nuclear GnRH RNA transcripts seen in the rodent GnRH neuron in vivo.
      Quantitative analysis of the nuclear RNA species shows that the GnRH primary
      transcript comprises more than 90% of the total nuclear GnRH mRNA precursors in
      both GT1 cells and mouse POA-AH and thus GnRH processing intermediates account
      for fewer than 10% of these precursors. Using these probes, we have examined
      changes in GnRH primary transcript expression in GT1-7 cells. In the presence of
      RNA synthesis inhibitors, the half-life of the GnRH primary transcript was found
      to be quite short, approximately 18 min, suggesting that the level of primary
      transcript would reflect levels of GnRH gene transcription. When GT1-7 cells are
      treated with the phorbol ester PMA (phorbol, 12-myristate, 13-acetate) for 1 h,
      GnRH primary transcript levels decrease by approximately 70%. Supporting the
      hypothesis that GnRH primary transcript is a good indicator of GnRH gene
      transcription is the finding that 1 h of PMA treatment results in a similar
      (approximately 50%) decrease in GnRH gene transcription, as assayed by nuclear
      run-on assay. Our observation that GT1 cells resemble mouse hypothalamic GnRH
      neurons in their pattern of intron excision and in the ratio of primary
      transcript to other nuclear transcripts emphasizes the utility of these cells for
      studying the regulation of GnRH gene expression in this immortalized hypothalamic
      cell line.

PMID- 9013782
TI  - Distinct localization of two serine-threonine kinase receptors for activin and
      TGF-beta in the rat brain and down-regulation of type I activin receptor during
      peripheral nerve regeneration.
AB  - The localizations of serine-threonine kinase receptor mRNA for the novel type I
      TGF-beta and/or activin receptor named B1 (rat), ALK-4 (mouse) or ActR-IB (human)
      were demonstrated by in situ hybridization. As the putative ligand for this
      receptor in the brain has not yet been clearly determined, we compared its
      localization to type II activin receptor (ActR-II) which is the counterpart of
      the type I activin receptor. B1 mRNA was widely observed in neuronal cells
      throughout the brain, and especially strong positive signals were found in the
      cerebral cortex, olfactory tubercle, and hippocampus. The localization of B1 mRNA
      coincided well with that of ActR-II. This strongly suggests that B1 (ALK-4/ActR
      IB) could be the type I activin receptor, as type I and type II activin receptor
      were supposed to form a receptor complex. In addition, we examined the
      localization of type II TGF-beta receptor (TbetaRII) mRNA which is an essential
      counterpart of the type I TGF-beta receptors for TGF-beta signaling. TbetaRII
      mRNA was expressed mainly in non-neuronal cells such as choroid plexus. In
      addition, TbetaRII mRNA expression was also found in a minor population of
      neuronal cells. TbetaRII mRNA-positive neurons were observed in the reticular
      thalamus, laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus and
      the ventral tegmental nucleus. The localization of TbetaRII was markedly
      different from that of activin receptors in the rat brain. Since TGF-betas and
      activins are known as growth factors and/or survival factors, we examined changes
      in levels of B1 and TbetaRII mRNA expression during peripheral nerve
      regeneration. Expression of B1 mRNA in the axotomized hypoglossal motoneurons was
      substantially decreased from day 3 after axotomy and this decrease was
      significant until postoperative day 28, whereas no TbetaRII signal was observed
      in hypoglossal nucleus prior or after axotomy. This transient down-regulation of
      B1 mRNA expression suggests that activin signaling is somehow suppressed during
      peripheral nerve regeneration.

PMID- 9013783
TI  - Effect of streptozotocin-diabetes on knee joint inflammation-induced changes in
      substance P and nerve growth factor in the rat.
AB  - Given the involvement of the sensory nervous system in the aetiology of
      neurogenic inflammation, we have investigated the effect of experimental diabetes
      and any associated sensory nerve dysfunction on the development of complete
      Freund's adjuvant-induced inflammation in the rat knee. Twenty-four hours after
      induction of inflammation in non-diabetic rats, gamma-preprotachykinin mRNA
      expression was increased in the L4/L5 dorsal root ganglia. Substance P levels
      were increased in dorsal root ganglia and sciatic nerve whilst synovial levels of
      substance P were significantly decreased. Nerve growth factor, which regulates
      expression of gamma-preprotachykinin mRNA, was significantly increased in
      synovium and sciatic nerve after induction of inflammation. After 24 weeks of
      streptozotocin-diabetes, there was a non-significant reduction in gamma
      preprotachykinin mRNA expression whilst substance P levels in dorsal root
      ganglia, sciatic nerve and synovium and nerve growth factor levels in the sciatic
      nerve were significantly decreased. Conversely, synovial levels of nerve growth
      factor were significantly increased. Injection of complete Freund's adjuvant into
      the knee of diabetic rats produced diminished joint swelling compared to that
      observed in non-diabetic rats. Substance P levels were unaltered compared to non
      arthritic diabetic rats whilst nerve growth factor levels were significantly
      increased in synovium and sciatic nerve suggesting an uncoupling of substance P
      from nerve growth factor control in the inflammatory response in diabetic rats.
      The results show a significant reduction in the inflammatory response in rats
      with chronic streptozotocin-diabetes. Deficits in gamma-preprotachykinin mRNA
      expression and substance P and the altered levels of nerve growth factor indicate
      sensory neuronal dysfunction may play a major role in this abnormal response.

PMID- 9013784
TI  - Calbindin-D28k mRNA expression in magnocellular hypothalamic neurons of female
      rats during parturition, lactation and following dehydration.
AB  - Recent studies indicate that calcium binding proteins may play a role in
      determining the electrical firing patterns of the hypothalamic magnocellular
      oxytocin (OT) and vasopressin (VP) neurons. In this study we have examined the
      calbindin-D28k mRNA content of magnocellular neurons in the supraoptic (SON) and
      paraventricular (PVN) nuclei and determined whether changes in expression
      correlate with the specific patterns of electrical activity displayed by these
      cells under different physiological circumstances. In situ hybridization with
      [35S]-labelled oligonucleotides revealed a heterogeneous pattern of calbindin
      D28k mRNA expression in the SON and magnocellular PVN. Quantitative analysis
      demonstrated that the number of silver grains/cell in the dorsal half of the SON
      was approximately 30% higher (P < 0.05) than that of the ventral half of the
      nucleus. Within the PVN, calbindin-D28k mRNA-expressing neurons were detected in
      the medial magnocellular division of the PVN but not in magnocellular cells
      forming the core of the lateral magnocellular division. Dehydration for 24 h did
      not alter calbindin-D28k mRNA expression in the SON, PVN or cingulate cortex. In
      parturient and lactating rats, calbindin-D28k mRNA levels were significantly (P <
      0.05) reduced in the medial magnocellular division of the PVN compared with
      virgin animals. No significant differences in calbindin-D28k mRNA expression were
      observed in either ventral or dorsal halves of the SON, or in the cingulate
      cortex of these animals. These results provide evidence for the differential
      expression of calbindin-D28k mRNA by hypothalamic magnocellular neurons and
      suggest that OT cells may express more calbindin-D28k mRNA than VP neurons. The
      reduction in calbindin-D28k mRNA expression by putative OT neurons of the PVN at
      the time of parturition and lactation supports the hypothesis of Li and
      colleagues (J. Physiol., 488 (1995) 601-608) that calbindin may play a part in
      determining the electrical firing patterns of magnocellular neurons. However, the
      absence of any similar decrease in the SON suggests that changes in calbindin
      D28k mRNA expression are not essential for OT neurons to exhibit episodic
      bursting behavior.

PMID- 9013785
TI  - RNAs encoded by a 3.5-kb bovine vasopressin gene construct are targeted to the
      neurohypophysis of transgenic mice.
AB  - Recent studies have established that the RNA coding for the neuropeptide arginine
      vasopressin (AVP) is expressed in the neurohypophyseal compartment of the
      hypothalamo-neurohypophyseal system. In order to determine the molecular
      mechanisms that direct this novel expression pattern we have now investigated
      whether an AVP transgene is similarly regulated. Using a reverse transcriptase
      polymerase chain reaction (RT-PCR) approach that permits simultaneous analysis of
      both endogenous and transgene RNA levels, we have demonstrated that RNA derived
      from a 3.5-kb bovine vasopressin transgene is expressed in the neurohypophysis of
      transgenic mice, and is up-regulated by a physiological stimulus (salt-loading)
      in a similar manner to mouse AVP RNA. Sequences conserved between this region of
      the murine and bovine AVP genes are therefore sufficient to mediate
      neurohypophyseal expression. These lines of transgenic mice will serve as a model
      for the delineation of sequences that target expression beyond the neuronal
      perikaryon.

PMID- 9013786
TI  - Cloning of a serine proteinase inhibitor from bovine brain: expression in the
      brain and characterization of its target proteinases.
AB  - A cDNA encoding of the serine proteinase inhibitor (serpin), B-43, was cloned
      from the cDNA library of the bovine brain. It encoded 378 amino acids, and the MW
      of the protein was estimated to be 42.6 kDa, which is consistent with that of the
      native B-43 purified from the bovine brain. The homology search revealed that B
      43 belongs to the ovalbumin branch of the serpin superfamily. Among them, B-43
      was most homologous to human placental thrombin inhibitor (PI-6) and its murine
      counterpart, with the amino acid identity of 76% and 71%, respectively. Northern
      blot analysis showed that the size of the transcript was 1.4 kb, and that the
      expression of B-43 in the bovine brain varied depending on the brain regions,
      i.e. a lower level of expression was observed in the cerebral cortex and the
      hippocampus compared to the level of expression that was observed in the medulla
      oblongata. [35S]-labeled B-43 protein was synthesized in vitro by using a rabbit
      reticulocyte lysate system, which formed complexes with proteinases such as
      thrombin, trypsin, alpha-chymotrypsin, and 7S nerve growth factor (NGF), but not
      with urokinase or plasmin. These results, together with the immunohistochemical
      localization of B-43 in astrocytes and in some neurons which was observed in the
      previous study suggest that B-43 may be involved in the regulation of serine
      proteinases present in the brain or extravasated from the blood.

PMID- 9013787
TI  - Oxytocin release is inhibited by the generation of carbon monoxide from the rat
      hypothalamus--further evidence for carbon monoxide as a neuromodulator.
AB  - Recent evidence suggests that the gas nitric oxide can modulate the secretion of
      a number of hypothalamic hormones, and may be co-localized particularly to
      oxytocin-containing neurons. Another gas, carbon monoxide (CO), has also been
      suggested to play a role in neural signaling in the brain, and the synthetic
      enzyme responsible for the generation of carbon monoxide has been reported to be
      present in the rat hypothalamus. In this study, we have therefore investigated
      whether CO has the ability to modify the release of oxytocin from acute rat
      hypothalamic explants. Hemin, a specific CO precursor through the enzyme heme
      oxygenase (the enzymatic pathway synthesizing endogenous CO, was found to inhibit
      KCl-stimulated oxytocin release, with a maximal effect at 10(-5) M, while showing
      no effect on basal oxytocin secretion. The stimulation of oxytocin by serotonin
      10 ng/ml was also significantly antagonized by hemin 10(-7) M. An inhibitor of
      heme oxygenase, zinc-protoporphyrin-9, had no effect on basal or stimulated
      oxytocin release. When hemin and zinc-protoporphyrin-9 were given together, the
      hemin-induced inhibition of oxytocin was completely antagonized by the enzyme
      inhibitor. Ferrous hemoglobin A0, a substance known to bind CO with high
      affinity, had no effect on either basal or stimulated oxytocin release, but when
      hemin and ferrous hemoglobin A0 were given together the hemin-induced inhibition
      of oxytocin was completely blocked. These findings provide evidence that
      endogenous CO may play a role in the control of oxytocin release and that, by
      analogy with nitric oxide, CO may represent a major new neuroendocrine modulator.

PMID- 9013788
TI  - The expression of MEF2 genes is implicated in CNS neuronal differentiation.
AB  - The myocyte enhancer factor-2 (MEF2) proteins are transcription factors required
      for muscle differentiation. In the present study we examined MEF2 expression in
      developing cerebellar granule neurons. In the developing postnatal cerebellum,
      RNA blot analysis revealed that MEF2A and MEF2D RNA levels increase after birth.
      The majority of this increase occurs around postnatal day 9 reaching a peak at
      postnatal day 15-18 which is maintained in adults. This time course of expression
      coincides with the expression of GABA(A) receptor alpha6 subunit RNA, a marker
      for the differentiation of the mature cerebellar granule neurons. We further
      observed, using the polyclonal antibody generated against an MEF2A peptide, that
      MEF2 protein expression occurs primarily in the internal granule cell layer of
      the developing cerebellum. Thus, MEF2 expression increases as granule neurons
      differentiate and mature. Experiments also indicated that MEF2 expression not
      only occurs in the cerebellum but also in other regions of the CNS. In adult
      mice, expression of RNA for the MEF2 isoforms A, C and D occurs throughout the
      CNS. MEF2A and D expression occurs at highest levels in the olfactory bulb,
      hippocampus and cerebellum. The expression of MEF2C differs with low levels of
      expression in the cerebellum and hindbrain. Using the MEF2A polyclonal antibody,
      we observed a similar adult pattern of expression for the MEF2 protein with high
      level of expression in the olfactory bulb, cortex, hippocampus, thalamus and
      cerebellum. These observations suggest that MEF2 molecules may be an important
      factor involved in CNS neuron differentiation similar to their role in muscle
      differentiation.

PMID- 9013789
TI  - Glutamate release correlates with brain-derived neurotrophic factor and trkB mRNA
      expression in the CA1 region of rat hippocampus.
AB  - Synthesis of the neurotrophic factor brain-derived neurotrophic factor (BDNF) and
      its receptor TrkB in the hippocampus have been proposed to be influenced by
      endogenous glutamate. To test this hypothesis we have investigated if increases
      in BDNF and trkB mRNAs are associated with changes in the synaptic release of
      glutamate in the dorsal hippocampus in the conscious rat by combining the
      technique of in vivo microdialysis with in situ hybridization histochemistry. A
      35% and 66% increase in extracellular levels of glutamate in the dorsal CA1
      region was detected following injection into the lateral entorhinal cortex of 2.4
      and 9.6 microg of the non-NMDA glutamate receptor agonist quisqualate,
      respectively. The increase in glutamate was attenuated by local administration of
      tetrodotoxin (TTX) indicating neuronal origin. Levels of BDNF and trkB mRNAs were
      increased in the hippocampus in a dose-dependent fashion following the
      stimulations. The extracellular levels of glutamate in individual animals
      correlated to the levels of BDNF and trkB mRNAs in the dorsal CA1 region of the
      hippocampus. This study provides for the first time evidence of an entorhinal
      cortex influenced concentration-dependent relationship between the release of
      endogenous glutamate in vivo and neuronal expression of mRNAs for BDNF and its
      receptor trkB in the hippocampus.

PMID- 9013790
TI  - Levels of estrogen receptor immunoreactivity are altered in behaviorally-relevant
      brain regions in female rats during pregnancy.
AB  - Pregnancy and parturition are accompanied by unique behavioral changes. Only some
      of the neural mechanisms behind the dramatic changes in behavior are understood.
      Estrogen's action within the medial preoptic nucleus (MPN) is necessary for the
      induction of maternal behavior around the time of parturition, and estrogen acts
      within the ventromedial nucleus (VMN) to trigger postpartum sexual receptivity
      shortly after parturition. We have hypothesized that the sensitivity of various
      brain regions to estrogen may be altered by pregnancy to support these unique
      behavioral patterns. Using immunocytochemistry, this study examined whether the
      levels of estrogen receptor (ER) protein, within behaviorally relevant brain
      regions, differ among females on day 8, day 16, and day 22 of pregnancy, or on
      postpartum day 1. On day 16 and day 22 of pregnancy, the MPN contained a
      significantly greater number of cells expressing high levels of ER-ir compared to
      day 8 or postpartum day 1. In the VMN, the mean amount of ER-ir per cell was
      significantly higher on day 22 of pregnancy than on day 16 or postpartum day 1.
      In the bed nucleus of the stria terminalis, ER-ir levels were significantly
      increased on postpartum day 1 compared to day 22 of pregnancy. There were no
      significant changes in ER-ir in the medial amygdala. These results demonstrate
      regionally and temporally specific regulation of ER protein in the brain during
      pregnancy. Alterations in the levels of ER at critical times in regions such as
      the MPN and VMN may underlie the unique expression of maternal and sexual
      behavior that occur during pregnancy and at the time of parturition.

PMID- 9013791
TI  - Expression of c-fos and fos-B proteins following transient forebrain ischemia:
      effect of hypothermia.
AB  - Immediate early genes are induced by transient global ischemia. Using
      immunohistochemistry we studied the effect of intraischemic hypothermia (30
      degrees C) on the expression of c-fos and fos-B proteins following 10 min
      forebrain ischemia in the gerbil. Postischemia (PI) periods of 1 hour (h), 6 h, 1
      day (d) and 2 d and nonischemic controls were examined in normothermic and
      hypothermic brains. In normothermic ischemic brains, marked expression of c-fos
      occurred in the dentate gyrus after 1 h PI which extended to CA2-4 regions by 6
      h. Hypothermia hastened the time course of c-fos expression as it was expressed
      simultaneously in the dentate gyrus as well as CA2-4 regions after only 1 h, and
      by 6 h the expression remained only in the CA2-4 regions and not the dentate
      gyrus in hypothermic ischemic brains. There was no difference in its expression
      between normothermic and hypothermic brains in the 1 d and 2 d PI animals.
      Somewhat similar changes were noted in fos-B expression. In normothermic ischemic
      brains fos-B was induced in the dentate gyrus by 1 h PI, and by 6 h it extended
      to involve CA1-4 cells. The hypothermic ischemic brains showed faster induction
      of fos-B so that the dentate gyrus as well as CA1-4 regions were immunopositive
      at 1 h PI. There was no difference in its expression between normothermic and
      hypothermic brains in the subsequent PI periods of 6 h, 1 d and 2 d. The shift
      towards faster sequential induction of these genes by hypothermia in ischemic
      brains may be indicative of preservation of or faster recovery of mechanisms
      involved in intracellular signalling.

PMID- 9013792
TI  - Developmental changes in expression of the ATBF1 transcription factor gene.
AB  - The expression of the ATBF1 gene in developing brain was analyzed in mice from 13
      days of gestation to 28 days after birth using RNase protection and in situ
      hybridization methods. The level of ATBF1 transcripts was the highest on
      embryonic day 13-15 and then progressively decreased to a hardly detectable level
      on postnatal day 28. Throughout the period examined, ATBF1 mRNA was expressed
      consistently in the basal telencephalon, diencephalon, and mesencephalon, with
      the highest levels in the inferior colliculus and thalamus. On the other hand, no
      significant expression was observed in cerebellum, neocortex, hippocampus, and
      olfactory bulb. These results illustrate significant regional differences in the
      ATBF1 expression and suggest a role of the ATBF1 gene in the formation of some
      specific cell populations in developing central nervous system.

PMID- 9013793
TI  - A bcl-2 expressing viral vector protects cortical neurons from excitotoxicity
      even when administered several hours after the toxic insult.
AB  - The product of the bcl-2 oncogene has been shown to play an important role in
      apoptosis and programmed cell death. In this study, a herpes simplex virus type-1
      vector was constructed to carry the human bcl-2 gene. The possible role of bcl-2
      in protecting neurons from excitoxicity was investigated by using the viral
      vector to deliver the gene into neuronal cultures before or after the cells were
      exposed to glutamate under conditions in which 50-80% of neurons died. Infection
      with the bcl-2 expressing vector 24 h prior to glutamate treatment effectively
      prevented the cell death that normally follows this treatment. Moreover,
      infection with the vector as late as 8 h after the glutamate insult still
      resulted in substantial neuroprotective effects. These results have potential
      implications for new therapies in stroke or ischemic neuropathies.

PMID- 9013794
TI  - Decreased NGFI-A gene expression in the hippocampus of cognitively impaired aged
      rats.
AB  - Hippocampal NGFI-A gene expression is increased following the induction of long
      term potentiation, a form of activity-dependent synaptic plasticity that has been
      implicated in learning. In this study, we show a positive correlation between
      spatial learning and the constitutive expression of NGFI-A mRNA, selectively in
      CA1 pyramidal neurons. NGFI-A mRNA expression decreased with age in CA1, CA2 and
      neocortex. Long-term amitriptyline treatment, which improved spatial learning in
      young rats, had no significant effects on NGFI-A mRNA levels. Whether hippocampal
      NGFI-A plays a direct role in the mechanism of learning and memory remains to be
      determined.

PMID- 9013795
TI  - Demonstration of the existence of mRNAs encoding N1/cif and N2/cit
      sodium/nucleoside cotransporters in rat brain.
AB  - Nucleoside transport may be involved in the regulation of extracellular levels of
      adenosine, an inhibitory neuromodulator in the central nervous system. Previous
      reports have provided functional evidence for Na+-dependent nucleoside transport
      in rat brain. We isolated total RNA from various regions of rat brain and tested
      for the presence of mRNA for two recently cloned Na+/nucleoside cotransporters
      using reverse transcriptase PCR (RT-PCR). Messenger RNA for a pyrimidine
      selective Na+/nucleoside cotransporter mRNA (rCNT1) was detected in samples from
      each brain region tested by RT-PCR amplification of a 309-bp DNA product.
      Southern blot and sequence analysis confirmed that this product was derived from
      rCNT1 mRNA. A purine-selective Na+/nucleoside cotransporter mRNA (rCNT2, also
      termed SPNT) was detected throughout brain by amplifying a 235-bp DNA product,
      the sequence of which was identical to that published. These experiments
      demonstrate the presence of both rCNT1 and rCNT2 mRNA in rat brain.

PMID- 9013796
TI  - In vitro method for assessing hepatic drug metabolism.
AB  - We investigated an in vitro metabolic test using rat liver biopsy samples by TLC
      autoradioluminography (ARLG), with a view to developing a method to rapidly
      assess the drug metabolizing activities of individual patients. Drug metabolizing
      activity was measured in liver biopsy samples collected from rats in four groups:
      a female control group, male control group, phenobarbital (PB)-administered male
      group and cimetidine (CM)-administered male group. The productivity of
      metabolites of 7-ethoxycoumarin (7-EC), debrisoquine (DB) and diazepam (DZ),
      respectively, was lower in the female control group than in the male control
      group, but there were no differences in the productivity of metabolites of 5
      fluorouracil (5-FU) and tolbutamide (TB), respectively, between the male and
      female control groups. Those of 7-EC, TB and DZ were higher in the PB
      administered group than in the male control group, but those of DB did not differ
      between these two groups. Those of 5-FU, 7-EC, TB, DB and DZ were lower in the CM
      administered group than in the male control group. Using TLC-ARLG, we could
      detect drug metabolites in rat liver biopsy samples in a relatively short time
      span at low concentrations similar to those in vivo. We could also measure drug
      metabolizing activity in cases with and without the involvement of cytochrome
      P450. When applied in clinical metabolic tests, TLC-ARLG is expected to be useful
      for assessing the drug metabolizing activities of patients.

PMID- 9013797
TI  - Photoaffinity labeling of tumor promoter-binding protein (CN-TPBP) and
      preparation of affinity sorbent gels.
AB  - Cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) was
      photoaffinity-labeled with a specific ligand, 3beta,5alpha-dihydroxycholestan-6
      one (YS-64). Analysis by ODS-HPLC of peptide fragments obtained from the labeled
      CN-TPBP by trypsinization indicated the existence of a single specifically
      labeled site. Affinity gels for the purification of CN-TPBP were then prepared.
      As ligands for the affinity gels, 12-O-tetradecanoylphorbol 13-acetate (TPA), a
      typical phorbol-type tumor promoter, and benzolactam-V8-310 (BL-V8-310), a
      structural/biological mimic of teleocidin-class tumor promoters, were adopted.
      The use of these gels afforded a protein that showed a single band of 58 kDa on
      SDS-PAGE.

PMID- 9013798
TI  - Induction of apoptosis in HeLa cells by MSSP, c-myc binding proteins.
AB  - MSSP (c-myc gene single strand binding proteins) were identified as protein
      factors binding to a putative replication origin/transcriptional enhancer
      sequence present upstream from the human c-myc gene, and two cDNAs encoding
      highly homologous proteins, MSSP-1 and MSSP-2, have been cloned. Scr2,
      independently cloned as a factor which complements the cdc2 defective mutant of
      Schizosaccharomyces pombe, has turned out to be identical to MSSP-1. MSSP-1/Scr2
      and MSSP-2 similarly stimulated the initiation of SV40 DNA replication, and thus
      were suggested to be involved in regulation of cell cycle movement, especially
      from the G1 to S phase. Here, we examined the functions of MSSP in apoptosis.
      MSSP expression plasmids were transfected to human HeLa cells together with a
      beta-galactosidase expression vector. After incubation in the presence of 2% calf
      serum, cells were stained with X-gal and morphologically apoptotic cells among
      the beta-galactosidase-positive cells were counted. Both MSSP-1 and 2 induced
      apoptosis in a dose-dependent manner as in the control experiments with c-myc or
      adenovirus E1A. DNA fragmentation, a hallmark of apoptosis, was also observed in
      cells transfected with MSSP expression plasmids. The results of experiments using
      various deletion mutants of MSSP indicated that the region containing one of the
      two RNP consensus motifs, RNP1-B, is required for induction of apoptosis as well
      as specific DNA binding activity.

PMID- 9013799
TI  - Effect of 15-hydroperoxyeicosatetraenoic acid on the fibrinolytic factor release
      and the antithrombin binding of vascular endothelial cells.
AB  - 15-Hydroperoxyeicosatetraenoic acid (15-HPETE), an arachidonate lipoxygenase
      product, is reported to induce severe endothelial injury. In this study, we
      examined the effect of 15-HPETE on the release of tissue-type plasminogen
      activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) from cultured
      human umbilical vein endothelial cells (HUVEC). The addition of 15-HPETE to the
      serum-free medium reduced the release of t-PA antigen from HUVEC, while the
      release of PAI-1 antigen was significantly enhanced. However, treatment of the
      cultured HUVEC with alpha-tocopherol or nordihydroguaiaretic acid completely
      suppressed the 15-HPETE-induced change in t-PA and PAI-1 antigen release. 15
      Hydroxyeicosatetraenoic acid (15-HETE) had no effect on the release of either
      antigen from cultured HUVEC. The HUVEC surfaces exposed to 15-HPETE decreased the
      potency for binding antithrombin III. In a reconstituted system with heparin and
      phosphatidylcholine, 15-HPETE decreased the ability of heparin to inactivate
      thrombin activity. These results suggest that the fibrinolytic factor release and
      the antithrombin binding of vascular endothelial cells are impaired by the attack
      of 15-HPETE, and that the presence of antioxidants prevents the injurious action
      of lipid hydroperoxide.

PMID- 9013800
TI  - Two molecular species of oxytocinase (L-cystine aminopeptidase) in human
      placenta: purification and characterization.
AB  - Two different forms of oxytocinase (L-cystine aminopeptidase, CAP; EC 3.4.11.3)
      were purified from the 9000 g and 105000 g precipitate fractions of human
      placenta homogenate by sequential chromatography on columns of hydroxyapatite, DE
      32, nickel ion affinity, and Sephadex G-200. One species (CAP-I) purifed from the
      mitochondrial/lysosomal fraction migrated on sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis with an apparent molecular mass of 61 kDa; the
      other (CAP-II) from the microsomal fraction was composed of two subunits with
      molecular masses of 56 and 40 kDa. The molecular masses of CAP-I and CAP-II
      estimated by gel filtration were 64 and 97 kDa, respectively. The specific
      activities of the two species for S-benzyl-L-cysteine p-nitroanilide increased by
      357- (for CAP-I) and 139-fold (for CAP-II) compared with the starting
      preparations. The optimal pH values toward the artificial substrate were approx.
      7.4-8.0 for CAP-I and 6.8-8.0 for CAP-II. The Km and Vmax values toward oxytocin
      were 5.6 microM and 23.4 micromol/h/mg protein for CAP-I, and 38 microM and 15.6
      micromol/h/mg protein for CAP-II. Both enzymes were inhibited by the metal
      chelating agents, EDTA and o-phenanthroline, whereas they were specifically
      activated by addition of Co2+: CAP-I was more sensitive to these reagents than
      CAP-II. L-Methionine strongly inhibited CAP-I, while CAP-II activity was only
      slightly affected. CAP-II was more sensitive to amastatin than CAP-I. Thus, the
      two enzymes are quite distinct in their molecular nature and biochemical
      properties. They may play a regulatory role in the metabolism of oxytocin and
      other biologically active peptides in intact placenta.

PMID- 9013801
TI  - A new method for permeabilization of the plasma membrane of cultured mammalian
      cells. VI. Enhanced cytotoxicity of bleomycin toward leukemia P388 cells
      inoculated into the tail vein of mice together with high molecular weight
      polyacrylic acid--similarity of blood stream to vortex-stirring.
AB  - Bleomycin (BLM) cytotoxicity was greatly enhanced by vortex-stirring BLM and
      mammalian cells for a few seconds together with 1 to 10 microg/ml high molecular
      weight polyacrylic acid (A-119). When suspensions of murine leukemia P388 cells
      were injected together with BLM and A-119 into the tail vein of CDF1 mice, cell
      viability was reduced to 1/1000, the reduction being similar to that obtained by
      vortex-stirring the cells with BLM and A-119 in vitro. This was corroborated by
      an increase in the survival time of these mice. The reduction in cell viability
      was noted only when the cells, BLM, and A-119 were simultaneously injected. There
      was absolutely no effect when there was a time-lag between cell inoculation and
      injection of BLM/A-119. These findings suggest that the conditions created by the
      blood stream may simulate those of vortex-stirring and that, in both cases, rapid
      uni-directional movement of cells with high molecular weight polyacrylic acid may
      affect the plasma membrane facilitating internalization of non-permeant materials
      into cells.

PMID- 9013802
TI  - Pharmacological profiles of a new antiulcer agent, SWR-215.
AB  - We investigated the effects of a new antiulcer agent, SWR-215 ([[(1,2-dihydro-2
      oxo-4-quinolinyl)methyl]thio]-N-[[[4-(1-piperidinyl methyl)-2-pyridinyl]oxy]-Z-2
      butenyl]acetamide), on histamine H2-receptors, gastric acid secretion and various
      acute experimental gastric lesions. SWR-215 showed unsurmountable histamine H2
      antagonism on isolated guinea-pig atrium. In gastric secretion studies, SWR-215
      exhibited potent and durable inhibitory effects, and the antisecretory activities
      were much stronger than that of roxatidine acetate hydrochloride (roxatidine): 5
      times stronger on basal acid secretion in pylorus ligated rats, 11 times stronger
      on histamine-stimulated acid secretion in acute fistula rats, and 2 times
      stronger on histamine stimulated acid secretion in Heidenhain-pouch dogs,
      respectively. In various experimental acute gastric lesion studies, SWR-215
      potentially inhibited almost all acute gastric and duodenal lesions compared with
      roxatidine, especially indomethacin-induced and HCl-ethanol-induced gastric
      lesions, and the inhibitory effects were exhibited at the same or lower doses
      than those which caused the antisecretory effect. Furthermore, it was considered
      that the mucosal protective effect of SWR-215 was probably unrelated to the
      endogenous prostaglandin system in gastric mucosa. These results suggest that SWR
      215 possesses both durable antisecretory and mucosal protective effects, and is
      expected to be a useful drug for the treatment of patients with peptic ulcers.

PMID- 9013803
TI  - Chronic anti-ataxic actions of the novel thyrotropin-releasing hormone (TRH)
      analog, TA-0910, during and after repeated administration in Rolling mouse
      Nagoya: behavioral and pharmacokinetic studies.
AB  - Anti-ataxic effects of TA-0910, a novel thyrotropin-releasing hormone analog, in
      mice of the ataxic mutant mouse strain Rolling mouse Nagoya (RMN) are sustained
      beyond its 2-week oral administration period (Kinoshita et al., Eur. J.
      Pharmacol., 274, 65-72, 1995). We examined the concentration of TA-0910 in the
      central nervous system (CNS) of RMN after repeated administration in an attempt
      to clarify the mechanism of the sustained effect of the drug. Repeated
      administration of TA-0910 (3 mg/kg/d, i.p.) for 2 weeks produced a long-lasting
      ameliorating effect on ataxia in RMN, and this effect was maintained until 3
      weeks after drug withdrawal. The concentrations of TA-0910 in the cerebrum and
      brain stem 24 h after the final administration were twice the concentration
      observed 24h after single administration. The cerebellum cencentration of TA-0910
      was more than 4 times that observed 24 h after final administration. After
      repeated administrations, the drug concentrations in the brain tissues gradually
      decreased, but the drug was still detectable in the cerebrum and brain stem 3
      weeks after withdrawal. However, these concentrations of TA-0910 3 weeks after
      withdrawal were as low those observed 24 h after single administration when there
      were no anti-ataxic effects. These observations suggest that the long-lasting
      ameliorating effect on the ataxia during and after repeated administration of TA
      0910 is not ascribable to the drug remaining in the CNS of RMN.

PMID- 9013804
TI  - Modification of the carcinogenic potency of quinoline, a hepatocarcinogen, by
      fluorine atom substitution: evaluation of carcinogenicity by a medium-term assay.
AB  - The potent mutagen, 5-fluoroquinoline (5-FQ), and non-mutagenic 3-fluoroquinoline
      (3-FQ) were tested for hepatocarcinogenicity using a medium-term assay system
      employing quinoline, a moderately mutagenic hepatocarcinogen, as a reference.
      F344 male rats were given a single i.p. injection of a submanifestational dose of
      diethylnitrosamine (DEN, 200 mg/kg). Then, quinoline, 3-FQ, or 5-FQ at two doses
      (0.1%, and 0.05%) was added to their diet for a period of 6 weeks, starting from
      2 weeks after the DEN injection. Control groups were administered DEN alone. All
      rats were subjected to a partial (two-thirds) hepatectomy at the end of week 3
      and sacrificed at the end of week 8. The number and areas of GST-P (placental
      glutathione S-transferase)-positive foci induced in the liver increased
      significantly as a result of treatment with 0.1% quinoline, and this increase was
      dramatic with 5-FQ at both doses, whereas no increases were noted with 3-FQ at
      either dose. Thus, the results of the medium-term carcinogenicity assay predicted
      that quinoline, a hepatocarcinogen, would be deprived of carcinogenicity by
      fluorine atom substitution at position 3, and would conversely be endowed with a
      higher carcinogenic capacity by substitution at position 5. A semi-quantitative
      relationship was demonstrated between carcinogenic and mutagenic potencies.

PMID- 9013805
TI  - Hypoglycemic effect of the rhizomes of Smilax glabra in normal and diabetic mice.
AB  - The hypoglycemic effect of the rhizomes of Smilax glabra ROXBURGH (Liliaceae) was
      investigated in normal and KK-Ay mice, one of the animal models of non-insulin
      dependent diabetes mellitus (NIDDM) with hyperinsulinemia. The methanol extract
      of rhizomes of Smilax glabra ROXBURGH (SM, 100 mg/kg body weight) reduced the
      blood glucose of normal mice 4 h after intraperitoneal administration (p<0.05),
      and also significantly lowered the blood glucose of KK-Ay mice under similar
      conditions (p<0.001). However, SM did not affect the blood glucose in
      streptozotocin-induced diabetic mice, one of the animal models of insulin
      dependent diabetes mellitus (IDDM) with hypoinsulinemia. SM also suppressed
      epinephrine-induced hyperglycemia in mice. SM-treated KK-Ay mice significantly
      decreased the blood glucose in an insulin tolerance test. We concluded that the
      hypoglycemic effect of SM raised insulin sensitivity.

PMID- 9013806
TI  - Production of plant non-protein amino acids by recombinant enzymes of sequential
      biosynthetic reactions in bacteria.
AB  - We constructed the co-expression vector, pFK4, in which two cDNAs encoding serine
      acetyltransferase (SATase) and beta-(pyrazol-1-yl)-L-alanine/L-cysteine synthase
      (beta-PA/CSase) from Citrullus vulgaris (watermelon) were over-expressed under
      the transcriptional control of T7 promoter in Escherichia coli. Accumulation of
      both SATase and beta-PA/CSase in soluble extracts of E. coli was confirmed by
      immunoblotting. The high enzymatic activities of SATase and L-cysteine synthase
      (CSase) were detected in cell-free extracts of E. coli carrying pFK4. The
      activities of the formation of beta-PA and L-mimosine, plant non-protein amino
      acids, from O-acetyl-L-serine (OAS) and the precursor heterocyclic compounds,
      pyrazole and 3,4-dihydroxypyridine, were also found in the extracts. beta-PA was
      also produced in vivo from L-serine and pyrazole as precursors by E. coli cells
      transformed with pFK4. beta-PA was accumulated mainly in the extra-cellular
      culture medium. The pronounced accumulation of L-cysteine and L-methionine was
      observed in the cells transformed with pFK4. Additionally, we also constructed
      vectors which carried chimeric genes encoding fusion proteins of SATase and beta
      PA/CSase. However, the fusion proteins tended to form insoluble inclusion bodies
      and thus to exhibit only weak enzymatic activities. The successful results of
      pFK4 shows the way to create a new sequential biosynthetic pathway of plant
      specific amino acids in bacterial cells by means of recombinant DNA technology.

PMID- 9013808
TI  - beta-Adrenoreceptor antagonistic actions and mutagenicities of R(+)- and S(-)
      enantiomers of N-desisopropylpropranolol and its N-acetyl conjugate.
AB  - Enantiospecific acetyl conjugation was examined in the rat liver 105000 x g
      supernatant (cytosol) system using racemic 1-amino-3-(1-naphthyloxy)-2-propanol
      (NDP), a N-desisopropyl metabolite of propranolol. From the results of chiral
      separative determination of the samples by HPLC using a Chiralcel OD-R column,
      more remarkable enantiospecificity was observed in the R(+)-enantiomer on NDP
      elimination and N-acetyl conjugate (AcNDP) formation. Next, the strength of beta
      adrenoceptor antagonistic actions and mutagenicities was compared between R(+)-
      and S(-)-enantiomers of NDP and AcNDP, respectively. In the case of NDP, both
      enantiomers possessed weak beta1-adrenoceptor antagonistic effects on
      isoproterenol-induced positive inotropic and chronotropic actions in the left and
      right atria isolated from a guinea pig. These actions of R(+)- and S(-)-NDP were
      1700-times and 100-times less potent, respectively, than those of propranolol.
      beta2-Adrenoceptor antagonistic actions of R(+)- and S(-)-NDP in the trachea were
      1600-times and 200-times less potent, respectively, than those of propranolol.
      Enantiospecificity was observed in the beta-adrenoceptor antagonistic action of
      S(-)-NDP, while R(+)-NDP and both enantiomers of AcNDP appeared to be negligible
      in this action. On the other hand, the mutagenicities of each enantiomer were
      examined by the Ames method using 13 kinds of Salmonella typhimurium strains. In
      the case of AcNDP, the numbers of colonies increased according to the substrate
      concentration only when rat liver 9000 x g supernatant fraction (S-9 mixture) was
      added to the plates containing TA100, YG1029, TA104 and YG3003, and then
      enantiospecificity was observed in the mutagenicity of S(-)-AcNDP. Thus, the
      ultimate mutagen might be an active metabolite formed mainly from S(-)-AcNDP.
      Despite of the addition of rat liver S-9 mixture, R(+)-AcNDP and both enantiomers
      of NDP did not indicate mutagenicity.

PMID- 9013807
TI  - In vitro skin penetration and degradation of enkephalin, elcatonin and insulin.
AB  - The work described in this paper was designed to evaluate the relevance of in
      vitro skin penetration studies of peptides across rat skin. The apparent
      penetration of three peptides, enkephalin, elcatonin and insulin, in the presence
      of enhancers was not seen in the in vitro method using Franz diffusion cells.
      However, when a protease inhibitor was mixed in the receptor fluid, the
      penetration of enkephalin and insulin was observed. Although insulin penetrated
      in the presence of enhancers, the penetration was extremely small in quantity and
      the cumulative amount did not increase with time. When the degradation of
      peptides in the receptor fluid of Franz cell was estimated, these peptides,
      especially enkephalin and insulin, were rapidly hydrolyzed and were almost
      completely lost within 3 h in the absence of an inhibitor, while elcatonin was
      slowly degraded. The addition of protease inhibitors, such as gabexate (20 mM),
      camostat (20 mM) or bile salt (taurocholate and deoxycholate, 10 mM), to the
      receptor fluid inhibited the degradation to a considerable extent, with the first
      order rate constants decreased to one-tenth compared with the constants without
      inhibitors. From the inhibitory study using specific inhibitors, it was clarified
      that enkephalin and elcatonin were mainly hydrolyzed by aminopeptidases,
      endopeptidases and serine proteases in the viable skin. Consequently, the results
      obtained from the in vitro penetration studies without inhibitors did not reflect
      reliable penetration data. Thus, effective protease inhibitor(s) should be used
      to obtain the data corresponding to the in vivo transdermal experiment. This
      methodology will provide a means to eliminate the confounding effect of
      metabolism in permeation experiments.

PMID- 9013809
TI  - Sustained release of flufenamic acid from a drug-triacetyl-beta-cyclodextrin
      complex.
AB  - Triacetyl-beta-cyclodextrin (TA-beta-CyD), a hydrophobic cyclodextrin derivative
      that is insoluble in water, was used to form a complex with flufenamic acid (FA).
      Complexes of FA with TA-beta-CyD (FA-TA-beta-CyD) at various molar ratios (1:1,
      1:2, 1:3) were prepared by a kneading method, using ethanol as a solvent. FA-TA
      beta-CyD complex formation was demonstrated by differential scanning calorimetry
      and powder X-ray diffractometry. The release rate of FA from the FA-TA-beta-CyD
      complexes was measured in both the Japanese Pharmacopoeia XII 1st fluid pH 1.2
      and isotonic phosphate buffer pH 6.8. The release rate of FA from the FA-TA-beta
      CyD complexes in the isotonic phosphate buffer pH 6.8 was significantly retarded
      compared to the release rate of FA from the FA-glucose mixture. After 1 h, 100%
      of the drug was released from the FA-glucose mixture and 10-25% was released from
      the complexes. When either the powder of the FA-glucose mixture or the FA-TA-beta
      CyD mixture was administered directly into the intraduodenal lumen in rats, the
      plasma concentration of FA reached a maximum level within 40 min after
      administration. On the other hand, when the FA-TA-beta-CyD complexes were
      administered into the intraduodenal lumen, the plasma concentration of FA did not
      show a sharp peak, but remained at a plateau level (10-18 microg/ml) for 6-8 h.
      An increased mean residence time of FA following FA-TA-beta-CyD complexes
      administration was observed; however, the AUC(0-10) for the FA-TA-beta-CyD
      complexes showed no significant difference from that for the FA-TA-beta-CyD
      mixture. These results indicate that TA-beta-CyD may serve as a hydrophobic
      carrier in sustained-release preparations of FA. The drug-TA-beta-CyD complexes
      may therefore be useful in oral administration to achieve prolonged action and
      reduced side effects.

PMID- 9013810
TI  - Purification and characterization of pranlukast hydrolase from rat liver
      microsomes: the hydrolase is identical to carboxylesterase pI 6.2.
AB  - Two carboxylesterases with pI 6.0 and 6.2 derived from rat liver microsomes were
      purified. The two isozymes were remarkably different in substrate specificity,
      but they had equal enzymatic activity for alpha-naphthyl acetate and were
      inhibited equally by phenylmethylsulfonyl fluoride (PMSF) and bis-(4-nitrophenyl)
      phosphate (BNPP). Carboxylesterases pI 6.0 and 6.2 are identical to the enzymes
      referred to as hydrolase A and B, respectively, from the results of amino acid
      sequence analyses. Pranlukast was effectively hydrolyzed by carboxylesterase pI
      6.2 but not by the pI 6.0 enzyme, and the difference in the pranlukast metabolism
      between the human and the rat could be explained by the substrate specificity of
      carboxylesterase. Furthermore, prodrugs of angiotensin converting enzyme
      inhibitors were found to be converted to the active drugs after hydrolysis by the
      carboxylesterases pI 6.0 and 6.2. Carboxylesterases generally catalyze the
      hydrolysis of ester-type drugs preferentially rather than amide-type drugs.

PMID- 9013811
TI  - Serum levels of 16-dehydropregnenolone sulfate during the early neonatal period.
AB  - We have established a method for quantifying serum 16-dehydropregnenolone (3beta
      hydroxy-5,16-pregnadien-20-one) sulfate (16-DHP S) by GC-MS. The levels of 16-DHP
      S at birth were compared in infants grouped as extremely immature (gestational
      age: 22-27 weeks), pre-term (gestational age: 28-36 weeks) and full-term
      (gestational age: 37-41 weeks). The average of the serum concentration of 16-DHP
      S in full-term infants was 0.172+/-0.104 micromol/l (n=10, mean+/-S.D.) which was
      significantly higher than the levels of the extremely immature (0.106+/-0.054
      micromol/l, n=14, p<0.05) and pre-term infants (0.088+/-0.066 micromol/l, n=33,
      p<0.01). However, 16-DHP S in sera from normal adults (age 22-73 years, n=40) was
      not detected. We investigated chronological changes in serum levels of 16-DHP S
      during the early neonatal period. In extremely immature and pre-term infants,
      these levels were significantly higher at 2-7 d than those of 16-DHP S at day 0
      (p<0.001). The levels at 8-18 d were still significantly higher than those at day
      0 (p<0.05), but in full-term infants, these levels did not change at days 0 and 2
      7. These results indicate that 16-DHP S is a steroid specific to fetuses and
      neonates and the involution of the fetal adrenal gland does not affect its serum
      levels in the early neonatal period.

PMID- 9013812
TI  - A peptide antagonist derived from platelet-derived growth factor induces
      histamine release from rat peritoneal mast cells.
AB  - A synthetic peptide (ANFLVWEIVRKKP) designed from the platelet-derived growth
      factor (PDGF) B-chain, which is known to act as a PDGF antagonist, induced
      histamine release from rat peritoneal mast cells. Maximal release by the peptide
      reached about 50% of the total histamine content in mast cells and half-maximal
      release occurred at 15 microM. The histamine release induced by the PDGF
      antagonist was required for the presence of Ca2+ in the medium. Treatment of
      kinase inhibitors (staurosporine and genistein) with mast cells before exposure
      to the PDGF antagonist inhibited the release to some extent, while calmodulin
      antagonists (W-7 and R24571) had little effect. The PDGF antagonist induced the
      secretion of actin from mast cells concurrently with histamine release, though it
      had no effect on the distribution of tubulin. These results suggest the
      possibility that PDGF and its agonists may stimulate and induce exocytosis of
      peritoneal mast cells.

PMID- 9013813
TI  - Electrophysiologic effects of nitrous oxide, a volatile anesthetic, in dogs
      following myocardial infarction in comparison with other anesthetics.
AB  - The present study was undertaken to examine the electrophysiologic effects of
      nitrous oxide in the dog heart after inducing myocardial infarction, and to
      compare these with those of other anesthetics. Myocardial infarction was produced
      by two-stage ligation of the left anterior descending coronary artery in dogs.
      Seven days after ligation, bipolar electrodes were sutured on the ventricular
      surface of the infarcted and normal regions for applying electrical stimulation
      or recording ventricular activation. Ventricular activation time and QT interval
      on the bipolar electrocardiogram and PQ interval from the standard limb lead II
      were measured during atrial pacing. Nitrous oxide 80% did not significantly
      prolong ventricular activation time, PQ interval or QT interval. However,
      halothane 1 minimum alveolar concentration (MAC), thiopental 5 and 10 mg/kg and
      fentanyl 30 microg/kg did prolong ventricular activation time; thiopental and
      fentanyl prolonged the QT interval. Nitrous oxide did not potentiate the effects
      of fentanyl. Therefore, electrophysiologic effects of nitrous oxide are much
      weaker compared with those of thiopental, fentanyl or halothane.

PMID- 9013814
TI  - Distribution of thyrotropin-releasing hormone (TRH) receptors in the brain of the
      ataxic mutant mouse, rolling mouse Nagoya.
AB  - Thyrotropin-releasing hormone (TRH) and its analog, TA-0910, ameliorate the
      ataxia of the mutant mouse, rolling mouse Nagoya, by metabolic normalization in
      the ventral tegmental field (VTF). We here investigated the distribution of
      cerebral TRH receptors in the rolling mouse to clarify the sites of action of
      these drugs. TRH receptors were widely distributed in multiple brain areas,
      including in the VTF and the cuneiform nucleus (CnF) which terminates in the VTF.
      These results suggest that TRH and TA-0910 directly activate the VTF by acting on
      TRH receptors in the VTF and indirectly activate it through the receptors in the
      CnF.

PMID- 9013815
TI  - Effect of pilocarpine on striatal acetylcholine release in dopamine-depleted
      rats.
AB  - We have previously demonstrated that the systemic administration of pilocarpine
      stimulates striatal acetylcholine (ACh) release in rats using a brain
      microdialysis technique. In the present study, we investigated whether a nigro
      striatal dopaminergic system is involved in the pilocarpine-induced increase in
      striatal ACh release using dopamine-depleted rats under urethane anesthesia. The
      application of pilocarpine (0.1-10 mM) via the microdialysis tube increased
      striatal ACh release in normal rats in a concentration-dependent manner, but it
      had no effect on the release of glutamate or gamma-aminobutyric acid (GABA) from
      the striatum. The increase in striatal ACh release caused by pilocarpine (1 mM)
      was enhanced by reserpine and alpha-methyl-p-tyrosine treatment, which completely
      depleted dopamine in the striatum. These results suggest that pilocarpine
      selectively increases striatal ACh release by acting at the striatum, and that
      the nigro-striatal dopaminergic neurons play an inhibitory role in the
      pilocarpine-induced ACh release.

PMID- 9013816
TI  - Reduction in blood free carnitine levels in association with changes in sodium
      valproate (VPA) disposition in epileptic patients treated with VPA and other anti
      epileptic drugs.
AB  - Reduction in the blood free carnitine (FC) level as a side effect of sodium
      valproate (VPA) given epileptic patients was pharmacokinetically studied in
      connection with changes in the VPA disposition. The serum FC level in patients
      taking at least one of phenobarbital (PB), phenytoin (PHT) and/or carbamazepine
      (CBZ) in addition to VPA was significantly lower than that in the controls given
      only these other anti-epileptic drugs (AEDs). Patients medicated only with VPA
      also tended to have a lower serum FC level than the controls, although the
      difference was not significant. Among all the patients taking VPA with or without
      other AED(s), a significantly positive correlation was observed between the serum
      FC level and the value of dose and level ratio (L/D) of VPA, indicating that both
      the serum FC concentration and the L/D value of VPA were remarkably reduced in
      those patients receiving both medications. These results suggested that reduction
      in the blood FC level as a side effect of VPA reflected FC deficiency associated
      with the accelerated degradation of VPA in liver; such a condition appears to
      result from medication with VPA and other AED(s) which induce(s) enzyme(s) for
      the VPA metabolism.

PMID- 9013817
TI  - Relationship between the metabolic chiral inversion and chemical structure of 4
      phenyl-4-oxobutanoic acids, derivatives of anti-rheumatic agent KE-298.
AB  - The relationship between metabolic chiral inversion and chemical structure of
      various 4-phenyl-4-oxobutanoic acids (4-OBA), derivatives of anti-rheumatic agent
      KE-298 [2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid], was
      investigated in rats. Chiral inversion occurred with the thio-alkyl group,
      whereas the thio-acyl group played no role in the inversion of 4-OBA. A 2
      methylene moiety was required for the inversion. When the 4-carbonyl moiety was
      removed, chiral inversion was significantly decreased, which provided an affinity
      for the intramitochondrial medium chain fatty acid CoA ligase. In addition, the
      distance between the chiral center and the carbonyl moiety was also an important
      factor for chiral inversion. While a sulfur atom was not indispensable for the
      chiral inversion, the existence of the sulfur atom influenced its affinity to the
      long chain fatty acid CoA ligase.

PMID- 9013818
TI  - Analysis of mitogenic substances in Bupleurum chinense by ESR spectroscopy.
AB  - The polyphenolic substance(s) in the hot water extract of Bupleurum chinense
      (PSF) showed strong mitogenic activity. In this paper, we analyzed PSF by using
      ESR spectroscopy, and found that i) PSF showed a strong ESR signal on g = 2.005
      which was similar to the commercially available lignin; ii) Sho-saiko-to, which
      contains an extract of B. chinense, also showed similar signals on ESR; iii)
      Powdered B. chinense also showed similar signals on g = 2.005. Peroxidase
      activity, essential for producing polyphenolic substances, was detected in the
      cold water extract of B. chinense. In addition, the signal intensity of the ESR
      spectrum of B. chinense was increased after boiling. The data of the ESR spectra
      of the model reactions using lignin, arginine, proline and maltose also strongly
      suggested that a certain chemical modification proceeded during the hot water
      extraction to increase the percentage of the stable free radical. These facts
      strongly suggested that the mitogenic substance in B. chinense is a polyphenolic
      substance extracted by hot water, and the structure was modified during the
      extraction to increase the stable free radical components.

PMID- 9013819
TI  - An enzyme immunoassay for prostaglandin E2 using biotin-prostaglandin B2
      conjugate as a tracer.
AB  - Prostaglandin E2 (PGE2) was converted into prostaglandin B2 (PGB2) by alkaline
      treatment and quantitated by a novel and specific competitive enzyme immunoassay
      using an anti-PGB2 antibody and a biotin-PGB2 conjugate as a tracer. This assay
      was relatively specific for PGE1 and PGE2 (n-6 type); the reactivity for PGE3 (n
      3 type) was below 2% of that for n-6 type, and was applicable to the quantitation
      of PGE2 synthesized in lipopolysaccharide-stimulated peritoneal macrophages from
      mice fed either a high linoleate or a high alpha-linolenate diet.

PMID- 9013820
TI  - Enhanced myopathy following administration of hypolipidemic agents under urethane
      anesthesia.
AB  - The enhanced effect of urethane anesthesia on the serum creatine kinase (CPK)
      level following administration of hypolipidemic agents was examined to develop a
      convenient experimental screening method for drug-induced myopathy. After oral
      administration of a hypolipidemic agent to rats, 25% urethane solution was
      infused intravenously at a very low rate using a microinfusion pump. Blood
      samples were collected 7 h after drug administration and the risk of myopathy was
      evaluated based on the CPK level. When bezafibrate (BF), simvastatin (SV), or
      pravastatin (PV) (50-500 mg/kg) was orally administered under urethane infusion,
      enhanced elevation of the serum CPK level was observed dose dependently for BF
      and SV, but not for PV. The elevation of serum CPK was much higher with BF than
      with SV or PV. In addition, when SV or PV (50-500 mg/kg) was coadministered with
      50 mg/kg of BF, there was a striking increase in the serum CPK level as compared
      with the drug alone. Without urethane infusion, no significant elevation in serum
      CPK level was observed even at a high dose of these hypolipidemic agents. These
      phenomena suggest that the urethane anesthesia enhanced the elevation of the
      serum CPK level following administration of hypolipidemic agents. We propose that
      this method is a simple and speedy screening test for drug-induced myopathy.

PMID- 9013822
TI  - Molecular cloning of the nemA gene encoding N-ethylmaleimide reductase from
      Escherichia coli.
AB  - Using the gene mapping membrane technique, we identified a gene (nemA) that
      encodes N-ethylmaleimide reductase in Escherichia coli. The open reading frame
      encodes a polypeptide of 365 amino acids with a molecular mass of 39,514 Da. The
      deduced amino acid sequence showed a high degree of homology (87% identical) with
      the pentaerythritol tetranitrate reductase of Enterobacter cloacae and the
      morphinone reductase of Pseudomonas putida (52% identical).

PMID- 9013821
TI  - Phenylmercury transport mediated by merT-merP genes of Pseudomonas K-62 plasmid
      pMR26.
AB  - The merB-merA-deleted plasmid pMRD141 which contains the intact merT-merP genes
      of pMRA17 conferred bacterial hypersensitivity not only to Hg2+ but also to
      C6H5Hg+. The bacterium with pMRD141 took up significantly more C6H5Hg+ than its
      isogenic strain with the cloning vector Bluescript II. The hypersensitivity to
      C6H5Hg+ seems to be based on hyperaccumulation of toxic C6H5Hg+ in the absence of
      detoxifying enzymes encoded by merB and merA. Our results show that bacterial
      transport of C6H5Hg+ into the cytoplasm is regulated by merT-merP genes.

PMID- 9013823
TI  - Telepathology: a ten-year progress report.

PMID- 9013824
TI  - Dynamic-robotic telepathology: Department of Veterans Affairs feasibility study.
AB  - In this retrospective study, we assess the accuracy, confidence levels, and
      viewing times of two generalist pathologists using both dynamic-robotic
      telepathology and conventional light microscopy (LM) to render diagnoses on a
      test set of 100 consecutive routine surgical pathology cases. The objective is to
      determine whether telepathology will allow a pathology group practice at a
      diagnostic hub to provide routine diagnostic services to a remote hospital
      without an on-site pathologist. For TP, glass slides were placed on the motorized
      stage of the robotic microscope of a telepathology system by a senior laboratory
      technologist in Iron Mountain, MI. Real-time control of the motorized microscope
      was then transferred to a pathologist in Milwaukee, WI, who viewed images of the
      glass slides on a video monitor. The telepathologists deferred rendering a
      diagnosis in 1.5% of cases. Clinically important concordance between the
      individual diagnoses rendered by telepathology and the "truth" diagnoses
      established by rereview of glass slides was 98.5%. In the telepathology mode,
      there were five incorrect diagnoses out of a total of 197 diagnoses. In four
      cases in which the telepathology diagnosis was incorrect, the pathologist's
      diagnosis by LM was identical to that rendered by telepathology. These represent
      errors of interpretation and cannot be ascribed to telepathology. The certainty
      of the pathologists with respect to their diagnoses was evaluated over time.
      Results for the first 50 cases served as baseline data. For the second 50 cases,
      confidence in rendering a diagnosis in the telepathology mode was essentially
      identical to that of making a diagnosis in the LM viewing mode. Viewing times in
      the telepathology mode also improved with more experience using the telepathology
      system. These results support the concept that an off-site pathologist using
      dynamic-robotic telepathology can substitute for an on-site pathologist as a
      service provider.

PMID- 9013825
TI  - Transcontinental consults in surgical pathology via the Internet.
AB  - An efficient and inexpensive electronic system to submit surgical pathology cases
      in consultation via the Internet is presented. A transcontinental pilot study
      showed a high degree of concordance between the diagnosis provided by the
      consultant on the basis of the pathology images and that given after examining
      the corresponding microscopic slides.

PMID- 9013826
TI  - Diagnostic accuracy of an international static-imaging telepathology consultation
      service.
AB  - Static-image and dynamic- (real-time) image telepathology are competing
      technologies. Although some studies suggest that the diagnostic accuracy of the
      dynamic-image telepathology approaches the accuracy of light microscopy, few
      reports have documented the diagnostic accuracy of static-image telepathology as
      used in the setting of an actual surgical pathology consultation practice. We
      report the results of an analysis of 171 telepathology consultation cases
      submitted to the Arizona-International Telemedicine Network (AITN). Digital
      images were submitted by pathologists from six participating institutions in
      Arizona, Mexico, and China. Telepathologists could render a telepathology
      diagnosis (TP) or defer rendering a diagnosis to obtain additional video images,
      glass slides for detailed analysis, or to obtain tissue blocks for special
      studies such as immunohistochemistry. The telepathologists rendered diagnoses for
      144 cases and deferred 27 cases. Two pathologists retrospectively evaluated-glass
      slides from each case and rendered a consensus glass slide (GS) "truth"
      diagnosis. There was 88.2% concordance between TP and GS diagnoses (127 of 144
      diagnoses). Concordance of 96.5% was achieved for clinically important diagnoses
      (139 of 144 diagnoses). Telepathologists deferred making a diagnosis to obtain
      glass slides for conventional light microscopy in 14 cases (8.1%) and for results
      of immunohistochemistry studies in 13 cases (7.6%). Thus, correct diagnoses were
      rendered by static-image telepathology in 127 of 171 cases (74.3%) at the time of
      telepathology diagnostic sessions. Inappropriate field selection and sampling
      biases of referring pathologists, as well as a tendency of static-image
      telepathologists to underestimate the complexity of some cases, may reduce the
      value of consultations based on the viewing of static images.

PMID- 9013827
TI  - Telepathology diagnosis of prostrate needle biopsies.
AB  - We conducted a prospective analysis of the diagnostic accuracy of a static-image
      telepathology system (Roche RIAS, Elon College, NC) in the interpretation of
      needle biopsies of the prostate (NBx). Two hundred consecutive cases received in
      consultation were included. Each case was examined by one of the researchers
      (MHW), and images were captured either according to the areas of concern
      designated by the referring pathologist (set A; 100 cases) or according to the
      judgment of MHW (set B; 100 cases). The other researcher (JIE) daily rendered
      diagnoses first on the video images and then by direct microscopy. Accuracy of
      video diagnosis was categorized as 0 (correct), 1 (minor error), 2 (major error),
      or 3 (deferred). An average of 5.49 images were captured per case in set A, and
      5.28 for set B. Seventy-seven, 9, 9, and 5 cases were categorized as 0, 1, 2, and
      3, respectively, for set A, and 78, 17, 1, and 4 cases, respectively, for set B.
      Video versus direct diagnoses for the type 2 errors were five carcinoma versus
      markedly atypical, two carcinoma versus atypical, one carcinoma versus
      nonspecific granulomatous prostatitis, and two benign versus atypical. In these
      difficult NBx, telepathology allowed an essentially correct diagnosis in almost
      all of the cases. The number of images required was reasonable, and the images
      were of excellent quality. However, the accuracy varied from set A to set B, with
      the fractions of nondeferred cases that were given an essentially correct video
      diagnosis totaling 91% and 99%, respectively (P < .01). Accuracy of telepathology
      diagnosis using static images may depend on the person capturing the images, even
      in the case of small biopsies.

PMID- 9013828
TI  - Static image analysis of skin specimens: the application of telepathology to
      frozen section evaluation.
AB  - Although the ability to transmit high-resolution images of histopathological
      sections could have a profound impact on the practice of pathology, the
      application of video microscopy to the daily activities of surgical pathology has
      not been rigorously evaluated. In particular, certain aspects of video microscopy
      relating to frozen section evaluation have not been adequately assessed. We
      conducted a retrospective analysis of 48 excisional skin biopsy specimens
      encompassing a spectrum of benign and malignant lesions. To simulate an actual
      frozen section evaluation, only original frozen section slides were evaluated.
      Fields were selected and digitized (Roche Image Analysis System) by a pathology
      resident. Two sets of diagnoses were subsequently rendered by a surgical
      pathologist, the first set based on the digitized images and the second based on
      direct microscopic examination of the histological slides. The two sets of
      diagnoses were compared, and the concordance rates were as follows: malignant
      diagnoses, 100%; benign diagnoses, 100%; positive margins, 96%; negative margins,
      99%. One (4%) of the 25 positive margins was indexed as negative by image
      analysis. Conversely, one (1%) of the 121 negative margins was indexed as
      positive by image analysis. In both of these cases, error was attributable to
      selection and digitization of an inappropriate field. We conclude that
      telepathology of static images is an accurate method of evaluating frozen
      sections of skin lesions. Potentially, this technology could be applied to the
      frozen section evaluation of other lesions as well. Static image analysis is,
      however, susceptible to errors induced by inappropriate field selection,
      emphasizing the need for trained and skillful personnel on both sides of the
      video camera.

PMID- 9013829
TI  - Color images in telepathology: how many colors do we need?
AB  - It is generally assumed that for telepathology, accurate depiction of microscopic
      images requires the use of "true color" (ie, 24 bits, eight bits each for red,
      green, and blue) in the digitized image used for transmission. If such a 24-bit
      color image file, which provides a palette of 16.7 million colors, could be
      reduced in size by decreasing the possible numbers of colors displayed in the
      image to 8 bits (palette of 256 colors), the image files would require less
      storage space, could be transmitted more rapidly, and would require less
      telecommunications bandwidth. However, such color reduction must not result in
      detectable image degradation, especially if the images are to be used for
      diagnosis. Therefore, we performed a carefully controlled study to determine
      whether pathologists could detect differences in the quality of microscopic
      images that were reduced from 24 to 8 bits of color. Thirty pathologists were
      each asked to view a set of 30 image pairs displayed on a computer monitor. Each
      image pair consisted of the original 24-bit color version and an 8-bit color
      reduced version, derived using an adaptive color reduction algorithm with
      diffusion dithering. Observers were asked whether they could detect any
      difference in quality between the image pairs. Then, regardless of their answer,
      they were asked to choose the better quality image of the pair. Overall, there
      was not a statistically significant ability to consciously detect differences
      between the image pairs (P < .750). However, when forced to choose, there was a
      significant preference for the 8-bit images as being of "better quality" (P <
      .005). We conclude that telepathology applications may be able to take advantage
      of adaptive color reduction algorithms to reduce image file size without
      sacrificing image quality. Additional studies must be performed to determine the
      minimal image requirements for accurate diagnosis by telepatholgy.

PMID- 9013830
TI  - Marginal zone B-cell lymphomas: an appraisal.
AB  - Although the Revised European-American Lymphoma Classification does not utilize
      the term monocytoid B-cell Lymphoma, there are numerous reasons to support its
      use in classifying lymphomas of so-called marginal zone B-cell type that contain
      a distinct population of malignant monocytoid B-cells. In addition, there are
      other B-cell lymphomas which have very distinctive morphological features,
      because they show multiple and very well demarcated histologies characterized by
      presence of cells that appear to be (1) malignant monocytoid B-cells and
      malignant follicular center cells, or (2) malignant monocytoid B-cells, malignant
      follicular center cells and malignant plasma cells, or (3) malignant monocytoid B
      cells and malignant mantle cells. The neoplastic cells in each of the above three
      examples show identical light chain restriction and thus they are part of the
      same neoplastic clone. We believe that there are different types of precursor B
      cells (memory or otherwise) for the above cells, and an arrest in differentiation
      of these precursor B-cells may readily explain the presence of these different
      morphological combinations. Recognition of these morphological types may lead to
      further awareness of the possibilities of the existence of multiple, linked
      pathways of differentiation for lymphoid cells including the possibility of
      different types of precursor B-cells. Furthermore, an understanding of the
      uniqueness of monocytoid B-cells would allow pathologists to use terminology that
      is less redundant and more precise.

PMID- 9013831
TI  - The oncocytic variant of papillary carcinoma of the thyroid: a clinicopathologic
      study of 15 cases.
AB  - The oncocytic variant of papillary carcinoma of the thyroid represents an unusual
      neoplasm whose clinicopathological features and biological behavior have not been
      thoroughly characterized. We studied 15 cases of thyroid tumors predominantly
      composed of oncocytic (oxyphilic) cells that were characterized by showing the
      classical nuclear features of papillary carcinoma of the thyroid. Thirteen
      patients were women, and two were men; their ages ranged from 34 to 86 years. The
      tumors measured from 1 to 4 cm in diameter and were well circumscribed and
      confined to the thyroid gland in all cases except for one, in whom there was
      extrathyroidal local extension. Histologically, all tumors showed, at least
      focally, the formation of papillary structures; in 13 cases the papillary
      features were found to predominate or were admixed in equal proportion with a
      follicular pattern of growth, and in two the follicular growth pattern
      predominated and only abortive, small papillary structures could be found on
      extensive search. In all cases, the classical optically clear nuclei of papillary
      carcinoma were present throughout the lesions. Nuclear grooves and intranuclear
      cytoplasmic inclusions were also a prominent and constant component of these
      lesions. In 13 cases, the tumors showed the features of Hashimoto's or
      lymphocytic thyroiditis in the surrounding, uninvolved thyroid parenchyma. Follow
      up of 1.2 to 13 years (median, 4.5 years) showed the development of cervical
      lymph node metastases 9 months after surgery in one case; the remainder of
      patients were alive and free of disease. Oncocytic papillary carcinoma seems to
      represent a distinctive morphological variant of carcinoma of the thyroid that in
      our experience does not appear to behave more aggressively than conventional
      papillary carcinoma. The frequent association of these tumors with autoimmune
      thyroiditis raises the possibility that the oncocytic changes may be
      pathogenetically related with the latter process. These tumors should be
      distinguished from benign and malignant Hurthle cell tumors and other oncocytic
      thyroid neoplasms that may follow a different biological behavior.

PMID- 9013832
TI  - Extracellular matrix expression in metastasizing and nonmetastasizing
      adenocarcinomas of the lung.
AB  - Alterations in extracellular matrix, cell-cell and cell-matrix adhesion, and
      oncogenes are thought to be important in tumor progression and metastasis.
      Adenocarcinomas of the lung from 31 patients were studied for immunohistochemical
      expression of basement membrane molecule type IV collagen, type IV collagenase,
      and integrins alpha2,3,v adhesion molecules to assess their diagnostic and
      prognostic importance in pathological stage T2 tumors. The results indicate that
      with decreasing tumor differentiation, there is a progressive loss of type IV
      basement membrane collagen (P = .06) and decreased integrin alpha2 expression (P
      = .03). Type IV collagenase expression was significantly associated with the
      presence of lymph node metastases, with moderate to strong expression present in
      53% T2N1 tumors compared with none (0%) of the T2N0 tumors (P = .008). Integrin
      alpha(v) was increased in tumors with nodal metastases compared with those
      without (P = .08). Loss of alpha2 and alpha3 integrins was associated with
      increased alpha v expression (P = .03). Median survival was 48 months for T2N0
      and 20 months for T2N1 (P = .07). In correlating expression of the
      immunohistochemical markers and survival, type IV collagenase expression was
      found to be a predictor of survival at a level of P = .07. Measurable alterations
      in integrins and extracellular matrix, and in particular, expression of matrix
      degrading enzyme type IV collagenase may be of prognostic importance in
      resectable adenocarcinoma of the lung.

PMID- 9013833
TI  - Immunohistochemical localization of p21(WAF1/CIP1) in normal, hyperplastic, and
      neoplastic uterine tissues.
AB  - p21WAF1/CIP1 is a nuclear protein that binds to cyclin-dependent kinase complexes
      (CDKs) and inhibits the activity of multiple kinases. These CDKs are involved in
      the regulation of cell cycle progression at several checkpoints. In this study,
      the authors have analyzed by immunohistochemistry the expression of p21WAF1/CIP1
      in normal uterine tissues, 12 endometrial hyperplasias, 17 endocervical
      adenocarcinomas, and 31 endometrial adenocarcinomas. In addition, a group of 10
      leiomyomas and 10 uterine leiomyosarcomas were also stained. To evaluate cell
      proliferation, the monoclonal antibody Ki-67 was used in all of the available
      cases. Terminally differentiated epithelial endocervical and endometrial cells
      showed variable expression of p21WAF1/CIP1, whereas the endometrial hyperplasias,
      and endocervical and endometrial adenocarcinomas showed decreased expression or
      were negative. All of the cases of cervical squamous dysplasia were positive.
      Normal smooth muscle cells and 50% of leiomyomas were negative, whereas all
      leiomyosarcomas showed expression of p21WAF1/CIP1. These results indicate that
      p21WAF1/CIP1 contributes to differentiation in normal endometrial and
      endocervical glands. The decreased expression of p21WAF1/CIP1 in endometrial
      hyperplasias and carcinomas may be important in the process of neoplastic
      transformation. The role of certain CDK inhibitors, such as p21WAF1/CIP1, is
      different in epithelial and mesenchymal tumorigenesis in the uterus.

PMID- 9013834
TI  - Subacute cutaneous lupus erythematosus arising in the setting of calcium channel
      blocker therapy.
AB  - After 6 months to 5 years of calcium channel blocker (CCB) therapy for arterial
      hypertension, nine patients developed photoinduced annular or papulosquamous
      eruptions consonant clinically with subacute cutaneous lupus erythematosus
      (SCLE). Four patients were receiving diltiazem, four received verapamil, and one
      was taking nifedipine. Serology showed antinuclear antibodies (ANA) in seven of
      nine patients, anti-Ro antibodies in five, and anti-La antibodies in five, with
      three patients having only anti-La antibodies. Skin biopsy specimens in all nine
      patients were held to be characteristic of SCLE based on light microscopy,
      direct, and indirect immunofluorescence. The CCB was discontinued in all; in 8
      patients in whom the CCB was stopped, the eruption resolved. A proposed mechanism
      by which the CCBs may have precipitated the eruptions is offered.

PMID- 9013835
TI  - Significance of the expression of proliferation-associated nucleolar antigen p120
      in human colorectal tumors.
AB  - Nucleolar protein p120 is considered to be associated with cell proliferation and
      has also been detected in a broad range of human malignant cells and tissues, but
      not in either normal resting tissue or most benign tumors. To clarify the
      significance of the expression of p120 in colorectal tumors or to evaluate the
      contribution of p120 in the development of colorectal carcinoma, the authors
      developed a monoclonal antibody against p120 and then examined its expression in
      adenoma, carcinoma, and normal mucosa. In adenomas, p120 expression was shown in
      none of 13 cases of mild dysplasia (0%), 2 of 15 of moderate dysplasia (13.3%),
      and in 2 cases of severe dysplasia (100%). p120-positive adenomas of moderate
      dysplasia tended to be larger and had higher Ki-67 indexes than the negative ones
      (adenomas of moderate dysplasia). All 27 carcinomas were positive for p120. p120
      immunostaining was found in the nuclei and corresponded closely to the prominent
      nucleoli of tumor cells. In contrast, either weak or the occasional expression of
      p120 was traced in only one of the nine normal mucosae (11.1%). Three of the
      transitional mucosae of the carcinoma were also positive for p120. The percentage
      of p120-positive tumor cells (p120 index) ranged from 3.2% to 86.6%, and the mean
      p120 indexes of the four adenomas and all carcinomas were 21.3% and 41.5%,
      respectively. The p120 index was significantly related to the Ki-67 index (P <
      .001) in the p120-positive tumors, whereas the p120 index of the carcinoma did
      not significantly correlate to the known prognostic markers, such as tumor size,
      stage, or the degree of differentiation. These results thus suggest that the
      expression of p120 serves as a marker for cells with a high proliferative
      potential and is linked to the late events of colorectal tumor progression.

PMID- 9013836
TI  - KRAS oncogene mutations suggest a common histogenetic origin for pleomorphic
      giant cell tumor of the pancreas, osteoclastoma of the pancreas, and pancreatic
      duct adenocarcinoma.
AB  - Giant cell neoplasms of the pancreas are rare tumors of uncertain histogenesis.
      Mutation of the KRAS oncogene is common in typical pancreatic duct
      adenocarcinoma. We have analyzed DNA from five pancreatic tumors with giant cells
      for mutations in the KRAS oncogene and found alterations of the second position
      of codon 12 in each case (four G > A transitions and one G > C transversion). The
      common mutation pattern in tumors with giant cells and duct adenocarcinoma
      suggests a common route to malignant transformation and may indicate a shared
      histogenesis. We also tested 11 cases of malignant fibrous histiocytoma, a
      histological mimic of pleomorphic giant cell tumor, for mutations in the KRAS
      oncogene. The absence of KAS mutations in each of the malignant fibrous
      histiocytomas (MFHs) and in other histologically similar tumors may provide
      assistance in the differential diagnosis of pleomorphic pancreatic tumors.

PMID- 9013837
TI  - Pleural mesotheliomas have an integrin profile distinct from visceral carcinomas.
AB  - Cryosections of epithelial, sarcomatoid, and biphasic malignant mesotheliomas
      (EMM, n = 11; SMM, n = 5; BMM, n = 6) of the pleura were immunostained with
      monoclonal antibodies to integrin subunits alpha 1-6 and v, and beta 1-4.
      Localization patterns were compared with those known to occur in pulmonary and
      other adenocarcinomas (PADC, ADC). EMM and the epithelial component of BMM
      (ecBMM) expressed alpha 1,3,5,6, and v and beta 1 and 4. SMM and the sarcomatoid
      elements of BMM (scBMM) reacted variably for alpha 1,3,5,6 and v, and beta1.
      Reactions for alpha3, found in all tumors, were strongest in EMM, ecBMM, and
      PADC. Our findings indicate that EMM and ecBMM parallel PADC and most ADC in
      their expression of alpha6 beta4, underscoring that this laminin integrin
      receptor is intimately associated with these neoplastic epithelial phenotypes.
      Also, our observations on alpha3 beta1 suggest that this cell-cell adhesion
      mediating integrin is related to the epithelial phenotype. Notably, all malignant
      mesotheliomas (MM), including those with distinct glandular structures, expressed
      the alpha5 beta1 fibronectin receptor, thus paralleling most sarcomas and
      differing from PADC and most other ADC. We conclude that irrespective of
      architectural and cytologic variants, transformed mesothelial cells possess an
      integrin repertory that differs significantly from that of most ADC, including
      those of the lung. These findings set mesothelium apart from epithelia and may
      prove helpful as adjunct tools for the differential diagnosis between EMM and AD.

PMID- 9013838
TI  - Is immunostaining with HAM56 antibody useful in identifying ovarian origin of
      metastatic adenocarcinomas?
AB  - HAM56 (human alveolar macrophage) is a monoclonal antibody that reacts with
      macrophages and endothelial cells. There has been controversy as to its
      usefulness in differentiating adenocarcinomas of ovarian or gastrointestinal
      origin. The aim of this study is to test the specificity of HAM56 in identifying
      the origin of metastatic adenocarcinomas. Ninety-two adenocarcinomas of known
      primary site, metastatic to omentum or lymph nodes were used. Immunostaining for
      HAM56 was performed on formalin-fixed, paraffin-embedded tissue after antigen
      retrieval with microwave pretreatment. Positive immunostaining was shown as
      membrane or cytoplasmic staining with luminal accentuation. Nonspecific staining
      in necrotic debris or mucin was excluded. Immunoreactivity for HAM56 was found in
      37 metastatic adenocarcinomas; 22 of 31 cases (71%) of ovarian origin, 7 of 33
      (21%) of colonic origin, 4 of 16 (25%) of gastric origin, 3 of 6 (50%) of biliary
      origin; and 1 of uterine origin (100%). Negative staining was found in
      adenocarcinomas from the pancreas (n = 2), cervix (n = 2), and fallopian tube (n
      = 1). These findings suggest that HAM56 reacts with adenocarcinomas arising from
      several origins though with a higher frequency in ovarian tumors. It is thus not
      specific for ovarian carcinomas and is, therefore, not a useful tool to help
      distinguish adenocarcinomas of unknown origin.

PMID- 9013839
TI  - The influence of fixation delay on mitotic activity and flow cytometric cell
      cycle variables.
AB  - Proliferation variables such as mitotic activity and the percentage of S-phase
      cells have been shown to be of prognostic value in many tumors, especially in
      breast cancer. However, some studies reported a decrease in mitotic activity
      caused by delay in fixation of the tissue. In contrast, other studies showed that
      the identifiability of mitotic figures decreases after fixation delay, but the
      total number of mitotic figures and also the percentage of S-phase cells remain
      unchanged. Most studies have been done on small numbers of experimental tumors,
      thus introducing the risk of selection bias. The aim of this study was to
      reinvestigate the influence of fixation delay on mitotic activity and cell cycle
      variables assessed by flow cytometry in an adequate number of resected human
      tissues to reach firmer conclusions. Resection specimens of 19 and 21 cases,
      respectively, for the mitotic activity estimate and the flow cytometric
      percentage of S-phase calculation were collected directly from the operating
      theater using lung, breast, and intestinal cancers and normal intestinal mucosa.
      The tissues were cut in pieces, and from each specimen, pieces were fixed in 4%
      buffered formaldehyde (for mitosis counting) as well as snap frozen (for flow
      cytometry) immediately after excision, as well as after a fixation delay of 1, 2,
      4, 6, 8, 18, and 24 hours. Moreover, during the fixation delay, one series from
      each specimen was kept in the refrigerator and the second at room temperature.
      Thus, a total of 304 (19 X 16) and 336 (21 X 16) specimens were investigated for
      the mitotic activity estimate and the percentage of S-phase cells calculation,
      respectively. With regard to the estimation of the mitotic activity, both clear
      and doubtful mitotic figures were registered separately, obtaining an
      "uncorrected" and "corrected" (for doubtful mitotic figures) mitotic activity
      estimate. The percentage of S-phase cells was obtained by cell cycle analysis of
      flow cytometric DNA-histograms. The results showed that the quality of the
      material decreased during the fixation delay, as reflected by poorer cellular
      morphology in the hematoxylin-and-eosin-stained slides, resulting in more
      difficult identification of mitotic figures and a more time-consuming procedure
      with regard to the mitosis counts, but not in a worse intraobserver and
      interobserver reproducibility, which was acceptable. The reduction in quality of
      the tissues also was shown by the flow cytometric measurements because the
      coefficient of variation and percentage of debris increased after 4 hours or more
      of fixation delay. However, the mean values of the "uncorrected" mitotic activity
      and the "corrected" mitotic activity showed no decreasing trend; neither did the
      average percentage of S-phase cells. In conclusion, within the time investigated,
      fixation delay has no clear influence on the proliferation features studied.
      Because of the decreasing quality of the histological sections, resulting in more
      difficult identification of mitoses and interpretation of DNA histograms,
      fixation delay should be kept as short as possible, keeping the tissue at 4
      degrees C until fixation.

PMID- 9013840
TI  - Primary effusion Burkitt's lymphoma with t(8;22) in a patient with hepatitis C
      virus-related cirrhosis.
AB  - Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma
      through yet unknown pathogenetic mechanisms. We describe the case of a patient
      with HCV-related cirrhosis who developed a primary effusion lymphoma (PEL) of
      Burkitt's type confined to the peritoneal cavity, in the absence of
      immunodeficiency or autoimmunity. Paracentesis followed by immunophenotyping,
      karyotyping, and molecular studies allowed us to diagnose a small noncleaved B
      cell lymphoma (CD20+, CD24+, CD10+, CD5-, CD23-, lambda+) with the t(8;22)
      (q24;q11) translocation and clonal rearrangement of the immunoglobulin heavy
      chain gene. HCV-RNA, Epstein-Barr virus and Kaposi's sarcoma-associated
      herpesvirus were not identified within lymphoma cells. The finding of HCV-RNA in
      the ascitic fluid suggests a link between HCV and development of lymphoma with
      HCV playing the role of persistent antigenic stimulation to intraperitoneal B
      cell clonal expansion(s).

PMID- 9013841
TI  - A B-cell "chameleon": striking clinical, morphological, and immunophenotypic
      diversity of a single low-grade B cell clone.
AB  - A patient with an 18-year history of low-grade B-cell lymphoproliferative
      disorders is presented. Although the precise classification of these B-cell
      disorders was problematic, the blood, bone marrow, spleen, lymph node, and
      gastrointestinal lesions evaluated were compatible morphologically with such
      apparently disparate diagnoses as hairy cell leukemia, marginal zone lymphoma,
      mantle cell lymphoma, and gastrointestinal multiple lymphomatous polyposis.
      Although each low-grade disease that developed over an 18-year interval was
      clinically, morphologically, and immunophenotypically distinct, genotyping showed
      their derivation from a single B cell clone. This case emphasizes that a single B
      cell clone may give rise to several distinct low-grade B-cell lymphoproliferative
      disorders with diverse clinical and pathological features.

PMID- 9013842
TI  - Molecular follow-up of a preinvasive bronchial lesion treated by 13-cis-retinoic
      acid.
AB  - We report the result of the follow-up molecular analysis of a bronchial carcinoma
      in situ treated by 13-cis-retinoic acid, which relapsed 9 months after cessation
      of drug therapy. Loss of heterozygosity at 3p21 and 9p22 genomic sequences were
      assessed by polymerase chain reaction (PCR) after microdissection of the
      dysplastic epithelia. Despite a transient regression of the lesion to a lower
      grade with treatment, molecular analysis showed the persistence of a 3p and 9p
      deletion in all the bronchial biopsies taken in the same area during a 1 year
      follow-up, preceding by 9 months the recurrence of the carcinoma in situ. Our
      findings suggest that molecular follow-up analysis can help to assess the
      persistence of a malignant clone within a bronchial epithelium that displays a
      more benign phenotype under retinoid treatment on follow-up. Molecular analysis
      may be of great importance to evaluate the effects of chemoprevention and to
      determine the duration of such intervention in responder patients.

PMID- 9013843
TI  - Focal myositis: a polymerase chain reaction analysis for a viral etiology.
AB  - Focal myositis (FM) is a benign inflammatory condition that may clinically
      simulate a soft tissue sarcoma. It was first described in 1977, and only
      approximately 30 cases have been reported to date, yet this entity is probably
      more frequent. The pathogenesis of FM is totally unknown. It has been proposed
      that it represents a nodular form of myositis, which can evolve into
      polymyositis, but this hypothesis has not been confirmed by follow-up studies. We
      describe seven cases of FM, five of which have never been reported before.
      Histology of the lesions was very similar, showing a destructive inflammatory
      myopathy with evidence of regeneration. Our study attempted to better understand
      the pathogenesis of this focal inflammatory myopathy. We performed a polymerase
      chain reaction study to explore the presence of a number of viral infectious
      agents in the inflammed tissue. The present study failed to show the presence of
      a known viral agent with a recognized tropism for myofibers. With a panel of
      lymphoid cell markers, we also characterized the phenotype of the inflammatory
      infiltrate that was composed of many T-lymphocytes with few CD4+ cells. Lastly,
      we reviewed the published cases and discuss the possible pathogenesis.

PMID- 9013844
TI  - Morphological spectrum of follicle center cell lymphomas associated with
      infiltration of epithelioid histiocytes.

PMID- 9013845
TI  - Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC)
      transporters.
AB  - A group of ATP-binding cassette (ABC) transporters, including the yeast cadmium
      transporter (YCF1), the mammalian multidrug resistance-associated protein (MRP),
      the multispecific organic anion transporter and its congener (MOAT and EBCR), as
      well as the sulfonylurea receptor (SUR), group into a subfamily by sequence
      comparison. We suggest that these MRP-related proteins are also characterized by
      a special, common membrane topology pattern. The most studied ABC transporters,
      the cystic fibrosis transmembrane conductance regulator (CFTR) and the multidrug
      resistance (MDR) proteins, were shown to contain a tandem repeat of six
      transmembrane helices, each set followed by an ATP-binding domain. According to
      the present study, in contrast to various membrane topology predictions proposed
      for the different MRP-related proteins, they all seem to have a CFTR/MDR-like
      core structure, and an additional, large, N-terminal hydrophobic region. This
      latter domain is predicted to contain 4-6 (most probably 5) transmembrane
      helices, and is occasionally glycosylated on the cell surface. Since all the MRP
      related transporters were shown to interact with anionic compounds, the N
      terminal membrane-bound domain may have a key role in these interactions.

PMID- 9013846
TI  - Does selective gene activation direct evolution?
AB  - Mechanisms may have evolved such that the unique metabolic reaction to a
      particular environmental stress results in higher mutation rates of those genes
      most likely to solve the problem. Evidence is presented indicating that the
      environment in effect directs the evolution of organisms by (1) presenting
      various kinds of stress resulting in metabolic activities that target particular
      genes for increased rates of transcription and mutation, and (2) selecting among
      this specifically enriched mutant population those variants that alleviate the
      imposed stress. This process should be ongoing and would be expected to
      accelerate the rate of microbial evolution.

PMID- 9013847
TI  - Is leptin an insulin counter-regulatory hormone?
AB  - Leptin, the product of the ob gene, controls appetite through the hypothalamus
      and may affect many other tissues because of the widespread distribution of its
      receptors. Leptin is synthesized by white adipose tissue (WAT) under conditions
      of high energy availability and insulin stimulus. Glucocorticoids enhance this
      synthesis and catecholamines hamper leptin production. Leptin diminishes insulin
      secretion by the pancreatic beta cells and induces insulin resistance. In fact
      leptin hampers insulin action on WAT itself in a negative feedback loop. The
      evidence acquired in studies on diabetics, starvation, refeeding and insulin and
      glucose clamps supports this interpretation, which may also explain part of the
      difficulties encountered by the current postulate that links leptin to WAT mass
      size signalling to the brain. Leptin may be, essentially, a counter-regulatory
      hormone limiting the insulin drive to store energy in the form of fat, its
      effects reaching from a decrease in food intake to lower insulin secretion and
      increased resistance to insulin and lower glucose uptake and fat synthesis by
      WAT.

PMID- 9013848
TI  - Phosphorylation-independent inhibition by intracellular cyclic nucleotides of
      brain inwardly rectifying K+ current expressed in Xenopus oocytes.
AB  - An inwardly rectifying K+ current, which was heterologously expressed in Xenopus
      oocytes, was inhibited by isoproterenol, a fadrenergic agonist. Poly(A)+ mRNA
      isolated from guinea-pig brain was injected into oocytes 2-3 days before
      experiments. Isoproterenol inhibition of the K+ current was time-and voltage
      dependent: the inhibition became faster and more pronounced as the command
      voltage steps were applied to more negative potentials. This inhibition was
      prevented by propranolol. Dibutylyl cyclic (dB-c) AMP could mimic the effect of
      isoproterenol, while injection of the catalytic subunit of cAMP-dependent protein
      kinase into the oocytes did not affect the K+ current. Inhibitors of the protein
      kinases, WIPTIDE and H-8, did not prevent the inhibition by dB-cAMP. Furthermore,
      dB-cGMP also inhibited the K+ current in a similar time- and voltage-dependent
      manner. We propose that the phosphorylation-independent action of cyclic
      nucleotides mediates beta-adrenergic inhibition of brain inwardly rectifying K+
      channels expressed in Xenopus oocytes.

PMID- 9013849
TI  - Amino acid sequence of a new type of antifreeze protein, from the longhorn
      sculpin Myoxocephalus octodecimspinosis.
AB  - A new type of fish antifreeze protein, designated here type IV, has been isolated
      from the longhorn sculpin, Myoxocephalus octodecimspinosis. Sequence analysis of
      the protein (LS-12) reveals that it contains 108 amino acids, is blocked at the N
      terminus by a pyroglutamyl group and has a high (17%) content of glutamine; it is
      thus completely unrelated to the earlier described types I, II and III fish
      antifreeze proteins. Circular dichroism spectra and conformational analysis based
      on the sequence data indicate that LS-12 has a high helix content and probably
      folds as a four-helix bundle. LS-12 shows sequence similarity to certain plasma
      apolipoproteins known to have helix bundle structures, suggesting the possibility
      that LS-12 may have arisen by recruitment and mutation of a plasma
      apolipoprotein.

PMID- 9013850
TI  - Expression of the cell-adhesion molecule VCAM-1 by stromal cells is necessary for
      osteoclastogenesis.
AB  - Osteoblastic cells have been shown to be involved in osteoclast formation through
      cell to cell contacts. This study was designed to examine the possible function
      of vascular cell adhesion molecule 1 (VCAM-1) during osteoclastogenesis. As a
      source for stromal cells we used the recently established mouse bone marrow
      stromal cell line mBMS-B1 which has the ability to support osteoclastogenesis
      when used in co-culture with a crude spleen cell suspension. mBMS-B1 cells
      express a single approximately 3.9 kb VCAM-1 mRNA species. Expression was low
      under basal culture conditions and a 5-10-fold increase was observed in the
      presence of 1,25(OH)2D3. Cell surface expression of VCAM-1 examined by FACS
      analysis was increased about 2-fold after 1,25(OH)2D3 treatment.
      Immunoprecipitation of cell surface expressed VCAM-1 or total VCAM-1 protein
      using the anti-VCAM-1 monoclonal antibody MK2.7 resulted in a single
      approximately 110 kDa protein on SDS-PAGE. Induction by 1,25(OH)2D3 was about 2-5
      fold on day 3. The stromal cell-osteoclast precursor cell interaction was
      investigated in a co-culture of the mBMS-B1 and mouse spleen cells in the
      presence of 1,25(OH)2D3. The monoclonal antibody MK2.7 which is known to block
      hemopoietic-stromal cell recognition inhibited the formation of osteoclasts when
      added to the co-culture at day 2 but not day 4. These data suggest that VCAM-1 is
      involved in the interaction between stromal cells and osteoclastic precursor
      cells during osteoclastogenesis presumably most important during early stages of
      the formation of osteoclasts.

PMID- 9013851
TI  - Probing subtle acid-induced conformational changes of ribonuclease A by
      electrospray mass spectrometry.
AB  - The newly developed technique, electrospray mass spectrometry, was used to probe
      subtle conformational changes of bovine pancreatic RNase A during acid
      denaturation. In a dilute acid solution of pH 2.6, RNase A lost nearly all of its
      activity, whereas its intrinsic fluorescence intensity at 304 nm and its
      ellipticity at 222 nm were fairly resistant to denaturation by acetic acid. The
      observed maximum charged state of the enzyme in electrospray mass spectra was
      increased from 11+ (at pH 3.3) to 14+ (at pH 2.6). This could result from
      exposure of the buried basic amino acid residues R-10, K-41, H-12 and perhaps H
      48.

PMID- 9013852
TI  - The structure, function and distribution of the mouse TWIK-1 K+ channel.
AB  - The two P domain K+ channel mTWIK-1 has been cloned from mouse brain. In Xenopus
      oocytes, mTWIK-1 currents are K+-selective, instantaneous, and weakly inward
      rectifying. These currents are blocked by Ba2+ and quinine, decreased by protein
      kinase C and increased by internal acidification. The apparent molecular weight
      of mTWIK-1 in brain is 81 kDa. A 40 kDa form is revealed after treatment with a
      reducing agent, strongly suggesting that native mTWIK-1 subunits dimerize via a
      disulfide bridge. TWIK-1 mRNA is expressed abundantly in brain and at lower
      levels in lung, kidney, and skeletal muscle. In situ hybridization shows that
      mTWIK-1 expression is restricted to a few brain regions, with the highest levels
      in cerebellar granule cells, brainstem, hippocampus and cerebral cortex.

PMID- 9013853
TI  - Mercuration of vanillyl-alcohol oxidase from Penicillium simplicissimum generates
      inactive dimers.
AB  - Vanillyl-alcohol oxidase (EC 1.1.3.7) from Penicillium simplicissimum was
      modified with p-mercuribenzoate. One cysteine residue reacts rapidly without loss
      of enzyme activity. Three sulfhydryl groups then react in an 'all or none
      process' involving enzyme inactivation and dissociation of the octamer into
      dimers. The inactivation reaction is slowed down in the presence of the
      competitive inhibitor isoeugenol and fully reversible by treatment of the
      modified enzyme with dithiothreitol. Vanillyl-alcohol oxidase is more rapidly
      inactivated at low enzyme concentrations and protected from mercuration by
      antichaotropic salts. It is proposed that subunit dissociation accounts for the
      observed sensitivity of vanillyl-alcohol oxidase crystals towards mercury
      compounds.

PMID- 9013854
TI  - The interleukin 1beta-converting enzyme inhibitor CrmA prevents Apo1/Fas- but not
      glucocorticoid-induced poly(ADP-ribose) polymerase cleavage and apoptosis in
      lymphoblastic leukemia cells.
AB  - Glucocorticoids (GC) induce programmed cell death (apoptosis) in immature
      lymphocytes and are an essential component in the therapy of acute lymphatic
      leukemia. The mechanism underlying GC-induced apoptosis particularly in leukemia
      cells is, however, not well understood. Most forms of apoptosis seem to employ a
      common final effector pathway characterized by specific proteolytic events
      mediated by interleukin 1beta-converting enzyme (ICE) and/or other ICE-like
      cysteine proteases. These events may result in the morphologic changes
      characteristic of apoptosis. To determine whether a similar proteolytic pathway
      is activated during GC-induced leukemia cell apoptosis, we investigated poly(ADP
      ribose) polymerase (PARP), a typical target of ICE-like proteases, during GC
      induced apoptosis of the human acute T-cell leukemic cell line CEM-C7H2. Our
      studies showed proteolytic PARP cleavage suggestive of activation of ICE-like
      proteases that preceeded morphologic signs of apoptosis. We further established
      stably transfected CEM-C7H2 sublines expressing the cowpox virus protein CrmA
      that inhibits some, but not all, ICE-like proteases. GC-induced PARP cleavage and
      apoptosis were neither inhibited nor delayed in crmA-expressing cell lines. In
      contrast, crmA expression rendered the same lines resistant to Apo1/Fas-induced
      PARP cleavage and apoptosis. Thus, different proteases might be activated during
      the effector phases of GC-and Apo1/Fas-induced apoptosis in human leukemia cells.

PMID- 9013855
TI  - The effects of spermine and spermidine on the structure of photosystem II
      proteins in relation to inhibition of electron transport.
AB  - Polyamines (PAs) are ubiquitous in cells of higher plants and play an important
      role in many biological functions. Because PAs affect photosynthetic oxygen
      evolution, this study is designed to investigate the interaction of spermine
      (Spm) and spermidine (Spd) cations with proteins of photosystem II (PSII) using
      PSII-enriched submembranes fraction with polyamine concentrations of 0.01-10 mM.
      Fourier transform infrared (FTIR) difference spectroscopy with its self
      deconvolution and second derivative resolution enhancement as well as curve
      fitting procedures was applied, in order to determine the cation binding mode,
      the protein conformational changes and the structural properties of cation
      protein complexes. It is shown that at low polyamine concentration, cation
      protein interaction (H-bonding) is through the polypeptide C=O groups with no
      major perturbation of the protein secondary structure. As cation concentration
      increases, the polyamine complexation causes significant alterations of the
      protein secondary structure with a decrease of the alpha-helical domains from 47%
      (uncomplexed PSII) up to 37% (cation complexes) and an increase in the beta-sheet
      structure from 18% (uncomplexed PSII) up to 29% (cation complexes). Correlations
      between the effects of polyamines on protein secondary structure and on the rate
      of oxygen evolution in PSII are also established.

PMID- 9013856
TI  - Genomic organization of the KTX2 gene, encoding a 'short' scorpion toxin active
      on K+ channels.
AB  - A single intron of 87 bp, close to the region encoding the C-terminal part of the
      signal peptide, was found in the gene of the 'short' scorpion toxin kaliotoxin 2
      of Androctonus australis acting on various types of K+ channels. Its A+T content
      was particularly high (up to 86%). By walking and ligation-mediated PCR, the
      promoter sequences of the kaliotoxin 2 gene of Androctonus australis were
      studied. The transcription unit of the gene is 390 bp long. Consensus sequences
      were identified. The genes of 'short' scorpion toxins active on K+ channels are
      organized similarly to those of the 'long' scorpion toxins active on Na+ channels
      and not like those of structurally related insect defensins, which are
      intronless.

PMID- 9013857
TI  - Expression and activity of a recombinant chimeric protein composed of pokeweed
      antiviral protein and of human interleukin-2.
AB  - The pokeweed antiviral protein (PAP) has already been used to chemically
      construct immunotoxins. Here we tested the recombinant approach for the
      production of PAP-containing cytotoxic fusion-proteins. A cDNA encoding a mutated
      PAP (PAP9), which is expressed at high levels in bacteria, was fused to human
      interleukin-2 (IL-2) cDNA. The resulting PAP9-IL-2 protein was as active as the
      free PAP9 in inhibiting an eukaryotic cell-free translation system. Only the
      chimeric protein desaminated the 28S rRNA and inhibited translation of the CTLL-2
      cell line which expresses the IL-2 receptor. These results show that PAP is a
      suitable toxin for the production of recombinant immunotoxins.

PMID- 9013858
TI  - Tissue-specific subunit of the mouse cytosolic chaperonin-containing TCP-1.
AB  - We have cloned a novel Tcp-1-related mouse testis cDNA encoding a polypeptide of
      531 amino acids which shares 81.2% identity with the zeta subunit of the mouse
      cytosolic chaperonin-containing TCP-1 (CCT). Immunoblot analysis of mouse testis
      CCT subunits separated by 2-dimensional gel electrophoresis indicates that this
      novel gene, Cctz-2, encodes a CCT subunit of Mr 57 000 and pI 7.1. Cctz-2 mRNA is
      detected only in testis whereas the other Cctz gene, Cctz-1, is expressed in all
      tissues investigated. The CCTzeta-2 subunit may have specific functions in the
      folding of testicular proteins and for interactions with testicular molecular
      chaperones.

PMID- 9013859
TI  - Identification of two new mu-adaptin-related proteins, mu-ARP1 and mu-ARP2.
AB  - We report the cDNA cloning, primary structure and tissue distribution of two new
      proteins homologous to mu-adaptins, the medium chains of the clathrin coat
      adaptor complexes. Both predicted proteins share 60% amino acid sequence identity
      with each other and 27-31%, identity with mu1-adaptin (ap47) and mu2-adaptin
      (ap50). Lower similarity (23-25% identity) is found with two other mu-adaptin
      related proteins, p47A/B, and there is similarity over the N-terminal 150 amino
      acids with the adaptin small chains and deltaCOP. The mRNAs of both molecules are
      expressed in all tissues analyzed, but with different profiles of relative
      abundance. mu-ARP1 is most abundant in brain, ovary and lung, whereas mu-ARP2 is
      prominently expressed in testis. These proteins suggest the existence of as yet
      uncharacterized types of clathrin- or non-clathrin-associated protein coats in
      cellular membrane traffic, of which they are probably prototype subunits, and
      provide molecular markers and probes for their characterization.

PMID- 9013860
TI  - Cloning of the fabF gene in an expression vector and in vitro characterization of
      recombinant fabF and fabB encoded enzymes from Escherichia coli.
AB  - Analysis of the beta-ketoacyl-ACP synthase (KAS) encoded by the fabF gene of
      Escherichia coli has been hampered by a reported instability of the cloned gene.
      Here we describe biochemical characterization of purified, active protein from
      the recombinant fabF gene. This enzyme has the properties ascribed to KAS II and
      not those of a putative KAS IV reported to be encoded by fabJ, a genomic clone
      with DNA sequence identical to that of fabF. We also characterize active protein
      from a recombinant fabB gene and suggest that this method may have a general
      utility for analysis of KAS enzymes.

PMID- 9013861
TI  - Adsorption to silica nanoparticles of human carbonic anhydrase II and truncated
      forms induce a molten-globule-like structure.
AB  - Human carbonic anhydrase II pseudo-wild type (HCAIIpwt) and two truncated
      variants were adsorbed to approximately 9 nm silica nanoparticles. Ellipsometry
      was used as an indirect measure of protein adsorption. The structural changes of
      adsorbed proteins were investigated with the use of circular dichroism (CD),
      intrinsic fluorescence, ANS binding ability and inhibitor binding capacity. It
      was found that the variants that were truncated at positions 5 and 17 in the N
      terminal end attain a molten-globule-like state after interaction with the silica
      nanoparticles. In contrast, the more stable HCAIIpwt retained most of its native
      structure after 24 h adsorption to silica nanoparticles. The result suggests that
      surface induced unfolding may give rise to intermediates similar to those for
      unfolding induced by, for example GuHCl. Thus, the intermediate observed has some
      features of the molten globule.

PMID- 9013862
TI  - GAK: a cyclin G associated kinase contains a tensin/auxilin-like domain.
AB  - We have cloned a cDNA encoding a novel association partner of cyclin G by West
      Western blotting. The cDNA encodes a protein that harbors a Ser/Thr protein
      kinase-like catalytic domain at the N-terminal. Hence, we named it GAK (cyclin G
      associated kinase). The long C-terminal extension shares homology with tensin and
      auxilin, and contains a leucine zipper region. Co-immunoprecipitation and Western
      blotting showed that GAK and cyclin G associate together in vivo. GAK also co
      precipitated with CDK5, and CDK5 was found to be associated with cyclin G. We
      also showed by BIAcore analysis that the GAK-cyclin G interaction was direct.

PMID- 9013863
TI  - The cloning and characterization of human MyD88: a member of an IL-1 receptor
      related family.
AB  - Murine MyD88, an RNA with homology both to the interleukin-1 receptor signaling
      domain and to 'death-domains', is rapidly upregulated during differentiation of
      the myeloleukemic cell line M1. We have cloned the human homologue of murine
      MyD88 and re-evaluated the murine sequence. The open reading frame for both
      species encodes a 296 amino acid protein, which for murine MyD88 is 53 amino
      acids longer than originally published. Human MyD88 cDNA is encoded by 5 exons,
      and maps to chromosome 3p21.3-p22 by fluorescence in situ hybridization (FISH).
      Overexpression of the death domain region leads to transcriptional activation of
      the IL-8 promoter.

PMID- 9013864
TI  - Sesquiterpene lactone containing Mexican Indian medicinal plants and pure
      sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB.
AB  - The potential inhibitory effect of 54 Mexican Indian medicinal plants on the
      activation of transcription factor NF-kappaB was studied. Band-shift experiments
      identified the ethanolic leaf extracts of Artemisia ludoviciana ssp. mexicana,
      Calea zacatechichi, and Polymnia maculata (all rich in sesquiterpene lactones) as
      inhibitors of NF-kappaB down to a concentration of 25 microg/ml. The
      sesquiterpene lactones isohelenin and parthenolide prevented NF-kappaB activation
      completely as low as 5 microM. Treatment of HeLa cells with leaf extract of A.
      ludoviciana ssp. mexicana, isohelenin and parthenolide prevented the induction of
      transcription on the IL-6 promoter. These experiments identify the eudesmanolide
      and germacranolide type of sesquiterpene lactones as potent non-antioxidant
      inhibitors of NF-kappaB. All plants active in the NF-kappaB assay also showed a
      delay in the onset of capillary reactions of the allantois membrane in a
      physiological model for anti-inflammatory activity - the HET-CAM assay.

PMID- 9013865
TI  - The role of structural domains in RIP II toxin model membrane binding.
AB  - The interaction of plant toxin ricin and MLI binding subunits to liposomes
      containing monosialoganglioside (GM1), bearing a terminal galactose residue, has
      been examined as a possible receptor model. For the first time we demonstrate
      that ricin B-chain but not ricin provokes liposome aggregation at 10 M% GM1
      concentration, whereas in the presence of either ricin A-chain or galactose the
      aggregation is inhibited. The B-subunit of plant toxin MLI from Viscum album has
      similar lectin specificity and activity but cannot aggregate GM1 liposomes. The
      ability of the B-chain to aggregate liposomes adds a new crucial step in the
      toxin transmembrane penetration mechanism. We demonstrate here possible ricin B
      chain interactions with membranes proceeding via two sites, namely (a) a
      galactose-binding domain and (b) a hydrophobic interchain domain. In close
      contact with two phospholipid bilayers, ricin B-chain may determine the geometry
      of the fusion site. These events can provoke A-chain translocation which follows
      membrane fusion.

PMID- 9013866
TI  - Genetically engineered mice as animal models for NIDDM.
AB  - Genetically engineered animals carrying defined alterations in their genome can
      represent invaluable tools for better understanding complex polygenic diseases
      such as non-insulin-dependent diabetes mellitus (NIDDM) at the molecular level.
      The structure or expression of a number of genes potentially involved in insulin
      action or pancreatic beta-cell function have recently been altered in the mouse
      using transgenic or gene-targeting approaches. The obtention of such mice is the
      first step towards the development of animal models carrying multiple gene
      defects which would be very useful in NIDDM research.

PMID- 9013867
TI  - Reduction of protein disulfide bonds in an oxidizing environment. The disulfide
      bridge of cholera toxin A-subunit is reduced in the endoplasmic reticulum.
AB  - Following retrograde transport to the endoplasmic reticulum (ER) the A-subunit of
      cholera toxin (CTX-A) is partially cleaved into CTX-A1 and CTX-A2 by reduction of
      a disulfide bridge [Majoul et al. (1996) J. Cell Biol. 133, 777-789], although
      the redox state in the ER favors disulfide formation. We show here that the
      disulfide bridge of CTX-A is cleaved in vitro already at GSH/GSSG ratios between
      1 and 3. Protein disulfide isomerase (PDI) exerts only a minor accelerating
      effect. Various mixed disulfide intermediates (CTX-A1-S-S-CTX-A1; PDI-S-S-A2; PDI
      S-S-A1) appear during CTX-A reduction. These results indicate that in the ER
      protein disulfide formation and protein disulfide reduction can take place
      simultaneously.

PMID- 9013868
TI  - Isolation and characterization of a cDNA encoding a Translin-like protein, TRAX.
AB  - Translin is a DNA binding protein which specifically binds to consensus sequences
      at breakpoint junctions of chromosomal translocations in many cases of lymphoid
      malignancies. To investigate its functional significance at such recombination
      hotspots, we examined whether Translin interacts with other proteins using a
      yeast two-hybrid system and identified an associated 33 kd protein partner, TRAX,
      with extensive amino acid homology. The TRAX protein was established to contain
      bipartite nuclear targeting sequences in its N-terminal region, suggesting a
      possible role in the selective nuclear transport of Translin protein lacking any
      nuclear targeting motifs.

PMID- 9013869
TI  - Solubility diagram of the Rhodobacter sphaeroides reaction center as a function
      of PEG concentration.
AB  - In order to quantify the effect of polyethylene glycol 4000 (PEG) on the
      solubility of an integral membrane protein, we have crystallized the
      photochemical reaction center from Rhodobacter sphaeroides Y by batch method on a
      large range of PEG. The measurement of the solubility diagram display a semi
      logarithmic dependence of solubility versus PEG concentration. Comparison of our
      results with previously published ones [Odahara, T., Ataka, M. and Katsura, M.
      (1994) Acta Cryst. D50, 639-642] suggests a notable effect of additional 1,2,3
      heptane-triol and/or temperature on photochemical reaction center solubility.

PMID- 9013870
TI  - Rat prolactin synthesis by lactating mammary epithelial cells.
AB  - It has previously been suggested that the mammary cell could produce prolactin
      (PRL). This hypothesis was investigated by incubation with [35S]methionine
      cysteine followed by SDS-PAGE, immunoblotting and autoradiography of
      immunoprecipitated PRL, and by electron microscopic analysis after incubation
      without or with cycloheximide. Immunoreactive 14-, 23-, 25-, 32- and 36-kDa PRL
      forms were radioactive. By two-dimensional electrophoresis analysis,
      immunoreactive and radioactive spots, of about 25 kDa and high molecular weight,
      were also detected. After incubation of mammary epithelial cells with
      cycloheximide, immunogold electron microscopy showed a drastic decrease of
      labelling in organelles involved in synthesis and secretion, compared to those
      incubated in control medium. These results make it possible to conclude that
      lactating mammary tissue is able to synthesize PRL.

PMID- 9013871
TI  - Oxidation of N(G)-hydroxyl-L-arginine to nitric oxide mediated by respiratory
      burst: an alternative pathway to NO synthesis.
AB  - N(G)-Hydroxy-L-arginine is an intermediate metabolite in the synthesis of nitric
      oxide that is upregulated and secreted during acute inflammation in vivo.
      Previous reports have shown that chemically induced superoxide anion oxidizes
      N(G)-hydroxy-L-arginine to nitric oxide. Here, we demonstrate that this reaction
      takes place physiologically in phagocytic cells during the respiratory burst, and
      is independent of the presence of nitric oxide synthase.

PMID- 9013872
TI  - NMR structural characterization of the CDK inhibitor p19INK4d.
AB  - p19INK4d is a 165 amino acid protein that belongs to the INK4 family of CDK4 and
      CDK6 inhibitors. Assignments of 1H, 15N and 13C resonances have enabled the
      determination of the secondary structure of the protein which is largely alpha
      helical (residues 14-18, 21-29, 54-62, 77-83, 87-95, 110-116, 120-128, 142-148
      and 152-160). The protein comprises five 32-amino acid ankyrin-like repeats; each
      ankyrin repeat contains a helix-beta-turn-helix core. The exception is the second
      ankyrin repeat, which lacks the first helix. All beta-turns have a central
      glycine residue flanked by two residues in beta-conformations. There is also a
      high conservation of Ala at position 8 in the first helix and Leu-Leu(Val) at
      positions 17-18 of the second helix in all ankyrin repeats of p19. The location
      of the helix-turn-helix segments found in p19 should be general for all other
      members of the INK4 family, including, for example, a homologous tumor suppressor
      p16INK4a. 1H-15N heteronuclear steady-state NOE measurements on p19 indicate that
      most of the backbone of p19INK4d exists in a well defined structure of limited
      conformational flexibility on the nano- to picosecond time scale.

PMID- 9013873
TI  - Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is
      tyrosine phosphorylated in response to interleukin-6.
AB  - Vav is a hematopoietic cell-specific proto-oncogene. We show that interleukin-6
      (IL-6) induces transient tyrosine phosphorylation of Vav in a human myeloma cell
      line, U266. A membrane-distal part of the cytoplasmic region of gp130 is critical
      for association between Vav and gp130, and the IL-6-induced tyrosine
      phosphorylation of Vav. Mitogen-activated protein kinase (MAPK) (p42MAPK or
      extracellular signal-regulated kinase 2 (Erk2)) is coprecipitated with Vav. MAPK
      activity in the anti-Vav immunoprecipitates is upregulated by IL-6 stimulation.
      Furthermore Vav is associated with Grb2 which is known as an adapter protein
      leading to Ras activation. The results imply that Vav may link gp130 activation
      to downstream MAPK activation in hematopoietic cells.

PMID- 9013874
TI  - Folding intermediates of beta-lactamase recognized by GroEL.
AB  - beta-Lactamase, from which the disulfide bond was removed by two Cys-->Ala
      mutations, forms stable complexes with GroEL only during the first 30 s of
      folding, while wild-type beta-lactamase forms no stable complex under these
      conditions. The 3-phasic kinetics of folding are very similar between wild-type
      and mutant. After 4 s, Trp-210 is already juxtaposed to the disulfide bond, but
      proline cis-trans isomerization has not yet taken place and almost no enzymatic
      activity is observed. This shows that GroEL is unable to bind late folding
      intermediates and also discriminates between the degree of unfolding possible in
      wild-type disulfide-containing beta-lactamase and the Cys-Ala mutant.

PMID- 9013875
TI  - Cysteine-153 is required for redox regulation of pea chloroplast fructose-1,6
      bisphosphatase.
AB  - Chloroplastic fructose-1,6-bisphosphatases are redox regulatory enzymes which are
      activated by the ferredoxin thioredoxin system via the reduction/isomerization of
      a critical disulfide bridge. All chloroplastic sequences contain seven cysteine
      residues, four of which are located in, or close to, an amino acid insertion
      region of approximately 17 amino acids. In order to gain more information on the
      nature of the regulatory site, five cysteine residues (Cys49, Cys153, Cys173,
      Cys178 and Cys190) have been modified individually into serine residues by site
      directed mutagenesis. While mutations C173S and C178S strongly affected the redox
      regulatory properties of the enzyme, the most striking effect was observed with
      the C153S mutant which became permanently active and redox independent. On the
      other hand, the C190S mutant retained most of the properties of the wild-type
      enzyme (except that it could now also be partially activated by the
      NADPH/NTR/thioredoxin h system). Finally, the C49S mutant is essentially
      identical to the wild-type enzyme. These results are discussed in the light of
      recent crystallographic data obtained on spinach FBPase [Villeret et al. (1995)
      Biochemistry 34, 4299-4306].

PMID- 9013876
TI  - Ceramide induces apoptosis in PC12 cells.
AB  - The novel lipid second messenger, ceramide, induced apoptosis in PC12 cells as
      determined morphologically by nuclear appearance and internucleosomal DNA
      fragmentation. Apoptosis was induced by exogenous C2-ceramide in a dose- and time
      dependent manner. Natural ceramide and C6-ceramide had a similar effect. This
      response was specific since the structural analog C2-dihydroceramide and other
      related lipids failed to initiate apoptosis. The apoptotic effect of ceramide
      also depends critically on cell plating density. Furthermore, the peptide
      inhibitor of interleukin-1beta converting enzyme (ICE)-like proteases, Z-VAD.FMK,
      completely prevented the nuclear changes induced by ceramide, implicating the
      involvement of ICE-like protease activation in ceramide-induced apoptosis in PC12
      cells.

PMID- 9013877
TI  - Very fast electron transfer from cytochrome to the bacterial photosynthetic
      reaction center at low temperature.
AB  - Electron transfer from the proximal heme c-559 to the primary donor P has been
      studied in reaction centers of the photosynthetic bacterium Rhodopseudomonas
      viridis in which the tyrosine residue L162 was replaced by threonine. In the wild
      type, when the two high-potential hemes of the tetraheme cytochrome are reduced
      before flash excitation, a rapid electron transfer (t1/2 = 190 ns) observed at
      ambient temperature disappears below 190 K. In the mutant, the reaction is partly
      maintained down to 8 K, leading to irreversible charge separation. The reaction
      rate is nearly temperature-independent between 294 K and 8 K (t1/2 approximately
      450 ns). The different behavior of wild type and mutant reaction centers is
      attributed to differences in a network of water molecules, the freezing of which
      may block structural reorganizations associated with cytochrome oxidation, in the
      wild type but not in the mutant.

PMID- 9013878
TI  - Sub-mitochondrial localization of the catalytic subunit of pyruvate dehydrogenase
      phosphatase.
AB  - Using a specific antibody against the PDP catalytic subunit, PDPc, precise
      localization of this subunit in mitochondria was performed. Sub-fractionation of
      purified mitochondria by controlled swelling processes led to the isolation of
      outer membranes, matrix space and inner membrane vesicles which were purified on
      a sucrose density gradient. In this study, we demonstrated that PDPc was not
      recovered as a soluble protein in the matrix space but was associated with the
      inner membrane. Moreover, Triton X-114 phase partitioning performed on inner
      membranes showed that PDPc behaved both as a hydrophilic and as a hydrophobic
      protein, thus suggesting two different forms of this enzyme.

PMID- 9013879
TI  - Cloning of the human IL-13R alpha1 chain and reconstitution with the IL4R alpha
      of a functional IL-4/IL-13 receptor complex.
AB  - The human homologue of the recently cloned murine IL-13 binding protein (IL-13R
      alpha1) was cloned from a cDNA library derived from the carcinoma cell line CAKI
      1. The cloned cDNA encodes a 427 amino acid protein with two consensus patterns
      characteristic of the hematopoietic cytokine receptor family and a short
      cytoplasmic tail. The human protein is 74% identical to the murine IL-13R alpha1,
      and 27% identical to the human IL-13R alpha2. CHO cells expressing recombinant
      hIL-13R alpha1 specifically bind IL-13 (Kd approximately 4 nM) but not IL-4. Co
      expression of the cloned cDNA with that of IL-4R alpha resulted in a receptor
      complex that displayed high affinity for IL-13 (Kd approximately 30 pM), and that
      allowed cross-competition of IL-13 and IL-4. Electrophoretic mobility shift assay
      showed that IL-13 and IL-4 were able to activate Stat6 in cells expressing both
      IL-4R alpha and IL-13R alpha1, while no activation was observed in cells
      expressing either one or the other alone.

PMID- 9013880
TI  - Ozone depletes tocopherols and tocotrienols topically applied to murine skin.
AB  - To evaluate ozone damage to hairless mouse skin, two parameters of oxidative
      damage, vitamin E depletion and malondialdehyde (MDA) production, were measured
      in vitamin E-enriched and in control skin from mice exposed to ozone (10 ppm). A
      5% vitamin E solution (tocotrienol-rich fraction, TRF) in polyethylene glycol
      (PEG) was applied to 2 sites on the back of hairless mice, PEG to 2 sites. After
      2 h, the sites were washed, one of each pair of sites covered and the mice
      exposed ozone for 2 h. Ozone exposure (compared with covered sites) increased
      epidermal MDA in PEG-treated sites, while vitamin E was unchanged. In contrast,
      ozone exposure significantly depleted vitamin E in TRF-treated sites, while
      significant MDA accumulation was prevented. This is the first demonstration that
      ozone exposure causes damage to cutaneous lipids, an effect which can be
      attenuated by vitamin E application.

PMID- 9013881
TI  - Identification of a conserved phosphorylation site modulating nuclear lamin
      polymerization.
AB  - Mitotic lamin disassembly results from phosphorylation at specific sites. In
      vitro, lamins can form head-to-tail polymers that disassemble upon
      phosphorylation by cdc2 kinase. A co-immunoprecipitation assay, employing
      Drosophila nuclear lamin Dm0 fragments was used to study the effect of
      phosphorylation on head-to-tail binding. Phosphorylation of serine-50 by cAMP
      dependent kinase inhibited head-to-tail binding in the same manner as
      phosphorylation of serine-42 by cdc2 kinase. Results suggest that multiple
      pathways may be employed to disassemble nuclear lamins in vivo.

PMID- 9013882
TI  - Acetylation of ribosomal protein S5 affected by defects in the central pseudoknot
      in 16S ribosomal RNA?
AB  - We have analyzed the ribosomal protein profile of Escherichia coli 30S subunits
      with the mutation C18A in the central pseudoknot of their 16S ribosomal RNA. This
      mutation was shown to inhibit translational activity in vivo and to affect
      ribosome stability in vitro. The majority of the mutant 30S particles were
      present as free subunits in which a reproducible decrease in amount of proteins
      S1, S2, S18 and S21 was observed. The protein gels also showed the appearance of
      a satellite band next to S5. This band reacted with anti-S5 antibodies and had a
      slightly increased positive charge. The simplest interpretation of these
      findings, also considering published data, is that the satellite band is S5 with
      a non-acetylated N-terminal alanine. Underacetylation of S5 due to mutations in
      the 16S rRNA implies that the modification is performed on the ribosome.

PMID- 9013883
TI  - The adeno-associated virus Rep78 major regulatory protein forms multimeric
      complexes and the domain for this activity is contained within the carboxy-half
      of the molecule.
AB  - The adeno-associated virus (AAV) encoded Rep78 is a multifunctional protein which
      is able to regulate transcription, is required for AAV DNA replication, and
      appears necessary for site specific integration of AAV DNA into human chromosome
      19. Being analogous to the large T antigen, the replication protein of
      polyomaviruses which is known to homo-multimerize, it seemed likely that the
      Rep78 protein would also interact with itself to carry out at least some of its
      functions. Furthermore, in electrophoretic mobility shift assay studies by many
      laboratories on Rep78/68 protein interaction with AAV terminal repeat DNA it has
      been noticed that multiple high bands often result. These data suggest Rep78
      Rep78 interaction. In this study it is directly demonstrated that Rep78 is able
      to form multimeric complexes as measured by West-Western and chemical cross
      linking assays. Furthermore, using an amino-truncated Rep78 protein, it is
      demonstrated that the Rep78 homo-multimerization domain is contained within the
      carboxy-half of the protein.

PMID- 9013884
TI  - The C-terminal domain of the Gs-coupled EP4 receptor confers agonist-dependent
      coupling control to Gi but no coupling to Gs in a receptor hybrid with the Gi
      coupled EP3 receptor.
AB  - Prostaglandin E2 receptors (EPR) belong to the family of G-protein-coupled
      receptors with 7 transmembrane domains. They form a family of four subtypes,
      which are linked to different G-proteins. EP1R are coupled to Gq, EP2 and EP4R to
      Gs and EP3R to Gi. Different C-terminal splice variants of the bovine EP3R are
      coupled to different G-proteins. A mouse EP3R whose C-terminal domain had been
      partially truncated no longer showed agonist-induced Gi-protein activation and
      was constitutively active. In order to test the hypothesis that the C-terminal
      domain confers coupling specificity of the receptors on the respective G
      proteins, a cDNA for a hybrid rEP3hEP4R, containing the N-terminal main portion
      of the Gi-coupled rat EP(3beta)R including the 7th transmembrane domain and the
      intracellular C-terminal domain of the Gs-coupled human EP4R, was generated by
      PCR. HEK293 cells transiently transfected with the chimeric rEP3hEP4R cDNA
      expressed a plasma membrane PGE2 binding site with a slightly lower Kd value for
      PGE2 but an identical binding profile for receptor-specific ligands as cells
      transfected with the native rat EP(3beta)R. In HepG2 cells stably transfected
      with the chimeric rEP3hEP4R cDNA PGE2 did not increase cAMP formation
      characteristic of Gs coupling but attenuated the forskolin-stimulated cAMP
      synthesis characteristic of Gi coupling. This effect was inhibited by pre
      treatment of the cells with pertussis toxin. Thus, the hybrid receptor behaved
      both in binding and in functional coupling characteristics as the native rat
      EP(3beta)R. Apparently, the intracellular C-terminal domain did not confer
      coupling specificity but coupling control, i.e. allowed a signalling state of the
      receptor only with agonist binding.

PMID- 9013885
TI  - Phosphatidylinositol 4,5-bisphosphate specifically stimulates PP60(c-src)
      catalyzed phosphorylation of gelsolin and related actin-binding proteins.
AB  - Gelsolin is a widely distributed Ca2+-dependent regulator of the cortical actin
      network. We demonstrate that gelsolin is phosphorylated by pp60(c-src) and that
      this phosphorylation is dramatically enhanced by phosphatidylinositol 4,5
      bisphosphate (PIP2), known to specifically interact with gelsolin. Other
      phospholipids display only a marginal effect. pp56(lck), a tyrosine kinase of the
      same family, does not phosphorylate gelsolin. Other mammalian actin-binding
      proteins such as profilin and CapG but also fragmin from Physarum polycephalum
      are similar targets for PIP2-stimulated pp60(c-src) phosphorylation.

PMID- 9013886
TI  - Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex
      NCp7:vpr.
AB  - The effects of HIV-1 encoded proteins NCp7, vpr and NCp7:vpr complex on the
      activity of protein phosphatase-2A0 have been tested. We report that NCp7 is an
      activator of protein phosphatase-2A0 and that vpr activated protein phosphatase
      2A0 only slightly. We also report that NCp7 and vpr form a tight complex which
      becomes a more potent activator of protein phosphatase-2A0 than NCp7 alone. The
      ability of NCp7 to activate protein phosphatase-2A0 is regulated by vpr. The C
      terminal portion of vpr prevents NCp7 from activating protein phosphatase-2A0
      while the N-terminal portion of vpr potentiates the effect of NCp7 on the
      activity of protein phosphatase-2A0. Our findings indicate that vpr may be acting
      as a targeting subunit which directs NCp7 to activate protein phosphatase-2A0. In
      view of the fact that protein phosphatase-2A functions as an inhibitor of G0 to M
      transition of the cell cycle and is involved in other key cellular processes such
      as the control of RNA transcription, the results presented in this report may
      explain how HIV-1 causes cell cycle arrest which may lead to CD4+ T cell
      depletion and also how it disturbs normal cellular processes of its host cell.

PMID- 9013887
TI  - An increase in cytosolic calcium ion concentration precedes hypoosmotic shock
      induced activation of protein kinases in tobacco suspension culture cells.
AB  - Hypoosmotic shock induced a transient increase in cytosolic free calcium
      concentration [Ca2+]cyt and subsequent activation of 50-, 75- and 80-kDa protein
      kinases in tobacco (Nicotiana tabacum L.) suspension culture cells. Depletion of
      external calcium suppressed both the elevation of [Ca2+]cyt and the activation of
      protein kinases in response to hypoosmotic shock, indicating that the elevation
      of [Ca2+]cyt is prerequisite for the activation of protein kinases.
      Pharmacological analysis indicated that the hypoosmotic shock-activated protein
      kinases were activated by phosphorylation, suggesting that the activities of
      these protein kinases are regulated by putative protein kinases. These results
      suggest that the hypoosmotic signal is transduced to protein kinase cascades
      which are triggered by [Ca2+]cyt elevation.

PMID- 9013888
TI  - Lack of vacuolar proton ATPase association with the cytoskeleton in osteoclasts
      of osteosclerotic (oc/oc) mice.
AB  - We examined the pathogenetic mechanism underlying the lack of bone resorption in
      osteosclerotic oc/oc mice. An immunoelectron microscopic analysis revealed that
      in the osteoclasts of these mice, no ruffled borders formed, and that vacuolar H+
      ATPase (V-ATPase) was present throughout the cytoplasm but not on the apical
      membranes. The activity of V-ATPase in oc/oc mice was similar to that in normal
      mice. In normal spleen cell-derived osteoclast-like cells (OCLs),
      immunoreactivity for V-ATPase was detected in association with Triton X-100
      insoluble cellular structure, but not in oc/oc spleen cell-derived OCLs.
      Moreover, in renal proximal convoluted tubules of oc/oc mice, the basal striation
      did not form. These results suggest that osteosclerosis in oc/oc mice is possibly
      due to the dissociation of V-ATPase and cytoskeleton in osteoclasts.

PMID- 9013889
TI  - Murine tissue inhibitor of metalloproteinases-4 (Timp-4): cDNA isolation and
      expression in adult mouse tissues.
AB  - We have isolated cDNA clones corresponding to a new member of the murine tissue
      inhibitor of metalloproteinase (TIMP) family, designated Timp-4. The nucleotide
      sequence predicts a protein of 22,609 Da that contains the characteristic 12
      cysteine TIMP signature. TIMP-4 is more closely related to TIMP-2 and TIMP-3 than
      to TIMP-1 (48%, 45% and 38% identity, respectively). Analysis of Timp-4 mRNA
      expression in adult mouse tissues indicated a 1.2 kb transcript in brain, heart,
      ovary and skeletal muscle. This pattern of expression distinguishes Timp-4 from
      other Timps, suggesting that the TIMP-4 protein may be an important tissue
      specific regulator of extracellular matrix remodelling.

PMID- 9013891
TI  - Isoform-dependent activation of adenylyl cyclase by proteolysis.
AB  - Recent findings have suggested that the cellular proteolytic system plays a major
      role in the regulation of various intra- and extra-cellular signaling. It was
      previously shown that proteolytic treatment of adenylyl cyclase leads to the
      activation of this enzyme. We demonstrate that this activation occurs in an
      adenylyl cyclase isoform-dependent manner. The type II isoform was strongly
      activated (approximately 500%), the type III isoform was modestly activated
      (approximately 30%),and the type V isoform was inhibited by trypsin. Activation
      of type II adenylyl cyclase occurred in trypsin dose- and time-dependent manners
      and was blocked by a trypsin inhibitor in a dose-dependent manner. Other
      proteases, such as thrombin and plasminogen, similarly activated the type II
      isoform, but not the others. Our data suggest that proteolytic activation is an
      isoform- and thus cell type-dependent mechanism of altering adenylyl cyclase
      catalytic activity.

PMID- 9013890
TI  - Molecular cloning of a novel mouse aspartic protease-like protein that is
      expressed abundantly in the kidney.
AB  - By use of the signal sequence trap method, we isolated a cDNA encoding a novel
      aspartic protease-like protein from the mouse kidney, and termed it 'kidney
      derived aspartic protease-like protein (KAP).' The protein, a 419-amino-acid
      polypeptide with a 16-amino-acid signal sequence, had 47% identity with mouse
      cathepsin D, and its overall structure was closely related to known aspartic
      proteases. Northern blot analysis revealed that KAP mRNA is expressed at the
      highest level in the kidney, at a moderate level in the lung, and at low levels
      in the spleen and adipose tissue. In situ hybridization analysis demonstrated
      that the mRNA is expressed abundantly in the proximal straight tubule and
      slightly, but significantly, in the proximal convoluted tubule in the kidney.
      This intra-renal distribution differs distinctly from those of previously
      reported proteases such as cathepsins B, D, and H.

PMID- 9013892
TI  - Association of aminopeptidase N and endopeptidase 24.15 inhibitors potentiate
      behavioral effects mediated by nociceptin/orphanin FQ in mice.
AB  - The behavioral effects induced by central administration in mice of the
      endogenous ORL1 (opioid receptor-like1) ligand, nociceptin/orphanin FQ, were
      investigated in the absence or presence of inhibitors of aminopeptidase N
      (bestatin) and endopeptidase 24.15 (Z-(L,D)Phe psi(PO2CH2)(L,D)Ala-Arg-Phe)
      recently shown to be involved in the metabolism of the heptadecapeptide in vitro.
      A severe reduction in motor activity induced by nociceptin/orphanin FQ was
      measured in two tests (spontaneous motor activity and open field). This
      pharmacological effect was shown to be potentiated by the association of bestatin
      and Z-(L,D)Phe psi(PO2CH2)(L,D)Ala-Arg-Phe, confirming in vivo the involvement of
      these peptidases in nociceptin/orphanin FQ inactivation. In our conditions, these
      inhibitors were devoid of intrinsic effects, suggesting a low tonic regulation by
      the heptadecapeptide of the measured behaviour.

PMID- 9013893
TI  - Green tea catechins such as (-)-epicatechin and (-)-epigallocatechin accelerate
      Cu2+-induced low density lipoprotein oxidation in propagation phase.
AB  - Effects of (-)-epicatechin (EC) and (-)-epigallocatechin (EGC) on Cu2+-induced
      low density lipoprotein (LDL) oxidation were studied in initiation and
      propagation phases. When 1.5 microM EC or EGC was added to the mixture of
      isolated human LDL and Cu2+ in the initiation phase, the oxidation of LDL was
      inhibited in agreement with previous findings. In contrast, in the propagation
      phase, 1.5 microM of EC or EGC worked as an accelerator of the oxidation, and
      acceleration ratios (maximum about 6 times) were modified depending on the
      concentrations of catechin used and the oxidation process in the propagation
      phase. The evidence was obtained from formation of thiobarbituric acid reactive
      substances (TBARS), detecting conjugated diene measured by absorbance at 234 nm
      and investigating fragmentation of apoprotein B (apo B) in LDL. Even in the
      propagation phase of LDL oxidation, the elevated concentrations of EC or EGC
      worked as inhibitors: after 40 min incubation of LDL with Cu2+, 10.0 microM EC or
      2.0 microM EGC inhibited LDL oxidation. Yet, nitric oxide (NO) released from 5
      microM zwitterionic polyamine/NO adducts had an inhibitory in all phases of LDL
      oxidation. These results indicate that catechins such as EC and EGC can act as
      free radical terminators (reducing agents) or accelerators (oxidizing agents)
      under oxidation circumstances, which is a different character from NO. From the
      above evidence, further investigations are needed on many natural flavonoids, the
      most potent antioxidative compounds in foods.

PMID- 9013894
TI  - Further evidence for a common mechanism for shedding of cell surface proteins.
AB  - Pro-TNF alpha, Steel factor, type II IL-1R and IL-2R alpha were expressed in COS
      7 cells and the generation of their soluble forms was examined. The release of
      all four proteins was strongly stimulated by the phorbol ester PMA and completely
      blocked by a hydroxamate-based inhibitor of metalloproteases. COS-7 cell
      membranes were found to cleave various synthetic pro-TNF alpha peptides with the
      same specificity as a partially purified TNF alpha converting enzyme purified
      from human monocytic cells, suggesting that the same enzyme may be responsible
      for at least some of the COS-7 cell shedding activity.

PMID- 9013895
TI  - Phytoalexin production by amino acid conjugates of jasmonic acid through
      induction of naringenin-7-O-methyltransferase, a key enzyme on phytoalexin
      biosynthesis in rice (Oryza sativa L.).
AB  - Amino acid conjugates of jasmonic acid are found to elicit production of the
      flavonoid phytoalexin, sakuranetin in rice leaves. The elicitation is shown to
      arise from induction of naringenin 7-O-methyltransferase, a key enzyme of
      sakuranetin biosynthesis. The (-)-phenylalanine conjugate, one of the active
      compounds, is characterized by high activity for both sakuranetin and enzyme
      induction and low phytotoxicity against rice growth. Both (+)-enantiomers of the
      conjugates and free amino acids do not show any activity. The amino acid
      conjugate of jasmonic acid is speculated to be the later component in the
      signaling transduction chain in stressed rice plants.

PMID- 9013896
TI  - Identification of a C-terminal binding site for G-protein betagamma-subunits in
      phosducin-like protein.
AB  - Phosducin-like protein (PhLP) has recently been identified as a ubiquitous
      inhibitor of G-protein betagamma-subunit (G betagamma)-mediated signaling, with
      an affinity about 5-fold lower than that of phosducin. The G betagamma binding
      site of phosducin has been suggested to be contained in its N-terminus. A region
      corresponding to this N-terminus is lacking in PhLP, suggesting that PhLP must
      utilize a different mode of G betagamma binding. To map the G betagamma binding
      site in PhLP, a series of deletion mutants were constructed, expressed in E. coli
      as glutathione S-transferase (GST) fusion proteins, and the purified fusion
      proteins were examined for their ability to attenuate G(o) GTPase activity.
      Progressive N-terminal truncations of PhLP caused only minor reductions in
      potency, whereas the complementary N-terminal PhLP fragments turned out to be
      inactive. We further identified a short C-terminal segment comprising residues
      168 to 195 that inhibited G0 GTPase activity similar in efficacy and potency to
      full-length PhLP. This C-terminal fragment was also capable of antagonizing a
      second G betagamma-mediated function, the enhancement of rhodopsin
      phosphorylation by the beta-adrenergic receptor kinase. Taken together, these
      data indicate that PhLP interacts with G betagamma via a short C-terminal binding
      site which is distinct from that identified previously in phosducin.

PMID- 9013897
TI  - Nuclear translocation of PKC zeta during ischemia and its inhibition by
      wortmannin, an inhibitor of phosphatidylinositol 3-kinase.
AB  - Protein kinase C zeta (PKC zeta), a member of the atypical PKC subgroup, is
      insensitive to Ca2+, diacylglycerol, and phorbol esters, but is activated by
      phospholipids such as phosphatidylinositol-3,4,5-triphosphate, a product of
      phosphatidylinositol 3-kinase (PI3-kinase). Here we show that PKC zeta
      translocates from the cytosol to the 1000 x g pellet (nuclear-myofibrillar)
      fraction during ischemia for 40 min in Langendorff-perfused rat hearts. In
      addition, immunohistochemical observation shows that ischemia induces the
      translocation of PKC zeta to the nucleus. The nuclear translocation during
      ischemia is inhibited in a dose-dependent manner by wortmannin (10(-9)-10(-7) M),
      an inhibitor of PI3-kinase.

PMID- 9013898
TI  - Molecular cloning of a novel gene involved in serotonin receptor-mediated signal
      transduction in rat stomach.
AB  - In Xenopus oocytes injected with small size mRNAs (500-700 b), obtained from rat
      stomach by fractionation, application of 10 microM 5-HT induced a substantial
      Ca2+-activated Cl- current (I(Cl-Ca)). I(Cl-Ca) was not elicited by 5-HT in
      native oocytes. Consistent results from this assay in the oocyte expression
      system motivated cDNA cloning experiments. A novel cDNA (named rat stomach
      serotonin receptor-related cDNA: RSS cDNA) which encodes a small protein involved
      in specific 5-HT receptor-mediated I(Cl-Ca) activation was identified. The
      molecular weight of RSS protein in the reticulocyte lysate translation system
      (approximately 10 kDa) is identical to that calculated from the amino acid
      sequence. Computer-aided analysis of the predicted protein does not show any
      obvious sequence homologies (< 18%) to any other proteins including G protein
      coupled receptors. Northern analysis revealed that RSS mRNA is ubiquitously
      expressed at varying levels in a number of different tissues. Furthermore, the
      binding of [3H]spiperone, a 5-HT2 receptor antagonist, was examined in CHO cells,
      which highly expressed RSS transcripts (named CHO-RSS). Specific binding of
      [3H]spiperone was not clearly observed in native CHO but was detected in CHO-RSS.
      The dissociation constant was 10.3 nM in CHO-RSS. These results suggest that RSS
      protein may be a factor which facilitates 5-HT receptor expression or,
      alternatively, an enhancer of the affinity of native 5-HT receptor to 5-HT.

PMID- 9013899
TI  - A fragment of the major histocompatibility complex class II-associated p41
      invariant chain inhibits cruzipain, the major cysteine proteinase from
      Trypanosoma cruzi.
AB  - A peptide fragment derived from the p41 form of the invariant chain (Ii)
      associated with the major histocompatibility complex (MHC) class II molecule has
      been shown to inhibit the mammalian lysosomal cysteine proteinase, cathepsin L,
      and to be a novel cysteine proteinase inhibitor, distinct from cystatins. Here we
      report that this same fragment also binds to and inhibits cruzipain, the
      cathepsin L-like enzyme from the protozoan parasite Trypanosoma cruzi. The
      binding of the Ii fragment to cruzipain is fast (k(ass) = 2.4 x 10(7) M(-1) s(-1)
      and tight (Ki = 5.8 x 10(-11) M). The inhibition is competitive. These results
      suggest the possibility of using the invariant chain as a model for the specific
      inhibition of cruzipain in vivo, i.e. as a potential drug to combat Chagas'
      disease.

PMID- 9013900
TI  - The carotenoids beta-carotene, canthaxanthin and zeaxanthin inhibit macrophage
      mediated LDL oxidation.
AB  - Human monocyte-macrophages were incubated for 24 h in Ham's F-10 medium with
      human low-density lipoprotein (LDL) in the presence or absence of beta-carotene,
      canthaxanthin or zeaxanthin, at final concentrations of 2.5, 12.5 and 25 mg/l.
      LDL oxidation, measured by agarose gel electrophoresis, the thiobarbituric acid
      assay and gas chromatography, was inhibited by each of the carotenoids in a
      concentration-dependent manner. Canthaxanthin was more effective when
      incorporated into LDL before addition to the cultures whereas beta-carotene and
      zeaxanthin were more effective when added simultaneously with LDL. The results
      suggest that dietary carotenoids might help slow atherosclerosis progression.

PMID- 9013901
TI  - C/EBP alpha is a major activator for the transcription of rat Cu/Zn superoxide
      dismutase gene in liver cell.
AB  - The rat Cu/Zn superoxide dismutase (SOD1) is expressed in all tissues. Sequence
      analysis of the SOD1 promoter region showed that none of the cis-elements of
      hepatocyte-specific nuclear factors (HNF) were observed. The cis-element of C/EBP
      alpha in the proximal region of the SOD1 promoter and the high level of C/EBP
      alpha in the liver tissue led us to focus on the transcriptional regulation of
      the SOD1 gene by C/EBP alpha. Cotransfection assays with the plasmid expressing
      transcription factor C/EBP alpha showed that C/EBP alpha transactivated SOD1 gene
      by 27 fold. The marked transactivation and direct binding of C/EBP alpha to the
      SOD1 promoter were confirmed by deletion analyses and mobility shift assays.
      These results suggested that C/EBP alpha plays a major role in the tissue
      distribution of SOD1.

PMID- 9013902
TI  - Induction of phosphotyrosine in the gap junction protein, connexin43.
AB  - The protein-tyrosine phosphatase inhibitors pervanadate, permolybdate, H2O2, and
      to a much lesser extent vanadate, increased the amount of cellular
      phosphotyrosine and induced tyrosine phosphorylation of connexin43 (Cx43) in
      early passage hamster embryo fibroblasts. The presence of phosphotyrosine in Cx43
      immunoprecipitates from pervanadate-treated cells was shown by a phosphotyrosine
      specific antibody and a phosphotyrosine-specific phosphatase. Pervanadate-induced
      Cx43 tyrosine phosphorylation was further verified by phosphoamino acid analysis,
      while no phosphotyrosine was present in control cells. This is the first
      observation of tyrosine phosphorylation of connexins in normal cells.

PMID- 9013903
TI  - Presidential address: Charles Darwin and vascular surgery.

PMID- 9013904
TI  - Prosthetic above-knee femoropopliteal bypass grafting: results of a multicenter
      randomized prospective trial. Above-Knee Femoropopliteal Study Group.
AB  - PURPOSE: There are excellent arguments in favor of the preferential use of
      prosthetic grafts above the knee for the treatment of infrainguinal occlusive
      disease. This approach has been popularized on the basis of the seemingly
      acceptable results when using polytetrafluoroethylene (PTFE). However, in many
      centers, knitted Dacron polyester has been used in these patients, and there are
      several studies that show equivalent and, in some, superior results with Dacron
      when compared with PTFE. The purpose of this study was to examine these results
      in a definitive way. METHODS: A randomized prospective trial in eight clinical
      academic centers in the United States and Canada was initiated in 1991. Two
      hundred forty-four patients eligible for such a study, by virtue of criteria
      extant in each institution at the time, were centrally randomized. They underwent
      placement of either a knitted Dacron polyester graft impregnated with collagen or
      a thin-wall expanded reenforced PTFE graft to the above-knee popliteal artery,
      usually from the common femoral artery. They were frequently observed by protocol
      for as long as 5 years by a physical examination noninvasive hemodynamic study,
      including duplex scanning in many instances. Continuing patency was noted, as
      were other potential adverse outcome events. The data were analyzed by the log
      rank test for cumulative patency and expressed as Kaplan-Meier curves. Data were
      further analyzed with a Cox proportional hazards model. RESULTS: There were no
      differences in graft groups in demographic or comorbid factors. The procedural
      mortality rate was zero, and the morbidity rate was low (6.5%). The long-term
      patient survival rate was excellent (77% at 3 years). At the end of these years,
      no statistical significance in primary or secondary patency rates was observed
      between the two grafts (primary patency rate, 62% +/- 14.4% for Dacron; 57% +/-
      15.5% for PTFE). No unexpected adverse outcomes on limb status were noted.
      Patency rates in both graft groups were inferior in patients who received small
      grafts (5 to 6 mm vs 7 to 8 mm; hazards ratio, 4.15) and younger (<65 years)
      smoking patients. CONCLUSIONS: The fact that these two prosthetic grafts
      performed in equivalent fashion in a controlled, well-conducted prospective study
      is not surprising in spite of the previous work that suggested differences. If
      the preferential use of synthetic bypass grafts above the knee is to be used, it
      should be restricted to older nonsmokers with favorable anatomy. In that
      instance, the choice of graft material will depend on handling characteristics
      and cost. Above-knee prostheses should be only selectively used in younger,
      smoking patients, and graft size should be carefully considered in patients who
      undergo this operation.

PMID- 9013905
TI  - Impact of arterial surgery and balloon angioplasty on amputation: a population
      based study of 1155 procedures between 1973 and 1992.
AB  - BACKGROUND: Limited population-based data are available on trends in the
      incidence of arterial surgery, balloon angioplasty, and amputation for arterial
      occlusive disease of the legs over the past two decades. METHODS: We identified
      all elective and emergency arterial operations, balloon angioplasty procedures,
      and amputations performed for all residents of a defined community, Olmsted
      County, Minn., between 1973 and 1992. We focused on gender mix, type of
      procedure, and secular trends in utilization. RESULTS: A total of 1155 procedures
      were performed, including 733 arterial surgical procedures, 59 balloon
      angioplasty procedures, and 363 amputations (288 major and 75 minor). Emergency
      procedures were performed in 12%. Suprainguinal inflow procedures were the most
      common arterial reconstruction (60%) compared with infrainguinal procedures
      (40%). The incidence of all revascularization procedures increased in the first
      decade but reached a plateau after 1985. Utilization rates of revascularization
      procedures from 1988 to 1992 were higher for men (141.9/100,000 person-years [p
      yr]) than women (57.4/100,000 p-yr.). Angioplasty (17.0/100,000 p-yr) rates
      lagged behind surgery until 1985, but tripled in the past 10 years and have not
      yet reached a plateau. Although minor amputation rates remain unchanged in 20
      years, major amputation rates have been reduced by 50% from 36.7/100,000 p-yr
      between 1973 and 1977 to 19.0/100,000 p-yr from 1988 to 1992. CONCLUSIONS: From
      this long-term population-based analysis (1973 to 1992), we conclude that
      increased vascular surgery and balloon angioplasty rates have coincided with a
      significant reduction in major amputation rates in the past 10 years.

PMID- 9013906
TI  - Pulmonary embolism is associated with the combination of isolated calf vein
      thrombosis and respiratory symptoms.
AB  - PURPOSE: Overall prevalence of pulmonary embolism (PE) in patients with deep
      venous thrombosis (DVT) isolated to calf veins is low. However, the prevalence of
      PE in the subgroup of patients with respiratory symptoms and isolated calf vein
      thrombosis (CVT) is unknown. Such information is important in determining whether
      patients with CVT only and respiratory symptoms should undergo evaluation for PE.
      The purpose of this study was to determine the prevalence of PE in patients with
      respiratory symptoms and isolated CVT. METHODS: From 1992 through 1994, all
      patients assessed by duplex scanning for lower extremity DVT were reviewed, and
      those found to have isolated CVT and lower extremity or respiratory symptoms were
      identified. Patients who had respiratory symptoms or later developed respiratory
      symptoms in addition to lower extremity symptoms underwent pulmonary angiography
      or ventilation/perfusion (V/Q) scanning. Positive results on pulmonary
      arteriograms or "high probability" V/Q scans were considered diagnostic of PE.
      RESULTS: There were 105 patients with isolated CVT and symptoms. Twenty-six
      patients had respiratory symptoms; nine (35%) had PE and two died. Seventy-nine
      patients had only lower extremity complaints; five later developed respiratory
      symptoms. All five had PE and none had progression of CVT on repeat duplex
      scanning. Neither age, gender, prior DVT/PE, obesity, pregnancy, medication,
      known malignancy, smoking, recent surgery, or trauma predicted PE. CONCLUSIONS:
      Patients with respiratory symptoms and duplex diagnosed isolated CVT have a high
      prevalence of PE and require pulmonary angiographic or V/Q scanning to rule out
      PE.

PMID- 9013907
TI  - Results of percutaneous transluminal angioplasty for atherosclerotic renal artery
      stenosis: a follow-up study with duplex ultrasonography.
AB  - PURPOSE: The short and long-term anatomic results of percutaneous transluminal
      renal angioplasty (PTRA) in the treatment of atherosclerotic renovascular disease
      have been poorly documented because of a lack of follow-up arteriography. The
      purpose of this study was to evaluate the anatomic results of PTRA with serial
      duplex examinations. METHODS: The records of 41 patients who underwent 52 primary
      PTRA procedures and had subsequent duplex follow-up of at least 6 months were
      reviewed. After PTRA, renal arteries were classified as normal, < 60% stenosis, >
      or = 60% stenosis, or occluded on the basis of previously validated duplex
      criteria. RESULTS: The study group included 26 men and 15 women with a mean age
      of 65 years, who were observed for a mean interval of 34 months. Endovascular
      stents were placed in 12 of the 52 arteries. The initial post-PTRA renal artery
      stenosis classification (based on arteriography or duplex scan) was normal in 23,
      < 60% in 19, and > or = 60% in 10. The cumulative incidence of restenosis from
      normal to > or = 60% was 13% at 1 year and 19% at 2 years. The cumulative
      incidence of restenosis from < 60% to > or = 60% was 44% at 1 year and 55% at 2
      years. The cumulative incidence of progression from > or = 60% to occlusion was
      10% at 2 years. Although 83% of the 12 stented arteries and only 33% of the 40
      nonstented arteries were normal immediately after PTRA, after 1 year the stented
      renal arteries showed a 44% restenosis rate, whereas the nonstented renal
      arteries showed a 18% restenosis rate (p = 0.087). CONCLUSIONS: Restenosis after
      PTRA for atherosclerotic disease is relatively common and correlates with the
      initial anatomic result. Although PTRA with stent placement yields superior
      immediate technical results, the high early restenosis rate is disturbing.

PMID- 9013908
TI  - Clinical follow-up rather than duplex surveillance after carotid endarterectomy.
AB  - PURPOSE: The value of duplex surveillance and the significance of contralateral
      carotid disease after endarterectomy have been assessed. METHODS: Three hundred
      five patients were observed prospectively after carotid endarterectomy for a
      median time of 36 months (range, 6 to 96 months), with duplex surveillance
      performed at 1 day; 1 week; 3, 6, 9, and 12 months; and then each year after
      endarterectomy. RESULTS: Thirty patients (10%) had ipsilateral symptoms (13
      strokes, 17 transient ischemic attacks [TIAs]) at a median time of 6 months
      (range, 0 to 60 months). Life table analysis demonstrated that ipsilateral stroke
      was equally common for patients who had > or = 50% restenosis (3% at 36 months)
      and those who did not (6% at 36 months, p > 0.5). Twenty-three patients (8%)
      developed symptoms (stroke 5, TIA 14) attributable to the contralateral carotid
      artery at a median time of 9 months (range, 0 to 36 months) after endarterectomy.
      By life table analysis, 40% of patients with 70% to 99%, 6% with 50% to 69%, 1%
      with < 50% contralateral internal carotid stenosis, and 5% with contralateral
      carotid occlusion at the time of endarterectomy had a contralateral TIA in the 36
      months after endarterectomy (p < 0.01). However, contralateral stroke was not
      significantly more common for patients with severe contralateral internal carotid
      stenosis demonstrated at the time of endarterectomy (< 50% stenosis, 0%; 50% to
      69%, 3%; 70% to 99%, 7%; occlusion, 6% stroke rate at 36 months). Seven of the 32
      patients who developed progression of contralateral disease had a TIA, compared
      with 11 of 227 patients who did not develop progression of contralateral disease
      (p < 0.01). None of the 12 patients who progressed from a < 70% to a 70% to 99%
      contralateral stenosis had a stroke. CONCLUSIONS: After carotid endarterectomy
      restenosis is rarely associated with symptoms; contralateral stroke is rare and
      is not associated with progressive internal carotid artery disease suitable for
      endarterectomy. This study has shown no benefit from long-term duplex
      surveillance after carotid endarterectomy. Selective clinical follow-up of
      patients who have high-grade contralateral stenoses would appear more
      appropriate.

PMID- 9013909
TI  - Immunocytochemical determination of cell type and proliferation rate in human
      vein graft stenoses.
AB  - PURPOSE: Vascular reconstructions are prone to fail as a result of the
      development of stenotic lesions, which have historically been attributed to
      myointimal hyperplasia. In animal models, these lesions are associated with
      marked proliferative smooth muscle cell (SMC) response to vascular injury.
      However, recent studies using sensitive immunocytochemical techniques in human
      lesions have generally failed to detect significant cellular proliferation. To
      clarify the role of cellular proliferation in humans, we characterized the
      cellular composition and proliferative index of 14 early infrainguinal vein graft
      stenoses. METHODS: All infrainguinal vein grafts at our institution are
      prospectively enrolled in a duplex surveillance protocol, the details of which
      have been previously reported. Among 98 grafts placed within the last year, 11
      patients were identified with 14 progressive, focal, high-grade lesions that met
      previously established threshold criteria for prophylactic revision to prevent
      graft thrombosis. Lesions were first detected from 1 week to 7 months after
      surgery and were removed and replaced with segmental interposition grafts (1.5 to
      10 months). Freshly excised lesions were placed in Methyl Carnoy's fixative,
      paraffin embedded, and serially sectioned. The cellular composition of each
      lesion was determined with cell-specific immunochemical reagents: alpha SMC
      actin, von Willebrand factor (endothelial cell), CD 68 (macrophage), and CD 45RB
      (monocyte). Actively proliferating cells were identified using antibody to
      proliferating cell nuclear antigen (PCNA). The identity of PCNA-positive cells
      was determined by double-label immunocytochemical staining, and the proliferative
      index (PCNA-positive cells/total cells x 100) was calculated by computer-assisted
      counts of representative gridded cross-sections of each lesion. RESULTS: All
      excised lesions demonstrated marked thickening with severe luminal encroachment
      and were highly cellular, with a predominance of alpha SMC actin+. Endothelial
      cells on the blood flow surface were present to a variable degree, and seven
      lesions exhibited striking numbers of macrophages and monocytes. The latter cell
      types were most abundant near microvessels in the deep neointima and adventitia.
      Active cellular proliferation was identified primarily in SMCs, with a mean PCNA
      index of 1.34%. However, significant PCNA reactivity was not limited to SMCs, but
      was also identified in macrophages and monocytes, particularly in lesions greater
      than 3 months old. CONCLUSIONS: Previous immunocytochemical studies of human
      coronary restenosis atherectomy specimens have generally detected low rates of
      cellular proliferation (0.5%), but these lesions may not truly represent
      myointimal hyperplasia, rather a mixture of atherosclerosis, thrombosis, and
      "restenosis." In contrast, the present study of early human vein graft lesions
      detected by duplex surveillance indicates that significant cellular proliferation
      occurs, although rates are lower than those obtained in animals such as the rat
      carotid injury model. In addition, although SMCs are the predominant
      proliferating cell type in human vein grafts, our identification of proliferating
      monocytes and macrophages raises the question of the contribution of an
      inflammatory component to the development of human lesions. The present study
      represents the first report of PCNA determination in a series of human
      infrainguinal vein grafting procedures.

PMID- 9013910
TI  - High incidence of restenosis/reocclusion of stents in the percutaneous treatment
      of long-segment superficial femoral artery disease after suboptimal angioplasty.
AB  - PURPOSE: To evaluate the efficacy of intravascular stents used to treat long
      segment stenoses and occlusions of the superficial femoral artery (SFA) after
      suboptimal angioplasty. METHODS: Fifty-eight limbs in 55 patients who underwent
      stenting of the SFA were identified from a vascular registry. Indications for
      stent placement after suboptimal PTA included flow-limiting dissection, residual
      pressure gradient (>15 mm Hg) or stenosis (>30%), or failure to establish initial
      patency. Lesion length ranged from 6 to 35 cm (mean, 16.5 cm). Endpoints for
      primary patency were: restenosis of >50%, reocclusion, or diminution of the
      postprocedure ankle-brachial index greater than 0.15. RESULTS: The mean ankle
      brachial index improved from 0.48 +/- 0.19 to 0.71 +/- 0.23 (p = 0.001). Primary
      patency rates by Kaplan-Meier estimates at 1 month, 6 months, and 1 year were
      88%, 47%, and 22%, respectively. Secondary patency rates were 94% at 1 month, 59%
      at 6 months, and 46% at 1 year. The median time to reaching an endpoint of
      restenosis or reocclusion was 6 months primarily and 9 months secondarily.
      Clinical improvement at the time of latest follow-up occurred in 56% of patients
      (mean, 13.8 months). Periprocedural complications occurred in 24.5% of patients
      with the first intervention. The only factor that favorably influenced outcome
      was improvement in clinical category after the procedure (p = 0.001).
      CONCLUSIONS: There was a high incidence of restenosis and reocclusion with long
      segment SFA disease that required stents to achieve initial success. Despite
      close surveillance and reintervention, anatomic patency at 1 year was poor.
      However, clinical benefit was maintained in the majority of patients. The outcome
      was similar in the claudication population compared with those who had limb
      threatening ischemia. Percutaneous revascularization of long-segment SFA disease
      requiring stents should be reserved for patients with critical limb ischemia for
      which no reasonable surgical alternative exists.

PMID- 9013911
TI  - Utility of clinical pathway and prospective case management to achieve cost and
      hospital stay reduction for aortic aneurysm surgery at a tertiary care hospital.
AB  - PURPOSE: We reviewed our experience with a clinical pathway instituted in
      December 1993 for all nonurgent abdominal aortic aneurysm (AAA) surgery. METHODS:
      We analyzed a reference group of 49 consecutive pre-pathway AAA patients (group
      I) and the 44 patients enrolled in the first year of the pathway (group II). On
      the basis of the interim review of data collected during the first year, pathway
      modifications were made, and 34 patients enrolled after these modifications
      (group III) were also analyzed. RESULTS: Comparison of groups I and II showed
      that institution of the pathway resulted in a marginally significant reduction in
      mean charges of 14.7% (p = 0.09), and a slight fall in mean length of stay (LOS)
      (13.8 vs 13.1 days, NS) and mortality rate (4.1% vs 2.3%, NS). For group II, a
      significant correlate (p < 0.05) of increased charges was fluid overload as
      diagnosed by chest radiograph. This recognition led to active efforts to reduce
      perioperative fluid administration. Comparison of groups II and III revealed that
      the practice modifications led to marked reduction in the incidence of fluid
      overload (73% vs 24%; p < 0.01), mean charges (30.4% reduction; p < 0.05), mean
      LOS (13.1 vs 10.2 days; p < 0.05), and median LOS (11 vs 8 days). Multiple
      regression analysis of all pathway patients showed that preoperative renal
      insufficiency is a significant predictor of both increased LOS (p < 0.01) and
      charges (p < 0.01), but that age, sex, and coronary disease were not predictive.
      Of the postoperative parameters analyzed, important correlates of increased
      charges were acute renal failure (p < 0.01) and fluid overload (p < 0.01).
      CONCLUSIONS: Institution of a clinical pathway for AAA repair resulted in
      significant charge reduction and a slight reduction in stay. Practice
      modifications based on interim data analysis yielded further significant
      reductions in charges and LOS, with overall per-patient charge savings (group I
      vs III) of 40.6% (p < 0.05) and overall LOS reduction of 3.5 days (p < 0.05). The
      reduction in actual charges was seen despite an overall increase in the hospital
      rate structure. Comparing groups I, II, and III, we found no indication of
      increasing mortality rate. Ongoing analysis has identified correlates of
      increased charges, potentially permitting identification of high-cost subgroups
      and more focused cost-control efforts. Rather than restricting management,
      clinical pathways with periodic data analysis may improve quality of care.

PMID- 9013912
TI  - Safety, feasibility, and early efficacy of subfascial endoscopic perforator
      surgery: a preliminary report from the North American registry.
AB  - PURPOSE: The North American Subfascial Endoscopic Perforator Surgery (NASEPS)
      Registry was established to evaluate the safety, feasibility, and efficacy of
      minimally invasive endoscopic Linton operations for treatment of chronic venous
      insufficiency. METHODS: Retrospective analysis was performed on the clinical data
      of 151 patients who underwent attempt at 158 SEPS in 17 medical centers in the
      United States and Canada between June 1993 and February 1996. RESULTS: SEPS was
      completed on 155 limbs of 148 patients, 81 male and 67 female (mean age, 56
      years; range, 27 to 87 years). Three procedures were aborted. Seven patients had
      bilateral procedures (data from one limb were analyzed). One hundred four limbs
      (70%) had active ulcers, and 22 (15%) had healed ulcers. A single endoscopic port
      without insufflation was used in 66 procedures (45%) and laparoscopic
      instrumentation, with two or three ports, in 82 (55%), with CO2 insufflation in
      78 (53%). A tourniquet was used on 112 patients (76%). Concomitant venous
      procedures were performed in 106 patients (72%; saphenous stripping in 71, high
      ligation in 17, varicosity avulsion in 85). No early deaths or thromboembolism
      occurred. Complications included wound infections (9), superficial
      thrombophlebitis (5), cellulitis (4), and saphenous neuralgia (10). Seven
      patients with wound infection had open ulcers; nine of 10 with neuralgia had
      concomitant procedures. A roll-on tourniquet caused skin necrosis in one patient.
      The clinical score improved from 9.4 to 2.9 after surgery (p < 0.0001). Mean
      follow-up was 5.4 months; 31 patients had > or = 6 months follow-up. Ulcers
      healed in 88% (75 of 85); recurrence or new ulcer was reported in 3% (4 of 120).
      CONCLUSIONS: The SEPS modified Linton operation appears safe, with no
      postoperative deaths or early thromboembolism. Wound infection after SEPS remains
      important. Early results indicate rapid ulcer healing. Prospective evaluation of
      long-term results is warranted.

PMID- 9013913
TI  - Alternative approach for management of infected aortic grafts.
AB  - PURPOSE: Prosthetic infection after aortic reconstructive surgery historically
      has been treated with extraanatomical bypass, graft excision, and aortic stump
      closure, but at the cost of substantial mortality and amputation rates.
      Alternatives to this strategy include in situ prosthetic replacement in the
      infected area, as well as autogenous reconstructions. Inherent to all of these
      procedures, however, is either the creation of an aortic stump, which carries a
      significant risk of subsequent blowout, or the placement of a bypass conduit in
      the infected field, thereby maintaining the potential for subsequent infectious
      complications. To avoid such problems, we have used retroperitoneal in-line
      aortic bypass with polytetrafluoroethylene through dean tissue planes. METHODS:
      Since 1987 we have treated 16 graft infections in this manner. The surgical
      approach consisted of obtaining retroperitoneal proximal aortic control outside
      of the infected field (above or below the renal arteries), followed by infrarenal
      division and oversewing of the distal aorta. A polytetrafluoroethylene bifurcated
      graft was then sewn to the proximal aorta and tunnelled through the psoas sheath
      laterally to the profunda femoris artery on the ipsilateral side and via the
      space of Retzius to the contralateral appropriate femoral vessel, so as to avoid
      any contact with the infected areas. After the closure of the wounds, a plastic
      barrier was placed over all incisions and the patient was placed supine. The old
      infected graft was removed transperitoneally. Extensive cultures were taken at
      various sites to demonstrate no cross-contamination. RESULTS: All patients were
      followed-up clinically and with tagged white cell scans at 6-month intervals.
      There were no immediate postoperative deaths and no amputations. One patient had
      a myocardial infarction and died at 5 months, and a second patient died at 2
      months. Of the remaining 14 patients, none had recurrent sepsis and all have had
      negative Indium-labeled white cell scans in follow-up. Eleven (78%) are still
      alive, with a mean follow-up of 32 months (range, 20 to 106 months). CONCLUSIONS:
      In-line aortic bypass for treatment of aortic graft infections yields excellent
      results and has become our treatment of choice in dealing with this difficult
      problem.

PMID- 9013914
TI  - Reduction in aortic aneurysm size: early results after endovascular graft
      placement. EVT Investigators.
AB  - PURPOSE: Previous reports demonstrate initial technical success with
      transluminally placed endovascular grafts (TPEG) for the treatment of abdominal
      aortic aneurysms. However, long-term changes in the size of the aorta and
      aneurysmal segments are unknown. The purpose of this study was to determine
      aortic dimensions at several levels by computed tomographic (CT) scans 1 year
      after TPEG. METHODS: Thirty-four patients underwent TPEG with 1-year CT scans.
      Patients were divided into three groups: group I, no perigraft leak; group II,
      early perigraft leak that sealed during the first year; and group III, persistent
      perigraft leak. Aortic minor and major diameters, perimeter, and area were
      measured at four locations: the celiac aorta, proximal neck, maximal aneurysm
      size, and distal neck. RESULTS: There were 32 men and two women, with a mean age
      of 73 +/- 8 years. In group I there were 20 patients (58%), and groups II and III
      had seven patients (21%) each. The overall mean aneurysm minor diameter decreased
      from 4.79 +/- 0.68 cm at implantation to 4.39 +/- 0.86 cm at 1 year (p < 0.0001).
      The aneurysm sac decreased by 0.63 +/- 0.58 cm in group I, and by 0.34 +/- 0.24
      cm in group II. In group III, however, the aneurysm sac increased by 0.19 +/-
      0.21 cm. Aneurysm size change did not correlate with inferior mesenteric or
      lumbar artery patency. The dimensions of the celiac aorta and proximal neck did
      not change significantly. However, diameter of the distal neck enlarged by 0.12
      +/- 0.27 cm (p < 0.01). CONCLUSIONS: TPEG exclusion is associated with reduction
      of aneurysm size 1 year after implantation. Expansion of the aneurysms occurred
      with persistent perigraft leak. The aortic size at the celiac artery and proximal
      neck did not change. Dilation of the distal neck was minor but requires further
      long-term follow-up to determine clinical significance.

PMID- 9013915
TI  - The glycoprotein IIb/IIIa antagonist c7E3 inhibits platelet aggregation in the
      presence of heparin-associated antibodies.
AB  - PURPOSE: Heparin-associated antibodies (HAAb), in the presence of heparin, can
      cause platelet activation and aggregation. The purpose of this study was to
      assess whether a platelet glycoprotein (GP) IIb/IIIa receptor antagonist, c7E3,
      would inhibit platelet aggregation in the presence of HAAb. If aggregation is
      inhibited by c7E3, enzyme-linked immunosorbent assays (ELISA) would be done to
      determine whether c7E3 interfered with the binding of heparin and the HAAb.
      METHODS: HAAb-positive plasmas from 21 patients (determined by platelet
      aggregation assays) were studied. Normal donor platelet-rich plasmas (PRP) were
      incubated (1 minute) with either saline solution or 3 microg/ml of c7E3. Platelet
      poor plasma from patients with HAAb and one of three sources of heparin (25
      microl, 10 U/ml; porcine heparin, bovine heparin, and low molecular weight
      heparin [enoxaparin]) were added to the PRP mixture. Aggregation was determined
      using a platelet aggregometer by measuring time to aggregation, the slope of the
      aggregation curve, and the percent change in optical density. RESULTS: Platelet
      aggregation occured in 100%, 100%, and 95% of the saline solution incubations
      exposed to porcine heparin, bovine heparin, and enoxaparin, respectively.
      Incubation with c7E3 caused 100% inhibition of platelet aggregation in plasma
      exposed to porcine heparin, bovine heparin, and enoxaparin. The optical density
      curves obtained from the ELISA, which were dependent on the binding of HAAb to
      heparin, were not significantly different when c7E3 was compared to buffer alone.
      CONCLUSIONS: The GP IIb/IIIa receptor antagonist, c7E3, inhibits HAAb-induced
      platelet aggregation via a mechanism that does not appear to interfere with the
      binding between heparin and HAAb. Clinical trials are warranted to assess whether
      GP IIb/IIIa antagonists may allow patients with HAAb to safely receive heparin.

PMID- 9013916
TI  - Carotid surgery: the past is prologue. The John Homans lecture.

PMID- 9013917
TI  - Same-day admissions and other cost-saving strategies for elective aortoiliac
      surgery.
AB  - PURPOSE: We retrospectively analyzed whether same-day admissions and other
      resource utilization methods for patients undergoing elective infrarenal
      aortoiliac surgery (AoIS) were safe and cost-effective. METHODS: Morbidity and
      mortality rates and costs were compared between 71 patients admitted before the
      day of surgery (group I) and 57 patients admitted the day of surgery (group II)
      who underwent elective AoIS between July 1, 1992, and December 31, 1995. After
      January 1, 1994, a concerted effort was made to decrease hospital costs by
      performing out-patient preoperative assessment, admitting patients the morning of
      surgery, and planning early discharge through implementation of clinical
      pathways. Patients were excluded (total, 33; 20%) from analysis if they were
      admitted before the day of surgery for intravenous hydration (5), optimizing
      cardiac function (4), or prolonged preoperative antibiotics (2), or if they
      required emergency surgery (10) or were transferred from another service or
      hospital (12). After exclusion, there were no significant differences (p > 0.05)
      between groups I and II in terms of age, sex, race, diabetes, hypertension,
      pulmonary disease, cardiac disease, renal insufficiency, type of incision
      (midline or retroperitoneal), indication for surgery (aneurysm or occlusive
      disease), or inflow site (aorta or common iliac artery). RESULTS: There were no
      significant differences between groups I and II in terms of mortality rate (0%);
      cardiac (1.4% [1/71] vs 0%), pulmonary (9.9% [7/71] vs 5.3% [3/57]), or renal
      (1.4% [1/71] vs 0%) complications; or readmission rates within 30 days (5.6%
      [4/71] vs 5.2% [3/57]), respectively (p > 0.05). There were significant decreases
      in length of hospital stay (mean, 6.4 vs 11.2 days; p < 0.0001) and hospital cost
      per patient ($34,198 vs $45,694; p = 0.001) for group II compared to group I,
      respectively. CONCLUSIONS: The majority of patients who require elective
      infrarenal aortoiliac surgery can be admitted the day of surgery and undergo
      early discharge with significant hospital cost savings and without apparent
      increase in morbidity or mortality rates.

PMID- 9013918
TI  - Magnetic resonance angiography of the aortic arch.
AB  - Duplex ultrasound and magnetic resonance angiographic (MRA) studies are the
      principal noninvasive methods for evaluation of extracranial occlusive disease in
      patients at risk for stroke, but each has limited ability to diagnose aortic arch
      and arch vessel disease. Recent favorable reports of the nonnephrotoxic contrast
      agent Gadolinium (Gd) being used to enhance MRA images of the abdominal aorta
      prompted us to examine its utility for the aortic arch vessels. Prospectively, 28
      patients with suspected carotid or arch vessel disease were imaged by contrast
      arteriographic examination and MRA + Gd of the aortic arch within 30 days of each
      other. One (for contrast arteriograms) or two (for MRA) blinded readers measured
      stenoses with the contrast arteriograms as the standard. A total of 196 arch
      vessels containing 58 stenoses and four occlusions (by arteriogram) were examined
      with each method. Interobserver agreement for interpretation of MRA studies was
      substantial (kappa = 0.68). MRA detected all anatomic anomalies (e.g., bovine
      arch). The correlation of MRA with arteriographic scans for arch vessel stenoses
      > 50% was sensitivity, 73% (readers 1 and 2); specificity, 98% (reader 1), 89%
      (reader 2); positive predictive value, 73% (reader 1), 89% (reader 2); negative
      predictive value, 98% (readers 1 and 2); accuracy, 97% (reader 1), 98% (reader
      2). MRA + Gd is an accurate new noninvasive imaging method for detection of
      significant aortic arch disease. In its current state of development, however, it
      cannot obviate the need for contrast arteriographic examination.

PMID- 9013919
TI  - Is preoperative cardiac evaluation for abdominal aortic aneurysm repair
      necessary?
AB  - PURPOSE: It is reported that 25% to 50% of patients with abdominal aortic
      aneurysms (AAA) have severe coronary artery disease (CAD) and should undergo an
      aggressive cardiac workup before AAA repair. In contrast, it has been our policy
      that patients referred for AAA repairs undergo no cardiac testing before surgery.
      METHODS: This report reviews the last 113 consecutive patients who underwent
      elective AAA repair by the senior author using this policy. Seventy-four patients
      (group A) had only an electrocardiogram before surgery. The remaining 39 patients
      (group B) were referred having already had additional testing that included a
      thallium stress test (n = 20), echocardiogram (n = 18), multiple gated
      acquisition (MUGA) scan (n = 3), cardiac catheterization (n = 8), or some
      combination of these. RESULTS: There was no statistical difference between group
      A and group B with regard to age, sex, tobacco use or history of coronary artery
      disease, diabetes mellitus, stroke (CVA), hypertension, peripheral vascular
      disease, or chronic obstructive pulmonary disease. Group B more commonly had a
      history of myocardial infarction (41% vs 19%, p < 0.03) and congestive heart
      failure (23% vs 7%, p < 0.03). During surgery there was no significant
      differences in blood loss, transfusion requirements, or operative times. There
      were no myocardial infarctions in group A and two (5.1%) in group B, which was
      not significantly different. Other complications, such as CVA, renal failure,
      pulmonary failure, pneumonia, wound infection, and hemorrhage, were not
      significantly different between the two groups. Postoperative hospital stay was
      not significantly different. There were three deaths in the entire series (2.7%),
      and only one in group B was cardiac-related in a patient with known end-stage
      cardiac disease and a symptomatic 8 cm AAA. CONCLUSIONS: These data indicate that
      most patients with AAA can safely undergo repair with no cardiac workup and that
      cardiac workup before AAA repair contributes little information that impacts on
      treatment or final clinical outcome. We conclude that cardiac testing in
      preparation for AAA repair is not usually necessary and that intraoperative
      hemodynamic management may be the most important variable in determining outcome.

PMID- 9013920
TI  - Elevations of tissue-type plasminogen activator and differential expression of
      urokinase-type plasminogen activator in diseased aorta.
AB  - PURPOSE: Elevations of plasmin have been implicated in the pathogenesis of
      abdominal aortic aneurysms (AAA) because of its ability to digest extracellular
      matrix proteins. Plasminogen activators regulate the conversion of plasminogen to
      plasmin. Tissue-type plasminogen activator (tPA) is more important in modulation
      of fibrinolysis, and urokinase-type plasminogen activator (uPA) is predominant in
      tissue remodeling. The purpose of this study was to determine the levels of
      plasminogen activators in diseased aorta because they may be responsible for the
      increased plasmin levels previously described in AAA. METHODS: Levels of tPA and
      uPA in AAA, occlusive, and normal (organ donor) aorta were studied in tissue
      explant supernatants. Supernatant tPA and uPA levels were measured with an enzyme
      linked immunosorbent assay. Northern analysis was used to quantitate uPA
      messenger RNA (mRNA) levels in aortic tissue. RESULTS: Levels of tPA in the
      supernatants were similar in occlusive (20 +/- 4 ng/ml) and AAA (23 +/- 8) aorta,
      but threefold higher than in normal aorta (7 +/- 5; p < 0.005 for normal vs
      occlusive and p < 0.001 for normal vs AAA). In contrast, uPA supernatant levels
      were differentially expressed, with the highest level existing in AAA (9.7 +/-
      2.7 ng/ml), followed by occlusive (4.9 +/- 3.5), and the lowest levels in normal
      aorta (1.2 +/- 0.7; p < 0.05 for normal vs occlusive, p < 0.001 for normal vs
      AAA, and p < 0.005 for occlusive vs AAA). Inhibition of protein or RNA synthesis
      by addition of cyclohexamide or actinomycin D, respectively, revealed no
      significant difference between treated and control supernatants, suggesting that
      the increases were caused by protein release rather than active synthesis. Levels
      of uPA mRNA followed the same trend as the supernatant uPA levels (AAA 1.07 +/-
      0.54, occlusive 0.54 +/- 0.08, and normal aorta 0.01 +/- 0.01). CONCLUSIONS:
      Levels of tPA were similar in aneurysmal and occlusive aorta, but exhibited a
      threefold increase over normal aorta, suggesting that the elevations of tPA are
      associated with the arteriosclerosis present in both aneurysmal and occlusive
      disease. Differences in uPA levels were significant between all three groups,
      with the highest levels in AAA and the lowest levels in normal specimens.
      Northern analysis of uPA mRNA followed the same trend, suggesting that the
      increase in uPA may be regulated at the level of transcription. As uPA plays an
      important role in tissue remodeling, our findings may also reflect the relative
      tissue repair activities in these three types of specimens and may explain the
      previously reported increased levels of plasmin seen in AAA.

PMID- 9013921
TI  - Early results of endovascular aortic aneurysm surgery with aortouniiliac graft,
      contralateral iliac occlusion, and femorofemoral bypass.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of endovascular
      aortic aneurysm repair with use of an aortouniiliac graft secured with self
      expanding (Gianturco) stents. METHODS: Thirty patients with a median age of 72
      years (age range, 52 to 86 years) and aneurysm diameter of 6.0 cm (range, 4.0 to
      9.0 cm) were treated with an aortouniiliac endovascular graft. Of these 30
      procedures, 28 were carried out electively and two as emergencies for leaking
      aneurysm. Of the 30 patients, 21 (70%) were considered to be at high risk for
      open surgery. A modified Gianturco stent, Dacron graft, and Wallstent were used
      for these procedures. RESULTS: Endovascular repair was successfully carried out
      in 25 of 30 (83.3%) patients. All these patients were mobile and had resumed a
      normal diet within 48 hours of the procedure. The overall 30-day mortality rate
      was two in 30 (6.6%), but it was one in 28 (3.5%) for the elective cases; all
      deaths occurred in the group at high risk for surgery. Other complications
      encountered within 30 days of procedure included myocardial infarction in one
      patient, pneumonia in two patients, homonymous quadrantanopia in one patient, and
      colonic ischemia in one patient, giving an overall morbidity rate of four in 30
      (13.3%). At a median follow-up of 4 months (range, 1 to 13 months), 27 of 30
      (90%) patients remain alive and well. CONCLUSION: Endovascular aortouniiliac
      repair of abdominal aortic aneurysm with Gianturco stent is feasible in both
      elective and emergency situations. It appears to be minimally traumatic, and the
      majority of patients deemed to be at high risk for open surgery can safely
      undergo endovascular repair. However, data on more patients with longer follow-up
      is required to determine its role in the management of abdominal aortic aneurysm.

PMID- 9013922
TI  - Long-term results with axillo-axillary bypass grafts for symptomatic subclavian
      artery insufficiency.
AB  - PURPOSE: The surgical treatment for patients with a subclavian steal is
      controversial, especially for patients with coexisting severe carotid stenosis.
      This study determines the long-term efficacy of axillo-axillary bypass grafts in
      patients with and without a simultaneous carotid endarterectomy. METHODS: The
      axillo-axillary bypass was done in 39 patients who were monitored for 5.8 +/- 3.9
      years. Fifteen of these patients with severe carotid artery disease had a carotid
      endarterectomy done simultaneously. Twenty-four patients had an axillo-axillary
      bypass alone; four of these patients later had a carotid endarterectomy at 0.5 to
      10 years. Graft patency was evaluated at intervals of 6 to 12 months by clinical
      evaluation and noninvasive vascular studies. RESULTS: Ten-year primary and
      secondary patency rates for all axillo-axillary bypass grafts were 88% and 91%,
      respectively. When carotid endarterectomy was done with axillo-axillary bypass,
      these patency rates were 86% and 93%, respectively. Patients with only axillo
      axillary grafts had 10-year primary and secondary patency rates of 89% and 89%,
      respectively. Most patients had complete relief from symptoms of arm ischemia
      (90%) and vertebrobasilar insufficiency (85%). No perioperative mortality or
      permanent neurologic deficit occurred. CONCLUSIONS: Axillo-axillary bypass is a
      safe and effective method for revascularization of the subclavian artery and
      should be considered for patients at high risk.

PMID- 9013923
TI  - Microembolization during endovascular and conventional aneurysm repair.
AB  - PURPOSE: Endovascular aneurysm repair has been advocated as a "minimally
      invasive" alternative to conventional aneurysm surgery. However, because of
      manipulation within the aneurysm sac, endovascular techniques may result in
      massive microembolization. METHODS: In this study lower limb microemboli were
      quantified in 29 patients undergoing conventional (11 straight and 7 bifurcated
      grafts) and endovascular aneurysm repair (8 aortoiliac, 1 straight, and 2
      bifurcated grafts) by insonation of the superficial femoral artery with a 2 MHz
      Doppler probe. Emboli were detected as high-intensity, short-duration signals on
      the background Doppler trace. Differentiation of gaseous emboli from particulate
      emboli was achieved by calculation of the sample volume length (emboli velocity x
      duration = sample volume length) for each embolus (N = 4927). Previous
      experiments had determined that a sample volume length < 1.4 cm represented
      particulate embolization. RESULTS: The number of gaseous, particulate, and total
      emboli were significantly greater in the endovascular group compared with the
      conventional group (p < 0.05). CONCLUSIONS: These data demonstrate that
      peripheral microembolization is significantly higher during endovascular aneurysm
      repair than during conventional surgery. Methods to reduce embolization must be
      developed before endovascular aortic surgery is widely adopted.

PMID- 9013924
TI  - Production of endothelium-derived factors from sodded expanded
      polytetrafluoroethylene grafts.
AB  - PURPOSE: Experiments were designed to determine whether endothelium isolated from
      adipose tissue and sodded onto expanded polytetrafluoroethylene grafts release
      endothelium-derived vasoactive factors. METHODS: Thin-walled expanded
      polytetrafluoroethylene grafts (6 mm internal diameter, 6 cm length, 30 microm
      pore size), one sodded with autogenous endothelial cells, the other unsodded,
      were implanted bilaterally in carotid arteries of 30 male mongrel dogs. Dogs were
      treated with 325 mg aspirin daily. After 6 weeks grafts were excised and perfused
      in a bioassay system. Effluent from the grafts stimulated with either
      acetylcholine, thrombin, adenosine 5-diphosphate, or the calcium ionophore A23187
      was superfused over rings of canine femoral arteries without endothelium
      contracted with phenylephrine. Effluent from the grafts was analyzed by
      radioimmunoassay for thromboxane B2, 6-keto-prostaglandin F1alpha, endothelin-1,
      and C-type natriuretic peptide. RESULTS: Ninety percent of the sodded grafts and
      87% of the unsodded grafts were patent after 6 weeks. Bioassay rings superfused
      with effluent from sodded grafts stimulated with acetylcholine relaxed
      significantly more than rings superfused with effluent from similarly stimulated
      unsodded grafts. Biochemical analysis of the effluent showed an increase in 6
      keto prostaglandin F1alpha and C-type natriuretic peptide and a decrease in
      endothelin-1 and thromboxane B2 release from the sodded compared with the
      unsodded grafts. Scanning electron microscopy showed a continuous layer of
      endothelial cells lining only the sodded grafts. Staining for alpha-actin and
      heavy-chain myosin showed a differentiated layer of smooth muscle below the
      endothelial layer on the sodded grafts. Finally, there was positive staining for
      C-type natriuretic peptide and endothelin-1 in the endothelium of the sodded
      grafts. CONCLUSIONS: These results indicate that endothelial cells of sodded
      expanded polytetrafluoroethylene grafts produce endothelium-derived vasoactive
      factors. In addition, receptor-coupled synthesis/release of these factors is
      retained in sodded endothelial cells.

PMID- 9013925
TI  - Soma-germ cell interactions in Caenorhabditis elegans: multiple events of
      hermaphrodite germline development require the somatic sheath and spermathecal
      lineages.
AB  - Germ cells complete multiple events to form functional oocytes and sperm. In the
      Caenorhabditis elegans hermaphrodite, germ cells develop in proximity to the
      somatic gonad sheath and spermathecal cells. We present evidence from cellular
      laser ablation studies indicating that cells of the somatic sheath and
      spermathecal lineages play critical roles in four events of hermaphrodite
      germline development. (1) Cells of the sheath and spermathecal lineage support
      germline proliferation; ablation of sheath/spermathecal precursor cells reduces
      mitotic proliferation. (2) These cells also play a role in the exit of germ cells
      from the pachytene stage of meiotic prophase and/or gamete differentiation;
      ablation can result in undifferentiated germ cells arrested in pachytene. (3)
      Proximal sheath and distal spermatheca cells are required for ovulation of the
      oocyte. During wild-type ovulation, the mature oocyte is expelled from the gonad
      arm by contraction of the proximal myoepithelial sheath and dilation of the
      distal spermatheca. Ablation of these cells traps mature oocytes in the gonad arm
      where they endomitotically replicate their DNA (the Emo phenotype). (4) Cells of
      the sheath and spermathecal lineage also appear to promote the male germ cell
      fate since ablation of one sheath/spermathecal precursor cell can feminize the
      hermaphrodite germ line. These somatic ablation-induced germline phenotypes
      demonstrate that the somatic gonad is required for multiple events in C. elegans
      germline development. Further, these results suggest that soma to germline cell
      cell interactions in C. elegans are physiological in character (i.e., contraction
      during ovulation) as well as regulatory.

PMID- 9013926
TI  - GATA-2 is a maternal transcription factor present in Xenopus oocytes as a nuclear
      complex which is maintained throughout early development.
AB  - We show that Xenopus oocytes and embryos contain GATA-2, stored in nuclei as a
      non-chromatin-bound complex. Its binding site specificity is different from that
      of GATA-1, having a much higher affinity for the motif with a core GATC sequence.
      This binding site preference was markedly reduced by either release of the factor
      with deoxycholate or purification on a DNA affinity column, suggesting a role for
      a cofactor(s). The identity of the maternal GATA factor was established as GATA-2
      in two ways: (1) binding to an oligonucleotide probe was abolished by inclusion
      of either of two GATA-2 monoclonal antibodies, and (2) a protein of correct
      molecular weight for GATA-2 was detected by immunoblotting with a polyclonal
      antibody raised against a Xenopus GATA-2-specific peptide. Although predominantly
      complexed, some of the oocyte GATA-2 is functional as a transcription factor
      because the transcriptional activity of the chicken betaH-globin promoter
      injected into oocytes was reduced by mutation of either of two GATA binding
      sites. This effect was more pronounced when the stronger of the two sites was
      mutated. Butyrate treatment of oocytes stimulated cap-site initiation by up to 17
      fold with both normal promoter and GATA site mutant constructs, showing that the
      mechanism of butyrate stimulation is not via GATA-2. The possible significance of
      regulating the availability of maternal GATA-2 during early development is
      discussed.

PMID- 9013927
TI  - Transient expression of Dp140, a product of the Duchenne muscular dystrophy
      locus, during kidney tubulogenesis.
AB  - Dystroglycan is a cell surface complex which in muscle links the extracellular
      matrix protein laminin-2 to the membrane associated cytoskeletal protein
      dystrophin. Recently it was found that dystroglycan is also expressed in
      developing epithelial cells. Moreover, antibodies against dystroglycan can
      perturb epithelial cell development in kidney organ culture. Dystroglycan could
      provide a link between the basement membrane and the intracellular space also in
      epithelial cells. However, there is no dystrophin in epithelial cells. By in situ
      hybridization here we show prominent expression of a shorter isoform of
      dystrophin, Dp140, in embryonic kidney tubules. In addition, another isoform,
      Dp71, is expressed by all studied embryonic epithelial cells. Both isoforms share
      the dystroglycan-binding region of dystrophin but lack the region known to bind
      to actin. Here we also characterized monoclonal antibodies against different
      domains of dystrophin and used these to study the distribution of Dp140 protein.
      In embryonic kidney tubules the dystrophin antibody VIA4(2)A3 stained an
      intracellular antigen close to the basal cells. In contrast, no staining was
      observed in adult kidney. We suggest that Dp140 is a structural component during
      kidney tubulogenesis but it may also be involved in signal transduction.

PMID- 9013928
TI  - Broad-complex transcription factors regulate thoracic muscle attachment in
      Drosophila.
AB  - The Broad-Complex, a 20-hydroxyecdysone-regulated gene, is essential for the
      development of many tissues during metamorphosis. In Broad-Complex mutants of the
      rbp complementation group, dorsoventral indirect flight muscles (DVM) are largely
      absent, and the dorsal longitudinal indirect flight muscles, tergotrochanteral
      muscles, and remaining DVM often select incorrect attachment sites. The Broad
      Complex encodes a family of zinc-finger-containing transcription factors, and it
      is hypothesized that Broad Complex proteins containing the Z1 zinc-finger pair
      (BRC-Z1) mediate rbp+ function. We provide additional strong support for this
      hypothesis by showing that heat-shock-induced BRC-Z1 expression rescues the
      thoracic muscle defects of rbp mutants completely. BRC-Z4 induction can also
      rescue the thoracic musculature, but BRC-Z2 and -Z3 can not. Thus, the effect is
      specific to BRC-Z1 and its closest relative, BRC-Z4. Formation of muscle
      primordia from imaginal myoblasts appears normal in rbp mutants. However, the
      myotendinous junctions linking the DVM to the dorsal epidermis are weak, and the
      muscles detach during pupal life and subsequently degenerate. The data indicate
      that rbp mutations disrupt the cell-cell interactions between developing muscles
      and epidermal tendon cells as they recognize and attach to one another. Using a
      BRC-Z1-specific monoclonal antibody, we show that both the developing muscles and
      epidermal tendon cells express BRC-Z1 at the time of pupation, before mutant
      muscles begin to detach. We conclude that 20-hydroxyecdysone acts through the
      Broad-Complex to control the development of thoracic myotendinous junctions.

PMID- 9013929
TI  - Targeted mutations in hoxa-9 and hoxb-9 reveal synergistic interactions.
AB  - Mice were generated with a targeted disruption of the homeobox-containing gene
      hoxb-9. Mice homozygous for this mutation show defects in the development of the
      first and second ribs. In most cases the first and second ribs are fused near the
      point at which the first and second pairs of ribs normally attach to the sternum.
      Abnormalities of the sternum accompany the rib fusions. These include abnormal
      attachment of the ribs to the sternum, a reduction in the number of intercostal
      segments of the sternum, and abnormal growth of the intercostal segments. Over
      half of the homozygous mutants, as well as some heterozygotes, also have an
      eighth rib attached to the sternum. These results show that hoxb-9 plays a
      significant role in the specification of thoracic skeletal elements. To reveal
      potential interactions between the paralogous Hox genes hoxa-9 and hoxb-9, mice
      heterozygous for both mutations were intercrossed. Mice homozygous for both
      mutations show more severe phenotypes than predicted by the addition of the
      individual mutant phenotypes. Both the penetrance and the expressivity of the rib
      and sternal defects are increased, suggesting synergistic interactions between
      these genes. In particular, the sternum defects are greatly exacerbated.
      Interestingly, the defects in hoxb-9 and hoxa-9/ hoxb-9 mutant mice are
      concentrated along the axial column at points of transition between vertebral
      types.

PMID- 9013930
TI  - Misexpression of nautilus induces myogenesis in cardioblasts and alters the
      pattern of somatic muscle fibers.
AB  - nautilus (nau), one member of the myogenic regulatory family of bHLH-encoding
      genes, is expressed in a subset of muscle precursors and differentiated fibers in
      the Drosophila embryo. To elucidate the role of nautilus in myogenesis, we have
      misexpressed it using the GAL4-targeted system. We find that ectopic expression
      results in lethality throughout Drosophila development. We analyzed the effects
      of embryonic expression in mesodermal tissues that include the cardioblasts of
      the dorsal vessel as well most, if not all, of the presumptive somatic muscle
      precursors. Immunohistochemical staining for muscle MHC revealed abnormalities
      that include an absence of cardial cells, coincident with the appearance of novel
      muscle fibers adjacent to the dorsal vessel. Moreover, many cardioblasts express
      increased levels of muscle-specific genes such as myosin, actin 57B, and Mlp60A,
      a protein that is restricted to the somatic, visceral, and pharyngeal muscles.
      These data suggest that the missing cardial cells have been transformed into
      cells with properties similar to those of the somatic muscles. In addition,
      ubiquitous expression of nautilus in somatic muscle cells of these embryos
      resulted in muscle pattern defects. Specifically, muscles that do not normally
      express nautilus were frequently absent, and novel fibers were observed in
      positions reminiscent of nau-expressing muscles. These data imply that nautilus
      can alter the developmental program of muscle precursors. In summary, we suggest
      that nautilus induces myogenic differentiation in vivo when ectopically expressed
      in developing cardioblasts and may affect the myogenic differentiation program of
      specific muscle fibers.

PMID- 9013931
TI  - SpHmx, a sea urchin homeobox gene expressed in embryonic pigment cells.
AB  - We describe the first complete sea urchin member of the H6 subfamily of homeobox
      genes. A cDNA encoding the complete protein was recovered from a
      Strongylocentrotus purpuratus library, and sequence comparisons demonstrate that
      this gene belongs to the same family as the Nkx-5.1, Nkx-5.2, and H6 genes of
      mammals, and the GH6 and SOHo-1 genes of chicken. In accord with current
      nomenclature this gene is named SpHmx. The gene is present in a single copy per
      haploid genome. Single-strand probe excess hybridization demonstrates that a rare
      maternal SpHmx mRNA is present in unfertilized eggs. Strong zygotic expression
      begins during the blastula stage, and the transcript is present at moderately
      high levels until late in development. Whole mount in situ hybridization reveals
      a remarkable pattern of expression: In midgastrula-stage embryos SpHmx is
      expressed throughout the archenteron, but particularly strongly in delaminating
      secondary mesenchyme cells. This more general expression resolves to a dramatic
      pigment cell-specific pattern in prism and pluteus stages. SpHmx apparently
      encodes a cell-type-specific transcription factor of embryonic pigment cells.

PMID- 9013933
TI  - Cloning and characterization of novel beta integrin subunits from a sea urchin.
AB  - Cell surface molecules that mediate adhesion in sea urchin embryos have been
      implicated in morphogenesis, and yet the molecules remain largely
      uncharacterized. Here we report evidence from PCR amplification for three novel
      beta integrin subunits that are expressed during early development of
      Strongylocentrotus purpuratus. The full cDNA sequence for one of these, betaG,
      bears a 59% similarity to Drosophila betaPS and a 58% similarity to vertebrate
      integrins. betaG closely resembles the beta1 subunit of vertebrates, particularly
      in the cytoplasmic domain where amino acids of the human beta1 subunit implicated
      in cell adhesion and signaling are conserved. The betaG subunit is detectable as
      a maternal, 7.5-kb transcript in eggs and expression peaks during gastrulation.
      Immunoblots with antiserum raised against a bacterially expressed fragment of the
      betaG subunit have bands with apparent molecular weights of about 130 kDa under
      reducing conditions and 110 kDa under nonreducing conditions.
      Immunoprecipitations suggest that betaG associates with at least two alpha
      subunits in gastrula stage embryos. In situ RNA hybridization of the betaG
      subunit indicates that all cells of the embryo express this molecule prior to
      gastrulation. In gastrulae, hybridization of the probe is highest in primary
      mesenchyme, secondary mesenchyme, the developing gut, and pigment cells. In
      immunolocalizations all cells of the blastulae express the protein at low levels
      and primary mesenchyme cells express betaG after they enter the blastocoel.
      Expression of the protein appears to be downregulated in the archenteron
      throughout gastrulation. betaG protein expression is also evident on secondary
      mesenchyme as they ingress and migrate in the blastocoel. We conclude that sea
      urchin embryos express integrins that are structurally similar to those
      characterized in other animals. Because betaG is expressed by migrating
      mesenchyme and yet is downregulated by rearranging epithelia, we suggest that
      this subunit has several functions during early development.

PMID- 9013932
TI  - Xbap, a vertebrate gene related to bagpipe, is expressed in developing
      craniofacial structures and in anterior gut muscle.
AB  - The Drosophila bagpipe (bap) gene is involved in the specification of the
      musculature of the embryonic midgut. We report the isolation and characterization
      of a Xenopus sequence, Xbap, which is closely related to bap. Xbap is also
      expressed in the developing musculature of the midgut, suggesting that this
      developmental role of bagpipe is evolutionarily conserved. However, a second,
      novel role in development is suggested by the observation that Xbap is also
      expressed in a region of the developing facial cartilage. Using a combination of
      cartilage staining and comparison to the goosecoid head expression pattern, we
      show that Xbap expression marks the precursors to the basihyobranchial,
      palatoquadrate, and possibly Meckel's cartilages. This vertebrate bagpipe
      sequence therefore is expressed in both mesodermally and neural crest-derived
      tissues.

PMID- 9013934
TI  - Mechanical signals in plant development: a new method for single cell studies.
AB  - Cell division, which is critical to plant development and morphology, requires
      the orchestration of hundreds of intracellular processes. In the end, however,
      cells must make critical decisions, based on a discrete set of mechanical signals
      such as stress, strain, and shear, to divide in such a way that they will survive
      the mechanical loads generated by turgor pressure and cell enlargement within the
      growing tissues. Here we report on a method whereby tobacco protoplasts swirled
      into a 1.5% agarose entrapment medium will survive and divide. The application of
      a controlled mechanical load to agarose blocks containing protoplasts orients the
      primary division plane of the embedded cells. Photoelastic analysis of the
      agarose entrapment medium can identify the lines of principal stress within the
      agarose, confirming the hypothesis that cells divide either parallel or
      perpendicular to the principal stress tensors. The coincidence between the
      orientation of the new division wall and the orientation of the principal stress
      tensors suggests that the perception of mechanical stress is a characteristic of
      individual plant cells. The ability of a cell to determine a shear-free
      orientation for a new partition wall may be related to the applied load through
      the deformation of the matrix material. In an isotropic matrix a uniaxial load
      will produce a rotationally symmetric strain field, which will define a shear
      free plane. Where high stress intensities combine with the loading geometry to
      produce multiaxial loads there will be no axis of rotational symmetry and hence
      no shear free plane. This suggests that two mechanisms may be orienting the
      division plane, one a mechanism that works in rotationally symmetrical fields,
      yielding divisions perpendicular to the compressive tensor, parallel to the long
      axis of the cell, and one in asymmetric fields, yielding divisions parallel to
      the short axis of the cell and the compressive tensor.

PMID- 9013935
TI  - Targeted mutation in beta1,4-galactosyltransferase leads to pituitary
      insufficiency and neonatal lethality.
AB  - Despite much attention, the function of oligosaccharide chains on glycoproteins
      and glycolipids remains largely unknown. Our understanding of oligosaccharide
      function in vivo has been limited to the use of reagents and targeted mutations
      that eliminate entire classes of oligosaccharide chains. However, most biological
      functions for oligosaccharides have been attributed to specific terminal
      sequences on these glycoside chains; yet, there have been few studies that
      examine the consequences of modifying terminal oligosaccharide structures in
      vivo. To address this issue, mice were created bearing a targeted mutation in
      beta1,4-galactosyltransferase (GalTase), an enzyme responsible for elaboration of
      many of the proposed biologically active carbohydrate epitopes. Most GalTase-null
      mice died within the first few weeks after birth and were characterized by
      stunted growth, thin skin, sparse hair, and dehydration. In addition,
      spermatogenesis was delayed, the lungs were poorly developed, and the adrenal
      cortices were poorly stratified. The few surviving adults had puffy skin
      (myxedema) and difficulty delivering pups at birth (dystocia) and failed to
      lactate (agalactosis). All of these defects are consistent with endocrine
      insufficiency, which was confirmed by markedly decreased levels of serum
      thyroxine. The polyglandular nature of the endocrine insufficiency is indicative
      of a failure of the anterior pituitary gland to stimulate the target endocrine
      organs. Previous in vitro studies have suggested that incomplete glycosylation of
      anterior pituitary hormones leads to the creation of hormone antagonists, which
      down-regulate subsequent endocrine function, producing polyglandular endocrine
      insufficiency. In GalTase-null mice, the anterior pituitary acquired a normal
      secretory phenotype during neonatal development indicative of normal glycoprotein
      hormone synthesis and secretion. However, as expected, the gland was devoid of
      GalTase activity. These results support a requirement for terminal
      oligosaccharide sequences for anterior pituitary hormone function. The fact that
      approximately 10% of the GalTase-null mice survive the neonatal period indicates
      the presence of a previously unrecognized compensatory pathway for glycoprotein
      hormone glycosylation and/or action.

PMID- 9013936
TI  - The developmental expression in the rat CNS and peripheral tissues of proteases
      PC5 and PACE4 mRNAs: comparison with other proprotein processing enzymes.
AB  - Many peptides modulating cellular growth and differentiation in development are
      first synthesized as precursors that require proteolytic processing by the
      "prohormone convertase" (PC) family of endoproteases. Using in situ
      hybridization, we have here determined that two recently identified PC members,
      PC5 and PACE4, are expressed prenatally in spatial and temporal patterns that are
      each unique and distinct from those of previously characterized PCs. PC5 mRNA is
      first detected at e9 in highly restricted regions of the neural tube, in caudal
      myotomes, and at the materno-embryonic junction of the uterus. At e10, restricted
      PC5 mRNA expression is detected in the optic and otic vesicles, the roof of
      midbrain, and trunk myotomes. By midgestation (e13-e16), PC5 mRNA expression in
      the developing nervous system has expanded to multiple regions including
      hippocampus, thalamus, hypothalamus, brain stem, and spinal cord. By
      midgestational stages, PACE4 mRNA is expressed in multiple regions of the
      developing nervous system, generally distinct from PC5, and including a uniquely
      high level of expression in the ventricular zone of the hippocampus. In several
      peripheral organ systems, including lung and gut, we observed remarkably
      complementary patterns of PC5 and PACE4 expression. In addition, PACE4
      transcripts are expressed in the heart and liver, whereas PC5 is expressed in the
      adrenal and kidney primordia. These results suggest that both PC5 and PACE4 may
      be involved in neuropeptide precursor processing in the developing nervous system
      and peripheral tissues with the general nonoverlapping expression patterns
      suggesting that PC5 and PACE4 may process distinct sets of proprotein substrates.

PMID- 9013937
TI  - Two isoforms of orthodenticle-related proteins (HpOtx) bind to the enhancer
      element of sea urchin arylsulfatase gene.
AB  - The sea urchin (Hemicentrotus pulcherrimus) arylsulfatase (HpArs) gene, expressed
      specifically in aboral ectoderm, contains a 229-bp enhancer in its first intron
      that is required for the activation of HpArs gene expression. Deletion analysis
      shows that a tandem repeat of orthodenticle-related protein (Otx) binding sites
      are responsible for the activity of this enhancer. Gel mobility shift analysis
      reveals that three types of Otx-proteins, which show different mobilities in gel
      shift assays, form complexes with the enhancer. Band I appears before hatching
      and gradually decreases by the gastrula stage. Band III appears at the blastula
      stage and Band II appears at the mesenchyme blastula stage; the levels of Band II
      and III remain constant until the gastrula stage. Two distinct types of HpOtx
      cDNA clones have been isolated from cDNA libraries of unfertilized eggs and
      gastrulae. Nucleotide sequences of the homeobox and downstream regions are well
      conserved in the two types of HpOtx cDNAs, while the region upstream from the
      homeobox has different nucleotide sequences. By genomic Southern blot analysis,
      only a single copy of HpOtx gene is detectable in the Hp genome, making it likely
      that two HpOtx isoforms are generated from the same gene. Results from Northern
      blot analysis confirm the presence of two types of HpOtx transcripts.
      Transcriptional regulation of the HpArs gene may, in part, be carried out through
      switching of Otx isoforms.

PMID- 9013938
TI  - Regulation of transcriptional activity during the first and second cell cycles in
      the preimplantation mouse embryo.
AB  - Transcription of endogenous genes in preimplantation 1- and 2-cell mouse embryos
      was determined by monitoring the incorporation of BrUTP by plasma membrane
      permeabilized embryos. Incorporation is observed starting by mid-S phase in the 1
      cell embryo and increases progressively; the amount of incorporation by the 1
      cell embryo in G2 is about 20% that of the 2-cell embryo in G2. Incorporation by
      the male pronucleus is always about four to five times greater than that of the
      female pronucleus. Nevertheless, the amount of incorporation by the female
      pronucleus present in parthogenetically activated eggs is similar to the total
      amount of incorporation in inseminated eggs, i.e., the transcriptional capacity
      of the female pronucleus is not inherently less than that of the male pronucleus.
      Inhibiting the first round of DNA replication does not prevent the initiation of
      transcription in the 1-cell embryo, but does inhibit the extent of BrUTP
      incorporation by 35%. The transcriptional machinery of the 1-cell embryo appears
      to be rate-limiting, since the total amount of BrUTP incorporation by
      parthenogenetically activated and dispermic eggs is similar to that in
      monospermic eggs; trispermic eggs incorporate BrUTP to only about 60% the level
      of monospermic eggs. A transcriptionally repressive state may start to develop in
      the 2-cell embryo, since inhibiting the second round of DNA replication results
      in an 50% increase in BrUTP incorporation. Trapoxin treatment, which induces
      histone hyperacetylation, enhances incorporation by 2-cell embryos 1.8-fold and
      suggests that histone hyperacetylation can relieve this repression.

PMID- 9013939
TI  - Identification through bioinformatics of two new macrophage proinflammatory human
      chemokines: MIP-3alpha and MIP-3beta.
AB  - An increasing number of proinflammatory peptides, known as chemokines, are
      constantly being described and characterized. Because of their proven biologic
      functions in allergy, AIDS and, in general, inflammatory processes, these
      proteins have recently gained more attention. In this study we report the
      identification through bioinformatics of two new human chemokines: MIP-3alpha and
      MIP-3beta. Both of them belong to the beta- or CC chemokine family. Expression
      studies indicate that MIP-3alpha is predominantly expressed in lymph nodes,
      appendix, PBL, fetal liver, fetal lung and several cell lines. However, MIP-3beta
      expression is restricted to lymph nodes, thymus and appendix. Interestingly
      enough, both chemokines manifested a pattern of expression strongly regulated by
      IL-10. In contrast with other CC chemokines, MIP-3beta maps to chromosome 9. Here
      we show the importance of bioinformatics to discover new molecules with possible
      therapeutic effects and regulatory functions.

PMID- 9013940
TI  - The IL-4-induced tyrosine phosphorylation of the insulin receptor substrate is
      dependent on JAK1 expression in human fibrosarcoma cells.
AB  - It has been shown that IL-4 induces the tyrosine phosphorylation of JAK1 and JAK3
      in the majority of hemopoietic cell types, and JAK2 and TYK2 in several other
      types. However, the significance of this tyrosine phosphorylation in regulating
      IL-4 signaling has not been shown. To determine whether JAKs play a role in
      activating a signal transduction pathway different from the classical JAK/STAT
      pathway, we analyzed the ability of huIL-4 to stimulate the tyrosine
      phosphorylation of one of its major cellular substrates, the insulin receptor
      substrate (IRS). Using human fibrosarcoma cell lines with mutations in JAK1,
      JAK2, and TYK2, we found that expression of functional JAK1, but not TYK2 or
      JAK2, is essential for IL-4-induced tyrosine phosphorylation of IRS. We also
      provide evidence that the IRS pathway is independent of STAT-6, showing that JAK1
      is essential for activating a STAT-independent pathway.

PMID- 9013941
TI  - CD8 alphabeta+ TCR alphabeta(intermediate) lymphocytes expressing skewed TCRVbeta
      repertoire in the liver of aged athymic nu/nu mice.
AB  - Principally, TCRalphabeta cells differentiate and mature in the thymus. However,
      evidence has accumulated to suggest that some TCRalphabeta cells develop
      extrathymically. Such cells have been identified in athymic nu/nu mice that are
      devoid of a functional thymus. They appear relatively late in ontogeny and
      randomly increase in number as a function of age. Recently, the liver has been
      suggested as a candidate site for thymus-independent development of T cells. Here
      we show that CD8alphabeta+ T cells that express TCRalphabeta at intermediate
      intensity (TCRalpha(beta)int) are preferentially localized in the liver of nu/nu
      mice. This population encompassed cells expressing lectin cell adhesion molecule
      1 and/or IL-2Rbeta and cells lacking either of these surface molecules. The
      CD8alphabeta+ TCRalpha(beta)int liver lymphocytes in nu/nu mice also differed in
      their LFA-1 expression marginally, whereas in C57BL/6 mice all CD8alphabeta+
      TCRalpha(beta)int liver lymphocytes expressed LFA-1 at low intensity. Although
      the TCRVbeta repertoire markedly differed among individual animals, the
      CD8alphabeta+ TCRalpha(beta)int liver lymphocytes in nu/nu mice preferentially
      used TCRVbeta5 and/or TCRVbeta8. These findings show that CD8alphabeta+
      TCRalpha(beta)int cells develop in the liver of nu/nu mice and that they arise
      randomly.

PMID- 9013942
TI  - Plasmin-induced proteolysis of tenascin-C: modulation by T lymphocyte-derived
      urokinase-type plasminogen activator and effect on T lymphocyte adhesion,
      activation, and cell clustering.
AB  - Proteolysis and remodeling of the extracellular matrix occur physiologically in
      processes such as tissue morphogenesis and repair and may participate in the
      regulation of complex cell functions, including proliferation and
      differentiation. While matrix degradation appears to be relevant to T lymphocyte
      migration through tissues, little is known about whether degraded matrix affects
      T lymphocyte function. We have studied the interaction between T lymphocytes and
      tenascin-C (TN-C), a matrix protein we have previously reported to inhibit T
      lymphocyte activation, in the context of plasmin-induced degradation. Here we
      report that plasmin efficiently cleaves TN-C. Peripheral blood T lymphocytes
      stimulated with phorbol ester, anti-CD28, or anti-CD3 Ab, induce, within 24 to 48
      h, a strong plasminogen-dependent proteolysis of TN-C. We demonstrate that
      stimulated T lymphocytes activate plasminogen by secreting the urokinase-type
      plasminogen activator (u-PA). Plasminogen activation by T lymphocyte-derived u-PA
      occurs efficiently in fluid phase in the absence of cells. We investigate the
      consequences of plasmin-induced proteolysis on three of the effects of TN-C in
      relation to lymphocyte functions. Plasmin proteolysis converts TN-C from a
      nonadhesive into an adhesive substrate for T lymphocytes and abolishes its
      aggregating activity on PBMC. In contrast, the inhibitory effect of TN-C on T
      lymphocyte activation remains unaffected. These observations demonstrate that
      stimulated T lymphocytes induce plasminogen-dependent proteolysis of TN-C by
      secreting u-PA and suggest that proteolysis of TN-C may represent a mechanism by
      which to regulate some of its effects on T lymphocyte functions.

PMID- 9013943
TI  - T cell adhesion to P-selectin induces tyrosine phosphorylation of pp125 focal
      adhesion kinase and other substrates.
AB  - Lymphocyte binding to endothelial surface adhesion molecules is an important
      early step in inflammation, which is mediated initially by P-selectin and E
      selectin. We tested the hypothesis that lymphocyte binding to the selectin
      adhesion molecules induces intracellular signaling by tyrosine phosphorylation.
      We used an adhesion assay, which relied on cell binding to chimeric proteins
      consisting of the extracellular domains for P-selectin and E-selectin. Tyrosine
      phosphorylation was determined using anti-phosphotyrosine Abs by confocal
      microscopy and Western blot. Binding to P-selectin induced a significant increase
      in anti-phosphotyrosine immunoreactivity. The P-selectin effect was time
      dependent with an early response after 10 min and a maximum effect at 30 min.
      Western blot showed a time-dependent phosphorylation of two distinct 68- and 125
      kDa proteins. These proteins were pp125 focal adhesion kinase (FAK) and paxillin,
      as shown by immunoprecipitation and colocalization. Phosphorylation of pp125 FAK
      was time dependent reaching a maximum after 30 min. Incubation with the tyrosine
      kinase inhibitor genistein, and, to a lesser extent, with the protein kinase C
      inhibitor staurosporine, resulted in decreased pp125 FAK phosphorylation. Our
      results are the first to demonstrate that lymphocyte binding to P-selectin
      induces tyrosine phosphorylation of distinct proteins. Thus, lymphocyte
      activation may occur already at the initial contact with surface adhesion
      molecules.

PMID- 9013945
TI  - Fc(gamma) receptor cross-linking induces peripheral blood mononuclear cell
      monocyte chemoattractant protein-1 expression: role of lymphocyte Fc(gamma)RIII.
AB  - Immune complexes activate cells by cross-linking leukocyte surface Fc(gamma)Rs.
      Diseases associated with immune complex deposition, such as rheumatoid arthritis,
      glomerulonephritis, or idiopathic pulmonary fibrosis, are characterized by
      compartmentalized monocyte infiltration. The factors that recruit monocytes to
      these compartments are not well characterized; however, monocyte chemoattractant
      protein-1 (MCP-1) has been found in areas of tissue injury. To account for these
      observations we hypothesized that PBMC Fc(gamma)R cross-linking may induce MCP-1
      synthesis, which stimulates further monocyte recruitment. To test this
      hypothesis, PBMC were incubated on increasing concentrations of immobilized human
      IgG, a stimulus for Fc(gamma)R cross-linking. Immunoreactive MCP-1 was produced
      in a dose-dependent manner (p < 0.0001). MCP-1 was specifically induced by
      Fc(gamma)R cross-linking, since immobilized F(ab')2 fragments of human IgG did
      not activate MCP-1 production. This effect was reproduced by directly cross
      linking PBMC Fc(gamma)RIII, but not by cross-linking Fc(gamma)RI or Fc(gamma)RII.
      PBMC-derived MCP-1 stimulated monocyte chemotaxis that was inhibited by a
      neutralizing anti-MCP-1 Ab. MCP-1 levels correlated with increased PBMC mRNA
      expression. Interestingly, Fc(gamma)R cross-linking with either immobilized IgG
      or anti-Fc(gamma)RIII induced more MCP-1 release from PBMC than from autologous
      monocytes (p = 0.02). Lymphocytes, the main cell type found in PBMC preparations,
      did not independently produce a significant amount of MCP-1, but when incubated
      on immobilized IgG or anti-Fc(gamma)RIII secreted a soluble factor(s) that
      induced monocyte MCP-1 production. These data suggest that cross-linking PBMC
      Fc(gamma)R induces the production of bioactive MCP-1. This occurs in part at the
      level of gene transcription and involves a cooperative interaction between
      monocytes and lymphocytes.

PMID- 9013944
TI  - G(alpha)i2-deficient mice with colitis exhibit a local increase in memory CD4+ T
      cells and proinflammatory Th1-type cytokines.
AB  - Mice with targeted deletion of the G protein G(alpha)i2 develop an inflammatory
      bowel disease closely resembling ulcerative colitis. To better define disease
      pathogenesis, the mucosal immune system in G(alpha)i2-deficient mice was studied.
      Phenotypic analysis of large intestine lamina propria lymphocytes revealed a
      large increase in memory CD4+ T cells (CD44high, CD45RBlow, CD62Llow).
      Furthermore, expression of the mucosal homing receptor integrin beta7 was
      increased on mucosal, but not systemic, CD4+ T cells. Analysis of cytokine
      production revealed a marked increase in proinflammatory Th1-type cytokines in
      inflamed colons, as compared with wild-type mice or G(alpha)i2-deficient mice
      without colitis. Thus, IFN-gamma and IL-1beta levels were increased 13-fold and
      30-fold, respectively, with more modest increases in IL-6 levels (5-fold) and TNF
      levels (2-fold). Inflamed colons of G(alpha)i2-deficient mice also demonstrated
      increased IL-12 p40 mRNA levels. No increase in IL-2, IL-4, IL-5, and IL-10 was
      seen. Large intestinal epithelial cells in G(alpha)i2-deficient mice with colitis
      were found by immunohistochemistry to express increased levels of both MHC class
      I and class II Ags. Colitis was associated with increased IgG levels (60-fold
      increase), predominantly IgG2a (135-fold increase), in large but not small
      intestinal secretions. This was shown by ELISPOT analysis to result from local
      production within the lamina propria.

PMID- 9013946
TI  - Polarization of IL-4- and IFN-gamma-producing CD4+ T cells following activation
      of naive CD4+ T cells.
AB  - Naive CD4+ T cells initially transcribe both IL-4 and IFN-gamma when stimulated
      with either the mitogen Con A or Ag in the presence of IL-4 or IL-12 and,
      therefore, appear uncommitted as to the pathway of differentiation they will
      follow. However, when stimulated either with Con A or with Ag in the presence of
      IL-4, CD4+ T cells become primed to follow the Th2 differentiation pathway, and
      we show now that by 48 h of culture in this environment these cells extinguish
      IFN-gamma gene transcription. Likewise, priming in the presence of IL-12 leads to
      the development of Th1 cells, which switch off the expression of the IL-4 gene.
      To clarify the Th1 differentiation pathway, we performed ablation studies using
      IL-4 thymidine kinase transgenic mice. When the antiviral drug ganciclovir was
      added 1 day after primary stimulation in the presence of IL-12, IFN-gamma- and IL
      4-producing cells were ablated. In contrast, when ganciclovir was added 2 days
      after primary stimulation, IL-4-producing cells, but not IFN-gamma-producing
      cells, were ablated. Thus, our studies show that by 48 h after activation, Th1 or
      Th2 cells have already become polarized to the differentiation pathway that they
      will follow. As the differentiation toward Th1 and Th2 effector cells proceeds,
      substantial amounts of IFN-gamma and IL-4 mRNA accumulate, while the mRNAs of the
      corresponding lineage (i.e., IFN-gamma in the case of Th2 cells, and IL-4 in the
      case of Th1 cells) diminish to undetectable levels. IL-4R is up-regulated during
      T cell differentiation by a mechanism mediated mainly by IL-4. The fact that IL
      12 priming does not suppress IL-4-dependent IL-4R up-regulation shows that both
      IL-4 mRNA and cytokine are produced by IL-12-primed naive CD4+ T cells during
      differentiation into Th1 cells. Naive CD4+ T cells, therefore, begin as
      uncommitted cells which express both Th1 and Th2 cytokines that rapidly
      extinguish the expression of the inappropriate cytokine as the commitment toward
      the effector lineages is made.

PMID- 9013947
TI  - TGF-beta attenuates the class II transactivator and reveals an accessory pathway
      of IFN-gamma action.
AB  - In the present report, the induction of the HLA-DRA gene in response to IFN-gamma
      is shown to be selectively attenuated by TGF-beta. Thus, the accumulation in
      response to IFN-gamma of mRNA for the DRA gene, but not for the guanylate binding
      protein-2 gene, is markedly reduced in the presence of TGF-beta. Moreover, the
      data presented show that the mechanism by which TGF-beta inhibits expression of
      DRA involves attenuation of the class II transactivator (CIITA) gene. This
      conclusion is based on the finding that induction of CIITA gene expression in
      response to IFN-gamma is completely abrogated in TGF-beta-treated cells. In
      contrast, TGF-beta did not affect IFN-gamma-induced tyrosine phosphorylation of
      Jak1, Jak2, or the signal transducer and activator of transcription-1 (Stat1).
      TGF-beta also did not inhibit the appearance of IFN-gamma-activated, Stat1 DNA
      binding activity in intact cells. Thus, the effects of TGF-beta on CIITA could
      not be explained by altered signaling through Jak-Stat1. Potential alternative
      targets for the inhibitory effects of TGF-beta were identified in renaturation
      tyrosine kinase assays, which revealed three IFN-gamma-activated protein tyrosine
      kinases that, in contrast to the Janus kinases, are sensitive to TGF-beta. These
      findings 1) indicate that inhibition of MHC class II gene expression by TGF-beta
      involves attenuation of the CIITA gene independently of effects on Janus kinases,
      2) provide direct evidence that IFN-gamma activates both Janus and non-Janus
      protein tyrosine kinases, and 3) identify an accessory pathway of IFN-gamma
      action involving tyrosine kinases that, unlike the Jak-Stat1 pathway, are
      impaired by TGF-beta.

PMID- 9013948
TI  - Reduced diversity of CTLs specific for multiple minor histocompatibility antigens
      relative to allograft rejection in vivo.
AB  - Minor histocompatibility (H) antigens stimulate in vivo rejection of allografts
      compatible for the MHC and are recognized by CTLs in short term in vitro assays.
      CTLs generated by the in vivo priming and in vitro boosting of mice with spleen
      cells incompatible for multiple minor H Ags are specific for a limited number of
      dominant Ags (peptides). We have addressed the issue of the identity of the Ags
      that stimulate rejection of solid tissue allografts vs the H Ags recognized by
      CTLs. C57BL/6 recipients reject skin grafts from BALB.B and CXB recombinant
      inbred strains with no significant differences in survival times. Primary grafts
      from these same strains prime for accelerated rejection of second-set grafts from
      all CXB strains regardless of inheritance of dominant Ags detected by CTLs.
      However, CTLs primed by these allografts and boosted in vitro do not exhibit
      ranges of reactivity with lymphoblast targets from CXB strains predicted by in
      vivo rejection, suggesting that CTLs primed by multiple Ag-incompatible skin
      grafts do not recognize all H Ags that stimulate allograft rejection. The fact
      that first- and second-set BALB.B skin grafts prime for accelerated rejection of
      11/13 congenic strains defining single BALB/c minor H Ags indicates that multiple
      H Ags stimulate allograft rejection. However, CTLs from C57BL/6 mice primed with
      BALB.B grafts and boosted with BALB.B spleen cells recognize only the H4 Ag from
      this panel of congenic strains. Limited diversity of the CTL response is
      corroborated by the recognition of three minor H peptides (including H4 as the
      most prominent) eluted from Kb molecules from a BALB.B tumor by these CTLs. These
      results indicate that CTLs recognize only a limited number of Ags operative in
      vivo and do not accurately reveal the complexity of the antigenic specificity of
      the in vivo response.

PMID- 9013949
TI  - Mouse CD38 is down-regulated on germinal center B cells and mature plasma cells.
AB  - Germinal center formation is the result of antigenic stimulation of B cells in a
      T cell-rich area. B cells cycle through the germinal centers, and a small
      percentage survive to become plasma cells or memory B cells. The transformation
      from a mature B cell into a germinal center B cell and finally into a terminally
      differentiated B cell is not well understood. Human CD38 is highly expressed on
      both germinal center B cells and plasma cells, and is useful in delineating these
      B cell subsets and in understanding the signaling events involved in the
      development of these B cells. To determine whether CD38 expression on activated
      germinal center B cells and postgerminal center B cells influences germinal
      center differentiation, we studied the expression of CD38 in the mouse. CD38 is
      expressed on follicular B cells in the Peyer's patches but is down-regulated on
      germinal center B cells located within the Peyer's patches. CD38dim/-B220+
      germinal center B cells are also found in the spleens of immunized but not
      control mice, suggesting that Ag-stimulated germinal center formation is involved
      in the production of CD38dim/-B220+ B cells. Furthermore, mature plasma cells
      isolated from in vitro LPS cultures do not express CD38, but do contain high
      levels of cytoplasmic Ig. These results are in contrast to studies in humans in
      which CD38 is not found on follicular B cells but is highly expressed on germinal
      center B cells and plasma cells.

PMID- 9013950
TI  - Molecular targets of CD45 in B cell antigen receptor signal transduction.
AB  - Expression of the phosphotyrosine phosphatase CD45 is essential for B cell Ag
      receptor (BCR)-mediated p21ras activation and calcium mobilization. To examine
      the molecular basis of this requirement, we analyzed signaling events following
      BCR ligation in CD45-deficient (CD45-) and CD45-reconstituted (CD45+) variants of
      J558Lmicrom3 cells. Ag stimulation resulted in tyrosine phosphorylation of
      cellular proteins in both cells. However, the spectrum of proteins phosphorylated
      in the CD45+ cells was qualitatively and/or quantitatively distinct from that in
      the CD45- cells. Among the protein tyrosine kinases examined, the Src family
      kinases Fyn and Blk were inducibly tyrosine phosphorylated and activated by
      receptor ligation only in CD45+ cells. While Ag-induced Btk tyrosine
      phosphorylation occurred in both cells, its activation was greatly diminished in
      the CD45- cells. Analysis of specific effector molecules revealed that tyrosine
      phosphorylation of Shc, but not rasGAP or Vav, correlated with the unique ability
      of BCR ligation to trigger p21ras activation in CD45+ cells. BCR-mediated Shc
      phosphorylation and recruitment of Grb2 depended on CD45 expression. Thus, Shc
      tyrosine phosphorylation may be the primary CD45-dependent mechanism by which Ag
      receptors are coupled to the p21ras pathway in J558Lmicrom3. In addition,
      phospholipase Cgamma1 (PLCgamma1) and PLCgamma2 were tyrosine phosphorylated upon
      Ag stimulation in CD45- cells, despite much reduced inositol trisphosphate
      production and lack of calcium mobilization. These findings suggest that CD45 may
      modulate events other than PLCgamma phosphorylation, which regulate
      phosphoinositide hydrolysis and the calcium mobilization response following BCR
      ligation.

PMID- 9013952
TI  - Down-regulation of terminal deoxynucleotidyl transferase by Ig heavy chain in B
      lineage cells.
AB  - The enzyme terminal deoxynucleotidyl transferase (TdT) adds nontemplate-derived
      nucleotides (N regions) to the junctions between recombining variable, diversity,
      and joining segments of Ig genes. The relative paucity of N regions in Ig light
      chains, together with the down-regulation of TdT transcription in pre-B cells
      (prior to light chain production), suggested that production of IgM heavy chain
      (mu) protein might negatively regulate TdT expression. In this study, we examined
      the effect of mu production on TdT gene expression in B lineage subsets from
      normal mice, from recombination-deficient mice (SCID and Rag-1-) carrying mu
      transgenes, and in transformed pro-B cell lines transfected with mu constructs.
      In normal mice, TdT is sharply down-regulated at the early pre-B stage in which
      cells have just completed productive mu rearrangement. Furthermore, the
      expression of mu transgenes in pro-B stage cells from recombination-deficient
      mice results in a similar decrease. Finally, transfection of genomic constructs
      encoding mu into pro-B cell lines results in a marked reduction of TdT
      expression. Taken together, these findings indicate that mu protein production
      results in the down-regulation of TdT. The ability of mu transgenes to alter TdT
      expression in cell lines also suggests that signaling through the pre-B receptor
      does not necessarily require interaction with an external stromal cell-derived
      ligand.

PMID- 9013951
TI  - Negative signaling in B cells causes reduced Ras activity by reducing Shc-Grb2
      interactions.
AB  - To elucidate the molecular basis for inhibition of B cell proliferation and
      differentiation by the Fc receptor for IgG (Fc(gamma)RII), we compared the
      signaling events in B cells stimulated by cross-linking surface Ig alone
      (positive signaling), or by co-cross-linking surface Ig and Fc(gamma)RII
      (negative signaling). Both modes of stimulation induced tyrosine kinase
      activation. Positive signaling induced activation of Ras, Raf-1 kinase, and
      mitogen-activated protein kinase; these events were significantly attenuated
      during negative signaling. Since Ras is activated by SOS and Vav, two known
      guanine nucleotide exchange factors, activation events associated with these
      molecules using the two different stimuli were examined. Results of these
      experiments indicated that tyrosine phosphorylation of Vav did not change upon co
      cross-linking. In contrast, the association of Shc and Grb2 was abrogated under
      negative and induced under positive signaling conditions. Concomitantly, Shc was
      observed to associate with a tyrosine-phosphorylated 145-kDa protein, previously
      identified as Src homology 2-containing inositol phosphatase, only under
      conditions of negative signaling. Based on these results, we hypothesize that
      negative signaling via the Fc(gamma)RII in B cells is at least partly the result
      of a block in Ras activation, and that SOS, but not Vav, is the major guanine
      nucleotide exchange factor in B cells for Ras activation.

PMID- 9013953
TI  - Characterization of lidocaine-specific T cells.
AB  - To investigate the cellular immune response to the drug lidocaine, we generated T
      cell lines and clones from the peripheral blood of four patients with proven
      allergy to lidocaine. The patients had contact dermatitis after topical
      application of lidocaine, and local swelling or generalized erythema exudativum
      multiforme after submucosal/subcutaneous injection of lidocaine. Two of three
      lidocaine-specific T cell lines were oligoclonal and one even became monoclonal,
      while the simultaneously analyzed immune response to tetanus toxoid was
      polyclonal. The lidocaine-specific T cell lines cross-reacted to mepivacaine, but
      not to other local anesthetics (bupivacaine, procaine, oxybuprocaine, and
      tetracaine). The majority of reactive T cells belonged to the CD4 cell lineage
      and were MHC class II restricted, but cloning also revealed some MHC class I
      restricted CD8+ clones. A total of 2 of 56 lidocaine-specific T cell clones were
      CD4-CD8- and expressed TCR-gammadelta. The majority of 13 analyzed CD4 clones
      produced a rather polarized cytokine pattern, with a dominance of Th2-like
      cytokines showing a high IL-5 production. In addition, three CD4+ and all CD8+ (n
      = 7) clones secreted high IFN-gamma and low levels of IL-5/IL-4 (Th1-like). The
      data illustrate that a drug that sensitizes via the skin elicits a heterogeneous
      T cell response. The high IL-5 production and the participation of specific
      CD4+CD8+ and even gammadelta+ T cells appear to be distinguishing features of
      this hapten-specific immune response.

PMID- 9013954
TI  - Structure and chromosomal location of the human CD6 gene: detection of five human
      CD6 isoforms.
AB  - The CD6 protein has been shown to play important roles in T cell costimulation
      and adhesion. Recently, variably spliced isoforms of CD6 mRNA have been
      identified in both human and murine T cells. Here we report on the genomic
      organization of the human CD6 gene, its chromosomal localization, and the
      characterization of novel isoforms. Human CD6 is encoded by at least 13 exons.
      The amino terminal signal sequence, extracellular region, and transmembrane
      domain are encoded by seven exons, while the cytoplasmic domain of CD6 is encoded
      by six exons. Each of the three extracellular scavenger receptor cysteine-rich
      domains is encoded by a separate exon. Fluorescence in situ hybridization studies
      and screening of a chromosome-specific YAC (yeast artificial chromosome) library
      revealed that the gene encoding CD6 is located on chromosome 11 at 11q13 in close
      proximity to the gene encoding the related molecule CD5 and within 600 kb of
      CD20. Analysis of mRNA transcripts encoding CD6 isolated from mitogen-activated
      PBMC and from B cells obtained from patients with chronic lymphocytic leukemia
      revealed the presence of at least five different CD6 transcripts. These
      transcripts arise via variable splicing of exons encoding the cytoplasmic domain
      of CD6. The existence of these isoforms suggests that signaling through CD6 could
      be regulated via alternative splicing of cytoplasmic encoding exons.

PMID- 9013955
TI  - Conformational transitions in CD4 due to complexation with HIV envelope
      glycoprotein gp120.
AB  - The binding of the surface envelope glycoprotein gp120 to its receptor, CD4, has
      been well characterized and is the primary basis for the cell tropism of HIV. In
      this study, the interaction between recombinant soluble CD4 and native membrane
      associated CD4 with gp120 is probed by the use of mAbs. Complexation of gp120
      with both forms of CD4 induces conformational epitopes that can be defined with
      specific mAbs. CG1, CG7, and CG8 are three novel mAbs that have a distinct
      preference for CD4 complexed over noncomplexed with gp120. The epitopes of these
      unique mAbs were mapped by cross-inhibition with previously characterized mAbs to
      a region encompassing the CDR2 and CDR3 loops in domain 1 of CD4. Systematic
      analysis of CG mAbs binding to CD4 and CD4/gp120 complex delineates a region in
      the D1 domain of CD4 that undergoes conformational rearrangements upon gp120
      binding to its receptor.

PMID- 9013956
TI  - The Bop gene adjacent to the mouse CD8b gene encodes distinct zinc-finger
      proteins expressed in CTLs and in muscle.
AB  - The Bop gene (for CD8b opposite) is located immediately upstream of the mouse
      CD8b gene. Expression of Bop gene transcripts was previously observed in several
      long term CTL lines and in thymus. The present studies demonstrate that
      expression of the Bop gene in lymphocytes appears to be confined to CD8-positive
      cells, and that Bop gene expression is inducible by Con A. They further show that
      a single Bop gene encodes protein products with distinct amino-terminal sequences
      that are expressed in CTLs (t-BOP) and in cardiac and skeletal muscle (skm-BOP),
      as well as what appears to be a noncoding cDNA (t-ncb) expressed only in CTLs.
      The t-BOP and t-ncb cDNAs in CTLs result from alternative splicing of a single
      primary transcript, whereas the Bop transcripts expressed in CTLs and in muscle
      appear to be transcribed from different promoters. The BOP proteins expressed in
      CTLs and muscle contain zinc finger-like motifs with homology to those of the
      ETO/MTG8 proto-oncogene and several other proteins of interest. Western blot
      analysis with a hamster anti-BOP mAb have detected the BOP protein in muscle
      cells and in COS 7 cells transfected with Bop cDNA constructs.

PMID- 9013957
TI  - An unbiased analysis of V(H)-D-J(H) sequences from B-1a, B-1b, and conventional B
      cells.
AB  - Previous studies conclude that the repertoire of B-1a (CD5+ B) cells is highly
      restricted. Studies here, which use FACS sorting and single-cell PCR methodology
      to develop an unbiased representation of the IgH repertoires of B-1a, B-1b, and
      conventional B cells from the peritoneal cavity, demonstrate that the B-1a cell
      repertoire is more diverse than previously thought. Furthermore, adult B-1a cells
      have significantly fewer noncoded nucleotide (N) insertions than conventional B
      cells. However, B-1a cells are not defined by the absence of these regions, since
      such insertions are present in two-thirds of B-1a cell transcripts. All three B
      cell populations use a wide spectrum of V(H), D, and J(H) elements and display
      considerable diversity in complementarity-determining region 3 (CDR3). However,
      characteristic differences in the repertoires of all three B cell populations
      also exist, suggesting different selective and/or developmental forces act to
      shape each repertoire.

PMID- 9013958
TI  - The 3' untranslated region of IL-1beta regulates protein production.
AB  - IL-1beta, a pro-inflammatory cytokine, has sequences in its 3' untranslated
      region (UTR) that may play a role in the post-transcriptional regulation of IL
      1beta production. To test this hypothesis, a series of chimeric reporter genes
      were developed consisting of a chloramphenicol acetyltransferase (CAT) gene the
      native 3'-UTR of which was replaced by the full-length IL-1beta 3'-UTR or various
      3'-UTR deletion mutants. Expression of these constructs under the SV40 late
      promoter in THP-1 cells showed that the full-length 3'-UTR repressed constitutive
      CAT activity to 28% of control CAT activity. Further analysis of the 3'-UTR
      localized the repressor signal to an adenosine-thymidine (AdT)-rich region. Upon
      exposure to LPS, the full-length IL-1beta 3'-UTR mediated almost a fivefold
      increase in CAT activity. The LPS response was not simply loss of AdT-mediated
      repression; when this sequence was tested alone, it did not respond to LPS. The
      LPS response effect was localized to the terminal 177 base pairs of the IL-1beta
      3'-UTR. The increase in CAT activity following LPS stimulation was associated
      with an increased CAT.IL-1beta 3'-UTR mRNA half-life, indicating at least one
      effect of the 3'-UTR on a post-transcriptional process. These studies demonstrate
      that the IL-1beta 3'-UTR is involved in the regulation of IL-1beta protein
      production, and a LPS response element may be in the IL-1beta 3'-UTR.

PMID- 9013959
TI  - Differential interaction of nuclear factors with the PRE-I enhancer element of
      the human IL-4 promoter in different T cell subsets.
AB  - The immunomodulatory cytokine IL-4 affects cells of most hemopoietic lineages. IL
      4 is secreted by activated Th2 but not Th1 cells and plays a major role in the
      immune response by modulating the differentiation of naive Th cells toward the
      Th2 phenotype. We have previously identified an enhancer element, PRE-I, that is
      essential for the function of the human IL-4 promoter. To investigate the
      mechanisms responsible for tissue-specific expression of the IL-4 gene, we
      analyzed nuclear factors binding to the PRE-I site and compared the binding
      activities of these factors to the IL-4 promoter of Th1 and Th2 cells. We show
      that PRE-I interacts with PMA- and PMA/ionomycin-inducible, cyclosporin A
      sensitive nuclear factors. Using anti-C/EBPbeta (NF-IL6), anti-C/EBPdelta (NF
      IL6beta), anti-NF-ATc, anti-NF-ATp, anti-Fos, and anti-Jun Abs we demonstrate
      that the previously identified PRE-I binding factor POS-1 is composed of
      different transcription factors in different Th cell subsets. In the IL-4
      producing Th0-like human Jurkat and mouse EL-4 cells, POS-1 (designated POS-1a)
      contains NF-IL6beta and Jun. In the mouse Th2 D10 cells and in the human Th2
      clones, POS-1 (designated POS-1b) contains NF-IL6beta, Jun, and NF-ATc/p. In
      contrast, POS-1 was not found in nuclear extracts of human Th1 clones. These
      findings suggest that PRE-I may play a role in the differential regulation of IL
      4 gene expression levels.

PMID- 9013960
TI  - Characterization of the TCRB chain repertoire in the New World monkey Callithrix
      jacchus.
AB  - Callithrix jacchus is an outbred New World primate characterized by a naturally
      occurring bone marrow chimerism, restricted polymorphism at many MHC loci, and
      unusual susceptibility to viral pathogens, adenocarcinoma, colitis, and,
      following immunization with myelin antigens, a demyelinating disease of the
      central nervous system closely resembling human multiple sclerosis. Here we
      characterize the TCRB repertoire in this species, representing the first such
      analysis in a New World monkey. Two TCRBC, 13 BJ, 2 BD, and 15 BV genes were
      identified. Overall, a high degree of similarity with human TCRBV-D-J-C gene
      sequences was observed, indicating a close phylogenetic relationship. Biased
      usage in favor of genes from the TCRBC1-BJ1 cluster was present in 77% of
      sequences, in contrast to preferential usage of BC2-BJ2 genes known to occur in
      humans and mice. Complementarity-determining region 3 averaged 10 amino acids in
      length and were diverse. Framework regions of TCRBV genes were extensively
      conserved. Phylogenetic analysis of TCRBV sequences from different species
      indicated that TCR genes are highly stable across primates. Thus, a diverse TCRB
      repertoire is generated in C. jacchus despite the limited polymorphism of class I
      MHC loci. Extensive homology to human TCR genes, natural chimerism, and
      susceptibility to inflammatory disorders are characteristics of C. jacchus that
      create a useful model system for the study of human autoimmunity.

PMID- 9013961
TI  - Preferential rearrangements of the T cell receptor-delta-deleting elements in
      human T cells.
AB  - The major part of the TCR-delta locus is flanked by the so-called TCR-delta
      deleting elements deltaRec and psi(J)alpha, which preferentially rearrange to
      each other in human thymocytes. On the basis of our combined Southern blot and
      PCR analyses, we also identified the prominent deltaRec-Jalpha58 rearrangement
      and three other preferential deltaRec rearrangements. The latter rearrangements
      concern deltaRec rearrangements to the Ddelta3, Jdelta1, and Jdelta3 gene
      segments. These deltaRec rearrangements do not delete the complete TCR-delta
      locus and are homologous to Vdelta-Jdelta rearrangements, because the majority of
      their junctional regions contain Ddelta gene segments. In contrast, the prominent
      deltaRec-psi(J)alpha and deltaRec-Jalpha58 rearrangements, representing
      approximately 68 and approximately 23% of all deltaRec rearrangements,
      respectively, are homologous to Valpha-Jalpha rearrangements, because Ddelta gene
      segments are absent in their junctional regions. Additional PCR analysis of
      Vdelta-psi(J)alpha and Vdelta-Jalpha58 coding and signal joints revealed also
      that these rearrangements resemble Valpha-Jalpha rearrangements, except for
      Vdelta2-psi(J)alpha and Vdelta2-Jalpha58 rearrangements, which resemble Vdelta
      Jdelta rearrangements. Our data show that virtually all TCR-delta-deleting
      rearrangements are Valpha-like, and the high frequency of these rearrangements in
      the human thymus suggests that most thymocytes use these rearrangements to
      further differentiate into the TCR-alphabeta lineage. Based on the very low
      frequency of deltaRec and psi(J)alpha rearrangements in 4% of the T cell acute
      lymphoblastic leukemia patients (n = 151) and 6% of the T cell lines (n = 26), we
      hypothesize that rearranged TCR-delta-deleting elements exist for only an
      extremely short period during thymocyte differentiation, probably due to rapid
      subsequent Valpha-Jalpha rearrangements.

PMID- 9013962
TI  - An anti-inflammatory role for gamma delta T lymphocytes in acquired immunity to
      Mycobacterium tuberculosis.
AB  - Although a role for gammadelta receptor-bearing T cells in the acquired immune
      response to infection with Mycobacterium tuberculosis is suggested by several
      lines of evidence, the only data indicating a possible role in specific
      protective immunity have been provided by very high dose i.v. infection models.
      In the current study, more modest low dose inocula delivered by the aerosol route
      grew identically in wild-type controls and in mutant mice in which the Cdelta
      gene of the gammadelta TCR has been disrupted by homologous recombination. This
      situation did not change if the inoculum size was increased or if an aerosol
      challenge with an M. tuberculosis strain of higher virulence was given. However,
      while the control and containment of these infections was similar, the mutant
      mice exhibited a substantial pyogenic form of the granulomatous response compared
      with the lymphocytic response seen in control animals, a finding that may well
      explain mortality in the former group if high i.v. doses are given. These data
      indicate that gammadelta T cells do not directly contribute to protection against
      tuberculosis or that they do so only when bacterial loads are very high. Instead,
      the data suggest that gammadelta T cells perhaps play an important role by
      influencing local cellular traffic, promoting the influx of lymphocytes and
      monocytes, and limiting the access of inflammatory cells that do not contribute
      to protection but may cause tissue damage.

PMID- 9013963
TI  - Mechanisms of heterosubtypic immunity to lethal influenza A virus infection in
      fully immunocompetent, T cell-depleted, beta2-microglobulin-deficient, and J
      chain-deficient mice.
AB  - Immunity that is cross-protective between different influenza A virus subtypes
      (termed heterosubtypic immunity) can be demonstrated readily in some animals but
      only rarely in humans. Induction of heterosubtypic immunity in humans by vaccines
      would provide public health benefit, perhaps offering some protection against
      pandemics or other new influenza A strains. Therefore, we studied mechanisms
      mediating heterosubtypic immunity in mice. Immunization with either A/H1N1 or
      A/H3N2 virus protected mice against mortality following heterosubtypic challenge
      while providing modest reductions in lung virus titers. No cross-protection was
      seen with distantly related type B influenza virus. Depletion of CD4+ or CD8+ T
      cells or both around the time of challenge had no significant effect on survival,
      indicating that these cells are not required at the effector stage. beta2
      microglobulin knockout mice could be protected readily against heterosubtypic
      challenge, confirming that class I-restricted T cells are not required. In beta2
      microglobulin -/- mice, depletion of CD4+ T cells partially abrogated
      heterosubtypic immunity, showing that they play a role in these mice. Passive
      transfer of Abs to naive recipients protected against subsequent challenge with
      homologous but not heterosubtypic virus. Because a role for secretory Abs has
      been suggested, we studied dependence on the J chain, which is required for
      polymeric Ig receptor-mediated IgA transport. J chain knockout mice were readily
      protected by heterosubtypic immunity, indicating that polymeric Ig receptor
      mediated transport is not required. Better understanding of heterosubtypic
      immunity should be valuable in analyzing new vaccines, including peptide and DNA
      vaccines, intended to induce broadly cross-reactive immunity.

PMID- 9013964
TI  - Enhancement of cellular and humoral immune responses to hepatitis C virus core
      protein using DNA-based vaccines augmented with cytokine-expressing plasmids.
AB  - Development of a broad based cellular and humoral immune response to hepatitis C
      virus (HCV) structural proteins may be important for irradication of infection.
      DNA-based immunization is a promising approach to generate HCV-specific immune
      responses. Previous studies of DNA-based immunizations in mice using an HCV core
      DNA expression plasmid (pHCV2-2) demonstrated an efficient CTL response against
      HCV core epitopes; however, the humoral and Th cell proliferative responses were
      found to be weak. To enhance the immunogenicity of this nonsecreted viral
      structural protein at the B and T cell level, we coimmunized mice with pHCV2-2
      and DNA expression constructs encoding for mouse IL-2, IL-4, and granulocyte
      macrophage CSF proteins. Under these experimental conditions, a seroconversion
      frequency to anti-HCV core increased from 40 to 80% in immunized mice. The CD4+
      inflammatory T cell proliferative responses as well as CD8+ CTL activity to HCV
      core protein were enhanced substantially after coimmunization with the IL-2 and
      granulocyte-macrophage CSF DNA expression constructs. In contrast, coimmunization
      with an IL-4-producing construct induced differentiation of Th cells toward a Th0
      subtype and suppressed HCV core-specific CTL activity. Taken together, these
      studies emphasize that generation of antiviral immune responses using DNA-based
      immunization may be modified by local cytokine production at the site of Ag
      presentation.

PMID- 9013965
TI  - Optimal T cell activation by melanoma cells depends on a minimal level of antigen
      transcription.
AB  - We reported previously that a large fraction of melanoma cell lines induced a
      suboptimal activation of specific CTL clones, characterized by good tumor cell
      lysis but no detectable IL-2 production. Using synthetic peptides, we
      demonstrated recently that this was due to expression of subthreshold levels of
      appropriate MHC-peptide complexes. We measure here by semiquantitative reverse
      transcription-PCR the expression of two melanoma Ag (NA17-A and Melan-A/MART-1)
      mRNAs in 13 melanoma cell lines and analyze the responses to these cell lines of
      specific HLA-A2-restricted CTL clones. In line with the idea that the density of
      MHC-antigenic peptide complexes on melanoma cells is a direct function of the
      Ag's mRNA level, we found that CTL lysis was grossly proportional to this level.
      We also established that a minimal level of transcription is required for
      melanoma cells to induce IL-2 secretion. Interestingly, all cell lines that
      expressed the Ag above this minimal level, either spontaneously or after gene
      transfection, stimulated the secretion by tumor-infiltrating lymphocyte of IL-2
      amounts proportional to Ag expression unless they exhibited a defective
      expression of intracellular adhesion molecule-1 or LFA-3 molecules or a low
      expression of the restricting HLA element. These results indicate that optimal
      activation and therefore, doubtless, full functionality of melanoma-specific CTL
      clones critically depend on the mRNA level of the Ag in tumor cells and also on a
      minimal expression of the HLA restriction element, intracellular adhesion
      molecule-1, and LFA-3. These data provide a rationale for a better selection of
      patients to be included in Ag-specific immunization protocols.

PMID- 9013966
TI  - Control of Leishmania major infection in BALB/c mice by inhibition of early
      lymphocyte entry into peripheral lymph nodes.
AB  - A single i.p. injection with the anti-CD62L (anti-L-selectin) mAb Mel-14 before
      parasite challenge protected BALB/c mice from the otherwise lethal infection with
      Leishmania major. The Mel-14 mAb treatment resulted in a significant (>90%)
      decrease in cellularity of the popliteal lymph node (PLN) with a decrease in the
      proportion of CD4+ cells and an increase of the proportion of B220+ cells.
      Furthermore, both activated cells (CD25+ and CD69+) and cells of the memory
      phenotype (CD45RBdull CD44high) were significantly enriched in PLN from Mel-14
      treated BALB/c mice. After infection with L. major, the otherwise massive
      cellular infiltration in the draining PLN was completely blocked in the Mel-14
      treated mice, and in these animals the high representation of both activated and
      memory cells in PLN remained characteristic for the first days of infection. The
      protective effect was found to be associated with a markedly increased production
      of IFN-gamma and with a decrease in IL-4 production upon restimulation of PLN and
      spleen cells with L. major Ag in vitro. The cured mice were found to be resistant
      against a secondary challenge with the parasites. These data suggest that the
      induction of a nonprotective Th2 response to L. major is associated with the
      entry of lymphocytes from the recirculating pool into the draining LN. The Mel-14
      induced changes in the lymphoid microenvironment of the draining peripheral LN
      appear to favor the development of a protective Th1 cell-mediated immune response
      against the parasite.

PMID- 9013967
TI  - Virus-specific IgD in acute viral infection of mice.
AB  - In phylogenetically diverse species with the help of T lymphocytes or soluble
      factors, viral infections induce the Ag-specific B lymphocytes to proliferate and
      terminally differentiate into IgM, IgG, IgA, IgD, or IgE Ab-secreting cells.
      Based on previous studies searching for IgD, it was inferred that serum IgD in
      the mouse is nearly undetectable, although in other species, e.g., humans, IgD is
      a measurable component of serum Ig. More recently, new information has been
      obtained indicating that IgD is secreted in minute quantities during normal B
      cell differentiation. We observed that IgD is secreted in significantly increased
      quantities in mice undergoing an acute infection with lymphocytic
      choriomeningitis virus or vesicular stomatitis virus compared with uninfected
      animals. A substantial fraction of the observed IgD was found to be virus
      specific. Using a solid-phase immunoenzymatic technique, virus-specific IgD Ab
      forming cells were detected in the spleen; their numerical increase correlated
      with the level of secreted antiviral IgD. In addition, immunohistochemical
      staining revealed IgD+ plasma cells that occurred with a similar kinetic profile
      as the virus-specific IgD Ab-forming cells. These findings provide direct
      evidence that synthesis of IgD is a physiologic event in the mouse. Its precise
      function in the immune response to pathogens, however, remains to be determined.

PMID- 9013968
TI  - Selective inhibition of human and mouse natural killer tumor recognition using
      retroviral antisense in primary natural killer cells: involvement with MHC class
      I killer cell inhibitory receptors.
AB  - The natural killer tumor recognition (NK-TR) protein has been shown to be a
      necessary component for the killing of NK-sensitive and virus-infected targets by
      the rat RNK-16 cell line. Class I-recognizing killer cell inhibitory receptors
      (KIR) have been found in the human (p58; NKAT family) and mouse (Ly-49 family).
      The principal functional characteristic of these receptors is their ability to
      block NK cell lysis by recognition of selected class I molecules on target cells.
      In the present study, we examined whether abrogation of NK-TR expression by
      retroviral infection of primary human or mouse NK cells with virus-producing
      antisense NK-TR also would demonstrate loss of non-MHC-restricted killing and
      whether the NK-TR was associated with KIR function in humans or with Ly-49 in the
      mouse. Using short term culture of fresh human or mouse NK cells, antisense NK-TR
      treated NK cells demonstrated strong selective reduction of NK cytotoxicity. NK
      TR was necessary for lytic activity even when KIR function was blocked by Ab in
      experiments involving NK3.3 lysis of HLA.cw3-expressing targets or killing of Dd
      targets by Ly-49A+ or Ly-49G2+ mouse NK cells. These studies extend our previous
      studies in rat NK cell lines to demonstrate that primary mouse and human NK cells
      require NK-TR for non-MHC-restricted lysis of tumor and virus-infected targets.
      In addition, the reversal of KIR or Ly-49 inhibition of NK cell lysis requires NK
      TR expression for cellular killing in both human and mouse.

PMID- 9013969
TI  - Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell
      mediated protective immunity against malaria.
AB  - The immunogenicity of a recombinant replication defective adenovirus expressing a
      major malaria Ag, the circumsporozoite (CS) protein (AdPyCS), was determined
      using a rodent malaria model. A single immunizing dose of this construct induced
      a large number of CS-specific CD8+ and CD4+ T cells in the spleens of these
      animals, particularly when given by the s.c. or i.m. route. A single dose of
      AdPyCS also induced high titers of Abs to Plasmodium yoelii sporozoites in mice.
      No other form of presentation of the CS protein given as a single immunizing
      dose, i.e., irradiated sporozoites, recombinant vaccinia, or influenza virus,
      etc., elicits comparably high numbers of CS-specific CD8+ T cells. The high
      concentration of CS-specific CD8+ T cells in the spleen was relatively short
      lived, decreasing to half of its original value by 4 wk and to one-third at 8 wk
      after AdPyCS inoculation. The decrease in splenic CS-specific CD4+ T cells was
      even more rapid. Most importantly, a single dose of inoculation of AdPyCS into
      mice rendered them highly resistant to sporozoite challenge, resulting in a 93%
      inhibition of liver stage development of the parasites. This protective effect
      was primarily mediated by CD8+ T cells, as shown by depletion of this T cell
      population, while depletion of the CD4+ T cell population had only a minor effect
      on anti-plasmodial activity. Moreover, the inoculation of mice with AdPyCS
      induces sterile immunity in a significant proportion of mice, preventing the
      occurrence of parasitemia.

PMID- 9013970
TI  - Proinflammatory functions of IL-2 in herpes simplex virus corneal infection.
AB  - Herpes simplex virus type 1 infection of corneas can lead to blinding
      inflammation in the corneal stroma, which is referred to clinically as herpes
      stromal keratitis. In our mouse model of this prevalent human disease, a heavy
      polymorphonuclear neutrophil (PMN) infiltration of the infected cornea leads to
      progressive tissue destruction. This inflammatory process can be abrogated by in
      vivo depletion of CD4 T lymphocytes and by neutralization of the cytokines IL-2
      and IFN-gamma. The goal of this study was to define the mechanisms by which IL-2
      mediates the corneal inflammation. Systemic neutralization of IL-2 after the
      onset of corneal disease resulted in a rapid regression of inflammation and
      complete resolution in 50% of the treated mice. The disease remission was
      associated with loss of IFN-gamma expression in the cornea, as determined by
      immunohistochemistry, and a significant reduction of IFN-gamma mRNA, as measured
      by a semiquantitative reverse transcription-PCR analysis. Within 48 h after anti
      IL-2 mAb administration, the PMN chemotactic gradient in the infected corneas was
      abolished, and those PMN that were already present in the central cornea
      exhibited clear signs of apoptotic cell death. Our results demonstrate that IL-2
      mediates corneal inflammation by 1) regulating local IFN-gamma production in an
      autocrine or a paracrine fashion, 2) establishing a PMN chemotactic gradient, and
      3) maintaining PMN viability in the cornea. These results suggest that IL-2 might
      be targeted for therapeutic intervention in this blinding disease.

PMID- 9013972
TI  - A Ca2+-dependent autoregulation of lipopolysaccharide-induced IL-8 receptor
      expression in human polymorphonuclear neutrophils.
AB  - IL-8, a potent neutrophil chemotactic agent, is known to be a key mediator in
      several inflammatory diseases. We found that 10 ng/ml of serum-activated LPS
      (Escherichia coli) efficiently up-regulated IL-8R on the surface of neutrophils
      within 30 min of LPS stimulation by 115 to 120% through de novo protein
      synthesis. After 30 min of LPS stimulation, reduction of IL-8R level was
      initiated and the normal level was restored within 2 h of LPS interaction. EDTA
      or EGTA and bestatin separately inhibited the receptor down-regulation by 98%,
      indicating the involvement of metalloprotease(s), more specifically an
      aminopeptidase in the process. Induction and subsequent reduction of IL-8 binding
      in serum-activated LPS-stimulated cells have been demonstrated in
      autoradiography. Intracellular Ca2+ level in these stimulated neutrophils was
      increased and decreased with alteration of IL-8R level. Although IL-8 binding was
      drastically reduced, the total IL-8R level, as detected by anti-IL-8R Ab measured
      by 125I-labeled anti-rabbit IgG, remained almost unaltered, indicating that
      minimal proteolysis occurred in IL-8R. Anti-IL-8R Ab and IL-8 itself could
      prevent this down-regulation significantly, suggesting that the susceptible
      epitope(s) might be in the IL-8 binding domain of the receptor. Under Ca2+
      depleted conditions, the proteolysis was inhibited, which was accelerated upon
      addition of 1 mM of CaCl2. The study demonstrates that LPS-induced up-regulation
      of IL-8R leads to amplified IL-8-mediated biologic responses of neutrophils that
      are restored to normal level by activation of a Ca2+-dependent aminopeptidase.
      This may be useful for understanding the regulation of LPS-mediated inflammatory
      responses of neutrophils during bacterial infection.

PMID- 9013971
TI  - IFN regulatory factor-1 gene transfer into an aggressive, nonimmunogenic sarcoma
      suppresses the malignant phenotype and enhances immunogenicity in syngeneic mice.
AB  - IFN-gamma has a direct antitumor effect on many tumor cell lines mediated through
      the IFN-gammaR. One effect of IFN-gamma is to induce the nuclear transcription
      factor IFN regulatory factor-1 (IRF-1), which may function as a tumor suppressor.
      In this study, mouse IRF-1 cDNA under a high constitutive expression promoter was
      transfected into the highly aggressive, nonimmunogenic MCA 101 murine sarcoma.
      Clones were obtained by G418 selection and screened for IRF-1 mRNA expression by
      reverse transcriptase-PCR (RT-PCR). High expression clones had high levels of two
      MHC class I proteins (H-2Kb and H-2Db) on the cell surface that correlated with
      increased levels of class I mRNA by RT-PCR. Furthermore, these clones also had
      increased levels of MHC class II protein (I-Ab), which correlated with increased
      levels of one subunit of class II mRNA by RT-PCR. IRF-1-expressing clones had
      markedly diminished cell growth in vitro and decreased anchorage-independent
      growth in a soft agar assay. These clones also demonstrated markedly prolonged
      tumor latency and slowed growth in syngeneic C57BL/6 mice. IRF-1 gene-transfected
      cells had shortened tumor latency and formed faster growing tumors in gamma
      irradiated immunodeficient mice compared with results in immunocompetent mice.
      Mice immunized with IRF-1-transfected cells were protected against subsequent
      challenge with IRF-1 transfected cells and also demonstrated greater tumor
      latency and slower tumor growth against subsequent challenge with untransfected
      cells compared with mice immunized with empty vector-transfected cells. These
      studies demonstrate a tumor suppressor effect of IRF-1, which acts in vivo
      through both partial reversion of the malignant phenotype and enhanced immune
      recognition and may play a role in the antitumor effects of IFN-gamma.

PMID- 9013973
TI  - Angiogenesis induced in vivo by hepatocyte growth factor is mediated by platelet
      activating factor synthesis from macrophages.
AB  - This study shows that the neoangiogenesis induced by hepatocyte growth factor
      (HGF) was associated with a local synthesis of platelet-activating factor (PAF)
      and was inhibited by the specific PAF receptor antagonist WEB 2170 in a murine
      model in which matrigel was injected s.c. as a substratum for angiogenesis. The
      synthesis of PAF was concomitant with the early migration of endothelial cells
      and infiltration of MAC-1-positive macrophages. Infiltration of lymphocytes and
      polymorphonuclear leukocytes was never observed. In vitro studies demonstrated
      that mouse peritoneal macrophages, but not two murine microvascular endothelial
      cell lines or human and bovine endothelial cells from large vessels, synthesized
      PAF after stimulation with HGF. Furthermore, macrophages expressed the transcript
      of HGF receptor encoded by the MET proto-oncogene and migrated after HGF
      challenge. The binding of HGF to its receptor was followed by the activation of
      the receptor tyrosine kinase domain and phosphorylation of the beta subunit.
      Leukocyte depletion with 5-fluorouracil and anti-MAC-1 Ab added to matrigel
      prevented the infiltration of macrophages, the synthesis of PAF and the
      angiogenesis induced by HGF. PAF extracted and purified from mice challenged with
      HGF induced a rapid angiogenic response, inhibited by WEB 2170. These results
      suggest that the angiogenic effect of HGF in vivo is mediated, at least in part,
      by PAF synthesized from macrophages infiltrating the matrigel plug.

PMID- 9013974
TI  - Inhibitory effect of growth hormone on TNF-alpha secretion and nuclear factor
      kappaB translocation in lipopolysaccharide-stimulated human monocytes.
AB  - Several studies have pointed to a link between immune and endocrine systems,
      including a regulatory function of GH on monocyte activation. The present study
      demonstrates that human THP-1 promonocytic cells, engineered by gene transfer to
      constitutively produce human growth hormone (hGH), secreted depressed amounts of
      TNF-alpha in response to challenge by LPS. The effect of GH appears to occur in
      an autocrine fashion, since the inhibitory effect on TNF-alpha secretion by
      constitutive GH production could be abolished in the presence of anti-hGH mAb.
      The GH-induced inhibitory effect was also observed using normal human monocytes
      and monocyte-derived macrophages. Inhibition of TNF-alpha production by THP-1-hGH
      transfected cells cultured in the presence of LPS is dependent on a selective
      pathway, since no inhibition of TNF-alpha production was observed when cells were
      cultured in the presence of PMA. Inhibition of TNF-alpha secretion by LPS
      stimulated THP-1-hGH cells was associated with a decrease in nuclear
      translocation of nuclear factor-kappaB. The capacity of GH to inhibit LPS-induced
      TNF-alpha production by monocytes without altering other pathways leading to TNF
      alpha production may be of potential relevance in septic shock, since GH is
      available for clinical use.

PMID- 9013975
TI  - Molecular cloning of rat C4b binding protein alpha- and beta-chains: structural
      and functional relationships among human, bovine, rabbit, mouse, and rat
      proteins.
AB  - The C4b binding protein (C4BP) functions as a regulator of the complement system
      by interacting with the activated form of the fourth complement component, C4b.
      Human C4BP also interacts with the anticoagulant protein S and the serum amyloid
      P component (SAP). It is composed of seven identical 70-kDa alpha-chains and one
      45-kDa beta-chain. The alpha-chain contains a binding site for C4b, whereas the
      beta-chain contains the protein S binding site. Recent studies have shown rabbit
      and bovine plasma to lack a C4BP-protein S complex, and the mouse beta-chain gene
      to have evolved into a pseudogene. Using a gel filtration chromatography system
      in combination with Western blotting, we detected a complex between C4BP and
      protein S in rat plasma, similar to the complex known in human plasma. Using
      purified rat C4BP and SAP we were unable to detect any complex between the two
      proteins, but rat C4BP was able to form a complex with human SAP. Rat cDNA clones
      encoding the C4BP alpha- and beta-chains were isolated from a rat liver cDNA
      library. The rat alpha-chain cDNA predicted a mature polypeptide chain of 545
      amino acid residues, whereas the beta-chain cDNA predicted a mature polypeptide
      of 243 amino acid residues. The overall amino acid sequence identities between
      the rat alpha-chain and the mouse, human, rabbit, and bovine alpha-chains were
      64, 60, 59, and 52%, respectively. The identities between the rat beta-chain and
      the human and bovine beta-chains were 68 and 57%, respectively. The rat
      represents the first non-primate species in which the C4BP-protein S interaction
      has been found to be conserved.

PMID- 9013976
TI  - Secreted chondroitin sulfate proteoglycan of human B cell lines binds to the
      complement protein C1q and inhibits complex formation of C1.
AB  - We recently characterized a species of proteochondroitin sulfate (CSPG) secreted
      by human B cell lines that closely resembles in its structure the serum-derived
      C1q inhibitor (C1qI). These proteoglycans have in common a molecular mass of
      approximately 130 to 150 kDa with a core protein of 30 kDa to which up to four
      chondroitin sulfate chains each of approximately 26 kDa are attached. Since this
      B cell-derived CSPG is a potential source for serum C1qI, we measured its
      capacity to interact with C1q in solid-phase binding and complex electrophoresis
      assays. B cell CSPG purified from culture supernatants of the two human B cell
      lines JOK-1 and U266 strongly bound to C1q. In contrast to the secreted form,
      cellular proteoglycan of the myeloma cell line U266 did not interact with C1q.
      Binding of C1q to CSPG was competitively inhibited by free glycosaminoglycans
      (GAG) in the order dextran sulfate > heparin > heparan sulfate > chondroitin-6
      sulfate (CS-C) > dermatan sulfate (CS-B) > chondroitin-4-sulfate (CS-A). B cell
      CSPG inhibited the hemolytic activity of C1q and C1. In addition, B cell CSPG
      blocked C1q receptor binding in a dose-dependent manner. The proteoglycans did
      not influence the activity of C1 complex already bound to EAC4 target cells. By
      interaction of CSPG with solid-phase-bound C1q, formation of the C1 complex upon
      the addition of C1r and C1s was impaired. Strong binding of B cell CSPG to C1q,
      its inhibition of C1q activity, and its structural similarities to the previously
      described human serum C1qI indicate that B cells produce a soluble CSPG, which
      may act as C1qI under physiologic conditions.

PMID- 9013977
TI  - Expression of IL-5 in thymocytes/T cells leads to the development of a massive
      eosinophilia, extramedullary eosinophilopoiesis, and unique histopathologies.
AB  - Transgenic mice were generated using regulatory elements from the CD3delta gene
      to drive T cell expression of IL-5. Expression of this cytokine resulted in white
      blood cell counts that expand virtually unabated (approximately 400,000
      cells/mm3). This expansion is characterized by a profound eosinophilia (>60%) and
      commensurate increases in the absolute numbers of all other white blood cell
      types. In particular, circulating B220+ B lymphocyte populations increased >30
      fold over wild-type (+/+) levels. Cell differentials and expression studies using
      a marker for eosinophil precursor cells (major basic protein gene expression)
      suggest that the peripheral eosinophilia is induced primarily through the
      establishment of extramedullary sites of eosinophilopoiesis. These mice display a
      massive peritoneal cavity cell exudate (1-2 x 10(8) cells) dominated by
      eosinophils (approximately 50%) and the infiltration of eosinophils in nearly all
      organ systems. Sudden unexplained death occurs in 70% of all transgenic animals
      by 12 mo of age. Surviving transgenic animals display severe inflammatory
      pathologies that include ulcerating skin lesions as well as lower bowel
      inflammation. These pathologies parallel clinical observations of patients with a
      profound eosinophilia and imply that IL-5 effector functions during some
      inflammatory responses may be contingent upon peripheral lymphohemopoietic
      expression.

PMID- 9013978
TI  - Expression and release of the monocyte lipopolysaccharide receptor antigen CD14
      are suppressed by glucocorticoids in vivo and in vitro.
AB  - The effect of glucocorticoid (GC) treatment on expression and release of the
      monocyte cell surface LPS receptor Ag CD14 was studied in vivo and in vitro. In
      patients with acute inflammatory diseases receiving GC pulse therapy serum
      concentrations of soluble CD14 and CD14 expression by peripheral blood monocytes
      decreased significantly. The LPS-binding capacity correlated positively with the
      amount of cell surface CD14 by human blood monocytes. In vitro, a time- and dose
      dependent effect of GC preparations on monocyte membrane and soluble CD14 by
      cultured peripheral blood monocytes was found. Incubation with 2 x 10(-8) M
      prednisolone down-regulated cell surface CD14 after 72 h, and 2 x 10(-7) M
      suppressed CD14 expression even after 24 h. Prednisolone also decreased release
      of the soluble CD14 Ag, where a 10-fold higher GC concentration was required for
      a significant suppression compared with membrane CD14 during culture. Expression
      of other monocyte membrane Ags were either unchanged (CD33, CD35), diminished
      (CD13, CD89), or increased (CD32) by GC, indicating no general down-modulation of
      cell surface Ag expression. Preincubation with glucocorticoids for 24 h
      significantly down-regulated CD14 expression during subsequent steroid-free
      culture for at least 7 days. In cultured monocytes, the LPS-induced increase of
      membrane and soluble CD14 was markedly but not completely inhibited by
      prednisolone. Therefore, GC treatment suppresses the up-regulation of the LPS
      receptor during endotoxin challenge, and likewise, the IL-1 secretion after LPS
      stimulus was significantly diminished. Taken together, the suppression of the
      monocytic cell surface and soluble endotoxin receptor CD14 by GC may contribute
      to the increased risk of infections in patients undergoing steroid therapy.

PMID- 9013979
TI  - Lymphotactin gene expression in mast cells following Fc(epsilon) receptor I
      aggregation: modulation by TGF-beta, IL-4, dexamethasone, and cyclosporin A.
AB  - Recruitment of lymphocytes is a prominent feature of allergic inflammation.
      However, the mechanisms by which lymphocytes are attracted to such sites are not
      understood. Recently, cDNAs encoding a lymphocyte-specific chemokine,
      lymphotactin (Ltn), were isolated from mouse pro-T cell and human CD8+ T cell
      libraries, leading us to hypothesize that mast cells might also produce Ltn.
      Using the reverse transcriptase-PCR and Northern blot analysis, we found that the
      Ltn gene is inducible in C1.MC/C57.1 and murine bone marrow-cultured mast cells
      (BMCMC) by Fc(epsilon)RI aggregation. Activation of a human mast cell (HMC-1) or
      basophil cell line (KU812) similarly led to transcription of Ltn. Fc(epsilon)RI
      aggregation-dependent Ltn mRNA expression was detected by 1 to 2 h, maximal at 6
      h, independent of de novo protein synthesis, and was inhibited by cyclosporin A
      and dexamethasone. Compared with macrophage inflammatory protein alpha (MIP
      1alpha), Fc(epsilon)RI-dependent Ltn and MIP-1alpha mRNA levels were up-regulated
      by IL-4, but not IFN-gamma, although higher levels of IL-4 (100 and 1000 U/ml)
      inhibited Ltn expression only; and TGF-beta preferentially enhanced Fc(epsilon)RI
      dependent Ltn mRNA levels, suggesting that Ltn and MIP-1alpha have shared and
      unique regulatory mechanisms. A rabbit polyclonal Ab against a synthetic peptide
      was developed for use in immunoblot analysis and detected a 15-kDa Ltn protein
      within mast cell pellets and in the supernatants of mast cells following
      Fc(epsilon)RI aggregation. Ltn is thus expressed in mast cells and may contribute
      to the recruitment of lymphocytes to areas of allergic inflammation.

PMID- 9013980
TI  - Chemoattractant cross-desensitization of the human neutrophil IL-8 receptor
      involves receptor internalization and differential receptor subtype regulation.
AB  - Human neutrophils undergo rapid homologous receptor desensitization following
      repeated stimulation with chemoattractants such as IL-8, C5a, and FMLP. It has
      also been demonstrated that cross-desensitization among these chemoattractant
      receptors occurs. We investigated the mechanisms underlying the cross
      desensitization of responses to IL-8 induced by pretreatment with FMLP or C5a. In
      [125I]-labeled IL-8 binding studies we found that the cross-desensitization
      induced by FMLP or C5a was associated with a subsequent reduction in IL-8 binding
      to neutrophils. There was no recovery of [125I]-labeled IL-8 binding on removal
      of the C5a or FMLP pretreatment. FACS analysis using mAbs specific for the two IL
      8R subtypes showed differential regulation of IL-8R A and IL-8R B cell surface
      expression after chemoattractant pretreatment. Homologous desensitization by IL-8
      resulted in internalization of IL-8R A and IL-8R B, but only IL-8R A was
      completely re-expressed after removal of agonist. FMLP stimulation led to a
      substantial loss of IL-8R B from the cell surface, whereas C5a stimulation
      induced only a partial loss. In both cases there was no re-expression of IL-8R B
      on removal of the chemoattractant stimulation. C5a and FMLP did not affect IL-8R
      A expression. Calcium mobilization studies using melanoma growth stimulatory
      activity and IL-8 suggest that a sustained loss of IL-8R B may play a part in
      maintaining FMLP-induced IL-8R cross-desensitization. Chemoattractant-induced
      cross-desensitization of neutrophils may be of importance in regulating
      neutrophil accumulation during the inflammatory response in vivo.

PMID- 9013981
TI  - Lipopolysaccharide-induced biphasic inositol 1,4,5-trisphosphate response and
      tyrosine phosphorylation of 140-kilodalton protein in mouse peritoneal
      macrophages.
AB  - We previously showed that a relatively high dose of LPS induced the selective
      translocation of protein kinase C-beta (PKC-beta) in LPS-responsive mouse
      macrophages. This result suggested that phosphatidylinositol-specific
      phospholipase C (PLC) might be activated in the upstream of PKC-beta. Stimulation
      of C3H/HeN mouse macrophages by LPS induced the characteristic
      phosphatidylinositol-1,4,5-trisphosphate (IP3) response, that is, a biphasic
      response consisting of a rapid increase occurring within the first 1 min, and
      another increase beginning at around 1 min after stimulation. Only the first
      response was disappeared when cells were treated with a platelet-activating
      factor receptor antagonist. LPS-inducible TNF-alpha gene activation, however, was
      not suppressed by the same antagonist, but suppressed by PKC inhibitors. LPS
      stimulated macrophage lysates showed tyrosine phosphorylation of some proteins,
      and the strongest phosphorylation was observed at molecular mass of 140 kDa. The
      phosphorylation of this protein started at 40 s after LPS stimulation and
      continued to increase. Anti-PLC-gamma2 Ab seemed to recognize the same protein as
      the tyrosine-phosphorylated 140-kDa protein. A low dose of LPS (1 ng/ml) could
      not induce the tyrosine phosphorylation of this protein. Furthermore, LPS induced
      only the first phase change, but not the second phase increase in LPS
      hyporesponsive C3H/HeJ mouse macrophages. These results indicate that the first
      phase rapid IP3 change, which is also seen in HeJ macrophages, is mediated via a
      platelet-activating factor receptor, and is not responsible for TNF-alpha
      production, while the second phase change mediated by a molecule other than CD14
      is responsible for PKC-beta translocation and TNF-alpha production. The results
      also suggest that the later IP3 change is considered to be mediated through a
      gamma2 type of phosphatidylinositol-specific PLC.

PMID- 9013982
TI  - Molecular adjuvant effects of a conformationally biased agonist of human C5a
      anaphylatoxin.
AB  - A conformationally biased decapeptide agonist of human C5a anaphylatoxin
      (YSFKPMPLaR) was used as a molecular adjuvant in stimulating Ab responses against
      peptide epitopes derived from human MUC1 glycoprotein and the human mu and kappa
      opioid receptors. C57BL6 mice were immunized with the MUC1 epitope (YKQGGFLGL);
      the C5a agonist (YSFKPMPLaR); YSFKPMPLaR and YKQGGFLGL together, but
      unconjugated; a C5a-active, MUC1 epitope construct (YKQGGFLGLYSFKPMPLaR); and a
      C5a-inactive, reversed moiety construct (YSFKPMPLaRYKQGGFLGL). High Ab titers
      specific for the MUC1 epitope were observed only in mice immunized with the C5a
      active epitope construct. Similar results were obtained in BALB/c mice immunized
      with the C5a-active, MUC1 epitope construct. Abs from the sera of the C57BL6 mice
      were predominately of the IgG2a, IgG2b, and IgM isotypes and were reactive
      against human recombinant MUC1 and MUC1 expressed by the Panc-1 M1F.15 pancreatic
      cell line. When compared with the corresponding KLH-epitope conjugates in C57BL6
      mice, the epitope-C5a agonist constructs produced titers of specific IgG Abs of
      isotypes distinct from those generated by the keyhole limpet hemocyanin-epitope
      conjugates. Rabbits immunized with a mu opioid receptor epitope-C5a agonist
      construct (GDLSDPCGNRTNLGGRDSLYSFKPMPLaR) or a kappa opioid receptor epitope-C5a
      agonist construct (FPGWAEPDSNGSEDAQLYSFKPMPLaR) generated high titer, epitope
      specific Ab responses. Ab titers generated in response to the opioid epitope-C5a
      agonist constructs were comparable to those generated by the opioid KLH-epitope
      conjugates. The results of this study are discussed in terms of possible
      mechanisms by which the conformationally biased C5a agonist serves as a molecular
      adjuvant.

PMID- 9013983
TI  - On the essential involvement of neutrophils in the immunopathologic disease:
      herpetic stromal keratitis.
AB  - Corneal infection with herpes simplex virus-1 in immunocompetent mice induces an
      immunopathologic response termed herpetic stromal keratitis (HSK). The earliest
      sign of disease is neutrophil infiltration, which lasts for 48 to 72 h and then
      disappears. However, a secondary neutrophil infiltration, this time more massive,
      occurs, beginning 8 to 9 days postinfection, a time in which HSK becomes
      clinically evident. The role of neutrophils in HSK expression was investigated by
      eliminating such cells using a specific mAb (RB6-8C5). In neutrophil-depleted
      immunocompetent mice, virus replicated more abundantly, but no effects on HSK
      expression were observed, possibly because sustained neutropenia could not be
      maintained. However, using a severe combined immunodeficient mouse model, in
      which HSK does not occur unless given adoptive transfer of CD4+ T cells, the
      effects of neutrophil depletion were more pronounced. There were significantly
      less incidence and severity of HSK in CD4+ T cell-reconstituted severe combined
      immunodeficient mice that were depleted of neutrophils as compared with controls.
      Neutrophil-depleted mice displayed moderate to severe periocular skin lesions,
      progressively became cachetic, and developed signs of encephalitis. Virus was
      recovered at higher titers and for longer periods from eyes of neutrophil
      depleted animals. Brain virus titers were also significantly higher on day 12
      postinfection as compared with control animals. These results suggest that herpes
      simplex virus infection of the cornea rapidly invokes recruitment of neutrophils
      that may aid in viral clearance, and that neutrophils directly or indirectly
      serve as agonists in perpetuating a CD4+ T cell-mediated inflammatory reaction.

PMID- 9013984
TI  - Regulation of lung fibroblast alpha-smooth muscle actin expression, contractile
      phenotype, and apoptosis by IL-1beta.
AB  - IL-1 is important in regulating lung inflammation and potentially fibrosis as
      well. To clarify the role of this cytokine vis-a-vis changes in lung fibroblast
      phenotype in pulmonary fibrosis, the effects of IL-1beta on isolated lung
      fibroblasts were examined. Rat lung fibroblasts were treated with increasing
      doses of IL-1beta and examined for effects on cell number, alpha-smooth muscle
      actin expression, apoptosis, nitric oxide (NO) production, and contractility in
      collagen gels. The results show that IL-1beta caused dose-dependent down
      regulation of alpha-smooth muscle actin protein and mRNA expression. The kinetics
      of mRNA inhibition was rapid and preceded the effects on protein expression. This
      IL-1beta-induced decrease in actin expression was associated with inhibition of
      contractility evaluated using fibroblast-populated collagen gels. Since IL-1beta
      inhibition of actin expression was accompanied by reduction in cell number, the
      effect on apoptosis was examined. Significant increase in the number of apoptotic
      nuclei and DNA fragmentation was observed upon IL-1beta treatment, with a dose
      response curve that mirrored that for the decline in actin-positive cells. More
      than one-half of the apoptotic cells were actin positive at high IL-1beta doses,
      suggesting that the actin-expressing cells may be more susceptible to IL-1beta
      induced apoptosis. IL-1beta also induced NO production in these cells, which was
      inhibited by NG-monomethyl-L-arginine. Similarly, IL-1beta-induced apoptosis and
      inhibition of actin expression were inhibited by this arginine analogue. Hence,
      induction of apoptosis by IL-1beta via NO production may be an important
      mechanism for regulating lung fibroblast alpha-smooth muscle actin expression,
      and consequently its contractile phenotype as well.

PMID- 9013985
TI  - Linomide administration to mice attenuates the induction of nitric oxide synthase
      elicited by lipopolysaccharide-activated macrophages and prevents nephritis in
      MRL/Mp-lpr/lpr mice.
AB  - Nitric oxide is involved as a messenger molecule in a large number of physiologic
      and pathologic responses. Local generation of high nitric oxide output through
      the expression of the calcium-independent, cytokine-inducible form of nitric
      oxide synthase (iNOS) can result in either protective or damaging effects. The
      development of drugs that specifically suppress iNOS expression or inhibit its
      activity may therefore provide an excellent therapeutic tool for treatment of a
      diverse set of dysfunctions, including asthma, inflammatory processes, and
      autoimmune disease. We show compelling evidence that linomide, an immunomodulator
      known to ameliorate autoimmune diseases, prevents accumulation in the macrophages
      of mRNA encoding iNOS in mice injected with LPS. This effect is partially
      mediated by the blocking of TNF-alpha and IL-beta production by activated
      macrophages. Here, we also present evidence that kidneys from MRL/Mp-lpr/lpr mice
      express high iNOS levels when the mice develop glomerulonephritis. The
      administration of linomide to MRL/Mp-lpr/lpr mice significantly decreases iNOS
      mRNA levels and prevents the development of glomerulonephritis, extending the
      half-life of mice of this strain. This linomide effect is compatible with its
      role in preventing the development of autoimmune disease and extends its possible
      use to other pathologic manifestations associated with iNOS expression, such as
      the systemic lupus erythematosus-associated glomerulonephritis present in MRL/Mp
      lpr/lpr mice.

PMID- 9013986
TI  - Targeted expression of the neuropeptide calcitonin gene-related peptide to beta
      cells prevents diabetes in NOD mice.
AB  - To investigate whether the immunosuppressive neuropeptide calcitonin gene-related
      peptide (CGRP) was a potential candidate for tissue-specific gene therapy, we
      engineered nonobese diabetic (NOD) mice to produce CGRP in beta cells by placing
      the modified calcitonin gene under the control of the rat insulin promoter. CGRP
      inhibits CD4 T cell production of the cytokines that have been implicated in the
      pathogeny of type I diabetes. Three transgene-positive mouse lines were obtained,
      two of which expressed immunoreactive CGRP in beta cells (NOD-CGRP mice).
      Isolated islets from one of these two transgene-positive founders produced active
      CGRP, whereas islets from transgene-negative littermates did not. The production
      of CGRP by beta cells prevented insulin-dependent diabetes mellitus in male and
      reduced its incidence by 63% in female mice. This prevention was due to a local
      immunosuppressive effect of CGRP as no difference was detected between NOD-CGRP
      and NOD littermate lymph node, spleen, and thymus cells by either FACS analysis
      or proliferative response to stimulation by Ag, alloantigen or anti-CD3. These
      data suggest that CGRP is a potential therapeutic molecule to prevent or treat
      diabetes and possibly other diseases and conditions in which immune cells are
      involved. These data also suggest that endogenous CGRP concentrated in sensory
      nerve endings may regulate locally the immune response, further strengthening the
      importance of the functional neuroimmune link.

PMID- 9013987
TI  - Age-dependent intestinal lymphoproliferative disorder due to stem cell factor
      receptor deficiency: parameters in small and large intestine.
AB  - Signaling through c-Kit/stem cell factor (SCF) is crucial for normal development
      of erythroid and myeloid hematopoietic precursors and of melanocytes and germ
      cells. While peripheral lymphoid populations of W/Wv and SI/SId mice appear
      normal, we demonstrated that the intraepithelial lymphocyte (IEL) populations of
      small (SI) and large (LI) intestine were significantly affected. IEL populations
      of young W/Wv animals were indistinguishable from those of their control
      littermates, but an age-dependent decrease in SI and LI TCRgamma delta IEL
      occurred in c-Kit mutant mice. In SI, but not in LI, this diminution was
      accompanied by gross expansion of TCRalpha beta IEL that resulted in
      significantly increased IEL:epithelial cell ratios in c-Kit mutant mice.
      Bromodeoxyuridine labeling studies revealed that the increase in cell numbers was
      due to lymphoproliferation that occurred in situ. Interestingly, TCRgamma delta
      IEL expressed cell surface c-Kit, while the expanding population of TCRalpha beta
      IEL did not. Analysis of radiation bone marrow chimeras demonstrated that the
      dysregulation required either disruption of stromal cell SCF or IEL c-Kit and
      showed that the effect on IEL or their precursors was not due to other changes in
      the intestinal microenvironment. Lamina propria T cell populations in these mice
      were unaffected, reinforcing the idea that the developmental requirements of
      these gut-resident lymphocyte populations are distinct. Overall, the results
      demonstrated that the development of intestinal TCRgamma delta IEL, regardless of
      location, shares common requirements for SCF, while SI and LI TCRalpha beta IEL
      may develop along distinct pathways. Possible mechanisms for the loss of
      proliferative regulation in gut T cells in c-Kit/SCF deficiency are discussed.

PMID- 9013988
TI  - Local-clonal expansion of infiltrating T lymphocytes in chronic encephalitis of
      Rasmussen.
AB  - Rasmussen's syndrome is a progressive and intractable form of epilepsy
      characterized pathologically by focal brain inflammation with large numbers of
      infiltrating T lymphocytes. To better understand the nature of the T cell
      response in this disease, we analyzed TCR expression in the brain lesions using
      PCR for quantitative assessment of TCRBV gene transcripts, together with size and
      sequence analysis of the third complementarity-determining region (CDR3) of the
      dominant TCR rearrangements. Restricted (oligoclonal) BV family usage was not
      observed, as all of the 22 BV PCR products were usually detected at levels
      exceeding the background. However, significant individual biases in the
      frequencies of different TCR families was evident. The distinct pattern of BV
      expression by infiltrating lymphocytes detected in the original PCR screening
      suggested a specific immune response. The primary structure of the rearranged
      CDR3 sequences for the BV family expressed at highest level in each sample was
      studied by size and sequence analysis. The data showed that predominant TCR BV
      families expressed in diseased brain tissue displayed limited size heterogeneity
      and extensive repetition of in-frame CDR3 nucleotide motifs. These findings
      demonstrate that the local immune response in Rasmussen's syndrome includes
      restricted T cell populations that have likely expanded from a few precursor T
      cells responding to discrete antigenic epitopes.

PMID- 9013989
TI  - Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo
      treatment of atopic patients with anti-IgE antibody.
AB  - Treatment of allergic disease by decreasing circulating IgE with anti-IgE Abs is
      currently under clinical study. Based on previous unrelated studies, it appeared
      likely that Fc(epsilon)RI expression on basophils and mast cells might also be
      regulated by levels of circulating IgE Ab. Therefore, the expression of IgE and
      Fc(epsilon)RI on human basophils was examined in 15 subjects receiving humanized
      anti-IgE mAb intravenously. Treatment with the anti-IgE mAb decreased free IgE
      levels to 1% of pretreatment levels and also resulted in a marked down-regulation
      of Fc(epsilon)RI on basophils. Median pretreatment densities of Fc(epsilon)RI
      were approximately 220,000 receptors per basophil and after 3 mo of treatment,
      the densities had decreased to a median of 8,300 receptors per basophil. Flow
      cytometric studies, conducted in parallel, showed similar results and also showed
      in a subset of 3 donors that receptors decreased with a t1/2 of approximately 3
      days. The responsiveness of the cells to IgE-mediated stimulation using anti-IgE
      Ab was marginally decreased (approximately 40%) while the response of the same
      cells to stimulation with dust mite Ag, Dermatophagoides farinae, was reduced by
      approximately 90%. One possible explanation for these results is that
      Fc(epsilon)RI density is directly or indirectly regulated by plasma-free IgE
      levels.

PMID- 9013990
TI  - In patients with rheumatoid arthritis IgG binding to denatured collagen type II
      is in part mediated by IgG-fibronectin complexes.
AB  - The presence of autoantibodies to native and denatured collagen type II has been
      reported in some patients with rheumatoid arthritis (RA). This study examined the
      molecular nature of IgG binding to native and denatured collagen type II. The
      binding of IgG to native and denatured collagen was detected with an ELISA. Serum
      proteins were separated by size with gel filtration. Gel-filtered fractions were
      further characterized by binding to staphylococcal protein A. Among plasmas or
      serums from 60 patients with RA, 12 patients had IgG binding to native collagen
      type II and 12 had IgG binding to denatured collagen type II. Decomplementing
      normal serums by heating to 56 degrees C for 30 min markedly increased IgG
      binding to denatured collagen type II, but not to native collagen. This binding
      was shown to result from a complex formed between IgG and fibronectin. Nine
      unheated RA serums were separated by gel filtration. The IgG binding to native
      collagen was limited to monomeric IgG, but in these serums 65.6 +/- 22.0% of the
      IgG binding to denatured collagen type II was in the excluded protein fractions.
      The binding of IgG to denatured collagen type II in the excluded fractions was
      inhibited by fibronectin and did not bind to staphylococcal protein A. In
      patients with RA, the IgG binding to native collagen type II represents true
      autoantibodies. In contrast, in these patients the majority of IgG binding to
      denatured collagen type II is caused by macromolecular complexes formed between
      fibronectin and IgG or between fibronectin and IgG-containing immune complexes.

PMID- 9013991
TI  - Protection against autoimmune diabetes in mixed bone marrow chimeras: mechanisms
      involved.
AB  - After bone marrow transplantation, complete nonobese diabetic (NOD) into (NOD x
      C57Bl/10)F1 chimeras developed insulitis in 100% (7/7) and diabetes in 58% (7/12)
      of cases. In contrast, when mixed chimerism was induced, a near complete
      protection against insulitis (3/23, p < 0.0001 vs complete chimeras) and diabetes
      (0/25, p < 0.001 vs complete chimeras) was achieved even in chimeras with as few
      as 5% F1 cells. In cotransfer experiments, splenocytes from mixed chimeras failed
      to prevent diabetes, thus overruling a role for suppressor cells in protection.
      Whereas splenocytes from complete chimeras transferred diabetes into young
      irradiated NOD mice in all cases, NOD splenocytes from mixed chimeras only rarely
      transferred diabetes (3/16, p < 0.01 vs complete chimeras), suggesting that the
      latter cells had developed tolerance toward beta cells. To achieve this
      tolerance, the presence of an F1 thymus was not needed. Indeed, whereas
      splenocytes isolated from complete chimeras were diabetogenic when transferred
      into neonatally thymectomized irradiated NOD recipients (3/4), they failed to
      induce diabetes when transferred into neonatally thymectomized irradiated F1
      recipients in case again a state of mixed chimerism was induced (0/4, p < 0.001
      vs NOD recipients). Finally, a role for non-MHC Ags was demonstrated by
      experiments in F1 mice crossed between NOD and C57Bl/6, a strain congenic to
      C57Bl/10. Here protection against disease was only seen in the presence of high
      levels of F1 cells (>25%). In conclusion, mixed bone marrow chimerism can induce
      self-tolerance in autoimmunity prone NOD immune cells. This can be achieved
      extrathymically but may depend on non-MHC Ags and the level of chimerism.

PMID- 9013992
TI  - Evidence for the role of an altered redox state in hyporesponsiveness of synovial
      T cells in rheumatoid arthritis.
AB  - In rheumatoid arthritis (RA), T cells isolated from the synovial fluid (SF) show
      impaired responses to mitogenic stimulation compared with T cells from the
      peripheral blood (PB). Here it is reported that hyporesponsiveness of SF T cells
      correlated with a significant decrease in the levels of the intracellular redox
      regulating agent glutathione (GSH). GSH was decreased in both CD4+ (p = 0.0022)
      and CD8+ (p = 0.0010) SF T cell subsets compared with PB CD4+ and CD8+ T cells in
      RA patients. Levels of thioredoxin (TRX), another key redox mediator, previously
      found to be secreted under conditions of oxidative stress, were found to be
      significantly increased in SF compared with plasma samples of RA patients (p =
      0.005). Increased levels of TRX in the SF of inflamed joints was found to be
      associated with RA when compared with other arthritides (p = 0.007). Restoration
      of GSH levels in SF T cells with N-acetyl-L-cysteine (NAC), enhanced mitogenic
      induced proliferative responses and IL-2 production. Collectively, these data
      impute an important role to an altered redox state in the hyporesponsiveness of
      joint T cells in patients with RA.

PMID- 9013993
TI  - Roles of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice.
AB  - Development of either Th1 or Th2 cell subsets has profound immunologic
      consequences, either pathogenic or protective, in several autoimmune diseases.
      However, it remains unclear which subset of Th cells plays a more critical role
      in lupus. In this study, we examined IL-4 and IL-12, which play decisive roles in
      the development of Th2 and Th1, respectively, in the IgG autoantibody production
      and development of lupus nephritis in NZB/W (B/W) F1 mice. Transfer of either IL
      4- or IL-12-stimulated splenocytes from 5-mo-old B/W F1 mice into B/W F1 mice of
      the same age enhanced the production of IgG anti-dsDNA Ab. Consistently,
      administration of mAb against either IL-4 or IL-12 before the onset of lupus
      could inhibit the production of IgG anti-dsDNA Ab. However, only anti-IL-4 mAb
      was effective in preventing the onset of lupus nephritis. This discrepancy
      appeared to be explained by the differential effect on the production of IgG3
      type autoantibody and TNF production. Interestingly, when combined, anti-IL-12
      mAb abrogated the beneficial effect of anti-IL-4 mAb. These results indicate that
      both Th2 and Th1 contribute to the IgG autoantibody production, and IL-4 and IL
      12 play key roles in the complexity of cytokine regulation in the pathogenesis of
      autoimmunity in lupus, but the former is more critical.

PMID- 9013994
TI  - The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic
      hepatitis C.
AB  - Cellular immune responses, particularly those mediated by CD8+ CTL, may be
      important in the pathogenesis and control of hepatitis C virus (HCV) infection.
      To define the role of HCV-specific CTL in chronic hepatitis C, HCV-specific CTL
      activity in liver and peripheral blood was assessed in 35 patients with chronic
      HCV infection and 5 non-HCV controls. HCV-specific CTL activity of expanded CD8+
      cells was evaluated against autologous lymphoblastoid cells transduced with
      recombinant vaccinia virus vectors expressing HCV genotype 1a Ags. CTL activity
      was detected in unprimed bulk-expanded CD8+ cells derived from the liver in 16 of
      the 35 patients, but not in peripheral circulation. Three patients infected with
      non-type 1 HCV were found to have HCV-specific CTL activity against HCV type 1a
      epitopes, all directed toward HCV core region. Compared with patients without
      detectable HCV-specific CTL activity based on our assay, those exhibiting CTL
      activity had lower levels of viremia (p < 0.01 for both branched DNA version 1.0
      and 2.0 assays) and more active disease, as reflected by a higher histologic
      activity index (p = 0.006) and serum alanine aminotransferase levels (p = 0.03).
      It is concluded that 1) with nonspecific stimulation, HCV-specific CTL activity
      is found more commonly in the liver than in peripheral circulation, suggesting a
      tissue-specific localization with HCV-specific CTL and/or its precursors; 2)
      cross-genotype CTL activity exists, especially toward HCV core, which is
      relatively conserved across genotypes; and 3) patients with intrahepatic HCV
      specific CTL activity had lower levels of viremia and more active liver disease.

PMID- 9013995
TI  - Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic
      lymphocytic leukemia.
AB  - The role of T cells in chronic lymphocytic leukemia (CLL) has not been
      extensively investigated, since the most prominent cellular abnormality in CLL
      involves the clonal expansion of B cells. In this study we have undertaken a
      comprehensive analysis of the CD4+ and CD8+ T cell repertoire in a population of
      CLL patients (n = 19) and age-matched controls (n = 22). The TCR repertoire
      analysis was performed using a multiplex PCR assay for CDR3 length, an approach
      that allows for the detection of underlying oligoclonality in complex T cell
      populations. We established that oligoclonality was substantially more frequent
      in both the CD4+ and CD8+ T cell populations of CLL patients than in the age
      matched controls (p < 0.001). Using three-color FACS analysis with a panel of
      TCRV segment-specific mAbs, we also established that oligoclonal expansions are
      predominantly found in the CD57+ subset of both the CD4+ and CD8+ T cell
      populations. The frequency of the CD57 marker on CD4+ T cells was increased in
      the setting of CLL (% CD57 = 14.8 +/- 13.0%) compared with that in normal
      controls (% CD57 = 3.3 +/- 3.0%; p < 0.001). An elevated frequency of CD4+CD57+ T
      cells was correlated with more advanced disease. Similarly, the most extreme
      oligoclonal expansions of CD4+CD57+ T cells occurred in CLL patients who had
      progressed beyond Rai stage 0. These data document profound alterations in the T
      cell repertoire of CLL patients and point to a role for clonal T cell populations
      in the pathogenesis of this disease.

PMID- 9013996
TI  - Down-regulation of surface receptors for TNF and IL-1 on circulating monocytes
      and granulocytes during human endotoxemia: effect of neutralization of endotoxin
      induced TNF activity by infusion of a recombinant dimeric TNF receptor.
AB  - Leukocytes rapidly lose their surface receptors for TNF and IL-1 upon exposure to
      various stimuli in vitro. We sought to determine by FACS analysis changes in the
      expression of TNF receptors (TNFR) and type II IL-1R on circulating monocytes and
      granulocytes during endotoxemia in vivo, and the role of endogenous TNF in these
      changes. Twelve healthy subjects received an i.v. injection with LPS (2 ng/kg),
      directly preceded by a 30-min infusion of either a recombinant human dimeric TNFR
      type II-IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) or vehicle (n = 6). LPS
      administration was associated with decreases in the expression of types I and II
      TNFR and type II IL-1R on both monocytes and granulocytes. Treatment with TNFR:Fc
      completely neutralized LPS-induced TNF activity (p < 0.0001 vs LPS only),
      modestly blunted the decrease in monocyte TNFR (p < 0.05), but did not influence
      reduced expression of granulocyte TNFR or monocyte/granulocyte type II IL-1R. In
      separate experiments, rTNF added to whole blood reduced cellular type I and type
      II TNFR expression by an effect on the type I TNFR; TNF did not (monocytes)
      decrease or only marginally (granulocytes) decreased type II IL-1R expression.
      LPS induces down-modulation of monocyte and granulocyte receptors for TNF and IL
      1 in humans in vivo. TNF is involved in reduced monocyte TNFR expression during
      endotoxemia.

PMID- 9013997
TI  - Twinning rate in a southeastern Brazilian population.
AB  - The twinning incidence from 1984 to 1993 was investigated in Campinas, State of
      Sao Paulo, Brazil and the analyzed data were combined with previous series from
      the same population. This study has shown that the mean annual incidences and the
      standard deviations for DZ, MZ and DZ plus MZ twins for the period of 1984 to
      1993 are estimated respectively as 4.7 +/- 0.92, 4.1 +/- 1.11, and 8.8 +/- 0.87
      per 1,000. In the same period the mean annual incidence of triplets was 0.15 +/-
      0.16. It was also shown that the incidence of DZ twins is steadily decreasing
      since 1925, while the incidence of MZ pairs, after a period of decline is
      increasing since the sixties, due perhaps to the widespread use of oral
      contraceptives. Concerning the twinning rate as a whole, it has been shown that
      its declining trend has disappeared over the last few years.

PMID- 9013998
TI  - Cognitive development and behaviour in very low birthweight twins at four years.
AB  - This study included two groups of 37 children, one of twins and the other
      singletons at 4 years of age. All subjects has birthweights under 1500 grams and
      individuals in the groups were matched for birth date, gender and birthweight.
      Except when parental socio-economic status was taken into account, no significant
      differences between twins and singletons were observed on any of the results of
      The Stanford-Binet Intelligence Scale, nor were there any when the twins and
      singletons were divided into groups with birthweights < 1000 grams and 1000 to
      1499 grams. When cognitive scores were analysed in relation to socio-economic
      status, there were significant differences in the whole population between
      subjects in the high and low socioeconomic status groups, with higher mean scores
      for the former. Comparison of the twins and singletons with parents in the lower
      socio-economic status group did not produce any significant differences but in
      the case of the upper socio-economic status group the singletons scored
      significantly better than the twins in Quantitative Reasoning and on the
      Composite Score. No significant differences were demonstrated in the clinical
      assessment of speech, language or behaviour. So far as general life
      considerations and health were concerned only one significant difference was
      found and this was for the number of siblings born subsequently, with more born
      in the singleton families. This study did not provide support for the view that
      singletons and twins differ significantly in the areas considered.

PMID- 9013999
TI  - Reducing fetal deaths in multiple births: optimal birthweights and gestational
      ages for infants of twin and triplet births.
AB  - The objective of this study was to determine the birthweight and gestational age
      associated with the lowest fetal mortality for twins and triplets. The study
      design was a population-based analysis of all live births and fetal deaths in the
      US between 1983-88. Fetal mortality was compared by categories of birthweight and
      gestational age, for twins and triplets versus singletons, and within each
      plurality by the lowest rate compared to all other rates as relative risks +/-
      95% Cls. The overall versus lowest fetal death rate per 1,000 conceptions for
      singletons was 4.3 versus 0.9 at 3700-4000 g and 40-41 weeks; for twins, 15.5
      versus 3.3 at 2500-2800 g and 36-37 weeks; and for triplets, 21.0 versus 5.2 at
      1900-2200 g at 34-35 weeks. Beyond these plurality-specific lowest ranges, the
      risk of fetal death increased, more for twins than singletons, and most for
      triplets. To conclude, fetal death rates can be reduced by 75-80% with attainment
      of birthweight and gestational age within a plurality-specific ideal range.

PMID- 9014000
TI  - The "equal environments assumption" in MZ-DZ twin comparisons: an untenable
      premise of psychiatric genetics?
AB  - The comparison of MZ-DZ twins in behavioral genetics has produced what seems like
      irrefutable evidence for the heritability of many psychiatric disorders. But such
      research depends on the validity of the EEA--the "equal environments assumption"-
      as an underlying premise. In this paper, several empirical studies which support
      the EEA are critically reviewed in terms of methodology and the way data has been
      processed in a mathematical model called "path analysis". It turns out that
      studies investigating the EEA appear to be largely inadequate in terms of
      technique, as well as biased in the inferences drawn. Further, the "heritability"
      estimate--often taken to mean the influence of trait-specific genes--is merely a
      statistical abstraction derived from a matrix of correlations; this estimate
      encompasses many buried environmental effects so that "heritability" does not
      correspond to any underlying DNA structure. In conclusion, many MZ-DZ pedigree
      studies have dubious scientific value, given the non-viable premise of the EEA,
      as well as the misleading operational definition of what has been called
      "heritability".

PMID- 9014001
TI  - Ethnic variation of twinning rates in Malawi.
AB  - Malawi is a country in South-East Africa with a population of approximately 10
      million, over 95% of whom are negro of Bantu origin. The country is divided into
      24 administrative districts, each of which provides details of births which are
      compiled centrally at the Ministry of Health. Using data reported annually by
      health facilities from 1987-1990, most districts had twinning rates in the range
      16 to 24 per 1000 maternities, figures consistent with those of other negro
      populations in Africa. Two adjoining districts (Rumphi and Mzimba) had rates
      which were considerably higher, almost 30 per 1000. Although ethnic origin is not
      recorded in the latest Malawi census, language spoken in the home, which was last
      recorded in 1966, can be used as a proxy. Rumphi and Mzimba are the only
      districts with an overwhelming majority of Tumbuka speaking population. These
      people, who are of both Tumbuka and Ngoni ethnic origin, therefore have an
      unusually high twinning rate (29.57 per 1000 maternities). The rate for the main
      ethnic group in Malawi, the Chewa people, was 21.21 per 1000. The district of
      Thyolo, with a mixed ethnic population, had by far the lowest rate (13.75 per
      1000).

PMID- 9014002
TI  - Management and outcomes of 65 quadruplet pregnancies: sixteen years' experience
      in France.
AB  - OBJECTIVE: Data on the prognosis and management of multifetal pregnancies are of
      vital importance, particularly when the option of selective termination is
      considered. The present study details the obstetric management, neonatal outcome,
      and follow-up data of 65 quadruplet pregnancies in France. METHODS: To conduct
      the study, a questionnaire was sent to families registered with the National
      Association Helping Parents of Multiple Births (Association National d'Entraide
      des Parents de Naissance Multiples, A.N.E.P.N.M.). RESULTS: Of 116 questionnaires
      sent to families of quadruplets born between 1972 and 1988, 65 were received. Of
      these pregnancies, 58 were obtained with ovulation induction agents, 2 with IVF
      (in vitro fertilization) and GIFT (gamete intrafallopian transfer) and 5 were
      spontaneous. Diagnosis was made prior to 13 weeks gestation in 87.2% of cases.
      Most mothers were hospitalized prior to delivery--mean duration of 47 days. The
      mean gestational age at delivery was 31.2 +/- 3 weeks with a prematurity rate of
      97%. Cesarean sections were performed in 51 cases and vaginal deliveries in 14.
      Neonatal and perinatal mortality rates were 68 and 104 per 1000, respectively.
      Birthweights of quadruplets ranged from 760 to 2455 g with a mean of 1615 g.
      CONCLUSION: Management of quadruplet pregnancies in France consists of early
      diagnosis, echographical and clinical monitoring, early reduction of maternal
      activity and cesarean deliveries. Our management of such pregnancies is of high
      quality as reflected by our obstetrical results. Lack of adequate management, as
      perceived by families of quadruplets, exists at two levels; a psychological (lack
      of psychological support) and a financial (lack of specific help).

PMID- 9014003
TI  - Pediatric hepatology: present and future.

PMID- 9014004
TI  - The assessment of the umbilical blood flow of the surviving twin after the
      intrauterine death of the other twin.
AB  - This paper summarizes our experience with Doppler velocimetry in survivors of
      intrauterine co-twin demise. In the first trimester, ten dichorionic deaths
      occurred; none of the survivors developed flow disorders. During the second
      trimester, there were three intrauterine demises, two of them were monochorionic
      and the survivors developed flow disorders: one presented transitory venous flow
      aberration, the other one an impaired development of diastolic flow. In the third
      trimester, two intrauterine deaths occurred. One case of twin to twin transfusion
      syndrome (TTTS) was complicated by the donor's death and the recipient showed a
      loss of diastolic flow. The second one happened during a dichorionic twin
      pregnancy. The survivor presented high systolic/diastolic daily ratio (S/D =
      7.8).

PMID- 9014005
TI  - Prenatal ultrasound diagnosis of cystic hygroma occurring in twin pregnancies.
AB  - Our study reports five cases of prenatal ultrasound diagnosis of nuchal cystic
      hygroma and early diagnosis for both fetus and mother. We observed that nuchal
      cystic hygroma is frequently associated to cytogenetic abnormalities, congenital
      structural anomalies and non-immune hydrops fetus universalis.

PMID- 9014006
TI  - Autoimmune component in individuals during immune response to inactivated
      combined vaccine against Q fever.
AB  - Serum samples from 20 individuals immunized with inactivated combined vaccine
      (ICV) against Q fever and 10 individuals that received placebo were investigated
      on days 14, 21, 28 and 60 after immunization by isotope specific enzyme-linked
      immunosorbent assay (ELISA) for the presence of antibodies directed to human IgA,
      IgM and IgG, and their fragments (F(ab')2, Fab, Fc). None of the subjects that
      received placebo exhibited significant increase of reactivity with any of the
      used antigens. By contrast, the sera of immunized individuals tended to show
      increased autoantibody activity with diverse antigens. Forty % of sera of
      immunized subjects exhibited anti-Fab activity, 20% of the sera recognized IgA,
      F(ab')2- and Fc-fragments, and 15% of the sera recognized IgG and IgM. Although
      there was wide variation in antibody levels and in isotypic heterogeneity of
      autoantibodies induced by immunization, anti-Fab autoantibodies were represented
      mainly by IgG and IgA isotypes but not IgM isotype. A direct correlation between
      the anti-Coxiella burnetii (anti-C.b.) antibody level and the anti-Fab IgG
      activity, and between the anti-C.b. antibody level and the anti-Fab IgA activity
      was found. In the group of vaccinees reacting strongly to the vaccine against Q
      fever, this correlation significantly increased for both the anti-Fab IgG and the
      anti-Fab IgA activities. No correlation was found with the sera in the group of
      the subjects that received placebo.

PMID- 9014008
TI  - Sequence analysis of VP7 gene of two Nigerian rotavirus strains.
AB  - The complete nucleotide sequences of gene 9 (VP7) of rotavirus strains MGH66 and
      RHIB55 isolated in northern and southern Nigeria, respectively, were determined.
      The sequence of either strain was 1062 nucleotides along with two potential
      glycosylation sites and two in-phase initiation codons encoding a protein of 326
      amino acids provided the first ATG codon was utilised. Comparison of the deduced
      amino acid sequences of VP7 of the strains with that of published sequences of
      serotype G1 strains and a representative strain of each of serotypes 2-6 and 8-14
      revealed > or = 91.41% and > or = 81.60% homology, respectively. The stool sample
      obtained from a diarrhoeic child in Maiduguri containing strain MGH66 was
      classified by polymerase chain reaction (PCR) technique as possessing a dual
      infection specificity of VP7 serotypes G1 and G3. The nucleotide sequencing,
      however, revealed the dual infection specificity of VP7 serotypes G1 and G8. The
      implications of nucleotide sequence analysis for serotyping of rotavirus strains
      originating from different geographical regions and for vaccine development are
      discussed.

PMID- 9014007
TI  - Influence of glycoproteins B, C and D on the conversion of virus-to-cell
      attachment from heparin sensitivity to resistance.
AB  - Glycoprotein C-negative (gC-) mutants of herpes simplex virus type 1 (HSV-1)
      derived from strains KOS and ANGpath were used to analyse the influence of
      soluble heparin on the phase of adsorption/attachment of HSV-1 to cells. A dose
      of 200 micrograms/ml heparin given 20 mins after infection of cells with the gC-
      positive (gC+) strains KOS and ANGpath at 4 degrees C reduced the adsorption of
      infective particles to 20-30% of the controls. A weaker heparin effect was
      observed with gC- mutants. However, also the gC- mutants exhibited a short
      heparin-sensitive phase. Mutations in amino acids of gB or gD at positions 854 or
      25 and 27, respectively, did not alter the attachment capacities of these HSV
      mutants in the presence of heparin despite their peculiar fusion properties and
      resistance to soluble gD. We conclude that HSV-1 strains exhibit a heparin
      resistant phase of attachment, which is determined by gC. Lack of gC delays the
      heparin-resistant attachment phase of HSV-1 to cells.

PMID- 9014009
TI  - Neutralization of human immunodeficiency virus type 1 (HIV-1) with antibody from
      carriers' plasma against HIV-1 protein p17.
AB  - It was investigated whether human antibody against HIV-1 protein p17 (anti-p17)
      in HIV carriers' plasma has the ability to neutralize the infectivity of HIV. By
      the pretreatment of HIV-1 with anti-p17 from HIV carriers, progeny HIV-1
      production from cells infected with virus pretreated with anti-p17 was suppressed
      and/or delayed. The neutralizing activity of anti-p17 was decreased in the
      presence of recombinant p17. The latter obviously masked the neutralizing
      activity of anti-p17. The relevant epitope(s) on p17 is located apparently on the
      surface of HIV virions and the binding of anti-p17 to p17 impairs the infectivity
      of HIV. This implies that anti-p17, if stably present in HIV carriers' plasma,
      may also play an important role in reducing the infectivity of HIV-1 in vivo.

PMID- 9014010
TI  - Growth of hepatitis A virus in murine cells.
AB  - In order to investigate the growth of hepatitis A virus (HAV) in murine cells,
      L929 cells of the established mouse cell line were transfected with the virion
      RNA or infected with the virions and examined for the formation of negative
      strand RNA and the rise of the viral infectivity titer. In both the transfected
      and infected cells, the formation of negative-strand HAV RNA was assayed by the
      reverse transcription-polymerase chain reaction (RT-PCR). In the transfected
      cells, infectious HAV of an average titer of 10(1.8) TCID50/dish was obtained.
      The experiment with the virion infection was further extended by using other
      mouse cell lines, namely Balb/3T3 clone A31, NIH/3T3, and Swiss/3T3. Here, only
      NIH/3T3 cells were found capable to support the formation of negative-strand HAV
      RNA. Thus some murine cell lines are considered to have a complete cellular
      machinery for supporting the growth of HAV, though the efficiency of virus growth
      therein was considerably lower as compared to that in the susceptible primate
      cells.

PMID- 9014011
TI  - Maturation of respiratory syncytial virus within HEp-2 cell cytoplasm.
AB  - Electron microscopy of HEp-2 cells infected with respiratory syncytial virus
      (RSV) strain Long revealed the maturation of RSV on an ultrastructural level. The
      results showed that the virus maturated by two different pathways. In one of
      them, the virus assembled and matured before reaching the plasma membrane on the
      internal vesicle membrane within cytoplasm. The mature virus was delivered to the
      plasma membrane and to the extracellular space most likely by the transport
      vesicles and exocytosis. In the other pathway, the virus matured on the plasma
      membrane as described with other members of the family Paramyxoviridae. Using
      monoclonal antibodies (MoAbs), we localized viral nucleoprotein (NP) and envelope
      proteins in cytoplasm by immunoelectron microscopy (IEM).

PMID- 9014012
TI  - Genotypic identification of three new strains of spotted fever group rickettsiae
      isolated in China.
AB  - Polymerase chain reaction (PCR) and restriction endonuclease fragment length
      polymorphism (RFLP) analysis were used to characterize the genotypic diversity of
      three isolates of spotted fever group (SFG) rickettsiae isolated from ticks in
      China. A primer pair designed from DNA sequence encoding 190 K protein antigen of
      R. rickettsii and genomic DNAs obtained from the isolates were used in PCR. The
      PCR products were cleaved with restriction endonucleases PstI and RsaI, and the
      digestion patterns were analyzed by polyacrylamide gel electrophoresis (PAGE) and
      compared with those of all known species and strains of SFG rickettsiae. The
      results showed that three isolates had the same PCR products as the other SFG
      rickettsiae under comparison. HL-93 strain, isolated from Hemophysalis concinna
      ticks collected in Hulin County, Heilongjiang Province, had unique PstI digestion
      pattern among SFG rickettsiae; strains BJ-93 and 053, isolated from Dermacentor
      sinicus and Haemaphysalis concinna ticks collected in Changping County, Beijing
      City, and Suifenhe City, Heilongjiang Province, respectively, had the same PstI
      and RsaI digestion patterns as strains R. sibirica 246, BJ-90 and IMTO-85. The
      present study demonstrated that the BJ-93 and 053 strains were genotypically
      identical with R. sibirica and the HL-93 strain was genotypically unique among
      SFG rickettsiae.

PMID- 9014013
TI  - Interferon-omega suppresses hepatitis B surface antigen production in human
      hepatoma cell line.
AB  - Biological activities of human interferon (IFN) omega are less well characterized
      than those of other type I human IFNs. We compared the ability of recombinant IFN
      omega, IFN-alpha 2 and IFN-gamma to inhibit the production of viral hepatitis B
      surface antigen (HBsAg) in the human hepatoma cell line PLC/PRF/5. The results
      demonstrated that the capacity of IFN-omega to suppress the HBsAg synthesis was
      similar to that of IFN-alpha 2. The kinetics of the inhibitory effect of IFN
      gamma differed from those of the two other IFNs.

PMID- 9014014
TI  - Experimental infection with a persistent influenza C virus variant leads to
      prolonged genome detection in the chicken lung.
AB  - A persistent variant of influenza C virus was used to infect chickens by
      intraamniotic (i.a.) inoculation. The infected hatchings were analyzed for virus
      production in different tissues and for the continuous presence of viral RNA
      genomes. The permissiveness for infection was demonstrated primarily for the
      chicken lung, besides other organs. Viral antigens could be detected by indirect
      immunofluorescence staining for a period of 8 days and reisolates were obtained
      mainly at early time points post infection (p.i.). Nested reverse transcription
      polymerase chain reaction (RT-PCR) directed to 3 genomic sequences was positive
      at least until day 53, whereby no distinct end point was determined. These
      experiments provide first evidence for the long-term stability of influenza C
      virus RNA segments in vivo.

PMID- 9014015
TI  - Differences between original strains and their mouse-adapted variants of human
      (H1) and avian (H2) influenza A viruses in the reaction with cross-neutralizing
      monoclonal antibody recognizing conformational epitope.
AB  - Human (H1) and avian (H2) influenza A viruses and their mouse-adapted (MA)
      variants were studied in radioimmunoprecipitation assay (RIPA) and infectivity
      neutralization test using a monoclonal antibody (MoAb) directed against a
      conserved antigenic epitope in the stem region of the haemagglutinin (HA) and
      reacting both with H1 and H2 subtypes of HA. Whereas the MA variant of avian
      influenza A virus differed from the original strain in RIPA and neutralization
      tests, no differences were observed between the original human strain and its MA
      variant, as well as between the original H1 and H2 strains.

PMID- 9014016
TI  - Epstein-Barr virus nuclear antigen 1 makes a complex during the early stage of
      immortalization of human lymphocytes.

PMID- 9014018
TI  - Alcohol intake in a rural village: physical signs and biological markers
      predicting excessive consumption in apparently healthy people.
AB  - Four hundred and ninety-two (232 males and 260 females) randomly selected
      inhabitants older than 15 years of La Esperanza, a rural village of Tenerife,
      have been inquired about their daily alcohol intake, analyzing the relationship
      between this parameter and sex, age, marital status, educational level, job and
      smoking habit, physical signs, and biological markers of excessive ethanol
      consumption. One hundred and seventy-four out of them (35.4%) were teetotalers,
      while 318 (64.6%) consumed alcoholic beverages; 18.2% (34.1% of the males and
      4.2% of the females) referred excessive ethanol consumption (more than 80 g/day
      and 40 g/day, respectively). Men consumed 62.3 +/- 4 g/day ethanol and women, 8
      +/- 1 g/day. The distribution of the population according to the amount of
      ethanol consumed fits into Lederman's curve, most of the individuals being
      consumers of small amounts of ethanol. Male sex, middle age, married or separated
      status, unskilled job, sometimes unemployed, low educational level, daily
      drinking (mainly wine), and smoking, were all related to a higher ethanol
      consumption. When assessed by logistic regression, only liver enlargement,
      parotid swelling, retches and tremor in the morning, and hoarseness, out of the
      physical signs, showed independent predictive value as indicators of excessive
      consumption as well as serum GGT, ASAT, MCV, and urate levels out the biological
      markers. When all those physical and analytical signs that had previously shown
      predictive independent value are analyzed together, all the five physical signs
      (liver enlargement, parotid swelling, retches and tremor in the morning, and
      hoarseness) but only urate, out of the biochemical markers, showed independent
      predictive value.

PMID- 9014019
TI  - Effect of calcium channel blocker diltiazem on some depressant actions of ethanol
      in UChA and UChB rats.
AB  - Rats genetically selected for their different ethanol voluntary consumption, UChA
      (low consumer) and UChB (high consumer) were used. Naive UChA and UChB rats or
      submitted to ethanol chronic exposure, received an i.p. dose of ethanol (2.76
      g/kg) alone or 30 min after an oral dose of diltiazem (10 mg/kg), a calcium
      channel blocker. A significant potentiation of the narcosis and hypothermia
      induced by the dose of ethanol was observed in UChA diltiazem-pretreated rats not
      previously exposed to ethanol, while no potentiation in narcosis time appears in
      UChA rats chronically exposed to ethanol that acquire tolerance. In the UChB line
      of rats, diltiazem did not potentiate ethanol depressant actions in naive or
      chronic ethanol-exposed rats. Diltiazem did not modify ethanol blood levels.
      These results indicate that the inhibition of voltage-dependent calcium channels
      can exaggerate ethanol-induced effects in naive rats but not when tolerance was
      developed. Results suggest that UChB rats may have some innate tolerance that may
      be due to genetic difference in calcium channel function.

PMID- 9014017
TI  - Ethanol affects hypothalamic neurons projecting to the hippocampus and inhibits
      dentate granule cell LTP.
AB  - In previous studies we demonstrated that ethanol inhibition of hippocampal
      granule cell long-term potentiation (LTP) is mediated by angiotensin II (AII),
      and the inhibition can be blocked by losartan, a specific AII receptor
      antagonist. The purpose of the present study was to demonstrate that this low
      dose ethanol inhibition of dentate granule cell LTP induction is mediated by
      lateral hypothalamic (LH) afferents that project to the granule cells. In
      urethane anesthetized rats, we compared the effects of ethanol infusion, 6.0
      microliter/30 min, by means of an open-ended push-pull type cannula, in both the
      LH and the dentate gyrus, on dentate granule cell LTP. Results demonstrate a dose
      dependent inhibition of LTP induction when the LH is perfused that can be blocked
      by losartan, 10 mg/kg i.p.. Four doses of ethanol were used: 5, 10, 20, and 30
      mM. There was no effect when the dentate gyrus was infused with 30 mM ethanol and
      normal granule cell LTP was observed. Also, these results demonstrate for the
      first time a low-dose ethanol effect on a physiological function, LTP in a
      specific neural pathway, directly related to the anterograde amnesia produced by
      ethanol on short-term memory. Therefore, these data support our hypothesis that
      ethanol inhibition of LTP induction at the medial perforant path-granule cell
      synapse can be attributed to a presynaptic release of AII and cannot be explained
      in terms of a direct postsynaptic effect on the granule cells.

PMID- 9014020
TI  - Prenatal high saturated fat diet modifies behavioral effects of prenatal alcohol
      exposure in rats.
AB  - Pregnant rats were fed a control diet, a high saturated fat diet, or a high
      polyunsaturated diet lacking in vitamin E and zinc, for 6 weeks prior to breeding
      and continued to consume these diets during pregnancy. Beginning on gestation day
      8, rats in each diet group were intubated with 5.3 or 0 g/kg alcohol. Rats in the
      0 and 3 g/k group were pair fed to those in their respective 5 g/kg groups. A
      fourth group received one of the three diets ad lib, and was not intubated. On
      postnatal day 20, offspring were tested for locomotor activity and head-dipping
      behavior. Animals prenatally exposed to alcohol were more active and made more
      head dips than pair-fed controls, but only if their mothers consumed the control
      diet. Alcohol had an opposite effect on offspring whose mothers consumed the high
      saturated fat diet, and had no effect on animals consuming the high
      polyunsaturated/no vitamin E or zinc diet. These preliminary results suggest that
      dietary fat may modify the behavioral effects of prenatal alcohol exposure. This
      effect may be the result of the stabilizing effect of saturated fats on cell
      membranes which increases their resistance to perturbation by alcohol.

PMID- 9014021
TI  - Neuropsychological functioning in sons of active alcoholic, recovering alcoholic,
      and social drinking fathers.
AB  - Sons of active alcoholic, recovering alcoholic, and social drinking fathers were
      administered neuropsychological tests to assess whether they differ in their
      cognitive functioning. Multivariate analyses of variance showed that sons of
      active alcoholic sons perform significantly worse on visuospatial, memory, and
      attentional tasks as well as general intellectual functioning than sons of social
      drinking fathers. The sons of recovering alcoholic fathers showed no significant
      difference from social drinking fathers in their cognitive functioning. These
      results suggest that the clinical type of the alcoholic father (i.e., inability
      to abstain, more severe alcoholic vs. ability to abstain, less severe alcoholic)
      may be an important factor that determines whether offspring of alcoholics have
      neuropsychological deficits.

PMID- 9014023
TI  - Amphetamine and fenfluramine suppress ethanol intake in ethanol-dependent rats.
AB  - Alcohol intake or preference for alcohol has been attributed to concomitant
      dopamine and serotonin dysfunction in rats. Amphetamine and fenfluramine,
      administered alone, have been shown to reduce food and fluid intake as well as
      alcohol consumption while acute coadministration of these agents has been shown
      to suppress audiogenic seizure in rats withdrawn from alcohol. The present study
      was designed to assess the effectiveness of chronic amphetamine and fenfluramine
      coadministration on reducing alcohol intake. Chronic coadministration of
      amphetamine (2 mg/kg) and fenfluramine (8 mg/kg) reduced alcohol consumption
      during choice trials in both alcohol-dependent and alcohol-nondependent rats
      while not affecting water intake. The findings indicate that coadministration of
      amphetamine and fenfluramine, a treatment effective in reducing alcohol
      withdrawal seizures, also selectively attenuates alcohol consumption.

PMID- 9014022
TI  - Zinc, copper, manganese, and iron in chronic alcoholic liver disease.
AB  - Ethanol consumption and/or liver damage may alter liver content of several trace
      elements, as iron, zinc, copper, and manganese. This alteration may play a role
      on ongoing liver fibrogenesis. Based on these facts we have determined liver,
      serum, and urinary Mn, Cu, Zn, and Fe levels in a group of alcoholic cirrhotics
      and noncirrhotics with normal renal function, comparing them with those of
      controls. We have observed low liver zinc and high liver copper--this last in
      relation with histomorphometrically determined total amount of liver fibrosis-
      and manganese contents in cirrhotics, together with increased excretion of zinc
      and iron and decreased excretion of manganese. Zinc, iron, and copper excretion
      kept a relation with data of severity of cirrhosis, including mortality in the
      case of urinary copper, independently of the use of diuretics. Thus, liver copper
      and urinary iron, zinc, and copper excretion seem to be related with data of
      severity of chronic alcoholic liver disease. Low urinary manganese excretion may
      play a role on liver manganese overload.

PMID- 9014024
TI  - Inhibition of platelet aggregation in whole blood after exposure of rats to
      alcohol by inhalation.
AB  - The dose-effect relationship between blood alcohol concentration (BAC) and
      altered platelet function was examined in whole blood in a rat model of alcohol
      exposure by inhalation, using the impedance method of ex vivo whole blood
      platelet aggregation. With rates of alcohol addition to the chamber air inflow
      from 29 to 56 mg ethanol/l air/min, BAC was dependent on duration of exposure and
      concentration of alcohol in the air. Next, 3, 6, and 9 h exposures to the highest
      delivery rate were used, and platelet aggregability was tested. After 9 h, BAC
      reached 453 +/- 16 mg% and aggregation responses to three doses of collagen were
      significantly lower than in control blood (p < 0.01). Less consistent inhibition
      was observed with arachidonic acid and ADP, and also when exposure duration was
      reduced. However, some significant inhibition of collagen-induced aggregation (p
      < 0.05) was observed with BAC as low as 127 +/- 15 mg%. These experiments
      demonstrate that in vivo alcohol exposure inhibits, in a concentration-dependent
      manner, ex vivo rat whole blood platelet aggregation, at BACs readily attained in
      humans by ingestion.

PMID- 9014025
TI  - Morphine enhances selection of both sucrose and ethanol in a two-bottle test.
AB  - The influence of a low dose of morphine on the self-selection of alcohol and
      sucrose solutions is investigated. When given a choice between sucrose sweetened
      ethanol and plain water, rats show a significant preference for the sweetened
      ethanol. However, when given a choice between sweetened ethanol and sweetened
      water, rats increase consumption of sweetened water. These results suggest that
      the low-dose morphine enhancement of sweetened alcohol solutions is mediated by
      the reinforcing properties of sucrose not ethanol. However, when rats receive
      small doses of morphine and a choice between unsweetened ethanol and water, the
      rats increase consumption of ethanol. Therefore, a low dose of morphine enhances
      the self-selection of both sucrose and ethanol solutions. This provides
      additional confirmation that opioids may enhance the rewarding properties of a
      variety of appetite reinforcers.

PMID- 9014026
TI  - 5-HT3 receptor antagonist, tropisetron, does not influence ethanol-induced
      conditioned taste aversion and conditioned place aversion.
AB  - Numerous works have demonstrated an interaction between 5-HT3 receptor
      antagonists and some of the effects of ethanol (EtOH) using biochemical,
      electrophysiological, and behavioral techniques. Thus 5-HT3 antagonists are
      capable of reducing EtOH-induced release of dopamine in the nucleus accumbens,
      EtOH-induced hyperlocomotion, and voluntary EtOH consumption in laboratory
      animals. In addition to its rewarding effect, EtOH possesses aversive properties
      as demonstrated in the conditioned taste aversion (CTA) and conditioned place
      aversion (CPA) paradigms. The role of 5-HT3 receptors in aversive effects of EtOH
      remains, however, unknown. We decided to study the effect of 5-HT3 antagonist,
      tropisetron, on aversive properties of EtOH (1.5 g/kg i.p.) in rats using the CTA
      and CPA models. In addition, effect of tropisetron on morphine (Mf)-induced CTA
      (10.0 mg/kg SC) was investigated. Tropisetron (0.001-0.5 mg/kg) did not influence
      CTA produced by EtOH and Mf. When given alone, it failed to produce any taste
      conditioning. Furthermore, tropisetron did not modify CPA induced by EtOH. Our
      results suggest that 5-HT3 receptors are not involved in aversive effects of
      acute doses of EtOH.

PMID- 9014027
TI  - Glucose and the insulin-releasing drug tolbutamide attenuate the effects of
      morphine and angiotensin on alcohol consumption.
AB  - Animals studies have shown that insulin injections reduce alcohol intake,
      implicating glucoregulatory processes in alcohol consumption. Angiotensin (ANG)
      II reduces alcohol intake and promotes glycogen breakdown in the liver but no
      studies have assessed the role of glucoregulatory processes in ANG II's effect.
      Similarly, glucose injections attenuate the analgesic and cognitive effects of
      opiates, yet no studies have assessed the effect of glucose on the well
      documented ability of opiates to enhance alcohol consumption. The present
      experiments further examine the role of glucoregulatory processes in alcohol
      intake by assessing the effect of glucose injections on morphine-enhanced alcohol
      consumption and by evaluating the effect of the insulin-releasing drug,
      tolbutamide, on ANG II-reduced alcohol consumption. Adult male Wistar rats
      acquired alcohol drinking using the limited access procedure that offers daily 40
      min access to both 6% w/v alcohol and water and ensures reliable alcohol drinking
      in bouts large enough to produce pharmacologically relevant intakes. Experiment
      1: after intake stabilized, four groups of rats were first pretreated with
      vehicle injections and in the next phase, three of the four groups received
      either 50, 100, or 200 mg/kg glucose intraperitoneally (i.p.) prior to access to
      alcohol. Neither the vehicle injections nor any of the glucose doses had an
      effect on alcohol intake. In the final phase all groups continued to receive
      their respective glucose doses or vehicle but were now also treated with 5 mg/kg
      morphine sulphate i.p. prior to alcohol access. Morphine stimulated alcohol
      intake to a similar degree in all groups except the 200 mg/kg group, which showed
      a significant attenuation in morphine-enhanced alcohol intake. Experiment 2:
      after intake stabilized, different groups of rats were pretreated with vehicle
      injections and in the next phase received either 5, 25, 50, or 100 mg/kg
      tolbutamide or vehicle subcutaneously (s.c.) prior to alcohol access. The vehicle
      injections did not alter alcohol intake, and only the 100 mg/kg dose of
      tolbutamide produced a reduction in alcohol intake. In the final phase the groups
      continued to receive their respective doses of tolbutamide or vehicle but were
      also treated with 400 micrograms/kg ANG II s.c. immediately prior to alcohol
      access. ANG II reduced alcohol intake a similar extent in the groups pretreated
      with 5-50 mg/kg tolbutamide. However, the 100 mg/kg dose of tolbutamide
      significantly attenuated ANG II's ability to reduce alcohol intake. These results
      demonstrate that manipulations that engage glucoregulatory processes can
      influence the mechanism(s) by which morphine and angiotensin respectively
      increase and decrease alcohol drinking.

PMID- 9014028
TI  - The effects of single and repeated episodes of thiamin deficiency on memory in
      alcohol-consuming rats.
AB  - The underlying pathogenesis of Korsakoff's syndrome, an amnesic disorder most
      commonly found in alcoholics, is not well understood. Chronic alcoholism is
      associated with thiamin deficiency and current thinking is that this may be the
      causal factor. In Experiment 1, rats were given a 20% (v/v) ethanol/water mix as
      their only source of fluid for 156 days. Three groups were made thiamin deficient
      through the combination of a thiamin-deficient diet and the centrally acting
      thiamin antagonist pyrithiamin hydrobromide, after 4, 15, and 26 weeks exposure
      to ethanol, respectively. The control group was given ad lib access to laboratory
      chow and water throughout this period. There were no differences between groups
      on either the working or reference versions of the Morris water tank paradigm. In
      Experiment 2, to test the hypothesis that a single bout of thiamin deficiency,
      with or without concurrent alcohol intake, is not sufficient to cause severe
      memory impairments, two groups of rats were subjected to three bouts of thiamin
      deficiency. One of these groups consumed an ethanol/water mix, the other tap
      water. A third group was made thiamin deficient on only one occasion. The control
      group was not made thiamin deficient and consumed lab chow and tap water
      throughout. Once again, there were no between-group differences in the data
      derived from testing in either the eight-arm radial maze or the Morris water tank
      task. These experiments indicate that the aetiology of Korsakoff's syndrome is
      more complex than previously thought.

PMID- 9014029
TI  - Chronic ethanol ingestion produces cholinergic hypofunction in rat brain.
AB  - Alterations in cholinergic function due to prolonged ethanol exposure (up to 9
      months) were assessed by choline acetyltransferase (ChAT) activity and high
      affinity choline uptake (HAChU) in three brain regions of the Long-Evans rat:
      frontal cortex, parietal cortex, and region of the nucleus basalis of Meynert
      (NbM). No statistically significant changes were found in ChAT activity in the 3
      month group; however, ChAT activity was decreased in both the frontal cortex (
      32%) and NbM region (-22%) after 6 months of ethanol exposure. ChAT activity in
      the parietal cortex was increased 30% after 6 months. Nine months of exposure
      significantly decreased ChAT activity in all three brain regions. No significant
      differences were observed in high-affinity choline uptake after 3 months of
      ethanol exposure. However, after 6 months of ethanol exposure HAChU was decreased
      to 51% of control values in the frontal cortex. There was a simultaneous increase
      in HAChU to 43% and 178% of control values in the NbM and parietal cortex,
      respectively. However, choline uptake was significantly decreased in the frontal
      cortex and NbM region after 9 months of exposure. The results indicate a
      neurotoxic effect of prolonged intake of ethanol on the basal forebrain
      cholinergic projection system, which may cause impairment of cholinergic
      innervation of target areas of the basal nucleus complex.

PMID- 9014030
TI  - Alcohol-induced thymocyte apoptosis is accompanied by impaired mitochondrial
      function.
AB  - This study examines the effects of chronic alcohol consumption on thymic
      apoptosis with or without pretreatment with E. coli lipopolysaccharide (LPS).
      Apoptotic cell death of thymocytes was monitored by DNA fragments in gel
      electrophoresis and the appearance of apoptotic cells by flow cytometry. Changes
      in mitochondrial membrane potential (MMP), as indicated by 3,3'
      dihexyloxacarbocyanine iodide [DiOC6(3)] uptake, and hydrogen peroxide (H2O2)
      production as indicated by oxidation of 2',7'-dichlorofluresin diacetate (DCFH
      DA), were used to assess altered mitochondrial function. Glutathione levels were
      also determined to obtain information concerning alterations in the antioxidant
      potential in the cells. Male Sprague-Dawley rats, fed a nutritionally adequate
      liquid diet for 8-9 weeks, were divided in four groups: 1) saline-injected, diet
      controls; 2) LPS-injected, diet controls; 3) saline-injected, alcohol-consuming;
      and 4) LPS-injected, alcohol-consuming animals. LPS (0.5 mg/kg in 4 ml saline) or
      saline (4 ml) was continuously infused i.v. for 12 h before the experiments. The
      results showed that the weight and cell numbers of thymus from the chronic
      alcoholic rats were significantly less than values found in diet controls.
      Administration of LPS aggravated thymic apoptosis, as indicated by the presence
      of significant DNA fragments in gel electrophoresis and increased rate of
      apoptotic cells in flow cytometry. The alcohol-induced apoptotic changes were
      also accompanied by decreased MMP, indicating impaired mitochondrial function.
      Although H2O2 production by the total thymocyte population did not show marked
      changes among the experimental groups, the subpopulation of thymocytes exhibiting
      low H2O2 production was increased markedly in the LPS-treated groups. Ethanol
      consumption or LPS treatment decreased total glutathione concentration in the
      thymocytes. In summary, 1) chronic administration of alcohol induces atrophy of
      the thymus gland; 2) apoptosis is a major factor in thymic atrophy under these
      conditions; 3) chronic alcohol consumption is accompanied by alterations in
      mitochondrial function of the thymocytes, as indicated by decreased MMP and an
      increase in the low H2O2-producing cell subpopulation; 4) chronic alcohol abuse
      may impair intracellular defense mechanisms as reflected by the depletion of the
      intracellular antioxidant, glutathione; and 5) administration of LPS further
      enhances thymic apoptosis in chronic alcohol-consuming rats, suggesting that the
      dual insults of infection and chronic alcoholism exaggerate in vivo
      immunosuppression.

PMID- 9014055
TI  - Genetics and colorectal cancer: basic science meets clinical practice.

PMID- 9014056
TI  - Reoperation for recurrent thymoma: experience in seven patients and review of the
      literature.
AB  - The authors analysed retrospectively seven patients who underwent reoperation for
      recurrent thymoma. Patients have been categorised according to the classification
      of thymic epithelial tumours proposed by Masaoka et al. (29). In addition,
      patients have been subgrouped according to pleural invasion as defined by Haniuda
      et al. (15). Thus three substages were proposed as follows: p0-no adhesion to the
      mediastinal pleura; p1-patients with fibrous adhesion to the mediastinal pleura
      without microscopic invasion; p2-patients with microscopic invasion into the
      mediastinal pleura. At the initial operation, two patients were in Stage I, four
      Stage II, and one in Stage III. All Stage I patients were classified as p1, and
      of the four patients in Stage II one was classified as p0 and three patients as
      p2. One Stage III patient was classified as p2. Disease-free survival ranged from
      two years and four months to 20 years and two months. All patients underwent
      reoperation without preoperative treatment. Recurrent disease was aggressively
      resected from the pleura in six patients, mediastinum in four patients, lung in
      three patients, and diaphragm in three patients. Two patients refused further
      postoperative treatment. Adjuvant radiotherapy was administered to five patients;
      chemotherapy was added to the postoperative treatment of three patients with more
      advanced recurrent disease. Five patients were alive, free from any detectable
      tumour recurrence, one year and nine months to five years and four months after
      reoperation. In two patients with exacerbation of myasthenia gravis, reoperation
      was followed by complete remission of myasthenic symptoms. One patient died of
      post-radiation pulmonary fibrosis 13 months after reoperation, and one patient
      died of disease two years and two months after the second operation. Our findings
      indicate that an aggressive surgical approach to recurrent thymoma is justified
      and can be followed by prolonged disease-free survival.

PMID- 9014057
TI  - Gastric cancer: surgical management and prognosis.
AB  - The experience of the Department of Surgery of Oulu University Hospital, Finland,
      in the treatment of 203 consecutive patients (129 men and 74 women, mean age 64.9
      years) with primary gastric cancer during the five-year period from 1983 to 1987
      is reviewed. 196 (96.6%) patients underwent surgery; radical gastrectomy with
      limited lymphadenectomy in 88 (43.3%) cases, palliative gastric resections in 47
      (23.3%) cases and symptomatic bypass procedures in 27 (13.3%) cases.
      Postoperative complications occurred more frequently after total than after
      subtotal gastrectomy. Overall postoperative mortality was 9.2%. The five-year
      survival was 21.1% for all patients and 45.5% for curatively operated patients.
      Univariate analysis indicated that tumour size, location, gross appearance,
      degree of gastric wall invasion, presence of lymph node and/or distant
      metastases, and operative procedures were the significant prognostic factors of
      survival. In a Cox multivariate analysis on the T stage and presence of distal
      metastases independently affected survival. Our results show that besides early
      detection, the standardisation of surgical procedures (extent of gastrectomy and
      lymphadenectomy) as well as substantial decrease in postoperative complications
      and mortality rates are of importance in the improvement of the outcome of
      surgery for gastric cancer.

PMID- 9014058
TI  - The value of herniography in the diagnosis of unexplained groin pain.
AB  - Herniographies were performed on 106 outpatients with obscure groin pain. A total
      of 39 hernias were found in 38 patients (36%) and the 46 patients either operated
      on (40 patients) or who had undergone laparoscopy (six patients), included one
      false positive and two false negative ones. All three cases were inpatients who
      had earlier undergone surgery for inguinal hernia 27% of the patients with a
      normal clinical finding (19/70), 67% of those with previous inguinal herniotomy
      (8/12) and 50% of those with symptoms suggestive of hernia (12/24) had diagnostic
      findings on herniography. Thirteen out of the 48 women (27%) and 25 of the 58 men
      (43%) had positive finding at herniography. The valve of herniography was that 56
      patients were spared subsequent surgical exploration because of normal
      herniographic finding. Our results indicate that herniography is a useful tool
      for the examination of patients with unexplained groin pain.

PMID- 9014059
TI  - Surgical complications after total thyroidectomy and resections for
      differentiated thyroid carcinoma.
AB  - Differentiated thyroid carcinoma often has a favourable prognosis. However, there
      is no unanimity about the surgical procedure used. In this analysis we evaluated
      the surgical complications of 178 patients operated on for differentiated thyroid
      carcinoma during a 12-year period. 110 of the patients were operated in one
      session and 68 in two. Total thyroidectomy was performed in 106 patients and
      ipsilateral lobectomy together with contralateral subtotal resection in 72
      patients. Tumour was bilateral or multicentric in 59 patients (33%).
      Hypoparathyroidism occurred in eight patients (4%), without differences between
      total thyroidectomies and lobectomy plus subtotal resections. Hypoparathyroidism
      tended to be more common after completion resection than after completion
      thyroidectomy (4/28 vs 1/40; P = 0.08). Accidental injury to the recurrent
      laryngeal nerve occurred in one patient (0.6%) during a contralateral resection.
      During a median follow-up of 4.5 years, tumour recurrence was detected in 22
      patients (12%). In papillary carcinoma it was more common in patients who had
      underwent lobectomy plus contralateral resection than after total thyroidectomy
      (11/60 vs 3/88; P < 0.01). However, the median follow-up times were unequal. In
      conclusion, total thyroidectomy and even completion thyroidectomy is as safe as
      less radical lobectomy together with contralateral resection. Thus, total
      thyroidectomy should be offered to all patients with differentiated thyroid
      carcinoma until there is a reliable method to recommend for those patients who
      can be treated with less radical procedures.

PMID- 9014060
TI  - Experiences with mobile extracorporeal shock wave lithotriptors in northern
      Finland.
AB  - A total of 285 renal units in 248 patients received 424 extracorporeal shock wave
      lithotripsy (ESWL) treatments with mobile lithotriptors for renal and ureteric
      stones at Oulu University Hospital. Treatments were given approximately once a
      month (1-2 days) with 7-10 treatments per day. The overall success at 1-3 months
      was 88% (74% stone-free). Success with single renal stones was 88% (70% stone
      free), that with multiple renal stones 78% (62% stone-free) and that with
      ureteric stones 93% (89% stone-free). Retrograde manipulation appeared to be a
      safe and effective treatment for patients with obstructing ureteric stones
      obliged to wait for the next treatment session. The most serious complication was
      one perirenal haematoma requiring transfusion. The results compare favourably
      with those achieved with fixed lithotriptors and prove that mobile lithotriptors
      are suitable for small centres.

PMID- 9014061
TI  - Predictive value of distal pressure measurements in critical leg ischaemia.
AB  - In a retrospective study 110 consecutive patients with 145 critically ischaemic
      legs were assessed. Based on a three-month follow-up the predictive values for
      leg survival of the ankle and toe pressure measurements were determined. 25% of
      the legs had been amputated. The ankle and toe pressures as well as the ankle
      brachial index (ABI) were lower in the amputated than in the nonamputated group
      but considerably overlapping. Mean values for ankle pressures were 32 and 42 mmHg
      (P < 0.05), for toe pressures 16 and 20 mmHg (P < 0.05) and for the ABI 0.26 and
      0.32 (P < 0.01). According to the present results a single ankle, toe or ABI
      measurement had no predictive value as to the risk of amputation. It can,
      however, be used as an adjunctive measure to supplement clinical examination.

PMID- 9014062
TI  - Validity and reproducibility of transit time flowmetry.
AB  - A new intraoperative method for blood flow measurement, ultrasonic transit-time
      flowmetry, was validated regarding its variation and error of measurement. Both
      common iliac arteries of five piglets were dissected under inhalation
      anaesthesia. Three probes, calibrated by the manufacturer, were used. Variability
      was evaluated by repeated measurements from the native artery and under
      exsanguination controlled with a withdrawal pump. The errors of measurement were
      calculated by comparing the flow with the exsanguinated volume by time. For each
      vessel 34-36 separate exsanguinations were carried out, with flow ranging from 10
      to 500 ml/min. The coefficients of variation for the two 5 mm probes measured
      from the native artery were 3.8% and 4.2%, and 4.5% for the 3 mm probe. With the
      use of the withdrawal pump the coefficients were 2.5%, 2.2% and 2.1%,
      respectively. The two 5 mm probes showed a mean error of measurement of 0.7% (95%
      confidence interval (CI) was -10.4 to 13.25) and -11.4% (95% CI -20.6 to -1.1),
      while the error for the 3 mm probe was 3.4% (95% CI -18.1 to 14.0). The small
      variation of all probes indicated a good reproducibility. With accurate
      calibration of the probes, ultrasonic transit-time flowmetry appears to be a
      valid and adequate method for clinical use.

PMID- 9014063
TI  - Perioperative volume effect of HES 120/0.7 compared with dextran 70 and Ringer
      acetate.
AB  - Hydroxyethyl starch 120 (HES 120/0.7, Plasmafusin) is the smallest medium
      molecular weight HES preparation used as a plasma substitute for all clinical
      purposes. We compared the volume and colloid osmotic effect of 6% HES 120 with 6%
      dextran 70 and Ringer's solution during and after surgery with minimal blood
      loss. Patients (n = 48) having general anaesthesia were randomly divided into six
      groups. A thirty-minute bolus infusion was started at the induction of
      anaesthesia, and thereafter the infusions were continued at two different rates
      for five hours. The volume of the bolus was 10% and 30% of the calculated volume
      (CPV) in colloid and Ringer groups, respectively. The constant infusion rates
      were 2% and 6% of the CPV for the colloids, and 10% and 20% for the two Ringer
      groups. Blood samples for the measurement of serum proteins and colloid osmotic
      pressure (COP) were obtained before induction, after the bolus, and thereafter
      hourly throughout the study. Albumin, prealbumin and total serum protein
      concentrations were used to calculate relative plasma volumes. After the bolus
      infusion, plasma volumes increased significantly in all six groups and the
      increments were sustained throughout the study. At the lower infusion rates of
      the volume changes of HES and Ringer groups were almost identical and comparable
      to dextran group up to the third floor. At the higher infusion rates, dextran 70
      produced greater plasma volume expansions than HES 120, and the volume effect of
      Ringer's solution was clearly exceeded by both colloids. The hourly estimated
      half-lives of dextran were constantly longer compared with HES. With both
      infusions rates the COPs of dextran and HES groups were higher compared with
      Ringer groups. There were no differences in COP between the dextran and HES
      groups. It is concluded, that in this clinical setting the volume effect of 6%
      dextran 70 exceeds that of the HES 120/0.7, and that both colloids are superior
      to Ringer's solution.

PMID- 9014064
TI  - Clinical results and survival of cementless revisions after 49 to 93 months.
AB  - The results of 93 unselected consecutive cementless revision hip arthroplasties
      are reported. The patients' average age was 67 years, and the average follow-up
      was 62 months. The preoperative modified Merle d'Aubigne hip score averaged 9.7
      (range 4-17) and the latest postoperative score was 13.7 (range 9-18). Twenty
      five hips were rerevised and two await rerevision. Survivals of acetabular and
      femoral components at five years were 77 and 76% correspondingly. Radiographic
      examinations revealed migration in three acetabular components and seven femoral
      components (not yet rerevised). The results of the revisions with threaded
      acetabular components and with femoral components with madreporic or
      macrotextured surface were especially poor.

PMID- 9014065
TI  - Revision total hip replacement using the bias proximal porous-coated femoral
      component.
AB  - Revision total hip replacement (THR) to replace the loose femoral component using
      BIAS proximally porous-coated femoral revision stem was followed up in 39
      patients for five years. In six cases a new revision of the stem was carried out
      for symptomatic stem loosening and five more were definitely loose and in 15
      cases radiographs revealed clear radiolucent periprosthetic zones evidencing
      fibrous integration. The survival of the BIAS revision stem was 83% after five
      years. The mean Harris hip score (HHS) was 75 points and the final result was
      excellent in six, good in eight, fair in four and poor in 16 cases. The outcome
      was unacceptably poor and the use of this stem should be abandoned in THR
      revisions.

PMID- 9014066
TI  - Absorbable pins in the treatment of hand fractures.
AB  - Open reduction and internal fixation with absorbable devices was used to treat 32
      fractures of the hand at our department. The clinical results were reviewed in 20
      patients with an average follow-up of 4.5 years. There were 17 metacarpal
      fractures, 12 phalangeal and three carpal fractures. Thirty fractures were intra
      articular. Subjectively 15 of the 20 patients indicated their satisfaction with
      the outcome of the treatment. Redisplacement of fixation occurred in two
      Bennett's fractures. A minor redisplacement was observed in one comminuted and in
      one noncomminuted phalangeal intra-articular fracture. A foreign-body reaction
      occurred in two patients with a Bennett's fracture and in one with a trapezoid
      fracture. A wound infection occurred in one patient with a Bennett's fracture and
      in one patient with a phalangeal fracture. The use of absorbable implants showed
      promising results in the intra-articular fractures of metacarpal and phalangeal
      bones with the exception of the Bennett's fractures, where the outcome was less
      favourable. The number of patients in the study was limited and for a more
      definitive conclusion a larger series of fractures of the hand should be
      analysed.

PMID- 9014067
TI  - The effect of enoxaparin in prevention of deep venous thrombosis in hip and knee
      surgery--a comparison with the dihydroergotamine-heparin combination.
AB  - A randomized study was carried out in order to compare the low-molecular heparin
      enoxaparin to heparin-dihydroergotamine (HDHE) combination, as prophylactic anti
      thrombotic measure in patients undergoing hip replacement or knee replacement
      surgery or fractures of the femoral neck. A total of 165 patients both female and
      male were included in the study. The patients were randomized into two treatment
      groups. One group was treated with heparin-dihydroergotamine 0.5 mg + 5,000 IU
      twice a day and the other with enoxaparin 40 mg once daily. All patients were
      examined with Doppler ultrasound on day 3-5 and after the termination of
      medication which was the end of the study. Positive Doppler ultrasound findings
      were confirmed either by duplex Doppler or phlebography and clinical signs of
      pulmonary embolism were confirmed by isotope scintigraphy. The overall incidence
      of thromboembolic events was low (3%). One deep venous thrombosis (DVT) was seen
      in the enoxaparin group and two cases of pulmonary embolism in the heparin
      dihydroergotamine group. Thus, the two regimens showed comparable efficacy and
      the overall safety was comparable. However, enoxaparin caused significantly less
      injection site haematoma. Correspondingly, the size of the injection site
      haematoma was significantly smaller in the enoxaparin group.

PMID- 9014068
TI  - Reinsertion of the ruptured ulnar collateral ligament of the metacarpophalangeal
      joint of the thumb with an absorbable self-reinforced polylactide mini tack.
AB  - Total rupture of the ulnar collateral ligament of the first metacarpophalangeal
      joint is a common injury and it needs to be operated on, otherwise the injured
      joint will be unstable and it will cause disability due to loss of pinch grip. A
      special absorbable device--self-reinforced poly-L-lactide mini tack--was used to
      stabilise this ruptured ligament. 140 patients were operated on because of this
      ligament injury. The preliminary results after six months' follow-up were good.
      Normal movement was regained in 118 out of 140 patients (84.3%) and stability in
      138 patients (98.6%). Five reoperations (3.6%) were needed--one because of scar
      pain, one because of local infection nine months postoperatively, one because of
      instability and two because of late loosening of the tack six and nine months
      postoperatively. Overall the preliminary results were good. On the basis of these
      findings we consider this new absorbable fixation method suitable for clinical
      use for reinserting the ruptured ulnar collateral ligament of the first
      metacarpophalangeal joint of thumb.

PMID- 9014069
TI  - ABO blood group and Achilles tendon rupture.
AB  - The association between ABO blood groups and Achilles tendon (AT) ruptures was
      studied in 215 consecutive AT rupture patients treated at Oulu University
      Hospital during the 16-year period from 1979 to 1994 as compared with control
      material consisting of earlier blood group determinations performed on an
      unselected sample of 5,536 young Finnish male adults. There was no blood group O
      dominance or other statistical differences in ABO blood groups between the
      patients with AT rupture and the control population (chi 2 3.79, P = 0.28), the
      A/O ratio being 1.82 in the rupture group and 1.42 in the controls. We found no
      blood group O dominance in competitive athletes, recreational athletes or non
      athletes, in patients with sports-related AT ruptures or non-sports-related
      ruptures and in younger (< 45 years) or older (> or = 45--years) patients. In
      conclusion, our results do not confirm early findings of blood group O dominance
      in patients with AT rupture.

PMID- 9014130
TI  - The cerebellum: a model system for studying GABAA receptor diversity.
AB  - The basic unsolved questions concerning GABAA receptors are: "How many receptor
      subtypes exist?", "What subtypes are used by which types of neuron and where are
      they located on the cell?", and "What are the functions of the different
      subtypes?" As described in this Review, the cerebellum is an ideal vertebrate
      brain region for investigating these issues.

PMID- 9014131
TI  - Effects of neurosteroid and benz[e]indene enantiomers on GABAA receptors in
      cultured hippocampal neurons and transfected HEK-293 cells.
AB  - The effects of the enantiomers of the neurosteroid, 3 alpha-hydroxy-5 alpha
      pregnan-20-one (DHP), and the benz[e]indene, BI-1, on gamma-aminobutyric acid
      (GABA) responses were studied using whole-cell recording techniques in cultured
      rat hippocampal neurons and human embryonic kidney cells (HEK-293) transfected
      with either alpha 1 beta 2 gamma 2 or alpha 6 beta 2 gamma 2 GABAA receptor
      subunits. At 10 microM, the (+)-enantiomers enhanced currents gated by 2 microM
      GABA in all cells, whereas the (-)-enantiomers were significantly less effective.
      The enhancement of 2 microM GABA responses in HEK-293 cells transfected with
      alpha 6 beta 2 gamma 2 subunits was about half that of hippocampal neurons or HEK
      293 cells transfected with alpha 1 beta 2 gamma 2. The lower sensitivity of alpha
      6 beta 2 gamma 2 receptors for (+)-DHP and (+)-BI-1 is accounted for by their
      greater apparent affinity for GABA. When the GABA concentration was decreased to
      0.5 microM to take into account the four-fold higher apparent affinity of alpha 6
      beta 2 gamma 2 receptors, these receptors exhibited enhancement similar to alpha
      1 beta 2 gamma 2 receptors. These results indicate that both native and
      recombinant GABAA receptors have enantioselective sites at which neurosteroids
      and benz[e]indenes modulate GABA responses, and that differences in agonist
      affinity contribute to apparent differences in steroid sensitivity among GABAA
      receptors.

PMID- 9014132
TI  - Modulation of synaptic GABAA receptor function by benzodiazepines in area CA3 of
      rat hippocampal slice cultures.
AB  - The effects of the benzodiazepine agonist midazolam on GABAA receptor-mediated
      inhibition were investigated in area CA3 of hippocampal slice cultures. Midazolam
      (100 nM) increased the decay time constant (tau OFF) of miniature inhibitory
      postsynaptic currents (mIPSCs) recorded from pyramidal cells by approximately
      40%, but did not significantly affect their activation rate or amplitude,
      consistent with saturation of postsynaptic GABAA receptors by a quantum of GABA.
      Non-stationary variance analysis of mIPSCs revealed that the unitary conductance
      of synaptic GABAA channels (approximately 31 pS) was unaffected by midazolam.
      Midazolam increased not only the tau OFF (51%), but also the amplitude (23%) of
      unitary IPSPs, recorded from pairs of monosynaptically connected inhibitory and
      pyramidal cells. Simulation of unitary IPSPs indicated that the increased
      amplitude was primarily due to the slow time constant of pyramidal cells.
      Finally, the mean amplitude, tau OFF, and single-channel conductance of mIPSCs
      recorded in cultures chronically exposed to midazolam (0.1-10 microM) for 2 weeks
      were not different from control mIPSCs, nor was their response to midazolam. We
      conclude that benzodiazepines increase synaptic GABAA channel open time, as
      described previously, and that this results in an increase in both the amplitude
      and duration of IPSPs in pyramidal cells.

PMID- 9014134
TI  - Pharmacological characterisation of multiple components in the enhancement by
      pregnanolone and propofol of [3H]flunitrazepam binding to GABAA receptors.
AB  - The enhancement by pregnanolone (5 beta-pregnan-3 alpha-ol-20-one) and propofol
      (2,6-diisopropylphenol) of [3H]flunitrazepam (FNZ) binding to GABAA receptors in
      rat whole brain homogenate has been investigated. Two components in the
      concentration-effect relationship for pregnanolone were distinguished by the
      sensitivity of one component to antagonism by bicuculline and enhancement by
      muscimol, and the selective but weak antagonism of the bicuculline-insensitive
      component by 11-ketoprogesterone (4-pregnen-3,11,20-trione). Unlike pregnanolone,
      the enhancement by propofol of [3H]FNZ binding appeared to comprise a single
      component which was insensitive to 11-ketoprogesterone and was only slightly
      antagonised by bicuculline and slightly enhanced by muscimol. These results
      provide evidence for distinct GABA-dependent and GABA-independent components of
      the action of pregnanolone in the enhancement of [3H]FNZ binding, with the GABA
      independent component being sensitive to 11-ketoprogesterone. The data also
      support the suggestion of different binding sites for pregnanolone and propofol.

PMID- 9014133
TI  - Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal
      neurones to the GABAA receptor partial agonist, 4-PIOL.
AB  - We have previously characterized 5-(4-piperidyl)isoxazol-3-ol (4-PIOL) as a non
      desensitizing partial agonist at GABAA receptors and shown that the responses are
      mediated by short-duration channel openings consonant with single-ligand gated
      openings of the Cl- channels. We presently investigate whether responses of
      cultured rat hippocampal neurones to 4-PIOL are modulated by benzodiazepine (BDZ)
      and barbiturate receptor ligands. Whole-cell patch-clamp recordings of maximal
      responses to 1 mM 4-PIOL were comparable in size to responses evoked by 10 microM
      of the full GABAA agonist, isoguvacine. The BDZ receptor inverse agonist, DMCM (1
      microM) reduced responses to isoguvacine (to 65.7 +/- 11.0%) and 4-PIOL (to 69.3
      +/- 3.5%) to a similar extent. The BDZ agonist, midazolam (0.1 microM)
      potentiated responses to both agonists, and resulted in responses with an early
      peak with later fading. Potentiation of the peak response to 4-PIOL (to 163 +/-
      14%) was significantly less than for isoguvacine (215 +/- 11%). Pentobarbital (50
      microM) caused a very marked, but variable, potentiation of the peak response to
      4-PIOL (to 484 +/- 93%), which was significantly greater than the potentiation of
      the peak response to isoguvacine (to 304 +/- 46%), and induced fading. This
      suggests that a relatively larger number of the 4-PIOL-induced channel openings
      can be transformed to longer duration openings by pentobarbital. In conclusion,
      responses to 4-PIOL and isoguvacine are modulated by BDZ and barbiturate ligands
      in a qualitatively similar manner, but with a number of quantitative differences
      which cannot be readily explained by the kinetic model of Macdonald and Twyman
      (1992). Investigation of these responses at the single-channel level could
      provide further insight into the operation of the GABAA receptor-ionophore
      complex.

PMID- 9014135
TI  - Identification of domains in human recombinant GABAA receptors that are
      photoaffinity labelled by [3H]flunitrazepam and [3H]Ro15-4513.
AB  - We have used [3H]flunitrazepam and [3H]Ro15-4513 as photoaffinity labelling
      agents in combination with a chemical cleavage technique to localize the
      benzodiazepine recognition sites of specific human recombinant alpha 1 beta 1
      gamma 2, alpha 1 beta 3 gamma 2 and alpha 6 beta 3 gamma 2 GABAA receptor
      subtypes. The chemical agent utilized was hydroxylamine, whose substrate is a
      relatively rare asparagine-glycine amide bond that occurs only in the alpha
      subunits of the receptors examined in this study. Cleavage products were resolved
      using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The
      results of these experiments show that, in the alpha 1 subunit-containing
      receptors, incorporation of [3H]flunitrazepam occurs within residues 1-103 of the
      alpha 1 subunit, while incorporation of [3H]Ro15-4513 occurs within the region of
      the alpha 1 subunit that lies between residue 104 and the C-terminus.
      Photolabelling of membranes prepared from the alpha 6 beta 3 gamma 2-expressing
      cell line with [3H]Ro15-4513 resulted in the incorporation of radiolabel into two
      major protein species of M(r) 56,000 and M(r) 48,000, indicating incorporation
      into the alpha 6 subunit and possibly also the gamma 2 subunit. Hydroxylamine
      cleavage of alpha 6-containing receptors labelled with [3H]Ro15-4513 produced a
      gel profile consistent with the incorporation of the label occurring between
      residue 125 and the C-terminal. Thus, we have shown that the recognition sites
      for the agonist [3H]flunitrazepam and the inverse agonist [3H]Ro15-4513 occur
      within distinct domains of the human GABAA receptor.

PMID- 9014136
TI  - The anaesthetic action and modulation of GABAA receptor activity by the novel
      water-soluble aminosteroid Org 20599.
AB  - The anaesthetic profile of a novel water-soluble aminosteroid, Org 20599 [(2
      beta, 3 alpha, 5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one
      methanesulphonate], and the ability of the compound to allosterically regulate
      the activity of the GABAA receptor, have been studied in comparison to the
      properties of established intravenous general-anaesthetic agents. Intravenously
      administered Org 20599 produced a rapid onset, short duration loss of the
      righting reflex in mice. The anaesthetic potency of Org 20599 was comparable to
      that of the steroids 5 alpha-pregnan-3 alpha-ol-20-one or alphaxalone, and
      exceeded that of propofol, thiopentone or pentobarbitone. Org 20599 and the
      reference anaesthetic agents allosterically displaced the binding of [35S]-t
      butylbicyclophosphorothionate (TBPS) from GABAA receptors of rat-brain membranes
      with the order of potency: 5 alpha-pregnan-3 alpha-ol-20-one > Org 20599 >
      alphaxalone > propofol > thiopentone > pentobarbitone. At human recombinant alpha
      1, beta 2, gamma 2L subunit-containing GABAA receptors expressed in Xenopus
      laevis oocytes, the anaesthetic agents produced a concentration-dependent and
      reversible potentiation of the peak amplitude of GABA-evoked currents. A similar
      positive allosteric action of Org 20599 was observed for the GABAA receptors
      expressed by bovine adrenal chromaffin cells maintained in culture. The rank
      order of potency in the aforementioned assays was identical to that determined
      from the displacement of TBPS binding. At concentrations greater than those
      required for potentiation of GABA, the anaesthetics exhibited GABA-mimetic
      effects with a rank order of potency that paralleled their modulatory activity.
      Such direct agonism varied greatly in maximal effect between compounds. The
      modulatory and direct agonist actions of Org 20599 were additionally confirmed
      utilizing rat hippocampal neurones in culture. The results indicate Org 20599 to
      be a potent and short-acting intravenous anaesthetic agent in mice and suggest
      positive allosteric regulation of GABAA receptor function to be a plausible
      molecular mechanism of action for the drug.

PMID- 9014137
TI  - Modulation of human recombinant GABAA receptors by pregnanediols.
AB  - Utilising two point voltage-clamp techniques on Xenopus laevis oocytes expressing
      human (alpha 1 beta 1 gamma 2L) recombinant GABAA receptors, the GABA modulatory
      actions of six naturally occurring neurosteroids have been determined and
      compared with those of known positive allosteric modulators. The anaesthetic
      steroids 5 alpha- and 5 beta-pregnan-3 alpha-ol-20-one produced a concentration
      dependent enhancement of the GABA-evoked current. The maximal enhancement of the
      agonist-induced response produced by these steroids was intermediate between that
      of pentobarbitone and diazepam, but much greater than that caused by bretazenil.
      For both the 5 alpha and 5 beta steroid a reduction of the 20 ketone group to
      form either the corresponding 20 alpha or 20 beta hydroxy steroid produced, in
      all cases, a reduction in potency and a decrease in the maximal effect. The
      relationship of steroid structure to these two parameters is considered. The
      influence of the alpha subtype (alpha x beta 1 gamma 2L, where x = 1, 2 or 3) for
      the behaviourally active 5 alpha-pregnan-3 alpha,20 alpha-diol is also
      determined. Although the maximal effect of the steroid is not influenced by the
      alpha subtype, the alpha 2-containing receptor exhibits a modest decrease
      (approximately 6-fold) in potency compared to alpha 1- and alpha 3-containing
      receptors. The results described here are discussed in relation to the distinct
      behavioural actions of the neurosteroids.

PMID- 9014138
TI  - Loreclezole enhances apparent desensitization of recombinant GABAA receptor
      currents.
AB  - Loreclezole is a newly developed antiepileptic drug which has been shown to act
      at a specific site on beta 2 or beta 3 GABAA receptor subtypes to enhance the
      peak whole-cell response to submaximal concentrations of GABA. Potentiation by
      loreclezole occurred with high affinity only at GABAA receptors containing a beta
      2 or beta 3 subtype, not a beta 1 subtype. We have studied the effect of
      loreclezole on whole-cell currents from recombinant GABAA receptors transiently
      expressed in L929 fibroblasts and on currents from cultured mouse cortical
      neurons and have found a second, inhibitory action of loreclezole that was
      independent of the beta-subunit subtype composition of the receptor. Loreclezole,
      at concentrations above 6 microM, enhanced the degree and rate of apparent
      desensitization of the whole-cell current in a concentration-dependent manner.
      This effect was voltage-independent, non-competitive and increased with
      increasing GABA concentration. The increase in desensitization was not blocked by
      the benzodiazepine antagonist flumazenil and did not require the presence of a
      gamma subunit. Loreclezole acted at a novel inhibitory allosteric site to
      increase the apparent desensitization of the GABAA receptor, regardless of its
      subunit composition. This activity of loreclezole may have implications for its
      experimental or clinical use as an antiepileptic drug.

PMID- 9014139
TI  - A behavioural and neurochemical study in rats of the pharmacology of loreclezole,
      a novel allosteric modulator of the GABAA receptor.
AB  - Loreclezole is an anticonvulsant and anxiolytic compound which has been reported
      to potentiate GABA via a novel allosteric site on the beta-subunit of the
      receptor. We have now studied in rats both the in vivo and in vitro pharmacology
      of the compound. The dose of loreclezole required to increase by 50% the dose of
      intravenous pentylenetetrazol eliciting a seizure was comparable to that of
      barbiturates and chlormethiazole (in mg/kg): diazepam, 1.3; pentobarbitone, 16;
      chlormethiazole, 22; loreclezole, 25; pentobarbitone, 36. Loreclezole dose
      dependently decreased locomotion (dose to decrease locomotion by 50% (in mg/kg):
      chlormethiazole, 9; pentobarbitone, 16; loreclezole, 25). Loreclezole,
      chlormethiazole and pentobarbitone all failed to displace [3H]muscimol and
      [3H]flunitrazepam binding from a rat cortical membrane preparation. All three
      compounds fully displaced [35S]TBPS binding (IC50 values: loreclezole, 4.34 +/-
      0.68 microM; pentobarbitone, 37.39 +/- 3.24 microM; chlormethiazole, 82.10 +/-
      8.52 microM). Addition of bicuculline (10 microM) produced a major rightward
      shift in the loreclezole and pentobarbitone displacement curves, increasing IC50
      values for [35S]TBPS binding by 25 times (loreclezole), 6 times (pentobarbitone)
      and 2.7 times (chlormethiazole), suggesting a greater involvement of GABA in the
      interaction of loreclezole with the chloride channel than in the case of
      chlormethiazole. Anticonvulsant activity of the compounds did not appear to
      relate to [35S]TBPS binding activity. Other binding data suggested that although
      the evidence of others indicates that loreclezole interacts with a specific
      allosteric site on the beta-subunit, it nevertheless also alters the binding
      characteristics of other modulatory sites.

PMID- 9014140
TI  - Effects of the nootropic drug nefiracetam on the GABAA receptor-channel complex
      in dorsal root ganglion neurons.
AB  - The effects of nefiracetam on GABA-induced chloride currents were studied with
      rat dorsal root ganglion neurons in primary culture using the whole-cell patch
      clamp technique. The dose-response curve for GABA-induced currents was shifted by
      16 microM to lower concentrations by 10 microM nefiracetam while the maximal
      response was reduced by 22.84 +/- 0.68%. Thus at a low concentration (10 microM)
      of GABA, the chloride currents were potentiated by nefiracetam in a concentration
      dependent manner. With 10 microM nefiracetam, the potentiation occurred slowly
      and the recovery after washout was also slow. The desensitization of the GABAA
      receptor at high concentration (100 microM) of GABA was accelerated by
      nefiracetam. The recovery process of chloride currents from desensitization was
      not affected by nefiracetam. KT 5720 (0.56 microm), a specific protein kinase A
      (PKA) inhibitor, blocked the transient potentiation of GABA-activated currents by
      nefiracetam, but did not affect the acceleration of desensitization. Nefiracetam
      suppression of GABA-induced currents was also abolished by KT 5720 or the
      pertussis toxin. Thus, nefiracetam may inhibit Gi/G(o) proteins leading to a
      cascade of events that increase the intracellular cAMP level, activate the PKA
      system, and suppress GABA-induced currents. Nefiracetam-induced transient
      potentiation and acceleration of desensitization of GABA-induced currents may
      involve other pathways. The nefiracetam modulation of the GABAA receptor function
      will result in a nootropic effect on the central nervous system through
      modification of synaptic transmission.

PMID- 9014141
TI  - Inhibition of GABAA receptor chloride channel by quinolones and norfloxacin
      biphenylacetic acid hybrid compounds.
AB  - Receptor binding studies have shown that the combination of some new quinolone
      antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen,
      inhibits GABAA receptors. In order to elucidate further the mechanism of these
      drug interactions, the effect of quinolone antibacterial agents on muscimol
      stimulated 36Cl- uptake in rat cerebral cortical synaptoneurosomes was
      investigated in the absence or presence of BPAA. In the absence of BPAA,
      quinolones such as norfloxacin (NFLX) and enoxacin attenuated muscimol-stimulated
      36Cl- uptake at 10 microM and above. In combination with 10 microM BPAA, the
      inhibitory effect of these drugs was potentiated and there was a parallel shift
      of the inhibition curves to the left for these drugs. BPAA alone (1 and 10
      microM) did not affect basal or muscimol-stimulated 36Cl- uptake. Hybrid
      molecules of NFLX and BPAA were synthesized and their inhibitory potency was also
      investigated. Inhibition curves of muscimol-stimulated 36Cl- uptake revealed that
      a hybrid with a -CONH(CH2)3- chain between NFLX and BPAA (flexible structure) (1
      nM-20 microM) inhibited muscimol-stimulated 36Cl- uptake more potently than did
      the combination of NFLX (10 nm-100 microM) and 10 microM BPAA. In contrast,
      another hybrid linked by -CONH-(stretched structure) exhibited a weak inhibitory
      effect at 10 microM. These results suggest that quinolones in combination with
      BPAA bind to GABAA receptors, thus inhibiting Cl- channel activity, and that the
      inhibitory potency of quinolones may be enhanced by an intermolecular interaction
      with BPAA.

PMID- 9014142
TI  - Evidence that a hybrid molecule of norfloxacin and biphenylacetic acid is a
      potent antagonist at the GABAA receptor.
AB  - The combination of some fluorinated quinolone antimicrobials and certain non
      steroidal anti-inflammatory drugs (NSAIDs), such as fenbufen, has been reported
      to elicit serious convulsions in humans. Fluoroquinolones, including norfloxacin
      (NFLX) and NSAIDs synergistically inhibit GABAA receptors. The mechanism(s) of
      the synergism, however, at present remains unclear. In the present study, the
      hypothesis that NFLX and biphenylacetic acid (BPA), an active metabolite of
      fenbufen, undergo an intermolecular interaction to produce a more potent GABAA
      antagonist, was investigated by examining the effects of two hybrid molecules of
      NFLX linked with BPA on GABA-evoked whole cell currents, recorded from rat
      hippocampal neurons using the perforated-patch clamp technique. Hybrid-1, with a 
      CONH(CH2)3- chain between NFLX and BPA, inhibited the GABA response more potently
      than co-treatment with NFLX and BPA. In contrast, hybrid-2 with a -CONH- chain
      between NFLX and BPA, exhibited only a weak inhibition of the GABA response. The
      characterization of the inhibition of the GABA response in the presence of hybrid
      1 was similar to that of the combination of NFLX and BPA regarding the following:
      (1) there was a rightward parallel shift of the concentration-response curve of
      GABA at lower concentrations and a suppression of the maximal response to GABA at
      higher concentrations; (2) it was voltage-independent; and (3) there was no
      influence on the reversal potential of the GABA response. These results therefore
      suggest that NFLX and BPA interact with the GABAA receptor at nearby sites and
      thus suppress the GABA response.

PMID- 9014143
TI  - Proton modulation of functionally distinct GABAA receptors in acutely isolated
      pyramidal neurons of rat hippocampus.
AB  - We have studied the effect of extracellular pH (pHo) on the GABAA receptor
      mediated chloride conductance in acutely isolated pyramidal neurons from area CA1
      of the rat hippocampus under whole-cell voltage clamp in bicarbonate-free
      solutions. The conductance evoked by saturating or near-saturating concentrations
      (200-1000 microM) of GABA showed a marked sensitivity to variations of pHo around
      7.4. A decrease in pHo between 8.4 and 6.4 increased the GABAA receptor-mediated
      chloride conductance by about two-fold per pH unit. In contrast, when evoked by a
      low agonist concentration (1-10 microM) the conductance showed an equally marked
      decrease upon a decrease in pHo. The half-time for desensitization of the
      conductance induced by 500 microM GABA was around 900 ms at pHo 6.4 and 7.4, but
      decreased to 650 ms at pHo 8.4. A fall in pHo decreased the amount of
      desensitization of the conductance evoked by a 5 s application of 5 microM, but
      not of 500 microM, GABA. The concentration-response relationship of the GABA
      induced conductance showed a local plateau between 50 and 100 microM of GABA,
      which was particularly evident at high pHo. Assuming two receptor populations
      with a high and a low affinity for GABA, the effect of H+ on the GABAA receptors
      could be explained as an increase in the EC50 of the high affinity receptor, and
      an apparently non-competitive potentiation of both the high and the low affinity
      receptors. The GABAA receptor-mediated conductance was markedly inhibited by 20
      50 microM Zn2+. In addition, Zn2+ reverted the down-modulation by H+ observed at
      low GABA concentrations to up-modulation. Diazepam (1-10 microM) had only a
      marginal effect on the GABA-gated conductance. Taken together, the results
      suggest the coexistence in individual hippocampal neurons of two distinct GABAA
      receptor populations having differential sensitivities to H+. In the light of the
      inhibitory action of Zn2+ and the virtual absence of an effect of diazepam it is
      probable that a significant fraction of the GABAA receptors lack the gamma 2
      subunit. The observation that an elevated pH has a strong suppressing effect on
      the conductance evoked by high concentrations of GABA may at least partly explain
      why an extracellular alkalosis leads to neuronal hyperexcitability.

PMID- 9014144
TI  - A functional comparison of the antagonists bicuculline and picrotoxin at
      recombinant GABAA receptors.
AB  - Allosteric modulation of GABAA receptor function by a number of ligands has been
      shown to be dependent on the subunit composition of the receptor complex. In this
      respect, modulation of GABAA receptors by the antagonists bicuculline and
      picrotoxin was examined in Xenopus laevis oocytes expressing recombinant GABAA
      receptors composed of combinations of murine alpha 1, beta 1, gamma 2S and gamma
      2L subunits. Bicuculline and picrotoxin reduced GABA-activated responses mediated
      by GABAA receptors composed of alpha 1 beta 1, alpha 1 beta 1 gamma 2S and alpha
      1 beta 1 gamma 2L subunits in a dose-dependent manner. GABA equilibrium
      concentration-response curves for each receptor construct were shifted to the
      right by increasing concentrations of bicuculline in a competitive manner,
      whereas picrotoxin induced a slight lateral shift as well as a depression of the
      maximum response consistent with a mixed/non-competitive inhibitory mechanism.
      GABA concentration-response curves in the absence and presence of bicuculline
      were subjected to Schild analysis, which revealed similar pKB values of
      approximately 5.9 for alpha 1 beta 1, alpha 1 beta 1 gamma 2S and alpha 1 beta 1
      gamma 2L receptor constructs. Concentration inhibition curves were used to
      estimate IC50 for picrotoxin were relatively unaffected by the GABAA receptor
      isoforms used in this study, and in particular, by the absence of the gamma 2
      subunit in the alpha 1 beta 1 GABAA receptor complex. The similarity of the pKBs
      reported in this study to those previously reported using native neuronal
      preparations, which are likely to represent heterogeneous GABAA receptor
      populations, further indicates the lack of dependence on receptor subunit
      composition for the inhibitory action of bicuculline.

PMID- 9014146
TI  - Pharmacological properties of recombinant "diazepam-insensitive" GABAA receptors.
AB  - Both native and recombinant "diazepam-insensitive" GABAA receptors (DI) are
      characterized by the very low affinities of prototypic 1,4-benzodiazepines such
      as diazepam and the high affinity of an imidazobenzodiazepine, Ro 15-4513. The
      presence of either an alpha 4 or alpha 6 subunit imparts this unusual
      pharmacological profile to DI. Based on the affinities of these compounds at
      recombinant DI, the pharmacological properties of alpha 4- and alpha 6-bearing
      receptor isoforms appear to be very similar if not identical. Using a larger
      sample of structurally diverse compounds, we now demonstrate distinct but related
      ligand binding profiles of recombinant alpha 4 beta 2 gamma 2 and alpha 6 beta 2
      gamma 2 DI. Comparison of 18 ligands drawn from three principal structural groups
      (beta-carbolines, imidazobenzodiazepines and pyrazoloquinolinones) revealed that
      the affinity of at least one representative from each group differed by > 5-fold
      between alpha 4- and alpha 6 beta 2 gamma 2 receptors. While the high correlation
      (r2 = 0.926; p < 0.001) obtained between the affinities of these ligands at alpha
      4- and alpha 6-containing receptors underscores the similarity between these
      receptor isoforms, a significant deviation of the slope of this correlation
      (0.792; 95% C.I. 0.673-0.911) from unity is substantive evidence that these DI
      possess distinct pharmacological profiles. These findings indicate that it is
      feasible to develop selective ligands for these DI isoforms.

PMID- 9014145
TI  - Isoniazid-induced inhibition of GABAergic transmission enhances neurosteroid
      content in the rat brain.
AB  - Isoniazid (375 mg/kg, s.c.), a drug that decreases GABAA receptor-mediated
      transmission, elicited a time-dependent increase of neuroactive steroid
      (pregnenolone, progesterone and allotetrahydrodeoxycorticosterone) concentrations
      in rat brain and plasma. This treatment also time-dependently increased the
      plasma concentration of corticosterone. Brain and plasma neuroactive steroid
      levels peaked between 40 and 120 min after isoniazid administration,
      respectively, and returned to control values by 5 hr. Acute foot shock stress
      mimicked the effect of isoniazid by increasing in a time-dependent manner the
      same neuroactive steroids both in brain and plasma. Abecarnil (0.3 mg/kg, i.p.),
      a beta-carboline derivative with anxiolytic properties, antagonized the effect of
      both isoniazid and foot shock on brain and plasma neuroactive steroids and on
      plasma corticosterone level. These data indicate that an inhibition of central
      GABAergic transmission enhances the concentrations of THDOC and its precursors
      pregnenolone and progesterone in the rat brain and plasma as well as the plasma
      levels of corticosterone. This finding suggests that GABA exerts a tonic
      inhibitory action on the mechanisms involved in the regulation of the synthesis
      and release of these neuroactive steroids in the central nervous system and
      plasma.

PMID- 9014147
TI  - The alpha 4 subunit of the GABAA receptors from rat brain and retina.
AB  - A novel anti-alpha 4 antibody has been used for the purification and
      characterization of the alpha 4-containing GABAA receptors in the rat brain and
      for studying the immunocytochemical distribution of the alpha 4 subunit peptide
      in rat brain and retina. The anti-alpha 4 antibody recognized a 66 kDa peptide in
      brain membranes and immunoprecipitated 10-28% of the brain GABAA receptors in
      various brain regions as determined by [3H]muscimol binding. The highest
      immunoprecipitation values were obtained in the thalamus and the lowest in the
      cerebellum. Surprisingly, the receptors immunoprecipitated by anti-alpha 4 showed
      little or no diazepam-insensitive or diazepam-sensitive [3H]Ro15-4513 binding
      sites in any brain region. In the cerebellum, where 25% of the [3H]Ro15-4513
      binding is diazepam-insensitive, much of the latter was immunoprecipitated by an
      anti-alpha 6 antibody but not by the anti-alpha 4 antibody. Immunoblots of
      immunoaffinity-purified GABAA receptors from the cerebral cortex on immobilized
      anti-alpha 4 revealed molecular colocalization of alpha 4 and gamma 2. However,
      the absence of significant benzodiazepine binding in these GABAA receptors
      suggests that the assembly of the alpha 4 and gamma 2 subunits in the cerebral
      cortex and in other brain regions is such that they do not normally form diazepam
      insensitive [3H]Ro15-4513 binding sites. This result contrasts with the presence
      of diazepam-insensitive [3H]Ro15-4513 binding sites in the GABAA receptors
      expressed in heterologous systems resulting from the combination of alpha 4,
      gamma 2 and beta 2 subunits. Immunocytochemistry has revealed the abundance of
      alpha 4 peptide immunoreactivity in the thalamus and dentate gyrus (mainly in the
      hilar neurons and the inner third of the granule cell layer). The alpha 4
      immunoreactivity is also present in the external plexiform layer of the olfactory
      bulb and in all layers of the neocortex and pyriform cortex. In the retina, alpha
      4 is concentrated on ganglion cells (including some giant ganglion cells), the
      inner plexiform layer and to a lesser extent in the outer plexiform layer.

PMID- 9014148
TI  - Extensive heterogeneity of recombinant gamma-aminobutyric acidA receptors
      expressed in alpha 4 beta 3 gamma 2-transfected human embryonic kidney 293 cells.
AB  - Human embryonic kidney 293 cells transiently transfected with alpha 4-, beta 3-
      and gamma 2-subunits of gamma-aminobutyric acidA (GABAA) receptors from the rat
      exhibited specific high affinity binding sites for [3H]muscimol, [3H]Ro 15-4513
      and [35S]t-butylbicyclophosphorothionate (TBPS). Bmax values obtained, however,
      were dramatically different for these compounds. In addition, GABA was able to
      inhibit only 20% of specific [35S]TBPS binding to membranes from alpha 4 beta 3
      gamma 2-transfected cells. In order to investigate possible receptor
      heterogeneity, receptors were extracted from alpha 4 beta 3 gamma 2-transfected
      cells and were fractionated by chromatography on an anti-gamma 2-, followed by an
      anti-alpha 4- and an anti-beta 3-immunoaffinity column. Western blot analysis of
      the column eluates indicated the separate existence of GABAA receptors consisting
      of alpha 4 beta 3 gamma 2-, alpha 4 beta 3- or beta 3-subunits in alpha 4 beta 3
      gamma 2-transfected cells. This, and the finding that only alpha 4 beta 3 gamma 2
      but not alpha 4 beta 3- or beta 3-receptors possess high affinity binding sites
      for all three radiolabeled ligands investigated, combined with the observation
      that [35S]TBPS binding to receptors consisting of beta 3-subunits cannot be
      inhibited by GABA, can explain most of the binding data obtained. The present
      results suggest an inefficient assembly of gamma 2- with alpha 4- and/or beta 3
      subunits under the conditions used, and indicate that recombinant receptors
      expressed in HEK cells are not necessarily homogeneous.

PMID- 9014149
TI  - [3H]L-655,708, a novel ligand selective for the benzodiazepine site of GABAA
      receptors which contain the alpha 5 subunit.
AB  - A compound (L-655,708) has been identified which has at least 50-fold selectivity
      for the benzodiazepine site on GABAA receptors containing an alpha 5 subunit over
      those containing an alpha 1, alpha 2, alpha 3 or alpha 6 subunit in combination
      with beta 3 and gamma 2. The compound was radiolabelled with tritium and
      investigated as a novel radioligand which recognizes the benzodiazepine site of
      GABAA receptors which contain the alpha 5 subunit. [3H]L-655,708 labels one
      saturable and specific population of binding sites in rat hippocampus with a Kd
      of 2.4 +/- 0.7 nM and a Bmax of 256 +/- 42 fmol/mg protein. The pharmacology of
      the binding site labelled was consistent with that of receptors present in cells
      transfected with alpha 5, beta 2 and gamma 2 and with receptors
      immunoprecipitated from rat brain with an alpha 5-selective antiserum. It is
      concluded that [3H]L-655,708 is the first radioligand to date which is selective
      for any BZ2 subtype of the GABAA receptor and should provide a valuable tool for
      elucidating the structure and function of the alpha 5-containing GABAA receptor
      subtype.

PMID- 9014150
TI  - Developmental regulation of expression of GABAA receptor alpha 1 and alpha 6
      subunits in cultured rat cerebellar granule cells.
AB  - We have studied the postnatal development of GABAA receptor alpha 1 and alpha 6
      subunits expressed by primary cultures of cerebellar granule cells originating
      from 2-day-old (postnatal day 2, P2) and 10-day-old (P10) rat neonates. At these
      ages, the granule cells are at distinct stages of cerebellar development. In both
      cases, GABAA receptor alpha 1 and alpha 6 subunit-like immunoreactivities were
      detected, and displayed temporal expression profiles that were correlated with
      the maturity of the cerebella from which the cultured granule cells were derived.
      Using two different specificity anti-alpha 1 subunit-specific antibodies,
      immunoreactive species with M(r) 53,000 Da and 54,000 Da were detected by
      immunoblotting. The lower 53,000-Da band co-migrated with the alpha 1 subunit
      like immunoreactivity detected in GABAA receptors purified from adult rat
      forebrain by benzodiazepine affinity chromatography. This 53,000-Da alpha 1
      subunit-like immunoreactive species was detected at day 1 in vitro (1 DIV) in P10
      cultures and 3-5 DIV in P2 cultures. The GABAA receptor alpha 6 subunit-like
      immunoreactivity (58,000 Da) was not detected until 5-7 DIV in P10 and 9-11 DIV
      in P2-derived cultures. The appearance of alpha 6 subunit-like immunoreactivity
      was paralleled by an up-regulation of alpha 1 subunit expression and a
      concomitant increase in diazepam-insensitive (DZ-IS) [3H]Ro 15-4513 binding
      activity, a pharmacological characteristic of alpha 6 and alpha 1 alpha 6-subunit
      containing GABAA receptors (Pollard et al. J. Biol. Chem., 270, 21,285-21,290,
      (1995)). Antagonism of both non-NMDA and NMDA subtypes of ionotropic glutamate
      receptors did not significantly affect the developmental profile, the level of
      GABAA receptor alpha 6 subunit or the total DZ-IS or DZ-S [3H]Ro 15-4513 binding
      activities expressed by these neurons. These results provide further evidence
      that the expression of specific GABAA receptor subunit genes is subject to
      differential regulation. Furthermore, developmental expression of the GABAA
      receptor alpha 6 subunit gene by these neurons is either a preprogrammed event or
      is initiated by an environmental cue that is received early in granule cell
      development, and it is not a result of afferent activation of ionotropic
      glutamate receptors.

PMID- 9014151
TI  - Inhibition of GABA-gated chloride channels in brain by the arachidonic acid
      metabolite, thromboxane A2.
AB  - Previously, we showed that arachidonic acid and prostaglandin metabolites
      inhibited GABAA responses in rat cerebral cortex. Thromboxane A2 (TXA2), a
      metabolite of arachidonic acid, has potent actions on blood vessels and
      platelets, but its actions on neurons are not known. Here, we examined the
      effects of several TXA2 analogs on the functional and binding characteristics of
      GABAA receptors in rat brain. The stable analogs of TXA2, pinane and carbocyclic
      TXA2, and the TXA2 agonist, U-46619, inhibited muscimol-induced 36Cl- uptake in
      cerebral cortical synaptoneurosomes. Carbocyclic TXA2 decreased the maximal
      response to muscimol, consistent with a non-competitive interaction. The TXA2
      antagonist, SQ 25,548, did not block the effects of either arachidonic acid or
      carbocyclic TXA2. Neither the biologically inactive metabolite of TXA2, TXB2, nor
      carbacyclin, a stable analog of prostacyclin (prostaglandin I2) had an effect on
      GABAA responses. Thus the pharmacology differs from that in vascular smooth
      muscle and platelets. To determine if GABAA receptors were sensitive to the
      thromboxanes, the effect of pinane TXA2 on the binding of [35S]t
      butylbicyclophosphorothionate ([35S]TBPS) to GABA-gated Cl- channels was measured
      using receptor autoradiography. Pinane TXA2 inhibited [35S]TBPS binding in a
      regionally selective and non-competitive manner; the greatest inhibition was in
      the cerebral cortex, hippocampus and striatum, areas which are selectively
      vulnerable to cerebral ischemia. We conclude that TXA2 can interact with neuronal
      membranes to inhibit GABA receptor function, independent of its actions on the
      cerebrovasculature and on glial cells. This may be important during pathologic
      states such as ischemia, when TXA2 accumulates in extracellular spaces.

PMID- 9014152
TI  - Modulation of GABAA receptor function by G protein-coupled 5-HT2C receptors.
AB  - Two classical neurotransmitters, 5-hydroxytryptamine (5-HT) and GABA, coexist in
      neurons of the medulla oblongata, and activation of 5-HT receptors modulates
      GABAA receptor function in neurons of the ventral tegmental area, substantia
      nigra and cerebellum. We now report that activation of 5-HT2C receptors produces
      a long-lasting (20-90 min) inhibition of GABAA receptors in Xenopus oocytes
      coexpressing both types of receptors 5-HT2C receptors caused a approximately 60%
      decrease in the GABAA receptor Emax without affecting the EC50 or Hill
      coefficient. Intracellular microinjection of 500 microM BAPTA blocked, whereas
      microinjection of inositol 1,4,5-triphosphate mimicked the inhibitory action of 5
      HT2C receptors. The inhibition was independent of the GABAA receptors subunit
      composition; receptors containing alpha 2 beta 1, alpha 1 beta 1 gamma 2L, and
      alpha 2 beta 1 gamma 2S were inhibited to the same extent by 5-HT2C receptor
      activation. Moreover, GABAA receptors composed of wild-type alpha 2 plus mutant
      beta 1(S409A) subunits were inhibited to the same extent as wild-type receptors.
      The nonspecific protein kinase inhibitor, staurosporine, and the inhibitor of
      serine/threonine protein phosphatases, calyculin A, did not block the inhibitory
      effects of 5-HT2C receptors. The results with these inhibitors, taken together
      with those obtained with GABAA receptors with different subunit compositions,
      suggest that protein kinases or serine/threonine phosphatases are not involved in
      this GABAA receptor modulatory process. Thus, we propose that 5-HT2C receptors
      inhibit GABAA receptors by a Ca(2+)-dependent, but phosphorylation independent,
      mechanism and that 5-HT and GABA may act as cotransmitters to regulate neuronal
      activity. Furthermore, disruption of the cross-talk between these receptors may
      play a role in the anti-anxiety actions of 5-HT2 receptor antagonists.

PMID- 9014153
TI  - The effects of raising intracellular calcium on synaptic GABAA receptor-channels.
AB  - The effects of various calcium (Ca2+) loads imposed through whole-cell patch
      electrodes on dentate gyrus granule cells were investigated on synaptic GABAA
      receptor-channels. The kinetics of spontaneous inhibitory postsynaptic currents
      (sIPSCs) were similar when recorded without any exogenous Ca2+ buffers in the
      patch electrode or with up to 30 mM BAPTA in the pipette. Unbuffered Ca2+
      concentrations of 20-100 microM in the patch pipettes induced a gradual
      prolongation of miniature IPSC (mIPSC) decays over the course of the recording
      (10-40 min) with no apparent change in their rise times, peak amplitudes, or
      frequency of occurrence. This effect was not mimicked by other divalent cations
      such as strontium. Infusion into the cells of free ionic Ca2+ concentrations
      buffered with various affinity chelators in the pipette had more pronounced
      effects on synaptic GABAA currents. Free ionic Ca2+ buffered in the range of 200
      400 nM with BAPTA prolonged the decay time constant of mIPSCs. Introducing
      buffered Ca2+ into the neurons in excess of 1 microM, with a relatively low
      affinity buffer such as Br2BAPTA, resulted in a marked inhibition of mIPSCs. A
      similar effect was observed following release of Ca2+ from intracellular stores
      induced by caffeine (10 mM). We conclude that Ca2+ has a biphasic effect on
      synaptic GABAA receptor-channels. A high affinity potentiation, consistent with a
      prolongation of channel burst duration, and a low affinity depression of channel
      activity both contribute to a complex regulation of synaptic GABAA receptors by
      [Ca2+]i that has a profound bearing on cellular mechanisms of plasticity and
      pathological alterations in neuronal excitability.

PMID- 9014154
TI  - Distinct deactivation and desensitization kinetics of recombinant GABAA
      receptors.
AB  - The functional role of the large heterogeneity in GABAA receptor subunit genes
      and its role in setting the properties of inhibitory synapses in the CNS is
      poorly understood. A kinetic comparison between currents elicited by ultra-rapid
      application with a piezoelectric translator of 1 mM GABA to mammalian cells
      transfected with cDNAs encoding distinct GABAA receptor subunits revealed that
      the intrinsic deactivation and desensitization properties depend on subunit
      combination. In particular, receptors containing alpha 6 with beta 2 gamma 2
      subunits were endowed with a significantly slower deactivation as compared to
      those receptors containing alpha 1 with beta 2 gamma 2 subunits. While
      desensitization produced by prolonged GABA applications on alpha 1 beta 2 gamma 2
      receptors was characterized by a rapid exponential decay followed by a slower
      decay and a steady state response, alpha 6 beta 2 gamma 2 receptors lacked
      desensitization. Furthermore, GABAA receptors lacking the gamma 2 subunit were
      characterized by a much larger non-desensitization component and a very rapid
      deactivation. Lastly, analysis of GABA-activated currents in cells cotransfected
      with alpha 1 and alpha 6 together with beta 2 gamma 2 subunit revealed unique
      kinetic properties. Our results suggest that distinct subunit composition confers
      specific deactivation and desensitization properties that may profoundly affect
      synaptic decay kinetics and the capability to sustain high frequency synaptic
      inputs.

PMID- 9014155
TI  - Direct evidence for diazepam modulation of GABAA receptor microscopic affinity.
AB  - Alteration of agonist affinity is a potential mechanism for pharmacological
      modulation of ligand-gated receptor channel function. The time course for
      receptor activation and current onset is determined by the combined rates for two
      kinetic transitions that underlie the protein confirmations for binding agonist
      and channel gating. Using ultrafast ligand exchange techniques, we distinguish
      between these previously difficult to separate events and demonstrate their
      independent pharmacological modulation. Diazepam, which increases apparent
      affinity of gamma-aminobutyric acid (GABA) to GABAA receptors, was used to
      examine its effects on GABA binding and ion channel gating of expressed alpha 2
      beta 1 gamma 2 receptors from excised outside-out patches of acutely transfected
      HEK 293 cells. Diazepam increased rates of current onset evoked by low
      concentrations (< 1 mM) but not at saturating GABA concentrations. Furthermore,
      rates of current decay were not affected during brief applications of GABA, and
      thus, demonstrated a diazepam specific effect on ligand binding affinity and not
      channel gating kinetics. However, current decay during and following prolonged
      GABA applications were altered by diazepam in a fashion similar to that for
      higher concentrations of GABA which also increased receptor desensitization.
      These findings and analysis by computer modeling indicated that diazepam likely
      enhances GABA receptor currents primarily by accelerating GABA association to its
      receptor at the first agonist binding site. These results provide the first
      direct physiological evidence for pharmacological modulation of microscopic
      binding affinity of GABA receptors.

PMID- 9014156
TI  - Wild-type and insecticide-resistant homo-oligomeric GABA receptors of Drosophila
      melanogaster stably expressed in a Drosophila cell line.
AB  - RDL is an ionotropic GABA receptor subunit, a product of the Rdl gene, originally
      identified in the Maryland strain of Drosophila melanogaster. Here, we report the
      generation of a Drosophila melanogaster cell line (S2-RDLA302S) stably expressing
      a mutated, dieldrin-resistant (A302S) form of RDL. The properties of this
      dieldrin-resistant, homo-oligomeric receptor have been compared with those of the
      stably expressed, wild-type form (S2-RDL). Using these stable lines, a striking
      reduction in sensitivity to both picrotoxinin and dieldrin was observed for
      responses to GABA of S2-RDLA302S compared to S2-RDL. To determine if these stable
      insect cell lines generate results similar to those obtained by transient
      expression in Xenopus laevis oocytes, we have examined the actions of two widely
      used convulsants, EBOB and TBPS, and a recently developed convulsant BIDN, on RDL
      mediated GABA responses in the two expression systems. In both oocytes and S2
      cells, the three convulsants suppressed the amplitude of responses to GABA. Thus,
      in accord with earlier work on agonist and allosteric sites, the S2-RDL cell line
      is found to yield similar pharmacological results to those obtained in transient
      expression studies. Stable cell lines are now available expressing susceptible
      and resistant forms of an ionotropic receptor by GABAergic insecticides.

PMID- 9014157
TI  - Subunit stoichiometry of oligomeric membrane proteins: GABAA receptors isolated
      by selective immunoprecipitation from the cell surface.
AB  - GABAA receptors are hetero-oligomeric proteins of unknown subunit stoichiometry.
      In this study alpha 1 beta 3 GABAA receptor channels were functionally expressed
      in Xenopus oocytes. Direct immunoprecipitation from the oocyte surface was used
      to exclusively isolate mature GABAA receptors. The subunit ratio was determined
      by quantitation of the amount of [35S]methionine incorporated into individual
      receptor subunits. Antibody released from the antigen or antibody not reacted was
      prevented from reassociation with labeled antigen by addition of excess unlabeled
      antigen. Variation of the alpha 1 beta 3 ratio of injected cRNAs only slightly
      affected the subunit ratio in mature receptors. This indicates that the subunit
      stoichiometry generated is independent of the pools of newly synthesized subunit
      monomers and supports the view that the receptor assembly is a regulated process.
      The ratio of alpha 1/beta 3 subunits was found to be 1.1 +/- 0.1 (SEM, n = 6).
      Our data are in best agreement with a tetrameric receptor with the composition 2
      alpha 2 beta. For a pentameric receptor the ratio found slightly favors a
      receptor with the composition 3 alpha 2 beta. The method developed here is
      applicable to the determination of the subunit stoichiometry of other recombinant
      oligomeric membrane proteins.

PMID- 9014158
TI  - GABAA receptor subtypes differentiated by their gamma-subunit variants:
      prevalence, pharmacology and subunit architecture.
AB  - Native GABAA receptors containing different gamma-subunit variants were
      distinguished immunobiochemically with antisera selectively recognizing the gamma
      1-, gamma 2- and gamma 3-subunits. While GABAA receptors containing the gamma 2
      subunits were confirmed to be rather ubiquitous in the adult brain, receptors
      characterized by the gamma 1- or gamma 3-subunit were of low abundance, as shown
      by immunoprecipitation. The three receptor populations differed strikingly in
      their benzodiazepine (BZ) site ligand binding profiles. The gamma 3-receptor
      population displayed reduced affinity for the full agonists clonazepam
      flunitrazepam and virtually lacked sensitivity to zolpidem. The gamma 1-receptor
      population displayed low affinity for all benzodiazepine site ligands tested,
      except for flunitrazepam, and could be differentiated from the gamma 2- and gamma
      3-receptors by its low affinity for the inverse agonist beta CCM and its lack of
      affinity for the partial inverse agonist Ro 15-4513 and the antagonist
      flumazenil. Since flumazenil antagonizes all major effects of BZ agonists, gamma
      1-receptors are not involved in mediating these actions in vivo. In
      immunopurified receptors, the gamma-subunit variants were found to be assembled
      with different variants of alpha- and beta-subunits, indicating that not only the
      gamma 2-subunit gamma 1- and gamma 3-subunits are part of various receptor
      subtypes. In addition, the gamma 2- and gamma 3-subunits can be co-assembled in
      native receptors, consistent with the subunit stoichiometry of two alpha-, one
      beta- and two gamma-subunits proposed previously for recombinant receptors.

PMID- 9014159
TI  - The gamma 2 subunit of the GABAA receptor is concentrated in synaptic junctions
      containing the alpha 1 and beta 2/3 subunits in hippocampus, cerebellum and
      globus pallidus.
AB  - The gamma 2 subunit is necessary for the expression of the full benzodiazepine
      pharmacology of GABAA receptors and is one of the major subunits in the brain. In
      order to determine the location of channels containing the gamma 2 subunit in
      relation to GABA-releasing terminals on the surface of neurons, a new polyclonal
      antipeptide antiserum was developed to the gamma 2 subunit and used in high
      resolution, postembedding, immunoelectron-microscopic procedures. Dual immunogold
      labelling of the same section for two subunits, and up to three sections of the
      same synapse reacted for different subunits, were used to characterize the
      subunit composition of synaptic receptors. The gamma 2 subunit was present in
      type 2, "symmetrical" synapses in each of the brain areas studied, with the
      exception of the granule cell layer of the cerebellum. The gamma 2 subunit was
      frequently co-localized in the same synaptic junction with the alpha 1 and beta
      2/3 subunits. The immunolabelling of synapses was coincident with the junctional
      membrane specialization of the active zone. Immunolabelling for the receptor
      often occurred in multiple clusters in the synapses. In the hippocampus, the
      gamma 2 subunit was present in basket cell synapses on the somata and proximal
      dendrites and in axo-axonic cell synapses on the axon initial segment of
      pyramidal and granule cells. Some synapses on the dendrites of GABAergic
      interneurones were densely labelled for the gamma 2, alpha 1 and beta 2/3
      subunits. In the cerebellum, the gamma 2 subunit was present in both distal and
      proximal Purkinje cell dendritic synapses established by stellate and basket
      cell, respectively. On the soma of Purkinje cells, basket cell synapses were only
      weakly labelled. Synapses on interneuron dendrites were more densely labelled for
      the gamma 2, alpha 1 and beta 2/3 subunits than synapses on Purkinje or granule
      cells. Although immunoperoxidase and immunofluorescence methods show an abundance
      of the gamma 2 subunit in granule cells, the labelling of Golgi synapses was much
      weaker with the immunogold method than that of the other cell types. In the
      globus pallidus, many type 2 synapses were labelled for the gamma 2 subunit
      together with alpha 1 and beta 2/3 subunits. The results show that gamma 2 and
      beta 2/3 subunits receptor channels are highly concentrated in GABAergic synapses
      that also contain the alpha 1 and beta 2/3 subunits. Channels containing the
      gamma 2 subunit are expressed in synapses on functionally distinct domains of the
      same neuron receiving GABA from different presynaptic sources. There are
      quantitative differences in the density of GABAA receptors at synapses on
      different cell types in the same brain area.

PMID- 9014160
TI  - Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology.
AB  - GABAA and glycine receptors are close relatives in the "gene superfamily" of
      ligand-gated ion channels, but have distinctly different pharmacology. For
      example, barbiturates have two effects on GABAA receptors (GABAA-R): at low
      micromolar concentrations (2-5 microM), the anesthetic barbiturate methohexital
      potentiates submaximal chloride current responses to GABA; at higher
      concentrations (20-50 microM), the barbiturate causes direct gating of the
      channel in the absence of agonist. Neither of these barbiturate effects is seen
      on the glycine receptor (Gly-R). In order to study the structural parts of the
      GABAA-R involved in this barbiturate pharmacology, two unique restriction sites
      were introduced into the cDNAs encoding the alpha 2 and beta 1 subunits of the
      human GABAA-R and the alpha 1 subunit of the human gly-R. The first site ('X')
      corresponded to the C-terminal end of the third transmembrane domain (M3) in each
      subunit and enabled exchange of C-terminal fragment of approximately 100 amino
      acids (which includes the large 'cytoplasmic loop' and M4 segment) between GABAA
      R and Gly-R subunits. The second site ('S') was approximately 30 amino acids 3'-
      from the N-terminal end of each subunit and enabled exchange of a small N
      terminal fragment between GABAA-R and Gly-R subunits. Several chimeric receptor
      subunit cDNAs were constructed and the resulting receptors tested for their
      ability to respond to GABA and glycine and for sensitivity to the barbiturate
      methohextial (MTX). The results show that neither the large C-terminal fragment
      nor the smaller N-terminal fragment is associated with the enhancement or direct
      activation of the GABAA-R by MTX. These results demonstrate the viability of
      chimeric GABAA/Gly-R and suggest that the method will be suitable for further
      investigation of the molecular basis of the barbiturate pharmacology of the GABA
      R.

PMID- 9014161
TI  - Chronic treatment with diazepam or abecarnil differently affects the expression
      of GABAA receptor subunit mRNAs in the rat cortex.
AB  - Diazepam and abecarnil produce their overt effects by interaction with the GABAA
      receptor. Chronic treatment with abecarnil, however, does not induce diazepam
      like tolerance. This study investigates the effects of chronic diazepam and
      abecarnil treatment on expression of GABAA receptor alpha 1-6 beta 1-3 and gamma
      1-3 subunit isoform mRNAs in rat cortex. Male Sprague-Dawley rats were injected
      subcutaneously once daily for 7 or 14 days with 15 mg/kg diazepam or 6 mg/kg
      abecarnil in sesame-oil vehicle, and steady-state levels of GABAA receptor
      subunit mRNAs were quantified by solution hybridization. The levels of alpha 4-
      and alpha-, beta 1- and gamma 3-subunit mRNAs were significantly increased after
      7 days of diazepam treatment, and this effect was maintained at 14 days. A
      significant increase in alpha 3-subunit mRNA was apparent only after 14 days of
      diazepam treatment and a significant decrease in beta 2-subunit mRNA was seen
      only after 14 days of abecarnil treatment. Gamma 2-Subunit mRNA was significantly
      decreased after 14 days of either diazepam or abecarnil exposure. A degree of
      association between a particular drug treatment and changes in the levels of
      mRNAs arising from a given gene cluster was noted. Our results are consistent
      with a model of diazepam dependence based on GABAA receptor subunit isoform
      switching.

PMID- 9014162
TI  - Reversible modification of GABAA receptor subunit mRNA expression during
      tolerance to diazepam-induced cognition dysfunction.
AB  - Benzodiazepines (BZs) that are endowed with full positive allosteric modulatory
      (FAM) activity on GABAA receptors cause anterograde amnesia in both animals and
      humans. In rats subjected to a delayed object recognition test, diazepam, endowed
      with FAM activity, exerted an amnesic action, whereas BZs endowed with partial
      allosteric modulatory (PAM) activity on GABAA receptors, such as imidazenil,
      failed to induce amnesia, even if administered at doses five times higher than
      those equipotent to a standard anticonvulsant dose of diazepam (17.6
      mumol/kg/os). After discontinuation of 14 days' treatment with vehicle, diazepam,
      or imidazenil (three times daily with increasing doses starting from 17.6
      mumol/kg/os for diazepam and 2.5 mumol/kg/os for imidazenil), we compared the
      persistence of tolerance to the amnesic effect of diazepam with the persistence
      of the changes in the context of four (alpha 1, alpha 5, gamma 2L, gamma 2S)
      GABAA receptor subunit mRNAs in the fronto-parietal motor (FrPaM) cortex and the
      hippocampus. Rats receiving the long-term treatment with diazepam developed a
      tolerance to the amnesic effect of this drug and showed a decrease (30-50%) in
      the expression of mRNAs encoding for alpha 1 gamma 2L, gamma 2S GABAA receptor
      subunits, an increase, by approximately 30%, of the expression of mRNA of the
      alpha 5 subunit in the FrPaM cortex and a decrease, by approximately 25%, in the
      expression of mRNA, of the alpha 1 subunit in the hippocampus. These changes of
      subunit mRNA expression and the tolerance to the amnesic effect of diazepam
      returned to control values 72 hr after termination of the long-term treatment
      with diazepam. No tolerance to the amnesic effect of diazepam and no changes in
      GABAA receptor subunit mRNA expression were found in rats undergoing long-term
      treatment with imidazenil.

PMID- 9014163
TI  - Chronic administration of antipanic drugs alters rat brainstem GABAA receptor
      subunit mRNA levels.
AB  - Mental illness, such as panic disorder and depression, display comorbidity as
      well as common therapeutic treatments. These features point toward a common
      etiology and/or therapeutic pathway. There is evidence to suggest that some
      antipanic agents may mediate their effects by altering gamma-aminobutyric acid
      (GABA) levels or by modulating the activity of the GABAA receptor. Chronic
      stimulation of GABAA receptors by agonists or modulators results in changes in
      the pharmacological properties of the receptor concomitant with alterations in
      the expression of specific GABAA receptor subunits. Therefore, we investigated
      the hypothesis that long-term exposure to three antidepressant/antipanic drugs
      (imipramine, phenelzine and alprazolam) would produce changes in the steady-state
      levels of those subunit mRNAs that are believed to encode the major GABAA
      receptor subtype. Further, these changes in gene expression would be different to
      those produced by the non-antipanic anxiolytic (buspirone). We report here that,
      following a 21 day treatment, imipramine, phenelzine, alprazolam and buspirone
      differentially altered rat brainstem levels of GABAA receptor alpha 1-, beta 2-
      and gamma 2-subunit RNAs. These results demonstrate novel actions of
      antidepressant/antipanic drugs on GABAergic neurotransmission.

PMID- 9014164
TI  - Benzodiazepine site pharmacokinetic/pharmacodynamic quantification in man: direct
      measurement of drug occupancy and effects on the human brain in vivo.
AB  - To date, the study of the relationship between drug occupancy and action in the
      brain has had to rely on the use of either animal models or of indirect kinetic
      measures in man, e.g. serum concentrations of unbound drug (as a measure of
      "free" drug in brain). We describe the first set of experiments which directly
      measure agonist-induced changes in both pharmacodynamic effects and
      pharmacokinetic parameters simultaneously and which demonstrate the feasibility
      of these studies in man. Five healthy volunteers each had two PET scans using
      [11C]flumazenil (a radiolabelled benzodiazepine site antagonist) as part of a
      study investigating kinetic models and the relationship between occupancy and
      effect of benzodiazepine site ligands. In both studies the [11C]flumazenil was
      displaced from the brain by infusion of midazolam administered i.v. 30 min into
      the scan. In one study a higher dose of midazolam was administered than in the
      other (range 12.5-50 micrograms/kg). Time-activity curves of the concentration of
      radioligand were derived in 17 different brain regions using a stereotactic
      automatic method of region selection. We demonstrated that there are significant
      differences in an index of occupancy, induced by the two different doses of
      midazolam, both across brain regions and within subjects. There was a significant
      correlation between measured occupancy index change and pharmacodynamic effects
      as measured by the peak change in beta 1 spectral power on EEG. There was no
      significant correlation between dose administered and EEG changes; plasma
      concentrations of midazolam were correlated with the occupancy index and with the
      EEG measures. In addition, we have demonstrated that a non-regional total index
      of brain occupancy can be obtained by analysing the non-tomographic data obtained
      with the PET scanner (total radioactivity counts head curve) and that this index
      shows significant correlations both with the dose administered and with the
      pharmacodynamic measure. This last finding validates the use of other non
      tomographic counting techniques (Malizia et al., 1995a) where an index of
      displacement can be obtained after the administration of less than 1% of the dose
      of radiation needed for a PET study. These studies are likely to be useful in
      human psychopharmacology, in particular in the assessment of tolerance and of
      putative changes in benzodiazepine sensitivity in anxiety disorders. The same
      principles can be applied to other ligand studies and will be useful to validate
      current PK/PD models.

PMID- 9014165
TI  - Blunted furosemide action on cerebellar GABAA receptors in ANT rats selectively
      bred for high alcohol sensitivity.
AB  - Furosemide specifically reverses the inhibition by gamma-aminobutyric acid (GABA)
      of t-[35S]-butylbicyclophosphorothionate ([35S]TBPS) binding and increases the
      basal [35S]TBPS binding to the cerebellar granule cell layer GABAA receptors. For
      the selectivity of furosemide, an interplay between GABAA receptor alpha 6 and
      beta 2 or beta 3 subunits is needed. We have now investigated the furosemide
      sensitivity of cerebellar [35S]TBPS binding in the alcohol-sensitive (ANT) rat
      line that harbors a pharmacologically critical point mutation in the alpha 6
      subunit [alpha 6 (Q1000)], increasing benzodiazepine affinity of the normally
      insensitive alpha 6-containing receptors. ANT receptors were less efficiently
      affected by furosemide, while a normal GABAA receptor antagonism was observed
      with a specific GABAA receptor antagonist SR 95531. Reduced [3H]muscimol binding
      in ANT samples and small alterations in situ hybridization signals for alpha 1,
      alpha 6, beta 2, beta 3, gamma 2 and delta subunit mRNAs failed to correlate with
      impaired cerebellar furosemide efficacy in individual animals. The alpha 6 (q100)
      ANT mutation was not responsible for the reduced efficacy of furosemide in the
      ANT rat line, as judged from the potent furosemide antagonism in recombinant ANT
      type alpha 6 (Q100)beta 3 gamma 2 receptors. This data suggest that presence of a
      novel abnormality in the structure and/or expression of alpha 6 subunit
      containing GABAA receptors in the ANT rat line.

PMID- 9014166
TI  - The functional basis of ocular dominance: functional MRI (fMRI) findings.
AB  - Changes in cortical metabolism and cerebral perfusion may be recorded non
      invasively with functional magnetic resonance imaging (fMRI). In pilot
      experiments, using fMRI with photic stimulation, we found differences between
      activated areas when the left or the right eye was stimulated separately. In this
      study we investigated whether this could be explained by ocular dominance. We
      studied 26 healthy volunteers (mean age 23.3 +/- 3.5 years). Ocular dominance was
      determined by means of the near-far alignment test. fMRI-measurements consisted
      of a double-slice gradient echo sequence. Slices were acquired placed parallel on
      either side of the calcarine fissure. Visual stimulation was done with goggles
      with two LED matrices (red light, 8 Hz); each in front of one eye. In each
      subject, the left and right eye were stimulated separately and together, in a
      randomly alternating order. Twenty-two subjects showed activation, of whom eight
      subjects had a dominant left eye and 14 a dominant right eye. In general the size
      of the activated area was bigger upon stimulation of the dominant eye. The
      difference with the area upon stimulation of the non-dominant eye was
      statistically significant in the right eye dominant group. These results indicate
      that the dominant eye actually activates a larger area of the primary visual
      cortex than the non-dominant eye. This provides for the first time a functional
      basis for the concept of ocular dominance.

PMID- 9014167
TI  - Early effects of basic fibroblast growth factor on foetal rat mesencephalic cell
      suspensions.
AB  - Mesencephalic cell suspensions are used, experimentally but also clinically, to
      compensate for neurological deficiencies, by implantation into the striatum.
      Here, we have studied the metabolism of mesencephalic cell suspensions obtained
      from rat embryos by measuring heat dissipation, oxygen consumption, ATP and
      lactate production. The effect of basic fibroblast growth factor (bFGF) at a 50
      ng/ml concentration on these parameters was studied in order to assess the effect
      of in vitro exposure of cell suspensions to this trophic factor. Heat production
      and oxygen consumption were low, as could be expected from an immature nervous
      tissue, and they further decreased after addition of bFGF. This trophic factor
      decreased the total ATP concentration and increased the lactate production. The
      viability of the cell suspensions was reduced by nearly a half, 2 h after the
      addition of bFGF, and numerous fragmented nuclei were observed. It seems that, in
      contrast to the neuroprotective effect of bFGF on mesencephalic cultures and
      nigrostriatal neurons, this factor could have an initial sorting effect in the
      development of mesencephalic structures.

PMID- 9014168
TI  - Tetrodotoxin-resistant Na+ spikes of C fibers have at least two subtypes in the
      isolated bullfrog sciatic nerve.
AB  - The C fiber compound action potentials (C-CAPs) were studied for their properties
      with the vaseline gap method from the isolated bullfrog sciatic nerve. Two
      components (the fast and the slow C-CAPs) were found to be Na+ dependent and
      tetrodotoxin-resistant. The conduction velocities of the fast and the slow C-CAPs
      were 0.61 +/- 0.06 m/s (n = 13) and 0.42 +/- 0.05 m/s (n = 8), respectively;
      their time constants were 11.4 +/- 1.7 m/s and 16.3 +/- 1/7 ms, respectively,
      with both parameters being significantly different at P < 0.01. The slow C-CAP
      had about 1.3 times higher threshold than that of the fast C-CAP, with a
      significant difference (P < 0.01). They showed differential sensitivity to
      lidocaine and Cd2+. Capsaicin reduced the amplitudes of both fast and slow C
      CAPs, but not abolished. These findings indicate that C fibers have at least two
      subtypes with different properties.

PMID- 9014169
TI  - Protective effect of carbidopa on hydroxyl radical generation in the rat striatum
      by dopamine.
AB  - The effect of L-3,4-dihydroxyphenylalanine (L-DOPA) on the generation of hydroxyl
      free radicals (.OH) was investigated using striatal microdialysis technique.
      Salicylic acid in Ringer's solution (0.5 nmol.microliters-1.min-1) was infused
      directly through a microdialysis probe to detect the generation of .OH as
      reflected by the formation of dihydroxybenzoic acids (DHBA) in the striatum. When
      L-DOPA (0.1 mM; 1 microliter.min-1) was infused in the rat brain, the level of
      3,4-dihydroxyphenylacetic acid (DOPAC) gradually increased in a time-dependent
      manner. In addition, a marked elevation of DHBA was observed. However, in the
      presence of carbidopa, a decarboxylase inhibitor, the elevation in DHBA formation
      was not observed. These results suggest that carbidopa may suppress the .OH
      generation by dopamine (DA).

PMID- 9014170
TI  - Immunohistochemical study of advanced glycation end products in aging and
      Alzheimer's disease brain.
AB  - Advanced glycation end products (AGEs) in the brain were immunohistochemically
      examined in Alzheimer's disease (AD) and aging using anti-AGE antibody
      recognizing mainly carboxymethyllysine. AGE positive staining diffusely located
      in the neuronal perikarya of hippocampus and parahippocampus in AD and aged
      brains without dementia, but not in young brains less than 17 years of age. Extra
      neuroperikaryal AGE deposits were also detected in the neuropil of AD and aged
      brains. The extra-neuroperikaryal AGE deposits markedly increased in AD brains as
      compared to aged brains. These AGE-positive deposits in the neuropil were not
      related to the senile plaque identified by anti-beta amyloid protein antibody.
      These findings suggest a potential link of AGE accumulation in the central
      nervous system to the aging process of neurons and the degenerating process of AD
      neurons.

PMID- 9014171
TI  - Central and peripheral myelin in the rat cochlear and vestibular nerves.
AB  - In the bipolar neurons of vertebrate cochlear and vestibular nerves, the myelin
      envelopes without interruption the axon, the perikaryon and the dendrite. The
      perikaryal myelin is thin and partially loose, whereas axon and dendrite are
      enveloped by compacted myelin. The expression of protein 0 and myelin basic
      protein, constituents of peripheral and central myelin respectively, has been
      investigated in the rat by immunohistochemical study at the light microscopic
      level. Our data indicate that both in the cochlear and vestibular nerves the
      myelin of the perikaryon and dendrite is composed by specific peripheral myelin
      proteins. The axon segment between the perikaryon and the transitional zone
      expresses peripheral myelin proteins in the cochlear nerve, while both types of
      myelin proteins are present in the vestibular nerve. Between the transitional
      zone and the brainstem the myelin of the axon is exclusively of the central type.
      The peripheral-central myelin transitional zone is in close proximity to the
      axonal pole in the vestibular ganglion cells, while in the cochlear nerve it is
      near the spiral foramina, at variable distance from the axonal pole of ganglion
      cells.

PMID- 9014172
TI  - Loss of basic fibroblast growth factor in the subcommissural organ of old
      spontaneously hypertensive rats.
AB  - The immunocytochemical localization of basic fibroblast growth factor (bFGF) was
      studied in subcommissural organ (SCO) of aged-matched normotensive Wistar-Kyoto
      (WKY) and spontaneously hypertensive (SH) rats at 10, 14 and 18 months of age
      using a polyclonal antibody against bFGF. The bFGF-like immunoreactivity (bFGF
      ir) was observed in SCO ependymal cells of young and old normotensive rats.
      However, a progressive loss of bFGF-immunopositive ependymal SCO cells was
      observed with age in SH rats (27.24, 57.5 and 96.9% in 10, 14 and 18 months old
      respectively) compared with aged-matched WKY normotensive rats. Considering the
      potential role of the SCO in sleep regulation and sodium homeostasis, which are
      altered in essential hypertension, these data show a new neuroendocrine anomaly
      to be added to the many others previously observed in this rat strain, when they
      develop hypertension as they get old.

PMID- 9014173
TI  - Parameters influencing ectopic gene expression in Aplysia neurons.
AB  - DNA microinjection for expressing exogenous genes in Aplysia neurons has been
      very useful for analyzing not only functions of encoded proteins, but also
      regulations of gene expression in the nervous system. Some of the factors that
      affect expression of foreign genes microinjected into Aplysia neurons are
      described. The effect of the DNA form (supercoiled or linear) and promoter
      modification in the expression vectors are analyzed as well as buffer composition
      and DNA concentration in the microinjection solution. The time course of reporter
      gene expression was also monitored. Reporter gene expression was first detected
      as early as 1 h and maintained at a high level even until 7 days after
      microinjection. The presence of AP-1 enhancer in the promoter region of the
      expression vectors was essential in driving a high-level constitutive expression
      of reporter genes. Particularly, a pNEX derivative containing eight copies of AP
      1 enhancer drove constitutive overexpression more effectively than ones harboring
      either four or 12 copies of AP-1 enhancer. We also found that a prokaryotic
      promoter/operator from E. coli lacZ gene placed upstream from an eukaryotic
      enhancer/promoter repressed the expression of the downstream reporter gene in
      Aplysia neurons.

PMID- 9014174
TI  - Improved neurochemical recovery of 6-hydroxydopamine-lesioned postganglionic
      sympathetic neurons by nerve growth factor in the adult rat.
AB  - Intraplantar injections of nerve growth factor (NGF; five injections of 4
      micrograms each in 30 h intervals) were able to locally improve the recovery of
      the noradrenaline content in 6-hydroxydopamine (6-OHDA)-lesioned sympathetic
      nerves in adult rats. Whereas 8 days after the 6-OHDA treatment the noradrenaline
      content in the paw skin was still less than 10% of control, it reached up to 40%
      of control levels in NGF injected paws. Intraplantar NGF also significantly
      improved the recovery of the noradrenaline content in the innervating sciatic
      nerve, but not in distant tissues. The NGF-induced recovery of noradrenergic
      nerves was independent of the presence of sensory peptidergic afferents and it
      could not be mimicked by a local inflammatory response known to raise endogenous
      NGF production. These results show that rather low doses of exogenous NGF were
      able to locally restore peripheral noradrenergic nerves after an acute neurotoxin
      lesion.

PMID- 9014175
TI  - Differential downregulation of protein kinase C isoforms in spreading depression.
AB  - Spreading depression (SD) is a propagating depolarization of populations of
      neurons induced by intense electrical, chemical, or mechanical stimulation, which
      has been proposed to be an important mechanism in the aura of migraine. SD is
      characterized by a transient loss of synaptic transmission and thus may involve
      signal transduction mechanisms known to modulate synaptic strength. To examine
      the underlying pathophysiological molecular mechanisms of SD, we analyzed the
      regulation of eight protein kinase C (PKC) isoforms by immunoblot during SD
      induced by a high-intensity stimulus of synaptic afferents in the CA1 region of
      hippocampal slices. We observed a downregulation of the conventional (alpha, beta
      I, beta II, gamma) and the novel (delta, epsilon, eta) PKC isoforms in SD, but no
      change in the atypical isozyme (zeta). The coordinate downregulation of multiple
      PKC isoforms may be important in the functional depression of neuronal activity
      in SD. In contrast, the atypical zeta, and its constitutively active fragment PKM
      zeta, is a specific PKC isozyme that has been implicated in the maintenance of
      long-term potentiation (LTP) and long-term depression (LTD), widely studied
      models for the mechanism of memory. The stability of PKC zeta and PKM zeta in SD
      indicates that a molecular mechanism for the maintenance of LTP/ LTD is
      relatively resistant to alterations that occur during pathophysiologically large
      ionic fluxes. This result could help to explain the retention of information
      stored in the cortex despite the massive release of excitatory neurotransmitter
      and neuronal depolarization that may occur during the migrainous aura.

PMID- 9014176
TI  - CGRP-immunoreactive nerve fibers projecting to lumbar facet joints through the
      paravertebral sympathetic trunk in rats.
AB  - We previously reported that the L5-6 facet joint is innervated from DRGs from L1
      to L5 and the paravertebral sympathetic ganglia from T12 to L6 in rats. In the
      present study, to determine the sensory pathway from L5-6 facet joint, we placed
      the fluorescent carbocyanine dye, DiI, in the L5-6 facet joint, and examined the
      paravertebral sympathetic trunks and ganglia bilaterally. We found some DiI
      labeled nerve fibers exhibiting calcitonin gene-related peptide (CGRP)
      immunoreactivity, and some DiI-labeled neurons surrounded by CGRP-immunoreactive
      varicose fibers in the ganglia. The results suggest that a sensory pathway from
      the L5-6 facet joint to L1 and/or L2 DRGs is present in the paravertebral
      sympathetic trunk, and that sensory nerve fibers may connect with sympathetic
      postganglionic neurons projecting to lumbar facet joints.

PMID- 9014177
TI  - Direct projections form catecholaminergic neurons in the caudal ventrolateral
      medulla to vasopressin-containing neurons in the supraoptic nucleus: a triple
      labeling electron microscope study in the rat.
AB  - Direct projections form the A1 catecholaminergic cell group in the caudal
      ventrolateral medulla (CVLM) to arginine-vasopressin-containing (AVP-containing)
      neurosecretory neurons in the hypothalamic supraoptic nucleus (SON) were examined
      electron microscopically in the rat by a triple-labeling technique in which an
      anterograde tract-tracing method of wheat germ agglutinin-conjugated horseradish
      peroxidase (WGA-HRP) was combined with immunocytochemistry for tyrosine
      hydroxylase (TH) and that for AVP. In the SON, TH-like immunoreactive axon
      terminals which were labeled with WGA-HRP injected in the CVLM were in synaptic
      contact with neuronal profiles with AVP-like immunoreactivity. The results
      indicate that AVP-containing neurons in the SON receive monosynaptic
      catecholaminergic synaptic input from the CVLM.

PMID- 9014179
TI  - Morphine microinjected into the nucleus tractus solitarius and rostral
      ventrolateral medullary nucleus enhances somatosympathetic A- and C- reflexes in
      anesthetized rats.
AB  - The modulatory effects of morphine microinjected into localized areas of the
      brainstem on somatosympathetic A- and C-reflexes were examined in urethane
      anesthetized rats. Somatosympathetic A- and C-reflexes were elicited in a branch
      of the inferior cardiac nerve by electrical stimulation of myelinated (A) and
      unmyelinated (C) afferent fibers in the tibial nerve. Morphine (0.002-0.2
      microgram/50 nl) was microinjected into the rostral, intermediate and caudal
      parts of the nucleus tractus solitarius (NTS), the rostral ventrolateral
      medullary nucleus (RVLM), the caudal ventrolateral medullary nucleus (CVLM), the
      locus coeruleus (LC), the raphe magnus (RM), the periaqueductal gray (PAG), and
      the accumbens nucleus (Acb). Microinjections of morphine (0.2 microgram) into the
      intermediate and caudal NTS produced significant augmentations of the A- and C
      reflexes, C-reflexes being more markedly enhanced than A-reflexes. Microinjection
      of morphine (0.2 microgram) into the RVLM produced a prominent increase in the C
      reflex, the threshold dose for a significant increase being 0.02 microgram
      morphine. Microinjection of morphine up to 0.2 micrograms/50 nl into the other
      areas mentioned above had no significant effect on either reflex component. All
      opiate-induced increases of the reflex discharges could be reversed by
      intravenous application of naloxone (2 mg/ kg). The reflex augmentation induced
      by microinjection of morphine into the NTS may be caused by suppressing
      inhibitory baroreceptor information or by enhancing excitatory chemoreceptor
      information in the NTS. Augmentation of the C-reflex induced by microinjection of
      morphine into the RVLM may be caused by facilitating C-reflex pathways or by
      suppressing inhibitory neural circuits involved in the C-reflex within the RVLM.

PMID- 9014178
TI  - Nitric oxide stimulates both the basal and reflex release of vasopressin in
      anesthetized rats.
AB  - In view of the fact of the high concentration of neuronal nitric oxide synthase
      (NOS) in the supraoptic and paraventricular nuclei as well as the posterior
      pituitary, it has been supposed that nitric oxide (NO) may be involved in the
      regulation of hormone secretion from these sites. In the present study, L
      arginine, the precursor of NO, and N(omega)-nitro-L-arginine methyl ester (L
      NAME), the NOS inhibitor, were intracerebroventricularly (i.c.v.) administered
      into the pentobarbital anesthetized rats. The results showed that plasma arginine
      vasopressin (AVP) concentration increased after the injection of L-arginine (1.0
      mg in microliters, i.c.v.) and decreased after the L-NAME (270 micrograms in 5
      microliters, i.c.v.). The elevated plasma AVP level in response to short-term
      hypotension induced by intravenous infusion of sodium nitroprusside was also
      significantly reduced by i.c.v. administration of L-NAME. The results indicate
      that NO acts as a stimulating factor to both the basal and reflex release of AVP,
      opposing the view that NO plays an inhibitory role in the regulation of AVP
      secretion.

PMID- 9014180
TI  - Mutation of potential N-linked glycosylation sites in the Alzheimer's disease
      amyloid precursor protein (APP).
AB  - In order to study the mechanism of intracellular sorting and processing of the
      Alzheimer's disease amyloid precursor protein (APP), we deleted two potential N
      linked glycosylation sites of APP by site-directed mutagenesis. Substitution of
      alanines for the critical asparagine residues Asn467 and Asn496 was performed.
      Wild-type and mutant APPs were expressed in COS-1 cells by cDNA transfection and
      the expressed of the protein and secretion of N-terminal large fragment was
      observed. The initial secretion of the mutant APP appeared to be slow compared
      with wild-type. In addition, we found that a distinct APP fragment, the cytosolic
      form, is transiently increased in the cytosol fraction of COS-1 cells. These
      results suggest that aberrant processing occurs following the expression of a
      mutant APP with Ala substituted for Asn, and that glycosylation may modulate the
      intracellular sorting of APP.

PMID- 9014181
TI  - Connections of the dorsomedial part of the nucleus intercollicularis in a male
      non-songbird, the Grey partridge: a tract-tracing study.
AB  - Vocal control systems have been poorly investigated in non-songbirds. In this
      study we describe descending neural pathways to the dorsomedial portion of the
      nucleus intercollicularis (ICo) in a galliform (male Grey partridges) by means of
      the DiI in vitro tracing technique. The simple and sex-dimorphic vocalizations of
      partridges, which have a critical role in sexual selection, favour this species
      as a model system for the study of vocal control mechanisms. Our data demonstrate
      that the ICo, an important site mediating the activation of vocal behavior in all
      birds, receives afferents from several important higher centers: the nucleus
      pretectalis, the tuberoinfundibular hypothalamic region, the dorsal thalamus, the
      preoptic region and the paleostriatal region. Efferent connections of the ICo
      were directed mainly to the hypothalamic area. This complex neural pathway is
      consistent with a major role of ICo in male courtship and vocal performance
      control.

PMID- 9014182
TI  - Chronic haloperidol treatment decreases preproenkephalin mRNA in the anterior
      pituitary: a study by solution-hybridization-RNase protection assay.
AB  - By solution-hybridization-RNase protection assay, the preproenkephalin (PPek)
      mRNA in the anterior pituitary (AL) of male rats was found to decrease by 42%
      after 3 weeks haloperidol treatment. It is concluded that dopamine may stimulate
      the AL enkephalinergic system at the level of gene expression.

PMID- 9014183
TI  - Unlike MPP+, apoptosis induced by 6-OHDA in PC12 cells is independent of
      mitochondrial inhibition.
AB  - The mechanisms of 6-hydroxydopamine (6-OHDA) cytotoxicity were studied in vitro
      using the PC12 cell line. Following a 24 h exposure, this neurotoxin induced
      apoptosis and a dose-dependent decrease in cell survival. The presence of
      monoamine oxidase inhibitors, tranylcypromine and clorgyline, together with 6
      OHDA had neither synergistic nor protective effects. Unlike 1-methyl-4
      phenylpyridinium (MPP+), 6-OHDA toxicity to PC12 cells remained unchanged when
      glycolysis was prevented by either depleting glucose from the culture medium or
      growing the cells in low-glucose medium containing 2-deoxy-glucose. These results
      suggest that the inhibition of mitochondrial respiration is not responsible for
      the cell death induced by 6-OHDA.

PMID- 9014184
TI  - [Interpretation of bone and cartilage magnetic resonance images and their future
      prospect].

PMID- 9014185
TI  - [Twenty-eight years' treatments using high tibial osteotomy with development of Y
      blade plate and postoperative repair of degenerated cartilage in the
      osteoarthritic knee].

PMID- 9014186
TI  - [More than 15 years' follow-up results after high tibial osteotomy for
      osteoarthritis of the knee].

PMID- 9014197
TI  - Human phenol sulfotransferase pharmacogenetics: STP1 gene cloning and structural
      characterization.
AB  - Sulfate conjugation catalysed by phenol sulfotransferase (PST) is an important
      pathway in the metabolism of many drugs. Two isoforms of PST have been
      characterized biochemically in human tissues-a thermostable (TS), or phenol
      metabolizing (P) and a thermolabile (TL), or monoamine-metabolizing (M) form.
      Pharmacogenetic studies of TS and TL PST activities in the human blood platelet
      showed that the activities of these two isoforms were regulated by separate
      genetic polymorphisms. Subsequently, a series of TS PST cDNAs were cloned, and,
      based on sequence homology, those cDNAs could be classified as members of two
      separate subgroups, designated here as 'TS PST1' and 'TS PST2'-indicating the
      existence of three rather than two PST isoforms; TS PST1, TS PST2 and TL PST. The
      genes encoding TS PST2, STP2, and TL PST, STM, have been cloned, structurally
      characterized and mapped to chromosome 16-the same chromosome on which the TS
      PST1 gene, STP1, is localized. As a step toward molecular pharmacogenetic studies
      of sulfate conjugation in humans, we set out to clone and structurally
      characterize STP1, the remaining uncharacterized human PST gene. We found that
      STP1 spanned approximately 4.4 kb and contained 9 exons. The first two exons, IA
      and IB, were identified by performing 5'-rapid amplification of cDNA ends (RACE)
      with human liver cDNA as template. Exons IA and IB were noncoding and represented
      two different cDNA 5'-untranslated region sequences. No canonical TATA box
      sequences were present within the 5'-flanking regions of the gene, i.e. regions
      flanking exons IA and IB. Finally, use of the long polymerase chain reaction made
      it possible to determine that STP1 is located approximately 45 kb 5'-upstream
      from STP2 on the short arm of human chromosome 16. Cloning and structural
      characterization of STP1, when combined with knowledge of the structures of STP2
      and STM, will make it possible to study the molecular basis for the genetic
      regulation of PST activity in human tissue.

PMID- 9014198
TI  - Contribution of human cytochrome P450 to benzo[a]pyrene and benzo[a]pyrene-7,8
      dihydrodiol metabolism, as predicted from heterologous expression in yeast.
AB  - The metabolism of benzo[a]pyrene (B[a]P) and its proximate mutagen B[a]P-7,8
      dihydrodiol (7,8-diol) was investigated in the presence of human microsomal
      epoxide hydrolase and P450 1A1, 1A2, 2C8, 2C9, 2C18, 2C19, 2D6 and 3A4 expressed
      in the yeast Saccharomyces cerevisiae. P450 1A1 had the highest turnover numbers
      for the formation of all B[a]P metabolites, including phenols and dihydrodiols.
      P450 1A2, 2C8, 2C9, 2C18, 2C19 and 3A4, which are well represented in the liver,
      gave rise to the formation of appreciable amounts of 3-hydroxy-B[a]P and of some
      dihydrodiols from B[a]P. When 7,8-diol was used as substrate, P450 1A1 also
      exhibited the highest turnover numbers for the formation of tetrols, the
      hydrolysis products of the diolepoxides, whereas P450 1A2, 2C8, 2C19 and 3A4
      showed moderate activities. In order to test the validity of the yeast system,
      the contribution of each P450 isoform to B[a]P and 7,8-diol metabolism was
      evaluated as the product of the turnover numbers of recombinant P450s by specific
      contents of each P450 in human liver microsomes. Calculated formation rates for
      each B[a]P and 7,8-diol metabolite globally matched experimental values. There is
      evidence that P450 3A4 and 2C9 play a major role in the formation of 3-hydroxy
      B[a]P from B[a]P. Accumulation of the proximate mutagen 7,8-diol was predicted to
      be mainly driven by P450 1A2, 2C9 and 2C19, while formation of the genotoxic
      diolepoxides from 7,8-diol appeared to be dependent on P450 1A2 and 3A4 in the
      liver.

PMID- 9014199
TI  - Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6
      rapid metabolizers.
AB  - The arylamine N-acetyltransferase (NAT2) is a polymorphic enzyme which is
      expressed in the liver in a genotype-determined manner. NAT2 is involved in
      activation and inactivation of carcinogens through N-acetylation. We studied the
      role of this polymorphism in the development of hepatocellular carcinoma (HCC).
      One hundred consecutive patients diagnosed for HCC and 258 healthy volunteers
      were studied for NAT2 genotype. The occurrence of seven enzyme-inactivating and
      silent point mutations in the coding region of the NAT2 gene was studied by
      mutation-specific PCR amplification. An excess of subjects homozygous for NAT2
      loss of function alleles was observed among patients with HCC (68% vs 53.9%
      controls). The relationship between the slow acetylator NAT2 genotype and HCC
      risk is more pronounced in patients lacking serum HBV and HCV markers. The
      additional determination of alleles of the cytochrome P450 2D6 (CYP2D6) gene in
      the same subjects confirmed our previous findings that subjects with two active
      CYP2D6 genes are at increased risk of developing HCC. The genetic polymorphism of
      NAT2 is a relevant factor in the risk for developing HCC (inverse odds ratio slow
      vs rapid = 1.8; 95% CI 1.1-3.0). The inverse odds ratio for subjects with two
      risk genotypes (two defect NAT2 genes and two or more active CYP2D6 genes) is 2.6
      (95% CI 1.6-4.4) for all patients with HCC, and 5.6 (95% CI 1.4-33.3) for
      patients without serum viral markers.

PMID- 9014200
TI  - Imipramine metabolism in relation to the sparteine oxidation polymorphism--a
      family study.
AB  - The relationship between genetic polymorphism and imipramine metabolism has never
      been studied in a family study. A sparteine/mephenytoin test was carried out in
      31 parents and 20 siblings of 18 Danish poor metabolizers of sparteine (PMs). One
      week later, each subject took 25 mg imipramine followed by urine collection for
      24 h. The urinary content of imipramine, desipramine, 2-hydroxy-imipramine and 2
      hydroxy-desipramine was assayed by HPLC. There were 10 PMs (20%; 9.8-33%, 95%
      confidence interval) and 41 extensive metabolizers of sparteine (EMs) among
      parents and siblings. In 26 of the 28 PMs among probands and relatives, there
      were concordance between phenotype and genotype: D6-A/D6-D (n = 2), D6-A/D6-B (n
      = 5), D6-B/(n = 15) or D6-B/D6-D (n = 4). Two PMs were apparently heterozygous
      (EMs), D6-wt/D6-B. Accordingly, based on the present sample of 28 PMs the
      specificity of the genotype test was 100% and the sensitivity was 92.9%. Two EMs
      were homozygous dominant D6-wt/and 39 were heterozygous EMs; D6-wt/D6-D (n = 5),
      D6-wt/D6-B (n = 27), D6-wt/D6-A (n = 6), D6-wt/D6-wt* (unknown mutation) (n = 1).
      As previously reported in a population study the hydroxylation ratios (i.e. 2
      hydroxymetabolite over parent compound) of imipramine were much lower in PMs than
      in EMs. This and the pedigrees confirmed the co-segregation of sparteine
      oxidation, imipramine 2-hydroxylation and the CYP2D6 genotype. None of the
      hydroxylation ratios could separate EMs and PMs completely, mainly because the 2
      hydroxylation of imipramine also depends on P450s other than CYP2D6.

PMID- 9014201
TI  - S-mephenytoin hydroxylation phenotype and CYP2C19 genotype among Ethiopians.
AB  - The polymorphic metabolism of S-mephenytoin and the distribution of two known
      deleterious mutant CYP2C19 alleles was determined among 114 healthy unrelated
      black Ethiopians. Six subjects (5.2%) were poor metabolizers (PMs) of S
      mephenytoin. The frequencies of the defective CYP2C19*2 (CYP2C19m1) and CYP2C19*3
      (CYP2C19m2) alleles were 0.14 and 0.02, respectively. Three of the PMs were
      homozygous for the CYP2C19*2 allele and the remaining three PMs were heterozygous
      for both the CYP2C19*2 and CYP2C19*3 mutant alleles. It is concluded that the
      frequency of PMs for S-mephenytoin is similar in Ethiopians, Zimbabweans and
      Caucasians and that the CYP2C19*3 allele, for the first time identified in a
      black population, together with the CYP2C19*2 allele account for all of the
      defective CYP2C19 alleles among the Ethiopian PMs.

PMID- 9014202
TI  - Lung cancer risk in relation to the CYP2C9*1/CYP2C9*2 genetic polymorphism among
      African-Americans and Caucasians in Los Angeles County, California.
AB  - CYP2C9 is involved in the metabolism of warfarin and a wide array of other
      therapeutic agents. It also appears to play a role, along with other cytochrome
      P450 enzymes, in the metabolism of benzo[a]pyrene, a carcinogen in tobacco smoke.
      A relatively common allelic variant (termed R144C, Cys144 or more recently
      CYP2C9*2) has been described that results in the substitution of cysteine for
      arginine at residue 144 and appears to reduce enzyme activity. We therefore
      examined the possible association between the presence of the CYP2C9*2 variant
      allele and risk of lung cancer using peripheral blood DNA from 329 incident cases
      of lung cancer (152 African-American and 177 Caucasian) and 700 (239 African
      American and 461 Caucasian) population controls in Los Angeles County,
      California. Among the population controls the frequency of the CYP2C9*2 variant
      allele was lower (p = 0.00002) among African-Americans (0.036) than among
      Caucasians (0.100). The presence of the CYP2C9*2 variant allele was not
      associated with a decreased risk of lung cancer; slight but nonstatistically
      significant elevations in risk were observed for both African-Americans [odds
      ratio (OR) 1.22, 95% confidence interval (CI) 0.48-3.11] and Caucasians (OR =
      1.55, 95% CI 0.96-2.48). The ORs were slightly and nonsignificantly elevated for
      all histologic types without substantive variation. The association also did not
      vary materially according to smoking history or whether subjects had the
      homozygous deletion of the GSTM1 gene. We found no support for the hypothesis
      that the CYP2C9*2 variant allele decreases the risk of lung cancer. The role of
      P450s, including CYP2C9, in benzo[a]pyrene metabolism is not fully defined, and
      CYP2C9 catalyses detoxication as well as activation steps. Thus it is not
      inconceivable that diminished CYP2C9 activity could increase metabolic activation
      of benzo[a]pyrene to carcinogenic intermediates. Nonetheless, the small increased
      risk associated the CYP2C9*2 variant allele in our data is consistent with chance
      and should not be overinterpreted.

PMID- 9014203
TI  - Polymorphic enzymes of xenobiotic metabolism as modulators of acquired P53
      mutations in bladder cancer.
AB  - Occurrence or specific types of mutations found in oncogenes or tumor suppressor
      genes may partially be determined by activities of toxifying or detoxifying
      enzymes, such as glutathione S-transferases (GST) M1 and T1, arylamine N
      acetyltransferase (NAT2), microsomal epoxide hydrolase, and the cytochrome P-450
      enzymes 2D6, 1A1, 2A6, and 2E1. In an explorative observational study, 69 bladder
      cancer patients were analysed for acquired mutations in the p53 tumor suppressor
      gene. The same patients were studied for the polymorphic traits of xenobiotic
      metabolism given above which were characterized from blood cell DNA by molecular
      methods. In 20 patients, single point mutations in p53 were detected whereas five
      patients carried two mutations; thus in total 25 mutations were detected. Twelve
      of these were G:C-->A:T transitions, six were A:T-->G:C transitions and seven
      were transversions (three G:C-->T:A, two A:T-->T:A, one G:C-->C:G, and one A:T-
      >C:G). There was no correlation between the types of p53 mutations and lifetime
      smoking or occupational history. In correlation with xenobiotic metabolism, 86%
      of the seven transversion mutations were found in homozygously deficient
      individuals for GSTM1 compared to only 44% of GSTM1 deficiency in the carriers of
      the 18 transition mutations of p53 (p = 0.06). A similar trend was seen for NAT2:
      six of the seven carriers of transversion mutations had two slow NAT2 alleles. No
      apparent associations were seen for the other polymorphic traits which were
      studied. In conclusion, low or deficient activities of two conjugating enzymes of
      foreign compound metabolism, GSTM1 and NAT2, may influence types of acquired
      mutations in p53 in bladder cancer.

PMID- 9014204
TI  - CYP2C19 genotype and phenotype determined by omeprazole in a Korean population.
AB  - Omeprazole (20 mg orally) was given to 103 healthy Korean subjects and blood was
      taken 3 h after administration. The plasma concentration ratio of omeprazole and
      hydroxyomeprazole, used as an index of CYP2C19 activity, was bimodally
      distributed. Thirteen subjects (12.6%) were identified as poor metabolizers (PMs)
      with an omeprazole hydroxylation ratio of 6.95 or higher. Among the 206 CYP2C19
      alleles, CYP2C19*2 and CYP2C19*3 were found in 43 alleles (21%) and 24 alleles
      (12%), respectively. Twelve subjects (12%) carried two defect alleles (*2/*2,
      *2/*3 or *3/*3), 43 subjects (42%) were heterozygous for a mutated (*2 or *3) and
      a wild type (*1) allele, and the remaining 48 subjects (47%) were homozygous for
      the wild type allele. The distributions of the metabolic ratio between these
      three genotype groups were significantly different (Kruskal-Wallis test: p <
      0.0001). The genotypes of 19 additional Korean PMs has been identified in a
      previous mephenytoin study. From a total of 32 PMs, 31 were genotypically PMs by
      analysis of the CYP2C19*2 and *3 alleles and only one PM subject was found to be
      heterozygous for the *1 and *2 alleles. At present it cannot be judged whether
      this subject has a defective allele with a so-far unidentified mutation or a true
      wild type allele. We thus confirm a high incidence (12.6%) of PMs of omeprazole
      in Koreans and of the 32 Korean PMs 97% could be identified by the genotype
      analysis.

PMID- 9014205
TI  - Tuberculosis in Africa: clinical presentation and management.
AB  - In the last decade, sub-Saharan Africa has experienced an explosive increase in
      tuberculosis (TB) cases, largely as a result of the co-epidemic of human
      immunodeficiency virus (HIV) infection. This article reviews the essential
      background epidemiology of TB in sub-Saharan Africa. The clinical features and
      diagnostic problems of pulmonary/extrapulmonary TB in adults and children are
      discussed, particularly in relation to HIV infection. Different treatment
      regimens, their cost, adverse reactions, the ways in which HIV infection
      influences treatment response and the extent of drug resistance are reviewed. The
      recommended approaches to TB control in Africa, including methods used to prevent
      TB through Bacillus Calmette-Guerin and chemoprophylaxis are examined. The
      success achieved by good National TB Control Programmes in some African countries
      allows cautious optimism that this epidemic can be controlled.

PMID- 9014206
TI  - Differentiation, differentiation/gene therapy and cancer.
AB  - "Differentiation, Differentiation/Gene Therapy and Cancer" is intended to suggest
      that an understanding of the cell and molecular biology of cell differentiation
      should advance the development of new cancer therapies. This article, therefore,
      reviews four general topics and their relationship to each other: (1) the
      multistep process of cell differentiation in nontransformed and transformed
      cells, (2) the use of drugs that induce differentiation in vitro as potential
      clinical differentiation therapy agents for cancer, (3) the evolving emphasis on
      gene therapy as a new cancer therapy modality, and (4) the concept of
      differentiation/gene therapy.

PMID- 9014207
TI  - Human P450 metabolism of warfarin.
AB  - The anticoagulant drug warfarin occurs as a pair of enantiomers that are
      differentially metabolized by human cytochromes P450 (CYP). R-warfarin is
      metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10
      hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols. S
      warfarin is metabolized primarily by CYP2C9 to 7-hydroxywarfarin. Potential
      warfarin-drug interactions could occur with any of a very wide range of drugs
      that are metabolized by these P450s, and a number of such interactions have been
      reported. The efficacy of warfarin is affected primarily when metabolism of S
      warfarin is altered.

PMID- 9014209
TI  - Kappa-casein suppresses melanogenesis in cultured pigment cells.
AB  - The effects of bovine milk proteins on melanogenesis in B16 cells were examined.
      Both whey protein isolate and casein exhibited depigmenting properties. Among the
      major protein components of milk--including beta-lactoglobulin, alpha
      lactalbumin, alpha-, beta-, and kappa-casein--only kappa-casein exhibited the
      depigmenting effect. However, the carboxyl terminal peptide of kappa-casein,
      glycomacropeptide, did not show this activity. Also, kappa-casein promoted the
      proliferation of the cells and inhibited the activity of tyrosinase in the cells.
      These results indicate that kappa-casein acts as a melanogenesis-suppressing
      modulator.

PMID- 9014208
TI  - Melanocortin receptors: identification and characterization by melanotropic
      peptide agonists and antagonists.
AB  - Hormones are chemical messengers released from cells to act on and control the
      activity of other cells. Hormonal ligands initiate their actions by interacting
      with receptive substances (Langley, 1906) of the target cells. These receptors
      are proteins that are either integral components of the cell membrane or are
      localized cytoplasmically within cells. Ligand-receptor interaction results in
      either the stimulation or inhibition of cellular activity. Since most hormones
      bind rather specifically to receptors possessed by their target cells, labeling
      of hormonal ligands can be utilized to identify and localize cells within an
      animal. In this report we discuss what is presently known about melanocortin
      receptors (MCRs) as studied by the use of labeled melanotropic peptide ligands.

PMID- 9014210
TI  - Human epidermal melanocyte and keratinocyte melanocortin receptors: visualization
      by melanotropic peptide conjugated microspheres (latex beads).
AB  - The objectives of this research were to determine whether melanocortin receptors
      are characteristic (constant) membrane markers of human epidermal melanocytes.
      Methodologies were developed to visualize melanotropin receptors by scanning
      electron microscopy (SEM). Multiple copies (up to a hundred) of [Nle4,D
      Phe7]alpha-MSH, a superpotent analog of alpha-melanocyte stimulating hormone
      (alpha-MSH), were conjugated to a macromolecular carrier (latex beads:
      microspheres). Incubation in the presence of the melanotropin-conjugated
      microspheres resulted in binding of human normal epidermal melanocytes to the
      beads. Almost every (possibly all) melanocyte possesses melanocortin receptors as
      visualized by SEM. Specificity of binding of the macromolecular conjugate was
      demonstrated by several studies: 1) Binding of melanocytes to the microspheres
      was specific since it could be blocked by prior incubation of the cells in the
      presence of the unconjugated hormone analog; 2) microspheres lacking bound ligand
      did not bind to the melanocytes; 3) microspheres that were first treated with
      reducing agents (e.g., dithiothreitol) did not subsequently bind to melanocytes;
      4) another peptide hormone ligand (e.g., a substance-P analog) attached to the
      latex beads failed to bind to the cells; 5) B16/F10 mouse melanoma cells known to
      express melanocortin receptors bound to the microspheres; and 6) cells of
      nonmelanocyte origin (e.g., mammary cancer cells, small-cell lung cancer cells,
      fibroblasts) did not bind to the macromolecular conjugate. One exception was that
      human epidermal keratinocytes also expressed melanocortin receptors as determined
      by all the criteria established above for epidermal melanocytes. Thus, cell
      specific melanocortin receptors appear to be characteristic cell surface markers
      of epidermal melanocytes and keratinocytes.

PMID- 9014211
TI  - Detection of a fine lamellar gridwork after degradation of ocular melanin
      granules by cultured peritoneal macrophages.
AB  - In the present study we investigated by electron microscopy whether melanin
      granules derived from choroidal melanocytes and retinal pigment epithelium of
      cattle could be degraded in the phagolysosomes of cultured murine macrophages. It
      was found that degradation of ocular melanin is possible by the lysosomes of
      these macrophages. During degradation of the melanin granules an internal
      gridwork of fine concentric, highly ordered membranes, 3-4 nm thick, became
      visible. These membranes may represent remnants of the melanin polymer in the
      original melanosome or may result from self-assembly of degradation products.
      Early-stage melanosome-like structures also appeared during digestion of these
      melanin granules. Melanin granules that seemed to break down into smaller
      fragments without any visible internal structure were also observed.

PMID- 9014212
TI  - The proteolytic potential of normal human melanocytes: comparison with other skin
      cells and melanoma cell lines.
AB  - To understand the contribution of epidermal melanocytes in the proteolytic
      potential of human skin, we have studied melanocytes grown in a low-serum medium
      deprived of phorbol esters, cholera toxin, and other non-physiological
      supplements. We focused on the plasminogen activation system and certain matrix
      metalloproteinases (gelatinases). Supposing that the proteolytic activity of
      cells can influence binding to collagen matrix and its reorganization, we have
      analyzed these parameters as well. We found that human melanocytes secreted
      tissue-type plasminogen activator and utilised it to generate cell-bound plasmin.
      No urokinase-type plasminogen activator was detected in the cultures but its
      receptor was found in cell extracts. Both the 72 kDa and 92 kDa gelatinases were
      secreted by the cells and in equal amounts. In addition, melanocytes secreted the
      wide-spectrum proteinase inhibitor alpha-2-macroglobulin. Melanocytes cast into
      collagen matrices retained a rounded morphology, did not extend processes, and
      were unable to contract collagen lattices. As a control, these parameters were
      investigated in parallel in cultures of human keratinocytes, dermal fibroblasts,
      and two melanoma cell lines. The obtained characteristics suggest that normal
      human melanocytes are proteolytically active cells. This function may pertain to
      skin physiology and pathophysiology.

PMID- 9014213
TI  - Spectrophotometric characterization of eumelanin and pheomelanin in hair.
AB  - Mammalian melanins exist in two chemically distinct forms: the brown to black
      eumelanins and the yellow to reddish-brown pheomelanins. They can be quantified
      by HPLC analysis of pyrrole-2,3,5-tricarboxylic acid (PTCA) and
      aminohydroxyphenylalanine (AHP). We recently developed a spectrophotometric
      method for assaying the total amount of eu- and pheomelanins by dissolving
      melanins in Soluene-350 plus water. In this study, we examined whether absorbance
      at 500 nm (A500) of the Soluene-350 solution reflects the total amount of
      melanins obtained by the HPLC methods, and whether the ratio of absorbances
      between 650 and 500 nm reflects the eumelanin/total melanin ratio in mouse hair,
      sheep wool, and human hair. Our findings were as follows: (1) Total melanin
      levels calculated from A500 values correlate well with those obtained from PTCA
      and AHP values by multiplying with the following factors: for mice, PTCA x 45 +
      AHP x 2.5; for sheep, PTCA x 40 + AHP x 15; and for humans, PTCA x 160 + AHP x
      10. (2) The A650/ A500 ratios were higher (0.25-0.33) in black to brown hair
      while they were significantly lower (0.10-0.14) in yellow to red hair. These
      results indicate that (1) the A500 value can be used to quantify the total
      combined amount of eu- and pheomelanins, and (2) the A650/A500 ratio can serve as
      a parameter to estimate the eumelanin/total melanin ratio. The present method
      provides a convenient way to qualitatively characterize eu- and pheomelanins in
      melanins produced in follicular melanocytes.

PMID- 9014214
TI  - The effect of eicosanoids on the expression of MHC genes in cultured human colon
      cancer cells and mouse colonocytes in vivo.
AB  - Eicosanoids have been implicated in the pathogenesis of cancer and are known to
      regulate the expression of antigens of the major histocompatibility complex
      (MHC). In human colon cancer, we have recently observed that: (a) the expression
      of MHC class I and II antigens are markedly reduced; and (b) the levels of PGE2,
      but not of PGF2 alpha and LTB4, are elevated compared to histologically normal
      mucosa. Therefore, we investigated the effect of PGE2, PGF2 alpha and LTB4 on the
      regulation of MHC class I antigens in two human colon adenocarcinoma cell lines
      and in a murine model of colon cancer. None of these eicosanoids had any
      significant effect on the expression of MHC class I antigens in the human
      colonocytes or the transcription rate of class I genes, with the exception of
      LTB4 which only modestly suppressed the transcription rate. Similarly, 16, 16
      dimethyl-PGE2 had no effect on the expression of MHC class I genes in the
      colonocytes of BALB/c mice treated with the carcinogen dimethylhydrazine. We
      conclude that PGE2, PGF2 alpha and LTB4 did not affect the expression of MHC
      class I antigens in cultured human colon adenocarcinoma cells, and 16, 16
      dimethyl PGE2 did not affect their expression in mice, even when mice were
      treated with a colon carcinogen. Thus, these eicosanoids are an unlikely
      regulator of the observed underexpression of MHC class I antigens in human colon
      cancer.

PMID- 9014215
TI  - The effects of indomethacin, NDGA, allopurinol and superoxide dismutase on
      prostaglandin E2 and leukotriene C4 levels after mesenteric ischemia-reperfusion
      injury.
AB  - In this study, the changes of arachidonic acid metabolites after an ischemia
      reperfusion (I/R) period are investigated. The cyclooxygenase and lipoxygenase
      metabolites were found to be significantly increased after a 45 min period of
      ischemia followed by 5 min of reperfusion. Prostaglandin E2 (PGE2)- and
      leukotriene C4 (LTC4)-like activities did not change in the ischemic period, but
      they both increased after reperfusion. A cyclooxygenase inhibitor indomethacin
      and lipoxygenase inhibitor nordehydroguaretic acid (NDGA) decreased PGE2- and
      LTC4-like activities, respectively, while allopurinol and superoxide dismutase
      (SOD) decreased both activities. According to our results, it can be assumed that
      free oxygen radicals are responsible for the elevation of PGE2- and LTC4-like
      activities and both of these arachidonic acid metabolites and free oxygen
      radicals are the main necrotizing agents in ischemia-reperfusion induced damage.

PMID- 9014216
TI  - Isolation and purification of anticardiolipin antibody from plasma of a patient
      with antiphospholipid syndrome: induced generation of platelet thromboxane A2
      synthesis.
AB  - Antiphospholipid antibodies, particularly anticardiolipin antibodies (aCL) are
      autoantibodies frequently detected in the serum of patients with systemic lupus
      erythematosus (SLE) and the primary antiphospholipid antibody syndrome (PAPS).
      These patients commonly suffer from thrombosis, recurrent fetal loss and
      thrombocytopenia. Since platelet aggregation is pivotal in the genesis of
      thrombosis, we tested the hypothesis that perturbation of platelet membrane by
      aCL/beta 2-glycoprotein (aCL/beta 2GP) complex could trigger the biosynthesis of
      TXA2, a proaggregatory metabolite of AA. The preincubation of 14C-arachidonic
      acid (14C-AA)-labeled platelet pellets (14C-PP) from normal individuals with aCL
      alone followed by incubation with thrombin, resulted in a moderate increase in
      platelet thromboxane B2 (14C-TXB2) biosynthesis when compared to controls
      (without aCL). Similar incubations with beta 2GP-I alone resulted in negligible
      14C-TXB2 biosynthesis. In contrast, the preincubations of normal 14C-PP with
      aCL/beta 2GP-I complex resulted in marked thrombin-induced TXB2 biosynthesis,
      underscoring the requirement of beta 2GP-I in aCL-induced platelet TXB2
      biosynthesis. Taken together, these results are consistent with the view that
      aCL/beta 2GP-I platelet interactions do play a role, at least in part, in
      platelet hyperactivity and thrombosis in antiphospholipid antibody syndrome.

PMID- 9014217
TI  - Effects of nimesulide, a preferential cyclooxygenase-2 inhibitor, on carrageenan
      induced pleurisy and stress-induced gastric lesions in rats.
AB  - Intrapleural injection of carrageenan in rats increased prostaglandin E2 (PGE2)
      production and induced newly synthesized cyclooxygenase-2 (COX-2) in pleural
      exudate cells without affecting COX-1 levels. Nimesulide, a preferential
      inhibitor of COX-2, reduced pleural PGE2 production and was almost as active as
      indomethacin and 10 times more active than ibuprofen. Only COX-1, and nc COX-2,
      was detected in gastric mucosal cells, and PGE2 concentration of gastric mucosa
      was significantly decreased by indomethacin and ibuprofen. The decrease in
      gastric PGE2 production induced by indomethacin and ibuprofen was enhanced in
      stressed rats, resulting in aggravation of stress-induced gastric lesions at anti
      inflammatory doses. However, nimesulide did not produce stress-induced gastric
      lesions even at 30 times the anti-inflammatory dose. This supports the hypothesis
      that inhibition of COX-1 causes unwanted side effects and inhibition of COX-2
      produces anti-inflammatory effects.

PMID- 9014218
TI  - The induction of apoptosis in human cervical carcinoma (HeLa) cells by gamma
      linolenic acid.
AB  - A high concentration (50 micrograms/ml) of gamma-linolenic acid (GLA) induced
      morphological lesions typical of apoptosis, as well as DNA fragmentation, in HeLa
      cells. A lower concentration of GLA (20 micrograms/ml), caused an increased
      proliferating cell nuclear antigen (PCNA) labelling, with 92.7% cells positive,
      compared to 27.7% at a concentration of 50 micrograms/ml GLA. In correlation with
      these results, the number of cells with degraded DNA below the G0/G1 peak
      increased significantly in the 50 micrograms/ml GLA-treated cells, but increased
      only slightly in cells exposed to the lower level of GLA. The high levels of PCNA
      induced by 20 micrograms/ml GLA, in both G1 and S phases, may indicate a state of
      DNA repair synthesis, whilst at the higher concentration of GLA, most of the
      cells became apoptotic. Since apoptosis is associated with the deregulation of c
      Myc expression, and as the Raf-1-MAP kinase cascade activates the expression of c
      Myc and c-Jun, we investigated the effects of 20 and 50 micrograms/ml GLA on the
      Raf-1, c-Myc and c-Jun levels, and on the activity of MAP kinase. The results
      showed that 50 micrograms/ml GLA lowered the activity of MAP kinase. As expected
      with the decreased MAP kinase activity in the cells exposed to the higher level
      GLA, the c-Jun levels were also lowered. The levels of c-Myc, however, were
      increased. It is therefore possible that the deregulated expression of c-Myc in
      the HeLa cells exposed to the high level of GLA (50 micrograms/ml) may contribute
      to the induction of apoptosis in HeLa cells.

PMID- 9014219
TI  - Role of calcium in endothelin-induced contractions and prostacyclin release.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that induces
      characteristically long-lasting contractions. We used rat aortic rings to
      investigate the role of protein kinase C (PKC) in ET-1-induced contractions and
      prostacyclin (PGI2) release. ET-1 (10(-9) M) produced a gradual and sustained
      contraction in rat aortic rings. Pretreatment of aortic rings with different
      doses (10(-9) M and 10(-6) M) of diltiazem (voltage-sensitive L-type calcium
      channel blocker) produced significant inhibition of ET-1- and PDBu-induced
      contractions and PGI2 release. Inhibition was first noted at 10(-9) M and was
      complete at 10(-6) M. Conversely, pretreatment of aortic rings with different
      doses (10(-9) M and 10(-6) M) of calcium channel blockers (thapsigargin, an
      intracellular calcium channel blocker, or conotoxin, a voltage-sensitive N-type
      calcium channel blocker) produced no changes on ET-1-or PDBu-induced contraction
      or PGI2 release. These results provide further support for the concept that PKC
      mediates ET-induced contractions and PGI2 release in rat aortic rings via an
      increase in intracellular calcium and this increase is due to the influx of
      extracellular calcium and not to the release of calcium from the sarcoplasmic
      reticulum.

PMID- 9014220
TI  - Prostanoid biosynthesis in patients with cystic fibrosis.
AB  - The urinary excretion rate (ng/h/1.73 m2) of prostanoids was determined with a
      capillary gas-liquid chromatographic mass spectrometric method in 19 patients
      with cystic fibrosis (CF) aged 1-29 years. Patients with CF showed an increased
      excretion of prostaglandin E2 metabolites (PGE-M) and thromboxane B2 and its
      metabolites at all ages. An imbalance in the excretion pattern of thromboxane B2
      metabolites also suggested a relative impairment of beta-oxidation. There was no
      increased excretion of dinor-6-keto-PGF1 alpha, indicating normal prostacyclin
      biosynthesis. No correlation was found to genotype, clinical score, lung function
      or bacterial colonization but a significant negative relation was found between
      the main prostanoids in the urine and serum phospholipid levels of essential
      fatty acids. The results show that, contrary to the generally accepted decrease
      of prostanoid excretion in essential fatty acid deficiency, patients with CF
      increase their production parallel to the development of the deficiency. Since
      prostanoid synthesis is rate limited by arachidonic acid release, our data
      support a previously presented hypothesis about a pathological regulation of the
      release of arachidonic acid in CF.

PMID- 9014221
TI  - Development of a radioimmunoassay for latanoprost and its application in a long
      term study in monkeys.
AB  - 13,14-Dihydro-17-phenyl-18,19,20-trinor-PGF2 alpha-isopropyl ester (latanoprost)
      is a new prostaglandin drug developed for the treatment of glaucoma. In clinical
      trials a daily dose of 1.5 micrograms is effective in reducing the intraocular
      pressure. In toxicological studies doses from 2 micrograms/eye to 100
      micrograms/eye have been used in various species. This paper reports the
      development and validation of a radioimmunoassay of latanoprost acid (PhXA85) and
      its application to toxicokinetic studies performed in monkeys. An antiserum was
      raised in rabbits by immunization with PhXA85 coupled to BSA at the carboxylic
      acid by the mixed anhydride method. The antibody titre was found to be about
      1:2000 to 1:3000. The cross-reactivity with 13,14-dihydro-15(R,S)-17-phenyl
      trinor-PGF2 alpha, 13,14-dihydro-15(S)-17-phenyl-trinor-PGF2 alpha, dinor-PhXA85.
      17-phenyl-trinor-PGF2 alpha, latanoprost and PGF2 alpha was 46.4, 4.2, 7.6, 2.2,
      0.1 and 0.039%, respectively. The intra-assay precision was between +/-7.7 and
      11.7% (CV) at the level of 320 pg/ml and +/-8.3 and 9.7% with 1280 pg/ml in
      plasma samples from man, monkey, rat and aqueous humour from human and rabbit.
      Similarly, the intra-assay accuracy varied between 95.9 and 102.5% and 89.0 and
      109.0% for the low and high standards, respectively. The inter-assay precision
      and accuracy were between +/- 6.0 and 13.4% and 91.0 and 92.8% in the monkey
      plasma samples. The limit of detection was 3 pg/tube or 30 pg/ml. In a long-term
      study, the acid of latanoprost was rapidly cleared from plasma in monkeys treated
      with eye drops of latanoprost (2 x 3 micrograms/day) over a period of 1 year.

PMID- 9014222
TI  - Prostacyclin and thromboxane A2 synthesis are increased in acute lower limb
      ischaemia.
AB  - Prostacyclin (PGI2) and thromboxane A2 (TXA2) play an important role in the
      pathophysiology of various cardiovascular diseases. The balance between PGI2 and
      TXA2 regulates the interaction between platelets and the vessel wall in vivo. In
      this study we measured PGI2 and TXA2 synthesis by analysing their urinary index
      metabolites 2,3-dinor-6-keto-PGF1 alpha and 11-dehydro-TXB2, respectively, in
      acute (10 patients) and chronic (10 patients) lower limb ischaemia. Both PGI2 and
      TXA2 synthesis were increased about two-fold in patients with acute lower limb
      ischaemia compared to chronic lower limb ischaemia. However, the PGI2/TXA2 ratio
      was more or less the same in acute and chronic lower limb ischaemia. In patients
      with acute lower limb ischaemia caused by thrombotic occlusion, PGI2 and TXA2
      formation were about two times higher than in patients with acute lower limb
      ischaemia caused by embolic occlusion. Elevation of PGI2 and TXA2 synthesis in
      acute lower limb ischaemia may reflect increased platelet-vascular wall
      interactions without changing the PGI2/TXA2 ratio.

PMID- 9014223
TI  - Thromboxane A2 antagonist inhibits leukotriene D4-induced smooth muscle
      contraction in guinea-pig lung parenchyma, but not in trachea.
AB  - Although the bronchoconstriction induced by leukotriene D4 (LTD4) has been
      reported to be partly mediated by thromboxane A2 (TXA2) in the guinea-pig airway,
      it is not known which part of the airway is susceptible to TXA2. In order to
      determine the role of TXA2 in the central and peripheral airways, we compared the
      effect of a TXA2 antagonist on tracheal strips to its effect on parenchymal
      strips of guinea-pigs. Tracheal and parenchymal strips were mounted in a 3.5 ml
      organ bath filled with Krebs-Henseleit solution aerated with 95% O2, 5% CO2 and
      kept at 37 degrees C. After equilibration for 60 min in Krebs solution, the strip
      was contracted by exposure to 10(-5) M of acetylcholine (ACh). Sixty minutes
      after ACh was eliminated, the concentration-response curve to LTD4 (10(-9) M-10(
      7) M) was obtained, and the LTD4-induced contractions were expressed as the
      percent of the contraction evoked by 10(-5) M of ACh. We measured the contractile
      response to LTD4 in the presence or absence of the TXA2 antagonist, BAY u3405
      (10(-8) M-10(-6) M). In the tracheal strips, BAY u3405 had no effect on the LTD4
      induced contraction. However, in parenchymal strips, BAY u3405 significantly
      suppressed the contractile response to LTD4. These results suggest that in the
      central airway LTD4 contracts smooth muscle directly, but that in the peripheral
      airway LTD4 induces smooth muscle contraction both directly and indirectly, via
      TXA2.

PMID- 9014224
TI  - The effect of propolis and its components on eicosanoid production during the
      inflammatory response.
AB  - To investigate the possible mechanism of the therapeutic action of propolis, we
      studied: (a) the effect of propolis, its components, caffeic acid phenethyl ester
      (CAPE), caffeic acid (CA), quercetin and naringenin, as well as the synthetic
      compounds indomethacin (IM) and nordihydroguaiaretic acid (NDGA), and a novel
      lipoxygenase inhibitor N,N'-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)isourea
      (DCHCU) on eicosanoid production by mouse peritoneal macrophages in vitro; (b)
      the effect of IM, NDGA, CA, CAPE, DCHCU and propolis on eicosanoid production
      during acute inflammation in vivo; and (c) the ex vivo and in vivo effect of
      dietary propolis on arachidonic acid metabolism. The ethanol extract of propolis
      suppressed prostaglandin and leukotriene generation by murine peritoneal
      macrophages in vitro and during zymosan-induced acute peritoneal inflammation in
      vivo. Dietary propolis significantly suppressed the lipoxygenase pathway of
      arachidonic acid metabolism during inflammation in vivo. CAPE was the most potent
      modulator of the arachidonic acid cascade among the propolis components examined.

PMID- 9014225
TI  - Effects of non-steroidal anti-inflammatory drugs on prostaglandin E2 production
      by cyclooxygenase-2 from endogenous and exogenous arachidonic acid in rat
      peritoneal macrophages stimulated with lipopolysaccharide.
AB  - Lipopolysaccharide (LPS) stimulated prostaglandin E2 (PGE2) formation and
      induction of cyclooxygenase-2 (COX-2) expression without changing the levels of
      COX-1 protein in rat peritoneal macrophages. Non-steroidal anti-inflammatory
      drugs (NSAIDs) (nimesulide, indomethacin and ibuprofen) strongly inhibited LPS
      stimulated PGE2 production without any effect on COX-2 protein expression,
      suggesting that NSAIDs are active in inhibiting the ability of COX-2 to convert
      arachidonic acid (AA) endogenously released in response to LPS stimulation.
      Exogenous AA can be converted to PGE2 by both COX isoforms even in LPS-stimulated
      macrophages. NSAIDs inhibited PGE2 production from exogenous AA mediated by both
      COX-1 and COX-2. However, the two isoforms interacted differentially with
      different NSAIDs. Furthermore, NSAIDs were distinctly more active in inhibiting
      PGE2 production from endogenous AA than that from exogenous AA. These data
      suggest that PGE2 production through COX-2 from exogenous AA may not be subject
      to the same regulatory processes as that from endogenous AA and the two metabolic
      processes may be differentially sensitive to different NSAIDs.

PMID- 9014227
TI  - Depression among cancer patients.
AB  - This study was done to investigate the frequency of co-morbidity and to
      demonstrate the best method for assessing depression among cancer patients. The
      subjects were 50 (25 male and 25 female) cancer patients and 50 (25 male and 25
      female) medically ill patients. All subjects were interviewed by psychiatrists
      and were administered psychological tests such as SAS (self-rating anxiety
      scale), SDS (self-rating depression scale), POMS (Profile of Mood States), HADS
      (Hospital Anxiety and Depression Scale) and DRP (Depression-related personality
      traits). The psychiatric interview revealed that 44% of cancer patients and 38%
      of the medical patients had mental disorders according to DSM-IV. The most
      frequently observed disorder was depression, which was seen in 28% of the cancer
      patients and 30% of the medical patients. The cancer patients with depression
      scored significantly higher on the DRP and the Anger mood state of POMS than did
      the medically ill patients with depression. In addition, most psychological tests
      employed had no discrimination between depressed and normal subjects among the
      cancer and the medical patients. However, it was found that the Depression scale
      in HADS (HADS-D) split depressed patients from normal subjects since the HADS-D
      was composed of items that were not concerned with physically ill conditions.

PMID- 9014226
TI  - Evaluation of the first Medical Psychiatry Unit in Japan.
AB  - The first Medical Psychiatry Unit (MPU) in Japan was established in 1990. The
      clinical experience during the first 4 years of this unit is presented, and the
      characteristics of the Unit between its first 2 years and its latter 2 years are
      compared. The number of patients, the average length of stay, the primary
      psychiatric disorders, the combined physical diseases and their outcomes are
      presented. The data suggest that while the experience of the MPU is limited, it
      plays an important role in Japan as (i) an appropriate clinical setting for
      patients with combined medical and psychiatric illness, (ii) a strategic model
      for dealing with psychiatric patients in the general hospital, (iii) an
      educational setting for psychiatric residents to become more familiar with
      medicine and surgery, and (iv) an opportunity for non-psychiatric residents to
      become familiar with psychiatric illnesses and treatments.

PMID- 9014228
TI  - A case of possessive state with onset influenced by 'door-to-door' sales.
AB  - Recently in Japan, 'door-to-door sales' has become of concern because it has
      created numerous legal and social problems. In this paper, a 47 year old
      dissociative trance disorder case who presented with possession by God is
      discussed. Specific types of door-to-door sales is known to use superstition and
      folk beliefs as tools to lure customers. In this particular case, these religious
      factors seemed to have played an important role in the precipitation of the
      disorder and its presentation. In addition, the brain-washing environment
      observed in video lectures used in door-to-door sales seemed to play an important
      role in the development of the possessive state. We also performed social
      psychiatric analysis of the occurrence of the possessive state in a city area,
      which has been considered to develop within traditional culture. Phenomenological
      classification by one of the authors was useful for diagnosing underlying
      disorders in the possessive state.

PMID- 9014229
TI  - Recovery of high speed memory scanning after transient global amnesia: a case
      report.
AB  - We described the case of a 59 year old female with transient global amnesia (TGA)
      who had been examined neuropsychologically using Sternberg's paradigm and a
      random number generation (RNG) task on the following day, 1 week and 4 weeks
      after a TGA episode. The slope value of the linear function, a measure of
      cognitive memory scanning speed, decreased with time and showed a marked decrease
      1 week after TGA, suggesting that the stage of serial and exhaustive scanning
      recovered within 1 week. The zero-intercept value, on the other hand, increased
      during 1 week but decreased 4 weeks later and was not related directly to
      recovery from TGA. The performance in RNG task improved 1 week later, but
      deteriorated 4 weeks after the episode. Such a change in RNG was in accordance
      with that of the zero-intercept value, predicting a relationship. It is concluded
      that the subclinical memory deficit, detected with these tasks, persisted longer
      than clinical recovery from TGA.

PMID- 9014231
TI  - A case of Sheehan's syndrome with delirium.
AB  - A 53 year old woman was brought to a psychiatric clinic because of delirium. Upon
      immediate examination, severe hyponatremia (105 mEq/L) was detected. She was
      suspected of having internal diseases and referred to our university hospital.
      When she reached our hospital she was delirious and showed excitement and
      agitation. Her electroencephalogram showed low voltage theta waves (20 microV) in
      all leads. She was hospitalized and diagnosed with acute tonsillar abscess and
      panhypopituitarism based on various endocrine tests. Her past history suggested
      that Sheehan's syndrome had developed after child-bearing at age 31, resulting in
      panhypopituitarism. After administration of antibiotics, the fever and tonsillar
      abscess gradually recovered, and the correction of electrolytes improved the
      level of consciousness, suggesting that the hyponatremia had been closely related
      to the clouding of consciousness. As the subsequent administration of cortisol
      kept the patient's serum sodium levels within the normal range, a decrease in
      plasma cortisol seemed to be the major cause of the hyponatremia. Psychological
      symptoms of panhypopituitarism often included abulia, apathy and occasionally
      coma. However, it is rare for a patient with panhypopituitarism to be
      misdiagnosed as having a psychiatric disease with delirium. This rare case is
      presented.

PMID- 9014230
TI  - Serum carnitine and disabling fatigue in multiple sclerosis.
AB  - The serum concentrations of total, free and acylcarnitine were compared in 25
      patients with multiple sclerosis (MS) and among age- and sex-matched normal
      controls by the new enzymatic cycling method in order to clarify whether the
      fatigue in MS might be due to possible carnitine-related fatty acid metabolic
      abnormalities in the mitochondria of skeletal muscles. Patients with MS were
      divided into those with and those without excessive fatigue. Levels of total and
      free carnitine were not significantly different between MS patients and normal
      controls. Levels of acylcarnitine, whose decrease in chronic fatigue syndrome has
      been reported, were also similar between MS patients and normal controls. There
      was no difference in these carnitine levels between MS patients with and without
      excessive fatigue. We argue that acylcarnitine deficiency and fatty acid
      metabolic dysfunction in mitochondria are not relevant to the excessive fatigue
      in patients with MS, and further explanatory investigations are to be sought.

PMID- 9014232
TI  - No association between c-fos gene polymorphisms and sporadic Alzheimer's disease.
AB  - Although ApoE epsilon 4 is a major risk factor for sporadic Alzheimer's disease
      (AD), 20-30% of sporadic AD patients do not have this allele. This indicates that
      other risk factors are involved in the pathogenesis of sporadic AD. Studies of
      the genetic association between AD and polymorphisms in the c-fos gene, a
      candidate gene for AD, were conducted. The polymorphisms of DsaI in exon 2 and
      Sau3 AI in intron 2 were examined in 89 patients diagnosed as sporadic cases of
      probable AD clinically and radiologically according to the NINCDS-ADRDA criteria.
      This was also undertaken in 96 controls. There was no significant difference
      between the groups in allele frequencies or genotype counts. Although c-fos gene
      as a locus conferring susceptibility to sporadic AD cannot be ruled out, these
      data could not support the hypothesis that a c-fos allele should be another risk
      factor for sporadic AD.

PMID- 9014233
TI  - Two cases of panic disorder treated with autogenic training and in vivo exposure
      without medication.
AB  - The aim of this study was to use autogenic training in combination with in vivo
      exposure in the behavioral treatment of panic disorder without medication. Two
      cases of panic disorder with agoraphobic avoidance were presented. Case 1 was a
      33 year old married female who exhibited mild panic symptoms, and case 2 was a 23
      year old single male who had severe panic symptoms. Both subjects were
      successfully treated with the combination of these two techniques. Treatment
      effects were maintained for 9 years as a follow up in case 1, and for 4 years in
      case 2.

PMID- 9014234
TI  - Hallucinations after a therapeutic dose of benzodiazepine hypnotics with co
      administration of erythromycin.
AB  - A case of repetitive hallucinations during treatment with a therapeutic dosage of
      triazolam (0.25 mg/day) and nitrazepam (5 mg/day) is presented. The patient
      suffered from acute pneumonia and chronic renal failure. Such non-psychotic
      symptoms as anxiety, tremor and depressed feeling were observed initially.
      However, after co-administration of erythromycin (600 mg/day), visual
      hallucinations and abnormal bodily sensations developed repeatedly after each
      administration of triazolam or nitrazepam. This report suggests that
      benzodiazepine hypnotics even at a therapeutic dosage with co-administration of
      erythromycin causes serious psychotic symptoms in vulnerable patients with
      physical complications.

PMID- 9014235
TI  - Effectiveness of shakuyaku-kanzo-to in neuroleptic-induced hyperprolactinemia: a
      preliminary report.
AB  - We investigated the efficacy of Shakuyaku-kanzo-to (TJ-68) in neuroleptic-induced
      hyperprolactinemia in 11 treated schizophrenic patients. The mean plasma
      prolactin level decreased significantly from 28.9 +/- 14.5 ng/mL at baseline to
      22.0 +/- 15.2 ng/mL at 4 weeks. Potassium levels did not change significantly.
      Neither the exacerbation of psychosis nor other adverse effects occurred.

PMID- 9014236
TI  - An anecdote in the dawn of Japanese psychiatry: the tragedy of Dr. Noboru Ishida.
AB  - This is a historical review of the tragic life of a psychiatrist in the dawn of
      Japanese psychiatry, who was sentenced to life imprisonment for first-degree
      murder by an American court and imprisoned in America. The purpose of this
      article is firstly to clarify the strange circumstances under which he was
      sentenced guilty in spite of his psychosis. In the author's opinion there
      appeared to be an incorrectness and injustice of the judicial decision in the
      American court from consideration to the documents of his trial. Secondly, the
      author would like to acknowledge Dr. Ishida's pioneering contributions of the
      Japanese psychiatry which, because of the circumstances, have been long buried in
      the history of Japanese psychiatry.

PMID- 9014237
TI  - Positive selection moments identify potential functional residues in human
      olfactory receptors.
AB  - Correlated mutation analysis and molecular models of olfactory receptors have
      provided evidence that residues in the transmembrane domains form a binding
      pocket for odor ligands. As an independent test of these results, we have
      calculated positive selection moments for the alpha-helical sixth transmembrane
      domain (TM6) of human olfactory receptors. The moments can be used to identify
      residues that have been preferentially affected by positive selection and are
      thus likely to interact with odor ligands. The results suggest that residue 622,
      which is commonly a serine or threonine, could form critical H-bonds. In some
      receptors a dual-serine subsite, formed by residues 622 and 625, could bind
      hydroxyl determinants on odor ligands. The potential importance of these residues
      is further supported by site-directed mutagenesis in the beta-adrenergic
      receptor. The findings should be of practical value for future physiological
      studies, binding assays, and site-directed mutagenesis.

PMID- 9014238
TI  - RT-PCR analysis of shaker, shab, shaw, and shal gene expression in single neurons
      and glial cells.
AB  - We have developed a reverse transcription-polymerase chain reaction (RT-PCR)
      method to examine single neurons and glial cells in the stomatogastric ganglion
      of the spiny lobster Panulirus interruptus for the expression of four members of
      the Shaker family of potassium channel genes. Using this technique we found that
      shaker, shab, shaw, and shal are expressed in 100%, 78%, 100%, and 94% of
      stomatogastric neurons. Furthermore, neuronal shab, shaw, and shal transcript
      levels vary among cells in a manner which is independent of cell size. We also
      detected Shaker family gene expression in glial cells. Shaker, shaw, and shal are
      detectably expressed in 100%, 63%, and 100% of the glial caps examined,
      respectively, while shab gene expression could not be detected in glial cells.

PMID- 9014239
TI  - Automated modelling of the transmembrane region of G-protein coupled receptor by
      Swiss-model.
AB  - Molecular modelling of the transmembrane helices of G-protein coupled receptors
      is an increasingly used method to identify the possible three-dimensional
      environment of key residues. Thereby site-directed mutagenesis experiments, aimed
      at the understanding of the receptor-ligand interactions, can be designed in a
      rational way. The modelling methods are however not generally available to
      experimentalists, and often require expensive software and hardware. To overcome
      these limitations, we have constructed a World Wide Web server for the automated
      protein modelling of user-defined transmembrane helices. The service is freely
      available at this address: http:/(/)expasy.hcuge.ch/swissmod/SWISS-MODEL.++
      +html.

PMID- 9014240
TI  - Modeling and mutagenesis of the human alpha 1a-adrenoceptor: orientation and
      function of transmembrane helix V sidechains.
AB  - A 3-dimensional model of the seven transmembrane helical segments (TMs) of the
      human alpha 1a-adrenoceptor was initially built by analogy to the known structure
      of bacteriorhodopsin. However, the rotational orientation of TM V about its
      helical axis, and the roles of several TM V residues in ligand binding and
      receptor activation remained in question. Accordingly, we determined the effects
      of six site-specific mutations in TM V on binding affinity and functional potency
      of a structurally diverse series of agonists and antagonists. Mutation of Ser 192
      and Phe 193 disrupted the binding of many of the tested ligands, as measured by
      displacement of [3H]prazosin. In addition, mutation of Ser 188, Ser 192, and Phe
      193 disrupted receptor activation, as measured by [3H]inositol phosphate
      formation. On the basis of these results, a specific rotational orientation of TM
      V is proposed as part of a revised receptor model, which also takes into account
      more recently reported information about the structure of rhodopsin. This revised
      alpha 1a-adrenoceptor model accounts for direct interactions which are proposed
      between Ser 188 and Ser 192 and the meta and para hydroxyl groups of
      norepinephrine, respectively, in the G-protein coupled receptor state.

PMID- 9014242
TI  - Production of adrenergic receptors in yeast.
AB  - Using a recombinant yeast strain expressing human beta 2 adrenergic receptors
      under a galactose-inducible promoter, we established conditions for receptor
      production in 1-15 liter fermenter culture. Crucial factors contributing to
      consistent high-level expression included the use of selective glucose-free
      medium, the maintenance of the pH of the culture at 7.2-7.5 and the presence of
      an antagonist. The expression strategy and production conditions used with the
      beta 2 adrenergic receptor were then employed to express the human alpha 2-C2
      adrenergic receptor in Saccharomyces cerevisiae. Galactose-induced yeast cells
      displayed specific, high-affinity [3H]rauwolscine binding and contained a 50-kDa
      species recognized by an alpha 2-C2 receptor specific antiserum. In fermenter
      culture, up to 10(5) high-affinity [3H]rauwolscine binding sites per cell
      (corresponding to 30-60 pmol/mg of protein) were obtained. The high expression
      level combined with relative ease and low cost of scaling-up make yeast a
      promising alternative to mammalian cells for the production of adrenergic and
      other G-protein-coupled receptors for structural studies.

PMID- 9014241
TI  - Effect of subunit composition on GABAA receptor complex characteristics in a
      baculovirus expression system.
AB  - A baculovirus expression system was used to produce functional human recombinant
      GABAA receptors in Sf-9 insect cells in order to study the biochemistry,
      pharmacology and functional characteristics of this receptor complex. We have
      identified and characterized various factors which influence the level of
      receptor expression in multiple virus infections. We have shown that the level of
      expression of the GABAA receptor complex varies with the levels of expression of
      the individual subunits. We have also shown that the assembly process has a
      defined timecourse, and it is dependent upon the ratio of the number of
      infectious virus particles (MOI ratio) of each subunit in multi-virus infections.
      In multiple infections, the capacity for expression of the infected cell is
      shared proportionally by entering virus particles and, there is a direct
      correlation between the amounts of subunit mRNA and levels of subunit protein
      expression, and the amount of ligand binding to expressed protein. Finally,
      reinfection of previously infected cells does not result in subsequent protein
      expression. Knowledge of these various factors allows us to construct recombinant
      GABAA receptor complexes with reproducibility and flexibility with regard to
      subunit composition. By co-expression of alpha, beta, and gamma subunits, both
      the recognition site for GABA and the allosteric (benzodiazepine) modulatory site
      are formed and appear to reproduce the pharmacology of endogenously expressed
      receptors as measured in mammalian CNS. Only a single receptor is produced
      irrespective of the expression levels of the subunits, showing that GABAA
      receptor assembly is highly regulated.

PMID- 9014262
TI  - Protective factors for suicidal black females.
AB  - The purpose of this study is to evaluate the extent to which a model of social
      support may help explain the low suicide rate of Black females. The data are
      taken from the National Institute of Mental Health's Epidemiological Catchment
      Area Study 1980-1985 (United States). The LISREL model examines the direct and
      indirect effects of the background characteristics on attempted suicide as
      mediated by emotional state. Results indicate evidence that for Black and White
      males and females, finding emotional and psychological support in friends and
      family members helps to safeguard against suicide. The most substantial finding
      is that for all all race/sex categories, seeking support from friendship and
      familial resources is negatively related to attempted suicide, whereas seeking
      support from professional resources is associated with an increase in the
      likelihood of a suicide attempt. This increased likelihood of attempted suicide
      may be reflecting populations members' resistance to seeking professional help
      until their emotional state has severely deteriorated.

PMID- 9014263
TI  - Dyadic death: a typology.
AB  - In dyadic deaths, a second victim acts in consort with, is associated with, or is
      killed by a person who, contemporaneous with the first death, then suicides.
      Dyadic deaths thus include both homicide-suicides and suicide pacts. This paper
      describes, suggests organizing dynamics of, and illustrates distinct types of
      dyadic deaths. The proposed typology varies by levels of dominance, dependence
      enmeshment, and the presence or absence of hostility in and between partners.

PMID- 9014264
TI  - Suicide survivors groups: results of a survey.
AB  - Little is known about the nature of suicide survivors groups. Survey responses by
      149 U.S. and Canadian groups are characterized as follows: (1) they are most
      often sponsored by mental health or social service agencies or have no sponsor;
      (2) groups have operated an average of 8 to 9 years; (3) fewer than 10 people
      typically attend monthly or twice monthly meetings; (4) group experience
      predominantly involves sharing personal experiences; (5) leadership generally
      involves either trained facilitators, mental health professionals, or both; (6)
      most groups are open ended; (7) all social/ethnic, income, and adult age groups
      are served, but few children and teenagers attend; and (8) referrals come
      predominantly by word-of-mouth or medical and religious sources. Further research
      is required regarding survivor group attributes and processes.

PMID- 9014265
TI  - The use of simulations to assess the impact of an adolescent suicide response
      curriculum.
AB  - This study employed simulations of encounters with suicidal peers to assess the
      impact of classroom suicide response lessons. Students were asked to anonymously
      write how they would respond, and how concerned they would be in regard to two
      vignettes of troubled peers. On the posttest, students who had participated in
      the classes provided significantly more "tell an adult" responses than those in
      the control group, whereas no differences existed between the groups on the
      pretest. On both the pretest and posttest, all students expressed greater concern
      on the unambiguous vignette (student said that he has been thinking about killing
      himself) than on the ambiguous vignette (student wrote an essay about final
      decisions); and, overall, females expressed greater concern than males. These
      results provide evidence for the efficacy of the classes and the utility of the
      simulations for assessing their impact.

PMID- 9014266
TI  - Deliberate self-poisoning, unemployment and public health.
AB  - The purpose of the present investigation was to explore further the known
      relationship between deliberate self-poisoning and social deprivation. Each
      individual who attended one of Cork city's three casualty departments following
      an act of deliberate self-poisoning in 1988 was examined. The place of residence
      (ward) of each city resident patient was established. The social status of the
      city's 34 wards was estimated using a number of indices obtained from the 1981
      and 1986 census reports and social service records. A comparison was made between
      the 1988 self-poisoning rate for each ward and the rate found in a 1982 study of
      the city. Correlations between self-poisoning rate and seven social deprivation
      indices were found to be significant. Multiple regression, factor, and partial
      correlation analyses were carried out to examine more closely the
      interrelationships between the social deprivation indices. With respect to
      explaining the variation in the self-poisoning rate, unemployment alone performed
      almost as well as all of the indices together and as well as the factors derived
      using factor analysis. The correlation between unemployment and self-poisoning
      rate remained highly significant when the other related variables were controlled
      for. However, at fixed levels of unemployment, these variables were found to be
      independent of the self-poisoning rate. It is suggested that whereas clinical
      intervention may benefit the individual, deliberate self-poisoning as an issue
      requires a public health approach for its resolution.

PMID- 9014267
TI  - Gender and suicide risk among artists: a multivariate analysis.
AB  - Research on mental disorders among male artists has suggested that artists are at
      risk of suicide. However, given that men are higher in suicide risk than women,
      the presumed suicide risk of artists may be an artifact of sampling bias. A
      logistic regression analysis of data from 21 states finds that artists have 270%
      higher risk of suicide than nonartists. However, after controlling for gender and
      sociodemographic variables, this risk level is reduced to 125%. The findings are
      related to both psychiatric and work-related stress factors that may place
      artists at risk of suicide as an occupational group.

PMID- 9014268
TI  - Temperamental vulnerability and suicide risk after attempted suicide.
AB  - The aim was to extend recent findings of suggested temperamental features in
      attempted suicide and to explore possible domains of vulnerability to suicide
      risk after attempted suicide. Fifty-four psychiatric inpatients hospitalized
      after a suicide attempt underwent lumbar puncture for analysis of CSF 5-HIAA
      concentration and also completed the Karolinska Scales of Personality (KSP)
      before discharge from the hospital. Suicide attempters scored high on Somatic
      Anxiety, Psychic Anxiety, and Muscular Tension, and low on Socialization,
      findings that support recent findings in suicide attempters followed up after an
      emergency room visit. Five patients committed early suicide, i.e., within 3
      years, and the overall long-term suicide mortality after attempted suicide was
      13%. There were significant correlations between survival time among early
      suicides and CSF 5-HIAA (r = .87; p = .054), and the following KSP scale t
      scores: Somatic Anxiety (r = -.96; p < .05), Impulsivity ( r = -.88; p < .05),
      and Socialization (r = 90; p < .05). KSP Socialization showed correlations with
      CSF 5-HIAA (r = .89; p = .046) among the early suicides. Features of
      temperamental vulnerability to suicide risk after attempted suicide might involve
      anxiety proneness, impulsivity, low socialization, and low CSF 5-HIAA.

PMID- 9014269
TI  - Repetition of parasuicide: a predictive study.
AB  - Medically treated parasuicides in a Norwegian county were monitored for more than
      6 years, and variables predicting repetition of the parasuicide were identified.
      Numerous variables were found to be associated with repetition of the parasuicide
      when studied retrospectively. In prospective analyses of patients with no history
      of parasuicide, only sexual abuse (both sexes), alcohol abuse, and report of own
      psychiatric problems as the main concern at the time of the parasuicide (females
      only) were significant predictors of repetition. The results indicated that
      predictors of repetition are highly dependent upon the stage of the "suicidal
      career" the patients are in.

PMID- 9014270
TI  - The effect of marital integration on African American suicide.
AB  - Research on the impact of marital integration on suicide has neglected race
      specific analysis. Existing work has been marked by methodological problems and
      has thus found inconsistent results. The present paper is the first national
      study of the problem. In a logistic regression analysis of 2099 African American
      suicides and 1729 African American natural deaths, being divorced or widowed
      significantly raises the odds of death by suicide; being single does not. A
      parallel analysis for Whites finds greater support for a link between martial
      status and suicide. Marital status may be less important for African Americans in
      suicide prevention because extended family ties are stronger for African
      Americans than Whites.

PMID- 9014271
TI  - Temporal fluctuations in suicide calls to a crisis intervention service.
AB  - Suicide-related calls received by a crisis intervention center were analyzed for
      temporal variations. The overall number of calls, calls concerning personal
      suicidal ideation, and calls concerning third-person suicide attempt varied by
      both month and day of the week. Ideation calls and calls involving a suicide
      attempt varied by day of the month. Month and day of the week variation in third
      person calls paralleled variations in completed suicides. Fluctuations were large
      enough to be useful in scheduling crisis center staff. The possibility that third
      person calls represent a greater suicide threat than first-person calls is
      discussed.

PMID- 9014272
TI  - In conscience's talons: the suicide of a Vietnam veteran.

PMID- 9014273
TI  - Suggested recommendations for the study of suicide and other life-threatening
      behaviors.

PMID- 9014274
TI  - Strategies for conservative treatment of cervical ectopic pregnancy.

PMID- 9014275
TI  - Diagnosis and treatment of early cervical pregnancy: a review and a report of two
      cases treated conservatively.
AB  - We report two cases of cervical pregnancy which were diagnosed by ultrasound at 5
      and 8 weeks' gestation. In both cases a gestational sac was visualized below the
      internal os and color Doppler examination demonstrated peritrophoblastic blood
      flow characteristic of early implantation. Both patients were successfully
      treated with systemic methotrexate. Including these two cases, a total of 83
      early cervical pregnancies have been reported in the literature over the last 10
      years. Of these, 40 patients were primarily treated by conservative surgery, 40
      by non-surgical methods using methotrexate or potassium chloride, and the
      remaining three by other chemotherapeutic agents. The likelihood of being cured
      was similar in the surgical and non-surgical groups (odds ratio 1.1; 95%
      confidence interval 0.4-3.2). However, patients who were primarily treated by
      surgery were more likely to sustain major hemorrhage (odds ratio 8.0; 95%
      confidence interval 2.4-26.5) and to require hysterectomy (odds ratio 7.4; 95%
      confidence interval 0.9-63.8) than those treated medically. This indicates that
      non-surgical methods should be used for primary treatment of cervical pregnancy,
      while surgery should be reserved for those patients in whom medical therapy is
      not successful.

PMID- 9014276
TI  - Successful transvaginal ultrasound-guided puncture and injection of a cervical
      pregnancy in a patient with simultaneous intrauterine pregnancy and a history of
      a previous cervical pregnancy.
AB  - Cervical pregnancy is a rare type of ectopic pregnancy. A recurrent cervical
      pregnancy in conjunction with a viable intrauterine pregnancy is an even rarer
      event. We present a case in which a recurrent cervical pregnancy was treated by
      selective reduction using an injection of potassium chloride guided by
      transvaginal sonography. The intrauterine gestation was delivered at a gestation
      of 34 weeks and 4 days by Cesarean section. Subsequently, the patient was treated
      with intramuscular methotrexate with a prolonged, but complete, resolution of the
      cervical pregnancy.

PMID- 9014277
TI  - Fetal megacystis at 10-14 weeks of gestation.
AB  - During the study period, 24,492 pregnant women attended the Harris Birthright
      Research Centre at 10-14 weeks of gestation, at which time, in addition to the
      measurements of nuchal translucency thickness and crown-rump length (CRL), data
      on fetal abnormalities were recorded onto a computer database. Cases of
      megacystis were identified and the records were reviewed. Additionally, the
      relationship of the longitudinal bladder diameter with the CRL and the bladder
      diameter/CRL ratio (expressed as a percentage) were examined with the use of data
      from 300 normal fetuses at 10-14 weeks. Megacystis was present in 15 of the
      24,492 pregnancies (1 in 1,633) and in these cases the minimum longitudinal
      bladder diameter was 8 mm and the minimum bladder diameter/CRL ratio was 13%. In
      the 300 control fetuses the bladder was visualized in 278 (92.7%) of the cases
      and the longitudinal bladder diameter increased with the CRL (bladder diameter =
      0.065 x CRL - 0.69; r = 0.47, p < 0.001), none of the measurements was more than
      6 mm and the median bladder diameter/CRL ratio was 5.4% (range 0-10.4%) which did
      not change significantly with gestation (r = 0.1, p = 0.09). The bladder was
      visible in all cases with a minimum CRL of 67 mm. In three of the 15 cases with
      megacystis, there were chromosomal abnormalities. In the chromosomally normal
      group, there were seven cases with spontaneous resolution, whereas in four cases
      there was progression to severe obstructive uropathy. The bladder diameter was 8
      12 mm and the bladder diameter/CRL ratio 13-22% in all cases with resolution and
      in one case with progressive megacystis; in the other three cases with
      progressive obstruction, the bladder length was more than 16 mm and the bladder
      diameter/CRL ratio was more than 28%.

PMID- 9014278
TI  - Sonographic diagnosis of fetal upper extremity dysmorphology: significance and
      outcome.
AB  - The aim of this study was to determine the etiology, associated anomalies and
      outcome of fetuses with postural deformities and contractures of the upper
      extremities detected sonographically. Fifty-four fetuses with sonographically
      detected postural anomalies of the upper extremities were identified from our
      database. Sonographic findings and associated anomalies were tabulated on the
      basis of the original sonogram. Perinatal follow-up and/or karyotype were
      available in 52 cases from a review of the maternal and newborn medical records
      and pathology reports. Of the 52 fetuses with sonographically detected anomalies
      of the upper extremities, 44 (85%) were non-survivors and eight (15%) were
      survivors. Forty-three fetuses had associated sonographic abnormalities.
      Karyotyping performed in 44 cases revealed 26 cases (59%) of aneuploidy, with
      trisomy 18 accounting for 23/26 (88%). In the setting of a normal karyotype, a
      variety of genetic disorders were found, including syndromes involving the fetal
      dyskinesia/akinesia sequence. Disturbances in amniotic fluid occurred in 48% of
      the cases (24 fetuses with polyhydramnios and one with oligohydramnios). In
      conclusion, the sonographic detection of postural abnormalities of the upper
      extremities carries a guarded prognosis, with survival in 15% of fetuses and a
      high incidence of chromosomal defects.

PMID- 9014279
TI  - A comparative analysis of second-trimester ultrasound dating formulae in
      pregnancies conceived with artificial reproductive techniques.
AB  - A dataset of 64 pregnancies conceived by artificial reproductive techniques was
      studied to assess the accuracy of second-trimester dating formulae when these
      were applied in routine ultrasound clinics in different centers. Dating formulae
      for biparietal diameter (BPD) and femur length (FL) were derived for a
      gestational age range of 14-23 weeks. The best fit curves represented linear
      equations: gestational age (days) = 44.2 + 2 x BPD; and gestational age (days) =
      67.4 + 2.3 x FL. Twelve published formulae for biparietal diameter and femur
      length were reviewed and systematic and random errors were calculated for these
      formulae when they were applied to second-trimester scan measurements in
      precisely dated pregnancies. Overall, published dating formulae performed well in
      predicting gestational age. The 95% confidence interval was 8.3 days for
      biparietal diameter and 10.2 days for femur length. The study confirms the
      accuracy of ultrasound dating in routine ultrasound clinics and supports the use
      of ultrasound measurement alone in preference to menstrual history for dating
      pregnancy.

PMID- 9014280
TI  - Standards for the quantification of serial changes in the amniotic fluid index.
AB  - A total of 274 low-risk pregnancies underwent predetermined scheduled serial
      ultrasound examinations and measurements of the amniotic fluid index (AFI). As
      expected from previous cross-sectional studies, there is a gradual decline in the
      AFI from mid-trimester until term. The longitudinal nature of this data set
      permits the construction of conditional centiles for AFI whereby the AFI of an
      individual fetus at a given gestational age can be extrapolated to give a range
      of expected values for AFI (expressed as centiles) at a later gestational age.
      Examples of conditional centiles based upon 4-week measurement separations are
      presented. These conditional centiles permit the appropriate evaluation and
      quantification of time-dependent changes in AFI to be made.

PMID- 9014281
TI  - Indices of differential endometrial: myometrial growth may be used to improve the
      reliability of detecting endometrial neoplasia in women on tamoxifen.
AB  - The aim of this study was to test the hypothesis that the use of indices of
      differential endometrial: myometrial growth may be a non-invasive method of
      improving the reliability of detecting endometrial neoplasia in women on
      tamoxifen. Thirty postmenopausal women were involved in this prospective study.
      Nineteen had been treated with tamoxifen for 2 years or more, and eleven were age
      and ponderal index-matched controls who had never been exposed to tamoxifen and
      who were non-smokers. Transvaginal ultrasonography and color Doppler imaging were
      performed, to measure the length, anteroposterior diameter, uterine sagittal
      area, endometrial thickness and uterine blood flow (using the pulsatility index
      and the resistance index as measures of uterine blood flow impedance). The
      anteroposterior diameter: endometrial thickness ratio and product, and the
      saggital area: endometrial thickness ratio and product were used as indices of
      differential endometrial: myometrial growth. The predictive values (sensitivity,
      specificity, positive and negative predictive values) of each index were
      calculated using established criteria. For the purpose of analysis the women were
      allocated to three groups: controls (group 1); women on tamoxifen without
      endometrial neoplasia (group 2) and women on tamoxifen who developed endometrial
      neoplasia (group 3). The mean age was similar in the three groups as was the
      duration of tamoxifen treatment in groups 2 and 3. Analysis of the decision
      matrix based on increased endometrial thickness (> 5 mm) alone revealed good
      sensitivity (100%) and negative predictive value (100%) but poor specificity
      (46.15%) and positive predictive value (26.32%). However, when the indices of
      differential endometrial: myometrial growth were taken into consideration, the
      sensitivities and negative predictive values were similar but the specificities
      and positive predictive values were significantly improved, indicating an
      improvement in the reliability of predicting the development of endometrial
      neoplasia.

PMID- 9014282
TI  - The relationship between preoperative endometrial thickness, the anteroposterior
      diameter of the uterus and clinical outcome following transcervical resection of
      the endometrium.
AB  - The objective of this study was to identify whether the endometrial thickness, or
      the anteroposterior diameter of the uterus as assessed by transvaginal
      ultrasonography (TVS), could be used to predict the clinical outcome following
      transcervical resection of the endometrium (TCRE). An open observational trial
      was carried out, involving 195 consecutive patients undergoing TCRE, 188 of whom
      completed follow-up. The patients were examined by TVS preoperatively, and then 6
      weeks, 6 months and 1 year following TCRE. In all examinations, endometrial
      thickness, the anteroposterior diameter and residual endometrium, uterine
      morphology and the clinical outcome as measured by pain reduction, bleeding index
      and amenorrhea were assessed. Patients with a preoperative endometrial thickness
      of 8 mm or less had a higher rate of amenorrhea after 1 year than patients with
      an endometrial thickness exceeding 8 mm. Outcome did not relate to the
      histological phase of the endometrium obtained during resection. Neither the
      uterine anteroposterior diameter, or the presence of submucous fibroids, had any
      influence on the clinical outcome. Cavity fluid was observed in some cases but
      was not always associated with symptoms. Residual endometrium could be detected
      by TVS in 38% of the women after 1 year, but the vast majority of these patients
      reported a satisfactory outcome from the procedure. We conclude that the size of
      the anteroposterior diameter does not affect the clinical outcome of TCRE, whilst
      the preoperative endometrial thickness does have a significant impact on the
      likelihood of achieving amenorrhea after 1 year. The data suggest that TCRE
      should preferably be performed when the endometrium is at its thinnest and that
      there may be a useful role for agents that produce endometrial atrophy prior to
      surgery.

PMID- 9014283
TI  - Transvaginal power Doppler angiography of the fetal brain.
AB  - Using transvaginal B-mode sonography combined with power Doppler flow mapping on
      a total of 65 fetuses between 12 and 30 weeks of gestation, fetal intracerebral
      arteries and veins and blood flow were demonstrated in the coronal and sagittal
      planes. Clear images of the fetal brain and intracerebral vascular flow were
      obtained in 36 of the 65 cases. Bilateral vertebral arteries, the basilar artery
      and posterior cerebral arteries were imaged in the coronal plane at 12 weeks of
      gestation. Bilateral carotid and middle cerebral arteries were also depicted in
      the coronal plane at 13 weeks of gestation. The middle cerebral arteries and
      their branches were depicted via the anterior fontanelle in the coronal plane at
      20 weeks of gestation. The anterior cerebral artery and its branches were
      demonstrated in the sagittal plane at 26 weeks of gestation. The fetal cerebral
      venous systems of the superior sagittal sinus, internal cerebral vein, vein of
      Galen and straight sinus were clearly imaged in the mid-sagittal plane. Although
      we encountered several problems with this new technology of transvaginal power
      Doppler sonography, we were able to demonstrate its potential to assess fetal
      intracranial blood flow during pregnancy.

PMID- 9014284
TI  - Early prenatal diagnosis of oculoauriculovertebral dysplasia or the Goldenhar
      syndrome.
AB  - We report a case of the sonographic detection of oculoauriculovertebral dysplasia
      in a fetus at 15 weeks' gestation. An early diagnosis was suggested by
      observation of a maxillar cleft in association with unilateral microphthalmia. In
      the presence of microphthalmia the syndrome is likely to include mental
      retardation. When the diagnosis is made in the perinatal period, management
      generally involves cosmetic surgery. If, however, the condition is recognized in
      the early stages of gestation, termination of pregnancy may be an option.

PMID- 9014285
TI  - Prenatal diagnosis of type 2 Pfeiffer syndrome.
AB  - Pfeiffer syndrome is an autosomal dominantly inherited disorder consisting of
      craniosynostosis, a flattened midface with a beaked nose and ocular proptosis,
      and broad and medially deviated thumbs and great toes. Recently, based on
      clinical findings, the disorder has been divided into three subtypes: type 1,
      characterized by mild expression; type 2, in which clover leaf skull deformity
      and multiple congenital anomalies are present at birth; and type 3, which is
      similar to type 2, but lacks the presence of the clover leaf skull at birth. We
      describe a fetus in whom sonographic findings of clover leaf skull deformity,
      ocular hypertelorism, and varus deformity of the great toe led to the prenatal
      diagnosis of Pfeiffer syndrome type 2. We believe this is the second prenatal
      diagnosis of Pfeiffer syndrome, and the first time type 2 has been definitely
      identified in the second trimester of pregnancy.

PMID- 9014286
TI  - Endometrial fluid accumulation in postmenopausal women.

PMID- 9014287
TI  - The lambda sign in twin pregnancies.

PMID- 9014288
TI  - Construction and characterisation of a recombinant vaccinia virus expressing
      human papillomavirus proteins for immunotherapy of cervical cancer.
AB  - The presence and consistent expression of the genes encoding the human
      papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours
      presents the opportunity for an immunotherapeutic approach for control of the
      disease. This report describes the construction and characterisation of a
      recombinant vaccinia virus designed to express modified forms of the E6 and E7
      proteins from HPV16 and HPV18, the viruses most commonly associated with cervical
      cancer. The recombinant virus (designated TA-HPV) was based on the Wyeth vaccine
      strain of vaccinia, and was shown to express the desired gene products. Studies
      in mice indicated that the recombinant virus was less neurovirulent than the
      parental virus and was capable of inducing an HPV-specific CTL response. This pre
      clinical evaluation has provided a basis for the initiation of human trials in
      cervical cancer patients.

PMID- 9014289
TI  - Cytokine expression in the gut associated lymphoid tissue after oral
      administration of attenuated Salmonella vaccine strains.
AB  - The use of attenuated Salmonella vaccine vectors as delivery vehicles for
      heterologous antigens has been extensive. The majority of work has analyzed the
      specific immune responses to the recombinant antigen in question. In addition,
      most analysis has been performed on animals maintained with sterile food, water,
      and bedding. This report defines the Salmonella specific cytokine responses in
      the gut associated lymphoid tissue after oral immunization with two highly
      publicized attenuated Salmonella carrier strains in animals maintained with
      nonsterile food, water, and bedding. Increases in expression of both IL-4 and IFN
      gamma occur following immunization with either Salmonella construct. In addition,
      other cytokines (IL-6, IL-7, IL-12) increase at similar levels in either BRD509
      or KR1 dosed animals. Proinflammatory cytokines IL-1 and TNF-alpha are also
      present but unchanged at early time points (6, 24, and 72 hours), increasing only
      after 7 days postimmunization. These data have implications in the generation of
      immunity to recombinant antigens since the response to Salmonella will dictate
      the direction of responses in terms of CD4 T cell activation.

PMID- 9014290
TI  - Persistence of anti-HBs in children vaccinated against viral hepatitis B in the
      first year of life: follow-up at 5 and 10 years.
AB  - The persistence of anti-HBs protective levels in groups of children who had been
      immunized against Hepatitis B 5 and 10 years earlier, in their first year of
      life, has been studied. The results were analyzed according to the type of
      vaccine (both plasma-derived and DNA recombinant) and the number of doses
      administered (three or four doses). In addition, the protective effect of the
      vaccine in vaccinated subjects was studied in relation to the anti-HBc presence.
      The serologic results suggest that, in cohorts of children vaccinated 5 years
      earlier, a higher prevalence of subjects with anti-HBs protective levels was
      found, when the DNA recombinant vaccines were administered (97.6% for MSD
      Recombivax and 97.1% for SKF Engerix B); a lower one when the plasma-derived
      vaccine was used (80.4% Pasteur Merieux, Hevac B). Moreover, in cohorts of
      children vaccinated with plasma derived vaccine (hevac B) 10 years earlier, a
      higher prevalence of subjects with anti-HBs protective levels was demonstrated
      when four doses were administered (76.9%); a lower one when three doses were
      inoculated (57.5%). The absence of core antibody (anti-HBc) in responders to the
      vaccination shows the protective efficacy of both the DNA recombinant and plasma
      derived vaccines. On the other hand the presence of anti-HBc in some anti-HBs
      negative non-responders subjects shows the susceptibility of these people to
      infection. In anti-HBs negative vaccinated subjects the appearance of levels of
      anti-HBs in 95.9% of subjects, 1 week after the administration of a booster dose,
      demonstrates the presence of a solid immunologic memory.

PMID- 9014291
TI  - Safety study of the SAG2 rabies virus mutant in several non-target species with a
      view to its future use for the immunization of foxes in Europe.
AB  - The safety of the SAG2 virus, a low virulence mutant of the SAD strain, was
      investigated in ten species of mammals and seven species of birds liable to
      consume vaccine baits. These species are the western hedgehog (Erinaceus
      europaeus), the meadow vole (Microtus arvalis), the bank vole (Clethrionomys
      glareolus), the water vole (Arvicola terrestris), the field mouse (Apodemus
      flavicollis or A. sylvaticus), the Norway rat (Rattus norvegicus), the european
      badger (Meles meles), the domestic ferret (Mustela putorius furo), the wild boar
      (Sus scrofa), the domestic goat (Capra hircus), the carrion crow (Corvus corone),
      the rook (Corvus frugilegus), the buzzard (Buteo buteo), the red kite (Milvus
      milvus), the tawny owl (Strix aluco), the long-eared owl (Asio otus) and the barn
      owl (Tyto alba). The vaccine was administered orally to each species, by an
      intramuscular (i.m.) route to the rodents and ferret, and by an intracerebral
      route to the field mouse. No pathogenicity was observed in the 169 animals
      vaccinated throughout an observation period of over 30 days. After euthanasia, no
      rabies virus could be detected either in the brain or in the salivary glands of
      any of the animals. The SAG2 virus administered orally, triggered a specific
      seroconversion in the field mouse, wild boar, ferret and most of the raptors.
      Following administration by the i.m. route, specific antibody titres were
      observed in most of the rodents, as well as in the ferrets.

PMID- 9014292
TI  - Vaccination against feline leukaemia using a new feline herpesvirus type 1
      vector.
AB  - A recombinant feline herpesvirus type 1 (FHV-1) was constructed expressing the
      envelope glycoprotein gene from feline leukaemia virus (FeLV). The expression
      cassette containing the long terminal repeat promoter from Rous sarcoma virus was
      stably integrated at the locus downstream of the gC homologue in FHV-1. Oronasal
      vaccination with recombinant FHV-1 engendered significant protection against
      challenge with the homologous FelV-A/Glasgow-1 isolate. Three of four vaccinated
      cats did not become viraemic for FeLV and developed serum neutralizing antibodies
      while five of six controls became persistently infected after challenge. However,
      latent FeLV was detected at 12 weeks after challenge in bone marrow cultures of
      all animals except one. The potential of this new vector to protect against FeLV
      was compared with previous reports using live recombinant vaccines.

PMID- 9014293
TI  - Tagging a Vibrio cholerae El Tor candidate vaccine strain by disruption of its
      hemagglutinin/protease gene using a novel reporter enzyme: Clostridium
      thermocellum endoglucanase A.
AB  - The celA gene encoding Clostridium thermocellum endoglucanase A was expressed in
      Vibrio cholerae on its own promoter and used to tag a candidate El Tor biotype
      cholera vaccine strain. Colonies of the tagged strain could be unequivocally
      distinguished by overlaying them with CM-cellulose indicator agar and Congo Red
      staining. Expression of celA did not affect growth of V. cholerae in vitro and in
      vivo. The celA gene was inserted in the chromosomal hap locus encoding V.
      cholerae hemagglutinin/protease, a putative "detachase", to create a hap- mutant
      that could be identified and scored by its halo of cellulolytic activity. The
      inactivation of hap had a positive effect on colonization in the infant mice
      model. The above results indicate that celA is a suitable marker gene for V.
      cholerae and hap is an appropriate locus for insertion of foreign DNA in vaccine
      development. Inactivation of hap, by increasing the duration of adherence, might
      decrease excretion of the resulting vaccine vector strain and thus increase its
      immunogenicity.

PMID- 9014295
TI  - The use of oral dehydroepiandrosterone sulfate as an adjuvant in tetanus and
      influenza vaccination of the elderly.
AB  - Elderly individuals often exhibit a poorer immune response and shorter duration
      of immunity to vaccines than younger persons. Improvement in vaccine response has
      been demonstrated when administering the hormone dehydroepiandrosterone sulfate
      (DHEAS) as an adjuvant in animal trials. Two separate, randomized double-blinded
      vaccine trials were therefore conducted using DHEAS as an oral adjuvant in
      individuals age 65 or older. Sixty-six individuals were randomized to DHEAS, 50
      mg po bid for 4 days, or a placebo capsule. Tetanus vaccination was given
      immediately before the fifth dose. At entry the level of protective antibody was
      age-dependent (P = 0.009), and by 28 days post-vaccination most individuals had
      protective levels of antibody, with no difference noted between treatment groups.
      In the second study, 67 individuals received placebo capsules or DHEAS
      immediately before and 24 h after influenza vaccination. The number of
      individuals who developed protective titers (> or = 1:40) was not different in
      the two groups. The mean log increase in HAI response was greater in the DHEAS
      group to all three vaccine components, although this did not achieve
      significance. Minimal side-effects of DHEAS administration were noted. Given the
      trend toward improved response in the elderly to influenza, larger trials using
      DHEA as an adjuvant in vaccines that are neoantigens may be indicated.

PMID- 9014294
TI  - Synthetic peptides entrapped in microparticles can elicit cytotoxic T cell
      activity.
AB  - Peptides from Plasmodium berghei circumsporozoite protein (CS) and influenza A
      virus nucleoprotein (NP) were entrapped in microparticles prepared from poly
      (lactide-co-glycolide) polymers, and the microparticles were administered
      parenterally to mice. After immunization with single or multiple doses,
      splenocytes were tested for a cytotoxic T cell (CTL) response and high levels of
      CTL activity were detected. The CTL induced were CD8+, MHC class I restricted,
      and could recognize virus infected cells. Peptide entrapped in microparticles of
      mean size < 500 nm were better inducers of CTL than larger microparticles (mean >
      2 microns and above). Microparticles could also be used to deliver lipid modified
      peptides (lipopeptides) and elicited higher levels of cytolytic activity than
      either free peptide in microparticles or lipopeptide alone. Microparticles
      provide a novel way of inducing a CTL response using synthetic peptides.

PMID- 9014296
TI  - Mapping of protective and cross-reactive domains of the type A neurotoxin of
      Clostridium botulinum.
AB  - The purpose of this study was to identify the location of domains within the
      serotype A neurotoxin of Clostridium botulinum (BoNT/A) that conferred protection
      against botulism. The BoNT/A gene was subcloned into a series of 10 overlapping
      fragments that were expressed in Escherichia coli. The expressed proteins were
      partially purified and used to immunize mice. The resulting antisera were
      screened by immunoblotting analysis for the presence of BoNT/A-specific antibody.
      All fragments, except one, elicited antibody that recognized BoNT/A in an
      immunoblot. Serological screening identified several fragment-specific cross
      reactive epitopes that were shared by heterologous serotypes of BoNT. Most of
      these epitopes immunoreactive by enzyme-linked immunosorbent assay, but not by
      immunoblot. Only two fragments were shown to confer protection against BoNT/A
      intoxication. Both of these proteins were derived from segments of the heavy
      chain and encoded amino acid residues H455-661 and H1150-1289 of BoNT/A.

PMID- 9014297
TI  - Construction and oral immunogenicity of a Salmonella typhimurium strain
      expressing a streptococcal adhesin linked to the A2/B subunits of cholera toxin.
AB  - A major adhesin from the oral pathogen Streptococcus mutans has been shown to be
      mucosally immunogenic upon genetic fusion with the cholera toxin A2/B subunits.
      To take advantage of the ability of Salmonella typhimurium to deliver cloned
      antigens to the mucosal inductive sites that would obviate the need for antigen
      purification, we expressed this chimeric construct in an attenuated S.
      typhimurium strain under the control of bacteriophage T7 transcription. Residual
      expression of the temperature-regulated T7 RNA polymerase at 30 degrees C allowed
      production of the chimeric protein at 2-3% of the total soluble protein, but it
      was increased five to six times following induction at 37 degrees C. Oral
      administration of a single dose of 10(9) recombinant Salmonella to mice resulted
      in serum IgG and salivary IgA antibody responses to Salmonella, cholera toxin,
      and the streptococcal adhesin, which were generally enhanced after a booster
      immunization.

PMID- 9014299
TI  - Preparation and characterization of immunostimulating complexes (ISCOMs) of
      Japanese encephalitis virus.
AB  - ISCOMs (immunostimulating complexes) were prepared from envelope glycoprotein
      (Egp) of Japanese encephalitis (JE) virus. ISCOMs showed a single band of the
      viral Egp in SDS-PAGE, which reacted with polyclonal and monoclonal antibody
      (MAb) raised against Egp. Comparison between the epitopes exposed on JE virion
      and JE ISCOMs, by antigen capture ELISA, utilizing a panel of domain-specific
      MAbs, revealed identical epitopes exposed on the Egp incorporated in ISCOMs and
      the whole virion. Electron micrographs of ISCOMs showed spherical cage-like
      structures of 35 nm. ISCOMs with Egp were good immunogenes, which stimulated high
      titres of neutralizing antibodies, both in mice and rabbits.

PMID- 9014298
TI  - Immune response to tissue culture rabies vaccine in subjects who had previous
      postexposure treatment with Semple or suckling mouse brain vaccine.
AB  - Nerve tissue derived Semple and suckling mouse brain rabies vaccines are still
      widely used. Patients who experience a new rabies exposure and who were given
      such vaccines decades earlier are not uncommon in rabies endemic countries. The
      World Health Organization recommends that persons who have had a previous course
      of a potent tissue or avian culture rabies vaccine and are reexposed, be given
      booster infections on days 0 and 3 without rabies immune globulin. Persons who
      have had previous pre- or postexposure vaccination with a vaccine of unproven
      potency, should receive a full course of tissue or avian cell vaccine and immune
      globulin in the event of a new exposure. This study evaluated the immune response
      in 98 Thai patients who gave a history of rabies postexposure treatment with
      Semple or suckling mouse brain vaccines 10-50 years previously. The majority (81)
      had an anamnestic response and developed neutralizing antibodies that were above
      the recommended minimal acceptable level (0.5 IU ml-1) on day 7. This suggests
      that they still had immunological memory. A minority of 18% had antibody titers
      below this level on day 7. However, they all developed titers above 0.5 IU ml-1
      on days 14 and 30. Failure to have an accelerated response to revaccination by
      day 7 did not appear to be related to age or time elapsed since previous nerve
      tissue derived vaccine administration. It was not possible to predict which
      subject will or will not have an acceptable level of antibody before day 14.
      Rabies exposed patients who give a prior history of vaccination with an unknown
      or nerve tissue derived vaccine should therefore be treated as if they had never
      been vaccinated.

PMID- 9014301
TI  - The influence of age on the canine immune system.
AB  - Immune function was assessed in a group of 47 Labrador Retrievers, ranging in age
      from 0.8 to 11.5 years, in order to establish baseline data on canine
      immunosenescence. Natural killer cell activity, lymphocyte subset distributions,
      antibody production, and mitogen-induced lymphoproliferative responses, all of
      which have been demonstrated to undergo age-related changes in humans and mice,
      were chosen as indicators of immune function. Dogs were categorized by age as
      young (mean 2.4 years), middle-aged (mean 5.8 years), and old (mean 9.1 years).
      Natural killer cell activity was not affected significantly by age. Lymphocyte
      subset analysis revealed a significant age-related increase in the percentage of
      cells staining with a pan T-cell reagent, accompanied by a corresponding increase
      in the percentage of CD8 cells from youth to middle age. An age-related decrease
      in the percentage of B-cells was observed concomitant with the increases in T
      cell percentages. A gender-related difference in pan T-cell distribution was also
      observed, with females having a higher percentage than males. Lymphoproliferative
      responses of both young and middle-aged dogs to the mitogens concanavalin A,
      phytohemagglutinin, pokeweed mitogen, and staphylococcal enterotoxin B were
      significantly higher than those of old dogs. In general, the mitogen responses of
      male dogs were affected more dramatically by age than those of females. A
      significant age-related decline in in vivo antibody responses to the protein
      antigen, keyhole limpet hemocyanin, was not observed, although the mean titers of
      the young dogs were higher than those of the old.

PMID- 9014300
TI  - Immunogenicity of a fusion protein linking the beta subunit carboxyl terminal
      peptide (CTP) of human chorionic gonadotropin to the B subunit of Escherichia
      coli heat-labile enterotoxin (LTB).
AB  - Human chorionic gonadotropin (hCG) is currently under investigation as an
      antigenic target in both anti-cancer and anti-fertility vaccines. Formulations
      studied to date show promise in clinical trials for both applications yet are
      expensive to produce and require frequented administration in order to maintain
      an effective antibody titer. We have engineered a fusion protein consisting of
      Escherichia coli heat-labile enterotoxin subunit B (LTB) genetically linked at
      its C terminus via a nine amino acid linker to the 37 amino acid carboxyl
      terminal peptide (CTP) of the hCG beta chain. This LTB-CTP fusion protein is
      stably expressed in bacteria and forms pentamers of full-length protein subunits.
      Purified LTB-CTP protein hCG-specific antibodies in mice without additional
      adjuvants.

PMID- 9014302
TI  - A new colorimetric method for measuring cell-mediated cytotoxicity in dogs.
AB  - In order to replace the radioactive 51chromium release assay (CRA), a
      colorimetric method for the determination of cell-mediated cytotoxicity of
      natural killer (NK) effector cells of dogs and adherent target cells was
      developed using the dye Rose Bengal (RB). After a 14 h incubation period of
      leucocytes isolated from the peripheral blood (PBL) of dogs and a natural killer
      cell-sensitive canine adenocarcinoma cell line (CTAC), effector and lysed target
      cells were removed by washing, and the surviving adherent target cells were
      stained with RB. The optical density (OD) of the remaining target cells was
      measured in a microspectrophotometer (ELISA reader) and was found to correspond
      to the number of surviving cells, and thus was inversely correlated to the
      cytotoxic activity. The RB assay revealed almost identical cytotoxic values when
      compared with the CRA. In contrast to this assay the RBA is quick and easy to
      perform, inexpensive and avoids radioactive materials and waste. However, the
      method is restricted to adherent target cells.

PMID- 9014303
TI  - Feline ocular and cerebrospinal fluid Toxoplasma gondii-specific humoral immune
      responses following specific and nonspecific immune stimulation.
AB  - Toxoplasma gondii-naive cats and cats previously infected orally with T. gondii
      tissue cysts were inoculated with soluble tachyzoite antigens plus adjuvant or
      adjuvant alone. Toxoplasma gondii-specific IgM and IgG were measured in serum,
      aqueous humor, and cerebrospinal fluid (CSF). The Goldman-Witmer coefficient (C
      value) for ocular or central nervous system (CNS) antibody production was
      calculated for aqueous humor or CSF samples positive for T. gondii-specific
      antibodies. Following inoculation with adjuvant plus soluble tachyzoite antigens,
      ocular and CNS T. gondii-specific IgG C values increased in the three previously
      infected cats. Following inoculation with adjuvant, the two previously infected
      cats had increases in ocular and CNS T. gondii-specific IgG C values. Ocular (2/3
      cats) or CNS (1/3 cats) T. gondii-specific IgG C values of over 1 were detected
      in some T. gondii-naive cats following inoculation with adjuvant plus soluble
      tachyzoite antigens. The results of this study suggest that T. gondii-specific
      IgG C values of over 1 in aqueous humor or CSF do not prove active ocular or CNS
      infection in all cats.

PMID- 9014304
TI  - Separation of equine IgG subclasses (IgGa, IgGb and IgG(T)) using their
      differential binding characteristics for staphylococcal protein A and
      streptococcal protein G.
AB  - Equine IgG possesses four well-defined subisotypes, designated IgGa, IgGb, IgGc
      and IgG(T) on the basis of their increasing anodal mobility in electrophoresis.
      However, the preparation of IgGa and IgGb reference proteins has not previously
      been reported. Certain bacterial cell wall proteins, termed protein A and protein
      G, have been used for purification of IgG subisotypes from the serum of domestic
      animals which, combined with other techniques utilising differences in the
      physico-chemical properties of the proteins, has allowed the purification of Ig
      isotypes. This paper describes purification of the subisotypes of equine IgG.
      Purification of IgGa and IgGb was achieved by the separation of a 'fall-through'
      peak from ion-exchange chromatography consisting of IgGa and IgGb into two
      fractions (peaks C and D) by FPLC protein A and protein G affinity
      chromatography. Peak C consisted of IgGb and peak D consisted of IgGa exhibiting
      slightly faster cathodal migration than peak C in IEP analysis. Affinity
      chromatography using protein A and G columns also indicated that there may be two
      different components of IgG(T); one with a low affinity for protein G and the
      other having a greater affinity for protein G.

PMID- 9014305
TI  - Assessment of bovine mononuclear phagocytes and neutrophils for induced L
      arginine-dependent nitric oxide production.
AB  - Microbicidal activity of reactive oxygen intermediates and reactive nitrogen
      intermediates has been described from both murine and human cytokine activated
      macrophages. An L-arginine-dependent pathway of nitric oxide generation has
      recently been described from bovine bone marrow-derived and monocyte-derived
      macrophages in response to a phagocytic stimulus. We have investigated the
      induction and release of both reactive oxygen intermediates and reactive nitrogen
      intermediates from bovine neutrophils, and blood and spleen mononuclear
      phagocytes in response to either a phagocytic or cytokine stimulus. Mononuclear
      phagocytes were poor producers of hydrogen peroxide (a measure of reactive oxygen
      intermediate production) under conditions that readily caused release by
      neutrophils. In contrast, nitrite, as a measure of nitric oxide production, could
      not be induced from neutrophils under any stimulation conditions, while
      mononuclear phagocytes responded to both a phagocytic stimulus and cytokines with
      the induction of nitric oxide synthase message and production of nitric oxide.
      There appeared to be two populations of monocytes that differed both in their
      adherent characteristics and their level of cytokine-induced nitric oxide
      production. Both populations stained with a single monoclonal antibody. However,
      the population that had not adhered to plastic within 3 h responded to cytokine
      stimulation, producing up to 3 times more nitric oxide on a per cell basis than
      the readily adherent population. Cytokine induction required the presence of
      interferon-gamma and either tumor necrosis factor-alpha or lipopolysaccharide. L
      arginine dependence was demonstrated by inhibition with an L-arginine analog and
      restoration with addition of excess L-arginine.

PMID- 9014306
TI  - B-1a, B-1b and conventional B cell lymphoma from enzootic bovine leukosis.
AB  - In order to characterize the phenotypes of tumor cells and to clarify from which
      B cell lineage the lymphomas were derived, ten cows with enzootic bovine leukosis
      were examined by means of immunohistologic staining and flow cytometry. The tumor
      cells expressed mainly major histocompatibility complex (MHC) class II+ (10/10),
      BoCD11b+ (9/10), IgG1+ (8/10), B-B2+ (8/10) BoCD5+ (7/10), and lambda light
      chain+ (7/10). Tumor cells from only one animal expressed sIgM+ (1/10). Tumor
      cells from all ten animals were negative for IgG2, BoCD3, BoCD4, BoCD8, WC1-N2,
      and IL-2R alpha. The phenotypes of these tumor cells were all slightly different,
      suggesting that bovine leukemia virus (BLV)-induced lymphoma expresses phenotypic
      diversity. Moreover, tumor cells from seven cattle coexpressed BoCD5 and BoCD11b
      (B-1a cells). On the other hand, tumor cells from two of them only expressed
      BoCD11b (B-1b cells), and those from one were negative for both BoCD5 and BoCD11b
      (conventional B cells). Therefore, we concluded that BLV-induced lymphoma cells
      can be derived from B-1a, B-1b and conventional B cells.

PMID- 9014307
TI  - Effects of BHV-1 on PMN adhesion to bovine lung endothelial cells.
AB  - Bovine herpes virus-1 (BHV-1) infection appears to decrease the rate of
      polymorphonuclear leukocyte (PMN) influx into the lung in response to the
      secondary invader, Pasteurella haemolytica. It was postulated that BHV-1 may
      affect the rate of cellular infiltration by altering the function of the
      endothelium, thereby preventing PMN movement across the blood-tissue barrier.
      Therefore, we decided to investigate the effect of BHV-1 on the ability of PMN to
      adhere to lung endothelial cells (LEC). LEC were isolated from fetal bovine fetal
      tissue and were shown to function in PMN adhesion assays. Furthermore, enhanced
      PMN adhesion was observed after exposure of LEC to recombinant bovine TNF-alpha
      (rBoTNF-alpha) for 4, 8, 12, and 24 h. LEC infected with BHV-1 were shown to be
      less responsive to rBoTNF-alpha. However, infection of LEC with BHV-1 at an
      multiplicity of infection (MOI) of 1.0 or 10 did not affect basal levels of PMN
      adhesion to these cells. Decreased PMN binding to BHV-1-infected LEC,
      simultaneously treated with rBoTNF-alpha, was observed at 10-12 h post-infection.
      The data suggest that BHV-1 may prevent cytokine-induced PMN infiltration of the
      lung through the modification of EC responses to cytokines.

PMID- 9014308
TI  - Within day and between day variation of the in vitro under agarose chemotaxis
      assay in bovine.
AB  - The present study was conducted to determine within day variation (experiment I)
      and between day variation (experiment II) of the in vitro under agarose
      chemotaxis assay. Further, results from experiment II were used to estimate a
      more stable immunological parameter for the chemotactic activity. In experiment
      I, blood samples of eight cows were taken every 4 h starting at 0800 during a 24
      h period. This procedure was replicated on three different days with peripheral
      white blood cells of lactating bovine. Chemotactic differential showed variation
      within a day. The differences between samplings were not constant over the days,
      but varied randomly from day to day. In experiment II, 12 cows were followed for
      8 consecutive days and blood samples for chemotaxis assay were taken once a day
      at 0730. Differences between the days were significant. With a conditional auto
      regression model of the first order adjusted least squares means of each cow were
      estimated over the 8 consecutive days. The chemotactic value of a day was used to
      estimate the value of the next day. Expanding the model with more previous days
      did not improve the model. The results of this study indicate that blood samples
      for chemotaxis should be taken at the same time of the day to control for within
      day variation. If a sequence of chemotactic values is available we strongly
      suggest working with adjusted least square means of chemotactic differentials.
      These adjusted means show less random variation and are a more stable parameter
      for chemotactic activity.

PMID- 9014309
TI  - Experimental mucosal disease in cattle: changes in the number of lymphocytes and
      plasma cells in the mucosa of the small and large intestine.
AB  - Changes in the number of lymphocyte and plasma cell subtypes were investigated in
      the lamina propria and in the epithelium of the small and large intestine of
      cattle with mucosal disease. Mucosal disease had been induced experimentally in
      seven out of 13 animals persistently viremic with non cytopathogenic BVD-virus by
      inoculation with a matching cytopathogenic BVD-virus. For comparison, six
      clinically healthy, persistently viremic cattle were used. IgA+, IgM+ and IgG1+
      plasma cells, BoCD4+, BoCD8+ and gamma delta + T-lymphocytes, and the antigen of
      the cytopathogenic BVD-virus were demonstrated in tissue sections by
      immunohistochemistry. Distribution of cellular subtypes in the controls was
      consistent with data reported from non infected cattle. In cattle with mucosal
      disease, a decrease in the number of plasma cells which was significant for IgA+
      and IgM+, but not for IgG1+ plasma cells was found in the lamina propria. The
      number of BoCD4+ T-lymphocytes was reduced in the small intestine, whereas their
      number per mm2 of mucosa was increased in the large intestine. Numbers of
      intraepithelial BoCD8+ and gamma delta + T-lymphocytes were severely decreased.
      Antigen of the cytopathogenic BVD-virus was detected predominantly in epithelial
      cells of the crypts. Overall there is a severe loss of effector cells which are
      essential components of the humoral and cell mediated immune protection of the
      mucosal barrier. The decrease of immunoregulatory cells in the lamina propria and
      epithelium may contribute to the transformation of mucosal architecture in
      mucosal disease.

PMID- 9014310
TI  - Recognition of ovine lentivirus gag gene products by serum from infected sheep.
AB  - In order to localize the immunodominant regions, 12 ovine lentivirus (OLV) gag
      coding gene fragments were cloned and expressed in Escherichia coli and then
      tested in a Western blot (WB) assay against a panel of sera collected from US and
      Italian OLV-infected sheep. The most immunoreactive regions were mapped to the
      amino-terminal of p25 and carboxyl-terminal of p14. In addition, we found that
      the reactivity pattern between US and Italian sheep was very similar, suggesting
      the antigenic domain between US and Italian isolates in the gag gene structures
      could be conserved. Given the broad immunoreactivity of the amino-terminal of
      p25, this region could serve as an ideal diagnostic antigen for the serological
      identification of OLV-infected sheep.

PMID- 9014311
TI  - Early pulmonary cell response during experimental maedi-visna virus infection.
AB  - A model of experimental infection with EV1, a British isolate of maedi-visna
      virus (MVV), has been developed. Twelve male Texel sheep were allocated to three
      groups and inoculated by the respiratory route with different inocula. Six of the
      animals received 10(7.2) tissue culture infective dose (TCID50) of MVV EV1
      strain. Two sheep were inoculated with the same dose of heat inactivated MVV EV1
      strain. An additional group of four sheep was sham-inoculated with identically
      prepared virus-free culture media. Experimental infection was followed for 16
      weeks. Prior to inoculation, routine haematology, bronchoalveolar lavage (BAL)
      and flow cytometric analysis of bronchoalveolar lavage fluid (BALF) lymphocytes
      were performed in all animals to provide baseline parameters. Flow cytometric
      analysis of BALF lymphocytes and differential BALF cell counts were performed.
      Precipitating antibodies to MVV developed in all MVV-inoculated animals during
      the first 4 weeks post-inoculation, while the rest remained seronegative to MVV.
      MVV-infected animals had significantly decreased (P < 0.05) percentages of
      macrophages and significantly increased (P < 0.05) percentages of lymphocytes in
      BALF 4 weeks post-inoculation. Phenotypic changes in BALF T lymphocytes from MVV
      inoculated animals, compared with the other two groups, showed significantly
      decreased (P < 0.05) percentages of CD4+ and gamma delta + T lymphocytes,
      significantly increased (P < 0.05) percentages of CD8+ lymphocytes and
      significant inversion (P < 0.05) of the CD4+/CD8+ ratio at different sampling
      times, but between 2 and 12 weeks post-inoculation. These findings indicate that
      during experimental MVV-infection an early, short-term cellular reaction occurs
      in the lung, that is characterised by T lymphocyte phenotypic changes that are
      very similar, if not identical, to those observed in natural MVV infection.

PMID- 9014312
TI  - Mimicry of a 21.5 kDa myelin basic protein peptide by a Maedi Visna virus
      polymerase peptide does not contribute to the pathogenesis of encephalitis in
      sheep.
AB  - Epitope mimicry is the theory that an infectious agent such as a virus causes
      pathological effects via mimicry of host proteins and thus elicits a cross
      reactive immune response to host tissues. Weise and Carnegie (1988) found a
      region of sequence similarity between the pol gene of the Maedi Visna virus
      (MVV), which induces demyelinating encephalitis in sheep, and myelin basic
      protein (MBP), which is known to induce experimental allergic encephalitis (EAE)
      in laboratory animals. In this study, cross-reactions between sera raised in
      sheep against synthetic peptides of MVV (TGKIPWILLPGR) and 21.5 kDa MBP
      (SGKVPWLKPGR) were demonstrated using enzyme-linked immunosorbant assay (ELISA)
      and thin layer chromatography (TLC) immunoprobing. The antibody responses of MVV
      infected sheep were investigated using ELISA against the peptides, and MBP
      protein, immunoprobing of the peptides on TLC plates and Western blotting against
      MBP. Slight significant reactions to the 21.5 kDa MBP peptide (P < 0.001) and to
      a lesser extent sheep MBP (P < 0.004) were detected in ELISA. The MBP peptide
      evoked stronger responses from more sera than the MVV peptide on immunoprobed TLC
      plates. On the Western blots, eight of the 23 sheep with Visna had serum
      reactivity to MBP. This slight reaction to MBP in MVV-infected sheep is of
      interest because of the immune responses to MBP evident in multiple sclerosis and
      EAE, but its relevance in Visna is limited since no correlation with disease
      severity was observed. The cell-mediated immune responses of MVV-infected sheep
      against similar peptides was assessed. The peptides did not stimulate
      proliferation of peripheral blood lymphocytes of MVV-infected sheep. Since the
      MVV peptide was not recognised by antibodies or T lymphocytes from MVV-infected
      and encephalic sheep, it was concluded that epitope mimicry of this 21.5 kDa MBP
      peptide by the similar MVV pol peptide was not contributing to the
      immunopathogensis of Visna. The slight antibody response to MBP and the MBP
      peptide can be attributed to by-stander effects of the immunopathology of MVV
      induced encephalitis.

PMID- 9014313
TI  - Immunisation regimes used to elevate serum IgE in sheep.
AB  - Six different immunisation regimes were used in an attempt to elevate the
      concentration of ovine IgE. The response was measured by a passive cutaneous
      anaphylaxis (PCA) test. These regimes included infection with Ascaris suum and
      the combination of infection and parenteral administration of Ascaris antigens
      and ovalbumin in adjuvants. The regime producing the highest titre of IgE was the
      combination of Ascaris infection with parenteral administration of Ascaris
      extract in Bordetella pertussis. This regime consistently produced a transient
      high titre (1:1280-1:2560) of serum IgE 9-12 days after immunisation. The
      response to ovalbumin was transient and the maximum PCA titre obtained was 1:10.

PMID- 9014314
TI  - The effect of cobalt supplementation on the immune response in vitamin B12
      deficient Texel lambs.
AB  - The effect of cobalt supplementation on the immune reactivity in vitamin B12
      deficient lambs was measured by comparing the humoral and cell-mediated immune
      responses against bovine herpes virus type 1 and Mycobacterium paratuberculosis.
      In addition, faecal egg counts were performed after natural infection with
      gastrointestinal nematodes. The experiments were performed with registered Texel
      twin lambs of the same sex. One lamb of each twin received three cobalt pellets
      divided over the grazing period. The non-supplemented lambs had lower serum
      vitamin B12 levels than their supplemented brother or sister. Our results
      demonstrate significantly lower lymphoblastic responses against Mycobacterium
      paratuberculosis in non-supplemented lambs compared with supplemented lambs 4
      weeks after paratuberculosis vaccination. Vitamin B12 deficient lambs in this
      study had significant higher faecal egg counts than their supplemented brother or
      sister after natural infection with gastrointestinal nematodes. No differences
      were found in total and differential white blood cell counts, in total protein,
      albumin, alpha-, beta- and gamma-globulin and in antibody production against
      bovine herpes virus type 1 and Mycobacterium paratuberculosis.

PMID- 9014315
TI  - Differential synthesis, cellular localisation and secretion of interleukin-1
      alpha interleukin-1 beta from ovine macrophages.
AB  - In order to characterise the regulatory processes involved in expression of
      ruminant interleukin 1 (IL-1) biological activity, we have used specific
      monoclonal antibodies to assess synthesis, cellular localisation and secretion of
      ovine IL-1 alpha and IL-1 beta from alveolar macrophages. Immunoprecipitation of
      IL-1 alpha and IL-1 beta from lysates of macrophages cultured in media alone or
      media supplemented with lipopolysaccharide (LPS) revealed that both forms of IL-1
      were synthesised as precursor proteins of 31-33 kDa. In contrast, both IL-1
      species were immunoprecipitated from culture supernatants as 17 kDa molecules.
      Comparison of the precipitated bands from culture supernatants suggested that
      significantly more IL-1 beta than IL-1 alpha was secreted by the macrophages.
      Flow cytometric analysis of IL-1 alpha and IL-1 beta expression by fresh
      unstimulated macrophages and macrophages cultured for 5 h with LPS demonstrated
      that a proportion of the cell associated IL-1 alpha, but not IL-1 beta, in
      stimulated macrophages was expressed at the cell surface. Analysis of IL-1
      secretion by cultured alveolar macrophages, using IL-1 alpha and IL-1 beta
      specific immunoassays, confirmed that IL-1 beta was the predominant secreted
      species of IL-1. While cell associated IL-1 alpha and IL-1 beta were detected by
      immunoprecipitation and flow cytometric analysis of macrophages cultured in media
      alone or media supplemented with LPS, secreted IL-1 beta was detected only after
      stimulation of macrophages with LPS. This indicates a dissociation of IL-1 beta
      synthesis and secretion and is indicative of an IL-1 beta converting enzyme
      similar to that which has been described in the human and mouse models.

PMID- 9014316
TI  - Phenotypic characterisation of intestinal lymphocytes in ovine paratuberculosis
      by immunohistochemistry.
AB  - Characterisation of the T-cell subsets in intestinal lesions in sheep with
      paratuberculosis may contribute to our understanding of the pathogenesis of this
      disease. To determine the phenotype and distribution of lymphocytes in the normal
      sheep intestinal mucosa and in Mycobacterium avium subspecies paratuberculosis
      infected sheep, immunohistochemistry was performed on 12 normal sheep and 18
      naturally infected, clinically diseased sheep of which 12 showed lepromatous and
      six tuberculoid forms of the disease. Immunoperoxidase staining was carried out
      on frozen sections of ileum using monoclonal antibodies against ovine CD4, CD8,
      and gamma delta T-cell receptor (TCR) markers. In all three sample groups, cells
      appeared to be non-randomly distributed throughout the lamina propria. Higher
      densities of lymphocytes were present in villus than in crypt areas. CD8+ cells
      were located principally around the epithelial basement membrane, whereas CD4+
      cells were localised towards the central villus area of the lamina propria.
      Lymphocytes bearing the gamma delta T-cell receptor were more widely distributed,
      both in epithelial and lamina propria compartments. Ileum with tuberculoid
      lesions had higher densities of CD4 and gamma delta T-cell subsets while
      lepromatous lesions had lower densities of CD4 and CD8 cells compared with normal
      tissues. The median relative percentage of CD4+ cells was increased and that of
      CD8+ cells decreased in tuberculoid cases, with a corresponding increase in the
      CD4:CD8 ratio, while the relative percentage of gamma delta + cells was increased
      in lepromatous cases.

PMID- 9014317
TI  - Immunophenotypic characterization of tumor infiltrating lymphocytes and
      peripheral blood lymphocytes isolated from melanomatous and non-melanomatous
      Sinclair miniature swine.
AB  - Selectively-bred Sinclair miniature swine exhibit a high incidence of congenital
      malignant melanoma which either proves fatal (10-15% of tumor-bearing piglets) or
      spontaneously regresses with a biphasic immunological phenomenon (85-90%) and no
      recurrence of malignancy. Mononuclear leukocytes were isolated from cutaneous
      melanomas and peripheral blood specimens collected from melanomatous (tumor
      bearing) Sinclair swine during second-phase regression, and from peripheral blood
      specimens collected from non-melanomatous (tumor-free) Sinclair swine and control
      Hanford swine. Leukocyte identities were determined with single- and dual
      parameter indirect immunofluorescence assays via flow cytometry. Assays for the
      specific surface antigens CD45, CD2, CD4, CD8, CD1, MHC class II, and N1 were
      employed to develop immunophenotypic profiles within the gated lymphocyte
      clusters from each TIL and PBL suspension. Significantly more CD8+ T-lymphocytes
      were identified in TIL suspensions than in peripheral blood leukocyte (PBL)
      suspensions (P < and = 0.05), regardless of breed or tumor status. Conversely,
      PBL suspensions contained significantly higher percentages of CD4+ T-lymphocytes
      than the levels found in TIL suspensions (P < and = 0.05). Virtually all TIL were
      MHC class II+, whereas the percentages of PBL expressing this antigen were
      markedly lower (P < and = 0.05). The percentages of T-lymphocytes co-expressing
      CD4 and CD8, a normal subset unique to swine, were generally consistent in all
      TIL and PBL suspensions examined. The results of this study have firmly
      established the immunophenotypic identities of cells associated with the second
      phase regression phenomenon of this melanoma and have identified specific
      variations in the leukocyte profiles of the respective TIL and PBL suspensions.

PMID- 9014318
TI  - Lectin-carbohydrate interaction in the immune system.
AB  - The immune system consists of various types of cells and molecules that
      specifically interact with each other to initiate the host defense mechanism.
      Recent studies have shown that carbohydrates and lectins (carbohydrate-binding
      proteins) play an essential role in mediating such interactions. Both lectins and
      carbohydrates are widely distributed in the mammalian tissues as well as in
      microorganisms. Carbohydrates, due to their chemical nature, can potentially form
      structures that are more variable than proteins and nucleic acids. Lectins can
      exist in either soluble or cell-associated form, and although overall structures
      vary, invariably possess carbohydrate-recognition domains (CRD) with various
      specificities. The interaction between lectins and carbohydrates have been shown
      to be involved in such activities as opsonization of microorganisms,
      phagocytosis, cell adhesion and migration, cell activation and differentiation,
      and apoptosis. The number of lectins identified in the immune system is
      increasing at a rapid pace. The development in this area has opened a new aspect
      in studying the immune system, and at the same time, provided new therapeutic
      routes for the treatment and prevention of disease.

PMID- 9014319
TI  - Identification of chicken Bu-1 alloantigens using the monoclonal antibody AV20.
AB  - The genetically polymorphic chicken antigen Bu-1 (chB6) has been identified by
      alloantisera raised against RPL line 6(3) (Bu-1a) and line 7(2) (Bu-1b) birds and
      subsequently by monoclonal antibodies (mAbs) which identify individual
      alloantigens. We have produced a monoclonal antibody, AV20, which recognises a
      monomorphic determinant on the antigen Bu-1. AV20 identifies a marker on both
      bursal and peripheral B cells. Staining characteristics on bursa, spleen, thymus
      and peripheral blood lymphocytes are similar to those of the allotypic antibodies
      which identify Bu-1a and Bu-1b. However, AV20 identified B cells in partially
      inbred birds as well as inbred lines including line 6(1) and line 7(2),
      indicating that it recognises a monomorphic determinant, AV20 immunoprecipitated
      an antigen with a Mwr of 150 kDa under non-reducing conditions and 70-75 kDa
      under reducing conditions indicating it is a homodimer. Serial
      immunoprecipitations or bursal-cell lysates from line 6(1) or line 7(2) confirmed
      that AV20 recognised the same antigen as mAbs against Bu-1a and Bu-1b in the
      respective lines.

PMID- 9014320
TI  - The humoral immune response of turbot, Scophthalmus maximus L., to spore-surface
      antigens of microsporidian parasites.
AB  - Experiments based on enzyme-linked immunosorbent assay (ELISA) revealed
      considerable antigenic homology in turbot between two species of microsporidian,
      Tetramicra brevifilum (a parasite of the turbot, Scophthalmus maximus) and Glugea
      caulleryi (a parasite of the lesser sand-eel, Ammodytes tobianus). We next
      investigated whether G. caulleryi is able to suppress the turbot immune response.
      Intraperitoneal inoculation of turbot with G. caulleryi spores (whether heat
      killed or viable) did not suppress the humoral immune response to injection of G.
      caulleryi spores plus adjuvant 15 days later; in fact, specific serum antibody
      levels (as revealed by ELISA) reached maximum levels by about Day 30 post re
      exposure. Similar results were obtained with cellular enzyme-linked immunosorbent
      assay: 15 days after injection with G. caulleryi spores plus adjuvant, specific
      antibody secretion rate was higher in turbot which had been pre-exposed to G.
      caulleryi spores than in turbot which had not been pre-exposed.

PMID- 9014321
TI  - Immunisation of rainbow trout Oncorhynchus mykiss with a multiple antigen peptide
      system (MAPS).
AB  - To test the effectiveness of a multiple antigen peptide system (MAPS) as a method
      of vaccinating fish against peptides, rainbow trout were immunised with two MAPS
      containing the decapeptide GnRH. The first (MAPS 1) was homologous for GnRH,
      whereas the second (MAPS 2) was heterologous and contained alternating sequences
      of GnRH and a measles virus T cell epitope. Following vaccination with varying
      concentrations of the MAPS, serum antibody titres were monitored for 10 weeks.
      Only MAPS administered in adjuvant elicited an antibody response against GnRH.
      Whilst the kinetics of the responses mirrored those seen in sera from fish
      vaccinated against GnRH coupled to a carrier protein, the magnitude of the
      responses were significantly lower in sera from fish vaccinated with both MAPS.
      Interestingly, higher titres were seen against the MAPS than against GnRH in
      ELISA, possibly reflecting additional epitopes. The data are discussed with
      respect to the need to define T cell epitopes in fish, to allow the synthesis of
      more effective heterologous MAPS for future studies.

PMID- 9014322
TI  - A PCR-RFLP typing method for the caprine Mhc class II DRB gene.
AB  - A polymerase chain reaction (PCR) technique associated with restriction fragment
      length polymorphism (RFLP) analysis has been developed for typing the second exon
      of the caprine Mhc class II DRB gene. By using a maximum of three restriction
      enzymes, corresponding to different combinations of RsaI, BsaI, AccI, NdeII,
      HaeIII and HpaII, this procedure allows to distinguish unequivocally 18 of the 22
      caprine DRB alleles. Forty goats of several breeds were typed with this technique
      and two new RsaI restriction patterns which did not match with previously
      published sequence data were identified. Close associations have been found
      between RFLPs and amino acid substitutions at positions which are expected to be
      involved in the formation of the antigen-recognition site (ARS) of the DR
      molecule. These results suggest that PCR-RFLP may be a useful tool in typing the
      caprine DRB gene and in relating amino acid substitutions at the ARS of the DR
      molecule with disease resistance.

PMID- 9014323
TI  - The precursor protein of the structural apolipoproteins of lipophorin: cDNA and
      deduced amino acid sequence.
AB  - A 10 138 bp cDNA from the fat body of the tobacco hornworm, Manduca sexta, which
      encodes the precursor protein for apolipophorin aPOLP-1 and -II, the structural
      apolipoproteins of the insect lipoprotein, lipophorin, has been cloned and
      sequenced. The cDNA has a single 9915 bp open reading frame beginning at an
      initiating ATG at bp 59 and extending to a stop codon at position 9974. This open
      reading frame encodes a 3305 amino acid protein with a molecular mass of 366 812
      Da. Signal peptide cleavage is predicted to occur after residue 23, leaving a
      3,282 amino acid precursor protein. The precursor protein is arranged with apoLp
      II at the amino terminal end and apoLp-I at the carboxy terminal end. At present,
      the site of cleavage of the precursor protein to generate apoLp-I and -II is
      unknown.

PMID- 9014324
TI  - Transposable elements and gene transformation in non-drosophilid insects.
AB  - This review summarizes recent data on the development of non-drosophilid insect
      transformation systems. The discussion focuses on one particular approach to
      developing transformation systems that relies on the use of short inverted repeat
      type transposable elements analogous to that employed for Drosophila melanogaster
      transformation. Representatives from four families of short inverted repeat-type
      transposable elements have been shown to either act as non-drosophilid gene
      vectors or to have the ability to transpose accurately when introduced into non
      host insect cells. Minos, a member of the Tcl family of elements isolated
      originally from D. hydei has been successfully used as a germline transformation
      vector in the Medfly, Ceratitis capitata. Hermes, a member of the hAT family of
      elements isolated originally from Musca domestica has been successfully used as a
      gene transformation vector in D. melanogaster and has a host range that appears
      to include culicids. hobo, another member of the hAT family of elements isolated
      from D. melanogaster also has a broad host range that includes tephritid
      fruitflies. mariner(Mos), a member of the mariner family of elements isolated
      from D. mauritiana can transpose in calliphorids. Finally, piggyBac/IFP2, a
      member of the TTAA-specific family of elements isolated from Trichoplusia ni can
      transpose when introduced into Spodoptera frugiperda cells. Although routine
      transformation of insects other than D. melanogaster is not possible it is clear
      that the raw materials for the development of efficient transformation systems
      are now available.

PMID- 9014325
TI  - Insect storage proteins: gene families and receptors.
AB  - The accumulation and utilization of storage proteins are prominent events linked
      to the metamorphosis of holometabolous insects. Storage proteins are synthesized
      in fat body, secreted into the larval hemolymph and taken up by fat body shortly
      before pupation. Within the pupal fat body, these proteins are initially stored
      in protein granules, and later proteolytically broken down to supply amino acid
      resources necessary for the completion of adult development. Most, but not all
      storage proteins belong to a superfamily of hexameric larval serum proteins that
      are evolutionarily related to hemocyanin. This article reviews the classification
      of these proteins, based on their amino acid sequences, and the current knowledge
      of the receptors that mediate their selective uptake into pupal fat body.

PMID- 9014326
TI  - Molecular characterization of a cDNA from Pseudaletia unipuncta encoding the
      Manduca sexta allatostatin peptide (Mas-AST).
AB  - A 15-residue neuropeptide, Manduca sexta allatostatin (Mas-AST), strongly
      inhibits juvenile hormone (JH) biosynthesis in vitro by corpora allata (CA) from
      Manduca fifth-stadium larvae and adult females as well as Helicoverpa zea adult
      females (Kramer et al., 1991 Proc. Natl. Acad. Sci (USA) 88, 9458-9462). In
      contrast, this study found that 1.0 microM Mas-AST has no JH biosynthesis
      inhibitory activity in Pseudaletia unipuncta sixth instar larvae or newly-emerged
      (day 0) adults but inhibited CA of 5-day-old adult females by 60%. From a P.
      unipuncta brain cDNA library, was isolated a cDNA that encodes a 125 amino acid
      polypeptide containing the Mas-AST sequence. Within the precursor, Mas-AST is
      situated at the carboxy terminus and is flanked by different dibasic proteolytic
      cleavage signals. The Pseudaletia gene specifying the Mas-AST peptide is present
      as a single copy per haploid genome. Expression of this gene was low in
      Pseudaletia sixth instar larvae, prepupae and early pupae but was relatively high
      in late pupae, and day 1 and 3 adults of both sexes. In day 5 adults, the
      relative transcript level appears to be maintained in females but declines in
      males. This pattern of Mas-AST expression does not correlate well with the
      profile of JH biosynthesis in Pseudaletia, which increases during the first 5
      days of adult life, suggesting additional or alternative functions for this
      peptide.

PMID- 9014327
TI  - The use of decapitated insects to study lipid mobilization in adult Manduca
      sexta: effects of adipokinetic hormone and trehalose on fat body lipase activity.
AB  - In order to perform studies on lipid mobilization in adult M. sexta, it is
      necessary to overcome the effects of starvation and handling, which both provoke
      an increase in hemolymph lipid concentration. When trehalose was injected into
      intact insects, a 35% decrease in the content of the diacylglycerol (DG)-rich
      hemolymph lipoprotein, low density lipophorin (LDLp) was observed within 30 min,
      but the level of LDLp returned to control values after 1 h. Decapitated insects
      exhibited 60% reduction in LDLp concentration and the levels remained low for at
      least 24 h. In contrast to intact insects, injection of trehalose into
      decapitated animals did not alter the LDLp concentration. After decapitation, the
      response to adipokinetic hormone (AKH) and the ability of the fat body to release
      DG into the hemolymph was maintained for at least 24 h. In decapitated insects, 6
      pmol of AKH-stimulated measurable lipid mobilization and a near maximum response
      was obtained with 100 pmol of the hormone. The action of trehalose and AKH on the
      fat body triacylglycerol (TG)-lipase activity in decapitated animals was studied.
      Fat body homogenates from trehalose-treated insects exhibited a TG-lipase
      activity 40% lower than the control insects. Activation of fat body
      triacylglycerol-lipase was observed after injection of AKH, with the extent of
      activation ranging between 97 and 380% ten min after AKH injection. A time course
      study showed that the activation of the fat body triacylglycerol lipase preceded
      the increase in hemolymph LDLp concentration, suggesting that activation of the
      lipase initiates lipid mobilization. It is concluded that decapitated insects
      injected with trehalose is a very useful system for investigating the hormonal
      regulation of lipid mobilization in adult M. sexta.

PMID- 9014328
TI  - Cloning of biogenic amine receptors from moths (Bombyx mori and Heliothis
      virescens).
AB  - Based on the similarity of genes which code for guanine-nucleotide binding
      protein- (G-protein-) coupled receptors, cDNA clones encoding new members of the
      receptor family have been isolated from Bombyx mori and Heliothis virescens. The
      deduced protein structures exhibit highest similarity to tyramine/octopamine and
      serotonin receptors of Drosophila. One of the receptor clones (K50Hel) was
      permanently expressed in the mammalian cell line LLC-PK1. In stimulation
      experiments its responded to octopamine leading to an inhibition of adenylate
      cyclase activity in a dose-dependent manner. Pharmacological studies revealed a
      higher affinity for mianserin than for yohimbine suggesting, that the K50Hel
      clone encoded a neuronal type 3 octopamine receptor. As revealed by in situ
      hybridization, this receptor type is expressed in the central nervous system and
      antennae of moth.

PMID- 9014329
TI  - A comparative analysis of juvenile hormone metabolyzing enzymes in two species of
      Drosophila during development.
AB  - The course of changes in the activities of enzymes degrading juvenile hormone
      (JH), epoxyde hydrolase (JHEH) and JH-esterase (JHE) was studied in two lines of
      Drosophila virilis (101 and 147) and in two lines of D. melanogaster (Canton-S
      and 921283). It was established for D. virilis that changes in the JH titre
      during pupal-adult development is determined by the activity level of JHE rather
      then JHEH, while in D. melanogaster developmental changes in JH titre are related
      to changes in the activity level of both JHE and JHEH. In adults of D. virilis,
      the high level of JH-hydrolysing activity is determined by JHE and in those of D.
      melanogaster by JHEH. Differences in the course of changes in the JHE activity
      level between adults of lines 101 and 147 of D. virilis were found, and also in
      the JHEH activity level between adults of lines Canton S and 921283 of D.
      melanogaster. It was shown that attainment of a definite JHE activity level in
      females of lines 101 and 147 agrees well with the onset of oviposition of
      fertilized eggs. The possible role of JHE in reproduction of D. virilis is
      discussed.

PMID- 9014330
TI  - Coordinated expression and activity of 3-hydroxy-3-methylglutaryl coenzyme A
      synthase and reductase in the fat body of Blattella germanica (L.) during
      vitellogenesis.
AB  - Levels of mRNA for the two 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      synthases, (HMG-S1 and HMG-S2), and for HMG-CoA reductase (HMG-R) of Blattella
      germanica were analyzed in the fat body during the first gonadotrophic cycle. HMG
      S2 and HMG-R showed the highest mRNA levels on day 0 and decreased thereafter,
      whereas HMG-S1, showed faint expression. Western blot using specific antibodies
      for HMG-S1 and HMG-S2 showed no detectable levels for HMG-S1 but a clear pattern
      for HMG-S2. Both results point to a very limited role for HMG-CoA synthase-1 in
      B. germanica fat body that the functional enzyme in this organ is HMG-CoA
      synthase-2. HMG-CoA reductase and synthase proteins shared a cyclic pattern
      (maximum levels at day 4 and minimum levels on days 0 and 8), which was
      coincident with the pattern of activity. The delay between gene transcription and
      protein synthesis suggests a finely regulated translation mechanism. Moreover,
      the pattern of mevalonate synthesis parallels that of vitellogenin production,
      suggesting a coordinate mechanism between the mevalonate pathway and the
      production of vitellogenin.

PMID- 9014331
TI  - Hemocyte surface phenoloxidase (PO) and immune response to lipopolysaccharide
      (LPS) in Ceratitis capitata.
AB  - Bacterial lipopolysaccharide (LPS) attachment at the hemocyte surface is based on
      the crosslinking of surface associated p47 to LPS, via the intermediacy of
      tyrosine derivatives generated by the action of phenoloxidase (PO). This
      attachment is an initial step for LPS internalization from hemocytes
      (Charalambidis et al., 1996). The results presented clearly show the critical
      role of hemocyte associated PO activity in the above processes. Biochemical and
      immunofluorescent analysis demonstrated unambiguously the presence of
      prophenoloxidase (proPO) on the hemocyte surface. The cell-surface expression of
      proPO appeared to be LPS-independent, whereas its activation was LPS-dependent.
      The activation of cell surface proPO involves a limited proteolysis, since upon
      activation with chymotrypsin proPO is converted to a set of smaller molecular
      weight proteins with PO activity. The activation appears to be due to enzyme
      activators, serine proteases, released upon LPS-stimulation. This hypothesis was
      supported from the activation of membrane proPO by the culture medium of
      hemocytes which have been triggered with LPS. In addition, proPO, activation was
      abolished by inhibitors of secretion and PMSF. The release of proPO activators
      upon LPS-stimulation is mediated via protein tyrosine phosphorylation, as
      genistein inhibited proPO activation, a situation similar to that reported by us
      for the release of the effector protein p47 (Charalambidis et al., 1995). The LPS
      stimulated activation of cell-surface proPO is a prerequisite for LPS (either
      cell associated or cell free) internalization, as judged by the resistance of LPS
      binding to dissociation by proteinase K.

PMID- 9014332
TI  - Soluble proteins in chemosensory organs of phasmids.
AB  - Soluble proteins of low molecular weight have been purified from chemosensory
      organs of five species of Phasmids. On the basis of their N-terminal amino acid
      sequences, two classes can be identified. Polypeptides of 14 and 15 kDa,
      expressed in the antennae and legs of Eurycantha calcarata and Extatosoma
      tiaratum, as well as in the antennae of Carausius morosus, bear a close
      similarity (around 45% identity) with a soluble protein associated with the
      sensilla coeloconica of Drosophila melanogaster. Two proteins of 19 and 18 kDa,
      isolated from the antennae and the maxillary palpi, respectively, of Acrophylla
      wuelfingi, are 59 and 75% identical, in their N-terminal region, to a 19 kDa
      antennal protein of Carausius morosus. Similarity between members of the two
      classes is not significant, being limited to two to three identical amino acids
      in the most favorable cases. Finally, a 17 kDa protein, specifically expressed in
      the antennae of Sipyloidea sipylus, did not show any homology with other
      proteins. The expression in sensory organs and the characteristics of these
      proteins may suggest a function in chemosensory transduction.

PMID- 9014333
TI  - Isolation and some molecular properties of a trypsin-like enzyme from larvae of
      European corn borer Ostrinia nubilalis Hubner (Lepidoptera: Pyralidae).
AB  - A one-step high-yielding procedure is presented for the purification of a trypsin
      like proteinase from Ostrinia nubilalis larvae, consisting of benzamidine
      sepharose affinity chromatography. The purified enzyme was homogeneous as judged
      by SDS-PAGE. The enzyme presents a molecular mass of 24 650 Da, a maximum pH
      activity profile of 9.5, a remarkable thermal stability and an optimum
      temperature of about 53 degrees C Km values determined using N alpha-benzoyl-DL
      arginine-ethylester and N alpha-benzoyl-DL-arginine-p-nitro-anilide were 3.2 x
      10(-5) M and 4.1 x 10(-4) M respectively. The proteinase was inhibited by some
      typical serine proteinase inhibitors such as N alpha-tosyl-L-lysine chloromethyl
      ketone, soybean trypsin inhibitors, benzamidine and phenylmethylsulfonyl
      fluoride. In particular, it was competitively inhibited by benzamidine with a Ki
      of 1.2 x 10(-5) M, whereas it was not affected by cysteine proteinases
      inhibitors. Comparative analysis of the amino acid composition and N-terminal
      sequence of O. nubilalis proteinase confirmed that this enzyme is very similar to
      other serine proteinases from lepidopteran larvae.

PMID- 9014334
TI  - Diflubenzuron stimulates phosphorylation of a 39 kDa integumental protein from
      newly molted American cockroach (Periplaneta americana).
AB  - We identified a 39 kilodalton (kDa) protein from newly molted American
      cockroaches (Periplaneta americana), isolated from a 100,000 g precipitate of a
      1000 g supernatant from an integument homogenate, which exhibited increased
      phosphorylation following diflubenzuron (DFB) treatment. This 39 kDa
      phosphoprotein was partially purified from an intracellular membrane vesicle
      containing fractions obtained by discontinuous sucrose density centrifugation.
      Both the interfaces of the 30/40% and 40/50% sucrose density layers were found to
      be enriched in the 39 kDa phosphoprotein. Treatments with various chemicals such
      as the ionophores valinomycin and A23187, the protonophore carbonylcyanide p
      trifluoromethoxy-phenylhydrazone (FCCP), and the vacuolar H(+)-ATPase inhibitor N
      ethylmaleimide (NEM), like DFB, were also found to stimulate phosphorylation of
      39 kDa protein. These results suggest that by disrupting the normal pH gradient
      occurring in certain acidic vacuolar-type membrane vesicles, phosphorylation of
      the 39 kDa protein will be increased. In addition, we found that by decreasing
      the external pH to 5.0 from about neutral, it was possible to stimulate the
      phosphorylation activity of this particular protein, and thus stimulate the
      action of DFB. We concluded the DFB's action is very probably related to its
      ability to disrupt the normal ionic balance of these vacuolar-type vesicles,
      leading to eventual disruption of the proton gradient within the vesicles.

PMID- 9014335
TI  - Salivary thiol oxidase activity of Rhodnius prolixus.
AB  - Cysteine and other thiol compounds can accelerate the unloading of nitric oxide
      (NO) from salivary nitrosyl-nitrophorins of the blood sucking bug Rhodnius
      prolixus. The dependence of NO unloading on cysteine concentration is biphasic,
      showing a maximum between 0.5 and 1 mM cysteine. The proposed mechanism of action
      for the unloading is a series of reactions where cysteine (at low concentrations)
      reacts with the heme group of nitrophorins to form cystine and superoxide. The
      superoxide then reacts with NO to form peroxynitrite, which decays to a mixture
      of nitrite and nitrate anions. At high cysteine concentrations, cysteine is
      converted to cystine and H2O and thus no removal of NO from nitrophorins is
      observed. The thiol oxidase activity of Rhodnius nitrophorins is similar to that
      observed before in plant peroxidases [Pichorner et al., Phytochemistry 31, 3371
      (1992)]. The possible physiological significance of this reaction to probing and
      feeding by R. prolixus is discussed.

PMID- 9014336
TI  - Purification and characterization of five cuticular proteins from the spider
      Araneus diadematus.
AB  - Urea-extractable proteins have been purified from the cephalothoracic cuticle of
      mature Araneus diadematus spiders. Two-dimensional gel electrophoresis showed at
      least 12 major proteins, with pIs between 4.5 and 8.5. Five proteins were
      purified and their primary structure determined, using a combination of mass
      spectrometry and Edman degradation. Based on the amino acid sequence the proteins
      can be divided into two groups, both characterized by hydrophobic regions
      dominated by Ala, Pro and Val. Sequence similarity was observed between all the
      spider cuticle proteins and a number of proteins from other arthropod cuticles.
      Although the similarity seemed to be confined only to a region in the central
      part of the molecules, it does link these very distantly related species.

PMID- 9014337
TI  - Metabolism in vitro of cholesterol and 25-hydroxycholesterol by the larval
      prothoracic glands of Manduca sexta.
AB  - The prothoracic glands in vitro convert 25-hydroxycholesterol (25C) to 25-hydroxy
      7-dehydrocholesterol (7d25C) and to ecdysteroids at a greater rate than
      cholesterol (C) is converted to ecdysteroids via 7-dehydrocholesterol (7dC).
      Mediated via a cytochrome P450 most probably located in the endoplasmic reticulum
      (ER), both intact and extensively homogenized prothoracic glands, as well as
      crude subcellular fractions, were able to 7,8-dehydrogenate 25C to 7d25C eight
      fold more efficiently than they could convert C to 7dC. However, less than a two
      fold difference was observed in the subsequent monooxygenase mediated conversion
      of these two intermediates formed in situ into ecdysteroids, mainly ecdysone (E)
      and 2-deoxyecdysone (2dE) and/or their 3-dehydroderivatives. When 7dC, and
      particularly 7d25C, were made directly available to these tissue preparations,
      their conversion to ecdysteroids greatly exceeded that of the in situ conversion
      of either C or 25C, via 7dC or 7d25C, respectively. Indeed, there was an eight
      fold increase in the VMAX for 25C dehydrogenation by homogenized glands relative
      to the dehydrogenation of C. Most important, however, was the 1000-fold increase
      in the VMAX observed for the direct production of E from emulsified 7d25C by
      gland homogenates relative to E production from 25C via 7d25C synthesized in
      situ. Thus, it is apparent that even after the rapid and efficient conversion of
      25C to 7d25C within the ER, the subsequent rate of conversion of this
      intermediate to E is greatly retarded relative to that observed following the
      direct incubation of emulsified 7d25C with gland homogenates. These differential
      kinetics of direct and indirect 7d25C incorporation into E are interpreted as
      evidence for the existence of a barrier to the efficient translocation of the
      delta 5,7-sterol intermediates from the ER to another site where the subsequent,
      uncharacterized initial conversions leading to ecdysteroids take place. On the
      basis of studies on mammalian adrenal cortical steroidogenesis, this site is
      postulated to be the inner membrane/matrix of the mitochondria. The present data
      support the hypothesis that the translocation of both 7dC and 7d25C, first from
      the site of their probable synthesis within the ER membranes, next through the
      cytosol to the outer mitochondrial membrane, and then across the
      intramitochondrial aqueous space to the inner membrane/matrix compartment, may be
      analogous to the translocation in the adrenal cortex of ER-derived C, first to
      the plasma membrane and/or to the outer mitochondrial membrane and then to the
      inner mitochondrial membrane/matrix for P450scc-mediated conversion into
      pregnenolone.

PMID- 9014338
TI  - Differential incorporation of cholesterol and cholesterol derivatives into
      ecdysteroids by the larval ring glands and adult ovaries of Drosophila
      melanogaster: a putative explanation for the l(3)ecd1 mutation.
AB  - Studies in vitro revealed that intact ring glands of Drosophila melanogaster
      convert tritiated cholesterol (C) and 25-hydroxycholesterol (25C) via 7
      dehydrocholesterol (7dC) and 7-dehydro-25-hydroxycholesterol (7d25C),
      respectively, to ecdysone (E) and 2-deoxyecdysone (2dE), while both intact and
      homogenized ovaries synthesize only 2dE from these precursors. Emulsified 7d25C
      was incorporated directly into ecdysteroids by these tissue preparations at a
      much greater rate than was 7d25C made in situ from 25C. To probe the basis of the
      biochemical defect in the ecdysteroid deficient conditional mutant ecdysoneless
      (ecd1), the differential incorporation into ecdysteroids of C (via 7dC), and
      particularly of 25C (via 7d25C), was measured relative to that observed after the
      incubation of 7d25C directly with both wild type and mutant tissues in vitro at
      30 degrees C, the restrictive temperature. Both C and 25C were equally 7,8
      dehydrogenated in situ to 7dC or 7d25C, respectively, by both wild type and
      mutant tissues at 30 degrees C. However, the rate of subsequent conversion of
      either of these delta 5,7-sterol intermediates synthesized in situ to
      ecdysteroids was reduced an average of 50% in the mutant tissues relative to the
      wild type. Yet, when emulsified 7d25C was incubated directly with either the wild
      type or mutant tissues at the restrictive temperature, the amplified rate of
      conversion of the freely available 7d25C to ecdysteroid by these tissues was
      identical. These data suggest that the defect in ecd1 tissue-mediated
      ecdysteroidogenesis does not involve a "hit" on any of the enzymes involved in
      either the 7,8-dehydrogenation of C or 25C or in the subsequent oxidation of
      7d25C or 7dC to ecdysteroid. Rather, the mutation appears to affect the
      expression of a gene governing the translocation of delta 5,7-sterol
      intermediates from the subcellular compartment where they are synthesized and/or
      stored to the site of subsequent oxidation to ecdysteroid.

PMID- 9014339
TI  - Bmmar1: a basal lineage of the mariner family of transposable elements in the
      silkworm moth, Bombyx mori.
AB  - We describe a transposable element, called Bmmar1, from the genome of the
      silkworm moth, Bombyx mori. This element has features of the Tc1-mariner
      superfamily of transposable elements. Bmmar1 was first detected as a fragment in
      the 5' region of the larval serum protein (BmLSP) gene. Six genomic clones
      characterized each differed from a consensus sequence by 3-5 insertions and
      deletions, as well as an average of 2.3% in nucleotide sequence. The genome
      contains approximately 2400 copies of Bmmar1. Maximum parsimony phylogenetic
      analysis of the relationship of Bmmar1 and other members of the Tc1-mariner
      superfamily, based on their encoded transposase amino acid sequences, indicates
      that it represents a basal lineage of the mariner family. In particular Bmmar1
      encodes a D,D37D motif thought to be the catalytic domain of mariner
      transposases. Bmmar1 considerably increases the known diversity of this
      widespread family of transposons. A new naming system is proposed for members of
      the family.

PMID- 9014340
TI  - Localization of the Drosophila male accessory gland protein Acp36DE in the mated
      female suggests a role in sperm storage.
AB  - In many insect species, sperm transferred in a single mating are stored by the
      female in specialized organs and are gradually used to fertilize eggs. Thus,
      insects must have mechanisms to ensure that substantial numbers of sperm reach
      and become stored in the storage organs. We report here that a glycoprotein,
      Acp36DE, made by the accessory glands of Drosophila melanogaster males, shows
      localization in the mated female suggesting a role in sperm storage. In the mated
      female, Acp36DE associates with the wall of the oviduct, just anterior to the
      openings of the sperm storage organs. Acp36DE also associates with the leading
      edge of the sperm mass. It does not enter the hemolymph. Complete localization of
      Acp36DE in the mated female requires sperm and the presence of eggs in the
      ovaries. We hypothesize that Acp36DE, or a complex containing it, forms a barrier
      that "corrals" sperm near the openings to the sperm storage organs. Concentration
      of sperm here could facilitate their efficient storage. Acp36DE remains in the
      genital tract for several hours after mating, concurrent with the time that sperm
      are being stored. Facilitation of sperm storage by Acp36DE may also explain the
      previously observed effect of this protein on sperm competition.

PMID- 9014341
TI  - Studies on the interaction between cytochrome c and cis-PtCl2(NH3)2.
AB  - The interactions between cytochrome c and cis-PtCl2(NH3)2 under different
      conditions are reported. It is found that cis-PtCl2(NH3)2 is highly selective to
      bind to sulfur-containing Met residue and the interaction mode of cis-PtCl2(NH3)2
      with cytochrome c is different from that of PtCl4(2-) with cytochrome c. The
      binding sites of platinum complex in the protein were characterized by analysis
      of the molar ratio of two metal atoms (Pt and Fe), 1H NMR spectra, UV-vis
      spectra, and differential pulse voltammetry.

PMID- 9014342
TI  - Synthesis and characterization in solid and solution of trans-dichloro-1-(2', 6'
      difluorophenyl)-1H,3H-thiazolo [3,4-a]-benzimidazole(tri-n-propyl-phosphine)
      palladium(II)": a palladium(II) complex of a ligand with anti-HIV properties.
AB  - The 1-(2',6'-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (L), a highly
      potent nonnucleoside HIV-1 reverse transcriptase inhibitor, has been reacted with
      [Pd2Cl4(PPr3n)2] in order to study its coordinating properties towards metal
      ions. The structure of the synthesized product has been examined in solution by
      1H and 13C NMR, and in solid by X-ray analysis. [Pd(PPr3n)(L)Cl2] has a trans
      structure and L coordinates through imine nitrogen. The loss of anti-HIV
      properties of L, by complexation, suggests that, unless biological inactivation
      is simple due to steric reasons, the imine nitrogen atom is an active site of the
      molecule.

PMID- 9014343
TI  - Aluminum (III) induces alterations on the physical state of the erythrocytic
      membrane: an ESR evaluation.
AB  - The action of aluminum [Al(III)] as Al(acac)3 on erythrocytes causes biophysical
      effects such as osmotic fragility and echino-acanthocytes formation. In this
      paper, we present these effects in terms of variation of membrane fluidity,
      together with findings regarding conformational modifications of membrane
      proteins consequent to Al(III) exposure, as well as the effects on the mobility
      of the membrane protein bound sialic acid. To this end, we utilized ESR
      measurements of rabbits and humans erythrocytic ghosts after probing or labeling
      with suitable stable radicals used as spin probes or labels. Our results show
      that the lipophilic, hydrolytically stable toxicant Al(acac)3 causes a remarkable
      reduction of membrane fluidity in rabbit erythrocytes, an appreciable structural
      compacting effect on cytoskeletal and transmembrane proteins, as well as a
      reduction of rotational mobility of cell-surface sialic acid of human
      erythrocytes.

PMID- 9014344
TI  - The interaction of mixed-ligand square-planar complexes with calf thymus DNA.
AB  - The interactions among the complexes [M(bpy)(en)]-(ClO4)2, [M(biq)(en)](ClO4)2(M
      = Pt or Pd; bpy = 2,2'-bipyridine, biq = 2,2'-biquinoline and en =
      ethylenediamine), [Pd(4,4'R2bpy)(en)] (ClO4)2(R = CH3 or C6H5), and [Pd(bpy)(R,
      R' N(CH2)2NR",R"')] (ClO4)2(R = R' = R" = R'" = H; R = CH3, R' = R" = R"' = H; ;
      R = CH3, R' = H, R" = CH3, R'" = H; R= C2H5, R' = R" = R"' = H; ; R = C2H5, R' =
      H, R" = C2H5, R'" = H) and calf thymus DNA have been studied via absorption and
      denaturation experiments. The processes give rise to: i) large bathochromic
      shifts and substantial hypochromicity of the absorption bands of the complexes,
      and ii) an increase in the DNA melting temperature larger than that observed for
      the known intercalator, ethidium bromide. Binding constants, K, have been
      determined spectrophotometrically at 25 degrees C, pH 7, and various ionic
      strengths, using the McGhee-von Hippel approach. Plots of log K vs. log [Na+] are
      linear, but the magnitudes of the slopes are always lower than expected on the
      basis of the formal +2 charge of the complexes. K values are larger for those
      substrates containing a greater number of aromatic rings; the presence of methyl
      substituents in the substances does not alter the binding avidity if substitution
      is at NH2 groups of ethylenediamine, while the binding strength is enhanced when
      substitution is at bpy rings. Homologous palladium (II) and platinum (II)
      complexes show very similar interaction patterns with DNA.

PMID- 9014345
TI  - Synthesis, antitumor activity and acute toxicity of diammine/diamino-cyclohexane
      platinum(II) complexes with oxygen-ligating leaving group.
AB  - In order to clarify the relation between the reactivity of the leaving groups in
      cisplatin-like complexes and their activity / toxicity, six new complexes of the
      formula Pt(NH3)2X and Pt(dach)X (where X is selenato, anion of squaric acid, or
      demethylcantharic acid) have been synthesized and compared. These complexes have
      been characterized by elemental analysis, infrared spectroscopy, and conductivity
      measurements. Six human neoplastic cell lines (HCT, KB, BGC, HL-60, K-563 and Bel
      7402) were used to screen these compounds. The results demonstrated that four of
      them have comparable IC50 and even lower IC50 in a few kinds of tumor cell lines
      compared to cisplatin. Their LD50 values showed that the toxicity of these
      platinum complexes is related to the reactivity of the leaving groups. All of
      these complexes have lower acute toxicity than cisplatin, but the anticancer
      activity is not affected.

PMID- 9014346
TI  - Alkaloid 223A: the first trisubstituted indolizidine from dendrobatid frogs.
AB  - The structure of alkaloid 223A (1), the first member of a new class of amphibian
      alkaloids, purified by HPLC from a skin extract of a Panamanian population of the
      frog Dendrobates pumilio Schmidt (Dendrobatidae) has been established as
      (5R,6S,8R,9S)- or (5S,6R,8S,9R)-6,8-diethyl-5-propylindolizidine, based on GC-MS,
      GC-FTIR, and 1H-NMR spectral studies. Three higher homologs of 223A, namely
      alkaloids 237L (2), 251M (3), and 267J (4), have been detected in other extracts,
      and tentative structures are proposed.

PMID- 9014347
TI  - Cochliobolic acid, a novel metabolite produced by Cochliobolus lunatus, inhibits
      binding of TGF-alpha to the EGF receptor in a SPA assay.
AB  - Cochliobolic acid (1), a novel biologically active natural product, is produced
      by submerged fermentation of Cochliobolus lunatus. Compound 1 was determined to
      be a novel polyketide possessing a substituted tetrahydrofuran ring, a conjugated
      polyene chain and a 1,2-diketone moiety, by interpretation of NMR, MS, and UV/vis
      spectroscopic data. Compound 1 inhibits the binding of TGF-alpha to the EGF
      receptor of the human epidermal cell line A431 in a SPA assay with an IC50 of 1.6
      microM.

PMID- 9014348
TI  - Haliclostanone sulfate and halistanol sulfate from an Indo-Pacific Haliclona
      sponge.
AB  - Two steroids, haliclostanone sulfate (1) and halistanol sulfate (3), were
      isolated from a Haliclona sp. marine sponge. The structure of the new compound 1
      was established based on its spectroscopic data and the properties of a
      pentaacetate derivative 2. Compound 1 is unique in that it possesses the rare cis
      C/D ring junction precedented only in marine sterols, contignasterol (4) and
      xestobergsterols A (5), B (6), and C (7).

PMID- 9014349
TI  - Oxysporidinone: a novel, antifungal N-methyl-4-hydroxy-2-pyridone from Fusarium
      oxysporum.
AB  - Oxysporidinone (1), a novel 3,5-disubstituted N-methyl-4-hydroxy-2-pyridone, was
      isolated from fermentations of Fusarium oxysporum (CBS 330.95) by counter-current
      chromatography. The structure was determined by spectroscopic methods including
      NMR, MS, IR, and UV analysis. Oxysporidinone exhibited growth inhibitory activity
      against several common plant pathogenic fungi.

PMID- 9014350
TI  - Bioactive compounds from Taiwania cryptomerioides.
AB  - Two new sesquiterpenes, 10 alpha-hydroxyamorphan-4-en-3-one (1) and 4 alpha
      methylcadinane-4 alpha-methyl-1 alpha,2 alpha,10 alpha-triol (2), together with
      four known compounds, sesquiterpenes 10 alpha-hydroxycadinan-4-en-3-one (3) and
      alpha-cadinol (4), diterpene ferruginol and lignan helioxanthin, were isolated
      from the whole plant of Taiwania cryptomerioides under bioassay-guided
      fractionations. The structures of 1 and 2 were elucidated mainly by the NMR
      spectroscopic analyses. Bioactivities of the isolated compounds against brine
      shrimp, yellow fever mosquito larvae, and human tumor cells are reported;
      compound 4 was the most bioactive, showing selectivity for the human colon tumor
      cell line (HT-29).

PMID- 9014351
TI  - Luffasterols A-C, 9,11-secosterols from the Palauan sponge Luffariella sp.
AB  - The Palauan sponge Luffariella sp. contained manoalide (6) and secomanoalide (7)
      as the major metabolites. The minor metabolites, luffasterols A-C (3-5) are 9,11
      secosterols that contain a 3 beta-acetoxy-5 alpha,6 alpha-epoxy-9-oxo-9,11
      secocholest-7-en-11-al ring system joined to three different side chains. The
      structures of the luffasterols were elucidated by interpretation of spectroscopic
      data.

PMID- 9014352
TI  - Metabolism studies of indole derivatives using a staurosporine producer,
      Streptomyces staurosporeus.
AB  - From a tryptophan metabolic study, 3-(hydroxyacetyl)indole, indole-3
      carboxaldehyde, and o-aminobenzoic acid were obtained as tryptophan metabolites
      from a staurosporine (1) producer, Streptomyces staurosporeus. A new tryptamine
      metabolite, (3aR,8aS)-1-acetyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3- b]indol-3a-ol
      (2), was isolated along with Nb-acetyltryptamine using S. staurosporeus fed with
      tryptamine. The unusual compound 2 was proposed as a further metabolite of Nb
      acetyltryptamine through an enzymatic oxidative cyclization. Examination of the
      metabolites from the feeding of 5- and 6-fluorotryptamines using the same
      microorganism afforded the two novel compounds 3 and 4 as the 5- and 6-fluoro
      derivatives of 2. However, 5-hydroxytryptamine failed to generate the 5-hydroxy
      derivative of 2. Indole-ring-substituted metabolites of staurosporine (1) were
      not observed.

PMID- 9014353
TI  - Natural products in drug discovery and development.

PMID- 9014354
TI  - Shape of stars and optical quality of the human eye.
AB  - Star images are entoptic phenomena that most people can perceive when looking at
      bright point sources in darkness. Diffraction and/or ocular aberrations seem to
      be a plausible cause for the star patterns, but to our knowledge no objective
      recordings of retinal optical images showing these characteristic patterns have
      been reported before. We have projected a small Gaussian spot of light onto the
      retina and registered the aerial image formed externally through a fully dilated
      pupil [one-and-a-half-pass method [J. Opt. Soc. Am. A 12, 2385 (1995)]]. We have
      verified that, for fully dilated pupils (> 9 mm), the blur caused by the finite
      size of the Gaussian spot is small. Consequently, these aerial images are a
      reasonably good approximation of the (inverted) optical point-spread function of
      the eye. These objectively recorded images displayed the distinctive radiating
      patterns of star images, which were compared with subjective patterns sketched
      out by the same observers. A strikingly close match was found between the
      objective and the subjective patterns of the same eyes. In addition, we computed
      the diffraction patterns produced by a simple schematic model of the suture lines
      of the anterior lens surface, also obtaining star-shaped images. These results
      support the commonly accepted hypothesis of a purely optical origin of subjective
      star images.

PMID- 9014355
TI  - Discrimination of the spatial derivatives of horizontal binocular disparity.
AB  - Observers discriminated the relative disparity, disparity gradient, and disparity
      curvature of surfaces defined by horizontal binocular disparity in random-dot
      stereograms. In experiment 1, thresholds for discriminating the depth of
      sinusoidal corrugations were very similar for different corrugation frequencies,
      despite large differences in disparity gradient and disparity curvature. Thus
      observers used a relative disparity cue in preference to a slant or curvature
      cue. Experiment 2 isolated the spatial derivatives of disparity by jittering the
      other available cues, using surfaces with square-wave, triangle-wave, and
      parabolic-wave profiles. Weber fractions were 4%-10% for relative disparity, 6%
      12% for disparity gradient, and 15%-30% for disparity curvature. Experiment 3
      confirmed this result for larger surfaces. The study supports the view that human
      stereoscopic vision aims to represent the local scene relative to the observer,
      at the expense of computing intrinsic properties of objects, such as curvature.

PMID- 9014356
TI  - Spectral mechanisms of spatially induced blackness: data and quantitative model.
AB  - Spectral efficiency functions and tests of additivity were obtained with three
      observers to identify possible chromatic contributions to spatially induced
      blackness. Stimuli consisted of a series of monochromatic (400-700 nm; 10-nm
      steps), 52-arcmin circular test lights surrounded by broadband (x = 0.31, y =
      0.37), 63-138-arcmin annuli of fixed retinal illuminance. The stimuli were imaged
      on the fovea in Maxwellian view as 500-ms flashes with 10-s interstimulus
      intervals. Observers decreased the intensity of the test center until it was
      first perceived as completely black. Action spectra determined for two surround
      levels [2.5 and 3.5 log trolands] had three sensitivity peaks (at approximately
      440, 540, and 600 nm), However, when monochromatic surrounds were adjusted to
      induce blackness in a broadband center, action spectra were unimodal and
      identical to functions obtained by heterochromatic flicker photometry. Tests of
      additivity revealed that when blackness is induced by broadband surround into a
      bichromatic center, there is an additivity failure of the cancellation type. This
      additivity failure indicates that blackness induction is influenced, in part, by
      signals from opponent-chromatic pathways. A quantitative model is presented to
      account for these data. This model assumes that blackness induction is determined
      by the ratio of responses to the stimulus center and the annulus, and while
      signals form the annulus are based only on achromatic information, responses from
      the center are based on both chromatic and achromatic properties of the stimulus.

PMID- 9014357
TI  - Radiative transfer implies a modified reciprocity relation.
AB  - The usual reciprocity relations of radiative transfer do not hold two points
      located in regions of different index of refraction. Modified reciprocity
      relations that involve the relative index are derived. The result has
      computational as well as theoretical consequences.

PMID- 9014358
TI  - Workplace performance studies of half-mask respirators.

PMID- 9014359
TI  - Fit testing under the new 42 CFR Part 84.

PMID- 9014360
TI  - Limiting diisocyanate exposure.

PMID- 9014362
TI  - A chlorate-resistant mutant defective in the regulation of nitrate reductase gene
      expression in Arabidopsis defines a new HY locus.
AB  - Light acts both directly as a signal and indirectly through photosynthesis to
      regulate the expression of genes encoding nitrate reductase (NR). Here, we report
      the isolation and characterization of a novel chlorate-resistant mutant that is
      defective in the regulation of NR gene expression. The response of NR2, but not
      NR1 or the gene encoding nitrate reductase (NiR), to light signals was impaired
      in this Arabidopsis mutant, designated cr88. In addition to NR2, the light
      regulation of the genes encoding the chlorophyll a/b binding protein (CAB) and
      the small subunit of ribulose bisphosphate carboxylase (RBCS) was also impaired
      in this mutant. These results suggest that the pathway through which light
      regulates the expression of NR2, CAB, and RBCS genes is different from those that
      regulate the expression of NR1 and NiR. An examination of the deetiolation
      process under different light spectrum showed that cr88 is defective in red light
      mediated deetiolation. Complementation tests with various long hypocotyl (hy)
      mutants indicated that CR88 identifies a new HY locus. The possible functions of
      CR88 are discussed.

PMID- 9014361
TI  - Hexokinase as a sugar sensor in higher plants.
AB  - The mechanisms by which higher plants recognize and respond to sugars are largely
      unknown. Here, we present evidence that the first enzyme in the hexose
      assimilation pathway, hexokinase (HXK), acts as a sensor for plant sugar
      responses. Transgenic Arabidopsis plants expressing antisense hexokinase (AtHXK)
      genes are sugar hyposensitive, whereas plants overexpressing AtHXK are sugar
      hypersensitive. The transgenic plants exhibited a wide spectrum of altered sugar
      responses in seedling development and in gene activation and repression.
      Furthermore, overexpressing the yeast sugar sensor YHXK2 caused a dominant
      negative effect by elevating HXK catalytic activity but reducing sugar
      sensitivity in transgenic plants. The result suggests that HXK is a dual-function
      enzyme with a distinct regulatory function not interchangeable between plants and
      yeast.

PMID- 9014363
TI  - Photo and hormonal control of meristem identity in the Arabidopsis flower mutants
      apetala2 and apetala1.
AB  - We have analyzed the contributions of phytochrome and gibberellin signal
      transduction to the control of flower meristem identity in the Arabidopsis
      mutants apetala1 (ap1) and apetala2 (ap2). ap1 flowers are partially defective
      for the establishment of flower meristem identity and are characterized by the
      production of ectopic secondary or axillary flowers and by branching. Axillary
      flower production is also induced in ap2-1 flowers by short-day photoperiod and
      is suppressed by hy1, a mutation blocking phytochrome activity. The production of
      axillary flower by ap2-1 is also suppressed by exogenous gibberellins and by
      spindly (spy), a mutation that activates basal gibberellin signal transduction in
      hormone-independent manner. Ectopic axillary flower production and floral
      branching by ap1 flowers are also suppressed by spy. We conclude that
      gibberellins promote flower meristem identity and that the inflorescence-like
      traits of ap2-1 and ap1-1 flowers are due in part to SPY gene activity.

PMID- 9014364
TI  - Rapid induction by wounding and bacterial infection of an S gene family receptor
      like kinase gene in Brassica oleracea.
AB  - A receptor-like kinase, SRK, has been implicated in the autoincompatible response
      that leads to the rejection of self-pollen in Brassica plants. SRK is encoded by
      one member of a multigene family, which includes several receptor-like kinase
      genes with patterns of expression very different from that of SRK but of unknown
      function. Here, we report the characterization of a novel member of the Brassica
      S gene family, SFR2. RNA gel blot analysis demonstrated that SFR2 mRNA
      accumulated rapidly in response both to wounding and to infiltration with either
      of two bacteria: Xanthomonas campestris, a pathogen, and Escherichia coli, a
      saprophyte. SFR2 mRNA also accumulated rapidly after treatment with salicylic
      acid, a molecule that has been implicated in plant defense response signaling
      pathways. A SFR2 promoter and reporter gene fusion was introduced into tobacco
      and was shown to be induced by bacteria of another genus, Ralstonia (Pseudomonas)
      solanacearum. The accumulation of SFR2 mRNA in response to wounding and pathogen
      invasion is typical of a gene involved in the defense responses of the plant. The
      rapidity of SFR2 mRNA accumulation is consistent with SFR2 playing a role in the
      signal transduction pathway that leads to induction of plant defense proteins,
      such as pathogenesis-related proteins or enzymes of phenylpropanoid metabolism.

PMID- 9014365
TI  - Alleles of Pto and Fen occur in bacterial speck-susceptible and fenthion
      insensitive tomato cultivars and encode active protein kinases.
AB  - The Pto gene was derived originally from the wild tomato species Lycopersicon
      pimpinellifolium and confers resistance to Pseudomonas syringae pv tomato strains
      expressing the avirulence gene avrPto. The Fen gene is also derived from L.
      pimpinellifolium and confers sensitivity to the insecticide fenthion. We have now
      isolated and characterized the alleles of Pto and Fen from cultivated tomato, L.
      esculentum, and designated them pto and fen. High conservation of genome
      organization between the two tomato species allowed us to identify the pto and
      fen alleles from among the cluster of closely related Pto gene family members.
      The pto and fen alleles are transcribed and have uninterrupted open reading
      frames that code for predicted proteins that are 87 and 98% identical to the Pto
      and Fen protein kinases, respectively. In vitro autophosphorylation assays
      revealed that both the pto and fen alleles encode active kinases. In addition,
      the pto kinase phosphorylates a previously characterized substrate of Pto, the
      Pto-interacting Pti1 serine/threonine kinase. However, the pto kinase shows
      impaired interaction with Pti1 and with several previously isolated Pto
      interacting proteins in the yeast two-hybrid system. The observation that pto and
      fen are active kinases and yet do not confer bacterial speck resistance or
      fenthion sensitivity suggests that the amino acid substitutions distinguishing
      them from Pto and Fen may interfere with recognition of the corresponding signal
      molecule or with protein-protein interactions involved in the Pto- and Fen
      mediated signal transduction pathways.

PMID- 9014367
TI  - Phosphorylation of Opaque2 changes diurnally and impacts its DNA binding
      activity.
AB  - In the maize endosperm, the Opaque2 (O2) basic leucine zipper transcriptional
      activator regulates the expression of a subset of the zein seed storage protein
      gene family. Immunodetection of wild-type or mutant O2 polypeptides fractionated
      by SDS-PAGE resolved a closely spaced doublet migrating in the 68- to 72-kD
      range, whereas by using isoelectric focusing, seven to nine isoforms were
      detected for each allele. Phosphatase treatment simplified the protein patterns
      to a single band corresponding to the nonphosphorylated component. In vivo and in
      vitro labeling confirmed that O2 can be phosphorylated. In protein gel blots
      probed with DNA, only the nonphosphorylated and hypophosphorylated O2
      polypeptides were able to bind an oligonucleotide containing the O2 binding
      sequence. Upon in situ dephosphorylation of the focused isoforms by phosphatase
      treatment of the isoelectric focusing filter, the hyperphosphorylated forms
      acquired DNA binding activity. The ratio among the various isoforms remained
      constant throughout the developmental stages of endosperm growth but changed from
      daytime to nighttime, with a significant increase of the hyperphosphorylated
      forms during the night period. These results indicate that O2 exists in vivo as a
      pool of differently phosphorylated polypeptides and demonstrate that O2 DNA
      binding activity is modulated by a phosphorylation/dephosphorylation mechanism
      that appears to be influenced by environmental conditions.

PMID- 9014368
TI  - A trypsin inhibitor from snail medic seeds active against pest proteases.
AB  - A protein trypsin inhibitor from seeds of snail medic (Medicago scutellata),
      MsTI, has been purified by ion-exchange chromatography, gel-filtration
      chromatography and reverse-phase HPLC. The protein inhibits the catalytic
      activity of bovine beta-trypsin, with an apparent Kd of 1.8 x 10(-9), but
      exhibits no activity towards bovine alpha-chymotrypsin. Moreover, MsTI inhibits
      the trypsin-like proteinase activity present in larvae of the crop pests
      Adoxophyes orana, Hyphantria cunea, Lobesia botrana and Ostrinia nubilalis. The
      complete amino acid sequence of MsTI consists of 62 residues corresponding to a
      M(r) of 6925. Sequence comparison shows that MsTI exhibits significant similarity
      to other proteins belonging to the Bowman-Birk trypsin inhibitor family, and the
      closest identity (81%) with the wound-induced trypsin inhibitor from Medicago
      sativa leaves.

PMID- 9014369
TI  - Chemical basis of the resistance of barley seeds to pathogenic fungi.
AB  - The 5-(n)-alkylresorcinol fraction of the epicuticular waxes of Hordeum vulgare
      seeds appeared to be responsible for their in-born resistance to pathogenic fungi
      such as Aspergillus niger and Penicillium crysogenum. The antifungal properties
      of this fraction were evaluated qualitatively and quantitatively with a novel
      bioassay where the extreme lipophilicity of these compounds was taken into
      account. The minimum inhibitory concentration in the fungi tested ranged from 5.6
      to 10 micrograms cm-2 for the alkyresorcinols. The behaviour of the different
      cultivars against these fungi could be predicted by measuring the natural amount
      of resorcinols of each variety by TLC-scanning densitometry. The ranking of
      cultivars thus established correlated well with the field behaviour of each
      cultivar, providing a useful and rapid method for predicting the behaviour
      against fungi of new varieties being developed.

PMID- 9014370
TI  - Plant polyphenols: biologically active compounds or non-selective binders to
      protein?
AB  - Twenty phenolic compounds, representatives of proanthocyanidins and gallic
      acid/hexahydroxyldiphenic acid esters of glucose, have been assessed for their
      ability to inhibit binding of specific radioligands to 16 receptors. The
      receptors utilized were alpha 1-, alpha 2- and beta-adrenoceptors, adenosine 1,
      dopamine 1 and 2, muscarinic, Ca2+ channel, sulphonylureas, 5HT1, 5HT1A, 5HT2,
      histamine 1, benzodiazepine, opiate and Na+/K/ATPase. These phenolic compounds
      failed to inhibit ligands binding to 10 of the receptors under the test
      conditions. The most susceptible receptors to phenolic binding were beta
      adrenergic, 5HT1 and opiate. Some of the compounds tested showed selectivity for
      a single or for two receptors. The inhibition of binding of radioligands to
      receptors by the phenolic compounds cannot be explained solely in terms of
      phenolic-protein binding. The results indicate that the removal of tannins from
      plant extracts prior to screening for receptor activities may result in missing
      biologically active compounds with specificity of action.

PMID- 9014371
TI  - Triterpenoid saponins from the roots of Zygophyllum species.
AB  - Two new triterpenoid saponins, 3-O-[beta-D-2-O-sulphonylglucopyranosyl]-quinovic
      acid-28-O-[beta-D-glucopyranosyl] ester (zygophyloside G), 3-O-[alpha-L
      arabinopyranosyl-(1-->2)-beta-D-quinovopyranosyl++ +]-quinovic acid-28-28-O-[beta
      D-glucopyranosyl] ester (zygophyloside H), and seven known saponins have been
      isolated. The structures were established primarily on the basis of NMR
      spectroscopy. The assignment of all NMR signals was performed by means of 1H-1H
      COSY-45, NOESY, TOCSY, 13C APT, HMQC and HMBC experiments. The determination of
      the glycosylation sites was possible by the HMBC experiments.

PMID- 9014372
TI  - A triterpenoid saponin from Maesa ramentacea.
AB  - The structure of a piscicidal triterpenoid saponin (saponin A) isolated from the
      leaves of Maesa ramentacea has been shown to be 3-O-[[(alpha-rhamnopyranosyl (1-
      >2)-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl (1-->3)]-[beta-D
      glucopyranosyl(1-->2)]-beta-D-glucuronopyranosyl] barringtogenol C21, 22-O
      diangeloate. Extensive use was made of homo- and heteronuclear 2D NMR techniques.

PMID- 9014373
TI  - Leonticins D-H, five triterpene saponins from Leontice kiangnanensis.
AB  - Five new triterpene saponins, leonticins D-H, were isolated from the tubers of
      Leontice kiangnanensis. Based on a combination of chemical degradation and
      spectroscopic analysis (negative ion FAB mass spectrometry and 2D NMR
      experiments), their structures were characterized as 3-O-alpha-L-arabinopyranosyl
      caulophyllogenin 28 -O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-
      >6-beta-D- glucopyranoside, 3-O-[beta-D-glucopyranosyl -(1-->3)]-[beta-D
      glucopyranosyl- (1-->2)]-alpha-L-arabinopyranosyl-oleanolic acid 28-O-alpha-L
      rhamnopyranosyl- (1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside, 3
      O-[beta-D-glucopyranosyl-(1-->3)]-[beta-D-glucopyranosyl-(1-->2)]-alph a-L 
      arabinopyranosyl-hederagenin 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-
      glucopyranosyl-(1-->6)-beta-D-glucopyranoside, 3-O-beta-D-xylopyranosyl- (1-->3)
      beta-D-galactopyranosyl-(1-->4)-beta-D- glucopyranosyl-(-->3)-alpha-L
      arabinopyranosyl-echinocystic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-
      glucopyranosyl-(1-->6)-beta-D-glucopyranoside, respectively.

PMID- 9014374
TI  - Saponins from Oxytropis bicolor.
AB  - Two new trace saponins were isolated from Oxytropis bicolor by column
      chromatography and preparative TLC on silica gel. The structures were elucidated
      as 16-O--[beta-D-glucopyranosyl(1-->3)-beta-D-glucopyranosyl]-(20S, 24S)-3 beta,
      16 beta, 20,24,25-pentahydroxy-9,19-cyclolanostane and 16-O-[beta-D
      glucopyranosyl(1-->3)-beta-D-glucopyranosyl-20-O-alpha-L -arabinopyranosyl
      (20S,24X)-3 beta, 16 beta,20,25-pentahydroxy-9, 19-cyclolanostane on the basis of
      chemical evidence and spectral analysis.

PMID- 9014375
TI  - Four flavonoid glycosides from Peganum harmala.
AB  - The aerial parts of Peganum harmala yielded four new flavonoids: acacetin 7-O
      rhamnoside, 7-O-[6"-O-glucosyl-2"-O-(3'''-acetylrhamnosyl)glucoside and 7-O-(2'''
      O-rhamnosyl-2"-O-glucosylglucoside), and the glycoflavone 2'''-O-rhamnosyl-2"-O
      glucosylcytisoside.

PMID- 9014376
TI  - Every action causes a reaction: the inevitable backlash against managed care.

PMID- 9014377
TI  - Reperfusion for acute myocardial infarction: 1997 and beyond.

PMID- 9014378
TI  - The constitutionality of physician-assisted suicide: the cases and issues before
      the US Supreme Court.

PMID- 9014379
TI  - The Bypass Angioplasty Revascularization Investigation (BARI) trial: implications
      for clinical practice.

PMID- 9014380
TI  - Nonresolving alveolar infiltrates in a 43-year-old woman.

PMID- 9014381
TI  - When and how to use serum tumor markers in clinical practice.

PMID- 9014382
TI  - Cardioversion or rate control for atrial fibrillation: balancing risks and
      benefits.

PMID- 9014383
TI  - Extraesophageal presentations of gastroesophageal reflux disease: the case for
      aggressive diagnosis and treatment.
AB  - Gastroesophageal reflux disease (GERD) has a number of extraesophageal
      presentations, including noncardiac chest pain, asthma, and laryngitis. Although
      24-hour esophageal pH monitoring is the best test to diagnose GERD, an empiric
      approach to treatment, using an aggressive acid suppression regimen such as a
      proton-pump inhibitor, may be more cost-effective.

PMID- 9014384
TI  - Experiences of a sleep disorders center: 1700 patients later.
AB  - Sleep studies reveal many patients to have specific sleep abnormalities different
      from what might be suspected from the clinical history. For example, in our
      experience, patients who were later found to have central sleep apnea presented
      with chief complaints of excessive sleepiness or insomnia. In patients requesting
      evaluation for sleep apnea, screening studies that detect only sleep-disturbed
      breathing (ie, oximetry) may miss other diagnoses in one fourth of cases.

PMID- 9014385
TI  - Cluster headache.

PMID- 9014386
TI  - RNdex case management offers Internet access.

PMID- 9014387
TI  - A viable alternative to desktop PCS?

PMID- 9014388
TI  - Redefining continuing education delivery.
AB  - Just as technology is transforming the delivery of education, the Internet and
      advanced telecommunication applications are changing the "face" of CE and the
      connotation of "lifelong learning." As late as the mid-1980s, a discussion of
      computer applications in nursing CE focused on the "timely" transition to
      microcomputers as tools for the enhancement of managerial tasks for increased
      productivity. Even as recently as 1990, there seemed to be "time" for those
      providers who were "slower to adopt innovation" to "catch up." Now, the CE
      provider who does not integrate the microcomputer and advanced telecommunications
      as an integral component of their delivery modalities may be outsourced rapidly
      by an educational or commercial competitive unit that is able to utilize the
      communication medium, mergers and partnerships, enterprise, and individual
      lifestyle and learning patterns that will epitomize the CE unit of the 21st
      century. As with the "re-engineering" of nursing education, the "re-engineered"
      delivery modalities of evolving CE entity might now best be conceptualized on a
      continuum from the traditional mode that time and place dependent to a mode of
      synchronous and asynchronous data and advanced telecommunication. Delivery
      methods will need to be selected according to the target populations, content,
      and situation. The health-care educational provider may discover, as in other
      industries, that a combination of distance and residential offerings will be the
      most successful medium for the delivery of CE to the progressively more
      "information and technologically savvy" lifelong learner of the 21st century. In
      addressing the dramatic effects of the information technology era on the
      refocused multimedia/interactive delivery method for student education, educators
      amply quoted Bob Dylan's phrase of the 1960s, "The times, they are a-changing."
      And so, we see that the times are also changing at an astronomical rate for the
      health-care educational provider as well as the individual health-care worker
      consumer. A number of national and world-wide trends are propelling rapid changes
      in the delivery modalities and types of emerging providers for health-care CE.
      Examples of these advanced telecommunications applications of CE opportunities
      for health-care personnel are becoming more prevalent in the literature and the
      pattern of CE marketing, and delivery evolution can be seen readily on the
      Internet. Continued program success and viability will belong to the individuals
      and organizations who are able to conceptualize and envision the positive
      transformations and opportunities that can occur from the evolving paradigm of
      education for the lifelong learner of the 21st century.

PMID- 9014389
TI  - The development of a computerized clinical placement tracking application in
      nursing education.

PMID- 9014390
TI  - Nursing Interventions Classification implementation issues in five test sites.
AB  - The authors describe the implementation of the Nursing Interventions
      Classification (NIC), a standardized nursing language in five test sites:
      Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Genesis Medical
      Center, Davenport, Iowa; Loyola University Medical Center, Maywood, Illinois;
      Oaknoll Retirement Residence, Iowa City, Iowa; and The University of Iowa
      Hospitals and Clinics, Iowa City, Iowa. A description of NIC is provided along
      with a discussion of implementation issues and recommendations for
      implementation.

PMID- 9014391
TI  - Contract negotiation. The basics.
AB  - The contractual process for the purchase of a health-care facility information
      system is a major endeavor for today's informatics practitioners as more
      facilities purchase information solution from vendors rather than producing
      proprietary systems. The goal of the contractual process is not simply to protect
      either party from future litigation but to produce a clearly understood document
      that outlines the duties and responsibilities of both the organization and the
      vendor. This document should anticipate and set forth contingencies for problems
      that may arise in the future. Guidelines are offered to assist nurses who are
      members of the acquisition team better understand the contract review process.

PMID- 9014392
TI  - Nurses' attitudes toward computerization in clinical practice in a British
      general hospital.
AB  - The growth of information technology systems associated with the organizational
      reforms of the British Health Service has given rise to a need to understand
      nurses' attitudes toward computerization. Several studies in the United States
      have identified various factors that influence nurses' computer-related attitudes
      but such studies in the United Kingdom are rare. This study sampled 208 nurses in
      a general hospital of approximately 500 beds, and measured their computer-related
      attitudes using Stronge and Brodt's questionnaire. Demographic data specifically
      related to the UK scene also were collected. Although nurses' computer-related
      attitudes generally were positive, significant differences were found in relation
      to age, length of service as a trained nurse, job title, type of nursing unit,
      and length of service at the study hospital. Brodt and Stronge also found
      significant differences related to length of time as a trained nurse and nursing
      unit, but not for length of service or age. Discussion of the study findings
      suggests that the UK scene is not dissimilar to that in the United States.
      However, comparison of findings with Brodt and Stronge's work raises some
      questions about trends in nurses' computer-related attitudes and about the
      usefulness of computer technology to professional nursing practices.

PMID- 9014393
TI  - The computer age impacts nurses.
AB  - The information for this article was collected at the Department of Veterans
      Affairs Domiciliary in White City, Oregon. The intent is to show the transition
      from a paper record to an entirely computerized patient record system and to show
      the impact on nursing practice at the Domiciliary. Clinicians using the paperless
      record have verbalized positive experiences and derived much benefit because of
      easier and quicker access to patient records, thereby allowing more time for
      direct patient care.

PMID- 9014394
TI  - Study on the feasibility of delineating mosquitogenic conditions in and around
      Delhi using Indian Remote Sensing Satellite data.
AB  - A feasibility study to identify mosquitogenic conditions in six study sites in
      and around Delhi (Bhalaswa lake, Nazafgarh drain, Seelampur lake, Sanjay lake,
      Okhla barrage and Hindon barrage) using Indian Remote Sensing Satellites was
      carried out. The water bodies with marshy areas, vegetation and human settlements
      were considered as environmental variables responsible for mosquitogenic
      conditions. Multidate IRS 1A and B, LISS-II satellite data were collected and
      analysed on Vax 11/780 computers. False colour composite (FCC) images were
      generated and land cover assessed using supervised classification based on ground
      truth training sets. Ground truth validation of satellite data was done on
      satellite pass dates. Concurrent monitoring of larval and adult mosquito density
      was performed by selecting sub-sites in each study site. The results indicate
      that mosquitogenic conditions can be identified (with limitation of resolution,
      i.e. 36.5 m) using FCC images and these images can be used as base maps of study
      sites. Characterization of study sites based on land cover was done from the view
      point of mosquitogenic conditions. Spatial changes in mosquito density vis-a-vis
      changes in environmental variables revealed positive correlation with water
      bodies and vegetation in some study sites.

PMID- 9014395
TI  - A study of sensitivity of P. falciparum to chloroquine in a rural area of Bharuch
      district, Gujarat. SEWA-Rural Research Team. Society for Education, Welfare and
      Action.
AB  - A study was undertaken to determine the level of chloroquine sensitivity in P.
      falciparum strains prevalent in a rural, tribal-belt of Bharuch district, Gujarat
      during 1992-93. Of the 32 cases for which the 7-day follow-up was completed, only
      in one RII level of resistance was noted, with the mean parasite clearance time
      in the remaining cases being 1.87 days. Thus, chloroquine continues to be
      effective in treatment on falciparum malaria in this area.

PMID- 9014396
TI  - Blood lipid changes in repeated infections of vivax malaria.
AB  - Alterations in the levels of plasma and erythrocyte membrane lipids in fresh and
      repeated P. vivax malarial patients were studied. A significant fall in plasma
      cholesterol and phospholipids was observed in repeated malaria. The decrease was
      highly significant when the number of attacks were more than five (p < 0.0001). A
      significant increase in plasma triglycerides and non-esterified fatty acids were
      observed when the number of attacks was between 4-5 (p < 0.0001). Erythrocyte
      membrane cholesterol and phospholipids were increased in repeated malaria. The
      increase in erythrocyte membrane cholesterol and phospholipids, was significant
      in more than five attacks (p < 0.0001). The activities of LCAT and LPL were
      decreased significantly in repeated malaria, when the number of attacks were
      between 4-5 (p < 0.0001). It is suggested that repeated malarial attack alters
      the lipid metabolism and the changes are marked with increase in the number of
      malarial attacks.

PMID- 9014397
TI  - Preliminary evaluation of safety aspects of neem oil in kerosene lamp.
AB  - Kerosene lamps containing one per cent neem oil were used for mosquito repellent
      action in a village near Delhi. The safety aspects of this personal protection
      method developed by Malaria Research Centre were evaluated by animal studies and
      clinical examination of population before and after exposure. Single application
      of neem oil (1%) did not produce skin irritation in rabbits and adverse effect on
      guinea pigs after exposure to aerosol. Clinical examination of 156 adults and 110
      children did not reveal any major adverse effects after one year of exposure to
      1% neem oil.

PMID- 9014398
TI  - Application of peptide ELISA in tribal malaria of Madhya Pradesh.
AB  - A recently developed peptide ELISA method was used for monitoring the efficacy of
      malaria control programme in the tribal areas of Madhya Pradesh. Both crude Pf
      antigen and synthetic nonapeptide were used in ELISA for seroepidemiological
      studies. Both antigen responded equally well but the synthetic peptide had
      advantages of purity, defined characteristic and easy availability. Population of
      Mandla protected by vector control measures showed lower antibody titre and lower
      percentage positivity compared to the unprotected population of Jabalpur. A 0-5
      yrs sentinel population from Haldwani almost seronegative has been taken as
      control.

PMID- 9014399
TI  - Seasonal prevalence of common anophelines in Sagar Island.

PMID- 9014400
TI  - A case of Plasmodium malariae infection in the Dooars region of West Bengal,
      India.

PMID- 9014401
TI  - Method to identify products induced by radiosterilization. A study of cefotaxime
      sodium.
AB  - Before the use of radiations to sterilize cefotaxime sodium powder, four new
      products radioinduced must be identified and qualified. They have an apparent
      level of or above 0.1%, at the sterilization dose of 25 kGy and are potentially
      toxic. Their identification is difficult because these products are formed at
      very low concentrations and generally have a structure similar as that of the
      main compound. The method proposed is to irradiate the drug in aqueous solution
      in order to increase the yields in radiolysis products, to compare the retention
      time of the new products, measured by high performance liquid chromatography,
      with those obtained after the irradiation of the solid drug and to identify from
      the aqueous solution the products which are common. One common product was found
      after the irradiation of cefotaxime in solid state and in aqueous solution. It
      was easily identified from the irradiated aqueous solution as anticefotaxime.
      This new product induced by the radiosterilization treatment, is not toxic but
      less active.

PMID- 9014402
TI  - If I heard him right, here's what he said...

PMID- 9014403
TI  - Surgical applications of the laser in the ear and brainstem.

PMID- 9014404
TI  - Rheumatoid arthritis and the pulmonary nodule.
AB  - The potential difficulties offered by the presence of a solitary pulmonary nodule
      in a patient with rheumatoid arthritis are illustrated by a male non-smoker with
      clinical, serologic and radiographic rheumatoid arthritis, active and fibrosing
      alveolitis and a new lung nodule. This nodule proved to be squamous cell
      carcinoma without the typical risk factors. The findings of a solitary pulmonary
      density or nodule in a patient with rheumatoid arthritis provides no assurance
      that the lesion is benign. Both necrobiotic nodules and lung cancer may present
      as solitary pulmonary nodules in patients with this autoimmune disease.

PMID- 9014405
TI  - The Kentucky medical curriculum. A response to the call for educational reform: a
      GPEP report card.
AB  - The resources of an important educational grant provided by the Robert Wood
      Johnson Foundation, as well as designated local college and medical center funds,
      provided support for the renewal of the undergraduate medical education program
      at the University of Kentucky College of Medicine. The fully revised medical
      curriculum, adapted to changing professional and societal needs and completely in
      place by the 1994-95 academic year, was influenced by the recommendations of the
      General Professional Education of the Physician (GPEP) Report, issued by the
      Association of American Medical Colleges in 1984. This paper details each of the
      student-centered curricular changes in the context of the GPEP recommendation
      that it particularly addresses.

PMID- 9014406
TI  - Criticism and medicine.

PMID- 9014407
TI  - Sexual harassment. Work environment policies demand attention.

PMID- 9014409
TI  - A rich medical heritage. Calhoun County physicians have shaped local health care.

PMID- 9014408
TI  - MSMSNET links to medical sites. Physicians' gateway to the information highway.

PMID- 9014410
TI  - Michigan moves toward better pain management.

PMID- 9014411
TI  - Quality pain care key to treating patients. State legislature looks to regulate
      pain management through bills.

PMID- 9014412
TI  - State rep rallies for pain issues. Penny Crissman has first-hand experience.

PMID- 9014413
TI  - MSMS, AMA take proactive stance. Advocate quality pain management techniques.

PMID- 9014414
TI  - Physicians play key role as hospice system grows.

PMID- 9014415
TI  - Voters yell "freeze!" Analysts surmise 1996 elections tell politicians to stay
      the course.

PMID- 9014416
TI  - [Clinical characteristics and trends in research of Parkinson's disease and
      parkinsonism in Japan].
AB  - Parkinson's disease (PD) is one of the major neurological diseases affecting
      elderly subjects. Presumed prevalence of PD is 80-100 per 100 thousands and it is
      estimated that there are approximately 100 thousands patients in Japan. From a
      statistic on age distribution of patients visiting doctors, it is estimated that
      patients with ages at 75-79(639/100,000) and 80-84(632/100,000) are highest in
      number. Juvenile parkinsonism is a syndrome with parkinsonian motor symptoms and
      dystonia developing before and after ten years of age. Reports on this syndrome
      have been accumulated in Japan and gene abnormality in a enzyme relating to
      dopamine metabolism was discovered in the hereditary progressive dystonia with
      marked diurnal fluctuation (Segawa). Among symptomatic parkinsonism,
      cerebrovascular parkinsonism is mainly due to multiple infarction in the basal
      ganglia or Binswanger's disease in Japan, and both conditions develops
      parkinsonism, pseudobulbar palsy and dementia progressively. Diffuse Lewy body
      disease and a unique type of progressive supranuclear palsy presenting a disorder
      designated "pure akinesia" were studied mainly in Japan. In drug therapies of PD,
      it has been argued why the maintenance dose of levodopa or dopamine agonists was
      generally low in Japan. In addition to constitution and drug metabolism, attitude
      of Japanese people to worry side effects more than merit with beneficial effects
      by a drug may have inevitably lead to low maintenance dose. Development of new
      drugs have been undertaken in parallel with US and Europe. Talipexole
      hydrochloride has been on market in Japan recently, but MAO-B inhibitors and COMT
      inhibitors are in final stages to wait evaluations by the governmental committee.

PMID- 9014417
TI  - [Concept and diagnostic criteria of Parkinson's disease and parkinsonism].
AB  - Parkinson's disease (PD) is defined as a neurodegenerative disorder characterized
      pathologically by degeneration of substantia nigra and locus coeruleus with Lewy
      bodies in the remaining neurons and clinically by resting tremor, cogwheel
      rigidity, bradykinesia and loss of postural reflex. Parkinsonism may be defined
      as those who show at lest two of the major four features characterizing PD. We
      propose the following diagnostic criteria for PD, i.e., clinical criteria
      (resting tremor or at least two of the remaining cardinal features of PD),
      treatment criteria (good response to anti-parkinson drugs), image criteria
      (essentially normal cerebral MRI), and exclusion criteria (no history of
      encephalitis or exposure to parkinsonism-inducing substances or drugs). Patients
      must fulfil all four criteria for the diagnosis.

PMID- 9014418
TI  - [Clinical classifications of Parkinson's disease].
AB  - Although typical clinical features of Parkinson's disease are widely accepted,
      the symptoms of individual parkinsonian patient are variable. We reviewed here
      the possible classification of the disease in terms 1) degree of response to
      levodopa, 2) rates of progression, 3) age of onset, and 4) main symptoms. In
      order to select a most appropriate therapeutic drug, we proposed other points for
      classification, 5) development of wearing-off, 6) with or without severe dementia
      and 7) characteristic clinical features, i.e. akinetic form, frozen form and so
      on. For the evaluation of long-term effects of anti-parkinsonian drugs, it is
      important to classify the patients by the course of alteration of cardinal or
      characteristic symptoms.

PMID- 9014419
TI  - [Neural mechanisms for the clinical syndromes of Parkinson's disease].
AB  - The structural organization and neuronal circuit of the basal ganglia were
      reviewed, and the neural mechanisms for the clinical syndromes of Parkinson's
      disease were discussed. Dopamine depletion in parkinsonian patients causes an
      increase in neuronal activities in the globus pallidus internal segment and the
      substantia nigra pars reticulata, resulting in an inhibition of neurons in the
      thalamus and pedunculopontine nucleus, and developing akinesia and rigidity.
      Distorted integral information processes in the striatum and different
      involvement patterns of the two pathways of the information flow, the direct and
      indirect pathways, may cause diversity of the extrapyramidal syndromes in basal
      ganglia diseases. Also discussed was an instructional role of dopamine in
      generating a relevant voluntary movement by modulating the striatal neurons.

PMID- 9014420
TI  - [Neuropathology of the basal ganglia in Parkinson's disease with a special
      reference to its responsible lesion].
AB  - It took approximately one century to discover the neuropathologic lesion
      responsible for Parkinson's disease, of which clinical manifestations were
      originally described in 1817. Namely, the lesion is located in the substantia
      nigra pars compacta and is histologically characterized by loss of pigmented
      nerve cells, formation of Lewy bodies and proliferation of astrocytes. The
      neuronal loss is observed predominantly in the lateral portion of the pars
      compacta, more conspicuously in its ventral region where immunoreactivity to
      tyrosine hydroxylase is also decreased. The formation of Lewy bodies, which are
      found to be peculiar in Parkinson's disease, may hold a clue to the elucidation
      of the mechanism of neuronal degeneration. An animal model induced by MPTP
      stimulates a search for environmental factors capable of initiating the disease.

PMID- 9014421
TI  - [The use of magnetic resonance imaging (MRI) and single photon emission computing
      tomography (SPECT) for the differential diagnosis of Parkinson's disease and
      other neurodegenerative disorders presenting as parkinsonism].
AB  - In Parkinson's disease, both MRI and SPECT are usually normal. In striatonigral
      degeneration and olivo-ponto-cerebellar atrophy presenting as parkinsonism, MRI
      shows putaminal atrophy and SPECT shows hypoperfusion in the frontal lobe, basal
      ganglia and cerebellum. In progressive supranuclear palsy, MRI shows tegmental
      atrophy and SPECT shows hypoperfusion in the frontal lobe with intact cerebellar
      perfusion. In conclusion, MRI and SPECT seem to be useful for the differential
      diagnosis of Parkinson's disease and other neurodegenerative disorders presenting
      as parkinsonism.

PMID- 9014422
TI  - [New therapeutic strategy for Parkinson's disease based on pharmacological
      profiles].
AB  - Although levodopa is the most effective therapeutic agent for Parkinson's disease
      (PD) and has improved the QOL and increased the life expectancy of patients with
      PD, its beneficial effects are not permanent. Long-term levodopa therapy has many
      problems, including wearing-off, on-off phnonena, dyskinesia and psychotic
      symptoms, and has created serious problems for patients with PD. New therapeutic
      strategies are therefore needed to treat patients with PD. Given the well-known
      imbalance between dopaminergic and cholinergic activities in brain of PD
      patients, recent drug therapy has consisted of a multi-drug regimen, with low
      doses of levodopa, dopamine agonists, amantadine and anti-cholinergics. The most
      important is combination therapy with a dopamine agonist and low dose levodopa.
      This combination therapy is likely to create a better balance between
      postsynaptic D2- and D1-receptors and to maintain a normal dopamine
      neurotransmission for longer periods.

PMID- 9014423
TI  - [Guidelines of drug therapies for Parkinson's disease].
AB  - Treatment of Parkinson's disease has progressed steadily for the last decades
      after introduction of levodopa. For recovery of striatal dysfunction caused by
      loss of projecting nigral cells, supplementation of neurotransmitter dopamine
      (DA), facilitation of neural transmission by DA agonists and amantadine,
      suppression of acetyl-choline neurons, having antagonistic action to DA cells,
      are all effective especially at the early to middle stages of illness. As
      prevention of neuronal cell death in parkinsonian brain has not yet been
      succeeded, difficulties in treatment with symptom fluctuation and CNS side
      effects such as dyskinesia or psychic symptoms develop inevitably in the long
      course of evodopa treatment. Proper choice of drugs for parkinsonian core and
      accompanying symptoms and selection of methods of medication for maintenance of
      natural daily life activities are necessary for attainment of good QOL for whole
      time course of the disease.

PMID- 9014424
TI  - [Treatment of Parkinson's disease with multiple drugs].
AB  - All major symptoms of Parkinson's disease, i.e., rigidity, tremor, hypokinesia
      and postural instability are induced by an impaired dopaminergic
      neurotransmission in the nigro-striatal pathway. Levodopa pioneered the
      symptomatic therapy of Parkinson's disease. While it is effective on the motor
      symptoms, long-term levodopa therapy often results in dyskinesia, motor
      fluctuations and psychosis. Coadministration of levodopa and dopamine agonists,
      bromocriptine and pergolide, decreases these adverse side effects.
      Anticholinergics and amantadine are often effective as adjuvant drugs for the
      early stage of patients with Parkinson's disease. Furthermore, L-threo-DOPS, nor
      adrenergic precursor drug, is sometimes effective for the advanced stage of
      Parkinson's disease. Thus coadministration of multiple antiparkinsonian drugs,
      rather than single therapy of levodopa, is useful for the long-term treatment of
      Parkinson's disease.

PMID- 9014425
TI  - [Problems of long-term levodopa therapy in Parkinson's disease].
AB  - It has been clarified that long-term levodopa therapy in Parkinson's disease may
      pose various serious problems of adverse reactions, such as dyskinesia, wearing
      off effect, on-off effect, mental symptoms, and frozen gait. At our department,
      dyskinesia, wearing-off effect, on-off effect, mental symptoms and frozen gait
      were respectively noted in 29 (11.2%), 78(30.0%), 17(6.5%), 42(16.2%), and
      51(19.6%) of 260 patients with Parkinson's disease who had been administered
      levodopa for over one year. In the statistical investigation by the multiple
      analysis, the time from first onset to initiation on levodopa therapy or the
      duration of levodopa therapy was not closely related to the development of any
      adverse reaction, while Hoehn and Yahr's stage and dosage levodopa had the most
      significant influence on the development of adverse reactions. Therefore,
      levodopa therapy may not be an important risk factor of adverse reactions even
      when it is started early after the onset of Parkinson's disease. In order to
      prevent adverse reactions to long-term levodopa therapy in Parkinson's disease,
      it is important to minimize the dose of this drug even when it is administered in
      combination with multiple anti-Parkinsonism drugs.

PMID- 9014426
TI  - [Definition and nosological concept of juvenile parkinsonism].
AB  - Clinicopathological identification of juvenile parkinsonism(JP) was described in
      reference to Dopa-responsive syndrome or to dopamine-dependent disorders.
      Recently, hereditary progressive dystonia(HPD), a dopamine-dependent disorder,
      was identified as a nosological entity from JP and Parkinson's disease(PD) by
      discovery of mutations of the gene. JP includes young onset Parkinson's
      disease(YOPD) and idiopathic JP with much younger-onset cases. YOPD belongs to PD
      nosology based on clinical and pathological findings of our own autopsied cases.
      However, the idiopathic JP' might involve independent pathophysiological changes.
      Namely, cases of the JP are associated with atypical pathological findings with
      lack of Lewy body or hypoplasia of the substantia nigra and specific clinical
      manifestations of autosomal recessive trait and of dystonic feature and diurnal
      fluctuation of the symptoms.

PMID- 9014427
TI  - [Clinical characteristics and linkage analysis of autosomal recessive form of
      juvenile parkinsonism(AR-JP)].
AB  - We present the clinical characteristics of autosomal recessive form of juvenile
      parkinsonism(AR-JP) (MIM 600116) and the result of the linkage analysis using 11
      markers on the long arm of chromosome 6. We examined 25 patients of 13 Japanese
      AR-JP families. They showed female predominance, mean age at onset at 24.4 +/-
      10.3 years, slow progression, good response to levodopa and frequent occurrence
      of wearing-off phenomenon and dopa-induced dyskinesia. Compared to Parkinson's
      disease(PD), the parkinsonian triad(tremor, rigidity and bradykinesia) were mild,
      but dystonic posture, postural instability and hyperreflexia were more prominent
      compared to PD. By the linkage analysis, we obtained a strong evidence for
      linkage of the AR-JP gene to a 17 cM region of chromosome 6q25.2-27 including the
      Mn-superoxide dismutase gene(SOD2) with a maximal cumulative multipoint lod score
      of 9.44 at 0.9 cM telomeric to D6S253.

PMID- 9014428
TI  - [PET study of dopamine metabolism and dopamine D2 receptor in juvenile
      parkinsonism].
AB  - Positron emission tomographic(PET) study using 18F-6-fluoro-L-dopa (18FDOPA) can
      provide efficient information on the pre-synaptic function of nigrostriatal
      dopaminergic neurons. In juvenile parkinsonism(JP), the accumulation of 18FDOPA
      is markedly decreased in the caudate nucleus and putamen on both hemispheres.
      This finding is different from those in dystonia syndromes such as dopa
      responsive dystonia (DRD) and hereditary progressive dystonia with marked diurnal
      fluctuation(HPD), and it is rather similar to late onset of Parkinson's disease.
      Furthermore, we studied dopamine D2 receptor binding activity on the post
      synaptic sites of the striatum using 11C-YM-09151-2(11C-YM), a highly selective
      dopamine D2 receptor antagonist. In JP, 11C-YM was highly accumulated in the
      striatum, and D2 receptor binding activity is not significantly different from
      that of age-matched young normal subjects, but much higher than that of aged
      subjects. This finding suggests that post-synaptic dopamine receptor function
      keeps still normal or hypersensitive in JP, and may be different from other
      degenerative disorders such as multiple system atrophy. Glucose metabolism using
      18F-fluoro-2-deoxy-D-glucose(18FDG) was also within normal range in the cerebral
      cortex in JP, but was more increased in the striatum than in the cerebral cortex
      in some patients. These PET studies can provide efficient informations about the
      pathologic condition of JP.

PMID- 9014429
TI  - [Glucose metabolism and blood flow studies in 2 cases with juvenile Parkinson's
      disease].
AB  - Cerebral glucose metabolism at resting state and blood flows during resting
      state, during finger-movement, and during finger-brushing stimulation were
      measured in two cases with juvenile Parkinson's disease(Narabayashi) with PET.
      Major symptom was rigidity and hypokinesia in both cases. Glucose metabolism was
      reduced in frontal cortex and increased at striatum. In one case with it
      pallidotomy 1 year before glucose metabolism was more reduced over entire it
      hemisphere including striatum than the right without any additional symptoms
      after the surgery. Blood flow was increased during 2 tasks and focal increase
      patterns were different from those in normal volunteers. Classical glucose
      metabolism and blood flow studies are still useful in this disorder.

PMID- 9014430
TI  - [Treatment and prognosis of juvenile parkinsonism--L-dopa responsiveness].
AB  - The treatment and prognosis of juvenile parkinsonism(JP) with onset under the age
      of 40 years is described. The patients with JP responded better to L-dopa and
      more gradual progression of symptoms, but, developed dopa-induced dyskinesias and
      motor fluctuations earlier and more frequently than Parkinson's disease patients.
      In order to control the dyskinesias and motor fluctuations, a small dose of L
      dopa has to be administered several times a day with the combination of dopamine
      receptor agonists. As a result of the increased life expectancy with L-dopa
      treatment the mean duration of the disease has increased in Parkinson's disease
      and JP, however, mean age at death in JP was still under 60.

PMID- 9014431
TI  - [Vascular parkinsonism].
AB  - Critchley speculated that multiple vascular lesions of the basal ganglia must
      have an etiological connection to the symptoms of so-called vascular parkinsonism
      (VP), but without neuropathological confirmation. Some had doubts about its
      existence because of the lack of the pathologically confirmed case with adequate
      clinical correlation. At present, VP is characterized clinically by the short
      stepped or frozen gait, lead-pipe rigidity, the symmetry of findings, absence of
      resting tremor, and negative response to levodopa in elderly patients with
      cerebrovascular lesions on CT/MRI. Pseudobulbar palsies, pyramidal tract
      findings, and/or multi-infarct dementia coexist in some of the cases. Most of
      clinically suspected VP patients have cerebral white matter lesions as well as
      basal ganglia lesions.

PMID- 9014432
TI  - [Drug-induced parkinsonism].
AB  - Drug-induced parkinsonism(DIP) is at present the second most frequent cause of
      parkinsonism next to idiopathic Parkinson's disease(PD) in Japan. The ratio of
      the incidence of DIP to PD has been reported to be between 1:2 and 1:5, which
      varied at the period surveyed. The most frequent causative drugs were calcium
      blocking agents, flunarizine and cinnarizine in 1980s, and they have been
      replaced in recent years by benzamide derivatives with antipsychotic, antiemetic
      or prokinetic actions, sulpiride, tiapride and metoclopraramide. The clinical
      features of DIP are similar to those of PD except for rather rapid progression of
      the symptoms. Careful neurological examination and check of all drugs the patient
      has taken are important for correct diagnosis. Most causative drugs act as the
      dopamine D2 receptor blocker in the brain and discontinuance of the drug(s) is
      necessary for the treatment. Parkinsonian symptoms begin to improve in several
      weeks and patients are relieved from the symptoms usually within several months.

PMID- 9014433
TI  - [Brain tumor and parkinsonism].
AB  - Reports on cases of parkinsonism associated with brain tumor were reviewed.
      Although parkinsonism can develop in association with any type of brain tumor, it
      develops most frequently in association with meningiomas located at the sphenoid
      ridge or frontal convexity. Although parkinsonian symptoms in the parkinsonism
      associated with brain tumors are similar to those seen in Parkinson's disease in
      the early stages, atypical symptoms, such as visual field defects, motor weakness
      or pyramidal signs are visible signs of the parkinsonism. Functional abnormality
      in the nigrostrial system due to chronic mechanical compression of the system by
      a sizeable brain tumor seems to contribute to the pathogenesis of the
      parkinsonism.

PMID- 9014434
TI  - [Striatonigral degeneration].
AB  - Striatonigral degeneration (SND) is sporadic, middle-aged on set degenerative
      disease of the nervous system which etiology is unknown. SND is considered one of
      multiple system atrophy (MSA). Clinically parkinsonian symptom is dominant and
      then it is difficult to distinguish from idiopathic Parkinson's disease (PD).
      Pathologically neuron cell loss and gliosis are recognized principally striatum
      (mainly putamen) and substantia nigra. Putaminal hypointensity and slit-hyper
      intensity in the outer margin of putamen are often seen on T2-weighted 1.5 Tesla
      MRI. PET with [18 F] fluorodeoxyglucose indicates a considerably decreased
      glucose utilisation in the striatum of SND, whereas glucose utilisation are
      normal in PD. Striatal dopamine D1, D2 receptors are reduced. Response to
      Levodopa is poor or absent.

PMID- 9014435
TI  - [Progressive supranuclear palsy].
AB  - Progressive supranuclear palsy (PSP) is a distinct clinicopathological syndrome
      described by Steele, Richardson and Olszewski in 1964. Its clinical features
      include supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria, nuchal
      dystonia, and dementia. The neuropathological changes are characteristic and
      include cell loss, gliosis, and neurofibrillary degeneration in the basal
      ganglia, brain stem and cerebellum. But, all these clinical features are not
      present in the early stage and diagnosis of PSP is sometimes difficult. Atypical
      presentation of PSP includes the case without ophthalmoplegia, with markedly
      dementia, or pure akinesia. Pure akinesia presents freezing of gait, handwriting
      and speech without rigidity or tremor, and can be the initial and early symptom
      complex of PSP.

PMID- 9014436
TI  - [Shy-Drager syndrome and multiple system atrophy].
AB  - Shy-Drager syndrome (SDS) is a subtype of multiple system atrophy (MSA) with the
      clinical predominance of autonomic failure. The differential diagnosis between
      SDS and Parkinson's disease (PD) can sometimes be difficult clinically. The
      features favoring a clinical diagnosis of SDS are marked orthostatic hypotension,
      erectile impotence in males, urinary symptoms, nocturnal stridor, rigidity and
      akinesia without tremors, levodopa unresponsiveness, cerebellar signs, cerebellar
      atrophy on brain CT scans and MRI.

PMID- 9014437
TI  - [Hereditary progressive dystonia with marked diurnal fluctuation--clinical
      features and GTP cyclohydrolase I gene mutations].
AB  - Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a
      disorder characterized by childhood-onset dystonia and a dramatic and sustained
      response to low doses of levodopa. Recently the GTP cyclohydrolase I(GCH-I) gene
      was isolated as the first causative gene for HPD. We analyzed the GCH-I gene in 8
      clinically diagnosed HPD patients and found different point mutations in GCH-I
      gene in 3 subjects. The clinical features of these patients considerably
      resembled each other. Our results imply that although clinically diagnosed HPD
      subjects could present diverse symptoms, patients with a mutant GCH-I gene might
      share homogeneous clinical manifestations.

PMID- 9014438
TI  - [Cortico-basal degeneration].
AB  - Corticobasal degeneration (CBD) is not rare disease, because in our clinic 13
      patients were observed for the past 8 years, with ratio to those with Parkinson's
      disease being 1:18. Our clinical criteria of this disease consist of the
      combination of 1) limb-kinetic apraxia as cortical sign, 2) akinetic-rigid sign
      as extrapyramidal sign, 3) their marked asymmetry, and as additional findings, 4)
      the presence of grasp reflex, alien hand sign, reflex myoclonus, limb dystonia,
      and others, and 5) neuroimagings (MRI, SPECT) suggestive of asymmetric cortical
      lesions. There are reports indicating that clinical CBD was diagnosed as Pick's
      disease, progressive supranuclear palsy and Alzheimer's disease, pathologically.
      Therefore, more basic investigations, especially from molecular biology are
      necessary to discriminate these corticobasal complex disorders.

PMID- 9014439
TI  - [Diffuse Lewy body disease].
AB  - I reviewed the clinical symptoms and neuropathologic findings of diffuse Lewy
      body disease (DLBD). The cardinal symptoms of DLBD are parkinsonian symptoms and
      dementia. Parkinsonian symptoms are similar to those of Parkinson's disease
      except for lower frequency and mild degree of tremor. Dementia becomes the
      initial symptom especially in elderly patients, and is composed of symptoms of
      cortical dementia. As neuropathologic findings, there are cortical Lewy bodies
      mainly observed in the temporal cortex, insular cortex, cingulate cortex, and
      amygdala with or without senile changes, besides brain stem findings as
      Parkinson's disease. For prompt diagnosis of DLBD, we should pay more attention
      to the clinical and neuropathologic symptoms and signs of this disease, which may
      be encountered more frequently in the future.

PMID- 9014440
TI  - [Parkinsonism in Alzheimer's disease].
AB  - Parkinsonism occurs frequently in the patients with Alzheimer type dementia
      (ATD). The frequency ranges from 9% to 100% of ATD patients, depending on
      samples, clinical instruments and stages of illness. Several studies have
      described that rigidity and hypokinesia are the most prevalently observed signs
      of parkinsonism, and that resting tremor is less. The clinical progress of
      patients with parkinsonism is more rapid than those of patients without
      parkinsonism. Patients with parkinsonism are frequently associated with
      psychiatric symptoms such as depression and delusion. The pathogenesis of
      parkinsonism in ATD remains to be elucidated, but it should be noted that some
      cases with parkinsonism correlates with Parkinson's disease pathologic condition,
      and some have diffuse Lewy body disease.

PMID- 9014441
TI  - [Objective measurement of motor activity in Parkinson's disease by actigraphy.
      Clinical assessment of akinesia].
AB  - Actigraphy measures physiological activity by using an acceleration sensor and
      RAM equipped with a data logger. Since actigraphy can continuously and easily
      record data over a long period of time without disturbing the normal activities
      of subjects, it is possible to analyze a large number of subjects. Actigraphy was
      performed in patients with Parkinson's disease who did not exhibit trembling.
      Results showed that the daily motor activity of patients was lower than that of
      the healthy individual. Daily motor activity was also found to be correlated with
      Hoehn-Yahr's classification. Furthermore, side-effects due to L-dopa, such as
      abnormal involuntary movement and on-off phenomenon, could be objective assessed.
      The results of long-term actigraphic examination, conducted after anti
      Parkinsonian treatment, showed that akinesia improved with time. From these
      findings, it is concluded that actigraphy could quantitatively assess the degree
      of akinesia in Parkinsonian patients. Furthermore, actigraphy may be applied to
      the clinical assessment of drugs.

PMID- 9014442
TI  - [Clinicophysiological study of tremor in Parkinson's disease: quantitative tremor
      based assessment of motor count using actigraphy].
AB  - In Parkinson's disease, resting tremor is often the initial symptom. This report
      focuses on the mechanism underlying tremor in Parkinson's disease and
      quantitative assessment of tremor. Central factors including Vim (nucleus
      ventralis intermedius) in the thalamus, and peripheral factors, such as
      acceleration of input pathways from muscle spindles via muscle tonus, are
      important aspects of the tremor mechanism in Parkinson's disease. It has also
      been suggested that tremor in Parkinson's disease is associated with
      parasympathetic and sympathetic dysfunctions. Objective assessments of tremor,
      such as the application of surface electromyography, are useful in the diagnosis
      and treatment of Parkinson's disease. Actigraph, as introduced herein, is a three
      dimensional motor sensing apparatus. Therefore, motor counts over 0.01 G can be
      detected by actigraphy. To date, this device has been used for evaluating
      akinesia in Parkinson's disease and insomnia. In this study, actigraphy was used
      in Parkinson patients with tremor, and it reflected motor activity in the wrist
      and was associated with the severity of hand tremor. Activities of daily living
      (ADL) are disturbed by hyperkinesia of the hand for Parkinson patients with hand
      tremor. We demonstrated that actigraphy is a simple and quantitative method of
      assessing motor activity in Parkinson patients with tremor.

PMID- 9014443
TI  - [Kinematic and EMG pattern of parkinsonian gait].
AB  - To clarify characteristic pattern of parkinsonian gait, gait analysis was
      performed by measuring floor reaction forces, angular displacements, and surface
      electromyograms on patients with Parkinson's disease (PD) and normal controls. PD
      patients walked with slow speed, shortened stride, prolonged double support
      period, and restricted movement of the hip, knee, and ankle joints. Muscle
      activity of the gastrocnemius and tibialis anterior muscles reduced, and
      correspondingly pressures for step-in and kick-off decreased. These changes were
      correlated with severity of clinical scale. Despite these alterations, reciprocal
      activity of the distal antagonistic muscles was preserved. We conclude that these
      characteristic alterations reflect distorted mechanisms for gait control in PD
      and could be one of useful parameters for evaluation of pathophysiology of
      parkinsonian gait.

PMID- 9014444
TI  - [A physiological study on instability in Parkinson's disease].
AB  - To clarify roles of impairment of proprioceptive reflexes in instability of
      parkinsonian gait, delta EMG/delta angle of the gastrocnemius and tibialis
      anterior muscles was measured during the stance phase on patients with
      Parkinson's disease and normal controls. This ratio decreased in the
      gastrocnemius muscle, while it was unchanged in the tibialis anterior muscle.
      delta EMG/delta angle is likely to be correlated with muscle stiffness(delta
      muscle force/delta muscle length) that reflects from stretch reflexes. Thus our
      results suggest an impairment of stretch reflexes of the extensor muscle during
      parkinsonian gait.

PMID- 9014445
TI  - [Central motor conduction time using magnetic and vibratory stimulation in
      Parkinson's disease, especially in patients with rigidity].
AB  - Rigidity, tremor, akinesia and disorder of postural reflex are the main clinical
      features of Parkinson's disease. We presented the mechanism underlying rigidity
      and assessed central motor conduction time (CMCT) using magnetic, with or without
      vibratory, stimulations. Basal ganglia, especially, the internal pallidum, and
      the thalamus play major roles in the mechanism of rigidity in Parkinson's
      disease. Hyperexcitability of the spinal motor nucleus due to low threshold has
      been recognized. Magnetic stimulation is painless and is simpler than electric
      stimulation. Therefore, this method is used clinically for evaluating conduction
      disturbance of the upper motor neurons in multiple sclerosis, cerebrovascular
      disease and so on. CMCT measured by magnetic and/or electric stimulation may be
      abbreviated or normal in Parkinson's disease, according to the literature, though
      controversy persists in this regard. In our study, CMCT was normal in Parkinson
      patients. However, CMCT was reduced in patients with rigidity and tremor.
      Furthermore, in a portion of the patients, CMCT was further abbreviated by also
      applying vibratory stimulation. These observations support the hypothesis that
      cells in the thalamus, cortex and spinal cord and/or pathways in these portions
      of the central nervous system are excitable or activated in Parkinson patients
      with rigidity and tremor. However, elucidation of the mechanisms underlying
      rigidity and tremor awaits further investigation.

PMID- 9014446
TI  - [Impaired associated movement in Parkinson's disease].
AB  - We analyzed the intended voluntary movement and simultaneously occurring
      automatic associated movement in Parkinson's disease(PD). We studied wrist
      dorsiflexion as a movement associated with grip and Bell's phenomenon(upward
      rolling of the eyeballs on forcible closure of the eyelids) in patients with PD
      and normal controls. The patients showed significantly smaller wrist dorsiflexion
      and upward rolling of the eyeballs. Patients with PD have a greater reduction of
      automatic associated movement than intended voluntary movement. This discrepancy
      between the associated movement and voluntary movement may be one of the bases of
      clinical symptoms of PD patients in early stage.

PMID- 9014447
TI  - [Movement-related cortical potentials upon forward-stepping in patients with
      Parkinson disease].
AB  - We investigated movement-related cortical potentials(MRCPs) in 20 patients with
      Parkinson disease(PD group) and 6 normal age-matched controls when they were
      stepping forward volitionally from standing position. PD group was divided in
      three groups according to the clinical courses and motor function scores in
      Langston's criteria: Ia; within 6 years and higher than 20 points, Ib; within 6
      years and within 20 points, II; over 6 years. In Ia group their negative
      slope(NS') was larger than those in the other three groups, while their
      Bereitschaftspotential showed no statistical difference. The results of our
      investigation shows that, in these cases, the function of cerebral cortex and/or
      cerebellum can be enhanced compensating the dysfunction of basal ganglia.

PMID- 9014448
TI  - [Cognitive impairment in Parkinson's disease--a visual event-related potential
      study].
AB  - The visual event-related potentials(ERPs) in Parkinson's disease(PD) are
      reviewed. In patients with demented PD, the task-relevant P3(P3b, target P3)
      latency is significantly prolonged compared with the control, while patients with
      nondemented PD show inconsistent results, probably due to the difference in
      experimental procedure or antiparkinsonian medication. The task-irrelevant
      P3(P3a, nontarget P3) latency under conditions of passive attention is not
      prolonged in PD regardless of the presence of dementia. The results of P3
      amplitudes remain controversial. The N2 latency is delayed compared to the
      control during the semantic discrimination task, although there is no difference
      in NA latency. The attenuation in the CNV(contingent negative variation)
      amplitude is found in PD patients, probably due to the impairment, either in
      maintaining their attention or preparing the response.

PMID- 9014449
TI  - [Deficit of explicit memory in Parkinson's disease demonstrated by auditory
      verbal and visual-design learning tasks].
AB  - This study is concerned with explicit memory in both auditory and visual
      modalities in patients with non-demented(on DSM-III-R) Parkinson's disease. On
      some explicit memory studies, Parkinsonian patients were compared with normal
      controls matched for age and education. For assessment of recollection, recall
      and recognition were assessed using two clinical test batteries, Rey's Auditory
      Verbal Learning Test and Rey's Visual-Design Learning Test. In addition to a
      comparison of recall and recognition, the present research inquired into the
      serial position data in free recall, analysis by applying a signal detection
      theory to the recognition data, and metamemory by using self-assessment of
      recognition. The results showed that the Parkinsonian group was significantly
      impaired on both tests of free recall compared to the normal controls. By
      contrast, when given tests of recognition memory for the same lists, their
      performance was almost identical only in assessment of correct scores(hits).
      There was a significant correlations between performances on achieved categories
      of the Wisconsin Card Sorting Test and on free recalls of the auditory-verbal
      learning test in the patient group. In recall, no qualitative differences of the
      serial position curves were observed between the two groups, as an increasing
      pattern of primacy and recency effect was preserved. In addition, the two groups
      performed equally well on both auditory (digit span) and visual(spatial span)
      short-term memory assessment. Moreover, on the trial-recall curves, from the
      first trial to the last two groups showed no significant differences in their
      learning effect and forgetting. Irrespective of modalities, however, the
      Parkinsonian group recalled less than the controls in the first trials. The poor
      performance of recall in the patients could be explained in terms of diminished
      attentional resources of the central executive system processing information
      beyond their short-term memory span within the framework of Baddeley's model of
      working memory which simultaneously controls two functions of encoding and
      retention. It was suggested that diminished central resources would be strongly
      associated with basal frontal dysfunction in Parkinson's disease. When
      recognition memory was further investigated, false alarms but not misses
      significantly increased despite normal hits in the patients on both tests.
      Analysis by using a signal detection theory produced significant differences, in
      that the Parkinsonian patients had lower values of beta and d' on auditory-verbal
      learning while they had lower tendency of beta on visual-design. The trend that
      they fell into errors by recognizing a distracter as the target presented
      previously was likely to be related a dysfunction of the supervisory system of
      Norman and Shallice's model which was assumed to be in the prefrontal cortex.
      Moreover, the present research disclosed that metamemory, i.e. the ability to
      assess their own memory, was disturbed in the Parkinsonian patients. In addition
      to the problem of recognition mentioned above, it was suggested that the impaired
      metamemory could be attributed to a deterioration of frontal lobe function.

PMID- 9014450
TI  - [Total defect of metaiodobenzylguanidine (MIBG) imaging on heart in Parkinson's
      disease: assessment of cardiac sympathetic denervation].
AB  - This study was conducted to evaluate sympathetic cardiac innervation using MIBG
      imaging in PD. Uptake of MIBG was measured in 35 PD patients. Although normal
      MIBG uptake was observed in PD patients with HY stage l, PD with stage 3-5
      revealed a total defect of visual MIBG imaging on heart area. Quantitative
      measurements of MIBG uptake assessed by the radioactivity ratio of cardiac to
      mediastinal tissue(H/ M) in early imaging was associated with the clinical
      severity of PD(control; 2.0 +/- 0.3, stage l; 2.0 +/- 0.1, stage 2; 1.6 +/- 0.4,
      stage 3-5; 1.3 +/- 0.1). In conclusion, homogeneous impairment of sympathetic
      cardiac innervation was observed in PD patients and this abnormality was
      associated with the clinical severity of PD, indicating that MIBG imaging of
      heart is useful not only for the evaluation of cardiac sympathetic impairment of
      PD but also for the diagnosis of PD.

PMID- 9014451
TI  - [Levodopa loading test as an early marker of Parkinson's disease].
AB  - We report levodopa absorption profile in 8 patients with early stage Parkinson's
      disease(PD) and in 8 age-matched normal control(NC) subjects; the gastric
      emptying time(GET) was also studied simultaneously. Patients with PD showed a
      significantly higher peak plasma levodopa concentration, however, no significant
      difference was present in the GET between the two groups; therefore, the higher
      plasma levodopa peak could not be ascribed to the difference in the GET. In the
      NC subjects, plasma peak levodopa level was positively correlated with the GET,
      however, inverse correlation was observed in the PD patients, suggesting the
      presence of qualitative difference in the levodopa absorption mechanism between
      early PD and normal population. Enhanced levodopa absorption may be a useful
      early marker for PD.

PMID- 9014452
TI  - [PET study using 6-[18F]-fluorodopa in Parkinson's disease].
AB  - 6-[18F]-fluorodopa (FDOPA) was developed as an analogue of L-DOPA across the
      blood-brain-barrier and to carry into nigrostriatal dopaminergic neurons. PET
      study using FDOPA revealed presynaptic dopaminergic function in the striatum of
      nigrostriatal system of the human brain and many studies have performed to
      clarify the pathogenesis of Parkinson's disease. FDOPA is also an efficient
      tracer to analyze pharmacokinetics of L-DOPA by measuring radioactivities of its
      metabolites in the peripheral blood by HPLC and to evaluate pharmacological
      effects on dopamine metabolism by pretreatment of dopa decarboxylase inhibitor or
      COMT inhibitor. PET study using FDOPA is useful not only to diagnose Parkinson's
      disease but also to differentiate from parkinsonism in combination with other
      radioactive ligands and with other neuroimaging methods such as MRI.

PMID- 9014453
TI  - [Cerebral perfusion and oxygen metabolism in Parkinson's disease: positron
      emission tomographic study using oxygen-15-labeled CO2 and O2].
AB  - In many previous studies, positron emission tomography (PET) has been used to
      evaluate cerebral perfusion and oxygen metabolism in Parkinson's disease. In this
      article, these previous reports are reviewed together with our recent findings.
      Hypoperfusion and hypometabolism in parkinsonian brains reported previously
      seemed to be derived chiefly from psychiatric manifestations, including
      intellectual decline and depression. In our study on 34 patients with asymmetric
      symptoms, the blood flow and oxygen metabolism were significantly higher in the
      caudate head and putamen, contralateral to the predominant patient's symptoms,
      than in the opposite nuclei. The asymmetry in the perfusion and metabolism is
      clearer in the early stage of the disease or in patients without DOPA therapy.
      These findings suggest that the striatal dysfunction is caused by uninhibited
      activities, supersensitivities, or compensatory hyperactivities of the striatum.

PMID- 9014454
TI  - [18F-fluorodeoxyglucose positron emission tomography in Parkinson's disease].
AB  - Positron emission topographic studies on local cerebral glucose metabolism in
      Parkinson's disease (PD) including our own data were reviewed. In our 18F-FDG PET
      studies, local or global metabolic change was not found in 9 patients with non
      demented PD, with respect to 5 normal controls. Moreover, there was not an
      apparent difference between severe PD group (Hoehn-Yahr III-IV) and mild PD group
      (Hoehn-Yahr I-II). In other PD patients with dementia or autonomic failure,
      parietal dominant hypometabolism was found likely to those of Alzheimer disease,
      but lenticular nucleus was well preserved. Furthermore 18F-FDG PET findings of
      atypical parkinsonian syndromes, such as SND and PSP were reviewed. They showed
      relative hypometabolism in the basal ganglia in PET images. PET study with FDG
      provides a clue to differential diagnosis of parkinsonian patients.

PMID- 9014455
TI  - [Striatal dopamine D2 receptor in Parkinson disease and its related disorders
      assessed by C-11 NMSP and PET].
AB  - Dopamine D2 receptor binding potential (BP) was measured by C-11 N
      methylspiperone (NMSP) and PET in normal healthy volunteers and patients with
      various neurodegenerative diseases including Parkinson disease (PD), multiple
      system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal
      degeneration (CBD), Huntington disease (HD) and so on. In normal aging process,
      striatal BP was decreased according to the age. In never-medicated Parkinson
      disease, BP was slightly elevated, which may reflect denervation hypersensitivity
      in postsynaptic site. In contrast, BP was reduced in MSA (SND type) and HD. C-11
      NMSP and PET is useful in better understanding of pathophysiology and
      differential diagnosis of Parkinson disease and its related disorders.

PMID- 9014456
TI  - [Muscarinic cholinergic receptor imaging of parkinsonian brain using 11C-NMPB and
      PET].
AB  - 11C-NMPB is a useful ligand which is used to measure brain muscarinic cholinergic
      receptors (mAChRs) for its high affinity and high brain uptake. PET images of 11C
      NMPB uptake had the highest accumulations in the cerebral cortex and striatum and
      the lowest in the cerebellum, both in patients with Parkinson's disease (PD) and
      normal subjects. 11C-NMPB uptake was homogeneous throughout the cerebral cortex
      in the normal subjects but greater in the frontal cortex of about one half of the
      PD patients as compared with other cerebral cortical areas. Quantitative analysis
      showed that the PD patients had high K3 values, an index of mAChR binding, in the
      frontal cortex. In PD, increased mAChR binding in the frontal cortex may be
      related to frontal lobe dysfunction. This technique should prove useful for
      detecting subclinical impairment of the central cholinergic system in PD.

PMID- 9014457
TI  - [Analysis of Parkinson's disease and related syndromes using 123I-IMP-SPECT with
      the ARG method].
AB  - We studied regional cerebral blood flow (rCBF) in 8 patients with non-demented
      Parkinson's disease (PD). 1 patient with progressive supranuclear palsy (PSP), 1
      patient with multiple system atrophy (MSA), and 7 normal control subjects using
      single photon emission computed tomography (SPECT) with the IMP-ARG method.
      Regions of interest were studied in the cerebral cortex (upper frontal, lower
      frontal, temporal, occipital, parietal), thalamus, basal ganglia, and cerebellum.
      In patients with PD, rCBF was normal in 4/8, and decreased in occipital lobe in
      4/8. In patient with PSP, rCBF was decreased in the upper and lower frontal
      lobes, and in the cerebellum. In patient with MSA, rCBF was diminished in the
      cerebellum. The results of our study were almost compatible with the conventional
      rCBF study by positron emission tomography (PET), however, the decrease of rCBF
      in occipital lobe had rarely been reported, suggesting that might be related to
      visuospatial dysfunction in Parkinson's disease.

PMID- 9014458
TI  - [Evaluation of benzodiazepine receptor in the cerebral cortex of Parkinson's
      disease using 123I-iomazenil SPECT].
AB  - 123I-iomazenil is a partial inverse agonist of central-type benzodiazepine
      receptors (BZRs). BZR and the gamma-aminobutylic acid(GABA) receptor comprise a
      receptor complex in the cerebral cortex. Therefore, 123I-iomazenil SPECT will
      provide indirect information of the GABA receptor. Since the GABA-ergic system
      has been reported to modulate the dopaminergic system, the impairment of GABA/BZR
      may affect parkinsonian symptoms. However, there are few reports on Parkinson's
      disease(PD) regarding the impairment of GABA/BZR in the cerebral cortex. We found
      a correlation between motor disability and decrease in 123I-iomazenil uptake in
      the cerebral cortex, suggesting that BZR in the cerebral cortex of patients with
      PD may be impaired in proportion to the severity of the disease. In addition, the
      123I-iomazenil image is, in part, different from the perfusion image. Therefore,
      123I-iomazenil SPECT may give an additional information on the pathophysiology of
      PD.

PMID- 9014459
TI  - [Magnetic resonance spectroscopy in Parkinson's disease and multiple system
      atrophy].
AB  - Recent advances in magnetic resonance spectroscopy(MRS) allow to assay
      noninvasively key molecules of brain metabolism in living patients. There are
      several reports of MRS in Parkinson's disease(PD) and multiple system
      atrophy(MSA). 1H-MRS of the striatum revealed the reduced NAA/Cr and Cho/Cr ratio
      in MSA patients and the preserved NAA/Cr and Cho/Cr ratio in PD patients. The
      reduced NAA/Cr ratio probably reflects striatal neuronal loss. 1H-MRS of the
      striatum showed increased Cho/Cr ratio in the "on" state compared with that in
      the "off" state in the PD patients. The increased Cho/Cr ratio may reflect some
      membrane alteration or change of choline metabolism in PD with the "wearing-off"
      phenomena. Although studies are still preliminary, MRS shows great possibility
      for aiding in the differential diagnosis of parkinsonism and it will contribute
      to a better understanding of the pathogenesis of PD and MSA.

PMID- 9014460
TI  - [31P magnetic resonance spectroscopy(MRS) study in basal ganglia of patients with
      Parkinson's disease].
AB  - We report 31P magnetic resonance spectroscopy(MRS) to study regional high energy
      phosphate and phospholipid metabolism in basal ganglia of patients with
      Parkinson's disease(PD) in comparison with normal controls. The ratio of
      phosphomonoester(PME)/phosphocreatine(PCr), phosphodiester(PDE)/PCr and total
      Adenosine triphosphate(ATP) tend to decrease and the ratio of PDE/PME tend to
      elevate compared with controls. Moreover these findings are correlated with the
      duration of illness. Our results suggest that neural elements in basal ganglia
      may be damaged in PD. In conclusion, 31P-MRS appears to be useful for the study
      of neural damage and degeneration in vivo.

PMID- 9014461
TI  - [The role of magnetic resonance spectroscopic imaging in patients with
      Parkinson's disease].
AB  - There are some single voxel proton magnetic resonance spectroscopy(MRS) of
      Parkinson's disease but no multi-voxel proton MRS. Proton magnetic resonance
      spectroscopic imaging(MRSI) is the multi-voxel method, from which we can obtain
      many spectra from many voxel at the same time. The distribution of each
      metabolite can be observed in the metabolite map. Although defects in oxidative
      phosphorylation have been reported from the studies of Parkinson's disease and
      dopaminergic cell death has been observed, the cause of Parkinson's disease is
      unknown. The spectra from the striatum and surroundings and the metabolite maps
      in MRSI will help to understand the pathogenesis of the disease.

PMID- 9014462
TI  - [Correlation between MR imaging and histopathological findings of cystic
      metastatic brain tumors].
AB  - To clarify the correlation between the histopathological findings and MR signal
      intensity of the cyst wall, fifteen cystic metastatic brain tumors of eleven
      patients were imaged using a 0.5T MR unit just before surgery, and the MRI
      findings were correlated with the histopathological findings of resected lesions.
      On T2-weighted images, all cyst walls showed hypointensity. On T1-weighted
      images, the intensity of the cyst wall could be classified into three groups,
      compared with the cerebral cortex. Walls with hyperintensity on T1WI(group H; n =
      6) consisted of ample tumor cells, blood vessels and connective tissues,
      suggesting viable tumor cells. Iso-intense walls on T1W1(group I; n = 3)had
      abundant reactive glial tissues. Hypointense walls on T1W1 (group L; n =
      5)revealed hemorrhage and/or hemosicerin in the wall, suggesting hemorrhagic
      necrosis. Thus a good correlation was demonstrated between the MR signal
      intensities and histopathological findings of cyst walls of cystic metastatic
      brain tumors. This may contribute not only to more precise diagnosis on MRI but
      also to more planning for treatment of cystic brain metastases.

PMID- 9014463
TI  - [Evaluation of thin section CT scanning in the prone position of metastatic
      axillary lymph nodes for breast cancer].
AB  - A retrospective study was performed to determine whether thin section CT scanning
      in the prone position of the breast and the axilla yielded useful information
      regarding the status of axillary lymph nodes in patients with breast cancer.
      Thirty-six patients with breast carcinomas were scanned preoperatively from the
      supraclavicular regions to the breast in the prone position with 5 mm sections.
      Axillary lymph nodes measuring > or = 5 mm on the short axis were considered
      abnormal. Correlation with axillary dissection was obtained in all patients,
      giving a positive predictive value for axillary metastases of 83.3%, with 88.2%
      sensitivity, 84.2% specificity, and 88.8% negative predictive value. We concluded
      that thin section CT scan in the prone position was an accurate predictor of
      axillary lymph node involvement. We made a phantom with lymph node swelling to
      evaluate whether CT scanning with 5 mm sections was necessary for detecting 5 mm
      swollen lymph nodes. We scanned the phantom with 5 mm and 10 mm sections. Twelve
      radiologists counted the swollen lymph nodes on 5 mm section images and 10 mm
      section images of the phantom. The average number of miscounts was 1.1 (miscount
      rate 6.8%) on 5 mm section and 2.8 (15%) on 10 mm sections. We concluded that 5
      mm section CT scanning is superior for detecting 5 mm lymph nodes.

PMID- 9014464
TI  - [CT of metastatic pulmonary tumor: morphology, HRCT and histological
      correlation].
AB  - The purpose of this study was to evaluate the CT characteristics of metastatic
      pulmonary tumor. The study included 163 cases. Analysis of the distribution of
      1265 metastatic nodules observed the conventional and helical CT with 10 mm slice
      thickness showed that they were distributed mainly below the carina and external
      peripheral lung field. The relationship between the characteristics of the
      margins of the metastatic nodules and primary tumors was evaluated in 280 nodules
      with high-resolution CT(HRCT). The margins were smooth in 88% of thyroid cancers,
      85% of hepatocellular carcinomas and 75% of renal cell carcinomas, and irregular
      in 75% of pharyngolaryngeal cancers, 62% of colon cancers and 58% of breast
      cancers. HRCT findings were correlated with histology in 23 surgically resected
      metastatic nodules. The well-defined smooth margin on HRCT histologically
      corresponded to the expanding type, while the irregular margin corresponded
      predominantly to the alveolar space-filling type. Among other CT findings
      calcification was seen in colon cancer and osteosarcoma, and cavitation in
      pharyngolaryngeal cancer, colon cancer angiosarcoma, pancreatic cancer and
      endometrial uterine cancer. The author concludes that CT is useful for observing
      the morphologic features of metastatic pulmonary nodules which seem to reflect
      the underlying pathologic characteristics and thus contributes to the diagnosis.

PMID- 9014465
TI  - [Helical CT for lung-cancer screening: fourth report. Detectability of pulmonary
      lesions].
AB  - The detectability of various abnormal findings in helical screening CT(HSCT) with
      low-dose and single-breath-hold scanning of the lung was examined using
      conventional CT as a gold standard. In 75 patients, HSCT was obtained with
      scanning parameters of 120kVp, 50 mA, 10 mm-collimation. 20 mm/second and 1
      sec/rotation. Conventional CT was obtained with 150 mA and 10 mm-slice contiguous
      scanning HSCT depicted 141 of 159 focal lesions in nodules and masses (65 of 69
      lesions more than 5mm in size), 44 of 47 in infiltrative lesions, 11 of 11 in
      reticular lesions and 23 of 39 in bullae and blebs. There were only 3 false
      positive lesions in nodule and mass. Sensitivity, specificity and accuracy of
      HSCT for diffuse lesions were 100% (11/11), 95% (61/64) and 96% (72/75) for
      fibrotic change and 75% (9/12), 100% (63/63) and 96% (72/75) for emphysematous
      change, respectively. Since the detectability of HSCT was good for abnormal
      findings, showing increased attenuation in comparison with the lung parenchyma,
      it was considered to be a promising method for lung-cancer screening.

PMID- 9014466
TI  - [Clinical utility of MR FLAIR imaging for head injuries].
AB  - To study the utility of fluid attenuated inversion recovery (FLAIR)MR images in
      the evaluation of traumatic head injury, 56 patients with traumatic head injuries
      were examined with long TR/TE spin-echo(SE)sequences and FLAIR sequences. In 40
      of them, long TR/short TE images were added to those sequences. Careful readings
      of MR images were done by two well-trained neuroradiologists. The chi square test
      was used for statistical evaluation of our results. The relative sensitivities of
      FLAIR images were significantly better than those of long TR/TE, long TR/short TE
      images for the detection of diffuse axonal injury (p < 0.01), cortical contusion
      (p < 0.01), and subdural hematoma (p < 0.01) for long TR/TE, p < 0.05 for long
      TR/short TE). The number of cases of epidural hematoma and brainstem injury was
      too small for statistical significance to be determined. In 9 patients with
      corpus callosum injuries. FLAIR images demonstrated the lesions as abnormally
      high signal intensity in the septum pellucidum and fornix. Only sagittal FLAIR
      images could definitely discriminate the traumatic lesions of the fornix from the
      surrounding CSF. In addition, FLAIR images could easily discriminate DAI of the
      corpus callosum from CSF of the cavum velli interpositi. MR FLAIR images were
      found to be useful for detecting traumatic head injuries.

PMID- 9014467
TI  - [Prognostic factors of nasopharyngeal carcinoma treated by radiotherapy].
AB  - This study was a retrospective analysis of 82 patients with histologically
      confirmed nasopharyngeal carcinoma, who were treated at Keio University Hospital
      from March 1983 to March 1993. We studied all cases(62% of them were stage IV)
      with regard to their prognostic factors and chronic side effects induced by
      radiation. All patients were received extended-field radiotherapy from the base
      of the skull to the supraclavicular lymph node area. The five- and ten-year
      overall survival rates for the entire group were 59% and 49%, respectively. Three
      stage I patients were alive without recurrence or metastases for more than 5
      years. The ten-year survival rate stage II-III for patients (23 patients) was
      78%, and for stage IV (56 patients) 37%. The five-year survival rate of patients
      in T2-3 group without lymph node metastasis was 88%, while it was reduced to 55%
      for patients with metastasis. The prognosis of T4 patients was very poor: their
      five-year survival rate was 37% with lymph node metastasis, and 35%, without
      lymph node metastasis. Patients under 46 years old showed an increased survival
      rate compared with patients over 46 years old. Patients who completed less than
      52 days of radiation therapy found to have a better prognosis than those
      receiving radiation for a longer period. Our multivariate analysis indicated that
      age, radiation period and N-factor were statistically significant in influencing
      prognosis. Hearing loss occurred relatively high with 20% of cumulative incidence
      in our study, probably because they received radiation therapy with the extended
      field including bilateral middle and inner ear. Extended-field radiotherapy for
      patients with nasopharyngeal carcinoma might contribute to improving their cure
      rate, and precise radiation planning is warranted to avoid the late complications
      such as hearing loss.

PMID- 9014468
TI  - [Palliative radiation therapy for multiple myeloma].
AB  - PURPOSE: Radiation therapy is a useful palliative modality for refractory lesions
      of multiple myeloma. It has been reported that total doses of 10 to 20 Gy are
      usually adequate to obtain some degree of pain relief. However, there are many
      patients who need additional doses to obtain sufficient pain relief. In this
      study, we retrospectively analyzed the records of patients with multiple myeloma
      irradiated at our department, in an attempt to develop an effective treatment
      policy for this disease. MATERIALS AND METHODS: Twenty-nine patients with 53
      lesions were treated between 1968 and 1993. Total irradiation doses were 4 to 60
      Gy(median 40 Gy) with daily fractions of 2 Gy or less, and 16 to 51 Gy(median 30
      Gy) with daily fractions greater than 2 Gy. Evaluated were 59 symptoms, including
      pain (68%), neurological abnormalities (15%), and masses (28%). RESULTS:
      Symptomatic remission was obtained in 33 of 36 (92%) lesions with pain, 6 of
      8(75%) with neurological abnormalities, and 13 of 15(87%) mass lesions. Pain was
      partially relieved at a median TDF of 34, and completely at a median TDF of
      66(equivalent to 40-42 Gy with daily fractions of 2 Gy). CONCLUSIONS: Radiation
      therapy is an effective and palliative treatment method for symptomatic multiple
      myeloma. However, the treatment seems to require higher radiation doses than
      those reported to obtain adequate relief of symptoms.

PMID- 9014469
TI  - [Performance study of teleradiology network systems with CRT monitors: ROC
      analysis of an observation study of simulated lung nodules].
AB  - PURPOSE: To evaluate the diagnostic performance of commercially available CRT
      monitors used in a teleradiology system by determining the rate of detection of
      simulated lung nodules. MATERIALS AND METHODS: Three types of CRT monitors were
      tested in the observation study. They had matrix sizes of 1024 x 768(16 inches,
      color), 1024 x 768(20 inches, color) and 1600 x 1125(24 inches, black and white).
      Twenty chest radiographs were obtained by Fuji computed radiography(FCR) of an
      anthropomorphic chest phantom with ten simulated nodules on its surface. These
      FCR films were digitized by a film digitizer with 125 DPI(1024 x 1024 matrix
      sizes)and 12 bit gray scales, and the image data were transferred from Shinshu
      University Hospital to other hospitals where interpretation was carried out by
      the radiologists. Ten radiologists of three hospitals were asked to interpret
      independently both the original FCR films and the images shown on the CRT
      monitors and to indicate the presence or absence of simulated nodules on the
      images by using a five-category rating scale. Receiver operating
      characteristics(ROC)curves were generated, and the results of interpretation on
      the FCR films and CRT monitors were compared. RESULTS: Performance of the all
      readers was slightly better with the CRT monitors than on the FCR films, although
      the differences were not statistically significant. There were no statistically
      significant differences in performance depending on the type of CRT monitor.
      CONCLUSION: Performance of the CRT monitors was comparable to that of FCR
      radiography in terms of interpreting the simulated lung nodules.

PMID- 9014470
TI  - The radiosensitizing effects of hypoxic cell sensitizer on SCCVII tumors in mice
      evaluated by highly accurate colony formation assay assisted by microcomputer.

PMID- 9014471
TI  - [A case of malignant esophageal stenosis with esophagobronchial fistula treated
      with a covered wallstent].
AB  - A polyurethane-covered Wallstent was used for a esophagus cancer patient with
      malignant esophageal stenosis associated with esophagobronchial fistula. Stent
      placement was successfully performed with no procedure related-complications.
      Following the procedure the patient could eat a normal diet. The insertion of a
      polyurethane-covered Wallstent is a safe and effective treatment for malignant
      esophageal stenosis with esophagobronchial fistula.

PMID- 9014472
TI  - [Study of peritoneal water channel expression in rats].
AB  - Removal of excess fluid from patients with chronic renal failure is one of the
      major objectives of peritoneal dialysis (PD). Water movement from capillary to
      dialysate derives from the dialysate-to-capillary osmotic gradient across the
      peritoneum. To explain the mechanism of water movement driven by the osmotic
      gradient through the peritoneum, the notion of a water selective "ultra small
      pore" has been proposed. The purpose of this study was to investigate the
      involvement of peritoneal water channels in water movement across the peritoneum
      in PD. The abdominal cavity of male anesthetized rats was catheterized for
      administration of a series of artificial dialysates. Experimental PD was
      performed for 90-180 min with 25 ml of hyperosmotic dialysate generated by
      glucose (600 mOsm), sucrose (600 mOsm), and sodium (1800 mg/dl, 600 mOsm).
      Analysis of the sodium concentration and osmolality of dialysate during
      experimental PD showed mercurial sensitive water transport that was compatible
      with water channel-mediated water transport in the peritoneum. RT-PCR
      amplification with cDNAs constructed from peritoneal mRNA revealed the existence
      of both AQP1 (CHIP28) and AQP4 (MIWC) water channels in the peritoneum. PD with
      hyperosmotic dialysate did not affect the expression of peritoneal water
      channels. As a result of an in situ hybridization study to investigate the
      localization of the peritoneal water channels, it was found that both channels
      were expressed in the sub-mesothelial layer containing capillaries. The results
      obtained in this study suggest that peritoneal water channels might play a role
      in fluid removal during PD.

PMID- 9014474
TI  - [Age-related changes in morphological studies in rat and human kidney].
AB  - There have been many reports on changes in renal morphology with aging. In this
      study, morphological comparisons were made on the influence of aging in humans
      and rats. Kidneys were obtained from 63 autopsies (except those from cases of
      tumor, severe cicatrization, and cysts 10 mm or more in diameter) performed on
      humans aged from 0 to 92 years, including 7 cases with a past history of
      hypertension; the findings were compared with those from 201 Wistar male rats
      aged three to 115 weeks. First, changes in renal weight and renal cortex width
      were investigated. Next, changes in renal morphology were examined by microscopy.
      Finally, after performing alcian-blue-PAS staining, the ratio of the intima/outer
      diameter (I/OD ratio) of renal blood vessel was measured under a microscope with
      an image analyzer, and the results compared. A decrease in renal weight was
      observed in humans from about 50 years of age, but there was no decrease in
      weight with aging among rats. While significant thickening in the vascular intima
      was observed with aging in humans, there was no such thickening among rats.
      Furthermore, the presence of hypertension caused renal cortex width to be
      significantly decreased in humans (p < 0.04). Findings of sclerogenous changes of
      the glomeruli, infiltration of chronic inflammatory cells and fibrosis in the
      stroma, and tubular casts were observed with aging in both humans and rats. In
      conclusion, arteriosclerosis apparently develops with aging in humans, suggesting
      that arteriosclerosis greatly influences the reduction of human renal weight.

PMID- 9014473
TI  - [Expression of FGF2, FGF receptor-1 and alpha-smooth muscle actin in experimental
      mesangial proliferative nephritis].
AB  - Mesangial cell (MC) proliferation is the principal cause of glomerulonephritis
      and glomerulosclerosis. Previous studies have demonstrated that various cytokines
      and growth factors are MC mitogens. In vitro, basic fibroblast growth factor
      (FGF2) stimulates MC proliferation. In the present study, two series of
      experiments were conducted using rats with anti-Thy 1.1 mesangial proliferative
      glomerulonephritis. The first series of experiments was designed to clarify the
      expression relationship between FGF2, FGF, receptor-1 (FGFR1) and alpha-smooth
      muscle actin (alpha-SMA). The second series examined the effect of intravenous
      administration of recombinant FGF2 in this model. The first series involving in
      situ hybridization with FGF2 and FGFR1 cRNA probes, showed that these mRNAs were
      expressed in the mesangial areas during the proliferative phase (days 4-7).
      Simultaneously, the alpha SMA scores of glomeruli also increased. In the second
      series, FGF2 was administered at 6, 12 and 24 hours (early group) and at 4, 5,
      and 6 days (late group) after disease induction. On day 7, there were more
      glomerular cells positive for proliferative cell nuclear antigen (PCNA) in the
      late group than in the control and early groups and the alpha-SMA scores of the
      glomeruli had increased in the late group. On day 14, the number of mesangial
      cells mainly increased in the late group. These findings suggest that FGF2 and
      FGFR1 showed significant correlation with the phenotypic changes of MC.

PMID- 9014475
TI  - [Effects of neutralizing antibodies on cytokine treatment for anti-GBM nephritis
      in mouse].
AB  - The process of glomerular injury in nephrotoxic serum nephritis (NTN) is
      dependent on proinflammatory cytokines. In the present investigation, we assessed
      the actions of neutralizing antibody against IL-1 beta, TNF-alpha, IL-6 and TGF
      beta 1 on glomerular injury. Marked increase in IL-1 beta and IL-6 was detected
      in cultured glomeruli of NTN in mice throughout the experiments from disease
      induction. Protein of TNF-alpha and TGF-beta 1 also increased in NTN mice 1 day
      after disease induction. Treatment with either IL-1 beta or TNF-alpha
      neutralizing antibody reduced proteinuria from 71 +/- 11.2 m g/24 hr to 32.2 +/-
      6.0 (P < 0.01). 34.3 +/- 6.8 mg/24 hr (P < 0.01), respectively. Although the
      effect of IL-6 neutralizing antibody on proteinuria was not remarkable, the
      decreased creatinine clearance was improved more than that of IL-1 beta or TNF
      alpha. Antibody against TGF-beta 1 had no effect on proteinuria and creatinine
      clearance. Treatments with IL-1 beta, TNF-alpha and IL-6 neutralizing antibodies
      inhibited glomerular hypercellularity in NTN mice. TGF-beta 1 neutralizing
      antibody suppressed the index of mesangial matrix expansion. IL-1 beta and TNF
      alpha neutralizing antibodies prevented the increase in the number of macrophages
      in the glomeruli. The number of PCNA positive cells and alpha-smooth muscle actin
      expression in glomeruli was significantly reduced in the IL-6 neutralizing
      antibody-treated group. These results confirm the direct involvement of IL-1
      beta, TNF-alpha and IL-6 in mouse NTN. We speculate that TGF-beta 1 may inhibit
      excessive proliferation in glomerular cells.

PMID- 9014476
TI  - [Role of intercellular adhesion molecule (ICAM)-1 in the interaction between
      glomerular endothelial cells and granulocytes].
AB  - The present study was designed to investigate the role of intercellular adhesion
      molecule (ICAM)-1 in the interaction between glomerular endothelial cells (GEN)
      and granulocytes. Expression of ICAM-1 was promoted after stimulation with tumor
      necrosis factor (TNF)-alpha. This effect was dose- and time-dependent.
      Granulocytes attached to GEN in accordance with the increased expression of ICAM
      1 on the cells stimulated with TNF-alpha. In addition, the adhesion of
      granulocytes to activated GEN with TNF-alpha stimulated specific [51Cr] release
      from the monolayers. Furthermore, monoclonal antibodies to TNF-alpha dose
      dependently inhibited the adhesion of granulocytes to activated GEN. In summary,
      ICAM-1 is related to the glomerular endothelial cell injury induced by
      granulocytes activated with TNF-alpha, suggesting that ICAM-1 may play a role in
      the initiation of certain types of glomerulonephritis with granulocyte
      infiltration.

PMID- 9014477
TI  - [The role of xanthine dehydrogenase (xanthine oxidase) in ischemia-reperfusion
      injury in rat kidney].
AB  - Xanthine dehydrogenase (XDH) and xanthine oxidase (XO) are enzymes involved in
      the metabolism of purines in various organisms. XO produces superoxide radicals,
      suggesting that is responsible for tissue ischemia-reperfusion injury. To test
      this notion further studies were performed on rat kidneys and the time course of
      changes in purine nucleotides, oxypurines and XDH and XO activity was determined.
      At 24 hours after reperfusion subsequent to 30-minute ischemia, serum creatinine
      increased to 0.83 +/- 0.74 mg/dl from 0.28 +/- 0.06 mg/dl (the level prior to
      ischemia, the control). Renal ATP and ADP contents were reduced after ischemia
      lasting for 30 minutes and restored 10 minutes after reperfusion following 30
      minutes of ischemia. The renal AMP content increased after 30 minutes of ischemia
      and recovered within 10 minutes after reperfusion. The total adenine nucleotide
      (TAN) content was reduced gradually during ischemia-reperfusion in the rat
      kidney. Although the energy charge was reduced following 30 minutes of ischemia,
      it was restored to the control level 10 minutes following reperfusion.
      Hypoxanthine (HX) and xanthine (X), which had accumulated at 30 minutes after
      ischemia, were reduced to the control levels 10 minutes after reperfusion. There
      were no significant changes in the pre-ischemia values of total XDH and XO
      activities or XDH/XO ratio during the period nor at various time intervals (up to
      24 hours) during reperfusion. It was shown that HX and X accumulate without
      significant conversion of XDH to XO during ischemia. Therefore the putative role
      of XO in ischemia-reperfusion injury seems to more complex than initially
      predicted.

PMID- 9014479
TI  - [A study on angiotensin-I converting enzyme polymorphism in CAPD patients].
AB  - To clarify the role of genes related to angiotensin-I converting enzyme (ACE),
      the author investigated polymorphism of the ACE gene in 60 patients undergoing
      chronic ambulatory peritoneal dialysis (CAPD) and 50 patients undergoing
      hemodialysis (HD). One hundred healthy subjects were used as controls. The
      polymorphism was classified into three genotypes, II, ID and DD, according to
      insertion (I) and deletion (D) using the polymerase chain reaction method. In
      dialysis patients (CAPD or HD, n = 110), 21.8% had the II genotype, 48.2% the ID
      genotype, and 30.0% the DD genotype. There was a significant difference in allele
      frequency between normal subjects (n = 100) (J = 0.63, D = 0.37) and dialysis
      patients (I = 0.46, D = 0.54) (chi 2 = 12.321, p < 0.001). The mean plasma ACE
      activity was 9.9 +/- 1.6 IU/l in CAPD patients with the II genotype, 11.6 +/- 4.7
      IU/l in CAPD patients with the ID genotype, and 14.5 +/- 3.5 IU/l in CAPD
      patients with the DD genotype. The mean rate of decrease in residual urinary
      volume was 0.8 +/- 0.7% per month in CAPD patients with the II genotype 1.4 +/-
      1.3% per month in CAPD patients with the ID genotype, and 2.5 +/- 2.0% per month
      in CAPD patients with the DD genotype. These data showed a significant decrease
      in urinary volume in CAPD patients with the DD genotype (p < 0.05). The mean rate
      of decrease in residual urinary volume was positively correlated with the plasma
      ACE activity (r = 0.13389, p < 0.02). In CAPD patients, the mean cardiothoracic
      ratio was 46.6 +/- 3.5% in cases with the II genotype, 47.6 +/- 5.5% in cases
      with the ID genotype, and 52.9 +/- 8.4% in cases with the DD genotype. These data
      indicated significant cardiac enlargement in DD genotype cases. It can be
      concluded that CAPD patients with the DD genotype lost their residual renal
      function more rapidly and had a larger heart, than patients with the other
      genotypes.

PMID- 9014478
TI  - [Impaired neutrophil function in chronic renal failure--dysregulation of surface
      adhesion molecule expression and phagocytosis].
AB  - To elucidate the impaired neutrophil function in patients with chronic renal
      failure, we analyzed the expression of the adhesion molecules, LAM-1, LFA-1, Mac
      1, gp150/95 and phagocytosis activity of neutrophils in predialysis and
      hemodialysis patients by flow cytometry. Further, the response to granulocyte
      colony-stimulating factor (G-CSF), N-formyl-methionyl-leucyl-phenylalanine (fMLP)
      and tumor necrosis factor alpha (TNF alpha) were investigated. In hemodialysis
      patients, the expression of LAM-1 was decreased and that of MAC-1 was increased,
      indicating the activation of neutrophils. Also in predialysis patients, the same
      condition of "low LAM-1, high MAC-1" was observed, but to a lesser degree.
      Phagocytosis activity was significantly decreased in hemodialysis patients,
      whereas the neutrophils of predialysis patients showed almost the same
      phagocytosis activity compared to the controls. The responses to G-CSF, fMLP, TNF
      alpha were significantly reduced both in hemodialysis and predialysis patients.
      The inadequate activation of neutrophils and impaired response to stimulation may
      play an important role in uremic patients with regard to increased susceptibility
      to infections.

PMID- 9014480
TI  - [Membranous nephropathy in Japanese children].
AB  - Since 1973, 15 patients, consisting of 8 boys and 7 girls, were diagnosed as
      having membranous nephropathy (MN). The average age at detection was 8.2 years (2
      14 years). The presenting symptom was edema in 1, pyrexia in 1 and upper
      respiratory infection in 1 case, in the all other cases, abnormal urinalysis was
      detected by the school or chance urinalysis. Surface antigen of hepatitis B virus
      (HBs) was positive in 6 patients and negative in 9. Anti-nuclear antibody (ANA)
      was positive in 3 and negative in 11. In one patient, ANA was not tested. One
      patient who was negative for ANA was diagnosed as having SLE 4 years later. At
      the last follow-up, 10 patients continued to have urinary abnormalities. Among
      these was one case positive for HBs antigen who went into end-stage renal
      failure. In the other 14 patients, the serum creatinine level was below 1.4
      mg/dl. All patients showed a normal mesangium or mild mesangial proliferation.
      The patient diagnosed as having SLE. 4 years later showed mesangial deposits at
      the first renal biopsy. In our experience, most patients with MN were detected by
      the school or chance urinalysis and six of the these had positive HBs antigen.
      Lupus nephritis must be ruled out in making a diagnosis of idiopathic MN.

PMID- 9014481
TI  - [Effect of histamine H2-receptor antagonists on the phosphorus-binding ability of
      phosphate binders in hemodialysis patients].
AB  - We examined the effects of histamine H2-receptor antagonists on the phosphorus
      binding ability of phosphate binders. Serum calcium, phosphorus, ALP, PTH and
      arterial blood pH and bicarbonate were measured during treatment with histamine
      H2-receptor antagonists accompanied by calcium carbonate in sixteen patients
      undergoing maintenance hemodialysis. Seven patients receiving histamine H2
      receptor antagonists without calcium carbonate were selected as controls. In the
      sixteen patients receiving calcium carbonate, serum calcium, ALP, PTH and
      arterial blood pH and bicarbonate were not significantly altered during treatment
      with histamine H2-receptor antagonists, but serum phosphorus levels increased
      significantly after four (5.6 +/- 1.1 mg/dl) and eight weeks (5.9 +/- 0.8 mg/dl)
      of treatment as compared with that before treatment (4.8 +/- 1.2 mg/dl).
      Furthermore, serum phosphorus levels decreased significantly eight weeks after
      the discontinuation of treatment with histamine H2-receptor antagonists. In the
      seven control patients there were no statistical differences in serum calcium and
      phosphorus levels measured before and after treatment with histamine H2-receptor
      antagonists. In seven other patients receiving histamine H2-receptor antagonists
      with calcium carbonate, calcium carbonate was replaced with calcium lactate as
      the phosphate binder after four weeks of treatment with histamine H2-receptor
      antagonists. With the 4-week administration of histamine H2-receptor antagonists
      accompanied by calcium carbonate, the serum phosphorus level increased, similarly
      to that of the first study (from 6.3 +/- 0.9 to 7.1 +/- 0.5 mg/dl). However, with
      the substitution of calcium lactate, the serum phosphorus level decreased
      significantly (6.3 +/- 0.2 and 6.0 +/- 0.9 mg/dl after four and eight weeks,
      respectively, despite continued administration of histamine H2-receptor
      antagonists). These results suggest that histamine H2-receptor antagonists
      significantly affect the phosphorus binding ability of calcium carbonate, but not
      of calcium lactate. Although the exact mechanism remains obscure, one possible
      explanation may be related to the rise in pH of the gastric juice. Careful
      observation of changes in the serum phosphorus level is required in hemodialysis
      patients receiving calcium carbonate and histamine H2-receptor antagonists.
      Calcium lactate may be useful as a phosphate binder in such hemodialysis
      patients.

PMID- 9014482
TI  - [Evaluation of nutritional status of patients on continuous ambulatory peritoneal
      dialysis (CAPD) by dual photon energy X-ray absorptiometry (DEXA)].
AB  - Malnutrition is a serious complication in patients on long-term CAPD treatment.
      Accordingly, quantitative evaluation of nutritional status is a critical issue.
      This study aimed to assess nutritional status by dual photon energy x-ray
      absorptiometry (DEXA) in CAPD patients. Total lean body mass (D-TBM), right arm
      lean mass (D-RAM) and body fat percent (D-% FAT) measured by DEXA were compared
      with mid-arm muscle circumference (MAMC) and body fat percent (AP-% FAT) measured
      by anthropometrics (AP) in 51 CAPD patients. The subjects were stratified into
      groups by gender, age, duration on CAPD, and diabetes mellitus or non-diabetes.
      There was significant correlation between D-TBM, D-RAM and MAMC (r = 0.519, p =
      0.001, r = 0.545, p = 0.001) or D-% FAT and AP-% FAT (r = 0.763, p = 0.0001).
      However, in the groups of females with over 50 years and over 48 months of
      dialysis duration, there was no correlation between D-TBM, D-RAM and MAMC. The
      DEXA method is useful in the quantitative evaluation of nutritional status of
      dialysis patients serially.

PMID- 9014483
TI  - [Clinical effects of beni-koji in mild essential hypertension--a multi-center
      double-blind comparison with placebo].
AB  - Antihypertensive effects of beni-koji were studied using 29 outpatients with mild
      hypertension in a placebo-controlled double-blind comparative fashion. After a 4
      week vehicle (apple juice) run-in period, 13 patients were assigned to receive
      beni-koji aqueous extracts containing juice once daily (27 g of beni-koji eq. per
      day) for 8 weeks and 16 were assigned to vehicle. Two patients assigned to the
      vehicle group did not complete the study. In addition to casual blood pressure,
      24-hr non-invasive ambulatory blood pressure (ABP) was monitored in 6 patients
      given the beni-koji drink and 5 patients given the vehicle. 1) In the beni-koji
      group, both casual systolic and diastolic pressure decreased significantly during
      the treatment period (from 150 +/- 10/96 +/- 6 mmHg to 140 +/- 10/89 +/- 10 mmHg,
      p < 0.01). The averages of the 24-hr blood pressure recorded in ABP (24-BP) also
      significantly decreased (from 141 +/- 17/95 +/- 13 mmHg to 132 +/- 21/86 +/- 10
      mmHg, p < 0.05) when compared with those of the control period. Casual pressure
      normalized (less than 140/90 mmHg) in 4 patients who received beni-koji.
      Circadian variation of the blood pressure by ABP showed a significant decrease
      during the daytime. 2) In the vehicle group, casual systolic pressure did not
      change significantly (from 155 +/- 8 mmHg to 151 +/- 12 mmHg), but diastolic
      pressure decreased significantly (98 +/- 7 mmHg to 93 +/- 6 mmHg). Casual blood
      pressure did not normalize in any of the patients and 24-BP did not change
      significantly. 3) Summative evaluation of safety showed that no problems appeared
      in the beni-koji group. In conclusion, beni-koji appears to be an effective and
      safe food material for mild essential hypertension. The mechanism of the
      antihypertensive effect of beni-koji still remains to be investigated.

PMID- 9014484
TI  - [Acute effects of human recombinant erythropoietin on cardiovascular dynamics and
      vasoactive substances].
AB  - Treatment with human recombinant erythropoietin (r-EPO) can dramatically improve
      renal anemia, whereas it has been reported that such improved anemia may involve
      or worsen hypertension. When we administered a single dose of r-EPO at 9,000
      units to 16 patients with end-stage renal failure requiring examination with a
      right cardiac catheter immediately before the introduction of dialysis, we
      measured cardiovascular dynamics and various vasoactive substances. The mean
      blood concentration of EPO was 3,035 units/ml 15 minutes after administration. As
      compared with the value of 107.6 +/- 3.2 mmHg obtained before administration, the
      mean arterial blood pressure significantly increased following the administration
      of r-EPO to 111.5 +/- 3.8 mmHg after 5 minutes, 112.4 +/- 4.2 mmHg after 10
      minutes, 113.7 +/- 4.3 mmHg after 20 minutes, and 113.6 +/- 4.3 mmHg after 30
      minutes (p < 0.05). The mean pulmonary arterial blood pressure tended to increase
      to 17.9 +/- 1.8 mmHg after 10 minutes from the level of 16.3 +/- 1.8 mmHg before
      administration (p = 0.096). The pulmonary vascular resistance index (PVRI) was
      165.0 +/- 18.0 mmHg before administration and significantly increased to 193.2 +/
      19.0 and 199.0 +/- 16.6 dyn.S.cm-5.m2 after 10 and 30 minutes, respectively (p <
      0.01, p < 0.05). The systemic vascular resistance index (SVRI) also significantly
      increased to 2,587 +/- 195 dyn.S.cm-5.m2 after 30 minutes from the level of 2,454
      +/- 207 dyn.S.cm-5.m2 before administration (p < 0.05). Changes in SVRI showed a
      bimodal pattern, as with changes in PVRI. Angiotensin-II concentration
      significantly decreased to 13.7 +/- 4.4 pg/ml after 15 minutes from the level of
      15.7 +/- 3.2 pg/ml before administration (p < 0.05). There were no significant
      changes in endothelin, prostaglandin, or adrenaline concentration after the
      administration of r-EPO. From these results, it was revealed that pulmonary intra
      arterial administration of r-EPO has the acute effect of increasing pulmonary
      vascular resistance, thereby pointing to a direct effect of r-EPO in pulmonary
      vasoconstriction. Although no changes in vasoactive substances were observed in
      the present investigation, further studies with more sensitive measuring methods
      may be necessary.

PMID- 9014485
TI  - [A study of serum oxipurinol concentration and renal function in patients
      administered allopurinol].
AB  - Allopurinol is used frequently to treat patients with gout and hyperuricemia.
      However, adverse effects associated with this agent have been reported
      occasionally, especially among patients with hyperuricemia complicated with renal
      diseases. A rise in the blood concentration of oxipurinol, the chief active
      metabolite of allopurinol, has been noted in patients with renal dysfunctions,
      pointing to an implication of oxipurinol toxicity. It has been reported that
      monitoring the serum oxipurinol concentration to maintain in level below 15.2
      micrograms/ml (= 100 mumol/l: recommended level) is helpful in avoiding toxicity.
      At Jikei University Hospital, a survey was conducted on 148 hyperuricemic
      patients who had been treated with allopurinol at the dosages of 50, 100, 200 and
      300 mg daily or 100 mg on alternate days for more than one month. Because
      oxipurinol is an uricosuric substance, the steady-state serum oxipurinol
      concentration was determined by HPLC; and creatinine clearance (CCr) was
      calculated for each patient. 1. In the group composed of patients with normal
      kidney function (CCr > or = 80 ml/min), increase in the dosage of allopurinol was
      associated with a linear increase in the serum concentration of oxipurinol. 2.
      Among the patients with varying renal function who were receiving 100 mg of
      allopurinol daily, the oxipurinol level increased logarithmically as the
      creatinine clearance decreased. In some of the patients with renal insufficiency
      (CCr < 30 ml/min), daily administration of 100 mg of allopurinol resulted in a
      serum concentration of oxipurinol over 15.2 micrograms/ml. 3. For patients with
      renal insufficiency (CCr < 30 ml/min), administration of allopurinol at the
      dosage of 50 mg/day is considered adequate to avoid the accumulation of serum
      oxipurinol.

PMID- 9014486
TI  - Computer-based medical records: the next wave.
AB  - Computer-based records systems for practice management are commonplace, but
      computer-based systems for monitoring patient care are not, and for good reason:
      Recording useful clinical information is far more complex than scheduling
      appointments and submitting bills. Even so, a lot of people are making progress
      toward computer-based medical records. Here are some of the issues involved.

PMID- 9014487
TI  - The employer's bird's-eye view.
AB  - Managed care has become a viable alternative for employers nationwide, Pittsburgh
      employers explain why.

PMID- 9014488
TI  - Drug education. Moving ahead the fourth year.
AB  - The Omnibus Budget Reconciliation Act (OBRA) of 1990 required all states to
      implement drug utilization review programs for outpatient medications covered by
      Medical Assistance. This second of a two-part series outlining the activities of
      the State Society's Center for Professional Drug Education and Information
      discusses the effectiveness of Pennsylvania's program.

PMID- 9014489
TI  - [Matrix metalloproteinases: their structures and functions, with special
      reference to their roles in tumor invasion and metastasis].

PMID- 9014490
TI  - [Mechanism of the induction of apoptosis in cancer cells].

PMID- 9014491
TI  - [Biochemical mechanisms of the DNA cleavage induced by NCS-chromophore].

PMID- 9014492
TI  - [MAP kinase cascade regulating TGF beta signaling pathway].

PMID- 9014493
TI  - [HMG box proteins: general architectural elements in the assembly of active
      transcription complex].

PMID- 9014494
TI  - Latest eruptions in metabotropic glutamate receptors.

PMID- 9014495
TI  - Peptide YY and neuropeptide Y: two peptides intimately involved in electrolyte
      homeostasis.

PMID- 9014496
TI  - Resolution of chronic inflammation by therapeutic induction of apoptosis.

PMID- 9014497
TI  - Quantitation of allosteric interactions.

PMID- 9014498
TI  - Amphotericin B: new life for an old drug.
AB  - Interest in amphotericin B has undergone a renaissance of sorts over the past few
      years despite the advent of the newer less-toxic azole antifungal drugs. This is,
      in part, owing to the unfortunate increase in fungal diseases worldwide. It is
      also, however, owing to the reduction of toxicity via innovative liposomal
      delivery systems, better understanding of drug mechanism and distribution and a
      surprising expansion of the antibiotic spectrum of amphotericin B to include
      select virus, parasite and possibly prion infections. In this article, Scott
      Hartsel and Jacques Bolard summarize the recent leaps in pharmaceutics, spectrum
      and molecular mechanistic knowledge of this surprising molecule.

PMID- 9014499
TI  - Recombinant proteins for therapy.
AB  - Recombinant therapeutic proteins have become increasingly important over the past
      ten years. Numerous products derived from 20 different proteins are already on
      the market. In this review Peter Buckel discusses the issues surrounding the use
      of recombinant proteins as therapeutic agents. The first generation proteins for
      therapy all occur naturally in humans. Protein engineering has brought forth a
      second generation of products with application-specific properties obtained by
      fusion, mutation or deletion. The third generation of therapeutic proteins is
      produced by patients themselves after transfer of the relevant genes. The first
      successful applications of this gene therapy represent a new milestone in
      medicine.

PMID- 9014500
TI  - GABA and its receptors in the spinal cord.
AB  - The importance of the inhibitory neurotransmitter, GABA, within higher centres of
      the mammalian brain is unquestionable. However, its role within the spinal cord
      is of equal significance. There have been numerous studies over the past two
      decades that have established GABA as a neurotransmitter at both post- and
      presynaptic sites in the cord. Here, Marzia Malcangio and Norman Bowery review
      the current status of GABA in relation to nociception and skeletal muscle tone,
      and indicate that its contribution to spinal cord function should not be
      overlooked.

PMID- 9014501
TI  - The future of radiology in west Africa.

PMID- 9014503
TI  - Day surgery at Korle Bu Teaching Hospital: a six year review.
AB  - Day surgery is not simply a matter of economics for the health institution or the
      individual patient, or improved utilization of scarce and dwindling resources, or
      even a matter of increasing access to health care, fundamental as this is to us
      in the developing world. The ultimate question is to what extent does it satisfy
      the true needs of the patient and meet the requirements of his care as a whole.
      To address this day surgery in a general surgical unit has been reviewed over a 6
      year period. This covered a total of 1547 cases consisting of hernias,
      hydroceles, excision biopsies, varicose veins etc. Infiltrative local anaesthesia
      using lignocaine (4 mg/kg) mostly with 1 in 200,000 adrenaline added proved
      effective in 98 percent of cases; there were no deaths. For the institutions day
      surgery has proven cost effective, lowering cost of operative treatment and
      improving utilization of scarce resources. It has also proven eminently
      acceptable to patients and their families, enhancing access to care and
      significantly reducing the personal cost of treatment. To demonstrate enhanced
      health economics future studies should ideally show a parallel diminution of in
      patient bed facilities with increasing load of day surgery.

PMID- 9014502
TI  - Limb salvage in peripheral vascular trauma.

PMID- 9014504
TI  - Selecting paediatric surgical patients for day care surgery--a ten year
      experience (1980-1989) in the UNTH, Enugu, Nigeria.
AB  - Selecting the right paediatric surgical patients for Day care Surgery is an
      important part of ensuring that the quality of medical care is preserved in this
      setting. The exponential growth of out-patient Surgery of the 1980's in the
      developing countries is such that in the quinqennium starting from 1995, perhaps
      more that 65% of all elective Surgery can be performed on an out-patient basis.
      This communication examines what adaptations are necessary, particularly in
      preparative screening and patient selection, to meet the demands of Day Care
      (ambulatory) Surgery in paediatric Surgical patients in a tertiary hospital
      facility. A ten-year experience (January 1980-December 1989) in the University of
      Nigeria Teaching Hospital (UNTH), Enugu, Nigeria is the basis of our review.

PMID- 9014505
TI  - Socio-economic factors and dental health in an obstetric population.
AB  - The relationship between socio-economic factors and dental health in an Obstetric
      Nigerian population was studied. The mean gestational age (+/-standard deviation)
      was 30.16 + 5.45 weeks (range 16-40 weeks). Acquisition of dental education was
      found to be unrelated to level of education. When the prevalence of dental caries
      and periodontal disease were considered, the difference between the high, middle
      and low socio-economic groups were found to be significant (p < 0.05).

PMID- 9014506
TI  - Platelet counts in healthy adult Sierra Leoneans.
AB  - The platelet counts of 100 healthy Sierra Leoneans were determined. Fifty six
      (56) Males and Forty four (44) Females were included in the study. The mean
      platelet count was 197 x 10(9)/L(SD = 25 x 10(9)/L Range = 115-335 x 10(9)/L The
      results of this study compare favourably with those obtained from previous
      studies in other African Countries and confirms that the normal platelet count in
      the African is lower than in Caucasians.

PMID- 9014507
TI  - Multiple-resistant Salmonella group G outbreak in a neonatal intensive care unit.
AB  - An outbreak of nosocomial infection due to multiple-resistant Salmonella Group
      "G' infection in a neonatal intensive care unit in a temporary ward is reported.
      It started with five cases of Septicaemia and one case of meningitis over a
      period of about six weeks. Investigation of the outbreak resulted in isolation of
      a multiple-resistant Salmonella Group G from the rectal swab of 21 out of 72
      babies (29%). Surveillance culture from staff yielded two fully-sensitive
      salmonella species. Stool culture from mother of colonised babies were all
      negative. Environmental cultures from the nursery grew multiple-resistant
      Salmonella Group G from three of four incubator mattresses and also from the
      radiant warmer. Institution of strict aseptic measures, followed by closure of
      the ward was able to stop the epidemic.

PMID- 9014508
TI  - Age at menarche amongst school girls in a high altitude Nigerian town.
AB  - Menarche, the first menstrual period is believed to be influenced by many factors
      including altitude. The data of 331 school girls in Jos (1,300 m above sea
      level), a high altitude Nigerian town, that attained menarche between January
      1989 were analysed. The mean menarcheal age for these school girls is 13.21 +/-
      1.01 years. This value was not significantly different from 13.02 +/- 1.28 years
      found amongst school girls at Calabar (20 m above sea level) a Nigerian sea level
      resident sample. Perhaps, Jos is not situated at a high enough altitude to
      significantly affect the age at which menarche is attained.

PMID- 9014509
TI  - Upper urinary tract stones in Accra, Ghana.
AB  - Fifty-one patients with newly diagnosed upper urinary tract stones were seen at
      the Korle Bu Teaching Hospital, Accra over an 8 years period from September 1985
      to August 1993. Their mean age was 40.1 years (range 20-61 years). The sex ratio
      was 36 males to 15 males. During the same period 3, 217, 135 patients (both
      adults and children) attended the hospital's clinics. Thus putting the incidence
      of upper urinary tract stone at 2 per 100,000. On presentation 37 patients had
      solitary stones, 11 had multiple stone and 3 had partial or complete staghorn
      calculi. A total of 71 stones were seen; 30 were renal and 35 ureteric. The
      etiology of the stone disease was established in only 10 cases (20%). Urinary
      stasis was a predisposing factors in 5 patients, urinary infection in 3 others
      and hyperuricaemia and uricosuria in another 2. Stones from 29 patients that were
      removed at surgery or passed spontaneously were analysed chemically. Of these 25
      (86%) consisted of calcium oxalate and/or calcium phosphate, 3 (10%) consisted of
      magnesium ammonium phosphate and 1(4%) contained only uric acid.

PMID- 9014510
TI  - Premarital conception in married couples: the Nigerian Igbo experience.
AB  - Analysis of data from 142 married Nigerian Igbo primigravidae seen at the
      University of Nigeria Teaching Hospital, Enugu, from May 3, 1990 to August 31,
      1990 revealed an incidence of premarital conception of 65.5%. This group of women
      were younger and had more representation in the lower social classes when
      compared to those who only became pregnant after marriage. Both groups were
      similar in their mean heights, incidence of anaemia, maternal health during
      pregnancy and tended to book for antenatal care late in pregnancy. The reasons
      for this state of affairs were examined.

PMID- 9014511
TI  - Acute respiratory infections in young children comparative findings in emergency
      rooms in Accra, (Ghana) and Harare (Zimbabwe).
AB  - A descriptive study of the emergency room outcome of Acute Respiratory Infections
      (ARI) in children aged 0-3 years in the department of Child health of the Korle
      Bu Teaching Hospital (KBTH), Ghana and Parirenyatwa Hospital (PH), Zimbabwe was
      undertaken in June-July 1993. Each hospital's emergency room received over one
      thousand patients during the period with ARI contributing 22.4% to 45.5% of all
      admissions. KBTH had the lower incidence of ARI; probably as a result of the
      general lack of knowledge of ARI, resulting in late case of identification and
      referral for treatment. In PH, the colder environmental temperatures in
      June/July, the comprehensive ARI control programme and the HIV/AIDS and
      Tuberculosis epidemic could in part explain the relatively high attendance of
      patients with ARI to the emergency room. Our study shows an appreciable decline
      in the severer forms of ARI from the first to the third year of life, confirming
      the noted importance of younger age as a universal risk factor in ARI outcome.
      Lower respiratory infections, mainly pneumonia and bronchiolitis were more
      prevalent in both countries, while the chance of a child dying from ARI was
      higher in KBTH. Ghana urgently needs a comprehensive national ARI control
      programme based on the WHO case control programme guidelines with antibiotics
      permissible at all levels of the health service.

PMID- 9014512
TI  - Antitumor effect of pre-transplantation local hyperthermia and augmentation by
      dietary unsaturated fat.
AB  - Antitumor effects of pre-transplantation hyperthermia and its correlation to
      immunological changes in the host animals and enhancement by dietary unsaturated
      fat have been studied. Leg muscles of mice were locally heated (41 degrees-43
      degrees C, 40 min) and fibrosarcoma cells were inoculated into the heated and
      unheated sites and tumor growth time was determined. Spleen cell activity and
      plasma levels of interleukins (IL1 and 2) [RIA kits] were assessed. Muscle and
      tumor fatty acid profiles were modified by feeding mice with unsaturated fat
      supplemented diet and analysed by GLC. Pre-transplantation hyperthermia
      suppressed the tumor growth on both heated and unheated contralateral legs of
      mice. These effects were associated with increased spleen cell activity and
      plasma levels of IL1 and 2. Diet rich in unsaturated fat altered the fatty acid
      profiles of the leg muscles and tumors and inhibited tumor growth. It also
      potentiated the antitumor effect of pre-transplantation hyperthermia. In
      conclusion, mild local hyperthermia induces both direct and abscopal antitumor
      effects which may be ascribed to stimulation of host's antitumor immune responses
      and these effects are augmented by unsaturated fat supplemented diet.

PMID- 9014513
TI  - Simultaneous treatment of an experimental tumour with fractionated radiation and
      infrared-A-hyperthermia.
AB  - Experiments on rat rhabdomyosarcomas R1H were performed to evaluate the
      therapeutic potential of a simultaneous radiation-hyperthermia treatment of
      superficially growing tumours. Tumours were heated locally with infrared-A
      radiation and irradiated in the middle of the heating period. After a treatment
      with 32 Gy in 8 fractions combined with 8 heat fractions of 43 degrees C, 1hr,
      during 4 weeks, tumours showed an enhanced regression and growth delay in
      comparison to radiation alone. A thermal enhancement ratio (TER) of 1.4 was
      determined. Acute skin reactions were of minor importance. In conclusion, a
      simultaneous treatment of superficial tumours with infrared-A-hyperthermia and
      radiation at a therapy unit is relatively easy to perform and enhances
      considerably the therapeutic efficacy of a radiation treatment.

PMID- 9014514
TI  - Modification of radio-thermo-chemotherapy by AK-2123 and hydralazine in tumor
      bearing mice.
AB  - The effects of chemical modifiers of hypoxic radiosensitizer, a 3-nitrotriazole
      derivative AK-2123 (200 mg/kg) before treatment, and vasodilator of hydralazine
      (HDZ; 5.0 mg/kg) after treatment on tumor growth of SCCVII of mice were
      investigated in the radio-thermotherapy combined with mitomycin C (MMC; 2.0
      mg/kg) or adriamycin (ADM; 3 mg/kg). The tumor treated by 10 Gy alone (tumor
      doubling time = 7.5 days), MMC alone (6.9 days), and hyperthermia (43 degrees C,
      30 min; HT) alone (8.0 days) showed a slight growth delay (control: 5.6 days).
      Prolonged growth delay (23.2 days) was observed by MMC-radio-thermotherapy (MMC
      10Gy/HT) than that (12.4 days) by 10 Gy/HT. The modification of MMC-radio
      thermotherapy by HDZ administered between 10 Gy and HT (MMC-10 Gy/HDZ/HT)
      resulted in the significant prolongation of tumor growth delay (31.7 days). AK
      2123 administration before this treatment, (MMC-AK-2123)-10 Gy/HDZ/HT), enhanced
      a further tumor growth delay (37.6 days) which is equal to that by 50 Gy alone
      and resulted in the highest dose modifying factor (DMF) of 5.2. While
      modification of ADM-radio-thermotherapy by AK-2123 and HDZ, (ADM-AK-2123)-10
      Gy/HDZ/HT, gave the equal tumor growth delay to that by 30 Gy alone (DMF = 3.1).
      These high efficacies of radio-thermo-chemotherapy modified by AK-2123 and HDZ
      may be caused by tumor blood flow reduction.

PMID- 9014515
TI  - Radioprotective effect of whole-body hyperthermia on mice exposed to lethal doses
      of total-body gamma irradiation.
AB  - The whole-body hyperthermia (40 degrees C, 1 hr) 20-48 hr prior to total-body
      irradiation (TBI) with 9 Gy gamma rays gave 80% protection as assessed by
      survival of the animals. However this was reduced to 50% when mice were
      irradiated 7 or 15 days after hyperthermia. The local hyperthermia (42 degrees C,
      1 hr) given prior to irradiation, on the other hand, did not show any protective
      effect. The whole-body or local hyperthermia given after TBI had no protective
      effect on survival of animals.

PMID- 9014516
TI  - Protective effect of curcumin, ellagic acid and bixin on radiation induced
      toxicity.
AB  - Whole body irradiation of rats (10 Gy as five fractions) found to produce lung
      fibrosis within 2 months as seen from increased lung collagen hydroxyproline and
      histopathology. Oral administration of antioxidants curcumin, ellagic acid, bixin
      and alpha-tocopherol at a concentration 200 mumole/kg body weight significantly
      reduced the lung collagen hydroxyproline in these animals. In serum and liver
      lipid peroxidation which were found to be increased by irradiation was reduced
      significantly by antioxidant treatment. The liver superoxide dismutase and
      glutathione peroxidase activity were also found to be increased and catalase
      activity decreased in irradiated control. Superoxide dismutase activity reduced
      significantly by antioxidant treatment while catalase activity was found to be
      increased with alpha-tocopherol treatment. The increased frequency of
      micronucleated polychromatic erythrocytes after whole body irradiation of mice
      was found to be significantly reduced with antioxidants.

PMID- 9014517
TI  - Radioprotective effects of Rasayanas.
AB  - Oral administration of Rasayanas (indigenous preparations made up of herbal
      drugs) significantly increased total WBC count, bone marrow cellularity, natural
      killer cell and antibody dependent cellular cytotoxicity in gamma radiation (4
      Gy) exposed mice. Also, Rasayanas reduced radiation induced lipid peroxidation in
      liver. The possible mechanisms of action of Rasayanas could be increased stem
      cell proliferation and its effect on free radical induced injury produced by
      radiation.

PMID- 9014518
TI  - Modification of radiation induced changes in murine hepatic lipid profiles by
      garlic (Allium sativum Linn.) unsaturated oils.
AB  - Adult male Swiss albino mice were administered 74 kBq g-1 body weight of 45Ca in
      the presence and absence of garlic unsaturated oils, and the changes in total
      lipids, triglycerides, phospholipids and free fatty acids contents of liver were
      observed at various intervals from 1 to 14 days post-treatment. The results
      obtained indicate that garlic oils prevented rapid increase in hepatic total
      lipids, triglycerides and phospholipids and decrease in free fatty acids induced
      by radiocalcium and the values reached normal values earlier in garlic treated
      animals than in irradiated animals. Possible mechanism underlying the protective
      action of garlic oils is reported.

PMID- 9014519
TI  - Use of Withania somnifera Dunal as an adjuvant during radiation therapy.
AB  - Withania somnifera popularly known as Aswagandha is used in several indigenous
      drug preparations. Administration of a 75% methanolic extract of the plant was
      found to significantly increase the total WBC count in normal Balb/c mice and
      reduce the leucopenia induced by sublethal dose of gamma radiation. Treatment
      with W. somnifera was found to increase the bone marrow cellularity
      significantly, the percentage increase being 146.3. Treatment with W. somnifera
      had normalised the ratio of normochromatic erythrocytes and polychromatic
      erythrocytes in mice after the radiation exposure. Major activity of W. somnifera
      seemed to be in the stimulation of stem cell proliferation.

PMID- 9014520
TI  - Radiosensitizing effect of plumbagin on mouse melanoma cells grown in vitro.
AB  - Mouse melanoma cells were treated with plumbagin, a naphthoquinone, from the
      plant Plumbago rosea at 0.5 microgram/ml (PI) for 60 min either alone or followed
      by 2 Gy gamma radiation (RT). Response to the different treatments was assessed
      by following the cell growth up to 5 days post treatment. PI alone produced a
      significant decrease in the cell count on days 3 and 4, whereas RT treatment
      significantly enhanced the growth inhibitory effect when compared to RT or PI
      alone. These findings suggests the radiosensitizing effect of PI on mouse
      melanoma cells in vitro, supporting the earlier in vivo findings.

PMID- 9014521
TI  - Induction of apoptosis by ionizing radiation in Chinese hamster V79 cells and a
      radioresistant cell strain derived from V79.
AB  - DNA fragmentation into nucleosome ladder, a hall mark of apoptosis, could be
      obtained by as low as 0.58 Gy of gamma irradiation within 6 hr of irradiation
      which increased appreciably after 48 hr in V79 cells. In the same condition
      condensation of the nucleus and marginalization of the cytoplasm the
      characteristic morphology of apoptotic death were observed. Unirradiated controls
      had approximately 2% apoptotic cells. When cells were irradiated with 0.58 Gy,
      approximately 10% of the cells had the apoptotic morphology. This number
      increased to approximately 29% at 3.5 Gy dose. At a higher dose, apoptotic and
      necrotic cells were visualized. In radio resistant cells higher doses were
      required to induce morphological changes. The results indicated that gamma
      irradiation can induce apoptosis in Chinese hamster V79, fibroblast cell line and
      the radioresistant cell strain derived from V79 cells is also resistant to
      induction of apoptosis.

PMID- 9014522
TI  - Nuclear matrix bound DNA polymerase-beta in mouse fibrosarcoma: effect of gamma
      radiation.
AB  - Nuclear matrices isolated from the mouse fibrosarcoma tumour cells contain the
      eukaryotic replicative enzyme DNA polymerase-alpha and the presumptive repair
      enzyme DNA polymerase-beta. Exposure of tumors to various doses of gamma
      radiation (1.95 to 6.5 Gy) causes a 2-fold increase in the levels of only DNA
      polymerase-beta in the nuclear matrix. The increase in the levels of this enzyme
      is not discernible if the matrices are isolated 24 hr after irradiation. The rise
      in the levels of the repair enzyme DNA polymerase-beta could be indicative of
      radiation stress response of the tumour cells and their repair ability.

PMID- 9014523
TI  - Prognostic assays in multiple myeloma: correlated with flow cytometry.
AB  - DNA ploidy of plasma cells in bone marrow has been indicated to play a role in
      treatment response of multiple myeloma. Therefore, a prospective study was done
      to test this correlation. Univariate DNA flow cytometry was done on 13 proved
      multiple myeloma patients. Patients aged below 50 years showed hypodiploidy,
      irrespective of 'S' phase population, where as all patients above 50 years had
      diploidy or hyperdiploidy, except for one patient. Early stage patients (I & II)
      with less than 25% plasma cells in bone marrow were all aneuploids. Patients
      belonging to advanced clinical stage with more than 60% plasma cells in bone
      marrow with aneuploidy, especially hyperdiploidy (DI > 1.15), carried a poor
      prognosis. It was difficult to correlate the 'S' phase fraction with other
      parameters from the present data. Further study with BrdU labelling to determine
      the proliferative status of the 'S' phase cells is needed.

PMID- 9014524
TI  - Extrapolated response dose as a potential tool in radiotherapy and chemo
      radiotherapy of head and neck cancers.
AB  - An analysis of head and neck cancer patients treated by radiotherapy (RT) alone
      (114 patients) and by chemo-radiotherapy (RT + CT) (115 patients) was carried
      out; the doses varied from 40-77 Gy and 35-71 Gy in RT and RT + CT groups
      respectively. The chemotherapy (CT) (induction/concurrent) drugs used were 5-FU,
      cisplatin, methotrexate either single or in combination. Extrapolated response
      dose values were evaluated with alpha/beta values of 10, 2.5 and 6 Gy for acute,
      late complications and tumour response, respectively. Dose enhancement factor
      (DEF) and Therapeutic gain factor (TGF) values were evaluated on the basis of ERD
      for patients receiving 5-FU RTCT (72 patients). ERD vs late complication rate and
      response rate curves were drawn for RT, RT + CT (< 7 cycles), RT + CT (> 6
      cycles) and RT + CT (cumulative). DEF values for response rate were 0.95, 0.95
      and 0.82 for the three RT + CT groups respectively. Similarly DEF values for late
      complication rate were evaluated as 0.87, 0.93 and 0.88. TGF values for RT + CT
      were 1.09, 1.02 and 0.93. TGF values indicated lack of significant influence of
      CT on clinical outcome. The correlation of ERD with late complication, response
      and status at last follow up (NED) was statistically significant for both groups
      (P < 0.01). ERD did not correlated with acute complication in RT group (P >
      0.01). From the present analysis, in RT + CT treatments of head and neck cancers,
      an ERD value of 69 Gy is suggested as the limit for an acceptable 5% late
      complication rate.

PMID- 9014525
TI  - Hearing anomalies following radiation therapy for head and neck cancers.
AB  - Ionizing radiation used for the treatment of head and neck tumors affected
      epithelial and connective tissue. Epithelial lining of the middle ear mucosa
      desquamated, when exposed to conventional dose of radiation. Mucosa becomes
      oedematous which subsequently lead to formation and collection of sterile fluid
      within middle ear cavity and thus producing radiation otitis media with
      conductive deafness. Radiation induced changes in the structure surrounding the
      end organs of hearing such as vascular and connective tissue alterations which
      later eventually could affect the end organ leading to perceptive type of hearing
      loss as a result of chronic anoxia to end organ.

PMID- 9014526
TI  - Effect of gamma radiation on fetal haemopoiesis of mouse.
AB  - Effect of a single acute exposure to gamma-rays during the late fetal period on
      the fetal haemopoietic tissue of mouse was studied. Pregnant Swiss albino mice
      were exposed to 1 Gy of gamma-rays on day 17 post coitus (late fetal period) and
      24 hr after exposure the fetuses were observed for changes in the liver weight,
      cytogenetic damage in liver cells by micronucleus (MN) induction and stem cell
      survival by spleen colony (CFU-S) assay. Irradiation resulted in a significant (P
      < 0.01) decrease in fetal liver weight. A significant (P < 0.001) increase in MN
      count was observed after exposure, while CFU-S displayed a significant (P <
      0.001) reduction in the cell survival as compared to the sham-treated control.
      These results demonstrate the high susceptibility of mouse fetal haemopoietic
      system to radiation.

PMID- 9014527
TI  - Postnatal survival and growth of mouse irradiated in utero with low dose.
AB  - In order to investigate radiation risks associated with low dose and low dose
      rates, pregnant Swiss albino mice were exposed to gamma rays, 0.80 Gy from a
      cobalt-60 source at two different dose-rates (0.0795 and 0.0012 Gy/min) on 18 day
      post conception. In females exposed to lower dose-rate (0.0012 Gy/min), litter
      size was found to be decreased, while those exposed to higher dose-rate (0.0795
      Gy/min), it remained unaltered. In both groups, appearance of fur and development
      of complete fur were delayed, whereas gait was delayed only in higher dose-rate
      group. Male offspring exhibited a biphasic mode of weight loss, while female
      offspring after an initial weight loss at 1 week, displayed a continuous
      recovery, but could not attain the normal weight till 12 weeks of age. It appears
      that higher dose-rate is more effective in delaying the appearance of
      physiological markers and weight loss, while in terms of litter size lower dose
      rate (0.0012 Gy/min) is more effective.

PMID- 9014528
TI  - Long-term effect of prenatal exposure to low level of gamma radiation on
      neurophysiology of mouse.
AB  - Abdominal region of pregnant Swiss mice were exposed to 0.25, 0.35 or 0.50 Gy of
      gamma radiation on days 11.5, 12.5, 14.5 or 17.5 post coitus (pc). Changes in
      locomotory activity and learning performance, and hippocampal biogenic amines
      (noradrenaline, NA; dopamine, DA; 5-hydroxytryptomine, 5-HT; and 5-HTs metabolite
      5-hydroxyindolacetic acid, 5-HIAA) were studied at 12 (adult) and 18 months (old)
      of age. Significant change in locomotory activity and learning performance was
      observed after exposure to 0.50 Gy at late organogenesis day (11.5 pc), when
      tested at 12 months of age, but not observed much change at 18 months. Biogenic
      amines did not show any significant change after any exposure dose at any of the
      gestation days. It was inferred from the results that gamma irradiation (0.50 Gy)
      at the late organogenesis (day 11.5 pc) can impair the brain functions in adults
      when normal faculties are functional.

PMID- 9014529
TI  - Radiobiological effects of low doses of tritiated water on developing mouse
      cerebellum from 17th day post-coitum.
AB  - Pregnant Swiss albino mice were maintain on tritiated drinking water of the
      activity of 111 and 11.1 kBq/ml after a priming injection of 74 and 7.4 kBq/ml
      body water respectively from 17th day of gestation till parturition. Animals were
      autopsied on 1, 2, 3, 4, 5 and 6 weeks postpartum and studied for cerebellar
      vulnerability. Cerebellum suffered from radiopathological changes in 1, 2 and 3
      weeks age groups of mice in terms of degeneration and loss of Purkinje cells
      leading to formation of empty basquets, vacuolation in molecular layer and
      interfoliar connective tissue and pycnosis in granule cells of granular cell
      layer at 11.1 kBq dose level. Mice of 4, 5 and 6 weeks age groups, being
      relatively radioresistant, showed lesser changes in comparison with 1 to 3 week
      old mice. Though, the nature of the damage remained the same, it tended to
      intensify at 111 kBq dose thereby reflecting a dose dependent variation.

PMID- 9014530
TI  - Changes in mouse behavior induced by fetal exposure to diagnostic ultrasound.
AB  - Pregnant Swiss albino mice were exposed to diagnostic ultrasound (3.5 MHz, 65mw,
      ISPTP = 1 W/cm2, ISATA = 240 W/cm2) for 10 min on day 14, 16 or 17 of gestation
      to assess any changes in physiological reflexes (pinna detachment, eye opening
      and fur development) and postnatal mortality. Changes in locomotor activity by
      open field test and dark/bright arena test and learning and memory by hole board
      test were also recorded. No change was observed in physiological reflexes and
      postnatal mortality. However there were significant alterations in behavior in
      all the three exposed groups. These results demonstrate that ultrasound exposure
      during the late fetal period can impair brain function in adult mouse.

PMID- 9014531
TI  - Detection of an ascorbate radical in an irradiated mice using electron spin
      resonance (ESR).
AB  - Ascorbate radical (Asc.-) produced by the reaction of AscH- (ascorbic acid) with
      HO or O2.- after irradiation in mice has been measured. It is possible to measure
      Asc.- easily using ESR and a dialysis method in which Asc.- is collected at room
      temperature in the interstitial fluid through the dialysis membrane. After
      irradiation, Asc.- increases in both normal muscle and tumor tissues (SCC-VII) in
      proportion to the radiation dose. These results suggest that the amount of HO and
      O2.- produced is reflected in the Asc.- production. This method has been found
      more useful for the following reasons, (i) no special treatment, such as freezing
      of the sample, and no administration of noxious agents are necessary to measure
      Asc.-, (ii) irradiation using a dose of only a few Gy shows an increase in
      production of Asc.-, and (iii) this method dose not require removal of organs.
      Using this method, Asc.- can serve as an indicator of the amount of HO and O2.-
      produced by irradiation in vivo.

PMID- 9014532
TI  - Detection of superoxide dismutase isozymes in normal and X-irradiated chick
      amniotic fluid by using isoelectric focussing.
AB  - Isoelectric focussing of amniotic fluid of chick system over pH gradient of 4-6
      revealed presence of 8 superoxide dismutases. The superoxide dismutase (SOD)
      isozymes were identified as one major isozyme and other seven were minor ones.
      Higher expression of SOD (major isozyme) with exposure of 1000 R was studied. The
      isoelectric point (pI) of major SOD isozyme in control (5) differs from radiation
      exposed samples (5.12). Hence in radiation exposed amniotic fluid showed more
      pronounced SOD major isozyme, than control amniotic fluid. It is clearly evident
      that the SOD isozyme with X-irradiation having different isoelectric points, may
      lead to modification of the amino acid composition and charges of amino acids in
      the protein structure of SOD. So, the higher SOD isozyme expression has a role in
      defence action against free radical damage by X-irradiation during embryonic
      development.

PMID- 9014533
TI  - Possible role of glutathione in resistance to heavy metals and hydrogen peroxide
      in a radioresistant Chinese hamster V79 cell strain.
AB  - To understand the cellular and biochemical nature of radioresistance in the
      strain M5 derived from Chinese hamster V79 cells, the sensitivity of the
      resistant cells towards CdCl2, Zn(Ac)2, and H2O2 by the colony forming ability
      has been tested. D0 values for these compounds in Chinese hamster V79 cells were
      5.4 microM, 27.8 microM and 4.3 micrograms/ml respectively while for M5 cells
      these were 8.3 microM, 142.9 microM and 11.9 micrograms/ml respectively. The
      resistance to heavy metals as well as the oxidative damage could be reversed by
      the inhibition of glutathione synthesis by the drug buthionine sulfoximine (BSO).
      These set of data indicate that the cellular antioxidant glutathione plays an
      important role in the observed oxidant-resistant phenotype as well as heavy metal
      resistance in M5 cells.

PMID- 9014534
TI  - Radio-adaptive response in human lymphocytes in vitro.
AB  - An attempt has been made to investigate the adaptive response to ionizing
      radiation in the human lymphocytes in vitro using cytochalasin-B blocked
      micronucleated binucleate cells (mn-BNCs) as a cytogenetic end point. Whole blood
      samples drawn from healthy donors, of either sex were irradiated in vitro at a
      dose of 1 cGy (adaptive or conditioning dose) Cobalt-60 gamma radiation (dose
      rate 1.12 cGy/min) at about 26 hr after mitogenic stimulation. After 31 hr of
      their initiation, groups of cultures were subsequently exposed to a challenging
      dose of 100 cGy gamma radiation (dose rate 82 cGy/min.). Eight males in the age
      group ranging from 25 to 55 years and eight females (age group 25 to 29 years),
      have been analysed during this study. Analysis of data revealed 40.6% reduction
      in the frequency of mn-BNCs among the males with a range from 25.7% to 54.7%. In
      case of females, also the per cent reduction varied from 26.3% to 49.0%, with a
      mean value of 33.7%. Pooling the data from males and females gave an overall
      reduction of 37.1% in the frequency of radiation induced mn-BNCs due to pre
      exposure to 1 cGy radiation.

PMID- 9014535
TI  - 17th Annual meeting of the Society of Perinatal Obstetricians. Anaheim,
      California, January 20-25, 1997. Abstracts.

PMID- 9014536
TI  - American College of Cardiology 46th annual scientific session. Anaheim,
      California, March 16-19, 1997 Abstracts.

PMID- 9014537
TI  - Academic anaesthetists--an endangered species?

PMID- 9014538
TI  - The effect of the National Confidential Enquiry into Perioperative Deaths on
      clinical practice. Report of a postal survey of a sample of consultant
      anaesthetists.
AB  - A postal survey was performed to investigate whether the National Confidential
      Enquiry into Perioperative Deaths (NCEPOD) had influenced clinical practice. A
      short questionnaire was sent to 100 consultant anaesthetists from England, Wales
      and Northern Ireland. There was a 72% response rate. NCEPOI) had influenced
      personal clinical practice in 74% of respondents, the inception of guidelines and
      protocols in 75% and had helped in the improvement of essential services, staff
      or equipment in 80%. Some individuals had tried and failed to establish
      improvements. Nearly 80% perceived current threats to standards of care that
      NCEPOD might investigate in the future. The replies indicated that NCEPOD is
      perceived by clinicians as influencing clinical practice and standards of care.

PMID- 9014539
TI  - Why do patients die on general wards after discharge from intensive care units?
AB  - The aim of this study was to determine the cause of death of those patients who
      died on general hospital wards after discharge from an intensive care unit. Of
      1700 patients admitted over a 5-year period, 341 (20%) died in intensive care but
      a further 153 (9%) died on general wards. From data recorded at discharge from
      intensive care, 54.2% of those who died on the wards were considered at risk of
      death, 25.5% were expected to die but 20.3% were expected to survive. The main
      causes of death were pneumonia, hypoxic or structural brain damage,
      cerebrovascular accident, malignancy, myocardial infarction, renal or multi-organ
      failure and sepsis. Some of these may have been preventable with further
      intensive care or improved care on the wards.

PMID- 9014540
TI  - Short Form 36 in the intensive care unit: assessment of acceptability,
      reliability and validity of the questionnaire.
AB  - The aim of this study was to assess the acceptability, validity and reliability
      of the Short Form 36 quality of life questionnaire in 166 adult patients
      following discharge from a general intensive care unit. Reliability was
      quantified by measuring internal consistency using correlation among items and
      Cronbach's alpha coefficient. Reliability coefficients were calculated from two
      way analysis of variance. Construct validity was tested by examining differences
      in scores between sex and age groups. Content validity was reflected by the
      spread of dimension scores. Acceptability to patients appeared reasonable,
      although considerable nursing time was required to administer the questionnaire.
      The measures of reliability exceeded recognised statistical standards in all but
      two instances. Construct validity was confirmed by lower scores being reported by
      women and older age groups. The scores of six of the eight dimensions were spread
      throughout the entire range of possible scores suggesting acceptable content
      validity.

PMID- 9014541
TI  - Accidental bronchial intubation. An analysis of AIMS incident reports from 1988
      to 1994 inclusive.
AB  - Accidental bronchial intubation was examined in the first 3947 cases reported to
      the Australian Incident Monitoring Study and was found to have accounted for 154
      (3.7%) of the total incidents reported. Most incidents were detected in the
      operating theatre (93.5%) and during maintenance of anaesthesia (77.9%), by
      unexplained oxygen desaturation alone (63.6%). Capnography remained normal or
      unremarkable during 88.5% of the episodes. One-third of cases were associated
      with head or neck surgery and possible flexion of the patient's head. A RAE tube
      was used in 20% of incidents, a greater frequency than occurred in the study
      overall. A third party was implicated in 36 (23.4%) of cases. Ninety per cent of
      cases were considered preventable. Major morbidity occurred in three cases and
      unplanned intensive care admission was required in a further five. Almost two
      thirds (61.1%) of the incidents might have been avoided by the proposed markings
      on the tracheal tube. We conclude that when arterial desaturation occurs at any
      stage during anaesthesia the possibility of bronchial intubation must be
      considered. Asymmetrical ventilation may be difficult to detect clinically and in
      most cases there is no change in capnography.

PMID- 9014542
TI  - The minimum effective doses of pethidine and doxapram in the treatment of post
      anaesthetic shivering.
AB  - This study was designed to find the minimum effective doses of doxapram and
      pethidine to stop post-anaesthetic shivering. Two hundred and twenty healthy
      patients who shivered following routine surgery were allocated randomly to
      receive one of 10 doses of doxapram (0.18, 0.23, 0.29, 0.35, 0.41, 0.47, 0.7,
      0.93, 1.17 and 1.4 mg.kg-1), one of five doses of pethidine (0.12, 0.18, 0.23,
      0.29 and 0.35 mg.kg-1) or saline. Probit analysis demonstrated that the number of
      patients who stopped shivering with doxapram was independent of the amount of
      drug given in this dose range. The lowest dose of doxapram (0.18 mg.kg-1) was
      significantly more effective than placebo (p < 0.01). For pethidine there was a
      dose-dependent effect on shivering to a maximum of 95% of patients successfully
      treated with 0.35 mg.kg-1. We conclude that 0.35 mg.kg-1 of pethidine is the
      minimum dose required to treat post-anaesthetic shivering effectively. We also
      conclude that 0.18 mg.kg-1 of doxapram is as effective as 1.4 mg.kg-1 in the
      treatment of post-anaesthetic shivering. Further study is required to find the
      minimum effective dose of doxapram.

PMID- 9014543
TI  - Prediction of infusion rates of rocuronium using the bolus test dose technique.
AB  - Twenty-four patients were given a loading dose of rocuronium 1.0 mg.kg-1
      intravenously followed by boluses of 20 mg (n = 19) and 10 mg (n = 24) after
      return of T1 of the train-of-four to 5% of control. Neuromuscular function was
      assessed using a Relaxograph. The time was recorded for the return of T1 to 5%
      after the administration of the boluses and subsequently an infusion of
      rocuronium was started. The aim was to maintain T1 between 3% and 7% of control
      for at least 40 min without a change of infusion rate. The correlations between
      the duration of the test doses and the infusion rates were -0.94 (10 mg) and 
      0.86 (20 mg). The predictive accuracy of the 10 mg bolus was assessed in a
      further 10 patients. At the termination of the infusion three patients had a T1%
      that was outside the desired range of 3-7%. A 10 mg bolus that lasts 6 min
      indicates a need for an infusion of at least 60 mg.h-1, 8 min (50 mg.h-1), 10 min
      (40 mg.h-1), 15 min (30 mg.h-1), 24 min (20 mg.h-1) and 34 min (15 mg.h-1).

PMID- 9014544
TI  - Comparison of computer-controlled administration of propofol with two manually
      controlled infusion techniques.
AB  - Ninety women were studied in order to compare dose requirements and quality of
      anaesthesia between target-controlled infusion and two manually controlled
      infusion schemes for propofol administration: group I received target-controlled
      infusion for induction (4 micrograms.ml-1 target blood concentration, increased
      by 2 micrograms.ml-1 after 3 min of consciousness not lost), groups II and III
      received an induction bolus of propofol at infusion rates of 1200 or 600 ml.h-1,
      respectively, until loss of consciousness. Anaesthesia was maintained with
      propofol target-controlled infusion in group 1 or by constant rate infusion in
      the other two groups. Computer simulations were used to calculate blood and
      effect-site propofol concentrations. Mean induction times (SD) were 78 (65)s in
      group I versus 51 (10)s and 62 (12)s in groups II and III, respectively (p < 0.05
      between groups II and III). Mean induction doses were: 1.31 (0.44), 2.74 (0.56)
      and 1.77 (0.43) mg.kg-1 and mean maintenance doses were 13.4 (3.55), 9.32 (1.72)
      and 9.97 (1.53) mg.kg-1 h-1 in groups I, II and III, respectively (p < 0.05
      between all groups). There was a lower incidence of apnoea in group I than in
      groups II and III. There were no significant differences between the groups in
      other objective parameters of anaesthetic quality studied. Computer simulations
      showed an "overshoot' in propofol blood and effect-site concentration with manual
      induction and significantly higher maintenance levels with target-controlled
      infusion.

PMID- 9014545
TI  - Long-term outcome after percutaneous dilational tracheostomy. Endoscopic and
      spirometry findings.
AB  - We studied 41 patients who had previously undergone percutaneous dilational
      tracheostomy at least 6 months following tracheal decannulation. The patients
      were examined using laryngotracheoscopy and spirometry to assess the long-term
      anatomical and functional consequences of percutaneous dilational tracheostomy.
      Apart from one patient who had requested a scar revision, no patient was
      symptomatic. A significant (> 10%) tracheal stenosis was identified in four
      asymptomatic patients, two of whom also had spirometric evidence of this
      obstruction. These results suggest that the long-term outcome after percutaneous
      tracheostomy is at least as good as that following conventional surgical
      tracheostomy. Refinements of the percutaneous technique, such as endoscopic
      guidance, may further improve the results.

PMID- 9014546
TI  - An alternative method of nitrous oxide delivery into a minimal-flow circle
      breathing system.
AB  - We have sought to define a way in which nitrous oxide can be safely and
      universally used at minimal to low flows by utilising a circle system with a
      controlled leak provided by a standard gas analyser sampling line and a fresh gas
      supply of 50% nitrous oxide in oxygen, entering from a trunk interposed between
      the ventilator and the circle system. Although preliminary calculations suggested
      that this arrangement was likely to work, it was found that 13 of 23 patients
      studied prospectively developed an inspired oxygen fraction below 0.3. We
      conclude that, although this arrangement provides a new means of introducing
      nitrous oxide into the circle breathing system, it does not appear inherently
      safer or more convenient than the conventional route.

PMID- 9014547
TI  - Epidural blood patch for atypical headache following obstetric epidural
      analgesia.
AB  - A case of atypical headache presenting following otherwise unremarkable epidural
      analgesia in labour is presented. Although there was no suggestion of accidental
      dural puncture during insertion of the epidural catheter, and despite the unusual
      features of the headache and complicated case history, an epidural blood patch
      was performed 13 weeks post-partum, with improvement of the patient's symptoms. A
      repeat epidural blood patch 2 weeks later completely resolved her headache.

PMID- 9014548
TI  - Carbon dioxide embolism during laser endometrial ablation.
AB  - A patient undergoing endometrial ablation with an Nd-YAG laser, a carbon-dioxide
      cooled coaxial fibre and an exposed fibre tip suffered a carbon dioxide embolism
      resulting in cardiac arrest. A full recovery was made with no neurological
      deficit.

PMID- 9014549
TI  - Anaesthetic management of childhood thyrotoxicosis and the use of esmolol.

PMID- 9014550
TI  - Tracheal dilatation complicating prolonged tracheal intubation.
AB  - A patient with severe acute respiratory distress syndrome requiring prolonged
      tracheal intubation and mechanical ventilation is described. Tracheal dilation
      was noted to have occurred following an elective surgical tracheostomy.
      Eventually, the patient was successfully weaned from mechanical ventilation and
      the tracheostomy tube removed.

PMID- 9014551
TI  - The anaesthetist and the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is a paradoxical disease state with in vitro
      prolongation of activated partial thromboplastin time and a strong predilection
      for in vivo thrombosis. The syndrome can be associated with systemic lupus
      erythematosus or lupus-like diseases or may be primary, presenting with
      thrombotic phenomena in young patients with no risk factors for thrombosis. We
      present two cases seen in two different settings in the hospital.

PMID- 9014552
TI  - The effect of laryngeal mask airway insertion on the position of the internal
      jugular vein.
AB  - A high-quality ultrasound system (Dyasonics Prisma) was used to study the effect
      of laryngeal mask airway insertion and cuff inflation on the position and
      relations of the internal jugular vein in eight healthy young patients undergoing
      elective surgery. On insertion of the laryngeal mask, with the cuff pre-inflated
      with 10 ml of air, some minor movement was discernible in the larynx. Neither the
      larynx nor surrounding structures changed significantly in position. However, on
      full inflation of the laryngeal mask cuff there was a more noticeable movement of
      the larynx, which visibly distended in an anterior direction. The mean anterior
      displacement was 0.8 cm (range 0.6-1.1 cm). There was no significant lateral
      displacement of the carotid artery or internal jugular vein and there was no
      significant compression of these structures. We conclude that in the presence of
      a laryngeal mask airway fixed landmarks such as the sternal notch and angle of
      the jaw should be used to identify the likely position of the internal jugular
      vein. Difficulty in cannulation may be experienced if the mobile laryngeal
      structures are used as landmarks.

PMID- 9014553
TI  - Music in theatre: not so harmonious. A survey of attitudes to music played in the
      operating theatre.
AB  - Music played to staff in the operating theatre is thought to improve surgeons'
      concentration but its effects on other theatre staff are unknown. We surveyed 200
      anaesthetists to determine the prevalence of music playing in the operating
      theatre and anaesthetists' attitudes to it. The response rate was 72% and of
      these 72% (104) worked in a theatre where music was played regularly. Around 26%
      of the sample felt that music reduced their vigilance and impaired their
      communication with other staff while 11.5% felt that music might distract their
      attention from alarms. Fifty-one per cent felt that music was distracting when a
      problem was encountered during the anaesthetic.

PMID- 9014554
TI  - Pre-operative hypertension--true or false?

PMID- 9014555
TI  - Ethics in obstetric anaesthesia.

PMID- 9014556
TI  - Cricoid pressure: are two hands better than one?

PMID- 9014557
TI  - What's in a name?

PMID- 9014558
TI  - PaCO2 and apnoea testing for brain stem death.

PMID- 9014559
TI  - Accuracy of pulse oximetry in aortomyoplasty and balloon counterpulsation.

PMID- 9014561
TI  - Re-inventing the wheel.

PMID- 9014560
TI  - Electrical failure in theatre--a consequence of complacency?

PMID- 9014562
TI  - General anaesthesia versus inhalational sedation for children's exodontia.

PMID- 9014563
TI  - Another complication of radial artery cannulation.

PMID- 9014564
TI  - Study power inadequate to reject ondansetron.

PMID- 9014565
TI  - Silent myocardial ischaemia and fluid absorption.

PMID- 9014566
TI  - Lignocaine toxicity--a surgical surprise.

PMID- 9014567
TI  - Emergency transtracheal ventilation.

PMID- 9014568
TI  - Difficult intubation in a neurosurgical patient.

PMID- 9014569
TI  - Midazolam co-induction and laryngeal mask insertion.

PMID- 9014570
TI  - A problem with nitric oxide cylinders.

PMID- 9014571
TI  - An unusual cause of tracheal tube cuff damage.

PMID- 9014572
TI  - The effect of pretreatment with ketorolac on pain during intravenous injection of
      propofol.

PMID- 9014573
TI  - Case report of a case report--who owns the data?

PMID- 9014574
TI  - Mathematical formulae for assessing the depth of the epidural space in children.

PMID- 9014575
TI  - Intrapulmonary shunt during one-lung anaesthesia.

PMID- 9014576
TI  - The epidemiology of pain: the more you have, the more you get.

PMID- 9014577
TI  - How vigorously should we exercise our rheumatoid arthritis patients?

PMID- 9014578
TI  - Hypertrophic osteoarthropathy following aortic surgery.
AB  - Unilateral lower extremity hypertrophic osteoarthropathy may be the initial
      symptom of an infected aortic graft. Knowledge of this uncommon association
      should lead to early and accurate diagnosis and appropriate surgical management,
      thus avoiding the development of aortoenteric fistula, a complication that still
      carries a significant risk of mortality.

PMID- 9014579
TI  - Relation between insulin-like growth factor-I concentrations, osteoarthritis,
      bone density, and fractures in the general population: the Chingford study.
AB  - OBJECTIVE: To assess the association between serum insulin-like growth factor-I
      (IGF-1) concentrations and osteoarthritis, and bone mineral density, and
      fractures in a large group of middle aged women from the general population.
      METHODS: 761 women aged 44-64 years from the Chingford study had serum IGF-I
      concentrations measured; hand, hip, spine, and anteroposterior weight bearing
      knee radiographs taken; and dual energy x ray absorptiometry (DEXA) scans of the
      hip and spine. X rays were scored using the Kellgren and Lawrence system. In
      addition knee x rays were scored using a standard atlas for individual features
      of osteophytes and joint space narrowing (both graded 0-3). IGF-I concentrations
      were adjusted for the effects of age. RESULTS: In the osteoarthritis analysis
      results were compared to a constant group of 155 subjects with no evidence of
      osteoarthritis at any site. There was no significant difference in serum IGF-I
      between these subjects and 606 subjects with osteoarthritis at any site. When
      individual sites were analysed, serum IGF-I was higher in those cases with more
      severe bilateral knee osteoarthritis and in those with distal interphalangeal
      (DIP) joint disease. There was no significant association between serum IGF-I and
      other forms of osteoarthritis or milder forms of knee osteoarthritis. There was
      no correlation between IGF-I concentrations and bone mineral density at the spine
      or hip, nor any difference between IGF-I concentrations in subjects with and
      without a history of non-traumatic fracture [22.8 (SD 6.6) v 23.1 (SD 6.6) nmol
      litre-1, P = 0.6] CONCLUSIONS: There is a modest association between IGF-I
      concentrations and the development of DIP osteoarthritis and more severe or
      bilateral knee joint osteoarthritis in women from the normal population, but no
      association with other forms of osteoarthritis, bone density, or fractures.

PMID- 9014580
TI  - Assessing progression of patellofemoral osteoarthritis: a comparison between two
      radiographic methods.
AB  - OBJECTIVE: To compare two plain radiographic methods for sensitivity to detect
      progression of patellofemoral osteoarthritis. METHODS: Two sets of paired skyline
      and lateral knee radiographs from 54 hospital referred patients (108 knees) with
      knee osteoarthritis were taken an average of 31 months apart (range 12-40). Films
      were examined separately in random order by a single observer blind to patient
      identity and time order. Minimum joint space was measured by metered caliper;
      individual features of osteoarthritis were graded 0-3 using an atlas. RESULTS:
      Intraobserver reproducibility assessed on 40 knees was to within +/- 0.5 mm for
      skyline lateral facet and +/- 0.7 mm for medial facet and lateral views. On the
      lateral view measured joint space decreased in 51% of knees but increased in 43%,
      with overall no significant mean group change with time (-0.2 mm, 95% confidence
      interval, 0.1 to -0.5). By contrast on the skyline view joint space decreased in
      at least one facet in 71% of knees, with significant decrease in mean joint space
      for both lateral facets (-0.4 mm, 95% CI, -0.2 to -0.6) and medial facets (-0.5
      mm, 95% CI, -0.1 to -0.8). CONCLUSIONS: It is possible to detect significant
      joint space loss with time on the skyline view that is not apparent on the
      lateral view. The skyline view should be the method of choice to detect
      progression of patellofemoral osteoarthritis.

PMID- 9014582
TI  - Complement in acute and chronic arthritides: assessment of C3c, C9, and protectin
      (CD59) in synovial membrane.
AB  - OBJECTIVES: To investigate the role of complement cascade induced damage and
      protection against it in acute arthritides compared to rheumatoid arthritis and
      other chronic joint derangements. METHODS: C3c, C9, and protectin (CD59) were
      examined by avidin-biotin-peroxidase complex staining. RESULTS: Marked deposits
      of C3c and C9 were found in synovial vasculature and intercellular matrix of the
      lining in rheumatoid arthritis and in acute arthritides (including bacterial,
      reactive, and osteoarthritis flare up). Furthermore, protectin was not visible in
      synovial lining cells and was relatively weakly expressed in stromal and
      endothelial cells in rheumatoid arthritis; also in acute arthritides protectin
      expression was weak. In contrast, C3c and C9 deposits were not found in chronic
      conditions associated with degenerative diseases (osteoarthritis and
      osteochondritis dissecans) or mechanical causes (patellar luxation and a ruptured
      meniscus), in which also the protectin expression was prominent in synovial
      lining, endothelial and some stromal cells. CONCLUSIONS: Activation of the
      complement in rheumatoid arthritis and in acute arthritides seems to be
      associated with a decreased protection of synovial cells against cellular effects
      and lysis mediated by membrane attack complex.

PMID- 9014581
TI  - Effect of sustained loading on the water content of intervertebral discs:
      implications for disc metabolism.
AB  - OBJECTIVE: To examine regional changes in the fluid content of human
      intervertebral discs by comparing sagittal plane "profiles" of hydration before
      and after mechanical loading. METHODS: Cadaveric lumbar intervertebral discs were
      loaded to simulate a typical day's loading in vivo. Ten motion segments were
      subjected to a 1500 N compressive load for a period of 6 h with the superior
      vertebrae inclined by 4-8 degrees to simulate a slightly flexed posture.
      Immediately after loading the discs were frozen at -80 degrees C. Subsequently
      they were cut into slices perpendicular to the sagittal midline of the disc, and
      each slice was weighed before and after freeze drying. This enabled a profile of
      fluid content across the disc to be constructed. Fluid loss due to loading was
      estimated by comparing the water content of each loaded disc with that of an
      adjacent unloaded disc from the same spine. RESULTS: After 6 h of creep loading,
      disc height approached, but did not quite reach, an equilibrium. The mean fluid
      loss from all discs was 18%. All regions except the outer 2 mm experienced a
      significant loss of fluid (P < 0.01). The posterior mid-annulus showed the
      greatest fluid loss (30%), while the nucleus lost 15%. CONCLUSIONS: A comparison
      with previously published work suggests that fluid exchange of this magnitude
      will have a considerable effect on disc cell metabolism and on metabolite
      transport.

PMID- 9014583
TI  - Annexin V autoantibodies in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the occurrence of anti-annexin V autoantibodies in sera
      of patients with rheumatoid arthritis to assess involvement with the disease and
      any relation to glucocorticoid treatment. METHODS: Anti-annexin V antibodies were
      measured by an enzyme linked immunosorbent assay (ELISA) which used the purified
      human recombinant protein as antigen. RESULTS: Concentrations of anti-annexin V
      autoantibodies, predominantly of the IgG class, were significantly raised in sera
      from patients with rheumatoid arthritis compared to normal controls. This was not
      correlated with other indices of disease activity such as erythrocyte
      sedimentation rate or C reactive protein and was unrelated to glucocorticoid
      treatment. CONCLUSIONS: Extracellular annexin V provides an antigenic stimulus
      for autoantibody production and its in vivo expression is independent of
      glucocorticoid control. Such autoantibodies may have a detrimental role in the
      arthritic condition by interfering with putative functions of annexin V,
      including collagen type II binding, inhibition of phospholipase A2 activity, and
      Fc receptor activity.

PMID- 9014584
TI  - Development of a functional scoring system for rheumatoid arthritis patients with
      cervical myelopathy.
AB  - OBJECTIVE: To be able to measure disability objectively in rheumatoid arthritis
      complicated by cervical myelopathy. METHODS: The responses to the Stanford health
      assessment questionnaire disability index were recorded from 250 consecutive
      patients (group 1) referred to our unit for spinal surgery. Using principal
      components analysis the questionnaire was reduced from 20 questions to 10
      questions. In the second part of the study, the results of the questionnaire for
      those patients undergoing surgery from the original group of 250 patients were
      analysed with respect to outcome. RESULTS: The reduction in the number of
      questions results in no significant loss of information, reliability (internal
      consistency Cronbach's alpha = 0.968) or sensitivity. The new scale, the
      myelopathy disability index, measures only one dimension (Eigen value 6.97) and
      may be more finely tuned to the measurement of disability in these myelopathic
      patients. When administered to the 194 patients undergoing cervical spine (group
      2) surgery the myelopathy disability index was an accurate predictor of
      neurological and functional outcome, as well as survival following surgery (P <
      0.0001). CONCLUSIONS: The myelopathy disability index provides a much needed
      objective and reliable means of assessing disability in patients with rheumatoid
      involvement of the cervical spine and also in predicting outcome following
      surgical intervention. It also provides information for both the patient and
      surgeon alike, on what to realistically expect from surgery. Its adoption should
      facilitate comparisons between different forms of surgical intervention.

PMID- 9014585
TI  - Shoulder capsulitis in type I and II diabetic patients: association with diabetic
      complications and related diseases.
AB  - OBJECTIVE: To examine the association between shoulder capsulitis and chronic
      diabetic complications and diseases closely related to diabetes. METHODS: A cross
      sectional study in 291 type I [mean (SD) age 33.2 (9.9) years] and 134 type II
      [61.1 (12.4) years] diabetic patients. The presence of shoulder capsulitis,
      Dupuytren disease, and limited joint mobility was sought. The patients were
      assessed for background and proliferative retinopathy, nephropathy, autonomic
      neuropathy, and peripheral symmetrical somatic polyneuropathy. Diseases closely
      related to diabetes (hypertension, history of myocardial infarction, coronary
      heart disease, and peripheral vascular disease) were also recorded. RESULTS:
      Prevalence of shoulder capsulitis was 10.3% in type I and 22.4% in type II
      diabetic subjects. Shoulder capsulitis was associated with the age in types I (P
      < 0.01) and II (P < 0.05) diabetic patients, and with the duration of diabetes in
      type I patients (P < 0.01). Odds ratios for autonomic neuropathy in type I and
      type II diabetic subjects with shoulder capsulitis were 4.1 (95% confidence
      interval, 1.6 to 10.9) and 2.7 (95% CI, 1.1 to 7.0), respectively, after
      controlling for age and duration of diabetes. Odds ratio for history of
      myocardial infarction in type I diabetic subjects with shoulder capsulitis was
      13.7 (95% CI, 1.3 to 139.5) after controlling for age, duration of diabetes,
      hypertension, and smoking habits. Other associations between shoulder capsulitis
      and diabetic complications, related diseases, and other hand abnormalities were
      fully explained by age and the duration of diabetes. CONCLUSIONS: Shoulder
      capsulitis is common in type I and type II diabetic patients. It is associated
      with age in type I and II diabetic patients and with the duration of diabetes in
      type I patients. It is associated with autonomic neuropathy in type I and II
      diabetic patients and with history of myocardial infarction in type I diabetic
      patients, independently of time related variables.

PMID- 9014586
TI  - Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid.
AB  - OBJECTIVE: To demonstrate directly that highly reactive hydroxyl radicals (OH.)
      can be generated in patients with rheumatoid arthritis and contribute to joint
      damage, and to examine the ability of blood to cause OH. generation. METHODS: The
      sensitive and specific technique of hydroxylation of aromatic compounds
      (salicylate and phenylalanine) was used to measure OH.. Synovial fluid and blood
      from patients with active rheumatoid arthritis were aspirated and immediately
      added to tubes containing salicylate and phenylalanine as detectors of OH., or to
      tubes containing saline as a control. Levels of specific products of attack of
      OH. upon salicylate (2,3- and 2,5-dihydroxybenzoates) and phenylalanine (ortho-
      and meta-tyrosines) were measured by high performance liquid chromatography.
      RESULTS: Synovial fluid samples aspirated into saline never contained ortho- or
      meta-tyrosines or 2,3-dihydroxybenzoate. Of 53 patients examined, synovial fluid
      and blood from 36 caused formation of ortho- and meta-tyrosines when aspirated
      into solutions containing phenylalanine. Repeated sampling from three "positive"
      patients showed consistent evidence of these hydroxylation products. Similarly,
      of 22 patients examined, synovial fluid and blood from 18 caused formation of 2,3
      and 2,5-dihydroxybenzoates when aspirated into salicylate solutions. Further
      evidence for the role of OH. was provided by inhibition of the hydroxylation by
      the specific OH. scavengers mannitol and sodium formate. CONCLUSIONS: Aspirated
      knee joint fluids and blood from rheumatoid arthritis patients can generate OH.,
      consistent with current views on the importance of this radical as a cytotoxic
      agent in rheumatoid disease. The ability of body fluids to cause OH. formation is
      not correlated with simple laboratory indices of disease activity, but is
      reproducible on sequential sampling from the same patients. The mechanism and
      significance of the phenomenon in rheumatoid arthritis pathology remain to be
      established.

PMID- 9014587
TI  - Enthesopathy and tendinopathy in gout: computed tomographic assessment.
AB  - OBJECTIVE: To establish if computed tomography (CT) imaging, which has proved
      helpful in detecting intra-articular tophi in gout, can also be used to document
      gouty enthesopathy and tendinopathy. METHODS: Three patients with tophaceous gout
      and clinical involvement of the Achilles tendon (two cases) or patellar tendon
      (one case) were assessed with CT examination and plain radiographs. RESULTS: In
      the first two cases, CT images revealed linear or nodular high attenuation
      opacities within the substance of the Achilles tendons and their calcaneal
      insertion. In case 3, dense linear opacities were seen within the patellar tendon
      and within its tibial insertion. No such opacities of the tendons and entheses
      were seen on standard radiographs of these patients. CONCLUSIONS: CT appears to
      be the imaging method of choice for demonstrating monosodium urate deposits in
      entheses and tendons in tophaceous gout.

PMID- 9014588
TI  - Polymorphisms of the TAP1 and TAP2 transporter genes in Japanese SLE.
AB  - OBJECTIVE: To determine how polymorphism of transporter associated with antigen
      processing 1 and 2 (TAP1 and 2) alleles contributed to the pathogenesis of
      systemic lupus erythematosus (SLE) in Japanese patients. METHODS: TAP1 and TAP2
      typing was carried out in 52 Japanese patients with SLE and 95 normal subjects by
      the PCR-RFLP (restriction fragment length polymorphism) method. HLA-DR typing and
      HLA-DRB1*15 genotyping were carried out by the PCR method and PCR-SSCP (single
      stranded DNA conformation polymorphism) method, respectively. RESULTS: No
      particular TAP 1 allele was associated with Japanese SLE or with immunological
      subgroup of SLE. TAP2H showed a tendency towards increased frequency in SLE (5.8%
      v 0% in control), but the corrected P value was not significant. No other
      particular association of TAP2 allele was observed. Furthermore, these was no
      evidence for linkage disequilibrium between any TAP1/TAP2 alleles and HLA
      DRB1*1501--which is reported to be weakly but significantly association with
      Japanese SLE--in either the normal control or the SLE patient group. CONCLUSIONS:
      Neither the TAP1 nor the TAP2 gene appears to determine disease susceptibility to
      SLE in Japanese, and these results are in keeping with those reported in
      Caucasian SLE patients.

PMID- 9014589
TI  - Von Willebrand factor in the outcome of temporal arteritis.
AB  - OBJECTIVE: To determine fluctuation in circulating von Willebrand factor (vWF) in
      the outcome of patients with temporal arteritis. METHODS: Plasma vWF antigen
      concentrations were measured in 65 patients with biopsy proven temporal arteritis
      at different disease activity stages, in 12 with isolated polymyalgia rheumatica,
      and in 16 controls. Fourteen temporal arteritis patients underwent serial
      determinations during the course of their disease. RESULTS: vWF concentrations
      were significantly raised in temporal arteritis (mean 220 [arbitrary units],
      range 96 to 720) and in polymyalgia rheumatica (mean 196, range 103 to 266)
      compared with healthy controls (mean 98, range 75 to 137) (P < 0.05). Although
      vWF values tended to be higher in temporal arteritis, no significant differences
      were found between temporal arteritis and polymyalgia rheumatica patients nor
      between temporal arteritis patients with ischaemic complications (mean 269, range
      130 to 720) and those who presented with polymyalgia rheumatica or constitutional
      symptoms only (mean 179, range 140 to 220). The highest levels were obtained in
      patients with associated, mainly infectious, diseases (mean 631, range 240 to
      1680). Raised vWF values found in active temporal arteritis patients (mean 220,
      range 96 to 720) persisted within the first two years after the beginning of
      treatment (mean 244, range 102 to 510) but tended to normalise in patients in
      long term remission (mean 143, range 50 to 260). CONCLUSIONS: Persistent
      elevation of vWF during early remission of temporal arteritis might represent an
      endothelial activation status induced by a remaining inflammatory
      microenvironment rather than a marker of endothelial cell injury. In long term
      remission, decreasing vWF concentrations might reflect progression of
      inflammatory lesions to a healing stage.

PMID- 9014590
TI  - Screening for pain in knee osteoarthritis: which question?
AB  - OBJECTIVE: To compare three questions on knee pain with respect to determined
      prevalence and associations with disability and structural change. METHODS:
      Postal survey to 4057 men and women aged 40-79 years. Knee pain was defined by
      three questions: (A) "Have you ever had pain in or around the knee on most days
      for at least a month? If so, have you experienced any pain during the last year?"
      (B) "Have you had pain within the last year in or around the knee that occurred
      on most days for at least a month?" (C) "Have you had knee pain on most days of
      the last month?" [American College of Rheumatology (ACR) criteria for knee
      osteoarthritis]. Disability was assessed with the SF-36 health status
      questionnaire. Radiographs (AP weight bearing and skyline) were obtained on a
      proportion (n = 459) and graded for maximum osteophyte in any compartment.
      RESULTS: Prevalence of knee pain for questions A, B, and C were 28.3%, 25.3%, and
      19.3% respectively. Highest rates of disability were observed for question C
      (71.3% compared with 60.9% for question A). There was no major difference between
      questions in terms of percentage with > or = grade 1 osteophyte or > or = grade 2
      osteophyte. Sensitivity and specificity of each question for > or = grade 1
      osteophyte did vary, with question A being most sensitive but least specific
      (58.7% and 59.1%) and question C most specific (72.7%) but least sensitive
      (45.4%). CONCLUSIONS: Estimates of knee pain and disability are influenced by
      even minor changes in question content. The ACR criteria question may be a better
      predictor of disability but is relatively insensitive for use in the community.

PMID- 9014592
TI  - Should patients with recent onset of rheumatoid arthritis be offered genetic
      screening?

PMID- 9014591
TI  - Relation between fractional urate excretion and serum triglyceride
      concentrations.

PMID- 9014593
TI  - Serum and synovial fluid levels of interleukin-5 in a patient with eosinophilic
      fasciitis.

PMID- 9014594
TI  - Incidence of hepatitis induced by non-steroidal anti-inflammatory drugs (NSAID)

PMID- 9014595
TI  - Future prospects for evidence-based child health.

PMID- 9014596
TI  - Integrated management of childhood infections and malnutrition: a global
      initiative.

PMID- 9014597
TI  - Head lice in schoolchildren.

PMID- 9014598
TI  - Nutrient intakes and impact of fortified breakfast cereals in schoolchildren.
AB  - OBJECTIVE: To report micronutrient intakes in Northern Ireland schoolchildren,
      and to establish the contribution of fortified breakfast cereal to overall
      nutrient intakes and achievement of current dietary recommendations. DESIGN:
      Analysis of dietary intakes and physical characteristics of participants in a
      randomly selected 2% population sample of 1015 schoolchildren aged 12 and 15
      years in Northern Ireland during the 1990/1 school year. MAIN OUTCOME MEASURES:
      Dietary intakes, physical characteristics, and their association with consumption
      of fortified breakfast cereal. RESULTS: Mean micronutrient intakes were generally
      adequate with the exception of low intakes of folate (boys and girls) and iron
      (girls). Fortified breakfast cereals, consumed by a high proportion (94% boys;
      83% girls) of the sample, were associated with higher daily intakes of most
      micronutrients and fibre and with a macronutrient profile consistent with current
      nutritional recommendations. Appreciable proportions of subjects who did not
      consume fortified breakfast cereals had daily intakes that fell below the lower
      reference nutrient intake for riboflavin, niacin, folate, vitamin B-12, and iron
      (girls). CONCLUSIONS: The results demonstrate the potential of fortification in
      contributing to micronutrient intakes of schoolchildren, particularly where
      requirements are high, or for those on marginal diets of low nutritional quality.

PMID- 9014599
TI  - Dexamethasone and bacterial meningitis in Pakistan.
AB  - The objective of this study was to assess, in a developing country setting, the
      effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective
      double blind placebo controlled trial was conducted in 89 children aged from 2
      months to 12 years suffering from bacterial meningitis. Neurological,
      developmental, and hearing assessments were conducted at one, four, and 12 months
      after discharge. Forty eight patients received dexamethasone and 41 placebo.
      Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all
      patients at the time of admission the mean duration of illness was 5.7 days; 47%
      had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%)
      patients died. The mortality for the dexamethasone group was 25% as compared with
      12% in the group receiving placebo. Presentation to the hospital after four days
      of symptoms and with impaired conscious state were independent predictors of
      death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and
      42.3% had hearing impairment, whereas in the placebo group it was 24% and 30%
      respectively. Altered state of consciousness was a predictor of neurological
      sequelae. The presence of neurological sequelae and high cerebrospinal fluid
      protein independently predicted hearing loss. No beneficial effect of
      dexamethasone was observed on morbidity or mortality of this group of patients
      with bacterial meningitis. Dexamethasone is therefore not useful in developing
      countries as adjunctive treatment in patients seriously ill with bacterial
      meningitis, who present late for treatment and have been partially treated.

PMID- 9014601
TI  - Epogam evening primrose oil treatment in atopic dermatitis and asthma.
AB  - Essential fatty acids are claimed to have positive effects in atopic diseases. In
      a double blind, placebo controlled, parallel group study 58 out of 60 children,
      with atopic dermatitis and the need for regular treatment with topical skin
      steroids, completed a 16 weeks' treatment period with either Epogam evening
      primrose oil or placebo capsules. Twenty two of these subjects also had asthma.
      The parents used diaries to record symptom scores and concomitant medication.
      Peak expiratory flow was measured and disease activity was monitored by the
      clinician every four weeks. The plasma concentrations of essential fatty acids
      increased significantly in the group treated with Epogam capsules. The study
      demonstrated significant improvements of the eczema symptoms but no significant
      difference was found between the placebo and the Epogam groups. No therapeutic
      effect was shown on asthma symptoms or fidget.

PMID- 9014600
TI  - Clinical significance of cough and wheeze in the diagnosis of asthma.
AB  - OBJECTIVES: (1) To determine the prevalence of cough, wheeze, and breathlessness,
      both as single symptoms and in combination, in primary schoolchildren and their
      relation to doctor diagnosed asthma. (2) To identify in areas with different
      levels of dust pollution whether questionnaire reported 'cough alone' (without
      wheeze or breathlessness) had similar risk factors to the questionnaire reported
      triad of 'cough, wheeze, and breathlessness'. SUBJECTS AND METHODS: Two cross
      sectional community surveys of primary schoolchildren (5-11 years) were performed
      in 1991 and 1993. Parent completed questionnaires related to socioeconomic and
      respiratory factors were distributed through 15 schools in three areas of
      Merseyside, one of which had a relatively high level of dust pollution. Data were
      analysed to determine the prevalence of different respiratory symptom patterns.
      Univariate and multiple logistic regressions were used to investigate the
      associations between respiratory symptom profiles and potential risk factors.
      RESULTS: The proportions of completed questionnaires that were returned were
      similarly high in both surveys, 92% in 1991 (1872 of 2035) and 87% in 1993 (3746
      of 4288). The proportions of children with different respiratory symptom patterns
      were similar in the two surveys: in 1991, asymptomatic children 70.1% (1109 of
      1583), those with cough alone 8.9% (141 of 1583), and children with the symptom
      triad of cough, wheeze, and breathlessness 8.3% (132 of 1583); the figures for
      1993 were 69.5% (2144 of 3083), 9.2% (284 of 3083), and 7.3% (224 of 3083)
      respectively. The prevalence of doctor diagnosed asthma increased from 17.4% in
      1991 to 22.1% in 1993. The symptom of cough alone was associated with going to
      school in an area of increased air pollution. The symptom triad of cough, wheeze,
      and breathlessness was associated with reported allergies, familial history of
      atopy and preterm birth. In 1991, of children with the symptom of cough alone one
      in eight were diagnosed asthmatic; twice as many doctors made the diagnosis on
      this basis in 1993. CONCLUSION: The respiratory symptom of cough alone and cough,
      wheeze, and breathlessness represent clinical responses to different specific
      risk factors. Cough alone was associated with the environmental factors of school
      in the dust exposed zone and dampness in the home, whereas cough, wheeze, and
      breathlessness related to allergic history and preterm birth, and may be the best
      surrogate of asthma. Diagnosis of asthma on the basis of cough alone partly
      explains the increased prevalence of doctor diagnosed asthma, especially in dust
      polluted areas.

PMID- 9014602
TI  - Relationship between disease severity and inflammatory markers in cystic
      fibrosis.
AB  - To evaluate the clinical use of measuring neutrophil, lymphocyte, and eosinophil
      activities, serum myeloperoxidase (MPO), soluble interleukin-2 receptors (sIL
      2R), and eosinophil cationic protein (ECP) were measured in 98 patients with
      cystic fibrosis and in 85 healthy children. Serum concentrations of MPO, sIL-2R,
      and ECP were increased in patients with cystic fibrosis (median 807 micrograms/l,
      4452 pg/ml, 48.8 micrograms/l, respectively) compared with the controls (median
      319 micrograms/l, 2743 pg/ml, 9.4 micrograms/l). ECP concentrations, but not
      serum MPO or sIL-2R, were significantly related to disease severity assessed by
      the Shwachman-Kulczycki score and by pulmonary function (forced expiratory volume
      in one second % predicted). Neither ECP nor sIL-2R was influenced by Pseudomonas
      aeruginosa infection, acute pulmonary exacerbation, or atopy. Serum MPO, however,
      was strongly correlated with acute pulmonary exacerbation. In the light of these
      findings the measurement of serum ECP might thus be used for clinical monitoring
      and for assessing disease severity in cystic fibrosis. The measurement of serum
      MPO and sIL-2R did not correlate with the disease severity.

PMID- 9014603
TI  - Risk factors for liver rejection: evidence to suggest enhanced allograft
      tolerance in infancy.
AB  - After liver transplantation, a relatively low intensity immunosuppressive regimen
      is employed in our unit: after initial triple therapy (prednisolone,
      azathioprine, cyclosporin), prednisolone is discontinued at three months and
      azathioprine at one year. A retrospective study was therefore performed to
      determine the incidence of rejection, and to identify risk factors for rejection
      in our patient population. Over a 10 year period, 135 transplants were performed
      on 109 children. Thirty four (25%) were on infants less than 1 year old.
      Incidences of acute rejection and irreversible chronic rejection were calculated
      for grafts surviving more than one and four weeks respectively. Acute rejection
      occurred in 51 of 101 allografts (50%), and irreversible chronic rejection in 11
      of 91 allografts (12%). The immunosuppression strategy was not associated with an
      increased incidence of rejection. Acute rejection occurred in only eight of 28
      allografts (29%) in those transplanted during their first year, compared with 43
      of 73 (59%) in older children. Logistic and Cox regression analysis supported age
      at transplantation as a significant risk factor for acute rejection. Irreversible
      chronic rejection did not occur in any of 24 grafts in patients transplanted
      before one year, compared with 11 of 67 (16%) in older recipients. This suggests
      possible enhanced allograft tolerance with transplantation during the first year
      of life. This unexpected and potentially important finding now requires
      confirmation in other large patient series, with blind interpretation of post
      transplant liver biopsies.

PMID- 9014604
TI  - Circulating adhesion molecules ICAM-1, E-selectin, and von Willebrand factor in
      Henoch-Schonlein purpura.
AB  - Adhesion molecules play an important part in leucocyte transendothelial migration
      and thus may provide a useful marker of surface expression at inflammatory sites.
      In 20 patients with Henoch-Schonlein purpura serum intercellular adhesion
      molecule 1 (ICAM-1), E-selectin, and plasma von Willebrand factor (vWF) were
      determined by ELISA during the active and inactive phase of the disease. Twelve
      healthy children were studied as a control group. Serum ICAM-1 concentrations
      increased during the active phase of the disease and differed significantly
      compared with the inactive phase (p < 0.05). However ICAM-1 in the active phase
      did not differ significantly compared with controls (p = 0.08). Serum E-selectin
      concentrations did not differ in the active and inactive phase of the disease. By
      contrast, vWF increased in the active phase of the disease and differed
      significantly compared with inactive disease and control groups (p < 0.01).
      Considering the adhesion molecules and vWF, only vWF correlated well with the C
      reactive protein measurement in the active phase, which is considered a good
      marker of disease activity. These data suggest that plasma vWF is a good marker
      of vascular inflammation and endothelial damage. Circulating ICAM-1 might be an
      additional parameter in some of the patients.

PMID- 9014606
TI  - Outcome of children born to epileptic mothers treated with carbamazepine during
      pregnancy.
AB  - AIM: The purpose of the study was to assess whether there was an increased rate
      of congenital anomalies or significant developmental delay in infants of women
      with epilepsy who had been treated with carbamazepine during pregnancy. METHODS:
      47 children were studied, aged 6 months-6 years, who were born to 37 epileptic
      mothers on carbamazepine monotherapy (group A). All children had a complete
      physical and neurodevelopmental assessment by a developmental paediatrician, and
      41 a complete psychological evaluation. They were compared with 47 children of
      similar socioeconomic status (group B). RESULTS: Six of the 47 children in group
      A had typical facial features of 'carbamazepine syndrome'. The average cognitive
      score of children in group A was significantly lower than in group B. This was
      mainly because all six children with carbamazepine syndrome had a development
      quotient or intelligence quotient below 90. There were no differences between the
      two groups in physical growth or in the rate of major anomalies. Two children in
      group A had cleft palate but in each case this was found in a parent as well.
      CONCLUSIONS: In utero exposure to carbamazepine may result in 'carbamazepine
      syndrome' characterised by facial dysmorphic features and mild mental
      retardation. Prevalence of carbamazepine syndrome does not seem to be related to
      the dose of carbamazepine or the presence of maternal convulsions. It may depend
      upon heredofamilial factors that have yet to be defined. One possible factor is
      decreased activity of the enzyme epoxide hydrolase with resulting increased
      concentrations of carbamazepine epoxide which may be teratogenic.

PMID- 9014605
TI  - Lichen sclerosus et atrophicus and sexual abuse.
AB  - AIMS: The aetiology of lichen sclerosus et atrophicus (LSA) is unknown. A series
      of 42 cases of this uncommon condition is reported. The aim of this study was to
      identify associations of LSA and document the association with sexual abuse.
      METHODS: Information about the patients was obtained by retrospective case note
      review and some patients were contacted by telephone for further information.
      RESULTS: In 12 cases there was evidence of sexual abuse. The abused group were
      slightly older than the non-abused group but were similar in all other respects.
      All three patients who presented over the age of 12 years had evidence of sexual
      abuse. Genital trauma was recalled by the patient or found at examination in 17
      cases. Evidence of autoimmunity was present in five cases. Positive
      microbiological isolates were obtained in 18 cases. In only 11 cases were there
      no associated factors. The symptoms of LSA started between the ages of 3 and 7
      years in most patients. The usual symptoms were related to genital skin
      involvement, and symptoms related to bladder and bowel function were common
      (50%). CONCLUSION: In this large series of paediatric LSA, associations with
      trauma, autoimmunity, and infection were noted. There was a high rate of
      coexisting sexual abuse with LSA, possibly due to genital trauma.

PMID- 9014607
TI  - Body size and subcutaneous fat patterning in adolescence.
AB  - Factors that influence low birth weight at term may also be associated with
      subcutaneous fat patterning in later life. This hypothesis was investigated in a
      comparative (retrospective) cohort study. The subjects, born in Cardiff between
      1975 and 1977, were of mean age 15.7 years. Cases (low birth weight (< 2500 g) at
      term) were matched with controls (normal birth weight (3000-3800 g) at term) for
      sex, parity, place of birth, date of birth, and gestation. Subscapular skinfold
      (an index of central subcutaneous fat) and triceps skinfold (an index of
      peripheral subcutaneous fat) were measured using a Holtain skinfold caliper. The
      differences (cases minus controls) (95% confidence interval) for subscapular and
      triceps skinfolds were respectively -0.3 mm (-1.74 to 1.14) and -0.48 mm (-1.75
      to 0.79). These findings are inconsistent with the hypothesis that low birth
      weight at term is associated with subcutaneous fat patterning in adolescence.

PMID- 9014609
TI  - Child health statistical review, 1996.
AB  - There is much evidence that the children born in the last decade of the 20th
      century are healthier and living longer than children born earlier this century,
      and that children born too small or too soon are now more likely to reach
      adulthood than similar children born 10 or 20 years ago. Yet measures of social
      disadvantage (poverty, underachievement in education, lone parenthood) are
      increasing, putting this generation of children at higher risk of morbidity later
      in life.

PMID- 9014608
TI  - Rickets and soil strontium.
AB  - The subjects of this study were children aged 6-60 months living in villages in
      the Ulas Health Region, Sivas. The villages were divided into two groups
      according to the amount of strontium in the soil: region 1, > 350 ppm, 650
      children; region 2, < 350 ppm, 1596 children. Overall, the prevalence of one or
      more clinical signs of rickets was 22.9%. The prevalence in region 1 was 31.5%
      and that in region 2, 19.5%. These values were significantly different (p <
      0.001). When other variables which may be relevant to the occurrence of rickets
      were taken into account, the difference in prevalence persisted. The results
      suggest that in villages where nutrition is mainly based on grain cereals the
      presence of strontium in the soil will increase the prevalence of rickets
      significantly. As a preventive measure, a greater proportion of the foods given
      to children in these villages should be derived from animal origin, and cereals
      and drinking water supplies should be obtained from villages with a low soil
      strontium content, or calcium supplements should be given.

PMID- 9014610
TI  - Are we 'fit for the future' now?

PMID- 9014611
TI  - Donald Court: man of vision (1912-94).

PMID- 9014612
TI  - Use of the colposcope in examination for sexual abuse.

PMID- 9014613
TI  - N1303K mutation and diabetes mellitus in cystic fibrosis.

PMID- 9014614
TI  - Secondary cases of meningococcal disease.

PMID- 9014615
TI  - Diphtheria: are we ready for it?

PMID- 9014616
TI  - Non-steroidal anti-inflammatory drugs may predispose to invasive group A
      streptococcal infections.

PMID- 9014617
TI  - HIV related Kaposi's sarcoma.

PMID- 9014618
TI  - Ether anaesthesia comes to London. December 1846.

PMID- 9014619
TI  - Is it always necessary to antagonize residual neuromuscular block? Do children
      differ from adults?

PMID- 9014620
TI  - Dose-response relationships for neostigmine antagonism of rocuronium-induced
      neuromuscular block in children and adults.
AB  - Dose-response relationships for the antagonism of intermediate-acting
      neuromuscular blocking agents have not been evaluated previously in children. We
      have examined the dose-response relationships for neostigmine antagonism of 90%
      rocuronium-induced neuromuscular block in children and adults, during nitrous
      oxide-1 MAC of isoflurane anaesthesia. We studied 40 children, aged 2-10 yr, and
      50 adults, aged 18-60 yr; all received a single bolus dose of rocuronium 0.6 mg
      kg-1 and accelerometry was used to monitor neuromuscular transmission. When the
      first twitch of the train-of-four (TOF) response (T1) recovered to 10% of its
      control (T0), one of five doses of neostigmine 0, 5, 10, 20 or 50 micrograms kg-1
      was given by random allocation to each of the study groups (n = 8 children and n
      = 10 adults). Recovery of T1 and TOF ratio (T4/T1%) was recorded for 10 min after
      initial administration of neostigmine. Onset time of rocuronium-induced block was
      faster in children than in adults (mean 64.6 (95% confidence intervals 57.7-71.5)
      s vs 83.7 (70.7-96.6) s; P < 0.05). The time to 10% recovery of T1/T0 was shorter
      in children than in adults (25.4 (22.9-27.9) min vs 38.8 (36.1-41.4) min; P <
      0.001). Spontaneous and antagonist-assisted recovery were more rapid in children
      than in adults. Adequate recovery (T4/T1 of 80%) occurred in children at 4, 5 and
      8 min after neostigmine 50, 20 and 10 micrograms kg-1, respectively. Adequate
      recovery was not produced in adults by any dose of neostigmine within 10 min. The
      effective doses of neostigmine required to achieve a TOF ratio of 80% (ED80)
      after 10 min in children and adults were, respectively, 7.10 (5.2-9.8) micrograms
      kg-1 and 56.56 (45.5-71.9) micrograms kg-1 (P < 0.001). There was no advantage in
      administering doses of neostigmine greater than 20 micrograms kg-1 to antagonize
      90% rocuronium-induced neuromuscular block in children. In contrast, it appeared
      prudent to use neostigmine 50 micrograms kg-1 or more for adequate antagonism of
      a similar degree of block in adults.

PMID- 9014621
TI  - Comparison of the effects of mivacurium on the diaphragm and geniohyoid muscles.
AB  - Although subjects often report difficulty with swallowing shortly after receiving
      neuromuscular blocking agents, difficulty with swallowing during recovery from
      neuromuscular blocking agents appears to be infrequent. We have used
      electromyography to compare onset and recovery at the diaphragm and geniohyoid
      airway muscles after an intubating dose of mivacurium (0.2 mg kg-1) to determine
      if the geniohyoid muscles were particularly sensitive to neuromuscular blocking
      agents. Twelve adults undergoing elective surgery were anaesthetized with
      propofol and fentanyl and the trachea intubated without neuromuscular blocking
      agents. The left hypoglossal and right phrenic nerves were stimulated with
      percutaneous needle electrodes and the electromyogram recorded with surface
      electrodes. EMG responses were measured after a bolus dose of mivacurium 0.2 mg
      kg-1. Recordings were also made of the mechanical response of the adductor
      pollicis to supramaximal ulnar nerve stimulation. There was no difference in the
      rate of onset of block for geniohyoid muscles and the diaphragm, but recovery to
      25% and 90% of the control response was shorter at the diaphragm (median 14.5
      (95% confidence limits 12.9-15.3) min and 23.8 (21.7-26) min) than at the
      geniohyoid muscle (19.4 (15.6-20.1) min and 29.2 (26.3-31.4) min), respectively
      (P < 0.05). When the train-of-four ratio of the mechanical response of the thumb
      reached 70%, the diaphragm and geniohyoid muscles had recovered completely in all
      patients.

PMID- 9014622
TI  - Concentration-related effects of propofol on the auditory evoked response.
AB  - We have studied the effects of propofol, as the sole agent, at blood
      concentrations of 1-10 micrograms ml-1, on the first 100 ms of the auditory
      evoked response (AER) in 41 women before gynaecological surgery. AER were
      recorded with the patients awake and then after 30 min of one of seven stepped
      infusion regimens. Each patient was studied at only one blood concentration. The
      recordings were edited and processed off-line by coherent signal averaging, to
      obtain reliable estimates of each AER. We measured standard features, such as
      amplitudes and latencies of brainstem wave V and the mid-latency waves Na, Pa and
      Nb. In addition, we studied several composite indices, intended to give a more
      global characterization of the AER. We derived relationships between the doses
      and blood concentrations of propofol, features of the AER and response to eyelash
      stimulus and venepuncture. Nb latency was better than either concentration or
      dose rate of propofol in providing a confident explanation of the likelihood of
      eyelash response (which parallels the response to command). A cut-off value of 53
      ms had a sensitivity of 100%, a specificity of 96% and an overall correctness of
      98% as a discriminator of eyelash response vs no response. Several alternative
      AER-derived indices provided more than 90% correctness in discrimination, as did
      a dose rate of propofol of 6.3-7.8 mg kg-1 h-1 or a blood concentration of 2.9
      micrograms ml-1. We conclude that the concentration and dose of propofol were
      good discriminators of response to venepuncture, while the latency of the Na wave
      was the most successful of the AER features.

PMID- 9014623
TI  - Comparison of patient-controlled sedation with either methohexitone or propofol.
AB  - We studied 42 patients undergoing oral surgery under local anaesthesia with i.v.
      sedation, allocated randomly to receive either methohexitone (group M) or
      propofol (group P) for patient-controlled sedation (PCS). Group M patients self
      administered 2.5-mg (0.5 ml) bolus doses of methohexitone and group P, 5-mg (0.5
      ml) doses of propofol, without a lockout. The 0.5-ml bolus dose was delivered
      over 7.2 s for both drugs. The procedure was completed satisfactorily in all
      patients. Patients in both groups achieved their desired levels of sedation. No
      patient lost verbal contact. Group M patients had higher heart rates during the
      procedure. The lowest SpO2 values recorded were 92% and 95% for group P and group
      M, respectively. Immediately after operation patients in group M reported that
      they felt more sleepy than those in group P (P < 0.01) but there were no
      differences at subsequent times. The results of the psychomotor tests were
      comparable for the two groups after operation, except for the "posting box task"
      at 15 min after operation when the mean decrement (compared with preoperative
      performance) was -3% for group P and -13% for group M (P < 0.05). More patients
      in group P complained of pain in their hand. We conclude that methohexitone is a
      suitable alternative drug to propofol for PCS.

PMID- 9014624
TI  - Local anaesthesia to the airway reduces sedation requirements in patients
      undergoing artificial ventilation.
AB  - Patients in the intensive care unit require large doses of sedative/analgesic
      drugs to tolerate the presence of a tracheal tube and other unpleasant stimuli.
      The ideal regimen for sedatives and analgesics has not yet been found. We have
      investigated the effects of topical local anaesthesia to the pharynx and airway
      on sedative/analgesic requirements in 30 ICU patients (25-75 yr old) with no
      obvious brain injury, undergoing mechanical ventilation. Oral tracheal tubes were
      changed to a modified tube which allowed instillation of local anaesthetic
      solutions onto the pharyngeal, laryngeal and tracheal mucosa. Lignocaine 1% (5
      ml) or 5 ml of 0.9% saline were instilled hourly for 12 h each for a total of 24
      h, in a double-blind, randomized crossover design. Baseline sedation was
      maintained with propofol or alfentanil infusions, or both, which were titrated to
      patient comfort and to maintain an optimum sedation score throughout. Twenty-five
      patients completed the study. Mean total propofol and alfentanil requirements
      were 766 (SD 524) mg and 17 (7.6) mg, respectively, during 12 h of lignocaine
      instillation, and 1321 (862) mg and 25 (11.4) mg, respectively, during 12 h of
      saline instillation. There was a significant reduction (P < 0.05) in the
      requirements for both agents during the period of lignocaine instillation.

PMID- 9014625
TI  - Comparative effects of thiopentone and propofol on respiratory resistance after
      tracheal intubation.
AB  - To compare the effects of propofol and thiopentone on tracheal intubation-induced
      bronchoconstriction, 37 patients were allocated randomly to anaesthesia with
      either thiopentone 4 mg kg-1 followed by a 15-mg kg-1 h-1 continuous infusion or
      propofol 3 mg kg-1 followed by a 9-mg kg-1 h-1 continuous infusion. Intubation
      was facilitated by vecuronium 0.1-0.2 mg kg-1. Respiratory system resistance
      (Rrs) was measured by a CP-100 pulmonary function monitor, 5 min after
      intubation. The 5-min post-intubation Rrs values were significantly lower in the
      propofol group (8.5 (SD 1.5) cm H2O litre-1 S-1) than in the thiopentone group
      (10.9 (3.2) cm H2O litre-1 S-1). Thirty minutes after commencing isoflurane
      nitrous oxide anaesthesia, Rrs declined by 17.5 (SEM 3.6)% from baseline in the
      thiopentone group, but by only 1.6 (2.6)% in the propofol group. We conclude that
      the dose of propofol administered provided more protection against tracheal
      intubation-induced bronchoconstriction than an induction dose of thiopentone.

PMID- 9014626
TI  - Propofol or halothane anaesthesia for children with asthma: effects on
      respiratory mechanics.
AB  - Propofol may cause histamine release and alter airway tone and reactivity.
      Although its use has been reported to be safe in asthmatics, there is a lack of
      information on its effect on lung function in children with asthma. We measured
      respiratory mechanics after i.v. or inhalation anaesthesia in 60 children, aged 2
      12 yr, with or without asthma. Anaesthesia was induced with propofol 3 mg kg-1,
      fentanyl 1 microgram kg-1 and atracurium 0.5 mg kg-1 and maintained with an
      infusion of propofol 10 mg kg-1h-1 and 50% nitrous oxide in oxygen. Halothane was
      administered subsequently at a concentration of 1 MAC. Respiratory mechanics were
      measured by applying a single-compartment model using multi-linear regression
      analysis to calculate dynamic compliance (Crs,dyn) and respiratory system
      resistance (Rrs), based on: Pao = V/Crs,dyn + V Rrs + PA,EE, where Pao = airway
      opening pressure, PA,EE = alveolar pressure, V = volume and V = flow. The two
      groups were comparable in age, weight and ventilation variables (tidal volume and
      peak pressure). Respiratory mechanics during propofol anaesthesia were comparable
      in normal and asthmatic children (Rrs = 20.5 X 10(-4) (SD 5.2 X 10(-4)) vs 21.5 X
      10(-4) (5.7 X 10(-4)) kPa ml-1 S-1 (ns) and Crs,dyn = 247.5 (76.51 vs 235.1
      (63.8) ml kPa-1 (ns)). Halothane produced a minimal decrease in Rrs and a minimal
      increase in tidal volume in both groups without changes in Crs,dyn. In
      conclusion, respiratory mechanics were comparable after propofol anaesthesia in
      both children with and without asthma. Changes in Rrs after halothane
      administration were not clinically relevant.

PMID- 9014627
TI  - Hepatocellular integrity during and after isoflurane and halothane anaesthesia in
      surgical patients.
AB  - Subclinical disturbance in hepatocellular integrity, indicated by glutathione
      transferase Alpha (GSTA), has been associated with halothane, sevoflurane and
      propofol, but not with isoflurane anaesthesia. We anaesthetized 82 patients with
      isoflurane or halothane at 1 MAC for superficial surgery. GSTA concentration were
      measured with a sensitive time-resolved immunofluorometric assay in serum
      samples. GSTA concentrations increased from a baseline value of geometric mean
      1.8 micrograms litre-1 (95% confidence intervals 1.4-2.2 micrograms litre-1) to a
      peak of 4.3 (3.3-5.7) micrograms litre-1 in the isoflurane group and from 2.1
      (1.6-2.9) micrograms litre-1 to 6.2 (4.1-9.5) micrograms litre-1 in the halothane
      group. The change in GSTA was significant within groups but the difference
      between groups was not significant. Two patients exhibited an unexpectedly large
      increase in GSTA (peaks 370 and 620 micrograms litre-1) and a mild increase in
      alanine aminotransferase after halothane anaesthesia. We conclude that
      hepatocellular integrity was mildly disturbed after isoflurane and halothane
      anaesthesia but there was no difference between anaesthetics. Halothane
      anaesthesia may be associated with more advanced hepatocellular disturbance in
      some cases.

PMID- 9014628
TI  - Standardization of non-invasive impedance cardiography for assessment of stroke
      volume: comparison with thermodilution.
AB  - Since its introduction by Kubicek and colleagues, impedance cardiography has been
      suggested as a non-invasive, simple, safe and cost-effective method of measuring
      stroke volume. Several controversial reports on its validity have been published.
      Pitfalls of this method included the nature of the electrode system and the
      validity of the equations. Therefore, the purpose of this study was to compare
      two different spot electrode arrays and the two most frequently used stroke
      volume equations with each other and with thermodilution. In 37 patients, 24-36 h
      after cardiac surgery, we performed simultaneous measurements of stroke volume
      with impedance cardiography (SVIC) and with thermodilution (SVTD). SVIC was
      obtained using the lateral spot (LS) electrode array, according to Bernstein, and
      a newly proposed modified semi-circular (MSC) spot electrode array. The equations
      of Kubicek and Sramek-Bernstein were used to calculate SVIC. The Sramek-Bernstein
      equation was valid only when the LS array was used; the Kubicek equation
      determined SVTD correctly only when the MSC array was used. However, a
      considerably better correlation and agreement (mean difference (2 SD)) was found
      between SVIC and SVTD for the latter (r = 0.90, 0.5 (17.1) ml vs r = 0.64, -4.9
      (31.8) ml for the Sramek-Bernstein equation). We conclude that the most valid
      measurement of stroke volume using impedance cardiography was obtained when the
      MSC array was used together with Kubicek's equation.

PMID- 9014629
TI  - Lack of specific renal haemodynamic effects of different doses of dopamine after
      infrarenal aortic surgery.
AB  - Dopamine is administered frequently in the operating theatre and intensive care
      unit patients undergoing mechanical ventilation with the aim of specifically
      enhancing renal blood flow. In an uncontrolled, open study, we administered
      sequentially different doses of dopamine (0, 2, 4, 8 and 0 microgram kg-1 min-1)
      during a 1-h period each. Systemic haemodynamic and renal haemodynamic variables
      were measured simultaneously using a pulmonary artery catheter and
      radiopharmaceuticals, respectively. We studied seven haemodynamically stable
      patients (mean age 66 yr), with a serum creatinine concentration < 160 mumol
      litre-1, after elective infrarenal abdominal aortic reconstruction. All patients
      received extradural analgesia with bupivacaine and sufentanil, and none had a
      previous history of heart failure. Dopamine induced a dose-dependent increase in
      cardiac index which returned to baseline after cessation of the dopamine
      infusion. Glomerular filtration rate (GFR) increased with all doses of dopamine,
      whereas renal blood flow (RBF) increased significantly only with the 2- and 4
      microgram kg-1 min-1 doses. However, the ratio RBF/cardiac output remained
      unchanged with the 2- and 4-microgram kg-1 min-1 doses, but decreased with 8
      micrograms kg-1 min-1 from 14 (1.5)% to 10 (1.3)%. We conclude that dopamine
      increased RBF and GFR as a result of an increase in cardiac output.

PMID- 9014630
TI  - Antinociception by intrathecal midazolam involves endogenous neurotransmitters
      acting at spinal cord delta opioid receptors.
AB  - Intrathecal midazolam causes antinociception by combining with spinal cord
      benzodiazepine receptors. This effect is reversible with doses of naloxone,
      suggesting involvement of spinal kappa or delta but not mu opioid receptors. The
      antinociceptive effects of intrathecally administered drugs in the spinal cord
      were demonstrated by measurements of the electrical current threshold for
      avoidance behaviour in rats with chronically implanted lumbar intrathecal
      catheters. A comparison was made of suppression by two opioid selective
      antagonists (nor-binaltorphimine (kappa selective) and naltrindole (delta
      selective)) of spinal antinociception caused by equipotent doses of opioids
      selective for different receptor subtypes (U-50488H (kappa), DSLET and DSBULET
      (delta), fentanyl (mu)) and the benzodiazepine midazolam. Nor-binaltorphimine
      selectively suppressed the effects of U-50488H but not midazolam or fentanyl.
      However, the delta selective antagonist, naltrindole, caused dose-related
      suppression of antinociception produced by both delta opioid agonists and
      midazolam with the same ED50 (0.5 nmol). We conclude that intrathecal midazolam
      caused spinally mediated antinociception in rats by a mechanism involving delta
      opioid receptor activation.

PMID- 9014631
TI  - A model of the first pass passage of drugs from i.v. injection site to the heart-
      parameter estimates for lignocaine in the sheep.
AB  - A general model, based on indicator dilution principles, of the initial
      distribution and effects of drugs in a target organ after i.v. bolus
      administration is presented. The model was validated from previous studies of
      myocardial pharmacokinetics and pharmacodynamics of lignocaine in sheep. It is
      proposed that i.v. drug injection produces a concentration "peak" of drug in
      venous blood, which is attenuated by vascular mixing, and lung and heart
      kinetics, as the drug is transported from the injection site to the heart where
      it exerts its effects. The model predicted that the first passage of this peak
      through the heart was the principal component of myocardial concentrations of
      lignocaine for 10 min after injection before recirculation became important.
      Injection rate, cardiac output and myocardial blood flow were important
      determinants of the magnitude of the first pass peak. The model provides a
      physiological framework for analysing the initial distribution of drugs.

PMID- 9014633
TI  - Effect of halothane, isoflurane and desflurane on lower oesophageal sphincter
      tone.
AB  - We have studied the effects of volatile anaesthetics on lower oesophageal
      sphincter (LOS) tone in three groups of eight pigs allocated randomly to receive
      end-tidal concentrations of 0.5, 1.0 and 1.5 MAC of desflurane, isoflurane or
      halothane for 15 min. LOS and oesophageal barrier pressures (BrP = LOSP - gastric
      pressure) were measured using a manometric method. The decrease in BrP paralleled
      the decrease in LOS pressure and was significant at 0.5 MAC for isoflurane and at
      1.0 MAC for halothane. At 1.5 MAC, BrP values were approximately 62% of baseline
      values for halothane, 37% for isoflurane and 83% for desflurane. Inter-group
      comparisons showed that BrP did not differ at baseline and at 0.5 MAC. At 1.0 MAC
      the effect of isoflurane on BrP was significantly different from desflurane (P <
      0.001) and halothane (P < 0.02) whereas the effect of desflurane on BrP was not
      significantly different from halothane. At 1.5 MAC the effect of isoflurane on
      BrP was significantly different from desflurane (P < 0.01) and halothane (P <
      0.05) whereas the effect of desflurane on BrP was not significantly different
      from halothane. We conclude that desflurane maintained BrP and this may be
      clinically important in patients at high risk of regurgitation.

PMID- 9014632
TI  - Measurement of cardiac output by transoesophageal Doppler echocardiography in
      anaesthetized horses: comparison with thermodilution.
AB  - In order to determine if transoesophageal Doppler echocardiography could be used
      to estimate cardiac output in anaesthetized horses, we have compared the
      technique with estimations of cardiac output by thermodilution in eight healthy
      adult thoroughbreds. Measurements of aortic blood flow velocity were made by high
      pulse repetition frequency (HPRF) and continuous wave (CW) Doppler
      echocardiography from a 3.5-MHz transoesophageal probe. Cardiac output was
      increased during the study by administration of dobutamine, providing a range of
      cardiac output measurements by thermodilution from 15.0 to 64.4 liter min-1.
      Estimations derived from CW Doppler overestimated cardiac output compared with
      thermodilution (bias = 4.0 litre min-1). Estimations from HPRF Doppler
      echocardiography more closely reflected measurements obtained by thermodilution
      (bias = 0.7 litre min-1). Limits of agreement between the techniques were similar
      for both modes of insonation (HPRF = -7.7 to 9.1 litre min-1, CW = -4.9 to 12.8
      litre min-1). There were significant differences in bias between both Doppler
      techniques and thermodilution for individual horses. As a result, for any
      individual horse, limits of agreement between the techniques were closer (HPRF =
      +/- 6.4 litre min-1, CW = +/- 7.6 litre min-1). We conclude that transoesophageal
      echocardiography provided an alternative, effective and non-invasive method for
      measurement of cardiac output in anaesthetized horses.

PMID- 9014634
TI  - Distinguishing cerebrospinal fluid from saline used to identify the extradural
      space.
AB  - Because of the potential seriousness of unrecognized dural puncture during the
      performance of extradural analgesia and the widespread use of normal saline for
      the "loss of resistance" technique, it is important to differentiate between
      cerebrospinal fluid (CSF) and saline dripping from the extradural needle. During
      insertion of lumbar drains in 10 neurosurgical patients, we first identified the
      extradural space using saline for loss of resistance. Temperature (using the back
      of the gloved hand), pH, glucose and protein (using urine testing sticks) were
      tested by a blinded observer for ability to distinguish saline aspirated from the
      extradural space from CSF aspirated on establishing the dural puncture.
      Temperature, glucose and protein were independently 100% accurate in
      distinguishing saline from CSF. One saline sample had a pH value greater than 7
      compared with nine CSF samples. We conclude that simple bedside testing for
      temperature, glucose, protein and pH accurately distinguished between CSF and
      saline used to identify the extradural space.

PMID- 9014636
TI  - A modification of sub-mental intubation.
AB  - In patients who have sustained base of skull fractures, the mode of intubation is
      controversial, with many anaesthetists arguing against nasal intubation. In
      several maxillofacial procedures temporary intermaxillary fixation (IMF) in the
      intraoperative period may be essential to achieve optimal results in fixation.
      For patients with combined facial and base of skull injury, tracheotomy may have
      to be performed. The submental approach to intubation allows IMF to be used
      without resort to nasal intubation or tracheotomy. We describe a modification of
      the original technique which is applicable to any reinforced tracheal tube and
      which does not compromise the airway.

PMID- 9014635
TI  - Use of a pneumatic tourniquet induces changes in central temperature.
AB  - Twenty-six patients requiring orthopaedic surgery were anaesthetized and
      oesophageal and rectal temperature were monitored continuously. Twenty patients
      requiring a pneumatic tourniquet were allocated prospectively to one of two
      groups: passive group (Pg) with reflective insulation on all available skin
      surface (n = 10) and forced group (Fg), with active warming by a forced air
      system (n = 10). Six patients without a tourniquet were used as a reference group
      (Rg). The pneumatic tourniquet time was similar in the tourniquet groups. During
      tourniquet inflation, oesophageal temperature increased with time. The difference
      was significant compared with the reference group at approximately 20 min. At
      about 30 min, oesophageal temperature in group Fg was significantly higher than
      that in group Pg. After tourniquet deflation, temperature decreased transiently.
      Changes in rectal temperature were similar but delayed significantly. A mechanism
      to explain the increase in core temperature during pneumatic tourniquet use
      remains unclear. A redistribution mechanism by cooling of the blood in a cold and
      vasodilated limb could explain the decrease of temperature after tourniquet
      deflation.

PMID- 9014637
TI  - Hepatic rupture complicating eclampsia in pregnancy.
AB  - We describe hepatic rupture in a 37-yr-old woman admitted to the intensive care
      unit after an eclamptic convulsion. The intensive care and surgical management
      are discussed.

PMID- 9014638
TI  - Tolerance of laparoscopy for resection of phaeochromocytoma.
AB  - We describe two patients who underwent resection of phaeochromocytoma by a
      laparoscopic approach. Although outcome from surgery was successful, there was
      marked variability in hormonal and haemodynamic changes. In one patient, despite
      an infusion of nicardipine, peritoneal insufflation produced a marked increase in
      catecholamine concentrations associated with transient but intense
      vasoconstriction, but there was no change in the second patient. In both
      patients, exsufflation caused no significant haemodynamic changes in spite of the
      high doses of nicardipine given throughout the procedures.

PMID- 9014639
TI  - Randomization is important in studies with pain outcomes: systematic review of
      transcutaneous electrical nerve stimulation in acute postoperative pain.
AB  - We set out to examine the evidence for the importance of randomization of
      transcutaneous electrical nerve stimulation (TENS) in acute postoperative pain.
      Controlled studies were sought; randomization and analgesic and adverse effect
      outcomes were summarized. Forty-six reports were identified by searching
      strategies. Seventeen reports with 786 patients could be regarded unequivocally
      as randomized controlled trials (RCT) in acute postoperative pain. No meta
      analysis was possible. In 15 of 17 RCT, we judged there to be no benefit of TENS
      compared with placebo. Of the 29 excluded trials, 19 had pain outcomes but were
      not RCT; in 17 of these 19 TENS studies, the authors concluded that TENS had a
      positive analgesic effect. No adverse effects were reported. Non-randomized
      studies overestimated treatment effects.

PMID- 9014640
TI  - Unexpected high spinal block in obstetrics.

PMID- 9014641
TI  - Fuzzy logic control of inspired volatile anaesthetic concentrations.

PMID- 9014642
TI  - Is Doppler monitoring mandatory in laparoscopic surgery?

PMID- 9014643
TI  - Hypotension during subarachnoid anaesthesia.

PMID- 9014644
TI  - Haemodilution induces a hypercoagulable state.

PMID- 9014645
TI  - Haemodynamic and neuroendocrine responses after pneumoperitoneum during
      cholecystectomy.

PMID- 9014646
TI  - Glycine absorption and hypocalcaemia.

PMID- 9014647
TI  - Locating an arterial foreign body by ultrasonography.

PMID- 9014648
TI  - Energy expenditure and physical activity in subjects consuming full-or reduced
      fat products as part of their normal diet.
AB  - It has been suggested that energy expenditure is higher in subjects consuming
      reduced-fat, high-carbohydrate diets than in subjects consuming full-fat, low
      carbohydrate diets. In a 6-month randomized, controlled trial, seventeen women
      and twenty men (age 20-35 years; BMI 22-28 kg/m2) had free access either to a
      range of about forty-five reduced-fat products or the full-fat equivalents. At
      the end of the 6 months, energy intake, sleeping metabolic rate (SMR), average
      daily metabolic rate (ADMR), and physical activity (AO) were measured. The
      intervention resulted in a mean difference of the change of the fat content of
      the diet of 6% of energy (P < 0.01) between the two groups. SMR. ADMR and AO were
      virtually the same in both groups. The results suggest that the change in fat
      content of the diet has no effect on physical activity and energy expenditure.
      However, subjects with a higher activity level consumed more carbohydrate
      (ADMR/SMR: r = 0.49, P < 0.01: AO: r = 0.57, P < 0.001).

PMID- 9014649
TI  - Substrates available for colonic fermentation from oat, barley and wheat bread
      diets. A study in ileostomy subjects.
AB  - Nutrients not absorbed in the small bowel will form substrates for microbial
      growth in the colon which may have implication for the development of colon
      cancer. The aim of the present study was to investigate whether fibre-rich oat
      and barley diets increase the excretion of energy-supplying nutrients from the
      small bowel compared with a low-fibre wheat diet, and whether a possible increase
      could be related to the beta-glucan content. Nine ileostomy subjects were served
      four types of bread together with a low-fibre basal diet (12 g dietary fibre/d).
      The breads were based on either wheat flour (W diet, 7 g dietary fibre/d), oat
      bran (OB diet, 29 g dietary fibre/d), the same amount of oat bran with addition
      of beta-glucanase (EC 3.2.1.4) (OBE diet, 19 g dietary fibre/d) or a fibre-rich
      barley fraction (B diet, 35 g dietary fibre/d). An increased ileal excretion of
      starch was observed with the barley diet but no effect of the oat beta-glucan on
      starch recovery was found. The NSP + Klason lignin in the ileostomy effluents
      accounted only for 24, 31, 24 and 35% of the gross energy excretion in the W, OB,
      OBE and B diet periods respectively. A large part of the dry weight and energy
      (30, 21, 28 and 27%, in the W, OB, OBE and B diets respectively) in the effluents
      could not be identified as fat, protein, total starch or NSP + Klason lignin.
      This unidentified part was probably made up of oligosaccharides, endogenous
      losses and nutrient complexes. Methods for identifying and analysing these
      components should be developed and their role as substrates for colonic
      fermentation and colon cancer development ought to be investigated.

PMID- 9014650
TI  - Vitamin A and carotenoid status in rural China.
AB  - Vitamin A status of 260 groups of twenty-five males or twenty-five females, aged
      35-64 years, surveyed in twenty-four provinces of the People's Republic of China,
      was assessed by measuring plasma retinol. retinol-binding protein and beta
      carotene concentrations. Direct measurements of food intake over a 3 d period and
      questionnaire data on the frequency of consumption of vegetables, fruits, animal
      products and other dietary items were also used. Vitamin A status appeared to be
      low only in specific counties but in general was satisfactory or only marginally
      deficient. Plasma beta-carotene levels were strikingly low in comparison with
      Western levels despite generous vegetable consumption suggesting that intake of
      vitamin A precursors may have been adequate but not abundant enough to maintain
      high circulating plasma levels of beta-carotene. Plasma beta-carotene, for both
      males and females, was significantly correlated with the frequency of consumption
      of green vegetables. Plasma retinol, for males, was highly correlated with meat,
      fish, oil and alcohol consumption expressed both in quantity or frequency of
      consumption. Higher levels of plasma retinol, together with lower levels of
      plasma beta-carotene in males compared with females, suggest that men consume
      more animal products or may have higher retinol requirements and therefore a
      higher rate of conversion of beta-carotene to retinol.

PMID- 9014651
TI  - The effect of long-term calcium supplementation on indices of iron, zinc and
      magnesium status in lactating Gambian women.
AB  - The effect of long-term supplementation with CaCO3 on indices of Fe, Zn and Mg
      status was investigated in a randomized, double-blind intervention study of sixty
      lactating Gambian women. The supplement contained 1000 mg Ca and was consumed
      between meals 5 d/week, for 1 year starting 1.5 weeks postpartum. Compliance was
      100%. Plasma ferritin concentration, plasma Zn concentration and urinary Mg
      output were measured before, during and after supplementation at 1.5, 13, 52 and
      78 weeks postpartum. No significant differences in mineral status were observed
      at any time between women in the supplement and placebo groups. Analysis of the
      longitudinal data series showed that plasma ferritin and Mg excretion were
      characteristic of the individual (P < 0.001). Within individuals, ferritin
      concentration was higher at 1.5 weeks postpartum than later in lactation (P =
      0.002). Plasma Zn concentration was lower at 1.5 weeks postpartum than at other
      times (P < 0.001), an effect which disappeared after albumin correction. Low
      plasma concentrations of ferritin and Zn indicated that the Gambian women were at
      high risk of Fe and Zn deficiency. Measurements of alpha 1-antichymotrypsin
      suggested that the results were not confounded by acute-phase responses. The
      results of the present study indicate that 1000 mg Ca as CaCO3 given between
      meals does not deleteriously affect plasma ferritin and Zn concentrations or
      urinary Mg excretion in women who are at risk of Fe and Zn deficiency.

PMID- 9014652
TI  - Application of agar-fill method to estimate compartment capacity of
      gastrointestinal tract in Syrian hamsters (Mesocricetus auretus).
AB  - In the present study we have developed the agar-fill method for the measurement
      of gastrointestinal-tract capacity (GTC) to replace the in vitro water-fill
      method. This would estimate GTC without using complex equipment and techniques,
      and can be applied to the measurement of GTC for small laboratory animals. We
      attempted to confirm the efficiency of the agar-fill method by investigating the
      relationship between dietary neutral-detergent fibre (NDF) content and GTC. The
      digestion trials were carried out using the Syrian hamster (Mesocricetus
      auretus). The trials were conducted using both sexes, two age-groups and three
      levels of dietary NDF with a cross-classified design. The size of each
      gastrointestinal organ was determined as tissue weight (TW) and GTC. The DM
      intake, digestible DM intake, DM digestibility, NDF digestibility, acid-detergent
      fibre (ADF) digestibility and digesta transit time were also measured. GTC
      increased with increasing NDF content of the diets. TW responded similarly to
      increasing NDF content, but the response was smaller than that of GTC. DM
      digestibility decreased with increasing NDF content of the diet. The digestible
      DM intake did not decrease with increasing NDF because DM intake increased with
      NDF content. Digesta transit time was not shorter of the high-NDF diet group but
      DM intake increased with increasing NDF content. NDF digestibility did not differ
      significantly between low- and medium-NDF diets. ADF digestibility was low in the
      low-NDF-diet group. The digestion characteristics were highly correlated with TW
      and GTC, except for TW of small intestine. These correlations were higher with
      GTC than with TW. The results of the present study confirm previous findings
      suggesting that the agar-fill method is a useful means of estimating GTC for
      small laboratory animals.

PMID- 9014654
TI  - Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus
      faecalis on cholesterol metabolism in rats fed on a fat- and cholesterol-enriched
      diet.
AB  - The effect of a mixture of organisms (a probiotic mixture) comprising Bacillus,
      Lactobacillus, Streptococcus, Clostridium, Saccharomyces and Candida (10(7-8)
      colony-forming units/g rice bran of each component) on lipid metabolism was
      compared with that of L. acidophilus and that of S. faecalis. There were four
      treatment groups: rice bran (control), the mixture of organisms, L. acidophilus
      or S. faecalis (30 g/kg) were given to rats in a fat- and cholesterol-enriched
      diet for 4 weeks. The serum total cholesterol concentration of the group fed on
      the mixture of organisms was reduced by 15-33% compared with the other groups at
      the end of the 4-week feeding period (P < 0.05). This group also had a lower
      hepatic cholesterol concentration (36-44%) than the two single-bacteria groups (P
      < 0.05). 3-Hydroxy-3-methylglutaryl-Co A reductase (NADPH; EC 1.1.1.34)
      activities of the mixed-organism and L. acidophilus groups were significantly
      lower (61-63%) than those of the other groups (P < 0.05); the activity of the S.
      faecalis group was also significantly lower (42%) than that of the control group
      (P < 0.05). The faecal cholesterol and bile acid concentrations of the mixed
      organism group increased compared with those of the L. acidophilus and S.
      faecalis groups (P < 0.05). The capacity of the mixed-organism cells to bind bile
      salt in vitro was significantly higher (approximately 50%) than that of the
      single-bacteria cells (P < 0.05). On the other hand, cholesterol micelle
      formation for the mixed-organism cells was significantly (approximately 9%) lower
      than that of the single-bacteria cells (P < 0.05). These results indicate that
      the mixture of organisms decreased the synthesis of cholesterol in the liver and
      increased the loss of steroids from the intestine, in rats. Thus, the mixture of
      organisms had a hypocholesterolaemic role.

PMID- 9014653
TI  - Role of thyroid hormones in early postnatal development of skeletal muscle and
      its implications for undernutrition.
AB  - Energy intake profoundly influences many endocrine axes which in turn play a
      central role in development. The specific influence of a short period of mild
      hypothyroidism, similar to that induced by undernutrition, in regulating muscle
      development has been assessed in a large mammal during early postnatal life.
      Hypothyroidism was induced by providing methimazole and iopanoic acid in the feed
      of piglets between 4 and 14 d of age, and controls were pair-fed to the energy
      intake of their hypothyroid littermates. Thyroid status was evaluated, and
      myofibre differentiation and cation pump concentrations were then assessed in the
      following functionally distinct muscles: longissimus dorsi (l. dorsi), soleus and
      rhomboideus. Reductions in plasma concentrations of thyroxine (T4; 32%, P <
      0.01), triiodothyronine (T3; 48%, P < 0.001), free T3 (58%, P < 0.001) and
      hepatic 5'-monodeiodinase (EC 1.11.1.8) activity (74%, P < 0.001) occurred with
      treatment. Small, although significant, increases in the proportion of type I
      slow-twitch oxidative fibres occurred with mild hypothyroidism, in l. dorsi (2%,
      P < 0.01) and soleus (7%, P < 0.01). Nuclear T3-receptor concentration in l.
      dorsi of hypothyroid animals compared with controls increased by 46% (P < 0.001),
      a response that may represent a homeostatic mechanism making muscle more
      sensitive to low levels of circulating thyroid hormones. Nevertheless, Na+, K(+)
      ATPase (EC 3.6.1.37) concentration was reduced by 15-16% in all muscles (l. dorsi
      P < 0.05, soleus P < 0.001, rhomboideus P < 0.05), and Ca(2+)-ATPase (EC
      3.6.1.38) concentration was significantly reduced in the two slow-twitch muscles:
      by 22% in rhomboideus (P < 0.001) and 23% in soleus (P < 0.05). It is concluded
      that during early postnatal development of large mammals a period of mild
      hypothyroidism, comparable with that found during undernutrition, induces changes
      in myofibre differentiation and a down-regulation of cation pumps in skeletal
      muscle. Such changes would result in slowness of movement and muscle weakness,
      and also reduce ATP hydrolysis with a concomitant improvement in energetic
      efficiency.

PMID- 9014656
TI  - Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose
      in rats.
AB  - Dietary supplementation with oligofructose (OFS; 100 g/kg), a non-digestible
      oligomer of beta-D-fructose, decreases serum triacylglycerols in serum and VLDL
      of rats. In order to investigate the role of hepatic metabolism in the
      hypolipidaemic effect of OFS, male Wistar rats were fed on a standard diet with
      or without 100 g Raftilose P95/kg as OFS source for 30 d. OFS feeding (1)
      significantly decreased triacylglycerol and phospholipid concentrations in both
      blood and liver, (2) increased the glycerol-3-phosphate liver content but
      decreased the hepatic activity of glycerol-3-phosphate acyltransferase (EC
      2.3.1.15), suggesting a decrease in acylglycerol synthesis, (3) did not affect
      the blood non-esterified fatty acid concentrations, but (4) reduced by 54% the
      capacity of isolated hepatocytes to synthesize and secrete triacylglycerols from
      labelled acetate; the activity of fatty acid synthase, a key lipogenic enzyme was
      also significantly decreased. These findings suggest that OFS decreases serum
      triacylglycerols by reducing de novo fatty acid synthesis in the liver; the lower
      insulin level in the serum of OFS-fed rats could explain, at least partly, the
      metabolic effect induced by such non-digestible carbohydrates.

PMID- 9014657
TI  - Streptozotocin-induced diabetes lowers retinol-binding protein and transthyretin
      concentrations in rats.
AB  - Retinol-binding protein (RBP) and transthyretin (TTR) in the plasma, liver and
      kidney, retinol in plasma, and total vitamin A in the liver were measured in rats
      6 weeks after diabetes mellitus had been induced by streptozotocin (STZ). The
      diabetic rats gained 83% less weight despite consuming 45% more feed than the non
      diabetic controls. Plasma and kidney concentrations of RBP and TTR were
      significantly lower in diabetic than in the non-diabetic control rats. Unlike the
      retinol carrier proteins, plasma albumin concentrations remained unaffected.
      Plasma concentrations of retinol were decreased while its hepatic levels
      increased in the diabetic animals. The depressed circulatory levels of retinol
      may reflect an altered metabolism of its transport proteins.

PMID- 9014655
TI  - Olive oil and rapeseed oil differ in their effect on plasma low-density
      lipoprotein metabolism in the guinea-pig.
AB  - The effects of olive oil and rapeseed oil, two different high-oleic-acid oils, on
      plasma LDL and hepatic cholesterol metabolism were compared in guinea-pigs.
      Animals were fed on semipurified diet containing 150 g fat/kg as either olive oil
      (OL), rapeseed oil plus 100 g palm oil/kg (C-P) or olive oil plus 350 g
      safflowerseed oil/kg (OL-S). Olive oil was enriched with safflowerseed oil (OL-S
      diet) to increase linoleic acid and to decrease palmitic acid concentrations, in
      order to evaluate whether differences in plasma LDL concentrations were due to
      intrinsic effects of the specific oil (rapeseed or olive oil) or to differences
      in the content of specific fatty acids. No differences due to dietary fat source
      were found in plasma total and HDL-cholesterol levels or in LDL composition.
      Plasma LDL-cholesterol levels were lower on the C-P diet than the OL diet (P <
      0.05) while plasma LDL-cholesterol levels in animals fed on the OL-S diet were
      not significantly different from either dietary group (P > 0.05). The number of
      hepatic apo B/E (LDL) receptors was on average 25% higher in animals fed on the C
      P diet compared with those fed on diets containing olive oil. Likewise, cardiac
      muscle lipoprotein lipase (EC 3.1.1.34) activity was significantly higher in the
      C-P group than in the OL and OL-S dietary groups. Dietary fat source had no
      effect on hepatic cholesterol levels or 3-hydroxy-3-methylglutaryl (HMG) CoA
      reductase (EC 1.1.1.34) activity. The results indicate that olive oil and
      rapeseed oil, both rich sources of monounsaturated fatty acids, differ in their
      effect on LDL metabolism in the guinea-pig.

PMID- 9014658
TI  - Diets deficient in selenium and vitamin E affect plasma lipoprotein and
      apolipoprotein concentrations in the rat.
AB  - The present study examined the effects of Se, vitamin E and combined Se and
      vitamin E deficiencies in rats on plasma lipid, lipoprotein and apolipoprotein
      (apo) concentrations. Deficiencies were induced by feeding rats the respective
      diets for 6 weeks. The study shows that Se deficiency results in increased
      concentrations of plasma cholesterol and apo E. Both could be explained by an
      increase in the HDL1 fraction. Vitamin E deficiency alone had no significant
      effect on plasma lipid, lipoprotein and apo concentrations. Se deficiency in
      combination with vitamin E deficiency leads to an increase in plasma LDL and apo
      B concentrations. These results point to the need for further investigations on
      the mechanism by which Se deficiency affects lipoprotein metabolism.

PMID- 9014659
TI  - Copper homeostasis in rats fed on a high-sulphide diet.
AB  - The mechanism underlying the reduced Cu status in rats fed on a high-sulphide
      diet was investigated. Male rats aged 6 weeks were fed ad libitum on purified
      diets containing either 0 or 500 mg S2-/kg and demineralized water for a period
      of 2 weeks. The high-sulphide diet had no effect on feed intake, body-weight gain
      or weight of liver and kidney but significantly reduced Cu concentrations in
      plasma and kidney. Biliary Cu excretion was decreased significantly in rats fed
      on the high-sulphide diet. Apparent Cu absorption (Cu intake-faecal Cu) and true
      Cu absorption (Cu intake-(faecal Cu-biliary Cu)) were significantly lowered after
      sulphide feeding for 2 weeks. Rats fed on the high-sulphide diet excreted less Cu
      in urine than did the controls. We conclude that high sulphide intake reduces Cu
      status in rats through inhibition of Cu absorption which is reflected by a
      decrease in biliary Cu excretion as a secondary feature.

PMID- 9014660
TI  - Technique of hepatectomy.

PMID- 9014661
TI  - Desmoids in familial adenomatous polyposis.
AB  - Clinical desmoid disease affect approximately 10 per cent of patients with
      familial adenomatous polyposis (FAP); the subclinical rate is unknown. Desmoids
      are probably neoplastic rather than regenerative in origin and may arise in
      association with germline or somatic mutations at or beyond codon 1444 of the APC
      gene. Intra-abdominal desmoids behave unpredictably but are an important cause of
      death in those with FAP. Signal intensity on magnetic resonance imaging reflects
      tumour cellularity, which in part determines progression, and this may help
      management. Surgical treatment of advanced desmoids is hazardous, but medical
      treatments have limited success. Chemotherapy with doxorubicin and dacarbazine is
      currently under evaluation.

PMID- 9014662
TI  - Abdominal wounds in war.
AB  - The reported mortality rate associated with abdominal wounds sustained in war
      varies considerably because of the heterogeneity of wounds and the different
      circumstances under which figures have been collected rather than different
      treatment strategies. This review draws together a personal experience, reports
      from ten wars, and information from a database for war wounded into an analysis
      of abdominal wounds. The analysis attempts to bring understanding to why people
      die with abdominal wounds in war and so clarifies logistic and treatment issues.

PMID- 9014663
TI  - Laparoscopic ultrasonography during cholecystectomy.
AB  - The routine use of intraoperative cholangiography during cholecystectomy has been
      debated extensively. Intraoperative ultrasonography was a quick, efficient
      alternative in open cholecystectomy. A prospective controlled trial to evaluate
      its usefulness in laparoscopic cholecystectomy is reported. Two groups of 100
      patients each were examined during operation with laparoscopic ultrasonography
      and intraoperative cholangiography. In the first group an adapted urethral probe
      was used and in the second group a new specialized laparoscopic probe.
      Intraoperative cholangiography followed immediately after laparoscopic
      ultrasonography in each patient. In group 1 bile duct stones (n = 4) were
      detected with a sensitivity of 100 and 75 per cent, a specificity of 98 and 99
      per cent, and an overall accuracy of 98 per cent for both ultrasonography and
      cholangiography. In group 2, 11 patients demonstrated common duct calculi. The
      sensitivity, specificity and overall accuracy for laparoscopic ultrasonography
      and intraoperative cholangiography were 91 and 64 per cent, 100 and 100 per cent,
      and 99 and 96 per cent respectively. The differences between groups 1 and 2 and
      between ultrasonography and cholangiography were not significant. Variations in
      the anatomy of the bile duct were observed in 21 patients in group 1 by
      laparoscopic ultrasonography and in 20 by intraoperative cholangiography. In
      group 2, 64 variations were demonstrated in 50 individuals by ultrasonography and
      61 variations in 47 patients by cholangiography. Vascular variations were seen
      with ultrasonography in 22 and 24 patients in groups 1 and 2 respectively. In
      conclusion, laparoscopic ultrasonography (with either probe) proved as accurate
      as intraoperative cholangiography in detecting bile duct stones, and the
      specialized probe detected significantly more variations of the bile duct than
      the adapted probe.

PMID- 9014664
TI  - A western surgical experience of peripheral cholangiocarcinoma.
AB  - The aim of this retrospective study was to analyse outcome in 31 European
      patients operated on for peripheral cholangiocarcinoma between 1988 and 1995
      (hilar cholangiocarcinoma was excluded). Before 1992, in addition to conventional
      resection, patients with irresectable tumour and with no extrahepatic metastasis
      underwent total hepatectomy with liver transplantation. Mild abdominal pain was
      the most frequent presenting clinical sign (11 of 31 patients) and jaundice was
      present in only four patients. Preoperative histological findings were available
      for 20 patients but the diagnosis was correct in only eight of these. Nineteen
      patients had curative surgery: 17 underwent conventional resection and two had
      total hepatectomy with liver transplantation. Major hepatectomy was performed in
      12 of 17 cases, extended to the caudate lobe in five, to the bile duct confluence
      in four and to the retrohepatic vena cava in one. Postoperative mortality and
      morbidity rates were three and seven of 19 patients respectively, median survival
      was 15 months, and actuarial 1-, 2- and 5-year survival rates were 67, 40 and 32
      per cent respectively. Twelve patients had only exploratory laparotomy because of
      the presence of extrahepatic metastasis or irresectable tumour. The invasive
      nature of peripheral cholangiocarcinoma can explain the limited number of
      resectable cases and the particularly unfavourable prognosis. Total hepatectomy
      does not provide survival benefit. Conventional surgery remains the only
      effective treatment, even for patients with advanced stage tumours.

PMID- 9014665
TI  - Surgery for biliary obstruction by tumour thrombus in primary liver cancer.
AB  - Five patients with primary liver cancer presented with obstructive jaundice due
      to extension of tumour thrombus into the biliary ducts. Three patients had
      hepatocellular carcinoma, two of whom had alcoholic cirrhosis, and the other two
      had a peripheral cholangiocarcinoma. Preoperative diagnosis of biliary thrombus
      was best achieved by ultrasonography and computed tomography which showed
      peripheral hepatic tumour with dilated bile ducts containing dense material. All
      patients underwent liver resection associated with biliary exploration, clearance
      and T-tube drainage. Major hepatectomy was required in four cases. There were no
      postoperative deaths; one patient developed a subphrenic collection of bile which
      was drained percutaneously. All patients survived more than a year; median
      survival was 29 months. There are two long-term survivors without recurrence at
      29 and 80 months. Patients with primary liver cancer and jaundice due to migrated
      tumour fragments in the common bile duct may benefit from surgical resection
      which can result in long-term resolution of symptoms and occasional cure.

PMID- 9014666
TI  - One hundred and fifty hepatic resections: evolution of technique towards
      bloodless surgery.
AB  - A technique of hepatic resection is described and the results of 150 resections
      are reviewed. Hepatic transection was performed, under intermittent portal inflow
      occlusion, using ultrasonic aspiration to skeletonize portal branches and venous
      tributaries. Control of venous haemorrhage during resection was optimized by
      argon beam coagulation and lowering central venous pressure to between 0 and 4
      cmH2O by extradural blockade and systemic nitroglycerine infusion. One patient
      with jaundice died in hospital, giving a mortality rate of 0.7 per cent. There
      were no deaths in patients without jaundice and cirrhosis. Fifteen patients (10.0
      per cent) had significant complications, nine medical and six surgical, including
      three bile leaks (2.0 per cent). Mean blood loss was 814 ml for the whole study
      but only 434 ml in the last 4 years. During this latter period mean blood
      transfusion in hospital was 0.5 units and mean postoperative haemoglobin value
      fell by 0.7 g per 100 ml. Hepatic resection can be performed with the same degree
      of confidence and similar low morbidity as any other major surgical procedure.

PMID- 9014667
TI  - Randomized comparison of the neuroendocrine response to laparoscopic
      cholecystectomy using either conventional or abdominal wall lift techniques.
AB  - Increase in plasma renin activity and noradrenaline concentration occur in
      response to carbon dioxide insufflation during laparoscopic cholecystectomy. In a
      randomized study the conventional carbon dioxide pneumoperitoneum was compared
      with the abdominal wall lift method for laparoscopic cholecystectomy, with
      special reference to neuroendocrine changes and renal function. The total
      mean(s.d.) volume of carbon dioxide insufflated was 42(23) litres with the
      conventional method and 9(7) litres with abdominal wall lift (P < 0.001).
      Mean(s.d.) intra-abdominal pressure after 15 min of insufflation was 11(2) and
      3(9) mmHg respectively (P < 0.01). In the conventional group mean(s.d.) plasma
      renin activity increased slightly from 5.5(2.1) to 6.1(2.0) ng ml-1 during the
      first 55 min of laparoscopic cholecystectomy. In the abdominal wall lift group
      plasma renin activity decreased from 5.3(2.7) to 3.8(0.9) ng ml (P < 0.01 between
      the groups). Plasma antidiuretic hormone concentration increased similarly in
      both groups. Diuresis was significantly less with conventional pneumoperitoneum
      during the first 35 min of the operation compared with the abdominal wall lift
      method (P < 0.001). There were significant increases in plasma noradrenaline
      concentration in both groups (P < 0.001), but the increase was slightly higher in
      the conventional group during the first 15 min of insufflation. The abdominal
      wall lift method with minimal carbon dioxide insufflation was associated with
      smaller neuroendocrine responses and better preservation of renal function
      compared with conventional carbon dioxide pneumoperitoneum.

PMID- 9014668
TI  - Solitary caecal diverticulum strangulated in a femoral hernia.

PMID- 9014669
TI  - Comparison of the cost of preventing postoperative deep vein thrombosis with
      either unfractionated or low molecular weight heparin.
AB  - The relative costs were analysed of (1) no prophylaxis against deep vein
      thrombosis (DVT), (2) selective treatment of DVT after confirmation of diagnosis,
      (3) general prophylaxis with standard low-dose unfractionated heparin and (4)
      general prophylaxis with low molecular weight heparin (LMWH) in patients
      undergoing elective general abdominal surgery or elective hip surgery. The mean
      calculated costs per patient undergoing general abdominal surgery were: Swedish
      crowns (SEK) 1950 for no prophylaxis, SEK 5710 for selective treatment of DVT,
      SEK 735 for prophylaxis with unfractionated heparin and SEK 665 for prophylaxis
      with LMWH. The corresponding costs for hip surgery were SEK 3930, SEK 10790, SEK
      1730 and SEK 1390 respectively. Thus, the least expensive management strategy in
      patients undergoing elective general abdominal or hip surgery would appear to be
      general prophylaxis with either unfractionated heparin or LMWH. Furthermore,
      general prophylaxis with LMWH would appear to be more cost-effective than general
      prophylaxis with unfractionated heparin.

PMID- 9014670
TI  - Videoscopic subfascial incompetent perforator vein ablation.

PMID- 9014671
TI  - Knee-length versus thigh-length graduated compression stockings in the prevention
      of deep vein thrombosis.

PMID- 9014672
TI  - Pedal bypass for limb-threatening ischaemia: an 11-year review.
AB  - Fifty-six patients with limb-threatening ischaemia had pedal revascularization
      with either autologous vein (n = 39) or sequential composite graft with a 6-mm
      polytetrafluoroethylene prosthesis and autologous vein (n = 17); 75 per cent had
      gangrene and skin necrosis and 25 per cent had ischaemic rest pain alone. Twelve
      grafts occluded within the first week, and resulted in major amputation in eight
      patients after unsuccessful revision. Two patients required amputation for
      persistent ischaemia despite a patent bypass. One patient died from bowel
      perforation (2 per cent). In 47 (84 per cent) of the 56 patients limb and life
      were preserved. The primary patency rate after 1, 2 and 4 years was 65, 55 and 55
      per cent respectively, the secondary patency rate was 71, 62 and 62 per cent, and
      cumulative limb salvage rates were 77, 71 and 66 per cent. Life-table survival
      rates during follow-up (median 25 (range 0-112) months) were 89, 78 and 52 per
      cent respectively after 1, 2 and 4 years. Thirteen of 21 patients who died during
      follow-up did not require major amputation. Pedal reconstruction with autologous
      vein provides limb salvage until death in nearly two-thirds of patients with
      critical limb ischaemia resulting from crural arterial occlusive disease.

PMID- 9014673
TI  - Rectus sheath bupivacaine analgesia after aortic surgery.

PMID- 9014674
TI  - Prospective randomized trial comparing sequential avulsion with stripping of the
      long saphenous vein.
AB  - Eighty patients with primary varicose veins of the long saphenous system were
      randomized to have the long saphenous vein removed either by stripping to below
      the knee or by sequential avulsion. There was no difference between the two
      methods in the time taken to remove the vein. There was significantly more pain
      after stripping during the week following operation (P < 0.001). Median pain
      score after stripping was 5, reducing to 3 at 1 week, compared with 2, reducing
      to 1, for sequential avulsion. Median area of bruising measured at 1 week was 160
      (range 0-1800) cm2 for stripping and 56 (range 0-544) cm2 for sequential avulsion
      (P < 0.01). Sequential avulsion is less painful, reduces bruising and avoids a
      significant scar below the knee.

PMID- 9014675
TI  - Prospective randomized trial comparing postoperative pain and return to physical
      activity after transabdominal preperitoneal, total preperitoneal or Shouldice
      technique for inguinal hernia repair.
AB  - In a prospective randomized study postoperative pain, analgesic consumption,
      return to physical activity and work, cosmetic result and experience with the
      type of operation were assessed in 86 patients undergoing inguinal hernia repair
      by means of either the Shouldice technique (n = 34), the laparoscopic
      transabdominal preperitoneal (TAPP) (n = 28) or total preperitoneal (TPP) (n =
      24) repair. Patients having TAPP repair had decreased visual analogue scale
      scores for pain on the day of operation compared with those undergoing TPP and
      Shouldice repair (4.8 versus 6.5 and 6.2 respectively, P = 0.02) and on the first
      postoperative day compared with TPP (4.0 versus 6.0, P = 0.01). There was no
      difference between the three groups for days 2, 3, 4, 5 and 30 after operation.
      Patient satisfaction with the operation, analgesic consumption, return to
      physical activity such as walking, driving, climbing stairs, running, bicycling
      and sexual intercourse, as well as return to work, was comparable in the three
      groups. There was a better cosmetic result after TAPP and TPP repair. This study
      failed to demonstrate significant benefits from laparoscopic hernia repair over
      the Shouldice technique.

PMID- 9014676
TI  - Ethical implications of recognizing nutritional support as a medical therapy.

PMID- 9014678
TI  - Pouch-related fistula following restorative proctocolectomy.
AB  - Prognostic factors and outcome of pouch-related fistula were analysed from a
      series of 21 patients, 20 of whom had an ileal J pouch manually anastomosed to
      the dentate line following mucosectomy. Fistula occurred more often after pouch
      formation for ulcerative colitis than for familial adenomatous polyposis. In 6
      patients the fistula occurred more than 5 months after closure of the diverting
      loop ileostomy. The origin of the leak was the anastomosis in 14 patients, the
      vertical staple line in two and the end of the efferent limb in five. Nine forms
      of treatment were utilized and these were successful in 11 patients and
      unsuccessful in ten including three pouch excisions. Adverse prognostic factors
      were late fistula, the presence of an enterocutaneous or a pouch-vaginal fistula
      track, and diagnosed or suspected Crohn's disease. Resolution of the fistula
      followed none of six diverting loop ileostomies performed alone, three of 33
      attempted drainage procedures, four of ten direct closures, and four of five
      repeat ileal pouch-anal anastomoses. It is concluded that an aggressive
      therapeutic approach using repeat ileal pouch-anal anastomosis increases the
      success rate.

PMID- 9014677
TI  - Fast-to-slow muscle conversion by chronic electrostimulation: effects on
      mitochondrial respiratory chain function with possible implications for the
      gracilis neosphincter procedure.
AB  - The effects of chronic, around the clock, low-frequency electrostimulation on the
      respiratory chain activity and cytochrome content of freshly isolated
      mitochondria were evaluated in rabbit skeletal muscle before and after 30 days of
      continuous or cyclical electrostimulation using a totally implantable system and
      a training programme now used in humans. The respiratory activity measured in
      state III increased strongly after electrostimulation. The efficiency of the
      respiratory chain increased significantly after electrostimulation but the
      activity of complex [(reduced nicotinamide adenine dinucleotide dehydrogenase)
      did not increase. The amount of cytochromes a and a3, b562, and c and c1
      increased clearly after electrostimulation. The respiratory activity rate of
      mitochondria obtained after continuous electrostimulation was apparently higher
      than after cyclical electrostimulation. Chronic uninterrupted low-frequency
      electrostimulation, using a clinical training programme, induces an increase in
      mitochondrial respiratory chain activity in purified mitochondria of skeletal
      muscle. These changes are the basis of induced resistance to fatigue in fast-to
      slow muscle conversion by chronic electrostimulation.

PMID- 9014679
TI  - Results after restorative proctocolectomy and ileal pouch-anal anastomosis in
      patients with familial adenomatous polyposis and coexisting colorectal cancer.
AB  - Although the operation of choice for patients with familial adenomatous polyposis
      (FAP) is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA),
      its place in the management of patients with FAP and cancer has not been defined.
      The authors have reviewed their experience with these patients to determine the
      safety of IPAA and its efficacy as a cancer operation. The records of 55 patients
      with FAP who had undergone IPAA were examined. Follow-up studies included an
      annual questionnaire and physical examination. Eight patients had FAP with
      coexisting colorectal cancer. Median age at diagnosis was 25 (range 13-46) years,
      and at operation 33 (range 22-36) years. Of the eight patients (four men), four
      had colonic cancer and four had rectal cancer. Synchronous colorectal carcinoma
      was found in two patients. Staging according to the tumor node metastasis
      classification showed that five patients had stage 1 tumour, two had stage 2 and
      one had stage 3. Tumours were well, moderately or poorly differentiated in one,
      five and two patients respectively. During a median follow-up of 56 (range 14-98)
      months, metastasis developed in the liver of one patient 66 months after surgery.
      Two patients suffered complications: one had small bowel obstruction and the
      other mucosal prolapse. Tubular adenomas were found in the pouch of two patients
      and in the anal transitional zone of one. Pouch function is good to excellent in
      all surviving patients. Restorative proctocolectomy for patients with FAP and
      coexisting colorectal cancer can be undertaken with a favourable prognosis and
      function. It is compatible with curative intent.

PMID- 9014680
TI  - Resection of an end-colostomy stricture with a circular stapling device.

PMID- 9014681
TI  - Biomechanical stabilization of the nipple valve in continent ileostomy.
AB  - Despite stapler stabilization, sliding complication of nipple valve function
      occur in 19 per cent of continent ileostomies. Because the tendency of the ileum
      to desuscept is triggered by traction forces on the mesentery of the nipple
      during filling of the reservoir, a technique was developed to neutralize this
      biomechanical strain. In addition, to obtain fibrous healing between the muscular
      layers, the mucosa of contacting intestinal walls was removed by selective
      ultrasonic fragmentation. The valves of 18 consecutive patients were operated on
      with this technique. In six of these, a sliding valve was restabilized in a
      median time of 1.2 (range 0.4-2.9) years after conventional construction of the
      pouch. All are functioning well after a median of 4.6 (range 3.0-6.0) years.
      Between 1.8 and 4.8 years after operation a healed area between the musculature
      of the nipple and pouch of 4.5-7.2 cm2 was shown by endosonography. This
      procedure may provide long-term prevention of sliding complications in continent
      ileostomies.

PMID- 9014682
TI  - Problems in diagnosis and management of goitre in childhood and adolescence.
AB  - This study is a retrospective review of 17 patients aged 16 and under with a
      total of 18 goitres, who were investigated and treated at Bristol Children's
      Hospital and Bristol Royal Infirmary between 1967 and 1994. There were five
      neoplasms, comprising follicular adenoma (three) and papillary carcinoma (two).
      Other benign causes of goitre included nodular goitre (four), non-toxic
      hyperplasia (three) and chronic lymphocytic thyroiditis (three). The authors
      suggest some guidelines to help in the diagnosis and management of goitre in
      young patients, as a consequence of significant difficulties encountered in 12 of
      the 17 patients in this series.

PMID- 9014683
TI  - Reduced collagen accumulation after major surgery.
AB  - The preoperative and postoperative wound-healing capacity of 23 patients
      undergoing elective major abdominal, thoracic or urological surgery was tested
      objectively by the subcutaneous accumulation of hydroxyproline and proline in an
      expanded polytetrafluoroethylene (ePTFE) tube. Before scheduled surgery two ePTFE
      tubes were implanted for removal after 5 and 10 days. This was repeated for each
      patient immediately after surgery. After 10 days a higher amount of
      hydroxyproline was measured before than after operation (median 2.91 (range 0.37
      14.45) versus 1.45 (range 0.26-6.94) micrograms/cm, P = 0.01)). This decline was
      significantly higher in the six patients who had a postoperative infection
      (median 3.02 (range -0.06 to 6.14) versus 0.36 (range -1.56 to 12.60)
      micrograms/cm, P = 0.02). This study shows that major surgery is associated with
      impairment of subcutaneous collagen accumulation in a test wound, suggesting
      diminished systemic wound-healing capacity in such patients.

PMID- 9014684
TI  - D2 gastrectomy: lessons from a prospective audit of the learning curve.
AB  - A 3-year prospective study of the learning curve for D2 gastrectomy was carried
      out by one surgeon beginning to perform the operation independently after
      intensive specialist training. Some 38 patients were treated; there were four
      postoperative deaths and 22 patients had complications. Postoperative morbidity
      decreased significantly with time (rS = -0.38, P = 0.02, 95 per cent confidence
      interval -0.62 to -0.07). The physiological component of POSSUM (Physiological
      and Operative Severity Score for the enUmeration of Mortality and morbidity) was
      significantly lower in the third year (median value 15, 16 and 14 for years 1, 2
      and 3, n = 31, chi 2 = 7.5, 2 d.f., P = 0.02, Kruskal-Wallis test), but the
      operative POSSUM scores and the number of lymph nodes found were not decreased
      (median operative POSSUM score 19, 18 and 21, n = 31, chi 2 = 0.2, 2 d.f., P =
      0.91, Kruskal-Wallis test). The results suggest a learning curve lasting about 18
      24 months or 15 to 25 procedures before a plateau is reached. Improved results
      were associated with changes in case selection and operative tactics but not with
      reduced extent of lymphadenectomy. D2 gastrectomy should be restricted to
      specialist centres where adequate training and supervision can be provided during
      the learning curve.

PMID- 9014685
TI  - Double Y-V plasty for postsurgical anal stricture.

PMID- 9014686
TI  - Prognostic significance of lymph node metastasis in advanced carcinoma of the
      stomach.
AB  - This study attempted to clarify the prognostic factors in advanced gastric
      cancer, with special reference to lymph node metastasis. It was a retrospective
      study of 401 patients with stage III and IV gastric cancer operated on during the
      5 years from 1988 to 1993. A significant relationship was found between the 5
      year survival rate and (1) the ratio of the number of metastatic lymph nodes to
      the total number of dissected lymph nodes (ratios of 1-15, 16-30 and 31 per cent
      or more were associated with a 5-year survival rate of 81, 23 and 17 per cent
      respectively), (2) stage N1 or N2 of the Union International Contra la Cancrum
      tumour node metastasis classification (58 and 27 per cent respectively) and (3)
      the number of metastatic lymph nodes (1-3, 4-7 and 8 or more were associated with
      a 5-year survival rate of 67, 49 and 32 per cent respectively). Multivariate
      survival analysis using Cox's proportional hazard model was applied to these
      three forms of lymph node status. Among these three variables, the ratio of the
      number of metastatic lymph nodes to the total number of dissected lymph nodes was
      the most meaningful prognostic factor.

PMID- 9014687
TI  - Prognostic significance of lymph node dissection in gastric cancer.
AB  - The results for 162 patients who underwent curative gastrectomy for gastric
      cancer from January 1988 to June 1994 were analysed statistically with special
      reference to the effect of lymph node dissection. Median survival was 69.3 months
      and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence
      interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth
      of tumour invasion, node involvement, number of metastatic lymph nodes and type
      of lymphadenectomy were found to be significant factors related to survival time.
      Multivariate analysis with the Cox model and stratified for tumour node
      metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and
      the extent of lymphadenectomy (P = 0.003) affected survival independently. With
      respect to D1 lymphadenectomy, the relative risk associated with D2 and D4
      lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95
      per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients
      who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for
      those who had D4. These results suggest that extended lymphadenectomy (D2) and
      especially superextended lymphadenectomy (D4) can improve survival in patients
      with gastric cancer.

PMID- 9014688
TI  - Decreased E-cadherin expression is associated with haematogenous recurrence and
      poor prognosis in patients with squamous cell carcinoma of the oesophagus.
AB  - Reduced expression of E-cadherin is associated with tumour invasiveness and
      metastasis. To elucidate whether E-cadherin expression correlates with clinical
      outcome in patients with oesophageal cancer, 62 patients were investigated
      immunohistochemically using an anti-E-cadherin monoclonal antibody (HECD-1).
      Eight patients had normal levels of expression in the tumour, 25 had tumours that
      expressed high levels (50 per cent or more tumour cells staining positive for E
      cadherin) and 29 had tumours expressing low levels (less than 50 per cent of
      cells expressing E-cadherin). Patients with normally expressing tumours had a
      better prognosis at 3 years than those with low-expressing tumours (P < 0.05).
      Postoperative death was correlated significantly with lymphatic invasion, lymph
      node metastasis, E-cadherin expression and depth of invasion (P < 0.05).
      Furthermore, haematogenous recurrence was correlated with E-cadherin expression
      (rs = 0.38, P < 0.01) and blood vessel invasion (rs = 0.28, P < 0.05). These
      results suggest that evaluation of E-cadherin immunoreactivity may predict
      haematogenous recurrence and poor prognosis in patients with oesophageal cancer.

PMID- 9014689
TI  - Gastric tonometry and drain amylase analysis in the detection of cervical
      oesophagogastric leakage.

PMID- 9014690
TI  - Experimental oesophagogastric anastomosis: preliminary report of a new
      compression device that also fragments.
AB  - Fifteen Beagle dogs underwent oesophagogastric anastomosis with a new device
      which enables a 'sutureless' compression anastomosis. The device fragmented and
      was passed in bits anally without causing obstruction. Immediate bursting
      pressure, tested in five dogs, was between 175 and 190 mmHg. The anastomoses of
      the remaining dogs were examined macroscopically and microscopically from day 6
      to day 30. Healing was excellent with good muscular apposition and minimal
      residual inflammation.

PMID- 9014691
TI  - Salvage treatment for inoperable neck nodes in head and neck cancer using
      combined iridium-192 brachytherapy and surgical reconstruction.
AB  - The results of debulking surgery and re-irradiation with radioactive implants
      (brachytherapy) are reported for 39 patients with inoperable metastatic neck
      nodes from primary head and neck cancers. For 13 patients conventional salvage by
      partial debulking surgery and brachytherapy proved effective, with 68 per cent
      control at 1 year, but six patients suffered severe radiation fibrosis, necrosis
      and contractures. Some 26 patients were treated by combined tumour debulking,
      skin resurfacing and brachytherapy implant. Initial tumour control and freedom
      from serious toxicity was achieved in 24 patients. Local control was achieved in
      63 per cent of patients at 1 year, with a serious morbidity rate of 12 per cent.

PMID- 9014692
TI  - Conservative management of fibroadenoma of the breast.

PMID- 9014693
TI  - An evaluation of the POSSUM surgical scoring system.

PMID- 9014694
TI  - Skin from the amputated limb should not be wasted.

PMID- 9014695
TI  - Morphological classification of abdominal aortic aneurysm in selection of
      patients for endovascular grafting.

PMID- 9014696
TI  - Use of glyceryl trinitrate ointment in the treatment of anal fissure.

PMID- 9014697
TI  - Severe complications of perianal sepsis in patients with human immunodeficiency
      virus.

PMID- 9014698
TI  - Aspiring surgeons and temporary lecturer posts in anatomy.

PMID- 9014700
TI  - Routine preoperative infusion cholangiography at elective cholecystectomy: a
      prospective study in 694 patients.

PMID- 9014699
TI  - Blood flow in the lower limb after balloon angioplasty of the superficial femoral
      artery.

PMID- 9014701
TI  - Interstitial cystitis--an update.
AB  - Interstitial cystitis is a rare chronic debilitating condition predominantly
      affecting middle-aged women. The diagnosis, made from the combination of
      symptoms, cystoscopic findings and bladder biopsies, is often delayed because GPs
      are often unaware of the condition. The precise aetiology remains obscure and it
      is clear that there is much research that needs to be undertaken to shed any
      light on the various current aetiological theories. There is a wide assortment of
      therapies already available and many more currently under trial. Until there is
      further progress in the pathogenesis of IC, it seems unlikely that non-operative
      treatment will consist of anything but palliation. The only potential cures
      currently available are cystectomy and urinary diversion or surgical replacement
      of the bladder by enterocystoplasty.

PMID- 9014702
TI  - Alterations in pulmonary function after retroperitoneoscopic surgery.
AB  - OBJECTIVE: To evaluate and compare changes in pulmonary function after
      retroperitoneoscopic and open surgery. PATIENTS AND METHODS: From June 1994 to
      October 1995. 11 patients (five men and six women, mean age 44.7 years, range 29
      69) underwent retroperitoneoscopic procedures (Group 1) and 11 patients (eight
      men and three women, mean age 57.5 years, range 22-73) underwent flank-incision
      procedures (Group 2). The surgery comprised eight adrenalectomies and one each of
      nephroureterectomy, nephrectomy and pyelolithotomy in Group 1, and five
      adrenalectomies, four nephroureterectomies, one ureterolithotomy and one excision
      of a retroperitoneal tumour in Group 2. Pulmonary function tests (PFTs) were
      performed before and 3 days after surgery; the forced vital capacity (FVC),
      forced expiratory volume in 1 s (FEV1), forced expiratory volume at 25% (FEV25%),
      FEV1/FVC, vital capacity (VC), total lung capacity (TLC), residual lung volume
      (RV) and functional residual capacity (FRC) were compared between the groups. The
      post-operative changes in the PFTs were assessed using a paired t-test and the
      degree of change in both groups compared using the Mann-Whitney U-test. Other
      factors possibly influencing PFT were analysed using multiple regression.
      RESULTS: Pulmonary function was impaired in both groups on the third day after
      surgery. In Group 2, the FVC, FEV1, FEV25%, VC and TLC had declined significantly
      (all P < 0.05) from the pre-operative value. In Group 1, only the FVC and VC
      decreased significantly (P < 0.05). Post-operative pulmonary complications
      occurred in two patients in Group 2 but in none of those in Group 1, showing that
      pulmonary function was generally less affected in Group 1 than in Group 2.
      CONCLUSION: Although pulmonary function was impaired 3 days after surgery in both
      groups, retroperitoneoscopic surgery, by eliminating a large flank incision,
      caused less post-operative pulmonary dysfunction than open surgery.

PMID- 9014703
TI  - Micrometastatic adrenal invasion by renal carcinoma in patients undergoing
      nephrectomy.
AB  - OBJECTIVE: To examine adrenal invasion by renal cell carcinoma (RCC),
      particularly by adrenal micrometastasis, to determine whether adrenalectomy
      should be performed during radical nephrectomy. PATIENTS AND METHODS: From 1987
      to 1994, 129 patients with RCC (90 men and 39 women, mean age 61.4 years, range
      22-81) underwent radical nephrectomy with associated adrenalectomy because they
      had risk factors for adrenal invasion (tumour size > 5 cm. or tumour of the
      superior pole). Pathological examinations were carried out systematically and
      records of these examinations reviewed. The tumour size was recorded and the
      frequency of invasion calculated. RESULTS: There were 10 cases where the gland
      was invaded: one was a synchronous contralateral metastasis and nine (7%) were
      ipsilateral invasions of which two were tumours in the superior pole that invaded
      the gland by direct extension and the other seven invaded the gland by distant
      metastasis, six being micrometastatic (4.7%). A single micrometastasis was found
      in two cases (1.5%). There was no adrenal invasion by tumours of < 5 cm in
      diameter from the superior pole. When only tumours > 5 cm in diameter were
      considered, the ipsilateral invasion rate was 11% (9/80) and the micrometastatic
      rate was 7.5% (6/80). CONCLUSION: Adrenalectomy need not be performed routinely
      in small tumours which are detected early, but the possibility of adrenal
      micrometastasis from larger tumours (> 5 cm) should be considered.

PMID- 9014704
TI  - Partial ureteric obstruction: a study of Doppler ultrasonography and diuretic
      renography in different grades and durations of obstruction.
AB  - OBJECTIVES: To study the changes in renal resistive index (RI) and renal function
      with time during different grades of partial unilateral ureteric obstruction, and
      to determine the correlation between the ultrasonographic and renographic
      findings. MATERIALS AND METHODS: Ten dogs underwent right partial ureteric
      obstruction: grade 1 (mild) obstruction was applied in five dogs (group A) and
      grade 3 (moderate and severe) obstruction in the other five (group B). All dogs
      were assessed using excretory urography, diuretic renography with the calculation
      of half-time drainage (T 1/2) and bilateral renal Doppler ultrasonography before
      the experiment began, after one week of obstruction, and every 2 weeks during 8
      weeks of obstruction. RESULTS: In both groups, after the induction of right
      ureteric obstruction, there was a progressive decrease of effective renal plasma
      flow (ERPF) and a progressive increase of the RI of the right kidney at the end
      of the first and second weeks of obstruction, with an almost stable value
      thereafter. The decrease of ERPF and the increase of RI in the right kidney were
      correlated with the degree of obstruction. There was also a dramatic increase of
      T 1/2 of the right kidney that correlated with the degree of obstruction.
      Concomitantly, there was a significant compensatory increase of ERPF and a
      significant decrease of the RI of the left kidney in both groups. The
      compensatory increase in CRPF limited the loss in total ERPF in both groups. The
      contribution of obstructed kidney to the total ERPF was significantly reduced in
      both groups. At the end of the eighth week, taking all kidneys together, there
      was a statistically significant negative correlation between the ERPF and RI, and
      between ERPF and T 1/2 and a positive correlation between T 1/2 and RI.
      CONCLUSIONS: Unilateral partial ureteric obstruction increased the RI and T 1/2
      and decreased the ERPF of the corresponding kidney, together with a decrease of
      RI and an increase in ERPF of the contralateral kidney. The more severe the
      obstruction, the greater the increase in RI and T 1/2 and the decrease in ERPF.
      After the obstruction stabilized, RI and T 1/2 were positively correlated.

PMID- 9014705
TI  - The holmium: YAG laser for ureteric stones.
AB  - OBJECTIVE: To assess the efficacy of the pulsed holmium: YAG laser for the
      fragmentation of ureteric stones. PATIENTS AND METHODS: One hundred patients (72
      males and 28 females, age range 14 months-85 years) underwent 114 ureteroscopic
      procedures using either a 7.2 F semi-rigid or 9.5 F flexible ureteroscope. A
      holmium: YAG laser (Sunrise Technologies. Fremont, Ca, USA) was used for laser
      lithotripsy at a maximum energy of 1.0 J/pulse at 5 Hz. Most of the stones (46%)
      were located in the upper third of the ureter. The mean size of the stones was 9
      x 8 mm and the mean duration of the procedure was 73 min (including anaesthesia)
      with a mean hospital stay of 2.7 days. RESULTS: All the stones were accessed
      successfully using miniaturized endoscopes either retrogradely or antegradely.
      The holmium laser effectively fragmented all types of stones. Total clearance of
      all stones fragments was achieved in 87% of cases, with the best results obtained
      for stones in the lower third of the ureter (96%). The complications attributed
      directly to the laser included three strictures and three perforations of the
      ureteric wall. CONCLUSION: The holmium: YAG laser was effective in fragmenting
      ureteric stones irrespective of their hardness. However, it has the potential to
      damage the ureteric wall and must be used with caution.

PMID- 9014706
TI  - Long-term renal morphology and function following enterocystoplasty (refluxing or
      anti-reflux anastomosis): an experimental study.
AB  - OBJECTIVE: To study the morphology and function of the upper urinary tract over
      the long-term in dogs with an enterocystoplasty and a refluxing or anti-refluxing
      uretero-intestinal anastomosis. MATERIALS AND METHODS: Subtotal cystectomy and
      "cup" ileocystoplasty were performed in 13 dogs. The right ureter was implanted
      into the cystoplasty with a refluxing technique in seven and with an anti-reflux
      procedure in six dogs. The left renal unit acted as an intact control in 11 dogs,
      while in two the intramural part of the left ureter was incised to produce
      reflux. Thus, of the 26 renal units, nine had a refluxing junction (anastomosis),
      six were anti-refluxing and 11 served as intact controls. Total and separate
      glomerular filtration rates (GFRs) were measured preoperatively and regularly
      thereafter, and cystometry, urography and ascending enterocystography were
      performed. At necropsy, urine was obtained for culture from the cystoplasty and
      renal pelves, and both kidneys were examined histologically. RESULTS: The
      cystometric pressure was low in 12 of the 13 dogs: urography showed no
      obstruction. The fall in separate GFR did not differ significantly among the
      groups (with and without reflux protection, and control units). Reflux was
      detected in three of nine renal units with refluxing anastomosis and in three of
      11 control units. Bacteriuria was found in the cystoplasty in all dogs; the
      incidence in the upper urinary tract was seven of eight renal units with a
      refluxing anastomosis, one in five of those with an anti-refluxing anastomosis
      and three of nine control units. Pyelonephritis was found in none of the control
      kidneys, in six of nine kidneys with a refluxing and in two of six with an anti
      refluxing anastomosis: it was less severe in the latter. CONCLUSION: Refluxing
      ureteric implantation in a low-pressure enterocystoplasty was commonly associated
      with bacteriuria in the upper urinary tract and with pyelonephritis. Thus, anti
      reflux implantation was beneficial for renal preservation in this setting.

PMID- 9014707
TI  - Sociodemographic and symptomatic characteristics of women undergoing stress
      incontinence surgery in the UK.
AB  - OBJECTIVES: To: (i) describe the sociodemographic characteristics of women
      undergoing surgery for stress incontinence in the UK and the ways in which they
      differ from women of a similar age in the general population: (ii) the severity
      and impact of their symptoms and their expectations of surgery and: (iii) their
      general state of health. PATIENTS AND METHODS: A prospective cohort study was
      carried out on 442 women undergoing surgery for stress incontinence in 18
      hospitals in the North Thames region between January 1993 and June 1994.
      Sociodemographic factors, stress incontinence severity, symptom impact scores,
      and general health status were measured. RESULTS: Women undergoing surgery for
      stress incontinence were similar to their peers in the general population apart
      from being more likely to have smoked (61.4 against 51.1%), to have subsequently
      given up (39.5 and 25.3%) and to be of higher parity (> or = 4; 19.7 and 12.0%).
      Most women (81.6%) reported moderate to very severe stress incontinence. The
      impact of symptoms was correlated positively with severity (P < 0.001) after
      accounting for its positive correlation with mental health status (P < 0.005),
      socioeconomic status (P < 0.05) and its negative correlation with age (P < 0.02).
      Many women also suffered from other urinary symptoms including urgency (76%) and
      frequency (42.3%). Apart from their urinary problems, women were in good health
      (77% reported no or only mild coexistent conditions). However, a very high
      proportion (34.2%) had previously undergone a hysterectomy. CONCLUSIONS: These
      results suggest that women undergoing stress incontinence surgery are remarkably
      similar to their peers, apart from their primary condition. The effect that
      stress incontinence has on women's lives depends not only on the severity of the
      problem but also on other factors. The high rate of previous hysterectomy
      warrants further study.

PMID- 9014708
TI  - Comparison of real-time ultrasonography and magnetic resonance imaging in the
      assessment of urinary bladder volume.
AB  - OBJECTIVE: To compare estimates of bladder volume obtained by conventional real
      time ultrasonography with those obtained from magnetic resonance imaging (MRI) by
      the Cavalieri method of unbiased stereology. SUBJECTS AND METHODS: The study
      comprised nine subjects (four men and five women, mean age 23 years, range 18-34)
      with no history of bladder disease. Before micturition, each volunteer underwent
      ultrasonography, immediately followed by MRI. The volunteers then voided the true
      voided volume of urine was measured and the imaging protocols were repeated in
      the same order after micturition. The bladder volume was estimated from
      ultrasonography using the formula: volume = 0.7 (L x TS x AP), (where L is the
      maximum supero-inferior diameter. AP the maximum anteroposterior diameter and TS
      the maximum transverse diameter) and from MRI using the Cavalieri method. For
      each imaging modality, the volume of urine voided was estimated as the difference
      in the volume estimate before and after micturition. RESULTS: The mean percentage
      coefficient of variation for the estimates of bladder volume by ultrasonography
      was 2.17 before and 4.43 after micturition. There was no significant difference
      in the replicate estimates of each bladder diameter by ultrasonography before and
      after micturition (P = 0.98). The MRI method consistently underestimated the
      voided volume: the mean discrepancy between the estimated voided volume and the
      true voided volume was 7.7 ml, and -67.7 ml for the ultrasonographic and MRI
      estimates, respectively, which are significantly different (P = 0.02) when
      assessed using a multifactor ANOVA. Further analysis using multiple-range tests
      showed a significant difference between the voided volume estimated by MRI and
      the corresponding true voided volume. There was no difference between the voided
      volume estimated by ultrasonography and the corresponding true volume.
      CONCLUSION: Ultrasonographic estimates of voided volume were more reliable than
      the those obtained using the MRI method. This is possibly due to a delay between
      micturition and the acquisition of MR images after micturition, which allowed the
      bladder to partly refill with urine. The empirical approach using measurements
      from ultrasonograms provides a fast and reliable technique: ultrasonography
      remains the recommended imaging modality for estimating bladder volume.

PMID- 9014709
TI  - Detrusor myopathy: an accurate predictor of bladder hypocompliance and
      contracture in interstitial cystitis.
AB  - OBJECTIVE: To determine whether any histological characteristics within the
      detrusor in cases of early interstitial cystitis (IC) predict the subsequent
      development of severe symptoms due to bladder contracture. PATIENTS AND METHODS:
      The detrusor muscle component of bladder biopsies from 21 patients with IC was
      examined in sections stained with haematoxylin and eosin. Videocystometrography
      was performed at least 2 months after the biopsy and the patients were then
      followed up clinically for at least 3 years. RESULTS: The detrusor appeared
      normal in 13 patients; in eight there was evidence of detrusor myopathy. Patients
      with biopsies confirming detrusor myopathy were significantly more likely to have
      hypocompliant bladders than those with normal detrusor muscle histology (P <
      0.02). Over the following 3 years, six of the eight patients with detrusor
      myopathy developed progressively severe symptoms and required subtotal cystectomy
      and enterocystoplasty. None of the 13 patients without detrusor myopathy required
      bladder substitution. CONCLUSION: In IC, detrusor myopathy is associated with
      bladder hypocompliance. Patients with detrusor myopathy appear to have more
      severe disease and are more likely to progress to bladder contracture requiring
      substitution enterocystoplasty.

PMID- 9014710
TI  - The aetiological significance of human papillomavirus in bladder cancer.
AB  - OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA types 6,
      11 and 16 in histological sections of human bladder cancer. MATERIALS AND
      METHODS: Fifty-five formalin-fixed, paraffin-embedded bladder tumour specimens
      were analysed for the presence of HPV infection using Southern blotting DNA
      hybridization and radiolabelled probes for HPV DNA types 6/11 and 16. RESULTS:
      Despite the detection of HPV DNA type 6, 11 and 16 in positive control samples
      and the successful detection of HPV DNA in anogenital cancer using the same
      technique, no HPV DNA was found in any of the bladder tumour specimens examined.
      CONCLUSIONS: Using a technique with proven efficacy in the detection of HPV DNA
      from histological specimens, no HPV DNA was present in any of the bladder tumours
      examined. This finding is in agreement with most recently published studies
      suggesting that HPV has no significant role in the development of human bladder
      cancer.

PMID- 9014711
TI  - Cytokeratin 20 as an objective marker of urothelial dysplasia.
AB  - OBJECTIVE: To investigate the dysregulation of cytokeratin 20 (CK20) expression
      in urothelial dysplasia and its potential as a diagnostic aid. PATIENTS AND
      METHODS: Twenty-two patients were selected on the basis that they had undergone
      one or more biopsies showing dysplasia before the development of a transitional
      cell carcinoma (TCC): 15 of these patients also had a prior history of TCC. The
      dysplasia was classified as mild in 12, moderate in 14 or severe
      dysplasia/carcinoma in situ in 10 patients, ensuring that a spectrum of
      morphological appearances was represented. Control biopsies were obtained from
      seven children undergoing bladder reconstructions and 23 patients with recurrent
      urinary tract infections, haematuria or functional bladder symptoms, but no
      history of TCC. RESULTS: The expression of CK20 was restricted to superficial
      'umbrella' cells and occasional intermediate cells in the control biopsies, even
      in the presence of severe inflammation. In 31 of the 36 cases of dysplasia
      complete loss of restriction was seen at least focally with positive expression
      in all layers of the urothelium. CONCLUSION: The abnormal expression of CK20 is a
      reliable, positive marker of urothelial dysplasia in the urinary bladder.
      Immunostaining for CK20 is therefore a useful adjunct to morphology in the
      diagnosis of dysplasia, of particular value in the distinction from reactive
      states where diagnostic difficulties are greatest.

PMID- 9014712
TI  - A standard protocol for the evaluation of laser treatment of the prostate. The
      British Laser Urological Evaluation Society (BLUES)
AB  - OBJECTIVES: To present a standardized protocol, suitable for general use, for the
      evaluation of laser treatment of the prostate. METHODS: Many new operative
      treatments which are available to treat symptomatic prostatic enlargement are
      being accepted and offered to patients after scanty clinical evaluation, e.g.
      interventions using lasers. A consistent and standard protocol was developed,
      comprising data-recording sheets for patients' admission details, pre-operative
      assessments, operative details of laser ablation, post-operative in-patient
      progress and re-attendance, and subsequent out-patient follow-up. RESULTS: The
      protocol was tested by the members of BLUES and fulfilled their requirement for
      easy use in any department of Urology. It provides a simple way of accurately
      recording relevant data within a structured format with the additional advantage
      of permitting results to be expressed uniformly. CONCLUSION: The adoption of this
      protocol will allow valid comparisons of core data between studies assessing
      different procedures. The flexibility of the protocol enables it to be used, with
      minor modification, for the evaluation of any operative intervention aimed at
      relieving prostatic symptoms.

PMID- 9014713
TI  - Radioligand-binding analysis of human prostatic alpha-1 adrenoreceptor density
      following transurethral microwave therapy.
AB  - OBJECTIVE: To determine the effects of single-session transurethral microwave
      treatment (TUMT) on human prostatic alpha-1 adrenoreceptor density in patients
      with symptomatic bladder outlet obstruction caused by benign prostatic
      hyperplasia. PATIENTS AND METHODS: Radioligand-binding assays using 3H-prazosin
      were performed on prostatic tissue obtained from 25 patients, 10 of whom had
      received a single TUMT whilst the remaining 15 patients had not, and acted as
      controls. Prostatic tissue was obtained by cold-punch biopsy immediately before
      transurethral resection of the prostate from 20 patients (10 following microwave
      treatment and 10 controls) and from a further five patients at the time of
      retropubic prostatectomy; these five patients again had undergone TUMT. There
      were no statistically significant differences in several variables between the
      groups except for the weight of resected tissue, which was greater for the
      patients undergoing retropubic prostatectomy. Differences in the maximum receptor
      density (Bmax) and dissociation constant (Kd) were analysed statistically using
      the Mann-Whitney U-test because the data were non-parametric. RESULTS: Binding
      was saturable and a single class of high-affinity binding sites was identified in
      all cases. In the control group, the mean and 95% confidence interval (CI) alpha
      1 adrenoreceptor density (Bmax) was 96.4 (82.7-110.1) fmol/mg and the mean (95%
      CI) dissociation constant (Kd) was 0.56 (0.37-0.74) nmol/l. In those patients who
      had undergone TUMT, the mean Bmax was significantly lower at 71.3 (58.6-84.7)
      fmol/mg (P < 0.02) but the Kd of 0.56 (0.20-1.14) mmol/L was identical to that in
      the control group. CONCLUSIONS: Single-session TUMT, using a non-irrigated
      catheter, causes a significant reduction in prostatic alpha-1 adrenoreceptor
      density in the region of the prostate subjected to maximum beating. This may
      represent one possible mechanism of action by which microwave treatment exerts
      its beneficial effects.

PMID- 9014714
TI  - Reduction of length of stay and cost of transurethral resection of the prostate
      by early catheter removal.
AB  - OBJECTIVE: To determine whether early removal of the indwelling Foley catheter
      after transurethral resection of the prostate (TURP) significantly shortens the
      hospital stay without causing additional morbidity and thus saves costs. PATIENTS
      AND METHODS: For the year commencing 1 July 1991, 119 patients who had undergone
      TURP had their indwelling catheter removed on the first day after surgery. The
      results and morbidity of this group of patients were compared with those in 152
      patients undergoing TURP during the previous year. The economic consequences of
      this protocol were calculated using both Medicare and CHAMPUS data. RESULTS: The
      demographics of the patients in both groups were similar. Post-operative
      complications occurred in 5% of the study patients and in 6.6% of controls; a
      transfusion was required in 2.5% and 1.3%, clot retention developed in 1.7% and
      3.3% and the hospital stay was reduced from 3.1 to 1.28 days in the study and
      control patients, respectively. Using Medicare data, the mean cost saving of
      early catheter removal would be $829 and $1406 for patients aged < 70 and > 70
      years, respectively. For CHAMPUS patients, the cost saving would be $1983.
      CONCLUSION: Early removal of the catheter after TURP did not increase morbidity
      and maintained the efficacy of the procedure. If this practice was adopted
      nationally, the savings resulting from the reduction in hospital stay would be
      considerable.

PMID- 9014715
TI  - Do low molecular weight heparin and dextran increase the blood loss in
      transurethral resection of the prostate?
AB  - OBJECTIVE: To evaluate whether the use of dextran or the combination of low
      molecular weight heparin and dextran increases the blood loss in elective
      transurethral resection for benign prostatic hyperplasia. PATIENTS AND METHODS:
      This open randomized controlled study included 198 patients operated under spinal
      anaesthesia who were allocated to four groups differing in the combination of
      prophylactic treatment used for thrombosis and for the substitution of blood
      loss. The prophylactic treatment was either dalteparin sodium, continued each day
      until mobilization, or 3% Ringer dextran-60 just before operation and continued
      with 6% dextran-70 for 2 days post-operatively, and the volume substitute was
      Ringer dextran or Ringer's acetate. Thus, the four treatments (by prophylaxis and
      volume substitute, respectively) were dalteparin and Ringer's acetate, dalteparin
      and dextran, dextran and Ringer's acetate, and dextran and dextran. The
      haemoglobin lost to the irrigation fluid was measured and used to calculate blood
      loss. RESULTS: Patients receiving dextran had a larger post-operative and total
      blood loss than those who did not. The need for transfusion did not differ
      between the treatment groups. CONCLUSION: The combination of dalteparin and
      dextran was not associated with an increased blood loss above that with dextran
      alone.

PMID- 9014716
TI  - Comparative early results of transurethral electroresection and transurethral
      electrovaporization in benign prostatic hyperplasia.
AB  - OBJECTIVE: To compare the results of conventional transurethral electroresection
      of the prostate (TURP) and transurethral electrovaporization (TUEP) in patients
      with symptomatic benign prostatic hyperplasia. PATIENTS AND METHODS: The study
      comprised 46 patients with moderate or severe symptoms of prostatism and a
      maximal flow rate of < 15 mL/s. Pre-operatively, all patients underwent a digital
      rectal examination and the determination of prostatic volume by ultrasonography,
      and a symptom score, the maximal flow rate, post-void residual urine, routine
      biochemical variables and serum prostate specific antigen were measured. The
      haematocrit and blood Na+ levels were also determined pre-operatively and again
      24 h after the operation. Patients were divided randomly into two groups: the
      first underwent a conventional TURP and the second TUEP using 240-300 W of
      cutting current. Three months after operation, all the variables were remeasured
      and the values compared with those before treatment and between the groups.
      RESULTS: The improvements in symptom score, maximum flow rate and residual urine
      were slightly better after TURP than after TUEP but the differences between
      treatments were not statistically significantly different. However, TUEP used
      slightly less irrigant solution, allowed earlier removal of the urethral
      catheter, required no blood transfusions and was easier to perform. CONCLUSION:
      Although the improvements in the objective variables 3 months after TUEP were
      almost the same as after TURP, there were advantages in using less resources:
      further studies with more patients and a longer follow-up are required to
      determine the efficacy and safety of this procedure.

PMID- 9014717
TI  - Patient acceptability of transurethral incision of the prostate under local
      anaesthesia.
AB  - OBJECTIVE: To determine the acceptance by patients of transurethral incision of
      the prostate (TUIP) under local anaesthesia. PATIENTS AND METHODS: The study
      comprised 30 consecutive patients who elected to undergo local anaesthesia for
      TUIP and were treated between December 1994 and September 1995. Twenty-two were
      considered a high risk for general anaesthesia and eight patients chose local
      anaesthesia for personal reasons. Patients were premedicated (opioid and
      benzodiazepine) and 1% lidocaine was infiltrated transurethrally using an
      endoscopic needle. The level of acceptance was determined using an immediate post
      operative questionnaire which included a linear visual analogue scale (VAS) to
      rate pain. RESULTS: No patient required conversion to another type of anaesthesia
      and there were no complications related to the local anaesthesia. The mean (SE)
      VAS score was 3.2 (1.7) and the questionnaire results showed that 83% of the
      patients did not consider that general anaesthesia was necessary for the
      operation and that 90% would agree to undergo the procedure again under local
      anaesthesia. CONCLUSION: TUIP under local anaesthesia was well tolerated in
      motivated patients. We recommend it as the operation of choice for the relief of
      obstruction in high-risk patients with a small benign prostatic hyperplasia.

PMID- 9014718
TI  - Anti-androgenic effects of combination finasteride plus flutamide in patients
      with prostatic carcinoma.
AB  - OBJECTIVES: To determine the anti-androgenic effects and safety of the
      combination of finasteride and flutamide in men with prostate cancer. PATIENTS
      AND METHODS: Seventeen men with various stages of prostate cancer, all of whom
      were candidates for androgen deprivation therapy, were treated with finasteride
      plus flutamide and were followed for a mean of 13.6 months using measurements of
      serum prostate specific antigen (PSA), and an assessment of regression and side
      effects. RESULTS: The initial median PSA level was 19.8 ng/mL: at 3, 6 and 12
      months the median PSA had fallen to 1.2, 0.85 and 0.8 ng/mL, respectively. In
      four patients followed for 2 years, the anti-neoplastic effects were sustained.
      Patients with initially palpable disease had regression, as assessed by a digital
      rectal examination. Side-effects included gynaecomastia (five patients), mildly
      elevated hepatic transaminases (two) and diarrhoea (one). Most men maintained
      their previous sexual function. CONCLUSIONS: Early results suggest that the
      combination of finasteride and flutamide provides significant anti-androgenic
      therapy and maintains sexual function in most men. A further investigation with
      more patients and a longer follow-up is warranted.

PMID- 9014719
TI  - A review of radical prostatectomy from three centres in the UK: clinical
      presentation and outcome.
AB  - OBJECTIVE: To examine critically the clinical presentation, pathological stage
      and outcome in patients selected for radical prostatectomy combining data from
      three centres where the operation has been carried out routinely for more than 5
      years. Comparisons were made between impalpable tumours presenting at
      transurethral resection of the prostate (TURP) for clinically benign disease,
      tumours diagnosed at needle biopsy performed because the serum prostate-specific
      antigen (PSA) was elevated, and palpable, clinically localized cancer detected by
      digital rectal examination (DRE). PATIENTS AND METHODS: Clinical and pathological
      findings recorded in the hospital notes of 183 patients who had undergone
      exploration for radical prostatectomy at St Bartholomew's Hospital, London,
      Southmead Hospital, Bristol, and the Royal Infirmary, Stirling, between 1987 and
      1994 were transcribed onto a proforma and analysed. Patients were categorized by
      clinical stage and the relationships between clinical presentation, serum PSA
      level, pathological stage, tumour grade and outcome were examined. RESULTS: The
      pathological extent of clinically unsuspected cancer identified at TURP was
      highly variable. Well-differentiated tumours occupying < 5% of the TURP specimen
      were generally found to be less extensive at subsequent radical prostatectomy
      than either impalpable malignancy diagnosed by needle biopsy performed because
      PSA levels were raised or palpable tumours associated with a unilateral
      abnormality on DRE. Unsuspected tumours diagnosed at TURP that were less than
      well differentiated or occupied > 5% of the surgical specimen were more commonly
      associated with extra-prostatic invasion or metastatic disease than were tumours
      detected by raised PSA levels or an abnormal DRE. Serum PSA did not reliably
      predict either clinical stage or pathological extent, but no patient with nodal
      metastases had a PSA level of < 12 ng/mL. Similarly, pathological stage could not
      be predicted confidently from the whole-tumour grade ascertained after surgery.
      The extent of malignancy in patients referred because of lower urinary tract
      symptoms was not significantly different from that among patients referred
      specifically because the PSA level was raised or the DRE was abnormal. However,
      there was a trend for patients found to have cancer in specific screening
      programmes to have a malignancy that was less extensive and therefore more
      frequently confined to the gland than in those not identified by screening.
      CONCLUSION: Among patients with unsuspected malignancy diagnosed at TURP, those
      with well differentiated tumours in < 5% of the specimen had significantly less
      advanced disease than men found to have less differentiated or more extensive
      malignancy in the resected specimen. Impalpable cancer associated with a raised
      PSA level diagnosed by needle biopsy represented an intermediate group comparable
      to those with unilateral palpable malignancy. This suggests that needle biopsies
      may be worthwhile in some patients with an apparently benign prostate and raised
      PSA level with a view to identifying clinically significant but potentially
      curable cancer. Screening may detect less extensive tumours, but the natural
      history of these cancers is unknown and observed survival will be subject to lead
      time and length bias when compared to symptomatic disease. Prospective randomized
      studies of both screening and treatment modalities, including surgery and
      radiotherapy, are required to define the impact of radical prostatectomy on
      disease-specific survival in men with early stage prostate cancer.

PMID- 9014720
TI  - Experience with low-dose oestrogen in the treatment of advanced prostate cancer:
      a personal view.
AB  - OBJECTIVE: To re-evaluate the treatment of advanced prostatic carcinoma with
      diethylstilboestrol (DES) in low dosage in relation to the degree of suppression
      of plasma testosterone. PATIENTS AND METHODS: The study comprised 106 patients
      with advanced carcinoma of the prostate (89 with T3/4 M1 and 17 with T3/4 N0/1
      M0) who were treated with 1 mg/day of DES. The response was assessed clinically
      and by the change in plasma prostate specific antigen, prostatic and phosphatase
      and alkaline phosphatase, and plasma testosterone was monitored regularly. In a
      few patients it was possible to reduce the dose to 0.5 mg/day DES; in others, the
      initial response was not sustained and they were treated with an increased dose
      of DES or bilateral orchidectomy. RESULTS: Seventy patients (Group 1) showed a
      sustained response to 1 mg/day of DES (0.5 mg/day in three) and 50 remained in
      remission at a mean of 21 months of treatment. Of the 36 patients offered
      secondary treatment, 12 (Group 2) responded with a second remission. Only 27% of
      patients had mean testosterone levels in the castrate range (0-2 nmol/L) but most
      in Group 1 had mean levels of < 10 nmol/L, whilst in 10 of the 12 patients in
      Group 2, the level was > 10 nmol/L. Overall times to progression and death were
      comparable with the results of conventional monotherapy or combination treatment
      and complication rates were acceptable. CONCLUSION: Low-dose oestrogen therapy (1
      mg/day of DES) is cheap, effective and caused few side-effects, none of which was
      life-threatening. In many patients, only minimal suppression of the plasma
      testosterone was required and the response appeared to be qualitative, although
      there was considerable variation in the threshold of response. A randomized trial
      of oestrogen, in a minimal dose adjusted to the requirements of the individual
      patient, against conventional hormone treatment now seems justified.

PMID- 9014721
TI  - A one-stage dorsal free-graft urethroplasty for bulbar urethral strictures.
AB  - OBJECTIVE: To report the use of one-stage dorsal free-graft urethroplasty to
      reduce the incidence of urethrocele. PATIENTS AND METHODS: From 1990 to 1994, 20
      men (age range 21-86 years) underwent a one-stage dorsal free-graft urethroplasty
      of bulbar urethral strictures (iatrogenic in 12, traumatic in three, inflammatory
      in three and unknown in two). All patients except one had been treated previously
      by optical urethrotomy from one to 14 times. RESULTS: Temporary fistulae were
      detected on post-operative urethrography in three patients with particularly long
      grafts, but they all resolved spontaneously. Within a mean follow-up of 46
      months, only one patient had a short recurrent stricture, which was treated
      successfully by optical urethrotomy. Two patients complained of post-voiding
      dribbling, but radiographic studies never showed graft weakening and the urinary
      flow rate was always > 14 mL/s. CONCLUSION: Free skin grafts can be applied
      successfully to the dorsal aspect and by doing so the complications of urethral
      reconstruction can be reduced.

PMID- 9014722
TI  - Inflatable penile prosthesis: results of 150 cases.
AB  - OBJECTIVES: To evaluate the reliability of the prosthesis and the rate of
      complications in organically impotent men who were implanted with an inflatable
      penile prosthesis. PATIENTS AND METHODS: A consecutive series of 150 men (mean
      age 60 years, range 25-90) were followed for a mean of 19 months (range 0-65)
      after implantation of the Mentor Alpha 1 penile prosthesis. Information was
      obtained from their medical records and by telephone interview, but the
      satisfaction of the patients was not assessed quantitatively. RESULTS: There were
      no complications in 145 of the patients and they currently have functioning
      prostheses. Complications occurred in five patients (3%), including two peri
      prosthetic infections (1%) and two intra-operative and one post-operative
      cylinder aneurysm. Complications requiring re-operation occurred in three (2%) of
      patients; none of the implants leaked. CONCLUSIONS: These results suggest that
      for men with organic impotence, a Mentor Alpha 1 implant is an effective
      treatment option with acceptable morbidity and good mechanical reliability.

PMID- 9014723
TI  - A follow-up study of pre-natally detected primary vesico-ureteric reflux: a
      review of 61 patients.
AB  - OBJECTIVE: To describe the pre- and post-natal characteristics of primary vesico
      ureteric reflux (VUR) in a retrospective study of babies presenting with VUR
      suspected from pre-natal ultrasonography. PATIENTS AND METHODS: Between 1984 and
      1994. 61 children (41 boys and 20 girls) with primary VUR were followed for 2
      years after the pre-natal detection of urinary tract anomalies. Patients with VUR
      secondary to infravesical obstruction and duplex systems were excluded. The mean
      age at ante-natal diagnosis was 28.4 weeks of gestation; in 37 the reflux was
      bilateral and 98 refluxing units were reviewed. RESULTS: According to the
      international classification of VUR, 8% were grade 1, 32% grade 2, 38% grade 3,
      16% grade 4 and 6% grade 5. Twelve patients (22 refluxing units) underwent
      ureteric re-implantation. Six kidneys showed renal scars on isotope renography
      and two nephrectomies were carried out in patients < 2 years old: in 40 patients
      (64 renal units) the VUR resolved spontaneously. Of the latter, eight were grade
      1, 20 grade 2, 27 grade 3 and nine grade 4: seven patients (10 refluxing units)
      are still being followed and awaiting a decision on treatment. CONCLUSION: This
      study confirms the predominance of boys in those with ante-natally suspected VUR.
      The spontaneous resolution during the first 2 years of life was apparent in most
      cases, even in those with severe reflux (grade 3-5).

PMID- 9014724
TI  - Burns to the genitals and the perineum in children.
AB  - OBJECTIVE: To determine the management of perineal and genital burns in children.
      PATIENTS AND METHODS: Twenty-seven children (aged 6 months to 12 years) suffering
      from genital or perineal burns between 1981 and 1995 were reviewed. Most burns
      occurred in boys (70%), were due to scalds (85%) and caused superficial second
      degree lesions (63%). The initial treatment consisted of topical antimicrobials
      or grafting with allografts. RESULTS: Spontaneous healing by conservative
      therapy, not early excision therapy, occurred in 96% of the patients.
      Contractures occurred in two patients and were treated with multiple Z-plasties
      and circumcision. CONCLUSION: The management of perineal and genital burns in
      children should be conservative.

PMID- 9014725
TI  - Intravesical uretero-ureterostomy for vesico-ureteric reflux (VUR) in duplex
      ureters: a method for the correction of VUR.

PMID- 9014726
TI  - Retroperitoneoscopic stenting of the ureter.

PMID- 9014727
TI  - Ring the fire brigade.

PMID- 9014728
TI  - Genital self-mutilation: sub-preputial space--the final frontier?

PMID- 9014729
TI  - Bilateral xanthogranulomatous pyelonephritis in a child.

PMID- 9014730
TI  - Acute retention of urine due to a loose peritoneal body.

PMID- 9014731
TI  - Ureteroperitoneal fistula secondary to tubal sterilization by laparoscopy.

PMID- 9014732
TI  - Unusual presentations of pericolic abscess following nephrectomy.

PMID- 9014733
TI  - Altered seminal ejaculate consistency due to schistosomiasis.

PMID- 9014734
TI  - Paravesical mass following inguinal herniorraphy.

PMID- 9014735
TI  - Somatostatinoma in a horseshoe kidney.

PMID- 9014736
TI  - Secondary megaprepuce.

PMID- 9014737
TI  - SI units in urology: behind the times--or convenient tradition?

PMID- 9014738
TI  - The ICS-BPH study.

PMID- 9014739
TI  - Compartment syndrome.

PMID- 9014740
TI  - Ambulatory urodynamic monitoring.

PMID- 9014741
TI  - Cancer and the mind--do we still believe Galen?

PMID- 9014742
TI  - The diagnostic information of tests for the detection of cancer: the usefulness
      of the likelihood ratio concept.
AB  - No single test is perfect and without false-negative and/or false-positive
      results. Consequently, the clinician is perpetually confronted with incertitude
      about the true disease state of the patient. In oncology, these diagnostic errors
      may have harmful consequences for the patient. It is, therefore, imperative that
      the clinician knows how often these errors occur, which implies a quantitative
      evaluation of a test. With this knowledge, the test result must subsequently be
      interpretated within the clinical framework. Bayes' theorem provides a simple and
      useful mathematical model for the integration of measures of test performance and
      clinical data. Traditionally, sensitivity and specificity are used to describe
      test performance. However, this approach requires that the conclusion of the test
      is dichotomised into 'normal' and 'abnormal'. Few tests have a natural binary
      outcome. A test parameter that is applicable to all types of test outcome scales
      and, at the same time, provides the opportunity to determine the gain in
      diagnostic information by applying Bayes' theorem, is therefore mandatory. The
      likelihood ratio meets these conditions. The application of this concept for both
      the evaluation and the interpretation of various types of tests used in cancer
      patients is demonstrated.

PMID- 9014743
TI  - Life events and the risk of breast cancer: a case-control study.
AB  - A case-control study was undertaken to investigate the possibility of an
      association between stressful life events and the development of breast cancer.
      Ninety-nine breast cancer cases, and 99 controls matched by age and area of
      residence, completed a life events inventory to measure life change and distress
      scores over a 2-year and a 10-year period. Study subjects were also interviewed
      to establish potential breast cancer risk factors; their height and weight were
      measured; they completed a food frequency questionnaire and provided a fasting
      blood sample for hormonal assay. After adjusting for potential confounders, women
      with a 10-year life change score greater than 210 (i.e. the highest quartile) had
      4.67 times the risk of developing breast cancer, compared with those in the
      lowest quartile (P < 0.05).

PMID- 9014744
TI  - Pyridinium cross-links in multiple myeloma: correlation with clinical parameters
      and use for monitoring of intravenous clodronate therapy--a pilot study of the
      German Myeloma Treatment Group (GMTG).
AB  - The relevance of quantitative determinations of urinary deoxypyridinolines (DPY)
      and pyridinolines (PY), and of serum type I collagen carboxyterminal cross-linked
      telopeptides (ICTP), has been evaluated for patient monitoring in multiple
      myeloma (MM). In 178 untreated MM patients, a clear correlation was found between
      ICTP concentrations, bone destructions and serum calcium levels. Furthermore,
      serum ICTP, urinary DPY and PY concentrations were estimated before and during
      treatment in a further 33 MM patients randomly allocated to four groups receiving
      intravenous melphalan/prednisone (MivP) chemotherapy alone, or MivP in
      combination with three different doses of i.v. clodronate. 1800 mg of i.v.
      clodronate combined monthly with MivP induced a rapid and sustained reduction in
      bone resorption parameters to the normal range, a result not obtained with either
      MivP alone, or with a lower clodronate dose. While confirming the relevance of
      determining pyridinium cross-links for estimating bone resorption in MM, our data
      indicate that measurements of these parameters could be useful for dose finding
      and monitoring of bisphosphonate therapy.

PMID- 9014745
TI  - High-dose melphalan with re-infusion of unprocessed, G-CSF-primed whole blood is
      effective and non-toxic therapy in multiple myeloma.
AB  - In order to shorten the pancytopenic period following high-dose melphalan 140
      mg/m2 (HDM) treatment of multiple myeloma patients, we studied the effects of re
      infusing granulocyte colony stimulating factor (G-CSF) [Filgrastim, Neupogen]
      primed unprocessed whole blood. 30 patients with multiple myeloma were treated
      with HDM. One litre of blood after 5 or 6 days stimulation with G-CSF (10
      micrograms/kg) was drawn, kept unprocessed for 1 day and re-infused 24 h after
      chemotherapy. Time to granulocyte recovery (> 0.5 x 10(9)/1) and platelet
      recovery (> 20 x 10(9)/1) were assessed as well as length of hospital stay,
      number of transfusions and antibiotic use. These 30 patients were compared with
      20 historical control patients who were similarly treated but without stem cell
      support. The response rate was 75% (21/28) including a complete remission (CR)
      rate of 29% (8/28). Two early deaths due to Aspergillus pneumonia were observed.
      The median overall survival after HDM has not been reached after a median follow
      up of 14 months. 10 patients showed progression at a median of 7 months.
      Currently, 23 patients are alive with a median follow-up time of 14 months.
      Haematological recovery was significantly faster in the study group as compared
      to the historical control group. The neutrophil count reached 0.5 x 10(9)/1 at a
      median of 14 days after infusion of 1 litre of unprocessed whole blood compared
      with 38 days in the historical control group. A platelet count of 20 x 10(9)/1
      was reached at a median of 26 days compared with 36 days in the historical
      control group. Length of hospital stay decreased from a median of 43 to 18.5
      days. The number of days with antibiotics was reduced from a median of 21 to 6
      days. HDM is effective therapy for multiple myeloma. Toxicity of the regimen is
      considerably reduced by the use of G-CSF-stimulated unprocessed whole blood, an
      easy to perform and cheap technique to mobilise and collect stem cells.

PMID- 9014746
TI  - Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients.
      Feasibility, toxicity and long-term results of a phase II study.
AB  - The aim of this study was to evaluate the feasibility, the response rate and the
      effect on survival of full dose polychemotherapy delivered concurrently with
      bifractionated radiotherapy at a radical dose, in a subset of patients with
      marginally resectable or unresectable stage IIIA-B non-small cell lung cancer
      (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m2 for 1 day plus
      etoposide 120 mg/m2 for 3 days delivered from day 1 to day 22, plus radiotherapy
      delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to
      33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal
      fractions. After surgery, three additional courses of cisplatin plus etoposide
      were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC
      (19 were judged as having marginally resectable, 20 as having unresectable
      disease) were entered into the study. Out of 39 patients (22 squamous cell
      carcinoma, 17 adeno/large cell carcinoma), 24 had stage IIIa (62%) and 15 stage
      IIIb (38%). Median PS was 80 (70-90). A total of 78 (74 evaluable) concurrent
      cycles of pre-operative chemoradiotherapy were delivered. The prominent side
      effect was leucopenia: leucopenia > or = grade 3 at nadir occurred in 20 cycles
      (27%), thrombocytopenia > or = grade 3 at nadir in seven cycles (9%), 19 patients
      (54%) had a treatment delay of 1 week between the two cycles. Other important
      toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients
      (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR
      (complete response), 16%; 19 PR (partial response), 51%). A resection was
      subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable
      (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had
      an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients
      (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%)
      macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5
      relapsed locally and 11 only distantly. At present, with a follow-up ranging from
      64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4
      (17%) are alive without evidence of disease. Median survival was 16 months, with
      18% 3-year survivors and 13% 5-year survivors. Resected patients had a median
      survival of 21 months, versus 10 months for unresected patients (P = 0.01). No
      significant difference was evident between stage IIIa and stage IIIb patients.

PMID- 9014748
TI  - No age limit for radical radiotherapy in head and neck tumours.
AB  - The elderly are often treated less aggressively in an attempt to preserve their
      quality of life with regards to toxicity. However, there are few data regarding
      the acute and late toxicity of radiotherapy (RT) in elderly patients. From
      February 1980 to March 1995, 1589 patients with head and neck cancers who
      enrolled in EORTC trials received RT and were available for analysis on RT
      toxicity. Patients over 65 years of age were in excess of 20%. Data regarding age
      and acute objective mucosal reactions were available for 1307 patients and 1288
      had toxicity > or = grade 1. Age and acute functional mucosal reactions were
      registered for 838 patients and 824 patients had toxicity > or = grade 1.
      Bodyweight alteration during treatment was available in 1252 patients; it
      increased in 153 patients and decreased in 1099 patients. Late toxicities were
      examined only if they occurred before an eventual tumour failure in order to
      avoid confusion between effects of first- and second-line treatments. 749
      patients were available for analysis of which 646 had late toxicity grade > or =
      1. Survival and toxicity were examined in different age ranges from 50 to 75
      years and over. There was no significant difference in survival between each age
      group. A trend test was performed to assess any correlation between age and the
      acute occurring toxicity. There was no significant difference in acute objective
      mucosal reactions (P = 0.1) and in weight loss > 10% (P = 0.441). In contrast,
      older patients had more severe (grade 3 and 4) functional acute toxicity (P <
      0.001) than younger patients. We evaluated the probability of late toxicity
      occurrence in relation to time with the Kaplan-Meier method and the logrank test
      in each age group. Eighteen per cent of patients were free of late effects at 5
      years, the logrank test showing no significant difference between ages (P =
      0.84). In conclusion, chronological age is irrelevant for therapeutic decisions.

PMID- 9014747
TI  - A comparison of epidermal growth factor receptor levels and other prognostic
      parameters in non-small cell lung cancer.
AB  - Epidermal growth factor receptor (EGFR) was measured using a competitive
      radioligand binding assay in membrane preparations from 74 primary human non
      small cell lung cancer (NSCLC) tissues and 20 pathologically normal peripheral
      lung tissues. The mean EGFR level in tumours was 30.38 fmol/mg (+/-41.95 S.D.) of
      membrane protein (mg.p), significantly higher (P = 0.00016) than in normal
      tissues (mean, 10.26 +/- 10.02 fmol/mg.p). The mean EGFR concentration was also
      significantly higher in pathological stage IV tissue than in stages I (P = 0.049)
      and II (P = 0.040), and the mean EGFR concentration was significantly higher in
      cases with mediastinal involvement than in cases without it (P = 0.029). The mean
      EGFR level was higher in DNA aneuploid and multiploid cases than in DNA diploid
      cases, but there was no significant difference. No significant relationships were
      found to exist between receptor concentrations and pathological tumour size or
      histological type, or patient gender or age. From the above findings, a possible
      prognostic role for EGFR in primary NSCLC should be investigated.

PMID- 9014749
TI  - A comparison of dosimetric methods in isolated limb perfusion with melphalan for
      malignant melanoma of the lower extremity.
AB  - The three dosimetric schedules currently used in isolated limb perfusion with
      melphalan for malignant melanoma of the lower limb were compared in a series of
      51 patients. The doses prescribed by each of the three methods (based on total
      body weight (TBW), limb tissue volume (LTV) and total blood volume in the
      perfusion circuit (TBV)) were calculated for all patients and were then compared
      using Wilcoxon's signed-rank test. This revealed that the method based on TBV
      consistently prescribed much lower doses of drug than either of the other two
      methods. Pharmacokinetic profiles of melphalan obtained by HPLC analysis of blood
      samples during the procedure also showed that the method did not reliably predict
      the concentration of melphalan achieved in the perfused limb. The dosimetric
      schedule based on LTV prescribed slightly higher doses than that based on TBW.
      However, the technique is more difficult to practise due to the problems of
      measuring the limb volume by immersion. We conclude that the dosimetric schedule
      based on TBW is the most appropriate by virtue of its simplicity, the high doses
      of melphalan which it prescribes, and the well-controlled toxicity which it
      produces.

PMID- 9014750
TI  - Percentage of free serum prostate-specific antigen: a new tool in the early
      diagnosis of prostatic cancer.
AB  - Prostate-specific antigen (PSA) is a protease able to bind to serum antiproteases
      as alpha 1 antichymotrypsin (ACT). Free PSA (FPSA) corresponds to the fraction of
      total PSA (TPSA) which is unbound to ACT. Specific detection of the FPSA seems to
      be a valuable tool in the distinction between prostatic cancer (PCa) and benign
      prostatic hyperplasia (BPH). Our aim was to evaluate retrospectively the
      FPSA/TPSA ratio in comparison to TPSA or FPSA determination, using two new
      immunoradiometric assays (PSA-RIACT and FPSA-RIACT, CIS bio international, Gif
      Sur Yvette, France) in the early diagnosis of PCa. 256 men, with TPSA levels
      between 0.7 and 44.7 ng/ml (median age = 69 years), including 164 sera obtained
      from patients with BPH and 92 sera from patients with untreated PCa were assayed.
      All diagnoses were histologically confirmed and patients tested before any
      adjuvant treatment. The evaluation of the median FPSA/TPSA ratio in the two
      groups showed significantly different values (BPH group: 24.2%, PCa group: 12.1%,
      P < 0.0001). By R.O.C. (Receiver-Operating-Characteristics) analysis, we show
      that the FPSA/TPSA ratio is the method of choice for discriminating BPH and PCa,
      since the area under curve is the greatest for the FPSA/TPSA ratio curve, as
      compared to the TPSA or FPSA curves (P < 0.0001). The best accuracy (number of
      true positive + true negative/total = 82.4%) was obtained with a FPSA/TPSA ratio
      < or = 15% with high odds ratio (20.5; confidence interval (CI): 11.2; 37.7). Of
      interest, similar results were also confirmed even in the subpopulation with
      serum TPSA levels between 2.5 and 10 ng/ml (161 patients including 99 BPH and 62
      PCa). We thus confirm that combined serum measurement of FPSA and TPSA is of
      particular interest in the early diagnosis of PCa for patients with non
      suspicious digital rectal examination and a TPSA value between 2.5 and 10 ng/ml.
      In those patients, biopsy should be reserved to the cases with FPSA/TPSA below
      15%, which allows significant odds ratio (12.8; CI: 5.2; 31.4). Otherwise, to
      avoid the risk of missing any PCa, usual follow-up with combined TPSA and FPSA
      determination would be required with the same criteria of biopsy (i.e. FPSA/TPSA
      ratio < or = 15% when TPSA value is between 2.5 and 10 ng/ml; or TPSA > 10
      ng/ml).

PMID- 9014751
TI  - Fibromatosis and fibrosarcoma in infancy and childhood.

PMID- 9014752
TI  - Time course of methotrexate polyglutamate formation and degradation in the pre-B
      leukaemia cell line Nalm6 and in lymphoblasts from children with leukaemia.
AB  - With the aim of investigation, the mechanisms of resistance to methotrexate (MTX)
      in children refractory to leukaemia-treatment, we established a method of
      analysing MTX metabolism in Nalm6 cells (human pre-B). The optimal extracellular
      concentration for MTX uptake and MTX polyglutamate (MTXPG2-6) formation at a
      density of 5 x 10(6) cells/ml was 1 microM 3H-MTX. After 15 h incubation at this
      concentration, a plateau of 5 pmol/10(6) cells of total MTX accumulated in the
      form of equal amounts of polyglutamates 3, 4 and 5 and low amounts of MTX and
      polyglutamates 2 and 6. MTX preloaded cells rapidly lost MTX and MTXPG2 in MTX
      free medium, while MTXPG5 was still formed and then degraded very slowly. After 8
      h in medium without MTX, 40% of total MTXPG was lost, after 24 h, 70%. The method
      is feasible for patient blasts. The number of blasts isolated from bone marrow
      after diagnosis is enough to perform small kinetic studies. The uptake of MTX
      into patient blasts is about 1/10 of that in Nalm6 cells.

PMID- 9014753
TI  - Alcohol and breast cancer in the Swiss Canton of Vaud.
AB  - The relationship between alcoholic beverage drinking and the risk of breast
      cancer was considered using data from a case-control study of breast cancer
      conducted between 1990 and 1995 in the Swiss Canton of Vaud on 230 incident cases
      of breast cancer below age 75 years, linked with the Vaud Cancer Registry, and
      507 controls admitted to the same network of hospitals for a wide spectrum of
      acute, non-neoplastic, non-hormone-related conditions. Overall, 70.4% of cases
      versus 57.4% of controls consumed alcohol, corresponding to a multivariate odds
      ratio (OR) of 1.5 (95% confidence interval (CI): 1.1-2.2). The ORs were 1.3 for <
      1 drink per day, 1.8 for 1 to 2, 1.5 for 2 to 4, and 2.7 for > 4 drinks per day,
      and the trend in risk with dose was significant. The association was consistent
      for wine (OR = 2.0), beer (OR = 2.6) and spirits (OR = 2.0) and was apparently
      stronger in premenopausal women, whereas no noticeable interaction was observed
      with any of the hormonal or reproductive risk factors for breast cancer. The
      alcohol-related risk was unrelated to duration; the OR was 1.8 for women who
      started drinking below the age of 30 years and 1.4 for those starting at the age
      of > or = 30 years. Thus, the present study confirms that alcohol is a correlate
      of breast cancer risk in this European population, where alcohol drinking among
      women is common and relatively high. Assuming that this association reflects
      causality, in terms of attributable risk, alcohol could explain 25% (8-42%) of
      breast cancer cases.

PMID- 9014754
TI  - Survival in small intestinal adenocarcinoma.
AB  - All cases of adenocarcinoma in the duodenum (n = 263) and jejunum/ileum (n =
      663), diagnosed between 1960 and 1988, were recruited from the Swedish Cancer
      Registry. Corrected and overall survival were investigated by sex, age and year
      of diagnosis with life-table and Cox proportional hazards analyses. The corrected
      5- and 10-year survival rates were 39% and 37% for duodenal tumours and 46% and
      41% for those in jejunum/ileum (P = 0.16 for difference between sites). The
      corrected 5- and 10-year survival rates were 52% and 48% for women and 40% and
      34% for men with tumours in jejunum/ileum (P = 0.0095 for difference by sex)
      while no such relation was found in duodenal tumours (P = 0.84). Survival
      correlated with age at diagnosis for duodenal tumours (P = 0.03377). A Cox
      proportional hazards analysis revealed a temporal trend with more favourable
      prognosis in recent years. This study confirms that prognosis of small bowel
      adenocarcinoma is serious, but gives a more optimistic outlook than many hitherto
      published series.

PMID- 9014755
TI  - Elevation of protein kinase A and protein kinase C activities in malignant as
      compared with normal human breast tissue.
AB  - Because of their central role in the transduction of extracellular signals,
      protein kinases A (PKA) and C (PKC) are critical enzymes in the control of
      cellular proliferation and differentiation. We have measured the catalytic
      activity of PKA and PKC, as well as the regulatory subunit expression for PKA, in
      paired samples of normal and malignant breast tissue from 13 patients with breast
      cancer. Paired non-parametric (Wilcoxon) analysis revealed significantly higher
      values for both basal (P = 0.0002) and total (P = 0.0002) PKA catalytic activity
      in malignant compared with normal breast in all 13 paired tissue samples.
      Expression of both R1- and RII-PKA regulatory subunits were also higher in
      malignant tissue from 12 (P = 0.0005) and 9 (P = 0.01) of the 13 pairs,
      respectively. However, the degree of RI-subunit overexpression in malignant
      tissue was greater than that of the RII-subunit, as demonstrated by an increase
      in the RI/RII subunit ratio in 10 of the 13 paired samples (P = 0.017). Total PKC
      catalytic activity was elevated in 11 of the 13 malignant tissue specimens when
      compared with corresponding normal breast tissue (P = 0.01). This was accounted
      for by an increase in Ca(2+)-dependent PKC activity (P = 0.01), there being no
      significant increase in Ca(2+)-independent PKC activity. These data suggest that
      the activities of both PKA and PKC signalling pathways are intrinsically higher
      in malignant compared with normal breast tissue and these may therefore represent
      targets for interventive treatment of breast cancer.

PMID- 9014756
TI  - Induction of metalloproteinase (MMP1) expression by epidermal growth factor (EGF)
      receptor stimulation and serum deprivation in human breast tumour cells.
AB  - The levels of the matrix metalloproteinase MMP1 mRNA in three breast tumour cell
      lines with varying numbers of epidermal growth factor (EGF) receptors, MDA-MB
      231, T47D and MCF7, were investigated following treatment with EGF or TGF alpha
      in serum-free medium for up to 24 h. A higher level of MMP1 mRNA was found in
      both control and treated MDA-MB-231 cells compared with the other two cell lines.
      A 2-fold increase in MMP1 transcripts was observed in MDA-MB-231 cells following
      a 30 min treatment with EGF and 2 h with TGF alpha. An increase in MMP1
      transcripts following serum deprivation in the absence of growth factor
      stimulation was also seen. This effect was not evident with the other cell lines.
      In MDA-MB-231 cells, low concentrations of MMP1 protein were detected in medium
      from treated cells and was only significantly increased after 24 h but it was
      inhibited by cycloheximide. The early effect of EGF on MMP1 expression was not
      inhibited by cycloheximide. Treatment with cycloheximide for longer periods
      produced increased transcripts of MMP1, TGF alpha and EGF-receptor, suggesting
      the activation of processes for tissue breakdown and subsequent repair may occur
      on prolonged inhibition of protein synthesis. These results confirm a
      relationship between EGF-receptor stimulation and MMP1 expression in some EGF
      receptor positive tumour cells, which, in part, occurs at the transcriptional
      level, and have implications for the invasive progression of EGF-receptor
      positive tumours particularly in areas of nutritional deprivation.

PMID- 9014757
TI  - Rapid recovery of a functional MDR phenotype caused by MRP after a transient
      exposure to MDR drugs in a revertant human lung cancer cell line.
AB  - Prior studies have shown that, in some human tumour cells, increased expression
      of the multidrug resistance gene MDR1 can be induced in response to certain
      stress conditions such as a transient exposure to cytotoxic agents. Little is
      known about the possibility of increasing the expression of the recently cloned
      multidrug resistance-associated protein (MRP) in response to a transient exposure
      to cytotoxic drugs. In order to examine this possibility, we have used sensitive
      assays (RT-PCR, flow cytometry) and the sensitive large cell lung cancer cell
      line, COR-L23/P, and the revertant line (COR-L23/Rev), generated by growing the
      doxorubicin-selected, MRP-overexpressing resistant variant COR-L23/R without drug
      exposure for 24-28 weeks. COR-L23/Rev overexpresses MRP, but to a lesser extent
      than COR-L23/R. COR-L23/Rev rapidly recovered similar levels of MRP mRNA, protein
      expression, resistance and drug accumulation deficit as COR-L23/R after a 48-72 h
      exposure to cytotoxic concentrations of doxorubicin or vincristine but not
      cisplatin. The increase in MRP mRNA could only be detected 3 to 4 days after the
      transient exposure to drugs. However, when the parental line, COR-L23/P, was
      exposed to equitoxic doses of doxorubicin, vincristine or cisplatin, no increase
      in the levels of MRP mRNA could be observed at higher doses (5- to 10-fold the
      IC50) of doxorubicin or vincristine (but not of cisplatin), we detected a
      transient increase in the levels of MDR1 mRNA immediately after short-term
      exposure. In conclusion, we have shown that a human revertant lung cancer cell
      line (COR-L23/Rev) has the ability to recover quickly, similar levels of MRP
      expression and resistance as COR-L23/R after a transient exposure to the MDR
      drugs doxorubicin and vincristine.

PMID- 9014758
TI  - Detection of interleukin-8 mRNA and protein in human colorectal carcinoma cells.
AB  - Interleukin-8 (IL-8) is a member of the chemokine family of pro-inflammatory
      chemotactic cytokines and is secreted by some human colorectal carcinoma cell
      lines. We have used in situ hybridisation and immunohistochemistry to determine
      whether IL-8 mRNA and protein, respectively, are produced by human colorectal
      carcinoma cells in vivo. IL-8 mRNA was detected within the cytoplasm of tumour
      cells in all nine samples tested, including that of a tumour which had
      metastasised to a lymph node. Non-involved colonic mucosa within the same tissue
      blocks showed much weaker labelling. IL-8 protein was detected in 74% (23/31) of
      tumour samples and was mainly localised to the tumour cell cytoplasm. In 30% of
      cases, staining was heterogeneous, with between 1 and 30% of cells being
      positive. In some tumour cells, IL-8 showed a perinuclear distribution resembling
      that found by in situ hybridisation. Some infiltrating leucocytes, endothelial
      cells and fibroblast-like cells within the tumour sections were also positive for
      IL-8 mRNA and protein. The possibilities that colorectal tumours produce IL-8 to
      aid invasion and/or metastasis or as a tumour growth factor are discussed.

PMID- 9014759
TI  - The cellular interaction of 5-fluorouracil and cisplatin in a human colon
      carcinoma cell line.
AB  - The combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been shown to
      have synergistic cytotoxicity in human tumours, but the biochemical mechanism for
      this interaction remains unclear. Therefore, the aim of this study was to
      investigate the interaction of 5-FU and CDDP in a human colon carcinoma cell
      line, NCI H548. A 24 h exposure to 5-FU resulted in a 5-FU IC50 value of 24.2 +/-
      4.5 microM, Dm 22.6 microM; exposure to CDDP for 2 h resulted in a IC50 value of
      20.8 +/- 8.0 microM, Dm 21.9 microM. When cells were exposed simultaneously to 5
      FU for 24 h and CDDP for the initial 2 h, or when cells were treated with CDDP
      for 2 h followed by various concentrations of 5-FU for 24 h, no greater than
      additive cytotoxicity was observed. In contrast, when cells were treated with 5
      FU for 24 h prior to CDDP for 2 h, a greater than additive interaction was noted
      (5-FU IC50 1.2 +/- 0.6 microM, Dm 1.3 microM, CI 0.45). Thymidine 10 microM
      partially reversed the growth inhibitory effects of the 5-FU/ CDDP combination.
      Using both immunological and biochemical assays, no notable differences in the
      total amount of TS enzyme or the fraction of bound TS enzyme could be detected in
      the absence or presence of CDDP. No notable differences could be detected in
      intracellular reduced folate pools, FdUMP or FUTP pools, or 5-FU incorporation
      into RNA or DNA with the addition of CDDP to 5-FU. DNA fragmentation studies
      revealed that the combination of 5-FU followed by CDDP demonstrated a greater
      degree of single-stranded DNA fragments in parental (P = 0.024) and newly
      synthesised DNA (P = 0.025) compared with the administration of CDDP prior to 5
      FU or either drug alone. The increase in smaller DNA fragment size was reversed
      with the addition of thymidine (10 microM). These findings suggest that the
      interaction of 5-FU and CDDP is associated with a greater degree of fragmentation
      of both nascent and parental DNA.

PMID- 9014760
TI  - Human antibodies against the polymorphic epithelial mucin in ovarian cancer
      patients recognise a novel sequence in the tandem repeat region.
AB  - The humoral immune response to the polymorphic epithelial mucin (PEM) was studied
      by characterising the reactivity of human antibodies generated by EBV
      immortalised B-cells from tumour-draining lymph nodes of ovarian cancer patients.
      All the human antibodies, selected in ELISA for their reactivity to the protein
      tandem core repeat sequence, reacted with PEM-expressing tumour cells. Aberrant
      glycosylation of the peptide core of the PEM molecule in cancer cells leads to
      the exposure of peptide epitopes that can be considered tumour specific. The
      epitope mapping of six human antibodies revealed that only one of them contained
      the PDTR sequence, shown to be the immunodominant epitope in the mouse. Four of
      the six human antibodies recognised a novel common immunogenic sequence (APPAH)
      in the tandem repeats. The binding of these human antibodies did not appear to be
      modulated by the length of the carbohydrate side chains, as shown by O
      glycosylation inhibition studies. These results indicate that distinct sequences
      within the tandem repeat of PEM are target for a humoral immune response in
      humans. The presence of antibodies directed against different epitopes within the
      same antigenic region may modulate the antigen presentation process and the
      ongoing immune response. This data may help in clarifying the mechanisms of the
      immune response to PEM in cancer patients for the development of PEM-based
      immunotherapy.

PMID- 9014761
TI  - Tunicamycin potentiates drug cytotoxicity and vincristine retention in multidrug
      resistant cell lines.
AB  - Tunicamycin (TM), an inhibitor of glycoprotein processing, was investigated for
      its potential to reverse the multiple drug resistance (MDR) phenotype. When TM
      was added in vitro to drug-resistant NIH-3T3-MDR and KB-8-5-11 cells, they
      developed an increased sensitivity to doxorubicin, epirubicin, vincristine and
      colchicine. Similarly, the sensitivity of NIH-3T3-MDR cells to cisplatin was also
      enhanced by TM. In the presence of TM, drug-sensitive NIH-3T3-parental cells
      exhibited greater susceptibility to the toxic effects of doxorubicin, epirubicin,
      vincristine (marginally significant), and colchicine, but not to cisplatin.
      Tunicamycin-treated drug-sensitive KB-3-1 cells showed an increased response to
      vincristine, but not to the other anticancer drugs. Pretreatment with TM
      inhibited glycoprotein synthesis in all the cell lines. Neither prior exposure
      to, nor co-incubation with TM, influenced the uptake of vincristine (VCR) in the
      various cell lines. However, NIH-3T3-MDR cells accumulated less VCR than their
      drug-sensitive controls and also exhibited reduced efflux of the drug when
      treated with TM. There were no significant differences in the levels of
      intracellular VCR uptake between drug-sensitive KB-3-1 and KB-8-5-11 cells.
      Tunicamycin increased intracellular VCR retention in KB-8-5-11 and NIH-3T3-MDR
      cells, but not in NIH-3T3-parental cells. However, drug-sensitive KB-3-1 cells
      expressed reduced VCR retention in response to TM exposure, indicating that
      correlations between VCR toxicity and its retention in the presence of TM should
      be made with caution. The results suggest that the enhancement of intracellular
      VCR retention in MDR cells lines caused by TM is likely to be the result of
      inhibition of VCR efflux. Inhibition of glycoprotein synthesis during TM exposure
      may account for the changes in VCR efflux and retention observed in the MDR cell
      lines. The enhancement of cisplatin cytotoxicity in NIH-3T3-MDR cells after
      exposure to TM is an interesting observation, since it is generally believed that
      agents which modify the MDR phenotype do not show a sensitising effect to
      cisplatin. These findings may have applications in the reversal of drug
      resistance.

PMID- 9014762
TI  - Possible deleterious effect of tamoxifen in premenopausal women with locoregional
      recurrence of breast cancer.
AB  - Tamoxifen (TAM) treatment following isolated locoregional recurrence of breast
      cancer significantly increases 5-year disease-free survival rates compared with
      observation alone in potentially hormone-responsive patients [J Clin Oncol 1994,
      12, 2071-2077]. The treatment outcome was re-analysed by menopausal status
      (stratification factor) in 35 premenopausal and in 132 postmenopausal patients.
      Disease progression was highly reduced by tamoxifen in the postmenopausal group
      and was similar to control in the premenopausal group. However, the 5-year
      cumulative incidence analysis of the type of first failure showed TAM to be
      associated with increased incidence of distant metastases (P = 0.01) in
      premenopausal patients. TAM reduced local progression (P = 0.40) in premenopausal
      and both types of failure (P = 0.16 and P = 0.001, respectively) in
      postmenopausal patients. Administration of TAM was associated with a decrease of
      5-year overall survival from 90 +/- 7% to 60 +/- 14% in premenopausal patients.
      Although cautious interpretation of these results is highly recommended due to
      the small patient numbers and the retrospective subset analyses, these findings
      might be worthy of further investigation in larger trials. Prospective randomised
      studies to test hormonal treatment outcome by menopausal status should be
      encouraged in breast cancer.

PMID- 9014763
TI  - Interstitial pneumopathy after mantle field irradiation for Hodgkin's disease.
AB  - This retrospective analysis was undertaken to determine the incidence of
      interstitial pneumopathy and the clinical course after mantle field irradiation
      for Hodgkin's disease focusing on the role of radio- and chemotherapy. 136
      patients were evaluable, 40 having received radiotherapy only and 96 patients
      having received combined radio-chemotherapy. The median follow-up time was 21.5
      months. The overall incidence was 19%; 4 patients died of severe interstitial
      pneumopathy and 3 died of simultaneous severe complications. The radiation dose
      was correlated with the incidence of interstitial pneumopathy (P = 0.0021).

PMID- 9014764
TI  - Comments on the Role of reproductive and menstrual factors in cancer of the
      breast before and after menopause, Talamini et al., Eur J Cancer, 32A, no. 2, pp.
      303-310, 1996.

PMID- 9014765
TI  - p21WAF1 and p53 immunohistochemical expression in breast carcinoma may predict
      therapeutic response to adjuvant treatment.

PMID- 9014766
TI  - Is the time interval between diagnosis and radiation treatment an important
      factor in brain metastases?

PMID- 9014767
TI  - Malignant lymphoma with severe hypoglycaemia.

PMID- 9014768
TI  - Incidence of inflammatory bowel disease across Europe: is there a difference
      between north and south? Results of the European Collaborative Study on
      Inflammatory Bowel Disease (EC-IBD).
AB  - BACKGROUND: It has been suggested that the incidence of inflammatory bowel
      disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD),
      is three or more times higher in northern than in southern Europe. The aim of
      this EC funded study was to investigate this apparent variation by ascertaining
      the incidence of IBD across Europe. METHODS: For the period 1 October 1991 to 30
      September 1993 all new patients diagnosed with IBD were prospectively identified
      in 20 European centres according to a standard protocol for case ascertainment
      and definition. FINDINGS: Altogether 2201 patients aged 15 years or more were
      identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD,
      and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years
      (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI)
      7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern
      centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI
      1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For
      UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and
      for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north
      west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada
      (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west
      Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the
      age specific incidence of UC in men and women with the incidence in women but not
      men declining with age. INTERPRETATION: The higher overall incidence rates in
      northern centres did not seem to be explained by differences in tobacco
      consumption or education. Nevertheless, the magnitude of the observed excess for
      both conditions is less than expected on the basis of previous studies. This may
      reflect recent increases in the incidence of IBD in southern Europe whereas those
      in the north may have stabilised.

PMID- 9014770
TI  - Cytokine gene polymorphisms in inflammatory bowel disease.
AB  - BACKGROUND: Concordance rates in siblings and twins provide strong evidence that
      genetic susceptibility is important in the pathogenesis of inflammatory bowel
      disease. The number and identity of susceptibility genes is largely uncertain.
      Cytokine genes are attractive candidate loci. AIMS: To study allelic frequencies
      of polymorphisms of the interleukin-1 receptor antagonist (IL-1RA) gene and the
      tumour necrosis factor alpha gene in patients with inflammatory bowel disease.
      SUBJECTS: One hundred and twenty nine North European caucasoid patients with
      ulcerative colitis, 120 patients with Crohn's disease, and 89 healthy controls.
      METHODS: Genotyping was performed by polymerase chain reaction. A variable number
      of tandem repeats (VNTR) in the IL-1RA gene and a single base pair polymorphism
      in the TNF alpha gene promoter region (TNF-308) were analysed. RESULTS: No
      significant differences in IL-1RA VNTR allelic frequencies were noted between
      Crohn's disease (allele 1: 72.6%, allele 2: 24.7%, allele 3: 2.6%), ulcerative
      colitis (72.6%, 24.3%, 3.1%, respectively), and controls (76.9%, 20.8% and 2.3%).
      Some 42.4% of patients with ulcerative colitis and 43.4% patients with Crohn's
      disease were carriers of allele 2, compared with 34.8% healthy subjects. The TNF2
      allele was modestly reduced in Crohn's disease (13.2%), compared with healthy
      subjects (21.3%; p = 0.04), and ulcerative colitis (21.6%). CONCLUSIONS: The
      associations demonstrated are modest: these polymorphisms are unlikely to be
      important determinants of overall disease susceptibility.

PMID- 9014769
TI  - Phospholipase A2 activating protein and idiopathic inflammatory bowel disease.
AB  - BACKGROUND: Crohn's disease and ulcerative colitis are idiopathic inflammatory
      bowel diseases (IBD) involving synthesis of eicosanoids from arachidonic acid
      (AA), which is released from membrane phospholipids by phospholipase A2 (PLA2). A
      potentially important regulator of the production of these mediators is a protein
      activator of PLA2, referred to as PLA2 activating protein (PLAP). AIMS: The
      purpose of this investigation was to discover if PLAP values might be increased
      in the inflamed intestinal tissue of patients with IBD and in intestinal tissue
      of mice with colitis. PATIENTS: Biopsy specimens were taken from patients with
      ulcerative colitis and Crohn's disease undergoing diagnostic colonoscopy, and
      normal colonic mucosa was obtained from patients without IBD after surgical
      resection. METHODS: Immunocytochemistry with affinity purified antibodies to PLAP
      synthetic peptides was used to locate PLAP antigen in sections of intestinal
      biopsy specimens from IBD patients compared with that of normal intestinal
      tissue. Northern blot analysis with a murine [32P] labelled plap cDNA probe was
      performed on RNA extracted from the colons of mice fed dextran sulphate sodium
      (DSS) and cultured HT-29 cells exposed to lipopolysaccharide (LPS). RESULTS: PLAP
      antigen was localised predominantly within monocytes and granulocytes in
      intestinal tissue sections from IBD patients, and additional deposition of
      extracellular PLAP antigen was associated with blood vessels and oedema fluid in
      the inflamed tissues. In contrast, tissue sections from normal human intestine
      were devoid of PLAP reactive antigen, except for some weak cytoplasmic reaction
      of luminal intestinal epithelial cells. Similarly, colonic tissue from DSS
      treated mice contained an increased amount of PLAP antigen compared with
      controls. The stroma of the lamina propria of the colonic mucosa from the DSS
      treated mice reacted intensely with antibodies to PLAP synthetic peptides, while
      no reaction was observed with control mouse colons. These data were supported by
      northern analysis which showed that PLAP mRNA was increased in the colons of DSS
      treated mice and cultured HT-29 cells exposed to LPS. CONCLUSIONS: As PLAP values
      were increased in the intestinal mucosa of IBD patients and mice with colitis, as
      well as in LPS treated cultured HT-29 cells, a role was postulated for PLAP in
      increasing PLA2 activity, which leads to the increased synthesis of eicosanoids
      in intestinal tissues of patients with these inflammatory diseases.

PMID- 9014771
TI  - Detection of adenocarcinoma in Barrett's oesophagus by means of laser induced
      fluorescence.
AB  - PATIENTS: Seven patients with Barrett's metaplastic epithelium and oesophageal
      adenocarcinoma were investigated by means of laser induced fluorescence after low
      dose intravenous injection (0.35 mg/kg bw) of Photofrin (QLT, Vancouver, Canada).
      Laser induced fluorescence measurements were performed immediately after
      resection of the oesophagus. METHODS: Laser induced fluorescence spectra were
      recorded from 15-30 locations in each surgical specimen from normal mucosa,
      Barrett's epithelium, and tumour tissue. Histological examination was performed
      on each location to correlate the fluorescence spectral characteristics with
      histological status of the epithelium (normal, metaplastic or malignant).
      Measurements were also performed during endoscopy in five patients to test the
      applicability of the method in a clinical setting. Fluorescence spectra were
      recorded and evaluated at characteristic wavelengths, and biopsy specimens were
      collected. Fluorescence ratios were calculated as the quotient of Photofrin
      fluorescence divided by autofluorescence. RESULTS: The mean (SD) fluorescence
      ratio values were 0.10 (0.058) for normal oesophageal mucosa, 0.16 (0.073) for
      normal gastric mucosa, 0.205 (0.17) for Barrett's epithelium with moderate
      dysplasia, 0.79 (0.54) for severe dysplasia, and 0.78 (0.56) for adenocarcinoma.
      The highest fluorescence ratios were obtained for adenocarcinoma tissue, which
      could generally be distinguished from all nonmalignant tissue. Metaplastic
      Barrett's epithelium also yielded higher fluorescence ratios than did normal
      mucosa. CONCLUSIONS: The results suggest that the technique can be used during
      endoscopy for real time tissue characterisation in the oesophagus, as an aid in
      detecting malignant transformation not macroscopically apparent at endoscopy.

PMID- 9014772
TI  - Identification of carcinoembryonic antigen-producing cells circulating in the
      blood of patients with colorectal carcinoma by reverse transcriptase polymerase
      chain reaction.
AB  - BACKGROUND: Application of the reverse transcriptase polymerase chain reaction
      (RT-PCR) to identification of circulating tumour cells in colorectal cancer.
      AIMS: To assess whether circulating malignant cells in patients with colorectal
      liver metastasis could be identified by RT-PCR recognition of mRNA coding for the
      tumour marker carcinoembryonic antigen (CEA). PATIENTS: A total of 31 with
      colorectal liver metastases and 22 no-cancer controls. METHODS: Specific cDNA
      primers for CEA transcripts were used to apply RT-PCR to tissue biopsy specimens,
      colon carcinoma cell lines, and peripheral blood samples from patients with
      colorectal liver metastases. A strongly CEA-expressive HT115 colorectal carcinoma
      cell line was used to spike blood samples from no-cancer control subjects.
      RESULTS: The limit for detection of CEA cDNA by Southern blotting using HT115
      cells was 50 cells per 14 ml of spiked blood. There was a significant difference
      (p = 0.007) in RT-PCR positive expression between patients with liver metastasis
      (26/31) compared with controls (5/22). There was no significant relation between
      the prevalence of CEA cDNA amplification and serum CEA level or metastasis volume
      in patients with liver metastasis. CONCLUSIONS: This is the first study to
      suggest that identification of circulating colorectal cancer cells using RT-PCR
      for detection of CEA cDNA is feasible.

PMID- 9014773
TI  - Comparison of three faecal occult blood tests in the detection of colorectal
      neoplasia.
AB  - METHODS AND AIMS: For the detection of colorectal neoplasia, 192 consecutive
      patients had colonoscopy to evaluate the sensitivity and specificity of three
      faecal occult blood tests (FOBT). Of 160 evaluable patients (96 female, mean age
      51.9), 21 patients (13.1%) had adenomas and three patients (1.9%) had colorectal
      carcinoma. RESULTS: When comparing all three faecal occult blood tests for the
      detection of colorectal neoplasia, the sensitivity of Monohaem (43.8%) was
      superior to both Hemoccult II (25%) and to BM-Test colon albumin (25%). The
      specificity of Monohaem (94.6%) was greater than both Hemoccult II (88%) and BM
      Test colon albumin (89%). Using McNemar's test, Monohaem was a more accurate FOBT
      than Hemoccult II and BM-Test albumin (p < 0.05). In the 21 patients with
      adenomatous polyps, FOBT sensitivity seemed to be dependent on polyp size, but
      not polyp site. CONCLUSIONS: Monohaem, a feacal occult blood test that uses a
      monoclonal antibody that is specific for human haemoglobin, is a more accurate
      test in the detection of colorectal neoplasia and should possibly be used in
      colorectal cancer screening programmes.

PMID- 9014774
TI  - Laser and brachytherapy in the palliation of adenocarcinoma of the oesophagus and
      cardia.
AB  - BACKGROUND: Palliation of malignant dysphagia is possible by a variety of methods
      although all have significant drawbacks. Laser therapy is an effective and safe
      treatment but has to be repeated at four to five weekly intervals to maintain
      palliation. A means of augmenting the benefits while reducing the need for repeat
      treatments would be highly beneficial to these patients. AIMS: To prospectively
      explore the safety and efficacy of intraluminal radiotherapy (brachytherapy) when
      used to augment laser recanalisation for malignant dysphagia. PATIENTS: Nineteen
      patients with dysphagia due to advanced adenocarcinoma of the oesophagus or
      cardia were recruited. METHODS: All patients received laser recanalisation until
      able to swallow a soft diet or better, before the application of a single dose of
      brachytherapy (10 Gy at 1 cm from the source). Patients were followed up and
      treated promptly by further endoscopic means in the event of their dysphagia
      worsening. RESULTS: Six patients (32%) required no further treatment until death
      at a median of 10 weeks (range 1-20 weeks). Further therapy was required at a
      median of 11 weeks (range 4-37 weeks) after brachytherapy for those 13 patients
      with recurrent dysphagia. Subsequent symptom control required endoscopic
      intervention at an average of once every nine weeks. There was no mortality
      associated with laser or brachytherapy. Median survival from initial treatment
      and including the one survivor was 36 weeks (range 5-132 weeks). CONCLUSIONS:
      Laser plus brachytherapy offers a safe and effective means of palliating
      malignant dysphagia due to adenocarcinoma, with a longer dysphagia free interval
      than historical controls treated with laser alone.

PMID- 9014775
TI  - Dietary folate protects against the development of macroscopic colonic neoplasia
      in a dose responsive manner in rats.
AB  - BACKGROUND AND AIMS: Diminished folate status is associated with enhanced
      colorectal carcinogenesis. This study investigated the potential chemopreventive
      role of dietary folate in the dimethylhydrazine colorectal cancer model. SUBJECTS
      AND METHODS: Sprague-Dawley rats were fed diets containing either 0, 2 (daily
      dietary requirement), 8 or 40 mg folate/kg diet for 20 weeks. After five weeks of
      diet, rats were injected with dimethyl-hydrazine (44 mg/kg) weekly for 15 weeks.
      Fifteen weeks after the first injection of dimethylhydrazine, all rats were
      killed. Folate status was determined, and the entire colorectum from each rat was
      analysed for macroscopic and microscopic neoplasms. RESULTS: Plasma and colonic
      folate concentrations correlated directly with dietary folate levels (p < 0.005).
      The incidence of microscopic neoplasms was similar among the four groups.
      However, the incidence and the average number of macroscopic tumours per rat
      decreased progressively with increasing dietary folate levels up to 8 mg/kg diet
      (p < 0.05). In the strongly procarcinogenic milieu used in this study, folate
      supplementation at 20 times the basal requirement was associated with rates of
      macroscopic tumour development that were intermediate, and not statistically
      distinct, from rates observed at either 0 or 8 mg/kg diet. CONCLUSIONS: These
      data indicate that in this rat model, (a) increasing dietary folate up to four
      times the basal requirement leads to a progressive reduction in the evolution of
      macroscopic neoplasms from microscopic foci; and (b) folate supplementation
      beyond four times the requirement does not convey further benefit.

PMID- 9014777
TI  - Rapid distal small bowel transit associated with sympathetic denervation in type
      I diabetes mellitus.
AB  - BACKGROUND: The pattern of progression of a meal from the stomach to the caecum
      in diabetes mellitus is controversial and the differential roles of transit
      through the jejunum and the ileum have not been investigated in diabetes. AIMS:
      To determine gastric emptying and transit rates through proximal and distal
      regions of the small bowel in type I diabetic patients. SUBJECTS: The study
      included six diabetic patients with evidence of autonomic neuropathy (DM-AN
      group), 11 diabetics without autonomic dysfunction (DM group), and 15 control
      volunteers. METHODS: Gastric emptying and small bowel transit of a liquid meal
      were evaluated scintigraphically in these subjects. Transit through regions of
      interest corresponding to the proximal and distal small intestine up to the
      caecum was determined and correlated with gastric emptying rates, cardiovascular
      measurements of autonomic function, and the occurrence of diarrhoea. RESULTS:
      Gastric emptying and transit through the proximal small bowel were similar in the
      three groups. The meal arrived to the caecum significantly earlier in DM-AN
      patients (median; range: 55 min; 22-->180 min) than in the DM group (100 min; 44-
      >180 min, p < 0.05) or in controls (120 min; 80-->180 min, p < 0.02).
      Accumulation of chyme in the distal small bowel was decreased in DM-AN patients,
      who showed values for peak activity (30%; 10-55%) significantly lower than in the
      DM group (49%; 25-77%, p = 0.02) and controls (50%; 30-81%, p = 0.02). In DM
      patients (n = 17), the time of meal arrival to the caecum was significantly
      correlated with both orthostatic hypotension (coefficient of contingency, C =
      0.53, p < 0.01) and diarrhoea (C = 0.47, p < 0.05), but not with gastric emptying
      rates. CONCLUSIONS: Patients with type I diabetes mellitus and sympathetic
      denervation have abnormally rapid transit of a liquid meal through the distal
      small bowel, which may play a part in diarrhoea production.

PMID- 9014778
TI  - Effect of distension and feeding on phasic changes in human proximal gastric
      tone.
AB  - BACKGROUND: Proximal stomach by virtue of its property of accommodation acts as a
      reservoir for the ingested food, but its role in emptying and the factors
      modulating it remain unexplored. AIM: To assess the effects of distension and of
      feeding on proximal gastric tone. SUBJECTS: 14 healthy volunteers with no current
      or past history of any gastro-intestinal symptoms. METHODS: Isobaric changes in
      volume of the proximal stomach were recorded both during fasting and for the
      first 30 minutes after a meal. RESULTS: For a given degree of distension, the
      mean (SEM) intragastric pressure was consistently lower, immediately after meal
      ingestion (9.8 (1.1), mm Hg) than during fasting (12.9 (0.6) mm Hg; p < 0.01).
      Proximal gastric tone was continuously variable with a frequency of fluctuation
      of 0.9-1.3/minute and an amplitude of 16.8 (2.2) ml, superimposed upon slower
      higher amplitude fluctuations in baseline tone. These variations in tone were
      unaffected by the degree of gastric distension or by food. CONCLUSIONS: While
      proximal gastric tone decreases after meal ingestions consistent with
      accommodation, the fluctuations in tone are not an importance factor in the
      modulation of nutrient emptying from the proximal stomach in the immediate
      postprandial period.

PMID- 9014776
TI  - Oxytocin increases thresholds of colonic visceral perception in patients with
      irritable bowel syndrome.
AB  - AIM: The effects of oxytocin on colonic perception of intraluminal distension
      were evaluated in 26 patients with irritable bowel syndrome (IBS), using a
      flaccid bag placed in the descending colon and connected to a computerised
      barostat. METHOD: Symptomatic responses (first sensation and pain) were evaluated
      during isobaric distensions (4 mm Hg increments, five minute duration, five
      minute interval with return to zero pressure between each step), performed
      automatically by the barostat, during a continuous infusion of placebo or various
      doses of oxytocin (10, 20, 30, and 50 mU/min). RESULTS: The distension pressure
      (mean (SD)) required to induce a first abdominal sensation was 17.3 (5.5) mm Hg
      on placebo, 19.9 (5.8) on oxytocin 10 mU/min (NS), 22.3 (6.0) mm Hg on oxytocin
      20 mU/min (p < 0.01), 23.1 (6.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 24.0
      (7.1) mm Hg on oxytocin 50 mU/min (p < 0.01). The distension pressure required to
      induce pain was 24.8 (6.3) mm Hg on placebo, 26.0 (5.8) on oxytocin 10 mU/min
      (NS), 33.3 (7.8) mm Hg on oxytocin 20 mU/min (p < 0.01), 34.2 (7.6) mm Hg on
      oxytocin 30 mU/min (p < 0.01), and 34.3 (7.9) mm Hg on oxytocin 50 mU/ min (p <
      0.01). Compliance curves were not different after placebo and oxytocin injection
      at the different doses. Naloxone did not inhibit the effect of oxytocin. Oxytocin
      also did not alter somatic perception, characterised by the RIII reflex at the
      level of the biceps femori. CONCLUSIONS: Oxytocin significantly increases
      thresholds for visceral perception in IBS patients at doses equal or to greater
      than 20 mU/min, possibly by acting at the level of visceral afferents.

PMID- 9014779
TI  - Zonal adult Hirschsprung's disease.
AB  - BACKGROUND: Hirschsprung's disease is a congenital disorder which is rare in
      adulthood. In typical cases the aganglionosis involves mainly the rectum or
      rectosigmoid colon and the lesion starts from the anal valve. Zonal segmental
      aganglionosis is a very rare type even in children. PATIENT: A 54 year old women
      with zonal segmental aganglionosis had an aganglionic segment 18 cm in length
      located in the rectosigmoid colon with an 8 cm long normal appearing rectum and
      dilated proximal colon. Resection of the stenotic segment with end to end
      anastomosis was performed. CONCLUSION: The functional result was excellent five
      years after the operation.

PMID- 9014780
TI  - Helicobacter pylori: is it all in the family?

PMID- 9014781
TI  - Adding interventions to interferon in chronic HCV infections.

PMID- 9014782
TI  - Sensational developments in the irritable bowel.

PMID- 9014783
TI  - Clinical ultrasound examination.

PMID- 9014784
TI  - Diverticular disease.

PMID- 9014785
TI  - Helicobacter pylori and duodenogastric reflux.

PMID- 9014786
TI  - Calcium and colorectal epithelial cell proliferation.

PMID- 9014787
TI  - Emergency endoscopy.

PMID- 9014788
TI  - Closure of the arterial duct: past, present, and future.

PMID- 9014789
TI  - Ethics committees and the treatment of congenital heart disease.

PMID- 9014790
TI  - Leonardo da Vinci (1452-1519).

PMID- 9014791
TI  - Genetic factors in familial hypertrophic cardiomyopathy: does molecular
      cardiology offer new perspectives?

PMID- 9014792
TI  - Spin-echo nuclear magnetic resonance for tissue characterisation in
      arrhythmogenic right ventricular cardiomyopathy.
AB  - OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial
      disorder characterised clinically by ventricular arrhythmias that can cause
      cardiac arrest and morphologically by fatty or fibro-fatty myocardial atrophy of
      the right ventricle. In vivo tissue characterisation without endomyocardial
      biopsy would be useful. The aim of this study was to investigate the diagnostic
      accuracy of spin-echo nuclear magnetic resonance (NMR) for tissue
      characterisation in ARVC. PATIENTS AND METHODS: Twenty three subjects (15 men and
      eight women, aged 18-49, mean 34) were studied with spin-echo T1-weighted NMR and
      multislice scan. Fifteen had a clinical diagnosis of ARVC and eight were controls
      (age and sex matched subjects). Data were independently evaluated by two expert
      observers. RESULTS: In the control group NMR was always negative (100%
      specificity). Ten of the 15 patients with ARVC had an abnormal NMR result (67%
      sensitivity), with areas that had a signal intensity close to that of pericardial
      or subcutaneous fat. In the remaining five cases the NMR signal was inadequate.
      Nine patients underwent both NMR and endomyocardial biopsy; biopsy was positive
      in eight (89%) and NMR was positive in five (56%). CONCLUSIONS: NMR is a useful
      non-invasive diagnostic tool in the evaluation of fatty replacement in ARVC. The
      technique can be used with other procedures in the initial diagnostic evaluation
      and is a useful alternative tool in the long term follow up of patients with
      ARVC.

PMID- 9014793
TI  - Effect of pre-treatment with transdermal glyceryl trinitrate on myocardial
      ischaemia during coronary angioplasty.
AB  - OBJECTIVE: In the light of the reported inconsistent anti-ischaemic and
      antianginal effects of transdermal glyceryl trinitrate, its efficacy and
      influence on the effects of intracoronary glyceryl trinitrate were examined
      during coronary angioplasty, which provides a model of controlled, reversible
      ischaemia. DESIGN: Double blind, randomised study of the effect of transdermal
      and intracoronary glyceryl trinitrate on ischaemia during coronary angioplasty.
      PATIENTS: 40 patients with isolated severe stenosis of the left anterior
      descending coronary artery. INTERVENTIONS: Patients were randomised (double
      blind) to transdermal glyceryl trinitrate (10 mg per day) and placebo, starting
      four to six hours before angioplasty. After 4 one-minute balloon inflations
      intracoronary glyceryl trinitrate was injected (0.2 mg) and then 4 further one
      minute inflations were performed. MAIN OUTCOME MEASURES: The time to angina and
      the time to > 0.2 mV ST shift on surface electrocardiogram (ECG) or intracoronary
      ECG during the individual inflations. RESULTS: These times did not significantly
      differ during initial inflations between transdermal glyceryl trinitrate (27
      (11), 25 (9), and 19 (9) s, respectively) and placebo (34 (11), 30 (8), and 21
      (7) s. After intracoronary glyceryl trinitrate, they were significantly prolonged
      compared with the initial values, without differences between patients with
      transdermal glyceryl trinitrate (37 (10), 30 (8), and 23 (8) s, respectively) or
      placebo (39 (15), 36 (11), and 28 (12) s). Ischaemic preconditioning was not
      seen. CONCLUSIONS: Transdermal glyceryl trinitrate (10 mg per day), unlike
      intracoronary glyceryl trinitrate, did not alleviate the myocardial ischaemia
      produced by balloon inflation during coronary angioplasty.

PMID- 9014794
TI  - Natural variability of transient myocardial ischaemia during daily life: an
      obstacle when assessing efficacy of anti-ischaemic agents?
AB  - OBJECTIVE: To assess the degree of variability of transient myocardial ischaemia
      during daily life in patients with coronary artery disease, which could confound
      the interpretation of trials of the therapeutic effects of anti-ischaemic agents.
      DESIGN: Prospective method evaluation. SETTING: Tertiary referral centre,
      outpatient clinic. PATIENTS: Patients with stable angina, confirmed coronary
      artery disease, and a positive treadmill exercise test for ischaemia. Patients
      were not preselected on the basis of prior documented transient ischaemia during
      ambulatory ST segment monitoring. INTERVENTIONS: A simulated drug-study with 4
      monitoring phases in 16 subjects. To minimise variability in ischaemic activity,
      patients underwent weekly 48 hour ambulatory ST segment monitoring outside
      hospital off all prophylactic therapy on the same weekdays for 4 weeks. MAIN
      OUTCOME MEASURE: Variability in the frequency and duration of transient
      myocardial ischaemia. RESULTS: There was marked variability in both ischaemic
      activity and mean duration of ischaemia in patients with confirmed ischaemia, the
      greatest degree of variability being between patients and from day to day within
      weeks within patients, with a further contribution to variability being noted
      between fortnights within patients. CONCLUSIONS: Despite assessment off all
      therapy and an adequate period of monitoring (48 hours) with small intervals
      between monitoring periods (5 days), marked variability in ischaemic activity was
      noted, and regression towards the mean was clearly shown. Ambulatory ST segment
      monitoring outside hospital is not a reliable method for assessing the
      therapeutic effects of anti-ischaemic agents.

PMID- 9014795
TI  - Contribution of peripheral chemoreceptors to ventilation and the effects of their
      suppression on exercise tolerance in chronic heart failure.
AB  - OBJECTIVES: To assess the contribution of peripheral chemoreceptors to
      ventilation and the effects of continuous inspired oxygen on exercise tolerance
      in chronic heart failure patients. The role of peripheral chemoreceptors in
      mediating hyperpnoea in chronic heart failure is unknown. Hyperoxia is known to
      suppress the peripheral chemoreceptor drive. The magnitude of decrease in
      ventilation with transient inhalations of oxygen thus provides a measure of the
      contribution of the peripheral chemoreceptors to ventilation. SETTING: Tertiary
      specialist hospital. SUBJECTS AND METHODS: Three breaths of 100% oxygen were
      given at rest and also during cycle ergometry at 25 W to 8 healthy controls (age
      52.0 (4.7) (SEM) years) and 13 patients with chronic heart failure (age 60.5
      (2.1) years (P = NS); radionuclide left ventricular ejection fraction 25.5
      (4.3)%). The peripheral chemoreceptor sensitivity was also measured by assessing
      the ventilatory response to hypoxia using transient inhalations of pure nitrogen.
      Another group of 12 patients with chronic heart failure (age 65.5 (1.5) years;
      left ventricular ejection fraction 21.3 (3.0)%) underwent treadmill exercise
      testing on 2 occasions, breathing air or 100% oxygen in a randomised single-blind
      manner, to examine the effects of continuous inspired oxygen on exercise
      tolerance. RESULTS: The reduction in ventilation with transient hyperoxia was
      18.1 (2.9)% v 17.9 (2.6)% (P = NS) at rest and 20.4 (2.8)% v 21.0 (1.6)% (P = NS)
      during cycle ergometry, for controls and patients respectively. The hypoxic
      chemosensitivity was higher in patients (0.232 (0.022) v 0.572 (0.082)
      1/min/%SaO2; P = 0.002). Continuous inspired oxygen increased exercise time (517
      (31) v 455 (27) seconds; P = 0.003), and a trend towards a reduction in the
      ventilatory response to exercise, characterised by the regression slope relating
      ventilation to carbon dioxide output, was evident (31.27 (2.60) v 34.19 (2.35); P
      = 0.08). CONCLUSIONS: Despite an increased peripheral chemoreceptor sensitivity,
      the proportionate contribution of peripheral chemoreceptors to ventilation
      remained similar in heart failure patients (about 20%). This suggests that the
      peripheral chemoreceptors are not the main mediator of increased ventilation and
      there are other non-peripheral chemoreceptor-mediated mechanisms involved.
      Hyperoxia reduced ventilation at rest and during cycle ergometry. The increase in
      exercise duration with continuous inspired oxygen that was associated with a
      reduction in exercise ventilatory response suggests that suppression of the
      peripheral chemoreceptors may improve exercise tolerance; the effects of possible
      reduced skeletal muscle anaerobiosis cannot be excluded, however.

PMID- 9014796
TI  - Effects of increasing flow rate on aortic stenotic indices: evidence from
      percutaneous transvenous balloon dilatation of the mitral valve in patients with
      combined aortic and mitral stenosis.
AB  - OBJECTIVES: To investigate the effects of transvalvar flow rate on aortic valve
      resistance and valve area after percutaneous transvenous balloon dilatation of
      the mitral valve in a homogeneous group of patients with rheumatic heart disease.
      DESIGN: Retrospective analysis of 12 patients with combined aortic and mitral
      stenosis who had undergone balloon dilatation of the mitral valve over a period
      of 9 years. SETTING: Tertiary referral centre. PATIENTS: Twelve (8 women, 4 men;
      mean (SD) age 37 (9) of 227 consecutive patients with critical mitral stenosis
      undergoing transvenous balloon dilation of the mitral valve in the centre also
      had aortic stenosis, defined as a transaortic pressure gradient of more than 25
      mm Hg measured at a catheterisation study before valvuloplasty. INTERVENTIONS:
      Echocardiographic variables (mitral valve area measured by the pressure half-time
      method and planimetry, and the aortic valve area derived from the continuity
      equation) and haemodynamic measurements (cardiac output, left ventricular mean
      systolic pressure, aortic mean pressure, transaortic valve pressure gradient,
      mitral valve and aortic valve areas derived from the Gorlin formula, and aortic
      valve resistance) were assessed before and after transvenous balloon dilatation
      of the mitral valve. Follow up catheterisation to measure haemodynamic variables
      was performed one week after mitral valvuloplasty. RESULTS: Mean transaortic flow
      rate increased 33% after mitral valvuloplasty (from 198 (68) to 254 (41) ml/s, P
      = 0.002). Aortic valve areas derived from the Gorlin formula were significantly
      increased from 0.57 (0.12) to 0.73 (0.14) cm2 (P = 0.006) after mitral
      valvuloplasty. However, aortic valve area and valve resistance derived from the
      continuity equation were independent of the increase in flow rate after mitral
      valvuloplasty (from 1.29 (0.35) to 1.30 (0.29) cm2 and from 317 (65) to 259 (75)
      dyn.s.cm-5, both P = NS). CONCLUSION: The Gorlin-derived aortic valve area tends
      to be flow-dependent, and continuity equation-derived aortic valve area and
      catheterisation-derived valve resistance seem to be less flow-dependent. In
      patients with combined mitral and aortic stenosis, these flow-independent indices
      are important for decision-making.

PMID- 9014797
TI  - Effects of incoordination on left ventricular force-velocity relation in aortic
      stenosis.
AB  - OBJECTIVE: Tension development is often incoordinate in the hypertrophic left
      ventricle (LV). The present study aimed to elucidate the possible effects of
      incoordination on standard LV force-velocity relations in patients with aortic
      stenosis (AS). DESIGN: Prospective study during aortic valve replacement with
      transoesophageal cross sectionally guided M mode echocardiogram, combined with
      high-fidelity LV pressure recorded by pressure transducer tip catheter, and
      thermodilution cardiac output. SETTING: Tertiary cardiac referral centre.
      PATIENTS: 37 patients (mean (SD) age 63 (12)) years were studied before and 20
      hours after aortic valve replacement. MAIN OUTCOME MEASURES: LV function was
      assessed regionally by peak velocity of circumferential fibre shortening (peak
      Vcf), mean systolic wall stress, and peak myocardial power; and globally by LV
      stroke work index. LV coordination was quantified as cycle efficiency, derived
      from LV pressure-dimension loop (lower normal limit > or = 76%). RESULTS: 22
      patients with a coordinate LV had significantly higher peak Vcf (1.85 (0.47) v
      1.46 (0.64) s-1) peak myocardial power (20.8 (8.5) v 12.0 (6.1) mW.cm-3) and
      global stroke work index (440 (155) v 325 (150) mJ.m-2) than those of 15 patients
      with an incoordinate ventricle, all P < 0.05; though there was no significant
      difference in LV end diastolic dimension, mean systolic wall stress, LV mass
      index, or the incidence of coronary artery disease (P > 0.05, respectively).
      Furthermore, when contraction was coordinate, mean systolic circumferential wall
      stress correlated inversely with peak Vcf (r = - 0.71) and positively with peak
      myocardial power (r = 0.83), both P < 0.01. When contraction was incoordinate,
      these correlations did not apply; instead peak Vcf (r = 0.65) and peak myocardial
      power (r = 0.73) both correlated positively with cycle efficiency (P < 0.02 and
      0.01, respectively). By 20 hours after surgery, values of cycle efficiency, peak
      Vcf, and myocardial power were indistinguishable in the previously coordinate and
      incoordinate groups. CONCLUSIONS: In aortic stenosis, incoordination causes a
      fall in LV peak Vcf proportional to the increase in systolic wall stress, and
      thus modifies the standard LV force-velocity relation to mimic depressed
      contractility. However, incoordination and subsequent ventricular dysfunction
      were largely reversible once the aortic stenosis had been relieved.

PMID- 9014798
TI  - Percutaneous balloon dilatation of the atrial septum: immediate and midterm
      results.
AB  - OBJECTIVES: To assess the effectiveness of atrial septostomy by percutaneous
      balloon dilatation in patients with congenital heart defects or primary pulmonary
      hypertension. PATIENTS AND DESIGN: Twenty three patients (15 boys, eight girls;
      aged 10 days to 10 years; 17 with congenital heart defects and six with primary
      pulmonary hypertension), all haemodynamically unstable under optimal medical
      treatment, underwent atrial septostomy by percutaneous balloon dilatation.
      INTERVENTIONS: The balloon catheter entered the left atrium through a patent
      foramen ovale (n = 14) or via transseptal puncture in cases with an intact atrial
      septum (n = 9). The size of the balloons used ranged from 13 to 18 mm. RESULTS:
      There were no complications. The interatrial communication (mm) increased (P <
      0.05) after dilatation and remained unchanged (P = NS) during a 16.6 (13.8) month
      follow up (2 (1.7) v 8.8 (1.4) v 8.2 (1.1), respectively). Transatrial gradient
      (mm Hg) fell and arterial oxygenation (%) improved both in patients with
      transposition (6.3 (0.8) v 0.8 (1) (P = 0.0001) and 40.6 (4.2) v 76.5 (4.8) (P =
      0.0001), respectively) and in those with mitral atresia (13.4 (1.9) v 2 (1.4) (P
      = 0.0001) and 77.1 (3.9) v 81.5 (4.2) (P = 0.008), respectively). There were two
      failures, one early and one late, both in the group of patients with mitral
      atresia or stenosis. A decrease in arterial oxygenation (94.8 (1.5) v 83 (2.4), P
      = 0.004) and an increase in left atrial pressure (6.8 (0.9) v 8.3 (1.2), P =
      0.02) and cardiac index (2.3 (0.2) v 3.1 (0.2) l/min/m2, P = 0.002) was observed
      in patients with primary pulmonary hypertension. CONCLUSIONS: Percutaneous
      balloon dilatation is an effective and safe procedure for creating an adequate
      interatrial communication that can be used as an alternative to blade septostomy.

PMID- 9014799
TI  - Fludrocortisone in the treatment of hypotensive disorders in the elderly.
AB  - OBJECTIVE: To evaluate tolerance of fludrocortisone in older patients with
      hypotensive disorders. DESIGN: Prospective case series. SETTING: Syncope clinic.
      PATIENTS: 64 Consecutive patients over 65 years (mean age 80 years) with one or
      more hypotensive disorders (orthostatic hypotension, vasodepressor carotid sinus
      syncope, and/or vasodepressor neurocardiogenic syncope. INTERVENTIONS:
      Fludrocortisone in daily doses of 100 micrograms [corrected] (72%), 50 micrograms
      [corrected] (27%), and 200 micrograms [corrected] (one patient). MAIN OUTCOME
      MEASURES: Adverse events, treatment withdrawal. RESULTS: During follow up 13
      patients died of unrelated causes. Of the remainder 33% discontinued
      fludrocortisone at a mean of five months. Reasons for discontinuing treatment
      were hypertension, five; cardiac failure, four; depression, three; oedema, three;
      and unspecified, two. In those who continued treatment supine systolic and
      diastolic blood pressure did not differ significantly from baseline (follow up
      two to 21 months). Hypokalaemia developed in 24% at a mean of eight months; in no
      case was treatment withdrawn because of hypokalaemia. CONCLUSION:
      Fludrocortisone, even in low doses, is poorly tolerated in the long term in older
      patients with hypotensive disorders.

PMID- 9014800
TI  - Welder identity, weld date, and the risk of outlet strut fracture in Bjork-Shiley
      convexo-concave valves: the Dutch cohort study.
AB  - OBJECTIVE: To establish whether there is an association between subsequent
      fracture of the outlet strut and welder identity and the weld date of Bjork
      Shiley convexo-concave (BScc) valves. DESIGN: Cohort study. PATIENTS: All Dutch
      BScc valve recipients (n = 2266). MEAN OUTCOME MEASURES: Documented outlet strut
      fracture during follow up. RESULTS: Weld dates were known for 97.0% of all BScc
      valves (n = 2534) implanted in Dutch patients (n = 2266) and welder identity was
      known for 52.2%. During a mean follow up of 9.4 years, 46 fractures were
      documented. For 60 degrees valves welded from 1981 to 1984 the fracture rate
      (0.22 per 100 person-years (95% CI 0.13 to 0.34)) was higher than that for valves
      welded before 1981 (0.04 (95% CI 0.01-0.10)). When all fracture related risk
      factors were taken into account, fracture rates per welder did not show any
      statistically significant differences. CONCLUSIONS: Welder identity does not
      contribute to the risk of strut fracture. Other factors in the production of BScc
      valves may explain the increased risk for valves welded from 1981 to 1984.

PMID- 9014802
TI  - Total UK multi-centre experience with a novel arterial occlusion device (Duct
      Occlud pfm).
AB  - OBJECTIVE: To report the total UK multicentre experience of a novel arterial
      occlusion device (Duct Occlud pfm). DESIGN: Descriptive study of selected non
      randomised paediatric patients with a variety of aortopulmonary connections.
      SETTING: Five UK tertiary referral centres for congenital heart disease. PATIENTS
      AND METHODS: Between March 1994 and February 1995, 57 children aged 2 weeks to 14
      years (median 50 months) underwent attempted closure of their aortopulmonary
      connection. Fifty one had persistent arterial ducts and 9 of them had had a
      Rashkind umbrella device implanted. Five patients had superfluous modified
      Blalock-Taussig shunts (mBTS). In one there was also a native major
      aortopulmonary collateral artery (MAPCA). Another patient had a native major
      aortopulmonary connection (APC). Transcatheter occlusion was attempted in all
      cases through a 4 F delivery catheter. RESULTS: Devices were successfully
      deployed in 49/57 (86%) patients. Seven of 51 cases with persistent arterial
      ducts were judged too large for the device and a Rashkind umbrella was used. 40
      (91%) of the 44 in whom the detachable coil device was used had complete
      occlusion at 24 hours on colour flow Doppler echocardiography. Devices were
      successfully deployed in all 6 remaining patients (4 mBTS, 1 mBTS + MAPCA, and 1
      APC). Embolisation of a device occurred on 4 occasions. Two devices were not
      retrieved but caused no apparent clinical problems. CONCLUSION: This novel
      detachable coil type occlusion system compares favourably with other methods of
      transcatheter occlusion of native, residual, or surgically created aortopulmonary
      shunts. The delivery system allows its use in small children.

PMID- 9014801
TI  - Effects of blockade of fast and slow inward current channels on ventricular
      fibrillation in the pig heart.
AB  - OBJECTIVE: To determine the contribution of fast and slow inward channels to the
      electrocardiogram (ECG) of ventricular fibrillation. METHODS: Ventricular
      fibrillation was induced by endocardial electrical stimulation in pigs
      anaesthetised with pentobarbitone sodium (30 mg/kg intravenously). ECGs
      simultaneously recorded from the body surface (lead II) and from the endocardium
      were studied by power spectrum analysis (0-40 Hz). RESULTS: The mean (SEM)
      dominant frequency of fibrillation (9.0 (1.1) Hz in lead II at 0-40 s) did not
      change significantly with time in pigs given intravenous saline. However, the
      dominant frequency was significantly reduced by intravenous pretreatment with the
      class I antiarrhythmic drugs, lignocaine (3 mg/kg, 6.5 (0.5) Hz; 10 mg/kg, 4.2
      (0.6) Hz), mexiletine (3 mg/kg, 6.2 (0.4) Hz; 10 mg/kg, 5.5 (0.4) Hz), and
      disopyramide (2.5 mg/kg, 5.4 (0.6) Hz). After flecainide (3 mg/kg, 6.9 (0.5) Hz)
      the reduction in frequency was not significant. Similar data were obtained with
      endocardial recordings. In contrast pre-treatment with verapamil (0.2 mg/kg, 11.7
      (0.8) Hz; and 1.0 mg/kg, 12.9 (1.6) Hz) produced a significantly higher dominant
      frequency of fibrillation than saline and widened the bandwidth of frequencies
      around the dominant frequency. CONCLUSIONS: These results indicate that voltage
      dependent sodium channel currents contribute to the rapid frequencies of
      ventricular fibrillation. Blockade of L-type inward calcium channel activity
      increases the fibrillation frequency and fractionates the frequencies of the
      fibrillation wavefronts.

PMID- 9014803
TI  - Evolving use of embolisation coils for occlusion of the arterial duct.
AB  - OBJECTIVE: To assess the outcome of arterial duct occlusion with coils chosen
      according to the duct morphology. DESIGN: Retrospective study. SETTING:
      Paediatric cardiology centre. PATIENTS: Coil occlusion was attempted in 57
      patients aged 0.5 to 15 (median 3.7) years and weighing 5-59 (median 14) kg
      between January 1991 and December 1995. A residual leak was present in 8 patients
      after umbrella closure and in 4 patients after duct ligation. METHODS: Coils of 4
      different types were implanted through 4 or 5 F femoral artery catheters.
      Platinum or Interlocking Detachable 0.018 inch coils were deployed completely
      inside tubular ducts. Gianturco or PDA controlled release 0.038 inch coils were
      implanted to straddle short, post ligation and post umbrella ducts. RESULTS: Coil
      implantation was successful in 54/57 patients. At 1 year the cumulative occlusion
      rate was 53/57 ducts (93%) on an intention to treat analysis. A single coil was
      implanted in 37 (69%), 2 coils in 10 (19%), 3 coils in 3 (5%) and 4 coils in 4
      (7%) of the 54 successful procedures. Duct occlusion was documented at the end of
      the procedure in 31%, by the following day in 83%, by 6 weeks in 87%, by 6 months
      in 96%, and by 1 year in 98%. Coil embolisation occurred in 6/58 procedures
      (10%), with a 50% rate in the first year of implantation (1/2 patients) falling
      to 7% in the last year (3/42 patients). All embolised coils were easily
      retrieved. CONCLUSIONS: Occlusion of small to moderate size arterial ducts,
      including residual post umbrella or post ligation ducts, was readily accomplished
      by coils selected according to the duct anatomy. This has both cost and practical
      benefits.

PMID- 9014804
TI  - Transcatheter occlusion of the patent ductus arteriosus with Cook detachable
      coils.
AB  - OBJECTIVE: To report initial experience with a new occlusion device for native
      and residual patent ductus arteriosus. DESIGN: Descriptive study of consecutive
      non-randomised patients undergoing a new method of patent ductus arteriosus
      closure with detachable coils. SETTING: Tertiary centres for paediatric
      cardiology. PATIENTS: 71 consecutive patients, aged 1.2-22 years, with a patent
      ductus arteriosus (PDA) underwent elective transcatheter closure. 45 had native
      PDAs (group A) with a minimum diameter of 1.0 mm-5.0 mm (median 2.0 mm). A
      further 26 had undergone one or more previous occlusion attempts (group B).
      INTERVENTIONS: A total of 133 detachable (Cook) spring coils were successfully
      implanted in 70 patients. The procedure was performed transvenously in 51
      patients, retrograde arterially in 13, and by both routes in a further 6
      patients. One 5 mm coil migrated but was successfully retrieved. MAIN OUTCOME
      MEASURES: In group A colour flow Doppler echocardiography showed that complete
      occlusion was achieved in 40/45 (89%) at 24 hours, 41/45 (91%) at 1 month, and
      44/45 (98%) by 6 months post procedure. Occlusion rates in residual PDAs were
      22/25 (88%) occluded at 24 hours, 23/25 (92%) at 1 month, and 24/25 (96%) at 6
      months follow up. CONCLUSIONS: Transcatheter occlusion using detachable (Cook)
      spring coils is a safe and effective alternative to presently available devices.
      The delivery system allows full retrieval of the coil until a satisfactory
      position is obtained.

PMID- 9014805
TI  - Transcatheter closure of large patent ductus arteriosus (> or = 4 mm) with
      multiple Gianturco coils: immediate and mid-term results.
AB  - OBJECTIVE: To assess the immediate and mid-term results of transcatheter closure
      of patent ductus arteriosus (PDA) > or = 4 mm with multiple Gianturco coils.
      (Transcatheter closure of large PDAs using the Rashkind occluder or the buttoned
      device is associated with a 7-38% incidence of residual shunt.) METHODS: 19
      patients (7 male, 12 female) underwent an attempt at anterograde transcatheter
      closure with multiple Gianturco coils of a large PDA at a median age of 3.8 yr
      (range 2 weeks-34 yr) and median weight of 14 kg (range 2.3-80 kg). RESULTS: The
      median PDA diameter at the narrowest segment was 4.3 mm (range 4-7 mm) and the
      mean (SD) Qp/Qs was 1.9 (0.8). Each patient had left atrial and left ventricular
      volume overload. A 4F catheter was used to deliver the coils in all patients.
      There was immediate and complete closure in 16/18; one patient had residual shunt
      that was closed at a second procedure and the other had spontaneous disappearance
      of the residual shunt at the six week visit. A short ductus (angiographic type B)
      in one patient could not be closed. The median number of coils placed at the
      first attempt to close the ductus was 4 (range 2-6 coils) and the median
      fluoroscopy time was 40 minutes (range 13-152 minutes). Mild left pulmonary
      artery stenosis occurred in the two smallest patients. Coil migration to the lung
      occurred in 3 patients with retrieval of coils in two patients. All procedures
      but one were done on an outpatient basis. At a median follow up of 1.6 yr (range
      2 weeks-2.2 yr) all patients had complete closure with no new complications.
      CONCLUSIONS: Anterograde transcatheter closure with multiple Gianturco coils is
      an effective treatment for most patients with large PDA of diameters up to 7 mm.
      This technique can be performed in small infants on an outpatient basis without
      the need for general endotracheal anaesthesia.

PMID- 9014807
TI  - Isomerism of the atrial appendages associated with 22q11 deletion in a fetus.
AB  - There is a strong association between prenatally diagnosed structural heart
      disease and fetal chromosomal abnormalities. Isomerism of the atrial appendages
      is an exception to this because the fetal karyotype is usually normal in this
      condition. A case of atrial isomerism diagnosed antenatally with a normal female
      karyotype but with a microdeletion of chromosome 22q11 is reported.

PMID- 9014806
TI  - Wide complex tachycardia with atrioventricular dissociation and QRS morphology
      identical to that of sinus rhythm: a manifestation of bundle branch reentry.
AB  - OBJECTIVE: To determine the features that distinguish bundle branch reentry (BBR)
      ventricular tachycardia from a supraventricular tachycardia with aberration on
      the 12 lead electrocardiogram (ECG). PATIENTS: Three patients in whom premature
      beats (2 cases) or sustained tachycardia (2 cases) showed a QRS configuration
      identical to that observed during sinus rhythm. INTERVENTIONS: Programmed
      electrical stimulation. RESULTS: These arrhythmias were ventricular in origin and
      caused by a BBR mechanism, as suggested by the following data obtained during
      electrophysiological study: (a) an H-V interval shorter during tachycardia than
      during sinus rhythm; (b) A-V dissociation; (c) activation of the right bundle
      branch before activation of the bundle of His. The ECG of all 3 patients showed
      right bundle branch block with very prolonged QRS duration (0.16 to 0.20 s).
      Characteristically, all 3 had prolonged H-V interval during sinus rhythm. All
      patients had had a previous myocardial infarction and had a dilated left
      ventricle. CONCLUSION: The presence of (a) wide complex extrasystoles or
      tachycardia with a QRS morphology identical to that of sinus rhythm; (b) A-V
      dissociation; and (c) a very prolonged QRS duration (0.16 s or more) is
      suggestive of ventricular tachycardia caused by bundle branch reentry.

PMID- 9014808
TI  - Treatment of ventricular tachycardia-induced cardiomyopathy by transcatheter
      radiofrequency ablation.
AB  - Catheter ablation of ventricular tachycardia was successfully performed in a
      patient with dilated cardiomyopathy (ejection fraction 38%) and a long history of
      repetitive palpitations. Holter monitoring showed ventricular tachycardia that
      had a left bundle branch block QRS configuration with inferior axis deviation and
      was present for about one third of the daytime hours. At electrophysiological
      testing, ventricular tachycardia was reproduced by isoprenaline infusion.
      Radiofrequency energy delivered to the right ventricular outflow tract was
      successful at preventing the induction of ventricular tachycardia. Left
      ventricular ejection fraction had improved from 38% to 48% one month after
      ablation. During the follow up period of one year the patient remained free from
      arrhythmia on no medication. The ejection fraction was 61% one year after
      ablation. This report confirms that dilated cardiomyopathy can be induced by
      ventricular tachycardia and demonstrates that dilated cardiomyopathy can be
      reversed if the tachycardia is abolished by radiofrequency catheter ablation.

PMID- 9014809
TI  - Mucosal immunology: from bench to the bedside and beyond.
AB  - This paper, written by the President of the Society for Mucosal Immunology, marks
      the 9th International Congress of Mucosal Immunology, in Sydney: Mucosal
      Solutions. Current molecular, cellular and animal work in mucosal immunity has
      great potential when applied to issues of human and animal health. However,
      practical and technical problems in the transfer of theoretical concepts into
      clinically based research must not be underestimated. Ideally, studies in disease
      need to be designed and run jointly by clinicians and scientists, as illustrated
      by examples drawn from Crohn's disease. Ethical aspects of research in mucosal
      physiology and disease are challenging, but not insurmountable.

PMID- 9014810
TI  - The adjuvant effect of a non-toxic mutant of heat-labile enterotoxin of
      Escherichia coli for the induction of measles virus-specific CTL responses after
      intranasal co-immunization with a synthetic peptide.
AB  - The intranasal route has been shown to be effective for immunization. However,
      immunization via this route may require the use of potent and safe adjuvant. The
      construction of non-toxic mutants of heat labile enterotoxin of Escherichia coli
      (LT), which is a potent mucosal adjuvant, is a major breakthrough for the
      development of mucosal vaccines. In this study we have assessed the ability of an
      LT mutant (LTK63) to act as an adjuvant following intranasal co-immunization with
      a peptide corresponding to a measles virus cytotoxic T lymphocyte (CTL) epitope.
      LTK63 was more effective at potentiating the in vivo induction of peptide
      specific and measles virus-specific CTL responses than was administration of the
      peptide in saline. A concentration of 10 micrograms/dose of LTK63 was found to be
      the most effective in potentiating the in vivo priming of peptide-specific and
      measles virus-specific CTL responses. These findings highlight the potential of
      the non-toxic mutant of LT as a safe mucosal adjuvant for use in humans.

PMID- 9014811
TI  - Mucosal immunoadjuvant activity of liposomes: role of alveolar macrophages.
AB  - Previously, we have reported on a liposomal adjuvant system for stimulation of
      both systemic IgG and mucosal s-IgA responses against viral antigens (influenza
      virus subunit antigen or whole inactivated measles virus) administered
      intranasally to mice. Immune stimulation is observed with negatively charged, but
      not with zwitterionic, liposomes and is independent of a physical association of
      the antigen with the liposomes. Furthermore, liposome-mediated immune stimulation
      requires deposition of the liposomes and the antigen in the lower respiratory
      tract. In the present study, it is shown that alveolar macrophages (AM) are the
      main target cells for negatively charged liposomes administered to the lungs of
      mice. AM isolated from animals, to which negatively charged liposomes were
      administered beforehand, showed large intracellular vacuoles, suggestive of
      massive liposome uptake. Under ex vivo conditions, both AM and RAW 264 cells
      exhibited a high capacity to take up negatively charged liposomes. The deposition
      of negatively charged liposomes, but not zwitterionic, liposomes in the lung
      reduced the phagocytic and migratory behaviour of AM, as assessed on the basis of
      transport of carbon particles to the draining lymph nodes of the lungs. Depletion
      of AM in vivo with dichloromethylene diphosphonate, facilitated an enhanced
      systemic and local antibody response against influenza subunit antigen deposited
      subsequently to the lower respiratory tract. In conclusion, these data provide
      support for the hypothesis that uptake of negatively charged liposomes blocks the
      immunosuppressive activity of AM, thereby facilitating local and systemic
      antibody responses.

PMID- 9014812
TI  - Microbial colonization influences composition and T-cell receptor V beta
      repertoire of intraepithelial lymphocytes in rat intestine.
AB  - Studies in mice have shown that the composition of intestinal intraepithelial
      lymphocytes (IEL) may be markedly altered by gut microbial colonization. Such
      modulation was studied in a rat model by the use of germ-free and
      conventionalized animals from which IEL from the small intestine were isolated
      and analysed by flow cytometry. Conventionalization caused expansion as well as
      phenotypic alterations of T-cell receptor (TCR) alpha/beta + IEL in that the
      proportions of CD4+ and CD8 alpha beta + TCR alpha/beta + cells were increased,
      while the double negative (CD4- CD8-) fraction was reduced. microbial
      colonization also influenced the TCR V beta repertoire of CD8+ IEL in that the
      proportions of V beta 8.2+ and V beta 10+ cells were increased, whereas V beta
      8.5+ and V beta 16+ cells were relatively decreased. Moreover,
      conventionalization influenced the levels of TCR cell surface expression in the
      same V beta subsets. Three-colour flow-cytometric analysis demonstrated that
      skewing of the V beta repertoire was most pronounced in the CD8 alpha alpha +
      subset, although the numerical increase of IEL mainly included the CD8 alpha beta
      + subset. In contrast to IEL, the TCR V beta repertoire in mesenteric lymph nodes
      was unchanged after intestinal colonization. These results confirm that TCR
      alpha/beta + IEL subpopulations respond dynamically to the microbial gut flora
      and suggest that their V beta repertoire can be shaped by luminal microbial
      antigens.

PMID- 9014813
TI  - Contribution of CD4+ and CD8+ T lymphocyte subsets to the cytokine secretion
      patterns induced in mice during sensitization to contact and respiratory chemical
      allergens.
AB  - Chemical allergens of different types, those that cause in humans allergic
      contact dermatitis or occupational asthma induce in mice divergent immune
      responses characteristic, respectively, of T-helper 1 (Th1)- and Th2-type cell
      activation. Such responses are associated with the development of different
      cytokine secretion patterns by draining lymph node cells (LNC), such that contact
      allergens stimulate vigorous interferon-gamma (IFN-gamma) production, but little
      secretion of the Th2 cytokines interleukin-4 and interleukin-10 (IL-4 and IL-10),
      whereas the converse pattern is provoked by respiratory allergens. Using
      selective depletion with antibody and complement we have here examined the
      relative contribution of CD4+ and CD8+ T lymphocytes to the cytokine secretion
      patterns of draining LNC isolated from mice sensitized to chemical allergens.
      Mice received repeated topical applications of respiratory allergens, trimellitic
      anhydride (TMA) or diphenylmethane diisocyanate (MDI), or of contact allergens
      2,4-dinitrochlorobenzene (DNCB) or formaldehyde. Thirteen days following the
      initiation of exposure the production by draining LNC of IL-10, IFN-gamma and
      mitogen (concanavalin A)-inducible IL-4 was measured by enzyme-linked
      immunosorbent assay (ELISA) after various periods of culture. It was found that
      the high levels of IL-4 and IL-10 secretion stimulated by TMA or MDI, and the
      lower levels of these cytokines induced by DNCB or formaldehyde, were in all
      cases dependent upon the presence of CD4- cells. In contrast, the comparatively
      high concentrations of IFN-gamma observed following exposure to contact allergens
      were found to be derived from CD4+ cells, and in the case of DNCB from CD8+ cells
      also. The low levels of IFN-gamma induced by treatment with TMA or MDI were
      associated largely or wholly with CD8+ cells. These data indicate that the type 2
      cytokine responses induced to different extents by both contact and respiratory
      chemical allergens are almost exclusively a function of CD4+ cells, but that IFN
      gamma is produced by either CD4+ cells in the case of contact allergens or
      largely by CD8+ cells in the case of chemical respiratory allergens.

PMID- 9014814
TI  - Release of preformed Fas ligand in soluble form is the major factor for
      activation-induced death of Jurkat T cells.
AB  - Interaction of Fas/APO-1 (CD95) and its ligand (FasL) plays an important role in
      the activation-induced cell death (AICD) of T lymphocytes. In the present work,
      the contribution of soluble FasL to AICD of the human T-cell line Jurkat has been
      studied. Jurkat cells prestimulated with phytohaemagglutinin (PHA) induced the
      death of non-activated Jurkat cells, and also of L1210Fas, but not that of Fas
      negative L1210 cells. Culture supernatants from prestimulated Jurkat cells were
      highly toxic to their non-activated counterparts. Time-course analysis revealed
      that PHA-stimulated Jurkat cells quickly release (less than 15 min) to the medium
      a toxic molecule following a biphasic pattern, with maximal cytotoxic activities
      at 1 hr and 7 hr after stimulation. The cytotoxic effect of those supernatants
      was prevented by the addition of a blocking anti-Fas monoclonal antibody,
      suggesting that PHA-stimulated Jurkat cells exert Fas-based cytotoxicity mainly
      through the release of soluble FasL. The constitutive intracellular expression of
      FasL in non-activated Jurkat cells and its release as a consequence of PHA
      activation were detected by immunostaining and immunoblotting using an anti-FasL
      antibody. These data indicate that, at least in Jurkat cells, AICD is mainly
      mediated by the rapid release of performed FasL in soluble form upon stimulation.

PMID- 9014815
TI  - A new immunosuppressant, FTY720, induces bcl-2-associated apoptotic cell death in
      human lymphocytes.
AB  - FTY720 is a unique immunosuppressive drug produced by modification of a
      metabolite from Isaria sinclairii. In vitro treatment of human mononuclear cells
      with FTY720 resulted in a dose-dependent reduction of cell viability. These
      treated cells demonstrated characteristic DNA ladder formation on agarose gel
      electrophoresis. Jurkat cells transfected with human bcl-2 gene were resistant to
      FTY720; their neo type was susceptible to the drug. A rapid acceleration of cell
      death in human mononuclear cells was seen as early as 2 hr after incubation with
      FTY720. The intracellular Bax protein increased remarkably 1 hr after the
      culture; it markedly decreased in the surviving cells at 2 and 3 hr. Coincidental
      to the Bax decrease. Bcl-2 progressively decreased beginning 2 hr after the
      culture. Thus, the ratio of Bcl-2 to Bax was decreased by the enhanced expression
      of Bax immediately after FTY720-treatment, resulting in rapid cell death
      acceleration. The surviving cells (FTY720-resistant cells) at 2 and 3 hr after
      culture showed a similar ratio of Bcl-2 to Bax as was observed in the control
      cells. These results suggest that FTY720 displays bcl-2-associated apoptotic cell
      death in human mononuclear cells.

PMID- 9014816
TI  - Cyclosporin A abrogates the acquired immunity to cutaneous reinfection with the
      parapoxvirus orf virus.
AB  - The effect of cyclosporin A (CsA) on host immunity to cutaneous reinfection with
      the parapoxvirus orf virus was studied in 6-month-old lambs. In control
      reinfected animals, clinical lesions and viral replication (measured by the
      presence of vesicular/pustular lesions and viral antigen) in regenerating
      epidermal cells were at a maximum on day 4 with resolution by day 9. Lesion
      histology revealed recruitment of T cells, B cells and dermal dendritic cells
      (DDC) which increased and decreased in parallel with the clinical course of the
      reinfection. In animals treated with CsA (25 mg/kg/day) 1 day before and for 8
      days after reinfection, more severe clinical lesions and viral replication
      typical of primary infections were recorded and had not resolved by 28 days
      following reinfection. During CsA treatment, the recruitment of T cells, B cells
      and DDC was inhibited. With cessation of CsA treatment there was dramatic
      recruitment of CD4+ T cells followed by DDC then B cells to the lesion site but
      rapid onset of acquired immunity was not recorded. Reverse transcription
      polymerase chain reaction (RT-PCR) analysis of cytokine mRNAs from lesion
      biopsies showed individual sheep variations. However, interleukin-2 (IL-2) and
      interferon-gamma (IFN-gamma) mRNAs were detected in the control reinfected
      animals on days 3 and/or 9 after reinfection but not on these days in animals
      undergoing treatment with CsA. In the untreated lambs there was an inexplicable
      lack of IL-2 and IFN-gamma mRNAs on day 6 after reinfection. Tumour necrosis
      factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) mRNAs were
      unaffected by CsA treatment. The data suggest that CsA abrogates acquired
      immunity to orf virus reinfection by targetting T-cell lymphokine production.

PMID- 9014818
TI  - Inflammation-induced changes in the phenotype and cytokine profile of cells
      migrating through skin and afferent lymph.
AB  - In the present study, we have localized cytokine-secreting cells within an
      ectoparasite-induced inflammatory lesion and monitored the phenotype and cytokine
      profile of cells migrating from the inflammatory lesion to the local draining
      lymph node via the afferent lymphatics. Interleukin (IL)-8-producing cells were
      first detected in skin within 6 hr of infection, with increased numbers observed
      at 24 and 48 hr post infection. While these cells were concentrated within the
      neutrophil influx, adjacent to disrupted epidermis; they were also found
      scattered throughout the surrounding dermis in areas where significant cellular
      infiltration was not apparent. IL-1 alpha- and IL-1 beta-producing cells could
      not be detected until 24 hr after infection and were restricted to areas of
      intense neutrophil accumulation. Concurrent with the onset of inflammation was a
      threefold increase in the total number of cells migrating through the draining
      afferent lymph. This increase in cellularity was due primarily to increased
      migration of CD4 and gamma delta T cells. Cytokine mRNA synthesis by migrating
      afferent lymph cells was examined by reverse transcription-polymerase chain
      reaction (RT-PCR) analysis of RNA extracted prior to, and at regular intervals
      during the course of the inflammatory response. IL-1 beta and IL-8, but not IL-1
      alpha or IL-6 mRNA, was detected in migrating afferent lymph cells. Tumour
      necrosis factor (TNF)-alpha-specific mRNA was present in migrating afferent lymph
      cells at all time points both prior to, and following infection. Soluble IL-8
      protein, but not IL-1 alpha, IL-1 beta or TNF-alpha protein, could be detected in
      lymph, with the amount of IL-8 detected increasing as the infection progressed.
      mRNA coding for cytokines associated with T-cell activation, such as IL-2, IL-4
      or interferon (IFN)-gamma, was also detected in migrating cells, although the
      cytokine profiles of different experimental animals were extremely variable.

PMID- 9014817
TI  - Th0-like CD4+ T cells protect mice with murine retrovirus-induced
      immunodeficiency syndrome (MAIDS) against co-infection with Listeria
      monocytogenes.
AB  - We examined the host defence mechanism against infection with Listeria
      monocytogenes, a facultative intracellular bacterium, in mice with murine
      acquired immunodeficiency syndrome (MAIDS) caused by LP-BM5 murine leukaemia
      virus (MuLv) infection. Although LP-BM5 MuLV infection in C57BL/6 mice leads to a
      stage of immunodeficiency characterized by severe compromise of cell-mediated
      immunity, the mice with established MAIDS infected with LP-BM5 8 weeks
      previously, showed resistance to an intraperitoneal infection with Listeria
      monocytogenes. These MAIDS mice also showed resistance to a lethal dose of
      secondary listerial challenge, while the delayed-type hypersensitivity response
      to heat-killed Listeria (HKL.) was severely impaired in MAIDS mice. The
      resistance of MAIDS mice to listerial infection was mediated by CD4+ alpha beta T
      cells but neither by gamma delta T cells nor natural killer (NK) cells.
      Interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) were produced by CD4+ T
      cells from Listeria-infected MAIDS mice in response to the in vitro stimulation
      with HKL, whereas IFN-gamma but not IL-10 were produced by those from Listeria
      infected control mice. These results suggest that T-helper 0 (Th0)-like immune
      responses of CD4+ T cells occur and participate in host defence mechanisms
      against listerial infection in MAIDS mice.

PMID- 9014819
TI  - Interferon-gamma promotes the survival and Fc epsilon RI-mediated histamine
      release in cultured human mast cells.
AB  - We examined the effects of interferon-gamma (IFN-gamma) on 100% pure human mast
      cells generated in suspension cultures of umbilical cord blood mononuclear cells
      in the presence of stem cell factor (SCF) and interleukin-6 (IL-6). When mast
      cells were suspended in serum-free medium without any cytokine after the
      withdrawal of SCF and IL-6, they died over a period of 5 days because of
      apoptosis. IFN-gamma in the cultures suppressed apoptosis and prolonged their
      survival in a dose-dependent manner. This survival-promoting effect of IFN-gamma
      was blocked by neutralizing antibodies to IFN-gamma or to IFN-gamma receptor (IFN
      gamma R). When mast cells were incubated with IFN-gamma in serum-free medium for
      more than 4 hr during sensitization, immunoglobulin E (IgE)/anti-IgE antibody
      induced histamine release was effectively enhanced. Polymerase chain reaction
      (PCR) amplification of the alpha-chain of IFN-gamma R (IFN-gamma R alpha) yielded
      products of the correct size predicted from the sequence of the receptor. In
      addition, flow cytometry using anti-IFN-gamma R monoclonal antibodies (mAbs)
      indicated that these mast cells bear IFN-gamma R on their surface. These findings
      suggested that IFN-gamma activates human mast cells via specific receptors in
      certain aspects of inflammatory reactions.

PMID- 9014820
TI  - TNF-alpha-mediated expression of membrane-type matrix metalloproteinase in
      rheumatoid synovial fibroblasts.
AB  - Degradation of the extracellular matrix plays an important role in rheumatoid
      articular destruction. Rheumatoid synovial fibroblasts secrete a large amount of
      matrix-degrading metalloproteinases (MMPs), which initiate tissue damage by
      proteolytic degradation of collagens and proteoglycans. Cytokines, such as
      interleukin-1 alpha, -1 beta or tumour necrosis factor (TNF)-alpha, are potent
      inducers of MMPs in rheumatoid synovial fibroblasts, MMPs are synthesized and
      secreted as latent pro-enzymes and their activation is achieved by proteolytic
      cleavage or the propeptide domain at the N-terminus of the molecule. Thus, the
      interaction of the pro-enzymes with specific activators determines the enzymatic
      activity in the extracellular space. In the present study, we identified a novel
      mechanism for the activation of pro-MMP-2, which can be achieved through the
      interaction of the inflammatory cytokine, TNF-alpha, with synovial fibroblasts.
      Although MMP-2 is constitutively secreted by synovial fibroblasts as a pro
      enzyme, stimulation of fibroblasts by TNF-alpha-induced secretion of MMP-2 in an
      active form. In support of this result, TNF-alpha stimulation-induced membrane
      type matrix metalloproteinase (MT-MMP), a newly identified MMP-2-specific
      activator on synovial fibroblasts. Cycloheximide analysis demonstrated that
      protein synthesis may be required for TNF-alpha-mediated MT-MMP expression on
      synovial fibroblasts. Our results suggest that TNF-alpha induces MMP-2 activation
      in part by up-regulating MT-MMP expression, thus representing a new mechanism for
      cytokine-mediated articular destruction in rheumatoid arthritis (RA).

PMID- 9014822
TI  - Cytokine production of neutrophils is limited to interleukin-8.
AB  - Since granulocytes are one of the first cell types at sites of inflammation,
      investigation of their capacity to produce cytokines has concentrated on
      interleukin-1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor-alpha (TNF
      alpha). However, the results are subject to controversy. Incapability to produce
      cytokines as well as a broad panel of cytokines induced by isolation procedures
      are reported. The purpose of this study was to investigate the capacity of non
      prestimulated neutrophils to produce the above-mentioned cytokines in response to
      stimulation with lipopolysaccharide or zymosan. In reverse transcription
      polymerase chain reactions, we found IL-8 mRNA directly after isolation in
      unstimulated cells, whereas mRNA for IL-1 beta, IL-6 and TNF-alpha only appeared
      after stimulation. By means of flow cytometry we ruled out the possibility of
      prestimulation of the neutrophils during isolation, proving that IL-8 mRNA is
      produced constitutively by neutrophils. In enzyme-linked immunosorbent assays we
      found that, compared with controls, only IL-8 was released at significantly
      higher levels after 24 hr of stimulation, giving a further indication that
      neutrophils have an immunoregulatory influence driven by IL-8. We can confirm
      neither a constitutive nor a post-stimulatory release of IL-1 beta, IL-6, or TNF
      alpha by neutrophils, as had been reported by others. These observations may be
      due to prestimulation, handling and culturing of the granulocytes, or to monocyte
      contamination. Collectively, our results show that granulocytes have a preformed
      capacity to produce the cytokine IL-8 and that the production of proinflammatory
      cytokines by neutrophils is limited to IL-8.

PMID- 9014821
TI  - 3-Deazaadenosine analogues inhibit the production of tumour necrosis factor-alpha
      in RAW264.7 cells stimulated with lipopolysaccharide.
AB  - The effects of 3-deazaadenosine (DZA), 3-deaza(+/-)-aristeromycin (DZAri) and 3
      deazaneplanocin (DZNep) on tumour necrosis factor-alpha (TNF-alpha) production
      were examined in the mouse macrophage cell line, RAW264.7, stimulated with
      lipopolysaccharide (LPS). The 3-deazaadenosine analogues inhibited the TNF-alpha
      production and the inhibition was dependent upon the concentration of the
      analogue. DZA reduced the level of TNF-alpha mRNA suggesting that DZA acts at a
      transcriptional step. In contrast, DZAri and DZNep had little effect on mRNA
      levels for TNF-alpha, implying that these compounds inhibit a post
      transcriptional or translational biosynthetic step of TNF-alpha synthesis. The
      observation that homocysteine (Hcy) potentiated the DZA inhibition of TNF-alpha
      production and of TNF-alpha mRNA levels suggests that the inhibition of TNF-alpha
      production may be caused by elevated levels of 3-deazaadenosylhomocysteine
      (DZAHcy). The results show that the 3-deazaadenosine analogues are potent
      inhibitors of TNF-alpha production in the RAW264.7 cell line stimulated with LPS
      and suggest that these analogues may be effective agents for the treatment of
      diseases in which TNF-alpha plays an important pathogenic role.

PMID- 9014823
TI  - The influence of IL-7 V(D)J recombination.
AB  - The influence of interleukin-7 (IL-7) on V(D)J recombination was investigated
      directly in the V(D)J recombination competent pre-B-cell line 38B9. The addition
      of IL-7 to the medium reduced the V(D)J recombination rate by 52-64%. This
      reduction was insensitive to the addition of cyclosporin A, indicating that the
      repression by IL-7 is not mediated by phosphatase 2B. The repression mechanism of
      IL-7 did not synergize with those of the protein kinase C activator 12-O
      Tetradecanoylphorbol-13-acetate (TPA) and the intracellular Ca2+ mobilizer
      thapsigargin. The actin of IL-7 blocked by the addition of the protein kinase A
      stimulator caffeine and the synthetic glucocorticoid dexamethasone. IL-7 did not
      change the m-RNA levels of the V(D)J recombination activating genes RAG-1 and RAG
      2, therefore IL-7 must exert its influence on V(D)J recombination either by post
      transcriptional regulation of the RAG genes or by the regulation of other genes
      that are involved in V(D)J recombination. Although IL-7 may be necessary for the
      induction of and maintenance of V(D)J recombination during some stages of
      lymphocyte precursor development, it reduces the V(D)J recombination activity in
      pre-B cells.

PMID- 9014824
TI  - Increased clearance of IgG in mice that lack beta 2-microglobulin: possible
      protective role of FcRn.
AB  - The mechanisms that regulate immunoglobulin G (IgG) catabolism are little
      understood. We have previously found unusually low IgG concentrations in sera of
      mice homozygous for a targeted disruption of the beta 2-microglobulin gene. We
      therefore investigated whether this might result, at least in part, from
      increased clearance of IgG from the systemic circulation in mice lacking beta 2
      microglobulin. We compared the half-lives of radiolabelled mouse IgG1 injected
      intravenously into beta 2-microglobulin-/- mice and wild-type or heterozygous
      siblings. The clearance of 125I-labelled IgG1 was strikingly more rapid in the
      mice lacking beta 2-microglobulin. beta 2-microglobulin-/- mice lack functional
      molecules of the MHC class I-related Fc receptor, FcRn. Some mutations in mouse
      IgG1 that increase its clearance have recently been shown to prevent binding to
      FcRn in the gut. To determine whether the slower degradation of immunoglobulin in
      mice with beta 2-microglobulin correlated with the ability of the antibody to
      bind FcRn, we measured the clearance of chicken IgY, which does not bind this
      receptor. The 125I-labelled IgY was catabolized equally rapidly in beta 2
      microglobulin-deficient and wild-type mice. We compared the half-lives of the
      four subclasses of mouse IgG in beta 2-microglobulin-/-, +/-, and +/+ mice to
      determine whether the difference we had noted for IgG1 was peculiar to this
      subclass. The 125I-labelled IgG of all subclasses, with the possible exception of
      IgG2b. was degraded more rapidly in the beta 2-microglobulin-deficient mice than
      in heterozygous or wild-type siblings. These data suggest that FcRn can protect
      IgG from degradation, and is therefore important in maintaining IgG levels in the
      circulation.

PMID- 9014826
TI  - Differential expression of function-related antigens on newborn and adult
      monocyte subpopulations.
AB  - Umbilical cord blood and adult peripheral blood monocytes were separated into two
      subpopulations, based on the intensity of CD14 expression, and the coexpression
      of various antigens associated with monocyte function was examined. The majority
      of cord and adult monocytes expressed CD14 at a high density (CD14bright) while
      approximately 15% of monocytes expressed this antigen at a lower level (CD14dim).
      Three times as many CD14dim monocytes expressed CD16 (Fc gamma RIII) as did
      CD14bright monocytes in both cord and adult preparations, while its level of
      expression (mean fluorescence intensity) was significantly reduced on cord
      CD14dim monocytes relative to adult CD14dim monocytes. The percentage of cord
      blood CD14dim monocytes expressing human leucocyte antigen-DR (major
      histocompatibility complex class II antigen) was significantly reduced relative
      to adult CD14dim cells; however, the level of expression of this antigen was
      greater on both cord and adult CD14dim monocytes compared with CD14bright cells.
      Cord CD14bright cells expressed CD36 (OKM5) to a greater extent than did their
      adult counterparts. The level of expression of CD62L was reduced on cord CD14dim
      cells compared with adult CD14dim cells. CD11b (CR3) was expressed both on a
      higher percentage of cells and also with a greater intensity on both cord and
      adult CD14bright monocytes compared with their CD14dim counterpart. These results
      show that significant differences exist between cord and adult monocyte
      subpopulations with regard to expression of various antigens associated with
      specific effector function.

PMID- 9014825
TI  - Peptides isolated from random peptide libraries on phage elicit a neutralizing
      anti-HIV-1 response: analysis of immunological mimicry.
AB  - Peptides binding to a murine, human immunodeficiency virus type 1 (HIV-1)
      neutralizing monoclonal antibody (F58/H3) were isolated from two random peptide
      libraries expressed on the surface of phage. The antibody was originally elicited
      by immunization with HIV-1 envelope protein gp120LAI, and has previously been
      shown to interact with the -I-GPGRA- motif of the V3 loop. The peptide libraries
      consisted of nine or 15 random amino acid residues flanked by two cysteines, and
      fused to the amino terminal end of the cpIII protein on the filamentous phage.
      Selection of specific peptides was carried out in three rounds, with decreasing
      antibody concentration. An expected peptide motif -GPGRA-, a similar segment, 
      GPAR-, and two unrelated motifs -FRLLG- and -WRM/ALG- were selected. Binding of
      antibody was tested both to synthetic peptides in solution, and the corresponding
      peptide on phage. The GPXR motifs bound in both formats, while the FRLLG bound
      antibody only when present on the phage The reactivity of peptides on phage was
      highly dependent on an intact disulphide bond between the cysteines flanking the
      peptide. The molecular mimicry of the found motifs was tested by immunizing mice
      and rabbits with conjugated synthetic peptides or peptide on phage. In mice,
      peptide-specific antisera were raised, but no reactivity to the whole protein
      (gp120) was detected. In rabbits, however, this was accomplished with the -GPGRA-
      containing peptide when present on phage. In addition, this antisera precipitated
      virus particles, and neutralized HIV-1SF2 virus in vitro.

PMID- 9014828
TI  - Control of major histocompatibility complex class II expression on human
      monocytes by interleukin-4: regulatory effect of lipopolysaccharide.
AB  - Interleukin-4 (IL-4), like interferon-gamma (IFN-gamma), stimulates monocyte
      major histocompatibility complex (MHC) class II expression and thus, by
      increasing antigen presentation, has the potential to increase immune reactivity.
      In this study, activation of human monocytes by lipopolysaccharide (LPS)
      prevented concomitant IL-4 stimulation of MHC class II expression. However, this
      was not a general observation for activated monocytes because although the high
      levels of MHC class II antigen expressed by monocytes stimulated in vitro with
      IFN-gamma were not further regulated by IL-4, the stimulatory effects of IL-4
      persisted on cells activated with granulocyte macrophage colony-stimulating
      factor and tumour necrosis factor-alpha for enhanced MHC class II expression. MHC
      class II expression by monocytes cultured for 7 days with macrophage colony
      stimulating factor was regulated by IL-4 and LPS in a manner very similar to that
      detected for freshly isolated monocytes. The inhibitory effect of LPS was not due
      to LPS-induced production of IL-10 or regulatory prostanoids. Furthermore, IFN
      gamma-increased MHC class II expression was suppressed by LPS, suggesting that
      the regulation was at the level of MHC class II expression per se. This study
      suggests that during Gram-negative bacterial infections, IL-4 and IFN-gamma may
      not be able to signal enhanced MHC class II expression and thus, enhanced immune
      reactivity.

PMID- 9014827
TI  - Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human
      peripheral blood monocytes.
AB  - The interaction of CD28 with its ligands is important for T-cell activation.
      Recent studies demonstrated the existence of at least two ligands on accessory
      cells, CD80 (B7-1) and CD86 (B7-2). In this study we demonstrate that, although
      CD80 and CD86 are both expressed on monocytes, they seem to have different
      functions. Freshly isolated monocytes express CD86 but are CD80-negative. CD80
      expression is weakly induced after 6-8 hr of in vitro culture and is enhanced by
      stimulation. CD86 expression is enhanced faster than CD80 expression and reaches
      the peak level after 4-6 hr in stimulated cells. Reverse transcription-polymerase
      chain reaction studies demonstrate that freshly isolated monocytes contain no
      CD80-mRNA. The mRNA of CD80 is induced after 4-6 hr of culture, which matches
      with the expression of the protein. Inhibition studies using different antibodies
      against both molecules and the fusion protein CTLA4Ig show that only anti-CD80
      and CTLA4Ig could partially inhibit antigen-specific (tuberculin) and polyclonal
      (anti-CD3) lymphoproliferation and interferon-gamma (IFN-gamma) secretion of T
      cells cocultured with autologous monocytes. IFN-gamma secretion was more
      sensitive to blocking costimulation than proliferation. The antibody BB-1 did not
      inhibit proliferation and cytokine secretion, nor did the anti-CD86 clone IT2.2.
      CTLA4Ig, which binds both CD80 and CD86, has the same inhibitory capacity as the
      anti-CD80 antibody tested. From those findings we conclude that human monocytes
      use CD80 as a costimulatory ligand for CD28 and utilize other costimulatory
      mechanisms besides those mediated via molecules of the B7 family.

PMID- 9014830
TI  - Lipids from Mycobacterium leprae cell wall are endowed with an anti-inflammatory
      property and inhibit macrophage function in vivo.
AB  - In general, the majority of bacteria are pre-inflammatory when injected in
      experimental animals. However, Mycobacterium leprae has no inflammatory effect
      when injected into mouse footpad, but using the delipidated mycobacteria we
      observed a mild significant increase in footpad oedema. Other mycobacteria,
      Mycobacterium bovis-BCG or M. tuberculosis induce a strong paw oedema.
      Furthermore, M. leprae reduced locally the BCG-induced inflammatory reaction in
      mouse footpad, whereas delipidated M. leprae did not influence this reaction.
      Both M. leprae and M. leprae cell wall lipids blocked immune phagocytosis in vivo
      by inflammatory macrophages (from an induced focus). In contrast delipidated M.
      leprae stimulated the phagocytosis reaction. Neither intact M. leprae.
      delipidated M. leprae, nor its lipids had any toxic effect on macrophages or on
      cell migration. Although M. leprae did not interfere on cell influx and cell type
      in an induced-inflammatory site, this mycobacterium led to the appearance of a
      distinct cell population in vivo. The hypothesis is that M. leprae would
      transform macrophages in epithelioid cells, suggested by morphology analysis of
      cells by fluorescence-activated cell sorter and observed under optic microscopy.

PMID- 9014829
TI  - MUTZ-3, a monocytic model cell line for interleukin-4 and lipopolysaccharide
      studies.
AB  - The human monocytic cell lines MUTZ-3 and MONO-MAC-6 express the
      lipopolysaccharide (LPS) receptor CD14. Paralleling the situation in peripheral
      blood monocytes (PBMo), recombinant human interleukin-4 (IL-4) down-regulated the
      expression of CD14 on the cell surface of MUTZ-3, but not that of MONO-MAC-6
      cells. In addition, preincubation with IL-4 prevented the LPS-induced up
      regulation of IL-1 beta mRNA levels in MUTZ-3, but not in MONO-MAC-6 cells. We
      examined whether the differential responsiveness of the cell lines was due to the
      missing expression of the IL-4 receptor (IL-4R) alpha or gamma c chain in MONO
      MAC-6 cells. Flow cytometric and immunoprecipitation analysis revealed expression
      of both IL-4R chains in both cell lines. In addition, short-term stimulation with
      IL-4 induced tyrosine-phosphorylation of the gamma c chain. As both cell lines
      also expressed signal transducer and activator of transcription 6 (STAT 6), our
      data suggested that the differential reaction patterns of MUTZ-3 and MONO-MAC-6
      cells were not due to a generally defective IL-4R complex. Interestingly, long
      term (48 hr) treatment with LPS rendered MONO-MAC-6 cells sensitive to IL-4. LPS
      up-regulated expression of monocyte-specific esterase (MSE) mRNA as well as CD14
      protein in MONO-MAC-6 cells; both effects were inhibited by IL-4. This
      stimulation was not paralleled by an increase of IL-4R mRNA or protein expression
      supporting the above hypothesis of a constitutively present and active IL-4R. We
      discuss possible causes for the differential reaction patterns of MUTZ-3 and MONO
      MAC-6 cells to IL-4.

PMID- 9014831
TI  - Role of prolactin in the in vitro development of interleukin-2-driven anti
      tumoural lymphokine-activated killer cells.
AB  - Exogenous prolactin (PRL) has been shown to synergize with low-dose interleukin-2
      (IL-2) and induce the proliferation and lymphokine-activated killer (LAK)
      maturation of natural killer (NK) cells. PRL itself can also generate LAK
      activity. Here we show that its local production occurs during, and is necessary
      for, LAK development. IL-2-stimulated peripheral blood mononuclear cells (PBMC)
      and purified NK cells were exposed to anti-human (h)PRL antiserum, and residual
      LAK activity was measured on day 7 against the promyelocytic leukaemia cell line
      HL-60. Inhibition of LAK activity was much more evident in PBMC compared with NK
      cell cultures (47% decrease. P - 0.013 and 18.5% decrease. P = 0.048,
      respectively). Up-modulation of a 32S-methionine-labelled 27,000 MW protein was
      detected in the lysates and supernatants of IL-2-stimulated PBMC
      immunoprecipitated with an anti-PRL antiserum. By contrast, the cytoplasmic PRL
      immunoreactivity observed in freshly isolated NK cells and in IL-2-stimulated,
      but not unstimulated, NK cell cultures was not associated with PRL gene
      activation, and can thus be referred to internalized PRL. Preferential re-uptake
      of externally derived PRL by IL-2-stimulated NK cells was also indicated by up
      modulation of the PRL receptor. These data, as a whole, indicate that the PRL
      promotion of LAK differentiation is mainly mediated by paracrine secretion, with
      a minor contribution from internalized PRL.

PMID- 9014833
TI  - Cardiovascular effects of GH.

PMID- 9014832
TI  - The emergence of non-cytolytic NK1.1+ T cells in the long-term culture of murine
      tumour-infiltrating lymphocytes: a possible role of transforming growth factor
      beta.
AB  - The mechanism by which murine tumour-infiltrating lymphocytes (TIL) decreased
      their anti-tumour activity during an in vitro culture with interleukin-2 (IL-2)
      was investigated. A phenotype analysis revealed that the TIL cultured for 7 days
      (TIL-d7) were exclusively NKI.1- CD4- CD8+ CD3+ cells and that this population
      was replaced by natural killer (NK)1.1+ CD4- CD8 CD3+ cells by day 27 (TIL-d27)
      during the culture of TIL. The TIL-d7 cells showed a cytolytic activity against
      B16 melanoma, whereas the TIL-d27 cells had lost this activity, suggesting that
      the decrease in the anti tumour effect of TIL during the culture with IL-2 was
      due to their populational change. Analysis on the characteristics of the TIL-d27
      cells revealed that they expressed skewed T-cell receptor (TCR) V beta 5 and
      increased mRNA expression of V alpha 14. In addition, they expressed transforming
      growth factor beta (TGF-beta) mRNA. Interestingly, TGF-beta augmented the
      proliferation of TIL-d27 cells under the presence of IL-2, but suppressed that of
      TIL-d7 cells. Moreover, the proliferation of TIL-d27 cells was suppressed by anti
      TGF-beta monoclonal antibody. Collectively, these results suggest that, in
      contrast to its suppressive effect on anti-tumour effector T cells. TGF-beta
      could be an autocrine growth factor for NKL1.1+ T cells and thereby induce non
      cytolytic NK1.1+ T cells in the long-term culture of TIL.

PMID- 9014834
TI  - Angiotensin II is generated from angiotensin I by bone cells and stimulates
      osteoclastic bone resorption in vitro.
AB  - During bone resorption, osteoclasts are closely associated with endothelial
      cells. The latter are able to produce several agents that regulate bone
      resorption. In view of the increasing evidence that angiotensin II, which can be
      generated by endothelial cells, has actions outside the traditional renin
      angiotensin system, we tested the effect of angiotensin II on bone resorption
      Angiotensin II showed no effect either on osteoclast formation or on bone
      resorption by isolated osteoclasts. However, in co-cultures of osteoclasts with
      calvarial or MC3T3-E1 osteoblastic cells, and in osteoclastic cultures co
      cultured with other bone cells obtained by prolonged sedimentation, angiotensin
      II stimulated bone resorption to a similar degree to that observed with 1,25(OH)2
      vitamin D3. Stimulation of resorption was noted at concentrations of 10(-7) M and
      above. We found that angiotensin I also stimulated bone resorption in co-cultures
      of osteoclasts with osteoblastic cells, and that this action was inhibited by
      inhibitors of angiotensin-converting enzyme. These results identify angiotensin I
      and II as potent stimulators of osteoclastic bone resorption, and raise the
      possibility that bone might contain a tissue-renin-angiotensin system that might
      play a role in the regulation of bone resorption.

PMID- 9014835
TI  - Localisation of mRNA for interleukin-1 receptor and interleukin-1 receptor
      antagonist in the rat ovary.
AB  - Interleukin-1 (IL-1) is a multifunctional cytokine with profound effects on
      ovarian function. The effects of IL-1 on ovarian steroidogenesis have been
      demonstrated in several species. IL-1 mRNA levels are increased in the thecal
      layer of the ovulating follicle and IL-1 beta has been shown to induce ovulations
      in vitro. In this study we have investigated the presence and distribution of the
      mRNAs for type I IL-1 receptor (IL-1RtI) and for the naturally occurring IL-1
      receptor antagonist (IL-1ra) in ovaries of adult cycling rats, to elucidate the
      target cells for IL-1 action. We have demonstrated the presence of mRNA for both
      substance by in situ hybridisation and reverse transcription PCR. mRNA for IL
      1RtI was not found in primordial follicles but was abundant in the granulosa and
      thecal layer in developing follicles with stronger signals in the granulosa
      layer. In the preovulatory and ovulatory follicles, there was a further increase
      in the signal for IL-1RtI mRNA in the thecal layer compared with the granulosa
      layer. Corpora lutea were weakly positive at all stages and atretic follicles
      were largely negative. No mRNA was detected in oocytes of any stage mRNA for IL
      1ra showed a similar distribution to that of IL-1RtI. The changes in distribution
      suggest an action of IL-1 on rat granulosa cells during follicular development
      and on thecal cells during ovulation.

PMID- 9014836
TI  - GH, GH-releasing factor and somatostatin in the growing lamb: sex differences and
      mechanisms for sex differences.
AB  - Factors contributing to sex differences in the somatotrophic axis were
      investigated in growing lambs. In the first experiment, circulating patterns of
      GH in venous blood, pituitary content of GH and GH mRNA, and median eminence (ME)
      contents of GH-releasing factor (GRF) and somatostatin (SRIF) were characterized
      in prepubertal ram and ewe lambs which were pair-fed to remove sex differences in
      feed intake. Mean and baseline plasma GH concentrations, GH pulse amplitude, and
      integrated plasma GH were greater in ram lambs than in ewe lambs, but GH
      interpulse interval did not differ between sexes. The pituitary GH content and ME
      contents of GRF and SRIF were greater in rams than in ewes, but steady-state
      levels of mRNA for GH in the pituitary gland did not differ between sexes. A
      second experiment investigated sex effects on the levels of SRIF in hypophysial
      portal blood, and found that these did not differ between sexes. We concluded
      that the presence of sexually dimorphic patterns of GH secretion in the growing
      lamb is independent of feed-intake differences between sexes. The lack of sex
      differences in circulating patterns of SRIF in portal plasma implies that there
      may be a difference in GRF secretion which may produce sexually dimorphic
      patterns of GH secretion in lamb.

PMID- 9014837
TI  - Regulation of gastrointestinal growth in fetal sheep by luminally administered
      insulin-like growth factor-I.
AB  - Fetuses swallow large volumes of amniotic fluid. Absence of swallowing results in
      gastrointestinal tract (GIT) growth deficits. While it is not yet known to what
      extent the growth factors present in amniotic fluid are involved in GIT ontogeny,
      milk-derived growth factors are considered to be important for neonatal growth.
      Our experiment tested the hypothesis that a luminal growth factor (insulin-like
      growth factor-I, IGF-I) can sustain or promote GIT growth in utero in a model of
      gastrointestinal tract growth retardation. Ten-day infusion of either human
      recombinant IGF-I or vehicle into twin fetal sheep at 80 days gestation via an
      indwelling esophageal catheter resulted in altered GIT growth. Weight of the
      forestomach and small intestine increased. Significant histological changes were
      noted in the proximal small intestine, i.e. the region most exposed to the
      luminal infusion. Mucosal tissues were reduced in size. While the enterocytes in
      the proximal small intestine were generally more mature with regard to the
      ontogeny of the apical endocytic complex (which is responsible for uptake and
      transport of whole peptides), there were also many abnormal cytological features
      present. These included the development of large lysosomal-like inclusion bodies
      and many surfactant-like particles within the apical cytoplasm. Plasma IGF-I
      levels were on average 20% higher in treated siblings, suggesting that luminal
      IGF-I crossed the fetal gut and entered blood. IGF-II levels were not
      significantly affected. These observations are consistent with the suggestion
      that growth factors, which are present in swallowed amniotic fluid, influence
      fetal ontogeny.

PMID- 9014838
TI  - Activation of estrogen receptor-mediated gene transcription by IGF-I in human
      breast cancer cells.
AB  - Estrogen and IGF-I are potent mitogens for most breast cancer cell lines, and
      although their signaling pathways contrast, there is considerable interaction
      between them. Recent evidence indicating that IGF-I can alter estrogen receptor
      (ER) action led us to investigate whether an inhibitor of IGF-I action. IGF
      binding protein-1 (IGFBP-1), could affect transcriptional activation of ER.
      First, we confirmed that tamoxifen (TAM) could inhibit IGF-I-mediated
      proliferation of MCF-7 cells. Although TAM can increase IGFBP-3 expression in MCF
      7 cells, and this binding protein has been shown to be able to inhibit IGF
      action, TAM had no effect on IGF-I-stimulated tyrosine phosphorylation of IGF-I
      receptor or the downstream signaling molecule, insulin receptor substrate-1.
      Therefore, to confirm that IGF-I was affecting transcriptional activation of ER,
      we utilized a gene reporter assay using a single consensus estrogen response
      element (ERE-tk-luc) upstream of luciferase. As expected, estradiol (E2; 1nM)
      increased transcriptional activation three- to fivefold from the ERE in three ER
      positive breast cancer cell lines (MCF-7, ZR-75 and T47D). A 2.5-to 4-fold
      increase was also seen with IGF-I (5 nM). TAM (1 microM) effectively blocked
      activation by E2 and IGF-I, indicating disruption of ER-mediated transcription.
      As expected, human recombinant IGFBP-1 (80 nM) completely inhibited IGF-I
      mediated activation of ER, however, IGFBP-1 also caused a significant decrease in
      E2-mediated activation. We also noticed that IGF-I increased the activity of all
      plasmids that we cotransfected including TATA-luc, SV40-luc and pGL Basic. This
      effect was post-transcriptional, as it was not affected by actinomycin D (2
      micrograms/ml), while we were able to completely inhibit E2-mediated
      transcriptional activation of ERE-tk-luc. Unlike the complete inhibition of ER
      mediated transcriptional activation by actinomycin D, IGF-I-mediated
      transactivation was reduced by only 50%, indicating that the activation by IGF-I
      represented both transcriptional and post-transcriptional effects. This study
      confirmed that IGF-I can cause transcriptional activation of endogenous ER in
      human breast cancel cells, and inhibition of ER action by IGFBP-1 suggests that
      IGF-1 signaling may be necessary for maximal ER activation.

PMID- 9014839
TI  - Effects of adrenal steroids on the concentration of Na(+)-K+ pumps in rat
      skeletal muscle.
AB  - Since adrenal steroids have been shown to upregulate the concentration of Na(+)
      K(+)-ATPase in cardiac muscle, similar effects could be expected in skeletal
      muscle. Following infusion of dexamethasone (0.02-0.1 mg/kg per day) for 7 days
      in 10-week-old rats, the total concentration of [3H]ouabain-binding sites rose by
      up to 22-42% in soleus, extensor digitorum longus, gastrocnemius and diaphragm
      muscle. Dexamethasone produced no or minute changes in the Na(+)-K+ contents of
      skeletal muscle. In contrast, infusion with aldosterone (0.02-0.5 mg/kg per day)
      for 7 days produced hypokalemia and a graded reduction in the K+ content of
      skeletal muscle, which was closely correlated to a downregulation of the
      [3H]ouabain-binding site concentration (r = 0.65-0.70; P < 0.001). The results
      indicate that in skeletal muscle high doses of glucocorticoids upregulate the
      concentration of Na(+)-K+ pumps whereas mineralocorticoids induce a
      downregulation, which is secondary to the concomitant K+ deficiency. Since
      adrenalectomy produced no significant change in [3H]ouabain-binding site
      concentration, basal levels of endogenous adrenal steroids seem to be of minor
      importance for the regulation of Na(+)-K+ pump concentration in skeletal muscle.

PMID- 9014840
TI  - Characterization of insulin glycation in insulin-secreting cells maintained in
      tissue culture.
AB  - Characteristics of cellular insulin glycation were examined in the pancreatic B
      cell line, BRIN-BD11. The extent of insulin glycation increased stepwise during
      72 h of culture at 5.6-33.3 mmol/l glucose, attaining levels up to 27%. Glycation
      of insulin at 33.3 mmol/l glucose was rapid, reaching maximal values within 2 h,
      and not readily reversible during 2 to 24 h of subsequent exposure to 5.6 mmol/l
      glucose. Glycated insulin was readily secreted by BRIN-BD11 cells upon active
      stimulation with glucose and other secretagogues. Cellular insulin glycation was
      decreased by 66-80% by inhibitors of protein glycation, vitamin C, aminoguanidine
      or acetylsalicylic acid. Modulation of insulin-secretory activity of BRIN-BD11
      cells by co-culture at high glucose with diazoxide. L-alanine or glibenclamide
      indicated that long-term stimulation of secretion was associated with a decrease
      in the extent of insulin glycation. Glycation of insulin in vitro was
      substantially less extensive than in BRIN-BD11 cells, although glucose-6
      phosphate and glyceraldehyde-3-phosphate were 1.4- to 2.0-fold more reactive than
      glucose per se. These observations indicate that insulin is readily glycated and
      secreted from insulin-secreting cells under hyperglycaemic conditions in culture.

PMID- 9014841
TI  - Specific expression of haptoglobin mRNA in implantation-stage rabbit uterine
      epithelium.
AB  - A glycoprotein, termed GP42, was previously identified in uterine fluid obtained
      from peri-implantation-stage rabbits. N-terminus amino acid sequencing of
      purified GP42 demonstrated identity through the first 13 amino acids with the
      beta subunit of liver haptoglobin. The present study was undertaken to determine
      if GP42 is indeed identical to haptoglobin and, if so, to determine whether it is
      expressed in the uterus as opposed to being present as a transudate from plasma.
      Reverse transcription-PCR amplification of poly(A)+ RNA prepared from
      implantation-stage rabbit endometrium with GP42- and haptoglobin-specific primers
      yielded a predicted 667 bp cDNA product. Sequence analysis of the cloned cDNA
      confirmed the identity of GP42 with beta-haptoglobin. Northern blot analysis
      demonstrated the specific expression of haptoglobin mRNA in the peri-implantation
      stage endometrium and the absence of its expression in the estrous or day 4
      pseudopregnant endometrium. Non-isotopic in situ hybridization revealed that the
      haptoglobin mRNA was restricted to the epithelium lining the luminal surface and
      mucosal folds of day 6(3/4) pregnant or pseudo-pregnant uteri and that no
      haptoglobin mRNA was detectable in the epithelium of the deep glands or cells of
      the stroma or myometrium. Similarly, in situ hybridization revealed no expression
      of haptoglobin mRNA in any cell types of the estrous uterus. These data establish
      the identity of GP42 with beta-haptoglobin and demonstrate that it is expressed
      in a stage-specific manner just prior to implantation, correlating with uterine
      receptivity to blastocyst implantation. Endometrial GP42 mRNA expression is not
      dependent on the presence of blastocysts.

PMID- 9014842
TI  - Rapid changes in heteronuclear RNA for corticotrophin-releasing hormone and
      arginine vasopressin in response to acute stress.
AB  - The rapid detection of gene activation is important for our understanding of gene
      regulation. We have therefore studied heteronuclear (i.e. nascent) RNA (hnRNA) by
      using 35S-labelled corticotrophin-releasing hormone (CRH) riboprobes and arginine
      vasopressin (AVP) oligo-nucleotide probes directed against intronic and exonic
      sequences of both CRH and AVP transcripts for in situ hybridization studies of
      transcriptional changes during acute stress. CRH and AVP intronic signals (found
      in newly synthesized transcripts) were confined to the nuclei of the
      parvocellular cells in the paraventricular nucleus (PVN) whilst CRH and AVP
      exonic signals (found in both newly formed and mature transcripts) were primarily
      located in the cytoplasm of these cells. AVP hnRNA and mRNA were also present at
      high level, in the magnocellular PVN. The levels of CRH hnRNA and parvocellular
      AVP hnRNA in the PVN were significantly increased 1 and 2 h after the onset of
      restraint. The levels of CRH mRNA on the other hand were not significantly
      increased until 4 h after the onset of restraint. The number of AVP mRNA
      expressing neurons in the medial parvo-cellular cells of the PVN significantly
      increased at 2 h and peaked at 4 h after the onset of stress. In contrast,
      densitometric analysis indicated that the increase in AVP mRNA levels in these
      cells did nor reach significant difference from control until 4 h after the onset
      of restraint. There were no significant changes on AVP hnRNA or AVP mRNA levels
      in the magnocellular subdivision of PVN at any time point after the onset of
      restraint.

PMID- 9014843
TI  - Concentration of GnRH receptor and GnRH receptor mRNA in pituitary tissue of
      orchidectomized sheep: effect of oestradiol, progesterone, and progesterone
      withdrawal.
AB  - The effect of progesterone (P4) and P4 withdrawal on oestradiol (E2)-induced
      change in gonadotrope responsiveness (GR) and concentration of GnRH receptor and
      GnRH receptor mRNA in pituitary tissue of orchidectomized sheep (wethers) was
      determined. Thirty wethers were assigned at random to one of six treatment groups
      (n = 5 animals/group). Wethers received E2 (2 micrograms/h; groups 2, 4, and 6)
      in 10% ethanol-saline (vehicle), or vehicle alone (groups 1, 3, and 5), as a
      continuous infusion for 24 h beginning 7 days after insertion (s.c.) of blank
      (groups 1 and 2) or P4-containing (groups 3-6) implants. The effect of P4
      withdrawal was assessed by removing P4-containing implants at the beginning of
      vehicle (group 5) or E2 (group 6) infusion. Gonadotrope responsiveness (increase
      in serum LH induced by 500 ng GnRH, i.v.) was assessed at the end of infusion. In
      a companion study, anterior pituitary tissue was collected at the end of the 24-h
      infusion period. Infusion of E2 increased (P < 0.05) GR relative to GR noted in
      control wethers receiving vehicle alone. The magnitude of E2-induced augmentation
      of GR was not affected by concurrent administration of P4 or P4 withdrawal.
      Pituitary tissue concentrations of GnRH receptor and GnRH receptor mRNA were
      significantly reduced in wethers implanted with P4. This P4-induced decrease in
      tissue concentration of GnRH receptor and GnRH receptor mRNA was not reversed
      during the 24-h period after P4 withdrawal. Steady-state concentrations of GnRH
      receptor and GnRH receptor mRNA were significantly increased by E2. However, the
      magnitude of oestrogen-induced increase in tissue concentrations of GnRH receptor
      mRNA was not significantly affected by P4 or P4 withdrawal. Conversely,
      concurrent progestin stimulation potentiated the E2-induced augmentation of
      tissue concentrations of GnRH receptor. However, this P4-induced potentiation of
      the oestrogenic response was not evident 24 h after removal of the P4-containing
      implants. Steady-state concentrations of mRNA encoding the LH beta and FSH beta
      subunits were reduced (P < 0.05) by P4. Infusion of E2 had a similar affect.
      These data indicate that prolonged progestin stimulation leads to a decrease in
      tissue concentrations of GnRH receptor and GnRH receptor mRNA. This P4-induced
      suppression of GnRH receptor activity is not reversed within 24 h of P4
      withdrawal. In addition, the increase n steady-state concentrations of GnRH
      receptor and GnRH receptor mRNA induced by E2 is not compromised by concurrent
      progestin stimulation.

PMID- 9014844
TI  - Expression of insulin-like growth factor binding proteins (IGFBPs) in IGFBP-1
      transgenic mice.
AB  - The hepatic and renal expressions of the insulin-like growth factor binding
      proteins (IGFBPs) were examined in transgenic (Tg) mice which overexpress a rat
      IGFBP-1 transgene driven by the phosphoglycerate kinase-1 promoter. There were no
      significant difference in the abundance of serum IGFBPs in Tg and wild-type (Wt)
      mice. Although total hepatic IGFBP-1 mRNA mouse and transgene-derived) levels
      were similar in Tg mice to the levels of mouse IGFBP-1 mRNA in Wt mice on day 1
      of life, in Tg mice only approximately 30% of the IGFBP-1 mRNA was derived from
      transcription of the mouse gene. An age-related decline in hepatic IGFBP-1 mRNA
      levels was apparent in both Tg and Wt mice. Food deprivation resulted in
      increased levels of mouse IGFBP-1 mRNA but the total IGFBP-1 mRNA levels were not
      significantly different in Tg and Wt mice. In the kidney, unlike the liver, IGFBP
      1 mRNA levels in Tg mice were markedly elevated compared with Wt mice and no
      significant decline was seen with age. Northern blots of hepatic and renal RNA
      demonstrated similar levels of IGFBP-3, -4, -5 and -6 mRNAs in Tg and Wt mice.
      From these data we can conclude that in the liver expression of the transgene
      leads to a coordinated reduction in mouse IGFBP-1 mRNA levels.

PMID- 9014845
TI  - Amniotic fluid inhibin-A in chromosomally normal and Down's syndrome pregnancies.
AB  - Recently, inhibin-A has been shown to be a useful new prenatal marker of Down's
      syndrome, significantly increasing detection rates. While the placenta is
      believed to be the major source of inhibin in pregnancy, there are actually very
      limited data available on specific inhibin dimers in pregnancy. Using a sensitive
      and specific ELISA we have measured the inhibin-A content of amniotic fluid (AF)
      to investigate further the biology of inhibin-A in chromosomally normal and
      abnormal pregnancies. AF from 51 Down's syndrome and 161 chromosomally normal
      pregnancies between 16 and 19 weeks of gestation were analysed, blinded as to
      whether the sample was from a Down's syndrome or normal pregnancy. There were no
      sex differences in inhibin-A content in either the control or Down's syndrome
      pregnancies. The median (10-90th percentiles) inhibin-A level in the control
      pregnancies increased from 339.6 (175.2-649.1) pg/ml at 16 weeks to 592.9 (256.4
      1027.3) pg/ml at 19 weeks of gestation. The median (95% confidence interval)
      inhibin-A in the Down's syndrome pregnancies, expressed as multiples of the
      median (MoM) to correct for gestation, was 0.77 (0.68-0.89) MoM, significantly
      lower than the controls (P < 0.001, Mann-Whitney U test). We believe that these
      data are compatible with more than one source of inhibin-A in pregnancy and
      suggest that the fetal membranes may be contributing significantly to AF inhibin
      A content. Further, our data would suggest that the endocrine function of the
      placenta and the other inhibin source(s) are differentially regulated.

PMID- 9014846
TI  - Pulsatile secretion of alpha-MSH and the differential effects of dexamethasone
      and haloperidol on the secretion of alpha-MSH and ACTH in dogs.
AB  - This study was performed to determine whether, in the dog, there is at any time
      pulsatile release of alpha-MSH and whether secretion of ACTH from the pars
      intermedia (PI) contributes to the circulating concentrations of ACTH. The 24-h
      secretory profiles of alpha-MSH, ACTH, and cortisol were determined in eight
      dogs. Plasma samples were obtained at 10-min intervals via an indwelling jugular
      catheter during two 12-h periods. Pulsatile secretion of alpha-MSH was found in
      all dogs, with wide variations in peak height. Plasma alpha-MSH levels were
      usually low (mean 15 pmol/l), but brief, distinct periods of increased plasma
      alpha-MSH concentrations as high as 489 pmol/l were found. Analysis of pulse
      frequency revealed a mean of 4.75 significant alpha-MSH peaks/24 h. The highest
      alpha-MSH peaks were associated with definite changes in the plasma
      concentrations of ACTH. In separate studies, the influence of dexamethasone on
      the 6-h secretory profiles and on the haloperidol-stimulated secretion of alpha
      MSH, ACTH, and cortisol was investigated. In these two studies, plasma ACTH was
      measured by a highly sensitive immunoradiometric assay. Dexamethasone
      pretreatment significantly suppressed the plasma concentrations of ACTH,
      cortisol, and alpha-MSH to 10.3%, 3.9%, and 74.6% respectively. Dexamethasone
      pretreatment also significantly reduced the haloperidol-stimulated secretion of
      ACTH and cortisol, but had no influence on the haloperidol-stimulated secretion
      of alpha-MSH. After the administration of haloperidol to the dexamethasone
      pretreated dogs, there were small increases in the plasma concentrations of ACTH
      and cortisol, the latter being significant. These data demonstrate that alpha-MSH
      is secreted spontaneously in a pulsatile manner in the dog and suggest that the
      canine PI contributes to circulating ACTH concentrations.

PMID- 9014847
TI  - Actions of an IGF-I-enhancing antibody on IGF-I pharmacokinetics and tissue
      distribution: increased IGF-I bioavailability.
AB  - We have previously demonstrated that a specific anti-IGF-I antibody will enhance
      the growth-promoting activity of IGF-I in vivo (Stewart et al. 1993). Since the
      antibody had a modest affinity for IGF-I we suggested that the antiserum might
      protect IGF-I from degradation whilst maintaining it in a bioavailable form. The
      aim of this investigation was to test that hypothesis by determining the plasma
      clearance and tissue distribution of tracer IGF-I in the presence of the
      enhancing anti-IGF-I immunoglobulin (anti-IGF-I Ig) or non-immune immunoglobulin
      (NI Ig). Dwarf rats were treated with saline, NI Ig or anti-IGF-I Ig for 4 days.
      On day 4, 125I-IGF-I (1.6 x 10(7) c.p.m.) was injected into the jugular vein and
      blood sampled over the next 330 min when the rats were killed: samples of liver,
      kidney and skeletal muscle were quickly dissected out. Mean plasma
      trichloroacetic acid (TCA)-precipitable 125I-IGF-I was always significantly
      greater (P < 0.001 for each time point) from anti-IGF-I Ig rats versus the NI Ig
      or saline groups (which exhibited practically identical decay curves), implying
      increased binding capacity for IGF-I in the anti-IGF-I Ig rats. Pharmacokinetic
      parameters were calculated by resolution of the decay curves using a two-phase
      model. The total clearance rate of 125I-IGF-I was significantly decreased (P <
      0.001) by almost twofold in the anti-IGF-I versus the two control groups,
      consistent with the increased binding capacity in the anti-IGF Ig rats. The half
      lives of the faster-decaying phase were not significantly different between
      treatment groups but, surprisingly, that for the slower-decaying phase was
      significantly decreased (P < 0.001) in the anti-IGF-I Ig rats versus the two
      control groups; this may reflect the low affinity of the anti-IGF-I Ig for IGF-I
      and its enhancing properties. The degradation of 125I-IGF-I was significantly
      decreased in animals receiving the anti-IGF-I Ig. In support of this, kidney TCA
      precipitable radioactivity (c.p.m.) was seven-fold less (P < 0.001) in the anti
      IGF-I Ig groups versus the controls, indicative of reduced excretion. Liver TCA
      precipitable radioactivity was increased (P < 0.001) in the anti-IGF-I Ig rats,
      probably due to reticuloendothelial clearance of non-self antibodies: skeletal
      muscle TCA-precipitable radioactivity tended to increase in the anti-IGF-I Ig
      group versus the controls which might indicate increased targeting of IGF-I to
      muscle. Size exclusion chromatography of plasma 15 and 120 min after
      administration of 125I-IGF-I demonstrated a broad peak of radioactivity with a
      molecular mass of 150-300 kDa in the anti-IGF-I Ig-treated rats, which was
      responsible for more than 90% of the eluted radioactivity. This suggests that:
      (1) 125I-IGF-I was bound to the anti-IGF-I Ig and might also be able to associate
      with IGFBPs or (2) the polyclonal antibody might recognise more than one
      antigenic site on IGF-I. These data indicate that the anti-IGF-I Ig was
      protecting IGF-I from degradation, leading to a large plasma pool of IGF-I but
      that IGF-I could be transferred readily from the plasma pool to tissues. We
      suggest that administration of IGF-I in conjunction with a binding molecule
      similar to the antibody described here could provide the basis for effective IGF
      I treatment strategy.

PMID- 9014848
TI  - Effect of the protein phosphatase inhibitor okadaic acid on FSH-induced granulosa
      cell steroidogenesis.
AB  - To address a possible role of type 1 and 2A serine/threonine protein phosphatases
      (PP1 and PP2A) in regulating granulosa cell hormonal responses, we investigated
      the effects of okadaic acid (OA) on FSH- and cAMP-induced steroidogenesis in
      these cells. When added alone (0.01-1 nmol/l), the cell-permeant phosphatase
      inhibitor did not affect progesterone and 3 beta-hydroxysteroid
      dehydrogenase/delta 5-4 isomerase (3 beta-HSD) enzyme activity, whereas when
      added with FSH it dose-dependently augmented (minimal effective dose, 0.1 nmol/l)
      gonadotropin-stimulated steroidogenesis in cultured granulosa cells. A similar
      stimulatory effect of the toxin was observed in cells cultured for 48 h with the
      cell-permeant analogue dibutyryl cAMP (1 mmol/l), or when granulosa cells were
      stimulated with the cAMP-inducing agents cholera toxin (1 microgram/ml),
      forskolin (15 mumol/l) or 1-methyl-3-isobutyl-xanthine (0.1 mmol/l). The observed
      effect of OA on FSH-supported granulosa cell steroidogenesis was not a
      consequence of increased cAMP generation, and time course experiments also
      revealed that a minimal time period of 12 h was necessary for OA (0.1 and 1
      nmol/l) to significantly enhance FSH-induced progesterone and 3 beta-HSD enzyme
      activity. Since OA also inhibits the dephosphorylation of protein kinase C (PKC)
      substrates, we also compared the effect of OA and the PKC activator 12-O
      tetradecanoylphorbol-13-acetate (TPA) on FSH-induced granulosa cell steroidogenic
      activity. While activation of the PKC pathway with the tumor promoter TPA (10
      nmol/l) inhibited progesterone and cAMP accumulation in FSH-stimulated granulosa
      cells, treatment with OA augmented steroidogenesis and did not affect
      gonadotropin-induced cAMP generation. Collectively these results suggest that PP1
      and PP2A may be important in regulating the phosphorylation state of proteins
      implicated in the cAMP-protein kinase A-stimulated steroidogenic activity of
      these cells.

PMID- 9014849
TI  - Presence of pituitary adenylate cyclase-activating polypeptide 38-immuno-like
      material in the brain and ovary of the female crested newt, Triturus carnifex:
      its involvement in the ovarian synthesis of prostaglandins and steroids.
AB  - The presence of pituitary adenylate cyclase-activating peptide (PACAP) 38-immuno
      like material (PACAP 38-IL) in the brain and ovary of the crested newt, Triturus
      carnifex, and its action on ovarian steroidogenesis and prostaglandin synthesis
      were evaluated. The HPLC, brain and ovary extract peaks that eluted like PACAP 38
      were considered PACAP 38-like material. The concentrations of PACAP 38-II in the
      HPLC extracts were measured by RIA. T. carnifex ovary was incubated with PACAP
      38, brain and ovary PACAP 38-IL, and inhibitors of cyclooxygenase (COX),
      adenylate cyclase (AC) and phospholipase C (PLC) for 30 and 60 min. PACAI 38, and
      brain and ovary PACAP 38-IL increased prostaglandin E2 (PGE2) (30 and 60 min),
      and progesterone and corticosterone (60 min), but decreased oestradiol-17 beta
      (60 min). COX and PLC inhibitors counteracted the increases in PGE2, progesterone
      and corticosterone and the decrease in oestradiol-17 beta, and the AC, inhibitor
      also counteracted them except for PGE2. These results suggest that PACAP 38-IL,
      present in T. carnifex brain and ovary, acts on PLC, inducing the increase of
      PGE2 which, in turn, acting on AC, induces increases in progesterone and
      corticosterone and a decrease in oestradiol-17 beta.

PMID- 9014851
TI  - Inhibition of L-692,429-stimulated rat growth hormone release by a weak substance
      P antagonist: L-756,867.
AB  - H2N,D-Arg,Pro,Lys,Pro,D-Phe,Gln,D-Trp,Phe,D-Trp,Leu, Leu,NH2 (L-756,867), a weak
      substance P antagonist, inhibited L-692,429-stimulated GH release from rat
      primary pituitary cells in a dose-dependent manner. At a concentration of 50 nM,
      L-756,867 shifted the dose-response curve of L-692,429-induced GH release to the
      right by about tenfold. It also impaired the ability of L-692,429 to potentiate
      the effect of growth hormone-releasing factor (GRF) on GH release. Substance P (1
      microM) had no effect on basal or L-692,429-stimulated GH release. When tested in
      anesthetized rats, L-756,867 inhibited L-692,429- and growth hormone-releasing
      hexapeptide- (GHRP-6)-stimulated GH secretion in a dose-dependent manner.
      Complete inhibition was observed at an i.v. dose of 100 micrograms/kg of L
      756,867. However, at the same concentration, it had no effect on GRF-induced GH
      secretion D-Lys3-GHRP-6, a GHRP-6 antagonist, had no effect on GHRP-6 or L
      692,429-induced GH secretion even at an i.v. dose of 2 mg/kg. These results
      indicate that L-692,429 and GHRP-6 stimulate GH release both in vitro and in vivo
      via a common receptor and signaling pathway which is different from that of
      substance P in spite of the fact that their effects are inhibited by a weak
      substance P antagonist.

PMID- 9014850
TI  - Adrenal and gonadal function in hypothyroid adult male rats.
AB  - The functional relationship between thyroid, adrenal and gonadal hormones was
      investigated using adult male rats. Hypothyroidism was produced by the
      administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2
      weeks. Plasma concentrations of TSH dramatically increased, whereas plasma
      concentrations of tri-iodothyronine and thyroxine decreased in thiouraciltreated
      rats as compared with euthyroid rats. Hypothyroidism increased basal levels of
      plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH
      for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH
      for corticosterone release decreased. These results indicated that hypothyroidism
      causes adrenal dysfunction in adult male rats. Pituitary contents of LH and
      prolactin decreased in hypothyroid rats as compared with euthyroid rats. In
      addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular
      responsiveness to human chorionic gonadotrophin for testosterone release,
      however, was not different between euthyroid and hypothyroid animals. These
      results indicated that hypothyroidism causes adrenal dysfunction and results in
      hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may
      contribute to the inhibition of LHRH secretion from the hypothalamus, possibly
      mediated by excess CRH.

PMID- 9014852
TI  - Maternal diabetes induces upregulation of hepatic insulin-like growth factor
      binding protein-1 MRNA expression, growth retardation and developmental delay at
      the same stage of rat fetal development.
AB  - Since maternal diabetes is associated with fetal growth abnormalities in humans
      and rats, effects of maternal diabetes on fetal expression of genes regulating
      growth are of interest. Increased expression of Insulin-Like Growth Factor
      Binding Protein-I (IGFBP-1) is associated with several examples of growth
      retardation and is upregulated in response to diabetes. As we have shown
      previously, IGFBP-1 expression is upregulated in gestational day (GD) 14 rat
      fetuses in response to maternal diabetes. Here we analyze the effect of
      streptozotocin-induced maternal diabetes on IGFBP-1 mRNA expression during GD12
      16 of rat fetal development, using in situ hybridization. IGFBP-1 mRNA was more
      abundant in GD12-14 fetal livers from diabetic dams than in livers of age-matched
      controls. This upregulation is not due to the approximately 1-day fetal
      developmental delay associated with maternal diabetes, as there is no gross
      difference in the level of IGFBP-1 mRNA in GD13 vs GD12 or GD14 vs GD13 control
      fetal livers. At GD15-16, however, we detected little difference in IGFBP-1
      expression between experimental and control fetuses. This transient period of
      maternal diabetes-stimulated IGFBP-1 mRNA expression (GD12-14) is coincident with
      the sensitive period for maternal diabetes-induced defects in fetal growth and
      development, suggesting that IGFBP-1 is involved in the regulation of fetal
      growth and development in response to the maternal condition.

PMID- 9014853
TI  - The conceptual and practical impact of Ki-ras mutation in colorectal neoplasia.

PMID- 9014854
TI  - Ki-ras mutations in adenomas: a characteristic of cancer-bearing colorectal
      mucosa.
AB  - Activating mutations in the Ki-ras2 oncogene are frequently observed in sporadic
      colorectal adenomas and their incidence is reported to rise in large and
      tubulovillous adenomas to values close to those in carcinomas. This study shows
      that this property is a feature of adenomas growing in large bowel that has
      already demonstrated its propensity to engender malignant tumours: i.e., bowel in
      which there is a synchronous carcinoma. Adenomas from cancer-free bowel do not
      share this high incidence of Ki-ras mutations. This difference in mutation
      incidence between adenomas from cancer-free and cancer-bearing patients does not
      appear to derive from sampling bias relative to adenoma size, site, or patient
      age, nor is it found in another gene (APC) known to be of importance in adenoma
      formation. Large, dysplastic adenomas from cancer-bearing bowel, however, are
      particularly liable to carry Ki-ras mutations when they arise in patients over 70
      years old. The observations suggest that the role of Ki-ras mutations may be more
      subtle than merely enhancing adenoma growth. Adenoma cells of cancer-prone
      individuals may suffer more mutational events than those in persons selected as
      cancer-free.

PMID- 9014855
TI  - Prognostic significance of p53 abnormalities in colorectal carcinoma detected by
      PCR-SSCP and immunohistochemical analysis.
AB  - Abnormalities in the p53 tumour suppressor gene and in the expression of its
      protein are common in colorectal carcinoma. The prognostic significance of these
      p53 abnormalities was studied in 66 patients with colorectal cancer, followed for
      more than 10 years. Single-strand conformation polymorphism (SSCP) analysis was
      used to detect alterations in exons 5-8 of the p53 gene. Paraffin sections were
      examined immunohistochemically for p53 overexpression with the monoclonal
      antibody DO-7 (Dako) both with and without microwave antigen retrieval.
      Abnormalities of the p53 gene were found in 41 per cent of cases by SSCP
      analysis. Outcome was unrelated to SSCP abnormalities (P = 0.19), except for the
      Dukes' A and B subgroup, where decreased survival was found in cases with
      abnormal SSCP (P = 0.01). Overexpression of p53 protein was seen by
      immunohistochemistry in 47 per cent of cases without, and in 52 per cent of cases
      with microwave antigen retrieval. Immunohistochemical overexpression of p53
      protein either with or without microwave antigen retrieval was an independent
      prognostic indicator of poor survival. These results suggest that for routine
      purposes, immunohistochemical detection of the p53 protein product may be more
      useful than SSCP analysis of the encoding p53 gene in identifying those at high
      risk of colorectal cancer recurrence and death.

PMID- 9014856
TI  - Allelotype of adenoma and differentiated adenocarcinoma of the stomach.
AB  - The molecular mechanism of gastric tumourigenesis has not yet been clarified,
      although investigators have postulated that differentiated adenocarcinoma may
      arise from pre-existing adenoma, similarly to the colorectal adenoma-carcinoma
      sequence. An allelotype analysis has been performed to identify chromosomal
      regions which are frequently deleted in gastric tumours and to examine the
      significance of the adenoma-carcinoma sequence in gastric tumourigenesis. Forty
      five gastric tumours, 20 adenomas, and 25 differentiated adenocarcinomas were
      examined for loss of heterozygosity (LOH) using 39 microsatellite markers
      covering each non-acrocentric chromosome arm. Frequent LOH in the adenocarcinomas
      was observed on chromosomes 2q (33 per cent), 4p (33 per cent), 5q (50 per cent),
      6p (33 per cent), 7q (43 per cent), 11q (36 per cent), 14q (38 per cent), 17p (45
      per cent), 18q (36 per cent), and 21q (40 per cent). In contrast, the incidence
      of LOH in adenomas did not exceed 10 per cent at any of the loci examined. In
      addition to the p53 gene on 17p and the DCC gene on 18q, which are known to be
      frequently deleted in differentiated adenocarcinomas of the stomach, other
      unknown tumour suppressor genes on the above-mentioned chromosomes may also be
      inactivated. These observations suggest that the adenoma-carcinoma sequence is
      not a major pathway in gastric tumourigenesis.

PMID- 9014857
TI  - Properties of HPV-positive and HPV-negative anal carcinomas.
AB  - Evidence of human papillomavirus (HPV) can be found in up to 85 per cent of anal
      carcinomas. In the vulva, a discrete subset of HPV-positive carcinomas which show
      koilocytic morphology and distinct clinical features has recently been identified
      (warty carcinoma). The morphological and prognostic features of HPV-positive and
      HPV-negative anal carcinomas were compared in this study of the tumour
      distribution of HPV DNA. Vulval and anal neoplasia are similar in many ways and
      we have also looked to see if their similarity extends to 'warty' morphology in
      relation to HPV status. Thirty-five resection specimens of anal carcinoma were
      examined with biotin-labelled probes for HPV 6, 11, 16, and 18 DNA, using a non
      isotopic in situ hybridization (ISH) technique. No tumour was found to contain
      HPV 6, 11, or 18. Twenty-four (72 per cent) showed positivity for HPV 16 DNA.
      Staining was homogeneous and independent of local squamous, basaloid, or ductal
      differentiation. The majority of tumours showed staining suggestive of episomal,
      non-productive HPV infection. HPV-positive tumours were more likely to occur in
      the anal canal than perianally and to show a mixed squamous and basaloid
      appearance. No difference between the two groups was found in patient age,
      presence of adjacent dysplasia, ductal differentiation, or prognosis. There was
      no correlation between condylomatous tumour morphology and HPV 16 DNA positivity;
      thus, a subset equivalent to vulval warty carcinoma could not be identified.

PMID- 9014858
TI  - c-Src protein expression is increased in human breast cancer. An
      immunohistochemical and biochemical analysis.
AB  - In human breast cancer, c-Src activity is elevated compared to normal breast
      tissue. It is not yet known whether this increase in c-Src activity is
      accompanied by an increase in c-Src protein expression. In this study, c-Src
      activity and protein expression were determined in a series of human breast
      cancers and in normal breast tissue, using immune complex kinase assays and
      immunoblotting. As the heterogeneity of breast cancer is not taken into account
      in these biochemical experiments, immunohistochemistry was also used to
      distinguish between normal and malignant cells. In human breast cancers, the c
      Src activity is increased 4- to 30-fold, compared with normal breast tissue. This
      enhanced activity is accompanied by an increase in c-Src protein expression, as
      shown by both immunoblotting and immunohistochemistry. Immunohistochemistry
      indicates that the majority of c-Src appears to be concentrated around the
      nucleus in malignant cells, whereas in normal cells, it is distributed more
      evenly in the cytoplasm. These data confirm that c-Src activity is increased in
      human breast cancer. In addition, this study provides strong immunohistochemical
      evidence that the c-Src protein is also overexpressed, enabling a distinction to
      be made between normal and malignant cells.

PMID- 9014859
TI  - Immunoreactivity for hepatocyte growth factor/scatter factor and its receptor,
      met, in human lung carcinomas and malignant mesotheliomas.
AB  - Paraffin sections from 29 lung carcinomas (28 primary and 1 metastatic) and 9
      pleural malignant mesotheliomas were immunostained with antisera to human
      hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, met. For
      HGF/SF, immunoreactivity was demonstrated in all 9 mesotheliomas, 9 of 12
      adenocarcinomas, and 7 of 10 squamous cell carcinomas. None of seven cases of
      small cell anaplastic carcinoma was positive. The adenocarcinomas frequently
      showed enhanced luminal staining, suggesting possible secretion of HGF/SF, and
      this pattern of staining was also seen occasionally in bronchial epithelium
      adjacent to the tumour. Stromal fibroblasts also showed immunoreactivity for
      HGF/SF in 6/8 cases of mesothelioma but in only 3/12 adenocarcinomas, 1/10
      squamous cell carcinomas, and 1/4 small cell anaplastic carcinomas. All tumours
      stained for met, usually strongly. The staining was mainly cytoplasmic in nature,
      but some plasma membrane staining was usually evident. Adenocarcinomas showed
      strong luminal membrane staining, as did adjacent, histologically normal
      bronchial epithelium. This study demonstrates the presence of HGF/SF and met in
      most of the tumour types described, particularly mesotheliomas, and suggests that
      the HGF/SF/met signalling system may play a role in the development of these
      tumours, either by autocrine or by paracrine mechanisms.

PMID- 9014861
TI  - The presence of cytokines in Langerhans' cell histiocytosis.
AB  - Langerhans' cell histiocytosis (LCH) is characterized by an accumulation and/or
      proliferation of cells with a Langerhans' cell (LC) phenotype. The aetiology and
      pathogenesis of LCH are unknown; it is suggested that LCH is caused by an
      immunological dysregulation. Production of cytokines is a central feature of
      immunological regulation. LCH lesions and normal LCs were studied for the
      presence of cytokines known to influence the functioning of LCs: IL-1 alpha, IL-1
      beta, IL-4, GM-CSF, IFN-gamma, TGF-alpha, TGF-beta, bFGF, and TNF-alpha.
      Cytokines were abundantly present within LCH lesions; LCH cells stained for IL-1
      alpha, IL-1 beta, IL-4, GM-CSF, TGF-alpha, TGF-beta, TNF-alpha, and IFN-gamma.
      Macrophages, lymphocytes, eosinophil granulocytes, and, surprisingly,
      multinucleated giant cells were also sources of cytokines. These results suggest
      that cytokines play a prominent role in the pathogenesis of LCH and may explain
      phenomena that often occur in LCH, such as osteolysis and fibrosis and the
      recruitment of typical inflammatory infiltrates. The results also suggest that a
      'down-regulatory' signal is lacking in LCH, resulting in an accumulation and/or
      proliferation of abnormal LCs.

PMID- 9014860
TI  - Cyclin D1 overexpression in non-small cell lung carcinoma: correlation with Ki67
      labelling index and poor cytoplasmic differentiation.
AB  - Cyclin D1 is part of the molecular system regulating the cell cycle G1 to S
      transition point. Its overexpression, a common finding in carcinomas of the
      breast, oesophagus, and head and neck, has also been demonstrated in a high
      percentage of non-small cell lung carcinomas (NSCLCs). The role of cyclin D1 in
      NSCLC has been studied by correlating its immunoreactivity with the Ki67
      labelling index in paraffin-embedded, autoclaved surgical samples of 56 NSCLC
      cases. In addition, flow cytometric determination of ploidy and cell cycle status
      was carried out on 172 fresh tumour samples from the same cases. Twenty-four
      (42.8 per cent) NSCLCs showed positive cyclin D1 immunostaining, a finding which
      showed no relationship to ploidy pattern, cell cycle phase, histological subtype,
      or lymph node metastasis, but was significantly associated with the Ki67
      labelling index (P = 0.03) and with poor cytoplasmic differentiation (P = 0.01).
      Cyclin D1-positive nuclei were abundant in poorly differentiated zones and absent
      in the best differentiated areas, particularly in heavily keratinized fields.
      These data indicate that in NSCLC, cyclin D1 overexpression is not only
      associated with a high cell proliferation rate, but also seems to play a role in
      the process of tumour differentiation.

PMID- 9014862
TI  - Altered expression of TGF alpha and TGF beta 1 in the mucosa of the functioning
      pelvic ileal pouch.
AB  - The mucosa of the functioning pelvic ileal pouch undergoes loss of villous height
      and an increase in crypt cell proliferation as an adaptive response to its new
      luminal environment. These changes can occur in the absence of inflammation and
      could be mediated by growth factors such as transforming growth factors alpha and
      beta 1 (TGF alpha and TGF beta 1). Expression of TGF alpha and TGF beta 1
      messenger RNA (mRNA) and protein was determined by in situ hybridization and
      immunohistochemistry in sections of terminal ileum taken at the time of pouch
      formation and of subsequent pouch biopsies from 14 patients (total of 90
      specimens). Crypt cell proliferation was assessed using the monoclonal antibody
      MIB-1. As ileal pouch mucosa underwent loss of villous height and crypt
      hyperplasia, epithelial expression of TGF alpha mRNA and protein decreased. In
      contrast, TGF beta 1 mRNA and protein were abundant in both normal and flat
      mucosa. Epithelial expression of TGF beta 1 protein was maximal in flat, inflamed
      biopsies. These results suggest that although altered expression of TGF alpha and
      TGF beta 1 mRNA and protein may play some part in the regulation of the adaptive
      response in ileal pouch mucosa, TGF alpha does not have a direct, positive role
      in the regulation of crypt cell proliferation.

PMID- 9014863
TI  - Differential growth of N- and S-type human neuroblastoma cells xenografted into
      scid mice. correlation with apoptosis.
AB  - This study concerns the role of apoptosis in the growth of human neuroblastomas
      transplanted into immunodeficient SCID mice. Human neuroblastoma cell lines may
      consist of one or more distinct phenotypes including the neural 'N-type' and flat
      substrate-adherent 'S-type'. A differential phenotype-specific proliferation was
      apparent among S- and N-type cell clones transplanted into SCID mice when
      compared with the wild-type SK-N-BE(2) cell line. This differential growth
      capacity of the tumours was correlated with spontaneous apoptosis. Another SK-N
      BE(2)-derived cell line (TGA), displaying high levels of apoptosis upon stable
      transfection with the full length 'tissue' transglutaminase (tTG) cDNA, was
      unable to induce tumour development when xenografted into SCID mice. To support
      these observations, the expression of apoptosis-related genes (i.e., bcl-2, p53,
      and tTG) in the various neuroblastomas was also investigated.

PMID- 9014864
TI  - Foam cell apoptosis and the development of the lipid core of human
      atherosclerosis.
AB  - A characteristic feature of the advanced atherosclerotic lesion is the acellular
      lipid core, which appears to result at least partly from the death of macrophage
      foam cells. This study shows that foam cell death at the edge of the lipid core
      includes both necrosis and apoptosis and that remnants of apoptotic nuclei are
      present within the lipid core. Apoptotic cells were identified by transmission
      electron microscopy and by nick end-labelling using terminal deoxynucleotidyl
      transferase (TUNEL). Some TUNEL-positive cells also expressed proliferating cell
      nuclear antigen (PCNA). The cause of foam cell death in atherogenesis is unknown,
      but oxidized low-density lipoprotein (LDL) can cause macrophage apoptosis in
      vitro and might therefore play a role in the formation and enlargement of the
      lipid core.

PMID- 9014865
TI  - Morphological and biochemical evidence for apoptosis in the terminal hypertrophic
      chondrocytes of the growth plate.
AB  - The purpose of this study was to investigate the mechanism of cell death in
      chondrocytes of the growth plate. In the degenerative chondrocyte zone of the
      growth plate, apoptotic chondrocytes were defeated by the in situ nick end
      labelling method, by DNA analysis in agarose gel, and by electron microscopy. The
      results of the in situ nick end labelling method and the occurrence of a ladder
      pattern of DNA in agarose gel analysis indicated the activation of endogenous
      endonucleases, resulting in DNA fragmentation. Electron micrographs showed the
      early morphological changes associated with apoptosis. This report presents both
      morphological and biochemical evidence for apoptosis in the terminal hypertrophic
      chondrocytes of the growth plate. These data suggest that apoptosis of
      degenerative chondrocytes may play an important role in the control of normal and
      pathological endochondral ossification.

PMID- 9014866
TI  - Alterations in mast cell proteinases and protease inhibitors in the progress of
      cutaneous herpes zoster infection.
AB  - The possible involvement of mast cell proteases in the cutaneous inflammation of
      herpes zoster was studied histochemically in ten patients. Mast cell tryptase and
      chymase bioactivities were demonstrated enzyme-histochemically. The localization
      of protease inhibitors as well as tryptase and chymase proteins in mast cells was
      established using a sequential double-staining method which first demonstrated
      bioactive tryptase or chymase, followed by immunohistochemical identification of
      these antigens. Biopsies were taken from involved vesicular and erythematous
      skin, as well as from normal healthy-looking skin. Tryptase-bioactive mast cells
      were significantly lower in number in the upper, but not in the deeper dermis of
      vesicular skin (68 +/- 37 cells/mm2, mean +/- SD) when compared with either
      healthy-looking (97 +/- 38) or erythematous skin (105 +/- 36) (t-test, P <
      0.005). In contrast, chymase-bioactive mast cells were significantly reduced in
      number both in erythematous skin (44 +/- 20, P < 0.02) and even more so in
      vesicular skin (26 +/- 20, P < 0.0005) when compared with healthy-looking skin
      (64 +/- 27). The percentage of alpha 1-antitrypsin -immunoreactive and alpha 1
      antichymotrypsin-immunoreactive mast cells in the upper dermis increased steadily
      from the values in healthy-looking skin (37.9 +/- 18.8 and 82.5 +/- 21.6 per
      cent) to those in erythematous (64.4 +/- 16.4 and 93.5 +/- 7.9 per cent) and
      vesicular skin (75.2 +/- 10.2 and 96.4 +/- 4 per cent). A novel finding was that
      cells showing tryptase immunoreactivity but no enzyme activity were found in two
      out of nine erythematous skin specimens and in four out of seven vesicular
      specimens. In healthy-looking skin, all cells with chymase immunoreactivity also
      displayed chymase bioactivity, but only 53.2 +/- 24.25 per cent of these mast
      cells in erythematous lesions and 44.4 +/- 15.9 per cent in vesicular lesions
      showed chymase bioactivity, suggesting inactivation of chymase by protease
      inhibitors. These results show prominent alterations in mast cell proteinases and
      protease inhibitors, indicating that these enzymes participate in the cutaneous
      inflammation due to herpes zoster.

PMID- 9014867
TI  - Cell type-specific mechanisms regulate hepatitis B virus transgene expression in
      liver and other organs.
AB  - Intracellular expression of hepatitis B virus (HBV) was analysed in transgenic
      HBV mouse lines designated G7 and G26, the former lacking hepatitis B surface
      antigen (HBsAg) promoters. HBsAg mRNA expression was greater in the G26 line than
      in the G7 line, although in situ hybridization showed a qualitatively similar
      expression pattern in specific cell types. HBsAg mRNA was most abundant in
      hepatocytes, followed in magnitude by proximal renal tubular epithelial cells,
      pancreatic acinar cells, and epithelial cells of the gastric, small intestinal,
      and bronchiolar mucosae. In biliary epithelial cells, brain, spleen, large
      intestine, testis, heart, and skeletal muscle, HBsAg mRNA was undetectable. In
      cell transfection assays, the HBV enhancer/preS1 promoter efficiently expressed a
      luciferase reporter with appropriate upregulation by HNF-3 alpha and C/EBP alpha
      transcription factors in hepatocyte-derived cells but not in non-parenchymal
      epithelial liver cells or fibroblasts. These results suggest that cell-type
      specificity of HBV expression is regulated by interactions between viral elements
      and cellular transactivators. Variable expression of G7 and G26 HBV transgenes in
      epithelial cells combined with differences in transgene expression in similar
      sets of cells suggests at least two levels of regulation: one directing cell
      specificity of HBV expression and the other governing quantitative expression of
      HBV mRNA.

PMID- 9014868
TI  - Expression of vascular cell adhesion molecule-1 in murine hearts with acute
      myocarditis caused by coxsackievirus B3.
AB  - Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of
      the myocardial cell damage involved in viral myocarditis. Using a murine model of
      acute myocarditis caused by Coxsackievirus B3 (CVB3), perforin-expressing killer
      cells have been shown to infiltrate the heart, and intercellular adhesion
      molecular-1 (ICAM-1) together with major histocompatibility complex (MHC) antigen
      was induced on myocardial cells in acute viral myocarditis. To clarify the
      immunological mechanisms in more detail, the expression of vascular cell adhesion
      molecular-1 (VCAM-1) has been examined in the heart of acute myocarditis and on
      cultured cardiac myocytes treated with interferon-gamma (IFN-gamma) and tumour
      necrosis factor-alpha (TNF-alpha). The effects of in vivo antibody treatment to
      VCAM-1 on myocardial damage involved in acute myocarditis were also analysed.
      CVB3-induced myocarditis resulted in enhanced expression of VCAM-1 on myocardial
      cells. VCAM-1 expression was also induced on cultured cardiac myocytes by
      treatment with IFN-gamma and TNF-alpha. The in vivo antibody treatment to VCAM-1
      decreased the myocardial damage to some extent, but the effects were not
      statistically significant. These data suggest that the expression of VCAM-1 on
      myocardial cells may play at least a partial role in the myocardial damage
      involved in acute viral myocarditis.

PMID- 9014869
TI  - Extraction and protein sequencing of immunoglobulin light chain from formalin
      fixed cerebrovascular amyloid deposits.
AB  - Substantial amounts of a single protein have been extracted into electrophoresis
      sample buffer from archived formalin-fixed brain blood vessels, taken from a case
      of cerebral amyloidosis. Cyanogen bromide cleavage and tryptic digestion of the
      protein on Western blots allowed amino acid sequences from three resultant
      peptides to be determined. Comparison of these peptides with database sequences
      identified the extracted protein as being derived from an immunoglobulin light
      chain. This is the first demonstration of amino acid sequencing of a polypeptide
      extracted from formalin-fixed tissue. This case also appears to be unique, since
      primary cerebrovascular amyloidosis involving immunoglobulin light chains has not
      been previously described. The amyloid protein had clearly resisted formalin
      fixation; it is possible that this resistance occurred because the protein was
      deposited in large amounts as insoluble densely packed aggregates, which may
      exclude infiltration of the formalin. This technique may therefore have
      applications in the post-mortem diagnosis of amyloidoses and in the purification
      of other amyloids.

PMID- 9014870
TI  - AM-3K, a novel monoclonal antibody allegedly specific for tissue macrophages,
      also reacts with vascular endothelial cells in the atherosclerotic plaque.

PMID- 9014871
TI  - Specificity of the EWS/WT1 gene fusion for desmoplastic small round cell tumour.

PMID- 9014872
TI  - Organs for transplantation: should the UK follow Belgium?

PMID- 9014873
TI  - The future for electronic journals.

PMID- 9014874
TI  - Presumed consent to organ donation: 10 years' experience in Belgium.

PMID- 9014875
TI  - Nitric oxide 9 years on.

PMID- 9014877
TI  - Endogenous neurotoxins relevant to schizophrenia.

PMID- 9014876
TI  - Helicobacter pylori: the cancer link.

PMID- 9014879
TI  - Paediatric rectal prolapse in Rwanda.
AB  - During the 1994 crisis in Rwanda, a high incidence of full-thickness rectal
      prolapse was noted among the refugee children in the south-west of the country.
      The prolapses arose as a result of acute diarrhoeal illness superimposed on
      malnutrition and worm infestation. We used a modification of the Thiersch wire
      technique in 40 of these cases during two months working in a refugee camp. A
      catgut pursestring was tied around the anal margin under local, regional or
      general anaesthesia. This was effective in achieving short-term control of full
      thickness prolapse until the underlying illness was corrected. Under the
      circumstances, no formal follow-up could be arranged; however, no complications
      were reported and only one patient presented with recurrence.

PMID- 9014878
TI  - Do community hospitals reduce the use of district general hospital inpatient
      beds?
AB  - Community hospitals have been supported by the general public and by
      professionals as one means of increasing choice between local, low technology,
      care and high technology care at the district general hospital. However, there is
      no information on the impact of community hospitals on district general hospital
      use subsequent to NHS and community care reforms. Examination of routinely
      gathered activity data in the Bath Health District revealed that availability of
      community hospital beds was associated with reduced use of central inpatient
      services in the city of Bath. The reduction was most apparent for medical and
      geriatric beds. Decrease in the use of surgical beds was small. However, total
      inpatient bed use (including central and community hospital beds) was higher in
      the population with access to community hospital beds. We conclude that community
      hospitals offer one option for accessible health care and, as such merit
      systematic evaluation of costs and benefits. This study presents some evidence
      that savings could be achieved through improved efficiency.

PMID- 9014880
TI  - Educating psychiatric patients about their treatment: do fact sheets work?
AB  - Psychiatric patients are sometimes given fact sheets about their treatment but
      the benefits of these are uncertain. We tested three strategies in three cohorts
      of psychiatric inpatients--fact sheets alone, fact sheets and subsequent
      discussion, and control. Knowledge of medication was assessed by questionnaire.
      For various reasons, only 33 of the 77 patients were included in the study or
      analysis. Of the patients who had been given fact sheets, 87% independently read
      them and reported finding them helpful whilst all asked for more information.
      Receiving a fact sheet alone had no significant effect, whereas having discussed
      it with a health care professional was associated with a significant increase in
      knowledge about medication. Patients receiving fact sheets selectively learned
      more about side-effects than about drug action or precautions. This strategy for
      patient education could be used by ward nurses and deserves further evaluation.

PMID- 9014881
TI  - Anogenital lichen sclerosus in women.
AB  - A study of 350 women with lichen sclerosus, originally made to elucidate the
      relationship between lichen sclerosus and autoimmunity, led to the amassing of a
      considerable amount of clinical material. Our review is confined to those with
      anogenital lesions (342), supplemented by some new cases (15), giving a total of
      357 women with biopsy proven lichen sclerosus. It demonstrates the wide age range
      of the condition, the association with morphoea and lichen planus and the
      occurrence of squamous cell carcinoma in some cases. It also shows that
      inappropriate surgery has continued to be carried out for benign disease.

PMID- 9014882
TI  - Management of lichen sclerosus and intraepithelial neoplasia of the vulva in the
      UK.
AB  - Women with vulval intraepithelial neoplasia (VIN), lichen sclerosus (LS) and
      Paget's disease are referred either to gynaecologists or to dermatologists. We
      have ascertained the caseloads, referral patterns and treatment modalities used
      in the two specialties. A postal questionnaire was sent to 540 consultant
      gynaecologists and 225 consultant and senior registrar members of the British
      Association of Dermatologists. 350 gynaecologists and 161 dermatologists returned
      completed questionnaires. The workload of LS and Paget's disease was evenly
      distributed, with 54% of dermatologists and 58% of gynaecologists seeing more
      than six cases of LS per annum and less than 1% seeing more than five cases of
      Paget's disease. 92% of responding gynaecologists saw at least one case of VIN
      per year whereas 43% of dermatologists saw no cases. Patients with VIN and
      Paget's were referred to gynaecologists for treatment by 66% of dermatologists.
      Both groups are equally prepared to treat LS. Indications for treatment of VIN
      and LS were suspicion of invasion and symptoms. Local excision of VIN is the
      treatment of choice by both gynaecologists and dermatologists. LS is
      predominantly treated with topical steroids but gynaecologists also use topical
      oestrogen and testosterone. The great majority of responders favoured
      establishing a national register to study the outcome of vulval lesions.

PMID- 9014884
TI  - Group B streptococcal infection in a mother and her baby.

PMID- 9014883
TI  - Congenital abnormality of the liver initially misdiagnosed as splenic haematoma.

PMID- 9014885
TI  - Idiopathic rhabdomyolysis.

PMID- 9014886
TI  - Multiple myeloma presenting as recurrent ureteric obstruction.

PMID- 9014887
TI  - Intraprostatic cyst--a cause of bladder outflow obstruction.

PMID- 9014888
TI  - Spontaneous rupture of the spleen secondary to metastatic teratoma.

PMID- 9014889
TI  - The Countess Margaret of Henneberg and her 365 children.
AB  - According to an obscure medieval legend, the Countess Margaret of Henneberg, a
      notable Dutch noblewoman, gave birth to 365 children in the year 1276. The
      haughty Countess had insulted a poor beggar woman carrying twins, since she
      believed that a pair of twins must have different fathers, and that their mother
      must be an adultress. She was punished by God, and gave birth to 365 minute
      children on Good Friday, 1276. The Countess died shortly after, together with her
      offspring, in the village of Loosduinen near The Hague. The Countess and her
      numerous brood were frequently described in historical and obstetrical works. To
      this day, a memorial tablet and two basins, representing those in which the 365
      children were baptized, are to be seen in the church of Loosduinen.

PMID- 9014891
TI  - Addenbrooke's art and murals.

PMID- 9014890
TI  - Herbs: useful plants.

PMID- 9014892
TI  - Should we buy liaison psychiatry?

PMID- 9014893
TI  - Should we buy liaison psychiatry?

PMID- 9014894
TI  - Should we buy liaison psychiatry?

PMID- 9014896
TI  - Should we buy liaison psychiatry?

PMID- 9014895
TI  - Should we buy liaison psychiatry?

PMID- 9014898
TI  - Epidural anaesthesia and urinary dysfunction.

PMID- 9014897
TI  - Science versus quackery.

PMID- 9014899
TI  - Acute mountain sickness.

PMID- 9014900
TI  - Creativity and mental health.

PMID- 9014901
TI  - Have a pig's heart?

PMID- 9014903
TI  - Identification of brain region for coordinating speech articulation.

PMID- 9014902
TI  - Oral vaccines against cholera: lessons from Vietnam and elsewhere.

PMID- 9014904
TI  - Nasal benzodiazepines for management of acute childhood seizures?

PMID- 9014905
TI  - New treatments for alopecia areata.

PMID- 9014906
TI  - Will glycosylated haemoglobin replace the oral glucose-tolerance test?

PMID- 9014907
TI  - London's mental health problems.

PMID- 9014908
TI  - Randomised trial of plasma exchange, intravenous immunoglobulin, and combined
      treatments in Guillain-Barre syndrome. Plasma Exchange/Sandoglobulin Guillain
      Barre Syndrome Trial Group.
AB  - BACKGROUND: The relative efficacy of plasma exchange (PE) and intravenous
      immunoglobulin (IVIg) for the treatment of Guillain-Barre syndrome has not been
      established. We compared PE with IVIg, and with a combined regimen of PE followed
      by IVIg, in an international, multicentre, randomised trial of 383 adult patients
      with Guillain-Barre syndrome. METHODS: The patients were randomly assigned PE
      (five 50 mL/kg exchanges over 8-13 days), IVIg (Sandoglobulin, 0.4 g/kg daily for
      5 days), or the PE course immediately followed by the IVIg course. The inclusion
      criteria were severe disease (aid needed for walking) and onset of neuropathic
      symptoms within the previous 14 days. Patients were followed up for 48 weeks.
      FINDINGS: Four patients were excluded because they did not meet the randomisation
      criteria. All the remaining 379 patients were assessed for the major outcome
      criterion-change on a seven-point disability grade scale-by an observer unaware
      of treatment assignment, 4 weeks after randomisation. At that time, the mean
      improvement was 0.9 (SD 1.3) in the 121 PE-group patients, 0.8 (1.3) in the 130
      IVIg-group patients, and 1.1 (1.4) in the 128 patients who received both
      treatments (intention-to-treat analysis). None of the differences between the
      groups for this major outcome criterion was significant. The difference between
      PE alone and IVIg alone was so small that a 0.5 grade difference was excluded at
      the 95% level of confidence. There was no significant difference between any of
      the treatment groups in the secondary outcome measures: time to recovery of
      unaided walking, time to discontinuation of ventilation, and trend describing the
      recovery from disability up to 48 weeks. There was a non-significant trend
      towards a more favourable outcome on some outcome measures with combined
      treatment. INTERPRETATION: In treatment of severe Guillain-Barre syndrome during
      the first 2 weeks after onset of neuropathic symptoms, PE and IVIg had equivalent
      efficacy. The combination of PE with IVIg did not confer a significant advantage.

PMID- 9014909
TI  - Field trial of a locally produced, killed, oral cholera vaccine in Vietnam.
AB  - BACKGROUND: Several studies have shown that orally administered killed cholera
      vaccines are safe and protective in populations at risk of cholera in developing
      countries. However, these vaccines have not been adopted for use in developing
      countries because of their expense and limited efficacy in young children. We
      have tested an inexpensive, killed whole-cell cholera vaccine developed and
      produced in Vietnam. METHODS: The efficacy of the vaccine was assessed in a large
      scale, open field trial in people at least 1 year old residing in 22,653
      households in the central coastal city of Hue. Alternate households were assigned
      vaccine (67,395 people; two doses per person) or no vaccine (67,058 people).
      Surveillance for cholera was conducted in all Ministry of Health facilities
      serving this population. Analysis was by intention to treat. FINDINGS: During an
      outbreak of El Tor cholera 8-10 months after vaccination, 37 cases of cholera
      requiring inpatient care occurred among age-eligible people allocated to the
      vaccine group, and 92 cases among age-eligible people allocated to the no-vaccine
      group (protective impact 60% [95% CI 40-73]). Among the 51,975 people who
      received the complete two-dose vaccine regimen, the protective efficacy was 66%
      (46-79): in this subset, the protective efficacy was similar for children aged 1
      5 years (68%) and for older people (66%). INTERPRETATION: These findings suggest
      that oral killed whole-cell vaccines can confer substantial protection against El
      Tor cholera in young children, who are at highest risk of cholera in endemic
      settings. An inexpensive, locally produced, and effective oral cholera vaccine
      may be within reach of the limited health-care budgets of poor countries with
      endemic cholera, if our findings can be replicated in a randomised double-blind
      trial.

PMID- 9014910
TI  - Susceptibility to HIV infection and progression of AIDS in relation to variant
      alleles of mannose-binding lectin.
AB  - BACKGROUND: Low serum concentrations of mannose-binding lectin (MBL) are
      associated with increased susceptibility to recurrent infection. Three variant
      alleles in the MBL gene (B, C, and D), cause low serum concentrations of the
      protein. We investigated whether variant alleles of MBL affect susceptibility to
      infection with HIV and progression of AIDS. METHODS: Between 1983 and 1986, all
      men who attended two clinics in Copenhagen for HIV screening were invited to take
      part in our study. We investigated the prevalence of variant alleles of MBL
      (detected by PCR) and assessed the prognostic value of these alleles and the
      corresponding serum MBL concentrations (measured by ELISA) in 96 homosexual men
      with HIV infection and in two control groups (123 healthy adults and 36 HIV
      negative homosexual men at high risk of HIV infection because of their sexual
      behaviour). Follow-up was for up to 10 years. FINDINGS: Eight (8%) of the HIV
      infected men were homozygous for the variant MBL alleles compared with one (0.8%)
      of the healthy controls (p = 0.005) and none of the high-risk homosexual controls
      (p = 0.05). We found no significant association between MBL genotype and time
      from first positive HIV test to progression of AIDS (p = 0.8). However, in the 61
      HIV-infected men who developed AIDS, the median survival time was significantly
      shorter after the AIDS diagnosis for men who were carriers of the variant alleles
      (both homozygous and heterozygous) than for men homozygous for the normal MBL
      allele (11 [IQR 4-21] vs 18 months [9-44], p = 0.007). Among men who developed
      AIDS, there was a significant difference in survival time between those with
      serum MBL concentrations below the lower quartile, those within the IQR, and
      those above the upper quartile (p = 0.02). Multivariate analysis showed that men
      who developed AIDS and had low serum MBL concentrations had an increased rate of
      rapid death, independently of CD4 T-cell counts at AIDS diagnosis.
      INTERPRETATION: Our findings suggest that homozygous carriers of variant MBL
      alleles are at increased risk of HIV infection, either directly or indirectly
      because of increased susceptibility to coinfections. These alleles are also
      associated with a significantly shorter survival time after a diagnosis of AIDS.

PMID- 9014911
TI  - Herpes simplex virus type 1 in brain and risk of Alzheimer's disease.
AB  - BACKGROUND: The apolipoprotein E epsilon 4 (APOE-epsilon 4) allele is a risk
      factor for Alzheimer's disease (AD), but it is neither essential nor sufficient
      for development of the disease. Other factors-genetic or environmental-must
      therefore have a role. By means of a PCR we have detected herpes simplex virus
      type 1 (HSV1) in latent form in brains of elderly people with and without AD. We
      have postulated that limited reactivation of the virus causes more damage in AD
      patients than in elderly people without AD because of a difference in the hosts.
      We now report the APOE genotypes of AD patients and non-AD sufferers with and
      without HSV1 in brain. METHODS: DNA was extracted from 84 samples of brain from
      46 AD patients (39 temporal lobe, 39 frontal lobe, three hippocampus) and from 75
      samples of brain from 44 non-AD elderly people (33 temporal lobe, 36 frontal
      lobe, six hippocampus). PCR amplification was used to detect HSV1 thymidine
      kinase gene and the host APOE gene. FINDINGS: By multiple logistic regression,
      the APOE-epsilon 4 allele frequency was significantly higher in the patients
      positive for HSV1 in brain than in the HSV1-negative AD group, the HSV1-positive
      non-AD group, or the HSV1-negative non-AD group (52.8% vs 10.0%, 3.6%, and 6.3%,
      respectively). The odds ratio for APOE-epsilon 4 in the HSV1-positive AD group
      compared with HSV1-negative non-AD group was 16.8 (95% CI 3.61-77.8) and in the
      HSV1-negative AD group, 1.67 (0.21-13.4). We also compared APOE genotypes of 40
      people who had recurrent cold sores and 33 non-sufferers; the APOE-epsilon 4
      allele frequencies were 36% and 9%, respectively (p < 0.0001). INTERPRETATION:
      These findings suggest that the combination of HSV1 in brain and carriage of an
      APOE-epsilon 4 allele is a strong risk factor for AD, whereas either of these
      features alone does not increase the risk of AD. The findings in people with cold
      sores support our hypothesis that APOE-epsilon 4 and HSV1 together are damaging
      in the nervous system.

PMID- 9014912
TI  - Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid
      haemorrhage.
AB  - BACKGROUND: Subarachnoid haemorrhage is commonly associated with natriuresis and
      hyponatraemia. One possible explanation for these features is a defect in the
      central regulation of renal sodium reabsorption with increased secretion of a
      natriuretic factor. We investigated whether excess sodium secretion in patients
      with subarachnoid haemorrhage is related to increased secretion of natriuretic
      peptides or to the presence of digoxin-like immunoreactive substances. METHODS:
      We measured the plasma concentrations of digoxin-like immunoreactive substances
      (by a fluorescence polarisation immunoassay) and natriuretic peptides,
      aldosterone, renin, and antidiuretic hormone (by radioimmunoassay) in ten
      patients with aneurysmal subarachnoid haemorrhage, ten patients undergoing
      elective craniotomy for cerebral tumours, and 40 healthy controls of similar age
      and sex distribution. Samples were collected before surgery, 1 h, 4 h, and 12 h
      after surgery, then daily until 7 days postoperatively in the two groups of
      patients. FINDINGS: All patients with subarachnoid haemorrhage, but none of the
      tumour patients, showed increased urine output and urinary excretion of sodium (p
      = 0.018 for comparison of means of curves to 7 days). The patients with
      subarachnoid haemorrhage had much higher plasma concentrations of brain
      natriuretic peptide (BNP) than controls, on admission (mean 15.1 [SE 3.8] vs 1.6
      [1.0] pmol/L, p < 0.001) and throughout the study period, accompanied by lower
      than normal aldosterone concentrations and normal plasma concentrations of atrial
      and C-type natriuretic peptides (ANP, CNP). The patients with tumours had similar
      plasma concentrations of ANP, BNP, and CNP to the controls. We did not detect
      digoxin-like immunoreactive substances in either group of patients.
      INTERPRETATION: Salt-wasting of central origin may induce hyponatraemia in
      patients with aneurysmal subarachnoid haemorrhage, possibly as a result of
      increased secretion of BNP with subsequent suppression of aldosterone synthesis.

PMID- 9014913
TI  - Viper's blood and bile.

PMID- 9014914
TI  - Gastric volvulus after coronary bypass.

PMID- 9014915
TI  - Respiratory failure due to insufflated talc.

PMID- 9014916
TI  - Botulinum toxin for palmar hyperhidrosis.

PMID- 9014917
TI  - Treatment of vaginismus with botulinum toxin injections.

PMID- 9014918
TI  - Effect of diagnosis of "smoker's lung". RYLUNG Group.

PMID- 9014919
TI  - Treatment of systemic sclerosis with autologous haemopoietic stem cell
      transplantation.

PMID- 9014920
TI  - Leptospirosis presenting as haemorrhagic fever in visitor to Africa.

PMID- 9014921
TI  - Circulating spindle cells: correlation with human herpesvirus-8 (HHV-8) infection
      and Kaposi's sarcoma.

PMID- 9014922
TI  - Efficacy of low-dose halofantrine for second treatment of uncomplicated
      falciparum malaria.

PMID- 9014923
TI  - Intestinal capillariasis in neolithic inhabitants of Chalain (Jura, France)

PMID- 9014924
TI  - US expert panel reaffirms benefit of perinatal zidovudine.

PMID- 9014925
TI  - Oral HIV test found to be highly accurate.

PMID- 9014926
TI  - Helicobacter pylori infection.

PMID- 9014928
TI  - Literature and medicine: physician-poets.

PMID- 9014927
TI  - The treatment of acute leukaemia.
AB  - Developments in supportive care, new regimens for induction of remission and
      consolidation therapy, and bone-marrow transplantation have improved the outlook
      for patients with acute leukaemia. The outlook, though, is influenced by age and
      factors related to the biology of the disease. In acute myeloid leukaemia age is
      such an important factor that it determines approach to therapy. Overcoming
      resistance to chemotherapy is an area that needs much attention.

PMID- 9014929
TI  - Is habitual caffeine use a preventable cardiovascular risk factor?

PMID- 9014930
TI  - Magnesium in acute myocardial infarction.

PMID- 9014931
TI  - Magnesium in acute myocardial infarction.

PMID- 9014932
TI  - Life expectancies in children with cerebral palsy.

PMID- 9014933
TI  - Life expectancies in children with cerebral palsy.

PMID- 9014934
TI  - Analysis of IVF data.

PMID- 9014935
TI  - Insulin resistance syndrome and childhood social conditions.

PMID- 9014936
TI  - Early cirrhosis--or primary cholangitis?

PMID- 9014937
TI  - Smoking cessation in comprehensive pulmonary rehabilitation.

PMID- 9014938
TI  - Fetal growth and coronary heart disease.

PMID- 9014939
TI  - Fetal growth and coronary heart disease.

PMID- 9014940
TI  - Fetal growth and coronary heart disease.

PMID- 9014941
TI  - Use of reagent strips to diagnose bacterial meningitis.

PMID- 9014942
TI  - Patent foramen ovale and decompression illness in divers.

PMID- 9014943
TI  - Patent foramen ovale and decompression illness in divers.

PMID- 9014944
TI  - Counselling parents of extremely premature babies.

PMID- 9014945
TI  - Classification of folic acid.

PMID- 9014946
TI  - Clinical cancer trials in developing countries.

PMID- 9014947
TI  - The successful introduction of general anaesthesia.

PMID- 9014948
TI  - Dynamic study of iodized oil in the liver and blood supply to hepatic tumors. An
      experimental investigation in several animal species.
AB  - A better understanding of the biologic behavior of embolic agents in the liver
      and the blood supply to hepatic tumors is of utmost importance in embolization
      and chemoembolization. In vivo microscopy, which allows observation of live
      hepatic circulation, was used in this study along with angiography, vascular cast
      technique, and light and electron microscopy. Iodized oil injected into the
      hepatic artery passed through the peribiliary plexus to enter the portal vein,
      and subsequently traversed the hepatic sinusoids. The time required for clearance
      of the oil from the liver and recovery of the microcirculation depended largely
      on the patency of the hepatic artery. Kupffer cells actively captured and
      phagocytosed iodized oil droplets in hepatic sinusoids. The hepatic tumors were
      confirmed to have a dual blood supply from the hepatic artery and the portal
      vein. Embolization of either the hepatic artery or the portal vein alone did not
      completely stop the blood circulation in the tumors. A reciprocal relationship
      between the hepatic artery and the portal vein in the blood supply to hepatic
      tumors was demonstrated dynamically and intrahepatic arterioloportal
      communications, especially the peribiliary plexus, play an important role in the
      tumor circulation. The current trans-catheter intraarterial management of hepatic
      tumors is insufficient in that it deals only with the hepatic arterial blood
      supply and ignores that from the portal vein. Iodized oil creates the potential
      for dual embolization of the hepatic tumor through a single hepatic arterial
      catheterization.

PMID- 9014949
TI  - Clinical implications of maximal respiratory pressure determinations for
      individuals with Duchenne muscular dystrophy.
AB  - OBJECTIVE: To analyze the relationship between disease progression, pulmonary
      volumes, respiratory muscle strength (maximum inspiratory [MIP] and expiratory
      [MEP] pressure), and arterial blood gases for patients with Duchenne muscular
      dystrophy (DMD). DESIGN: An inception cohort study of pulmonary volumes, MIPs,
      and MEPs, correlated with age and PaCO2 levels and with each other using linear
      and nonlinear regression analyses. SETTING: Outpatient clinic. PATIENTS: Fifty
      two consecutive DMD patients who presented for regular evaluations at a regional
      DMD center. RESULTS: Maximum expiratory pressures were 47.7% +/- 10.9% of normal
      in the 167- to 14-year-old patients and decreased linearly thereafter (MEP% = 
      2.7 x age +73.8; p < .001). Declines in MEP also correlated linearly with
      expiratory reserve volume (p < .001) and inversely with residual volume (p <
      .001). By contrast, MIP was 66.3% +/- 19.0% in the 357- to 14-year-old patients
      and then declined to 30.2% +/- 19.5% after age 14. No linear relationships were
      found with age but declines did correlate linearly with inspiratory reserve
      volume (p < .001) and total lung capacity (p < .001). PaCO2 elevations correlated
      best with decreases in MIP (p < .0001) and appeared when MIP was below 30cmH2O.
      CONCLUSIONS: Lung volume changes in DMD patients correlate with respiratory
      muscle weakness, and although inspiratory muscle dysfunction plays a key role in
      the development of chronic ventilatory insufficiency, reductions in expiratory
      muscle strength are the first signs of dysfunction and lead to the first episodes
      of respiratory failure.

PMID- 9014950
TI  - Attentional deficits in stroke patients: a visual dual task experiment.
AB  - OBJECTIVE: (1) To compare the performance of subjects who have suffered a single
      lateralized cortical, ischemic stroke versus controls on measures of attention
      including a computerized dual visual attentional task to determine if this task
      is more sensitive for detecting the presence of subtle hemi-inattention compared
      to traditional attention tasks; (2) to determine if there is evidence of hemi
      inattention in persons who completed spontaneous neurological recovery after a
      cortical, ischemic stroke compared to controls. SUBJECTS: Thirty-six patients (N
      = 20 Right Hemisphere and N = 16 Left Hemisphere) who had previously undergone
      stroke rehabilitation and who were at least 1 year poststroke. All patients were
      currently living in the community. A control group of 20 subjects was recruited
      from the community. RESULTS: There was no difference in performance between the
      three groups on gross clinical testing for hemi-inattention, or on the
      traditional letter-cancellation tasks. All subjects also participated in two
      computer generated tasks: (1) tracking a moving stimulus and (2) detecting
      briefly appearing targets. On the single task performance the control group
      performed significantly better than both cerebrovascular accident (CVA) groups (p
      < .004), but with no trend for hemi-inattention in any individual group. When the
      two computer tasks were combined, there was a significant difference in
      performance between the control group and all stroke subjects (p < .02) for
      target detection. A fatiguing effect over time was also found in the right CVA
      group on the dual task. Stroke subjects driving at the time of data collection
      performed better on the dual attentional task compared to stroke subjects not
      driving (p = .05). CONCLUSIONS: On single and dual dynamic computerized visual
      attentional tasks, individuals who have suffered a cortical stroke more than 1
      year before testing have significantly impaired attention compared to controls.

PMID- 9014951
TI  - Disuse muscle atrophy of lower limbs in hemiplegic patients.
AB  - OBJECTIVE: To clarify the histopathologic findings from lower limb muscles in
      hemiplegic patients and determine whether the findings are related to the
      severity of paralysis or daily physical activity. DESIGN: Nonrandomized control
      trial. SETTING: Referral center. PATIENTS: Eight patients were selected from 21
      hemiplegic persons who underwent a muscle biopsy, and the controls were four men
      who had no abnormal findings in their histopathology. MAIN OUTCOME MEASURES:
      Morphometric evaluations of bilateral vastus lateralis muscles on the involved (I
      VL) and non-involved (N-VL) sides in eight hemiplegic subjects, five flexor
      hallucis longus muscles on the involved side (I-FHL), and vastus lateralis
      muscles of four controls (C-VL) were performed. Muscle fiber diameters were
      measured with an image analyzer, and atrophy factors, hypertrophy factors, and
      fiber type proportions were calculated based on the data. RESULTS: The
      morphometric measurements revealed that the hemiplegic patients had type 2 fiber
      atrophy, type 2B fiber atrophy, and type 2 fiber atrophy with type 1 fiber
      hypertrophy in the I-VL, N-VL, and I-FHL, respectively, and that the controls had
      no muscle fiber atrophy or hypertrophy. The muscle fiber atrophy in the
      hemiplegic patients was not related to the period after the onset, the severity
      of paralysis, or activities of daily living score but was related to daily
      physical activity. CONCLUSIONS: Although the hemiplegic patients had undergone
      rehabilitative treatments, which did not include muscle strengthening exercises,
      in a hospital without a board-certified doctor of rehabilitation medicine, a
      considerable amount of muscle atrophy was found characteristic of changes seen in
      disuse.

PMID- 9014952
TI  - Influence of simulated bed rest and intermittent weight bearing on single
      skeletal muscle fiber function in aged rats.
AB  - OBJECTIVE: To characterize specific musculoskeletal contractile property changes
      that occur during inactivity and intermittent weight bearing in aged muscle.
      DESIGN: Randomized control trial. SETTING: A controlled laboratory environment.
      SUBJECTS: Fifteen aged rats were randomly assigned to control (CON), hindlimb
      unweighted (HU), and hindlimb unweighted with intermittent weight bearing (HU
      IWB) groups. INTERVENTIONS: The HU and HU-IWB rats were suspended for 1 week. The
      HU-IWB animals were unsuspended four times daily allowing 15 minutes of weight
      bearing. MAIN OUTCOME MEASURES: Muscle weights, muscle fiber diameter, peak
      absolute force, peak specific tension (P0), and maximal shortening velocity (V0).
      RESULTS: In comparison to CON animals, the soleus (SOL) wet weight was
      significantly (p < or = .05) reduced by 19% and 6% in HU and HU-IWB animals,
      respectively. SOL single fiber analysis showed no difference in fiber diameter
      between the three groups. However, peak absolute force and P0 of SOL type I
      fibers were significantly (p < or = .05) reduced in the HU group compared to CON
      values. V0 of SOL fibers increased with HU. In comparison to CON animals, the
      gastrocnemius (GAS) wet weight was significantly reduced by 9% and 8% in HU and
      HU-IWB animals, respectively. CONCLUSIONS: Inactivity significantly altered the
      contractile properties of single fibers isolated from aged mammalian SOL skeletal
      muscle. Furthermore, minimal weight bearing attenuated these detrimental effects
      induced by inactivity in the SOL. However, this weight-bearing protocol did not
      attenuate the inactivity-induced alterations in aged mammalian GAS skeletal
      muscle.

PMID- 9014953
TI  - Reference values for extremity muscle strength obtained by hand-held dynamometry
      from adults aged 20 to 79 years.
AB  - OBJECTIVE AND DESIGN: Only a few studies have provided reference values for
      muscle strength obtained by hand-held dynamometry. Such values are essential for
      establishing the degree to which an individual's strength is impaired. This
      descriptive study was conducted to provide reference values for the strength of
      10 extremity muscle actions. SUBJECTS AND INSTRUMENTATION: A convenience sample
      of 106 men and 125 women volunteers was tested twice with an Ametek digital hand
      held dynamometer. RESULTS: The measurements were found to be reliable. Predictive
      equations are provided for the measurements. Reference values generated are
      expressed in Newtons and as a percentage of body weight and are organized by
      gender, decade of age, and side. CONCLUSIONS: The values can be employed in a
      clinical setting to document whether an individual is impaired relative to
      healthy subjects of the same gender and age.

PMID- 9014954
TI  - Long-term psychological outcomes in spinal cord injured persons: results of a
      controlled trial using cognitive behavior therapy.
AB  - OBJECTIVE: Although there are many anecdotal reports that psychological
      intervention is effective in enhancing adjustment to spinal cord injury (SCI),
      there are little data to support this assertion. To date, reports of few
      longitudinal-based controlled trials that assessed psychological outcomes for SCI
      persons have been published. This study was conducted to determine long-term
      efficacy of cognitive behavior therapy during rehabilitation. DESIGN: The study
      employed a nonrandomized controlled trial, and measures were taken on three
      occasions: before, immediately after, and 12 months after treatment. SETTING,
      OUTCOME MEASURES, AND INTERVENTION: Anxiety, depressive mood, and self-esteem
      were assessed in 28 SCI persons consecutively selected on admission to hospital,
      who participated in specialized group cognitive behavior therapy (CBT) during
      rehabilitation. CONTROLS: The intervention group's responses on the measures were
      compared with a control group of 41 SCI persons who only received traditional
      rehabilitation services during their hospitalization. RESULTS: There were no
      overall group differences on anxiety, depressive mood, and self-esteem, although
      there was a trend for the treatment group to have greater levels of improvement
      in depression scores across time in comparison to the control group. However,
      those in the treatment group who reported high levels of depressive mood before
      the CBT treatment were significantly less depressed 1 year after injury, compared
      to similar persons in the control group. CONCLUSIONS: While it appears not
      everyone who experiences SCI needs CBT, at least in the hospital phase of their
      rehabilitation, those who report high levels of depressive mood benefited greatly
      from CBT.

PMID- 9014955
TI  - Ambulatory capacity in spinal cord injury: significance of somatosensory evoked
      potentials and ASIA protocol in predicting outcome.
AB  - OBJECTIVE: Prediction of outcome of ambulatory capacity in patients with acute
      spinal cord injury (SCI) by the American Spinal Injury Association (ASIA)
      protocol and somatosensory evoked potentials (SSEP). DESIGN: Correlational study
      on a prospective cohort. SETTING: Spinal cord injury center, university hospital.
      PATIENTS: Consecutively sampled, 70 acute and 34 chronic SCI patients. MAIN
      OUTCOME MEASURES: (1) ASIA motor and sensory scores; (2) tibial and pudendal SSEP
      graded in 5 categories, from normal to absent; (3) ambulatory capacity rated as
      no, therapeutic, functional, or full. The outcome of the ambulatory capacity was
      assessed after discharge from the rehabilitation program, at least 6 months after
      trauma. RESULTS: In acute SCI both the initial ASIA scores and the SSEP
      recordings are related (p < .001) to the outcome of ambulatory capacity. In acute
      tetraplegia the pudendal SSEP (spearman corr. coeff. .92; p < .001) and in acute
      paraplegia the ASIA motor score (spearman corr. coeff. .90; p < .001) were best
      related to the outcome of ambulatory capacity. In the early stage of acute SCI,
      ASIA scores and SSEP recordings can help to assess the outcome of ambulatory
      capacity and, therefore, can contribute to the selection of the appropriate
      therapeutic approaches during the rehabilitation program. In patients with acute
      SCI the ASIA motor score significantly increased (p < .05) in the 6 months after
      trauma, whereas the ASIA sensory scores and SSEP recordings did not change
      significantly during this same period. CONCLUSION: ASIA scores and SSEP are
      related to the outcome of ambulatory capacity in patients with acute spinal cord
      injury; in noncomprehensive or uncooperative patients the SSEP are of
      supplemental value to the clinical examination. Therefore, the combination of
      clinical and electrophysiological examinations can be of additional diagnostic
      value in the assessment of acute spinal cord injury.

PMID- 9014956
TI  - Circulating levels of IL-2R, ICAM-1, and IL-6 in spinal cord injuries.
AB  - OBJECTIVE: To measure circulating levels of well-studied, easily quantifiable
      surrogate markers or mediators of inflammation and tissue remodeling in patients
      with spinal cord injury (SCI) suffering from pressure ulcers. Cytokines or their
      receptors, eg, interleukins IL-6 and IL-2, IL-2R (the soluble interleukin-2
      receptor), and the intercellular adhesion molecule ICAM-1, are mediators of
      immune response, inflammatory processes, and tissue remodeling involving the skin
      and other organs. Activation of these immune effectors and their accumulation in
      tissue can be associated with pathological changes or healing, and elevated
      plasma concentrations can indirectly reflect the magnitude of immune activation.
      DESIGN: Participants were consecutively enrolled in a controlled, gender-specific
      study of the relationship between circulating IL-1 beta, IL-2, IL-2R, and ICAM-1
      and pressure ulcers in patients with chronic SCI. SETTING: The department of
      medicine of a university-affiliated medical center and the spinal cord injury
      service at a Department of Veterans Affairs medical center. PATIENTS OR OTHER
      PARTICIPANTS: Seventy men with longstanding SCI (19 with pressure ulcers). The
      mean age was 49 +/- 14 (range 25 to 74 years). Duration of SCI ranged between 1
      and 46 years, and the level of injury varied from C2 to L5. The control group
      consisted of 20 healthy, able-bodied volunteers (10 men and 10 women aged 25 to
      50 years). MAIN OUTCOME MEASURES: Circulating plasma levels of IL-6, IL-2, IL-2R,
      and ICAM-1 and their relation to the rate of wound healing in subjects with SCI.
      RESULTS: Plasma concentrations of bioactive molecules IL-6, IL-2R, and ICAM-1
      were numerically or significantly elevated in all patients with SCI as compared
      to able-bodied individuals. The greatest increase in concentration was seen in
      those patients with pressure ulcers who demonstrated slow healing of their
      wounds. CONCLUSIONS: SCI and trauma to insensitive tissue result in
      immunoactivation. In patients with SCI and pressure ulcers, elevated levels of
      circulating ICAM-1 and IL-2R may have diagnostic, prognostic, and therapeutic
      value in predicting or differentiating subgroups of patients who will vary in the
      severity or the rate of healing of their wounds.

PMID- 9014957
TI  - Predicting patient scores between the functional independence measure and the
      minimum data set: development and performance of a FIM-MDS "crosswalk".
AB  - OBJECTIVE: The functional status of rehabilitation patients is often measured
      using the Functional Independence Measure (FIM) in acute rehabilitation settings
      or the Minimum Data Set (MDS) in nursing homes. Because the relationship between
      the two instruments is unknown, preventing comparison of rehabilitation patients
      in different types of settings, a translation formula ("crosswalk") between items
      and subscales from the FIM and the MDS was developed and tested. DESIGN AND
      OUTCOME MEASURES: Using definitions recommended by an expert panel, MDS items
      were chosen and rescaled (termed "Pseudo-FIM(E)" items) to correspond to FIM
      items. The empiric relationships between Pseudo-FIM(E) and FIM scores were then
      measured using paired FIM-MDS assessments. SETTING AND PATIENTS: 173
      rehabilitation patients admitted to six nursing homes. RESULTS: Pseudo-FIM(E)
      items could be defined for 12 of the 18 FIM items (8 motor and 4 cognitive
      items). Mean FIM and Pseudo-FIM(E) scores were not significantly different (p >
      .30) for 5 of the 12 items. Mean scores for the remaining 7 items and for motor
      and cognitive subscales were similar but statistically significantly different (p
      < .05). Intraclass correlation coefficients between the FIM and Pseudo-FIM(E)
      motor and cognitive subscales were both .81. CONCLUSIONS: FIM and MDS items can
      be used to predict item and subscale scores between the two instruments with
      reasonable accuracy. This capability will enhance efforts to compare case-mix
      between acute rehabilitation and nursing home rehabilitation patients, thus
      making feasible comparisons of the effectiveness (degree of improvement among
      similar patients) and efficiency (cost of care to obtain a given degree of
      improvement) of rehabilitation care in different types of settings.

PMID- 9014958
TI  - Combined neuromuscular electrical stimulation and transcutaneous electrical nerve
      stimulation for treatment of chronic back pain: a double-blind, repeated measures
      comparison.
AB  - OBJECTIVES: A preliminary examination of NMES and combined NMES/TENS for the
      management of chronic back pain. DESIGN: Double-blind, placebo-controlled,
      randomized repeated measures. SUBJECTS AND SETTING: Consecutive sample of 24
      chronic back pain patients (16 women and 8 men) attending an outpatient pain
      clinic (mean age 51.67 years, mean pain duration 3.83 years). All treatments were
      administered at home. INTERVENTIONS: Subjects self-administered NMES, combined
      NMES/TENS, TENS, and placebo treatments. Each treatment had a duration of 5
      consecutive hours per day over 2 consecutive days, with a 2-day hiatus between
      treatments to minimize carryover effects. MAIN OUTCOME MEASURES: Pain reduction
      was assessed through pretreatment to posttreatment differences on the Present
      Pain Intensity (PPI) scale, and a visual analogue scale of Pain Intensity (VAS
      I). Posttreatment pain relief was assessed using a visual analogue scale of Pain
      Relief (VAS-R). RESULTS: Combined treatment, NMES, and TENS each produced
      significant pretreatment to posttreatment reductions in pain intensity as
      measured by both the PPI and VAS-I (p < .05). Combined treatment was superior to
      placebo on pain reduction (p = .001, p = .016) as well as pain relief (p < .001).
      Combined treatment was also superior to both TENS and NMES for pain reduction and
      pain relief (p < .01). NMES and TENS were superior only to placebo for pain
      relief (p < .001). CONCLUSIONS: Combined NMES/TENS treatment consistently
      produced greater pain reduction and pain relief than placebo, TENS, or NMES. NMES
      alone, although less effective, did produce as much pain relief as TENS. Although
      preliminary, this pattern of results suggests that combined NMES/TENS may be a
      valuable adjunct in the management of chronic back pain. Further research
      investigating the effectiveness of both NMES and combined NMES/TENS seems
      warranted.

PMID- 9014959
TI  - Caffeine and chronic back pain.
AB  - OBJECTIVE: Tobacco use and other behavioral factors are associated with chronic
      back pain. Anecdotes suggest excess caffeine use may also be associated with
      chronic back pain. We compared caffeine consumption by chronic back pain patients
      with caffeine consumption by controls. DESIGN: Retrospective case-control study.
      SETTING: A multispecialty outpatient facility. PATIENTS: Sixty new, consecutive
      patients with chronic back pain compared to 60 new, consecutive patients without
      chronic back pain. INTERVENTION: Patients were prospectively asked to complete an
      intake questionnaire. MAIN OUTCOME MEASURE: Daily caffeine consumption was
      estimated by analyzing the intake questionnaire. Differences between groups were
      analyzed by both normal and nonparametric statistics. RESULTS: Consumption of
      caffeine by patients with chronic back pain averaged 392.4 mg/day. Controls
      consumed 149.8 mg/ day, a significant difference (p = .0001). Men consumed 86%
      more caffeine per day than women (p = .02). Age and caffeine consumption showed
      little correlation (r = .126). CONCLUSIONS: Patients with chronic back pain
      consume over twice as much caffeine as patients without chronic back pain.
      Confounding variables and possible mechanisms associating caffeine with chronic
      back pain are discussed.

PMID- 9014961
TI  - Exercise training improves functional recovery and motor nerve conduction
      velocity after sciatic nerve crush lesion in the rat.
AB  - OBJECTIVE: To observe the effects of exercise training on recuperation of
      sensorimotor function in the early phase of regeneration, and to monitor the long
      term effects of exercise on electrophysiological aspects of the regenerating
      nerve. DESIGN: After sciatic nerve crush in 20 male Wistar rats, one random
      selected group was subjected to 24 days of exercise training, whereas the other
      group served as sedentary controls. INTERVENTIONS: Exercise training was induced
      for 24 days, starting the first postoperation day, by placing bottles of water at
      such a height that the exercising rats had to maximally erect on both hindpaws to
      drink. MAIN OUTCOME MEASURES: Recovery of motor and sensory function in the early
      phase was monitored by analysis of the free walking pattern and the foot reflex
      withdrawal test, respectively. Electrophysiological measurements on postoperation
      days 50, 75, 100, 125, and 150 were used to evaluate the late phase of recovery
      of nerve conduction velocity. RESULTS: During the early phase of the recovery
      period, exercise training enhanced functional recovery. The motor nerve
      conduction velocity (MNCV), as measured in the late phase of recovery, was
      significantly better in the trained group than in the control group (p < .01).
      CONCLUSIONS: We conclude that exercise training enhances the return of
      sensomotoric function in the early phase of recovery from peripheral nerve
      lesion. Furthermore, these results suggest that the beneficial effects of 24 days
      of exercise training after crush persist in the late phase of peripheral nerve
      recovery.

PMID- 9014960
TI  - Isometric torso rotation strength: effect of training frequency on its
      development.
AB  - OBJECTIVE: To examine training frequency's effect on torso rotation muscle
      strength. DESIGN: The study followed a pretest-posttest randomized-group design.
      SETTING: University laboratory. PATIENTS: Subjects, 33 men (age 30 +/- 11yr) and
      25 women (age 28 +/- 10yr) with no history of low back pain, volunteered to
      participate in the study and were tested for isometric (IM) torso rotation
      strength before (T1) and after (T2) 12 weeks of training. Measurements of maximal
      voluntary IM torso rotation torque (N.m) were made through a 108 degrees range of
      motion (54 degrees, 36 degrees, 18 degrees, 0 degree, -18 degrees, -36 degrees, 
      54 degrees). Subjects were stratified by peak torque at T1, and randomized to a
      nonexercising control group (C, n = 10), or groups that trained once a week
      (1x/wk, n = 16), twice a week (2x/wk, n = 17), or three times a week (3x/wk, n =
      15); and all groups were similar in strength. INTERVENTIONS: Training consisted
      of 8 to 12 repetitions of full range dynamic variable resistance exercise to
      volitional fatigue, for both left and right rotation. MAIN OUTCOME: To determine
      the best training frequency for the development of torso rotation strength.
      RESULTS: Relative improvements (average increase in strength gained at each
      angle) for the training groups were 4.9%, 16.3%, and 11.9% for the 1, 2, and
      3x/wk groups, respectively. The 1x/wk group did not increase in IM torso rotation
      strength compared to the control group at any angle. Both the 2 and 3x/ wk groups
      increased their IM torso rotation strength compared to the control group at all
      but one angle. There were no significant differences in IM torso rotation
      strength between the groups that trained 2 or 3x/wk. During the training period,
      the 2 and 3x/wk groups increased their dynamic training load significantly more
      than the 1x/wk group. CONCLUSIONS: Posttraining dynamic strength was not
      different between training frequencies of 2 and 3x/wk. Therefore, training the
      rotary torso muscles 2x/wk is recommended.

PMID- 9014962
TI  - Effects of rear-wheel camber on wheelchair stability.
AB  - OBJECTIVES: To evaluate how using a wheelchair with rear-wheel camber (when the
      bottoms of the wheels are farther apart than the tops) is associated with the
      risk of instability incidents, and to determine the effect of camber on
      wheelchair stability. DESIGN, SETTING, PATIENTS: Epidemiologic data were analyzed
      from a sample of 576 users of manually propelled wheelchairs in Nova Scotia. A
      controlled trial was performed using a representative wheelchair occupied by an
      anthropomorphic test dummy, altering the camber in 5 degrees increments from -15
      degrees to +15 degrees. MAIN OUTCOME MEASURES: For the epidemiologic study,
      univariate and multivariate analyses were used. To measure the static stability,
      a tilting platform was used according to the guidelines of the International
      Organization for Standardization. RESULTS: Camber users reported significantly
      more instability incidents; of these incidents, more were in the rear direction
      (40% vs 27%) and fewer in the lateral direction (17% vs 28%) (p < .01). When
      controlling for other factors, camber was associated with a 3.91-fold increased
      risk of sustaining an instability incident (p < .001). With increases in camber
      angle in the laboratory, lateral and forward stability increased and rear
      stability decreased (with the wheels unlocked and locked) (p < .001). CONCLUSION:
      Camber use is negatively associated with instability incidents in the lateral
      direction and positively associated with incidents in the backward direction,
      probably due in part to the effects of camber on lateral and rear stability.

PMID- 9014963
TI  - Shoehorn-type ankle-foot orthoses: prediction of flexibility.
AB  - OBJECTIVE: To predict the factors affecting the flexibility of a shoehorn-type
      ankle-foot orthosis (AFO) in dorsiflexion and plantarflexion. DESIGN:
      Experimental assessment. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The
      dorsiflexion and plantarflexion angles of the ankle joints of the AFOs versus
      applied force were measured. RESULTS: The dorsiflexion and plantarflexion angles
      demonstrated significant negative linear correlations with the height of the AFO
      (p < .01), the height of the medial wall (p < .05), the height of the lateral
      wall (p < .01), the width of the narrowest area (p < .001), and the width of the
      ankle joint area (p < .001). The dorsiflexion angle also demonstrated a
      significant negative linear correlation with the curvature radius of the lateral
      trimline (p < .05) and the thickness of the plastic sheet (p < .05). Stepwise
      multiple regression analysis demonstrated that the width of the ankle joint area,
      the thickness of plastic sheet, and the height of the lateral wall significantly
      affected the dorsiflexion and plantarflexion angles (p < .001). CONCLUSION: The
      major predictor of flexibility in dorsiflexion and plantarflexion is the width of
      the ankle joint area, and the second predictor is the thickness of the plastic
      sheet in dorsiflexion and the height of the lateral wall in plantarflexion.

PMID- 9014964
TI  - Intraoperative monitoring of skin temperature changes of hands before, during,
      and after endoscopic thoracic sympathectomy: using infrared thermograph and
      thermometer for measurement.
AB  - OBJECTIVE: To investigate the roles of the second and third thoracic spinal
      segments in the preganglionic sympathetic innervation of the hand, and to compare
      skin temperature changes between thenar and other parts of palm before, during,
      and after endoscopic thoracic sympathectomy. DESIGN: Twelve patients, four women
      and eight men, with severe palmar hyperhydrosis underwent endoscopic thoracic
      sympathectomy. The T3 segment was identified and dissected first, followed by T2
      segment extirpation. Skin temperature changes of the hand were assessed by
      thermograph and thermometer simultaneously before, during, and after
      sympathectomy. Sympathetic skin responses were undertaken 1 day preoperatively
      and followed up 6 months postoperatively. SETTING: An electrophysiological
      laboratory and operating room in a national medical center. SUBJECTS: Twelve
      patients who sustained a profound degree of palmar hyperhydrosis. INTERVENTIONS:
      Skin temperature differences of the hands were measured by infrared thermograph
      and thermometer before, during, and after endoscopic thoracic sympathectomy. MAIN
      OUTCOME MEASURES: Group's average temperature differences, and sympathetic skin
      response (all or none response). RESULTS: The T2 spinal segment is thought to be
      the main source of sympathetic outflow to the sweat glands of the hand. The
      group's average temperature changes were significantly higher at the 2nd through
      5th fingers' tips than at the thenar after completion of T2 extirpation (p <
      .005). CONCLUSIONS: Intraoperative monitoring of palmar skin temperature, as
      judiciously measured by infrared thermograph, yields useful information about the
      locations of the sympathetic segments and confirmation of their entire ablation
      by endoscopic thoracic sympathectomy.

PMID- 9014965
TI  - Rehabilitative management of polyarteritis: a case report.
AB  - A 75-year-old woman with polyarteritis who developed polyneuropathy and
      quadriplegia underwent intensive rehabilitation that resulted in significant
      improvement. This report discusses various therapeutic strategies for the
      successful management of patients with severe polyarteritis. Strategies include
      orthotics for both upper and lower extremities, sensory reeducation, edema
      management, and the use of adaptive devices in retraining the patient with
      activities of daily living. The associated neurological, orthopedic, renal, and
      cardiac complications in the context of rehabilitation for this complex condition
      are discussed.

PMID- 9014966
TI  - Simultaneous bilateral thalamic hemorrhages following the administration of
      intravenous tissue plasminogen activator.
AB  - A patient suffered the onset of simultaneous bilateral thalamic hemorrhage
      several hours after the administration of intravenous tissue plasminogen
      activator. The patient exhibited features of the paramedian diencephalic
      syndrome, including executive dysfunction, anterograde amnesia, inattention, and
      disturbances of visual perception. During rehabilitation, she made significant
      gains in overlearned activities of daily living tasks, but her inability to
      retain new information left her severely disabled. The use of intravenous
      thrombolytic therapy is believed to account for this patient's unusual stroke
      syndrome. With recent evidence supporting the efficacy of intravenous
      thrombolysis in acute stroke, patients with multiple hemorrhagic strokes as a
      result of thrombolysis may become more common on rehabilitation services.

PMID- 9014967
TI  - Tension myalgia versus myoadenylate deaminase deficiency: a case report.
AB  - Myalgia is a complaint associated with numerous medical conditions such as
      metabolic or hormonal abnormalities, toxic myopathies, tetanus, electrolyte
      disturbances, inflammatory diseases, and exertion-related pain. A diagnosis of
      tension myalgia or myofascial-type pain is often considered when no objective
      findings are seen in the evaluation. This is a report of a patient who was
      treated unsuccessfully for fibromyalgia for many years and who ultimately was
      diagnosed with a rare benign skeletal muscle metabolic disorder caused by
      myoadenylate deaminase deficiency. We discuss this enzyme deficiency and its
      importance for the physiatric community.

PMID- 9014968
TI  - Reflex sympathetic dystrophy treated with gabapentin.
AB  - The use of the recently released anticonvulsant, gabapentin (Neurontin), in the
      treatment of severe and refractory reflex sympathetic dystrophy (RSD) pain in six
      patients ranging in age from 42 to 68 years is reported. Satisfactory pain relief
      obtained in all six patients suggests that this medication is an effective
      treatment for RSD pain. In addition to pain control, early evidence of disease
      reversal in these patients is suggested. Patient 6 is the first documented case
      of successful treatment and cure of the RSD pain syndrome using gabapentin alone.
      Specifically, reduced hyperpathia, allodynia, hyperalgesia, and early reversal of
      skin and soft tissue manifestations were noted. Gabapentin was chosen because it
      has properties similar to other anticonvulsant drugs and because previous studies
      have shown that it is well tolerated and appears to have a benign efficacy-to
      toxicity ratio. It was considered an acceptable and compassionate therapeutic
      choice because previous medical and surgical approaches had been ineffective for
      these patients, who represent the first case series documenting the use of
      gabapentin for pain management. Presently, the mechanism of pain relief in these
      patients is unknown. In this article, the pathophysiology of RSD is discussed,
      and a mechanism by which gabapentin provides pain relief is proposed. In view of
      encouraging results in these and other RSD patients, further scientific
      investigation is needed to delineate the role of gabapentin in the treatment of
      reflex sympathetic dystrophy.

PMID- 9014969
TI  - Transtibial prosthesis for a patient with Kaposi's sarcoma lesions on the
      residual limb.
AB  - A man with acquired immunodeficiency syndrome (AIDS) and widespread Kaposi's
      sarcoma (KS) presented with a transtibial amputation secondary to foot infection
      and intractable pain. Several open and draining KS lesions were present on the
      residual limb. There were two concerns: (1) prescribing a prosthesis to a person
      who likely had a limited future as a prosthetic user; and (2) how the lesions
      would tolerate pressure and shear forces in a prosthesis. There have been no
      previous reports of KS lesions of residual limbs. We prescribed a patellartendon
      bearing prosthesis with supracondylar suspension. The lesions did not worsen with
      weight-bearing, and healed with concomitant treatment. The patient remains a
      functional ambulator 1 year after amputation. This case suggests that KS lesions
      can tolerate pressure and shear forces, which is important in considering
      prosthetic prescriptions as well as prescriptions of orthoses and other devices.

PMID- 9014970
TI  - Tricyclic antidepressant in TBI.

PMID- 9014971
TI  - Additive beneficial effects of beta-blockers to angiotensin-converting enzyme
      inhibitors in the Survival and Ventricular Enlargement (SAVE) Study. SAVE
      Investigators.
AB  - OBJECTIVES: This study assessed whether treatment with a beta-adrenergic blocking
      agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor
      captopril decreases cardiovascular mortality and morbidity in patients with
      asymptomatic left ventricular dysfunction after myocardial infarction (MI) and
      whether the presence of neurohumoral activation at the time of hospital discharge
      predicts the effects of beta-blocker treatment in these patients. BACKGROUND:
      Both beta-blockers and ACE inhibitors have been shown to have beneficial effects
      in patients with left ventricular dysfunction but no overt heart failure after
      MI. These patients often have persistent neurohumoral activation at the time of
      hospital discharge, and one would expect that patients with activation of the
      sympathetic nervous system derive the most benefit from treatment with beta
      blockers. However, beta-blockers are underutilized in this high risk group of
      patients, and it is unknown whether their beneficial effects are additive to
      those of ACE inhibitors. METHODS: We performed a retrospective analysis of data
      from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral
      substudy. The relations between beta-blocker use at the time of randomization and
      neurohumoral activation and the subsequent development of cardiovascular events
      were analyzed by use of Cox proportional hazards models controlling for
      covariates. RESULTS: After adjustment for baseline imbalances, beta-blocker use
      was associated with a significant reduction in risk of cardiovascular death (30%,
      95% confidence interval [CI] 12% to 44%) and development of heart failure (21%,
      95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was
      not significant. These reductions were independent of the use of captopril. Beta
      blockers were not found to have a greater effect in patients with neurohumoral
      activation at the time of hospital discharge. CONCLUSIONS: The beneficial effects
      of beta-blocker use at the time of hospital discharge in patients with
      asymptomatic left ventricular dysfunction after MI appear to be additive to those
      of captopril and other interventions known to improve prognosis. Neurohumoral
      activation at the time of hospital discharge fails to identify those patients who
      will derive the greatest benefit from treatment with beta-blockers.

PMID- 9014972
TI  - Beta-adrenergic blocking agents or angiotensin-converting enzyme inhibitors, or
      both, for postinfarction patients with left ventricular dysfunction.

PMID- 9014973
TI  - Coronary revascularization surgery after myocardial infarction: impact of bypass
      surgery on survival after thrombolysis. GUSTO Investigators. Global Utilization
      of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.
AB  - OBJECTIVES: This study sought to investigate the impact of surgical
      revascularization on outcome after myocardial infarction. BACKGROUND: Small
      variations in rates of coronary artery bypass graft surgery (CABG) were noted
      among thrombolytic regimens in the Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, prompting the
      question of whether survival differences were partly related to differences in
      CABG rates. METHODS: Patients in the GUSTO trial were randomized to one of four
      thrombolytic strategies. Of 40,861 patients with complete data, 3,526 underwent
      surgical revascularization during their initial hospital admission. Thirty-day
      and 1-year mortality rates were estimated using Kaplan-Meier techniques, and the
      impact of CABG as a time-dependent covariate on death was evaluated using a Cox
      survival model, adjusting for baseline prognostic factors. RESULTS: The median
      time from study enrollment to CABG was 7 days across treatment groups. A 15%
      reduction in mortality for the tissue-type plasminogen activator (t-PA)-treated
      group was evident by the seventh day. Bypass surgery was a significant
      independent predictor of 30-day mortality (risk ratio 1.87) and a weaker
      predictor of 1-year mortality (risk ratio 1.21). Operative mortality was highest
      in patients with acute mitral regurgitation, ventricular septal defect or poor
      left ventricular function and in those undergoing CABG within the first 4 days of
      randomization. CONCLUSIONS: The survival benefit of accelerated t-PA was not
      related to surgical revascularization. Bypass surgery was associated with excess
      mortality in the first year, but the added short-term mortality associated with
      CABG may be balanced by anticipated long-term benefit in specific groups of
      patients.

PMID- 9014974
TI  - Association between activity at onset of symptoms and outcome of acute myocardial
      infarction.
AB  - OBJECTIVES: This study sought to compare the clinical features and outcome of a
      first myocardial infarction with onset of symptoms during or within 30 min of
      exercise, at rest and in bed. BACKGROUND: It is not known whether activity at
      onset influences outcome of acute myocardial infarction. METHODS: Information
      collected using a standard questionnaire was used to relate activity at the onset
      of symptoms to in-hospital outcome in 2,468 consecutive patients admitted to a
      coronary care unit with a first myocardial infarction between 1975 and 1993.
      RESULTS: Patients with exercise-related onset were more likely to be younger and
      male. Those with onset in bed were more likely to be older and have a history of
      stable or unstable angina. Compared with patients whose symptoms began at rest,
      those with exercise-related onset had a lower in-hospital mortality rate after
      adjusting for age, gender and year of admission (odds ratio [OR] 0.60, 95%
      confidence interval [CI] 0.40 to 0.89), and patients with onset in bed had a
      higher mortality rate (OR 1.38, 95% CI 1.03 to 1.85). The incidence of cardiac
      failure requiring diuretic therapy was also lower for exercise-related onset (OR
      0.83, 95% CI 0.67 to 1.04) and higher when onset was in bed (OR 1.36, 95% CI 1.11
      to 1.66). CONCLUSIONS: There is an association between activity at onset and
      outcome of acute myocardial infarction. Differences in pathophysiology or in the
      population at risk could explain this observation.

PMID- 9014975
TI  - Prognostic value of dobutamine-atropine stress echocardiography early after acute
      myocardial infarction. Echo Dobutamine International Cooperative (EDIC) Study.
AB  - OBJECTIVES: The aim of this multicenter, multinational, prospective,
      observational study was to assess the relative value of myocardial viability and
      induced ischemia early after uncomplicated myocardial infarction. BACKGROUND:
      Dobutamine-atropine stress echocardiography allows evaluation of rest function
      (at baseline), myocardial viability (at low dose) and residual ischemia (peak
      dose, up to 40 micrograms with atropine up to 1 mg) in one test. METHODS:
      Dobutamine-atropine stress echocardiography was performed 12 +/- 5 days (mean +/-
      SD) after a first uncomplicated acute myocardial infarction in 778 patients (677
      men; mean age 58 +/- 10 years) with technically satisfactory rest
      echocardiographic study results. Patients were followed-up for 9 +/- 7 months.
      RESULTS: Dobutamine-atropine stress echocardiographic findings were positive for
      myocardial ischemia in 436 of patients (56%) and negative in 342 (44%). During
      follow-up, there were 14 cardiac-related deaths (1.8% of the total cohort), 24
      (2.9%) nonfatal myocardial infarctions and 63 (8%) hospital readmissions for
      unstable angina. One hundred seventy-four patients (22%) underwent coronary
      revascularization (bypass surgery or coronary angioplasty). Spontaneous events
      occurred in 61 of 436 patients with positive and 40 of 342 patients with negative
      findings on dobutamine-atropine stress echocardiography (14% vs. 12%, p = 0.3).
      When only spontaneously occurring events were considered, the most important
      predictor was myocardial viability (chi-square 9.7). Using the Cox proportional
      hazards model, only the presence of myocardial viability (hazard ratio [HR] 2.0,
      p < 0.002) and age (HR 1.03, p < 0.001) were predictive of spontaneously
      occurring events. When only hard cardiac events were considered, age was the
      strongest predictor (chi-square 3.6, p = 0.056), followed by wall motion score
      index (WMSI) at peak dose (chi-square 3.3, p = 0.06) and remote ischemia (chi
      square 2.25, p = 0.1). When cardiac death was considered, WMSI at peak dose was
      the best predictor (HR 9.2, p < 0.0001). CONCLUSIONS: During dobutamine stress,
      echocardiographic recognition of myocardial viability is more prognostically
      important than echocardiographic recognition of myocardial ischemia for
      predicting unstable angina, whereas WMSI at peak stress was the best predictor of
      cardiac-related death. Different events can be recognized with different
      efficiency by various stress echocardiographic variables.

PMID- 9014976
TI  - Prognostic value of dobutamine echocardiography early after uncomplicated acute
      myocardial infarction: a comparison with exercise electrocardiography.
AB  - OBJECTIVES: This study sought to assess the relative prognostic power of
      dobutamine echocardiography and exercise electrocardiography after acute
      myocardial infarction. BACKGROUND: The prognostic value of dobutamine
      echocardiography early after acute myocardial infarction has not yet been
      reported. METHODS: One hundred seventy-eight patients (mean age 58 +/- 9 years)
      with a first uncomplicated acute myocardial infarction underwent predischarge
      dobutamine echocardiography (5 to 40 micrograms/kg body weight per min, plus
      atropine if needed) and symptom-limited bicycle exercise electrocardiography and
      were followed up for 17 +/- 13 months. Stress-induced dyssynergy and ST segment
      depression > 1 mm were considered criteria of positivity for dobutamine
      echocardiography and exercise electrocardiography, respectively. RESULTS:
      Dobutamine echocardiography was positive in 83 patients and exercise
      electrocardiography in 60. At follow-up there were 5 deaths, 6 nonfatal
      myocardial infarctions (11 hard events) and 20 cases of unstable angina.
      Dobutamine echocardiography and exercise electrocardiography had similar negative
      predictive values both for all events (88% and 86%, respectively) and for hard
      events (98% and 95%, respectively). The hard events rate was significantly higher
      in patients with positive rather than negative dobutamine echocardiography
      (relative risk [RR] 5.15, 95% confidence interval [CI] 1.14 to 23.16), although
      there was no difference between patients with positive and negative exercise
      electrocardiograms. When Cox analysis was performed, dobutamine echocardiography
      had an independent prognostic value both for all events (RR 2.88, 95% CI 1.37 to
      6.08) and for hard events (RR 6.56, 95% CI 1.42 to 30.46). CONCLUSIONS: After
      uncomplicated acute myocardial infarction, dobutamine echocardiography and
      exercise electrocardiography have a similar high negative predictive value for
      both all events and hard events only. Positive dobutamine echocardiography, but
      not positive exercise electrocardiography, identifies a group of patients at
      higher risk of subsequent cardiac events.

PMID- 9014977
TI  - Determinants and correlates of target lesion calcium in coronary artery disease:
      a clinical, angiographic and intravascular ultrasound study.
AB  - OBJECTIVES: This report used intravascular ultrasound and quantitative coronary
      angiography to explore the relation between lesion-associated calcium and risk
      factors, clinical presentation and angiographic severity of coronary artery
      stenoses. BACKGROUND: Coronary artery calcium is a marker for significant
      coronary atherosclerosis. Noninvasive procedures are being proposed as screening
      tests for coronary artery disease. Intravascular ultrasound identification of
      tissue calcium has been validated in vitro. METHODS: Independent chart review,
      preintervention intravascular ultrasound imaging and coronary angiography were
      used to study primary native vessel lesions in 1,442 patients. Target lesions and
      reference segments were evaluated according to previously published quantitative
      and qualitative methods. Results are presented as mean value +/- SD. RESULTS:
      Overall, 1,043 lesions contained target lesion calcium (72%); the arc of target
      lesion calcium was 110 +/- 109 degrees. Lesions with an ultrasound plaque burden
      > 0.75 or an angiographic diameter stenosis > 0.25 had a prevalence of calcium of
      at least 65%, with a mean arc > 100 degrees. Intermediate lesions had as much
      target lesion calcium as did angiographically severe lesions. Using multivariate
      linear regression analysis, patient age, stable (vs. unstable) angina and the
      intravascular ultrasound lesion site and reference segment plaque burden (but not
      the angiographic diameter stenosis) were the independent predictors of the arc of
      target lesion calcium (all p < 0.0001). CONCLUSIONS: Intravascular ultrasound
      analysis shows that coronary calcification correlates with plaque burden but not
      with degree of lumen compromise. Thus, the noninvasive detection of coronary
      calcium is predictive of future cardiac events, presumably because coronary
      calcification is a marker for overall atherosclerotic plaque burden. Coronary
      calcium increases with increasing patient age and is less common in unstable
      lesion subsets.

PMID- 9014978
TI  - Clinical, angiographic and hemodynamic predictors of recruitable collateral flow
      assessed during balloon angioplasty coronary occlusion.
AB  - OBJECTIVES: We sought to determine the predictive value of factors influencing
      coronary collateral vascular responses in humans. BACKGROUND: There is limited
      information on the factors responsible for coronary collateral vascular
      development, despite the protective effect of collateral vessels in ischemic
      syndromes. METHODS: Angiography of the contralateral artery was performed during
      balloon coronary occlusion in 105 patients with single-vessel disease (left
      anterior descending coronary artery in 69 patients, left circumflex coronary
      artery in 4 patients, right coronary artery in 32 patients) and normal left
      ventricular function. Collateral vessels were graded according to the
      classification of Rentrop. The relative collateral vascular resistance was
      calculated in a subgroup of 34 patients by means of aortic pressure, coronary
      wedge pressure and collateral flow, defined as the transient increase of coronary
      blood flow velocity of the contralateral artery during balloon coronary
      occlusion. Ischemia during coronary occlusion was evaluated by the ST segment
      shift (mV) in a 12-lead electrocardiogram (ECG). RESULTS: A multivariate logistic
      analysis of clinical and angiographic variables revealed duration of angina (> or
      = 3 months, p < 0.0001), lesion severity (> or = 75% diameter stenosis, p <
      0.0001) and proximal lesion location (p = 0.02) as independent factors positively
      associated with recruitability of collateral vessels, whereas the use of nitrates
      exerted an independent negative effect (p = 0.01). The regression equation
      yielded an overall predictive accuracy of 80%. The presence of recruitable
      collateral vessels during coronary occlusion resulted in a higher coronary
      wedge/aortic pressure ratio (mean [+/- SD] 0.35 +/- 0.13 vs. 0.27 +/- 0.12, p <
      0.005), a lower relative collateral vascular resistance (6.7 +/- 7.4 vs. 21.3 +/-
      10, p < 0.001) and a reduction of ECG signs of ischemia (0.14 +/- 0.19 vs. 0.38
      +/- 0.33 mV, p < 0.001). The relative collateral vascular resistance was the best
      predictor for recruitability of collateral vessels compared with the other
      variables related to collateral vascular growth (p < 0.05). CONCLUSIONS: Clinical
      and angiographic variables predict recruitability of collateral vessels with an
      80% overall accuracy. These findings are important for risk stratification of
      patients undergoing interventions for ischemic coronary syndromes.

PMID- 9014979
TI  - Accuracy of Doppler catheter measurements: effect of inhomogeneous beam power
      distribution on mean and peak velocity.
AB  - OBJECTIVES: We sought to determine the effect of inhomogeneous distribution of
      beam power produced by Doppler catheters on measurements of mean and peak
      velocity of coronary blood flow. BACKGROUND: Measurements of mean velocity of
      coronary blood flow by Doppler catheters have significant systematic errors that
      have not been completely characterized. We hypothesized that one error is the
      inhomogeneous distribution of the ultrasonic beam power and that this
      inhomogeneity makes measurements of mean, but not peak, velocity inaccurate.
      METHODS: We constructed a scaled-up model of a Doppler catheter to allow for
      accurate measurement of the distribution of beam power by miniature hydrophones.
      This catheter was placed in a model of coronary blood flow in which the fluid
      velocity was accurately measured by an external laser Doppler velocimeter. The
      laser Doppler measurements of mean velocity were compared with the measurements
      of mean velocity made by the catheter, using fast Fourier transform analysis,
      both without and with correction for inhomogeneous beam power distribution. Peak
      velocity measurements were also compared, as predicted from theory, without the
      need of correction for inhomogeneous beam power distribution. To investigate the
      clinical relevance of our results, we conducted studies using a clinical Doppler
      catheter both in a scaled model of coronary flow and in a series of eight
      patients. In the model and in each patient, we rotated the catheter without
      changing the axial position to systematically alter the relation of the beam
      power distribution to the local fluid dynamics. RESULTS: The measurement of beam
      power distribution revealed significant inhomogeneity. Comparison of the measured
      mean frequency shifts without correction for inhomogeneities in the distribution
      yielded a statistically significant difference. After correction for
      inhomogeneities, there was no statistically significant difference. Also, there
      was no significant difference for the peak frequency shifts. Rotation of the
      clinical catheter in the scaled model and in the patients changed the measured
      mean velocity (average change 18.8% and 20.6%, respectively), but not the
      measured peak velocity (average change 5.0% and 4.3%, respectively). CONCLUSIONS:
      For signal analysis using a fast Fourier transform, the inhomogeneous
      distribution of power of the ultrasonic beam produced by Doppler catheters makes
      measurements of mean, but not peak, velocity inaccurate. Measurements of peak
      velocity may therefore prove superior to measurements of mean velocity in
      estimating the response to pharmacologic intervention and in estimating stenosis
      severity.

PMID- 9014980
TI  - Investigation of the mechanism of chest pain in patients with angiographically
      normal coronary arteries using transesophageal dobutamine stress
      echocardiography.
AB  - OBJECTIVES: The present study sought to determine whether myocardial contractile
      abnormalities accompany the development of chest pain in patients with normal
      coronary angiograms. BACKGROUND: The mechanism of chest pain in patients with
      angina despite a normal coronary arteriogram is controversial. Although previous
      studies postulated the existence of coronary microvascular dysfunction, others
      failed to find evidence of myocardial ischemia, and recent studies have
      demonstrated abnormal cardiac sensitivity in these patients that can lead to
      chest pain on a nonischemic basis. METHODS: Seventy patients (26 men and 44
      women, mean age 49 +/- 10 years) with angina-like chest pain and angiographically
      normal coronary arteries underwent exercise treadmill testing, radionuclide
      angiography at rest and during exercise, thallium stress testing and
      transesophageal dobutamine stress echocardiography. The results of exercise
      treadmill testing and stress echocardiography were compared with those obtained
      in 26 normal control subjects (19 men and 7 women, mean age 56 +/- 7 years).
      RESULTS: Abnormalities consistent with myocardial ischemia were noted in 31% of
      the patients during exercise treadmill testing, in 16% during exercise
      radionuclide angiography and in 18% during thallium stress testing. The findings
      of the radionuclide studies were not concordant with one another and were not
      related to the presence of repolarization changes during exercise testing. During
      infusion of dobutamine, chest pain developed in 59 patients (84%) and in none of
      the control subjects (p < 0.0001); repolarization changes occurred in 22 patients
      (34%) and in 2 control subjects (8%) (p < 0.04). None of the patients or the
      control subjects developed regional wall motion abnormalities with dobutamine.
      The quantitative myocardial contractile response to dobutamine was similar in
      patients and control subjects, with an 80% power to detect a 25% difference in
      systolic wall thickening at the maximal dose of dobutamine. CONCLUSIONS: There
      was no agreement in the results of noninvasive tests in our patients. Despite the
      frequent provocation of chest pain and electrocardiographic abnormalities with
      dobutamine, the patients demonstrated a quantitatively normal myocardial
      contractile response without development of wall motion abnormalities. These
      observations strongly suggest that myocardial ischemia is not the cause of chest
      pain in patients with a normal coronary arteriogram.

PMID- 9014981
TI  - William Heberden revisited: postprandial angina-interval between food and
      exercise and meal composition are important determinants of time to onset of
      ischemia and maximal exercise tolerance.
AB  - OBJECTIVES: This study aimed to explore the hemodynamic responses to ingestion of
      meals of different composition in patients with chronic stable angina and to
      assess the effect of these meals on time to onset of > 1-mm ST segment depression
      and limiting angina pectoris during exercise. BACKGROUND: To our knowledge, no
      study has assessed the effect of meal composition and timing of exercise in
      patients with coronary artery disease. METHODS: Fifteen patients with chronic
      stable angina visited our laboratory in the fasted state on three occasions.
      Measurements of cardiac output, heart rate and blood pressure were taken while
      patients were standing. A modified Bruce exercise test was then carried out,
      during which time to onset of > 1-mm ST segment depression and limiting chest
      pain were recorded. Patients then ate a 2.5-MJ high fat or high carbohydrate
      meal; on the third occasion, no meal was taken. At 30 min and 1 h after eating
      the meals, rest hemodynamic measurements and exercise tests were repeated.
      RESULTS: The high fat meal did not affect exercise variables, whereas the high
      carbohydrate meal resulted in a reduction in time to onset of ST segment
      depression of 74.4 +/- 22.2 s (mean +/- SEM) during exercise at 30 min (p <
      0.01), and at both 30 and 60 min after the high carbohydrate meal, limiting chest
      pain occurred 50 to 90 s earlier than when patients fasted (p < 0.01).
      CONCLUSIONS: One hour after a high carbohydrate meal, the onset of angina during
      exercise occurs earlier than in the fasted state. Despite similar hemodynamic
      adjustments, a high fat meal does not affect exercise time.

PMID- 9014982
TI  - Nitric oxide activity in the atherosclerotic human coronary circulation.
AB  - OBJECTIVES: We determined the activity of nitric oxide at rest and after
      acetylcholine in the atherosclerotic human coronary circulation. BACKGROUND:
      Although responses to acetylcholine, an endothelium-dependent vasodilator, are
      abnormal in patients with coronary atherosclerosis, whether this reflects
      abnormal nitric oxide activity in humans in vivo has not been investigated
      previously. METHODS: We investigated the effects of intracoronary L-NG-monomethyl
      arginine (L-NMMA), a specific antagonist of nitric oxide synthesis, on coronary
      vascular resistance and epicardial coronary artery diameter at rest and after
      acetylcholine in 24 patients with coronary artery disease and in 12 subjects with
      angiographically normal coronary arteries who were free from atherosclerotic risk
      factors. RESULTS: With L-NMMA, the 13 +/- 4% (mean +/- SEM) increase in coronary
      vascular resistance and the 4 +/- 1% lumen diameter narrowing in atherosclerotic
      patients were lower than the 38 +/- 9% increase in resistance and the 15 +/- 2%
      decrease in diameter (both p < 0.01) observed in normal control subjects,
      indicating reduced basal nitric oxide activity in atherosclerosis. The degree of
      angiographic atherosclerotic narrowing did not correlate with the magnitude of
      diameter reduction. Acetylcholine-induced coronary epicardial and microvascular
      dilation was also depressed in atherosclerotic patients (32.2 +/- 9% reduction in
      coronary vascular resistance with 10(-6) mol/liter acetylcholine) compared with
      normal control subjects (65.5 +/- 2% decrease, p < 0.01). L-NMMA inhibited
      acetylcholine-induced epicardial and microvascular vasodilation in both patient
      groups, but the inhibition was greater in normal control subjects than in
      atherosclerotic patients, indicating that stimulation of nitric oxide activity by
      acetylcholine is reduced in atherosclerotic patients compared with normal control
      subjects. Coronary vascular dilation with sodium nitroprusside was similar in
      both groups and was not suppressed by L-NMMA. Furthermore, L-arginine reversed
      the constrictor effects of L-NMMA, indicating that the action of L-NMMA is
      specifically caused by inhibition of nitric oxide production from L-arginine.
      CONCLUSIONS: These findings indicate that 1) there is a reduced basal activity of
      nitric oxide in the human atherosclerotic epicardial and microvascular coronary
      circulation; and 2) acetylcholine-induced coronary vascular dilation is at least
      partly due to stimulation of the activity of nitric oxide, and the reduced
      response to acetylcholine is due to attenuation in the stimulated activity of
      nitric oxide in patients with atherosclerosis.

PMID- 9014983
TI  - Atherosclerosis in the human brachial artery.
AB  - OBJECTIVES: We sought to assess the prevalence of atherosclerotic lesions in the
      human brachial artery. BACKGROUND: Many investigators have recently studied
      endothelial and vascular function in the brachial circulation in humans to
      further their understanding of coronary artery disease and early atherogenesis.
      However, the prevalence of brachial atherosclerosis and its relation to coronary
      disease have never been documented. METHODS: Arterial segments from the brachial,
      common carotid and left anterior descending coronary arteries were obtained
      during autopsy in 52 consecutively examined subjects (35 men, 17 women; 21 to 79
      years old, mean [+/-SD] age 51 +/- 16) and studied by light microscopy using
      standard histologic techniques. Severity of the atherosclerotic lesions was
      categorized as fatty streaks (grade 1), fibrous plaques (grade 2) and advanced
      lesions (grade 3). RESULTS: Atherosclerotic lesions of any grade were found in
      the brachial artery in 39 (75%) subjects, common carotid artery in 51 (98%) and
      left anterior descending coronary artery in 52 (100%), and the prevalence and
      severity of disease increased with age in all three arteries. The grade of lesion
      severity in the brachial and coronary arteries was significantly correlated (r =
      0.41, p = 0.003), as was severity in the brachial and carotid arteries (r = 0.53,
      p = 0.0001) and the carotid and coronary arteries (r = 0.69, p = 0.0001). The
      correlation between the brachial artery and the left anterior descending coronary
      artery was highly significant in subjects < or = 50 years old (r = 0.54, p =
      0.002), but not in those > or = 50 years old (r = 0.37, p = NS). CONCLUSIONS:
      Atherosclerosis is common in the human brachial artery and is significantly
      correlated with both coronary and carotid disease. These results suggest that the
      brachial circulation may serve as a reasonable "surrogate" for studying
      atherosclerosis, particularly in younger adults.

PMID- 9014984
TI  - Outpatient coronary stent implantation.
AB  - OBJECTIVES: This study was performed to explore the feasibility of coronary
      Palmaz-Schatz stent implantation on an outpatient basis. BACKGROUND: To optimize
      the applicability of coronary stenting by limiting bleeding complications and
      length of hospital stay, the transradial approach has been demonstrated to be an
      effective technique. Immediate ambulation opens the way to outpatient treatment.
      METHODS: Patients selected for Palmaz-Schatz stent implantation received
      anticoagulation with Coumadin. At an international normalized ratio > 2.5,
      stenting was performed through the radial approach. Starting in December 1994,
      patients were treated with Ticlopidin. Heparin was administered during the
      procedure. Suitability for same-day discharge was assessed on the basis of
      preprocedural, postprocedural and periprocedural criteria. Patients were
      mobilized after immediate sheath removal, followed by same-day discharge. Follow
      up examinations were performed the next day, at 2 weeks and at 1 month after
      stenting. RESULTS: Of 188 patients who underwent Palmaz-Schatz coronary stent
      implantation through the radial artery between May 1994 and July 1995, 88
      remained in the hospital for various reasons. In the 100 outpatients (Canadian
      Cardiovascular Society classes III and IV, n = 90 [90%]), 125 stents had been
      implanted to cover 110 lesions. No cardiac or bleeding events were encountered
      within 24 h (95% confidence interval 0 to 3.6) of stenting. At 2-week follow-up,
      one patient was readmitted (day 4) because of a bleeding abdominal aortic
      aneurysm requiring operation. Two patients were readmitted 2 weeks after
      discharge, one with subacute thrombosis and one with angina and anemia that was
      treated with blood transfusions. At 1-month follow-up, no complications were
      observed. CONCLUSIONS: After an optimal transradial Palmaz-Schatz coronary stent
      result, patients can safely be discharged on the day of treatment.

PMID- 9014985
TI  - Restenosis of endovascular stents from stent compression.
AB  - OBJECTIVES: We sought to determine the basis for restenosis within superficial
      femoral arteries (SFAs) and hemodialysis conduits treated with balloon-expandable
      stents. BACKGROUND: Use of stents within coronary and peripheral vessels
      continues to increase exponentially. The mechanism of restenosis within stents
      placed at various vascular sites is not well understood. In particular, the
      implications of deploying a balloon-expandable stent in a compressible site are
      not well understood. METHODS: After the serendipitous detection of stent
      deformation during intravascular ultrasound (IVUS) examination of a restenosed
      dialysis fistula, we evaluated a consecutive series of patients with stents
      placed in compressible vascular sites, including the SFA (six patients) and
      hemodialysis fistulae (five patients). Clinical, angiographic and IVUS
      examinations were performed to evaluate mechanisms of restenosis. RESULTS: Stent
      compression was identified as the principal cause of restenosis in all dialysis
      conduits and SFAs. Stent deformity was not reliably identified by angiography;
      however, IVUS identified compression of two forms: eccentric deformation,
      implicating two-point compressive force, and complete circumferential
      encroachment of stent struts around the catheter, suggesting multidirectional
      compressive force. Despite redilation, secondary restenosis resulting from
      recurrent compression recurred in most sites. CONCLUSIONS: Restenosis within
      balloon-expandable endovascular stents may occur as a result of stent
      compression, a phenomenon readily detected by IVUS, but often not by angiography.
      These findings have significant implications for the use of balloon-expandable
      stents within vascular sites subject to extrinsic compression, such as
      hemodialysis conduits, the adductor canal segment of the SFA and carotid
      arteries.

PMID- 9014986
TI  - Coronary angioplasty for elderly patients with "high risk" unstable angina: short
      term outcomes and long-term survival.
AB  - OBJECTIVES: We sought to compare the short- and long-term mortality rates in
      patients > or = 70 years old with unstable angina undergoing percutaneous
      transluminal coronary angioplasty (PTCA) with predicted coronary artery bypass
      graft surgery (CABG) short-term and U.S. census long-term mortality rates.
      BACKGROUND: Coronary angioplasty is an alternative revascularization strategy for
      patients with medically refractory rest angina and a high risk of adverse
      outcomes with CABG. Patients > or = 70 years old are a specific high risk subset.
      METHODS: A total of 131 consecutive patients aged > or = 70 years with unstable
      angina underwent PTCA; 82 (62%) of 131 had been refused CABG. Mortality over time
      was obtained from the Veterans Affairs Beneficiary Index Records Locator
      Subsystem. Predicted 30-day CABG-associated mortality was obtained from the
      Veterans Affairs Cardiac Risk Assessment Model. Mortality over time was expressed
      with Kaplan-Meier curves. RESULTS: The observed 30-day angioplasty survival rate
      was 87% compared with the predicted surgical 30-day survival rate of 85.5%. In
      those patients who survived 6 months after angioplasty (84%), their subsequent 1
      , 2-, 3-, 4- and 5-year survival rates were comparable to age-matched subjects in
      the U.S. census. Mortality in certain subsets known to be at very high risk for
      CABG-for example, patients who had a previous CABG-was not high in this cohort of
      elderly subjects. The extremely high risk subsets identified in this PTCA cohort
      (shock, heart failure, pressors required, balloon pump required) were relatively
      infrequent subsets. CONCLUSIONS: For selected elderly patients with unstable
      angina deemed to be at "high risk" or even "prohibitive risk" for CABG, PTCA is
      an alternative revascularization strategy. The long-term mortality of
      successfully treated elderly patients is comparable to age-matched subjects. A
      prospective, multicenter, randomized trial of CABG versus PTCA, which includes
      patients > or = 70 years old, is being conducted (Veterans Affairs Cooperative
      Study 385: AWESOME).

PMID- 9014987
TI  - Percutaneous treatment of protected and unprotected left main coronary stenoses
      with new devices: immediate angiographic results and intermediate-term follow-up.
AB  - OBJECTIVES: We sought to evaluate the immediate angiographic results and
      intermediate-term follow-up after percutaneous treatment of left main coronary
      stenoses in the new device era. BACKGROUND: Historically, balloon angioplasty of
      left main coronary stenoses has been associated with high procedural morbidity
      and poor long-term results. It is not clear whether new devices are more
      effective in this anatomic setting. METHODS: Between July 1993 and July 1995, we
      performed initial left main coronary interventions on 46 patients (mean age 67 +/
      12 years, 26% women). Quantitative angiography was available for 42 of 46
      interventions, and clinical follow-up was obtained for all patients at 1 month, 6
      months and 1 year after initial revascularization. RESULTS: Most interventions
      (42 of 46) were performed in patients with "protected" coronary stenoses to the
      left coronary system owing to the presence of one or more patent left main
      coronary grafts. Seventy-seven percent of screened patients were deemed
      unsuitable for repeat coronary artery bypass surgery. Procedures performed
      included stenting in 73% of patients (alone in 30% and after rotational
      atherectomy in 43%), rotational atherectomy in 58% (alone in 15% and before
      stenting in 43%), directional atherectomy in 4% and angioplasty alone in 7%.
      Initial procedural success was achieved in all interventions, with no deaths,
      myocardial infarctions (creatine kinase, MB fraction > 50 IU/liter) or emergent
      bypass surgery. Follow-up data to date (median duration 9 months, range 6 to 19)
      demonstrate a 98% overall survival rate and a 6-month event-free survival rate of
      78% (six target vessel revascularizations [TVRs], four non-TVRs). CONCLUSIONS:
      Treatment of protected left main coronary artery stenoses can be accomplished
      safely and effectively with new device technology. Intermediate-term follow-up
      demonstrates an acceptably low rate of death, myocardial infarction or repeat
      revascularization at 6 months and 1 year.

PMID- 9014988
TI  - Comparison of early and recent results with rotational atherectomy.
AB  - OBJECTIVES: We compared an early registry of rotational atherectomy with a recent
      registry to examine the evolution of patient profiles, lesion characteristics and
      procedural outcomes for patients treated with rotational atherectomy. BACKGROUND:
      With increased experience, the selection of patients and lesions treated with a
      device matures. This study documents the changes in the application of rotational
      atherectomy. METHODS: The patient characteristics and procedural outcomes from
      two multicenter patient registries-Registry I: 2,953 procedures, 3,717 lesions
      from 1988 to 1993; and Registry II: 200 procedures, 268 lesions from 1994-were
      analyzed and compared. RESULTS: There was an increase in the average age of the
      patients (63 vs. 65 years, p < 0.02) and the proportion of patients with unstable
      angina (42.9% vs. 56.5%, p < 0.01) or previous coronary artery bypass graft
      surgery (18.8% vs. 24.5%, p < 0.05) in Registry II. Registry II included fewer
      left anterior descending coronary lesions (46.5% vs. 32.8%, p < 0.01), more type
      B and C lesions (83.1% vs. 91.8%, p < 0.01), more eccentric lesions (69.0% vs.
      79.5%, p < 0.01) and more calcified lesions (50.3% vs. 69.4%, p < 0.01).
      Complications, including urgent bypass surgery, Q and non-Q wave myocardial
      infarction, dissection, acute occlusion and perforation, were similar in the two
      groups. However, mortality increased from 1.0% to 3.0% (p < 0.05) in Registry II.
      CONCLUSIONS: Comparison of recent and early patients treated with rotational
      atherectomy revealed an increase in the complexity of patients and lesions.
      Although the rate of death was increased, the overall rate of major complications
      was not significantly changed (4.7% vs. 6.0%, p = NS).

PMID- 9014989
TI  - Long-term survival of African Americans in the Coronary Artery Surgery Study
      (CASS).
AB  - OBJECTIVES: This study sought to determine the long-term (> 15 years) outcome of
      a clinically well characterized cohort of African Americans with known or
      suspected coronary artery disease (CAD). BACKGROUND: The mortality rate from CAD
      is higher in African Americans than in whites. An earlier analysis of data from
      the Coronary Artery Surgery Study (CASS) registry suggested that African American
      and white patients treated surgically had equal 5-year survival rates. METHODS:
      Survival data from the CASS registry were analyzed to determine whether 1)
      African American race is an independent predictor of mortality; and 2) initial
      therapy is predictive of mortality among African American patients. RESULTS:
      Overall, 60% of white and 52% of African American patients survived 16 years (p <
      0.00001). Multivariate Cox models confirmed that African American race was
      independently associated with higher mortality in both the medical group (hazard
      ratio [HR] 1.34, 95% confidence interval [CI] 1.11 to 1.63) and the surgical
      group (HR 1.63, 95% CI 1.19 to 2.23). Initial therapy was not predictive of
      survival among African American patients (p = 0.81). However, smoking status
      significantly influenced survival: African Americans who did not smoke
      experienced significantly improved survival (60% vs. 48% for smokers), which
      equaled survival for white nonsmokers (61%, p = NS). CONCLUSIONS: In contrast to
      results from shorter term studies, African Americans experienced higher overall
      mortality rates than whites over the long term, regardless of the type of initial
      treatment. Survival among nonsmoking African Americans at 16 years equaled
      survival among nonsmoking whites.

PMID- 9014990
TI  - Deletion polymorphism of angiotensin-converting enzyme gene and left ventricular
      hypertrophy in southern Italian patients.
AB  - OBJECTIVES: This study sought to evaluate the possible association of
      polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure
      and left ventricular mass index (LVMI). BACKGROUND: The renin-angiotensin system
      seems to be involved in the pathogenesis of essential hypertension. Moreover,
      recent epidemiologic observations demonstrate that many subjects with left
      ventricular hypertrophy have normal blood pressure levels, suggesting that
      factors other than hemodynamic overload may contribute to the hypertrophy.
      METHODS: The study included 140 untreated hypertensive outpatients who underwent
      ambulatory blood pressure monitoring, echocardiographic evaluation and analysis
      for insertion (I)/ deletion (D) polymorphism in intron 16 of the ACE gene by
      polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was
      calculated by the Devereux formula, in each patient. RESULTS: Left ventricular
      mass index values (mean +/- SD) were 137 +/- 28 g/m2 in patients with the DD
      genotype, 125 +/- 27 g/m2 in those with the ID genotype and 115 +/- 27 g/m2 in
      those with II genotype. The frequencies of the DD, ID and II genotypes were
      45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in
      Hardy-Weinberg equilibrium. The strongest association between left ventricular
      mass and DD genotype in our cohort appeared to be an independent cardiovascular
      risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI]
      interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p
      < 0.02). CONCLUSIONS: Our data show that the LVMI was significantly enhanced in
      patients with the DD genotype.

PMID- 9014991
TI  - High incidence of appropriate implantable cardioverter-defibrillator therapy in
      patients with syncope of unknown etiology and inducible ventricular arrhythmias.
AB  - OBJECTIVES: This study evaluates the hypothesis that in patients with syncope of
      unknown origin, inducible ventricular arrhythmias are specific arrhythmias and
      therefore should be appropriately treated. BACKGROUND: Although syncope is a
      common clinical entity, the evaluation and treatment of patients with syncope
      without a clear etiology are not well defined. Many patients with syncope of
      undetermined origin undergo invasive electrophysiologic evaluation. Abnormalities
      of the sinus node, prolongation of conduction times or inducible arrhythmias
      found at these evaluations are usually assumed to be the cause of syncope and are
      therefore treated. However, whether tachyarrhythmias are truly the cause of
      syncope, and whether treatment of these tachyarrhythmias can prevent recurrent
      syncope and arrhythmic death, is unknown. METHODS: This study included 50
      consecutive patients with syncope of undetermined origin, ventricular
      tachyarrhythmias at electrophysiologic evaluation and treatment with an
      implantable cardioverter-defibrillator. RESULTS: Ventricular stimulation led to
      sustained monomorphic ventricular tachycardia in 36 patients, nonsustained
      ventricular tachycardia in 5 and ventricular fibrillation in 9. Over a 23 +/- 15
      month (mean +/- SD) follow-up period, 18 patients received appropriate
      implantable cardioverter-defibrillator shock. Actuarial probability of
      appropriate therapy was 22% at 1 year and 50% at 3 years. Recurrent syncope was
      seen in five patients, three of whom had appropriate defibrillatory detections at
      the time of syncope. Four patients died (sudden death in one, congestive heart
      failure in two). CONCLUSIONS: In patients with syncope of undetermined origin and
      inducible ventricular tachyarrhythmias, appropriate implantable cardioverter
      defibrillator therapy is common at follow-up. Sudden cardiac death is uncommon.
      This low incidence of sudden cardiac death and high incidence of appropriate
      defibrillator therapy support the current practice of using implantable
      cardioverter-defibrillators in patients with syncope of unknown origin and
      inducible ventricular arrhythmias.

PMID- 9014992
TI  - Mechanism of initiation of atrial flutter in humans: site of unidirectional block
      and direction of rotation.
AB  - OBJECTIVES: Using a standardized induction protocol, we investigated the
      mechanism of initiation of atrial flutter, before ablation, to determine the site
      of initiating unidirectional block and to test the hypothesis that the direction
      of rotation of atrial flutter depends on the pacing site from which it initiates.
      BACKGROUND: The high recurrence rate of atrial flutter after presumed successful
      ablation may be due to difficulty in reinduction after termination. In addition,
      induction of clockwise flutter is currently of unknown clinical importance.
      METHODS: Ten patients with documented typical flutter were studied before
      ablation. A standard protocol consisting of single and double extrastimuli
      followed by burst pacing was performed from four sites in the right atrium (high
      and low trabeculated and smooth right atrium) to assess efficacy at inducing
      atrial flutter. A 20-pole halo catheter placed around the tricuspid annulus and a
      decapole catheter placed in the coronary sinus were used for mapping during
      initiation to determine type of flutter induced and the site of unidirectional
      block during initiation. RESULTS: Atrial flutter was induced in 52 (6.2%) of 838
      attempted inductions. Of these, 33 were counterclockwise and 20 were clockwise.
      Of the 20 inductions resulting in clockwise flutter, 18 were from the
      trabeculated right atrium, whereas all the counterclockwise inductions were from
      the smooth right atrium. In all but the two inductions, the site of
      unidirectional block was identified between the os of the coronary sinus and the
      low lateral right atrium for both counterclockwise and clockwise flutter, in the
      same isthmus at which ablation is targeted. CONCLUSIONS: Even in patients with
      clinical counterclockwise flutter, clockwise flutter is frequently induced before
      ablation and is dependent on the site of induction: Pacing from the smooth right
      atrium induces counterclockwise flutter, whereas pacing from the trabeculated
      right atrium induces clockwise flutter. The site of the unidirectional block
      during the initiation of either form of flutter is in the low right atrium
      isthmus.

PMID- 9014994
TI  - Acute conversion of atrial fibrillation and flutter: direct current cardioversion
      versus intravenously administered pure class III agents.

PMID- 9014993
TI  - Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of
      sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators.
AB  - OBJECTIVES: This study sought to determine the safety and efficacy of a single
      bolus of intravenous dofetilide, a pure class III antiarrhythmic agent, for the
      termination of sustained atrial fibrillation or flutter. BACKGROUND: Dofetilide
      is a highly selective blocker of the rapid component of the delayed rectifier
      current causing action potential prolongation. These effects, and preliminary
      clinical data, suggest that it may be effective in the treatment of atrial
      fibrillation and flutter. METHODS: Ninety-one patients with sustained atrial
      fibrillation (75 patients) or flutter (16 patients) were entered into a double
      blind, randomized multicenter study of one of two doses of dofetilide (4 or 8
      micrograms/kg body weight) or placebo. RESULTS: Dofetilide effectively terminated
      the arrhythmia in 31% of patients receiving 8 micrograms/kg, a statistically
      significant difference from those receiving 4 micrograms/kg (conversion rate
      12.5%, p < 0.05) or placebo (no conversion, p < 0.01). Patients with atrial
      flutter had a greater response to dofetilide (54% conversion rate) than those
      with atrial fibrillation (14.5% conversion rate, p < 0.001). CONCLUSIONS:
      Intravenous dofetilide can convert sustained atrial fibrillation or flutter to
      sinus rhythm. However, its efficacy is greater in flutter--a response that
      contrasts with the poorer response seen with class I agents. This finding
      potentially represents an important advance in the pharmacologic termination of
      atrial flutter.

PMID- 9014995
TI  - A new electrocardiographic algorithm using retrograde P waves for differentiating
      atrioventricular node reentrant tachycardia from atrioventricular reciprocating
      tachycardia mediated by concealed accessory pathway.
AB  - OBJECTIVES: The purpose of this study was to use an electrocardiographic (ECG)
      algorithm, derived from the results of radiofrequency ablation, to discriminate
      atrioventricular node reentrant tachycardia (AVNRT) from atrioventricular
      reciprocating tachycardia (AVRT) and to localize a concealed accessory pathway,
      prospectively. BACKGROUND: Information about ECG criteria for differentiating
      AVNRT from AVRT is limited and has not been confirmed by surgical or catheter
      ablation. METHODS: Four hundred six ECGs (obtained from 406 different patients)
      that demonstrated narrow QRS complex (< 0.12 s) supraventricular tachycardia with
      an RP' interval less than the P'R interval or pseudo r' wave in lead V1 or pseudo
      S wave in inferior leads, or both, were examined, and the results were confirmed
      by radiofrequency catheter ablation. The initial 226 ECGs were analyzed to
      develop a stepwise algorithm, and the subsequent 180 ECGs were prospectively
      evaluated by the new algorithm. RESULTS: The presence of a pseudo r' wave in lead
      V1 or a pseudo S wave in leads II, III, aVF indicated anterior-type AVNRT with an
      accuracy of 100%. With the difference of RP' intervals in leads V1 and III > 20
      ms, posterior-type AVNRT could be differentiated from AVRT utilizing a
      posteroseptal pathway with a sensitivity of 71% (95% confidence interval [CI] 55%
      to 89%), a specificity of 87% (95% CI 67% to 97%) and a positive predictive value
      of 75% (95% CI 56% to 91%). According to the polarity of retrograde P waves in
      leads V1, II, III, aVF and I during AVRT, the concealed accessory pathway could
      be localized to one of the nine regions on the atrioventricular annuli with an
      accuracy of 75% (for a right midseptal pathway) to 93.8% (for a left posterior
      pathway). Overall, the new algorithm had an accuracy of 97.8% in discriminating
      AVNRT from AVRT and 88.1% in localizing a concealed accessory pathway,
      prospectively. Prediction was incorrect in only 15 patients (9.1%). CONCLUSIONS:
      The new ECG algorithm derived from the analysis of retrograde P waves during
      tachycardia could provide a criterion for differential diagnosis between AVNRT
      and AVRT and for predicting the location of concealed accessory pathways.

PMID- 9014996
TI  - Electrophysiologic properties of the atrioventricular node in pediatric patients.
AB  - OBJECTIVES: The purpose of this study was to characterize anterograde and
      retrograde properties of the atrioventricular (AV) node in children and to
      determine the presence of ventriculoatrial (VA) conduction and dual AV node
      pathways. BACKGROUND: Although AV node reentry is common in adults, it accounts
      for 13% of pediatric supraventricular tachycardia (SVT). The age-related changes
      in the AV node with development are poorly understood. The incidence of dual AV
      node pathways and VA conduction in the pediatric population is unknown. METHODS:
      Electrophysiologic studies were performed in 79 patients with normal hearts and
      no evidence of AV node arrhythmias. Patients were classified into two groups by
      age: group I = 49 patients (0.39 to 12.8 years old, mean [+/- SD] age 8.5 +/-
      3.6); group II = 30 patients (13.4 to 20.0 years old, mean age 15.6 +/- 1.8).
      RESULTS: There was a significant difference (p < 0.05) in the cycle length (CL)
      at which anterograde AV block occurred between group I (305 +/- 63 ms) and group
      II (350 +/- 91 ms). Sixty-one percent of children had VA conduction with no age
      related differences. There was no significant difference in the mean CL of
      retrograde VA block (360 ms). The incidence of dual AV node pathways in group I
      was 15% and 44% in group II (p < 0.05). CONCLUSIONS: These findings suggest that
      AV node electrophysiology undergoes maturational changes. The increase in AV node
      reentrant tachycardia in adults may relate to changes in the relative
      refractoriness and conduction of the AV node or to differences in autonomic input
      into the AV node that allow dual pathway physiology to progress to SVT.

PMID- 9014997
TI  - Subthreshold stimulation in the region of the slow pathway during
      atrioventricular node reentrant tachycardia: correlation with effect of
      radiofrequency catheter ablation.
AB  - OBJECTIVES: The present study sought to investigate the role of subthreshold
      stimulation in patients with atrioventricular node reentrant tachycardia (AVNRT)
      undergoing catheter ablation of the slow pathway. BACKGROUND: Subthreshold
      stimulation applied to right atrial sites has been demonstrated to terminate
      AVNRT but has not been correlated with the effects of radiofrequency current
      delivery to the area of the slow pathway. METHODS: Eighteen patients with common
      AVNRT were prospectively included in the study. Sustained AVNRT was reproducibly
      inducible in all patients (cycle length 334 +/- 58 ms). Anatomic and electrogram
      guided mapping of the slow pathway was started posteroseptally and continued to
      more midseptal sites if required. Subthreshold stimulation (3 s, up to 5 mA)
      during induced AVNRT was performed at each site eligible for slow pathway
      ablation until termination of AVNRT or capture was observed. Irrespective of the
      effect of subthreshold stimulation, radiofrequency current was delivered at each
      site after exclusion of catheter dislocation. RESULTS: Termination of AVNRT due
      to block of the anterograde slow pathway induced by subthreshold stimulation
      occurred without apparent capture in 15 of 18 patients. This phenomenon was
      exclusively observed at successful posteroseptal to midseptal ablation sites.
      Subthreshold stimulation was not successful at any of 30 target sites with
      ineffective radiofrequency current delivery. Thus, subthreshold stimulation
      identified successful target sites with 83% sensitivity and 100% specificity.
      Atrioventricular node reentrant tachycardia was abolished in all patients after a
      median of two (range one to nine) radiofrequency current applications.
      CONCLUSIONS: Subthreshold stimulation delivered to the region of the slow pathway
      terminates AVNRT with high safety and efficacy. High sensitivity and specificity
      for prediction of the effect of radiofrequency current application suggest that
      subthreshold stimulation may become a new tool for identifying target sites for
      slow pathway ablation.

PMID- 9014998
TI  - Increased survival after long-term treatment with mibefradil, a selective T
      channel calcium antagonist, in heart failure.
AB  - OBJECTIVES: We sought to investigate the effects of mibefradil on survival,
      hemodynamic variables and cardiac remodeling in a rat model of chronic heart
      failure (HF) and to compare these effects with those of the angiotensin
      converting enzyme (ACE) inhibitor cilazapril. BACKGROUND: The use of calcium
      channel blocking agents in chronic HF has been disappointing. Most studies have
      shown that these drugs have either no or even detrimental effects due in part to
      the negative inotropic effects they induce. Mibefradil is a calcium channel
      blocker that selectively blocks T channels and displays moderately negative
      inotropic properties only at high doses. Because T channels are upregulated in
      the hypertrophied heart and could mediate hypertrophic signals and increase
      arrhythmogenicity, blockade of these channels might be beneficial in chronic HF.
      METHODS: Rats were subjected to coronary artery ligation and 9 months of
      treatment with mibefradil (15 mg/kg body weight per day) or cilazapril (10 mg/kg
      per day) or no treatment. Survival and systolic blood pressure were assessed over
      the 9-month treatment period, after which cardiac hemodynamic variables and
      structure were determined. RESULTS: Mibefradil increased survival rate to the
      same extent as cilazapril (71% for mibefradil vs. 75% for cilazapril and 44% for
      no treatment). Mibefradil decreased systolic blood pressure, although to a lesser
      extent than cilazapril. Both treatments decreased left ventricular (LV) end
      diastolic and central venous pressures, without any change in the first
      derivative of LV pressure over time or heart rate. Mibefradil decreased LV weight
      (although less than cilazapril) without affecting right ventricular weight.
      Finally, both drugs normalized LV collagen density. CONCLUSIONS: Mibefradil in a
      rat model improved survival to the same extent as an ACE inhibitor, without
      impairing LV function, and was associated with a reduction in LV weight and
      fibrosis. Thus, mibefradil might be beneficial in the treatment of chronic HF.

PMID- 9014999
TI  - Prognostic value of noninvasively obtained left ventricular contractile reserve
      in patients with severe heart failure.
AB  - OBJECTIVES: The present study sought to evaluate the prognostic value of
      contractile reserve measured noninvasively during dobutamine infusion in patients
      with severe heart failure. BACKGROUND: In patients with severe heart failure
      there is a great need for objective criteria to define candidates for heart
      transplantation or intensive medical treatment. Cardiac pumping performance
      reserve has been shown to have excellent prognostic value in patients with
      cardiogenic shock. METHODS: Cardiac peak power, an afterload-independent
      contractility index, was measured noninvasively at rest and at peak dobutamine
      inotropic stimulation. Contractile reserve was defined as the difference between
      maximal cardiac power at peak dobutamine dose and baseline value. Maximal cardiac
      power was calculated from the maximal product of validated central arterial
      pressure and aortic flow. RESULTS: Results were obtained from 52 subjects (42
      patients, 10 control subjects). Twenty-two patients were in New York Heart
      Association functional classes III and IV. Of nine patients with a contractile
      reserve < 1.5 W/ml, eight died during the 3-year follow-up period. In contrast,
      all survivors had a contractile reserve > 1.5 W/ml. Using multiple logistic
      regression analysis, contractile reserve was shown to be the only predictor of
      survival. CONCLUSIONS: Contractile reserve measured noninvasively during
      dobutamine infusion is a valuable prognostic indicator in patients with severe
      heart failure, with added value to ejection fraction.

PMID- 9015001
TI  - Dual-chamber pacing for hypertrophic cardiomyopathy: a randomized, double-blind,
      crossover trial.
AB  - OBJECTIVES: In a double-blind, randomized, crossover trial we sought to evaluate
      the effect of dual-chamber pacing in patients with severe symptoms of
      hypertrophic obstructive cardiomyopathy. BACKGROUND: Recently, several cohort
      trials showed that implantation of a dual-chamber pacemaker in patients with
      severely symptomatic hypertrophic obstructive cardiomyopathy can relieve symptoms
      and decrease the severity of the left ventricular outflow tract gradient.
      However, the outcome of dual-chamber pacing has not been compared with that of
      standard therapy in a randomized, double-blind trial. METHODS: Twenty-one
      patients with severely symptomatic hypertrophic obstructive cardiomyopathy were
      entered into this trial after baseline studies consisting of Minnesota quality-of
      life assessment, two-dimensional and Doppler echocardiography and cardiopulmonary
      exercise tests. Nineteen patients completed the protocol and underwent double
      blind randomization to either DDD pacing for 3 months followed by backup AAI
      pacing for 3 months, or the same study arms in reverse order. RESULTS: Left
      ventricular outflow tract gradient decreased significantly to 55 +/- 38 mm Hg
      after DDD pacing compared with the baseline gradient of 76 +/- 61 mm Hg (p <
      0.05) and the gradient of 83 +/- 59 mm Hg after AAI pacing (p < 0.05). Quality-of
      life score and exercise duration were significantly improved from the baseline
      state after the DDD arm but were not significantly different between the DDD arm
      and the backup AAI arm. Peak oxygen consumption did not significantly differ
      among the three periods. Overall, 63% of patients had symptomatic improvement
      during the DDD arm, but 42% also had symptomatic improvement during the AAI
      backup arm. In addition, 31% had no change and 5% had deterioration of symptoms
      during the DDD pacing arm. CONCLUSIONS: Dual-chamber pacing may relieve symptoms
      and decrease gradient in patients with hypertrophic obstructive cardiomyopathy.
      In some patients, however, symptoms do not change or even become worse with dual
      chamber pacing. Subjective symptomatic improvement can also occur from
      implantation of the pacemaker without its hemodynamic benefit, suggesting the
      role of a placebo effect. Long-term follow-up of a large number of patients in
      randomized trials is necessary before dual-chamber pacing can be recommended for
      all patients with severely symptomatic hypertrophic obstructive cardiomyopathy.

PMID- 9015000
TI  - Cell-mediated cytotoxicity in hearts with dilated cardiomyopathy: correlation
      with interstitial fibrosis and foci of activated T lymphocytes.
AB  - OBJECTIVES: The purpose of this study was to investigate the expression of
      perforin and T-cell intracellular antigen-1, two crucial components of lymphocyte
      mediated cytotoxicity, in endomyocardial biopsies from patients with idiopathic
      dilated cardiomyopathy. BACKGROUND: Previous reports have demonstrated the
      presence of myocardial interstitial fibrosis and increased infiltrating
      lymphocytes in patients with dilated cardiomyopathy. However, the pathogenic
      significance of these lymphocytic infiltrates remains unclear. METHODS:
      Endomyocardial biopsies from 134 patients with idiopathic dilated cardiomyopathy
      were histologically and immunohistologically analyzed. Monoclonal antibodies
      against diverse T-lymphocyte antigens, perforin and T-cell intracellular antigen
      1 were used with the highly sensitive avidin-biotin complex technique. Positive
      cells were counted in at least 10 high power field. RESULTS: Perforin and T-cell
      intracellular antigen-1 were immunohistologically detected in all biopsies.
      Immunoreactivity was restricted to the cytoplasm and was granular in nature,
      indicating specific staining of cytoplasmic granules. Correlations were
      established between the expression of perforin and T-cell intracellular antigen-1
      and the abundance of foci of various T-lymphocyte subpopulations and, most
      importantly, the degree of interstitial fibrosis on routine histologic
      examination (p = 0.015). CONCLUSIONS: Cytotoxic activity is clearly present in
      endomyocardial biopsies from patients with idiopathic dilated cardiomyopathy.
      Local activation-that is, focal accumulation of T lymphocytes-seems to be
      important for the generation of lymphocyte-mediated cytotoxicity. The
      interstitial fibrosis commonly seen in dilated cardiomyopathy may be caused by
      cytotoxic T-lymphocyte damage to the myocardium.

PMID- 9015002
TI  - Transvascular balloon dilation for neonatal critical aortic stenosis: early and
      midterm results.
AB  - OBJECTIVES: We evaluated our immediate and midterm (mean 4.3 years) results of
      balloon dilation of critical valvular aortic stenosis in 33 neonates. BACKGROUND:
      Balloon dilation has been used as an alternative to surgical treatment. Reports
      to date consist of small series (largest 16 babies) with short-term follow-up
      (longest 4.8 years). METHODS: From 1985 to 1991, 33 neonates had dilation at a
      mean age of 13 days and a mean weight of 3.4 kg. Nineteen of the neonates (58%)
      were intubated and received prostaglandins, and 94% had other cardiac
      abnormalities. RESULTS: The dilation was completed retrograde in 31 of the
      neonates (umbilical artery in 11 and femoral artery in 20) and anterograde
      (femoral vein) in 2. The average immediate peak gradient and left ventricular end
      diastolic pressure reductions were 54% and 20%, respectively. The overall
      mortality rate was 12% (three early deaths and one late). All 20 neonates dilated
      through a femoral artery initially had pulse loss with restoration in 35% after
      thrombolytic therapy. At 8.3 years, survival and freedom of reintervention
      probability rates were 88% and 64%, respectively. At mean 4.3 years of follow-up,
      83% of the survivors were asymptomatic; Doppler study revealed a maximal
      instantaneous gradient < 50 mm Hg in 65% of neonates and significant aortic
      regurgitation in 14%. CONCLUSIONS: This study confirms that dilation of aortic
      stenosis in neonates is effective; reintervention (mostly redilation) is frequent
      (40%); and midterm survival is encouraging (88%).

PMID- 9015003
TI  - An index of early left ventricular filling that combined with pulsed Doppler peak
      E velocity may estimate capillary wedge pressure.
AB  - OBJECTIVES: This study sought to determine the applicability of the combined
      information obtained from transmitral Doppler flow and color M-mode Doppler flow
      propagation velocities for estimating pulmonary capillary wedge pressure.
      BACKGROUND: Although Doppler-derived measurements of left ventricular (LV)
      filling have been applied to determine left atrial pressure, their accuracy has
      been limited by the variable effect of ventricular relaxation in these indexes.
      Recently, flow propagation velocity measured by color M-mode Doppler
      echocardiography has been suggested as an index of ventricular relaxation.
      METHODS: We studied 45 patients admitted to the intensive care unit who underwent
      invasive hemodynamic monitoring. We measured peak early (E) and late (A)
      transmitral Doppler velocities, E/A ratio and flow propagation velocity (vp) and
      compared them by linear regression with pulmonary capillary wedge pressure (pw).
      RESULTS: We found a modest positive correlation between pw and E (r = 0.62, p <
      0.001) and the E/A ratio (r = 0.52, p < 0.001) and a negative correlation between
      pw and vp (r = -0.34, p = 0.02). By stepwise linear regression, only E and vp
      were statistically significant predictors of pw. However, the E/vp ratio provided
      the best estimate of pw (r = 0.80, p < 0.001; pw = 5.27 x [E/vp] + 4.6, SEE 3.1
      mm Hg). CONCLUSIONS: The ratio of component velocity (E) over the color M-mode
      propagation velocity during early LV filling, by correcting for the effect of LV
      relaxation, provides a better estimate of pw than standard measurements of
      transmitral Doppler flow.

PMID- 9015004
TI  - We've got to stop meeting like this!

PMID- 9015005
TI  - President's page: cardiovascular research--is something missing?

PMID- 9015006
TI  - The American College of Cardiology National Database: progress and challenges.
      American College of Cardiology Database Committee.

PMID- 9015007
TI  - American College of Cardiology report on ECGEXAM.

PMID- 9015008
TI  - Ischemic preconditioning during coronary angioplasty.

PMID- 9015009
TI  - Bradycardia after heart transplantation: reversal with theophylline.

PMID- 9015010
TI  - Clinical value of a new Doppler index in cardiac amyloidosis.

PMID- 9015011
TI  - Digoxin reduces cardiac sympathetic activity in severe congestive heart failure.

PMID- 9015012
TI  - Reimbursement for cardiac rehabilitation services.

PMID- 9015013
TI  - The duration and character of postpartum bleeding among breast-feeding women.
AB  - OBJECTIVE: To examine the postpartum bleeding experience of a cohort of breast
      feeding women and to compare it with the conventional definition of lochia.
      METHODS: Four hundred seventy-seven experienced breast-feeding women in Manila,
      the Philippines, were followed prospectively from delivery and recorded vaginal
      bleeding in a menstrual diary. The median duration of lochia was calculated using
      survival analysis. In addition, all bleeding separate from lochia within the
      first 8 weeks postpartum was noted. RESULTS: The median duration of lochia was 27
      days and did not vary by age, parity, sex or weight of the infant, breast-feeding
      frequency, or level of supplementation. More than one-fourth of the women
      experienced a bleeding episode separated from the original lochial flow by at
      least 4 bleeding-free days and beginning no later than postpartum day 56. Ten
      breast-feeding women may have had their first menstrual bleed before day 56.
      CONCLUSIONS: Lochia lasted substantially longer than the conventional assumption
      of 2 weeks. It was common for postpartum bleeding to stop and start again or to
      be characterized by intermittent spotting or bleeding. Return of menses is rare
      among fully breast-feeding women in the first 8 weeks postpartum.

PMID- 9015014
TI  - Fertility of fully breast-feeding women in the early postpartum period.
AB  - OBJECTIVE: To examine bleeding between 6 and 8 weeks postpartum in fully breast
      feeding women and its association with fertility as assessed by hormone analysis.
      METHODS: Seventy-two fully breast-feeding women were followed prospectively from
      42 days postpartum. Vaginal bleeding was recorded daily. Women who experienced
      bleeding were compared with women who did not with respect to time of ovulation
      and time of first menses. RESULTS: Nearly half of the women experienced some
      vaginal bleeding or spotting between 6 and 8 weeks postpartum. These women
      eventually menstruated and ovulated earlier than the women who did not bleed, but
      the differences were not significant. The study had 34% and 45% power to detect a
      20% difference in the proportion menstruating and ovulating, respectively, at 6
      months postpartum, and 10% and 16% power to detect the same differences at 1
      year. Seven women experienced ovarian follicular development before day 56, but
      neither bleeding nor follicular development was associated with ovulation in any
      woman in the first 8 weeks postpartum. CONCLUSIONS: It is unlikely that vaginal
      bleeding in fully breast-feeding women in the first 8 weeks postpartum represents
      a return to fertility.

PMID- 9015015
TI  - A comparison of "U" and standard techniques for Norplant removal.
AB  - OBJECTIVE: To evaluate the "U" technique versus the manufacturer-recommended
      technique for Norplant removal. METHODS: We conducted a randomized comparison of
      the manufacturer-recommended method of removal and the "U" technique. The latter
      involves an incision between and parallel to the third and fourth implants and
      uses a modified vasectomy clamp to remove the implants by pulling perpendicular
      to the implant's axis. RESULTS: Twenty-one physicians (three experienced, 18
      inexperienced) performed 200 Norplant removals. Inexperienced physicians took
      significantly less time for removal using the "U" technique than the standard
      technique (7.9 versus 10.5 minutes), even after controlling for other factors.
      Experienced physicians also required less time for removal using the "U"
      technique (3.1 versus 3.7 minutes), but the difference was not statistically
      significant after controlling for other factors. Both experienced and
      inexperienced physicians broke implants more frequently using the standard
      technique, although the difference was significant only for experienced
      physicians (relative risk 3.6, 95% confidence interval 1.2, 10.8). No differences
      were noted between the techniques with respect to tissue damage or patient
      reports of pain during or after removal. CONCLUSIONS: These results suggest that
      the "U" technique is an improvement over the standard technique, particularly for
      personnel who are not highly experienced in Norplant removal.

PMID- 9015016
TI  - Training for Norplant implant removal: assessment of learning curves and
      competency.
AB  - OBJECTIVE: To determine the learning curves and rapidity with which clinicians
      become competent in implant removal using two Norplant removal techniques.
      METHODS: Twenty-four physicians, none of whom were experienced in the use of
      Norplant implants, were randomly assigned to learn either the "U" removal
      technique or the standard technique. The physicians in the two groups received
      identical training in all other respects. Each physician then performed ten
      supervised removals. Removal times, procedure problem rates, and the number of
      procedures performed by the clinicians before they were judged "competent" were
      assessed for both groups. RESULTS: Data from 240 removals were analyzed. Mean
      removal times were 38% faster in the "U" group than in the standard group. None
      of the "U" group procedures took longer than 20 minutes, compared with 11% of
      removals in the standard group (P < .001). The mean number of cases required
      before the provider consistently performed all steps adequately was significantly
      (P < .02) higher in the standard group (5.8 cases) than in the "U" group (3.9
      cases). CONCLUSIONS: Using competency-based training methods, the "U" removal
      technique was learned easily by inexperienced clinicians. It appears to offer
      significant improvements in speed and achievement of proficiency over the
      standard technique recommended by the manufacturer. Large-scale programs should
      consider using competency-based training and the "U" technique as the removal
      method of choice when providing training in implant removal.

PMID- 9015017
TI  - Extending the duration of active oral contraceptive pills to manage hormone
      withdrawal symptoms.
AB  - OBJECTIVE: To test the hypothesis that extending the number of consecutive active
      oral contraceptives (OC)s given will decrease the frequency of menstrual-related
      problems including dysmenorrhea, menorrhagia, premenstrual-type symptoms, and
      menstrual migraines. METHODS: A prospective analysis was designed to track the
      experiences of 50 women taking OCs and experiencing menstrual-related problems.
      Fifty consecutive patients, who were taking OCs and had symptoms during the pill
      free interval, were followed in a multispecialty clinic by an individual
      physician and nurse practitioner team. The patients were permitted to extend the
      number of consecutive active OCs to delay menstrual-related symptoms. RESULTS:
      Immediate outcome of the 50 patients revealed 74% (37 patients) stabilized on an
      extended regimen of 6 to 12 weeks of consecutive days with active OCs. Twenty-six
      percent (13 patients) either discontinued OCs or returned to the standard regimen
      with 3 weeks of active pills. Of the 37 patients who were stabilized on an
      extended regimen, 27 have completed thus far between five and 13 extended cycles
      with 6-23 months of follow-up (mean 16 months). CONCLUSIONS: Experience in a
      series of 50 OC users with menstrual-related symptoms demonstrated that delaying
      menses by extending the number of consecutive days of active pills is well
      tolerated and efficacious. We believe that a large prospective study is warranted
      to further our knowledge in this area.

PMID- 9015018
TI  - Acute pelvic inflammatory disease: associations of clinical and laboratory
      findings with laparoscopic findings.
AB  - OBJECTIVE: To assess the relation of clinical variables and laboratory data to
      pelvic laparoscopic observations of tubal occlusion, adnexal adhesions, and
      peritoneal exudate in women with acute salpingitis. METHODS: Clinical and
      laboratory evaluations were performed systematically before laparoscopy in 155
      women with suspected acute pelvic inflammatory disease (PID), 82% of whom proved
      to have acute salpingitis confirmed with laparoscopy. Laparoscopic findings were
      scored in three categories (tubal patency, adhesions, and exudate.) RESULTS: Two
      general categories of laparoscopic findings were present: 1) tubal occlusion and
      moderate to severe adhesions in 30 women, and 2) pelvic-abdominal exudate in 27
      women. In the remaining 16 women, these laparoscopic findings occurred alone or
      in other combinations. Among women with acute salpingitis, tubal occlusion was
      associated positively with older age, palpable adnexal mass, and moderate to
      severe pelvic adhesions; negative associations were found with abdominal rebound
      tenderness, mean abdominal-pelvic tenderness score, pelvic-abdominal exudate, and
      isolation of either Neisseria gonorrhoeae or Chlamydia trachomatis. Moderate or
      severe pelvic adhesions were associated positively with increased duration of
      abdominal pain (5 versus 3 days) compared with limited or no pelvic adhesions,
      but they were associated negatively with mean abdominal-pelvic tenderness score
      and with pelvic-abdominal exudate (47% versus 73%). Free exudate in the pelvis or
      abdomen as compared with limited or no exudate was associated positively with
      abdominal rebound tenderness (86% versus 65%), abdominal-pelvic tenderness score,
      elevated white blood cell count (83% versus 52%), and recovery of N gonorrhoeae
      (79% versus 57%). Free exudate was associated negatively with the median duration
      of pain (3 versus 6 days), oral contraceptive use (4% versus 26%), and palpable
      adnexal mass (7% versus 25%). Analyses limited to women without a history of PID
      gave similar results. CONCLUSIONS: Although clinical and laboratory criteria
      traditionally used to judge the clinical severity of acute PID partially predict
      the degree of tubal or other pelvic abnormalities among women with acute
      salpingitis and tend to distinguish those with tubal occlusion or moderate to
      severe adhesions from those with peritonitis, these criteria have low predictive
      value and are not reliable in the individual patient.

PMID- 9015019
TI  - Quality assessment of perinatal regionalization by multivariate analysis:
      Illinois, 1991-1993.
AB  - OBJECTIVE: To identify (1) those elements in the infrastructure of a regionalized
      perinatal network that have independent effects on the variation in perinatal
      mortality among nontertiary units (member level I and II hospitals) and (2)
      shortcomings, if any, in a traditional perinatal data base that impede quality
      assessment of contemporary regionalized care. METHODS: We analyzed perinatal
      surveillance data for 3 years, from 1991 to 1993, in the state of Illinois,
      representing more than 190,000 annual births. Fetal death and neonatal mortality
      rates for the 97 nontertiary hospitals studied were the dependent variables of
      interest. Two sets of independent variables were studied, those assessing the
      maternal sociobehavioral risk of populations served and those assessing the
      network infrastructure (defined as the facilities of member hospitals and their
      function within the regionalized network). We used multivariate analysis to
      partition the variation in hospital rates of perinatal mortality into two
      components, one attributable to maternal sociobehavioral risk and the other to
      the network infrastructure. RESULTS: Maternal sociobehavioral risk alone
      explained 73% of the variation in hospital fetal death rates and 38% of that in
      hospital neonatal mortality rates. When controlling for maternal sociobehavioral
      risk, rates of inborn very low birth weight (VLBW) deliveries (P < .001) and
      neonatal transport (P = .01) had independent effects on the variation in hospital
      fetal death rate; rates of inborn VLBW deliveries (P < .001), neonatal transport
      (P < .001), and proportion of VLBW infants transported out (P = .029) had
      independent effects on the variation in hospital neonatal mortality rate.
      CONCLUSIONS: In this mature statewide network, the rate of inborn VLBW deliveries
      exerted the strongest independent effect on variation in level I and II hospital
      rates of both fetal death and neonatal mortality. However, that there was such a
      large effect from maternal sociobehavioral risk alone has important public health
      implications. Additions and modifications to traditional perinatal surveillance
      are suggested better to assess the quality of regionalization in a contemporary
      health care environment.

PMID- 9015020
TI  - Risk factors for adult paternity in births to adolescents.
AB  - OBJECTIVE: To examine the risk factors for adult (aged 20 years and older)
      paternity in births to teenagers (14-17 years of age). METHODS: This was a
      population-based, retrospective cohort analysis of 27,215 adolescent mothers
      residing in California who had a live singleton birth during 1993. Adjusted risks
      for adult paternity by paternal and maternal characteristics were derived from
      comparisons of adult-teen and teen-teen couples. RESULTS: Adult fathers, who were
      responsible for 49.2% of births to teenage mothers, were a mean of 6.4 years
      older than the mother. The most important risk factors for adult paternity were
      as follows: father's (odds ratio [OR] 5.19; 95% confidence interval [CI] 4.43,
      6.08) or mother's (OR 1.33; 95% CI 1.14, 1.55) educational attainment of at least
      3 years lower than expected for their age, two or more previous live births (OR
      3.34; 95% CI 2.48, 4.53), mother's birthplace outside the United States (OR 2.33;
      95% CI 2.11, 2.58), father's (OR 2.16; 95% CI 1.98, 2.36) or mother's (OR 1.28;
      95% CI 1.15, 1.42) educational attainment 1-2 years lower than expected for their
      age, one previous live birth (OR 1.92; 95% CI 1.75, 2.12), and Asian (OR 1.29;
      95% CI 1.04, 1.62) or African American race (OR 1.25; 95% CI 1.06, 1.46) of the
      father. CONCLUSIONS: Teenage pregnancy prevention programs must address adult
      paternity, which contributed to almost half of the births in our study. These
      programs should consider education adequacy, cultural beliefs and practices,
      previous live births, and race and ethnicity when designing programs to decrease
      the number of adults involved in teenage births.

PMID- 9015021
TI  - Low pregravid body mass index as a risk factor for preterm birth: variation by
      ethnic group.
AB  - OBJECTIVE: To examine the association between pregravid body mass index (BMI) and
      preterm delivery among black, white, and Hispanic women. METHODS: Preterm
      deliveries among 12,459 women (43.2% black, 39.3% white, and 17.5% Hispanic)
      enrolled in a large multicenter trial of preterm birth prevention were examined
      by pregravid BMI category (very low, less than 16.5; low, 16.5-19.7; normal, 19.8
      26.0; high, greater than 26) and by pathway (all, early, late, spontaneous
      preterm labor, and premature rupture of membranes [PROM]). RESULTS: More than one
      fifth of both black (20.1%) and white (28.6%) women had low pregravid BMIs (less
      than 19.8), whereas only 11.7% of Hispanic women were under-weight. The overall
      prevalence of preterm delivery (gestational age less than 37 completed weeks) was
      8.1% (10.3% in black, 7.3% in white, and 4.8% in Hispanic women). Among black and
      white women, bivariate analysis revealed an inverse linear association between
      pregravid BMI and the prevalence of all preterm deliveries (P < or = .001) and
      between pregravid BMI and the prevalence of late (33-36 weeks' gestation) preterm
      deliveries (P < .001). No such associations were observed for early (20-32 weeks'
      gestation) preterm delivery or among Hispanic women. Pregravid BMI was also
      associated inversely with spontaneous preterm labor among both black (P < or =
      .01) and white (P < .001) women, but not among Hispanic women. Logistic
      regression analysis (adjusting for the effects of maternal age, education,
      smoking, parity, previous preterm delivery, birth interval, and height) revealed
      that among black and white women, very low and low pregravid BMIs were associated
      with increased adjusted odds ratios for late (but not early) preterm delivery and
      for spontaneous preterm labor (but not PROM). CONCLUSIONS: These observations
      suggest that low pregravid BMI is associated with an increase in the prevalence
      of late preterm delivery and of spontaneous preterm labor among black and white,
      but not Hispanic, women.

PMID- 9015022
TI  - Association between pre-pregnancy obesity and the risk of cesarean delivery.
AB  - OBJECTIVE: To explore the relationship between pre-pregnancy obesity and the risk
      for cesarean delivery. METHODS: The population studied included 20,130 women with
      live births after 20 weeks' gestation in central New York state between June 1,
      1994, and May 31, 1995. Women who were obese before pregnancy were compared with
      nonobese women with regard to mode of delivery. Obesity was defined as body mass
      index (BMI) greater than 29. Separate analyses were conducted on the entire
      sample and on a subset of women with singleton pregnancies and no prior cesarean
      deliveries, as an estimate of the risk of primary cesarean delivery in obese
      women. Statistical analyses included chi 2 test, crude odds ratio (OR) with 95%
      confidence interval (CI), and adjusted OR with 95% CI, using logistic regression
      to control for confounding variables. RESULTS: The adjusted OR was 1.64 (95% CI
      1.46, 1.83) for obese women with singleton pregnancies and no prior cesarean
      deliveries to undergo cesarean delivery. The adjusted OR was 1.66 (95% CI 1.51,
      1.82) for obese women in the entire sample to undergo cesarean delivery. In
      addition, increasing BMI was associated with increased risk for cesarean
      delivery. CONCLUSION: Compared with nonobese women, women who are obese before
      pregnancy are at increased risk for cesarean delivery. Preconceptional counseling
      regarding dietary and life-style modifications may alter this pattern.

PMID- 9015023
TI  - Cesarean deliveries: when is a pediatrician necessary?
AB  - OBJECTIVE: We evaluated the need for vigorous resuscitation (bag-and-mask
      ventilation, tracheal intubation, and cardiopulmonary resuscitation) in certain
      common cesarean deliveries at term to evaluate the need for pediatrician
      attendance on behalf of the fetus. METHODS: Records of singleton cesarean
      deliveries (repeat, nonprogressive labor, fetal malposition, fetal heart rate
      abnormality) at term over 2 years were reviewed for the following: need for
      vigorous resuscitation, Apgar scores, anesthesia used, and the need for newborn
      intensive care. The next consecutive, uncomplicated singleton vaginal delivery in
      each case was used to create a control group. Exclusion criteria included the
      presence of maternal disease (diabetes, pregnancy-induced hypertension, placenta
      previa) or suspicion of fetal abnormalities (growth restriction, congenital
      defect, known meconium staining of the amniotic fluid). There were 834 cesarean
      deliveries and 834 controls (low-risk vaginal deliveries). RESULTS: Compared with
      vaginal deliveries, Apgar scores of 6 or less at 1 minute were more frequent in
      all cesarean deliveries except for the repeat cesarean category. The incidence of
      needing vigorous resuscitation was as follows: vaginal 1.7%, repeat 3.0%,
      nonprogressive labor 4.8%, fetal malposition 11.2%, and fetal heart rate
      abnormality 17.7%. The use of regional anesthesia reduced the need for vigorous
      resuscitation in cesarean deliveries for the repeat group and the group with
      nonprogressive labor without fetal heart rate abnormalities to a level similar to
      that in uncomplicated vaginal deliveries (2.1% repeat; 1.6% nonprogressive labor
      without fetal heart rate abnormality). CONCLUSIONS: Both repeat cesarean
      deliveries and cesareans done for nonprogressive labor without signs of fetal
      heart rate abnormality, when performed under regional anesthesia, may not need a
      pediatrician in attendance because of minimal fetal risk.

PMID- 9015024
TI  - Etiologic determinants of abruptio placentae.
AB  - OBJECTIVE: To quantify the roles of suspected sociodemographic, anthropometric,
      behavioral, and pathologic determinants in the etiology of abruptio placentae.
      METHODS: We performed a hospital-based cohort study of 36,875 nonreferred births
      between January 1978 and March 1989. Gestational age was based on menstrual dates
      confirmed (within 7 days) by early ultrasound. RESULTS: Parity, maternal
      education, pre-pregnancy weight, and the rate of net gestational weight gain did
      not have significant independent associations with abruption. Significant
      determinants included the following: severe small for gestational-age (SGA) birth
      (odds ratio [OR] 3.99; 95% confidence interval [CI] 2.75, 5.77), chorioamnionitis
      (OR 2.50; 95% CI 1.58, 3.98), prolonged rupture of membranes (OR 2.38; 95% CI
      1.55, 3.65), preeclampsia (OR 2.05; 95% CI 1.39, 3.04), pregnancy-induced
      hypertension without albuminuria (OR 1.57; 95% CI 1.00, 2.46), pre-pregnancy
      hypertension (OR 1.77; 95% CI 1.05, 2.99), maternal age at least 35 years (OR
      1.50; 95% CI 1.14, 2.01), unmarried status (OR 1.50; 95% CI 1.13, 1.98),
      cigarette smoking (OR 1.40; 95% CI 1.00, 1.97 for ten to 19 cigarettes per day
      and OR 1.13; 95% CI 0.81, 1.59 for at least 20 cigarettes per day), and male
      fetal gender (OR 1.38; 95% CI 1.12, 1.70). Removal of SGA from the regression
      model resulted in little change in the magnitude of the other associations.
      CONCLUSIONS: Severe fetal growth restriction, prolonged rupture of membranes,
      chorioamnionitis, hypertension (before pregnancy and pregnancy-induced),
      cigarette smoking, advanced maternal age, unmarried status, and male fetal gender
      are significant etiologic determinants of placental abruption. Non-SGA
      determinants appear to operate largely independently of their effects on fetal
      growth.

PMID- 9015025
TI  - Sonographic screening to detect fetal cardiac anomalies: a 5-year experience with
      111 abnormal cases.
AB  - OBJECTIVE: To determine whether there is a difference between the types of
      cardiac lesions detected as abnormal prenatally and those that are not detected.
      METHODS: Consecutive fetuses at 14 weeks' gestation or more were scanned in our
      unit from February 1990 through July 1995 and later were delivered at our
      hospital. Outcome information was obtained from neonatal echocardiograms and
      autopsies. Our results were compared to sensitivities for individual cardiac
      lesions based on pooled data from studies published previously. RESULTS: There
      were 111 fetuses with cardiac anomalies, of which 73 (66%) were identified
      correctly as abnormal prenatally. Sensitivities for the most common cardiac
      lesions were as follows: 87% atrioventricular septal (endocardial cushion)
      defects, 65% tetralogy of Fallot, 63% transposition of the great arteries, 50%
      aortic coarctation, and 44% isolated ventricular septal defects. The lesions that
      went undetected most frequently were isolated septal defects (n = 17); most of
      these were ventricular and small or moderate in size. Based on our sensitivities
      and those calculated from previous studies, the fetal cardiac lesions with the
      highest detection rates involve hypoplastic ventricles and atrioventricular
      septal defects, followed by lesions of the great arteries and finally by isolated
      septal defects. CONCLUSIONS: The sensitivity of sonographic screening to defect
      fetal cardiac anomalies varies with the type of lesion. Isolated septal defects
      are the most difficult lesions to detect.

PMID- 9015026
TI  - Cerebral lateral ventricular asymmetry: is this a normal ultrasonographic finding
      in the fetal brain?
AB  - OBJECTIVE: To evaluate the clinical significance of in utero detection of fetal
      cerebral lateral ventricular asymmetry. METHODS: We used high resolution
      ultrasonography to study asymmetries of the fetal lateral ventricles in the human
      brain. A retrospective survey was conducted on 7200 pregnant women who presented
      at two large district hospitals in Israel. Only fetuses with a difference of
      greater than 2.4 mm (two standard deviations) in the width of the lateral
      ventricles, with no known brain pathology, were included in the study. Index
      cases were evaluated regarding maternal complications, prenatal ultrasound
      examinations, postnatal imaging studies, and neonatal outcome up to 6 months of
      age. RESULTS: Lateral ventricular asymmetry was found in 21 subjects, all with
      available clinical data. In 15 fetuses (71%), the body or the occipital horn of
      the left lateral ventricle was larger than the right, whereas in six fetuses
      (29%), the right was larger than the left. In four cases (20%), serial scans
      noted resolution of asymmetry; in 15 (75%), it was persistent; and in one (5%),
      asymmetry increased. In one case, termination of pregnancy was performed;
      however, pathologic examination of the fetal brain failed to detect any
      structural abnormality. Underlying cerebral pathology was later found only in
      three fetuses (14%); one had subclinical cytomegalovirus ventriculitis, one had
      insidious periventricular hemorrhage, and in one fetus with increased asymmetry,
      trisomy 21 was verified. All the remaining 17 cases had normal neurologic
      development. CONCLUSIONS: Some degree of asymmetry of the lateral ventricles
      exists in the human fetal brain and is detectable in utero. Lateral ventricular
      asymmetry alone is probably not clinically significant, and it may be considered
      as a normal variant, rather than a pathologic finding.

PMID- 9015027
TI  - Morphometric study of the placental vessels and its correlation with umbilical
      artery Doppler flow.
AB  - OBJECTIVE: To determine the changes in the vessel-wall thickness and the radius
      of the lumen in tertiary-stem villi of the placenta with advancing gestational
      duration and their relationship to umbilical artery Doppler flow studies.
      METHODS: Placentas from 63 miscarriages and preterm and term deliveries (between
      19 and 40 weeks) were used for morphometric study of the tertiary-stem villi
      vessels. Each woman had undergone Doppler flow study of the umbilical artery. The
      resistance index (RI) was determined from the Doppler flow velocity waveform.
      Placental paraffin sections of 4-micron thickness were stained with hematoxylin
      and eosin and with periodic acid-Schiff reagents. The tertiary-stem villi and
      their vessels were examined microscopically and assessed morphometrically using a
      personal computer with math co-processor and a touch-sensitive screen overlying a
      video monitor. The monitor received microscopic images from a video camera that
      was mounted on a microscope. We determined vessel-wall thickness by tracing the
      outer and inner circumferences of digitized vessel-wall images. RESULTS: Wall
      thickness, but not lumen size, of the tertiary-stem villi vessels decreased
      significantly overall at a rate of 0.63micron/week (P < .001). The rate of
      decrease was 0.64micron/week (P < .001) during the second trimester and
      0.50micron/week (P < .001) during the third trimester. There was a significant
      correlation between the decrease in thickness and in RI (r = 0.83 [P < .001], r =
      0.78 [P < .001] in the second and third trimesters, respectively). Resistance
      indices were all within normal limits. CONCLUSIONS: Placental tertiary-stem villi
      vessel-wall thickness decreases with advancing gestational age. There is a
      correlation between the changes in RI of the umbilical artery Doppler flow and
      the changes in mean wall thickness of the placental vessels.

PMID- 9015028
TI  - Atrial natriuretic peptide levels in fetal blood in relation to inferior vena
      cava velocity waveforms.
AB  - OBJECTIVE: To determine whether blood levels of atrial natriuretic peptide in
      small for gestational age (SGA) fetuses are related to Doppler indices measured
      in arterial and venous vessels. METHODS: Atrial natriuretic peptide was assayed
      in fetal blood obtained at funipuncture in 42 third-trimester fetuses, of whom 11
      were appropriate for gestational age (AGA) and 31 were SGA. Small for gestational
      age fetuses were divided into three groups according to Doppler findings in the
      umbilical artery and inferior vena cava: 1) normal in both vessels (n = 10); 2)
      abnormal in the umbilical artery but normal in the inferior vena cava (n = 10);
      and 3) abnormal in both vessels (n = 11). Atrial natriuretic peptide levels were
      related to Doppler indices and acid-base status of the fetal blood. RESULTS:
      Small for gestational age fetuses with abnormal waveforms in both vessels had
      higher atrial natriuretic peptide blood levels (median 544.8 pg/mL, range 404.2
      1112.3) compared with AGA fetuses (median 316.8 pg/mL, range 159.3-470.1; P < or
      = .001), SGA fetuses with normal waveforms only in both vessels (median 299.8
      pg/mL, range 242.6-480.5; P < or = .001), and SGA fetuses with abnormal waveforms
      only in the umbilical artery (median 367.6 pg/mL, range 192.7-748.9; P = .002).
      Blood levels of atrial natriuretic peptide were significantly related to the
      preload index in the inferior vena cava (p = 0.554, P < or = .001). This relation
      remained significant when the analysis was restricted to the SGA fetuses with
      abnormal waveforms in the umbilical artery and the inferior vena cava (p = 0.673,
      P = .03). CONCLUSIONS: Small for gestational age fetuses with abnormal velocity
      waveforms in the inferior vena cava have significantly higher concentrations of
      atrial natriuretic peptide. This may represent a compensatory mechanism in the
      SGA fetus for regulation of an abnormal hemodynamic condition.

PMID- 9015029
TI  - Aneuploidy in twin gestations: when is maternal age advanced?
AB  - OBJECTIVE: To determine the maternal age at which twin gestations have a risk of
      fetal aneuploidy comparable to that of singleton pregnancies at maternal age 35,
      accounting for variation in dizygotic twinning rates by maternal age and race.
      METHODS: Known aneuploidy risks and rates of dizygotic twinning by maternal age
      and race were used to calculate the risk of fetal aneuploidy at term and in the
      second trimester by maternal age and race in twin gestations, using previously
      published calculations. RESULTS: The risk of at least one aneuploid twin at term
      is 1/193 at maternal age 31 for both white and African-American women, which is
      comparable to the risk of 1/192 for an aneuploid singleton term pregnancy at
      maternal age 35. The risk of at least one aneuploid twin at amniocentesis at
      maternal age 31 is 1/190 for white and 1/187 for African-American women, which is
      slightly lower than the rate in singletons of 1/135. CONCLUSION: Invasive
      prenatal diagnosis for detection of fetal aneuploidy should be offered to all
      women with twin gestations at age 31, regardless of race.

PMID- 9015030
TI  - Doppler assessment of the intervillous blood flow in normal and abnormal early
      pregnancy.
AB  - OBJECTIVE: To compare resistance index (RI) and pulsatility index (PI) in the
      spiral and intervillous arteries, and peak systolic velocity of the continuous
      intervillous flow in normal and abnormal first-trimester pregnancy. METHODS:
      Transvaginal color and pulsed Doppler were used in a prospective analysis of 60
      normal (controls) and 54 abnormal (30 missed abortions and 24 anembryonic)
      pregnancies (6-12 weeks' gestation). Repeated-measures analysis of variance was
      used for comparison between groups. RESULTS: A gradual decrease in spiral artery
      RI and PI was found in women with anembryonic pregnancies. No difference in
      spiral artery impedance was noted in women with normal pregnancies, but there was
      a progressive increase in spiral artery RI and PI in women with missed abortion.
      A significant increase in continuous intervillous blood flow velocity was noted
      from the 11th week onward in the normal pregnancy group (8.0 +/- 0.9 versus 12.2
      +/- 1.4 cm/second). Intervillous arterial blood flow signals did not demonstrate
      any difference in RI and PI with advancing gestational duration. Significantly
      lower PI values were obtained from the intervillous arteries in women with
      anembryonic pregnancy (PI 0.54 +/- 0.04) than in controls (PI 0.80 +/- 0.04) and
      those with missed abortions (PI 0.75 +/- 0.04). However, there was no
      statistically significant difference in the intervillous RI between subgroups.
      CONCLUSION: The new generation of sensitive Doppler units can detect intervillous
      flow as a continuous progressive process during the first trimester of normal and
      abnormal pregnancy. There is a significant difference in intervillous artery
      vascular impedance between normal and anembryonic pregnancies.

PMID- 9015031
TI  - Group B streptococcus colonization in pregnant diabetic women.
AB  - OBJECTIVE: To evaluate the influence of maternal diabetes on the risk of group B
      streptococcus colonization during pregnancy. METHODS: We prospectively analyzed
      data on 105 pregnant women with diabetes mellitus, both pregestational and
      gestational, and a control group of 300 pregnant women without carbohydrate
      intolerance. All had singleton gestations, negative tests for human
      immunodeficiency virus, and intact membranes at enrollment. Culture specimens for
      group B streptococcus were obtained from the lower vaginal walls and rectum. Two
      tailed unpaired Student t test, Mann-Whitney U test, and chi 2 test were used as
      appropriate. Multiple logistic regression analyses were performed to evaluate the
      independent influence of maternal diabetes on the rate of group B streptococcus
      colonization. RESULTS: Compared to controls, diabetic women had a higher
      colonization rate (43.8 versus 22.7%, odds ratio [OR] 2.56, 95% confidence
      interval [CI] 1.6, 4.1). The prevalence of group B streptococcus colonization in
      pregestational diabetic women was 54.1% and in women with gestational diabetes it
      was 35.1% (P = .05). Among women with pregestational diabetes, the prevalence of
      group B streptococcus colonization was 59.1% in class B and 50.0% in class C to R
      (P = not significant). After we adjusted for maternal age, race, and obesity,
      diabetic women continued to be at increased risk of group B streptococcus
      colonization (OR 3.1, 95% CI 1.8, 5.2). CONCLUSION: Carbohydrate intolerance
      appears to be an independent risk factor for group B streptococcus colonization
      during pregnancy.

PMID- 9015032
TI  - Vaginal fluid hCG levels for detecting premature rupture of membranes.
AB  - OBJECTIVE: To determine if the measurement of hCG levels in vaginal fluid is
      useful for the diagnosis of premature rupture of membranes (PROM). METHODS: After
      irrigating the posterior vaginal fornix with 3 mL of sterile saline and procuring
      vaginal washings, we measured hCG levels. Samples were analyzed from 188 normal
      pregnant women, 42, 61, and 85 during the first, second, and third trimesters,
      respectively. Levels of hCG were compared with those of 24 women with confirmed
      PROM. RESULTS: The median and 95% confidence intervals (CIs) of vaginal fluid hCG
      levels of normal pregnant women were 37.9 (1.9, 725.6), 9.5 (0.8, 95.8), and 6.3
      (0.6, 62.2) mIU/mL during the first, second, and third trimesters, respectively.
      That of women with PROM was 420.6 (216.3, 918.3) mIU/mL. For the second
      trimester, sensitivity was 100%, specificity 91.8%, positive predictive value
      82.8%, negative predictive value 100%, and accuracy 94.1%; and for the third
      trimester, sensitivity was 100%, specificity 96.5%, positive predictive value
      88.9%, negative predictive value 100%, and accuracy 97.2%, using a threshold
      value of 50 mIU/mL. CONCLUSION: The hCG level in vaginal fluid is a useful marker
      of PROM during the second and third trimesters.

PMID- 9015033
TI  - Placental histology and clinical characteristics of patients with preterm
      premature rupture of membranes.
AB  - OBJECTIVE: To analyze the placental histology in cases of preterm premature
      rupture of membranes (PROM), classify the cases according to the results of the
      histologic examination, and determine if these histologic groups have different
      clinical characteristics and outcomes. METHODS: During a 3-year period, a cohort
      of 235 women with preterm PROM was studied prospectively. The women were
      classified according to placental histologic findings, and their prenatal and
      intrapartum courses and perinatal mortality and morbidity were analyzed and
      compared. RESULTS: One hundred two placentas (43.4%) exhibited acute inflammatory
      lesions, 48 (20.4%) had vascular lesions, 48 (20.4%) had both inflammatory and
      vascular lesions, 31 (13.2%) had no abnormal findings, four (1.7%) had villous
      edema, and two (0.8%) had chronic villitis. The four largest histologic groups
      had distinctive characteristics with respect to gestational age at the time of
      PROM and at delivery, duration of the latency period, and perinatal mortality and
      morbidity. CONCLUSION: Cases of preterm PROM may be classified according to
      placental histologic findings, and these groups have different clinical
      manifestations, prognoses, and outcomes.

PMID- 9015034
TI  - Female alloimmunization with antibodies known to cause hemolytic disease.
AB  - OBJECTIVE: To determine the current frequency of red blood cell antigen
      alloimmunizations that are capable of causing hemolytic disease and would be
      suitable for prenatal DNA studies. METHODS: We reviewed blood-bank records at a
      single large tertiary center to identify patients with a positive antibody screen
      between January 1993 and June 1995. Data were analyzed based on age, gender, and
      specific blood-group alloimmunizations. The incidence of antibodies as published
      in the literature was reviewed and compared with our data. RESULTS: We identified
      452 women who had a positive antibody screen. The frequencies of specific
      alloimmunization relevant to the development of fetal hemolytic disease were:
      anti-D, 18.4%; anti-E, 14%; anti-c, 5.8%; anti-C, 4.7%; Kell group, 22%; anti
      MNS, 4.7%; anti-Fya (Duffy), 5.4%; and anti-Jka, 1.5%. Compared with other
      populations, in our group the frequency of antibodies to RhD decreased and Kell
      alloimmunization increased between 1967 and 1996. CONCLUSIONS: Despite the use of
      rhesus immune globulin, anti-D is still a common antibody identified in women
      presenting to a tertiary care center. The frequency of the Kell-group
      alloimmunization is higher among the central New York female population than in
      other populations. Rhesus and Kell antigen status can be determined by DNA
      studies. Research in prenatal determination of fetal antigen status should
      continue, as alloimmunization to these antigens is common.

PMID- 9015035
TI  - A comparison of the bioavailability of oral and intramuscular dexamethasone in
      women in late pregnancy.
AB  - OBJECTIVE: To compare the bioavailability of oral and intramuscular (i.m.)
      dexamethasone in third-trimester pregnant women. METHODS: Oral and i.m.
      dexamethasone levels were compared in a randomized, parallel, crossover
      bioavailability study involving 11 gravid women in the third trimester of
      pregnancy. Subjects were randomized to receive either 6 mg of i.m. or 8 mg of
      oral dexamethasone. The following week, the alternative regimen was administered.
      Serial blood samples were obtained after drug administration. Dexamethasone
      concentrations were measured by radioimmunoassay. Total area under the curve was
      compared for the oral and i.m. groups using a paired t test. RESULTS: Eight of
      the 11 women completed the study through 12 hours; all 11 women completed the
      study through 6 hours. Among the 11 women, peak levels of dexamethasone occurred
      30 minutes after i.m. injection (mean +/- standard deviation, 101.7 +/- 19.2
      ng/mL) and 120 minutes after oral administration (65.9 +/- 20.5 ng/mL). Area
      under the curve did not differ significantly between those receiving i.m.
      dexamethasone (258.3 +/- 50.0 ng/minute/mL) and those receiving oral
      dexamethasone (251.8 +/- 59.7 ng/minute/mL) when measured 6 hours after
      administration of the drug. Terminal half-lives were similar in the i.m. and oral
      groups. Similar findings were noted among the eight women who were studied
      through 12 hours. This study had a power of 87% to detect a 20% difference in
      area under the curve between the two groups. CONCLUSION: The bioavailability of 8
      mg of oral dexamethasone is similar to that of a 6-mg IM dose, as determined by
      the area under the curve.

PMID- 9015036
TI  - Vacuum extraction: does duration predict scalp injury?
AB  - OBJECTIVE: To identify variables that increase the chance of neonatal scalp
      injury during vacuum extraction. METHODS: We conducted a prospective
      observational study of 134 vacuum extraction-assisted deliveries at Olive View
      UCLA Medical Center in 1995. Data collected included parity, gestational age,
      duration of first and second stages of labor, indication for operative delivery,
      station and position of fetal head, duration of vacuum application, number of
      "pop-offs," neonatal weight, and descriptions of scalp marks or injury. Cranial
      imaging studies were obtained if clinically indicated. RESULTS: There were 28
      infants with scalp trauma, including 17 superficial lacerations, six large
      caputs, and 12 cephalohematomata; one infant had subgaleal, subdural, and
      subarachnoid hemorrhages. Logistic regression analysis showed duration of vacuum
      application to be the best predictor of scalp injury, followed by duration of
      second stage of labor and paramedian cup placement. Duration of vacuum
      application ranged from 0.5 to 26 minutes, with a median length of 3 minutes. The
      proportion of injuries was greater for applications exceeding 10 minutes (6 of 9)
      than for those 10 minutes or shorter (22 of 121, P < .01). We did not encounter
      any cases of clinically important scalp injury. CONCLUSIONS: Cosmetic scalp
      trauma occurred in 21% of our newborns delivered by vacuum extraction and was
      more common after longer vacuum applications, longer second stages, and
      paramedian cup placement.

PMID- 9015037
TI  - Antitumor effects of internal iliac arterial infusion of platinum compounds in a
      rabbit cervical cancer model.
AB  - OBJECTIVE: To compare three platinum compounds for their antitumor effects on
      cervical cancer after systemic and intra-arterial infusion. METHODS: Adult female
      rabbits with squamous cell carcinoma of the uterine cervix received infusions of
      1.7 mg/kg cisplatin, 10 mg/kg carboplatin, or 6 mg/kg cis-diammine
      (glycolato)platinum (254-S) via the internal iliac artery or ear vein. Platinum
      concentrations in the tumor and tumor size were measured after internal iliac
      arterial or intravenous (i.v.) infusion with these platinum compounds. RESULTS:
      The platinum concentration in the tumor after intra-arterial infusion was
      significantly higher than that after i.v. infusion for cisplatin. However, the
      tumor concentrations of platinum for carboplatin and 254-S did not differ between
      the infusion methods. The platinum concentration 20 minutes after i.v. infusion
      was significantly higher for 254-S than for cisplatin or carboplatin. The
      platinum concentration 7 days after intra-arterial infusion was significantly
      higher with cisplatin than with carboplatin or 254-S. Tumor size 7 days after
      intra-arterial infusion was significantly smaller than that after i.v. infusion
      for cisplatin (1.85 +/- 0.54 versus 5.60 +/- 2.60 cm2; P < .05). Tumor size was
      significantly smaller with 254-S than with cisplatin or carboplatin using the
      i.v. infusion method (2.40 +/- 0.21 cm2 for 254-S, 5.60 +/- 2.60 cm2 for
      cisplatin, and 5.13 +/- 1.59 cm2 for carboplatin, P < .05. CONCLUSIONS: Intra
      arterial infusion seems to be a suitable route of administration for cisplatin,
      whereas i.v. infusion appears to have an advantage for 254-S in the treatment of
      cervical cancer.

PMID- 9015038
TI  - Elevated tissue levels of interleukin-1 beta and tumor necrosis factor-alpha in
      vulvar vestibulitis.
AB  - OBJECTIVE: To compare levels of two inflammatory cytokines, interleukin-1 beta(IL
      1 beta) and tumor necrosis factor-alpha(TNF-alpha), in selected regions of the
      vulva, vestibule, and vagina in women with vulvar vestibulitis and in
      asymptomatic controls. METHODS: Selective samplings of surgical specimens from 12
      women undergoing perineoplasty for vulvar vestibulitis and ten pain-free subjects
      undergoing posterior vaginal repair were prepared into tissue homogenates and
      analyzed for concentrations of IL-1 beta and TNF-alpha. Interleukin-1 beta and
      TNF-alpha concentrations were measured by sandwich enzyme-linked immunosorbent
      assay. The results were reported after adjustment for total tissue protein
      concentration. RESULTS: Median tissue levels of IL-1 beta and TNF-alpha were
      elevated 2.3-fold and 1.8-fold, respectively, in women with vulvar vestibulitis
      relative to pain-free women. Median IL-1 beta tissue levels were increased
      significantly from 1.3 pg/mg to 3.0 pg/mg total protein in women with vulvar
      vestibulitis compared to pain-free women. Median TNF-alpha tissue levels were
      increased from 83 pg/mg to 148 pg/mg total protein in women with vulvar
      vestibulitis compared to pain-free women. Analysis by selected anatomic site of
      women with vulvar vestibulitis revealed a significant 2.2-fold higher median
      level of TNF alpha at the vulvar site compared to the vestibule. CONCLUSION:
      Concentrations of IL-1 beta and TNF-alpha were elevated in women with vulvar
      vestibulitis relative to those in asymptomatic controls. This elevation in
      inflammatory cytokines with vulvar vestibulitis varied according to anatomic site
      and was, paradoxically, lowest in the area of highest hyperalgesia, the vulvar
      vestibule. Inflammatory cytokine elevation may contribute to the pathophysiology
      of mucocutaneous hyperalgesia.

PMID- 9015039
TI  - Short-term effects of topical testosterone in vulvar lichen sclerosus.
AB  - OBJECTIVE: To evaluate the systemic and therapeutic effect of topical
      testosterone treatment in vulvar lichen sclerosus. METHODS: This prospective
      clinical, single-arm study included ten postmenopausal women with vulvar lichen
      sclerosus. Testosterone propionate (0.04 g daily) was administered topically for
      4 weeks. Serum androgens (testosterone, free testosterone, androstenedione,
      dehydroepiandrosterone sulfate) were determined before and after 4 weeks of
      treatment, and vulvodynia was evaluated by a horizontal visual analogue scale.
      RESULTS: Serum levels of total testosterone increased in all patients (P < .01)
      and exceeded normal range in eight of ten women. Vulvodynia improved in nine of
      ten patients (paired t test: P < .01). Four of ten patients showed clinical signs
      of hyperandrogenism (enlargement of the clitoris, alterations of the voice,
      increase in libido) after 4 weeks of treatment. The only patient without
      subjective improvement had elevated basal serum androgen levels and showed
      clinical signs of hyperandrogenism before therapy. CONCLUSION: Topical
      testosterone is effective in normoandrogenic women with lichen sclerosus.
      Androgen status should be evaluated before treatment, and dosage should be
      individualized to avoid virilization and metabolic side effects. Because there is
      a marked systemic effect, clinical controls and a follow-up with evaluation of
      serum testosterone levels are recommended. Other steroids should be included in
      therapeutic decisions.

PMID- 9015040
TI  - Storage of newborn stem cells for future use.
AB  - Human placental cord blood contains a large number of hematopoietic progenitor
      cells, which could be used as a source of stem cells for the treatment of
      hematologic disorders and malignancies. Advantages of cord blood use include
      noninvasive collection, low risk for viral infection, and immunologic naivete.
      Cord blood may be used as stem-cell rescue in all applications of bone marrow
      transplantation, including gene therapy. Given this potential utility, questions
      are raised regarding the regulation of cord-blood collection, storage, and use.
      Should the prospective parent(s) donate the infant's cord blood for treatment of
      unrelated recipients, or should they invest in cord-blood storage as biologic
      "life insurance" for the child's later use? This issue presents many conflicts
      for families and their health care providers.

PMID- 9015041
TI  - Complications and recovery from laparoscopy-assisted vaginal hysterectomy
      compared with abdominal and vaginal hysterectomy.
AB  - OBJECTIVE: To complete a systematic review of the published literature comparing
      complications, postoperative recovery time, and costs following laparoscopy
      assisted vaginal hysterectomy, total abdominal hysterectomy (TAH), and vaginal
      hysterectomy. DATA SOURCES: We searched MEDLINE and several bibliographies,
      identifying all reports using the term "laparoscopy-assisted hysterectomy"
      published from 1989 to September 1995. METHODS OF STUDY SELECTION: We excluded
      case reports, letters, and reports of laparoscopy-assisted vaginal hysterectomy
      procedures used for radical cancer surgery, sex-change operations, total
      laparoscopic hysterectomy, or supracervical hysterectomy. TABULATION,
      INTEGRATION, AND RESULTS: Cases identified included 3112 laparoscopy-assisted
      vaginal hysterectomies, 1618 TAHs, and 690 vaginal hysterectomies. Laparoscopy
      assisted vaginal hysterectomy cases compared with TAH cases demonstrated
      significantly greater incidence of bladder injury (1.8% for laparoscopy-assisted
      vaginal hysterectomy versus 0.4% for TAH; P = .01), significantly longer
      operating room time (115 minutes, standard deviation [SD] 37 minutes, for
      laparoscopy-assisted vaginal hysterectomy versus 87 minutes, SD 18 minutes, for
      TAH; P < .001), and significantly shorter hospitalization (49 hours, SD 16 hours,
      for laparoscopy-assisted vaginal hysterectomy versus 79 hours, SD 20 hours, for
      TAH; P < .001). Use of analgesia was consistently less for laparoscopy-assisted
      vaginal hysterectomy and return to full activity was always sooner when compared
      to TAH. Cost for the new procedure was higher in seven out of 11 studies, but
      when disposable instruments and hospital length of stay are considered, the
      remaining four studies reported a lower cost for laparoscopy-assisted vaginal
      hysterectomy. CONCLUSION: Although laparoscopy-assisted vaginal hysterectomy
      involves a shorter hospital stay, speedier postoperative recovery, and less
      analgesia use, there is also a higher rate of bladder injury and lengthier
      surgery. These outcomes must be weighed when choosing an intervention.

PMID- 9015042
TI  - Anterior vaginal prolapse: review of anatomy and techniques of surgical repair.
AB  - OBJECTIVE: To summarize the literature on anterior vaginal prolapse, focusing on
      vaginal anatomy, etiologic theories, and comparison of anterior colporrhaphy and
      paravaginal repair. DATA SOURCES: We identified articles related to anterior
      vaginal prolapse through a MEDLINE search of English-language literature
      published from January 1966 through December 1995 and in bibliographies in
      gynecologic textbooks. METHODS OF STUDY SELECTION: We reviewed 80 articles
      published in peer-reviewed journals or textbooks and related to anterior vaginal
      prolapse. In addition, ten articles on operative procedures for urinary
      incontinence were studied. TABULATION, INTEGRATION, AND RESULTS: We abstracted
      and synthesized information from 31 papers that contained descriptions of and
      opinions on vaginal anatomy and etiology of vaginal prolapse. The vagina has
      three layers-mucosa, muscularis, and adventitia; there is no vaginal "fascia."
      Vaginal support is provided by the underlying levator ani muscles and by lateral
      connective-tissue attachments at the arcus tendineus fasciae pelvis or "white
      line." Anterior vaginal prolapse results from direct or indirect damage to the
      pelvic muscles or connective tissue or both. Forty-nine articles described
      surgical techniques for the correction of anterior vaginal prolapse, and 24 of
      them reported postoperative outcomes. Reported failure rates ranged from 0-20%
      for anterior colporrhaphy and 3-14% for paravaginal repair. No controlled studies
      compared different procedures performed primarily for correction of anterior
      vaginal prolapse. CONCLUSIONS: Dissection during anterior colporrhaphy splits
      vaginal muscularis, and repair involves plication of the muscularis and
      adventitia (not vaginal "fascia") in the midline, which may pull the lateral
      attachments further from the pelvic sidewall. Paravaginal repair restores the
      lateral attachments to the pelvic sidewall at the white line. Controlled studies
      that compare directly these two procedures for anterior vaginal prolapse repair
      are necessary to determine their relative effectiveness.

PMID- 9015043
TI  - Skull fracture caused by vacuum extraction.

PMID- 9015044
TI  - The risk of carbon monoxide poisoning after prolonged laparoscopic surgery.

PMID- 9015045
TI  - Stanley Baum, MD: a humanistic work in progress.

PMID- 9015046
TI  - Radiologic assessment of renal masses: implications for patient care.
AB  - The relationships between the gross pathologic features of neoplastic and
      nonneoplastic renal masses and their radiologic analogues, described above,
      establish specific guidelines for the influence of radiologic studies on clinical
      management. A tumor that contains fat, as determined with CT or MR imaging, can
      be confidently diagnosed as an angiomyolipoma without further diagnostic
      intervention. The size of the lesion should be used to influence clinical
      decisions related to the fact that angiomyolipomas larger than 4 cm in diameter
      are more apt to hemorrhage than those smaller than that size. High confidence can
      also be assigned to those renal masses that exhibit the radiologic analogues for
      hemangioma with use of imaging modalities that document their vascular nature.
      These findings should be sufficient for therapeutic decisions directed toward
      embolization or surgical excision when clinically warranted. If a mass can be
      characterized as a simple cyst by satisfying all of the required CT or
      sonographic criteria, no further diagnostic interventions are required. This
      includes the radiologic findings of thin rim of peripheral calcification and thin
      septa with or without calcification. An equally high level of confidence is
      associated with the broad range of CT, sonographic, or MR imaging findings that
      indicate malignant tumor. These militate for radical surgery. However, the same
      findings are also encountered in hemorrhagic and infected renal cyst, abscess,
      benign neoplasms, and inflammatory mass. Therefore, surgical excision, the nature
      of which will vary according to individual circumstances, is usually required to
      establish these diagnoses. Exceptions to the need for a tissue diagnosis might be
      considered in the patient in whom a renal mass is detected in the clinical
      setting of infection and in the patient with either a small asymptomatic renal
      mass or a small hyperattenuating mass that meets the other criteria of a simple
      cyst. Here again, individual circumstances may lead to such alternatives as
      aspiration of the mass for culture, interval follow-up to seek evidence of
      growth, or dismissal.

PMID- 9015047
TI  - Blood flow and liver imaging.

PMID- 9015048
TI  - Recent issues in breast cancer detection and the premarket approval by the Food
      and Drug Administration of a US system for breast lesion evaluation: what
      happened to science?

PMID- 9015049
TI  - Science is alive and well at the Food and Drug Administration.

PMID- 9015050
TI  - Antiphospholipid syndrome: patterns of life-threatening and severe recurrent
      vascular complications.
AB  - PURPOSE: To demonstrate the variety and recurrence patterns of severe arterial
      and venous thromboembolic events that occur in patients with the antiphospholipid
      syndrome. MATERIALS AND METHODS: Radiology records were reviewed in 800 of 1,633
      patients with positive test results of antiphospholipid syndrome. Patients with
      radiologic evidence of antiphospholipid syndrome and no other hypercoagulable
      state were included if the observed thromboembolic event met one or more of four
      criteria for severity: extreme complications or mortality, three or more
      recurrent events, unusually young age, and/or unusual sites affected. RESULTS: In
      the 24 patients who met the selection criteria, 72 thromboembolic episodes and 56
      (78%) recurrences were found. Arterial complications included aortic occlusions,
      visceral infarctions, upper- and lower-extremity arterial thrombosis, strokes,
      and repeated graft occlusions. Venous complications included portal vein
      thrombosis, transverse and sagittal sinus thrombosis, upper- and lower-extremity
      thrombosis, and recurrent pulmonary emboli. CONCLUSION: Vascular complications of
      antiphospholipid syndrome include serious and life-threatening events. Primary
      thromboembolic episodes often recur at the same site or within the same system
      (arterial vs venous system). These events can also trigger a rapid succession of
      critical thrombotic episodes at multiple sites.

PMID- 9015051
TI  - MR imaging of soft-tissue changes after percutaneous transluminal angioplasty and
      stent placement.
AB  - PURPOSE: To evaluate the different tissue reactions at magnetic resonance (MR)
      imaging after balloon dilation and placement of covered and uncovered stents.
      MATERIALS AND METHODS: Contrast material-enhanced MR imaging was performed in 14
      patients with polyester-covered nitinol stents, 10 patients with conventional
      metallic stents, and 12 patients who underwent peripheral percutaneous
      transluminal angioplasty. Lesions were located in the subclavian, iliac, femoral,
      and popliteal arteries. RESULTS: MR imaging demonstrated perivascular soft-tissue
      inflammation in 11 of 14 (79%) patients with polyester-covered stents. Eight
      (57%) of these patients showed clinical symptoms. No reaction was found among the
      group with uncovered stents and those who underwent peripheral percutaneous
      transluminal angioplasty. CONCLUSION: The polyester-covered nitinol stent can
      induce systemic and severe local reactions. These reactions seem to be specific
      to this type of stent. No definite cause has been established, although the
      phenomenon appears to be self-limiting.

PMID- 9015052
TI  - Hemodynamic significance of renal artery stenosis: digital subtraction
      angiography versus systolically gated three-dimensional phase-contrast MR
      angiography.
AB  - PURPOSE: To compare digital subtraction angiography with three-dimensional phase
      contrast magnetic resonance (MR) angiography in detection of significant renal
      artery stenosis. MATERIALS AND METHODS: Sixteen patients underwent digital
      subtraction angiography and systolically gated three-dimensional phase-contrast
      MR angiography within 1 week. Scoring of stenosis on MR angiograms was based on
      presence and length of a flow void and quality of flow signal intensity in the
      distal part of the artery. Intraarterial pressure measurement was the reference
      standard for hemodynamically significant renal artery stenosis. RESULTS: MR
      angiography depicted two of five patent accessory arteries. Comparison of digital
      subtraction angiography and MR angiography with intraarterial pressure
      measurements was possible in 25 main renal arteries. In 13 arteries, a pressure
      gradient of more than 15 mm Hg was found. Digital subtraction angiography
      depicted 10 of these stenoses (sensitivity, 77%; specificity, 92%). A flow void
      was present at MR angiography in eight stenoses (sensitivity, 62%; specificity,
      83%). In 12 of the stenosed vessels, distal flow signal intensity was impaired at
      MR angiography (sensitivity, 92%; specificity, 75%). There was no difference
      between the two modalities (P > .05) in grading hemodynamic significance of renal
      artery stenosis. CONCLUSION: Systolically gated MR angiography and digital
      subtraction angiography are equally effective in depicting hemodynamically
      significant stenoses in the main renal arteries. MR angiography, however, is not
      adequate in depiction of accessory renal arteries.

PMID- 9015053
TI  - Patterns of anesthesia and nursing care for interventional radiology procedures:
      a national survey of physician practices and preferences.
AB  - PURPOSE: Through a survey of interventional radiologists, to document patterns of
      conscious sedation, nursing assistance, and care before and after the
      intervention and to compare demographics and different interventional radiology
      practices. MATERIALS AND METHODS: The survey was sent to the 1,713 members of the
      Society of Cardiovascular and Interventional Radiology. The levels of sedation
      were categorized according to the following grading scale commonly employed by
      anesthesiologists: awake/alert, drowsy/arousable, asleep/arousable, deep
      sedation, and general anesthesia. The drugs used for sedation were recorded. The
      procedures were categorized as diagnostic vascular or visceral or therapeutic
      vascular or visceral. Data were available for most standard vascular and visceral
      procedures. RESULTS: Six hundred thirty-four (37%) interventional radiologists
      responded, and 500,000 procedures were analyzed. Most (90%) therapeutic
      procedures employed the drowsy/arousable level of sedation. Eighty-seven percent
      of respondents had the assistance of a full-time radiology nurse, 90% reported
      routine use of blood pressure or pulse oximetry monitoring, and 75% reported
      daily rounds were performed by physicians. CONCLUSION: The data supply useful
      background information regarding the use of anesthesia, periprocedural
      monitoring, clinical assessment, and nursing care.

PMID- 9015054
TI  - Palliation of inoperable esophageal carcinoma: a prospective randomized trial of
      laser therapy and stent placement.
AB  - PURPOSE: A prospective, randomized comparison of the result of endoscopic laser
      therapy and that of placement of self-expandable metallic endoprostheses was
      performed to determine which method provides the best palliation of dysphagia in
      patients with inoperable esophageal carcinoma. MATERIALS AND METHODS: Sixty
      patients participated in the study. Twenty-three were randomly assigned to
      undergo plastic-covered stent placement, 19 to undergo uncovered stent placement,
      and 18 to undergo laser therapy. The quality of swallowing was assessed with the
      dysphagia score, which ranged from 0 for normal swallowing to 4 for complete
      dysphagia. RESULTS: The mean improvement in dysphagia score was 2 and ranged from
      -1 to 3 in patients who underwent placement of plastic-covered stents, was 2 and
      ranged from 0 to 4 in those who underwent placement of uncovered stents, and was
      1 and ranged from 0 to 2 in those who underwent laser therapy. Six of 23 (26%)
      plastic-covered stents migrated, whereas none of the uncovered stents did so (P <
      .02). Tumor ingrowth through uncovered stents occurred in five of 19 patients
      (26%). CONCLUSION: Placement of metallic esophageal endoprostheses is
      substantially better than endoscopic laser therapy for palliation of dysphagia in
      patients with inoperable esophageal carcinoma. Use of uncovered and plastic
      covered metallic stents provides equal palliation in patients with dysphagia.

PMID- 9015055
TI  - Malignant esophageal obstruction and esophagorespiratory fistula: palliation with
      a polyethylene-covered Z-stent.
AB  - PURPOSE: To prospectively evaluate the clinical efficacy of polyethylene-covered
      metallic Z-stents in treatment of dysphagia secondary to malignant esophageal
      obstruction and esophagorespiratory fistula. MATERIALS AND METHODS: Thirty-five
      patients with dysphagia due to malignant esophageal obstruction (n = 32) and
      esophagorespiratory fistula (n = 3) were treated with polyethylene-covered
      Gianturco-Rosch Z-stents. RESULTS: Thirty-nine stents were placed in 35 patients.
      Stent placement was technically successful in all patients. Improvement in
      dysphagia was achieved in 34 of 35 patients. The average dysphagia score
      decreased from 3.1 (dysphagia to liquids) to 0.6 (essentially normal diet). An
      esophagorespiratory fistula was completely sealed in two of three patients. All
      35 patients were followed up clinically at 1 day and 1 week and at 3-month
      intervals (range, 1 week to 18 1/2 months; mean, 4.8 months). Recurrent dysphagia
      or aspiration occurred in only three of 34 (9%) patients whose disease was
      initially palliated and was easily treated in all cases. Nine complications
      occurred in eight patients (23%) and included chest pain that required analgesia
      (n = 3), food impaction (n = 1), stent migration (n = 2), and upper
      gastrointestinal tract hemorrhage (n = 3). CONCLUSION: Polyethylene-covered
      stents are a relatively safe and effective means of long-term palliation in
      patients with severe malignant esophageal obstruction and esophagorespiratory
      fistula. These stents are easily deployed, and the rate of stent migration is
      relatively low.

PMID- 9015056
TI  - Double-contrast barium examination of the upper gastrointestinal tract with
      nonendoscopic biopsy: findings in 100 patients.
AB  - PURPOSE: To evaluate the performance of double-contrast barium examination of the
      upper gastrointestinal tract augmented with nonendoscopic gastric mucosal biopsy.
      MATERIALS AND METHODS: One hundred twenty-six patients (aged 9-81 years)
      underwent double-contrast barium examination of the upper gastrointestinal tract
      and nasogastric biopsy. Pathology reports were recovered for 100 patients. These
      patients' records were searched for procedural complications, sufficiency of
      biopsy tissue, diagnoses among various age groups, and radiographic findings.
      RESULTS: Forty-nine (49%) of the 100 patients had biopsy-proved Helicobacter
      pylori infection with chronic active gastritis. Twenty-one patients (21%) with H
      pylori-negative biopsy specimens had chronic gastritis. One patient with
      eosinophilic gastritis and one with granulomatous gastritis were identified.
      Twenty-nine patients (29%) had negative biopsy results. Nineteen (30%) of the
      patients with negative barium studies had a positive biopsy specimen, and four
      (6%) of the patients with positive barium studies had negative biopsy specimens.
      Eight patients (8%) had a second diagnosis of intestinal metaplasia. CONCLUSION:
      Use of double-contrast barium examination of the upper gastrointestinal tract
      combined with nonendoscopic biopsy is quick and safe and can provide reliable
      histologic information to the primary care physician.

PMID- 9015057
TI  - Barium sulfate: a new (old) contrast agent for diagnosis of postoperative
      esophageal leaks.
AB  - PURPOSE: To determine whether esophagography with use of barium alone is safe for
      detection of postoperative leaks of the esophagus. MATERIALS AND METHODS: A
      review was performed of 29 postoperative esophagograms that showed 29 leaks in 12
      patients. All studies were performed with a 50% dilution of barium sulfate. Leak
      volumes were calculated as the product (in cubic centimeters) of the length,
      width, and height. The safety and efficacy of barium were determined on the basis
      of development of mediastinitis and retention of barium in the mediastinum that
      would interfere with subsequent patient care. RESULTS: In 11 of the 12 patients,
      follow-up studies were performed 4-48 days (mean, 10.2 days) after diagnosis.
      Leaks were 0.25-375 cm3 (mean, 31.4 cm3). In five of 17 (29%) follow-up
      procedures, small amounts of residual barium were detectable on the scout
      radiograph, none of which interfered with interpretation of the new images.
      During a follow-up period of 7-448 days (mean, 226 days), no cases of
      mediastinitis were found. CONCLUSION: Esophagography can be performed safely with
      barium to rule out an anastomotic esophageal leak.

PMID- 9015058
TI  - Appendicitis: use of arrowhead sign for diagnosis at CT.
AB  - PURPOSE: To determine the frequency of collection of a contrast medium in the
      upper portion of the cecum, which the authors call the arrowhead sign, on
      computed tomographic (CT) scans of the lower abdomen and to assess the
      sensitivity and specificity of this sign for appendicitis. MATERIALS AND METHODS:
      One hundred consecutive patients clinically suspected of having appendicitis
      prospectively underwent helical CT limited to the lower abdomen. Contrast media
      were administered orally and by means of an enema. Each scan was reviewed for the
      arrowhead sign, and the findings were correlated with surgical and pathologic
      results or clinical follow-up findings. RESULTS: The arrowhead sign was present
      in 17 of 56 cases (30%) of appendicitis and in no case of excluded appendicitis.
      It allowed the unequivocal diagnosis of appendicitis in four cases (7%) of
      otherwise non-specific right lower-quadrant inflammation and in one case (2%) of
      subtle appendicitis seen at CT. CONCLUSION: The arrowhead sign is an often
      present, highly specific sign of appendicitis that can add specificity to the
      diagnosis of right lower-quadrant inflammatory processes at CT.

PMID- 9015059
TI  - Systemic mastocytosis: CT and US features of abdominal manifestations.
AB  - PURPOSE: To study the imaging findings in patients with systemic mastocytosis and
      to correlate the findings with the severity of disease on the basis of an
      established classification system. Pathologic findings, when available, were
      correlated with imaging findings. MATERIALS AND METHODS: Computed tomographic
      (CT) and ultrasound (US) scans and corresponding pathologic findings, when
      available, were retrospectively reviewed in 27 patients with systemic
      mastocytosis. RESULTS: Only five (19%) of the patients in our series had normal
      abdominal CT and/or US examination results. Common abdominal imaging findings
      associated with systemic mastocytosis were hepatosplenomegaly, retroperitoneal
      adenopathy, periportal adenopathy, mesenteric adenopathy, thickening of the
      omentum and the mesentery, and ascites. Less common findings included hepatofugal
      portal venous flow, Budd-Chiari syndrome, cavernous transformation of the portal
      vein, ovarian mass, and complications such as chloroma. The findings were more
      common in patients with category II and those with category III disease.
      CONCLUSION: Abdominal findings at CT and US are common in patients with systemic
      mastocytosis. Although the findings in patients with systemic mastocytosis are
      not specific to the disease, they are useful in directing further studies for
      diagnostic confirmation and in estimating the extent of systemic involvement.

PMID- 9015060
TI  - Peritoneocele: visualization with defecography and peritoneography performed
      simultaneously.
AB  - PURPOSE: To evaluate the use of simultaneous defecography and peritoneography
      (defecoperitoneography) in patients with an unexplained widening of the
      rectovaginal space noted at defecography. MATERIALS AND METHODS: Twenty-two
      patients with unexplained widening of the rectovaginal space noted at
      defecography were studied with defecoperitoneography. Defecoperitoneography was a
      combination of defecography and peritoneography with water-soluble contrast
      medium administered intraperitoneally. RESULTS: The outline and movements of the
      peritoneum and alterations in the pelvic peritoneal cavity could be visualized
      with defecoperitoneography during the dynamic act of defecation. Unexplained
      widening of the rectovaginal space was completely due to a peritoneocele in 14
      patients and partially due to a peritoneocele in six patients. In two patients,
      there was no peritoneocele. Only nine of 22 patients had bowel in the unexplained
      widening (enterocele). Three patients had a rectal peritoneocele; six, a septal
      peritoneocele; one, a vaginal peritoneocele; and 10, a combination of these
      findings. CONCLUSION: Visualization of the pelvic floor with
      defecoperitoneography is improved compared with visualization with defecography
      alone.

PMID- 9015061
TI  - Fulminant hepatic failure: observation with serial CT.
AB  - PURPOSE: To determine the imaging characteristics of fulminant hepatic failure at
      serial computed tomography (CT) and to assess if any CT findings have prognostic
      value. MATERIALS AND METHODS: In 40 patients, 207 CT scans were analyzed
      retrospectively. Thirty-four patients had fulminant hepatic failure (acute in
      seven and subacute in 27), and six had late-onset hepatic failure. Twenty-one
      patients died of hepatic failure. CT was performed soon after the onset of coma
      and repeated weekly. Liver volume was measured by tracing the hepatic contour and
      summing the areas to estimate whole-liver volume. RESULTS: Liver volumes in
      survivors (n = 19) and nonsurvivors (n = 21), respectively, were 1,090 cm3 +/-
      300 and 830 cm3 +/- 240 at initial CT and 1,130 cm3 +/- 310 and 700 cm3 +/- 280
      at last CT (P = .0001). III-defined hypoattenuating areas were noted in 20
      patients and were distributed in a solitary (n = 13), multiple (n = 6), or
      diffuse (n = 1) pattern. At follow-up CT, the area of hypoattenuation increased
      in six patients (five nonsurvivors) and disappeared or markedly decreased in four
      survivors. An increase in or late occurrence of ascites was noted in 15 patients
      (14 nonsurvivors, P = .0001). CONCLUSION: Liver volumes at the initial and last
      CT examinations and an increase in or late occurrence of ascites are useful
      prognostic findings.

PMID- 9015062
TI  - Nodular hepatocellular carcinomas: detection with arterial-, portal-, and delayed
      phase images at spiral CT.
AB  - PURPOSE: To evaluate the effectiveness of three-phase spiral computed tomography
      (CT) for the evaluation of nodular hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: Images obtained at three-phase spiral CT in 45 patients with 81 nodular
      HCCs were reviewed. Images were obtained with 10-mm collimation and 10 mm/sec
      table speed during intravenous administration of 2 mL/kg 68% nonionic contrast
      material at a rate of 3 mL/sec. Hepatic arterial-phase (AP), portal-phase (PP),
      and delayed-phase (DP) images were obtained 25-30 seconds, 60-70 seconds, and 300
      seconds, respectively, after injection of the contrast material. Lesion
      detectability and conspicuity were compared among these three protocols by two
      readers. RESULTS: The AP images depicted a statistically significantly larger
      number of lesions (n = 67), although the differences in the number of lesions
      depicted between the PP and DP images were not statistically significant. Twenty
      one lesions were detected only with the AP images, three with the PP images, and
      seven with the DP images. The most clearly visualized lesions were most commonly
      depicted on the AP images (n = 47) rather than the PP images (n = 11) or the DP
      images (n = 23). CONCLUSION: Lesion detection and conspicuity were best with the
      AP images. However, some lesions were detected only with the DP and PP images, so
      that maximum lesion visualization is achieved by using all three phases.

PMID- 9015063
TI  - Focal liver lesions: characterization with conventional spin-echo versus fast
      spin-echo T2-weighted MR imaging.
AB  - PURPOSE: To compare prospectively the diagnostic accuracy of T2-weighted
      conventional spin-echo (SE) and fast SE magnetic resonance (MR) imaging for
      differentiation of benign (hemangiomas or cysts) from malignant (metastases or
      hepatocellular carcinoma) liver lesions. MATERIALS AND METHODS: Fifty-three
      patients with 55 confirmed liver lesions (20 hemangiomas, eight cysts, 22
      metastases, four hepatocellular carcinomas, one malignant fibrous histiocytoma)
      underwent T2-weighted conventional SE (repetition time msec/echo time [TE] msec =
      3,100/ 80,160) and fast SE (5,000-5,000/99-104 [effective TE]) MR imaging at 1.5
      T. The images were evaluated quantitatively (lesion-liver signal intensity ratio
      and lesion T2 index [SIlesion TE80/SIlesion TE160, where SI = signal intensity]
      and qualitatively (blinded reading) by using receiver operating characteristic
      analysis. RESULTS: Quantitatively, the T2 index (Az = .988) was more accurate
      than the signal intensity ratio at conventional SE (Az = .920) and fast SE (Az =
      .910) imaging (P < .05). Qualitatively, there was no statistically significant
      difference between the blinded reading of conventional SE (Az = .988) and fast SE
      (Az = .986) images in lesion characterization (benign vs malignant). There was a
      trend, however, toward superiority of conventional SE imaging for evaluation of
      "hypervascular" metastases (n = 9). CONCLUSION: With the specific parameters
      used, conventional SE and fast SE images provide equal accuracy for
      characterization of focal liver lesions. In patients with hypervascular
      metastases, double-echo conventional SE images may be preferable.

PMID- 9015064
TI  - Hepatic enhancement and metastatic lesion conspicuity on CT scans: influence of
      intravenous glucagon and oral CT contrast material.
AB  - PURPOSE: To determine the effect of glucagon and orally administered contrast
      material on hepatic enhancement and metastatic lesion conspicuity on computed
      tomographic (CT) scans. MATERIALS AND METHODS: Nine patients with a history of
      hepatic metastasis underwent two CT examinations with intravenously administered
      contrast material. Each patient was given orally administered CT contrast
      material for the first examination. No oral contrast material was given in the
      second examination. Five patients underwent the initial CT with intravenous
      administration of 1 mg of glucagon; the second examination was performed without
      glucagon. Four patients were administered glucagon before the second examination,
      but no glucagon was administered before the first. Attenuation in the liver,
      portal vein, and aorta was measured by observers blinded to whether the patient
      had been given glucagon. Lesion conspicuity was rated on a continuous scale.
      RESULTS: Greater mean hepatic enhancement was noted on scans of patients in whom
      oral contrast material was administered (mean, 52 HU) versus those in whom no
      oral contrast material was administered (mean, 47 HU; P = .019). Glucagon was not
      associated with greater hepatic enhancement. Neither oral contrast material nor
      glucagon had a significant effect on lesion conspicuity. CONCLUSION: Oral CT
      contrast material is associated with a small increase in hepatic enhancement that
      does not appear to be clinically important. Glucagon does not appear to affect
      hepatic enhancement or lesion conspicuity in humans.

PMID- 9015065
TI  - Detection of focal liver lesions: CT of the hepatobiliary system with gadoxetic
      acid disodium, or Gd-EOB-DTPA.
AB  - PURPOSE: To evaluate the efficacy and safety of gadoxetic acid disodium, or Gd
      EOB-DTPA, as a tissue-specific hepatobiliary contrast agent at computed
      tomography (CT) in patients with liver metastases. MATERIALS AND METHODS: Fifteen
      patients with known liver metastases underwent CT before and at 30, 80, and, in
      seven cases, 150 minutes after initiation of intravenous infusion of 0.2, 0.35,
      and 0.5 mmol Gd/kg gadoxetic acid disodium (five patients per dose group).
      Attenuation in liver tissue and metastases was measured at each time point.
      Visualization of metastases, bile ducts, and gallbladder was graded subjectively
      by two investigators aware of the dose administered and the imaging time point.
      Patients were monitored for adverse events clinically, and numerous laboratory
      tests were performed over the 24 hours after administration of the contrast
      material. RESULTS: The net mean increase in liver attenuation with 0.2, 0.35, and
      0.5 mmol Gd/kg was 13 HU +/- 4 (standard deviation), 27 HU +/- 6, and 34 HU +/-
      8, respectively. Visualization of liver metastases with doses of 0.35 and 0.5
      mmol Gd/kg was graded as good or excellent. Visualization of the gallbladder and
      common bile duct with doses of 0.35 and 0.5 mmol Gd/kg was improved from minimal
      to excellent in 89% and 57% of patients, respectively, on 80-minute postcontrast
      scans. No serious adverse events occurred. Four of 15 patients experienced mild
      or moderate adverse events possibly or probably related to the contrast medium.
      Levels of aspartate and alanine aminotransferase increased in three patients by
      12-26 and 21-48 U/L, respectively, from normal or moderately elevated baseline
      levels. These changes may be related to the contrast medium or to the metastases.
      CONCLUSION: Patient tolerance of gadoxetic acid disodium was acceptable, and
      liver enhancement and visualization of liver lesions and the biliary system was
      improved at CT.

PMID- 9015066
TI  - A prototype liver-specific contrast medium for CT: preclinical evaluation of
      gadoxetic acid disodium, or Gd-EOB-DTPA.
AB  - PURPOSE: The suitability of the hepatobiliary contrast medium gadoxetic acid
      disodium, or Gd-EOB-DTPA, for liver enhancement at computed tomography (CT) was
      studied. MATERIALS AND METHODS: CT attenuation levels at 120 kV were measured in
      samples of increasing concentrations of gadolinium (gadoxetic acid disodium) or
      iodine (iopromide) in aqueous solutions in vitro. In dogs, CT attenuation in the
      liver was measured up to 90 minutes after a single intravenous injection of 0.3,
      0.5, and 0.7 mmol Gd/kg gadoxetic acid disodium (three dogs per dose group). In
      addition, three VX2 tumor-bearing rabbits were examined (0.7 mmol Gd/kg).
      RESULTS: In vitro, the CT attenuation of gadolinium is 40% higher than that of
      iodine if calculated per milligram of gadolinium and iodine, respectively. In
      dogs, the median net increase in liver enhancement was 25, 33, and 43 HU with a
      dose of 0.3, 0.5, and 0.7 mmol Gd/kg, respectively. The gallbladder and bile
      ducts became clearly visible. In rabbits, liver enhancement of 25 HU provided
      improved visualization of the unenhanced tumor. CONCLUSION: Because of the higher
      CT attenuation of gadolinium compared with iodine and because of its liver
      specific uptake, gadoxetic acid disodium is a contrast medium that may improve
      diagnosis of pathologic liver conditions at CT.

PMID- 9015067
TI  - MR imaging of ductal carcinoma in situ.
AB  - PURPOSE: To investigate the ability of magnetic resonance (MR) imaging to depict
      ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Between January 1992 and
      April 1996, 330 women underwent MR imaging before excisional biopsy. Of these,
      101 women had carcinoma, 19 of whom had DCIS. The MR imaging findings in the 19
      women were reviewed. RESULTS: Thirteen of 19 patients had pure DCIS. The mean
      lesion diameter was 10 mm (range, 2-22 mm). MR imaging enabled identification of
      DCIS in 10 (77%) of the 13 cases as ductal enhancement (n = 6), regional
      enhancement (n = 3), or a peripherally enhancing mass (n = 1). The three lesions
      not identified had a mean diameter of 3.7 mm. Six of 19 patients had both DCIS
      and an invasive cancer. In four of these patients, DCIS was identified only at MR
      imaging (mean diameter, 3 mm). In two of six patients, DCIS was not identified at
      MR imaging. CONCLUSION: MR imaging can depict mammographically visible and occult
      foci of DCIS. Some small foci of DCIS detected at mammography and histologic
      examination, however, may be occult at MR imaging.

PMID- 9015068
TI  - Differentiation of benign and malignant breast lesions: MR imaging versus Tc-99m
      sestamibi scintimammography.
AB  - PURPOSE: To compare the accuracies of magnetic resonance (MR) imaging and
      scintimammography in differentiating benign from malignant breast lesions.
      MATERIALS AND METHODS: MR imaging was performed in 66 women with 75 lesions
      during intravenous administration of gadopentetate dimeglumine. Planar and single
      photon emission computed tomographic (SPECT) scintimammography were performed
      (with 740 MBq technetium-99m sestamibi administered intravenously) in all 66
      patients with 75 lesions and in 64 patients with 73 lesions, respectively. MR
      imaging and scintimammographic studies were independently evaluated by using
      signal intensity measurements versus time or focal tracer uptake to differentiate
      benign from malignant lesions. Histopathologic proof was obtained in 63 lesions.
      Twelve lesions were monitored with follow-up. RESULTS: MR imaging was false
      negative in one and false-positive in nine lesions. Planar scintimammography was
      false-negative in 10 and false-positive in six lesions. SPECT scintimammography
      was false-negative in four and false-positive in 10 lesions. Sensitivities and
      specificities for malignancy were, respectively, 96% and 82% for MR imaging, 62%
      and 88% for planar scintimammography, and 83% and 80% for SPECT
      scintimammography. CONCLUSION: Both MR imaging and scintimammography are useful
      in the evaluation of breast cancer. MR imaging is more sensitive and as specific
      as scintimammography.

PMID- 9015069
TI  - Stereotactic core breast biopsy of a minimal carcinoma complicated by a large
      hematoma: a management dilemma.
AB  - Stereotactic core biopsy of a 4-5-mm, suspicious mammographic lesion was
      complicated by substantial hematoma formation in a patient with subsequently
      diagnosed factor XI deficiency. As a result, the small infiltrating ductal
      carcinoma could no longer be identified at mammography to allow accurate needle
      localization for lumpectomy. Sufficient resorption of the hematoma at 3 months
      permitted successful needle localization and lumpectomy. In these cases,
      expectant management may obviate extensive surgery.

PMID- 9015070
TI  - Pulmonary abnormalities and PET data analysis: a retrospective study.
AB  - PURPOSE: To assess methods of standard uptake ratio (SUR) calculation with 2
      deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron emission tomography (PET) in
      indeterminate focal pulmonary abnormalities. MATERIALS AND METHODS: One hundred
      ninety-seven adult patients with indeterminate pulmonary abnormalities had
      complete FDG PET data, consistent methods of data acquisition, and definitive
      diagnosis with tissue biopsy or negative 2-year follow-up findings. PET studies
      were evaluated by using SURs calculated with the average or maximum region-of
      interest pixel value in the numerator and with weight, lean body mass, or body
      surface area in the denominator. RESULTS: One hundred twenty malignant lesions
      and 77 benign processes were identified. Receiver operating characteristic (ROC)
      curve areas were statistically significantly larger with the average rather than
      the maximum pixel value in the calculation of the SUR for any of the three
      denominators (P < or = .05). SURs calculated with weight versus lean body mass
      versus body surface area in the denominator showed no statistically significant
      difference in ROC curve areas. CONCLUSION: SURs determined by using average pixel
      values provide statistically significant improvement in ROC curve areas over
      those determined by using maximum pixel values. Weight, lean body mass, and body
      surface area in the denominator of the SUR calculation provide equivalent ROC
      curve areas and are therefore equivalent in accuracy in this population.

PMID- 9015071
TI  - Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative
      lymph node mapping and sampling.
AB  - PURPOSE: To prospectively compare the accuracy of positron emission tomography
      (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) with that of computed
      tomography (CT) in the nodal staging of non-small cell lung cancer. MATERIALS AND
      METHODS: PET and contrast material-enhanced CT were performed in 47 patients
      suspected of having or with newly diagnosed non-small cell lung cancer. Each
      imaging study was evaluated separately, and nodal stations were localized
      according to the American Thoracic Society mapping system. Extensive lymph node
      sampling (599 nodes from 191 nodal stations) of the ipsi- and contralateral
      tracheobronchial and mediastinal nodal stations was performed at thoracotomy
      and/or mediastinoscopy. Imaging findings were correlated with histopathologic
      staging results. RESULTS: The sensitivity of PET and CT was 89% and 57%,
      respectively, for the staging of N2 or N3 disease in mediastinal nodes;
      specificity was 99% and 94%, respectively; positive predictive value was 96% and
      76%, respectively; negative predictive value was 97% and 87%, respectively; and
      accuracy was 96% and 85%, respectively. In assigning the correct N stage, PET was
      correct in 96% and CT in 79% of cases. CONCLUSION: PET with FDG appears to be
      superior to CT for nodal staging of non-small cell lung cancer.

PMID- 9015072
TI  - Digital chest radiography: effect of temporal subtraction images on detection
      accuracy.
AB  - PURPOSE: To improve early detection of disease in chest radiographs, the authors
      developed a digital processing technique that geometrically warps and subtracts a
      previous radiograph from a current radiograph to produce a temporal subtraction
      image. An observer test was performed to evaluate the effects of the temporal
      subtraction image technique on detection of interval change. MATERIALS AND
      METHODS: Fifty pairs of chest radiographs, including a baseline examination and a
      subsequent radiograph, were selected (25 cases in which potentially important new
      abnormalities had developed, and 25 in which there was no interval change). The
      baseline examination was chosen from multiple prior radiographs to minimize
      initial misregistration. By means of receiver operating characteristic (ROC)
      analysis, the ability of 11 observers to detect pathologic change when viewing
      the paired digitized baseline and subsequent radiographs was compared with their
      ability when viewing the same paired radiographs together with temporal
      subtraction images. Positive cases demonstrated focal new abnormalities that were
      greater than 1 cm in diameter. RESULTS: The mean area (Az) under the ROC curves
      increased from 0.89 without to 0.98 with the temporal subtraction images. When
      the paired digitized previous and current chest radiographs were viewed in
      conjunction with the temporal subtraction images, a significant improvement in
      detection of new abnormalities was achieved (P = .00004), whereas the mean
      interpretation time was reduced by 19.3% (from 52 to 42 seconds, including the
      time to record the score and to move to the next case) (P = .0019). CONCLUSION:
      The temporal subtraction technique can significantly improve sensitivity and
      specificity for detection of interval change in chest radiographs.

PMID- 9015073
TI  - Simulated dose reduction in conventional chest CT: validation study.
AB  - PURPOSE: To validate a technique of computer-simulated dose reduction for
      conventional chest computed tomography (CT). MATERIALS AND METHODS: In 27
      patients, CT scans were obtained at 200, 100, and 40 mAs at two levels. The raw
      data from the 200-mAs scan were modified on a computer workstation to simulate
      the increased noise present on 100- and 40-mAs scans. Real and simulated 100- and
      40-mAs images were independently assessed in random order for overall image
      quality and radiologic findings by four subspecialty-trained chest radiologists
      who were blinded to the technique. The four observers were given paired real and
      simulated images. They were asked to identify the real image and note any
      difference in diagnostic quality. RESULTS: No difference was seen in overall
      image quality or radiologic findings between real and simulated images (P > .05).
      In the paired comparison, 433 of 864 (50.1%) real images were correctly
      identified. CONCLUSION: Computer modification of 200-mAs raw scan data to
      simulate 100- and 40-mAs noise levels produces reconstructed images
      indistinguishable from real 100- and 40-mAs scans. This technique provides
      realistic reduced-dose images without patient radiation exposure and with
      identical image registration and motion artifact.

PMID- 9015074
TI  - Vascular air embolism: location, frequency, and cause on electron-beam CT studies
      of the chest.
AB  - PURPOSE: To determine the frequency and location of venous air emboli that occur
      with the use of electron-beam computed tomographic (CT) studies of the chest.
      MATERIALS AND METHODS: Findings from 677 patients who underwent chest electron
      beam CT with intravenous administration of contrast material were reviewed.
      Unenhanced CT studies were performed in 127 (18.8%) of these patients while the
      intravenous cannula was in place but before injection of contrast material.
      RESULTS: Air emboli were observed on CT studies in 79 (11.7%) of 677 patients.
      Emboli were small (up to three air bubbles less than 1 cm in diameter) in 70
      (10.3%) patients and were moderate (more than three air bubbles or bubbles 1-2 cm
      in diameter) in nine (1.3%) patients. Air emboli were located in the main
      pulmonary artery (n = 54 [8.0%]), superior vena cava (n = 12 [1.8%]), right
      ventricle (n = 10 [1.5%]), subclavian or brachiocephalic vein (n = 6 [0.9%]), and
      right atrium (n = 5 [0.7%]). Seven patients (1.0%) had emboli in more than one
      location. Air emboli were depicted on unenhanced CT scans of seven (5.5%) of 127
      patients. No association was found between the frequency of air embolism and
      injection flow, injection site, or amount or type of contrast agent. CONCLUSION:
      Intravenous administration of contrast material may cause small to moderate-sized
      air emboli. Knowledge of the common locations of emboli can help radiologists
      distinguish them from image artifacts or paravasal air collections.

PMID- 9015075
TI  - Detection of recurrent nasopharyngeal carcinoma: MR imaging versus CT.
AB  - PURPOSE: To compare the use of magnetic resonance (MR) imaging and computed
      tomography (CT) in detection of recurrent nasopharyngeal carcinoma. MATERIALS AND
      METHODS: Forty-five sets of CT and MR images were obtained in 34 patients. The
      images were placed in three categories: (a) clinically or radiologically abnormal
      findings in patients who underwent biopsy (n = 16), (b) clinically normal and
      radiologically borderline findings in patients who were followed up clinically
      and radiologically (n = 10), and (c) clinically and radiologically normal
      findings in patients who were monitored only clinically (n = 19). All images were
      read by two observers independently. RESULTS: There were nine positive and seven
      negative biopsy results. All patients in the latter two categories had normal
      findings at followup. CT had a sensitivity of 45% and 67% and a specificity of
      64% and 70% for each of the two observers. MR imaging had a sensitivity of 56%
      (for both observers) and a specificity of 78% and 83%. The kappa test for
      interobserver concordance was 0.53 for CT and 0.66 for MR imaging. CONCLUSION:
      Both modalities have relatively low sensitivity and moderate specificity in
      detection of tumor recurrence and in distinguishing recurrence from post
      radiation therapy changes.

PMID- 9015076
TI  - Necrotizing fasciitis of the head and neck: role of CT in diagnosis and
      management.
AB  - PURPOSE: To determine the characteristic diagnostic features of necrotizing
      fasciitis and to evaluate the role of computed tomography (CT) in its management.
      MATERIALS AND METHODS: Fourteen patients with surgically proved necrotizing
      fasciitis of the extracranial head and neck were examined with contrast material
      enhanced CT. Clinical, radiologic, surgical, pathologic, and anatomic findings at
      admission and after initial treatment were analyzed retrospectively. RESULTS:
      Constant CT features of necrotizing fasciitis were diffuse thickening and
      infiltration of the cutis and subcutis (cellulitis); diffuse enhancement and/or
      thickening of the superficial and deep cervical fasciae (fasciitis); enhancement
      and thickening of the platysma, sternocleidomastoid muscle, or strap muscles
      (myositis); and fluid collections in multiple neck compartments. Inconstant CT
      features included gas collections, mediastinitis, and pleural or pericardial
      effusions. All patients underwent extensive surgical debridement. Follow-up CT
      scans in 11 patients revealed clinically unsuspected progression of the
      inflammatory process in previously unaffected areas, a finding that warranted
      additional surgery in nine patients. Twelve patients survived, and two patients
      died of septic shock and aspiration pneumonia despite intensive surgical and
      medical treatment. CONCLUSION: Early recognition of necrotizing fasciitis with CT
      enables appropriate surgical treatment. CT may also be a useful guide in further
      patient treatment after initial surgical debridement.

PMID- 9015077
TI  - Sinonasal undifferentiated carcinoma: CT and MR imaging of an uncommon neoplasm
      of the nasal cavity.
AB  - PURPOSE: To determine the computed tomographic (CT) and magnetic resonance (MR)
      imaging appearance of sinonasal undifferentiated carcinoma. MATERIALS AND
      METHODS: Findings from 11 patients with histopathologically proved sinonasal
      undifferentiated carcinoma were retrospectively reviewed. All 11 patients had
      undergone CT, and six of them had undergone MR imaging. RESULTS: The tumors
      usually were large (larger than 4 cm in maximum dimension in eight patients), had
      poorly defined margins, and arose within the ethmoid sinuses and superior nasal
      cavity. The aggressive nature of the tumor was demonstrated by bone destruction
      (n = 10) and by invasion of adjacent structures, including paranasal sinuses (n =
      10), anterior fossa (n = 7), orbits (n = 4), pterygopalatine fossa (n = 2),
      parapharyngeal space (n = 1), and cavernous sinus (n = 1). On contrast material
      enhanced CT scans, all tumors were enhanced to varying degrees. They tended to be
      noncalcified (n = 10) and often caused sinus obstruction (n = 10). MR signal
      intensity of the lesions was isointense to muscle on T1-weighted images in all
      six patients and iso- to hyperintense on T2-weighted images in five patients.
      Heterogeneous enhancement of tumors was seen on gadolinium-enhanced images.
      CONCLUSION: Sinonasal undifferentiated carcinoma cannot be distinguished from
      other tumors of this region (with the possible exception of melanoma) on the
      basis of imaging features.

PMID- 9015078
TI  - Saccular intracranial aneurysms: endovascular treatment with mechanical
      detachable spiral coils.
AB  - PURPOSE: To evaluate endovascular treatment of saccular intracranial aneurysms
      with mechanical detachable spiral coils. MATERIALS AND METHODS: Fifty-three
      patients with 56 saccular aneurysms underwent endovascular treatment with spiral
      coils. All but five had symptomatic subarachnoid hemorrhage staged according to
      the Hunt and Hess classification as follows: stage IV or V (n = 20), stage III (n
      = 10), stage I or II (n = 20), and stage 0 (asymptomatic [n = 6]). RESULTS: Forty
      seven aneurysms were occluded (100% occlusion) on follow-up angiograms with the
      following time distribution: 24 months for six aneurysms (six patients), 12
      months for 14 aneurysms (11 patients), 6 months for 13 aneurysms (13 patients), 4
      months for four aneurysms (four patients), and only immediate postprocedure study
      for 16 aneurysms (16 patients) (excludes two deaths and one failure). CONCLUSION:
      In this relatively small group, endovascular treatment with mechanical detachable
      spiral coils had a success rate of 90%, and it appears to be a rapid, reliable,
      and relatively safe technique in the treatment of life-threatening subarachnoid
      hemorrhage.

PMID- 9015079
TI  - Proton MR spectroscopy after acute central nervous system injury: outcome
      prediction in neonates, infants, and children.
AB  - PURPOSE: To evaluate the usefulness of proton magnetic resonance (MR)
      spectroscopy in predicting 6-12-month neurologic outcome in children after
      central nervous system injuries. MATERIALS AND METHODS: Localized single-voxel,
      20-msec-echo-time MR spectra (including N-acetylaspartate [NAA], choline [Ch],
      creatine and phosphocreatine [Cr]) were obtained in the occipital gray matter in
      82 patients and 24 control patients. Patient age groups were defined as neonates
      (< or = 1 month [n = 23]), infants (1-18 months [n = 31]), and children (> or =
      18 months [n = 28]). Metabolite ratios and the presence of lactate were
      determined. Linear discriminant analysis-with admission clinical data, proton MR
      spectroscopy findings, and MR imaging score (three-point scale based on severity
      of structural neuroimaging changes)-was performed to help predict outcome in each
      patient. Findings were then compared with the actual 6-12-month outcome assigned
      by a pediatric neurologist. RESULTS: Outcome on the basis of proton MR
      spectroscopy findings combined with clinical data and MR imaging score was
      predicted correctly in 91% of neonates and in 100% of infants and children.
      Outcome on the basis of clinical data and MR imaging score alone was 83% in
      neonates, 84% in infants, and 93% in children. The presence of lactate was
      significantly higher in patients with poor outcome than in patients with good
      moderate outcomes in all three age groups (neonates, 38% vs 5%; infants, 87% vs
      5%; children, 64% vs 10% [chi 2 test, P < .02]). In children with poor outcomes,
      NAA/Cr ratios were significantly lower in infants (P = .006) and children (P <
      .001), and NAA/Ch ratios were significantly lower in infants (P = .001) and
      neonates (P = .05). CONCLUSION: Findings at proton MR spectroscopy helped predict
      long-term neurologic outcomes in children after central nervous system injury.

PMID- 9015080
TI  - Brain tumors: detection with C-11 choline PET.
AB  - PURPOSE: To evaluate the effectiveness of positron emission tomography (PET) with
      carbon-11 choline in brain tumor imaging. MATERIALS AND METHODS: A rat glioma
      cell line (C6) was incubated with C-14 choline; the time course of uptake and
      metabolism was determined in vitro. C-11 choline was injected intravenously in
      tumor-bearing rats; the time course of distribution in organs was determined. C
      11 choline also was injected intravenously in 20 patients (aged 6-86 years) with
      brain tumors and two volunteers (aged 38 and 58 years); distribution of the
      tracer in the brain was determined. Regional cerebral blood flow was measured by
      using oxygen-15 water on the same day. RESULTS: C-14 choline was metabolized to
      phosphoryl choline in glioma cells. The uptake of C-11 choline by glioblastoma
      cells was three to four times higher than that in the rat brain. All brain tumors
      took up more C-11 choline than did normal brain; thus, brain tumors that were not
      treated, as well as those that were treated with surgery or radiation therapy,
      were depicted. The tumor-normal brain uptake ratio of C-11 choline in brain tumor
      did not correlate with the O-15 water regional blood flow in the corresponding
      area. CONCLUSION: C-11 choline PET can depict brain tumors effectively. This
      method was clinically useful in patients who had undergone surgery.

PMID- 9015081
TI  - Three-dimensional hippocampal MR morphometry with high-dimensional transformation
      of a neuroanatomic atlas.
AB  - PURPOSE: To test automated three-dimensional magnetic resonance (MR) imaging
      morphometry of the human hippocampus, to determine the potential gain in
      precision compared with conventional manual morphometry. MATERIAL AND METHODS: A
      canonical three-dimensional MR image atlas was used as a deformable template and
      automatically matched to three-dimensional MR images of 10 individuals (five
      healthy and five schizophrenic subjects). A subvolume containing the hippocampus
      was defined by using 16 landmarks that constrained the automated search for
      hippocampal boundaries. Transformation of the hippocampus template was
      automatically performed by using global pattern matching through a sequence of
      low-then high-dimensional translations, rotations, and scalings. RESULTS: The
      average test-retest volume difference measured with the automatic method was
      3.1%, compared with the manual test-retest difference of 7.1%. Correlation
      between automated and manually determined volumes demonstrated the validity of
      the automated technique (intraclass correlation coefficient = .86). CONCLUSION:
      The automated method estimates hippocampal volumes with less variability (ie,
      lower variance) than that of manual out-lining.

PMID- 9015082
TI  - Gliomas: correlation of magnetic susceptibility artifact with histologic grade.
AB  - PURPOSE: To determine whether magnetic susceptibility artifact on magnetic
      resonance (MR) images can be used to grade gliomas. MATERIALS AND METHODS: Twenty
      nine patients with gliomas were prospectively examined with spin-echo T1-weighted
      MR imaging without and with contrast material enhancement, spin-echo or fast spin
      echo T2- and proton-density-weighted MR imaging, and gradient-echo T2*-weighted
      MR imaging. Images were reviewed by two neuroradiologists, and susceptibility
      artifacts in the tumor region were graded. Heterogeneity, mass effect, contrast
      enhancement, and necrosis were also graded. Tumors were graded according to the
      World Health Organization classification. RESULTS: Increased susceptibility
      artifact was detected by at least one observer on gradient-echo MR images of 19
      tumors. This feature was seen on only 10 of the spin-echo or fast spin-echo T2
      weighted MR images of lesions. Fifteen neoplasms with increased susceptibility
      artifact detected on MR images by at least one observer were high-grade lesions
      (anaplastic astrocytoma or glioblastoma multiforme). Lesion susceptibility
      artifact detected on T2*-weighted MR images was associated with tumor grade (P <
      .05). CONCLUSION: Susceptibility artifacts on T2*-weighted gradient-echo MR
      images appear to be valuable in the preoperative evaluation of gliomas.

PMID- 9015083
TI  - Quantitative CT evaluation of adrenal gland masses: a step forward in the
      differentiation between adenomas and nonadenomas?
AB  - PURPOSE: To assess the attenuation of the adrenal gland with computed tomography
      (CT) before and after multiple phases of contrast enhancement in both control
      subjects and patients with adenomas and nonadenomas. MATERIALS AND METHODS:
      Seventy-two patients with 78 adrenal masses (41 adenomas, 37 nonadenomas)
      underwent helical CT. Forty subjects served as controls. Unenhanced CT was
      performed followed by enhanced CT at 30, 60, 90, and 180 seconds and 30 minutes.
      RESULTS: At unenhanced CT, mean attenuation was 4 HU +/- 16 for adenomas compared
      with 37 HU +/- 12 for the nonadenomas (P < .001) and 24 HU +/- 3 for normal
      glands. Although the mean attenuation of nonademonas was significantly greater
      than that of adenomas on 60- and 90-second scans (P < .001), there was greater
      overlap in attenuation of the adenomas and nonadenomas than on unenhanced images.
      At 180 seconds, nonadenomas had higher attenuation than adenomas (73 HU +/- 17 vs
      41 HU +/- 18; P < .001). At 30 minutes, all adenomas had attenuation less than 37
      HU, whereas all nonadenomas had attenuation greater than 41 HU. CONCLUSION:
      Delayed-enhanced CT scans obtained 30 minutes after administration of contrast
      material can enable differentiation of adenomas and nonadenomas.

PMID- 9015084
TI  - Communications of the pelvic extraperitoneal spaces and their relation to the
      abdominal extraperitoneal spaces: helical CT cadaver study with pelvic
      extraperitoneal injections.
AB  - PURPOSE: To evaluate flow patterns and anatomic appearances in the pelvic
      extraperitoneal spaces and to determine their relation to the abdominal
      extraperitoneal spaces. MATERIALS AND METHODS: Helical computed tomographic (CT)
      guidance was used for injection of up to 1,000 mL of iodinated contrast material
      into one pelvic extraperitoneal space in each of five cadavers. Staged-volume
      injections into two prevesical spaces, one paravesical space, and one perivesical
      space were followed by helical CT. RESULTS: The injected pelvic extraperitoneal
      spaces freely communicated with each other and with the perirenal and anterior
      and posterior pararenal spaces of the abdomen. This abdominal communication was
      via the large infrarenal space posteriorly and the circumferential
      extraperitoneal spaces about the peritoneal cavity bounded deeply and
      superficially by the parietal peritoneum and transversalis fascia, respectively.
      The contrast material reached the diaphragm superiorly and the femoral vascular
      sheath space and inguinal canals inferiorly. After crossing the midline both
      anterior and posterior to the peritoneal cavity, the contrast material reached
      the mesenteric root in four cadavers and the propericardial space of the thorax
      in two cadavers. CONCLUSION: Intercommunication of the various extraperitoneal
      compartments occurs predominantly via the fascial-defined spaces, which contain
      mainly adipose tissue, but potential conduits exist through the communicating
      neurovascular structures where the fascia is anatomically perforated.

PMID- 9015085
TI  - Correction to a previously published case: recurrence of invasive adrenocortical
      tumor after excision of atypical adenoma.
AB  - A 74-year-old woman had hyperaldosteronemia and an adrenal adenoma that showed no
      evidence of lipid on in-phase and opposed-phase gradient-echo magnetic resonance
      (MR) images. MR images obtained 4 years after resection of the mass showed large
      masses of invasive tumor in the resection site, with small foci of lipid, and
      biopsy results confirmed the presence of an adrenocortical tumor.

PMID- 9015086
TI  - Rotator cuff: evaluation with fast spin-echo versus conventional spin-echo MR
      imaging.
AB  - PURPOSE: To determine if fast spin-echo (SE) magnetic resonance (MR) imaging can
      provide similar information to that of conventional SE imaging for evaluation of
      the rotator cuff. MATERIALS AND METHODS: One hundred twenty-six patients
      underwent MR imaging with conventional SE and non-fat-suppressed fast SE
      sequences (65 patients) or conventional SE and fat-suppressed fast SE sequences
      (61 patients). Two radiologists independently graded the rotator cuff with
      separate and side-by-side assessment of the fast SE and conventional SE images.
      RESULTS: For detection of full-thickness tears, agreement between non-fat
      suppressed fast SE and conventional SE images was 93.8% (kappa = 0.78 [good]) and
      95.4% (kappa = 0.82 [very good]) for the two readers, respectively, and agreement
      between fat-suppressed fast SE and conventional SE images was 98.4% (kappa = 0.96
      [very good]) and 91.8% (kappa = 0.73 [good]) for the two readers, respectively.
      Rotator cuff grading was similar for fast SE and conventional SE: weighted kappa
      = 0.77 (good) and 0.68 (good) for non-fat-suppressed and weighted kappa = 0.83
      (very good) and 0.67 (good) for fat-suppressed fast SE images for the two
      readers, respectively. CONCLUSION: Fast SE sequences yield similar
      interpretations as those obtained with a conventional SE sequence for evaluation
      of the rotator cuff.

PMID- 9015087
TI  - Can running cause the appearance of marrow edema on MR images of the foot and
      ankle?
AB  - PURPOSE: To determine if runners have an increased prevalence of marrow edema in
      the foot and ankle compared with nonrunners at magnetic resonance (MR) imaging.
      MATERIALS AND METHODS: Ankles and feet were imaged in 20 runners and 12
      nonrunners with a fast short inversion time inversion-recovery sequence at 1.5 T.
      Edema within each bone was graded from 0 (no edema) to 3 (severe edema). Total
      scores for each subject equaled the sum of the grades. RESULTS: Reader 1 found
      edema in 16 of 20 runners and four of 12 nonrunners (P < .04); runners had a mean
      score of 4.7 and nonrunners had a mean score of 0.9 (P < .006). The average
      number of bones with edema was 3.4 for runners and 0.7 for nonrunners (P < .005).
      Reader 2 found edema in 16 of 20 runners and two of 12 nonrunners (P < .002);
      runners had a mean score of 4.5 and nonrunners had a mean score of 0.3 (P <
      .001). The average number of bones with edema was 3.6 for runners and 0.3 for
      nonrunners (P < .001). CONCLUSION: When the fast short inversion time inversion
      recovery sequence is performed, edema seen within the marrow of runners on MR
      images may be due to exercise alone.

PMID- 9015088
TI  - Methotrexate osteopathy in patients with osteosarcoma.
AB  - PURPOSE: To determine the frequency of osteopathy in patients treated with high
      dose, short-term, intravenous methotrexate for osteosarcoma and whether this
      complication varies with patient age and methotrexate dose. MATERIALS AND
      METHODS: Radiographs and available scintigrams of 87 patients with osteosarcoma
      who received high-dose methotrexate were reviewed retrospectively for severe
      osteopenia, dense zones of provisional calcification, insufficiency fractures,
      and involvement of multiple bones. At least three of these radiographic
      abnormalities were required for the diagnosis of osteopathy. Patients with bone
      metastases were excluded. RESULTS: Eight patients (cumulative dose, 60-144 g/m2)
      exhibited adverse skeletal findings similar to those described in children with
      leukemia who received low-dose maintenance methotrexate. Images showed severe
      osteopenia (n = 8), dense zones of provisional calcification (n = 8), multiple
      bone involvement (n = 6), and insufficiency fractures (n = 6). Most commonly
      affected sites were the distal tibia (n = 7), distal radius and proximal humerus
      (n = 3), and calcaneus and public ramus (n = 2). The affected patients were
      significantly younger (mean age, 9.2 years; P < .001) than the 79 unaffected
      patients (mean age, 14.9 years). CONCLUSION: Osteopathy occurs in approximately
      9% of children who receive high-dose methotrexate for osteosarcoma and is
      substantially more likely to occur in younger patients. The complication rate was
      not directly dose dependent.

PMID- 9015089
TI  - Rapid method for rigorous assessment of radiologic imaging technologies.
AB  - Rapid and rigorous technology evaluation is important for improving quality and
      cost in health care, particularly for swiftly changing, highly technologic fields
      like radiology. Currently, however, evaluations are generally seriously deficient
      in quality, and rigorous evaluations typically require 4 years or more.
      Therefore, the authors developed an appropriate methodology. Its principal
      characteristics include study of outcomes, clinical relevance, multi
      institutional design, intensive communication, experienced data management and
      statistical centers, sophisticated analysis, careful attention to the protocol
      and reference standard, on-site managers, and extensive pretesting and
      refinement. The authors successfully tested the methodology in a seven
      institution study. Completed in 1 1/4 years, the study achieved active
      participation of treating physicians, which much enhanced the clinical relevance
      of the end points studied. The data supported extensive analyses, which included
      the effect of imaging on treatment plans, an important outcome measure. The
      authors report the (limited) difficulties encountered and identify changes to
      ameliorate them. Thus revised, the methodology can serve as a model for future
      technology assessments.

PMID- 9015090
TI  - Testicular blood flow in boys as assessed at color Doppler and power Doppler
      sonography.
AB  - PURPOSE: To investigate at which age testicular blood flow can be demonstrated
      consistently by color Doppler sonography and power Doppler sonography. MATERIALS
      AND METHODS: In this prospective study, 172 normal testes of 86 boys (age range,
      4 days to 15 years) were examined with gray-scale ultrasound, color Doppler
      sonography, and power Doppler sonography. Presence of supratesticular and
      capsular vessels was determined, testicular volumes were assessed, and
      intratesticular vessels were quantified by using a semiquantitative score.
      RESULTS: Supratesticular and capsular vessels were always detectable.
      Demonstration of intratesticular vessels was inconsistent until 8 years of age at
      power Doppler sonography and until 12 years of age at color Doppler sonography.
      Power Doppler sonography depicted more vessels than did color Doppler sonography
      in 37 (22%) testes (P = .001), and it depicted vessels in 13 (25%) of 51 testes
      in which color Doppler sonography could not (P = .0002). Correlation between the
      number of visible intratesticular vessels was slightly closer with age than with
      testicular volume (r = .59, r = .55 for color Doppler sonography and power
      Doppler sonography, respectively). CONCLUSION: Intratesticular blood flow can be
      detected more sensitively and more consistently from a younger age on with power
      Doppler sonography than with color Doppler sonography.

PMID- 9015091
TI  - Accelerated hyperfractionation radiation therapy after lumpectomy and axillary
      lymph node dissection in patients with stage I or II breast cancer: pilot study.
AB  - PURPOSE: To prospectively assess tolerance to accelerated hyperfractionation
      radiation therapy in patients undergoing breast-conservation therapy and to
      exclude, with 90% confidence, a 20% or greater risk of an acute toxic reaction of
      at least grade 3 (severe). MATERIALS AND METHODS: Thirty-seven patients (aged 33
      80 years) with evaluatable cases received 48 Gy in twice-daily 1.6-Gy fractions
      to the breast and regional lymph nodes (if three or more lymph nodes were
      involved) and a boost of 9.6 Gy in twice-daily 1.6-Gy fractions. Acute and late
      effects were scored by using the Radiation Therapy Oncology Group and European
      Organization for the Research and Treatment of Cancer radiation morbidity
      criteria. RESULTS: One patient developed a grade 3 acute skin toxic reaction and
      another grade 3 (continuous) acute edema. There have been no grade 4 (life
      threatening) acute toxic reactions, local recurrences, or cancer- or treatment
      related deaths. CONCLUSION: This breast-conservation accelerated
      hyperfractionation radiation therapy schedule is tolerable. Additional follow-up
      is necessary to determine long-term morbidity and cosmesis, and further study in
      a larger patient group is necessary to confirm efficacy.

PMID- 9015092
TI  - Acute respiratory distress syndrome: CT findings during partial liquid
      ventilation.
AB  - To describe the computed tomographic (CT) appearance of perflubron-filled lungs
      during partial liquid ventilation to treat acute respiratory distress syndrome,
      scans of the thorax were obtained in nine patients between June 1994 and December
      1995. The distribution of perflubron was gravity dependent in four patients, with
      a mean interval of 6.25 days between scanning and perflubron administration; was
      patchy in four patients (mean interval, 16 days); and was homogeneous in one
      patient (interval, 3 days). Extraparenchymal perflubron was seen in intrathoracic
      lymph nodes (n = 4), supraclavicular nodes (n = 2), axillary nodes (n = 1), and
      both the retroperitoneum and the mediastinum (n = 2). In one patient, perflubron
      was seen in a pneumatocele and the pleural space. The distribution of perflubron
      in the lungs is typically gravity dependent.

PMID- 9015093
TI  - Percutaneously implantable catheter-port system: preliminary technical results.
AB  - The function and safety of a percutaneously implantable catheter-port system were
      studied in 44 patients with different diseases (32 patients with malignant
      disease, 11 with peripheral arterial disease, and one with recurrent asthmatic
      attacks). Most patients required repeated local-regional arterial infusion.
      Infection (two patients) and catheter-related complications (10 patients) were
      observed during the follow-up period (maximum length of follow-up, 542 days;
      mean, 177 days). Port migration or leakage did not occur. The data suggest that
      this new catheter-port system is safe and easy to handle.

PMID- 9015094
TI  - MR imaging-guided intravascular procedures: initial demonstration in a pig model.
AB  - With use of an open 1.5-T magnetic resonance (MR) imager and a tracking catheter,
      the authors successfully placed the catheter into the left or right sacral artery
      in pigs. The tracking catheter comprised a 5.3-F percutaneous transluminal
      angioplasty catheter with a small copper radio-frequency coil in its tip. With
      use of the coil as an antenna, the catheter tip position was projected in real
      time onto MR angiography road maps in two planes. Guidance of placement of the
      catheter with the MR angiography road maps allowed successful embolization,
      balloon occlusion, and transjugular intrahepatic puncture of the portal system.
      Specialized catheters can be tracked in vivo to allow MR guidance in
      intravascular interventional procedures.

PMID- 9015095
TI  - Intestinal malrotation.

PMID- 9015096
TI  - Viral gastroenteritis. Introduction.

PMID- 9015097
TI  - Overview of viral gastroenteritis.
AB  - Diarrheal illnesses in humans have been recognized since antiquity. Such
      illnesses continue to take a great toll of lives, with a disproportionately high
      mortality in infants and young children in developing countries. Bacteriologic
      and parasitologic advances made during the past century led to the discovery of
      the etiology of some of the diarrheal illnesses, but the etiology of the major
      portion remained unknown. It was assumed that viruses caused most of these
      illnesses because: (i) bacteria were recovered from only a small proportion of
      episodes, and (ii) bacteria-free filtrates were found to induce gastroenteritis
      in adult volunteer studies. However, an etiologic agent could not be recovered
      despite the "golden age" of virology in the 1950's and 1960's when tissue culture
      technology enabled the discovery of numerous cultivatable enteric viruses, none
      of which emerged as an important etiologic agent of gastroenteritis. The
      discoveries of the Norwalk virus in 1972, and of rotaviruses in 1973, both
      without the benefit of in vitro tissue culture systems, ushered in a new era in
      the study of the etiology of viral gastroenteritis. The Norwalk virus was found
      to be an important cause of non-bacterial epidemic gastroenteritis in adults and
      older children, and rotaviruses were shown to be the single most important
      etiologic agents of severe diarrheal illnesses of infants and young children in
      both developed and developing countries. With the major advances in the study of
      rotaviruses, there is a high degree of optimism that in the not-too-distant
      future, a rotavirus vaccine will be available. In addition, the recent molecular
      biologic advances in the study of the Norwalk and Norwalk-like viruses, now
      firmly established as caliviviruses, represent a major new horizon in the study
      of these viruses.

PMID- 9015098
TI  - Rotavirus structure: interactions between the structural proteins.
AB  - Structural studies on rotavirus using electron cryomicroscopy and computer image
      analysis have permitted visualization of each shell in the triple-layered
      rotavirus structure. Biochemical results have aided our interpretation of the
      structural organization of these layers and protein interactions seen in the
      three-dimensional structure, and have provided a better understanding of the
      structure-function relationships of the rotavirus structural proteins.

PMID- 9015099
TI  - Structure and function of rotavirus nonstructural protein NSP3.
AB  - The genomes of viruses in the family Reoviridae consist of segmented double
      stranded RNA. There are 10 to 12 segments depending on the genus. The 5' ends and
      the 3' ends of the RNAs present conserved motifs for each virus genus. These
      conserved motifs have been hypothesized to play a role in genomic segment
      assortment during virus morphogenesis. Using a set of monoclonal antibodies we
      have tried to identify rotaviral proteins that bind to RNA during infection in
      cell culture. This methodology takes advantage of being able to label RNA in
      vitro to high specific activity and also of solid phase processing of RNA-protein
      complexes. After cross-linking the RNA to protein in infected cells, protein-RNA
      complexes are precipitated with a specific MAb; then, the RNA in the complex is
      labeled in vitro and the protein or nucleic acid moieties are analyzed by usual
      protocols. This paper describes results using an anti NSP3 MAb. In infected
      cells, we have shown that NSP3 binds to the eleven messenger RNAs, and that a
      sequence from nucleotides 8 to 15 is protected from digestion with RNAse T1 by
      NSP3 in the RNA-protein complex. The availability of recombinant protein NSP3
      expressed in the baculovirus-insect cell system has allowed the sequence
      specificity of NSP3 to be studied in vitro. The minimal sequence recognized by
      NSP3 is GACC. The role of NSP3 in rotavirus replication is discussed based on
      these results and by comparison with other RNA-binding proteins of members of the
      Reoviridae family.

PMID- 9015100
TI  - Genome rearrangements of rotaviruses.
AB  - Rotaviruses (and other members of the Reoviridae family) undergo rearrangements
      of their genomes. This review describes evidence of rearranged genomes in
      rotaviruses. Their structure and functions are reviewed. Possible mechanisms of
      their emergence are discussed, and the significance of genome rearrangements for
      viral evolution is considered.

PMID- 9015101
TI  - Structure and function of rotavirus NSP1.
AB  - Studies on the structure and function of the nonstructural proteins (NSP1-NSP5)
      of rotaviruses are important for dissection of the morphogenesis and replication
      processes of rotavirus. Above all, NSP1, the product of gene 5, has several
      interesting features, such as extreme sequence diversity, a highly conserved
      cysteine-rich region, RNA-binding activity, accumulation on the cytoskeleton, and
      non-random segregation in reassortment. Recently, comparable NSP1 sequence
      analysis has been performed on a number of rotavirus strains from various
      species. Furthermore, characterization of mutants with rearranged NSP1 genes has
      helped to elucidate the structure-function interaction of NSP1. We isolated and
      characterized two interesting mutants which have a large deletion including the
      cysteine-rich region or a nonsense codon at the early portion in the open reading
      frame (ORF) of the NSP1 gene. In this report, we summarize the structure and
      function of NSP1.

PMID- 9015102
TI  - Identification of the minimal replicase and the minimal promoter of (-)-strand
      synthesis, functional in rotavirus RNA replication in vitro.
AB  - An in vitro replication system supporting the initiation and synthesis of
      complete rotavirus (-)-strands on (+)-strand template RNA (Chen et al., J Virol
      68: 7030, 1994) was used to examine several parameters related to rotavirus RNA
      replication. Coexpression of VP1/2/3 in all possible combinations from
      baculovirus vectors revealed: [i] Virus-like particles (VLPs) were formed only if
      VP2 was present, and [ii] VP1/2 and VP1/2/3 VLPs had replicase activity in the in
      vitro system whereas VP2/3 and VP2 VLPs did not. Thus, the minimal replicase is
      composed of VP1 and VP2 and replicase activity is associated with VP1. In vitro
      replication reactions, using T7 transcripts of porcine rotavirus OSU genome
      segment 9 as reporter template, were performed to map cis-acting elements that
      regulate replication. Internal deletions and terminal truncations of the reporter
      RNA localized a replication signal, conferring full template activity, to the 5'
      terminal 27 nucleotides (nt 1-27) and the 3'-terminal 26 nucleotides (nt 1037
      1062). Further analysis showed that a minimal promoter of (-)-strand synthesis
      was contained in the 3'-terminal 7 nucleotides (nt 1056-1062); the sequence
      conserved at the 3'-terminus of all rotavirus genes. Hybrid constructs with this
      promoter had minimal, but detectable, template activity. This result indicated
      that upstream sequences between nucleotides 1037-1055 positively regulate the
      activity of the minimal promoter.

PMID- 9015104
TI  - A hypothesis about the mechanism of assembly of double-shelled rotavirus
      particles.
AB  - During double-shelled (ds) particle assembly, subviral particles [possibly single
      shelled (ss) particles] acquire the outer capsid protein during their transport
      across the endoplasmic reticulum (ER) membrane by an exocytosis-like process,
      probably by a fusion-like mechanism. Fine reticular material is observed around
      the junction area between virus particles and the ER membrane on the cytoplasmic
      side of projecting ss particles, suggesting this is the site of assembly of ds
      particles. It is assumed that the reticular material may correspond to the hetero
      oligometric complexes consisting of the non-structural glycoprotein NSP4, the
      structural proteins VP4 and VP7, and that both VP7 and VP4 may fold onto ss
      particles as a complex. On the other hand, the budding process simply serves as a
      vehicle to transport ss particles from the cytoplasm to the ER lumen. Thus, it is
      assumed that the production of protein complexes may be indispensable for virion
      assembly, in which NSP4 regulates VP4 folding as an ER chaperone and also the
      exocytosis-like or fusion-like transport systems through the ER membrane.

PMID- 9015103
TI  - Rotavirus protein expression is important for virus assembly and pathogenesis.
AB  - Rotaviruses have a unique morphogenesis in which particles obtain a transient
      membrane-envelope as newly made subviral particles bud into the endoplasmic
      reticulum (ER). This process is mediated by a viral nonstructural glycoprotein,
      NSP4. We have found that NSP4 has pleiotropic properties that became evident
      following expression of this protein in eukaryotic cells. NSP4 expressed in
      insect cells bound double-layered rotavirus particles in a manner similar to
      receptor-ligand interactions and this interaction is thought to trigger the
      particle budding process. Expression of NSP4 in insect cells also increases
      intracellular calcium ([Ca2+]i) levels and this effect may explain the toxicity
      of this protein in eukaryotic cells. Increases in [Ca2+]i levels in insect cells
      also are observed following exogenous addition to cells of purified NSP4 or of a
      synthetic peptide of NSP4. Experiments to determine the mechanism by which NSP4
      causes an increase in [Ca2+]i showed that Ca2+ is released from a subset of the
      thapsigargin-sensitive store [endoplasmic reticulum (ER)]. However, exogenously
      added and endogenously expressed NSP4 use different mechanisms to alter the Ca2+
      permeability of the ER membrane. We hypothesize that NSP4-mediated changes in ER
      membrane permeability trigger viral budding into the lumen of the ER, and
      eventually induce cell death and release of virus particles from infected cells.
      We also propose that release of NSP4 following cell lysis and the concomitant
      stimulation of a Ca2+ signal transduction pathway in neighboring cells
      contributes to altered ion transport in intestinal epithelium resulting in
      diarrheal disease.

PMID- 9015105
TI  - Development of rotavirus molecular epidemiology: electropherotyping.
AB  - Early in the era of rotavirology it was realized that the characteristic patterns
      of bands produced in polyacrylamide gels following electrophoresis of genomic
      dsRNA were useful for checking the identity of rotavirus isolates. However it was
      Romilio Espejo who first proposed the use of this technique for epidemiology,
      although most others did not take the suggestion seriously because the technique
      was then rather specialized and RNA staining methods were not very sensitive.
      Using samples collected by Ruth Bishop in Melbourne following the original
      identification of human rotaviruses, Sue Rodger recorded the "electropherotypes"
      of all samples available to 1979 and painstakingly compared them, side by side
      (since minor variations in conditions, especially temperature, alter the relative
      migration distances of dsRNA bands). These efforts produced the first
      longitudinal, extensive study of human rotavirus strain variation. Since then,
      technical improvements have greatly increased the sensitivity of the procedures,
      and electropherotyping has been recognized as a powerful and economical method
      for epidemiological studies of rotaviruses.

PMID- 9015106
TI  - Molecular epidemiology of human rotaviruses: genogrouping by RNA-RNA
      hybridization.
AB  - RNA-RNA hybridization performed under high stringency conditions allows rotavirus
      isolates to be grouped together based on the overall similarity of their genomic
      RNA constellation. Classification by this scheme has been termed "genogrouping".
      Genogrouping has advanced molecular epidemiology of human rotaviruses. Major
      observations include (i) Interspecies transmission occurs in nature and (ii)
      Intergenogroup reassortment occurs in nature with or without exchange of serotype
      determining genes. Genogrouping is a particularly valuable asset for determining
      the gene constellation of unusual rotavirus isolates.

PMID- 9015107
TI  - Classification of rotavirus VP4 and VP7 serotypes.
AB  - Rotaviruses, members of the Reoviridae family, are major etiologic agents of
      acute nonbacterial gastroenteritis of the young in a wide variety of mammalian
      and avian species, including humans. The need for effective immunoprophylaxis
      against rotaviral gastroenteritis has stimulated interest in the biochemical,
      molecular, genetic, and clinical aspects of these agents with the aim of
      developing safe and effective vaccines. Because neutralizing antibodies appear to
      play an important role in protection against many viral diseases, rotavirus
      antigens that induce neutralizing antibodies have played a central role in
      research and development of a rotavirus vaccine. The VP7 glycoprotein and VP4
      spike protein that constitute the outer capsid of a complete rotavirus particle
      have been shown to be independent neutralization antigens. Since type specificity
      of the outer capsid proteins of a rotavirus appears to play an important role in
      protection against disease in experimental animal models, continued efforts have
      been made for classification and typing of neutralization specificities on the
      VP7 or VP4 capsid protein. Based on a criterion of > 20-fold differences between
      the homologous and heterologous reciprocal neutralizing antibody titers, fourteen
      VP7 (G) serotypes have been established. Studies are underway to characterize and
      classify the VP4 (P) serotypes among the strains that exhibit the fourteen
      different G serotypes. Attempts to classify the VP4 serotypes based on the same
      criterion (i.e., > 20-fold antibody differences) that is applied to
      classification of VP7 serotypes are in progress. This standard of > 20-fold
      antibody differences can be applied with hyperimmune serum raised to a
      reassortant possessing the VP4 encoding gene (and an unrelated VP7 encoding
      gene). Genotypes can provide leads towards classification but the serotype of a
      strain should be based on neutralization.

PMID- 9015108
TI  - VP4 and VP7 typing using monoclonal antibodies.
AB  - Both rotavirus outer capsid proteins, VP4 and VP7, elicit neutralizing
      antibodies. Neutralizing mouse monoclonal antibodies (N-MAbs) to VP7 are easily
      derived and have been used widely and successfully to serotype both stool-derived
      and culture-adapted rotaviruses by enzyme immunoassay (EIA). Generally,
      approximately 70% of rotaviruses in stool samples are typable by VP7 EIA, an
      inexpensive and practical method. Variations in antigenic regions between strains
      within human rotavirus serotypes 1, 2, 4, and 9 have been recorded. These have
      been termed monotypes because they are detected with N-MAbs. The molecular basis
      for monotypes has been determined by mapping mutations selected in N-MAb
      resistant antigenic variants, and by sequence analysis of the gene encoding VP7
      in newly recognized monotypes. Antigenic regions A, B and C in VP7 are involved.
      In order to detect all members of a particular VP7 serotype, it is necessary to
      type with a panel of N-MAbs specific for that serotype. N-MAbs to VP4 of human
      rotavirus are difficult to raise and few have proven suitable for VP4 serotyping
      by EIA. The specificity of the assay for each P type is highest when the VP7
      serotype specificity of the capture antiserum is matched to the G type of the
      rotavirus in the test sample. The VP4 EIA gives similar typing rates to the VP7
      typing EIA. N-MAbs directed to VP8, the smaller subunit of VP4 generated by
      proteolytic cleavage, are more likely to show serotype specificity. Some N-MAbs
      that select mutations in the putative fusion region of VP5, the larger subunit of
      VP4, show cross-reactivity with extracts of normal, uninfected MA 104 cells and
      with fetal bovine serum. These N-MAbs also give elevated EIA OD readings with
      rotavirus-positive, but previously non-reactive fecal samples which have been
      frozen and thawed repeatedly. Overall, VP8-reactive N-MAbs appear most suitable
      for VP4 typing by EIA.

PMID- 9015109
TI  - Natural history of human rotavirus infection.
AB  - Rotavirus infections occur repeatedly in humans from birth to old age. Most are
      asymptomatic or are associated with mild enteric symptoms. Infection in young
      children can be accompanied by severe life-threatening diarrhea, most commonly
      after primary infection. Annual childhood morbidity rates for severe diarrhea are
      similar worldwide. Mortality rates are low in developed countries but approach
      1,000,000 annually in young children in developing countries. Rotaviruses can be
      classified into Groups A-E according to antigenic groups on VP6, the major capsid
      antigen. Only Group A,B and C rotaviruses have been shown to infect humans, and
      most human rotavirus disease is caused by Group A viruses. These are further
      classified into G and P types based on identification of antigens on the outer
      capsid proteins VP7 and VP4 respectively. Most severe infections in young
      children are caused by serotypes G1-4, and during the last two decades, G1
      infections appear to have predominated worldwide. In general the more densely
      populated countries show the most complex patterns of occurrence of serotypes.
      Clinical rotavirus disease can be accompanied by shedding of > 10(12) rotavirus
      particles/gm feces. The virus is highly infectious and appears to retain
      infectivity over many months. In temperate climates, disease is most common
      during the colder months, when it is likely that rapid spread within families and
      communities occurs. Nosocomial infections are frequent, and rotaviruses can
      become endemic within obstetric hospital nurseries for the newborn. Few (if any)
      human rotavirus infections appear to be zoonoses, even though Group A rotaviruses
      are widespread in the young of all mammalian species. However infection of humans
      with reassortant rotavirus strains derived from human-animal sources can occur.
      The extent to which this contributes to new epidemic strains within particular
      countries (or worldwide) remains to be determined.

PMID- 9015110
TI  - Protective immunity against group A rotavirus infection and illness in infants.
AB  - Understanding of the protective effect provided by natural rotavirus infections
      against subsequent rotavirus infections is required for evaluating vaccine
      development programs. Prior studies of the protective efficacy of natural
      infections and correlates of natural protection are reviewed and results from
      several studies presented only in abstract form are summarized to provide a
      current assessment of knowledge in this area. Six cohort studies have reported
      rates for the protective efficacy of a natural rotavirus infection against
      subsequent infection, diarrhea, or severe diarrhea. These efficacy estimates
      ranged from 0 to 100% and are not directly comparable because of differences in
      methodology and population monitored. Results from other study designs also have
      been confusing, until recently. Recent studies have identified immunologic
      correlates of protection and studies from a cohort of intensely monitored Mexican
      children promise to provide a comprehensive assessment of the strength of the
      protective effect of natural rotavirus infection.

PMID- 9015111
TI  - Rotavirus immunity in the mouse.
AB  - Naturally attenuated animal rotaviruses have been tested as antirotavirus
      vaccines with moderate success. The development of improved vaccines will rely on
      our understanding of the immune mechanism that mediate clearance and protection
      from rotaviral reinfection. The mouse model of rotavirus infection is a versatile
      tool for studying these mechanisms: mice have a relative low cost and there is a
      rapidly increasing number of immunological reagents to study rotavirus
      immunology. This review covers recent data on the mouse model of rotavirus
      infection. We show that both effector arms of the immune system (CD8 + T cells
      and B cells) mediate anti-rotavirus effects in vivo.

PMID- 9015112
TI  - The gnotobiotic piglet as a model for studies of disease pathogenesis and
      immunity to human rotaviruses.
AB  - Gnotobiotic piglets serve as a useful animal model for studies of human rotavirus
      infections, including disease pathogenesis and immunity. An advantage of piglets
      over laboratory animal models is their prolonged susceptibility to human
      rotavirus-induced disease, permitting cross-protection studies and an analysis of
      active immunity. Major advances in rotavirus research resulting from gnotobiotic
      piglet studies include: 1) the adaptation of the first human rotavirus to cell
      culture after passage and amplification in piglets; 2) delineation of the
      independent roles of the two rotavirus outer capsid proteins (VP4 and VP7) in
      induction of neutralizing antibodies and cross-protection; and 3) recognition of
      a potential role for a nonstructural protein (NSP4) in addition to VP4 and VP7,
      in rotavirus virulence. Current studies of the pathogenesis of group A human
      rotavirus infections in gnotobiotic piglets in our laboratory have confirmed that
      villous atrophy is induced in piglets given virulent but not cell culture
      attenuated human rotavirus (G1, P1A, Wa strain) and have revealed that factors
      other than villous atrophy may contribute to the early diarrhea induced. A
      comprehensive examination of these factors, including a proposed role for NSP4 in
      viral-induced cytopathology, may reveal new mechanisms for induction of viral
      diarrhea. Finally, to facilitate and improve rotavirus vaccination strategies,
      our current emphasis is on the identification of correlates of protective active
      immunity in the piglet model of human rotavirus-induced diarrhea. Comparison of
      cell-mediated and antibody immune responses induced by infection with a virulent
      human rotavirus (to mimic host response to natural infection) with those induced
      by a live attenuated human rotavirus (to mimic attenuated oral vaccines) in the
      context of homotypic protection has permitted an analysis of correlates of
      protective immunity. Results of these studies have indicated that the magnitude
      of the immune response is greatest in lymphoid tissues adjacent to the local site
      of viral replication (small intestine). Secondly, there was a direct correlation
      between the degree of protection induced and the level of the intestinal immune
      response, with significantly higher local immune responses and complete
      protection induced only after primary exposure to virulent human rotavirus. These
      studies thus have established basic parameters related to immune protection in
      the piglet model of human rotavirus-induced disease, verifying the usefulness of
      this model to examine new strategies for the design and improvement of human
      rotavirus vaccines.

PMID- 9015113
TI  - Jennerian and modified Jennerian approach to vaccination against rotavirus
      diarrhea using a quadrivalent rhesus rotavirus (RRV) and human-RRV reassortant
      vaccine.
AB  - Rotaviruses are the single most important cause of severe diarrhea of infants and
      young children world-wide. Deaths from rotavirus diarrhea occur infrequently in
      developed countries; however, in developing countries, rotaviruses are estimated
      to cause over 870000 deaths in the under five-year age group. There is,
      therefore, a vital need for a vaccine to prevent severe rotavirus diarrhea in
      infants and young children. The most extensively evaluated strategy for rotavirus
      vaccination has been the "Jennerian" approach in which an antigenically related
      rotavirus strain from an animal host (bovine or simian [rhesus monkey]) is used
      as the immunogen to induce protection against the four epidemiologically
      important group A human rotavirus serotypes. These orally administered vaccines
      were safe and immunogenic but had only limited success because serotype-specific
      immunity was not induced consistently in the under six-month age group.
      Therefore, a modified "Jennerian" approach was adopted with the goal of attaining
      broader antigenic coverage. In this approach four serotypes are combined to form
      a quadrivalent vaccine comprised of (i) rhesus rotavirus (RRV) which provides
      coverage for VP7 serotype 3, and (ii) three human-RRV reassortants each with ten
      RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4
      specificity. This modified "Jennerian" approach appears to be quite promising in
      preventing severe diarrhea in field trials. However, if this approach fails to
      yield an optimal level of protection consistently, additional modified
      "Jennerian" strategic, are under development that consider not only human
      rotavirus VP7 but also human rotavirus VP4, the other outer capsid protein. In
      addition, a non-"Jennerian" approach includes the development of cold-adapted
      human rotavirus strains or cold-adapted human rotavirus reassortants as vaccine
      candidates.

PMID- 9015114
TI  - Trials of oral bovine and rhesus rotavirus vaccines in Finland: a historical
      account and present status.
AB  - Live oral rotavirus vaccine strain RIT 4237, derived from group A bovine
      rotavirus NCDV, was given to human volunteers in Tampere, Finland in 1982.
      Efficacy studies of this vaccine in 6-12 month-old children gave results
      characteristic of the performance of oral rotavirus vaccines in general: 58%
      protective efficacy against any rotavirus gastroenteritis and 82% against
      "clinically significant" gastroenteritis. Four trials of RIT 4237 bovine
      rotavirus vaccine, one trial of group A RRV-1 rhesus rotavirus vaccine, and one
      trial of rhesus-human reassortant rotavirus vaccines D x RRV and DS1 x RRV were
      carried out between 1983-1989. A meta-analysis of the protective efficacy of
      these vaccines indicated a 67% (95% C.I. 55-77%) efficacy against moderately
      severe rotavirus disease and an 81% (95% C.I. 60-91%) efficacy against severe
      rotavirus disease. There was no apparent difference between bovine and rhesus
      based rotavirus vaccines in the protective efficacy against severe rotavirus
      gastroenteritis. Problems associated with the use of any oral rotavirus vaccine
      include acid lability of the vaccine virus, which requires buffering, and a
      slight but significant interference of oral poliovirus vaccine with the uptake of
      rotavirus vaccine. In the near future, oral heterologous rotavirus vaccines may
      be available for prevention of severe rotavirus gastroenteritis.

PMID- 9015115
TI  - WC3 reassortant vaccines in children.
AB  - Bovine rotavirus strain WC3 (P7[5], G6) administered at the 12th passage level
      was well tolerated clinically in infants and efficiently induced serum virus
      neutralizing antibody (VNA) with bovine rotavirus G6 specificity. The protective
      efficacy of WC3 vaccine against all rotavirus disease was inconsistent, varying
      in four separate trials from 76% to 0%; some selective protection against severe
      disease was seen in all trials. WC3 reassortants containing the gene for an
      individual human rotavirus VP7 (G) or VP4 (P) surface antigen were also well
      tolerated, but preferentially induced VNA to the WC3 parent. Efficacy trials of
      human G1 VP7 reassortant WI79-9 (P7[5], G1) consistently led to > 60% protection
      against all rotavirus disease. A quadrivalent WC3 reassortant vaccine was
      developed to contain four separate monovalent reassortants expressing human
      rotaviruses surface proteins G1, G2, G3, and P1A [8] respectively. In a
      multicenter trial including 439 infants, this vaccine induced 67.1% protection
      against all rotavirus disease (defined as positive for rotavirus antigen by ELISA
      only [p = < 0.001]) and 72.6% protection when the standard for rotavirus
      diagnosis was a positive test of stool for both rotavirus antigen by ELISA and
      rotavirus RNA by electropherotype analysis (p = < 0.001). In this trial, episodes
      of the most severe rotavirus disease (clinical severity score > 16.0 eight cases)
      occurred only in placebo recipients.

PMID- 9015116
TI  - Rotavirus subunit vaccines.
AB  - We evaluated rotavirus subunit vaccines for use in humans and animals. Insect
      cells were co-infected with combinations of individual baculovirus recombinants
      expressing human, bovine or simian rotavirus VP2, VP4, VP6 or VP7 to produce
      virus-like particles (VLPs). To determine whether immunization with VLPs could
      induce active protective immunity, VLPs were administered parenterally to
      rabbits, and the immune response and protection from rabbit ALA rotavirus
      challenge were evaluated. Complete or partial protection was attained, showing
      that parenteral immunization with VLPs induces active protective immunity. We
      also examined whether heterotypic immune responses could be induced with a
      limited number of broadly reactive VP7 proteins or with chimeric particles
      (multiple VP7 types on individual particles). The feasibility of this approach
      was determined by immunizing mice with VLPs containing a G3 VP7 or G1 VP7 and
      chimeric G1/G3 VLPs. Broadly reactive neutralizing antibody was induced by the G1
      VLPs. VLPs also have been successfully used to boost lactogenic (colostral and
      milk) immunity in dairy cows. Taken together, these results show that VLPs can be
      effective immunogens in rabbits, mice and dairy cattle when administered
      parenterally, a limited number of VLPs may be sufficient to produce a broadly
      protective vaccine, and G3 VLPs may serve as an effective subunit vaccine for use
      in bovines.

PMID- 9015117
TI  - DNA vaccines against rotavirus infections.
AB  - Plasmid DNA vaccines encoding for murine rotaviral proteins VP4, VP6, and VP7
      were tested in adult BALB/c mice for their ability to induce immune responses and
      provide protection against rotavirus challenge. Serum antibodies were measured by
      virus neutralization and by ELISA. Cellular immunity was assessed by measuring
      cytotoxic T cell (CTL) responses. The vaccines were administered by inoculation
      into cells of the epidermis with an Accell gene gun (Auragen, Inc., Middleton,
      WI, USA). Each of the three vaccines elicited rotavirus-specific serum antibodies
      as measured by ELISA. Virus neutralizing antibodies were detected in mice
      receiving DNA vaccines encoding for VP4 and VP7, but not in those which received
      the plasmid encoding for VP6. Vaccines encoding for VP4, VP6, or VP7 generated
      virus-specific CTL responses in recipient mice. Efficacy of the vaccines was
      determined by challenge with homotypic rotaviruses. Each of the three vaccines
      was effective in protecting mice against infection after rotavirus (100 ID50)
      challenge. Significant reductions (p < 0.0002, analysis of variance) in viral
      excretion measured over a 9 day period were seen in mice receiving the DNA
      vaccines compared with mice that received control plasmids.

PMID- 9015118
TI  - Prophylaxis of rotavirus gastroenteritis using immunoglobulin.
AB  - Oral inoculation of the human group A rotavirus MO strain (G serotype 3) into 5
      day-old BALB/c mice causes gastroenteritis characterized by diarrhea. Using this
      small animal model, passive protection of suckling mice against human rotavirus
      infection was achieved with the use of immunoglobulin (IgY) from the yolks of
      eggs of rotavirus-immunized hens. When IgY against the rotavirus strain homotypic
      with the challenge virus (MO strain) was administered to mice, complete
      protection was achieved. After immunizing 8-month old pregnant Holstein cows with
      human rotavirus MO strain, colostrum containing neutralizing antibody to four
      different G serotypes of human rotavirus, designated Rota colostrum, was
      obtained. Rota colostrum completely protected suckling mice against rotavirus
      infection, and purified IgG obtained from Rota colostrum protected against
      infection with the homologous virus. After randomly grouping 20 infants from a
      baby care center, 10 infants received 20 ml of Rota colostrum for 2 weeks and 10
      control infants received none. Rotavirus-associated diarrhea developed in 7 of
      the 10 infants in the control group. None of the three infants in the group daily
      receiving the Rota colostrum had such symptoms, and one of three infants in the
      group receiving treatment, every other day developed rotavirus-induced diarrhea.
      Oral administration of Rota colostrum seems to be an effective and safe means of
      preventing diarrhea caused by human rotavirus infection. Recently, the immunized
      cows were boosted by reinjection of 4 serotypes of human rotavirus into a
      superficial cervical lymph node two weeks after delivery, resulting in mass
      production of cow's milk containing a high-titered antibody to human rotavirus.
      Therefore, the hyperimmune cow's milk is a candidate for a "physiologically
      functional food" in Japan.

PMID- 9015119
TI  - Historical background and classification of caliciviruses and astroviruses.
AB  - Infections caused by caliciviruses, i.e., vesicular exanthema virus of swine were
      recognised as a major cause of economic loss in the 1930s. However, it was not
      until the application of electronmicroscopy in the 1970s that caliciviruses and
      astroviruses were recognised and proven to be a cause of diarrhoea and vomiting.
      The following review briefly describes the steps which have led to the
      development of diagnostic tests and enabled the characterization of several
      members of the Caliciviridae and Astroviridae. In the past five years this has
      culminated in the sequencing of their genomes and the expression of viral
      proteins. This in turn has led to the development of improved diagnostic tests
      e.g., RT-PCR and enzyme immunoassays, and may pave the way towards producing
      effective vaccines in the future.

PMID- 9015120
TI  - Structure of Norwalk virus.
AB  - Norwalk virus is the major cause of epidemic viral gastroenteritis of humans.
      Attempts to grow this virus in laboratory cell lines have been unsuccessful.
      However, the Norwalk virus capsid protein, when expressed in insect cells
      infected with a recombinant baculovirus, spontaneously assembles into virus-like
      particles. We have determined the 3-dimensional structure of baculovirus
      expressed Norwalk virus using electron cryomicroscopy and computer image
      reconstruction to a resolution of approximately 22 A. These particles, having a
      diameter of 380 A exhibit T = 3 icosahedral symmetry. The 3-dimensional structure
      is composed of 90 dimers of the 58000 molecular weight (58 K) capsid protein,
      each of which forms an arch-like capsomere. The structure of the protein subunit
      is modular with three distinct domains. The distal globular domain that appears
      bilobed is connected to the lower shell domain by a central stem-like domain. We
      also have been able to grow crystals of the baculovirus-expressed Norwalk virus
      particles suitable for high resolution X-ray crystallography.

PMID- 9015121
TI  - Recombinant Norwalk virus-like particles as an oral vaccine.
AB  - Viruses that infect cells in the gastrointestinal tract are well suited for
      examining the immune response to oral delivery of antigen and for exploring the
      advantages and pitfalls of oral vaccines. Norwalk virus (NV) (family
      Caliciviridae, genus Calicivirus) causes acute gastroenteritis in all age groups.
      The NV capsid is composed of 180 copies of a single 58000 molecular weight
      protein which spontaneously forms virus-like particles (VLPs) that can be
      purified in extremely high yields (22 mg per 300 ml culture) when produced using
      the baculovirus expression system. We are testing the potential of these
      recombinant NV (rNV) particles for use as an oral vaccine by administering them
      to mice and volunteers. Mice were orally inoculated four times with rNV particles
      in concentrations ranging from 5 to 500 micrograms in the absence of adjuvant or
      from 5 to 200 micrograms with 10 micrograms of cholera toxin. Serum IgG and fecal
      IgA immune responses were monitored. rNV particles were found to be immunogenic
      when orally given to mice with or without adjuvant. These particles also were
      safe and immunogenic when orally given to volunteers. These studies show that rNV
      particles are an excellent model to test the oral delivery of mucosal immunogens
      in general, and that rNV particles are ideal candidates for vaccine development
      in particular.

PMID- 9015122
TI  - Genetic and antigenic diversity of human caliciviruses (HuCVs) using RT-PCR and
      new EIAs.
AB  - RT-PCR using primers from conserved regions of calicivirus genomes, followed by
      sequencing, permits characterization of genetic variation within the family. EIAs
      based on baculovirus-expressed viral capsid proteins and hyperimmune antisera
      against the capsid proteins were developed to detect HuCV antigens and
      antibodies. Serologic surveys using recombinant Norwalk virus (rNV) and
      recombinant Mexico virus (rMX, a SMA-like virus) EIAs showed that infections by
      HuCVs are common and that children acquire antibodies to HuCVs at an early age in
      both developed and developing countries. Three HuCV genogroups have been
      described that are represented by Norwalk virus (NV), Snow Mountain agent (SMA),
      and Sapporo virus, although recently accumulated sequences of HuCV strains
      indicate these genogroups can be further divided. These genogroups also
      correspond to distinct antigenic groups based on the results of the recombinant
      EIAs. The three genogroups co-circulate and have a worldwide distribution,
      although the SMA genogroup seems to be predominant currently. Application of
      these new assays for further characterization of the genetic and antigenic
      properties of HuCVs remains an important task for HuCV research.

PMID- 9015123
TI  - The epidemiology of human calicivirus/Sapporo/82/Japan.
AB  - Based on genome analysis of the RNA-dependent RNA polymerase region, it has been
      proposed that human caliciviruses (HuCV) can be classified into at least three
      genogroups: genogroup I is represented by Norwalk virus (NV), genogroup II by
      Snow Mountain agent (SMA) and genogroup III by HuCV/Sapporo/82/Japan
      (HuCV/Sa/82/J) virus. HuCV/Sa/82/J strain is genetically unique and more closely
      related to animal caliciviruses than are other known HuCVs, such as NV and SMA.
      HuCV/Sa/82/J strain was detected in four outbreaks of HuCV gastroenteritis
      occurring between 1977 and 1982 in an infant home in Sapporo. The HuCVs detected
      from these four outbreaks all showed a typical "Star of David" configuration by
      electron microscopy (EM), and they were identical antigenically and genetically.
      This strain has also been detected in other prefectures in Japan, as well as in
      the USA, UK, Saudi Arabia and Kenya. Seroepidemiological studies have shown a
      worldwide distribution of this virus, including Japan, USA, UK, Southeast Asia,
      Canada, China and Kenya. This virus has been circulating in Sapporo for at least
      19 years (1977-1995). HuCV/Sa/82/J strain is thought to be one of the common
      causes of viral gastroenteritis worldwide. The HuCV/Sa/82/J strain has been
      detected mainly in infants. Age-related prevalence of antibody to this strain
      also shows that infections commonly occur in children less than 5 years old,
      although viruses in the NV and SMA genogroups commonly infect adults. The pattern
      of acquisition of antibodies to strain HuCV/Sa/82/J is similar to that of other
      common viral infections. HuCV/Sa/82/J strain is unique virologically and
      clinically among caliciviruses.

PMID- 9015124
TI  - Reverse transcription-polymerase chain reaction detection and sequence analysis
      of small round-structured viruses in Japan.
AB  - Between 1985 and 1995, mass outbreaks of acute gastroenteritis caused by small
      round-structured virus (SRSV), occurred in eight prefectures in Japan. Fecal
      samples from 59 patients ill during these outbreaks were recently examined in our
      laboratory by electron microscopy (EM) and by reverse transcription-polymerase
      chain reaction (RT-PCR). For RT-PCR, we prepared two sets of primers, a set
      corresponding to the polymerase region of open reading frame 1 (ORF-1) and a set
      corresponding to the capsid region of ORF-2 of Norwalk virus (NV). The SRSV
      nucleic acid detection rate with these primers was more than double that achieved
      with EM. Most samples found by EM to contain virus particles were also positive
      by PCR. When the two sets of primers were used separately, the virus detection
      rate differed depending on the primer used, suggesting that the viral strains
      examined were not genetically not homogeneous. We then selected nine strains of
      the virus, cloned their PCR products and analyzed their base sequences. The base
      sequences of these strains were compared with those of reference strains
      including prototype NV and Snow Mountain agent (SMA). This comparison yielded the
      following findings: (1) SRSVs that cause mass outbreaks of gastroenteritis in
      Japan are genetically variable; (2) SRSV strains that are genetically similar to
      SMA and SRSV-OTH 25/89/J(OTH25) are dominant in Japan, but strains similar to NV
      are also present in this country; and (3) a strain (MI1/94) which is genetically
      identical to Southampton virus (SHV) was detected. Detection of SRSV using
      sensitive RT-PCR and analysis of the sequences of the amplification products
      seems to provide a useful means of studying the molecular epidemiology of SRSV.

PMID- 9015125
TI  - The molecular biology of astroviruses.
AB  - Astroviruses (genus Astrovirus) are assigned to a newly established virus family,
      the Astroviridae. The molecular biology of these agents reveals many features
      unique amongst the non-enveloped animal viruses and resembles that of members of
      certain plant virus families. In particular, their possession of a serine
      protease and use of ribosomal frameshifting to express the RNA polymerase are
      similar to the luteoviruses. Many aspects of the astrovirus replication strategy
      are still unclear, but replication may involve a nuclear step and non-structural
      proteins may influence host cell range.

PMID- 9015126
TI  - The changing epidemiology of astrovirus-associated gastroenteritis: a review.
AB  - Our understanding of the epidemiology of astrovirus-associated gastroenteritis
      has changed markedly with each improvement in detection method. In early surveys
      based on electronmicroscopy (EM), astroviruses appeared to be a rare cause of
      gastroenteritis, being found in fewer than 1% of children with diarrhea, usually
      in small outbreaks of disease and primarily during the winter season. The
      development and use of monoclonal antibodies and enzyme immunoassays (EIA) to
      detect astroviruses led to reports of a higher prevalence (2.5%-9%) of astrovirus
      infection among patients hospitalized with diarrhea. Astroviruses appeared second
      only to rotaviruses as a cause of hospitalization for childhood viral
      gastroenteritis. Studies based on EIA detection of astroviruses indicate that
      astroviruses are common causes of diarrhea in children worldwide, and that most
      children are infected during their first two years of life. The elderly and the
      immunocompromised represent high-risk groups as well. The observations that
      newborns monitored prospectively rarely have repeat disease and that the rate of
      detection decreases with increasing age suggest that immunity to astroviruses, as
      immunity to rotaviruses, may develop early in life. The cloning and sequencing of
      astroviruses have led to more sensitive assays to detect the viruses by reverse
      transcription, polymerase chain reaction (RT-PCR). Application of RT-PCR for
      detection of astroviruses in children in day-care centers showed a marked
      increase in the detected prevalence of astrovirus-associated diarrhea, the rate
      of asymptomatic infection, and the duration of shedding of virus among those
      infected, when compared with studies that used other methods. As with
      rotaviruses, neither the mode of transmission nor the reservoir of astrovirus
      infection has been identified. Both immune and molecular-based assays to detect
      astrovirus serotypes indicate that serotype 1 is most common worldwide, although
      the predominant serotypes may vary by region and time. In the absence of obvious
      strategies to prevent astrovirus-associated diarrhea, vaccines might be
      considered if further studies establish that the disease burden would render such
      a vaccine cost-effective.

PMID- 9015128
TI  - 5th Annual meeting of the Israel Society for Neurosciences. Eilat, Israel, 1-4
      December 1996. Abstracts.

PMID- 9015127
TI  - Structural features unique to enteric adenoviruses.
AB  - Enteric adenoviruses are important agents of pediatric gastroenteritis.
      Characterization of monoclonal antibodies against human adenovirus 41 (h-41)
      identified an epitope of interest on protein VI, an internal virion protein. The
      epitope is common to enteric adenoviruses (subgenus A: h-12, h-18, h-31 and
      subgenus F: h-40, h-41) but is not shared by non-enteric serotypes (subgenera B,
      C, D or E). By expressing random oligonucleotide fragments of the protein VI gene
      as T7 gene 10 fusion proteins in the pTope vector (Novagen), the epitope was
      mapped within the central domain of protein VI, to the region corresponding to aa
      114-125 of the Ad2 protein. Identification of this epitope reflects the close
      evolutionary relationship of subgenus A and subgenus F adenoviruses and draws
      attention to structural features of enteric adenoviruses as potential
      determinants of tropism. Furthermore, this epitope may be valuable for
      identification of enteric adenoviruses in clinical specimens.

PMID- 9015130
TI  - Lead-induced changes in ovarian follicular development and maturation in mice.
AB  - Lead, a potent reproductive toxicant in humans and experimental animals, was used
      to detect the morphological basis of ovarian toxicity in mice by counting the
      various stages of follicular development using different doses of lead acetate
      (0, 2, 4 or 8 mg/kg/d) for 60 d (5 d/wk) by oral gavage. Our results revealed
      that while small and medium follicles were significantly affected even at the
      lowest dose (2 mg), the large follicles were affected mostly at the highest dose.
      Atresia even in the medium follicles reflected the extent of damage caused by
      lead. These findings correlated well with increased blood lead levels. Therefore,
      lead seems to affect the follicular development and maturation, if mice are,
      exposed to sufficiently high concentrations of metal through the oral route.

PMID- 9015129
TI  - Biochemical and molecular changes at the cellular level in response to exposure
      to environmental estrogen-like chemicals.
AB  - Estrogen-like chemicals are unique compared to nonestrogenic xenobiotics, because
      in addition to their chemical properties, the estrogenic property of these
      compounds allows them to act like sex hormones. Whether weak or strong, the
      estrogenic response of a chemical, if not overcome, will add extra estrogenic
      burden to the system. At elevated doses, natural estrogens and environmental
      estrogen-like chemicals are known to produce adverse effects. The source of extra
      or elevated concentration of estrogen could be either endogenous or exogenous.
      The potential of exposure for humans and animals to environmental estrogen-like
      chemicals is high. Only a limited number of estrogen-like compounds, such as
      diethylstilbestrol (DES), bisphenol A, nonylphenol, polychlorinated biphenyls
      (PCBs), and dichlorodiphenyltrichloroethane (DDT), have been used to assess the
      biochemical and molecular changes at the cellular level. Among them, DES is the
      most extensively studied estrogen-like chemical, and therefore this article is
      focused mainly on DES-related observations. In addition to estrogenic effects,
      environmental estrogen-like chemicals produce multiple and multitype genetic
      and/or nongenetic hits. Exposure of Syrian hamsters to stilbene estrogen (DES)
      produces several changes in the nuclei of target organ for carcinogenesis
      (kidney): (1) Products of nuclear redox reactions of DES modify transcription
      regulating proteins and DNA; (2) transcription is inhibited; (3) tyrosine
      phosphorylation of nuclear proteins, including RNA polymerase II, p53, and
      nuclear insulin-like growth factor-1 receptor, is altered; and (4) DNA repair
      gene DNA polymerase beta transcripts are decreased and mutated. Exposure of Noble
      rats to DES also produces several changes in the mammary gland: proliferative
      activity is drastically altered; the cell cycle of mammary epithelial cells is
      perturbed; telomeric length is attenuated; etc. It appears that some other
      estrogenic compounds, such as bisphenol A and nonylphenol, may also follow a
      similar pattern of effects to DES, because we have recently shown that these
      compounds alter cell cycle kinetics, produce telomeric associations, and produce
      chromosomal aberrations. Like DES, bisphenol A after metabolic activation is
      capable of binding to DNA. However, it should be noted that a particular or
      multitype hit(s) will depend upon the nature of the environmental estrogen-like
      chemical. The role of individual attack leading to a particular change is not
      clear at this stage. Consequences of these multitypes of attack on the nuclei of
      cells could be (1) nuclear toxicity/cell death; (2) repair of all the hits and
      then acting as normal cells; or (3) sustaining most of the hits and acting as
      unstable cells. Proliferation of the last type of cell is expected to result in
      transformed cells.

PMID- 9015131
TI  - Ketone potentiation of intrahepatic cholestasis: effect of two aliphatic isomers.
AB  - Occupational exposure to methyl isobutyl ketone (MiBK) or methyl n-butyl ketone
      (MnBK) normally occurs by inhalation. The present study reports that exposure to
      both ketones can potentiate cholestasis experimentally induced by
      taurolithocholic acid (TLC, 30 mumol/kg) or by a combination of manganese (Mn,
      4.5 mg/kg) and bilirubin (BR, 25 mg/kg). Male Sprague-Dawley rats were exposed
      for 3 d, 4 h/d, to MiBK or MnBK vapors using 0.5, 1, 1.5, or 2 times the minimal
      effective concentration (MEC). The estimated MiBK or MnBK MEC for potentiating
      TLC- or Mn-BR-induced cholestasis were 400 and 150 ppm, respectively. Eighteen
      hours after ketone exposure, rats were injected i.v. with TLC or Mn-BR. Bile flow
      was measured from 15 to 150 min after the cholestatic regimen. Rats exposed to
      MiBK or MnBK exhibited an enhanced diminution in bile flow compared to controls
      that was dose-dependent with the inhaled ketone dose. The dose-effect
      characteristics of the potentiation phenomenon were established. Results indicate
      that MiBK or MnBK inhalation potentiated both TLC and Mn-BR cholestasis in a dose
      related fashion. Quantitative differences, however, exist between both ketones
      with respect to their ability to potentiate both models. Comparison between the
      two isomers was established, and MnBK was found to be more potent than MiBK.

PMID- 9015132
TI  - Effects of benzothiophene on male rats following short-term oral exposure.
AB  - The systemic toxicity of benzothiophene, a sulfur-containing heterocyclic present
      in petroleum, coal, and their derived products, was studied in male rats
      following short-term oral exposure. Male Sprague-Dawley rats (130 +/- 20 g) (n =
      5 per dose group) were treated with benzothiophene by gavage at dosages of 0, 2,
      20 or 200 mg/kg/d for 21 d. In another study, male rats were treated with 0, 100,
      or 500 ppm benzothiophene via the diet for 28 d. In the gavage study, the 200
      mg/kg/d rats showed depressed weight gain, increased relative liver and kidney
      weights, decreased relative thymus weights, and elevated levels of serum gamma
      glutamyltransferase (gamma-GT), hepatic aniline hydroxylase (AH), aminopyrine N
      demethylase (APDM), pentoxyresorufin O-dealkylase (PROD), glutathione S
      transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities. A 4.5-fold
      increase in urine volume on d 14-21 and a transient, 4-fold increase in urinary
      ascorbic acid on d 1 were also detected. No treatment related changes in urinary
      N-acetylglucosaminidase (NAGA) activity were observed. Benzothiophene residues
      were not detected in adipose tissue, liver, and serum of rats in the 200 mg/kg
      rats, but a small quantity was detected in the urine. In the diet study, animals
      fed the 500 ppm diet had increased absolute and relative liver weights, elevated
      AH, APDM, and GST activities, decreased red blood cell count, and minor increases
      in serum urea nitrogen and glucose. In summary, benzothiophene produced adverse
      effects in male rats that included increased relative liver and kidney weights
      and increased urine output. Benzothiophene also caused increases in hepatic drug
      metabolizing enzyme activities of a phenobarbital type and a transient elevation
      in urinary ascorbic acid.

PMID- 9015133
TI  - Ingestion of chromium(VI) in drinking water by human volunteers: absorption,
      distribution, and excretion of single and repeated doses.
AB  - This study examines the magnitude of hexavalent chromium [Cr(VI)] absorption,
      distribution, and excretion following oral exposure to 5 and 10 mg Cr(VI)/L in
      drinking water administered as a single bolus dose (0.5 L swallowed in 2 min) or
      for 3 d at a dosage of 1 L/d (3 doses of 0.33 L each day, at 6-h intervals).
      Adult male volunteers ingested deionized water containing various concentrations
      of potassium chromate, and samples of urine, plasma, and red blood cells (RBCs)
      were collected and analyzed for total chromium throughout the studies. In the
      bolus dose studies, a fairly consistent pattern of urinary chromium excretion was
      observed, with an average half life of about 39 h. However, 4-d total urinary
      chromium excretion and peak concentrations in urine and blood varied considerably
      among the 5 volunteers. Studies of repeated exposure to smaller volumes ingested
      at a more gradual rate (i.e., 0.33 L over 5-15 min) showed similar urinary
      chromium excretion patterns but generally lower chromium uptake/excretion. Given
      that sustained elevations in RBC chromium levels provide a specific indication of
      chromium absorption in the hexavalent state, these data suggest that virtually
      all (> 99.7%) of the ingested Cr(VI) at 5 and 10 mg Cr(VI)/L was reduced to
      Cr(III) before entering the blood-stream. The interindividual differences in
      total chromium uptake and excretion are plausibly explained by ingestion of
      appreciable doses on an empty stomach, which likely results in the formation of
      well-absorbed Cr(III) organic complexes in gastrointestinal tissues and possibly
      the blood. The lack of any clinical indications of toxicity in the volunteers and
      the patterns of blood uptake and urinary excretion of chromium are consistent
      with a predominant uptake of Cr(III) organic complexes [derived from Cr(VI)] that
      are excreted more slowly than inorganic forms of Cr(III). Therefore, it appears
      that the endogenous reducing agents within the upper gastrointestinal tract and
      the blood provide sufficient reducing potential to prevent any substantial
      systemic uptake of Cr(VI) following drinking-water exposures at 5-10 mg Cr(VI)/L.
      Based on these data, the chemical environment in the gastrointestinal tract and
      the blood is effective even under relative fasting conditions in reducing Cr(VI)
      to one or more forms of Cr(III).

PMID- 9015134
TI  - The mammalian centromere: its molecular architecture.
AB  - The DNA and protein composition of the centromeric domains in mammalian
      chromosomes is now relatively well characterised. The major families of repeated
      DNAs, i.e., the simple-sequence and alphoids in man and the satellite sequences
      (both minor and major) in the mouse have been sequenced and long-range maps using
      pulse-field gels of some centromeres have been carried out. Autoimmune antibodies
      have provided an insight into some of the proteins which interact with these DNA
      sequences. Although the individual components of the mammalian centromere may
      have been identified, how they interact with each other to give the functional
      structure visualised by electron microscopy is yet to be determined. This review
      examines our understanding of these separate components.

PMID- 9015135
TI  - Immunofluorescent analysis of the organization of telomeric DNA sequences and
      their involvement in chromosomal aberrations in hamster cells.
AB  - We have investigated the organization of telomeric TTAGGG)n repeats in the
      extended DNA loops of chromatin of human and hamster cells by immunofluorescent
      technique. In humans, telomeric repeats which are predominantly localized at the
      termini of all the chromosomes, have been found associated with nuclear matrix.
      This distribution pattern did not alter, even after the removal of 90% of the DNA
      from the nuclear halos by EcoRI digestion. This suggests that the telomeric
      sequences are tightly associated with nuclear matrix and hence cannot be
      solubilized by nucleases. In contrast, in Chinese hamster cells (CHO B11), a
      major proportion of interstitial telomeric repeats are found in the loop regions,
      like beads on a string, with attachments to the periphery of the nuclear matrix.
      Unlike in human cells, EcoRI digestion removed most of the telomeric repeats from
      the loop regions of Chinese hamster cells. This indicates that intrachromosomal
      sequences are not associated with nuclear matrix, and this finding has been
      further substantiated by Southern hybridization of matrix associated and loop DNA
      fractions of hamster cells with the (TTAGGG)n probe. The organizational
      differences in the telomeric repeat sequences of Chinese hamster and human cells
      might be due to their chromosomal location as well as their interaction with
      nucleoprotein complexes specific for the termini of the eukaryotic chromosomes.
      Furthermore, the interstitial (TTAGGG)n sequences were found to be more
      frequently involved in the chromosomal aberrations induced by restriction
      enzymes. This suggests that the intrachromosomal sites of telomeric sequences
      behave as hot spots for DNA damage.

PMID- 9015136
TI  - PRINS localization of centromeres and telomeres in micronuclei indicates that in
      mouse splenocytes chromatid non-disjunction is a major mechanism of aneuploidy.
AB  - Primed In Situ DNA Synthesis (PRINS) of telomeric and centromeric (minor
      satellite DNA) sequences has been applied together with the cytokinesis block
      micronucleus (MN) assay in mouse splenocytes, with the aim of understanding the
      mechanism of origin of spontaneous and induced MN. Splenocyte cultures were
      treated in vitro either with the clastogenic agent mitomycin C or with the
      aneugenic compound colcemid. The relative proportions of MN carrying 1 to 4
      telomeric signals were in agreement with the known mechanism of action of the
      chemicals tested, i.e., an higher number of MN with less than 4 telomeres were
      found in MMC-than in colcemid-treated cultures. No MN lacking the telomeric
      sequences (0 spot) were found, indicating that the observed distributions should
      not be affected by false-negative data. Furthermore, all MN carrying a single
      telomere were negative for the centromere, thus indicating that this class
      represents true chromosome acentric fragments. Finally, MN with 4 telomeric spots
      always carried the centromeric sequence, as expected on the hypothesis that these
      MN correspond to whole chromosomes. With respect to centromere-positive MN, more
      than one half carried 4 telomeric signals (whole chromosomes), and only 1/4 or
      less showed 2 telomeric signals (probably corresponding to a single chromatid).
      This difference was statistically significant, either in untreated cultures or in
      cultures exposed to mitomycin C or colcemid. On the whole, these data indicate
      that non-disjunction followed by whole chromosome loss (with the production of
      two daughter monosomic nuclei) may be the main mechanism of malsegregation
      leading to MN formation.

PMID- 9015138
TI  - Acrocentric chromosome frequency in spontaneous human lymphocyte micronuclei,
      evaluated by dual-colour hybridization, is neither sex- nor age-related.
AB  - The aim of the present paper was to assess the occurrence of acrocentric
      chromosomes in spontaneous micronuclei (MN) of lymphocytes of 20 subjects (10
      males and 10 females) of different ages by means of dual-colour hybridization
      with pancentromeric and acrocentric-specific DNA probes on the binucleate cells
      of each subject. MN were found to contain acrocentric chromosome(s) at an average
      frequency of 26.8%, as compared to a 60% frequency of centromere-positive MN (C +
      MN). As expected, the percentage of total C + MN increased significantly with
      increasing age both of all subjects (r = 0.695, p < 0.001) and women (r = 0.814,
      p < 0.01), while no relationship was found between the frequency of micronuclei
      containing acrocentric chromosome(s) and donor age. This study indicates that the
      frequency of MN containing acrocentric chromosomes is neither over-represented
      nor influenced by age or sex.

PMID- 9015137
TI  - Chemical induction of mitotic checkpoint override in mammalian cells results in
      aneuploidy following a transient tetraploid state.
AB  - Populations of tetraploid cells are found in a variety of human tumours where
      they may act as precursors of aneuploidy and tumorigenesis. Here we demonstrate
      the drug induction of tetraploid cells at mitosis by interference with cell cycle
      checkpoints and the coordination of mitotic events. Tetraploid cells result from
      mitotic exit in the absence of either chromosome segregation or cytokinesis. One
      class of agents that induces tetraploidy causes override of cell cycle
      checkpoints that require metaphase chromosome alignment as a pre-condition for
      initiating exit from mitosis. As a result cells exposed to such drugs progress
      partially through mitosis, but exit without chromosome segregation or
      cytokinesis. Inhibitors of microtubule assembly comprise a second class of agents
      that induce tetraploidy. Many cell types are incapable of maintaining indefinite
      mitotic arrest in the presence of microtubule inhibitors and finally exit mitosis
      without microtubule dependent chromosome segregation. Inhibitors of topoisomerase
      II represent a third class of drugs that induce tetraploidy at mitosis. By
      inhibiting DNA decatenation required for sister chromatid separation at the onset
      of anaphase such drugs block chromosome segregation. When topoisomerase II
      activity is inhibited, cells nonetheless reform nuclei and exit from mitosis
      without chromosome segregation. Finally, inhibition of cleavage furrow formation
      by agents such as cytochalasins represents a fourth mechanism of
      tetraploidization at mitosis. We find that when Chinese Hamster Ovary cells
      become tetraploid, regardless of which mechanism induces this state, they are
      genetically unstable and become aneuploid at the subsequent mitosis. In
      conclusion, the failure of mitotic checkpoint function can generate gross
      aneuploidy from which cells with an advantage for tumor growth may be selected.

PMID- 9015139
TI  - The isolation of rat chromosome probes and their application in cytogenetic
      tests.
AB  - This paper reviews the rat chromosome probes which have so far been isolated in
      our laboratory. The probes can be divided in three groups: a centromere specific
      probe, chromosome-specific point probes and chromosome-specific paint probes. The
      centromere probe 18-5 (member of the rat satellite I family) recognizes the
      centromeres of 16 of the 21 different rat chromosomes and has proved to be very
      useful for the detection of centromeres in micronuclei. Chromosome-specific point
      probes are now available for a least 10 different chromosomes. Four of these
      probes (hybridizing on chromosome 4, 19 (2 different probes) and Y) have proved
      to be very useful for the detection of aneuploidy. Finally, paint probes which
      find their application in the detection of structural chromosome aberrations,
      such as translocations, have been isolated for all rat chromosomes except
      chromosomes 11 and 13-16.

PMID- 9015140
TI  - Analysis of chromosome segregation by means of fluorescence in situ
      hybridization: application to cytokinesis-blocked human lymphocytes.
AB  - The application of methods based on in situ hybridization to centromeric regions
      to cytokinesis-blocked cells provides a convenient way for the analysis of
      chromosome segregation in interphase cells. In this way, the reciprocal
      segregation patterns in daughter nuclei can be visualized and most of the
      problems related to the artefactual loss or gain of chromosomes which flaw other
      methods are avoided. In this work, the methodology has been applied to human
      lymphocytes to investigate the influence of donor age on spontaneous
      malsegregation rates, the occurrence of multiple malsegregation events, and the
      effect of the cytokinesis-blocking agent cytochalasin B (Cyt B) on spontaneous
      and induced chromosome malsegregation. The results obtained with 14 male donors,
      aged 22-57 years, demonstrated a significant (p < 0.001) increase in the
      frequency of micronuclei and X chromosome missegregation (both non-disjunction
      and chromosome loss) with the increasing age of the donors. Moreover, a similar
      association was observed with cultures hybridized with either chromosome 8 or 18
      centromere probes, suggesting that the age-related loss of fidelity in chromosome
      segregation in vitro may be a general trait. The investigation of the
      distribution of multiple malsegregation events in cultured lymphocytes of eight
      male and nine female donors, with the simultaneous hybridization with pairs of
      centromeric probes (for chromosomes X and 8 or X and 18), demonstrated a large
      excess of multiple events with respect to that expected by random segregation.
      This fact may highlight the existence of cellular subpopulation(s) prone to
      malsegregate, or indicate that the malsegregation of one chromosome is able to
      affect the fidelity of segregation of the other chromosomes. Finally, the
      possible influence of Cyt B on chemically induced malsegregation has been
      investigated with the analysis of chromosomes X and 8 signals in nuclei of
      lymphocyte cultures treated with vinblastine (2.5-20 ng/ml) in the presence and
      absence of 6 micrograms/ml Cyt B. Vinblastine induced a small increase in
      hyperploidy of either chromosome X or 8 at 10 ng/ml in cultures treated with Cyt
      B. Without Cyt B, a significant increase of hyperploidy was only observed at the
      highest dose assayed (20 ng/ml). This vinblastine dosage had a severe inhibitory
      effect on cultures treated with Cyt B, where no binucleated cells were detected.
      At all doses, a relatively greater mitotic index was observed in cultures with
      Cyt B, suggesting a synergistic effect of this drug with vinblastine. Most
      notably, at the two highest vinblastine dosages (10 and 20 ng/ml), a large
      incidence of polyploid nuclei was observed in cytokinesis-blocked cultures,
      whereas none or far lower increases of polyploidy were found in the absence or
      Cyt. B. This results provides direct evidence of the potential of Cyt B to
      indirectly interfere with chromosome misdistribution induced by a spindle poison,
      to be considered before drawing firm conclusions from kinesis-blocked systems.

PMID- 9015141
TI  - A study of the aneugenic activity of trichlorfon detected by centromere-specific
      probes in human lymphoblastoid cell lines.
AB  - The potential of the pesticide trichlorfon to induce mitotic aneuploidy has been
      investigated in genetically engineered human lymphoblastoid cell lines.
      Trichlorfon failed to induce micronuclei in the AHH-1 and MCL-5 cell lines when
      treated in media at normal cell culture pH (pH 7.3). Under a treatment pH of 5.5,
      trichlorfon exposures resulted in the induction of both chromosome loss and
      chromosome non-disjunction as measured by fluorescence in situ hybridisation
      (FISH) using a pan-centromeric probe for all human centromeres and centromere
      probes specific for chromosomes 2, 7 and 18. At treatment concentrations greater
      than 20 micrograms/ml trichlorfon also induced structural chromosome damage
      resulting in the production of centromere negative micronuclei.

PMID- 9015142
TI  - Fluorescence in situ hybridisation with chromosome-specific centromeric probes: a
      sensitive method to detect aneuploidy.
AB  - Cytochalasin B-blocked binucleate human lymphocytes from female donors have been
      used to measure micronucleus induction and other aneuploidy events after
      treatment with colchicine, vinblastine or carbendazim. For the aneuploidy events,
      centromeric probes for 6 selected chromosomes (1, 8, X, 11, 17, 18) were used to
      measure chromosome loss, addition and non-disjunction in the interphase nuclei of
      these binucleate cells. The chromosomes were probed in pairs using Cy-3 (red) and
      FITC (green) labels for the 2 different centromeric regions. For colchicine, the
      total non-disjunction frequencies for chromosomes 1 and 8 were similar to the
      total micronucleus frequencies, but were detected as significant at lower
      concentrations. For vinblastine (chromosomes 1 and 8) and carbendazim (all 6
      chromosomes) the frequencies of non-disjunction far exceeded (7 and > 2-fold,
      respectively) the peak frequencies of micronucleus induction. Although most
      chromosomes exhibited similar sensitivity in all the aneuploidy events measured,
      there was an indication that chromosome X was more than susceptible to non
      disjunction than the other chromosomes. We believe that measurement of non
      disjunction in binucleate human lymphocytes using chromosome specific centromeric
      probes offers a sensitive method for detection of aneuploidy and is particularly
      appropriate for the establishment of thresholds.

PMID- 9015143
TI  - Mechanisms of induction of chromosomal aberrations and their detection by
      fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) technique using chromosome specific
      probes has revolutionized the field of radiation cytogenetics in the last few
      years. Some of the new insights on the origins of radiation induced chromosome
      aberrations in human, mouse and Chinese hamster, using FISH are reviewed in this
      paper.

PMID- 9015144
TI  - Spontaneous rates of sex chromosomal aneuploidies in sperm and offspring of mice:
      a validation of the detection of aneuploid sperm by fluorescence in situ
      hybridization.
AB  - This study was designed to evaluate the frequency of aneuploid sperm in young
      adult mice of the genotype (102/E1 x C3H/E1)F1 determined by the fluorescence in
      situ hybridization (FISH) procedure and to evaluate the frequencies of aneuploid
      sperm observed by FISH compared with the frequencies of aneuploid offspring.
      Three-chromosome FISH was applied to determine the fractions of hyperhaploid and
      diploid sperm with DNA probes specific for chromosomes X, Y and 8. The animals
      were treated with three common solvents. Sperm smears were prepared for FISH by
      two similar protocols and were scored by different persons and in two different
      laboratories. There were no significant differences between scorers or
      laboratories. The frequencies of the sex chromosome aneuploidies in sperm (Y-Y
      and X-Y) were compared to the frequencies of mice carrying sex chromosome
      aneuploidy among controls of the heritable translocation assay in studies
      conducted from 1975-1995. To identify aneuploid individuals, untreated males and
      females of the genotype (102/E1 x C3H/E1)F1 were mated to assess their fertility
      by observing three consecutive litters. Semisterile and sterile animals were
      further analysed by meiotic cytogenetics and by karyotyping to determine the
      incidence of reciprocal translocations and sex chromosome aneuploidies (XXY and
      XYY). Based on the analysis of 175247 sperm and 9840 progeny, the frequency of Y
      Y sperm was 0.01% while 0.03% of the offspring were XYY. The frequency of X-Y
      sperm was 0.005% while 0.02% of the offspring were XXY. The frequencies of
      aneuploid sex chromosomes were not significantly different between sperm and
      offspring. This allows two conclusions. First, there was no detectable prenatal
      selection against these sex-chromosomal aneuploid offspring, and second, germ
      cell aneuploidy can be reliably determined in mice by sperm FISH analyses.

PMID- 9015145
TI  - Evidence for a parent-of-origin effect on sperm aneuploidy in mice carrying
      Robertsonian translocations as analyzed by fluorescence in situ hybridization.
AB  - Multi-color fluorescence in situ hybridization (FISH) was employed to investigate
      variations in the frequency of aneuploid spermatids produced by males derived
      from three separate lines of Robertsonian translocations in mice: Rb(2.8)2Lub,
      Rb(8.12)22Lub, and Rb(8.14)16Rma, each with one arm involving chromosome 8. The
      DNA probes used were specific for repetitive sequences on chromosomes 8 and X.
      Heterozygous males for these Robertsonian translocations produced approximately
      1% of spermatids with hyperhaploid for chromosome 8. which was > 80 times higher
      than the frequency of sperm hyperhaploid for chromosome X within the same
      animals; consistent elevations in chromosome-8 sperm disomy were observed among
      lines. In addition, approximately 25% higher fractions of sperm aneuploidy were
      observed when the Robertsonian translocation was inherited from the father rather
      than from the mother (p = 0.009). These findings illustrate the sensitivity of
      the FISH procedure for detecting small differences in the hyperhaploidy in male
      germ cells and suggest that imprinted factors may influence sperm aneuploidy.

PMID- 9015146
TI  - Mechanisms of spontaneous and chemically-induced aneuploidy in mammalian
      oogenesis: basis of sex-specific differences in response to aneugens and the
      necessity for further tests.
AB  - The basis for sex-specific differences in chemically-induced and age-related
      aneuploidy of mammalian germ cells is still unknown. We have analysed the
      maturation of isolated mouse oocytes to characterize the mechanisms underlying
      drug-induced aneuploidy produced by two compounds, chloral hydrate (CH) and
      diazepam (DZ). When administered in vivo both drugs increase hyperploidy in male
      but not in female germ cells. In the assay presented here we show that both CH
      and DZ caused meiotic delay in in vitro maturing mouse oocytes. CH blocked
      meiotic progression irreversibly, affecting even dictyate stage oocytes. DZ
      exposure slowed down maturation but many oocytes may eventually develop to
      metaphase II. Under the influence of CH asymmetric spindles were formed. Often
      chromosomes failed to align properly. This appeared to be responsible for
      triggering a meiotic checkpoint which arrests oocytes in meiosis I. Many oocytes
      escaping the block became 'diploid'. Lagging of chromosomes at anaphase I may
      contribute to significant rises in hypoploidy, while the scattering of
      chromosomes at metaphase II and the premature decondensation of chromatin may
      also predispose oocytes to the formation of structural and numerical chromosomal
      aberrations during meiosis II. In contrast, diazepam appeared to enhance the
      resumption of meiosis in immature oocytes at pharmacologically relevant doses,
      and only at high concentrations lead to a prominent meiotic arrest/delay.
      Importantly, several oocytes matured for 16 h in 25 micrograms/ml DZ displayed
      scattered chromosomes on the spindle and were hyperploid. Concomitantly,
      precocious separation of homologues occurred after DZ, and oocytes contained
      uneven numbers of chromatids, suggesting equational division at anaphase I.
      Cytoplasmic maturation. e.g., association of mitochondria with the spindle was
      disturbed by DZ. We compared the potential of the in vitro test to evaluate the
      aneugenic potential, the targets, threshold concentrations and long-lasting
      effects of relevant environmental pollutants on mammalian oogenesis with the in
      vivo findings, and evaluated the basis for sex-specific responses to aneugens.

PMID- 9015147
TI  - Needle crystals of vitamin B2 induce polyploidy in Chinese hamster lung (CHL/IU)
      cells.
AB  - Induction of polyploidy by vitamin B2 (VB2) was investigated in cultured Chinese
      hamster lung (CHL/IU) cells. We report that VB2 in the form of needle crystals
      induces polyploidy via the formation of CHL/IU cells with more than one nucleus.
      The incidence of polyploid cells depended on the amount of needle crystals. No
      induction of polyploidy was observed when VB2 was used in solution. Electron
      microscopic examination revealed that needle crystals adhered to the cell
      surface, and were enclosed by viscous cellular materials. These results indicate
      that needle crystals of VB2 have the ability to induce polyploidy in cultured
      CHL/IU cells, probably by physically fixing the shape of the cells and by this
      preventing normal mitosis.

PMID- 9015148
TI  - Dose-response of X-irradiated human and equine lymphocytes.
AB  - We have investigated and compared DNA damage and cell killing induced in human
      and equine lymphocytes after in vitro X-irradiation. Our data show that the
      cytogenetic and the lethality effects are both greater in equine lymphocytes, but
      that the difference is wider for lethality. The ratios between doses inducing the
      same effect are 1.3, 1.7 and 9.4 for the number of binucleated cells with
      micronuclei, micronucleus frequency in binucleated cells and DNA synthesis
      inhibition, respectively. The very different radiosensitivity observed for the
      two mammalian species encourages us to use their lymphocytes in cell radiobiology
      studies.

PMID- 9015149
TI  - Targeted base substitutions and small deletions induced by neocarzinostatin at
      the APRT locus in plateau-phase CHO cells.
AB  - Treatment of confluence-arrested CHO-D422 cells for 48 h with low concentrations
      (0.5-3 nM) of the radiomimetic antibiotic neocarzinostatin resulted in an
      increase in up to 11-fold in the frequency of mutations at the hemizygous APRT
      locus. Analysis by PCR and DNA sequencing revealed that the mutations were a
      mixture of base substitutions, small deletions, and large-scale rearrangements.
      base substitutions occurred preferentially at sequence positions where the drug
      is known to produce abasic sites with closely opposed strand breaks, e.g., AGT,
      TGT and AGC, where the abasic site occurs at the underlined base and the strand
      break occurs opposite the first base in each triplet. These results suggest that
      the substitutions were produced by replicative bypass of the abasic sites,
      perhaps during attempted repair of the accompanying strand break. Single-base
      deletions, which comprised nearly half of all deletions, were targeted to these
      same sequence positions, suggesting that they may have been generated either by
      replicative bypass of the abasic sites, or by end-joining repair of double-strand
      breaks, which are induced the same sites. Quantitative analysis of
      neocarzinostatin-induced damage to APRT DNA in vitro confirmed the association
      between lesions involving concommitant damage to both DNA strands, and mutations.
      The results are consistent the hypothesis that agents which induce such
      bistranded DNA damage can produce biologically significant levels of mutagenesis
      even in nondividing cells.

PMID- 9015150
TI  - Repair of gamma-irradiation-induced DNA single-strand breaks in human bone marrow
      cells: effects of a second irradiation.
AB  - Human bone marrow mononuclear cells were isolated by density gradient
      centrifugation and irradiated with a 137Cs source. The extent of irradiation
      induced single-strand breaks (SSBs) and alkali labile sites as well as their
      repair was investigated by using the alkaline single-cell gel electrophoresis
      (SCGE) technique, or comet assay. A dose-dependent increase in the length of DNA
      migration was seen when cells were exposed to 0, 2.43 and 5.43 Gy of gamma
      irradiation. Complete repair of DNA SSBs was observed over 24 h after a dose of
      2.43 Gy. Second challenges of 0, 2.43 and 5.43 Gy resulted in similar SSBs as
      with the first irradiation. Furthermore, the DNA repair kinetics of two cell
      populations, one previously unirradiated and the other having received 2.43 Gy 24
      h earlier, was indistinguishable. This means that most human bone marrow cells
      retain their genetic stability after a dose of 2.43 Gy if SSBs are used as an
      endpoint.

PMID- 9015151
TI  - Micronuclei induction by 131I exposure: study in hyperthyroidism patients.
AB  - To evaluate the eventual genetic damage induced by therapeutic exposure to 131I,
      we have studied the presence of micronuclei (MN) in binucleated peripheral blood
      lymphocytes from a group of 28 hyperthyroidism patients who received 131I sodium
      iodide, via oral administration. The study was conducted over time and blood
      samples were obtained before the treatment, and 1 week, 1 month and 3 months
      after it. The results obtained indicate a positive relationship between dose and
      BNMN frequency as calculated by the linear regression coefficient, showing
      significant increases in the frequency of MN and BNMN (binucleated cells with MN)
      in the subgroup of patients that received more than 500 MBq. Taking into account
      that the patients studied were treated with relatively low doses of 131I, our
      positive results support the view that the MN assay is sensitive enough to
      monitor the chromosome damage resulting from the exposure.

PMID- 9015152
TI  - Clastogenic factors in the plasma of children exposed at Chernobyl.
AB  - Clastogenic factors (CFs), as they were described previously in accidentally or
      therapeutically irradiated persons, in A-bomb survivors and in liquidators of the
      Chernobyl nuclear power plant, were also detected in the plasma of Chernobyl
      exposed children. A high percentage of plasma ultrafiltrates from 170 children,
      immigrated to Israel in 1990, exerted clastogenic effects in test cultures set up
      with blood from healthy donors. The differences were highly significant in
      comparison to children immigrated from 'clean' cities of the former Soviet Union
      or children born in Israel. The percentage of CF-positive children and the mean
      values of the adjusted clastogenic scores (ACS) were higher for those coming from
      Gomel and Mozyr, which are high exposure sites (IAEA measurements), compared to
      those coming from Kiev. There was no correlation between residual 137-Caesium
      body burden and presence of CFs. However, both measurements were not done at the
      same time (in 1990 and 1992-1994, respectively). Also no relationship could be
      revealed between enlargement of the thyroid gland and CF-positivity. CFs are not
      only observed after irradiation, but in a variety of chronic inflammatory
      diseases with autoimmune reactions. They were also described in the congenital
      breakage syndromes, which are hereditary diseases with the highest cancer
      incidence in humans. Whether the clastogenic effects continuously produced by
      circulating CFs represent a risk factor for malignant late effects deserves
      further study and follow-up. Since CF formation and CF action are mediated by
      superoxide radicals, prophylactic treatment with antioxidants may be suggested
      for Chernobyl-exposed children, whose plasma induces a strongly positive CF-test.

PMID- 9015153
TI  - Increase in the mitotic recombination frequency in Drosophila melanogaster by
      magnetic field exposure and its suppression by vitamin E supplement.
AB  - In order to estimate possible mutagenic and/or carcinogenic activity of
      electromagnetic fields, wing spot tests were performed in Drosophila
      melanogaster. A DNA repair defective mutation mei-41D5 was introduced into the
      conventional mwh/flr test system to enhance mutant spot frequency. Third instar
      larvae were exposed to a 5-Tesla static magnetic field for 24 h, and after
      molting, wings were examined under a microscope to detect hair spots with mutant
      morphology. The exposure caused a statistically significant enhancement of
      somatic recombination compared with the unexposed control. This enhancement was
      suppressed to the control level by supplement of vitamin E, a non-specific
      antioxidant. It is inferred that the magnetic field enhanced the genotoxic effect
      of spontaneously produced free radicals, possibly by affecting the lifetime of
      the radicals. Enhancement of non-disjunction, terminal deletions and gene
      mutations were not detected.

PMID- 9015154
TI  - Enhanced generation of A:T-->T:A transversions in a recA730 lexA51(Def) mutant of
      Escherichia coli.
AB  - RecA730 belongs to a class of mutant RecA protein that is often referred to as
      RecA*, since it is constitutively activated for coprotease functions in the
      absence of exogenous DNA-damage. Escherichia coli strains carrying recA730 (or
      other recA* alleles) exhibit dramatic increases in SOS-dependent spontaneous
      mutator activity. We have analyzed the specificity of this mutator phenotype by
      employing F'-plasmids carrying a set of mutant lacZ genes that can individually
      detect two types of transitions, four types of transversions, and four kinds of
      specific frameshift events. Analysis revealed that most of the spontaneous
      mutagenesis in a recA730 lexA51(Def) strain (which expresses derepressed levels
      of all LexA-regulated proteins) can be attributed to a specific increase in A:T-
      >T:A, A:T-->C:G and G:C-->T:A transversions, with the A:T-->T:A transversions
      occurring most frequently. These transversion events were completely abolished in
      a delta umuDC strain, indicating that the functionally active UmuD'C proteins are
      normally required for their generation. The spectrum obtained was similar to that
      of strains with a defect in the epsilon (3'-->5' proofreading) subunit of DNA
      polymerase III. Such an observation raises the possibility that the wild-type
      epsilon protein is in activated in strains expressing the RecA730 and UmuD'C
      proteins.

PMID- 9015155
TI  - Production of unscheduled DNA synthesis in rodent hepatocytes in vitro, but not
      in vivo, by 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX).
AB  - Incubation of both rat and mouse hepatocytes with 3-chloro-4-(dichloromethyl)-5
      hydroxy-2[5H]-furanone (MX) in vitro resulted in a dose-dependent increase in
      unscheduled DNA synthesis (UDS) at sub-cytotoxic concentrations (1-10 microM MX;
      20 h incubation). Depletion of glutathione stores by pre-treatment of rat
      hepatocytes with buthionine sulfoximine did not result in a significant increase
      in UDS produced by MX. In contrast, MX did not induce UDS in mouse hepatocytes ex
      vivo either 3 or 16 h following administration of a single oral dose of 100 mg/kg
      MX. Despite the ability of MX to produce repairable DNA damage, restricted access
      of MX to the liver may prevent a measurable UDS response in vivo.

PMID- 9015156
TI  - Chinese hamster cells expressing antisense to metallothionein become spontaneous
      mutators.
AB  - The functions of metallothioneins (MTs) have been debated for at least a decade.
      Because it seems unlikely that they evolved only to protect cells against
      exogenous heavy metals, it has been suggested that MTs have roles in scavenging
      reactive intermediates, controlling zinc and copper homeostasis, and controlling
      transfer of zinc to transcription factors and other proteins. Previously, we
      demonstrated that Chinese hamster G12 cells which overexpress MT have greatly
      reduced spontaneous mutation rates, suggesting that MT evolved to prevent
      spontaneous mutagenesis induced by free nuclear zinc ions. We have now isolated
      G12 transfectants which express antisense RNA to MT. Immunofluorescent staining
      reveals MT protein in both the nucleus and the cytoplasm in parental cells. A
      clone expressing high levels of antisense RNA (AMT30) shows reduced basal and
      induced levels of MT protein. AMT30 cells are hypersensitive to cadmium, zinc,
      copper and mercury chlorides as well as to menadione. Glutathione levels in AMT30
      and G12 cells do not differ. AMT30 cells are spontaneous mutators, showing a
      spontaneous mutation rate 5-10 times that of G12 cells or G12 cells transfected
      with vector alone. Only transfectants which show a high level of MT antisense
      expression (i.e., AMT30) had greatly elevated spontaneous mutation rates. These
      results support our hypothesis that a major role of MT is to act as an endogenous
      antimutagen probably via scavenging of reactive intermediates in the nucleus.
      AMT30 cells should be useful in delineating the sources of spontaneous
      mutagenesis.

PMID- 9015157
TI  - The tumor suppressor p53 modifies mutational processes in a human lymphoblastoid
      cell line.
AB  - Abnormalities in the p53 gene play an important role in genomic instability and
      tumorigenesis. Our previous work showed that p53 status is correlated with
      differential mutability in two closely related human lymphoblastoid cell lines,
      TK6 and WTK1. WTK1 cells, which contain a mutation in p53 (p53Ile237) show a
      remarkably increased mutability, larger genetic alterations at the thymidine
      kinase locus (tk), an increased ability to catalyze recombination, and a delay in
      the onset of apoptosis after X-irradiation, compared to TK6 (p53 +/+). In the
      present study, we demonstrate that after transfection and subsequent
      overexpression of the known dominant negative mutant p53 Ala143 allele
      (mp53Ala143) in TK6, there were significantly enhanced spontaneous and X-ray
      induced mutant frequencies at the tk locus, and delayed onset of X-ray-induced
      apoptosis, to a similar extent as in WTK1. In addition, high protein expression
      of mp53Ala143 in transfectants was correlated with both increased mutation
      frequency and altered apoptosis kinetics. Similar results were obtained with p53
      Ile237 transfection into TK6. Our observations indicate that the product of the
      p53 gene affects mutational processes. We hypothesize that p53 dysfunction can
      lead to increased mutagenicity at the endogenous tk gene in human lymphoblastoid
      cell lines either through delayed apoptosis in response to DNA damage or by
      mediating increased recombination.

PMID- 9015158
TI  - Detection of mutagenicity in Ames test using a metalloporphyrin/oxidant model
      system for cytochrome P450.
AB  - A chemical model system for cytochrome P450, a porphyrin and an oxidant, was used
      in Ames assay as a substitute for S9 mix. In the presence of
      tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride [Fe(F5P)Cl] and tert
      butyl hydroperoxide (t-BuOOH), mutagenicity of N-nitrosodibutylamine (NDB) in
      Salmonella typhimurium TA1535 was detected. The mutagenicity depended on the pre
      incubation period, and also on the concentration of an oxidant and of bacteria.
      In the chemical model system, pH affected the mutagenicity of NDB, which
      suggested that as observed in an enzymatic activating system, the mutagenicity
      was due to the labile alkylating species which was derived from NDB activated in
      the chemical activation system and was sensitive to pH. Under the optimum
      conditions; a higher concentration of an oxidant, a higher concentration of
      bacterial culture, and a weakly acidic medium, mutagenicity of N
      nitrosodipropylamine in S. typhimurium TA1535 was also detected. Besides N
      nitrosodialkylamines, 2-aminofluorene (2-AF) and benzo[a]pyrene (BaP) were also
      used as mutagens. Mutagenicity of 2-AF and BaP in S. typhimurium TA1538 were both
      detected in the same system as used in detecting the mutagenicity of N
      nitrosodialkylamines. Ames test using a metalloporphyrin/oxidant model system
      makes it possible to detect mutagenicity derived from both base pair substitution
      mutagens and frameshift mutagens without using enzymatic activating system. These
      results demonstrate that the assay with the chemical model system is useful in
      detecting unstable unknown active mutagens or investigating the mechanisms of the
      metabolic pathway of mutagens or carcinogens in a protein-free medium.

PMID- 9015159
TI  - Heavy cigarette smokers show higher mutagenicity in urine.
AB  - We examined the mutagenicity of cigarette smoker's urine in 32 healthy male
      cigarette smoker and 37 healthy male non-smoker. Twenty-four-hour urine specimens
      were subjected to blue rayon extraction which selectively adsorb polycyclic
      compounds, after which the elutions were fractionated by carboxymethyl cellulose
      column chromatography for removing antimutagenic compounds. The mutagens were
      measured by using an S9-mediated Salmonella mutagenicity test on strain TA98.
      Compared with those with non-smokers, smokers' urine showed a significantly
      higher urinary level of mutagens in the acid-elutable and in the sum of all
      chromatography fractions. A similar tendency was also seen in the alkali-elutable
      fraction. The subjects were classified into three groups according to the number
      of smoked cigarettes. Heavy smokers, who smoked more than 20 cigarettes per day,
      showed a significantly higher urinary level of mutagens than both non-smokers and
      light smokers especially in the acid-elutable and in the sum of all
      chromatography fractions. Our findings suggest that smokers are exposed to a
      great amount of polycyclic carcinogens and mutagens by cigarette smoking. These
      results also suggest that urinary level of mutagens measured by using blue rayon
      extraction combined with carboxymethyl cellulose chromatography could be a good
      index for estimating the exposure to carcinogens and mutagens such as polycyclic
      compounds.

PMID- 9015160
TI  - Benzene-, catechol-, hydroquinone- and phenol-induced cell transformation, gene
      mutations, chromosome aberrations, aneuploidy, sister chromatid exchanges and
      unscheduled DNA synthesis in Syrian hamster embryo cells.
AB  - Benzene is a human carcinogen present naturally in petroleum and gasoline. For
      the simultaneous assessment of benzene-induced carcinogenicity and mutagenicity,
      benzene and its principal metabolites, phenol, catechol and hydroquinone were
      examined for their ability to induce cell transformation and genotoxic effects
      using the same mammalian cells in culture. Each of the four compounds induced
      morphological transformation of Syrian hamster embryo (SHE) cells. Catechol was
      the most potent, inducing transformation at concentrations of 1-30 microM,
      followed by hydroquinone (3-30 microM), phenol (10-100 microM) and benzene (only
      at 100 microM). Gene mutations at two loci in SHE cells were induced by all four
      compounds, with catechol being the most potent; both ouabain-resistant and 6
      thioguanine-resistant mutant frequencies were increased. Chromosomal aberrations
      in SHE cells were especially induced by catechol, lesser by hydroquinone, and to
      a marginal extent by phenol at only the 100 microM concentration, whereas sister
      chromatid exchanges in SHE cells occurred with hydroquinone (1-30 microM),
      catechol (10-30 microM) and phenol (1000-3000 microM). Aneuploidy in the near
      diploid range of SHE cells was significantly induced by benzene and catechol. All
      three metabolites induced unscheduled DNA synthesis in SHE cells, whereas benzene
      did not. This is the first report that the cell transforming activity and
      mutagenicity of benzene and its metabolites were assessed with the same mammalian
      cells in culture. The results provide evidence that benzene and several of its
      metabolites are cell transforming and genotoxic to cultured mammalian cells.

PMID- 9015161
TI  - Molecular spectrum of mutations induced by 5-hydroxymethyl-2'-deoxyuridine in
      (CHO)-PL61 cells.
AB  - We have utilized (CHO)-PL61 cells to characterize the mutations produced in
      mammalian cells by exogenous treatment with the nucleoside 5-hydroxymethyl-2'
      deoxyuridine (hmdUrd). HmdUrd is incorporated into DNA as a thymidine analogue
      and is removed by the repair enzyme hmUra-DNA glycosylase. PL61 cells are hprt(-)
      and contain adjacent single copies of the Escherichia coli gpt and neo genes
      (gpt+, neo+) separated by 2 kb, rendering the cells thioguanine sensitive (TGs)
      and geneticin resistant (G418r). Cells were exposed to hmdUrd and the colonies
      resistant to thioguanine or thioguanine and G418 were selected. Selection in
      thioguanine alone (TGr/gpt(-)) allows the growth of all gpt(-) mutants (small,
      intermediate and large deletions/insertions and point mutations) while selection
      in thioguanine and G418 (TGr/gpt(-), G418r/neo+) prevents survival of colonies
      containing vary large deletions of the gpt gene that include the neo gene. To
      confirm the types of mutation at the molecular level, the gpt gene was amplified
      from mutants' genomic DNA by PCR, and the amplified DNA was sequenced directly by
      the dideoxy method. Our study showed that 4 microM hmdUrd induced mutations to
      TGr/gpt(-) at a rate 3-4 times that of control, but showed no marked increase in
      mutation to TGr/gpt(-), G418r/neo+. The predominant type of hmdUrd induced
      mutation in the thioguanine resistant cells at the gpt locus was complete loss of
      the gpt gene resulting from a large deletion. Background mutations were generally
      point mutations or small insertion/deletion mutations. We propose that hmdUrd
      induces large/intermediate deletions as a major type of mutations in mammalian
      cells as a consequence of DNA repair, and not as a result of misincorporation or
      mispairing, suggesting that base excision repair by itself can lead to large
      deletion mutagenesis.

PMID- 9015163
TI  - Sensory systems.

PMID- 9015162
TI  - M-phase specific centrosome-microtubule alterations induced by the fungicide MBC
      in human granulosa cells.
AB  - The mitostatic action of the commonly used fungicide methyl 2
      benzimidazolecarbamate (MBC) was evaluated in primary cultures of human ovarian
      granulosa cells with respect to the organization and stability of spindle
      microtubules and mitotic centrosomes. MBC caused metaphase arrest and abnormal
      chromosome organization following a 3-15 h treatment at a concentration of 30
      microM. While microtubules were retained in MBC-treated cells, alterations in
      spindle shape and microtubule composition were noted. Exposure to MBC resulted in
      an increased number of spindle poles associated with chromosomes displaced from
      the metaphase plate. A gradual increase from tri- to multipolar spindles was
      noted with prolonged treatment although a relatively constant fraction (50%) of
      bipolar spindles was maintained. In non-dividing cells, MBC had no effect on
      microtubule organization. Analysis of mitotic figures by immunofluorescence
      microscopy showed a reduction in interpolar and astral microtubules in response
      to MBC treatment while acetylated kinetochore microtubules were retained and
      their plus-ends were attached to metaphase chromosomes. In multipolar spindles,
      analysis of microtubule organizing centers (MTOCs) with antisera to stable
      centrosomal markers (SPJ and 5051) revealed that only poles associated with
      displaced chromosomes retained these markers. In contrast, transient centrosome
      markers (NuMA and centrophilin) were localized to all poles of multipolar
      spindles. Since MBC alters centrosome organization during mitosis, the results
      suggest that one mechanism of action of this agent is impairment of spindle
      microtubule dynamics at the centrosome.

PMID- 9015164
TI  - Accuracy of current educational literature on the staging of gastric carcinoma.
AB  - Staging of gastric adenocarcinoma is important for comparing aspects of the
      disease in Asia and in the Western countries, and it may be used to direct the
      treatment strategy. A survey of 13 popular current surgical textbooks and review
      journals found a high level of inaccuracy. Two texts (15%) did not mention any
      staging systems, and one (8%) described a nonstandard system. Three (23%)
      described staging systems that were out of date, and six descriptions (46%) were
      inaccurate. Only 40% of the cited staging systems was reliable. This level of
      inaccuracy leads to confusion for the reader and to difficulty interpreting other
      relevant literature.

PMID- 9015165
TI  - Relations among plasma prolactin, testosterone, and injury severity in war
      casualties.
AB  - Tissue trauma leads to a complex hormonal response of pituitary end-organ axis.
      This response can be recorded by determining parameters that represent the
      functional integrity of these systems. The concentrations of serum prolactin
      (PRL), serum testosterone, and plasma adrenocorticotropin (ACTH) were measured in
      62 adult male casualties from the recent war in former Yugoslavia. Patients with
      brain injury were not included. Venous blood samples were taken as soon as
      possible (2-18 hours) after admission and at 1, 2, 5, and 14 days after injury.
      The severity of gunshot/missile wounds was assessed by the Injury Severity Score
      (ISS). The control group consisted of healthy blood donors. Uninjured subjects
      who had undergone great stress on the battlefield (explosion in the vicinity
      without injury) served as the sham-control group. Tissue trauma leads to a
      severity-dependent decrease in serum testosterone concentrations during the first
      5 days following injury. Significant correlations were observed between ACTH,
      prolactin, and ISS during the first 18 hours after injury. A strong negative
      correlation between testosterone and prolactin serum concentrations was found
      during the first 18 hours. In patients with additional complications or
      unsatisfactory outcome, the prolactin concentrations remained elevated, whereas
      testosterone concentrations were reduced. Our results support the usefulness of
      recording hormonal changes for determining trauma severity and monitoring the
      clinical course. Such monitoring also helps assess the efficacy of therapeutic
      strategies. The relation between testosterone and prolactin might be helpful for
      predicting the clinical course and trauma outcome.

PMID- 9015166
TI  - Complications and nonclosure rates of fasciotomy for trauma and related risk
      factors.
AB  - The objective of this study was to identify risk factors for the development of
      complications and unsatisfactory skin closure following fasciotomy for trauma.
      Risk factors included in the study are prolonged time from injury to fasciotomy,
      type of fasciotomy, site of injury, and kind of underlying injury. The study was
      a retrospective analysis of 100 consecutive fasciotomies done for trauma over a
      period of 38 months (December 1991 to January 1995) in a "level I" trauma center
      at a university-affiliated county teaching hospital. Ninety-four patients were
      eligible for analysis, 29 of whom (31%) developed complications at the fasciotomy
      site. The risk was increased for lower extremity versus upper extremity (34.3%
      versus 20.8%), prophylactic versus therapeutic (42.0% versus 24.6%), late (>8
      hours) versus early (37% versus 25%), and vascular versus musculoskeletal (38.8%
      versus 22.2%) trauma cases. The same risk factors negatively influenced the
      ability to close the skin primarily. The four subgroups defined by
      vascular/nonvascular injury and upper/lower extremity site had significantly
      different nonclosure rates (p = 0.043). The rate was highest among the
      vascular/lower extremity group (60.5%) and lowest among the nonvascular/upper
      extremity group (15.4%). We concluded that fasciotomies in lower extremities, the
      presence of underlying vascular injuries, fasciotomies performed
      prophylactically, and a time between the injury and fasciotomy of more than 8
      hours are associated with an increased risk for local complications. The same
      factors are associated with an increased need for skin grafting the wound.

PMID- 9015167
TI  - Jet-cutting supported by high frequency current: new technique for hepatic
      surgery.
AB  - To reduce blood loss incurred during liver resection, techniques that separate
      vessels from liver parenchyma, such as the CUSA or the jet-cutter, are in
      clinical use. By conducting high frequency current through the jet beam using
      hypertonic NaCl cutting solution, we developed a new method enabling simultaneous
      coagulation during selective cutting. In this study we examined the effects of
      this method on liver resection in a rabbit model. With the three techniques-jet
      cutting, CUSA, and high frequency-supported jet-cutting (HF-jet)-we performed
      liver resection of the ventral lobe in six animals per group. We compared
      velocity of resection, blood loss, tissue trauma, selectivity (number of isolated
      vessels per area), electrolytes, and vital signs. Histopathology was carried out
      with the resectate and after 7 days with the remaining liver. Velocity of
      resection procedure and selectivity were significantly reduced in the HF-jet
      group. Histopathology showed coagulated vessels and a deeper zone of necrosis.
      Accordingly, the liver enzymes transiently showed distinctly higher values in the
      HF-jet group. Electrolyte disturbances or differences of vital signs could not be
      detected. Transferring our results to patient care we expect that with major
      resections the hilus clamping time, blood loss, and number of blood transfusions
      can be reduced. In our opinion the additional application of high frequency
      through the jet beam is a helpful improvement of the jet-cutter.

PMID- 9015168
TI  - Laparoscopic highly selective vagotomy: technical considerations and preliminary
      results in 119 patients with duodenal ulcer or gastroesophageal reflux disease.
AB  - The technical considerations and preliminary results of 119 patients submitted to
      laparoscopic highly selective vagotomy are presented. There were 33 with duodenal
      ulcers, 31 with duodenal ulcers plus gastroesophageal reflux, and 55 with
      gastroesophageal reflux. Operating time varied from 120 to 160 minutes. Six
      complications occurred: four perforations of the gastric fundus and two bleeding
      episodes. Conversion to open surgery was done in four cases and reoperation in
      one case. No deaths occurred, and the mean hospital stay was 3 days. The mean
      follow-up was 16 months, being 94% of the cases with Visick I or II and 6% with
      Visick III or IV. This technique is completely feasible by laparoscopic procedure
      and reproduces exactly what has been done with the laparotomy approach.

PMID- 9015169
TI  - Ultrasound-guided aspiration biopsy for detection of nonpalpable axillary node
      metastases in breast cancer patients: new diagnostic method.
AB  - This study was designed to evaluate the accuracy of ultrasonography alone and in
      combination with fine-needle aspiration biopsy (FNAB) for detection of axillary
      metastases of nonpalpable lymph nodes in breast cancer patients. Ultrasonography
      was carried out in 150 axillas of 148 patients (mean age 57 years, range 30-80
      years); and in 93 axillas lymph nodes were detected. Nodes were described
      according to their dimension and echo patterns and were compared with
      histopathologic results. FNAB was carried out in 81 axillas (122 nodes). The
      sensitivity of ultrasonography was highest (87%) when size (length >5 mm) was
      used as criterion for malignancy, but the specificity was rather low (56%). When
      nodes with a malignant pattern (echo-poor or inhomogeneous) were visualized,
      specificity was 95%. Ultrasound-guided FNAB had a sensitivity of 80% and a
      specificity of 100% and detected metastases in 63% of node-positive patients. It
      is concluded that FNAB is an easy, reliable, inexpensive method for identifying
      patients with positive nodes. In the case of negative findings, other diagnostic
      procedures to exclude lymph node metastases, such as sentinel node mapping, could
      be performed.

PMID- 9015170
TI  - Pattern of recurrence after extended radical esophagectomy with three-field lymph
      node dissection for squamous cell carcinoma in the thoracic esophagus.
AB  - Factors responsible for recurrence of esophageal cancer were investigated in 90
      patients who underwent extended radical esophagectomy with three-field dissection
      for a squamous cell carcinoma in the thoracic esophagus. The initial tumor
      recurrence was grouped as either locoregional (site of the primary tumor,
      anastomotic site, or lymph nodes) or as distant (distant organs, pleura, or
      peritoneum). Nineteen patients (21%) developed a locoregional recurrence, and 19
      (21%) developed a distant recurrence. One (1%) developed both recurrences
      simultaneously and was classified as a distant recurrence. The locoregional
      recurrence was correlated with the stage factors, particularly the number of
      metastasis-positive nodes. For the distant recurrence, vascular invasion was
      found to have been the most important prognostic factor. Our findings suggested
      that locoregional recurrence was due to tumor progress related to the extent of
      lymph node metastasis, whereas distant recurrence was due to the oncologic
      behavior of the tumor. Locoregional recurrence in patients with limited disease
      may be reduced by extended radical esophagectomy with three-field dissection.
      Distant recurrence cannot be controlled by surgery. Adopted postoperative
      adjuvant therapies showed no effect on recurrence.

PMID- 9015171
TI  - Appraisal of ten-year survival following esophagectomy for carcinoma of the
      esophagus with emphasis on quality of life.
AB  - Characteristics of 10-year survival after esophagectomy for carcinoma were
      studied retrospectively in 161 patients who underwent curative operation between
      1973 and 1984. Of the 161 patients, 44 (27.3%) survived for 10 years after
      operation (right transthoracic approach with cervical anastomosis in 36 patients
      and left thoracoabdominal approach with jejunoesophagostomy in 8 patients).
      Females survived significantly longer than males; 10-year survival was observed
      in 10 (50%) of 20 females and 34 (24.1%) of 141 males. TNM factors were
      significantly linked to the 10-year survival for 25 patients (56.8%) whose tumors
      invaded the adventitia and 20 patients (45.5%) who had lymph node metastases,
      where the total number of involved nodes was less than eight. A questionnaire
      mailed 10 years after operation revealed that about one-fifth of the 10-year
      survivors could not go up one flight of stairs without taking a rest, and that
      the daily activity significantly deteriorated if the patient's age at the time of
      surgery was more than 66 years. One-third of the 10-year survivors were not
      satisfied with the daily quantity of food intake, resulting in no gain of body
      weight after discharge from the hospital. This complaint was significantly
      correlated with either weekly reflux or heartburn, resulting in the increasing
      number of nonmalignancy deaths. Of 13 ten-year survivors who were alive at 10
      years but died after that, 11 (84.6%) died of pneumonia or malnutrition.
      Duodenogastroesophageal reflux may eventually cause nonmalignancy death 10 years
      after esophagectomy for carcinoma.

PMID- 9015172
TI  - High-resolution ultrasonography: highly sensitive, specific technique for
      preoperative localization of parathyroid adenoma in the absence of multinodular
      thyroid disease.
AB  - The objective of this prospective study was to evaluate the role of preoperative
      ultrasonography (US) for parathyroid lesion localization in patients with primary
      hyperparathyroidism (PHPT) prior to initial surgery. Fifty-two consecutive
      patients with PHPT, diagnosed in our institution within a period of 2 years, were
      referred for preoperative US and subsequently for bilateral surgical neck
      exploration. The combination of a confirmatory pathologic report and
      normalization of blood calcium concentration for a period of at least 3 months
      was considered an operative success. In 50 patients (96.2%) a single parathyroid
      adenoma was excised, and in one patient (1.9%) hyperplasia of three glands was
      found at surgery. In the one surgical failure, no parathyroid pathology was
      identified in the neck; therefore the operative success in this series was 98%.
      The sensitivity of preoperative US was 83% with a specificity of 100%. In the
      absence of thyroid multinodular disease (MND), the sensitivity of preoperative US
      increased to 90%, whereas in patients with MND the sensitivity was only 64%. Our
      findings support the notion that patients with PHPT should be investigated with
      US before initial surgery. Bilateral surgical exploration is warranted in
      patients with MND. In the absence of such thyroid pathology, an US finding
      positive for adenoma should allow the surgeon to perform unilateral neck
      exploration only, with consequent reduction of operation time and postoperative
      complications.

PMID- 9015173
TI  - Repeat hepatic resection for recurrent colorectal cancer.
AB  - Recurrence in the liver following hepatic resection for metastatic colorectal
      carcinoma is a predictable phenomenon, occurring in about two-thirds of patients
      who develop recurrence. There are few data, however, about the value of repeated
      hepatic resection in patients who have a recurrence in the liver following
      initial resection of their hepatic metastases. We have reviewed our experience
      with 10 patients (of whom 9 were evaluable), culled from a series of 74 patients
      who had an initial hepatic resection for metastatic colorectal carcinoma. There
      were seven men and two women, mean age 52 (range 34-75 years). Duke's stages of
      the primary cancer were B1 in two patients, B2 in one patient, and C2 in six
      patients. Most of the patients had elevated carcinoembryonic antigen (CEA) and
      constitutional symptoms as indications for the second-look procedure. There was
      one surgical death due to hepatic failure in a patient who required a
      trisegmentectomy. The average interval between the first and second hepatic
      resections was 21 months. The estimated 1- and 5-year actuarial survivals from
      the second liver resection were 78% and 23%, respectively. The median survival
      was 41 months from the first resection (range 14-100 months) and 16 months from
      the second resection (range 0-92 months). In conclusion, repeat hepatectomy for
      recurrent liver metastases is a viable option for the well selected patient. It
      is a low risk surgical procedure and may augment survival in the patient with
      well documented metastases limited to the liver.

PMID- 9015174
TI  - Anatomic dissociation between the intrahepatic bile duct and portal vein: risk
      factors for left hepatectomy.
AB  - The anatomic variations of the intrahepatic portal vein and bile duct were
      analyzed to evaluate the potential risk of left hepatectomy. A total of 210
      cholangiograms and hepatic arterioportograms were performed in which the
      ramifications of the intrahepatic portal vein and bile duct were investigated.
      The orientation of the intrahepatic duct and portal vein were classified into
      five types. In 175 patients (83.33%), the intrahepatic portal vein and bile duct
      had the same anatomic classification. In 24 patients (11.43%), the right anterior
      or posterior intrahepatic duct drained into the left hepatic duct at the
      umbilical portion (type IV); there were only 15 patients (7.14%) whose portal
      veins fell into this category. All patients with type IV portal veins had type IV
      hepatic ducts, but there were 9/49 patients (18.36%) whose hepatic duct
      distribution belonged to type IV but their portal veins belonged to type II (6
      cases) or III (3 cases). Without complete knowledge of the intrahepatic portal
      and biliary anatomy, insufficient portal perfusion and bile duct complications
      may result from the left hepatectomy operation. Preoperative portal vein
      evaluation or left portal vein clamping can provide significant information, but
      there are still 18.36% of patients where type IV biliary ducts were not detected
      in those with type II and III portal veins. Cholangiography is of paramount
      importance in these two groups of patients, as it can prevent inadvertent injury
      to the right intrahepatic ducts, which drain into the left intrahepatic duct. On
      the other hand, intraoperative ultrasonography is recommended to identify or
      exclude an aberrant portal vein if type VI biliary anatomy is detected during
      intraoperative cholangiography.

PMID- 9015175
TI  - Intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma is an uncommon neoplasm of liver compared with
      hepatocellular carcinoma. Hepatic resection seems to provide the only chance for
      therapeutic success. The records of 77 patients with intrahepatic
      cholangiocarcinoma treated over a 28-year period were studied to determine
      demographics, clinical features, laboratory findings, diagnostic tests, operative
      management, and results of therapy. Survival was analyzed according to three
      treatment groups: conservative management, palliative operation, and hepatic
      resection. Conservative management was used for 15 patients, and hepatic
      resections were performed in 39 patients. The remaining 23 patients had
      laparotomy alone (10 patients), bile duct intubation (4 patients), hepatic artery
      ligation (3 patients), bilienteric bypass (3 patients), gastrojejunostomy (1
      patient), insertion of a hepatic artery port for regional chemotherapy (1
      patient), or open drainage of an abscess (1 patient). The median survival after
      conservative management, palliative operation, and hepatic resection were 1.8,
      2.9, and, 12.2 months, respectively. After hepatic resection, patients without
      lymphatic permeation (p < 0.02) or hilar nodal metastases (p < 0.0003) survived
      significantly longer. We concluded that hepatic resection is indicated for
      intrahepatic cholangiocarcinoma when it is deemed resectable.

PMID- 9015176
TI  - Management of pancreatic lesions in von Hippel-Lindau disease.
AB  - Twelve patients with von Hippel-Lindau disease were collected in our institute
      from 1981 to 1995. All had a family history of the disease. Eleven patients
      underwent abdominal computed tomography, sonography, or angiographic studies. Ten
      had pancreatic involvement that included cystic lesions in nine and a solid
      lesion in one. Seven patients were asymptomatic. Another three presented with
      obstructive jaundice or upper gastrointestinal (UGI) bleeding. Except for case 8,
      who died of a central nervous system complication soon after diagnosis of the
      pancreatic lesion, the other patients had been found to have pancreatic
      involvement for a variable period of time, ranging from 1 to 13 years (median 5
      years). Serous cystadenoma was proved pathologically in two with cystic lesions,
      and pancreatic endocrine tumor was diagnosed in one with a solid mass. One
      patient (case 1) underwent biliary bypass due to obstructive jaundice and died of
      cholangitis and pneumonia 6 years later. One patient (case 3) had total
      pancreatectomy and lived well with good diabetic control for more than 5 years.
      The patient with a solid lesion was explored because of repeated UGI bleeding.
      Surgical resection was impossible owing to advanced tumor with vascular
      involvement, and a pancreatic endocrine tumor was diagnosed pathologically. He
      was followed for 1 year. The other seven patients remained asymptomatic during
      the successive follow-up period. From a literature review and our own experience,
      we suggest that conservative measures are adequate for the cystic lesions;
      however, aggressive resection is mandatory for a solid pancreatic lesion in von
      Hippel-Lindau disease.

PMID- 9015177
TI  - Incidence of acute nonperforated and perforated appendicitis: age-specific and
      sex-specific analysis.
AB  - This prospective study was performed to investigate epidemiological
      characteristics in terms of the age- and sex-specific incidence in patients with
      perforated and nonperforated appendicitis. The study population comprised 1486
      consecutive patients who underwent appendectomy for suspected acute appendicitis
      between 1989 and 1993. Two patient cohorts [n = 544 (37%)] were analyzed with
      regard to prehospitalization duration of symptoms and in-hospital observation
      time. The crude incidence of acute appendicitis was 86 per 100,000 per year.
      Although the incidence of nonperforated appendicitis was highest among
      adolescents and young adults (13-40 years of age), perforated appendicitis
      occurred at almost the same incidence in all sex and age groups. The diagnostic
      accuracy was 76%. Perforated appendicitis occurred in 19%, with higher rates in
      small children and the elderly, irrespective of gender. A high diagnostic
      accuracy was not associated with an increased rate of perforation. In small
      children and the elderly, the diagnostic accuracy was low and the perforation
      rate high. Patients with perforation had a significantly longer duration of
      symptoms as well as in-hospital observation time than did patients with
      nonperforated appendicitis. Perforated appendicitis showed a different incidence
      pattern than nonperforated appendicitis and was associated with a significantly
      longer duration of symptoms and in-hospital observation time, probably due to
      patient-related factors. We suggest this observation deserves attention regarding
      clinical diagnosis and treatment decision-making for patients with suspected
      acute appendicitis.

PMID- 9015178
TI  - High stroke volume para-aortic counterpulsation device versus centrifugal pump in
      cardiogenic shock: experimental study.
AB  - During the last decades a number of left ventricular assist devices has been used
      especially for patients resistant to pharmacologic treatment and to intraaortic
      balloon pump (IABP) support for left ventricular failure. A high stroke volume
      para-aortic counterpulsation device (PACD) has been developed utilizing the
      principle of the diastolic counterpulsation technique. In this study the
      hemodynamic effects of the valveless PACD were compared to those of the
      centrifugal blood pump (CBP) in nine dogs in acute experimental cardiogenic
      shock. Hemodynamic measurements were obtained at baseline with both devices off,
      PACD on and CBP off, or PACD off and CBP on. There was no difference in mean
      aortic pressure between PACD on (60.0 +/- 11.5 mmHg) and CBP on (69.0 +/- 26.8
      mmHg). Similarly, there was no difference in left ventricular end-diastolic
      pressure with the PACD on (11.9 +/- 5.4 mmHg) versus the CBP on (9.9 +/- 5.2
      mmHg) or the cardiac index with the PACD on (84 +/- 36 ml/kg/min) versus the CBP
      on (77 +/- 36 ml/kg/min). However, the left ventricular systolic pressure (55.0
      +/- 19.0 with PACD versus 73.0 +/- 26.0 with CBP,p < 0.001), the tension time
      index (712 +/- 381 versus 1333 +/- 694,p < 0.01), and the double product (5629 +/
      2574 versus 7440 +/- 3294,p < 0.01) were significantly lower during assistance
      with the PACD than with the CBP. It was concluded that PACD is at least as
      effective as CBP for restoring hemodynamic status during acute experimental
      cardiogenic shock. Moreover, the PACD unloads the left ventricle more effectively
      than CBP, making it suitable for left ventricular mechanical support in cases
      with reversible myocardial damage.

PMID- 9015179
TI  - Prognostic value of flow cytometric DNA analysis in non-small-cell lung cancer:
      rationale of sequential processing of frozen and paraffin-embedded tissue.
AB  - The objective of this study was to determine the prognostic information provided
      by flow cytometric DNA analysis in non-small-cell lung cancer. Lung samples of
      132 consecutive patients submitted to surgery were prospectively processed. When
      no aneuploid populations were detected in fresh frozen samples, the process
      continued as a second step in paraffin-embedded tissue, consuming all the tumor
      available. The influence of ploidy on the postoperative outcome was studied by
      both a univariate and a multivariate analysis. Aneuploidy was found in 81
      patients (61.4%). Fourteen patients showed no aneuploidy in fresh frozen samples;
      and only after further analysis in paraffin-embedded tissue was abnormal DNA
      detected. Overall, the 36-month survival was 69% for the diploid group and 24%
      for the aneuploid group (p = 0.0006). Including subjects submitted to complete
      tumor removal (stages I, II, and IIIA) in a multivariate analysis adjusted for
      TNM stage and histologic type, bearers of aneuploid tumors exhibited a higher
      risk of relapse (hazard ratio 2.65; CI 95% 1.5-4.66;p = 0.004) or death (hazard
      ratio 2.17; CI 95% 1.08-4.39;p = 0.032) than patients with diploid tumors. DNA
      ploidy resulted an independent prognostic factor of survival and tumor relapse in
      completely resected non-small-cell lung cancer. Sequential analysis of fresh and
      paraffin-embedded samples can help avoid the bias due to intratumoral DNA content
      heterogeneity. DNA ploidy could be an useful parameter in any future
      multifactorial analysis of outcome in such tumors.

PMID- 9015180
TI  - Hepatic surgery and hepatic surgical anatomy: historical partners in progress.
AB  - Whether for hepatic trauma or transplantation, a surgeon's knowledge of hepatic
      anatomy commonly determines a patient's outcome. The first medically relevant
      anatomic studies of the liver emerged with the endeavors of Herophilus and
      Erasistratus between 310 and 280 bc. Yet it was not until after the development
      of anesthesia and antisepsis that the first formal resections were performed
      during the late 1800s. After vascular occlusion principles had been developed as
      a means of successful hemorrhage control, several deliberate attempts were made
      to repair the liver surgically. Such efforts culminated in the work of Wendel in
      1910 when he followed avascular planes during hepatectomy. The functional anatomy
      of surgery and surgical technique had suddenly joined in an effort to advance the
      practice, and eventually the efficacy of hepatic surgeons in facilitating the
      modern era of segmental anatomy extended hepatectomies and transplantation
      surgery.

PMID- 9015181
TI  - Gazelle herpesvirus 1: a new neurotropic herpesvirus immunologically related to
      equine herpesvirus 1.
AB  - A herpesvirus was isolated from Thomson's gazelle (Gazella thomsoni) kept at a
      zoological garden in Japan during an outbreak of epizootic acute encephalitis.
      The virus, gazelle herpesvirus 1 (GHV-1), was serologically related to equine
      herpesvirus 1 (EHV-1). However, DNA fingerprints of GHV-1 were different from
      those of EHV-1 and other equine herpesviruses. Southern hybridization with probes
      of cloned BamHI fragments derived from UL and US segments of EHV-1 revealed
      differences in the DNA restriction profiles throughout the entire genome.
      Nucleotide sequences were determined for a conserved region of an essential
      envelope glycoprotein B (gB) gene and a type-specific glycoprotein G (gG)
      homologue gene. The predicted amino acid sequence of GHV-1 gB showed 97, 92, 61,
      and 57% identity to EHV-1, EHV-4, feline herpesvirus, and pseudorabies virus,
      respectively, indicating that GHV-1 was closer to EHV-1 than any other
      herpesvirus. The GHV-1 gG gene showed 93.2, 92.3, and 53% identity to EHV-1, EHV
      8, and EHV-4 gGs, respectively. GHV-1 was virulent to suckling mice of the ICR
      strain by intracerebral inoculation and was virulent to 4-week-old BALB/c mice by
      intranasal inoculation, causing neurological symptoms and death. We conclude that
      GHV-1 is a new type of equine herpesvirus with strong neurotropism.

PMID- 9015182
TI  - Physical association of CD4 and CD45 in primary, resting CD4+ T cells.
AB  - CD45 is a family of transmembrane protein tyrosine phosphatases that are
      essential to T lymphocytes' responses to antigen-receptor stimulation. It is
      involved in the regulation of Src-family protein tyrosine kinases, Lck and Fyn.
      The object of this study was to determine how CD45 molecules are directed to such
      substrates at the antigen-receptor complex upon stimulation of resting T cells.
      We demonstrate that CD45 is physically associated with CD4 in resting, primary
      lymph node T cells. Further, CD4-dependent, antigen-mediated activation of
      primary CD4+ T cells results in disruption of CD4-CD45 complexes, suggesting a
      role for these complexes in the activation process. Moreover, CD45 coprecipitates
      with CD4 molecules which are associated with Lck, as well as with those which are
      not associated with Lck. Consistent with these observations and the role of CD45
      in the regulation of Lck function, effects on CD4-associated membrane Lck are
      demonstrable. Since antigen presentation by MHC class II results in the
      coaggregation of CD4 with the antigen-receptor complex, the association described
      in this study provides a physical basis through which CD45 could be included.

PMID- 9015183
TI  - T-cell-independent antiviral B cell responses in CD45-deficient mice.
AB  - CD45 is expressed on all B cells and has been reported to be essential for their
      B cell receptor mediated stimulation. The present study addressed T-cell
      independent B cell responses in CD45-deficient mice using the glycoprotein (G) of
      vesicular stomatitis virus (VSV) as a model antigen. VSV-G exists in two forms
      exhibiting different degrees of repetitiveness. In mice, the two forms of VSV-G
      induce either a type 1 or a type 2 T-cell-independent B cell response. We found
      that CD45-deficient mice mounted T-cell-independent B cell responses to both
      forms of VSV-G. This demonstrates that the B cell receptor complex is able to
      generate a functional signal in the absence of CD45, provided the cross-linking
      stimulus is sufficiently strong.

PMID- 9015184
TI  - Normal human keratinocytes inhibit the proliferation of unprimed T cells by
      TGFbeta and PGE2, but not IL-10.
AB  - Recent investigations in antigen processing suggest that many hematopoietic and
      nonhematopoietic cell types are capable of presenting alloantigen to T
      lymphocytes. However, the role of certain nonclassical antigen presenting cells
      is blurred by their apparent ability to down-regulate the immune response as well
      as activate immune cells, depending upon the microenvironment and the functional
      state of the responding cells. In this study we examine the ability of cultured
      allogeneic keratinocytes to inhibit the response of naive T cells to alloantigen
      or to anti-CD3. Our results demonstrate that as few as 6.25 x 10(3) keratinocytes
      significantly inhibited T cell proliferation in response to alloantigen as well
      as anti-CD3-mediated stimulation (49 and 54%, respectively). HK-mediated
      inhibition of T cell proliferation did not require cell contact, suggesting that
      inhibition is mediated by cytokines or other soluble factors. This was further
      supported by experiments demonstrating the inducibility of HK inhibitory activity
      in the presence of FCS, and the partial blockage of HK inhibitory activity
      through the addition of indomethacin or anti-TGFbeta antibody. Interestingly, the
      data suggest that IL-10, a known immunomodulatory cytokine, does not play a role
      in the inhibitory activity seen in this system. Taken together the results
      suggest that HK have the potential to regulate the response of T cells to antigen
      presented by other APC through the production of soluble factors.

PMID- 9015185
TI  - Allogeneic heart transplantation activates alloreactive NK cells.
AB  - The ability of natural killer (NK) cells to recognize and reject transplants has
      so far been shown in hematopoietic grafts only. This study was designed to
      ascertain whether NK cells may also be involved in the rejection of transplanted
      organs. In most rat strain combinations, immunization with allogeneic cells
      induces a T cell response with cytotoxic T lymphocyte (CTL) activation. We have
      previously found one exception to this. In contrast to Wistar Furth rats (WF,
      RT1u), which manifest allospecific CTL activation in response to immunization
      with Brown Norway (BN, RT1n) cells, BN rats immunized with repeated
      intraperitoneal (i.p.) injections of allogeneic WF spleen cells manifest
      activation of alloreactive NK effector cells. The alloreactive NK cells were of
      the TCR-, CD3-, CD8+, and NKR-P1 intermediate phenotype and killed target cells
      with alloselectivity. In this study we used a heart transplantation model to
      study the rejection response of BN rats receiving WF grafts. NK cell infiltration
      was greater in WF hearts transplanted to BN recipients than in BN hearts
      transplanted to WF recipients. Furthermore, the extent of T cell infiltration was
      less in BN recipients. In WF rats transplanted with allogeneic BN hearts, CTL
      were activated in response to i.p. challenge with allogeneic BN cells, whereas BN
      rats transplanted with allogeneic WF hearts and i.p. challenged with allogeneic
      WF cells, manifested activation of alloreactive NK cells but no measurable
      activation of classic CTL. The alloreactive NK cells killed their allogeneic
      targets with specificity and with potency comparable to that of CTL. Furthermore,
      WF grafts were rejected in BN recipients as efficiently as were BN grafts in WF
      recipients. These results not only show cardiac allografts to be able to activate
      alloreactive NK cells, but also suggest that NK cells may be involved in the
      rejection of solid organ transplants and function as classic CTL in certain donor
      recipient combinations.

PMID- 9015186
TI  - Comparison of IL-13- and IL-4-induced signaling in EBV-immortalized human B
      cells.
AB  - Interleukin 4 (IL-4) and Interleukin 13 (IL-13) have been shown to have numerous
      similar effects on human B cells; however, the mechanism of signal transduction
      is not known. We have examined IL-4- and IL-13-induced signal transduction in
      Epstein-Barr virus (EBV)-immortalized B cells. We demonstrate that Janus kinase 3
      (JAK3) and Tyk2 but not JAK1 and JAK2 tyrosine kinases were constitutively
      phosphorylated in three EBV B cell lines. The phosphorylation level of Tyk2 was
      augmented at a low level in response to IL-13 and IL-4 in two of three cell
      lines; however, IL-13 did not induce or augment phosphorylation of the other JAK
      kinases. On the other hand, IL-4 further augmented phosphorylation of JAK3 and
      induced the phosphorylation of JAK1 kinases. IL-4 receptor p140 protein was also
      constitutively phosphorylated in two of three EBV B cell lines examined and both
      IL-4 and IL-13 further augmented its phosphorylation. Insulin receptor substrate
      (IRS)-1 or IRS-2 proteins were not constitutively phosphorylated nor did IL-13
      and IL-4 induce phosphorylation of these proteins. In contrast to JAKs, IL-4
      specific signal transducer and activator of transcription (STAT6) was not
      constitutively phosphorylated or activated in these cell lines, but both IL-4 and
      IL-13 induced their phosphorylation and activation. These findings suggest that
      in EBV-immortalized B cells JAK3 and Tyk2 proteins were constitutively
      phosphorylated but STAT6 protein was not constitutively phosphorylated. In
      addition, despite major similarities in biological effects between IL-4 and IL
      13, phosphorylation patterns of JAK kinases in response to IL-13 in EBV
      immortalized B cells appear to be different from those of IL-4.

PMID- 9015187
TI  - Impaired induction of c-fos/c-jun genes and of transcriptional regulatory
      proteins binding distinct c-fos/c-jun promoter elements in activated human T
      cells during aging.
AB  - The activation of transcriptional factor c-Fos/c-Jun AP-1 is essential for normal
      T cell responsiveness and is often impaired in T cells during aging. In the
      present study, we investigated whether aberrancies in the regulation of c-fos/c
      jun at the mRNA or protein level might underlie the age-associated impairments of
      AP-1 in human T cells. Whereas T cells from young subjects stimulated with cross
      linked anti-CD3epsilon mAb OKT3 plus PMA or with the lectin PHA plus PMA
      demonstrated considerable increases in c-Fos protein expression, the expression
      of c-Fos but not c-Jun was markedly reduced in stimulated T cells from certain
      elderly subjects. In addition, RNase protection assays revealed that anti-CD3/PMA
      stimulated T cells from a substantial proportion of elderly subjects exhibited
      decreased levels of c-fos and/or c-jun mRNA compared to T cells from young
      subjects. Using electrophoretic mobility shift assays, the levels of nuclear
      regulatory proteins recognizing the AP-1 consensus TRE motif, the proximal c-jun
      TRE-like promoter element, and the c-fos serum response element (SRE) were
      determined in resting and stimulated T cells. Although the stimulation of T cells
      from young subjects resulted in coordinated increases of nuclear protein
      complexes binding the AP-1 TRE, c-jun TRE, and c-fos SRE DNA sequence motifs, age
      related reductions in the activation of AP-1 were accompanied by decreased levels
      of c-jun TRE and c-fos SRE binding complexes. Furthermore, the nuclear protein
      complexes binding the SRE motif induced in activated T cells of young and elderly
      subjects contained serum response factor and Elk-1 pointing toward age-related
      defects in the activation of transcriptional regulatory proteins distinct from c
      jun/AP-1. These results suggest that underlying aberrancies in the induction of c
      fos/c-jun as well as their nuclear regulatory proteins may contribute to the age
      related impairments of AP-1 activation in human T cells.

PMID- 9015188
TI  - Differential tyrosine phosphorylation of zeta chain dimers in mouse CD4 T
      lymphocytes: effect of age.
AB  - Antibody to the zeta chain of the CD3/TCR signal transduction complex
      precipitates a series of tyrosine-phosphorylated proteins that can be
      discriminated by electrophoresis in nonreducing polyacrylamide gels. Stimulation
      of resting mouse splenic CD4 T cells by cross-linking CD3 to CD4 leads to
      increases in tyrosine phosphorylation of five such proteins, of which three are
      likely to be dimeric forms of zeta as judged by behavior on two-dimensional gels.
      Two other phosphoproteins, of MW 38 and 55 kDa, also coprecipitate with the
      CD3zeta complex. The level of induced phosphorylation of each of these five
      stimulus-responsive phosphoproteins declines with donor age, T cells from 18
      month-old mice being almost wholly nonresponsive. Resting T cells have only a
      single major form of tyrosine-phosphorylated zetazeta. Phosphorylation of this
      rapidly migrating species is not influenced by activation, but is about threefold
      lower in resting T cells from 12- to 18-month-old mice than in cells from 6-month
      old animals. Thus the phosphorylation of the CD3-zeta chain of CD4 T cells from
      aged mice exhibits abnormalities both in the resting state and within the first 5
      min of the activation process.

PMID- 9015189
TI  - Expression of functional ICAM-1 and VCAM-1 adhesion molecules by an immortalized
      epithelial cell clone derived from the small intestine.
AB  - The role of small bowel-derived epithelial cells in regulating the accumulation
      of inflammatory cells within the inflamed gut epithelium is poorly understood
      because of the difficulties in culturing the epithelial cells in vitro. We have
      recently developed a cloned epithelial cell line (IEC-4.1) derived from the small
      intestine of BALB/c mice. In the present study, we examined whether IEC-4.1 cells
      could express adhesion molecules ICAM-1 and VCAM-1 and the molecular basis of
      macrophage adhesion to the epithelial cells. Northern blot analysis demonstrated
      that IEC-4.1 cells constitutively expressed ICAM-1 and VCAM-1 mRNA at low levels.
      Stimulation with LPS (12 microg/ml) or TNF-alpha (2.5 ng/ml) markedly upregulated
      ICAM-1 and VCAM-1 gene expression in IEC-4.1 cells. ICAM-1 mRNA started to
      increase 2 hr after LPS stimulation, peaked at 4 hr, and then decreased rapidly
      to the basal level at 8 hr. VCAM-1 mRNA had the similar pattern of upregulation
      but the increased VCAM-1 mRNA sustained over a longer period of time and did not
      return to the basal level until 24 hr after the stimulation. IEC-4.1 cells
      expressed very low basal levels of ICAM-1 and VCAM-1 on the cell surface as
      demonstrated by immunofluorescence staining and FACS analysis. Stimulation of IEC
      4.1 cells with LPS or TNF-alpha markedly increased the surface expression of both
      ICAM-1 and VCAM-1, which correlated with the increased binding of macrophages to
      the stimulated IEC-4.1 cells. Adherence of macrophages to the IEC-4.1 cells was
      mediated by both LFA-1/ICAM-1 and VLA-4/VCAM-1 since blocking both adhesion
      pathways inhibited macrophage adhesion by about 90%. These findings suggest that
      small bowel-derived epithelial cells may be capable of expressing a defined set
      of functional adhesion molecules during mucosal inflammation.

PMID- 9015190
TI  - Clonal anergy is a potent mechanism of oral tolerance in the suppression of acute
      antigen-induced arthritis in rats by oral administration of the inducing antigen.
AB  - The effects of oral administration of ovalbumin (OVA) on acute OVA-induced
      arthritis (OIA) in rats, which is mediated by Arthus reaction to the antigen in
      the joint space, were investigated. The oral administration of OVA before
      immunization with OVA significantly suppressed the development of acute OIA in a
      dose-dependent manner, in accordance with decreases in both the in vivo anti-OVA
      IgG antibody production and in vitro lymphocyte proliferative responses to OVA.
      These results were shown in both the single high-dose (200 mg x 1) or the
      multiple low-dose (200 microg x 5) feeding protocols. In vitro study showed that
      rat IL-2 could reverse the reduced OVA-specific lymphocyte proliferative
      responses. The spleen cells obtained from OVA-feeding, unprimed rats neither
      adoptively transferred the suppression to naive recipient rats nor suppressed the
      in vitro lymphocyte proliferation. These results demonstrate that the acute OIA
      can be suppressed by the induction of oral tolerance (OT) to OVA, and strongly
      suggest that the OT was due to clonal anergy of antigen-reactive T lymphocytes,
      not the active suppression by OVA-specific regulatory cells.

PMID- 9015191
TI  - Alteration of platelet-activating factor-induced signal transduction in
      macrophages by n-3 fatty acids.
AB  - Diets rich in polyunsaturated n-3 fatty acids can alter various macrophage
      functions. One possible mechanism by which this occurs is through modulation of
      the physicochemical properties of the cell membrane and the signal transduction
      pathways associated with macrophage activation. In this study, we investigated
      how n-3 fatty acids altered the signaling pathway of the lipid-based mediator
      platelet-activating factor (PAF). Macrophages from mice fed a diet containing n-3
      fatty acids showed a greater increase in PAF-induced intracellular Ca2+
      mobilization than macrophages from mice fed an n-6 fatty acid-rich diet.
      Macrophages treated in vitro with the n-3 fatty acids docosahexaenoic and
      eicosapentaenoic also showed higher intracellular Ca2+ mobilization than
      untreated or n-6 fatty acid-treated macrophages. Scatchard analysis of PAF
      binding showed the presence of one type of PAF receptor; their number and
      affinities were not altered by dietary fat. Mastoparan, which can activate G
      protein-linked phosphoinositide (PI)-signaling pathway through the activation of
      G proteins, stimulated a higher Ca2+ mobilization in macrophages from mice fed n
      3 compared to n-6 fatty acids. In addition, the response of macrophages from n-3
      fed mice to PAF was less sensitive to phospholipase C inhibition than that of
      macrophages from those fed n-6 diets. The activity of phospholipase C in
      macrophages from mice fed n-3 diets was significantly higher than that of
      macrophages from mice fed diets containing n-6 fatty acids. Collectively, these
      results showed that n-3 fatty acids can enhance the PAF-signaling pathway in
      macrophages by increasing the activation potential of phospholipase C, without
      affecting PAF receptor number and affinity.

PMID- 9015192
TI  - CD10 (endopeptidase 24.11) is a thymic peptide-degrading enzyme possibly involved
      in the regulation of thymocyte functions.
AB  - Human immature thymocytes express significant levels of the CD10 (endopeptidase
      24.11) cell surface antigen. We report here that IOB5, an anti-CD10 mAb, as well
      as the phorbol ester PMA down-regulate CD10 activity at the surface of human
      thymocytes. The kinetics of CD10 modulation were drastically different for both
      effectors, indicating different regulatory mechanisms. We also demonstrated that
      intact human thymocytes hydrolyze thymopentin and that CD10 significantly
      participates in this process. Finally, we found that thymopentin and to a lesser
      extent phosphoramidon, a specific endopeptidase 24.11 inhibitor, induced up
      regulation of CD4 and CD8 molecules at the thymocyte cell surface. In view of
      these results, we suggest that down-regulation of endopeptidase 24.11 at the
      thymocyte cell surface might reduce its activity toward thymic factors possibly
      involved in the regulation of thymocyte functions.

PMID- 9015193
TI  - Experimental allergic encephalomyelitis and vaccination-induced resistance in DA
      rats.
AB  - In this report, we show that DA rats (RT1a haplotype) immunized with myelin basic
      protein (MBP)-CFA develop and recover from an ascending paralysis, with the
      course and severity of clinical disease similar to the kinetics observed with MBP
      CFA-immunized Lewis rats. Experimental allergic encephalomyelitis (EAE) can be
      adoptively transferred with MBP-stimulated immune spleen cells, with onset of
      paralysis 4 days following transfer and complete recovery 3-4 days later. To
      determine if the vaccination-induced resistance response could develop in the DA
      rat strain, which has previously been shown to occur only in the Lewis rat, we
      selected a MBP-specific T-cell line by standard methods from DA rats immunized
      previously with MBP-CFA. The DA T-cell line was encephalitogenic, and DA
      recipients developed and recovered from T-cell line-mediated paralytic disease.
      Following recovery from T-cell line-mediated disease, DA recipients were
      resistant to subsequent disease induction following MBP-CFA challenge, a response
      consistent with T-cell vaccination, as observed previously in Lewis rats.
      Analysis of the proliferative response of the DA T-cell line showed that the
      encephalitogenic fragment was within the 40-67 region of MBP, with no response to
      the 85-97 fragment. The 85-97 fragment, which is a minor encephalitogenic
      determinant for the Lewis strain, also appears to be a minor encephalitogenic
      epitope for DA rats. These results show that the vaccination-induced resistance
      response occurs in the DA rat strain and that this phenomenon is not unique to
      the Lewis rat model.

PMID- 9015199
TI  - Vinculin and talin: kinetics of entry and exit from the cytoskeletal pool.
AB  - Vinculin and talin, two major components of focal contacts, exist in cytosolic
      and cytoskeletal pools. The kinetics of entry and exit of the two proteins
      between the two pools were investigated in normal and transformed cells. In
      cultured chick embryo fibroblasts, a fraction (2-5%) of the newly synthesized
      vinculin and talin reached maximal levels in the cytoskeleton in 30-45 min. Both
      proteins had 2-3 times shorter half-lives in the cytoskeletal pool (t1/2 = 6-7 h)
      than in the cytosolic pool (t1/2 = 14-15 h), which suggests that the
      incorporation of cytosolic vinculin and talin into the cytoskeleton does not
      involve a simple equilibrium between the two pools. However, after disruption of
      cell-to-substrate adhesion by trypsinization, an equilibrium in the incorporation
      between the two pools was transiently established, resulting in the use of the
      preexisting cytosolic pools of the two proteins during re-establishment of cell
      to-matrix contacts. Viral transformation did not cause a significant change in
      the incorporation rates into the cytoskeleton. However, it decreased the half
      lives of both proteins in the cytoskeletal pool (t1/2 = approximately 4 h) and in
      the cytosolic pool (t1/2 = 9-10 h). The increased turn-over rates of vinculin and
      talin in the cytoskeletal pool in transformed cells may contribute to the
      enhanced motility of transformed cells.

PMID- 9015200
TI  - Cytochalasin J treatment significantly alters mitotic spindle microtubule
      organization and kinetochore structure in PtK1 cells.
AB  - It has previously been demonstrated that treatment of mitotic PtK1 cells with 10
      20 microg/ml cytochalasin J (CJ) blocks or slows chromosome motion and has a
      significant effect on spindle architecture [Snyder and Cohen, 1995: Cell Motil.
      Cytoskeleton 32:245-257]. Spindle microtubules (MTs) were shown to reorganize
      within the spindle domain, with kinetochore MTs (kMTs) reduced in number and non
      kinetochore MTs (nkMTs) shown to splay outside the original spindle domain. In
      some cases, bundles of MTs were shown to be refocused away from the original
      spindle poles, creating the appearance of a multi-polar spindle. In this paper we
      use serial section electron microscopy, coupled with computer-assisted
      reconstruction techniques, to determine the rearrangement of spindle MTs and
      chromosome position following brief treatments of mitotic cells with 10-20
      microg/ml CJ at various stages of mitosis. CJ treatment of prometaphase cells
      reduces the number of kMTs and the size and organization of the kinetochore
      lamina. Instead of kinetochore bundles of MTs aligned parallel to one another and
      running from kinetochore to pole, this class of MTs is highly fragmented. Non
      kinetochore MTs are also highly fragmented, usually less than 2 microm long, and
      remain relatively straight over short distances, with some MTs arranged at an
      oblique angle to the longitudinal spindle axis. In approximately 30% of cells
      treated with CJ, the failure of a small number of chromosomes to attach to
      spindle fibers can be documented. These chromosomes show a significant change in
      the organization of the kinetochore laminae. Light microscopic analysis of cells
      treated with CJ reveals loss of chromosome congression, with chromsomes usually
      located at the periphery of the spindle and some completely detached from the
      spindle. Cells treated with 10 microg/ml CJ for 10 min and released into tissue
      culture medium show a resumption of chromosome motion within a few minutes, both
      during congression and anaphase. Where kMTs are inserted into kinetochores,
      chromosome motion is seen; where chromosomes fail to attach to the spindle, no
      chromosome motion is observed. Cells treated in metaphase show a delayed entry
      into anaphase and a reduced rate of anaphase A, with the arms of some chromosomes
      remaining in the interzone region. Our results suggest that CJ-sensitive
      molecules play a role in the organization of spindle MTs, as well as their
      functional association to kinetochores.

PMID- 9015201
TI  - How calcium causes microtubule depolymerization.
AB  - The effects of calcium (Ca) were assessed using video-enhanced differential
      interference contrast light microscopy on individual microtubules in vitro.
      Phosphocellulose-purified (PC) and microtubule associated protein (MAP)
      containing preparations of porcine brain tubulin were assembled in a flow chamber
      onto sperm axoneme fragments and the pattern of growth and shortening of the
      microtubules was observed. Tubulin plus Ca was then added to the chamber and
      observation continued. Ca promoted the disassembly of microtubules by
      specifically promoting the catastrophe reaction in both PC- and MAP-containing
      microtubules, without an appreciable change in elongation rate. The effect on
      catastrophe frequency increased very rapidly above 0.5 mM free Ca, implying a
      possible cooperative effect. The rescue rate remained very high after Ca addition
      in MAP-containing microtubules, and the shortening rate was unchanged, while in
      phosphocellulose-purified microtubules, rescue appeared to be decreased by Ca
      addition and shortening rates increased 4 to 6-fold. These results illustrate
      that Ca can directly destabilize growing microtubule ends without changing the
      effective concentration of free tubulin, and that this effect can be seen even
      against the background of the profound differences in dynamics conferred by the
      microtubule-associated proteins. Considered within models of the GTP cap, the
      results imply that high Ca may act to increase the rate of GTP hydrolysis within
      the cap.

PMID- 9015202
TI  - Ultraviolet microbeam irradiations of epithelial and spermatocyte spindles
      suggest that forces act on the kinetochore fibre and are not generated by its
      disassembly.
AB  - Ultraviolet (UV) microbeam irradiations of crane-fly spermatocyte and newt
      epithelial spindles severed kinetochore fibres (KT-fibres), creating areas of
      reduced birefringence (ARBs): the remnant KT-fibre consists of two "stubs," a
      pole-stub attached to the pole and a KT-stub attached to the kinetochore. KT
      stubs remained visible but pole-stubs soon became undetectable [Forer et al.,
      1996]. At metaphase, in both cell types the KT-stub often changed orientation
      immediately after irradiation and its tip steadily moved poleward. In
      spermatocytes, the chromosome attached to the KT-stub remained at the equator as
      the KT-stub elongated. In epithelial cells, the KT-stub sometimes elongated as
      the associated chromosome remained at the equator; other times the associated
      chromosome moved poleward together with the KT-stub, albeit only a short distance
      toward the pole. When an ARB was generated at anaphase, chromosome(s) with a KT
      stub often continued to move poleward. In spermatocytes, this movement was
      accompanied by steady elongation of the KT-stub. In epithelial cells, chromosomes
      accelerated polewards after irradiation until the KT-stubs reached the pole,
      after which chromosome movement returned to normal speeds. In some epithelial
      cells fine birefringent fibres by chance were present along one edge of ARBs;
      these remnant fibres buckled and broke as the KT-stub and chromosome moved
      polewards. Similarly, KT-stubs that moved into pole stubs (or astral fibres)
      caused the pole stubs (or astral fibres) to bend sharply from the point of
      impact. Our results contradict models of chromosome movement that postulate that
      force is generated by the kinetochore disassembling the KT-fibre. Instead, these
      results suggest that poleward directed forces act on the KT-fibre and the KT-stub
      and suggest that continuity of microtubules between kinetochore and pole is not
      obligatory for achieving anaphase motion to the pole.

PMID- 9015203
TI  - Role of NCAM, cadherins, and microfilaments in cell-cell contact formation in TM4
      immature mouse sertoli cells.
AB  - To determine events that lead to the formation of intercellular contacts, we
      examined the spatial and temporal distribution of NCAM, cadherins, and F-actin in
      TM4 cells by immunofluorescence and laser scanning confocal microscopy. TM4 cells
      exhibited epithelioid characteristics and formed large overlapping lamella-like
      cell-cell contacts that contained a high concentration of NCAM. NCAM-rich
      lamellae formed from smaller NCAM patches at the ends of filopodia-like contacts
      between adjacent cells. Cadherins, as visualized by a pan-cadherin antibody, were
      present in a pattern distinctly different from that of NCAM. Although in
      filopodia-like contacts, both cadherins and NCAM were often concentrated at
      filopodial tips, in the larger lamella-like contacts that developed later,
      cadherins were located in an irregular punctate pattern only at the distal and
      more apical margins of the slanted NCAM-rich contact regions. Patterns of NCAM
      and microfilament (MF) bundle distribution were distinctly different, suggesting
      that the ends of these MF bundles were not physically linked to NCAM. By
      contrast, cadherins were concentrated at the ends of MF bundles at all stages of
      contact formation examined. Interestingly, this association of cadherins with MF
      bundles was mostly seen at the edge of the overlapping processes. In the lower
      cell process, MF bundles at the contact site were often arranged in random
      fashion, indicating an asymmetric distribution of MF in the junctional region.
      However, N-cadherin was enriched only at sites where MF bundles from both the
      upper and lower cell processes were aligned and terminated at the junctional
      membrane. Thus the organization of the actin cytoskeleton at cell-cell contact
      sites is influenced by the differential localization of different cadherins.
      These data also suggest that different mechanisms are involved in the
      accumulation of NCAM and cadherins in cell-cell contact regions.

PMID- 9015204
TI  - Sequence analysis and immunofluorescence study of alpha- and beta-tubulins in
      Reticulomyxa filosa: implications of the high degree of beta2-tubulin divergence.
AB  - We have cloned and sequenced 2 alpha- and 2 beta-tubulin isoforms from the giant
      freshwater amoeba Reticulomyxa filosa. The microtubules of this organism exhibit
      some unusual properties, including the highest rates of assembly and disassembly
      known and the inability to be stabilized by taxol. The cloned alpha-tubulins show
      a high degree of identity when compared to an alpha-tubulin consensus sequence.
      The beta-tubulins, however, are more divergent, the beta2-tubulin being the most
      unusual beta-tubulin found so far. The deduced amino acid sequence of beta2 shows
      55% identity to a beta-tubulin consensus sequence. It also features 51 unique
      exchanges which cluster in the C-terminal half of the molecule. Several unique
      exchanges and two insertions occur in regions adjacent to, or directly implicated
      in, conserved beta-tubulin functions. A phylogenetic analysis places the beta
      tubulins of R. filosa in the vicinity of beta-tubulins from fungi and slime
      molds. Monoclonal and polyclonal antibodies raised against R. filosa tubulins
      show that the electrophoretic mobility of alpha- and beta-tubulins is reversed
      with respect to tubulins from most other sources. Immunofluorescence experiments
      reveal a ubiquitous distribution of both beta-tubulins in the amoebal network.
      Our observations suggest possible links between the aberrant primary structure of
      the beta2-tubulin and the unusual properties of R. filosa microtubules.

PMID- 9015205
TI  - Protein complexes containing gamma-tubulin are present in mammalian brain
      microtubule protein preparations.
AB  - The presence of gamma-tubulin in microtubule preparations, obtained by
      disassembly/ assembly cycles at 0degreesC/37degreesC from the brain of several
      mammals, is demonstrated by immunoblotting with specific antibodies directed
      against three distinct regions of the protein. In contrast gamma-tubulin was
      absent from pure tubulin obtained by chromatography on phosphocellulose, but was
      retained on the column with the other microtubule-associated proteins. A large
      part of the gamma-tubulin was present in cold stable material remaining after
      microtubule disassembly at OdegreesC and was partially solubilized using high
      salt, thus preventing its purification by the usual assembly/disassembly
      procedure used for alpha/beta-tubulin heterodimers. Brain gamma-tubulin was
      purified by affinity chromatography with gamma-tubulin antibodies raised against
      its carboxyl terminal region. Purified gamma-tubulin consisted of at least two
      polypeptides present in equal quantities and exhibiting a pI of 6.5 and 6.6,
      respectively. It was associated with the alpha/beta-tubulin heterodimer and with
      at least five other polypeptides of 75, 105, 130, 195, and 250 kDa. With the
      exception of the 250 kDa polypeptide, all of these proteins seem to be present in
      gamma-tubulin complexes isolated from Xenopus eggs. But, in contrast with Xenopus
      egg complexes, brain complexes exhibited a considerable heterogeneity of their
      apparent masses and composition in sucrose gradient centrifugation, in agreement
      with the absence of an homogeneous structure in electron microscopy. Despite this
      heterogeneity, gamma-tubulin complexes bind quantitatively to microtubule
      extremities. The possibility to further use mammalian brain gamma-tubulin and
      some of its associated proteins in biochemical and pharmacological experiments is
      of interest since brain microtubule protein preparations have been extensively
      used for studying both microtubule dynamics and the activity of microtubule
      poisons.

PMID- 9015206
TI  - SF-assemblin in Chlamydomonas: sequence conservation and localization during the
      cell cycle.
AB  - Previously, SF-assemblin has been identified as the filament-forming component of
      the striated microtubule-associated fibers (SMAFs), which emerge from the basal
      bodies in several green flagellates. We have sequenced cDNAs coding for SF
      assemblin from Chlalmydomonas reinhardtii and C. eugametos. Comparison of the
      deduced amino acid sequences with the previously described green algal SF
      assemblins shows identities between 54 and 71%, indicating a strong drift in
      sequence. Cells of C. reinhardtii were analyzed by double immunofluorescence
      using polyclonal anti-SF-assemblin and anti-alpha-tubulin. In interphase cells,
      SF-assemblin is associated with all four microtubular flagellar roots. During
      mitosis the SF-assemblin-based cytoskeleton is reorganized; it divides in
      prophase and is reduced to two dot-like structures at each spindle pole in
      metaphase. During anaphase, the two dots present at each pole are connected
      again. In telophase we observed an asymmetrical outgrowth of new fibers. These
      observations suggest a role for SF-assemblin in reestablishing the microtubular
      root system characteristic of interphase cells after mitosis.

PMID- 9015207
TI  - Angiotensin I-converting enzyme, blood groups, and a local marrow-specific renin
      angiotensin system.

PMID- 9015208
TI  - The physico-chemical factors that govern retrovirus-mediated gene transfer.
AB  - The most commonly used vehicle for gene transfer into human target cells is a
      replication incompetent retroviral vector. The efficiency of gene transfer with
      this type of vector has proven to be too low to implement effective gene therapy.
      To date much effort has gone into engineering the genetic and biochemical
      functionalities of retroviral vectors. Although progress has been achieved, high
      efficiency reproducible gene transfer into human cells remains elusive. There are
      many important physico-chemical and systemic kinetic factors that govern the
      process of retrovirus-mediated gene transfer. These factors have gone mostly
      unrecognized to date. The former include the nature of the random Brownian motion
      of the retrovirus and the physico-chemical forces that determine the binding of
      the retroviral vector to the target cell. The latter arise from the kinetics of
      virus binding and entry into the target cell, as well as the kinetic interplay
      between cell-cycle and retroviral life-cycle events that determine the
      intracellular fate of the virus. This review describes these processes and how
      they constrain the efficiency of the gene transfer process.

PMID- 9015209
TI  - Comparative cytokine production by in vitro stimulated mononucleated cells from
      cord blood and adult blood.
AB  - Cord blood transplantations successfully reconstituted hemopoiesis in patients
      treated with myeloablative therapies. These transplantations were associated with
      a low rate of acute graft-versus-host disease (aGVHD), a major life-threatening
      complication of allo-transplantation. The physiopathology of aGVHD implies the
      recognition of host alloantigens by donor T cells but also involves a cytokine
      cascade. In this cascade, interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor
      alpha (TNF-alpha), and interferon gamma (IFN-gamma) produced by donor T cells and
      monocytes/macrophages play a major effector role. Therefore, we investigated
      whether the lower percentage of aGVHD in cord blood transplants could be related
      to a lower ability to produce these cytokines in vitro compared with adult blood.
      Mononucleated cells (MNCs) isolated from term cord blood and adult peripheral
      blood were stimulated with a combination of lipopolysaccharide and
      phytohemaglutinin and incubated for 96 hours. Levels of IL-1beta, IL-2, IL-3, IL
      4, IL-6, TNF-alpha, IFN-gamma, and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) were measured in the supernatants after various times of
      incubation. The productions of IL-1beta, IL-6, and GM-CSF were similar in
      stimulated cord and adult blood and IL-3 levels, though lower and delayed in cord
      blood, were not statistically different. On the other hand, we found markedly
      lower levels of IFN-gamma, TNF-alpha, and IL-4 in cord blood throughout the
      incubation period. The stimulated levels of IL-2 were similar in cord and adult
      samples throughout the first 48 hours of incubation but became significantly
      lower in cord blood after 72 and 96 hours. We suggest that the cytokine
      production pattern that characterizes cord blood could provide an explanation for
      the lower occurence of aGVHD following cord blood transplants.

PMID- 9015210
TI  - Stages in the development of radiation-induced thymic lymphomas in C57 BL/Ka
      mice: preleukemic cells become progressively resistant to the tumor preventing
      effects of a bone marrow graft.
AB  - Fractionated whole body irradiation induces thymic lymphomas in C57 BL/Ka mice
      after 6-12 months. A graft of normal congenic bone marrow cells immediately after
      the last irradiation prevents the development of lymphomas by inducing the
      disappearance of preleukemic cells. When such a graft is performed one month
      later, it does not inhibit the emergence of tumors. It could be because, one
      month after irradiation, preleukemic cells become insensitive to the effects of
      the grafted bone marrow on their leukemogenic potential. To check this
      hypothesis, we have investigated the capacity of grafted bone marrow cells to
      prevent the development of lymphomas in mice inoculated with radiation-induced
      preleukemic cells collected at several time intervals after the completion of the
      radiation regimen. It was found that the bone marrow graft reduced the incidence
      of thymic lymphoma at day 2 (10 vs. 43%; p < 0.01) and 10 (39 vs. 86%; p < 0.01)
      but not at day 15 (64 vs. 80%; NS) or 30 (93 vs. 82%; NS). The inefficacy of the
      marrow graft was not associated with proliferation of the inoculate in the
      recipient thymus nor with inhibition by preleukemic cells of thymic repopulation
      by bone marrow precursors. The data provide evidence that preleukemic cells
      undergo intrinsic changes which are reflected by the acquisition of resistance to
      bone marrow grafts.

PMID- 9015211
TI  - Stem cell transplantation in the normal nonmyeloablated host: relationship
      between cell dose, schedule, and engraftment.
AB  - In previous studies we have shown high rates of stable engraftment when 40
      million male BALB/c cells were infused intravenously daily for 5 days (a total of
      200 million cells) to normal nonmyeloablated female hosts. The present studies
      evaluate engraftment of male BALB/c bone marrow cells in female host marrow,
      spleen, and thymus 20-25 weeks after transplantation using varying cell dosages
      within a 5-day schedule. Engraftment in recipient mice was assessed by detection
      of male specific sequence in recipient DNA from each organ. When 40 million cells
      were given per daily injection for 1, 2, 3, 4, or 5 days, engraftment percentages
      in host marrow were 11 +/- 0.83, 20 +/- 2.0, 23 +/- 2.5, 32 +/- 6.3, and 39% +/-
      5.7 (+/- standard error of mean), respectively, yielding engraftment percentages
      per million cells infused of 0.28, 0.25, 0.19, 0.20, and 0.20%, respectively.
      When levels of 2.5, 5, 10, 20, or 40 million cells were injected 5 times over a 5
      day schedule into normal BALB/c female hosts, progressively increasing levels of
      engraftment from 3 +/- 0.6 to 39% +/- 5.7 were seen in host marrow. Highest
      levels of engraftment per million cells injected were obtained on days 1 and 2 of
      a 5-day schedule and with a level of 10 million cells given daily over 5 days.
      Engraftment profiles varied with spleen and thymus and percent engraftment was
      generally lower than for marrow. The present work indicates that regardless of
      cell level infused or number of infusions, rates of engraftment observed in
      marrow approached or exceeded the highest rates of engraftment estimated by
      theoretical calculations based on replacing host cells ("replacement model") or
      adding to host cells ("incremental model"). Engraftment in spleen and thymus was
      lower, but also at times approached or exceeded theoretical maxima. These data
      show extraordinary levels of engraftment in normal hosts, suggesting that rates
      in this competitive model are superior to those seen in irradiated hosts;
      alternatively, there may be selective repression of host stem cell proliferation
      and differentiation.

PMID- 9015212
TI  - Increased G-CSF responsiveness of bone marrow cells from hematopoietic cell
      phosphatase deficient viable motheaten mice.
AB  - The mouse mutation viable motheaten (me(v)) results in defects in the expression
      and catalytic activity of the cytoplasmic protein tyrosine phosphatase known as
      hematopoietic cell phosphatase (HCP). This reduction in HCP activity leads to the
      aberrant regulation of several myeloid and lymphoid cell lineages, including
      substantial increases in numbers of granulocytes. The differentiation,
      proliferation, and survival of cells in this lineage are normally supported by
      granulocyte-colony stimulating factor (G-CSF). In this study we have determined
      the consequences of the loss of HCP activity in me(v)/me(v) mice on the response
      of bone marrow cells to G-CSF. Bone marrow from these mice exhibited substantial
      increases in clonogenic and proliferative responses to G-CSF. These enhanced
      activities of G-CSF correlated with an increase in the level of immature
      granulocytic, G-CSF receptor positive cells in the bone marrow. These results
      suggested the possibility that HCP may regulate the G-CSF receptor by a direct
      interaction. However, under conditions where the previously described interaction
      between the erythropoietin receptor and HCP was readily observed, HCP did not
      detectably associate with the G-CSF receptor.

PMID- 9015213
TI  - Bone marrow fibroblast exposure to the inflammatory cytokines tumor necrosis
      factor-alpha and interferon-gamma increases adhesion of acute myeloid leukemia
      cells and alters the adhesive mechanism.
AB  - Human acute myeloid leukemia (AML) cells adhere to bone marrow fibroblasts (BMF)
      and extracellular matrix proteins including fibronectin. Adhesion is increased
      when fibroblast monolayers are exposed to tumor necrosis factor-alpha (TNF) alone
      and in combination with interferon-gamma (IFN) or interleukin-4 (IL-4). The
      combination of TNF and IFN caused enhanced AML cell adhesion to treated BMFs,
      from a mean of 25.0 +/- 4.1% to 36.3 +/- 5.4% (p = 0.0007). Enhanced binding was
      partially a result of upregulated vascular cell adhesion molecule-1 expression on
      BMFs. Intercellular adhesion molecule-1 was also upregulated, but did not appear
      to play a role in the increased binding to cytokine-stimulated BMFs. In contrast
      to observed adhesion to resting BMFs, AML cells binding to TNF/IFN-stimulated
      BMFs rely more heavily on the VLA-4 alpha chain (CD49d). In some cases, alpha4
      integrin chain antibody was more effective than beta1 antibody in blocking
      binding, suggesting that a non-beta1 alpha4 integrin, possibly alpha4 beta7, on
      AML cells may act as a stromal ligand. The addition of alpha4 antibody to beta1
      and beta2 antibodies significantly increased the inhibition of AML cells to
      stimulated BMFs. The myeloid cytokines granulocyte colony stimulating factor,
      granulocyte-monocyte colony stimulating factor, interleukin-3 and stem cell
      factor enhanced the adhesion of AML blast cells to BMFs in some cases. The
      phorbol ester PMA, however, consistently upregulated AML cell-binding to BMFs,
      the increase being mediated entirely via beta1 and beta2 integrins without
      altering AML cell integrin expression. Binding of AML cells to marrow stroma can
      be enhanced by influences on leukemic cell or stroma. Enhanced binding under
      these conditions occurs via different pathways, illustrating the heterogeneity of
      mechanisms underlying leukemic cell retention within the bone marrow stroma.

PMID- 9015214
TI  - Production and consumption of the tetrapeptide AcSDKP, a negative regulator of
      hematopoietic stem cells, by hematopoietic microenvironmental cells.
AB  - This study was performed to evaluate the role of human microenvironmental cells
      in the metabolism of AcSDKP, a physiological inhibitor of hematopoietic stem
      cells. Using long-term marrow cultures (LTMCs), whose medium already contained a
      baseline value of AcSDKP, we found after 2 weeks a net output in the culture
      supernatant indicating that release by cells from the adherent layer was superior
      to consumption of the peptide. Since human microenvironmental cells consist of
      macrophages and vascular smooth-muscle-like stromal cells we generated pure
      populations of macrophages (by culturing cord blood cells in the presence of
      granulomonocytic colony-stimulating factor) and of stromal cells (generated by
      stromal colonies). We found in supernatants of macrophage cultures a
      significantly (p < 0.01) increased level of AcSDKP (compared with value in
      medium) while in supernatants of stromal cell cultures the level was decreased.
      Cell content of angiotensin-converting enzyme (ACE) in stromal cells was higher
      than in macrophages, which suggests a degradation of AcSDKP by stromal cells
      because of their higher amount of ACE. Finally, we analyzed the content of AcSDKP
      in adherent layers of LTMCs (with or without extracellular matrix [ECM]
      components), macrophages, and stromal cells. We found levels of AcSDKP of 1.5
      pMol per 106 cells in extracts from macrophages or from stromal cells. On the
      contrary, extracts from primary layers of LTMCs contained 3 times more AcSDKP;
      however, after treatment of primary layers by collagenase, AcSDKP level fell to 1
      pMol per 10(6) cells. Immunofluorescence using an anti-AcSDKP monoclonal antibody
      showed an extracellular network in certain areas of LTMCs. This study shows that
      1) macrophages synthesize and release in the supernatant AcSDKP, 2) stromal cells
      probably degrade the peptide via ACE, and 3) components of the ECM from LTMCs
      serve as a reservoir for the peptide. These results are reminiscent of what has
      been described for growth factors, produced by microenvironmental cells, and
      stored in the ECM in close vicinity to hematopoietic precursors.

PMID- 9015215
TI  - Immune reconstitution with donor-derived memory/effector T cells after orthotopic
      liver transplantation.
AB  - Therapeutic hematopoietic stem cell transplantation has made great strides in
      recent years, providing curative therapy for many previously untreatable
      diseases. Nevertheless, the applicability and effectiveness of this procedure
      continues to be restricted by adverse immunoregulatory states, including graft
      rejection, graft vs. host disease (GvHD), and/or persistent immunodeficiency.
      Here, we provide evidence that long-term hematopoietic stem cell transplantation
      across major histocompatibility complex (MHC) barriers is possible in the human
      with limited adverse sequelae. We observed the rapid, complete, and stable
      replacement of recipient hematopoiesis and B lymphopoiesis with donor-derived
      cells approximately 6 weeks following orthotopic liver transplantation for
      hemochromatosis. Long-term T lineage reconstitution also occurred, but most
      intriguingly, derived almost exclusively from expansion of mature,
      memory/effector T cells from the transplanted liver. Although demonstrating both
      functional and molecular evidence of a simplified T cell receptor (TCR)
      repertoire and unable to become sensitized to "new" antigens (Ag), this patient
      demonstrated long-term clinical immunocompetence. Moreover, the transplanted T
      cells were effectively tolerant to host tissues as the patient did not manifest
      clinically significant GvHD off immunosuppressive therapy. These observations
      suggest that isolated memory/effector T cell populations have the potential of
      promoting stem cell engraftment in an allogeneic host without persistent GvHD,
      and to provide sufficient immune reconstitution to provide the recipient with
      long-term immune homeostasis.

PMID- 9015216
TI  - Dissociation of the Jak kinase pathway from G-CSF receptor signaling in
      neutrophils.
AB  - Activation of the granulocyte colony-stimulating factor receptor (G-CSFR) induces
      rapid tyrosine phosphorylation of multiple intracellular substrates in
      proliferating cells and nonproliferating, terminally differentiated neutrophils.
      The kinases that couple ligand binding to tyrosine phosphorylation of cellular
      substrates by the G-CSFR with activation of specific functional programs are
      largely unknown. In this study, we examined early signaling events in
      proliferating and terminally differentiated cells following G-CSF stimulation to
      determine whether identical signaling cascades are activated. In murine Ba/F3
      cells transfected with the human G-CSFR and NFS-60 cells constitutively
      expressing the murine G-CSFR, G-CSF induced tyrosine phosphorylation and
      activation of Jak1, Jak2, and Tyk2. Tyrosine phosphorylation of Stat3 and, to a
      lesser extent, Stat1 was also detected following G-CSF stimulation. Using a
      mitogenically incompetent human G-CSFR mutant in which Pro639 and Pro641 were
      substituted by alanine, the box 1 PDP motif was found to be required for
      activation of Jak kinases, tyrosine phosphorylation of the G-CSFR, and
      recruitment of Stat proteins. Notably, no activation of Jak1, Jak2, Tyk2, Stat1,
      or Stat3 was observed in neutrophils following G-CSF stimulation. In addition,
      there was no detectable activation in neutrophils of the recently cloned Jak3
      kinase, which has been reported to be expressed at high levels as myeloid cells
      undergo terminal neutrophilic maturation. These results indicate a lack of
      involvement of Jak kinases in signaling by the G-CSFR in neutrophils, and suggest
      utilization of alternative signal transduction pathways distinct from those in
      proliferating cells. Activation of the Jak-Stat pathway correlates with
      proliferative signaling by the G-CSFR and requires the membrane-proximal box 1
      PXP motif, which is conserved in members of the cytokine receptor superfamily.

PMID- 9015217
TI  - Action of thrombopoietin at the megakaryocyte progenitor level is critical for
      the subsequent proplatelet production.
AB  - Formation of proplatelets from megakaryocytes is believed to be the first step of
      platelet production in vitro. In this study, we evaluated the effects of
      recombinant human thrombopoietin (hTPO) on the development of proplatelets from a
      GpIIb/IIIa+ population of rat bone marrow cells highly enriched for late
      megakaryocyte progenitors (GpIIb/IIIa+ CFU-MK) that we recently found to be a
      primary target population of TPO. Quantitative measurement of hTPO-induced
      proplatelet formation was performed in liquid cultures. Proplatelet formation
      from megakaryocytes derived from GpIIb/IIIa+ CFU-MK in the presence of hTPO began
      on day 4 of culture and peaked the following day. On day 5 of culture, lower
      concentrations of hTPO expanded the number of megakaryocytes, increased the
      number of proplatelets and the percentage of proplatelet-developing
      megakaryocytes. Increasing hTPO concentrations resulted in a modest decrease in
      proplatelet development. We next used hTPO to derive immature or mature
      megakaryocytes from GpIIb/IIIa+ CFU-MK. These populations of cultured
      megakaryocytes spontaneously formed proplatelets when recultured in the absence
      of exogenous hTPO. The addition of hTPO at higher concentrations modestly
      augmented proplatelet production from immature megakaryocytes derived from 2-day
      liquid cultures. However, either murine interleukin-6 (IL-6) or human IL-11, but
      not rat IL-3, was more potent than hTPO in augmenting proplatelet formation from
      immature megakaryocytes. Each of these four cytokines had an inhibitory effect on
      proplatelet formation from more differentiated megakaryocytes derived from 3-day
      liquid cultures. These results indicate that TPO enhances proplatelet production
      primarily by stimulating CFU-MK to increase the number of proplatelet-forming
      megakaryocytes and that its action is clearly different from those of other
      cytokines that also stimulate megakaryocytopoiesis.

PMID- 9015254
TI  - Function and morphology of the retinal pigment epithelium after light-induced
      damage.
AB  - The purpose of this study was to determine the threshold energy for light-induced
      functional damage of the retinal pigment epithelium at various wavelengths.
      Retinas of 58 pigmented and 21 albino rabbits were exposed to low intensity
      broadband blue light (400-520 nm), yellow light (510-740 nm), and narrowband blue
      light (408, 417, 439, 455, 485, 501 nm, respectively; deltalambda = 10-13 nm).
      The intensity values were 50, 280, and 5 mW x cm (-2), respectively, and the
      illumination time was 0.5 up to 5 h. The cumulative dose of light energy was
      calculated from these data (J x cm(-2)). The blood-retinal barrier dysfunction
      was evaluated in vivo using fluorophotometry to measure the leakage of
      fluorescein into the vitreous after intravenous injection and in vitro using
      light and electron microscopy after an in vivo intraarterial injection of
      horseradish peroxidase (HRP). The threshold energy for fluorescein leakage was 50
      J x cm (-2) for blue light and 1,600 J x cm(-2) for yellow light. After broadband
      blue light exposure, the HRP reaction product was seen in the cytoplasm of the
      retinal pigment epithelium (RPE) cells and in the subretinal space but only if
      fluorescein leakage had been observed. Threshold energy and fluorescein leakage
      as a function of light energy were similar for albino and pigmented rabbits (P >
      0.5). Only after yellow light exposure in excess of 3,700 J x cm(-2) was
      fluorescein leakage found. In that case complete disruption of the RPE was seen,
      but no HRP was observed in the RPE cytoplasm. Of the narrow-band blue light
      exposures, only that at lambda = 418 nm caused a significant increase in
      fluorescein leakage; the threshold energy was 18 J x cm(- 2). Blue light was
      found to be at least 30 times more efficient than yellow light in causing
      dysfunction of the blood-retinal barrier. The most efficient wavelength was 418
      nm, corresponding with the absorption spectrum of cytochrome c oxidase. Melanin
      seemed to play no role. The presence or absence of melanin in the RPE appeared to
      have no influence on the threshold energy.

PMID- 9015255
TI  - Effect of body temperature on retinal damage by 488 nm light in rat.
AB  - Retinal light damage is influenced by the body temperature during exposure, but
      previous studies do not agree on the magnitude of the effect. A study in rats
      with broadband green light reported a much larger effect than a study with 380 nm
      light. The present study set out to clarify whether the spectral composition of
      the damaging light is responsible for this discrepancy by using 488 nm instead of
      380 nm light. Wavelengths in the range of 470-550 nm are known to produce a
      different damage type than 380 nm. Small patches of retina of anesthetized rats
      were exposed to 488 nm radiation of an argon ion laser. Body temperature was
      varied between 30 and 40.5 degrees C. Three days after irradiation, the retina
      was inspected by funduscopy and prepared for light microscopy. The dose of
      radiation needed for a just visible change in fundo decreased by 6% per degree
      increase in body temperature. Damage was mainly found in the retinal pigment
      epithelium. Temperature had no effect on damage morphology. The temperature
      effect at 488 nm is much smaller than reported for broadband green light. We
      conclude that the spectral composition of the damaging light is not responsible
      for the discrepancy on the magnitude of the temperature effect. Other differences
      between the studies must be responsible, such as difference in retinal irradiance
      levels.

PMID- 9015256
TI  - Synaptic growth in the rod terminals of mice after partial photoreceptor cell
      loss: a three-dimensional ultrastructural study.
AB  - Following partial loss of photoreceptor cells in the retina of mice afflicted by
      mutant genes, damaging light exposure, or old age, some of the remaining rod
      cells exhibited a process of growth in their synapses with the second order
      retinal neurons. This growth was recognized by the presence of multiple synaptic
      sites in some of the rod terminals in the outer plexiform layer. In this study, a
      comparative analysis of the microanatomical changes in the synaptic structures of
      the rod terminals in the retina of normal, rds homozygous and heterozygous mutant
      and light exposed albino mice was undertaken by using a computer-aided three
      dimensional reconstruction. A rod terminal normally showed the presence of 1
      synaptic complex consisting of a single synaptic ribbon located between 2
      processes of horizontal cells and 2 bipolar cell dendrites. In a rod terminal
      showing an enlarged synaptic complex, 2 or 3 separate synaptic ribbons formed the
      centres of separate synaptic sites; each of the sites was characterized by the
      presence of 2 laterally placed horizontal cell processes and 2 bipolar cell
      dendrites. However, these processes from the multiple synaptic sites were
      observed to arise from the 2 horizontal and the 2 bipolar cell elements that were
      normally present in the rod terminal. Thus proliferation of synaptic sites in the
      rod terminals occurred through growth and sprouting from the processes of the
      second order neuronal components present within the terminals. The altered
      synaptic complexes in the variously affected groups were structurally comparable
      and appeared to have resulted from similar microanatomical changes. The increase
      in the frequency of rod terminals with multiple synaptic sites occurred as a
      sequel to increasing photoreceptor cell loss that was recorded at different age
      points in the different experimental groups. It is concluded that rod synapses in
      the adult mammalian retina possess structural plasticity that permits
      compensatory growth.

PMID- 9015257
TI  - Morphologic changes in age-related maculopathy.
AB  - Age-related maculopathy (ARM) is a degenerative disorder of the central part of
      the retina with a rising prevalence in patients 50 years of age and older, and
      comprises different histopathological changes. The morphologic changes in ARM are
      described and illustrated with light-microscopical, electron microscopical, and
      fundus pictures. Furthermore, the most important biochemical data are given. The
      most prominent aging changes in early stages of ARM are drusen and basal laminar
      deposit (BLD), both extracellular deposits, that are assumed to be important in
      the development of ARM. Drusen accumulate within Bruch's membrane, whereas BLD is
      present between Bruch's membrane and the retinal pigment epithelium. Although the
      histopathologic characteristics of the deposits are well documented, the chemical
      composition has only been partly resolved. Biochemical analysis of these deposits
      is necessary to determine the source of the deposits and to find possible ways to
      avoid or treat them. The late stages of ARM, geographic atrophy, and neovascular
      (disciform) degeneration, are called age-related macular degeneration (AMD), and
      result in severe and irreversible visual impairment. Since there is still no
      adequate therapy for the majority of people disabled by AMD, and because of the
      aging population resulting in even more patients with this disease, it is
      necessary to intensify the research on ARM in order to prevent AMD or find a
      therapy for it.

PMID- 9015259
TI  - The first decade of continuous progress in retinal transplantation.
AB  - In recent months, neural fetal retina has been transplanted into blind human
      patients affected by Retinitis Pigmentosa. Initial success, as documented by
      improved visual activity, has been reported (del Cerro et al., Neuroscience
      Abstract, 1996). With the rapid progress in human patients, additional questions
      are arising concerning transplantation issues. Additional answers and further
      success in treating clinical disease will necessarily come from new laboratory
      research in animal models as well as in vitro systems. This increases the need
      for evaluation of the data already gathered over the first decade of retinal
      transplantation. The extensive experimental background work that preceded the
      current wave of human retinal transplants is reviewed in this paper, with
      particular emphasis given to the work dealing with the transplantation of neural
      retina.

PMID- 9015258
TI  - Correlation of DNA fragmentation and chromatin condensation in apoptotic nuclei
      of the Ser 6 mouse retina.
AB  - The form of cell death known as apoptosis was first described in thymocytes. The
      hallmarks of apoptosis include chromatin condensation, membrane blebbing,
      formation of apoptotic bodies, and DNA fragmentation. DNA fragmentation can be
      visualized morphologically by the TdT-mediated dUTP-biotin nick end labeling
      (TUNEL) method that labels the cut DNA ends. However, at the light microscopic
      (LM) level, TUNEL-positive nuclei cannot readily be correlated with the other
      hallmarks of apoptosis. In the retina, chromatin condensation and DNA
      fragmentation are the major features of developmental cell death as well as
      photoreceptor degeneration. We performed TUNEL at the electron microscopic (EM)
      level, which permitted correlation of DNA fragmentation with chromatin
      condensation. We studied the retinas of transgenic mice (Ser 6) expressing the
      Pro347Ser mutant rhodopsin gene during developmental cell death (age 7 days) and
      photoreceptor degeneration (age 21 days). We found that 90% of the nuclei showing
      chromatin condensation were TUNEL positive as well. Our results demonstrated DNA
      fragmentation and chromatin condensation in the same cells as they underwent
      apoptosis in vivo, confirming the notion that these processes are concomitant
      events, and by implication, that activation of an endogenous endonuclease is an
      important step in the death process of retinal neurons.

PMID- 9015260
TI  - Neuroglian is expressed on cells destined to form the prothoracic glands of
      Manduca embryos as they segregate from surrounding cells and rearrange during
      morphogenesis.
AB  - A cell surface protein (3B11) is differentially expressed in the embryonic labial
      segment of Manduca as two circular monolayers of epithelial cells invaginate and
      segregate from surrounding epithelial cells. The cells that invaginate and
      preferentially express 3B11 represent the presumptive prothoracic glands. These
      cells continue to express protein 3B11 as they rearrange to form first a three
      dimensional aggregate and later anastomosing filaments of cells. In the
      differentiated prothoracic gland, expression of 3B11 is restricted to sites of
      cell-cell contact. Cloning and sequencing of the cDNA for protein 3B11 revealed
      that this protein is the Manduca counterpart of Drosophila neuroglian and mouse
      L1. These surface proteins are known to function as adhesion/recognition
      molecules during development. Manduca neuroglian shares 58 and 31% identity
      respectively with the Drosophila and mouse proteins and has a cytoplasmic domain
      of over 100 amino acids.

PMID- 9015261
TI  - Induction of trunk lateral cells, the blood cell precursors, during ascidian
      embryogenesis.
AB  - The tadpole larvae of the ascidian Halocynthia roretzi have trunk lateral cells
      (TLCs) in their trunk. TLCs give rise to adult blood cells after metamorphosis.
      TLCs are exclusively derived from the A7.6 cell pair of 64-cell embryos. When
      prospective TLC blastomeres were isolated from embryos before the 16-cell stage,
      they failed to express TLC-specific antigen, a molecular indication of
      differentiation of TLCs. Isolates after the 32-cell stage, however, autonomously
      expressed the antigen. Results of experiments involving coisolation and
      recombination of blastomeres at the 16-cell stage showed that the inductive
      influence emanating from cells of animal hemisphere (presumptive epidermis
      blastomeres) is required for TLC formation. The inductive interaction takes place
      at the 16-cell stage, two cell cycles before the developmental fate becomes
      exclusively restricted to TLC formation. The inducing activity is distributed
      widely in animal hemisphere. By contrast, only presumptive TLC blastomeres have
      competence to be induced to form TLCs.

PMID- 9015262
TI  - Agrin inhibits neurite outgrowth but promotes attachment of embryonic motor and
      sensory neurons.
AB  - Agrin is a secreted glycoprotein with the ability to cluster cell surface
      molecules, including the nicotinic acetylcholine receptor (AchR) on muscle cells.
      Alternate splicing of agrin mRNA results in a family of agrin proteins which
      differ in their clustering potency. Neuronal-specific isoforms with the highest
      clustering activity play a role in clustering postsynaptic proteins at the
      neuromuscular junction. However, the function of agrin isoforms expressed in many
      nonneuronal tissues, and only weakly active in clustering assays, remains
      obscure. Monolayer cultures of Chinese hamster ovary (CHO) cells expressing a
      neuronal (agrin-19) or a nonneuronal (agrin-0) form of agrin were used to assay
      the effect of agrin on neurite outgrowth and cell attachment. These results were
      compared to outgrowth on control CHO cells expressing only drug resistance and on
      regions of CHO-agrin monolayers not expressing detectable levels of agrin.
      Neurite extension on confluent monolayers of agrin-0- or -19-expressing CHO cells
      was reduced substantially below that of controls. In one experiment neurite
      lengths were compared at 2 and 3 days after plating and suggested that neurite
      outgrowth may be stopped and not simply retarded. Attachment of sensory or
      motoneurons was nearly twofold higher to agrin monolayers than to control cells,
      showing that the inhibition is not a result of a nonpermissive environment. An
      agrin construct missing the C-terminal half, removing the major site of
      variability and clustering activity, was also tested. This construct did not
      reduce outgrowth, suggesting that the C-terminal half of the protein may be
      important in stopping growth as well as inducing clustering. These results expand
      the role of agrin in synaptogenesis as it may provide a stop signal at the
      myofiber surface and may anchor the presynaptic fibers to the eventual motor
      endplate .

PMID- 9015263
TI  - Genes required for GLP-1 asymmetry in the early Caenorhabditis elegans embryo.
AB  - The translation of maternal glp-1 mRNA is regulated both temporally and spatially
      in the early Caenorhabditis elegans embryo (T. C. Evans, S. L. Crittenden, V.
      Kodoyianni, and J. Kimble, Cell 77, 183-194, 1994). To investigate the control of
      embryonic glp-1 expression, we have examined the distribution of GLP-1 protein in
      selected maternal effect mutants that affect pattern or fate in the early embryo.
      We find that mutants that disrupt anterior-posterior asymmetry in the early
      embryo (par-1-par-6, emb-8, Par(q537)) disrupt the spatial but not temporal
      control of GLP-1 expression: GLP-1 is observed at the normal stage of
      embryogenesis in par-like mutants; however, it is uniformly distributed. In
      contrast, mutants that alter blastomere identity (skn-1, pie-1, mex-1, apx-1) do
      not affect the normal GLP-1 pattern. We conclude that genes controlling the
      asymmetry of cellular components, including P granules, also control GLP-1
      asymmetry in the early embryo. The finding that mutants that disrupt anterior
      posterior asymmetry translate GLP-1 in all blastomeres suggests that loss of
      embryonic asymmetry causes translational activation of GLP-1 in the posterior.

PMID- 9015264
TI  - Distinct stress-inducible and developmentally regulated heat shock transcription
      factors in Xenopus oocytes.
AB  - The presence of a maternal pool of heat shock factor (HSF) in Xenopus oocytes has
      been suggested by two lines of evidence from previous studies. First, heat shock
      response element (HSE)-binding activity is induced in heat-shocked eggs and
      embryos prior to expression of zygotic HSF. Second, expression from microinjected
      heat shock protein promoters in oocytes is induced upon heat shock. To date,
      however, endogenous oocyte HSF molecules have not been detected, nor has
      induction of HSE-binding activity been directly demonstrated. Here we report the
      detection of distinct stress-inducible and developmentally regulated HSE-binding
      activities of endogenous oocyte factors. Exposure of defolliculated oocytes to
      heat, cadmium, and arsenite resulted in the formation of an HSE-specific complex
      detectable by gel mobility shift assay. Induction of HSE-binding activity by each
      of these stressors corresponded to increased expression from a microinjected
      hsp70 promoter. The stress-inducible HSE-binding complex was recognized by
      antiserum against mammalian HSF1, but not by HSF2 antiserum, suggesting that a
      Xenopus homologue of HSF1 is the major component of this activity. The HSE
      binding activity of HSF1 was induced by stress treatments of stage I through VI
      oocytes, an indication that it is responsive to stress throughout oogenesis.
      During recovery from heat shock, the HSF1-HSE complex rapidly declined to control
      levels, but was induced for prolonged periods in oocytes exposed to continuous
      stress, a pattern unlike the transient activation previously observed in
      fertilized eggs or embryos. The kinetics of HSF1 activation in oocytes suggests
      that a key protein(s) regulating attenuation of the stress response is present at
      exceedingly low levels or is somehow modified during preembryonic development. We
      also detected an unusual constitutive HSE-binding complex in unstressed stage I
      and II oocytes, but not in later stage oocytes, eggs, developing embryos, or A6
      cells. This constitutive complex was unaffected by heat or chemical treatments
      and was not recognized by either HSF1 or HSF2 antiserum. Appearance of the
      constitutive HSE-binding activity during oogenesis corresponded closely with peak
      levels of hsp70 mRNA detected by Northern blot analysis of RNA from staged
      oocytes. We suggest that the constitutive HSE-binding activity in early oocytes
      is formed by a unique developmentally regulated heat shock factor that may play a
      role in the expression of heat shock proteins during early stages of oogenesis.

PMID- 9015265
TI  - Developmental defects in mouse embryos lacking N-cadherin.
AB  - To investigate the functions of N-cadherin in vivo, we have mutated the gene
      encoding this adhesion protein in mice. Although N-cadherin is expressed at the
      time of gastrulation and neurulation, both neurulation and somitogenesis initiate
      apparently normally in homozygous mutant embryos. However, the resulting
      structures are often malformed. The somites of the mutant embryos are small,
      irregularly shaped, and less cohesive compared with those of their wild-type
      littermates, and the epithelial organization of the somites is partially
      disrupted. Undulation of the neural tube is also observed in the mutant embryos.
      Homozygous mutant embryos die by Day 10 of gestation. The mesodermal and
      endodermal cell layers of the yolk sac are separated in the mutants. The most
      dramatic cell adhesion defect is observed in the primitive heart; although
      myocardial tissue forms initially, the myocytes subsequently dissociate and the
      heart tube fails to develop normally. In vitro studies of cardiac myocytes
      derived from N-cadherin mutant embryos show that the cells can loosely aggregate
      and beat synchronously, demonstrating that electrical coupling can occur between
      N-cadherin-deficient cardiac myocytes. These results show that N-cadherin plays a
      critical role in early heart development as well as in other morphogenetic
      processes.

PMID- 9015266
TI  - Analysis of cell movement and signalling during ring formation in an activated G
      alpha1 mutant of Dictyostelium discoideum that is defective in prestalk zone
      formation.
AB  - Mound formation in the cellular slime mould Dictyostelium results from the
      chemotactic aggregation of competent cells. Periodic cAMP signals propagate as
      multiarmed spiral waves and coordinate the movement of the cells. In the late
      aggregate stage the cells differentiate into prespore and several prestalk cell
      types. Prestalk cells sort out chemotactically to form the tip, which then
      controls all further development. The tip organises cell movement via a scroll
      wave that converts to planar waves in the prespore zone leading to rotational
      cell movement in the tip and periodic forward movement in the prespore zone.
      Expression of an activated G alpha1 protein under its own promoter leads to a
      severely altered morphogenesis from the mound stage onwards. Instead of forming a
      tipped mound, the cells form a ring-shaped structure without tip. Wave
      propagation pattern and dynamics during aggregation and mound formation in the
      mutant are indistinguishable from the parental strain AX3. However, at the time
      of tip formation the spiral waves that organise the late aggregate do not evolve
      in a scroll-organising centre in the tip but transform into a circularly closed
      (twisted) scroll ring wave. This leads to the formation of a doughnut-shaped
      aggregate. During further development, the doughnut increases in diameter and the
      twisted scroll wave converts into a train of planar waves, resulting in periodic
      rotational cell movement. Although biochemical consequences resulting from this
      mutation are still unclear, it must affect prestalk cell differentiation. The
      mutant produces the normal proportion of prespore cells but is unable to form
      functional prestalk cells, i.e., prestalk cells with an ability to sort out from
      the prespore cells and form a prestalk zone. Failure of sorting leads to an
      altered signal geometry, ring-shaped scroll waves, that then directs ring
      formation. This mutant demonstrates the importance of prestalk cell sorting for
      the stabilisation of the scroll wave that organises the tip.

PMID- 9015267
TI  - The neurite-promoting effect of laminin is mediated by different mechanisms in
      embryonic and adult regenerating mouse optic axons in vitro.
AB  - Retinal explants from embryonic or adult mice were placed on laminin or merosin
      substrates and the outgrowth of optic fibers was assayed under serum-free
      conditions. Both substrates strongly promoted outgrowth. A blocking antibody to
      the beta1/beta3 integrin subunits completely blocked laminin-dependent growth of
      embryonic optic fibers but had no detectable effect on adult fibers. Similarly, a
      blocking antibody against the main neurite-promoting region within the globular
      domain of the E8 fragment of laminin inhibited growth of embryonic fibers but had
      no effect on adult optic fibers. The beta1 integrin subunit was identified
      immunohistochemically on both embryonic and adult fibers. These findings indicate
      that adult fibers have lost the beta1 function which dominates laminin-dependent
      growth in embryonic fibers but express a receptor for laminin-dependent growth
      that is not detectable in embryonic fibers. These findings suggest that there are
      intrinsic differences between embryonic and adult optic fibers that may have
      implications for regenerative failure in the central nervous system of adult
      mammals .

PMID- 9015268
TI  - State of commitment of prospective neural plate and prospective mesoderm in late
      gastrula/early neurula stages of avian embryos.
AB  - We examined the ability of epiblast regions of known prospective fate from the
      late gastrula/early neurula stage of avian embryos to self-differentiate when
      placed heterotopically, testing their state of commitment. Three sites were
      examined: paranodal prospective neural plate ectoderm, containing cells fated to
      form a portion of the lateral wall of the neural tube at essentially all
      rostrocaudal levels of the neuraxis; prospective mesoderm from the caudolateral
      epiblast, containing cells fated to ingress through the primitive streak and to
      form lateral plate mesoderm; and prospective mesoderm from one level of the
      primitive streak, containing cells fated to continue ingressing and form paraxial
      mesoderm. Grafts from all sites exhibited plasticity. Grafts from the prospective
      neural plate ectoderm could readily substitute for regions of prospective
      mesoderm, when transplanted to either the epiblast or primitive streak,
      undergoing an epithelial-mesenchymal transition and, where appropriate,
      expressing paraxis, a gene expressed in paraxial mesoderm. Similarly, grafts
      containing prospective mesoderm from the epiblast could readily substitute for
      regions of the prospective neural plate ectoderm, undergoing convergent-extension
      movements characteristic of neuroectodermal cells and expressing appropriate
      genes such as Engrailed-2 and Hoxb-1. Grafts containing prospective mesoderm from
      the primitive streak could also incorporate into the neural plate and undergo
      convergence-extension movements of neurulation, although their principal
      contribution was to mesodermal and endodermal structures. Collectively, our
      results demonstrate that at the late gastrula/early neurula stage, germ layer
      specific properties are not irrevocably fixed for prospective ectodermal and
      mesodermal regions of the blastoderm. Moreover, the signals responsible for the
      induction of these two tissue types must still be present and available at these
      late stages.

PMID- 9015269
TI  - In vivo NGF treatment increases proliferation in the primary sympathetic ganglia
      of chick embryos.
AB  - Nerve growth factor (NGF) is considered to be a target-derived survival or
      differentiation factor for neural crest cells of the sympathoadrenal lineage.
      However, exogenous NGF was found to have a positive effect on the size of the
      primary sympathetic ganglia (PSG) of the chick embryo, well before sympathetic
      innervation of the periphery. We have determined the cellular mechanism of NGF's
      action on the PSG by quantifying both proliferation and apoptosis. The proportion
      of PSG cells in S-phase is nearly double in NGF-treated embryos compared to that
      in controls, strongly suggesting that NGF acts as a mitogenic factor. NGF reduced
      the low level of apoptosis at this stage as well. Since trkA has not been
      detected in the avian sympathetic ganglia until later in development, we suggest
      that these early effects of exogenous NGF may be mediated by the low-affinity
      neurotrophin receptor, p75, which is expressed from neural crest migration
      stages.

PMID- 9015270
TI  - A new vector for efficient generation of p10-single-late-promoter recombinant
      baculoviruses.
AB  - A new baculovirus (BacTen) was constructed in order to generate p10 recombinant
      expression vectors at high frequency. This virus is an AcMNPV derivative, with
      the polyhedrin gene deleted and thus exhibiting p10 promoter as a single strong
      late promoter. The polyhedrin coding sequence was re-inserted subsequently under
      the control of the p10 promoter, in place of the p10 coding sequence. Two
      flanking Bsu36I restriction sites were inserted together with the polyhedrin
      coding region. BacTen can, therefore, be efficiently restricted at the p10 locus
      and used in co-transfection experiments along with p10 transfer vectors carrying
      the foreign gene to be expressed. It is shown with three independent transfer
      vectors, that the proportion of recombinants in the viral progeny can be as high
      as 80% The BacTen baculovirus represents a new powerful tool for the generation
      of p10 promoter based expression vectors. in a system without the background of
      considerable production of very late proteins.

PMID- 9015271
TI  - A primer pair for amplifying part of the genome of all potyvirids by RT-PCR.
AB  - Sequence analysis was used to design a pair of degenerate oligonucleotide primers
      that amplified a 1.6-2.1 kbp fragment from the 3' end of the genome (virion
      protein gene and part of the NIb gene) of 17 species of the Potyviridae
      ('potyvirids'); 11 potyviruses, 2 bymoviruses, 2 macluraviruses, an ipomovirus
      and a rymovirus. The 'potyvirid primer 1' hybridizes to the 3' terminal poly-A
      region of the genome, and 'potyvirid primer 2' to the genomic region encoding the
      GNNSGQ-motif of the NIb protein. Database searches showed that the potyvirid 2
      primer is specific for potyvirids. Associated analyses indicated that the
      published amino acid sequence of part of the wheat streak mosaic rymovirus NIb
      protein is probably incorrect in part.

PMID- 9015272
TI  - RT-PCR detection of dsRNAs associated with La France disease of the cultivated
      mushroom Agaricus bisporus (Lange) Imbach.
AB  - A reverse transcription-polymerase chain reaction assay (RT-PCR) is described for
      the detection of double-stranded RNA (dsRNA) molecules (M1, M2, and L3)
      associated with La France disease of the cultivated mushroom Agaricus bisporus.
      RT-PCR was faster and more sensitive than current methods used to detect dsRNA,
      such as dsRNA extraction and analysis by electrophoresis. Another major advantage
      of RT-PCR was the detection of M1 dsRNA in rapidly prepared homogenates of
      sporophores and spawn, and in compost before sporophore production. The early
      detection of La France disease by RT-PCR will enable implementation of control
      measures by growers that may reduce losses in production time associated with a
      disease outbreak. Sequence analysis of dsRNA molecules in two Australian isolates
      showed that M1 was more conserved than M2 or L3 dsRNA.

PMID- 9015273
TI  - Molecular characteristics of Junin virus.
AB  - Results suggest that protein, glycerophospolipid, galactoside, and sialyl
      glycoside residues are present in Junin virus (JV), are accessible to enzymatic
      digestion, and play an important role in infection. Four major protein bands with
      molecular masses (Mr) 64 +/- 2, 56 +/- 2, 52 +/- 3 (mean +/- standard deviation,
      n = 4) and approximately 12-18 kDa were consistently detected after denaturing
      gel electrophoresis analysis of purified attenuated JV. The 52 kDa protein showed
      a diffuse tail in the 52-56 kDa range and was considered to be the JV
      glycoprotein. By Western blotting, the 64 kDa protein bound a JV neutralizing
      antibody and was considered to be the viral nucleoprotein. Additional bands
      corresponding to larger proteins (approximately 200, 96, 86, and 78 80 kDa in
      size), as well as fainter and broader bands in the 23-44 kDa region were also
      present in purified JV preparations. The relative resistance of virus infectivity
      to RNase digestion demonstrates that the genome of JV is protected from enzymatic
      attack. Analysis of purified JV virions by electrophoresis resolved the viral
      small (S) RNA and large (L) RNA species, 3636 +/- 54 bases and 7667 +/- 154 bases
      long, respectively (average length +/- range, in four determinations). The (S)
      RNA of attenuated JV appeared slightly larger than that reported for a pathogenic
      strain, ruling out a large sequence deletion as a reason for attenuation.

PMID- 9015274
TI  - Purification of rubella virus E1-E2 protein complexes by immunoaffinity
      chromatography.
AB  - A murine monoclonal antibody directed against the E1 membrane glycoprotein of
      rubella virus was immobilized on an N-hydroxysuccinimide-activated
      chromatographic support. The antibody was used to purify rubella virus E1-E2
      protein complexes from Tween-80/diethyl ether extracts of cell culture
      supernatants containing virus particles. The adsorption behaviour of
      immunosorbents with ligand densities of 2.9, 5.4 and 11.1 mg monoclonal antibody
      per millilitre of gel was investigated using batchwise conditions. Then the
      immunoaffinity purification process was optimized with regard to adsorption
      efficiency by adjusting the flow rate, the bed height and the amount of sample
      loaded onto the column. The optimized immunoaffinity purification process which
      is reproducible and relatively simple (one-step) had a yield of 73%, a
      concentration factor of 5-8 and a purification factor of about 2600. No mouse IgG
      due to ligand leakage could be detected in the immunopurified product using an
      enzyme immunoassay. High-performance size exclusion chromatography, sodium
      dodecyl sulphate polyacrylamide gel electrophoresis, immunoblotting and electron
      microscopy showed that the immunopurified product contained rosette-like
      structures formed by complexes of E1 and E2 proteins. The product retained its
      hemagglutinating activity and proved to be suitable for application in a
      fluorescent enzyme immunoassay for determination of anti-rubella IgG in human
      serum.

PMID- 9015275
TI  - Detection of Maedi-Visna virus antibodies using a single fusion transmembrane
      core p25 recombinant protein ELISA and a modified receiver-operating
      characteristic analysis to determine cut-off values.
AB  - The core p25 and transmembrane (TM) genes of Maedi-Visna virus (MVV) were cloned
      individually into the pGEX-2T expression vector. Both proteins were expressed as
      a combined fusion protein in frame with glutathione S-transferase (GST). The
      purified recombinant antigens (GST-TM and GST-TM-p25) were used to develop a MVV
      ELISA. A preliminary assessment of the diagnostic potential of the recombinant
      antigens (GST-TM and GST-TM-p25) was made by testing the antigens against 46
      seropositive and 46 seronegative sheep and comparing the results with a
      commercial p25 ELISA kit. A two-graph receiver operating characteristic (TG-ROC)
      analysis program was used to interpret the data. The GST-TM-p25 ELISA was more
      sensitive than the commercial assay which is based on the p25 antigen alone and
      more specific than the GST-TM ELISA.

PMID- 9015276
TI  - A high sensitivity RT-PCR assay for the diagnosis of grapevine viroids in field
      and tissue culture samples.
AB  - An RNA extraction procedure, modified from published methods, and a high
      sensitivity reverse transcription-polymerase chain reaction (RT-PCR) assay have
      been developed for the detection of the five viroids in grapevines. All five
      viroids have been found in the 10 different grape varieties tested so far. This
      assay, specially optimised for viroids in low copy number by careful selection of
      DNA primers, has been used in conjunction with dot blot hybridization assay for
      the study of viroids in vines regenerated by shoot apical meristem culture (SAMC)
      and fragmented shoot apex culture (FSAC). The data indicate a differential
      reduction of viroids, rather than viroid elimination, in the regenerated vines.
      Transmission of viroids via grape seeds was also observed.

PMID- 9015277
TI  - Luminometric microplate hybridization for detection of varicella-zoster virus PCR
      product from cerebrospinal fluid.
AB  - We modified and optimized a new microplate hybridization assay to detect the
      varciella-zoster virus (VZV) PCR product, and studied cerebrospinal fluid (CSF)
      samples of 287 patients with meningitis, encephalitis or other neurological
      diseases or symptoms. Specific antibodies to VZV and reference antigens were
      determined by enzyme immunoassay from serum and CSF, they were then compared with
      clinical findings and with the results obtained by VZV-PCR using different
      detection methods for VZV-specific amplified DNA. VZV DNA was found in the CSF of
      25 patients using the microplate hybridization assay and chemiluminescence
      detection for amplified DNA. All 25 CSF samples were also positive in Southern
      blotting. Among the patients, 10 had chickenpox, 4 had shingles, and 11 had no
      rash at all. The detection rate of VZV-specific DNA by microplate hybridization
      was 30% higher than that obtained by conventional agarose gel electrophoresis. In
      most patients the diagnosis was confirmed by demonstrating specific intrathecal
      antibody production to VZV but not to other viruses. These results indicate the
      presence of VZV in the central nervous system (CNS) in many patients with
      chickenpox or shingles, and even in patients without a rash. The microplate
      hybridization assay based on chemiluminescence detection improves considerably
      the detection rate of the VZV-PCR product compared to agarose gel electrophoresis
      and will add to the list of recognized VZV infections in the CNS. It is
      especially useful in cases where there is no cutaneous manifestation.

PMID- 9015278
TI  - Efficient production of JC virus in SVG cells and the use of purified viral
      antigens for analysis of specific humoral and cellular immune response.
AB  - A new in vitro system for the production of the human polyomavirus JC virus (JCV)
      was established to circumvent the need for virus growth in primary human fetal
      glial cells (PHFG). The permanent cell line SVG, transformed by an origin
      defective mutant of Simian Virus 40 (SV40) was used to grow JCV. JCV-specific RNA
      could be detected at day 5 and viral antigen at day 6 post infection (p.i.).
      Virus production peaked at day 16. Virus could be purified by differential
      centrifugation. The purified fraction consisted mainly of mature particles but
      contained also pentamers of the major structural virus protein 1 (VP1). The VP1
      pentamers could be purified to near homogeneity. The purified virus particles
      stimulated a specific T-cell proliferation of peripheral blood monocytes (PBMCs)
      of a patient with progressive multifocal leukoencephalopathy (PML) and of two
      healthy individuals. In addition, JCV-particles and VP1-pentamers reacted
      specifically in an ELISA with a series of five PML-patient sera and four sera of
      individuals not affected by PML. These results demonstrate that purified whole
      virus particles are suitable for the analysis of specific cellular and humoral
      immune responses to JCV.

PMID- 9015279
TI  - Detection of IgG antibody to Epstein-Barr virus viral capsid antigen in saliva by
      antibody capture radioimmunoassay.
AB  - A 'G' antibody capture radioimmunoassay (GACRIA) to detect IgG to Epstein-Barr
      virus (EBV) viral capsid antigen (VCA) in saliva is described. The monoclonal
      antibody to EBV VCA used in the GACRIA bound non-specifically when testing saliva
      samples having a total IgG content of less than 2.0 mg/l, so giving false
      positive results. This problem was overcome by including 0.5% EBV-negative human
      serum in the monoclonal antibody diluent. The performance of the assay was then
      evaluated by comparing the GACRIA test on serum and saliva samples to indirect
      immunofluorescence assay (IFA) results on sera using a panel of paired
      serum/saliva samples. Compared to the corresponding serum IFA the saliva GACRIA
      had a sensitivity and specificity of 93.5 and 100%, respectively. Although less
      sensitive than IFA on serum samples, the saliva GACRIA is sufficiently sensitive
      to be used for epidemiological screening and will enable testing for anti-EBV VCA
      to be carried out easily and on a wide scale.

PMID- 9015280
TI  - Quantification of replication of clinical cytomegalovirus isolates in cultured
      endothelial cells and fibroblasts by a focus expansion assay.
AB  - A method for quantitative analysis of the growth properties of human
      cytomegalovirus (HCMV) in various cell culture systems was developed. Recent HCMV
      isolates are, in most cases cell associated, causing only limited cytopathic
      effect. This renders comparative analysis of the biological properties of such
      isolates difficult. The focus expansion assay described in this study is based on
      cocultivation of infected fibroblasts with a cell type of choice, relying on cell
      mediated infectivity. The extent of replication of a given isolate in cell
      culture is quantified by determining the size of resulting infectious foci.
      Analysis of various clinical isolates and laboratory strains indicated that this
      assay is a reliable and valid method to define growth properties of HCMV in cell
      culture. Remarkable differences in the cytopathogenicity of these isolates in
      fibroblasts as well as in endothelial cells were found. The assay will be useful
      in studies regarding cell tropism and virulence of recent HCMV isolates and for
      the quick and easy phenotypic characterization of HCMV deletion mutants.

PMID- 9015281
TI  - Application of the polymerase chain reaction for the diagnosis of fowl poxvirus
      infection.
AB  - The polymerase chain reaction (PCR) was used to amplify a 578-bp fragment of the
      fowl poxvirus (FPV) genome and with a set of primers framed a region within the
      gene coding for 4b core protein. An amplified product was detected with six
      strains of FPV, whereas none was obtained from uninfected cell cultures, skin
      tissue or four unrelated avian pathogens. The sensitivity of PCR was tested with
      nucleic acids from the FPV-infected cell cultures. The detection limit was 10(-1)
      TCID50 in an ethidium bromide-stained gel. In addition, this assay system was
      used to detect FPV in tissue specimens of skin and respiratory swabs collected
      from commercially reared chickens. The identity of the amplification products
      from the tissue specimen preparations was determined further by using a simple,
      rapid procedure in which an internally nested, end-labeled probe was used.

PMID- 9015282
TI  - V3 loop core region serotyping of HIV-1 infected patients using the FHV epitope
      presenting system.
AB  - We have reported recently a new epitope presenting system based on the Flock
      House Virus (FHV) capsid protein. The HIV-1 V3 loop core sequence IGPGRAF was
      inserted in different sites of this carrier molecule. Immunoreactivity
      experiments and molecular modelling consistently showed that the most reactive
      recombinant protein displayed the IGPGRAF sequence in a conformation which is
      most similar to that of a V3 loop reference structure. The same insertion site
      was then used to display the V3 loop apex sequences of six different HIV-1
      isolates. Sera from 32 HIV-1 infected patients were examined for their reactivity
      to our chimeric proteins and the results were compared with those obtained using
      synthetic V3 loop peptides. The data obtained were confirmed by nested PCR
      amplification and direct sequencing of the patient's V3 loops. The results showed
      that the V3 loop serotyping using the FHV hybrid proteins, was more specific than
      that obtained using synthetic peptides. This system will therefore be a useful
      tool for the correct evaluation of the immune response against different V3 loop
      core sequences.

PMID- 9015283
TI  - Improved production of recombinant AAV by transient transfection of NB324K cells
      using electroporation.
AB  - Adeno-associated virus (AAV) is useful as an integrating vector for gene
      transfer. AAV recombinants are generally produced by transient co-transfection
      methods since it has proven difficult to generate stable packaging cell lines.
      Acceptable titers of transducing recombinants should be obtainable by optimizing
      conditions for transient co-transfection. Here, using a luciferase reporter
      derivative of the AAV infectious plasmid psub201, we show that substantially
      higher yields of transducing virus can be obtained using electroporation, rather
      than calcium phosphate transfection. Furthermore, we observed that
      electroporation of NB324K cells (an SV40-transformed human cell line) with the
      helper plasmid, pAAV/Ad, with concomitant adenovirus dl309 infection, gave yields
      of luciferase transducing recombinant AAV equal or superior to those obtained
      from the more commonly employed 293 cells. NB324K cells are easier to manipulate
      and show increased cell-association of the recombinant virus (facilitating its
      concentration and purification). We also adapted an in situ infected cell
      hybridization procedure, using a digoxigenin labeled probe, as a general method
      for determining infectious titer. Titers thus estimated were similar for
      luciferase-transducing and for alkaline phosphatase-transducing AAV vectors: the
      estimated titer of the latter agreed with that determined by in situ expression
      of alkaline phosphatase. We also describe a multiple cloning site derivative of
      psub201 which should facilitate generation of further AAV recombinants.

PMID- 9015284
TI  - Detection of human immunodeficiency virus type 1 and type 2 antibodies by a new
      automated microparticle immunoassay AxSYM HIV-1/HIV-2.
AB  - A new automated microparticle enzyme immunoassay (MEIA) for the AxSYM instrument
      developed recently by Abbott Laboratories was compared with two established
      assays, i.e. HIV-1/HIV-2 3rd Gen. Plus EIA (Abbott, Delkenheim, FRG) and
      Wellcozyme HIV 1 + 2 (Murex Diagnostics, Dartford, England) devised for the
      detection of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies. A
      total of 7293 serum samples were tested by the AxSYM HIV-1/HIV-2. The test panel
      included seroconversions (n = 22), samples from HIV-1 and HIV-2 positive
      individuals, hospitalized patients, blood donors, high risk individuals. To
      challenge further the specificity of the assays, large numbers of EIA repeatedly
      reactive but Western blot negative samples, potentially cross-reactive sera,
      Western blot indeterminate specimens and samples from pregnant women were tested.
      In four seroconversion panels, HIV-1 infection was detected one bleed earlier
      with the AxSYM HIV-1/HIV-2 than with the Abbott HIV-1/HIV-2 3rd Gen. Plus EIA.
      Although the AxSYM HIV-1/HIV-2 was tested with a higher number of challenging
      sera than the alternative assays, the specificity was very high (99.4%). The
      highest number of false positive results was obtained with serum samples that
      were repeatedly reactive in EIAs different from those compared in the present
      study. The automated AxSYM system permits the testing of a large sample number in
      a rapid turn-around time and by random access urgent tests can be carried out
      even when an assay is in progress.

PMID- 9015285
TI  - A method to remove environmental inhibitors prior to the detection of waterborne
      enteric viruses by reverse transcription-polymerase chain reaction.
AB  - A method was developed to remove environmental inhibitors from sample
      concentrates prior to detection of human enteric viruses using the reverse
      transcription-polymerase chain reaction (RT-PCR). Environmental inhibitors,
      concentrated along with viruses during water sample processing, are removed by
      the method through a series of steps that includes dialysis, solvent extraction,
      ultrafiltration and glass purification. The method was tested by spiking sodium
      phosphate with poliovirus type 1 with or without humic or fulvic acids and then
      measuring virus recovery by plaque assay and RT-PCR. Results of the study
      indicated that (i) 90% of the spiked virus could be recovered from samples at the
      end of the ultrafiltration step, (ii) virus was detected in the final eluate of
      samples containing as much as 0.5 mg of humic acid or 5.0 mg of fulvic acid, and
      (iii) as little as 0.06 plaque forming units (PFU) was detectable per RT-PCR
      reaction. These results indicate that the described purification method along
      with RT-PCR is a feasible approach for detecting waterborne human enteric viruses
      in the presence of interfering substances.

PMID- 9015286
TI  - A sensitive method for the detection of murine C-type retroviruses.
AB  - A RT-PCR assay was developed for group-specific detection of murine C-type
      retroviruses using a nested set of degenerated primers. To distinguish exogenous
      viruses from related, but silent endogenous viruses, a DNAse I pretreatment of
      supernatants is applied. This is followed by a heat inactivation/denaturation
      step. The PCR method is ultrasensitive. which enables the detection of 100
      attogram of MoMuLV proviral DNA or up to 1-10 infectious mouse C-type
      retroviruses in 10 microl supernatant of infected cells. The high specificity of
      the method allows the differentiation between mouse C-type retroviruses and
      related retroviruses of the A, B, and D type and C-type retroviruses found in
      other species. It serves as a valuable tool for the screening of animal cell
      cultures for contaminations with mouse retroviruses, e.g. hybridomas or
      recombinant cell lines producing foreign proteins.

PMID- 9015287
TI  - Interaction of kunjin virus with octyl-D-glucoside extracted Vero cell plasma
      membrane.
AB  - Initial experiments using whole cells have shown that there were specific and
      saturable interactions between kunjin (KUN) virus and receptor molecules on the
      Vero cell surfaces. Solubilisation of Vero cell plasma membranes with octyl-D
      glucoside (OG) yielded an extract which also interacted specifically with KUN
      virus. This was proven using electron microscopy. When the virus-OG-extract
      complex was exposed onto Vero cell monolayers, no KUN virus was observed to enter
      into the whole cells. This would imply that there was virus-receptor interaction
      with the OG-extract leaving no free virus to attach to the whole cells. The
      attachment kinetics of KUN virus was studied further using the Scatchard analysis
      which indicated the involvement of more than one interactive macromolecule in the
      attachment event.

PMID- 9015288
TI  - Development of tests for antibodies against foot-and-mouth disease virus in
      cattle milk.
AB  - The liquid-phase blocking ELISA (LPBE) and a specific isotype assay (SIA) for
      bovine IgG1 were modified to detect antibodies against FMDV isolate O1 Manisa in
      cattle milk. Samples from vaccinated animals were mostly indistinguishable from
      negative control cattle in the LPBE but 90% of milks from convalescent animals
      (which had also been vaccinated several times previously) gave positive results.
      The SIA was able to detect 95% of cattle vaccinated up to 12 months previously,
      and 100% of the recovered animals examined. Both tests could, therefore, be used
      for surveillance purposes following an outbreak of FMD to identify herds of
      cattle which had been infected, but the SIA would be required to show the
      presence of vaccinated animals. Samples from convalescent cattle showed the
      highest correlation between antibody levels in milk and in sera. Agreement was
      also high among recently vaccinated animals, but declined with increasing time
      since immunisation, though there was still a strong correlation of IgG1 levels
      after 6 months.

PMID- 9015289
TI  - Comparison of the infectivity of the laboratory strain AD169 and a clinical
      isolate of human cytomegalovirus to human smooth muscle cells.
AB  - The results displayed by human cytomegalovirus (HCMV) IE/E antigen expression and
      virus release into the supernatant at various times post infection with a
      clinical isolate (C3/p5) and AD169 laboratory strain of HCMV, illustrated
      differences in the biology of these viruses on the various cell lines. While
      AD169 strain was shown to infect fibroblasts efficiently, it showed a low
      infectivity profile to smooth muscle cells, whereas C3/p5 displayed comparable
      infectivity characteristics on both cell lines. Neither virus demonstrated
      propensity for infecting endothelial cells, although passaging of the C3/p5 for
      additional 11 passages in endothelial cells provided virus capable of infecting
      endothelial cells efficiently. These results show that HCMV is capable of
      infecting smooth muscle cells which could be of relevance to the proposed role of
      HCMV in atherogenesis and provides further evidence on the adaptation of AD169 to
      fibroblasts.

PMID- 9015290
TI  - Development of a non-radioactive gene probe by PCR for detection of white spot
      syndrome virus (WSSV).
AB  - Combining primers created from the sequence information of two baculo-like
      viruses of penaeid shrimp, Baculovirus penaei (BP) and Monodon baculovirus (MBV),
      produced a 750 bp band on a 0.8% agarose gel using White Spot Syndrome Virus
      (WSSV), from Penaeus monodon, as the DNA template. The PCR fragment was ligated
      to a plasmid vector, (pGEM-T) and transformed, creating a 3.7 Kbp clone. The DNA
      insert was sequenced, and the original primer pair was located. Using restriction
      enzymes, the insert was isolated, excised and non-radioactively labeled. This
      cloned labeled fragment was tested by in situ hybridization for specificity and
      reactivity with BP, MBV and WSSV-infected shrimp tissues. The major advantage of
      this novel method of gene probe development is that no DNA sequence information
      of the targeted infectious agent needed to be known or available. In addition,
      tedious viral isolation and purification was circumvented. In this study,
      knowledge of the possible viral strain was important in limiting the PCR primer
      pairs investigated. The use of arbitrary primers designed for PCR assays from two
      other possibly related shrimp viruses, increased the likelihood that a generated
      PCR product would be specific for WSSV.

PMID- 9015291
TI  - Amplification, cloning and sequencing of the sigmaC-encoded gene of avian
      reovirus.
AB  - The sigmaC-encoding cDNA of avian reovirus (ARV) 1733 strain was amplified,
      cloned and sequenced using double nested polymerase chain reaction (PCR). The ARV
      sigmaC protein is a minor component of the outer capsid that induces type
      specific neutralization antibodies. Four overlapping sigmaC-encoding cDNA
      fragments were obtained. Together, the four fragments represented the whole
      coding sequence. The nucleotide and deduced amino acid sequences of sigmaC
      encoded gene of U.S. (S1133 and 1733) and Australian isolates (RAM-1 and SOM-4)
      were compared. The U.S. isolates were closely related, but different from
      Australian isolates. The degree of differences between the U.S. and Australian
      isolates was over 44.89% at both the nucleotide and deduced amino acid levels and
      suggested that the virus is evolving separately in different continents. The
      deduced amino acid sequences of ARV sigmaC indicated a heptapeptide repeat in the
      N-terminal region of ARV sigmaC existed in all ARVs. The results suggested that
      ARV sigmaC is structurally related to mammalian reovirus (MRV) sigma1.

PMID- 9015292
TI  - Detection and identification of multiple baculoviruses using the polymerase chain
      reaction (PCR) and restriction endonuclease analysis.
AB  - A technique using the polymerase chain reaction (PCR) and restriction analysis
      was developed for the simultaneous detection of eight baculoviruses. The
      baculoviruses detected by this technique were Autographa californica multiple
      embedded nuclear polyhedrosis virus (MNPV). Anticarsia gemmatalis MNPV, Bombyx
      mori MNPV, Orgyia pseudotsugata MNPV. Spodoptera frugiperda MNPV, S. exigua MNPV,
      Anagrapha falcifera MNPV, Heliothis zea single-embedded nuclear polyhedrosis
      virus (SNPV). A highly conserved DNA sequence within the coding region of the
      polyhedrin gene was targeted for amplification. One pair of degenerate primers
      was designed, and PCR conditions were optimized to produce 575 base pair
      fragments for all eight baculoviruses. Restriction analysis of the PCR products
      resulted in distinct profiles for each virus. This technique would be useful in
      monitoring the release of wild type as well as genetically engineered
      baculoviruses.

PMID- 9015293
TI  - Susceptibility of endothelial cells to bovine herpesvirus type 4 (BHV-4).
AB  - The sensitivity of two different types of cells to bovine herpesvirus type 4 (BHV
      4) was compared by median tissue culture infectious dose (TCID50) assays. The
      bovine arterial endothelial (BAE) cell culture derived from bovine carotid
      arteries was 100-1000 times more sensitive to two strains of BHV-4, Movar 33/63
      and DN 599, than Madin Darby bovine kidney (MDBK) cell line commonly used for the
      propagation of these viruses. BAE cell cultures infected with BHV-4 displayed
      cytopathic effects (CPE) earlier and more prominently than the MDBK cells
      infected with the same viruses. BAE cells were also more sensitive than MDBK
      cells in conventional plaque assays in that the former developed well
      characterized and easily recognized plaques after infection with the viruses. BAE
      cells, which are proved to be exceptionally susceptible to BHV-4, can be used in
      the detection and quantitation of BHV-4.

PMID- 9015294
TI  - Detection of porcine reproductive and respiratory syndrome virus in paraffin
      embedded tissues: comparison of immunohistochemistry and in situ hybridization.
AB  - A non-radioactive in situ hybridization (ISH) method developed recently and an
      immunohistochemical method, the immunogold silver staining (IGSS), were compared
      for the detection of porcine reproductive and respiratory syndrome virus (PRRSV)
      in formalin-fixed paraffin-embedded tissues. Serial sections from 98 tissues,
      representing different organs from PRRSV experimentally infected pigs, and serial
      sections from 46 lung tissues from field cases were tested by both methods.
      Results obtained on tissues from experimentally infected pigs and tissues from
      field cases demonstrated that ISH was more sensitive than immunohistochemistry.
      More tissues were positive by ISH compared to IGSS and also a greater number of
      labelled cells and a stronger signal in stained cells were observed in ISH
      treated sections. The ISH method described, using a 254 bp digoxigenin-labelled
      cDNA probe, is a rapid, highly specific and sensitive detection method which can
      be used for the diagnosis of PRRSV in routinely fixed and processed tissues.

PMID- 9015295
TI  - A scFv-alkaline phosphatase fusion protein which detects potato leafroll
      luteovirus in plant extracts by ELISA.
AB  - A single chain Fv antibody fragment (scFv) was obtained from a synthetic phage
      antibody library after four rounds of selection against purified preparations of
      potato leafroll luteovirus (PLRV). Nucleotide sequence analysis showed that the
      scFv belongs to the human V(H)3 family. DNA encoding the scFv was sub-cloned into
      pDAP2 such that a scFv-alkaline phosphatase fusion protein was produced by
      transformed bacteria following induction by isopropyl-beta-D
      thiogalactopyranoside (IPTG). The fusion protein was obtained at concentrations
      of 10 mg/l of Escherichia coli culture medium and these fusion protein
      preparations were used directly in ELISA to detect PLRV in sap extracts from
      infected plants. Our work is the first report of the selection of a scFv specific
      for a luteovirus from a synthetic phage-display library and the production of a
      fusion protein with alkaline phosphatase for the detection of PLRV in infected
      plants. The results demonstrate the potential of scFv and enzyme-scFv fusion
      proteins in routine testing for plant virus infection.

PMID- 9015296
TI  - Chromosome fragments possessing only one kinetochore can congress to the spindle
      equator.
AB  - We used laser microsurgery to cut between the two sister kinetochores on
      bioriented prometaphase chromosomes to produce two chromosome fragments
      containing one kinetochore (CF1K). Each of these CF1Ks then always moved toward
      the spindle pole to which their kinetochores were attached before initiating the
      poleward and away-from-the-pole oscillatory motions characteristic of
      monooriented chromosomes. CF1Ks then either: (a) remained closely associated with
      this pole until anaphase (50%), (b) moved (i.e., congressed) to the spindle
      equator (38%), where they usually (13/19 cells) remained stably positioned
      throughout the ensuing anaphase, or (c) reoriented and moved to the other pole
      (12%). Behavior of congressing CF1Ks was indistinguishable from that of
      congressing chromosomes containing two sister kinetochores. Three-dimensional
      electron microscopic tomographic reconstructions of CF1Ks stably positioned on
      the spindle equator during anaphase revealed that the single kinetochore was
      highly stretched and/or fragmented and that numerous microtubules derived from
      the opposing spindle poles terminated in its structure. These observations reveal
      that a single kinetochore is capable of simultaneously supporting the function of
      two sister kinetochores during chromosome congression and imply that vertebrate
      kinetochores consist of multiple domains whose motility states can be regulated
      independently.

PMID- 9015297
TI  - The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA
      export pathways.
AB  - The 97-kD O-linked glycoprotein, Nup98, is a component of the Xenopus laevis
      nuclear pore complex and the only vertebrate GLFG nucleoporin identified (Powers,
      M.A., C. Macauley, F. Masiarz, and D.J. Forbes. 1995. J. Cell Biol. 128:721-736).
      We have investigated possible roles of xNup98 in the nucleocytoplasmic transport
      of proteins and RNAs by analyzing the consequences of injecting monospecific
      polyclonal antibodies to xNup98 into X. laevis oocytes. We show here that nuclear
      injection of anti-xNup98 inhibited the export of multiple classes of RNAs,
      including snRNAs, 5S RNA, large ribosomal RNAs, and mRNA. In contrast, the export
      of tRNA was unaffected. Injection of anti-xNup98 into the oocyte cytoplasm had no
      effect on export of any of the RNAs. Significantly, nuclear injection of anti
      xNup98 antibodies did not inhibit import of either karyophilic proteins or
      snRNPs. This latter result is in agreement with our previous finding that Nup98
      is not an essential element of the protein import pathway. Thus, Nup98 plays a
      role specifically in RNA export from the nucleus, and it appears to be an
      essential component of multiple RNA export pathways.

PMID- 9015298
TI  - Biogenesis of the Saccharomyces cerevisiae mating pheromone a-factor.
AB  - The Saccharomyces cerevisiae mating pheromone a-factor is a prenylated and
      carboxyl methylated extracellular peptide signaling molecule. Biogenesis of the a
      factor precursor proceeds via a distinctive multistep pathway that involves COOH
      terminal modification. NH2-terminal proteolysis, and a nonclassical export
      mechanism. In this study, we examine the formation and fate of a-factor
      biosynthetic intermediates to more precisely define the events that occur during
      a-factor biogenesis. We have identified four distinct a-factor biosynthetic
      intermediates (P0, P1, P2, and M) by metabolic labeling, immunoprecipitation, and
      SDS-PAGE. We determined the biochemical composition of each by defining their NH2
      terminal amino acid and COOH-terminal modification status. Unexpectedly, we
      discovered that not one, but two NH2-terminal cleavage steps occur during the
      biogenesis of a-factor. In addition, we have shown that COOH-terminal prenylation
      is required for the NH2-terminal processing of a-factor and that all the
      prenylated a-factor intermediates (P1, P2, and M) are membrane bound, suggesting
      that many steps of a-factor biogenesis occur in association with membranes. We
      also observed that although the biogenesis of a-factor is a rapid process, it is
      inherently inefficient, perhaps reflecting the potential for regulation. Previous
      studies have identified gene products that participate in the COOH-terminal
      modification (Ram1p, Ram2p, Ste14p), NH2-terminal processing (Ste24p, Axl1p), and
      export (Ste6p) of a-factor. The intermediates defined in the present study are
      discussed in the context of these biogenesis components to formulate an overall
      model for the pathway of a-factor biogenesis.

PMID- 9015299
TI  - A novel membrane-associated metalloprotease, Ste24p, is required for the first
      step of NH2-terminal processing of the yeast a-factor precursor.
AB  - Many secreted bioactive signaling molecules, including the yeast mating
      pheromones a-factor and alpha-factor, are initially synthesized as precursors
      requiring multiple intracellular processing enzymes to generate their mature
      forms. To identify new gene products involved in the biogenesis of a-factor in
      Saccharomyces cerevisiae, we carried out a screen for MA Ta-specific, mating
      defective mutants. We have identified a new mutant, ste24, in addition to
      previously known sterile mutants. During its biogenesis in a wild-type strain,
      the a-factor precursor undergoes a series of COOH-terminal CAAX modifications,
      two sequential NH2-terminal cleavage events, and export from the cell.
      Identification of the a-factor biosynthetic intermediate that accumulates in the
      ste24 mutant revealed that STE24 is required for the first NH2-terminal
      proteolytic processing event within the a-factor precursor, which takes place
      after COOH-terminal CAAX modification is complete. The STE24 gene product
      contains multiple predicted membrane spans, a zinc metalloprotease motif (HEXXH),
      and a COOH-terminal ER retrieval signal (KKXX). The HEXXH protease motif is
      critical for STE24 activity, since STE24 fails to function when conserved
      residues within this motif are mutated. The identification of Ste24p homologues
      in a diverse group of organisms, including Escherichia coli, Schizosaccharomyces
      pombe, Haemophilus influenzae, and Homo sapiens, indicates that Ste24p has been
      highly conserved throughout evolution. Ste24p and the proteins related to it
      define a new subfamily of proteins that are likely to function as intracellular,
      membrane-associated zinc metalloproteases.

PMID- 9015300
TI  - Two separate signals act independently to localize a yeast late Golgi membrane
      protein through a combination of retrieval and retention.
AB  - The localization of proteins to late-Golgi membranes (TGN) of Saccharomyces
      cerevisiae is conferred by targeting motifs containing aromatic residues in the
      cytosolic domains of these proteins. These signals could act by directing
      retrieval from a post-Golgi compartment or by preventing exit from the TGN. To
      investigate the mechanism of localization of yeast TGN proteins, we used the
      heterologous protein A-ALP (consisting of the cytosolic domain of dipeptidyl
      aminopeptidase A [DPAP A] fused to the transmembrane and luminal domains of the
      vacuolar protein alkaline phosphatase [ALP]), which localizes to the yeast TGN.
      Insertion of the aromatic residue-based TGN localization motif (FXFXD) of DPAP A
      into the cytosolic domain of ALP results in a protein that resides in the TGN. We
      demonstrate that the FXFXD motif confers Golgi localization through retrieval
      from a post-Golgi compartment by detecting a post-Golgi processed form of this
      protein in the TGN. We present an assay that uncouples retrieval-mediated Golgi
      localization from static retention-based localization, allowing measurement of
      the rate at which proteins exit the yeast TGN. We also demonstrate that the
      cytosolic domain of DPAP A contains additional information, separate from the
      retrieval motif, that slows exit from the TGN. We propose a model for DPAP A
      localization that involves two distinct mechanisms: one in which the FXFXD motif
      directs retrieval from a post-Golgi compartment, and a second that slows the rate
      at which DPAP A exits the TGN.

PMID- 9015301
TI  - A heterodimer of thioredoxin and I(B)2 cooperates with Sec18p (NSF) to promote
      yeast vacuole inheritance.
AB  - Early in S phase, the vacuole (lysosome) of Saccharomyces cerevisiae projects a
      stream of vesicles and membranous tubules into the bud where they fuse and
      establish the daughter vacuole. This inheritance reaction can be studied in vitro
      with isolated vacuoles. Rapid and efficient homotypic fusion between salt-washed
      vacuoles requires the addition of only two purified soluble proteins, Sec18p
      (NSF) and LMA1, a novel heterodimer with a thioredoxin subunit. We now report the
      identity of the second subunit of LMA1 as I(B)2, a previously identified
      cytosolic inhibitor of vacuolar proteinase B. Both subunits are needed for
      efficient vacuole inheritance in vivo and for the LMA1 activity in cell extracts.
      Each subunit acts via a novel mechanism, as the thioredoxin subunit is not acting
      through redox chemistry and LMA1 is still needed for the fusion of vacuoles which
      do not contain proteinase B. Both Sec18p and LMA1 act at an early stage of the in
      vitro reaction. Though LMA1 does not stimulate Sec18p-mediated Sec17p release,
      LMA1 cannot fulfill its function before Sec18p. Upon Sec17p/Sec18p action,
      vacuoles become labile but are rapidly stabilized by LMA1. The action of LMA1 and
      Sec18p is thus coupled and ordered. These data establish LMA1 as a novel factor
      in trafficking of yeast vacuoles.

PMID- 9015302
TI  - Docking of yeast vacuoles is catalyzed by the Ras-like GTPase Ypt7p after
      symmetric priming by Sec18p (NSF).
AB  - Vacuole inheritance in yeast involves the formation of tubular and vesicular
      "segregation structures" which migrate into the bud and fuse there to establish
      the daughter cell vacuole. Vacuole fusion has been reconstituted in vitro and may
      be used as a model for an NSF-dependent reaction of priming, docking, and fusion.
      We have developed biochemical and microscopic assays for the docking step of in
      vitro vacuole fusion and characterized its requirements. The vacuoles must be
      primed for docking by the action of Sec17p (alpha-SNAP) and Sec18p (NSF). Priming
      is necessary for both fusion partners. It produces a labile state which requires
      rapid docking in order to lead productively to fusion. In addition to
      Sec17p/Sec18p, docking requires the activity of the Ras-like GTPase Ypt7p. Unlike
      Sec17p/Sec18p, which must act before docking, Ypt7p is directly involved in the
      docking process itself.

PMID- 9015303
TI  - Targeting of an intestinal apical endosomal protein to endosomes in nonpolarized
      cells.
AB  - Polarized cells such as epithelial cells and neurons have distinct endosomal
      compartments associated with different plasma membrane domains. The endosomes of
      the neuronal cell body and the basolateral cytoplasm of epithelial cells are
      thought to perform cellular "housekeeping" functions such as the uptake of
      nutrients and metabolites, while the endosomes in the apical cytoplasm or axons
      are thought to be specialized for the sorting and transcytosis of cell type
      specific ligands and receptors. However, it is not known if nonpolarized cells
      such as fibroblasts contain a specialized endosomal compartment analogous to the
      specialized endosomes found in neurons and epithelia. We have expressed a protein
      that is normally found in the apical early endosomes of developing intestinal
      epithelial cells in normal rat kidney fibroblasts. This apical endosomal marker,
      called endotubin, is targeted to early endosomes in transfected fibroblasts, and
      is present in peripheral as well as perinuclear endosomes. The peripheral
      endosomes that contain endotubin appear to exclude transferrin, fluid phase
      markers, and the mannose-6-phosphate receptor, although in the perinuclear region
      colocalization of endotubin and these markers is present. In addition, endotubin
      positive structures do not tubulate in response to brefeldin A and instead
      redistribute to a diffuse perinuclear location. Since this endosomal compartment
      has many of the characteristics of an apical or axonal endosomal compartment, our
      results indicate that nonpolarized cells also contain a specialized early
      endosomal compartment.

PMID- 9015304
TI  - Structure, subunit topology, and actin-binding activity of the Arp2/3 complex
      from Acanthamoeba.
AB  - The Arp2/3 complex, first isolated from Acanthamoeba castellani by affinity
      chromatography on profilin, consists of seven polypeptides; two actin-related
      proteins, Arp2 and Arp3; and five apparently novel proteins, p40, p35, p19, p18,
      and p14 (Machesky et al., 1994). The complex is homogeneous by hydrodynamic
      criteria with a Stokes' radius of 5.3 nm by gel filtration, sedimentation
      coefficient of 8.7 S, and molecular mass of 197 kD by analytical
      ultracentrifugation. The stoichiometry of the subunits is 1:1:1:1:1:1:1,
      indicating the purified complex contains one copy each of seven polypeptides. In
      electron micrographs, the complex has a bilobed or horseshoe shape with outer
      dimensions of approximately 13 x 10 nm, and mathematical models of such a shape
      and size are consistent with the measured hydrodynamic properties. Chemical cross
      linking with a battery of cross-linkers of different spacer arm lengths and
      chemical reactivities identify the following nearest neighbors within the
      complex: Arp2 and p40; Arp2 and p35; Arp3 and p35; Arp3 and either p18 or p19;
      and p19 and p14. By fluorescent antibody staining with anti-p40 and -p35, the
      complex is concentrated in the cortex of the ameba, especially in linear
      structures, possibly actin filament bundles, that lie perpendicular to the
      leading edge. Purified Arp2/3 complex binds actin filaments with a Kd of 2.3
      microM and a stoichiometry of approximately one complex molecule per actin
      monomer. In electron micrographs of negatively stained samples, Arp2/3 complex
      decorates the sides of actin filaments. EDC/NHS cross-links actin to Arp3, p35,
      and a low molecular weight subunit, p19, p18, or p14. We propose structural and
      topological models for the Arp2/3 complex and suggest that affinity for actin
      filaments accounts for the localization of complex subunits to actin-rich regions
      of Acanthamoeba.

PMID- 9015305
TI  - Identification of a mid-anaphase checkpoint in budding yeast.
AB  - Activation of a facultative, dicentric chromosome provides a unique opportunity
      to introduce a double strand DNA break into a chromosome at mitosis. Time lapse
      video enhanced-differential interference contrast analysis of the cellular
      response upon dicentric activation reveals that the majority of cells initiates
      anaphase B, characterized by pole-pole separation, and pauses in mid-anaphase for
      30-120 min with spindles spanning the neck of the bud before completing spindle
      elongation and cytokinesis. The length of the spindle at the delay point (3-4
      microm) is not dependent on the physical distance between the two centromeres,
      indicating that the arrest represents surveillance of a dicentric induced
      aberration. No mid-anaphase delay is observed in the absence of the RAD9
      checkpoint gene, which prevents cell cycle progression in the presence of damaged
      DNA. These observations reveal RAD9-dependent events well past the G2/M boundary
      and have considerable implications in understanding how chromosome integrity and
      the position and state of the mitotic spindle are monitored before cytokinesis.

PMID- 9015306
TI  - Dynamic properties of an inositol 1,4,5-trisphosphate- and thapsigargin
      insensitive calcium pool in mammalian cell lines.
AB  - The functional characteristics of a nonacidic, inositol 1,4,5-trisphosphate- and
      thapsigargin-insensitive Ca2+ pool have been characterized in mammalian cells
      derived from the rat pituitary gland (GH3, GC, and GH3B6), the adrenal tissue
      (PC12), and mast cells (RBL-1). This Ca2+ pool is released into the cytoplasm by
      the Ca2+ ionophores ionomycin or A23187 after the discharge of the inositol 1,4,5
      trisphosphate-sensitive store with an agonist coupled to phospholipase C
      activation and/or thapsigargin. The amount of Ca2+ trapped within this pool
      increased significantly after a prolonged elevation of intracellular Ca2+
      concentration elicited by activation of Ca2+ influx. This pool was affected
      neither by caffeine-ryanodine nor by mitochondrial uncouplers. Probing
      mitochondrial Ca2+ with recombinant aequorin confirmed that this pool did not
      coincide with mitochondria, whereas its homogeneous distribution across the
      cytosol, as revealed by confocal microscopy, and its insensitivity to brefeldin A
      make localization within the Golgi complex unlikely. A proton gradient as the
      driving mechanism for Ca2+ uptake was excluded since ionomycin is inefficient in
      releasing Ca2+ from acidic pools and Ca2+ accumulation/release in/from this store
      was unaffected by monensin or NH4Cl, drugs known to collapse organelle acidic pH
      gradients. Ca2+ sequestration inside this pool, thus, may occur through a low
      affinity, high-capacity Ca2+-ATPase system, which is, however, distinct from
      classical endosarcoplasmic reticulum Ca2+-ATPases. The cytological nature and
      functional role of this Ca2+ storage compartment are discussed.

PMID- 9015307
TI  - Transplantation of quail collagen-tailed acetylcholinesterase molecules onto the
      frog neuromuscular synapse.
AB  - The highly organized pattern of acetylcholinesterase (AChE) molecules attached to
      the basal lamina of the neuromuscular junction (NMJ) suggests the existence of
      specific binding sites for their precise localization. To test this hypothesis we
      immunoaffinity purified quail globular and collagen-tailed AChE forms and
      determined their ability to attach to frog NMJs which had been pretreated with
      high-salt detergent buffers. The NMJs were visualized by labeling acetylcholine
      receptors (AChRs) with TRITC-alpha-bungarotoxin and AChE by indirect
      immunofluorescence; there was excellent correspondence (>97%) between the
      distribution of frog AChRs and AChE. Binding of the exogenous quail AChE was
      determined using a species-specific monoclonal antibody. When frog neuromuscular
      junctions were incubated with the globular G4/G2 quail AChE forms, there was no
      detectable binding above background levels, whereas when similar preparations
      were incubated with the collagen-tailed A12 AChE form >80% of the frog synaptic
      sites were also immunolabeled for quail AChE attached. Binding of the A12 quail
      AChE was blocked by heparin, yet could not be removed with high salt buffer
      containing detergent once attached. Similar results were obtained using empty
      myofiber basal lamina sheaths produced by mechanical or freeze-thaw damage. These
      experiments show that specific binding sites exist for collagen-tailed AChE
      molecules on the synaptic basal lamina of the vertebrate NMJ and suggest that
      these binding sites comprise a "molecular parking lot" in which the AChE
      molecules can be released, retained, and turned over.

PMID- 9015308
TI  - NGF and neurotrophin-3 both activate TrkA on sympathetic neurons but
      differentially regulate survival and neuritogenesis.
AB  - In this report we examine the biological and molecular basis of the control of
      sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3).
      NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth
      associated genes in NGF-dependent sympathetic neurons, but it is 20-40-fold less
      efficient in supporting their survival. Both NT-3 and NGF induce similar
      sustained, long-term activation of TrkA, while NGF is 10-fold more efficient than
      NT-3 in mediating acute, short-term TrkA activity. At similar acute levels of
      TrkA activation, NT-3 still mediates neuronal survival two- to threefold less
      well than NGF. However, a mutant NT-3 that activates TrkC, but not TrkA, is
      unable to support sympathetic neuron survival or neuritogenesis, indicating that
      NT-3-mediated TrkA activation is necessary for both of these responses. On the
      basis of these data, we suggest that NGF and NT-3 differentially regulate the
      TrkA receptor both with regard to activation time course and downstream targets,
      leading to selective regulation of neuritogenesis and survival. Such differential
      responsiveness to two ligands acting through the same Trk receptor has important
      implications for neurotrophin function throughout the nervous system.

PMID- 9015309
TI  - Two peptides derived from the nerve growth factor precursor are biologically
      active.
AB  - This report provides evidence that the proregion of the NGF precursor protein
      contains two novel bioactive peptides. The presence of pairs of basic amino acid
      (aa) residues in the NGF proregion suggests that two or three peptides other than
      NGF may be generated by proteolytic cleavage. Synthetic peptides of 29 aa (LIP1)
      and 38aa (LIP2) corresponding to the sequences -71 to -43 and -40 to -3 of the
      proNGF, respectively, were used in this study. ELISA specific for these two
      peptides revealed their presence in the rat intestine. LIP1 was localized by
      immunohistochemistry in endocrine cells of the intestinal epithelium, and LIP2
      was immunoprecipitated from an intestinal extract. We also provide evidence for
      the presence of specific receptors for LIP2 in several cell lines. Scatchard
      analysis indicated the presence of a low affinity binding site with a Kd of
      approximately 10(-7) M and a high affinity binding site of 10(-9) M. Cross
      linking studies revealed receptor forms of about 140 kD and 93 kD in a prostatic
      adenocarcinoma cell line. LIP1 and LIP2 induced rapid F-actin redistribution in
      PC12 cells within 2 min of incubation, which suggests a role of LIP1 and LIP2 in
      the process of neurite outgrowth. Furthermore, both propeptides induced rapid
      tyrosine phosphorylation of the Trk protein in both prostatic adenocarcinoma
      cells and PC12 cells, thus implicating trk in their mechanism of action. These
      results support our hypothesis that two peptides within the NGF precursor protein
      are biologically active.

PMID- 9015310
TI  - A synthetic peptide corresponding to the extracellular domain of occludin
      perturbs the tight junction permeability barrier.
AB  - Occludin, the putative tight junction integral membrane protein, is an attractive
      candidate for a protein that forms the actual sealing element of the tight
      junction. To study the role of occludin in the formation of the tight junction
      seal, synthetic peptides (OCC1 and OCC2) corresponding to the two putative
      extracellular domains of occludin were assayed for their ability to alter tight
      junctions in Xenopus kidney epithelial cell line A6. Transepithelial electrical
      resistance and paracellular tracer flux measurements indicated that the second
      extracellular domain peptide (OCC2) reversibly disrupted the transepithelial
      permeability barrier at concentrations of < 5 microM. Despite the increased
      paracellular permeability, there were no changes in gross epithelial cell
      morphology as determined by scanning EM. The OCC2 peptide decreased the amount of
      occludin present at the tight junction, as assessed by indirect
      immunofluorescence, as well as decreased total cellular content of occludin, as
      assessed by Western blot analysis. Pulse-labeling and metabolic chase analysis
      suggested that this decrease in occludin level could be attributed to an increase
      in turnover of cellular occludin rather than a decrease in occludin synthesis.
      The effect on occludin was specific because other tight junction components, ZO
      1, ZO-2, cingulin, and the adherens junction protein E-cadherin, were unaltered
      by OCC2 treatment. Therefore, the peptide corresponding to the second
      extracellular domain of occludin perturbs the tight junction permeability barrier
      in a very specific manner. The correlation between a decrease in occludin levels
      and the perturbation of the tight junction permeability barrier provides evidence
      for a role of occludin in the formation of the tight junction seal.

PMID- 9015311
TI  - Adenomatous polyposis coli tumor suppressor protein has signaling activity in
      Xenopus laevis embryos resulting in the induction of an ectopic dorsoanterior
      axis.
AB  - Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are
      linked to both familial and sporadic human colon cancer. So far, a clear
      biological function for the APC gene product has not been determined. We assayed
      the activity of APC in the early Xenopus embryo, which has been established as a
      good model for the analysis of the signaling activity of the APC-associated
      protein beta-catenin. When expressed in the future ventral side of a four-cell
      embryo, full-length APC induced a secondary dorsoanterior axis and the induction
      of the homeobox gene Siamois. This is similar to the phenotype previously
      observed for ectopic beta-catenin expression. In fact, axis induction by APC
      required the availability of cytosolic beta-catenin. These results indicate that
      APC has signaling activity in the early Xenopus embryo. Signaling activity
      resides in the central domain of the protein, a part of the molecule that is
      missing in most of the truncating APC mutations in colon cancer. Signaling by APC
      in Xenopus embryos is not accompanied by detectable changes in expression levels
      of beta-catenin, indicating that it has direct positive signaling activity in
      addition to its role in beta-catenin turnover. From these results we propose a
      model in which APC acts as part of the Wnt/beta-catenin signaling pathway, either
      upstream of, or in conjunction with, beta-catenin.

PMID- 9015312
TI  - Differential regulation and function of CD73, a glycosyl-phosphatidylinositol
      linked 70-kD adhesion molecule, on lymphocytes and endothelial cells.
AB  - CD73, otherwise known as ecto-5'-nucleotidase, is a glycosyl-phosphatidylinositol
      linked 70-kD molecule expressed on different cell types, including vascular
      endothelial cells (EC) and certain subtypes of lymphocytes. There is strong
      evidence for lymphocyte CD73 having a role in several immunological phenomena
      such as lymphocyte activation, proliferation, and adhesion to endothelium, but
      the physiological role of CD73 in other cell types is less clear. To compare the
      biological characteristics of CD73 in different cell types, we have studied the
      structure, function, and surface modulation of CD73 on lymphocytes and EC. CD73
      molecules on lymphocytes are shed from the cell surface as a consequence of
      triggering with an anti-CD73 mAb, mimicking ligand binding. In contrast,
      triggering of endothelial CD73 does not have any effect on its expression.
      Lymphocyte CD73 is susceptible to phosphatidylinositol phospholipase, whereas
      only a small portion of CD73 on EC could be removed by this enzyme. Furthermore,
      CD73 on EC was unable to deliver a tyrosine phosphorylation inducing signal upon
      mAb triggering, whereas triggering of lymphocyte CD73 can induce tyrosine
      phosphorylation. Despite the functional differences, CD73 molecules on
      lymphocytes and EC were practically identical structurally, when studied at the
      protein, mRNA, and cDNA level. Thus, CD73 is an interesting example of a molecule
      which lacks structural variants but yet has a wide diversity of biological
      functions. We suggest that the ligand-induced shedding of lymphocyte CD73
      represents an important and novel means of controlling lymphocyte-EC
      interactions.

PMID- 9015313
TI  - cDNA cloning of the basement membrane chondroitin sulfate proteoglycan core
      protein, bamacan: a five domain structure including coiled-coil motifs.
AB  - Basement membranes contain several proteoglycans, and those bearing heparan
      sulfate glycosaminoglycans such as perlecan and agrin usually predominate. Most
      mammalian basement membranes also contain chondroitin sulfate, and a core
      protein, bamacan, has been partially characterized. We have now obtained cDNA
      clones encoding the entire bamacan core protein of Mr = 138 kD, which reveal a
      five domain, head-rod-tail configuration. The head and tail are potentially
      globular, while the central large rod probably forms coiled-coil structures, with
      one large central and several very short interruptions. This molecular
      architecture is novel for an extracellular matrix molecule, but it resembles that
      of a group of intracellular proteins, including some proposed to stabilize the
      mitotic chromosome scaffold. We have previously proposed a similar stabilizing
      role for bamacan in the basement membrane matrix. The protein sequence has low
      overall homology, apart from very small NH2- and COOH-terminal motifs. At the
      junctions between the distal globular domains and the coiled-coil regions lie
      glycosylation sites, with up to three N-linked oligosaccharides and probably
      three chondroitin chains. Three other Ser-Gly dipeptides are unfavorable for
      substitution. Fusion protein antibodies stained basement membranes in a pattern
      commensurate with bamacan, and they also Western blotted bamacan core protein
      from rat L2 cell cultures. The antibodies could also specifically
      immunoprecipitate an in vitro transcription/translation product from a full
      length bamacan cDNA. The unusual structure of this proteoglycan is indicative of
      specific functional roles in basement membrane physiology, commensurate with its
      distinct expression in development and changes in disease models.

PMID- 9015314
TI  - Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a
      modulator of chondrogenesis.
AB  - Retinoic acid is a signaling molecule involved in the regulation of growth and
      morphogenesis during development. There are three types of nuclear receptors for
      all-trans retinoic acid in mammals, RAR alpha, RAR beta, and RAR gamma, which
      transduce the retinoic acid signal by inducing or repressing the transcription of
      target genes (Leid, M., P. Kastner, and P. Chambon. 1992. Trends Biochem. Sci.
      17:427-433). While RAR alpha, RAR beta, and RAR gamma are expressed in distinct
      but overlapping patterns in the developing mouse limb, their exact role in limb
      development remains unclear. To better understand the role of retinoic acid
      receptors in mammalian limb development, we have ectopically expressed a modified
      RAR alpha with constitutive activity (Balkan, W., G.K. Klintworth, C.B. Bock, and
      E. Linney. 1992. Dev. Biol. 151:622-625) in the limbs of transgenic mice.
      Overexpression of the transgene was associated with marked pre- and postaxial
      limb defects, particularly in the hind limb, where expression of the transgene
      was consistently seen across the whole anteroposterior axis. The defects
      displayed in these mice recapitulate, to a large degree, many of the congenital
      limb malformations observed in the fetuses of dams administered high doses of
      retinoic acid (Kochhar, D.M. 1973. Teratology. 7:289-295). Further analysis of
      these transgenic animals showed that the defect in skeletogenesis resided at the
      level of chondrogenesis. Comparison of the expression of the transgene relative
      to that of endogenous RAR alpha revealed that downregulation of RAR alpha is
      important in allowing the chondrogenic phenotype to be expressed. These results
      demonstrate a specific function for RARalpha in limb development and the
      regulation of chondroblast differentiation.

PMID- 9015315
TI  - Abnormal compartmentalization of cartilage matrix components in mice lacking
      collagen X: implications for function.
AB  - There are conflicting views on whether collagen X is a purely structural
      molecule, or regulates bone mineralization during endochondral ossification.
      Mutations in the human collagen alpha1 (X) gene (COL10A1) in Schmid metaphyseal
      chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen alpha1 (X)
      gene (Col10a1) null mutants were previously reported to show no obvious
      phenotypic change. We have generated collagen X deficient mice, which shows that
      deficiency does have phenotypic consequences which partly resemble SMCD, such as
      abnormal trabecular bone architecture. In particular, the mutant mice develop
      coxa vara, a phenotypic change common in human SMCD. Other consequences of the
      mutation are reduction in thickness of growth plate resting zone and articular
      cartilage, altered bone content, and atypical distribution of matrix components
      within growth plate cartilage. We propose that collagen X plays a role in the
      normal distribution of matrix vesicles and proteoglycans within the growth plate
      matrix. Collagen X deficiency impacts on the supporting properties of the growth
      plate and the mineralization process, resulting in abnormal trabecular bone. This
      hypothesis would accommodate the previously conflicting views of the function of
      collagen X and of the molecular pathogenesis of SMCD.

PMID- 9015317
TI  - Evidence for expression of the 5-hydroxytryptamine-2B receptor protein in the rat
      central nervous system.
AB  - The 5-hydroxytryptamine-2B receptor is the most recent addition to the 5
      hydroxytryptamine-2 family of G-protein-coupled receptors. In the rat stomach
      fundus, 5-hydroxytryptamine-2B receptor activation causes contraction; however,
      its distribution and function in the rat CNS are unclear. By performing
      immunohistochemistry with an antiserum raised against the N-terminus of the 5
      hydroxytryptamine-2B receptor protein, this study identifies receptor expression
      in longitudinal and circular smooth muscle in the rat stomach fundus and in
      neurons in discrete nuclei in the cerebellum, lateral septum, dorsal hypothalamus
      and medial amygdala. The potential function of this receptor in the CNS is
      discussed.

PMID- 9015316
TI  - A three-dimensional collagen lattice induces protein kinase C-zeta activity: role
      in alpha2 integrin and collagenase mRNA expression.
AB  - A three-dimensional collagen lattice can provide skin fibroblasts with a cell
      culture environment that simulates normal dermis. Such a collagen matrix
      environment regulates interstitial collagenase (type I metalloproteinase [MMP-1],
      collagenase-1) and collagen receptor alpha2 subunit mRNA expression in both
      unstimulated or platelet-derived growth factor-stimulated dermal fibroblasts (Xu,
      J., and R.A.F. Clark. 1996. J. Cell Biol. 132:239-249). Here we report that the
      collagen gel can signal protein kinase C (PKC)-zeta activation in human dermal
      fibroblasts. An in vitro kinase assay demonstrated that autophosphorylation of
      PKC-zeta immunoprecipitates was markedly increased by a collagen matrix. In
      contrast, no alteration in PKC-zeta protein levels or intracellular location was
      observed. DNA binding activity of nuclear factor kappaB (NF-kappaB), a downstream
      regulatory target of PKC-zeta, was also increased by fibroblasts grown in
      collagen gel. The composition of the NF-kappaB/Rel complexes that contained p50,
      was not changed. The potential role of PKC-zeta in collagen gel-induced mRNA
      expression of collagen receptor alpha2 subunit and human fibroblast MMP-1 was
      assessed by the following evidence. Increased levels of alpha2 and MMP-1 mRNA in
      collagen gel-stimulated fibroblasts were abrogated by bisindolylmaleimide GF
      109203X and calphostin C, chemical inhibitors for PKC, but retained when cells
      were depleted of 12-myristate 13-acetate (PMA)-inducible PKC isoforms by 24 h of
      pretreatment with phorbol PMA. Antisense oligonucleotides complementary to the 5'
      end of PKC-zeta mRNA sequences significantly reduced the collagen lattice
      stimulated alpha2 and MMP-1 mRNA levels. Taken together, these data indicate that
      PKC-zeta, a PKC isoform not inducible by PMA or diacylglycerol, is a component of
      collagen matrix stimulatory pathway for alpha2 and MMP-1 mRNA expression. Thus, a
      three-dimensional collagen lattice maintains the dermal fibroblast phenotype, in
      part, through the activation of PKC-zeta.

PMID- 9015318
TI  - Gender-related differences exist in cortical [3H]nisoxetine binding and are not
      affected by prenatal morphine exposure.
AB  - The present study was designed to test the hypothesis that prenatal morphine,
      which differentially affects hypothalamic norepinephrine content and turnover in
      male and female rats, has sexually dimorphic effects on the density of
      hypothalamic norepinephrine uptake sites in adult offspring. The binding
      characteristics of norepinephrine transporters were examined in the hypothalamus,
      preoptic area and frontal cortex of adult male and female rats exposed to
      morphine (5-10 mg/kg, twice daily) or saline on gestation days 11-18. There was a
      gender-related difference in the density of norepinephrine uptake sites measured
      by [3H]nisoxetine binding in the frontal cortex of saline controls, with control
      males having significantly fewer binding sites than control females. Prenatal
      morphine administration did not reverse or eliminate this difference.
      Additionally, prenatal morphine exposure had no effects on either the binding
      capacity or the affinity of norepinephrine uptake sites in the hypothalamus,
      preoptic area or frontal cortex of adult progeny. Thus, alterations in
      hypothalamic norepinephrine content and turnover following prenatal morphine
      exposure are not reflected in alterations in norepinephrine uptake sites.
      However, recent immunocytochemical work in our laboratory correlated reductions
      in hypothalamic norepinephrine content and turnover rate with reductions in
      tyrosine hydroxylase and dopamine-beta-hydroxylase fiber density in the
      hypothalamus of morphine-exposed female rats. Therefore, the present results may
      suggest that compensatory mechanisms increase the density of norepinephrine
      uptake sites in hypothalamic terminal fields of morphine-exposed females.

PMID- 9015319
TI  - Re-evaluation of the functional anatomy of the basal ganglia in normal and
      Parkinsonian states.
AB  - In the late 1980s, a functional and anatomical model of basal ganglia
      organization was proposed in order to explain the clinical syndrome of
      Parkinson's disease. According to this model, the pathological overactivity
      observed in the subthalamic nucleus and the output station of the basal ganglia
      plays a crucial role in the pathophysiology of the motor signs of Parkinson's
      disease. The hyperactivity of subthalamic neurons in Parkinsonism is viewed as a
      direct consequence of a pathological hypoactivity of the external segment of the
      pallidum. This article reviews recent data from different experimental approaches
      that challenge the established model of basal ganglia organization by
      reinterpreting the functional interaction between the external segment of the
      pallidum and the subthalamic nucleus in both the normal and pathological state.
      Indeed, recent neurobiochemical studies have rather unexpectedly shown that the
      GABAergic and metabolic activities of the external pallidum are not decreased in
      human and non-human primates with Parkinsonism. This absence of any decrease in
      activity might be explained by the functionally antagonistic influences of the
      striatal and subthalamic afferences within the external pallidum, as suggested by
      several anatomical studies. In addition, there are clues from
      electrophysiological studies to suggest that the hyperactivity found in the
      subthalamic neurons in Parkinsonism may not depend solely on the level of
      activity in the external pallidum. In such a framework, the hyperactivity of the
      subthalamic neurons would have to be explained, at least in part, by other
      sources of excitation or disinhibition. However, any explanation for the origin
      of the subthalamic overactivity in Parkinsonism remains speculative.

PMID- 9015320
TI  - Differential effects of intrastriatal and intranigral injections of glutamate
      antagonists on motor behaviour in the reserpine-treated rat.
AB  - A variety of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid receptor antagonists, and the antiepileptic drug lamotrigine, were
      examined for their ability to restore locomotion and other behaviours when
      injected stereotaxically via indwelling cannulae into the striatum or substantia
      nigra pars reticulata of rats rendered akinetic with reserpine (5 mg/kg i.p. 24 h
      beforehand). Only the competitive N-methyl-D-aspartate antagonists 3-((+)-2
      carboxypiperazin-4-yl)-propyl-1-phosphonate and R-DL-(E)-2-amino-4-methyl-5
      phosphono-3-pentanoate stimulated locomotion from the striatum, whereas 2-amino
      phosphonopentanoic acid, the N-methyl-D-aspartate channel blockers dizocilpine
      maleate and phencyclidine, and the alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)-quinoxaline
      dione, were additionally effective in the substantia nigra pars reticulata. The N
      methyl-D-aspartate glycine site antagonist (RS)-3-amino-1-hydroxypyrrolidin-2-one
      and the glutamate release inhibitor lamotrigine failed to restore locomotion at
      these sites, and the N-methyl-D-aspartate polyamine site antagonist eliprodil was
      ineffective in the substantia nigra pars reticulata, although all compounds
      tested (except lamotrigine) induced orofacial, head and/or limb movements to some
      degree. Except for 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)-quinoxaline-dione,
      locomotion was accompanied dose-dependently by increasingly pronounced ataxia and
      postural abnormalities. These results show that the monoamine-depleted substantia
      nigra pars reticulata has a broader spectrum of responsitivity to the
      antiparkinsonian actions of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid antagonists than does the striatum, and that the
      harmful as well as the beneficial effects of these compounds on locomotion arise
      from these two structures.

PMID- 9015321
TI  - Changes of neuronal responsiveness in the mediorostral neostriatum/hyperstriatum
      after auditory filial imprinting in the domestic chick.
AB  - Auditory filial imprinting in the domestic chick is an established experimental
      model for investigating basic mechanisms of learning-related synaptic plasticity.
      In in vivo electrophysiological studies, we analysed whether imprinting alters
      the responsiveness of neurons to acoustic imprinting stimuli in the mediorostral
      neostriatum/hyperstriatum ventrale. We compared the response characteristics of
      neurons in the mediorostral neostriatum/hyperstriatum ventrale in freely behaving
      or anesthetized acoustically imprinted, non-imprinted (naive controls) and
      passive control chicks (stimulus-exposed) during presentation of either the
      imprinting stimulus or an unfamiliar discrimination stimulus. In acoustically
      imprinted chicks, the multiunit activity in anesthetized chicks and the fast
      Fourier transform power spectrum in freely behaving chicks in the mediorostral
      neostriatum/hyperstriatum ventrale were significantly changed during playback of
      the learned stimulus in comparison to spontaneous activity and compared to the
      activity during playback of the unfamiliar discrimination stimulus. In
      anesthetized non-imprinted and passive control chicks, the multiunit activity
      showed slightly enhanced activity during playback of either the imprinting or the
      discrimination stimulus in comparison to spontaneous activity. However, in both
      control groups there were no significant differences between the responses
      towards the imprinting and the discrimination stimuli. These results indicate
      that neurons in the mediorostral neostriatum/hyperstriatum ventrale change their
      responsiveness towards learned, behaviorally relevant stimuli during auditory
      filial imprinting.

PMID- 9015322
TI  - Mildly impaired water maze performance in male Fmr1 knockout mice.
AB  - Fmr1 knockout mice constitute a putative model of fragile X syndrome, the most
      common form of heritable mental disability in humans. We have compared the
      performance of transgenic mice with an Fmr1 knockout with that of normal
      littermates in hidden- and visible-platform water maze learning, and showed that
      knockouts exhibit subnormal spatial learning abilities and marginal motor
      performance deficits. During 12 training trials of the hidden-platform task,
      escape latency and path length decreased significantly in knockouts and control
      littermates, and no effect of genotype was found. During four ensuing reversal
      trials, however, significant differences were found between knockouts and control
      littermates both in escape latency and path length. During the visible-platform
      condition, the reversal trials also revealed a difference between knockouts and
      normal littermates in escape latency, but not in path length. Possibly due to
      marginal motor incapacity, knockouts swam significantly slower than controls
      during these latter trials. During both probe trials of the hidden-platform task,
      knockouts as well as normal littermates spent more time in the target quadrant
      than in the other quadrants, and percent of time spent in the target quadrant was
      the same in both groups; swimming velocity was not significantly different
      between knockouts and normal littermates during these trials. Entries in the
      target area during the probe trials did show a significant effect of genotype on
      number of entries. The present results largely confirm and extend our previous
      findings. Impaired spatial abilities in Fmr1 knockouts might have been due to
      relatively low response flexibility or high memory interference in Fmr1
      knockouts. It remains unclear, however, which brain region or neurochemical
      system might be involved in these disabilities. We conclude that Fmr1 knockout
      mice might be a valid model of fragile X mental retardation.

PMID- 9015323
TI  - Loss of Calbindin-D28K immunoreactivity from dentate granule cells in human
      temporal lobe epilepsy.
AB  - The loss of the calcium binding protein, Calbindin-D28k, from dentate granule
      cells has been observed in different animal models of epilepsy and in ischaemia.
      This decrease is accompanied by alterations of calcium and N-methyl-D-aspartate
      currents, which may explain the hyperexcitability of the dentate gyrus. In the
      present study, we found a loss of calbindin immunoreactivity from over 90% of the
      dentate granule cells in lobectomy samples from four of 10 temporal lobe epilepsy
      patients. In another four patients, over 50%, of dentate granule cells were
      devoid of calbindin immunoreactivity, whereas the remaining two cases showed a 20
      30% decrease. Electron microscopy revealed a normal ultrastructure both in
      calbindin-containing and calbindin-negative granule cells. Both calbindin
      positive and -negative mossy fibre collaterals participated in supragranular
      sprouting. As inferred from data in animal models, the lack of calbindin in
      dentate granule cells of human epileptic subjects is likely to result in
      hyperexcitability of the dentate gyrus, which may then function as a "motor" for
      seizures.

PMID- 9015324
TI  - Localization of neuronal and endothelial nitric oxide synthase isoforms in human
      hippocampus.
AB  - The aim of the study was to use immunohistochemistry to identify, in the
      hippocampal region of human brain. the distribution of neuronal and endothelial
      isoforms of the enzyme nitric oxide synthase. Numerous pyramidal neurons and
      small, presumed GABAergic interneurons throughout the pyramidal cell layer of CA1
      CA3 exhibited neuronal nitric oxide synthase-like immunoreactivity. Comparable
      immunopositive cells were seen in the granule cell and polymorphic layers of the
      dentate gyrus and in the stratum oriens. A dense plexus of immunopositive fibres
      was seen in the granule cell layer of the dentate gyrus. In contrast, endothelial
      nitric oxide synthase-like immunoreactivity was localized specifically, and with
      a pronounced punctate distribution, to the cell bodies of CA1 pyramidal neurons.
      The endothelial isoform was also present in blood vessels and in cells which
      resembled astroglia. These latter cells had a similar appearance and distribution
      to astroglia identified by their positive reaction to glial fibrillary acidic
      protein. The most frequently used method for identifying nitric oxide synthase
      containing cells in brain, the NADPH-diaphorase reaction, was also applied to
      hippocampal sections. Only occasional NADPH-diaphorase-positive cells were seen
      in the hippocampus where, in contrast to their nitric oxide synthase-like
      immunoreactivity, the pyramidal cells did not stain for NADPH-diaphorase.
      Similarly, only occasional NADPH-diaphorase-reactive varicose axons were found in
      the hippocampus in these experiments. This study is the first to identify mostly
      separate populations of cells containing neuronal and endothelial nitric oxide
      synthase isoforms in human hippocampus. The data show that NADPH-diaphorase
      histochemistry, which is frequently used to show the presence of nitric oxide
      synthase, greatly underestimates the potential for hippocampal cells to produce
      nitric oxide. The fact that human hippocampus has a great many nitric oxide
      synthase-containing cells implies that nitric oxide has a role in human
      hippocampal functions although, at the present time, these actions are not clear.
      Whether those stimuli known to produce nitric oxide, such as activation of
      glutamate N-methyl-D-aspartate receptors, cause both enzyme isoforms in CA1
      pyramidal cells to produce nitric oxide remains to be determined.

PMID- 9015325
TI  - gp120, a human immunodeficiency virus-1 coat protein, augments excitotoxic
      hippocampal injury in perinatal rats.
AB  - Recent data suggest that gp120, a human immunodeficiency virus-1 (HIV-1) coat
      glycoprotein that is secreted by HIV-infected cells, is neurotoxic, and that this
      toxicity is mediated, at least in part, by activation of N-methyl-D-aspartate
      type excitatory amino acid receptors. To test this hypothesis in vivo, we
      examined the neurotoxicity of gp120 injected intrahippocampally, alone or co
      injected with the selective excitatory amino acid agonist N-methyl-D-aspartate,
      in seven-day-old rats. Severity of injury in the lesioned hippocampus was
      assessed five days later, using three outcome measures: histopathology,
      hippocampal atrophy (derived from regional cross-sectional area measurements) and
      loss of [3H]glutamate receptor binding (based on in vitro autoradiography
      assays). To confirm that any observed effects were attributable to gp120
      bioactivity, each group of experiments included controls that received equal
      amounts of heat-treated gp120. Gp120 (200 ng) elicited minimal focal pyramidal
      cell loss immediately adjacent to the injection track; there was no hippocampal
      atrophy or loss of [3H]glutamate binding. Co-injection of 50 ng gp120 with N
      methyl-D-aspartate (5 nmol, threshold excitotoxic dose) increased the severity of
      hippocampal injury; hippocampal atrophy was greater in animals that received
      injections of 5 nmol N-methyl-D-aspartate in combination with 50 ng gp120 than in
      those that received either N-methyl-D-aspartate alone (5 nmol) or 5 nmol N-methyl
      D-aspartate+50 ng heat-treated gp120 (mean+/-S.E.M. percentage reduction in
      injected hippocampal volume vs contralateral: N-methyl-D-aspartate, -19+/-3; N
      methyl-D-aspartate+gp120, -26.8+/-2.1; N-methyl-D-aspartate+heat-treated gp120, 
      14.0+/-2.2; P<0.001, ANOVA). Treatment with the competitive N-methyl-D-aspartate
      antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (20mg/kg)
      markedly reduced the severity of injury elicited by the combination of gp120 with
      N-methyl-D-aspartate. These data support the hypothesis that locally secreted
      gp120 could exert neurotoxic effects, mediated by N-methyl-D-aspartate receptor
      activation, in vivo in the immature brain.

PMID- 9015326
TI  - Dual mode of N-methyl-D-aspartate-induced neuronal death in hippocampal slice
      cultures in relation to N-methyl-D-aspartate receptor properties.
AB  - Hippocampal slices prepared from neonatal rats were cultured for several weeks,
      and excitotoxicity induced in CA1 pyramidal neurons by N-methyl-D-aspartate was
      evaluated at different culture stages. CA1 neurons cultured for one week
      exhibited cell death predominantly within 1-3 h after a 15-min N-methyl-D
      aspartate insult (early death), whereas those cultured for three weeks showed
      cell death mainly a few hours to 24 h after the insult (delayed death). CA1
      neurons cultured for two weeks were in a transitional state, expressing only weak
      early and delayed forms of cell death in response to N-methyl-D-aspartate. The N
      methyl-D-aspartate-induced early cell death observed in the one-week group
      depended on external Cl- but did not require external Ca2+; rather, early cell
      death was enhanced in Ca2+-free solution. This early cell death was accompanied
      by cell swelling, but cell swelling alone produced by osmotic changes failed to
      induce cell death. There was no evidence that CA1 neurons in the one-week group
      were more responsive to N-methyl-D-aspartate than those in the two other groups.
      Delayed cell death examined in the three-week group depended on external Ca2+ but
      was independent of Cl-. The density of N-methyl-D-aspartate-induced whole-cell
      currents recorded from CA1 neurons in Mg2+-free solution remained unchanged
      during three weeks of culture. However, the N-methyl-D-aspartate receptor channel
      in the three-week group was more resistant to Mg2+ block than that in the one- or
      two-week group. The incidence of N-methyl-D-aspartate-induced delayed cell death
      was higher in the three-week group than in the two-week group in normal solution
      but not in Mg2+-free solution. Thus, Mg2+ block-resistant properties of the N
      methyl-D-aspartate receptor channel acquired during prolonged culture may account
      for the high incidence of N-methyl-D-aspartate-induced delayed cell death in the
      three-week group. However, the N-methyl-D-aspartate receptor subunits expressed
      in the CA1 subfield did not show any feature specific to the three-week group.
      These results show that two mechanistically distinct modes of N-methyl-D
      aspartate-induced neuronal death are manifested differentially at different
      culture stages, depending on the intrinsic neuron properties (i.e. early cell
      death) and on the properties or the responsiveness of the N-methyl-D-aspartate
      receptor (i.e. delayed cell death).

PMID- 9015327
TI  - Pilocarpine-induced seizures are accompanied by a transient elevation in the
      messenger RNA expression of the prohormone convertase PC1 in rat hippocampus:
      comparison with nerve growth factor and brain-derived neurotrophic factor
      expression.
AB  - Several prohormone convertases that are involved in the posttranslational
      processing of precursor proteins, including neuropetides, hormones and
      neurotrophic factors, are produced in the central nervous system. These include
      enzymes named furin, PC1, PC2, PC5 and PACE4. To understand better the potential
      role played by prohormone convertases in the central nervous system we studied
      the expression of their messenger RNAs in the hippocampus of rats with
      pilocarpine-induced seizures. Moreover, we compared their expression patterns
      with those of neurotrophins such as nerve growth factor and brain-derived
      neurotrophic factor, which are up-regulated in the hippocampus during seizures.
      Pilocarpine (380 mg/kg, i.p.) induced seizure activity that appeared within the
      first hour and persisted for approximately 8 h. In situ hybridization showed
      transient increases in messenger RNA for nerve growth factor and brain-derived
      neurotrophic factor that peaked at 120 min in the hippocampus. Among the
      convertases studied, only PC1 messenger RNA displayed up-regulation, with
      temporal and topographic features comparable to those of nerve growth factor and
      brain-derived neurotrophic factor messenger RNA. The expression of furin, PC2 and
      PC5 messenger RNA changed little, while PACE4 was not expressed at all, both
      before and after pilocarpine administration. The highest increase in PC1
      messenger RNA expression was found in granule cells of the dentate gyrus and, to
      a lesser extent, in the pyramidal layer of CA1 and CA3 subfields. Thus, in the
      rat hippocampus, the epileptiform activity induced by pilocarpine mediates a co
      ordinated expression of messenger RNAs for PC1, nerve growth factor and brain
      derived neurotrophic factor. Our findings suggest the involvement of PC1 in the
      processing of precursor proteins during seizure activity.

PMID- 9015328
TI  - Ketanserin selectively blocks acute stress-induced changes in NGFI-A and
      mineralocorticoid receptor gene expression in hippocampal neurons.
AB  - Serotonin and glucocorticoids interact at the hippocampus to alter neuronal
      function. Serotonin and antidepressant drugs increase glucocorticoid receptor and
      mineralocorticoid receptor gene expression in hippocampal neurons over a few
      days. The effects of serotonin are mediated via ketanserin-sensitive "serotonin-2
      type" receptors and induction of cyclic AMP, although the subsequent molecular
      mechanisms are unclear. Recently, we have shown that chronic environmental
      manipulations which induce glucocorticoid receptor gene expression in specific
      hippocampal subfields of the rat are associated with congruent induction of the
      transcription factor NGFI-A (zif268, krox24, egr-1) and repression of AP-2; both
      factors may bind to the glucocorticoid receptor gene promoter. However, any
      relationship between serotonin and these transcription factors is unknown. Here,
      we show that acute restraint stress, which causes serotonin release at the
      hippocampus, induces hipppocampal NGFI-A, but represses activator protein-2 and
      mineralocorticoid receptor gene expression within 90 min. These changes are
      sustained for 4 h, but not 12 h. Ketanserin attenuates the stress-induced rise in
      NGFI-A and fall in mineralocorticoid receptor gene expression, and partly also
      the fall in AP-2 messenger RNA expression. These data suggest that restraint
      stress, acting via serotonin release and ketanserin-sensitive serotonin
      receptors, produces rapid, transient and specific changes in transcription factor
      gene expression in hippocampal neurons. Any link between these effects and the
      control of glucocorticoid and mineralocorticoid receptor expression with chronic
      serotonin or antidepressant treatment remains to be elucidated.

PMID- 9015329
TI  - Serotonin blocks different patterns of low Mg2+-induced epileptiform activity in
      rat entorhinal cortex, but not hippocampus.
AB  - Low Mg2+-induced epileptiform activity in the entorhinal cortex is characterized
      by an initial expression of seizure-like events followed by late recurrent
      discharges. Both these forms of activity as well as the transition between them
      were blocked by serotonin. In contrast, serotonin had little effect upon the
      epileptiform activity in areas CA3 and CA1 of the hippocampus. Both forms of
      epileptiform activity in the entorhinal cortex are sensitive to N-methyl-D
      aspartate receptor antagonists and it is shown here that serotonin blocked both
      types of epileptiform activity through an effective concentration-dependent
      reduction of N-methyl-D-aspartate receptor-mediated excitatory postsynaptic
      potentials in deep layer entorhinal cortex cells. Serotonin also prolonged or
      even prevented the transition between the two types of epileptiform activity and
      we suggest that this may be through activation of the Na+/K+-ATPase. The
      resistance of epileptiform activity in CA1 and CA3 to serotonin was most likely
      related to the inability of serotonin to reduce Schaffer collateral-evoked
      excitatory postsynaptic potentials. Given the strong serotonergic inputs to both
      the hippocampus and entorhinal cortex, the differential sensitivity of the two
      regions to serotonin suggests functional differences. In addition since the late
      recurrent discharges in the entorhinal cortex are resistant to all clinically
      used anticonvulsants, serotonin may open new avenues for the development of novel
      anticonvulsant compounds.

PMID- 9015330
TI  - Protection by diphenyliodonium against glutamate neurotoxicity due to blocking of
      N-methyl-D-aspartate receptors.
AB  - The protective effect of diphenyliodonium, known as an inhibitor of flavin
      enzymes including nitric oxide synthases, was examined against the neurotoxicity
      of excitatory amino acids on cultured spinal neurons of the rat. Diphenyliodonium
      reduced the neuronal damage induced by 15-min exposure to glutamate or N-methyl-D
      aspartate in a dose-dependent manner; half effective concentrations (EC50) were
      about 3 microM for both. Protection was only observed when diphenyliodonium was
      added into the exposure medium. Diphenyliodonium showed no effect on the toxicity
      induced by 24 h exposure to non-N-methyl-D-aspartate receptor agonists. Using a
      microfluorometry technique with Fura 2, we observed that diphenyliodonium
      reversibly inhibited the N-methyl-D-aspartate-evoked intracellular Ca2+
      elevation. The amount of 45Ca2+ influx induced by N-methyl-D-aspartate was also
      inhibited by diphenyliodonium in a dose-dependent manner; EC50 was about 3
      microM. Furthermore, we examined the effect of diphenyliodonium on an opening
      activity of the N-methyl-D-aspartate receptors estimated by binding of
      dizocilpine maleate to membrane fractions from whole brain of adult rat and from
      cultured spinal neurons. Diphenyliodonium inhibited the binding of dizocilpine
      maleate dose-dependently; EC50 was 5-8 microM. These results suggest that
      diphenyliodonium is a new antagonist to the N-methyl-D-aspartate receptors and
      that diphenyliodonium protects neurons against glutamate toxicity due to a direct
      blocking of the Ca2+ influx. This conclusion is supported by the similarity of
      the stereochemical structures predicted by computer between diphenyliodonium and
      dizocilpine maleate.

PMID- 9015331
TI  - [3H]1,3-di(2-tolyl)guanidine and [3H](+)pentazocine binding sites in the rat
      brain: autoradiographic visualization of the putative sigma1 and sigma2 receptor
      subtypes.
AB  - Sigma (sigma) receptors have generated a great deal of interest on the basis of
      their possible role in psychosis and on locomotor behaviors. The effects of sigma
      drugs on these various functions are apparently mediated by different sigma
      receptor subtypes (sigma1 and sigma2). However, little information is currently
      available on the discrete anatomical distribution of these putative sigma
      receptor subtypes in the rat brain. The aim of the present study was to
      investigate, by quantitative autoradiography, the respective distribution of
      purported sigma1 and sigma2 receptor subtypes in the rat brain using [3H]1,3-di(2
      tolyl)guanidine, a universal sigma ligand, and [3H](+)pentazocine, a selective
      sigma1 ligand. Putative sigma2 receptor sites were visualized using [3H]1,3-di(2
      tolyl)guanidine in presence of a saturating concentration of (+)pentazocine.
      Specific [3H]1,3-di(tolyl)guanidine and [3H](+)pentazocine binding sites were
      found to be widely but discretely distributed in the rat brain. The highest
      densities of specific labeling were seen in various cranial nerve nuclei,
      followed by certain hippocampal sub-fields and laminae, the red nucleus, the
      interpeduncular nucleus and mid-layers of primary and secondary motor cortices.
      Lower amounts of specific binding were present in various other structures
      including most thalamic and hypothalamic nuclei, and the cerebellum.
      Interestingly, [3H]1,3-di(2-tolyl)guanidine binding in the motor cortex was found
      to be particularly resistant to a saturating concentration of (+)pentazocine
      suggesting an enrichment in the putative sigma2 receptor subtype. This also
      applies for a few other structures such as the nucleus accumbens, substantia
      nigra pars reticulata, central gray matter, occulomotor nucleus and cerebellum.
      On the other hand, the sigma1 subtype is more abundant in most other regions with
      the highest densities seen in the dentate gyrus of the hippocampal formation,
      facial nucleus, and various thalamic and hypothalamic nuclei. The comparative
      localization of the sigma1 and sigma2 receptor binding sites probably relates to
      the differential effects of sigma1 and sigma2 drugs in the rat brain.

PMID- 9015332
TI  - Quantitative analysis of mu and delta opioid receptor gene expression in rat
      brain and peripheral ganglia using competitive polymerase chain reaction.
AB  - Competitive polymerase chain reaction assays following reverse transcription have
      been developed for quantitative analysis of delta and mu opioid receptor gene
      expression. The assay was used to obtain quantitative measurements of mu and
      delta opioid receptor expression levels in different brain regions and sensory
      and sympathetic ganglia in the rat. The assays provide accurate estimates of the
      relative levels of receptor messenger RNAs by the inclusion in the assays of
      known amounts of internal standards with the same sequence, except for a small
      deletion, as the target complementary DNA. The amplification products of target
      and competitor can be distinguished by size, and their amounts measured by
      densitometry. Expression of mu and delta opioid receptor messenger RNAs in
      different regions of the rat brain, somatic and visceral sensory and sympathetic
      ganglia was investigated using this method. In the brain the highest density of
      delta receptor messenger RNA was detected in the olfactory bulb, followed by the
      striatum. The mu receptor was expressed at highest levels in the midbrain
      hypothalamic region. All the sensory ganglia studied expressed both mu and delta
      opioid receptor messenger RNAs. In the nodose ganglion we observed the highest
      level of mu receptor messenger RNA of any structure studied; in the trigeminal
      ganglion the level was about 10 times lower than that in the nodose ganglion.
      Among the dorsal root ganglia, mu receptor messenger RNA density was highest in
      the lumbar region, followed by the thoracic and cervical regions. The sympathetic
      superior cervical ganglion expressed a very low level of mu message. Delta
      receptor messenger RNA was detected only in the sensory ganglia, at levels that
      were considerably lower than in the striatum. The reverse transcription
      polymerase chain reaction assay is quantitatively reliable for comparison of
      messenger RNA levels between different RNA extracts, and sensitive enough to
      permit the detection and assay of mu and delta opioid receptor gene expression in
      a single pair of sensory or autonomic ganglia from the rat.

PMID- 9015333
TI  - GABA-like immunoreactivity in the thalamic nucleus submedius of the cat.
AB  - The distribution of GABAergic elements and their synaptic contacts in the nucleus
      submedius, a specific nociceptive relay in the medial thalamus of the cat, was
      studied using light and electron-microscopic postembedding immunohistochemical
      methods. About one-fourth of the neurons in nucleus submedius were GABA
      immunoreactive. These neurons were generally smaller than the unlabeled neurons
      and are probably local circuit neurons. Electron microscopy showed GABA
      immunoreactivity in two types of vesicle-containing profiles, F-terminals and
      presynaptic dendrites. F-terminals formed simple synapses with the dendrites of
      presumed thalamocortical relay cells. Presynaptic dendrites were involved in more
      complex synaptic arrangements that included ascending trigeminothalamic and
      spinothalamic tract terminals and thalamocortical relay cell dendrites. Analysis
      of single sections showed that about 40% of the trigeminothalamic and
      spinothalamic tract terminals, identified by anterograde transport of horseradish
      peroxidase, were presynaptic to GABAergic presynaptic dendrites. These results
      show that GABAergic neurons are frequent in nucleus submedius and that the
      GABAergic elements make synaptic connections similar to those described for other
      sensory relay nuclei, including the somatosensory ventroposterior nucleus. This
      suggests that GABAergic mechanisms play an important role in the processing of
      nociceptive and thermoreceptive information.

PMID- 9015334
TI  - Postnatal development of GABA-immunoreactive terminals in the reticular and
      ventrobasal nuclei of the rat thalamus: a light and electron microscopic study.
AB  - The postnatal development of inhibitory GABAergic circuits in the thalamic
      reticular and ventrobasal nuclei was studied in rats ranging from the day of
      birth to the end of the third postnatal week by means of a postembedding
      immunogold staining procedure to visualize GABA. In the reticular nucleus, GABA
      labeling was present from birth in cell bodies, dendrites, growth cones and a few
      synaptic terminals, whereas in the ventrobasal nucleus it was exclusively in
      axonal processes identifiable as growth cones, vesicle-rich profiles and synaptic
      terminals. In both nuclei, GABA-labeled synaptic terminals were, however, very
      scarce and immature in neonatal animals and they became numerous and
      morphologically mature only after the end of the second postnatal week. These
      findings suggest that inhibitory synaptic responses in the somatosensory thalamus
      are not yet fully mature throughout the first two postnatal weeks and support the
      hypothesis that GABA may initially play trophic roles. The relatively late
      maturation of the thalamic GABAergic system may have important functional
      consequences, as the reticulothalamic circuits are responsible for the generation
      of spindle wave oscillations whose cellular mechanisms are also involved in the
      generation of spike-and-wave (absence) seizures in humans and in animal models.

PMID- 9015335
TI  - Differential expression of estrogen receptor and neuropeptide Y by brainstem A1
      and A2 noradrenaline neurons.
AB  - The release of noradrenaline and neuropeptide Y appears to be regulated by
      estrogen in a co-ordinated fashion within specific brain regions. The present
      study has used double and triple-labelling immunocytochemical procedures to
      determine the patterns of nuclear estrogen receptor and neuropeptide Y expression
      by brainstem A1 and A2 noradrenergic neurons in the female rat. Estrogen receptor
      immunoreactive cells were detected within the ventrolateral medulla, nucleus
      tractus solitarius, area postrema and, in the very caudal medulla, the reticular
      nuclei and spinal nucleus of the trigeminal nerve. Cells double labelled for the
      estrogen receptor and dopamine-beta-hydroxylase were identified in largest
      numbers (up to seven double-labelled cells per 30-microm-thick coronal section)
      in the caudal-most medulla, where approximately 30% of A1 and 60% of A2 neurons
      were immunoreactive for the estrogen receptor. These percentages reduced in a
      linear fashion in more rostral sections and at the level of the area postrema, no
      co-expression was evident in the ventrolateral medulla and only 10% of A2 neurons
      displayed estrogen receptor immunoreactivity. Fluorescence double-labelling
      studies undertaken in colchicine-treated rats revealed that 50% and 90-100% of
      tyrosine hydroxylase-immunoreactive cells were positive for neuropeptide Y in the
      rostral ventrolateral medulla and nucleus tractus solitarius (up to 15 double
      labelled cells per section), respectively. This pattern of co-expression also
      showed a rostrocaudal bias, but in the opposite direction, such that none of the
      caudal-most A1 and only 10% of caudal A2 neurons were immunoreactive for
      neuropeptide Y. Triple-labelling experiments revealed the presence of a total of
      only three triple-labelled cells in the ventrolateral medulla and none in the
      nucleus tractus solitarius of four rats. Double-labelling studies examining
      estrogen receptor and neuropeptide Y co-expression similarly found only three
      double-labelled cells in the ventrolateral medulla. These findings provide
      immunocytochemical evidence for a clear rostrocaudal topography in nuclear
      estrogen receptor synthesis by A1 and A2 neurons and show a reverse rostrocaudal
      bias in neuropeptide Y expression by these cells. The absence of any substantial
      neuropeptide Y and estrogen receptor co-expression in A1 and A2 neurons indicates
      that these two proteins are very likely to be differentially expressed by
      brainstem noradrenergic neurons. Such observations provide further evidence for
      the biosynthetic and functional heterogeneity of brainstem noradrenergic cells
      and suggest that A1 and A2 neurons transmitting information on estrogen status
      within the brain are unlikely to utilize neuropeptide Y as a co-transmitter.

PMID- 9015336
TI  - Fast thermal waves spreading over the cerebral cortex.
AB  - Fast thermal waves spreading over the cerebral cortex were found in the white rat
      by infrared neuroimaging (thermoencephaloscopy) in the range of 3-5 microm.
      Thermal waves appeared under visual stimulation (the probability of their
      appearance = 0.92), and under background conditions (probability of appearance =
      0.42). Typically, they moved during the period from 15 s before to 25 s after
      each light flash that was presented rhythmically (1.5-3 per min). The waves
      spread over the cerebral cortex along the limited number of typical trajectories,
      which are specific for the hemisphere of their origin (ipsilateral or
      contralateral with the side of stimulation). The waves were never recorded in a
      dead animal or in a thermal standard. The amplitude of the thermal waves was in
      the range of 0.005-0.1 degrees C, with the extent of the pathway of 2-56 mm,
      length of 10-15 mm, duration of 1.2-11.4 s, and velocity of 1-33 mm/s. In about
      half of the cases the waves appeared in the contralateral visual cortex (areas 17
      and 18a), spread to the midline and crossed to the ipsilateral hemisphere (areas
      17, 18a and 7). Local waves moving along a circular trajectory and rotating
      around the central part of the contralateral area 17 were also revealed, as well
      as wave rotation around the dorsal (mainly parietal) cortical fields. Possible
      biophysical and neurophysiological mechanisms and the functional significance of
      the revealed effects are discussed.

PMID- 9015337
TI  - High-frequency gamma electroencephalogram activity in association with sleep-wake
      states and spontaneous behaviors in the rat.
AB  - The occurrence of high-frequency gamma activity (30-60 Hz) and its relationship
      to other frequency band activities were examined by spectral analysis of the
      electroencephalogram in association with sleep wake states and spontaneous
      behaviors in the rat. In the electroencephalogram, gamma wave activity was
      evident in unfiltered and high-frequency filtered recordings, in which it was
      prominent during attentive or active Wake episodes and during Paradoxical Sleep,
      when theta-like activity was also apparent. In amplitude spectra from these
      episodes, multiple peaks were evident within the gamma frequency band, indicating
      broad-band high-frequency activity, in association with a single low-frequency
      peak in the theta band. gamma peaks were attenuated during quiet Waking, in
      association with a low-frequency peak between theta and delta, and during Slow
      Wave Sleep, in association with a low-frequency peak in the delta band. In
      coherence spectra from ipsilateral cortical leads, peaks were also present within
      the gamma range and were significantly higher in Waking moving and Paradoxical
      Sleep than in Waking quiet and Slow Wave Sleep. In measures of frequency band
      amplitude, gamma activity (30.5-58.0 Hz) varied significantly across the sleep
      waking cycle, being similarly high during Wake and Paradoxical Sleep and lowest
      during Slow Wave Sleep. Across these states, gamma was negatively correlated with
      delta (1.5-4.0 Hz). In contrast, high beta (19.0-30.0 Hz) was significantly lower
      in Wake than in Slow Wave Sleep and was positively correlated with delta. gamma
      differed significantly across specific behaviors, being highest in Paradoxical
      Sleep with twitches and during Waking eating and moving behaviors, slightly lower
      in Waking attentive, lower in Waking grooming and as low in Waking quiet as
      during Slow Wave Sleep. These results indicate that the reciprocal variation of
      high-frequency gamma activity (and not beta) with low-frequency delta activity
      reflects the sleep waking cycle of the rat. Moreover, gamma activity reflects the
      degree of behavioral arousal, since it is high during active Waking, when the
      electromyogram is high, and low during quiet Waking, when the electromyogram is
      low. It also reflects cortical arousal, independent of motor activity, since it
      attains high levels in association with attentive immobility and maximal levels
      only during particular active behaviors (eating and moving and not grooming), and
      it also attains maximal levels during Paradoxical Sleep, when the nuchal
      electromyogram is minimal, but small twitches evidence dreaming. The co-variation
      of gamma and a slow oscillation in the theta band across states and behaviors
      suggests that a common system may modulate these fast and slow
      electroencephalogram rhythms, and that such modulation, potentially emanating
      from the basal forebrain, could predominate during certain states or behaviors,
      such as Paradoxical Sleep.

PMID- 9015338
TI  - Elevated basic fibroblast growth factor levels in stroke-prone spontaneously
      hypertensive rats.
AB  - Basic fibroblast growth factor is a biologically active polypeptide with
      mitogenic, angiogenic and neurotrophic properties. In the present study, the
      temporal and spatial expressions of basic fibroblast growth factor in stroke
      prone spontaneously hypertensive rats were compared to two related strains of
      rat: spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Higher
      levels of total RNA concentration were found in cerebral cortex of four-week-old
      stroke-prone rats compared to spontaneously hypertensive rats and Wistar Kyoto
      rats. Northern blot analysis showed no changes in levels of basic fibroblast
      growth factor messenger RNA with increasing age in cerebral cortex of Wistar
      Kyoto and spontaneously hypertensive rats. However, significant increases were
      found in 26- and 38-week-old stroke-prone rats compared to four-week-old stroke
      prone rats. Although messenger RNA increases were also found in subcortical and
      cerebellar regions, a significant difference in levels of basic fibroblast growth
      factor messenger RNA was observed only in cerebral cortices among these three
      strains. This age-related increase in basic fibroblast growth factor messenger
      RNA correlated with the increase incidence of stroke in stroke-prone rats.
      Immunohistochemical study further revealed a dramatic increase in levels of basic
      fibroblast growth factor immunoreactivity in cerebral cortex of 30-week-old
      stroke-prone rats as compared to young stroke-prone rats, as well as age-matched
      Wistar Kyoto and spontaneously hypertensive rats. This increase in basic
      fibroblast growth factor immunoreactivity therefore appears very specific to aged
      stroke-prone rats. However, immunoreactivity decreased once severe tissue damages
      were observed in the cerebral cortex. Basic fibroblast growth factor-positive
      cells were diffusely expressed in cerebral cortex; double staining with glial
      fibrillary acidic protein showed the majority of these basic fibroblast growth
      factor-positive cells to be astrocytes. In summary, although young stroke-prone
      spontaneously hypertensive rats showed significantly higher RNA concentration,
      significant increases in levels of basic fibroblast growth factor, including both
      messenger RNA and protein expression, were observed in aged stroke-prone rats
      with a high incidence of stroke. These findings suggest the possibility that
      basic fibroblast growth factor may play a role in the developmental sequelae of
      cerebral lesions in stroke-prone spontaneously hypertensive rats.

PMID- 9015339
TI  - Role of the flocculus in the development of vestibular compensation:
      immunohistochemical studies with retrograde tracing and flocculectomy using Fos
      expression as a marker in the rat brainstem.
AB  - After unilateral labyrinthectomy in rats, Fos-like immunoreactive neurons
      appeared in the ipsilateral medial vestibular nucleus, contralateral prepositus
      hypoglossal nucleus and contralateral inferior olive beta subnucleus. and
      thereafter gradually disappeared in accordance with the development of vestibular
      compensation. This finding indicated that the activation of these nuclei is the
      initial event of vestibular compensation. In the present study, retrograde
      tracing experiments revealed that these Fos-like immunoreactive neurons project a
      proportion of their axons to the vestibulocerebellum (uvula-nodulus, flocculus).
      Before vestibular compensation was accomplished, right, left or bilateral
      flocculectomy was performed in right-labyrinthectomized rats. All these
      treatments caused reappearance of unilateral labyrinthectomy-induced behavioral
      deficits and Fos expression in the left medial vestibular nucleus and right
      prepositus hypoglossal nucleus. Since floccular efferents are GABAergic, these
      results indicate that the neurons in which Fos expression was detected by
      flocculectomy had been inhibited after unilateral labyrinthectomy by floccular
      Purkinje neurons and that disinhibition of these neurons induced by flocculectomy
      caused decompensation. Based on our present findings, we propose a hypothesis
      that the bilateral flocculus serves the restoration of balance between
      intervestibular nuclear activities to induce vestibular compensation after
      unilateral labyrinthectomy.

PMID- 9015340
TI  - Expression of agrin in the developing and adult rat brain.
AB  - Agrin, a synaptic basal lamina protein, is essential for the formation of the
      vertebrate neuromuscular junction. Agrin's role in synaptogenesis in the central
      nervous system has, however, not been elucidated. Therefore, we performed
      immunohistochemical analysis of agrin localization in adult rat brain using agrin
      specific polyclonal antibodies. Our results show that agrin immunoreactivity is
      detected in neuronal cells throughout the brain, and that agrin is expressed in
      many morphologically and neurochemically distinct neuronal populations. Within
      neurons, agrin-immunoreactive material is present in dendrites. To determine
      agrin isoform expression in the central nervous system, we analysed the pattern
      of expression of several isoforms during development of the rat brain. Our
      results indicate that alternative splicing of agrin is specifically regulated in
      the nervous system; isoforms of the Y=4 (i.e. Ag x,4,0, Ag x,4,8 and Ag x,4,19),
      Z=8 and Z=19 type are expressed exclusively in the nervous system. Agrin
      expression precedes synaptogenesis and is developmentally regulated in neural
      tissues. To evaluate stimuli that may be involved in the regulation of agrin
      expression, we monitored the patterns of isoform expression following a
      depolarizing stimulus. Our results show that agrin expression in the adult
      hippocampus is regulated in an activity-dependent manner, with kinetics of
      induction resembling a delayed early response gene.

PMID- 9015341
TI  - Trajectory formation of the center-of-mass of the arm during reaching movements.
AB  - We attempted to identify the invariant kinematic properties of multijoint arm
      reaching movements in the horizontal plane to explore the planning variable(s)
      involved in their coordination. Different targets were placed near the perimeter
      of the workspace boundary, thereby causing variation of size and orientation of
      the hand stroke. We have a special interest in the trajectory characteristics of
      the most massive point within the arm system, the center-of-mass of the entire
      arm system, in addition to those of the hand or joints. The motion of the
      individual segments (the forearm plus hand and the upper arm) or joints (shoulder
      and elbow) was modulated in a different way depending on the tasks; thus, there
      was no invariance in the relationships between paired variables (displacement or
      velocity) for segment or joint motions. For relatively short hand strokes, the
      trajectory of the hand and the center-of-mass of the entire arm system were
      characterized by a nearly straight path, and a smooth, bell-shaped velocity curve
      along the path, symmetrical about the mid-portion of the movement, starting from
      nearly zero, growing to a single peak and declining again to nearly zero.
      However, in large hand strokes the hand path was highly curved and the velocity
      curve was asymmetric. Although the path of the center-of-mass of the entire arm
      system also tended to be curved with the increase of the hand stroke, a bell
      shaped velocity curve along the path and its typical symmetry were preserved over
      a wide range of stroke sizes and orientations, and its peak was scaled in
      proportion to movement distance and movement time. Our findings indicate that it
      is not valid to postulate solely the joint- or hand-based planning strategies
      which have been proposed previously. Rather, the planning of the spatial aspects
      of the motion is largely dependent on the interaction of multiple variables,
      including those not analysed in this study. The bell-shaped pattern of the center
      of-mass velocity profile represents a certain efficiency of movement, since it
      corresponds to a single accelerative and a decelerative phase of a mass over the
      movement, with no intermediate force reversals. The simple structure of the
      center-of-mass velocity profiles may reflect a fundamental organization principle
      underlying the temporal aspects of movement planning.

PMID- 9015342
TI  - After-effects of preceding movement on dynamic responses of spindle primary
      afferents during passive muscle lengthening in the cat.
AB  - After-effects of preceding movement on the activity of primary spindle afferents
      of de-efferented cat hindlimb muscles were examined during the dynamic phases of
      slow linear test movements. These dynamic after-effects were compared with the
      static after-effects observed in the spindle activity during steady-state of the
      parent muscle and with hysteresis after-effects of the muscle proper. According
      to their pattern, the dynamic phases of the spindle and muscle reactions can be
      divided into two parts. During the first part (at the beginning of movement),
      both spindle responses and muscle state (either length or load depending on the
      mode of the test movement) strongly depended on the previous history of movement,
      being completely independent of the direction of preceding movement in the second
      part of the dynamic phase. These two parts were treated in terms of interaction
      of the movement-dependent after-effects in muscles and muscle spindle afferents.
      These findings allowed us to suppose that, during rather slow single-joint
      movements, the spindle afferents from the passive antagonist muscles can provide
      signals free from the effects of preceding movement.

PMID- 9015343
TI  - Influence of the mucosa on the excitability of myenteric neurons.
AB  - Intracellular microelectrodes were used to examine the active and passive
      membrane properties of neurons in the myenteric plexus of the guinea-pig small
      intestine. Neurons of two types were examined: S neurons, which have prominent
      fast excitatory postsynaptic potentials and in which action potentials are not
      followed by long-lasting afterhyperpolarizations, and AH neurons, which have long
      lasting afterhyperpolarizations following soma action potentials. In preparations
      in which the myenteric ganglia and longitudinal muscle, but no mucosa, were
      present, most S neurons (59/64) responded to intracellular depolarizing current
      with brief bursts of action potentials. Regardless of the strength of a
      depolarizing current of 500-ms duration, these neurons never fired action
      potentials beyond the first 250 ms. S neurons in this state were called rapidly
      accommodating. In contrast, within 600 microm circumferential to the intact
      mucosa, 26/58 S neurons fired action potentials for most or all of the period of
      a 500-ms insightful depolarizing pulse. S neurons in this state were called
      slowly accommodating. Depolarization of S neurons in the rapidly accommodating
      state caused a rapidly developing reduction in membrane resistance (outward
      rectification; onset about 7 ms). This rectification was absent from S neurons in
      the slowly accommodating state. Tetraethylammonium blocked the early
      rectification and the changed neuronal state from rapidly accommodating to slowly
      accommodating. Application of tetrodotoxin to neurons in the slowly accommodating
      state revealed the early rectification, indicating that its absence from these
      neurons before tetrodotoxin was applied had been due to ongoing activity in axons
      providing synaptic input to the neurons. After the mucosa was disconnected from
      the other layers and laid back in its original position, all S neurons close to
      the mucosa were in the rapidly accommodating state (17/17). Slow excitatory
      postsynaptic potentials, evoked by electrical stimulation of nerve tracts,
      converted 17 of 43 S neurons from rapidly accommodating to slowly accommodating
      and eliminated the early outward rectification in these neurons. These results
      indicate that the action potential firing properties of S neurons can be changed
      by external influences, including the activity of synaptic inputs that release a
      slowly acting transmitter. Spontaneous antidromic action potentials were recorded
      in 8/62 AH neurons within 600 microm circumferential to the intact mucosa. It is
      concluded that, when the mucosa is intact, a background firing of sensory neurons
      occurs which leads to a state change in many S neurons innervated by the active
      sensory neurons. We conclude that this state change is caused by the block of a
      voltage-sensitive outward rectification.

PMID- 9015345
TI  - Involvement of cellular proteolytic machinery in apoptosis.
AB  - Programmed cell death (PCD), a genetically controlled cell deletion process,
      plays an important role in the regulation of cellular and tissue homeostasis. The
      requisite for proteolysis during PCD-induced apoptosis is well documented. The
      cellular proteolytic machinery includes numerous proteases localized in
      membranes, cytoplasm, and nucleus. This machinery may function to remove
      denatured or misfolded protein from the cytoplasm on a routine basis and may also
      cleave proteins thereby implementing their activation. The well established role
      of some proteases is to maintain fundamental cellular processes; however, the
      precise cellular location and function of other proteases which make a
      contribution to a unique unidirectional process such as apoptosis remains
      unclear. The functional overlap between 'scheduled' and 'unscheduled' proteolysis
      may potentially lead to confusion in this research area. In this review we will
      discuss certain cellular proteolytic systems and highlight the possible
      involvement of each in apoptosis.

PMID- 9015344
TI  - B-50/growth-associated protein-43, a marker of neural development in Xenopus
      laevis.
AB  - To study the regulation and function of the growth-associated protein B-50/growth
      associated protein-43 (mol. wt 43,000) in Xenopus laevis, B-50/growth-associated
      protein-43 complementary DNAs were isolated and characterized. The deduced amino
      acid sequence revealed potential functional domains of Xenopus B-50/growth
      associated protein-43 that may be involved in G-protein interaction, membrane
      binding, calmodulin-binding and protein kinase C phosphorylation. The expression
      of B-50/growth-associated protein-43 at the RNA and protein level during
      development was investigated using the Xenopus complementary DNA and the
      monoclonal B-50/growth-associated protein-43 antibody NM2. The antibody NM2
      recognized the gene product on western blot and in whole-mount
      immunocytochemistry of Xenopus embryos. Moreover, visualization of the
      developmentally regulated appearance of B-50/growth-associated protein-43
      immunoreactivity showed that this mode of detection may be used to monitor
      axonogenesis under various experimental conditions. In the adult Xenopus, XB
      50/growth-associated protein-43 messenger RNA was shown to be expressed at high
      levels in brain, spinal cord and eye using northern blotting. The earliest
      expression detected on northern blot was at developmental stage 13 with poly(A)
      RNA. By whole-mount immunofluorescence, applying the confocal laser scanning
      microscope, the protein was first detected in embryos from stage 20, where it was
      expressed in the developing trigeminal ganglion. Also later in development the
      expression of the B-50/growth-associated protein-43 gene was restricted to the
      nervous system in Xenopus, as was previously found for the mouse. In conclusion,
      we find that XB-50/growth-associated protein-43 is a good marker to study the
      development of the nervous system in Xenopus laevis.

PMID- 9015346
TI  - Inhibition of cloned human L-type cardiac calcium channels by 2,3-butanedione
      monoxime does not require PKA-dependent phosphorylation sites.
AB  - The oxime derivative 2,3-butanedione monoxime (BDM) is used as an inorganic
      phosphatase to probe the phosphorylation state of many cellular proteins
      including the L-type calcium channel in various tissues. We used BDM further to
      shed light on the controversy surrounding direct phosphorylation of the L-type
      Ca2+ channel. We employed a recombinant system that utilizes HEK 293 cells
      expressing wild type and mutant human heart calcium channels. BDM reversibly
      reduced the calcium channel current induced by expression of the wild type
      channel in a concentration-dependent manner with an apparent IC50 value of 15.3
      mM. Deletion of part of the carboxyl terminus of the alpha 1 subunit, which
      contains one putative protein kinase A site, or mutating all of the protein
      kinase A consensus sites of the pore forming subunit, did not significantly
      change the apparent IC50 value or alter in any other way the blocking effect of
      BDM on the expressed currents. Our data suggest that BDM produces reversible
      modifications of the cardiac calcium channel protein leading to an expected
      reduction in the amplitude of the expressed currents, but the site of action must
      be different from that of the consensus sites for protein kinase A dependent
      phosphorylation.

PMID- 9015347
TI  - The full length and splice variant thyrotropin receptor is expressed exclusively
      in skeletal muscle of extraocular origin: a link to the pathogenesis of Graves'
      ophthalmopathy.
AB  - Graves' ophthalmopathy occurs in up to 90% of patients with Graves' disease,
      supporting the notion of a common denominator in the development of these two
      disorders. The thyrotropin receptor has been proposed as the link for this
      clinical association. In the present study we have investigated whether
      thyrotropin receptor mRNA species exist in extraocular muscle and non-ocular
      skeletal muscle by reverse transcription-polymerase chain reaction (RT-PCR). We
      have, with high stringency RT-PCR, Southern analysis, and direct sequencing of
      PCR products, identified for the first time the presence of both full length and
      splice variant thyrotropin receptor mRNA in extraocular but not non-ocular
      skeletal muscle. This extraocular muscle thyrotropin receptor expression was
      shared, as expected, with normal thyroid but not other control tissues including
      brain and kidney. These data demonstrate that the thyrotropin receptor, the
      autoimmune target of Graves' disease, is exclusively expressed in extraocular
      muscle as well as the thyroid and lend support to the notion that it is a likely
      candidate autoantigen in Graves' ophthalmopathy.

PMID- 9015348
TI  - Application of photoaffinity labeling with [11,12-3H]all-trans-retinoic acid to
      characterization of rat liver microsomal UDP-glucuronosyltransferase(s) with
      activity toward retinoic acid.
AB  - [3H]All-trans-retinoic acid has been shown to be an effective photoaffinity label
      for microsomal UDP-glucuronosyltransferases. Labeling of rat liver microsomal
      proteins with [3H]all-trans-retinoic acid and [32P]5-azido-UDP-glucuronic acid
      has shown that at least one protein in the 50-56 kDa mass range encompassing the
      UDP-glucuronosyltransferases photoincorporated both probes. The fraction of
      solubilized microsomal protein eluted from a UDP-hexanolamine affinity column
      with 50 microM UDP-glucuronic acid contained two protein bands, both of which
      photoincorporated [3H] all-trans-retinoic acid and were detected on Western blot
      by anti-UDP-glucuronosyltransferase antibodies. Enzymatic glucuronidation
      activity toward atRA in the same fraction was enriched five-fold over that of
      native or solubilized microsomes.

PMID- 9015349
TI  - Cholinergic stimulation of human microcytoma cell line H69.
AB  - Experiments were addressed to investigate the mechanisms by which cholinergic
      stimulation is coupled to the enhancement of proliferation of small cell lung
      cancer cells H69. Muscarinic stimulation triggers the release of cytosolic Ca2+
      and of inositol(1,4,5)trisphosphate with comparable time courses. The presence of
      alpha-bungarotoxin or the absence of Ca2+ in external medium suppresses
      enhancement of clonal growth induced by brief applications of nicotine. Here we
      suggest that Ca2+ mobilization represents a trigger for the enhancement of small
      cell lung cancer cell proliferation upon cholinergic stimulation.

PMID- 9015350
TI  - Biochemical characterization of the phagocytic giant cell receptor for
      Dictyostelium discoideum amoebae: identification by cell blotting.
AB  - A critical aspect of sexual development in Dictyostelium is the selection of
      "self" as a targeted food source by the phagocytic zygotic giant cell (ZGC). It
      has previously been demonstrated that phagocytic giant cells preferentially take
      up amoebae of the same species suggesting that the process is mediated by a
      specific receptor. By using tunicamycin, which inhibits N-linked glycosylation
      and mevastatin and mevinolin, which both inhibit HMG-CoA-reductase, we have been
      able to further characterize the glycoprotein(s) involved in the recognition
      process. We have utilized a "cell blotting" technique which lends itself well to
      identifying glycoproteins which are present on the ZGC at the phagocytic stage
      and interactive with the target amoebae. The cell blotting data, combined with
      pharmacological evidence, identifies these glycoproteins as the receptors for
      cannibalistic phagocytosis by the ZGC of D. discoideum.

PMID- 9015351
TI  - V beta activation by HIV Nef protein: detection by a simple amplification
      procedure.
AB  - We previously reported that Nef protein from human immunodeficiency virus (HIV)
      has superantigen properties. However, we were unable to consistently demonstrate
      V beta-specific expansion by Nef using flow cytometry, possibly due to its lower
      mitogenic activity compared to prototypic superantigens. Therefore, we developed
      a simple amplification detection method using immobilized anti-V beta antibodies.
      Human peripheral blood mononuclear cells from adult donors were treated for 24 h
      with Nef and restimulated with immobilized anti-V beta antibodies for an
      additional 72 h. Significant expansion of V beta 5.3 and V beta 18 T-cells were
      detected in Nef-treated cultures, with expansion of V beta 18 occurring with all
      donors tested, and V beta 5.3 expansion occurring in 50% of the donors. Variable
      responses were obtained with V beta 2, V beta 3, and V beta 9. These results were
      confirmed using the more time-consuming method of reverse transcriptase
      polymerase chain reaction (RT-PCR). Thus, this novel, reproducible, and
      relatively simple method can detect V beta-specific expansion by weak
      superantigens.

PMID- 9015352
TI  - First-order phase transition in large single duplex DNA induced by a nonionic
      surfactant.
AB  - The effect of the nonionic surfactant Triton X-100 on the conformational behavior
      of large T4DNA was studied. Through single-molecule observation using
      fluorescence microscopy, we found that T4DNA macromolecules exhibit a discrete
      coil-globule transition with an increase in the Triton X-100 concentration. At
      low surfactant concentrations, all of the DNAs exhibited an elongated coil state,
      whereas only compacted globular DNAs were observed at high molar fractions of
      Triton X-100. The formation of DNA globules was not detected at relatively low
      Triton X-100 concentrations, even above the CMC; DNA collapse occurred in 50-90%
      solutions of Triton X-100. The increase in osmotic pressure in concentrated
      Triton X-100 solutions is considered to be the driving force for the compaction
      of single T4DNAs.

PMID- 9015353
TI  - Identification of two closely related genes, inducible and noninducible carbonyl
      reductases in the rat ovary.
AB  - Two closely related cDNAs encoding carbonyl reductase (CR) were isolated from the
      rat ovary and testis. One (inducible CR, iCR) was rapidly and strongly induced in
      the ovary by pregnant mare serum gonadotropin (PMSG), whereas the other (non
      inducible CR, nCR) was constitutively expressed in the ovary and was not induced
      by PMSG. Both genes were also expressed in the rat testis. The cDNAs of rat iCR
      and nCR encode highly homologous proteins (86% identity in amino acid) with 277
      and 276 amino acid residues, respectively. However, the 5'-upstream regions
      flanking respective genes are completely unrelated to each other except for a
      short (38 bp) overlap. These results indicate the presence of two closely related
      but differently regulated CR genes in rat gonadal tissues. Strong induction of
      iCR by PMSG suggests the importance of the gene in the ovarian follicular
      development.

PMID- 9015354
TI  - Immunological studies of SK2 hybridoma cells microencapsulated with alginate
      poly(L)lysine-alginate (APA) membrane following allogeneic transplantation.
AB  - Microencapsulation of living cells or tissues has been proposed to prevent their
      immune destruction following transplantation. In this study, we examined whether
      SK2 hybridoma cells microencapsulated in an alginate-poly(L)lysine-alginate (APA)
      membrane (APA-SK2 cells) were immunoisolated from the allogeneic host's immune
      system using a cytotoxicity test. The APA membrane inhibited the activation of
      the host's cellular immune response, but did not prevent the production of
      cytotoxic antibodies against entrapped SK2 cells following allogeneic
      transplantation. However, the APA-SK2 cells remained vital in SK2 cell-immunized
      mice as well as in intact mice. We considered that complement regulatory factors
      which were present on cell membrane and had species-specific restriction blocked
      the complement-mediated cell lysis on allogeneic transplantation, since APA-SK2
      cells were destroyed by rabbit anti-SK2 cell antiserum. Our results demonstrated
      that APA membrane could inhibit cell-cell contact between entrapped cells and the
      host's lymphocytes, but could not completely protect the entrapped cells from
      xenogeneic humoral immunity.

PMID- 9015355
TI  - Nucleotide sequence of rat steroidogenic acute regulatory protein complementary
      DNA.
AB  - The steroidogenic acute regulatory (StAR) protein is a key regulator for the
      steroidogenesis in acute response to trophic hormone. A rat complementary DNA of
      the StAR protein was cloned and its complete nucleotide sequence was determined.
      The deduced amino acid sequence of the clone has an additional 86 amino acid
      stretch at amino terminus when it was compared with those sequences in other
      species. The other part of the amino acid sequence has 94% identity to mouse StAR
      protein sequence. Three transcripts (1.3 kb, 1.6 kb, and 3.5 kb) which are
      hybridizing to the clone were detected in testis, ovary and adrenal gland. When
      the cDNA was expressed in COS1 cells, 30 kDa and 47 kDa proteins specific to the
      anti-StAR antibody were detected.

PMID- 9015356
TI  - Activity of UDP-GlcNAc:GlcNAc beta 1-->6(GlcNAc beta 1-->2) Man alpha 1-
      >R[GlcNAc to Man] beta 1-->4N-acetylglucosaminyltransferase VI (GnT VI) from the
      ovaries of Oryzias latipes (Medaka fish).
AB  - UDP-GlcNAc:GlcNAc beta 1-->(GlcNAc beta 1-->2)Man alpha 1-R[GlcNAc to Man] beta 1
      ->4N-acetylglucosaminyltransferase VI (GnT VI) activity was shown to be present
      in crude homogenates of Medaka fish (Oryzias latipes) ovaries using UDP
      [14C]GlcNAc and synthetic GlcNAc beta 1-->6 (GlcNAc beta 1-->2)Man alpha 1-->6Glc
      beta 1-->octyl as substrates. Characterization of this activity showed a pH
      optimum at about pH 7.0 and an absolute requirement for divalent cations. The
      optimum concentration of Mn2+ was at about 25 mM. This finding is the first
      report on GnT VI activity in fish; the enzyme has previously been described only
      in avian tissues.

PMID- 9015357
TI  - Substratum-dependent and region-specific control of attachment and proliferation
      of gastrointestinal epithelial cells in primary serum-free culture.
AB  - A system for the primary serum-free culture of fetal rat gastrointestinal
      epithelial cells was used to examine the role of the extracellular matrix (ECM)
      in the attachment and proliferation of these epithelial cells. Forestomach
      epithelial cells (FSEC) were able to attach to and proliferate on plastic dishes
      without a substratum, while glandular stomach epithelial cells (GSEC) and
      duodenal epithelial cells (DEC) were unable to do so. The presence of a
      substratum promoted the attachment and proliferation of these epithelial cells.
      The effects of various components of the ECM differed depending on the type of
      cell. FSEC attached most efficiently to a substratum of fibronectin, while GSEC
      did so to laminin. DEC attached more efficiently to type I collagen and
      fibronectin than to any other substratum. FSEC proliferated most rapidly on
      laminin, while GSEC and DEC did so on collagen gels. These substrata induced the
      most efficient attachment and proliferation of FSEC, and they were effective in
      promoting the attachment and proliferation of GSEC and DEC in decreasing order of
      efficiency, indicating the existence of a head-to-tail gradient in the response
      of epithelial cells to substrata. The expression of c-myc mRNA in these cells
      differed depending upon the substratum on which they were cultured and the mRNA
      level was well correlated with the extent of the cell proliferation, indicating
      that the cell proliferation is mediated by c-myc gene expression, which is
      regulated by cell-ECM interactions. The results of the present study demonstrate
      that proliferation of gastrointestinal epithelial cells is regulated region
      specifically not only by soluble factors but also by insoluble components of the
      ECM.

PMID- 9015358
TI  - The analgesic domain of IL-2.
AB  - Human recombinant interleukin-2 (IL-2) has been showed to exert an analgesic
      effect and some experiments suggested that opioid receptors were involved.
      Because the aromatic residues at the N-termini of opioid peptides are crucial for
      their binding to the opioid receptors, all nine aromatic residues in IL-2 were
      mutated by site-directed mutagenesis and both the analgesic activity and the
      immune activity of the wild-type and mutated IL-2 were tested. The result
      indicated that there exists a putative analgesic function domain in IL-2, in
      which Phe44, Tyr45, Tyrl07, and Phell7 were essential. These four residues are
      located close together at the tertiary structure level of IL-2.

PMID- 9015359
TI  - Sulfated sialyl Lewis X, the putative L-selectin ligand, detected on endothelial
      cells of high endothelial venules by a distinct set of anti-sialyl Lewis X
      antibodies.
AB  - Endothelial cells of high endothelial venules (HEV) in human peripheral lymph
      nodes expressed a distinct type of sialyl Lewis X antigen, which was detected
      preferentially with a set of anti-sialyl Lewis X antibodies, 2F3, 2H5 and HECA
      452 in immunohistochemistry, while another set of anti-sialyl Lewis X antibodies,
      FH-6 and CSLEX-1, failed to detect it. The adhesion of cells expressing L
      selectin to HEV was inhibited by members of the former set of antibodies in
      Stamper-Woodruff assays performed on frozen sections of human peripheral lymph
      nodes. Transfection of a cultured endothelial cell line with a human alpha1-->3
      fucosyltransferase, Fuc-T VII, resulted in the expression of a distinct type of
      sialyl Lewis X antigen having the reactivity similar to that of HEV; i.e., the
      antigen appearing on the transfectant clone was detectable only with the set of
      2F3, 2H5 and HECA-452, but not with the set of FH-6 and CSLEX-1. Treatment of
      transfectant cells with sodium chlorate, a metabolic inhibitor of sulfation,
      resulted in reactivity to the members of the latter set of antibodies, suggesting
      that sulfation of sialyl Lewis X moiety was the cause of the discrepancy in the
      reactivity of the anti-sialyl Lewis X antibodies. When tested against various
      authentic sulfated sialyl Lewis X determinants, 6-sulfo sialyl Lewis X and 6,6'
      bis-sulfo sialyl Lewis X were found to be reactive to the antibodies, 2F3, 2H5
      and HECA-452, but not with antibodies FH-6 and CSLEX-1, suggesting that the
      distinct type of sialyl Lewis X determinant on the HEV endothelial cells and Fuc
      T VII-transfected endothelial cell clone are mainly 6-sulfo and/or 6,6'-bis-sulfo
      sialyl Lewis X determinants.

PMID- 9015360
TI  - Myosin binding subunit of smooth muscle myosin phosphatase at the cell-cell
      adhesion sites in MDCK cells.
AB  - We examined the intracellular localization of the myosin binding subunit (MBS) of
      smooth muscle myosin phosphatase. In MDCK cells in a confluent monolayer of
      polarized epithelial sheet, MBS was concentrated to the cell-cell adhesion sites.
      Double-immunofluorescence analysis with anti-MBS and anti-beta-catenin antibodies
      showed that MBS was mainly localized at the adherens junction. Furthermore, MBS
      was translocated reversibly between the cytosol and the cell-cell adhesion sites
      during the formation and disappearance of cell-cell contacts. These data suggest
      that MBS may play an important role in the regulation of the cell-cell adhesion.

PMID- 9015361
TI  - Inhibition of HIV-1 protease by oxim derivatives.
AB  - In cell-free proteolytic processing using recombinant HIV-1 protease and Gag
      precursor polypeptide, certain simple oxim derivatives containing
      halogenomethylketone and phenyl moieties displayed HIV-1 protease inhibitory
      activity. Their Ki values ranged from 2.1 microM to 6.3 microM and they did not
      inhibit significantly other aspartic acid proteases. Both the
      halogenomethylketone moiety and the oxim structure were essential for the
      observed inhibition. Molecular modeling analysis suggested that these compounds
      are recognized by the HIV-1 protease as the P1 and P1' part of the substrate. In
      addition, one potent derivative showed inhibition of viral maturation in HIV
      1IIIB chronically infected Molt-4 cells. These results indicate that it is
      possible to develop new and specific nonpeptidyl HIV protease inhibitors of low
      molecular weight.

PMID- 9015362
TI  - Metabolism of farnesol: phosphorylation of farnesol by rat liver microsomal and
      peroxisomal fractions.
AB  - In this study we provide evidence for the first time that rat liver microsomal
      and peroxisomal fractions are able to phosphorylate free farnesol to its
      diphosphate ester in a CTP dependent manner. The farnesyl diphosphate (FPP)
      kinase activity is decreased in whole liver homogenates obtained from rats
      treated with cholesterol and unchanged in homogenates obtained from rats treated
      with cholestyramine. In contrast, farnesyl pyrophosphatase (FPPase) activity, an
      enzyme which specifically hydrolyzes FPP to farnesol is only found in the
      microsomal fraction and is unaffected by treatment of rats with cholesterol or
      cholestyramine. In addition, we also demonstrate that farnesol can be oxidized to
      a prenyl aldehyde, presumably by an alcohol dehydrogenase (ADH), and that this
      activity resides in the mitochondrial and peroxisomal fractions.

PMID- 9015363
TI  - Transcription regulation of the PDGF A-chain gene by first intron elements.
AB  - A cis-acting regulatory region within the first intron of the human platelet
      derived growth factor (PDGF) A-chain gene has been identified that functions to
      negatively regulate transcription of PDGF A-chain promoter/CAT reporter
      constructs in both A172 and HeLa cells and that functions independent of
      position, orientation, and promoter context. Further dissection of this region
      revealed several independently acting negative regulatory elements that exhibited
      cell-type specificity. These results suggest that the first intron of the PDGF A
      chain gene contains negative regulatory elements that may cooperate to regulate
      the cell-type specific expression of the PDGF A-chain gene.

PMID- 9015364
TI  - The effects of IL-1 on mitogen-activated protein kinases in rabbit articular
      chondrocytes.
AB  - IL-1-activated chondrocytes express a large number of genes which contribute to
      cartilage degradation. The signaling pathways activated in response to IL-1 in
      these cells are not well-defined. We examined the effects of IL-1 and other
      stimuli on the mitogen activated protein kinase (MAPK) pathways in rabbit
      articular chondrocytes. We demonstrate that IL-1 activates three MAPKs, ERK, JNK
      and p38, in a time and dose-dependent manner. Activation is maximal by 15 minutes
      and returns to baseline levels by 1 hour. Maximal activation of ERK and p38
      occurs with 1 ng/ml IL-1 whereas activation of JNK requires 10-fold higher
      levels. In contrast to IL-1, the PKC activator, PDBu preferentially activates ERK
      while TNF alpha preferentially activates JNK. LPS and TGF beta fail to stimulate
      any of the kinases examined. These results suggest that activation of the various
      MAPK pathways is important in the response of chondrocytes to IL-1, cytokines and
      growth factors.

PMID- 9015365
TI  - Cell-cycle regulated expression of Rap1 in regenerating liver.
AB  - Rap1 proteins are capable of competing with Ras p21 for binding to effectors, and
      of antagonizing some Ras-induced effects, but their participation in normal
      growth regulation has not been established. The level of Rap1 protein and the
      expression of the rap1A gene were examined by immunoblotting and Northern
      analysis during the regenerative growth response in rat liver following partial
      hepatectomy. Protein and mRNA were significantly down-regulated prior to and
      during the onset of DNA synthesis. The timing of this effect is consistent with a
      model in which expression of Rap1 is turned off or down to allow the initiation
      of proliferation.

PMID- 9015366
TI  - Escherichia coli rnpB promoter mutants altered in stringent response.
AB  - The promoter of the rnpB gene (encoding the RNA component of Escherichia coli
      RNase P) shares a consensus discriminator sequence, located between the -10
      hexamer sequence and the transcription start site, with other promoters whose
      activities are repressed upon stringent condition. Under stringent conditions
      induced by seryl-tRNA starvation the transcription of the rnpB gene was repressed
      in wild type E. coli but not in a relaxed strain carrying a relA- mutation. Site
      directed mutagenesis was carried out to examine sequences of the rnpB promoter
      necessary for stringent control. The results indicate that the discriminator
      region is responsible for the transcription repression of the rnpB gene during
      the stringent response and that both the content and position of GC pairs in the
      region determine the strength of negative stringent signals.

PMID- 9015367
TI  - Correction of the DNA repair defect in Fanconi anemia complementation groups A
      and D cells.
AB  - We have previously isolated from Fanconi anemia, complementation groups A (FA-A)
      and D (FA-D) cells, a DNA endonuclease complex which is defective in its ability
      to incise DNA containing interstrand cross-links produced by psoralen plus UVA
      light. The repair capabilities of the FA complexes, compared with those of the
      corresponding normal complex, have now been examined using two types of
      complementation analysis. First, introduction of the normal complex, by
      electroporation, into 8-methoxypsoralen (8-MOP) plus UVA treated FA-A and FA-D
      cells resulted in correction of their repair defect, determined by measuring
      repair-related unscheduled DNA synthesis (UDS). The FA-A and FA-D complexes could
      similarly complement the repair defect in each others' cells, but not in their
      own. Second, mixing the normal with the FA-A and FA-D complexes, or the FA-A with
      the FA-D complex, in a cell-free system resulted in correction of the defect in
      ability of these FA complexes to incise damaged DNA. These results indicate that
      the normal complex contains the proteins needed to correct the DNA repair defect
      in FA-A and FA-D cells and that the FA-A and FA-D complexes contain the protein
      needed to complement the repair defect in each other.

PMID- 9015368
TI  - The role of disulfide bond C191-C220 in trypsin and chymotrypsin.
AB  - Serine proteases of the chymotrypsin family contain three conserved disulfide
      bonds: C42-C58, C168-C182, and C191-C220. C191-C220 connects the loops around the
      substrate binding pocket. Using site directed mutagenesis, cysteines of this
      disulfide bridge were replaced by alanines in trypsin, in chymotrypsin, and in Tr
      ->Ch-[S1+L1+L2+Y172W], a mutant trypsin with high chymotrypsin like activity. The
      functional role of this "active site" disulfide was assessed by comparing the
      catalytic properties of wild-type and mutant enzymes. Its removal from all three
      proteases caused a decrease in kcat/KM of two to three orders of magnitude,
      mainly as a consequence of a dramatic increase in KM. The pH dependence of the
      activity also changed: the rather wide pH optimum, characteristic of the wild
      type enzymes (especially trypsin), narrowed since the pKa in the alkaline region
      shifted downwards. Results show that C191-C220 is necessary for the high activity
      of both trypsin and chymotrypsin. By contrast, elimination of this disulfide
      bridge greatly decreased the specificity of trypsin and of Tr-->Ch
      [S1+L1+L2+Y172W], but had no significant change on that of chymotrypsin.

PMID- 9015369
TI  - Regulation of C1-inhibitor function by binding to type IV collagen and heparin.
AB  - Serpins inhibit proteinases by a branched pathway, in which an intermediate
      serpin-proteinase complex can either form a stable covalent serpin-proteinase
      complex or produce reactive center cleaved serpin in a substrate reaction. It was
      tested whether these competing reactions could be regulated for the serpin C1
      inhibitor by ligand binding. C1-inhibitor bound to type IV collagen, laminin, and
      entactin. Type IV collagen (10 microg/ml) caused an increase in the stoichiometry
      of inhibition for C1s inhibition by C1-inhibitor to 1.48 from 1.09 in the absence
      of ligand. A dose-dependent increase in the stoichiometry up to 1.27 in the
      presence of 100 microg/ml heparin was also observed. At low ionic strength the
      stoichiometry increased to 2.55. These data provide the first report that C1
      inhibitor can bind to type IV collagen and also show that C 1-inhibitor can be
      regulated by ligand binding.

PMID- 9015370
TI  - Detection of membrane associated thioredoxin on human cell lines.
AB  - Thioredoxin (TRX) is a ubiquitous dithiol-oxidoreduction enzyme broadly expressed
      in cells from prokaryote to eukaryote organisms. Human thioredoxin (human TRX)
      gene, previously cloned in our laboratory, codes for a 12-kDa protein found in
      the culture supernatant of several hemopoietic human cell lines. This protein is
      secreted by a nonclassical pathway. The role of the secreted enzyme as a
      signalling soluble mediator was demonstrated, but nothing is known about a
      membrane associated form of thioredoxin which could be involved in cell/cell
      contacts and accessory signal function. Thus, we performed experiments to
      determine if human TRX is also expressed at the cell surface. We report here
      positive results based upon indirect immunofluorescence flow cytometric analysis
      of different human cell lines (HeLa, U 937, Jurkat, 3B6, Daudi and Raji) using a
      cross reactive sheep anti E. coli TRX polyclonal antibody demonstrating a
      significant expression of human TRX at the surface of human cells.

PMID- 9015371
TI  - The nucleotide sequence of the translated and untranslated regions of a cDNA for
      myotoxin a from the venom of prairie rattlesnake (Crotalus viridis viridis).
AB  - Myotoxin a, isolated from C. viridis viridis venom, is a myonecrotizing agent
      present in many snake venoms. A cDNA library was prepared from mRNA obtained from
      the venom glands of a C. viridis viridis. The complete base sequence of a cDNA
      corresponding to an mRNA encoding myotoxin a was determined. The 5' untranslated
      region has 15 nucleotides, while the 3' untranslated region has 109 nucleotides.
      The translated portion of the myotoxin a cDNA encodes a start methionine, a
      signal peptide, the myotoxin a peptide sequence, and an additional lysine
      residue. It is likely that myotoxin a is secreted as the cDNA encodes a signal
      peptide immediately 5' to the myotoxin a peptide code.

PMID- 9015372
TI  - The mitochondrial sulfonylurea receptor: identification and characterization.
AB  - Biochemical identification of mitochondrial sulfonylurea receptors has been
      carried out through binding studies performed with [3H]glibenclamide. The
      presence of a single class of low affinity binding sites for glibenclamide in the
      inner mitochondrial membrane has been found, with a KD of 360 +/- 48 nM and BMAX
      of 48 +/- 7 pmoles/mg in beef heart mitochondria. Glibenclamide binding was
      affected by other sulfonylureas (glipizide, glisoxepide) but not by potassium
      channel openers (diazoxide, pinacidil, RP66471). In both rat liver and beef heart
      mitochondria adenine nucleotides (ATP, ADP, AMP) and nucleotide analogs (triazine
      dyes) produced large inhibition (from 60 to 80%) of [3H]glibenclamide binding.
      Photoaffinity labeling of submitochondrial particles with [125I]-glibenclamide
      revealed a single specifically labeled polypeptide band of 28 kDa by SDS-PAGE
      that is postulated to be (or to form a part of) the mitochondrial sulfonylurea
      receptor.

PMID- 9015373
TI  - A flickery block of a K+ channel mediated by extracellular Ca2+ and other
      agonists of the Ca2+-sensing receptors in dispersed bovine parathyroid cells.
AB  - Single K+ channel activities in parathyroid cells were studied using the patch
      clamp technique. A K+ channel modulated by external Ca2+ (Ca2+o) was identified.
      This channel had a unitary conductance of 109pS at 150 mM K+o in the pipette
      solution. An increase in Ca2+o from 0.5-0.75 to 2-3 mM induced a flickery partial
      block of the channel over a wide voltage range. The mechanism of channel blockade
      included a significant increase in the number of closings per burst and a
      reduction of the mean open times. Addition of other divalent and polyvalent
      agonists of the Ca2+-sensing receptor (CaR) induced a similar channel blockade.
      With its typical characteristics and flickery block by CaR agonists, this channel
      differs from previously described types of K+ channels. It is probably strongly
      coupled to the CaR and may contribute to the depolarization of parathyroid cells
      which is known to occur at elevated levels of Ca2+o.

PMID- 9015374
TI  - Nutrient regulation of the intestinal Na+/glucose co-transporter (SGLT1) gene
      expression.
AB  - It is known that dietary carbohydrates regulate the activity of the intestinal
      SGLT1. We have demonstrated that modifications in SGLT1 activity are due to
      alterations in SGLT1 expression in response to the sugar content of the diet. To
      assess the correlation between changes in the activity of SGLT1 and the abundance
      of SGLT1 protein, we have employed a method for the quantitative measurement of
      immunoreactive proteins. A calibration curve has been constructed using either a
      nonadecapeptide (amino acids 402-420), or a recombinant protein corresponding to
      amino acids 554-640 of the SGLT1 sequence. Immunoblotting the protein samples
      concurrently with specific quantities of either the peptide or recombinant
      standard, using antibodies raised against these antigens, enabled accurate
      quantification of the absolute amounts of immunoreactive protein in the samples.
      The amount of SGLT1 protein correlates well with measurements of SGLT1 activity.
      The modulation of the activity of SGLT1 in response to lumenal sugars is due to
      corresponding changes in the absolute levels of SGLT1 protein.

PMID- 9015375
TI  - Varied prevalence of age-associated mitochondrial DNA deletions in different
      species and tissues: a comparison between human and rat.
AB  - The prevalence in tissues of mtDNA deletions was compared by PCR between humans
      and rats of similar "biological ages". Pairs of species-specific primers were
      used which spanned similar portions of the human and rat mtDNA genomes. There
      were much fewer PCR products amplified from rat mtDNA than from human mtDNA in
      each of the three tissues initially analysed: heart, liver and skeletal muscle.
      By contrast, many more PCR products were amplified from rat kidney than from
      human kidney. Therefore, while there were far more deletions in heart, liver and
      skeletal muscle of humans than in corresponding rat tissues, the prevalence of
      mtDNA deletions was markedly less in human kidney than in rat kidney. The data
      also indicate that human kidney contains less mtDNA deletions than heart, liver
      and skeletal muscle in humans; whereas in rat kidney there are more mtDNA
      deletions than in those three tissues of rat. It is further suggested that, when
      utilising rodents as experimental models for human ageing, the appropriate
      tissues should be considered, since not all tissues of rats accumulate mtDNA
      mutations in the same manner as those of humans.

PMID- 9015376
TI  - Effects of the murine L929 and L1210 cell lines on nitric oxide and TNF-alpha
      production by RAW 264.7 murine macrophages.
AB  - Co-cultures of the murine macrophagic cell line RAW 264.7 with the L929
      fibrosarcoma cell line, but not with the leukemia L1210 cell line, showed
      enhanced NO production over control RAW 264.7 cells. This potentiating effect,
      which was observed in detectably mycoplasma-free conditions and required low
      concentrations of recombinant murine IFN-gamma, was due to soluble factors
      released from L929 cells and not to physical contact between the two cell types.
      The soluble factors were able to induce TNF-alpha in the macrophages and to
      potentiate the TNF-alpha release induced by IFN-gamma. Increased generation of NO
      in RAW 264.7 cells co-cultured with L929 cells was prevented by a neutralizing
      anti-TNF-alpha antibody, suggesting that TNF-alpha is an autocrine factor for
      iNOS expression in these conditions. Also the L929 cell line showed a 4- to 5
      fold enhanced NO production following co-culture with RAW 264.7 cells, thus
      indicating that exposure of tumor cells to macrophages can lead to an increased
      iNOS expression in tumor cells themselves.

PMID- 9015377
TI  - Mutations in the ROMK gene in antenatal Bartter syndrome are associated with
      impaired K+ channel function.
AB  - Children with the antenatal variant of Bartter syndrome present the typical
      pattern of impaired salt reabsorption in the thick ascending limb of Henle's loop
      (TALH) resulting in marked ante- and postnatal salt wasting. In some of these
      patients mutations in the renal potassium channel ROMK (KCNJ1) have been found.
      We analyzed the electrophysiological function of five recently described ROMK
      channel mutations (V72E, D108H, P110L, A198T and V315G). In whole cell patch
      clamp recordings wildtype rat ROMK1 exhibited K+ currents of >1 nA at a membrane
      potential of 100 mV when transfected into COS-7 kidney cells. These currents were
      sensitive to external Ba2+ and internal Mg2+, which are typical features of the
      inwardly rectifying KIR channel. In contrast mutated ROMK1 cDNAs expressed either
      no or only infrequently small currents (<200 pA). Loss of tubular K+ channel
      function probably prevents apical membrane potassium recycling with secondary
      inhibition of Na-K-2Cl-cotransport in the TALH. We conclude that mutations in the
      potassium channel ROMK are the primary events causing renal salt wasting in a
      subset of patients with the antenatal variant of Bartter syndrome.

PMID- 9015378
TI  - Functional characterization of a novel type of 1 alpha,25-dihydroxyvitamin D3
      response element identified in the mouse c-fos promoter.
AB  - The seco-steroid 1 alpha,25-dihydroxyvitamin D3 (VD) is known to inhibit cellular
      proliferation and to induce differentiation as well as programmed cell death
      (apoptosis). VD is the ligand of the transcription factor VDR, which is a member
      of the nuclear receptor superfamily. Primary VD responding genes contain a VD
      response element (VDRE), on which VDR binds as a dimeric complex. The main
      heterodimeric partner of VDR is the retinoid X receptor (RXR) and the majority of
      the known natural VDREs are formed by a direct repeat of hexameric core binding
      motifs spaced by 3 nucleotides. Most of the genes carrying DR3-type VDREs are
      associated with the hormone's classical function, which is the regulation of
      calcium homeostasis. Recently, it has been found that inverted palindromic
      arrangements spaced by 9 nucleotides also form functional VDREs. This paper
      reports the identification of a novel IP9-type VDRE in the mouse c-fos promoter.
      This elements is bound with high affinity by VDR-RXR heterodimers and responds at
      10-fold lower concentrations to the potent anti-proliferative VD analogue EB1089
      than to VD. This suggests that VD may be directly involved in the transcriptional
      regulation of the cell cycle via the activation of the c-fos gene.

PMID- 9015379
TI  - Free cytosolic calcium levels modify intracellular pH in rat pancreatic acini.
AB  - We have used BCECF- or Fura-2-loaded rat pancreatic acinar cells to investigate
      the relationship between Ca2+ mobilization and intracellular pH (pHi). Ca2+
      mobilizing agonists CCK-8 and ACh induced a transient acidification totally
      dependent on release of Ca2+ from internal stores. Employment of different
      physiological tools including ionomycin and thapsigargin to increase the
      cytosolic Ca2+ concentration and capacitative calcium influx also induced
      cellular acidification. Application of 1mM LaCl3 reduced the CCK-8-evoked
      acidification. These data indicate that the mobilization of intracellular Ca2+
      stores by CCK-8 decreases cellular pH by Ca2+/H+ exchanger.

PMID- 9015380
TI  - A dual affinity tag on the 64-kDa Nlt1p subunit allows the rapid characterization
      of mutant yeast oligosaccharyl transferase complexes.
AB  - Oligosaccharyl transferase catalyzes the glycosylation of selected asparagine
      residues of nascent polypeptide chains as they are translocated into the lumen of
      the endoplasmic reticulum. To date, this enzyme has been purified from a number
      of eukaryotic organisms. Purification of transferase activity has yielded
      polypeptide complexes of three to six subunits depending on the source organism.
      Here we present the purification of an affinity-tagged version of the enzyme
      complex from a membrane protein fraction of the yeast Saccharomyces cerevisiae. A
      yeast strain was created in which the essential 64-kDa glycoprotein Nlt1p subunit
      of the oligosaccharyl transferase was modified by the addition of a 22-residue
      carboxy-terminal affinity tag; the tag included both an 8-residue FLAG epitope
      and a 6-residue histidine motif. Facile purification of the oligosaccharyl
      transferase was achieved using affinity chromatography media specific for each
      segment of the tag. The enzyme was purified as a heteromeric complex of five
      subunits in agreement with previously reported characterizations of the yeast
      transferase. Yeast strains bearing affinity-tagged enzyme subunits allow the
      rapid characterization of native and mutant transferase complexes.

PMID- 9015381
TI  - Insulin-mimetic action of vanadium compounds on osteoblast-like cells in culture.
AB  - Vanadium compounds mimic insulin actions in different cell types. The present
      study concerns the insulin-like effects of three vanadium(V) derivatives and one
      vanadium(IV) complex on osteoblast-like (UMR106 and MC3T3E1) cells in culture.
      The vanadium oxalate and vanadium citrate complexes hydrolyzed completely under
      the culture conditions, whereas more than 40% of the vanadium tartrate and
      nitrilotriacetate complexes remained. Vanadate, as well as vanadium oxalate,
      citrate, and tartrate complexes enhanced cell proliferation (as measured by the
      crystal violet assay), glucose consumption, and protein content in UMR106 and
      MC3T3E1 osteoblast-like cells. The vanadium nitrilotriacetate complex (the only
      peroxo complex tested) stimulated cell proliferation in UMR106 but not in MC3T3E1
      cells. This derivative strongly transformed the morphology of the MC3T3E1 cells.
      All vanadium(V) compounds inhibited cell differentiation (alkaline phosphatase
      activity) in UMR106 cells. Our data are consistent with the interpretation that
      vanadium oxalate and citrate complexes hydrolyze to vanadate. Vanadium
      nitrilotriacetate would appear to be toxic for normal MC3T3E1 osteoblasts. In
      contrast, the vanadium tartrate complex induced a proliferative effect; however,
      it did not alter cell differentiation.

PMID- 9015382
TI  - Myeloperoxidase-dependent generation of a tyrosine peroxide by neutrophils.
AB  - It has recently been shown that tyrosyl radicals react with superoxide to form a
      peroxide adduct of tyrosine. Since myeloperoxidase oxidizes tyrosine to its
      radical, and neutrophils and monocytes contain myeloperoxidase as well as produce
      superoxide, we have investigated whether tyrosine peroxide could be a significant
      product of tyrosine oxidation by these cells. Oxidation of tyrosine by purified
      myeloperoxidase and a superoxide-generating system, and by stimulated human
      neutrophils, was found to generate peroxide adducts as detected in the xylenol
      orange (FOX) assay and by HPLC. Superoxide, hydrogen peroxide, and
      myeloperoxidase were required for formation of the peroxide. Dityrosine was also
      formed in each system, and in the presence of superoxide dismutase, suppression
      of tyrosine peroxide formation gave elevated formation of dityrosine.
      Quantitative estimates indicate that at physiological tyrosine concentration the
      peroxide is likely to be formed in preference to dityrosine and to be a
      significant product of neutrophils. This metastable peroxide therefore has the
      potential to contribute to neutrophil- or monocyte-mediated tissue injury.

PMID- 9015383
TI  - Cloning, sequencing, and expression of Arthrobacter protophormiae endo-beta-N
      acetylglucosaminidase in Escherichia coli.
AB  - The gene encoding endo-beta-N-acetylglucosaminidase from Arthrobacter
      protophormiae (Endo-A) was cloned, and its nucleotide sequence was determined. A
      single open reading frame consisting of 1935 base pairs and encoding a
      polypeptide composed of signal peptides of 24 amino acids and a mature protein of
      621 amino acids was found. The primary structure of Endo-A exhibited significant
      homology with FO1F.10 gene product from Caenorhabditis elegans and weak homology
      with peptide-N4-(N-acetyl-beta-D-glucosaminyl)asparagine amidase from
      Flavobacterium meningosepticum and chitinase from Streptomyces olivaceoviridis.
      However, the enzyme had no significant homology with any previously reported endo
      beta-N-acetylglucosaminidases. Transformed Escherichia coli cells carrying the
      4.5-kb fragment expressed Endo-A activity. This enzyme activity was detected in
      the medium as well as in the periplasmic space of cells under the control of the
      Endo-A gene promoter. The recombinant Endo-A was efficiently isolated from the
      periplasmic space of the cells. N-terminal sequence analysis revealed that native
      and recombinant Endo-A have the same N-terminus. Recombinant and native Endo-A
      also showed very similar optimum pH profiles and transglycosylation activity.

PMID- 9015384
TI  - Purification and characterization of hepatic aldehyde oxidase in male and female
      mice.
AB  - To examine whether the hepatic aldehyde oxidases of male and female mice, which
      exhibit sex-related differences in benzaldehyde oxidation, are qualitatively
      different, we purified the enzymes from untreated male and female ddy mice and
      testosterone-pretreated female mice by sequential chromatography of benzamidine
      Sepharose 6B and DEAE-5PW columns and characterized the enzymes. Purified enzymes
      from untreated male and female mice and from testosterone-treated females gave a
      single protein band at M(r) 265K and M(r) 138K on native and SDS-polyacrylamide
      gradient gel electrophoresis, respectively. The susceptibilities of the enzymes
      from both sexes to inhibitors such as menadione, norharman, quinacrine,
      estradiol, and SKF 525-A were also indistinguishable. However, the K(m) values
      for benzaldehyde, p-dimethylaminocinnamaldehyde, and 2-hydroxypyrimidine were two
      to fourfold higher in the untreated female enzyme than in the untreated male
      enzyme, while the testosterone-induced female enzyme showed K(m) values similar
      to those of the male enzyme. These results indicate that the hepatic aldehyde
      oxidases of the sexes are quite similar with respect to molecular size and
      susceptibility to inhibitors, but their kinetic properties are somewhat
      different, suggesting the existence of microheterogeneity in sex differences. It
      also suggests that treatment of female mice with testosterone might induce the
      male-type enzyme.

PMID- 9015385
TI  - Cytochrome P450 2C11: Escherichia coli expression, purification, functional
      characterization, and mechanism-based inactivation of the enzyme.
AB  - The male-specific P450 enzyme CYP 2C11, whose expression is developmentally and
      hormonally regulated, is the major steroid 16alpha-hydroxylase of the untreated
      rat liver. The enzyme metabolizes a host of substrates, including mechanism-based
      inactivators, such as 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine
      (DDEP) and spironolactone (SPL). Structural and functional characterization of
      the specific mode of such inactivation, however, requires sufficient quantities
      of the fully purified enzyme. Although several laboratories including our own
      have isolated and purified the enzyme from male rats, the yields are typically
      low and of the order of 1%. For these reasons, we chose to heterologously express
      the enzyme in Escherichia coli. The full-length cDNA was excised from the yeast
      vector pD2M1 and cloned into the plasmid vector pCW after appropriate
      modifications for optimal expression in E. coli. The enzyme was isolated and
      purified from E. coli membranes in relatively high yields (approximately 60%) and
      relatively high specific content (19 nmol/mg protein). The purified recombinant
      enzyme had spectral and functional characteristics comparable to those reported
      for the native rat liver enzyme, including mechanism-based inactivation by DDEP
      and SPL. Studies with 14C-heme-labeled enzyme indicated that the major mode of
      DDEP inactivation was via heme-N-ethylation. On the other hand, studies with
      radiolabeled SPL-SH (the proximal inactivating deacetylated metabolite of SPL)
      revealed that although both [22-14C]SPL-SH and SPL-35SH inactivated the enzyme,
      only SPL-35SH was found to irreversibly radiolabel the 2C11 protein. The latter
      findings thus suggest that during mechanism-based inactivation of 2C11, the thiol
      moiety of SPL-SH is oxidatively activated to a species that attacks the 2C11
      protein during or after cleavage from the thiosteroid. Thus, these modes of
      mechanism-based 2C11 inactivation by DDEP and SPL-SH considerably differ from the
      corresponding modes of P450 3A inactivation by these agents, wherein heme
      modification of the protein predominates.

PMID- 9015386
TI  - Gene structure of mouse Cyp3a11: evidence for an enhancer element within its 5'
      flanking sequences.
AB  - A mouse Cyp3a11 gene was isolated from a mouse sperm DNA library with mouse
      Cyp3a11 cDNA as a probe. The nucleotide sequences determined for the gene and the
      5' flanking region revealed that the mouse Cyp3a11 gene was composed of 13 exons
      and 12 introns. The exons spun about 23 kb. The nucleotide sequence of the exons
      was completely identical to Cyp3a11 cDNA. Within the 5' flanking sequence,
      putative binding sites of several transcriptional factors were found. Transient
      transfection assays were carried out with HepG2 cells, a human hepatoma cell
      line, using constructs containing different lengths of 5' flanking sequence fused
      to a reporter, chloramphenicol acetyltransferase gene. The results showed that a
      cis-acting element(s) was located from -1609 to -907.

PMID- 9015387
TI  - Association of HSP60-like proteins with the L-system amino acid transporter.
AB  - The carrier protein(s) responsible for mammalian L-system amino acid transport
      has not been identified. Chronic lymphocytic leukemia (CLL) B-lymphocytes have
      markedly diminished L-system transport which is restored after treatment with 12
      O-tetradecanoyl-phorbol-13-acetate (TPA). Six candidate L-system related plasma
      membrane proteins were identified in TPA-treated CLL-cells using an L-system
      photoprobe and ultra-high-resolution two-dimensional gel electrophoresis. In the
      current studies, two candidate L-system related proteins were obtained from
      preparative giant two dimensional gels, and the amino acid sequences of peptide
      fragments from these proteins were determined by Edman degradation. These
      proteins, forming a doublet on the gels at an apparent size of 40 kDa and pI
      5.85, had sequence homology to the mitochondrial heat shock protein 60 (hsp60).
      The presence of these proteins in CLL lymphocyte plasma membranes was confirmed
      by immunoblotting with antibodies to hsp60. These observations indicate that an
      hsp60 homologue is associated with the L-system amino acid transporter.

PMID- 9015388
TI  - Mutation of conserved residues in the NADP(H)-binding domain of the proton
      translocating pyridine nucleotide transhydrogenase of Escherichia coli.
AB  - Possible NADP(H)-binding sites of the beta subunit of the pyridine nucleotide
      transhydrogenase of Escherichia coli were examined by site-directed mutagenesis.
      The sequence of the beta subunit at positions 314-350 showed several features
      typical of NADP(H)-binding sites. Mutation of betaGly314, the first glycine
      residue of the GXGXXV motif, and of betaArg350, which probably interacts with the
      2'-phosphate of the substrate NADP(H), resulted in drastic loss of enzyme
      activity. The loss of activity in the betaArg350 mutants was not due to loss of
      ability to bind NADP(H). Several residues (betaVal319, betaGly337, betaHis345,
      and betaArg350) were mutated to make the sequence more similar to that of a
      NAD(H)-binding site. The introduction of multiple mutations resulted in improper
      assembly of the enzyme and decreased incorporation into the membrane. The GXGXXG
      motif, typical of beta alphabeta nucleotide-binding folds, in the sequence of the
      beta subunit at positions 274-279 was mutated without causing major changes in
      transhydrogenase activities. It is unlikely to be part of a nucleotide-binding
      domain. Deletion of the carboxy-terminal 32 amino acids of the beta subunit, a
      possible nucleotide-binding site, prevented assembly and incorporation of the
      truncated enzyme into the cytoplasmic membrane of E. coli.

PMID- 9015389
TI  - Inhibition of estrogen-induced activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) in the MCF-7 human breast cancer and other cell lines transfected with
      vitellogenin A2 gene promoter constructs.
AB  - The antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was
      investigated in several cell lines using transient transfection assays and
      constructs containing 5'-regulatory sequences from the estrogen (E2)-responsive
      vitellogenin (Vit) A2 gene linked to the bacterial chloramphenicol
      acetyltransferase (CAT) reporter gene. TCDD significantly inhibited CAT activity
      induced by E2 in MCF-7 human breast cancer cells transiently transfected with 5'
      deletion plasmids containing the homologous promoter [(-821/+14)- and (-482/+14)
      CAT] or the heterologous thymidine kinase (tk) promoter [(-821/-87)tk-, (-482/
      87)tk-, (-397/-87)tk-, and (-331/-87)tk-CAT]. In parallel experiments using wild
      type mouse Hepa 1c1c7 and human HeLa cells cotransfected with a human estrogen
      receptor expression plasmid, TCDD also inhibited E2-induced CAT activity. The
      role of the nuclear Ah receptor complex was confirmed by results of the following
      studies using MCF-7 or mouse Hepa 1c1c7 cells transiently transfected with E2
      responsive Vit A2 gene 5'-promoter constructs: (i) for a series of Ah receptor
      ligands, there was a correlation between their antiestrogenic activity in MCF-7
      cells and their rank order binding affinity for the Ah receptor; (ii) alpha
      naphthoflavone, an Ah receptor antagonist, inhibited the antiestrogenic activity
      of TCDD in MCF-7 cells; and (iii) TCDD inhibited E2-induced CAT activity in Ah
      responsive wild-type but not in Ah-nonresponsive class 2 mutant Hepa 1c1c7 cells.
      The antiestrogenic activity of TCDD was also observed in cells which transiently
      overexpressed the human estrogen receptor (ER), suggesting that the mechanism
      does not involve downregulation of the ER by TCDD.

PMID- 9015390
TI  - Inactivation and recovery of nitric oxide synthetic capability in cytokine
      induced RAW 264.7 cells treated with "irreversible" NO synthase inhibitors.
AB  - As measured at 100 microM extracellular arginine, aminoguanidine produced a time-
      and concentration-dependent inactivation of nitric oxide (NO) synthesis by
      cytokine-induced RAW cells. Inactivation obeyed first-order kinetics and occurred
      at a maximal rate of 0.22 min(-1) with a half-maximal inactivation rate observed
      at a concentration of 670 microM aminoguanidine (K(I) value). Inactivation of NO
      synthetic activity in the presence of N(G)-methyl-L-arginine similarly followed
      first-order kinetics with a maximal inactivation rate of 0.07 min(-1) and a K(I)
      value of 170 microM. Inactivation of NO synthetic activity in the presence of
      diphenyliodonium chloride occurred with a maximal inactivation rate of 0.24 min(
      1) with a K(I) value of 14 microM. Diphenyliodonium chloride also produced a
      first-order rate of inactivation of cytokine-inducible nitric oxide synthase
      (iNOS) activity affinity purified from cytokine-induced RAW cells with a maximal
      inactivation rate of its cytochrome c reductase activity of 0.24 min(-1) with a
      K(I) value of 18 microM. Cytokine-induced RAW cells were treated with
      aminoguanidine, N(G)-methyl-L-arginine, and diphenyliodonium chloride at
      concentrations and for a time sufficient to completely inactivate NO synthesis by
      the cells and were allowed to recover in drug-free medium. Despite the presence
      of cycloheximide, NO synthetic rate recovered from 70 to 90% of its pretreatment
      activity over 4 h in cells exposed to either aminoguanidine or N(G)-methyl-L
      arginine but did not recover from exposure to diphenyliodonium chloride. Analysis
      by sucrose density gradient centrifugation of the cytochrome c reductase and
      citrulline-forming activities in extracts of cells recovered from aminoguanidine
      treatment revealed that recovery was accompanied by a diminished population of
      iNOS monomers with an increased population of iNOS dimers. This observation is
      consistent with the hypothesis that for the mechanism-based inactivator
      aminoguanidine, functional dimers can be assembled from "drug-undamaged" monomers
      during the recovery period.

PMID- 9015391
TI  - Reversal of the nucleotide specificity of ketol acid reductoisomerase by site
      directed mutagenesis identifies the NADPH binding site.
AB  - Analysis of the published amino acid sequences of the enzyme ketol acid
      reductoisomerase (KARI) from seven organisms identified three regions with highly
      conserved sequences. One of these regions is predicted to be the dinucleotide
      fold where NADPH binds. In order to confirm that this region did include the
      NADPH binding site, we used oligonucleotide-mediated site-directed mutagenesis to
      study the function of specific amino acids in this region in terms of their
      interactions with NADPH. Four positively charged amino acids, R68, K69, K75, and
      R76, were mutated singly, in different combinations, and finally as a quartet in
      order to evaluate electrostatic interactions with NADPH. Mutation of each of the
      arginines singly to glutamine results in a 60- to 100-fold reduction in
      k(cat)/K(m) for NADPH. Mutation of each of the lysines singly does not
      significantly alter the steady state kinetic parameters associated with NADPH.
      None of these mutations significantly alters the affinity of the enzyme for NADH.
      After looking at double mutations of these four amino acids, we constructed the
      quadruplet mutant R68DK69LK75VR76D. This mutant has K(m) and k(cat) values of
      19.3 microM and 5.3 min(-1) for NADH, which compares to 207 microM and 0.11 min(
      1) for the wild-type enzyme. For the quadruplet mutant the corresponding values
      for NADPH are >200 microM for K(m) and 2 min(-1) for k(cat) compared to 7.3
      microM and 7.2 min for the wild-type enzyme. By altering these four amino acids,
      the specificity constants for NADH and NADPH are almost exactly reversed in the
      mutant relative to the wild type.

PMID- 9015392
TI  - Purification of tyrosylprotein sulfotransferase from rat submandibular salivary
      glands.
AB  - Tyrosylprotein sulfotransferase (TPST), the enzyme responsible for the sulfation
      of tyrosine residues, has been identified and characterized in submandibular
      salivary glands. In the present study, this enzyme was purified from the Golgi
      membranes of rat submandibular salivary glands using a Cibacron blue F3GA
      affinity column chromatography. Antibodies raised in rabbit against TPST detected
      the purified enzyme (50-54 kDa) and proteins consisting of molecular mass 50-54
      kDa in the Golgi membranes of liver, submandibular salivary glands, stomach,
      cerebellum, thalamus, and pituitary. The protein levels in liver and salivary
      glands were higher compared to those found in the stomach, cerebellum, thalamus,
      and pituitary. The levels of immunoreactivity in cytosol and endoplasmic
      reticulum fractions of salivary glands were either undetectable or very low. The
      antibody was also used to immunoprecipitate the TPST activity and to isolate
      protein by immunoaffinity column. MnCl2 was required for the purified TPST. The
      enzyme exhibited optimum activity between pH 6.2 and 6.8 at 20 mM MnCl2. The
      apparent K(m) values of the purified enzyme for poly-(Glu6, Ala3, Tyr1) (EAY:
      M(r) 47,000) and 3'-phosphoadenosine 5'-phosphosulfate were 3 and 20 microM,
      respectively. The results presented here collectively demonstrate the
      purification of TPST and, for the first time, development of polyclonal antibody
      that recognizes this enzyme.

PMID- 9015393
TI  - Cyclic AMP regulation of mouse proline-rich protein gene expression:
      isoproterenol induction of AP-1 transcription factors in parotid glands.
AB  - Proline-rich protein mRNAs are increased dramatically in the salivary glands of
      rats, mice, and hamsters upon treatment with the beta-agonist isoproterenol.
      Sequence comparisons between mice and hamster proline-rich protein genes
      identified conserved regions upstream from the transcription start site. Reporter
      plasmids containing these 5'-flanking sequences from a mouse proline-rich protein
      gene, MP2, were constructed and tested for transcriptional regulation by cAMP.
      Transient transfection experiments in mouse L-M cells showed that the upstream
      region -702 to -322 bp relative to the transcription start site is sufficient to
      confer cAMP induction on a heterologous promoter. Multiple copies of the AP-1
      sequence elements within this region (-625 to -551) mediate the cAMP
      transcriptional response of reporter gene expression in L-M cells. L-M cell
      nuclear proteins and purified human c-jun protein bind to these upstream elements
      as determined by DNase I footprint analysis. Nuclear proteins isolated from mouse
      parotid glands protected the consensus AP-1 binding site 5'-TGAGTCA-3' (-592 to 
      586). The nuclear proteins interacting at this site were increased about sixfold
      in glands isolated from isoproterenol-treated mice when compared with glands from
      untreated mice. These results suggest that induction of AP-1 transcription
      factors in the parotid gland control the upregulation of some mouse salivary
      proline-rich proteins.

PMID- 9015394
TI  - Catalytic and structural importance of Gly-454, Tyr-455, and Leu-456 in the
      carboxy-terminal region of Escherichia coli F1-ATPase alpha subunit.
AB  - Monoclonal antibody alpha110 recognizes Leu-456 in the alpha subunit of the
      Escherichia coli F1-ATPase. Binding of this antibody to the alpha subunit or
      mutation of this residue to Pro caused enhancement of the ATPase activity,
      suggesting that this residue is involved in the catalytic mechanism of this
      molecule (H. Kanazawa et al. (1995) Arch. Biochem. Biophys. 317, 348-356). Leu
      456 together with Gly-454 and Tyr-455 are the only residues in the carboxy
      terminal 75 amino acids conserved among various species, suggesting that these
      three residues play important roles in catalysis by the ATPase. Here, we
      introduced site-directed mutations into these residues. Not only L456P but also
      G454L, Y455K, Y455L, and L456N mutations caused enhancement of the ATPase
      activity. Surprisingly, Y455V, L456H, and L456S caused assembly defects of F1
      subunits on the membrane. Reconstitution of the alpha betagamma complex from the
      wild-type beta and gamma subunits with the mutant alpha subunit (L4gamma6P)
      exhibited enhanced ATPase activity. Addition of delta or epsilon fused to
      glutathione S-transferase which are functionally similar to the delta and epsilon
      subunits, respectively, to the reconstituted F1-ATPase did not cause significant
      enhancement of its activity. Decreased interaction between alpha and beta
      subunits with the L456P mutation was detected by the yeast two-hybrid system.
      According to the deduced three-dimensional structure of the bovine a subunit, Leu
      456, Gly-454, and Tyr-455 are included in a small alpha helix. These results
      suggest that this alpha helix affects interaction of the alpha subunit with the
      beta subunit but not with delta or epsilon, which may be important for the
      catalytic mechanism and F1 assembly.

PMID- 9015395
TI  - Differential expression of the murine eukaryotic translation initiation factor
      isogenes eIF4A(I) and eIF4A(II) is dependent upon cellular growth status.
AB  - The murine translation initiation factor eIF4A is encoded by two genes: eIF4A(I),
      expressed in all mouse tissues, and eIF4A(II), a gene preferentially expressed in
      organs with low proliferative capacity. To investigate the hypothesis that
      regulation of the eIF4A isogenes is dependent upon cellular growth status, steady
      state expression of eIF4A(I) and eIF4A(II) mRNAs was quantitated in asynchronous
      cell populations and in cultures synchronized by nutrient starvation. Our data
      showed that changes in cell growth state were responsible for striking
      differences in eIF4A isogene-specific regulation. eIF4A(I) mRNA was 10-fold more
      abundant than eIF4A(II) in growing cells. In growth arrested cells eIF4A(I) mRNA
      levels remained unchanged, whereas eIF4A(II) mRNA levels increased approximately
      3-fold. Following serum stimulation of growth arrested cells, eIF4A(I) mRNA
      levels increased 3- to 10-fold; conversely, eIF4A(II) mRNA levels decreased 2- to
      3-fold. Thus, eIF4A(I) mRNA is synthesized and translated most efficiently in
      growing cells while eIF4A(II) mRNA synthesis and translation is associated
      preferentially with the growth-arrested (quiescent) state. This difference in
      expression patterns likely enables the cell to maintain required levels of this
      factor throughout its life cycle.

PMID- 9015397
TI  - Biophysical Society 41st annual meeting. New Orleans, Louisiana, 2-6 March 1997.
      Abstracts.

PMID- 9015396
TI  - Effect of trivalent metal ions on phase separation and membrane lipid packing:
      role in lipid peroxidation.
AB  - The capacity of Al3+-related cations (Sc3+, Ga3+, In3+, Be2+, Y3+, and La3+) to
      promote membrane rigidification and lateral phase separation was evaluated in
      liposomes containing zwitterionic (phosphatidylcholine, PC) and negatively
      charged (phosphatidylserine, PS) phospholipids. These effects were correlated
      with the capacity of the ions to stimulate Fe2+-supported lipid peroxidation.
      A13+, Sc3+, Ga3+, In3+, Be2+, Y3+, and La3+ (50-200 microM) increased the order
      parameter of the fluorescent probe 1,3-diphenylhexatriene incorporated in PC:PS
      membranes. In addition, the electron paramagnetic resonance spectra of spin
      labeled fatty acids indicated a reduction in lipid motion induced by Sc3+, Y3+,
      and La3+. The effect was found to extend down to carbon 16 on the acyl chain. The
      ions (10-200 microM) were also able to induce lateral phase separation, as
      evaluated from the increase in fluorescence quenching of the probe 2-(6-(7
      nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl-1-hexadec anoyl-sn-glycero-3
      phosphocholine. The ability of the ions to alter membrane lipid packing and
      induce lateral phase separation correlated in a positive manner (r2 = 0.91 and
      0.90, respectively) with their capacity to stimulate the production of Fe2+
      initiated 2-thiobarbituric-reactive species, a measure of lipid peroxidation.
      These results show that Al3+-related metal ions cause membrane rigidification and
      phase separation, which could affect membrane-related processes. The results
      support the hypothesis that ions without redox capacity can stimulate Fe2+
      initiated lipid peroxidation by increasing lipid packing and by promoting the
      formation of rigid clusters. Both processes will bring phospholipid acyl chains
      closer together, thus favoring the propagation step of lipid peroxidation.

PMID- 9015398
TI  - ISSOL'96. International Society for the Study of the Origin of Life. July 1996,
      Orleans, France. Abstracts.

PMID- 9015399
TI  - Swedish Association of Urology annual meeting. Stockholm, November 28-29, 1996.
      Abstracts.

PMID- 9015400
TI  - Vascular effects of loop diuretics.
AB  - Although it is generally believed that the beneficial effect of loop diuretics is
      the result of a rapid increase in diuresis, substantial evidence, from a large
      number of in vitro and in vivo experiments, has accumulated showing that
      administration of furosemide causes direct vascular effects, which probably
      contribute to its acute clinical effects. Several mechanisms are involved in the
      vascular response to loop diuretics. The role of the renin-angiotensin
      adolsterone axis, prostaglandins and the direct vascular effects of loop
      diuretics on both the arterial and venous parts of the vasculature are discussed.

PMID- 9015401
TI  - Oh my aching heart: a case for I.D.P. gene.

PMID- 9015402
TI  - Molecular biology and genetics of the angiotensin-I-converting enzyme: potential
      implications in cardiovascular diseases.

PMID- 9015403
TI  - Long-chain triglycerides improve recovery from myocardial stunning in conscious
      dogs.
AB  - OBJECTIVES: Free fatty acid (FFA) oxidation is depressed in the postischaemic
      stunned myocardium and recovers in parallel with the normalization of contractile
      performance. Assuming a causal role for this metabolic disturbance in the
      pathogenesis of stunning, we questioned whether exogenous administration of high
      dose triglycerides during reperfusion of postischaemic myocardium, could improve
      its functional recovery. METHODS: Thirteen dogs were chronically instrumented to
      measure global and regional haemodynamics and to produce a 10 min episode of
      regional myocardial ischaemia. In 7 dogs, Intralipid 20% was administered i.v.
      during the reperfusion phase. Contractile recovery of stunned myocardium was
      compared with control saline treatments. The series were repeated in another 6
      animals, but oxfenicine (CPT I inhibitor) preceeded Intralipid during
      reperfusion. RESULTS: Contractile recovery of stunned myocardium was faster and
      more extensive when Intralipid was administered during reperfusion than with
      saline treatment (wall thickening fraction 86 +/- 6% of preischaemic controls
      versus 52 +/- 11% at 90 min post-reperfusion; P < 0.05). Oxfenicine pretreatment
      completely abolished this beneficial effect. CONCLUSIONS: Exogenous
      administration of triglycerides during reperfusion of postischaemic myocardium
      improves functional recovery from stunning. This beneficial effect most likely
      operates through enhanced FFA availability and/or oxidation since it could be
      abolished by selective inhibition of the carnitine palmitoyl I enzyme.

PMID- 9015404
TI  - Inhibition of glyceraldehyde-3-phosphate dehydrogenase in post-ischaemic
      myocardium.
AB  - OBJECTIVE: Myocardial reperfusion following brief period of ischaemic is
      associated with prolonged, reversible periods of metabolic dysfunction. As the
      glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is inhibited
      in vitro by reactive oxygen species, we hypothesized that production of reactive
      oxygen species during reperfusion would lead to inhibition of GAPDH in post
      ischaemic myocardium. METHODS: Anaesthetized closed-chest-dogs were subjected to
      20 min balloon occlusion of the left anterior descending coronary artery. Biopsy
      samples were taken after 3 and 24 h of reperfusion, to determine the activity of
      GAPDH and the concentrations of glycolytic intermediates in post-ischaemic and
      remote, non-ischaemic territories. RESULTS: A significant reduction in GAPDH
      activity was observed in post-ischaemic relative to remote tissue after 3 h
      reperfusion (4.8 +/- 0.5 vs. 2.9 +/- 0.2 mumol/min/mg protein; P < 0.01). Western
      blotting revealed no reduction in the levels of GAPDH protein. Analysis of enzyme
      kinetics showed the loss of activity to be associated with decreased Vmax (5.9 +/
      0.5 vs. 3.2 +/- 0.2 mumol/min/mg protein; P < 0.01) with no significant change
      in the Km for glyceraldehyde-3-phosphate (GAP). Incubation of the inhibited
      enzyme under both mild and strong reducing conditions failed to reactivate the
      enzyme. The acute reduction in enzyme activity in post-ischaemic tissue was
      accompanied by regional differences in glycolytic intermediates, notably a
      twofold accumulation of GAP (P < 0.05), and a reduction in the glucose metabolic
      rate (GMR) determined by positron emission tomography and [18F]2
      fluorodeoxyglucose. By 24 h reperfusion, no regional differences in GAPDH
      activity, reaction Vmax or Km, GAP concentrations or GMR were detectable.
      CONCLUSIONS: These results suggest that inhibition of GAPDH activity may
      represent an important point at which glycolysis is limited during reperfusion,
      and further, that the mechanisms of enzyme inhibition do not involve simple
      oxidation or S-thiolation of critical active site thiol groups.

PMID- 9015405
TI  - Low-dose inotropic stimulation during left ventricular ischaemia does not worsen
      post-ischaemic dysfunction.
AB  - OBJECTIVE: Inotropic agents are used clinically to improve ventricular function
      during ischaemia. The goal of this study was to determine whether inotropic
      stimulation during moderate left ventricular (LV) ischaemia exacerbated post
      ischaemic LV dysfunction. METHODS: In 18 open-chest, anesthetized pigs, LV
      pressure versus subendocardial segment length loops were used to generate
      regional preload-recruitable stroke work (PRSW) and LV end-diastolic pressure
      (EDP) versus end-diastolic segment length (EDL) relations. Ischaemia was produced
      by constant, partial constriction of the mid anterior descending coronary artery
      for 90 min. Nine pigs received dobutamine (4 micrograms.kg-1.min-1, i.v.) during
      the final 60 min of ischaemia (Group 2), while 9 other pigs did not (Group 1).
      RESULTS: During unstimulated ischaemia, anterior subendocardial blood flow (Group
      1, 0.27 +/- .05; Group 2, 0.30 +/- .07 ml.g-1.min.-1, mean +/- s.e.m.) and steady
      state PRSW (Group 1, 30 +/- 4%; Group 2, 27 +/- 5% of baseline) were similar in
      both groups. Dobutamine stimulation during ischaemia increased heart rate, mean
      arterial pressure, subendocardial blood flow, oxygen consumption and steady-state
      PRSW of the ischaemia zone, but not lactate release. After 60 min reperfusion,
      steady-state ischaemic zone PRSW remained markedly and nearly equally reduced in
      both groups (Group 1, 28 +/- 4%; Group 2, 23 +/- 5% of baseline). Reduced PRSW
      after reperfusion was due primarily to persistent rightward shift of the PRSW
      intercept with only a modest contribution from reduced PRSW slope. CONCLUSIONS:
      Low-dose inotropic stimulation during moderate regional LV ischaemia increases
      aerobic, but not anaerobic energy metabolism, and does not worsen post-ischaemic
      dysfunction.

PMID- 9015406
TI  - Force pattern of hypoxic myocardium applied to oxygenated muscle preparations:
      comparison with effects of regional ischemia on the contraction of non-ischemic
      myocardium.
AB  - OBJECTIVE: To examine the basis for local wall motion abnormalities commonly seen
      in patients with ischemic heart disease, computer-controlled isolated muscle
      studies were carried out. METHODS: Force patterns of physiologically sequenced
      contractions (PSCs) from rat left ventricular muscle preparations under well
      oxygenated conditions and during periods of hypoxia and reoxygenation were
      recorded and stored in a computer. Force patterns of hypoxic-reoxygenating and
      oxygenated myocardium were applied to oxygenated and hypoxic-reoxygenating
      myocardium, respectively. RESULTS: Observed patterns of shortening and
      lengthening closely resemble those obtained from ischemic and non-ischemic
      myocardial segments using ultrasonic crystals in intact dog hearts during
      coronary occlusion and reperfusion, and are similar to findings reported in
      angiographic studies of humans with coronary artery disease. CONCLUSION: The
      current study, demonstrating motions of oxygenated isolated muscle preparations
      which are similar to those in perfused segments of intact hearts with regional
      ischemia, supports the concept that the multiple motions of both ischemic and non
      ischemic segments seen in regional myocardial disease can be explained by
      interactions of strongly and weakly contracting muscle during the physiologic
      cardiac cycle.

PMID- 9015407
TI  - Modulation of myocardial economy and efficiency in mammalian failing and non
      failing myocardium by calcium channel activation and beta-adrenergic stimulation.
AB  - OBJECTIVE: We investigated the energy-metabolic consequences of positive
      inotropic stimulation by the calcium channel activator, BAY K 8644, in comparison
      with isoprenaline, focussing both on the economy of force development and the
      efficiency of external work. METHODS: In the first instance, heat liberation was
      measured in isometrically contracting right ventricular papillary muscles from
      guinea pigs by means of antimony-bismuth thermopiles; in the second instance,
      external work and myocardial oxygen consumption were analyzed in isolated failing
      and non-failing working rat hearts. RESULTS: In the guinea pig muscle strip
      preparations BAY K 8644 (10(-5) M) and isoprenaline (10(-8 M) increased peak
      developed force from 13.7 +/- 2.7 to 37.6 +/- 14.9 mN/mm2 and from 13.6 +/- 5.2
      to 38.8 +/- 3.3 mN/mm2, respectively (P < 0.01). Stress-time integral was
      increased from 10.3 +/- 3.0 to 34.7 +/- 19.2 mN.s/mm2 by BAY K 8644 and from 9.5
      +/- 2.4 to 23.0 +/- 1.6 mN.s/mm2 by isoprenaline. Whereas a significant decrease
      in the ratio between stress-time integral and initial heat (integral of Pdt/IH)
      (i.e., economy contraction) was observed for isoprenaline (5.26 +/- 1.91 before
      and 3.11 +/- 0.72 N.m.s.J-1 after treatment (P < 0.01), BAY K 8644 did not
      significantly alter this index (5.26 +/- 2.39 before and 6.22 +/- 2.63 N.m.s.J-1
      after treatment). Similar results were obtained for the ratio between stress-time
      integral and tension-dependent heat. Significantly more calcium ions were
      required for equieffective activation of the contractile proteins with
      isoprenaline as compared to BAY K 8644. In working preparations of sham-operated
      and infarcted rat hearts, the increase in myocardial oxygen consumption per
      minute (delta MVO2) for a given increase in external work per minute (delta P)
      was significantly higher with isoprenaline than with equipotent concentrations of
      BAY K 8644 or high calcium. CONCLUSIONS: Inotropic mycardial stimulation by BAY K
      8644 is associated with higher economy and efficiency than stimulation by
      isoprenaline when analyzed both by heat measurements in isometric preparations
      and by myocardial oxygen consumption in working heart preparations.

PMID- 9015408
TI  - Direct evidence that ischemic preconditioning does not cause protein kinase C
      translocation in rabbit heart.
AB  - OBJECTIVE: Indirect pharmacological evidence suggests that myocardial protection
      conferred by ischemic preconditioning in rabbit myocardium is mediated through
      the translocation of protein kinase C (PKC). To test this hypothesis, we
      performed direct biochemical measurements of subcellular distribution of PKC in
      rabbit hearts. METHODS: Two protocols were utilized. In Protocol I the
      preconditioned group (PC) underwent two 5-min episodes of brief coronary artery
      occlusion each followed by 5 min of reperfusion, while the control group
      consisted of time-matched, sham-operated (non-ischemic) animals (SO). Tissue
      samples were homogenized and cytosolic and particulate fractions were obtained by
      ultracentrifugation. In Protocol II one group of rabbits received ischemic
      preconditioning as in Protocol I followed by 10 min of sustained ischemia (PC +
      IS); a second control group was subjected to 10 min of sustained ischemia (IS);
      and the third group was time-matched, sham-operated (non-ischemic) animals (SO).
      Homogenized tissue samples were separated into cytosolic, nuclear and membrane
      fractions. RESULTS: In Protocol I, no differences in the subcellular distribution
      of PKC between the SO and PC groups were observed. In Protocol II, when samples
      were obtained at 10 min of sustained ischemia, no changes in the subcellular
      distribution of PKC were observed between SO, IS and PC + IS groups. CONCLUSION:
      Our results indicate that translocation of protein kinase C is not an important
      mediator of ischemic preconditioning in the rabbit ischemia model.

PMID- 9015409
TI  - Myocardial ischemia/reperfusion protection using monophosphoryl lipid A is
      abrogated by the ATP-sensitive potassium channel blocker, glibenclamide.
AB  - OBJECTIVES: Monophosphoryl lipid A (MLA), a detoxified derivative of the lipid A
      portion of the endotoxin molecule, given as a pretreatment 24 h prior to cardiac
      ischemia/reperfusion reduces myocardial stunning and infarction in dogs. This
      study was undertaken to evaluate the ability of MLA pretreatment to reduce
      infarct size in a rabbit model of in situ regional myocardial ischemia and
      reperfusion. Secondly, the potential role of modulation of ATP-sensitive
      potassium (KATP) channel in MLA's cardioprotection was evaluated using in vivo
      pharmacologic antagonism with a KATP channel blocker, as was the role of tumor
      necrosis factor using an enzyme-linked immunosorbent assay method of serum
      cytokine analysis. METHODS: Rabbits were pretreated intravenously with MLA or
      vehicle injection 24 h prior to initiation of 30 min in situ left anterior
      descending coronary artery occlusion followed by 3 h reperfusion. In animals
      receiving glibenclamide, the potassium channel antagonist was administered 30 min
      prior to inducing ischemia. Animals receiving glibenclamide, which possesses
      hypoglycemic effects, underwent serial blood glucose evaluation prior to drug and
      throughout the ischemia and reperfusion periods. Hemodynamics were monitored;
      infarct size and area at risk were assessed by contrast dye staining
      (triphenyltetrazolium chloride). Serum tumor necrosis factor was measured by
      enzyme-linked immunosorbent method in animals administered cardioprotective doses
      of MLA as well as pyrogenic doses of MLA and endotoxin (positive control) to
      determine if elaboration of this cytokine could be associated with the
      cardioprotective effect of MLA. RESULTS: MLA administered as a single intravenous
      dose 24 h prior to ischemia reduced infarct size, expressed as a percent of the
      area at risk, 64 and 71% at doses of 35 and 10 micrograms/kg, respectively. Lower
      doses of MLA (2.5 and 5 micrograms/kg) did not significantly reduce infarct size.
      Administration of glibenclamide (300 micrograms/kg) 30 min prior to ischemia
      completely blocked the ability of MLA pretreatment to limit infarct size, while
      MLA vehicle-glibenclamide-treated control rabbits displayed infarcts not
      significantly different from MLA-vehicle-treated control rabbits. A
      cardioprotective dose of MLA (35 micrograms/kg) did not induce the elaboration of
      tumor necrosis factor into rabbit serum (within the limits of assay sensitivity).
      CONCLUSIONS: Single-dose pretreatment with MLA administered intravenously to
      rabbits substantially reduces infarct size when administered 24 h prior to
      ischemia. Pharmacologic preconditioning with MLA appears to be mediated through
      KATP channels as the channel blocker, glibenclamide, reversed the
      cardioprotective activity of MLA when administered 1 day following MLA
      pretreatment, yet 30 min prior to ischemia. In this model the cardioprotective
      does not appear to be associated with increases in serum tumor necrosis factor.

PMID- 9015411
TI  - Determinants of coronary reserve in rats subjected to coronary artery ligation or
      aortic banding.
AB  - OBJECTIVE: We investigated whether decreased coronary reserve in hearts after
      coronary artery ligation or in hearts from rats after aortic banding can be
      related to remodeling of resistance arteries. METHODS: Maximal coronary flow
      (absolute flow) and cardiac perfusion (flow corrected for heart weight) were
      determined in isolated, perfused rat hearts after adenosine or nitroprusside, at
      3 and 8 weeks after coronary artery ligation or 4-5 weeks after aortic banding.
      Perivascular collagen and medial thickness of resistance arteries were determined
      by morphometry. RESULTS: maximal coronary flow of infarcted hearts had been
      restored to sham values at 3 weeks. Growth of cardiac muscle mass from 3 to 8
      weeks exceeded the increase in maximal coronary flow, leading to a decreased
      perfusion at 8 weeks. A slight, transient increase in perivascular collagen, but
      no medial hypertrophy, was found after infarction. After aortic banding
      perivascular fibrosis and medial hypertrophy led to a decreased maximal coronary
      flow in both the hypertrophied left and the non-hypertrophied right ventricle.
      Consequently, perfusion of the left ventricle was most severely reduced.
      CONCLUSIONS: Reduced maximal perfusion after aortic banding is determined by both
      cardiac hypertrophy and vascular remodeling. In contrast, during infarction
      induced remodeling, reduction of perfusion is not determined by vascular
      remodeling, but mainly by disproportional cardiac hypertrophy relative to
      vascular growth.

PMID- 9015410
TI  - Effect of ischaemic preconditioning on vascular dysfunction induced by ischaemia
      and reperfusion in rat hindquarters.
AB  - OBJECTIVE: The aim of this study was to examine the effect of ischaemia on
      vascular responses to endothelium-dependent and endothelium-independent
      vasodilators and on vasoconstrictor responses. Furthermore, the ability of
      preconditioning to prevent ischaemia-induced changes in vascular reactivity was
      examined in the rat hindquarters. METHODS: The abdominal aortae of anaesthetized
      rats were cannulated for hindquarters perfusion with Krebs bicarbonate solution
      containing phenylephrine to induce vasoconstrictor tone. Responses of the
      hindquarters to endothelium-dependent and endothelium-independent vasodilators
      were examined. Hindquarters responses to neuronal release of the vasodilator
      acetylcholine (ACh) induced by peri-aortic nerve stimulation were also examined.
      RESULTS: Ischaemia with 2 h aortic occlusion prior to Krebs perfusion attenuated
      vasodilator responses to the neuronal release of ACh [10 Hz; decrease in
      perfusion pressure (delta PP) control: -18(s.e.m. 3) mmHg, Ischaemic: -13(3)
      mmHg], exogenous ACh [10 ng; delta PP control: -22(2) mmHg, ischaemic: -17(2)
      mmHg] and carbachol [1.0 micrograms; delta PP control: -21(3) mmHg, ischaemic: 
      12(3) mmHg]. Responses to other endothelium-dependent vasodilators bradykinin and
      histamine or the endothelium-independent vasodilator, sodium nitroprusside, were
      not impaired by ischaemia. Similarly vasoconstriction to noradrenaline and
      serotonin was not affected. Ischaemia preceded by preconditioning with 5 min
      aortic occlusion and 10 min reperfusion prevented impairment of vasodilatation to
      nerve stimulation [1.0 micrograms; delta PP preconditioned: -24 (3)
      preconditioned: -20(1) mmHg], ACh [10 ng; delta PP preconditioned: -22(1) mmHG]
      and carbachol [1.0 micrograms; delta PP preconditioned: -24(3) mmHG]caused by
      ischaemia. CONCLUSIONS: These data indicate that hindquarters ischaemia causes
      selective impairment of dilator responses to muscarinic agonists and ischaemic
      preconditioning prevents that impairment.

PMID- 9015412
TI  - Inflammatory cells and myocardial fibrosis: spatial and temporal distribution in
      renovascular hypertensive rats.
AB  - OBJECTIVE: The fibroblasts producing collagen are co-localized with inflammatory
      cells in myocardial fibrosis areas of spontaneously hypertensive rats, suggesting
      that collagen overproduction in this model may be modulated by inflammatory
      cells. The present study extends these observations to the Goldblatt model of
      hypertension in which the renin-angiotensin system is activated. METHODS:
      Inflammatory cells were identified with monoclonal antibodies directed against
      macrophages (ED1+), T helper (CD4+) and cytotoxic lymphocytes (CD8+), and MHC
      class II-expressing cells (Ia+). The alkaline phosphatase-anti-alkaline
      phosphatase (APAAP) immuno-staining technique was used. A new computer-assisted
      morphometric method was utilized to quantify the inflammatory infiltrate in each
      cardiac compartment with polarized-light microscopy. Cells responsible for the
      collagen synthesis were identified by in situ hybridization. The collagen content
      was estimated by morphometry on left ventricle sections stained with Sirius red,
      and by biochemical quantification of the hydroxyproline concentration. RESULTS:
      Computer-assisted morphometry under polarized light was well suited to quantify
      inflammatory cells labeled by the APAAP technique. Inflammatory cells were co
      localized with collagen-synthesizing fibroblasts. The main inflammatory cells
      were CD4+ lymphocytes > Ia+ > ED1+ > CD8+ cells. These cell densities were
      increased in hypertensive rats in all cardiac areas compared to control rats
      except for IA+ cells which were concentrated in microscars. Macrophage density
      was correlated with plasma renin activity. The inflammatory cell density which
      best correlated with fibrosis was macrophage density, and which best correlated
      with systolic blood pressure was macrophage and T helper lymphocyte densities.
      CONCLUSIONS: One can speculate that the correlation between macrophage density
      and blood pressure as well as with plasma renin activity may indicate that
      angiotensins and/or elevation of blood pressure could participate in the initial
      signalling which may mobilize inflammatory cells. These inflammatory cells could
      promote fibrosis by releasing mediators such as growth factors or cytokines which
      act upon fibroblasts.

PMID- 9015413
TI  - Altered resistive vessel function after coronary angioplasty is not due to
      reduced production of nitric oxide.
AB  - BACKGROUND: The coronary vasodilator reserve with dipyridamole may be impaired
      immediately after successful angioplasty due to reduced endothelial production or
      release of nitric oxide. As the vasodilator response to exogenous nitrates is
      enhanced by endothelium removal or inhibition of nitric oxide synthesis, an
      increased vasodilator response to nitrovasodilators, such as nitroprusside,
      should occur. METHODS: The coronary vasodilator reserve (maximal/basel coronary
      blood flow) with intravenous dipyridamole (0.56 mg/min for 4 min) was measured by
      Doppler catheterization before and after angioplasty in 10 patients with single
      vessel coronary disease. At peak dipyridamole effect, incremental doses of
      nitroprusside (4-50 micrograms/min) were given intracoronary until systolic blood
      pressure fell by > or = 5 mmHg. RESULTS: Before angioplasty, the coronary blood
      flow increased from 19.7 +/- 6.1 (mean +/- s.d.) at basal to 30.1 +/- 11.9 ml/min
      at the peak dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve
      of 1.62 +/- 0.39 (range 1.20 - 1.96). After angioplasty, the coronary blood flow
      increased from 32.4 +/- 13.2 at basal to 53.4 +/- 23.3 ml/min at the peak
      dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve of 1.77 +/-
      0.64 (range 1.7-2.42). Sodium nitroprusside had no additional effect on coronary
      flow (49.5 +/- 20.4 and 52.2 +/- 18.0 ml/min) before and after a fall in systolic
      blood pressure, respectively. CONCLUSIONS: The vasodilator response to
      dipyridamole was markedly impaired immediately after successful angioplasty, and
      was not augmented by intracoronary nitroprusside. Thus, a reduced production or
      release of nitric oxide in the coronary circulation does not seem to be
      responsible for the impaired vasodilator response after angioplasty.

PMID- 9015414
TI  - Whey mineral supplementation and arterial tone in mineralocorticoid-NaCl
      hypertension.
AB  - OBJECTIVE: The aim was to study the effects of supplementation of rat chow diet
      with whey mineral concentrate (Whey), a diet rich in milk minerals, on arterial
      responses in vitro in mineralocorticoid-NaCl hypertension. METHODS: Forty young
      Wistar rats were allocated to four groups: Wistar, Whey-Wistar,
      deoxycorticosterone (DOC), and Whey-DOC. DOC (10 mg kg-1 s.c.) was given twice a
      week and these rats drank 0.7% NaCl solution, while the others received equal
      volumes of vehicle (sesame oil) and drank tap water. The supplementation was
      performed by adding 25% whey mineral concentrate to the chow, which in particular
      increased the intake of potassium and also that of calcium and magnesium in the
      rats. Responses of mesenteric arterial rings were examined in standard organ
      chambers after 10 study weeks. RESULTS: During the 10 week study the DOC-NaCl
      treatment had a marked hypertensive effect in rats, while the whey mineral
      supplementation was without significant effect on blood pressure in the Whey-DOC
      and Whey-Wistar groups. Arterial relaxation induced by nitroprusside was
      attenuated in the DOC-treated rats, but was significantly shifted towards that of
      controls in the Whey-DOC group. Interestingly, endothelium-dependent relaxation
      to acetylcholine (ACh), which was clearly impaired in the DOC group, was
      comparable in the Whey-DOC and Wistar groups. Moreover, only in the DOC group the
      relaxation was improved by diclofenac suggesting that ACh was releasing cyclo
      oxygenase-derived contractile factors from the endothelium, and the response was
      completely abolished by NG-nitro-L-arginine methyl ester (L-NAME). In contrast,
      diclofenac had a negligible effect on the response in the other groups which also
      showed distinct relaxations to ACh in the presence of L-NAME. This remaining
      response to ACh in Wistar rats was inhibited by the addition of apamin and
      glibenclamide, inhibitors of calcium-activated and ATP-sensitive potassium
      channels, respectively, suggesting that it was mediated by endothelium-dependent
      hyperpolarization. In the Whey-Wistar group arterial function did not differ from
      control Wistars. CONCLUSIONS: Supplementation with whey mineral concentrate had a
      protective effect on endothelium-mediated control of arterial tone in
      experimental DOC-NaCl hypertension.

PMID- 9015415
TI  - Synthesis of TNF alpha and TGF beta mRNA in the different micro-environments
      within atheromatous plaques.
AB  - OBJECTIVE: To examine localisation of tumour necrosis factor (TNF alpha) and
      transforming growth factor beta (TGF beta) mRNA synthesis in human coronary
      artery atheromatous plaques, to explore how synthesis of these cytokines relates
      to distribution of macrophages and smooth muscle cells, and to correlate this
      with plaque micro-environments. METHOD: In situ hybridisation with digoxigenin
      labelled sense and anti-sense riboprobes was used, combined with
      immunohistochemistry to detect TNF alpha protein, macrophage, lymphocyte and
      smooth muscle cell markers. RESULTS: In the intimal plaque TNF alpha mRNA is
      synthesised by monocytes/macrophages as well as by smooth muscle cells. Both TNF
      alpha and TGF beta mRNAs were present at the margins of the lesions and in
      reactive areas, where there was little lipid and fibrosis. Focal aggregates of
      macrophages in the adventitia expressed both TNF alpha mRNA and protein and TGF
      beta mRNA. CONCLUSION: Synthesis of these two cytokines by macrophages as well as
      smooth muscle cells contributes to the pathobiology of the plaque and that this
      is part of the 'reaction to injury', rather than a feature of a specific cell, or
      a specific layer, within the vessel wall.

PMID- 9015417
TI  - Additional elevation of the ST segment: a possible early electrocardiographic
      marker of experimental myocardial reperfusion.
AB  - OBJECTIVE: To analyze the early electrocardiographic changes during experimental
      coronary reperfusion after 1 to 4 h of coronary occlusion. METHODS: Recordings of
      epicardial and endocardial DC electrograms were performed in 35 open-chest pigs
      during coronary occlusions of 1 to 4 h duration followed by 1 h of reperfusion.
      RESULTS: During occlusion, maximal ST segment elevation was reached between min
      10 and 30 which was followed by and a steady decline. During the first 30 min of
      reperfusion, however, there was a further elevation of the ST segment with a peak
      at 5 min. Thus, values at the end of occlusion and at 5 min of reperfusion were:
      (a) group with 1 h occlusion (n = 11), 15.5 +/- 7 and 37.4 +/- 11.4 mm, P <
      0.005; (b) group with 2 h occlusion (n = 6), 10.2 +/- 4 and 24.7 +/- 9.4 mm, P <
      0.03; (c) group with 3 h occlusion (n = 6), 7.5 +/- 3 and 16.8 +/- 5.6 mm, P <
      0.03; and (d) group with 4 h occlusion (n = 12), 6.4 +/- 2.4 and 17.0 +/- 8.9 mm,
      P < 0.01. In 9 animals from the group with 1 h occlusion, a second cycle of 1 h
      occlusion and reperfusion also showed re-elevation of ST segment during
      reperfusion, although to a lesser extent than the first one (from 10.0 +/- 4.9 to
      16.3 +/- 7.1 mm, P < 0.01). CONCLUSIONS: Thus, our findings provide experimental
      evidence of an additional and paradoxical ST segment elevation as the earliest
      electrocardiographic sign of coronary reperfusion after 1 to 4 h of coronary
      occlusion. These observations may help to improve the interpretation of early
      electrocardiographic changes during thrombolysis in acute myocardial infarction.

PMID- 9015416
TI  - Tyrosine kinase inhibitor suppresses the (re) stenotic changes of the coronary
      artery after balloon injury in pigs.
AB  - OBJECTIVE: Restenosis after percutaneous transluminal coronary angioplasty (PTCA)
      still remains a serious late complication. Many growth factors induced in
      restenotic lesions may be responsible for restenosis after PTCA. Most of the
      receptors for such growth factors possess tyrosine kinase activity. This study
      was designed to determine whether or not a specific tyrosine kinase inhibitor, ST
      638, can prevent (re)stenotic changes of the coronary artery after balloon
      injury. METHODS: A segment of the porcine coronary artery was aseptically wrapped
      with cotton mesh absorbing either ST 638 or vehicle, followed by balloon injury.
      Two weeks after the procedure, coronary stenosis and vasoconstricting responses
      were examined by coronary arteriography and (re)stenotic changes of the coronary
      artery were histologically examined. Antiphosphotyrosine immunoblotting was also
      performed to examine the inhibitory effects of ST 638. RESULTS: Coronary
      arteriography showed the development of mild stenotic lesions at the balloon
      injured sites, where hyperconstrictive responses were repeatedly induced by
      intracoronary serotonin and histamine. Histologically, neointimal formation was
      noted at the balloon-injured site, where the total vessel area also tended to
      decrease (geometric remodeling). The treatment with ST 638 suppressed all the
      hyperconstrictive responses, the neointimal formation, and the geometric
      remodeling induced by balloon injury. Immunoblotting for phosphotyrosine proteins
      demonstrated the elevation of proteins at the balloon-injured site, which was
      suppressed by ST 638. CONCLUSIONS: These results indicate that tyrosine kinases
      are activated at the balloon-injured site and the inhibition of such kinase
      activities is effective in reducing both the (re)stenotic changes (neointimal
      formation and geometric remodeling) and the hyperconstrictive responses of the
      coronary artery after balloon injury.

PMID- 9015419
TI  - Large vestibular aqueduct: large endolymphatic sac?

PMID- 9015418
TI  - Plasma endothelin in congestive heart failure: effect of the ACE inhibitor,
      fosinopril.
AB  - OBJECTIVES: The study evaluates the influence of treatment with the angiotensin
      converting enzyme inhibitor, fosinopril, on the plasma endothelin level in
      patients with congestive heart failure, and the relationship between plasma
      endothelin and clinical study parameters (bicycle exercise test,
      echocardiography, heart failure score and blood pressure). METHODS: Plasma
      endothelin was measured in 34 patients with moderately severe congestive heart
      failure at randomisation in the fosinopril/placebo-controlled study 'Fosinopril
      Efficacy and Safety Trial' and at the end of the 12-week study period. RESULTS:
      The patients had elevated pre-treatment plasma endothelin concentrations (3.5 +/-
      1.2 pg/ml, mean +/- s.d., n = 34) compared with healthy volunteers (2.0 +/- 0.4
      pg/ml, n = 21, P < 0.0001). Treatment with fosinopril for 12 weeks lowered plasma
      endothelin from 3.5 +/- 1.2 to 2.5 +/- 0.7 pg/ml (m = 18, P < 0.005), in contrast
      to the non-significant increase in the placebo-treated group 3.5 +/- 1.3 to 4.3
      +/- 2.4 pg/ml, n = 16). A multiple regression analysis for baseline study
      parameters, demonstrated a significant relationship between plasma endothelin and
      exercise test duration and a composite heart failure score classification (r =
      0.53, P < 0.001). CONCLUSIONS: Treatment of patients with congestive heart
      failure with the angiotensin-converting enzyme inhibitor, fosinopril, reduce the
      elevated plasma endothelin level to normal values. The relation between plasma
      endothelin and clinical parameters indicates that endothelin may play a
      pathophysiological role in the progression of congestive heart failure.

PMID- 9015420
TI  - The surgical treatment of snoring.

PMID- 9015421
TI  - Meniere's disease: evolution of a definition.
AB  - In 1861 Prosper Meniere separated patients with episodic vertigo, hearing loss
      and tinnitus from a group previously described as having apoplectiform cerebral
      congestion. He suggested the cause was disease within the semicircular canals
      (Meniere, 1861). Over the years it became apparent that within this group there
      were a number of patients with characteristic signs and symptoms and in 1938 a
      pathological correlate was found in the form of endolymphatic hydrops.
      Descriptions such as Meniere's 'disease', Meniere's 'syndrome' and Meniere's
      'symptom complex' led to a confusing array of terms for this condition and
      monitoring of treatment results became difficult. In response to this in 1972 the
      American Academy of Ophthalmology and Otolaryngology Committee on Hearing and
      Equilibrium published a clear definition of Meniere's disease and criteria for
      the reporting of treatment results, it was updated in 1985 and again in 1995. We
      describe the changes that have taken place as the definition of Meniere's disease
      has evolved.

PMID- 9015422
TI  - Estimation of otitis media in ancient populations. A study of past and present
      Greenlandic Inuit.
AB  - Examination of disease patterns in the past has often been difficult due to lack
      of morphological evidence. This study presents a new unbiased method for
      estimation of occurrence of infectious middle ear disease (IMED) in childhood.
      The method is based on the relation between IMED in childhood and small or
      asymmetric pneumatized cell areas in the temporal bones as seen on standardised X
      rays. A polychotomous logistic regression model was applied on 434 pneumatized
      cell areas in temporal bones from 34 adult living Greenlandic Inuit, 56 adult
      crania from the 18th to the 19th century, A.D. and 127 adult Inuit crania from
      the pre-European colonization period (before A.D. 1721) of Greenland. The
      occurrence of IMED as designated by the model was eight out of 34 (23.5 per cent)
      in living Inuit, 10 out of 56 (17.9 per cent) in crania from the 18th to 19th
      century and six out of 127 (4.7 per cent) in crania from the pre-colonization
      period. These frequencies differed significantly (p < 0.002). The mean area size
      also differed significantly, thus indicating a change in occurrence of IMED and a
      decrease in area sizes from past to present in Greenland.

PMID- 9015423
TI  - A clinical, genetic and audiological study of patients and families with
      unilateral vestibular schwannomas. II. Audiological findings in 93 patients with
      unilateral vestibular schwannomas.
AB  - Nine-three patients with histologically or radiologically confirmed unilateral
      vestibular schwannomas were recruited. Audiological testing for retrocochlear
      pathology was undertaken. Patients' hospital records were examined for previous
      audiological and radiological results. The audiometric configuration was
      designated as one of the following: normal, sloping, low frequency, peak, trough
      or flat. A sloping sensorineural audiometric configuration was present in 68 per
      cent of cases. No significant correlation was found between tumour size and
      average pure tone threshold 500 Hz to 4000 Hz, optimum discrimination score or
      interaural differences for wave V. Ninety-one per cent of cases had abnormalities
      on auditory evoked potential; 92 per cent of cases showed abnormalities on
      stapedial reflex testing. The limitations of audiological testing in the
      investigation of patients with suspected unilateral vestibular schwannomas are
      discussed. A protocol for the investigation of such patients is presented.

PMID- 9015424
TI  - A cost effective screening protocol for vestibular schwannoma in the late 90s.
AB  - Magnetic resonance imaging (MRI) is the imaging modality of choice in diagnosing
      vestibular schwannoma (VS). Perceived high costs have prevented clinicians from
      using it as a screening investigation, although MR scanners are now widely
      available in the United Kingdom. In a retrospective study, the clinical records
      of all the patients who presented to the ENT department of Taunton and Somerset
      NHS Trust with suspected symptoms of VS during the year 1994 were analysed. The
      cost of confirming or refuting the diagnosis of VS in each patient ranged from
      220.72 pounds to 580.31 pounds depending on the number of hospital visits and
      investigations performed. This study shows that the routine use of MR scanning
      for detection of VS is cost effective and more effective than the use of
      conventional tests.

PMID- 9015425
TI  - Nonspecific vertigo with normal otoneurological examination. The role of
      vestibular laboratory tests.
AB  - Vestibular laboratory tests are not generally necessary in the diagnosis of
      patients with a clear description of vertigo accompanied by positive
      otoneurological examination findings. The purpose of the study was to investigate
      the role of conventional vestibular laboratory tests in the diagnosis of patients
      complaining of nonspecific vertigo, despite their having a documented normal
      otoneurological examination. The results of the standard electronystagmography
      (ENG) and sinusoidal harmonic acceleration (SHA) tests of 52 patients referred
      for ambulatory vestibular laboratory tests due to a nonspecific illusion of
      movement, but with a normal otoneurological examination, were reviewed.
      Abnormalities were found in the vestibular tests of 35 patients (67 per cent), 22
      of whom (63 per cent) were finally diagnosed as having a unilateral peripheral
      vestibular lesion, and 13 (37 per cent) benign positional vertigo. These results
      suggest that a high percentage of patients with nonspecific vertigo and a normal
      otoneurological examination probably suffer from peripheral vestibular
      dysfunction, which can be objectively documented by the ENG and SHA tests.

PMID- 9015427
TI  - An in vitro study of tracheostomy tube cuff herniation and inflation
      characteristics.
AB  - Seven of the most commonly used tracheostomy tubes used in the UK were tested for
      cuff herniation and creasing in synthetic tracheas corresponding to the shapes
      and sizes found in vivo. Results demonstrated that only two tubes of one
      particular brand herniated and that creasing occurred in tubes disproportionately
      large for the trachea used. A discussion of modern tracheostomy tube manufacture
      is included.

PMID- 9015426
TI  - Vocal function following laser and conventional surgery of small malignant vocal
      fold tumours.
AB  - In the described study, 26 patients after conventional cordectomy, and 27
      patients after laser cordectomy were examined six months or more after the
      operation. Videolaryngostroboscopy revealed that patients after laser cordectomy
      more often phonate on purely glottic level (81 per cent) in comparison to
      patients after conventional cordectomy (19 per cent). Webs were more frequent and
      more extended after conventional cordectomy compared to endoscopic laser surgery.
      The maximal phonation time showed a very wide range with a mean value of 9 to 10
      sec; there was no statistical difference between the groups of patients. Using
      Yanagihara's classification of sonograms, a better voice quality was measured
      after laser cordectomy than conventional cordectomy. The patients' estimation of
      their voice quality did not correlate with objective parameters.

PMID- 9015428
TI  - Otological lesions in pachyonychia congenita syndrome.
AB  - The authors report a case of a patient with pachyonychia congenita syndrome, a
      rare genodermatosis inherited as an autosomal dominant trait, who also had
      otological lesions beyond the other classic signs and symptoms of the syndrome.
      Many kinds of treatment have already been proposed, but all failed to show
      satisfactory results. A new, cheap and easy-to-use treatment was developed in
      this study, using keratoplastics interpolated with humectant lotion for 90 days.
      The results after three years of follow-up are still thoroughly satisfactory.

PMID- 9015429
TI  - Sudden sensorineural deafness and hormone replacement therapy.
AB  - Whilst the oral contraceptive pill (OC) has been implicated on a number of
      occasions as a cause of sensorineural hearing loss, there are no published
      reports linking hormone replacement therapy (HRT) to otological symptoms. A case
      of sensorineural loss with tinnitus following commencement of HRT is described,
      followed by a discussion outlining the fundamental differences between the OC and
      HRT, thus explaining why a vascular aetiology is unlikely. It is hypothesized
      that otological symptoms in such cases may be due to the effect of oestrogens on
      electrolyte balance disturbing inner ear function and also a direct effect on the
      auditory pathways mediated in part by alterations in neurotransmitter receptor
      concentrations.

PMID- 9015430
TI  - Cochlear implantation in superficial siderosis.
AB  - Superficial siderosis is a rare central nervous system disorder characterized by
      deafness, ataxia, and pyramidal signs. The hearing loss is believed to be
      predominantly neural and is usually progressive and bilateral. Careful assessment
      is therefore necessary to determine the best approach to hearing rehabilitation.
      A case is presented of superficial siderosis in a young woman who has benefitted
      significantly from cochlear implantation using the Nucleus device.

PMID- 9015431
TI  - Rhinoentomophthoromycosis. Report of two cases.
AB  - Two cases of rhinoentomophthoromycosis are presented. This rare disease can
      produce progressive deformity of the nose and facial structures. A review of the
      clinical symptoms along with its diagnosis and treatment is described.

PMID- 9015432
TI  - Cystic lesions of the nasal cavity and the paranasal sinuses: report of two
      unusual cases.
AB  - The clinicopathological features of two unusual cystic lesions, one arising in
      the nose, a calcified mucocele or a calcified retention cyst and the other in the
      maxillary sinus, a dentigerous cyst originating in a supernumerary tooth, are
      described. The literature on these two rare lesions is briefly reviewed.

PMID- 9015433
TI  - Somatostatin receptor imaging of olfactory neuroblastoma.
AB  - Neural-crest tumours, including neuroblastomas, express somatostatin receptors.
      This can be shown by radionuclide labelling of octreotide, a somatostatin
      analogue. Studies on imaging with this substance have dealt with childhood
      neuroblastomas. Olfactory neuroblastoma (aesthesioneuroblastoma) is a rare tumour
      in which somatostatin receptor content has not been analysed, nor have
      radionuclide methods for diagnostic purposes been described. We report a case of
      olfactory neuroblastoma, in which scanning with 111In-labelled octreotide was
      performed. A strong uptake was seen at the base of the skull. This was confirmed
      as a recurrent tumour by magnetic resonance (MR) imaging. Uptake was also
      observed in the neck and chest, indicating extensive spread of the disease.
      Somatostatin receptor expression has been shown to correlate with prognosis in
      childhood neuroblastoma. The accuracy of labelled octreotide in the diagnosis of
      olfactory neuroblastoma indicates that it might be useful in radionuclide therapy
      of patients with advanced disease, when no other treatment modalities are
      available.

PMID- 9015434
TI  - An unusual foreign body in the larynx: a case report.
AB  - Inhalation of a foreign body is a serious event. A small proportion of foreign
      bodies become impacted in the larynx, when urgent recognition is required to
      prevent disaster. The case of an 18-month-old baby with an impacted artificial
      finger nail in the larynx is described along with a brief review of the
      literature.

PMID- 9015435
TI  - Spontaneous internal jugular vein thrombosis and recurrent laryngeal nerve palsy:
      a rare simultaneous presentation of an occult malignant neoplasm.
AB  - Internal jugular vein thrombosis is an uncommon potentially life-threatening
      disorder caused by various conditions. Non-spontaneous internal jugular vein
      thrombosis is an uncommon condition associated in the pre-antibiotic area with
      deep-neck infections. Currently iatrogenic trauma to the internal jugular vein
      from catheterisation and repeated intravenous injections by drug abusers are the
      leading causes of thrombosis. Spontaneous internal jugular vein thrombosis may
      occur when there are no apparent pre-disposing mechanical or inflammatory causes
      although a few of these patients may harbour an occult malignant neoplasm. Hence,
      careful investigation and follow-up are vital. Thrombosis in Trousseau's syndrome
      is usually confined to the vascular system of the extremities and the viscera.
      However, secondary to the paraneoplastic hypercoagulable state, thrombosis can
      occur in the large veins of the head and neck region. We understand this to be
      the first case where spontaneous internal jugular vein thrombosis and ipsilateral
      recurrent laryngeal nerve paralysis were the only initial manifestations of an
      occult malignancy.

PMID- 9015436
TI  - Intraparotid facial nerve schwannoma in a child.
AB  - Neoplasms of the facial nerve presenting as a parotid mass are uncommon. In the
      absence of a facial palsy their origin from the nerve is usually diagnosed
      intraoperatively. The majority of these neurogenic neoplasms are schwannomas,
      with neurofibromas occurring rarely. Although the Schwann cell is the key element
      in both, they have distinct histopathological characteristics, and their clinical
      course and management often differs. The first reported case of an intraparotid
      facial nerve schwannoma in a child in the English literature is presented.

PMID- 9015437
TI  - Atypically located submandibular gland diagnosed by Doppler ultrasound.
AB  - The anatomical location and relationships of the submandibular gland are well
      known to most otolaryngologists and gross variations from the norm are rare. We
      report a case of an atypical submandibular gland located 2 cm below the mandible
      which presented as a painful neck swelling with non-diagnostic fine needle
      aspiration cytology. Using Doppler ultrasound the mass was noted to be closely
      located to the facial artery and vein and following the administration of oral
      lemon juice, the peak systolic velocity of a small artery within the mass rose
      from 8.5 cm/s to 16.4 cm/s, confirming the tissue's salivary nature. We review
      the literature on using Doppler ultrasound in this area of the neck and discuss
      realistic practical applications of the technique.

PMID- 9015438
TI  - Solitary plexiform neurofibroma of the submandibular salivary gland.
AB  - Neurofibroma affecting the major salivary gland is uncommon. This tumour is
      particularly rare in the submandibular and sublingual gland. Here, a case of
      solitary plexiform neurofibroma of the submandibular gland without any other
      manifestations of von Recklinghausen's disease is presented. It is probably the
      first case report of this tumour invading the submandibular gland in a solitary
      form.

PMID- 9015439
TI  - Thyroid carcinoma causing fatal laryngeal occlusion.
AB  - Pure squamous carcinoma of the thyroid gland is an uncommon tumour and is thought
      to arise in glands containing metaplastic squamous epithelium. Extrinsic
      compression or tumour invasion of the larynx causing fatal respiratory
      obstruction are recognized complications. We report a case of primary squamous
      carcinoma of the thyroid gland where obstruction of laryngeal mucous gland
      outflow resulted in fatal laryngeal compression. This appears to be the first
      description of such a sequence of events.

PMID- 9015440
TI  - Primitive neuroectodermal tumour of the masseter muscle.
AB  - Masseter muscle enlargement is one of the differential diagnoses of swelling of
      the cheek. We discuss a unique case of a malignant tumour of the masseter which
      was found to be a peripheral primitive neuroectodermal tumour (PNET). A review of
      tumours of the masseter is presented.

PMID- 9015441
TI  - Is a community-based mastoid microsuction service feasible: the audit of a pilot
      project.

PMID- 9015442
TI  - Analysis of CT scanning referrals for chronic rhinosinusitis.

PMID- 9015443
TI  - The Birmingham bone anchored hearing aid programme: surgical methods and
      complications.
AB  - Since 1988, 309 patients have been referred to the Birmingham bone anchored
      hearing aid programme for assessment. One hundred and eighty-eight have been
      fitted with bone anchored hearing aids (BAHA). Of these 169 have been fitted with
      a BAHA alone and 20 with a BAHA and auricular prosthesis(es). Only four (2.1 per
      cent) are not wearing their BAHAs. Three cases because the hearing had continued
      to deteriorate and in one case because of repeated failure to integrate. Nineteen
      patients (10.1 per cent) have lost fixtures but all but one of these have been
      successfully reimplanted. Of these 19 patients 10 (52.6 per cent) were syndromal
      and 10 (52.6 per cent) were under 16 years of age. A surgical method has been
      evolved both to cope with predictable failure of integration and soft tissue
      control.

PMID- 9015444
TI  - The Birmingham bone anchored hearing aid programme: referrals, selection,
      rehabilitation, philosophy and adult results.
AB  - The Birmingham bone anchored hearing aid team is part of the Birmingham
      osseointegrated programme. In the first seven years of its existence it has
      received 309 referrals. Twenty-six per cent had suffered a congenital conductive
      hearing loss and 74 per cent had an acquired conductive hearing loss; the
      majority secondary to chronic suppurative otitis media. This report is of 68 out
      of 106 adults wearing bone anchored hearing aids (BAHAs). Ninety-eight per cent
      showed audiological improvement with the congenital group demonstrating
      marginally the best free-field thresholds and speech discrimination.
      Questionnaire data as to the patient experience confirms the benefits especially
      hearing in noise, and comfort, and the vast majority were more satisfied with the
      bone anchored hearing aid than their previous aid.

PMID- 9015445
TI  - The Birmingham bone anchored hearing aid programme: paediatric experience and
      results.
AB  - Over a five-year period, 34 patients have been referred to the Birmingham bone
      anchored hearing aid programme, paediatric section, of who 21 are now wearing the
      bone anchored hearing aid (BAHA) and four are awaiting surgery for fitting of the
      BAHA. Of the patients assessed, found to be suitable and who proceeded to surgery
      for the BAHA, 44 per cent had Treacher Collins syndrome, 28 per cent had
      bilateral atresia or microtia, 16 per cent had Goldenhaar's syndrome, four per
      cent (one patient) had branchio-otorenal syndrome and eight per cent had chronic
      suppurative otitis media. This paper presents objective and subjective data
      collected from these patients. It is shown that the BAHA is a very effective
      hearing aid for children with congenital hearing loss.

PMID- 9015446
TI  - The bone anchored hearing aid--the third option for otosclerosis.
AB  - The bone anchored hearing aid (BAHA) has mainly been used for the treatment of
      hearing loss in patients with congenital conductive problems or chronic
      suppurative otitis media. In a five-year period, 32 otosclerotic patients have
      been referred to the Queen Elizabeth Hospital for consideration of a BAHA. Ten of
      these patients have been fitted and gained benefit compared to their previous
      hearing aid. The benefits are not necessarily those in hearing ability but in
      some cases relate to cosmetic or comfort improvements. This paper demonstrates
      that the BAHA offers a third treatment option for otosclerosis in patients who
      cannot or will not undergo stapedectomy and experience difficulty with
      conventional hearing aids.

PMID- 9015447
TI  - The bone anchored hearing aid (BAHA) in chronic suppurative otitis media (CSOM).
AB  - Bone anchored hearing aids are gaining wide acceptability in the treatment of
      patients with congenital ear problems, chronic suppurative otitis media (CSOM)
      and in some cases otosclerosis. To date little information on the effect of the
      bone anchored hearing aid on the symptoms of chronic suppurative otitis is
      available. This retrospective study based on notes review and telephone
      interviews was to assess the outcome of bone anchored hearing aid surgery in
      patients with CSOM in terms of: ear discharge; surgical techniques and
      complications; the number of hours the aid is worn compared with the previous
      aid. One hundred and forty-two patients were fitted with bone anchored hearing
      aids without additional prostheses in Birmingham between 1989 and 1995. Sixty
      nine (48.5 per cent) of these were for chronic suppurative otitis media, 45 of
      these were female and 24 were male with a mean age of 58 years. Most (85 per
      cent) had undergone previous ear surgery with 65 per cent having mastoid surgery.
      Ninety-eight per cent of this patient group had undergone single stage surgery
      and 65 per cent under local anaesthetic as a day case. A variety of techniques
      for soft tissue reduction were employed. The mean follow-up time for these
      patients was 24 months (range one month to seven years). No patients experienced
      worse discharge following their BAHA and 84 per cent had significantly reduced
      discharge, 16 per cent had no change. Complications included skin reactions, 15;
      failure to integrate, one; late loss of fixture, three. Seventy-three per cent
      wore their bone anchored hearing aid more than eight hours per day and 58 per
      cent were more satisfied with their bone anchored hearing aid than their previous
      aid.

PMID- 9015448
TI  - Bone anchored hearing aid wearers with significant sensorineural hearing losses
      (borderline candidates): patients' results and opinions.
AB  - Bone anchored hearing aids (BAHA) have been implanted in Birmingham since 1988.
      Since this time confidence has grown in the fitting and rehabilitation of BAHA
      wearers, with corresponding increase in the implantation and rehabilitation of
      more difficult and borderline candidates. This study analyses the results of 16
      borderline BAHA candidates who have been assessed and fitted with a BAHA at
      Birmingham Children's Hospital and Queen Elizabeth Hospital, and who have had at
      least one post-fitting review. All of these subjects had mean bone conduction
      (BC) thresholds, in the better hearing ear, in excess of 45 dBHL in the frequency
      range 0.5-4 kHz, when initially assessed. The age range at the time of the study
      was 10-84 years, with a mean age of 60 years. The study demonstrates the benefits
      that these patients achieved with the BAHA compared to their previous aid, both
      audiologically and in terms of comfort and reduction in ear discharge.

PMID- 9015449
TI  - Speech and voice rehabilitation in selected patients fitted with a bone anchored
      hearing aid (BAHA).
AB  - With the Birmingham osseointegrated implant programme there have been several
      patients with severe pre-lingual conductive hearing loss. The majority of these
      have been patients with Treacher Collins syndrome. There are characteristic
      features of speech and voice in those with long-standing conductive hearing loss.
      In addition, the associated abnormalities of jaw, teeth and palate may amplify
      the problem. There may be spontaneous improvement in features such as voice
      pitch, quality and intensity following the fitting of a BAHA. However, in those
      with a pre-lingual hearing impairment, speech therapy may be necessary. Patients
      assessed as suitable for BAHA have a full assessment of communication skills
      including audio recording of speech and voice. Post-operative training improves
      auditory discrimination and perception and is followed by training in the
      production of the newly perceived speech sounds.

PMID- 9015450
TI  - Counting and classifying attractors in high dimensional dynamical systems.
AB  - Randomly connected Boolean networks have been used as mathematical models of
      neural, genetic, and immune systems. A key quantity of such networks is the
      number of basins of attraction in the state space. The number of basins of
      attraction changes as a function of the size of the network, its connectivity and
      its transition rules. In discrete networks, a simple count of the number of
      attractors does not reveal the combinatorial structure of the attractors. These
      points are illustrated in a reexamination of dynamics in a class of random
      Boolean networks considered previously by Kauffman. We also consider comparisons
      between dynamics in discrete networks and continuous analogues. A continuous
      analogue of a discrete network may have a different number of attractors for many
      different reasons. Some attractors in discrete networks may be associated with
      unstable dynamics, and several different attractors in a discrete network may be
      associated with a single attractor in the continuous case. Special problems in
      determining attractors in continuous systems arise when there is aperiodic
      dynamics associated with quasiperiodicity of deterministic chaos.

PMID- 9015451
TI  - Toxicity and neuroendocrine regulation of the immune response: a model analysis.
AB  - Various models have been proposed for the regulation of the primary immune
      response. Most of the models focus on the ability of the immune system to control
      a multiplying pathogen, and take into account the cross-regulations between
      different immune components. In the present study, we integrate the immune system
      in the general physiology of the host and consider the interaction between the
      immune and neuroendocrine systems. In addition to pathogen growth and toxicity,
      our four-variable model takes into account the toxic consequences for the
      organism of the immune response itself, as well as a neuro-hormonal retro-control
      of this immune response. Formally, the dynamics of the model is first explored on
      the basis of a discrete caricature, with special emphasis on the role of the
      constitutive feedback loops for determining the essential dynamical behavior of
      the system. This logical analysis is then completed by a classical continuous
      approach using differential equations. From a biological point of view, our model
      accounts for four stable regimes which can be described as "pathogen
      elimination/organism healthy", "pathogen elimination/ organism death", "pathogen
      growth/organism death" and "chronic infection". The size of the basins of
      attraction of these different regimes varies as a function of some crucial
      parameters. Our model allows moreover to interpret the interplay between pathogen
      immunogenicity and neuro-hormonal feedback, the effects of stress on immunity and
      the toxic shock syndrome, in terms of transitions among the steady states.

PMID- 9015452
TI  - A possible role of adenylate metabolism in human erythrocytes. 2. Adenylate
      metabolism is able to improve the erythrocyte volume stabilization.
AB  - We constructed and studied a mathematical model that describes the control of
      cell volume, ion balance, energy and adenylate metabolism in human erythrocytes.
      According to the model, adenylate metabolism can provide an effective
      stabilization of the cell volume over relatively large changes of cell
      parameters. For example, the steady-state value of cell volume remains almost
      unchanged when the cell membrane permeability increases by 15-fold. The cell
      volume also changes only slightly over large changes in the parameters of energy
      metabolism. The relaxation time for the cell volume changes is about 100 hr over
      changes in these parameters. In other words, the volume stabilization operates
      most effectively against long-term slow perturbations.

PMID- 9015453
TI  - Triplet correlation in DNA sequences and stability of heteroduplexes.

PMID- 9015454
TI  - Four stereochemical types of protein amino acids: synchronic determination with
      chemical characteristics, atom and nucleon number.

PMID- 9015455
TI  - Control of apolipoprotein B mRNA editing: implication of mRNA dynamics at various
      maturation stages.
AB  - Apolipoprotein (apo) B mRNA editing is a genetic regulatory mechanism whereby
      nucleotide 6666 in apo-B-100 mRNA is converted from a C to a U. The end result of
      this change is the creation of a premature stop codon so that the translation
      product of the edited (apoB-48) mRNA contains 2152 amino acids residues instead
      of 4536 residues in the product (apoB-100) encoded by the unedited mRNA. ApoB
      mRNA editing is a post-transcriptional process that is expressed in a tissue
      specific manner. Here we present a model for the control of apoB mRNA editing.
      The three variables in the model include editing activity, apoB mRNA
      transcription rate and mRNA degradation rate at various maturation stages for the
      mRNA, and a simple formula can be used to quantify the degree of apoB mRNA
      editing with respect to these variables at different apoB mRNA maturation stages.
      Time-dependent equations were solved numerically. Using this model, it can be
      shown that, in addition to editing activity, the degradation kinetics of apoB
      mRNA can also serve as an efficient modulator of the degree of editing. The rate
      of apoB mRNA transcription has a transient effect on the degree of editing;
      varying the apoB mRNA degradation constant tends to change the degree of editing
      only at the specific maturation stage. This model can render some previously
      proposed hypothesis (e.g. coupling of mRNA editing to splicing/polyadenylation)
      unnecessary and provides a rational basis for the design of experiments on
      specific aspects of apoB mRNA editing in the future; it may also be applicable to
      other types of RNA editing.

PMID- 9015456
TI  - Size and connectivity of the idiotypic network are independent of the
      discreteness of the affinity distribution.
AB  - Idiotypic interactions may be a factor in the selection of the B cell repertoire.
      Simulations of an evolving idiotypic network where new clones are introduced on a
      daily basis have shown that macroscopic properties, such as network size and
      connectivity, attain stationary values despite the rapid turnover of individual
      clones, indicating that idiotypic networks possess self-organizing properties.
      Affinities between antibodies were either zero, low (0.1), or high (1.0) in these
      simulations. It has been suggested that network properties may change when
      affinities take arbitrary real values. Here we show that the previous results of
      De Boer & Perelson on network size and connectivity are not changed when
      affinities take many different, closely spaced values.

PMID- 9015457
TI  - On the dangers of adjusting the parameters values of mechanism-based mathematical
      models.
AB  - Mechanism-based mathematical models describe systems in terms of identifiable
      physical processes, and the parameters are assumed to have fundamental physical
      significance. Ideally, the parameter values are measured independent of the
      system being modeled, but these values are often adjusted to give the best fit of
      model predictions to experimental data. A systematic investigation of the effects
      of such parameter adjustment was conducted by developing a model system
      comprising a known reaction mechanism and known rate constants. Simulations of
      experiments were run, and then attempts were made to model the system under a
      variety of problematic, but realistic, conditions. (1) When one rate constant was
      seriously in error, adjustment of a different rate constant gave the greatest
      improvement in the model fit. (2) When a contaminant was present in the
      experiment, the effects could be hidden by the adjustment of the rate constants.
      (3) When an incorrect reaction mechanism was assumed, the error could be hidden
      by parameter adjustment if the concentrations of only one of the reacting species
      were considered or if an unweighted fit was used for the optimization. (4)
      Parameter values adjusted for one set of experimental conditions gave a poorer
      fit than did the unadjusted parameter values when attempting to model a new set
      of experimental condition (addition of an inhibitor). These results show the
      potential dangers of adjusting parameter values and the importance of measuring
      as many variables as possible in a complex system.

PMID- 9015458
TI  - Pattern formation by lateral inhibition with feedback: a mathematical model of
      delta-notch intercellular signalling.
AB  - In many developing tissues, adjacent cells diverge in character so as to create a
      fine-grained pattern of cells in contrasting states of differentiation. It has
      been proposed that such patterns can be generated through lateral inhibition--a
      type of cell-cell interaction whereby a cell that adopts a particular fate
      inhibits its immediate neighbors from doing likewise. Lateral inhibition is well
      documented in flies, worms and vertebrates. In all of these organisms, the
      transmembrane proteins Notch and Delta (or their homologues) have been identified
      as mediators of the interaction--Notch as receptor, Delta as its ligand on
      adjacent cells. However, it is not clear under precisely what conditions the
      Delta-Notch mechanism of lateral inhibition can generate the observed types of
      pattern, or indeed whether this mechanism is capable of generating such patterns
      by itself. Here we construct and analyse a simple and general mathematical model
      of such contact-mediated lateral inhibition. In accordance with experimental
      data, the model postulates that receipt of inhibition (i.e. activation of Notch)
      diminished the ability to deliver inhibition (i.e. to produce active Delta). This
      gives rise to a feedback loop that can amplify differences between adjacent
      cells. We investigate the pattern-forming potential and temporal behaviour of
      this model both analytically and through numerical simulation. Inhomogeneities
      are self-amplifying and develop without need of any other machinery, provided the
      feedback is sufficiently strong. For a wide range of initial and boundary
      conditions, the model generates fine-grained patterns similar to those observed
      in living systems.

PMID- 9015459
TI  - Oscillatory dynamics of smallpox and the impact of vaccination.
AB  - The evolution of smallpox epidemics in London, 1647-1893, was studied by time
      series analysis of deaths from the disease in the Bills of Mortality. The
      interepidemic interval (T) evolved progressively from 4 years to 2 years at 1800.
      The dynamics of epidemics during 1647-1800 are explicable in terms of the
      transmission of viral diseases which shows that (i) T is determined by the
      product of population size (N) and susceptibility (beta), (ii) T determines the
      mean age of catching the disease, (iii) the system will settle at its steady
      state, endemic level unless the epidemics are driven. It is suggested that (i)
      the progressive change in T was initially caused by a rise in N and later by an
      increased beta related to malnutrition and (ii) the epidemics were driven by an
      oscillation in delta beta associated with seasonal dry conditions. The effects of
      variolation and vaccination became apparent after 1800: the endemic level fell
      progressively, the epidemics were reduced in amplitude and they were not driven.
      The dynamics of the disease can now be described by an SEIR model: severe
      outbreaks of smallpox are followed by decaying epidemics. Endemic smallpox
      mortality also interacts with the dynamics of the population so that a long
      wavelength oscillation (associated with recovery after the plague) and a 5/6 year
      (associated with immigration) oscillation are generated.

PMID- 9015460
TI  - Analysis of genomic patchiness of Haemophilus influenzae and Saccharomyces
      cerevisiae chromosomes.
AB  - We have analysed some aspects of the primary structure of the chromosome of the
      prokaryote Haemophilus influenzae and of the eukaryote Saccharomyces cerevisiae
      that share the same G + C content. In particular, we have investigated genomic
      patchiness over the gene size level (10 Kb) and that patchiness due to long
      homogenous tracts. Long polypurine and polypyrmidine tracts that are largely over
      represented in S. cerevisiae chromosomes and under-represented in H. influenzae,
      are responsible for a large fraction of long correlation signals. Generating
      mechanisms of long homogenous tracts are DNA replication slippage and duplication
      events that appear to be linked processes driving chromosome primary structure
      evolution.

PMID- 9015461
TI  - Improving the early diagnosis of acute myocardial infarction.
AB  - The diagnosis of early myocardial infarction, especially in association with
      atypical clinical presentations, can be difficult to establish. Continued
      observation of high-risk patients, with multiple serial electrocardiographs and
      the use of other diagnostic modalities as available, is essential to prevent the
      inadvertent premature discharge of patients with evolving myocardial infarcts
      from the accident and emergency department.

PMID- 9015462
TI  - Interferon-alpha in childhood haematological malignancies.
AB  - The application of cytostatics has brought about a breakthrough in the treatment
      of childhood haematological malignancies in the past 20 years. Chemotherapy
      appears to be least successful in the rare, low and very high mitotic index
      diseases, which often have an enormous tumour-burden. The suitability of
      chemotherapy in minimal residual leukaemia is also of some doubt. In these
      situations a 'conservative' treatment may be more appropriate. Because interferon
      alpha has a distinct mechanism of action, and a broad-spectrum haematopoietic
      inhibitory activity, it is relatively nontoxic and noncancerogenic, and it may
      have a role in the treatment of malignant haematological disorders, either as a
      mono- or combination therapy. The exact indications and dosages for interferon in
      childhood malignancies are far from clear. Up to now, it has proved to be most
      efficacious in small tumour masses, providing a theoretical basis for application
      in minimal residual disease. Controlled clinical data, however, are not yet
      available. It remains to be determined whether or not interferon can be added to
      current chemotherapy protocols without a significant reduction of dose.
      Hopefully, a deeper understanding of the activities of interferon will allow us
      to plan better trials with combination treatments.

PMID- 9015463
TI  - The role of cigarettes and nicotine in the onset and treatment of ulcerative
      colitis.
AB  - Epidemiological evidence suggests that ulcerative colitis is a disease of
      nonsmokers, while Crohn's disease is a disease of smokers. The relative risk of
      developing ulcerative colitis is not only greater in nonsmokers, in addition
      there appears to be a rebound effect in smokers who quit, with the heaviest (ex
      )smokers increasing their relative risk of the disease the most. This factor
      poses an ethical dilemma for health professionals giving advice on stopping
      smoking, which may thus have a serious detrimental effect on the health of some
      patients. Nicotine is believed to be the pharmacological ingredient of tobacco
      that is responsible for this beneficial effect and several clinical trials using
      nicotine have demonstrated it to be an effective therapeutic agent in the
      treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is
      unclear, current research using nicotine-based products has produced some
      interesting clues, together with the possibility of some form of therapeutic
      treatment based on nicotine administration.

PMID- 9015464
TI  - Bladder cancer.
AB  - Bladder cancer is the fourth most common cancer in England and Wales. The most
      common presenting symptom is macroscopic haematuria. The management options for
      superficial and invasive bladder cancer depend on the stage at presentation. Most
      superficial bladder cancers are managed by transurethral resection and cytoscopic
      follow-up. The prognosis for patients with invasive bladder cancer is less good.
      The role of chemical, radiotherapeutic and surgical intervention are discussed.

PMID- 9015465
TI  - Ophthalmic complications of HIV/AIDS.
AB  - As a result of improved treatment and patient survival, ophthalmic complications
      are now being seen with increasing frequency in AIDS, occurring in up to 75% of
      patients during the course of the disease. The eye may be involved by an AIDS
      related microvasculopathy, which gives rise to cotton wool spots, and by
      opportunistic infections caused by a wide range of organisms, including
      cytomegalovirus, herpes simplex virus, varicella zoster, Toxoplasma gondii,
      Mycobacterium avium-intracellulare, Treponema pallidum, Pneumocystis carinii and
      various fungal agents. Opportunistic infections may be the presenting sign of
      disseminated infection. The eye may also be involved by neoplasms such as
      Kaposi's sarcoma and lymphoma, and by intracranial disease. Ocular involvement
      may lead to blindness if untreated and prompt ophthalmological referral is
      essential. This article reviews the range of ocular diseases seen in HIV and
      AIDS, current therapeutic options and outcome.

PMID- 9015466
TI  - Intracardiac thrombus formation in cardiac impairment: the role of anticoagulant
      therapy.
AB  - The presence of intracardiac thrombus has been associated with many diseases and
      clinical states, although cardiac impairment is commonly also present. Despite
      this, there continues to be a lack of consensus on which patients with cardiac
      impairment should have anticoagulant therapy. This review discusses the
      relationship between thromboembolism and cardiac impairment secondary to
      ischaemic heart disease, and suggests possible mechanisms, methods of diagnosis
      and therapeutic strategies for anticoagulation in such patients. In particular,
      warfarin has been established as thromboprophylaxis in certain subgroups of
      patients with cardiac impairment secondary to ischaemic heart disease. A large
      scale randomised controlled trial in ambulant patients with cardiac impairment to
      evaluate the effectiveness of anticoagulant therapy and antiplatelet therapy is,
      however, long overdue.

PMID- 9015467
TI  - Comparative efficacy and safety of ciprofibrate and sustained-release bezafibrate
      in patients with type II hyperlipidaemia.
AB  - The hypolipidaemic efficacy and safety of ciprofibrate were compared with a
      sustained-release formulation of bezafibrate (Bezalip Mono) in 174 patients with
      type II hyperlipidaemia. This multicenter, open, parallel-group study was
      conducted in general practice. A total of 83 patients received 100 mg
      ciprofibrate once daily and 91 received 400 mg bezafibrate once daily for eight
      weeks. Concentrations of total cholesterol, low-density lipoprotein cholesterol,
      high-density lipoprotein cholesterol, and triglycerides were measured at baseline
      (after stabilisation on a lipid-lowering diet) and after eight weeks. Safety was
      assessed from reports of adverse events and by measuring haematological and
      biochemical parameters. After eight weeks, ciprofibrate produced a significantly
      greater decrease in total cholesterol (-17.8% vs -12.5%), low-density lipoprotein
      cholesterol (-22.4% vs -17.2%), and triglycerides (-33.9% vs -26.1%). High
      density lipoprotein cholesterol concentrations were increased significantly by
      both drugs (19.6% with ciprofibrate, 24.9% with bezafibrate) but the differences
      between drugs were non-significant. Both drugs were well tolerated, with headache
      the most widely reported adverse event.

PMID- 9015468
TI  - The one-stop coronary cholesterol clinic: a multidisciplinary approach to
      implementing evidence-based treatment.
AB  - We describe a 'one-stop' cholesterol clinic implementing a regime based on the
      Scandinavian Simvastatin Survival Study (4S) in patients with established
      coronary heart disease in a district general hospital. The clinic has been
      established in collaboration with the cardiac rehabilitation centre. It was
      commissioned as an audit project by the purchasing authority, Walsall Health, a
      need having been shown in a previous audit. In the new clinic, audit is inbuilt,
      rather than being carried out as a separate retrospective exercise, and
      undertaken prospectively for all patients. Central to this is a database, used
      for routine correspondence and administration, as well as monitoring outcome.
      This application of information technology has improved clinical practice.
      Attendance at the clinic has been excellent. Half the consultations have resulted
      in therapeutic interventions, many of which may otherwise have been missed. Over
      50% of patients were eligible for lipid-lowering medication under the protocol.
      Cholesterol targets based on 4S were achieved but with much lower drug doses,
      which may have major cost implications. Cholesterol levels measured within 24
      hours of admission for myocardial infarction were poor predictors of results
      obtained after convalescence. After the clinic visit, most patients were taking
      aspirin plus one or two other secondary prevention treatments. Guidelines have
      been issued to primary care. Future plans for audit links with general
      practitioners, integration of the metabolic and cardiological assessment of
      survivors of myocardial infarction, and for long-term monitoring of clinical
      events in treated patients are discussed.

PMID- 9015469
TI  - Successful treatment of intracaval and atrial extension of Wilms' tumour by
      chemotherapy.
AB  - A patient presenting with advanced Wilm's tumour was diagnosed as having inferior
      vena cava involvement with tumour thrombus extending up to the right atrium, and
      was treated with preoperative chemotherapy (vincristine, actinocymin D,
      epirubicin). Atrial and inferior vena cava thrombus disappeared and he underwent
      a successful nephrectomy.

PMID- 9015470
TI  - Nonvalvular myocardial involvement in metastatic carcinoid disease.
AB  - A patient with the unusual post mortem finding of myocardial metastatic carcinoid
      tumour without classical valvular or endocardial carcinoid disease is described.
      This rare occurrence may represent an aggressive type of carcinoid tumour, with
      metastatic disease occurring before the development of classical fibrous valvular
      and endocardial pathology.

PMID- 9015471
TI  - A patient with hepatitis B, antimicrosomal antibodies, and autoimmune
      hypothyroidism.
AB  - A 37-year-man with chronic hepatitis B was diagnosed as having antimicrosomal
      antibodies and subclinical hypothyroidism. The association of autoimmune
      manifestations with hepatitis B has been less frequently reported than with
      hepatitis C virus. It is discussed whether this patient illustrates a case of
      spontaneous development of antimicrosomal antibodies, only casually associated
      with the presence of hepatitis B virus, or there is a real causative relationship
      between both conditions.

PMID- 9015472
TI  - Spontaneous healing of osteitis fibrosa cystica in primary hyperparathyroidism.
AB  - A 24-year-old man with primary hyperparathyroidism and osteitis fibrosa cystica
      developed acute hypocalcaemia. Spontaneous healing of his bone disease was
      confirmed radiographically and by correction of the serum alkaline phosphatase.
      Hypercalcaemia associated with a raised serum parathyroid hormone recurred 90
      weeks after the initial presentation. During the fourth neck exploration a
      parathyroid adenoma was removed, resulting in resolution of his condition.
      Haemorrhagic infarction of an adenoma was the most likely cause of the acute
      hypocalcaemic episode.

PMID- 9015473
TI  - Cefuroxime-induced thrombocytopenia?

PMID- 9015474
TI  - Ureteric filling defect.

PMID- 9015475
TI  - Skin lesions as the presenting symptom of a gastrointestinal disease.

PMID- 9015477
TI  - Thrombotic thrombocytopenic purpura in pregnancy.

PMID- 9015476
TI  - Acute renal failure with chronic lymphocytic leukaemia.

PMID- 9015478
TI  - Legal aspects of venepuncture.

PMID- 9015479
TI  - Splenic infarction related to cocaine use.

PMID- 9015480
TI  - Self-poisoning and the general hospital.

PMID- 9015481
TI  - Adrenomedullin: a novel cardiovascular regulatory peptide.

PMID- 9015482
TI  - The prospects for xenotransplantation.

PMID- 9015483
TI  - Changing patterns of self-poisoning in a UK health district.
AB  - Details of admissions to a dedicated district poisons treatment unit in South
      Glamorgan were analysed to assess changes in self-poisoning patterns between 1987
      1988 and 1992-1993. Self-poisoning rates increased in both men and women, with
      male rates showing a relatively larger increase, resulting in a fall in female to
      male ratio for person-based rates from 1.33:1 to 1.13:1. The highest age-specific
      rates in both period were found in 15-19-year-old females. Paracetamol was the
      most commonly ingested poison in 1992-1993, with 43.4% of episodes involving its
      use, compared with 31.3% of episodes in 1987-88. Antidepressant involvement in
      self-poisoning also increased from 11.3% of episodes in 1987-1988 to 17.6% of
      episodes in 1992-1993. Repetition of self-poisoning was relatively common, with
      18% of admissions per year in 1992-1993 representing repeats. Although hospital
      admission increased in this health district over the study periods, this was not
      reflected in an increase in in-patient all-cause mortality, which was only 0.5%
      in 1987-1988 and 0.1% in 1992-1993.

PMID- 9015484
TI  - Treatment of refractory Wegener's granulomatosis with humanized monoclonal
      antibodies.
AB  - Conventional immunosuppression for systemic vasculitides is limited by
      substantial side-effects, cumulative drug toxicity and refractoriness in some
      patients. Six Wegener's granulomatosis patients who had been refractory to
      conventional therapy for at least 6 months, were treated with humanized
      monoclonal antibodies specific to lymphocyte CD52 or CD4 antigens. Diagnosis was
      on clinicopathological grounds, supported by the presence of autoantibodies to
      Proteinase 3. Histological evidence of persistent disease activity was obtained
      for each patient. Humanized monoclonal anti-CD52, with or without anti-CD4, was
      given intravenously up to 40 mg/day for up to 10 days. Remission, (programmed
      withdrawal of drug therapy without return of refractory disease) was achieved in
      all patients. Cytotoxic drugs were discontinued at the time of monoclonal
      antibody treatment and not used again; steroids were withdrawn gradually. Four
      patients relapsed at 1.5, 5, 10 and 18 months, and were treated successfully with
      further monoclonal antibody therapy alone. Three years after the study began,
      five patients are well; one patient died at surgery whilst in remission.
      Humanized monoclonal antilymphocyte antibodies may provide an effective treatment
      in patients with systemic vasculitis which is refractory to steroids or cytotoxic
      agents, or who are intolerant of these drugs.

PMID- 9015485
TI  - Diagnosis and treatment of status epilepticus on a neurological intensive care
      unit.
AB  - Status epilepticus refractory to first-line therapy is associated with a high
      morbidity and mortality. Correct diagnosis and adequate treatment of this
      condition require electrographic monitoring and anaesthetic facilities available
      in specialist intensive care units (ICUs). We carried out an audit of 26 patients
      admitted to a neurological ICU with a diagnosis of status epilepticus, to
      identify deficiencies in diagnosis and management prior to transfer to the ICU,
      and examine the effectiveness of ICU management. Or transfer, only 14 (54%) were
      in status epilepticus; six were in drug-induced coma or were encephalopathic, and
      six had pseudostatus epilepticus, of whom four had been intubated. The commonest
      treatments prior to transfer were benzodiazepines, chlormethiazole and phenytoin;
      the loading dose of phenytoin was adequate in at least 7/16 cases. All those in
      status epilepticus on transfer had their seizures successfully controlled, but
      ten required general anaesthesia with thiopentone, propofol, ketamine or
      midazolam. Two died--one had a severe encephalitis and the other had had a
      cardiac arrest prior to treatment. This study highlights deficiencies in the
      initial diagnosis and management of status epilepticus, the role of specialist
      neurological intensive care, and the importance of early referral.

PMID- 9015486
TI  - Primary hyperparathyroidism in a paediatric hospital.
AB  - We retrospectively reviewed the presentation and management of children with
      primary hyperparathyroidism (PHPT) from 1973 to 1995 at a paediatric tertiary
      care centre. There were 11 patients (6 females), aged 12.3-17.7 years at
      presentation, with sporadic PHPT confirmed by histopathology (single adenoma).
      Presentation consisted of renal colic, or non-specific gastrointestinal,
      musculoskeletal or neurological symptoms. Misdiagnosis was common until
      hypercalcaemia was identified, 0.5-24 months after onset of symptoms (mean 7.7
      months). All patients had hypercalcaemia and low-normal serum phosphate. The
      parathyroid hormone (PTH) radioimmunoassay used before 1986 was elevated in 1/4
      patients; the intact PTH assay used after 1986 was elevated in 7/7 patients. At
      presentation, six had end-organ damage: band keratopathy, renal lesions, and/or
      bone disease. Preoperative localization was accurate in 0/4 patients diagnosed
      before 1986, but 5/7 patients diagnosed after 1986: three by ultrasound or
      sestamibi scan alone, and two by ultrasound and technetium scan. Surgical outcome
      was not dependent upon the accuracy of pre-operative localization. PHPT is rare
      in children but usually associated with end-organ damage, presumably due to
      delayed diagnosis. It should be considered in the differential diagnosis of
      unexplained non-specific complaints. The intact PTH assay greatly assists pre
      operative diagnosis. The usefulness of pre-operative localization requires
      further research.

PMID- 9015487
TI  - Klebsiella bacteraemia: community versus nosocomial infection.
AB  - In the period 1988-1993, 241 patients had Klebsiella bacteraemia at our medical
      centre. The annual number of patients with positive blood cultures increased from
      306 in 1988 to 622 in 1993, representing a 4.5-6% positivity rate of drawn
      cultures. After E. coli, Klebsiella was the leading cause of Gram-negative
      bacteraemia. During this period, the absolute number of Klebsiella bacteraemia
      increased from 25 in 1988 to 84 in 1993; this represents a true increase in
      Klebsiellaa bacteraemia, from 6-7% of positive cultures in the late 1980s to 12
      13% in more recent years. There were 210 cases with K. pneumoniae and 31 with K.
      oxytoca. A representative sample of 80 records was retrieved and subdivided into
      two groups: community-acquired Klebsiella bacteraemia (CAKB) vs. hospital
      acquired Klebsiella bacteraemia (HAKB). Urinary tract infection was the
      underlying source of 58% of CAKB vs 28% of HAKB (p < 0.01); pneumonia occurred
      significantly more often in HAKB (25%) than in CAKB (7%) (p < 0.01). In HAKB, as
      compared to CAKB, serious manifestations of illness were more common, e.g. shock
      (65% vs. 37%, p < 0.046) and respiratory failure (45% vs. 20%, p < 0.046).
      Overall mortality was 32%, 22% of patients with CAKB died vs. 42% of those with
      HAKB (p < 0.05). Multiple drug resistance was very common: only 57% of all
      Klebsiella strains were susceptible to gentamicin, 66% to ceftriaxone, 70% to
      ciprofloxacin, and 83% to amikacin. The susceptibility rates of Klebsiella spp
      isolated from patients with HAKB were significantly lower (p < 0.001). Sepsis due
      to multiple-drug-resistant Klebsiellaa has become frequent, carrying significant
      morbidity and mortality. Restriction of broad-spectrum antimicrobials in the
      hospital and the community as well as implementation of infection control
      measures are needed to contain this problem.

PMID- 9015488
TI  - How does hyperglycaemia predispose to diabetic nephropathy?
AB  - Diabetic nephropathy is preceded by 'hyperfiltration' mediated by dilatation of
      the afferent arterioles to the glomeruli by means of IGF-1, prostaglandins,
      bradykinin, nitric oxide and atrial natriuretic peptide, together with
      constriction of the efferent arterioles by local thromboxane A2. Raised
      glomerular intracapillary pressures might then contribute to glomerulosclerosis,
      but in any case there is permeability of the vascular endothelium. AGEPs and
      lipid peroxides can explain this. AGEPs, or simply intermittently high levels of
      glucose, also account for synthesis of extracellular matrix proteins that lead to
      thickening of the basement membrane and glomerulosclerosis. Another glucose
      product, glucosamine-6-phosphate, is formed when there is hexosamine flux along
      with insulin resistance in tissues, and is implicated in glomerulosclerosis,
      since it also stimulates TGF-beta transcription. In seeking to explain
      proteinuria, depletion of heparan sulphates from the endothelial cells and GBM is
      now established as a principal cause. In addition to a high glucose reducing the
      synthesis of heparan sulphates, it has now been shown that high glucose may
      depress the synthesis of heparin sulphate proteoglycan.

PMID- 9015489
TI  - Iatrogenic chest pain: a case of 5-fluorouracil cardiotoxicity.

PMID- 9015490
TI  - Injuries in developing countries: policy response needed now.

PMID- 9015491
TI  - Novel anthelmintic compounds and molluscicides from medicinal plants.
AB  - This review assesses the role that can be played by allelochemicals (bioactive
      secondary compounds) from medicinal and other plants in the control of human
      helminthic diseases. In the search for new anthelmintics among plant
      allelochemicals, 3 practical issues have considerable significance. They are the
      range and capacity of anthelmintic bioassays utilised in preclinical studies in
      vitro on plant extracts, the phenomenon of coexistent allelochemicals with
      overlapping activity spectra within single plants, and the problem of non
      specific cytotoxins among plant allelochemicals. These topics are discussed in
      the context of the present absence of any clinically useful plant anthelmintics.
      In the search for new plant molluscicides for schistosomiasis control, the
      characteristics of a range of molluscicidal plants are measured against those of
      the synthetic molluscicide of choice, niclosamide, and against the postulated
      attributes of practically useful plant molluscicides.

PMID- 9015492
TI  - Compounds with anti-HIV activity from plants.
AB  - Natural products are described which have shown activity against human
      immunodeficiency virus in vitro. These compounds have a variety of chemical
      structures and modes of action. The discovery of these compounds and features of
      their development are used to illustrate aspects of the wider use of natural
      products as novel pharmaceutical agents. Several compounds detailed are being
      tested clinically and may provide new leads for viral chemotherapy. The use of
      extracts with isolated constituents is also discussed.

PMID- 9015493
TI  - Medicinal plants and the control of protozoal disease, with particular reference
      to malaria.
AB  - Malaria and other protozoal diseases continue to pose serious health problems
      world-wide. Resistance of the malaria parasites, Plasmodium spp., to drugs such
      as chloroquine (and, more lately, quinine) occurs with increasing frequency and
      underlies the necessity to develop new agents for malaria chemotherapy; in the
      case of diseases caused by species of Leishmania and Trypanosoma there has always
      been a marked paucity of effective drugs, particularly those with a wide safety
      margin and minimal or no undesirable side effects. Novel drugs, are required to
      help alleviate morbidity and mortality and to contribute to the world-wide
      control of these diseases, in part by helping to reduce the reservoirs of
      infection. Reliance upon plants for the treatment of disease is high in the
      developing world and such plants offer a source of new molecules. Research
      centered upon Plasmodium has produced a number of findings which now prompt the
      formulation of important questions which may influence and focus the direction of
      phytotherapy research in the future.

PMID- 9015494
TI  - Comparison of two methods for assessing child mortality in areas without
      comprehensive registration systems.
AB  - We compared the effectiveness of 2 approaches to assessing child deaths in a
      rural area of Burkina Faso, West Africa. Censuses, repeated yearly, identified
      410 child deaths in the age range 6-59 months. Surveillance using community
      informants identified only 319 deaths. The estimated sensitivities of the 2
      systems were 97% and 76%, respectively. Both systems appeared less effective at
      detecting child deaths before 6 months of age (sensitivities 74% and 57%). Most
      of the deaths missed by the census were of children born since the previous
      census. The cost of one year's surveillance was twice that of a single census.
      The marginal cost of the surveillance system per additional child death
      identified between 6 and 59 months was about US$ 1500. Thorough annual censuses
      may be sufficient to ascertain almost all child deaths over 6 months of age. In
      studies wishing to identify child deaths before 6 months of age, such an approach
      is unlikely to be adequate. In such situations, our data indicated that the use
      of unpaid community informants can improve assessment of deaths. Where accurate
      assessment of early infant death rate is required, regular visits to each
      household by members of the study team are likely to be the only reliable
      approach.

PMID- 9015495
TI  - The interaction between Plasmodium falciparum and P. vivax in children on
      Espiritu Santo island, Vanuatu.
AB  - Studies of the prevalence and incidence of malaria were conducted in children <
      10 years old living in 10 rural villages on the island of Espiritu Santo,
      Vanuatu, south-west Pacific. Malaria prevalence remained stable at 30% throughout
      the year but the relative contributions of the 2 major species were highly
      dependent on season. Plasmodium falciparum predominated in the long wet season
      (November-May) and P. vivax in the dry season (June-October). Case definitions
      for malaria, derived using a multiple logistic regression method, showed that
      parasite densities associated with clinical disease were low; case definitions
      for P. falciparum (> 1000 parasites/microL in children > 1 year old and > 500
      microL in infants) and P. vivax (> 500 parasites/microL at all ages) were both
      associated with a specificity and sensitivity of > 90%. Like prevalence data,
      malaria morbidity was highly seasonal; 80% of clinical P. falciparum infections
      occurred in the wet season and 66% of clinical P. vivax in the dry season. Mixed
      infections were rare. Malaria was important cause of morbidity with children < 5
      years old experiencing 1.3-3.0 episodes of clinical malaria per year and 23% of
      fevers being attributable to malaria in this age group. Children aged 5-9 years
      continued to suffer one episode of clinical malaria per year. The peak incidence
      of P. vivax malaria occurred earlier in life than the peak incidence of P.
      falciparum malaria. The possible interactions between these 2 parasite species
      are discussed.

PMID- 9015496
TI  - Effect of gametocyte sex ratio on infectivity of Plasmodium falciparum to
      Anopheles gambiae.
AB  - Insectary-reared Anopheles gambiae were experimentally fed with the blood of 90
      naturally infected human volunteers carrying gametocytes of Plasmodium
      falciparum. At least one mosquito was successfully infected in 74% of
      experiments. The probability that a gametocyte carrier was infective, the
      probability that a mosquito became infected, and the number of oocysts harboured
      were related to gametocyte density. The mean proportion of male gametocytes was
      0.217 (i.e., 3.6 females for every male). Sex ratios differed significantly
      between gametocyte carriers. Variation in sex ratio was not related to the
      probability that a gametocyte carrier was infective. Among infective people whose
      sex ratio estimates were based on a reasonable number of gametocytes, sex ratio
      significantly predicted the proportion of infected mosquitoes and mean oocyst
      load, with infectivity rising as the proportion of the male gametocytes increased
      towards 50%. There was no indication that infectivity reached a peak at some
      intermediate sex ratio, as would be expected if random mating of gametes was the
      primary determinant of fertilization success. These results raise 2 interesting
      questions: why should higher sex ratios be more infective, and why is the
      observed population sex ratio lower than that which produces the greatest
      infectivity?

PMID- 9015497
TI  - Leishmania infantum and L. major in Algeria.
AB  - Since 1980, the development of leishmaniasis in Algeria has been marked by a
      considerable increase in the number of cases of both visceral leishmaniasis (1121
      cases recorded) and cutaneous leishmaniasis (more than 2000 cases per year). New
      Leishmania infantum and L. major foci have appeared in the north and south of the
      country. During this period, 100 strains of Leishmania isolated from humans,
      other mammals and sandflies have been identified. The presence of L. major MON-25
      in Psammomys obesus and Phlebotomus papatasi had identified these species as the
      main reservoir and vector, respectively, of zoonotic cutaneous leishmaniasis.
      Similarly, the presence of L. infantum MON-1 in Ph. perniciosus and dogs has
      implicated them as the vector and reservoir of visceral leishmaniasis. The
      isolation of the dermotropic zymodeme MON-24 of L. infantum from Ph. perfiliewi
      suggested that it was one of the main vectors of cutaneous leishmaniasis in the
      north of the country; the reservoir has not been identified. In addition, other
      zymodemes of Leishmania have been identified in visceral leishmaniasis patients,
      frequently associated with human immunodeficiency virus (MON-24, MON-33, MON-34
      and MON-78), in patients with cutaneous leishmaniasis (MON-80), and in dogs with
      leishmaniasis (MON-34 and MON-77).

PMID- 9015498
TI  - Predictors for the risk of hookworm infection: experience from endemic villages
      in southern Thailand.
AB  - To assess the role of defaecation pattern in predicting the level of risk for
      hookworm infection in southern Thailand, 4 villages in different geographical
      settings in endemic areas were studied. Close observation and stool examinations
      for hookworm were carried out. The first village was used for exploring the risk
      factors for hookworm infection. The resultant statistical model was then tested
      using the other 3 villages. Only 23-40% of the sample regularly defaecated in a
      latrine. The pattern of defaecation did not differ between the sexes, but was
      associated with age and site of residence. In the first village, the following
      variables were not statistically significant: sex, age, level of past education,
      household income, having neighbouring houses within 20 m, latrine availability,
      site of defaecation. The only statistically significant protective factor was
      shoe wearing, which showed an exposure-outcome severity relationship. Similar
      results were obtained in the other 3 villages. These results refute the
      protective effect of latrine use on the individual user, who may still get
      infection from the faeces of other community members. Promotion of shoe-wearing,
      which provides individual protection, should be an important supplementary
      strategy for hookworm control programmes in such areas.

PMID- 9015499
TI  - Lymphatic filariasis on the coast of Ghana.
AB  - Parasitological, clinical and entomological surveys for lymphatic filariasis were
      carried out in 6 villages and 3 towns on the coast of Ghana. Few or no filarial
      infections were observed in the towns or in the villages east of Accra. However,
      Wuchereria bancrofti microfilaraemia was common in the 4 western villages, with
      overall prevalences of 9.2%-25.4% and overall microfilariae (mf) geometric mean
      intensities of 321-1172 mf/mL of blood. In the same villages, hydrocele affected
      8.5%-27.9% of adult males (aged > or = 20 years), and 5.6%-6.6% of adult
      individuals had elephantiasis (mainly of the legs). In general, the patterns of
      filarial infection and disease in the endemic villages resembled those observed
      in endemic villages in the coastal part of East Africa, with the exception that
      in the Ghanaian focus more females than males were affected by elephantiasis.
      Entomological surveys revealed that Anopheles gambiae s.l. and A. funestus were
      vectors of filariasis in the endemic villages. Only negligible prevalences of
      microfilaraemia were observed in town communities located close to highly endemic
      villages. Control of filariasis in this area is difficult with presently
      available measures, and new control tools, especially development of new drug
      regimens for mass treatment, are greatly needed.

PMID- 9015501
TI  - Transovarial transmission of dengue 3 virus by Aedes aegypti.

PMID- 9015500
TI  - Epidemiology of acute filarial episodes caused by Wuchereria bancrofti infection
      in two rural villages in Tamil, Nadu, south India.
AB  - This year-long study investigated the epidemiology of acute filarial episodes due
      to Wuchereria bancrofti in 2 rural villages in south India. The annual incidence
      of 96.5 episodes/1000 population was significantly higher in males (108.5) than
      females (84.1) an strongly age dependent. First occurrence of acute disease was
      observed in 0.86% of the population, and the average duration of each episode was
      3.6 +/- 2.0 d. Although more than half (63.5%) of the affected individuals
      suffered only 1 episode, a few experienced as many as 8 over the one-year period.
      Individuals with chronic disease were more prone to acute attacks, with 82.9% of
      the total episodes occurring in this group. No seasonal pattern was observed in
      the frequency of episodes. Probit analysis showed that the number of episodes per
      affected person was dependent on sex and chronic condition. Swelling of lymph
      nodes in the inguinal region and fever were the most common symptoms of acute
      disease. The high incidence and resulting debility observed in this study suggest
      that acute episodes are a significant health problem associated with lymphatic
      filariasis. There is clearly a need for more studies on this acute form of
      filarial disease to aid the understanding of the aetiology and epidemiology of
      acute episodes, in planning appropriate control interventions, and in evaluating
      the resulting health burden.

PMID- 9015502
TI  - Possible aetiological role of hepatitis E virus in acute non-A, non-B, non-C
      hepatitis in Saudi Arabia.
AB  - During a period of 10 months, 69 Saudi Arabian patients (14 children and 55
      adults) were diagnosed as having acute non-A, non-B, non-C (NA, B, C) hepatitis
      at King Khalid University Hospital, Riyadh, Saudi Arabia. Seven of the paediatric
      patients had anti-hepatitis E virus (HEV) immunoglobulin (Ig) M and anti-HEV IgG;
      26 adults (47.3%) had anti-HEV IgM and 30 (54.5%) had anti-HEV IgG. These
      results, together with the fact that none of the 40 patients with acute hepatitis
      A virus infection, none of the 24 with hepatitis B virus, and none of the 30 with
      acute hepatitis C virus, had anti-HEV IgM, indicates that HEV is an important
      aetiological agent for acute NA, B, C hepatitis in Saudi Arabia, and that there
      are still other unidentified agent(s) responsible for acute hepatitis in Saudi
      Arabia.

PMID- 9015503
TI  - Acute viral hepatitis in Hanoi, Viet Nam.
AB  - A study of acute hepatitis was conducted in Hanoi, Viet Nam, from January 1993 to
      February 1995; 188 sera from clinical hepatitis cases were screened by enzyme
      linked immunosorbent assay for immunoglobulin (Ig) M anti-hepatitis A virus
      (HAV), IgM anti-hepatitis B core antigen (HBc), IgG anti-hepatitis C virus (HCV),
      IgG anti-hepatitis E virus (HEV) and IgM anti-HEV. Additionally, 187 sera from
      control subjects, matched by age, sex and month of admission, with no recent
      history of hepatitis, were tested for comparative purposes. There was serological
      evidence of recent HAV (29%) and hepatitis B virus (24%) infection in 53% of
      cases (2 mixed infections), compared with 2% of controls. HCV infections were
      detected in 10% of cases (with no IgM anti-HAV or IgM anti-HBc) and in 1% of
      control sera. There was no significant difference in the proportion of IgG anti
      HEV positive sera between cases (in the absence of IgM anti-HAV or IgM anti-HBc)
      (21%) and controls (14%); 3% of all case sera were IgM anti-HEV positive. Younger
      cases (< 20 years) were more likely to have recent HAV infections (41%) than
      those aged > or = 20 years (21%) (P < 0.01). In contrast, a higher percentage of
      adult cases had IgM anti-HBc, IgG anti-HCV and IgG anti-HEV (in the absence of
      recent HAV or HBV infection) than did children. No seasonal trend in hepatitis
      admissions was detected, nor an association between water-borne infections (HAV
      and HEV) and the warmer months. Hepatitis patients lived throughout Hanoi and
      surrounding areas, with no identifiable geographical clustering, regardless of
      serological marker.

PMID- 9015504
TI  - Use of the polymerase chain reaction for detecting Trypanosoma cruzi in
      triatomine vectors.
AB  - Determination of the rate of Trypanosoma cruzi infection in its triatomine
      vectors is an element in control programmes directed at reducing transmission of
      the organism to humans. Traditionally, T. cruzi has been detected in these
      insects by microscopical examination of intestinal contents or excreta. The
      sensitivity of this laborious process has not been defined because of the lack of
      a bench-mark method against which microscopical examination could be compared.
      The purpose of this study was to compare the sensitivity of a polymerase chain
      reaction (PCR) assay with that of microscopical examination for detecting T.
      cruzi in Triatoma infestans nymphs that had fed on patients with chronic Chagas
      disease. To this end, we analysed 54 pairs of samples, each containing 2 groups
      of 10 insects, obtained by feedings on 19 patients with chronic T. cruzi
      infection, 17 of whom were fed upon 3 times. One group of insects in each pair
      was analysed by PCR and the other by microscopical examination of excreta.
      Overall, the PCR assay gave positive results in 32 of 54 groups of insects
      examined (59%), whereas only 7 of 54 groups (13%) were positive by microscopical
      examination (P = 0.038). These results demonstrate that the PCR assay is
      significantly more sensitive for the detection of T. cruzi in triatomine vectors
      than is microscopical examination, and suggest that the PCR assay could be a
      useful tool in epizootiological studies.

PMID- 9015505
TI  - Comparison of Yersinia CIN agar and mouse inoculation assay for the diagnosis of
      plague.

PMID- 9015506
TI  - Molecular forms of adenosine deaminase do not aid the diagnosis of tuberculosis.
AB  - To investigate the diagnostic utility of adenosine deaminase as a test for
      tuberculosis, molecular forms of the enzyme indicative of cell-mediated immunity
      were studied in tuberculosis pleural effusion, peritonitis and meningitis. Twenty
      six pleural, 21 peritoneal, and 24 cerebrospinal tuberculous and non-tuberculous
      fluids were examined for adenosine deaminase and the large and small forms of the
      enzyme were differentiated on immunoblots. Adenosine deaminase levels ranged from
      zero to 81 units/L, zero to 31 units/L and zero to 31 units/L in the pleural,
      peritoneal and cerebrospinal fluids, respectively. The large form of adenosine
      deaminase (280 kDa) was detected in one of 14 proved tuberculous cases, a
      peritoneal fluid. The small form of the enzyme (35-39 kDa) was seen in both
      tuberculous and non-tuberculous conditions in 6 pleural, 7 peritoneal and 8
      cerebrospinal fluids. Molecular forms of adenosine deaminase did not appear to
      help in the diagnosis of tuberculosis in this patient population and may not be
      suited for analysis in fluids with low enzyme activity.

PMID- 9015508
TI  - Clinical overlap between malaria and severe pneumonia in Africa children in
      hospital.
AB  - Data collected from 200 children admitted to a hospital on the Kenyan coast who
      met a broad definition of severe acute respiratory infection (ARI) indicated that
      simple clinical signs alone are unable absolutely to distinguish severe ARI and
      severe malaria. However, laboratory data showed that marked differences exist in
      the pathophysiology of unequivocal malaria and unequivocal ARI. Children in the
      former group had a higher mean oxygen saturation (97 vs. 94, P < 0.001), mean
      blood urea level (5.3 vs. 1.9 mmol/L, P < 0.001) and geometric mean lactate level
      (4.5 vs. 2.1 mmol/L, P < 0.001), and lower mean haemoglobin level (5.3 vs. 9.0
      g/dL, P < 0.001) and base excess (-9.4 vs. -2.6, P < 0.001) than those in the
      latter group. Using these discriminatory variables it was estimated that up to
      45% of children admitted with respiratory signs indicative of severe ARI probably
      had malaria as the primary diagnosis. Radiological examination supported this
      conclusion, indicating that pneumonia characterized by consolidation was uncommon
      in children with respiratory signs and a high malarial parasitaemia (> or =
      10,000/microliters). There is no specific radiological sign of severe malaria. In
      practice, all children with respiratory signs warranting hospital admission in a
      malaria endemic area should be treated for both malaria and ARI unless blood film
      examination excludes malaria. In those with malaria and clinical evidence of
      acidosis, but no crackles, antibodies may be withheld while appropriate treatment
      for dehydration and anaemia is given. However, if clinical improvement is not
      rapid, antibiotics should be started.

PMID- 9015507
TI  - The relationship between glucose production and plasma glucose concentration in
      children with falciparum malaria.
AB  - The pathophysiology of hypoglycaemia in children with acute falciparum malaria, a
      frequent and serious complication, is unknown due to absence of data on glucose
      kinetics. We investigated the correlation between basal glucose production and
      plasma glucose concentration in 20 children (8 girls) with acute, uncomplicated
      falciparum malaria by infusion of [6,6-2H2]glucose. Median plasma glucose
      concentration was 4.5 (range 2.1-6.5) mmol/L and the median glucose production
      5.0 (range 4.1-8.4) mg/kg/min. There was a positive correlation between basal
      glucose production and plasma glucose concentration (r = 0.53, P = 0.016). There
      was no correlation between the rate of glucose production and the plasma
      concentrations of alanine, lactate, counter-regulatory hormones or cytokines. It
      was concluded that, in children with acute uncomplicated falciparum malaria,
      endogenous glucose production is an important determinant of plasma glucose
      concentration, contrary to previous findings in adults with malaria, in whom
      peripheral uptake seems to be more important than glucose production in
      determining plasma glucose concentration.

PMID- 9015509
TI  - Pulmonary hypertension in schistosomiasis mansoni.
AB  - To evaluate cardiopulmonary involvement in schistosomiasis mansoni, 246 patients
      from an endemic area of Brazil were examined; 152 had been previously treated for
      schistosomiasis. Based on stool examination and/or abdominal ultrasonography, the
      patients were divided into those with schistosomiasis (69%) and those in whom the
      disease was not present (31%). M mode measurements were similar in the 2 groups.
      Pulmonary pressure was measured by Doppler echocardiography; 25% of the subjects
      had pulmonary hypertension. Those with pulmonary hypertension had a higher
      prevalence of schistosomiasis (80%) than those without (64%; P = 0.03). No case
      of cor pulmonale was diagnosed by electrocardiography or Doppler
      echocardiography. The prevalence of pulmonary hypertension correlated neither
      with periportal fibrosis nor with prior treatment for schistosomiasis.

PMID- 9015511
TI  - Impact of lymphatic filariasis on the productivity of male weavers in a south
      Indian village.

PMID- 9015510
TI  - Effect of intestinal helminthiasis on intestinal permeability of early primary
      schoolchildren.
AB  - Intestinal permeability of 246 early primary schoolchildren at 2 schools (106 of
      whom were infected with intestinal helminths) was assessed by using the
      lactulose/mannitol differential absorption test. The ratio of the urinary
      recoveries of lactulose and mannitol was determined after oral administration of
      a standard solution of the 2 sugars. Assessment of intestinal permeability was
      repeated on 100 infected children after treatment and on a cohort of 68
      uninfected children. Infected and uninfected groups were compared with respect to
      baseline lactulose/mannitol ratio (L/M1) and change in lactulose/mannitol ratio
      between assessments (delta L/M). The correlations between baseline intensity of
      infection and L/M1, and between fall in intensity and delta L/M, were evaluated.
      Based on a crude index of socioeconomic status, each child was assigned to one of
      3 socioeconomic groups; all but 3 children belonged to either groups 2 or 3.
      Trichuris trichiura and Ascaris lumbricoides were the 2 predominant infections;
      the hookworm infection rate was relatively low. The results suggested that
      helminthiasis exerted only a marginal effect on intestinal permeability, the
      impact of which in children from lower socioeconomic backgrounds was negligible
      in comparison with the cumulative effects of other factors.

PMID- 9015512
TI  - Skin changes in chronic lymphatic filariasis.
AB  - Seventeen men and 31 women with unilateral lower limb lymphoedema attributed to
      chronic lymphatic filariasis were examined in the filarial out-patient clinic of
      the Government General Hospital, Madras, India. Skin changes such as skin fold
      thickening, hyperkeratosis, hypo- or hypertrichosis, pachydermia, pigmentary
      changes, chronic ulceration, epidermal and sub-epidermal nodules, and clinical
      intertrigo were observed and compared between the different lymphoedema grades.
      These lesions are not specific to chronic lymphatic filariasis, and have been
      described in other conditions displaying lymphostasis. They are thought to be
      favoured by secondary infections, which should be dealt with appropriately to
      prevent the progression of the disease and the onset of elephantiasis.

PMID- 9015513
TI  - Pathological fracture in mycetoma.

PMID- 9015514
TI  - Mycetoma-induced palatal deficiency and pharyngeal plexus dysfunction.

PMID- 9015515
TI  - Direct evidence that asparagine at position 108 of the Plasmodium falciparum
      dihydrofolate reductase is involved in resistance to antifolate drugs in
      Tanzania.
AB  - A nested polymerase chain reaction was used to amplify a fragment of the gene for
      dihydrofolate reductase of Plasmodium falciparum containing codon 108, where a
      point mutation, causing a serine to asparagine change, occurs in pyrimethamine
      resistant parasites. The presence of the mutation was detected by restriction
      enzyme digestion. Parasites in blood samples collected from asymptomatic children
      before, and 3 weeks after, treatment with pyrimethamine-sulfadoxine or
      chlorproguanil-dapsone were analysed. Parasites in the samples taken at 3 weeks
      carried only the asparagine mutant.

PMID- 9015516
TI  - The risk of malaria in travellers to Thailand.

PMID- 9015517
TI  - Atovaquone plus proguanil is an effective treatment for Plasmodium ovale and P.
      malariae malaria.

PMID- 9015518
TI  - Skin depigmentation due to antimalarial prophylaxis with chloroquine.

PMID- 9015519
TI  - Prolonged clearance of microfilaraemia in patients with bancroftian filariasis
      after multiple high doses of ivermectin or diethylcarbamazine.
AB  - In a double-blind trial on 37 asymptomatic microfilaraemic subjects (minimum 400
      microfilariae [mf] per mL) with Wuchereria bancrofti infection, the safety,
      tolerability and macrofilaricidal efficacy of 12 fortnightly doses of ivermectin,
      400 micrograms/kg (ivermectin group), was compared with 12 fortnightly doses of
      diethylcarbamazine (DEC), 10 mg/kg (DEC group), over a period of 129 weeks after
      treatment. A control group (LDIC group) was treated with low dose ivermectin to
      clear microfilaraemia, for ethical reasons. Both ivermectin and DEC in high
      multiple doses were well tolerated and clinically safe. Macrofilaricidal efficacy
      was assessed by prolonged clearance of microfilaraemia, appearance of local
      lesions, and reduction of circulating W. bancrofti adult antigen detected by an
      antigen capture enzyme-linked immunoassay based on the monoclonal antibody AD12.
      Mf counts fell more rapidly after ivermectin than after DEC, but low residual mf
      levels were equivalent in these groups after week 4. Conversely, filarial antigen
      levels fell more rapidly after DEC than after ivermectin, but low residual
      antigen levels in these groups were statistically equivalent at all times beyond
      12 weeks. Mild, self-limited systemic reactions to therapy were observed in all 3
      treatment groups. Local reactions, such as development of scrotal nodules, were
      observed in several subjects in the DEC and ivermectin groups. These results
      suggested that high dose ivermectin and DEC both had significant macrofilaricidal
      activity against W. bancrofti, but neither of these intensive therapeutic
      regimens consistently produced complete cures. Thus, new drugs or dosing
      schedules are needed to achieve the goal of killing all filarial parasites in the
      majority of patients.

PMID- 9015520
TI  - Control of bancroftian filariasis in an endemic area of Polynesia by ivermectin
      400 micrograms/kg.
AB  - Community treatment with ivermectin was implemented in Opoa, French Polynesia
      from April 1991 to October 1993. All consenting inhabitants aged 3 years or more
      were treated with twice-yearly single doses of ivermectin, pregnant women
      excepted. A dosage of 100 microgram/kg was used for the 3 first treatments and
      then abandoned because it did not reduce the prevalence of microfilariae (mf)
      carriers. With a dosage of 400 micrograms/kg dosage, this prevalence decreased
      dramatically from 21% to 7%, and the mf level in carriers dropped to only 0.5% of
      its initial value after 3 treatments. The 400 micrograms/kg dosage was well
      tolerated and compliance was excellent. The twice-yearly single dose strategy
      with ivermectin at 400 micrograms/kg is safe and highly effective for filariasis
      control in an endemic area.

PMID- 9015522
TI  - A randomized double-blind clinical trial of two antivenoms in patients bitten by
      Bothrops atrox in Colombia. The Regional Group on Antivenom Therapy Research
      (REGATHER).
AB  - A randomized double-blind clinical trial in 39 patients envenomed by Bothrops
      atrox in Antioquia and Choco, Colombia, was performed to compare the efficacy and
      safety of 2 equine-derived antivenoms prepared at Instituto Clodomiro Picado,
      University of Costa Rica. Twenty patients received a monovalent anti-B. atrox
      antivenom (group A) and 19 patients were treated with a polyvalent (Crotalinae)
      antivenom (group B). Both antivenoms were equally efficient in the neutralization
      of the most relevant signs of envenoming (haemorrhage and blood clotting time
      alteration). Fourteen patients (36%) presented early adverse reactions to
      antivenoms and no significant difference between the 2 groups was observed.
      Urticaria (18%) was the most frequent early adverse reaction and there was no
      life-threatening anaphylactic reaction. Based on clinical criteria and serum
      venom levels, estimated by an enzyme immunoassay, 15 patients were classified
      into 2 groups: mild and moderate/severe envenoming. With the antivenom doses used
      in this study (3, 6 and 9 vials for mild, moderate and severe envenoming,
      respectively), both antivenoms were equally efficient in clearing serum venom
      levels within the first hour of treatment, and the levels remained below the
      lower limit of venom detection for 24 h. Antivenom concentration in serum
      remained high for up to 24 h after antivenom infusion, suggesting that an excess
      of antibody in relation to circulating antigen had been administered.

PMID- 9015521
TI  - Resistance to antituberculosis drugs in rural South Africa: rates, patterns,
      risks, and transmission dynamics.
AB  - This study describes the rate, pattern, and transmission dynamics of, and risk
      factors for, isolates of Mycobacterium tuberculosis resistant to antituberculosis
      drugs in a rural South African health district. Twenty-one of 254 (7.6%; 95%
      confidence interval [CI] 4.8-11.4) isolates from incident cases were resistant to
      at least one drug (isoniazid, rifampicin, streptomycin, ethambutol). A random
      sample of 28 otherwise susceptible isolates and all 21 resistant isolates were
      susceptible to pyrazinamide. There was one case of combined isoniazid/rifampicin
      resistance. The rate of initial resistance was 8.1% (95% CI 4.9-12.4) and of
      acquired resistance 6.2% (95% CI 1.9-14.2). Age, sex, known human
      immunodeficiency virus status, and previous treatment history were not associated
      with drug resistance. Restriction fragment length polymorphism (RFLP) analysis of
      13 of the 21 resistant specimens showed 12 different banding patterns. Rates of
      drug resistance were low in this representative sample of patients from a defined
      geographical area. Previous treatment history was probably not a risk factor
      because of the use of multiple drug regimens, directly observed therapy, and high
      completion rates in those previously treated. Although limited in number, the
      RFLP data suggested that recent local transmission of resistant strains was not
      occurring to a significant extent.

PMID- 9015523
TI  - High prevalence of the third form of merozoite surface protein-1 in Plasmodium
      falciparum in asymptomatic children in Gabon.

PMID- 9015524
TI  - Parasite-specific serum IgG following successful treatment of endemic
      strongyloidiasis using ivermectin.

PMID- 9015525
TI  - Extensive genetic diversity of Plasmodium falciparum isolates collected from
      patients with severe malaria in Dakar, Senegal.
AB  - While some genetic host factors are known to protect against severe Plasmodium
      falciparum malaria, little is known about parasite virulence factors. We have
      compared the genetic characteristics of P. falciparum isolates collected from 56
      severe malaria patients and from 30 mild malaria patients recruited in Hopital
      Principal, Dakar, Senegal. All isolates were typed using polymerase chain
      reaction amplification of polymorphic genetic loci (MSP-1, MSP-2, HRP1, GLURP,
      CSP, RESA, and the multigene family Pf60). The complexity of infections was lower
      in severe than in mild malaria and the parasite genetic diversity in both groups
      was very large. No specific genetic make-up was associated with severity; there
      were, however, marked differences in allele frequencies in both groups, with a
      prevalence up to 60% of MSP-2 alleles specifically observed in the severe malaria
      isolates. In addition, the presence of MSP-1/RO33 alleles was significantly
      associated with a higher plasma level of tumour necrosis factor alpha receptor 1
      (P < 0.05), a reported indicator of severity in human malaria. These results
      point to potential differences in the genetic characteristics of parasites
      inducing severe versus mild pathology.

PMID- 9015526
TI  - Molecular typing of multi-drug resistant Shigella dysenteriae type 1 by plasmid
      analysis and pulsed-field gel electrophoresis.
AB  - Recently, an outbreak of dysentery due to multi-drug resistant Shigella
      dysenteriae type 1 strains was reported along the coastal area of Kenya and
      shortly thereafter another outbreak appeared in the outskirts of Nairobi. We
      analysed 22 multi-drug resistant S. Dysenteriae type 1 strains isolated from
      cases in the latter outbreak using plasmid deoxyribonucleic acid (DNA) profiles
      and pulse-field gel electrophoresis of genomic DNA. All isolates were resistant
      to commonly available drugs including ampicillin, trimethoprim,
      sulphamethoxazole, chloramphenicol, tetracycline and streptomycin with minimum
      inhibitory concentrations > 64 micrograms/mL, but were fully sensitive to
      gentamicin. Only 2 strains were resistant to nalidixic acid. Analysis of plasmid
      DNA and genomic DNA revealed that all 22 strains were clonally related. It is
      likely that the present outbreak was related to that on the coast, as suggested
      by the similarity in drug susceptibility data. The drug susceptibility and
      molecular epidemiological data provide a useful baseline for future monitoring of
      epidemic and endemic S. dysenteriae activity in East Africa.

PMID- 9015527
TI  - George Busk, FRS (1807-1886): surgeon, zoologist, parasitologist and
      palaeontologist.

PMID- 9015528
TI  - O come, let us wallow in glorious mud.

PMID- 9015529
TI  - When injections are not necessary.

PMID- 9015530
TI  - The ParaSight-F test.

PMID- 9015532
TI  - Endoscope-assisted intraoral approach for masseteric hypertrophy.
AB  - Although conventional intraoral surgery for masseteric hypertrophy is a useful
      technique, it is considerably difficult to resect the mandibular angle due to the
      narrow visual field. For the purpose of compensating for the drawbacks of this
      procedure, we performed endoscope-assisted intraoral surgery on 5 patients with
      bilateral masseteric hypertrophy, who were successfully treated. The use of an
      endoscope offers a clear view of the mandibular angle region, thus facilitating
      accurate and easy resection of the spur.

PMID- 9015531
TI  - Endoscopic pediatric plastic surgery.
AB  - Although the advent of endoscopic technology is expanding the fields of
      reconstructive and aesthetic surgery in adults, there have been to date no
      reports of its use in the pediatric population. Because of its minimally invasive
      nature, yet wide range of exposure, endoscopic techniques have much appeal in
      this age group. Herein we present our initial experience with endoscopic
      pediatric plastic surgery. From February 1995 to December 1995, 41 patients were
      treated utilizing 5-mm and 10-mm endoscopes at Scottish Rite Children's Medical
      Center, Atlanta, GA. There were 19 males and 22 females. The mean age at surgery
      was 5.6 years (range, 7 months-15 years). The most common types of procedures
      performed were insertion of tissue expanders (N = 19), excision of facial
      dermoids (N = 7), torticollis release (N = 5), and excision of vascular lesions
      (N = 4). The remaining 6 patients underwent a variety of reconstructive
      procedures. The complication rate in the tissue expander group was 3 out of 39
      expanders inserted (9.5%), and consisted of infection (N = 2) and rupture (N =
      1). In the dermoid group, complications consisted of wound infection requiring
      reoperation (N = 1), and transient frontal paresis (N = 1). One patient in the
      hemangioma group had an incomplete resection necessitating open excision. The
      remaining patients all had satisfactory outcomes with no complications. The
      majority of the procedures were done on an outpatient basis. These results
      suggest that endoscopic techniques are eminently applicable in the pediatric
      population, providing the benefits of small and remote incisional wounds with
      complication rates that are comparable to those of conventional surgical
      treatment.

PMID- 9015533
TI  - Reconstruction of head and neck hemangiomas with tissue expansion in the
      pediatric population.
AB  - A retrospective study of 245 patients with 299 hemangiomas treated from May 1981
      to April 1994 was done. A subset of 175 of these patients (58.5%) had hemangiomas
      of the head and neck. Six of the 175 (3%) required reconstruction following laser
      therapy. Tissue expansion was chosen for each of these reconstructions. Five
      females and 1 male underwent tissue expansion. The age of the patients at the
      time of tissue expansion ranged from 2.5 to 12 years, with an average of 6 years.
      Tissue expander sizes were 50 cc and 100 cc. Infection was seen during the course
      of expansion in 1 patient. Satisfactory results were achieved after
      reconstruction in all cases. Tissue expansion is the treatment of choice for
      reconstruction of head and neck hemangioma deformities following laser or other
      surgical procedures as well as involution.

PMID- 9015534
TI  - Sensory reinnervation of autologous tissue TRAM flaps after breast
      reconstruction.
AB  - The use of the transverse rectus abdominis musculocutaneous (TRAM) flap has come
      to the forefront for breast reconstruction following mastectomy. Despite our
      ability to create surgically a supple breast mound, simulate the nipple with
      local skin flaps, and pigment the skin to create an areola, one of the last
      drawbacks has been the reestablishment of normal sensation. Some patients have
      anecdotally reported some sensory return in the reconstructed breast mound. We
      sought to quantitate the pattern of sensory return in TRAM flaps in 24 patients
      to identify factors that favor sensory reinnervation of the flap. Patients were
      recalled for sensory testing after unilateral or bilateral breast reconstruction
      following mastectomy for cancer or premalignant mastopathy. The interval from
      surgery varied from 3 to 41 months. Sensation was evaluated using the Semmes
      Weinstein monofilament test, hot/cold recognition, and vibratory sensation
      measured in 16 segments of the reconstructed breast mound and compared to the
      opposite, unoperated breast or to volunteer controls. Thirty-four flaps were
      evaluated. The Semmes-Weinstein measurements demonstrated measurable sensation in
      32 of 34 flaps with 2 flaps developing sensation equal to the control unoperated
      breast. The return of hot recognition occurred in 21 of 34 flaps, cold
      recognition in 22 of 34 flaps, and vibratory sensation in 26 of 34 flaps. Our
      findings suggest that excellent sensory return occurs in the majority of patients
      via nerve ingrowth into the flap from the mastectomy bed. It would appear that a
      natural breast reconstruction with some sensation can be a reality for the
      majority of patients in the absence of additional complex surgical maneuvers such
      as nerve preservation or nerve-nerve coaptation.

PMID- 9015535
TI  - Magnetic resonance imaging of the TRAM flap donor site.
AB  - High-field magnetic resonance imaging (Magnetom 42 SP, 1.0 Tesla) was performed a
      mean of 22 months (range, 8-42 months) postoperatively on 29 women who had
      undergone unilateral breast reconstruction with a transverse rectus abdominis
      musculocutaneous (TRAM) flap (19 free and 10 pedicled TRAM flaps). Fifteen T1
      weighed, cross-sectional spin-echo images of the abdominal wall were obtained
      using a surface coil. The free TRAM flap was elevated sparing the lateral third
      of the rectus muscle. In the pedicled TRAM flap the whole rectus muscle was used.
      The patient groups were demographically similar, with no statistical differences
      in age or body mass index. In the free TRAM group the mean (+/-standard
      deviation) area of the rectus muscle in the upper third of the muscle (first five
      slices) was smaller on the operated side (376 +/- 135 mm2) than on the
      contralateral side (462 +/- 78 mm2), p = 0.02. The mean signal intensity
      (reflecting intramuscular fat content) of the upper third of the muscle was
      significantly higher on the operated side than on the nonoperated side, p = 0.04.
      Intramuscular fat content was also estimated and graded using an arbitrary scale
      from 1 to 4. The fat content of the upper third of the muscle was graded higher
      on the donor side (median, 3) than on the contralateral side (median, 2), p <
      0.01. In pedicled TRAM flap patients, the remaining rectus was responsible for a
      mean of 47 +/- 5% of the distance between the lateral muscles, leaving a mean of
      63 +/- 10 mm of the abdominal wall covered by fascia only. No hernias were
      detected in either group. This study shows that harvesting of a free TRAM flap
      seems to affect the quality of the donor rectus muscle over its whole length.

PMID- 9015536
TI  - One-stage reconstruction for defects caused by cancrum oris (noma).
AB  - Cancrum oris is a disease process that has been described for centuries, but now
      presents primarily in developing countries. The disease in known to occur in
      association with poor nutrition and exanthematous infections. The acute disease
      occurs usually in young children, and the infectious process causes destruction
      of the involved orofacial tissues with variable degrees of tissue loss and scar
      reaction in those who are affected and survive. The chronic sequelae of the acute
      disease process often require reconstructive surgery. We present the natural
      history of the disease process and its causes, and demonstrate the wide spectrum
      of resulting defects that challenge the reconstructive surgeon. Because of the
      socioeconomic situation inherent with these patients and the volume of patients
      in need of treatment with this disease, innovative and efficient treatment is
      required. We have demonstrated methods of reconstructive surgery that differ from
      the multiple staged procedures described in previous studies by allowing for one
      stage surgical reconstruction of even the most complex cases. This allows for
      treatment of the majority of patients in their native countries in a cost
      effective and safe manner, and treatment of more severely afflicted individuals
      in modern medical centers without their having to spend a long time period away
      from their homes.

PMID- 9015537
TI  - Homodigital neurovascular island flaps with "direct flow" vascularization.
AB  - Pulp loss of the fingers is frequently observed. When local advancement flaps are
      not sufficient to repair the defect, the homodigital monopedicled island flaps
      with "direct flow" are a simple and current reconstructive solution. Between 1991
      and 1995, 32 homodigital neurovascular direct flow island flaps were performed
      for fingertip defects. We used a modified triangular Venkataswami flap for
      oblique amputations (26 patients) and the Mouchet-Gilbert island flap for
      tangential defects (6 patients). Our results (with excellent skin quality and
      good sensory recovery) lead us to consider these flaps as the first-choice
      reconstructive solution in patients with extensive but not complete pulp defects
      (< 2 cm) of the fingers.

PMID- 9015538
TI  - Sliding shape-designed latissimus dorsi flap.
AB  - The latissimus dorsi musculocutaneous flap can provide a large, reliable flap for
      reconstruction of various areas of the body. This flap can also be extended quite
      some way over the anterior and upper border of the muscle, although its width is
      limited to between 10 cm and 12 cm if direct closure of the donor site defect is
      required. This paper presents a sliding-shaped modification of the latissimus
      dorsi flap that enables the flap to be used efficiently in covering a wide defect
      as well as in correcting the donor site defect.

PMID- 9015539
TI  - What you see is what you get: lack of significant postoperative contour change in
      muscle transplants to the lower leg.
AB  - A widely held tenet in the reconstructive surgery literature is that muscle
      transplants undergo significant postoperative atrophy, contributing to
      progressive improvement in appearance of the reconstruction. In contrast, it has
      been our experience that muscle transplants retain the majority of their bulk
      following inset, and undergo minimal postoperative atrophy. Prospective
      evaluation of 20 patients undergoing muscle transplant reconstruction of Gustillo
      type IIIB lower limb wounds found minimal decrease in limb circumference at 6
      month follow-up, as measured at the point of maximum transplant projection.

PMID- 9015540
TI  - Anatomic study of the dorsalis pedis-first dorsal metatarsal artery.
AB  - The vascular anatomy of the dorsalis pedis-first dorsal metatarsal artery was
      investigated with regard to its general distribution and variation. We especially
      focused on the status of the dorsalis pedis-first dorsal metatarsal-first plantar
      metatarsal arterial interconnection and the sagittal course of the first dorsal
      metatarsal artery in order to get information for operating procedures and to
      understand the vascular reliability of the flap. Thirty-two feet of 17 Caucasian
      fixed cadavers were dissected after injection of dye or resin into the popliteal
      artery. The first dorsal metatarsal artery was always present. It arose from the
      dorsalis pedis artery in 90.6% of cases and from the lateral tarsal artery in
      9.4% of cases. The critical point, where the first dorsal metatarsal artery (or
      the first plantar metatarsal artery in cases when the former branched from the
      latter) was located 10 mm distal to the tarsal-first metatarsal joint and 5.5 mm
      plantar from the dorsal surface of the second metatarsal bone. The medial head of
      the first dorsal interosseous muscle crossed dorsal to the first dorsal
      metatarsal artery in 31.2% of cases. The first dorsal metatarsal artery coursed
      superficial to the first dorsal interosseous muscle (59.4%), was partially
      embedded with the muscle (18.8%), or coursed along the bottom of it or below it
      (21.9%). In the latter type, 4 out of 7 specimens showed the thin arterial loop.
      The arterial network in the first interosseous space presented several anatomic
      variations. The standard pattern (group I) was most frequent (71.9%). Other
      variations (group II) could be further categorized into four subdivisions
      according to the pattern of the arterial interconnection.

PMID- 9015541
TI  - A technique to investigate mural thrombus formation in small arteries and veins:
      I. Comparative morphometric and histological analysis.
AB  - Numerous clinically relevant animal models exist for thrombosis studies. Few of
      these are suitable for both arteries and veins. In this investigation, an
      established venous thrombosis model was adapted through minimal technical
      adjustments to allow also the study of arterial thrombosis. A standardized
      subintimal crush injury was performed to carotid arteries or femoral veins of
      hamsters. Thrombus volumes were then quantified by direct morphometric
      measurements from serial microscopic sections or by on-line image analysis of
      light intensity changes from transilluminated vessels. The platelet-rich mural
      thrombus, which was established within minutes of the trauma, disintegrated
      during the observation period. The life cycle of the thrombus was different in
      arteries and veins, but significant linear correlation (p < 0.01) was found in
      both types of vessel between thrombus volumes measured by the two techniques. The
      model can consequently be used for comparative in vivo thrombosis studies in
      small (approximately 1-mm) arteries and veins.

PMID- 9015543
TI  - Repair of an untreated cleft palate in an adult using a prefabricated radial
      forearm flap.
AB  - The untreated isolated cleft of the palate in an adult is rarely encountered
      today. It can also be difficult to close using conventional techniques because of
      the disparity between the extremely wide cleft and the paucity of available local
      tissues. One possible solution is a thin radial forearm free flap. If used as a
      bilaminar flap prefabricated by placement of a skin graft on its fascial
      undersurface at an initial stage, both the requisite nasal lining and oral mucosa
      can simultaneously be introduced to close the palate. This maneuver may reduce
      the potential for late flap contracture and avoids cumbersome methods for
      immobilizing a skin graft if this were attempted after flap transfer.

PMID- 9015542
TI  - A technique to investigate microvascular mural thrombus formation in arteries and
      veins: II. Effects of aspirin, heparin, r-hirudin, and G-4120.
AB  - After a standardized trauma to carotid arteries or femoral veins of hamsters, the
      antithrombotic effects of two antiplatelet agents (aspirin and the glycoprotein
      IIb/IIIa antagonist G4120) and two anticoagulants (heparin and the direct
      thrombin inhibitor r-hirudin) were studied in vivo. The thrombus area volume was
      assessed by image analysis of the transilluminated experimental vessels. Heparin,
      r-hirudin, and G-4120 demonstrated a dose-dependent complete inhibition of
      arterial and venous thrombosis. In contrast, the antithrombotic effect of aspirin
      was only partial in both vessel types. A significant correlation between
      activated partial thromboplastin time (aPTT) at the end of the experiments and
      the antithrombotic effect was observed with the anticoagulant agents. However,
      only r-hirudin inhibited thrombus formation at a therapeutical prolongation of
      aPTT, while heparin required supratherapeutical amounts to achieve the same
      inhibition. The data confirm that the inhibition of aspirin, heparin, r-hirudin,
      and G-4120 on the formation of platelet-rich thrombi is independent of the blood
      flow rate.

PMID- 9015544
TI  - Case report: upper extremity soft-tissue reconstruction by alloplastic implant:
      long-term result and follow-up.
AB  - Prosthetic implants for reconstruction have found a variety of applications. Soft
      tissue defects of the extremities are but one example in which alloplastic
      reconstruction is useful. As shown in the following case, gratifying cosmetic
      results can be obtained in posttraumatic upper extremity defects by
      reconstruction with a silastic implant. Although it is not a novel use for the
      device, it is one that has not been widely reported. The patient has been
      followed for 7 years postoperatively and he remains pleased with the cosmetic
      result. Furthermore, his function has not been compromised by placement of the
      prosthesis.

PMID- 9015545
TI  - A case of Ollier's disease of the hand.
AB  - Enchondroma is a benign growth of cartilage arising in the bone metaphysis as a
      solitary or multiple primary lesions. The form of multiple enchondromatosis with
      unilateral predominance is termed Ollier's disease. We have recently treated a
      case of Ollier's disease with the chief complaint of deformity of the left hand.
      The patient was an 11-year-old boy. Radiographic examination showed honeycombed
      clear spaces in the metaphyses of the middle and proximal phalanges of the left
      ring and little fingers as well as of the fourth and fifth metacarpals, and
      thinning of the cortex of these bones, but with no evidence of pathological
      fracture. The tumors of the left fourth and fifth metacarpal bones and of the
      phalanges of the left ring and little fingers were removed, and the
      metacarpophalangeal joint of the little finger was capsulotomized. The patient
      was free from recurrence 19 months after surgery. With regard to the prognosis of
      Ollier's disease, malignant transformation into chondrosarcoma or osteosarcoma
      has been reported of the chondroma. Since Ollier's disease is self-limited in
      that it usually stops spontaneously as the patient grows, and since the
      cartilaginous lesions in occasional cases may regress or even disappear, any
      cartilaginous lesions that are still active or painful after termination of the
      growth period should be examined thoroughly under suspicion of undergoing
      malignant transformation.

PMID- 9015546
TI  - Generalizations from a generalist journal.

PMID- 9015547
TI  - Re: High-energy gunshot wounds to the face.

PMID- 9015548
TI  - The age of microspecialization: is there an epidermist in the house?

PMID- 9015549
TI  - Methicillin-resistant Staphylococcus aureus infection in hospital staff.

PMID- 9015550
TI  - Schwannoma presenting as a nasal tip deformity.

PMID- 9015551
TI  - Re: Midpalmar approach to the carpal tunnel: an alternative to endoscopic
      release.

PMID- 9015553
TI  - Re: Is blood transfusion necessary in reduction mammaplasty patients?

PMID- 9015552
TI  - Relapsing polychondritis.

PMID- 9015554
TI  - Re: Evaluations of aesthetic results in breast reconstruction: an analysis of
      reliability.

PMID- 9015555
TI  - Reconstruction of deep ulcer by free groin flap transfer.

PMID- 9015557
TI  - Influences on meat avoidance among British students.
AB  - Male and female undergraduates (18-23 years old; 68% in their first year; N =
      158) who had just chosen a vegetarian dish in a campus dining hall or restaurant
      reported a diversity of meat avoidance habits before arrival at University a few
      weeks previously. More women than men had avoided meat and other flesh foods,
      with the exception of fish. Consistently with the distinction between "red" and
      "white" meats, chicken and turkey were the least often avoided flesh foods among
      men and women. The only clear gradation from flesh-eating to vegetarianism was
      eating poultry and either beef/lamb or pork, eating only poultry and eating
      neither; fish was not on this Guttman scale, contrary to previous assumptions.
      Reasons for avoiding meat and perceived influences on preferences for food in
      their chosen vegetarian dish were elicited by open-ended interviews in 41 women
      from the meat-avoidance survey. Rationales spontaneously offered were as diverse
      as reported in previous studies, but always included at least two of the
      following: ethics of raising/killing animals, concern for health, sensory
      factors, disgust and influence of friends. In contrast, choices among described
      variants of the familiar dish were largely controlled by its sensory and
      nutritional features, presumably because other attributes had been factored out.

PMID- 9015558
TI  - Toward an understanding of laypeople's notions about additives in food: clear-cut
      viewpoints about additives decrease with education.
AB  - The focus of this article is on laypeople's notions about additives in food. A
      dilemma embodying the basic controversial standpoints on additives was given in
      interviews with 145 young and middle-aged adults representing different
      educational levels and fields during the years 1986-1988. The least and most
      educated subjects were interviewed again during 1993-1994 (N = 62). Interviewee
      standpoints and their justifications for them were probed in semi-structured
      interviews. The emergent attitudes could be located in four categories: Harmful,
      Safe, Both and Neither. There was a general movement from the clear-cut Harmful
      and Safe to Both and Neither, a trend which was not brought about by the
      selective sampling of interviewees for the follow-up study. In general, the more
      education the respondents had, the more often they expressed the standpoints Both
      and Neither and vice versa. Further education seems to soften the expression of
      straight for-or-against standpoints, as well as most misunderstandings about
      additives. Higher education helps people not only to simultaneously hold
      contradicting perspectives in mind, but also to analyse and integrate these
      perspectives, which is quite necessary in understanding open questions and in
      coping with insecurity in a modern society.

PMID- 9015559
TI  - High resting energy expenditure in normal-weight bulimics and its normalization
      with control of eating behaviour.
AB  - Resting energy expenditure (REE) has been found to be lower in normal weight
      bulimics (NWBs) than in controls and it was speculated that metabolic
      abnormalities might underlie bulimia. This study consisted of a longitudinal
      assessment of REE, body composition and energy intake before, during and after
      the control of eating behaviour, with comparisons between REEs in NWBs, those in
      controls, and estimated basal energy expenditure (EBEE). NWBs in acute phase of
      bulimia were assessed the 1st, 2nd, and last day of a one-week hospitalization
      that warranted compliance with normal diet. Assessments were then repeated after
      a six-week outpatient psychotherapy. Mean REE in NWBs was higher than that in
      controls and EBEE on admission. It decreased down to normal rate at discharge and
      at therapy termination. Fat-free mass (FFM) decreases slightly during
      hospitalization despite a weight-maintenance diet, but REE-FFM ratio also
      decreased significantly. Metabolic factors which might account for these results
      are discussed. Data suggest that: (1) caloric requirements in NWBs were higher
      than estimated weight-maintenance rations; (2) binge-eating increased REE; (3)
      control of eating behaviour decreased REE.

PMID- 9015560
TI  - Observational conditioning of food valence in humans.
AB  - It has been suggested that the observation of a model consuming a food (CS) and
      facially expressing either to like or to dislike (US') the food, may be a
      sufficient condition to bring about a change in the valence of the food for the
      observer. Unfortunately, up to now this hypothesis has not been investigated in a
      straightforward manner. In this study, during acquisition, children consumed a
      series of evaluatively neutral colored and flavored drinks, while simultaneously
      they watched a videotaped model synchronically drinking identical drinks and
      facially expressing his evaluation (neutral or dislike) of the liquids. In one
      condition, the presence of a particular flavor in the drinks was designated to
      function as the CS+ or the CS-, whereas in the other condition it was the color
      of the drinks which was the critical CS+ or CS-. Next, the children evaluated a
      series of drinks containing the critical CSs. A clear evaluative learning effect
      was obtained when the flavor but not when the color of the drinks was
      systematically paired with the model's facial expression of dislike. Moreover,
      the flavor conditioning effect was dependent on the presence in the test drinks
      of the local context cues (c.q. the colors of the drinks) which were used during
      acquisition. Finally a double dissociation was observed between explicit beliefs
      and the "evaluative knowledge" expressed in the ratings of the drinks, in that
      none of the children in the CS = Flavor groups evidenced any explicit knowledge
      about the crucial CS-US' contingency but showed evaluative conditioning, whereas
      the majority of the children in CS = Color groups were aware of the CS-US'
      relation but failed to demonstrate an evaluative CS-/CS-differentiation.

PMID- 9015561
TI  - Ponderostat: hoarding behavior satisfies the condition for a lipostat in the rat.
AB  - The mass of food hoarded by rats given access to food only two hours per day is
      proportional to the rats' body weight deficit. The present work investigated
      whether this behavior might reflect the amount of body fat rather than body
      weight. The hoarding behavior of three rats was measured every other day at
      various body weights. After each hoarding session the animals were anesthetized
      and their percentage of fat was measured in vivo with a total body electrical
      conductivity method (TOBEC). The results showed that the amount of food hoarded
      in the two-hour sessions was inversely proportional to the fat content of the
      body. This result shows that, in the rat, the fat stored is correlated with the
      behavioral response leading to the defence of body weight, and therefore
      satisfies a condition necessary for a lipostat.

PMID- 9015562
TI  - An immunohistochemical study of HLA-DR and alpha 1-antichymotrypsin-positive
      cells in the pulp of human non-carious and carious teeth.
AB  - The condition of the pulp tissue was classified into seven groups according to
      the progression of carious lesions from stages S0 (non-carious teeth) to S6
      (exposed pulp). There was a small number of anti-HLA-DR antibody-positive cells
      in the pulp of the early carious teeth, and a markedly increased number at S5 and
      S6. The recruitment of a large number of anti-HLA-DR cells concomitant with a
      marked increase of other kinds of immunocompetent cells in the pulp of late-stage
      caries might indicate the occurrence of antigen presentation followed by both
      cell-mediated and humoral immune reactions. The number of anti-alpha 1
      antichymotrypsin (ACT) antibody-positive macrophages showed a proportional
      increase with the development of caries, and these cells may be involved in
      protecting against the tissue damage caused by proteases released from
      inflammatory cells, as well as having a defensive role by phagocytosis of toxic
      micro-organisms and damaged tissue residues. Thus anti-HLA-DR and anti-ACT
      antibody-positive cells might participate in both an efficient immune system and
      a tissue-protective mechanism in the human dental pulp.

PMID- 9015563
TI  - Characterization of sounds emanating from the human temporomandibular joints.
AB  - Sounds from the temporomandibular joint were recorded on audiotape from 238
      individuals by placing microphones in both ears. The recordings were later
      digitized at a sample rate of 1.7 kHz with 10-bit resolution and stored on
      computer disk. At least two open-close cycles were assessed from each individual;
      2707 different individual sounds were analysed in the time and frequency domains.
      The sounds were classified as: (a) single, short duration (clicks), (b) multiple,
      short-duration (creaks) and (c) long duration (crepitus). The sounds were further
      subclassified into either high or low amplitude by (i) the attack, which produced
      hard and soft categories and (ii) comparing the amplitude between sides-bilateral
      sounds were those with amplitudes differing by < 40 mV; the rest were unilateral.
      To establish the robustness of the classification 42 acoustic events were
      selected to be classified visually by three observers on two separate occasions.
      Intraobserver agreement was 82% (kappa = 0.75) while interobserver agreement was
      60% (kappa = 0.71). Statistically significant differences were noted between all
      classifications of sound. These were most marked in the time domain. A simple,
      automated classification scheme was devised that was capable of categorizing the
      sounds with 82% agreement (kappa = 0.71) compared to a human observer.

PMID- 9015564
TI  - Mesiodistal crown diameters of permanent teeth in Jordanians.
AB  - Mesiodistal crown diameters were measured from dental casts of the permanent
      teeth of 198 Jordanians (86 males and 112 females), aged 13.4-19.1 years. The
      differences in the crown diameters between the right- and left-hand sides of the
      dental arch were not significant, suggesting that either right- or left-side
      measurements could be taken to represent the tooth size of the study population.
      Males had significantly larger teeth than females, ranging from p < 0.05 for the
      incisors to p < 0.001 for the first molars. In both sexes, the maxillary lateral
      incisors showed the greatest variability [coefficient of variation (CV) 8.8%] and
      the first molar the least (CV 5.8%) in mesiodistal diameter. Canines displayed
      greater sexual dimorphism in crown size than any other tooth class. The
      cumulative tooth widths of males exceeded those of females by a sum of 3.1 mm in
      the maxilla and 3.6 mm in the mandible. These differences were statistically
      significant (p < 0.01). Comparisons of the mesiodistal crown diameters between
      population groups showed that Jordanians have tooth sizes close to those of
      Iraqis, but significantly larger than those of Yemenite-Jews, Caucasians and
      Chinese.

PMID- 9015565
TI  - Predominant cultivable microflora of supragingival dental plaque in Chinese
      individuals.
AB  - The aim of this study was to determine the predominant supragingival cultivable
      bacterial flora in Chinese individuals, using the experimental gingivitis model.
      A total of 11 healthy dental students, mean age 22.5 years (range 20-25) were
      recruited. All were provided with once-a-week dental prophylaxis and oral hygiene
      reinforcement for 3 weeks to ensure gingival health. In the fourth week, after
      prophylaxis, the participants entered a 14-day period without any plaque control.
      A plaque sample was collected at days 1, 3, 7 and 14 from the buccal surface of
      the upper right canine, second premolar, first premolar and first molar,
      respectively. Each sample was then dispensed in tryptic soy-broth transport
      medium and grown anaerobically to obtain pure cultures, which were subsequently
      identified. Results showed that Gram-positive cocci and rods were the predominant
      cultivatable species (51-61%) in the samples throughout the 14-day period; with
      time there was a decreasing percentage of cocci and an increasing percentage of
      rods. Gram-negative cocci and rods increased in proportion with the plaque age
      (11-37%). Streptococcus spp. were the predominant Gram-positive cocci while
      Actinomyces were the predominant Gram-positive rods isolated. Fusobacterium and
      Capnocytophaga spp. were the two most frequent Gram-negative anaerobic rods
      cultured. The results compared with those from other analogous studies from the
      West suggest the possibility of interracial differences in supragingival plaque
      flora.

PMID- 9015566
TI  - Measurement and comparison of the residual saliva on various oral mucosal and
      dentition surfaces in humans.
AB  - Using a paper-strip absorption method, the amounts of residual saliva on 20 soft
      tissue sites in different regions of the mouths of 20 individuals were surveyed
      once in the morning after a 12-h fast and again approx. 1-2 h after lunch. After
      swallowing, saliva at each site was immediately collected on filter-paper strips
      in a dipstick fashion for 5 s and the volumes were measured electronically with a
      Periotron micro-moisture meter. A clear pattern of wetness was evident and was
      almost identical for fasting and postprandial determinations. The hard palate and
      labial mucosa were covered with the least residual saliva; the floor of the mouth
      and back of the tongue were the wettest. In the same 20 participants, the amounts
      of residual saliva on various dentition sites were next measured and, as
      expected, much higher residual amounts were found in approximal embrasures and
      occlusal fossae than on adjacent facial or lingual smooth areas. Molars gave
      higher values than premolar and incisor embrasures. To relate residual saliva
      dipstick volumes to saliva thickness values, filter-paper strips were applied
      flat against the same mucosal or dentition surfaces in 10 of the participants,
      and the volume of the saliva absorbed was measured electronically as before. As
      the areas of the strips used were known, saliva thicknesses could be calculated.
      These ranged from 0.01 mm on the hard palate to 0.07 mm on the posterior of the
      dorsum of the tongue. For the incisor teeth, the calculated residual saliva
      thickness determined in the same way was about 0.01-0.02 mm. Blotting values
      plotted against dipstick values for oral sites where blotting could be readily
      performed showed a linear relation, which could be used as a standard curve to
      enable the easily done dipstick measurements in microlitres to be converted to
      saliva thicknesses in millimeters. As blotting could not be done in embrasures
      and occlusal fossae, this paper-strip absorption method was unsuitable for
      similar quantification of residual saliva in these sites but was done in another
      way described elsewhere. Overall, the results indicated that variations in dental
      morphology, and in the saliva secreted and available to the different oral
      regions, are the basic factors responsible for the wide variations in residual
      amounts of saliva seen on the diverse hard- and soft-tissue surfaces of human
      mouths. Also, finding that the hard palate and inner lips are covered by very
      thin films of residual saliva suggested that only a small reduction in their
      quantity would be needed to trigger the dry mouth sensation in hyposalivators.

PMID- 9015567
TI  - Hyaluronan (hyaluronic acid) in human saliva.
AB  - Hyaluronan (hyaluronic acid) is a glycosaminoglycan that functions as a
      constituent of ground substance, a mediator of cell proliferation and would
      healing, and that plays a prominent part in tumorigenesis as well as in
      embryogenesis. Its presence and possible role in saliva has been subjected to
      little study. Unstimulated and stimulated pure parotid and mixed saliva was
      obtained from 10 volunteers. The protein content of the samples was assayed and
      the hyaluronan concentration was evaluated by means of an enzyme immunosorbent
      like assay using a hyaluronan-binding peptide. Stimulated whole saliva had the
      highest protein content (mean 1.26 mg/ml) followed by unstimulated parotid saliva
      (1.15 mg/ml), stimulated parotid saliva (0.95 mg/ml) and unstimulated whole
      saliva (0.93 mg/ml). Absolute hyaluronan concentrations were highest in
      unstimulated whole saliva (mean 459.2 ng (nanograms)/ml), and lowest in
      stimulated parotid saliva (82.7 ng/ml). When hyaluronan concentrations are
      expressed as ng/mg of protein, the highest are in the unstimulated whole saliva
      (mean 477.5 ng/mg protein) followed by stimulated parotid saliva (229.7 ng/mg),
      unstimulated parotid saliva (179.6 ng/mg) and stimulated whole saliva (159.9
      ng/mg). There are wide variations in the levels of hyaluronan in human saliva
      depending on the type of saliva and the conditions at the time of collection.
      Regulation of hyaluronan metabolism represents an intricate balance between
      production and degradation, and it is unclear whether elevated concentrations of
      hyaluronan in response to tissue proliferation, regeneration or repair. The
      hyaluronan may contribute to the healing properties of saliva, assisting in
      protecting the oral mucosa and adding to the lubricating properties of saliva.

PMID- 9015568
TI  - Effects of short-term (2 weeks) streptozotocin-induced diabetes on acetylcholine
      and noradrenaline in the salivary glands and secretory responses to cholinergic
      and adrenergic sialogogues in mice.
AB  - Acetylcholine and noradrenaline concentrations in the submandibular, parotid and
      sublingual glands, and pilocarpine-, isoproterenol- and phenylephrine-induced
      salivation, were estimated in streptozotocin (STZ)-induced diabetic mice.
      Diabetic mice showed significant increases in acetylcholine and noradrenaline
      (expressed as nmol/gland) in sublingual and submandibular glands, respectively.
      The total volume of crude whole saliva in diabetic mice in response to
      pilocarpine and isoproterenol but not to phenylephrine was significantly reduced.
      These results suggest that alterations in the neurotransmitter levels and
      secretory function in the salivary glands occur rapidly after the induction of
      STZ diabetes, and that the secretory function appears to be more susceptible to
      effects of diabetes in the early stages than the autonomic nervous system. Since
      the alterations in neurotransmitter concentrations in diabetic salivary glands
      were slight and partial, it seems that they are unrelated to the markedly reduced
      salivation in response to pilocarpine and isoproterenol observed in these short
      term diabetic mice.

PMID- 9015569
TI  - A mathematical model of potassium ion diffusion in dentinal tubules.
AB  - Desensitizing agents containing potassium ions (K+) are believed to inactivate
      intradental nerves by raising extracellular [K+]. A mathematical model was used
      to investigate factors affecting [K+] in dentinal tubules. The most important
      factors affecting the steady-state tubular [K+] were the tubular fluid-flow
      velocity, salivary [K+] and the permeability to potassium (k) of the barrier
      between the tubule and the pulp. Tubular [K+] decreased with increasing outward
      flow velocity and increasing k. whereas the dimensions of the tubule and
      odontoblast process had little effect. Following a 1 min simulated application of
      500 mmol/1 K+ to the dentine surface, [K+] at the inner end of the tubule
      increased above steady-state levels for 20-30 min. The maximum [K+] attained at
      the inner end of the tubule was around 30 mmol/l for an impermeable barrier (k =
      0) and flow velocity of 1.4 microns/s, but lower maximum tubular [K+] were
      achieved when either the outward flow velocity or k was increased. The model
      suggests that applying potassium-containing preparations to dentine may increase
      [K+] at the inner ends of dentinal tubules to levels sufficient to inactivate
      intradental nerves. However, the localized increase in [K+] is transient, and the
      concentration change will be lessened by conditions that increase the tubular
      fluid-flow velocity or the permeability of the barrier between the tubule and
      pulp.

PMID- 9015570
TI  - Elevation of intracellular cAMP by noradrenaline and vasoactive intestinal
      peptide in striated ducts isolated from the rabbit mandibular salivary gland.
AB  - Salivary gland intralobular ducts are responsible for the modification of the
      electrolyte composition of the primary fluid secreted by the acini. However, the
      intracellular messengers that regulate this and other intralobular duct cell
      processes have not been fully characterized. To investigate the possibility that
      cAMP-mobilizing agonists may be involved, intralobular (striated) ducts were
      isolated from the rabbit mandibular salivary gland by tissue dissociation and
      microdissection and maintained in tissue culture overnight. Individual duct
      fragments were stimulated with the secretory agonists noradrenaline, vasoactive
      intestinal peptide (VIP) and substance P and their cAMP content measured by
      acetylated radioimmunoassay. Both noradrenaline and VIP elevated intracellular
      cAMP content concentration dependently, but substance P did not. The response to
      noradrenaline was blocked by the beta-adrenoceptor antagonist propranolol, but
      not by the alpha-adrenoceptor antagonist prazosin. Application of the VIP
      analogue [D-p-Cl-Phe6, Leu17]-VIP decreased the VIP-induced cAMP response. These
      results demonstrate that striated intralobular duct cells possess beta
      adrenoceptors and peptidergic receptors that are coupled to adenylate cyclase and
      activated by noradrenaline and VIP, respectively. By elevating ductal cAMP
      content, these agonists may regulate both the electrolyte content of the primary
      saliva and the secretion of protein(s) from the ducts.

PMID- 9015571
TI  - Biochemical comparison of plaque fluid on tooth and acrylic surfaces during a
      sucrose challenge.
AB  - Previous studies have investigated variations in dental plaque fluid composition
      within a single mouth after a sucrose exposure. The purpose of this study was to
      determine a potential source of calcium and phosphorus in plaque by comparing the
      pH, calcium and phosphorus concentrations in plaque fluid obtained from an
      acrylic appliance with samples taken from supragingival tooth surfaces within the
      same individual after a sucrose challenge. Separate plaque samples from 14
      individuals were collected from an acrylic appliance or tooth surfaces within
      same individual before and 15 min after a 20% sucrose rinse. Each plaque sample
      was centrifuged and nanolitre samples of plaque fluid were analysed for pH with a
      pH microelectrode, for total calcium concentration by atomic absorption in a
      graphite furnace, and for phosphorus concentration by spectrophotometry. There
      was an increase in the calcium and phosphorus concentration in the plaque after
      the sucrose challenge and a significant increase in calcium and phosphorus
      concentrations in the plaque taken from the teeth compared to the acrylic
      surfaces. The results indicate that the increased total calcium and phosphorus in
      plaque during a sucrose challenge is probably derived from the demineralization
      of enamel or extracellular demineralized components.

PMID- 9015572
TI  - The effect of a nitric oxide donor and an inhibitor of nitric oxide synthase on
      blood flow and vascular resistance in feline submandibular, parotid and
      pancreatic glands.
AB  - The aim was to examine whether (1) blood flow and vascular resistance are altered
      in response to exogenous nitric oxide and (2) whether endogenous synthesis of
      nitric oxide participates in the haemodynamic regulation of the submandibular,
      parotid and pancreatic glands. Experiments were performed on anaesthetized,
      artificially ventilated cats. Mean arterial blood pressure, heart rate, blood
      gases, cardiac output and tissue blood flow were determined before and 15 min
      after intravenous administration of either the nitric oxide donor SIN-1 (3
      morpholinosydnonimine, 1 mg/kg, n = 10) or the competitive nitric oxide synthase
      inhibitor NOLA (NG-nitro-L-arginine, 30 mg/kg, n = 9) blood flow was measured by
      a radioactive-labelled microsphere method. In the SIN-1 group, in spite of a
      serious decrease in mean arterial blood pressure (p < 0.001), the blood flow in
      the glands remained unchanged. The vascular resistance decreased after SIN-1 in
      the submandibular and pancreatic glands (p < 0.001 and p < 0.05, respectively),
      and was slightly reduced in the parotid. The NOLA increased mean arterial blood
      pressure (p < 0.01) and reduced the blood flow in the submandibular and
      pancreatic glands (p < 0.01 and p < 0.001, respectively), but the decrease in the
      parotid was not significant. Vascular resistance increased after NOLA in all
      three glands (p < 0.05, p < 0.001 and p < 0.05). These findings suggest that
      basal nitric oxide production in these exocrine glands is sufficient to modulate
      vascular resistance. Moreover, the release of endogenous NO from the nerves
      and/or endothelium is probably involved in the regulation of vascular tone. The
      nitric oxide-dependent component of blood-flow regulation, however, seems to be
      less pronounced in the parotid gland.

PMID- 9015573
TI  - Effects of adjuvant on neuropeptide-like immunoreactivity in experimentally
      induced temporomandibular arthritis in rats.
AB  - Substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)-
      and neuropeptide Y (NPY)-like immunoreactivities (-LI) were examined in
      cerebrospinal fluid (CSF), plasma and temporomandibular joint (TMJ) perfusates in
      rats 1 and 12 h after inoculation at the base of the tail (0.05 ml) or injection
      into the right TMJ (0.01 ml) of heat-killed Mycobacterium butyricum in paraffin
      oil. In the rats inoculated at the base of the tail (polyarthritic rats), there
      was a significant increase of CGRP-LI and NKA-LI. The changes in neuropeptide-LI
      were not as marked in the CSF of rats injected with adjuvant in one TMJ
      (monoarthritic rats) as in the polyarthritic group. Instead, the most significant
      changes in the monoarthritic rats were seen in the perfusates of both TMJs. The
      increases in SP-, NKA-, CGRP- and NPY-LI were significant for both TMJs and more
      pronounced than in the polyarthritic rats. The results show that inoculation of
      adjuvant at the base of the tail induces significant changes of neuropeptide-LI
      predominantly in CSF, whilst an intra-articular injection induces bilateral
      changes in neuropeptide-LI in joint perfusate. Therefore, two different neural
      mechanisms may be involved early in adjuvant-induced poly- and monoarthritis.

PMID- 9015574
TI  - A 2 week pair-fed study of early X-irradiation effects on rat major salivary
      gland function.
AB  - Salivary gland function is affected shortly after irradiation of the head and
      neck. An intense oral mucositis develops after exposure and may interfere with
      ingestion. The effects of restricted food and water intake on the secretory
      output of rat major salivary glands were examined. Parotid and submandibular
      salivary output and body weight were measured in rats at 4, 8, 11 and 14 days
      after 15 Gy X-irradiation of the head and neck. Comparisons were made with two
      groups: a non-irradiated group with food and water intake restricted to that of
      the irradiated group (pair-fed), and a non-irradiated, ad libitum-fed control
      group. Parotid saliva output was significantly decreased in the irradiated group
      at 4, 8, and 11 days compared with the control group. The pair-fed rats also had
      significantly decreased parotid output at these time points and their parotid
      function did not differ from that of the irradiated animals. At 14 days, all
      three groups demonstrated similar parotid function. Submandibular salivary output
      was not affected to the same extent. Only at a single time point (11 days) was
      flow significantly decreased in the irradiated group. Total body weight was less
      than that of control rats for both the irradiated and pair-fed animals at all
      time points. These results suggest that the early effects of radiation on
      salivary glands are due, in part, to limited intake of food and water during the
      immediate post-irradiation period.

PMID- 9015576
TI  - Are transvestites necessarily heterosexual?
AB  - A survey of 372 male cross-dressers gathered data about present and childhood
      experiences and attitudes in light of the growing knowledge about transvestism.
      This article focuses on data related to sexual orientation, particularly in
      relationship to the definition of transvestism in the Diagnostic and Statistical
      Manual of Mental Disorders of the American Psychiatric Association. It is argued
      that transvestism is not necessarily a heterosexual phenomenon.

PMID- 9015575
TI  - Epidermal growth factor in gingival crevicular fluid and its binding capacity in
      inflamed and non-inflamed human gingiva.
AB  - Epidermal growth factor (EGF) is a pro-inflammatory small peptide (6000 Da) with
      a variety of biological activities including stimulation of cell differentiation
      and mediation of proteolysis by binding to its specific receptor on the cell
      surface. The purpose of this study was to determine the levels of EGF in gingival
      crevicular fluid (GCF) and the EGF-binding capacity to its receptor in gingival
      tissue. The GCF samples were collected from six patients by inserting paper
      strips into shallow (< 5 mm) and deep pockets (> or = 5 mm) for 30 s. The strips
      were soaked in 0.2 M acetate for extraction and the EGF in the supernatants was
      analysed by radioimmunoassay. To determine the binding capacity of EGF to its
      receptor, inflamed gingival tissues (pocket depth > or = 5 mm, Gingival Index =
      1, 2 or 3) were collected during periodontal flap surgery and non-inflamed
      gingival tissues (pocket depth < 5 mm, Gingival Index = 0) were collected during
      surgical "crown lengthening' for aesthetic purposes. The tissues were pooled by
      group, homogenized for membrane preparation and the supernatants obtained after
      centrifugation were used in a 125IEGF binding assay. To determine the effect of
      inflammation on gingival EGF receptor, inflamed and non-inflamed gingival tissues
      were collected from six patients and prepared similarly to the binding assay.
      Gingival preparations were then electrophoresed for Western blot analysis with
      EGF receptor antiserum. The EGF level in GCF was significantly lower (P < 0.05)
      in the samples collected from pockets > or = 5 mm (0.9 +/- 0.6 ng/ml) than in
      those from pockets < 5 mm (2.4 +/- 2.1 ng/ml). The average Gingival Index was
      higher (2.6 +/- 0.6) in pockets > or = 5 mm than in pockets < 5 mm (1.4 +/- 1.0).
      Specific binding of 125I-EGF to its receptor in inflamed gingiva was 2.7-fold
      higher than in non-inflamed gingiva (14.4 +/- 4.9 vs 5.4 +/- 1.8 fmol/g wet
      tissue). Western blot analysis showed two major immunoreactive bands (180 and 120
      kDa), which represent EGF receptor and its degradation products, in inflamed
      gingiva. The findings show that inflammation activates EGF binding capacity in
      gingiva and that the up-regulation of EGF receptor in inflamed gingiva might be
      associated with a lowered concentration of EGF in GCF produced adjacent to
      inflamed gingiva. This up-regulation of EGF receptor during inflammation might be
      an important mechanism in the pathogenesis of periodontal disease.

PMID- 9015577
TI  - Comorbidity of gender dysphoria and other major psychiatric diagnoses.
AB  - Previous studies suggest that many transsexuals evidence an Axis I diagnosis
      according to the DSM-IV classification (e.g., psychoses, major affective
      disorder). The current study examined retrospectively the comorbidity between
      gender dysphoria and major psychopathology, evaluating the charts of 435 gender
      dysphoric individuals (318 male and 117 female). All had undergone an extensive
      evaluation, addressing such areas as hormonal/surgical treatment, and histories
      of substance abuse, mental illness, genital mutilation, and suicide attempts. In
      addition, a subgroup of 137 individuals completed the MMPI. Findings revealed
      over two thirds were undergoing hormone reassignment, suggesting a commitment to
      the real-life cross-gender process. One quarter had had problems with substance
      abuse prior to entering treatment, but less than 10% evidenced problems
      associated with mental illness, genital mutilation, or suicide attempts. Those
      completing the MMPI (93 female and 44 male) demonstrated profiles that were
      notably free of psychopathology (e.g., Axis I or Axis II criteria). The one scale
      where significant differences were observed was the Mf scale, and this held true
      only for the male-to-female group. Psychological profiles as measured by the MMPI
      were more "normal" in the desired sex than the anatomic sex. Results support the
      view that transsexualism is usually an isolated diagnosis and not part of any
      general psychopathological disorder.

PMID- 9015578
TI  - The relationships among ejaculatory control, ejaculatory latency, and attempts to
      prolong heterosexual intercourse.
AB  - Although premature ejaculation (RE) is considered the most common male sexual
      dysfunction, progress in understanding it has been hampered by the lack of a
      commonly accepted definition. Several different criteria have been used to assess
      RE with no attempt to validate the extent to which they are related. The current
      study assessed, in a sample of university men, the occurrence and relationships
      among four commonly applied RE criteria: perceived control over the occurrence of
      ejaculation, latency from vaginal penetration to ejaculation, satisfaction with
      perceived degree of ejaculatory control, and concern over the occurrence of rapid
      ejaculation. Other aspects of ejaculatory behavior were also assessed such as the
      thoughts and techniques men used to prolong intercourse and delay ejaculation.
      Results indicated that although the four RE criteria were significantly
      correlated, the magnitudes of these correlations were small. This suggests that
      these commonly used RE criteria are largely independent and are not
      interchangeable and that research in this area needs to adopt a multivariate
      approach to assessment. Men's erotophilia/erotophobia was not related to RE.
      While use of several ejaculatory delaying techniques were individually and
      jointly predictive of ejaculatory control and/or ejaculatory evidence, there was
      no strong support for any specific pattern of behavior that is related to better
      control and longer latencies. Further, experts were not able to distinguish the
      ejaculatory delaying techniques of the men with the poorest control and shortest
      latencies from those of the men with the best control and longest latencies.

PMID- 9015579
TI  - Yohimbine, erectile capacity, and sexual response in men.
AB  - In a double-blind, placebo-controlled crossover study on a group of men with
      erectile problems and a sexually functional comparison group, the effect of
      yohimbine (up to 30 mg/day) was assessed on a number of objective and subjective
      measures of erectile response through the use of daily logs and
      psychophysiological laboratory procedures involving response to visual sexual
      stimulation (VSS). Sexual desire, arousal, and ejaculatory response were also
      assessed. Results indicated no effect of yohimbine on most aspects of sexual
      response in sexually functional men. Mixed effects were found on measures of
      sexual function in men erectile dysfunction, with 3 of 11 men reporting strong
      positive effects. Under yohimbine, frequency of sexual activities increased, as
      did self-assessed genital response to VSS. Daily diaries indicated increased
      sexual arousal and erectile response during masturbation but not intercourse. A
      number of other measures, including NPT and retrospective summaries of erectile
      functioning at the end of drug phases, showed no effect. Results are discussed in
      terms of possible yohimbic effects on psychological factors that modulate overall
      sexual response, and consequently, erectile response.

PMID- 9015580
TI  - Classical conditioning of female sexual arousal.
AB  - The classical conditioning of subjective and physiological aspects of female
      sexual arousal was examined. Experimental subjects were run in a delayed
      conditioning design, where an amber light was paired with excerpts from erotic
      videos. Control subjects received presentations of the same amber light and
      videos, but these presentations did not overlap with one another. Dependent
      variables included subjective ratings of arousal to the light and the videos as
      well as change in vaginal pulse amplitude assessed during exposure to the
      different stimuli. Experimental subjects evidenced increased arousal to the light
      over conditioning trials, as assessed by subjective ratings of sexual arousal.
      This finding is suggestive of a learned effect. However, results failed to
      indicate significant differences between experimental control groups. Therefore,
      the increased arousal to the light evidenced by experimental subjects may not be
      due to classical conditioning. Suggestions regarding these findings, clinical
      implications, and future research are discussed.

PMID- 9015581
TI  - Assessment of sexual functioning for Chinese college students.
AB  - Participating in this study were 305 Chinese college students in Hong Kong.
      Objectives included (i) examination of the psychometric properties of the Chinese
      version of the Derogatis Sexual Functioning Inventory (DSFI), (ii) exploration of
      the associations among various domains of sexual functioning, and (iii)
      description of Chinese students' sexual behavior. The Chinese DSFI shows
      satisfactory internal consistency, except the Information, Drive, and
      Satisfaction subscales. In general, sex-related domains such as sexual
      information, experience, drive, attitudes, fantasy, and satisfaction were related
      to each other and to body image. Compared to their counterparts in the U.S.,
      Chinese college students were relatively sexually inexperienced and conservative.
      Mean ages of students having their first sexual intercourse experience were 17.14
      for males and 18.13 for females; 11% of the students had premarital sexual
      intercourse experience, and the mean frequencies were once weekly for males and
      once or twice per month for females. Compared to female students, twice as many
      males acknowledged masturbation (21.4 vs. 43.8%), 4.2-8.2% students had
      experienced oral-genital sexual stimulation and 0-1.2% anal sexual activities.

PMID- 9015582
TI  - Child abuse in sport.

PMID- 9015583
TI  - Creatine supplementation: recent developments.

PMID- 9015584
TI  - Gender verification: a concept whose time has come and passed?

PMID- 9015585
TI  - Sports for the disabled: the evolution from rehabilitation to competitive sport.

PMID- 9015586
TI  - A national strategy for the promotion of physical activity.

PMID- 9015587
TI  - Advances in the understanding of throwing injuries of the shoulder.

PMID- 9015588
TI  - Head injuries in sport.
AB  - Injuries to the head and neck are the most frequent catastrophic sports injury,
      and head injuries are the most common direct athletic cause of death. Although
      direct compressive forces may injure the brain, neural tissue is particularly
      susceptible to injury from shearing stresses, which are most likely to occur when
      rotational forces are applied to the head. The most common athletic head injury
      is concussion, which may very widely in severity. Intracranial haemorrhage is the
      leading cause of head injury death in sports, making rapid initial assessment and
      appropriate follow up mandatory after a head injury. Diffuse cerebral swelling is
      another serious condition that may be found in the child or adolescent athlete,
      and the second impact syndrome is a major concern in adult athletes. Many head
      injuries in athletes are the result of improper playing techniques and can be
      reduced by teaching proper skills and enforcing safety promoting rules. Improved
      conditioning (particularly of the neck), protective headgear, and careful medical
      supervision of athletes will also minimise this type of injury.

PMID- 9015589
TI  - Subcutaneous and visceral fat distribution and daily physical activity:
      comparison between young and middle aged women.
AB  - OBJECTIVE: To examine the effects of aging and physical activity on distribution
      patterns in subcutaneous and visceral fat. METHODS: Distributions of subcutaneous
      rat mass at six segments (face and neck, forearm, upper arm, trunk, thigh, and
      lower leg) were determined by adipose tissue thickness measurements by B mode
      ultrasonogram and body surface areas. Visceral fat mass was calculated by
      subtracting subcutaneous fat mass from the total fat mass determined
      hydrodensitometrically. Measurements were made on young and middle aged, trained
      and sedentary women (four groups). RESULTS: Per cent body fat was lower in
      trained than in sedentary individuals, both in the young and the middle aged
      subjects. The distribution of subcutaneous fat mass differed between sedentary
      and trained women. Trained young women had a reduced subcutaneous fat mass
      compared to sedentary young subjects in all segments except face and neck; the
      disparity between middle aged sedentary and trained women was limited to upper
      arm and trunk (P < 0.01 each), with no significant difference in face and neck,
      forearm, and lower limb segments. Differences in visceral fat mass between
      sedentary and trained subjects were similar for young and middle aged women
      (young, 2.5 v 3.7 kg; middle aged, 4.0 v 6.5 kg). CONCLUSIONS: Women who exercise
      regularly appear to accumulate less adipose tissue, especially in upper arm and
      trunk segments as they get older, with visceral fat mass remaining lower than in
      sedentary individuals.

PMID- 9015590
TI  - Seasonal variations in the body composition of lightweight rowers.
AB  - OBJECTIVE: To monitor the seasonal body composition alterations in 18 lightweight
      rowers (six females, 12 males) across a rowing season incorporating preseason,
      early competition, competition, and postseason. METHODS: Subject age was 23.1 (SD
      4.5) years, height 170.8 (5.6) cm (female, 23.5 (3.5) years, 180.5 (2.7) cm
      (male). Body weight, fat mass, and fat-free mass (FFM) were assessed using dual
      energy x ray absorptiometry (DXA-L Lunar) and skinfold techniques. Weight control
      techniques were documented before major regattas by a questionnaire. RESULTS:
      Female body weight was reduced from 61.3 (2.9) to 57.0 (1.1) kg (5.9%), while
      male body weight was reduced from 75.6 (3.1) to 69.8 (1.6) kg (7.8%) preseason to
      competition season respectively. These body weight reductions were mirrored by a
      significant reduction in fat mass as indicated by the sum of skinfolds [female
      seven sites: 80.9 (8.1) to 68.2 (11.8) mm; male eight sites: 54.2 (8.7) to 41.8
      (4.8) mm], percentage body fat [female 22.1 (1.0) to 19.7 (2.4)%; male 10.0 (0.9)
      to 7.8 (0.8)%], and total fat [female 12.5 (5.2) to 10.9 (1.4) kg; male 7.3 (1.9)
      to 5.6 (1.8) kg] (DXA). In contrast, no changes were observed in FFM despite a
      season of intensive rowing training. Seasonal body weight control was achieved
      through reduced total energy and dietary fat intakes. Acute body weight
      reductions were achieved by exercise in 73.3% of participants, food restriction
      in 71.4%, and fluid restrictions in 62.9%. CONCLUSIONS: Seasonal body weight
      alterations in lightweight rowers are in response to a significant reduction in
      fat mass. However, the weight restrictions appear to be limiting an increase in
      FFM which could be beneficial to rowing performance.

PMID- 9015591
TI  - A new approach to the assessment of anaerobic metabolism: measurement of lactate
      in saliva.
AB  - OBJECTIVE: To test the hypothesis that saliva lactate concentrations may reflect
      those present in blood and that saliva lactate can be used as a very convenient
      and useful variable in the study of anaerobic metabolism. METHODS: Parallel
      determinations were made of lactate in saliva and in capillary blood samples,
      obtained at 3 min intervals from nine individuals during the performance of a
      maximum graded exercise test on a cycle ergometer against increasing workloads
      (from 25 up to a maximum of 300 W). Lactate determinations were done by means of
      an electroenzymatic method using 25 microliters samples in both types of fluids.
      RESULTS: For each situation, the concentration of lactate in saliva was shown to
      be about 15% of that in plasma but it followed the same pattern of evolution
      during the exercise test. A good correlation (r = 0.81) between blood and saliva
      lactate concentrations was found. The precision of the method was very good, with
      a coefficient of variation ranging (n = 10) between 2.2% for samples with very
      low lactate concentrations and 0.7% for sample with moderate lactate
      concentrations. Lactate appeared to be very stable in saliva over a period of 40
      days after collection, when kept at 4 degrees C. The values obtained after this
      period were virtually identical to those shown in fresh samples. CONCLUSIONS:
      Determination of lactate in saliva can be used as an alternative to determination
      in blood, overcoming most of the drawbacks of the procedures being used at
      present, since the collection of the samples required no special expertise.

PMID- 9015592
TI  - Gender verification in sports by PCR amplification of SRY and DYZ1 Y chromosome
      specific sequences: presence of DYZ1 repeat in female athletes.
AB  - OBJECTIVE: To perform genetic sex typing during the Barcelona Olympic Games using
      polymerase chain reaction (PCR) amplification of Y chromosome specific sequences.
      METHODS: The assay consisted of the amplification of a specific sequence
      corresponding to the repeat DYZ1 element from buccal smears samples of 2406
      female competitors. Positive samples were reanalysed for the presence of another
      Y chromosome specific gene, SRY. RESULTS: The expression of these two elements
      did not always correlate; six samples were found where the presence of DYZ1 but
      not SRY was detected. This presence of DYZ1 sequence in female athletes is higher
      than in unselected females, where no DYZ1 amplification was observed in any of
      the 1629 samples analysed. CONCLUSIONS: Amplification of DYZ1 repeat should not
      be used as the only index for determining genetic sex, at least in sporting
      events.

PMID- 9015593
TI  - Effect of passive stretching and jogging on the series elastic muscle stiffness
      and range of motion of the ankle joint.
AB  - OBJECTIVE: To determine the effect of stretching and jogging on the series
      elastic muscle stiffness of the plantar flexors and on the range of dorsiflexion
      at the ankle joint. METHODS: 24 healthy subjects participated in this study. Each
      subject undertook all of the following protocols, in random order: (1) stretching
      protocol: five 30 s static stretches with 30 s rest between stretches; (2)
      aerobic jogging protocol: subjects ran on a treadmill for 10 min at 60% of their
      maximum age predicted heart rate; (3) combined protocol: subjects ran first and
      then stretched. A damped oscillation technique was used to measure the series
      elastic stiffness of the plantar flexors. Dorsiflexion of the ankle was assessed
      with a weights and pulley system that moved the ankle joint from a neutral
      position into dorsiflexion passively. Electromyography was used to monitor the
      activity of the plantar and dorsiflexors during these procedures. The statistical
      analysis of these data involved an analysis of covariance. RESULTS: For
      decreasing series elastic muscle stiffness running was more effective than
      stretching (P < 0.05). In contrast, the results for range of motion showed that
      the combination protocol and the stretching only protocol were more effective
      than the running only protocol (P < 0.05) for increasing dorsiflexion range of
      motion at the ankle. CONCLUSIONS: Both jogging and static stretching exercises
      appear to be beneficial to individuals participating in sporting activities.

PMID- 9015594
TI  - Musculoskeletal injuries in the ultramarathon: the 1990 Westfield Sydney to
      Melbourne run.
AB  - OBJECTIVE: To document the injuries sustained by participants in a 1005 km
      ultramarathon. METHODS: Clinical notes were reviewed on entrants in the 1005 km
      Sydney to Melbourne ultramarathon. An injury was recorded following self referral
      by a participant or if the history obtained from the runner or his support crew
      indicated the likelihood of a significant injury which could have an impact upon
      performance. RESULTS: 64 injuries were found in 32 runners. The knee (31.3%) and
      ankle (28.1%) regions were most commonly injured. The most common single
      diagnosis was retropatellar pain syndrome, and Achilles tendinitis and medial
      tibial stress syndrome were the next most common injuries.
      Peritendinitis/tendinitis of the tendons passing under the extensor retinaculum
      at the ankle, an injury infrequently reported in other sports, was common (19% of
      all injuries). CONCLUSIONS: The injuries were typically associated with running
      but 12 (19% of the total) involved the tendons of the muscles of the anterior
      compartment of the lower leg, and in almost every case the major site of
      inflammation was at the extensor retinaculum at the anterior aspect of the ankle.
      This injury appears to be relatively specific to the ultramarathon
      "ultramarathoner's ankle".

PMID- 9015595
TI  - Incidence of injuries and other health problems in the Auckland Citibank
      marathon, 1993.
AB  - OBJECTIVE: To describe the incidence of injuries and other health problems
      sustained during participation in a marathon. METHODS: A cohort study was
      undertaken involving the 1993 Auckland Citibank marathon participants.
      Demographic data and information on injuries and other health problems sustained
      during, immediately after, and 7 d following the marathon were obtained from a
      pre-race questionnaire, the medical aid posts, and a post-race questionnaire.
      RESULTS: Of the 1219 starters, 916 (75.1%) completed both questionnaires. Seventy
      five individuals (6.2%) sought assistance at the medical aid posts. During or
      immediately after the marathon, 283 systemic health problems were reported by 218
      respondents (23.8%) and 2671 specific health problems were reported by 846
      respondents (92.4%). In the 7 d following the marathon, 1905 specific health
      problems were reported by 723 respondents (79.2%). The majority of the specific
      health problems were blisters, stiffness, and pain, predominantly involving the
      lower limbs. CONCLUSIONS: Although a high proportion of participants experienced
      health problem during the race, very few of these problems were serious. Many of
      the entrants were still experiencing problems 7 d after the marathon.

PMID- 9015596
TI  - Trampoline injury in New Zealand: emergency care.
AB  - OBJECTIVE: To examine trampoline related injuries resulting in emergency
      department attendance. METHODS: Cases were identified by searching free text
      descriptions of the circumstances of injury contained in the records of the
      emergency department of a large city hospital. RESULTS: 114 cases were identified
      for a 12 month period, giving an incidence rate of 108 per 100,000 population per
      year (95% confidence interval = 89 to 129) compared with 9.3 hospital admissions
      per 100,000 population per year (95% confidence interval = 8.3 to 10.4) for a
      corresponding period reported in earlier research from New Zealand. This
      suggested that for every one hospital admission there are approximately 12
      emergency department attendances. Of the cases, 95% were aged less than 20 years.
      As for the earlier research, falls from the trampoline to the surrounding surface
      were the commonest cause of injury. In the present study, sprains and strains
      were the commonest type of injury (40%), and the body site most frequently
      involved was the lower limb (46%). CONCLUSIONS: The findings support the
      conclusion from earlier research that although existing trampoline standards
      address many of the issues relating to trampoline safety, the need remains for
      measures to reduce the impact of falls from the trampoline to the ground surface
      and to prohibit the use of trampolines as unsupervised "play equipment".

PMID- 9015597
TI  - Injury in rugby league: a four year prospective survey.
AB  - OBJECTIVE: To investigate the incidence of injury in English professional rugby
      league over a period of four playing seasons. METHODS: All injuries that were
      received by players during match play were recorded. Each injury was classified
      according to site, type, player position, team playing for, activity at the time
      of injury, and time off as a result of injury. RESULTS: The overall injury rate
      was 114 (95% confidence interval 105 to 124) per 1000 playing hours, the most
      frequent type of injury were muscular injuries [34 (29 to 40) per 1000 playing
      hours], while the most frequently injured site was the head and neck region [38
      (16 to 25) per 1000 playing hours]. Players received the largest percentage of
      injuries when being tackled [46.3% (41.9 to 50.7)], most injuries required less
      than one week away from playing and training [70.1% (66.1 to 74.2)], and forwards
      had a higher injury rate than backs (139 v 93 injuries per 1000 hours).
      CONCLUSIONS: The high rates of injury in rugby league are undoubtedly due to the
      high amount of bodily contact in the game. Being tackled has the highest risk of
      injury, because of being hit forcibly by other players. Forwards suffer higher
      injury rates than backs, probably because they are involved in a larger number of
      physical collisions.

PMID- 9015598
TI  - Sport and delinquency: an examination of the deterrence hypothesis in a
      longitudinal study.
AB  - OBJECTIVE: To determine whether involvement in sporting activity in mid
      adolescence would deter delinquent behaviour in late adolescence. METHODS:
      Members of a longitudinal cohort study were interviewed at ages 15 and 18 years
      and, among other topics, were asked questions relating to involvement in physical
      activity and delinquent behaviour. Logistic regression models were used to
      examine the relation between sports involvement and delinquency at age 15 years
      and delinquency at age 18. RESULTS: After controlling for delinquent behaviour
      and psychosocial factors at age 15, females with moderate or high levels of
      sporting activity, and males with high levels of sporting activity, were
      significantly more likely to be delinquent at age 18 years than those with low
      levels of sporting activity. No significant association was found between
      sporting activity and aggressive behaviour, team sport participation and
      delinquency, and team sport participation and aggressive behaviour. CONCLUSIONS:
      This study did not support the deterrence hypothesis and showed that high
      involvement in sporting activity, but not team sport, was associated with a
      subsequent increase in delinquent behaviour.

PMID- 9015599
TI  - The effect of meditation on shooting performance.
AB  - OBJECTIVE: To study effects of meditation on the shooting performance. METHODS:
      25 elite shooters were investigated in an independent groups design. The results
      in standardised test shootings indoors and in ordinary competitions outdoors were
      assessed before and after regular meditation training for the experimental group.
      The experience of tension during the test shootings was self recorded on a visual
      analogue scale (VAS). RESULTS: The competition results in the outdoor season
      (1993), just after the meditation training period, compared with the results the
      previous season (1992), were better in the meditation group (P < 0.05). No
      significant difference between the groups was observed in the test shootings
      before and after the relaxation intervention. A significant association was shown
      between low tension and the results in the test shootings (correlation r = 0.42,
      P < 0.0001; Wilcoxon rank sum test, z = -3.36, P < 0.001); 18% (= r2) of the
      variance in performance was explained by tension. CONCLUSIONS: Meditation may
      enhance competitive shooting performance.

PMID- 9015600
TI  - Outbreak of Salmonella food poisoning at Junior World Rowing Championships.
AB  - This paper describes an outbreak of Salmonella enteriditis occurring at the
      Junior World Rowing Championships at Poznan, Poland, in August 1995 which was to
      have a significant effect on the performance of several of the largest national
      teams.

PMID- 9015601
TI  - Evaluation of elite British cyclists: the role of the squad medical.
AB  - OBJECTIVE: To describe and report results from the procedures and protocols used
      by the British Cycling Federation during the squad medicals of its elite
      cyclists. METHODS: Screening of over 500 elite riders has been done by doctors,
      dentists, physiotherapists, opticians, and dietitians since 1990. A questionnaire
      provided additional information on musculoskeletal problems. RESULTS: 523 riders
      have been examined and 92 (17.5%) have been referred for further assessment or
      treatment. Most of these riders were sent either to their own general
      practitioner or to the British Olympic Medical Centre. The questionnaire was
      completed by 81% of riders. Low back pain was the most common problem that riders
      encountered (60%), and knee pain the second most common (33%). Four riders failed
      the eye examination, and a further 11 were classed as borderline. Twenty one per
      cent of riders undergoing dental examination needed further dental treatment.
      CONCLUSIONS: The squad medical is an important and useful strategy for evaluating
      elite British cyclists. It shows that a structured system can help early
      diagnosis and treatment to provide injury-free cyclists at the start of a
      competitive season. The results from the questionnaire confirm previously
      unsubstantiated opinions about the incidence of musculoskeletal injuries in
      cyclists.

PMID- 9015602
TI  - A review of the British Journal of Sports Medicine 1991-5.
AB  - OBJECTIVE: To review 5 years of the British Journal of Sports Medicine (BJSM) to
      assess the nature of articles published, look at which specialities and
      nationalities were contributing most frequently, and analyse the numbers of
      subjects involved in the studies. METHODS: Data were collated from all original
      papers, review articles, and case reports from March 1991 to December 1995.
      RESULTS: Authors from 35 different countries contributed a total of 282 papers in
      the 5 year period, with medical authors (118) predominating. They covered a wide
      range of subjects in all aspects of sports medicine. There were few randomised
      controlled studies (9). CONCLUSIONS: The BJSM has wide international input which
      covers all aspects of sports medicine. A greater number of large randomised
      controlled studies would, however, provide a firmer statistical basis for future
      research and injury management. There is also scope for development of the BJSM
      especially in the areas of education, innovations, and the practical applications
      of research.

PMID- 9015603
TI  - Pneumomediastinum in a surf lifesaver.
AB  - Pneumomediastinum is an uncommon complication of sporting activity. The case of a
      young asthmatic surf lifesaver is reported in which several factors are thought
      to have been involved in the aetiology of his condition. Treatment was expectant
      and a full recovery was made over a short period. This is the first reported case
      of pneumomediastinum occurring following training for a surf belt race.

PMID- 9015604
TI  - Exercise induced leg pain-chronic compartment syndrome. Is the increase in intra
      compartment pressure exercise specific?
AB  - Intra-compartment pressure studies remain the main investigative method in
      diagnosing chronic compartment syndrome (CCS). Standard exercise protocols have
      been used to cause the raise in pressure measured in the laboratories. This case
      suggests that CCS cannot be excluded without the specific sports activity being
      used to raise the intracompartmental pressure.

PMID- 9015605
TI  - Late deterioration after decompression illness affecting the spinal cord.
AB  - A former amateur diver presented with a progressive paraparesis. Thirteen years
      previously he had developed acute spinal cord dysfunction immediately after dry
      hyperbaric exposure. He had completely recovered motor function in the
      intervening period. No alternative reason for the later decline emerged from
      detailed investigation.

PMID- 9015606
TI  - Extreme altitude transient aphasia.

PMID- 9015607
TI  - Clinical tests in sports medicine, Achilles tendon rupture.

PMID- 9015608
TI  - Verbal encouragement of voluntary muscle action: reply to commentary by Roger
      Eston.

PMID- 9015630
TI  - Neurosurgery in the past--the Dandy era.

PMID- 9015631
TI  - Neurosurgery of the present.

PMID- 9015633
TI  - Perspectives in neurosurgery.

PMID- 9015632
TI  - Neurosurgery of the future.

PMID- 9015634
TI  - Neurogenic intermittent claudication.

PMID- 9015635
TI  - Stenosis of the lumbar spinal canal.

PMID- 9015636
TI  - Space age biomedical research methods.

PMID- 9015637
TI  - New instrumentation for in vivo determinations of brain function.

PMID- 9015638
TI  - Towards a visual prosthesis.

PMID- 9015639
TI  - Monitors, ventilators, and the neurosurgeon.

PMID- 9015641
TI  - The surgical relief of pain.

PMID- 9015640
TI  - Phantom limb pain: concept of a central biasing mechanism.

PMID- 9015642
TI  - The cerebral microcirculation in man: analysis by radioisotopic microregional
      flow measurement and fluorescein angiography.

PMID- 9015643
TI  - Spontaneous intracerebral hemorrhage.

PMID- 9015644
TI  - Cerebral ischemia--less familiar types.

PMID- 9015645
TI  - Normal pressure hydrocephalus.

PMID- 9015646
TI  - Brain scanning--successes, limitations, and future developments.

PMID- 9015647
TI  - The physiology and treatment of shock due to volume loss (trauma), sepsis, or
      myocardial damage.

PMID- 9015649
TI  - Stress ulceration.

PMID- 9015648
TI  - Action of steroids on reduction of edema.

PMID- 9015650
TI  - The neurogenic bladder.

PMID- 9015651
TI  - Clinical aspects of coma.

PMID- 9015652
TI  - Brain monoamines in aggression and sleep.

PMID- 9015653
TI  - Psychophysiology of human sleep.

PMID- 9015655
TI  - Exercise increases insulin clearance in healthy man and insulin-dependent
      diabetes mellitus patients.
AB  - Exercise is known to decrease insulin secretion, but the effect on insulin
      clearance is unclear. We examined the effect of exercise in insulin clearance
      with euglycaemic insulin clamp in 28 healthy men either 12 h after a marathon run
      (n = 14) or 44 h after a 2-h treadmill exercise (n = 14), and in seven insulin
      dependent diabetes mellitus (IDDM) patients 12 h after a marathon run, and after
      a resting, control day. During the post-exercise insulin infusion, steady-state
      plasma insulin concentration was reduced by 9% in healthy men after both types of
      exercise, and by 16% in the diabetic subjects compared with the control study (P
      < 0.05 in all). In healthy men, C-peptide concentrations were more than one-third
      lower during insulin infusion, both after the marathon run (P < 0.001) or
      treadmill exercise (P < 0.02) compared with the control study. Insulin clearance
      was significantly increased by exercise both in healthy men (9% P < 0.05) and in
      IDDM subjects (15%, P < 0.05). After exercise, endogenous insulin secretion in
      healthy men is reduced and insulin clearance is enhanced both in healthy men and
      in IDDM patients. Decreased insulin availability may allow enhanced muscle lipid
      utilization and spare glucose after long-term exercise.

PMID- 9015654
TI  - Physiological characteristics and hormonal profile of young normotensive men with
      exaggerated blood pressure response to exercise.
AB  - Exaggerated blood pressure (BP) response to exercise in normotensive subjects is
      considered as a predictor of future hypertension. The aim of the study was to
      find out whether elevated BP response to exercise is associated with any other
      haemodynamic, metabolic or hormonal abnormalities. Abnormal BP response to
      exercise, i.e. systolic BP (SBP) > 200 mmHg at 150 W or lower workload, was found
      in 37 out of 180 normotensive, male students, aged 20-24 years. Fifteen students
      with elevated exercise BP (group E) volunteered for further examinations. Their
      resting and ambulatory BP showed high normal values. Eight of them had a family
      history of hypertension. Four subjects met the criteria of cardiac hypertrophy.
      Significant correlations were found between exercise SBP and left ventricular
      mass index, average 24 h and daytime SBP recordings. In comparison with normal
      subjects of the same age (group N, n = 13), those from group E did not differ in
      body mass index, plasma lipid profile, fasting glucose, insulin and catecholamine
      (CA) concentrations, but had increased erythrocyte sodium content, slightly
      elevated plasma renin activity and cortisol level. During exercise, E subjects
      showed greater cardiac output (CO) increases with normal heart rate, total
      peripheral resistance (TPR) and plasma CA. There were no significant differences
      between groups in haemodynamic and plasma CA responses to posture change from
      supine to standing. Glucose ingestion (75 g) caused smaller increases in CO and
      smaller decreases in TPR in E than in N subjects without differences in BP, blood
      glucose plasma insulin and CA. It is concluded that young normotensive men with
      exaggerated BP response to exercise show some other characteristics that may be
      considered as markers of predisposition to hypertension or factors promoting the
      development of hypertension.

PMID- 9015656
TI  - Influence of exercise training on heart rate variability in post-menopausal women
      with elevated arterial blood pressure.
AB  - Low heart rate variability (HRV) has been reported to be an independent risk
      factor for the development of coronary heart disease in women and has recently
      been identified as a risk factor for cardiac sudden death and all-cause
      mortality. We have recently demonstrated that endurance-trained post-menopausal
      women demonstrate higher levels of HRV than sedentary control subjects. The
      purpose of the present study was to test the hypothesis that 12 weeks of regular
      aerobic exercise would increase HRV in sedentary post-menopausal women with
      elevated arterial blood pressure (BP) (i.e. either high normal BP or stage I
      hypertension). A secondary aim was to test the hypothesis that the increase in
      HRV with exercise training, if observed, would be associated with an increase in
      spontaneous cardiac baroreflex sensitivity (SBRS), an important physiological
      determinant of HRV. To accomplish these aims, we studied eight sedentary post
      menopausal women (age = 54.5 +/- 1.3 years) before and after 12 weeks of aerobic
      exercise training (3.3 +/- 0.3 days per week at 70% +/- 2% of maximal heart rate
      for 43 +/- 3 min per day). Maximal oxygen uptake and body weight did not change
      (P > 0.05) with training, but percentage fat (35.5 +/- 2.6% vs. 34.5 +/- 2.3%, P
      < 0.05) decreased and treadmill time to exhaustion increased (9.8 +/- 0.5 vs.
      11.3 +/- 0.5 min, P < 0.05). Supine resting levels of heart rate, RR interval and
      the standard deviation of the RR interval (time domain measure of HRV) were
      unchanged (all P > 0.05) from baseline levels after 12 weeks of aerobic training.
      Similarly, the high-frequency, low-frequency and total power of HRV (frequency
      domain measures) were also unchanged from baseline (all P > 0.05). SBRS was also
      not different before and after aerobic exercise training (10 +/- 2 vs. 13 +/- 3
      ms mmHg-1 respectively, P > 0.05). In contrast, systolic and diastolic BP were
      reduced approximately 8 and approximately 5 mmHg with training (both P < 0.05)
      respectively. These results indicate that 12 weeks of moderate-intensity aerobic
      exercise training does not increase HRV or SBRS, despite producing a clinically
      significant reduction in BP at rest in post-menopausal women with elevated BP.
      Considered together with our previous findings in female master endurance
      athletes, these findings suggest that more intense and prolonged exercise
      training may be required to produce increases in HRV and SBRS in sedentary post
      menopausal women.

PMID- 9015657
TI  - Orthostatic tests after a 4-day confinement or simulated weightlessness.
AB  - Besides microgravity, inactivity is likely to play a role in the cardiovascular
      deconditioning after space flights and weightlessness simulations. The aim of the
      study was to compare the effects of a 4-day head-down bed rest (HDBR) (-6
      degrees) and a 4-day confinement (C) on cardiovascular responses to orthostatic
      stress. Eight male subjects underwent head-up tilt (HUT) (+60 degrees) and lower
      body negative pressure (LBNP) (-20, -30, -40 and -50 mmHg) before (D-1) and at
      the end (R1) of each situation. Blood pressure, heart rate variability (HRV) and
      spontaneous baroreflex slope (SBS) were determined. The HDBR reduced orthostatic
      tolerance, as five subjects presented orthostatic hypotension during the HUT at
      R1, compared with two subjects at D-1. These same two subjects presented
      orthostatic hypotension after confinement. The main findings, after HDBR,
      included reductions in RR interval and total spectral power and a decrease in the
      parasympathetic indicator (PNS) in favour of a decrease in vagal tone; the
      increase in the sympathetic indicator (SNS) was not significant. After
      confinement, the RR interval was also significantly reduced and PNS decreased,
      but not significantly. RR interval and PNS were further reduced during HUT and
      LBNP, reflecting a withdrawal of parasympathetic activity. SBS was reduced after
      HDBR (P < 0.05) and confinement (P = 0.05), with a further reduction during HUT
      and LBNP without difference between D-1 and R1. This experiment showed that a 4
      day HDBR leads to impaired baroreflex function and changes in autonomic balance,
      which may contribute to orthostatic intolerance. Although less significant,
      similar patterns of changes in the autonomic nervous system were observed after
      confinement, suggesting an influence of the inactivity in cardiovascular
      deconditioning.

PMID- 9015658
TI  - Renal functional reserve in pigs: renal haemodynamics, renal tubular function and
      salt and water homeostatic hormones during amino acid and dopamine stimulation.
AB  - The purpose of the study was to evaluate renal functional reserve [RFR is the
      difference between glomerular filtration rate (GFR) at rest and maximal GFR after
      stimulation] in a controlled study in normal pigs. Our basic hypothesis was that
      a decreased RFR may be used as an early indicator of renal deterioration, i.e. a
      test to disclose significant obstruction as opposed to simple dilatation in
      hydronephrosis. During various forms of stimulation (amino acids, captopril and
      dopamine), we measured changes in GFR, renal plasma flow (RPF), tubular
      reabsorption of sodium and water, net uptake from plasma to the kidney of three
      salt and water homeostatic hormones (angiotensin II, aldosterone and atrial
      natriuretic peptide) and of glucagon, which is thought to play a key role as
      mediator of the GFR increase during amino acid infusion. We found the largest GFR
      increase during combined infusion of amino acids and dopamine (+13%), but
      compared with a non-stimulated control group, the GFR increase was statistically
      non-significant. RPF increased by 57% during stimulation with amino acids plus
      dopamine (P < 0.001), while tubular reabsorption of sodium and water, and renal
      uptake of angiotensin II, aldosterone and atrial natriuretic peptide showed no
      significant differences between control and stimulation groups. The renal uptake
      of glucagon increased significantly during amino acid stimulation with no
      concomitant GFR increase. We conclude that in this experimental, non-obstructed
      model, RFR is a very insensitive measure, which cannot be used to discriminate
      between obstruction and simple dilatation in hydronephrosis. Further, our study
      does not support the hypothesis that glucagon is involved in GFR changes after
      amino acids.

PMID- 9015659
TI  - Skin temperature changes and changes in skin blood flow monitored with laser
      Doppler flowmetry and imaging: a methodological study in normal humans.
AB  - The aim of the present study was to elucidate the interrelation between changes
      in skin temperature and changes in skin blood flow, as measured by laser Doppler
      techniques. Therefore, 17 healthy volunteers were studied upon immersion of both
      feet in water of 15 degrees C for 10 min followed by body warming for 30 min.
      Measurements using laser Doppler flowmetery (LDF) were performed from the
      nailfold of the big toe, while measurements using laser Doppler imaging (LDI)
      were performed from the dorsum of the foot. Temperatures were recorded
      simultaneously from the toe tip and the dorsal foot skin. Temperatures at the toe
      tip were significantly lower than at the dorsal foot skin. Cooling caused
      decreased values in all parameters, with restitution during indirect heating.
      There was an exponential interrelation between LDF and temperature readings from
      the toe owing to very high LDF values at the end of indirect heating. On the
      dorsum of the foot, relative changes in LDI and temperature showed a linear
      relationship (rs = 0.65), although LDI values were consistently higher than
      temperatures. It is concluded that temperature readings constitute an ambiguous
      measure of skin blood flow. On the toe tip, blood flow through opened
      arteriovenous shunts during indirect heating does not correlate with temperature.
      Cooling of the foot decreases skin temperature, mainly by heat conduction,
      whereas skin blood flow is only slightly reduced.

PMID- 9015660
TI  - Cerebral and circulatory haemodynamics before vasovagal syncope induced by
      orthostatic stress.
AB  - Vasovagal syncope is usually described as a sudden and transient loss of
      consciousness that resolves spontaneously. Cardiocirculatory changes are well
      described during and before syncope. However, changes in the cerebral oxygenation
      are not well defined. In this study, near-infrared spectroscopy (NIRS) was used
      to assess the cerebral oxygenation directly during 80 degree head-up (HU) tilt.
      To simulate central hypovolaemia, 500 ml of blood was drawn from each of 10
      healthy subjects. Oxygenation index (OI) was defined as the difference between
      oxy- and deoxyhaemoglobin concentration. Blood pressure, heart rate and cardiac
      output were monitored using a finger plethysmographic device. The protocol was
      divided into two stages, each consisting of a 15-min stabilization period in the
      supine (SUP) position, 15 min in HU position and another 10 min in SUP position.
      Between both stages, blood was drawn from the subject. Haemoglobin concentration
      and haematocrit were measured before and 30 min after withdrawal of blood. No
      compensatory haemodilution was observed. During HU position in the second stage,
      six subjects showed signs of presyncope (F) and four did not (NF). A significant
      difference between F and NF was found in the observation that, before fainting,
      the OI of F showed a steady and significant (P = 0.02) decrease (-1.4 +/- 0.5
      microM min-1) compared with NF (-0.18 +/- 0.16 microM min-1). This indicates that
      the onset of (pre)syncope is preceded by a mismatch between oxygen demand and
      oxygen supply in the cerebrum. Using NIRS enabled us to monitor this mismatch and
      to predict the onset of a syncope before clear signs in cardiocirculatory
      variables were visible.

PMID- 9015661
TI  - Muscular activity of the shoulder and neck region during sustained and
      intermittent exercise.
AB  - Sustained isometric contractions of the neck and shoulder muscles in laboratory
      conditions are often assumed to be representative of muscular load in
      occupational tasks. The present study aims to investigate whether differences can
      be found between these contractions and those in intermittent tasks. Ten subjects
      performed forward flexions of the right arm during three tests to the limit of
      endurance: (1) a sustained contraction; (2) an intermittent contraction with a
      cycle time of 10 s and a duty cycle of 0.7; and (3) the same intermittent
      contraction with the possibility of changing the shoulder angle during
      relaxation. Muscular activities of the upper trapezius, deltoid pars anterior and
      medialis and infraspinatus were registered using surface electromyography, and
      changes in the signal were quantified by root mean square (RMS) and mean power
      frequency (MPF) values. During the continuous test, highly significant changes in
      both parameters were found for the four muscles. Significant changes were found
      during both intermittent conditions, although to a lesser degree than in the
      continuous test. Significant differences between the regression coefficients of
      the sustained test and the two intermittent tests were found on all occasions:
      for RMS and MPF of the four muscles. Significant differences were also found
      regarding the intermittent tests. The test in which no variation in limb position
      was allowed during relaxation caused a more pronounced MPF decrease for the
      trapezius (P < or = 0.01), which was confirmed by the subjective scores of
      perceived exertion and a higher RMS increase (P < or = 0.01) for the middle part
      of the deltoid. The intermittent condition with changes in shoulder angle showed
      more MPF decrease for the deltoid, significant for the middle part (P < or =
      0.05), not significant for the anterior part and a larger RMS increase for
      infraspinatus (P < or = 0.05). It can be concluded that the latter condition
      represents more the trapezius and deltoid activity as in occupational tasks.

PMID- 9015662
TI  - Effects of compression bandaging on leg pulsatile blood flow.
AB  - Leg external compression bandaging is the mainstay of venous ulcer treatment, yet
      little is known about the impact of therapeutic compression levels on arterial
      haemodynamics. In this study, the effect of foot-to-knee, four-layer compression
      bandaging on below-knee arterial pulsatile blood flow was assessed by nuclear
      magnetic resonance flowmetry. In 14 healthy supine subjects bilateral flow
      measurements at five below-knee sites without compression, and after compressing
      one leg to an average malleolar sub-bandage pressure of 40.7 +/- 4.0 mmHg,
      revealed a potentially important new phenomenon. The forefoot-to-knee compression
      bandaging caused a highly significant (P < 0.001) increase in the bandaged leg
      pulsatile blood flow owing to increases in both peak flow and pulse width. It is
      hypothesized that arteriolar vasodilatation, induced either myogenically by
      reduced transmural pressure or by vasodilatory substance release triggered by
      increased venous shear stress, produce the observed compression-related
      phenomenon. Whatever the mechanism(s), the finding of a compression-associated
      pulsatile flow increase suggests a previously undiscovered arterial linkage,
      which may play a role in the well-documented beneficial effects of compression
      bandaging in venous ulcer treatment. A possible impact of the arterial flow-pulse
      increase is speculated to effect venous ulcer outcome via a decrease in leucocyte
      effects in the distal microvasculature, as a consequence of the more vigorous
      haemodynamic state.

PMID- 9015663
TI  - The WHO national diabetes programme initiative.
AB  - Epidemiological studies indicate that diabetes is a highly prevalent disease,
      with developing countries and minority populations now facing the highest risk.
      This places a strain on the health authorities, and consequently, has attracted
      increasing attention from the World Health Organization (WHO). The social and
      economic burden of diabetes is high, due to the seriousness of the complication
      of the disease. Many of these complications may be delayed or prevented, offering
      considerable opportunities for both reduction in costs to the authorities and
      improvements in quality of life for those affected. Following a resolution on the
      prevention and control of diabetes, adopted by the Forty-second World Health
      Assembly in 1989, the WHO diabetes programme prepared guidelines for the
      development of national diabetes programmes. Goals, targets and supporting
      materials have also been developed at the regional level by the WHO Regional
      Offices for Europe and for the Eastern Mediterranean. In 1994, WHO organized a
      meeting on the implementation of national diabetes programmes at its headquarters
      in Geneva. There were 70 participants and 32 counties were represented. The
      purposes of the meeting were to exchange information, motivate, consider
      evaluation, stimulate new programmes, define educational needs and prepare a
      written report. WHO plays a major role in the development of national diabetes
      programmes. In co-operation, WHO Headquarters and Regional Offices can act as
      clearing houses/information centres for data collection, programme monitoring and
      evaluation and the exchange of experience and technical information. The national
      diabetes programme initiative should result in improvements in diabetes control
      and care worldwide.

PMID- 9015664
TI  - Prediction of diabetes mellitus (NIDDM).
AB  - This study was made to analyze predictive NIDDM markers using a long-term GTT
      follow-up observation period of 1-30 years. Subjects of this study were 5446
      cases (3994 males, 1452 females). Results are as follows: (1) NIDDM development
      rate increased gradually with increasing 2 h-PG levels at GTT, but for groups
      with 2 h-PG > or = 170 mg/dl, the rate rose rapidly. (2) PG at GTT was higher in
      the NIDDM development group than in the control group. Mean 1 h-PG reached > or =
      200 mg/dl for 4 years before onset in the NIDDM group. Frequency of 1 h-PG > or =
      200 mg/dl was 54% 4 years before and 67% 1 year before onset. (3) The highest
      NIDDM prediction accuracy was in 1 h-PG levels of 200 mg/dl or more and/or 2 h-PG
      levels of 170 mg/dl or more. Sensitivity was 75.2%, and specificity, 63.4% within
      3 years before onset. (4) With addition of delta IRI/delta PG, sensitivity
      increased, but specificity decreased. (5) The highest relationship with NIDDM
      development was for high PG levels (1 h-PG > or = 200 mg/dl and/or 2 h-PG > or =
      170 mg/dl), the odds ratio being 5.65. The odds ratio of delta IRI/delta PG was
      lower than ratio of high PG levels. (6) NIDDM development rate increased about
      50% in the under-60-years age group and in the group of BMI > or = 25.

PMID- 9015665
TI  - The significance of a positive family history in South African Indians with non
      insulin-dependent diabetes (NIDDM).
AB  - A group of South African Indians with NIDDM participated in a study to evaluate
      the frequency of positive family histories of the disease and to determine the
      relative contribution of maternal or paternal genetic determinants. Information
      was elicited by means of an interview and recorded. Of the 1098 diabetic subjects
      studied 70% gave a positive family history of a first degree relative suffering
      from NIDDM. Three-generation transmission was recorded in 5.3% of the subjects. A
      significantly greater proportion of probands (40%) had a mother with NIDDM than
      those with a father (26%). A positive family history in an offspring was more
      common in female probands (10.6%) than males (5.5%). Twice as many probands with
      3 generation transmission had a maternal grandmother suffering from NIDDM (2.5%)
      compared with those who had a paternal grandmother afflicted (1.2%) (P < 0.05),
      whereas the frequencies in the maternal (0.9%) and paternal (0.8%) grandfathers
      were similar. This study has highlighted, not only the high prevalence of a
      positive family history in South African Indians with NIDDM, but also a stronger
      maternal contribution to the putative gene responsible for the disease.

PMID- 9015666
TI  - Population screening for glucose intolerant subjects using decision tree
      analyses.
AB  - The purpose of this study was to develop a method of screening for impaired
      glucose tolerance and previously undiagnosed NIDDM that could be used preliminary
      to the administration of an oral glucose tolerance test (OGTT) for final
      classification of glucose tolerance status. The purpose of a preliminary
      screening of this type would be to reduce the number of OGTT's needed to identify
      cases of IGT and NIDDM in the population. We used NIDDM risk indicators and
      decision tree analysis methods (CART software) to identify subgroups of the
      population at increased risk. We examined a population of Hispanic (n = 583) and
      non-Hispanic white (n = 768) subjects without a prior history of diabetes.
      Subjects were classified as normal, IGT or NIDDM (WHO criteria) based on results
      from a 75 g oral glucose tolerance test (OGTT). Sensitivity (SEN) and specificity
      (SPE) of the CART models were calculated using the OGTT as the 'gold standard.'
      Two approaches to screening were simulated. In the simultaneous approach all risk
      variables were entered into CART models at once. In the serial approach, risk
      variables were grouped according to degree of effort required for data
      collection, and were entered into CART models in stages. Fasting glucose, age and
      body mass index (BMI) were selected as risk variables by CART when simulating the
      simultaneous approach (SEN = 91%, SPE = 55%). In the serial approach, CART used
      age and BMI to eliminate 35% of the population from further screening, and then
      used fasting glucose, glycohemoglobin, age and BMI to classify the remaining
      higher risk subjects (SEN = 85%, SPE = 64%). These models suggest that screening
      for IGT and previously undiagnosed NIDDM can be based on measurement of
      relatively simple indicators, and yet maintain a level of both sensitivity and
      specificity acceptable for this type of preliminary screening.

PMID- 9015667
TI  - Proinsulin and insulin levels according to glucose tolerance among Japanese
      Brazilians, aged 40-79 years. Japanese-Brazilian Diabetes Study Group.
AB  - This study of the Japanese-Brazilians living in Bauru, Sao Paulo, Brazil, aimed
      at determining the prevalence of DM in the first (Issei) and second (Nisei)
      generations, according to WHO criteria. Insulin and proinsulin were determined by
      new immunofluorimetric assays (IMFA), that measure true insulin and intact
      proinsulin, at fasting and 2 h after glucose load. The data showed a very
      scattered distribution, so only medians are shown and no statistical testing
      applied. There was a tendency for higher proinsulin levels in the diabetic
      groups. The highest fasting proinsulin levels were seen in the diabetic patients,
      either obese or non-obese. The post-load insulin levels were higher in diabetic
      and IGT individuals, compared to normals. Both generations showed a distinct
      behaviour for the obese and non-obese groups, and no major differences were
      observed between generations. This population seems to be sensitive to
      environmental changes, since the obese groups showed the higher levels of
      proinsulin and insulin. In the evaluation of the role of the environmental
      factors in the pathogenesis of DM, proinsulin and insulin levels could act as
      early markers of pancreatic dysfunctions.

PMID- 9015668
TI  - Low prevalence of immunogenetic markers of IDDM in adult Koreans with diabetes
      detected on OGTT.
AB  - In the Asian populations, it is not uncommon for adult patients with NIDDM to
      eventually lose beta-cell function and develop IDDM. Accepting that IDDM is an
      autoimmune disease, which occurs on a genetic background, it could by
      hypothesized that by measuring autoantibody prevalence and HLA DQ gene
      polymorphism, known important prediagnostic markers of IDDM, the prevalence of
      adult-onset IDDM in patients with previously undiagnosed NIDDM patients could be
      estimated. To do this, anti-GAD prevalence and HLA DQ A1 and DQ B1 polymorphisms
      after PCR amplification of genomic DNA were analyzed in 121 newly diagnosed
      diabetic patients of Yonchon cohort and compared to the results with those of 100
      matched health control subjects. We also compared the results with those of other
      populations to assess the difference of genotype distribution. The overall
      prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously
      undiagnosed NIDDM, whereas 1 of 100 controls had positive antibodies. Among those
      who were positive, their titer of antibodies to GAD were not high. No
      statistically significant differences in the distribution of either mean levels
      of anti-GAD or DQA1 and DQB1 alleles were found comparing NIDDM patients to
      controls. Interestingly, the frequency of DQB1*non-Asp-57 and DQA1*Arg-52 alleles
      in the Korean adult control population was similar to that of US Caucasians
      (DQB1*non-Asp-57: 0.431 vs. 0.475; DQA1*Arg-52: 0.492 vs. 0.463). The low
      prevalence of anti-GAD antibodies and HLA-DQA1 and DQB1 susceptibility alleles
      among recent-onset NIDDM patients, not different compared to controls suggests
      that diabetes in Korean adults is unlikely to have an autoimmune component to its
      pathogenesis.

PMID- 9015669
TI  - Incidence of NIDDM and the natural history of IGT in Pacific and Indian Ocean
      populations.
AB  - The prevalence of both NIDDM and IGT vary considerably within and between
      developing island populations of the Pacific and Indian Ocean regions.
      Longitudinal data have been collected recently in a number of these populations,
      allowing incidence rates to be compared. The incidence of NIDDM in adults ranged
      from a low of 1.2/1000 person-years (p.y.) in peri-urban and rural Papua New
      Guinea (PNG) Highlanders to 22.5/1000 p.y. in Micronesian Nauruans and 24.0/1000
      p.y. in the rural Wanigelas of coastal PNG. Intermediate rates were observed in
      Polynesian Western Samoans (16.6 and 5.7/1000 p.y. in urban and rural areas,
      respectively) and ethnically diverse Mauritians: Asian Indians (15.8), African
      origin Creoles (12.2), and Chinese (10.4/1000 p.y.). When stratified by age and
      body mass index (BMI), incidence in Wanigelas exceeded rates observed in Pima
      Indians, and rates in Mauritians were higher than those of Nauruans. For subjects
      with IGT at baseline, rates of conversion to NIDDM ranged from 19.0 to 102.6/1000
      p.y. Particularly after stratifying for age and body mass index, it was apparent
      that there was less variation between populations in rates of decompensation from
      IGT than was observed for total incidence. The relative risk of conversion to
      NIDDM for IGT versus normal subjects ranged from 2.1 in urban Samoans to 7.6 in
      Nauruans, but most estimates exceeded 5.

PMID- 9015670
TI  - Diabetes in Japanese-Brazilians--influence of the acculturation process.
AB  - Epidemiologic studies of migrant populations provide very promising clues towards
      understanding the roles of genetics and environmental factors in the etiology of
      diabetes mellitus. Populations of Japanese ancestry are of particular interest
      due to marked differences in prevalence rates of non-insulin dependent diabetes
      (NIDDM) when comparing those living in Japan with those who migrated to western
      countries. Brazil offers very favorable conditions of the study of diabetes in
      the Japanese origin population. Presently, Brazil has the largest population of
      Japanese ancestry outside Japan. A cross-sectional study comparing first (Issei)
      and second (Nisei) generations of Japanese-Brazilians living in the city of
      Bauru, in the industrialized state of Sao Paulo, southeast of Brazil, was carried
      out between May and November 1993. The study sample consisted of all first
      generation (127 men and 111 women) and a random sample of second generation (136
      men and 156 women) aged 40-79 years. Results show that: 1--The prevalence of
      diabetes in Japanese Brazilians (12.8 and 16.2% for first and second generations)
      are higher than the rates reported for Japan at comparable age-groups. 2-
      Comparing generations, the age-adjusted prevalence of diabetes was higher in the
      second generation only for men (men: 12.4 vs. 21.7%; women: 11.6 vs. 11.4%). 3-
      Obesity was more prevalent in the second generation among men (Men: 34.6 vs.
      45.7% women, 39.6 vs. 40.8%).

PMID- 9015671
TI  - Disturbances of glucose and lipid metabolism in first and second generation
      Japanese-Brazilians. Japanese-Brazilian Diabetes Study Group.
AB  - Increased prevalence of self-reported NIDDM in Japanese-Brazilians was reported
      when compared to Japan. This study aimed at determining the prevalence of NIDDM
      and IGT in Japanese-Brazilians living in the city of Bauru, Sao Paulo, Brazil.
      The impact of western environment on the frequency of obesity, dyslipidemia and
      hypertension was investigated. All Issei (first generation; n = 238) and a random
      sample of Nisei (second generation; n = 292), aged 40-79 years, were selected for
      clinical examination and OGTT (WHO criteria). Age-adjusted prevalence of NIDDM
      did not differ between men and women for Issei (12.4 vs. 11.6%, respectively),
      but it became different for Nisei (21.7 vs. 11.4%, P < 0.03) due to an increased
      rate among men. Increased IGT prevalence was also observed between Issei and
      Nisei men (8.5 vs. 19.3%, P < 0.03). Issei women had a higher IGT rate than Issei
      men (27. 3 vs. 8.5%, P < 0.0005). Body mass index (BMI) was higher in the second
      generation (24.1 +/- 3.6 vs. 23.3 +/- 3.1 kg/m2, P < 0.00005) and also the
      frequency of obesity, defined as BMI > 25 kg/m2. Comparison of waist/hip ratio by
      gender showed that only among women, Nisei had lower ratio than Issei (0.90 vs.
      0.88, P < 0.05). Nisei had a lower total and LDL-cholesterol than Issei but
      triglyceride and HDL-cholesterol did not differ. Nisei women (younger than the
      Issei) had lower triglyceride and total cholesterol. This pattern was not seen
      between the two generations of men. Considering the mean blood pressure values,
      Issei and Nisei groups with normal glucose tolerance were not hypertensive.
      Systolic blood pressure was lower in Nisei and the inverse was found concerning
      diastolic levels. NIDDM prevalence in Japanese-Brazilians is higher than in Japan
      and in the general Brazilian population. Besides environment, genetic factors may
      confer susceptibility to NIDDM when they are exposed to a western environment.
      Before developing glucose intolerance, disturbances of lipid profile and blood
      pressure could be detected. Nisei may be more affected due to a longer exposure
      to an unfavorable environment and these changes seem to occur earlier among men
      than women.

PMID- 9015672
TI  - Community-based epidemiologic study on atherosclerotic cardiovascular risk
      factors.
AB  - The present study was undertaken to determine the prevalence of hyperlipidemia
      and to find out the possible impact of serum lipid profiles on other
      cardiovascular risk factors in Yonchon County, Korea. Population-based cross
      sectional study by random cluster sampling of registered residents over 30 years
      of age was performed. Out of the 3804 subjects scheduled for the survey, 2520
      underwent the actual examination. The prevalence of hypercholesterolemia (serum
      cholesterol > or = 240 mg/dl) was only 1.2%, whereas that of hypertriglyceridemia
      (serum triglyceride > or = 250 mg/dl) was as high as 11.3%. The serum levels of
      cholesterol, triglyceride and HDL cholesterol correlated with anthropometric
      indices, body mass indices and waist hip ratios. The prevalences of diabetes
      and/or hypertension increased as either serum cholesterol or triglyceride level
      increased. In addition, the prevalence rates of obesity, impaired glucose
      tolerance, hypertriglyceridemia and hypercholesterolemia in its isolated form
      (free of the others) were much lower than overall prevalence indicating an
      existence of major overlap among these cardiovascular atherosclerotic risk
      factors in the form of multiple combinations. Central obesity was found to be an
      independent associated factor for the aggregation of the conditions related to
      the increase in cardiovascular risks. The prevalence of hypercholesterolemia in
      Yonchon County was substantially lower than that previously suggested, albeit
      that of hypertriglyceridemia was very high. We could also observe a varying
      degree of transition in cardiovascular risks related to insulin resistance from
      the rural to the urban area with rapid emergence of non-communicable diseases as
      a result of modernization.

PMID- 9015673
TI  - Prevalence of diabetes mellitus and its complications in the Ukraine.
AB  - Analysis of the prevalence of insulin-dependent diabetes mellitus (IDDM) and non
      insulin-dependent diabetes mellitus (NIDDM) in various climato-geographic and
      administrative regions of the Ukraine was performed. The prevalence of diabetes
      mellitus (DM) complication in the west and north zones of the Ukraine was
      studied. The role of prophylactic measures in decreasing the number of
      complications was elucidated. The statistical reports from the specialized
      endocrinologic institutions of the Ukraine were analysed in the Laboratory of
      Epidemiology of Endocrine disease of Institute and results from 3450 and 673
      diabetic patients in the west and north zone of the Ukraine were used,
      respectively. In various administrative regions of the Ukraine the prevalence of
      IDDM significantly varied from 1740 to 3813 patients per 1 million population.
      Significant differences in the prevalence of NIDDM were found. Generally in the
      west zone of the Ukraine the prevalence of DM was less than that of average in
      the Ukraine. Angiopathy of the lower extremities, neuropathy and retinopathy were
      registered in 92, 24, and 21% of diabetes cases in the west zone, respectively.
      Prophylactic measures directed at a decrease in patient weight, the normalization
      of metabolism, arterial pressure and the elimination of pernicious habits
      promoted a decrease in the number of complications.

PMID- 9015674
TI  - The frequencies of diabetic complications in elderly non-insulin dependent
      diabetic patients in Himeji.
AB  - Data on 746 patients with non-insulin-dependent diabetes mellitus (NIDDM) were
      collected from the Internal Medical Association in Himeji by questionnaire, and
      the patients were divided into six groups according to the duration of illness.
      Frequencies of various complications according to the duration of illness and
      risk factors of complications were compared between men and women. Although the
      number of male patients was 417, significantly more than the 329 female patients,
      many female patients were elderly, and the age at initial onset was about 10
      years older than that of the male patients. Fasting blood sugar and hemoglobin
      A1c levels increased with the duration of illness. The female patients showed a
      greater tendency to suffer from hypertension, hyperlipidemia and obesity than the
      male patients. There was positive correlation between the incidence of
      complications and duration of illness. This tendency was more marked in the
      female patients than in the male patients. Both male and female patients showed a
      tendency for microangiopathy to appear earlier than macroangiopathy. The increase
      in the frequency of complications accompanying the increase in the duration of
      illness was more marked for microangiopathy than for macroangiopathy.

PMID- 9015675
TI  - Diabetes monitoring system in The Netherlands.
AB  - Under the aegis of the European Regional Offices of the World Health Organization
      (WHO) and the International Diabetes Federation (IDF) a joint action programme to
      contest the growing burden of diabetes has been drawn up. The St. Vincent
      Declaration (1980) specifies targets for diabetes care, the reduction of
      complications, the integration into society and the education of the diabetic
      individual. The WHO/IDF have drawn up a data set to monitor progress in reaching
      the targets of the St. Vincent Declaration. The objective of the project Diabetes
      Monitoring System is to examine the possibilities for implementing a longitudinal
      based and standardised diabetes monitoring system in the Netherlands. Although
      computerised recording systems for diabetes are seldom used and the agreement
      with the WHO/IDF data set varies substantially, the willingness of physicians to
      participate is clearly sufficient. This principally explorative project will
      hopefully lead to the implementation of a monitoring system in which a widely
      accepted data set is recorded to establish improvements in quality of care and to
      perform epidemiological research.

PMID- 9015676
TI  - Ethnic differences in diabetes care in a multiethnic community in New Zealand.
AB  - Residents of two districts of South Auckland, New Zealand with a high proportion
      of Maori and Pacific Islands people were visited door to door to ascertain the
      prevalence of known diabetes and its tissue damage. The household survey
      canvassed 55,518 residents in 12,770 (91%) of 14,002 residences. Diabetes
      interviews were available for 176,214 (82%) Europeans, 286,336 (85%) Maori and
      495,585 (85%) Pacific Islands diabetic patients. Europeans were older than Maori
      and Pacific Islands patients currently and at diagnosis. When compared with
      Europeans, Maori and Pacific Islands patients had a higher chance of having had
      their diabetes diagnosed in pregnancy, were least likely to be receiving
      antihypertensive or insulin therapy, were more likely to be blind, and were more
      likely to have received retinal photocoagulation. There were no ethnic
      differences in either the proportion of those receiving no ongoing care or in the
      proportion seen at least once by the diabetes services. Maori people were most
      likely to be current smokers, were most likely to have defaulted from the
      diabetic diet and to be dissatisfied with the diabetes service. Pacific Islands
      people were least likely to have neuropathic symptoms in their feet or to report
      a known myocardial infarction. Significant ethnic differences in diabetes and its
      care exist in South Auckland.

PMID- 9015677
TI  - Diabetes prevention in American Indians and Alaska Natives: where are we in 1994?
AB  - American Indians and Alaska Natives have experienced rapidly increasing rates of
      non-insulin-dependent diabetes (NIDDM). To address this epidemic Indian Health
      Service (IHS) and tribal communities have developed primary, second and tertiary
      intervention strategies. The scientific basis for secondary and tertiary
      prevention supports well-defined care practices, and the surveillance of the
      implementation of these practices and their impact on metabolic and hypertension
      control is now standard. Community interventions for the primary prevention of
      diabetes are underway and reflect the priorities of individual communities.

PMID- 9015678
TI  - Prevention of IDDM: the genetic epidemiologic perspective .
AB  - Rational prevention of insulin-dependent diabetes mellitus (IDDM) requires
      knowledge about the aetiology and pathogenesis of the disease. The causation of
      IDDM is complex, involving genetic susceptibility as well as non-genetic
      determinants. The evidence of a genetic component to IDDM is based on the high
      concordance rate in monozygotic twins as compared with dizygotic twins, the
      higher recurrence risk among relatives of patients with IDDM as compared with the
      general population risk, and the well-established associations with genetic
      markers, including specific alleles from the HLA-locus. The evidence of a non
      genetic component to IDDM is primarily based on the fact that the concordance
      rate in monozygotic twins is far from unity; the huge geographical variation in
      the incidence of IDDM, even between genetically similar populations, and the
      increasing incidence in many populations provide further support; associations
      between the risk of developing IDDM and exposure to several non-genetic
      determinants, including nutrients and viral infections, have been established and
      serve as additional evidence. In general, the relative risks conferred by the non
      genetic determinants are rather small, and it is unknown how these factors
      initiate the autoimmune-mediated process that destroys the beta-cells of the
      pancreas. Recent findings suggest that non-genetic factors interact with genetic
      susceptibility genes in the causation of IDDM. Firstly, it appears that the
      increase in the incidence of IDDM has predominantly been observed in populations
      with high frequency of susceptibility genes. Secondly, it seems that the risk of
      IDDM among relatives of patients with IDDM is positively correlated with the
      general population risk level. All these lines of evidence considered together
      suggest that IDDM may develop from several different combinations of
      susceptibility genes acting together with non-genetic exposures. If so,
      prevention of IDDM will require assessment of disease risk at individual rather
      than at population level. Since genetic screening is neither feasible nor
      ethically acceptable in the population at large, possible prevention of IDDM will
      be restricted to individuals who, by means of a positive family history, may be
      classified as being at high disease risk.

PMID- 9015679
TI  - Molecular IDDM epidemiology: international studies. WHO DiaMond Molecular
      Epidemiology Sub-Project Group.
AB  - The WHO DiaMond Molecular Epidemiology Sub-Project is testing the hypothesis that
      the geographic differences in IDDM incidence reflect population variation in the
      frequency of IDDM susceptibility genes (i.e., DQA1 and DQB1 alleles with
      sequences coding for arginine (R) in position 52 of the DQ alpha-chain, and an
      amino acid other than aspartic acid (ND) in position 57 of the DQ beta-chain,
      respectively) using a standardized case-control design. Data from twelve
      populations which have completed (or have nearly completed) recruitment and HLA
      molecular analyses are presented. There was an approximate 2-fold increase in the
      frequencies of DGA1*0301, DQB1*0201 and DQB11*0302 among IDDM cases compared to
      non-diabetic controls in most populations. Interestingly, DQA*0301 was more
      common in low versus moderate-high incidence countries. DQB1*0201 and DQB1*0302
      were more prevalent in the moderate-high incidence areas. DQA1*R and DQB1*ND were
      both consistent markers of IDDM risk, with stronger associations in moderate-high
      versus low incidence areas. In general, individuals homozygous for both DQA1*R
      and DQB1*ND had the highest genotype-specific IDDM incidence rates, which
      approximated risk estimates for first degree relatives in several countries.
      These data revealed considerable variation in the frequencies of DQB1 and DQA1
      alleles across countries, which likely contribute to the global patterns of IDDM
      incidence.

PMID- 9015680
TI  - Molecular epidemiology of IDDM in the Western Pacific Rim Region. WHO DiaMond
      Molecular Epidemiology Sub-Project Group.
AB  - HLA-DQA11 and DQB1 alleles coding for arginine (R) in position 52, and an amino
      acid other than aspartic acid (ND) in position 57, respectively, are strong
      genetic markers for IDDM in Caucasians. However, their contribution to the
      occurrence of the disease in Asian populations is less clear. As part of the WHO
      DiaMond Molecular Epidemiology Sub-Project, HLA-DQ molecular typing was performed
      for IDDM cases and non-diabetic controls from three populations in the Western
      Pacific Rim Region where incidence rates have been established (Hokkaido, Japan;
      Seoul, Korea; Auckland, New Zealand). DQA1*R homozygosity was significantly
      associated with IDDM in all areas. DQB1*ND homozygosity was also related to IDDM
      in Korea and New Zealand, but not in Japan. Individuals who were homozygous for
      DQA1*R and DQB1*ND were at highest IDDM risk in Korea and New Zealand, with the
      most striking findings in Auckland. In Japan, individuals carrying two DQA1*R,
      but only one DQB1*ND allele, were most likely to develop IDDM. These data
      revealed considerable genetic heterogeneity between Japan and Korea and suggest
      that DQA1*R and DQB1*ND alleles may explain a larger proportion of IDDM incidence
      in Caucasian compared to Asian populations.

PMID- 9015681
TI  - Antibodies to glutamic acid decarboxylase in the prediction of insulin
      dependency.
AB  - Antibodies to glutamic acid decarboxylase (anti-GAD) predict the progression of
      adults masquerading as NIDDM to insulin dependency and predict the eventual
      occurrence of IDDM in healthy pregnant women in Finland. Almost 80% of
      prediabetic and newly diagnosed IDDM cases are positive for anti-GAD. However,
      approximately 20% of these groups do not have a humoral response to GAD so it
      cannot be claimed that anti-GAD is the exclusive autoimmune phenomenon.
      Nevertheless, 94% of children with newly diagnosed IDDM that we studied had an
      autoimmune response to either GAD, ICA or IAA, singly or in combination. The anti
      GAD assay also has a substantial role in the diagnosis and classification of
      diabetes presenting in adult life since a proportion of adults who present with
      apparent NIDDM actually have a slowly evolving autoimmune insulitis, a condition
      we have called latent autoimmune diabetes in adults (LADA). It appears likely
      that anti-GAD will be predictive for IDDM in both first degree relatives and the
      general population. As a result of the cost and relative ease of performance, it
      will provide a practical alternative to ICA, particularly in population
      screening. Comparisons of testing for anti-GAD and ICA as predictors of IDDM
      using large population groups are now in progress in our laboratory.

PMID- 9015682
TI  - HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes
      mellitus.
AB  - The differential antibody response to glutamic acid decarboxylase (anti-GAD) and
      to islet cell cytoplasm (ICA) according to HLA-DR and DQ genotypes were examined
      in 28 Spanish patients with Type I diabetes mellitus (11.1 +/- 10.4 year diabetes
      duration) and their 41 first degree non-diabetic relatives. Anti-GAD was detected
      by radioimmunoprecipitation and ICA by indirect immunofluorescence and HLA-DR/DQ
      alleles were assigned by PCR and sequence specific oligonucleotide probes. The
      frequency in patients of positivity for ICA was 7.1% and of anti-GAD+ 64.3%, and
      in relatives, the frequency of ICA+ was 4.9%, and anti-GAD+ 9.8%. Concurrent
      positivity for ICA and anti-GAD existed in only one patient, and in none of the
      relatives. We confirm for a Spanish population the high frequency of risk
      genotypes for Type I, involving DR3, DR4 and DQB1*0302 (DQ8) which were present
      in 26 of 28 (93%) patients and 32 of 41 (78%) relatives. The most frequent
      genotypes were DR3/DQB1*0201/DQA1*0501-DR4/DQB1*0302/DQA1*0301( 9 patients, 32%;
      6 relatives, 15%), DR3/DQB1*0201/ DQA1*0501-DR3/DQB1*0201/DQA1*0501 (5 patients,
      18%; 7 relatives, 17%) and DE3/DQB1*0201/DQA1*0501-DR1/ DQB1*0501/DQA1*0101(5
      patients, 18%; 1 relative, 2%). Positivity for anti-GAD or for ICA did not
      correlate with gender, or age at onset or duration of DM. The distribution of
      high risk HLA genotypes were similar regardless the anti-GAD or anti-ICA status
      either in patients or in their relatives.

PMID- 9015683
TI  - Calendar time trends of the insulin-dependent diabetes mellitus mortality in
      Allegheny county, Pennsylvania.
AB  - This study applied a Cox proportional hazard model to investigate the calendar
      time trends of insulin-dependent diabetes mellitus (IDDM) mortality. The study
      population was the IDDM patients who were diagnosed in the period 1965-1979, less
      than or equal to 19 years of age at diagnosis, and were residents of Allegheny
      County, PA. The mortality follow-up for each individual was recorded from the
      diagnosis of IDDM and till 31 December 1990. There were 999 individuals in this
      study, and 68 deaths (6.8%) occurred during this 26-year investigation period.
      Overall, for the patients with the same IDDM duration, non-whites were 1.7 times
      more likely to die than white group; female IDDM patients had a higher risk of
      death than male IDDM patients (1.27:1); and the risk of mortality increased as
      the age at diagnosis increased. When controlling for the gender, ethnic groups
      and age at onset effect, the risk of dying in different calendar years appeared
      to be a quadratic form. The highest mortality appeared in the late 60's, and the
      lowest was in the period of 1975-1979. Disappointingly the mortality has begun to
      rise again in the latest time frame.

PMID- 9015684
TI  - Incidence of insulin-dependent diabetes mellitus in the IX region of Chile:
      ethnic differences.
AB  - We studied the incidence of insulin-dependent diabetes mellitus (IDDM) among
      children up to 15 years old of Caucasian and Mapuche origin, in the IX Region of
      Chile between 1980 and 1993. The Mapuche, or native Chileans, have their own
      culture, language an distinctive ethnic characteristics. Data were collected
      according to the methods recommended by the Diabetes Epidemiology Research
      International Group. We diagnosed IDDM in 47 children, 22 boys and 25 girls. The
      average annual incidence was 1.27/100,000 inhabitants (95% confidence intervals
      (C.I.) 0.83-1.71/100,000). The highest incidence along this period was during
      winter and spring. There was significant difference (P < 0.0016) in the IDDM
      incidence in Caucasians (1.58/100,000, 95% C.I. 1.11-2.04) compared with Mapuche
      (0.42/100,000, 95% C.I. 0-0.95). These results show that Mapuche children have
      less chance of developing diabetes.

PMID- 9015685
TI  - One of the lowest validated incidence rates of insulin dependent diabetes
      mellitus in the Americas: Santiago, Chile.
AB  - The goal of this study was to estimate the average annual incidence rate of
      insulin-dependent diabetes mellitus (IDDM) in Santiago as part of a Multinational
      Project in Childhood Diabetes (Diabetes Mondiale or DiaMond). Incidence was
      calculated among subjects under 15 years of age, through a retrospective search
      and confirmation method from 1 January 1986 to 31 December 1992. Hospitals and
      private offices of endocrinologists and specialists in diabetes were surveyed. A
      total of 252 registered cases, 118 boys and 134 girls, for an annual incidences
      of 2.36/100,000 hab.year. which is one of the lowest validated rates in the
      Americas.

PMID- 9015686
TI  - Clinical and laboratory characteristics of type I (insulin dependent) diabetes
      mellitus at presentation among Bulgarian children.
AB  - Clinical and laboratory data of 1248 newly diagnosed diabetic children at the
      time of diagnosis were analysed. All children were admitted to the University
      Children's Hospital in Sofia, 45.9% before first their insulin injection.
      Symptoms preceding the diagnosis and laboratory data (plasma glucose and
      ketonuria) were analysed, respectively for 1100 and 1022 children. Blood pH
      (mainly arterialized) was available in 558 ketonuria positive children and in
      other 82 acidotic breathing was reported. Mother's education was noted in the
      1226 hospital records. Among the children with known urinanalysis 13.5% were
      without ketonuria (148 patients), 12 of them with fasting blood glucose < or =
      6.4 mmol/1 (115 mg/dl). Eighteen-point-two percent of all children were
      hospitalized in a state of severe ketoacidosis (blood pH < or = 7.2 or reported
      acidotic breathing). The average duration of thirst and polyuria was 28 +/- 33
      days. Ketonuria negative children with plasma glucose < or = 6.4 mmol/l showed a
      significantly shorter period of symptoms, compared to those with plasma glucose >
      6.4 mmol/1 (17 +/- 25 vs. 25 +/- 31 days; P = 0.0991). The cases with severe
      ketoacidosis, compared to those with mild ketoacidosis (blood pH 7.21 - 7.34)
      showed shorter period of symptoms too (P = 0.0658). Moderate positive relation
      existed between the age at diagnosis and duration of symptoms (chi 2 = 43.28,
      D.F. = 8, P = 0.0000). The percentage of severe ketoacidosis is higher in the
      younger age groups. Febrile illness, preceding the start of the symptoms was more
      common in the groups with shorter duration of symptoms (up to 1 month), but did
      not change the proportion of severe ketoacidosis. No significant difference was
      found between the level of mother's education and duration of the symptoms before
      diagnosis (P = 0.9782). We conclude that the level of metabolic disturbances at
      the diagnosis of IDDM among children was not influenced by the duration of the
      preceding symptoms. The severity of clinical picture was possibly dependent on
      the degree of insulinopenia, i.e. the rate of beta-cell destruction. Clinical
      heterogeneity was possibly dependent on genetical heterogeneity related to HLA
      class II genes.

PMID- 9015687
TI  - Why does diabetic autonomic neuropathy predict IDDM mortality? An analysis from
      the Pittsburgh Epidemiology of Diabetes Complications Study.
AB  - BACKGROUND: Previous studies have suggested that IDDM subjects with diabetic
      autonomic neuropathy (DAN) have a greatly increased risk of mortality which may
      relate to a specific cardiologic etiology. OBJECTIVES: To examine the predictors
      of DAN in IDDM and its relationship to subsequent mortality. STUDY POPULATION:
      The Epidemiology of Diabetes Complications Study based on an incident cohort of
      childhood onset IDDM subjects. Data from two examinations, separated by 2 years,
      are utilized. METHODS: Diabetic autonomic neuropathy was determined by
      Expiration/Inspiration (E/I ratio). A variety of baseline risk factors were
      related to its subsequent incidence (n = 57 out of 325 subjects free of DAN at
      baseline). Two-year mortality by DAN status was also determined for all 479
      subjects seen at baseline. RESULTS: Duration of diabetes, the cardiovascular risk
      profile (hypertension, elevated LDL cholesterol and triglycerides), and other
      complications (e.g. nephropathy) were all univariately associated with subsequent
      DAN (P < 0.01). Smoking status and hemoglobin A1 (HbA1) but less strongly,
      related (P < 0.05). Cox proportional hazards modeling showed diabetes duration
      and HbA1 to be significant independent predictors. Distal Symmetrical
      Polyneuropathy also contributed if added to the model. Mortality was increased
      four-fold in those with DAN (P = 0.005), although this difference no longer was
      significant after adjustment for baseline nephropathy (P = 0.35) or hypertension
      (P = 0.42). CONCLUSIONS: Duration of diabetes and HbA1 are the major predictors
      of DAN. However, although DAN is clearly associated with increased mortality,
      this is largely explained by associations with complications (e.g. nephropathy)
      and increased cardiovascular risk factors (e.g. hypertension).

PMID- 9015688
TI  - Patterns of hospital use, family history and co-existing conditions among urban
      African-American and Hispanic-American children with insulin-dependent diabetes
      mellitus.
AB  - Little information is available about insulin-dependent diabetes mellitus (IDDM)
      when it occurs among US minorities. The incidence of IDDM among African-American
      and Hispanic children < 18 years of age was determined in the city of Chicago.
      Hospital records were used as the primary source of cases, and a small amount of
      additional data was collected from the medical charts. Cases were drawn from
      records at 37 hospitals in Cook County, IL. African-American and Hispanic
      patients using insulin, residing in the city of Chicago, and < 18-years-old at
      onset were registered. Three secondary sources were used and overall
      ascertainment was estimated at 86%. There were 413 new cases during the 6-year
      interval 1985 through 1990. The age-standardized incidence of IDDM was
      13.2/100,000 (95% confidence interval (C.I.) 11.8-14.8) among African-Americans
      and 10.8/100,000 (95% C.I. 9.5-12.3) among Hispanics. Hospital use differed
      between African-Americans and Hispanics, presumably based on geographic, cultural
      and financial factors. Diabetes among the first degree relatives of children from
      both ethnic groups was common, and the most frequently listed co-morbid
      conditions were asthma and obesity. The risk for IDDM in Chicago is among the
      highest for both African-origin and Hispanic children worldwide. The prevalence
      of asthma and obesity parallels the high prevalence of these conditions among non
      diabetic children in Chicago. The ongoing epidemic of non-insulin-dependent
      diabetes mellitus (NIDDM) among African-Americans and US Hispanics is likely to
      be the reason for the large number of minority IDDM patients who have a first
      degree relative with diabetes.

PMID- 9015689
TI  - Prevention of IDDM: a public health perspective.
AB  - Insulin dependent diabetes mellitus (IDDM) poses a large social and economic
      burden on society. There are now methods for identifying persons at risk for IDDM
      and increasing evidence suggest that it may be possible to delay or even prevent
      the clinical presentation of the disease. This raises the question of whether a
      prevention program for IDDM should be initiated through public health channels.
      Review of the literature suggests that in spite of the considerable societal
      burden associated with diabetes, there are currently no broadly applicable,
      effective methods for identifying persons at increased risk of developing IDDM
      nor are there proven strategies for its prevention when risk is established.
      Until strategies to identify persons at risk of IDDM and methods to prevent the
      onset of disease are established, a better use of limited resources may be the
      secondary and tertiary prevention of complications of the disease.

PMID- 9015690
TI  - Transcutaneous and arterial carbon dioxide tension at various conditions of fetal
      stress in lambs.
AB  - In an acute fetal lamb model the relation between arterial PCO2 (PaCO2),
      transcutaneous PCO2 (tcPCO2) and pH was studied at different conditions of
      stress. Occlusion of the maternal common iliac artery for 8 min, umbilical cord
      obstruction for 5 min and placental embolization were performed subsequently,
      every time with an interval of 1 h for fetal recuperation. During the first 2
      experiments arterial values changed rapidly after occlusion and returned nearly
      to normal within 30-60 min after the end of occlusion. TcPCO2 started to increase
      several minutes after occlusion and reached its maximum about 5 min after the end
      of occlusion. Afterwards a gradual decrease towards the onset value was observed.
      During placental embolization tcPCO2 did not increase until 15 min before fetal
      death. It is concluded that tcPCO2 can follow a gradual trend, but not quick
      changes in PaCO2.

PMID- 9015691
TI  - Comparative effect of the calcium antagonist verapamil and the synthetic steroids
      gestrinone and danazol on human monocyte phagocytosis in vitro.
AB  - Recent evidence suggested that periovulatory treatment with an immunomodulatory
      agent such as verapamil might be an effective alternative to conventional
      treatment for endometriosis-associated subfertility. In particular, it has been
      reported that the drug might reduce the accentuated macrophage peritoneal
      activation demonstrated in patients with endometriosis. In this study, we
      compared the effect of the calcium antagonist verapamil with those of gestrinone,
      danazol and testosterone on human monocyte phagocytosis in an attempt to evaluate
      any significant differences in their ability to influence a parameter of cell
      inflammatory activation. Peripheral blood monocytes were isolated from 37 healthy
      women. Monocyte function was determined by phagocytosis of fluorescent
      microspheres after an overnight incubation in the presence or absence of the
      various agents. This study indicates that verapamil at the pharmacological
      concentration of 0.4 micrograms/ml, the systemic level in patients taking 40-80
      mg/8 h p.o., significantly inhibits monocyte function. A lower immunosuppressive
      but still significant effect was achieved in this assay system with gestrinone at
      a concentration of 3 x 10(-8) M). The pharmacological concentration of danazol
      (10(-6) M) and the physiologic concentration of testosterone (10(-8) M) did not
      significantly affect this immunologic test system. These results provide evidence
      that verapamil is able to exert a slightly greater immunosuppressive effect than
      steroidal drugs on monocyte phagocytosis. However, due to the small differences
      observed, further studies on the biological mechanism of the drug seem to be
      necessary to completely elucidate its potential role in endometriosis-associated
      subfertility.

PMID- 9015692
TI  - Intraplacental spectral Doppler scanning: fetal growth classification based on
      Doppler velocimetry.
AB  - The purpose of the study was to develop a Doppler modality for effective
      assessment of the fetoplacental circulation. Calculations based upon a
      theoretical model were employed to predict downstream pulsatility values in the
      fetoplacental circulation. The clinical study included 83 pregnancies between 32
      and 36 weeks of gestation. Sixty-nine women were recruited from our low-risk
      clinic and had uncomplicated pregnancies. Fourteen patients had complications
      suspected to be associated with placental pathology. All 83 patients demonstrated
      UA Doppler indices within the normal limits for the gestational age. The study
      induced intraplacental and UA Doppler waveform analyses. The ratios between
      intraplacental and UA PI values (at the cord insertion to the placenta) were
      calculated. Nineteen patients with intraplacental to UA (placental cord
      insertion) PI ratios > 1 (abnormal) had adverse pregnancy outcome. The study
      demonstrates the importance of detailed scanning of the intraplacental pulsatile
      waveforms and the importance of using the ratio between the intraplacental and UA
      Doppler indices as an additional method for evaluation of the fetoplacental
      circulation. The method might be proven more effective mainly in the early stages
      of placental disease when a relatively small number of the placental terminal
      arterioles are affected with a negligible effect on the UA Doppler indices, and
      also in the evaluation of the large placenta. A fetal growth classification based
      on detailed intraplacental velocimetry and cord to intraplacental flow gradient
      is proposed.

PMID- 9015693
TI  - Fetal weight estimation by symphysis-fundus height and gestational age.
AB  - A new method for estimating the fetal weight is described, based on symphysis
      fundus height and gestational age. The relationship between ultrasound-estimated
      fetal weight, gestational age, and symphysis-fundus height was determined using
      multiple regression analysis in a low-risk group. The accuracy of the regression
      formula was tested retrospectively on two target populations: a second low-risk
      group and a higher risk group undergoing elective delivery. The formula
      overestimated weight by 3.6%. The standard deviation of the random errors for the
      first group was 10.3% whereas in the second it was 11.9%. Fetal weight estimation
      using symphysis-fundus height and gestational age can be performed with an
      accuracy comparable to that of ultrasound.

PMID- 9015694
TI  - Assessment of fetal well-being in methadone-maintained pregnancies: abnormal
      nonstress tests.
AB  - OBJECTIVE: To investigate parameters of fetal well-being (characteristics of
      nonstress test, NST, and antepartum fetal heart rate, FHR, patterns) and selected
      neonatal outcomes in pregnant women on methadone maintenance. STUDY DESIGN: A
      matched case-control study of methadone-treated women receiving prenatal and
      intrapartum care at a Bronx municipal hospital during 1992-1994. 102 NSTs
      obtained from 24 methadone-treated women after 35 weeks of pregnancy were
      compared to 96 NSTs from a control group (n = 24), matched for maternal age,
      parity, and gestational age. All NSTs were evaluated for general characteristics
      including time interval between initiation and achievement of reactive NST (2
      accelerations > or = 15 bpm lasting for at least 15 s in a 20-min period),
      baseline, amplitude of fluctuation, frequency of fluctuation, accelerations and
      decelerations. The scoring system described by Lyons et al. was used for all
      NSTs. All nonreactive NSTs were followed with biophysical profile tests. RESULTS:
      The frequency of nonreactive NSTs was significantly higher for methadone
      maintained women compared to controls (19.6 vs. 4.2%; p < 0.01). The average
      length of time to achieve reactive NST was significantly (p = 0.0016) longer for
      the methadone-treated group when compared to controls (35.50 +/- 20.96 vs. 14.85
      +/- 9.03 min). The total score (Lyons et al.) was significantly lower (p <
      0.0007) for the methadone-treated group compared to controls. Mean birth weight,
      Apgar scores at 1 and 5 min, meconium, and umbilical cord artery pH were not
      significantly different for methadone-exposed neonates compared to controls.
      CONCLUSION: Methadone-maintained pregnancies are significantly associated with a
      higher incidence of nonreactive NSTs, longer intervals to achieve reactive NSTs
      and lower NST scores compared to controls. This may reflect an altered response
      in fetal central nervous system neurotransmitters and changes in fetal behavior
      induced by methadone.

PMID- 9015695
TI  - Thrombin-antithrombin III complexes and antithrombin III in amniotic fluid.
AB  - We measured thrombin-antithrombin III (TAT) complexes and antithrombin III (AT
      III) in amniotic fluid and blood plasma of 39 parturient women. TAT was measured
      by ELISA. Partigen plates were used for measuring the antigen of AT III, and
      activity was determined using chromogenic substrate. While AT III activity and AT
      III antigen were below 20% of plasma values, TAT concentration was 2-4 times
      higher in amniotic fluid than in blood plasma (over twice at the onset of labour,
      i.e. 54.2 +/- 26.4 and 20.7 +/- 10.7 ng/ml, and approximately 4 times after
      childbirth, i.e. 108.9 +/- 49.2 ng/ml in amniotic fluid and 27.8 +/- 13.2 ng/ml
      in blood plasma, respectively). We have concluded that thrombin generation and
      TAT formation in amniotic fluid are are of significantly higher intensity than in
      plasma, and they increase during labour.

PMID- 9015696
TI  - Progesterone levels in preterm labor are not affected by ritodrin treatment.
AB  - Several in vitro studies reported on increased levels of progesterone secretion
      from placental tissue. This was not tested in vivo. To study the issue we
      examined progesterone levels in women presenting with premature labor before
      treatment, and 24 h and 48 h after beginning ritodrin treatment. A control group
      consisted of women treated with indomethacin for preterm labor. There were 13
      women in the ritodrin group and 12 in the control group. The mean concentration
      of progesterone in the ritodrin group was 161.7 +/- 74.2, 132 +/- 50.2 and 145 +/
      49.8 ng/ml before treatment, and 24 and 48 h after ritodrin treatment,
      respectively. The mean progesterone concentration of the group treated with
      indomethacin was 129 +/- 45.6, 132 +/- 49.5 and 138.6 +/- 53.5 ng/ml before
      treatment, and 24 and 48 h after treatment, respectively. There were no
      statistically significant differences between the groups or within each group
      before and after treatment. Ritodrin treatment does not affect progesterone
      levels in vivo as demonstrated by in vitro studies.

PMID- 9015697
TI  - Serum level of endothelin-1 and -2 in pregnancies complicated by EPH gestosis.
AB  - We examined the endothelin (ET)-1 and -2 concentration in peripheral blood serum
      of 27 pregnant patients with EPH gestosis who underwent cesarean section between
      the 32nd and 38th week of gestation (group Gc). The control group consisted of 26
      healthy pregnant women who underwent cesarean section due to fetal malpositions
      (group Kc). ET concentration in umbilical venous blood serum in 22 cases of EPH
      gestosis (group Gp) and 20 cases from the control group (Kp) was measured after
      delivery. ET concentration was determined with use of a radioimmunoassay method
      after extraction with column chromatography. The mean ET concentration was 41.55
      pg/ml in group Gc and was significantly higher than in group Kc-6.77 pg/ml. The
      mean ET concentration in umbilical blood serum in group Gp was 50.59 pg/ml and
      was significantly higher than in Gc and Kp groups-where ET concentration was
      17.11 pg/ml. These studies indicate that the high level of ET may play an
      important role in pathogenesis of EPH gestosis as well as having influence on
      uteroplacental and umbilicoplacental circulation.

PMID- 9015698
TI  - Hormonal patterns in postmenopausal women during gynecological surgery.
AB  - The endocrine effects of surgical trauma are incompletely understood. We have
      measured serum levels of cortisol, 17 alpha-hydroxyprogesterone (17-OHP),
      dehydroepiandrosterone (DHA), 4-androstene-3,17-dione (A4) and total (free +
      conjugated) estrone (tE1) before, during and up to 6 days after surgery in 30
      postmenopausal women undergoing repair of vaginal prolapse. Anesthetic procedures
      were standardized. During surgery and the early postoperative hours the serum
      steroid pattern closely resembled that found during a diagnostic ACTH challenge
      test with a simultaneous increase in all adrenocortical steroids, while tE1
      levels were unchanged. During the late postoperative period the levels of
      cortisol, 17-OHP and A4 were still elevated up to 24 h after surgery while the
      levels of DHA were normal or even decreased. The postoperative pattern of
      adrenocortical steroids may reflect a redistribution of the intra-adrenal steroid
      flux in favor of cortisol production. The tE1 levels were elevated in the early
      and, most pronounced, in the late postoperative phase. tE1 was positively
      correlated to A4, in the early but not in the late postoperative phase. The late
      increase in tE1 probably reflects an impaired bowel function in connection with
      surgery, leading to increased reabsorption during enterohepatic circulation.

PMID- 9015699
TI  - Serum levels of androstenedione, testosterone and dehydroepiandrosterone sulfate
      in patients with premature ovarian failure to age-matched menstruating controls.
AB  - Serum concentrations of androstenedione, testosterone and dehydroepiandrosterone
      sulfate (DHEAS) were measured in 29 patients with premature ovarian failure (POF)
      and an identical number of age-matched normal control subjects. The study was
      aimed at determining possible differences in androgen concentrations of ovarian
      and adrenal origin in POF patients and age-matched normal menstruating controls.
      Serum testosterone and DHEAS concentrations in the 2 populations were not
      significantly different. The serum androstenedione concentration in the POF
      patient group (3,077.50 +/- 1,122.33 pmol/l) was significantly lower than in age
      matched normal control subjects (4,167.70 +/- 1,381.09 pmol/l, p < 0.005),
      possibly reflecting the loss of ovarian androstenedione secretion and/or a subtle
      defect in adrenal steroidogenic capacity.

PMID- 9015700
TI  - Gynecological symptoms and vaginal wet smear findings in women with cervical
      human papillomavirus infection.
AB  - OBJECTIVES: To investigate the signs, symptoms and changes in the vaginal milieu
      that could be associated with cervical human papillomavirus infection (CHPI).
      STUDY DESIGN: Women (n = 972) attending for contraceptive advice were tested for
      human papillomavirus in cervical samples. Results of gynecological history,
      examination, and vaginal wet smear findings were compared between CHPI patients
      and negative women. RESULTS: Sixty-six (6.8%) of the women had a CHPI. Bacterial
      vaginosis was more common among those with, than without, CHPI, but the
      significance of this association was abolished after adjustment for age and for
      markers of sexual risk-taking. Vaginal discharge with a fishy odor, a positive
      amine test, and genital fissures showed significant correlations with CHPI, which
      persisted after adjustments. Symptoms of proctitis also correlated with CHPI, and
      remained significant after adjustment for anal sex. CONCLUSION: Bacterial
      vaginosis is associated with the presence of CHPI, possibly due to sexual
      behavioral factors. However, several other features, in particular the presence
      of amines, may be independently associated with CHPI.

PMID- 9015701
TI  - Reoperation rates for recurrent ovarian endometriomas after surgical excision.
AB  - This was a retrospective study analyzing the need for reoperation for recurrent
      endometriomas after surgical therapy. There were 104 women who were followed
      after surgical excision of endometriomas, with a cross section of 46 gynecologic
      surgeons. When using a life-table for follow-up analysis, only 2.9% of all
      patients had reoperation for recurrence, with a maximum recurrence probability of
      7% at 32 months of follow-up.

PMID- 9015702
TI  - The effect of uterine volume on uterine artery Doppler velocimetry in the
      myomatous state.
AB  - This study aimed at testing the hypothesis that lower uterine arterial (UA)
      Doppler indices are caused by increased uterine volume rather than the presence
      of myoma. Uterine volumes were calculated and uterine and/or myomal arterial
      pulsatility index (PI) and resistance index (RI) were obtained by transvaginal
      color Doppler ultrasonography. The mean uterine volume in the myomatous group
      (276.2 cm3; range 65-928 cm3, n = 100) was significantly greater than that of the
      control group (101.4 cm3; range 36-171 cm3; n = 60; p = 0.00). The mean UA PI and
      RI values in the study group were significantly lower than their corresponding
      values in the control group (0.77 +/- 0.08 and 1.69 +/- 0.47 vs. 0.82 +/- 0.06
      and 1.97 +/- 0.49, respectively, p = 0.01). When the myomatous uterine volumes of
      the study group were categorized into two subgroups (< 200 and > or = 200 cm2)
      the UA PI and RI values were lower in the latter group (p = 0.006 and p = 0.015,
      respectively). However, after analysis of receiver-operator-characteristic
      curves, none of the UA Doppler indices could differentiate the myomatous uterus
      from the normal uterus.

PMID- 9015703
TI  - Different coexisting endometrial histological features in asymptomatic
      postmenopausal breast cancer patients treated with tamoxifen.
AB  - In an attempt to assess the hypothesis that different endometrial sites may
      respond differently to tamoxifen exposure in postmenopausal women, hysteroscopic
      selected endometrial histology was investigated in 175 postmenopausal breast
      cancer patients who received continuous treatment with tamoxifen, and in 27
      similar patients not treated with tamoxifen who served as controls. In the
      tamoxifen-treated patients 14 (8.0%) developed endometrial polyps. Of 14
      patients, 8 (57.2%) each displayed atrophic endometrium in the same histologic
      specimen, 5 (35.7%) each had coexisting simple hyperplasia, and 1 (7.1%) other
      had complex hyperplasia. Another 21 (12.0%) developed simple or complex
      hyperplasia. The endometrial hyperplasia coexisted with atrophic endometrium in
      all these patients. All these lesions were selectively identified by
      hysteroscopic examination prior to the endometrial biopsy. In the control group 3
      (11.0%) had simple hyperplasia and 2 (7.4%) had endometrial polyps. The above
      results support the hypothesis that the endometrium of postmenopausal breast
      cancer patients on tamoxifen treatment may possess different responses to
      tamoxifen exposure.

PMID- 9015704
TI  - Umbilical venous pulsation associated with hypercoiled cord in growth-retarded
      fetuses.
AB  - Venous pulsatile flows were detected by pulsed Doppler flow velocimetry
      throughout the entire umbilical cord in 2 cases of intrauterine growth
      retardation. Although the hearts of these fetuses had no anomalies and their
      inferior vena cava flows had normal flow velocity patterns, their cords were
      severely coiled. In these cases, the pulsatile flow in the umbilical cord vein
      was caused not by an increase in the preload of the fetal heart, but only by
      hypercoiling of the umbilical cord. This phenomenon also suggests that the coiled
      umbilical cord exerts a pump-like effect known as a 'pulsometer'.

PMID- 9015705
TI  - Malignant struma ovarii. A case report and review of the literature.
AB  - Malignant struma ovarii is a rare form of ovarian carcinoma; only 3 cases of its
      pure papillary type have been reported in the literature. A new case of malignant
      papillary struma ovarii arising in an asymptomatic 32-year-old woman is
      presented. Due to its rarity, there has been confusion in the diagnosis and
      management of malignant struma ovarii. Criteria for the diagnosis of malignant
      papillary struma ovarii are proposed. Conservative treatment after a complete
      staging procedure is possible due to the usually benign course and low incidence
      of metastases of this tumor.

PMID- 9015707
TI  - Immunohistochemical localization of transforming growth factor-beta 1 beta 2
      during folliculogenesis in the quail ovary.
AB  - Immunohistochemical methods were used to show the presence and distribution of
      transforming growth factor-beta 1 and beta 2 during folliculogenesis in quail
      ovarian tissues. The results indicated that both transforming growth factor-beta
      subtypes are present. Immunolabelling for transforming growth factor-beta 1
      demonstrated that prelampbrush oocytes are immunoreactive in the Balbiani
      complex, and developing and pre-ovulatory oocytes in the zona radiata.
      Immunolabelling was also associated with granulosa cells. The number of stained
      granulosa cells decreased during folliculogenesis. In the pre-ovulatory
      follicles, immunolabelling was found predominantly in the theca interna.
      Immunolabelling for transforming growth factor-beta 2 was associated with the
      zona radiata of developing and pre-ovulatory follicles, and with stromal
      interstitial cells. Moderate immunoreactivity was found in the Balbiani complex
      of prelampbrush oocytes. Weak immunolabelling was localized in the granulosa
      cells of prelampbrush follicles, and in a few cells of the theca interna of pre
      ovulatory follicles. The immunolocalization of transforming growth factor-beta 1
      and -beta 2 in the quail ovary supports their autocrine and/or paracrine role in
      avian ovarian processes.

PMID- 9015708
TI  - Lack of chondroitin sulphate epitope in the proliferating zone of the growth
      plate of chicken tibia.
AB  - Monoclonal antibodies specific to chondroitin sulphate (CS-56) and keratan
      sulphate (AH12) were used to localize proteoglycans in the proximal tibial
      articular cartilage and growth plate of broiler chickens. There was no CS-56
      labelling in the proliferative zone of the growth plate. In contrast, intense
      labelling with this antibody was observed in the transitional and hypertrophic
      zones of the growth plate and the articular cartilage. This was confirmed by
      extracting chondroitin sulphate fractions from different zones of the growth
      plate and articular cartilage, and examining their antigenicities to CS-56 by
      ELISA inhibition assay. It was suggested that the maturation of chondrocytes in
      the growth plate is related to the production of chondroitin sulphate with CS-56
      epitope, which may be a prerequisite for normal endochondral bone formation in
      the chicken tibia. The role of chondroitin sulphate recognized by CS-56 in the
      articular cartilage is unknown.

PMID- 9015709
TI  - Keratin antigen retrieval in oral mucosal biopsies using microwave processing.
AB  - In immunohistochemistry, it is well known that the majority of monoclonal
      antibodies to keratins work best on fresh frozen tissue specimens, yet in
      clinical practice most biopsies are routinely fixed in formaldehyde. This
      seriously limits the range of keratins that can be reliably assessed in
      retrospective studies (particularly where only rare archival material exists) and
      where subtle changes during tissue differentiation may be important. Antigen
      retrieval using exposure to microwave radiation is one technique that has been
      applied successfully to other tumour markers (e.g., p53). However, few papers
      have used this method when immunolabelling for keratins, in spite of the
      widespread use of antikeratin antibodies as markers of differentiation. The
      effect of keratin antigen retrieval using microwave processing was assessed on a
      range of oral mucosal biopsies, since the oral cavity displays a wide range of
      keratins. A panel of six well characterized antibodies was chosen: LP34 (Ck1, 5,
      6, 18), LH1 (Ck10), LL025 (Ck16), A53 BA2 (Ck19), AE8 (Ck13), and E3 (Ck17). For
      each specimen, one piece was stored in liquid nitrogen and another piece fixed in
      formalin. Tissue sections were cut from each and, using the peroxidase avidin
      biotin technique, keratin expression was recorded for a frozen section, a dewaxed
      section, and a microwave-heated dewaxed section. Although overall there was a 25%
      improvement in identification of keratins after microwaving, some antibodies
      performed better than others. Given that keratins have been shown to be of value
      in tumour diagnosis, this study suggests that microwave processing of archival
      material can be a valuable adjunct to such analysis.

PMID- 9015710
TI  - The G-cells in the dog: a light and electron microscope immunocytochemical study.
AB  - An immunohistochemical study has been performed to analyse the distribution of
      gastrin cells in the gastrointestinal tract of the dog. This study revealed that
      G-cells immunoreactive for gastrin were almost exclusively present in the pyloric
      antral mucosa, mainly in the middle third of the pyloric mucosa. The calculated
      number of G-cells per surface unit area was 8.5 x 10(3)-1.2 x 10(4) cells cm-2.
      Some gastrin-immunopositive cells were found in the first 10 mm of the proximal
      duodenum, mainly in the villous region. The fundic area of the dog stomach, the
      oesophagus, small intestine, caecum, colon, rectum, salivary glands, liver and
      pancreas were all immunonegative for gastrin. At the ultrastructural level, three
      different types of granules (150-400 nm) were evident in G-cells: electron-dense,
      electron-lucent and intermediate forms. Most of them were located in the
      subnuclear region of the cell. The effect of fixation of the antral mucosa at
      different pH levels was studied. In samples fixed with acid solutions, most of
      the G-cell granules were of the electron-dense type and were strongly
      immunopositive for gastrin. Fixation of samples at a basic pH resulted in most of
      the gastrin granules losing their contents into the cytoplasm, and the positive
      reaction to gastrin was then located in the cytoplasm and at the periphery of the
      electron-lucent granules.

PMID- 9015736
TI  - Molecular pharmacology and pathophysiological significance of endothelin.
AB  - Since the discovery of the most potent vasoconstrictor peptide, endothelin, in
      1988, explosive investigations have rapidly clarified much of the basic
      pharmacological, biochemical and molecular biological features of endothelin,
      including the presence and structure of isopeptides and their genes (endothelin
      1, -2 and -3), regulation of gene expression, intracellular processing, specific
      endothelin converting enzyme (ECE), receptor subtypes (ETA and ETB),
      intracellular signal transduction following receptor activation, etc. ECE was
      recently cloned, and its structure was shown to be a single transmembrane protein
      with a short intracellular N-terminal and a long extracellular C-terminal that
      contains the catalytic domain and numerous N-glycosylation sites. In addition to
      acute contractile or secretory actions, endothelin has been shown to exert long
      term proliferative actions on many cell types. In this case, intracellular signal
      transduction appears to converge to activation of mitogen-activated protein
      kinase. As a recent dramatic advance, a number of non-peptide and orally active
      receptor antagonists have been developed. They, as well as current peptide
      antagonists, markedly accelerated the pace of investigations into the true
      pathophysiological roles of endogenous endothelin-1 in mature animals; e.g.,
      hypertension, pulmonary hypertension, acute renal failure, cerebral vasospasm,
      vascular thickening, cardiac hypertrophy, chronic heart failure, etc. Thus, the
      interference with the endothelin pathway by either ECE-inhibition or receptor
      blockade may provide an exciting prospect for the development of novel
      therapeutic drugs.

PMID- 9015711
TI  - Tissue distribution and immunohistochemical localization of the collagen-binding
      heat-shock protein gp46 in neonatal rats.
AB  - Collagen-binding heat-shock proteins of M(r) 46-47 kDa have been postulated to
      function as putative molecular chaperones in the biosynthesis of collagen in
      several species. The rat homologue of this family of heat-shock proteins is
      called gp46. In the present study, we employed Western blotting and
      immunohistochemical methods to determine the tissue distribution and cellular
      localization of gp46 in the thoracic aorta, heart, kidney, liver and lung of
      eight-day-old Wistar rats. Highest levels of gp46 were detected in the thoracic
      aorta and lung, followed by the kidney and heart. Gp46 levels were low to
      undetectable by Western blot analysis in the liver. Immunohistochemistry revealed
      that gp46 labelling was observed almost exclusively in three distinct cell types:
      fibroblasts, muscle cells, and some epithelial cells. Gp46 was detected in the
      fibroblasts of the hepatic triad, in the interstitium of the alveolar wall and in
      the tunica adventitia of blood vessels in the majority of tissues examined, in
      atrial and ventricular cardiomyocytes, in vascular smooth muscle cells of the
      abluminal portion of the tunica media, in parietal epithelial cells and mesangial
      cells of the glomerulus, in epithelial cells of the distal tubules and collecting
      ducts in the kidney and clusters of immature renal tubules, in epithelial cells
      of the bile duct, and in mesodermal cells surrounding the liver. These results
      demonstrate that gp46 is present in collagen producing cells and cells undergoing
      rapid growth and development, suggesting that gp46 may play a significant role in
      these processes.

PMID- 9015706
TI  - Articular cartilage destruction in experimental inflammatory arthritis: insulin
      like growth factor-1 regulation of proteoglycan metabolism in chondrocytes.
AB  - Rheumatoid arthritis, a disease of unknown aetiology, is characterized by joint
      inflammation and, in its later stages, cartilage destruction. Inflammatory
      mediators may exert not only suppression of matrix synthesis but also cartilage
      degradation, which eventually leads to severe cartilage depletion. Systemically
      and locally produced growth factors and hormones regulate cartilage metabolism.
      Alterations in levels of these factors or in their activity can influence the
      pathogenesis of articular cartilage destruction in arthritic joints. The main
      topic of the present review is the role of the anabolic factor insulin-like
      growth factor-1 in the regulation of chondrocyte metabolic functions in normal
      and in diseased cartilage. This is the most important growth factor that balances
      chondrocytes proteoglycan synthesis and catabolism to maintain a functional
      cartilage matrix. A brief overview of how chondrocytes keep the cartilage matrix
      intact, and how catabolic and anabolic factors are thought to be involved in
      pathological cartilage destruction precedes the review of the role of this growth
      factor in proteoglycan metabolism in cartilage.

PMID- 9015737
TI  - Efonidipine, a long-acting dihydropyridine derivative, attenuates coronary
      vasoconstriction induced by endothelin-1 in dogs.
AB  - Effect of efonidipine, a long-acting dihydropyridine derivative, on the
      endothelin-1 (ET-1)-induced coronary vasoconstriction was studied in open-chest
      anesthetized dogs. Efonidipine (0.03 or 0.1 mg/kg) was administered i.v. 10 min
      before an intracoronary injection of ET-1 (30 pmol/kg). An intracoronary
      injection of ET-1 decreased coronary blood flow (CBF) that was measured by a flow
      probe. The ET-1-induced decrease in CBF was sustained for more than 30 min
      without significant changes in blood pressure and heart rate. Pretreatment with
      efonidipine attenuated the decrease in CBF induced by ET-1 significantly and dose
      dependently. ET-1 also reduced coronary diameter for more than 30 min as
      evaluated by the coronary angiography technique. Pretreatment with efonidipine
      also attenuated the reduction in coronary diameter induced by ET-1 significantly
      and dose-dependently. These effects of efonidipine were sustained for at least 30
      min after the ET-1 administration. It is concluded that efonidipine attenuates
      the ET-1-induced vasoconstriction, and therefore the drug would be useful for
      some patients with variant angina, in which ET-1 is involved in the genesis of
      coronary vasoconstriction.

PMID- 9015738
TI  - Menadione toxicity in cultured rat cortical astrocytes.
AB  - We examined the effect of menadione on the morphology and viability of cultured
      astrocytes. Exposure of astrocytes to menadione induced a progressive cell death.
      The toxic effect of menadione was concentration- and time-dependent. Menadione
      toxicity was blocked by antioxidants, superoxide dismutase, catalase and iron
      chelators, indicating that superoxide anions (O2-), hydrogen peroxide (H2O2) and
      hydroxyl radicals (.OH) are all involved in menadione toxicity. Menadione
      cytotoxicity should be useful as a model for studying the mechanisms underlying
      oxidative injury in the brain and for the screening of drugs that may attenuate
      cell damage caused by oxidative stress.

PMID- 9015739
TI  - Inositol 1,4,5-trisphosphate- and caffeine-sensitive Ca(2+)-storing organelle in
      bovine adrenal chromaffin cells.
AB  - The uptake and release properties of Ca2+ by several subcellular fractions of the
      bovine adrenal medulla were investigated. Investigation by the 45Ca2+ tracer
      method showed that permeabilized cells and the fractions of mitochondria (MT) and
      microsomes (MC) caused ATP-dependent Ca2+ uptake in a Ca2+ concentration
      dependent manner (pCa 8-4), whereas permeabilized cells and the fractions of
      secretory granules (SG) were able to accumulate a significant amount of Ca2+ even
      in the absence of ATP, which was completed by the addition of hexokinase and
      glucose. In these organelle fractions, Ca2+ uptake in the presence of ATP at pCa
      7 and pCa 5.8 was well-correlated with the activity of the NADPH cytochrome c
      reductase (marker enzyme for the endoplasmic reticulum) and cytochrome c oxidase
      (marker enzyme for mitochondria), respectively. As detected by Fura-2 ratiometry,
      both inositol 1,4,5-trisphosphate (IP3) and caffeine caused concentration
      dependent Ca2+ releases from permeabilized cells and MC, but not from MT and SG.
      In an ATP-depleted condition, homogenates still took up a significant amount of
      Ca2+ but was not able to respond to IP3 and caffeine. These results suggest that
      the endoplasmic reticulum is a major Ca(2+)-storing organelle, which releases
      Ca2+ in response to IP3 and caffeine in bovine adrenal chromaffin cells.

PMID- 9015740
TI  - Effects of tri-, di- and monobutyltin on synaptic parameters of the cholinergic
      system in the cerebral cortex of mice.
AB  - Triorganotin compounds like tributyltin have been reported to be biodegraded to
      diorganotin, monoorganotin and then inorganic tin in animals after they have been
      ingested. Effects of tributyltin, dibutyltin and monobutyltin on various
      cholinergic parameters that are involved in synaptic transmission in the mouse
      cerebral cortex were investigated in vitro. Tributyltin and dibutyltin, but not
      monobutyltin, inhibited the activity of choline acetyltransferase, both the high
      affinity and low-affinity uptakes of choline into synaptosomes, and the binding
      of [3H]quinuclidinyl benzilate to muscarinic acetylcholine receptors. Tributyltin
      and dibutyltin, but not monobutyltin, had a slightly suppressive effect on the
      K(+)-induced release and synthesis of acetylcholine in slices of the cortex. All
      three butyltins at concentrations from 10(-6) to 10(-4) M had no effect on the
      activity of acetylcholinesterase. The extent of the inhibitory effects on the
      cholinergic parameters, apart from the activity of acetylcholinesterase, was
      slightly greater in the case of tributyltin than dibutyltin, in particularly at
      the highest concentration (10(-4) M) tested. Therefore, it is concluded that
      tributyltin metabolites inhibit various parameters of cholinergic activity with a
      potency ranking of tributyltin > dibutyltin > monobutyltin.

PMID- 9015741
TI  - Prolongation of the life span of cardiomyopathic hamster by the adrenergic beta 1
      selective partial agonist denopamine.
AB  - Influence of cardiotonic agents on the prognosis of heart failure depends on the
      individual therapeutic agents, and favorable and unfavorable effects of these
      agents have been reported in clinical trials. We studied the effect of the
      cardiotonic agent denopamine on the life span of cardiomyopathic hamsters (BIO
      14.6 strain) in the heart failure period. Non-treated hamsters started to die at
      40 weeks of age, and their survival rate decreased to 23.8% at the age of 65
      weeks. Hamsters treated with denopamine (400 ppm in diet) from 36 weeks of age
      did not die until the age of 52 weeks, except in cases of accidental death. The
      survival rate of this group at 65 weeks of age was about 40%. Survival rates of
      these 2 groups were significantly different (P < 0.05) when animals with
      accidental death were excluded. To elucidate the mechanism of the effect of
      denopamine, we performed several experiments after dietary treatment with
      denopamine for 4 to 6 weeks from 37 weeks of age. Denopamine treatment lowered
      plasma levels of noradrenaline and dopamine (P < 0.05), but affected neither the
      cardiac contractility nor the beta-adrenoceptor density. In summary, denopamine
      significantly decreases the mortality of cardiomyopathic hamsters. Its effect to
      lower the plasma catecholamine levels may be responsible for the beneficial
      effect of denopamine.

PMID- 9015742
TI  - Electrophysiological and pharmacological characteristics of ionotropic glutamate
      receptors in medial vestibular nucleus neurons: a whole cell patch clamp study in
      acutely dissociated neurons.
AB  - A patch clamp study was performed to determine which subtype of ionotropic
      glutamate receptors is involved in the glutamate-induced excitation of the medial
      vestibular nucleus (MVN) neurons. Whole cell recording was performed on MVN
      neurons that were acutely dissociated by enzymatic and mechanical treatments.
      Application of glutamate at a concentration of 100 microM produced a current with
      a reversal potential of approximately 0 mV. The glutamate-induced current was
      completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), a
      non-N-methyl-D-aspartate (NMDA)-receptor antagonist. Application of alpha-amino-3
      hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainic acid (KA), non-NMDA
      receptor agonists, at concentrations of 30 and 100 microM produced a
      concentration-dependent depolarization concomitantly with an increase in firing
      rates during current clamp recording. During voltage clamp recording, glutamate,
      AMPA and KA elicited a concentration-dependent current with an equilibrium
      potential of approximately 0 mV. To clarify whether NMDA receptors are present in
      MVN neurons, the effects of glycine on the glutamate- and NMDA-induced current
      were examined. Two types of NMDA receptor-mediated current (types 1 and 2) were
      obtained in terms of the difference in sensitivity to both magnesium ion and MK
      801, which act on the NMDA-receptor channel. In the type 1 neurons, the NMDA
      induced current was not apparently blocked by magnesium ion or MK-801, although a
      larger current was obtained in the absence of magnesium ion. In the type 2
      neurons, marked blockade of the NMDA-induced current was seen in the presence of
      magnesium ion and MK-801, as previously reported in other neurons of the central
      nervous system. These findings indicate the presence of both non-NMDA and NMDA
      receptors, which are involved in primary afferent transmission, in the MVN
      neuron, and two distinct types of NMDA receptors.

PMID- 9015743
TI  - Ouabain-induced cell proliferation in cultured rat astrocytes.
AB  - Ouabain markedly stimulated not only [3H]thymidine incorporation but also
      [3H]uridine incorporation into astrocytes. The effects were observed at 36-48 hr
      and 12-72 hr after addition of ouabain, respectively. The dose-response curves
      were both bell-shaped types with a peak at 10(-3) M for thymidine incorporation
      and 2 x 10(-3) M for uridine incorporation. Ouabain increased cell number as
      determined by an assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide and by a method using a hemocytometer. Low concentration of
      external K+ mimicked the effect of ouabain in stimulating [3H]-thymidine
      incorporation, and high concentration of external K+ blocked the effect of
      ouabain. In contrast to astrocytes, ouabain did not stimulate [3H]thymidine
      incorporation into C6 glioma and fibroblast cells. The effect of ouabain on
      [3H]thymidine incorporation in astrocytes was dependent on external Ca2+, and it
      was blocked by cycloheximide. These findings indicate that prolonged Na+, K(+)
      ATPase inhibition causes cell proliferation in cultured astrocytes in cell
      specific and Ca(2+)-dependent manners.

PMID- 9015744
TI  - New algorithms for real-time, 24 hr continuous and noise-adjusted power spectral
      analysis of heart rate and blood pressure fluctuations in conscious rats.
AB  - The effective combination of C+2 and assembler could realize real-time power
      spectral analysis of various fluctuation indexes simultaneously. The blood
      pressure (BP) waveform indexes (WIs) analyzed simultaneously were heart rate
      (HR), systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic
      blood pressure (DBP). Power amplitudes (very low frequency, VLFamp; low
      frequency, LFamp; and high frequency, HFamp) were evaluated by accurate BP
      waveform recognition, accurate automatic rejection of outliers, baseline
      adjustment in periodograms and digital filtering of each amplitude. In the in
      vivo experiments, the amplitudes were changed in a dose-dependent manner by
      methylatropine (HR-VLFamp, HR-LFamp and HR-HFamp), phentolamine (HR-LFamp, SBP
      VLFamp, SBP-LFamp and SBP-HFamp) and propranolol (HR-LFamp and SBP-LFamp). The
      absolute correlation coefficients of the amplitude and the change in each
      parameter were more than 0.96. In conclusion, this real-time, noise-adjusted
      power spectral analysis system for investigating HR and BP fluctuations enabled
      us to accurately evaluate autonomic nerve activity in conscious rats. Moreover,
      unlike other systems, this system was able to detect the biphasic changes in SBP
      HFamps caused by phentolamine.

PMID- 9015745
TI  - Antianginal effect of RS-5773, a diltiazem congener, in the methacholine-induced
      anginal model in rats.
AB  - The antianginal effect of RS-5773 ((2S,3S)-3-acetoxy-8-benzyl-2,3-dihydro-5-[2
      (dimethylamino)- ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one
      hydrochloride), a newly developed benzothiazepine derivative, was evaluated in an
      angina model rat. Close-coronary artery injections of methacholine in
      anesthetized rats evoked ischemic electrocardiographic (ECG) changes (S wave
      elevation of about 0.6 mV). The ECG changes produced by methacholine were
      reproducible for as long as 6 hr. Intravenous and intraduodenal administration of
      RS-5773, diltiazem or clentiazem produced dose-dependent suppressions of the
      ischemic ECG changes. RS-5773 exceeded the other two agents both in the maximum
      suppressive effect on S wave elevation and in the duration of action after
      intravenous administration. The antianginal potency expressed as AUC (area under
      the curve), i.e., the percent suppression of S wave elevation integrated over
      time, revealed that RS-5773 was 16 times and 7 times more potent than diltiazem
      and clentiazem, respectively. A similar order of potency difference was observed
      after intraduodenal administration, and RS-5773 sustained its effect for about 6
      hr at 3 mg/kg. In addition, RS-5773 did not cause excessive hypotension or
      depression of atrioventricular conduction. These results suggest that RS-5773 has
      a preferable profile as an antianginal agent.

PMID- 9015746
TI  - Effect of 5,6,7,8-tetrahydroneopterin on oxidative modification of low-density
      lipoprotein, and its uptake in the macrophage-like cell line J774.
AB  - Since oxidative modification of low-density lipoprotein (LDL) and uptake of the
      oxidized LDL by macrophages are closely related to the pathogenesis of
      atherosclerosis, we examined the inhibitory effect of 5,6,7,8-tetrahydroneopterin
      (NPH4) on Cu(II)-induced lipid peroxidation of LDL. NPH4 significantly inhibited
      both lipid peroxidation and the associated increase of electrophoretic mobility
      of ApoB protein. Furthermore, NPH4 suppressed the uptake of oxidized [14C]oleyl
      esterified LDL by the macrophage-like cell line J774. NPH4 may be a candidate for
      the treatment of atherosclerosis and other active oxygen-related diseases.

PMID- 9015747
TI  - Oxidative stress-induced increase in intracellular Ca2+ and Ca(2+)-induced
      increase in oxidative stress: an experimental model using dissociated rat brain
      neurons.
AB  - In order to study the oxidative stress-induced change in intracellular
      concentration of Ca2+ ([Ca2+]i) and Ca(2+)-induced oxidative stress, effects of
      hydrogen peroxide and ionomycin, a calcium ionophore, on rat cerebellar neurons
      were examined using a flow cytometer and fluorescent dyes: fluo-3 for monitoring
      [Ca2+]i; 2',7'-dichlorofluorescin, for reactive oxygen species; and 5
      chloromethylfluorescein, for cellular nonprotein thiols. Oxidative stress induced
      by hydrogen peroxide dose-dependently increased [Ca2+]i and decreased the content
      of nonprotein thiols. Ionomycin increased oxidative metabolism and decreased the
      content of nonprotein thiols. Results suggest that oxidative stress induces an
      increase in [Ca2+]i while an increase in [Ca2+]i increases oxidative stress in
      neurons.

PMID- 9015749
TI  - ICE processing and kinetic mechanism.
AB  - Interleukin-1 beta converting enzyme (ICE) has been the focus of major scientific
      efforts to discover pharmaceutically effective inhibitors. Little is known about
      the rates of the individual steps in catalysis. We report here that the rates of
      the two individual chemical steps in catalysis (acylation and deacylation) are
      each partially rate-limiting. This keeps the overall rate of the reaction less
      than 3% of the rate of the reaction for papain with its optimized substrate.
      Eight human ICE-like proteases have been published to date. They have levels of
      sequence identity that range from around 30% to greater than 50% throughout the
      full lengths of the proteins. This degree of relatedness increases when only the
      active domains are compared. This indicates that the greatest variability between
      family members occurs in their N-terminal prodomains. We propose several
      possibilities for the role for these prodomains in the regulation of enzyme
      processing.

PMID- 9015748
TI  - The interleukin-1 beta converting enzyme family of cysteine proteases.
AB  - Interleukin-1 beta converting enzyme (ICE) is the first enzyme of a new family of
      cysteine endoproteinases to be isolated and characterized. An overview of the
      structure and activity of ICE is outlined together with highlights of salient
      features common to members of each of the family members.

PMID- 9015750
TI  - In vitro and in vivo studies of ICE inhibitors.
AB  - Interleukin-1 beta-converting enzyme (ICE) is a cysteine protease responsible for
      proteolytic activation of the biologically inactive interleukin-1 beta precursor
      to the proinflammatory cytokine. ICE and homologous proteases also appear to
      mediate intracellular protein degradation during programmed cell death.
      Inhibition of ICE is a new antiinflammatory strategy being explored by the design
      of both reversible inhibitors and irreversible inactivators of the enzyme. Such
      compounds are capable of blocking release of interleukin-1 beta from human
      monocytes. ICE inhibitors that cross react against multiple ICE homologs can also
      block apoptosis in diverse cell types. ICE inhibitors impart protection in vivo
      from endotoxin-induced sepsis and collagen-induced polyarthritis in rodent
      models. Further optimization of the current generation of peptidyl ICE inhibitors
      will be required to produce agents suitable for administration in chronic
      inflammatory and neurodegenerative diseases.

PMID- 9015751
TI  - Characterization of mice deficient in interleukin-1 beta converting enzyme.
AB  - Interleukin-1 beta converting enzyme (ICE) processes the inactive prolL-1 beta to
      the proinflammatory mature IL-1 beta. ICE belongs to a family of cysteine
      proteases that have been implicated in apoptosis. To address the biological
      functions of ICE, we generated ICE-deficient mice through gene targeting
      technology. ICE-deficient mice developed normally, appeared healthy, and were
      fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis
      normally upon ATP treatment. Thymocytes from young ICE-deficient mice also
      underwent apoptosis when triggered by dexamethasone, gamma irradiation, or aging.
      ICE-deficient mice had a major defect in the production of mature IL-1 beta and
      had impaired IL-1 alpha production on LPS stimulation in vitro and in vivo. ICE
      deficient mice were resistant to LPS-induced endotoxic shock.

PMID- 9015752
TI  - Mammalian cell death proteases: a family of highly conserved aspartate specific
      cysteine proteases.
AB  - So far nine human aspartate-specific cysteine proteases (ASCPs) have been
      identified and cloned in our lab and others. Their sequence and structural
      homology to the nematode Ced-3 implicated them in the cell death pathway of
      mammalian cells. Recent evidence suggests that ASCPs initiate apoptosis by acting
      at or near the cell death effector level. However, it is not clear whether the
      activity of one or several of these enzymes is necessary for execution of
      apoptosis. In addition, it is not yet clear how the proenzymes of ASCPs are
      activated or what triggers their activation. Execution of apoptosis in higher
      eukaryotes is apparently more complicated than in nematodes. It is most likely
      that in mammalian cells this process involves the coordinated action of multiple
      ASCPs and multiple redundant proteolytic pathways.

PMID- 9015753
TI  - Proteases in Fas-mediated apoptosis.
AB  - Involvement of a unique family of cysteine proteases in the multistep apoptotic
      process has been documented. Cloning of several mammalian genes identifies some
      components of this cellular response. However, it is currently unclear which
      protease plays a role as a signal and/or effector of apoptosis. We summarize
      contributions to the data concerning proteases in Fas-mediated apoptosis.

PMID- 9015754
TI  - Macromolecular substrates for the ICE-like proteases during apoptosis.
AB  - The interleukin-1 beta-converting enzyme (ICE) family of proteases is an
      important component of the mechanism of the apoptotic process, but the
      physiologic roles of the different homologs during apoptosis remain unclear.
      Significant information about the roles of proteolysis in apoptosis will be
      gained through identification of the distal substrates through which these
      proteases achieve their pro-apoptotic effects. Identification of these substrates
      therefore remains an important challenge. A subset of autoantibodies from
      patients with systemic lupus erythematosus (SLE) recognize molecules that are
      specifically cleaved early during apoptosis. Several of the identified
      autoantigens are nuclear proteins (PARP, U1-70 kDa, and DNA-PKcs) that are
      substrates for CPP32 in vitro and in apoptotic cells. Of note, these substrates
      are catalytic proteins involved in homeostatic pathways, suggesting that
      abolition of homeostasis is one fundamental feature ensuring the rapid
      irreversibility of the apoptotic process. Identification of the other substrates
      for this protease family will provide the tools to assess the roles of the
      different proteases in apoptotic death.

PMID- 9015755
TI  - Calpain II expression is increased by changes in mechanical loading of muscle in
      vivo.
AB  - In the present investigation, we have tested the hypothesis that calpain
      expression or activity in skeletal muscle is influenced by changes in mechanical
      loading in vivo. Muscle unloading for 10 days produced no change in the
      concentrations of calpain I, or II, and no change in calpain activation, as
      assessed by measurements of the proportion of calpain I or II isoforms that
      exhibited autoproteolytic modifications. However, muscle reloading for 2 days
      produced a 90% increase in calpain II concentration per unit wet weight of muscle
      relative to ambulatory controls. Although no change in the activation index for
      calpain I or II was identified for reloaded muscle, this index is an expression
      of the proportion of the total mass of each calpain isoform that is
      autoproteolyzed. Thus, there is also approximately a 90% increase in autolyzed
      calpain II in muscle experiencing increased loading than in controls. Northern
      analysis shows that the concentration of mRNA for calpain II is increased in
      reloaded muscle, but no change in calpain II mRNA concentration in unloaded
      muscle. In situ reverse transcription polymerase chain reaction was used to
      confirm that nearly all calpain II mRNA in reloaded muscle is located in muscle
      fibers, with very little detectable calpain II mRNA in non-muscle cells present
      in the tissue. Together, these findings show that increased muscle loading causes
      a selective increase in the expression of calpain II isoform, thereby indicating
      that its regulation is independent from other calpain isoforms.

PMID- 9015756
TI  - Transient expression of M-CSF is important for osteoclast-like cell
      differentiation in a monocytic leukemia cell line.
AB  - Cells of U937, a human monocytic leukemia cell line, differentiate into
      macrophages by treatment with 12-o-tetradecanoylphorbol-13-acetate (TPA), whereas
      cells treated with 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3] continue to
      grow without undergoing differentiation. When U937 cells were successively
      treated with TPA and 1,25-(OH)2D3, tartrate-resistant acid phosphatase-positive
      multinucleated cells appeared at 5 days after the treatment. These osteoclast
      like cells released a soluble form of 45Ca from 45Ca-labeled bone particles.
      These cells were not formed when the order of treatment with TPA and 1,25-(OH)2D3
      was reversed. Use of either dexamethasone or interferon-gamma (IFN-gamma) was
      effective in inhibiting the formation of these osteoclast-like cells. The
      expression of c-src, c-fms, and macrophage colony stimulating factor (M-CSF) was
      induced by TPA treatment; however, TPA-induced M-CSF gene transcription was
      attenuated by the subsequent addition of 1,25-(OH)2D3. Furthermore, both
      dexamethasone and IFN-gamma impaired the attenuation of M-CSF expression,
      suggesting that the transient expression of M-CSF may be important for the
      formation of osteoclast-like cells.

PMID- 9015757
TI  - Structural analysis and characterization of tissue and hormonal responsive
      expression of the avian bone sialoprotein (BSP) gene.
AB  - Bone sialoprotein (BSP) is an extracellular matrix protein that has a highly
      restricted expression to mineralized skeletal tissues. The chicken bone
      sialoprotein-encoding gene (bsp) was isolated and shown to contain two less exons
      than similar mammalian genes, with the absence of an untranslated 5' exon and the
      fusion of the first two exons that encode the signal peptide and amino terminal
      end of the mature BSP peptide. Primer extension analysis showed one strong
      transcriptional start point (tsp) in mRNA prepared from embryonic bone.
      Comparison of the avian bsp promoter sequence to those of other genes expressed
      in vertebrate skeletal tissues, identified the presence of homeobox protein
      binding sequence motifs for engrailed (en-1) and Msx 2 (Hox 8.1), and two
      collagen type II gene silencer elements. Two TATA sequences one at -21 bp and the
      second at -172 bp to the tsp were identified. For the first TATA element no CCAAT
      sequence was observed at an appropriate cis position however two Sp1 sequences
      (GGGCGG) were identified at -66 and -85 bp. A CCAAT element was seen in an
      appropriate cis position in relationship to the second upstream TATA, but
      transient expression analysis in embryonic chicken calvaria osteoblasts using two
      separate promoter/reporter constructs (+24 to -1244 bp or -121 to -1244 bp),
      confirmed that only the proximal TATA and Sp1 elements were functional. The +24
      to -1244 bp promoter sequence demonstrated 33.6, 13.2, and 3.2 fold activity
      above base line respectively, within cells prepared from embryonic chicken
      calvaria bone, cephalic sterna, a cartilage that undergoes mineralization and
      caudal sterna, a cartilage that does not mineralize during embryogenesis. Only
      base line activity was observed within cells prepared from embryonic dermal
      fibroblasts a non-skeletal tissue, which does not express BSP. These same cells
      demonstrated comparable steady state mRNA levels, corroborating that this segment
      of promoter DNA had tissue specific activity. A series of nested deletions from
      the 5' end of the -1244 construct demonstrated that a portion of the tissue
      specific regulation was controlled by the presence of a silencer element(s)
      between -1244 and -620 bp since deletion of this segment of DNA resulted in a 6
      fold increase in the promoter activity in dermal skin fibroblasts. The -1244
      (+)24 nt promoter construct was shown to be stimulated by dexamethasome
      approximately 1.5 fold over control, inhibited by 1,25(OH)2D3 approximately 60%
      of control and was strongly stimulated approximately 5.0 fold by parathyroid
      hormone (PTH) in embryonic calvaria osteoblasts. These data define the proximal
      promoter of the avian bsp gene and identify several potential regulatory elements
      that have been observed in the promoters of other genes expressed in skeletal
      tissues. These elements imparted both tissue and hormone specific promoter
      activity to bsp expression within skeletal cells.

PMID- 9015758
TI  - Tissue-specific protein-DNA interactions of the mouse protamine 2 gene promoter.
AB  - During spermiogenesis, the haploid phase of spermatogenesis, the genome is
      packaged into a highly compacted form and this process requires replacement of
      histones by protamines. In the mouse, protamines are encoded by two genes, which
      are transcriptionally regulated in testis. To understand the regulation of
      transcription of the mouse protamine 2 (mP2) gene, the tissue-distribution of
      sequence-specific interactions between nuclear proteins and promoter DNA
      sequences have been analyzed. Protein binding to the promoter region from -370 to
      +65 was studied using DNase I footprinting and gel shift assays. Five protein
      binding sites were identified, which are recognized by nuclear proteins from
      either testis or liver. Site 1 from -64 to -48, contains part of a cAMP
      responsive element (CRE), which in testis is recognized by CREM tau, an activator
      of post-meiotic transcription. Testicular protein(s) also binds to three other
      promoter domains: site 2, -87 to -67, a region containing a CAAT box, and sites 4
      and 5, -239 to -210 and -328 to -311, sequences with similarity to consensus
      steroid hormone responsive elements (HRE). In contrast, interactions between the
      mP2 promoter and nuclear factors from liver, a tissue in which the mP2 gene is
      not transcribed, are observed at sites 1, 2, and 4, as well as at an additional
      region at site 3, -202 to -175. Because occupancy at site 3 appears to correlate
      with inactivation of the gene in non-testicular tissues, whereas testicular
      protein binding at site 5 appears to be associated with active transcription, we
      conclude that the mP2 promoter displays intricate tissue-specific patterns of
      protein/DNA interactions at key regulatory elements.

PMID- 9015759
TI  - Detection of a proliferation specific gene during development of the osteoblast
      phenotype by mRNA differential display.
AB  - Fetal rat calvarial-derived osteoblasts in vitro (ROB) reinitiate a developmental
      program from growth to differentiation concomitant with production of a bone
      tissue-like organized extracellular matrix. To identify novel genes which may
      mediate this sequence, we isolated total RNA from three stages of the cellular
      differentiation process (proliferation, extracellular matrix maturation, and
      mineralization), for screening gene expression by the differential mRNA display
      technique. Of 15 differentially displayed bands that were analyzed by Northern
      blot analysis, one prominent 310 nucleotide band was confirmed to be
      proliferation-stage specific. Northern blot analysis showed a 600-650 nt
      transcript which was highly expressed in proliferating cells and decreased to
      trace levels after confluency and throughout the differentiation process. We have
      designated this transcript PROM-1 (for proliferating cell marker). A full length
      PROM-1 cDNA of 607 bp was obtained by 5' RACE. A short open reading frame encoded
      a putative 37 amino acid peptide with no significant similarity to known
      sequences. Expression of PROM-1 in the ROS 17/2.8 osteosarcoma cell line was
      several fold greater than in normal diploid cells and was not downregulated when
      ROS 17/2.8 cells reached confluency. The relationship of PROM-1 expression to
      cell growth was also observed in diploid fetal rat lung fibroblasts. Hydroxyurea
      treatment of proliferating osteoblasts blocked PROM-1 expression; however, its
      expression was not cell cycle regulated. Upregulation of PROM-1 in response to
      TGF-beta paralleled the stimulatory effects on growth as quantitated by histone
      gene expression. In conclusion, PROM-1 represents a small cytoplasmic polyA
      containing RNA whose expression is restricted to the exponential growth period of
      normal diploid cells; the gene appears to be deregulated in tumor derived cell
      lines.

PMID- 9015760
TI  - Effect of tumor necrosis factor-alpha on the phosphorylation of tyrosine kinase
      receptors is associated with dynamic alterations in specific protein-tyrosine
      phosphatases.
AB  - Tumor necrosis factor-alpha (TNF-alpha) can modulate the signalling capacity of
      tyrosine kinase receptors; in particular, TNF-alpha has been shown to mediate the
      insulin resistance associated with animal models of obesity and noninsulin
      dependent diabetes mellitus. In order to determine whether the effects of TNF
      alpha might involve alterations in the expression of specific protein-tyrosine
      phosphatases (PTPases) that have been implicated in the regulation of growth
      factor receptor signalling, KRC-7 rat hepatoma cells were treated with TNF-alpha,
      and changes in overall tissue PTPase activity and the abundance of three major
      hepatic PTPases (LAR, PTP1B, and SH-PTP2) were measured in addition to effects of
      TNF-alpha on ligand-stimulated autophosphorylation of insulin and epidermal
      growth factor (EGF) receptors and insulin-stimulated insulin receptor substrate-1
      (IRS-1) phosphorylation. TNF-alpha caused a dose-dependent decrease in insulin
      stimulated IRS-1 phosphorylation and EGF-stimulated receptor autophosphorylation
      to 47-50% of control. Overall PTPase activity in the cytosol fraction did not
      change with TNF-alpha treatment, and PTPase activity in the particulate fraction
      was decreased by 55-66%, demonstrating that increases in total cellular PTPase
      activity did not account for the observed alterations in receptor signalling.
      However, immunoblot analysis showed that TNF-alpha treatment resulted in a 2.5
      fold increase in the abundance of SH-PTP2, a 49% decrease in the transmembrane
      PTPase LAR, and no evident change in the expression of PTP1B. These data suggest
      that at least part of the TNF-alpha effect on pathways of reversible tyrosine
      phosphorylation may be exerted through the dynamic modulation of the expression
      of specific PTPases. Since SH-PTP2 has been shown to interact directly with both
      the EGF receptor and IRS-1, increased abundance of this PTPase, may mediate the
      TNF-alpha effect to inhibit signalling through these proteins. Furthermore,
      decreased abundance of the LAR PTPase, which has been implicated in the
      regulation of insulin receptor phosphorylation, may account for the less marked
      effect of TNF-alpha on the autophosphorylation state of the insulin receptor
      while postreceptor actions of insulin are inhibited.

PMID- 9015761
TI  - Age-related changes in bone formation, osteoblastic cell proliferation, and
      differentiation during postnatal osteogenesis in human calvaria.
AB  - We have determined the age-related changes in the growth characteristics and
      expression of the osteoblast phenotype in human calvaria osteoblastic cells in
      relation with histologic indices of bone formation during postnatal calvaria
      osteogenesis. Histomorphometric analysis of normal calvaria samples obtained from
      36 children, aged 3 to 18 months, showed an age-related decrease in the extent of
      bone surface covered with osteoblasts and newly synthesized collagen,
      demonstrating a progressive decline in bone formation during postnatal calvaria
      osteogenesis. Immunohistochemical analysis showed expression of type I collagen,
      bone sialoprotein, and osteonectin in the matrix and osteoblasts, with no
      apparent age-related change during postnatal calvaria osteogenesis. Cells
      isolated from human calvaria displayed characteristics of the osteoblast
      phenotype including alkaline phosphatase (ALP) activity, osteocalcin (OC)
      production, expression of bone matrix proteins, and responsiveness to
      calciotropic hormones. The growth of human calvaria osteoblastic cells was high
      at 3 months of age and decreased with age, as assessed by (3H)-thymidine
      incorporation into DNA. Thus, the age-related decrease in bone formation is
      associated with a decline in osteoblastic cell proliferation during human
      calvaria osteogenesis. In contrast, ALP activity and OC production increased with
      age in basal conditions and in response to 1,25(OH)2 vitamin D3, suggesting a
      reciprocal relationship between cell growth and expression of phenotypic markers
      during human postnatal osteogenesis. Finally, we found that human calvaria
      osteoblastic cells isolated from young individuals with high bone formation
      activity in vivo and high growth potential in vitro had the ability to form
      calcified nodular bone-like structures in vitro in the presence of ascorbic acid
      and beta-glycerophosphate, providing a new model to study human osteogenesis in
      vitro.

PMID- 9015762
TI  - Binding site on human C-reactive protein (CRP) recognized by the leukocyte CRP
      receptor.
AB  - C-reactive protein (CRP), the prototypical inflammatory acute phase reactant in
      humans, interacts with monocytes and neutrophils via a specific receptor. To map
      the site on CRP recognized by the CRP receptor (CRP-R), synthetic peptides
      corresponding to the surface region on each of the five identical subunits were
      tested as competitors vs. [125I]-CRP for cell binding. A peptide of residues 27
      38 (TKPLKAFTVCLH) efficiently inhibited CRP binding when compared to other
      nonoverlapping peptides. This peptide was termed the cell-binding peptide (CB
      Pep). The F(ab')2 of an IgG Ab to the CB-Pep specifically inhibited CRP binding
      upon reacting with the ligand. Competitive binding studies with synthetic
      peptides truncated from either the NH2- or COOH-terminus of the CB-Pep revealed
      that the minimum length recognized by the CRP-R consisted of residues 31-36:
      KAFTVC. Conservative substitutions of residues within the CB-Pep indicated that
      the four residues AFTV were critical for CRP-R binding. The CB-Pep also inhibited
      induced superoxide generation by HL-60 granulocytes. The minimum length required
      for the inhibition was also KAFTVC; however, only Phe-33 and Leu-37 were critical
      residues in this assay. Anti-CB-Pep IgG Ab reacted more extensively with heat
      modified CRP, suggesting that an altered conformation of CRP is preferentially
      recognized by the CRP-R. The results suggest that this contiguous sequence on a
      beta-strand on one face of each of five subunits of the CRP pentamer serves as a
      unique recognition motif for inflammatory leukocytes.

PMID- 9015763
TI  - Meiosis reinitiation of mussel oocytes involves L-type voltage-gated calcium
      channel.
AB  - In the present work we assessed the involvement of L-type voltage opening Ca2+
      channels in KCl-induced meiosis reinitiation of metaphase-arrested blue mussel
      (Mytilus galloprovincialis) oocytes by performing binding assays with a tritiated
      dihydropyridine analog (+)PN 200110. Our data reveal the existence of a single
      class of dihydropyridine receptors in plasma membrane-enriched rough microsome
      preparations of mussel oocytes. The apparent affinity (Kd) of characterized
      receptors equals 1.32 +/- 0.21 microM while their maximal binding capacity (Bmax)
      is 620 +/- 150 pmol/mg protein. The comparison of the rank order of potency of
      analogs tested to: 1) inhibit [(+)-[3H]PN 200110 specific binding and 2) block
      KCl-induced meiosis reinitiation pointed to the pharmacological profile similar
      to but not identical with those previously described for mammalian
      dihydropyridine receptors. The efficiencies of all antagonists tested are
      linearly related (r = 0.995) in binding-(inhibition of [(+)-[3H]PN 200110
      specific binding) and biological (inhibition of meiosis reinitiation) assays thus
      arguing for functional involvement of L-type Ca2+ channels in oocyte activation.
      Reversibility of antagonist actions on meiosis reinitiation and dependence of
      receptor binding characteristics on a membrane polarization state further
      suggested such a role.

PMID- 9015764
TI  - Multiple G-protein involvement in parathyroid hormone regulation of acid
      production by osteoclasts.
AB  - The involvement of multiple G-proteins in parathyroid hormone regulation of acid
      production was demonstrated in a highly enriched osteoclast population.
      Osteoclasts were isolated from the endosteum of 2.5 to 3-week-old chicken tibia
      using sequential enzymatic digestion. Single cell analysis of acid production was
      accomplished using microscope photometry and vital staining with acridine orange,
      a hydrogen ion concentration sensitive fluorescent dye. Lithium chloride, an
      uncoupler of G-proteins from their respective receptors, blocked parathyroid
      hormone stimulated production of acid. Cholera toxin, which permanently activates
      Gs-proteins, mimicked PTH stimulation. Pertussis toxin, which prevents receptor
      interaction with Gi- and Go-proteins, blocked both 10(-8) M and 10(-11) M PTH
      stimulated acid production, suggesting that the pertussis toxin-sensitive G
      protein is utilized at both PTH concentrations. Immunoblots of osteoclast plasma
      membrane proteins, using a panel of antibodies generated against specific G
      protein alpha subunits, revealed a 48 kDa Gs alpha, a 41 kDa Go alpha, a 34 kDa
      Gi alpha-3, and a unique 68 kDa G alpha subunit, with the 41 kDa and 34 kDa bands
      being the most intense. Immunoblots of osteoblast plasma membrane proteins had a
      substantially different profile with the most intense bands being a Gs alpha (48
      kDa) and a Go alpha (36 and 38 kDa). The studies suggest the utilization of at
      least two different G-proteins in the parathyroid hormone regulation of acid
      formation by osteoclasts, a Gs and a pertussis toxin-sensitive G-protein (Go
      and/or Gi alpha-3).

PMID- 9015776
TI  - Effect of allergen specific immunotherapy (IT) on natural killer cell activity
      (NK), IgE, IFN-gamma levels and clinical response in patients with allergic
      rhinitis and asthma.
AB  - Allergen specific immunotherapy (IT) has been widely used for many years as a
      specific treatment of allergic diseases. A variety of changes in immunological
      parameters have been described but it still remains uncertain as to which of them
      is responsible for the improvement of symptoms. The aim of our study was to
      evaluate the effect of IT on natural killer (NK) cell activity, IL-4, IFN-gamma,
      IgE levels and skin test reactivity in addition to clinical efficacy. Thirty-one
      patients with allergic rhinitis and asthma were selected according to positive
      history, skin prick tests to Dermatophagoides pteronyssinus (Der p) or grass
      pollens, presence of specific IgE antibodies in sera and clinical findings, and
      were submitted to one year of placebo-controlled IT. Total IgE, specific IgE, IL
      4 and IFN-gamma levels were measured by using ELISA method. Standard chromium 51
      release assay was used to measure NK cell cytotoxic activity against the human
      leukemic cell line, K562 target cells. Mean symptom and medication scores, skin
      test reactivity and histamine sensitivity were significantly decreased in the
      patients given IT at the end of the first year when compared with the placebo
      group. However, there was neither a significant reduction in total and specific
      IgE levels nor a significant increase in IFN-gamma levels at the first year of
      IT. IL-4 levels were only measured at the beginning of the study because of the
      very low levels. A decrease in NK cell activity was found in patients treated
      with grass pollen extracts after 12 months when compared with Der p and placebo
      group. No signs of major local or systemic side effects due to IT were seen in
      patients during the study. Although significant clinical efficacy of specific IT
      with standardized extracts has been demonstrated in allergic rhinitis and
      asthmatic patients at the end of the first year of IT, no significant changes in
      immunological parameters were observed. However we conclude that a decrease in NK
      cell cytotoxic activity during IT has to be taken into account in the follow-up
      of patients.

PMID- 9015777
TI  - Abuse of therapy with corticosteroids in the asthmatic patient and the deficient
      control of suprarenal function. Indication of therapy with ACTH.
AB  - The use of corticosteroids, either oral, parenteral or as aerosol, means a great
      step forward in bronchial asthma treatment. Nevertheless, given the abuse of
      their administration, we find more and more frequently, cases of corticodependent
      bronchial asthma, due to a deficient control in the clinical evolution. For this
      reason, we performed a study with 39 patients diagnosed with corticodependent
      intrinsic bronchial asthma. Basal cortisol determination was performed in all,
      and all of them followed posttreatment with ACTH, antibiotics and mucolytics, as
      well as follow up of respiratory function parameters and clinical evolution. We
      found a mean increase in cortisol levels of 488% (basal: 2.49 +/- 0.33
      micrograms/dl; posttreatment: 14.59 +/- 2.9 micrograms/dl). Regarding the
      respiratory function tests, FEV1 improved from 59.38 +/- 4.23% to 68.52% +/-
      4.28% (15.4% increase); MEF50 went from 28.62 +/- 3.47% to 35.9 +/- 3.81% (25.4%
      increase) and MEF25-75 improved from 28.89 +/- 3.47% to 37.05 +/- 3.93% (28.2%
      increase). Clinical symptomatology and medication improved in general, going from
      an initial punctuation of 8.5 to a posttreatment score of 7.47. In general, 50%
      of the patients studied improved from the clinical point of view, only 47.2% had
      a discrete improvement, and only one patient got worse. Side effects with ACTH
      treatment appeared in 28.2% of the cases, mainly peripheral edemas, especially in
      the lower extremities. In conclusion, with patients undergoing lengthy
      corticosteroid therapy, control of their suprarenal function is absolutely
      necessary. If a glandular insufficiency appears with low levels of plasmatic
      cortisol, we advise treatment with ACTH in association with antibiotics.

PMID- 9015778
TI  - Beta-endorphin concentrations in the sera of asthmatic patients.
AB  - Recent findings in animals indicate the influence of beta-endorphins on bronchial
      smooth muscle tone. The purpose of our study was to compare beta-endorphin
      concentrations in sera of asthmatics during the asymptomatic period and after
      histamine provocation. The study was performed in a group of 32 asthmatic
      patients and 12 healthy subjects. Beta-endorphin concentrations were evaluated by
      radioimmunoassay (J-125 beta-Endorphin Human) twice daily at 8 a.m. and 10 a.m.,
      and also before and after histamine provocation. No significant differences were
      found in endorphin concentrations for both normal controls and asthmatics at 8
      a.m. and 10 a.m. We demonstrated a statistically significant increase in
      endorphin concentrations in asthmatics as compared to the controls. We found a
      statistically significant decrease of beta-endorphin concentrations after
      histamine provocation in the asthmatic group.

PMID- 9015780
TI  - Specific immunotherapy in pollinosis: II. Forecasting changes in certain
      cytoimmunological indicators after four years of immunotherapy in pollinosis.
AB  - The determination of an appropriate period of duration for specific immunotherapy
      presents an important problem in the treatment of allergic diseases. The aim of
      this paper was to conduct a prognostic study of certain immunological indicators
      after 4 years of desensitization, and to determine which of the tested indicators
      are characteristic for an evaluation of the clinical condition. Individuals with
      pollinosis were tested after the first, second, third and fourth year of
      desensitization using the pollen allergen. The B and T-lymphocyte counts, the
      levels of immunoglobulins A, M, G, and total and specific E, and the volume of
      basal, total and specifically released histamine were all measured. Furthermore,
      the clinical condition of the patient was defined using a score method (0-3
      points), taking into account the results of testing and the basic symptoms of the
      disease. Following this, a prediction of results after the fifth year of
      desensitization was made, using Brown's method of exponential smoothing. The
      majority of the data obtained from the forecasting study indicate that in the
      subsequent fifth year of desensitization, the indicators studied should undergo
      further changes in values, offering a strong argument for the necessity of
      extending the period of immunotherapy in pollinosis beyond three years. In the
      results of the regression function estimates it was determined that, among the
      indicators studied, those which are helpful in monitoring treatment are: T-RFC, T
      FcG-BG, T-FcM-EN and B-EAC lymphocyte counts, levels of IgA, IgM and specific
      IgE, and the percentage of specifically released histamine.

PMID- 9015779
TI  - Local nasal immunotherapy with a powder extract for grass pollen induced rhinitis
      in pediatric ages: a controlled study.
AB  - Forty pediatric patients, ranging from 5-13 years of age and suffering from grass
      pollen rhinoconjunctivitis, were submitted to local nasal preseasonal (12 weeks)
      immunotherapy, either with a grass pollen extract or with placebo. After 1 year,
      15 of these patients (5 previously treated with active product and 10 with
      placebo) were treated with the grass pollen extract preseasonally for 2
      consecutive years. Before and after treatment, serum total IgA and IgE, and
      specific IgG and IgE were assayed as well as carrying out nasal provocation tests
      (NPT) with extracts at different concentrations, endpoint evaluations by
      rhinomanometry and prick tests with different concentrations of extract. After
      only 1 year, the actively treated patients showed a significant decrease of daily
      nasal and conjunctival signs and symptoms-as judged by a 1 to 3 score-in
      comparison with the control group. The placebo group showed the same results
      after the 3rd year. The improvement was confirmed by a significant increase of
      the dose threshold in NPT. No immunological alterations were evident.

PMID- 9015781
TI  - Why are nasal and bronchial symptoms mostly perennial in patients with
      monosensitization to Olea europaea pollen allergens?
AB  - In the last few years interest in the clinical aspects of Olea europaea (O.e.)
      pollen allergy has increased. For many years we have observed in our geographical
      area a perennial pattern of clinical symptoms in subjects with monosensitization
      to O.e. allergens without any worsening during the olive pollen season. We tried
      to demonstrate the clinical relevance of O.e. sensitization in our patients and,
      moreover, to determine why this pattern is elicited. We selected a group of 26
      patients with rhinitis and/or bronchial asthma and an immediate positive skin
      reaction only to O.e. pollen extract. Using commercially available extracts and
      reagents, the following diagnostic procedures were performed: Skin prick tests
      (SPT), specific O.e. IgE assays, nonspecific bronchial provocation tests (NsBPT)
      and specific nasal provocation tests (sNPT), respectively, in patients with
      bronchial asthma and rhinitis. Pollen counts and a statistical analysis using
      Spearman's correlation test were also carried out. 21 of 26 O.e. monosensitive
      patients showed perennial type of clinical symptoms without any particular
      worsening during olive pollination season. We found a high degree of statistical
      significance between the results of SPT/sNPT and serum specific IgE
      determination. Many patients exhibited a late response after sNPT. No definitive
      data were derived from our findings, even though the occurrence of many late
      reactions after sNPT could in part explain the perennial type of nasal symptoms.
      We would like to emphasize the necessity of better purification and
      standardization of diagnostic materials and, moreover, suggest further studies
      with a greater number of O.e. monosensitive patients living in different
      geographical areas.

PMID- 9015782
TI  - An immunoblotting analysis of cross-reactivity between melon, and plantago and
      grass pollens.
AB  - It is known that most patients with type I allergy to pollens also suffer
      intolerance to fruits. Recently, an epidemiological and CAP-inhibition study has
      shown a new clustering of allergy between melon and Plantago and grass pollens.
      The aim of the present study was to confirm these results by immunoblotting
      analysis and inhibition of immunoblotting. Sera from 3 patients with confirmed
      allergy to melon, and Dactylis glomerata and Plantago lanceolata pollens were
      used for the in vitro studies. SDS-PAGE and immunoblotting analysis with a pool
      of sera revealed that several distinct protein bands were shared by the three
      extracts at 14, 31, and a spectrum between 40 and 70 kDa, approximately.
      Immunoblotting inhibition experiments, performed with extracts of melon, Plantago
      and Dactylis, showed that all allergens of melon blotting were almost completely
      inhibited by grass and Plantago pollen extracts. Inversely, the melon extract was
      capable of inhibiting IgE-binding to various allergens of Dactylis at high mol
      mass and partially to the band at 14 kDa. Moreover, the melon almost totally
      inhibited the IgE-binding capacity to the proteins of Plantago extract. Taken
      together, the results support the presence of structurally similar allergens in
      melon, Plantago and grass pollens, and that all allergenic epitopes of the melon
      are present in these pollens.

PMID- 9015783
TI  - Basophil count in neonates is not suitable for atopy predictivity.
AB  - Basophil granulocytes and their mediators are involved in the pathogenesis of
      allergic inflammation. We evaluated basophil count, blood histamine content,
      eosinophil count and serum total IgE levels in one hundred-thirteen healthy
      newborns at birth. 102 children were prospectively studied with a follow up to 18
      months of age for development of atopic disorders. No difference was found in
      newborns with biparental family history of atopy (FHA) in comparison with
      newborns with monoparental FHA and with newborns without FHA. Children who
      developed atopic disorders had neonatal basophil counts higher than those who did
      not develop atopic symptoms (p = 0.03). No significant correlation was found
      between basophil and eosinophil counts (rs = 0.013), between basophil count and
      serum total IgE levels (rs = 0.012) and between basophil count and blood
      histamine content. Positive predictive value and sensitivity of basophil count
      for allergy up to 18 months of age was only 33% and 27%, respectively. Our data
      indicate that an increased basophil count at birth is not associated with FHA and
      is not a good predictive marker of atopy.

PMID- 9015784
TI  - Type IV hypersensitivity to subcutaneous heparin: a new case.
AB  - A 71-year-old woman was seen for cutaneous lesions that appeared on her abdomen
      15 days after the beginning of subcutaneous injection of nadroparin calcium
      (Fraxiparina), a low molecular-weight heparin (LMWH). The lesions were very
      pruriginous, measured 0.5-3 cm, and appeared at and around the point of
      Fraxiparina injection. Fraxiparina treatment was stopped and the lesions subsided
      spontaneously in one week. The patient had been treated with intravenous heparin
      (H) one year before. A 6 mm punch biopsy showed spongiosis and a mild dermal
      superficial perivascular infiltrate composed of lymphocytes and eosinophils. A
      challenge test with a therapeutic dose of Fraxiparina produced a lesion similar
      to those described above. Epicutaneous, prick and intradermal tests with
      undiluted samples of different H (both preservative-containing and preservative
      free) were performed. Patch tests produced a mild erythematous reaction to all H
      at 48 hours and a (++) reaction at 96 hours. These reactions persisted for one
      week. Prick tests showed neither an immediate nor a delayed reaction. Intradermal
      tests with H did not produce an immediate reaction, but induced an infiltrated
      erythematous reaction at 48 hours that enlarged during the next 2 days and was
      transformed into pruritic plaques with vesicles. The lesions cleared in two
      weeks. Our findings confirm a delayed-type hypersensitivity to H and cross
      reactivity between unfractioned and LMWH.

PMID- 9015785
TI  - Candidin in immediate hypersensitivity. Comparison of two antigens.
AB  - One hundred outpatients in a Clinic of Allergy were submitted to intradermic
      tests with two types of candidins. The main focus of the research was the
      comparison of two antigens obtained from the same strains of Candida albicans:
      one a suspension of yeast cells and the other, a polysaccharide. The readings,
      taken 20 minutes after the intradermic injections, with positive results were
      considered as hypersensitivity of the immediate type. Positive results were
      obtained in 74% of the patients with the yeast cell antigen and in 73% with the
      polysaccharide antigen. This research mainly deals with the advantages that can
      be obtained by using the polysaccharide antigen in intradermic tests for
      evaluating hypersensitivity of the immediate type.

PMID- 9015786
TI  - MHC-binding peptide prediction on the Web.

PMID- 9015787
TI  - Chromosomes in colour.

PMID- 9015788
TI  - Tissue-engineered cartilage attracts research interest.

PMID- 9015789
TI  - Attention deficit continues to attract research attention.

PMID- 9015790
TI  - Drug-resistant bacteria: responding to the infectious disease crisis.
AB  - The 1990s have been a period of growing anxiety about the emergence of antibiotic
      resistant bacteria. Public health, society and the research community must
      respond quickly to safeguard existing drugs and develop new ones to prevent
      resistance overwhelming healthcare systems worldwide.

PMID- 9015791
TI  - Signal transduction-based strategies for the treatment of chronic myelogenous
      leukemia.
AB  - Recent studies of the BCR-ABL fusion protein, the product of the oncogene
      responsible for chronic myelogenous leukemia, have identified a number of signal
      transduction pathways that are activated by this tyrosine kinase. In some cases,
      these pathways are critical mediators of the growth stimulatory effects of the
      oncogene on hemopoietic cells. This knowledge has been translated into
      therapeutic strategies that directly target BCR-ABL or the signaling pathways
      that BCR-ABL activates. Promising results in animal models have led to the design
      of Phase I clinical trials, which are in progress or will be under way shortly.
      These studies are among the first to target a specific genetic abnormality in
      human cancer.

PMID- 9015792
TI  - Nitric oxide and atherosclerosis: possible implications for therapy.
AB  - Atherosclerosis and hypercholesterolaemia disturb the endothelium-dependent
      regulation of the vascular tone by the labile liposoluble radical nitric oxide.
      This defect predisposes to vasospasm and ischaemia, with anginal pain as a
      clinical manifestation. It is now appreciated that endothelial dysfunction is an
      early event in atherogenesis, possibly also involving the microcirculation, in
      which atherosclerosis does not develop. Furthermore, it is becoming clear that
      nitric oxide, in addition to regulating vasomotion, might also modulate the
      progression of the disease process. The latter notion could have therapeutic
      implications.

PMID- 9015793
TI  - Replicating viruses as selective cancer therapeutics.
AB  - Replication-competent viruses are used as selective cancer therapeutics and the
      mechanisms leading to tumor-specific replication and antitumoral efficacy are now
      becoming apparent. The specific viruses in development include tumor-targeting
      herpes simplex viruses, autonomous parvoviruses, Newcastle disease viruses and
      adenovirus. Information is also available on antiviral immunology and viral
      defenses against host-mediated immunity. This approach has many potential
      attributes, in addition to potential hurdles that must be overcome.

PMID- 9015794
TI  - Use of positron emission tomography to study tumors in vivo.
AB  - Positron emission tomography (PET) is a non-invasive imaging technique. The
      ability of PET to visualize biochemistry and physiology in vivo distinguishes
      this technique from other imaging modalities and renders it of particular
      interest for oncological studies. PET studies can often differentiate between
      normal and neoplastic tissue, as well as identify early signs of malignant
      degeneration through biochemical or physiological changes. Over the past several
      years, PET studies have been useful in the early diagnosis and the selection of
      treatment, as well as in following the progression or regression of malignant
      disease processes. Of particular significance, PET findings can be quantified by
      using mathematical modeling and computerized data analysis, which makes it
      possible to produce quantitative images of human pathophysiology in vivo.

PMID- 9015795
TI  - Atypical neuroleptics have low affinity for dopamine D2 receptors or are
      selective for D4 receptors.
AB  - This review examines the possible receptor basis of the atypical action of those
      atypical antipsychotic drugs that elicit low levels of Parkinsonism. Such an
      examination requires consistent and accurate dissociation constants for the
      antipsychotic drugs at the relevant dopamine and serotonin receptors. It has long
      been known, however, that the dissociation constant of a given antipsychotic drug
      at the dopamine D2 receptor varies between laboratories. Although such variation
      depends on several factors, it has recently been recognized that the radioligand
      used to measure the competition between the antipsychotic drug and the
      radioligand is an important variable. The present review summarizes information
      on this radioligand dependence. In general, a radioligand of low solubility in
      the membrane (i.e., low tissue:buffer partition) results in a low value for the
      antipsychotic dissociation constant when the drug competes with the radioligand.
      Hence, by first obtaining the antipsychotic dissociation constants using
      different radioligands of different solubility in the membrane, one can then
      extrapolate the data to low or "zero" ligand solubility. The extrapolated value
      represents the radioligand-independent dissociation constant of the
      antipsychotic. These values are here given for dopamine D2 and D4 receptors, as
      well as for serotonin 5-HT2A receptors. These values, moreover, agree with the
      dissociation constant directly obtained with the radioactive antipsychotic
      itself. For example, clozapine revealed a radioligand-independent value of 1.6 nM
      at the dopamine D4 receptor, agreeing with the value directly measured with [3H]
      clozapine at D4. However, because clozapine competes with endogenous dopamine,
      the in vivo concentration of clozapine (to occupy dopamine D4 receptors) can be
      derived to be about 13 nM, agreeing with the value of 12 to 20 nM in the plasma
      water or spinal fluid observed in treated patients. The atypical neuroleptics
      remoxipride, clozapine, perlapine, seroquel, and melperone had low affinity for
      the dopamine D2 receptor (radioligand-independent dissociation constants of 30 to
      90 nM). Such low affinity makes these latter five drugs readily displaceable by
      high levels of endogenous dopamine in the caudate or putamen. Most typical
      neuroleptics have radioligand-independent values of 0.3 to 5 nM at dopamine D2
      receptors, making them more resistant to displacement by endogenous dopamine.
      Finally, a relation was found between the neuroleptic doses for rat catalepsy and
      the D2:D4 ratio of the radioligand-independent K values for these two receptors.
      Thus, the atypical neuroleptics appear to fall into two groups, those that have a
      low affinity for dopamine D2 receptors and those that are selective for dopamine
      D4 receptors.

PMID- 9015796
TI  - Tardive dyskinesia exacerbated after ingestion of phenylalanine by schizophrenic
      patients.
AB  - Despite continued research, the influences that promote or exacerbate tardive
      dyskinesia (TD) symptoms remain incompletely understood. Recent findings (Gardos
      et al. 1992; Richardson et al. 1989) suggest that ingestion of the dietary
      constituent, phenylalanine, might exacerbate TD symptoms, but a double-blind,
      placebo-controlled challenge had not previously been conducted in schizophrenic
      patients. On two different mornings, in counterbalanced order, 18 male
      schizophrenic patients with TD were challenged with either 100 mg/kg
      phenylalanine or placebo. Effects on abnormal involuntary movements, recall
      memory, and plasma phenylalanine were measured 90 minutes post-challenge. The
      results supported the hypothesis in that involuntary movements increased to a
      statistically and clinically meaningful degree after the phenylalanine challenge,
      but not after placebo. No effects on memory were detected. Significant order
      effects characterized the plasma findings but not the behavioral data. Results
      indicate that a dietary constituent, the amino acid phenylalanine, can
      potentially exacerbate tardive dyskinesia symptoms in schizophrenic patients. The
      influence of phenylalanine and other ingested substances on clinical
      symptomatology warrants further investigation.

PMID- 9015797
TI  - Sensitization of the locomotor response to psychostimulants after repeated opiate
      exposure: role of the nucleus accumbens.
AB  - The following experiments were performed to ascertain the role of the nucleus
      accumbens in opiate-dopamine interactions using measures of locomotor activity.
      Three separate experiments were carried out. In Experiment 1, rats received
      systemic morphine (10 mg/kg IP) or saline (1 ml/kg IP) every other day for 5
      days, followed by systemic amphetamine (1.5 mg/kg) 48 hours following the fifth
      injection. Animals in the morphine pretreatment group exhibited a sensitized
      locomotor response to amphetamine. In Experiment 2, animals received the same
      systemic pretreatment and were subsequently given intraaccumbens saline,
      amphetamine (2.5 micrograms/0.5 microliter) or cocaine (7 micrograms/0.5
      microliter), each separated by 48 hours. Morphine-pretreated animals showed
      enhanced motor activity in response to intraaccumbens microinfusion of the
      psychostimulant drugs. Finally, in Experiment 3, multiple microinjections of
      morphine (0.5 microgram/0.5 microliter) directly into the nucleus accumbens
      resulted in a potentiated locomotor response to intraaccumbens amphetamine (2.5
      micrograms/0.5 microliter). These data indicate that the nucleus accumbens may
      contribute to both the development and expression of opiate-stimulant cross
      sensitization. The neural basis of this sensitization is hypothesized to be a
      common intracellular pathway affected by both classes of drugs, such as the
      cyclic adenosine monophosphate (AMP) system.

PMID- 9015798
TI  - Acute blockade of corticosterone secretion decreases the psychomotor stimulant
      effects of cocaine.
AB  - Previous reports have shown that long-term blockade of corticosterone secretion,
      by either adrenalectomy or repeated treatment with an inhibitor of corticosterone
      synthesis, metyrapone, profoundly reduces sensitivity to drugs of abuse. In this
      report we investigated whether acute blockade of corticosterone secretion has
      similar effects. Animals received a single injection of metyrapone (50 mg/kg SC)
      and were tested for their locomotor response to cocaine (15 mg/kg IP) 3 hours
      later. Acute metyrapone treatment reduced the locomotor response to cocaine by
      about 50%, and this effect was reversed by corticosterone (20 mg/kg SC). The
      behavioral effects of these treatments paralleled changes in plasma
      corticosterone levels 20 minutes after an injection of cocaine. Despite the
      differences in behavior and corticosterone levels, the brain levels of cocaine in
      these groups did not differ. These results indicate that the behavioral effects
      of cocaine can be modified by an acute pharmacological manipulation of
      corticosterone secretion.

PMID- 9015799
TI  - Serotonin receptors in suicide victims with major depression.
AB  - Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been
      implicated in the pathophysiology of suicide. Brain samples were collected at
      autopsy from suicide victims with a current episode of major depression and
      matched comparison subjects who died of natural or accidental causes.
      Retrospective psychiatric assessments were collected from knowledgeable
      informants for all suicide victims and most of the comparison subjects.
      Psychiatric diagnoses were determined according to DSM-III-R criteria. Any
      subjects with current psychoactive substance use disorders were excluded.
      Quantitative receptor autoradiography was used in serial sections of the right
      prefrontal cortex (area 10) and hippocampus to measure the binding of [3H]8
      hydroxy-2-(di-n-propyl)-aminotetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and
      [3H]ketanserin to 5-HT2A receptors. Analysis of covariance was used to compare
      control subjects and suicide victims with major depression. The age of subjects,
      the time from death to freezing the tissue (postmortem interval), and the storage
      time of tissues in the freezer were used as covariates in the analyses. There
      were no significant differences between suicide victims with major depression and
      comparison subjects in 5-HT1A or 5-HT2A receptors in area 10 of the right
      prefrontal cortex or the hippocampus. The current results suggest that the number
      of 5-HT1A and 5-HT2A receptors in the right prefrontal cortex (area 10) or
      hippocampus are not different in suicide victims with major depression.

PMID- 9015800
TI  - Dopamine D2 receptor availability in opiate-dependent subjects before and after
      naloxone-precipitated withdrawal.
AB  - Dopamine may play a role in opiate withdrawal and dependence. We measured
      dopamine D2 receptor availability in 11 opiate-dependent subjects using PFT and
      [11C]raclopride at baseline and during naloxone-precipitated withdrawal. Because
      [11C]raclopride is sensitive to endogenous dopamine, this strategy enabled us to
      test whether we could document in humans the DA reductions reported in animal
      models of opiate withdrawal. Results were compared with values from 11 controls,
      two of which also received naloxone. The ratio of the distribution volume in
      striatum to that in cerebellum (Bmax/Kd + 1) was used as model parameter for D2
      receptor availability. Baseline measures for Bmax/Kd were lower in opiate
      dependent subjects (2.44 +/- 0.4) than in controls (2.97 +/- 0.45 P < or = .009).
      Naloxone precipitated an intense withdrawal in the abusers but did not change the
      Bmax/Kd ratio. This study documents decreases in D2 receptors in opiate-dependent
      subjects but does not document significant changes in striatal DA concentration
      during acute withdrawal.

PMID- 9015801
TI  - Molar quantitation of hepatic metabolites in vivo in proton-decoupled, nuclear
      Overhauser effect enhanced 31P NMR spectra localized by three-dimensional
      chemical shift imaging.
AB  - Proton decoupling and nuclear Overhauser effect (NOE) enhancement significantly
      improve the signal-to-noise ratio and enhance resolution of metabolites in in
      vivo 31P MRS. We obtained proton-decoupled, NOE-enhanced, phospholipid-saturated
      31P spectra localized to defined regions within the normal liver using three
      dimensional chemical shift imaging. Proton-decoupling resulted in the resolution
      of two major peaks in the phosphomonoester (PME) region, three peaks in the
      phosphodiester (PDE) region and a diphosphodiester peak. In order to obtain molar
      quantitation, we measured the NOE of all hepatic phosphorus resonances, and we
      corrected for saturation effects by measuring hepatic metabolite T1 using the
      variable nutation angle method with phase-cycled, B1-independent rotation,
      adiabatic pulses. After corrections for saturation effects, NOE enhancement, B1
      variations and point spread effects, the following mean concentrations (mmol/l of
      liver) (+/-SD) were obtained: [PME1] = 1.2 +/- 0.4, [PME2 + 2,3-DPG] = 1.1 +/-
      0.1, [Pi + 2,3-DPG] = 2.8 +/- 0.5, [GPEth] = 2.8 +/- 0.7, [GPChol] = 3.5 +/- 0.6
      and [beta-NTP] = 3.8 +/- 0.3. T1 and NOE enhancement were strongly correlated (r
      = 90), and indicated that the fractional contribution of 1H-31P dipolar
      relaxation to total 31P relaxation is minimal for NTPs, moderate for PMEs and
      high for PDEs in liver. Proton-decoupling and NOE enhancement permit one to
      obtain more information about in vivo metabolism of liver than previously
      available and should enhance the utility of 31P MRS for the study of hepatic
      disorders.

PMID- 9015802
TI  - Development of a rapid and efficient magnetic resonance imaging technique for
      analysis of body fat distribution.
AB  - Fast scan magnetic resonance imaging techniques for adipose tissue (AT)
      quantification were compared to a conventional T1-weighted spin-echo (SE)
      sequence (TR = 500 ms, TE = 20 ms), imaging a mid-abdominal slice. A rapid T1
      weighted SE sequence (TR = 36 ms, TE = 14 ms) was optimal, with minimal
      distortion (field, motion, flow artefact). Tissue contrast was higher and
      visceral AT was clearly differentiated. Quantification of all AT compartments
      (total, subcutaneous, internal, visceral) showed close agreement with the T1
      weighted SE sequence and reproducibility was high (coefficient of variation <
      4.7%). For AT quantification in a whole subject, this fast technique allows each
      image to be acquired serially at the magnet isocenter, as the subject is moved
      through the scanner (serial isocenter scanning, SIS). This method provides
      minimal image distortion and allows rapid coverage of the whole body.

PMID- 9015803
TI  - ADP recovery after a brief ischemic exercise in normal and diseased human muscle-
      a 31P MRS study.
AB  - The pattern of cytosolic ADP recovery after exercise has not been fully
      characterized in human skeletal muscle. ADP recovery after brief, ischemic
      exercise was studied by 31phosphorus magnetic resonance spectroscopy in calf
      muscles of 33 normal control subjects, four patients with McArdle's disease and
      13 patients with mitochondrial myopathy. In normal muscle, the half-time for the
      initial ADP decline was 0.18 +/- 0.07 min and was unaffected by the pH or the
      metabolic state at the end of exercise. ADP decreased to below rest values during
      the second min of recovery in 27 out of 33 control subjects. There was a
      significant (p < 0.001) linear correlation for both the size (r = 0.65) and
      duration (r = 0.64) of this ADP undershoot with intracellular pH. Phosphocreatine
      resynthesis continued during the ADP undershoot. ADP undershoot was also found in
      patients with mitochondrial diseases (in 11 out of 13), but not McArdle's disease
      (six patients). Thus ADP recovery follows a complex time course that is partly
      dependent on pH. Only the initial ADP recovery is independent of pH, which makes
      it suitable for comparative assessment of muscle mitochondrial function in vivo.
      As phosphocreatine recovery continues during the ADP undershoot, mitochondrial
      regulation must be different from that at the onset of recovery. These
      observations are consistent with variable, changing regulators of mitochondrial
      metabolism in human skeletal muscle.

PMID- 9015804
TI  - Inhibition of tumor cell proliferation by dexamethasone: 31P NMR studies of RIF-1
      fibrosarcoma cells perfused in vitro.
AB  - The impact on tumor cell metabolism of a substantial reduction in cell
      proliferation rate without acute cytotoxicity was examined in cultured RIF-1
      tumor cells following treatment with an antiproliferative steroid, dexamethasone
      (DEX). After 48 h exposure to 4 mM DEX, acute cell viability was essentially
      unchanged: cells were 93 +/- 2% trypan blue excluding in both control and treated
      cultures (all values are mean +/- SD). The fraction of actively proliferating
      cells in the S phase (as indicated by incorporation of 5-bromodeoxyuridine) was
      only 4 +/- 3%, compared with 13 +/- 3% in age-matched control cultures (n =4,
      paired t-test: p < 0.004) and 23 +/- 7% at the beginning of the treatment. Three
      days of DEX treatment resulted in a limited increase in the level of apoptosis
      (programmed cell death): cells did not become rounded or detached, but the
      fraction expressing apoptotic DNA fragmentation (susceptible to nick end labeling
      by terminal deoxy-nucleotidyl transferase) was 15 +/- 7%, vs 2 +/- 1% in control
      cultures (p < 0.02). Despite a 75% inhibition of cell proliferation, DEX caused
      only a modest change in the 31P NMR spectra of RIF-1 cells in vitro. The ratio of
      phosphocreatine to nucleoside triphosphates (NTP) was 30% higher, on average, in
      treated than in control cells (n = 8, paired t-test, p < 0.02), even when both
      treated and control cell densities were low. The level of total phosphomonoester
      (relative to NTP) was lower at low cell density, but this was independent of
      whether cells were growing rapidly (control low density) or were growth inhibited
      by DEX. Neither the ratio of phosphocholine to NTP nor the intracellular pH was
      significantly different in DEX-treated cells.

PMID- 9015805
TI  - Chemical shift imaging of human colorectal tissue (ex vivo).
AB  - The spatial location of MR visible lipid in the wall of the normal human colon,
      and in carcinomatous colonic tissue has been documented using proton chemical
      shift imaging, one- and two-dimensional magnetic resonance spectroscopy and
      histochemical staining. Following dissection of the mucosal and submucosal layers
      of normal colon, these techniques showed high levels of neutral lipid distributed
      in the submucosal layer. Relatively less lipid was observed in the mucosal layer.
      Histochemical staining confirmed that the majority of the neutral lipid was in
      the submucosa, extracellular, and in the lymphatic channels. Carcinomatous tissue
      gave a variable lipid signal which histochemical staining identified as being
      from tumour stroma, necrotic and degenerate tumour cells and macrophages.

PMID- 9015806
TI  - X-ray detectors for digital radiography.
AB  - Digital radiography offers the potential of improved image quality as well as
      providing opportunities for advances in medical image management, computer-aided
      diagnosis and teleradiology. Image quality is intimately linked to the precise
      and accurate acquisition of information from the x-ray beam transmitted by the
      patient, i.e. to the performance of the x-ray detector. Detectors for digital
      radiography must meet the needs of the specific radiological procedure where they
      will be used. Key parameters are spatial resolution, uniformity of response,
      contrast sensitivity, dynamic range, acquisition speed and frame rate. The
      underlying physical considerations defining the performance of x-ray detectors
      for radiography will be reviewed. Some of the more promising existing and
      experimental detector technologies which may be suitable for digital radiography
      will be considered. Devices that can be employed in full-area detectors and also
      those more appropriate for scanning x-ray systems will be discussed. These
      include various approaches based on phosphor x-ray converters, where light quanta
      are produced as an intermediate stage, as well as direct x-ray-to-charge
      conversion materials such as zinc cadmium telluride, amorphous selenium and
      crystalline silicon.

PMID- 9015807
TI  - Wavelengths for port wine stain laser treatment: influence of vessel radius and
      skin anatomy.
AB  - Recent Monte Carlo computations in realistic port wine stain (PWS) models
      containing numerous uniformly distributed vessels suggest equal depth of vascular
      injury at wavelengths of 577 and 585 nm. This finding contradicts clinical
      experience and previous theory. From a skin model containing normal and PWS
      vessels in separate dermal layers, we estimate analytically the average
      volumetric heat production in the deepest targeted PWS vessel. The fluence rate
      distribution is approximated by Beer's law, which depends upon the tissue's
      effective attenuation coefficient, and includes a homogeneous fractional
      volumetric blood concentration corrected for finite-size blood vessels. The model
      predicts 585-587 nm wavelengths are optimal in adult PWSs containing at least one
      layer of small-radius blood vessels. In superficial PWSs, typically in young
      children with small-radius vessels, 577-580 nm wavelengths are optimal.
      Wavelength-independent results similar to those from Monte Carlo models are valid
      in single-layered PWSs of large-radius vessels. In conclusion, the volumetric
      heat production in the deepest targeted PWS blood vessel can be maximized on an
      individual patient basis. However, absorption of 585-587 nm wavelengths is
      sufficiently high in superficial lesions, so we hypothesize that these
      wavelengths may be considered adequate for the treatment of any PWS.

PMID- 9015808
TI  - Modelling light distributions of homogeneous versus discrete absorbers in light
      irradiated turbid media.
AB  - Laser treatment of port wine stains has often been modelled assuming that blood
      is distributed homogeneously over the dermal volume, instead of enclosed within
      discrete vessels. The purpose of this paper is to analyse the consequences of
      this assumption. Due to strong light absorption by blood, fluence rate near the
      centre of the vessel is much lower than at the periphery. Red blood cells near
      the centre of the vessel therefore absorb less light than those at the periphery.
      Effectively, when distributed homogeneously over the dermis, fewer red blood
      cells would produce the same absorption as the actual number of red blood cells
      distributed in discrete vessels. We quantified this effect by defining a
      correction factor for the effective absorbing blood volume of a single vessel.
      For a dermis with multiple vessels, we used this factor to define an effective
      homogeneous blood concentration. This was used in Monte Carlo computations of the
      fluence rate in a homogeneous skin model, and compared with fluence rate
      distributions using discrete blood vessels with equal dermal blood concentration.
      For realistic values of skin parameters the homogeneous model with corrected
      blood concentration accurately represents fluence rates in the model with
      discrete blood vessels. In conclusion, the correction procedure simplifies the
      calculation of fluence rate distributions in turbid media with discrete
      absorbers. This will allow future Monte Carlo computations of, for example,
      colour perception and optimization of vascular damage by laser treatment of port
      wine stain models with realistic vessel anatomy.

PMID- 9015809
TI  - Magnetic fields from domestic appliances in the UK.
AB  - In a survey of 50 UK homes the 50 Hz fundamental and harmonic magnetic fields
      generated by 806 domestic appliances found in the homes, and used regularly by
      mothers, were measured. Measurements were made in the direction of most likely
      access, and from the surface of the appliances. Mothers completed a questionnaire
      on the use of appliances and were monitored for 24 h so that acquired exposure
      could be compared with the measured ambient fields in the home. Appliances were
      measured at standard distances and an algorithm was used to calculate fields at
      100 and 50 cm to remove room background contributions. A few appliances generated
      fields in excess of 0.2 microT at 1 m: microwave cookers 0.37 +/- 0.14 microT;
      washing machines 0.27 +/- 0.14 microT; dishwashers 0.23 +/- 0.13 microT; some
      electric showers 0.11 +/- 0.25 microT and can openers 0.20 +/- 0.21 microT. Of
      continuously operating devices, only central heating pumps (0.51 +/- 0.47
      microT), central heating boilers (0.27 +/- 0.26 microT) and fish-tank air pumps
      (0.32 +/- 0.09 microT) produced significant fields at 0.5 m. There were no
      obvious ways to group different types of appliances as high- or low-strength
      sources. Mothers spent on average about 4.5 h per day in the kitchen, where the
      strongest sources of magnetic field were located.

PMID- 9015810
TI  - Assessment of the exposure to biologically effective UV radiation using a
      dosimetric technique to evaluate the solar spectrum.
AB  - A cost-effective method employing polysulphone, nalidixic acid, 8-methoxypsoralen
      and phenothiazine as UV dosimeters is presented for evaluating the UV spectrum.
      The exposure measured by each dosimeter is a function of the source spectrum and
      the spectral response of the material. Each material has a different spectral
      response and records a different dose for the same exposure. A least squares
      method is employed to extract the source spectrum from the four dose
      measurements. A number of spectra have been evaluated, and the differences
      between these spectra and the associated irradiances, compared to the spectra and
      irradiances measured with a calibrated spectroradiometer is less than 20%. The
      technique allows simultaneous multisite measurement at positions that may be
      inaccessible to sensitive and expensive equipment. The technique was employed to
      evaluate the spectrum on the chest and shoulder of four subjects. The erythemal
      exposures were derived from the evaluated spectra with the chest exposures 0.7 to
      0.8 those of the shoulder exposures.

PMID- 9015811
TI  - Monte Carlo calculated stopping-power ratios, water/air, for clinical proton
      dosimetry (50-250 MeV).
AB  - Calculations of stopping power ratios, water to air, for the determination of
      absorbed dose to water in clinical proton beams using ionization chamber
      measurements have been undertaken using the Monte Carlo method. A computer code
      to simulate the transport of protons in water (PETRA) has been used to calculate
      sw.air-data under different degrees of complexity, ranging from values based on
      primary protons only to data including secondary electrons and high-energy
      secondary protons produced in nonelastic nuclear collisions. All numerical data
      are based on ICRU 49 proton stopping powers. Calculations using primary protons
      have been compared to the simple continuous slowing-down approximation (c.s.d.a.)
      analytical technique used in proton dosimetry protocols, not finding significant
      differences that justify elaborate Monte Carlo simulations except beyond the mean
      range of the protons (the far side of the Bragg peak). The influence of nuclear
      nonelastic processes, through the detailed generation and transport of secondary
      protons, on the calculated stopping-power ratios has been found to be negligible.
      The effect of alpha particles has also been analysed, finding differences smaller
      than 0.1% from the results excluding them. Discrepancies of up to 0.6% in the
      plateau region have been found, however, when the production and transport of
      secondary electrons are taken into account. The large influence of nonelastic
      nuclear interactions on proton depth-dose distributions shows that the removal of
      primary protons from the incident beam decreases the peak-to-plateau ratio by a
      large factor, up to 40% at 250 MeV. It is therefore emphasized that nonelastic
      nuclear reactions should be included in Monte Carlo simulations of proton beam
      depth-dose distributions.

PMID- 9015812
TI  - Optimizing the movement of a single absorber for 1D non-uniform dose delivery by
      (fast) simulated annealing.
AB  - A new simplified technique for 1D non-uniform dose delivery using a single
      dynamic absorber, driven by a computer system, has been recently proposed
      together with a simple analytic algorithm. This technique uses an optimized
      'stepped' absorber's speed profile and the generated fluence profile is an
      approximation of the desired radiation beam. In the case of non-uniform beam
      profiles with multiple maxima/minima, the original proposed 'stepping algorithm'
      has some limitations and produces a too rough approximation of the desired
      profiles. In order to increase the agreement between desired and generated
      profiles, more sophisticated optimization schemes are required. In this paper we
      have applied a variant of simulated annealing (SA) as a statistical optimization
      algorithm to further investigate the possibilities and the limits of the single
      absorber technique in the field of 1D intensity modulation. In the current
      application the cost function used is the mean square root of the percentage
      differences between desired and generated profiles, the absorber's resting times
      have been chosen as optimization variables and at each iteration just one
      variable is randomly changed, adding an incremental 'grain'. A Cauchy generating
      function is used, different cooling schedules are evaluated; constraints related
      to our apparatus are introduced and starting annealing parameters are set after
      some initial optimization tests. The method is tested in reproducing theoretical
      non-uniform beams, by comparing desired modulated fluence profiles with
      calculated fluence profiles obtainable with the single absorber after the
      derivation of optimized speed profiles by the proposed SA approach. The results
      of these simulations show that the application of the SA method optimizes the
      single absorber's performance and that clinically important modulated beams
      useful for conformal radiotherapy can be accurately reproduced.

PMID- 9015813
TI  - Adaptive radiation therapy.
AB  - Adaptive radiation therapy is a closed-loop radiation treatment process where the
      treatment plan can be modified using a systematic feedback of measurements.
      Adaptive radiation therapy intends to improve radiation treatment by
      systematically monitoring treatment variations and incorporating them to re
      optimize the treatment plan early on during the course of treatment. In this
      process, field margin and treatment dose can be routinely customized to each
      individual patient to achieve a safe dose escalation.

PMID- 9015814
TI  - General collection efficiency for liquid isooctane and tetramethylsilane used as
      sensitive media in a parallel-plate ionization chamber.
AB  - The general collection efficiency has been measured in liquid isooctane (C8H18)
      and tetramethylsilane (Si(CH3)4) used as the sensitive media in a parallel-plate
      ionization chamber, with an electrode distance of 1 mm, intended for photon and
      electron dosimetry applications. The liquid ionization chamber was irradiated at
      different dose rates by 140 keV photons from the decay of radioactive 99mTc. The
      measurements were made at potential differences of 50, 100, 200 and 500 V.
      Measurements were performed for each liquid and electric field strength, with the
      decay rate of 99mTc used as the dose-rate reference. The maximum dose rate was
      about 150 mGy min-1 in each experiment. When the measured general collection
      efficiency values are compared with the theoretical predictions for collection
      efficiency in gases, it is found that the latter also describe the general
      collection efficiency in the two liquids within 1% of the saturation current for
      collection efficiencies down to 60% when using experimentally determined
      recombination rate constants and on mobilities characteristic of each of the
      liquids.

PMID- 9015815
TI  - Equivalent methods to analyse dynamic experiments in which the input function is
      noisy.
AB  - A comparison is made between two methods of parameter estimation for analysis of
      dynamic experiments in which the input function is noisy. Noise in the input
      function leads to uncertainties in the calculated model-predicted values, and
      therefore the covariance matrix of the residuals is a function of the model
      parameters. Statistical uncertainties in the model-predicted values significantly
      change the nature of the fitting process and the quality of the results. The
      initial method uses a weighted least-squares criterion where the weighting matrix
      is the inverse of the full covariance matrix of the residuals, incorporating both
      the noise in the output data and the noise in the input function. The methodology
      was applied to dynamic emission tomography studies of the heart, where the blood
      (input) and tissue (output) tracer concentrations at each time are derived from
      two regions of interest in the same tomographic section. The second method
      introduces additional parameters to describe the input function, and adds terms
      to the weighted sum of squares which comprise the criterion. Instead of only
      summing the weighted terms to account for differences between the model and the
      output function, there is a second set of terms to account for the differences
      between the model and the input function. The two methods have different
      theoretical bases and appear to optimize different criteria, but it is shown here
      that they are equivalent to one another. The criterion which they minimize is the
      same under certain matrix invertibility constraints, which must be satisfied to
      ensure the stability of either method.

PMID- 9015816
TI  - Scatter rejection by air gaps in diagnostic radiology. Calculations using a Monte
      Carlo collision density method and consideration of molecular interference in
      coherent scattering.
AB  - The air gap technique is an old method for scatter rejection. It is still used in
      lung examinations and may be reconsidered for use in digital radiography. Using
      magnification techniques, for example in mammography, the air gap thereby
      introduced simultaneously yields scatter rejection. A Monte Carlo collision
      density method is exploited to investigate the physical parameters relevant to
      this technique. Radiation quantities of scattered photons at points behind a
      water slab both on and laterally displaced from the central axis are calculated
      and their dependence on field area, slab thickness, air gap length and detector
      type is derived. Values of 'scatter-to-primary' ratios of the plane energy
      fluence (the energy imparted to a totally absorbing detector) are given for
      perpendicularly incident 30, 70 and 130 kV energy spectra, slab thicknesses of
      0.05 and 0.2 m (30 kV: 0.05 m), air gaps of length 0.002-1.0 m and field areas
      from 8 x 10(-5) to 0.3 m2. Contrast degradation factors are derived for both
      totally absorbing and thin detectors. The influence on the scatter-to-primary
      ratios of using divergent instead of parallel beams and of neglecting molecular
      interference in coherent scattering is analysed.

PMID- 9015817
TI  - Characterization of post mortem arterial tissue using time-resolved photoacoustic
      spectroscopy at 436, 461 and 532 nm.
AB  - Time-resolved photoacoustic spectroscopy has been used to characterize post
      mortem arterial tissue for the purpose of discriminating between normal and
      atheromatous areas of tissue. Ultrasonic thermoelastic waves were generated in
      post mortem human aorta by the absorption of nanosecond laser pulses at 436, 461
      and 532 nm produced by a frequency doubled Q-switched Nd:YAG laser in conjunction
      with a gas filled Raman cell. A PVDF membrane hydrophone was used to detect the
      thermoelastic waves. At 436 nm, differences in the photoacoustic signatures of
      normal tissue and atherorma were found to be highly variable. At 461 nm, there
      was a clear and reproducible difference between the photacoustic response of
      atheroma and normal tissue as a result of increased optical attenuation in
      atheroma. At 532 nm, the generation of subsurface thermoelastic waves provided a
      means of determining the structure and thickness of the tissue sample. It is
      suggested that pulsed photoacoustic spectroscopy at 461 and 532 nm may find
      application in characterizing arterial tissue in situ by providing information
      about both the composition and thickness of the vessel wall.

PMID- 9015818
TI  - A quantitative comparison of some FADS methods in renal dynamic studies using
      simulated and phantom data.
AB  - Simulated and phantom data were used to determine if factor analysis of dynamic
      structures (FADS) methods can be used quantitatively. FADS methods tested
      included variants of apex seeking, the intersection method, cluster analysis and
      spatial constraints. These were compared with a region-of-interest (ROI)
      approach. Simulated renal studies were prepared using from three to six
      homogeneous structures. These corresponded to two blood background structures;
      two structures (one pathological) for parenchyma; and two structures (one
      pathological) for the collecting system. Time-activity curves for background,
      parenchyma and collecting system were obtained for each method and compared with
      the true curve. A kidney phantom was modelled using a tunnelled vessel filled
      with chelating material A variable flow was controlled by a peristaltic pump
      representing the renal filtration of fluid. The glomerular filtration rate (GFR)
      was estimated using FADS and ROI-based methods and compared with the values
      measured experimentally. Most FADS methods perform well in the absence of
      pathology, but less well than the ROI-based method when pathology is present.
      Some FADS methods perform better than the ROI-based method when background
      estimation is a problem as in the GFR experiment. For quantitative analysis, the
      success of FADS depends on the validity of the underlying assumptions and on the
      appropriate nature of the constraints.

PMID- 9015819
TI  - A comparison of radiation dose measured in CT dosimetry phantoms with
      calculations using EGS4 and voxel-based computational models.
AB  - CT is a high-dose examination and possibly the dominant contributor to dose from
      diagnostic radiology. Estimates of organ doses are obtained from Monte Carlo
      calculations and used to quantify radiation risk. To ensure the validity of using
      Monte Carlo calculations to estimate actual dose, measurements must be compared
      with calculations. We have measured doses to CT head and chest dosimetry phantoms
      and compared them with Monte Carlo (EGS4) calculated doses in voxel-based
      computational models of the phantoms. The simulation used an x-ray spectrum
      calculated from the specified values of the scanner's x-ray tube parameters. The
      scanner's beam-shaping filter was included in the modelling. Measured and
      calculated doses to both the head and chest phantoms agreed to within 7%. The
      inclusion of Rayleigh scattering in the calculations has a significant effect if
      only one slice is scanned but not if multiple slices are scanned.

PMID- 9015820
TI  - The local noise property in positron volume imaging and optimal conditions for
      the signal-to-noise ratio of the 3D reconstructed image.
AB  - The local noise property of a 3D PET reconstructed image is investigated for a
      uniform-activity sphere distributed in a constantly attenuating spherical object.
      The positional dependence of the statistical noise is approximately derived and
      calculated for some special cases. It is suggested that a larger diameter of the
      activity sphere causes noise amplification, and the noise property for the large
      attenuating sphere is close to that for a non-attenuating object with the same
      total number of measuring counts. By considering noise propagation of two
      spherical activity distributions, we suggest that the signal-to-noise ratio of
      the image depends on a set of projection directions and the sizes and intensities
      of the activity distributions. In a simple case, we derive an optimal value of
      the maximum acceptance angle for the projection directions to improve the signal
      to-noise ratio of the image.

PMID- 9015821
TI  - Hyperaemia evaluation in clinical diathermy by four-electrode impedance
      measurements.
AB  - The four-electrode electrical impedance measurement technique is proposed for the
      evaluation of the hyperaemia variation in tissues treated by diathermic therapy.
      An impedance meter suitable for such measurements is described, and an electrical
      model of the heated tissues, concerning the impedance variation during diathermy
      and its relation with hyperaemia, is presented. The occurrence of the substantial
      contribution of blood to the overall transverse impedance is demonstrated by
      comparing the experimental results with those arising from a 2D
      electrical/thermal model of the treated tissues. A two-admittance model is
      proposed to explain the electrical behaviour of the tissues treated by diathermy.
      The model allows us to separate the impedance violation due to the temperature
      dependence of tissue conductivity from that due to the change of tissue blood
      content. The results of preliminary measurements of tissue impedance on healthy
      volunteers treated by electromagnetic diathermy are presented and discussed,
      showing the feasibility of impedance detection of hyperaemia variations inside
      tissues.

PMID- 9015822
TI  - The role of the piriform cortex in kindling.
AB  - In epilepsy research, there is growing interest in the role of the piriform
      cortex (PC) in the development and maintenance of limbic kindling and other types
      of limbic epileptogenesis leading to complex partial seizures, i.e. the most
      common type of seizures in human epilepsy. The PC ("primary olfactory cortex") is
      the largest area of the mammalian olfactory cortex and receives direct
      projections from the olfactory bulb via the lateral olfactory tract (LOT). Beside
      the obvious involvement in olfactory perception and discrimination, the PC,
      because of its unique intrinsic associative fiber system and its various
      connections to and from other limbic nuclei, has been implicated in the study of
      memory processing, spread of excitatory waves, and in the study of brain
      disorders such as epilepsy with particular emphasis on the kindling model of
      temporal lobe epilepsy with complex partial seizures. The interest in the
      kindling model is based primarily on the following observations. (1) The PC
      contains the most susceptible neural circuits of all forebrain regions for
      electrical (or chemical) induction of limbic seizures. (2) During electrical
      stimulation of other limbic brain regions, broad and large afterdischarges can be
      observed in the ipsilateral PC, indicating that the PC is activated early during
      the kindling process. (3) The interictal discharge, which many consider to be the
      hallmark of epilepsy, originates in the PC, independent of which structure serves
      as the kindled focus. (4) Autoradiographic studies of cerebral metabolism in rat
      amygdala kindling show that, during focal seizures, the area which exhibits the
      most consistent increase in glucose utilization is the ipsilateral paleocortex,
      particularly the PC. (5) During the commonly short initial afterdischarges
      induced by stimulation of the amygdala at the early stages of kindling, the PC is
      the first region that exhibits induction of immediate-early genes, such as c-fos.
      (6) The PC is the most sensitive brain structure to brain damage by continuous or
      frequent stimulation of the amygdala or hippocampus. (7) Amygdala kindling leads
      to a circumscribed loss of GABAergic neurons in the ipsilateral PC, which is
      likely to explain the increase in excitability of PC pyramidal neurons during
      kindling. (8) Kindling of the amygdala or hippocampus induces astrogliosis in the
      PC, indicating neuronal death in this brain region. Furthermore, activation of
      microglia is seen in the PC after amygdala kindling. (9) Complete bilateral
      lesions of the PC block the generalization of seizures upon kindling from the
      hippocampus or olfactory bulb. Incomplete or unilateral lesions are less
      effective in this regard, but large unilateral lesions of the PC and adjacent
      endopiriform nucleus markedly increase the threshold for induction of focal
      seizures from stimulation of the basolateral amygdala (BLA) prior to and after
      kindling, indicating that the PC critically contributes to regulation of
      excitability in the amygdala. (10) Potentiation of GABAergic neurotransmission in
      the PC markedly increases the threshold for induction of kindled seizures via
      stimulation of the BLA, again indicating a critical role of the PC in regulation
      of seizure susceptibility of the amygdala. Microinjections of NMDA antagonists or
      sodium channel blockers into the PC block seizure generalization during kindling
      development. (11) Neurophysiological studies on the amygdala-PC slice preparation
      from kindled rats showed that kindling of the amygdala induces long-lasting
      changes in synaptic efficacy in the ipsilateral PC, including spontaneous
      discharges and enhanced susceptibility to evoked burst responses. The
      epileptiform potentials in PC slice preparations from kindled rats seem to
      originate in neuron at the deep boundary of PC. Spontaneous firing and enhanced
      excitability of PC neurons in response to kindling from other sites is also seen
      in vivo, substantiating the fact that kindling induces long-lasting changes in
      the PC c

PMID- 9015823
TI  - Implication of ATP receptors in brain functions.
AB  - The possible implication of P2-purinoceptors in brain functions is reviewed.
      Involvement of P2-purinoceptors in memory and learning (Section 2) is suggested
      by ATP release from hippocampal slices [Wieraszko, A., Goldsmith, G. and
      Seyfried, T. N. (1989) Brain Res. 485, 244-250], induction of fast synaptic
      currents in cultured hippocampal neurons [Inoue, K., Nakazawa, K., Fujimori, W.
      and Takanaka, A. (1992a) Neurosci. Lett. 134, 294-299] and long-lasting
      enhancement of the population spikes [Wieraszko, A. and Seyfried, T. N. (1989)
      Brain Res. 491, 356-359; Nishimura, S., Mohri, M., Okada, Y. and Mori, M. (1990)
      Brain Res. 525, 165-169; Fujii, S., Kato, H., Furuse, H., Ito, K., Osada, H.,
      Hamaguchi, T. and Kuroda, Y. (1995) Neurosci, Lett. 187, 130-132], as well as ATP
      release on glutamate stimulation to evoke an increase in intracellular Ca2+ in
      hippocampal cells [Inoue, K., Koizum, S. and Nakazawa, K. (1995) NeuroReport 6,
      437-440]. Moreover, mRNAs for certain types of P2x-purinoceptors are present in
      the hippocampus [Collo, G., North, R. A., Kawashima, E., Merlo-Pich, E.,
      Neidhart, S., Surprenant, A. and Buell, G. (1996) J. Neurosci. 16, 2495-2507]. It
      is likely, therefore, that ATP may be involved in modulation of synaptic
      efficiency in the hippocampus. The implication of ATP in schizophrenia is
      suggested by the fact that antipsychotic drugs inhibit ATP-evoked responses in
      PC12 cells [Koizumi, S., Ikeda, M., Nakazawa, K., Inoue, K., Ito, K. and Inoue,
      K. (1995b) Biochem. Biophys. Res. Commun. 210, 624-630] without blocking the
      action of dopamine D2 receptors. Involvement of P2-purinoceptors in Sections 4
      ("Pain and cognition") and 5 ("Central regulation of the autonomic system") are
      also discussed.

PMID- 9015824
TI  - Alterations in apolipoprotein E expression during aging and neurodegeneration.
AB  - Apolipoprotein E (apoE) is a 34 kDa protein that plays an important role in
      cholesterol transport, uptake and redistribution. Within the nervous system, apoE
      might be involved in maintaining synaptic integrity after injury and during
      aging. ApoE might help maintain the integrity of the synaptodendritic complex by
      several different mechanisms. Among them, recent studies have suggested that
      apoE: (1) stabilizes the neuronal cytoskeleton; (2) plays an important role in
      transporting esterified cholesterol to neurons undergoing reinnervation where it
      is taken up by the low density lipoprotein receptor-related protein pathway and
      used as a precursor for the synthesis of new synaptic terminals; (3) regulates
      interactions between neurons and the extracellular matrix (e.g. laminin); and (4)
      regulates levels of intracellular calcium. The main objective of the manuscript
      is to review the current progress in understanding the functions of apoE in the
      nervous system and how malfunctioning of this molecule might result in
      neurodegenerative disorders such as Alzheimer's disease.

PMID- 9015825
TI  - Autonomic neuromuscular transmission at a varicosity.
AB  - This review attempts to clarify the definition of what constitutes an autonomic
      neuromuscular function formed by a varicosity. Ultrastructural studies of serial
      sections through varicosities, partly or wholly bare of Schwann cell covering,
      show that areas of close apposition occur between varicosities and muscle cell
      membrane that vary between 20 and 150 nm, depending on the muscle considered.
      Consideration of the diffusion of purine transmitters and their receptor kinetics
      after secretion in a packet show that the number of purinergic receptor channels
      opened at a site of 150 nm apposition by a varicosity is about 15% of that at a
      site of 50 nm apposition. These results, together with the analysis of the
      stochastic fast component and the deterministic slow components of the rising
      phase of the EJP suggest that the stochastic fast component is due to
      varicosities that form especially close appositions (20-50 nm), whereas the
      deterministic slow component is due to the large number of varicosities at
      distances up to about 150 nm. Varicosities forming appositions of 20-150 nm with
      muscle cells several hundred micrometers long possess junctional receptor types
      distinct from extrajunctional receptors. According to this argument, then, there
      are two different classes of varicosities: one that gives rise to a relatively
      large junctional current and another that is responsible for a very small
      junctional current. Present evidence suggests that two subclasses of varicosities
      can be discerned amongst the varicosities that generate large junctional
      currents. One of these subclasses of varicosity possesses relatively few post
      junctional receptors compared with the amount of transmitter reaching the
      receptors from the varicosity, so that the junctional current generated is
      determined by the size of the receptor population; in this case, the size of the
      transmitter packages released from these varicosities is unknown and the size of
      the junctional current is relatively constant. The other subclass of varicosity
      possesses large receptor patches, sufficient to accommodate the largest amounts
      of transmitter released from the varicosities: in this case, the size of the
      transmitter packages is shown to be highly non-uniform. These speculations await
      confirmation by direct labelling of the receptor patches beneath varicosities, a
      possibility that is likely to be realized in the near future.

PMID- 9015826
TI  - Neural plasticity in cerebellar cultures.
AB  - Cerebellar granule cells and oligodendrocytes are destroyed and astrocytes are
      functionally compromised by exposure of organotypic cerebellar cultures derived
      from newborn mice to cytosine arabinoside for the first 5 days in vitro.
      Consequently, myelin does not form and Purkinje cells survive in increased
      numbers, but without astrocytic ensheathment. In the absence of glial sheaths,
      Purkinje cells have altered membrane properties and reduced input resistance.
      Their inhibitory recurrent axon collaterals sprout enormously and hyperinnervate
      the unensheathed somata of other Purkinje cells and form heterotypical synapses
      with Purkinje cell dendritic spines normally occupied by homotypical excitatory
      parallel fiber (granule cell axon) terminals. This reorganization of the cortical
      circuitry, in which recurrent axon collaterals are the dominant inhibitory
      elements, allows retention of some inhibition in the absence of parallel fiber
      excitation of the inhibitory interneurons. In the absence of neuronal activity,
      the full complement of inhibitory synapses is not developed and the cultures
      exhibit sustained cortical hyperactivity after recovery from the blockade. If
      granule cells and glia are replaced, a second round of reorganization ensues, in
      the direction of restoration of the normal cortical circuitry. The cultures are
      myelinated and the number of recurrent axon collaterals is reduced. Astrocytes
      ensheath Purkinje cell somata and strip excess axosomatic synapses, as well as
      eliminate some of the heterotypical synapses in the cortical neuropil. Parallel
      fibers synapse with already present Purkinje cell dendritic spines and with newly
      proliferated spines, the latter induced by an astrocyte secreted factor. As
      homotypical synapses develop and heterotypical synapses decline, Purkinje cells
      undergo apoptosis and their population is reduced to control levels. With the
      restoration of parallel fiber excitation, recurrent axon collaterals are no
      longer the dominant cortical inhibitory elements. If neuronal activity is blocked
      as the granule cells and glia are replaced, there is incomplete formation of
      inhibitory synapses, and cortical discharges are hyperactive after recovery from
      activity blockade.

PMID- 9015828
TI  - Platelet-activating factor in the CNS.
AB  - Platelet-activating factor (PAF) is a phospholipid synthesized in a variety of
      cells throughout the body. Platelet-activating factor has been identified in the
      CNS and has a number of diverse physiological and pathological functions. It has
      been shown to be a modulator of many CNS processes, ranging from long-term
      potentiation (LTP) to neuronal differentiation. Excessive levels of PAF appear to
      play an important role in neuronal cell injury, such as that resulting from
      ischaemia, inflammation, human immunodeficiency syndrome (HIV) and meningitis.
      The beneficial effects of PAF receptor antagonists are many and give rise to
      possible therapeutic strategies for neurotrauma.

PMID- 9015827
TI  - Dynorphin and epilepsy.
AB  - Studies on dynorphin involvement in epilepsy are summarised in this review.
      Electrophysiological, biochemical and pharmacological data support the hypothesis
      that dynorphin is implicated in specific types of seizures. There is clear
      evidence that this is true for complex partial (limbic) seizures, i.e. those
      characteristic of temporal lobe epilepsy, because; (1) dynorphin is highly
      expressed in various parts of the limbic system, and particularly in the granule
      cells of the hippocampus; (2) dynorphin appears to be released in the hippocampus
      (and in other brain areas) during complex partial seizures; (3) released
      dynorphin inhibits excitatory neurotransmission at multiple synapses in the
      hippocampus via activation of kappa opioid receptors; (4) kappa opioid receptor
      agonists are highly effective against limbic seizures. Data on generalised tonic
      clonic seizures are less straightforward. Dynorphin release appears to occur
      after ECS seizures and kappa agonists exert a clear anticonvulsant effect in this
      model. However, more uncertain biochemical data and lack of efficacy of kappa
      agonists in other generalised tonic-clonic seizure models argue that the
      involvement of dynorphin in this seizure type may not be paramount. Finally, an
      involvement of dynorphin in generalised absence seizures appears unlikely on the
      basis of available data. This may not be surprising, given the presumed origin of
      absence seizures in alterations of the thalamo-cortical circuit and the low
      representation of dynorphin in the thalamus. In conclusion, it may be suggested
      that dynorphin plays a role as an endogenous anticonvulsant in complex partial
      seizures and in some cases of tonic-clonic seizures, but most likely not in
      generalised absence. This pattern of effects may coincide with the antiseizure
      spectrum of selective kappa agonists.

PMID- 9015829
TI  - Development of fetal hippocampal grafts in intact and lesioned hippocampus.
AB  - Functional recovery observed in Parkinson's disease patients following grafting
      of fetal substantia nigra has encouraged the development of similar grafting
      therapy for other neurological disorders. Fetal hippocampal grafting paradigms
      are of considerable significance because of their potential to treat neurological
      disorders affecting primarily hippocampus, including temporal lobe epilepsy,
      cerebral ischemia, stroke, and head injury. Since many recent studies of
      hippocampal transplants were carried out with an aim of laying the foundation for
      future clinical applications, an overview of the development of fetal hippocampal
      transplants, and their capability for inducing functional recovery under
      different host conditions is timely. In this review, we will summarize recent
      developments in hippocampal transplants, especially the anatomical and/or
      functional integration of grafts within the host brain under specific host
      conditions, including a comparison of intact hippocampus with various types of
      hippocampal lesions or injury. Improvements in grafting techniques, methods for
      analysis of graft integration and graft function will be summarized, in addition
      to critical factors which enhance the survival and integration of grafted cells
      and alternative sources of donor cells currently being tested or considered for
      hippocampal transplantation. Viewed collectively, hippocampal grafting studies
      show that fetal hippocampal tissue/cells survive grafting, establish both
      afferent and efferent connections with the host brain, and are also capable of
      ameliorating certain learning and memory deficits in some models. However, the
      efficacy of intracerebral fetal hippocampal grafts varies considerably in
      different animal models, depending on several factors: the mode of donor tissue
      preparation, the method of grafting, the state of host hippocampus at the time of
      grafting, and the placement of grafts within the hippocampus. Functional
      improvement in many models appeared to be caused partially by re-establishment of
      damaged circuitry and partially by a trophic action of grafts. However, exact
      mechanisms of graft-mediated behavioral recovery remain to be clarified due to
      the lack of correlative analysis in the same animal between the degree of graft
      integration and behavioral recovery. Issues of mechanisms of action, degree of
      restoration of host circuitry and amelioration of host pathological conditions
      will need to be sorted out clearly prior to clinical use of fetal hippocampal
      transplants for susceptible neurological conditions.

PMID- 9015861
TI  - Functional reconstitution of detergent-solubilized bovine calf testis luteinizing
      hormone/chorionic gonadotropin receptor into phospholipid vesicles.
AB  - An LH/CG receptor-enriched fraction was prepared by ultrafiltration of sucrose
      density gradient-purified light membranes derived from bovine calf testicular
      homogenates and solubilized with Triton X-100. To confirm the functional nature
      of the detergent-solubilized LH/CG receptor, the extract was first incorporated
      by lipid hydration into phospholipid vesicles composed of dioleoyl
      phosphatidylcholine and cholesterol, 2:1 molar ratio. LH/CG receptor
      incorporation was then determined by measurement of specific binding of
      [125I]hCG. Specific binding of [125I]hCG by the reconstituted receptor was
      saturable, time-dependent, and thermally stable at room temperature. Scatchard
      analysis of competitive binding data indicated the presence of a single class of
      high-affinity (6.9 x 10(10)M-1), low-capacity (17.5 fmol hCG/mg protein) binding
      sites. The reconstituted receptor was functionally coupled to adenylyl cyclase
      and responded to both LH and NaF with increased cyclic AMP (cAMP) production.
      Stimulation of LH/CG receptor-enriched proteoliposomes with LH resulted in
      concentration-dependent uptake of external calcium (as 45Ca2+), which was hormone
      specific, saturable, and sensitive to blockade by voltage-dependent and voltage
      independent calcium channel antagonists. Similar uptake could not be induced by
      sodium fluoride, (Bu)2 cAMP, GTP-gamma-S, cholera toxin, or pertussis toxin.
      These results indicate that the reconstituted LH/CG receptor, as is the membrane
      associated receptor, is functionally coupled to signal transduction pathways
      involving both adenylyl cyclase activation and calcium mobilization, and is a
      reliable working model that will facilitate further examination of the molecular
      mechanisms of LH action.

PMID- 9015862
TI  - Induction of granulocytic differentiation in myeloblasts by 17-beta-estradiol
      involves the leukotriene D4 receptor.
AB  - 17-beta-Estradiol (beta E) causes granulocytic differentiation and neutrophilia
      in mice. However, the presence of estrogen receptors in myeloblasts and
      granulocytic progenitor cells has not been reported. beta E can be converted to a
      bioreactive species, estradiolquinone. We have previously shown that hydroquinone
      (HQ), via conversion to bioreactive p-benzoquinone (BQ), causes neutrophilia in
      mice and induces granulocytic differentiation in myeloblasts through interaction
      with the leukotriene D4 (LTD4) receptor. Therefore, we tested whether beta E
      could be oxidized by a myeloperoxidase-mediated reaction to a bioreactive
      intermediate, which might, in turn, induce granulocytic differentiation in mouse
      myeloblasts by activating the LTD4 receptor, thus obviating the need for LTD4,
      the downstream intracellular mediator of granulocyte colony-stimulating factor (G
      CSF)-induced signal transduction. The interleukin (IL)-3-dependent, G-CSF
      inducible normal mouse myeloblastic cell line, 32D cl 3(G), was used to determine
      the ability of beta E to induce terminal granulocytic differentiation in
      myeloblasts. Morphological analysis of stage-specific granulocytic
      differentiation indicated that beta E was capable of the concentration- (10(-8)
      10(-4)M) and time-(6d) dependent induction of a complete program of terminal
      granulocytic differentiation in myeloblasts similar to that seen with G-CSF or
      LTD4. beta E-induced granulocytic differentiation was prevented by the peroxidase
      inhibitor, indomethacin, and was completely and competitively inhibited in the
      presence of a specific LTD4 receptor antagonist, MK-571, suggesting that a
      bioreactive form of estradiol, such as estradiolquinone, is interacting with the
      receptor. beta E was shown to cause a similar concentration-dependent induction
      of granulocytic differentiation in human HL-60 myeloblasts that was also
      inhibited by the receptor antagonist. Biological effects of beta E in nontarget
      tissues may result from the interaction of bioreactive estradiolquinone with
      critical cellular macromolecules involved in normal cellular signaling pathways.

PMID- 9015863
TI  - Phosphoinositide-dependent in vitro phosphorylation of profilin by protein kinase
      C. Phospholipid specificity and localization of the phosphorylation site.
AB  - Phosphoinositides bind to profilin and regulate actin-based cytoskeletal protein
      assembly. We report here that profilin is phosphorylated in vitro by protein
      kinase C (PKC) in the presence of phosphoinositides and micromolar concentrations
      of calcium. PKC-mediated phosphorylation of profilin was observed only in the
      presence of phosphoinositides; phosphatidylserine and diacylglycerol (known
      activators of PKC) and other lipids, including phosphatidic acid and
      phosphatidylglycerol phosphate, did not activate the phosphorylation. The
      activation of PKC-mediated phosphorylation of profilin by phosphoinositides was
      as follows: phosphatidylinositol (PI) 4-phosphate (K(m) = 18 microM) > PI 4,5
      bisphosphate (K(m) = 30 microM) > PI (no activation). About 0.5 mol phosphate was
      incorporated per mol of profilin. Phosphorylation of profilin by PKC was not
      affected by the presence of various concentrations of actin. Phospho-amino acid
      analysis showed serine to be the only amino acid phosphorylated. The amino acid
      sequence of a phosphopeptide from CNBr-digested profilin corresponded to the COOH
      terminal peptide of profilin (Ala-Ser-His-Leu-Arg-Ser-Gln-Tyr). Further digestion
      of this phosphopeptide by trypsin generated two phosphopeptides (Arg-Ser-Gln-Tyr
      and Ser-Gln-Tyr), thereby confirming that the phosphorylation site was the
      antepenultimate Ser (Ala-Ser-His-Leu-Arg-Arg-Ser(P)-Gln-Tyr).

PMID- 9015864
TI  - Protein kinase C inhibits the Ca(2+)-dependent stimulation of phospholipase C
      beta 1 in vitro.
AB  - Protein kinase C (PKC) inhibited the Ca(2+)-dependent stimulation of a 600-fold
      purified phospholipase C beta 1 (PLC-beta 1). Inhibition by PKC was time
      dependent, and required ATP and diacylglycerol. Inhibition was more pronounced
      when the PLC assay was conducted with a PIP2 substrate mixture containing
      phosphatidylserine, then with a substrate mixture containing phosphatidyle
      thanolamine. Cyclic AMP-dependent protein kinase A did not inhibit PLC-beta 1
      activity. PKC did not affect the rate of PLC-beta 1 activation by Ca2+ or the
      rate of PLC-beta 1 deactivation by EGTA. PLC-beta 1 purified 1700-fold was less
      sensitive to inhibition by PKC despite stoichiometric phosphorylation. These
      results demonstrate that PKC inhibits the Ca(2+)-dependent stimulation of a 600
      fold purified PLC-beta 1 in vitro. Furthermore, purification of PLC-beta 1 to
      homogeneity results in a diminished sensitivity to inhibition by PKC, indicating
      that other components may participate in mediating the effect of PKC on the
      Ca(2+)-dependent stimulation of PLC-beta 1 in vitro.

PMID- 9015865
TI  - Heterologous desensitization of the human endothelin A and neurokinin A receptors
      in Xenopus laevis oocytes.
AB  - Endothelin 1 (ET1) desensitizes endothelin A receptor for 90-110 min while
      neurokinin A (NKA) desensitizes neurokinin A receptor for 25-35 min in Xenopus
      laevis oocytes. In the present study, endothelin A receptor and neurokinin A
      receptor were coexpressed in Xenopus laevis oocytes in an effort to characterize
      heterologous desensitization of the receptors that activate phospholipase C-beta.
      ET1 desensitizes both the endothelin A receptor and the neurokinin A receptor for
      90-110 min, whereas stimulation with NKA desensitizes the same two receptors for
      only 25-35 min. Homologous and heterologous desensitization experiments were also
      carried out with endothelin 3 (ET3), a ligand that exhibits lower affinity to the
      endothelin A receptor and a quicker dissociation rate than ET1. ET3 was unable to
      desensitize endothelin A receptor and the neurokinin A receptor; this is in
      contrast to ET1 that desensitizes both receptors. These results suggests that the
      receptors that undergo homologous desensitization are able to heterologously
      desensitize other receptors that activate PLC-beta. Furthermore, the agonist
      specific dissociation constant dictates the extent of desensitization and time of
      recovery of the receptor-mediated response.

PMID- 9015867
TI  - Practitioner provision of preventive care in general practice consultations:
      association with patient educational and occupational status.
AB  - Socio-economically disadvantaged individuals experience significantly greater
      mortality and morbidity relative to advantaged individuals. General practitioners
      have been suggested to occupy a position which has the capacity to ameliorate the
      health consequences of socio-economic disadvantage. Community studies of
      preventive care status suggest, however, that socio-economically disadvantaged
      individuals are less likely to receive appropriate preventive care. Using a
      convenience sample of 22 general practitioners, 579 consultations were audiotaped
      to determine whether practitioner provision of preventive care was associated
      with the educational and occupational status of patients. Practitioner provision
      of preventive care was assessed in terms of: the proportion of consultations in
      which discussion of at least one preventive care topic occurred; the number of
      preventive care topics discussed; and the proportion of consultations in which
      each of six specific preventive care topic were discussed. Practitioners were
      significantly less likely to discuss at least one preventive care topic with
      patients of high occupational status. No significant differences were observed
      between patient groups in the number of preventive care topics, discussed, and in
      the likelihood of receiving preventive care discussion concerning each of six
      preventive topics. However, a consistent trend of practitioners being less likely
      to discuss preventive care topics with patients of high educational or
      occupational status was evident for all outcome variables. The pattern of results
      suggests that previously reported findings of socio-economically disadvantaged
      individuals having a poorer preventive care status may not be attributable to
      differentials in practitioner's provision of preventive care. Greater attention
      should therefore be given to identifying and resolving barriers other than
      practitioner-based barriers to preventive care provision if these differentials
      in preventive care status are to be reduced.

PMID- 9015866
TI  - Lack of constitutive activation or inactivation of the platelet-activating factor
      receptor by glutamate substitution of alanine 230.
AB  - The platelet-activating factor (PAF) receptor (PAFR) is a G protein-coupled
      receptor (GPCR) that mediates a diverse array of biological responses to PAF.
      Recently, we provided evidence that the third intracellular domain (3i) of the
      rat PAFR (rPAFR) is a critical determinant in its coupling to phosphoinositide
      phospholipase C (PI PLC)-activating G proteins. In the present study, we assessed
      the potential role of a conserved alanine in the carboxyl-terminal region of 3i
      of the rPAFR in rPAFR signaling activity. Previous studies with the m5 muscarinic
      acetylcholine and human PAF receptors revealed that substitution of a carboxyl
      terminal alanine was found to impair receptor-mediated PI PLC activation. Here we
      report the effects of the analogous nonconservative substitution of glutamate for
      alanine 230 of the rPAFR (rPAFR A230E) on receptor-mediated agonist binding and
      PI PLC activation following transient expression of the receptor cDNA. BHK cells
      transfected with a cDNA encoding the rPAFR A230E exhibited PAF-stimulated
      increases in inositol phosphate (IP) accumulation with no increase in basal
      levels of IPs. PAF-stimulated IP production in rPAFR transfectants was dependent
      on the amount of DNA transfected, although PAF provoked a larger increase in IPs
      in rPAFR transfectants than in rPAFRA230E transfectants in cells transfected with
      equal amounts of receptor cDNA. This latter finding apparently reflects
      differences in the transfection efficiency or expression of the wild-type and
      rPAFR A230E cDNAs because PAF produced indistinguishable effects on IP
      accumulation in rPAFR and rPAFR A230E transfectants expressing equivalent numbers
      of receptors. These results provide evidence for a nonconserved role of this
      conserved alanine in coupling of group I GPCRs to PI PLC-activating G proteins
      and also suggest that this residue has differential roles in regulating
      expression and signaling by rat and human PAFRs.

PMID- 9015868
TI  - Nurse staffing patterns and hospital efficiency in the United States.
AB  - The objective of this exploratory study was to assess the effects of four nurse
      staffing patterns on the efficiency of patient care delivery in the hospital:
      registered nurses (RNs) from temporary agencies; part-time career RNs; RN rich
      skill mix; and organizationally experienced RNs. Using Transaction Cost Analysis,
      four regression models were specified to consider the effect of these staffing
      plans on personnel and benefit costs and on non-personnel operating costs. A
      number of additional variables were also included in the models to control for
      the effect of other organization and environmental determinants of hospital
      costs. Use of career part-time RNs and experienced staff reduced both personnel
      and benefit costs, as well as total non-personnel operating costs, while the use
      of temporary agencies for RNs increased non-personnel operating costs. An RN rich
      skill mix was not related to either measure of hospital costs. These findings
      provide partial support of the theory. Implications of our findings for future
      research on hospital management are discussed.

PMID- 9015869
TI  - Health expenditures in Latin America and the Caribbean.
AB  - This paper presents the results of a study commissioned by the Latin American and
      Caribbean Technical Department of the World Bank to document and analyze health
      expenditures in Latin America and the Caribbean. In 1990, the countries of this
      region spent US$ 69 billion on health, with an average per capita health
      expenditure of US$ 162. On average, the countries spent 6.2% of their GDP on
      health, with the expenditures divided about equally between the public and
      private sectors. In both the public and private sectors, per capita health
      expenditures were positively and significantly correlated with per capita income.
      However, this relationship holds only for the public sector, when health
      expenditures are measured as a proportion of GDP. While several poorer countries
      were dependent on external assistance, with increasing income, the countries
      relied more on public expenditures to finance health care. Based on the limited
      time series data, it is evident that there was a considerable variation among
      countries regarding the proportion spent on capital investments, primary health
      care, and drugs, but not on salaries. Looking ahead, with increasing economic
      development, the proportion of GDP spent on health, along with public health
      expenditure as a proportion of total health expenditure, is likely to increase
      rapidly, while aid dependency is likely to decline.

PMID- 9015870
TI  - Traditions and reproductive technology in an urbanizing north Indian village.
AB  - This article addresses the practices of prenatal sex determination and sex
      selective abortion through ethnographic research in Shahargaon, a Jat village
      undergoing rapid urbanization and cultural change in north India. The paper
      presents the sociodemographic outcomes of sex-selective abortion practiced within
      a system of patriarchy, manifested in terms of son preference and daughter
      disfavor. It argues that changes from an agriculture to an urban economy have led
      to a decrease in family size among Shahargaon Jats. In spite of improvements in
      educational and economic status, there is a reinforcement of son preference and
      daughter disfavor in the Jat community in Shahargaon. Jat couples are using
      prenatal sex determination and sex-selective abortion to achieve smaller family
      size and to reduce the number of daughters in a family.

PMID- 9015871
TI  - Suicide among foreign-born minorities and Native Swedes: an epidemiological
      follow-up study of a defined population.
AB  - The increasing number of immigrants in Sweden during the past four decades has
      brought the health of ethnic groups into focus. The purpose of this study was to
      analyse the influence of ethnicity, age, sex, marital status and date of
      immigration on suicide rates. The study population consisted of all individuals
      over 15 years of age, N = 6,725,274, from the Swedish census of 1985 and is based
      on individual data. Suicides and undetermined deaths, during the follow-up period
      1986-1989, were taken from the central Cause of Death Register. Ethnicity,
      defined as being foreign-born, was a risk factor for suicide for both men and
      women with risk ratios of 1.21 (1.11-1.31) and 1.36 (1.21-1.53), respectively,
      with control for age and marital status. Being unmarried was also a risk factor
      for both males and females with risk ratios from 1.26 to 5.55 in different age
      groups. The highest risk ratios for suicide in Sweden, adjusted for age, were
      found among males born in Russia and Finland. They also showed higher suicide
      risks than in their countries of birth. Females born in Hungary, Russia, Finland
      and Poland all had high risks of committing suicide in Sweden and they also had
      higher risks than in their countries of birth. Further, being of male sex, aged
      45-54 or 75 and older, and born in Eastern Europe or Finland were significant
      risk factors for suicide. The same was true for those who had immigrated to
      Sweden in 1967 or earlier and were born in Finland, Eastern Europe or in non
      European countries. These findings are of great importance for primary health
      care and psychiatric care planning.

PMID- 9015872
TI  - Long-term illness among indigenous and foreign-born people in Sweden.
AB  - This study shows the influence on self-reported health of ethnicity,
      operationalised as Swedes and foreign-born people from Finland, Western countries
      (Western Europe-except for Finland and South Europe-the United States, Canada,
      Australia, New Zealand and Japan), South Europe and all other countries (East
      Europe and non-European, non-Western countries). A simple random sample of 23.864
      Swedes and foreign-born people were interviewed in 1980-1981 and 1988-1989 by
      Statistics Sweden. In successive models starting with only ethnicity and age, one
      variable at a time was included in the two main models, one with material and
      economic factors and another with lifestyle factors as independent variables, in
      order to study how the importance of ethnicity changed. The age-adjusted
      relations between male and female Finns and severe long-term illness were reduced
      from an odds ratio of 2.37 and 1.86, respectively, to 1.90 and 1.70 after
      including educational status, marital status, exercise, smoking, and body mass
      index in the final model. The high odds ratios for males and females born in
      South Europe or born in non-Western countries decreased with the inclusion of
      lifestyle factors but were still high 2.26 and 2.50 in South Europeans and 1.94
      and 1.81 in non-Westerners. Males and females born in Finland, South Europe or in
      non-Western countries had high odds ratios for severe long-term illness when
      education, material standard, economic resources, leisure opportunities and
      social network were simultaneously controlled for. People born in Western
      countries showed no association to limiting long-term illness. The conclusion of
      the present study is that ethnicity, defined as foreign-born people, was strongly
      associated with limiting long-term illness when controlling for social, material
      and lifestyle factors.

PMID- 9015873
TI  - Contexts and patterns of men's commercial sexual partnerships in northeastern
      Thailand: implications for AIDS prevention.
AB  - Results of an exploratory research project elaborating the contexts, patterns and
      specific scenarios of the commercial sexual activity of northeastern Thai men are
      reported. Data were collected using face-to-face surveys, focus groups, key
      informant interviews and observations in 32 northeastern villages (n = 744 men),
      18 migrant labour camps housing sugarcane workers (n = 219 men), and five
      cattlemarkets in northeast Thailand. Fifty percent of married men and 43% of
      single men had visited female sex workers (FSW). Female sex worker visits
      occurred primarily prior to marriage, though 13% of married men had purchased
      sexual services within the past year. Nonmarital sexual activity was set within
      the socio-cultural frameworks of poverty, circular migration, a large commercial
      sex sector, and a belief system about men's sexuality and men's and women's
      gender roles. Sexual services were typically purchased as part of friendship
      group partying (paiy tiaow) and generally included heavy alcohol consumption. The
      most common scenario for visiting FSWs involved brothels, though cattlemarkets,
      festivals, and migrant labour situations were also scenarios for FSW contact.
      These each had unique characteristics that affected the likelihood that condoms
      would be used. The further the specifics of a scenario (as evaluated by men)
      diverged from those of brothel contact with an FSW, the less likely men were to
      identify this as having the potential for HIV transmission and the less likely
      they were to use a condom. AIDS prevention campaigns must be developed that are
      sensitive to the socio-cultural framework, contexts and specific scenarios within
      which nonmarital sexual contacts occur.

PMID- 9015874
TI  - White, red and black: colour classification and illness management in Northern
      Ghana.
AB  - Health care facilities in Northern Ghana are not only too few, ill-equipped and
      under-supplied, they are also underutilized. Health care personnel have often
      noted the irony in the fact that the sick do not make use of the health care
      facilities when they most need them. Rural peoples often wait until the illness
      has become so serious that even with emergency measures there is little hope of
      survival. The author maintains that the causes of this are not simply the lack of
      community education, the lack of warmth and friendliness on the part of poorly
      paid health workers, their perceived inefficiency, the great distances to be
      travelled and the constant shortages of medication. More constraining than all of
      these are the conflicting cultures of illness management. In a time of otherwise
      rapid social and cultural change, peoples of Northern Ghana have not often
      responded to Western medical systems in ways judged appropriate to such systems
      and have strongly resisted education or coercion to adapt to them. The author
      maintains that the classificatory systems controlling illness management among
      the Anufo of Northern Ghana and among others of that locale are colour-coded.
      This coding of "white", "red" and "black" is not simply a convenient way to
      classify types and stages of illness, or other aspects of life, but it orders and
      prescribes social roles and responsibilities vis-a-vis the sick person and the
      illness itself. In such systems, illness is thought to progress from a "white"
      stage to the "red" to the "black" or return to the "white". At the onset of the
      illness, the white stage of individual action, innovative self-help measures are
      encouraged. But once the illness becomes serious it enters the red stage and
      innovative measures cease as the more conservative, traditional machinery for
      problem-solving takes over. The whole community becomes involved. Their roles and
      functions are strictly prescribed and stringently adhered to. Deviations are
      thought to exacerbate the problem. When all of the standard social obligations
      required in this system of illness management have been fulfilled and the person
      either becomes better or moribund (i.e. the situation is reclassified to either
      "white" or "black"), once again there is room for individual experimentation, and
      other forms can be tried. In Northern Ghana traditional structures of illness
      management block Western biomedical therapy at the exact moment when innovations
      would be most effective and encourage the inappropriate use of biomedical drugs
      and therapy at other times. The author maintains that in Northern Ghana and
      possibly in other rural areas of Africa an emic understanding of the roles and
      functions that are rigidly adhered to at the emergency "red" stage can help the
      Western medical systems to be more flexible in adapting to traditional systems of
      illness management.

PMID- 9015875
TI  - The development of a training model to improve health professionals' skills, self
      efficacy and outcome expectancies when communicating with cancer patients.
AB  - Health professionals such as doctors and nurses are in a key position to help
      reduce the high prevalence of affective disorders and psychological problems
      experienced by cancer patients. This role, however, is inhibited by ineffective
      communication practices which include the use of distancing strategies and
      avoidance by the health professional. A number of contributory factors such as
      skill deficits and anxiety about negative consequences for the patient and the
      health professional have been identified in previous research and brief problem
      focused training workshops developed to address these factors with only limited
      success. Researchers in applied psychology have recommended that the development
      of training programmes and their evaluation are based upon approaches which take
      into account cognitive and affective factors as well as change in skills. The aim
      of this paper is to develop a conceptual model of communication behaviour in the
      cancer setting. The model aims to take account of the role that knowledge and
      skill deficits, self-efficacy and outcome expectancy beliefs and perceived
      support plays in the ability and willingness of health professionals to assess
      their patients' concerns. It has been applied to guide the development of a
      revised approach to brief, problem-focused workshops for health professionals. It
      also allows a systematic and multi-dimensional evaluation of training outcomes.
      Preliminary results indicate this is a promising area of communications research.

PMID- 9015876
TI  - Marital status and quality of relationships: the impact on health perception.
AB  - Using data from the National Survey of Families and Households (1987-88), this
      study investigates how a variety of family conditions (including marital status
      as well as the quality of marital and cohabiting relationships) influences global
      health perception among 12,274 American adults. Health perception tends to vary
      according to different subcategories of the unmarried status. Logistic regression
      analyses indicate that health perception depends on marital status as well as on
      the quality of marriage and cohabitation. The health impacts of marriage are also
      determined by social network support.

PMID- 9015877
TI  - Measuring the human cost of a weak economy: does unemployment lead to alcohol
      abuse?
AB  - This paper uses two-stage instrumental variables methods to examine whether
      unemployment affects alcohol use and symptoms of dependence, and if so, in which
      direction. Data were obtained from the 1988 National Health Interview Survey. The
      outcomes examined were average daily consumption during the previous two weeks
      and a summary measure of the number of symptoms related to alcohol dependence
      during the previous year. After eliminating potential bias due to reverse
      causality, evidence was found that non-employment significantly reduces both
      alcohol consumption and dependence symptoms, probably due to an income effect.
      Involuntary unemployment had a mixed effect-job loss increased the consumption of
      alcohol in the overall sample but reduced dependence symptoms among single
      respondents. Studies of the impact of alcohol use on economic outcomes should
      take potential reverse causality into account.

PMID- 9015878
TI  - Alcohol abuse and mortality: a 40-year prospective study of Norwegian conscripts.
AB  - The availability of a 40-yr prospective study of more than 40,000 Norwegian men
      born in 1932-33 constituted the point of departure for assessing excess mortality
      in alcohol abusers as well as proportions of premature deaths in men attributable
      to alcohol abuse. The conscripts were medically examined at the military
      screening, alcohol abuse was categorized for those registered as admitted to
      alcohol treatment units over a 35-yr period from 1951 to 1987, and these data
      were further linked to the national death register in 1991. A total of 4468 men
      died before the age of 60 (10.8% of the sample). Alcohol abusers were found to
      have an overall excess mortality of 3.3, increasing with age. The cumulative risk
      of death before the age of 60 yr was estimated to 0.405 for the alcohol abusers,
      and at least 6.7% of all deaths before the age of 60 could be attributed to
      alcohol abuse. Presence of chronic diseases at conscription did not confound the
      estimates of excess mortality in alcohol abusers, neither was any significant
      interaction between chronic diseases at conscription and later alcohol abuse
      found with respect to mortality. The most prevalent causes of death in the total
      sample were, in descending order, cardiovascular diseases, malignant tumors, and
      accidents. The relative risks for alcohol abusers of death from
      accidents,cardiovascular diseases, and malignant tumors were estimated as 3.2,
      2.5, and 1.8, respectively.

PMID- 9015879
TI  - Socioeconomic factors and dental caries in developing countries: a cross-national
      study.
AB  - The purpose of the present study was to analyze statistically correlations
      between socioeconomic factors and the prevalence of dental caries in developing
      countries. The DMFT index, which evaluates the incidence of dental caries, showed
      a positive correlation (P < 0.01) with several socioeconomic factors, such as
      life expectancy, adult literacy rate, school attendance rate, population employed
      in the service sector, population aged 15-64 years, and urban population.
      According to multiple regression analysis, population aged 15-64 years,
      population employed in the service sector, and urban population were the most
      influential independent socioeconomic variables, in descending order, with a
      regression coefficient of 0.635 and a coefficient of determination of 0.404 (P <
      0.001). This finding suggests that the prevalence of dental caries in developing
      countries increases with the degree of urbanization.

PMID- 9015880
TI  - The narrative of AIDS among the Tonga of Zambia.
AB  - The Tonga of Southern Zambia usually refer to a traditional disease, kahungo,
      when talking about AIDS. Such an association of AIDS with a traditional disease
      could easily be interpreted as a cultural obstacle to an understanding of AIDS
      and thus to a change of behaviour. However, a close investigation shows that this
      association is not the result of categorical thinking, but rather of narrative
      logic. What people are actually articulating when they associate AIDS with
      kahungo is a narrative about order, disorder and respect for existing rules and
      values of the society. The paper investigates how the dynamic notion of narrative
      may help us to get a better understanding of how people work towards a shared
      understanding of a new disease, and the implications this may have for AIDS
      education. It is argued that such local versions of the "story about AIDS" should
      be taken seriously and that they may contain as much "truth" as the version of
      the "North" which is usually promoted in AIDS education. AIDS education should,
      rather than being a transfer of knowledge, be an exchange of narratives and an
      attempt to "set a story in motion", that hinders the spread of AIDS.

PMID- 9015881
TI  - STDS in women attending family planning clinics: a case study in Addis Ababa.
AB  - For cultural reasons modern contraception has been slow to gain acceptance in
      Ethiopia. Knowledge about contraception and abortion is still limited in many
      family and community settings in which it is socially disapproved. By 1990 only
      4% of Ethiopian females aged 15-49 used contraception. Little is known of
      sexually transmitted disease (STD) prevalence in family planning (FP) attenders
      in Africa in general and Ethiopia in particular, even though attenders of family
      planning clinics (FPCs) are appropriate target groups for epidemiological studies
      and control programmes. A study of 2111 women of whom 542 (25.7%) attended FPCs
      in Addis Ababa showed utilisation rates to be highest in women who were: Tigre
      (33%) or Amhara (31%), aged 20-34 years (30%), age 16 or older at first
      marriage/coitus (28%:38% in those first married after 25 years); who had a
      monthly family income of 10 Ethiopian Birr (EB) or more (33%:36% for those with
      income 100-500 EB), three or more children (37%), more than five lifetime
      husbands/sexual partners (39%); or were bargirls (73%) or prostitutes (43%). The
      seroprevalence rates for all STDs, higher in FPC attenders compared with other
      women, were syphilis (TPHA) 39%, Neisseria gonorrhoeae 66%, genital chlamydia
      64%, HSV-2 41%, HBV 40% and Haemophilus ducreyi 20%. Only 4% of FPC attenders had
      no serological evidence of STD: 64% were seropositive for 3 or more different
      STD. Clinical evidence of pelvic inflammatory disease (PID) was also more common
      in the FPC attenders (54%), 37% having evidence of salpingitis. The FPC provides
      a favourable setting for screening women likely to have high seroprevalence of
      STD, who for lack of symptoms will not attend either an STD clinic nor a hospital
      for routine check up. We recommend that measures be taken to adequately screen,
      treat and educate FPC attenders, their partners, and as appropriate and when
      possible their clients, in an attempt to control STDs and ultimately HIV in the
      community. Social, economic and cultural factors in the occurrence of STDs,
      prostitution, family planning and modern contraception coverage in Ethiopia are
      identified and deficiencies of current programmes briefly discussed with the
      objective of targeting services more effectively.

PMID- 9015882
TI  - HIV prevention among Zambian adolescents: developing a value utilization/norm
      change model.
AB  - Peer-led interventions are effective in reducing risk for HIV among adolescents.
      A pre-intervention study was conducted to determine how to successfully carry out
      a possible future intervention to reduce HIV risk among adolescents in urban
      Zambia. Ethnographic and sexual data were collected on 276 males and females both
      attending and not attending secondary school during a 14-month period in 1992
      1993. Additionally, several focus groups were conducted. This paper reviews the
      cultural background of Zambian adolescents and presents an overview of the study
      results. Among the findings, it was learned that most of the male and female
      adolescents (average age of 17) are sexually active, very few routinely use
      condoms, less than half of sexually active adolescents have ever used a condom,
      AIDS is omnipresent in Zambia, the threat of HIV infection is a very real concern
      for most of the adolescents, there is a strong desire to protect themselves from
      HIV infection during sex (but condoms are often seen as ineffective and other
      forms of safer sex are not discussed), nearly all of the sexually active females
      and some of the males have received money or gifts for sex, and some of the out
      of-school females are engaging in very risky sex (e.g., unprotected anal
      intercourse, and anilingus) with adult men. The ethnographic data, including a
      brief trial risk reduction workshop, suggests that the core values and social
      norms of the adolescents may shape behavioral change. A value utilization/norm
      change (VUNC) model is developed, which is intended to provide a conceptual
      framework for understanding how to utilize selected core values of the
      adolescents to strengthen or alter norms within the social networks in order to
      elicit desired HIV risk reduction.

PMID- 9015883
TI  - HIV testing history among gay/bisexual men recruited in Barcelona: evidence of
      high levels of risk behavior among self-reported HIV + men.
AB  - As part of the first quantitative study of men who have sex with men (MSM) and
      HIV/ AIDS in Spain, anonymous, self-administered questionnaires were distributed
      via gay/lesbian organization mailings, bathhouses, and sex shops in Barcelona. We
      analyzed 547 gay/bisexual men along self-reported HIV testing history-i.e.
      untested, previously tested HIV-, and previously tested HIV +. Eleven variables
      discriminated significantly between the three groups in multivariable analysis.
      HIV- men were over-represented in the mailing subsample. While untested men
      exhibited potentially protective behaviors (e.g. least likely to have had stable
      and casual sex partners with HIV/AIDS and to practice anal intercourse), they
      were also least likely to be out with their homosexuality and most likely to
      never use condoms when they practiced anal intercourse. HIV + men were most
      likely to report insertive and receptive anal intercourse with a condom and least
      likely to practice insertive anal intercourse without a condom in the past month,
      yet they were also most likely to report the highest interpersonal barriers to
      safer sex, recent cocaine use with sex, meeting sex partners in public restrooms,
      and recent episodes of STD. A potentially volatile combination of higher sexual
      activity (e.g. more sex partners and casual sex activity) coupled with the
      presence of safer sex barriers (e.g. poor scores on indices measuring safer sex
      disposition, elevated drug use accompanying sex) was evidenced among HIV + men.
      There were no statistically significant differences between the three groups for
      anal intercourse without a condom, but with 37.5% of this collective reporting
      one such episode in the past month, all groups can be considered equally risky.
      Against the backdrop of a 20.5% self-reported HIV prevalence, there is
      considerable need for enhanced prevention efforts among gay/bisexual men in
      general and targeted strategies among HIV + men in particular.

PMID- 9015884
TI  - The (dis)embodied self in anorexia nervosa.
AB  - This paper deconstructs the debate that has been raging for over a decade between
      proponents of the feminist cultural model of eating disorders and supporters of
      the traditional medical model of illness and treatment, bringing the level of
      analysis one step deeper-to the question of the constructions of "the self"
      employed in these discourses and the implications of these constructions for the
      successful understanding and treatment of anorexia nervosa. The paper argues that
      while feminist theorizing has largely dislodged the current representations of
      anorexia nervosa from the clamps of myopic medical discourses devoid of detailed
      cultural analysis, it has in fact produced similar theoretical dichotomies and
      blind spots that preclude the successful theorizing of an embodied self and its
      particular articulation in anorexia nervosa. It is proposed here that Foucault's
      [(1986) The Care of the Self. The History of Sexuality, Vol. 3. Vintage, New
      York] notion of "technologies of the self" can provide us with a useful tool for
      bridging the split between the "inside" and "outside" produced and reified in
      both the medical model and the feminist cultural formulation of anorexia; a
      framework is suggested for the implementation of this interpretative position,
      based on a reconceptualization of the particular ritualistic behaviors associated
      in anorexia as articulating the core issues of the illness-a reconfiguration and
      repositioning of the "inside" and the "outside" as a means of tailoring the self
      along a particular line of "attitude". The essay is based on eight months of
      fieldwork counseling in an eating disorders treatment center.

PMID- 9015885
TI  - How lay is lay? Chinese students' perceptions of anorexia nervosa in Hong Kong.
AB  - Using a locally devised self-report questionnaire that encompassed both
      professional and lay explanatory models, this study explored the perceptions of
      anorexia nervosa (AN) in a large sample of 842 Chinese undergraduates who had
      little biomedical exposure to this rare condition in Hong Kong. Anorexia nervosa,
      or yan shi zheng, was conceived as a chronic psychiatric condition of severe
      weight loss (34%) that arose from mixed psychosocial etiologies. Unlike the more
      exact professional categorizations but consonant with the lexical meanings of yan
      shi and Chinese anorectic patients' illness reality, appetitive complaints,
      sadness and fat phobia were believed to be the main expressions of AN. The
      illness was seen to affect young women of affluent societies, and to call for
      help from mental health professionals as well as family members. Although it was
      not stigmatizing, it would nearly never be admired. Factor analysis revealed a
      discernible resemblance between lay and professional epistemologies, particularly
      in the configuration of anorexic symptomatology into "specific" (fat phobic) and
      "general" types. This implies that in psychiatric disease categories with an
      uncertain etiology and a substantial cultural component, lay people may package
      and construct knowledge in a fashion similar to that of professionals. The
      findings of this study question biomedicine's positivistic claim to
      psychopathology, and suggest that lay and professional ethnopsychiatric theories
      and lived anorectic experience are interdependent facets of a socially
      constructed world.

PMID- 9015886
TI  - The communication atmosphere between physician colleagues: competitive
      perfectionism or supportive dialogue? A Norwegian study.
AB  - Open and supportive communication is probably one of the most important promotors
      of learning, coping and satisfaction at the workplace. The aim of this paper is
      to describe and predict the communication atmosphere between Norwegian
      physicians. Twenty statements describing communication, as perceived by the
      physicians themselves, were presented to a random sample of the members of the
      Norwegian Medical Association of which more than 90% of the physicians in the
      country are members (N = 2628). In general, this investigation indicates that the
      communication atmosphere among Norwegian physicians is characterised by support
      and mutual respect. More than half of the respondents fully agreed that
      communication between colleagues in the workplace is marked by solidarity, and
      that experienced colleagues show respect for the less experienced in both
      personal and professional matters. Physicians working in hospitals described the
      communication atmosphere as substantially more selfish and competitive than non
      hospital physicians, whilst general practitioners considered the atmosphere
      between colleagues to be more supportive than non-specialists. In addition, high
      perceived stress was associated with the perception of a less supportive
      atmosphere. However, the strongest predictor of the communication atmosphere was
      clearly the physician's perceived autonomy. The comprehensive retrenchment
      programmes implemented in Norwegian hospitals during recent years have increased
      stress and restricted professional autonomy among both physicians and other
      occupational groups. Our findings indicate that the communication atmosphere
      necessary to secure continuity of knowledge within the medical profession may
      have been jeopardised by this process. In the long term, this may prove hazardous
      to the quality of medical care.

PMID- 9015887
TI  - Does organization matter? A multilevel analysis of the demand-control model
      applied to human services.
AB  - The demand-control model (DC model) in occupational epidemiology suggests that
      health, an individual attribute, is partly determined by work organization, via
      the interplay of demand and control, job strain. The objective of this study was
      empirical assessment of the model's tenet of an organizational determination of
      individual health. An emerging analytic method, multi-level modelling, permits
      such an assessment. The study encompasses two large Swedish human service
      organizations. It was based on a nationally representative sample of 291 local
      organizational units (level 2) with 8296 employees (level 1), a median of 18
      employees per unit. 5730 persons (69.1%) completed the questionnaire. Listwise
      deletion of missing data left a net study base of 4756 individuals in 284 units.
      Missing data were largely random. Demand and control were measured by standard
      questions and combined into a job strain index. Two such indices were calculated,
      one for quantitative demands and one for emotional demands. Individual attributes
      included age, gender, marital status, having children, social anchorage, and
      education. There were two dependent variables, self-assessed psychovegetative
      symptoms (worry, anxiousness, sadness, sleep difficulties, restlessness, and
      tension) and exhaustion (fatigue, feelings of being used up and overworked), both
      measured as summative indices. For psychovegetative health, a null model yielded
      2.2% level 2 variance, unchanging when individual attributes were included in a
      random intercepts model. Inclusion of the strain variables rendered level 2
      variance non-significant, decreasing level 1 variance by 23% and level 2 variance
      by 62%. For exhaustion, level 2 variation was 8.3% in the null model and 1.6% in
      the final model, with strain variables. The strain variables utilized in the DC
      model thus draw a substantial part of their variation from the organizational
      level. It is concluded that the claim of the DC model to rely on organizational
      factors receives support.

PMID- 9015888
TI  - Efficacy of the Tibetan treatment for arthritis.
AB  - Tibetans in the refugee communities in Northern India are exposed to both
      traditional Tibetan and Western medicine. For Tibetans suffering from arthritis
      (or trung-bo), the Tibetan treatment was compared with the Western treatment in
      an open randomized controlled trial. On a significance level of 0.0005, this
      trial demonstrated that for these Tibetans, their indigenous treatment worked
      better than the Western treatment for improved limb mobility.

PMID- 9015889
TI  - Physician vs patient initiation of psychotropic prescribing in primary care
      settings: a content analysis of audiotapes.
AB  - The primary goals of this study were to examine: (1) whether patients were
      involved actively in initiating the prescribing of psychotropic medications
      during interactions with their primary care physicians and (2) what variables
      influenced patient vs physician initiation of psychotropic prescribing. An
      analysis of 508 audiotapes of physician-patient interactions and interviews with
      each patient and physician from 11 different ambulatory care settings was
      conducted. Of 508 patients, 17% (n = 88) received prescriptions for one or more
      psychotropic medications. Forty-seven percent of repeat psychotropic
      prescriptions and 20% of new psychotropic prescriptions were initiated by
      patients. Logistic regression techniques showed that patients with higher incomes
      were more likely than their physicians to initiate psychotropic prescribing,
      whereas physicians were more likely to initiate psychotropic prescribing with
      lower income patients (P < 0.001). Patients who had more previous visits to their
      physician were as likely as their physicians to initiate psychotropic
      prescribing, whereas physicians were more likely to initiate psychotropic
      prescribing with patients who had been to see them fewer times in the past (P <
      0.05).

PMID- 9015894
TI  - Nitrato(2,3,7,8,12,13,17,18-octaethylporphyrinato)iron(III).
AB  - The crystal structure of [Fe(C36H44N4)(NO3)] has been determined in the space
      group P1. The unit cell contains two molecules. The Fe atom is displaced out of
      the porphyrin plane by 0.50 A, the average Fe-Np distance is 2.056 (1) A (where
      Np is a porphyrin N atom) and the Fe-O(NO3) bond length is 2.016 (3) A.

PMID- 9015895
TI  - gamma-Aminobutyric acid: a novel tetragonal phase.
AB  - In the tetragonal phase of gamma-aminobutyric acid, C4H9NO2, the single type of
      molecule adopts a partially folded zwitterionic form. Whereas in the previously
      characterized monoclinic phase the partially folded zwitterionic molecules
      exhibit a gauche conformation with respect to the C2-C3 bond, in this phase the
      molecules exhibit a trans conformation. The altered pattern of intramolecular
      N...O distances may be of significance with respect to the neurotransmission
      behavior of this substance. In addition to three strong hydrogen bonds involving
      the three H atoms bound to the N atom, as in the monoclinic phase, there is a
      fourth weaker one which results in a two-center bifurcated bond. There is also
      evidence suggestive of an intramolecular bridging hydrogen bond involving the N
      atom, an O atom and a methylene H atom, as previously proposed as a stabilizing
      factor for the gauche conformation observed in the monoclinic phase.

PMID- 9015896
TI  - 2-Acetylbenzoic acid: phthalide form.
AB  - In the structure of the phthalide form of 2-acetylbenzoic acid, C9H8O3, there is
      a single type of hydrogen bond. Each molecule donates one and accepts one
      hydrogen bond. The hydrogen-bonded molecules form sets of puckered ribbons
      running along the c direction which are not crosslinked to each other. The
      dihedral angle between the planes of adjacent molecules along a hydrogen-bonded
      ribbon is 77.4(1) degrees.

PMID- 9015897
TI  - Coumarin-3-carboxylic acid.
AB  - In the structure of the title compound, C10H6O4, there is a single intramolecular
      hydrogen bond. In addition, there are a number of significant intermolecular C
      H...O attractive interactions. These interactions account in part for the rather
      high density for an ordinary monocarboxylic acid, 1.522 Mg m(-3).

PMID- 9015898
TI  - 4-(2-Naphthyl)butanoic acid.
AB  - 4-(2-Naphthyl)butanoic acid, C14H14O2, crystallizes in the centrosymmetric space
      group P2(1)/a. The single type of hydrogen bond forms cyclic dimers about
      inversion centers. The carboxylic-O atoms are ordered as is the acid-H atom. The
      structure comprises double layers of aromatic rings in a herringbone array
      separated by double layers of hydrogen-bonded aliphatic strings, a pattern seen
      previously in related substances.

PMID- 9015899
TI  - sym-Hexahydropyrene.
AB  - In 1,2,3,6,7,8-hexahydropyrene, C16H16, the unsaturated rings lie essentially in
      a plane, the r.m.s. deviation of the atoms defining this plane form the best-fit
      plane being 0.006 (2) A. The saturated rings are substantially non-planar, but
      the character of the non-planarity of the saturated rings is quite different from
      that observed in octahydrochrysene. The C-C bond distances in the saturated rings
      are quite uniform, ranging from 1.505 (2) to 1.520 (2) A. No intermolecular
      distance is less than the sum of the corresponding van der Waals radii; closest
      approaches involve both C...H and H...H interactions.

PMID- 9015900
TI  - 2-Hydroxybiphenyl-3-carboxylic acid (3-phenylsalicylic acid).
AB  - In the title compound, C13H10O3, there is a single type of intermolecular
      hydrogen bond. From this is formed a cyclic dimer about a twofold axis. In
      addition, there is an intramolecular hydrogen bond which is virtually identical
      to that observed in salicylic acid.

PMID- 9015901
TI  - A cyclic side-chain-linked biphenyl ether tripeptide: H3N(+)-cyclo-[Phe(4-O)Phe
      Phe(3-O)]-OMe.Cl-.
AB  - The crystal structure of the chloride salt of H3N(+)-cyclo-(Phe(4-O)-Phe-Phe(3-O)
      OMe, cyclo-phenylalanyl-phenylalanyl-phenylalaninium chloride methyl esther,
      C28H30N3O5+.Cl(-), is described. It is oxidatively linked through a biaryl ether
      linkage formed from the hydroxyl of 4-hydroxyphenylalanine and the meta position
      of the distal phenylalanine residue. This is the first reported crystal-structure
      determination of a cyclic 17-membered biphenyl ether tripeptide, a class which
      includes the natural products K-13 and OF4949 I-IV. An unusual C-H...O hydrogen
      bond is formed between the methine H atom of the N-terminal C alpha and a
      carbonyl-O atom of a neighboring molecule [C...O = 2.995 (4) A].

PMID- 9015902
TI  - Health Affairs index 1992-1996.

PMID- 9015904
TI  - Report from the XVIIth Congress of the European Society of Cardiology,
      Birmingham, UK, 25-29 August 1996.

PMID- 9015903
TI  - Making money out of babies: rights without responsibility.

PMID- 9015905
TI  - Audit of patient acceptance of nasal surgery as a day case procedure.
AB  - A greater emphasis on day case surgery within the health service is seen as a
      method of improving efficiency and reducing expenditure. We interviewed 90
      consecutive patients undergoing nasal surgery who had been preoperatively
      assessed as being fit for day case surgery. They were randomised into three
      groups regarding the duration of postoperative nasal packing. All patients stayed
      overnight following surgery and were interviewed prior to discharge. Some 52% of
      the overall sample would be happy to have nasal surgery performed as a day case.
      If the nasal pack was removed after two hours, this figure rose to 67%. This
      difference in patient acceptance did not attain statistical significance overall,
      but there was a significant difference in those undergoing submucosal resection.
      There was no difference in the age, sex distribution or type of surgery performed
      between each group. The audit commission quotes patient satisfaction with day
      case surgery at 80%. Nasal surgery was not examined in their report, but was
      included as one of a set of procedures suitable for consideration. Although day
      case nasal surgery may be safe, further research regarding patient acceptance is
      required.

PMID- 9015906
TI  - Lansoprazole plus clarithromycin: evaluation of a new dual therapy for
      Helicobacter pylori eradication.
AB  - The aim of this pilot study was to evaluate the efficacy and safety of
      lansoprazole plus clarithromycin for eradication of Helicobacter pylori. A total
      of 26 patients with H. pylori infection were randomised to receive
      clarithromycin, 500 mg t.i.d. for 14 days, plus either lansoprazole, 30 mg o.m.,
      (group L30, n = 13) or lansoprazole, 30 mg b.i.d., (group L60, n = 13). H. pylori
      status was determined pre-treatment and four to six weeks after completion of the
      study medication by histology and 13C-urea breath test. Two patients were unable
      to complete the course of medication. Of the remaining 24 patients, 14 (58%)
      successfully eradicated H. pylori--8/12 (67%) patients in group L30 and 6/12
      (50%) in group L60. Side-effects were experienced by 17/26 (65%) of patients,
      most commonly a taste disturbance. The results from this pilot study suggest that
      dual therapy with lansoprazole plus clarithromycin is only a moderately effective
      regimen for eradicating H. pylori.

PMID- 9015908
TI  - A study to investigate the comparative efficacy and tolerability of nisoldipine
      coat-core and atenolol in the treatment of mild to moderate hypertension.
AB  - The efficacy and tolerability of nisoldipine coat-core (nisoldipine CC 10, 20, 40
      mg) and atenolol (50, 100 mg) were compared in 230 patients with mild to moderate
      essential hypertension. Treatment was titrated at two-weekly intervals as
      necessary to control blood pressure. After eight weeks of active therapy, the two
      treatments proved to be equally effective in reducing sitting diastolic blood
      pressure (13.7 +/- 8.3 mmHg and 14.2 +/- 9.1 mmHg for nisoldipine CC and
      atenolol, respectively), and provided equivalent reduction in systolic blood
      pressure and identical response rates (69%). Heart rate was reduced from baseline
      in the atenolol group but remained unchanged in the nisoldipine CC group (p <
      0.001 difference between the two groups). Both nisoldipine CC and atenolol were
      well tolerated and had no detectable metabolic effects. Adverse events were minor
      and of the type commonly associated with drugs of these classes.

PMID- 9015907
TI  - A clinical comparison of intranasal budesonide with beclomethasone dipropionate
      for perennial non-allergic rhinitis: a 12 month study.
AB  - To evaluate possible differences in efficacy and safety between budesonide and
      beclomethasone dipropionate when used intranasally in the treatment of perennial
      non-allergic rhinitis, a 12-month open study was undertaken in 24 patients
      suffering from perennial non-allergic rhinitis. Both drugs were applied
      intranasally from pressurised aerosols at a daily dosage of 400 micrograms. On
      entry and at visits after 1, 2, 4, 6, 9 and 12 months, rhinoscopy was performed
      and the severity of nasal symptoms graded according to a four-point rating scale.
      All nasal symptoms were reduced from baseline during the treatment period in both
      groups. Tachyphylaxis was not observed. No clinically significant changes in
      haematology or blood chemistry parameters were observed in either group, and
      analysis of plasma cortisol levels revealed no influence of either drug on the
      hypothalamic-pituitary-adrenal axis. Local adverse reactions were uncommon and
      mild. Budesonide and beclomethasone dipropionate used intranasally at 400
      micrograms per day were found to be safe, and budesonide was found to have a
      significantly higher (p < 0.05) efficacy than beclomethasone dipropionate in
      alleviating symptoms of perennial non-allergic rhinitis.

PMID- 9015909
TI  - Calcitonin treatment in reflex sympathetic dystrophy: a preliminary study.
AB  - Reflex sympathetic dystrophy is one of the important complications effecting the
      rehabilitation programmes of hemiplegic patients in a negative manner by causing
      pain and function loss. In this study, the aim was to investigate the effects of
      salmon calcitonin treatment in reflex sympathetic dystrophy that develops in
      hemiplegia. Forty-one patients with hemiplegia resulting from cerebrovascular
      events and stage 1-2 reflex sympathetic dystrophy were included in the study.
      Salmon calcitonin, 1 x 100 IU/day intramuscularly for 4 weeks, was administered
      to 25 of these patients (calcitonin group) to the other 16 patients physiological
      saline, 1 ml/day intramuscularly for 4 weeks, was administered (control group).
      At the end of the fourth week of treatment the pain score of the calcitonin group
      was significantly lower than that of the control group. Shoulder abduction and
      external rotation, wrist flexion and metacarpophalangeal extension of the
      calcitonin group were found to be significantly better than those of the control
      group. In the calcitonin group the significant decrease in pain and tenderness
      resulted in improvement of range of motion and motor functions.

PMID- 9015910
TI  - Modern lines of management of ectopic pregnancy.
AB  - The recent increase in the incidence of ectopic pregnancies was associated with
      rapid improvement in the diagnostic and therapeutic techniques. Quantitative
      serum B-HCG radioimmunoassay and high resolution vaginal ultrasonography have
      facilitated early diagnosis of ectopic pregnancy allowing a more conservative
      approach to patient management. Different conservative surgical and medical lines
      of management recently developed were associated with and increased chance of
      subsequent intrauterine pregnancy with no increase in the incidence of repeat
      ectopic pregnancy. Outpatient systemic medical treatment seems to be a preferred
      alternative to conservative surgery. In selected cases, it is associated with a
      lower complication rate and promising result for fertility.

PMID- 9015911
TI  - Antidepressant therapy and behavioural competence.
AB  - Major depression can impair an individual's motivation to perform routine daily
      activities and cause a deterioration in cognitive and psychomotor function. Some
      antidepressants add to pathological dysfunction through unwanted side-effects.
      Although most patients eventually recover as a simultaneous consequence of
      tolerance and therapeutic response, some may not. Where side-effects continue to
      retard normal recovery they can be called behaviourally toxic, which can be
      classified as disruptive, inhibitory or provocative. Disruptive behavioural toxic
      effects are measured using either psychometric tests or simulations of real-life
      activities (for example, a driving test). There are no widely-accepted tests for
      inhibitory or provocative behavioural toxicity, and assessments of
      antidepressants are made on the basis of case studies. This review summarises the
      results of psychometric and real-life simulation tests and compares the effects
      of antidepressants on behaviour competence. The purpose is to identify those
      drugs that seem to be the most and least likely to produce behavioural toxicity.

PMID- 9015912
TI  - Instant lithium monitoring: a clinical revolution in the making.
AB  - The recent availability of portable ion selective electrodes (ISE) for clinical
      applications has enabled lithium estimations to be performed instantly and at
      close proximity to patients. The significance of this is, not in the accuracy of
      the determination, but in the speed of the feedback provided to doctor and
      patient, and hence the promotion of compliance. The impact of this on lithium
      therapy can only be described as a clinical revolution in the making.

PMID- 9015913
TI  - A post-marketing surveillance study of Voltarol 75 mg SR in the primary care
      setting.
AB  - A total of 7438 patients suffering from a wide variety of painful conditions was
      included in the final analysis of a post-marketing surveillance (PMS) study
      monitoring the use of Voltarol 75 mg SR in a primary care setting. Follow-up data
      were collected at visits conducted one, four and 12 months after the initial
      consultation. Improvement of symptoms was the most common reason for
      discontinuation of treatment (47% of patients who discontinued). Adverse events
      led to the withdrawal of 18% of patients overall. The rate of serious
      gastrointestinal complications was low (0.4%) and deleterious hepatic or renal
      effects were not apparent. There were significantly more events experienced by
      female patients and there was a significant effect of age on severe
      gastrointestinal events. In this PMS study Voltarol 75 mg SR was used
      successfully once or twice daily without any unexpected adverse effects in a
      manner consistent with current recommendations for the use of non-steroidal anti
      inflammatory drugs.

PMID- 9015914
TI  - Pseudoephedrine toxicity in renal failure.
AB  - A case of pseudoephedrine toxicity is reported in a man with chronic renal
      failure. The effects of renal impairment on the metabolism of pseudoephedrine are
      discussed and the implications of the widespread availability of the drug in
      proprietary cold remedies are highlighted.

PMID- 9015915
TI  - Hairdryer syncope.
AB  - Six cases of hairdryer syncope are presented. This is a recurrent phenomenon,
      never previously described in medical literature, though it has been recognised
      for some time by some hairdressers. Elderly ladies sit under hood hairdryers at
      hairdressing salons for periods of up to 30 minutes. We observed that under these
      circumstances, some ladies attended the Accident and Emergency department with a
      history of 'fainting'. A brief survey of hairdressers was conducted around the
      Stockport area. Possible causes of hairdryer syncope are discussed.

PMID- 9015916
TI  - Cough mixture induced psychosis.
AB  - Cough mixture is the third most commonly abused substance in Hong Kong. Over the
      last two years, ten cases of cough mixture-induced psychosis were admitted to a
      University hospital. All of them were clinically indistinguishable from paranoid
      schizophrenia, but the psychotic symptoms often resolved promptly with the
      cessation of cough mixture use or a small dose of haloperidol. A representative
      case is described. The possible underlying aetiological mechanism and the
      treatment principle are discussed.

PMID- 9015917
TI  - An unusual cause of dysphagia.
AB  - We report a rare case of a bronchogenic cyst in an adult presenting with
      dysphagia. The benign nature of the lesion was established preoperatively by a
      series of radiological investigations. This enabled surgical planning and
      prediction of prognosis. The presentation, radiological findings and its
      differential diagnosis are discussed.

PMID- 9015918
TI  - Heparin induced thrombocytopenia causing life-threatening postoperative
      haemorrhage.
AB  - Heparin is ubiquitously employed in surgery in the prevention and treatment of
      thromboembolic disorders. A small but significant number of patients receiving
      heparin develop thrombocytopenia and are at risk of both serious thromboembolic
      disease and haemorrhage. A case is reported where a young woman developed life
      threatening postoperative haemorrhage associated with heparin induced
      thrombocytopenia (HIT).

PMID- 9015919
TI  - Autoimmune encephalopathy after treatment of thymoma-associated myasthenia
      gravis.

PMID- 9015920
TI  - Ruptured diaphragm: the latent phase.
AB  - Traumatic rupture of the diaphragm is an uncommon injury which can be missed
      unless there is a high index of suspicion. In the interval between rupture of the
      diaphragm and herniation of abdominal contents, signs and symptoms are
      nonspecific and the chest X-ray may be normal.

PMID- 9015921
TI  - Gastroenteritis causing critical limb ischaemia.
AB  - Six days after admission to hospital with Salmonella gastroenteritis, this
      patient presented with a critically ischaemic leg, having developed an iliac
      occlusion, and a subcutaneous Salmonella abscess in the anterior compartment of
      the leg. Critical limb ischaemia and abscess formation can be added to infective
      aortic aneurysm as vascular complications of Salmonella gastroenteritis.

PMID- 9015922
TI  - Serum anion gap: reevaluation of normal values.

PMID- 9015923
TI  - Cardiac tamponade in a 21-year-old body builder with anabolica abuse.

PMID- 9015924
TI  - Pernicious anaemia patients should be searched for iron deficiency during follow
      up.

PMID- 9015925
TI  - Angioedema and acute asthma attack due to the unexpected occurrence of aspirin in
      an over-the-counter cold preparation.

PMID- 9015926
TI  - Study of gastric emptying in patients with pancreatic diabetes (chronic
      pancreatitis) using acetaminophen and isotope.
AB  - The gastric emptying function tests were carried out in eight patients with
      pancreatic diabetes, who were classified into two groups according to the
      coefficient of variation in the R-R interval in ECG (C.V. R-R) on the normal
      subjects: < or = the mean - 2SD (the autonomic nerve dysfunction group: AND+
      group) and > the mean - 2SD (the autonomic nerve normal group: AND- group). Both
      the gastric emptying of liquid food by the acetaminophen method and that of solid
      food by the isotope method were significantly reduced in the AND+ group than in
      the AND- and normal groups. In addition, a significant correlation was found
      between the C.V. R-R and the serum acetaminophen concentration (a 45 min value)
      and the % gastric retention of isotope (a 120 min value). The above results
      demonstrated that even pancreatic diabetes might be complicated by gastroparesis
      diabeticorum among autonomic nerve dysfunction. There was a close relation of
      delayed gastric emptying to the C.V. R-R in ECG or an index of the vagus nerve
      function.

PMID- 9015927
TI  - Severe acute pancreatitis: pathophysiologic mechanisms underlying pancreatic
      necrosis and remote organ damage.
AB  - Despite advances in surgical and intensive care the mortality of severe acute
      pancreatitis still ranges between 10 and 20%. Fundamentally, the severity of
      acute pancreatitis, both in term of propensity and intensity of locoregional and
      remote complications, relies on the development of regional necrosis, the extent
      of the necrotizing process and the bacterial contamination of these necrotic
      areas. Intraacinar activation of pancreatic enzymes, overstimulation of
      inflammatory effector cells and vascular mechanisms are the 3 inter-related
      factors, acting sequentially to promote the severity of the inflammatory
      reaction, the ensuing necrosis and the emergence of locoregional complications.
      Numerous toxic substances, including inflammatory mediators, are released by this
      inflammatory retroperitoneal necrotizing process, gain access to the systemic
      circulation and mediate remote organ dysfunctions. Nowadays, pancreatic infection
      whose occurrence is mainly dependent upon the volume of necrosis and secondary
      bacterial translocation from the gut, accounts for 80% of the mortality in acute
      pancreatitis. The understanding of the pathophysiologic mechanisms underlying the
      inflammatory necrotizing process is critical so that the extent of necrosis can
      ultimately be limited at an early stage and these patients may be granted a
      better outcome.

PMID- 9015928
TI  - Pancreatitis and cytokines.
AB  - The pathogenesis of acute and chronic pancreatitis involves multiple mechanisms
      participating in the development of inflammation, necrosis and fibrosis.
      Cytokines able to modulate inflammatory process, tissue repair or fibrosis
      development have gained growing interest in this disease. This paper reviews the
      current knowledge about the role of cytokines in pancreatitis.

PMID- 9015929
TI  - Lithostathine: place in chronic pancreatitis, pathogenesis.

PMID- 9015930
TI  - Physiopathology of ascites in portal hypertension.
AB  - Ascites is a frequent complication of sinusoidal and postsinusoidal or
      posthepatic forms of portal hypertension. Its pathogenesis can be divided into
      factors favouring the efflux of fluid from the vascular to the peritoneal space,
      factors favouring the accumulation of fluid in the peritoneal compartment and
      factors responsible for the repletion of the intravascular volume and hence the
      continuous formation of ascites. In decompensated cirrhosis, this repletion is
      realized by renal retention of sodium and water due to activated neurohumoral
      systems. The peripheral vasodilation theory can explain most of the
      physiopathological events in cirrhosis with ascites. Some observations, however,
      oppose this theory. Hence, recently a modification of the theory was proposed in
      order to reconcile some apparently conflicting studies. The origin of the
      vasodilatory state in portal hypertension appears to be multifactorial. Most
      reports indicate that an increased vascular production of nitric oxide, a potent,
      locally acting vasodilator, plays an important role in the pathogenesis of the
      peripheral vasodilation in portal hypertension.

PMID- 9015931
TI  - Ascites: medical therapy and paracentesis.
AB  - An overview is given of diagnostic determinations to be carried out on ascites
      fluid, and on the medical therapy as based on our knowledge of the
      pathophysiology. Paracentesis has become more frequently used. It is slightly
      more effective than therapy with high doses of diuretics and carries less side
      effects. Longterm studies are needed to investigate whether albumin can be safely
      substituted by dextran-70 or haemaccel.

PMID- 9015932
TI  - TIPS for refractory ascites: neither hemlock nor panacea. The Montreal experience
      and review of the literature.
AB  - Refractory ascites worsens the end-stage course of decompensated cirrhosis.
      Transjugular intrahepatic portasystemic shunt (TIPS) has been proposed to treat
      this condition with erratic success, inducing controversial reports on the risk
      benefit ratio associated to this technique. In order to assess the usefulness of
      TIPS for this indication, this paper updates some definitions concerning the
      refractory ascites. We also analyze the main complications of TIPS and review
      some physiopathological pathways, taking peculiar interest in the Montreal
      experience.

PMID- 9015933
TI  - Intraductal papillary-mucinous tumours of the pancreas. Clinical and radiological
      aspects.
AB  - Intraductal papillary-mucinous tumours are rare epithelial tumours with all
      intermediate types occurring from papillary to mucin-hypersecreting forms. They
      affects generally old men and recurring pancreatitis is the main clinical
      feature. Endoscopic Retrograde Pancreatography is the best diagnostic method,
      showing large dilatation of the ducts and filling defects due to mucin's plugs or
      papillary tumour. IPMT are slow-growing and have low malignant potential; as to
      far, surgical resection is considered mandatory, however, better distinction
      between benign and malignant evolution will probably select cases in which
      conservative follow-up may be proposed.

PMID- 9015934
TI  - Perianal condylomata acuminata.
AB  - Anal and perianal condylomata acuminata are warts caused by infection with the
      human papillomavirus (HPV). The annual incidence of genital warts seems to have
      increased during the past few decades. Approximately 1.5 million consultations
      per year take place in the United States with this condition (1). Papillomavirus
      is a sexually transmitted disease, and is associated with several other venereal
      infections as well as with intraepithelial neoplasia and invasive squamous
      carcinoma. Only certain genotypes of HPV are carcinogenic, and can be precisely
      identified by in situ hybridisation techniques. There are many therapeutic
      alternatives, possibly reflecting the wide variability in treatment response.

PMID- 9015935
TI  - Metastatic large-cell lung carcinoma presenting as gastrointestinal hemorrhage.
AB  - A rare case of severe small bowel hemorrhage due to jejunal metastases from a
      large-cell type carcinoma of the lung is reported. A 69-yr-old Japanese woman
      presented with complaints of mild abdominal pain and liquid tarry stools 6 months
      following surgery for lung carcinoma. Gastroduodenoscopy and barium enema yielded
      unremarkable findings, although a subsequent small bowel enema revealed a large,
      15-cm ulcerated mass in the jejunum. This tumor was resected and histology
      confirmed to be consistent with a metastasis from the primary undifferentiated
      large-cell carcinoma of the lung. The patient had an uneventful postoperative
      course and survived for 9 months. There have been only two prior case reports of
      major intestinal hemorrhage secondary to pulmonary carcinoma metastases in the
      English literature. Previous reports of such metastases of the small bowel have
      bowel have documented a very poor prognosis and our patient demonstrated the
      longest survival period to date. The clinical course of this patient suggests
      that the early diagnosis and palliative surgery for this complication provide a
      more favourable outcome.

PMID- 9015937
TI  - Subtleties of antibiotic dosages--do doses and intervals make a difference in the
      critically ill?

PMID- 9015936
TI  - An unusual cause for left sided colitis: hot-water enema.

PMID- 9015938
TI  - The role of mammography in clinical practice--a review.

PMID- 9015939
TI  - Hormone replacement therapy and breast cancer risk.

PMID- 9015940
TI  - The management of internal pancreatic fistula--a collective review.

PMID- 9015941
TI  - A prospective randomised study of laparoscopic v. open cholecystectomy in aged
      patients with cholecystolithiasis.
AB  - Between August 1992 and July 1993, 27 patients aged 70 years of older with
      cholelithiasis were prospectively randomised into 2 groups. Fifteen patients
      underwent laparoscopic cholecystectomy and 12 patients underwent open
      cholecystectomy. Shorter operation time (93.3 +/- 25.3 minutes v. 176.3 +/- 26.1
      minutes, P < 0.00001), fewer postoperative analgesic requirements (0.53 +/- 0.52
      days v. 2.00 +/- 0.74 days, P < 0.00001), shorter postoperative hospital stay
      (3.93 +/- 1.71 days v. 7.92 +/- 0.79 days, P < 0.00001) and better cosmesis were
      found in the laparoscopic cholecystectomy group. The above data suggest that
      laparoscopic cholecystectomy is the treatment of choice for cholecystolithiasis
      in elderly patients.

PMID- 9015942
TI  - Modern use of neuraxial opioids in acute pain.

PMID- 9015943
TI  - The use of central venous catheters in children receiving intensive oncotherapy
      in a developing country.
AB  - Fifty-three central venous access catheters were placed in 45 consecutive cancer
      patients younger than 13 years of age. Ten of the 16 children from a very poor
      socio-economic background were discharged and received their catheter care as
      outpatients. Catheters were left in situ for a mean period of 134 days and 159
      days in the better and poor socio-economic groups respectively. In 19 cases
      catheters were removed before completion of chemotherapy. Reasons for early
      removal of catheters were technical factors in 9 patients, removal by the patient
      in 4 cases, blocked catheters or skin erosion at the exit site in 4 cases, and
      catheter sepsis in 2 patients. One febrile episode was recorded per 107 catheter
      days. Blood culture-proven sepsis occurred at a rate of 1.7 episodes per 1000
      catheter days. There was no difference in the incidence of febrile episodes
      without obvious cause in patients from a good socio-economic background (1/100
      catheter days) and in those from a socio-economically disadvantaged background
      (1/123 catheter days). The morbidity in patients from poor socio-economic
      circumstances who went home with long-term central venous access catheters in
      situ was acceptable.

PMID- 9015944
TI  - Are sutured faucial pillars really an advantage in tonsillectomy?
AB  - A prospective study was undertaken in 40 patients to determine whether suturing
      of the faucial pillars has any effect in relieving pain and discomfort associated
      with tonsillectomy. The first 20 patients (5 adults and 15 children) had
      tonsillectomy without suturing of the faucial pillars. The next 20 patients (3
      adults and 17 children) had the anterior and posterior faucial pillars
      approximated and sutured with 3.0 chromic catgut. Objective methods of evaluating
      pain and discomfort were undertaken immediately and 24 hours postoperatively. The
      pain and discomfort were the same in both groups. Adults experienced more pain
      than children, in both groups. Complications occurred in 3 patients, all
      belonging to the sutured group: 2 had palatal haematoma and 1 nasal
      regurgitation. Approximation of the faucial pillars to cover the raw tonsillar
      bed after tonsillectomy does not relieve pain. It is disadvantageous in that it
      produces complications and prolongs the anaesthetic time significantly. Therefore
      suturing of the faucial pillars is not recommended.

PMID- 9015945
TI  - Adenoid cystic carcinoma of the trachea. A report of 2 cases.
AB  - Two cases of adenoid cystic carcinomas arising from the trachea are presented.
      Epidemiology, presenting features, available therapeutic options and a review of
      the literature are discussed.

PMID- 9015946
TI  - The posterior interosseous flap for soft-tissue cover of the hand.
AB  - The management of soft-tissue defects of the hand with exposed bone and tendons
      may be difficult. The posterior interosseous flap is a fasciocutaneous island
      from the dorsal forearm, based on the posterior interosseous vessels. We have
      used this flap as a one-stage procedure to cover soft-tissue defects of the hand
      in 6 patients. It provides excellent cover without sacrificing a major blood
      vessel such as the radial artery. Although the vascular anatomy of the flap is
      normally consistent, variations exist. This prevented elevation of 1 of the flaps
      in our series.

PMID- 9015947
TI  - Dysphagia secondary to tuberculous lymphadenitis.
AB  - Oesophageal tuberculosis is a rare entity often pre-disposed to by caseating
      tuberculous mediastinal lymphadenopathy (TML). Although widely reported in
      children, TML is an under appreciated entity in adults; in this article dysphagia
      in an adult patient caused by TML is described.

PMID- 9015948
TI  - Biomechanical and perceptual determinants of drawing angles.
AB  - This study focuses on perceptual and biomechanical determinants of the kinematics
      of angular drawing movements. Two experiments are reported in which twelve
      righthanded adults were asked to draw geometrical patterns consisting of three
      segments comprising either two acute or two obtuse angles. In Experiment 1, a
      lower frequency of pauses was observed in acute patterns and their segment length
      tended to be overestimated. The former effect is attributed to the exploitation
      of elasticity (Guiard, 1993). In order to evaluate whether the latter effect was
      due to perceptual factors, a second experiment was conducted. Twelve subjects
      drew a subset of the angular patterns under normal visual conditions and under
      conditions in which they could neither see their moving limb nor the resulting
      drawing trace. Again, subjects produced more pauses at obtuse than at acute
      angles and tended to overestimate the segment length in acute patterns. It is
      concluded that pauses are likely to occur between segments of discrete movement
      sequences when potential energy needs to be dissipated. When conditions arise
      that allow subjects to exploit elasticity, however, segment length tends to
      increase. The results of Experiment 2 confirm that these phenomena are
      independent from visual perception.

PMID- 9015949
TI  - What month is it? The process of temporal orientation on a unit of the year
      scale.
AB  - The process of temporal orientation was studied in 977 subjects. They had to
      respond to one of the following questions: 'What is (was, will be) the current
      (previous, next) month?', and to explain 'how' they had come to answer as they
      did. In the majority of cases, temporal landmarks justifying the responses
      referred to the present, whatever the context of the question. The use of Future
      Landmarks increased from the beginning to the end of the month, and from the
      Previous Month question to the Next Month question. Response times varied with
      the type of temporal landmarks, and with the question context. On average, users
      of a Future Landmark responded faster. Results are discussed in relation to
      results of other studies using a 'days of the week' scale. The different use of
      past, current and future landmarks supports a hypothesis that response
      identification depends on the functional importance of the landmarks underlying a
      spreading activation process.

PMID- 9015950
TI  - Threefold effect of peripheral precues: alertness, orienting, and response
      tendencies.
AB  - Three experiments were run revealing that peripheral cues exert an alerting and
      orienting effect. Novel is the finding that peripheral cues induce a (hidden)
      tendency to respond to the cued side, which interacts with the response tendency
      elicited by the subsequent following target. Compatible S-R mappings revealed
      either a reversed or no response tendency in cue conditions as compared to uncued
      conditions. Incompatible mappings mostly showed a decrease in response tendencies
      under influence of the peripheral cue. An increase of the interval between the
      cue and the target up to 500 ms resulted in a return to the baseline condition
      (without cue). The findings for the compatible mappings may be interpreted in
      terms of an extra recoding operation that was induced by peripheral cues.
      Inconsistencies found for incompatible S-R mappings might be attributed to the
      dual presence of recoding operations on account of the cue and the target.

PMID- 9015951
TI  - A crosslinguistic study of postposing in discourse.
AB  - In this paper we examine constraints on the use of seven sentence-types
      permitting the non-canonical appearance of the logical subject in post-verbal
      position: inversion in English and in Farsi, presentational and existential there
      sentences in English, presentational ci-sentences and subject inversion in
      Italian, and es+subject postposing in Yiddish. We show that these sentence-types
      share a common discourse constraint: each requires the NP in non-canonical (i.e.
      postposed) position to represent information that is unfamiliar in some sense.
      The discourse function of postposing is contrasted with that of another sentence
      type involving post-verbal subjects: right-dislocation in English. Unlike
      postposed NPs, the marked NP of English right-dislocation represents information
      that is familiar within the discourse: concomitantly, a pronoun coreferential
      with the marked constituent appears in this constituent's canonical position. We
      argue, then, that the function of postposing is to place subjects representing
      unfamiliar information in sentence-final position. On this analysis the
      functional difference between these sentence-types and English right-dislocation
      can be straightforwardly accounted for. Given that the marked NP of right
      dislocation is coreferential with an intrasentential pronoun, we would expect
      this NP to represent a discourse-old entity, as do anaphoric pronouns in general.
      Thus, it is not accidental that right-dislocation does not serve to keep
      unfamiliar information out of subject position; the presence of the pronoun rules
      out such a function.

PMID- 9015952
TI  - Universal health coverage system.

PMID- 9015953
TI  - Interview with Mabel Dzata. Interview by Ina May Gaskin.

PMID- 9015954
TI  - Interview with: Donna Vidam, CPM. Interview by Ina May Gaskin.

PMID- 9015955
TI  - Active management of labor.

PMID- 9015956
TI  - Midwifery practice: individual freedom vs. community standards of care. Where do
      we draw the line?

PMID- 9015957
TI  - Onnie Lee Logan/Matilda Mitchell Grand midwives. Interview by Clarebeth Loprinzi
      Kassell.

PMID- 9015958
TI  - Gestational diabetes: the emperor has no clothes.

PMID- 9015959
TI  - Creating a family-centered cesarean.

PMID- 9015960
TI  - Nursing mothers are less prone to depression than those who bottlefeed.

PMID- 9015961
TI  - Childbirth Summit meetings.

PMID- 9015962
TI  - Lithuanian midwife speaks.

PMID- 9015963
TI  - Interview with Alice Sanpere, LM. Interview by Ina May Gaskin.

PMID- 9015964
TI  - Postpartum depression vs. post birth trauma.

PMID- 9015965
TI  - Intensely natural.

PMID- 9015966
TI  - Rock that baby out.

PMID- 9015967
TI  - Charting: your legal record.
AB  - Charting is an essential part of midwifery care. Charts are the backbones of our
      practice. As midwives, we talk and interact with many clients all the time. One
      way we can keep track of what we say and do with our women is by recording this
      information in the chart. The chart is considered a permanent record for the
      future; it ensures quality and continuity of care. Most importantly, it is a
      legal record.

PMID- 9015968
TI  - Two obstetricians, a baby, chicken soup and bread.

PMID- 9015970
TI  - Comparative labors: a hospital birth and a farm birth.

PMID- 9015969
TI  - Am I too "old" to be doing this again.

PMID- 9015971
TI  - A breech birth via Ma Bell.

PMID- 9015972
TI  - Report from Oslo.

PMID- 9015973
TI  - Postpartum health.

PMID- 9015975
TI  - Interview with Leon Schimmel, MD. Interview by Ina May Gaskin.

PMID- 9015974
TI  - Interview with Lynn Jordan CNM. Interview by Ina May Gaskin.

PMID- 9015976
TI  - Interview with Lynn Schimmel, NP. Interview by Ina May Gaskin.

PMID- 9015978
TI  - When the unborn give birth: special childbirth issues for adult adoptees and
      brave new babies.

PMID- 9015977
TI  - Strategies for colic.

PMID- 9015980
TI  - Sleeping beauty.

PMID- 9015979
TI  - The Mother-Friendly Childbirth Initiative. The First Consensus Initiative of the
      Coalition for Improving Maternity Services (CIMS).

PMID- 9015981
TI  - Government outlines its long-term vision for the NHS.

PMID- 9015982
TI  - Protecting nurses who work with young children.

PMID- 9015983
TI  - Ageing and quality of life. 2: Understanding successful ageing.
AB  - Older people are being maintained in their own homes for longer periods and at
      increasing levels of frailty since the widespread introduction of community care
      policies across Europe. In order to sustain a good quality of life such
      individuals are more reliant on support from both informal (family) and formal
      sources. If appropriate assistance is to be provided then there is a need for a
      better understanding of how older people maintain their self-esteem. This article
      provides additional empirical support for the processes of accommodation and
      immunization and illustrates how knowledge of these concepts is important to the
      development of improved services for older people.

PMID- 9015984
TI  - Late psychosocial effects of conditioning for BMT.
AB  - This study was designed to assess psychosocial difficulties in long-term
      survivors of bone marrow transplantation (BMT) as a possible result of the type
      of pre-BMT conditioning. Eighty-three patients replied to questionnaires
      concerning several dimensions of quality of life. These subjects were assigned to
      one of three treatment groups: subjects who had received cyclophosphamide (CY)
      and total body irradiation (TBI) (n = 43): subjects who had received the BEAM
      protocol consisting of busulphan, etoposide, cytarabine, and melphalan (n = 31);
      and subjects who had received the University College Hospital (UCH) protocol
      consisting of cyclophosphamide, doxorubicin, carmustine and thioguanine (n = 9).
      The results indicated that, although overall psychosocial adjustment seemed to be
      similar in all three groups of patients, daily activities were more impaired and
      psychological/psychosomatic symptoms were more prevalent in the combination
      chemotherapy groups. Distressing physical and psychosocial symptoms usually
      affect quality of life and the incorporation of quality of life measures in
      clinical trials of cancer treatments is of great importance.

PMID- 9015985
TI  - Alternating pressure mattresses: comfort and quality of sleep.
AB  - Comfort is particularly important for patients with terminal illness where the
      priority is to maximize quality of life. Equally important is effective pressure
      area care, as such patients are at high risk of developing pressure sores because
      of their poor general condition (Bale and Regnard, 1995). The present randomized
      controlled study set in a hospice focused on the development of methodology for
      assessing patient comfort and quality of sleep and used this to compare two
      widely used, alternating air pressure mattresses (the Nimbus II and the Pegasus
      Airwave). The Nimbus II mattress performed consistently better than the Pegasus
      Airwave in terms of patient comfort and quality of sleep. Features of the Nimbus
      II that may explain its better performance include less extreme changes in
      pressure, lower peak inflation pressures and the ability to automatically vary
      the pressure to suit the patient's position and weight.

PMID- 9015986
TI  - Aftercare under supervision: implications for CMHNs.
AB  - This article examines the implications for practice of the Mental Health
      (Patients in the Community) Act 1995, which came into force on 1 April 1996. The
      main purpose of this legislation is to introduce a system of 'aftercare under
      supervision' in the community for certain patients who have previously been
      detained under the Mental Health Act 1983, before discharge. The nominated
      'supervisor' will have responsibility for ensuring that the aftercare plan
      requirements are fulfilled. As a result of their role as community keyworkers it
      is likely that community mental health nurses will undertake this role. Careful
      consideration needs to be paid to education and training in relation to these
      responsibilities, and practitioners need to become aware of the challenges that
      such a role is likely to present.

PMID- 9015987
TI  - Administration of PRN medication by mental health nurses.
AB  - The administration of PRN medication by mental health nurses is an important, yet
      poorly explored aspect of psychiatric inpatient care. An examination of nurses'
      reasons for administering PRN medication is essential in ensuring its appropriate
      and effective use. Data were gathered from the drug charts of 44 inpatients on
      two acute psychiatric wards. Most PRN medication was given orally and the most
      frequently administered drugs were procyclidine, lorazepam, ibuprofen, diazepam
      and droperidol. The main reason for administering PRN medication was because
      patients had 'requested' it. Results were broadly consistent with previous
      research. It is recommended that nurses should give clear and specific reasons
      for administering PRN medication based on a valid assessment. Implications for
      clinical practice and further research are also discussed.

PMID- 9015988
TI  - Communication theory and the shift handover report.
AB  - The cooperation that makes human society possible is manifested most visibly
      within the organization and is almost entirely dependent upon the skill with
      which we communicate (Tortoriello et al, 1978). By understanding concepts related
      to communication theory, nurses may be better able to analyse areas of
      communication in their own practice. This article reviews the concepts of
      communication in terms of definition, function and purpose. The communication
      process model is examined and the hindrances to effective communication are
      explored. The shift handover report is analysed and related to group networking
      theory. Communication theory is then applied to the shift handover process and
      recommendations for practice are made.

PMID- 9015989
TI  - Development of day case cataract surgery: a literature review.
AB  - There is increasing demand for day case cataract surgery. This review looks at
      the varying criteria for suitable patients and compares the use of local or
      general anaesthesia for day surgery. Preassessment clinics and the possible
      limitations of patient transport are discussed. Length of stay in the day unit,
      nurse involvement and discharge procedures are examined. Postoperative visits are
      reviewed. Studies show that the clinical outcome is not affected by outpatient
      surgery and that patients report a high level of satisfaction with their day
      care. Day case cataract surgery is safe and cost-effective and increased patient
      demand will become a significant factor favouring day case surgery in the future.
      Further research into patients' attitudes to the continuity of nursing care from
      preoperative assessment, through surgery to discharge, and whether this plays a
      part in their overall satisfaction, is recommended.

PMID- 9015990
TI  - Single-case experimental designs. 1: Using idiographic research.
AB  - The single-case experimental design is an example of idiographic research which
      involves establishing causality. The reasons for using idiographic research in
      nursing are discussed and important differences between nomothetic and
      idiographic designs are highlighted in this article. Single-case experimental
      designs are recommended in situations where both true experimental and quasi
      experimental designs are difficult or impossible to use for practical or ethical
      reasons. Single-case experimental designs are ideal for nursing care situations
      because they study individual cases, making it possible to give individualized
      nursing care while simultaneously studying the outcomes of specific patients.

PMID- 9015991
TI  - Clarifying and defining nursing role developments.

PMID- 9015992
TI  - Nurse professionalization and government reform.

PMID- 9015993
TI  - The rights of the fetus against the mother.

PMID- 9015994
TI  - A practical framework for wound assessment. 2: Methods.
AB  - Accurate measurement and documentation of wound healing are essential if
      practitioners are to effectively evaluate the benefits of various treatment
      approaches. Increasingly, sophisticated wound measurement techniques are
      evolving, but many are impractical and costly. The physiology of healing and the
      relationship of each stage of this delicate process to the complex task of wound
      assessment were reviewed in part one of this article (Vol 5 (22): 1391-7) to help
      improve practitioners' clinical assessment skills. Part two will discuss ways in
      which the accuracy of simple, non-invasive measurement approaches may be improved
      so that overall alterations in wound dimension can be effectively monitored.

PMID- 9015995
TI  - Treatment of continence in people with learning disabilities: 3.
AB  - Behaviourism is a model of intervention for people with a learning disability
      which focuses on observable behaviour and methods of changing it. The
      behaviourist strategies do not typically place high value on some of the
      diagnostic labels that have been considered in the first two articles of this
      series (Vol 5(6): 364-8; Vol 5(8): 492-8). Rather, the behaviourist is concerned
      with the behaviours a particular individual shows. Behaviour modification is a
      particular methodology within psychotherapy that has many interpretations,
      ranging from a rigid orthodoxy through to an eclectic ecumenicism of theoretical
      models. The third article in this series on the management of continence in
      people with a learning disability examines the behavioural strategies that have
      been historically and are currently available to practitioners. The legacy of
      behaviour modification (1970s style) means that staff do sometimes perceive such
      strategies as treatment, whereas in fact the treatment is a combination of
      designing the environment, designing individual programmes and designing specific
      ways of developing more valuing forms of continence management.

PMID- 9015996
TI  - Faecal incontinence in adults. 2: Treatment and management.
AB  - The first article in this two-part series (Vol 5(22): 1366-74) discussed the
      prevalence, aetiology and investigation of faecal incontinence in adults. The
      second article summarizes the main treatment options available for faecal
      incontinence. Surgery is the most widely available intervention, and offers a
      reasonable chance of success for appropriately selected individuals. Drug therapy
      is currently limited to constipating agents, which can be very useful for people
      with internal anal sphincter disruption. The potential role of biofeedback is
      promising and warrants further research. Management options for people living
      with faecal incontinence are very limited and there is an urgent need to develop
      methods which enable the individual to cope with this distressing symptom.

PMID- 9015998
TI  - Parents' views of caring for children with gastrostomies.
AB  - Gastrostomy feeding devices are becoming increasingly popular. With their
      increased use in the paediatric surgical unit, it became apparent that care and
      information given to children and their families were in need of review.
      Following a literature review, a self-report questionnaire was developed to
      assess areas for change, based on parents' perceptions. The findings suggested
      that information given to all those involved in the child's care needed to be
      improved, and identified the most common problems experienced by parents when
      caring for a child with a gastrostomy. The findings had implications for future
      practice and highlighted the need for paediatric nurses to keep pace with change
      in order to ensure optimum care for children and their families.

PMID- 9015997
TI  - Minimizing hospitalization: children with newly diagnosed diabetes.
AB  - Children's recognized vulnerability to the adverse effects of hospitalization has
      resulted in the firm belief that minimization or avoidance of hospitalization is
      in children's best interests. For children with newly diagnosed diabetes, minimal
      hospitalization may be achieved through the flexibility of the paediatric
      diabetes specialist nurse role, which crosses the boundary between hospital and
      community. This study was undertaken to evaluate the effectiveness of a
      paediatric diabetes specialist nurse in reducing the length of hospitalization
      for newly diagnosed children. Using a quantitative approach, a quasi-experimental
      research design was chosen, measuring the length of hospitalization at diagnosis
      for 40 children diagnosed in the 2 years preceding, and 16 children diagnosed in
      the 9 months following, the commencement of the paediatric diabetes specialist
      nurse post. The study findings showed a significant reduction in the length of
      hospitalization, suggesting that paediatric diabetes specialist nurses, by
      minimizing or avoiding hospitalization for newly diagnosed children, can make a
      substantial contribution to their emotional wellbeing.

PMID- 9016000
TI  - Self-directed and student-centred learning in nurse education: 1.
AB  - This article, the first of two, considers the factors precipitating the
      widespread adoption of self-directed and student-centered learning in nurse
      education. It argues that these concepts have been accepted in a relatively
      uncritical fashion and that the theoretical rationale for their use has yet to be
      fully tested empirically. The results of a study of the expectations of Project
      2000 students suggest that adult learners may not necessarily want the freedom
      afforded by self-directed approaches, but may prefer a more structural and
      ordered model.

PMID- 9015999
TI  - Strategies for reducing stress and burnout in nursing.
AB  - Three models of stress-the stimulus model, the response model and the cognitive
      phenomenological-transactional (CPT) model-have been described in detail
      elsewhere (Farrington, 1995), and the notion of accepting occupational stress as
      an industrial disease has been suggested (Nursing Times, 1995). This article
      focuses on the nursing experience of stress and describes strategies for reducing
      stress and burnout on a personal and organizational level. It concludes by
      presenting a small-scale research study which examined the nature and impact of
      events perceived by postregistration nurses to cause personal psychological
      distress. The findings of the research show that certain stimuli are consistently
      perceived as being psychologically traumatizing in the daily working life of the
      student nurse. Nursing clearly remains an emotionally demanding occupation and
      more work is needed to examine the way in which events and microstressors are
      cognitively processed by nurses.

PMID- 9016001
TI  - Healthcare litigation: working towards a culture change.
AB  - This article discusses two recently published documents: the Department of
      Health's (DoH's) Executive Letter EL (96) 11 (DoH, 1996); and the Woolf Report
      (Woolf, 1996). These documents will have an important impact on healthcare
      litigation and will strongly influence the way in which clinical negligence
      claims are conducted and managed. The documents will influence clinical risk
      management strategies and the avoidance of clinical negligence.

PMID- 9016003
TI  - A new word in management.

PMID- 9016002
TI  - Political awareness in nursing in 1997.

PMID- 9016004
TI  - The impact of organizational downsizing on the job satisfaction of nurses.
AB  - Professional nurses across Canada are being affected by health reform initiatives
      designed to deinstitutionalize the health care system. This panel study examined
      the impact this restructuring has had on nurses' overall job satisfaction as well
      as their satisfaction with various aspects of their job and work environment. The
      participants consisted of 345 nurses employed in 3 community hospitals in
      southwestern Ontario. Hospital downsizing had relatively little effect on overall
      job satisfaction, satisfaction with kind of work, amount of work, and physical
      work conditions. However, compared to before the downsizing, nurses reported a
      significant deterioration in satisfaction with their career future, hospital
      identification, supervision, and co-workers following the implementation of
      restructuring initiatives. We discuss the organizational and management
      implications of these findings and suggest ways that hospital administrators can
      minimize the negative effects of downsizing on nursing professionals.

PMID- 9016005
TI  - Validity and reliability of nursing workload measurement systems: strategies for
      nursing administrators.
AB  - In Part One, an overview of the theory related to validity and reliability of
      workload measurement systems (WMSs) was reviewed. In this article, the MEDICUS
      WMS is used to provide a concrete example of the type of comprehensive validity
      and reliability programs that can be established, in an inpatient setting, on the
      basis of this theory. Practical strategies for monitoring validity and
      reliability are identified. Administrators can adapt the approaches specified to
      fit the methodology underpinning other WMSs.

PMID- 9016006
TI  - Continuous quality improvement in the care of older patients with hip fractures.
AB  - Economic restraints are forcing hospitals to develop and implement patient
      centered, cost-effective care approaches. This article describes how the quality
      of care to older patients with hip fractures was improved using Continuous
      Quality Improvement (CQI) and Managed Care processes. During a six month project,
      twenty five female patients were treated. Outcomes demonstrated that using CQI
      and Managed Care are effective in reducing mortality, complications and length of
      stay. As well, staff and patient satisfaction were very high. The structure,
      process and outcomes of this project are discussed.

PMID- 9016007
TI  - Implementing a unit based quality improvement program: one hospital's experience.
AB  - The continuous enhancement of the quality of patient care is the prime directive
      of a Nursing Quality Improvement Program. A decentralized approach, using a Unit
      Based Quality Improvement model, was used in one hospital. In this paper, the
      author examines the process from conceptualization to implementation and
      evaluation of the decentralized approach.

PMID- 9016008
TI  - Transforming our vision: emancipatory career planning for nurses.
AB  - Canadian nurses are experiencing profound and often disturbing changes in the
      health care sector. Not only have the number of jobs decreased but the nature and
      expectations of those jobs are changing dramatically. While these changes have
      raised nurses' anxiety, the changes simultaneously have presented nurses with an
      opportunity to transform their vision of nursing and their role in health care.
      This article describes a career planning pilot project for nurses which employed
      Freire's model of emancipatory learning. Based on the theoretical foundations of
      narrative psychology and critical social theory a series of four workshops were
      offered. Comments from the evaluation results indicate that the workshop was a
      transformative experience for the participants. Future implications for career
      planning for nurses are discussed.

PMID- 9016009
TI  - Organizational career development: an overview.

PMID- 9016010
TI  - Avoiding respiratory excursions: obtaining reliable pulmonary capillary wedge
      pressures.
AB  - The pulmonary capillary wedge pressure (PCWP) value provides valuable assessment
      data to guide therapeutic interventions. Proper interpretation of PCWP becomes
      complicated when respiratory excursions are imposed upon the pressure waveform.
      Critical care nurses and advanced practice nurses who understand the mechanics of
      this respiratory effect can accurately interpret the PCWP.

PMID- 9016011
TI  - Strategies to increase patient control of visiting.
AB  - Controlling patient visiting commonly evokes ambivalent feelings among critical
      care nurses. Much has been written about the needs of the family and benefits of
      social support as well as about the nurses' opinions about visitors. Nurses have
      traditionally been advocates for their patients. Critical care nurses, in
      particular, have felt a special duty to control the environment and be a
      "gatekeeper." In an effort to "protect" the patient, perhaps nurses and families
      have neglected to consult the one person who really should have the last word on
      visiting-the patient!

PMID- 9016012
TI  - Thoracoscopy: nursing implications for optimal patient outcomes.
AB  - Many patients who once were considered for open chest procedures now benefit from
      examination and treatment of pleural disease via thoracoscopy. The thoracoscopist
      enters the chest cavity through small incisions through the chest wall.
      Procedures are performed through a video assisted thoracoscope (much like a
      bronchoscope or endoscope). Wound care, maintenance of the chest drainage system,
      pain management and vigilant assessment of the cardiorespiratory system following
      the procedure are integral nursing interventions when caring for these patients.

PMID- 9016013
TI  - Pediatric pacemakers for patients with complete heart block.
AB  - Pediatric pacemaker patients have unique physiology and special care needs that
      differ from adult pacemaker patients. The critical care nurse uses information on
      the unique pathophysiology and types of pediatric pacemakers to prevent
      complications and improve outcomes for children undergoing pacemaker insertion.

PMID- 9016014
TI  - Developing an Intensive Care Continuum: incorporating rehabilitation services in
      critical care.
AB  - The Intensive Care Continuum program offers hospitals an alternative that
      effectively uses critical care beds while delivering optimum quality care to
      those patients requiring extended acute care. This program provides an intensive
      level of care while integrating rehabilitation therapies into the patient's plan
      of care. Specific strategies for developing an Intensive Care Continuum are
      offered in this article.

PMID- 9016015
TI  - Low cardiac output following cardiac surgery: critical thinking steps.
AB  - Patients often experience low cardiac output following cardiac surgery and as
      many as 90% of patients experience a decreased left ventricular ejection fraction
      (LVEF) and cardiac index (CI). Causes may vary from volume depletion to global
      myocardial dysfunction. Critical thinking skills, combined with diligent patient
      monitoring and a knowledge of cardiovascular physiology and pharmacology are
      required for prompt recognition and treatment of low cardiac output following
      cardiac surgery.

PMID- 9016016
TI  - Advance directives: do you have one?

PMID- 9016017
TI  - Reversal agents to counteract muscle relaxation: nursing considerations.
AB  - Advances in pharmacology and technology over the last decade have fostered
      expanded use of muscle relaxants in critical care units and emergency
      departments. The neuromuscular blockade facilitated by these agents may be
      reversed pharmacologically, or may be spontaneously reversed endogenously. To
      ensure appropriate patient management, the critical care nurse, clinical nurse
      specialist, and acute care nurse practitioner must have a comprehensive
      understanding of the pathophysiology of neuromuscular blockade and reversal, the
      medications involved in this process, and the critical patient assessment and
      management skills necessary to assure a positive patient outcome.

PMID- 9016018
TI  - Passy-Muir speaking valve.
AB  - The Passy Muir speaking valve is a device that facilitates communication and
      airway maintenance for patients who require artificial airways. The critical care
      nurse's role includes collaboration with speech and respiratory therapy in
      identifying, preparing, and monitoring the patient who uses the Passy Muir valve.

PMID- 9016020
TI  - To tell or not to tell.

PMID- 9016019
TI  - Retarding progression of heart failure: nursing actions.
AB  - Heart failure is a frequently encountered disorder with a guarded long-term
      prognosis. Over the past 25 years, much has been learned about the
      pathophysiology and management of heart failure. The nursing challenge
      encompasses analyzing the clinical manifestations, monitoring outcomes of drug
      therapy, and teaching the patient behaviors to retard the progression of heart
      failure.

PMID- 9016021
TI  - Improving outcomes for pediatric patients in the adult cardiac catheterization
      laboratories.
AB  - Critical care nurses are facing a new dilemma: caring for pediatric patients
      undergoing invasive cardiac procedures in the adult cardiac catheterization and
      electrophysiology laboratories. This article presents nursing standards of
      practice for the pediatric patient in these clinical settings. These standards
      promote consistency in nursing care and direct clinical practice toward achieving
      positive patient outcomes.

PMID- 9016023
TI  - [Nursing aspects of flexible bronchoscopy in premature and newborn infants].

PMID- 9016022
TI  - [Flexible bronchoscopy in newborn and premature infants].

PMID- 9016024
TI  - [Skin changes in the newborn. 4].

PMID- 9016025
TI  - [Chemotherapy: mechanism of action and management of side effects].

PMID- 9016026
TI  - [State and perspectives of nursing curricula in Germany].

PMID- 9016027
TI  - [The pediatric hospital in the year 2000--chances and risks for management and
      personnel].

PMID- 9016028
TI  - [Why do we need a new, supplemental professional qualification for specialists
      from the medical and social professions?].

PMID- 9016029
TI  - [200 years of homeopathy].

PMID- 9016031
TI  - [Breast feeding--from a sociological viewpoint. 2. Causes for the current breast
      feeding behavior].

PMID- 9016030
TI  - [The historic development of pediatric nursing--a presentation with examples].

PMID- 9016032
TI  - [Profiles in pediatric nursing--personalities and challenges].

PMID- 9016033
TI  - [Patient documentation in the light of the law].

PMID- 9016034
TI  - Safe motherhood: the long haul.

PMID- 9016035
TI  - What is your experience with birth stools? Do you recommend them? Why or why not?

PMID- 9016036
TI  - Ultrasound imaging: handle with care.

PMID- 9016037
TI  - Birth stools. In harmony with gravity.

PMID- 9016038
TI  - Twin pregnancy: exercising your options.

PMID- 9016040
TI  - Twins: a very special occurrence.

PMID- 9016039
TI  - Homebirth twins.

PMID- 9016041
TI  - A study outline on twin pregnancy, labor and delivery.

PMID- 9016042
TI  - Hide and seek twins.

PMID- 9016043
TI  - Water twins.

PMID- 9016044
TI  - The fetus frightening room.

PMID- 9016045
TI  - Postpartum streptococcal toxic shock.

PMID- 9016046
TI  - The sacroiliac joint: a major cause of backache in pregnancy.

PMID- 9016047
TI  - Molar pregnancy: a case study and review.

PMID- 9016048
TI  - Integrating water into maternity care.

PMID- 9016049
TI  - Varicella and pregnancy.

PMID- 9016050
TI  - When twins are on the way....

PMID- 9016051
TI  - Thanks, my son, for teaching me how to dance. In memory of Justin Michael
      Hendrick: April 15, 1978-May 19, 1996.

PMID- 9016052
TI  - Protocol means diplomacy.

PMID- 9016053
TI  - A rose by any other name.

PMID- 9016054
TI  - Chronic hunger and the women of the world.

PMID- 9016055
TI  - Nutritional recommendations.

PMID- 9016056
TI  - Dr. Brewer's fight to nourish pregnant women. Interview by Renee Stein and Nancy
      Wainer Cohen.

PMID- 9016057
TI  - Land food ... sea food ... brain food.

PMID- 9016059
TI  - Eating disorders and pregnancy.

PMID- 9016058
TI  - A pre-eclampsia experience.

PMID- 9016060
TI  - The arc of the pendulum.

PMID- 9016061
TI  - If she's completely satisfied, chances are she had a midwife.

PMID- 9016062
TI  - Vitamin K: is it necessary?

PMID- 9016063
TI  - Devin is born.

PMID- 9016064
TI  - Important things I've learned about birth and midwifery. International
      Confederation of Midwives.

PMID- 9016065
TI  - Why should midwives be concerned with ethics?
AB  - Is there such a thing as midwifery ethics? Yes, there is. As human beings (moral
      agents), midwives are to be ethical, moral, responsible persons and
      professionals. Midwives work in moral relationships with other persons. They
      serve by the moral standards of their profession as now embodied in written codes
      of ethics, a profession that is part of the larger health care profession. As
      part of the professional world, midwives participate in the general standard that
      to be professional is to be ethical and to be unethical is to be unprofessional.
      The professions, in turn, are part of what Eric Fromm calls "human ethics." If
      midwives are to be ethical, we suggest they need to understand ethics and to
      reason morally. Better health care for all is the result.

PMID- 9016066
TI  - The crown jewels of Nepal.

PMID- 9016067
TI  - Birth in Juarez: the point of no return.

PMID- 9016068
TI  - Heeding warnings from the canary, the whale, and the Inuit.
AB  - There is a tension between traditional and modern definitions of reproductive
      risk and normalcy. This excerpt describes that tension as it plays out among the
      Inuit of Northern Canada from the perspective of a community midwife who has
      worked with the Inuit. She presents an analytical framework which classifies and
      illuminates the types of logic that compete in most birth settings around the
      world-a framework useful for showing how some types of logic can be supervalued
      while others, such as cultural or intuitive logic, are devalued or simply
      ignored, often at great cost. The forced evacuation of all pregnant Inuit women
      from Northern Canada for the "privilege" of a hospital birth in the South
      illustrates the imbalance created when decisions purported to be based on one
      kind of logic (scientific) are in reality based on another (e.g., legal and
      clinical), or when any type of logic is given undue authority. After presenting
      the analytical framework and describing some of the history of Inuit childbirth,
      the author tells the story of one Inuit settlement's attempt to re-integrate the
      authoritative knowledge of the community by allowing Inuit midwives to choose
      their own criteria for balancing the imperatives of each kind of logic in
      decision-making for birth.

PMID- 9016069
TI  - Inuit midwives: their stories.

PMID- 9016071
TI  - Inuit birth traditions.

PMID- 9016070
TI  - 'Birth is a normal part of life'.

PMID- 9016072
TI  - Fiji: a country that loves family.

PMID- 9016073
TI  - Happy Child Foundation.

PMID- 9016074
TI  - In my opinion.

PMID- 9016075
TI  - Timing error.

PMID- 9016076
TI  - Using computers to document.

PMID- 9016077
TI  - Using E-mail and listservs.

PMID- 9016078
TI  - . . . about medication for chronic cancer pain.

PMID- 9016079
TI  - How to prevent phlebitis.

PMID- 9016080
TI  - Placing blame when a patient falls.

PMID- 9016081
TI  - Carbon monoxide poisoning.

PMID- 9016082
TI  - Peptic ulcer disease. Making a case against the prime suspect.

PMID- 9016084
TI  - Hospice nursing. A special calling.

PMID- 9016083
TI  - Isolation precautions. Clearing up the confusion.

PMID- 9016085
TI  - What you should know about cardiac stress testing. Your patient has questions-
      here's how to answer them.

PMID- 9016086
TI  - Bull's-eye! Finding the right target for i.m. Injections.

PMID- 9016087
TI  - How to deliver tragic news with compassion.

PMID- 9016088
TI  - Bringing rich resources to nursing.

PMID- 9016089
TI  - Reassuring Rita.

PMID- 9016090
TI  - Anticholinergics and cavities.

PMID- 9016091
TI  - Inserting a nasogastric tube.

PMID- 9016092
TI  - Still waiting for a bed.

PMID- 9016093
TI  - Former colleagues defend Saudi murder suspects.

PMID- 9016094
TI  - Pain management in advanced cancer.
AB  - This article explores the nurse's role in the management of pain for patients
      with advanced cancer. It relates to UKCC Professional Development categories:
      Care enhancement and Practice development.

PMID- 9016095
TI  - Back to school.

PMID- 9016096
TI  - Don't scapegoat temporary nurses.

PMID- 9016098
TI  - A stitch in time.

PMID- 9016097
TI  - Racism is real.

PMID- 9016099
TI  - Miscarriage of justice?

PMID- 9016100
TI  - Nursing with a passion. Interview by Daniel Allen.

PMID- 9016101
TI  - Mental health network: research into dementia.

PMID- 9016102
TI  - Nurse practitioners: the role in A&E and primary care.
AB  - This article describes a recent evaluation of the work of nurse practitioners
      across a range of A&E departments and minor treatment centres in west London.
      Questionnaires, face-to-face interviews and focus groups were used to collect the
      data. The authors found that across the sites in the study, the provision of
      nurse practitioner services varied in scope but were well received by staff and
      patients. Issues surrounding training remained unresolved, but the role appeared
      to be developing in response to the reduction in junior doctors' hours and
      improved and extended opportunities in pre- and post-registration nurse
      education. The authors recommend that the cost effectiveness of nurse
      practitioners should be evaluated. The accompanying commentary suggests the nurse
      practitioner role should be explicitly defined.

PMID- 9016103
TI  - Mental health nursing: making it a primary concern.
AB  - This article suggests that the focus of mental health nursing is narrowing at a
      time when nurses in other areas are widening their roles and responsibilities.
      The author calls for more co-operation between mental health nurses and their
      colleagues in primary health care.

PMID- 9016104
TI  - Obstructive sleep apnoea: diagnosis and management.
AB  - Snoring and the associated syndrome of sleep apnoea can have severe effects on
      the lives of sufferers and their families. This article discusses why obstructive
      sleep apnoea is potentially fatal, and how it may be identified and managed.

PMID- 9016105
TI  - No place for macho bosses.

PMID- 9016106
TI  - Breach of trust.

PMID- 9016107
TI  - Good on paper.

PMID- 9016108
TI  - Roll on the resolution.

PMID- 9016109
TI  - Long-term health care and the ethics of the marketplace.
AB  - This article reflects on the ageist attitudes that hold sway in he intellectual
      debate over long-term nursing care. The once proud claim of cradle to grave
      health care is being undermined with older people seen as economic dependents,
      savings being means tested and continuing care places being cut. For society to
      be seen as fair, the principle that no one should be disadvantaged because of
      circumstances over which they have little control-of which age is surely one-must
      be reinstated at the heart of the NHS.

PMID- 9016110
TI  - Make the right noises caring for hearing-impaired patients.
AB  - This paper describes a survey carried out in South Wales to elicit the views of
      patients with hearing losses after treatment by nurses and doctors. Difficulties
      with communication are shown and ways forward are highlighted. Guidelines for
      helping patients with hearing impairment are also illustrated.

PMID- 9016111
TI  - Assessment of the risks posed by people with mental illness.
AB  - This article examines the prediction of risk and dangerousness and identifies
      aspects relevant to a risk assessment by mental health professionals, in
      particular nurses.

PMID- 9016112
TI  - Ringside view from A&E.

PMID- 9016113
TI  - Diabetes. Childhood incidence.

PMID- 9016114
TI  - Yes, prime minister.

PMID- 9016115
TI  - No offence intended.

PMID- 9016116
TI  - PREP and profiles. Knowledge for practice.

PMID- 9016117
TI  - No savings from the bank.

PMID- 9016118
TI  - A special legacy of neglect.

PMID- 9016119
TI  - Broadmoor is first among equals.

PMID- 9016120
TI  - Temp staff, permanent risk. Interview by Janet Snell.

PMID- 9016121
TI  - Cognitive behavioural nursing therapy in paranoid psychosis.
AB  - This paper provides an account of cognitive behavioural interventions applied by
      nurses to a patient experiencing paranoia. The paper provides a brief review of
      the process of such interventions and incorporates a case study.

PMID- 9016122
TI  - Persecution complex: the enigma of paranoid disorders.
AB  - Understanding the clinical meaning of paranoid and defining the role of the nurse
      in stages of treatment.

PMID- 9016123
TI  - An audit of pain management in acute sickle cell crisis.
AB  - People undergoing sickle cell crisis can experience extreme pain that is not
      always managed effectively. This article describes an audit of pain management in
      sickle cell disease that was used to generate practice guidelines. A subsequent
      audit of pain management for this client group demonstrated improvements in the
      quality of care delivered.

PMID- 9016124
TI  - Making sense of ... parenteral nutrition in adult patients.
AB  - Parenteral nutrition is used to support people who have problems eating and
      drinking or who cannot absorb nutrients through their gut. This paper outlines
      the rationale for employing parenteral nutrition, the constituents of the
      solutions used and issues arising from the administration of the therapy.

PMID- 9016125
TI  - Breaking down the barriers to effective communication.
AB  - Effective communication is central to working and helping clients in a health
      care setting. However, environmental factors can inhibit good communication. This
      paper encourages retention on factors that affect communication and how they
      might be overcome.

PMID- 9016126
TI  - Loss adjusters.

PMID- 9016127
TI  - Island in the sun.

PMID- 9016128
TI  - Wound cleansing. Guidelines for A&E staff.

PMID- 9016129
TI  - It's all academic.

PMID- 9016130
TI  - PREP and profiles.

PMID- 9016131
TI  - On duty. Interview by Esther Leach.

PMID- 9016132
TI  - Pediatric nutrition support: then and now.

PMID- 9016133
TI  - Nutrition support of pediatric patients.
AB  - Nutritional management in pediatric patients is often considered to be complex
      and difficult. We review the basic rationale and principles of IV nutrition
      support in pediatric patients. The unique differences between children and adults
      are outlined. The nutritional support solution is then divided into the distinct
      sections of energy, protein, volume, electrolytes minerals and vitamins. Each of
      these parts is considered separately to allow understanding in a sequential
      fashion. Different routes of intravenous access are also discussed to include
      placement, maintenance, treatment of infections and management of catheter
      thrombosis.

PMID- 9016134
TI  - Pediatric enteral access center: a multidisciplinary approach.
AB  - The need for enteral access and gastrostomy placement in children has increased
      dramatically over the past several years. In the following article, we present a
      case report of a typical patient undergoing evaluation for enteral nutrition and
      enteral access. Following the case report, we describe our newly formed Pediatric
      Enteral Access Program including patient selection, the method of gastrostomy
      placement, risks and benefits, cost analysis, and follow-up of this ever
      increasing population of children.

PMID- 9016135
TI  - Safety and efficacy of total parenteral nutrition delivered via a peripherally
      inserted central venous catheter.
AB  - Central venous catheters for total parenteral nutrition (TPN) have traditionally
      been inserted via direct cannulation of the subclavian vein, but this technique
      requires physician participation and is associated with well-described
      complications. We report the single largest institutional experience with
      peripherally inserted central venous catheters (PICC lines) used exclusively for
      TPN in non-intensive care unit patients. From July 1991 to March 1994, 135 PICC
      lines were placed in 126 patients via the antecubital vein, advanced into the
      central venous system, and used only for TPN. Complication rates were determined
      and compared with those for TPN administered through a subclavian vein-inserted
      central catheter. Patient demographics were similar in each group with respect to
      age, type of disease process, acuity of illness, and indications for nutrition
      support. A cumulative number of 1381 TPN days (mean = 11 days per patient)
      comprised the PICC line experience. Comparison was made with 135 successive
      standard (subclavian) central lines inserted in 105 patients for TPN
      administration (1056 TPN days, mean = 10 days per patient). There was no
      difference in the overall rate of complications between the two groups. There
      were no major complications that prolonged hospitalization (eg, catheter-related
      sepsis or pneumothorax) in the PICC group compared with three such complications
      in the standard group. PICC lines can be used safely and effectively for TPN and
      are associated with an acceptable rate of complications.

PMID- 9016136
TI  - Should protein be included in calorie calculations for a TPN prescription? Point-
      counterpoint.

PMID- 9016137
TI  - Nonprotein vs total calories--what are most clinicians using?

PMID- 9016138
TI  - (Not your average) clinical rounds with a nutrition support team: a hair-raising
      case.

PMID- 9016139
TI  - Standards for hospitalized pediatric patients. A.S.P.E.N. Board of Directors.
      American Society for Parenteral and Enteral Nutrition.

PMID- 9016140
TI  - Standards for nutrition support physicians. A.S.P.E.N. Board of Directives.
      American Society Parenteral and Enteral Nutrition.

PMID- 9016141
TI  - Ethics and nutrition support.

PMID- 9016142
TI  - Feeding, withdrawing, and withholding: ethical perspectives.
AB  - Ethics questions continue to loom large in the heath care arena, as the paradigm
      of physician-driven health care shifts to health care team- and patient-driven
      care. This review describes the types of information and the process clinicians
      and patients can use to evaluate end-of-life decisions related to the
      administration of medical nutrition and hydration. The author also touches on the
      emotions that the clinicians themselves inevitably bring to the decision-making
      process.

PMID- 9016143
TI  - Forgoing artificial nutrition and hydration: legal and ethical considerations.
AB  - Decisions to withhold or withdraw life-sustaining care are daily events in most
      hospitals and long-term care facilities. When the life-sustaining care includes
      artificial nutrition and hydration, however, families and other surrogate
      decision makers sometimes reach a different conclusion than when the care
      consists of ventilation or other life support. This tendency to view artificial
      nutrition and hydration as "different" is one that is sometimes shared by
      professional ethicists and courts. Over time there has emerged, however, a clear
      consensus concerning decisions to forgo nutrition and hydration, and there is
      near-unanimity in the court decisions on this subject. The author reviews the
      arguments that have been made for and against treating nutrition and hydration as
      a special case, court decisions in which patients or their surrogates have asked
      for the termination of nutritional support, and state and federal statutes that
      have addressed nutrition and hydration in the context of living wills and the
      care of imperiled newborns.

PMID- 9016144
TI  - An oncology patient's choice to forgo nonvolitional nutrition support: ethical
      considerations.
AB  - A 76-year-old patient with metastatic carcinoid tumor who had difficulty
      tolerating an oral diet and jejunostomy feedings became dehydrated and failed to
      thrive. His jejunostomy feeding regimen was manipulated to improve tolerance
      without success. Although his medical condition was untreatable, he was not
      considered terminally ill, and he was determined to be a reasonable candidate for
      home total parenteral nutrition (HTPN). However, he thought HTPN was an
      "excessive measure," and despite lengthy discussions with him by members of both
      the Hematology/Oncology and Nutrition Support services about the potential
      benefits of HTPN, he refused any further interventions involving nonvolitional
      nutrition support (jejunostomy feedings and HTPN). He was discharged to home
      receiving an oral diet as tolerated in the care of his family and hospice. This
      case illustrates the ethical considerations surrounding a patient's decision to
      forgo medical care that might prolong life.

PMID- 9016145
TI  - The effects of rinsing enteral delivery sets on formula contamination.
AB  - This study investigated whether rinsing enteral delivery sets before formula
      addition affects formula contamination. Both a simulated and a clinical phase
      were conducted. In the simulated phase, Osmolite (Ross Laboratories, Columbus,
      OH) was infused continuously through 52 delivery sets into a flask via enteral
      infusion pumps for 24 hours. The delivery sets were randomly assigned to two
      groups of equal size. One group was rinsed with tap water before new formula was
      added at 8 and 16 hours, and the other group was not rinsed. At 8, 16, and 24
      hours, samples of formula were collected from the delivery sets, and bacteria
      counts were obtained. In the clinical phase, 23 critically ill patients receiving
      Osmolite continuously were randomly assigned to a rinse or no-rinse group. The
      same formula addition and rinse protocol from phase I was used. Formula samples
      were obtained at 24 hours. In both phases, there were no significant differences
      between the rinse and no-rinse groups with respect to bacteria counts at any time
      period. The findings suggest that rinsing may be unnecessary if delivery sets are
      used continuously for 24 hours or less; however, the possibility of a type II
      error because of the small sample size of this study must be recognized.

PMID- 9016146
TI  - Telemedicine: caring for patients across boundaries.
AB  - Telemedicine combines computer, video and telecommunications to provide
      healthcare to patients at distant sites. With the improved camera and
      transmission technologies of the 1990s, telemedicine can be used in a variety of
      situations. There are two basic technological systems: live interactive video and
      still image ("store and forward"). Potential users include patients who live in
      rural or difficult to reach geographic areas, who are confined (i.e. prison
      inmates), Telemedicine can allow ambulatory patients to continue living at home
      rather than moving into costly nursing facilities. Home telemedicine also allows
      greater responsiveness and higher frequency of visits by home care nurses,
      potentially reducing future hospital visits and costs. Two home telemedicine
      models are the personal telemedicine unit and the enhanced personal telemedicine
      module with pc-based video. Telemedicine technologies developed by the military
      for use on the battlefield that could be adapted for civilian use include medical
      simulations, individual monitoring devices and biosensors, portable retinal
      display monitors, life support for trauma/transport, and diagnostic ultrasound
      imagery. Ultimately, the benefits of telemedicine will be consistency of care,
      easy access to specialized consultants, higher responsiveness to patient needs,
      and lower overall healthcare costs.

PMID- 9016147
TI  - Wound management by constant tension approximation.
AB  - An ideal result in wound healing is expedited closure with full-thickness skin,
      as opposed to thin, fragile epithelium prone to future breakdown. To help achieve
      accelerated healing by full thickness skin, a device has been designed that
      applies constant tension traction to the wound margins. The device acts by both
      approximating the wound and by encouraging tissue and skin generation through
      stimulating angiogenesis and epithelial proliferation. This study includes 31
      patients with 36 wounds of varying etiologies treated over 28 days. The wounds
      were inspected every 3 to 5 days at which time the dressings were changed and new
      devices applied, as needed. All but five of the wounds healed completely with
      full thickness skin within the study period (average: 15 days; range: 7-28 days).
      The longest healing times occurred in the patients with pressure ulcers. Using a
      formula for determining healing time based on excisional wound dimension, the
      expected healing time of a 3cm wide foot ulcer with uninterrupted progress is 41
      days. The time for such a wound to heal in this study was 21 days. The
      approximating device accelerated wound healing by full thickness skin for the
      wounds included in this study. Other considerations when using this method
      include cost, patient compliance and indications/contraindications.

PMID- 9016148
TI  - Reimbursement challenges and how to meet them.
AB  - How we deliver healthcare in the U.S., and how that care is paid for, is
      evolving. Reimbursement and payment issues now directly impact patient care and
      clinical decisions. Comprehensive documentation is essential to receiving
      reimbursement. Therapeutic positioning used by therapists is considered a skilled
      service. The key to Medicare reimbursement for therapeutic positioning and other
      services is documentation which clearly outlines the required skills of the
      professional, the medical necessity and reasonableness of the service, and the
      significant functional and safety goals that have been met, along with the
      progress over time. Medicare coverage and payment policies for surgical dressings
      and support surfaces have been revised in the last few years. The current
      surgical dressings policy has a number of points that must be understood: X1
      modifiers, border versus non-border dressings, wound fillers and covers,
      solutions (saline), wound fillers (amorphous), dressing kits, staging, sterile
      versus non-sterile gauze, and normal utilization parameters. Many restrictions in
      both surgical dressings and support surfaces policies are efforts to curb fraud
      and abuse. The future of reimbursement depends of the involvement of healthcare
      professionals by developing research-based protocols, comprehensive
      documentation, education of both peers and patients, and political empowerment.

PMID- 9016149
TI  - Promoting healthy bladder habits for seniors.
AB  - Urinary incontinence (UI) effects people of all ages, but is especially prevalent
      in the elderly population. Also significant is a lack of knowledge about UI. A
      health promotion project was developed and implemented in six ethnically diverse,
      predominantly minority, inner city senior centers, a program designed to address
      an elder population, as they are very likely to be experiencing UI and lacking
      knowledge concerning healthy bladder habits. The project consisted of three
      phases: orientation/training of key staff members/peer educators at the six
      senior centers; educating elder consumers through four one-hour weekly sessions
      involving visual aids and completion of bladder records and quizzes, and follow
      up sessions with senior staff/peer educators to reinforce previous training. One
      result was that training of peer educators needed further refinement to allow for
      a more significant role throughout the program. The program was very well
      received by the participants and roughly 80 percent felt they had more control
      over their bladder by the end of the last session. This project will continue
      into 1997 and in addition to information on UI, the project will include prostate
      health for men and gynecological health for women, as this need became evident
      throughout the program.

PMID- 9016150
TI  - Exploring the process of a skin care team.
AB  - In early 1994, the nursing department in a 153 bed acute care facility with a
      twenty bed short-term physical rehabilitation unit noticed that patients were
      developing nosocomial skin care problems at their facility. It was found that
      patients who returned to the facility within 31 days were at risk. A one-day,
      prevalence survey was conducted which revealed the presence of a high percentage
      of pressure ulcers among the patients surveyed. A group of nurses decided to
      institute a multidisciplinary team in an attempt to solve the skin care problems,
      which resulted in the formation of a Skin Care Team. The Skin Care Team sought to
      improve the appropriateness, effectiveness, and efficiency of delivering skin
      care to patients, as well as to improve the continuity of care among healthcare
      providers in the provision of skin care services. The following article was
      written by a member of the Skin Care Team. The concept of teamwork is defined and
      explored, and a description of the developmental process of a team, specifically
      a skin care team, is also provided.

PMID- 9016151
TI  - What's new: the AHCPR guideline update on urinary incontinence.
AB  - The Agency for Health Care Policy and Research (AHCPR) released their first
      updated guideline in March, 1996. Three documents were released: the Clinical
      Practice Guideline, Urinary Incontinence in Adults: Acute and Chronic Management;
      the Quick Reference Guide, Managing Acute and Chronic Urinary Incontinence; and
      the Patient Guide, Understanding Incontinence. The new areas are outlined and
      addressed. Unlike the 1992 version, the update emphasizes the problem of urinary
      incontinence (UI) in a specific population, those with chronic "intractable"
      incontinence. It provides an algorithm in the Quick Reference Guide for selecting
      appropriate behavioral, pharmacologic, and surgical treatments and supportive
      devices for use in managing UI. The concept of "prevention" of UI and the
      promotion of healthy bladder habits is introduced. The updated guideline
      developed recommendations for each assessment and treatment method. Specific
      interventions that can impact individuals with chronic "intractable" incontinence
      are discussed including toileting assistance programs, physical and environmental
      alterations, fluid and dietary management, management of nighttime voiding, and
      other measures and supportive care. Skin care and social and organizational
      environmental factors are also discussed. In August, 1996 the AHCPR released two
      additional, original documents, the Caregiver Guide, Helping People with
      Incontinence, and Alert for Directors of Nursing, which are briefly discussed.

PMID- 9016152
TI  - Product categories and definitions for incontinence/perineal care.

PMID- 9016153
TI  - [Changes in a pediatric unit: report of an experience in the integration of
      teaching and practice of nursing].

PMID- 9016154
TI  - [Nursing education: an identity course].

PMID- 9016155
TI  - [Health politics in Brazil: historical reconstruction and current perspectives].
AB  - Authors presents an evolution of the public health's politics in Brasil through a
      critical review of the historical process. Besides this they call to the
      importance of this issue in the undergraduate curricular in nursing.

PMID- 9016156
TI  - [Between the fear of HIV contamination and the symbolic representations of AIDS:
      the specter of contemporary despair].
AB  - Lack of knowledge and misinformations on HIV/AIDS are predictors of emotional
      responses as fear of contagion, homophobia, avoidance and excessive precautions.
      Fear of contagion is an affective stress response to the neurocognitive activity
      that leads to a perceived threat of AIDS in connection with the symbolic meanings
      os illness. Focused interviews were conducted with an opportunistic sample of 31
      young people to know the affective responses and behaviors after blood screening
      for HIV antibody testing. The findings confirm the relationship of symbolic
      representation of illness as mystery, death, punishment and sexuality to fear of
      contagion and mitic conception of AIDS.

PMID- 9016157
TI  - [Leadership in the administration of nursing personnel according to the
      perceptions of nurses and nurses' aides].

PMID- 9016158
TI  - [Trying to save themselves: nurses' choices in difficult situations].
AB  - This study was originated in the interest to understand the nurse's autonomy. We
      accomplished individual interview with 8 nurses, which works in a hospital unit,
      and the focus of the interviews was their experiences in making choices in her
      settings. The analysis of the data, through fenomenologic analysis, results in
      the identification of 4 themes which explain the meanings that guidance the
      nurse's actions in work's situations, when she makes a choice. They are:
      "OBLIGATIONS AND RESTRICTIONS DEFINE THE INSTITUTIONAL ROLE OF THE NURSE",
      "IDENTIFY RESOURCES THAT SUPPORT HER ACTS", "TO FEEL WEAK FOR MAKE CHOICES", "TO
      TRY PRESERVE HERSELF". The internal autonomy was identified as a condition to the
      nurse's professional autonomy.

PMID- 9016159
TI  - [The teaching/learning process in uterine palpation and measurement: the effect
      of practice].
AB  - The present study related to the teaching-learning process concerning the uterine
      measurement and palpation technique, it was intended to analyze the influence
      practice had on the Undergraduation Nursing students' skills acquired knowledge
      by the use of that technique. Applying a standard instrument previously developed
      for this study, the students' evaluation was carried out in two phases. The
      results showed a significant improvement in the students' performance skills and
      descriptive knowledge. Thus, this study was able to stress the importance of
      practice for the motor-perceptive skills in the teaching-learning process.

PMID- 9016160
TI  - [Proposal to adapt the McGill Pain Questionnaire into Portuguese].
AB  - Pain is a multidimensional and subjective experience. The developing instruments
      for the assessment of the multiple components of pain is necessary for the
      comprehension of the suffering, to delineate therapeutic programs and to evaluate
      their efficacy. The McGill pain questionnaire has been considered the best
      instrument to assessment the sensitive-discriminative, affective-motivational and
      cognitive-avaliative dimensions of pain. The aim of this study is to present the
      adaptation of McGill to portuguese language.

PMID- 9016161
TI  - [Recovery of patients with traumatic brain injuries one year after the trauma].
AB  - A prospective longitudinal study of traumatic brain injury (TBI) patients was
      conducted to identify the recovery pattern 1 year after trauma. Patients with all
      levels of injury and age between 12 and 60 years were observed. They were
      analyzed using the eight-point Glasgow Outcome Scale (GOS) as well as their
      return to productivity in that period. The majority of victims (77.2%) made good
      recovery, that is (GOS = 0 or 1) and complete recovery or GOS 0 was achieved in
      38.6% of then. However at the 1 year mark, 22.8% of the victims showed
      disabilities. Overall, victims had returned to productivity in that period
      (83.3%) but 19.4% of them have had changes in their productivity and 16.7% didn't
      return to your job.).

PMID- 9016162
TI  - [Nursing diagnosis in patients in intensive care units].
AB  - The aim of this study was to identify the nursing care needs of patients of
      critical care unit. The nursing diagnoses of 32 patients was formulated. The data
      was collected by interview and physical examination and the Functional Health
      Patterns was the framework to collect the data and to identify the predominant
      dysfunctional health areas.

PMID- 9016164
TI  - New acute MI guidelines.

PMID- 9016163
TI  - Ethics in action. What would you do?

PMID- 9016165
TI  - Endometriosis: what you need to know.

PMID- 9016166
TI  - The human side of "mad cow" disease.

PMID- 9016167
TI  - Getting to the heart of IABP therapy.

PMID- 9016168
TI  - A nurse's guide to the Internet.

PMID- 9016169
TI  - Safeguard your license: the disciplinary process.

PMID- 9016170
TI  - A mysterious case of loose stools and GI cramps.

PMID- 9016171
TI  - Knowing all the side effects.

PMID- 9016172
TI  - [Household help. Just that or professional work].

PMID- 9016173
TI  - [The quality of domestic help].

PMID- 9016174
TI  - [Domestic child care].

PMID- 9016175
TI  - [Home health aide professions. Household worker and household aide].

PMID- 9016176
TI  - [Home help. The health project of the Rural Home Help. A global approach to
      health].

PMID- 9016177
TI  - [Home help. A disease, several responses. Home health services].

PMID- 9016178
TI  - [Colo-rectal cancer in 1996].

PMID- 9016179
TI  - [Caring for patients treated with Campto (CPT-11)].

PMID- 9016180
TI  - [Developing and promoting nursing research. Recommendation by the European
      Economic Community].

PMID- 9016181
TI  - [Chronic wound and hydrocolloid gel].

PMID- 9016182
TI  - [Nurses and drugs].

PMID- 9016184
TI  - [The end of a model].

PMID- 9016183
TI  - [Computers: a cultural revolution].

PMID- 9016185
TI  - [Nicorandil, a potassium channel agonist].

PMID- 9016186
TI  - [Once upon a time.... Institutionalized psychotherapy and the big bad fool].

PMID- 9016187
TI  - [Institutional psychotherapy. A process].

PMID- 9016188
TI  - [Institutional psychotherapy. The administration, the rats, the chicken yard].

PMID- 9016189
TI  - [Travel ... travel. I have lost my name].

PMID- 9016190
TI  - [The bad Jojo. When the saliva takes the place for words].

PMID- 9016191
TI  - [The school at the hospital or the hospital at the school. Story in one act-
      medical, love story or pedagogical?].

PMID- 9016192
TI  - [Welcome, thought, pitfall and grief].

PMID- 9016194
TI  - [A horse, why?].

PMID- 9016193
TI  - [Transfer, contact, separation].

PMID- 9016195
TI  - [Innovation and psychiatry. Phantasy or reality?].

PMID- 9016196
TI  - [My nights are nightmares].

PMID- 9016198
TI  - Does 2-year stability imply that pulmonary nodules are benign?

PMID- 9016199
TI  - Communication of the significant but not urgent finding.

PMID- 9016200
TI  - Washington in his last illness attended by Drs. Craik and Brown.

PMID- 9016201
TI  - Acute interstitial pneumonia: high-resolution CT findings correlated with
      pathology.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relation between
      pathologic phases and high-resolution CT (HRCT) findings in patients with acute
      interstitial pneumonia (AIP). MATERIALS AND METHODS: Our retrospective review
      found 14 patients with AIP who were included in this study. Three patients were
      pathologically diagnosed as having AIP by open lung biopsy, and the other 11
      patients were confirmed at autopsy. In eight of the 11 autopsy patients, the
      postmortem lungs were inflated and fixed by Heitzman's method, and a postmortem
      HRCT scan was obtained on all 11 autopsy patients. Paying special attention to
      the disease stage, we selected 27 areas of the lung from antemortem or postmortem
      HRCT and correlated them with pathologic findings. RESULTS: Nine areas of the
      lung that showed increased attenuation without traction bronchiectasis were
      associated with either the exudative (n = 5) or early proliferative (n = 4) phase
      of AIP. Eleven areas of increased attenuation with traction bronchiectasis were
      associated with either the proliferative (n = 4) or fibrotic (n = 7) phase of
      AIP. Honey-combing, observed in one area of the lung, corresponded to
      restructuring of distal airspaces and dense interstitial fibrosis. Six spared
      areas, within or adjacent to areas of increased attenuation, showed pathologic
      findings of the exudative phase. CONCLUSION: HRCT findings were not specific for
      the pathologic findings in our patients with AIP. Nevertheless, the findings of
      traction bronchiectasis in areas of increased attenuation suggested the
      proliferative or fibrotic phase.

PMID- 9016202
TI  - Imaging of pulmonary lymphomas.

PMID- 9016203
TI  - Thoracic involvement from osteosarcoma: typical and atypical CT manifestations.

PMID- 9016204
TI  - Thoracic cross-sectional imaging of amyloidosis.
AB  - OBJECTIVE: Our objective was to determine the thoracic manifestations on cross
      sectional imaging of patients with tissue-proven amyloidosis. MATERIALS AND
      METHODS: We reviewed the records of 300 patients with the diagnosis of
      amyloidosis on whom cross-sectional imaging was done at our institution between
      1985 and 1995. After exclusions, 19 patients with tissue-proven amyloidosis and
      cervicothoracic cross-sectional imaging were included. Seven patients had
      localized amyloidosis and 12 patients had systemic amyloidosis. Eighteen patients
      underwent CT scans and the remaining patient, MR imaging. RESULTS: Two patients
      with systemic amyloidosis had widespread noncalcified adenopathy. A third patient
      had an infiltrative soft-tissue process in the mediastinum and axillae containing
      thick linear and focal calcifications. Five patients with localized amyloidosis
      had pulmonary nodules: Three patients had solitary nodules, one patient had two
      nodules, and one patient had 10 nodules. Nodules ranged in size from 8 mm to 3
      cm. Eight patients with systemic amyloidosis had diffuse lung disease. One
      patient with systemic amyloidosis had recurrent right pleural effusions. Two
      patients with localized amyloidosis had laryngotracheobronchial amyloidosis. One
      of the two patients had focal thickening of the right aryepiglottic fold. The
      other patient had diffuse concentric soft-tissue thickening within the trachea.
      CONCLUSIONS: Localized amyloidosis can occur in patients as pulmonary nodules or
      as laryngotracheobronchia involvement. Nodules are typically solitary (60%) with
      a smooth or lobular contour and are frequently in a subpleural or peripheral
      location. Calcification is not common (20%). Systemic amyloidosis can occur in
      patients as a combination of adenopathy (75%), multiple pulmonary nodules (50%),
      and diffuse irregular lines or interlobular septal thickening (50%).

PMID- 9016205
TI  - Interstitial laser photocoagulation for the treatment of lung cancer.

PMID- 9016206
TI  - Talc pleurodesis simulating pleural metastases on 18F-fluorodeoxyglucose positron
      emission tomography.

PMID- 9016207
TI  - Common carotid artery bifurcation: preliminary results of CT angiography and
      color-coded duplex sonography compared with digital subtraction angiography.
AB  - OBJECTIVE: The purpose of this study was to compare the abilities of color-coded
      duplex sonography, CT angiography, and selective digital subtraction angiography
      to reveal disease requiring surgery in patients with occlusive disease of the
      carotid bifurcation. MATERIALS AND METHODS: Fifty-six carotid arteries in 28
      patients who had 48 carotid stenoses and symptomatic cerebrovascular disease were
      prospectively studied by selective digital subtraction angiography, color-coded
      duplex sonography, and CT angiography. CT data were displayed in maximum
      intensity projection. The degree of stenoses revealed were graded as mild,
      moderate, severe, and occluded according to North American Symptomatic Carotid
      Endarterectomy Trial criteria. The results of CT angiography and color-coded
      duplex sonography were correlated with the gold standard of digital subtraction
      angiography. RESULTS: Grading of stenoses on CT angiography agreed with grading
      of stenoses on digital subtraction angiography in 89% of cases. All high-grade
      stenoses and occlusions revealed on CT angiography were correctly interpreted by
      all observers. For stenoses revealed by color-coded duplex sonography and digital
      subtraction angiography, observers' agreement was 75%. Two severe stenoses were
      incorrectly graded as occluded by the interpreter of the color-coded duplex
      sonograms. Also, one occluded carotid artery was misdiagnosed as moderate
      stenosis. CONCLUSION: Our results indicate that CT angiography is superior to
      color-coded duplex sonography for evaluating carotid disease and determining
      disease requiring surgery. CT angiography warrants further investigation in a
      larger group of patients.

PMID- 9016208
TI  - Myxopapillary ependymoma of the filum terminale.

PMID- 9016209
TI  - Percutaneous fibrin glue therapy of meningeal cysts of the sacral spine.
AB  - OBJECTIVE: We assessed CT-guided percutaneous injection of fibrin glue to manage
      meningeal cysts of the sacral spine in patients with back pain. CONCLUSION: All
      patients experienced resolution or marked improvement of symptoms for as long as
      23 months after fibrin glue therapy. No patients experienced recurrence of
      symptoms during the follow-up interval. Percutaneous CT-guided fibrin glue
      therapy for sacral meningeal cysts may be a more definitive therapy than
      repetitive cyst aspiration.

PMID- 9016210
TI  - CT imaging of mental nerve neuropathy: the numb chin syndrome.

PMID- 9016211
TI  - Rapid lumbar spine MR myelography using rapid acquisition with relaxation
      enhancement.

PMID- 9016212
TI  - MR imaging evaluation with a transrectal surface coil of local recurrence of
      prostatic cancer in men who have undergone radical prostatectomy.
AB  - OBJECTIVE: The objective of this study was to evaluate the ability of transrectal
      surface coil MR imaging to reveal local recurrence of malignancy in men who have
      had radical prostatectomy for prostatic adenocarcinoma. SUBJECTS AND METHODS: We
      performed prospective analysis of 41 men who had undergone radical prostatectomy
      (range of time since surgery, 8 months to 5 years; mean, 26 months), 35 of whom
      had clinical suspicion of recurrent prostatic cancer and the remaining six of
      whom had no clinical evidence of recurrent prostatic cancer (controls). Our
      imaging used a transrectal surface coil on a 1.5-T MR scanner. Sagittal and axial
      fat-saturated T2-weighted fast spin-echo as well as axial T1-weighted unenhanced
      and gadolinium-enhanced MR images of the prostatic bed were acquired in all
      patients. Thirty-one of the 35 men with clinical suspicion of recurrent prostatic
      cancer had elevated prostate-specific antigen (PSA) levels (> or = 0.4 ng/ml),
      and 22 of these 31 men had a palpable prostatic bed module or induration. The
      four of 35 men with clinical suspicion of recurrent prostatic cancer who had PSA
      levels less than 0.4 ng/ml had a palpable prostatic bed nodule or induration.
      Transrectal biopsy of the prostatic bed was directed by digital palpation or
      transrectal sonography in all 35 men with clinical suspicion of recurrent
      malignancy. RESULTS: Thirty-one of the 35 men who had clinical suspicion of local
      recurrence of prostatic cancer had a soft-tissue nodule revealed in the prostatic
      bed by transrectal surface coil MR imaging. Compared with the adjacent muscle,
      all nodules were isointense on the T1-weighted images, hyperintense on the T2
      weighted images, and enhanced with gadolinium administration. The 22 patients who
      had an abnormal MR scan and a palpable nodule or induration and the nine patients
      with elevated PSA levels, no palpable abnormality, and an abnormality revealed by
      MR imaging underwent transrectal biopsy; all had recurrent prostatic cancer
      proven by histology in the four patients with a palpable prostatic bed nodule or
      induration and normal PSA levels, MR imaging showed no distinct soft-tissue
      nodule or area of enhancement in the prostatic bed; transrectal biopsy of the
      palpable nodule or induration yielded fibrosis but no malignancy in all four
      patients. In the six control patients with no clinical evidence of local
      recurrence, MR imaging revealed no evidence of recurrent malignancy; all six
      control patients continue to have no clinical evidence of recurrent prostatic
      cancer with a minimum follow-up of 22 months. Thus, the sensitivity of MR imaging
      in revealing local recurrence of prostatic cancer was 100% (95% confidence
      interval = 89-100%), and the specificity also was 100% (95% confidence interval =
      69-100%). The kappa coefficient was 1.0 (p < .001). CONCLUSION: MR imaging with a
      transrectal surface coil is a useful imaging tool to evaluate men who have
      undergone radical prostatectomy and are suspected of having local recurrence of
      malignancy in the prostatic bed.

PMID- 9016213
TI  - MR urography: evaluation of a three-dimensional fast spin-echo technique in
      patients with hydronephrosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate a respiratory-triggered
      three-dimensional (3D) fast spin-echo technique for MR urography in patients with
      urinary tract dilatation. SUBJECTS AND METHODS: Using a respiratory-triggered 3D
      fast spin-echo technique for MR urography, we obtained MR urograms in 24 patients
      with hydronephrosis. Images were separately reviewed by two radiologists who
      evaluated the images for quality, presence of, degree of, level of, and cause of
      urinary tract dilatation. Findings were compared with all available clinical,
      imaging, surgical, and pathologic data, which served as the standard of
      reference. Sensitivity, specificity, positive predictive value, and negative
      predictive value of MR urograms were calculated for each reviewer to reveal
      urinary tract dilatation. For each reviewer, we calculated agreement between MR
      urography and the standard of reference using kappa analysis. We also calculated
      interobserver agreement for the presence of degree of, level of, and cause of
      urinary tract dilatation. RESULTS: Technically adequate MR urograms were obtained
      in all patients. For detection of urinary tract dilatation by MR urography, the
      sensitivity was 100%; specificity was 96%; positive predictive value was 96%; and
      negative predictive value was 100%. The kappa values for the degree of dilatation
      seen on the MR urograms were 0.57 (moderate) and 0.43 (moderate); for the level
      of obstruction, 0.74 (substantial) and 0.55 (moderate); and for the cause of
      obstruction, 0.66 (moderate) and 0.66 (moderate). Interobserver agreement for
      seeing dilatation on MR urograms was 1.0 (perfect agreement); degree of
      dilatation, 0.48 (moderate); level of dilatation, 0.60 (moderate); and cause of
      dilatation, 0.74 (substantial). CONCLUSION: MR urography using a respiratory
      triggered 3D fast spin-echo technique can produce high-resolution images of the
      urinary tract by which reviewers can achieve a high sensitivity (100%) and
      specificity (96%) for the detection of urinary tract dilatation. On MR urograms,
      reviewers also identified the cause of obstruction in most patients: 92%
      (reviewer 1) and 88% (reviewer 2).

PMID- 9016214
TI  - Invasion of the urinary bladder by uterine cervical carcinoma: evaluation with MR
      imaging.
AB  - OBJECTIVE: This study was performed to assess the accuracy of MR imaging in
      revealing invasion of the urinary bladder by uterine cervical carcinoma. SUBJECTS
      AND METHODS: Vesical invasion was evaluated in 300 consecutive patients who
      underwent MR imaging for preoperative staging of uterine cervical carcinoma. MR
      imaging was obtained with a 0.5-T unit using spin-echo T1- and T2-weighted
      images. Contrast-enhanced T1-weighted images were also obtained in 199 patients.
      MR imaging findings were compared with surgical or cystoscopic findings. MR
      images were then reevaluated in all cases to detect any additional MR imaging
      findings suggestive of vesical invasion. RESULTS: Among the 300 patients, vesical
      invasion was present in 12 patients. For detecting vesical invasion, MR imaging
      had a sensitivity of 83%, a specificity of 100%, and an accuracy of 99% (10 true
      positives, 288-negatives, no false-positives, and two false-negatives). MR
      imaging findings that suggested vesical invasion were nodularity and irregularity
      of the bladder wall (n = 5), masses protruding into the bladder lumen (n = 2),
      and high signal intensity of the anterior aspect of the posterior wall of the
      bladder (n = 7). In addition, we saw abnormal soft-tissue strands in the
      uterovesical space in the two false-negative cases. On reevaluation of the MR
      images in the true-negative cases, we did not see nodularity or irregularity of
      the bladder wall, masses protruding into the bladder lumen, high signal intensity
      of the anterior aspect of the posterior wall of the bladder, or soft-tissue
      strands in the uterovesical space. CONCLUSION: Familiarity with the MR imaging
      findings that we have described may prove helpful before surgery in detecting
      vesical invasion by cervical carcinoma.

PMID- 9016215
TI  - MR imaging evaluation of benign mesenchymal tumors of the urinary bladder.

PMID- 9016216
TI  - Unenhanced helical CT for suspected acute appendicitis.
AB  - OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of
      unenhanced helical CT scans in patients with a suspected acute appendicitis.
      SUBJECTS AND METHODS: Over a 20-month period, 109 adult patients with suspected
      acute appendicitis were referred by the emergency department for an unenhanced
      helical CT scan. Each scan was obtained in a single breath-hold from the T12
      vertebral body to the public symphysis using a 5-mm collimation and a pitch of
      1.6. No patients were given oral or IV contrast media. The primary CT criteria
      for diagnosing acute appendicitis was the identification of an appendix with a
      transverse diameter larger than 6 mm with associated periappendiceal inflammatory
      changes. The presence of an appendicolith was considered a secondary finding as
      was isolated periappendiceal inflammation; however, appendicitis was not
      diagnosed in such patients unless an enlarged appendix was definitely identified.
      Final diagnoses were established by surgical or clinical follow-up and were
      compared with the original CT reports. RESULTS: We found 66 true-negatives, 37
      true-positives, four false-negatives, and two false-positives that yielded a
      sensitivity of 90%, a specificity of 97%, a positive predictive value of 95%, a
      negative predictive value of 95%, and an accuracy of 94%. An alternative
      diagnosis was established by an unenhanced helical CT scan in 24 patients (22%),
      which included cecal diverticulitis (seven patients), urinary tract disease (five
      patients), adnexal pathology (four patients), sigmoid diverticulitis (two
      patients), small bowel disease (three patients), right lower quadrant tumor (two
      patients), and an infected dialysis catheter (one patient). CONCLUSION:
      Unenhanced thin-section helical CT is an accurate, effective technique for
      diagnosing acute appendicitis.

PMID- 9016217
TI  - CT Imaging of acute right lower quadrant disease.

PMID- 9016218
TI  - Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission
      tomography.
AB  - OBJECTIVE: The objective of this study was to assess the performance of positron
      emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in the staging of
      cancer in patients with esophageal carcinoma. MATERIALS AND METHODS: The findings
      of FDG PET and of CT in the chest and upper abdomen of 36 patients with newly
      diagnosed esophageal carcinoma were compared with pathologic findings obtained
      either during a curative surgical procedure with tissue sampling (n = 29) or by
      tissue sampling alone (n = 7). RESULTS: Abnormal FDG uptake was identified on PET
      in the esophageal tumors of all patients. In 29 patients who underwent curative
      esophagectomy, PET and CT accurately revealed the extent of nodal disease in 76%
      (22/29) and 45% (13/29) of patients, respectively. In the seven patients who
      underwent tissue sampling instead of complete esophagectomy, PET revealed
      metastatic disease in five patients, all of whom avoided needless surgery. CT
      failed to reveal metastatic disease in these five patients. In addition, PET
      incidentally revealed an unsuspected primary long carcinoma in one patient.
      CONCLUSION: FDG PET is more sensitive than CT for revealing regional and distant
      metastases in patients with esophageal carcinoma. The use of PET in the staging
      of esophageal cancer may prove to be cost-effective by decreasing the number of
      unnecessary surgeries in patients with unresectable tumors.

PMID- 9016219
TI  - CT findings of mesenteric injury after blunt trauma: implications for surgical
      intervention.
AB  - OBJECTIVE: The purposes of this study were to determine the spectrum of CT
      findings of mesenteric injury, to compare CT findings of mesenteric injury with
      surgical observations, and to assess the potential of CT to predict which
      patients with mesenteric injury require laparotomy. MATERIALS AND METHODS: Blunt
      trauma patients admitted to our facility during a 5-year 4-month period with a CT
      or surgical diagnosis of mesenteric injury were identified from a radiology
      database and trauma registry. Patients with CT findings of full-thickness bowel
      injury associated with mesenteric injury or diagnostic peritoneal lavage
      performed before CT were excluded. CT scans of all patients were retrospectively
      reviewed both with and without knowledge of surgical results. Medical records of
      all study patients were reviewed to ascertain admission physical findings and
      surgical results. RESULTS: Twenty-seven of 29 patients meeting the study criteria
      underwent laparotomy, and two others were managed conservatively. Among the 27
      patients who had surgery. 24 (89%) had CT findings of mesenteric injury
      confirmed. Surgical findings showed CT scans to be falsely negative in two other
      patients and falsely positive in one other patient. No major discrepancies were
      found between retrospective CT review done with and without knowledge of the
      surgical findings. Two CT findings unique to patients whose injuries, in the
      judgment of the surgical team, required surgical repair were active extravasation
      of IV contrast material and bowel wall thickening associated with mesenteric
      findings. Physical findings did not correlate well with the type and clinical
      significance of the mesenteric injury. CONCLUSION: The CT finding of mesenteric
      bleeding or bowel wall thickening associated with mesenteric hematoma or
      infiltration in the blunt trauma patient indicates a high likelihood of a
      mesenteric or bowel injury requiring surgery. The finding of focal mesenteric
      hematoma or infiltration without adjacent bowel wall thickening is nonspecific
      and can occur both in mesenteric or bowel lesions that require surgery and those
      that do not.

PMID- 9016220
TI  - Doppler sonography evaluation of superior mesenteric artery flow to assess
      Crohn's disease activity: correlation with clinical evaluation, Crohn's disease
      activity index, and alpha 1-antitrypsin clearance in feces.
AB  - OBJECTIVE: This study was undertaken to investigate the value of Doppler flow
      measurements of the superior mesenteric artery (SMA) as a marker for disease
      activity in patients with Crohn's disease. SUBJECTS AND METHODS: Duplex Doppler
      sonography measurements of SMA blood flow volume were obtained in 29 consecutive
      patients with suspected Crohn's disease. We prospectively sought a correlation
      between the independent assessment of Doppler flow measurements and markers for
      disease activity: Crohn's disease activity index and fecal alpha 1-antitrypsin
      clearance and our reference standard based on clinical history, physical
      examination, laboratory values, endoscopy, surgery, and follow-up. RESULTS: In 27
      of 29 patients, adequate measurements of SMA blood flow were obtained. In 15
      patients no disease activity was judged to be present or no Crohn's disease (n =
      2) was found at follow-up (group 1). In 12 patients, activity of Crohn's disease
      was diagnosed (group 2) on the basis of the reference standard. In group 2 the
      Doppler SMA blood flow values were significantly higher (p < .05) than those for
      group 1 (826 +/- 407 ml/min versus 323 +/- 103 ml/min). Of the other parameters
      investigated, only the alpha 1-antitrypsin value correlated with the reference
      standard but to a lesser degree than the values for SMA blood flow measurement.
      CONCLUSION: This prospective study shows that SMA Doppler blood flow measurements
      can be used to assess disease activity in patients with Crohn's disease. This
      approach may be of value in the diagnosis and follow-up of patients with Crohn's
      disease, providing directly available, quantifiable, noninvasive information on
      disease activity.

PMID- 9016221
TI  - Mesenteric small-bowel polyposis: a diagnostic radiographic sign of
      neurofibromatosis.

PMID- 9016222
TI  - Using biphasic CT to reveal gastrointestinal arteriovenous malformations.

PMID- 9016223
TI  - CT appearance of acute appendicitis in childhood.

PMID- 9016224
TI  - Esophageal foreign bodies: safety and efficacy of Foley catheter extraction of
      coins.
AB  - OBJECTIVE: Continued controversy over the role of fluoroscopically guided Foley
      catheter removal of esophageal foreign bodies has limited the use of this
      technique despite its significant economic advantages. We reviewed our experience
      for the safety, efficacy, and applicability of this technique with pediatric
      patients who had swallowed coins. MATERIALS AND METHODS: We retrospectively
      reviewed 10 years of experience with pediatric patients who had undergone
      fluoroscopically guided Foley catheter removal of coins. All the pediatric
      patients with a suspected esophageal foreign body were first evaluated by plain
      film radiography. Foley catheter extraction was attempted when a radiopaque coin
      was seen and the patient lacked signs of significant esophageal edema resulting
      in tracheal compromise. During the 10 years covered by our review, 14 pediatric
      radiologists with specific training in the Foley catheter technique were involved
      in such removals. A separate review (of consecutive pediatric patients who had a
      history of or symptoms suggesting ingestion of a foreign body) focused on the
      percentage of these patients in which the Foley catheter technique was used.
      RESULTS: Of the 337 coin extractions attempted using a Foley catheter, coin
      extraction was successful in 322 (96%) of 337 patients. No complications were
      encountered. Our focused review found 422 consecutive patients who had undergone
      radiography to rule out foreign bodies. A radiopaque object was found in 249
      (59%) of 422 patients. Of these 249 objects, 208 (84%) were ingested coins. Of
      208 coins, 123 (59%) were retained in the esophagus; of these 123 coins retained
      in the esophagus, 116 (94%) were amenable to fluoroscopically guided Foley
      catheter extraction. CONCLUSION: Fluoroscopically guided Foley catheter
      extraction of retained coins in pediatric patients who lack evidence of
      significant esophageal edema causing tracheal compromise is a safe and
      efficacious technique. It should be considered the technique of choice for such
      extractions.

PMID- 9016225
TI  - Rhabdoid tumor of the kidney in children: a comparative study of 21 cases.
AB  - OBJECTIVE: Rhabdoid tumor of the kidney (RTK) is unique among childhood renal
      neoplasms in its frequent association with primary or metastatic CNS lesions.
      Previous reports suggest that RTK has characteristic CT features. It has been
      proposed that if CT could accurately predict the correct diagnosis of RTK
      preoperatively, then imaging protocols might be modified during the examination
      to include imaging of the brain. We wished to determine if RTK could be reliably
      distinguished from other renal neoplasms of early childhood. MATERIALS AND
      METHODS: We retrospectively reviewed clinical, radiologic, and pathologic records
      of 21 patients with RTK. The study group included 13 males and eight females who
      were newborn to 36 months old (mean, 11 months). The study group was compared
      with 153 patients who were 3 years old or younger and who had solid renal masses.
      From the comparison group a subset of 54 patients 1 year old and younger was also
      selected for comparison with 13 (62%) of the 21 patients in the study group who
      were 1 year old or younger. Both comparison groups consisted of patients whose
      case material was consecutively added to the radiologic pathology archives at our
      institution. Diagnoses of the group of 153 patients were Wilms' tumor (n = 93),
      mesoblastic nephroma (n = 44), clear cell sarcoma of the kidney (n = 12), renal
      cell carcinoma (n = 3), and undifferentiated sarcoma (n = 1). RESULTS: A
      prominent eccentric crescent with the attenuation of fluid, representing sub
      capsular renal hemorrhage or peripheral tumor necrosis adjacent to tumor lobules,
      was revealed on CT scans in 15 (71%) of the 21 patients with RTK and in seven
      (54%) of the 13 patients with RTK who were 1 year old or younger. Nineteen (12%)
      of 153 patients in the larger comparison group, representing patients with all
      tumor types, had CT features identical to those of the RTK group, including six
      (4%) patients with pathologic confirmation of sub-capsular renal hematomas. Six
      (11%) of the 54 comparison patients 1 year old and younger had CT features
      identical to those of the RTK group, and all proved to have mesoblastic nephroma.
      Associated CNS lesions were seen on CT or MR imaging in 11 (52%) of the 21
      patients with RTK but none was seen in the comparison group of patients.
      CONCLUSION: On CT, a peripheral crescent with the attenuation of fluid is
      characteristic of RTK. However, 12% of renal neoplasms that occur more commonly
      than RTK in children had CT findings indistinguishable from those of RTK. Because
      the prevalence of RTK is relatively low, and because the CT findings are not
      pathognomonic, a renal mass seen on CT in a child is unlikely to represent RTK
      regardless of its CT features. We therefore conclude that the routine addition of
      CT of the brain for pediatric patients with renal masses that show a peripheral
      crescent of fluid attenuation is not justified. Supplemental imaging of the brain
      should be based on clinical findings or tissue diagnosis.

PMID- 9016226
TI  - Imaging findings of pancreaticobiliary duct diseases with single-shot MR
      cholangiopancreatography.

PMID- 9016227
TI  - Hepatic cavernous hemangioma: appearance on T2-weighted fast spin-echo MR imaging
      with and without fat suppression.
AB  - OBJECTIVE: The goals of our study were to define the morphologic appearance of
      cavernous hemangioma of the liver on T2-weighted fast spin-echo MR imaging and to
      determine if the use of fat suppression may quantitatively and qualitatively
      modify the MR imaging appearance of cavernous hemangioma. SUBJECTS AND METHODS:
      Twenty-six patients with cavernous hemangiomas of the liver were prospectively
      studied with T2-weighted MR imaging with a fast spin-echo technique with and
      without fat suppression. Thirteen patients had known hemangiomas for more than 2
      years, with no change in size or morphology during this period. The remaining 13
      patients had diagnoses based on dynamic CT and sonography and an absence of
      change in the morphology and size of their lesions during follow-up of more than
      6 months (range, 6-12 months) after the MR imaging studies. Values for signal
      intensity and contrast-to-noise (C/N) ratios in cavernous hemangiomas that were
      obtained with and without fat suppression were compared. Images were
      qualitatively analyzed separately at identical level and window settings by two
      interpreters for morphologic features of cavernous hemangiomas. RESULTS: No
      significant difference was found between signal intensity values obtained using
      the fat-suppressed fast spin-echo MR imaging technique (5.62 +/- 1.14 [SD]) and
      those obtained without fat suppression (5.51 +/- 1.23). Values for C/N ratios
      obtained with the fat-suppressed fast spin-echo MR imaging technique (20.13 +/-
      7.63) were significantly superior to those obtained without fat suppression
      (16.59 +/- 5.31) (p < .001). On T2-weighted fast spin-echo MR imaging without fat
      suppression, 100% of cavernous hemangiomas were hyperintense relative to the
      spleen, 90% had well-defined and sharp margins, 55% were isointense to CSF, and
      76% were homogeneous. Without fat suppression, 34% of cavernous hemangiomas
      showed the combination of isointensity to CSF, well-defined margins, and
      homogeneity. On T2-weighted fast spin-echo MR imaging with fat suppression, all
      cavernous hemangiomas showed this same combination of features. CONCLUSION:
      Seventy-six percent of hepatic cavernous hemangiomas were homogeneous on T2
      weighted fast spin-echo MR imaging, and 55% were isointense to CSF. However, only
      34% of hepatic cavernous hemangiomas showed typical features. Although fat
      suppression significantly increased the C/N ratio of cavernous hemangiomas of the
      liver, fat suppression did not affect their morphologic appearance on T2-weighted
      fast spin-echo MR imaging.

PMID- 9016228
TI  - Doppler sonography findings associated with transjugular intrahepatic
      portosystemic shunt malfunction.
AB  - OBJECTIVE: Our purpose was to determine the overall accuracy of Doppler
      sonography and the accuracy of specific Doppler parameters associated with a
      compromised transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND
      METHODS: For 43 patients who had undergone TIPS, 64 correlated sonogram-venogram
      paired examinations were analyzed. Sonographic parameters assessed included
      absolute velocities plus absolute and percentage changes in velocities measured
      in the main portal vein (MPV) and in several intrashunt locations (including peak
      and minimum velocity). Direction of flow and change in direction of flow in the
      left and right portal veins were also examined. TIPS malfunction was defined as
      any shunt with greater than or equal to 50% stenosis or any stenosis with a
      portosystemic gradient greater than 15 mm Hg. RESULTS: The prospective
      interpretation of the sonograms using all available parameters resulted in a
      sensitivity of 92% and a specificity of 72% for detecting TIPS malfunction. Peak
      shunt velocity (absolute velocity and velocity change), distal shunt velocity,
      MPV velocity (absolute velocity and percentage change in velocity), change in
      minimum shunt velocity, and direction of flow in branch portal veins were found
      to have statistically significant differences between normal and abnormal shunts.
      Sensitivities for these individual parameters ranged from 64% to 84%, and
      specificities ranged from 70% to 100%. When either the MPV velocity or the distal
      shunt velocity was abnormal, the sensitivity was 94%. When both parameters were
      abnormal, the specificity for detecting TIPS malfunction was 100%. CONCLUSION:
      Doppler sonography is a sensitive and relatively specific means of revealing TIPS
      malfunction. Accuracy depends on analysis of multiple sonographic parameters.

PMID- 9016229
TI  - Use of Doppler sonography for revealing hepatic artery stenosis in liver
      transplant recipients.
AB  - OBJECTIVE: The goal of our study was to evaluate the use of duplex Doppler
      sonography for revealing hepatic artery stenosis (HAS) in patients who have
      undergone liver transplantation. MATERIALS AND METHODS: Forty-six patients with
      spectral Doppler waveforms obtained from the hepatic artery and with subsequent
      arteriography were reviewed retrospectively. Arterial waveforms, resistive
      indexes (RIs), and systolic acceleration times (SATs) were evaluated by one
      reviewer who was unaware of the arteriographic findings. The mean interval
      between the two examinations was 2.8 days. Arteriograms that revealed a stenosis
      of greater than 50% were classified as abnormal. RESULTS: Of the 46 patients, 21
      (46%) had a significant stenosis. Patients who had HAS had significantly (p <
      .05) prolonged SATs (0.08 +/- 0.03 sec versus 0.06 +/- 0.02 sec) and reduced RIs
      (0.49 +/- 0.05 versus 0.66 +/- 0.05) compared with patients who did not have HAS.
      Optimal thresholds for HAS detection were RIs less than 0.55 and SATs greater
      than 0.08 sec. HAS was found in 14 of 15 patients who had both abnormal RIs and
      SATs. Of the remaining 31 patients, 12 had abnormal values for RI or SAT. Of
      these 12 patients, three had HAS. Thus, 19 patients had normal RIs and SATs;
      however, four of these patients were found to have an arterial stenosis. In our
      46 patients, abnormal values for both RI and SAT were 67% sensitive and 96%
      specific for stenosis. When at least one abnormal value was found on Doppler
      imaging, sensitivity and specificity for stenosis were 81% and 60%, respectively.
      CONCLUSION: Duplex Doppler imaging can noninvasively reveal HAS. Abnormal values
      for both RI and SAT proved to be a more accurate predictor of stenosis than
      either RI or SAT as independent parameters.

PMID- 9016230
TI  - Suprahepatic caval anastomotic stenosis complicating orthotopic liver
      transplantation: treatment with percutaneous transluminal angioplasty, Wallstent
      placement, or both.
AB  - OBJECTIVE: Our objective was to evaluate, over a 5-year period, the nonsurgical
      treatment of three patients with suprahepatic caval anastomotic stenosis who had
      undergone orthotopic liver transplantation. CONCLUSION: Balloon angioplasty is a
      safe and effective method for treating chronic caval stenosis occurring in
      patients who have undergone orthotopic liver transplantation. Caval stenosis
      identified in the early postoperative period, especially when such stenosis is
      associated with caval torsion or kinking, may be effectively treated by stent
      placement.

PMID- 9016231
TI  - The aberrant subclavian artery.

PMID- 9016232
TI  - Detection with MR imaging of residual tumor in the breast soon after surgery.
AB  - OBJECTIVE: Difficulties in the preoperative assessment of tumor size and extent
      result in a positive pathologic margin in up to 70% of patients undergoing breast
      conservation surgery. Although positive margins usually require reexcision, the
      location and extent of surgery required are often difficult to establish by
      current imaging techniques. We investigated the accuracy of three-dimensional
      rotating delivery of excitation off resonance (3D RODEO) MR imaging of the breast
      in revealing the presence and extent of residual tumor within the breast soon
      after surgery. MATERIALS AND METHODS: Nineteen patients who had undergone
      lumpectomy or excisional biopsy were evaluated with contrast-enhanced 3D RODEO MR
      imaging of the breast within 10 months after surgery. The MR imaging results were
      correlated with serial-sectioned mastectomy or partial mastectomy specimens from
      18 patients and with a clinical and mammographic follow-up examination in one
      patient. RESULTS: We found that 3D RODEO MR imaging accurately revealed the
      presence or absence and the location and extent of recurrent tumor in 15 of the
      18 patients who had pathologic confirmation. Of the three MR imaging-pathology
      mismatches, two had irregular or nodular enhancement that corresponded to
      microabscesses. The third mismatch showed multicentric disease on MR imaging but
      only single-quadrant lobular carcinoma at pathologic examination. Our 19th
      patient showed no evidence of recurrent tumor on MR imaging or at 2-year follow
      up clinical and mammographic examinations. CONCLUSION: MR imaging with 3D RODEO
      technique correctly revealed the presence or absence, the location, and the
      extent of recurrent tumor in 84% of patients who had recently undergone breast
      surgery.

PMID- 9016233
TI  - Mammographic features of local recurrence in women who have undergone breast
      conserving therapy for ductal carcinoma in situ.
AB  - OBJECTIVE: This study was undertaken to evaluate the mammographic features of
      local recurrence in women who have undergone breast-conserving therapy for ductal
      carcinoma in situ (DCIS). MATERIALS AND METHODS: Retrospective review revealed
      162 women with DCIS treated with breast-conserving therapy from 1978 to 1990 for
      whom follow-up data were available. Subsequent to therapy, 33 (20%) patients had
      a pathologically proven carcinoma in the treated breast. Mammograms at the time
      of local recurrence were available for 20 patients. We reviewed mammograms,
      clinical charts, and histopathologic findings in these 20 patients. For 14 of 20
      patients, we also reviewed mammograms obtained at the time of the original DCIS.
      RESULTS: The median interval from diagnosis of the original DCIS to local
      recurrence was 26 months (range, 6-168 months). Recurrences were detected solely
      by mammography in 17 (85%) of 20 patients, by mammography and physical
      examination in two (10%), and solely by physical examination in one (5%).
      Eighteen (90%) local recurrence contained calcifications and eighteen (90%)
      involved the tumorectomy quadrant. When we compared available mammographic
      findings of the original DCIS and the local recurrence we found the mammographic
      pattern and calcification morphology to be the same in 11 (79%) of 14 DCIS and
      nine (82%) of 11 DCIS, respectively. Histopathologic analysis of recurrences
      found DCIS in 13 (65%) of 20 patients and DCIS and infiltrating carcinoma in the
      remaining seven (35%) patients. Of 13 pure DCIS recurrences, 12 (92%) were
      detected solely by mammography. CONCLUSION: In our study, local recurrence after
      breast-conserving therapy for DCIS invariably contained DCIS; 35% of recurrences
      also contained invasive carcinoma. The most common mammographic pattern of local
      recurrence was calcifications in the tumorectomy quadrant that were
      morphologically similar to the original DCIS. These findings suggest that many of
      these local recurrences reflect failure to eradicate the primary DCIS.
      Mammography achieved high sensitivity in revealing these lesions: 85% of local
      recurrences and 92% of recurrences that were pure DCIS were detected solely by
      mammography.

PMID- 9016234
TI  - Impact of core biopsy on the surgical management of impalpable breast cancer.
AB  - OBJECTIVE: The purpose of this study was to compare impalpable breast carcinomas
      revealed by core biopsy with those revealed by surgical biopsy with respect to
      the frequency of performing a single surgical procedure and finding tumor at the
      margins of the lumpectomy specimen. MATERIALS AND METHODS: Retrospective review
      found 197 solitary impalpable breast carcinomas revealed by core biopsy using a
      14-gauge needle (n = 90) or surgical biopsy after needle localization (n = 107).
      Lumpectomy was the surgical treatment in 62 (69%) of the 90 cancers revealed by
      core biopsy and in 74 (69%) of the 107 cancers revealed by surgical biopsy.
      Records were reviewed to determine the number and type of surgeries performed on
      each patient and the histopathologic findings at surgery. Lumpectomy margins were
      considered positive if tumor was present at the inked margins of a lumpectomy
      performed as a separate procedure after the diagnostic biopsy. RESULTS: A single
      surgical procedure was performed 76 (84%) of the 90 patients who underwent core
      biopsy versus 31 (29%) of the 107 patients who underwent surgical biopsy. This
      difference was statistically significant (p < .00001). Tumor was present at the
      lumpectomy margins in five (8%) of the 62 cancers revealed by core biopsy versus
      four (5%) of the 74 cancers diagnosed by surgical biopsy. This difference was not
      statistically significant (p = .7). CONCLUSION: A single surgical procedure was
      performed significantly more often in patients in whom impalpable breast cancer
      was revealed by core biopsy. The likelihood of obtaining tumor-free margins at
      lumpectomy did not differ significantly for cancers revealed by either method.
      These data indicate that core biopsy provides the information necessary to plan
      surgical treatment and could decrease the number of surgical procedures required
      in patients with impalpable breast cancer.

PMID- 9016236
TI  - Fixed-facility workplace screening mammography.
AB  - OBJECTIVE: Potential barriers to compliance with screening mammography guidelines
      include the cost and inconvenience involved with undergoing the procedure.
      Workplace screening with mobile mammography is one possible approach to the
      convenience barrier. However, fixed-facility workplace screening is a viable
      alternative for any company with a large workforce in one location. This paper
      describes our initial experience with one such fixed facility. MATERIALS AND
      METHODS: The facility was a cooperative venture by a large pharmaceutical company
      and an academic radiology department to provide convenient, no-cost (to the
      patient) screening mammography to employees, dependents, and retirees more than
      40 years old. The pharmaceutical company built the facility within its corporate
      headquarters and the academic radiology department provided the equipment and
      personnel. The company was billed a fixed cost per examination. RESULTS: In the
      first 22 months of operation, 4210 (of 4559 scheduled) screening mammograms were
      obtained. The mean age of the population was 53 years old. Ninety percent of the
      screening mammograms were interpreted as negative or benign; 10% required
      additional workup. Of the screened population, 62 biopsies were recommended and
      60 were performed. Of these, 42 were benign and 18 malignant. The cancer
      detection rate was 4.3 per 1000 (0.43%). At the time of diagnosis, six patients
      were stage 0, 10 patients were stage I, one patient was stage II, and one patient
      was stage III. Eleven of the 18 patients had minimal cancers. Of the patients who
      completed a satisfaction survey, 97% percent expressed a high degree of
      satisfaction with the screening process and stated they would use the facility in
      the future. CONCLUSION: A fixed facility for workplace screening mammography is a
      viable way to provide nearly barrier-free access to high-quality mammography.
      Patient acceptance is high.

PMID- 9016235
TI  - Fatty and fibroglandular tissue volumes in the breasts of women 20-83 years old:
      comparison of X-ray mammography and computer-assisted MR imaging.
AB  - OBJECTIVE: A method for segmenting MR images of the breast was applied to
      determine fatty and fibroglandular tissue volumes in breasts of women in
      different age groups. The results were compared with subjective assessments of
      breast density from X-ray mammograms in the same patients. MATERIALS AND METHODS:
      Two experienced mammographers assessed the percentage of fat in the breasts of 40
      women who were 20-83 years old. MR images were obtained on a 1.0-T scanner
      equipped with a bilateral receive-only breast coil. Images were acquired using a
      three-dimensional T1-weighted gradient-echo sequence with a 1.25 x 1.4 x 2.5 mm
      resolution. On average, breast parenchyma appeared in 30 images in each breast.
      Image segmentation was based on a semiautomated, two-compartmental (fatty and
      fibroglandular tissue) model that accounts for partial volume effects. To
      validate the accuracy of the MR imaging segmentation technique, we performed a
      phantom study using an identical imaging sequence. RESULTS: The accuracy of the
      MR imaging segmentation of the phantom was of the order of 2%. In our subjects,
      fat content was 42.5% +/- 30.3% (mean +/- SD) on mammography versus 66.5% +/- 18%
      on MR images. Although we found a significant correlation (r = .63) between the
      two techniques, mammography poorly differentiated breasts containing less than
      45% fat. When our analysis included only dense breasts (i.e., those containing
      less than 75% fat on MR images), the correlation coefficient decreased to .34.
      The largest discrepancies between mammography and MR imaging occurred in breasts
      that had 60-80% fat as measured on MR imaging. CONCLUSION: Fatty and
      fibroglandular tissue can be differentiated on MR images of the breast with high
      precision and accuracy, therefore allowing assessment of breast density. The
      conclusions of researchers who used mammographic density patterns should be
      reassessed.

PMID- 9016237
TI  - Mammographic and sonographic findings in metastatic transitional cell carcinoma
      of the breast.

PMID- 9016238
TI  - MR imaging of the fetus by a HASTE sequence.
AB  - OBJECTIVE: The value of a half-Fourier acquisition single-shot turbo spin-echo
      (HASTE) sequence, in which high-resolution heavily T2-weighted images can be
      obtained within 2 sec, was evaluated in the imaging of the fetus during the
      second or third trimester. MATERIALS AND METHODS: Eighteen women with complicated
      pregnancies as revealed on a sonogram during the second and third trimesters (16
      36 weeks' gestation) were studied with a 1.5-T superconductive MR imaging unit
      that used a body phased-array coil. After informed consent, T1-weighted fast low
      angle shot images, T2-weighted turbo spin-echo images, and HASTE images were
      obtained without any premedication. Images were analyzed with regard to image
      quality, degree of blurring, visualization of the normal fetal organs, and
      visualization of fetal and maternal abnormalities. RESULTS: On HASTE sequences,
      visualization of the fetal brain, visceral organs (lung, heart, liver, kidney,
      and bladder), extremities, and umbilical cord were significantly better than on
      fast low-angle shot or turbo spin-echo sequences (p < .01). In the brain, the
      white matter-gray matter distinction, gyrus formation, and myelination of the
      brain were clearly revealed by the HASTE sequence. Pathologic processes including
      fetal abnormalities (anomalies of the central nervous systems [n = 5], placenta
      previa [n = 1], and transverse lie in the third trimester [n = 1]) and maternal
      abnormalities (leiomyoma [n = 5], ovarian tumors [n = 3], and hydronephrosis [n =
      1]) were clearly seen on HASTE imaging. The peak specific absorption rate for RF
      exposure in these studies was less than 1.5 W/kg. CONCLUSION: In situations when
      sonography is suggestive but not definitive, MR imaging with a HASTE sequence
      allows clear fetal imaging with high T2-weighted contrast.

PMID- 9016239
TI  - Prenatal diagnosis of Beckwith-Wiedemann syndrome.

PMID- 9016240
TI  - MR imaging of tophaceous gout.
AB  - OBJECTIVE: MR imaging is not routinely used for evaluation of tophaceous gout.
      However, gout may present clinically in an atypical, unusual, or confusing
      manner. A gouty tophus occasionally mimics an infectious or neoplastic process,
      and MR imaging may be obtained under these circumstances. The purpose of this
      study was to determine the MR imaging characteristics of intraosseous and soft
      tissue tophi. MATERIALS AND METHODS: We identified 13 MR imaging examinations
      performed during a 27-month period on nine patients with gouty arthritis. All
      were men 42-70 years old. T1-, proton density-, and T2-weighted spin-echo MR
      images were obtained for all the examinations. Nine examinations included
      contrast-enhanced MR images. The findings were then evaluated, as were the
      corresponding radiographs. RESULTS: Five patients presented with articular
      involvement, three patients with an isolated soft-tissue mass, and one patient
      with persistent soft-tissue swelling. The duration of symptoms ranged from 3
      months to more than 20 years. Nearly all the tophi were of intermediate signal
      intensity on T1-weighted images. On T2-weighted images, three sites revealed an
      overall increase in the signal intensity of the tophi, whereas 10 studies showed
      a heterogeneous decrease in signal intensity. All but one tophus showed
      homogeneous enhancement. Erosion of adjacent bone, synovial pannus, joint
      effusion, soft-tissue edema, and bone marrow edema were common associated
      findings. CONCLUSION: The MR appearance of tophi in patients with tophaceous gout
      is constant on T1- but quite variable on T2-weighted images. This variability in
      signal intensity could be related to calcium within a tophus. Tophaceous gout
      should be considered in the differential diagnosis when a mass reveals
      heterogeneously low to intermediate signal intensity, particularly if the
      adjacent bone shows typical erosive changes or if other joints are involved. When
      faced with this situation, radiologists may find it helpful to obtain a further
      clinical history and recommend evaluating the patient's serum urate level.

PMID- 9016241
TI  - Efficacy of MR imaging in patients suspected of having Morton's neuroma.
AB  - OBJECTIVE: The purpose of our study was to evaluate the role of MR imaging in
      patients with suspected Morton's neuroma and to assess the value of various MR
      sequences in this diagnosis. MATERIALS AND METHODS: Thirty-two consecutive
      patients with suspected Morton's neuroma were studied using a 1.0-T MR scanner.
      Axial T1- and T2-weighted spin-echo, short inversion time inversion recovery, and
      enhanced T1-weighted fat-suppressed spin-echo images were obtained on each
      patient. Eighteen intermetatarsal spaces in 16 of the 32 patients were evaluated
      surgically. Contrast-to-noise ratios for Morton's neuroma versus surrounding fat
      were calculated and standardized for imaging times. RESULTS: In 15 of 18
      intermetatarsal spaces, a Morton's neuroma was surgically proven. Thirteen true
      positive, two false-negative, three true-negative, and no false-positive MR
      diagnoses were given. In six of 15 proven neuromas, the clinical examiner was not
      able to identify the correct intermetatarsal space. The MR diagnoses in the 16
      remaining patients who did not undergo surgery were Morton's neuroma (n = 8),
      stress fracture (n = 1), foreign body reaction (n = 1), tendon sheath ganglion (n
      = 1), postoperative changes (n = 2), and no abnormality (n = 3). Standardized
      contrast-to-noise ratios (+/- SD) were 2.42 +/- 0.72 for T1-weighted images; 1.43
      +/- 1.13 for T2-weighted images; 1.26 +/- 1.47 for short inversion time inversion
      recovery images; and 0.83 +/- 0.59 gadolinium-enhanced fat-suppressed images. The
      differences were statistically significant for the T1-weighted spin-echo images
      versus the three other sequences (p = .001-.018), but not among the other
      sequences (p = .209-.710). CONCLUSION: MR imaging is accurate in diagnosing
      Morton's neuroma and may be important for correct localization. A limited
      examination employing axial T1-weighted spin-echo images is adequate; additional
      sequences should be employed only for differential diagnosis.

PMID- 9016242
TI  - Dynamic high-resolution sonography of the carpal tunnel.
AB  - CTS is an increasingly common condition with symptoms resulting from compression
      of the median nerve. Although most cases are clinically straightforward, those
      with confusing clinical pictures or equivocal or contradictory diagnostic studies
      may benefit from imaging. Although MR imaging has been established as a useful
      imaging technique for the evaluation of CTS, sonography may be a low-cost
      alternative. Imaging criteria for the diagnosis of CTS apply to both sonography
      and MR imaging. Sonographic evaluation of a large series of patients is still
      necessary to determine the definitive role of sonography in CTS.

PMID- 9016243
TI  - Screen-film versus computed radiography imaging of the hand: a direct comparison.
AB  - OBJECTIVE: Computed radiography of the musculoskeletal system has the potential
      to become a powerful tool in the practice of diagnostic radiology. It addresses
      many of the geographic and film-distribution concerns facing diagnostic imaging.
      We undertook this study to compare and document the quality of computed
      radiographs and conventional screen-film images before widespread implementation.
      MATERIALS AND METHODS: We evaluated clinical images using direct comparison.
      Bilateral hand images from 50 patients were scored independently by six
      musculoskeletal radiologists. In each case one hand was imaged with a
      conventional screen-film technique and the other with computed radiography.
      Images were masked to eliminate as much bias as possible. The numeric scores
      assigned to the images by the observers were analyzed using Student's t test.
      RESULTS: Computed radiographs were judged with statistical significance to be
      better than conventional screen-film images in all features judged by the
      observers, including bone cortex, bone trabeculae, corticomedullary junction,
      distal phalangeal tuft, soft tissues, fat planes, bone-soft-tissue interface, and
      overall contrast and density. CONCLUSION: The statistically significant
      determination that the image quality of computed radiographs is at least as good
      as screen-film images allows confident use of computed radiography and enables
      radiologists to take advantage of its many other practical capabilities related
      to image distribution, storage, cost, and geographic coverage without sacrificing
      image quality.

PMID- 9016244
TI  - Massive bone allografts for limb salvage.

PMID- 9016245
TI  - MR imaging truncation artifacts can create a false laminar appearance in
      cartilage.
AB  - OBJECTIVE: The purpose of this study was to investigate the laminar appearance of
      cartilage on MR images. MATERIALS AND METHODS: Theoretical modeling of truncation
      artifacts was used to predict spatial patterns and associated intensity
      variations in MR imaging. A numerical simulation of a ring model was used to show
      truncation artifacts as a function of the angle in the image plane for unequal in
      plane resolutions. MR imaging of 10 cadaveric human patellae at several
      resolutions used an imaging protocol that produced high-contrast images of
      cartilage. The high-resolution image of each MR imaging set was reduced in
      resolution by low-pass filtering and compared with the acquired images of
      equivalent resolution. Variable-resolution images of the patella of a healthy
      human volunteer were also acquired. RESULTS: Truncation artifacts from opposing
      cartilage edges can create false laminae and artifactual intensities. The
      resulting geometric variations can alter the apparent width of the cartilage as
      well. The intensity variations produced by truncation artifacts can be as much as
      22% of the actual intensity. The most pronounced artifactual trilaminar
      appearance occurs when cartilage thickness exceeds the image resolution by a
      factor of 4. Truncation artifacts vary as a function of the angle in the imaging
      plane for unequal resolutions in the two directions. CONCLUSION: Truncation
      artifacts can produce an artifactual laminar appearance in cartilage and alter
      the apparent cartilage width.

PMID- 9016246
TI  - MR imaging of skeletal muscle metastases.
AB  - OBJECTIVE: The purpose of this article is to describe the MR imaging appearance
      of skeletal muscle metastases. CONCLUSION: Skeletal muscle metastasis must be
      considered in patients with a known primary carcinoma who present with a painful
      muscle mass. Muscle metastasis may be the initial presentation of carcinoma. The
      MR imaging appearance, although not specific, may provide clues to the diagnosis.

PMID- 9016247
TI  - Knee dislocation with suspected popliteal artery disruption.

PMID- 9016248
TI  - MR imaging of the shoulder after rotator cuff repair.

PMID- 9016249
TI  - Re: Workup of carotid calcifications.

PMID- 9016250
TI  - Hemothorax due to spontaneous bleeding into posterior pararenal space.

PMID- 9016251
TI  - Sonography machines as a source of infection.

PMID- 9016252
TI  - Invasive thymoma presenting as pleural thickening.

PMID- 9016253
TI  - Pantopaque droplets: another cause of hyperintensity on unenhanced T1-weighted MR
      images of the brain.

PMID- 9016254
TI  - A simple method to avoid vertebral artery embolism during subclavian percutaneous
      transluminal angioplasty: provocative maneuver.

PMID- 9016255
TI  - Adjunct transjugular cholangiography for transjugular intrahepatic portosystemic
      shunt in chronic portal vein occlusion.

PMID- 9016256
TI  - Poststenotic aneurysm of the paraumbilical collateral vein: Doppler sonography
      findings.

PMID- 9016257
TI  - Gaping of the upper esophageal sphincter: a radiologic sign of swallowing
      dysfunction.

PMID- 9016258
TI  - Giant pulmonary hamartoma.

PMID- 9016259
TI  - What is PTSD?

PMID- 9016260
TI  - Images in neuroscience. Molecular Biology, IV. Identifying DNA transcription
      factors.

PMID- 9016261
TI  - The economic impact of psychotherapy: a review.
AB  - OBJECTIVE: The authors reviewed data involving the impact of providing
      psychotherapy for psychiatric disorders on costs of care. METHOD: In a search of
      the MEDLINE database limited to peer-reviewed papers published from 1984 through
      1994, 686 articles were identified. Forty-one articles, covering 35 studies, were
      found in which the intervention tested was psychotherapeutic and the study
      included measures of outcome that had some implications for cost. The exclusion
      criteria for reviewing these studies included absence of a comparison group, a
      focus on medical disorders instead of psychiatric illnesses, and outcomes that
      did not include cost data or measures from which costs could be inferred. On this
      basis, 18 of the 35 studies were selected for analysis. The studies were
      categorized according to whether or not subjects were randomly assigned to study
      groups. Two reviewers independently read each study to identify the following
      characteristics: inclusion criteria, exclusion criteria, types of interventions,
      main outcome variables, sample size, and statistical tests for significant
      differences between treatments. Outcomes had to include actual cost accounting or
      data on medical care utilization or work functioning. RESULTS: The findings of
      eight (80%) of the 10 clinical trials with random assignment and all eight (100%)
      of the studies without random assignment suggested that psychotherapy reduces
      total costs. CONCLUSIONS: Psychotherapy appears to have a beneficial impact on a
      variety of costs when used in the treatment of the most severe psychiatric
      disorders, including schizophrenia, bipolar affective disorder, and borderline
      personality disorder. Much of that impact accrues from reductions in inpatient
      treatment and decreases in work impairment.

PMID- 9016262
TI  - Modifiable neuronal connections: an overview for psychiatrists.
AB  - Synaptic plasticity is currently the target of much neurobiological research,
      because it is thought to play an important role in brain function (particularly
      memory formation). However, it has attracted little attention from psychiatrists
      to date despite accumulating evidence that links it to various clinical
      syndromes, including amnesia and possibly psychosis. The purpose of this article
      is to present an overview of the two major arms of synaptic plasticity research
      theoretical (the field of neural network modeling) and neurobiological (long-term
      potentiation). Artificial neural networks are a class of theoretical model that
      has been developed with the aim of understanding how information could, in
      principle, be represented by large numbers of interconnected and relatively
      simple units. Over the past few decades, several theoretical accounts of
      information-processing mechanisms have been developed, and these are briefly
      reviewed. The principle common to representation formation in nearly all neural
      networks is that of "associability"-the idea that streams of information are
      combined by forming, strengthening, or pruning connections between them to form
      new representations that can later be retrieved. Associability also lies at the
      heart of psychological theories of information storage in the brain. Research
      into associability has directed the attention of many experimenters toward the
      possible biological correlates of such mechanisms. Of particular interest is the
      recent discovery that some neurons appear to possess connections of modifiable
      strength. The implications of this finding for psychiatry are discussed in
      relation to representational disorders such as delusions and amnesia.

PMID- 9016263
TI  - Association of premorbid intellectual function with cerebral metabolism in
      Alzheimer's disease: implications for the cognitive reserve hypothesis.
AB  - OBJECTIVE: Clinical heterogeneity in Alzheimer's disease has been widely
      observed. One factor that may influence the expression of dementia in Alzheimer's
      disease is premorbid intellectual ability. It has been hypothesized that
      premorbid ability, as measured by educational experience, reflects a cognitive
      reserve that can affect the clinical expression of Alzheimer's disease. The
      authors investigated the relation between estimates of premorbid intellectual
      function and cerebral glucose metabolism in patients with Alzheimer's disease to
      test the effect of differing levels of premorbid ability on neurophysiological
      dysfunction. METHOD: In a resting state with eyes closed and ears occluded, 46
      patients with Alzheimer's disease were evaluated with positron emission
      tomography and [18F]-2-fluoro-2-deoxy-D-glucose to determine cerebral metabolism.
      Premorbid intellectual ability was assessed by a demographics-based IQ estimate
      and performance on a measure of word-reading ability. RESULTS: After the authors
      controlled for demographic characteristics and dementia severity, both estimates
      of premorbid intellectual ability were inversely correlated with cerebral
      metabolism in the prefrontal, pre-motor, and left superior parietal association
      regions. In addition, the performance-based estimate (i.e., reading ability) was
      inversely correlated with metabolism in the anterior cingulate, paracentral,
      right orbitofrontal, and left thalamic regions, after demographic and clinical
      variables were controlled for. CONCLUSIONS: The results suggest that higher
      levels of premorbid ability are associated with greater pathophysiological
      effects of Alzheimer's disease among patients of similar dementia severity
      levels. These findings provide support for a cognitive reserve that can alter the
      clinical expression of dementia and influence the neurophysiological
      heterogeneity observed in Alzheimer's disease.

PMID- 9016264
TI  - Consistency of memory for combat-related traumatic events in veterans of
      Operation Desert Storm.
AB  - OBJECTIVE: The nature of traumatic memories is currently the subject of intense
      scientific investigation. While some researchers have described traumatic memory
      as fixed and indelible, others have found it to be malleable and subject to
      substantial alteration. The current study is a prospective investigation of
      memory for serious combat-related traumatic events in veterans of Operation
      Desert Storm. METHOD: Fifty-nine National Guard reservists from two separate
      units completed a 19-item trauma questionnaire about their combat experiences 1
      month and 2 years after their return from the Gulf War. Responses were compared
      for consistency between the two time points and correlated with level of symptoms
      of posttraumatic stress disorder (PTSD). RESULTS: There were many instances of
      inconsistent recall for events that were objective and highly traumatic in
      nature. Eighty-eight percent of subjects changed their responses on at least one
      of the 19 items, while 61% changed two or more items. There was a significant
      positive correlation between score on the Mississippi Scale for Combat-Related
      Posttraumatic Stress Disorder at 2 years and the number of responses on the
      trauma questionnaire changed from no at 1 month to yes at 2 years. CONCLUSIONS:
      These findings do not support the position that traumatic memories are fixed or
      indelible. Further, the data suggest that as PTSD symptoms increase, so does
      amplification of memory for traumatic events. This study raises questions about
      the accuracy of recall for traumatic events, as well as about the well
      established but retrospectively determined relationship between level of exposure
      to trauma and degree of PTSD symptoms.

PMID- 9016265
TI  - Posttraumatic stress disorder associated with peacekeeping duty in Somalia for
      U.S. military personnel.
AB  - OBJECTIVE: The end of the Cold War has marked a period when the U.S. military is
      asked to secure peace under conditions in which peace is tenuous, yet the need
      for resolution of the conflict is great. Combat-trained soldiers are highly
      visible and are exposed to threats to their lives, yet are asked to exhibit
      restraint and neutrality. The psychiatric consequences of peace-keeping duty
      under these conflicting and volatile conditions have been underresearched. The
      authors examined the prevalence of posttraumatic stress disorder (PTSD)
      associated with exposure to peacekeeping duty in Somalia. METHOD: A large cohort
      of active duty personnel deployed to Somalia (N = 3,461) were surveyed
      approximately 5 months after their return to the United States. A variety of
      military service characteristics and exposure variables and PTSD symptoms were
      examined. RESULTS: Eight percent of peacekeepers were found to meet diagnostic
      criteria for PTSD. PTSD symptom severity was best predicted by the rewards of
      military service, war zone stress, and frustrations with peacekeeping (e.g.,
      restrictive rules of engagement). CONCLUSIONS: It is likely that the mission in
      Somalia represents a new paradigm of dangerous military operations for the United
      States. These data suggest that peacekeeping may be difficult to reconcile for
      some combat-trained soldiers and can create a risk for PTSD.

PMID- 9016266
TI  - Broader autism phenotype: evidence from a family history study of multiple
      incidence autism families.
AB  - OBJECTIVE: Studies of families ascertained through a single autistic proband
      suggest that the genetic liability for autism may be expressed in nonautistic
      relatives in a phenotype that is milder but qualitatively similar to the defining
      features of autism. The objective of this study was to examine behaviors that may
      define this broader phenotype in relatives ascertained through two autistic
      siblings. METHOD: The authors used a semistructured family history interview to
      compare the rates of social and communication deficits and stereotyped behaviors
      in relatives ascertained through two autistic siblings (families with multiple
      incidence autism; 25 families) with the rates in relatives of Down syndrome
      probands (30 families). RESULTS: Higher rates of social and communication
      deficits and stereotyped behaviors were found in the relatives in the families
      with multiple-incidence autism. CONCLUSIONS: These data suggest that further
      studies should be undertaken to delineate the boundaries of the broader autism
      phenotype and that this broader phenotype should be included in some future
      genetic analyses of this disorder.

PMID- 9016267
TI  - Resemblance of psychotic symptoms and syndromes in affected sibling pairs from
      the Irish Study of High-Density Schizophrenia Families: evidence for possible
      etiologic heterogeneity.
AB  - OBJECTIVE: The authors sought to determine whether the clinical manifestations of
      schizophrenia and other psychotic disorders are correlated in affected sibling
      pairs. METHOD: They examined, in 256 sibling pairs concordant for DSM-III-R
      schizophrenia and 457 sibling pairs concordant for all nonaffective psychoses
      ascertained in the Irish Study of High-Density Schizophrenia Families, similarity
      for 1) symptoms, course, and outcome; 2) symptom factors; and 3) syndromes,
      defined by latent class analysis. RESULTS: Global course and outcome, as well as
      all major symptoms except hallucinations, were modestly but significantly
      correlated in sibling pairs concordant for schizophrenia. Three symptom factors
      negative symptoms, positive symptoms, and affective symptoms-were all
      significantly correlated in concordant sib pairs. Latent class analysis suggested
      five schizophrenic syndromes. Class membership was significantly correlated in
      concordant sibling pairs. Similar results were found for sibling pairs concordant
      for nonaffective psychoses. CONCLUSIONS: The clinical manifestations of the
      schizophrenic syndrome (both narrowly and broadly defined) are moderately
      influenced by familial factors. From a familial/genetic perspective,
      schizophrenia as currently defined may be etiologically heterogeneous.

PMID- 9016268
TI  - Symptoms, subtype, and suicidality in patients with schizophrenia spectrum
      disorders.
AB  - OBJECTIVE: Suicide is the single largest cause of premature death among
      individuals with schizophrenia. This report examines the relationship between
      positive or negative symptoms, illness subtype, and suicidal behavior among
      patients with schizophrenia and schizophrenia spectrum disorders in a long-term
      follow-up cohort. METHOD: Based on index admission records, patients from the
      Chestnut Lodge Follow-Up Study with schizophrenia (N = 187), schizoaffective
      disorder (N = 87), schizophreniform disorder (N = 15), and schizotypal
      personality disorder (N = 33) were retrospectively assessed with the Positive and
      Negative Syndrome Scale, classical subtype criteria, and criteria for the deficit
      syndrome. Completed suicide, suicide attempts, and suicidal ideation during the
      follow-up period (average = 19 years) were ascertained by means of interviews
      with patients and/or surviving relatives. RESULTS: Over the follow-up period, 40%
      of the patients reported suicidal ideation, 23% reported suicide attempts, and
      6.4% died from suicide. Patients dead from suicide had significantly lower
      negative symptom severity at index admission than patients without suicidal
      behaviors. Two positive symptoms (suspiciousness and delusions), however, were
      more severe among successful suicides. The paranoid schizophrenia subtype was
      associated with an elevated risk (12%) and the deficit subtype was associated
      with a reduced risk (1.5%) of suicide. CONCLUSIONS: The impact of positive and
      negative symptoms on suicide risk has not been reported. These findings suggest
      that prominent negative symptoms, such as diminished drive, blunted affect, and
      social and emotional withdrawal, counter the emergence of suicidality in patients
      with schizophrenia spectrum disorders and that the deficit syndrome defines a
      group at relatively low risk for suicide. Prominent suspiciousness in the absence
      of negative symptoms defines a relatively high-risk group.

PMID- 9016269
TI  - Age-related differences in formal thought disorder in chronically hospitalized
      schizophrenic patients: a cross-sectional study across nine decades.
AB  - OBJECTIVE: This study used a cross-sectional design to examine the frequency of
      occurrence and severity of 10 different signs of thought disorder in
      schizophrenic patients across the lifespan. METHOD: Schizophrenic patients, who
      ranged in age from 19 to 96 years (N = 392), were examined with the Scale for
      Assessment of Thought, Language, and Communication. The cognitive functioning of
      the geriatric patients (patients over the age of 64, N = 120) was also assessed.
      RESULTS: Poverty of speech was more common and more severe in geriatric patients,
      while four different signs of thought disorder that reflect disconnected speech
      were less common and less severe in geriatric patients. Analysis of covariance
      found that the lower severity of disconnection thought disorders in the older
      patients was not attributable to differences in the amount of speech produced.
      CONCLUSIONS: Aspects of disconnected speech were less severe in older patients,
      while the severity and frequency of poverty of speech were greater. These
      findings suggest that the two previously identified separate dimensions of
      communication disorder in schizophrenia vary differently with age and possibly in
      their cognitive and biological underpinnings.

PMID- 9016270
TI  - Reduced G protein functions and immunoreactive levels in mononuclear leukocytes
      of patients with depression.
AB  - OBJECTIVE: Heterotrimeric G proteins play a pivotal role in postreceptor
      information transduction. These proteins were previously implicated in the
      biochemical mechanism underlying lithium action and in the pathophysiology of
      mood disorders. The present study sought to quantitatively and functionally
      evaluate G proteins in patients with major depression. METHOD: G proteins were
      measured in mononuclear leukocytes of 37 untreated patients with major depression
      and 31 comparison subjects. Receptor-coupled G protein function was evaluated
      through beta-adrenergic and muscarinic-agonist-induced increases in guanine
      nucleotide binding capacity, which were substantiated by quantitative measures of
      G proteins through immunoblot analyses that used polyclonal antibodies against
      stimulatory (Gs alpha) and inhibitory (Gi alpha) G proteins. RESULTS: Mononuclear
      leukocytes of depressed patients showed significantly reduced immunoreactive
      quantities of Gs alpha and Gi alpha together with markedly hypofunctional Gs and
      Gi. The reductions in both function and quantity of Gs and Gi were significantly
      correlated with the severity of depressive symptoms. Moreover, simultaneous
      quantitative and functional measurements in a large number of patients showed
      significant correlations between the function and the quantity of mononuclear
      leukocyte Gs and Gi proteins: CONCLUSIONS: These findings lend further support to
      the implication of G proteins in the pathophysiology of mood disorders. G protein
      functional and quantitative measurements in mononuclear leukocytes of patients
      with mood disorders may potentially serve as a biochemical marker for the
      affective state of these patients.

PMID- 9016271
TI  - High levels of Gs alpha in platelets of euthymic patients with bipolar affective
      disorder.
AB  - OBJECTIVE: Previous investigations have suggested the involvement of signal
      transducing guanine-nucleotide-binding proteins (G proteins) both in the
      mechanism of action of lithium and in the pathophysiology of bipolar affective
      disorder. To determine whether such G protein abnormalities are a trait
      phenomenon, the authors investigated the levels of G protein alpha subunits in
      platelets and lymphocytes of euthymic patients with bipolar affective disorder.
      METHOD: Selective antibodies were used to quantitate levels of G protein alpha
      subunits regulating adenylylcyclase activity (Gs alpha-both 45- and 52-kDa forms-
      and Gil-2 alpha) and those regulating phosphoinositide turnover (Gq/11 alpha) in
      both platelets and lymphocytes of 44 euthymic patients with bipolar affective
      disorder and 27 matched comparison subjects. RESULTS: Levels of both Gs alpha 45
      and Gs alpha 52 were higher in the platelets of the euthymic bipolar patients
      (both bipolar I and bipolar II) than in those of the comparison subjects.
      CONCLUSIONS: These findings are consistent with previous reports of high Gs alpha
      levels in bipolar affective disorder and, furthermore, suggest that such levels
      may be a trait abnormality for this condition.

PMID- 9016272
TI  - Inverse relationship of peripheral thyrotropin-stimulating hormone levels to
      brain activity in mood disorders.
AB  - OBJECTIVE: The author's goal was to investigate relationships between peripheral
      thyroid hormone levels and cerebral blood flow (CBF) and cerebral glucose
      metabolism in affectively ill patients. METHOD: Medication-free inpatients with
      major depression or bipolar disorder were studied with oxygen-15 water and
      positron emission tomography (PET) to measure CBF (N = 19) or with [18F]
      fluorodeoxyglucose and PET to measure cerebral glucose metabolism (N = 29).
      Linear regression was used to correlate global CBF and cerebral glucose
      metabolism with serum thyrotropin-stimulating hormone (TSH), triiodothyronine
      (T3), thyroxine (T4), and free T4 concentrations. Statistical parametric mapping
      was used to correlate regional CBF and cerebral glucose metabolism with these
      thyroid indexes. Post hoc t tests were used to further explore the relationships
      between serum TSH and global CBF and cerebral glucose metabolism. RESULTS: Serum
      TSH was inversely related to both global and regional CBF and cerebral glucose
      metabolism. These relationships persisted in the cerebral glucose metabolism
      analysis and, to a lesser extent, in the CBF analysis after severity of
      depression had been controlled for. In contrast, no significant relationships
      were observed between T3, T4, or free T4 and global or regional CBF and cerebral
      glucose metabolism. CONCLUSIONS: These data suggest that peripheral TSH
      (putatively the best marker of thyroid status) is inversely related to global and
      regional CBF and cerebral glucose metabolism. These findings indicate
      relationships between thyroid and cerebral activity that could provide
      mechanistic hypotheses for thyroid contributions to primary and secondary mood
      disorders and the psychotropic effects of thyroid axis manipulations.

PMID- 9016273
TI  - Stability of mood despite HIV illness progression in a group of homosexual men.
AB  - OBJECTIVE: The authors investigated the association between mood status and
      progression of HIV illness. METHOD: In a research clinic at a university medical
      center, 112 HIV-positive and 52 HIV-negative homosexual men were enrolled in a 4
      year prospective study with semi-annual assessments. The main study measures were
      psychiatric diagnoses according to the Structured Clinical Interview for DSM-III
      R; level of functioning and psychiatric symptoms according to the Global
      Assessment of Functioning Scale (axis V, DSM-III-R), the Hamilton depression and
      anxiety scales, the Brief Symptom Inventory, and the Beck Hopelessness Scale;
      stage of HIV illness; and CD4 cell count. RESULTS: Among the HIV-positive men,
      there was no increase in rates of syndromal depression and anxiety over the 4
      years despite substantial HIV illness progression. On all occasions, mean
      psychopathology symptom ratings were within the normal or not depressed range.
      However, compared to the HIV-negative men, the HIV-positive men had slightly more
      anxiety and somatic depressive symptoms throughout. The only measure that showed
      an increase in distress over time was orientation to the future; among the HIV
      positive men, hopes for the future waned across assessments. Attrition in the
      group was largely attributable to the loss of men with lower CD4 cell counts and
      more advanced HIV illness. However, study dropouts did not differ on any
      psychiatric measure from subjects who remained during the first 3 years.
      CONCLUSIONS: In this group no significant increase in syndromal or symptomatic
      depression or anxiety over nine semiannual assessments was found, despite
      substantial HIV illness progression and some deaths. Psychopathology did not
      predict dropout or death.

PMID- 9016274
TI  - Dopamine reuptake site densities in patients with social phobia.
AB  - OBJECTIVE: It has been suggested that social phobia is associated with
      dysfunction of the noradrenergic and dopaminergic systems, but there are no
      published anatomic data on the monoaminergic abnormalities found in the brains of
      phobic patients. The authors studied the density of dopamine reuptake sites in
      patients with social phobia. METHOD: The study included 11 patients with social
      phobia and 28 healthy comparison subjects, 11 of whom were age- and gender
      matched to the patients for the analyses. Measurement of the density of dopamine
      reuptake sites was performed by using a 123I-labeled cocaine analogue, [123I]beta
      CIT, with single photon emission computed tomography (SPECT). RESULTS: Blind
      quantitative analysis revealed that striatal dopamine reuptake site densities
      were markedly lower in the patients with social phobia than in the age- and
      gender-matched comparison subjects. CONCLUSIONS: The results indicate that social
      phobia may be associated with a dysfunction of the striatal dopaminergic system.

PMID- 9016275
TI  - Characteristics of 36 subjects reporting compulsive sexual behavior.
AB  - OBJECTIVE: The authors describe the sociodemographic features, phenomenology, and
      psychiatric comorbidity of 36 subjects reporting compulsive sexual behavior.
      METHOD: Twenty-eight men and eight women who responded to advertisements for
      "persons ... who have a problem with compulsive sexual behavior" completed
      structured and semistructured assessments, including the Diagnostic Interview
      Schedule for DSM-III-R disorders (axis I) and the Structured Interview for DSM
      III-R Personality Disorders, Revised (axis II). RESULTS: The typical subject was
      a 27-year-old man who reported experiencing compulsive sexual behavior for nearly
      9 years. Sexual behavior was described as excessive and poorly controlled and was
      associated with either subjective distress or impairment in interpersonal or
      occupational functioning or as overly time-consuming. Fourteen subjects (39%)
      reported a history of major depression or dysthymia, 15 (42%) a history of phobic
      disorder, and 23 (64%) a history of substance use disorder. Personality disorders
      were quite frequent, particularly the paranoid, histrionic, obsessive-compulsive,
      and passive-aggressive subtypes. The compulsive sexual behavior was quite varied
      and included both paraphilic (e.g., cross-dressing) and nonparaphilic (e.g.,
      compulsive masturbation) types. CONCLUSIONS: Compulsive sexual behavior may be a
      clinically useful concept, but it describes a heterogeneous group of individuals
      with substantial psychiatric comorbidity and diverse behavioral problems.

PMID- 9016276
TI  - Transitional objects and borderline personality disorder.
AB  - OBJECTIVE: The relationship of possession of transitional objects to the
      borderline personality disorder diagnosis was explored in a psychiatric inpatient
      setting. It was hypothesized that a greater proportion of inpatients who bring
      objects of special meaning with them to the hospital have borderline personality
      disorder. METHOD: Psychiatric inpatients (N = 146) were administered a
      semistructured interview to determine the presence of special (i.e.,
      transitional) objects in the hospital, at home, or during childhood. Borderline
      personality disorder was determined by criteria on a DSM-III-R borderline
      personality disorder checklist and by DSM-III-R discharge diagnosis. RESULTS:
      Significantly more patients who endorsed having transitional objects in the
      hospital or at home had the diagnosis of borderline personality disorder.
      Sensitivity, specificity, positive predictive power, and negative predictive
      power of the possession of the transitional object for the borderline personality
      disorder diagnosis were calculated. Specificity was higher than sensitivity, and
      negative predictive power was higher than positive predictive power in each
      instance. While these results suggest that absence of a transitional object is
      more likely to be associated with absence of borderline personality disorder than
      the presence of a transitional object is with the presence of borderline
      personality disorder, the sensitivity of a transitional object during adulthood
      to predict a diagnosis of borderline personality disorder was 63%, and the
      positive predictive power was 45%. CONCLUSIONS: A transitional object brought to
      the hospital may help remind the inpatient with borderline personality disorder
      of home or provide soothing during separation from home. The persistence of
      transitional objects into adulthood may inform the therapist of possible
      transference paradigms that may develop in treatment.

PMID- 9016277
TI  - Childhood-onset psychosis: evolution and comorbidity.

PMID- 9016279
TI  - Major depression following smoking cessation.
AB  - OBJECTIVE: The authors examined the incidence and predictors of major depression
      following successful smoking cessation treatment, with special attention to the
      influence of past major depression. METHOD: Three-month follow-up data were
      obtained from 126 subjects who successfully completed a 10-week smoking cessation
      program. RESULTS: The 3-month incidence of new major depression following
      treatment for nicotine dependence was 2%, 17%, and 30% among subjects with
      histories of no major depression, single major depression, and recurrent major
      depression, respectively. A history of major depression and persistent withdrawal
      symptoms independently predicted posttreatment major depression. CONCLUSIONS:
      Continued patient care beyond the 2-4-week period associated with the nicotine
      withdrawal syndrome is indicated when abstinence is attempted by smokers with
      prior major depression.

PMID- 9016280
TI  - Behavioral and neuroendocrine responses to sodium lactate infusion in subjects
      with posttraumatic stress disorder.
AB  - OBJECTIVE: Sodium lactate infusion has induced flashbacks accompanied by panic
      attacks in male combat veterans with posttraumatic stress disorder (PTSD) and
      concurrent panic disorder. This study addressed whether sodium lactate induces
      flashbacks or other intrusive PTSD symptoms in PTSD patients free of concurrent
      panic disorder. METHOD: Behavioral, cardiovascular, catecholamine, and cortisol
      responses to infusion of 0.5 M sodium lactate were compared among seven subjects
      with PTSD without panic disorder, seven subjects with panic disorder only, and
      seven healthy subjects. RESULTS: Six of the seven PTSD subjects but no panic
      disorder or healthy subjects reported flashbacks or other intrusive PTSD symptoms
      during lactate infusion. Flashbacks were accompanied by substantial anxiety
      symptoms. Cortisol levels were low in the PTSD subjects. CONCLUSIONS: Sodium
      lactate induces flashbacks in persons with PTSD without comorbid panic disorder.
      The relationship between anxiety responses accompanying a PTSD flashback and
      those in a panic attack remains unclear.

PMID- 9016281
TI  - Evidence of preference for a high-concentration sucrose solution in alcoholic
      men.
AB  - OBJECTIVE: The purpose of this study was to test in humans the finding from
      animal studies indicating an association between preference for more concentrated
      sweet solutions and excessive alcohol drinking. METHOD: The hedonic response to
      five different concentrations of sucrose solution was evaluated in 20 detoxified
      alcoholic and 37 nonalcoholic Caucasian men. All subjects repetitively tasted
      solutions with 0.05, 0.10, 0.21, 0.42, and 0.83 M sucrose concentrations and
      rated themselves on two scales measuring the intensity of sweetness and the
      likability of the solutions. RESULTS: A bimodal distribution of responses to the
      sweet solutions occurred in the nonalcoholic comparison group, with peaks at 0.05
      M and 0.42 M. In the alcoholic group, 65% of the subjects preferred the highest
      sucrose concentration (0.83 M), compared with only 16% of the nonalcoholic group.
      CONCLUSIONS: The results of this exploratory study support the hypothesis
      suggesting a positive association between the preference for stronger sweet
      solutions and alcohol dependence.

PMID- 9016282
TI  - Obsessive-compulsive disorder in patients with schizophrenia or schizoaffective
      disorder.
AB  - OBJECTIVE: The authors evaluated the frequency of DSM-III-R obsessive-compulsive
      disorder in patients with a primary diagnosis of schizophrenia or schizoaffective
      disorder. METHOD: Patients with schizophrenia (N = 52) or schizoaffective
      disorder (N = 25) were evaluated for the presence of obsessions and compulsions
      by means of the Structured Clinical Interview for DSM-III-R, the Yale-Brown
      Obsessive Compulsive Scale, chart review, and contact with the treating
      clinicians. RESULTS: Six (7.8%) of the 77 patients met the DSM-III-R criteria for
      both obsessive-compulsive disorder and schizophrenia or schizoaffective disorder.
      CONCLUSIONS: These findings suggest that obsessive-compulsive disorder occurs in
      a substantial percentage of patients with schizophrenia or schizoaffective
      disorder. The addition of medications targeted at obsessive-compulsive disorder
      may be beneficial to these patients but requires systematic evaluation.

PMID- 9016283
TI  - Obsessive-compulsive disorder with and without tics in an epidemiological sample
      of adolescents.
AB  - OBJECTIVE: This study was undertaken to discriminate subtypes of obsessive
      compulsive disorder in adolescents. METHOD: Forty individuals with obsessive
      compulsive spectrum disorders were ascertained from an epidemiological sample of
      861 adolescents. Interviews were conducted by child psychiatrists using
      semistructured diagnostic interviews, including a clinician-rated Yale-Brown
      Obsessive Compulsive Scale. Discriminant analysis was performed to compare the
      scores on the Yale-Brown scale of groups with and without comorbid tics and to
      compare boys and girls. RESULTS: Adolescents with tics were more prone to
      aggressive and sexual images and obsessions than were adolescents without tics;
      these differences could not be wholly attributed to sex differences. CONCLUSIONS:
      The subtypes among unreferred adolescents are similar to those of adult patients
      with obsessive-compulsive disorder with and without Gilles de la Tourette
      syndrome. Subtypes evident in adulthood may be established relatively early in
      the natural course of obsessive-compulsive disorder.

PMID- 9016284
TI  - Treatment of acute mania with gabapentin.

PMID- 9016285
TI  - Systematic desensitization as an alternative exposure strategy for PTSD.

PMID- 9016286
TI  - Nefazodone-induced hypoglycemia in a diabetic patient with major depression.

PMID- 9016287
TI  - Compulsive computer use.

PMID- 9016288
TI  - Risperidone overdose.

PMID- 9016289
TI  - Gaucher's disease initially diagnosed as depression.

PMID- 9016290
TI  - Propofol for sedation during rapid opiate detoxification.

PMID- 9016291
TI  - Gabapentin in the treatment of bipolar disorder.

PMID- 9016292
TI  - Nemonapride for the treatment of schizophrenia.

PMID- 9016293
TI  - Maternal infectious illness and schizophrenia.

PMID- 9016294
TI  - Hallucinatory changes.

PMID- 9016295
TI  - Assisted suicide for HIV patients.

PMID- 9016297
TI  - Traumatophilic diathesis, complemental series, and the original conceptual basis
      of PTSD.

PMID- 9016298
TI  - Cellular and molecular neuroscience of alcoholism.
AB  - Recent advances in neuroscience have made it possible to investigate the
      pathophysiology of alcoholism at a cellular and molecular level. Evidence
      indicates that ethanol affects hormone- and neurotransmitter-activated signal
      transduction, leading to short-term changes in regulation of cellular functions
      and long-term changes in gene expression. Such changes in the brain probably
      underlie many of the acute and chronic neurological events in alcoholism. In
      addition, genetic vulnerability also plays a role in alcoholism and, perhaps, in
      alcoholic medical disorders.

PMID- 9016299
TI  - Physiological properties of the normal lens.
AB  - The lens is an avascular organ suspended between the aqueous and vitreous humors
      of the eye. The cellular structure is symmetric about an axis passing through its
      anterior and posterior poles but asymmetric about a plane passing through its
      equator. Because of its asymmetric structure, the lens has historically been
      assumed to perform transport between the aqueous and vitreous humors. Indeed,
      when anterior and posterior surfaces were isolated in an Ussing chamber, a
      translens current was measured. However, in the eye, the two surfaces are not
      isolated. The vibrating probe technique showed the current densities at the
      surface of a free-standing lens were surprisingly large, about an order of
      magnitude greater than measured in an Ussing chamber, and were not directed
      across the lens. Rather, they were inward in the region of either anterior or
      posterior pole and outward at the equator. This circulating current is the most
      dramatic physiological property of a normal lens. We believe it is essential to
      maintain clarity; hence, this review focuses on factors likely to drive and
      direct it. We review properties and spatial distribution of lens Na+/K+ pumps,
      ion channels, and gap junctions. Based on these data, we propose a model in which
      the difference in electromotive potential of surface versus interior cell
      membranes drives the current, whereas the distribution of gap junctions directs
      the current in the observed pattern. Although this model is clearly too simple,
      it appears to quantitatively predict observed currents. However, the model also
      predicts fluid will move in the same pattern as ionic current. We therefore
      speculate that the physiological role of the current is to create an internal
      circulatory system for the avascular lens.

PMID- 9016300
TI  - Molecular physiology of vertebrate Na+/H+ exchangers.
AB  - This review describes recent progress concerning the molecular aspects of the
      Na+/H+ exchanger. The Na+/H+ exchanger is an important regulator for
      intracellular pH, cell volume, and transepithelial Na+ transport. It exists in
      virtually all cells with cell type-dependent pattern of isoform expression, and
      it is regulated in response to a variety of extracellular stimuli, among them not
      only agonists such as growth factors and hormones but also mechanical stimuli
      such as osmotic stress and cell spreading. Thus this transporter is also an
      excellent model to study the signal transduction. Since the first molecular
      cloning of the Na+/H+ exchanger, detailed studies revealed many interesting
      features of this transporter. At present, at least five different isoforms of the
      Na+/H+ exchanger are known. These isoforms differ in tissue localization,
      sensitivity of inhibitors, and mode of transcriptional and posttranscriptional
      regulation, allowing them to participate in different physiological processes. We
      have only started to understand an intriguing mechanism underlying these
      functional differences among the exchanger isoforms. Because the Na+/H+ exchanger
      is relatively simple in terms of its kinetic features, e.g., a simple 1:1
      stoichiometry of Na+ and H+ and no input of metabolic energy such as ATP
      hydrolysis, the study of its structural and mechanistic aspects would also serve
      as a good model to understand the general mechanism of various ion transporters.

PMID- 9016301
TI  - Neural control of renal function.
AB  - The renal nerves are the communication link between the central nervous system
      and the kidney. In response to multiple peripheral and central inputs, efferent
      renal sympathetic nerve activity is altered so as to convey information to the
      major structural and functional components of the kidney, the vessels, glomeruli,
      and tubules, each of which is innervated. At the level of each of these
      individual components, information transfer occurs via interaction of the
      neurotransmitter released at the sympathetic nerve terminal-neuroeffector
      junction with specific postjunctional receptors coupled to defined intracellular
      signaling and effector systems. In response to normal physiological stimuli,
      changes in efferent renal sympathetic nerve activity contribute importantly to
      homeostatic regulation of renal blood flow, glomerular filtration rate, renal
      tubular epithelial cell solute and water transport, and hormonal release.
      Afferent input from sensory receptors located in the kidney participates in this
      reflex control system via renorenal reflexes that enable total renal function to
      be self-regulated and balanced between the two kidneys. In pathophysiological
      conditions, abnormal regulation of efferent renal sympathetic nerve activity
      contributes significantly to the associated abnormalities of renal function
      which, in turn, are of importance in the pathogenesis of the disease.

PMID- 9016302
TI  - Developmental models of brain dysfunctions induced by targeted cellular ablations
      with methylazoxymethanol.
AB  - Abnormal brain development represents one of the major causes of neurological
      disorders in humans, and determining the factors responsible for generating
      specific brain malformations represents a formidable task for developmental
      neurobiology. The knowledge of the precise neurogenetic time table and the use of
      toxins, like methylazoxymethanol, able to interfere with neuroepithelial cells
      entering their last mitotic cycle, have allowed for targeted neuronal ablations
      in specific brain areas of the central nervous system (CNS) when administered at
      different gestational or postnatal days in various animal species. Of particular
      relevance are the studies in which ablations of neuronal populations of cortex,
      hippocampus, and cerebellum have been made. The results obtained show that these
      early ablations induce a number of neuroanatomic, neurochemical, and
      electrophysiological changes that give us the possibility to unravel the
      biochemical strategies utilized by surviving neurons to adapt to the perturbated
      environment. Most striking are the findings that target deprivation does not
      affect the survival of afferent neurons in the CNS (except for neurons of the
      lateral geniculate nucleus), in sharp contrast to the notion of target dependence
      for peripheral nervous system neurons. Animals showing selective ablations in the
      Ammon's horn of the hippocampus allow us to understand the complex biochemical
      pathways leading to changes in activity-dependent synaptic plasticity, and the
      data underscore the fundamental role of diverse Ca(2+)-dependent protein kinases,
      and their substrates, in modulating pre- and postsynaptic events during induction
      and maintenance of long-term potentiation (LTP). Because LTP represents a useful
      model to study molecular substrates of learning and memory, this animal model
      might be of relevance in understanding cognitive brain dysfunctions.

PMID- 9016303
TI  - Glutamate receptors in cortical plasticity: molecular and cellular biology.
AB  - Glutamate receptors (GluRs) provide the major excitatory input to cortical
      neurons. Four main subtypes of GluRs are distinguished, namely, N-methyl-D
      aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate, and
      metabotropic receptors. All of them have been implicated in neuronal plasticity,
      and this paper reviews data that may be pertinent to the role played by GluRs in
      neocortical plasticity both in adult animals as well as during postnatal
      development. Emphasis is given to receptor distribution analyzed by various
      means, such as physiological responses, ligand binding as revealed by receptor
      autoradiography, and expression of receptor subunits at both mRNA and protein
      (immunoreactivity) levels. Possible mechanisms of involvement of GluRs in plastic
      changes on cortical neuron response are reviewed, and data on up- and
      downregulation of GluRs in neocortical plasticity are summarized. Functional
      studies involving either activation or blocking, and effects of such manipulation
      on cortical plasticity are discussed.

PMID- 9016304
TI  - Regulation of intestinal sugar transport.
AB  - The recent surge in knowledge of cellular and molecular mechanisms of intestinal
      sugar transport has fueled an enormous interest in adaptive mechanisms regulating
      sugar transport. We first review several functional considerations that help us
      interpret the different patterns of adaptation for different nutrients. We then
      distinguish nonspecific adaptive mechanisms leading to parallel changes in
      transport of different nutrients from specific adaptive mechanisms only affecting
      the transport of a single nutrient. Nonspecific adaptive mechanisms include
      changes in mucosal surface area and in the ratio of transporting to
      nontransporting cells; specific mechanisms include changes in site density of
      transporters and in affinity constants. We also enumerate the patterns of
      regulation and describe how sugar transport is affected by changes in diet,
      energy budgets, and environmental salinity as well as by intestinal resection,
      starvation, stress, and age. We relate the various signals linking these stimuli
      to adaptive mechanisms and make predictions about the nature of these signals.
      Finally, we describe the significance of the interactions among sugar, fluid, and
      electrolyte transport mechanisms and of the paracellular pathway to
      transepithelial transport of sugars. We close by drawing attention to promising
      directions for future research.

PMID- 9016305
TI  - Quadruple immunofluorescence: a direct visualization method.
AB  - We describe fluorescence immunostaining of four different antigens in the same
      section. The fluorochrome conjugates used show highest emission in the blue,
      green, yellow, and red regions of the visible light spectrum, respectively.
      Specially designed single fluorochrome filter combinations allow selective
      visualization of each fluorochrome label in turn, without visible crosstalk with
      the others.

PMID- 9016306
TI  - Adrenomedullin receptor expression in human lung and in pulmonary tumors.
AB  - Adrenomedullin (AM) is a multifunctional regulatory peptide that stimulates
      cyclic AMP production in many target tissues and is highly expressed in the lung.
      Analysis of the distribution of the recently cloned AM receptor (AM-R) by non
      radioactive in situ hybridization revealed abundant expression in the basal cells
      of the airway epithelium and Type II pneumocytes. The expression of AM-R in the
      two cell types involved in epithelial regeneration of the lung suggests that AM
      may be relevant in such functions as organ development, wound repair, and
      epithelial turnover. AM-Rs are also synthesized in vivo and in vitro by a variety
      of tumor cells that also express the ligand, suggesting the existence of an
      autocrine loop that may be involved in tumor growth stimulation. The present
      findings suggest that the AM/AM-R regulatory system plays a major role in
      respiratory physiology and lung carcinogenesis and that new functions for AM
      remain to be identified.

PMID- 9016307
TI  - Differential effects of deuterium oxide on the fluorescence lifetimes and
      intensities of dyes with different modes of binding to DNA.
AB  - Deuterium oxide (D2O) increases both the fluorescence lifetime and the
      fluorescence intensity of the intercalating dyes propidium iodide (PI) and
      ethidium bromide (EB) when bound to nucleic acid structures. We have used
      spectroscopic analysis coupled with conventional and phase-sensitive flow
      cytometry to compare the alterations in intensity and lifetime of various DNA
      binding fluorochromes bound to DNA and Chinese hamster ovary (CHO) cells in the
      presence of D2O vs phosphate-buffered saline (PBS). Spectroscopic and flow
      cytometric studies showed a differential enhancement of intensity and lifetime
      based on the mode of fluorochrome-DNA interaction. The fluorescence properties of
      intercalating probes, such as 7-aminoactinomycin D (7.AAD) and ethidium homodimer
      II (EthD II) were enhanced to the greatest degree, followed by the probes TOTO
      and YOYO, and the non-intercalating probes Hoechst 33342 (HO) and 4,6-diamidino-2
      phenylindole (DAPI). The non-intercalating probe mithramycin (MI) gave unexpected
      results, showing a great enhancement of fluorescence intensity and lifetime in
      D2O, indicating that when staining is performed in PBS, much of the MI
      fluorescence is quenched by the solvent environment. Apoptotic subpopulations of
      HL-60 cells had a shorter lifetime compared to non-apoptotic subpopulations when
      stained with EthD II. These results indicate that accessibility of the dye
      molecules to the solvent environment once bound to DNA, leads to the differential
      enhancement effects of D2O on fluorescence intensity and lifetime of these
      probes.

PMID- 9016308
TI  - Biochemical properties and cytochemical localization of ouabain-insensitive,
      potassium-dependent p-nitrophenylphosphatase activity in rat atrial myocytes.
AB  - Enzyme activity that represents ouabain-insensitive, potassium-dependent p
      nitrophenylphosphatase (p-NPPase) was assessed in rat atrial myocytes by
      biochemical and cytochemical procedures. No activity was detected in parallel
      experiments with ventricular myocytes. Fixed tissues were incubated in a reaction
      medium containing Tricine buffer, p-nitrophenylphosphate (p-NPP), KCl, MgCl2,
      CaCl2, CeCl3. Triton X-100, levamisole, and ouabain. Final pH was adjusted to
      7.5. Biochemical studies showed that accumulation of p-nitrophenol in the medium
      was increased proportionally in accordance with the amount of incubated tissue.
      This activity was optimal with incubation at pH 7.5 and in the presence of KCl.
      Approximately 70% of the enzyme was inhibited by 2 mM CeCl3. Electron microscopic
      observations revealed reaction product (RP) at sites of ouabain-insensitive,
      potassium-dependent p-NPPase activity as electron-dense precipitate localized at
      the inner surface of the plasma membrane and at the T-tubules of atrial myocytes.
      Control experiments indicated that the activity was strongly inhibited by sodium
      orthovanadate and was repressed by omeprazole and 1,3-dicyclohexylcarbodiimide. X
      ray microanalysis confirmed the presence of cerium within the cytochemical RP.
      The ouabain-insensitive, K-dependent p-NPPase activity detected in the present
      study is considered to be an isoform of a P-type, H-transporting, K-dependent
      adenosine triphosphatase (H,K-ATPase).

PMID- 9016309
TI  - Upregulation of alpha 9 integrin and tenascin during epithelial regeneration
      after debridement in the cornea.
AB  - Stratified epithelia are exposed to abrasive forces and are required to respond
      rapidly to injury to minimize fluid loss and the risk for microbial infection.
      Healing involves a cell migratory phase to reestablish barrier function and cell
      proliferation to restratify the epithelium. Cell migration during re
      epithelialization involves cell sliding, termed sheet movement, during which
      cells retain their cell-cell junctions while dynamically altering their shape and
      cell-substrate interactions to permit movement across the exposed wound bed.
      Proteins of the integrin family of receptor molecules modulate cell shape, cell
      migration, and signal transduction in many cell types. In epithelial cells,
      integrins of the beta 1 family have been implicated in regulating cell
      proliferation and differentiation, alpha 9 beta b1 is one of the newer members of
      the integrin beta family and has been recently shown to function as a tenascin
      receptor. Although little is known about its function in vivo, studies in
      developing mouse cornea and eyelid suggest that it may play a role in epithelial
      differentiation. Using a debridement wound model in the mouse cornea, we show in
      this study that (a) in response to small debridement wounds that close without
      cell proliferation, alpha 9 integrin protein and mRNA are not induced during
      migration but are induced during restratification, (b) larger debridement wounds
      that require cell proliferation to generate the cells necessary for sheet
      movement result in a dramatic induction of alpha 9 protein and its mRNA during
      both migration and restratification, and (c) tenascin, an alpha 9 beta 1 ligand,
      accumulates beneath epithelial cells during restratification but not during cell
      migration. Therefore, alpha 9 integrin protein production and tenascin
      accumulation are dynamically regulated in response to corneal epithelial injury.

PMID- 9016310
TI  - Immunocytochemical phenotyping of disseminated tumor cells in bone marrow by uPA
      receptor and CK18: investigation of sensitivity and specificity of an
      immunogold/alkaline phosphatase double staining protocol.
AB  - Phenotyping of cytokeratin (CK)18-positive cells in bone marrow is gaining
      increasing importance for future prognostic screening of carcinoma patients.
      Urokinase-type plasminogen activator receptor (uPA-R) is one example of a
      potential aggressive marker for those cells. However, a valid and reliable double
      staining method is needed. Using monoclonal antibodies against uPA-R and CK18, we
      modified an immunogold/alkaline phosphatase double staining protocol. UPA-R/CK18
      positive tumor cell controls exhibited black uPA-R staining in 15-80% of cases
      and red CK18 staining in almost 100% of tumor cells. Isotype- and cross-matched
      controls were completely negative. Bone marrow from healthy donors was always
      CK18-negative. Reproducibility of CK18-positive cell detection was estimated in a
      series of specimens from 61 gastric cancer patients comparatively stained with
      the single alkaline phosphatase-anti-alkaline phosphatase (APAAP) and our double
      staining method (10(6) bone marrow cells/patient). In four cases, double staining
      could not reproduce CK18-positive cells. In 34 cases it revealed fewer or equal
      numbers, and in 23 cases more CK18-positive cells than the APAAP method. Overall
      quantitative analysis of detected cell numbers (838 in APAAP, range 1-280 in
      10(6); double staining 808, range 0-253) demonstrated relative reproducibility of
      APAAP results by double staining of 97%. Correlation of results between both
      methods was significant (p < 0.001, linear regression). Sensitivity of double
      staining tested in logarithmic tumor cell dilutions was one CK18-positive cell in
      300,000. Specific uPA-R staining was seen on CK18-positive cells in bone marrow
      from 29 of 61 patients, and also on single surrounding bone marrow cells. To test
      the specificity of this staining, bone marrow cytospins from 10 patients without
      tumor disease were stained for uPA-R with the APAAP method. uPA-R expression was
      confirmed in all 10 cases, with a mean of 6.5% uPA-R-positive cells in 1000 bone
      marrow cells (SEM 1.2%). These results suggest that our double staining protocol
      is a sensitive, reproducible, and specific method for routine uPA-R phenotyping
      of disseminated CK18-positive cells in bone marrow of carcinoma patients.

PMID- 9016311
TI  - Pathway and speed of calcium movement from blood to mineralizing enamel.
AB  - We studied by autoradiography the distribution of 45Ca in the enamel organ of
      frozen rats 4.3, 6.1, 7.8, 10.6 and 13.7 sec after an i.v. injection. The
      intercellular junctions of the proximal side of the smooth-ended ameloblast (SA)
      and the distal side of the ruffle-ended ameloblast (RA) were closed to calcium.
      The junctions of the distal side of SA, the proximal side of RA, and both sides
      of the secretory stage ameloblasts were not. The time required for calcium to
      pass through the ameloblast layer was less than 1.8 sec in the secretory stage
      and SA region. The time in the RA region was 3.5-6.3 sec. In the transitional
      region from RA to SA, a band of strong radioactivity appeared from the papillary
      layer of RA region towards the enamel of the SA region. The radioactivity in the
      secretory stage enamel increased almost linearly with time. The diffusion speed
      of calcium in the enamel was more than 50 microns for 1.8 sec in the maturation
      stage and less than 15 microns for 9.4 sec in the secretory stage. These results
      indicate that in the secretory and SA regions calcium moves to the enamel surface
      through the intercellular spaces of ameloblasts and in the RA region via RA
      cells.

PMID- 9016312
TI  - Immunocytochemical localization of heparin in secretory granules of rat
      peritoneal mast cells using a monoclonal anti-heparin antibody (ST-1).
AB  - We performed immunogold labeling with an ST-1 monoclonal antibody (IgM), specific
      for intact heparin, to define the subcellular localization of heparin in mast
      cells. Rat peritoneal mast cells were fixed by a modified Karnovsky method and
      embedded in Araldite. Ultrathin sections were first treated with sodium periodate
      and then sequentially incubated with MAb ST-1, rabbit anti-mouse IgM, and protein
      A-gold. By transmission electron microscopy, gold particles were localized inside
      cytoplasmic granules of peritoneal mast cells. In contrast, with the same
      procedure, no labeling was observed in mast cells from rat intestinal mucosa.
      Control sections of rat peritoneal or intestinal mucosa mast cells treated with
      an irrelevant MAb (IgM) did not show any labeling. Treatment with nitrous acid
      abolished the reactivity of MAb ST-1 with peritoneal mast cells. These results
      show that different mast cells can be identified regarding their heparin content
      by immunochemical procedures using MAb ST-1.

PMID- 9016313
TI  - Effects of shear stress on protein kinase C distribution in endothelial cells.
AB  - We studied the effects of shear stress on protein kinase C (PKC) in cultured
      human umbilical vein endothelial cells by use of a flow channel and a monoclonal
      antibody (MAb 1.3) that recognizes the PKC beta-isozyme. The fluorescence
      intensity (FI) of the secondary antibody, crystalline tetramethylrhodamine
      isothiocyanate, was determined by image analysis. The results on each of five
      shearing experiments were normalized by using the paired stationary control.
      After 30-min shearing at 2 N/m2, FI per cell increased to 1.6 times that of
      control, as did the mean FI per unit cell area. The FI per unit stained area and
      the stained area/cell area ratio were also increased significantly by shearing.
      The distribution of immunostaining in each cell was determined for its cortical,
      cytoplasmic, perinuclear, and nuclear regions. The normalized FI per unit area in
      all four regions and the stained area/cell area ratio in cortical and cytoplasmic
      regions were significantly higher in the sheared cells than in control; the
      increases were greatest in the cortical area. Double staining with rhodamine
      phalloidin and MAb 1.3 showed the association of actin with the PKC isozyme in
      both stationary and sheared cells.

PMID- 9016314
TI  - Detection of human topoisomerase II alpha in cell lines and tissues:
      characterization of five novel monoclonal antibodies.
AB  - We report five novel monoclonal antibodies (Ki-S1, Ki-S4, Ki-S6, Ki-S7, and Ki
      S8) reactive with a proliferation-related nuclear antigen. In immunoprecipitation
      and Western blot experiments using crude nuclear extracts, they recognized a
      protein of 170 kD that, after proteolytic digestion of the immunoprecipitate and
      sequencing of the resulting peptides, was identified as the alpha-isoform of
      human topoisomerase II. This was confirmed by testing the antibodies on a highly
      purified enzyme preparation. Crossreactivity with topoisomerase II beta was ruled
      out by testing the antibodies on crude extracts from yeast cells expressing the
      beta-isoform exclusively. The antibodies bind the antigen with different
      affinities and at different epitopes, apparently located within the carboxyl
      third of the enzyme. All five antibodies are suitable for archival material after
      adequate antigen retrieval, thereby enabling retrospective studies. This report
      illustrates the tissue and subcellular distribution of the antigen through the
      cell cycle by immunohistochemistry and confocal fluorescence microscopy. The
      antibodies will be useful tools in further analysis of morphological and
      functional aspects of topoisomerase II and may serve diagnostic purposes, as well
      as providing prognostic information in tumor pathology.

PMID- 9016315
TI  - Intracellular distribution of oligonucleotides delivered by cationic liposomes:
      light and electron microscopic study.
AB  - Synthesized oligonucleotides are used in anti-sense and anti-gene technology to
      control gene expression. Because cells do not easily take up oligonucleotides,
      cationic liposomes have been employed to facilitate their transport into cells.
      Although cationic liposomes have been used in this way for several years, the
      precise mechanisms of the delivery of oligonucleotides into cells are not known.
      Because no earlier reports have been published on the liposomal delivery of
      oligonucleotides at the ultrastructural level, we performed a study, using
      electron microscopy, on the cellular uptake and intracellular distribution of
      liposomal digoxigenin-labeled oligodeoxynucleotides (ODNs) at several
      concentrations (0.1, 0.2, an 1.0 microM) in CaSki cells. Two cationic lipids (10
      microM) were compared for transport efficiency: polycationic 2,3-dioleoyloxy-N
      [2(sperminecarboxamido)ethyl]-N,N-dimethyl -1-propanaminium trifluoroacetate
      (DOSPA) and monocationic dimethyl-dioctadecylammonium bromide (DDAB). Both
      liposomes contained dioleoyl-phosphatidylethanolamine (DOPE) as a helper lipid.
      Endocytosis was found to be the main pathway of cellular uptake of liposomal
      ODNs. After release from intracellular vesicles, ODNs were carried into the
      perinuclear area. The nuclear membrane was found to be a barrier against the
      penetration of ODNs delivered by liposomes into the nucleus. Release from
      vesicles and transport into the nuclear area was faster when the oligo-DDAB/DOPE
      complex had a positive net charge (0.1 and 0.2 microM ODN concentrations), and
      only under this condition were some ODNs found in nucleoplasm. Although
      DOSPA/DOPE could also efficiently deliver ODNs into the cytosol, no ODNs were
      found in nucleoplasm. These findings suggest that both the type of liposome and
      the charge of the oligo-liposome complex are important for determination of the
      intracellular distribution of ODNs.

PMID- 9016316
TI  - Recombinant galectin-1 recognizes mucin and epithelial cell surface glycocalyces
      of gastrointestinal tract.
AB  - Rat gastrointestinal (GI) tract is rich source of galectins, a family of
      mammalian galactoside-binding lectins. To determine which tissue component is the
      relevant glycoconjugate ligand for the galectins, we produced recombinant
      galectin-1 and surveyed its binding sites on tissue sections of rat GI tract.
      Mucin and epithelial surface glycocalyces of both gastric and intestinal mucosa
      were intensely stained. This finding raises the possibility that some GI tract
      galectins known to be secreted by the epithelia may recognize these
      glycoconjugates and crosslink them into a macromolecular mass. This galectin
      ligand complex may play a role in protecting the epithelial surface against
      luminal contents such as gastric acid, digestive enzymes, and foreign organisms.

PMID- 9016317
TI  - N- and O-linked oligosaccharides in the secretory granules of rat Paneth cells:
      an ultrastructural cytochemical study.
AB  - Paneth cells are located at the base of the intestinal glands. The origin,
      composition, and function of these cells have not been well established. The
      sharing of a common pathway of development with the goblet cells has been
      suggested. The aim of the present study was to explore the cytochemical
      composition of rat Paneth cells and to discuss a possible developmental
      relationship between goblet and Paneth cells. Lectins (WGA, LTA, UEA-1, AAA, and
      HPA) were used as a precise tool for the ultrastructural localization of
      carbohydrates. Several procedures were performed in combination with lectin
      cytochemistry: beta-elimination, a reaction that specifically removes O-linked
      oligosaccharides (typical of mucin-type glycoproteins of goblet cells); and
      treatment with peptide N-glycosidase F, an enzyme that removes N-linked
      oligosaccharides from glycoproteins. Secretory granules of Paneth cells showed a
      biphasic nature composed of an electron-lucent peripheral halo containing O
      linked oligosaccharides with GalNAc and GlcNAc residues and N-linked
      oligosaccharides with GlcNAc residues (only sparse Fuc residues were scarcely
      identified in O-linked oligosaccharides), and an electron-dense core containing N
      and O-linked oligosaccharides with Fuc residues. Neither GlcNAc nor GalNAc was
      identified. The occurrence of O-linked oligosaccharides in the Paneth cells and
      the biphasic nature of the secretory granules, similar to that of transitional
      cells intermediate between mucous and serous cells of other tissues, favor the
      hypothesis of a common lineage for goblet and Paneth cells.

PMID- 9016318
TI  - Nuclear scaffold proteins are differently sensitive to stabilizing treatment by
      heat or Cu++.
AB  - The distribution of three nuclear scaffold proteins (of which one is a component
      of a particular class of nuclear bodies) has been studied in intact K562 human
      erythroleukemia cells, isolated nuclei, and nuclear scaffolds. Nuclear scaffolds
      were obtained by extraction with the ionic detergent lithium diidosalicylate
      (LIS), using nuclei prepared in the absence of divalent cations (metal-depleted
      nuclei) and stabilized either by a brief heat exposure (20 min at 37C or 42C) or
      by Cu++ ions at 0C. Proteins were visualized by in situ immunocytochemistry and
      confocal microscopy. Only a 160-kD nuclear scaffold protein was unaffected by all
      the stabilization procedures performed on isolated nuclei. However, LIS
      extraction and scaffold preparation procedures markedly modified the distribution
      of the polypeptide seen in intact cells, unless stabilization had been performed
      by Cu++. In isolated nuclei, only Cu++ treatment preserved the original
      distribution of the two other antigens (M(r), 125 and 126 kD), whereas in heat
      stabilized nuclei we detected dramatic changes. In nuclear scaffolds reacted with
      antibodies to 125 and 126-kD proteins, the fluorescent pattern was always
      disarranged regardless of the stabilization procedure. These results, obtained
      with nuclei prepared in the absence of Mg+2 ions, indicate that heat treatment
      per se can induce changes in the distribution of nuclear proteins, at variance
      with previous suggestions. Nevertheless, each of the proteins we have studied
      behaves in a different way, possibly because of its specific association with the
      nuclear scaffold.

PMID- 9016319
TI  - Embedding of bone samples in methylmethacrylate: an improved method suitable for
      bone histomorphometry, histochemistry, and immunohistochemistry.
AB  - Methylmethacrylate (MMA) embedding of undecalcified bone biopsies is a technique
      widely used for bone histomorphometry. However, conventional MMA embedding causes
      almost complete loss of enzyme activity and protein antigenicity in the tissues.
      Recently, an MMA embedding technique has been reported that preserves enzyme
      activity and antigenic determinants in bone tissue. We describe here a
      modification of this embedding method. For our modified MMA embedding process,
      commercially available methacrylates can be used without purification, and the
      histologic quality of bone sections is comparable to that of conventionally MMA
      embedded bone specimens. The technique reported here can be employed for
      embedding of larger bone samples and is suitable for histochemical and
      immunohistological applications as well as for routine bone histomorphometry. By
      addition of methylbenzoate during infiltration and polymerization of the plastic,
      the antigenicity of the tissue was improved. As applications of this novel
      technique, demonstration of alkaline phosphatase and tartrate-resistant acid
      phosphatase as well as positive labeling of Kupffer cells and osteoclasts with
      the monoclonal antibody ED1 in sections of liver, tibiae, and vertebrae of 3
      month-old rats was demonstrated. The method described here might be useful for
      the inclusion of histochemical and immunohistological methods into bone
      histomorphometry.

PMID- 9016320
TI  - Fluorescein-labeled tyramide strongly enhances the detection of low
      bromodeoxyuridine incorporation levels.
AB  - Immunocytochemical detection of bromodeoxyuridine (BrdU) labeling can be hampered
      by low BrdU incorporation levels. We describe here an amplification method for
      weak BrdU immunosignals. The tyramide signal amplification method based on
      catalyzed reporter deposition (CARD) uses fluorescein-labeled tyramide as a
      substrate for horseradish peroxidase. The enzyme catalyzes the formation of
      highly reactive tyramide radicals with a very short half-life, resulting in the
      binding of fluorescein-conjugated tyramide only at the site of the enzymatic
      reaction. MCF-7 cells were grown in vitro in medium containing charcoal-stripped
      fetal bovine serum supplemented by growth factors. Under these culture
      conditions, the BrdU immunosignal was hard to detect but could be enhanced
      specifically by the tyramide signal amplification system, resulting in clear-cut
      differences between BrdU-negative and BrdU-positive cells. This enabled rapid and
      objective quantification of the BrdU labeling index without the risk of
      underestimating the number of cells in S-phase. Therefore, this amplification of
      BrdU immunosignals might also prove valuable for in vivo cancer prognosis, cell
      kinetics studies, and computer-assisted image analyses.

PMID- 9016321
TI  - 2-Phenyl-4(5)-[[4-(pyrimidin-2-yl)piperazin-1-yl]methyl]imidazole. A highly
      selective antagonist at cloned human D4 receptors.

PMID- 9016322
TI  - Rationally designed inhibitors of inosine monophosphate dehydrogenase.
AB  - Functionalized 2-alkyl derivatives of inosinic acid have been synthesized to
      serve as reversible as well as irreversible inhibitors of the human type II
      enzyme inosine monophosphate dehydrogenase. These compounds were designed to
      react with Cys-331 of the enzyme to form covalent bonds so as to interfere with
      the normal enzyme mechanism which involves attack of Cys-331 at C-2 of the
      substrate. Mass spectrometric analysis of the reaction products after enzymatic
      degradation confirmed the appropriateness of the inhibitor design.

PMID- 9016323
TI  - Synthesis and characterization of technetium-99m-labeled tropanes as dopamine
      transporter-imaging agents.
AB  - In the development of novel Tc-99m-labeled tropane derivatives as dopamine
      transporter (reuptake site)-imaging agents, a series of neutral and lipophilic
      complexes containing bis-(aminoethanethiol) as a neutral complexing moiety for a
      [99mTc]TcO3+ center core was successfully prepared. Biological evaluation of the
      Tc-99m-labeled complexes 13-16 as central nervous system (CNS) dopamine
      transporter-imaging agents was reported. Synthesis of the tropane derivatives was
      achieved by stepwise reactions adding two aminoethanethiol units. The final free
      thiol ligands were obtained by deblocking the 4-methoxybenzyl protecting group
      with Hg(OAc)2 to obtain trifluoroacetate salts. All of the Tc-99m complexes, with
      the exception of 16, displayed good initial brain uptake and selective uptake in
      the striatal area, where dopamine transporters are concentrated. One of the
      compounds, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1]oct-2
      yl]methyl](2-mercaptoethyl)amino]ethy] amino]ethanethiolato-(3-)-N2,N2',S2,S2']
      oxo-[1R-(exo-exo)]- [99mTc]technetium,[99mTc]TRODAT-1 (13), displayed the highest
      initial uptake in rat brain (0.4% at 2 min post iv injection); the
      striatal/cerebellar (ST/ CB) ratio reached 2.8 at 60 min after an iv injection.
      The specific uptake in rat brain can be blocked by pretreating rats with a
      competing dopamine transporter binding agent, beta-CIT (RTI-55, 2 beta
      carbomethoxy-3 beta-(4-iodophenyl)tropane; iv, 1 mg/kg), which reduced the
      regional brain uptake ratio (ST/CB) to 1.2. In contrast, the specific striatal
      uptake was not affected by pretreating rats with a noncompeting ligand, haldol
      (iv, 1 mg/kg). After an iv injection of 9 mCi of [99mTc]TRODAT-1 (13), in vivo
      images of baboon brain using single-photon emission-computed tomography exhibited
      excellent localization in striatum (basal ganglia), where dopamine neurons are
      known to be concentrated. This series of compounds may provide a convenient
      source of short-lived imaging agents for routine diagnosis of CNS diseases (i.e.,
      Parkinson's disease) in which changes in the dopamine transporter concentration
      are implicated.

PMID- 9016324
TI  - Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic
      agonists.
AB  - A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at
      alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have
      potent and selective agonist activity at the alpha 2-adrenoceptors. The most
      potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole,
      proved efficacious for the reduction of intraocular pressure upon topical
      administration and for the reduction of blood pressure upon intravenous
      administration. During the course of our studies, we developed a new reagent that
      allowed rapid assembly of the target compounds. This reagent, N-(2,2
      diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low
      temperature storage conditions.

PMID- 9016325
TI  - Cardioselective antiischemic ATP-sensitive potassium channel (KATP) openers. 5.
      Identification of 4-(N-aryl)-substituted benzopyran derivatives with high
      selectivity.
AB  - This paper describes our studies aimed at the discovery of structurally distinct
      analogs of the cardioprotective KATP opener BMS-180448 (2) with improved
      selectivity for the ischemic myocardium. The starting compound 6, derived from
      the indole analog 4. showed good cardioprotective potency and excellent
      selectivity compared to 2 and the first-generation KATP opener cromakalim (1).
      The structure-activity studies indicate that increasing the size of the alkyl
      ester leads to diminished potency as does its replacement with a variety of other
      groups (nitrile, methyl sulfone). Replacement of the ethyl ester of 6 with an
      imidazole gave the best compound 3 (BMS-191095) of this series which maintains
      the potency and selectivity of its predecessor 6. The results described in this
      publication further support that there is no correlation between vasorelaxant and
      cardioprotective potencies of KATP openers. Compound 3 is over 20- and 4000-fold
      more selective for the ischemic myocardium than 2 and cromakalim (1),
      respectively. The selectivity for the ischemic myocardium is achieved by
      reduction of vasorelaxant potency rather than enhancement in antiischemic
      potency. As for cromakalim (1) and 2, the cardioprotective effects of compound 3
      are inhibited by cotreatment with the KATP blocker glyburide, indicating that the
      KATP opening is involved in its mechanism of cardioprotection. With its good oral
      bioavailability (47%) and plasma elimination half-life (3 h) in rats, compound 3
      offers an excellent candidate to investigate the role of residual vasorelaxant
      potency of 2 toward its cardioprotective activity in vivo.

PMID- 9016326
TI  - Highly selective, novel analogs of 4-[2-(diphenylmethoxy)ethyl]- 1
      benzylpiperidine for the dopamine transporter: effect of different aromatic
      substitutions on their affinity and selectivity.
AB  - Several analogs of the potent and selective dopamine transporter (DAT) ligand 4
      [2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, 1a, were prepared and biologically
      evaluated at the dopamine and serotonin transporter (SERT) sites. Several
      substituents were introduced in the aromatic rings to evaluate the influences of
      electronic and steric interactions in their binding to the DAT. All the novel
      analogs showed preferential interaction at the DAT compared with the SERT.
      Different aromatic substitutions in the phenyl ring of the N-benzyl part of the
      molecule played a key role in the selectivity. In general, compounds with strong
      electron-withdrawing substituents were most active and selective at the DAT.
      Thus, compounds 5a (R = F) and 11b (R = NO2) were among the most potent (IC50 =
      17.2 and 16.4 nM, respectively) and most selective (SERT/DAT = 112 and 108,
      respectively) and were far more selective than GBR 12909 (SERT/DAT = 6).
      Bioisosteric replacement of one of the phenyl rings of the diphenylmethoxy moiety
      by a thiophene ring was tolerated well and produced the most potent compound 13b
      (IC50 = 13.8 nM) in the series. Our current structure-activity studies of these
      piperidine analogs resulted in the generation of second generation of GBR-type
      compounds, and all of these new compounds reported here were more selective than
      GBR 12909 in interacting with the DAT over the SERT.

PMID- 9016328
TI  - Discovery of potent isoxazoline glycoprotein IIb/IIIa receptor antagonists.
AB  - Using the isoxazoline as a common structural feature, three series of
      glycoprotein IIb/IIIa receptor antagonists were evaluated, culminating in the
      discovery of XR299 (30). In an in vitro assay of platelet inhibition, XR299 had
      an IC50 of 0.24 microM and was a potent antiplatelet agent when dosed
      intravenously in a canine model. It was shown through X-ray studies of the
      cinchonidine salt 49 that the receptor required the 5(R)-stereochemistry for high
      potency. The ethyl ester prodrug of XR299, XR300 (29), was orally active in the
      dog.

PMID- 9016327
TI  - Synthesis and anticonvulsant activities of 3,3-dialkyl- and 3-alkyl-3-benzyl-2
      piperidinones (delta-valerolactams) and hexahydro-2H-azepin-2-ones (epsilon
      caprolactams).
AB  - A series of 3-substituted 2-piperidinone (delta-valerolactam) and hexahydro-2H
      azepin-2-one (epsilon-caprolactam) derivatives were prepared and evaluated as
      anticonvulsants in mice. In the 2-piperidinone series, 3,3-diethyl compound 7b is
      the most effective anticonvulsant against pentylenetetrazole-induced seizures
      (ED50, 37 mg/kg; PI (TD50/ED50), 4.46), and 3-benzyl compound 4c (ED50, 41 mg/kg;
      PI, 7.05) is the most effective anticonvulsant against seizures induced by
      maximal electroshock. By contrast, none of the epsilon-caprolactams tested had
      anticonvulsant effects below doses causing rotorod toxicity. log P values were
      correlated with neurotoxicity and [35S]TBPS displacement, but not with
      anticonvulsant activity. Electrophysiological evaluations of selected compounds
      from each series indicated that both the delta-valero-lactams and epsilon
      caprolactams potentiated GABA-mediated chloride currents in rat hippocampal
      neurons.

PMID- 9016329
TI  - Synthesis and in vitro activity of 3 beta-substituted-3 alpha-hydroxypregnan-20
      ones: allosteric modulators of the GABAA receptor.
AB  - Two naturally occurring metabolites of progesterone, 3 alpha-hydroxy-5 alpha- and
      5 beta-pregnan-20-one (1 and 2), are potent allosteric modulators of the GABAA
      receptor. Their therapeutic potential as anxiolytics, anticonvulsants, and
      sedative/hypnotics is limited by rapid metabolism. To avoid these shortcomings, a
      series of 3 beta-substituted derivatives of 1 and 2 was prepared. Small
      lipophilic groups generally maintain potency in both the 5 alpha- and 5 beta
      series as determined by inhibition of [35S]TBPS binding. In the 5 alpha-series, 3
      beta-ethyl, -propyl, -trifluoromethyl and -(benzyloxy)methyl, as well as
      substituents of the form 3 beta-XCH2, where X is Cl, Br, or I or contains
      unsaturation, show limited efficacy in inhibiting [35S]TBPS binding. In the 5
      beta-series, the unsubstituted parent 2 is a two-component inhibitor, whereas all
      of the 3 beta-substituted derivatives of 2 inhibit TBPS via a single class of
      binding sites. In addition, all of the 3-substituted 5 beta-sterols tested are
      full inhibitors of [35S]TBPS binding. Electrophysiological measurements using
      alpha 1 beta 2 gamma 2L receptors expressed in oocytes show that 3 beta-methyl-
      and 3 beta-(azidomethyl)-3 alpha-hydroxy-5 alpha-pregnan-20-one (6 and 22,
      respectively) are potent full efficacy modulators and that 3 alpha-hydroxy-3 beta
      (trifluoromethyl)-5 alpha-pregnan -20-one (24) is a low-efficacy modulator,
      confirming the results obtained from [35S]TBPS binding. These results indicate
      that modification of the 3 beta-position in 1 and 2 maintains activity at the
      neuroactive steroid site on the GABAA receptor. In animal studies, compound 6
      (CCD 1042) is an orally active anticonvulsant, while the naturally occurring
      progesterone metabolites 1 and 2 are inactive when administered orally,
      suggesting that 3 beta-substitution slows metabolism of the 3-hydroxyl, resulting
      in orally bioavailable steroid modulators of the GABAA receptor.

PMID- 9016330
TI  - 3 alpha-Hydroxy-3 beta-(phenylethynyl)-5 beta-pregnan-20-ones: synthesis and
      pharmacological activity of neuroactive steroids with high affinity for GABAA
      receptors.
AB  - Neuroactive steroids that allosterically modulate GABAA receptors have potential
      uses as anticonvulsants, anxiolytics, and sedative-hypnotic agents. Recently, a
      series of pregnanes substituted with simple alkyl groups at the 3 beta-position
      were synthesized and found to be active in vitro. The present report describes
      the synthesis of a series of substituted 3 alpha-hydroxy-3 beta
      (phenylethynyl)pregnan-20-ones and their in vitro structure-activity relationship
      determined by their potency for inhibition of [35S]TBPS binding in rat brain
      membranes. Appropriate substitution of the phenyl group results in ligands with
      particularly high affinity for the neuroactive steroid site on GABAA receptors
      (e.g., 4-acetyl 28, IC50 10 nM). The potency of selected steroids was confirmed
      electrophysiologically in oocytes expressing cloned human GABAA alpha 1 beta 2
      gamma 2L receptors (e.g., compound 28, EC50 6.6 nM). Consistent with their in
      vitro activity, some of the 3 beta-(phenylethynyl)-substituted steroids displayed
      anticonvulsant activity in the pentylenetetrazol (PTZ) and maximal electroshock
      (MES) tests following ip administration in mice. Notably, the 3 beta-[(4
      acetylphenyl)ethynyl]-19-nor derivative 36 demonstrated an attractive
      anticonvulsant profile (PTZ and MES ED50 values of 2.8 and 9.2 mg/kg,
      respectively). A new pharmacophore for the neuroactive steroid site of GABAA
      receptors is proposed based upon the high affinity of certain substituted 3 beta
      (phenylethynyl) steroids.

PMID- 9016331
TI  - Synthesis and evaluation of trimetoquinol derivatives: novel thromboxane
      A2/prostaglandin H2 antagonists with diminished beta-adrenergic agonist activity.
AB  - Trimetoquinol (TMQ, 1) is a unique catecholamine with a strong stereodependence
      for agonism at beta-adrenergic (S > > R) and antagonism at thromboxane
      A2/prostaglandin H2 (TP; R > > S) receptors. Our laboratory has reported the
      effects of N-alkylation and modification of the trisubstituted benzyl group in
      these receptor systems. For iodinated derivative 5, maintaining potency in TP
      receptor systems (112%) was coupled with maintaining limited potency in beta
      adrenergic receptor systems (34% for beta 1 and 47% for beta 2). In this study,
      several diverse TMQ derivatives were prepared to probe for binding interactions
      specific to a particular receptor system. Planar amidine 2, which was designed to
      explore the importance of TMQ's chiral center, showed a dramatic loss of potency
      (< 1%) in each receptor system. Likewise, the homologation of a previously
      described N-benzyl derivative (3) to the N-phenylethyl derivative 4 also showed
      reduced potency (< 3%) in both receptor systems. However, modification of the
      trimethoxybenzyl group of TMQ to a 4-hydroxy-3-nitrobenzyl group (7) provided a
      unique lead for TMQ derivatives with significant potency in TP receptor systems
      (91%) and reduced potency in beta-adrenergic receptor systems (4% for beta 1 and
      19% for beta 2).

PMID- 9016332
TI  - Threonine6-bradykinin: structural characterization in the presence of micelles by
      nuclear magnetic resonance and distance geometry.
AB  - The conformation of the natural peptide [Thr6]-bradykinin, Arg1-Pro2-Pro3-Gly4
      Phe5-Thr6-Pro7-Phe8-Arg9, is investigated by NMR spectroscopy and computer
      simulations in an aqueous solution of sodium dodecyl sulfate micelles. The
      structural analysis of the peptide is of particular interest since it displays a
      different biological profile from bradykinin despite the high sequence homology
      (only one conservative substitution: Ser6/Thr6) and the fact that both peptides
      bind and activate common receptors. The SDS micelles provide a model system for
      the membrane-interface environment the peptide experiences when interacting with
      the membrane-embedded receptor and allow for the conformational examination of
      the peptide using high-resolution NMR techniques. The NMR spectra show that the
      micellar system induces a secondary structure in the otherwise inherently
      flexible peptide (as observed in benign aqueous solution). The distance geometry
      calculations indicate a beta-turn of type I about residues 7-8 as the preferred
      conformation. The results of ensemble calculations reveal conformational changes
      occurring rapidly on the NMR time scale and allow for the identification of three
      different families of conformations that average to reproduce the NMR
      observables. The three families differ in the type of conformation adopted at the
      C-terminus: type I beta-turn, type II beta-turn and a third conformation,
      intermediate between the two beta-turns. The structural results support the
      hypothesis of the determining role of the C-terminal conformation for biological
      activity and can provide an explanation of the different activities observed for
      bradykinin and [Thr6]-bradykinin.

PMID- 9016333
TI  - Threonine6-bradykinin: molecular dynamics simulations in a biphasic membrane
      mimetic.
AB  - The natural peptide [Thr6]-bradykinin, Arg1-Pro2-Pro3-Gly4-Phe5-Thr6-Pro7-Phe8
      Arg9, has been conformationally examined by molecular dynamics simulations using
      a two-phase box consisting of H2O and CCl4 to mimic the micellar environment
      utilized in the 1H-NMR studies. The different conformations generated from
      distance geometry calculations were refined with extensive molecular dynamics
      simulations. The resulting conformations provide additional structural insight
      into the differing biological activities of native bradykinin and [Thr6]
      bradykinin, produced by the one conservative substitution Thr6 for Ser6. In
      addition, the simulations give some indication of the interaction of the peptide
      with the biphasic, hydrophilic/hydrophobic environment of the micelle. Such
      information is vital given the accumulating data indicating that the peptide
      first interacts with the membrane before the membrane-bound receptor. The
      structures of membrane-bound [Thr6]-bradykinin developed here provide
      experimental support for the interaction of residues 7 and 8 with the core of the
      membrane-bound receptor and the N-terminus and C-terminal arginine interacting
      with the extracellular portion of the receptor.

PMID- 9016334
TI  - Antirheumatic agents: novel methotrexate derivatives bearing a benzoxazine or
      benzothiazine moiety.
AB  - Novel methotrexate (MTX) derivatives bearing dihydro-2H-1,4-benzothiazine or
      dihydro-2H-1,4-benzoxazine were synthesized and tested for in vitro
      antiproliferative activities against human synovial cells (hSC) and human
      peripheral blood mononuclear cells (hPBMC) obtained from patients with rheumatoid
      arthritis and healthy volunteers, respectively. In vivo antiarthritic activities
      of these derivatives were also evaluated in a rat adjuvant arthritis model. N-[[4
      [(2,4-Diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7
      yl]carbonyl]-L-glutamic acid (3c) exhibited more potent antiproliferative
      activities in hSC and hPBMC than MTX in vitro. Antiproliferative activities of N
      [[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzoxazin-7
      yl]carbonyl]-L-homoglutamic acid (3b) and N-[[4-[(2,4-diaminopteridin-6
      yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-homoglutamic acid
      (3d) (MX-68) were comparable to that of MTX in these in vitro assays. Compounds
      3b,d (MX-68) significantly suppressed progression of the adjuvant arthritis in a
      dose-dependent manner ranging from 0.5 to 2.5 mg/kg (po). In addition, 3d (MX-68)
      completely suppressed this progression at the dose of 2.5 mg/kg (po).
      Importantly, 3d (MX-68) having benzothiazine and homoglutamate, as expected, did
      not undergo polyglutamation, a process which may be responsible for the
      associated side effects of MTX. These results suggest that 3d (MX-68) is a potent
      and safe candidate antirheumatic agent, absent of the side effects of MTX.

PMID- 9016335
TI  - Chemical and biological studies on a series of novel (trans-(1R,2R)-, trans
      (1S,2S)-, and cis-1,2-diaminocyclohexane)platinum(IV) carboxylate complexes.
AB  - A series of novel platinum(IV) complexes of the type DACH-PtIV-trans-(Y)2-cis-X
      (where DACH = trans-(1R,2R)-, trans-(1S,2S)-, or cis-1,2-diaminocyclohexane; X =
      diacetate, oxalate, malonate, methylmalonate, cyclobutanecarboxylate (CBCA), or
      1,1-cyclobutanedicarboxylate (CB-DCA); and Y = acetate or trifluoroacetate) has
      been synthesized and characterized by elemental analysis, IR, and 195Pt-NMR
      spectroscopy. The compounds have been tested against cisplatin-sensitive L1210/0
      leukemia, cisplatin-resistant L1210/DDP leukemia, and M5076 reticulosarcoma cell
      lines in vivo. Most of these analogs displayed reasonable activity against
      L1210/0 cells (%T/C = 135 to > 700). There were no gross differences in activity
      between analogs containing isomers of DACH. Selected compounds were evaluated
      against L1210/DDP tumor models in which they demonstrated reduced but significant
      activity compared with activity in the L1210/0 model. Interestingly, complex 20,
      PtIV(trans-1R,2R-DACH)-trans-(acetate)2-methylmalonate, was highly active against
      M5076, although it had no activity against the L1210 lines. The results
      demonstrate that specific combinations of axial and equatorial carboxylate
      ligands, together with the DACH carrier ligand, can favorably modulate the
      antitumor properties of platinum complexes and enhance circumvention of cisplatin
      resistance.

PMID- 9016336
TI  - Stereoselective synthesis and biodistribution of potent [11C]-labeled antagonists
      for positron emission tomography imaging of muscarinic receptors in the airways.
AB  - Quantitation of muscarinic receptors in the lungs in vivo with positron emission
      tomography (PET) is of clinical interest. For that purpose we decided to develop
      [11C]-labeled ligands with a high affinity (KD < 0.1 nM). Three quaternary
      muscarinic antagonists, racemic N-methylpiperidin-4-yl 2-cyclohexyl-2-hydroxy-2
      phenylacetate methiodide 1a (pKB = 10.39), its (R)-isomer 1b (pKB = 11.08), and
      (R,R)-quinuclidin-3-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide 2 (pKB =
      11.28), were labeled by reacting [11C]CH3I with their tertiary amine precursors.
      The enantiomerically pure tertiary amine precursors were prepared by
      stereoselective synthesis starting from (R)-(-)-mandelic acid. In vitro binding
      assay of 1b and 2 demonstrated that both ligands bind with very high affinity to
      the muscarinic receptor subtypes M1, M2, and M3. They are more potent than the
      muscarinic antagonist (R)-N-methylquinuclidinyl benzilate ((R)-MQNB).
      Distribution studies with 1a, 1b, and 2 in control and atropine-treated male
      Wistar rats demonstrated significant specific binding (90-99% of total issue
      uptake) in tissues containing cholinoceptors (heart, intestine, lung, pancreas,
      spleen, stomach, submandibular gland). Because the tissue/plasma concentration
      ratios of 1b are most favorable, this ligand was used for further evaluation.
      Analysis of plasma samples showed a very rapid clearance (t1/2 = 0.3 min) of the
      radioligand 1b and a relatively slow appearance of a hydrophilic metabolite. At
      15 min postinjection of 1b, analysis of heart, lungs, and liver showed that
      respectively 99%, 88%, and 8% of the tissue radioactivity corresponded with the
      parent compound. Ligand 1b appears to be an excellent candidate for PET studies
      of mAChR receptors in heart and lungs.

PMID- 9016337
TI  - Diltiazem-like calcium entry blockers: a hypothesis of the receptor-binding site
      based on a comparative molecular field analysis model.
AB  - A series of 26 pyrrolo[2,1-c][1,4]benzothiazines, which have been already
      synthesized and reported to show calcium antagonist activity in both radioligand
      binding assays and functional studies, were investigated using the comparative
      molecular field analysis (CoMFA) paradigm. Due to the lack of experimental
      structural data on these derivatives, the minimum energy conformers obtained by
      molecular mechanics calculations were used in the subsequent study. Structures
      were aligned following an alignment criterion based on the pharmacophoric groups
      of the studied compounds. The predictive ability of the CoMFA model was evaluated
      using a test set consisting of three representative compounds. The best 3D
      quantitative structure-activity relationship model found yields significant cross
      validated, conventional, and predictive r2 values equal to 0.703, 0.970, and
      0.865, respectively, the average absolute error of predictions being 0.26 log
      unit. The predictive capability of this model was also tested on a further test
      set of molecules consisting of diltiazem and nine pyrrolo[2,1
      d][1,5]benzothiazepines endowed with calcium antagonist activity. The accurate
      results obtained also in this case revealed the robustness of the model. On the
      basis of the same alignment, the structural moieties of the studied calcium entry
      blockers which are thought to contribute to the biological activity were
      identified, and a possible receptor-binding site for all these compounds is
      presented taking into account the information derived from the analysis of the
      steric and electrostatic CoMFA contour maps.

PMID- 9016338
TI  - Mixed bis(thiosemicarbazone) ligands for the preparation of copper
      radiopharmaceuticals: synthesis and evaluation of tetradentate ligands containing
      two dissimilar thiosemicarbazone functions.
AB  - A series of four "mixed" bis(thiosemicarbazone) keto aldehyde derivatives
      containing dissimilar thiosemicarbazone functions were synthesized and evaluated
      as ligands for preparation of radiocopper-labeled radiopharmaceuticals. The
      pyruvaldehyde-based mixed bis(thiosemicarbazone) ligands
      CH3C[=NNHC(S)NH2]CH[=NNHC(S)NHMe] (4a), CH3C[=NNHC(S)NHMe]-CH[=NNHC(S)NH2] (4b),
      CH3C[=NNHC(S)NH2]CH[=NNHC(S)NMe2] (4c), and CH3C[=NNHC-(S)NHMe]CH[=NNHC(S)NMe2]
      (4d) were obtained by reaction of thiosemicarbazide, N4-methylthiosemicarbazide,
      or N4,N4-dimethylthiosemicarbazide with pyruvaldehyde 2-thiosemicarbazones that
      had been generated by oxidative cleavage of the appropriate pyruvic aldehyde
      dimethyl acetal 2-thiosemicarbazone. The 67Cu-labeled complexes of ligands 4a-d
      were prepared and screened in a rat model to assess the potential of each chelate
      as a 62Cu radiopharmaceutical for imaging with positron emission tomography. In
      the rat model the 67Cu complexes of ligands 4a-d exhibit significant uptake into
      the brain and heart after intravenous injection, following trends similar to
      those previously reported for the related bis(thiosemicarbazone) complexes, Cu
      PTS, Cu-PTSM, and Cu-PTSM2 (derived from pyruvaldehyde bis(thiosemicarbazone),
      pyruvaldehyde bis(N4-methylthiosemicarbazone), and pyruvaldehyde bis(N4,N4
      dimethylthiosemicarbazone), respectively). Ultrafiltration studies using
      solutions of dog and human serum albumin reveal that the 67Cu complexes of
      ligands 4a-d, like the Cu(II) complex of pyruvaldehyde bis(N4
      methylthiosemicarbazone), interact more strongly with human albumin than dog
      albumin.

PMID- 9016339
TI  - Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic
      receptors.
AB  - Ibogaine noncompetitively blocked (IC50 approximately 20 nM) 22NaCl influx
      through ganglionic-type nicotinic receptor channels of rat pheochromocytoma PC12
      cells. The major metabolite O-des-methylibogaine was 75-fold less active, and O-t
      butyl-O-des-methylibogaine was 20-fold less active. Ibogaine was relatively weak
      as a blocker (IC50 approximately 2000 nM) of the neuromuscular-type nicotinic
      receptor channels in human medulloblastoma TE671 cells. The blockade of nicotinic
      responses by ibogaine was only partially reversible in PC12 cells. In vivo,
      ibogaine at 10 mg/kg completely blocked epibatidine-elicited antinociception in
      mice, a response that is mediated by central nicotinic receptor channels. There
      was no significant blockade of the epibatidine response at 24 hr after the
      administration of 40 mg/kg ibogaine. The blockade of nicotinic channels could
      contribute to the antiaddictive properties of ibogaine.

PMID- 9016340
TI  - D1-like dopaminergic activation of phosphoinositide hydrolysis is independent of
      D1A dopamine receptors: evidence from D1A knockout mice.
AB  - Accumulated evidence suggests that dopamine and dopamine D1 agonists can activate
      phospholipase C in both brain and peripheral tissue. The receptor that mediates
      the hydrolysis of phosphoinositides has not been identified. The cloned dopamine
      D1A receptor that is generally thought to be linked to adenylyl cyclase, has also
      been proposed to couple to phospholipase C. However, a number of studies have
      suggested that this signaling pathway is mediated via a distinct D1-like dopamine
      receptor. We tested whether the D1A site plays a role in stimulating
      phosphoinositide hydrolysis by using the dopamine D1A-deficient mutant mice as a
      test model. Results show that although D1 dopamine receptor-mediated product on
      of cAMP is completely absent in membranes of D1A-deficient mice, D1 receptor
      mediated accumulation of inositol phosphate is identical in tissues of mutant and
      wild-type animals. Furthermore, the coupling of [3H]SCH23390 binding sites in
      striatal or frontal cortex membranes to G alpha s is markedly reduced, although
      coupling of [3H]SCH23390 binding sites to G alpha q was unaltered in tissue taken
      from D1A mutant mice compared with control animals. These results clearly
      demonstrate that dopaminergic stimulation of inositol phosphate formation is
      mediated by a D1 dopamine receptor subtype that is distinct from the D1A receptor
      that activates adenylyl cyclase.

PMID- 9016341
TI  - Role of determinants of cadmium sensitivity in the tolerance of
      Schizosaccharomyces pombe to cisplatin.
AB  - The genetic mechanisms underlying cisplatin (DDP) resistance in yeast were
      investigated by examining the cytotoxicity of DDP to Schizosaccharomyces pombe
      mutants that were either hypersensitive or resistant to Cd. Despite reports that
      have linked glutathione (GSH) to DDP resistance in human cancer cells, we found
      that a mutant of S. pombe that was hypersensitive to Cd by virtue of a 15-fold
      reduction in GSH level and lack of phytochelatin production was as tolerant as
      the wild-type strain to DDP. A mutant that harbored a mutation in hmt1, the gene
      encoding an ATP-binding cassette-type transporter for vacuolar sequestration of a
      phytochelatin/Cd complex, exhibited only mild hypersensitivity to DDP even though
      it was 100-fold more sensitive to Cd. Overexpression of hmt1 in wild-type or
      mutant cells conferred tolerance to Cd but failed to do the same for DDP.
      However, a strain that produced 6-fold more sulfide than wild-type cells was
      found to be 6-fold more resistant to DDP and twice as resistant to Cd; an
      association between DDP resistance and sulfide production was observed in three
      other strains that were examined, and overproduction of sulfide was accompanied
      by reduced platination of DNA. These results indicate that GSH and the GSH
      derived phytochelatin peptides do not play critical roles in determining
      sensitivity to DDP in S. pombe but rather identify increased production of
      sulfide as a possible new mechanism of DDP resistance that may also be relevant
      to human cells.

PMID- 9016342
TI  - Long-term blockade of serotonin reuptake affects synaptotagmin phosphorylation in
      the hippocampus.
AB  - Synaptic vesicle trafficking and transmitter release from presynaptic terminals
      are precisely regulated by a complex array of protein/protein interactions.
      Several of these proteins are substrates of endogenous protein kinases present in
      presynaptic terminals. The activity of Ca2+/calmodulin-dependent protein kinase
      II(CaMKII), one of the kinases involved in the modulation of transmitter release,
      was previously shown to increase in the hippocampus after long-term blockade of 5
      hydroxytryptamine (5-HT) reuptake (a treatment known to elicit an increase in 5
      HT release in this area). To investigate the changes induced in presynaptic
      protein phosphorylation by 5-HT reuptake blockade and concomitant CaMKII up
      regulation, we analyzed two major CaMKII presynaptic substrates (synapsin I and
      synaptotagmin). All 5-HT reuptake blockers that we used, which induce an increase
      in CaMKII activity and autophosphorylation, also caused a large (2-3-fold)
      increase in the Ca2+/calmodulin-dependent post hoc phosphorylation of
      synaptotagmin. Conversely, the phosphorylation of synapsin I is much less
      affected. The change in synaptotagmin phosphorylation, as determined through
      immunoprecipitation and quantitative immunoblot analysis after fluvoxamine
      treatment, is due exclusively to increased phosphate incorporation (presumably
      caused by the increased kinase activity) and not to a change in the level of
      substrate protein after the treatment. Thus, drugs known to induce an increase in
      5-HT release simultaneously induce an increase in the activity of presynaptic
      CaMKII and in the phosphate incorporation (post hoc) by a major CaMKII substrate
      in synaptic vesicles (synaptotagmin). This finding establishes a link between the
      facilitation of transmitter release induced by antidepressant drugs and the
      phosphorylation of synaptotagmin by CaMKII.

PMID- 9016343
TI  - Regulation of mouse neuropeptide Y Y1 receptor gene transcription: a potential
      role for nuclear factor-kappa B/Rel proteins.
AB  - We previously isolated a 1.3-kb genomic fragment in the 5'-flanking region of the
      murine neuropeptide Y (NPY) Y1 receptor gene, which is able to drive the
      expression of LacZ reporter gene in neuronal cells. We determined the ability of
      deletion mutants of this region to modulate transcription of the heterologous
      luciferase gene in the Y1 receptor-expressing neuroblastoma/ glioma NG108-15
      cells and the Y1 receptor-deficient 293 cells. Results suggest the presence of a
      cell type-specific core promoter (-399 to -218 from the initiator ATG) and,
      upstream, of two positive and two negative regulatory elements. Sequence analysis
      of the Y1 receptor promoter identified two decameric sequences corresponding to
      consensus binding sites for nuclear factor-kappa B/Rel proteins. Gel shift
      analysis indicated that a 29-bp oligonucleotide comprising the two putative kappa
      B sites, which we refer to as Y1-kappa B sequence, specifically binds kappa B
      related complexes in nuclear extracts from rat brain areas, NG108-15 cells, and
      the murine T cell clone A.E7. In nuclear extracts from A.E7 and NG108-15 cells,
      the Y1-kappa B sequence specifically binds an additional complex whose molecular
      nature remains to be elucidated. Through transient transfection studies, we also
      demonstrated that the Y1-kappa B sequence acts as an enhancer element, inferring
      its potential role in regulation of the Y1 receptor gene expression.

PMID- 9016344
TI  - Genetic alteration of alpha 2C-adrenoceptor expression in mice: influence on
      locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype
      nonselective alpha 2-adrenoceptor agonist.
AB  - alpha 2-Adrenergic receptors (alpha 2-ARs) regulate many physiological functions
      and are targets for clinically important antihypertensive and anesthetic agents.
      Three human and mouse genes encoding alpha 2-AR subtypes (alpha 2A, alpha 2B, and
      alpha 2C) have been cloned. We investigated the involvement of the alpha 2C-AR in
      alpha 2-adrenergic pharmacology by applying molecular genetic techniques to alter
      the expression of alpha 2C-AR in mice. The effects of dexmedetomidine, a subtype
      nonselective alpha 2-AR agonist, on monoamine turnover in brain and on locomotor
      activity were similar in mice with targeted inactivation of the alpha 2C-AR gene
      and in their controls, but the hypothermic effect of the alpha 2-AR agonist was
      significantly attenuated by the receptor gene inactivation. Correspondingly,
      another strain of transgenic mice with 3-fold overexpression of alpha 2C-AR in
      striatum and other brain regions expressing alpha 2C-AR showed normal reductions
      in brain monoamine metabolism and locomotor activity after dexmedetomidine, but
      their hypothermic response to the alpha 2C-AR agonists was significantly
      accentuated. The hypothermic effect of alpha 2-AR agonists thus seems to be
      mediated in part by alpha 2C-AR. Some small but statistically significant
      differences between the strains were also noted in brain dopamine metabolism.
      Lack of alpha 2C-AR expression was linked with reduced levels of homovanillic
      acid in brain, and mice with increased alpha 2C-AR expression had elevated
      concentrations of the dopamine metabolite compared with their controls.

PMID- 9016345
TI  - Synthesis and effect of nonhydrolyzable xanthosine triphosphate derivatives on
      prenylation of Rab5D136N.
AB  - A novel and convenient method for nucleoside triphosphate synthesis was applied
      to the preparation of potentially nonhydrolyzable xanthosine triphosphate
      derivatives. The N-methylimidazolide of xanthosine 5'-monophosphate reacted
      rapidly with methylenediphosphonic acid and imidodiphosphonic acid to give
      xanthosine 5'-(beta, gamma-methylene)triphosphate and xanthosine 5'-(beta, gamma
      imido)triphosphate, respectively, in good yields. Both compounds inhibited the
      xanthosine-diphosphate-dependent prenylation of a mutant of Rab5, Rab5D136N, the
      nucleotide specificity of which had been converted from GTP to xanthosine
      triphosphate. The results indicate that xanthosine 5'-(beta, gamma
      methylene)triphosphate and xanthosine 5'-(beta, gamma-imido)triphosphate bound to
      the mutant protein with similar affinities and were not hydrolyzed under the
      assay conditions. These novel derivatives may be useful tools for the study of
      the role of individual GTPases mutated to xanthosine triphosphate specificity in
      the background of other GTP-binding proteins.

PMID- 9016346
TI  - Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to
      inhibition by nonsteroidal anti-inflammatory drugs.
AB  - Aspirin (ASA) acetylates Ser516 of prostaglandin G/H synthase-2 (PGHS-2)
      resulting in a modified enzyme that converts arachidonic acid to 15(R)-hydroxy
      eicosatetraeroic acid [15(R)-HETE]. ASA has pharmacological benefits that may not
      all be limited to inhibition of prostaglandin synthesis, and this study was
      initiated to further investigate the properties of ASA-acetylated PGHS-2 and of
      the mutation of Ser516 to methionine, which mimics ASA acetylation. Both the
      S516M mutant and ASA-acetylated form of PGHS-2 (ASA-PGHS-2) synthesize 15(R)-HETE
      and have apparent K(m) values for arachidonic acid within 10-fold of the apparent
      K(m) value for untreated PGHS-2. The time courses of turnover-dependent
      inactivation were similar for reactions catalyzed by PGHS-2 and ASA-PGHS-2,
      whereas the PGHS-2(S516M) showed a decrease in both the initial rate of 15-HETE
      production and rate of enzyme inactivation. The production of 15-HETE by modified
      PGHS-2 was sensitive to inhibition by most nonsteroidal anti-inflammatory drugs
      (NSAIDs), including selective PGHS-2 inhibitors. As observed for the
      cyclooxygenase activity of PGHS-2, the inhibition of 15-HETE production by
      indomethacin was time-dependent for both ASA-PGHS-2 and PGHS-2(S516M). However,
      two potent, structurally related NSAIDs, diclofenac and meclofenamic acid, do not
      inhibit either ASA-PGHS-2 or the PGHS-2(S516M) mutant. These results demonstrate
      that the sensitivity to inhibition by NSAIDs of the 15-HETE production by ASA
      treated PGHS-2 is different than that of prostaglandin production by PGHS-2 and
      that Ser516 plays an important role in the interaction with fenamate inhibitors.
      The results also indicate that the conversion of arachidonic acid to 15-HETE by
      ASA-PGHS-2 is an efficient process providing a unique mechanism among NSAIDs that
      will not lead to arachidonic acid accumulation or shunting to other biosynthetic
      pathways.

PMID- 9016347
TI  - Substitution of charged amino acid residues in transmembrane regions 6 and 7
      affect ligand binding and signal transduction of the prostaglandin EP3 receptor.
AB  - Expression of the rabbit EP3 receptor isoform 77A in COS1 and HEK293tsA201 cells
      demonstrated specific binding of [3H]prostaglandin (PG)E2 and receptor-evoked
      decreases in intracellular cAMP levels. Competition binding with PGE2, PGE2
      methyl ester, misoprostol-free acid, misoprostol, and sulprostone suggested that
      a negative charge at the C1 position is essential for high affinity ligand
      binding and that the charge at this position is more important than steric bulk.
      Charged amino acid residues within the transmembrane (TM) domains of the receptor
      were mutated, and the resulting receptor proteins were analyzed for the effects
      of these mutations on receptor structure and/or function. Positively charged TM
      residues are candidates for interaction with the C1 carboxylic acid moiety of
      prostanoid ligands. Substitution of R329 (TM VII) with either alanine or
      glutamate resulted in a loss of both detectable [3H]PGE2 binding and receptor
      activation despite expression of the receptor protein as determined by
      immunoprecipitation and immunofluorescence. Substitution of K300 (TM V) with
      alanine had no effect on binding or signal transduction. Substitution of the
      conserved aspartic acid at position 338 (TM VII) with alanine caused a loss of
      detectable receptor-evoked inhibition of cAMP generation, although this mutation
      did not appreciably affect ligand binding. These studies suggest that R329 but
      not K300 is a key determinant in receptor/ligand interaction. Furthermore, D338
      plays a critical role in G1 activation by the EP3 receptor.

PMID- 9016348
TI  - Discordant hepatic expression of the cell division control enzyme p34cdc2 kinase,
      proliferating cell nuclear antigen, p53 tumor suppressor protein, and p21Waf1
      cyclin-dependent kinase inhibitory protein after WY14,643 ([4-chloro-6-(2,3
      xylidino)-2-pyrimidinylthio]acetic acid) dosing to rats.
AB  - The hepatocarcinogen and peroxisome proliferator WY14,643 ([4-chloro-6-(2,3
      xylidino)-2-pyrimidinylthio]acetic acid) was examined for its ability to induce
      changes in the intracellular protein expression of hepatic p34cdc2 kinase (CDK1),
      proliferating cell nuclear antigen (PCNA), p53 tumor suppressor protein, and
      p21Waf1 CDK inhibiting protein. Young adult male rats were administered 45 mg
      kg/day WY14,643 intraperitoneally for 1, 2, 3, 4, or 5 days or fed diets
      containing 0% or 0.08% WY14,643 for 1, 2, 3, or 4 weeks. WY14,643 dosing
      increased concentrations of hepatic proteins of 34- and 37-kDa molecular mass,
      which were identified through immunoprecipitation as CDK1 and PCNA, respectively.
      Gel filtration of the hepatic S9 fractions determined by enzyme-linked
      immunosorbent assay confirmed the increased expression of CDK1 and PCNA
      immunoreactivity in livers from WY14,643-treated rats. Also, gel filtration
      revealed that the native CDK1 and PCNA in hepatic S9 from WY14,643-treated rats
      chromatographed as a major peak with an apparent molecular mass of 70 and 76 kDa,
      respectively. Immunoblotting of the 70-kDa fraction with anti-CDK1 revealed a
      single band of molecular mass of 34 kDa. Thus, the CDK1 in the major
      immunoreactive peak of WY14,643-treated rat liver S9 seems to exist as a
      heterodimer or homodimer. Immunohistochemistry of formalin-fixed liver
      demonstrated a cytosolic localization of immunoreactive CDK1 and nuclear
      localization of immunoreactive PCNA in proliferating cells of WY14,643-treated
      rat livers. WY14,643 increased hepatic CDK1 content by 1.9-6.3-fold through
      postdosing days 1-5. Hepatic PCNA content was increased 1.9-5-fold over the same
      period. In the 4-week feeding study, CDK1 and PCNA expression were increased at
      all weekly time points by an average of 15-50-fold, respectively. Furthermore,
      the dietary administration of 0.08% WY14,643 resulted in sustained,
      overexpression of hepatic p53 tumor suppressor protein from week 1 through week 4
      and of p21Waf1 CDK inhibitory protein from week 3 to week 4.

PMID- 9016349
TI  - The majority of N-methyl-D-aspartate receptor complexes in adult rat cerebral
      cortex contain at least three different subunits (NR1/NR2A/NR2B).
AB  - A monoclonal antibody (R1JHL) against the NR1 subunit of the N-methyl-D-aspartate
      (NMDA) receptor has been developed that recognizes an epitope in the region of
      the amino-terminal amino acids 341-561 (a region common to all splice variants of
      NR1). This monoclonal antibody identifies a broad band at 115 kDa in immunoblots
      using membranes from NR1-transfected cells and from rat brain tissue. No cross
      reactivity with any NR2 subunit is seen. With the goal to determine
      quantitatively the subunit composition of cortical NMDA receptors, we used the
      monoclonal antibody to NR1 and polyclonal antibodies against the NR2A and NR2B
      subunits to perform immunoprecipitations of receptor subunits from solubilized
      adult rat cortical membranes. Solubilization of the receptor subunits was
      accomplished under both nondenaturing (native) conditions, under which the
      subunits seem to remain associated with one another, and denaturing conditions,
      under which the subunits are associated from each other. Although each of these
      antibodies selectively immunoprecipitates only its corresponding (cognate)
      subunit when the subunits have been solubilized under denaturing conditions, each
      of the antibodies immunoprecipitates a sizable fraction of the other two NMDA
      receptor subunits when membranes are solubilized under nondenaturing conditions,
      indicating an interaction in situ. Using quantitative immunoblot analysis of the
      three subunits in both the pellets and supernatants from the
      immunoprecipitations, we found 1) the dominant NMDA receptor complex in adult rat
      cortex contains at least three subunits, NR1/NR2A/NR2B; 2) a smaller fraction of
      NMDA receptors are composed of only two subunits, NR1/NR2B or NR1/NR2A; 3) there
      are no complexes that contain NR2A/NR2B that do not contain NR1; 4) only a small
      fraction of each subunit is not associated with any other NMDA receptor subunit;
      5) no coimmunoprecipitation of noncognate subunits occurs unless the subunits are
      assembled with each other in situ; and 6) there is no physical interaction
      between these NMDA receptor subunits and the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor GluR2 or GluR3 subunits. These results suggest
      that functional studies with recombinant receptors composed of at least three
      subunits may be the most physiologically meaningful.

PMID- 9016350
TI  - mu-Opioid receptor-stimulated guanosine-5'-O-(gamma-thio)-triphosphate binding in
      rat thalamus and cultured cell lines: signal transduction mechanisms underlying
      agonist efficacy.
AB  - G protein activation by different mu-selective opioid agonists was examined in
      rat thalamus, SK-N-SH cells, and mu-opioid receptor-transfected mMOR-CHO cells
      using agonist-stimulated guanosine-5'-O-(gamma-thio)-triphosphate ([35S]GTP gamma
      S) binding to membranes in the presence of excess GDP. [D-Ala2, N-MePhe4, Gly5
      ol]Enkephalin (DAMGO) was the most efficacious agonist in rat thalamus and SK-N
      SH cells, followed by (in rank order) fentanyl = morphine > > buprenorphine. In
      mMOR-CHO cells expressing a high density of mu receptors, no differences were
      observed among DAMGO, morphine or fentanyl, but these agonists were more
      efficacious than buprenorphine, which was more efficacious than levallorphan. In
      all three systems, efficacy differences were magnified by increasing GDP
      concentrations, indicating that the activity state of G proteins can affect
      agonist efficacy. Scatchard analysis of net agon stimulated [35S]GTP gamma S
      binding revealed two major components responsible for agonist efficacy
      differences. First, differences in the KD values of agonist-stimulated [35S]GTP
      gamma S binding between high efficacy agonists (DAMGO, fentanyl, and morphine)
      and classic partial agonists (buprenorphine and levallorphan) were observed in
      all three systems. Second, differences in the Bmax value of agonist-stimulated
      [35S]GTP gamma S binding were observed between DAMGO and morphine or fentanyl in
      rat thalamus and SK-N-SH cells and between the high efficacy agonists and
      buprenorphine or levallorphan in all three systems. These results suggest that mu
      opioid agonist efficacy is determined by the magnitude of the receptor-mediated
      affinity shift in the binding of GTP (or[35S]GTP gamma S) versus GDP to the G
      protein and by the number of G proteins activated per occupied receptor.

PMID- 9016351
TI  - Down-regulation of P2U-purinergic nucleotide receptor messenger RNA expression
      during in vitro differentiation of human myeloid leukocytes by phorbol esters or
      inflammatory activators.
AB  - HL-60 human promyelocytic leukocytes express G protein-coupled P2U-purinergic
      nucleotide receptors (P2UR or P2Y2R) that activate inositol phospholipid
      hydrolysis and Ca24 mobilization in response to ATP or UTP. We examined the
      expression of functional P2UR and P2UR mRNA levels during in vitro
      differentiation of HL-60 cells by dibutyryl-cAMP (Bt2cAMP), which induces a
      granulocyte/neutrophil phenotype, or by phorbol-12-myristate-13-acetate (PMA),
      which induces a monocyte/macrophage phenotype. Both P2UR function and P2UR mRNA
      levels were only modestly attenuated during granulocytic differentiation by
      Bt2cAMP. In contrast, P2UR function, as assayed by either Ca2+ mobilization or
      inositol trisphosphate generation, was greatly reduced in PMA-differentiated
      cells. This inhibition of P2UR function was strongly correlated with PMA-induced
      decreases in P2UR mRNA levels, as assayed by Northern blot analysis or reverse
      transcription-polymerase chain reaction-based quantification. Although PMA
      induced an early, transient up-regulation of P2UR mRNA, this was rapidly followed
      by a sustained decrease in P2UR mRNA to a level 5-10-fold lower than that in
      undifferentiated HL-60 cells. The half-life of the P2UR transcript in HL-60 cells
      was approximately 60 min, and this was not affected by acute exposure (< or = 4
      hr) to Bt2cAMP or PMA. PMA down-regulated P2UR mRNA in THP-1 monocytes and HL-60
      granulocytes but not in A431 human epithelial cells or human keratinocytes. P2UR
      mRNA was also down-regulated in THP-1 monocytes differentiated into inflammatory
      macrophages by gamma-interferon and endotoxin. These data indicate that myeloid
      leukocytes possess tissue-specific mechanisms for the rapid modulation of P2UR
      expression and function during differentiation and inflammatory activation.

PMID- 9016352
TI  - Characterization of recombinant human P2X4 receptor reveals pharmacological
      differences to the rat homologue.
AB  - We isolated a cDNA from human brain encoding a purinergic receptor that shows a
      high degree of homology to the rat P2X4 receptor (87% identity). By fluorescence
      in situ hybridization, the human P2X4 gene has been mapped to region q24.32 of
      chromosome 12. Tissue distribution analysis of human P2X4 transcripts
      demonstrates a broad expression pattern in that the mRNA was detected not only in
      brain but also in all tissues tested. Heterologous expression of the human P2X4
      receptor in Xenopus laevis oocytes and human embryonic kidney 293 cells evoked an
      ATP-activated channel. Simultaneous whole-cell current and Fura-2 fluorescence
      measurements in human embronic kidney 293 cells transfected with human P2X4 cDNA
      allowed us to determine the fraction of the current carried by Ca2: this was
      approximately 8%, demonstrating a high Ca2+ permeability. Low extracellular Zn2+
      concentrations (5-10 microM) increase the apparent gating efficiency of human
      P2X4 by ATP without affecting the maximal response. However, raising the
      concentration of the divalent cation (> 100 microM) inhibits the ATP-evoked
      current in a non-voltage-dependent manner. The human P2X4 receptor displays a
      very similar agonist potency profile to that of rat P2X4 (ATP > > 2-methylthio
      ATP > or = CTP > alpha, beta-methylene-ATP > dATP) but has a notably higher
      sensitivity for the antagonists suramin, pyridoxal-phosphate-6-azophenyl-2',4'
      disulfonic acid, and bromphenol blue. Chimeric constructs between human and rat
      isoforms as well as single-point mutations were engineered to map the regions
      responsible for the different sensitivity to suramin and pyridoxal-phosphate-6
      azophenyl-2'4'-disulfonic acid.

PMID- 9016353
TI  - Cloning and expression of rat metabotropic glutamate receptor 8 reveals a
      distinct pharmacological profile.
AB  - The metabotropic glutamate receptor (mGluR) cDNAs were originally cloned from
      rat, except for the mouse cDNA clone encoding mGluR8. Mouse mGluR8 couples weakly
      to the inhibition of adenylate cyclase, thus hindering the characterization of
      its pharmacological properties. We isolated a rat mGluR8 cDNA that encodes a
      protein of 908 amino acids. In situ hybridization revealed prominent mGluR8 mRNA
      expression in olfactory bulb, pontine gray, lateral reticular nucleus of the
      thalamus, and piriform cortex. Less abundant expression was detected in cerebral
      cortex, hippocampus, cerebellum, and mammillary body. Glutamate evoked pertussis
      toxin-sensitive potassium currents in Xenopus laevis oocytes coexpressing mGluR8
      and G protein-coupled inwardly rectifying potassium channels. mGluR8 was also
      activated by the group III-specific agonist L-2-amino-4-phosphonobutyric acid;
      (2(S), 1'(S), 2'(S)]- 2-(carboxycyclopropyl)glycine, which has been frequently
      used as a selective group II agonist; and the nonselective agonist (1(S), 3(R)]-1
      aminocyclopentane-1,3-dicarboxylic acid but not by the group I-specific agonist
      3,5-dihydroxyphenylglycine or the group II-specific agonist [2(S), 1'(R), 2(R),
      3'(R)]-2-(2, 3-dicarboxycyclopropyl)glycine. The agonist profile in order of
      potency was [2(S), 1'(S), 2'(S)]-2-(carboxycyclopropyl)glycine approximately L-2
      amino-4-phosphonobutyric acid > glutamate > > [1(S), 3(R)]-1-aminocyclopentane-1,
      3-dicarboxylic acid, with EC50 values of 0.63, 0.67, 2.5, and 47 microM,
      respectively. Both the group I/II-specific antagonist (R,S)-alpha-methyl-4
      carboxyphenylglycine and the group III-specific antagonist alpha-methyl-amino
      phosphonobutyrate inhibited mGluR8. The pharmacological profile of mGluR8 is
      distinct among mGluRs but closely matches that of presynaptic inhibition in some
      central nervous system pathways. Thus, cellular responses mediated by both group
      II and III agonists may in some cases reflect activation of mGluR8 rather than
      multiple mGluR subtypes.

PMID- 9016354
TI  - Inhibition of the cardiac sarcolemma Na+/Ca2+ exchanger by conformationally
      constrained small cyclic peptides.
AB  - Positively charged cyclic peptides (three to seven amino acids) have been tested
      for their inhibitory effects on Na+/Ca2+ exchange in the cardiac sarcolemma
      vesicles. The lead structure of Phe-Arg-Cys-Arg-Cys-Phe-CONH2 (FRCRCFa) has been
      systematically modified for identification of important pharmacophores. In cyclic
      peptides (intramolecular S-S bond, the carboxyl terminal is locked with amide
      (CONH2), and positive charge is retained by one or two arginines, ornithines, or
      lysines. Thirty-five different cyclic peptides show IC50 values in the range of 2
      800 microM, suggesting that some specific structure-activity relationships may
      determine the inhibitory effects. Shortening of the FRCRCFa length to four amino
      acids decreases the inhibitory potency by 10-80-fold. The substitution of Arg2 or
      Arg4 in FRCRCFa with lysine or ornithine decreases the inhibitory potency by 5-12
      fold, suggesting that both arginines are beneficial for inhibition. The
      substitution of Phe1 in FRCRCFa by 1,2,3,4-tetrahydroisoquinoline-3-carboxylic
      acid produces a potent inhibitor (IC50 = 2-4 microM). The N-myristoylated FRCRCFa
      exhibits an inhibitory potency (IC50 = 8-10 microM) similar to that of the parent
      FRCRCFa peptide, thereby arousing a new possibility for the development of a cell
      permeable blocker of the Na+/Ca2+ exchanger, D-Arg4 or D-Cys5 substitutions in
      FRCRCFa do not alter the inhibitory effect, whereas the L-to-D substitutions of
      other amino acids in FRCRCFa reduce the inhibitory potency by 4-5-fold. Thus, the
      L-to-D substitutions of Arg4 and/or Cys5 have a potential to increase the peptide
      stability to proteolytic degradation. The insertion of proline outside of the
      ring of FRCRCFa diminishes the inhibitory potency by 3-6-fold, whereas proline
      introduction into the ring decreases the inhibitory potency by 16-20-fold. The
      replacement of Cys3 and Cys5 in FRCRCFa with beta, beta-dimethylcystein has no
      significant effect on the inhibitory potency, suggesting that the S-S bond is not
      exposed to the interface of the peptide/receptor interaction. In conclusion, the
      current data support a proposal that the conformationally constrained Arg-Cys-Arg
      Cys structure is obligatory for inhibition of Na+/Ca2+ exchange, whereas
      hydrophobic additions at the carboxyl and amino ends have limited effects in
      increasing the inhibitory potency.

PMID- 9016355
TI  - Lack of enantiospecificity of human 2'-deoxycytidine kinase: relevance for the
      activation of beta-L-deoxycytidine analogs as antineoplastic and antiviral
      agents.
AB  - We demonstrate that human 2'-deoxycytidine kinase (dCK) is a nonenantioselective
      enzyme because it phosphorylates beta-D-2'-deoxycytidine (D-dCyd), the natural
      substrate, and beta-L-2'-deoxycytidine (L-dCyd), its enantiomer, with the same
      efficiency. Kinetic studies showed that L-dCyd is a competitive inhibitor of the
      phosphorylation of D-dCyd with a Kl value of 0.12 microM, which is lower than the
      K(m) value for D-dCyd (1,2 microM). Chemical modifications of either the base or
      the pentose ring strongly decrease the inhibitory potency of L-dCyd, L-dCyd is
      resistant to cytidine deaminase and competes in cell cultures with the natural D
      dCyd as substrate for dCK, thus reducing the incorporation of exogenous [3H]dCyd
      into DNA. L-dCyd had no effect on the pool of dTTP deriving from the salvage or
      from the de novo synthesis, does not inhibit short term RNA and protein
      syntheses, and shows little or no cytotoxicity. Our results indicate a catalytic
      similarity between human dCK and herpetic thymidine kinases, enzymes that also
      lack stereospecificity. This functional analogy underlines the potential role of
      dCK as activator of L-deoxycytidine analogs as antiviral and antineoplastic
      agents and lends support to the hypothesis that herpesvirus thymidine kinase
      might have evolved from a captured cellular dCK gene, developing the ability to
      phosphorylate thymidine and retaining that to phosphorylate deoxycytidine.

PMID- 9016356
TI  - Aminoacyl and peptidyl analogs of chloramphenicol as slow-binding inhibitors of
      ribosomal peptidyltransferase: a new approach for evaluating their potency.
AB  - In a model system derived from Escherichia coli, acetylphenylalanyl-puromycin is
      produced in a pseudo-first-order reaction between the preformed
      acetylphenylalanyl/tRNA/poly(U)/ribosome complex (complex C) and excess
      puromycin. Two aminoacyl analogs [3, Gly-chloramphenicol (CAM): 4, L-Phe-CAM] and
      two peptidyl analogs (2, L-Phe-Gly-CAM: 5, Gly-Phe-CAM) of CAM (1) were tested as
      inhibitors in this reaction. Detailed kinetic analysis suggests that these
      analogs (I) react competitively with complex C and form the complex C*l, which is
      inactive toward puromycin. C*l is formed via a two-step mechanism in which C*l is
      the product of a slow conformational change of the initial encounter complex Cl
      according to the equation C + l reversible Cl reversible C*l. Furthermore, we
      provide evidence that analog 5 may react further with C*l forming the species
      C*l2. The values of the apparent association rate constant (K(assoc)) are 1.42 x
      microM-1 min-1 for 2, 0.55 x microM-1 min-1 for 3, and 0.18 x microM-1 min-1 for
      4 and 0.038 x microM-1 min-1 for 5 [corrected]. In the case of analog 5, K(assoc)
      is a linear function of the inhibitor concentration; when [I] approaches zero,
      the K(assoc) value is equal to 3.8 x 10(2) M-1 sec-1. Such values allow the
      classification of CAM analogs as slow-binding inhibitors. According to K(assoc)
      values, we could surmise that analog 2 is 2.5-fold more potent than 3 and 8-fold
      more potent than 4. The relative potency of analog 5 is the lowest among the
      analogs and is dependent on its concentration. The results are compared with
      previous data and discussed on the basis of a possible retro-inverso relationship
      between CAM analogs and puromycin.

PMID- 9016357
TI  - Evidence for a role of a perferryl-oxygen complex, FeO3+, in the N-oxygenation of
      amines by cytochrome P450 enzymes.
AB  - Most cytochrome P450 (P450)-catalyzed reactions are believed to involve an FeO3+
      intermediate as the actual oxygenating species. However, studies on the mechanism
      of steroid aromatization and subsequent model work have provided evidence that a
      peroxo-iron form (formally FeO2) can be involved directly in some oxidations. The
      possible involvement of peroxoiron was considered in P450-catalyzed N
      oxygenations, because there is precedent for the use of H2O2 and organic
      peroxides in such reactions in the literature concerning synthetic and flavin
      reactions. The approach used was to compare P450 reactions involving the normal
      NADPH/NADPH-P450 reductase/O2 system with those supported by the oxygen
      surrogates H2O2 (which can directly form FeO2 and subsequently FeO3+) and
      iodosylbenzene (which can form FeO3 but not FeO2+). Iodosylbenzene was effective
      in supporting rabbit P450 1A2-catalyzed N,N-dimethyl-2-aminofluorene N
      oxygenation, human P450 3A4-catalyzed quinidine N-oxygenation, rat P450 2B1
      catalyzed oxidation of N-benzyl-(1-phenyl) cyclobutylamine to the N-hydroxyamine
      and nitrone, and rat P450 2B1-catalyzed and rabbit P450 2B4-catalyzed N
      oxygenation of N,N-dimethylaniline (also N-demethylation). H2O2 also supported
      most of these reactions. A mutant of P450 2B4 with the substitution of alanine
      for threonine at position 302 has been shown to have decreased ability to
      catalyze reactions involving the putative FeO3+ but, presumably because of
      decreased ability to protonate the FeO2+ complex, to have enhanced activity in
      oxidative deformylation reactions believed to involve FeO2+. This mutant showed
      both decreased N,N-dimethylaniline N-demethylation and N-oxygenation activity.
      Although some contribution of an FeO2+ species to these reactions cannot be ruled
      out, formation of product in the iodosylbenzene-supported systems cannot be
      readily explained by an obligatory FeO2 mechanism and the involvement of FeO3+ is
      concluded to be more likely.

PMID- 9016358
TI  - Agonist activation of delta-opioid receptor but not mu-opioid receptor
      potentiates fetal calf serum or tyrosine kinase receptor-mediated cell
      proliferation in a cell-line-specific manner.
AB  - Activation by opioid receptors of cell proliferation was examined with fibroblast
      cell lines stably expressing either delta-opioid or mu-opioid receptors. Addition
      of [D-Ala2, D-Leu5]-enkephalin or [D-Pen2,D-Pen5]-enkephalin to Chinese hamster
      ovary (CHO) cells transfected with delta-opioid receptor cDNA resulted in an
      agonist concentration-dependent potentiation of fetal calf serum (FCS)-stimulated
      cell proliferation. This potentiation by delta-opioid agonists was antagonized by
      naloxone and was not observed with the kappa-opioid receptor selective agonist
      U50,488 or the mu-opioid receptor selective agonist [D-Ala2,N-MePhe4, Gly-ol5]
      enkephalin. This delta-opioid agonist effect was not observed at FCS
      concentrations > 0.1% and could be blocked by pretreating cells with pertussis
      toxin, indicating that Gi/Go were involved in this action. In addition, delta
      opioid agonists could potentiate CHO cell proliferation stimulated by those
      growth factors that are mediated by tyrosine kinase receptors (i.e., insulin,
      insulin-like growth factor 1, and fibroblast-derived growth factor b). This delta
      opioid agonist potentiation of growth apparently was dependent on the level of
      delta-opioid receptors that were expressed and had cell-line selectivity.
      Activation of delta-opioid receptors expressed in Rat-1 or NIH3T3 fibroblast did
      not result in a modulation of the cell growth induced by FCS or by growth
      factors. Interestingly, in CHO cells transfected with mu-opioid receptor cDNA,
      activation with agonists did not produce a potentiation of FCS-stimulated
      proliferation. This lack of mu-opioid receptor effect was not due to the
      differences among CHO clones. In a CHO cell line transfected with both delta
      opioid receptor cDNA and mu-opioid receptor cDNA, activation of delta-but not mu
      opioid receptors resulted in a potentiation of growth. These data suggest that
      delta- and mu-opioid receptors in CHO cells activate similar but divergent second
      messenger pathways, resulting in the differential regulation of cell growth.

PMID- 9016359
TI  - Mechanism of phosphorylation-recognition by visual arrestin and the transition of
      arrestin into a high affinity binding state.
AB  - Arrestin plays an important role in quenching phototransduction via its ability
      to interact specifically with the phosphorylated light-activated form of the
      visual receptor rhodopsin (P-Rh*). Previous studies have demonstrated that Arg175
      in bovine arrestin is directly involved in the phosphorylation-dependent binding
      of arrestin to rhodopsin and seems to function as a phosphorylation-sensitive
      trigger. In this study, we further probed the molecular mechanism of
      phosphorylation recognition by substituting 19 different amino acids for Arg175.
      We also assessed the effects of mutagenesis of several other highly conserved
      residues within the phosphorylation-recognition region (Val170, Leu172, Leu173,
      Ile174, Val177, and Gln178). The binding of all of these mutants to P-Rh*, light
      activated rhodopsin, and truncated rhodopsin, which lacks the carboxyl-terminal
      phosphorylation sites, was then characterized. Overall, our results suggest that
      arrestin interaction with the phosphorylated carboxyl-terminal domain of
      rhodopsin activates two relatively independent changes in arrestin: (a)
      mobilization of additional binding sites and (b) increased affinity of the
      phosphorylation-recognition region for the rhodopsin carboxyl-terminal domain.
      Together, these two mechanisms ensure the exquisite selectivity of arrestin
      toward P-Rh*. Mutagenesis of residues that play a major role in binding site
      mobilization and phosphorylation-recognition enabled us to create "constitutively
      active" (phosphorylation-independent) arrestin mutants that have high affinity
      for both P-Rh* and light-activated rhodopsin. The introduction of a negative
      charge in position 175 was particularly effective in this respect. A detailed
      molecular model of phosphorylation-recognition is proposed.

PMID- 9016360
TI  - Interethnic variability in birth weight and genetic background: a study of
      placental alkaline phosphatase.
AB  - The relationship between human placental alkaline phosphatase (PLAP) genotype and
      birth weight is investigated in a sample of white, black and Puerto-Rican new
      born infants from New Haven, Connecticut (total 710 subjects). Black and Puerto
      Rican infants show a higher incidence of growth retardation and a higher
      frequency of ALPp*1/*1 genotype as compared to whites. The proportion of newborns
      with a low birth weight (below the 10th percentile) is lower in infants with
      ALPp*1/*1 genotype than in those with other PLAP genotypes, especially among non
      whites. It is argued that the higher frequency of ALPp*1 allele among non-whites
      might be, at least in part, a consequence of their adaptation in the past to
      environmental conditions adverse to optimal intrauterine development.

PMID- 9016361
TI  - Evolution of human growth spurts.
AB  - This study investigates subadult growth spurts in a large sample of anthropoid
      primates, including humans. Analyses of body mass growth curves show that humans
      are not unique in the expression of female and male body mass growth spurts.
      Subadult growth spurts are observed in both New World and Old World anthropoid
      primates and are more common in males than in females. Allometric analyses of
      growth spurts indicate that many aspects of primate growth spurts are strongly
      correlated with species size. Small species tend not to exhibit growth spurts.
      Although male and female scaling patterns for velocity and size measures are
      comparable, scaling relations of variables that measure the timing of growth
      spurts differ by sex. These patterns can be related to sexual differences in life
      histories. Scaling analyses further show that humans do not depart substantially
      from patterns that describe other anthropoid primates. Thus, in relative terms,
      human growth spurts are not exceptional compared to this sample of primates. The
      long absolute delay in the initiation of the human growth spurt may be of
      substantial evolutionary importance and serves to distinguish humans from other
      primates. In essence, humans exhibit growth spurts that are comparable to other
      primates in many respects. However, human growth spurts are shifted to very late
      absolute ages.

PMID- 9016362
TI  - Dental effects of diet and coca-leaf chewing on two prehistoric cultures of
      northern Chile.
AB  - Two ancient cultures of northern Chile, the Chinchorro (9000-3500 BP) and the
      Maitas Chiribaya (850-700 BP) were examined for dental pathology in search of
      possible correlations between dental health, diet, and the cultural practice of
      coca-leaf chewing. The Chinchorro occupied the river mouth of the Azapa valley,
      subsisting almost exclusively on a maritime economy. The Maitas Chiribaya,
      descendants of migrant highlanders, had a rather well-developed agricultural
      subsistence base. The Chinchorro demonstrated extreme attrition rates and a
      correspondingly high frequency of periapical abscesses. They were essentially
      caries-free and enjoyed a moderate antemortem tooth loss frequency. The Maitas
      Chiribaya suffered light attrition; a high caries frequency, especially at the
      cementoenamel junction of crown and root, and a remarkably high antemortem tooth
      loss frequency. The cultural practice of coca-leaf chewing is implicated in the
      excessive posterior edentulism of the Maitas Chiribaya.

PMID- 9016363
TI  - Psoriatic arthritis in a fifth-century Judean Desert monastery.
AB  - Psoriatic arthritis is a greatly underreported seronegative erosive arthropathy,
      due to the ambiguous lesions it leaves on bone in all but the most severe cases.
      For a confident diagnosis of psoriatic arthritis to be made, sacroiliac and
      intervertebral joint fusion must be present together with erosive lesions of the
      peripheral skeleton including most especially the terminal interphalangeal
      joints. In modern times it is only a small percentage of cases who experience
      such debilitating disease, which may explain who so few cases of psoriatic
      arthritis can confidently be identified from past populations. This report
      describes this pathological condition as observed in the comingled skeletal
      remains of nine males and one female from the tomb of Paulus in the Byzantine
      Monastery of Martyrius, in the Judean Desert. Visual study was complemented using
      radiographic techniques along with scanning electron microscopy. Two adult males
      show characteristic lesions of psoriatic arthritis, demonstrating the form known
      as arthritis mutilans. A third individual shows less widespread erosive lesions
      which may signify a pauciarticular example of psoriatic arthritis, as is true of
      most cases in modern times, or the remains may represent Reiter's disease. During
      the Byzantine period the earlier practise of expelling those with disfiguring
      diseases (biblical leprosy) evolved into a philanthropic, caring philosophy where
      the sick were housed and fed out of charity, often within monasteries. The
      presence of these cases of psoriatic arthritis within such a Judean Desert
      monastery confirms earlier suggestions that psoriasis was one of the diseases
      included by those in the ancient eastern Mediterranean under the umbrella term of
      biblical leprosy.

PMID- 9016364
TI  - The M. obturator internus sulcus on middle and late Pleistocene human ischia.
AB  - Recent human ischia and those of Middle and Late Pleistocene hominids exhibit
      variation in the cranio-caudal location of the sulcus for the internal obturator
      muscle as it rounds the ischium through the lesser sciatic notch, from being
      fully cranial of the ischial tuberosity, to bordering the tuberosity, to crossing
      the superior tuberosity. Among two recent human samples, all three forms exist,
      with the cranial position of the sulcus being more common in a 20th century
      Euroamerican sample whereas the intermediate one predominates in a horticultural
      late prehistoric Amerindian sample. The available Pleistocene Homo fossil remains
      exhibit the full range of variation with no one form being dominant in Middle
      Pleistocene archaic humans and Middle Paleolithic late archaic and early modern
      humans. It is only within the Upper Paleolithic that the cranial and intermediate
      locations for the sulcus become predominant. These patterns therefore indicate
      that it is inappropriate to use this feature for distinguishing later Pleistocene
      hominid groups.

PMID- 9016365
TI  - Maximum walking speed and lower limb length in hominids.
AB  - In 1984, Helene (Am.J. Physics 52:656) and Alexander (Am. Scientist 72:348-354)
      presented equations which purported to explain how lower limb length limited
      maximum walking speed in humans. The equations were based on a simplified model
      of human walking in which the center of mass (CoM) "vaults" over the supporting
      leg. Increasing walking speed by increasing stride frequency or stride length
      would increase the upward acceleration of the CoM in the first half of stance
      phase, to the point that it would be greater than the downward pull of gravity,
      and the individual would become airborne. This constitutes running by most
      definitions. While these models ignored various mechanical factors, such as knee
      flexion during midstance, that reduce the vertical movement of the CoM, the
      general idea is plausible inasmuch as the CoM of the body does oscillate
      vertically with each step. One hypothesis tested here is whether it is indeed the
      interaction between the pull of gravity and the individual's own upward
      acceleration that determines at what speed (or cadence) he changes from walking
      to running. Another hypothesis considered is that increased lower limb length (L)
      was selected for in early hominids, because of the locomotor advantages of longer
      lower limbs. Results indicate, however, that while L was clearly related to
      maximum possible walking speed, it was not an important factor in determining
      maximum "comfortable" walking speed. These and other results from the recent
      literature suggest that increased lower limb length provided no selective
      advantage in locomotion, and other explanations should be sought.

PMID- 9016366
TI  - Dental microwear and microstructure in early oligocene primates from the Fayum,
      Egypt: implications for diet.
AB  - Textbook descriptions usually portray the Fayum anthropoideans as frugivores,
      with Parapithecus grangeri including a folivorous component in its diet and
      Apidium a component of hard-object feeding. Recent work with modern mammals has
      shown that analyses of both dental microwear and dental microstructure may yield
      insights into diet and tooth use. The purpose of this study was to combine these
      two techniques to gain a better perspective on the paleobiology of the Fayum
      higher primates. Dental microwear analyses involved the use of high resolution
      epoxy casts of Aegyptopithecus, Parapithecus, and Apidium housed in the Duke
      University Primate Center. Scanning electron micrographs were taken at x500, and
      all microwear features in each micrograph were digitized. For microstructure
      analyses, molar teeth were sectioned in a variety of planes, lightly etched, and
      photographed in the SEM. Results of the dental microwear analyses indicate that
      the three Fayum anthropoideans all clustered with modern primate frugivores but
      that there were also significant differences between Aegyptopithecus and the
      other two Fayum genera. By contrast, dental microstructure analyses showed
      important differences between Apidium and the other two genera. The reason for
      these differences probably lies in a combination of body size and dietary
      differences, with Aegyptopithecus occasionally feeding on hard objects and
      Apidium maximizing wear resistance through a unique emphasis of radial (rather
      than decussating) enamel.

PMID- 9016367
TI  - Mandibular ramus flexure--indicator of sexual dimorphism?

PMID- 9016368
TI  - Overview of pulmonary complications.
AB  - Pulmonary diseases continue to be important causes of illness and death in
      patients with HIV infection, but changes in therapy and demographics of HIV
      infected populations are changing their manifestations. The risk of developing
      specific disorders is related to the area of residence, degree of
      immunosuppressions, HIV risk group, and use of prophylactic therapies. Bronchitis
      and sinusitis occur commonly in the general population but more frequently in HIV
      infected persons. The increasing population of HIV-infected drug users is
      reflected in the increasing incidence of bacterial pneumonia and tuberculosis.
      Antipneumocystis prophylaxis has reduced the incidence of and mortality rate from
      this infection, and adjunctive corticosteriod therapy has improved the outlook
      for respiratory failure. Increased longevity, however, carries the risk of
      developing other opportunistic infections and neoplasms, some previously rare in
      AIDS.

PMID- 9016369
TI  - Immunologic effects of HIV in the lung.
AB  - This article covers a selected group of topics dealing with the contribution of
      lung immunocompetent cells in the host defense mechanisms against HIV. These
      include recent findings suggesting that bidirectional signals between alveolar
      macrophages and pulmonary cytotoxic T lymphocytes define regulatory networks,
      which contribute to the accumulation of HIV-specific effector cells in the lung
      microenvironment. The authors also emphasize the cell pattern of HIV infection in
      the lung, highlighting the role of the retrovirus in weakening pulmonary host
      defenses and its spreading into the lower respiratory tract.

PMID- 9016370
TI  - Treatment of HIV infection and its complications.
AB  - Because the AIDS epidemic continues to grow, there is a sense of urgency to
      develop new treatment strategies, both for HIV infection and for AIDS-related
      illnesses. The rapid gathering of basic information related to HIV type 1 biology
      and opportunistic infections has led to an explosion in physicians' ability to
      diagnose, prevent, and treat HIV disease and its associated complications.
      Research in this rapidly evolving field is likely to lead to further advances in
      the months and years that follow.

PMID- 9016371
TI  - Pneumocystis carinii.
AB  - Improved understanding of Pneumocystis carinii, in particular the widespread use
      of chemoprophylaxis, has resulted in a declining incidence of infection in
      patients infected with HIV since the late 1980s. Despite these advances, P.
      carinii pneumonia continues to represent an important cause of pulmonary disease
      in HIV-seropositive individuals who do not receive chemoprophylaxis or when
      breakthrough episodes occur. This article reviews the history, biology, clinical
      manifestations, prognostic markers, therapy, and chemoprophylaxis of P. carinii
      pneumonia in HIV-seropositive patients.

PMID- 9016372
TI  - Mycobacterial complications of HIV infection.
AB  - Tuberculosis is the most common opportunistic infection worldwide and is caused
      by the only readily transmissible pathogen among persons with HIV infection. If
      treatment is initiated promptly and is supervised appropriately, cure,
      fortunately, is highly likely. Isoniazid preventive therapy substantially reduces
      the risk of tuberculosis in persons with HIV infection. Of the nontuberculous
      mycobacteria, Mycobacterium avium complex (MAC) is the most frequent cause of
      disease; however, disseminated MAC disease usually is not seen until the CD4+
      cell count is less than 50 cells/L. Newer agents, such as the macrolides and
      rifabutin, form the nucleus of treatment regimens and also are effective in
      preventing the disease.

PMID- 9016373
TI  - Bacterial pneumonia associated with HIV-1 infection.
AB  - Bacterial pneumonia remains an important cause of treatable morbidity among HIV-1
      infected persons. These pneumonias occur at all CD4 counts but are especially
      common as the HIV-1 infection progresses. Bronchopneumonia should be considered
      particularly in the setting of segmental or lobar consolidation associated with
      productive cough and fever. S. pneumoniae remains the most common pathogen
      causing bronchopneumonia. Because of the high rate of bacteremia, diagnosis may
      be facilitated by blood cultures. Treatment is similar to management of HIV-1
      seronegative persons, although drug resistance against some bacteria may be an
      emerging problem. Several opportunities exist for prevention, and these should be
      pursued vigorously.

PMID- 9016374
TI  - Fungal pulmonary complications.
AB  - With AIDS has come a new level of T-cell immunosuppression, beyond that
      previously seen. The impact of the HIV pandemic on the field of fungal infections
      includes a major increase in the number of serious fungal infections, an increase
      in the severity of those infections, and even some entirely new manifestations of
      fungal illness. In this article fungal pulmonary complications of AIDS are
      discussed. T-cell opportunists including Cryptococcus neoformans and the endemic
      mycoses are the most important pathogens. Phagocyte opportunists, including
      Aspergillus species and agents of mucormycosis, are less important.

PMID- 9016375
TI  - Viruses and other miscellaneous organisms.
AB  - Pulmonary infections caused by several types of viruses and other miscellaneous
      organisms may cause disease in HIV infection. Evidence suggests that pulmonary
      conditions may result from infections of the lung by HIV itself. Other viruses,
      most commonly cytomegalovirus, may be primary perpetrators of pneumonitis or may
      contribute to diseases caused by coexisting infections. Although diagnosis and
      assessment of the clinical significance of these infections may be difficult,
      their recognition is of practical importance because potentially effective
      therapeutic agents are available for several of them. Miscellaneous infections
      such as pulmonary toxoplasmosis and pertussis are other uncommon but potentially
      treatable complications of HIV disease.

PMID- 9016376
TI  - Pulmonary complications of HIV-associated malignancies.
AB  - Approximately 25% of patients infected with HIV will develop malignancies, most
      commonly Kaposi's sarcoma and non-Hodgin's lymphoma. These tumors can involve the
      lung, causing significant morbidity and mortality. This article discusses the
      clinical presentation, diagnosis, and treatment of the pulmonary complications of
      the malignancies associated with HIV infection.

PMID- 9016377
TI  - Lymphocytic interstitial pneumonitis and nonspecific interstitial pneumonitis.
AB  - Nonspecific interstitial pneumonitis (NIP) and lymphocytic interstitial
      pneumonitis (LIP), with or without lymphocytic alveolitis, are poorly understood
      pulmonary complications of HIV infection. These disorders probably represent a
      spectrum of lymphoproliferative processes that overlap, rather than distinct
      illnesses. The clinical presentation, radiographic findings, and physiologic
      abnormalities in NIP and LIP are not specific and therefore require a biopsy for
      definitive diagnosis. The clinical course of these illnesses is generally
      favorable, even without specific treatment.

PMID- 9016379
TI  - HIV in children.
AB  - Because children acquire HIV infection differently than adults, this article
      begins with a discussion of the epidemiology of AIDS in children. This is
      followed by a discussion of factors related to progression of the disease and
      survival in pediatric AIDS. A discussion of the pulmonary manifestations in
      children is followed by a suggested approach to the HIV-infected child with
      respiratory symptoms.

PMID- 9016378
TI  - Approach to the patient with pulmonary disease.
AB  - The approach to the HIV-infected patient with pulmonary disease is summarized by
      the algorithms in Figures 3 and 4. These are not intended to be followed in a
      rigid step-wise fashion. Rather, the practitioner's knowledge of the patient with
      his or her accompanying medical risks influences the path taken, including the
      depth and the speed of the evaluation. For example, the patient with cough who is
      afebrile and breathing at 18 breaths a minute, with a normal chest radiograph and
      a CD4 count of 350 cells/mm3, is reasonably treated with a macrolide or
      cephalosporin for bacterial bronchitis and clinical follow-up while awaiting
      cultures (see Fig. 4). A febrile patient with a cough productive of thin mucus,
      but known to have a CD4 count of 60 cells/mm3 should be started on anti-PCP
      therapy while being evaluated for PCP with an induced sputum and if
      nondiagnostic, a bronchoscope despite a normal chest radiograph. Screening can be
      as simple as placing an oximeter on the patient's finger in the clinic. If the
      oxygen saturation of a patient with a normal chest radiograph is low, then the
      patient should be hospitalized and begun on treatment for PCP while diagnostic
      evaluation is initiated. If the oxygen saturation is normal, the patient can be
      exercised to elicit desaturation. If there is no desaturation, PCP is unlikely.
      If the results are equivocal (i.e., a decrease in saturation, but less than 3%),
      rest and exercise arterial blood gases can be performed, along with a Dlco
      Gallium scanning can be done in patients known to have abnormal Dlco or those who
      cannot exercise. Patients with focal infiltrates who have acute onset of symptoms
      (see Fig. 4) commonly have bacterial infections, but the possibility of PCP or TB
      should not be dismissed. Induced sputum should be examined if TB or PCP is
      suspected. Patients who are severely ill might go quickly to bronchoscopy without
      awaiting improvement on empiric therapy. The patient with diffuse infiltrates
      (see Fig. 4) needs no screening because the presence of disease is apparent from
      the radiograph. The diagnostic part quickly leads to bronchoscopy for these
      patients and the initiation of therapy for PCP when suspected. In patients with
      known pulmonary KS, gallium scanning can be helpful to rule out acute infection,
      but bronchoscopy is warranted if the patient is severely ill, or at high risk for
      PCP. This approach should avoid unnecessary procedures in patients with simple
      bacterial infections, without missing opportunistic infections and tumors.

PMID- 9016380
TI  - HIV in illicit drug users.
AB  - Illicit drug users comprise a substantial and growing proportion of the HIV
      infected population. Although they develop pulmonary complications common to all
      HIV transmission groups, they also have unique respiratory illnesses due to the
      direct effect of the illicit drugs on the lung. Bacterial infections,
      tuberculosis, and noninfectious complications all have a major effect on
      morbidity and mortality in this portion of the HIV-infected population.

PMID- 9016381
TI  - Current applications of polysaccharides in colon targeting.
AB  - Polysaccharides have over the years been used widely in pharmaceutical, chemical,
      and biochemical drug delivery. This family of natural polymers has an appeal to
      the area of drug delivery as it is comprised of polymers with a large number of
      derivatizable groups, a wide range of molecular weights, varying chemical
      compositions, and for the most part, a low toxicity and biodegradability, yet a
      high stability. The main scope of this review is to relate the polysaccharides
      available now to the rapidly growing field of colonic drug delivery.
      Polysaccharides have been applied to the area as controlled release coatings,
      matrices, macromolecular carriers, and biodegradable carriers. Bacterial sources
      of polysaccharidases as well as a detailed treatise of the enzymatic flora of the
      colonic region are discussed, followed by a presentation of the polysaccharides
      available for the purpose of colon-specific drug delivery. A final overview of
      the various approaches to obtain colon-specific delivery by using polysaccharides
      and a summary of available in vitro and in vivo testing methods will lead to the
      conclusion that polysaccharides at this point appear to be very promising
      compounds for use in obtaining colon-specific drug delivery systems.

PMID- 9016382
TI  - The role of scanning probe microscopy in drug delivery research.
AB  - The success of a drug delivery system is often dependent on the surface
      properties of the device. These surface properties will determine the complex
      dynamic interfacial events that occur when the system is introduced into the
      aqueous environment of a patient. Development of the scanning probe microscopes
      has provided a number of very powerful new surface analytical techniques that are
      making a significant contribution to the characterization of drug delivery
      systems and the interfacial processes that occur when such systems are exposed to
      aqueous living environments. In this review, we describe the design and
      attributes of these instruments and discuss the impact of the techniques on a
      wide range of drug delivery research. The scanning probe microscopes are
      providing new insights into important problems concerning drug delivery,
      including the molecular structure of polymeric biomaterial surfaces, the
      conformation of target biomolecules, the influence of morphology on
      biodegradation, the adsorption of proteins to synthetic surfaces, and the
      structure and interactions of colloidal particles. As the whole field of scanning
      probe microscopy continues to advance, drug delivery research is set to benefit;
      in the final section of the review, the future potential derived from the ability
      to characterize new surface properties under aqueous conditions is discussed.

PMID- 9016383
TI  - Transfersomes, liposomes and other lipid suspensions on the skin: permeation
      enhancement, vesicle penetration, and transdermal drug delivery.
AB  - Agents with MW < or = are being delivered transdermally with the aid of skin
      permeation enhancers that increase the agent's diffusivity and/or partitioning in
      the organ. Use of composite, lipidic agent-carriers (liposomes, niosomes) was not
      successful to date, due to the inability of such vehicles to pass through the
      narrow (< or = 30 nm) intercellular passages (virtual pores) in the outer skin
      layers. A solution to this problem are the orders of magnitude more deformable
      supramolecular aggregates, transfersomes. Such innovative drug-carriers are
      driven across the skin by the noturally occurring, concentration-insensitive, and
      probably hydration based, transepidermal gradient(s) and transport very efficient
      (> > 50%) and reproducibly various agents (200 < or = MW < or = 10(6);
      lipophilic/hydrophilic) into the body. Transfersomes were successfully used in
      animals and humans, also for the transcutaneous peptide and protein delivery. The
      theoretical rational for this is described together with the corresponding
      experimental models and practical examples.

PMID- 9016384
TI  - A plasma protein isolated from brown shrimp (Penaeus californiensis) which
      enhances the activation of prophenoloxidase system by beta-1,3-glucan.
AB  - A beta-glucan-binding protein (BGBP) has been identified in brown shrimp plasma
      by using a polyclonal antiserum against a BGBP from the freshwater crayfish. The
      protein was purified by immunoaffinity chromatography, and its molecular and
      biological properties described. Brown shrimp BGBP is a monomeric protein with a
      molecular mass of 100 kDa, similar to those described for other crustacean BGBPs.
      This protein is capable of enhancing the prophenoloxidase (proPO) system
      activation induced by laminarin. Both amino acid composition and N-terminal
      sequence are markedly similar to those of crayfish BGBP.

PMID- 9016385
TI  - Signal transduction during exocytosis in Limulus polyphemus granulocytes.
AB  - Bacterial lipopolysaccharide (LPS)-induced exocytosis is one of the primary
      immune responses of the Limulus granulocyte (GR). Exocytosis can be mediated by
      guanine nucleotide-binding protein (G-protein)-linked surface receptors that
      activate phospholipase C (PLC) to produce inositol 1,4,5-triphosphate (IP3) and
      diacylglycerol (DAG). IP3 mobilizes intracellular Ca2+ ([Ca2+]i), which can lead
      to exocytosis. We used activators and inhibitors of known signal transduction
      pathways to investigate the signaling pathway responsible for LPS-induced
      exocytosis in the GR. These compounds have been shown to similarly effect
      pathways in vertebrate and invertebrate systems and this assumption is made here.
      Pretreatment of GRs with cholera and pertussis toxins, which modulate G-proteins,
      and U73122, which inhibits PLC, inhibited LPS-induced exocytosis, but
      pretreatment with the tyrosine kinase inhibitor herbimycin did not. In contrast,
      exocytosis was induced with fluoride (a G-protein activator) and thapsigargin
      with Mg2+ (an inhibitor of endomembranous Ca(2+)-ATPase). Exocytosis was not
      induced by phorbol ester, which mimics DAG to activate protein kinase C (PKC) and
      it was not effected by ethanol or chelerythrine, which inhibit phospholipase D
      and PKC, respectively. Microinjection of GRs with different concentrations of
      IP3, an IP3 analog (DL-2,3,6,trideoxy-myo-inositol 1,4,5-triphosphate), Mg2+, or
      Ca2+ induced different percentages of exocytosis in individual cells, while HEPES
      buffer did not. Microfluorometric analysis of intracellular Mg2+ ([Mg2+]i) and
      [Ca2+]i, using the dyes Mag Fura-2AM and Calcium Green 5N, respectively, revealed
      [Mg2+]i and [Ca2+]i fluxes during LPS-induced exocytosis. This study suggests
      that LPS induces exocytosis in the Limulus GR through activation of G-protein
      coupled receptors, which stimulate the IP3 signaling pathway to induce both
      [Ca2+]i and [Mg2+]i fluxes to facilitate vesicular and plasma membrane fusion.
      This is the first demonstration of the signal transduction pathway responsible
      for the primary immune response of the GR.

PMID- 9016386
TI  - Kinetics of oxygen metabolism during respiratory burst in Japanese eel
      neutrophils.
AB  - Two oxygen radicals, superoxide and hydrogen peroxide, were measured by
      ferricytochrome C reduction and scopoletin fluorescent assays to investigate
      oxygen metabolism during the respiratory burst in Japanese eel neutrophils.
      Maximal superoxide production was obtained using 0.1 microgram/mL of PMA. Oxygen
      consumption was almost equivalent to superoxide production, indicating that the
      consumed oxygen was almost fully converted to superoxide in eel neutrophils.
      Hydrogen peroxide production was approximately half that of oxygen consumption or
      superoxide production in neutrophils elicited by killed bacteria or casein. The
      amounts of superoxide and hydrogen peroxide production, by neutrophils elicited
      by irritants, were about 11.5 and 5.0 nM/10(7) cells/ min, respectively, which
      were significantly higher than those of unelicited neutrophils (2.4 and 0.3
      nM/10(7) cells/min, respectively).

PMID- 9016387
TI  - Effects and mechanisms of environmental temperature on carp (Cyprinus carpio)
      anti-DNP antibody response and non-specific cytotoxic cell activity: a kinetic
      study.
AB  - The effect of environmental temperatures on immune competence was investigated in
      carp which were subjected to changes in water temperature. The activity of non
      specific cytotoxic cells (NCC) against P815 target cells, and the anti-DNP
      antibody response were evaluated until day 56 after transfer. Low environmental
      temperature (12 +/- 0.5 degrees C) enhanced NCC activity and decreased antibody
      production. In contrast a high environmental temperature (28 +/- 0.5 degrees C)
      was without effect on these parameters when compared to the standard temperature
      (20 +/- 0.5 degrees C). The results showed a maximum effect of low environmental
      temperature on day 28 and an adaptation in these immune responses 56 days
      following transfer. Collectively, the results indicated that non-specific
      immunity tends to offset specific immune suppression at low environmental
      temperatures. To determine the mechanism(s) by which environmental temperature
      affects cellular immune function, membrane fluidity measurements and sialic acid
      titration, as well as stress assessment by plasma cortisol measurement, were
      determined on day 28. Taken together, the results revealed a direct effect of
      temperature on cellular immune function which is modulated by membrane fluidity
      and sugar concentration and not by stress induction.

PMID- 9016388
TI  - Membrane immunoglobulin-associated molecules on channel catfish B lymphocytes.
AB  - Membrane immunoglobulin (mIgM) on the surface of channel catfish B lymphocytes is
      non-covalently associated with 64 and 70 kDa molecules which are composed of
      covalent 32 kDa dimers and covalent 45/25 kDa subunits, respectively. Cross
      linking of mIgM on catfish B cells leads to rapid phosphorylation of tyrosine
      residues in these presumed accessory as well as numerous other cytoplasmic
      molecules. These data indicate that fish likely use a signal transduction system
      containing elements similar to those of mammalian B cells.

PMID- 9016389
TI  - Age-dependent changes in peripheral blood lymphocyte subpopulations in cattle: a
      longitudinal study.
AB  - Immunofluorescence and flow cytometric analyses were used to study the age
      dependent changes in the peripheral blood lymphocyte (PBL) subpopulations in
      cattle. Four healthy Holstein heifer calves (A, B, C and D), 1-2 months of age,
      were used in this study. Sequential peripheral blood samples were collected once
      a month for up to 2-2.5 years, and once at approximately 4 years of age. For the
      first 6 months of age, the calves had similar proportions of CD2+, CD4+, CD8+ T
      lymphocytes, CD20+ B lymphocytes and MHC class II+ lymphocytes. From 2 months of
      age up to 2-2.5 years of age, all animals had similar proportions of CD5+ cells;
      but during the same period, animals A and B had significantly lower proportions
      of WC1+ gamma delta T cells than animals C and D. After 7 months of age, however,
      the proportions of CD2+, CD4+ and CD8+ T cells in PBL of animals A and B
      significantly decreased, whereas the proportions of both CD20+ B lymphocytes and
      MHC class II+ lymphocytes significantly increased. In contrast, the proportions
      of the various PBL subpopulations in animals C and D remained virtually unchanged
      after 7 months of age. For the first 6 months of age, all the calves showed
      similar absolute counts of PBL. Thereafter, the absolute counts of PBL in animals
      A and B significantly increased, but remained virtually unchanged in animals C
      and D. Throughout the study, from 1-2 months up to 2-2.5 years of age the
      absolute counts of CD2+, CD4+, CD8+ and WC1+ gamma delta T cells in PBL of the
      four animals were not significantly different from each other. Up to 6 months of
      age, the CD4+/ CD8+ ratio in all calves was 2.38 +/- 0.46, but significantly
      decreased thereafter to 1.81 +/- 0.34. However, there were no significant
      differences in the CD4+/CD8+ ratios among individual animals. The increase in the
      absolute counts of PBL in animals A and B, after 7 months of age, was due to an
      increase in the absolute counts of CD5+ cells, CD20+ B lymphocytes and MHC class
      II+ lymphocytes. Thus, changes in the percent, but not the absolute counts of T
      lymphocytes, were due to high percent and absolute counts of B lymphocytes,
      expressing the CD5 and MHC class II antigens.

PMID- 9016390
TI  - Ultrastructural observations of spermatogenesis in mice resulting from
      transplantation of mouse spermatogonia.
AB  - The objective of the present study was to provide a morphological
      characterization of spermatogenesis following germ cell transplantation into the
      seminiferous tubular lumen of another mouse. The recipient mice (W-locus) were
      sterile because of a defect in spermatogenesis resulting from the failure of
      virtually all germ cell precursors to migrate to the genital ridge during
      embryonic development. Recipient mice containing intratubular injections of
      testis cell suspensions from C57 mice were allowed to develop for over 1 year,
      whereupon animals were sacrificed and testis tissue examined by light and
      electron microscopy. Donor mouse cells formed normal cell associations (stages)
      as viewed in cross-sectioned tubules. Spermatogonia were found exclusively in the
      basal compartment, indicating that they were translocated from the tubule lumen
      through the Sertoli cell junctions, eventually to reside on the basal lamina.
      Some tubules looked entirely normal from both a quantitative and qualitative
      standpoint. Others showed qualitative and quantitative impairment. In some
      tubules a generation of cells was missing from a cell association. A variety of
      degenerating cells and structural abnormalities were responsible for this
      impairment, however, the most common abnormalities were seen during the
      elongation phase of spermatogenesis. Elongation abnormalities and the subsequent
      degeneration of these cells led to the presence of fewer-than-expected elongate
      spermatids. There were regions of the testis where no spermatogenesis was noted
      and only Sertoli cells were present. These regions were generally typical of the
      testis histology seen in animals not exposed to injected germ cells. However,
      Sertoli cells in these regions phagocytosed sperm produced in spermatogenically
      active regions of the tubules. Because transplantation of germ cells, either from
      fresh or from frozen cells, had wide-ranging implications in biology and
      medicine, characterization of spermatogonial transplants is an important step in
      improving this procedure.

PMID- 9016391
TI  - Ultrastructural observations of spermatogenesis following transplantation of rat
      testis cells into mouse seminiferous tubules.
AB  - The testes of busulfan-treated immunodeficient mice receiving seminiferous tubule
      injections of testis cells from rats were examined by light and electron
      microscopy. The presence of active rat spermatogenesis was verified by criteria
      that are known to characterize spermatogenic cells of this species. In addition,
      spermatogenesis from the mouse was identified as taking place in some
      seminiferous tubules as the result of reinitiation of spermatogenesis after
      busulfan treatment. Rat spermatogenesis in mouse seminiferous tubules showed the
      generally recognized associations of cells known to characterize stages of
      spermatogenesis of the rat. The Sertoli cells associated with rat spermatogenesis
      were identified ultrastructurally as being of mouse origin. Thus, rat
      spermatogenesis, which has a cycle length that is 50% longer than mouse
      spermatogenesis, can proceed among mouse Sertoli cells, which supposedly exert
      much shorter cyclic influences in concert with mouse germ cell development.
      Studies are needed to determine if the timing of rat spermatogenesis is
      controlled by the germ cells or the Sertoli cells. These observations are
      considered preliminary since a thorough study of somatic-germ cell relationships
      was not undertaken. It is concluded that a mouse Sertoli cell in the environment
      provided by the mouse testis can produce both mouse and rat gametes.

PMID- 9016392
TI  - Transcriptional regulatory strategies in male germ cells.

PMID- 9016393
TI  - Androgens and penile erection: a review.

PMID- 9016394
TI  - Pituitary control of proliferation and differentiation of Leydig cells and their
      putative precursors in immature hypophysectomized rat testis.
AB  - The objective of this study was to determine the effects of pituitary hormones
      (luteinizing hormone [LH], follicle-stimulating hormone [FSH], growth hormone
      [GH], and prolactin [PRL]) on interstitial cell proliferation and differentiation
      in the testis of immature hypophysectomized rats. Macrophages, Leydig cells,
      precursor mesenchymal cells, endothelial lymphatic cells, and myoid cells were
      studied. Our experimental approach was aimed at determining whether changes in a
      cellular subpopulation observed after pituitary hormone treatments were the
      result of division of existing cells in the population, of differentiation of
      interstitial precursor cells, or both. In this context, it must be stressed that
      our data reflected the effects of hormones to prevent the decline of cells due to
      hypophysectomy rather than their recovery. Macrophage proliferation was taken
      into account because macrophages closely resemble Leydig cells and are known to
      proliferate after hormonal treatment. A double-labeling procedure (acid
      phosphatase and anti-bromodeoxyuridine [anti-BUdR]) revealed that LH, FSH, and
      PRL increased the number of testicular macrophages 105-, 104-, and 103-fold,
      respectively, in hypophysectomized rats compared to hypophysectomized control
      animals. BUdR incorporation in testicular macrophages was greater after PRL
      treatment than after LH and FSH supplementation. In contrast, we were unable to
      demonstrate any effect of rat GH on the macrophage population. Light microscopic
      analysis of plastic embedded sections of treated rat testis revealed that LH
      increased the numbers of Leydig, precursor mesenchymal, and myoid cells 6-, 4-,
      and 1.3-fold, respectively. LH also stimulated BUdR incorporation into all
      interstitial cell types. PRL administration increased both the number of Leydig
      and precursor mesenchymal cells (each 3-fold) but decreased the number of
      endothelial lymphatic cells (1.5-fold) when compared to the control animals. In
      contrast, FSH did not increase the number and proliferation of Leydig cells but
      exerted a slight proliferative effect on the other interstitial cell populations.
      In GH-treated rats, the number of precursor mesenchymal cells increased two fold
      above the control rats. GH also exerted slight proliferative effects on both
      precursor mesenchymal and myoid cells. Immunohistochemical studies of
      steroidogenic enzymes in the testicular interstitium of treated rats demonstrated
      the presence of steroidogenic enzymes, not only in Leydig and precursor
      mesenchymal cells, but also in some (1%-2%) endothelial lymphatic cells and myoid
      cells. This may indicate that both of these cell types are also constitutively
      equipped to perform steroidogenesis or that they are precursor cells undergoing
      differentiation. Taken together, changes in the number of Leydig cells in our
      animal model appeared more likely to be dependent on the transformation of
      precursor cells than on division of preexisting mature Leydig cells.

PMID- 9016395
TI  - P450 aromatase messenger ribonucleic acid expression in male rat germ cells:
      detection by reverse transcription-polymerase chain reaction amplification.
AB  - We have previously demonstrated that cytochrome P450 aromatase (P450arom)
      protein, an estrogen-synthesizing enzyme, is present and active in germ cells of
      the adult mouse testis. To establish that P450arom mRNA is expressed in germ
      cells of other species, we examined expression of P450arom in adult rat germ
      cells by employing reverse transcription-polymerase chain reaction (RT-PCR).
      Total RNA was extracted from Staput separated germ cells and reverse transcribed.
      The resulting cDNA was amplified by nested PCR reactions using oligonucleotide
      primers selected from a highly conserved region of the P450arom gene. RT-PCR
      analysis yielded cDNA products of 334 bp in length that corresponded to the
      predicted size expected from the final nested amplification. The identity of the
      germ cell P450arom PCR products was confirmed by restriction enzyme analysis and
      direct nucleotide sequencing. Rat genomic DNA was subjected to PCR to verify that
      P450arom DNA products were not obtained from genomic DNA contamination. Rat
      genomic DNA yielded a nested PCR product for P450arom of approximately 2000 bp,
      suggesting that, as is the case with the human P450arom gene, the rat P450arom
      gene contains an intron in the amplified region. In addition, a semiquantitative
      technique was utilized to eliminate the possibility that the P450arom RT-PCR
      products were derived from Leydig cell contamination of Sta-put-separated germ
      cell preparations. RT-PCR for P450arom and 3-beta-hydroxysteroid dehydrogenase (3
      beta-HSD), a Leydig cell-specific steroidogenic enzyme, was carried out on Sta
      put-separated germ cells and interstitial cell preparations containing Leydig
      cells. P450arom and 3 beta-HSD RT-PCR reactions were stopped at three cycle
      intervals to detect and compare the earliest appearance of RT-PCR reaction
      products in various cell types. Results indicated that P450arom mRNA is detected
      in round spermatids before it is detected in interstitial cells, whereas 3 beta
      HSD was detected only in interstitial cells, suggesting that the P450arom mRNA
      detected in germ cells is not due to interstitial cell contamination of germ cell
      preparations. Therefore, our results indicate that P450arom mRNA is expressed in
      adult rat germ cells and that testicular germ cells are a potential source of
      estrogen in the male reproductive tract.

PMID- 9016396
TI  - Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal
      vesicle proteins after ejaculation.
AB  - We have recently demonstrated in liquefied human seminal plasma the presence of
      the novel kallikrein hK2 in association with protein C inhibitor (PCI) as a 75
      kDa complex. In the present study, we showed that hK2, immediately after
      ejaculation, was recovered only in its free form but complex formation with PCI
      occurred rapidly thereafter and was completed within 10 minutes. That reaction
      required an enzymatically active kallikrein. In order to determine the patterns
      of hydrolysis of major seminal vesicle proteins, semenogelins and fibronectin
      were exposed to hK2 and to hK3 (prostate-specific antigen or PSA) and cleavage
      sequences were identified by N-terminal sequencing. Free hK2 was able to
      hydrolyze semenogelins and fibronectin in vitro. Most of cleavage sites were at
      the carboxyl-side of arginyl residues. Semenogelins were hydrolyzed to a similar
      extent by catalytic (and similar) concentration of either hK2 or PSA though no
      common cleavage sites was identified for both proteinases. Unlike semenogelins,
      fibronectin was hydrolyzed much more efficiently by hK2 than by PSA. These
      results show that hK2 is enzymatically active during a short period of time after
      ejaculation, that major seminal vesicle proteins can be the target of this
      proteolytic activity, and that hK2 and PSA have different substrate
      specificities.

PMID- 9016397
TI  - Molecular characterizations of an intraacrosomal antigen defined by HS-33
      monoclonal antibody.
AB  - Among the numerous anti-sperm monoclonal antibodies generated in our laboratory,
      HS-33 was shown to react with a conserved antigen on the acrosome of spermatozoa
      from human and mouse. By using indirect immunofluorescent assay, it was
      demonstrated that HS-33 did not bind to live human sperm. However, this antibody
      was found to react with the methanol-fixed acrosome-intact, but not with acrosome
      reacted sperm. The human sperm antigen recognized by this antibody was purified
      from human sperm extract by immunoaffinity chromatography. The purified cognate
      human sperm antigen designated as HSAg-33 was found to be a protein with a
      molecular weight of approximately 72 kDa on sodium dodecyl sulfate polyacrylamide
      gel electrophoresis under reducing conditions. The tissue-specificity and the
      developmental expression of this sperm antigen were examined using frozen
      sections of various human and mouse tissues. The antigen was shown to be
      expressed specifically in the testicular sperm at the postmeiotic stages of
      spermatogenesis but not in any other somatic tissues. "Spontaneous" acrosome
      reaction was determined following 18 hours of incubation in Biggers, Whitten, and
      Whittingham (BWW) medium by using HS-33 monoclonal antibody and Pisum sativum
      agglutinin (PSA) as probes. The number of sperm stained positively with this
      antibody decreased significantly following overnight incubation, indicating the
      occurrence of an acrosome reaction. The results of this study suggest that HSAg
      33 is a potentially useful sperm-specific acrosome marker for studies of sperm
      capacitation and acrosome reaction.

PMID- 9016398
TI  - Use of peanut agglutinin to assess the acrosomal status and the zona pellucida
      induced acrosome reaction in stallion spermatozoa.
AB  - Peanut agglutinin (PNA) was used to assess the sperm acrosomal status and the
      acrosome reaction during gamete interaction in the equine species. PNA
      exclusively binds to the outer acrosomal membrane of stallion spermatozoa, as was
      established by transmission electron microscopy. Fluorescein isothiocyanate-PNA
      (FITC-PNA) labeling was used to monitor sperm acrosomal changes during a
      prolonged incubation period of 24 hours and during a 2-hours incubation in the
      presence of 5 microM calcium ionophore A23187. In addition, after a 4-hours
      preincubation in SP-TALP medium, sperm samples were incubated with matching
      hemizonae for 1 minute (onset binding) followed by a 60-minute incubation (1-hour
      binding) of the sperm-hemizona complexes in sperm-free medium to assess the
      acrosomal status of the bound spermatozoa. For acrosome assessment, spermatozoa
      and washed sperm-hemizona complexes were air dried onto microscope slides, fixed,
      permeabilized in ethanol, stained with FITC-PNA, and counterstained with the DNA
      dye ethidium homodimer. Both zona-bound and non-bound spermatozoa showed similar
      staining patterns. Acrosome-intact spermatozoa displayed intensively green
      fluorescence over the acrosomal cap, whereas reacting spermatozoa showed a patchy
      disrupted image of fluorescence. Sperm cells that completed the acrosome reaction
      were principally stained on the equatorial segment or not stained at all. During
      prolonged incubation and during the calcium ionophore treatment, the proportion
      of spermatozoa with an acrosomal modification (reacting) and a complete breakdown
      of the acrosome (reacted) increased noticeably. Significant induction of the
      acrosome reaction was observed within 60 minutes of sperm-zona contact (P <
      0.001). In conclusion, a rapid and reliable assessment of the acrosomal status
      and the incidence of the acrosome reaction of stallion spermatozoa at the zona
      surface were demonstrated in this study.

PMID- 9016400
TI  - Analysis of the effect of nitric oxide synthase inhibition on mouse sperm
      employing a modified staining method for assessment of the acrosome reaction.
AB  - A commercially available staining kit (Spermac) was combined with swelling in a
      hypoosmotic medium (HOS) for simultaneous assessment of viability and acrosome
      reaction in mouse spermatozoa. We compared the results obtained with the combined
      technique (HOS-Spermac) with those obtained with currently used techniques: the
      chlortetracycline fluorescence assay and eosin exclusion. The results obtained
      with HOS-Spermac were the same as those obtained with the chlortetracycline
      fluorescence assay. Viability assessment with HOS-Spermac showed a good
      correlation with the percentage of spermatozoa showing eosin dye exclusion. Using
      this novel technique, we studied the effect of a nitric oxide synthase inhibitor
      (NG-nitro-L-arginine methyl ester, L-NAME) on the acrosome reaction. L-NAME
      produced a dose-dependent inhibition of spontaneous acrosome reaction and its
      inhibitory effect was specifically counteracted by L-arginine. We conclude that
      HOS-Spermac provides a simple and reliable tool for assessment of the acrosome
      reaction and that nitric oxide synthase participates in this important function
      of the spermatozoon.

PMID- 9016399
TI  - Polyamine levels in testes and seminal vesicles from adult golden hamsters during
      gonadal regression-recrudescence.
AB  - The exposure of golden hamsters to short days results in early regression of the
      reproductive organs and subsequent spontaneous recrudescence characterized by
      active cellular regeneration and differentiation. Thus, adult male hamsters were
      subjected to short photoperiod (SP, 6L:18D) for 9, 12, 14, 16, 18, and 22 weeks
      or maintained under long photoperiod (LP, 14L:10D) for 22 weeks, to assess
      photoperiodic-related changes in testicular and seminal vesicle (SV) levels of
      polyamines (PA) that are involved in cell growth and differentiation. During the
      regression phase, the weights of the organs and the circulating levels of
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin,
      testosterone, dihydrotestosterone, and 5 alpha-androstane-3 alpha, 17 beta-diol
      were significantly diminished and, thereafter, during the recrudescence phase,
      they recovered total or partially their control values. In both tissues, the
      exposure to SP for 14-16 weeks resulted in an increase of PA concentrations,
      followed by a return to control levels in the recrudescence period. At the time
      of maximal tissue involution, the ornithine decarboxylase (ODC) activity (key
      regulatory enzyme of PA biosynthesis) showed a significant increase in testis,
      preceding the sharp peak of PA concentration. However, a marked decrease in ODC
      activity was detected in SV. The concentration of N-acetyl PA in SV showed an
      increment at 16 weeks of SP, while no modifications were detected in testicular
      concentration. When PA, N-acetyl PA, and ODC activity were expressed per testis
      and per SV, values fell significantly during the involution period, but in the
      recrudescence phase levels were recovered concomitantly with the restoration of
      the organ weight and function. In conclusion, the photoperiodic-related changes
      in PA and their N-acetyl derivatives might play a crucial role in regrowth and
      differentiation of the male sexual organs during the spontaneous recrudescence
      phase. Additionally, organ-specific regulation of the PA biosynthesis pathway
      could also take place.

PMID- 9016401
TI  - The relation between reactive oxygen species and cytokines in andrological
      patients with or without male accessory gland infection.
AB  - The presence of various cytokines, namely hepatocyte growth factor (HGF),
      interleukin-1 receptor antagonist (IL-1 RA), and interleukins (IL-1 alpha, IL-6,
      and IL-8), as well as the production of reactive oxygen species (ROS) was
      investigated in seminal plasma of fertile and infertile patients in order to
      evaluate the possible value of measuring these substances for the diagnosis of
      male accessory gland infection, and to assess the possible relationship between
      oxidative stress and cytokines during leucocytospermia and male accessory gland
      infection (MAGI). Our findings indicate that all of the measured cytokines seem
      to be produced locally as well as by white blood cells (WBC) and that, due to the
      presence of higher numbers of WBC, accessory gland infection may exert a
      deleterious effect on sperm quality through the production of ROS and/or of
      particular cytokines such as IL-1 alpha, IL-1 RA, and IL-8. The most specific
      marker for a sensitivity of 95% in discriminating between cases with or without
      MAGI is the measurement of IL-6 in seminal plasma. In the absence of WBC several
      cytokines are constitutively produced and correlate with sperm concentration
      (HGF, IL-8), alpha-glucosidase (IL-6), and gamma-glutamyltransferase activity
      (HGF). The measurement of these cytokines in semen may provide clinically useful
      information for the diagnosis of male accessory gland infection, as well as in
      the absence of WBC where it can provide information about certain mechanisms of
      male reproductive function and dysfunction.

PMID- 9016402
TI  - Isolation of highly purified type A spermatogonia from prepubertal rat testis.
AB  - We have developed a new method that allows isolation of highly purified type A
      spermatogonia from prepubertal rats. The procedure is based on the maximal
      release of spermatogonia from the seminiferous epithelium obtained by the
      complete enzymatic digestion of the tubular basal lamina, followed by removal of
      contaminating somatic cells through adhesion to plastic dishes coated with the
      lectin Datura stramonium agglutinin and fractionation on a discontinuous Percoll
      gradient. The cell suspension obtained contains up to 85% type A spermatogonia.
      Besides morphological criteria, the identification of germ cells and somatic
      cells has been performed by means of immunocytochemical markers, such as c-kit
      receptor, which is present only in germ cells, and vimentin, which is present
      only in somatic cells. All type A spermatogonia isolated were c-kit positive,
      thus suggesting that c-kit receptor is present in both undifferentiated and
      differentiating type A spermatogonia. Preliminary culture experiments demonstrate
      that spermatogonia survival in vitro was significantly improved by the addition
      of 10% fetal calf serum or horse serum to the culture medium; however, optimal
      culture conditions remain to be established. In vitro studies on isolated
      spermatogonia may provide a significant contribution toward elucidation of the
      mechanisms regulating spermatogonial proliferation and differentiation.

PMID- 9016403
TI  - The influence of semen analysis parameters on the fertility potential of
      infertile couples.
AB  - The objective of this study was to investigate the relationship between couples'
      fertility potential and several parameters of semen analysis (from a single semen
      sample/male partner) in a cohort of 1,055 infertile couples seen at the Texas
      Institute for Reproductive Medicine and Endocrinology for a total of 9,409 follow
      up months. The medians of sperm concentrations (SC), total sperm counts (TSC),
      percent motility (MOT), motile sperm concentrations (MSC), and total motile sperm
      counts (TMSC) were significantly higher (P < 0.0001) in the group that achieved
      pregnancy. When the entire group was divided into "high" and "low" groups on the
      basis of the various parameters of semen analysis, the relative risk ratios for
      conception for the "high" groups were as follows: SC, 1.5; MOT, 8.5; TSC, 8.1;
      MSC, 5.8; and TMSC, 6.1. Life table analysis showed a statistically significant
      difference (P < 0.0001) in the initial rise and overall slope of the conception
      rates between the two groups for a number of the semen analysis parameters (TSC,
      MOT, MSC, and TMSC). This study showed that certain semen analysis parameters are
      positively correlated, with a high degree of statistical probability, with the
      time required for the occurrence of conception. The quantitative impact of the
      male fertility potential on conception rates was shown to correlate not solely
      with the SC or MOT values, but even more so with their derivatives (i.e., MSC and
      TMSC). Therefore, in an in vivo environment it is not only the number of sperm
      and their motility but also their derivatives that provide a quantitative insight
      into the male fertility potential. The data may provide a quantitative expression
      of the relative risk ratio for conception to occur and the time required until
      conception is achieved. Further studies will be necessary to clarify the effect
      of the other semen analysis parameters (i.e., morphology, velocity, linearity,
      and "efficient" MSC) on conception rates, cumulative conception rates, relative
      risk ratio for conception, and time until conception in a large population of
      infertile couples.

PMID- 9016404
TI  - Prevention of seminiferous tubular atrophy in a naturally cryptorchid rat model
      by early surgical intervention.
AB  - In an attempt to determine whether the seminiferous tubular atrophy of the
      cryptorchid testis is preventable by early surgical correction of the cryptorchid
      state, aberrantly developed gubernacula destined to result in a cryptorchid
      testis in the Long-Evans cryptorchid (LE/ORL) rat were surgically reimplanted to
      the bottom of the scrotum on day 10 to 12 of age. Testis descent was monitored
      and the changes in testicular histology and in the volumes of the seminiferous
      tubules and Leydig cells were examined at day 60. As expected, normal testis
      descent occurred on or about day 25. Compared to untreated undescended testes at
      day 60, relative seminiferous tubular volumes (volume: % +/- SEM) were
      significantly increased by early surgical reimplantation of the gubemacula (89 +/
      1 vs. 66 +/- 3; P < 0.01). Absolute seminiferous tubular volumes (microliter +/-
      SEM) were also significantly increased by early surgical intervention when
      compared to undescended nontreated testes (893 +/- 27 vs. 170 +/- 12; P < 0.01).
      The testes of the surgically corrected cryptorchid animals were similar in all
      respects to those found in the descended testes of the sham-operated controls.
      Relative Leydig cell volume (% +/- SEM) was increased in the untreated
      cryptorchid testes compared to the surgically corrected testes (5.2 +/- 0.6 vs.
      1.2 +/- 1.0; P < 0.05). Relative Leydig cell volumes in the surgically corrected
      testes were not significantly different from those found in the sham-operated
      descended controls. A modest but significant (P < 0.05) increase in absolute
      Leydig cell volume was also noted in the cryptorchid testes when compared both to
      normal controls or surgically corrected cryptorchid testes. From these
      observations, we conclude that early gubernaculopexy reverses the histologic
      changes normally seen in the cryptorchid rat testis to a relatively normal
      histologic architecture. These data provide experimental evidence to support the
      value of orchiopexy in the treatment of cryptorchidism.

PMID- 9016406
TI  - Stabilization of helical peptides by mixed spaced salt bridges.
AB  - Whether or not surface salt bridges have a strong stabilizing effect on the
      native structure in proteins remains uncertain. Previous studies of model
      peptides have shown that salt bridges spaced at i,i +4 along the chain are more
      stabilizing than those spaced at i,i +3, with a preference for the order acid
      base rather than base-acid from N to C terminus. An analysis of the effect of
      spacing the ion pairs in short helical peptides is presented, in which acidic and
      basic side chains spaced two or three residues apart alternate along the chain.
      The mixed spacing proves to be stabilizing relative to pure spacings. A control
      peptide in which salt bridges were spaced uniformly three residues apart proved
      to form a beta-sheet structure rather than alpha-helix. This is due to formation
      of a silk-like apolar face consisting of alanine side chains; the mesoscopic
      structure formed by these sheets can be imaged by scanning microscopy.

PMID- 9016405
TI  - Reactivity of human deferential artery to constrictor and dilator substances.
AB  - The present study was designed to investigate general morphology and the response
      of human deferential artery to constrictor and dilator substances with special
      emphasis on endothelium-dependent responses. Human deferential artery segments
      were obtained from patients undergoing radical cystectomy (n = 7), suprapubic
      prostatectomy (n = 6), or radical prostatectomy (n = 6). Light microscopy
      revealed that human deferential artery is of muscular type, and fluorescence
      microscopy showed a dense adrenergic innervation. Paired rings, one normal and
      the other de-endothelialized by gentle rubbing, were mounted for isometric
      recording of tension in organ baths. Vasopressin, endothelin, serotonin, and
      potassium chloride induced endothelium-independent contractions, whereas
      norepinephrine and electrical field stimulation caused frequency-dependent
      contractions that were of greater magnitude in arteries denuded of endothelium.
      In precontracted arterial rings, acetylcholine and substance P induced
      endothelium-dependent relaxations. In contrast, papaverine and sodium
      nitroprusside caused concentration-dependent relaxations that were similar in the
      presence and in the absence of endothelium. NG-nitro-L-arginine methyl ester (10(
      4) M), an inhibitor of nitric oxide synthase, potentiated the responses to
      norepinephrine in artery rings with endothelium, nearly abolished the
      acetylcholine-induced relaxation, and attenuated the relaxation induced by
      substance P. incubation with methylene blue (10(-5) M), an inhibitor of guanylate
      cyclase, completely prevented the relaxation induced by acetylcholine in arteries
      with endothelium. The results of this study indicate that the human deferential
      artery has a dense adrenergic innervation and marked ability to contract or relax
      in response to different agonists. Some of these responses are in part
      endothelium dependent and mediated through release of nitric oxide. These
      morphological and pharmacological observations could play an important role in
      regulating flow or pressure of blood that arrives to the vas deferens.

PMID- 9016407
TI  - Molecular modelling study of the netropsin complexation with a nucleic acid
      triple helix.
AB  - A detailed molecular mechanical study has been made on the complexes of netropsin
      with the double stranded oligonucleotide (dA)12.(dT)12 and with the triple helix
      (dA)12.(dT)12.(dT)12. The complexes were built using computer graphics and energy
      refined using JUMNA program. In agreement with circular dichroism experiments we
      have shown that 3 netropsins can bind the minor grooves of the triple helix and
      of the double helix. The groove geometry in the duplex and in the triplex is very
      similar. However a detailed analysis of the energetic terms shows, in agreement
      with thermal denaturation studies, that the affinity of netropsin toward the
      double helices is larger than towards triple helices.

PMID- 9016408
TI  - Molecular dynamics simulation of conformational flexibility of alamethicin
      fragments in aqueous and membranous environment.
AB  - We present here results on molecular dynamics (MD) simulation on two fragments of
      channel forming antibiotic peptide Alamethicin, containing isoamino butyric acid
      (Aib). Simulations are carried out in aqueous and membranous environment in a
      bilayer of 39 molecules of Dimyristoyl phosphatidyl choline (DMPC). The peptides
      Boc-Pro-Aib-Ala-Aib-OBzl (Alam 1) and Boc-Leu-Aib-Pro-OBzl (Alam 2) were
      simulated from their crystallographic coordinates. The bilayers were built from
      two different conformations (A and B) of DMPC reported in crystal data. The P-N
      dipoles were arranged hexagonally with surface area per lipid molecule 66.5 A
      degrees 2 and P-P separation across the bilayer 34 A degrees. They were hydrated
      by 28.6 and 25.5 water molecules per DMPC molecule. Simulations are done using
      AMBER 4.0 package in constant number volume temperature (NVT) condition for 100
      pico seconds (ps) in aqueous environment and 250 ps of equilibrated bilayer.
      Geometric parameters of lipids as: bilayer thickness, order parameter of the
      chains, transfraction of chain torsional angles were monitored. We also monitored
      geometric parameters of the peptides as backbone torsional angles, distances
      amongst C alpha atoms, angles between C alpha atoms, movement of center of
      gravity (CG) along and perpendicular to bilayer normal. We find that membrane
      bilayer is slightly disturbed due to the presence of peptides. In case of alam 2
      in water angles phi 1 and phi 3 showed larger variation in water compared to same
      in the bilayer. The peptide conformation is more stable in DMPC bilayer. However
      the peptides showed movement along and perpendicular to bilayer normal. This we
      believe is due to hydrophobic nature of these peptides.

PMID- 9016409
TI  - Different effects of nonintercalative antitumor drugs on DNA triple helix
      stability: SN-18071 promotes triple helix formation.
AB  - The interaction of the nonintercalating bisquaternary ammonium heterocyclic drugs
      SN-18071 and SN-6999 with a DNA triple helix has been studied using thermal
      denaturation and CD spectroscopy. Our data show, that both minor groove binders
      can bind to the triple helix of poly(dA).2poly(dT) under comparable ionic
      conditions, but they influence the stability of the triplex relative to the
      duplex structure of poly(dA).poly(dT) in a different manner. SN-18071, a ligand
      devoid of forming hydrogen bonds, can promote triplex formation and thermally
      stabilizes it up to 500 mM Na+ concentration. SN-6999 destabilizes the triplex to
      duplex equibilirium whereas it stabilizes the duplex. The binding constant of SN
      18071 is found to be greater than that to the duplex. The stabilizing effect of
      SN-18071 is explained by electrostatic interactions of three ligand molecules
      with the three grooves of the triple stranded structure. From the experiments it
      is concluded that SN-6999 binds to the triplex minor groove thereby destabilizing
      the triplex similar as previously reported for netropsin.

PMID- 9016410
TI  - Selective DNA binding of (N-alkylamine)-substituted naphthalene imides and
      diimides to G+C-rich DNA.
AB  - Alkylamine-substituted naphthalene imides and diimides bind DNA by intercalation
      and have applications as anticancer agents. The unique structures of these imides
      in which two adjacent carbonyl groups lie coplanar to an extended aromatic ring
      system allow the possibility of sequence-selective interactions between the
      intercalated chromophore and guanine amino groups situated in the DNA minor
      groove. The binding affinities of N-[3-(dimethylamino)propyl amine]-1,8
      naphthalenedicarboxylic imide (N-DMPrNI) and N,N'-bis [3,3'
      (dimethylamino)propylamine]-naphthalene-1,4,5,8-tetracarboxylic diimide (N
      BDMPrNDI) for natural DNAs of differing base composition were determined
      spectroscopically and by equilibrium dialysis. In agreement with the above
      proposition, binding studies indicated that both the naphthalene imide and
      diimide strongly prefer to intercalate into steps containing at least one G:C
      base pair. The dependencies of association constants on DNA base composition are
      consistent with a requirement for one G:C pair in the binding site of the
      monomide, and two G:C pairs in binding sites of the diimide. These selectivities
      are comparable to or exceed that of actinomycin D, a classic G:C-selective drug.
      Protection footprinting with DNase I confirmed that the naphthalene monoiimide (N
      DMPrNI) prefers to bind adjacent to G:C base pairs, with a most consistent
      preference for "mixed" steps containing both a G:C and an A:T pair, excepting
      GA:TC. Several 5'-CG-3' steps were also good binding sites as indicated by
      nuclease protection, but few GC:GC or GG:CC steps were protected. The naphthalene
      diimide inhibited DNase I digestion, but did not yield a footprint. The base
      recognition ability and versatile chemistry make naphthalene imides and diimides
      attractive building blocks for design of highly sequence-specific, DNA-directed
      drug candidates including conjugated oligonucleotides or oligopeptides.

PMID- 9016411
TI  - Optimization of cross-linked lexitropsins.
AB  - In attempts to optimize the cross-linked lexitropsin design, a number of cross
      linked dimers composed of two tris(N-methylpyrrolecarboxamide) strands were
      synthesized and their binding interactions with poly d(A).poly d(T) and poly d(A
      T).poly d(A-T) were characterized by circular dichroism and ethidium fluorometry.
      While all alkanediyl-linked dimers showed a similar binding behavior to the homo
      AT polymer, particularly at low ligand concentrations, the decanediyl linker was
      found to be the optimal linker permitting the bidentate antiparallel side-by-side
      binding of the corresponding dimer to the alternating AT polymer. Thus, in
      comparison with the monomer, the decanediyl-linked dimer has a binding strength
      enhancement of about 1400 times in the 1:1 binding mode. Moreover, the
      hydrophilicity of the linker dimer has a significant effect on the bidentate
      binding strength. The (3,6)-dioxaoctanediyl-linked dimer has a further binding
      strength enhancement of 10 times over the decanediyl-linked dimer. Overall, the
      best optimized dimer has a binding strength enhancement of over 14,000 times in
      comparison with the monomer in the 1:1 binding mode. This binding enhancement
      parallels that observed in the best optimized bisintercalators. Distance
      restrained molecular modeling provides support for the experimental results.
      Dimers of longer linkers can readily accommodate a bidentate antiparallel side-by
      side binding mode but those of shorter linkers necessitate marked structural
      distortions in the bound ligand molecules. It is further observed that the
      binding strength enhancement to the alternating AT polymer is not always
      accompanied by the binding specificity improvement. Our analysis suggests that
      the non-specific appendage-DNA backbone interaction is a key factor that controls
      the specificity improvement.

PMID- 9016412
TI  - DNA quadruplexes assembled by simple peptide: effects of DNA homology and peptide
      removal.
AB  - Formation of heterologous (calf thymus dsDNA) and homologous (linearized pBR322
      plasmid dsDNA) quadruplexes upon binding with the simple aliphatic tripeptide
      derivative (L-Val)3-N2H2-DNS.CF3COOH-DHTV) was examined by fluorimetry, flow
      linear (LD), circular dichroism (CD), and electron microscopy (EM). The
      morphology of the rod-like compact particles formed due to the association of
      dsDNA segments proved to be the same for both DNAs, whereas the stability of the
      compact DNA structure upon tripeptide removal from the complex with DNA differed
      substantially for homologous versus non-homologous dsDNA used. The increase in
      NaCl concentration in the solution up to 30 mM removes the peptide from both
      types of the complexes completely. At the same time at 20 mM NaCl calf thymus DNA
      quadruplexes readily dissociate, whereas the structures formed by plasmid DNA
      retain their morphology in the solution containing NaCl with concentrations up to
      40 mM and are only partially disrupted at even higher NaCl concentration. These
      results provide an analogy between trivaline-DNA model complexes and RecA-DNA
      binding.

PMID- 9016413
TI  - Fluorescence resonance energy transfer analysis of the degradation of an
      oligonucleotide protected by a very stable hairpin.
AB  - In vitro degradation of antisense oligonucleotides protected or not on their 3'
      side against enzymatic attack by a naturally forming hairpin has been studied by
      fluorescence resonance energy transfer (FRET). The two oligonucleotides
      d(5"TTCTCGCGAAGC3') forming the hairpin and d(5"TTCTCCGGAAGC3') as a control were
      labeled on their 5' side by tetramethylrhodamine and on their 3' side by
      fluorescein. Fluorescein has been shown not to hinder the hairpin formation and
      to give an additional protection against nucleases. The FRET technique proved
      adequate for an in situ study of these protected antisense oligonucleotides in
      living cells.

PMID- 9016414
TI  - Differential scanning calorimetric and X-ray study of the binding of the water of
      primary hydration to calf-thymus DNA.
AB  - Differential scanning calorimetry has been used to study the thermal properties
      of hydrated films of calf-thymus Na-, K- and CsDNA between 20 and 320 degrees C.
      A broad endothermic transition near 75 degrees C and a sharp exothermic
      transition near 240 degrees C are observed. The broad transition is due to the
      dehydration of the DNA, while the exothermic transition is due to pyrolysis of
      the sample. the peak temperatures of both transitions increase as the scan rate
      is increased. Based on a Kissinger analysis, the net activation energy for the
      desorption of the primary water of hydration is about 0.6 eV while that for the
      pyrolysis is about 1.9 eV. X-ray diffraction patterns suggest that heating the
      DNA films to 180 degrees C once does not, but thrice does, destroy their
      structural ordering.

PMID- 9016415
TI  - Induction of helical conformation in all beta-sheet proteins by trifluoroethanol.
AB  - The effect of 2,2,2-Trifluoroethanol (TFE) on the structure of five all beta
      sheet proteins, isolated from the venom of the Taiwan cobra (Naja naja atra), is
      studied. In all the toxins used, it is observed that significant amount of alpha
      helix is induced at higher concentrations of TFE. In all these proteins, the
      induction of helical conformation and disruption of the tertiary structure seem
      to occur simultaneously. The structural transitions induced by TFE in reduced and
      denatured protein appear to be different from those observed in the native
      protein(s). In our opinion, the findings reported herein could have significant
      implications on research in the area of protein folding.

PMID- 9016416
TI  - X-ray studies on crystalline complexes involving amino acids and peptides. XXXI.
      Effect of chirality on ionization state, stoichiometry and aggregation in the
      complexes of oxalic acid with L- and DL-histidine.
AB  - Crystals of the oxalic acid complex of L-histidine (orthorhombic P2(1)2(1)2(1); a
      = 5.535(4), b = 6.809(4), c = 26.878(3) A; R = 3.6% for 1188 observed
      reflections) contain histidine molecules and semi-oxalate ions in the 1:1 ratio,
      while the ratio is 1:2 in the crystals of the DL-histidine complex (monoclinic
      P2(1)lc; a = 6.750(7), b = 10.139(2), c = 19.352(2) A, beta = 90.8 degrees; R =
      3.7% for 3176 observed reflections). The histidine molecule in the latter has an
      unusual ionization state with positively charged amino and imidazole groups and a
      neutral carboxyl group. The molecule has the sterically least favourable allowed
      conformation with the side chain imidazole ring staggered between the alpha-amino
      and the alpha- carboxyl (carboxylate) groups, in both the structures. The unlike
      molecules aggregate into separate alternating layers in both of them. There are
      elements of similarity in the aggregation patterns in the semi-oxalate layers in
      the two complexes, but the patterns in the amino acid layers are entirely
      different. Interestingly, the crystal structure of L-histidine semi-oxalate has
      broad similarities with that of DL-histidine = glycolate, demonstrating how broad
      features of aggregation could be retained inspite of changes in chirality and
      composition. The unusual ionization state of the amino acid molecule in the DL
      histidine complex is reflected in a hitherto unobserved aggregation pattern in
      its crystal structure.

PMID- 9016417
TI  - Failure to prescribe warfarin to patients with nonrheumatic atrial fibrillation.
AB  - OBJECTIVE: To determine how often warfarin was prescribed to patients with
      nonrheumatic atrial fibrillation in our community in 1992 when randomized trials
      had demonstrated that warfarin could prevent stroke with little increase in the
      rate of hemorrhage, and to determine whether warfarin was prescribed less
      frequently to older patients-the patients at highest risk of stroke but of most
      concern to physicians in terms of the safety of warfarin. DESIGN: Cross-sectional
      study. Appropriateness of warfarin was classified for each patient based on the
      independent judgments of three physicians applying relevant evidence and
      guidelines. SETTING: Two teaching hospitals and five community-based practices.
      PATIENTS: Consecutive patients with nonrheumatic atrial fibrillation (n = 189).
      MEASUREMENTS AND MAIN RESULTS: Warfarin was prescribed to 44 (23%) of the 189
      patients. Warfarin was judged appropriate in 98 patients (52%), of whom 36 (37%)
      were prescribed warfarin. Warfarin was prescribed to 11 (14%) of 76 patients aged
      75 years or older with hypertension, diabetes mellitus, or past stroke, the group
      at highest risk of stroke. In a multivariable logistic regression model
      controlling for appropriateness of warfarin and other patient characteristics,
      patients aged 75 years or older were less likely than younger patients to be
      treated with warfarin (odds ratio 0.25; 95% confidence interval 0.10, 0.65).
      CONCLUSIONS: Warfarin was prescribed infrequently to these patients with
      nonrheumatic atrial fibrillation, especially the older patients and even the
      patients for whom warfarin was judged appropriate. These findings indicate a
      substantial opportunity to prevent stroke.

PMID- 9016419
TI  - Physician role conflict and resulting career changes. Gender and generational
      differences.
AB  - OBJECTIVE: To evaluate gender and generational differences both in the prevalence
      of role conflict and in resulting career changes among married physicians with
      children. STUDY DESIGN: Cross-sectional survey. PARTICIPANTS: We sent a survey to
      equal numbers of licensed male and female physicians (1,412 total) in a Southern
      California county; of the 964 delivered questionnaires, 656 (68%) were returned
      completed. Our sample includes 415 currently married physicians with children,
      64% male and 36% female. MEASUREMENTS AND MAIN RESULTS: The prevalence of
      perceived role conflict, or career changes for marriage, and of career changes
      for children were evaluated. Types of career changes were also evaluated. More
      female than male physicians (87% vs 62%, p < .001) and more younger than older
      female physicians (93% vs 80%, p < .01) and male physicians (79% vs 54%, p <
      .001) experienced at least moderate levels of role conflict. Younger female and
      male physicians did not differ in their rates of career change for marriage (57%
      vs 49%), but female physicians from both age cohorts were more likely than their
      male peers to have made career changes for their children (85% vs 35%, p < .001).
      Younger male physicians were twice as likely as their older peers to have made a
      career change for marriage (49% vs 28%, p < .001) or children (51% vs 25%, p <
      .001). The most common type of career change made for marriage or children was a
      decrease in work hours. CONCLUSIONS: Most physicians experience role conflict,
      and many adjust their careers in response. Flexible career options may enable
      physicians to combine professional and family roles more effectively.

PMID- 9016418
TI  - Why isn't warfarin prescribed to patients with nonrheumatic atrial fibrillation?
AB  - OBJECTIVE: To determine the opinions of selected physicians in our community
      about use of warfarin for patients with nonrheumatic atrial fibrillation, and to
      determine the relation of the physicians' opinions to their practices. DESIGN:
      Survey of physicians, using eight hypothetical clinical vignettes to characterize
      physicians' opinions about use of warfarin in patients with nonrheumatic atrial
      fibrillation, according to patient age, risk of bleeding, and risk of stroke.
      SETTING: Two teaching hospitals and five community-based practices. PARTICIPANTS:
      Eighty physicians who cared for 189 consecutive patients with nonrheumatic atrial
      fibrillation. MEASUREMENTS AND MAIN RESULTS: The survey response rate was 73%.
      Nearly all responding physicians (90%) recommended warfarin for at least one
      vignette. However, physicians recommended warfarin less often for vignettes
      depicting 85-year-old patients than for matched vignettes depicting 65-year-old
      patients (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.01, 0.08), and
      less often for cases with specified risk factors for bleeding than for matched
      cases without the risk factors (OR 0.01; 95% CI 0.004, 0.03); warfarin was
      recommended more often for cases with a recent stroke than for matched cases
      without this history (OR 8.2; 95% CI 3.6, 18). In practice, warfarin was
      prescribed more often (p < or = .05) by physicians reporting good personal
      experience and by those who had favorable opinions about its use. However, even
      physicians with good experience and favorable opinions did not prescribe warfarin
      to half of their patents for whom warfarin was independently judged appropriate.
      CONCLUSIONS: Physicians' opinions frequently opposed warfarin for older patients
      with nonrheumatic atrial fibrillation, and for those with bleeding risk factors.
      Physicians' opinions, as well as other barriers to warfarin therapy, most likely
      contribute to its infrequent prescription.

PMID- 9016420
TI  - Racial differences in the medical treatment of elderly Medicare patients with
      acute myocardial infarction.
AB  - OBJECTIVE: To compare the use of medications in African-American and Caucasian
      elderly Medicare patients hospitalized with acute myocardial infarction (AMI) in
      Alabama. DESIGN: Retrospective medical record review. SETTING: All acute care
      hospitals in Alabama. PATIENTS: All Medicare patients with a principal discharge
      diagnosis of AMI from June 1992 through February 1993. We excluded those patients
      less than 65 years of age and those of ethnicity other than African-American or
      Caucasian (N = 4,052). MEASUREMENTS: We first performed a crude analysis using
      all cases to compare by race the use of thrombolysis, beta-adrenergic blockade,
      and aspirin in the setting of AMI. In addition, we developed a multivariable
      model with receipt of therapy as the outcome and demographics, severity of
      illness, comorbidity, and algorithm-determined candidacy for therapy as
      covariates. The algorithms, developed as part of the Cooperative Cardiovascular
      Project, were designed to identify an "ideal" pool of candidates for each
      therapy. MAIN RESULTS: For all cases, 9.2% (95% confidence interval [CI] 6.8,
      12.1) of African Americans received thrombolysis compared with 17.3% (95% CI
      16.0, 18.6) of Caucasians. Approximately 16.4% of patients received beta
      adrenergic blockade, and 45.1% received aspirin, both with no racial difference.
      By multivariate analysis, the adjusted odds ratio for African Americans receiving
      thrombolysis was 0.55 (95% CI 0.41, 0.76). The corresponding odds ratio was 1.25
      (95% CI 0.99, 1.59) for beta-adrenergic blockade and 1.13 (95% CI 0.96, 1.37) for
      aspirin. African Americans presented later after the onset of chest pain, but the
      refusal rate of thrombolytic therapy did not differ. CONCLUSIONS: According to
      this analysis, Alabama physicians used beta-adrenergic blockade and aspirin
      equivalently in African Americans and Caucasians. African Americans received
      thrombolysis less often according to the crude analysis. The multivariable
      analysis suggests less use of thrombolytics, even after adjusting for several
      covariates including indication by clinical algorithm. However, the small number
      of African-American patients deemed ideal candidates for thrombolysis attenuates
      the precision of this finding.

PMID- 9016421
TI  - Does treatment with L-thyroxine influence health status in middle-aged and older
      adults with subclinical hypothyroidism?
AB  - OBJECTIVE: To determine if health-related quality of life (HRQL) in patients of
      middle age and older with elevated thyroid-stimulating hormone (TSH) and normal
      total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine
      replacement therapy. DESIGN: Randomized, double-blind, placebo-controlled trial.
      SETTING: Outpatient clinic. PATIENTS: Thirty-seven patients with subclinical
      hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years
      of age. INTERVENTIONS: Placebo or L-thyroxine replacement therapy to achieve
      normal TSH level. MEASUREMENTS AND MAIN RESULTS: Disease-specific and general
      HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose
      of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH
      decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4
      increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically
      significant improvement in a composite psychometric memory score in treated
      versus control patients; all other outcomes showed similar findings in the two
      groups. Although confidence intervals for most measures did not exclude an
      important improvement in HRQL with thyroid replacement, no measure of symptoms or
      HRQL either showed clinically important trends in favor of treatment, or
      approached conventional levels of statistical significance. CONCLUSIONS: In
      middle-aged and older patients with elevated TSH and normal T4, it may not be
      harmful to follow biochemical and clinical status even in the presence of
      nonspecific symptoms potentially associated with hypothyroidism.

PMID- 9016422
TI  - Incidence of three sexually transmitted diseases during a safer sex promotion
      program for HIV-infected women.
AB  - Promotion of safer sex practices typically includes education, skills building,
      and condom distribution. To evaluate the impact of such promotions and describe
      risk factors for sexually transmitted disease (STD), a retrospective review of
      741 sexually active HIV-infected women was conducted. The cohort was African
      American (82%), at least 22 years of age (81%), acquired HIV through sex (36%),
      had a CD4 count above 200/ mm3 (76%), and had a history of substance (alcohol or
      drug) use (38%). Those with incident STD (14.7%) were more likely to be under 22
      years of age, to have a history of substance use, and to have an STD at entry.
      Traditional methods of promoting safer sex practices should be enhanced by other
      options such as regular screening, partner treatment, and the use of microbicides
      and other female-controlled methods.

PMID- 9016423
TI  - Utility of a standardized sign-out card for new medical interns.
AB  - Conscientious sign-out between medical interns is important for the continuity of
      care of hospitalized patients. We developed a standardized sign-out card that
      prompted the intern going off duty to transmit patient care information to the
      inter on call. The card was tested in a prospective, randomized, controlled trial
      in which one group of interns used the card, and another group did not. Any
      instance of poor sign-out was reported on a questionnaire completed by the intern
      who had been on call the previous night. The group using the sign-out cards
      reported poor sign-out on 8 nights (5.8% of questionnaires), and the control
      group reported it on 17 nights (14.9% of questionnaires, p = .016). The card was
      time-effective and inexpensive, resulted in more complete data recording, and
      possibly decreased the morbidity associated with poor sign-out.

PMID- 9016424
TI  - Positive predictive value of clinical suspicion for abdominal aortic aneurysm.
      Implications for use of ultrasonography.
AB  - To measure the positive predictive value (PPV) of clinical suspicion of abdominal
      aortic aneurysm (AAA), as confirmed by ultrasonography, we reviewed the records
      of 343 patients at a university medical center referred to ultrasonography for
      newly suspected AAA. Positive predictive value was 11.1% for large aneurysms of
      at least 5.0 cm and 18.7% for aneurysms of at least 3.5 cm, and was higher for
      men and older patients. For patients under 50 years of age, PPV was only 2.6%.
      Ultrasonography for clinically suspected AAA has a low positive predictive yield,
      particularly for men under age 50 and for women.

PMID- 9016425
TI  - Sleep history is neglected diagnostic information. Challenges for primary care
      physicians.
AB  - Sleep problems are treatable causes of morbidity and mortality, but little is
      known about how often the history fundamental to diagnosis is obtained. We
      recorded the frequency of sleep histories during encounters with simulated
      patients by 20 experienced primary care practitioners, 23 uninstructed medical
      interns, and 22 interns who had previous instruction about sleep disorders. Sleep
      histories were uncommonly obtained by uninstructed physicians (0% of
      practitioners, 13% of interns), but trained interns more often (81.8%) asked
      about sleep. If sleep problems are to be prioritized, major changes in physician
      education and behaviors are essential. Focused instruction about sleep influences
      physician behavior.

PMID- 9016426
TI  - Risk factors for nonelective hospital readmissions.
AB  - We previously reported a predictive model that identified potentially modifiable
      risk factors for nonelective readmission to a county hospital. The objectives of
      this study were to determine if those risk factors were generalizable to a
      different population. We found that the previously reported risk factors were
      generalizable, and other potentially modifiable risk factors were identified in
      this population of veterans. However, further research is needed to establish
      whether or not the risk factors can be modified and whether or not modification
      improves outcomes.

PMID- 9016427
TI  - Predictors of mortality after acute hip fracture.
AB  - To identify determinants of mortality after hip fracture, we performed a
      multicenter, retrospective study of 390 Medicare beneficiaries. Independent
      predictors of 30-day mortality included a history of congestive heart failure
      (odds ratio [OR] 32; 95% confidence interval [CI] 5, 192), angina (OR 26; 95% CI
      4, 184), or chronic pulmonary disease (OR 11; 95% CI 2, 62). Postoperative use of
      aspirin was associated with a reduced risk of mortality (OR 0.24; 95% CI 0.08,
      0.70). Cardiovascular events were the presumed cause of 63% of in-hospital
      deaths. Aspirin may have significant potential to reduce mortality in this
      population and deserves further study.

PMID- 9016429
TI  - Subclinical hypothyroidism revisited. When is not enough really not enough?

PMID- 9016428
TI  - Should we just let the anticoagulation service do it? The conundrum of
      anticoagulation for atrial fibrillation.

PMID- 9016430
TI  - Looking for asymptomatic abdominal aortic aneurysms.

PMID- 9016431
TI  - Teaching geriatrics to medical residents.

PMID- 9016433
TI  - Quotation accuracy in neuroanesthesiologic research.
AB  - A considerable number of quotational inaccuracies have been detected in medical
      and surgical publications in the past. Our study investigated the quotational
      accuracy of selected references of 32 scientific publications in six anesthesia
      journals referring to a single article published in a 1973 issue of the British
      Journal of Anaesthesia. In four (12.5%) articles, the quotation was in
      contradiction to the primary author's statement; in 15 (46.9%) articles, it was
      selective; and in 13 (40.6%) publications, it was in complete agreement with the
      important statements made in the original article. These results suggest that
      quotational inaccuracy is also evident in neuroanesthesiologic research. This
      problem deserves increased attention by authors as well as by reviewers and
      journal editors.

PMID- 9016432
TI  - Elevated plasma alpha 1-acid glycoprotein levels: lack of connection to
      resistance to vecuronium blockade induced by anticonvulsant therapy.
AB  - This study was designed to investigate the relationships among anticonvulsant
      therapy, plasma alpha 1-acid glycoprotein (AAG) levels, and resistance to
      vecuronium blockade. Thirty-one patients scheduled for routine neurosurgery were
      included in the study. The patients were treated (TG; n = 20) with phenytoin (n =
      15) and/or carbamazepine (n = 4) and/or phenobarbital (n = 3) for > or = 6 days
      or were left untreated (UG; n = 11, control group). TG patients were further
      assigned to one of two subgroups according to the plasma anticonvulsant level
      measured the day before surgery and found to be within (TGW, n = 10) or below
      (TGB, n = 10) the therapeutic range. Finally, the 31 patients were divided into
      two more groups according to their plasma AAG levels: higher than (HAAG, n = 17)
      or within (NAAG, n = 14) the normal range (25-94 mg dl-1). Anesthesia was induced
      and maintained with propofol and sufentanil. Muscle relaxation was obtained with
      vecuronium 0.1 mg kg-1. A train-of-four (TOF) stimulation mode at 2 Hz was
      applied to the ulnar nerve every 15 s, and neuromuscular transmission was
      assessed using a TOF-Guard accelograph monitor. Plasma AAG concentrations (means
      +/- SEM) were 103.7 +/- 7.6 mg dl-1 in TG, 80.7 +/- 6.7 mg dl-1 in UG, 95.9 +/-
      13.2 mg dl-1 in TGW, 111.6 +/- 7.6 mg dl-1 in TGB. 114.9 +/- 7.4 mg dl-1 in HAAG,
      and 71.4 +/- 3.8 mg dl-1 in NAAG groups. The differences in plasma AAG
      concentrations between UG and TG and between HAAG and NAAG groups were
      statistically significant. No significant relationship was found between plasma
      AAG levels and phenytoin concentrations (r = -0.26). The time (mean +/- SEM) to
      recovery of T1 to 25% of control was significantly shorter in TG (28.2 +/- 1.4
      min) than in UG (42.2 +/- 3.1 min) but did not differ significantly according to
      the plasma anticonvulsant level (27.3 +/- 2.0 min in TGW; 29.1 +/- 1.9 min in
      TGB) and the plasma AAG level 31.7 +/- 1.9 min in HAAG; 35.3 +/- 3.3 min in
      NAAG). The time for the TOF ratio to recover to 25% yielded similar profiles and
      statistical significance levels: TG, 32.9 +/- 2.2 min; UG, 51.2 +/- 4.0 min; TGW,
      35.0 +/- 3.9 min; TGB, 30.7 +/- 1.8 min; HAAG, 38.1 +/- 3.1 min; NAAG, 42.0 +/-
      4.1 min. We conclude that anticonvulsant therapy induces an increase in plasma
      AAG independently of the plasma anticonvulsant level. However, duration and
      recovery of vecuronium blockade do not differ according to plasma AAG levels.
      Consequently, elevated AAG does not contribute to the resistance to vecuronium
      blockade induced by anticonvulsants.

PMID- 9016434
TI  - Combined transcranial Doppler and electrophysiologic monitoring for carotid
      endarterectomy.
AB  - The results of carotid endarterectomy can be improved by reducing the
      perioperative embolic and hemodynamic risks. Electrophysiologic monitoring,
      although reliable, cannot provide full information. In this study, we report on
      the combined use of transcranial Doppler (TCD) and electrophysiologic monitoring
      in 153 patients undergoing 166 carotid endarterectomy procedures. TCD monitoring
      confirmed the low incidence of intolerance to cross-clamp (1.8%), showing a good
      correlation with electrophysiologic monitoring. In addition, it frequently showed
      embolic signals immediately after clamp release, but never during carotid
      dissection or in the final operative phases. Furthermore, TCD allowed the
      detection of hyperperfusional flow patterns in four cases, making immediate and
      aggressive control of arterial pressure possible.

PMID- 9016435
TI  - Metabolic consequences of a sorbitol overdose during neurosurgery.
AB  - The authors present a case of severe electrolyte and acid-base disturbances after
      administration of sorbitol. The rate of sorbitol infusion was in excess of the
      stated maximum safe infusion rate in parenteral nutrition. Sorbitol was used for
      treating raised intracranial pressure. The mechanisms of sorbitol metabolism
      leading to hyperlactacemia, lactic acidosis, hyperuricemia, depletion of
      intracellular ATP and ADP and depletion of inorganic phosphates are described.

PMID- 9016436
TI  - Intracisternal papaverine administration associated with acute onset of
      hyperthermia and metabolic acidosis in a craniotomy.
AB  - A case in which the administration of intracisternal papaverine at the end of a
      craniotomy for aneurysm produced a constellation of signs suggestive of malignant
      hyperthermia is presented. The published literature on this subject is reviewed.

PMID- 9016437
TI  - Fluoroscopy-assisted intubation of a child with an unstable subluxation of C1/C2.
AB  - Patients presenting with unstable cervical spine injuries are at risk for
      additional neurological injury as a consequence of airway manipulation.
      Techniques of awake intubation may not always be desirable or practical,
      particularly in the pediatric patient. We describe the use of fluoroscopy during
      the induction of anesthesia and intubation of a child with an unstable C1/C2
      spinal subluxation. Fluoroscopy is readily available and noninvasive. This
      technique allows for rapid establishment and maintenance of optimal head and neck
      positioning during induction of general anesthesia and performance of
      laryngoscopy and tracheal intubation.

PMID- 9016438
TI  - Asystole as a neurologic sign.
AB  - The authors present a case of asystole occurring during dural closure following
      craniotomy with the patient in the supine position. This 22-year-old woman had a
      left parietal lobe tumor resected with bipolar cautery. Standard intraoperative
      monitoring with a left radial arterial line and a right internal jugular central
      venous catheter was used during the surgery. The anesthetic course was
      complicated by intraoperative bleeding that responded to three units of fresh
      frozen plasma. Prior to closure, the operative site appeared dry and intact.
      After closure, asystole occurred suddenly and resolved with evacuation of 500 ml
      of blood. It is speculated that the asystole was preceded by an acute increase in
      intracranial pressure and a subsequent secondary brainstem compression.

PMID- 9016439
TI  - Intravenous lidocaine decreases but cocaine does not alter the rate of
      cerebrospinal fluid formation in anesthetized rabbits.
AB  - Considering that adrenergic stimulation was reported to decrease the rate of
      cerebrospinal fluid (CSF) formation (Vf), it was hypothesized that cocaine might
      exert a similar effect. Accordingly, the present study was designed to examine
      the effects of low, moderate, and high doses of cocaine on Vf and resistance to
      reabsorption of CSF (Ra). Because cocaine possesses both adrenergic-stimulating
      and local anesthetic properties, the present study examined the effects of
      lidocaine, a local anesthetic without adrenergic-stimulating properties, as a
      comparison treatment to cocaine. New Zealand white rabbits (n = 17) weighing 3.5
      4.3 kg were anesthetized with halothane. A needle was inserted into the left
      lateral cerebral ventricle and a catheter was inserted into the cisterna magna to
      permit ventriculocisternal perfusion with mock CSF labeled with blue dextran. A1
      each of four experimental conditions, control and three doses of cocaine or
      lidocaine, fluid volumes and concentrations of blue dextran in timed samples of
      cisternal outflow were used to determine Vf and the rate of reabsorption of CSF
      (Va). In turn, Va at normal and elevated CSF pressures (+6 cmH2O) were used to
      determine Ra. For both the cocaine group (n = 9) and the lidocaine group (n = 8)
      the three drug doses were 0.5 mg.kg-1 followed by 1.0 microgram.kg-1.min-1, 1.5
      mg.kg-1 followed by 3.0 micrograms.kg-1.min-1, and 4.5 mg.kg-1 followed by 9.0
      micrograms.kg-1.min-1 i.v. Cocaine caused no significant change of Vf or Ra. In
      the lidocaine group there was a dose/time-related decrease of Vf (although the
      slope relating Vf to dose/time was not significantly different from that in the
      cocaine group), but no significant change of Ra. It is concluded that during
      halothane anesthesia cocaine does not decrease Vf, a finding not consistent with
      previous reports that adrenergic stimulation decreases Vf. Decrease of Vf with
      lidocaine is consistent with previous reports of similar dose-related effects of
      thiopental, etomidate, midazolam, and fentanyl on Vf.

PMID- 9016440
TI  - Hypervolemic-hemodilution during cerebral ischemia in rats: effect of diaspirin
      cross-linked hemoglobin (DCLHb) on neurologic outcome and infarct volume.
AB  - In a rat model of middle cerebral artery occlusion (MCAo) and reperfusion (120
      min), previous studies have demonstrated that hemodilution with molecular
      hemoglobin decreases ischemic brain injury. However, long-term recovery data on
      the therapeutic efficacy of molecular hemoglobin for cerebral ischemia are
      lacking. Accordingly, we assessed the effect of hemodilution, with alpha-alpha
      diaspirin cross-linked hemoglobin (DCLHb, 10 g/dl) on neurologic outcome and
      infarct volume after 120 min of MCAo and 72 h of reperfusion. Ischemia was
      achieved by passing a 0.26-mm suture, via the external carotid artery, to
      internally occlude the middle cerebral artery. Immediately after MCAo, the rats
      were randomized to one of the following groups: Control-hematocrit not
      manipulated (44%); 30/Hct-hematocrit maintained at 30% with DCLHb; or 16/Hct
      hematocrit maintained at 16% with DCLHb. After 120 min of MCAo, the suture was
      removed and the rats allowed to recover. Daily neurologic examinations were
      performed, and after 72 h, the brains were analyzed for infarct volume with TTC
      stain. Infarct volume (mm3) was less in the 30/Hct group (67 +/- 10; mean +/- SD)
      than in the Control group (141 +/- 17); and less in the 16/Hct group (40 +/- 12)
      than the other two groups (p < 0.05). Neurologic outcome was improved in both
      hemodilution groups versus the Control group (p < 0.05). These data are
      consistent with previous studies, performed in a model of short-term reperfusion,
      which indicate a dose-dependent decrease in ischemic injury by DCLHb.

PMID- 9016441
TI  - Influence of closed head injury on isoflurane MAC in the rat.
AB  - We designed the present study to determine whether the minimum alveolar
      concentration (MAC) for isoflurane is decreased after closed head trauma (CHT) in
      rats and, if so, whether the decrease of MAC is related to the severity of
      neurological impairment following CHT. Isoflurane MAC was determined in 36
      Sprague-Dawley rats. Then, at time = 0 h, animals were grouped. Group 1 (n = 8)
      received no CHT, group 2 (n = 14) received moderate CHT, and group 3 (n = 14)
      received severe CHT. Neurological severity score (NSS, 0 = no deficit and 25 =
      maximal impairment) and MAC were determined at 1, 4, 24, and 48 h. In groups 1
      and 2, isoflurane MAC at 1, 2, 24, and 48 h (1.0-1.1 +/- 0.8-1.2%, median +/-
      range) was not significantly different from baseline (1.0-1.1 +/- 1.0-1.1%). In
      group 3, isoflurane MAC at 1, 2, 24, and 48 h (0.4 +/- 0.2-0.5%) was decreased as
      compared to baseline (1.1 +/- 1.0-1.1%). In group 2, NSS at 1 h was 18 +/- 11-21
      and improved by 48 h to 9 +/- 4-15. In group 3, NSS at 1 h was 24 +/- 22-25 and
      was not significantly different from NSS at 48 h (24 +/- 24-25). Thus, moderate
      CHT does not significantly alter isoflurane MAC, whereas severe CHT equivalent to
      a Glasgow Coma Scale score of 3 to 6 significantly decreases isoflurane MAC.

PMID- 9016442
TI  - Response of cultured cerebral artery smooth muscle cells to the nitric oxide
      vasodilators, nitroglycerin and sodium nitroprusside.
AB  - We characterized the response of soluble guanylyl cyclase in smooth muscle cells
      cultured from cerebral vessels to the nitric oxide (NO)-producing vasodilators,
      nitroglycerin (NTG) and sodium nitroprusside (SNP) and determined the ability of
      these agents to induce tolerance. Smooth muscle cells were isolated from porcine
      basilar, anterior and middle cerebral, and internal carotid arteries. Following
      an initial series of experiments using NTG at various concentrations and times of
      exposure to determine conditions, concentration-response curves of intracellular
      guanosine 3',5'-cyclic monophosphate (cGMP) to NTG and SNP were determined in
      cells pretreated for 1 h with 100 mumol NTG to induce tolerance and compared with
      response curves in control cells. Basal cGMP levels were 2.1 +/- 0.4 pmol/mg cell
      protein (n = 16). Both NTG and SNP increased cGMP in nontolerant cells, and SNP
      was more effective. Maximum concentrations of SNP (1 mmol/L) increased cGMP to
      163 +/- 5.9 pmol/mg versus 21 +/- 2.4 pmol/mg for 1 mmol/L NTG (p < 0.01). Cells
      made tolerant to NTG were unresponsive to NTG up to 1 mmol/L but remained
      responsive to SNP. However, the response curve to SNP was significantly depressed
      by approximately 25%. Following washout of NTG in tolerant cells, the response of
      cGMP to SNP returned to control within 12 h, while response to NTG required 36 h.
      Similar experiments were conducted in cells initially made tolerant to SNP. These
      results indicate that cerebral artery smooth muscle cells in culture express a
      functioning soluble guanylyl cyclase and the enzymes that are necessary to
      metabolize NTG to NO. Prolonged exposure of the cells to NTG induced tolerance as
      well as cross-tolerance to SNP.

PMID- 9016443
TI  - Desflurane and sevoflurane are valuable additions to the practice of
      neuroanesthesiology: pro.

PMID- 9016444
TI  - The new inhalational anesthetics desflurane and sevoflurane are valuable
      additions to the practice of neuroanesthesia: con.

PMID- 9016445
TI  - Cerebral oximetry in dead subjects.

PMID- 9016446
TI  - Vitamin A, visual pigments, and visual receptors in Drosophila.
AB  - The fly visual system has served for decades as a model for receptor spectral
      multiplicity and vitamin A utilization. A diverse armamentarium of structural
      techniques has dovetailed with convenient electrophysiology, photochemistry,
      genetics, and molecular biology in Drosophila to facilitate recent progress,
      which is reviewed here. New data are also presented. Ultrastructure of retinula
      cells of carotenoid-deprived flies shows that organelles associated with protein
      biosynthesis, i.e., rough endoplasmic reticulum and Golgi apparatus, are present,
      while organelles associated with rhabdomere turnover, i.e., multivesicular bodies
      (MVBs), are rare. Ultrastructure and morphometry suggest that retinoic acid
      rearing stimulates membrane export and rhabdomere buildup, even though functional
      rhodopsin is missing. Confocal microscopy suggests that RH4, one of the
      ultraviolet rhodopsins, may reside in the previously-described pale fluorescent
      R7 cells with RH3 in the yellow fluorescent R7 cells.

PMID- 9016447
TI  - Review of larval and postlarval eye ultrastructure in the lamprey (Cyclostomata)
      with special emphasis on Geotria australis (Gray).
AB  - The literature dealing with the lateral eye in lampreys is briefly reviewed here.
      While there appears to be no longer much doubt that the short and long
      photoreceptor cells in the lamprey eye correspond to rods and cones, questions of
      dark/light adaptational changes, the nature of visual pigments, and the roles of
      retinal serotonin and melatonin need to be re-addressed. Eyes of the larval and
      postlarval ("macrophthalmia") stages of the lamprey Geotria australis were
      examined by electron microscopy and it was found that the larval retina is
      largely undifferentiated except for a small central zone surrounding the optic
      nerve head. The retina of the postlarval stage is fully differentiated and the
      photoreceptor outer segments undergo renewal, which appears to involve the
      retinal pigment epithelium (RPE). The distribution of larval RPE and choroidal
      pigments, postlarval ganglion cells, and the orientation of scleral collagen are
      unusual for vertebrates. No obvious positional or size differences of any retinal
      cell type were apparent between day- and night-fixed specimens.

PMID- 9016448
TI  - Distribution of cone photoreceptors in the mammalian retina.
AB  - The retina of mammals contains various amounts of cone photoreceptors that are
      relatively evenly distributed and display a radially or horizontally oriented
      area of peak density. In most mammalian species two spectrally different classes
      of cone can be distinguished with various histochemical and physiological
      methods. These cone classes occur in a relatively constant ratio, middle-to
      longwave sensitive cones being predominant over short-wave cones. Recent
      observations do not support the idea that each cone subpopulation is uniformly
      distributed across the retina. With appropriate type-specific markers, unexpected
      patterns of colour cone topography have been revealed in certain species. In the
      mouse and the rabbit, the "standard" uniform pattern was found to be confined
      exclusively to the dorsal retina. In a ventral zone of variable width all cones
      express short-wave pigment, a phenomenon whose biological significance is not
      known yet. Dorso-ventral asymmetries have been described in lower vertebrates,
      matching the spectral distribution of light reaching the retina from various
      sectors of the visual field. It is not clear, however, whether the retinal cone
      fields in mammals carry out a function similar to that of their counterparts in
      fish and amphibians. Since in a number of mammalian species short-wave cones are
      the first to differentiate, and the expression of the short-wave pigment seems to
      be the default pathway of cone differentiation, we suggest that the short-wave
      sensitive cone fields are rudimentary areas conserving an ancestral stage of the
      photopigment evolution.

PMID- 9016449
TI  - The interphotoreceptor matrix, a space in sight.
AB  - The interphotoreceptor matrix (IPM) has in recent years been receiving much
      attention due to its delicate localization between the photoreceptors and the
      retinal pigment epithelium (RPE). The IPM is a resilient, structure forming and
      hydrophilic matrix composed of large glycoproteins and proteoglycans, which
      occupies the subretinal space between the photoreceptors. The IPM is most likely
      assembled with components synthesized by all the surrounding cell types: the
      photoreceptor cells, the RPE cells, and the Muller cells. It has been implied to
      be involved in the development and maintenance of photoreceptors, and as a major
      factor in retinal adhesion. Therefore, it has been thoroughly studied also in
      several models of photoreceptor degeneration. Comparative studies have revealed
      some remarkably consistent features between different species, such as the
      presence of the rod and cone specific matrix domains. Studies made in the IPM of
      several species have measured large fluctuations in ion concentrations as a
      result of changes in illumination. In some species, these ionic fluctuations
      coincide with the intriguing dynamic redistributions of IPM constituents that can
      be visualized with histochemical techniques. It can be hypothesized that because
      of the intensive biochemical activity and the frequent changes in metabolic
      states of rods and cones the IPM may act as a kind of "buffer." These studies
      have brought a new extracellular aspect to photoreceptor studies and a new
      perspective to photoreceptor-RPE research.

PMID- 9016450
TI  - Plasticity of retinal ribbon synapses.
AB  - Ribbon synapses differ from conventional chemical synapses in that they contain,
      within the cloud of synaptic vesicles (SV's), a specialized synaptic body, most
      often termed synaptic ribbon (SR). This body assumes various forms.
      Reconstructions reveal that what appear as rod- or ribbon-like profiles in
      sections are in fact rectangular or horseshoe-shaped plates. Moreover, spherical,
      T-shaped, table-shaped, and highly pleomorphic bodies may be present. In mammals,
      ribbon synapses are present in afferent synapses of photoreceptors, bipolar nerve
      cells, and hair cells of both the organ of Corti and the vestibular organ.
      Synaptic ribbons (SR's) are also found in the intrinsic cells of the third eye,
      the pineal gland, and in the lateral line system. The precise function of SR's is
      enigmatic. The prevailing concept is that SR's function as conveyor belts to
      channel SV's to the presynaptic membrane for neurotransmitter release by means of
      exocytosis. The present article reviews the evidence that speaks for a plasticity
      of these organelles in the retina and the third eye, as reflected in changes in
      number, size, shape, location, and grouping pattern. SR plasticity is especially
      pronounced in the mammalian and submammalian pineal gland and in cones and
      bipolar cells of teleost fishes. Here, SR number and size wax and wane according
      to the environmental lighting conditions. In the pineal SR numbers increase at
      night and decrease during the day. In teleost cones, SR's are in their prime
      during daytime and decrease or disappear at night, when transmitter release is
      enhanced. In addition to numerical changes, SR's may also exhibit changes in
      size, shape, grouping pattern, and location. In the mammalian retina of adults,
      in contrast to the developing retina, the reported signs of SR plasticity are
      subtle and not always consistent. They may reflect changes in function or may
      represent signs of degradation. To distinguish between the-two, more detailed
      studies under selected experimental conditions are required. Probably the
      strongest evidence for SR plasticity in the mammalian retina is that in
      hibernating squirrels SR's leave the synaptic site and accumulate in areas as far
      as 5 microns from the synapse. Changes in shape include the occurrence of club
      shaped SR's and round SR's or synaptic spheres (SS's). SS's may represent a
      special type of synaptic body, yet belonging to the family of SR's, or may be
      related to the catabolism of SR's. SR number is regulated by Ca2+ in teleost
      cones, whereas in the mammalian pineal gland cGMP is involved. An interesting
      biochemical feature of ribbon synapses is that they lack synapsins. The presently
      reviewed results suggest to us that SR's do not primarily function as conveyor
      belts, but are devices to immobilize SV's in inactive ribbon synapses.

PMID- 9016451
TI  - In vivo microarterial freezing: experimental study.
AB  - In vivo freezing of microarteries with liquid nitrogen is known to relieve spasm
      without inducing thrombosis. In the present study the patency rates of
      microanastomoses in pre- and postfrozen vessels were investigated in the rat
      model. Freezing of the femoral artery was done with ethyl chloride. The artery
      was frozen before the anastomosis was performed on the left side (prefrozen), and
      after on the right side (postfrozen); patency rates were recorded at 2, 10, and
      30 days. Patency rates were 100% in prefrozen vessels and 100% in postfrozen ones
      at all three time intervals. Histologic examination showed depopulation of all
      vessel walls with loss of the intima layer and fragmentation of the inner elastic
      lamina. Progressive cellular repopulation and regeneration of the endothelium
      occurred later, with no differences between pre- and postfrozen arteries. It is
      concluded that freezing of vessels with ethyl chloride reverts arterial spasm
      without inducing thrombosis and that frozen arteries can be repaired by
      microsurgical anastomosis with patency rates comparable to those of virgin
      arteries.

PMID- 9016452
TI  - In vivo microvascular freezing in veins: experimental study.
AB  - In vivo freezing of microarteries is known to relieve spasm without inducing
      thrombosis. In the present study the process of vascular freezing was
      investigated in veins using ethyl chloride in the rat model. Two separate
      experiments were performed. In experiment 1 the epigastric and femoral veins were
      frozen, and the immediate change in diameter was recorded. Patency rates were
      evaluated and specimens harvested at 2, 10, and 30 days. In experiment 2 the
      epigastric and femoral veins were frozen, divided, anastomosed, and examined for
      patency at 72 hours. Patency in frozen epigastric and femoral veins was 100%.
      Pathological findings were loss of intima and part of the media layers, and
      cellular depopulation of the media layer, with progressive regeneration. Increase
      in vein diameter was statistically significant. In experiment 2, patency rates
      were 5% at 72 hours for epigastric veins and 100% for the femoral vein.
      Microthrombi adherent to the wall were demonstrated in all specimens. In
      conclusion, the freezing of microveins relieves spasm without inducing
      thrombosis; the frozen veins can be reliably divided and anastomosed in the
      femoral vein but not in the epigastric vein, the difference being most likely due
      to the different diameter and flow.

PMID- 9016453
TI  - In vivo vascular freezing in clinical microvascular transfer.
AB  - Free flap transfer to the lower limb in chronic post-traumatic conditions is
      known to have a higher complication rate, with flap loss in up to 10% of cases,
      due mainly to the recipient vessels (Godina: Plast Reconstruct Surg 78:285-291,
      1986]). The dissection of these vessels often leads to refractory spasm, due to
      the so-called perivascular post-traumatic disease (PVPTD) (Khouri [Clin Plast
      Surg 19:773-785, 1992]). A case is presented of the use of a fairly new
      spasmolytic maneuver, i.e., in vivo vascular freezing, in a patient who developed
      intractable spasm of the recipient artery.

PMID- 9016454
TI  - Comparison of skeletal muscle microcirculation between clamp ischemia and
      microsurgical ischemia.
AB  - We compared ischemia reperfusion injury-associated vasospasm and perfused
      capillary density (PCD) at the microcirculatory level between clamp ischemia and
      microsurgical ischemia in rat skeletal muscle. Rat cremaster muscle was prepared
      as an island flap, attached only with pudic-epigastric vessels branching from
      external iliac vessels. Two types of ischemia, with clamping only or with
      microvascular anastomosis, were applied at the external iliac vessels for 2 hours
      followed by 1-hour reperfusion before in vivo microscopic examination for
      hemodynamic changes. At the end of observation, small segments of the vessels at
      the clamping site and microsurgical anastomoses site were also harvested for
      histological examination. It was found that the first- and second-order
      arterioles had about 12-15% diameter reductions in both groups, whereas diameter
      reductions of the third-order arterioles were up to 37.8% in the microsurgical
      ischemia group, much greater than that in the clamp ischemia group (2.3%). There
      was also no significant difference in PCD reduction between the two groups,
      although the red blood cell velocity was much slower in the microsurgical
      ischemia group. Histological examination of the anastomosis site showed massive
      accumulation of polymorphonuclear neutrophils on the venous endothelium. These
      results suggested a different degree of endothelial damage and local leukocyte
      activation between microsurgical ischemia and clamp ischemia. Therefore, we
      conclude that clamp ischemia cannot replace microsurgical ischemia for studying
      microcirculatory changes in free tissue transfer.

PMID- 9016455
TI  - Rat intercostal nerves as experimental nerve grafts.
AB  - In this study, we dissected and measured both sets of intercostal nerves
      including lengths, diameters, and axon counts in 12 adult rats to provide data
      applicable to experimental nerve graft research. Dissections showed that total
      lengths of intercostal nerves from the spinal bifurcation to their last
      arborizations near the midline ranged from 10 to 89 mm, and diameters ranged from
      less than 0.1 to 0.5 mm from the thinnest to the thickest part. The segment of
      easiest dissection was the part between the spinal bifurcation and the lateral
      cutaneous branch. This part was 4-27 mm (mean, 13.3 mm) long and had an almost
      constant diameter of 0.18-0.5 mm (mean, 0.32 mm). Counts ranged from 201 to 566
      axons/ nerve. The segment proximal to the lateral cutaneous branch was the most
      convenient part to be harvested as a nerve graft, especially in the 8th to 12th
      intercostal nerves. These nerves could serve as sources for experimental grafts.

PMID- 9016457
TI  - Limiting donor site morbidity by suprafascial dissection of the radial forearm
      flap.
AB  - A technique of suprafascial flap elevation to prevent donor site problems is
      described, based on careful intraoperative observation of the anatomical
      relations of all involved structures in a series of over 400 free forearm flaps
      used in various reconstructive procedures.

PMID- 9016456
TI  - Functional effects of lymphotoxin on crushed peripheral nerve.
AB  - The effect of lymphotoxin (LT) on the functional recovery of crushed peripheral
      nerves was studied. Using a specially designed compression device, a 5 mm segment
      of the right sciatic nerve of rats was subjected to a 100 g crush load with a 2
      hr duration. The rats in the experimental and control groups received two doses
      of LT (20 micrograms/kg each) or the same volume of saline, respectively,
      administered intraperitoneously 24 hr and 1 hr before the procedure. Walking
      track tests and histologic examinations were performed at intervals up to 56 days
      after the crush. Motor functional recovery in the LT pretreated group started at
      day 7 while the crushed limb in the control group remained totally dysfunctional.
      The sciatic functional index improved faster in the LT group than in the control
      group during the second week after the crush and reached a significant difference
      (P < 0.05) at day 18. Subsequently, both groups had a similar evolution.
      Histologic results paralleled the functional findings. In conclusion, LT can
      promote motor functional recovery of crushed rat peripheral nerve in the early
      stage of regeneration.

PMID- 9016458
TI  - Secondary contour reconstruction of maxillectomy defects with a bone graft
      vascularized by flowthrough from radial vascular system.
AB  - We describe post-total maxillectomy secondary facial contour reconstruction using
      an osteocutaneous scapular flap nourished by flow-through vascularization from
      the radial vascular system. Scar contracture caused by either total or partial
      maxillectomy for maxillary cancer was completely released with exposure of the
      edge of the zygomatic arch, orbital floor, and nasal bone. The scapular skin flap
      was placed into the mucosal defect, and the orbital floor and zygomatic
      prominence were reconstructed with the scapular bone. The flap nutrient vessels
      were anastomosed to radial vessels and cephalic vein grafts. Two representative
      cases are illustrated to demonstrate the application and advantage of this
      operative method.

PMID- 9016460
TI  - Free and island flap transfer for soft tissue defects in the hand and forearm.
AB  - Two hundred twenty patients with soft tissue defects in the hand and forearm were
      treated with 226 free and island flap transfers. Reconstructed sites involved the
      thumb in 74 cases, the fingers in 117, the hand in 30, and the forearm in 5.
      Seventy-nine patients received 82 free flaps, and 141 patients received 144
      island flaps. Fifty-six finger reconstruction cases and 73 of 74 thumb
      reconstruction cases had sensory flap transfers. In the free flap transfer group,
      77 flaps survived (93.9%), and 5 failed. In the island flap transfer group, 140
      flaps survived (97.2%), and 4 failed. Of the five-failures in the free flap
      transfers, four were dorsalis pedis flaps, two of which were on patients with an
      arteriovenous fistula. Of the four failures in the island flap transfers, two
      were posterior interosseous flaps and two were digital island flaps. All four
      were reverse-flow island flaps.

PMID- 9016459
TI  - Comparison of end-to-end and end-to-side venous anastomosis in free-tissue
      transfer following resection of head and neck tumors.
AB  - A comparative study was conducted of the results of venous end-to-end and end-to
      side anastomosis in 948 clinical cases of microvascular free-tissue transfers for
      head and neck reconstruction following tumor resection. End-to-side anastomosis
      to the internal jugular vein was achieved uneventfully in the present series,
      while a variety of recipient veins was used for end-to-end anastomosis. The
      incidence of thrombosis was 1.8% (15/835) in the end-to-end anastomosis group and
      2.7% (3/113) in end-to-side venous anastomosis. No statistical difference was
      observed between the two groups. One may hesitate to perform end-to-side
      anastomosis because of unfamiliarity, concern over technical difficulty, and
      unreliability. As a result of our statistical analysis, we are convinced that end
      to-side anastomosis directly to the internal jugular vein, whenever available, is
      the preferred procedure in microvascular free-tissue transfers for reconstruction
      of the head and neck following tumor resection.

PMID- 9016461
TI  - Latissimus dorsi musculocutaneous free flap transplantation to salvage below
      elbow amputation in an emergency operation: a case report.
AB  - We used a free latissimus dorsi musculocutaneous flap (LD m-c flap) to cover a
      large skin defect at the stump of a forearm in an emergency operation. The
      patient we discuss is a 52-year-old man. Amputation at the distal one third of
      the left forearm occurred after catching his hand and wrist in a machine. The
      amputated left hand was severely damaged and there were wide skin defects. The
      function of the elbow joint was well preserved. Both the radius and ulna were cut
      7 cm distal from the elbow joint. A 20 x 8 cm square of LD m-c flap was
      transplanted, to the stump of the forearm. The flap survived without incident.
      The range of motion of the elbow joint was from 20 degrees to 85 degrees. The
      prosthesis was well fitted to the stump, and the patient returned to his workshop
      9 months after injury.

PMID- 9016462
TI  - Reconstruction of the lateral malleolus using a reverse-flow vascularized fibular
      head: a case report.
AB  - We report a case of a 7-year-old girl in whom a vascularized fibular head with
      preserved epiphyseal and metaphyseal blood supply was used to reconstruct the
      missing lateral malleolus. Two-year follow-up showed good bony stability and
      growth potential of the transplanted epiphyseal plate.

PMID- 9016463
TI  - A long-term study of the donor-site ankle after vascularized fibula grafts in
      children.
AB  - We reviewed the long-term course of the donor-site ankle after vascularized
      fibula grafts in 13 children. The preventive and therapeutic effects of the tibio
      fibular metaphyseal synostosis (T-F synostosis) against valgus ankle deformity,
      which is one of the postoperative donor-site problems, were evaluated based on
      three radiologic and clinical parameters. Thirteen patients were divided into two
      groups: patients with or without simultaneous T-F synostosis when the fibula was
      taken. Three patients underwent T-F synostosis secondarily after the development
      of the valgus deformity. Follow-up periods averaged 12.4 years. In the patients
      with primary T-F synostosis, valgus deformity was only observed in one case. No
      functional disorder of the ankle joints was observed after T-F synostosis. In the
      patients without T-F synostosis, all the patients younger than 8 years old showed
      valgus deformity, in which the tilting angle averaged 6.3 degrees. In the three
      patients who underwent T-F synostosis secondarily, the tilting angle normalized
      in cases in which the fixation was performed when the lateral wedging was in a
      mild stage. There was a statistically significant difference in valgus tilt angle
      between the two groups (with or without T-F synostosis).

PMID- 9016464
TI  - Functional outcome of patients with salvageable limbs with grades III-B and III-C
      open fractures of the tibia.
AB  - Numerous reports list predictive criteria to determine whether Gustilio-type
      tibial III-B and III-C fractures of the tibia are salvageable. What is lacking
      are long-term reports of comprehensive functional outcome of these severe
      injuries. We evaluated the functional outcome of patients with our own seven
      scale score. Fifty-four patients with 57 types III-B (n = 41) and III-C (n = 16)
      open tibial fractures sustained between 1980 and 1989 were recalled for
      evaluation. There were 45 men and 9 women (average age, 28.4 years; range, 4-68
      years). Follow-up periods averaged 48.2 months (range, 12-116 months). Salvage
      rate for the III-B fractures was 75% (n = 31) and for the III-C fractures 37% (n
      = 6). We conclude that the functional score is a simple and complete method for
      assessing the functional outcome of patients undergoing limb salvage procedures.

PMID- 9016465
TI  - How should sleeping babies lie?

PMID- 9016466
TI  - Are bedding and rebreathing suffocation a cause of SIDS?
AB  - Suffocation by bedclothes became a popular diagnosis in the 1940s but gradually
      became replaced with the diagnostic label of Sudden Infant Death Syndrome (SIDS).
      In 1991 a paper purported that, instead of SIDS, pillows filled with polystyrene
      beads had caused death by rebreathing suffocation; this conclusion was reached on
      the basis of experiments with anesthetized rabbits breathing through a doll's
      head that was placed face down on the pillow. Because of the anesthesia, rabbits
      could not change their face down position. The doll's nares could not collapse,
      which would have resulted in rapid death due to conventional suffocation. The
      rabbits required up to 3 hours or more to die of hypercarbia and hypoxia. Studies
      in normal infants revealed that they turned from the face-down position after
      only 2 minutes. (The only infant who retained CO2 soon died of a fatal neurologic
      disorder, with central hypoventilation). Using the rabbit/doll's head and
      mechanical models, a wide range of bedding was indicted, including cushions,
      sheepskins, pillows, comforters, foam mattresses, and even simple blankets and
      sheets as potentially causing fatal rebreathing. Except for the use of pillows in
      general, as well as mattresses filled with kapok and bark, there has been no
      epidemiologic support for these indictments. Although normal infants are unlikely
      to succumb to rebreathing suffocation, infants with blunted ventilatory
      responsiveness and delayed arousal due to prior hypoxia were hypothesized to be
      at increased risk. Support for this concept was found in the pathology of the
      brain stem in victims of SIDS that was attributed to prior hypoxic injury. In
      infants who survived prolonged apnea, less than 20% have demonstrated a
      diminished ventilatory responsiveness to hypercarbia, but, more significantly,
      none had an absent response. Arousal to hypercarbia, an abnormality which is
      crucial to the hypothesis of rebreathing suffocation, is regularly present in
      normal subjects, but the threshold is higher in near-SIDS infants; however, no
      instances of failure to arouse have been reported in near-SIDS. If the infant is
      placed on his or her back or side, the issue of bedding could become moot;
      unfortunately, a sizable percentage of infants are still being placed prone for
      sleep. Instead of confusing parents with an ever-expanding list of "dangerous
      bedding," the message "Back to Sleep" should be emphasized.

PMID- 9016467
TI  - The influence of sleeping position on functional residual capacity and effective
      pulmonary blood flow in healthy neonates.
AB  - Variation in body position has been shown to affect respiratory function in
      adults and neonates with and without respiratory illness. At present it remains
      unclear why respiratory function should be affected by different body positions.
      We hypothesized that the effect of body weight on the relatively compliant chest
      wall of the newborn infant in the prone position would cause a reduction in
      functional residual capacity (FRC) and a compensatory improvement in
      ventilation/perfusion matching as measured by effective pulmonary blood flow. To
      evaluate this, a paired crossover study was performed on 12 normal newborn
      infants. The inert gas (argon) rebreathing method adapted for neonates was used
      to measure FRC. Simultaneously effective pulmonary blood flow (Qpeff) was
      determined using Freon 22 and a mass spectrometer with computerized analysis. The
      babies were studied in three different positions in random order: prone, supine
      and right lateral decubitus. The means (95% confidence intervals) of the three
      groups of FRC were 23.8 (19.2 to 28.4), 23.8 (20.2 to 27.5), and 24.3 (19.5 to
      29.2) ml/kg, respectively (P = 0.59) and for Qpeff were 104 (91 to 116), 108 (95
      to 122), 109 (97 to 122) ml/ kg-min, respectively (P = 0.11). Thus no significant
      differences were demonstrated. In nine of the babies, a repeat supine measurement
      was taken at the end of the study to assess repeatability of the method. In these
      nine babies alone the results were 22.7 (19.1 to 26.3) and 22.1 (18.6 to 25.6)
      ml/kg for FRC, and 102 (89 to 116) and 98 (90 to 107) ml/kg-min for Qpeff. The
      coefficients of repeatability were 4.7 ml/kg for FRC (21%) and 30 ml/kg-min for
      Qpeff (30%).

PMID- 9016468
TI  - Surgical treatment of parapneumonic empyema.
AB  - The management of parapneumonic empyema remains controversial. We present the
      management of 20 children with empyema who were referred to The Royal Brompton
      Hospital, over a 5-year period from January 1990 to December 1994. Prior to
      referral, only 12 of the 20 patients had undergone thoracocentesis, all
      confirming the diagnosis of empyema. Six of these 12 patients then underwent
      closed chest tube drainage. There was a 2 to 32 day (median, 8 days) delay from
      initial hospital presentation to referral. Following referral 13 of the 20
      patients were assessed as having persistence of clinical symptoms and
      radiological appearances making recovery with continued conservative management
      unlikely. These patients had a thoracotomy with decortication within 2 days. The
      remaining 7 were initially treated with closed chest tube drainage, but 5
      subsequently required decortication. All patients made an uneventful
      postoperative recovery and were discharged within 3-11 days (mean. 6.8 days) Four
      patients were subsequently found to have a significant underlying immunological
      defect We conclude that there is a lack of agreement regarding the initial
      management of parapneumonic empyema. In our experience, decortication gives
      excellent results in those children not responding to medical treatment within 7
      0 days. In experienced hands this technique is safe with rapid resolution. All
      patients who present with empyema should be screened for immunological
      abnormalities.

PMID- 9016469
TI  - Resistive-load detection in healthy school-aged children.
AB  - The ability to detect changes in respiratory resistance, which may be important
      in acute and chronic adaptations to airways obstruction, has not been measured
      previously in children. Two methods were used to measure the resistive-load
      detection thresholds (the added resistance that produced a "just noticeable
      difference" in perception) in a group of 38 healthy children and adolescents aged
      7-16 years. Total respiratory system resistance (Rrs), as measured by forced
      oscillation, was used as an index of each child's intrinsic baseline (pre-test)
      resistance. To determine thresholds a computer program added various percentages
      of baseline resistance according to response (first method) and then in random
      order (second method). Thresholds by at least one of the two methods were
      detectable in 32 of the children (84%), and failure to detect a threshold was
      less common in older than in young children. Thresholds obtained by each method
      were significantly related to one another (r = 0.54, P < 0.05). Baseline
      resistance accounted for a marginally significant proportion of the variation in
      thresholds as assessed by the tracking method (R2 = 0.12, P < 0.10) and a large
      proportion of the variation in thresholds as assessed by the random method (R2 =
      0.66, P < 0.0001). Thresholds expressed in terms of percent of baseline
      resistance were found to have mean values of 100.4-105.0%, regardless of gender
      or age. Results from a comparison group of adults (n = 10) indicated lower
      threshold by both procedures (mean values, 71.90-76.50%). We conclude that
      perceptual thresholds for added resistive loads are determined, in part, by
      growth-related changes in intrinsic resistance.

PMID- 9016470
TI  - Interpretation of respiratory input impedance in healthy infants.
AB  - Respiratory input impedance (Zin) is a potentially informative test of pulmonary
      function in infants who are unable to perform standard tests commonly performed
      in children and adults Analysis of Zin in dogs using the six-element model of
      DuBois et al. (J Appl Physiol 8:587, 1956) provides estimates of airways
      resistance separate from tissue resistance, as well as an estimate of thoracic
      gas volume. However, reliable estimates of these parameters can only be obtained
      when Zin displays a distinct antiresonance that is associated with the tissue
      inertance and alveolar gas compression compliance. To determine whether infants
      have such an antiresonance. Zin was measured in nine healthy infants (4 < f < 160
      Hz). An antiresonance was found at 112.8-10.4 Hz, and the six-element model fit
      these data well, but the resulting parameters were physiologically unrealistic.
      We hypothesized that the antiresonance in the measured Zin is the result of shunt
      compliance proximal to alveolar gas compression compliance. Gas compression in
      the face mask and nonrigid upper airway walls could provide such a shunt
      compliance. We investigated another model with four parameters, a single shunt
      compliance (Cim) representing gas compression in the face mask in parallel with
      the infant's total respiratory resistance (Rrs) inertance (Irs), and compliance
      (Crs). This model fits the data well, and the estimated R, (19.3, 4.2 cmH O/L/s)
      was physiologically reasonable. However, Crs (Crs 1.03-0.58 mL cmH2O) was one
      order of magnitude smaller than reported Crs. The value for Cim was slightly
      larger than that based on the estimated volume of gas in the face mask,
      suggesting an additional influence of upper airway wall shunting. Computer
      simulations using a model that includes the face mask and upper airway walls
      confirmed that Cim and the upper airway wall properties significantly influence
      Zin data over this frequency range. Nevertheless, these simulations suggest that
      the Rrs estimated from the four-element model is related to airway resistance.

PMID- 9016472
TI  - Genotype-phenotype correlations in cystic fibrosis.

PMID- 9016471
TI  - Exogenous surfactant decreases oxygenation in Escherichia coli endotoxin-treated
      neonatal piglets.
AB  - Abnormalities of pulmonary surfactant function have been described in association
      with the acute respiratory distress syndrome (ARDS). Because gram-negative sepsis
      is a common cause of ARDS, we treated neonatal piglets with Escherichia coli
      endotoxin to create a neonatal ARDS model. We hypothesized that under these
      conditions administration of exogenous surfactant would improve pulmonary
      function. Study groups included: control (n-8), Exosurf (5 mL/kg, 13.5 mg
      phospholipid/mL, n-7), Survanta (4 mL/kg, 25 mg phospholipid/mL, n-6), and saline
      (5 mL/kg, n = 6). E. coli endotoxin 12 micrograms/kg was infused over 30 min and
      resulted in significant pulmonary and hemodynamic abnormalities, histopathologic
      evidence of nonhomogeneous lung injury, and elevated protein levels in
      bronchoalveolar lavage washings. Neither Exosurf nor Survanta ameliorated the
      pulmonary effects of endotoxin. Instead, there was a prolonged decrease in
      arterial oxygen tension (PaO2) and dynamic lung compliance after administration
      of surfactant and saline. Distribution of a bolus of Exosurf was uneven
      throughout the lung. We conclude that in this neonatal piglet model of ARDS,
      bolus surfactant administration had a detrimental effect on oxygenation and
      pulmonary function.

PMID- 9016473
TI  - Measurement of expired nitric oxide levels in children.
AB  - Nitric oxide (NO) can be measured directly in expired air in adults. The purpose
      of our study was to measure NO levels in children and to compare these values
      with adults. Exhaled NO was measured in 39 normal prepubertal children (23
      girls), aged 9-11 years (mean 9.9 years). Exhaled NO was measured by the
      chemiluminescence method that is sensitive in a range of 2 to 4,000 ppb of NO on
      an adapted analyzer (Dasibi Environmental). Wearing a nose clip. 5 measurements
      were recorded in each child with exhalation 1) directly into the NO analyzer
      (flow rate 240 mL/min) with measurements of NO, carbon dioxide, and mouth
      pressure; and 2) using a T-piece to allow measurements at a different flow rate.
      For all measurements, background NO levels were less than 10 ppb. The mean direct
      level was 49.6 ppb, SD 37.8 (range, 11.5-197.2 ppb) compared with T-piece levels
      of 29.2 ppb. SD 27.1 (range, 5.1-141.2 ppb). There was no significant difference
      between boys and girls for direct or T-piece recordings. Mean direct NO in boys
      was 43.1 ppb, SD 40.5 and in girls 55.2 ppb, SD 35.4; mean T-piece in boys was
      25.6 ppb. SD 29.2 and in girls 33.8 ppb, SD 25.1. Mean NO levels in prepubertal
      children are lower than in adults and show no difference between males and
      females.

PMID- 9016474
TI  - Comparison of sputum processing techniques in cystic fibrosis.
AB  - Sputum analysis is a useful technique for the study of airway inflammation. In
      asthma, dithiothreitol (DTT) is used to disperse cells from surrounding mucus;
      however, the applicability of these processing methods to cystic fibrosis (CF)
      sputum is unknown. In order to compare two methods for processing sputum of
      patients with CF, sputum was obtained from 11 subjects with CF (8 female, aged 9
      21 years). The sample was split into 2 portions and sputum dispersal using DTT
      was compared with an enzyme mixture (E) of deoxyribonuclease, hyaluronidase, and
      galactosidase. Outcomes assessed were sample quality, cell viability (percent
      cells excluding trypan blue), total cell count (TCC), neutrophil count, and
      elastase immunoreactivity (percent cells positive). Sample quality (enzymes vs.
      DTT, 8.3 +/- 0.3 vs 7.6 +/- 0.4, mean +/- SEM) and cell viability (enzymes vs.
      DTT, 75.0% vs. 68.0%, median) were similar for both methods. Sputum total cell
      count (20.5 x 10(6)/ml vs. 12.0 x 10(6)/ml, median; P = 0.01) and neutrophil
      count (13.4 x 10(6)/ml vs. 5.5 > 10(6)/ml, median; P = 0.02) were significantly
      higher with E. Elastase immunoreactivity was lost after processing with E (19.0%
      vs. 39.5%, median; P = 0.04). When purified peripheral blood neutrophils were
      incubated with DTT and E, there was no reduction in neutrophil viability,
      suggesting that the reduced neutrophil number in CF sputum was not due to a toxic
      effect of DTT but rather incomplete dispersal. We conclude that published sputum
      processing methods for asthma using DTT give false results when applied to CF
      sputum, which should be processed using an enzyme mixture.

PMID- 9016475
TI  - A rare tumor masquerading as an empyema: pleuropulmonary blastoma.
AB  - Pleuropulmonary blastoma, although rare, should be considered in the differential
      diagnosis of children who present with a pleural effusion and symptoms of
      respiratory tract infection when the empyema fails to respond to medical
      management. A case of a 2-year-old boy with this rapidly growing tumor is
      reported. The treatment and outcome of pleuropulmonary blastoma in children is
      reviewed.

PMID- 9016476
TI  - Treatment of respiratory failure due to respiratory syncytial virus pneumonia
      with natural surfactant.
AB  - We describe two infants suffering from severe pneumonia caused by respiratory
      syncytial virus (RSV) infection and needing mechanical ventilation with both high
      ventilator settings and a high fraction of inspired oxygen. The severity of the
      respiratory failure and the possibility of decreased and/or altered surfactant
      production led us to treat these infants with intratracheal instillation of
      natural surfactant. This resulted in an improvement of lung compliance and a
      decrease in the amount of oxygen required to maintain acceptable oxygen
      saturations. Intratracheal surfactant instillation might, therefore, be useful in
      the treatment of severe RSV pneumonia.

PMID- 9016477
TI  - Major hemoptysis in a child with cystic fibrosis from multiple aberrant bronchial
      arteries treated with tranexamic acid.

PMID- 9016478
TI  - Stretch shorten cycle performance: detrimental effects of not equating the
      natural and movement frequencies.
AB  - This study aimed to assess whether the benefits associated with stretch shorten
      cycle (SSC) movements required the movement frequency to be in resonance with the
      natural frequency of the elastic structures. Seventeen untrained participants
      performed SSC and concentric bench press throws. Further, quasi-static muscular
      actions were also performed in which a brief perturbation was applied to the bar
      with the resulting damped oscillations providing natural frequency data. It was
      observed that prior stretch did not facilitate concentric performance. Further,
      there were large significant differences between the natural frequency of the
      musculo-tendinous system and the frequency of the SSC movements. The authors
      hypothesize that the failure to achieve resonance contributed to the poor
      performance achieved in the SSC actions.

PMID- 9016479
TI  - Sports, exercise, and other causes of injuries: results of a population survey.
AB  - Mortality rates and injuries requiring medical treatment associated with sports
      and exercise are generally low. However, higher injury rates are reported for
      athletes and members of sports clubs. This study focuses on the sport- and
      exercise-related injury rate for various age and sex groups in the general
      population and how sport and exercise injury rates compare with those for other
      activities. The data presented are based on telephone interviews. Of the
      participants (N = 6,596), 335 (5.1%) reported having sustained an injury in the
      previous month; 46% of injuries among males and 14% of those among females were
      sport or exercise related. The data show a downward trend in sport- and exercise
      related injury rates with increasing age. It is concluded that, as a proportion
      of all injuries sustained, the sport- and exercise-related injury rate is high,
      particularly among males. Possible future research on sport- and exercise-related
      injuries is discussed.

PMID- 9016481
TI  - Testing the simplex assumption underlying the Sport Motivation Scale: a
      structural equation modeling analysis.
AB  - Self-determination theory (Deci & Ryan, 1985) suggests that motivational
      orientation or regulatory styles with respect to various behaviors can be
      conceptualized along a continuum ranging from low (a motivation) to high
      (intrinsic motivation) levels of self-determination. This pattern is manifested
      in the rank order of correlations among these regulatory styles (i.e., adjacent
      correlations are expected to be higher than those more distant) and is known as a
      simplex structure. Using responses from the Sport Motivation Scale (Pelletier et
      al., 1995) obtained from a sample of 857 college students (442 men, 415 women),
      the present study tested the simplex structure underlying SMS subscales via
      structural equation modeling. Results confirmed the simplex model structure,
      indicating that the various motivational constructs are empirically organized
      from low to high self-determination. The simplex pattern was further found to be
      invariant across gender. Findings from this study support the construct validity
      of the SMS and have important implications for studies focusing on the influence
      of motivational orientation in sport.

PMID- 9016480
TI  - Knowledge representation and problem solution in expert and novice youth baseball
      players.
AB  - The purpose of this study was to examine differences in knowledge representation
      and problem solutions in expert and novice youth baseball players. Ninety-four
      players in two age divisions, 7-8 years of age and 9-10 years of age, were
      assigned to three levels of expertise: high; average; and low skilled. Each
      subject participated in an interview session to elicit knowledge representation
      and solutions to five different defensive game situations. Interviews were
      transcribed and analyzed for content, solution to the problem, errors in problem
      solution, and qualitative trends. The frequency of advanced solutions to each of
      the five situations were analyzed in separate chi-square tests for age and
      expertise. Differences among the levels of expertise were found for the accuracy
      of solutions to three complex situations. Age was significant for only one
      situation. Patterns of knowledge content accessed during advanced and less
      advanced responses indicated both experts and novices were in a beginning stage
      of developing baseball knowledge structures. Errors in problem solutions
      indicated children had difficulty monitoring critical conditions and making
      correct inferences. Players' and teammates' ability to execute baseball skills
      seemed to influence the content and structure of tactical knowledge accessed
      during problem solution.

PMID- 9016482
TI  - Development, application, and limitation of a stochastic Markov model in
      explaining championship squash performance.
AB  - This study reports a stochastic (Markov) model for squash which uses empirical
      data to transit event states on a shot by shot basis. This offers more
      information than traditional models with regard to how points were won or lost
      and the potential for predicting future athletic performance from a priori
      observation. The predictive capacity of the model, however, is presently
      restricted because the observed behaviors (shots) and associated outcomes
      (winners, errors and lets) are statistically variant (p < .25). A player does not
      produce a consistent athletic response to the same preceding condition when
      competing against different opponents, although it is unclear at present whether
      this observation is a function of the particular analysis employed. Nevertheless,
      the modeling of athletic behavior is a way to search for critical data which
      underpin competitive sport performance.

PMID- 9016483
TI  - Delayed visual feedback while learning to track a moving target.
AB  - Two studies investigated the effects of delayed visual feedback on manual
      tracking. In Experiment 1, individuals practiced with visual feedback provided
      either immediately (0 delay) or with a 333-ms delay. During acquisition, the 0
      delay group performed with less error than the 333-ms delay group. A retention
      test with 0 delay feedback was performed with the least error by the 0 delay
      group. A transfer test using a different 0 delay tracking pattern, was performed
      with the least error by the 333-ms delay group. In Experiment 2, individuals
      practiced at six different delays. Error increased as training feedback delay
      increased. For retention there were no differences between the delay groups
      during the 0 delay retention. At a 417-ms retention, test error decreased as
      training feedback delay increased. Results indicate that error during acquisition
      does not necessarily impair learning and that feedback delays can be beneficial
      for learning.

PMID- 9016484
TI  - Student interest in activities in a secondary physical education curriculum: an
      analysis of student subjectivity.
AB  - Situational interest is defined as a student's perception of interest inherent in
      an activity. Holding interest is conceptualized as a specific situational
      interest perceived by a student based on his or her subjective understanding of
      the activity's meaningfulness. It motivates the student to continuously
      participate in that activity. This research was designed to examine the patterns
      of holding interest for physical activities in a state physical education
      curriculum for secondary schools. A group of college students (N = 35) who
      completed their entire secondary education in the state was invited to construct
      their perceptions of interest in the activities selected from their secondary
      physical education curriculum. Q methodology was used to determine and analyze
      patterns of the interest. Four patterns of holding interest were determined:
      fitness, socialization, activity variation, and self-expression. Specific
      activities associated with each pattern were identified, and relationships among
      the four patterns were described. Findings (a) support the notion that holding
      interest is based on students' subjective understanding and valuing of the unique
      meanings in physical activities and (b) suggest that holding interest is person-
      and activity-specific, implying that physical educators should focus on student
      activity matching when making curricular decisions.

PMID- 9016485
TI  - Exploring practical knowledge: a case study of an experienced senior tennis
      performer.
AB  - The purpose of the study was to explore sport-related practical knowledge through
      the perceptions and experiences of a senior adult competitive tennis performer.
      Practical knowledge was defined as goal oriented, experiential knowledge
      developed within particular physical activity settings. Data were collected
      through formal interviews and participant observation and analyzed through
      narrative inquiry and conventional coding techniques. The data suggest that the
      tennis environment was perceived in terms of the opportunities afforded by that
      environment. Specifically, the participant's practical knowledge centered on
      performance capabilities and strategic planning that revealed opponent
      limitations. This knowledge appeared to be developed and expressed within the
      relationships among individual capabilities, the task, and the situated context
      of game play.

PMID- 9016486
TI  - The validity and reliability of the back saver sit-and-reach test in middle
      school girls and boys.

PMID- 9016487
TI  - Alternative approach to maximal exercise testing and VO2 max prediction in
      college students.

PMID- 9016488
TI  - Optimal movement pattern characteristics are not required as a reference for
      knowledge of performance.

PMID- 9016489
TI  - The energy cost associated with selected step training exercise techniques.

PMID- 9016490
TI  - The effect of adding external weight on the aerobic requirement of bench
      stepping.

PMID- 9016491
TI  - GenBank.
AB  - The GenBank sequence database incorporates DNA sequences from all available
      public sources, primarily through the direct submission of sequence data from
      authors and from large-scale sequencing projects. Data exchange with the EMBL
      Data Library and the DNA Data Bank of Japan helps ensure comprehensive coverage.
      GenBank continues to focus on quality control and annotation while expanding data
      coverage and retrieval services. An integrated retrieval system, known asEntrez,
      incorporates data from the major DNA and protein sequence databases, along with
      genome maps and protein structure information. MEDLINE abstracts from published
      articles describing the sequences are also included as an additional source of
      biological annotation. Sequence similarity searching is offered through the BLAST
      family of programs. All of NCBI's services are offered through the World Wide
      Web. In addition, there are specialized server/client versions as well as FTP and
      e-mail server access.

PMID- 9016494
TI  - DNA Data Bank of Japan in the age of information biology.
AB  - DNA Data Bank of Japan (DDBJ) began its activities in 1986 in collaboration with
      EMBL in Europe and GenBank in the United States. DDBJ developed a data submission
      tool called Sakura, by which researchers can submit their newly sequenced data on
      WWW from every corner of the world. The data bank also built a database
      management system (Yamato II), incorporating the techniques and functions of the
      object-oriented database, in order to efficiently process the data it has
      collected. A number of research activities in information biology are also going
      on at DDBJ. Two such activities are also briefly introduced in this report.

PMID- 9016496
TI  - The Genome Sequence DataBase version 1.0 (GSDB): from low pass sequences to
      complete genomes.
AB  - The Genome Sequence DataBase (GSDB) has completed its conversion to an improved
      relational database. The new database, GSDB 1.0, is fully operational and
      publicly available. Data contributions, including both original sequence
      submissions and community annotation, are being accomplished through the use of a
      graphical client-server interface tool, the GSDB Annotator, and via GIO (GSDB
      Input/Output) files. Data retrieval services are being provided through a new Web
      Query Tool and direct SQL. All methods of data contribution and data retrieval
      fully support the new data types that have been incorporated into GSDB, including
      discontiguous sequences, multiple sequence alignments, and community annotation.

PMID- 9016493
TI  - The EMBL Nucleotide Sequence Database.
AB  - The EMBL Nucleotide Sequence Database is a comprehensive database of DNA and RNA
      sequences directly submitted from researchers and genome sequencing groups and
      collected from the scientific literature and patent applications. In
      collaboration with DDBJ and GenBank the database is produced, maintained and
      distributed at the European Bioinformatics Institute (EBI) and constitutes
      Europe's primary nucleotide sequence resource. Database releases are produced
      quarterly and are distributed on CD-ROM. EBI's network services allow access to
      the most up-to-date data collection via Internet and World Wide Web interface,
      providing database searching and sequence similarity facilities plus access to a
      large number of additional databases.

PMID- 9016497
TI  - The Protein Information Resource (PIR) and the PIR-International Protein Sequence
      Database.
AB  - From its origin, the PIR has aspired to support research in computational biology
      and genomics through the compilation of a comprehensive, quality controlled and
      well-organized protein sequence information resource. The resource originated
      with the pioneering work of the late Margaret O. Dayhoff in the early 1960s.
      Since 1988, the Protein Sequence Database has been maintained collaboratively by
      PIR-International, an association of macromolecular sequence data collection
      centers dedicated to fostering international cooperation as an essential element
      in the development of scientific databases. The work of the resource is widely
      distributed and is available on the World Wide Web, via FTP, E-mail server, CD
      ROM and magnetic media. It is widely redistributed and incorporated into many
      other protein sequence data compilations including SWISS-PROT and theEntrezsystem
      of the NCBI.

PMID- 9016498
TI  - MIPS: a database for protein sequences, homology data and yeast genome
      information.
AB  - The MIPS group (Martinsried Institute for Protein Sequences) at the Max-Planck
      Institute for Biochemistry, Martinsried near Munich, Germany, collects, processes
      and distributes protein sequence data within the framework of the tripartite
      association of the PIR-International Protein Sequence Database (,). MIPS
      contributes nearly 50% of the data input to the PIR-International Protein
      Sequence Database. The database is distributed on CD-ROM together with PATCHX, an
      exhaustive supplement of unique, unverified protein sequences from external
      sources compiled by MIPS. Through its WWW server (http://www.mips.biochem.mpg.de/
      ) MIPS permits internet access to sequence databases, homology data and to yeast
      genome information. (i) Sequence similarity results from the FASTA program () are
      stored in the FASTA database for all proteins from PIR-International and PATCHX.
      The database is dynamically maintained and permits instant access to FASTA
      results. (ii) Starting with FASTA database queries, proteins have been classified
      into families and superfamilies (PROT-FAM). (iii) The HPT (hashed position tree)
      data structure () developed at MIPS is a new approach for rapid sequence and
      pattern searching. (iv) MIPS provides access to the sequence and annotation of
      the complete yeast genome (), the functional classification of yeast genes
      (FunCat) and its graphical display, the 'Genome Browser' (). A CD-ROM based on
      the JAVA programming language providing dynamic interactive access to the yeast
      genome and the related protein sequences has been compiled and is available on
      request.

PMID- 9016499
TI  - The SWISS-PROT protein sequence data bank and its supplement TrEMBL.
AB  - SWISS-PROT is a curated protein sequence database which strives to provide a high
      level of annotations (such as the description of the function of a protein,
      structure of its domains, post-translational modifications, variants, etc.), a
      minimal level of redundancy and high level of integration with other databases.
      Recent developments of the database include: an increase in the number and scope
      of model organisms; cross-references to two additional databases; a variety of
      new documentation files and the creation of TrEMBL, a computer annotated
      supplement to SWISS-PROT. This supplement consists of entries in SWISS-PROT-like
      format derived from the translation of all coding sequences (CDS) in the EMBL
      nucleotide sequence database, except the CDS already included in SWISS-PROT.

PMID- 9016500
TI  - The metabolic pathway collection: an update.
AB  - The Metabolic Pathway Collection from EMP is an extraction of data from the
      larger Enzymes and Metabolic Pathways database (EMP). This extraction has been
      made publicly available in the hope that others will find it useful for a variety
      of purposes. The original release in October 1995 contained 1814 distinct
      pathways. The current collection contains 2180. Metabolic reconstructions for the
      first completely sequenced organisms-Haemophilus influenzae,Mycoplasma
      genitalium,Saccharomyces cerevisiaeandMethanococcus janaschii-are all included in
      the current release. All of the pathways in the collections are available as
      ASCII files in the form generated by the main curator, Evgeni Selkov. In
      addition, we are offering a more structured encoding of a subset of the
      collection; our initial release of this subcollection includes all of the
      pathways inMycoplasma genitalium, and we ultimately intend to offer the entire
      collection in this form as well.

PMID- 9016501
TI  - Compilation of DNA sequences of Escherichia coli K12: description of the
      interactive databases ECD and ECDC (update 1996).
AB  - We have compiled the DNA sequence data forEscherichia coliavailable from the
      GenBank and EMBL data libraries and independently from the literature. We provide
      the most definitive version of the ECDEscherichia colidatabase now exclusively
      via the World Wide Web System: http://susi.bio.uni-giessen.de/usr/local/www/
      html/ecdc.html . Our database encloses an assembled set of contiguous sequences.
      Each of these contigs compiles all available sequence information, including
      those derived from a variety of elder sequences. The organisation of the database
      allows precise physical location of each individual gene or regulatory region,
      even taking into consideration discrepancies in nomenclature. The WWW program
      allows to branch into the original EMBL and SWISSPROT datafiles. A number of
      links to other WWW servers is provided. A FASTA and BLAST search may be performed
      online. Besides the WWW format a flat file version may be obtained via ftp. The
      ftp version may also be obtained from the EMBL data library as part of the CD-ROM
      issue of the EMBL sequence database, which is released and updated every 3
      months. After deletion of all detected overlaps a total of 3 588 706 individual
      bp has been determined up to the end of September 1996. This corresponds to a
      total of 77.09% of the entire E.coli chromosome consisting of approximately 4655
      kb. About 479 kb (10.3%) are additionally available from Kyoto (Japan). Another
      94 kb (2%) are available, but mapping has not been confirmed. Thus the total may
      have reached 89.4%.

PMID- 9016502
TI  - EcoCyc: Enyclopedia of Escherichia coli Genes and Metabolism.
AB  - The Encyclopedia of Genes and Metabolism (EcoCyc) is a database that combines
      information about the genome and the intermediary metabolism of Escherichia coli.
      It describes 2970 genes of E.coli, 547 enzymes encoded by these genes, 702
      metabolic reactions that occur in E.coli and the organization of these reactions
      into 107 metabolic pathways. The EcoCyc graphical user interface allows
      scientists to query and explore the EcoCyc database using visualization tools
      such as genomic-map browsers and automatic layouts of metabolic pathways. EcoCyc
      spans the space from sequence to function to allow scientists to investigate an
      unusually broad range of questions. EcoCyc can be thought of as both an
      electronic review article because of its copious references to the primary
      literature, and as an in silicio model of E.coli metabolism that can be probed
      and analyzed through computational means.

PMID- 9016503
TI  - Genes and proteins of Escherichia coli K-12 (GenProtEC).
AB  - GenProtEC is a database of Escherichia coli genes and their gene products,
      classified by type of function and physiological role and with citations to the
      literature for each. Also present are data on sequence similarities
      amongE.coliproteins with PAM values, percent identity of amino acids, length of
      alignment and percent aligned. GenProtEC can also be accessed through the World
      Wide Web at URL http://mbl.edu/html/ecoli.html .

PMID- 9016505
TI  - Yeast Protein database (YPD): a database for the complete proteome of
      Saccharomyces cerevisiae.
AB  - The Yeast Protein Database (YPD) is a database for the proteins of the budding
      yeast,Saccharomyces cerevisiae. YPD is the first annotated database for the
      complete proteome of any organism. Now that the complete genome sequence of yeast
      is available, YPD contains entries for each of the characterized proteins and for
      each of the uncharacterized proteins predicted from the sequence. Contained in
      YPD are the calculated properties of each protein such as molecular weight and
      isoelectric point, experimentally determined properties such as subcellular
      localization and post-translational modifications, and extensive annotations from
      the yeast literature. YPD contains 25 000 lines of textual annotation that
      describe the known functions, mutant phenotypes, interactions, and other
      properties for the approximately 6000 proteins in the yeast proteome. The
      information in YPD is updated daily, and it is available on the World Wide Web at
      http://www.proteome.com/YPDhome.html .

PMID- 9016504
TI  - The NRSub database: update 1997.
AB  - In the context of the international project aiming at sequencing the whole genome
      of Bacillus subtilis we have developed NRSub, a non-redundant database of
      sequences from this organism. Starting from the B.subtilis sequences available in
      the repository collections we have removed all encountered duplications, then we
      have added extra annotations to the sequences (e.g. accession numbers for the
      genes, locations on the genetic map, codon usage index). We have also added cross
      references with EMBL/GenBank/DDBJ, MEDLINE, SWISS-PROT and ENZYME databases.
      NRSub is distributed through anonymous FTP as a text file in EMBL format and as
      an ACNUC database. It is also possible to access the database through two
      dedicated World Wide Web servers located in France (http://acnuc.univ
      lyon1.fr/nrsub/nrsub.++ +html ) and in Japan (http://ddbjs4h.genes.nig.ac.jp/ ).

PMID- 9016506
TI  - GIF-DB, a WWW database on gene interactions involved in Drosophila melanogaster
      development.
AB  - GIF-DB (Gene Interactions in the Fly Database) is a new WWW database (http://www
      biol.univ-mrs.fr/ approximately lgpd/GIFTS_home_page. html ) describing gene
      molecular interactions involved in the process of embryonic pattern formation in
      the flyDrosophila melanogaster. The detailed information is distributed in
      specific lines arranged into an EMBL- (or SWISS-PROT-) like format. GIF-DB
      achieves a high level of integration with other databases such as FlyBase, EMBL
      and SWISS-PROT through numerous hyperlinks. The original concept of interaction
      databases examplified by GIF-DB could be extended to other biological subjects
      and organisms so as to study gene regulatory networks in an evolutionary
      perspective.

PMID- 9016507
TI  - The GDB Human Genome Database Anno 1997.
AB  - The value of the Genome Database (GDB) for the human genome research community
      has been greatly increased since the release of version 6. 0 last year. Thanks to
      the introduction of significant technical improvements, GDB has seen dramatic
      growth in the type and volume of information stored in the database. This article
      summarizes the types of data that are now available in the Genome Database,
      demonstrates how the database is interconnected with other biomedical resources
      on the World Wide Web, discusses how researchers can contribute new or updated
      information to the database, and describes our current efforts as well as planned
      improvements for the future.

PMID- 9016508
TI  - The Radiation Hybrid Database.
AB  - Since July 1995, the European Bioinformatics Institute (EBI) has maintained RHdb,
      a public database for radiation hybrid data. Radiation hybrid data are used in
      the generation of alternative genetic maps as they can include non-polymorphic
      markers and are also powerful enough to order unresolved genetic clusters of
      polymorphic STSs. The EBI is an Outstation of the European Molecular Biology
      Laboratory (EMBL).

PMID- 9016509
TI  - Molecular Probe Data Base (MPDB).
AB  - Molecular Probe Data Base contains detailed information on synthetic
      oligonucleotides with a sequence of up to 100 nucleotides. This database
      prevalently contains information related to human oligonucleotides used in
      diagnostics. Molecular Probe Data Base has been made available on-line through
      the Internet by means of Network Information Retrieval (NIR) tools since 1993.
      Two years ago, a collaboration with EMBL Data Library was also set up, so that
      the Molecular Probe Data Base has been integrated with other molecular biology
      data banks in the sphere of the SRS WWW network browser. In this paper, the most
      recent enhancements and the current status of the Molecular Probe Data Base are
      briefly presented.

PMID- 9016510
TI  - Compilation of 5S rRNA and 5S rRNA gene sequences.
AB  - The compilation of 5S rRNA and 5S rRNA gene nucleotide sequences as of 30
      September 1996, contains a total of 1661 primary structures of 5S rRNAs or their
      genes, which is an increase of 928 new sequence entries over the last
      compilation. It covers sequences from 54 archaea, 449 eubacteria, 34 plastids,
      nine mitochondria and 430 eukaryotes. The databank uses the format of the EMBL
      Nucleotide Sequence Data Library complemented by a Sequence Alignment (SA) field
      including secondary structure information. The taxonomic classification of
      organisms was totally updated. Now the database is also available via anonymous
      FTP or WWW.

PMID- 9016512
TI  - The uRNA database.
AB  - The uRNADB offers aligned, annotated and phylogenetically ordered sequences of
      several U RNAs. New to this release are RNAs from U7 (14 sequences), U8 (two
      sequences), U11 (three sequences), U12 (two sequences), U14 (11 sequences), U18,
      U48 and U49. A total of 34 new sequences were aligned with the previously
      compiled snRNAs U1, U2, U3, U4, U5 and U6.

PMID- 9016511
TI  - Small RNA database.
AB  - The small RNA database is a compilation of all the small size RNA sequences
      available to date, including nuclear, nucleolar, cytoplasmic and mitochondrial
      small RNAs from eukaryotic organisms and small RNAs from prokaryotic cells as
      well as viruses. Currently, about 600 small RNA sequences are in our database. It
      also gives the sources of individual RNAs and their GenBank accession numbers.
      The small RNA database can be accessed through WWW(World Wide Web). Our WWW URL
      address is: http://mbcr.bcm.tmc.edu/smallRNA/smallrna. html . The new small RNA
      sequences published since our last compilation are listed in this paper.

PMID- 9016513
TI  - The guide RNA database.
AB  - The RNA editing process in protozoan parasites is controlled by small RNA
      molecules known as guide RNAs (gRNAs). The gRNA database is a comprehensive
      compilation of published guide RNA sequences from eight different kinetoplastid
      organisms. In addition to the RNA primary sequences, information on the gene
      localization, the experimental verification of the transcripts, and literature
      citations are provided. Accessory information includes the secondary structures
      of fourTrypanosoma bruceigRNAs as well as a computer modelled three dimensional
      gRNA structure. The database is made available as a hypertext document accessible
      via the World Wide Web (WWW) or from the authors in a printed form.

PMID- 9016514
TI  - The Signal Recognition Particle Database (SRPDB).
AB  - The SRPDB (Signal Recognition Particle Database) offers aligned SRP RNA and SRP
      protein sequences, phylogenetically ordered and annotated. This release adds
      three SRP RNA sequences (totaling 96 SRP RNA sequences) and 11 SRP protein
      sequences (a total of 39 protein sequences from SRP9, SRP14, SRP19, SRP21, SRP54,
      SRP68 or SRP72). Also downloadable are sample SRP RNA secondary structure
      diagrams, a three-dimensional model of the human SRP RNA, search motifs and
      software.

PMID- 9016515
TI  - The RDP (Ribosomal Database Project).
AB  - The Ribosomal Database Project (RDP) is a curated database that offers ribosome
      related data, analysis services and associated computer programs. The offerings
      include phylogenetically ordered alignments of ribosomal RNA (rRNA) sequences,
      derived phylogenetic trees, rRNA secondary structure diagrams, and various
      software for handling, analyzing and displaying alignments and trees. The data
      are available via anonymous FTP (rdp.life.uiuc.edu), electronic mail
      (server@rdp.life.uiuc.edu), gopher (rdpgopher.life.uiuc.edu) and WWW
      (http://rdpwww.life.uiuc.edu/ ). The electronic mail and WWW servers provide
      ribosomal probe checking, approximate phylogenetic placement of user-submitted
      sequences, screening for possible chimeric rRNA sequences, automated alignment,
      and a suggested placement of an unknown sequence on an existing phylogenetic
      tree.

PMID- 9016516
TI  - Database on the structure of small ribosomal subunit RNA.
AB  - The Antwerp database on small ribosomal subunit RNA now offers more than 6000
      nucleotide sequences (August 1996). All these sequences are stored in the form of
      an alignment based on the adopted secondary structure model, which is
      corroborated by the observation of compensating substitutions in the alignment.
      Besides the primary and secondary structure information, literature references,
      accession numbers and detailed taxonomic information are also compiled. For ease
      of use, the complete database is made available to the scientific community via
      World Wide Web at URL http://rrna.uia.ac.be/ssu/ .

PMID- 9016517
TI  - Database on the structure of large ribosomal subunit RNA.
AB  - The latest release of the large ribosomal subunit RNA database contains 429
      sequences. All these sequences are aligned, and incorporate secondary structure
      information. The rRNA WWW Server at URL http://rrna.uia.ac.be/ provides
      researchers with an easily accessible resource to obtain the data in this
      database in a number of computer-readable formats. A new query interface has been
      added to the server. If necessary, the data can also be obtained by anonymous ftp
      from the same site.

PMID- 9016518
TI  - Update of the viroid and viroid-like sequence database: addition of a hepatitis
      delta virus RNA section.
AB  - Recently, we developed and made available an online database that includes all
      the reported (to our knowledge) viroid and viroid-like RNA sequences [Bussire,F.,
      Lafontaine,D. and Perreault,J.-P. (1996)Nucleic Acids Res.24, 1793-1798]. We
      report here an update of this catalogue which includes the addition of a new
      section devoted to human hepatitis delta virus (vHDV) sequences. This new section
      comprises all available vHDV sequences, irrespective of their completeness, which
      have been either published or were available from nucleic acid libraries.
      Additional structural characteristics of the vHDV genome, such as the positions
      of the self-catalytic domains, the antigen open reading frames, etc., are also
      included. The catalogue is available on the World Wide Web (see text) in a user
      friendly form. It should provide an excellent reference point for further
      molecular studies of these small circular pathogenic RNAs.

PMID- 9016519
TI  - The RNA modification database.
AB  - The RNA modification database provides a comprehensive listing of
      posttranscriptionally modified nucleosides from all RNAs, and is maintained as an
      updated version of the initial printed report [Limbach,P.A., Crain,P.F. and
      McCloskey,J.A. (1994)Nucleic Acids Res. , 22, 2183-2196]. Information provided
      for each nucleoside includes: the RNA in which it occurs and phylogenetic
      distribution; common chemical name and symbol; Chemical Abstracts registry number
      and index name; chemical structure; initial literature citations for structural
      characterization or occurrence, and for chemical synthesis. The data are
      available through the WWW and via anonymous ftp.

PMID- 9016520
TI  - The Factor VIII Mutation Database on the World Wide Web: the haemophilia A
      mutation, search, test and resource site. HAMSTeRS update (version 3.0).
AB  - The HAMSTeRS WWW site was set up in 1996 in order to facilitate easy access to,
      and aid understanding of, the causes of haemophilia A at the molecular level;
      previously, the first and second text editions of the database have been
      published in Nucleic Acids Research. This report describes the facilities
      originally available at the site and the recent additions which we have made to
      increase its usefulness to clinicians, the molecular genetics community and
      structural biologists interested in factor VIII. The database (version 3.0) has
      been completely updated with easy submission of point mutations, deletions and
      insertions via e-mail of custom-designed forms. The searching of point mutations
      in the database has been made simpler and more robust, with a concomitantly
      expanded real-time bioinformatic analysis of the database. A methods section
      devoted to mutation detection has been added, highlighting issues such as choice
      of technique and PCR primer sequences. Finally, a FVIII structure section gives
      access to 3D VRML (Virtual Reality Modelling Language) files for any user
      definable residue in a FVIII A domain homology model based on the crystal
      structure of human caeruloplasmin, together with secondary structural data and a
      sound+video animation of the model. It is intended that the general availability
      of this model will assist both in interpretation of causative mutations and
      selection of candidate residues forin vitromutagenesis. The HAMSTeRS URL is
      http://europium.mrc.rpms.ac.uk.

PMID- 9016521
TI  - Haemophilia B: database of point mutations and short additions and deletions, 7th
      edition.
AB  - The seventh edition of the haemophilia B database lists in easily accessible form
      all known factor IX mutations due to small changes (base substitutions and short
      additions and/or deletions of <30 bp) identified in haemophilia B patients. The
      1535 patient entries are ordered by the nucleotide number of their mutation.
      Where known, details are given on: factor IX activity, factor IX antigen in
      circulation, presence of inhibitor and origin of mutation. References to
      published mutations are given and the laboratories generating the data are
      indicated.

PMID- 9016523
TI  - p53 and APC gene mutations: software and databases.
AB  - A large number of different mutations in the APC and p53 tumor suppressor genes
      have been identified in various types of cancer. This substantial increase since
      our previous reports can enable analyses which were not previously possible. In
      order to capture all these new data, the software permitting analysis has been
      improved. This report describes the various improvements since the second release
      of the database.

PMID- 9016522
TI  - Databases and software for the analysis of mutations in the human p53 gene, the
      human hprt gene and both the lacI and lacZ gene in transgenic rodents.
AB  - We have created databases and software applications for the analysis of DNA
      mutations at the humanp53gene, the humanhprtgene and both the rodent
      transgeniclacIandlacZlocus. The databases themselves are stand-alone dBASE files
      and the software for analysis of the databases runs on IBM-compatible computers.
      Each database has a separate software analysis program. The software created for
      these databases permit the filtering, ordering, report generation and display of
      information in the database. In addition, a significant number of routines have
      been developed for the analysis of single base substitutions. One method of
      obtaining the databases and software is via the World Wide Web (WWW). Open the
      following home page with a Web Browser: http://sunsite.unc.edu/dnam/mainpage.ht
      ml . Alternatively, the databases and programs are available via public FTP from:
      anonymous@sunsite.unc.edu . There is no password required to enter the system.
      The databases and software are found beneath the subdirectory:
      pub/academic/biology/dna-mutations. Two other programs are available at the site
      a program for comparison of mutational spectra and a program for entry of
      mutational data into a relational database.

PMID- 9016524
TI  - The PAH mutation analysis consortium database: update 1996.
AB  - A website (http://www.mcgill.ca/pahdb ) is maintained by the curators for a
      Consortium (88 investigators, 28 countries) and all other users; it serves a
      relational database for human locus-specific genetic variation in a defined DNA
      sequence (GenBank U49897); (100 kb on human chromosome 12q24.1, gene symbol PAH).
      The intragenic nucleotide variation is both rare (Q< 0.01), extensive (>320
      different mutations) and phenotype modifying, causing hyperphenylalaninemia by
      impairing phenylalanine hydroxylase function (see OMIM 261600), as well as
      polymorphic and neutral, the latter providing informative locus-specific
      haplotypes (>1200 different mutation/haplotype associations). The PAH database
      contains both offline core components (mutations, population associations and
      data source information) and several accessory online components: (i) relative
      frequencies of mutations by populations/regions (expanding file); (ii) data on
      genotype- phenotype correlations both in vitro and in vivo (new file); (iii)
      polymorphic haplotype structures (new file); (iv) intron sequence data (new file
      for design of primers); (v) description of mouse homologues (new file for
      mutations and phenotypes); (vi) the predicted PAH gene mutability profile
      (improved graphic); (vii) a clinical field for patient use (new interface with
      database). The website home page has been revised and a counter is recording >15
      visits per day. Linkages to other mutation databases and an alliance of mutation
      database curators (new) are expanding. The primary 'electronic publication'
      reports now vastly exceed print reports. PAHdb serves as a prototype for
      obtaining, storing and distributing records of human genetic variation.

PMID- 9016525
TI  - The alpha/beta fold family of proteins database and the cholinesterase gene
      server ESTHER.
AB  - ESTHER (for esterases, alpha/betahydrolase enzyme and relatives) is a database of
      sequences phylogenetically related to cholinesterases. These sequences define a
      homogeneous group of enzymes (carboxylesterases, lipases and hormone-sensitive
      lipases) sharing a similar structure of a central beta-sheet surrounded by alpha
      helices. Among these proteins a wide range of functions can be found (hydrolases,
      adhesion molecules, hormone precursors). The purpose of ESTHER is to help
      comparison of structures and functions of members of the family. Since the last
      release, new features have been added to the server. A BLAST comparison tool
      allows sequence homology searches within the database sequences. New sections are
      available: kinetics and inhibitors of cholinesterases, fasciculin
      acetylcholinesterase interaction and a gene structure review. The mutation
      analysis compilation has been improved with three-dimensional images. A mailing
      list has been created.

PMID- 9016527
TI  - Database of p53 gene somatic mutations in human tumors and cell lines: updated
      compilation and future prospects.
AB  - In recent years, there has been an exponential increase in the number of p53
      mutations identified in human cancers. The p53 mutation database consists of a
      list of point mutations in thep53 gene of human tumors and cell lines, compiled
      from the published literature and made available through electronic media. The
      database is now maintained at the International Agency for Research on Cancer
      (IARC) and is updated twice a year. The current version contains records on 5091
      published mutations and is expected to surpass the 6000 mark in the January 1997
      release. The database is available in various formats through the European
      Bioinformatics Institute (EBI) ftp server at:
      ftp://ftp.ebi.ac.uk/pub/databases/p53/ or by request from IARC
      (p53database@iarc.fr) and will be searchable through the SRS system in the near
      future. This report provides a description of the criteria for inclusion of data
      and of the current formats, a summary of the relevance ofp53 mutation analysis to
      clinical and biological questions, and a brief discussion of the prospects for
      future developments.

PMID- 9016526
TI  - Marfan Database (second edition): software and database for the analysis of
      mutations in the human FBN1 gene.
AB  - Fibrillin is the major component of extracellular microfibrils. Mutations in the
      fibrillin gene on chromosome 15 (FBN1) were described at first in the heritable
      connective tissue disorder, Marfan syndrome (MFS). More recently, FBN1 has also
      been shown to harbor mutations related to a spectrum of conditions phenotypically
      related to MFS. These mutations are private, essentially missense, generally non
      recurrent and widely distributed throughout the gene. To date no clear
      genotype/phenotype relationship has been observed excepted for the localization
      of neonatal mutations in a cluster between exons 24 and 32. The second version of
      the computerized Marfan database contains 89 entries. The software has been
      modified to accomodate new functions and routines.

PMID- 9016528
TI  - The androgen receptor gene mutations database.
AB  - The current version of the androgen receptor (AR) gene mutations database is
      described. The total number of reported mutations has risen from 212 to 272. We
      have expanded the database: (i) by adding a large amount of new data on somatic
      mutations in prostatic cancer tissue; (ii) by defining a new constitutional
      phenotype, mild androgen insensitivity (MAI); (iii) by placing additional
      relevant information on an internet site (http://www.mcgill.ca/androgendb/ ). The
      database has allowed us to examine the contribution of CpG sites to the
      multiplicity of reports of the same mutation in different families. The database
      is also available from EMBL (ftp.ebi.ac.uk/pub/databases/androgen) or as a
      Macintosh Filemaker Pro or Word file (MC33@musica,mcgill.ca)

PMID- 9016529
TI  - The Nuclear Receptor Resource Project.
AB  - We have expanded the original Glucocorticoid Receptor Resource (GRR) database to
      include several individual resources as part of a larger project called the
      Nuclear Receptor Resource (NRR). In addition to the GRR, the NRR currently
      features the Thyroid Hormone Receptor Resource, the Androgen Receptor Resource,
      the Mineralocorticoid Receptor Resource, the Vitamin D Receptor Resource, and the
      Steroid Receptor Associated Proteins Resource. The goal of the NRR project is to
      provide a comprehensive resource for information on the nuclear receptor
      superfamily, and to provide a forum for the dissemination and discussion of both
      published and unpublished material on these proteins. Although the individual
      resources are managed from different servers, all the files are integrated and
      can be accessed through the project's Home Page, housed at http://nrr.
      georgetown.edu/nrr.html. In the near future, we hope to expand the project to
      contain information on other nuclear receptors and to better our electronic
      publication system. To accomplish this, we encourage the involvement of nuclear
      receptor investigators in the NRR.

PMID- 9016530
TI  - BTKbase, mutation database for X-linked agammaglobulinemia (XLA)
AB  - X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in
      the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK). A database
      (BTKbase) of BTK mutations has been compiled and the recent update lists 368
      entries from 318 unrelated families showing 228 unique molecular events. In
      addition to mutations the database lists also some polymorphisms and site
      directed mutations. Each patient is given a unique patient identity number (PIN).
      Information is provided regarding the phenotype including symptoms. Mutations in
      all the five domains of BTK have been noticed to cause the disease, the most
      common event being missense mutations. The mutations appear almost uniformly
      throughout the molecule and frequently affect CpG sites forming arginine
      residues. These hot spots have generally pyrimidines 5'and purines 3'to the
      mutated cytosine. A decreased frequency of missense mutations was found in the
      TH, SH3 and the upper lobe of the kinase domain. The putative structural
      implications of all the missense mutations are given in the database showing 228
      unique molecular events, including a novel missense mutation causing an R28C
      substitution as previously seen in the Xid mouse.

PMID- 9016532
TI  - The human type I collagen mutation database.
AB  - Type I collagen is the most abundant and ubiquitously distributed of the collagen
      family of proteins. It is a heterotrimer comprising two alpha1(I) chains and one
      alpha2(I) chain which are encoded by the unlinked loci COL1A1 and COL1A2
      respectively. Mutations at these loci result primarily in the connective tissue
      disorders osteogenesis imperfecta and Ehlers-Danlos syndrome types VIIA and VIIB.
      Two instances of osteoporosis and a single instance of Marfan syndrome are also
      the result of mutations at these loci. The mutation data are accessible on the
      world wide web at http://www.le.ac.uk/depts/ge/collagen/collagen.html

PMID- 9016533
TI  - Expansion of the 16S and 23S ribosomal RNA mutation databases (16SMDB and
      23SMDB).
AB  - The Ribosomal RNA Mutation Databases (16SMDB and 23SMDB) provide lists of mutated
      positions in 16S and 23S ribosomal RNA from Escherichia coli and the identity of
      each alteration. Information provided for each mutation includes: (i) a brief
      description of the phenotype(s) associated with each mutation; (ii) whether a
      mutant phenotype has been detected by in vivo or in vitro methods; and (iii)
      relevant literature citations. The databases are available via ftp and on the
      World Wide Web. Expansion of the databases to include information about mutations
      isolated in organisms other than E.coli is currently in progress.

PMID- 9016534
TI  - A mutation spectra database for bacterial and mammalian genes.
AB  - Each mutation spectrum in this database is a dataset of changes in DNA base
      sequence in mutations induced in a gene by a particular mutagen (including
      spontaneous processes) under defined conditions. There are 240 datasets with 24
      500 mutants in nine bacterial genes, two phage genes, five mammalian genes and
      one yeast gene. The database is available on the Web at
      http://info.med.yale.edu/mutbase/ . The data tables can be viewed on the Web and
      downloaded in text form for local use. The data are also available in dBASE III,
      a format which can be utilized by essentially any desktop computer database
      program or spreadsheet, and makes feasible analyses of a large number of mutants.
      Researchers are invited to submit additional data. A data entry program, MUTSIN,
      diagrams each mutation on the computer screen as the data are entered and alerts
      the user to any discrepancies between the entry and the gene sequence.

PMID- 9016531
TI  - Software and database for the analysis of mutations in the human LDL receptor
      gene.
AB  - The low-density lipoprotein receptor (LDLr) plays a pivotal role in cholesterol
      homeostasis. Mutations in the LDLr gene (LDLR), which is located on chromosome
      19, cause familial hypercholesterolemia (FH), an autosomal dominant disorder
      characterized by severe hypercholesterolemia associated with premature coronary
      atherosclerosis. To date almost 300 mutations have been identified in the LDLR
      gene. To facilitate the mutational analysis of the LDLR gene, and promote the
      analysis of the relationship between genotype and phenotype, a software package
      along with a computerized database (currently listing 210 entries) have been
      created.

PMID- 9016535
TI  - MITOMAP: an update on the status of the human mitochondrial genome database.
AB  - We have continued to develop MITOMAP, a comprehensive database for the human
      mitochondrial DNA (mtDNA). MITOMAP uses the mtDNA sequence as the unifying
      element for bringing together information on mitochondrial genome structure and
      function, pathogenic mutations and their clinical characteristics, population
      associated variation and gene-gene interactions. As increasingly larger regions
      of the human genome are sequenced and characterized, the need for integrating
      such information will grow. Consequently, MITOMAP not only provides a valuable
      reference for the mitochondrial biologist, it will also provide a model for the
      development of comprehensive, multi-media information storage and retrieval
      systems for other components of the human genome. This paper is an update of the
      changes which have occurred to MITOMAP over the past year.

PMID- 9016536
TI  - MmtDB: a Metazoa mitochondrial DNA variants database.
AB  - The present paper describes the structure of MmtDB-a specialized database
      designed to collect Metazoa mitochondrial DNA variants. Priority in the data
      collection is given to the Metazoa species for which a large amount of variants
      is available, as it is the case for human variants. Starting from the sequences
      available in the Nucleotide Sequence Databases, the redundant sequences are
      removed and new sequences from other sources are added. Value-added information
      are associated to each variant sequence, e.g. analysed region, experimental
      method, tissue and cell lines, population data, sex, age, family code and
      information about the variation events (nucleotide position, involved gene,
      restriction site's gain or loss). Cross-references are introduced to the EMBL
      Data Library, as well as an internal cross-referencing among MmtDB entries
      according to their tissual, heteroplasmic, familiar and aplotypical correlation.
      MmtDB can be accessed through the World Wide Web at URL [see text].

PMID- 9016537
TI  - IMGT, the international ImMunoGeneTics database.
AB  - IMGT, the international ImMunoGeneTics database, is an integrated database
      specializing in immunoglobulins, T-cell receptors (TcR) and major
      histocompatibility complex (MHC) of all vertebrate species, initiated and co
      ordinated by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier,
      France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes two databases: LIGM-DB (for
      immunoglobulins and TcR) and MHC/HLA-DB. IMGT comprises expertly annotated
      sequences and alignment tables. LIGM-DB contains more than 19 000 immunoglobulin
      and TcR sequences from 78 species. MHC/HLA-DB contains class I and class II human
      leukocyte antigen alignment tables. An IMGT tool, DNAPLOT, developed for
      immunoglobulins, TcR and MHC sequence alignments, is also available. IMGT works
      in close collaboration with the EMBL database. IMGT goals are to establish a
      common data access to all immunogenetics data, including sequences,
      oligonucleotide primers, gene maps and other genetic data of immunoglobulins, TcR
      and MHC molecules, and to provide a graphical user-friendly data access. IMGT
      will have important implications in medical research (repertoire in autoimmune
      diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody
      engineering), genome diversity and genome evolution studies. IMGT can be accessed
      at http://imgt.cnusc.fr:8104 and http://www.ebi.ac.uk/IMGT

PMID- 9016538
TI  - Novel developments with the PRINTS protein fingerprint database.
AB  - The PRINTS database of protein family 'fingerprints' is a diagnostic resource
      that complements the PROSITE dictionary of sites and patterns. Unlike regular
      expressions, fingerprints exploit groups of conserved motifs within sequence
      alignments to build characteristic signatures of family membership. Thus
      fingerprints inherently offer improved diagnostic reliability by virtue of the
      mutual context provided by motif neighbours. To date, 600 fingerprints have been
      constructed and stored in PRINTS, representing a 50% increase in the size of the
      database in the last year. The current version, 13.0, encodes approximately 3000
      motifs, covering a range of globular and membrane proteins, modular polypeptides,
      and so on. The database is accessible via UCL's Bioinformatics World Wide Web
      (WWW) server at http://www.biochem.ucl.ac.uk/bsm/dbbrowser / . We describe here
      progress with the database, its Web interface, and a recent exciting development:
      the integration of a novel colour alignment editor
      (http://www.biochem.ucl.ac.uk/bsm/dbbrowser++  +/CINEMA ), which allows
      visualisation and interactive manipulation of PRINTS alignments over the
      Internet.

PMID- 9016539
TI  - The PROSITE database, its status in 1997.
AB  - The PROSITE database consists of biologically significant patterns and profiles
      formulated in such a way that with appropriate computational tools it can help to
      determine to which known family of protein (if any) a new sequence belongs, or
      which known domain(s) it contains.

PMID- 9016540
TI  - Recent enhancements to the Blocks Database servers.
AB  - The Blocks Database contains multiple alignments of conserved regions in protein
      families which can be searched by e-mail (blocks@blocks.fhcrc.org) and World Wide
      Web (http://blocks.fhcrc.org/ ) servers to classify protein and nucleotide
      sequences. Recent enhancements to the servers include: (i) improved calculation
      of position-specific scoring matrices from blocks; (ii) availability of the
      Prints protein fingerprint database for searching in Blocks format; (iii) a
      representative sequence biased towards the Blocks of a protein family; (iv) a
      tree constructed from the Blocks of a protein family; (v) links to related World
      Wide Web pages for a family; and (vi) the new Local Alignment of Multiple
      Alignments (LAMA) method to search a block against a database of blocks.

PMID- 9016541
TI  - The HSSP database of protein structure-sequence alignments.
AB  - HSSP is a derived database merging structural (3-D) and sequence (1-D)
      information. For each protein of known 3-D structure from the Protein Data Bank
      (PDB), the database has a multiple sequence alignment of all available homologues
      and a sequence profile characteristic of the family. The list of homologues is
      the result of a database search in SwissProt using a position-weighted dynamic
      programming method for sequence profile alignment (MaxHom). The database is
      updated frequently. The listed homologues are very likely to have the same 3-D
      structure as the PDB protein to which they have been aligned. As a result, the
      database is not only a database of aligned sequence families, but also a database
      of implied secondary and tertiary structures covering 29% of all SwissProt-stored
      sequences.

PMID- 9016542
TI  - Dali/FSSP classification of three-dimensional protein folds.
AB  - The FSSP database presents a continuously updated structural classification of
      three-dimensional protein folds. It is derived using an automatic structure
      comparison program (Dali) for the all-against-all comparison of over 6000 three
      dimensional coordinate sets in the Protein Data Bank (PDB). Sequence-related
      protein families are covered by a representative set of 813 protein chains.
      Hierachical clustering based on structural similarities yields a fold tree that
      defines 253 fold classes. For each representative protein chain, there is a
      database entry containing structure-structure alignments with its structural
      neighbours in the PDB. The database is accessible online through World Wide Web
      browsers and by anonymous ftp (file transfer protocol). The overview of fold
      space and the individual data sets provide a rich source of information for the
      study of both divergent and convergent aspects of molecular evolution, and define
      useful test sets and a standard of truth for assessing the correctness of
      sequence-sequence or sequence-structure alignments.

PMID- 9016543
TI  - An update of the DEF database of protein fold class predictions.
AB  - An update is given on the Database of Expected Fold classes (DEF) that contains a
      collection of fold-class predictions made from protein sequences and a mail
      server that provides new predictions for new sequences. To any given sequence one
      of 49 fold-classes is chosen to classify the structure related to the sequence
      with high accuracy. The updated prediction system is developed using data from
      the new version of the 3D-ALI database of aligned protein structures and thus is
      giving more reliable and more detailed predictions than the previous DEF system.

PMID- 9016544
TI  - SCOP: a structural classification of proteins database.
AB  - The Structural Classification of Proteins (SCOP) database provides a detailed and
      comprehensive description of the relationships of all known proteins structures.
      The classification is on hierarchical levels: the first two levels, family and
      superfamily, describe near and far evolutionary relationships; the third, fold,
      describes geometrical relationships. The distinction between evolutionary
      relationships and those that arise from the physics and chemistry of proteins is
      a feature that is unique to this database, so far. SCOP also provides for each
      structure links to atomic co-ordinates, images of the structures, interactive
      viewers, sequence data, data on any conformational changes related to function
      and literature references. The database is freely accessible on the World Wide
      Web (WWW) with an entry point at URL http://scop.mrc-lmb.cam.ac.uk/scop/

PMID- 9016546
TI  - Codon usage tabulated from the international DNA sequence databases.
AB  - The codon usage in individual protein genes has been calculated using the
      nucleotide sequence obtained from the GenBank Genetic Sequence Database. Sum of
      the codon use of each organism has been also calculated. The data files can be
      obtained from anonymous ftp sites of DDBJ, DISC and EBI. The list of codon usage
      of genes in organisms was made searchable by name of organism through a web site.
      The compilation has been synchronized with a major release of GenBank.

PMID- 9016545
TI  - The SBASE protein domain library, release 5.0: a collection of annotated protein
      sequence segments.
AB  - SBASE 5.0 is the fifth release of SBASE, a collection of annotated protein domain
      sequences that represent various structural, functional, ligand-binding and
      topogenic segments of proteins. SBASE was designed to facilitate the detection of
      functional homologies and can be searched with standard database-search programs.
      The present release contains over 79863 entries provided with standardized names
      and is cross-referenced to all major sequence databases and sequence pattern
      collections. The information is assigned to individual domains rather than to
      entire protein sequences, thus SBASE contains substantially more cross-references
      and links than do the protein sequence databases. The entries are clustered into
      >16 000 groups in order to facilitate the detection of distant similarities.
      SBASE 5.0 is freely available by anonymous 'ftp' file transfer from
      <ftp.icgeb.trieste.it >. Automated searching of SBASE with BLAST can be carried
      out with the WWW-server <http://www.icgeb.trieste.it/sbase/ >. and with the
      electronic mail server <sbase@icgeb.trieste.it >which now also provides a graphic
      representation of the homologies. A related WWW-server
      <http://www.abc.hu/blast.html > and e-mail server <domain@hubi.abc.hu > predicts
      SBASE domain homologies on the basis of SWISS-PROT searches.

PMID- 9016548
TI  - REBASE-restriction enzymes and methylases.
AB  - REBASE is a comprehensive database of information about restriction enzymes and
      their associated methylases, including their recognition and cleavage sites and
      their commercial availability. Information from REBASE is available via monthly
      electronic mailings as well as via anonymous ftp, WAIS/gopher and through the
      World Wide Web (http://www.neb.com/rebase ). Specialized files are available that
      can be used directly by many software packages.

PMID- 9016547
TI  - The translational signal database, TransTerm: more organisms, complete genomes.
AB  - TransTerm is a database of initiation and termination sequence contexts from more
      than 250 organisms listed in GenBank, including the four complete
      genomes:Haemophilus influenzae, Methanococcus jannaschii, Mycoplasma
      genitalium,and Saccharomyces cerevisiae. For the current release, more than 60
      000 coding sequences were analysed. The tabulated data include initiation and
      termination contexts organised by species along with quantitative parameters
      about individual coding sequences (length, %GC, GC3, Nc and CAI). There are also
      tables of initiation- and termination-region nucleotide-frequencies, codon usage
      tables and summaries of stop signal usage. TransTerm is available on the World
      Wide Web at: http://biochem.otago.ac.nz:800/Transterm/homepage.h tml

PMID- 9016550
TI  - TRANSFAC, TRRD and COMPEL: towards a federated database system on transcriptional
      regulation.
AB  - Three databases that provide data on transcriptional regulation are described.
      TRANSFAC is a database on transcription factors and their DNA binding sites. TRRD
      (Transcription Regulatory Region Database) collects information about complete
      regulatory regions, their regulation properties and architecture. COMPEL
      comprises specific information on composite regulatory elements. Here, we
      describe the present status of these databases and the first steps towards their
      federation.

PMID- 9016549
TI  - The ribonuclease P database.
AB  - Ribonuclease P is responsible for the removal of leader sequences from tRNA
      precursors. Ribonuclease P is a ribonucleoprotein, and in bacteria the RNA
      subunit alone is catalytically active in vitro, i.e. it is a ribozyme. The
      Ribonuclease P Database is a compilation of ribonuclease P sequences, sequence
      alignments, secondary structures, three-dimensional models, and accessory
      information, available via the World Wide Web.

PMID- 9016551
TI  - MHCPEP, a database of MHC-binding peptides: update 1996.
AB  - MHCPEP is a curated database comprising over 9000 peptide sequences known to bind
      MHC molecules. Entries are compiled from published reports as well as from direct
      submissions of experimental data. Each entry contains the peptide sequence, its
      MHC specificity and, when available, experimental method, observed activity,
      binding affinity, source protein, anchor positions and publication references.
      The present format of the database allows text string matching searches but can
      easily be converted for use in conjunction with sequence analysis packages. The
      database can be accessed via Internet using WWW, FTP or Gopher.

PMID- 9016552
TI  - Histone and histone fold sequences and structures: a database.
AB  - A database of aligned histone protein sequences has been constructed based on the
      results of homology searches of the major public sequence databases. In addition,
      sequences of proteins identified as containing the histone fold motif and
      structures of all known histone and histone fold proteins have been included in
      the current release. Database resources include information on conflicts between
      similar sequence entries in different source databases, multiple sequence
      alignments, and links to the Entrez integrated information retrieval system at
      the National Center for Biotechnology Information (NCBI). The database currently
      contains over 1000 protein sequences. All sequences and alignments in this
      database are available through the World Wide Web at: http:
      //www.ncbi.nlm.nih.gov/Baxevani/HISTONES/ .

PMID- 9016553
TI  - The directory of P450-containing systems in 1996.
AB  - The Directory of P450-containing Systems on WorldWide Web has been designed to
      facilitate access to electronic resources for all researchers working in the
      field of P450-containing and related enzyme systems. Currently, it contains the
      most up-to-date list of sequences of both the P450 superfamily and proteins
      mediating electron transfer to P450, i.e. NADPH:P450 reductases, specific
      NAD(P)H:ferredoxin reductases, cytochromeb5 reductases, ferredoxins and
      cytochromesb5, and their homologues. All the referenced sequences are provided
      with accession numbers and links to major sequence databanks: PIR, SWISS-PROT,
      EMBL/GenBank and PRF. An associated database of steroid substrates and products
      of P450-dependent reactions has also been developed.

PMID- 9016554
TI  - O-GLYCBASE version 2.0: a revised database of O-glycosylated proteins.
AB  - O-GLYCBASE is an updated database of information on glycoproteins and their O
      linked glycosylation sites. Entries are compiled and revised from the literature,
      and from the SWISS-PROT database. Entries include information about species,
      sequence, glycosylation sites and glycan type. O-GLYCBASE is now fully cross
      referenced to the SWISS-PROT, PIR, PROSITE, PDB, EMBL, HSSP, LISTA and MIM
      databases. Compared with version 1.0 the number of entries have increased by 34%.
      Revision of the O-glycan assignment was performed on 20% of the entries. Sequence
      logos displaying the acceptor specificity patterns for the GalNAc, mannose and
      GlcNAc transferases are shown. The O-GLYCBASE database is available through WWW
      or by anonymous FTP.

PMID- 9016555
TI  - Neither HMG-14a nor HMG-17 gene function is required for growth of chicken DT40
      cells or maintenance of DNaseI-hypersensitive sites.
AB  - HMG-14 and HMG-17 form a family of ubiquitous non-histone chromosomal proteins
      and have been reported to bind preferentially to regions of active chromatin
      structure. Our previous studies demonstrated that the chicken HMG-17 gene is
      dispensable for normal growth of the DT40 chicken lymphoid cell line. Here it is
      shown that the major chicken HMG-14 gene,HMG-14a, is also dispensable and,
      moreover, that DT40-derived cells lacking both HMG-17 and HMG-14a proteins show
      no obvious change in phenotype with respect to the parental DT40 cells.
      Furthermore, no compensatory changes in HMG-14b or histone protein levels were
      observed in cells lacking both HMG-14a and HMG-17, nor were any alterations
      detected in such hallmarks of chromatin structure as DNaseI-hypersensitive sites
      or micrococcal nuclease digestion patterns. It is concluded that the HMG-14a and
      HMG-17 proteins are not required for normal growth of avian cell linesin vitro,
      nor for the maintenance of DNaseI-hypersensitive sites in chromatin.

PMID- 9016556
TI  - Regulation of DNA metabolic enzymes upon induction of preB cell development and
      V(D)J recombination: up-regulation of DNA polymerase delta.
AB  - Withdrawal of interleukin-7 from cultured murine preB lymphocytes induces cell
      differentiation including V(D)J immunoglobulin gene rearrangements and cell cycle
      arrest. Advanced steps of the V(D)J recombination reaction involve processing of
      coding ends by several largely unidentified DNA metabolic enzymes. We have
      analyzed expression and activity of DNA polymerases alpha, beta, delta and
      epsilon, proliferating cell nuclear antigen (PCNA), topoisomerases I and II,
      terminal deoxynucleotidyl transferase (TdT) and DNA ligases I, III and IV upon
      induction of preB cell differentiation. Despite the immediate arrest of cell
      proliferation, DNA polymerase delta protein levels remained unchanged for
      approximately 2 days and its activity was up-regulated several-fold, while PCNA
      was continuously present. Activity of DNA polymerases alpha,beta and epsilon
      decreased. Expression and activity of DNA ligase I were drastically reduced,
      while those of DNA ligases III and IV remained virtually constant. No changes in
      DNA topoisomerases I or II expression and activity occurred and TdT expression
      was moderately increased early after induction. Our results render DNA polymerase
      delta a likely candidate acting in DNA synthesis related to V(D)J recombination
      in lymphocytes.

PMID- 9016557
TI  - The SV40 large T-antigen helicase can unwind four stranded DNA structures linked
      by G-quartets.
AB  - We describe a novel activity of the SV40 large T-ag helicase, the unwinding of
      four stranded DNA structures linked by stacked G-quartets, namely stacked groups
      of four guanine bases bound by Hoogsteen hydrogen bonds. The structures unwound
      by the helicase were of two types: (i) quadruplexes comprising four parallel
      strands that were generated by annealing oligonucleotides including clustered G
      residues in a buffer containing Na+ions. Each parallel quadruplex consisted of
      four oligonucleotide molecules. (ii) Complexes comprising two parallel and two
      antiparallel strands that were generated by annealing the above oligonucleotides
      in a buffer containing K+ions. Each antiparallel complex consisted of two folded
      oligonucleotide molecules. Unwinding of these unusual DNA structures by the T-ag
      was monitored by gel electrophoresis. The unwinding process required ATP and at
      least one single stranded 3'-tail extending beyond the four stranded region.
      These data indicated that the T-ag first binds the 3'-tail and moves in a 3'-
      >5'direction, using energy provided by ATP hydrolysis; then it unwinds the four
      stranded DNA into single strands. This helicase activity may affect processes
      such as recombination and telomere extension, in which four stranded DNA could
      play a role.

PMID- 9016558
TI  - Substitution and deletion mutations induced by 2-hydroxyadenine in Escherichia
      coli: effects of sequence contexts in leading and lagging strands.
AB  - To evaluate the mutation frequency and the mutation spectrum of 2-hydroxyadenine
      (2-OH-Ade), an oxidative DNA lesion, the modified base was site-specifically
      incorporated into a unique restriction enzyme site (SalI, GTCGA*C or AflII,
      CTTA*AG where A* represents 2-OH-Ade) in single- and double-stranded vectors. The
      2-OH-Ade residues were introduced into (+)- and (-)-strands of the double
      stranded vectors and into the (+)-strand of single-stranded vectors. When the
      vectors were transfected intoEscherichia coli, the modified base showed little to
      no cytotoxicity. The mutation frequencies of 2-OH-Ade in the SalI and AflII sites
      were approximately 0.8 and 0.07%, respectively, with double-stranded (+)-vectors.
      An increase in the mutation frequencies was not observed with single-stranded
      vectors. When incorporated into the (-)-strand, the mutation frequencies of 2-OH
      Ade in the SalI and AflII sites were approximately 0.3 and 0.1%, respectively.
      The mutations observed most frequently were -1 deletions at both positions, in
      the case of the (+)-strand. On the other hand, we observed that 2-OH-Ade in the (
      )-strand induced A-->G and A-->T substitutions. These results indicate that 2-OH
      Ade residues in DNA induce substitution and deletion mutations without blocking
      replication inE.coli.

PMID- 9016559
TI  - Cell-type specific DNA-protein interactions at the tissue-type plasminogen
      activator promoter in human endothelial and HeLa cells in vivo and in vitro.
AB  - Tissue-type plasminogen activator (t-PA) gene expression in human endothelial
      cells and HeLa cells is stimulated by the protein kinase C activator phorbol 12
      myristate 13-acetate (PMA) at the level of transcription. To study the mechanism
      of transcriptional regulation, we have characterized a segment of the t-PA gene
      extending from -135 to +100 by in vivo footprinting analysis [dimethyl sulphate
      (DMS) method] and gel mobility shift assay. In vivo footprinting analysis
      revealed changes in cleavage pattern in five distinct promoter elements in both
      endothelial cells and HeLa cells, including a PMA-responsive element (TRE), a
      CTF/NF-1 binding site and three GC-boxes, and an altered cleavage pattern of the
      TRE and CTF/NF-1 element after PMA treatment of HeLa cells. Although endothelial
      cells and HeLa cells differed in the exact G residues protected by nuclear
      proteins,in vitro bandshift analysis showed that nuclear protein binding to the t
      PA promoter was qualitatively and quantitatively very similar in both cell types,
      except for the TRE. Protein binding to the TRE under non- stimulated conditions
      was much higher in human endothelial cells than in HeLa cells, and this TRE-bound
      protein showed a lower dissociation rate in the endothelial cells than in HeLa
      cells. In endothelial cells, the proteins bound to the TRE consisted mainly of
      the AP-1 family members JunD and Fra-2, while in HeLa cells predominantly JunD,
      FosB and Fra-2 were bound. The proteins bound to the other protected promoter
      elements were identified as SP-1 (GC-box II and III) and CTF/NF-1 (CTF/NF-1
      binding site). After PMA treatment of the cells, AP-1 and SP-1 binding was
      increased two-fold in endothelial cell nuclear extracts and >20-fold in HeLa
      nuclear extracts. In the endothelial cells, all Jun and Fos forms (c-Jun, JunB,
      JunD, c-Fos, FosB, Fra-1 and Fra-2) were part of the AP-1 complex after PMA
      induction. In HeLa cells, the complex consisted predominantly of c-Jun and the
      Fos family members FosB and Fra-2. In the light of previous studies involving
      mutational analysis of the human and murine t-PA promoter our results underline
      an important role of the five identified promoter regions in basal and PMA
      stimulated t-PA gene expression in intact human endothelial cells and HeLa cells.
      The small differences in DMS protection pattern and differences in the individual
      AP-1 components bound in endothelial cells and HeLa cells point to subtle cell
      type specific differences in t-PA gene regulation.

PMID- 9016561
TI  - Transcription activation at class II CRP-dependent promoters: the role of
      different activating regions.
AB  - Transcription activation by the Escherichia coli cyclic AMP receptor protein
      (CRP) at Class II promoters is dependent on direct interactions between two
      surface-exposed activating regions (AR1 and AR2) and two contact sites in RNA
      polymerase. The effects on transcription activation of disrupting either AR1 or
      AR2 have been measured at different Class II promoters. AR2 but not AR1 is
      essential for activation at all the Class II promoters that were tested. The
      effects of single positive control substitutions in AR1 and AR2 vary from one
      promoter to another: the effects of the different substitutions are contingent on
      the -35 hexamer sequence. Abortive initiation assays have been used to quantify
      the effects of positive control substitutions in each activating region on the
      kinetics of transcription initiation at the Class II CRP- dependent promoter
      pmelRcon. At this promoter, the HL159 substitution in AR1 results in a defect in
      the initial binding of RNA polymerase whilst the KE101 substitution in AR2
      reduces the rate of isomerization from the closed to the open complex.

PMID- 9016562
TI  - Effects of variations in length of hammerhead ribozyme antisense arms upon the
      cleavage of longer RNA substrates.
AB  - The efficacy of intracellular binding of hammerhead ribozyme to its cleavage site
      in target RNA is a major requirement for its use as a therapeutic agent. Such
      efficacy can be influenced by several factors, such as the length of the ribozyme
      antisense arms and mRNA secondary structures. Analysis of various IL-2 hammerhead
      ribozymes having different antisense arms but directed to the same site predicts
      that the hammerhead ribozyme target site is present within a double-stranded
      region that is flanked by single-stranded loops. Extension of the low cleaving
      hammerhead ribozyme antisense arms by nucleotides that base pair with the single
      stranded regions facilitated the hammerhead ribozyme binding to longer RNA
      substrates (e.g. mRNA). In addition, a correlation between the in vitro and
      intracellular results was also found. Thus, the present study would facilitate
      the design of hammerhead ribozymes directed against higher order structured
      sites. Further, it emphasises the importance of detailed structural
      investigations of hammerhead ribozyme full-length target RNAs.

PMID- 9016560
TI  - The SRP9/14 subunit of the human signal recognition particle binds to a variety
      of Alu-like RNAs and with higher affinity than its mouse homolog.
AB  - The heterodimeric subunit, SRP9/14, of the signal recognition particle (SRP) has
      previously been found to bind to scAlu and scB1 RNAs in vitro and to exist in
      large excess over SRP in anthropoid cells. Here we show that human and mouse
      SRP9/14 bind with high affinities to other Alu-like RNAs of different
      evolutionary ages including the neuron-specific BC200 RNA. The relative
      dissociation constants of the different RNA-protein complexes are inversely
      proportional to the evolutionary distance between the Alu RNA species and 7SL
      RNA. In addition, the human SRP9/14 binds with higher affinity than mouse SRP9/14
      to all RNAs analyzed and this difference is not explained by the additional C
      terminal domain present in the anthropoid SRP14. The conservation of high
      affinity interactions between SRP9/14 and Alu-like RNAs strongly indicates that
      these Alu-like RNPs exist in vivo and that they have cellular functions. The
      observation that human SRP9/14 binds better than its mouse counterpart to
      distantly related Alu RNAs, such as recently transposed elements, suggests that
      the anthropoid-specific excess of SRP9/14 may have a role in controlling Alu
      amplification rather than in compensating a defect in SRP assembly and functions.

PMID- 9016564
TI  - Template-directed dye-terminator incorporation (TDI) assay: a homogeneous DNA
      diagnostic method based on fluorescence resonance energy transfer.
AB  - A new method for DNA diagnostics based on template-directed primer extension and
      detection by fluorescence resonance energy transfer is described. In this method,
      amplified genomic DNA fragments containing polymorphic sites are incubated with a
      5'-fluorescein-labeled primer (designed to hybridize to the DNA template adjacent
      to the polymorphic site) in the presence of allelic dye-labeled
      dideoxyribonucleoside triphosphates and a modified Taq DNA polymerase (Klentaq1
      FY). The dye-labeled primer is extended one base by the dye-terminator specific
      for the allele present on the template. At the end of the genotyping reaction,
      the fluorescence intensities of the two dyes in the reaction mixture are analyzed
      directly without separation or purification. This homogeneous DNA diagnostic
      method, which we call the template-directed dye-terminator incorporation assay,
      is shown to be highly sensitive and specific and is suitable for automated
      genotyping of large numbers of samples.

PMID- 9016563
TI  - Distamycin prolongs E-selectin expression by interacting with a specific NF
      kappaB-HMG-I(Y) binding site in the promoter.
AB  - The E-selectin cell adhesion protein plays a critical role in mediating adherence
      of leukocytes to endothelium at sites of inflammation. Cytokine-induced E
      selectin expression on the surface of endothelial cells is transient; mRNA
      expression peaks at 3-4 h after induction and returns to basal levels within 24
      h. The mechanism for this transcriptional down-modulation is not known. Promoter
      binding factors responsible for induced gene expression include NF-kappaB, which
      binds at three sites within the E-selectin promoter, and HMG-I(Y), which binds to
      the A/T-rich core found at the centre of these binding sites. Distamycin is an
      antibiotic that also binds A/T-rich DNA and inhibits HMG-I(Y) DNA binding. To
      study the role of HMG-I(Y) in E-selectin expression, we have examined the effect
      of distamycin on the cytokine-induced E-selectin expression cycle. We found that
      distamycin prolonged E-selectin expression, both by sustaining mRNA transcription
      and by extending the transcript's half-life. The distamycin effect on
      transcription was mediated through one of the three NF-kappaB-HMG-I(Y) binding
      sites (NF-kappaBII) within the promoter. This suggests that the NF-kappaB-HMG
      I(Y) complex interacting at the NF-kappaBII site plays a role not only in
      cytokine induction of E-selectin expression, but also in its down-modulation.

PMID- 9016565
TI  - Association of U2 snRNP with the spliceosomal complex E.
AB  - In metazoans, the E complex is operationally defined as an ATP-independent
      spliceosomal complex that elutes as a single peak on a gel filtration column and
      can be chased into spliced products in the presence of an excess of competitor
      pre-mRNA. The A complex is the first ATP-dependent functional spliceosomal
      complex. U1 snRNP first binds tightly to the 5'splice site in the E complex and
      U2 snRNP first binds tightly to the branch site in the A complex. In this study,
      we have generated and characterized a monoclonal antibody (mAb 4G8) directed
      against SAP 62, a component of U2 snRNP and a subunit of the essential mammalian
      splicing factor SF3a. We show that this antibody is highly specific for SAP 62,
      detecting only SAP 62 on Western blots and immunoprecipitating only SAP 62 from
      nuclear extracts. The anti-SAP 62 antibody also immunoprecipitates U2 snRNP and
      the A complex. Significantly, however, we find that the E complex is also
      efficiently immunoprecipitated by the anti-SAP 62 antibody. This antibody does
      not cross-react with any E complex-specific components, indicating that SAP 62
      itself is associated with the E complex. To determine whether other U2 snRNP
      components are associated with the E complex, we used antibodies to the U2 snRNP
      proteins B"and SAP 155. These antibodies also specifically immunoprecipitate the
      E complex. These observations indicate that U2 snRNP is associated with the E
      complex. However, we find that U2 snRNP is not as tightly bound in the E complex
      as it is in the A complex. The possible significance of the weak association of
      U2 snRNP with the E complex is discussed.

PMID- 9016567
TI  - Mixed backbone antisense oligonucleotides: design, biochemical and biological
      properties of oligonucleotides containing 2'-5'-ribo- and 3'-5'
      deoxyribonucleotide segments.
AB  - We have designed and synthesized mixed backbone oligonucleotides (MBOs)
      containing 2'-5'-ribo- and 3'-5'-deoxyribonucleotide segments. Thermal melting
      studies of the phosphodiester MBOs (three 2'-5'linkages at each end) with the
      complementary 3'-5'-DNA and -RNA target strands suggest that 2'-5'-ribonucleoside
      incorporation into 3'-5'-oligodeoxyribonucleotides reduces binding to the target
      strands compared with an all 3'-5'-oligodeoxyribonucleotide of the same sequence
      and length. Increasing the number of 2'-5'linkages (from six to nine) further
      reduces binding to the DNA target strand more than the RNA target strand
      [Kandimalla,E.R. and Agrawal,S. (1996)Nucleic Acids Symp. Ser., 35, 125-126].
      Phosphorothioate (PS) analogs of MBOs destabilize the duplex with the DNA target
      strand more than the duplex with the RNA target strand. Circular dichroism
      studies indicate that the duplexes of MBOs with the DNA and RNA target strands
      have spectral characteristics of both A- and B-type conformations. Compared with
      the control oligonucleotide, MBOs exhibit moderately higher stability against
      snake venom phosphodiesterase, S1 nuclease and in fetal calf serum. Although 2'
      5'modification does not evoke RNase H activity, this modification does not effect
      the RNase H activation property of the 3'-5'-deoxyribonucleotide segment adjacent
      to the modification. In vitro studies with MBOs suggest that they have lesser
      effects on cell proliferation, clotting prolongation and hemolytic complement
      lysis than do control PS oligodeoxyribonucleotides. PS analogs of MBOs show HIV-1
      inhibition comparable with that of a control PS oligodeoxyribonucleotide with all
      3'-5'linkages. The current results suggest that a limited number of 2'-5'linkages
      could be used in conjunction with PS oligonucleotides to further modulate the
      properties of antisense oligonucleotides as therapeutic agents.

PMID- 9016566
TI  - A common RNA structural motif involved in the internal initiation of translation
      of cellular mRNAs.
AB  - The 5'-non-translated regions (5'NTR) of human immunoglobulin heavy chain binding
      protein (BiP), Antennapedia (Antp) ofDrosophilaand human fibroblast growth factor
      2 (FGF-2) mRNAs are reported to mediate translation initiation by an internal
      ribosome binding mechanism. In this study, we investigate predicted features of
      the higher order structures folded in these 5'NTR sequences. Statistical analyses
      of RNA folding detected a 92 nt unusual folding region (UFR) from 129 to 220,
      close to the initiator AUG in the BiP mRNA. Details of the structural analyses
      show that the UFR forms a Y-type stem-loop structure with an additional stem-loop
      in the 3'-end resembling the common structure core found in the internal ribosome
      entry site (IRES) elements of picornavirus. The Y-type structural motif is also
      conserved among a number of divergent BiP mRNAs. We also find two RNA elements in
      the 5'-leader sequence of human FGF-2. The first RNA element (96 nt) is 2 nt
      upstream of the first CUG start codon located in the reported IRES element of
      human FGF-2. The second (107 nt) is immediately upstream of the authentic
      initiator AUG of the main open reading frame. Intriguingly, the folded RNA
      structural motif in the two RNA elements is conserved in other members of FGF
      family and shares the same structural features as that found in the 5'NTR of
      divergent BiP mRNAs. We suggest that the common RNA structural motif conserved in
      the diverse BiP and FGF-2 mRNAs has a general function in the internal ribosome
      binding mechanism of cellular mRNAs.

PMID- 9016568
TI  - HTLV-I Tax self-association in optimal trans-activation function.
AB  - HTLV-I Tax protein is a potent transcriptional activator of viral and cellular
      genes. Tax does not bind DNA directly but interacts through protein-protein
      contact with host cell factors that recognize the viral long terminal repeat
      (LTR). Domains within Tax needed for protein-protein interaction have not been
      fully characterized. In studying transcriptional function in yeast cells, we
      unexpectedly found that Tax functions optimally not as a monomer, but as a
      homodimer. Here we have used the one hybrid and two hybrid genetic approaches in
      yeast to investigate the region(s) within Tax necessary for self-association.
      Dimer formation was also confirmed biochemically by using electrophoretic
      mobility shift (EMSA) and supershift assays. Twenty two Tax point mutants were
      utilized to map relevant residues. Genetic results from this series of mutants
      revealed that a necessary region for dimerization is contained within a
      previously characterized zinc finger domain. Two loss-of-function Tax mutants,
      each poorly active when assayed individually, were found to have complementing
      activity when co-expressed together. This genetic complementation suggests a
      mechanism fortrans-activation resulting from simultaneous but non-identical
      contact with a responsive target by each of two Tax monomers in a dimer.

PMID- 9016569
TI  - Binding site of the M-domain of human protein SRP54 determined by systematic site
      directed mutagenesis of signal recognition particle RNA.
AB  - The interaction of protein SRP54M from the human signal recognition particle with
      SRP RNA was studied by systematic site-directed mutagenesis of the RNA molecule.
      Protein binding sites were identified by the analysis of mutations that removed
      individual SRP RNA helices or disrupted helical sections in the large SRP domain.
      The strongest effects on the binding activity of a purified polypeptide that
      corresponds to the methionine-rich domain of SRP54 (SRP54M) were caused by
      changes in helix 8 of the SRP RNA. Binding of protein SRP19 was diminished
      significantly by mutations in helix 6 and was stringently required for SRP54M to
      associate. Unexpectedly, mutant RNA molecules that resembled bacterial SRP RNAs
      were incapable of interaction with SRP54M, showing that protein SRP19 has an
      essential and direct role in the formation of the ternary complex with SRP54 and
      SRP RNA. Our findings provide an example for how, in eukaryotes, an RNA function
      has become protein dependent.

PMID- 9016571
TI  - RNA editing status of nad7 intron domains in wheat mitochondria.
AB  - The most highly conserved structures of group II introns are the helical domains
      V and VI near the 3'splice site. Within this region of each of the four introns
      in the wheat mitochondrial nad7 gene encoding NADH dehydrogenase subunit 7, there
      are A-C mispairs. To determine whether C-to-U type RNA editing restores
      conventional A-U pairing, we sequenced RT-PCR products from partially-spliced
      nad7 template RNA and gel-fractionated, excised intron RNA. We examined
      transcripts from germinating wheat embryos and seedlings because these two stages
      of development show pronounced differences in steady state levels of nad7
      intronic RNAs. We observed editing at only two of the six predicted sites, and
      they were located at homologous positions within domain V of the third and fourth
      introns. A third site was found to be edited within the unmodelled domain VI loop
      of the fourth intron. Similar patterns of RNA editing were seen in wheat embryos
      and seedlings. These observations, and the presence of other non-conventional
      base pairs particularly within domain V of plant mitochondrial introns, indicate
      weaker helical core structure than in ribozymic group II introns. Moreover, the
      incompleteness or absence of editing in wheat nad7 excised intron RNA suggests
      that, although editing may contribute to splicing efficiency, it is not essential
      for splicing.

PMID- 9016570
TI  - Cap-independent translation initiation in Xenopus oocytes.
AB  - Eukaryotic cellular mRNAs contain a cap at their 5'-ends, but some viral and
      cellular mRNAs bypass the cap-dependent mechanism of translation initiation in
      favor of internal entry of ribosomes at specific RNA sequences. Cap-dependent
      initiation requires intact initiation factor eIF4G (formerly eIF-4gamma, eIF
      4Fgamma or p220), whereas internal initiation can proceed with eIF4G cleaved by
      picornaviral 2A or L proteases. Injection of recombinant coxsackievirus B4
      protease 2A into Xenopus oocytes led to complete cleavage of endogenous eIF4G,
      but protein synthesis decreased by only 35%. Co-injection of edeine reduced
      synthesis by >90%, indicating that eIF4G-independent synthesis involved ongoing
      initiation. The spectrum of endogenous proteins synthesized was very similar in
      the presence or absence of intact eIF4G. Translation of exogenous rabbit globin
      mRNA, by contrast, was drastically inhibited by eIF4G cleavage. The N-terminal
      cleavage product of eIF4G (cpN), which binds eIF4E, was completely degraded
      within 6-12 h, while the C-terminal cleavage product (cpC), which binds to eIF3
      and eIF4A, was more stable over the same period. Thus, translation initiation of
      most endogenous mRNAs inXenopusoocytes requires no eIF4G, or perhaps only cpC,
      suggesting a cap-independent mechanism.

PMID- 9016572
TI  - Characterization of the autoantigen La (SS-B) as a dsRNA unwinding enzyme.
AB  - During the analysis of the La (SS-B) autoantigen for catalytic activities an ATP
      dependent double-stranded RNA unwinding activity was detected. Both native and
      recombinant La proteins from different species displayed this activity, which
      could be inhibited by monospecific anti-La antibodies. La protein was able to
      melt dsRNA substrates with either two 3'-overhangs or a single 3'- and a 5'
      overhang. Double-stranded RNAs with two 5'-overhangs were not unwound, indicating
      that at least one 3'-overhang is required for unwinding. Sequence elements of the
      La protein that might be involved in dsRNA unwinding, such as an evolutionarily
      conserved putative ATP-binding motif and an element that is homologous to the
      double-stranded RNA binding protein kinase PKR, are discussed.

PMID- 9016573
TI  - Sequence requirements of the bidirectional yeast TRP4 mRNA 3'-end formation
      signal.
AB  - The yeast TRP4 3'-end formation signal functions in both orientations in an in
      vivo test system. We show here that the TRP4 3'-end formation element consists of
      two functionally different sequence regions. One region of approximately 70
      nucleotides is located in the untranslated region between the translational stop
      codon and the major poly(A) site. The major poly(A) site is not part of this
      region and can be deleted without a decrease in TRP4 3'-end formation. 5'and
      3'deletions and point mutations within this region affected 3'-end formation
      similarly in both orientations. In the center of this region the motif TAGT is
      located on the antisense strand. Point mutations within this motif resulted in a
      drastic reduce of 3'-end formation activity in both orientations. A second region
      consists of the 3'-end of the TRP4 open reading frame and is required for 3'-end
      formation in forward orientation. A single point mutation in a TAGT motif of the
      TRP4 open reading frame abolished TRP4 mRNA 3'-end formation in forward
      orientation and had no effect on the reverse orientation.

PMID- 9016575
TI  - Expression of a reporter gene interrupted by the Candida albicans group I intron
      is inhibited by base analogs.
AB  - We previously reported the identification of an intron (CaLSU) in the 25S
      ribosomal RNA of some Candida albicans yeast strains. CaLSU was shown to self
      splice and has the potential to adopt a secondary structure typical of group I
      introns. The presence of CaLSU inC. albicans strains correlates with a high
      degree of susceptibility to base analog antifungal agents, 5-fluorocytosine (5
      FC) or 5-fluorouracil (5-FU). Cell death, resulting from addition of base analogs
      to growing cultures, precluded demonstration of a causal relationship between
      CaLSU presence and susceptibility to base analogs. In the present study, CaLSU
      was inserted in a non-essential lacZ reporter gene and expression was examined in
      Saccharomyces cerevisiae. Different mutations affecting in vitro self-splicing
      also had similar effects on reporter gene expression in vivo. This indicates that
      in vivo removal of CaLSU from the reporter gene occurs through the typical self
      splicing mechanism of group I introns. Base analogs inhibited expression of the
      reporter gene product in a concentration-dependent manner upon their addition to
      the cultures. This supports a model in which disruption of intron secondary
      structure, consecutive to the incorporation of nucleotide analogs, is a major
      factor determining the susceptibility of C.albicans cells to base analogs.

PMID- 9016574
TI  - Inhibition of muscle-specific gene expression by Id3: requirement of the C
      terminal region of the protein for stable expression and function.
AB  - We have examined the role of an Id-like protein, Id3 (also known as HLH462), in
      the regulation of muscle-specific gene expression. Id proteins are believed to
      block expression of muscle-specific genes by preventing the dimerization between
      ubiquitous bHLH proteins (E proteins) and myogenic bHLH proteins such as MyoD.
      Consistent with its putative role as an inhibitor of differentiation, Id3 mRNA
      was detected in proliferating skeletal muscle cells, was further induced by basic
      fibroblast growth factor (bFGF) and was down-regulated in differentiated muscle
      cultures. Overexpression of Id3 efficiently inhibited the MyoD-mediated
      activation of the muscle-specific creatine kinase (MCK) reporter gene. Deletion
      analysis indicated that the C-terminal 15 amino acids of Id3 are critical for the
      full inhibitory activity while deleting up to 42 residues from the C-terminus of
      the related protein, Id2, did not affect its ability to inhibit the MCK reporter
      gene. Chimeric protein containing the N-terminal region of Id3 and the C-terminus
      of Id2 was also non-functional in transfected cells. In contrast, wild-type Id3,
      the C-terminal mutants, and the Id3/Id2 chimera could all interact with the E
      protein E47in vitro. Additional studies indicated that truncation of the Id3 C
      terminus might have adversely affected the expression level of the mutant
      proteins but the Id3/Id2 chimera was stably expressed. Taken together, our
      results revealed a more complex requirement for the expression and proper
      function of the Id family proteins than was hitherto expected.

PMID- 9016577
TI  - Alanine-stretch scanning mutagenesis: a simple and efficient method to probe
      protein structure and function.
AB  - We have developed a foolproof method to substitute a stretch of residues by
      alanines. After the introduction of aPstI site by IPCR, thus creating two alanine
      codons, additional codons are introduced at this site through the use of an
      'alanine-stretch cartridge'. These cartridges comprise an antibiotic resistance
      gene flanked on both sides by alanine codons. Excision of the resistance gene
      byPvuII then yields the correct insertion of codons. The method is both highly
      reliable and flexible and should be of general use.

PMID- 9016576
TI  - Identification of additional rRNA fragments encoded by the Plasmodium falciparum
      6 kb element.
AB  - Sequences similar to mitochondrial large and small subunit rRNAs are found as
      small scattered fragments on a tandemly reiterated 6 kb element in the human
      malaria parasite Plasmodium falciparum. The rDNA sequences previously identified
      include strongly conserved portions of rRNA, suggesting that fragmented rRNAs
      derived from them are able to associate into functional ribosomes. However,
      sequences corresponding to other expected rRNA regions were not found. We here
      report that 10 of the 13 previously described rDNA regions have abundant small
      transcripts. An additional 10 transcripts were found from regions not previously
      known to contain genes. Five of the latter have been identified as rRNA
      fragments, including those corresponding to the 5'end and 790 loop sequences of
      small subunit rRNA and the sarcin/ ricin loop of large subunit rRNA.
      Demonstration that most of the previously described rDNA regions have abundant
      transcripts and the identification of new transcripts with other portions of
      conventional rRNAs provide support for the hypothesis that these small
      transcripts comprise functional rRNAs.

PMID- 9016578
TI  - Transcription from plasmid expression vectors is increased up to 14-fold when
      plasmids are transfected as concatemers.
AB  - A protocol for increasing transcription from plasmid expression vectors is
      presented. A vector containing chloramphenicol acetyltransferase (CAT) gene was
      digested leaving the transcription cassette intact. Heat inactivation of
      restriction enzymes followed by ligation of the digestion products yielded
      concatemers which migrated as a single band in agarose gel electrophoresis. Mouse
      fibroblasts transfected with the concatemers gave a CAT activity that was 14-fold
      greater than that of cells transfected with a similar mass (equimolar gene
      number) of the native plasmid. The effect was independent of promoter type,
      restriction enzyme, number of restriction sites and with a noted exception, cell
      line.

PMID- 9016579
TI  - Recombination-mediated PCR-directed plasmid construction in vivo in yeast.
AB  - We have extended the technique of PCR-directed recombination in Saccharomyces
      cerevisiae to develop a simple method for plasmid or gene construction in the
      absence of suitable restriction sites. The DNA to be cloned is PCR-amplified with
      30-40 bp of homology to a linearized yeast plasmid. Co-transformation into yeast
      results in homologous recombination at a position directed by the PCR
      oligonucleotides.

PMID- 9016580
TI  - Solid phase technology improves coupled gel shift/footprinting analysis.
AB  - For the analysis of protein-DNA interactions by coupled gel-shift/footprinting,
      DNA fragments need to be extracted from polyacrylamide gels and subsequently
      separated on high resolution gels. Due to impurities in the extracted DNA, single
      nucleotide resolution is frequently not achieved. We now describe an improved
      experimental strategy that employs transient coupling of DNA fragments to a solid
      support in order to extract DNA of high purity quantitatively, rapidly and
      reliably. As an example, we describe the application of our protocol to the 'in
      gel footprinting' by copper phenanthroline. The method should also find
      application to the chemical interference assays.

PMID- 9016581
TI  - Conceptual translation of timeless reveals alternative initiating methionines in
      Drosophila.
AB  - We have sequenced genomic fragments which encode the N-terminus of the TIMELESS
      (TIM) clock protein in Drosophila simulans and D. yakuba. We observe that in
      these two species, the initiating methionine appears to lie downstream of the one
      proposed to encode the translational start inD.melanogaster, thereby truncating
      the N-terminus by 23 amino acids. We then sequenced the corresponding 5'fragment
      in a number of D. melanogaster individuals from different strains. We observed a
      polymorphism which strongly suggests that the originally proposed start site
      cannot be utilised in some individuals, and that these flies will initiate
      translation of TIM at the downstream ATG. Given the current interest in TIM
      regulation in D. melanogaster, it is important to correctly define the N-terminus
      in this species.

PMID- 9016582
TI  - The AT-rich flanks of the oocyte-type 5S RNA gene of Xenopus laevis act as a
      strong local signal for histone H1-mediated chromatin reorganization in vitro.
AB  - In vivo, histone H1 plays an active role in establishing the transcriptionally
      repressed chromatin state of the oocyte-type 5S RNA genes in the early stages of
      Xenopus development. By using fully defined in vitro system of chromatin assembly
      on plasmids with cloned oocyte- or somatic-type 5S gene repeats we found that the
      oocyte repeat which comprises a 120 bp oocyte-type 5S RNA gene placed within the
      few hundred bp long native AT-rich flanks, but not the somatic repeat (a similar
      120 bp somatic-type 5S RNA gene placed within native GC-rich flanks) enables
      histone H1 to realign the nucleosomal core particles densely packed on plasmid
      DNA. The realignment results in creation of the repeat unit of approximately 240
      bp and is achieved through complete removal of several core histone complexes
      from plasmid template with the oocyte-type repeat. This effect of H1 is
      independent on the plasmid sequences and seems to be solely due to the presence
      in the oocyte-repeat of the AT-rich flanks. The effects of H1 are completely
      suppressed by distamycin A, a drug that specifically recognizes and binds
      oligo(dA).oligo(dT) runs in DNA. The binding of H1 results in increased
      protection of DNA sites within the AT-rich oocyte-type 5S repeat. In an in vitro
      transcription assay performed with reconstituted chromatin templates containing
      plasmids with the oocyte- or somatic-type repeats only the transcription of the
      oocyte-type 5S RNA gene was repressed in the presence of physiological
      concentration of histone H1. These results support the view that the AT-rich
      flanks of the oocyte-type 5S RNA gene are involved in histone H1-mediated
      chromatin reorganization that results in the transcriptional repression observed
      in vivo.

PMID- 9016583
TI  - Molecular weight abnormalities of the CTCF transcription factor: CTCF migrates
      aberrantly in SDS-PAGE and the size of the expressed protein is affected by the
      UTRs and sequences within the coding region of the CTCF gene.
AB  - CTCF belongs to the Zn finger transcription factors family and binds to the
      promoter region of c-myc. CTCF is highly conserved between species, ubiquitous
      and localised in nuclei. The endogenous CTCF migrates as a 130 kDa (CTCF-130)
      protein on SDS-PAGE, however, the open reading frame (ORF) of the CTCF cDNA
      encodes only a 82 kDa protein (CTCF-82). In the present study we investigate this
      phenomenon and show with mass-spectra analysis that this occurs due to aberrant
      mobility of the CTCF protein. Another paradox is that our original cDNA, composed
      of the ORF and 3'-untranslated region (3'-UTR), produces a protein with the
      apparent molecular weight of 70 kDa (CTCF-70). This paradox has been found to be
      an effect of the UTRs and sequences within the coding region of the CTCF gene
      resulting in C-terminal truncation of CTCF-130. The potential attenuator has been
      identified and point-mutated. This restored the electrophoretic mobility of the
      CTCF protein to 130 kDa. CTCF-70, the aberrantly migrating CTCF N-terminus per
      se, is also detected in some cell types and therefore may have some biological
      implications. In particular, CTCF-70 interferes with CTCF-130 normal function,
      enhancing transactivation induced by CTCF-130 in COS6 cells. The mechanism of
      CTCF-70 action and other possible functions of CTCF-70 are discussed.

PMID- 9016584
TI  - Kinetics of excision of purine lesions from DNA by Escherichia coli Fpg protein.
AB  - The kinetics of excision of damaged purine bases from oxidatively damaged DNA by
      Escherichia coli Fpg protein were investigated. DNA substrates, prepared by
      treatment with H2O2/Fe(III)-EDTA or by gamma-irradiation under N2O or air, were
      incubated with Fpg protein, followed by precipitation of DNA. Precipitated DNA
      and supernatant fractions were analyzed by gas chromatography/isotope-dilution
      mass spectrometry. Kinetic studies revealed efficient excision of 8
      hydroxyguanine (8-OH-Gua), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua)
      and 4, 6-diamino-5-formamidopyrimidine (FapyAde). Thirteen other modified bases
      in the oxidized DNA substrates, including 5-hydroxycytosine and 5-hydroxyuracil,
      were not excised. Excision was measured as a function of enzyme concentration,
      substrate concentration, time and temperature. The rate of release of modified
      purine bases from the three damaged DNA substrates varied significantly even
      though each DNA substrate contained similar levels of oxidative damage.
      Specificity constants (kcat/KM) for the excision reaction indicated similar
      preferences of Fpg protein for excision of 8-OH-Gua, FapyGua and FapyAde from
      each DNA substrate. These findings suggest that, in addition to 8-OH-Gua, FapyGua
      and FapyAde may be primary substrates for this enzyme in cells.

PMID- 9016585
TI  - Differential human nucleotide excision repair of paired and mispaired cisplatin
      DNA adducts.
AB  - In order to understand the action of the chemotherapeutic drug cisplatin, it is
      necessary to determine why some types of cisplatin-DNA intrastrand crosslinks are
      repaired better than others. Using cell extracts and circular duplex DNA, we
      compared nucleotide excision repair of uniquely placed 1,2-GG, 1,2-AG, and 1,3
      GTG cisplatin-crosslinks, and a 2-acetylaminofluorene lesion. The 1,3 crosslink
      and the acetylaminofluorene lesion were repaired by normal cell extracts
      approximately 15-20 fold better than the 1,2 crosslinks. No evidence was found
      for selective shielding of 1,2 cisplatin crosslinks from repair by cellular
      proteins. Fractionation of cell extracts to remove putative shielding proteins
      did not improve repair of the 1,2-GG crosslink, and cell extracts did not
      selectively inhibit access of UvrABC incision nuclease to 1,2-GG crosslinks. The
      poorer repair of 1,2 crosslinks in comparison to the 1,3 crosslink is more likely
      a consequence of different structural alterations of the DNA helix. In support of
      this, a 1,2-GG-cisplatin crosslink was much better repaired when it was opposite
      one or two non-complementary thymines. Extracts from cells defective in the
      hMutSalpha mismatch binding activity also showed preferential repair of the 1,3
      crosslink over the 1,2 crosslink, and increased repair of the 1,2 adduct when
      opposite thymines, showing that hMutSalphais not involved in the differential NER
      of these substrates in vitro. Mismatched cisplatin adducts could arise by
      translesion DNA synthesis, and improved repair of such adducts could promote
      cisplatin-induced mutagenesis in some cases.

PMID- 9016586
TI  - Selective recognition of a cisplatin-DNA adduct by human mismatch repair
      proteins.
AB  - The antitumor agent cis-diamminedichloroplatinum(II) (cisplatin) introduces
      cytotoxic DNA damage predominantly in the form of intrastrand crosslinks between
      adjacent purines. Binding assays using a series of duplex oligonucleotides
      containing a single 1,2 diguanyl intrastrand crosslink indicate that human cell
      extracts contain factors that preferentially recognise this type of damage when
      the complementary strand contains T opposite the 3', and C opposite the 5'guanine
      in the crosslink. Under the conditions of the band-shift assay used, little
      binding is observed if the positions of the T and C are reversed in the
      complementary strand. Similarly, duplexes containing CC or TT opposite the
      crosslink are recognised relatively poorly. The binding activity is absent from
      extracts of the colorectal carcinoma cell lines LoVo and DLD-1 in which the
      hMutSalpha mismatch recognition complex is inactivated by mutation. Extensively
      purified human hMutSalpha exhibits the same substrate preference and binds to the
      mismatched platinated DNA at least as well as to an identical unplatinated duplex
      containing a single G.T mismatch. It is likely, therefore, that human mismatch
      repair may be triggered by 1,2 diguanyl intrastrand crosslinks that have
      undergone replicative bypass.

PMID- 9016587
TI  - Optimal Tat-mediated activation of the HIV-1 LTR promoter requires a full-length
      TAR RNA hairpin.
AB  - HIV-1 transcription from the LTR promoter is activated by the viral Tat protein
      through interaction with the nascent TAR RNA hairpin structure. The mechanism of
      Tat-mediated transcriptional activation has been extensively investigated with
      LTR-CAT reporter genes in transient transfections and, more recently, in
      infection experiments with mutant HIV-1 variants. Several discrepancies between
      these two assay systems have been reported. For instance, whereas opening of the
      lower part of the TAR RNA stem does not affect the promoter activity of an LTR
      CAT plasmid in transient assays, the corresponding virus mutant is fully
      replication-impaired. With the aim to resolve this controversy, we have examined
      the activity of a set of TAR RNA mutants in transient transfection experiments
      with a variety of cell types. We now demonstrate that truncated TAR motifs
      exhibit a severe, but cell-type dependent transcription defect. Whereas full LTR
      activity is measured in COS cells that have been used regularly in previous
      transfection assays, a severe defect is apparent in a variety of human cell
      lines, including T cell lines that are typically used in HIV-1 replication
      studies. These results suggest the presence of a human protein that participates
      in Tat-mediated transcriptional activation through binding to the lower part of
      the TAR stem. Several candidate co-factors have been reported in literature. This
      study resolves the discrepancy between transfection and infection studies on the
      requirements of the lower TAR stem structure. The evidence also implies that LTR
      transcription studies should be performed preferentially in human cell types.

PMID- 9016588
TI  - The HsdR subunit of R.EcoR124II: cloning and over-expression of the gene and
      unexpected properties of the subunit.
AB  - Type I restriction endonucleases are composed of three subunits, HsdR, HsdM and
      HsdS. The HsdR subunit is absolutely required for restriction activity; while an
      independent methylase is composed of HsdM and HsdS subunits. DNA cleavage is
      associated with a powerful ATPase activity during which DNA is translocated by
      the enzyme prior to cleavage. The presence of a Walker type I ATP-binding site
      within the HsdR subunit suggested that the subunit may be capable of independent
      enzymatic activity. Therefore, we have, for the first time, cloned and over
      expressed the hsdRgene of the type IC restriction endonuclease EcoR124II. The
      purified HsdR subunit was found to be a soluble monomeric protein capable of DNA-
      and Mg2+-dependent ATP hydrolysis. The subunit was found to have a weak nuclease
      activity both in vivo and in vitro, and to bind plasmid DNA; although was not
      capable of binding a DNA oligoduplex. We were also able to reconstitute the fully
      active endonuclease from purified M. EcoR124I and HsdR. This is the first clear
      demonstration that the HsdR subunit of a type I restriction endonuclease is
      capable of independent enzyme activity, and suggests a mechanism for the
      evolution of the endonuclease from the independent methylase.

PMID- 9016589
TI  - Structural analysis of mouse rDNA: coincidence between nuclease hypersensitive
      sites, DNA curvature and regulatory elements in the intergenic spacer.
AB  - We have analyzed the chromatin structure of mouse ribosomal RNA genes (rDNA) by
      partial digestion of genomic DNA with micrococcal nuclease (MNase), DNase I and
      identified hypersensitive sites by indirect end-labeling. This analysis has
      revealed defined regions of nuclease hypersensitivity in the intergenic spacer
      which in turn coincide with regulatory elements. Hypersensitive sites map to the
      transcription initiation site, the enhancer repeats, the spacer promoter and two
      sequence elements which coincide with amplification-promoting sequences. Analysis
      of the DNA curvature by computer modeling uncovered a striking correlation
      between sequence-directed structural features of regulatory regions and the
      position of nuclease hypersensitive sites. Moreover, we demonstrate that
      nucleosomes are specifically positioned upstream and downstream of the
      transcription start site. In vitro studies using chromatin assembled in the
      presence of Drosophila embryo extracts show that binding of the transcription
      termination factor TTF-I to the upstream terminator mediates this specific
      nucleosome positioning at the rDNA promoter in an ATP- dependent fashion.

PMID- 9016590
TI  - Polynucleotide:adenosine glycosidase activity of ribosome-inactivating proteins:
      effect on DNA, RNA and poly(A).
AB  - Ribosome-inactivating proteins (RIP) are a family of plant enzymes for which a
      unique activity was determined: rRNAN-glycosidase at a specific universally
      conserved position, A4324in the case of rat ribosomes. Recently we have shown
      that the RIP from Saponaria officinalis have a much wider substrate specificity:
      they are actually polynucleotide:adenosine glycosidases. Here we extend studies
      on substrate specificity to most known RIP: 52 purified proteins, both type 1
      (single-chain) and type 2 (two chain, an enzymatic chain and a lectin chain) were
      examined for adenine release on various substrates including RNAs from different
      sources, DNA, and poly(A). All RIP depurinated extensively DNA and some released
      adenine from all adenine-containing polynucleotides tested. From experimental
      evidence the entire class of plant proteins, up to now called ribosome
      inactivating proteins, may be classified as polynucleotide:adenosine
      glycosidases. The newly identified substrates may be implicated in the biological
      role(s) of RIP.

PMID- 9016591
TI  - DIR: a novel DNA rearrangement associated with inverted repeats.
AB  - A novel DNA rearrangement has been characterised that is both a direct and
      inverted repeat. This rearrangement involves the 2-fold duplication of a plasmid
      sequence adjacent to the site of insertion of a long palindrome. The sequence of
      this rearrangement suggests that it has arisen by strand slippage from the
      leading to the lagging strand of the replication fork as a consequence of the
      presence of the long palindrome.

PMID- 9016592
TI  - Identification of a predominant replication origin in fission yeast.
AB  - We have identified five autonomously replicating sequences (ARSs) in a 100 kbp
      region of the Schizosaccharomyces pombe chromosome II. Analyses of replicative
      intermediates of the chromosome DNA by neutral/neutral two-dimensional gel
      electrophoresis demonstrated that at least three of these ARS loci operate as
      chromosomal replication origins. One of the loci,ori2004, was utilized in almost
      every cell cycle, while the others were used less frequently. The frequency of
      initiation from the respective chromosomal replication origin was found to be
      roughly proportional to the efficiency of autonomous replication of the
      corresponding ARS plasmid. Replication from ori2004 was initiated within a
      distinct region almost the same as that for replication of the ARS plasmid. These
      results showed that the ori2004 region of approximately 3 kbp contains all the
      cis elements essential for initiation of chromosome replication.

PMID- 9016594
TI  - Two step synthesis of (-) strong-stop DNA by avian and murine reverse
      transcriptases in vitro.
AB  - Retroviral reverses transcriptases (RTs) are RNA- and DNA-dependent DNA
      polymerases that use a tRNA bound at the so-called primer binding site (PBS)
      located near the 5'end of the genomic RNA as primer. Thus, RTs must be able to
      accommodate both RNA and DNA in the primer strand. To test whether the natural
      primer confers some advantages to the priming process, we compared initiation of
      reverse transcription of avian and murine retroviral RNAs, using either their
      natural tRNA primer, tRNATrp and tRNAPro, respectively, or synthetic 18mer
      oligodeoxyribonucleotides (ODNs) and oligoribonucleotides (ORNs) complementary to
      their PBS. In both retroviral systems, the initial extension of ODNs was fast and
      processive. The initial extension of ORNs, tRNATrp and tRNAPro was much slower
      and distributive, giving rise to the transient accumulation of short pausing
      products. Synthesis of (-) strong-stop DNA was delayed when using ORNs and tRNAs,
      compared to ODNs. Even though ORNs and tRNAs were initially extended at the same
      rate, the short pausing products were more rapidly extended when using the tRNA
      primers. As a consequence, synthesis of (-) strong-stop DNA was much more
      efficient with tRNA primers, compared to ORNs. Taken together, these results
      suggest that the tRNA-primed synthesis of (-) strong-stop DNA is a two-step
      process, as already observed for HIV-1. The initiation mode corresponds to the
      initial non-processive nucleotide addition and extension of the short pausing
      products. It is more efficient with the natural primers than with ORNs.
      Initiation is followed by a more processive and unspecific elongation mode.
      Elongation is observed when the primer strand is DNA, i.e. when using the ODNs as
      primers or when the ORN and tRNA primers have been extended by a sufficient
      number (depending on the retroviral system) of deoxyribonucleotides.

PMID- 9016593
TI  - Characterization of DbpA, an Escherichia coli DEAD box protein with ATP
      independent RNA unwinding activity.
AB  - DbpA is a putative Escherichia coli ATP dependent RNA helicase belonging to the
      family of DEAD box proteins. It hydrolyzes ATP in the presence of 23S ribosomal
      RNA and 93 bases in the peptidyl transferase center of 23S rRNA are sufficient to
      trigger 100% of the ATPase activity of DbpA. In the present study we
      characterized the ATPase and RNA unwinding activities of DbpA in more detail. We
      report that-in contrast to eIF-4A, the prototype of the DEAD box protein family
      the ATPase and the helicase activities of DbpA are not coupled. Moreover, the RNA
      unwinding activity of DbpA is not specific for 23S rRNA, since DbpA is also able
      to unwind 16S rRNA hybrids. Furthermore, we determined that the ATPase activity
      of DbpA is triggered to a significant extent not only by the 93 bases of the 23S
      rRNA previously reported but also by other regions of the 23S rRNA molecule.
      Since all these regions of 23S rRNA are either part of the 'functional core' of
      the 50S ribosomal subunit or involved in the 50S assembly, DbpA may play an
      important role in the ribosomal assembly process.

PMID- 9016595
TI  - Solid phase synthesis and restriction endonuclease cleavage of
      oligodeoxynucleotides containing 5-(hydroxymethyl)-cytosine.
AB  - Emerging data suggest an important role for cytosine methylation in
      tumorigenesis. Simultaneously, recent studies indicate a significant contribution
      of endogenous oxidative DNA damage to the development of human disease. Oxidation
      of the 5-methyl group of 5-methylcytosine (5mC) residues in DNA results in the
      formation of 5-(hydroxymethyl)cytosine (hmC). The biological consequences ofhmC
      residues in vertebrate DNA are as yet unknown; however, conversion of the
      hydrophobic methyl group to the hydrophilic hydroxymethyl group may substantially
      alter the interaction of sequence-specific binding proteins with DNA. Central to
      both biophysical and biochemical studies on the potential consequences of
      specific DNA damage products such as hmC are efficient methods for the synthesis
      of oligodeoxynucleotides containing such modified bases at selected positions. In
      this paper, we describe a method for the placement of hmC residues in
      oligodeoxynucleotides using established phosphoramidite chemistry. In addition,
      we have examined the influence of specific hmC residues on enzymatic cleavage of
      oligodeoxynucleotides by the methylation-sensitive restriction endonucleases MspI
      and HpaII.

PMID- 9016596
TI  - The synthesis and stability of oligodeoxyribonucleotides containing the
      deoxyadenosine mimic 1-(2'-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide.
AB  - Oligodeoxyribonucleotides containing the nucleoside analog 1-(2'-deoxy-beta-D
      ribofuranosyl) imidazole-4-carboxamide (1) were synthesized by solid phase
      phosphoramidite technology. Nucleoside 1, which contains a reactive exocyclic
      amide moiety, was incorporated into synthetic oligodeoxyribonucleotides with the
      use of a benzoyl protecting group. The corresponding oligodeoxyribonucleotides
      with dI or dA in the same position in the sequence were synthesized for UV
      comparison of helix-coil transitions. The thermal melting studies indicate that
      1, which could conceptually adopt either a dA- or a dI-like hydrogen bond
      configuration, pairs with significantly higher affinity to T than to dC.
      Nucleoside 1 further resembles dA in the relative order of its base pairing
      preferences (T >dG >dA >dC), but may be less discriminating than dA in its bias
      for base pairing with T over dG.

PMID- 9016597
TI  - Evaluation of pyrimidine PNA binding to ssDNA targets from nonequilibrium melting
      experiments.
AB  - Slow kinetics of homopyrimidine PNA binding to single stranded DNA and RNA
      targets is manifested in significant hysteresis in thermal UV absorption
      experiments. We have compared temperatures of dissociation (Tdis) and
      reassociation (Tass) for triplexes formed by DNA and single or bis PNAs with K50
      derived from gel mobility experiments. Results indicated there was no correlation
      between Tdis and K50 while reasonable correlation between Tass and K50 was found.
      This correlation enabled use of easy thermal UV absorption experiments for
      evaluation of PNA binding to DNA/RNA targets.

PMID- 9016598
TI  - Sequence-independent inhibition of RNA transcription by DNA dumbbells and other
      decoys.
AB  - DNA dumbbells are stable, short segments of double-stranded DNA with closed
      nucleotide loops on each end, conferring resistance to exonucleases. Dumbbells
      may be designed to interact with transcription factors in a sequence-specific
      manner. The internal based paired sequence of DNA dumbbells in this study
      contains the X-box, a positive regulatory motif found in all MHC class II DRA
      promoters. In electrophoretic mobility shift assays (EMSAs), dumbbells and other
      oligonucleotides ('decoys') with the core X-box sequence were found to compete
      with the native strand for binding to X-box binding proteins (including RFX1).
      However, only the X-box dumbbell was capable of forming detectable complexes with
      such proteins using EMSA. In a model cell system, dumbbells were tested for their
      ability to block RFX1VP16 activation of a plasmid containing multiple repeats of
      the X-box linked to the CAT gene. While it appeared that dumbbells could block
      this activation, the effect was non-specific. This and further evidence suggests
      an inhibition of transcription, most likely via an interaction with the general
      transcriptional machinery.

PMID- 9016600
TI  - Reorganization of terminator DNA upon binding replication terminator protein:
      implications for the functional replication fork arrest complex.
AB  - Termination of DNA replication in Bacillus subtilis involves the polar arrest of
      replication forks by a specific complex formed between the replication terminator
      protein (RTP) and DNA terminator sites. While determination of the crystal
      structure of RTP has facilitated our understanding of how a single RTP dimer
      interacts with terminator DNA, additional information is required in order to
      understand the assembly of a functional fork arrest complex, which requires an
      interaction between two RTP dimers and the terminator site. In this study, we
      show that the conformation of the major B.subtilis DNA terminator,TerI, becomes
      considerably distorted upon binding RTP. Binding of the first dimer of RTP to the
      B site of TerI causes the DNA to become slightly unwound and bent by
      approximately 40 degrees. Binding of a second dimer of RTP to the A site causes
      the bend angle to increase to approximately 60 degrees . We have used this new
      data to construct two plausible models that might explain how the ternary
      terminator complex can block DNA replication in a polar manner. In the first
      model, polarity of action is a consequence of the two RTP-DNA half-sites having
      different conformations. These different conformations result from different RTP
      DNA contacts at each half-site (due to the intrinsic asymmetry of the terminator
      DNA), as well as interactions (direct or indirect) between the RTP dimers on the
      DNA. In the second model, polar fork arrest activity is a consequence of the
      different affinities of RTP for the A and B sites of the terminator DNA,
      modulated significantly by direct or indirect interactions between the RTP
      dimers.

PMID- 9016599
TI  - Unique features of the mitochondrial rolling circle-plasmid mp1 from the higher
      plant Chenopodium album (L.).
AB  - We analyzed the structure and replication of the mitochondrial (mt) circular DNA
      plasmid mp1 (1309 bp) from the higher plant Chenopodium album(L.). Two
      dimensional gel electrophoresis (2DE) revealed the existence of oligomers of up
      to a decamer in addition to the prevailing monomeric form. The migration behavior
      of cut replication intermediates during 2DE was consistent with a rolling circle
      (RC) type of replication. We detected entirely single-stranded (ss) plasmid
      copies hybridizing only with one of the two DNA strands. This result indicates
      the occurence of an asymmetric RC replication mechanism. mp1 has, with respect to
      its replication, some unique features compared with bacterial RC plasmids. We
      identified and localized a strand-specific nicking site (origin of RC
      replication) on the plasmid by primer extension studies. Nicks in the plasmid
      were found to occur at any one of six nucleotides (TAAG/GG) around position 735
      of the leading strand. This sequence shows no homology to origin motifs from
      known bacterial RC replicons. mp1 is the first described RC plasmid in a higher
      plant.

PMID- 9016602
TI  - In the presence of subunit A inhibitors DNA gyrase cleaves DNA fragments as short
      as 20 bp at specific sites.
AB  - A key step in the supercoiling reaction is the DNA gyrase-mediated cleavage and
      religation step of double-stranded DNA. Footprinting studies suggest that the DNA
      gyrase binding site is 100-150 bp long and that the DNA is wrapped around the
      enzyme with the cleavage site located near the center of the fragment. Subunit A
      inhibitors interrupt this cleavage and resealing cycle and result in cleavage
      occurring at preferred sites. We have been able to show that even a 30 bp DNA
      fragment containing a 20 bp preferred cleavage sequence from the pBR322 plasmid
      was a substrate for the DNA gyrase-mediated cleavage reaction in the presence of
      inhibitors. This DNA fragment was cleaved, although with reduced efficiency, at
      the same sites as a 122 bp DNA fragment. A 20 bp DNA fragment was cleaved with
      low efficiency at one of these sites and a 10 bp DNA fragment was no longer a
      substrate. We therefore propose that subunit A inhibitors interact with DNA at
      inhibitor-specific positions, thus determining cleavage sites by forming ternary
      complexes between DNA, inhibitors and DNA gyrase.

PMID- 9016601
TI  - Replication bypass and mutagenic effect of alpha-deoxyadenosine site-specifically
      incorporated into single-stranded vectors.
AB  - alpha-2'-Deoxyadenosine (alpha) is a major adenine lesion produced by gamma-ray
      irradiation of DNA under anoxic conditions. In this study, single-stranded
      recombinant M13 vectors containing alpha were constructed and transfected into
      Escherichia coli to assess lethal and mutagenic effects of this lesion. The data
      for alpha were further compared with those obtained with M13 vectors containing
      normal A or a model abasic site (F) at the same site. The transfection assay
      revealed that alpha constituted a moderate block to DNA replication. The in vivo
      replication capacity to pass through alpha was approximately 20% relative to
      normal A, but 20-fold higher than that of F constituting an almost absolute
      replication block. Similar data were obtained by in vitro replication of
      oligonucleotide templates containing alpha or F by E.coli DNA polymerase I. The
      mutagenic consequence of replicating M13 DNA containing alpha was analyzed by
      direct DNA sequencing of progeny phage. Mutagenesis was totally targeted at the
      site of alpha introduced into the vector. Mutation was exclusively a single
      nucleotide deletion and no base substitutions were detected. The deletion
      frequency associated alpha was dependent on the 3'-nearest neighbor base: with
      the 3'-nearest neighbor base T mutation (deletion) frequency was 26%, whereas 1%
      with the 3'-nearest neighbor base G. A possible mechanism of the single
      nucleotide deletion associated with alpha is discussed on the basis of the
      misinsertion-strand slippage model.

PMID- 9016603
TI  - The thermodynamic advantage of DNA oligonucleotide 'stacking hybridization'
      reactions: energetics of a DNA nick.
AB  - 'Stacking hybridization reactions' wherein two or more short DNA oligomers
      hybridize in a contiguous tandem orientation onto a longer complementary DNA
      single strand have been employed to enhance a variety of analytical
      oligonucleotide hybridization schemes. If the short oligomers anneal in perfect
      head-to-tail register the resulting duplex contains a nick at every boundary
      between hybridized oligomers. Alternatively, if the short oligomers do not
      hybridize precisely in register, i.e. single strand regions on the longer strand
      are left unbound, gaps are formed between regions where short oligomers bind. The
      resulting gapped DNA duplexes are considerably less stable than their nicked
      duplex analogs. Formation of base pair stacking interactions between neighboring
      oligomers at the nicks that do not occur in gapped duplexes has been proposed as
      the source of the observed added stability. However, quantitative evidence
      supporting this hypothesis for DNA has not been reported. Until now, a direct
      comparison of the thermodynamics of DNA nicks versus DNA gaps has not been
      performed. In this communication we report such a comparison. Analysis of optical
      melting experiments in a well defined molecular context enabled quantitative
      evaluations of the relative thermodynamic difference between nicked and gapped
      DNA duplexes. Results of the analysis reveal that a nick may be energetically
      favored over a gap by at least 1.4 kcal/mol and perhaps as much as 2.4 kcal/mol.
      The presence of a 5'phosphate at a nick or gap fails to significantly affect
      their stabilities.

PMID- 9016606
TI  - Potassium-resistant triple helix formation and improved intracellular gene
      targeting by oligodeoxyribonucleotides containing 7-deazaxanthine.
AB  - Triple helix formation by purine-rich oligonucleotides in the anti-parallel motif
      is inhibited by physiological concentrations of potassium. Substitution with 7
      deazaxanthine (c7X) has been suggested as a strategy to overcome this effect. We
      have tested this by examining triple helix formation both in vitro and in vivo by
      a series of triple helix-forming oligonucleotides (TFOs) containing guanine plus
      either adenine, thymine, or c7X. The TFOs were conjugated to psoralen at the
      5'end and were designed to bind to a portion of the supF mutation reporter gene.
      Using in vitro gel mobility shift assays, we found that triplex formation by the
      c7X-substituted TFOs was relatively resistant to the presence of 140 mM K+. The
      c7X-containing TFOs were also superior in gene targeting experiments in mammalian
      cells, yielding 4- to 5-fold higher mutation frequencies in a shuttle vector
      based mutagenesis assay designed to detect mutations induced by third strand
      directed psoralen adducts. When the phosphodiester backbone was replaced by a
      phosphorothioate one, the in vitro binding of the c7X-TFOs was not affected, but
      the efficiency of in vivo triple helix formation was reduced. These results
      indicate the utility of the c7X substitution for in vivo gene targeting
      experiments, and they show that the feasibility of the triplex anti-gene strategy
      can be significantly enhanced by advances in nucleotide chemistry.

PMID- 9016605
TI  - Mitochondrial tRNAs in the lower fungus Spizellomyces punctatus: tRNA editing and
      UAG 'stop' codons recognized as leucine.
AB  - The mitochondrial DNA of the chytridiomycete fungus Spizellomyces punctatusen
      codes only eight tRNAs, although a minimal set of 24-25 tRNAs is normally found
      in fungi. One of these tRNAs has a CAU anticodon and is structurally related to
      leucine tRNAs, which would permit the translation of the UAG 'stop' codons that
      occur in most of its protein genes. The predicted structures of all S. punctatus
      tRNAs have the common feature of containing one to three mis-pairings in the
      first three positions of their acceptor stems. Such mis-pairing is expected to
      impair proper folding and processing of tRNAs from their precursors. Five of
      these eight RNAs were shown to be edited at the RNA level, in the 5'portion of
      the molecules. These changes include both pyrimidine to purine and A to G
      substitutions that restore normal pairing in the acceptor stem. Editing was not
      found at other positions of the tRNAs, or in the mitochondrial mRNAs of S.
      punctatus. While tRNA editing has not been observed in other fungi, the editing
      pattern inS.punctatus is virtually identical to that described in the amoeboid
      protozoan Acanthamoeba castellanii. If this type of mitochondrial tRNA editing
      has originated from their common ancestor, one has to assume that it was
      independently lost in plants, animals and in most fungi. Alternatively, editing
      might have evolved independently, or the genes coding for the components of the
      editing machinery were laterally transferred.

PMID- 9016604
TI  - Divalent transition metal cations counteract potassium-induced quadruplex
      assembly of oligo(dG) sequences.
AB  - Nucleic acids containing tracts of contiguous guanines tend to self-associate
      into four-stranded (quadruplex) structures, based on reciprocal non-Watson-Crick
      (G*G*G*G) hydrogen bonds. The quadruplex structure is induced/stabilized by
      monovalent cations, particularly potassium. Using circular dichroism, we have
      determined that the induction/stabilization of quadruplex structure by K+is
      specifically counteracted by low concentrations of Mn2+(4-10 mM), Co2+(0.3-2 mM)
      or Ni2+(0.3-0.8 mM). G-Tract-containing single strands are also capable of
      sequence-specific non-Watson-Crick interaction with d(G. C)-tract-containing
      (target) sequences within double-stranded DNA. The assembly of these G*G.C-based
      triple helical structures is supported by magnesium, but is potently inhibited by
      potassium due to sequestration of the G-tract single strand into quadruplex
      structure. We have used DNase I protection assays to demonstrate that competition
      between quadruplex self-association and triplex assembly is altered in the
      presence of Mn2+, Co2+or Ni2+. By specifically counteracting the
      induction/stabilization of quadruplex structure by potassium, these divalent
      transition metal cations allow triplex formation in the presence of K+and shift
      the position of equilibrium so that a very high proportion of triplex target
      sites are bound. Thus, variation of the cation environment can differentially
      promote the assembly of multistranded nucleic acid structural alternatives.

PMID- 9016607
TI  - Conserved RY-repeats mediate transactivation of seed-specific promoters by the
      developmental regulator PvALF.
AB  - Transcription of genes DLEC2 and PHSbeta is specifically and coordinately
      regulated during maturation of Phaseolus embryos. Over-expression of the seed-
      specific factor PvALF in cotyledon cells results in transactivation of either
      promoter. PvALF is related to the VP1 protein of maize, which transactivates gene
      expression via G-boxes, Sph elements and AT-rich sequences. We used deletions and
      base substitutions in the DLEC2 and PHSbeta promoters to demonstrate that several
      conserved RY-repeats were necessary for PvALF induction of both genes. A
      comprehensive mutational and transactivation analysis was used to define
      functionally the sequence of the DLEC2 repeat RY3 asG/CCATGCxxG/C. We also found
      that an interaction between RY3 and the 3'-flanking tetranucleotide CCAC
      increased PvALF transactivation. A preferred spacing and phasing requirement for
      the RY3 and CCAC motifs suggested the possibility of interactions between
      cellular factors that recognize either element. The high conservation of Sph-RY
      motifs in seed-specific promoters from monocots and dicots indicates that organ
      and temporal specification by factors similar to VP1 and PvALF is common among
      seed plants.

PMID- 9016608
TI  - Metal ion interaction with cosubstrate in self-splicing of group I introns.
AB  - The catalytic mechanism for self-splicing of the group I intron in the pre-mRNA
      from the nrdB gene in bacteriophage T4 has been investigated using 2'-amino- 2'
      deoxyguanosine or guanosine as cosubstrates in the presence of Mg2+, Mn2+and
      Zn2+. The results show that a divalent metal ion interacts with the cosubstrate
      and thereby influences the efficiency of catalysis in the first step of splicing.
      This suggests the existence of a metal ion that catalyses the nucleophilic attack
      of the cosubstrate. Of particular significance is that the transesterification
      reactions of the first step of splicing with 2'-amino-2'-deoxyguanosine as
      cosubstrate are more efficient in mixtures containing either Mn2+or Zn2+together
      with Mg2+than with only magnesium ions present. The experiments in metal ion
      mixtures show that two (or more) metal ions are crucial for the self-splicing of
      group I introns and suggest the possibility that more than one of these have a
      direct catalytic role. A working model for a two-metal-ion mechanism in the
      transesterification steps is suggested.

PMID- 9016609
TI  - The effects of internal primer-template mismatches on RT-PCR: HIV-1 model
      studies.
AB  - We investigated the effects of internal primer-template mismatches on the
      efficiency of reverse transcription and PCR amplification. As models, RNA
      transcripts representative of different HIV-1 group M subtypes were evaluated
      with a previously described gag primer pair system. We observed that the presence
      of two to four mismatches in the primer-template duplexes did not have a
      significant effect on RT-PCR. However, the presence of five and six mismatches
      with the 28 and 30 base primers reduced PCR product yield by approximately 22-
      and 100-fold respectively, relative to the homologous template. The amount of
      reduction was reproducible from experiment to experiment and was independent of
      the initial copy number input. Under the conditions used, viral RNA measurements
      of the more divergent HIV-1 subtypes (A and E) would be underestimated, while
      isolates of subtypes B, C, D and F-H are expected to be efficiently amplified and
      accurately measured. The reduced amplification efficiency for targets similar to
      HIV subtypes A and E can be improved 4- to 10-fold by lowering the annealing
      temperature and implementing a reverse transcription step that gradually
      increases in temperature. The additional substitution of either 5-methylcytosine
      for cytosine throughout or the substitution of inosine at positions of variable
      bases resulted in a <4-fold difference in product yield between the homologous
      and most divergent templates.

PMID- 9016611
TI  - Altered structure of the DNA duplex recognized by yeast transcription factor
      Reb1p.
AB  - The Saccharomyces cerevisiae REB1 gene encodes a sequence-specific DNA binding
      protein that has been implicated in chromatin structure, transcription regulation
      and transcription termination. Previous work has shown that the DNA sequence
      recognized by Reb1p contains an adenosine residue that is unusually reactive
      toward chemical modification by dimethylsulfate and that methylation of this
      nucleoside increases the binding affinity of the Reb1p protein for its target.
      Prompted by these results, we determined the solution structure of the 13mer
      Reb1p DNA duplex recognition site d(GTCCGGGTAATGC).d(GCATTACCCGGAC) using 2D NMR,
      distance geometry and iterative 2D NOESY back-calculation structure refinement.
      The distance geometry-refined molecule demonstrated an unusual structure in the
      TAAT region of the sequence that was manifested in cross-strand base stacking, as
      indicated by unusually strong NOE interactions between H2 protons on three
      adjacent adenosine bases. This structure was compared to two published NMR
      studies of DNA duplexes containing the related sequence TAAC. The Reb1p DNA
      structure does not show the conformational mobility or the 'transient kink' at
      TpA steps characteristic of the related TAAT-containing sequences.

PMID- 9016610
TI  - Activated levels of rRNA synthesis in fission yeast are driven by an intergenic
      rDNA region positioned over 2500 nucleotides upstream of the initiation site.
AB  - RNA polymerase I-catalyzed synthesis of the Schizosaccharomyces pombe
      approximately 37S pre-rRNAs was shown to be sensitive to regulatory sequences
      located several kilobases upstream of the initiation site for the rRNA gene. An
      in vitro transcription system for RNA polymerase I-catalyzed RNA synthesis was
      established that supports correct and activated transcription from templates
      bearing a full S. pombe rRNA gene promoter. A 780 bp region starting at -2560
      significantly stimulates transcription of ac is-located rDNA promoter and
      competes with an rDNA promoter in trans, thus displaying some of the activities
      of rDNA transcriptional enhancers in vitro. Deletion of a 30 bp enhancer
      homologous domain in this 780 bp far upstream region blocked its cis-stimulatory
      effect. The sequence of the S. pombe 3.5 kb intergenic spacer was determined and
      its organization differs from that of vertebrate, Drosophila, Acanthamoeba and
      plant intergenic rDNA spacers: it does not contain multiple, imperfect copies of
      the rRNA gene promoter nor repetitive elements of 140 bp, as are found in
      vertebrate rDNA enhancers.

PMID- 9016613
TI  - Sequencing double-stranded DNA by strand displacement.
AB  - Duplex probes with five base single-stranded overhangs can capture dsDNA targets
      from type IIS restriction nuclease digests. Ligation generates a predesigned nick
      site, where DNA polymerase can generate sequencing ladders by strand displacement
      or nick translation in the presence of trace amounts of dideoxynucleotides. This
      allows dsDNA targets to be captured from mixtures and directly sequenced without
      subcloning, purification or denaturation.

PMID- 9016612
TI  - An effective method of RNA extraction from bacteria refractory to disruption,
      including mycobacteria.
AB  - A high yield, rapid and simple procedure is described for extracting RNA from
      mycobacteria and other micro-organisms refractory to disruption. The method
      yielded 20 microg RNA/109 Mycobacterium bovis BCG, more than 10 times greater
      than our previous method. Intact full length hsp 70 (dnaK) mRNA was detected by
      northern blotting and quantitated after heat shock by slot blot hybridisation.

PMID- 9016614
TI  - An ELISA for detection of apoptosis.
AB  - We describe a simple and convenient enzyme-linked immunosorbent assay (ELISA) for
      the detection of apoptosis in tissue culture. An early event in apoptosis is DNA
      fragmentation followed by release of nucleosomes into the cytoplasm. Our sandwich
      assay uses a pair of monoclonal antibodies specific for two nucleosomal epitopes
      to capture and detect cytoplasmic nucleosomes onto the ELISA plate. Our assay is
      about 500 times more sensitive than the detection of apoptotic DNA ladder by
      agarose electrophoresis and is especially suited for the testing of large numbers
      of samples.

PMID- 9016615
TI  - High efficiency of site-directed mutagenesis mediated by a single PCR product.
AB  - We describe a highly efficient procedure for site-specific mutagenesis of double
      stranded plasmids. The method relies on a single PCR primer which incorporates
      both the mutations at the selection site and the desired single base
      substitutions at the mutant site. This primer is annealed to the denatured
      plasmid and directs the synthesis of the mutant strand. After digestion with
      selection enzyme, the plasmid DNA is amplified into Escherichia coli strain BMH71
      18 and subjected to a second digestion and amplification into the bacterial
      strain DH5alpha. A mutagenesis efficiency >80% was consistently achieved in the
      case of two unrelated plasmids.

PMID- 9016616
TI  - Mutational spectrometry without phenotypic selection: human mitochondrial DNA.
AB  - By first separating mutant from nonmutant DNA sequences on the basis of their
      melting temperatures and then increasing the number of copies by high-fidelity
      DNA amplification, we have developed a method that allows observation of point
      mutations in biological samples at fractions at or above 10-6. Using this method,
      we have observed the hotspot point mutations that lie in 100 base pairs of the
      mitochondrial genome in samples of cultured cells and human tissues. To date, 19
      mutants have been isolated, their fractions ranging from 4x10-4 down to the limit
      of detection. We performed specific tests to determine if the observed signals
      were artefacts arising from contamination, polymerase errors during PCR or DNA
      adducts created during the procedure. We also tested the possibilities that DNA
      replication mismatch intermediates, or endogenous DNA adducts that were
      originally present in the cells, were included with true mutants in our
      separation steps and converted to mutants during PCR. We show that while most of
      the mutants behave as double-stranded point mutants in the cells, some appear to
      arise at least in part from mismatch intermediates or cellular DNA adducts. This
      technology is therefore sufficient for the observation of the spectrum of point
      mutations in human mitochondrial DNA and is a tool for discovering the primary
      causes of these mutations.

PMID- 9016617
TI  - Heat-shock inactivation of the TFIIH-associated kinase and change in the
      phosphorylation sites on the C-terminal domain of RNA polymerase II.
AB  - The C-terminal domain (CTD) of the RNA polymerase II largest subunit (RPB1) plays
      a central role in transcription. The CTD is unphosphorylated when the polymerase
      assembles into a preinitiation complex of transcription and becomes heavily
      phosphorylated during promoter clearance and entry into elongation of
      transcription. A kinase associated to the general transcription factor TFIIH, in
      the preinitiation complex, phosphorylates the CTD. The TFIIH-associated CTD
      kinase activity was found to decrease in extracts from heat-shocked HeLa cells
      compared to unstressed cells. This loss of activity correlated with a decreased
      solubility of the TFIIH factor. The TFIIH-kinase impairment during heat-shock was
      accompanied by the disappearance of a particular phosphoepitope (CC-3) on the
      RPB1 subunit. The CC-3 epitope was localized on the C-terminal end of the CTD and
      generated in vitro when the RPB1 subunit was phosphorylated by the TFIIH
      associated kinase but not by another CTD kinase such as MAP kinase. In apparent
      discrepancy, the overall RPB1 subunit phosphorylation increased during heat
      shock. The decreased activity in vivo of the TFIIH kinase might be compensated by
      a stress-activated CTD kinase such as MAP kinase. These results also suggest that
      heat-shock gene transcription may have a weak requirement for TFIIH kinase
      activity.

PMID- 9016618
TI  - Comparative analysis of the genomes of the bacteria Mycoplasma pneumoniae and
      Mycoplasma genitalium.
AB  - The sequenced genomes of the two closely related bacteria Mycoplasma genitalium
      and Mycoplasma pneumoniae were compared with emphasis on genome organization and
      coding capacity. All the 470 proposed open reading frames (ORFs) of the smaller
      M.genitalium genome (580 kb) were contained in the larger genome (816 kb) of
      M.pneumoniae. There were some discrepancies in annotation, but inspection of the
      DNA sequences showed that the corresponding DNA was always present in M.
      pneumoniae. The two genomes could be subdivided into six segments. The order of
      orthologous genes was well conserved within individual segments but the order of
      these segments in both bacteria was different. We explain the different
      organization of the segments by translocation via homologous recombination. The
      translocations did not disturb the continuous bidirectional course of
      transcription in both genomes, starting at the proposed origin of replication.
      The additional 236 kb in M.pneumoniae,compared with theM.genitalium genome, were
      coding for 209 proposed ORFs not identified in M.genitalium. Of these ORFs, 110
      were specific to M.pneumoniae exhibiting no significant similarity to
      M.genitalium ORFs, while 76 ORFs were amplifications of ORFs existing mainly as
      single copies in M. genitalium. In addition, 23 ORFs containing a copy of either
      one of the three repetitive DNA sequences RepMP2/3, RepMP4 and RepMP5 were
      annotated in M.pneumoniae but not in M.genitalium,although similar DNA sequences
      were present. TheM.pneumoniae-specific genes included a restriction-modification
      system, two transport systems for carbohydrates, the complete set of three genes
      coding for the arginine dihydrolase pathway and 14 copies of the repetitive DNA
      sequence RepMP1 which were part of several different translated genes with
      unknown function.

PMID- 9016619
TI  - DNA flexibility of the UP element is a major determinant for transcriptional
      activation at the Escherichia coli acetate promoter.
AB  - The specific interaction of the upstream element-containing promoter of the
      Escherichia coli acetate operon with either the RNA polymerase holoenzyme or its
      alpha subunit has been analyzed by the base removal method. Our results indicate
      that: (i) direct and specific base contacts can be detected in the acetate
      promoter-alpha subunit complex; (ii) base elimination in the upstream element of
      the acetate promoter enhances the binding of RNA polymerase. A similar effect is
      observed when studying the interactions between RNA polymerase and the rrnB
      ribosomal operon P1 promoter.

PMID- 9016620
TI  - Characterization of a RecA/RAD51 homologue from the hyperthermophilic archaeon
      Pyrococcus sp. KOD1.
AB  - The Pk-rec gene, encoding a RecA/RAD51 homologue from the hyperthermophilic
      archaeon Pyrococcussp. KOD1, was expressed in Escherichia coli. The recombinant
      Pk-REC was purified to homogeneity and was shown to be in a dimeric form. A
      striking property of the purified recombinant Pk-REC was the unusual DNase
      activity on both single- and double-stranded DNAs along with the ATPase activity.
      The reaction product of this DNase activity was mononucleotides. The optimum
      temperature and pH for the DNase activity were 60 degrees C and 8-8.5,
      respectively. In addition, the metal ion requirement for DNase activity was
      different from that for the ATPase activity. The protein exhibited no DNase
      activity in the presence of Zn2+ion, which was one of the most preferable
      divalent cations for ATPase activity. Another unique characteristic of the
      recombinant protein was that the reaction product of ATPase activity was AMP
      instead of ADP.Pk-REC may represent a common prototype of the RecA family
      proteins with high RecA-like activity.

PMID- 9016621
TI  - Domain structure of vaccinia DNA ligase.
AB  - The 552 amino acid vaccinia virus DNA ligase consists of three structural domains
      defined by partial proteolysis: (i) an amino-terminal 175 amino acid segment that
      is susceptible to digestion with chymotrypsin and trypsin; (ii) a protease
      resistant central domain that contains the active site of nucleotidyl transfer
      (Lys-231); (iii) a protease-resistant carboxyl domain. The two protease-resistant
      domains are separated by a protease-sensitive interdomain bridge from positions
      296 to 307. Adenylyltransferase and DNA ligation activities are preserved when
      the N-terminal 200 amino acids are deleted. However, the truncated form of
      vaccinia ligase has a reduced catalytic rate in strand joining and a lower
      affinity for DNA than does the full-sized enzyme. The 350 amino acid catalytic
      core of the vaccinia ligase is similar in size and protease-sensitivity to the
      full-length bacteriophage T7 DNA ligase.

PMID- 9016622
TI  - Cleavage properties of an estrogen-regulated polysomal ribonuclease involved in
      the destabilization of albumin mRNA.
AB  - Previous work from this laboratory [Dompenciel,R.E., Garnepudi,V.R. and
      Schoenberg,D.R. (1995)J. Biol. Chem.270, 6108-6118] described the purification
      and properties of an estrogen-regulated endonuclease isolated from Xenopus liver
      polysomes that is involved in the destabilization of albumin mRNA. The present
      study mapped cleavages made by this enzyme onto the secondary structure of the
      portion of albumin mRNA bearing the major cleavage sites. The predominant
      cleavages occur in the overlapping APyrUGA sequence AUUGACUGA present in a single
      stranded loop region, and in AUUGA located within a bulged AU-rich stem. A
      structural mutation which converted the major loop cleavage site to a hairpin
      bearing one APyrUGA element eliminated cleavage at the intact site. This confirms
      that the polysomal RNase is specific for single-stranded RNA. Additional point
      mutations in the major loop characterized the nucleoside sequence requirements
      for cleavage. Finally, snake venom exonuclease was used to demonstrate the
      polysomal RNase generates products with a 3' hydroxyl. Binding of an estrogen
      induced protein to a portion of the 3'UTR of vitellogenin mRNA may be involved in
      its stabilization by estrogen [Dodson,R.E. and Shapiro,D.J. (1994)Mol. Cell.
      Biol.14, 3130-3138]. The core binding site for this protein bears the sequence
      APyrUGA, suggesting that stabilization may be accomplished by occlusion of a
      cleavage site for the polysomal RNase.

PMID- 9016623
TI  - The RAD5 gene product is involved in the avoidance of non-homologous end-joining
      of DNA double strand breaks in the yeast Saccharomyces cerevisiae.
AB  - In wild-type yeast, the repair of a 169 bp double-strand gap induced by the
      restriction enzymes ApaI and NcoI in the URA3gene of the shuttle vector YpJA18
      occurs with high fidelity according to the homologous chromosomal sequence. In
      contrast, only 25% of the cells of rad5-7 and rad5 Delta mutants perform correct
      gap repair. As has been proven by sequencing of the junction sites, the remaining
      cells recircularise the gapped plasmids by joining of the non-compatible, non
      homologous ends. Thus, regarding the repair of DNA double-strand breaks, the rad5
      mutants behave like mammalian cells rather than budding yeast. The majority of
      the end joined plasmids miss either one or both of the 3'and 5'protruding single
      strands of the restriction ends completely and have undergone blunt-end ligation
      accompanied by fill-in DNA synthesis. These results imply an important role for
      the Rad5 protein (Rad5p) in the protection of protruding single-strand ends and
      for the avoidance of non-homologous end joining during repair of double-strand
      gaps in budding yeast. Alternatively, the Rad5p may be an accessory factor
      increasing the efficiency of homologous recombination in yeast, however, the
      molecular mechanism of Rad5p function requires further investigation.

PMID- 9016624
TI  - Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative
      splicing and transcription from different positions in the UNG gene.
AB  - A distinct nuclear form of human uracil-DNA glycosylase [UNG2, open reading frame
      (ORF) 313 amino acid residues] from the UNG gene has been identified. UNG2
      differs from the previously known form (UNG1, ORF 304 amino acid residues) in the
      44 amino acids of the N-terminal sequence, which is not necessary for catalytic
      activity. The rest of the sequence and the catalytic domain, altogether 269 amino
      acids, are identical. The alternative N-terminal sequence in UNG2 arises by
      splicing of a previously unrecognized exon (exon 1A) into a consensus splice site
      after codon 35 in exon 1B (previously designated exon 1). The UNG1 sequence
      starts at codon 1 in exon 1B and thus has 35 amino acids not present in UNG2.
      Coupled transcription/translation in rabbit reticulocyte lysates demonstrated
      that both proteins are catalytically active. Similar forms of UNG1 and UNG2 are
      expressed in mouse which has an identical organization of the homologous gene.
      Constructs that express fusion products of UNG1 or UNG2 and green fluorescent
      protein (EGFP) were used to study the significance of the N-terminal sequences in
      UNG1 and UNG2 for subcellular targeting. After transient transfection of HeLa
      cells, the pUNG1-EGFP-N1 product colocalizes with mitochondria, whereas the pUNG2
      EGFP-N1 product is targeted exclusively to nuclei.

PMID- 9016625
TI  - The activation domain of the maize transcription factor Opaque-2 resides in a
      single acidic region.
AB  - The maize (Zea mays L.) endosperm specific transcription factor, encoded by the
      Opaque-2(O2) locus, functions in vivo to activate transcription from its target
      promoters.O2 regulates the expression of a major storage protein class, the 22
      kDa zeins, and of a type I ribosome inactivating protein, b-32, during maturation
      phase endosperm development. The coding sequence of O2, which indicates it to be
      a member of the basic region-leucine zipper (bZIP) class of DNA-binding proteins,
      contains a number of regions rich in either proline or acidic residues which are
      candidates for activation domains. In functional assays using tobacco mesophyll
      protoplasts, the level of transactivation conferred by a series of O2-deletion
      constructs was tested using as a reporter a fusion of the b-32 target promoter to
      beta-glucuronidase (GUS). The results indicate that O2 has a single acidic
      activation domain, located near the N-terminus of the protein (amino acids 41
      91). The ability of a shorter part of this domain (amino acids 39-82) to confer
      transactivation was also demonstrated in domain swapping experiments, using
      fusions of the O2 polypeptide sequence to the DNA-binding domain of the parsley
      (Petroselinum crispum) transcription factor CPRF1.

PMID- 9016626
TI  - Flavin adenine dinucleotide as a chromophore of the Xenopus (6-4)photolyase.
AB  - Two types of enzyme utilizing light from the blue and near-UV spectral range (320
      520 nm) are known to have related primary structures: DNA photolyase, which
      repairs UV-induced DNA damage in a light-dependent manner, and the blue light
      photoreceptor of plants, which mediates light-dependent regulation of seedling
      development. Cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone
      photoproducts [(6-4)photoproducts] are the two major photoproducts produced in
      DNA by UV irradiation. Two types of photolyases have been identified, one
      specific for CPDs (CPD photolyase) and another specific for (6-4)photoproducts
      [(6-4)photolyase]. (6-4)Photolyase activity was first found in Drosophila
      melanogaster and to date this gene has been cloned only from this organism. The
      deduced amino acid sequence of the cloned gene shows that (6-4)photolyase is a
      member of the CPD photolyase/blue light photoreceptor family. Both CPD photolyase
      and blue light photoreceptor are flavoproteins and bound flavin adenine
      dinucleotides (FADs) are essential for their catalytic activity. Here we report
      isolation of a Xenopus laevis(6-4)photolyase gene and show that the (6
      4)photolyase binds non- covalently to stoichiometric amounts of FAD. This is the
      first indication of FAD as the chromophore of (6-4)photolyase.

PMID- 9016627
TI  - The subcellular localization and length of hammerhead ribozymes determine
      efficacy in human cells.
AB  - The length requirements of the antisense portion of hammerhead ribozymes for
      efficacy in living cells was investigated. The HIV-1tat-directed asymmetric
      hammerhead ribozyme alphaYRz195 was used with a 195 nt 3'-antisense arm and a 3
      nt 5'-antisense portion as well as a set of successively 3'-shortened derivatives
      thereof. In the 3'-antisense arm a minimum length of 20 complementary nucleotides
      was required for efficient association with a 645 nt target RNA transcript in
      vitro(for all constructs kass ranged between 0.3 and 1.8x104/M/s). The cleavage
      rate constants (kcleav) were independent of the length of the antisense flank and
      ranged between 0.8 and 1.2x10-4/s. However, the length of the antisense arms, as
      well as the mode of delivery and the subcellular location of the ribozymes, had a
      dramatic effect on efficacy in HIV-1-producing human cells. When proviral HIV-1
      DNA and ribozymes were co-microinjected into the nucleus of human cells, a
      minimum length of 51 nt in the antisense arm was necessary for antisense- and
      ribozyme-mediated inhibition of HIV-1 replication. Ribozymes with shorter
      antisense arms were almost ineffective. Conversely, short chain ribozymes,
      including those with chemical modifications, were superior to long chain
      ribozymes when co-microinjected into the cytoplasm. When transfected, all
      ribozymes showed an antisense effect as well as an additional ribozyme-mediated
      increase in inhibition. Consequences for the design and application of ribozymes
      are discussed.

PMID- 9016628
TI  - RNase H-independent antisense activity of oligonucleotide N3 '--> P5 '
      phosphoramidates.
AB  - Oligonucleotide N3'-->P5'phosphoramidates are a new and promising class of
      antisense agents. Here we report biological properties of phosphoramidate
      oligonucleotides targeted against the human T cell leukemia virus type-I Tax
      protein, the major transcriptional transactivator of this human retrovirus.
      Isosequential phosphorothioate oligodeoxynucleotides and uniformly modified and
      chimeric phosphoramidate oligodeoxynucleotides containing six central
      phosphodiester linkages are all quite stable in cell nuclei. The uniformly
      modified anti-tax phosphoramidate oligodeoxynucleotide does not activate nuclear
      RNase H, as was shown by RNase protection assay. In contrast, the chimeric
      phosphoramidate-phosphodiester oligodeoxynucleotide is an efficient activator of
      RNase H. The presence of one or two mismatched nucleotides in the phosphodiester
      portion of oligonucleotides affected this activation only negligibly. When
      introduced into tax-transformed fibroblasts ex vivo, only the uniformly modified
      anti-tax phosphoramidate oligodeoxynucleotide caused a sequence-dependent
      reduction in the Tax protein level. Neither the chimeric phosphoramidate nor the
      phosphorothioate oligodeoxynucleotides significantly reduced tax expression under
      similar experimental conditions.

PMID- 9016629
TI  - Libraries for genomic SELEX.
AB  - An increasing number of proteins are being identified that regulate gene
      expression by binding specific nucleic acidsin vivo. A method termed genomic
      SELEX facilitates the rapid identification of networks of protein-nucleic acid
      interactions by identifying within the genomic sequences of an organism the
      highest affinity sites for any protein of the organism. As with its progenitor,
      SELEX of random-sequence nucleic acids, genomic SELEX involves iterative binding,
      partitioning, and amplification of nucleic acids. The two methods differ in that
      the variable region of the nucleic acid library for genomic SELEX is derived from
      the genome of an organism. We have used a quick and simple method to construct
      Escherichia coli, Saccharomyces cerevisiae, and human genomic DNA PCR libraries
      that can be transcribed with T7 RNA polymerase. We present evidence that the
      libraries contain overlapping inserts starting at most of the positions within
      the genome, making these libraries suitable for genomic SELEX.

PMID- 9016630
TI  - RNA polymerase II stalled at a thymine dimer: footprint and effect on excision
      repair.
AB  - Bulky lesions in the template strand block the progression of RNA polymerase II
      (RNAP II) and are repaired more rapidly than lesions in the non-transcribed
      strand, which do not block transcription. In order to better understand the basis
      of this transcription-coupled repair we developed an in vitro system with
      purified transcription and nucleotide excision repair proteins and a plasmid
      containing the adenovirus major late promoter and a thymine dimer in the template
      strand downstream of the transcription start site. The footprint of RNAP II
      stalled at the thymine dimer, obtained using DNase I, lambda exonuclease and T4
      polymerase 3'-->5'exonuclease, covers approximately 40 nt and is nearly
      symmetrical around the dimer. The ternary complex formed at the lesion site is
      rather stable, with a half-life of approximately 20 h. Surprisingly, addition of
      human repair proteins results in repair of transcription-blocking dimers in the
      ternary complex. The blocked polymerase neither inhibits nor stimulates repair
      and repair is observed in the absence of CSB protein, the putative human
      transcription-repair coupling factor.

PMID- 9016631
TI  - Transcriptional regulation of the Drosophila-raf proto-oncogene by the DNA
      replication-related element (DRE)/DRE-binding factor (DREF) system.
AB  - The DRE/DREF system plays an important role in transcription of DNA replication
      genes such as those encoding the 180 and 73 kDa subunits of DNA polymerase alpha
      as well as that for encoding PCNA. In this study, we found two sequences
      homologous to DRE (5'-TATCGATA-3') in the 5'-flanking region (-370 to -357 with
      respect to the transcription initiation site) of the D-raf gene and confirmed
      transcriptional activity through gel mobility shift assays, transient CAT assays,
      and spatial patterns of lacZ expression in transgenic larval tissues carrying D
      raf and lacZ fusion genes. Further, we demonstrated that the D-raf gene is
      another target of the Zerknullt (Zen) protein with observation of D-raf
      repression by Zen protein in cultured cells and its ectopic expression in the
      dorsal region of the homozygous zen mutant embryo. The evidence of DRE/DREF
      involvement in regulation of the D-raf gene obtained in this study strongly
      supports the idea that the DRE/DREF system is responsible for the coordinated
      regulation of cell proliferation-related genes in Drosophila.

PMID- 9016632
TI  - DNA sequencing using differential extension with nucleotide subsets (DENS).
AB  - Here we describe template directed enzymatic synthesis of unique primers,
      avoiding the chemical synthesis step in primer walking. We have termed this
      conceptually new technique DENS (differential extension with nucleotide subsets).
      DENS works by selectively extending a short primer, making it a long one at the
      intended site only. The procedure starts with a limited initial extension of the
      primer (at 20-30 degrees C) in the presence of only two out of the four possible
      dNTPs. The primer is extended by 6-9 bases or longer at the intended priming
      site, which is deliberately selected, (as is the two-dNTP set), to maximize the
      extension length. The subsequent termination reaction at 60-65 degrees C then
      accepts the extended primer at the intended site, but not at alternative sites,
      where the initial extension (if any) is generally much shorter. DENS allows the
      use of primers as long as 8mers (degenerate in two positions) which prime much
      more strongly than modular primers involving 5-7mers and which (unlike the
      latter) can be used with thermostable polymerases, thus allowing cycle-sequencing
      with dye-terminators compatible with Taq DNA polymerase, as well as making double
      stranded DNA sequencing more robust.

PMID- 9016633
TI  - Hairpin-dimer equilibrium of a parallel-stranded DNA hairpin: formation of a four
      stranded complex.
AB  - The 24mer deoxyoligonucleotide 3'-d(T)10-5'-5'-d(C)4- d(A)10-3'(psC4) with an
      uncommon 5'-p-5'phosphodiester linkage was designed to enable the formation of a
      hairpin structure with unusual parallel-stranded stem. As reference hairpin
      structure with an antiparallel-stranded stem, the 24mer 5'-d(T)10-d(C)4-d(A)10
      3'(apsC4) was chosen. The behaviour of these oligonucleotides at different
      temperatures, DNA and salt concentrations was characterised by a combination of
      UV melting, CD, CD melting, infrared and Raman spectroscopy, infrared melting and
      analytical ultracentrifugation. The parallel-stranded hairpin structure was found
      to be formed by psC4 only under conditions of low DNA concentration and low salt
      concentration. Increase of the NaCl concentration beyond the physiological level
      or high DNA concentration supports the formation of intermolecular multi-stranded
      structures. The experimental data are in agreement with a four-stranded complex
      formed by two molecules of psC4. The base pairing model of this asymmetric four
      stranded complex is based on the pyrimidine motif of a triple helix with two
      bifurcated hydrogen bonds at the O4 of the thymine each directed towards one of
      the amino protons of both adenines. In contrast, the reference oligonucleotide
      apsC4 forms only an antiparallel-stranded hairpin under all experimental
      conditions.

PMID- 9016634
TI  - Hydration effects on the duplex stability of phosphoramidate DNA-RNA oligomers.
AB  - Recent studies on uniformly modified oligonucleotides containing 3'-NHP(O)(O-)O
      5'internucleoside linkages (3'amidate) and alternatively modified
      oligonucleotides containing 3'-O(O-)(O)PNH-5'internucleoside linkages (5'amidate)
      have shown that 3'amidate duplexes, formed with DNA or RNA complementary strands,
      are more stable in water than those of the corresponding phosphodiesters. In
      contrast, 5'amidates do not form duplexes at all. There is no steric reason that
      the 5'amidate duplex should not form. We demonstrate that these differences arise
      from differential solvation of the sugar-phosphate backbones. By molecular
      dynamics calculations on models of 10mer single-stranded DNA and double-stranded
      DNA-RNA molecules, both with and without the phosphoramidate backbone
      modifications, we show that the single-stranded 3'amidate and 5'amidate backbones
      are equally well solvated, but the 5'amidate backbone is not adequately solvated
      in an A-form duplex. These results are supported by quantum chemical free energy
      of solvation calculations which show that the 3'amidate backbone is favored
      relative to the 5'amidate backbone.

PMID- 9016635
TI  - The effect of cross-links on the conformational dynamics of duplex DNA.
AB  - The base pair lifetimes and apparent dissociation constants of a 21 base DNA
      hairpin and an analog possessing a disulfide cross-link bridging the 3'- and 5'
      terminal bases were determined by measuring imino proton exchange rates as a
      function of exchange catalyst concentration and temperature. A comparison of the
      lifetimes and apparent dissociation constants for corresponding base pairs of the
      two hairpins indicates that the cross-link neither increases the number of base
      pairs involved in fraying nor alters the lifetime, dissociation constant, or the
      opened structure from which exchange occurs for the base pairs that are not
      frayed. The cross-link does, however, stabilize the frayed penultimate base pair
      of the stem duplex. Significantly, it appears that the disulfide cross-link is
      more effective at preventing fraying of the penultimate base pair than is the 5
      base hairpin loop. Because this disulfide cross-link can be incorporated site
      specifically, and does not adversely affect static or dynamic properties of DNA,
      it should prove very useful in studies of nucleic acid structure and function.

PMID- 9016636
TI  - Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the
      multifunctional transcription factor YY1.
AB  - Muscle-restricted transcription of sarcomeric actin genes is negatively
      controlled by the zinc finger protein YY1, which is down-regulated at the protein
      level during myogenic differentiation. To identify cellular proteins that might
      mediate the function/stability of YY1 in muscle cells, we screened an adult human
      muscle cDNA library using the yeast two-hybrid cloning system. We report the
      isolation and characterization of a novel protein termed YAF2 (YY1- associated
      factor 2) that interacts with YY1. The YAF2 cDNA encodes a 180 amino acid basic
      protein (pI 10.5) containing a single N-terminal C2-X10-C2 zinc finger. Lysine
      clusters are present that may function as a nuclear localization signal. Domain
      mapping analysis shows that the first and second zinc fingers of YY1 are targeted
      for YAF2 protein interaction. In contrast to the down-regulation of YY1, YAF2
      message levels increase during in vitro differentiation of both rat skeletal and
      cardiac muscle cells. YAF2 appears to have a promyogenic regulatory role, since
      overexpression of YAF2 in C2 myoblasts stimulates myogenic promoter activity
      normally restricted by YY1. Co-transfection of YY1 reverses the stimulatory
      effect of YAF2. YAF2 also greatly potentiates proteolytic cleavage of YY1 by the
      calcium- activated protease m-calpain. The isolation of YAF2 may help in
      understanding the mechanisms through which inhibitors of myogenic transcription
      may be antagonized or eliminated by proteolysis during muscle development.

PMID- 9016637
TI  - Quantitative analysis of electrophoresis data: novel curve fitting methodology
      and its application to the determination of a protein-DNA binding constant.
AB  - A computer program, GelExplorer, which uses a new methodology for obtaining
      quantitative information about electrophoresis has been developed. It provides a
      straightforward, easy-to-use graphical interface, and includes a number of
      features which offer significant advantages over existing methods for
      quantitative gel analysis. The method uses curve fitting with a nonlinear least
      squares optimization to deconvolute overlapping bands. Unlike most curve fitting
      approaches, the data is treated in two dimensions, fitting all the data across
      the entire width of the lane. This allows for accurate determination of the
      intensities of individual, overlapping bands, and in particular allows
      imperfectly shaped bands to be accurately modeled. Experiments described in this
      paper demonstrate empirically that the Lorentzian lineshape reproduces the
      contours of an individual gel band and provides a better model than the Gaussian
      function for curve fitting of electrophoresis bands. Results from several fitting
      applications are presented and a discussion of the sources and magnitudes of
      uncertainties in the results is included. Finally, the method is applied to the
      quantitative analysis of a hydroxyl radical footprint titration experiment to
      obtain the free energy of binding of the lambda repressor protein to the OR1
      operator DNA sequence.

PMID- 9016638
TI  - Splicing efficiency of human immunodeficiency virus type 1 tat RNA is determined
      by both a suboptimal 3' splice site and a 10 nucleotide exon splicing silencer
      element located within tat exon 2.
AB  - We have previously demonstrated that an exon splicing silencer (ESS) is present
      within human immunodeficiency virus type 1 (HIV-1)tat exon 2. This 20 nucleotide
      (nt) RNA element acts selectively to inhibit splicing at the upstream 3'splice
      site (3'ss #3) flanking this exon. In this report, we have used in vitro splicing
      of mutated RNA substrates to determine the sequences necessary and sufficient for
      the activity of the ESS. The activity of the ESS within tat exon 2 maps to a 10
      nt core sequence CUAGACUAGA. This core sequence was sufficient to inhibit
      splicing when inserted downstream from the 3'ss of the heterologous Rous sarcoma
      virus src gene. Mutagenesis of the interspersed purines in the polypyrimidine
      tract of the tat exon 2 3'ss to pyrimidines resulted in a significant increase in
      splicing efficiency indicating that 3'ss#3 is suboptimal. The ESS acts to inhibit
      splicing at the optimized 3'splice sites of both the HIV-1 tat and RSV src
      constructs but with a reduced efficiency compared to its effect on suboptimal
      3'splice sites. The results indicate that both the ESS and a suboptimal 3'splice
      site act together to control splicing at the 3'splice site flanking at exon 2.

PMID- 9016639
TI  - Targeted integration of DNA using mutant lox sites in embryonic stem cells.
AB  - Site-directed DNA integration has been achieved by using a pair of mutant lox
      sites, a right element (RE) mutant lox site and a left element (LE) mutant lox
      site [Albertet al. (1995)Plant J., 7, 649-659], in mouse embryonic stem (ES)
      cells. We established ES cell lines carrying a single copy of the wild-type lox
      Por LE mutant lox site as a target and examined the frequency of site-specific
      integration of a targeting vector carrying a loxP or RE mutant lox site induced
      by Cre transient expression. Since our targeting vector contains a complete neo
      gene, random integrants can form colonies as in the case of a gene targeting
      event through homologous recombination. With our system, the frequency of site
      specific integration via the mutant lox sites reached a maximum of 16%. In
      contrast, the wild-type loxP sites yielded very low frequencies (<0.5%) of site
      specific integration events. This mutatedloxsystem will be useful for 'knock-in'
      integration of DNA in ES cells.

PMID- 9016640
TI  - Atomic force microscopic demonstration of DNA looping by GalR and HU.
AB  - Regulation of gene transcription in both prokaryotes and eukaryotes involves
      formation of various DNA-multiprotein complexes of higher order structure through
      communication between distant regions of DNA. The communication between distant
      DNA sites occurs by interaction between proteins bound to the sites by looping
      out the intervening DNA segments. The repression of transcription of two
      overlapping promoters of the gal operon in Escherichia coli requires Gal
      repressor (GalR) and the histone-like protein HU. Both in vivo and in vitro data
      support a proposed HU containing complex responsive to induction in which GalR
      molecules bound to two distant operator sites interact by looping out DNA. We
      successfully applied atomic force microscope (AFM) imaging to visualize galDNA
      complexes with proteins. We report GalR mediated DNA looping in which HU plays an
      obligatory role by helping GalR tetramerization. Supercoiling of DNA, which is
      also critical for GalR action, may stabilize the DNA loops by providing an
      energetically favorable geometry of the DNA.

PMID- 9016641
TI  - Phosphorylation of ATF-1 enhances its DNA binding and transcription of the Na,K
      ATPase alpha 1 subunit gene promoter.
AB  - Transcriptional activity of both ATF-1 and CREB is enhanced by protein
      phosphorylation. While enhancement has been attributed to an increase in binding
      affinity for a co-activator (CBP), induction of the DNA binding activity by
      phosphorylation is an open question. Using the Na,K-ATPase alpha1 subunit gene
      promoter, which has an asymmetrical ATF/CRE site, we analyzed the effect of
      phosphorylation on DNA binding activity of the ATF-1-CREB heterodimer.
      Dephosphorylation of the heterodimer in nuclear extracts reduced binding to the
      ATF/CRE site. Phosphorylation of ATF-1 at Ser63 enhanced its binding to the
      ATF/CRE site in both the homodimeric and heterodimeric forms. Transcription of
      the Na,K-ATPase alpha 1 subunit gene promoter was also stimulated by
      phosphorylated ATF-1 in vitro.

PMID- 9016642
TI  - Radioprobing of DNA: distribution of DNA breaks produced by decay of 125I
      incorporated into a triplex-forming oligonucleotide correlates with geometry of
      the triplex.
AB  - The distribution of breaks produced in both strands of a DNA duplex by the decay
      of 125I carried by a triplex-forming DNA oligonucleotide was studied at single
      nucleotide resolution. The 125I atom was located in the C5 position of a single
      cytosine residue of an oligonucleotide designed to form a triple helix with the
      target sequence duplex. The majority of the breaks (90%) are located within 10 bp
      around the decay site. The addition of the free radical scavenger DMSO produces
      an insignificant effect on the yield and distribution of the breaks. These
      results suggest that the majority of these breaks are produced by the direct
      action of radiation and are not mediated by diffusible free radicals. The
      frequency of breaks in the purine strand was two times higher that in the
      pyrimidine strand. This asymmetry in the yield of breaks correlates with the
      geometry of this type of triplex; the C5 of the cytosine in the third strand is
      closer to the sugar-phosphate backbone of the purine strand. Moreover, study of
      molecular models shows that the yield of breaks at individual bases correlates
      with distance from the 125I decay site. We suggest the possible use of 125I decay
      as a probe for the structure of nucleic acids and nucleoprotein complexes.

PMID- 9016644
TI  - Rearrangement of interstrand cross-links into intrastrand cross-links in cis
      diamminedichloroplatinum(II)-modified DNA.
AB  - In the reaction of the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP)
      with DNA, bifunctional intrastrand and interstrand cross-links are formed. In
      this work, we show that at 37 degrees C interstrand cross-links (ICL) are labile
      and rearrange into intrastrand cross-links. The ICL instability was first studied
      with a 10 base pairs (bp) double-stranded oligonucleotide containing a unique
      site-specific ICL resulting from chelation of the N7 position of two guanine
      residues on the opposite strands of DNA at the d(GC/GC) site by a cis
      diammineplatinum(II) residue. The bonds between the platinum and the N7 of
      guanine residues within the interstrand adduct are cleaved. In 50 mM NaCl or
      NaClO4, this cleavage results in the formation of monofunctional adducts which
      subsequently form intrastrand cross-links. One cleavage reaction takes place per
      cross-linked duplex in either of both DNA strands. Whereas the starting cross
      linked 10 bp duplex is hydrogen bonded, the two complementary DNA strands
      separate after the cleavage of the ICL. Under these conditions, the cleavage
      reaction is irreversible allowing its rate measurement (t1/2= 29+/-2 h) and
      closure of monofunctional adducts to intrastrand cross-links occurs within single
      stranded DNA. Within a longer cross-linked oligonucleotide (20 bp), ICL are
      apparently more stable (t1/2= 120+/-12 h) as a consequense of monofunctional
      adducts closure back to ICL. We propose that the ICL cleavage is reversible in
      DNA and that these adducts rearrange finally into intrastrand cross-links. Our
      results could explain an 'ICL unhooking' in previously reported in vivo repair
      studies [Zhenet al. (1993)Carcinogenesis14, 919-924].

PMID- 9016643
TI  - Functional analysis of the polypyrimidine tract in pre-mRNA splicing.
AB  - The polypyrimidine tract is one of the important cis-acting sequence elements
      directing intron removal in pre-mRNA splicing. Progressive deletions of the
      polypyrimidine tract have been found to abolish correct lariat formation,
      spliceosome assembly and splicing. In addition, the polypyrimidine tract can
      alter 3'-splice site selection by promoting alternative branch site selection.
      However, there appears to be great flexibility in the specific sequence of a
      given tract. Not only the optimal composition of the polypyrimidine tract, but
      also the role of the tract in introns with no apparent polypyrimidine tracts or
      where changes in the tract are apparently harmless are uncertain. Accordingly, we
      have designed a series of cis-competition splicing constructs to test the
      functional competitive efficiency of a variety of systematically mutated
      polypyrimidine tracts. An RT/PCR assay was used to detect spliced product
      formation as a result of differential branch point selection dependent on direct
      competition between two opposing polypyrimidine tracts. We found that pyrimidine
      tracts containing 11 continuous uridines are the strongest pyrimidine tracts. In
      such cases, the position of the uridine stretch between the branch point and 3'
      splice site AG is unimportant. In contrast, decreasing the continuous uridine
      stretch to five or six residues requires that the tract be located immediately
      adjacent to the AG for optimal competitive efficiency. The block to splicing with
      decreasing polypyrimidine tract strength is primarily prior to the first step of
      splicing. While lengthy continuous uridine tracts are the most competitive,
      tracts with decreased numbers of consecutive uridines and even tracts with
      alternating purine/pyrimidine residues can still function to promote branch point
      selection, but are far less effective competitors in 3'-splice site selection
      assays.

PMID- 9016645
TI  - Molecular cloning and analysis of Schizosaccharomyces pombe Reb1p: sequence
      specific recognition of two sites in the far upstream rDNA intergenic spacer.
AB  - The coding sequences for a Schizosaccharomyces pombe sequence-specific DNA
      binding protein, Reb1p, have been cloned. The predicted S. pombe Reb1p is 24-29%
      identical to mouse TTF-1 (transcription termination factor-1) and Saccharomyces
      cerevisiae REB1 protein, both of which direct termination of RNA polymerase I
      catalyzed transcripts. The S.pombe Reb1 cDNA encodes a predicted polypeptide of
      504 amino acids with a predicted molecular weight of 58.4 kDa. The S. pombe Reb1p
      is unusual in that the bipartite DNA binding motif identified originally in
      S.cerevisiae and Klyveromyces lactis REB1 proteins is uninterrupted and thus
      S.pombe Reb1p may contain the smallest natural REB1 homologous DNA binding
      domain. Its genomic coding sequences were shown to be interrupted by two introns.
      A recombinant histidine-tagged Reb1 protein bearing the rDNA binding domain has
      two homologous, sequence-specific binding sites in the S. pomber DNA intergenic
      spacer, located between 289 and 480 nt downstream of the end of the approximately
      25S rRNA coding sequences. Each binding site is 13-14 bp downstream of two of the
      three proposed in vivo termination sites. The core of this 17 bp site,
      AGGTAAGGGTAATGCAC, is specifically protected by Reb1p in footprinting analysis.

PMID- 9016646
TI  - Covalent attachment of DNA oligonucleotides to glass.
AB  - A method for synthesizing DNA directly on glass is presented. The process is
      based on pretreatment of glass with boiling hydrochloric acid, thus exposing the
      hydroxyl groups of the glass. Phosphite-triester chemistry was used to directly
      attach the first nucleotide to a glass plate via a covalent bond between the
      hydroxyl group of the glass and the phosphate group of the protected
      deoxyribonucleotide. Standard molecular biology procedures, such as ligation and
      restriction digest, were efficiently performed on the glass synthesized
      oligonucleotide, with the added benefit of extreme ease of handling.

PMID- 9016647
TI  - Screening differentially expressed cDNA clones obtained by differential display
      using amplified RNA.
AB  - The major obstacle of differential display is not the technique itself but rather
      the post-differential display issueof discriminating between false positives and
      the truly differentially expressed mRNAs. This process is arduous and requires
      large amounts of RNA. We present and validate a method which allows one to screen
      putative positives from differential display analysis using only micrograms of
      total RNA. More importantly, we demonstrate that cDNA probes generated from
      amplified RNA are representative of the starting mRNA population and can be used
      for differential screening of mRNA species at a detectable limit of sensitivity
      of>/=1/40 000.

PMID- 9016649
TI  - Gene targeting in C57BL/6 ES cells. Successful germ line transmission using
      recipient BALB/c blastocysts developmentally matured in vitro.
AB  - There are significant advantages to the production of gene-knockout mice directly
      in mouse strains other than 129. The availability now of ES cells derived from
      the C57BL/6 mouse strain presents workers with a valuable alternative. A major
      difficulty, however, is the requirement for BALB/c blastocysts as recipients for
      ES cell injection. Using standard procedures, few BALB/c blastocysts can be
      obtained. This limitation has now been resolved by harvesting BALB/c embryos at
      the early morula stage and maturing these to blastocysts by in vitro culture. Of
      early morulae harvested and cultured, over 70% were recovered as fully expanded
      and injectable blastocysts. C57BL/6 ES cell injection of these blastocysts has
      enabled the production of a number of gene-knockout mice with a success rate
      similar to that reported for ES cells derived from the 129 mouse strains.

PMID- 9016648
TI  - Simultaneous display of different peptides on the surface of filamentous
      bacteriophage.
AB  - We have developed a new system for producing hybrid virions of filamentous
      bacteriophage fd simultaneously displaying two different peptides by infecting
      cells harbouring a plasmid containing a modified gene VIII with an engineered
      bacteriophage carrying a second and different copy of a modified gene VIII. The
      simultaneous display of different peptides has many potential applications in
      exploring the immune response and studying protein-protein interaction.

PMID- 9016650
TI  - Molecular basis of artifacts in the detection of telomerase activity and a
      modified primer for a more robust 'TRAP' assay.
AB  - Human somatic cells have essentially no telomerase activity. Telomerase is linked
      to tumor genesis and is a valuable marker for malignant growth. Extreme paucity
      of the enzyme neccessitated development of a PCR-based assay, 'telomeric repeat
      amplification protocol' (TRAP). Unfortunately, this method is not without
      difficulties. Amplification products are not related to the size of the amplified
      telomerase products. Furthermore, false positive results can occur, and careful
      control of reaction conditions is crucial. We analyzed in detail the molecular
      basis of artifacts. Based on these data, reverse PCR primer was changed and both
      problems in the TRAP assay were eliminated.

PMID- 9016651
TI  - Ligation mediated fluorescent labeling of DNA sequencing primers.
AB  - Automated DNA sequencing utilizing fluorescently labeled primers is a proven
      methodology for generating quality sequence data. However, for directed primer
      walking strategies this necessitates synthesis and labeling of a unique primer
      for each sequencing reaction. Here, we describe a rapid ligation-based method of
      generating labeled sequencing primers. An unlabeled 5'-phosphorylated sequencing
      primer is ligated to a fluorescent oligonucleotide by use of a bridge primer
      which is complementary to portions of the previous two oligonucleotides, thus
      aligning them properly for ligation. The resulting fluorescent hybrid primer can
      be utilized directly in cycle sequencing reactions without any prior
      purification.

PMID- 9016652
TI  - Deoxy- and dideoxynucleotide discrimination and identification of critical 5'
      nuclease domain residues of the DNA polymerase I from Mycobacterium tuberculosis.
AB  - The DNA polymerase I (PolI) from Mycobacterium tuberculosis (Mtb) was
      overproduced in Escherichia coli as an enzymatically active, recombinant protein
      with or without an N-terminal His-tag. The proteins catalysed both the DNA
      polymerisation of homo- and heteropolymer template-primers and the 5'-3'
      exonucleolytic hydrolysis of gapped and nicked substrates but lacked an
      associated proofreading activity. In accordance with recent predictions [Tabor,
      S. and Richardson, C.C. (1995) Proc. Natl. Acad. Sci. USA, 92, 6339-6343], both
      recombinant forms of the M. tuberculosis enzyme were unable to discriminate
      against dideoxynucleotide 5'-triphosphates and were thus efficiently inhibited by
      these chain-terminating nucleotide analogues during DNA synthesis. This unusual
      property might be potentially exploitable in terms of novel anti-mycobacterial
      drug design. A mutational analysis of 5' nuclease domain residues allowed the
      roles of nine invariant acidic residues to be evaluated. Acidic side chain
      neutralisation resulted in a > or = 20-fold reduction in activity, with the most
      profound reduction (> or = 10(4)-fold) being caused by neutralisation of the
      Asp125, Asp148 and Asp150 residues.

PMID- 9016653
TI  - High resolution footprinting of a type I methyltransferase reveals a large
      structural distortion within the DNA recognition site.
AB  - The type I DNA methyltransferase M.EcoR124I is a multi-subunit enzyme that binds
      to the sequence GAAN6RTCG, transferring a methyl group from S-adenosyl methionine
      to a specific adenine on each DNA strand. We have investigated the protein-DNA
      interactions in the complex by DNase I and hydroxyl radical footprinting. The
      DNase I footprint is unusually large: the protein protects the DNA on both
      strands for at least two complete turns of the helix, indicating that the enzyme
      completely encloses the DNA in the complex. The higher resolution hydroxyl
      radical probe shows a smaller, but still extensive, 18 bp footprint encompassing
      the recognition site. Within this region, however, there is a remarkably hyper
      reactive site on each strand. The two sites of enhanced cleavage are co-incident
      with the two adenines that are the target bases for methylation, showing that the
      DNA is both accessible and highly distorted at these sites. The hydroxyl radical
      footprint is unaffected by the presence of the cofactor S-adenosyl methionine,
      showing that the distorted DNA structure induced by M.EcoR124I is formed during
      the initial DNA binding reaction and not as a transient intermediate in the
      reaction pathway.

PMID- 9016654
TI  - Transcriptional repression by RING finger protein TIF1 beta that interacts with
      the KRAB repressor domain of KOX1.
AB  - Many of the vertebrate zinc finger factors of the Kruppel type (C2H2 zinc
      fingers) contain in their N-terminus a conserved sequence referred to as the KRAB
      (Kruppel-associated box) domain that, when tethered to DNA, efficiently represses
      transcription. Using the yeast two-hybrid system, we have isolated an 835 amino
      acid RING finger (C3HC4 zinc finger) protein, TIF1 beta (also named KAP-1), that
      specifically interacts with the KRAB domain of the human zinc finger factor
      KOX1/ZNF10. TIF1 beta, TIF1 alpha, PML and efp belong to a characteristic
      subgroup of RING finger proteins that contain one or two other Cys/His-rich
      clusters (B boxes) and a putative coiled-coil in addition to the classical C3HC4
      RING finger motif (RBCC configuration). Like TIF1 alpha, TIF1 beta also contains
      an additional Cys/His cluster (PHD finger) and a bromo-related domain. When
      tethered to DNA, TIF1 beta can repress transcription in transiently transfected
      mammalian cells both from promoter-proximal and remote (enhancer) positions,
      similarly to the KRAB domain itself. We propose that TIF1 beta is a mediator of
      the transcriptional repression exerted by the KRAB domain.

PMID- 9016655
TI  - Probing the role of the ATP-operated clamp in the strand-passage reaction of DNA
      gyrase.
AB  - The high-resolution structure of the 43 kDa N-terminal fragment of the DNA gyrase
      B protein shows a large cavity within the protein dimer. The approximate size of
      this cavity is 20 A, suggesting it could accommodate a DNA helix. Computer
      modelling studies of this cavity suggest that it contains a constriction,
      reducing the width to approximately 13 A, principally caused by the side chain of
      Arg286. We have used site-directed mutagenesis to alter this residue to Gln.
      Gyrase bearing this mutation shows virtually no supercoiling activity and near
      normal relaxation and DNA cleavage activities. The mutated protein has ATPase
      activity which cannot be stimulated by DNA. These data support the proposed role
      of the 43 kDa domain as an ATP-operated clamp which binds DNA during the
      supercoiling cycle. The lack of DNA-dependent ATPase of the mutant may indicate
      that binding of DNA within the clamp is a prerequisite for stimulation of the
      ATPase activity.

PMID- 9016656
TI  - Class III POU genes of zebrafish are predominantly expressed in the central
      nervous system.
AB  - POU genes encode a family of transcription factors involved in a wide variety of
      cell fate decisions and in the regulation of differentiation pathways. We have
      searched for POU genes in the zebrafish, a popular model organism for the study
      of early development of vertebrates. Besides five putative pseudogenes we have
      identified five POU genes that are expressed during embryogenesis. Probes
      obtained by PCR were used to isolate full-length cDNAs. Four of the isolated
      genes encode proteins with class III POU domains. Analysis of genomic clones
      suggests that the fish genes in general do not contain introns, similar to class
      III genes of mammals. However, the C-termini of two of the encoded proteins vary
      due to facultative splicing of a short intervening sequence. These two genes show
      very strong similarities in their sequence. They have probably arisen by gene
      duplication, possibly as part of a larger scale duplication of part of the
      zebrafish genome. Analysis of the expression of the class III genes shows that
      they are predominantly expressed in the central nervous system and that they may
      play important roles in patterning the embryonic brain.

PMID- 9016657
TI  - T7 RNA polymerase cannot transcribe through a highly knotted DNA template.
AB  - The ability of T7 RNA polymerase to transcribe a plasmid DNA in vitro in its
      linear, supercoiled, relaxed and knotted forms was analysed. Similar levels of
      transcription were found on each template with the exception of plasmids showing
      varying degrees of knotting (obtained using stoichiometric amounts of yeast
      topoisomerase II). A purified fraction of knotted DNA with a high number of nodes
      (crosses) was found to be refractory to transcription. The unknotting of the
      knotted plasmids, using catalytic amounts of topoisomerase II, restored their
      capacity as templates for transcription to levels similar to those obtained for
      the other topological forms. These results demonstrate that highly knotted DNA is
      the only topological form of DNA that is not a template for transcription. We
      suggest that the regulation of transcription, which depends on the topological
      state of the template, might be related to the presence of knotted DNA with
      different number of nodes.

PMID- 9016658
TI  - Two different RNA binding activities for the AU-rich element and the poly(A)
      sequence of the mouse neuronal protein mHuC.
AB  - HuC is one of the RNA binding proteins which are suggested to play important
      roles in neuronal differentiation and maintenance. We cloned and sequenced cDNAs
      encoding a mouse protein which is homologous to human HuC (hHuC). The longest
      cDNA encodes a 367 amino acid protein with three RNA recognition motifs (RRMs)
      and displays 96% identity to hHuC. Northern blot analysis showed that two
      different mRNAs, of 5.3 and 4.3 kb, for mouse HuC (mHuC) are expressed
      specifically in brain tissue. Comparison of cDNA sequences with the corresponding
      genomic sequence revealed that alternative 3' splice site selection generates two
      closely related mHuC isoforms. Iterative in vitro RNA selection and binding
      analyses showed that both HuC isoforms can bind with almost identical specificity
      to sequences similar to the AU-rich element (ARE), which is involved in the
      regulation of mRNA stability. Functional domain mapping using mHuC deletion
      mutants showed that the first RRM binds to ARE, that the second RRM has no RNA
      binding activity by itself, but facilitates ARE binding by the first RRM and that
      the third RRM has specific binding activity for the poly(A) sequence.

PMID- 9016659
TI  - Variegated expression of a globin transgene correlates with chromatin
      accessibility but not methylation status.
AB  - There are now many mammalian examples in which single cell assays of transgene
      activity have revealed variegated patterns of expression. We have previously
      reported that transgenes in which globin regulatory elements drive the lacZ
      reporter gene exhibit variegated expression patterns in mouse erythrocytes, with
      transgene activity detectable in only a sub-population of circulating erythroid
      cells. In order to elucidate the molecular mechanism responsible for variegated
      expression in this system, we have compared the chromatin structure and
      methylation status of the transgene locus in expressing and non-expressing
      populations of erythrocytes. We find that there is a difference in the chromatin
      conformation of the transgene locus between the two states. Relative to active
      transgenes, transgene loci which have been silenced exhibit a reduced sensitivity
      to general digestion by DNase I, as well as a failure to establish a transgene
      specific DNase I hypersensitive site, suggesting that silenced transgenes are
      situated within less accessible chromatin structures. Surprisingly, the
      restrictive chromatin structure observed at silenced transgene loci did not
      correlate with increased methylation, with transgenes from both active and
      inactive loci appearing largely unmethylated following analysis with methylation
      sensitive restriction enzymes and by sequencing PCR products derived from
      bisulphite-converted genomic DNA.

PMID- 9016660
TI  - Protonatable hairpins are conserved in the 5'-untranslated region of tymovirus
      RNAs.
AB  - The secondary structures of the 5'-untranslated region (5'-UTR) of five different
      tymoviruses have been determined by structure probing, computer prediction and
      sequence comparison. Despite large sequence differences, there are remarkable
      similarities in the secondary structure. In all viruses two or four hairpins are
      found, most of which contain a symmetrical internal loop consisting of adjacent C
      C or C-A mismatches. Since it is known that such mismatches can be protonated and
      protonated cytosines play an important role in RNA-protein interactions in
      tymoviral virions, the influence of pH on the conformation of the internal loop
      was studied. UV melting experiments and 1-dimensional proton NMR at varying pH
      values and salt concentrations confirm that the hairpins can be protonated under
      relatively mild conditions. The hairpin found in the 5'-UTR of erysimum latent
      virus, which has an asymmetrical internal loop consisting of cytosines and
      uridines, shows comparable behaviour. It is concluded that all tymoviral RNAs
      contain protonatable hairpins in the 5'-UTR. Binding experiments with empty viral
      capsids, however, do not yet establish a role in capsid protein binding.

PMID- 9016661
TI  - Functional Escherichia coli 23S rRNAs containing processed and unprocessed
      intervening sequences from Salmonella typhimurium.
AB  - We have introduced the intervening sequence (IVS) from 23S rRNA of the rrnD
      operon of Salmonella typhimurium into the equivalent position of Escherichia coli
      23S rRNA. Salmonella typhimurium 23S rRNA is fragmented due to the RNase III
      dependent removal of the approximately 100 nt stem-loop structure that comprises
      the IVS. In this study, we have found that insertion of the S. typhimurium IVS
      into E. coli 23S rRNA causes fragmentation of the RNA but does not affect
      ribosome function. Cells expressing the fragmented 23S rRNA exhibited wild-type
      growth rates. Fragmented RNA was found in the actively translating polysome pool
      and did not alter the sedimentation profile of ribosomal subunits, 70S ribosomes
      or polysomes. Finally, hybrid 23S rRNA carrying the A2058G mutation conferred
      high level erythromycin resistance indistinguishable from that of intact 23S rRNA
      carrying this mutation. These observations indicate that the presence of this IVS
      and its removal are phenotypically silent. As observed in an RNase III-deficient
      strain, processing of the IVS was not required for the production of functional
      ribosomes.

PMID- 9016662
TI  - In vivo persistence of DNA triple helices containing psoralen-conjugated
      oligodeoxyribonucleotides.
AB  - Triple helices represent an attractive method for modulating specific gene
      expression. In particular, cross-linking between a triplex-forming
      oligonucleotide (TFO) and its duplex DNA target, typically through the formation
      of psoralen photoadducts, allows efficient blocking of elongation by RNA
      polymerases in vitro. However, in vivo, this approach is limited by DNA repair of
      the photoadduct. Here we describe the use of an oligodeoxyribonucleotide 19mer
      psoralen-modified TFO to form covalent linkages between an oligonucleotide and
      both strands of the targeted duplex DNA, thereby efficiently blocking expression
      of a luciferase reporter gene. Most importantly, we demonstrate that both the
      psoralen cross-link and the purine-motif triplex remained intact for at least 72
      h post-transfection, indicating that such species can persist for an extended
      period of time in vivo. These findings support the feasibility of an antigene
      approach for the therapeutic regulation of specific gene expression.

PMID- 9016663
TI  - Interaction of the RecA protein of Escherichia coli with single-stranded
      oligodeoxyribonucleotides.
AB  - The RecA protein of Escherichia coli performs a number of ATP-dependent, in vitro
      reactions and is a DNA-dependent ATPase. Small oligodeoxyribonucleotides were
      used as DNA cofactors in a kinetic analysis of the ATPase reaction. Polymers of
      deoxythymidilic acid as well as oligonucleotides of mixed base composition
      stimulated the RecA ATPase activity in a length-dependent fashion. Both the
      initial rate and the extent of the reaction were affected by chain length. Full
      activity was seen with chain lengths > or = 30 nt. Partial activity was seen with
      chain lengths of 15-30 nt. The lower activity of shorter oligonucleotides was not
      simply due to a reduced affinity for DNA, since effects of chain length on KmATP
      and the Hill coefficient for ATP hydrolysis were also observed. The results also
      suggested that single-stranded DNA secondary structure frequently affects the
      ATPase activity of RecA protein with oligodeoxyribonucleotides.

PMID- 9016664
TI  - Isoguanine quartets formed by d(T4isoG4T4): tetraplex identification and
      stability.
AB  - The self-aggregation of the oligonucleotide d(T4isoG4T4) (1) is investigated.
      Based on ion exchange HPLC experiments and CD spectroscopy, a tetrameric
      structure is identified. This structure was formed in the presence of sodium ions
      and shows almost the same chromatographic mobility on ion exchange HPLC as
      d(T4G4T4) (2). The ratio of aggregate versus monomer is temperature dependent and
      the tetraplex of [d(T4isoG4T4)]4 is more stable than that of [d(T4G4T4)]4. A
      mixture of d(T4isoG4T4) and d(T4G4T4) forms mixed tetraplexes containing strands
      of d(T4isoG4T4) and d(T4G4T4).

PMID- 9016665
TI  - The joining of non-complementary DNA double-strand breaks by mammalian extracts.
AB  - We have developed a high efficiency system in which mammalian extracts join DNA
      double-strand breaks with non-complementary termini. This system has been used to
      obtain a large number of junction sequences from a range of different break-end
      combinations, allowing the elucidation of the joining mechanisms. Using an
      extract of calf thymus it was found that the major mechanism of joining was by
      blunt-end ligation following removal or fill-in of the single-stranded bases.
      However, some break-end combinations were joined through an efficient mechanism
      using short repeat sequences and we have succeeded in separating this mechanism
      from blunt-end joining by the biochemical fractionation of extracts.
      Characterization of activities and sequence data in an extensively purified
      fraction that will join ends by the repeat mechanism led to a model where joining
      is initiated by 3' strand invasion followed by pairing to short repeat sequences
      close to the break site. Thus the joining of double-strand breaks by mammalian
      extracts is achieved by several mechanisms and this system will allow the
      purification of the factors involved in each by the judicial choice of the non
      complementary ends used in the assay.

PMID- 9016666
TI  - Functional domains of transcription factor hGABP beta1/E4TF1-53 required for
      nuclear localization and transcription activation.
AB  - Transcription factor E4TF1 is the human homolog of GABP and has been renamed
      hGABP (human GABP). hGABP is composed of two types of subunits; hGABP beta1/E4TF1
      53 and the ets-related protein hGABP alpha/E4TF1-60. Both bind together to form
      an (alpha)2(beta1)2 heterotetrameric complex on DNA and activate transcription at
      specific promoters in vitro. Tetramer formation depends on two regions of hGABP
      beta1; the N-terminal region containing the Notch/ankyrin-type repeats is
      necessary for binding to hGABP alpha and the C-terminal region is necessary for
      homodimerization. In this report, we constructed various deletion mutants of
      hGABP beta1 in order to delimit the functional regions required for nuclear
      localization and transcription activity. We found that hGABP beta1 localization
      in the nucleus is dependent on a region located between amino acids 243 and 330
      and that the presence of hGABP beta1 influences the efficiency of hGABP alpha
      transport into the nucleus. Next, we demonstrated that the hGABP complex composed
      of alpha and beta1 subunits activates transcription from the adenovirus early 4
      promoter in vivo. This transcription activation needs the C-terminal region of
      hGABP beta1 and is consistent with results obtained with the in vitro assay.
      Furthermore, site-directed mutagenesis analysis of the C-terminal region reveals
      that the alpha-helix structure and the leucine residues are important for
      formation of a heterotetrameric complex with hGABP alpha in vitro and for
      transcription activation in vivo. These results suggest that hGABP beta1
      stimulates transcription as part of a heterotetrameric complex with hGABP alpha
      in vivo.

PMID- 9016667
TI  - Characterization of an RNP complex that assembles on the Rous sarcoma virus
      negative regulator of splicing element.
AB  - We have characterized an RNP complex that assembles in nuclear extracts on the
      negative regulator of splicing (NRS) element from Rous sarcoma virus. While no
      complex was detected by native gel electrophoresis under conditions that
      supported spliceosome assembly, gel filtration revealed a specific ATP
      independent complex that rapidly assembled on NRS RNA. No complexes were formed
      on non-specific RNA. Unlike the non-specific H complex, factors required for NRS
      complex assembly are limiting in nuclear extract. The NRS complex was not
      detected in reactions containing ATP and pre-formed complexes were dissociated in
      the presence of ATP. In addition, the assembly process was sensitive to high salt
      but NRS complexes were salt stable once formed. Assembly of the NRS complex
      appears functionally significant since mutated NRS RNAs that fail to inhibit
      splicing in vivo are defective for NRS complex assembly in nuclear extract. The
      probable relationship of the NRS complex to spliceosomal complexes is discussed.

PMID- 9016668
TI  - In vivo generation of 3' and 5' truncated species in the process of c-myc mRNA
      decay.
AB  - It has been demonstrated that the half-life of c-myc mRNA is modulated in
      response to physiological agents. The elucidation of the decay process and the
      identification of the critical steps in the in vivo c-myc mRNA degradation
      pathway can be approached by following the fate of c-myc mRNA under the influence
      of such factors. IFN-alpha was the factor used to modulate c-myc mRNA half-life
      in HeLa 1C5 cells, a stable clone derived from HeLa cells. This cell line carries
      multiple copies of the c-myc gene, under the control of the dexamethasone
      inducible mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Exposure of
      HeLa 1C5 cells to IFN-alpha resulted in a further 2-fold increase over the
      dexamethasone-induced c-myc mRNA. However, the c-myc mRNA in IFN-alpha treated
      cells was less stable than that in the control cells. RNase H mapping of the 3'
      untranslated region of c-myc mRNA revealed, in addition to the full length mRNA,
      three smaller fragments. These fragments were proven to be truncated, non
      adenylated c-myc mRNA species generated in vivo. Exposure of HeLa 1C5 cells to
      Interferon-alpha before induction with dexamethasone resulted in the enhanced
      presence of these intermediates. RNase H analysis of c-myc mRNA after actinomycin
      D chase revealed that deadenylation led to the formation of a relatively more
      stable oligoadenylated c-myc mRNA population which did not appear to be precursor
      to the truncated intermediates. The detection of truncated 3' end c-myc mRNA
      adenylated fragments as well, implies that the c-myc mRNA degradation process may
      follow an alternative pathway possibly involving endonucleolytic cleavage.

PMID- 9016669
TI  - Structure and function of the zeta-globin upstream regulatory element.
AB  - The human zeta-globin promoter contains a strong positive regulatory element in
      the 5' flanking region, designated the zeta-globin upstream regulatory element
      (URE). In this study, we define the minimal sequences required for URE function
      and characterize the associated protein-DNA interactions. Deletion experiments
      show that the URE spans a 60 bp region located between 220 and 279 bp 5' to the
      transcription start site. Further subdivision of this region shows that multiple
      cis acting sequences are present. Electrophoretic mobility shift assays
      demonstrate that the erythroid transcription factor GATA-1 binds a site at -230,
      and Sp1 and an unidentified factor bind a CCACC site at -240. The unidentified
      CCACC factor is distinct from two other CCACC factors, EKLF and BKLF/TEF-2. A
      third complex contains a novel DNA-binding activity that interacts with a site in
      the -269 to -255 region, designated URE binding factor (URE-BF). This factor is
      present in K562 cells that express zeta-globin, but is absent in the OCIM1 cell
      line, a human erythroid cell line that does not express zeta-globin. URE-BF
      appears to interact with a GATA factor, since formation of the URE-BF complex can
      be prevented by the presence of unlabeled oligonucleotides containing GATA sites.
      Finally, increasing the distance from the -230 GATA site to the two upstream
      sites causes a progressive decrease in zeta-globin promoter activity. There is no
      indication of a requirement for GATA-1 to be on the same side of the DNA helix as
      the other upstream factors. These results show that zeta-globin promoter function
      is highly dependent on a 60 bp region to which at least three different factors
      bind. Two of these factors may represent DNA-binding proteins not previously
      identified as important for regulation of globin gene expression. It is likely
      that these factors interact physically to create a functional regulatory unit.

PMID- 9016671
TI  - Fluorescence detection of specific sequence of nucleic acids by oxazole yellow
      linked oligonucleotides. Homogeneous quantitative monitoring of in vitro
      transcription.
AB  - We have developed a fluorescent DNA probe, oxazole yellow (YO)-linked
      oligonucleotide complementary to a target DNA/RNA, which can enhance the
      fluorescence on hybridizing with a target nucleotide. We demonstrated the
      applicability of the YO-linked oligonucleotide probe to real-time monitoring of
      the in vitro transcription process of a plasmid DNA constructed containing the 5'
      terminus non-coded region of hepatitis C virus RNA. In the process of in vitro
      transcription in the presence of YO-linked complementary oligonucleotide, the
      fluorescence of the reaction mixture showed a time-dependent linear increase
      corresponding to the generated target RNA product.

PMID- 9016670
TI  - RNA editing in the acceptor stem of squid mitochondrial tRNA(Tyr).
AB  - In squid (Loligo bleekeri) mitochondria, the two 3'-terminal nucleotides (G72
      G73) of the tRNA(Tyr) gene overlap with the two 5'-terminal nucleotides (G1-G2)
      of the downstream tRNA(Cys) gene. To elucidate the processing mechanism(s) of the
      tRNA molecules derived from this region, tRNAs were analyzed by sequencing cDNAs
      synthesized from circularized tRNAs. Nucleotides G1-G2 in tRNA(Cys) appeared to
      be without post-transcriptional conversion, whereas CCA was post
      transcriptionally added to the 3'-terminus. In contrast, in the majority of
      tRNAs(Tyr), G72-G73 were found to be converted to A72-A73, accompanied by the CCA
      addition. These results indicate that a precursor of tRNA(Tyr) is processed at
      U71 and two adenosines are attached prior to the CCA addition. Thus, we suggest
      that 5' processing of the precursor tRNA dominates 3' processing and maturation
      of the tRNA is mediated by a polyadenylylation enzyme in the mitochondria, a
      scenario which is consistent with the editing process proposed in land snail
      mitochondria. We also obtained intermediates, such as a premature tRNA lacking
      CCA that terminated at U71 and one with a single adenosine attached at position
      72, which support the suggested maturation process. However, although we failed
      to detect a tRNA(Cys) lacking G1-G2 at the 5'-terminus, we obtained cDNAs for
      tRNA(Tyr) with G72-G73 and the CCA terminus. This inconsistent result suggests
      the co-existence of another process(es) in the maturation of these tRNA molecules
      in squid mitochondria.

PMID- 9016672
TI  - Detection of all single-base mismatches in solution by chemiluminescence.
AB  - A rapid in-solution method for the detection of all 12 single-base mismatches is
      described. The technique is based on the hybridization protection assay (HPA)
      format that utilizes oligonucleotide probes labeled with a highly
      chemiluminescent acridinium ester (AE). Hydrolysis by weak base renders AE
      permanently non-chemiluminescent. When an AE-labeled probe hybridizes to an
      exactly complementary target, AE is protected from hydrolysis relative to the
      unhybridized conformation. Single-base mutations in the duplex adjacent to the
      site of AE attachment disrupt this protection resulting in rapid AE hydrolysis
      and loss of chemiluminescence. The discrimination effect was seen in both DNA and
      RNA. Studies of Tm values revealed that this effect is not due to a decrease in
      the overall stability of the duplex, suggesting the AE is responding to local
      structural changes in the double helix induced by mismatches. Using this
      principle all 12 single mismatches were clearly discriminated from the
      corresponding matched sequences. The assay is homogeneous, simple, sensitive,
      applicable to both amplified and non-amplified targets, and is completed in 30-60
      min. An example showing discrimination between wild-type and mutant sequences
      corresponding to the reverse transcriptase coding region of HIV-1 is given.

PMID- 9016673
TI  - Duplex-tetraplex equilibrium between a hairpin and two interacting hairpins of
      d(A-G)10 at neutral pH.
AB  - d(A-G)10 forms two helical structures at neutrality, at low ionic strength a
      single-hairpin duplex, and at higher ionic strength a double-hairpin tetraplex.
      An ionic strength-dependent equilibrium between these forms is indicated by
      native PAGE, which also reveals additional single-stranded species below 0.3 M
      Na+, probably corresponding to partially denatured states. The equilibrium also
      depends upon oligomer concentration: at very low concentrations, d(A-G)10
      migrates faster than the random coil d(C-T)10, probably because it is a more
      compact single hairpin; at high concentrations, it co-migrates with the linear
      duplex d(A-G)10 x d(C-T)10, probably because it is a two-hairpin tetraplex.
      Molecular weights measured by equilibrium sedimentation in 0.1 M Na+, pH 7,
      reveal a mixture of monomer and dimer species at 1 degree C, but only a monomer
      at 40 degrees C; in 0.6 M Na+, pH 7, only a dimer species is observed at 4
      degrees C. That the single- and double-stranded species are hairpin helices, is
      indicated by preferential S1 nuclease cleavage at the center of the oligomer(s),
      i.e., the loop of the hairpin(s). The UV melting transition below 0.3 M Na+ or
      K+, exhibits a dTm/dlog[Na+/K+] of 33 or 36 degrees C, respectively, consistent
      with conversion of a two-hairpin tetraplex to a single-hairpin duplex with
      extrahelical residues. When [Na+/K+] > or = 0.3 M, dTm/dlog [Na+/K+] is 19 or 17
      degrees C, respectively, consistent with conversion of a two-hairpin tetraplex
      directly to single strands. A two-hairpin structure stabilized by G-tetrads is
      indicated by differential scanning calorimetry in 0.15 M Na+/5 mM Mg2+, with
      deltaH of formation per mole of the two-hairpin tetraplex of -116.9 kcal or -29.2
      kcal/mol of G-tetrad.

PMID- 9016674
TI  - A UV resonance Raman study of hairpin dimer helices of d(A-G)10 at neutral pH
      containing intercalated dA residues and alternating dG tetrads.
AB  - The structure of the oligonucleotide d(A-G)10 in 0.6 M Na+, pH 7.0 has been
      investigated with UV resonance Raman (UVRR) spectroscopy. Variable wavelength
      excitation was used to distinguish the spectral contributions of dG and dA
      residues. Both classes of residues show UVRR hyperchromism with increasing
      temperature, reflecting unstacking of the bases. The dG residues melt relatively
      cooperatively with a Tm of approximately 42 degrees C. Unstacking is non
      cooperative for the dA residues, increasing linearly between 4 and 80 degrees C.
      G-tetrads at low temperature are indicated by UVRR frequency shifts of modes
      associated with C6=O and C2-NH2 of the dG residues, and of vibrations involving
      N7, all sites of H-bonding. However, there are no indications of interbase H
      bonds for the dA residues, showing they do not form H-bonded tetrads. Most of the
      bases are oriented anti about the glycosyl bond, but at 4 degrees C a fraction of
      the residues are syn. These results, together with the findings by Shiber et al.
      [Shiber,M.C., Braswell,E.H., Klump,H. and Fresco,J.R. (1996) Nucleic Acids Res.
      24, 5004-5012] that d(A-G)10 under comparable conditions has the molecular weight
      of a dimer, support a model in which two hairpins interact to form a helical
      structure with G-tetrads and intercalated dA residues.

PMID- 9016675
TI  - Selective amplification of RNA utilizing the nucleotide analog dITP and Thermus
      thermophilus DNA polymerase.
AB  - The ability to selectively amplify RNA in the presence of genomic DNA of
      analogous sequence is cumbersome and requires implementation of critical controls
      for genes lacking introns. The convenient approaches of either designing
      oligonucleotide primers at the splice junction or differentiating the target
      sequence based on the size difference obtained by the presence of the intron are
      not possible. Our strategy for the selective amplification of RNA targets is
      based on the enzymology of a single thermostable DNA polymerase and the ability
      to modulate the strand separation temperature requirements for PCR amplification.
      Following reverse transcription of the RNA by recombinant Thermus thermophilus
      DNA polymerase (rTth pol), the resulting RNAxDNA hybrid is digested by the RNase
      H activity of rTth pol, allowing the PCR primer to hybridize and initiate second
      strand cDNA synthesis. Substitution of one or more conventional nucleotides with
      nucleotide analogs that decrease base stacking interactions and/or hydrogen
      bonding (e.g. hydroxymethyldUTP or dITP) during the first- and second-strand cDNA
      synthesis step reduces the strand separation temperature of the resultant DNAxDNA
      duplex. Alteration of the thermal cycling parameters of the subsequent PCR
      amplification, such that the strand separation temperature is below that required
      for denaturation of genomic duplex DNA composed of standard nucleotides, prevents
      the genomic DNA from being denatured and therefore amplified.

PMID- 9016676
TI  - Effect of highly fragmented DNA on PCR.
AB  - We characterized the behavior of polymerase chain reactions (PCR) using degraded
      DNA as a template. We first demonstrated that fragments larger than the initial
      template fragments can be amplified if overlapping fragments are allowed to
      anneal and extend prior to routine PCR. Amplification products increase when
      degraded genomic DNA is pretreated by polymerization in the absence of specific
      primers. Secondly, we measured nucleotide uptake as a function of template DNA
      degradation. dNTP incorporation initially increases with increasing DNA
      fragmentation and then declines when the DNA becomes highly degraded. We
      demonstrated that dNTP uptake continues for >10 polymerization cycles and is
      affected by the quality and quantity of template DNA and by the amount of
      substrate dNTP. These results suggest that although reconstruction of degraded
      DNA may allow amplification of large fragments, reconstructive polymerization and
      amplification polymerization may compete. This was confirmed in PCR where the
      addition of degraded DNA reduced the resultant product. Because terminal
      deoxynucleotidyl transferase activity of Taq polymerase may inhibit 3' annealing
      and restrict the length of template reconstruction, we suggest modified PCR
      techniques which separate reconstructive and amplification polymerization
      reactions.

PMID- 9016678
TI  - High-throughput plasmid mini preparations facilitated by micro-mixing.
AB  - We have developed a reliable high-throughput plasmid isolation system using a 96
      well plate format. This system combines a novel glass bead micro-mixing method
      with modified alkaline lysis and Sephacryl S-500 DNA purification procedures.
      Mechanical forces generated by vortexing glass beads inside each well of the 96
      well plates ensure that the bacterial pellets are homogeneously resuspended, the
      cells are completely lyzed, and the resulting bacterial lysates are thoroughly
      mixed with the potassium acetate solution. The vortexing speed and duration for
      glass bead mixing have been standardized to facilitate plasmid DNA yields without
      significant adjustments.

PMID- 9016677
TI  - An enhancer LEF-1/TCF-1 site is essential for insertion site-independent
      transgene expression in thymus.
AB  - Transcriptional activation of eukaryotic genes involves assembly of specific
      multiprotein complexes on the promoters and enhancers of the genes. Recently, it
      has been proposed that the role of some of the proteins in the complex may be
      architectural, involving DNA bending, orchestration of protein-protein
      interaction and modulation of nucleosome structure. This role has been proposed
      for the HMG proteins LEF-1 and TCF-1. We examined the role of a LEF-1/TCF-1
      binding site in the human adenosine deaminase (ADA) thymic enhancer. Mutational
      analysis demonstrated that a functional LEF-1/TCF-1 binding site is not required
      for enhancer-mediated transcriptional activation in transient transfection
      studies, but is essential for enhancer function in the in vivo chromatin context
      of transgenic mice. Mutation of the LEF-1/TCF-1 site destroyed the ability of the
      ADA enhancer/locus control region to specify high level, insertion site
      independent transgene expression in thymus. DNase I and DpnII accessibility
      experiments indicated dramatic changes in the chromatin organization of the ADA
      enhancer in transgenic mice with a mutated LEF-1/TCF-1 site. This supports the
      hypothesis that factors binding the LEF-1/TCF-1 site play an architectural role
      during the in vivo activation of the ADA enhancer, possibly involving chromatin
      modification.

PMID- 9016679
TI  - A novel system for the rapid generation of precise DNA deletions.
AB  - To generate DNA deletions, a tandem array of class IIS restriction enzyme
      recognition sites was cloned into a plasmid. The recognition sites were arranged
      so that each enzyme cleaves at a different site within an adjacent target
      sequence. Digestion with both enzymes followed by end repair and ligation
      resulted in the deletion of DNA between the two sites of cleavage. Because both
      recognition sites are preserved following deletion, it was found that sequential
      deletions could be generated using cycles of restriction enzyme digestion, end
      repair and ligation. Therefore, this system represents a valuable tool in the
      definition of functional DNA sequences.

PMID- 9016680
TI  - Inhibition of self-splicing group I intron RNA: high-throughput screening assays.
AB  - High-throughput screening assays have been developed to rapidly identify small
      molecule inhibitors targeting catalytic group I introns. Biochemical reactions
      catalyzed by a self-splicing group I intron derived from Pneumocystis carinii or
      from bacteriophage T4 have been investigated. In vitro biochemical assays
      amenable to high-throughput screening have been established. Small molecules that
      inhibit the functions of group I introns have been identified. These inhibitors
      should be useful in better understanding ribozyme catalysis or in therapeutic
      intervention of group I intron-containing microorganisms.

PMID- 9016681
TI  - A method for high efficiency YAC lipofection into murine embryonic stem cells.
AB  - We describe a modified protocol for introducing yeast artificial chromosomes
      (YACs) into murine embryonic stem (ES) cells by lipofection. With a decreased
      DNA:cell ratio, increased concentration of condensing agents and altered culture
      conditions, this protocol reduces the requirement for YAC DNA to a few
      micrograms, improves the recovery of neomycin-resistant ES colonies and increases
      the yield of clones containing both flanking vector markers and insert. These
      modifications enable generation of sufficient 'intact' transgenic clones for
      biological analysis with a single experiment.

PMID- 9016683
TI  - Rapid analysis of DNA methylation using new restriction enzyme sites created by
      bisulfite modification.
AB  - Bisulfite converts non-methylated cytosine in DNA to uracil leaving 5
      methylcytosine unaltered. Here, predicted changes in restriction enzyme sites
      following reaction of genomic DNA with bisulfite and amplification of the product
      by the polymerase chain reaction (PCR) were used to assess the methylation of CpG
      sites. This procedure differs from conventional DNA methylation analysis by
      methylation-sensitive restriction enzymes because it does not rely on an absence
      of cleavage to detect methylated sites, the two strands of DNA produce different
      restriction enzyme sites and may be differentially analyzed, and closely related
      sequences may be separately analyzed by using specific PCR primers.

PMID- 9016682
TI  - Nucleic acid scanning-by-hybridization of enterohemorrhagic Escherichia coli
      isolates using oligodeoxynucleotide arrays.
AB  - Nucleic acid scanning by hybridization (NASBH) is a non-electrophoretic typing
      strategy that uses gridded oligonucleotides to reproducibly characterize
      arbitrarily amplified nucleic acid sequences. Membrane-bound arrays of terminally
      degenerate oligonucleotides were hybridized to DNA amplification fingerprinting
      (DAF) products from enterohemorrhagic Escherichia coli O157:H7 isolates.
      Numerical and cluster analysis of 64 isolates, selected by DAF to represent a
      single dominant amplification type identified 14 hybridization types. Results
      show that NASBH is a powerful alternative for the identification of closely
      related bacteria, can be used successfully in epidemiological studies, and holds
      potential in general nucleic acid diagnostics.

PMID- 9016684
TI  - 3' cycle-labeled oligonucleotides with predictable length for primer extension
      and transgene analysis.
AB  - Efficient labeling of short oligos at their 3'-ends was achieved through
      polymerase chain reaction. The length of cycled-labeled oligos can be accurately
      predicted by omitting one or more dNTPs in the labeling step. Thus, labeled
      oligos can be simply column-purified, eliminating the need for tedious gel
      purification. We demonstrated the effectiveness of this technique in determining
      the transcription start site of a given gene and in transgene analysis to
      differentiate the transcript of an endogenous gene from that of an introduced
      homologous gene. This technique could be widely extended to other molecular
      biology applications in which labeled oligos are employed.

PMID- 9016685
TI  - Cytosine-specific chemical probing of DNA using bromide and monoperoxysulfate.
AB  - Bromination of cytosine and formation of a piperidine-labile site are observed
      when two simple salts, KBr and KHSO5, are allowed to react with single-stranded
      oligodeoxynucleotides. Selectivity for C compared with T, G or A is typically a
      factor of 4 or more; selectivity for Cs in a single-stranded region such as a C
      bulge is nearly a factor of 10 compared with duplex Cs. Low reactivity and little
      base selectivity are observed using duplex DNA, although increased concentrations
      of reagents lead to complete degradation of the DNA. The results suggest that
      these conditions for in situ generation of Br2 constitute a useful tool for
      examination of the exposure of a non-duplex cytosine base in folded DNA
      structures.

PMID- 9016686
TI  - A modified and improved method for bisulphite based cytosine methylation
      analysis.
AB  - Sequencing of bisulphite modified genomic DNA is the most powerful method to
      determine methylation patterns in chromosomal DNA. In many experimental systems,
      the amount of material available for analysis is very small which makes it
      necessary to perform experiments at extreme levels of sensitivity and
      reproducibility. In this communication, we present an improved modification of
      the bisulphite based sequencing method. Our strategy is to perform the bisulphite
      treatment and subsequent PCR steps on material embedded into agarose beads. This
      prevents loss of DNA during the experimental procedure and ensures an optimal
      bisulphite reactivity by maintaining the DNA in the single stranded form. The
      modification improves previously published protocols in that it facilitates the
      handling of probes and reproducibly reaches a very high level of sensitivity.

PMID- 9016702
TI  - Differences in perceived shape from shading correlate with activity in early
      visual areas.
AB  - The perception of shape from shading depends on the orientation of the shading
      gradient [1] [2] [3] [4]. Displays composed of elements with vertically oriented
      shading gradients of opposite polarity produce a strong and stable percept of
      'concave' and 'convex' elements. If the shading gradients are rotated 90 degrees
      , the depth percept is reduced and appears much more ambiguous. Results from
      psychophysical [1] [2] [3] [4] [5] [6], neuropsychological [7] and computational
      studies [8] [9] suggest that the perception of shape from shading engages
      specific mechanisms in early cortical visual areas. In a three-dimensional
      functional magnetic resonance imaging (fMRI) study at 1.5 Tesla using a three
      dimensional, interleaved-echoplanar imaging technique and a surface radio
      frequency (RF) coil placed under the visual cortex, we investigated the activity
      in these early visual areas associated with viewing shape from shading displays
      at two different orientations. We found significantly greater activation in area
      V1 and neighbouring low-level visual areas of cortex when subjects viewed
      displays that led to weak and unstable depth percepts than when they viewed
      displays that led to strong and stable depth percepts.

PMID- 9016703
TI  - Zp3-cre, a transgenic mouse line for the activation or inactivation of loxP
      flanked target genes specifically in the female germ line.
AB  - The site-specific DNA recombinase Cre is being used to develop a new generation
      of tools for controlling gene expression in mice [1]. Cre mediates the
      recombination of two directly repeated target (loxP) sites to a single loxP site,
      with concomitant excision of the DNA segment flanked by the loxP sites (the
      'floxed' DNA). Such recombination can function to activate a gene by excising a
      floxed DNA segment that blocks expression because it either separates the
      regulatory and coding sequences of the gene [2] or interrupts the gene's open
      reading frame. Conversely, DNA excision can inactivate a gene if an essential
      fragment of the gene is floxed [3]. Gene activation or inactivation in vivo can
      be achieved by mating two different animals, one carrying a 'target gene' with
      appropriately placed loxP sites and one carrying a cre transgene. In most cases,
      the specificity of the system is dependent upon stringent regulation of cre
      expression. We describe here a mouse line in which cre expression is controlled
      by regulatory sequences from the mouse zona pellucida 3 (Zp3) gene, which is
      normally expressed exclusively in the growing oocyte prior to the completion of
      the first meiotic division [4]. We show that in target-bearing Zp3-cre mice, Cre
      mediated recombination of the target gene apparently occurs in 100 % of oocytes.
      Moreover, Cre activity is not detected in the somatic tissues of most target
      bearing Zp3-cre mice. Potential uses for this mouse line are discussed.

PMID- 9016704
TI  - Oligodendrocyte precursor cells count time but not cell divisions before
      differentiation.
AB  - During vertebrate development, many types of precursor cell divide a limited
      number of times before they stop and terminally differentiate. It is unclear what
      limits cell proliferation and causes the cells to stop dividing when they do. The
      stopping mechanisms are important as they influence both the number of
      differentiated cells generated and the timing of differentiation. We have been
      studying the 'stopping' problem in the oligodendrocyte cell lineage [1] [2],
      which is responsible for myelination in the vertebrate central nervous system.
      Previous studies demonstrated that the proliferation of oligodendrocyte precursor
      cells isolated from the developing rat optic nerve is limited by an intrinsic
      'clock' mechanism [3], which consists of two components: a counting mechanism
      that counts time or cell divisions, and an effector mechanism that arrests the
      cell cycle and initiates cell differentiation when the appropriate time is
      reached [4] [5]. In the present study, we address the question of whether the
      counting mechanism operates by counting cell divisions. We show that precursor
      cells cultured at 33 degrees C divide more slowly but stop dividing and
      differentiate sooner, after fewer cell divisions, than when they are cultured at
      37 degrees C, indicating that the counting mechanism does not count cell
      divisions but measures time in some other way. In addition, we show that the
      levels of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) rise faster at 33
      degrees C than at 37 degrees C, consistent with previous evidence [6] that the
      accumulation of p27 may be part of the counting mechanism.

PMID- 9016705
TI  - A LEAFY co-regulator encoded by UNUSUAL FLORAL ORGANS.
AB  - BACKGROUND: . Development of petals and stamens in Arabidopsis flowers requires
      the function of the organ-identity gene APETALA3 (AP3), whose RNA is expressed
      specifically in petal and stamen primordia. AP3 expression is positively
      regulated by the meristem-identity gene LEAFY (LFY), which is expressed
      ubiquitously in young flowers. It is unknown how the transition from ubiquitous
      expression of LFY to region-specific expression of AP3 is made. It has previously
      been proposed for Antirrhinum that another gene, FIMBRIATA (FIM), mediates
      between the LFY and AP3 orthologs, with the three genes acting in a simple
      regulatory hierarchy. FIM is activated later than the LFY ortholog, and its
      expression is more restricted than that of the LFY ortholog. RESULTS: . We have
      tested whether the model proposed for Antirrhinum applies to Arabidopsis, by
      creating transgenic plants in which the FIM ortholog UNUSUAL FLORAL ORGANS (UFO)
      was expressed constitutively from the promoter of the cauliflower mosaic virus
      35S gene. In 35S::UFO flowers, AP3 was expressed precociously and ectopically,
      confirming that UFO is an upstream regulator of AP3. However, 35S::UFO could not
      restore petal and stamen development in lfy mutants, indicating that UFO can only
      function in the presence of LFY activity. The failure of 35S::UFO to rescue lfy
      mutants is consistent with our observation that UFO expression levels are not
      markedly changed in lfy mutants. CONCLUSIONS: . We conclude that UFO is not a
      simple mediator between meristem- and organ-identity genes, but is likely to be a
      partially dispensable co-regulator that acts together with LFY. The interplay
      between LFY and UFO provides a paradigm for how a global regulator such as LFY
      activates selected target genes only in restricted regions within its expression
      domain.

PMID- 9016706
TI  - Proneural function of neurogenic genes in the developing Drosophila eye.
AB  - BACKGROUND: . Intercellular signals are major determinants of cell fate during
      development. Certain signals and receptors are important for many different cell
      fate decisions, suggesting that cellular responses to similar signals change
      during development. Few transitions between such distinct cellular responses have
      been studied. The Drosophila genes Notch and hedgehog function during
      intracellular signaling at various stages of development. In the specific case of
      development of the Drosophila eye, expression of the proneural gene atonal is
      induced in response to Hedgehog signaling and then becomes subject to
      autoregulation. The receptor protein Notch has previously been reported to
      function in the selection of single founder photoreceptor cells (R8 cells) by
      inhibiting atonal expression. On this basis, complete elimination of Notch gene
      function would be expected to cause neural hyperplasia in the eye. RESULTS: .
      Contrary to expectation, we detect a reduction in neural differentiation both in
      cells expressing a conditional Notch allele and in those lacking expression of
      either Notch or its ligand Delta. We show here that Notch signaling acts after
      the initial Hedgehog-driven expression of atonal to enhance proneural competence
      of the atonal-expressing cells and also to terminate their response to the
      Hedgehog signals. This occurs before the Notch-induced lateral inhibition of
      atonal expression within the same cells. CONCLUSION: . Notch has sequentially
      opposite effects on the same cells, by first promoting and then inhibiting
      proneural gene function. This apparently paradoxical sequence of events has two
      possible consequences. Firstly, coupling of alternative cellular responses to the
      same receptor may prevent them from occurring simultaneously. Secondly,
      consecutive regulatory processes become temporally coupled, so that these events
      follow on from each other, without gaps or overlaps.

PMID- 9016707
TI  - CD22 is a negative regulator of B-cell receptor signalling.
AB  - BACKGROUND: . Antibody responses are triggered by binding of antigen to the B
      cell antigen receptor (BCR). The strength of the resulting signal determines the
      outcome of the response, which may vary from the induction of tolerance to the
      antigen, to the production of specific high-affinity antibodies. Additional cell
      surface proteins assist the BCR in its function, and can facilitate or inhibit an
      antibody response. CD22 is a BCR-associated transmembrane protein, the
      cytoplasmic tail of which contains three immunoreceptor tyrosine-based inhibitory
      motifs. These motifs are phosphorylated upon BCR-crosslinking, and can bind the
      tyrosine phosphatase SHP-1, a putative negative regulator of signalling from the
      BCR. In order to assess the role of CD22 in vivo, we have generated CD22(-/-)
      mice by targeted gene inactivation. RESULTS: . In CD22(-/-) mice, B-cell
      development is normal. There are normal numbers of peripheral B cells, but these
      have a more mature phenotype. In addition, recirculating B cells are absent from
      the bone marrow. However, the distribution of the two B-cell subtypes, B-1 and B
      2, is normal. After BCR-crosslinking in vitro, splenic CD22(-/-) B cells show an
      increased Ca2+ influx and a lower survival due to an increased induction of
      apoptosis. In contrast, there is an increased proliferative response to the B
      cell mitogen lipopolysaccharide (LPS). A shorter average lifespan in the B-cell
      compartment is also found in vivo. Furthermore, T-cell independent immune
      responses are impaired, whereas T-cell dependent responses are normal.
      CONCLUSIONS: . The absence of CD22 expression lowers the signalling threshold for
      BCR-crosslinking and can thus influence the fate of the B cell. We propose that
      the low threshold leads to hyperresponsiveness of the B cells and a chronic basal
      activation. In this model, engagement of the receptor without T-cell help leads
      to an increased induction of apoptosis, thus explaining the shorter lifespan of
      CD22(-/-) B cells and the low response to T-cell independent antigens. The
      alteration in B-cell phenotype and the higher levels of LPS-reactivity are
      attributable to the chronic basal stimulation.

PMID- 9016708
TI  - Interactions between colour and motion in image segmentation.
AB  - BACKGROUND: . An important early stage in visual processing is image
      segmentation, in which similar regions are grouped together and segregated from
      dissimilar regions, so that distinct objects ultimately may be located and
      recognized. In the natural world, objects are simultaneously characterized by
      colour, motion, texture and other visual attributes. How does the human visual
      system combine these attributes to segment the image? Although colour and motion
      information are conveyed by distinct functional streams from retina to visual
      cortex, there is increasing evidence for early and substantial cross-talk between
      the streams. Here, we explore psychophysical evidence for interactions between
      colour and motion in image segmentation. RESULTS: . Observers performed forced
      choice segmentation tasks on random-dot stimuli. The dots in the vertical target
      figure were distinguished from the background dots by a different distribution of
      speeds or colours. To explore interactions between motion and colour
      segmentation, we added motion noise to the colour signal (or vice versa) by
      assigning all dots speeds (or colours) drawn from one of several noise
      distributions. Motion noise severely affects segmentation by colour. Motion noise
      defined by a broad distribution of speeds degrades colour segmentation, but a two
      speed motion distribution (half moving up, half moving down) facilitates colour
      segmentation. Control experiments prove that the facilitatory effect is not
      caused by integrating colour information over different frames, nor can it be
      explained by probability summation over the two planes of moving dots. Colour
      noise also affects motion segmentation, but under a more restricted range of
      conditions, and not in a facilitatory way. CONCLUSIONS: . Colour and motion
      information interact at early stages during image segmentation, before decisions
      based on either cue in isolation are made. The robust bipolar effects of motion
      information on segmentation by colour indicate that the establishment of motion
      defined surfaces takes primacy, and that such surfaces constitute important
      primitives for further processing.

PMID- 9016712
TI  - Crystal structure of common type acylphosphatase from bovine testis.
AB  - BACKGROUND: Acylphosphatase (ACP) is a low molecular weight phosphomonohydrolase
      catalyzing with high specificity the hydrolysis of the carboxyl-phosphate bond
      present in acylphosphates. The enzyme is thought to regulate metabolic processes
      in which acylphosphates are involved, such as glycolysis and the production of
      ribonucleotides. Furthermore the enzyme is capable of hydrolyzing the phospho
      aspartyl intermediate formed during the action of membrane pumps such as
      (Ca2++Mg2+) ATPase. Although the tertiary structure of a muscle ACP has been
      determined by NMR spectroscopy, little is known about the catalytic mechanism of
      ACP and further structures might provide an increased understanding. RESULTS: The
      structure of 'common type' ACP from bovine testis has been determined by X-ray
      crystallography to a resolution of 1.8 A. The structure has been refined to an R
      factor of 17.0 % using all data between 15 and 1.8 A. The binding of a sulphate
      and a chloride ion in the active centre allows a detailed description of this
      site. The overall protein folds of common type and muscle ACP are similar but
      their loops have very different conformations. These differences, in part, are
      probably caused by the binding of the ions in the active site of the common type
      form. The phosphate-binding loop of ACP shows some remarkable similarities to
      that of low molecular weight protein tyrosine phosphatase. CONCLUSIONS: The
      active site of ACP has been located, enabling a reaction mechanism to be
      suggested in which the phosphate moiety bound to Arg23 acts as a base,
      abstracting a proton from a nucleophilic water molecule liganded to Asn41. The
      transition-state intermediate is stabilized by the phosphate-binding loop. We
      suggest the catalysis to be substrate assisted, which probably explains why this
      enzyme can only hydrolyze acylphosphates.

PMID- 9016713
TI  - A tale of two terminators: crystal structures sharpen the debate on DNA
      replication fork arrest mechanisms.
AB  - The structure of the Tus-Ter DNA replication fork arrest complex of Escherichia
      coli reveals a novel architecture for the bound Tus protein and a new type of DNA
      binding motif. The structure of the complex may explain how Tus can block
      movement of a replication fork approaching from one direction and not the other.

PMID- 9016714
TI  - The novel acidophilic structure of the killer toxin from halotolerant yeast
      demonstrates remarkable folding similarity with a fungal killer toxin.
AB  - BACKGROUND: Several strains of yeasts and fungi produce proteinous substances,
      termed killer toxins, which kill sensitive strains. The SMK toxin, secreted by
      the halotolerant yeast Pichia farinosa KK1 strain, uniquely exhibits its maximum
      killer activity under conditions of acidic pH and high salt concentration. The
      toxin is composed of two distinct subunits, alpha and beta, which tightly
      interact with each other under acidic conditions. However, they are easily
      dissociated under neutral conditions and lose the killer activity. The three
      dimensional structure of the SMK toxin will provide a better understanding of the
      mechanism of toxicity of this protein and the cause of its unique pH-dependent
      stability. RESULTS: Two crystal structures of the SMK toxin have been determined
      at 1.8 A resolution in different ionic strength conditions. The two subunits,
      alpha and beta, are jointly folded into an ellipsoidal, single domain structure
      belonging to the alpha/beta-sandwich family. The folding topology of the SMK
      toxin is essentially the same as that of the fungal killer toxin, KP4. This
      shared topology contains two left-handed split betaalphabeta motifs, which are
      rare in the other proteins. Many acidic residues are clustered at the bottom of
      the SMK toxin molecule. Some of the carboxyl sidechains interact with each other
      through hydrogen bonds. The ionic strength difference induces no evident
      structural change of the SMK toxin except that, in the high ionic strength
      crystal, a number of sulfate ions are electrostatically bound near the basic
      residues which are also locally distributed at the bottom of the toxin molecule.
      CONCLUSIONS: The two killer toxins, SMK and KP4, share a unique folding topology
      which contains a rare structural motif. This observation may suggest that these
      toxins are evolutionally and/or functionally related. The pH-dependent stability
      of the SMK toxin is a result of the intensive interactions between the carboxyl
      groups. This finding is important for protein engineering, for instance, towards
      stabilization of the toxin molecule in a broader pH range. The present
      crystallographic study revealed that the structure of the SMK toxin itself is
      hardly affected by the ionic strength, implying that a high salt concentration
      affects the sensitivity of the cell against the toxin.

PMID- 9016715
TI  - The molecular basis for allergen cross-reactivity: crystal structure and IgE
      epitope mapping of birch pollen profilin.
AB  - BACKGROUND: The profilins are a group of ubiquitous actin monomer binding
      proteins that are responsible for regulating the normal distribution of
      filamentous actin networks in eukaryotic cells. Profilins also bind
      polyphosphoinositides, which can disrupt the profilin-action complex, and proline
      rich ligands which localize profilin to sites requiring extensive actin filament
      accumulation. Profilins represent cross-reactive allergens for almost 20 % of all
      pollen allergic patients. RESULTS: We report the X-ray crystal structure of birch
      pollen profilin (BPP) at 2.4  resolution. The major IgE-reactive epitopes have
      been mapped and were found to cluster on the N- and C-terminal alpha helices and
      a segment of the protein containing two strands of the beta sheet. The overall
      fold of this protein is similar to that of the mammalian and amoeba profilins,
      however, there is a significant change in the orientation of the N-terminal alpha
      helix in BPP. This change in orientation alters the topography of a hydrophobic
      patch on the surface of the molecule, which is thought to be involved in the
      binding of proline-rich ligands. CONCLUSIONS: Profilin has been identified as an
      important cross-reactive allergen for patients suffering from multivalent type I
      allergy. The prevalent epitopic areas are located in regions with conserved
      sequence and secondary structure and overlap the binding sites for natural
      profilin ligands, indicating that the native ligand-free profilin acts as the
      original cross-sensitizing agent. Structural homology indicates that the basic
      features of the G actin-profilin interaction are conserved in all eukaryotic
      organisms, but suggests that mechanistic differences in the binding of proline
      rich ligands may exist. The structure of BPP provides a molecular basis for
      understanding allergen cross-reactivity.

PMID- 9016716
TI  - Crystal structure of a thermostable Bacillus DNA polymerase I large fragment at
      2.1 A resolution.
AB  - BACKGROUND: The study of DNA polymerases in the Pol l family is central to the
      understanding of DNA replication and repair. DNA polymerases are used in many
      molecular biology techniques, including PCR, which require a thermostable
      polymerase. In order to learn about Pol I function and the basis of
      thermostability, we undertook structural studies of a new thermostable DNA
      polymerase. RESULTS: A DNA polymerase large, Klenow-like, fragment from a
      recently identified thermostable strain of Bacillus stearothermophilus (BF) was
      cloned, sequenced, overexpressed and characterized. Its crystal structure was
      determined to 2.1 A resolution by the method of multiple isomorphous replacement.
      CONCLUSIONS: This structure represents the highest resolution view of a Pol I
      enzyme obtained to date. Comparison of the three Pol I structures reveals no
      compelling evidence for many of the specific interactions that have been proposed
      to induce thermostability, but suggests that thermostability arises from
      innumerable small changes distributed throughout the protein structure. The
      polymerase domain is highly conserved in all three proteins. The N-terminal
      domains are highly divergent in sequence, but retain a common fold. When present,
      the 3'-5' proofreading exonuclease activity is associated with this domain. Its
      absence is associated with changes in catalytic residues that coordinate the
      divalent ions required for activity and in loops connecting homologous secondary
      structural elements. In BF, these changes result in a blockage of the DNA-binding
      cleft.

PMID- 9016717
TI  - The crystal structure of phenylalanyl-tRNA synthetase from thermus thermophilus
      complexed with cognate tRNAPhe.
AB  - BACKGROUND: In the translation of the genetic code each aminoacyl-tRNA synthetase
      (aaRS) must recognize its own (cognate) tRNA and attach the corresponding amino
      acid to the acceptor end of tRNA, discriminating all the others. The(alphabeta)2
      phenylalanyl-tRNA synthetase (PheRS) is one of the most complex enzymes in the
      aaRS family and is characterized by anomalous charging properties. Structurally,
      the enzyme belongs to class II aaRSs, as its catalytic domain is built around an
      antiparallel beta sheet, but functionally it resembles class I as it
      aminoacylates the 2'OH of the terminal ribose of tRNA (class II aaRSs
      aminoacylate the 3'OH). With the availability of the three-dimensional structure
      of the complex between multisubunit PheRS and tRNAPhe, a fuller picture of the
      specific tRNA-aaRS interactions is beginning to emerge. RESULTS: The crystal
      structure of Thermus thermophilus PheRS complexed with cognate tRNA has been
      solved at 3.28 A resolution. It reveals that one tRNAPhe molecule binds across
      all four PheRS subunits. The interactions of PheRS with tRNA stabilize the
      flexible N-terminal part of the alpha subunit, which appeared to form the
      enzyme's 11th domain, comprising a coiled-coil structure (helical arm) built up
      of two long antiparallel alpha helices. The helical arms are similar to those
      observed in SerRS and are in the same relative orientation with respect to the
      catalytic domain. Anticodon recognition upon tRNA binding is performed by the B8
      domain, the structure of which is similar to that of the RNA-binding domain (RBD)
      of the small spliceosomal protein U1A. The Th. thermophilus PheRS approaches the
      anticodon loop from the minor groove side. CONCLUSIONS: The mode of interactions
      with tRNA explains the absolute necessity for the (alphabeta)2 architecture of
      PheRS. The interactions of tRNAPhe with PheRS and particularly with the coiled
      coil domain of the alpha subunit result in conformational changes in TPsiC and D
      loops seen by comparison with uncomplexed yeast tRNAPhe. The tRNAPhe is a newly
      recognized type of RNA molecule specifically interacting with the RBD fold. In
      addition, a new type of anticodon-binding domain emerges in the aaRS family. The
      uniqueness of PheRS in charging 2'OH of tRNA is dictated by the size of its
      adenine-binding pocket and by the local conformation of the tRNA's CCA end.

PMID- 9016718
TI  - The DNA-binding domain of OmpR: crystal structures of a winged helix
      transcription factor.
AB  - BACKGROUND: The differential expression of the ompF and ompC genes is regulated
      by two proteins that belong to the two component family of signal transduction
      proteins: the histidine kinase, EnvZ, and the response regulator, OmpR. OmpR
      belongs to a subfamily of at least 50 response regulators with homologous C
      terminal DNA-binding domains of approximately 98 amino acids. Sequence homology
      with DNA-binding proteins of known structure cannot be detected, and the lack of
      structural information has prevented understanding of many of this familys
      functional properties. RESULTS: We have determined the crystal structure of the
      Escherichia coli OmpR C-terminal domain at 1.95 A resolution. The structure
      consists of three alpha helices packed against two antiparallel beta sheets. Two
      helices, alpha2 and alpha3, and the ten residue loop connecting them constitute a
      variation of the helix-turn-helix (HTH) motif. Helix alpha3 and the loop
      connecting the two C-terminal beta strands, beta6 and beta7, are probable DNA
      recognition sites. Previous mutagenesis studies indicate that the large loop
      connecting helices alpha2 and alpha3 is the site of interaction with the alpha
      subunit of RNA polymerase. CONCLUSIONS: OmpRc belongs to the family of 'winged
      helix-turn-helix' DNA-binding proteins. This relationship, and the results from
      numerous published mutagenesis studies, have helped us to interpret the functions
      of most of the structural elements present in this protein domain. The structure
      of OmpRc could be useful in helping to define the positioning of the alpha
      subunit of RNA polymerase in relation to transcriptional activators that are
      bound to DNA.

PMID- 9016720
TI  - Cyclophilin A complexed with a fragment of HIV-1 gag protein: insights into HIV-1
      infectious activity.
AB  - BACKGROUND: Cyclophilin A (CyPA), a receptor of the immunosuppressive drug
      cyclosporin A, catalyzes the cis-trans isomerization of peptidyl-prolyl bonds and
      is required for the infectious activity of human immunodeficiency virus type 1
      (HIV-1). The crystal structure of CyPA complexed with a fragment of the HIV-1 gag
      protein should provide insights into the nature of CyPA-gag interactions and may
      suggest a role for CyPA in HIV-1 infectious activity. RESULTS: The crystal
      structure of CyPA complexed with a 25 amino acid peptide of HIV-1 gag capsid
      protein (25-mer) was determined and refined to an R factor of 0.195 at 1.8 A
      resolution. The sequence Ala88-Gly89-Pro90-Ile91 of the gag fragment is the major
      portion to bind to the active site of CyPA. Two residues of the 25-mer (Pro90
      Ile91) bind to CyPA in a similar manner to two residues (Pro-Phe) of the CyPA
      substrate, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (AAPF). However, the N
      terminus of the 25-mer (Ala88-Gly89) exhibits a different hydrogen-bonding
      pattern and molecular conformation than AAPF. The peptidyl-prolyl bond between
      Gly89 and Pro90 of the 25-mer has a trans conformation, in contrast to the cis
      conformation observed in other known CyPA-peptide complexes. The residue
      preceding proline, Gly89, has an unfavorable backbone conformation usually only
      adopted by glycine. CONCLUSIONS: The unfavorable backbone conformation of Gly89
      of the gag 25-mer fragment suggests that binding between HIV-1 gag protein and
      CyPA requires a special sequence, Gly-Pro. Thus, in HIV-1 infectivity, CyPA is
      likely to function as a chaperone, rather than as a cis-trans isomerase. However,
      the observation of similarities between the C termini of the 25-mer and the
      substrate AAPF means that the involvement of the cis-trans isomerase activity of
      CyPA cannot be completely ruled out.

PMID- 9016719
TI  - Crystal structure of a 30 kDa C-terminal fragment from the gamma chain of human
      fibrinogen.
AB  - BACKGROUND: Blood coagulation occurs by a cascade of zymogen activation resulting
      from minor proteolysis. The final stage of coagulation involves thrombin
      generation and limited proteolysis of fibrinogen to give spontaneously
      polymerizing fibrin. The resulting fibrin network is covalently crosslinked by
      factor XIIIa to yield a stable blood clot. Fibrinogen is a 340 kDa glycoprotein
      composed of six polypeptide chains, (alphabetagamma)2, held together by 29
      disulfide bonds. The globular C terminus of the gamma chain contains a fibrin
      polymerization surface, the principal factor XIIIa crosslinking site, the
      platelet receptor recognition site, and a calcium-binding site. Structural
      information on this domain should thus prove helpful in understanding clot
      formation. RESULTS: The X-ray crystallographic structure of the 30 kDa globular C
      terminus of the gamma chain of human fibrinogen has been determined in one
      crystal form using multiple isomorphous replacement methods. The refined
      coordinates were used to solve the structure in two more crystal forms by
      molecular replacement; the crystal structures have been refined against
      diffraction data to either 2.5 A or 2.1 A resolution. Three domains were
      identified in the structure, including a C-terminal fibrin-polymerization domain
      (P), which contains a single calcium-binding site and a deep binding pocket that
      provides the polymerization surface. The overall structure has a pronounced
      dipole moment, and the C-terminal residues appear highly flexible. CONCLUSIONS:
      The polymerization domain in the gamma chain is the most variable among a family
      of fibrinogen-related proteins and contains many acidic residues. These residues
      contribute to the molecular dipole moment in the structure, which may allow
      electrostatic steering to guide the alignment of fibrin monomers during the
      polymerization process. The flexibility of the C-terminal residues, which contain
      one of the factor XIIIa crosslinking sites and the platelet receptor recognition
      site, may be important in the function of this domain.

PMID- 9016721
TI  - Role REVersal: understanding how RRE RNA binds its peptide ligand.
AB  - The structure of a complex between the HIV Revresponsive element (RRE) RNA and a
      fragment of the Rev protein has recently been determined by NMR. Together with
      previous studies of the Tat-TAR complex, these results show how RNA elements with
      considerable tertiary structure are able to play a more active role in directing
      binding to elements of protein secondary structure.

PMID- 9016722
TI  - Two's company, three's a crowd: the yeast two hybrid system for mapping molecular
      interactions.

PMID- 9016723
TI  - The crystal structure of a major allergen from plants.
AB  - BACKGROUND: Profilins are small eukaryotic proteins involved in modulating the
      assembly of actin microfilaments in the cytoplasm. They are able to bind both
      phosphatidylinositol-4,5-bisphosphate and poly-L-proline (PLP) and thus play a
      critical role in signaling pathways. Plant profilins are of interest because
      immunological cross-reactivity between pollen and human profilin may be the cause
      of hay fever and broad allergies to pollens. RESULTS: The determination of the
      Arabidopsis thaliana profilin isoform I structure, using multiwavelength
      anomalous diffraction (MAD) to obtain structure-factor phases, is reported here.
      The structure of Arabidopsis profilin is similar to that of previously determined
      profilin structures. Conserved amino acid residues in profilins from plants,
      mammals, and lower eukaryotes are critically important in dictating the geometry
      of the PLP-binding site and the overall polypeptide fold. The main feature
      distinguishing plant profilins from other profilins is a solvent-filled pocket
      located in the most variable region of the fold. CONCLUSIONS: Comparison of the
      structures of SH3 domains with those of profilins from three distinct sources
      suggests that the mode of PLP binding may be similar. A comparison of three
      profilin structures from different families reveals only partial conservation of
      the actin-binding surface. The proximity of the semi-conserved actin-binding site
      and the binding pocket characteristic of plant profilins suggests that epitopes
      encompassing both features are responsible for the cross-reactivity of antibodies
      between human and plant profilins thought to be responsible for type I allergies.

PMID- 9016724
TI  - A new function for a common fold: the crystal structure of quinolinic acid
      phosphoribosyltransferase.
AB  - BACKGROUND: Quinolinic acid (QA) is a neurotoxin and has been shown to be present
      at high levels in the central nervous system of patients with certain diseases,
      such as AIDS and meningitis. The enzyme quinolinic acid phosphoribosyltransferase
      (QAPRTase) provides the only route for QA metabolism and is also an essential
      step in de novo NAD biosynthesis. QAPRTase catalyzes the synthesis of nicotinic
      acid mononucleotide (NAMN) from QA and 5-phosphoribosyl-1-pyrophosphate (PRPP).
      The structures of several phosphoribosyltransferases (PRTases) have been
      reported, and all have shown a similar fold of a five-strandard beta sheet
      surrounded by four alpha helices. A conserved sequence motif of 13 residues is
      common to these 'type I' PRTases but is not observed in the QAPRTase sequence,
      suggestive of a different fold for this enzyme. RESULTS: The crystal structure of
      QAPRTase from Salmonella typhimurium has been determined with bound QA to 2.8 A
      resolution, and with bound NAMN to 3.0 A resolution. Most significantly, the
      enzyme shows a completely novel fold for a PRTase enzyme comprising a two-domain
      structure: a mixed alpha/beta N-terminal domain and an alpha/beta barrel-like
      domain containing seven beta strands. The active site is located at the C
      terminal ends of the beta strands of the alpha/beta barrel, and is bordered by
      the N-terminal domain of the second subunit of the dimer. The active site is
      largely composed of a number of conserved charged residues that appear to be
      important for substrate binding and catalysis. CONCLUSIONS: The seven-stranded
      alpha/beta-barrel domain of QAPRTase is very similar in structure to the eight
      stranded alpha/beta-barrel enzymes. The structure shows a phosphate-binding site
      that appears to be conserved among many alpha/beta-barrel enzymes including
      indole-3-glycerol phosphate synthase and flavocytochrome b2. The new fold
      observed here demonstrates that the PRTase enzymes have evolved their similar
      chemistry from at least two completely different protein architectures.

PMID- 9016726
TI  - Women's cardiovascular health.
AB  - Significant coronary artery disease is uncommon in premenopausal women, but it is
      the leading cause of death among postmenopausal women. This article briefly
      discusses atherosclerotic disease in women, including the effects of menopause
      and estrogen, the role of cholesterol, hypertension, exercise and weight control,
      smoking cessation, and diabetes mellitus. The role of screening and testing for
      coronary artery disease and carotid artery stenosis is discussed. Recommendations
      for prevention and patient education are included in each section.

PMID- 9016727
TI  - Cancer prevention and screening in women.
AB  - Although there is no recommended screening for ovarian or endometrial cancers,
      the use of oral contraceptives is a primary prevention maneuver. The prevention
      of cervical cancer is accomplished best by Pap smear screening every 1 to 3
      years. Clinical breast examination and mammography every 1 to 2 years after age
      50 years are effective in reducing breast cancer mortality. Screening for BRCA1
      and BRCA2 mutations is now available, but the role of these tests is still not
      clear; extensive patient counseling is required.

PMID- 9016728
TI  - Osteoporosis in women.
AB  - Many preventive and treatment strategies are now available for osteoporosis,
      offering many women the opportunity to forego its many complications. Exercise
      with calcium and vitamin D supplements is recommended for most patients.
      Estrogens are a preferred treatment but not acceptable to many women.
      Alendronate, a bisphosphonate, recently became available to treat osteoporosis.
      Calcitonin, subcutaneous or intranasal, also can be useful.

PMID- 9016729
TI  - Care of adolescent girls.
AB  - Primary care of girls between the ages of 10 and 20 presents some unique
      challenges. This article presents a review of normal adolescent development and
      explores preventive health issues and some of the more common acute medical
      problems of adolescent girls. Counseling on some behavioral and psychosocial
      issues also is discussed. Finally, anticipatory guidance topics to be discussed
      with parents are included.

PMID- 9016730
TI  - Violence against women.
AB  - This article addresses two primary issues: partner violence and sexual assault.
      Partner violence refers to the infliction of harm by one intimate partner to the
      other, with the intention of causing pain or controlling the other's behavior.
      Sexual assault is sex without consent, obtained by force or threat. Sexual
      assault can be perpetrated by spouses, lovers, dates, relatives, parents,
      acquaintances, and strangers.

PMID- 9016731
TI  - Contraception and preconception counseling.
AB  - Contraception and preconception counseling are vital issues in women's health.
      This article reviews recent literature in both fields with an emphasis on
      clinical outcomes research. Satisfaction (which affects compliance), morbidity
      and mortality, and side effects of contraceptives are reviewed. Current
      literature on preconception counseling is discussed.

PMID- 9016732
TI  - Prenatal care.
AB  - Available evidence suggests that prenatal care has played an important role in
      reducing maternal and infant mortality. Medical surveillance throughout pregnancy
      is the foundation of prenatal care and should be enhanced by psychosocial
      support. Only tests and procedures shown to be useful should be performed.
      Patient education includes promotion of healthy behaviors, nutritional advice,
      and preparation for childbirth.

PMID- 9016733
TI  - Care of the breast and support of breast-feeding.
AB  - Primary care physicians can integrate care of the breasts through a woman's life
      cycle. Early and frequent nursing and careful attention to the infant's suckling
      position during the postpartum period can prevent several common problems.
      Neonatal jaundice, poor weight gain, mastitis, and candidiasis should be
      recognized and managed correctly. Outside the puerperium, fibrocystic change,
      nonlactational mastitis, and benign breast masses are encountered commonly.
      Problems related to silicone augmentation are discussed briefly.

PMID- 9016734
TI  - Dysmenorrhea and dysfunctional uterine bleeding.
AB  - Dysfunctional uterine bleeding is a diagnosis of exclusion. Endometrial cancer
      and endometrial precursor lesions must be excluded before a diagnosis of
      anovulatory bleeding is made. Treatment consists of intravenous estrogen therapy,
      oral contraceptive pills, and progestational agents. Menorrhagia is excessive
      menstrual bleeding treated with antiprostaglandins, levonorgestrel-releasing
      intrauterine contraceptive devices, endometrial ablation, and danazol.
      Dysmenorrhea results from the release of prostaglandin 2alpha and is treated with
      antiprostaglandin agents such as nonsteroidal anti-inflammatory drugs.

PMID- 9016735
TI  - Women's health. Sexually transmitted diseases.
AB  - When providing health care for women, one of the more common problems facing the
      primary care physician is sexually transmitted diseases (STDs). It is important
      to be able to develop an accurate diagnosis and appropriate treatment plan for
      STDs to reduce the potential long-term sequelae of these infections. It is also
      vital for the primary care physician to provide counseling for patients with STDs
      to improve compliance with the treatment regimens and prevent any further risk
      taking behavior.

PMID- 9016736
TI  - Basic infertility assessment.
AB  - Infertility is a problem commonly seen in the primary care office, affecting one
      in every six couples. Causes of infertility and basics of the infertility
      assessment are described in this article. Therapeutic options are discussed. The
      role of the primary care provider in the diagnosis, treatment, and support of the
      infertile couple is defined.

PMID- 9016737
TI  - Menopause.
AB  - Most women live long enough to become postmenopausal. Menopause is not a disease,
      but it can be associated with discomfort, a decreased quality of life, and an
      increase in the disease risks of osteoporosis and coronary heart disease. The
      onset of menopause is an excellent time for a women's primary care physician to
      assess her overall health and the need for health maintenance measures, which may
      include hormone replacement therapy.

PMID- 9016738
TI  - Overview of combustion toxicology.
AB  - Combustion toxicology embraces the nature, the severity, and the time course of
      adverse effects produced upon exposure to fire-generated toxic species. These
      species usually consist of narcotic toxicants or asphyxiants, along with those
      which may produce sensory/upper respiratory and even pulmonary irritation. They
      all act in concert to compromise the vital systems of those exposed, leading to
      incapacitation and death generally through various hypoxia-producing mechanisms.
      Some fire gas toxicants are material-dependent, some are largely dependent on the
      combustion conditions of the fire, while others may be dependent on both. Since
      the rates of generation of fire toxicants are powered by the energy release of
      the fire, the development of toxic hazard is also dependent on the fire itself.

PMID- 9016739
TI  - Behavioural impairment in smoke environments.
AB  - When aircraft cabin occupants are exposed to fire effluent, the first hazard
      encountered is usually smoke, containing particulates and toxic gases, which
      cause immediate visual obscuration and painful irritation of the eyes and
      respiratory tract. This may be followed by incapacitation due to pain or
      asphyxia, if exposure continues. In smouldering or small, confined, in-flight
      fires, where the yields of organic irritants and acid gases are likely to be high
      and exposure times long, then the distressing effects of irritants, lung
      inflammation, and asphyxia induced by carbon monoxide (CO) are likely to be the
      main hazards. For post-crash fires, which tend to develop rapidly to flashover,
      the time available for escape is often limited to a few minutes before conditions
      become lethal due to the effects of toxic smoke and heat, so that survival
      depends upon a rapid egress. Visual obscuration and smoke irritancy are important
      during the early stages in that they may reduce the speed and efficiency of
      escape. People have been shown to be reluctant to enter smoke-logged areas if
      these are between them and an exit, and movement speeds are greatly reduced at
      optical densities above OD/m 0.5, and even more when the smoke is irritant. Once
      cabin lining and seating materials become heavily involved in the area opposite a
      cabin breach, then the concentrations of toxic gases, especially CO and hydrogen
      cyanide, can increase rapidly further down the cabin causing rapid incapacitation
      of any remaining cabin occupants. This is followed or accompanied by extreme
      heat, so that deaths result from asphyxia and/or heat shock. For in-flight fires,
      it is recommended that consideration should be given to reducing the hazard from
      irritants. For post-crash fires, measures aimed at delaying the involvement of
      cabin contents (such as spray mist systems) should be considered.

PMID- 9016740
TI  - The management of aircraft passenger survival in fire.
AB  - The prime factors influencing survivability from 10 major fire-related public
      transport aircraft accidents were assessed. Regulatory requirements were assessed
      against derived criteria and alternate concepts evaluated to identify a preferred
      strategy for enhanced survival; the provision of passenger protective breathing
      equipment (PPBE) was part of the twin strategy selected. PPBE tests conducted by
      the UK Air Accidents Investigation Branch using lung simulators and semi
      controlled complex challenge combustion atmospheres generated from defined
      mixtures of cabin interior materials indicated that Hopcalite filters could
      provide satisfactory protection against carbon monoxide, hydrogen cyanide,
      hydrogen fluoride, hydrogen chloride, nitrogen oxides, sulphur dioxide, ammonia,
      acrolein, and other hydrocarbon compounds, for periods up to 30 min. Filtered
      levels of carbon dioxide (CO2) could be maintained within a 5% limit (inhaled
      atmosphere + dead space) against such atmospheres containing up to 4% CO2.
      Concentrations of oxygen downstream from the filters were up to some 1.0% above
      that present in the challenge atmospheres. Separate lung simulator tests on
      breathable gas (oxygen) hoods indicated that satisfactory respiratory protection
      could be provided for periods of up to 31 min. A possible filter modification of
      the passenger oxygen mask concept is discussed. It is recommended that research
      should be emphasized on the development of a means (e.g. PPBE) for providing in
      flight smoke protection for passengers.

PMID- 9016741
TI  - Computer modelling of human behaviour in aircraft fire accidents.
AB  - The mathematical simulation of the evacuation process has a wide and largely
      untapped scope of application within the aircraft industry. The function of the
      mathematical model is to provide insight into complex behaviour by allowing
      designers, legislators, and investigators to ask 'what if' questions. Such a
      model, EXODUS, is currently under development, and this paper describes its
      evolution and potential applications. EXODUS is an egress model designed to
      simulate the evacuation of large numbers of individuals from an enclosure, such
      as an aircraft. The model tracks the trajectory of each individual as they make
      their way out of the enclosure or are overcome by fire hazards, such as heat and
      toxic gases. The software is expert system-based, the progressive motion and
      behaviour of each individual being determined by a set of heuristics or rules.
      EXODUS comprises five core interacting components: (i) the Movement Submodel --
      controls the physical movement of individual passengers from their current
      position to the most suitable neighbouring location; (ii) the Behaviour Submodel 
      - determines an individual's response to the current prevailing situation; (iii)
      the Passenger Submodel -- describes an individual as a collection of 22 defining
      attributes and variables; (iv) the Hazard Submodel -- controls the atmospheric
      and physical environment; and (v) the Toxicity Submodel -- determines the effects
      on an individual exposed to the fire products, heat, and narcotic gases through
      the Fractional Effective Dose calculations. These components are briefly
      described and their capabilities and limitations are demonstrated through
      comparison with experimental data and several hypothetical evacuation scenarios.

PMID- 9016742
TI  - Application of full-scale fire tests to characterize and improve the aircraft
      postcrash fire environment.
AB  - The Federal Aviation Administration (FAA) has conducted numerous full-scale fire
      tests for the purpose of characterizing the postcrash cabin fire environment and
      developing improved fire test criteria for cabin materials. The tests
      consistently demonstrated the importance of cabin flashover on occupant
      survivability. Flashover is basically a sudden, very rapid spread of fire,
      generating large quantities of heat, smoke, and toxic gases that quickly fill the
      cabin. Before flashover, the cabin environment is largely survivable; after
      flashover, occupant survival becomes highly unlikely. Thermal incapacitation is
      more important near the fire origin and at higher elevations, whereas toxic gas
      incapacitation is predominant away from the fire origin and at lower elevations.
      The FAA has developed and adopted improved fire test methods for seat cushions
      (fire blocking layers) and interior panels (low heat release). In both cases, the
      fire test methods are consistent with full-scale test results and serve to
      improve occupant survivability by delaying the onset of flashover, thereby
      providing substantially greater available time for occupant evacuation.

PMID- 9016743
TI  - New research avenues in toxicology: 7-gas N-Gas Model, toxicant suppressants, and
      genetic toxicology.
AB  - Three research areas -- a 7-gas N-Gas Model, toxicant suppressants, and genetic
      toxicology -- are presented as new research approaches in toxicology. The current
      6-gas N-Gas Model predicts the toxic potency of the combustion products of
      materials based on the toxicological interactions of the fire gases carbon
      monoxide (CO), carbon dioxide (CO2), low oxygen (O2) concentrations, hydrogen
      cyanide (HCN), hydrogen chloride, and hydrogen bromide. The present research
      includes nitrogen dioxide (NO2) in a new 7-gas model which incorporates the
      synergistic effects of NO2 and CO2, the antagonistic effects of NO2 and HCN, and
      the additive effects of NO2 with CO and low O2. The area of toxicant suppressants
      concerns chemicals, which when added to a material, will inhibit or reduce the
      concentration of a specific toxic gas normally generated during thermal
      decomposition of that material. The effectiveness of this approach was
      demonstrated at the US National Institute of Standards and Technology when HCN
      generation was reduced by 90% and the resultant toxicity of the combustion
      products was lowered by 50% when a flexible polyurethane (FPU) foam was treated
      with 0.1% (by weight) cuprous oxide (Cu2O). Although melamine-treated FPU foams
      are being promoted as more fire safe than standard foams, a melamine-treated foam
      generated 10 times more HCN than a foam without melamine. The addition of Cu2O to
      this melamine foam also reduced the HCN generation by 90%. The genetic toxicology
      research entails the examination of DNA damage that results from the exposure of
      human cells to various environmental toxicants and gases.

PMID- 9016744
TI  - An overview of the development, validation, and application of neurobehavioral
      and neuromolecular toxicity assessment batteries: potential applications to
      combustion toxicology.
AB  - Currently, there are few alternatives to the use of animals in toxicology for
      human risk assessment. Neurobehavioral toxicology is an emerging area in which
      complex performance capacity is evaluated during or following toxicological
      exposure. While a number of single tests and a few more complex neurobehavioral
      batteries exist, no fully validated and comprehensive neurobehavioral toxicity
      assessment battery has yet been developed. The Neurobehavioral Toxicity
      Assessment Battery (NTAB) is a multi-test battery being developed by the Naval
      Medical Research Institute Detachment (Toxicology) (NMRI/TD) to categorize the
      potential neurobehavioral toxicity of compounds of Navy interest, especially
      those found in combustion atmospheres. The NTAB is intended to identify specific
      areas of deficit (e.g. motivational, sensory, motor, and cognitive) from complex
      changes in performance induced by toxic exposures, as well as to provide a
      mechanism to evaluate recovery of neurobehavioral integrity. Portions of the NTAB
      have been successfully used to assess the risk of brief exposure to low
      concentrations of combustion gases, including smoke from electrical aircraft
      fires, ozone-depleting substances and their replacements, and the novel
      neuroconvulsant trimethylolpropane phosphate. The goal of the NMRI/TD
      Neurobehavioral Toxicology Group and the Tri-Service Toxicology Consortium's
      neurobehavioral toxicology program is the incorporation of more molecular
      techniques involving neurophysiology, neuropharmacology, in vivo
      electrochemistry, and real-time microdialysis for correlative use with the
      neurobehavioral battery in human risk assessment. This overview discusses the
      application of neurobehavioral and neuromolecular endpoint test batteries to
      combustion toxicology.

PMID- 9016745
TI  - Reactions to particles in smoke.
AB  - Smoke is a mixture of particles and gaseous chemicals of varying physical and
      chemical properties. When inhaled these produce the characteristic features of
      smoke-inhalational injury. Although heat is produced in fires it is the chemical
      agents which cause the damage to the airways and the lungs. Mortality and
      morbidity are closely related to pulmonary injury and thus to the particulate and
      chemical nature of smoke. Moreover, there seems to be a potentiating effect, in
      that the particles worsen the toxicity of the chemicals present.

PMID- 9016746
TI  - Predicted combustion product deposition in the human airway.
AB  - Fires involving modern polymeric materials produce toxic vapours and particles of
      widely varying composition and size depending on available oxygen and localized
      temperatures. Adverse health effects of inhaled combustion-generated particles
      depend on physiological interactions at the airway deposition site. The present
      work is a theoretical investigation into the importance of airway humidity and
      temperature profiles, initial particle size, particle size distribution and ionic
      concentration on airway particle deposition. A modified numerical model
      accounting for hygroscopic particle growth was used to predict airway deposition
      of 0.1-10.0 microm mass median aerodynamic diameter (MMAD) particles. Dynamic
      humidity profiles were generated with an unsteady state model of heat and water
      vapour transport. Results suggest that for hygroscopic particles < 2.0 microm,
      MMAD dynamic end-inspiratory humidity profiles produce up to 250% greater
      predicted nasopharyngeal deposition than steady state humidity profiles. Assuming
      combustion products are hygroscopic, these results also suggest that less
      pulmonary deposition will occur than previously predicted. In addition, higher
      upper airway concentrations of combustion products may have significant health
      consequences independent of pulmonary deposition patterns.

PMID- 9016748
TI  - In-flight cabin smoke control.
AB  - Fatal accidents originating from in-flight cabin fires comprise only about 1% of
      all fatal accidents in the civil jet transport fleet. Nevertheless, the
      impossibility of escape during flight accentuates the hazards resulting from low
      visibility and toxic gases. Control of combustion products in an aircraft cabin
      is affected by several characteristics that make the aircraft cabin environment
      unique. The aircraft fuselage is pressurized in flight and has an air
      distribution system which provides ventilation jets from the ceiling level air
      inlets running along the cabin length. A fixed quantity of ventilation air is
      metered into the cabin and air discharge is handled primarily by pressure
      controlling outflow valves in the rear lower part of the fuselage. Earlier
      airplane flight tests on cabin smoke control used generators producing minimally
      buoyant smoke products that moved with and served as a telltales for overall
      cabin ventilation flows. Analytical studies were done with localized smoke
      production to predict the percent of cabin length that would remain smoke-free
      during continuous generation. Development of a buoyant smoke generator allowed
      simulation of a fire plume with controllable simulated temperature and heat
      release rates. Tests on a Boeing 757, modified to allow smoke venting out through
      the top of the cabin, showed that the buoyant smoke front moved at 0.46m/s
      (1.5ft/sec) with and 0.27m/sec (0.9ft/sec) against, the axial ventilation
      airflow. Flight tests in a modified Boeing 727 showed that a ceiling level
      counterflow of about 0.55m/sec (1.8ft/sec) was required to arrest the forward
      movement of buoyant smoke. A design goal of 0.61m/s (2ft/sec) axial cabin flow
      would require a flow rate of 99m3/min (3500ft3/min) in a furnished Boeing 757.
      The current maximum fresh air cabin ventilation flow is 78m3/min (2756 ft3/min).
      Experimental results indicate that buoyancy effects cause smoke movement
      behaviour that is not predicted by traditional design analyses and flight test
      methodologies. Augmenting available ventilation for smoke control remains a
      design and safety challenge.

PMID- 9016747
TI  - Methodologic considerations in the interpretation of postmortem carboxyhemoglobin
      concentrations.
AB  - The interpretation of postmortem carboxyhemoglobin (COHb) concentrations can have
      major implications even when COHb is not the direct cause of death. Much
      litigation may hinge on the length of time an individual was alive during the
      fire. Therefore, the reliability of an analytical method to measure COHb, ranging
      from low to sub-lethal levels, is critical to the proper interpretation of
      results. This study used 40 blood specimens from fire deaths and 15 blood
      specimens from non-fire deaths to compare COHb levels obtained from a
      spectrophotometric method (IL 482 CO-Oximeter; CO-Ox) with a reference gas
      chromatographic method (GC). Since spectrophotometric methods are influenced by
      the amount of total hemoglobin (Hb) present in the blood, multiple saline
      dilutions of specimens were performed to yield Hb as low as 1g/dl. For GC COHb
      concentrations < 5% and Hb > or = 4g/dl, the average and median ratios of CO-Ox
      COHb to GC COHb concentrations were 2.8 and 2.6 respectively. These ratios were
      8.0 and 6.8 respectively when Hb < 4g/dl. At GC COHb levels ranging from 5 to 40%
      and Hb > or = 4g/dl, the average and median ratios were 1.6 and 1.0 respectively.
      These ratios were correspondingly 2.1 and 1.9 when Hb < 4 g/dl. These data
      clearly indicate COHb can be influenced by the analytical methods used.

PMID- 9016749
TI  - Ventilation effects on combustion products.
AB  - The effects of fire ventilation on combustion products are expressed in terms of
      relationship between concentration of products and equivalence ratio, phi. For
      well-ventilated fires, phi < 1.0, where mostly heat and products of complete
      combustion (such as CO2 and water) are generated. For ventilation-controlled
      fires, phi > 1.0, where mostly products of incomplete combustion are generated
      with very high concentrations in a transition region for phi between 1.0 and 3.5.
      The high concentrations of the products of incomplete combustion are dangerous to
      life and property. For halogenated materials, this condition occurs for phi <
      1.0. The non-flaming region for fires is found to exist for phi > 3.5.
      Correlations have been developed for the prediction of concentrations of products
      at various phi values for the assessment of combustion toxicity and smoke damage
      hazards by zone fire models, such as Hazard 1. The correlations show good
      agreement with the measured concentrations. The concentrations of the products of
      incomplete combustion depend on the chemical structures of the materials. For the
      same phi values, the carbon monoxide concentrations are higher for materials with
      oxygen atoms in the structure, whereas smoke concentrations are higher for
      materials with carbon and hydrogen atoms in the structure. The results of the
      study suggest that it is necessary to examine the combustion behaviour of
      advanced materials for use in aircraft and other critical applications at various
      phi values, along with the toxicity experiments.

PMID- 9016750
TI  - Evaluation of lethality estimates for combustion gases in military scenarios.
AB  - To meet the military objective of determining criteria for incapacitation and
      lethality from toxic gas exposures, a series of small animal tests and data
      analyses were conducted. Carbon monoxide (CO), a narcotic gas and nitrogen
      dioxide (NO2), an irritant gas, along with carbon dioxide (CO2) were tested
      individually and in the following mixtures: (CO + CO2), (NO2 + CO2) and (NO2 + CO
      + CO2). A group of six animals was exposed to each of the gases and their
      combinations, lethality and biophysical data were collected. We conclude that our
      observations of lethality from single toxic gases can be correlated with a
      fractional effective dose (FED) description, in which external concentrations are
      corrected for minute volume changes. Multiple gas exposures clearly demonstrate
      synergistic effects because lethality rates greatly exceed those expected from
      statistically independent causes. Simple addition of the FED values, however,
      overstates the effect and implies a competition between the narcotic and irritant
      gas effects. The N-Gas model, while being an additive FED model, does not appear
      to be in a form that could guide the setting of military exposure standards.

PMID- 9016751
TI  - Fractional effective dose model for post-crash aircraft survivability.
AB  - The development of a survival model for post-crash aircraft cabin fires is
      described in this paper. Its development is based on an extensive review of the
      literature on the toxicity of combustion gases and on thermal hazards. This model
      is to be used as a predictive tool to gauge human survivability in full scale
      aircraft cabin fire tests. The extensive literature search was conducted for
      carbon monoxide (CO), carbon dioxide (CO2), hydrogen cyanide (HCN), low oxygen,
      hydrogen fluoride (HF), hydrogen chloride (HCl), hydrogen bromide (HBr), nitrogen
      dioxide (NO2), sulfur dioxide (SO2), acrolein (CH2CHCHO), and heat exposures.
      Those studies by various investigators of exposures to single and mixed gases on
      humans, primates, rats, and mice at different physical activity levels were
      compared. Regression equations were derived from those studies to give the best
      fit to the gas exposure concentration and duration data. The equation judged to
      best model the human escaping from an aircraft cabin was selected for each gas.
      This survival model uses incapacitation data to obtain a fractional effective
      dose (FED) for incapacitation (FED(I)) and lethality data, inclusive of post
      exposure deaths, to obtain a FED for lethality (FED(L)). The exposure time
      required for either FED(I) or FED(L) to reach unity, using a projected set of gas
      concentrations, represents the exposure time available to escape from the
      specified fire environment or to survive post exposure, respectively. The effect
      of CO2 in increasing the uptake of other gases was factored into the
      concentration term in the FED equation for all gases with the exception of CO2
      and oxygen. Higher respiratory minute volumes due to CO2 exposure were found to
      be an important factor in predicting the time available to escape. This FED-based
      model can be applied to the evaluation of the toxicity of smoke in computer
      modeling of aircraft fire situations.

PMID- 9016752
TI  - Situational smoke toxicity testing: hazard assessment as the 'front end' of a
      smoke toxicity test.
AB  - Traditionally, the toxic potency of the smoke from a material or product is part
      of the assessment of the fire hazard in a given scenario. The assessment also
      requires a knowledge of virtually all the details of the fire environment and,
      until they are identified, a 'safe' or 'acceptable' level of smoke toxicity is a
      term without meaning. This paper suggests a method of using the knowledge of
      these factors to simplify smoke toxicity testing. Faster, cheaper, and better
      targeted smoke toxicity tests would result if the rest of the hazard assessment
      were carried out first. This is accomplished by determining or specifying all the
      relevant fire properties except the toxic potency, identifying the other
      environmental conditions (such as those typical of an aircraft cabin interior)
      and the desired tenability limits (such as the minimum necessary escape time),
      and then solving the equations for the buildup of toxic conditions in terms of
      the single remaining unknown, the toxic potency. The result is the greatest toxic
      potency which would meet the requirements of the analysis. In this approach, a
      material or product is acceptable if its smoke is no more toxic then the computed
      result and unacceptable if it is not. It would not be necessary to obtain an EC50
      (product concentration which will cause an effect in half the animals) or dose
      response profile, only the response at whatever dose is dictated by the analysis.
      Two sample cases are presented to illustrate the technique.

PMID- 9016753
TI  - New research avenues in combustion toxicology.

PMID- 9016754
TI  - Smoke toxicity 'standard' test method for materials.

PMID- 9016755
TI  - Effects of a diet deficient in tyrosine and queuine on germfree mice.
AB  - A chemically-defined diet consisting of amino acids (including tyrosine),
      vitamins, trace elements, glucose, etc., known to support growth and reproduction
      through many generations when fed to germfree mice has been in use for many years
      in our laboratory. Classical nutritional studies showed that tyrosine was not a
      dietary requirement for higher mammals if an adequate amount of phenylalanine was
      present. Therefore, it was unexpected that when tyrosine was removed from this
      diet, the germfree mice developed ocular, neurological and other abnormalities
      which resulted in 100% fatalities usually within two weeks. Adding tyrosine back
      to the diet prevented the abnormalities from occurring. Conventional mice with a
      normal intestinal flora showed none of these symptoms when fed the same tyrosine
      deficient diet. We added queuine to the tyrosine-deficient diet at a
      concentration of 0.1 microM. The germfree mice that were fed the diet
      supplemented with queuine were asymptomatic and remained alive until the
      termination of the experiments.

PMID- 9016757
TI  - Characterization of scFv-421, a single-chain antibody targeted to p53.
AB  - A gene encoding a single-chain antibody (scFv) which specifically binds the tumor
      suppressor protein p53 has been constructed from RNA of hybridoma cells producing
      Pab 421. scFv-421 which was expressed and purified from bacteria specifically
      binds p53. scFv-421, as well as the previously described scFv-FRP5 and -R1R (1),
      were expressed intracellularly in mammalian cells and targeted to different
      subcellular locations, including the nucleus, cytoplasm, and endoplasmic
      reticulum (ER). High levels of all ER targeted scFv proteins, but not nuclear or
      cytoplasmic targeted proteins, were found in transfected COS-1 cells. In an
      attempt to stabilize the proteins, sequences encoding the mouse immunoglobin CK
      constant domain were added to each scFv construct. This led to a moderate
      increase in the cytoplasmic expression of scFv-FRP5.

PMID- 9016756
TI  - TNF can directly induce the expression of ubiquitin-dependent proteolytic system
      in rat soleus muscles.
AB  - Incubation of isolated rat soleus muscles in the presence of human recombinant
      TNF-alpha (10,000 U/ml) resulted in an important increase in ubiquitin gene
      expression (over 50%). Although previous studies involving cytokine
      administration in vivo (1) have demonstrated an action on ubiquitin-dependent
      proteolysis, this is the first report demonstrating a direct action of the
      cytokine on protein breakdown in incubated rat skeletal muscle.

PMID- 9016758
TI  - Caffeine- and inositol 1,4,5-trisphosphate-induced 45Ca2+ releases in the
      microsomes of tracheal epithelial cells.
AB  - Major parts of microsomes prepared from the epithelial cells of porcine trachea
      were tight-sealed vesicles since they showed a saturation of 45Ca2+ uptake and
      spontaneous releases of stored 45Ca2+ by the treatments of Ca2+-ionophore and
      Ca2+ channel agonists. In the presence of caffeine (10 mM), the maximal release
      of microsomal 45Ca2+ was observed at the extramicrosomal Ca2+ concentrations
      between 0.1 approximately 1 microM and at below or above this range of Ca2+
      concentration the releases were decreased, forming a bell-shaped curve. These
      results indicate that the microsomal 45Ca2+ releases were mediated by ryanodine
      receptor, a caffeine-sensitive Ca2+ channel. Caffeine (10 mM) released 30.2 +/-
      5.9% of microsomal 45Ca2+ while inositol 1,4,5-trisphosphate (InsP3, 10 microM)
      released 18.4 +/- 3.0% of the stored 45Ca2+. Caffeine-induced and InsP3-induced
      45Ca2+ releases were additive, implying that these two types of 45Ca2+ releases
      are from physically distinct microsomes. Procaine, an antagonist of ryanodine
      receptor, selectively blocked the effect of caffeine but not the effect of InsP3.
      The results suggest that the epithelial cells of porcine trachea have caffeine
      sensitive Ca2+ store in addition to InsP3-sensitive one.

PMID- 9016759
TI  - Possible involvement of Bcl-2 pathway in retinoid X receptor alpha-induced
      apoptosis of HL-60 cells.
AB  - Retinoids induce granulocytic differentiation and subsequent apoptosis in human
      myeloid (HL-60) leukemia cells. Differentiation is induced due to activation of
      retinoic acid receptors (RARs) whereas, activation of retinoid X receptors (RXRs)
      seems to be essential for driving these cells into apoptosis. In order to
      understand the mechanism of RXR induced apoptosis, we used a variant HL-60 cell
      line (HL-60R) with a transdominant negative mutation. The retroviral vector
      mediated gene transfer was used to introduce the functional RARs or RXR alpha
      into HL-60R cells. We studied the effect of receptor-selective retinoid treatment
      on the expression of Bcl-2 and Bax oncogenes by reverse-transcription polymerase
      chain reaction (RT-PCR) and immunoblot analysis in RARs and RXR alpha transfected
      HL-60 cells. Our results show that activation of RXR alpha results in apoptosis
      via down-modulation of Bcl-2 mRNA as well as its gene product expression with no
      change in Bax mRNA expression.

PMID- 9016760
TI  - Effect of concentration on the cytotoxic mechanism of doxorubicin--apoptosis and
      oxidative DNA damage.
AB  - Anthracycline derivatives such as doxorubicin are part of many chemotherapeutic
      regimens and reach peak plasma concentrations of 5 microM. We investigated the
      cytotoxic mechanisms of various doxorubicin concentrations in MOLT-4 ALL-cells.
      Concentrations of up to 100 microM doxorubicin achieved similar cytotoxic effects
      in cultures of MOLT-4 cells, but acted via different mechanisms. Doxorubicin
      induced apoptosis (maximum effect at 1 microM), which was dependent on RNA
      synthesis and involved oxidative stress. Concentrations higher than 3 microM did
      not induce apoptosis, but significantly inhibited RNA synthesis. DNA strand
      breaks in MOLT-4 cells occurred in the presence of 1 to 5 microM doxorubicin to a
      similar extent, but showed a dose-dependence at higher concentrations. There was
      no GC/MS-detectable oxidation of DNA bases in apoptotic cells and only 1 out of
      13 DNA base oxidation products, 8-hydroxyguanine, increased significantly in the
      presence of as much as 100 microM doxorubicin. These results suggest that at
      pharmacologically relevant concentrations apoptosis and not oxidative DNA damage
      is the main killing mechanism of doxorubicin against ALL-cells.

PMID- 9016761
TI  - Pulsatile Ca2+ influx in human neutrophils undergoing CD11b/CD18 integrin
      engagement.
AB  - Rapid-time confocal scanning has demonstrated that neutrophils undergoing
      CDllb/CD18 integrin-dependent adhesion show repeated elevations in cytosolic free
      Ca2+ concentration, due to Ca2+ influx. The magnitude of each individual influx,
      compared to the previous one, depended upon the time between the two, and not
      upon the cytosolic Ca2+ concentration at the start of the influx. Influx events
      occurring less than 100 seconds after the previous Ca2+ rise were observed not to
      reach the concentration of the preceding peak, whilst events occurring later
      usually exceeded the magnitude of the previous Ca2+ concentration. This suggested
      temporary inactivation, followed by recovery, of the Ca2+ influx mechanism. In
      addition, Ca2+ influx was most likely to occur immediately following this
      recovery. The involvement of Ca2+ store release at the site of integrin
      engagement suggested that the cytoskeletal connection between the peripheral
      store and membrane was facilitating the signalling of Ca2+ influx.

PMID- 9016762
TI  - 14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase.
AB  - To identify proteins which bind to mouse wee1 kinase, the yeast "two-hybrid"
      system was used with a mouse cDNA library. Using the carboxyl half of weel
      kinase, the 14-3-3 zeta protein was isolated. Recombinant 14-3-3 zeta was
      demonstrated to bind to wee1 kinase in vitro. The wee1 kinase phosphorylated by
      cdc2 kinase also bound to 14-3-3 zeta protein. When both wee1 kinase and 14-3-3
      zeta were transfected into COS-1 cells, they formed a complex in a cell. The
      sequence of wee1 kinase necessary for the binding was tested by a two hybrid
      system expressing different lengths of peptides derived from wee1 kinase. Both
      the entire kinase domain and a sequence in the carboxyl terminus was thought to
      be necessary for the binding. The function of 14-3-3 zeta protein remained to be
      elucidated in relation to the regulation of G2 to M phase transition through wee1
      kinase.

PMID- 9016763
TI  - Tyrosine phosphorylation of ErbB4 is stimulated by aurintricarboxylic acid in
      human neuroblastoma SH-SY5Y cells.
AB  - Aurintricarboxylic acid (ATA) has been reported to protect PC12 cells and
      cultured neuronal cells from serum starvation-induced cell death, and hippocampal
      neurons from N-methyl D-aspartate- or ischemia-induced cell death in vivo. We
      have found that ATA activated tyrosine phosphorylation cascade in PC12 cells as
      growth factors. Here, we report that ATA prevents cell death under serum
      starvation and induces tyrosine phosphorylation also in human neuroblastoma SH
      SY5Y cells. Furthermore, it was found that erbB4, a member of epidermal growth
      factor receptor family, is tyrosine-phosphorylated in response to ATA. Both,
      erbB4 and its ligand, neu differentiation factor (NDF)/ heregulin family, have
      been reported to be expressed abundantly in nervous system. Thus, tyrosine
      phosphorylation of erbB4 might explain the neuro-protective activity of ATA.

PMID- 9016764
TI  - A novel function of transferrin as a constituent of macromolecular activators of
      phagocytosis from platelets and their precursors.
AB  - Macromolecular activators of phagocytosis from platelets (MAPP:s-MAPP, 1500kDa
      and 1-MAPP, 300kDa) are glycoproteins released from human platelets and activate
      leukocyte phagocytosis via the Fc gamma receptors. Their production can be shown
      in CPD-stored platelets which have lost MAPP releasing activity by incubation
      with plasma-derived precursos of MAPP (pre-MAPP : pre-s-MAPP, 150kDa and pre-l
      MAPP, 300kDa) in the presence of Ca++. Partial amino acid sequence analysis of s
      MAPP revealed that it had homogeneity with transferrin (TF). Affinity
      chromatography using anti TF immunosorbent column showed that all of pre-MAPP and
      MAPP had immunoreactivity with anti TF antibodies. S-MAPP and 1-MAPP rich
      preparations from platelet release products lost their activity after treatment
      with ATP at acidic pH, in which condition iron atoms could be removed from holo
      transferrin molecules. In the experiment using polymerized TF and stored
      platelets, it was shown that platelets incubated with dimer and tetramer TF could
      produce MAPP function. These results suggest that dimer and tetramer transferrin
      are precursors of s-MAPP and 1-MAPP, respectively and that iron atoms are
      necessary for their phagocytosis activating function.

PMID- 9016765
TI  - 4-Hydroxynonenal interaction with rhodopsin.
AB  - 4-Hydroxynonenal binds easily to rhodopsin and this was accompanied by a decrease
      in measurable sulfhydryl groups. Analysis of tryptic digests of the rhodopsin-HNE
      adduct by high performance liquid chromatography revealed that several peptides
      present in the digests of rhodopsin disappeared, whereas HNE modified peptides
      not originally present were found in digests of the rhodopsin-HNE adduct. Matrix
      assisted laser desorption time of flight mass spectrometry showed that up to ten
      molecules of HNE bound to rhodopsin.

PMID- 9016766
TI  - Purification and characterization of recombinant baculovirus-expressed mouse DNA
      methyltransferase.
AB  - DNA methylation is essential for normal embryonic development in mice. An
      understanding of how DNA methylation is controlled is largely dependent upon the
      isolation and characterization of the cellular components of the DNA methylation
      system. The enzyme which methylates DNA in eukaryotic cells is a C-5 cytosine DNA
      methyltransferase. Historically, the characterization of this enzyme has been
      limited by its availability and purity. Here, we present a single-step
      purification of 4 mg of baculovirus-expressed mouse DNA methyltransferase
      containing a nickel-affinity leader peptide. The recombinant DNA
      methyltransferase copurified with inhibitory RNA which was removed by treatment
      with ribonuclease A. Like its non-recombinant counterpart, the recombinant enzyme
      is activated by hemi-methylation. A direct steady-state kinetic comparison
      between the recombinant baculovirus-expressed enzyme with its MEL cell-derived
      counterpart is presented.

PMID- 9016767
TI  - Construction of cDNA libraries from small amounts of total RNA using the
      suppression PCR effect.
AB  - Here we describe a method for preparing high-quality cDNA libraries from total
      RNA. By this method, double-stranded (ds) cDNA ligated with a specially designed
      ds adaptor is amplified by PCR using a modified T-primer and another primer
      corresponding to the outer part of the adaptor. The suppression PCR effect
      strongly inhibits the amplification of poly(A) RNA, thereby reducing background.
      This method leads to amplification of high-quality cDNA, facilitating the
      construction of representative cDNA libraries from as little as 10-100 ng of
      total RNA.

PMID- 9016768
TI  - Aspartate 196 in the first extracellular loop of the human VIP1 receptor is
      essential for VIP binding and VIP-stimulated cAMP production.
AB  - VIP receptors belong to a subfamily of G protein-coupled receptors that includes
      secretin, glucagon, PTH and several other receptors. We have used site-directed
      mutagenesis to investigate the requirement of some highly conserved residues in
      the extracellular loops including aspartate 196 (mutant D196A), leucine 199
      (mutant L199A), tryptophane 286 (mutant W286A) and tryptophane 294 (mutant W294A)
      for the ability of the human VIP1 receptor to bind VIP and to mediate VIP
      stimulated cAMP production. After transfection of mutated cDNAs in Cos-7 cells,
      it appeared that 1) mutants L199A, W286A and W294A bound VIP with the same
      dissociation constant as the wild-type receptor whereas mutant D196A did not bind
      125I-VIP; 2) mutants L199A, W286A and W294A mediate VIP-stimulated cAMP
      production with the same EC50 as the wild-type receptor whereas VIP displayed a
      500-fold decrease of potency in promoting cAMP production through mutant D196A.
      Since all mutated receptor proteins were expressed and delivered at the plasma
      membrane (immunofluorescence studies), it is concluded that the first
      extracellular loop of the human VIP1 receptor contains a highly conserved
      aspartate residue which is essential for VIP binding and VIP-stimulated cAMP
      production.

PMID- 9016769
TI  - Purification of the human RARgamma ligand-binding domain and crystallization of
      its complex with all-trans retinoic acid.
AB  - A 28-kDa fragment (residues 178-423) of the human retinoic acid receptor gamma,
      hRARgamma D3E, encompassing the ligand-binding domain (LBD) was overproduced in
      Escherichia coli and purified as a monomer to more than 95% purity and
      homogeneity. The Kd for all-trans retinoic acid binding was 0.6 +/- 0.1 nM.
      Crystals of the LBD complexed with all-trans retinoic acid were grown at pH 7
      from sodium acetate in the presence of detergents using the vapor diffusion
      method. They diffract to 2.0 A using a synchrotron radiation (lambda=0.91 A) and
      belong to the tetragonal space group P4(1)2(1)2 with unit cell parameters
      a=b=60.6 A and c=155.3 A, one monomer per asymmetric unit, a solvent content of
      ca. 33%, and a Vm value of approximately 2 A3/dalton.

PMID- 9016770
TI  - DNA polymerase epsilon from Drosophila melanogaster.
AB  - We identified a DNA polymerase species in Drosophila melanogaster embryos, and
      purified it. This polymerase shared some common properties with DNA polymerase
      epsilon from mammals and yeast as follows; it has a preference for
      poly(dA)/oligo(dT) as a template/primer, it is highly processive in DNA
      synthesis, it co-fractionates with 3'-5' exonuclease activity, it is sensitive to
      aphidicolin and is resistance to ddTTP. The polymerase activity was inhibited in
      the immuno-precipitation assay with anti-pol-epsilon antibodies, which were
      produced against a polypeptide coded on the cDNA of a putative Drosophila pol
      epsilon we isolated previously. Using these antibodies, Western blot analysis
      revealed that this polymerase is a 250kDa polypeptide, which is the same size as
      observed in mammals and yeast. These results indicate that Drosophila produces
      the epsilon-class of DNA polymerase, and like mammals or yeast, possesses the 5
      typical classes of DNA polymerases (alpha to epsilon) in its embryos.

PMID- 9016771
TI  - Phosphoinositide signalling in nuclei of Friend cells: DMSO-induced
      differentiation reduces the association of phosphatidylinositol-transfer protein
      with the nucleus.
AB  - Friend erythroleukemia cells have a nuclear phosphoinositide cycle which is
      related to both mitogen-stimulated cell growth and erythorid differentiation.
      Because of the important role of the phosphatidylinositol-transfer protein (PI
      TP) in phosphatidylinositol 4,5-bisphosphate (PtdInsP2) synthesis, we have
      analysed nuclei isolated from Friend cells for the presence of PI-TP. By Western
      Blotting it was demonstrated that both intact nuclei and nuclei deprived of the
      outer membrane contained the PI-TP alpha isoform. Upon induction of erythroid
      differentiation by DMSO, the amount of nuclear PI-TP alpha was greatly
      diminished. As shown previously, under these same conditions, nuclear
      phospholipase C beta1 (PLC beta1) is down-regulated as well.

PMID- 9016772
TI  - Expression of Sulfolobus solfataricus trpE and trpG genes in E. coli.
AB  - The genes trpE and trpG of the hyperthermophilic archaeon Sulfolobus
      solfataricus, encoding the components I and II of anthranilate synthase, were
      cloned and co-expressed in Escherichia coli. The properties of the recombinant
      protein were determined and compared to those of the wild type complex. Gel
      filtration chromatography revealed an alpha2beta2 composition. The heteromeric
      enzyme is fully active above 85 degrees C and can be considered to be an
      "extremozyme" according to Adams et al.[1]. Sulfolobus solfataricus anthranilate
      synthase is subject to feedback inhibition by L-tryptophan even if it lacks the
      co-operativity that has been observed for all the other tetrameric anthranilate
      synthases.

PMID- 9016773
TI  - Adrenomedullin stimulates cAMP accumulation and inhibits atrial natriuretic
      peptide gene expression in cardiomyocytes.
AB  - Adrenomedullin (ADM) is a novel vasodilating and natriuretic peptide which may
      play an important role in cardiovascular regulation. In neonatal cardiomyocyte
      cultures we have shown that ADM leads to dose-dependent inceases in cAMP
      accumulation and subsequent inhibition of atrial natriuretic peptide (ANP) gene
      expression and secretion. Forskolin-mediated elevation of intracellular cAMP
      levels led to a qualitatively similar inhibitory effect on both ANP gene
      expression and secretion. These data show that ADM has direct effects on
      expression of ANP in the cardiomyocyte by a mechanism that may involve the
      activation of adenylate cyclase, lending further support to the hypothesis that
      ADM may act in vivo as an important endocrine or paracrine modulator of
      cardiovascular function.

PMID- 9016774
TI  - Gene expressions of transferred human chromosome 8 in mouse cell lines.
AB  - Gene expressions were studied for the human chromosome 8 which were introduced by
      microcell fusion to three mouse tumor cell lines: A9, mouse melanoma B16F10 and
      SCVA2 derived from SV40-transformed scid fibroblasts. Nineteen genes in the human
      chromosome 8 were chosen, and the presence of their transcripts in these cells
      was examined by RT-PCR. The data showed that most of the human genes were
      expressed, with a few exceptions: the indoleamine 2, 3-dioxygenase gene was
      expressed in none of these cell lines, while two other genes, calbindin and
      neuronal nicotinic acetylcholine receptor subunit (Ach Rbeta3) genes, were not
      expressed in the A9 and SCVA2 cell lines, respectively, suggesting some cell- or
      species-specific transcriptional regulations exist. These results show that the
      mouse cell lines carrying a human chromosome are powerful tools for chromosome
      specific cDNA cloning.

PMID- 9016775
TI  - Elongation factor Tu1 of the antibiotic GE2270A producer Planobispora rosea has
      an unexpected resistance profile against EF-Tu targeted antibiotics.
AB  - Sensitivity of EF-Tu1 of the GE2270A producer Planobispora rosea towards GE2270A,
      pulvomycin and kirromycin was determined by band-shift assays for EF-Tu1
      antibiotic complex formation and by in vitro translation experiments. EF-Tu1 of
      P. rosea appeared to be not only totally resistant to GE2270A, but also ten times
      more resistant to kirromycin than EF-Tu1 of Streptomyces coelicolor. In contrast,
      P. rosea EF-Tu1 was found to be not resistant to pulvomycin, an antibiotic that
      just like GE2270A blocks EF-Tu x GTP x aminoacyl-tRNA complex formation. Previous
      in vivo and in vitro experiments with mixed populations of antibiotic resistant
      and sensitive EF-Tu species had shown that sensitivity to kirromycin and
      pulvomycin is dominant over resistance. In the case of GE2270A we observed,
      however, that sensitivity is recessive to resistance, which again points to a
      different action mechanism than in the case of pulvomycin. Besides the tuf1 gene
      encoding the regular elongation factor EF-Tu1 a gene similar to S. coelicolor
      tuf3 for a specialized EF-Tu was located in the P. rosea genome. The tuf1 gene
      was isolated and sequenced. The amino acid sequence of EF-Tul of P. rosea not
      only exhibits an unusual Tyr160 substitution (comparable to those described for
      kirromycin-resistant EF-Tus), but also shows significant changes of conserved
      amino acids in domain 2 that may be responsible for GE2270A resistance (the
      latter do not resemble those leading to pulvomycin resistance). P. rosea EF-Tu1
      thus is a first example of a bacterial EF-Tu with resistance against two
      divergently acting antibiotics.

PMID- 9016776
TI  - Alteration of free calcium levels and acylphosphatase muscular isoenzyme in
      cultured dystrophic skin fibroblasts.
AB  - Levels of free intracellular calcium have been measured on two cell lines of
      cultured human fibroblasts carrying the genetic lesions occurring in Duchenne and
      Becker dystrophies. Both cell lines elicited a markedly higher content of the
      cation (98 nM and 57 nM, respectively) than control fibroblasts (35 nM).
      Differences toward controls were statistically significant (p < 0.01). Dystrophic
      fibroblasts were also found to possess a significantly reduced amount by about
      50% of muscular acylphosphatase isoenzyme as compared to normal cells. As
      acylphosphatase was demonstrated to be involved in the regulation of Ca2+-ATPase
      activity from different sources, a hypothesis was formulated that could explain
      the disruption of calcium homeostasis as an effect of the altered acylphosphatase
      activity.

PMID- 9016777
TI  - QM is a novel zinc-binding transcription regulatory protein: its binding to c-Jun
      is regulated by zinc ions and phosphorylation by protein kinase C.
AB  - A novel method was developed for cloning of zinc-binding proteins. We used 65Zn2+
      as a probe to screen a human lung cDNA library, and isolated QM using this
      approach. QM appears to be a negative regulator of c-Jun that acts by binding to
      the leucine zipper region of c-Jun. We demonstrated that QM bound zinc ions and
      that such binding was necessary for the interaction of QM with c-Jun. We also
      showed that protein kinase C introduced about 1 mol of phosphate into 1 mol of
      QM. The binding of QM to c-Jun was decreased by 60% when QM had been
      phosphorylated. These results suggest that QM is a novel zinc-binding
      transcription regulatory protein and that interaction between QM and c-Jun is
      regulated by zinc ions and phosphorylation.

PMID- 9016778
TI  - Expression of members of a novel membrane linked metalloproteinase family (ADAM)
      in human articular chondrocytes.
AB  - Using resting chondrocytes derived from human articular femoral head and a
      conditionally immortalised human articular chondrocyte cell line we have studied
      the expression of members of the novel metalloproteinase/disintegrin family
      termed ADAM. Using RT-PCR we can detect the expression of ADAM-12 a novel family
      member isolated from myeloma cells [1]. We also find expression of ADAM 10 a
      functional metalloproteinase/disintegrin first isolated from bovine brain and
      ADAM-15 a metallodisintegrin isolated from mammary derived epithelial cells.
      Northern blotting was used to confirm expression. One main transcript is visible
      for ADAM-12 whereas both ADAM-10 and ADAM-15 have multiple transcripts indicating
      possible RNA variants potentially derived from alternative splicing or
      alternative use of polyadenylation sites. Since chondrocytes are proposed as an
      important source of metalloproteinase enzymes involved in joint pathology the
      potential relevance of the expression of these molecules to connective tissue
      disorders is discussed.

PMID- 9016779
TI  - Divergence of beta-myosin heavy chain (betaMHC) expression in fetal rat
      cardiomyocytes in vitro and adult rat heart in vivo.
AB  - The myosin heavy chain gene products are an important determinant of myocardial
      functional properties. Although a strong positive element (beta f1) within the
      betaMHC promoter region has previously been identified, to date no species
      comparisons in promoter strength have been made. To examine this question, we
      have used betaMHC deletion constructs, containing the rat or human beta f1
      enhancer region, to determine expression both in vitro using rat fetal
      cardiomyocytes and in vivo by direct injection into adult rat heart. When
      reporter constructs were transfected into cultured fetal rat cardiomyocytes, the
      human beta reporter was expressed more than 3 fold above the equivalent rat
      construct. Exchange of the beta f1 enhancer indicated that the human sequence of
      the beta f1 enhancer was largely responsible. However, these findings were not
      replicated when the reporters were injected into the adult rat heart. In the
      adult myocardium the levels of reporter expression were similar for the betaMHC
      promoter reporters studied. These findings demonstrate a divergence between
      primary cardiomyocytes maintained in culture and the cardiomyocytes found within
      the intact adult heart.

PMID- 9016780
TI  - Elevated plasma membrane and sarcoplasmic reticulum Ca2+ pump mRNA levels in
      cultured aortic smooth muscle cells from spontaneously hypertensive rats.
AB  - We have observed previously that Ca2+ pump-mediated Ca2+ efflux is elevated in
      cultured aortic smooth muscle cells from spontaneously hypertensive rats compared
      to those from Wistar-Kyoto rat controls. The objective of this work was to
      determine if these strains differ in mRNA levels for the PMCA1 isoform of the
      plasma membrane Ca2+-ATPase and the SERCA2 isoform of the sarcoplasmic reticulum
      Ca2+-ATPase. mRNA levels were compared in cultured aortic smooth muscle cells
      from 10-week-old male rats. PMCA1 and SERCA2 mRNA levels were elevated in SHR
      compared to WKY. Angiotensin II increased the level of PMCA1 and SERCA2 mRNA in
      both strains. These studies provide further evidence for altered Ca2+ homeostasis
      in hypertension at the level of Ca2+ transporting ATPases in the spontaneously
      hypertensive rat model. These data are also consistent with the hypothesis that
      the expression of these two Ca2+ pumps may be linked.

PMID- 9016782
TI  - Mammary protein synthesis is acutely regulated by the cellular hydration state.
AB  - The effect of cell-volume pertubations on mammary tissue protein synthesis has
      been examined. Cell-swelling, induced by a hyposmotic shock, increased the rate
      of incorporation of radiolabelled leucine and methionine into trichloroacetic
      acid precipitable material. The incorporation of radiolabel under both isosmotic
      and hyposmotic conditions was inhibited by cycloheximide. The increases in
      mammary protein synthesis as a result of cell-swelling may be attributable to an
      increase in casein synthesis. Conversely, cell-shrinking, as a consequence of a
      hyperosmotic challenge, almost abolished mammary protein (casein) synthesis. The
      finding that cell-volume pertubations had no significant effect on steady-state
      casein mRNA levels suggests that the regulation, within the time course of the
      experiments, is at the level of translation. The results strongly suggest that
      mammary cell volume may be an important cellular signal in the control of mammary
      protein synthesis in general and casein synthesis in particular.

PMID- 9016781
TI  - Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta
      tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast.
AB  - In this paper the chromosomal localization of the human skeletal muscle genes
      Troponin-I slow-twitch (TNNI1), Troponin-I fast-twitch (TNNI2), and Troponin-C
      fast (TNNC2) and the refinement of the position for alpha-Tropomyosin (TPM1) and
      beta-Tropomyosin (TPM2) are reported. By radiation hybrid mapping, TPM1 was
      assigned to chromosome 15q22.1, TPM2 to chromosome 9p13.2-p13.1, TNNI1 to
      chromosome 1q31.3, TNNI2 to chromosome 11p15.5, and TNNC2 to chromosome 20q12
      q13.11. The genomic distribution of these genes is discussed, with particular
      emphasis on the cluster organization of the Troponin genes.

PMID- 9016783
TI  - Up-regulation of rho A and rho-kinase mRNAs in the rat myometrium during
      pregnancy.
AB  - It has recently been suggested that rho A and rho kinase (ROK) play a role in the
      increase in the Ca2+ sensitivity of the smooth muscle myofilaments. In the
      present study, we investigated the mRNA expressions of rho A and two types of ROK
      (alpha and beta) in the myometrium obtained from both non-pregnant and pregnant
      rats. Reverse transcription polymerase chain reaction (RT-PCR) experiments using
      total RNA from these tissue specimens and the specific primers revealed rho A and
      both types of ROK mRNAs to be expressed in the rat myometrium. The mRNA
      expressions of rho A, ROK alpha and ROK beta in the pregnant myometrium were
      found to increase in comparison to those in the non-pregnant myometrium. These
      results thus support the idea that the up-regulation of these proteins might be
      involved in the mechanism underlying the increased contractility of the pregnant
      myometrium.

PMID- 9016784
TI  - ob gene expression and secretion of leptin following differentiation of rat
      preadipocytes to adipocytes in primary culture.
AB  - Expression of the ob gene and production of leptin have been examined on
      differentiation of rat fibroblastic preadipocytes to adipocytes in primary
      culture. Preadipocytes were obtained from the inguinal fat pad of suckling rats,
      and following differentiation the cells contained lipid droplets and the mRNAs
      for both lipoprotein lipase and adipsin were detected by Northern blotting. ob
      mRNA was not, however, detected on Northern blots, but analysis by RT-PCR
      indicated that the ob gene was expressed, particularly after differentiation.
      Measurement of leptin in the culture medium by ELISA showed that the ob gene
      product was secreted by adipocytes from approximately 4 days after the induction
      of differentiation. Leptin production was sustained over a 2-week period with a
      peak at 8-10 days post-induction. Dexamethasone stimulated leptin production,
      while an inhibition was observed with the beta-adrenoceptor agonist isoprenaline.
      These results demonstrate that following the differentiation of fibroblastic
      preadipocytes to adipocytes in primary culture, leptin is secreted with the cells
      responding to stimuli which regulate production of the hormone.

PMID- 9016785
TI  - Transforming growth factor beta increases the activity of phosphatidate
      phosphohydrolase-1 in rat hepatocytes.
AB  - Phosphatidic acid (PA) is a potent second messenger arising from growth factor
      induced stimulation of phospholipase D which hydrolyses phosphatidylcholine. PA
      is hydrolysed to diacylglycerol by PA phosphohydrolase (PAP) which exists in two
      forms: PAP-1 and PAP-2. In rat hepatocyte cultures, overnight (20h) incubation
      with transforming growth factor (TGF) beta (1 ng/ml) increased PAP-1 activity two
      fold. This effect was concentration and time dependent and was greatest at low
      cell density. The TGFbeta effect on PAP-1 was additive to stimulation induced by
      dexamethasone but not by glucagon and it reversed the inhibition by insulin.
      Epidermal growth factor had no effect on PAP-1 activity. None of the above
      hormones or growth factors affected the subcellular distribution of PAP-1.
      Stimulation of PAP-1 by TGFbeta may be involved in mediating some of its
      biological effects.

PMID- 9016786
TI  - The nucleolar phosphoprotein P130 is a GTPase/ATPase with intrinsic property to
      form large complexes triggered by F- and Mg2+.
AB  - We have previously identified a human nucleolar phosphoprotein p130 whose
      alterations during mitosis are correlated well with the nucleolar disassembly and
      reassembly. Further studies found that p130 in the cell lysates or after being
      purified by immunoprecipitation was able to form large complexes triggered by F-
      and Mg2+. These sodium dodecyl sulfate-insoluble p130 molecules were readily
      dissociated by adding EDTA to the complexes. It is known that F- and Mg2+ act on
      many GTPases and ATPases through the induction of a conformational transition
      mimicking the nucleoside triphosphate-bound state. These initial observations led
      us to discover that p130 functions as a GTP/ATP binding protein with intrinsic
      GTPase/ATPase activities. The rate of GTP hydrolysis by purified p130 under our
      experimental conditions was 0.8 mol/min/mol of p130. These results imply that
      p130, a novel nucleolar GTPase/ATPase, may switch its conformation in a
      nucleotide-dependent manner.

PMID- 9016787
TI  - Comparison of three nonviral transfection methods for foreign gene expression in
      early chicken embryos in ovo.
AB  - By using three nonviral transfection methods, i.e., microparticle bombardment,
      lipofection and electroporation, the transfection efficiency and the expression
      intensity of a lacZ reporter gene were compared in developing chicken embryos in
      ovo. Of the three transfection methods employed, electroporation conferred the
      strongest expression of the bacterial lacZ gene with similar transfection
      efficiency. The results suggest that as far as transient gene expression is
      concerned, electroporation would provide a useful and efficient nonviral means of
      foreign gene transfection to somatic cells of living chicken embryos in ovo.

PMID- 9016788
TI  - Cloning and functional expression in yeast of a cDNA coding for an obtusifoliol
      14alpha-demethylase (CYP51) in wheat.
AB  - Screening of a wheat cDNA library with an heterologous CYP81B1 probe from
      Helianthus tuberosus led to the isolation of a partial cDNA coding a protein with
      all the characteristics of a typical P450 with high homology (32-39% identity) to
      the fungal and mammalian CYP51s. Extensive screening of several wheat cDNA
      libraries isolated a longer cDNA (W516) coding a peptide of 453 amino acids.
      Alignment of W516 with other P450 sequences revealed that it was missing a
      segment corresponding to the N-terminal membrane anchor of the protein. The
      corresponding segment from the yeast lanosterol 14alpha-demethylase was linked to
      the partial wheat cDNA and the chimera expressed in Saccharomyces cerevisiae.
      Compared to microsomes from control yeasts, membranes of yeast expressing the
      chimera catalysed 14alpha-demethylation of obtusifoliol with an increased
      efficiency relative to lanosterol demethylase activity. W516 is thus a plant
      member of the most ancient and conserved P450 family, CYP51.

PMID- 9016789
TI  - Rapamycin potentiates dexamethasone-induced apoptosis and inhibits JNK activity
      in lymphoblastoid cells.
AB  - The immunosuppressant rapamycin (RAP) potentiated apoptosis of the murine T
      lymphoblastoid cell line S49 induced by dexamethasone (DEX), while RAP by itself
      did not induce apoptosis of the cells. FK506, in contrast, had no effect on DEX
      induced apoptosis; moreover, an excess of FK506 reversed the potentiation of
      apoptosis by RAP, indicating that RAP exerts its effects through binding to FKBP.
      Both RAP and FK506 enhanced the MMTV promoter activity by dexamethasone,
      suggesting that the potentiation of apoptosis is not likely explained by the
      selective enhancement of transcriptional activity of the glucocorticoid receptor.
      Of interest, the basal activity of c-Jun kinase (JNK), whose activation has been
      recently suggested to be involved in cell survival signals in lymphocytes, was
      reduced by RAP in S49 cells. The reduction of JNK activity by RAP was reversed by
      the addition of an excess of FK506. In summary, we demonstrate for the first time
      that RAP has the ability to inhibit JNK activity in lymphocytes where the drug
      enhances apoptosis.

PMID- 9016790
TI  - Identification of binding domains for basic fibroblast growth factor in
      proteoglycan macrophage colony-stimulating factor.
AB  - We recently demonstrated that proteoglycan macrophage colony-stimulating factor
      (PG-M-CSF) binds basic fibroblast growth factor (bFGF) and neutralizes the
      biological activity of bFGF. In this study, we identified the binding sites of PG
      M-CSF for bFGF. We examined the binding of bFGF to overlapping 12-mer peptides
      with the sequence of the putative binding region. High affinity binding was
      detected at two peaks; one consisted of the three adjacent peptides, 212-223, 213
      224 and 214-225 and the other, of the three adjacent peptides, 246-257, 247-258
      and 248-259. The synthetic peptide (212VDPGSAKQRPPRST225) did not inhibit bFGF
      binding to another peptide (246PQPRPSVGAFNPGM259), and vice versa. However, both
      peptides inhibited the bFGF-induced but not platelet-derived growth factor
      induced stimulation of DNA synthesis in murine Balb/c 3T3 cells.

PMID- 9016791
TI  - Functional modulation of ATPase of P-glycoprotein by C219, a monoclonal antibody
      against P-glycoprotein.
AB  - P-glycoprotein functions as an ATP-driven efflux pump for antitumor agents. C219
      is a monoclonal antibody which recognizes regions near both ATP binding domains
      in each half of P-glycoprotein. In this study, we have demonstrated that C219
      inhibits the ATPase activity of P-glycoprotein based on the following findings:
      1) the inhibition of total ATPase activity by C219 was selective to P
      glycoprotein-positive membranes; 2) the C219-sensitive fraction of ATPase
      correlated the expression of P-glycoprotein; and 3) modulators of P-glycoprotein
      ATPase, verapamil and cyclosporin A, affected the C219-sensitive fraction of
      ATPase. The photolabeling of P-glycoprotein with 8-azido-[alpha-32P]ATP was
      inhibited by C219, suggesting that the inhibition of ATP binding by C219 reduced
      the activity. Since C219 interacts with P-glycoprotein ATPase, C219 might become
      a useful tool for studying the role of P-glycoprotein ATPase.

PMID- 9016792
TI  - Isolation of a new peroxisome-deficient CHO cell mutant defective in peroxisome
      targeting signal-1 receptor.
AB  - For the study of mechanism of peroxisome biogenesis, we attempted to isolate CHO
      cell mutants deficient in peroxisome biogenesis. We used as the parent strain a
      stable CHO transformant of rat PEX2 (formerly named peroxisome assembly factor-1)
      cDNA, to avoid unusually frequent isolation of Pex2 mutants. Among the three
      peroxisome-deficient mutants obtained, ZP102 was a new CHO mutant of
      complementation group 2, and was restored for peroxisome assembly by the
      transfection of human PEX5 (formerly called PXR1 or PTS1R) cDNA. This approach
      would facilitate the isolation of new complementation gorups of peroxisome
      deficient CHO mutants and the identification of essential genes for peroxisome
      biogenesis.

PMID- 9016793
TI  - Transcriptional regulation by competition between ELP isoforms and nuclear
      receptors.
AB  - ELP is a transcription factor belonging to the nuclear receptor superfamily. The
      consensus binding sequence for ELP contains a half site of the nuclear receptor
      recognition element. We demonstrated previously that ELP1, the repressor type
      isoform of ELP, competes for binding with the retinoic acid receptor and
      represses retinoic acid-induced transactivation. In this study, competitive
      repression by ELP1 was investigated for several other nuclear receptors. As in
      the case of the retinoic acid receptor, binding of vitamin D receptor, thyroid
      hormone receptor, and estrogen receptor could be competed by ELP1, resulting in
      repression of their ligand-dependent transactivation. Interestingly, the
      activator-type ELP isoforms were capable of repressing retinoic acid-induced
      transactivation through binding to the retinoic acid receptor binding element.
      These data suggest that competition for target DNA binding is a general mechanism
      of transcriptional repression by ELP isoforms.

PMID- 9016794
TI  - Analysis of the promoter region of the human VEGF-related factor gene.
AB  - We have characterised the promoters of the human and murine VRF (vascular
      endothelial growth factor (VEGF) related factor) gene. A series of deletions were
      made of a 553-bp region 5' of the VRF initiation codon and were used in a
      luciferase reporter gene assay to determine the minimal promoter of the VRF gene.
      The region between base pairs -443 and -195 was sufficient to mediate
      transcription in lymphocytes and the region between -550 and -443 enhanced this
      promoter activity. Primer extension studies identified two regions of
      transcription initiation, both of which are preceded by Sp1, AP-2 and Egr-1
      transcription factor binding sites. The VRF promoter is similar to VEGF in that
      it is associated with a CpG island, contains sites for Sp1 and AP-2, and lacks a
      TATA box. However, it has marked differences in that the promoter contains Egr-1
      sites and lacks both hypoxia-inducible factor-1 and AP-1 sites. These data may
      indicate that expression of these two growth factors is regulated by different
      physiological stimuli.

PMID- 9016795
TI  - Characterization of rat receptor-like protein tyrosine phosphatase gamma
      isoforms.
AB  - We identified four isoforms of receptor-like protein tyrosine phosphatase gamma
      (RPTPgamma) from rat brain by cDNA cloning. We designated these molecules
      RPTPgamma-A, -B, -C, and -S. RPTPgamma-A was the longest form and had the same
      structure as human and mouse RPTPgamma. RPTPgamma-B lacked the intracellular
      juxtamembrane 29 amino acids of RPTPgamma-A. RPTPgamma-C had a single phosphatase
      domain. RPTPgamma-S is an extracellular variant of RPTPgamma. mRNAs of the four
      isoforms were expressed in the brain, kidney, lung, and heart. Transfection of
      RPTPgamma-A and -S expression plasmids into COS7 cells resulted in the expression
      of membrane-bound 190-kDa proteins and secreted 120-kDa proteins, respectively.
      These molecules were similar to PTPzeta/RPTPbeta with regard not only to
      structure but also to the presence of both secretory and transmembrane forms.
      However, RPTPgamma isoforms were not expressed as proteoglycans.

PMID- 9016796
TI  - Adenovirus-mediated inducible gene expression through tetracycline-controllable
      transactivator with nuclear localization signal.
AB  - Tetracycline-controllable expression vectors are widely used for inducible
      expression in mammalian cells. The limitation of this system is the difficulty in
      expressing high levels of the chimeric transactivator tTA. In this study, we
      demonstrate a utility of recombinant adenoviruses for the tetracycline
      controllable expression system. Unexpectedly, the original tTA transactivator did
      not show sufficient regulation of the reporter gene expression driven by the
      tetracycline-responsive promoter (Tet). By adding the nuclear localization signal
      on the tTA transactivator (NtTA), we achieved tight regulation and high-level
      induction of the reporter gene expression. The NtTA driven by various promoters
      demonstrated strict tetracycline controllability at 1 microg/ml of tetracycline
      and above. The methodology for adenovirus-mediated inducible gene expression has
      wide applicability. Controllable expression of cytotoxic viral proteins will be
      applicable for antiviral vaccine productions and pseudotype viral vector
      generations.

PMID- 9016797
TI  - Wild-type, but not mutant-type, p53 enhances nuclear accumulation of the NS3
      protein of hepatitis C virus.
AB  - By using vaccinia virus-T7 hybrid expression system, subcellular localization of
      the NS3 protein of hepatitis C virus was studied. Full-size NS3 (NS3F) and a
      carboxy-terminally truncated form (NS3 deltaC) were localized in the cytoplasm
      and the nucleus when expressed alone. However, NS3F and NS3 deltaC, but not amino
      and carboxy-terminally truncated form (NS3 deltaN deltaC), were each co
      localized with wild-type p53 almost exclusively in the nucleus upon co
      expression. The wild-type p53-induced nuclear accumulation of NS3F was inhibited
      only partially by NS4A. When co-expressed with mutant-type p53, NS3F and NS3
      deltaC were each co-localized with it exclusively in the cytoplasm. Taken
      together, the present results suggest that wild-type p53 enhances nuclear
      accumulation of NS3F and NS3 deltaC through the involvement of their amino
      terminal sequences even in the presence of NS4A, and that mutant-type p53
      inhibits their nuclear, and enhances their cytoplasmic, accumulation.

PMID- 9016798
TI  - Serotonin activates electrolyte transport via 5-HT2A receptor in rat colonic
      crypt cells.
AB  - The aim of this study was to demonstrate that 5-HT activates electrolyte
      transport directly via 5-HT2A receptor in rat colonic crypt cells. Patch-clamp
      whole cell recording was performed in isolated crypts to measure the 5-HT-induced
      changes in electrogenic K+ and Cl- currents. Superfusing 5-HT (10 microM) in the
      bath solution increased both K+ and Cl- currents, which were antagonized by the
      presence of ketanserin (1 microM), a selective 5-HT2A antagonist, in the bath
      solution. Mesulergine (1 microM) a 5-HT2A and 5-HT2C antagonist, had no
      inhibitory effect. Strong chelation of the intracellular Ca2+ by 5 mM BAPTA
      inhibited 5-HT-induced currents. 5-HT also failed to activate K+ and C1- currents
      in the presence of GDPbetaS (0.5 mM) in the pipette solution. Intracellular
      administration of GTPgammaS (0.1 mM) mimicked the stimulatory effect of 5-HT,
      that was inhibited by 5 mM BAPTA. H-7 (0.05 mM), an inhibitor of protein kinase
      C, A, and G, did not affect the currents. These data indicate that a G protein
      coupled pathway is involved in the activation of electrolyte secretion via 5-HT2A
      receptor.

PMID- 9016799
TI  - Domain organization of murine mdr1b P-glycoprotein: the cytoplasmic linker region
      is a potential dimerization domain.
AB  - P-glycoprotein is an integral membrane protein that functions as a cytotoxic drug
      efflux pump. Studies suggest that the transporter exists in the membrane as a
      dimer and possibly higher order structures. We report the bacterial expression of
      the linker region (amino acids 621-688) of murine mdr1b P-glycoprotein and
      demonstrate that this region, which serves to link the two homologous halves of
      the transporter, has the potential to serve as a dimerization domain. The
      recombinant peptide (8742 daltons) eluted from a gel filtration column at a
      position corresponding to a dimer (i.e. 17,500 daltons). A dimer:monomer
      equilibrium, as a function of peptide concentration, was confirmed by large zone
      gel filtration chromatography. The dissociation constant (KD) for the
      dimer:monomer equilibrium was 350 nM. It was possible to dissociate the dimer by
      low pH (3.0) or high ionic strength (2.5 M NaCl). Dimerization was not affected
      by an alkaline pH of 10 or 5 mM EDTA. Studies with a truncated linker peptide
      indicated that the N-terminal 48 amino acids were sufficient for dimerization.

PMID- 9016800
TI  - The stress-activated c-Jun protein kinase (JNK) is stimulated by lipoxygenase
      pathway product 12-HETE in RIN m5F cells.
AB  - Cytokine induced pancreatic beta-cell destruction seen in Type 1 diabetes and
      islet graft rejection involves multiple intracellular signaling pathways that
      directly or indirectly lead to inflammatory damage or programmed cell death. IL
      1beta has been shown to stimulate the 12-lipoxygenase pathway product 12-HETE, in
      RIN m5F cells; however, the precise role of 12-LO activation in mediating
      cytokine effects is not clear. Since the stress-activated protein kinase, JNK,
      has been linked to cytokine mediated inflammatory actions, we studied the effect
      of two LO products, 12-HETE and 15-HETE, on JNK activity. We demonstrate that 1
      nM 12-HETE stimulates JNK activity, while 1 nM 15-HETE, the 15-lipoxygenase
      pathway product, does not. These results suggest 12-HETE is a novel upstream
      signal for IL-1beta induced JNK activation in RIN m5F cells.

PMID- 9016801
TI  - Sturgeon proopiomelanocortin has a remnant of gamma-melanotropin.
AB  - For the investigation of the evolution of the proopiomelanocortin (POMC) gene in
      early ray-finned fishes, nucleotide sequence of POMC cDNA from a chondrostean
      fish, the sturgeon has been determined. POMC cDNA was amplified by PCR from
      double-strand cDNA prepared from sturgeon pituitary and ligated with lambdaZAP
      II. The POMC cDNA consists of 1079 bp without a poly-A. An open reading frame of
      the POMC cDNA encodes 263 amino acid residues. Sturgeon POMC contains ACTH, alpha
      melanotropin (MSH), beta-MSH and beta-END at positions (115-153), (115-127), (186
      202) and (205-238), respectively. Location of POMC(51-72) is homologous to gamma
      MSH, whereas the third residue of MSH-core sequence, His-Phe-Arg-Trp, is changed
      to His. Moreover, there are no basic amino acids to serve as a processing signal
      on the N-terminal side of POMC(51-72). These structural characteristics suggest
      that an ancestor of the ray-finned fishes had gamma-MSH, whereas significant
      mutations occurred during the evolution of chondrostean fish.

PMID- 9016802
TI  - An AP1 element is involved in transcriptional regulation of delta9-desaturase
      gene of Histoplasma capsulatum.
AB  - We have characterized a region of the promoter of a cloned delta9-desaturase gene
      (Ole1) of Histoplasma capsulatum, a dimorphic pathogenic fungus of humans. The
      product of the delta9-desaturase gene is involved in regulating membrane fluid
      state in animal cells and microorganisms. To identify sequences critical for Ole1
      expression in both the saprobic mycelial and parasitic yeast phases of this
      organism, we performed a deletion analysis. Evidence is presented that a 240 nt
      region of the proximal promoter is involved in a phase-specific binding in vitro.
      By sequence analysis we have identified one likely regulatory element that
      coincides with an AP1 binding site (TGACTAA) that is located at -740 nt of 5'
      upstream from the ATG. Using gel mobility shift assays, we show that this cis
      acting element binds nuclear proteins extracted from the yeast and mycelial
      phases of H. capsulatum that may participate in control of expression of the
      delta9-desaturase gene.

PMID- 9016803
TI  - Biochemical evidence for orphanin FQ/nociceptin receptor heterogeneity in mouse
      brain.
AB  - A recently identified novel peptide, orphanin FQ/nociceptin (OFQ/N), is an
      endogenous ligand for a unique member of the cloned opioid receptor family.
      Saturation studies in mouse brain membranes reveal curvilinear Scatchard plots
      with both a higher (KD 3.8 pM, Bmax 31.6 fmol/mg protein) and a lower (KD 896 pM,
      Bmax 233 fmol/mg protein) affinity site in brain tissue, compared to only a
      single site in transfected CHO cells (KD 36 pM). Competition studies confirm the
      high affinity of OFQ/N for this site, but shallow Hill slopes suggest
      heterogeneity. Traditional opioids have poor affinity for this receptor and OFQ/N
      and its fragments do not label traditional opioid receptors. In brain
      homogenates, both OFQ/N and OFQ/N(1-11) inhibit forskolin-stimulated camp
      accumulation with IC50 values of 1 nM or less, an action which is readily
      reversed by opioid antagonists. OFQ/N(1-7) shows little activity. Together, these
      studies suggest the presence of heterogeneous, functionally active OFQ/N
      receptors in mouse brain.

PMID- 9016804
TI  - Laminin reduces HSV-1 spread from cell to cell in human keratinocyte cultures.
AB  - Herpes simplex virus-1 (HSV-1) infects epidermal cells where it replicates and
      spreads from cell to cell. While some of the viral factors responsible for cell
      to-cell spread are known, the host cell molecules and structures which are
      utilized by HSV-1 during spread are not well studied. Here we report that a
      laminin substrate reduced the ability of HSV-1 to spread from cell to cell in
      cultures of a human keratinocyte cell line (HaCaT). Laminin did not reduce spread
      of the virus by decreasing the viral replication rate. However, laminin did
      stimulate the formation of tight junctions between HaCaT cells, suggesting that
      tight junctions can affect cell-to-cell spread of HSV-1. Since laminin is an
      abundant component of the basement membrane in vivo, culturing cells on laminin
      may provide an assay which more accurately reflects the rate and mechanism of HSV
      1 cell-to-cell spread in vivo.

PMID- 9016805
TI  - CFTR-like chloride channels in non-ciliated bronchiolar epithelial (Clara) cells.
AB  - Distal airways are believed to be a major site of disease in cystic fibrosis. The
      product of the CF gene, CFTR, is expressed in non-ciliated bronchiolar epithelial
      (Clara) cells. Clara cells in primary culture are capable of Cl- secretion which
      can be stimulated by cAMP and extracellular nucleotides. We used the patch clamp
      technique to look for Cl- channels in the apical membrane of rabbit Clara cells.
      In cell-attached patches, we recorded Cl- channels with a conductance for outward
      currents of 7.5 +/- 0.4 pS (n = 10) and for inward currents of 3.2 +/- 0.5 pS (n
      = 10); these channels typically exhibited slow kinetics and were not inhibited by
      the Cl- channel blockers NPPB and DIDS. Channel activity was not noticeably
      dependent on pipette potential. Addition of chlorophenylthio-cyclic AMP (cpt
      cAMP) to the bath increased the percentage of cell-attached patches with active
      channels (33.8% vs 56.7%; p< 0.05) and the channel open probability (0.49 +/-
      0.03 vs 0.84 +/- 0.02; p< 0.05). Extracellular ATP increased the percentage of
      cell-attached patches with active channels (28.7% to 50.0%; p< 0.05) but had no
      significant effect on the channel open probability (0.62 +/- 0.07 vs 0.60 +/-
      0.06). In conclusion, rabbit non-ciliated bronchiolar epithelial cells express
      low-conductance Cl- channels that share many similarities with the CFTR-related
      Cl- channel and are regulated by cAMP and extracellular ATP.

PMID- 9016806
TI  - Peroxynitrite induces the conversion of xanthine dehydrogenase to oxidase in
      rabbit liver.
AB  - Effect of peroxynitrite (ONOO-) on the conversion of xanthine dehydrogenase to
      oxidase in rabbit liver was examined. ONOO- (25-200 microM) induced the
      conversion of xanthine dehydrogenase to oxidase in a dose-dependent manner. The
      addition of hydroxyl radical scavengers (mannitol and dimethyl sulfoxide) gave no
      alteration in the ONOO(-)-induced conversion of xanthine dehydrogenase to
      oxidase, implying that the action of ONOO- is not due to hydroxyl radicals which
      may be formed from ONOO-. The experiment utilizing dithiothreitol also revealed
      that the action of ONOO- might be due to oxidation of sulfhydryl group of
      xanthine dehydrogenase. These results suggest that ONOO- has the potential to
      convert xanthine dehydrogenase to oxidase, and that this effect may be correlated
      with cytotoxic actions of ONOO-.

PMID- 9016807
TI  - Phosphorylation of growth factor receptor binding protein-2 by pp60c-src tyrosine
      kinase.
AB  - Growth factor receptor binding protein-2 (GRB2) couples growth factor receptor
      activation to the p21-ras nucleotide exchange factor son-of-sevenless. Both GRB2
      and son-of-sevenless display phosphorylation in cells treated with growth factors
      and may be subject to feed back regulation in mitogen-stimulated cells. Herein,
      we demonstrate that pp60c-src can utilize GRB2 as a substrate. NIH 3T3
      fibroblasts overexpressing pp60v-src contained high levels of phosphorylated
      GRB2. In comparison, control fibroblasts contained phosphorylated GRB2 only after
      stimulation with platelet-derived growth factor. Analysis of GRB2 immune
      complexes isolated from fibroblasts stimulated with PDGF or transformed by pp60v
      src revealed a kinase activity capable of phosphorylating GRB2 in vitro.
      Incubation of native or recombinant GRB2 with purified pp60c-src provided
      additional support for pp60c-src as the kinase for GRB2. Deletion mutants of GRB2
      demonstrated that pp60c-src phosphorylated GRB2 on a tyrosine residue (residue
      160) located between the SH2 domain and carboxyl terminal SH3 domain. Mutation of
      tyrosine 160 to phenylalanine abolished phosphorylation of GRB2 by pp60c-src. We
      conclude that Src finds GRB2 a suitable substrate in vitro and may phosphorylate
      GRB2 in cells responding to platelet-derived growth factor.

PMID- 9016808
TI  - Mitogenic and metabolic actions of epidermal growth factor on rat articular
      chondrocytes: modulation by fetal calf serum, transforming growth factor-beta,
      and tyrphostin.
AB  - The effects of human recombinant epidermal growth factor (EGF) on rat articular
      chondrocytes from humeral and femoral head cartilage of 21-day-old Wistar rats
      were analyzed. The cells were cultured under standard conditions as monolayers.
      Cell proliferation was studied by [3H]thymidine incorporation and determination
      of DNA content, proteoglycan synthesis by [35S]sulfate incorporation, and
      collagen synthesis by [3H]proline incorporation. The presence of specific
      receptors was confirmed by [125I]-EGF binding and that of EGF and EGF-receptor
      (EGF-R) mRNA by reverse transcription and the polymerase chain reaction. EGF (0.5
      2.5 ng/ml) stimulated [3H]thymidine incorporation and increased DNA content of
      cultures. The effect was strongest when serum concentration was low (< or =1%)
      and was lost at high (> or =7.5%) serum concentrations. The EGF-induced effect on
      deoxynucleic acid synthesis was inhibited by transforming growth factor-beta and
      tyrphostin, a tyrosine kinase inhibitor that blocks the phosphorylation of
      tyrosine residues on EGF-R. Cultured rat articular chondrocytes possess a single
      class of high-affinity binding sites (Kd 0.18 nM). There were about 4.5 x 10(9)
      binding sites per microgram of DNA or about 37,800 binding sites per cell with
      8.3 pg DNA per cell. Cultured cells contained EGF mRNA and EGF-R mRNA. Incubation
      of cells with EGF for 24 h decreased the EGF mRNA transcripts and increased the
      EGF-R mRNA levels. These findings suggest that EGF probably takes part in the
      regulation of chondrocyte activity under normal and presumably pathological
      conditions.

PMID- 9016809
TI  - Triiodothyronine stimulates and glucagon inhibits transcription of the acetyl-CoA
      carboxylase gene in chick embryo hepatocytes: glucose and insulin amplify the
      effect of triiodothyronine.
AB  - The mechanisms by which triiodothyronine (T3), glucose, insulin, and glucagon
      regulate acetyl-CoA carboxylase expression in primary cultures of chick embryo
      hepatocytes have been investigated. Incubating hepatocytes with T3 in the absence
      of glucose caused a fourfold increase in acetyl-CoA carboxylase activity.
      Addition of glucose (20 mM) enhanced the T3-induced increase in acetyl-CoA
      carboxylase activity by threefold but had no effect on enzyme activity in the
      absence of T3. The effects of T3 and glucose on acetyl-CoA carboxylase activity
      were accompanied by similar changes in acetyl-CoA carboxylase mRNA levels,
      indicating that regulation occurred at a pretranslational step. Xylitol mimicked
      the effect of glucose on acetyl-CoA carboxylase mRNA abundance, suggesting that
      an intermediate(s) of the nonoxidative branch of the pentose phosphate pathway
      may be involved in mediating this response. Insulin accelerated the accumulation
      of acetyl-CoA carboxylase mRNA abundance caused by T3 and glucose but had no
      effect on steady-state levels of acetyl-CoA carboxylase mRNA in the absence or
      presence of T3. Glucagon caused a 65% decrease in the accumulation of acetyl-CoA
      carboxylase mRNA in hepatocytes incubated with T3 and glucose. The effects of T3,
      glucose, insulin, and glucagon on the abundance of acetyl-CoA carboxylase mRNA
      were accounted for by changes in the transcription rate of the acetyl-CoA
      carboxylase gene. These data support the hypothesis that T3, glucose, insulin,
      and glucagon play a role in mediating the effects of nutritional manipulation on
      transcription of acetyl-CoA carboxylase in liver.

PMID- 9016810
TI  - Control of hepatic fatty acid oxidation by 5'-AMP-activated protein kinase
      involves a malonyl-CoA-dependent and a malonyl-CoA-independent mechanism.
AB  - Incubation of rat hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside
      (AICAR), an activator of the 5'-AMP-activated protein kinase (AMPK), produced a
      twofold stimulation of palmitate oxidation and of the activity of carnitine
      palmitoyltransferase I (CPT-I), together with a profound decrease of the activity
      of acetyl-CoA carboxylase and of the intracellular level of malonyl-CoA. AICAR
      induced CPT-I stimulation progressively blunted with time after cell
      permeabilization, pointing to reversal of conformational constraints of the
      enzyme in control cells due to the permeabilization-triggered dilution of
      intracellular malonyl-CoA. The stimulation stabilized at a steady 20-25%. This 20
      25% increase in CPT-I activity survived upon complete removal of malonyl-CoA from
      the permeabilized cells, indicating that it was not dependent on the malonyl-CoA
      concentration of the cell. This malonyl-CoA-independent activation of CPT-I was
      not evident when mitochondria were isolated for assay of enzyme activity or when
      cells were disrupted by vigorous sonication. In addition, the microtubule
      stabilizer taxol prevented the malonyl-CoA-independent stimulation of CPT-I
      induced by AICAR. Hence, stimulation of hepatic fatty acid oxidation by AMPK
      seems to rely on the activation of CPT-I by two different mechanisms:
      deinhibition of CPT-I induced by depletion of intracellular malonyl-CoA levels
      and malonyl-CoA-independent stimulation of CPT-I, which might involve modulation
      of interactions between CPT-I and cytoskeletal components.

PMID- 9016811
TI  - Oxidation of butadiene monoxide to meso- and (+/-)-diepoxybutane by cDNA
      expressed human cytochrome P450s and by mouse, rat, and human liver microsomes:
      evidence for preferential hydration of meso-diepoxybutane in rat and human liver
      microsomes.
AB  - Butadiene monoxide (BM) can be oxidized by cDNA-expressed human cytochrome P450
      enzymes and by mouse, rat, and human liver microsomes to yield meso- and (+/-)
      diepoxybutane (DEB). The DEB diastereomers were separated by gas chromatography
      (GC) and characterized by GC-mass spectrometry. Of eight cDNA-expressed human
      P450 enzymes examined, only incubations with 2E1, 2A6, and 2C9 led to DEB
      detection; total DEB formation rate by 2E1 was nearly four- and sixfold higher
      than the rates observed with 2C9 and 2A6, respectively, while incubations with
      1A1, 1A2, 2B6, 2D6, or 3A4 did not lead to DEB detection. meso-DEB was detected
      preferentially in 2A6 and 2E1 incubations (ratios nearly 2:1), whereas
      incubations with 2C9 led to detection of both isomers in approximately equal
      amounts. Incubations of mouse, rat, or human liver microsomes with BM and
      chlorzoxazone provided further evidence for the involvement of 2E1 in BM
      oxidation; meso-DEB was the major DEB form detected at high BM concentrations.
      The Vmax/Km ratio for total DEB formation obtained with mouse liver microsomes
      was higher than the ratios obtained with rat and human liver microsomes. However,
      DEB hydrolysis in human liver microsomes was greater than that observed with rat
      liver microsomes, while no hydrolysis was detectable in mouse liver microsomes.
      When the DEB diastereomers were added in a 1:1 ratio to human or rat liver
      microsomes, selective hydrolysis of meso-DEB was observed. These results, which
      characterize new metabolic reactions for BM and DEB, may be of toxicological
      importance, as significant species differences reflecting both the
      stereoselective oxidation of BM by P450 enzymes and the subsequent preferential
      meso-DEB hydration by epoxide hydrolase have been demonstrated.

PMID- 9016812
TI  - Taxol production and taxadiene synthase activity in Taxus canadensis cell
      suspension cultures.
AB  - The cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene
      represents the first committed, and a slow, step in the complex biosynthetic
      pathway leading to the anticancer drug Taxol. The cyclization enzyme, taxadiene
      synthase, has been previously purified from Pacific yew (Taxus brevifolia) stem
      and characterized, and the corresponding cDNA has been isolated. To better assess
      the role of taxadiene synthase in the control of pathway flux in Canadian yew (T.
      canadensis) cells, a reliable system for production of Taxol in suspension
      culture, the enzyme from this source was isolated and shown to be
      chromatographically, electrophoretically, and kinetically identical to that of T.
      brevifolia stem. Results from the analysis of enzyme activity levels during the
      time course of Taxol accumulation in developing cell cultures of T. canadensis
      indicate that rate-limiting transformations lay farther down the pathway than the
      cyclization step in this system.

PMID- 9016813
TI  - Comparison of Limulus alpha-macroglobulin with human alpha2-macroglobulin: thiol
      ester characterization, subunit organization, and conformational change.
AB  - The properties of the thiol ester-containing alpha-macroglobulin (alphaM) from
      the horseshoe crab (Limulus polyphemus) have been compared with those of the
      human analogue (alpha2M). Thiol ester accessibility was more restricted in
      Limulus alphaM than in human alpha2M. Fluorescent probes attached to the thiol
      ester cysteine indicated very similar local environments in the cleaved state of
      the two alphaMs. The separation between the two thiol ester cysteines in the
      cleaved state, determined by fluorescence resonance energy transfer, was also
      very similar for the two alphaMs. Differences were found in the oligomerization
      state and conformational changes of the two proteins. Whereas human alpha2M
      appears to be exclusively a dimer of dimers, Limulus alphaM can exist in both
      tetrameric and dimeric forms, although with marked preference for the dimer.
      Conformational change within a dimeric trapping unit, monitored by 6-(p
      toluidino)-2-napthalene-sulfonic acid fluorescence change, showed that each
      monomer of the Limulus alphaM dimer appears to change conformation independently,
      whereas human alpha2M requires both thiol esters within a functional unit to be
      cleaved before the conformational change occurs. Taken together, these findings
      indicate that, whereas individual thiol esters in both types of alphaM are
      similar in properties, differences in subunit-subunit interaction result both in
      differences in state of oligomerization and in cooperativity of conformational
      change, which may reflect a fundamentally different organization of the subunits
      within a dimer in the two alphaMs.

PMID- 9016814
TI  - Substrate specificity modification of the stromal glycerol-3-phosphate
      acyltransferase.
AB  - The stromal glycerol-3-phosphate acyltransferases (GPATs; EC 2.3.1.15) from
      spinach (Spinacia oleracea) and squash (Cucurbita moschata) were expressed in
      Escherichia coli and their activities with palmitoyl-CoA and oleoyl-CoA compared.
      The GPAT from squash, a chilling-sensitive plant, was found to have the greatest
      difference in activities between the two substrates, using palmitoyl-CoA over
      three times faster than oleoyl-CoA. In contrast, the enzyme from spinach, a
      chilling-tolerant plant, preferred oleoyl-CoA over palmitoyl-CoA. By using
      conserved restriction endonuclease sites each of the two genes was divided into
      three fragments of roughly equal size and recombined to create six different
      chimeras. All chimeras retained a large portion of their original activity but in
      most cases the specificity was greatly altered. The central third of the protein
      was found to contain the structural features which determine substrate
      specificity of the wild-type GPATs. Two of the chimeras, which have a spinach
      derived central region and a squash-derived carboxyl region, were found to have
      greatly enhanced specificities for 18:1 acyl chains, potentially making them
      ideal for decreasing the level of saturation of plant membrane lipids through
      genetic engineering.

PMID- 9016815
TI  - Oxygen activation by cytochrome P450BM-3: effects of mutating an active site
      acidic residue.
AB  - A highly conserved acid residue is found in the I-helix of most cytochrome P450s
      and has been suggested to play a critical function in oxygen activation and
      substrate hydroxylation in these monooxygenases. We have investigated this
      hypothesis for cytochrome P450BM-3 by replacing the naturally occuring glutamate
      at position 267 with a glutamine residue. In the case of P450BM-3, mutation of
      the glutamate to glutamine as position 267 drastically reduces the catalytic
      activity of the enzyme when palmitate is used as a substrate for hydroxylation.
      On the other hand, the activity change toward laurate hydroxylation is relatively
      small. The much slower catalytic turnover by the mutant enzyme in palmitate
      hydroxylation compared with wild type allows the observation of a new spectral
      intermediate in the hemoprotein. This intermediate is similar to that observed in
      the corresponding active site acid-to-amide replacement in cytochrome P450cam (N.
      C. Gerber and S. G. Sligar (1994) J. Biol. Chem. 269, 4260-4266). Also, in
      analogy with P450cam, this mutation does not lead to any side oxidation processes
      which produce hydrogen peroxide. Interestingly, however, the alteration in the
      active site structure which is implied by the change in regio specificity may
      also effect substrate packing thus leading to the uncoupling of the enzyme to
      produce additional water rather than a commitment to substrate oxidation. In
      addition, the distribution of hydroxylation products is altered by this mutation,
      suggesting some perturbation of the recognition property in P450BM-3.

PMID- 9016816
TI  - Effects of fatty acids and ketone bodies on cytochromes P450 2B, 4A, and 2E1
      expression in primary cultured rat hepatocytes.
AB  - CYP2B, CYP4A, and CYP2E1 mRNA levels are elevated in response to
      pathophysiological conditions, such as diabetes, high-fat diet, and fasting, in
      which lipids and ketone bodies are increased. In order to avoid confounding
      hormonal effects, we utilized primary rat hepatocytes to examine whether ketone
      bodies or fatty acids altered CYP2B, CYP4A, or CYP2E1 expression. Ketone bodies
      increased CYP2B mRNA and protein levels, but failed to alter CYP4A or CYP2E1
      expression. Straight-chain saturated fatty acids, C8 to C16, increased levels of
      CYP2B and CYP4A mRNA, but not CYP2E1 mRNA. Treatment with octanoylcarnitine, a
      mitochondrial beta-oxidation inhibitor, in combination with hexadecanoate
      increased CYP2B and CYP4A expression approximately 1.4-fold over that observed
      with hexadecanoate alone, suggesting that mitochondrial conversion of fatty acids
      to ketone bodies was not required for enhanced CYP2B expression and that
      mitochondrial beta-oxidation decreased intracellular fatty acid levels and
      thereby lowered CYP2B expression. Undecynoic acid or aminobenzotriazole treatment
      increased CYP2B mRNA levels, consistent with these compounds inhibiting the
      initial CYP4A-catalyzed step in the conversion of monocarboxylic to dicarboxylic
      acids and thereby decreasing peroxisomal beta-oxidation and increasing
      intracellular fatty acid levels. Addition of glycerol, which suppresses fatty
      acid synthesis by inhibiting conversion of lactate to pyruvate, decreased basal
      expression of CYP2B and CYP4A but did not alter CYP2E1 expression. Pyruvate, but
      not lactate, completely prevented the glycerol-mediated decrease in CYP2B
      expression. These results provide evidence that intracellular levels of fatty
      acids and ketone bodies regulate the expression of CYP2B but not CYP2E1.

PMID- 9016817
TI  - Effect of calcium on the reversible thermal inactivation of lignin peroxidase.
AB  - This study investigated the effects of calcium on the thermal inactivation of
      lignin peroxidase from Phanerochaete chrysosporium. The monophasic loss of
      veratryl alcohol oxidase activity corresponded to the loss of calcium when the
      enzyme was thermally inactivated. Addition of calcium slowed and oxalate and EGTA
      increased the apparent inactivation rate. The thermally inactivated lignin
      peroxidase could be readily reactivated by addition of Ca2+. The amount of
      activity recovered was dependent on temperature, Ca2+ concentration, and
      incubation conditions. Enzyme activity could be recovered up to 95% of its
      original value by addition of Ca2+ when lignin peroxidase was depleted of Ca2+ by
      incubation with EGTA. Although heme absorbance decreased when the enzyme was
      thermally inactivated, the amount of iron in the enzyme did not change. Changes
      in the heme environment of the inactivated enzyme were suggested by changes in
      the electronic absorption in which the Soret band shifted from 408 to 410 nm, the
      absorption at 502 nm shifted to 532 nm, and the absorption at 634 nm disappeared
      upon inactivation. Upon the addition of Ca2+, the bands returned to the original
      wavelength. Therefore, it is proposed that the inactivation mechanism of lignin
      peroxidase is that the loss of calcium causes heme environmental changes
      resulting in the loss of enzyme activity.

PMID- 9016818
TI  - Immunological analysis of two calpain-like Ca2+-dependent proteinases from
      lobster striated muscles: relationship to mammalian and Drosophila calpains.
AB  - Lobster skeletal muscles contain four Ca2+-dependent cysteine proteinases (CDPs
      I, IIa, IIb, and III) that degrade myofibrillar proteins. Lobster CDPs share many
      properties with calpains from vertebrate tissues, but differ in native mass and
      subunit composition. Recently, cDNAs encoding a calpain-like protein (Dm-calpain;
      91.5 or 94 kDa) have been isolated from fruit fly, Drosophila melanogaster. To
      further clarify the relationship between invertebrate CDPs and mammalian
      calpains, antibodies specific for mu-, m-, p94 (nCL-1), and Dm-calpains and
      lobster CDP IIb (native M(r) 195,000, subunit M(r) 95,000) were used in
      immunoblots to test for antigenic cross-reactivity. No common epitopes were found
      between CDP IIb and vertebrate calpains. However, polyclonal antibodies to CDP
      IIb cross-reacted strongly with a C-terminal 70-kDa portion of Dm-calpain
      expressed in Escherichia coli. Conversely, polyclonal antibodies to Dm-calpain
      recognized CDP IIb. A second CDP, CDP IIa (native M(r) 125,000), was partially
      purified from lobster muscle; enzyme activity coeluted with a 60-kDa polypeptide
      using anion-exchange chromatography. The 60-kDa protein reacted with a polyclonal
      antibody raised against a 20-amino acid peptide sequence found around the
      catalytic cysteine residue of mu- and m-calpains, but not with antibodies raised
      against other regions of mu- or m-calpain or with the anti-CDP IIb antibody.
      These results suggest that (1) the CDP IIb is the homolog of Drosophila calpain
      in crustaceans and (2) the active site regions of CDP IIa and mu- and m-calpains
      are similar.

PMID- 9016819
TI  - Inhibition of rat and human cytochrome P4502E1 catalytic activity and reactive
      oxygen radical formation by nitric oxide.
AB  - Nitric oxide (NO) reacts with heme-containing enzymes, including certain isoforms
      of cytochrome P450. Cytochrome P4502E1 (CYP2E1) is induced by ethanol and plays
      an important role in the toxicity of ethanol and other hepatotoxins. CYP2E1 is
      also very effective in generating reactive oxygen intermediates such as
      superoxide radical and H2O2, oxidizing ethanol to the 1-hydroxyethyl radical, and
      has a high NADPH oxidase activity. The effect of NO on CYP2E1 catalytic activity
      and generation of reactive oxygen intermediates was evaluated. Incubating liver
      microsomes isolated from rats treated with pyrazole to induce high levels of
      CYP2E1, with gaseous NO or NO released from a variety of NO donors such as SNAP,
      DEA/NO, spermine/NO, and GSNO, resulted in a loss of CYP2E1 catalytic activity
      with specific substrates such as p-nitrophenol or dimethylnitrosamine. Trapping
      of NO with hemoglobin resulted in protection of CYP2E1 activity against the
      inactivation by NO. There was no effect by analogues of the donors which do not
      release NO nor was there any effect by NO on NADPH-cytochrome P450 reductase
      activity. Inactivation of CYP2E1 by NO was not prevented by superoxide dismutase
      or catalase, suggesting that superoxide, H2O2, or peroxynitrite were not
      responsible for the actions of NO. The inactivated CYP2E1 was not degraded nor
      did it lose its epitope sites as shown by Western blot analysis. Associated with
      loss of CYP2E1 catalytic activity was a decrease in the formation of superoxide
      radical and H2O2, in microsomal lipid peroxidation catalyzed by low, but not high
      concentration of iron, and in consumption of NADPH. Oxidation of ethanol to the 1
      hydroxyethyl radical was also inhibited by NO. ESR experiments indicated the
      formation of stable heme-NO complexes with CYP2E1. NO appears to compete with O2
      and CO for binding to CYP2E1 as incubation with gaseous NO, or NO donors
      inhibited formation of the characteristic CO binding spectrum of P450. Microsomes
      isolated from a stably transfected HepG2 cell line expressing only CYP2E1 were
      also inactivated by NO, validating interaction of NO with this isoform of P450.
      These results indicate that NO inhibits CYP2E1 catalytic activity and generation
      of reactive radical intermediates. NO may prevent toxicity of agents which
      require bioactivation by P450 isoforms such as CYP2E1 and in generation of
      reactive intermediates by CYP2E1.

PMID- 9016820
TI  - Inhibition of squalene synthase but not squalene cyclase prevents mevalonate
      mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis
      at a posttranscriptional level.
AB  - Previously, we found that mevalonate-derived products together with an oxysterol
      regulated reductase synthesis at a posttranscriptional level. To determine which
      products were responsible for this regulation, either the squalene synthase
      inhibitor zaragozic acid A or the squalene cyclase inhibitor 4,4,10-beta
      trimethyl-trans-decal-3beta-ol (TMD) was added to lovastatin-treated Syrian
      hamster cells in conjunction with mevalonate. Mevalonate alone decreased
      reductase synthesis 50% compared with lovastatin-treated cells. In contrast, when
      both zaragozic acid A and mevalonate were added to lovastatin-treated cells,
      there was no change in reductase synthesis. With either treatment, reductase mRNA
      levels did not change compared with lovastatin-treated cells. When both 25
      hydroxycholesterol and mevalonate were added to lovastatin-treated cells,
      reductase synthesis and mRNA levels were decreased 95 and 50%, respectively. The
      10-fold difference between changes in reductase synthesis and mRNA levels under
      these conditions reflects a specific effect of mevalonate-derived isoprenoids on
      reductase synthesis at the translational level. In contrast, coincubation of
      cells with mevalonate plus 25-hydroxycholesterol in the presence of zaragozic
      acid decreased reductase synthesis and mRNA levels 60 and 50%, respectively,
      compared with lovastatin-treated cells. Moreover, degradation of reductase was
      increased approximately 7-fold in cells treated with mevalonate alone but only 3
      fold in cells treated with mevalonate and zaragozic acid A. These results
      indicate that isoprenoid products between mevalonate and squalene affect
      reductase at a posttranslational level by increasing degradation but do not
      regulate reductase synthesis at a posttranscriptional level. In contrast, when
      both TMD and mevalonate were added to lovastatin-treated cells, reductase
      synthesis was decreased approximately 50% with no corresponding decrease in
      reductase mRNA levels, similar to mevalonate only. Reductase degradation was
      increased approximately 7-fold under these conditions. Cellular incubation in
      TMD, mevalonate, and 25-hydroxycholesterol decreased reductase synthesis and mRNA
      levels 95 and 50%, respectively. From these results we concluded that mevalonate
      derived nonsterols synthesized between squalene and lanosterol decrease reductase
      synthesis at a translational level-either alone or in combination with 25
      hydroxycholesterol-and also increase reductase degradation.

PMID- 9016821
TI  - Coding sequence of a hyaluronan synthase homologue expressed during expansion of
      the mouse cumulus-oocyte complex.
AB  - Maturation of mammalian cumulus cell-oocyte complex in the preovulatory follicle
      involves the deposition of a hyaluronan-rich extracellular matrix by the cumulus
      cells. In this study, we report the complete coding sequence of a novel mouse
      hyaluronan synthase homologue expressed in cumulus cell-oocyte complexes induced
      to expand in vivo. The time frame of mRNA expression of this molecule correlates
      well with previous biochemical and immunohistochemical findings on the initiation
      of hyaluronan synthesis in maturing preovulatory follicles. Evolutionary
      comparison of the vertebrate hyaluronan synthase homologues indicates that there
      are at least two genes that code for these proteins.

PMID- 9016822
TI  - Subtle differences between human and rabbit neutrophil receptors shown by the
      secretagogue activity of constrained formyl peptides.
AB  - Stereochemically constrained extended beta-antiparallel and folded beta-turn
      analogs of the chemotactic agent N-formyl-Met-Leu-Phe-OH were tested for their
      ability to induce the release of beta-glucuronidase from human and rabbit
      neutrophils. Selected biologically active peptides were further examined for
      their capacity to inhibit the binding of f-Met-Leu-[3H]Phe to whole human
      neutrophils at 4 degrees C. The results suggest that Dpg2 analogs with the
      extended backbone are significantly more potent in human peripheral blood
      neutrophils than the folded beta-turn analogs. Surprisingly, in rabbit peritoneal
      neutrophils, the extended Dpg2 analog appears to be marginally less active than
      the flexible parent peptide and the folded Ac6c2 analog. In human neutrophils,
      the secretagogue activity increases in the following order with alteration in the
      C-terminal functions: -CONH2 < -COOMe < -COOH << -COOBzl. However, this order of
      potency differs from that observed for the rabbit formyl peptide receptor (-COOH
      < -COOMe < -CONH2 << -COOBzl). In human neutrophils, the peptides' ability to
      compete for the receptor binding site of f-Met-Leu-[3H]Phe correlates well with
      their secretagogue potency. The results provide convincing evidence for the
      existence of subtle differences between human peripheral blood neutrophils and
      rabbit peritoneal neutrophils with regard to ligand-receptor interactions of
      constrained chemotactic peptides. What is new and novel in this report is that
      constrained peptides can distinguish between the rabbit and human chemotactic
      peptide receptors which have so far been believed to have similar response to
      secretagogue agents. The data emphasize that directly relating the secretagogue
      activity observed in rabbit neutrophils to that observed in human neutrophils may
      not be unequivocal.

PMID- 9016823
TI  - Human hepatic microsomal epoxide hydrolase: comparative analysis of polymorphic
      expression.
AB  - Interindividual variation in the expression of human microsomal epoxide hydrolase
      (mEH) may be an important risk factor for chemically induced toxicities,
      including cancer and teratogenesis. In this study, phenotypic variability and mEH
      genetic polymorphisms were examined in a bank of 40 transplant-quality human
      liver samples. Immunochemically determined protein content, enzymatic activities,
      polymorphic amino acids, as well as mEH RNA levels were evaluated in parallel.
      Enzymatic activity was assessed using (+/-)-benzo[a]pyrene-4,5-epoxide at 2
      substrate concentrations. The relative hydrolyzing activities obtained using
      saturating substrate levels were highly correlated (r = 0.85) with results
      derived from limiting substrate concentrations and exhibit approximately an 8
      fold range in activity levels across the panel of 40 liver samples. mEH enzyme
      activity also demonstrated strong correlation (r > or = 0.74) with an 8.4-fold
      variation determined for mEH protein content within the same samples. However,
      these protein/activity measurements were poorly correlated (r < or = 0.23) with
      mEH RNA levels, which exhibited a 49-fold variation. Two common polymorphic amino
      acid loci in the mEH protein did not exclusively account for variation in
      enzymatic activity, although this conclusion is confounded by heterozygousity in
      the samples. These data demonstrate the extent of hepatic mEH functional
      variability in well-preserved human tissues and suggest that polymorphism of mEH
      protein expression is regulated in part by posttranscriptional controls, which
      may include nonstructural regulatory regions of the mEH transcript.

PMID- 9016824
TI  - Characterization of sphinganine kinase activity in corn shoot microsomes.
AB  - The activity of sphinganine kinase, the enzyme catalyzing the first step in the
      breakdown of the sphingoid long-chain base sphinganine by converting it to
      sphinganine 1-phosphate, was characterized in microsomes isolated from corn
      shoots. Activity was assayed by monitoring the conversion of [3H]sphinganine to
      [3H]sphinganine 1-phosphate, which was recovered in the aqueous phase following
      lipid extraction. Sphinganine kinase was found to utilize D-erythro-sphinganine
      and ATP as substrates. Maximum product formation required the presence of Mg2+.
      The apparent Km for ATP was 0.81 mM. GTP also served as a source of phosphate,
      whereas CTP and UTP were not effective substrates in this assay. Maximum product
      formation was observed at sphinganine concentrations of approximately 100 microM.
      Results of competition experiments suggested that the enzyme could also
      phosphorylate D-erythro-sphingosine but not DL-threo-sphinganine or D
      phytosphingosine. Enzyme activity was greatest in the microsomal fraction
      obtained by differential centrifugation and was localized to the Golgi and
      endoplasmic reticulum using marker enzymes. The specific activity of the enzyme
      under optimal conditions was 1.08 nmol/min x mg protein, a value 25-fold higher
      than that reported for preparations from brain tissue. Fumonisin, a mycotoxin
      that disrupts sphingolipid metabolism, did not alter sphinganine kinase activity
      in vivo or in vitro. The results of this study demonstrate, for the first time,
      the presence of sphinganine kinase activity in plant tissue and suggest that the
      properties of the kinase from corn microsomes are distinct from those of the
      mammalian and protistan enzymes in some respects.

PMID- 9016825
TI  - Crovidisin, a collagen-binding protein isolated from snake venom of Crotalus
      viridis, prevents platelet-collagen interaction.
AB  - By means of liquid chromatography consisting of gel filtration, anionic exchange,
      and C8 reverse-phase HPLC, a selective inhibitor of collagen-induced platelet
      aggregation, named crovidisin, has been purified to homogeneity from the venom of
      Crotalus viridis snake. Crovidisin is a single-chain, 53-kDa protein with a
      selective inhibitory activity on collagen-induced aggregation of human washed
      platelets without affecting those elicited by thrombin, sodium arachidonate, and
      ADP. Partial sequencing of tryptic digests of crovidisin reveals that partial
      sequence of crovidisin appears to be identical to that of catrocollastatin, a
      collagen antagonist occurring in the venom of Crotalus atrox snake. Crovidisin
      dose-dependently blocked aggregation of human washed platelets triggered by 5 and
      10 microg/ml of collagen with IC50 of 0.17 and 0.47 microM, respectively. Not
      only platelet aggregation but also release reaction, thromboxane formation, and
      increase of intracellular Ca2+ level of platelets in response to collagen were
      all completely abolished by crovidisin. In the presence of crovidisin, the Mg2+
      dependent adhesion of platelets to collagen was diminished in a dose-dependent
      manner, while the glycoprotein IIb/IIIa-mediated platelet-fibrinogen interaction
      was unaffected. When collagen was pretreated with crovidisin and followed by
      three washes with phosphate-buffered saline, the antiadhesion activity of
      crovidisin was unaffected. In addition, collagen fibers emitted fluorescence
      after incubation with fluorescein isothiocyanate-conjugated crovidisin,
      indicating that crovidisin binds directly to collagen fibers. In conclusion,
      crovidisin blocks the interaction between platelets and collagen fibers through
      its binding to collagen fibers, resulting in the blockade of collagen-mediated
      platelet functions such as adhesion, release reaction, thromboxane formation, and
      aggregation.

PMID- 9016826
TI  - Genomic organization of the zinc-endopeptidase astacin.
AB  - The crayfish digestive protease astacin is the first described member of the
      astacin family of zinc-endopeptidases, for which it is regarded as a prototype.
      We have isolated and characterized the genomic sequence of astacin which spans a
      region of 2616 bp. The coding sequence is distributed over five exons and is
      interrupted by four introns. It was observed that structurally and functionally
      essential units of the protein, like the three alpha-helices, the five beta
      strands, the Zn-binding motif, and the Met turn are never disrupted by introns.
      The start site of transcription was determined by primer extension analysis,
      confirming the existence of a pre-pro-protein of 49 amino acids which so far had
      not been detectable at the protein level. In addition, when compared to the amino
      acid sequence of mature astacin, a carboxy-terminal extension of two additional
      amino acids was also found. The exon-intron pattern of the astacin gene was
      compared to those of three other astacin family members with known genomic
      sequences, i.e., tolloid of Drosophila, the fish hatching enzyme LCE, and the
      human BMP1 gene. In each of the four proteins one intron was found to be inserted
      in the codon for a similar Gly residue which is highly conserved in this position
      within the astacin family.

PMID- 9016827
TI  - Intracellular and extracellular forms of alkaline pullulanase from an
      alkaliphilic Bacillus sp. S-1.
AB  - Bacillus sp.S-1 alkaline pullulanase (AP) exists in two forms: a precursor form
      (PUL-Ia, M(r) 180,000) and a processed form (PUL-Ib, M(r) 140,000). PUL-Ia was
      accumulated intracellularly in large amounts, and PUL-Ib was detected in both the
      membrane fraction and the fraction trapped between the cytoplasmic membrane and
      the cell wall. Two forms of AP were purified to homogeneity and their properties
      were compared with previously purified PUL-E (140 kDa). PUL-Ib showed similar
      properties, such as the M(r) value, the pI value (5.7), specific activity,
      substrate specificity, the NH2-terminal amino acid sequence (Phe-Leu-Asn-Met
      Ser), and biophysical characters. However, in the case of PUL-Ia, even though the
      patterns of optimum pH and temperature, substrate specificity, and enzyme
      inhibition and activation were similar to those for PUL-Ib and PUL-E, the M(r)
      value and the pI value (5.97) were different. Furthermore, the NH2-terminal amino
      acid sequence of PUL-Ia was completely blocked, and the stabilities over pH and
      temperature ranges were decreased. The catalytic activities of PUL-Ia were
      distinguishable in the Km and Vmax values for various substrates and in the
      specific activity (71.4 U/mg) for pullulan hydrolysis. PUL-Ib and PUL-E showed 10
      fold higher specific activities (744.6 for PUL-E and 736 for PUL-Ib) than PUL-Ia.
      However, PUL-Ia was immunologically identical to PUL-E and PUL-Ib. Therefore, it
      was concluded that PUL-Ib and PUL-E are the same form of the enzyme, suggesting
      that PUL-Ia is initially synthesized and proteolytically processed to the mature
      form of PUL-E. On the other hand, the translocation of AP required processing of
      the AP protein and the processing facilitated enzymatic activation and
      stabilization through a complete conformational change, resulting in an increase
      in affinity for substrates of PUL-E.

PMID- 9016828
TI  - NMR studies of inorganic phosphate compartmentation in the isolated rat liver
      during acidic perfusion.
AB  - Mitochondrial inorganic phosphate has been shown to be undetectable by 31P NMR in
      the isolated rat liver perfused under physiological conditions. Cold perfusion (4
      degrees C) with valinomycin (K+ ionophore) induced the appearance of an
      additional resonance assigned to P(i) from mitochondrial compartment (P(i,mito))
      (Thiaudiere et al., 1993, FEBS Lett. 330, 232-235). Here we have demonstrated
      that P(i,mito) can be detected by NMR under normothermic conditions (37 degrees
      C) in acidic (pH 6.5, bicarbonate-free) perfused liver using 50 nM valinomycin or
      10 microM N,N'-dicyclohexylcarbodiimide (DCCD, a mitochondrial H+-ATP synthase
      inhibitor). These conditions resulted in a significant increase in mitochondrial
      P(i) content. In the presence of valimomycin, pH values of 7.00+/-0.07 and 6.60+/
      0.10 (n = 7) for mitochondria and cytosol, respectively, were determined from the
      chemical shift values of P(i) resonances. Electron microscopy demonstrated a
      large matrix swelling under valinomycin perfusion, explaining the increased level
      of mitochondrial P(i). The amount of mitochondrial P(i) measured by NMR increased
      linearly with the cellular ATP depletion, suggesting a mitochondrial influx of
      P(i) from the cytosolic compartment with valinomycin perfusion. Moreover, the
      level of matrix P(i) was dependent on the cytosolic pH value, the resonance being
      not detectable at physiological cytosolic pH. During mitochondrial swelling, P(i)
      influx was likely to be associated with proton influx, owing to the stability of
      transmembrane pH gradient and matrix proton concentration.

PMID- 9016829
TI  - Does DsbA have chaperone-like activity?
AB  - DsbA showed chaperone-like activity similar to but weaker than that of protein
      disulfide isomerase in increasing reactivation and decreasing aggregation during
      the refolding of guanidine hydrochloride-denatured D-glyceraldehyde-3-phosphate
      dehydrogenase and rhodanese. The fact that both enzymes are devoid of disulfide
      bonds indicates the independence of the chaperone-like activity of DsbA from its
      thiol-protein oxidoreductase activity. The increased reactivation of D
      glyceraldehyde-3-phosphate dehydrogenase by DsbA can be suppressed with
      increasing concentrations of a peptide of 21 amino acid residues, suggesting that
      the peptide binding ability of DsbA is responsible for its chaperone-like
      activity.

PMID- 9016830
TI  - Relationship between oxidative stress and heme oxygenase induction by copper
      sulfate.
AB  - The effect of copper sulfate (CuSO4) on both hepatic oxidative stress and heme
      oxygenase induction was studied. A strong increase in in vivo rat liver
      chemiluminescence was observed 1 h after Cu(II) administration. To evaluate liver
      antioxidant enzymatic defenses, superoxide dismutase, catalase, and glutathione
      peroxidase activities were determined. Catalase and glutathione peroxidase were
      found to be significantly decreased 5 h after CuSO4 injection. In contrast,
      superoxide dismutase activity was increased. Heme oxygenase activity appeared 5 h
      after treatment, reaching a maximum value 18 h after CuSO4 administration. This
      induction was preceded by a decrease in the intrahepatic GSH pool and an increase
      in the generation of thiobarbituric acid reactive substances, both effects taking
      place a number of hours before induction of heme oxygenase. Administration of
      bilirubin, the end product of heme catabolism in mammals, and alpha-tocopherol, a
      widely employed antioxidant, completely prevented heme oxygenase induction as
      well as the decrease in hepatic GSH and the increase in chemiluminescence when
      administered 2 h before CuSO4 treatment. Under the same experimental conditions,
      beta-carotene showed a moderate preventive effect on both heme oxygenase
      induction and oxidative stress parameters. These data obtained with Cu(II)
      treatment are in agreement with our previous reports suggesting a correlation
      between heme oxygenase induction and oxidative stress.

PMID- 9016831
TI  - Fungal P450nor: expression in Escherichia coli and site-directed mutageneses at
      the putative distal region.
AB  - P450nor, nitric oxide reductase from Fusarium oxysporum, was expressed in the
      soluble fraction of Escherichia coli cells by modifying the N-terminal codons and
      utilizing the pCW vector. The modified P450nor purified to electrophoretic
      homogeneity had spectral and enzymatic properties identical to those of native
      P450nor obtained from the fungi. Residues 239 to 247 of the modified P450nor were
      replaced with Lys by site-directed mutagenesis. Thr-243 to His- and Arg-mutants
      were also created. Among 11 mutants, only the Thr-243 to Lys-mutant exhibited an
      absorption spectrum characteristic of a nitrogenous ligand-bound form of P450 at
      pH 8.0 in the ferric state, but the spectrum was altered to that of the wild-type
      P450nor as the pH was lowered. Other mutants had spectra typical of the low- and
      high-spin mixed form of P450 in the ferric state. In the ferrous state, all
      mutants showed the same spectrum as the wild-type P450nor. Nitric oxide reductase
      activity was considerably decreased by the replacement of Thr-243 with Lys, His,
      or Arg or Ala-239 with Lys. These findings indicate that Thr-243 is located more
      closely to the heme iron than other residues in the putative distal helix of
      P450nor and plays an important role in the catalytic activity, but a specific
      difference in the structure of the heme pocket from other P450s is suggested.

PMID- 9016832
TI  - In vivo phosphorylation of phosphoenolpyruvate carboxylase in guard cells of
      Vicia faba L. is enhanced by fusicoccin and suppressed by abscisic acid.
AB  - Plants regulate water loss and CO2 gain by modulating the aperture sizes of
      stomata that penetrate the epidermis. Aperture size itself is increased by
      osmolyte accumulation and consequent turgor increase in the pair of guard cells
      that flank each stoma. Guard cell phosphoenolpyruvate carboxylase (PEPC, EC
      4.1.1.31), which catalyzes the regulated step leading to malate synthesis, is
      crucial for charge and pH maintenance during osmolyte accumulation. Regulation of
      this cytosolic enzyme by effectors is well documented, but additional regulation
      by posttranslational modification is predicted by the alteration of PEPC kinetics
      during stomatal opening (FEBS Lett. 352, 45-48). In this study, we have
      investigated whether this alteration is associated with the phosphorylation
      status of this enzyme. Using sonicated epidermal peels ("isolated" guard cells)
      preloaded with 32PO4, we induced stomatal opening and guard cell malate
      accumulation by incubation with 5 microM fusicoccin (FC). In corroboratory
      experiments, guard cells were incubated with the FC antagonist, 10 microM
      abscisic acid (ABA). The phosphorylation status of PEPC was assessed by
      immunoprecipitation, electrophoresis, immunoblotting, and autoradiography. PEPC
      was phosphorylated when stomata were stimulated to open, and phosphorylation was
      lessened by incubation with ABA. Thus, we conclude that regulation of guard cell
      PEPC in vivo is multifaceted; the effects of regulatory metabolites and the
      activation status of the enzyme are integrated to control malate synthesis. These
      results, together with the coincident alteration in the kinetics of the enzyme
      (FEBS Lett. 352, 45-48), constitute the first unequivocal demonstration of
      regulatory posttranslational modification of a guard cell protein that is
      specifically implicated in stomatal movements.

PMID- 9016833
TI  - A soluble ecto-ATPase from Tetrahymena thermophila: purification and similarity
      to the membrane-bound ecto-ATPase of smooth muscle.
AB  - For the first time, a soluble, dedicated E-type ecto-ATPase has been identified
      and purified. This fully soluble ecto-ATPase is released into the growth media of
      the single-celled eukaryote, Tetrahymena, at a constant rate over time
      (independent of the growth phase of the cells) and it has characteristics similar
      to those previously described for the membrane-bound ecto-enzyme in Tetrahymena.
      It was purified by a combination of ion-exchange, size exclusion, and affinity
      chromatography and nondenaturing gel electrophoresis. Its molecular weight was
      determined to be approximately 66,000 Da by denaturing gel electrophoresis and
      approximately 69,000 Da by size exclusion chromatography of the native form. The
      purified soluble enzyme displays the general characteristics of a dedicated E
      type ecto-ATPase such as Ca2+ or Mg2+ dependence, hydrolysis of ATP and other
      nucleoside triphosphates (but not nucleoside diphosphates) and insensitivity to
      common ATPase inhibitors (vanadate, azide, ouabain, N-ethylmaleimide and p
      chloromercuriphenyl sulfonate). It was further shown to be immunologically
      similar (by polyclonal antibodies) to both the membrane-bound ecto-ATPase of
      chicken gizzard smooth muscle (66 kDa) and a 66-kDa protein in Tetrahymena plasma
      membranes. The ecto-ATPase enzyme activity was also shown to be present in both
      the body plasma membrane and ciliary plasma membrane fractions but the body
      membrane had slightly higher specific activities. We propose that this ecto
      ATPase of Tetrahymena may play a role in inactivating purinergic signals, such as
      in their chemorepulsion responses to external GTP and ATP. It may also play a
      minor role in extracellular nucleotide scavenging.

PMID- 9016835
TI  - On the synthesis of neurotransmitter receptor agonists with antagonist potential.
AB  - The synthesis of a new type of antagonist is described, capable of inactivating
      neuroreceptors with heretofore unattainable selectivity and permanence. These
      antagonists are referred to as mazek agonists (i.e. direct, inhibitory agonists)
      as they have the high receptor affinity and initial receptor-stimulatory effect
      of direct agonists and are positively coupled to effector systems. However, like
      direct antagonists, they have a high receptor affinity and the potential to
      inhibit or prevent receptor stimulation. The synthesis of the present compounds
      consisted of the covalent attachment of a tethered dye to three different
      neurotransmitter analogues, resulting in dye-neuropeptide conjugates with a high
      affinity for the FMRFa receptor. The dye was prepared from azure B (Az), the
      neurotransmitter was the neuropeptide FMRFamide (FMRFa), and the dye-neuropeptide
      conjugates synthesized were Az-CFMRFa; Az-CFMRF and Az-CLRFa. In this procedure,
      the analogues serve as carrier molecules, bound at one end to the receptor and at
      the other end to the dye, which is thereby brought into close contact with the
      receptor. The receptor can then be inactivated by singlet oxygen generated by
      laser irradiation of the photosensitized receptor.

PMID- 9016834
TI  - Release of [3H]dopamine from striatal and cerebral cortical slices from rats with
      thioacetamide-induced hepatic encephalopathy: different responses to stimulation
      by potassium ions and agonists of ionotropic glutamate receptors.
AB  - The effects of depolarizing stimuli; high (50 mM) potassium ions and the
      glutamate receptor agonists N-methyl-D-aspartate, kainate and 2-amino-3-hydroxy-5
      methyl-4-isoxazolepropionate (AMPA) on the release of newly-loaded [3H]dopamine
      were studied in frontal cortical and striatal slices from control rats and from
      rats with acute hepatic encephalopathy induced with a hepatotoxin, thioacetamide.
      Hepatic encephalopathy enhanced the stimulatory effect of potassium ions by 20%
      in striatal slices and by 34% in frontal cortical slices. In striatal slices the
      stimulatory effects of N-methyl-D-aspartate and kainate were depressed in hepatic
      encephalopathy by 46% and 21%, respectively, which may be taken to reflect
      impaired modulation of striatal dopamine release by glutamate acting at N-methyl
      D-aspartate or kainate receptors. In frontal cortical slices, the stimulatory
      effect of kainate was enhanced by 35% in hepatic encephalopathy but N-methyl-D
      aspartate-stimulated release was not affected. The release evoked by 2-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate was not affected in hepatic encephalopathy
      in either brain region. Stimulation of dopamine release in the frontal cortex by
      depolarization or glutamate acting at kainate receptors could inhibit the
      activity of descending corticostriatal glutamatergic pathways, further impairing
      regulation of dopamine release by glutamate in the striatum.

PMID- 9016836
TI  - Characterization of brain beta-carboline-2-N-methyltransferase, an enzyme that
      may play a role in idiopathic Parkinson's disease.
AB  - The activity of beta-carboline-2-N-methyltransferase results in the formation of
      neurotoxic N-methylated beta-carbolinium compounds. We have hypothesized that
      these N-methylated beta-carbolinium cations may contribute to the development of
      idiopathic Parkinson's disease. This report describes experiments undertaken to
      optimize assay conditions for bovine brain beta-carboline-2-N-methyltransferase
      activity. The activity of beta-carboline-2-N-methyltransferase is primarily
      localized in the cytosol, has a pH optimum of 8.5-9, and obeys Michaelis-Menten
      kinetics with respect to its substrates, 9-methylnorharman (9-MeNH) and S
      adenosyl-L-methionine (SAM). Kinetic constants, KM and Vmax, with respect to 9
      MeNH, are 75 microM and 48 pmol/h/mg protein, respectively. The KM for SAM is 81
      microM and the Vmax is 53 pmol/h/mg protein. In addition, enzyme activity is
      inhibited by S-adenosyl-L-homocysteine (SAH) or zinc, and is increased 2-fold in
      the presence of iron or manganese. Enzyme characterization is a prerequisite to
      the purification of this N-methyltransferase from bovine brain as well as
      comparison of its activity in human brain from control and Parkinson's disease
      individuals.

PMID- 9016837
TI  - Interactions of triethyltin-chloride (TET) with the energy metabolism of cultured
      rat brain astrocytes: studies by multinuclear magnetic resonance spectroscopy.
AB  - The effect of triethyltin-chloride (TET), a highly neurotoxic compound, on the
      cellular metabolism of rat brain astrocytes in vitro was examined by nuclear
      magnetic resonance (NMR) spectroscopy. 5-week-old cultures were exposed to TET
      (0.2-40 microM) either for (1) acute (3h), (2) 24 h, or (3) chronic treatment (8
      d). Cells were labeled with 1-(13)C-glucose, cell extracts were prepared and 31P,
      1H, and 13C spectra were analyzed. Cytotoxic effects of TET were assessed by
      vital dye uptake assay using neutral red (NR) and by exclusion of trypan blue
      (TB). Cells were examined ultrastructurally by electron microscopy. The data show
      that the major target of TET at concentrations already causing morphological
      effects on cultured astrocytes is not the energy metabolism, but that TET rather
      alters the intracellular concentrations of organic osmolytes, such as myo
      inositol, taurine and hypotaurine, which are part of the control of ion and
      volume regulation and osmotic balance in astrocytes.

PMID- 9016838
TI  - Identification of monoclonal antibody At5 as a new member of HNK-1 antibody
      family: the reactivity with myelin-associated glycoprotein and with two brain
      specific proteoglycans, phosphacan and neurocan.
AB  - Monoclonal antibody At5 was primarily developed against chordin, a notochord
      specific antigen of Acipenseridae (sturgeon fishes). In higher vertebrates the
      antibody reacted mainly with neural tissue antigens. In this study we have shown
      that the specificity of monoclonal antibody At5 is similar to that of antibodies
      of HNK-1 family which react with two glycolipids and with several high molecular
      weight glycoconjugates of neural tissue. We have demonstrated by protein
      sequencing and immunoblotting that one of At5 target antigens of human brain is
      dMAG, a derivative of myelin-associated glycoprotein. In the preparations of At5
      antigens proteoglycans phosphacan and neurocan were identified by immunoblotting
      with specific monoclonal antibodies 6B4 and 1G2, respectively. The distribution
      of At5 and 6B4 immunoreactivity was studied on sections of mixed
      oligoastrocytoma. Oligodendroglioma area of this tumor was intensely stained with
      both antibodies, whereas astrocytoma area did not exhibit any At5 or 6B4
      immunoreactivity.

PMID- 9016839
TI  - Neurochemical changes in cerebellum of goldfish exposed to various temperatures.
AB  - Acclimation of goldfish at 35 degrees C increased the cerebellar content of
      aspartate, glutamate, and taurine and [3H]glutamate uptake. Acclimation at 4
      degrees C increased the levels of glutamine, serine, and alanine and glutamine
      synthetase (GS) activity. Adenosine content increased in cerebellum of fish
      acclimated to warm temperature. K+-evoked release of endogenous and exogenous
      glutamate from cerebellar slices increased in fish acclimated at 35 degrees C
      compared to 4 degrees C. The basal level of cyclic adenosine 3':5'-monophosphate
      (cAMP) in perfused cerebellar slices in fish acclimated at 35 degrees C was much
      higher than in fish acclimated at 5 degrees and 22 degrees C. It is concluded
      that variations of environmental temperature produces large neurochemical changes
      in goldfish cerebellum.

PMID- 9016840
TI  - Clozapine and some other antipsychotic drugs may preferentially block the same
      subset of GABA(A) receptors.
AB  - Selective blockade of a subset of GABA(A) receptors may be involved in the
      antipsychotic effects of Clozapine and several other antipsychotic drugs. Seven
      antipsychotic drugs, and 11 drugs classified as antidepressants that only
      partially reverse the inhibitory effect of 1 microM GABA on [35S]TBPS binding, do
      not yield additive reversal when tested pairwise with Clozapine, which also only
      partially reverses the inhibitory effect of GABA. This suggests that all of these
      antipsychotic/antidepressant drugs may block a common subset of GABA(A)
      receptors. DMCM and Ro 5-4864 are also partial reversers of GABA's inhibitory
      effect, but they yield additive reversals when tested pairwise with the
      antipsychotic/antidepressant drugs, and also with each other, suggesting that
      DMCM, Ro 5-4864, and the antipsychotic drugs define three heterogeneous subsets
      of GABA(A) receptors, with variable overlap, depending on the drug. Several
      potent ligands for benzodiazepine binding sites can block the GABA inhibitory
      effects of DMCM and Ro 5-4864, but with different patterns: the ligands generally
      blocked DMCM less potently, but more completely than Ro 5-4864. Ro 5-4864 was not
      blocked by Flumazenil or CGS-8216, ligands that potently blocked DMCM. Nine
      additional antipsychotic/antidepressant drugs, as well as Clozapine, and 7
      "classical" GABA(A) receptor blockers, all of which reversed GABA nearly
      completely, when tested at lower concentrations that only reverse approximately
      20-35%, yielded almost complete additivity when tested pairwise with DMCM or Ro
      54864. Another convulsant benzodiazepine, KW-1937, a positional isomer of
      Brotizolam, fully reverses the inhibitory effect of 1 microM GABA. At a lower
      concentration yielding about 50% reversal, KW-1937 is completely additive with
      DMCM, but entirely nonadditive with Ro 5-4864. The 50% reversal obtained with KW
      1937 was potently blocked by Triazolam, but with a plateau similar to that
      obtained with Ro 5-4864. The results with KW- 1937 suggest that its 50% reversal
      largely corresponds to the reversal obtained with Ro 5-4864, and that virtually
      all of the [35S]TBPS binding sites inhibited by 1 microM GABA are coupled to
      benzodiazepine binding sites. The fraction of GABA(A) receptors preferentially
      blocked by all the antipsychotic/antidepressant drugs, roughly 25% of the
      [35S]TBPS binding sites inhibited with 1 microM GABA, are sensitive to KW-1937,
      but not to DMCM or to Ro 5-4864.

PMID- 9016841
TI  - Upregulation of (+)-7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin binding
      following intracerebroventricular administration of a nitric oxide generator.
AB  - Nitric oxide modulation of dopamine D2 and D3 receptor binding was examined using
      [125I]epidepride (D2) and (+)7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin
      ([3H](+)-7-OH-DPAT, D3). Nitric oxide, generated by i.c.v. injection of S-nitroso
      N-acetyl-penicillamine (SNAP; 5 microg or 10 microg), significantly increased the
      density of [3H](+)-7-OH-DPAT binding sites (39% and 134%, respectively) in the
      striatum 24 hours post-injection in the absence of Gpp(NH)p, representing an
      upregulation of either D3 receptors or high affinity D2 receptors. In the
      presence of 10 microM Gpp(NH)p, D3 receptor upregulation was maintained in both
      the 5 microg (increased 35%) and 10 microg SNAP (increased 44%) groups. [3H](+)-7
      OH-DPAT binding was reduced in both striatum and nucleus accumbens in the
      presence of 10 microM Gpp(NH)p compared to binding in the absence of Gpp(NH)p,
      suggesting an upregulation of D3 receptors. Administration of SNAP did not alter
      total specific [125I]epidepride binding in either brain region. These data
      suggest that; 1) D3 receptor density is modified following nitric oxide
      generation, and 2) the density of high affinity D2 receptors identified by
      [3H](+)-7-OH-DPAT increases in the striatum, but decreases in the nucleus
      accumbens.

PMID- 9016842
TI  - Effect of corticotropin releasing factor (CRF) injected into the median eminence
      on LH secretion in male rats.
AB  - We determined the dose-response relationship and examined the time-related effect
      of CRF (corticotropin releasing factor) injected directly into the Median
      Eminence (ME) on LH secretion in conscious intact and castrated male rats. Doses
      of 0.25, 0.75, 1, and 1.5 nmol CRF dissolved in 1 microl of saline (or saline
      only in the controls) were injected into the ME and blood samples collected 30,
      60, 90, and 120 min postinjection to determine by RIA serum LH. CRF at doses of
      0.75, 1 and 1.5 nmol significantly decreased serum LH in castrated and intact
      animals. The lower dose of CRF did not decrease LH in the two groups studied. The
      results suggest that in males as in females, CRF inhibits by itself LH secretion,
      at least in part, by a central action in the ME; the inhibitory effect of CRF on
      LH is similar in castrated and intact males; the dose of 0.25 nmoles of CRF was
      ineffective in decreasing LH and finally that CRF at ME levels may participate in
      a variety of stress-related responses, including reproduction inhibition, through
      LH suppression.

PMID- 9016843
TI  - Ganglioside spinal cord changes in chronic relapsing experimental allergic
      encephalomyelitis induced in the Lewis rats.
AB  - Chronic relapsing experimental allergic encephalomyelitis (CREAE) was induced in
      Lewis rats by inoculation with guinea-pig myelin and complete Freund's adjuvant
      followed by treatment with low-dose cyclosporin A. Rats were sacrified at
      different phases of the disease (just before the onset of clinical signs, during
      the first clinical episode of CREAE and during the first recovery). Gangliosides
      were extracted from the spinal cord, analysed after purification by two
      dimensional chromatography and quantified densitometrically. An increase of GM 1,
      the main rat myelin ganglioside, and a decrease of GT1b, suggested to play a role
      in mediating the interactions between oligodendroglia and axons, were observed
      during the development of the CREAE. These findings indicating significant
      ganglioside changes in CREAE give further support to the concept concerning the
      involvement of gangliosides in autoimmune demyelination.

PMID- 9016844
TI  - Effect of guanine nucleotides on [3H]glutamate binding and on adenylate cyclase
      activity in rat brain membranes.
AB  - GMP-PNP, a non-hydrolyzable analog of GTP binds tightly to G-protein in the
      presence of Mg2+, so that the binding is stable even after exhaustive washings.
      This property was exploited to prepare membrane samples of rat brain where G
      protein GTP-binding sites were saturated with GMP-PNP. Experiments carried out
      with these membranes showed that GTP, GMP-PNP, GDP-S and GMP (1 mM) inhibit the
      sodium-independent [3H]glutamate binding by 30-40% [F(4,40) = 5.9; p < .001],
      whereas only GMP-PNP activates adenylate cyclase activity [F(6,42) = 3.56; p <
      .01]. The inhibition of sodium-independent [3H]glutamate binding occurred in the
      absence of Mg2+. These findings suggest that guanine nucleotides may inhibit
      glutamate binding and activate adenylate cyclase through distinct mechanisms by
      acting on different sites.

PMID- 9016845
TI  - Characterization of melittin effects in synaptosomes.
AB  - The effects of melittin at increasing concentrations on: [3H]GABA release from
      mouse brain synaptosomes; on the radioactivity released from [3H]arachidonic acid
      labeled synaptosomal membranes; on synaptosomes ultrastructure and on the leakage
      of the cytoplasmic marker, lactate-dehydrogenase (LDH) was investigated. Melittin
      0.3, 1, 3, 7, and 10 microM progressively increases [3H]GABA release, but the
      efficacy of melittin is decreased when the amount of tissue exposed to a constant
      concentration of the toxin increases. The release of [3H]GABA induced by melittin
      below 3 microM is Ca2+ dependent, but not that induced by the higher
      concentrations. The Ca2+ dependent fraction of the [3H]GABA released by 0.3
      microM melittin is selectively inhibited by 10 microM quinacrine and 1 microM
      nordihydroguaiaretic acid (NDGA) and facilitated by 3 microM indomethacin,
      whereas the Ca2+ independent fraction of the [3H]GABA released by melittin is
      not. In the presence of Ca2+, melittin 0.3, 1 and 10 microM progressively
      increases [3H]arachidonic acid release over control release, but the
      effectiveness of melittin is also decreased as the amount of tissue increases. No
      apparent changes in synaptosomes ultrastructure are observed in 0.3 microM
      treated synaptosomes, but a noticeable disorganization is produced in 10 microM
      melittin-treated synaptosomes, independently on the presence of external Ca2+.
      LDH activity only increases over control activity in the supernatant solutions of
      10 microM melittin treated synaptosomes, also in a Ca2+ independent manner. Our
      interpretation of these results is that the Ca2+-dependent, pharmacologic
      sensitive component of melittin-induced release of [3H]GABA, unmasked when 0.3
      microM melittin was used, involves the activation of a Ca2+-dependent type of
      membrane PLA2. The Ca2+-independent release of [3H]GABA is in contrast, highly
      probable to be due to the membrane perturbation produced by complex
      melittin/lipid interactions.

PMID- 9016846
TI  - Lipid peroxides are generated by the fetal rat brain after episodes of global
      ischemia in utero.
AB  - Complete arrest of maternal-fetal blood supply for up to 30 min caused a time
      dependent increase in the endogenous levels of lipid peroxides (LPO) in fetal
      brain and liver extracts and fetal blood and amniotic fluids as indicated by the
      appearance of thiobarbituric acid reactive substances (TBARS). A steady increase
      of TBARS from 48.0 +/- 2.2 pmol/g wet weight to 75.0 +/- 5.6 pmol/g wet weight up
      to 30 min restriction was noticed in the fetal brain. The fetal liver TBARS
      values increased by approximately 69% after 5 min restriction and remained high,
      above the control level, for 30 min. After two days reperfusion following 30 min
      restriction, the TBARS levels in the fetal brain were 1.8 fold higher above the
      control, while those of the liver returned to control values. The levels of the
      lipid-soluble antioxidant alpha-tocopherol were reduced by about 40% and 50% in
      the placenta and brain tissues after 5 min restriction, respectively. Slices of
      fetal brain incubated at 37 degrees C in DMEM under oxygen in the presence of 50
      microM Fe2+ were able to generate LPO in a time- and tissue concentration
      dependent manner. After 15 min incubation, about 6.3 fold increase in total TBARS
      levels could be measured in the presence of 50 microM Fe2+, most of which was
      released in the medium. The iron chelator desferrioxamine (25 microM) and the
      antioxidant alpha-tocopherol (10 microM) added to the incubation medium, each
      inhibited by about 88% TBARS production. After 20 min episode of ischemia, fetal
      brain slices released into the medium 138.5 +/- 9.8 nmol/15 min/mg DNA compared
      to 75.9 +/- 4.5 nmol/15 min/mg DNA released by the sham preparations. After 3 h
      reperfusion, brain slices from fetuses exposed to 20 min ischemia continued to
      produce TBARS above control levels, whereas those of brief ischemia (5 min)
      returned to control levels. The data indicate that the limited resistance of the
      fetal brain to brief, rather than prolonged, periods of ischemia, is likely due
      to a lack of free FA for LPO generation, rather than the levels of tissue lipid
      antioxidants.

PMID- 9016847
TI  - Immunocytochemical detection of anti-hippocampal antibodies in Alzheimer's
      disease and normal cerebrospinal fluid.
AB  - Immunocytochemical staining was performed to investigate the presence of anti
      hippocampal antibodies in cerebrospinal fluid (CSF) from patients with probable
      Alzheimer's disease (AD) (n = 19), aged normal controls (n = 9), and young normal
      controls (n = 10). Marked staining of neurons in the granule cell layer of the
      dentate gyrus and in pyramidal neurons in CA1-3 of the rat hippocampus was
      observed in 5 AD CSF samples (26%), 1 aged control sample (11%), and 1 young
      control sample (10%). These differences were not statistically significant. One
      of the immunoreactive AD CSF specimens also contained high concentrations of C5b
      9, the membrane attack complex. The infrequent occurrence of anti-hippocampal
      antibodies in AD CSF, and the detection of similar immunoreactivity in control
      CSF specimens, suggest that these antibodies are unlikely to play a role in the
      neurodegenerative process in most individuals with AD. However, elevated C5b-9
      concentration in an AD CSF specimen with marked immunoreactivity to hippocampal
      neurons suggests the possibility that anti-neuronal antibodies may contribute to
      complement activation in some AD patients.

PMID- 9016848
TI  - Kinetics of K(+)-p-nitrophenyl phosphatase stimulation by a brain soluble
      fraction.
AB  - We have already described the separation of two brain soluble fractions by
      Sephadex G-50, one of which stimulates (peak I) and the other inhibits (peak II)
      Na+, K(+)-ATPase and K(+)-p-nitrophenylphosphatase (K(+)-p-NPPase) activities.
      Here we examine the features of synaptosomal membrane p-NPPase activity in the
      presence and absence of brain peak I. It was observed that stimulation of Mg2+,
      K(+)-p-NPPase activity by peak I was concentration dependent. The ability of peak
      I to stimulate p-NPPase activity was lost by heat treatment followed by brief
      centrifugation. Pure serum albumin also stimulated enzyme activity. K(+)-p-NPPase
      stimulation by peak I proved dependent on K+ concentration but independent of
      Mg2+ and substrate p-nitrophenylphosphate concentrations. Since our
      determinations were performed in a non-phosphorylating condition reflecting the
      Na+, K(+)-ATPase Na+ site, it is suggested that peak I may stimulate the Na+
      dependent enzyme phosphorylation known to take place from the internal
      cytoplasmic side.

PMID- 9016849
TI  - Epipregnanolone acts as a partial agonist on a common neurosteroid modulatory
      site of the GABA(A) receptor complex in avian CNS.
AB  - Neurosteroid modulatory sites present in the GABA(A) receptor complex in chick
      optic lobe were investigated, in order to evaluate whether allopregnanolone and
      alphaxalone act through a common site of action. Results showed that either
      allopregnanolone or alphaxalone present a single-component enhancement of
      [3H]flunitrazepam binding with EC50 of 1.18 +/- 0.12 and 6.56 +/- 0.86 microM and
      Emax of 82.18 +/- 5.80 and 62.98 +/- 3.73%, respectively. Epipregnanolone behaved
      as a partial agonist of these steroid modulatory sites with EC50 of 0.49 +/- 0.15
      microM and Emax 12.34 +/- 1.03%. Moreover, the addition of 16 microM
      epipregnanolone to either allopregnanolone or alphaxalone decreased EC50 values
      to 0.54 +/- 0.09 and 1.24 +/- 0.25 microM respectively, while Emax values were
      not significantly affected. On the other hand, additivity experiments disclosed
      that a maximal concentration (16 microM) of alphaxalone in the presence of
      allopregnanolone failed to enhance [3H]flunitrazepam binding in excess of that
      produced by allopregnanolone alone. Results indicate that not only
      allopregnanolone and alphaxalone act through a common site of action, but such
      site is highly stereospecific with regard to the neurosteroid spatial
      configuration.

PMID- 9016850
TI  - Media from rhabdomyosarcoma and neuroblastoma cell cultures stimulate in vitro
      aggregation and fibrillization of amyloid beta-protein.
AB  - In vitro aggregation and fibrillization of synthetic amyloid beta-protein Abeta 1
      40 was assessed in the conditioned media from rhabdomyosarcoma (CRL 1598, HTB 82,
      HTB 153, CCL 136), adenocarcinoma (CCL 218), neuroblastoma (SY5Y), and COS cells
      cultured in the absence and presence of 10% heat-inactivated fetal bovine serum
      (FBS). The aggregation and formation of cross beta-pleated sheet structures in
      Abeta was quantitated by Thioflavin T (ThT) fluorescence spectroscopy, while the
      morphology of Abeta fibrils was examined in negative staining in the
      electronmicroscope (EM). In cultures supplemented with 10% FBS, the conditioned
      media from CRL 1598, HTB 82, CCL 218, and SY5Y cell cultures stimulated Abeta
      aggregation in a time-dependent manner as compared to that of control (serum
      containing medium that had not been exposed to cells). The order of stimulation
      was SY5Y > CRL 1598 > or = HTB 82 > CCL 218, and the stimulation was higher in 2
      week cultures than in 1 week cultures. Similar studies using media from HTB 153,
      CCL 136 and COS cell cultures showed no effect on Abeta 1-40 aggregation. In
      serum-free cell cultures, only media from SY5Y and CRL 1598 could promote
      significant aggregation of Abeta 1-40. Negative staining in EM revealed Abeta
      fibril formation only with conditioned media from SY5Y and CRL 1598 cultured
      under serum free conditions; no Abeta fibrils were noticed in media from cell
      cultures supplemented with 10% FBS. We propose that both the SY5Y neuroblastoma
      cell line and the CRL 1598 rhabdomyosarcoma cell line may serve as experimental
      models for in vitro studies of extracellular aggregation and fibrillization of
      Abeta-protein in cell cultures, while rhabdomyosarcoma HTB 82 and adenocarcinoma
      CCL 218 may be models for study of Abeta aggregation only.

PMID- 9016851
TI  - Time to get down and dirty in defining misconduct.

PMID- 9016852
TI  - Fetal proteins in uremia: a metabolic encore?

PMID- 9016853
TI  - Adaptation to changes in dietary phosphorus intake in health and in renal
      failure.
AB  - Phosphate (Pi) homeostasis is maintained by the ability of the kidneys to adjust
      the tubular reabsorption of Pi to changes in the dietary intake of phosphorus.
      Renal tubular Pi reabsorption increases with the ingestion of a low-phosphorus
      diet (LPD) and decreases when a high-phosphorus diet (HPD) is consumed. A similar
      adaptive mechanism is also operative at the intestinal microvillus. The adaptive
      changes in Pi reabsorption are independent of parathyroid hormone production and
      are paralleled by similar changes in the Na+-dependent Pi transport at the brush
      border membrane (BBM). Type II Na+-Pi cotransporters (NaPi-2) are mainly involved
      in such regulatory mechanisms. Chronic dietary phosphorus restriction leads to
      increased Na+-Pi cotransport rate, along with increased NaPi-2 protein and mRNA
      abundance. In acute dietary phosphorus restriction, transport rate and NaPi-2
      protein are also increased, but mRNA abundance remains unchanged. A shuttling
      mechanism involving translocation of cotransporters from intracellular pools to
      the BBM is involved in the rapid proximal tubular adaptation. The intestinal
      adaptation to changes in dietary phosphorus are similar to those described for
      the renal Pi transport, but the molecular structure of the intestinal Na+-Pi
      cotransporter is not known. When nephron mass is reduced, phosphate homeostasis
      is maintained through enhanced Pi excretion by residual nephrons. The adaptation
      to renal mass reduction is mediated by increased parathyroid hormone (PTH)
      production and by PTH-independent mechanisms, including increased intrarenal
      dopamine production. The adaptive changes of Pi transport to dietary phosphorus
      restriction can counteract the effect of dietary phosphorus reduction often
      prescribed in patients with renal failure. However, because of the reduced
      filtered load of Pi, the overall impact on serum Pi concentration is minimal.

PMID- 9016854
TI  - Truth, fairness, and the definition of scientific misconduct.

PMID- 9016855
TI  - Fetal proteins and chronic treatment with low-dose erythropoietin.
AB  - The potential stimulating effect of erythropoietin on the production of fetal
      proteins (FPs) has not been explored in human subjects. Therefore, the plasma
      levels of fetal fibrinogen (FF), carcinoembriogenic antigen (CEA), alpha
      fetoprotein (AFP), and fetal hemoglobin (HbF) were measured in 12 uremic
      hemodialyzed patients before the first administration and after 1, 2, and 3
      months of low-dose erythropoietin (r-Hu-EPO; 45 U/kg body wt I.V., thrice
      weekly). Such a treatment efficaciously increased total hemoglobin (Hb). CEA and
      AFP increased from 5.8 +/- 1.1 ng/ml and 2.9 +/- 0.9 ng/ml to the final value of
      43.2 +/- 3.9 ng/ml and 8.7 +/- 1.1 ng/ml, respectively, in the absence of
      detectable neoplastic diseases. The levels of FF did not change. HbF levels
      increased from <3% of Hb to the peak value of 48% at the end of the first month;
      subsequently, a progressive reduction in HbF was observed. Similar changes were
      detected in the reticulocyte count (RET). A striking correlation was found
      between HbF and RET (r = 0.8633, p < 0.0001), indicating that the increment in
      HbF was dependent on the erythroid activity. In conclusion, this study evidences
      broader than expected effects of erythropoietin on the synthesis of FP and
      suggests that (1) r-Hu-EPO markedly increases HbF in a condition of suppressed
      bone marrow activity, (2) the measurement of the cell proliferation markers CEA
      and AFP is unreliable during r-Hu-EPO therapy, and (3) the prothrombotic state
      associated with chronic r-Hu-EPO treatment in patients with uremia cannot be
      attributed to the presence of FF.

PMID- 9016856
TI  - Early morphologic changes of atherosclerosis induced by ventromedial hypothalamic
      lesion in the spontaneously diabetic Goto-Kakizaki rat.
AB  - It is generally thought that typical atherosclerotic lesions do not develop in
      the rodent. The Goto-Kakizaki (GK) rat is a nonobese strain in which a
      spontaneous type of non-insulin-dependent diabetes mellitus develops without
      apparent macroangiopathy. In our previous study, making ventromedial hypothalamic
      (VMH) lesions in GK rats induced hyperphagia and a further deterioration in
      glucose metabolism. In the current study, male GK rats in which VMH lesions were
      made were examined for vascular changes, with special reference to
      atherosclerotic lesions. Marked hyperglycemia in GK rats with VMH lesions
      (hereafter referred to as VMH lesion rats) was revealed over an observation
      period (plasma glucose levels 16 weeks after the operation: VMH lesion GK rats,
      19.3 +/- 2.0 mmol/L, vs sham-operated GK rats, 10.1 +/- 1.3 mmol/L; p < 0.0001).
      Light microscopic observation of the descending aorta in VMH lesion GK rats 16
      weeks after the surgery revealed that the intimal thickening and the number of
      infiltrating cells into the intima were significantly increased as compared with
      sham-operated GK rats (17531 +/- 3747 microm2 vs 3072 +/- 1192 microm2, p <
      0.0001; 15.6 +/- 3.1 per one transverse section vs 6.8 +/- 2.5 per one transverse
      section, p < 0.0005). Electron microscopic observations demonstrated an increased
      number of microvilli and lysosomes in endothelial cells, infiltration of
      macrophages and lymphocytes into the intima, and migration of medial smooth
      muscle cells into the intima that are considered to be early events in
      atherosclerosis. These morphologic changes could be induced by a deterioration in
      glucose metabolism. This rat may thus be useful for studying the process of the
      initiation of atherosclerosis in diabetes mellitus.

PMID- 9016857
TI  - Endothelial cell mitogenesis induced by LPA: inhibition by thrombospondin-1 and
      thrombospondin-2.
AB  - We examined the effects of thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2) on
      the uptake of tritiated thymidine by bovine aortic endothelial (BAE) cells in
      response to two growth factors, basic fibroblast growth factor (bFGF) and
      lysophosphatidic acid (LPA). bFGF and LPA stimulate cell proliferation through
      distinct receptors that have convergent signaling pathways. The doses of LPA that
      trigger proliferation of BAE cells, which have not been reported previously, were
      1 to 30 micromol/L, as opposed to the 5 to 100 micromol/L concentrations required
      to stimulate proliferation of human foreskin fibroblasts. Baseline mitogenic
      activity and activity stimulated by either bFGF or LPA on BAE cells was inhibited
      by human TSP1 purified from platelets or a recombinant source with a similar dose
      response. These results demonstrate that the anti-proliferative effect of
      platelet TSP1 is not caused by contaminants from the stimulated platelet.
      Recombinant mouse TSP2 inhibited BAE cell proliferation in response to LPA in a
      dose range similar to that of TSP1. Inasmuch as TSP2 does not activate latent
      TGFbeta1 (Schultz-Cherry et al., J Biol Chem 1995;270: 7304), these results show
      that inhibition of angiogenesis by TSPs is not related to control of activation
      of TGFbeta. Together, these studies suggest that structural motifs common to TSP1
      and TSP2 inhibit endothelial cell proliferation. Furthermore, TSPs inhibit cell
      proliferation stimulated by two growth factor receptors that act through distinct
      signaling pathways.

PMID- 9016858
TI  - Differential glycosylation of Bence Jones protein and kidney impairment in
      patients with plasma cell dyscrasia.
AB  - Although Bence Jones protein (BJP) is generally accepted to be critically
      involved in the pathogenic process of kidney impairment in patients with myeloma,
      patients with BJP do not always have kidney dysfunction. As proteins often
      undergo glycosylation and alter their molecular nature, it is expected that the
      heterogeneity in kidney dysfunction can be explained at least partly by the
      differential affinity to the kidneys of BJP dependent on its glycosylation.
      Accordingly, we analyzed the structures of carbohydrates of urine BJP
      biochemically to correlate the structure with kidney function. BJP was obtained
      from 16 patients with myeloma, 2 patients with light chain amyloidosis, a patient
      with plasma cell leukemia, and a patient with Waldenstrom's macroglobulinemia.
      All BJP had five forms of oligosaccharides: three forms of biantennary
      oligosaccharides and two forms of triantennaries. The three biantennaries
      correspond to previously reported oligosaccharides on only lambda-type BJP,
      whereas the triantennaries are novel oligosaccharides found on BJP. Among the
      five oligosaccharides, the triantennary oligosaccharide Gal(beta)1-4GlcNAc(beta)1
      2Man(alpha)1-6 [Gal(beta)1-GlcNA(beta)1-4(Gal(beta)1-4GlcNAc(beta) 1
      2)Man(alpha)1-3]Man(beta)1-4GlcNAc(beta)1-4GlcNAc showed a significant negative
      correlation with the serum creatinine level (p = 0.015 by Spearman's correlation
      test, R = 0.744). Thus determination of BJP glycosylation may be useful for the
      evaluation of kidney impairment in patients with BJP.

PMID- 9016859
TI  - Oxidized low-density lipoprotein stimulates endothelin-1 release and mRNA
      expression from rat mesangial cells.
AB  - Evidence indicates that the glomerular injuries and renal hemodynamic
      abnormalities in hyperlipidemia are caused by the interaction of low-density
      lipoprotein (LDL) and oxidized LDL (Ox-LDL) with mesangial cells. Experiments
      were designed to investigate whether the synthesis of mesangial cell endothelin-1
      (ET-1), a potent renal vasoconstrictor and mitogen for mesangial cells, is
      modulated by LDL and Ox-LDL. Using competitive semi-quantitative reverse
      transcription polymerase chain reaction (PCR), we report that the expression of
      cultured rat mesangial cell ET-1 mRNA was increased after treatment with Ox-LDL
      but not native LDL. Ox-LDL stimulated the release of ET-1 peptide into the
      culture medium in a time- and concentration-dependent manner. The maximal effect
      was observed at a concentration of 100 microg/ml, and a higher dose of Ox-LDL was
      found to be cytotoxic to the mesangial cells. Our results suggest that ET-1
      released by Ox-LDL stimulation may be an important pathogenetic factor
      contributing to the renal hemodynamic alterations and progressive chronic renal
      diseases induced by hypercholesterolemia.

PMID- 9016860
TI  - Thrombospondin, a negative modulator of megakaryocytopoiesis.
AB  - The effects of native thrombospondin (TSP), an 18 kd recombinant protein
      comprising residues 1-174 of TSP (TSP1-174) with heparin-binding domain and a
      fusion protein comprising residues 559-669 of TSP (TSP559-669) on murine
      hematopoiesis, were studied by using different in vitro culture systems. TSP by
      itself did not show an inhibitory effect on colony-forming unit-megakaryocyte
      (CFU-MK) growth in a serum-free agar system and on the growth of colony-forming
      unit-granulocyte and macrophage (CFU-GM) in a plasma clot system. It was,
      however, found that in the plasma clot culture system when using aplastic anemia
      serum as the source of thrombopoietin or C-Mpl ligand (TPO), TSP and TSP1-174,
      but not TSP559-669, were able to inhibit the growth of CFU-MK from unfractionated
      and lineage negative (Lin-) bone marrow cells in a dose-dependent manner. A
      statistically significant suppression was seen at 1 microg/ml of TSP and 5
      microg/ml of TSP1-174. This inhibitory effect of TSP was further found in both
      the serum-free agar system and the plasma clot system without aplastic anemia
      serum, where megakaryocyte colony growth was stimulated by recombinant TPO, basic
      fibroblast growth factor (bFGF), or interleukin-3 (IL-3). In a methylcellulose
      system, where a combination of stem cell factor (SCF), IL-3, and
      granulocyte/macrophage colony-stimulating factor (GM-CSF) were used, TSP
      inhibited the growth of colony-forming unit-granulocyte-erythroblast,
      megakaryocyte, and macrophage (CFU-GEMM) but not CFU-GM and burst-forming unit
      erythroblast (BFU-E). Interestingly, this inhibitory effect of TSP on
      megakaryocyte colony growth could be counteracted by Fraxiparin, a low-molecular
      weight heparin. These results demonstrate that TSP is a negative modulator of
      megakaryocytopoiesis and suggest that its inhibitory effect is at least partially
      mediated by N-terminal heparin-binding domain.

PMID- 9016861
TI  - Expression of monocyte chemoattractant protein-1 in experimental crescentic
      glomerulonephritis in rats.
AB  - Crescentic glomerulonephritis (CGN) is a rapidly progressive glomerular disease
      that is usually associated with a poor prognosis. Monocytes/macrophages are
      frequently observed in glomeruli in cases of CGN, and they are considered to play
      a crucial role in the pathogenesis of this disease. In this study we analyzed the
      glomerular expression of monocyte chemoattractant protein-1 (MCP-1), a potent
      chemoattractant for monocytes, in an experimental model of CGN. A model of the
      disease was induced in the WKY strain of rats by intravenous injection of
      antiserum raised against glomerular basement membranes. Accumulation of
      monocytes/macrophages in glomeruli was observed 4 hours after the injection of
      antiserum. Northern blot analysis showed that the expression of mRNA for MCP-1
      was enhanced within 4 hours, peaked on day 3--when it was 60 times that in the
      control--and then declined. Immunostaining with MCP-1-specific antibody revealed
      the expression of MCP-1 protein in the diseased glomeruli but not in control
      glomeruli. Quantitative analysis of glomerular MCP-1 protein by enzyme-linked
      immunosorbent assay revealed a level 46 times that in the control in reflecting
      the increase in mRNA for MCP-1. These results indicate that glomeruli of rats
      with CGN produce MCP-1, which may play an important role in the pathogenesis of
      glomerular inflammation and crescent formation in CGN.

PMID- 9016862
TI  - Altered intracellular calcium and phorbol 12,13-dibutyrate binding to intact
      platelets in young obese subjects.
AB  - The study was designed to examine cytosolic free calcium ((Ca2+)i) and phorbol
      dibutyryl ester binding in intact platelets of young obese subjects as compared
      with the platelets of age-matched subjects with non-insulin-dependent diabetes
      mellitus (NIDDM) and those of healthy control subjects. The assay was studied in
      basal and thrombin-stimulated conditions. The binding parameter of phorbol ester
      is a criterion for active protein kinase C (PKC) units in the platelet plasma
      membrane. The resting (Ca2+)i correlated with body mass index (BMI)(r = 0.385, p
      = 0.0034) and plasma insulin level (r = 0.316, p = 0.0269), and the resting
      (Ca2+)i level was higher in the obesity group (160.6 +/- 15.8 nmol/L; n = 25)
      than controls (78.9 +/- 7.6 nmol/L; n = 24, p < 0.0001). Among the obesity and
      control groups, there was a correlation between BMI and fasting plasma insulin
      level (r = 0.399, p = 0.0237). Systolic blood pressure correlated with BMI(r =
      0.504, p = 0.0005). The mean systolic blood pressure of the obesity group was
      higher than those of the other two groups. The mean Hill coefficient for thrombin
      treated platelets of phorbol dibutyrate binding was higher in the obesity group
      when compared with healthy controls and the subjects with NIDDM (1.47 +/- 0.21 vs
      1.06 +/- 0.16 and 0.99 +/- 0.09, respectively; p < 0.05). In conclusion, young
      subjects with simple obesity have already developed altered platelet Ca2+
      regulation that is usually observed in adult patients with a number of metabolic
      diseases. These data are interpreted to indicate that a relationship exists
      between dysregulation of PKC and impaired glucose tolerance that precedes other
      complications of obesity.

PMID- 9016865
TI  - Complementary medicine: a different dimension.

PMID- 9016863
TI  - Abnormal collagen binding activity of 2A von Willebrand factor: evidence that the
      defect depends only on the lack of large multimers.
AB  - It is well established that the large von Willebrand factor (vWf) multimers bind
      with high affinity to the extracellular matrix. To explore the different roles of
      intermediate and large vWf multimers, we studied the collagen-binding activity
      (vWf:CBA) of 2A vWf under nonflowing conditions in relation to the multimer
      organization of the molecule. Regardless of the anticoagulant used for blood
      collection, vWf:CBA was significantly decreased, in 4 patients with 2A von
      Willebrand's disease (vWd), in accordance with the lack of high and intermediate
      vWf multimers. After 1-deamino-8-D-arginine vasopressin (DDAVP) infusion, the
      appearance of circulating large and unusually large vWf multimers, in samples
      collected in the presence of protease inhibitors, induced a complete
      normalization of vWf:CBA. The peak was observed 15 minutes after DDAVP, when
      large and unusually large multimers were maximally represented. These effects
      were transient because vWf:CBA decreased after 60 minutes, even though values
      were still significantly higher than pre-DDAVP figures; at the same time, large
      vWf multimers appeared to be decreased. In contrast, samples anticoagulated with
      sodium citrate after DDAVP did not show a normalized vWf multimer pattern and
      were characterized by a persistently decreased vWf:CBA. Moreover, in all of the
      patients studied, platelet vWf presented normal vWf:CBA values in accordance with
      the normal levels and multimer organization of the vWf molecule. Our findings
      indicate that the collagen-binding defect displayed in vitro by type 2A vWf
      depends only on the lack of circulating large vWf multimers. Moreover, the
      observation of normal platelet vWf:CBA seems to indicate a primary role of plasma
      rather than platelet vWf in assuring platelet plug formation.

PMID- 9016864
TI  - Fatty acid-induced cytotoxicity: differences in susceptibility between MDCK cells
      and primary cultures of proximal tubular cells.
AB  - We have compared the cytotoxicity of exogenously added fatty acid (oleic acid)
      and that of endogenous free fatty acids released from cell membranes by
      phospholipase A2 in primary cultures of mouse proximal tubular (MPT) cells and in
      Madine-Darby canine kidney (MDCK) cells. Exposure of MPT cell monolayers to oleic
      acid (125 mmol/L) for 2 hours resulted in severe irreversible injury to 70% +/-
      4% of MPT cells. In striking contrast, only 8% +/- 3% of MDCK cells were killed
      by the same insult. This striking difference in the response to exogenous oleate
      by MPT and MDCK cells was associated with modest and comparable reductions in
      cell adenosine triphosphate (ATP) content in both cell types. Chemical anoxia
      induced by cyanide plus deoxyglucose (CN-DOG) in the absence of glucose was
      associated with greater injury in MPT cells (45% +/- 6% killed) than in MDCK
      cells (16% +/- 5% cells killed) despite severe and comparable depletion of cell
      ATP content in both MPT cells (96.0% +/- 0.6% reduction) and MDCK cells (96.0% +/
      0.5% reduction). The release of endogenous fatty acids by the exposure of cells
      to exogenous phospholipase A2 caused mild injury in both cell types that was more
      severe in MPT cells than in MDCK cells. The combined insult of phospholipase A2
      and chemical anoxia for 2 hours caused substantially greater cell injury in both
      MPT and MDCK cells than either intervention alone, but the combined insult was
      still more damaging to MPT cells (73% +/- 4% killed) than to MDCK cells (30% +/-
      4% killed). We conclude that the cell membrane in MDCK cells is intrinsically
      more resistant to fatty acid-induced injury than the lipid membrane in MPT cells.

PMID- 9016866
TI  - Heparin, beta2-glycoprotein I, and thrombocytopenia.

PMID- 9016867
TI  - The promotion of V region hypermutation.

PMID- 9016868
TI  - The common cytokine receptor gamma chain plays an essential role in regulating
      lymphoid homeostasis.
AB  - In the immune system, there is a careful regulation not only of lymphoid
      development and proliferation, but also of the fate of activated and
      proliferating cells. Although the manner in which these diverse events are
      coordinated is incompletely understood, cytokines are known to play major roles.
      Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for
      lymphocyte proliferation. The receptors for each of these cytokines contain the
      common cytokine receptor gamma chain (gammac), and it was previously shown that
      gammac-deficient mice exhibit severely compromised development and responsiveness
      to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent
      accumulation of splenic CD4+ T cells, the majority of which have a phenotype
      typical of memory/activated cells. When gammac-deficient mice were mated to
      DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing
      endogenous TCRs had this phenotype, suggesting that its acquisition was TCR
      dependent. Not only do the CD4+ T cells from gammac-deficient mice exhibit an
      activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but,
      consistent with the lack of gammac-dependent survival signals, they also exhibit
      an augmented rate of apoptosis. However, because the CD4+ T cells accumulate, it
      is clear that the rate of proliferation exceeds the rate of cell death. Thus,
      surprisingly, although gammac-independent signals are sufficient to mediate
      expansion of CD4+ T cells in these mice, gammac-dependent signals are required to
      regulate the fate of activated CD4+ T cells, underscoring the importance of
      gammac-dependent signals in controlling lymphoid homeo-stasis.

PMID- 9016869
TI  - Peripheral expression of Jak3 is required to maintain T lymphocyte function.
AB  - The Jak family tyrosine kinase, Jak3, is involved in signaling through cytokine
      receptors that utilize the common gamma chain (gammac), such as those for IL-2,
      IL-4, IL-7, IL-9, and IL-15. Recent studies of Jak3-deficient mice and humans
      have demonstrated that Jak3 plays a critical role in B and T lymphocyte
      maturation and function. The T lymphocyte defects in Jak3-deficient mice include
      a small thymus, a decrease in peripheral CD8+ cells, an increase in the surface
      expression of activation markers, and a severe reduction in proliferative and
      cytokine secretion responses to mitogenic stimuli. To determine whether the
      peripheral T lymphocyte defects result from aberrant maturation in the thymus or
      from the absence of Jak3 protein in peripheral T cells, we generated
      reconstituted mice that express normal levels of Jak3 protein in the thymus but
      lose Jak3 expression in peripheral T cells. Jak3 expression in the thymus
      restores normal T cell development, including CD8+, gammadelta, and natural
      killer cells. However, the loss of Jak3 protein in peripheral T cells leads to
      the Jak3-/- phenotype, demonstrating that Jak3 is constitutively required to
      maintain T cell function.

PMID- 9016870
TI  - Absence of respiratory burst in X-linked chronic granulomatous disease mice leads
      to abnormalities in both host defense and inflammatory response to Aspergillus
      fumigatus.
AB  - Mice with X-linked chronic granulomatous disease (CGD) generated by targeted
      disruption of the gp91phox subunit of the NADPH-oxidase complex (X-CGD mice) were
      examined for their response to respiratory challenge with Aspergillus fumigatus.
      This opportunistic fungal pathogen causes infection in CGD patients due to the
      deficient generation of neutrophil respiratory burst oxidants important for
      damaging A. fumigatus hyphae. Alveolar macrophages from X-CGD mice were found to
      kill A. fumigatus conidia in vitro as effectively as alveolar macrophages from
      wild-type mice. Pulmonary disease in X-CGD mice was observed after administration
      of doses ranging from 10(5) to 48 spores, none of which produced disease in wild
      type mice. Higher doses produced a rapidly fatal bronchopneumonia in X-CGD mice,
      whereas progression of disease was slower at lower doses, with development of
      chronic inflammatory lesions. Marked differences were also observed in the
      response of X-CGD mice to the administration of sterilized Aspergillus hyphae
      into the lung. Within 24 hours of administration, X-CGD mice had significantly
      higher numbers of alveolar neutrophils and increased expression of the
      proinflammatory cytokines IL-1 beta and TNF-alpha relative to the responses seen
      in wild-type mice. By one week after administration, pulmonary inflammation was
      resolving in wild-type mice, whereas X-CGD mice developed chronic granulomatous
      lesions that persisted for at least six weeks. This is the first experimental
      evidence that chronic inflammation in CGD does not always result from persistent
      infection, and suggests that the clinical manifestations of this disorder reflect
      both impaired microbial killing as well as other abnormalities in the
      inflammatory response in the absence of a respiratory burst.

PMID- 9016871
TI  - The efficiency of CD4 recruitment to ligand-engaged TCR controls the
      agonist/partial agonist properties of peptide-MHC molecule ligands.
AB  - One hypothesis seeking to explain the signaling and biological properties of T
      cell receptor for antigen (TCR) partial agonists and antagonists is the
      coreceptor density/kinetic model, which proposes that the pharmacologic behavior
      of a TCR ligand is largely determined by the relative rates of (a) dissociation
      ofligand from an engaged TCR and (b) recruitment oflck-linked coreceptors to this
      ligand-engaged receptor. Using several approaches to prevent or reduce the
      association of CD4 with occupied TCR, we demonstrate that consistent with this
      hypothesis, the biological and biochemical consequence of limiting this
      interaction is to convert typical agonists into partial agonist stimuli. Thus,
      adding anti-CD4 antibody to T cells recognizing a wild-type peptide-MHC class II
      ligand leads to disproportionate inhibition of interleukin-2 (IL-2) relative to
      IL-3 production, the same pattern seen using a TCR partial agonist/antagonist. In
      addition, T cells exposed to wild-type ligand in the presence of anti-CD4
      antibodies show a pattern of TCR signaling resembling that seen using partial
      agonists, with predominant accumulation of the p21 tyrosine-phosphorylated form
      of TCR-zeta, reduced tyrosine phosphorylation of CD3epsilon, and no detectable
      phosphorylation of ZAP-70. Similar results are obtained when the wild-type ligand
      is presented by mutant class II MHC molecules unable to bind CD4. Likewise,
      antibody coligation of CD3 and CD4 results in an agonist-like phosphorylation
      pattern, whereas bivalent engagement of CD3 alone gives a partial agonist-like
      pattern. Finally, in accord with data showing that partial agonists often induce
      T cell anergy, CD4 blockade during antigen exposure renders cloned T cells unable
      to produce IL-2 upon restimulation. These results demonstrate that the
      biochemical and functional responses to variant TCR ligands with partial agonist
      properties can be largely reproduced by inhibiting recruitment of CD4 to a TCR
      binding a wild-type ligand, consistent with the idea that the relative rates of
      TCR-ligand disengagement and of association of engaged TCR with CD4 may play a
      key role in determining the pharmacologic properties of peptide-MHC molecule
      ligands. Beyond this insight into signaling through the TCR, these results have
      implications for models of thymocyte selection and the use of anti-coreceptor
      antibodies in vivo for the establishment ofimmunological tolerance.

PMID- 9016872
TI  - Reduced incidence and severity of antigen-induced autoimmune diseases in mice
      lacking interferon regulatory factor-1.
AB  - Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates
      interferon-induced genes and type I interferons. Recently, studies of IRF-l
      deficient mice have revealed that IRF-I regulates the induction of molecules that
      play important roles in inflammation, such as inducible nitric oxide synthase
      (iNOS) and interleukin-l beta-converting enzyme (ICE). To study the role of IRF-1
      in autoimmunity, we investigated type II collagen-induced arthritis (CIA), and
      experimental allergic encephalomyelitis (EAE), in mice lacking IRF-1. The
      incidence and severity of CIA were significantly decreased in IRF-1-/- mice
      compared with IRF-l +/- mice, as was the production of interferon (IFN)-gamma in
      lymph node cells. Both IRF-l+/- and IRF-1-/- mice exhibited mild and transient
      disease after adoptive transfer of a type II collagen (CII)-specific T cell line
      together with sera from arthritic mice, but the IRF-1-/- mice were less severely
      affected than the IRF-1+/- mice. In addition, the incidence of EAE in IRF-1-/-
      mice was decreased as compared with IRF-1 +/- mice. Reverse transcription
      polymerase chain reaction showed that IRF-1 mRNA was constitutively expressed in
      the spinal cords of IRF-1+/- mice, and was upregulated in mice with clinical EAE.
      Expression of iNOS was also detected in inflamed spinal cords. These results
      suggest that IRF-I plays a key role in promoting inflammation and autoimmunity in
      CIA and EAE animal models.

PMID- 9016873
TI  - The transcriptional promoter regulates hypermutation of the antibody heavy chain
      locus.
AB  - A somatic process introduces mutations into antibody variable (V) region genes at
      a high rate in many vertebrates, and is a major source of antibody diversity. The
      mechanism of this hypermutation process remains enigmatic, although retrospective
      studies and transgenic experiments have recently suggested a role for
      transcriptional regulatory elements. Here, we demonstrate that mouse heavy (H)
      chain loci in which the natural VH promoter has been replaced by a heterologous
      promoter undergo hypermutation. However, while the distribution of mutation in
      such loci appears normal, the frequency of mutation does not. Conversely, moving
      the VH promoter 750 bp upstream of its normal location results in a commensurate
      change in the site specificity of hypermutation in H chain loci, and the foreign
      DNA inserted into the VH leader intron to produce this promoter displacement is
      hypermutated in a manner indistinguishable from natural Ig DNA. These data
      establish a direct mechanistic link between the IgH transcription and
      hypermutation processes.

PMID- 9016874
TI  - Distinct costimulatory molecules are required for the induction of effector and
      memory cytotoxic T lymphocytes.
AB  - A successful T cell immune response has two major products: effector T cells
      which directly or indirectly remove the antigens, and memory T cells, which allow
      a faster and more efficient recall response when challenged by related antigens.
      An important issue is whether costimulatory molecules on the antigen-presenting
      cells are involved in determining whether T cells will differentiate into
      effector or memory cells after antigenic stimulation. To address this issue, we
      have produced mice with targeted mutations of either the heat-stable antigen
      (HSA), or both HSA and CD28. We show that CD28/B7 and HSA provide two alternative
      costimulatory pathways for induction of immunological memory to influenza virus.
      Furthermore, our results revealed that B7 is essential for the generation of
      effector T cells from either naive or memory T cells, while HSA is not necessary
      for the generation of effector T cells. Our results demonstrate that the
      induction of memory T cells and effector T cells can utilize distinct
      costimulatory molecules. These results have important implications on lineage
      relationship between effector and memory T cells.

PMID- 9016875
TI  - Negative selection in the thymus includes semimature T cells.
AB  - The thymic medulla plays a key role in negative selection (self-tolerance
      induction) and contains differentiated T cells en route to the extrathymic
      environment. However, being relatively mature, medullary T cells are thought to
      be beyond the stage of tolerance induction. This paradox is resolved by the
      finding that medullary T cells (CD4+8- thymocytes) comprise two distinct subsets.
      Medullary thymocytes expressing a fully mature (HSAlo) phenotype are strongly
      resistant to tolerance induction, whereas cells with a semimature (HSAhi)
      phenotype are tolerance susceptible. These findings suggest that the
      differentiated T cells reaching the medulla from the cortex remain sensitive to
      tolerance induction for a brief period before acquiring a fully mature tolerance
      resistant phenotype. The semimature subset of medullarsy T cells displays unique
      requirements for tolerance induction; depending upon the conditions used,
      tolerizing these cells can involve either a Fas (CD95)-dependent or a Fas
      independent pathway.

PMID- 9016876
TI  - Estrogen protects lenses against cataract induced by transforming growth factor
      beta (TGFbeta).
AB  - Cataract, already a major cause of visual impairment and blindness, is likely to
      become an increasing problem as the world population ages. In a previous study,
      we showed that transforming growth factor-beta (TGFP) induces rat lenses in
      culture to develop opacities and other changes that have many features of human
      subcapsular cataracts. Here we show that estrogen protects against cataract.
      Lenses from female rats are more resistant to TGFbeta-induced cataract than those
      from males. Furthermore, lenses from ovariectomized females show increased
      sensitivity to the damaging effects of TGFbeta and estrogen replacement in vivo,
      or exposure to estrogen in vitro, restores resistance. Sex-dependent and estrogen
      related differences in susceptibility to cataract formation, consistent with a
      protective role for estrogen, have been noted in some epidemiological studies.
      The present study in the rat indicates that estrogen provides protection against
      cataract by countering the damaging effects of TGFbeP. It also adds to an
      increasing body of evidence that hormone replacement therapy protects
      postmenopausal women against various diseases.

PMID- 9016877
TI  - rho, a small GTP-binding protein, is essential for Shigella invasion of
      epithelial cells.
AB  - Shigella, the causative agents of bacillary dysentery, are capable of invading
      mammalian cells that are not normally phagocytic. Uptake of bacteria by the
      mammalian cells is directed by bacterial factors named IpaB, IpaC, and IpaD
      invasins, in which Ipa invasins secreted into the bacterial environment can
      interact with alpha5beta1 integrin. We report here that Shigella invasion of
      epithelial cells requires rho activity, a ras-related GTP-binding protein. The
      invasive capacity of Shigella flexneri for Chinese hamister ovary (CHO) cells and
      other epithelial cells were greatly reduced when treated with Clostridium
      botulinum exoenzyme C3 transferase. Conversely, uptake of bacteria by CHO cells
      was promoted upon microinjection of an activated rho variant, Val14RhoA.
      Attachment of S. flexneri to CHO cells can elicit tyrosine phosphorylation of
      pp125FAK and paxillin, localized accumulation of F-actin, vinculin, and talin,
      and activation of protein kinase C, which were all blocked by the treatment with
      C3 transferase. Our results indicate that cellular signal transduction regulated
      by rho is essential for Shigella invasion of epithelial cells.

PMID- 9016878
TI  - HIV-1 induces cytotoxic T lymphocytes in the cervix of infected women.
AB  - Although T lymphocytes are present in the genital mucosa, their function in
      sexually transmitted diseases is unproven. To determine if cervical T cells
      mediate HIV-specific cytolysis, mononuclear cells in cytobrush specimens from HIV
      1-infected women were stimulated in vitro with antigen. Resultant cell lines
      lysed autologous targets expressing HIV-1 proteins in 12/19 (63%) subjects, and
      these responses were detected intermittently on repeated visits. All 8 subjects
      with blood CD4+ counts > or =500 cells/microl had HIV-1-specific cervical CTL,
      whereas only 4/11 with counts <500 cells/microl had detectable responses (P =
      0.008). Class II MHC-restricted CD4+ CTL clones lysed targets expressing Env gp41
      or infected with HIV-1. Class I MHC-restricted CD8+ clones recognized HIV-1 Gag-
      or Pol-expressing targets, and the epitopes were mapped to within 9-20 amino
      acids. Comparisons of intra-individual cervical and blood CTL specificities
      indicate that epitopes recognized by CTL in the cervix were commonly recognized
      in the blood. These studies provide the first definitive evidence for an MHC
      restricted effector function in human cervical lymphocytes.

PMID- 9016879
TI  - Major histocompatibility complex (MHC) class I gene expression in single neurons
      of the central nervous system: differential regulation by interferon (IFN)-gamma
      and tumor necrosis factor (TNF)-alpha.
AB  - This study examined the effect of the pro-inflammatory cytokines interferon-gamma
      (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on the induction of MHC
      class I-related genes in functionally mature brain neurons derived from cultures
      of dissociated rat hippocampal tissue. Patch clamp electrophysiology combined
      with single cell RT-PCR demonstrated that approximately 50% of the untreated
      neurons contained mRNA for MHC class I heavy chains, while, with few exceptions,
      the cells failed to transcribe beta2-microglobulin and TAP1/TAP2 gene
      transcripts. No constitutive expression of MHC class I protein was detectable by
      confocal laser microscopy on the surface of neurons. All neurons transcribed the
      alpha-chain of the interferon-type II receptor (binding IFN-gamma) along with the
      p55 receptor for TNF-alpha. Sustained exposure to IFN-gamma resulted in
      transcription of beta2-microglobulin and TAP1/TAP2 genes and MHC class I surface
      expression in a minor part of the neurons, but did not alter their
      electrophysiological activities as assessed by whole cell electrophysiology.
      Suppression of neuronal electric activity by the sodium channel blocker
      tetrodotoxin drastically increased to almost 100% IFN-gamma-mediated induction of
      MHC class I chains, of both TAP transporters, and of membrane expression of MHC
      class I protein. The effect of tetrodotoxin is at least partly reverted by the
      neurotransmitter glutamate. In contrast to IFN-gamma, treatment with TNF-alpha
      did neither upregulate TAP1/TAP2 nor beta2-microglobulin gene expression, but
      induced MHC class I heavy chain gene transcription in all neurons. Consequently,
      no MHC class I molecules were detectable on the membranes of TNF-alpha-treated
      neurons.

PMID- 9016880
TI  - Maturation stages of mouse dendritic cells in growth factor-dependent long-term
      cultures.
AB  - The signals controlling the checkpoints of dendritic cells (DC) maturation and
      the correlation between phenotypical and functional maturational stages were
      investigated in a defined model system of growth factor-dependent immature mouse
      DC. Three sequential stages of DC maturation (immature, mature, and apoptotic)
      were defined and characterized. Immature DC (stage 1) had low expression of
      costimulatory molecules, highly organized cytoskeleton, focal adhesion plaques,
      and slow motility; accordingly, they were very efficient in antigen uptake and
      processing of soluble proteins. Further, at this stage most of major
      histocompatibility complex class II molecules were within cytoplasmic
      compartments consistent with a poor allostimulatory capacity. Bacteria or
      cytokines were very efficient in inducing progression from stage 1 towards stage
      2 (mature). Morphological changes were observed by confocal analysis including
      depolymerization of F-actin and loss of vinculin containing adhesive structures
      which correlates with acquisition of high motility. Antigen uptake and
      presentation of native protein antigen was reduced. In contrast, presentation of
      immunogenic peptides and allostimulatory activity became very efficient and
      secretion of IL-12 p75 was detectable after antigen presentation. This functional
      DC maturation ended by apoptotic cell death, and no reversion to the immature
      phenotype was observed.

PMID- 9016881
TI  - Constitutive expression of interleukin (IL)-4 in vivo causes autoimmune-type
      disorders in mice.
AB  - The transgenic (tg) expression of interleukin (IL)-4 under the control of a major
      histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity
      in mice, characterized by increased B cell surface MHC class II and CD23
      expression, elevated responsiveness of the B cells to polyclonal ex vivo
      stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels. Tg mice
      develop anemia, glomerulonephritis with complement and immune deposition in the
      glomeruli, and show increased production of autoantibodies. Treatment of IL-4 tg
      mice with anti-IL-4 neutralizing antibodies protected the mice from disease
      development, showing that IL-4 was responsible for the observed disorders.
      Deletion of superantigen responsive autoreactive T cells in the IL-4 tg mice was
      normal and treatment of mutant mice with deleting anti-CD4 antibodies failed to
      ablate the onset of autoimmune-like disease, suggesting that CD4+ T cells were
      not the primary cause of the disorders. Furthermore, the deletion of B cells
      reacting against MHC class I molecules was also normal in the IL-4 tg mice.
      Therefore the most likely explanation for the increased production of
      autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on
      autoreactive B cells by expanding them in a polyclonal manner. Taken together our
      results show that inappropriate multi-organ expression of IL-4 in vivo leads to
      autoimmune-type disease in mice.

PMID- 9016882
TI  - CD40 ligation on human cord blood CD34+ hematopoietic progenitors induces their
      proliferation and differentiation into functional dendritic cells.
AB  - Human CD34+ multilineage progenitor cells (CD34HPC) from cord blood and bone
      marrow express CD40, a member of the tumor necrosis factor-receptor family
      present on various hematopoietic and nonhematopoietic cells. As hyper-IgM
      patients with mutated CD40 ligand (CD40L) exhibit neutropenia, no B cell memory,
      and altered T cell functions leading to severe infections, we investigated the
      potential role of CD40 on CD34HPC development. CD40-activated cord blood CD34HPC
      were found to proliferate and differentiate independently of
      granulocyte/macrophage colony-stimulating factor, into a cell population with
      prominent dendritic cell (DC) attributes including priming of allogeneic naive T
      cells. DC generated via the CD40 pathway displayed strong major
      histocompatibility complex class II DR but lacked detectable CD1a and CD40
      expression. These features were shared by a dendritic population identified in
      situ in tonsillar T cell areas. Taken together, the present data demonstrate that
      CD40 is functional on CD34HPC and its cross-linking by CD40L+ cells results in
      the generation of DC that may prime immune reactions during antigen-driven
      responses to pathogenic invasion, thus providing a link between hematopoiesis,
      innate, and adaptive immunity.

PMID- 9016883
TI  - Crucial role of Jak3 in negative selection of self-reactive T cells.
AB  - Jak3 mediates growth signals through cytokine receptors such as interleukin-2 (IL
      2), IL-4, and IL-7, and its deficiency results in autosomal recessive SCID in
      mice and humans. In spite of the severely reduced number of lymphocytes in Jak3
      deficient mice, the differentiation profile of thymocytes was normal and mature T
      cells accumulated in the periphery with age. However, we found that self-reactive
      T cells were not deleted in the thymus and the peripheral tissues in Jak3
      deficient mice. All peripheral T cells were in the activation state and thus were
      unable to be activated further, as demonstrated by the failure of eliciting Ca2+
      response upon T cell receptor (TCR) stimulation. From the analysis of TCR
      transgenic Jak3-deficient mice, only self-reactive T cells appeared to be in the
      activated state and anergic. These findings demonstrate a crucial function of
      Jak3 in the negative selection of autoreactive T cells and the maintenance of
      functional peripheral T cells.

PMID- 9016884
TI  - Asynchronous coreceptor downregulation after positive thymic selection: prolonged
      maintenance of the double positive state in CD8 lineage differentiation due to
      sustained biosynthesis of the CD4 coreceptor.
AB  - In several experimental systems analyzing the generation of single positive (SP)
      thymocytes from double positive (DP) thymocytes, CD4 SP cells have been shown to
      appear before CD8 SP cells. This apparent temporal asymmetry in the maturation of
      CD4 SP and CD8 SP thymocytes could either be due to divergent molecular
      differentiation programs of the two T cell lineages, or merely to slower
      degradation kinetics of the CD4 protein. To study this question in unmanipulated
      in vivo differentiation, we developed a four-color flow cytometry protocol which
      identifies a recently activated TCRintCD69pos thymocyte population containing DP
      cells and early CD4 SP cells but no CD8 SP cells. We show that these
      TCRintCD69pos thymocytes represent a transitory stage in the mainstream alphabeta
      T cell lineage. The precursors of the CD8 SP cells are contained in this
      population as incompletely selected DP cells. Moreover, we show that expression
      of both coreceptors in the TCRintCD69pos population depends on transcriptional
      and translational activity, thus excluding differences in turnover rates of the
      CD4 and CD8 proteins as the cause of the asynchrony in differentiation of the CD4
      and CD8 lineages.

PMID- 9016885
TI  - The HCMV gene products US11 and US2 differ in their ability to attack allelic
      forms of murine major histocompatibility complex (MHC) class I heavy chains.
AB  - Human cytomegalovirus downregulates the expression of human class I major
      histocompatibility complex (MHC) molecules by accelerating destruction of newly
      synthesized class I heavy chains. The HCMV genome contains at least two genes,
      US11 and US2, each of which encode a product sufficient for causing the
      dislocation of newly synthesized class I heavy chains from the lumen of the
      endoplasmic reticulum to the cytosol. Based on a comparison of their abilities to
      degrade the murine class I molecules H-2Kb, Kd, Db, Dd, and Ld, the US11 and US2
      gene products have non-identical specificities for class I molecules.
      Specifically, in human astrocytoma cells (U373-MG) transfected with the US11
      gene, the Kb, Db, Dd, and Ld molecules expressed via recombinant vaccinia virus
      are rapidly degraded, whereas in US2-transfected cells, only Db and Dd are
      significantly destabilized. The diversity in HCMV-encoded functions that
      interfere with class I-restricted presentation likely evolved in response to the
      polymorphism of the MHC.

PMID- 9016887
TI  - Atherosclerotic ischemic renal disease.
AB  - Over the past decade, ischemic nephropathy has gained recognition as a distinct
      and treatable clinical entity. Atherosclerotic renal artery stenosis is the
      leading cause of ischemic renal disease. Among the aging population entering
      renal replacement programs, both renal artery and systemic atherosclerosis are
      common. Over recent years, patients with ischemic renal disease are presenting
      later and have diffuse atherosclerosis and other comorbid conditions. Improved
      screening techniques, patient selection, and interventional approaches have
      resulted in better outcomes in most centers. Percutaneous transluminal renal
      angioplasty has emerged as the treatment of choice in some centers for nonostial
      renal artery stenosis. Both percutaneous transluminal renal angioplasty and
      surgical repair have proven beneficial for renal function salvage. Many studies
      have elegantly demonstrated the pathophysiologic consequences of acute ischemia
      to the kidney. The concepts derived from acute studies have served as a
      springboard for considering the adaptive and maladaptive renal responses to
      chronic ischemia.

PMID- 9016886
TI  - HLA class I binding motifs derived from random peptide libraries differ at the
      COOH terminus from those of eluted peptides.
AB  - Recombinant HLA-A2, HLA-B8, or HLA-B53 heavy chain produced in Escherichia coli
      was combined with recombinant beta2-microglobulin (beta2m) and a pool of randomly
      synthesised nonamer peptides. This mixture was allowed to refold to form stable
      major histocompatability complex (MHC) class I complexes, which were then
      purified by gel filtration chromatography. The peptides bound to the MHC class I
      molecules were subsequently eluted and sequenced as a pool. Peptide binding
      motifs for these three MHC class I molecules were derived and compared with
      previously described motifs derived from analysis of naturally processed peptides
      eluted from the surface of cells. This comparison indicated that the peptides
      bound by the recombinant MHC class I molecules showed a similar motif to
      naturally processed and presented peptides, with the exception of the peptide
      COOH terminus. Whereas the motifs derived from naturally processed peptides
      eluted from HLA-A2 and HLA-B8 indicated a strong preference for hydrophobic amino
      acids at the COOH terminus, this preference was not observed in our studies. We
      propose that this difference reflects the effects of processing or transport on
      the peptide repertoire available for binding to MHC class I molecules in vivo.

PMID- 9016888
TI  - Nephromegaly and elevated hepatocyte growth factor in children with biliary
      atresia.
AB  - Nephromegaly, a rarely mentioned but probably common situation, was studied in
      children with biliary atresia. We evaluated the length and the cross-sectional
      diameters of the kidney by ultrasound in 21 children with biliary atresia as well
      as in 50 healthy children. The ages ranged from 1 month to 10 years. Plasma
      hepatocyte growth factor (HGF) was measured in 18 children with biliary atresia
      and also in 18 age- and sex-matched normal controls. There was a significant
      nephromegaly (increase in the renal length and the kidney volume) in children
      with biliary atresia as compared with normal children (P < 0.001 by analysis of
      covariance). Plasma HGF levels were elevated in these patients (2.13 +/- 1.06 v
      0.76 +/- 0.19 ng/mL in controls, P < 0.001) and had a positive correlation with
      the renal size after considering the effect of body height by multiple regression
      analysis (P = 0.0022 for renal length, and P < 0.001 for kidney volume). These
      results confirm the presence of large kidneys in biliary atresia and implicate
      the possible pathogenic role of HGF in such a condition. Nephromegaly in biliary
      atresia may provide a new in vivo model to study the mechanism of renal growth.

PMID- 9016889
TI  - Treatment of lupus nephritis: a meta-analysis of clinical trials.
AB  - The best therapeutic choice in lupus nephritis remains shrouded in a body of
      controversial literature. The purpose of this review was to assess and compare by
      meta-analysis the efficacy of therapeutic agents used in the treatment of lupus
      nephritis using outcomes of end-stage renal disease (ESRD) and total mortality.
      An exhaustive search was performed using MEDLINE (1970 to 1995) and manual search
      of bibliographic notations and nonindexed sources. Twenty prospective controlled
      trials with treatment allocation by random assignment or consecutive enrollment
      were identified using diagnostic evidence of systemic lupus erythematosus based
      on American Rheumatism Association (ARA) criteria and clinical/biopsy evidence of
      lupus nephritis. One trial was excluded, resulting in 19 trials (n = 440) using
      treatment groups of oral prednisone alone, azathioprine with and without
      concomitant prednisone, oral cyclophosphamide with prednisone, azathioprine and
      oral cyclophosphamide with prednisone, and intravenous cyclophosphamide with
      prednisone. Crude risk data was pooled. An adjusted pooled risk was calculated
      using the random effects model of DerSimonian and Laird. Two measures of clinical
      effectiveness were used to compare treatments: absolute risk differences and
      number needed to treat. Analysis was completed between treatment groups as
      follows: oral prednisone compared with all immunosuppressive agents with
      prednisone and all treatment groups compared with one another. When compared with
      oral prednisone alone, immunosuppressive agents used in conjunction with oral
      prednisone were found to be statistically more effective for both total mortality
      and ESRD (absolute risk differences, 13.2% and 12.9%, respectively). When
      treatment groups were compared, intravenous cyclophosphamide in conjunction with
      oral prednisone was found to be statistically more effective than oral prednisone
      alone for both total mortality and ESRD (absolute risk differences, 19.9% and
      16.2%, respectively). The simultaneous use of azathioprine and oral
      cyclophosphamide concomitant with oral prednisone was found to be 16.9% more
      effective than oral prednisone alone in reducing incidence of ESRD. No difference
      was seen in total mortality and data represented only two studies (n = 30). No
      immunosuppressive agent was found to be statistically more effective than another
      for either total mortality or ESRD. Future prospective studies are needed to
      control for numerous variables and renal function changes to provide more
      definitive answers.

PMID- 9016890
TI  - Idiopathic membranous nephropathy in the elderly: a comparative study.
AB  - This is a retrospective study of 74 elderly patients (60 years of age or older)
      with idiopathic membranous nephropathy. They represented 23% of the total of 323
      cases of idiopathic membranous nephropathy who presented during the 19-year
      review period. The mean age of these patients was 67 years versus 41 in the
      younger-onset group. The median presenting serum creatinine in the elderly group
      was higher (1.3 mg/dL v 1.0 mg/dL, P < 0.001), and the median creatinine
      clearance calculated by Cockcroft-Gault to correct for age, gender, and weight
      was lower (55 mL/min v 95 mL/min, P < 0.0001). The incidence of chronic renal
      insufficiency, defined as a creatinine clearance of less than 50 mL/min, was
      significantly worse in the elderly after a mean observation period of 47 months
      (59% v 25%, P < 0.0001) although end-stage renal failure (ESRF) was not (18% v
      12%). The rate of change of renal function, however, as measured by the time to
      doubling of baseline creatinine, was similar in both groups, as was the complete
      remission rate. Forty-six percent of patients (33 of 74) in the elderly group
      received treatment: steroids alone (76%), immunosuppression drugs alone (9%), or
      a combination (15%). There was no benefit noted in terms of complete remission
      rate or incidence of chronic renal insufficiency. In summary, more elderly
      patients with membranous nephropathy develop chronic renal insufficiency, but
      this appears to be related to their age and decreased functional reserve, because
      the rate of decline in renal function after initiation of the disease is no
      different than in the younger age-group. The data also indicate that an accurate
      assessment of renal function in this older age-group requires an estimated or
      calculated creatinine clearance, given the inaccuracy when only serum creatinine
      is used. There was no evidence of improved outcome with prednisone therapy, and
      in view of the increased incidence of complications associated with this drug in
      the elderly as well as the decreased reserve at presentation, we suggest that
      routine steroid treatment of these patients should not be undertaken.

PMID- 9016891
TI  - Vasectomy is associated with an increased risk for urolithiasis.
AB  - We evaluated vasectomy as a potential risk factor for urolithiasis. Vasectomy is
      a common method of contraception among otherwise healthy men. This is also the
      population at highest risk for urolithiasis. We conducted a case-control study of
      patients in a large prepaid health maintenance organization. Cases were men
      experiencing initial episodes of urolithiasis, ascertained by reviewing radiology
      logs and medical records. The age-matched controls were men with no history of
      urolithiasis. In logistic regression models, the relative risk of urolithiasis
      for men with vasectomies compared with men without vasectomies was 1.9 for men
      younger than 46 years of age (95% confidence interval = 1.2 to 3.1, P = 0.005),
      and the relative risk was 0.9 (95% confidence interval = 0.5 to 1.5, P > 0.8) for
      men who were at least 46 years old. The relative risk of urinary calculi was 2.0
      (95% confidence interval 1.0 to 4.1, P < 0.05) for men with vasectomies 0 to 4
      years before evaluation compared with men without vasectomies, and the excess
      risk persisted as long as 14 years postvasectomy. Vasectomy was associated with a
      twofold increased risk for urolithiasis in men younger than 46 years of age. This
      increased risk may persist for up to 14 years postvasectomy. Given the large
      number of men who undergo vasectomy worldwide each year, the increased risk for
      urolithiasis among vasectomized men may result in substantial excess morbidity.

PMID- 9016892
TI  - Prediction of early death in end-stage renal disease patients starting dialysis.
AB  - Demand for dialysis for patients with end-stage renal disease is growing, as is
      the comorbidity of dialysis patients. Accurate prediction of those destined to
      die quickly despite dialysis could be useful to patients, providers, and society
      in making decisions about starting dialysis. To determine whether age and
      comorbidity accurately predict death within 6 months of first dialysis for end
      stage renal disease, a prospective cohort study of 822 patients starting dialysis
      at one of 11 Canadian centers was performed. Patient characteristics were
      recorded at first dialysis. Follow-up continued until death or study end (at
      least 6 months after enrollment). One hundred thirteen of 822 (13.7%) patients
      died within 6 months. Although an existing scoring system predicted prognosis,
      adverse scores greater than 9 were found in only 9.7% of those who died; only 52%
      of those who scored higher than 9 died within 6 months. No score cutoff point
      combined high true-positive and low false-positive rates for predicting early
      death. Age, severity of heart failure or peripheral vascular disease,
      arrhythmias, malnutrition, malignancy, or myeloma were independent prognostic
      factors identified in multivariate models. However, the best fit discriminant and
      logistic models were also unable to accurately predict death within 6 months.
      Clinicians were very accurate in assigning patients to prognostic groups up to a
      50% risk of death by 6 months, above which they tended to overestimate risk.
      However, clinicians were only marginally better than the predictive models in
      determining whether a given high-risk patient would die. The inability of a
      scoring system or clinical intuition to accurately predict death soon after
      starting dialysis for end-stage renal disease suggests that limiting access to
      dialysis on the basis of likely short survival may be inappropriate in Canada.

PMID- 9016893
TI  - The relationship of recirculation to access blood flow.
AB  - The relationship between vascular access recirculation and access blood flow has
      been obscured by measurement techniques that overestimate recirculation. We
      measured brachial artery blood flow (a surrogate for access blood flow) using
      Doppler ultrasound and access recirculation using a two-needle slow/stop flow
      method and the standard peripheral vein method in 77 chronic hemodialysis
      patients. These patients had 25 native arteriovenous fistulae and 52
      polytetrafluoroethylene grafts. Access recirculation by the slow/stop flow method
      was uniformly absent in these patients unless their access blood flow rate was
      less than the dialyzer blood flow rate. The peripheral vein method averaged 10.7%
      in these patients; many values were considerably higher. We conclude that access
      recirculation is a function of access blood flow and does not occur (in the
      absence of or reversed needle cannulation) unless access blood flow is markedly
      impaired.

PMID- 9016894
TI  - Pulse oxymetry evaluation of oxygen saturation in the upper extremity with an
      arteriovenous fistula before and during hemodialysis.
AB  - We noticed that some patients with arteriovenous (AV) fistula on chronic
      hemodialysis experience pain in the limb with the fistula a short time after
      being connected to the dialysis machine. We postulated that the pain is caused by
      relative ischemia and therefore performed this study to determine whether oxygen
      saturation (SaO2) of the extremities with AV fistula decreases during
      hemodialysis. Seventy-two patients with a side-to-side primary AV fistula were
      evaluated by pulse oxymetry. SaO2 was measured before hemodialysis and 20 minutes
      after initiation of dialysis. The contralateral arm served as a control. In 48
      patients, SaO2 difference between the arms of each patient before hemodialysis
      was less than 4%. SaO2 values of this group of patients did not change
      significantly 20 minutes after initiation of dialysis. In 24 patients, SaO2
      differences between the hands of each patient before hemodialysis were 4% or
      more. In this group of patients, SaO2 values of the hands with the AV fistula
      decreased significantly 20 minutes after hemodialysis from a mean of 90.85 +/-
      2.84% to 81.60 +/- 3.94 (P < 0.001). SaO2 remained unchanged in the contralateral
      arm. Nine patients in this group complained of pain and change in sensation in
      the arm with the fistula during hemodialysis. One patient complained of severe
      pain in the arm with the fistula before hemodialysis, and SaO2 was unmeasurable.
      We conclude that, in some patients, SaO2 of the arm with the AV fistula decreases
      only during hemodialysis. This phenomenon may be symptomatic. A predialysis SaO2
      difference of 4% or more between the arms predicts decreased SaO2 of the arm with
      the AV fistula during hemodialysis.

PMID- 9016895
TI  - A longitudinal study on the effect of nifedipine therapy and its discontinuation
      on [Ca2+]i and proliferation of B lymphocytes of dialysis patients.
AB  - The abnormalities in cytosolic calcium ([Ca2+]i) and proliferation of B cells in
      uremic patients are significantly improved by treatment with nifedipine. The
      rapidity with which this agent induces its beneficial effect and whether these
      derangements reemerge after cessation of therapy are not known. We studied six
      hemodialysis patients before, during, and after treatment with nifedipine. Before
      treatment, [Ca2+]i of B cells was markedly elevated (125 +/- 4.3 nmol/L) and
      their proliferation markedly reduced (5.2 +/- 0.36 x 10(3) cpm). After 1 month of
      therapy, [Ca2+]i fell significantly (P < 0.01) to 95 +/- 1.7 nmol/L and to a
      normal value of 84 +/- 1.6 after 2 months. The levels of [Ca2+]i rose
      significantly (P < 0.01) to 95 +/- 2.3 nmol/L after 1 month of cessation of
      therapy and were 115 +/- 2.8 nmol/L by 2 months. Proliferation of B cells
      improved significantly (P < 0.01) after 1 month of therapy (9.4 +/- 1.1 x 10(3)
      cpm) with further improvement during the subsequent month, reaching a normal
      value (12.2 +/- 1.1 x 10(3) cpm) by the end of the 2 months. Proliferation of B
      cells decreased after cessation of therapy and was 5.2 +/- 0.17 x 10(3) cpm after
      2 months, a value similar to the pretreatment level. The blunted inhibitory
      effect of PTH-(1-84) on B cell proliferation was reversed by nifedipine treatment
      and reappeared after discontinuation of therapy. Also, serum globulin levels
      increased after administration of nifedipine and decreased again after cessation
      of treatment. The results show that nifedipine rapidly reversed the elevation in
      [Ca2+]i of B cells, the impairment in their proliferation, and the blunted
      inhibitory effect of PTH on B cell proliferation, and was associated with
      increased serum globulin levels. These derangements reemerged after cessation of
      therapy. These data indicate that nifedipine therapy is effective in the
      management of the abnormalities in B cell metabolism and function in hemodialysis
      patients. The treatment with this drug must be maintained to sustain its
      beneficial effects. Other calcium channel blockers may also be effective, but
      their effects were not examined in the current study.

PMID- 9016896
TI  - Prospective analysis of the factors influencing the antibody response to
      hepatitis B vaccine in hemodialysis patients.
AB  - Hepatitis B vaccine is effective in producing protection against hepatitis B
      virus (HBV) infection in hemodialysis (HD) patients, but the antibody response is
      variable. To identify those factors implicated in the vaccine response, in a
      prospective study over a 24-month period, we vaccinated 80 seronegative patients
      on HD (group A) and monitored clinical, biochemical, and immunologic parameters.
      The protective immunity acquired by vaccination was compared with that developed
      through HBV infection in 22 age-matched HD patients (group B). The anti-HBs
      antibody-seronegative patients followed a four-dose vaccination schedule (0, 1,
      2, and 6 months) with 40 microg DNA-recombinant hepatitis B vaccine. One month
      after vaccination, 77.5% of the patients had seroconverted, and 72.5% achieved
      high antibody response, whereas 22.5% were nonresponders. Patients aged younger
      than 40 years seroconverted 100%; those aged 40 to 60 years, 75% (P < 0.01); and
      patients older than 60 years, 74% (P < 0.001). No differences between responders
      and nonresponders concerning sex, time on HD, HD dose, nutritional status,
      hemoglobin level, HD membrane, iPTH level, calcitriol treatment, or number of
      transfusions during vaccination were found. The presence of other factors, such
      as recombinant human erythropoietin (rHuEPO) therapy or hepatitis C virus (HCV)
      infection, did not significantly influence antibody responses to hepatitis B
      immunization. A greater frequency of DR3 (53.8% v 25.7%, P < 0.05), DR7 (53.8% v
      18.6%, P < 0.01), and DQ2 (76.9% v 44.1%, P < 0.05), and a lesser frequency of A2
      (7.7% v 37.2%, P < 0.05) were found in nonresponders compared with responders.
      Eighteen months after vaccination, the analysis showed similar antibody titers
      but lower seroconversion rates in group A as compared with group B. In
      conclusion, unresponsiveness to hepatitis B vaccine in HD patients was related to
      factors such as older age, the presence of DR3, DR7, and DQ2, and the absence of
      A2 alleles. Although the seroprotection produced by the vaccine was less than
      that achieved through natural HBV infection, our protocol of vaccination was
      sufficiently immunogenic and provided lasting protection.

PMID- 9016897
TI  - In vitro effects of glucose polymer-containing peritoneal dialysis fluids on
      phagocytic activity.
AB  - Commercially available peritoneal dialysis fluids (PDFs) are known to impair
      peritoneal cellular defense mechanisms. We have investigated the influence of
      glucose polymer-containing PDFs on phagocytic function in vitro.
      Polymorphonuclear neutrophils (PMNLs) and monocytes (MNs) from 10 continuous
      ambulatory peritoneal dialysis patients and 10 healthy donors were incubated in
      PDFs containing either 7.5% icodextrin (glucose polymer) or 1.5% glucose at
      original pH and pH 7.4. Chemiluminescence response and H202 production were
      measured following stimulation with preopsonized Staphylococcus epidermidis or
      phorbol myristate acetate. Phagocytosis of radiolabeled bacteria and killing
      capacity of the cells were determined. A comparison of the impact of glucose
      polymer versus glucose-containing solutions at their original pH on the oxidative
      metabolism of the cells showed a highly significant difference (P < 0.0001) in
      favor of glucose polymers for H202 production of PMNLs (7.78 +/- 4.5 nmol
      cytochrome C reduction/10(6) cells/min v 1.11 +/- 0.67 nmol cytochrome C
      reduction/10(6) cells/min) and MNs (7.66 +/- 3.6 nmol cytochrome C
      reduction/10(6) cells/min v 1.29 +/- 0.86 nmol cytochrome C
      reduction/10(6)cells/min). Correspondingly, PMNLs and MNs incubated in glucose
      polymers showed a significantly higher chemiluminescence response irrespective of
      the stimulant used (P < 0.0001). Applying the killing assay on PMNLs also
      revealed a significantly higher percentage of inactivated bacteria (45.5% +/-
      11.0% v 29.2% +/- 15.5%; P < 0.05). After adjustment of pH to 7.4, a significant
      difference could only be found for H202 production of PMNLs in favor of glucose
      polymers (16.73 +/- 6.98 nmol cytochrome C reduction/10(6) cells/min v 11.65 +/-
      5.37 nmol cytochrome C reduction/10(6) cells/min; P < 0.05). In addition, we
      compared the glucose-polymer solution to an otherwise equally composed
      equiosmolar solution that contained 0.274% glucose instead of glucose polymers.
      No significant differences were detected with any of the tests applied. Our data
      suggest that glucose polymer solutions are comparatively less suppressive to
      phagocytic function than currently used glucose-containing PDFs. This effect may
      be attributed to the low osmolarity of these solutions.

PMID- 9016898
TI  - The renoprotective properties of angiotensin-converting enzyme inhibitors in a
      chronic model of membranous nephropathy are solely due to the inhibition of
      angiotensin II: evidence based on comparative studies with a receptor antagonist.
AB  - In several models of renal disease progression, angiotensin-converting enzyme
      (ACE) inhibitors reduced proteinuria and limited glomerulosclerosis, which
      suggested that reduction of renal angiotensin II (Ang II) activity is crucial for
      the preservation of glomerular structure and function. However, it cannot be
      ruled out that other hormonal systems, including inhibition of the bradykinin
      breakdown, also play a role. We compared the effects of chronic treatment with
      the ACE inhibitor lisinopril with those of a specific Ang II receptor antagonist,
      L-158,809, on proteinuria and renal injury in passive Heymann nephritis (PHN), a
      model of immune renal disease that closely resembles human membranous
      nephropathy, with long-lasting proteinuria followed by tubulointerstitial damage
      and glomerulosclerosis. Passive Heymann nephritis was induced with 0.5 mL/100 g
      of rabbit anti-Fx1A antibody in 24 male Sprague-Dawley rats. The animals were
      divided into three groups of eight rats each, and were given the following in the
      drinking water on a daily basis: lisinopril (40 mg/L), L-158,809 (50 mg/L), or no
      therapy. Treatment started at day 7 (proteinuria was already present) and lasted
      12 months. Eight normal rats were used as controls. Untreated PHN rats developed
      hypertension, while rats with PHN given lisinopril or L-158,809 all had systolic
      blood pressure values even lower than those of normal rats. Urinary protein
      excretion progressively increased with time in untreated PHN rats, who developed
      tubulointerstitial damage and glomerulosclerosis. Both lisinopril and L-158,809
      exhibited a potent antiproteinuric effect and preserved glomerular and tubular
      structural integrity at a similar extent. Renal gene expression of transforming
      growth factor-beta and extracellular matrix proteins was also effectively reduced
      by the two treatments. These results indicate that ACE inhibitors and Ang II
      receptor antagonists are equally effective in preventing renal injury in PHN and
      suggest that the renoprotective effects of ACE inhibitors in this model are
      solely due to inhibition of Ang II.

PMID- 9016899
TI  - Gender and the effect of gonadal hormones on the progression of inherited
      polycystic kidney disease in rats.
AB  - Human autosomal dominant polycystic kidney disease (ADPKD) is a common inherited
      disease and displays a gender dimorphism in renal disease progression. Han:SPRD
      Cy rats manifest a form of ADPKD that is similar in many respects to that seen in
      humans. In Han:SPRD rats, male Cy/+ rats have more prominent renal changes and
      develop renal failure at an early age, whereas female Cy/+ rats exhibit less
      severe renal cystic change and have normal renal function until advanced age. To
      determine whether the male gonadal hormone, testosterone, contributes to this
      gender dimorphism, males were sham operated or castrated; some castrated rats
      were repleted with 5alpha-dihydrotestosterone. Female rats were sham operated or
      ovariectomized before sham operation or testosterone treatment. All treatments
      started at 4 weeks of age and ended at 10 weeks of age. Renal enlargement, cystic
      change, and renal function were assessed. In the males, castration reduced renal
      enlargement and cystic change; testosterone treatment abrogated these effects.
      Neither of these manipulations affected azotemia in male Cy/+ rats. In the
      females, testosterone was renotropic for both normal and cystic kidneys. In the
      Cy/+ females, testosterone treatment caused azotemia and an increase in the
      severity of the PKD. Ovariectomy blunted the effect of testosterone on cystic
      kidney enlargement. Testosterone treatment did not completely erase the gender
      associated differences in azotemia in the Cy/+ rat. These data confirm the
      renotropic effects of testosterone and indicate that testosterone influences the
      progression of renal cystic change in male and female rats with ADPKD.

PMID- 9016900
TI  - Acute renal failure due to postinfectious glomerulonephritis during pregnancy.
AB  - Acute renal failure is a rare but potentially devastating complication of
      pregnancy. Among its many potential causes is acute postinfectious
      glomerulonephritis. We describe a case of acute renal failure during pregnancy,
      provide the histologic features of the renal biopsy, and discuss the differential
      diagnosis. Postinfectious glomerulonephritis can present rapidly after clinical
      infection and cause acute renal failure in pregnancy.

PMID- 9016901
TI  - Systemic lupus erythematosus with membranous glomerulonephritis and uterine
      vasculitis.
AB  - We report a case of lupus vasculitis with uterine localization and concurrent
      membranous nephropathy. Immunofluorescence study suggested the occurrence of an
      immune complex nephropathy and a pauci-immune pathogenesis of vasculitis. Our
      case points out the event of tissue damage in two organs mediated by different
      pathogenetic mechanisms. In addition, uterine vasculitis without pregnancy may be
      observed in patients with systemic lupus erythematosus nephritis.

PMID- 9016902
TI  - Endotheliopathy: a continuum of hemolytic uremic syndrome due to mitomycin
      therapy.
AB  - Hemolytic uremic syndrome (HUS) is a rare, often fatal complication of mitomycin
      C therapy. It is generally accepted that HUS is, in part, caused by endothelial
      cell dysfunction. Endothelial cells modulate blood flow, blood pressure, and
      myointimal proliferation. Endothelial cells synthesize and release products that
      modulate vascular tone and regulate vascular smooth muscle cell growth. We
      describe a patient who developed HUS secondary to mitomycin C, resulting in end
      stage renal disease and necessitating chronic hemodialysis. Over several months,
      the patient subsequently developed multisystem organ failure involving the heart,
      liver, and intestine that was associated with angiographically documented small,
      distal vessel occlusive disease and ultrasonographically identified coronary
      artery intimal hyperplasia. We propose that a diffuse ongoing endothelial cell
      dysfunction (ie, endotheliopathy) is the putative mechanism for this patient's
      clinical course. To our knowledge, this continuum of HUS presenting as a
      multisystem, progressive disorder has not been previously reported.

PMID- 9016903
TI  - Henoch-Schonlein purpura with immunoglobulin A nephropathy and abnormalities of
      immunoglobulin A in a Wiskott-Aldrich syndrome carrier.
AB  - Abnormalities of immunoglobulin A1 (IgA1) glycosylation have been described in
      patients with IgA nephropathy (IgAN), whether primitive or secondary to Henoch
      Schonlein purpura. The Wiskott-Aldrich syndrome, an X-linked recessive disorder,
      is associated with abnormalities of IgA. Renal involvement with mesangial IgA
      deposition identical to that found in IgAN has been reported during this
      affection. We report the case of a female carrier of the Wiskott-Aldrich syndrome
      presenting with Henoch-Schonlein purpura and abnormalities of IgA glycosylation,
      as previously reported in patients with IgAN. The galactosylation abnormalities
      of IgA could be linked to the patient's status as carrier of the Wiskott-Aldrich
      syndrome and could contribute to the pathogenesis of IgAN.

PMID- 9016904
TI  - Correction of hypercalcemia and hypophosphatemia by hemodialysis using a
      conventional, calcium-containing dialysis solution enriched with phosphorus.
AB  - We report a woman with hypercalcemia and hypophosphatemia due to primary
      hyperparathyroidism. Hemodialysis using a phosphorus-enriched, conventional,
      calcium-containing dialysis solution resulted in the simultaneous correction of
      hypercalcemia and hypophosphatemia, resulting in a marked improvement of the
      patient's impaired mental status.

PMID- 9016905
TI  - The clinical spectrum of chronic metabolic acidosis: homeostatic mechanisms
      produce significant morbidity.
AB  - Chronic metabolic acidosis is a process whereby an excess nonvolatile acid load
      is chronically placed on the body due to excess acid generation or diminished
      acid removal by normal homeostatic mechanisms. Two common, often-overlooked
      clinical conditions associated with chronic metabolic acidosis are aging and
      excessive meat ingestion. Because the body's homeostatic response to these
      pathologic processes is very efficient, the serum HCO3- and blood pH are
      frequently maintained within the "normal" range. Nevertheless, these homeostatic
      responses engender pathologic consequences, such as nephrolithiasis, bone
      demineralization, muscle protein breakdown, and renal growth. Based on this, the
      concept of eubicarbonatemic metabolic acidosis is introduced. Even in patients
      with a normal serum HCO3- and blood pH, it is important to treat the acid load
      and prevent pathologic homeostatic responses. These homeostatic responses, as
      well as the mechanisms responsible for their initiation, are reviewed.

PMID- 9016906
TI  - An update on new immunosuppressive drugs undergoing preclinical and clinical
      trials: potential applications in organ transplantation.
AB  - Recent advances in immunobiology and immunopharmacology have led to a better
      understanding of the actions of immunosuppressive drugs. Over the past 2 years, a
      number of new agents have been approved for use in solid organ transplant
      recipients. In addition, new immunosuppressive agents are being tested in
      preclinical and clinical trials, leading to the promise of an exciting future in
      organ transplantation. This report reviews the mechanisms of action and the
      potential future role of these agents in clinical transplantation.

PMID- 9016907
TI  - In vivo functional interaction between phencyclidine binding sites and sigma
      receptors to produce head-weaving behavior in rats.
AB  - To investigate the in vivo functional interaction between phencyclidine (1-(1
      phenylcyclohexyl)piperidine; PCP) binding sites and sigma receptors, we examined
      the effects of sigma receptor ligands on stereotyped head-weaving behavior
      induced by PCP, a putative PCP/sigma receptor ligand, and (+)-5-methyl-10,11
      dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imin e ((+)-MK-801; dizocilpine), a
      selective PCP binding site ligand, in rats. PCP (7.5 mg/kg, i.p.)-induced head
      weaving behavior was inhibited by both N,N-dipropyl-2-[4-methoxy-3-(2
      phenylethoxy)-phenyl]-ethylamine (NE-100; 0.03-1.0 mg/kg, p.o.), a selective
      sigma1 receptor ligand, and alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1
      piperidine butanol (BMY-14802; 3 and 10 mg/kg, p.o.), a prototype sigma receptor
      ligand, in a dose-dependent manner, whereas NE-100 (0.1-1.0 mg/kg, p.o.) and BMY
      14802 (3 and 10 mg/kg, p.o.) did not inhibit dizocilpine (0.25 mg/kg, s.c.)
      induced head-weaving behavior. These results suggest that NE-100 and BMY-14802
      act via sigma receptors. Dizocilpine-induced head-weaving behavior was
      potentiated by 1,3-di-o-tolyl-guanidine (DTG; 0.03-0.3 microg/kg, i.v.) and (+)-3
      (3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP; 3 and 6 mg/kg, i.p.),
      sigma1/sigma2 receptor ligands, as well as by (+)-N-allyl-normetazocine ((+)-SKF
      10,047: 8 mg/kg, i.p.), a sigma1 receptor ligand, while DTG (0.3 microg/kg,
      i.v.), (+)-3-PPP (6 mg/kg, i.p.) and (+)-SKF-10,047 (8 mg/kg, i.p.) did not
      induce this behavior. Potentiation of dizocilpine-induced head-weaving behavior
      by DTG (0.3 microg/kg, i.v.), (+)-3-PPP (6 mg/kg, i.p.) and (+)-SKF-10,047 (8
      mg/kg, i.p.) was completely blocked by NE-100 (0.1 mg/kg, p.o.) and BMY-14802 (10
      mg/kg, p.o.). These results suggest that PCP binding sites and sigma receptors
      are involved in PCP-induced head weaving behavior, and that sigma1 receptors play
      an important role in modulation of the head-weaving behavior.

PMID- 9016908
TI  - The role of 5-HT1A and 5-HT1B receptors in antidepressant drug actions in the
      mouse forced swimming test.
AB  - The forced swimming test is a behavioural model developed to predict the efficacy
      of antidepressant drugs. Few studies have been aimed at evaluating the mechanism
      of action of antidepressants in the forced swimming test. The present study was
      designed in order to further evaluate the mode of action of antidepressants in
      the forced swimming test, by using selective agonists and antagonists at 5-HT1A
      and 5-HT1B receptor sites. Agonists/antagonists and antidepressants were
      administered 45 min and 30 min, respectively, prior to testing. Prior
      administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg,
      i.p.) induced anti-immobility effects with the tricyclic antidepressant
      imipramine (8 mg/kg, i.p.) and noradrenaline uptake inhibitors maprotiline (8
      mg/kg, i.p.) and desipramine (16 mg/kg, i.p.), but not with fluoxetine (16 mg/kg,
      i.p.), citalopram (16 mg/kg, i.p.) or fluvoxamine (8 mg/kg, i.p.). These effects
      were antagonised by prior administration of 1-(2-methoxyphenyl)-4-[-(2
      phthalimido)butyl]piperazine) (NAN 190) (0.5 mg/kg, i.p.). On the other hand,
      pretreatment with (+/-)-pindolol (32 mg/kg, i.p.) potentiated the effects of the
      selective serotonin reuptake inhibitors and was devoid of any activity with
      imipramine (8 mg/kg, i.p.), maprotiline (8 mg/kg, i.p.) or desipramine (16 mg/kg,
      i.p.). Prior administration of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H
      indole (RU 24969) enhanced the antidepressant-like effects of the selective
      serotonin reuptake inhibitors and imipramine (8 mg/kg, i.p.) in the forced
      swimming test. The anti-immobility effects of the selective serotonin reuptake
      inhibitors in the forced swimming test seem to be mediated by presynaptic 5-HT1A
      receptors as well as postsynaptic 5-HT1B receptors. Antidepressant-like effects
      of the noradrenaline uptake inhibitors seem, on the other hand, to be mediated by
      postsynaptic 5-HT1A receptors. Considering the variety of 5-HT receptors, it is
      possible that other subtypes may participate in the anti-immobility effects of
      antidepressants in the forced swimming test.

PMID- 9016909
TI  - Antidepressant-like effects of CCK(B) receptor antagonists: involvement of the
      opioid system.
AB  - RB 101 (N-[(R,S)-2-benzyl-3-[(S)-2-amino-4-methylthiobutyldithio]-1-oxopr opyl]-L
      -phenylalaninebenzyl ester), a systemically active inhibitor of enkep halin
      catabolism, has been shown to elicit antidepressant-like effects in mice, both in
      the forced-swimming and in the conditioned suppression of the mobility tests. The
      same type of response has been also observed following administration of the
      cholecystokinin CCK(B) receptor antagonist L-365,260 ((3R)-(+)-N-(2,3-dihydro-1
      methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)-3 -methylphenylurea). In
      terestingly, the delta-opioid receptor antagonist naltrindole (17
      cyclopropylmethyl-6,7-dehydro-4,5alpha-epoxy-3,14-dihydroxy-6, 7,2'-3'
      indolomorphinan) blocks the effect of both RB 101 and L-365,260 in the
      conditioned suppression of the motility test. In this work we have investigated
      the involvement of the opioid system in the antidepressant response to the CCK(B)
      receptor antagonist L-365,260 in the forced-swimming test in mice. The effect of
      L-365,260 was decreased by the delta-opioid receptor antagonist naltrindole.
      Furthermore, the CCK(B) receptor agonist, BC 264 (Boc-Tyr(OSO3H)-gNle-mGly-Trp
      (NMe)Nle-Asp-Phe-NH2), blocked the antidepressant-like effect of RB 101 while CCK
      8 (H-Asp-Tyr(OSO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) enhanced the effect of this
      drug, probably through stimulation of central CCK(A) receptors, since the CCK(A)
      receptor antagonist devazepide ((3S)-(-)-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H
      1,4-benzodiazepin++ +-3-yl)-1H-indole-2 -carboxamide) abolished the CCK-8-induced
      potentiation of the RB 101 effect. In addition, RB 101 enhanced the effect of L
      365,260. Such an effect was blocked by the delta-opioid receptor antagonist
      naltrindole. These data further support the involvement of opioid receptors in
      the antidepressant-type effect induced by CCK(B) receptor blockers and support
      the hypothesis of a regulatory role of CCK in the activity of the endogenous
      opioid system. As in other experimental paradigms, CCK(A) and CCK(B) receptor
      stimulation appears to have opposite effects in modulating opioidergic activity.

PMID- 9016910
TI  - Motor depressant effects of systemically administered polyamines in mice:
      involvement of central NMDA receptors.
AB  - The systemic administration of polyamines (s.c.) produced a dose-dependent motor
      depression. With high doses the depressant effect was long-lasting and the
      animals showed signs of toxicity. ED50 values for spermine, spermidine and
      putrescine were 38, 90 and 251 mg/kg respectively. The motor depression induced
      by the systemic administration of N-methyl-D-aspartate (NMDA; 25 mg/kg i.p.) was
      used as a model for studying the interactions between polyamines and the NMDA
      receptor. Results indicate that (1) the motor effects elicited by NMDA are very
      similar to those induced by polyamines at ED50 doses; (2) polyamines, even at non
      active doses, potentiate the motor depressant effect induced by NMDA; (3) the
      NMDA receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,1 0-imine (MK-801; 0.5 mg/kg i.p.), abolishes the
      depressant effect elicited by NMDA and by polyamines, even at toxic doses; (4)
      amphetamine (1.5 mg/kg i.p.) does not counteract the motor depressant effects of
      NMDA or polyamines. On the other hand, the adenosine receptor antagonist,
      theophylline (30 mg/kg i.p.), counteracts NMDA- but not polyamine-induced motor
      depression. The concentration of polyamines in the brain is modified after their
      systemic administration at high doses and at the ED50 dose of putrescine. In
      conclusion, the data suggest that the NMDA receptor could be a target mediating
      the motor effect elicited by polyamines. They also show that the quantitative
      analysis of the motor effects elicited by non-convulsant doses of NMDA might be a
      powerful tool for studying in vivo the interaction between neurotransmission
      systems involved in the regulation of motor activity.

PMID- 9016911
TI  - Effects of combined nimodipine and metrifonate on rat cognition and cortical EEG.
AB  - The present study investigated if short-term treatment with an L-type Ca2+
      channel inhibitor, nimodipine, can stimulate cognitive functioning and cortical
      electroencephalograph (EEG) arousal, and potentiate the effect of a
      cholinesterase inhibitor, metrifonate. Pretraining administration of nimodipine
      (3, 10 and 30 mg/kg, p.o.) had no effect on water maze and passive avoidance
      behavior of young neurologically intact controls, or water maze and passive
      avoidance performance failure induced by scopolamine pretreatment (i.p.; 0.4
      mg/kg during the water maze and 2.0 mg/kg during the passive avoidance study),
      medial septal lesioning, or aging. Furthermore, nimodipine (3, 10 and 30 mg/kg,
      p.o.) had no effect on the improvement by metrifonate (10 mg/kg, p.o.) of the
      water maze and passive avoidance failure induced by scopolamine pretreatment or
      medial septal lesioning, nor did it affect the potential of metrifonate (30
      mg/kg. p.o.) to improve the water maze or passive avoidance behavior of aged
      rats. Finally, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on
      spontaneously occurring thalamically generated neocortical high-voltage spindles
      or spectral EEG activity of young controls, nor did it alleviate the spectral EEG
      abnormality induced by scopolamine (0.2 mg/kg, i.p.) administration. Also, the
      combination of nimodipine 3 or 10 mg/kg and a subthreshold dose of metrifonate 10
      mg/kg could not suppress high-voltage spindles or scopolamine treatment-induced
      spectral EEG activity abnormalities. According to the present results, short-term
      treatment with nimodipine does not stimulate cognitive functions or increase
      cortical EEG arousal, and does not block or potentiate the propensity of
      metrifonate to improve cognitive performance of rats.

PMID- 9016912
TI  - Effects of diabetes on methamphetamine-induced place preference in mice.
AB  - The effects of diabetes on methamphetamine-induced place preference in mice were
      examined. Methamphetamine caused a dose-dependent place preference in both
      diabetic and non-diabetic mice. Methamphetamine preferentially induced place
      preference in diabetic mice as compared to those in non-diabetic mice. Indeed,
      methamphetamine-induced place preference at a dose of 0.3 mg/kg in diabetic mice
      was similar to that at 3 mg/kg in non-diabetic mice. Furthermore, methamphetamine
      induced place preference in both diabetic and non-diabetic mice was significantly
      antagonized by pretreatment with quinpirole, a dopamine D2/D3 receptor agonist.
      Methamphetamine-induced place preference was also antagonized by pretreatment
      with 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), a selective dopamine
      D3 receptor agonist. On the other hand, 7-OH-DPAT produced significant place
      aversion in non-diabetic mice. 7-OH-DPAT produced neither place preference nor
      place aversion in diabetic mice. These results suggest that methamphetamine
      induced place preference may be modulated by dopamine D3 receptors. Furthermore,
      increased dopamine neurotransmission associated with the down-regulation of
      presynaptic dopamine D3 receptor-mediated functions may account for the
      enhancement of methamphetamine's reinforcing effect in diabetic mice.

PMID- 9016913
TI  - Effects of a range of dopamine receptor agonists and antagonists on ethanol
      intake in the rat.
AB  - The aim of this study was to assess the effects of a range of dopaminergic agents
      on consumption of an ethanol solution (10% ethanol, 3% glucose) in rats. A two
      bottle, free-choice paradigm was used following induction of ethanol consumption
      and preference in standard laboratory rats. The model used provides a robust and
      reliable level of ethanol oral administration in normal laboratory rats. Both
      ethanol intake and preference were reduced by a dopamine D1 receptor partial
      agonist, SFK 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol
      hydrochloride), in a dose-dependent manner. The dopamine D2/D3 receptor agonist 7
      OH-DPAT ((+/-)-7-hydroxy-N,N-(di-n-propyl-2-aminotetralin)) at the lowest dose of
      0.01 mg/kg increased both ethanol intake and preference. At higher doses (0.03
      0.1 mg/kg) no significant effects were found. The dopamine D1 receptor antagonist
      SCH 23390 (R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8
      ol), dopamine D2/D3 receptor antagonist raclopride and 5-HT2/D2 receptor
      antagonist risperidone did not affect ethanol consumption, although all at high
      doses induced a significant decrease in water intake, indicating a non-specific
      decrease in consummatory behavior with these compounds. These results suggest the
      involvement of the dopaminergic system in ethanol intake and ethanol
      reinforcement with dopamine D1 and D2/D3 receptors playing opposing roles.
      Blockade of dopamine D2 receptors had no selective effect on ethanol consumption
      and ethanol preference.

PMID- 9016914
TI  - D-cycloserine, a glycine site agonist, reverses working memory failure by
      hippocampal muscarinic receptor blockade in rats.
AB  - D-Cycloserine, a partial agonist at the glycine binding site on the NMDA
      receptor/channel complex, did not affect the number of errors (attempts to pass
      through two incorrect panels of the three-panel gates at four choice points) in
      the working memory task with a three-panel runway setup, when injected
      bilaterally at 1 or 10 microg/side into the dorsal hippocampus. Intrahippocampal
      administration of the muscarinic receptor antagonist scopolamine (3.2
      microg/side) significantly increased the number of working memory errors. The
      increase in working memory errors induced by intrahippocampal 3.2 microg/side
      scopolamine was significantly reduced by concurrent infusion of 1 and 10
      microg/side D-cycloserine. These results suggest that positive modulation of the
      NMDA receptor/channel through activation of the glycine site can compensate
      dysfunction of hippocampal cholinergic neurotransmission involved in working
      memory function.

PMID- 9016915
TI  - The antinociceptive activity of kappa- but not delta-opioid receptor agonists is
      maintained in morphine-tolerant neuropathic rats.
AB  - The antinociceptive effect of the preferential mu-opioid receptor agonist
      morphine (1 mg/kg i.v.), the delta-opioid receptor agonists, DTLET ([D
      Thr2,Leu5]enkephalin-Thr) (3 and 6 mg/kg i.v.) and BUBUC ([D
      Cys(StBu)2,Leu5]enkephalin-Thr(OtBu) (3 mg/kg i.v.), and the kappa-opioid
      receptor agonist U-69,593 (trans-3,4-dichloro-N-methyl-N-[7-(1
      pyrrolidinyl)cyclohexil]benze neacetamide methanesulfonate) (0.25, 0.5 and 0.75
      mg/kg i.v.) was evaluated in mononeuropathic (chronic constriction of the common
      sciatic nerve) rats. The rats were pretreated s.c. with 10 mg/kg of morphine, or
      saline, twice daily from day 12 to day 16 after the surgery. In morphine
      pretreated rats, the antinociceptive effect of morphine on the vocalization
      threshold to paw pressure was greatly reduced, as compared to the saline
      pretreated group. The antinociceptive effect of DTLET and BUBUC had also
      disappeared in the morphine-pretreated rats. By contrast, the potent
      antinociceptive effect of U-69,593 was not affected by the morphine pretreatment.
      Furthermore, the effect of U-69,593 was reversed by the specific kappa-opioid
      receptor antagonist nor-binaltorphimine (1 and 2 mg/kg i.v.). These results
      suggest that in mononeuropathic rats, morphine pretreatment results in cross
      tolerance to delta- but not to kappa-opioid receptor agonists.

PMID- 9016916
TI  - Dopamine D3 receptors are not involved in the induction of c-fos mRNA by
      neuroleptic drugs: comparison of the dopamine D3 receptor antagonist GR103691
      with typical and atypical neuroleptics.
AB  - The effect of acute and chronic administration of dopamine receptor antagonists
      on the expression of mRNA encoding the cellular immediate-early gene c-fos was
      investigated in rat brain by in situ hybridization using 35S-labelled
      oligonucleotide probes. The selective dopamine D3 receptor antagonist GR103691
      had no effect on the level of c-fos mRNA after acute or chronic treatment. Acute
      treatment with haloperidol increased the level of c-fos mRNA in the caudate
      putamen, nucleus accumbens shell and core, olfactory tubercle and parietal
      cortex. After chronic treatment with haloperidol increases in the level of c-fos
      mRNA in the caudate-putamen and nucleus accumbens core were no longer observed.
      The increase in the level of c-fos mRNA in the nucleus accumbens shell was
      attenuated but still significantly elevated above the level measured in vehicle
      treated animals. In the olfactory tubercle, parietal cortex, frontal cortex and
      cingulate cortex the level of c-fos mRNA was decreased after chronic haloperidol
      treatment. Acute sulpiride treatment reduced the level of c-fos mRNA in the
      olfactory tubercle, parietal cortex and cingulate cortex. After chronic treatment
      with sulpiride the level of c-fos mRNA was reduced in the dorsal caudate-putamen
      only. Acute clozapine treatment increased the level of c-fos mRNA in the nucleus
      accumbens shell and islands of Calleja. After chronic treatment with clozapine
      the level of c-fos mRNA remained elevated in the islands of Calleja but not in
      the nucleus accumbens shell. These results indicate that acute and chronic
      blockade of dopamine D3 receptors does not cause induction of c-fos transcription
      in limbic, striatal or cortical regions of rat brain. This study also
      demonstrated that acute blockade of dopamine receptors with haloperidol,
      sulpiride and clozapine induced different regionally specific patterns of c-fos
      expression which were altered after chronic blockade.

PMID- 9016918
TI  - Fragments of galanin message-associated peptide (GMAP) modulate the spinal flexor
      reflex in rat.
AB  - We have previously reported that galanin message-associated peptide (GMAP), a
      fragment of galanin precursor protein, is present in dorsal root ganglion cells
      and upon intrathecal (i.t.) administration influences the spinal nociceptive
      flexor reflex in a complex manner in the rat. GMAP elicited a moderate
      facilitation of the flexor reflex, but when administered prior to conditioning
      stimulation of C-afferents, it dose dependently blocked spinal cord
      hyperexcitability. The present study examined the effects of four fragments of
      GMAP-(1-60), GMAP-(1-12), GMAP-(10-24), GMAP-(25-44) and GMAP-(37-60), on the
      flexor reflex and compared them with the effects of the complete peptide
      sequence. All four GMAP fragments facilitated the flexor reflex. However, this
      effect was dose-dependent only for GMAP-(1-12) and the effect of GMAP-(1-12) was
      stronger than GMAP-(1-60). In contrast, only GMAP-(25-44) dose dependently
      blocked the facilitation of the flexor reflex induced by the C-fiber conditioning
      stimulation. The potency of the blocking effect of GMAP-(25-44) was one order of
      magnitude lower than that of GMAP-(1-60). The results indicated that two
      fragments of GMAP are pharmacologically active and produce effects which are
      similar to the full sequence. It is possible that the complex effect of GMAP may
      be mediated by different subtypes of GMAP receptors which recognize different
      portions of the GMAP sequence.

PMID- 9016917
TI  - In vivo blockade of thalamic GABA(B) receptors increases excitatory amino-acid
      levels.
AB  - The effect of intrathalamic application of GABA(B) receptor antagonists on the
      basal excitatory amino-acid levels was studied using microdialysis probes
      implanted in the dorsal lateral geniculate nucleus and in the ventrobasal
      complex. In both nuclei, continuous perfusion of the GABA(B) receptor antagonist
      3-aminopropyl-(diethoxymethyl)-phosphinic acid (CGP 35348) produced an increase
      in the extracellular concentration of aspartate and (to a lesser extent)
      glutamate, but no change was observed in the level of taurine, the main amino
      acid involved in the regulation of brain osmolarity processes. In contrast, 3
      amino-2-hydroxy-2-(4-chlorophenyl)-propanesulphonic acid (2-hydroxy-saclofen),
      another GABA(B) receptor antagonist, failed to affect the extracellular
      concentration of aspartate, glutamate and taurine. Thus, the basal level of
      excitatory amino acids in the thalamus in vivo is under the control of CGP 35348
      sensitive GABA(B) receptors.

PMID- 9016919
TI  - Pharmacological characterization of neuropeptide Y-(2-36) binding to neuropeptide
      Y Y1 and Y2 receptors.
AB  - Neuropeptide Y-(2-36) has been reported by several research groups to be a more
      potent orexigenic agent than intact neuropeptide Y. Therefore, it has been
      proposed that a novel 'Y1 variant' may modulate ingestive behavior. To define the
      receptor subtype involved in neuropeptide Y-stimulated feeding behavior, we
      evaluated the binding properties of neuropeptide Y-(2-36) and [125I]neuropeptide
      Y-(2-36) in established neuropeptide Y1 and Y2 containing cell lines and tissues.
      Neuropeptide Y-(2-36) displaced [125I]peptide YY binding to SK-N-MC cells
      (neuropeptide Y Y1 receptors) with a Ki of 3.69 nmol and SK-N-BE(2) cells
      (neuropeptide Y Y2 receptors) with a Ki of 3.08 nmol. Neuropeptide Y-(2-36) also
      displaced [125I]peptide YY binding to rat cerebral cortex, hippocampus and
      olfactory bulb with similar affinities. To examine the brain distribution of
      [125I]peptide YY, [125I]neuropeptide Y and [125I]neuropeptide Y-(2-36), adjacent
      sections were labeled and the binding sites detected by autoradiography. A
      similar distribution of binding was observed for each radioligand in all regions
      examined. Therefore, neuropeptide Y-(2-36) binds non-selectively to neuropeptide
      Y Y1 and neuropeptide Y Y2 receptors, but with lower affinity than neuropeptide Y
      and peptide YY. The increased potency and selectivity seen with neuropeptide Y-(2
      36) in feeding studies cannot be explained on the basis of a unique in vitro
      pharmacology.

PMID- 9016920
TI  - The effect of 5-HT1A receptor stimulation on nociceptive dorsal horn neurones in
      rats.
AB  - Spinal 5-HT1A receptor subtypes are involved in regulation of nociception. This
      study was performed to investigate the effect of stimulation of these receptors
      on wide dynamic range neurones in the spinal cord. Extracellular single unit
      recordings of dorsal horn neurones were performed in intact urethane
      anaesthetized female Sprague-Dawley rats. The receptive field distally on one
      hind paw was electrically stimulated with needle electrodes applied to the skin.
      The 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) ,
      and the 5-HT1A receptor antagonist, WAY100635 (N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl ]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride), were
      applied directly onto the spinal cord, and single unit responses were counted
      separately for Abeta-, Adelta-, C-fibre responses and post-discharge according to
      the latencies. Only 500 nmol 8-OH-DPAT caused a significant inhibition of all the
      neuronal responses. Cells with a pronounced wind-up, limited C-fibre response
      before drug application and relatively large receptive field for pinch in laminae
      III-IV were most powerfully inhibited by 500 nmol 8-OH-DPAT. 50 nmol WAY100635
      alone did not affect the neuronal responses but blocked the effect of 500 nmol 8
      OH-DPAT. These results suggest that stimulation of 5-HT1A receptors inhibits the
      activity in spinal wide dynamic range neurones after repeated electrical
      stimulation.

PMID- 9016921
TI  - Repeated cocaine exposure attenuates the ability of 5-hydroxytryptamine to
      release striatal dopamine in vivo.
AB  - Cocaine was administered repeatedly to rats and striatal microdialysis performed
      1, 7, 14, or 21 days after the last cocaine injection. Local perfusion of 10
      microM serotonin (5-hydroxytryptamine, 5-HT) increased basal dopamine levels
      approximately 7-fold (664 +/- 79%, 813 +/- 104% and 669 +/- 22%, n = 6, P <
      0.0001) in saline-treated controls, whereas in cocaine-treated animals the effect
      was significantly attenuated (432 +/- 55%, 465 +/- 61% and 497 +/- 48% n = 6-10,
      P < 0.03) at 1, 7 and 14 days of withdrawal. The 5-HT effect on dopamine release
      returned to control levels 21 days after cocaine exposure and was not altered by
      acute cocaine treatment (30 mg/kg, i.p. 24 h prior). The results suggest that
      repeated cocaine administration attenuates the effectiveness of 5-HT on striatal
      dopaminergic activity.

PMID- 9016922
TI  - Tranilast suppresses the vascular intimal hyperplasia after balloon injury in
      rabbits fed on a high-cholesterol diet.
AB  - Intimal hyperplasia is a serious problem after percutaneous transluminal coronary
      angioplasty. In this study, we assessed the effect of tranilast on vascular
      intimal hyperplasia after balloon injury in rabbits fed on a high-cholesterol
      diet. In this animal model, intimal hyperplasia more severe than that in rabbits
      fed on a normal diet was observed. In addition, medial thickening and lipid
      deposits in both media and intima were also noted. These findings indicate that
      balloon injury caused intimal and medial hyperplasia and that this hyperplasia
      was accelerated by the high cholesterol load. Tranilast (300 mg/kg) significantly
      decreased the intimal area, medial area, and stenosis ratio, and increased the
      luminal/total area ratio, in the cholesterol-fed rabbits. These results suggest
      that tranilast may be useful for prevention of restenosis after percutaneous
      transluminal coronary angioplasty of patients, including those with a clinical
      risk of hypercholesterolemia.

PMID- 9016923
TI  - Antiarrhythmic effects of an aconitine-like compound, TJN-505, on canine
      arrhythmia models.
AB  - We examined the effects of an aconitine-like compound, TJN-505 (1alpha-16beta
      dimethoxy-20-ethyl-14alpha-(4-methox ybenzoyloxy)-aconitan-8,13-diol
      hydrochloride), on canine arrhythmias provoked by digitalis, two-stage coronary
      ligation, adrenaline, programmed electrical stimulation, or aconitine. TJN-505 (2
      2.5 mg/kg i.v.) suppressed digitalis-, two-stage coronary ligation- and
      adrenaline-induced ventricular arrhythmias. The antiarrhythmic plasma
      concentrations (IC50) of TJN-505 for these arrhythmia models were 1.26, 0.94 and
      1.31 microg/ml, respectively. TJN-505 (2 mg/kg i.v. followed by the infusion of
      0.1 mg/kg per min) prolonged PR, QRS, QTc and JTc intervals and the ventricular
      effective refractory period and reduced the incidence of programmed electrical
      stimulation-induced arrhythmias in dogs with 7-day-old myocardial infarction (P <
      0.05). TJN-505 (2 mg/kg i.v.) also suppressed the aconitine-induced atrial
      arrhythmias. In conclusion, TJN-505 suppressed various canine ventricular and
      atrial arrhythmias and seems to act as a blocker of multiple channels.

PMID- 9016924
TI  - In vitro pharmacological characterization of a new selective angiotensin AT1
      receptor antagonist, UR-7280.
AB  - UR-7280 (3-tert-butyl-1-propyl-5-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-y
      l]methyl]-1H-pyrazole-4-carboxylic acid) is a new and potent angiotensin AT1
      selective receptor antagonist. Binding studies in rat liver membranes showed that
      UR-7280 is an apparently competitive antagonist. However, in rabbit aorta this
      compound antagonized the angiotensin II-induced contractile response in an
      insurmountable way, causing a significant reduction of the maximal response.
      Additional binding studies evidenced that UR-7280 has a slowly reversible binding
      profile, consistent with its functional properties in rabbit aorta. The results
      obtained with a series of structural analogues of UR-7280 demonstrated a
      relationship between the size of the pyrazole 3-substituent and the surmountable
      or insurmountable mode of antagonism, indicating that this position may play a
      key role in the interaction between the antagonist and the angiotensin AT1
      receptor.

PMID- 9016925
TI  - Force-frequency response in isoproterenol-induced hypertrophied rat heart.
AB  - Rate-dependent force production was investigated using small trabecular muscle
      from control and hypertrophied rat cardiac muscle. Cardiac hypertrophy was
      induced by daily subcutaneous injection of isoproterenol (0.3 mg/kg body weight)
      for 12 days. The force-frequency relationship, for the control rat myocardium, is
      clearly biphasic. A stepped increase in stimulation frequency from 0.1 to 0.5 Hz
      results in a decrease in contractile force (negative phase). However, at higher
      stimulation frequency above 0.5 Hz, an increased contractile force is revealed
      (positive phase). Membrane action potential duration (APD50) was used to reflect
      sarcolemmal Ca2+ influx. The frequency-dependent increase in APD50 and the
      ability of nifedipine, a sarcolemmal L-type Ca2+ channel blocker, to eliminate
      the positive-force frequency response, indicate that sarcolemmal Ca2+ influx is
      important for force development at high stimulation frequency. Relative Ca2+
      content of sarcoplasmic reticulum is estimated from rapid cooling contractures.
      The parallel change of rapid cooling contractures and twitch force suggests that
      the sarcoplasmic reticulum Ca2+ content alters with varying frequencies of
      stimulation. Isoproterenol-induced hypertrophied muscle shows a greater
      contractile force, increased nifedipine-sensitive force development and prolonged
      APD50 compared to controls. These data suggest a greater availability of
      intracellular Ca2+ to activate contraction in hypertrophied muscle, possibly by
      amplified Ca2+ influx via L-type channel.

PMID- 9016926
TI  - Structure-activity analysis for the effects of gamma-MSH/ACTH-like peptides on
      cerebral hemodynamics in rats.
AB  - In a previous structure-activity analysis we have shown that the gamma-melanocyte
      stimulating hormones (gamma-MSHs) and structurally related adrenocorticotropic
      hormone (ACTH) fragments share an amino-acid sequence which is determinant for
      the effects of these peptides on peripheral hemodynamics, viz. a pressor and a
      tachycardiac response, in conscious rats. We now investigated whether these
      structural features are also important for the effects of these peptides on
      cerebral hemodynamics in urethane-anesthetized rats. After intracarotid and
      intravenous administration, the 'mother' peptides, Lys-gamma2-MSH and gamma2-MSH,
      and, with a 10-fold lower potency, ACTH-(4-10), caused a dose-dependent pressor
      and tachycardiac response, as well as an increase in extra- and intracranial
      blood flow and microcirculatory cerebrocortical blood flow. Removal of C-terminal
      amino acids resulted in gamma-MSH-fragments which were devoid of effects on
      peripheral and central hemodynamics. Fragments of gamma2-MSH which were shortened
      at the N-terminal side (gamma-MSH-(4-12) and gamma-MSH-(5-12)) were less potent
      than gamma2-MSH, but had an intrinsic activity similar to that of gamma2-MSH with
      respect to the pressor and tachycardiac effect. However, the potency and
      intrinsic activity of these shortened fragments on intracerebral hemodynamic
      parameters were the same as those of gamma2-MSH. This suggests that different
      mechanisms (e.g., site of action and/or melanocortin receptor subtype) are
      involved in the cerebral hemodynamic effects of the melanocortins and in their
      peripheral hemodynamic effects. Surprisingly, removal of an additional residue,
      His5, resulting in the fragment gamma-MSH-(6-12), led to full restoration of
      potency with respect to extracranial blood flow, blood pressure and heart rate.
      Neither the structurally related analog, [Nle4,D-Phe7]alpha-MSH (NDP-MSH), nor
      ACTH-(1-24) was able to induce a pressor effect or cerebral hemodynamic effects.
      In contrast, both compounds had a depressor effect. It is concluded that the C
      terminal amino acids in the structure of gamma-MSH/ACTH-like peptides are
      essential for efficacy for the central hemodynamic effects, i.e., the increase in
      intracerebral (microcirculatory) blood flow. However, in contrast to what holds
      for the peripheral hemodynamic features, the N-terminal sequence has hardly any
      influence on potency or efficacy. The results with NDP-MSH and ACTH-(1-24) and
      the other fragments lead us to postulate that it is not one of the five known
      subtypes of melanocortin receptors which mediates the hemodynamic effects of the
      melanocortins, but an additional, still unidentified subtype. A clue for the
      elucidation of such a receptor might be found in the structural features of gamma
      MSH-(6-12) that appear to be very important determinants for the effectiveness to
      alter peripheral and central hemodynamics.

PMID- 9016927
TI  - Effects of Ro 47-0203 and PD155080 on the plasma kinetics, receptor binding and
      vascular effects of endothelin in the pig.
AB  - The effects of the mixed endothelin ET(A)/endothelin ET(B) receptor antagonist Ro
      47-0203 (bosentan, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-( 2-methoxy -phenoxy)
      2,2'-bipyrimidin-4-yl] -benzenesulfonamide) and the selective endothelin ET(A)
      receptor antagonist PD155080 (sodium 2-benzo[1,3]dioxol-5-yl-3-benzyl-4-(4-me
      thoxy-phenyl)-4-oxobut+ ++-2-enoate) on plasma half-life and regional extraction
      of exogenous endothelin-1 as well as on the regional vascular effects of
      endothelin-1 were investigated in the pig in vivo. Bosentan but not PD155080 (5
      mg/kg, i.v. bolus, both drugs) increased the arterial plasma levels of endothelin
      1-like immunoreactivity. Neither of the drugs affected the plasma half-life of
      infused endothelin-1. In the spleen, both the extraction and vascular effects of
      exogenous endothelin-1 were attenuated by both bosentan and PD155080 whereas
      renal extraction and vascular effects in the kidney were unaffected by both
      drugs. In the lung, only bosentan decreased pulmonary extraction of endothelin-1.
      In conclusion, the bosentan-induced increase of circulating endothelin-1 seems to
      be related to blockade of endothelin-1 binding to endothelin ET(B) receptors.
      Blockade of these receptors does not influence the overall elimination of
      endothelin-1, however.

PMID- 9016928
TI  - Peripheral effects of three novel non-peptide tachykinin NK1 receptor antagonists
      in the anaesthetized rat.
AB  - Three novel non-peptide tachykinin NK1 receptor antagonists were assessed on the
      transient fall in mean arterial blood pressure and the salivation induced by i.v.
      substance P (0.65 nmol/kg) in the urethane-anaesthetized rat. LY303241 ((R)-1-[N
      (2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4- phenylpiperazin-1
      yl)acetyl)amino]propane), LY303870 ((R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H
      indol-3-yl)-2-[N-(2-(4-(++ +piperidin-1 -yl)piperidin-1-yl)acetyl)amino]propane)
      and LY306740 ((R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4
      -cyclohexylpiperazin-1-yl)acetyl)amino]propane) (65 nmol-9 micromol/kg i.v.; 5
      min earlier) inhibited both the vasodepressor and salivary responses to substance
      P in a dose-dependent manner. LY303241 and LY306740 were more potent in
      inhibiting the vascular response to substance P while LY303870 was more potent in
      inhibiting the salivary response. LY303870 and LY306740 were devoid of direct
      effects while LY303241 decreased blood pressure and heart rate for 1 and 10 min,
      respectively. The antagonists act in a stereoselective and specific manner since
      the opposite (S) enantiomers of LY303870 (LY306155) and LY306740 (LY307679)
      failed to block the effects of substance P. In addition, LY303241, LY303870 and
      LY306740 neither affected the hypotension and the salivation induced by carbachol
      nor the increases in mean arterial pressure and heart rate induced by the
      tachykinin NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10). Only LY303241
      attenuated the decreases in mean arterial pressure and heart rate evoked by the
      tachykinin NK3 receptor agonist senktide. LY303870 and LY306740 appear to be the
      most interesting antagonists since they act in a specific and selective manner at
      the tachykinin NK1 receptor. The difference in the order of potency of the three
      antagonists to inhibit the hypotension and salivation elicited by substance P
      could be ascribed to their pharmacodynamic features or to the existence of
      different signal transduction mechanisms or receptor subtypes.

PMID- 9016929
TI  - Altered vasodilator response of coronary microvasculature in pacing-induced
      congestive heart failure.
AB  - To characterize vasodilator capacity of small coronary arteries (200-350 microm
      diameter) in the setting of congestive heart failure, we examined relaxation
      responses to acetylcholine (10(-9)-10(-4) M) and nitroglycerin (10(-9)-10(-4) M),
      in the absence and presence of the nitric oxide precursor, L-arginine (10(-4) M).
      Congestive heart failure was reliably induced in dogs by rapid ventricular pacing
      (250 beats.min(-1) for 4 weeks). Maximum relaxations (means +/- S.E.) to each
      vasodilator are expressed as a percentage of the relaxation response to
      papaverine (10(-4) M). Relaxation responses to the endothelium-dependent relaxing
      agent, acetylcholine, were not altered at heart failure, or in the presence of L
      arginine. Contrary to acetylcholine, relaxations to nitroglycerin were
      significantly enhanced in heart failure compared to control (83 +/- 25% vs. 25 +/
      6%, respectively, P < 0.05). Although L-arginine, alone, did not cause any
      vasodilator response in coronary microvessels, it was able to potentiate
      nitroglycerin relaxations at control (no L-arginine: 25 +/- 6% vs. L-arginine:
      135 +/- 66%). In contrast, at heart failure, L-arginine diminished nitroglycerin
      relaxations (no L-arginine: 83 +/- 25%, vs. L-arginine: 48 +/- 15%). These data
      indicate a unique vasodilator profile in small coronary arteries at heart
      failure: endothelium-dependent relaxations are unaltered, whereas responses to
      nitroglycerin are augmented. Addition of the nitric oxide precursor, L-arginine,
      did not affect acetylcholine relaxation, yet surprisingly had a differential
      effect in response to nitroglycerin. Moreover, inhibition of nitric oxide
      synthase with N(omega)-nitro-L-arginine elicited concentration-dependent
      constriction in heart failure but not control coronary microvessels. In summary,
      our study suggests an important role for nitric oxide in vasodilator control of
      coronary microvessels, which may modify nitrovasodilator therapy in congestive
      heart failure.

PMID- 9016930
TI  - Characterization of histamine receptors in the ureter of the dog.
AB  - We investigated the effects of histamine on the motility of isolated segments
      from canine ureters and characterized pharmacologically the histamine receptors
      involved. We also evaluated the effects of various autacoids (5-HT, carbachol,
      noradrenaline, thromboxane, prostaglandin F2alpha) on the motility of canine
      ureters. Histamine as well as the H1 receptor agonist 2-(2-pyridyl)ethylamine
      elicited a concentration-dependent contraction. This contractile response was
      antagonized by dimethindene, causing a rightward shift (pA2 8.30) and a reduction
      of the slope and the maximal effect (pD'2 6.01) of the concentration-response
      curve. The histamine H2 receptor antagonist cimetidine in a concentration of 10(
      5) mol/l was ineffective concerning the concentration-response curve for
      histamine. After precontraction of the ureter segments (5-HT, carbachol,
      prostaglandin F2alpha), a concentration-dependent relaxant effect was evaluated
      in the presence of histamine or the histamine H2 receptor agonist impromidine.
      The histamine H2 receptor antagonist cimetidine attenuated the relaxant response,
      causing a rightward shift of the concentration-response curve. All autacoids
      except thromboxane were capable of increasing contractility in canine ureters.
      Comparing the absolute contractile force in the presence of prostaglandin
      F2alpha, 5-HT, carbachol, noradrenaline and potassium, we found that histamine
      exhibits the most marked effect on this parameter in the canine ureter. It is
      concluded that there are two types of histamine receptors modulating contractile
      activity in the canine ureter: histamine H1 receptors, which mediate contraction,
      and histamine H2 receptors, which mediate relaxation (in the precontracted
      tissue).

PMID- 9016931
TI  - Characterization of the contractile response induced by 5-methoxytryptamine in
      rat stomach fundus strips.
AB  - This study examined effects of 5-methoxytryptamine (5-MOT), an agonist at 5-HT4
      and 5-HT2B receptors, on the contractile response and acetylcholine release in
      rat stomach fundus strips. 5-MOT (10(-9)-10(-5) M) produced a concentration
      dependent increase in the contraction, while it evoked acetylcholine release in a
      'bell-shaped' concentration-dependent manner. Atropine reduced 5-MOT (10(-8)-10(
      6) M)-induced contractions, but it had little effect on the contractions evoked
      by higher concentrations. 5-MOT-induced contraction and acetylcholine release
      were inhibited by SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2
      [diethylamino] ethyl ester), a 5-HT4 receptor antagonist. In the presence of
      atropine, both SDZ 205-557 and yohimbine, a 5-HT2B receptor antagonist, inhibited
      the contraction. In the presence of tetrodotoxin, the contraction was inhibited
      by yohimbine, but not by SDZ 205-557. These results suggest that the contractile
      action of 5-MOT in rat stomach fundus involves atropine-sensitive and atropine
      resistant components. The sensitive contraction appears to be mediated through 5
      HT4 receptors located on cholinergic neurons, whereas the resistant contraction
      is mediated through 5-HT4 receptors located on non-cholinergic neurons and
      through 5-HT2B receptors.

PMID- 9016932
TI  - Developmental changes in sympathetic contraction of the circular muscle layer in
      the guinea-pig vas deferens.
AB  - Contractile responses of the circular muscle of the isolated vas deferens to
      electrical stimulation (10-80 Hz) and to noradrenaline significantly decreased
      with increasing age in 3-week-, 10-week- and 18-month-old guinea pigs, observed
      by the cannula insertion method. There were no significant differences in the
      contractile responses induced by alpha,beta-methylene ATP or BaCl2 between 3 and
      10 weeks old, but the responses to alpha,beta-methylene ATP or BaCl2 decreased in
      18-month-old guinea pigs. The contractile response to electrical stimulation was
      monophasic in 3-week-old guinea pigs, a small portion of which remained after the
      treatment with prazosin. Desensitisation of P2X-purinoceptors with alpha,beta
      methylene ATP significantly inhibited the contractile responses to stimulation
      with relatively low frequencies, and the combination of both prazosin and
      alpha,beta-methylene ATP abolished the stimulation-induced contractions. In 10
      week- and 18-month-old guinea pigs electrical stimulation evoked a transient
      contraction followed by a second contraction at the offset of the stimulation
      (the after-response). The after-responses were blocked by prazosin. These results
      show that the dominant component of sympathetic cotransmission is noradrenaline;
      a purinergic component also exists in the sympathetic contraction in the circular
      muscle of the vas deferens in young guinea pigs, but is virtually absent in the
      later stages of development. The sympathetic contractions of the circular muscles
      significantly decrease with increasing age and this appears to be due to changes
      in postjunctional, rather than prejunctional, mechanisms.

PMID- 9016933
TI  - Characterization of tachykinin NK2 receptor on dog proximal colon. Antagonism by
      MEN 10,627 and SR 48,968.
AB  - The nature of the tachykinin receptors involved in the contraction of the
      circular muscle of dog colon has been investigated. The following rank order of
      potency for agonists was obtained: [Sar9,Met(O2)11]substance P > or = neurokinin
      A > [beta-Ala8]neurokinin A-(4-10) >> [MePhe7]neurokinin B. The efficacy of the
      tachykinin NK2 receptor agonists was significantly greater than that of the
      tachykinin NK1 receptor agonists and of carbachol. A concentration-dependent
      rightward shift of the motor response to neurokinin A (obtained in the presence
      of (+/-)-CP 96,345) was induced by peptide and non-peptide tachykinin NK2
      receptor antagonists with this rank order: MEN 10,627 = SR 48,968 >> L 659,877 >
      MEN 10,376 > MDL 28,564. MEN 10,627 and SR 48,968 affinities were similar to
      those measured in human tissues. In conclusion, the tachykinin NK2 receptor plays
      a predominant role in tachykinin-induced contraction of the canine colonic
      circular muscle and this tissue could be useful to predict the pharmacological
      actions of MEN 10,627 and SR 48,968 in human colon.

PMID- 9016934
TI  - Characterisation of the 5-HT receptor potentiating neurotransmission in rabbit
      bladder.
AB  - We have investigated the effects of 5-hydroxytryptamine (5-HT) on electrically
      induced contractions of rabbit isolated bladder. Electrical field stimulation
      evoked twitch contractions which were potentiated by 5-HT (0.3-10 microM). The
      potentiating effect of 5-HT was inhibited by ondansetron (pA2 9.2) and
      granisetron (pA2 9.1) but not by methysergide or SB 204070 ((1-butyl-4
      piperidinyl)methyl 8-amino-7-chloro-1,4-benzodioxan-5-carboxylate hydrochloride).
      This suggests that the potentiating effect of micromolar concentrations of 5-HT
      on neuromuscular transmission in rabbit isolated bladder is mediated by 5-HT3
      receptors. The receptors involved in the response to lower concentrations of 5
      HT, observed in some tissues, remain to be characterised.

PMID- 9016935
TI  - Glucagon-like peptide-1-(9-36) amide is a major metabolite of glucagon-like
      peptide-1-(7-36) amide after in vivo administration to dogs, and it acts as an
      antagonist on the pancreatic receptor.
AB  - This study assesses the importance of metabolites formed following exogenous
      administration of glucagon-like peptide-1-(7-36) amide (GLP-1). After
      subcutaneous (s.c.) administration of GLP-1 to dogs the plasma immunoreactivity
      of GLP-1 measured by two different radioimmunoassays (RIAs) were higher than that
      measured by a sandwich enzyme-linked immunosorbent assay (ELISA). This
      discrepancy was due to the formation of the metabolites GLP-1-(9-36) amide, GLP-1
      (7-35) and GLP-1-(7-34). Receptor binding studies using baby hamster kidney cells
      expressing the human pancreatic GLP-1 receptor showed that the affinity of GLP-1
      (9-36) amide, GLP-1-(7-35) and GLP-1-(7-34) was 0.95%, 12% and 2.8%,
      respectively, of the affinity of GLP-1-(7-36) amide. Furthermore, GLP-1-(9-36)
      amide was shown to be an antagonist to adenylyl cyclase activity, whereas GLP-1
      (7-35) and GLP-1-(7-34) were shown to be agonists. GLP-1-(9-36) amide was shown
      to be present in vivo in amounts up to 10-fold that of GLP-1-(7-36) amide. Due to
      its low binding affinity, this antagonistic metabolite does not seem to be able
      to cause physiological antagonism upon s.c. administration of the peptide.

PMID- 9016936
TI  - Potential role of the autonomic nervous system in the immunosuppressive effects
      of acute morphine administration.
AB  - These studies investigated the role of the autonomic nervous system in mediating
      the immunosuppressive effect of morphine on blood lymphocyte proliferation in
      rats. To determine the contribution of the autonomic nervous system, rats were
      pretreated with the ganglionic blocker chlorisondamine (5 mg/kg) prior to
      morphine (7 mg/kg) administration. Ganglionic blockade with chlorisondamine
      completely antagonized the inhibitory actions of morphine, suggesting that intact
      ganglionic transmission was required for the inhibition to occur. Blockade of
      postganglionic parasympathetic neurotransmission with atropine methylbromide (1
      mg/kg) or blockade of sympathetic neurotransmission with the alpha-adrenoceptor
      antagonist phentolamine (1 mg/kg) did not attenuate the suppressive effect of
      morphine. Blockade of beta-adrenoceptors with propranolol (2.5 mg/kg) resulted in
      partial antagonism, but this action was not shared by the peripherally acting
      beta-adrenoceptor antagonist nadolol (6 mg/kg). These results suggest that the
      inhibitory effect of morphine on blood lymphocyte proliferation may be mediated
      through activation of the autonomic nervous system; however, individual blockade
      of either the parasympathetic or sympathetic division of the autonomic nervous
      system was not sufficient to antagonize this immunosuppressive effect.

PMID- 9016937
TI  - Suplatast tosilate, a new type of antiallergic agent, prevents the expression of
      airway hyperresponsiveness in guinea pigs.
AB  - Suplatast tosilate (suplatast) is an antiallergic agent capable of down
      regulating the functions of CD4+ T cells. We now investigated the effects of
      suplatast on the antigen-induced airway hyperresponsiveness and the underlying
      allergic inflammatory response in sensitized guinea pigs. Animals that had been
      immunized twice by ovalbumin inhalation on day 0 and day 7 developed an increased
      airway responsiveness against inhaled acetylcholine 24 h after the ovalbumin
      challenge on day 14. Suplatast (10 and 100 mg/kg per day) and ketotifen (10 mg/kg
      per day) given orally from day 0 to day 14 effectively inhibited the expression
      of airway hyperresponsiveness. They also inhibited the infiltration of
      eosinophils and macrophages into broncho-bronchiolar walls and lumen.
      Interestingly, suplatast, but not ketotifen, inhibited the infiltration of
      lymphocytes including CD4+ T cells. Collectively, these results strongly suggest
      that suplatast prevents the expression of airway hyperresponsiveness due to the
      ability to suppress the infiltration of inflammatory cells into lung tissues.

PMID- 9016938
TI  - Nucleoside transporter-mediated uptake and release of [3H]L-adenosine in DDT1 MF
      2 smooth muscle cells.
AB  - [3H]L-Adenosine, an enantiomer of the physiological D-adenosine, was shown
      previously to be taken up and released, at least in part, through nucleoside
      transporters in rat brain preparations. In the present study, we used clonal
      smooth muscle DDT1 MF-2 cells that contain almost exclusively equilibrative
      inhibitor-sensitive (es) nucleoside transporters to test the hypothesis that L
      adenosine is a permeant for these bidirectional nucleoside transporters. DDT1 MF
      2 cells accumulated approximately 3 times more [3H]D- than [3H]L-adenosine; 10
      microM nitrobenzylthioinosine significantly (P < 0.01) inhibited the accumulation
      of [3H]D-adenosine by 86% and of [3H]L-adenosine by 63%. The IC50 values for the
      nitrobenzylthioinosine-sensitive portions of [3H]L- and [3H]D-adenosine
      accumulation were 1.6 and 2.0 nM, respectively. [3H]D-Adenosine accumulation was
      significantly (P < 0.05) inhibited by up to 72% with L-adenosine and [3H]L
      adenosine accumulation was significantly (P < 0.01) inhibited by up to 52% with D
      adenosine. Release of accumulated [3H]L-adenosine was temperature- and time
      dependent, and was significantly (P < 0.05) reduced by 47% with dipyridamole, 39%
      with dilazep, and 45% with nitrobenzylthioinosine; the apparent IC50 value for
      nitrobenzylthioinosine was < 1 nM. These data indicate that a significant
      proportion of [3H]L-adenosine uptake and release in DDT1 MF-2 cells is mediated
      by es nucleoside transporters.

PMID- 9016939
TI  - On the mechanism of the differential effects of NS004 and NS1608 in smooth muscle
      cells from guinea pig bladder.
AB  - Our recent study revealed that the reported BK(Ca) channel openers NS004 (5
      trifluoromethyl-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-2H-benzimidazo le-2-one)
      and its analog NS1608 (N-(3-(trifluoromethyl)phenyl)-N'-(2-hydroxy-5
      chlorophenyl)urea) produced a differential pattern of action on the BK(Ca)
      channel in porcine coronary arterial cells (Hu, S., H.S. Kim and C.A. Fink, 1995,
      Differential effects of the BK(Ca) channel openers NS004 and NS1608 in porcine
      coronary arterial cells, Eur. J. Pharmacol. 294, 357). In this study, using the
      patch-clamp method on the smooth muscle cells from guinea pig bladder detrusor,
      the activity profile of NS004 and NS1608 on the whole-cell BK(Ca) current (I(BK))
      was examined and found to be similar to that in coronary arterial cells. NS004
      did not significantly modify I(BK) at concentrations below 5 microM, but robustly
      augmented I(BK) at concentrations greater than 20 microM. With a minimum
      effective concentration of 0.5 microM, NS1608 caused potentiation of I(BK) with a
      bell-shaped concentration-response relationship. The activation was maximized
      between 5-10 microM and substantially attenuated at higher concentrations. The
      behavior of single BK(Ca) channels in the presence of NS004 and NS1608 was
      scrutinized to elucidate the mechanism underlying their distinct patterns of
      action. The channel open-state probability (NPo) was increased by NS004 at 0.5, 5
      and 50 microM to a respective 1.75 +/- 0.38, 4.05 +/- 0.90, and 15.01 +/- 3.66
      fold (n = 7) of the control by increasing the open time and the frequency of
      opening while having no effect on the single BK(Ca) channel conductance. NS1608
      at 0.5 and 5 microM increased NPo to 1.69 +/- 0.43 and 18.03 +/- 6.64 fold of the
      control (n = 4), respectively. NS1608 at higher concentrations repeatedly blocked
      channel openings as evidenced by the highly flickering open state, though the
      overall open time and frequency of opening remained high. The diminished
      activation of I(BK) by 50 microM NS1608 manifested therefore a net result of
      these two opposing actions on the single channels. Thus, the two structurally
      related BK(Ca) channel openers interact distinctly with the channel gating
      components.

PMID- 9016940
TI  - Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid
      isolated from Evodia rutaecarpa.
AB  - In this study, rutaecarpine was tested for its antiplatelet activities in human
      platelet-rich plasma. In human platelet-rich plasma, rutaecarpine (40-200 microM)
      inhibited aggregation stimulated by a variety of agonists (i.e., collagen, ADP,
      adrenaline and arachidonic acid). The antiplatelet activity of rutaecarpine (120
      microM) was not significantly attenuated by pretreatment with the nitric oxide
      synthase inhibitor N(G)-mono-methyl-L-arginine (L-NMMA) (100 microM) or N(G)
      nitro-L-arginine methyl ester (L-NAME) (200 microM) and with the guanylyl cyclase
      inhibitor methylene blue (100 microM). In addition, rutaecarpine (40-200 microM)
      did not significantly affect cyclic AMP and cyclic GMP levels in human washed
      platelets, whereas it significantly inhibited thromboxane B2 formation stimulated
      by collagen (10 microg/ml) and thrombin (0.1 U/ml). Furthermore, rutaecarpine (40
      200 microM) inhibited [3H]inositol monophosphate formation stimulated by collagen
      and thrombin in [3H]myoinositol-loaded platelets. It is concluded that the
      antiplatelet effects of rutaecarpine are due to inhibition of thromboxane
      formation and phosphoinositide breakdown.

PMID- 9016941
TI  - Synthesis of glucose-chlorambucil derivatives and their recognition by the human
      GLUT1 glucose transporter.
AB  - A limitation of the use of chemotherapeutic agents against intracerebral tumors
      lies on their poor uptake into the central nervous system. An approach to enhance
      brain delivery is to design agents that are transported into the brain by one of
      the saturable nutrient carriers of the blood-brain barrier, the highly efficient
      brain and erythrocyte glucose transporter isoform GLUT1. Since the GLUT1 hexose
      transporter of the blood-brain barrier is also present on erythrocytes, new
      compounds designed to be transported by the GLUT1 transporter were studied on
      human erythrocytes, which represent unique, easily accessible human GLUT1
      expressing cells. In this paper we describe the synthesis of four glucose
      chlorambucil derivatives, namely methyl 6-O-4[bis(2-chloroethyl)amino]benzenebut
      anoyl-beta-D-glucopyranosi de (3), 6-O-4-[bis(2-chloroethyl)amino]benzenebu
      tanoyl-D-glucopyranose (6), methyl 6-[4-[bis(2-chloroethyl)amino]benzenebut
      anoylamido]-6-deoxy-beta-D-glucopyranoside (9) and 6-[4-[bis(2
      chloroethyl)amino]benzenebut anoyl amido]-6-deoxy-D-glucopyranose (10), and the
      study of their interactions with the GLUT1 transporter of the human erythrocytes.
      All four compounds were able to inhibit [14C]glucose uptake in a concentration
      dependent manner. One of them, compound 6, exhibited an approximately 160-fold
      higher inhibition of [14C]glucose uptake by the GLUT1 transporter than glucose
      itself. Compound 6 was also able to inhibit [3H]cytochalasin B binding to
      erythrocytes with approximately 1000-fold higher efficacy than does glucose. The
      inhibition of glucose uptake was entirely reversible, indicating that it was not
      due to alkylation of a nucleophilic group of the hexose transporter. The above
      results suggested specific interactions of compound 6 with the hexose transporter
      protein. Uptake studies of [14C]compound 6 indicated, in addition, some non
      specific interactions with intact and open erythrocyte membranes: only a small
      amount of the bound [14C]compound 6 can be displaced by cytochalasin B.
      Collectively, these findings led us to conclude that the interactions of compound
      6 with GLUT1 are presumably that of a non-transported inhibitor.

PMID- 9016943
TI  - Acute or prolonged exposure to 1-aminocyclopropanecarboxylic acid protects spinal
      neurons against NMDA toxicity.
AB  - 1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity partial agonist for
      the glycine binding site within the NMDA receptor complex. Chronic treatment with
      ACPC in vivo appears to reversibly desensitize the NMDA receptor complex,
      prompting suggestions that it might provide an effective means of ameliorating
      degenerative mechanisms mediated through this ligand-gated ion channel. In the
      present experiments, cultured rat spinal cord neurons were used to further
      examine the effects of acute and sustained ACPC exposures on N-methyl-D-aspartate
      (NMDA)-induced neurotoxicity. Cell damage was quantitatively assessed using a
      tetrazolium salt colorimetric assay. With coincubation, 1 mM ACPC significantly
      reduced the neuronal cell damage caused by 30 min exposure to 25 or 50 microM
      concentrations of NMDA, but, in contrast to other competitive and non-competitive
      NMDA receptor antagonists (D-(-)-2-amino-5-phosphonovaleric acid (APV),
      dizocilpine maleate (MK-801) and 7-chlorokynurenic acid (7-CK)), it failed to
      alter the cell injury induced by 100 microM NMDA. The protective effect of ACPC
      was competitively abolished by coaddition of glycine, verifying that it was
      mediated through glycine binding sites. Sustained 20 h exposure to 1 mM ACPC
      (which was removed 30 min before addition of 25 microM NMDA) also caused cells to
      be significantly less responsive to the neurotoxic effects of NMDA. Pre-exposure
      to ACPC for shorter intervals ( < 1 h) failed to alter subsequent NMDA toxicity.
      Acute or sustained exposures to ACPC alone did not affect cell viability. These
      results support earlier indications that: (1) ACPC provides an effective means of
      antagonizing excitotoxic phenomena, and (2) sustained exposure to ACPC
      desensitizes the NMDA receptor complex.

PMID- 9016942
TI  - The neuropeptide Y Y1 receptor selective radioligand, [125I][Leu31,Pro34]peptide
      YY, is also a high affinity radioligand for human pancreatic polypeptide 1
      receptors.
AB  - A number of receptors for the pancreatic polypeptide-fold peptides are proposed
      based on findings from pharmacology and molecular biology studies. Neuropeptide Y
      and peptide YY have similar affinity for neuropeptide Y Y1 and neuropeptide Y Y2
      while pancreatic polypeptide has highest affinity for pancreatic polypeptide 1.
      Pro34-substituted analogs of neuropeptide Y and peptide YY have selectivity for
      neuropeptide Y Y1 over neuropeptide Y Y2 receptors. In the present study, we
      found that one such 'neuropeptide Y Y1-selective' radioligand,
      [125I][Leu31,Pro34]peptide YY, also binds with high affinity to the pancreatic
      polypeptide 1 receptor. Therefore, caution needs to be exercised when using Pro34
      analogs to define the neuropeptide Y Y1 receptor in vivo and using tissue
      preparations.

PMID- 9016944
TI  - Evidence for receptor subtype cross-talk in the mitogenic action of serotonin on
      human small-cell lung carcinoma cells.
AB  - We previously reported a significant mitogenic effect of serotonin (5
      hydroxytryptamine, 5-HT) on human small-cell lung carcinoma cells (SCLC, GLC-8),
      mediated by both 5-HT1D and 5-HT1A receptors. Here we investigate possible
      interactions between the two receptor subtypes. Dose-effect curves obtained by
      simultaneously applying equipotent concentrations of the selective 5-HT1A agonist
      8-OH-DPAT and the selective 5-HT1D receptor agonist sumatriptan are shifted to
      the right, although maximal effects are additive. The nonselective 5-HT
      antagonist metergoline displays higher potency when both receptor subtypes are
      activated. The 5-HT1D receptor antagonist GR127935 is markedly more potent
      against sumatriptan than against the sensitive portion of 5-HT effect. Indeed,
      both GR127935 and the 5-HT1A antagonist spiperone shift the EC50 for the residual
      effect of 5-HT from approximately 300 to 120-150 nM, suggesting that blocking one
      receptor subtype may facilitate activation of the other. Preincubation with
      either 8-OH-DPAT or sumatriptan suppresses the mitogenic response to the other
      specific receptor agonist; suppression is complete within 10 min at 37 degrees C,
      and is not observed when the preincubation is done at 4 degrees C. Measurements
      of adenylate cyclase activity do not help in interpreting the results.
      Conversely, measurements of MAP kinase activity reveals biphasic activation with
      a delayed activation at 1 h, and reproduce the suppression of the effect of the
      second drug by 15 min preincubation. These findings constitute the first evidence
      of a reciprocal negative interference between human 5-HT1A and 5-HT1D receptors,
      and indicate that SCLC GLC-8 cells simultaneously express both receptor subtypes.
      Mere reciprocal antagonism of the drugs employed cannot account for these data.
      We suggest that in this cell system cross-talk occurs in the transduction
      pathways of the two receptor subtypes.

PMID- 9016946
TI  - Toxoplasma gondii expresses two distinct lactate dehydrogenase homologous genes
      during its life cycle in intermediate hosts.
AB  - Two Toxoplasma gondii genes were characterized that are differentially expressed
      during the parasite's life cycle. The genes named LDH1 and LDH2, respectively,
      encode polypeptides similar to the enzyme lactate dehydrogenase (LDH; L
      lactate:NAD+ oxidoreductase, EC 1.1.1.27) from a variety of organisms. They show
      64.0% nucleotide identity in the coding region and both have an intron at the
      same relative position. The deduced amino acid sequences of LDH1 and LDH2 share
      71.1% identity. LDH1 and LDH2 are most similar to an LDH of Plasmodium falciparum
      (46.5% and 48.5% amino acid identities, respectively). The mRNA of LDH2 was only
      detected in the bradyzoite stage, while the mRNA of LDH1 was detected in both the
      bradyzoite and tachyzoite stages. However, by isoelectric focusing and immunoblot
      analysis, only one LDH isoform was found to be expressed in each stage.
      Furthermore, the expression of a reporter gene carrying chloramphenicol
      acetyltransferase (CAT) coding sequence and the putative LDH2 promoter sequence
      was significantly up-regulated by growing parasites in tissue culture in media
      with alkaline pH (pH 8.2, a condition known to induce the expression of
      bradyzoite-specific antigens), while the expression of a CAT reporter construct
      carrying the putative LDH1 promoter sequence was down-regulated by similar
      treatment. These results indicate that LDH expression is developmentally
      regulated in T. gondii and suggest a possible correlation between stage
      conversion and alteration in carbohydrate or energy metabolism in this parasite.

PMID- 9016945
TI  - Thermodynamics of ligand binding to the cloned delta-opioid receptor.
AB  - The goal of this study was to determine the relative contribution of entropy and
      enthalpy to the free energies of binding to recombinant mouse delta-opioid
      receptors for the peptide agonist, DPDPE ([D-Pen2,D-Pen5]enkephalin), the peptide
      antagonist, TIPP(psi) (Tyr-Tic(psi)[CH2NH]Phe-Phe-OH), the nonpeptide agonist,
      SNC80 ((+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl )-3
      methoxybenzyl]-N,N-diethylbenzamide), and the nonpeptide antagonist, naltrindole.
      Competitive binding studies were carried out using [3H]naltrindole at 0 degrees
      C, 12 degrees C, 25 degrees C and 37 degrees C, the affinities calculated and
      van't Hoff plots constructed for each ligand. The temperature dependence of
      binding and van't Hoff plots indicated that the entropy contribution is the major
      component of the free energy, for all four ligands, independent of its activity
      or chemical nature.

PMID- 9016947
TI  - Identification and chromosomal localization of a processed pseudogene of human
      GRK6.
AB  - G-protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G
      protein-coupled receptors, resulting in desensitization of receptor signaling. To
      date, 6 mammalian GRKs have been identified by molecular cloning. Several lines
      of evidence indicate that a homologue of GRK6, the most recently described GRK,
      is present in the human genome. Northern analysis identifies two transcripts
      which hybridize to GRK6, and genomic Southern analysis indicates that GRK6 is
      localized to chromosome 5, with a second GRK6-like locus on chromosome 13. To
      identify the GRK6 homologue on chromsome 13, several sets of closely-spaced
      primers were designed based on the GRK6 cDNA sequence and then used to amplify
      human genomic DNA by PCR. Two products were identified, the larger of which is a
      fragment of the GRK6 gene which contains introns, while the smaller fragment is
      94% homologous to GRK6 and contains no introns. In order to further characterize
      this GRK6 homologue, primers from the 5' and 3' coding regions of GRK6 were used
      to amplify a product of 1458 base pairs from human genomic DNA. This 1458 base
      pair PCR fragment displays 94% homology to GRK6 and contains multiple nucleotide
      insertions and deletions compared to GRK6, including a C to T mutation at base
      pair 202 which creates a predicted in-frame stop codon. In an effort to determine
      whether this gene is transcriptionally active, primers designed to preferentially
      amplify either GRK6 or the homologue were used in reverse transcription PCR. In
      contrast to the GRK6-specific primers, primers which selectively amplify the GRK6
      homologue fail to produce a PCR product in any RNA tested, indicating that this
      gene is most likely transcriptionally inactive. PCR amplification of rodent/human
      hybrid cell lines using these same primers confirms the previously established
      chromosome 5 localization of GRK6, and localizes this homologue to chromosome 13.
      Northern analysis indicates that the two GRK6-hybridizing species seen in RNA
      differ by approximately 500 base pairs in the 3' untranslated region, indicating
      that both transcripts likely arise from differential processing of a single gene.
      Taken together, these data indicate that the GRK6-hybridizing species on
      chromosome 13 is a transcriptionally inactive processed pseudogene of GRK6, while
      the two GRK6 transcripts differ in the 3' untranslated region.

PMID- 9016948
TI  - NF-Y binds to the inverted CCAAT box, an essential element for cAMP-dependent
      regulation of the rat fatty acid synthase (FAS) gene.
AB  - Using EMSA competition experiments together with supershifts and in vitro
      transcription/translation we show that the basal transcription factor NF-Y or a
      related factor binds to the cAMP-responsive inverted CCAAT box recently
      identified in the rat fatty acid synthase (FAS) gene from nucleotide -99 to -92
      relative to the transcription start site of the FAS mRNA. This result indicates a
      putative novel role for NF-Y in the cAMP-dependent gene regulation in a small
      class of genes such as FAS and tryptophan hydroxylase. Since NF-Y is a
      constitutively produced factor, not surprisingly, no differences in the specific
      DNA/protein complex with the CCAAT(FAS) box and nuclear proteins from H4IIE cells
      treated with cAMP and/or insulin or not could be observed. This implies that NF-Y
      might be modified in response to cAMP or might interact with another factor whose
      properties are altered by cAMP.

PMID- 9016949
TI  - Isolation of cDNAs encoding chicken homologues of the yeast SNF2 and Drosophila
      Brahma proteins.
AB  - The SNF2/Brahma proteins are a class of DNA-dependent ATPases which activate gene
      expression by disrupting chromatin repression. They also cooperate with nuclear
      hormone receptors to activate transcription. Two cDNAs encoding chicken
      homologues of the SNF2/Brahma proteins have been isolated from chicken
      haematopoietic libraries. The encoded proteins closely resemble the human
      homologues, hBRM and BRG1, and the chicken homologues have therefore been termed
      cBRH and cBRG1. Homology is conserved in five characteristic domains: an N
      terminal domain that binds the SNF11 protein, a conserved domain A of unknown
      function, a central ATPase domain, a domain that binds the retinoblastoma tumor
      suppressor protein Rb, and a C-terminal bromodomain of unknown function.

PMID- 9016950
TI  - Molecular analysis of a Penicillium chrysogenum GATA factor encoding gene (sreP)
      exhibiting significant homology to the Ustilago maydis urbs1 gene.
AB  - Employing a PCR-aided strategy, a Penicillium chrysogenum gene (sreP) encoding a
      putative GATA-transcription factor has been cloned and characterized. Comparison
      of the genomic and cDNA sequences revealed the presence of an open reading frame
      (ORF) encoding a protein of 532 amino acids (aa) which is interrupted by two
      introns. The deduced aa sequence of sreP reveals 50% identity to a regulator of
      siderophore biosynthesis (URBS1) from Ustilago maydis over a stretch of 200 aa
      containing two GATA-type zinc finger motifs and a Cys-rich intervening sequence.
      Northern blot analysis indicated two transcripts of 2.2 and 2.7 kb in
      approximately equivalent amount. due to two major transcription start sites.

PMID- 9016951
TI  - Use of an alternate splice donor site in the human GAP gene is responsible for
      synthesis of the p100 isoform.
AB  - GAP (GTPase-activating protein), a negative regulator of the receptor tyrosine
      kinase signal transduction pathway, exists as two isoforms: a ubiquitous, p120
      form and a primate placenta-specific p100 form lacking the N-terminal hydrophobic
      domain. The cDNA species encoding p120 and p100 GAP are identical except that
      p100 GAP cDNA contains a 65-bp insert not present in p120 cDNA. The purpose of
      this study was to locate the 65-bp insert in the genomic GAP sequence, thereby
      determining the mechanism by which alternate splicing produces the two mRNA
      species. It was found that the 65-bp insert is located just 3' to the sequence
      encoding the hydrophobic domain, indicating that the p100 form of GAP results
      from utilization of an alternate splice donor site. In addition, the sequence
      encoding the hydrophobic domain was found to be contained within a single large
      exon. The intron separating this exon from the exon encoding the 5'-portion of
      the SH2-N domain was determined to be at least 40 kb in length. Finally, it was
      found that the sequence encoding the SH2-N domain contains an intron 1006 bp
      long, and the sequence of this intron has been deduced. It is anticipated that
      the data presented in this paper will provide the basis for elucidating RNA
      processing mechanisms responsible for preferential expression of p100 GAP in the
      human placenta.

PMID- 9016952
TI  - Variation in the methylation profile and structure of Pax3 and Pax7 among
      different mouse strains and during expression.
AB  - Structural alterations within the myogenic and neurogenic developmental gene Pax7
      which involve TaqI recognition sequences have previously been reported. These
      alterations are associated with differences in the efficiency of regrowth of
      damaged skeletal muscle. To identify other structural features of Pax genes which
      may influence skeletal muscle regrowth, variation in the structure and
      methylation status of Pax7 and the closely related gene Pax3 has been sought
      among different mouse strains and during gene expression using the restriction
      endonucleases MspI and HpaII. Following MspI digestion, RFLPs within Pax7 have
      been found which most likely reflect intron size variability within the paired
      box. Differences in the size of MspI and HpaII fragments hybridising with Pax7
      and Pax3 region specific sub-probes indicate that the paired boxes are
      hypomethylated, whereas the region encoding the homeodomain of each gene is
      highly methylated in the spleen and other tissues from adult mice. In the
      skeletal muscle precursor cell line C2C12, which expresses Pax7 but not Pax3, the
      homeodomain encoding region of Pax7 is hypomethylated. In spleen cells, the Pax7
      paired box is transcribed but the homeodomain encoding region is not. By
      contrast, both the paired box and the homeobox of Pax3 are hypermethylated in
      C2C12 cells indicating that generation of alternate transcripts from Pax genes
      may be controlled by DNA methylation. In contrast to Pax3, reference to the size
      of fragments hybridising with a Pax7 homeobox specific probe provides evidence
      for CpNpG methylation within and immediately downstream from the region encoding
      the homeodomain. Interestingly, CpNpG methylation remains when the Pax7 homeobox
      is expressed. Structural variation recognised by MspI digestion and differences
      in the methylation profile of Pax7 are not associated with the ability to regrow
      damaged skeletal muscle.

PMID- 9016953
TI  - DNA sequence and secondary structure of the mitochondrial small subunit ribosomal
      RNA coding region including a group-IC2 intron from the cultivated basidiomycete
      Agrocybe aegerita.
AB  - Due to their structural complexity and their evolutionary dimension, rRNAs are
      the most investigated nucleic acids in prokaryotes, eukaryotes and organelles.
      However, no complete sequence of a mitochondrial small subunit (SSU) rRNA was
      available in the basidiomycotina subdivision. The mitochondrial gene encoding the
      SSU rRNA of the cultivated basidiomycete Agrocybe aegerita was cloned and its
      complete nucleotide sequence achieved; the 5'- and 3'-ends were localized by
      nuclease SI mapping, leading to a size of 3277 nt. The secondary structure of the
      SSU rRNA (1906 nt in size) possessed all the helices and loops of the prokaryotic
      model; a unique modification was found in a conserved nucleotide predicted by the
      model: the nt 487 was A instead of C. The same modification, has been found in
      all the partial basidiomycete mitochondrial sequences available in databases. The
      Agrocybe aegerita SSU rRNA was characterized by large and unusual extensions
      leading to additional helices in the variable domains V4, V6 and V9, which were
      the longest of the known prokaryotic or mitochondrial SSU rRNAs. Nucleotide
      sequence analysis indicated a 1371-bp intron, belonging to subgroup-IC2, located
      in a conserved loop in the 3'-part of the SSU rRNA. This intron, which is the
      second example reported in a fungal mitochondrial SSU rDNA, encoded a putative
      protein (407 aa) sharing homologies with endonucleases involved in group-I intron
      mobility. This report constitutes the first complete mitochondrial SSU rRNA
      sequence and secondary structure of any member of the basidiomycotina
      subdivision.

PMID- 9016954
TI  - Cloning, sequencing and expression of the two genes encoding the mitochondrial
      single-stranded DNA-binding protein in Xenopus laevis.
AB  - In Xenopus laevis the single-stranded DNA binding protein imported into the
      mitochondria consists of two highly related polypeptides. The establishment of
      the genomic nucleotide sequences reveals that they are encoded by two different
      genes, XLSSB1 and XLSSB2. The deduced amino acid sequence is identical to the
      direct amino acid sequence determined by Edman degradation of the mitochondrial
      polypeptides [Ghrir. R., Lecaer, J.P., Dufresne, C. and Gueride, M. (1991)
      Primary structure of the two variants of Xenopus laevis mtSSB, a mitochondrial
      DNA binding protein. Arch. Biochem. Biophys. 291, 395-400]. Both genes are
      organized in seven exons and six introns, the sequence of the peptide leader is
      interrupted by an intervening sequence (intron 2). The exon/intron junctions are
      in exactly conserved positions, splitting the same codon. A high level of
      identity is observed between corresponding introns of the two genes over part or
      most of their lengths. Structural features of intronic sequences reveal multiple
      rearrangements and exchanges during the evolution of X. laevis species. A CCAAT
      box and the potential regulatory elements NRF-2 and Sp 1 are observed in the 5'
      flanking region of both genes. During oogenesis, XLSSB gene expression is
      correlated with the replicative activity of the mitochondrial DNA.

PMID- 9016955
TI  - Fluorescent differential display analysis of gene expression in differentiating
      neuroblastoma cells.
AB  - Identification of differentially-expressed genes provides an important step
      toward the elucidation of molecular mechanisms underlying a variety of biological
      processes. A novel PCR-based approach to detect and clone such transcripts is the
      so-called differential display (DD). We established an improved DD protocol that
      can be performed on an automated fluorescent DNA sequencer to ensure high
      throughput as well as operational safety. Using this fluorescent DD (FDD)
      technique, we analyzed the gene expression profile in the retinoic acid-induced
      differentiation of a human neuroblastoma cell line SH-SY5Y. Screening with 102
      primer combinations at eight different time points revealed 66 cDNA bands with
      variously different behaviors out of approximately 6000 bands displayed.
      Subsequent analyses with 15 cloned species confirmed the differential expression
      of corresponding transcripts in all the cases, thereby demonstrating the high
      reliability of FDD analysis. These clones were composed of seven novel and eight
      known genes, the latter of which included those that had never been described in
      the context of neuronal differentiation. These results indicate that FDD is an
      effective approach to obtain not only novel genes but also clues to possible
      novel functions of known genes involved in various biological phenomena.

PMID- 9016956
TI  - Arabidopsis thaliana ECP63 encoding a LEA protein is located in chromosome 4.
AB  - DCECP63 is a carrot embryogenic cell protein. To perform its genetic analysis, we
      isolated an Arabidopsis thaliana (At) ECP63 cDNA. The cDNA encoded a polypeptide
      of 449 amino acids (aa). Its deduced aa sequence showed extensive similarity with
      DCECP63, DCDC8 and BPBP8 which are embryonic proteins isolated from carrot and
      birch, respectively. The aa sequence contained eight well-conserved tyrosine
      phosphorylation sites and 16 repeats of 11 aa. Southern analysis showed that the
      AtECP63 gene might belong to a small multigene family. The AtECP63 transcripts
      accumulated specifically in mature seeds, and exogenous abscisic acid (ABA)
      induced its expression in immature siliques, but not in vegetative tissues. These
      results suggested that the AtECP63 gene encoding a putative phosphotyrosine
      protein belonging to late embryogenesis abundant (LEA) protein in group 3 might
      be involved in maturation and desiccation tolerance of seeds. Restriction
      fragment length polymorphism (RFLP) and cleaved amplified polymorphic sequence
      (CAPS) mapping showed that AtECP63 gene was present in the South part of
      chromosome 4.

PMID- 9016957
TI  - High copy number integration into the ribosomal DNA of the yeast Phaffia
      rhodozyma.
AB  - This report describes a transformation system leading to stable high copy number
      integration into the ribosomal DNA (rDNA) of the astaxanthin-producing yeast
      Phaffia rhodozyma. A plasmid was constructed that contains the transposon Tn5
      encoded kanamycin resistance gene (KmR) fused in frame to the 5'-terminal portion
      of the Phaffia actin gene. This marker, driven by the Phaffia actin promoter,
      confers resistance to G418 (Geneticin). The plasmid also contains a rDNA portion
      that comprises the 18S rDNA and promotes high copy integration leading to stable
      Phaffia transformants that maintained the plasmid at high copy number after 15
      generations of non-selective growth. Phaffia, strain CBS 6938, was found to
      contain the rDNA units in clusters distributed over three chromosomes with a
      total copy number of 61. Phaffia transformants were shown to have over 50 copies
      of pGB-Ph9 integrated in tandem in chromosomes that contain rDNA loci. The
      chromosomal shifts that occur as a result of these integrations as shown by
      pulsed field electrophoresis strongly suggest that Phaffia is haploid.

PMID- 9016958
TI  - Cloning and analysis of an HMG gene from the lamprey Lampetra fluviatilis: gene
      duplication in vertebrate evolution.
AB  - Evolution has shaped the organisation of vertebrate genomes, including the human
      genome. To shed further light on genome history, we have cloned and analysed an
      HMG gene from lamprey, representing one of the earliest vertebrate lineages.
      Genes of the HMG1/2 family encode chromosomal proteins that bind DNA in a non
      sequence-specific manner, and have been implicated in a variety of cellular
      processes dependent on chromatin structure. They are characterised by two copies
      of a conserved motif, the HMG box, followed by an acidic C-terminal region. We
      report here the cloning of a cDNA clone from the river lamprey Lampetra
      fluviatilis containing a gene with two HMG boxes and an acidic tail; we designate
      this gene LfHMG1. Molecular phylogenetic analysis shows that LfHMG1 is descended
      from a gene ancestral to mammalian HMG1 and HMG2. This implies that there was a
      duplication event in the HMG1/2 gene family, that occurred after the divergence
      of the jawed and jawless fishes, 450 million years ago. This conclusion supports
      and refines the hypothesis that there was a period of extensive gene duplication
      early in vertebrate evolution. We also show that the HMG1/2 family originated
      before the protostomes and deuterostomes diverged, over 525 million years ago.

PMID- 9016959
TI  - The locus of enterocyte effacement pathogenicity island of enteropathogenic
      Escherichia coli encodes secretion functions and remnants of transposons at its
      extreme right end.
AB  - The locus of enterocyte effacement (LEE) is necessary for enteropathogenic
      Escherichia coli to cause characteristic attaching and effacing lesions in host
      cells. To determine whether sequences at the extreme right end of the LEE
      downstream of the espB gene are required for attaching and effacing, we
      constructed a mutant with an omega-interposon insertion immediately downstream of
      espB. This mutant is incapable of attaching and effacing, of secreting EspA and
      EspB and of inducing tyrosine phosphorylation of host cell proteins. These
      phenotypes are restored by a plasmid containing the extreme right end of the LEE.
      The nucleotide sequence of this region reveals a relatively low G+C content,
      remnants of transposons, and several open reading frames. The predicted products
      of these open reading frames include a potential chaperone, a potential component
      of the secretion apparatus, and a hypothetical peptide with proline rich repeats
      reminiscent of several eukaryotic proteins. These data indicate that the extreme
      right end of the LEE is required for attaching and effacing and reveal
      information relevant to the origin and function of the LEE.

PMID- 9016960
TI  - Construction and characterization of a one-plasmid system for the controlled
      expression of genes in mammalian cells by tetracycline.
AB  - The two-plasmid system of Gossen and Bujard [Gossen and Bujard (1992) Proc. Natl.
      Acad. Sci. USA 89, 5547-5551] to express mammalian genes in a tetracycline
      repressed fashion was combined into a single-plasmid system. Two variants of this
      single-plasmid system that differ in the multiple cloning site (MCS) region are
      described. These vectors were used to stably transfect raf kinase domain into the
      normal rat kidney epithelial cell line (NRKE) to obtain a conditionally
      transformed cell line. These vectors were also used to stably transfect wild-type
      and mutant human p53 into the human osteosarcoma cell line, SAOS-2. Tetracycline
      repressed gene expression in both cell lines; about 12-fold in NRKE and about 80
      fold in SAOS-2 cell line.

PMID- 9016961
TI  - A natural longer glycine-rich region in IKe filamentous phage confers no
      selective advantage.
AB  - Filamentous phage infect bacteria bearing pili. The phage protein involved in the
      recognition of pili and subsequent penetration of the phage into bacteria is the
      gene 3 protein (g3p). This is a multi-domain protein with glycine-rich regions
      separating some of the domains. Here we have found an insertion within the
      glycine-rich domain of the g3p of IKe, a filamentous phage which infects bacteria
      bearing N pili. Although this insertion considerably increases the length of the
      glycine-rich domain it has no selective advantage or disadvantage in infection or
      production of phage, and can therefore be considered a neutral mutation.

PMID- 9016962
TI  - Characterisation of two promoters for prion protein (PrP) gene expression in
      neuronal cells.
AB  - The neuronal membrane protein, PrP, has a key role in the development of the
      transmissible spongiform encephalopathies and the level of expression of the PrP
      gene has been shown to affect the disease profile. In order to define the
      sequences that are responsible for the normal expression of the PrP gene we have
      isolated and sequenced a 5' region of the murine PrP gene, which includes 1.2 kb
      upstream from exon 1, intron I and exon 2. Sequencing of this region from several
      strains of mice identified a polymorphism linked to Sinc, the gene controlling
      the incubation period of scrapie in mice. We used this gene fragment and
      deletions of it to examine promoter mediated expression of a cat (chloramphenicol
      acetyl transferase) reporter gene in neuroblastoma cells (N2a). Both promoter and
      suppressor elements were identified within this region. The two major areas of
      promoter activity were sequences adjacent to and 5' to exons 1 and 2. The 5'
      region of intron 1 was shown to contain elements that were capable of suppressing
      promoter activity. Transcription factor binding sites have been identified within
      these sequences.

PMID- 9016963
TI  - Characterization of csgA, a new member of the forespore-expressed sigmaG-regulon
      from Bacillus subtilis.
AB  - A new locus, csgA, has been identified in a search for developmental genes
      transcribed by E sigmaG in Bacillus subtilis. csgA has the potential to encode
      three small proteins, CsgAA, CsgAB and CsgAC. The latter two would be encoded by
      overlapping ORFs. csgA is expressed in the spore chamber of the differentiating
      cell and is under the control of sigmaG and the transcriptional regulatory
      protein SpoVT. Mutation of csgA did not affect spore formation but produced a
      subtle defect in the ability of the germinating spore to resume vegetative
      growth.

PMID- 9016964
TI  - Postocclusive reactive hyperemia estimating peripheral vascular resistance: a
      noninvasive method to predict outcome of infrainguinal vascular reconstructions?
AB  - OBJECTIVE: The peripheral vascular resistance is an important factor determining
      the outcome of infrainguinal revascularizations. When measured intraoperatively,
      it correlates to graft patency, but to select patients to surgery a preoperative,
      preferably noninvasive, method is necessary. The aim of the present study is to
      test if parameters recorded during postocclusive reactive hyperemia can be used
      for that purpose. EXPERIMENTAL DESIGN: This prospective study compares patients
      with occluded grafts within 30 days postoperatively to patients with patent
      grafts. SETTING: University Hospital. PATIENTS: Thirty patients with critical
      ischemia scheduled for infrainguinal bypass surgery. MEASURES: Correlations
      between intraoperatively measured peripheral resistance and preoperatively
      recorded parameters of postocclusive reactive hyperemia. The ability of the
      values to predict outcome. RESULTS: Peripheral resistance correlated
      significantly to two parameters during postocclusive reactive hyperemia recorded
      after thigh occlusion, flux reappearance time (r=0.47, p=0.01) and time to peak
      flux (r=0.41, p=0.03). Intraoperative peripheral resistance predicted graft
      occlusion at 30 days with a 90% accuracy, while parameters obtained during
      reactive hyperemia, only tended to predict adverse outcome. CONCLUSIONS: Several
      parameters during reactive hyperemia show weak correlation to intraoperatively
      measured peripheral resistance, but none was able to accurately predict graft
      failure. Further studies are needed to evaluate its capability for patient
      selection.

PMID- 9016965
TI  - Directly visualized cerebral circulation during retrograde cerebral perfusion.
AB  - BACKGROUND: Retrograde cerebral perfusion (RCP) was clinically introduced as a
      supportive technique to protect the brain during operations on the thoracic
      aorta. However, it remains unclear whether this procedure provides adequate blood
      supply for the brain. METHODS: We have observed the optic fundus of patients
      undergoing operation on the thoracic aorta to evaluate the cerebral circulation
      during RCP. There were 1 male and 3 female patients, ages ranged from 34 to 78
      years. RCP time ranged from 39 to 70 minutes, and blood flow via the superior
      vena cava cannula ranged from 200 to 400 ml/min. RESULTS: The arteries of the
      retina showed marked constrictions soon after the initiation of RCP. The veins
      showed almost normal diameter. The large arteries were reduced to thin threads,
      while the smaller arteries were invisible at 30 minutes after the initiation of
      retrograde cerebral perfusion. CONCLUSION: Ophthalmoscopic findings demonstrate
      the reduction of cerebral blood flow, especially in arteries, during RCP.
      Although RCP is a useful technique for cerebral protection, it could be mentioned
      that the blood supply to the brain by RCP is not enough to maintain good cerebral
      metabolism.

PMID- 9016967
TI  - Aortocaval fistula in ruptured inflammatory abdominal aortic aneurysm. A report
      of two cases and literature review.
AB  - Inflammatory abdominal aortic aneurysms (IAAA) occur infrequently in clinical
      practice. The reported incidence varies from 2.5-15% of all abdominal aortic
      aneurysms (AAA). Four percent of all AAA rupture into the vena cava. IAAA
      rupturing into the vena cava is exceedingly rare. To date, four such cases have
      been reported. IAAA are associated with a thick, rigid aortic wall which may be
      thin posteriorly and posterolaterally, where they are likely to rupture. A dense,
      fibrotic, desmoplastic reaction is found in the periaortic tissues often
      involving the duodenum, the inferior vena cava, the left renal vein, and ureters.
      IAAA may present with abdominal, back, or flank pain even in the absence of
      rupture. The diagnosis of IAAA can be made preoperatively by CT scan and at the
      time of laparotomy. Aortocaval fistula (ACF) can occur as a complication of AAA.
      The triad of low back pain, a palpable AAA, and a machinery murmur is diagnostic.
      ACF in association with IAAA is even more rare. It is amenable to surgical
      correction using a standard technique of fistula repair from within the aneurysm
      and prosthetic aortic graft replacement. Two cases of AAA with aortocaval fistula
      (ACF) are presented. In both, the diagnosis of ACF was made preoperatively.
      Repair of ACF was performed from within the aneurysm, with subsequent graft
      replacement. Despite complicated postoperative courses, both patients survived.

PMID- 9016966
TI  - A simple technique for the prevention of lower limb ischemia during femoral veno
      arterial cardiopulmonary support.
AB  - OBJECTIVE: We describe a simple technique to prevent the lower limb ischemia
      during femoral veno-arterial cardiopulmonary support (CPS). PATIENTS: Between
      July 1994 and September 1995, five patients underwent the insertion of femoral
      veno-arterial CPS with distal limb perfusion for the treatment of circulatory
      collapse after cardiac surgery. METHODS: After CPS is established, the
      ipsilateral superficial femoral artery (SFA) is punctured downward with a 14
      gauge Teflon catheter and connected to the side port of the membrane oxygenator.
      RESULTS: None of the patients were complicated by lower limb ischemia for up to
      77 hrs on CPS with distal limb perfusion. CONCLUSIONS: Active perfusion through a
      14-gauge Teflon catheter downstream to the ipsilateral SFA is effective in
      preventing lower limb ischemia during prolonged femoral veno-arterial CPS after
      cardiac surgery.

PMID- 9016968
TI  - Aortoduodenal fistula. Two case reports and a review of the literature.
AB  - Aortoduodenal fistulas (ADF) are relatively rare causes of fatal exsanguination.
      They occur predominantly in the third and fourth parts of the duodenum. Symptoms
      of ADF consist of flank or abdominal pain, hematemesis, melena, and an abdominal
      mass. We report two fatal cases of ADF, one of which includes the afferent loop
      of a Billroth II anastomosis, an event previously unrecognized, as well as a more
      conventional case of ADF, involving the third portion of the duodenum.

PMID- 9016969
TI  - Aberrant right subclavian artery. An original median cervical approach.
AB  - The case of a 28-year-old woman with dysphagia secondary to oesophageal
      compression by an anomalous right subclavian artery is reported. A new single
      surgical approach, not previously described, for the treatment of dysphagia
      lusoria in the adults is presented. The aberrant vessel is dissected, divided
      close to its origin and implanted into the ipsilateral common carotid artery, all
      through a single median cervical incision.

PMID- 9016970
TI  - Temporary axillo-femoral bypass graft for renal transplant protection during
      aortic aneurysm repair.
AB  - Aortic surgery in renal transplant recipients requires a method of maintaining
      intraoperative graft perfusion. Here we present a case in which temporary axillo
      femoral bypass was used to perfuse a renal transplant during the aortic aneurysm
      repair; the rationale of inserting the temporary axillo-femoral bypass on
      transverse arteriotomies is pointed out. Other methods of renal graft perfusion
      are discussed.

PMID- 9016971
TI  - Inferior pancreaticoduodenal artery aneurysm associated with common hepatic
      artery occlusion.
AB  - A unique case of true inferior pancreaticoduodenal artery aneurysm (IPDA)
      associated with occlusion of common hepatic artery is reported. Radiological and
      MRI findings are described. Because of high risk of visceral ischemia that
      contraindicated a percutaneous transluminal embolization, a successful tangential
      resection of aneurysm was performed.

PMID- 9016972
TI  - Membranous obstruction of the inferior vena cava and Budd-Chiari syndrome. Report
      of a case.
AB  - Membranous obstruction of the inferior vena cava (MOIVC) is a rare, congenital or
      acquired, cause of Budd-Chiari syndrome leading to hepatocellular carcinoma in 20
      to 40% of the patients. It has a very poor prognosis when treated medically and
      balloon angioplasty (PTA) represents, nowadays, the treatment of choice, having
      no mortality or significant morbidity with follow-up as long as 5 years;
      transatrial membranotomy, direct reconstruction of IVC and bypass surgery are
      alternative techniques when PTA is not feasible. One case of Budd-Chiari syndrome
      due to an incomplete membranous obstruction of the suprahepatic portion of the
      inferior vena cava is reported. A PTA was not feasible as it was not possible to
      pierce the membranous obstruction. A successful inferior vena cava-right atrium
      PTFE bypass, with a 3.5-year follow-up, was performed. This surgical approach is
      a valuable alternative to transatrial membranotomy and direct reconstruction of
      the IVC.

PMID- 9016973
TI  - Infectious aneurysm of the interosseous artery at the forearm. Case report.
AB  - The case of an infectious aneurysm of the interosseous artery at the right
      forearm is reported, with presenting symptoms consisting in pain, loss of motor
      functions and paresthesias. The association of occupational trauma and
      hematogenous bacterial grafting were the possible etiologic agents. Diagnostic
      evaluation included ultrasound, Doppler study, CT-scan and arteriography, but the
      exact origin of the mass from the interosseous artery could be detected only at
      operation. As good collaterals were present at preoperative evaluation, simple
      excision followed by debridment and ligation was performed with a good result.
      The isolated infecting agent belonged to the salmonella species.

PMID- 9016974
TI  - Treatment of haemorrhage following rupture of aortic leiomyosarcoma. Survival for
      4.2 years.
AB  - This paper describes a case of hemorrhage from an aortic leiomyosarcoma in which
      the patient exceptionally survived for 4.2 years after surgery. The operation
      consisted of resection of the aortic tract involved by the tumour and graft of a
      prosthesis. The diagnosis of aortic leiomyosarcoma had been based on the
      histological analysis and confirmed by histochemical and immunohistochemical
      findings.

PMID- 9016975
TI  - The Carbomedics prosthetic heart valve: four year follow-up in 100 patients.
AB  - From December 1988 to December 1991, 100 patients underwent valve replacement
      with a Carbomedics bileaflet valve in our institution (55 aortic valve
      replacements, 28 mitral valve replacements, and 17 double valve replacements).
      Fifty-nine percent were males. Mean age was 55.7+/-12.3 years. Fifty eight
      percent of patients were in NYHA Clinical status III or IV. Operative mortality
      was 3% (3/100). All patients but one were followed up for an average of 2.8 years
      after their operation and total follow-up was 280 patient years. At the time of
      the study, more than 80% of patients were in NYHA class I or II, 34% were in
      atrial fibrillation and 100% of patients received anticoagulation treatment.
      There were 3 late deaths. After 4 years, the actuarial survival rate was 94%+/
      5%. No patients died of valve-related causes. Valve-related complications
      included 2 thromboembolic episodes (0.7%-patient-year), 8 anticoagulant-related
      complications (2% patient-year), and one reoperation (0.3% patient-year). After 4
      years, freedom from thromboembolic complication was 96%+/-4%, from endocarditis
      was 100%, from reoperation was 99%+/-1%, and from anticoagulant-related
      complications was 93%+/-5%. We conclude that the 4-year results compare with
      other bileaflet valves. More follow-up and larger studies are mandated to give
      definite conclusions.

PMID- 9016976
TI  - The use of pulmonary allografts for aortic valve replacement. Short term results
      and comparative morphometric analysis of the aortic and pulmonary valves.
AB  - The satisfactory results of aortic valve replacement with pulmonary autograft and
      the limited availability of aortic allografts prompted us to use the pulmonary
      valve as an aortic valve substitute and to perform a morphometric analysis of the
      two valves in cadavers. CLINICAL STUDY: From March 1994 to March 1995 20 patients
      underwent an aortic valve replacement (AVR) with a pulmonary allograft (PA).
      Twelve patients were men, 8 women; age ranged from 15 to 58 years. In 4 cases the
      indication to AVR was an infective endocarditis which was acute in two patients.
      Functional class was NYHA II in 18 cases and NYHA III in 2 patients with active
      endocarditis. Left ventricular ejection fraction (LVEF%) was preserved in the
      majority of patients (mean LVEF=53% range 36% to 65%). End diastolic aortic valve
      diameters were measured by bidimensional echocardiography in parasternal long
      axis view and ranged from 18 mm to 29 mm. The diameters of the allografts
      implanted ranged from 19 mm to 27 mm. Donors age ranged from 19 years to 55
      years. We tried to use the allograft from the youngest donor available. The
      surgical technique was the classic "Ross" coronary freehand implantation in 11
      cases, a "Miniroot" implant in 8 instances and a "Miniroot" implant combined with
      a "Nicks" annular enlargment in 1 case. Aortic cross clamping ranged from 66 mm
      to 118 m (92m+/-10m). One patient died (5%) of infarction. In this patient the
      allograft was replaced with a mechanical valve because the echocardiography
      showed a rapidly increasing aortic regurgitation. At hospital discharge a slight
      aortic regurgitation was detected in 2 cases. In these two patients, whose
      annulus diameters were 26 mm and 28 mm respectively, we adopted a classic
      freehand technique of implantation. Mean postoperative transvalvular gradient was
      4 mmHg+/-3 mmHg. The follow-up ranges from 45 days to 14 months (mean 8 months).
      The aortic regurgitation in the two cases remains stable and no new aortic
      regurgitations have been detected to date. No embolic or infective episodes
      occurred during the follow-up. ANATOMIC STUDY: Analysis was performed on 6
      couples of valves obtained from cadevers without evidence of previous valvular
      disease. The normalized Free Edge (FE) dimensions and Leaflet Surfaces (LS) of
      the pulmonary valve (PV) proved to be larger than the corresponding aortic (AV)
      measurements (Free edge/Diameter: PV 1.25+/-0.2 vs AV 1.16+/-0.2 p<0.05; Annular
      Attachment/Diameter PV 1.9+/-0.1 vs AV 1.74+/-0.2 p=NS; Valve Surface/Leaflet
      Surface PV 0.97+/-0.2 vs AV 0.80+/-0.2 p=0.004) indicating that the PV has a
      larger coapting surface.

PMID- 9016977
TI  - 99mTc-sestamibi and 201-Thallium at rest: dual scintigraphic mapping of
      myocardial injury in infarcted patients.
AB  - 201-Thallium (Tl) and (99m)Tc-sestamibi (SM) present different biological
      properties and kinetics, suggesting a complementary evaluation of mitochondrial
      and cell membrane functions with subsequent implications regarding myocardial
      injury mapping. To verify the usefulness of a dual isotopic approach in Q
      infarcted patients, 30 subjects were submitted at rest, within 5 days, to SM
      imaging, 4h-delayed Tl scans and echocardiography (ECHO). Left ventricle
      segmental uptake and wall motion were graded on a 3 points scale (0=absent to
      2=normal) and compared on the basis of an 11 segments model. RESULTS AND
      DISCUSSION: 1) The analysis of SM normal segments demonstrated a strong
      concordance (97%) with Tl and ECHO, suggesting that both mitochondrial and cell
      membrane functions are preserved; 2) 49% of SM graded 0 segments were scored 1 by
      Tl and ECHO, suggesting a worse impairment of mitochondrial function with respect
      to cell membrane function; 3) approximately 55% of segments showing a reduced
      MIBI uptake were found normal using Tl, then an impaired mitochondrial but a
      normal cell membrane function could be hypothesized. 4) Tl provided a better
      estimation of the effective infarction size with respect to SM. CONCLUSIONS: The
      SM and Tl dual approach, allowing scintigraphic mapping of myocardial injury,
      seems to provide a useful tool for a complete evaluation of infarcted patients.

PMID- 9016978
TI  - Late posterior cardiac tamponade after open heart surgery.
AB  - OBJECTIVE: Late cardiac tamponade after open heart surgery is a relatively
      uncommon, but potentially serious complication. We retrospectively analyzed 14
      patients who had posterior cardiac tamponade 13 to 210 days after open heart
      surgery. PATIENTS: Between May 1988 and July 1995, 3150 adult patients underwent
      open heart surgery at the Gulhane Military Medical Academy. In 35 of 3150
      patients (1.11%) late pericardial effusions developed, and in 14 (0.44% of 3150
      consecutive open heart surgery performed on adult patients in our center) of
      these patients had posterior tamponade. There were moderate symptoms including
      fatigue, malaise, and dyspnea on exertion in all patients. The diagnosis was made
      by echocardiography in 13 patients, and by tomographic scanning in 1 patient.
      Analysis of these 14 patients revealed that all of them had hemodynamic criteria
      consistent with tamponade physiology on right heart catheterization with Swan
      Ganz catheters. RESULTS: Echocardiography guid pericardiocentesis through the
      left anterior axillary line was effective in decompressing of posterior cardiac
      tamponade in 10 of 14 patients. Three patients required operative surgical
      drainage after unsuccessful pericardiocentesis through subxiphoid area. Two
      patients who underwent surgical drainage died, and in one patient surgical
      pericardiotomy had complete evacuation of posterior pericardial fluid with major
      complication. CONCLUSIONS: 2-D echocardiography guid pericardiocentesis through
      left anterior axillary line was found to be a useful, safe, and simple technique.
      It can be used as an alternative treatment to surgical pericardiotomy for
      posterior cardiac tamponade after open heart surgery.

PMID- 9016980
TI  - Cardiopulmonary bypass procedures in patients with cold-reactive
      hemagglutination. A case report and a literature review.
AB  - The use of hypothermia during cardiopulmonary bypass and cardioplegia poses a
      special problem in patients with cold-reactive hemagglutination. This is a case
      report of a successful aortic valve replacement on a patient with severe aortic
      valve stenosis and severely symptomatic cold agglutinin induced hemolytic anemia.
      This case illustrates the various problems in the perioperative management of
      these patients. A literature review of these rare cases is provided.

PMID- 9016979
TI  - Osteogenesis imperfecta and coronary artery surgery. A case report.
AB  - A new case of Osteogenesis Imperfecta (OI) suffering ischemic heart disease is
      reported. The patient was successfully operated on in our Institution and the
      bibliographic search showed only another case of such an association of diseases
      successfully treated by surgery. This patient proves that coronary artery surgery
      procedures are possible when OI complicates the cardiac ischemic syndrome.

PMID- 9016981
TI  - Subacute left ventricular free wall rupture complicating acute myocardial
      infarction. Successful surgical repair with a sutureless technique.
AB  - The high mortality index related to surgical therapy with direct suture of
      rupture of left ventricular free wall following acute myocardial infarction,
      suggested we analyze and use alternative techniques. So we applied sutureless
      technique described by Padro to two patients. We used a Teflon patch fixed to the
      ventricular wall with a biocompatible synthetic glue, an ethyl-2-cyanoacrylate
      monomer, without any direct suturing of the infarcted myocardium. The two
      patients survived the operation and were discharged from the hospital 12 and 14
      days after surgery. The sutureless technique allows, in our opinion, a more
      confident and safe aggressive attitude to subacute left ventricular free wall
      rupture.

PMID- 9016982
TI  - Prosthetic valve endocarditis due to Legionella pneumophila.
AB  - Prosthetic valve endocarditis is a potential complication of valve replacement
      surgery and warrants prompt diagnosis and appropriate treatment. Thus, the blood
      culture in addition to providing an etiological organism is important in
      establishing appropriate antibiotic therapy. A case of prosthetic valve
      endocarditis (PVE) is presented with repeatedly negative blood cultures at a
      community hospital and refractory to prolonged therapy with standard antibiotic
      regimens. Appropriate workup eventually identified the causative organism as
      Legionella pneumophila, and antimicrobial therapy directed against Legionella
      combined with a repeat valve replacement effectively treated this case. Aspects
      of culture-negative PVE including the microbiology and etiology are discussed.
      Legionella endocarditis represents an important cause of culture negative PVE and
      should be considered in the differential diagnosis of culture negative PVE
      refractory to standard antimicrobial therapy.

PMID- 9016983
TI  - Pseudoaneurysm of the left ventricle following repair for ventricular septal
      perforation.
AB  - The patient was a 64-year-old man who was treated surgically for an infarct
      related ventricular septal perforation. Pseudoaneurysm of the left ventricle was
      recognized on the 38th postoperative day. Emergency surgery was performed. It
      seemed that insufficient resection of the infarcted myocardium was performed
      during the initial surgery to avoid narrowing the ventricular dimension by direct
      closure of the left ventricle, but this resulted in pseudoaneurysm of the left
      ventricle. Left ventricular free wall plasty with a patch should be performed
      during the initial surgery.

PMID- 9016984
TI  - Echocardiography and magnetic resonance imaging of sinus of Valsalva aneurysm
      with rupture into the ventricle.
AB  - A 53 year-old man with rupture of sinus of Valsalva aneurysm into the right
      ventricle diagnosed by two dimensional echocardiography (2DE), magnetic resonance
      imaging (MRI), and catheterisation study is reported in this paper. Despite the
      fact that its incidence is low, early diagnosis is very important in this illness
      because of the possibility of complete cure with surgery. In this study it was
      shown that MRI as well as 2DE is an excellent diagnostic method for this illness.
      The diagnosis was also confirmed with surgery in this patient.

PMID- 9016985
TI  - Endovascular stenting of an aortopulmonary fistula presenting with hemoptysis. A
      case report.
AB  - We present a 45 year old man with massive hemoptysis due to an aortopulmonary
      fistula. Our patient had a history of a previous patent ductus arteriosus repair
      which was complicated by a previous aortopulmonary fistula. Computed tomography
      of the chest and aortography made the diagnosis of a recurrent aortopulmonary
      fistula. Because of the history of previous surgical aortic procedures, repair of
      the fistula was completed through a retroperitoneal aortotomy with intravascular
      insertion of an expandable stainless steel stent covered by a polyester graft.
      The patient has had no hemoptysis or computed tomographic evidence of fistula
      recurrence thirty eight months after the procedure.

PMID- 9016986
TI  - Type II cystic adenomatoid malformation: late diagnosis in a patient with a
      pulmonary mass.
AB  - We hereby report the case of a 22-year-old patient with a final diagnosis of type
      II cystic adenomatoid malformation, who was hospitalized due to repeated
      pulmonary infections. The radiographic study demonstrated a worrying image of a
      pulmonary mass. The different studies performed, did not put forward the
      diagnosis, so at last the patient was proposed a thoracotomy for diagnostic and
      therapeutic purposes.

PMID- 9016987
TI  - Carcinoma arising within epiphrenic diverticula. A report of two cases and review
      of the literature.
AB  - Two patients with squamous cell carcinoma arising within an epiphrenic
      diverticulum are reported bringing the total reported in the English-language
      literature to fifteen. The majority of patients with carcinoma arising in an
      epiphrenic diverticulum are elderly males who have been symptomatic for years
      with a known diverticulum. This is the first report of multiple cases of
      carcinoma within an epiphrenic diverticulum from a single institution and the
      first report in a female patient. Similar to other reports, these two patients
      presented with several months of symptoms related to their esophageal
      diverticulum. It is important to entertain the diagnosis of esophageal carcinoma
      early in the evaluation of patients with signs and symptoms suggestive of
      epiphrenic diverticula as early intervention may be the only chance of cure.

PMID- 9016988
TI  - Neuroendocrine carcinomas of the lung and role of 111In-DTPA-octreotide
      scintigraphy: preliminary results.
AB  - The authors report their experience on the use of 111In-DTPA-octreotide
      scintigraphy in the diagnosis of neuroendocrine carcinomas of the lung. The
      studies were performed both preoperatively, to obtain a correct staging of the
      tumor, or postoperatively, because of the suspicion of a recurrence or distant
      metastases. The main findings were: high sensitivity in localizing the tumor and
      its recurrences or metastases and high predictive value for responsiveness to
      "cold" octreotide therapy.

PMID- 9016994
TI  - Toward therapeutic intervention of cancer by vitamin D compounds.

PMID- 9016995
TI  - Analysis of cytokine profiles in patients with human papillomavirus-associated
      neoplasms.

PMID- 9016996
TI  - Why do African-American men suffer more prostate cancer?

PMID- 9016998
TI  - Major cancer groups form "Friends of Cancer Research".

PMID- 9016997
TI  - Cord blood's role in cancer therapy awaits answers.

PMID- 9016999
TI  - Impotence is not inevitable after prostate cancer treatment.

PMID- 9017000
TI  - Molecular epidemiology and retinoid chemoprevention of head and neck cancer.
AB  - Head and neck cancer is a major worldwide health problem; it has been estimated
      that approximately 900,000 people were diagnosed with this disease in 1995.
      Patients are generally treated with surgery and/or radiation therapy. Treatment,
      especially of patients with early stage (I or II) head and neck squamous cell
      carcinoma, is often successful. A serious concern, however, is the fact that
      these patients subsequently develop second primary tumors at an annual rate of 4%
      7%. Molecular analyses of premalignant and malignant tissues have produced strong
      evidence that clonal genetic alterations occur during the early stage of
      aerodigestive tract carcinogenesis. Although the roles of tobacco and diet in
      head and neck carcinogenesis have been the subjects of epidemiologic
      investigations for many years, it has only recently become possible to integrate
      information regarding genetic susceptibility factors into the development of
      comprehensive risk models for these cancers. The molecular and epidemiologic
      studies provide the foundation on which clinical trials can be designed to
      evaluate the role of retinoids and other compounds in the reversal of
      premalignancy and the prevention of second primary tumors (i.e., in
      chemoprevention). This translational approach has led to studies of the utility
      of intermediate end point markers, such as the nuclear retinoic acid receptors,
      in chemoprevention strategies. Given the rapid advances occurring in this area of
      research, it may soon be possible to use these biomarkers to identify patients
      who are most at risk for developing head and neck cancer and who are most likely
      to benefit from chemopreventive interventions.

PMID- 9017001
TI  - Prevention of preneoplastic mammary lesion development by a novel vitamin D
      analogue, 1alpha-hydroxyvitamin D5.
AB  - BACKGROUND: The form of vitamin D (vitamin D3) in fortified milk and the
      provitamin D produced by the body undergo metabolic activation to a biologically
      active form, 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. This compound can
      induce cell differentiation and can prevent proliferation of cancer cells.
      However, because 1alpha,25(OH)2D3 is hypercalcemic (effective in increasing serum
      calcium level), it is not suitable for use in cancer prevention or cancer therapy
      trials. PURPOSE: We synthesized a vitamin D5 series analogue, 1alpha-hydroxy, 24
      ethyl-cholecalciferol, or 1alpha-hydroxyvitamin D5 [1alpha(OH)D5], and evaluated
      its chemopreventive activity in carcinogen-treated mammary glands in organ
      culture experiments. METHODS: The analogue 1alpha(OH)D5 was synthesized from
      sitosterol acetate and was characterized by nuclear magnetic resonance. Its
      purity was evaluated by high-pressure liquid chromatography. The calcemic
      activities of vitamin D3 and D5 analogues were determined in vitamin D-deficient
      Sprague-Dawley rats. Mammary glands of BALB/c mice were placed in organ culture
      and treated with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) to induce
      preneoplastic lesions. Vitamin D analogues were added to the culture medium at
      four different concentrations, and formation of mammary lesions was evaluated.
      The effects of 1alpha(OH)D5 and 1alpha,25(OH)2D3 on the expression of vitamin D
      receptors (VDRs) and transforming growth factor-beta1 (TGF-beta1) were studied by
      immunohistochemistry. Statistical significance was determined by the chi-squared
      test. All reported P values were two-sided. RESULTS: 1alpha,25(OH)2D3 was
      fourfold more calcemic than 1alpha(OH)D5 at a dose of 0.042 microg/kg per day in
      rats. Both 1alpha,25(OH)2D3 and 1alpha(OH)D5 inhibited the development of DMBA
      induced preneoplastic lesions in mouse mammary glands compared with untreated
      glands. The effect of the vitamin D3 analogue was observed at a much lower
      concentration (0.01 microM). Treatment with 1alpha(OH)D5 resulted in a dose
      related (0.01-10.0 microM) inhibition without any toxicity, whereas the vitamin
      D3 analogue was highly potent but toxic at concentrations of 1.0 microM or
      higher. Normal mouse mammary glands poorly express VDR and TGF-beta1; incubation
      with 1alpha(OH)D5 or 1alpha,25(OH)2D3 dramatically induced their expression.
      CONCLUSIONS: This is the first report showing the possibility of chemoprevention
      by a vitamin D5 series compound. We conclude that 1alpha(OH)D5 is less calcemic
      than 1alpha,25(OH)2D3. It is nontoxic at a wide range of concentrations, but it
      is potent in inhibiting the development of preneoplastic lesions in mammary
      glands in organ culture. In addition, we show for the first time the induction of
      TGF-beta1 in normal mammary tissues by a chemopreventive agent. IMPLICATIONS:
      1alpha(OH)D5 is a good candidate for in vivo chemoprevention studies. It may
      mediate its action by inducing expression of VDR and of TGF-beta1, as is seen in
      other systems.

PMID- 9017002
TI  - Thrombospondin-1 expression in bladder cancer: association with p53 alterations,
      tumor angiogenesis, and tumor progression.
AB  - BACKGROUND: Thrombospondin-1 (TSP) is a 430-kd glycoprotein that is an important
      component of the extracellular matrix and is known to be a potent inhibitor of
      angiogenesis (i.e., formation of new blood vessels) both in vitro and in vivo.
      Several reports suggest that TSP possesses tumor suppressor function, possibly
      through its ability to inhibit tumor neovascularization. It has recently been
      shown that TSP expression is enhanced by the product of the p53 gene (also known
      as TP53). PURPOSE: We examined the role of TSP expression in tumor recurrence and
      overall survival in patients with invasive bladder cancer. We also examined the
      relationship between alterations in p53 protein expression, TSP expression, and
      tumor angiogenesis. METHODS: Tumors from 163 patients (with a median follow-up of
      7.7 years) who underwent radical cystectomy for invasive transitional cell
      carcinoma of the bladder (63 patients with organ-confined disease and no lymph
      node involvement, 48 patients with extravesical extension of the disease and no
      lymph node involvement, and 52 patients with metastasis to regional lymph nodes)
      were examined for TSP expression by immunohistochemistry, utilizing monoclonal
      antibody MA-II, which recognizes an epitope in the amino-terminal region of TSP.
      For each tumor, microvessel density counts and p53 protein expression status (via
      immunohistochemistry) were also determined. TSP expression was graded as low,
      moderate, or high without knowledge of clinical outcome, p53 status, and
      microvessel density count; tumors with moderate and high TSP levels were
      considered as one group. Groups of patients were compared by Kaplan-Meier product
      limit estimates of overall survival, the complement of cumulative incidence
      curves for recurrence-free survival, and the stratified logrank test. Reported P
      values are two-sided. RESULTS: TSP expression was significantly associated with
      disease recurrence (P = .009) and overall survival (P = .023). Patients with low
      TSP expression exhibited increased recurrence rates and decreased overall
      survival. TSP expression was an independent predictor of disease recurrence (P =
      .002) and overall survival (P = .01) after stratifying for tumor stage, lymph
      node status, and histologic grade, but it was not independent of p53 status. TSP
      expression was significantly associated with p53 expression status (P = .001) and
      microvessel density counts (P = .001). Tumors with p53 alterations were
      significantly more likely to demonstrate low TSP expression, and tumors with low
      TSP expression were significantly more likely to demonstrate high microvessel
      density counts. Results of an analysis of variance were compatible with the
      hypothesis that p53 affects tumor angiogenesis by regulating the level of TSP
      expression. CONCLUSIONS AND IMPLICATIONS: These data support the concept that TSP
      may possess a tumor-inhibitory function. TSP may act, in part, through the
      regulation of tumor neovascularity. These results may also provide insight into
      one mechanism by which p53 exerts its tumor suppressor effects, i.e., through the
      control of tumor angiogenesis.

PMID- 9017003
TI  - Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on
      family history.
AB  - BACKGROUND: Heritable mutations of the breast cancer gene BRCA1 are rare,
      occurring in fewer than 1% of women in the general population, and therefore
      account for a small proportion of cases of breast and ovarian cancers.
      Nevertheless, the presence of such mutations is highly predictive of the
      development of these cancers. PURPOSE: We developed and applied a mathematic
      model for calculating the probability that a woman with a family history of
      breast and/or ovarian cancer carries a mutation of BRCA1. METHODS AND RESULTS: As
      a basis for the model, we use Mendelian genetics and apply Bayes' theorem to
      information on the family history of these diseases. Of importance are the exact
      relationships of all family members, including both affected and unaffected
      members, and ages at diagnosis of the affected members and current ages of the
      unaffected members. We used available estimates of BRCA1 mutation frequencies in
      the general population and age-specific incidence rates of breast and ovarian
      cancers in carriers and noncarriers of mutations to estimate the probability that
      a particular member of the family carries a mutation. This probability is based
      on cancer statuses of all first- and second-degree relatives. We first describe
      the model by considering single individuals: a woman diagnosed with breast and/or
      ovarian cancer and also a woman free of cancer. We next considered two artificial
      and two actual family histories and addressed the sensitivity of our calculations
      to various assumptions. Particular relationships of family members with and
      without cancer can have a substantial impact on the probability of carrying a
      susceptibility gene. Ages at diagnosis of affected family members and their types
      of cancer are also important. A woman with two primary cancers can have a
      probability of carrying a mutation in excess of 80%, even with no other
      information about family history. The number and relationships of unaffected
      members, along with their current ages or ages at death, are critical
      determinants of one's carrier probability. An affected woman with several cancers
      in her family can have a probability of carrying a mutation that ranges from
      close to 100% to less than 5%. CONCLUSION: Our model gives informative and
      specific probabilities that a particular woman carries a mutation. IMPLICATIONS:
      This model focuses on mutations in BRCA1 and assumes that all other breast cancer
      is sporadic. With the cloning of BRCA2, we now know that this assumption is
      incorrect. We have adjusted the model to include BRCA2, but the use of this
      version must await publication of penetrance data for BRCA2, including those for
      male breast cancer that are apparently associated with BRCA2 but not with BRCA1.
      The current model is, nevertheless, appropriate and useful. Of principal
      importance is its potential and that of improved versions for aiding women and
      their health care providers in assessing the need for genetic testing.

PMID- 9017004
TI  - Paternal cigarette smoking and the risk of childhood cancer among offspring of
      nonsmoking mothers.
AB  - BACKGROUND: Cigarette smoking has been shown to increase oxidative DNA damage in
      human sperm cells. Assessment of the role of cigarette smoking in the etiology of
      childhood cancer has focused primarily on the effect of maternal smoking. Similar
      studies in relation to paternal smoking, however, have been inconclusive. Few
      studies have evaluated the effect of paternal smoking in the preconception
      period, and most of these could not disentangle the effects of paternal from
      maternal smoking. PURPOSE: We investigated the relationship of paternal smoking,
      particularly in the preconception period, with childhood cancer among offspring
      of the nonsmoking mothers. METHODS: We conducted a population-based, case-control
      study in Shanghai, People's Republic of China, where the prevalence of smoking is
      high among men but extremely low among women. The study included 642 childhood
      cancer case patients (<15 years of age) and their individually matched control
      subjects. Information concerning parental smoking, alcohol drinking, and other
      exposures of the index child was obtained by direct interview of both parents of
      the study subjects. Odds ratios (ORs), derived from conditional logistic
      regression models, were used to measure the association between paternal smoking
      and risk of childhood cancers. RESULTS AND CONCLUSIONS: Paternal preconception
      smoking was related to a significantly elevated risk of childhood cancers,
      particularly acute leukemia and lymphoma. The risks rose with increasing pack
      years of paternal preconception smoking for acute lymphocytic leukemia (ALL) (P
      for trend = .01), lymphoma (P for trend = .07), and total cancer (P for trend =
      .006). Compared with children whose fathers had never smoked cigarettes, children
      whose fathers smoked more than five pack-years prior to their conception had
      adjusted ORs of 3.8 (95% confidence interval [CI] = 1.3-12.3) for ALL, 4.5 (95%
      CI = 1.2-16.8) for lymphoma, 2.7 (95% CI = 0.8-9.9) for brain tumors, and 1.7
      (95% CI = 1.2-2.5) for all cancers combined. Statistically significant increased
      risks of cancer were restricted to children under the age of 5 years at diagnosis
      or those whose fathers had smoked during all of the 5 years prior to conception.
      IMPLICATIONS: Further studies are needed to confirm the association of paternal
      smoking with increased risk of cancer in offspring, to clarify the pattern of
      risks in relation to the timing of cigarette smoking, and to elucidate the
      biologic mechanism involved in predisposing the offspring to cancer. For example,
      it may be that paternal smoking induces prezygotic genetic damage that, in turn,
      acts as the predisposing factor.

PMID- 9017005
TI  - Cytokine production patterns in cervical intraepithelial neoplasia: association
      with human papillomavirus infection.
AB  - BACKGROUND: Genital infection with certain strains of human papillomavirus (HPV)
      is associated with a high risk of malignant transformation, and HPV-associated
      cervical intraepithelial neoplasia (CIN) can become invasive cancer. Host factors
      are critical in regulating tumor growth, and cytokines that modulate immunologic
      control may be of particular importance. The type 1 cytokines interleukin 2 (IL
      2) and interferon gamma (IFN gamma) are immunostimulatory and are thus capable of
      limiting tumor growth. The type 2 cytokines interleukin 4 (IL-4) and interleukin
      10 (IL-10) are immunoinhibitory and are thus capable of stimulating tumor growth.
      PURPOSE: We analyzed the production of cytokines by peripheral blood mononuclear
      cells (PBMCs) in women with CIN associated with localized or extensively spread
      HPV infection. METHODS: Thirty women diagnosed with CIN and 10 age- and sex
      matched healthy control subjects were enrolled in the study conducted at Istituto
      Nazionale Tumori, Milan, Italy. The following parameters were analyzed: 1) HPV
      infection of the cervix and other sites of the lower genital tract by
      colposcopic, cytologic, and histologic examinations; 2) HPV typing; 3) in vitro
      production of IL-2 by PBMCs in response to stimulation with soluble antigen
      (influenza [FLU] antigen) or to cell-associated human leukocyte antigen (HLA)
      alloantigen; and 4) in vitro production of the type 1 cytokines IL-2 and IFN
      gamma and of the type 2 cytokines IL-4 and IL-10 by PBMCs in response to mitogen
      stimulation. Statistical significance was determined by nonparametric tests (two
      sided). RESULTS: High-grade CIN associated with HPV infection was detected in all
      case patients, and HPV type 16 or 18 infection was detected in cervical tissue of
      21 (70%) of 30 case patients. HPV infection that had spread to other sites of the
      lower genital tract, thus resulting in more extensive disease, was detected in 16
      (53%) of the 30 individuals with CIN, whereas HPV infection was limited to the
      portio in 14 (47%). IL-2 production by PBMCs in response to stimulation with
      soluble antigen or HLA alloantigen was reduced in the group with extensive
      disease compared with that in the group with localized disease or with that in
      healthy control subjects. In contrast, IL-4 and IL-10 production in response to
      mitogen stimulation was elevated in the group with extensive disease compared
      with that in the group with localized disease or with that in healthy control
      subjects. The highest production of IL-4 and IL-10 was detected in patients with
      HPV infection that had extended beyond the genital tract. CONCLUSIONS: CIN is
      characterized by different immunologic profiles, in which HPV infection is or is
      not confined to the portio. Production of cytokines that mainly enhance
      potentially protective cell-mediated immunity is defective in the women in whom
      extended HPV infection was observed. A pronounced shift from type 1 to type 2
      cytokine production is associated with more extensive HPV infection.
      IMPLICATIONS: These data reinforce the need for detailed analyses of immune
      dysregulation in CIN patients. They also suggest the potential usefulness of the
      cytokine assays for determining prognosis or deciding whether cytokine-based
      therapy is indicated.

PMID- 9017007
TI  - Low-dose isotretinoin versus beta-carotene to prevent oral carcinogenesis: long
      term follow-up.

PMID- 9017006
TI  - Birth cohort and calendar period trends in breast cancer mortality in the United
      States and Canada.
AB  - BACKGROUND: Previous studies of regional and temporal variation in U.S. breast
      cancer mortality rates have been confined largely to analyses of rates for white
      women. PURPOSE: Breast cancer mortality rates from 1969 through 1992 for white
      women and black women in four regions of the United States and for all women
      throughout Canada were compared to identify racial, regional, and temporal
      differences. Differences and trends in the rates were evaluated in view of breast
      cancer risk factors and relevant medical interventions. METHODS: Age-period
      cohort models were fit to the data, and changes in birth cohort trends
      (suggesting a change in a breast cancer risk factor or protective factor) and
      calendar period trends (suggesting, in part, the impact of new or improved
      medical interventions) were examined. RESULTS: Breast cancer mortality rates for
      white women were significantly higher in the Northeast than in any other region
      of the United States (two-sided t tests; P<.005); the rates for black women were
      not. Birth cohort trends for all women were similar until about 1940, with a
      moderation of mortality risk beginning around 1924. A marked moderation of risk
      by 4-year birth cohorts was observed for U.S. white women born after 1950,
      whereas stable or slightly decreasing trends were observed for U.S. black women
      and Canadian women. For women born from 1924 to around 1938, fertility rates
      increased for all three groups; after 1950, they declined uniformly. Looking at
      temporal effects, we found that the slope of the mortality calendar period trend
      increased in the 1980s compared with the 1970s for all women. In the last
      calendar period, 1991-1992, a trend of decreasing mortality rates was found for
      white women in the United States and for Canadian women. IMPLICATIONS: Widespread
      environmental exposures are unlikely to explain the higher relative breast cancer
      mortality rates observed for U.S. white women in the Northeast, since the rates
      for black women in this region were not higher than in other regions. The
      moderation of breast cancer mortality rates for women born between 1924 and 1938
      coincides with increased fertility rates following World War II. Stable or
      decreasing mortality rates for U.S. women and Canadian women born after 1950 were
      not expected in view of declining fertility rates, suggesting a change in a
      breast cancer risk factor or protective factor. The increase in calendar period
      trend slope in the 1980s likely reflects the coincident rise in breast cancer
      diagnosis via mammography. The recent decline in calendar period trend for white
      women in the United States and for Canadian women may be the result of earlier
      detection and increased use of adjuvant therapy.

PMID- 9017008
TI  - Cigarette advertisement cites journal.

PMID- 9017009
TI  - Re: prediction of carboplatin clearance from standard morphological and
      biological patient characteristics.

PMID- 9017010
TI  - Topical granulocyte-macrophage colony-stimulating factor in patients with cancer
      and impaired wound healing.

PMID- 9017011
TI  - Designer DNA-binding drugs: the crystal structure of a meta-hydroxy analogue of
      Hoechst 33258 bound to d(CGCGAATTCGCG)2.
AB  - An analogue of the DNA binding compound Hoechst 33258, which has the para
      hydroxyl group altered to be at the meta position, together with the replacement
      of one benzimidazole group by pyridylimidazole, has been cocrystallized with the
      dodecanucleotide sequence d(CGCGAATTCGCG)2. The X-ray structure has been
      determined at 2.2 A resolution and refined to an R factor of 20.1%. The ligand
      binds in the minor groove at the sequence 5'-AATTC with the bulky piperazine
      group extending over the CxG base pair. This binding is stabilised by hydrogen
      bonding and numerous close van der Waals contacts to the surface of the groove
      walls. The meta-hydroxyl group was found in two distinct orientations, neither of
      which participates in direct hydrogen bonds to the exocyclic amino group of a
      guanine base. The conformation of the drug differs from that found previously in
      other X-ray structures of Hoechst 33258-DNA complexes. There is significant
      variation between the minor groove widths in the complexes of Hoechst 33258 and
      the meta-hydroxyl derivative as a result of these conformational differences.
      Reasons are discussed for the inability of this derivative to actively recognise
      guanine.

PMID- 9017012
TI  - 1996 AUR Memorial Award. Densitometric analysis of eccentric vascular stenoses:
      comparison of CO2 and iodinated contrast media.
AB  - RATIONALE AND OBJECTIVES: The authors compared the accuracies of CO2 and
      iodinated contrast material in the densitometric quantification of eccentric
      vascular stenoses. METHODS: Five precision-machined eccentric phantom stenoses of
      50%, 60%, 70%, 80%, and 90% cross-sectional area narrowing were integrated into a
      pulsatile ex vivo flow model, imaged with digital subtraction angiography (DSA),
      and analyzed with densitometry. Relationships between the actual and measured
      (densitometric) degree of cross-sectional area narrowing were evaluated by using
      linear regression analysis and paired Student t tests. Comparison measurements
      were obtained in en face and profile projections. In addition, the effect of
      iodinated contrast material concentration was evaluated over a range of dilutions
      (47-282 mg iodine per milliliter). RESULTS: CO2 yielded significantly more
      accurate results than did iodinated contrast material (282 mg iodine per
      milliliter) in the 50%, 60%, and 70% stenosis models when imaging was performed
      en face (P < .005). The best overall correlation was observed with CO2 DSA when
      imaging in profile (slope = 0.91, intercept = 2.42% actual stenosis, r = .99).
      The accuracy of densitometric stenosis estimation was inversely related to the
      concentration of iodinated contrast material. CONCLUSION: CO2 DSA densitometry,
      under the conditions of these experiments, yields quantitative measures of
      relative cross-sectional area narrowing that are comparable with, and under some
      circumstances surpass, those obtained with iodinated contrast material-based DSA.
      In this model, CO2 was more useful than iodinated contrast material in 50%-70%
      stenosis when imaging in the least-optimal plane of stenosis quantification, the
      en face projection.

PMID- 9017013
TI  - 1996 Joseph E. Whitley, MD, Award. Evaluation of an introductory course in chest
      radiology.
AB  - RATIONALE AND OBJECTIVES: The author developed and evaluated the effectiveness of
      an educational program for teaching the fundamentals of chest radiology to
      radiology residents. METHODS: Nineteen radiology residents completed a course
      that consisted of 17 1-hour chest radiology conferences. All seven 1st-year
      radiology residents were required to attend every conference; more senior-level
      residents were encouraged to attend, but their attendance was not mandatory. All
      conferences were given by the same instructor with the use of a didactic slide
      and radiograph presentation, videotape, heart-lung model, and a 120-page
      syllabus. Residents were encouraged to participate in a daily quiz. Resident
      learning was measured by means of a pre- and postcourse examination. RESULTS:
      Conference attendance rate was 93% for 1st-year residents and 75% for more senior
      residents. Nineteen residents took both the pre- and postcourse examination; mean
      scores increased from 65.6% to 86.2% (P < .0001), and course evaluation scores
      were very positive (means ranged from 1.0 to 1.1, with 1 = very good and 5 =
      poor). CONCLUSION: An educational program in chest radiology was developed for
      residents. Both objective and subjective evaluations indicated that resident
      participation in the introductory chest course was an effective means of learning
      the basics of chest radiology. The residents were in support of making this
      course a required part of the residency curriculum.

PMID- 9017014
TI  - Nature of expertise in searching mammograms for breast masses.
AB  - RATIONALE AND OBJECTIVES: The authors investigated how training and experience
      affect the performance of observers searching mammograms for breast masses.
      METHODS: Eye positions of mammographers, mammography technologists, mammography
      residents, and laypersons were compared to scan paths generated by a simulated
      scanner as each searched nine two-view digital mammogram pairs for breast masses.
      RESULTS: Analysis of time-to-hit data revealed that mammographers and mammography
      technologists with the most extensive training and experience had the fastest
      search times in the detection and confirmation of a breast mass on two views.
      Scanning patterns of less-experienced mammography residents were less efficient
      due to wider dispersion of visual attention between potential breast masses and
      perturbations in breast parenchyma. Because laypersons lacked both training and
      experience in mammography, bright blobs in the breast image were considered to be
      intuitively valid target candidates and these features distracted the search by
      capturing visual attention. CONCLUSION: Experience reading normal and abnormal
      mammograms plays a critical role in training radiologists. Experience combined
      with training provides the basis for generating efficient visual search
      strategies and developing distinctive conceptual criteria for perceptual
      differentiation and interpretation of true breast masses from image artifacts and
      structured noise that mimics breast abnormalities.

PMID- 9017015
TI  - Patient perceptions of stereotaxic large-core breast biopsy.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the perceptions of patients who
      underwent stereotaxic core breast biopsy before and after the procedure. METHODS:
      By using a standard questionnaire, 58 patients undergoing stereotaxic core breast
      biopsy with a 14-gauge needle were interviewed immediately before, immediately
      after, and 24 hours and 5 days after the procedure. RESULTS: Discomfort recorded
      by patients 24 hours after core biopsy correlated with the amount of time needed
      before normal activities were resumed (P = .001). Only five patients (9%)
      indicated severe discomfort during the procedure. Patient age, number of core
      biopsy samples taken, and lesion depth did not correlate with level of
      discomfort. Fifty-five patients (95%) resumed normal activities within 24 hours.
      However, 41 patients (71%) had some breast bruising as many as 5 days after the
      procedure. Overall, patient satisfaction with care was high; 56 patients (97%)
      stated they would return for another biopsy in the future. CONCLUSION: The
      morbidity associated with stereotaxic core breast biopsy is low, although the
      majority of patients in this series experienced bruising lasting as long as 5
      days after the procedure. Despite this, almost all patients would return for a
      core breast biopsy in the future, if indicated.

PMID- 9017016
TI  - Improved noninvasive diagnosis of acute pulmonary embolism with optimally
      selected clinical and chest radiographic findings.
AB  - RATIONALE AND OBJECTIVES: The authors improved the noninvasive diagnosis of acute
      pulmonary embolism (PE) by studying the clinical and chest radiographic findings
      of patients suspected of having PE and correlating those findings with the
      physicians' clinical impression. METHODS: A stepwise linear discriminant
      algorithm was developed on the basis of 1,064 patients from the Prospective
      Investigation of Pulmonary Embolism Diagnosis (PIOPED) study to select clinical
      and chest radiographic findings with the highest diagnostic power in patients
      suspected of having PE. Subsequently, a linear classifier and a nonlinear
      artificial neural network were developed to help diagnose PE on the basis of the
      reduced number of findings. RESULTS: Both classifiers produced a statistically
      significant improvement (Az = 0.77 +/- 0.02) in the clinical performance of the
      PIOPED physicians (Az = 0.72 +/- 0.02). Results are also presented separately for
      groups of patients classified on the basis of the difficulty level of their
      ventilation-perfusion lung scans. CONCLUSION: Two computer-aided diagnostic tools
      were developed to assist physicians in the assessment of the pretest likelihood
      of PE by using an optimally reduced number of findings.

PMID- 9017017
TI  - Magnetic resonance detection of acute pulmonary emboli in a canine model with
      pathologic correlation.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the accuracy of magnetic
      resonance (MR) imaging in depicting acute pulmonary emboli at the lobar,
      segmental, and subsegmental levels. METHODS: The authors induced 29 autologous
      emboli in five dogs and confirmed their location with angiography and anatomic
      dissection. MR images obtained with four sequences were independently evaluated
      by two radiologists to detect emboli in each vascular segment. Sensitivities,
      specificities, and accuracies were calculated at segmental and lobar levels.
      RESULTS: The fast short-tau inversion-recovery images provided the greatest
      conspicuity and highest overall accuracy (reader 1 = 74.3%, reader 2 = 80%).
      Accuracy of two-dimensional fast multiplanar spoiled gradient-recalled-echo
      images was limited by spatial resolution (reader 1 = 71.4%, reader 2 = 74.3%).
      The fast spin-echo T2-weighted and spin-echo T1-weighted sequences were
      intermediate in their depiction of acute emboli. Similar results were seen at the
      lobar level. CONCLUSION: MR images depict acute pulmonary embolism at the
      segmental and lobar levels with reasonable accuracy. Fast short-tau inversion
      recovery sequences provided the greatest sensitivity and accuracy.

PMID- 9017018
TI  - Effect of injection speed on the spread of ethanol during experimental liver
      ethanol injections.
AB  - RATIONALE AND OBJECTIVES: Percutaneous ethanol injection therapy may cause
      serious complications, most likely due to the uncontrolled spread of ethanol. The
      authors changed the speed of the injection into postmortem pig livers and
      examined the adverse spread of ethanol from the injection site and the shape and
      size of the resulting lesion. METHODS: One milliliter of 96% ethanol was injected
      into pig livers under sonographic guidance at different speeds (0.075-0.91 mL/s).
      The spread (graded from I to III) and the volumes and shapes of the resulting
      lesions seen after dissection were recorded and correlated with the injection
      speed. RESULTS: When increasing the speed of the injections the large, grade III
      spread increased significantly (P < .01). The lesions created by more rapid
      injection were less spherical than were those created by slower injections (P =
      .08). The volumes of the lesions were not affected by the injection speed.
      CONCLUSION: This experimental model suggests that in percutaneous ethanol
      injection therapy, rapid injection (> 0.3-0.4 mL/s) should be avoided to reduce
      the uncontrolled spread of ethanol. Spherical spreading of ethanol around the
      needle tip is best achieved with slow injection.

PMID- 9017020
TI  - Ignorance is bliss.

PMID- 9017019
TI  - Proton-decoupled phosphorus-31 magnetic resonance spectroscopy in the evaluation
      of native and well-functioning transplanted kidneys.
AB  - RATIONALE AND OBJECTIVES: To evaluate whether decoupling improves signal-to-noise
      ratio and frequency resolution of in vivo kidney spectra, and to compare native
      and well-functioning transplant kidneys. METHODS: Proton decoupling in
      conjunction with three-dimensional chemical shift imaging (3D-CSI) in phosphorus
      31 magnetic resonance (MR) spectroscopy was used with a spatial resolution of 64
      cm3 and 17-minute acquisition time to compare native (n = 10) and well
      functioning transplant (n = 9) kidneys. RESULTS: Proton decoupling improved peak
      amplitudes by almost 30%, as well as chemical shift resolution of in vivo kidney
      spectra. No statistically significant differences in phosphometabolite ratios and
      renal spectra were observed between healthy volunteers and patients with
      nonrejecting transplants. The phosphodiester-phosphomonoester ratio was 3.02 +/-
      0.88, phosphomonoester-inorganic phosphate ratio was 1.07 +/- 0.44, and inorganic
      phosphate-adenosine triphosphate ratio was 0.58 +/- 0.22 after correction for
      saturation effects. CONCLUSION: Improved spectra of native and transplant kidneys
      can be obtained in vivo with MR spectroscopy by using a short acquisition time.

PMID- 9017021
TI  - Health care system reform and its effect on the resident workforce.

PMID- 9017022
TI  - How to succeed in life (and perhaps radiology).

PMID- 9017023
TI  - Seizure-inducing effects of antiepileptic drugs: a review.
AB  - Seizure-inducing effects can be observed in the treatment of epileptic patients
      with antiepileptic drugs (AED). This may be a paradoxical reaction (for example
      the increase of complex focal seizures due to carbamazepine, vigabatrin or
      phenytoin treatment) or a result of AED-induced encephalopathy (commonly induced
      by valproate in patients with complex focal seizures). A seizure increase during
      intoxication with AED is a rare phenomenon, thus, it is not directly related to
      this condition. An incorrect choice of drugs in the treatment of an epileptic
      syndrome or seizure type may provoke seizures (as for example the provocation of
      absences due to carbamazepine or phenytoin). The possible seizure-inducing effect
      of AEDs has to be differentiated from seizure occurrence due to the natural
      course of epilepsy. This may be especially difficult in patients suffering from
      West syndrome or Lennox-Gastaut syndrome, in whom seizure frequency may vary even
      without medication. However, especially in these patients, drug-induced worsening
      of seizure manifestation is often observed. In general, a seizure-inducing effect
      of antiepileptic drugs has to be considered when a seizure increase is observed
      soon after the initiation of therapy, when a stepwise increase of the dosage is
      followed by a further increase of seizures, a decrease of seizures is seen with
      tapering of the dosage and a renewed increase of seizures can be observed after
      this therapy has been reestablished. Finally, one knows that the clinical
      condition of encephalopathy due to valproate or carbamazepine is accompanied by
      seizure increase. In spite of these clinical aspects, the underlying mechanisms
      of seizure increase mostly remain unclear. From animal experiments it is obvious
      that especially carbamazepine and phenytoin may provoke generalized seizures as
      absences or myoclonic seizures. A seizure increase during vigabatrin therapy has
      been attributed to the increase of the cerebral amount of gamma-amino butyric
      acid, which is known to possibly exhibit inhibitory or excitatory neuronal
      effects. The occurrence of tonic seizures in patients with Lennox-Gastaut
      syndrome has been attributed to the sedative effect of the drugs; however, this
      conclusion is controversial. From a clinical point of view, one should consider
      young age of the patient, mental retardation, antiepileptic polytherapy, high
      frequency of seizures or prominent epileptic activity in the electroencephalogram
      previous to medication as risk factors for a possible seizure-inducing effect of
      antiepileptic drugs.

PMID- 9017024
TI  - Quantitative cerebral MRI in epileptic patients.
AB  - OBJECTIVES: To determine cerebral atrophy parameters on MRI images of epileptic
      patients. MATERIAL AND METHODS: Examination of the brain was performed in a 0.5
      Tesla magnet in 32 women with epilepsy and 36 female healthy controls. Fifteen
      patients were classified to have generalised epilepsy and 17 had partial seizure
      onset. Epileptic patients with structural brain changes were excluded. At
      midsagittal level the area of corpus callosum, cerebrum and cerebellum were
      selected as atrophy parameters. At transverse level the ventricle-brain ratio
      (VBR) as a measure of overall cerebral atrophy, bifrontal ratio (BFR) reflecting
      atrophy in the area of the frontal horns, bicaudate ratio (BCR) and bioccipital
      ratio (BOR) were calculated to evaluate atrophy in the region of nucleus caudatus
      as well as in the occipital area. RESULTS: The mean values of VBR were
      significantly larger in the two epileptic groups than in controls, p = 0.0003. No
      significant difference in mean VBR were found between focal and generalised
      seizure onset epilepsy. Also significant decreased cerebellar area on midsagittal
      section was detected in epileptic patients with partial onset epilepsy compared
      with controls, p = 0.037. Atrophy was not associated with type and duration of
      epilepsy, but VBR and age were positively associated in patients with generalised
      onset seizures. CONCLUSION: These findings suggest general brain atrophy to be
      present in epileptic patients including those with partial epilepsy. Whether
      atrophy in epileptic patients occurs as a consequence of disease-related factors
      like hypoxia or treatment with antiepileptic drugs has to be investigated in a
      prospectively designed study.

PMID- 9017025
TI  - Microsomatoagnosia: whole body schema illusion as part of an epileptic aura.
AB  - We report a patient who presented with a whole body microsomatoagnosia as part of
      an epileptic aura. We postulate that this rare phenomenon argues in favor of the
      existence of a whole body integrative neuronal networks which mediates the bodily
      awareness.

PMID- 9017026
TI  - Environmental risk factors in MS: a case-control study in Moscow.
AB  - Environmental influences operating as possible risk factors in MS were studied in
      Moscow. The study included 155 MS patients from the Neurology Departments and the
      outpatient clinics of the First City Hospital of Moscow and 155 controls matched
      for sex, age in 5-year intervals, nationality, and origin (Moscow vs. non
      Moscow). 72.3% of controls were recruited among patients from the same hospital
      as the cases. The remaining controls were volunteers from the hospital staff or
      medical students. Exposures before age 15 were of special interest. MS patients
      reported a higher frequency of: 1) tonsillitis; 2) allergic reactions age 15; 3)
      head trauma below age 16; 4) a predominant meat vs. vegetable diet during
      childhood. Stratified analysis and logistic regression pointed to "meat
      predominance" as the most significant risk factor. Other associations were
      confounded by the respondents' occupations/education.

PMID- 9017027
TI  - Risk factors for multiple sclerosis: a case-control study in Israel.
AB  - This case-control study was aimed at identifying environmental risk factors for
      multiple-sclerosis (MS). Ninety-three Israeli-born MS patients identified in
      country-wide studies and 94 age- and sex-matched controls were interviewed. The
      questionnaire covered a large span of factors at ages 0, 10 and onset of the
      disease, with particular emphasis on socioeconomic status (SES) and sanitary
      conditions (SAN). A significantly larger percentage of patients reported frequent
      respiratory educational levels than controls. The SES and SAN at age 10 were also
      systematically higher among patients, but significance was reached only when the
      frequencies of conditions indicating extremely low values of SES or SAN were
      compared. It is possible that the protective effect of low SES or SAN on risk of
      MS can be detected only when living conditions are well below average, as is
      frequent in developing countries.

PMID- 9017028
TI  - Blood-CSF barrier integrity in multiple sclerosis.
AB  - INTRODUCTION: In about 20% of MS patients an increased CSF/serum albumin quotient
      (QAlb) has been observed. The reason for this blood-CSF barrier dysfunction is
      yet unclear. SUBJECTS AND METHODS: QAlb values from 48 MS patients in relapse
      were correlated with parameters of active CNS lesions as measured by gadolinium
      DTPA MRIs. QAlb values from 20 MS patients without relapse served as controls.
      RESULTS: Mean QAlb values (x 10(3) of a group with spinal cord lesions (7.6 +/-
      3.6; n = 16) differed significantly from those of a control group (4.6 +/- 1.5; n
      = 20; p < 0.005) as well as from those of a group with supratentorial lesions
      (5.0 +/- 1.8; n = 18; p < 0.05), and were higher than those of a group with
      infratentorial lesions (5.8 +/- 2.8; n = 14). QAlb values of patients with a
      spinal lesion tended to decrease with increasing time intervals between onset of
      relapse and lumbar puncture. CONCLUSION: The data is in consent with the present
      knowledge on flow dynamics of both extracellular fluid and CSF. As a clinical
      consequence, increased QAlb values in MS patients may hint at an active spinal
      or, less likely, infratentorial lesion.

PMID- 9017029
TI  - Cerebrospinal fluid nitrate levels in patients with Alzheimer's disease.
AB  - It has been suggested that nitric oxide could be implicated in the pathogenesis
      of Alzheimer's disease (AD). Recently Kuiper et al. reported decreased CSF
      nitrate levels (oxidation product that provides an indirect estimation of nitric
      oxide) in AD patients, assessed with a colorimetric method. However other group,
      using a microplate version of the Griess reaction, did not confirm these
      findings. We studied the CSF and plasma levels of nitrate with kinetic cadmium
      reduction method in 32 AD patients and 36 matched controls. The CSF and plasma
      nitrate levels did not differ significantly between the two study groups. CSF and
      plasma nitrate levels did not correlate with age at onset and duration in the
      patient group. These data suggest that CSF and plasma levels of nitrate are
      apparently unrelated with the risk for AD.

PMID- 9017030
TI  - Leuko-araiosis and stroke: a case-control study.
AB  - OBJECTIVE: Association of leuko-araiosis (LA) with certain risk factors has been
      reported in Western patients. This is a case-control study to determine the risk
      factors and the type of stroke associated with LA in Saudi patients. DESIGN AND
      SETTING: 398 consecutive Saudi patients with the diagnosis of stroke admitted
      over a 6-year period were evaluated for presence or absence of LA on cranial
      computed tomography. LA and non-LA groups were compared with regards to the
      presence of certain risk factors such as type of stroke, age, brain atrophy,
      systemic hypertension and history of cardiac disease or diabetes mellitus. The
      odds ratio and its 95% confidence interval (CI) were used to estimate the
      strength of association between the different parameters. RESULTS: The mean age
      in the LA group was 67.8 +/- 8.5 years as compared to 61.2 +/- 13.2 years in the
      non-LA group. No patient younger than 40 years had LA on CT. Incidence of LA
      increased with age. Forty-seven percent of the LA group were over 70 years of age
      compared to 31% of the non-LA group (OR = 2, CI 1.26-3.15). Generalised atrophy
      was detected in 40% of patients with LA compared to 20% of non-LA group (OR 2.7,
      CI 1.65-4.39). Sixty-nine percent of patients in the LA group had lacunar infarct
      compare to 39% in the non-LA group (OR 3.4, CI 2.15-5.59). The difference was not
      significant between the two groups in relation to the frequency of cerebral
      hemorrhage or larger infarcts. Systemic hypertension was also significantly
      associated with the presence of LA (OR 2.15, CI 1.34-3.43). CONCLUSION: LA is
      associated mainly with lacunar infarcts, cerebral atrophy, systemic hypertension
      and advanced age in Saudi patients.

PMID- 9017031
TI  - Myasthenia gravis and ciprofloxacin.

PMID- 9017032
TI  - Wilson disease: asymptomatic or late-onset type?

PMID- 9017033
TI  - A pitfall in future research?

PMID- 9017034
TI  - Prevalence of diabetic retinopathy in relation to age at onset of the diabetes,
      treatment, duration and glycemic control.
AB  - To study the frequency of diabetic retinopathy in relation to age at diagnosis,
      treatment, duration of diabetes and glycemic control as measured by means of
      HbA1c levels, we performed a cross-sectional, registered-based study in the
      Helsingborg area of southern Sweden, comprising 2232 diabetic patients. Of the
      known diabetic population < 75 years old, approximately 70% were estimated to be
      included. We graded retinopathy according to the alternative classification of
      the Wisconsin study. With an age at diagnosis < 30 years (19% of patients) the
      prevalence of retinopathy was 64%, whereas with an age at diagnosis > or = 30
      years the prevalence of retinopathy was 57% in insulin-treated, and 26% in non
      insulin treated patients. Levels of glycated hemoglobin and duration of diabetes
      were associated with retinopathy in the group with younger onset. In the older
      onset group, there was a relationship between retinopathy and duration of
      diabetes and insulin treatment; glycated hemoglobin had a relationship which was
      of borderline significance with any retinopathy, but clearly significant with the
      pooled group: severe non-proliferative, proliferative retinopathy and/or macular
      edema. Hyperglycemia and duration of diabetes were thus associated with
      retinopathy in both younger- and older-onset diabetes, but hyperglycemia less so
      in the older-onset group.

PMID- 9017035
TI  - Progression of retinopathy is related to glycaemic control even in patients with
      mild diabetes mellitus.
AB  - To study the progression of retinopathy in patients with mild diabetes mellitus,
      we examined, in a cohort study, 347 patients treated with diet alone at baseline.
      The patients participated in an ophthalmological screening and control programme,
      and diet-treated patients who were examined between January 1990 and July 1992
      were included in the study and followed until October 1995. Mean follow-up was
      3.4 +/- 1.1 years. The alternative classification of the Wisconsin study was used
      to classify retinopathy, and the mean HbA1c values for the study period, to
      estimate the level of glycaemic control. At baseline, 314 of the patients (90.5%)
      had no retinopathy, and 33 (9.5%) had mild non-proliferative diabetic
      retinopathy. In 296 patients there was no retinopathy progression, in 27 patients
      there was progression by 1 level in the retinopathy scale, and in 24 patients by
      2 levels or more. In 2 patients there was progression to proliferative diabetic
      retinopathy. The mean HbA1c (%) was 6.5 +/- 1.3. Higher HbA1c correlated to
      increased progression (r = 0.16; p = 0.005), and in a multivariate analysis,
      HbA1c remained associated with a progression of retinopathy by 2 levels or more,
      with a relative risk of 1.4 per percent increase in HbA1c (95% CI 1.1-2.0; p =
      0.02). Furthermore, the presence of any retinopathy at baseline was associated
      with progression with a relative risk of 1.7 (95% confidence interval 1.1-2.8; (p
      = 0.02). These data indicate that even slightly elevated levels of HbA1c might be
      associated with a risk of retinopathy progression.

PMID- 9017036
TI  - Incidence of blindness and visual impairment in diabetic patients participating
      in an ophthalmological control and screening programme.
AB  - We studied the incidence of blindness and visual impairment in patients who were
      enrolled in a photographic control- and screening program for diabetic
      retinopathy. The study cohort consisted of 2133 patients examined between January
      1990 and December 1992 and followed until October 1st 1995. The occurrence of
      blindness (visual acuity < or = 0.1) and moderate visual impairment (visual
      acuity 0.2-0.4) was assessed. The Wisconsin scale was used to grade retinopathy.
      The mean HbA1c value for the last 8 years was used to represent long-term
      glycaemic control. Average follow-up time was 2.9 years. Seven patients were
      blind and 24 had visual impairment caused by retinopathy at the entry of the
      study. Six patients went blind due to retinopathy during the study period,
      corresponding to an incidence of 1.0 per 1000 person-years (95% confidence
      interval 0.4-2.1), and 28 became visually impaired, corresponding to an incidence
      of 4.6 per 1000 person-years (95% confidence interval 3.0-6.6). Multivariate
      analysis showed a statistically significant association between blindness/visual
      impairment and old age, long duration of diabetes, and poor glycaemic control.
      HbA1c values in the highest quartile, i.e. > or = 8.5%, were associated with a
      65% increase in risk of blindness/visual impairment (95% confidence interval 14
      130%). Retinopathy was the major cause of blindness and visual impairment in
      patients with diabetes. The study revealed a low incidence of blindness, which is
      in line with recent reports. Control of hyperglycaemia may be of value for the
      prevention of visual loss.

PMID- 9017037
TI  - Correlation of lens thickness with blood glucose control in diabetes mellitus.
AB  - The aim of this study was to verify if lens thickness in insulin-dependent
      diabetic patients is greater than in non-diabetics, and to establish which
      parameters affect the thickness of the lens age, diabetes duration, glycaemic
      control, insulin dose. Ultrasound biometry and blood glucose measurements were
      taken in 87 patients three times a day: fasting 2 and 4 h after lunch. The
      patient sample was divided into three groups: 30 with no retinopathy, 30
      presented background retinopathy and 27 with proliferative retinopathy; 30 normal
      subjects with a similar age to the diabetic group, comprised the control group.
      No correlation was found between biometric values and blood glucose in the three
      groups (p < 0.05). A significant difference in lens thickness was found in the
      four groups, even after adjusting for age (p < 0.05). Significant differences in
      lens thickness were seen between proliferative retinopathy and the other groups,
      after adjusting for age and duration of diabetes (p < 0.05); lens thickness was
      shown to correlate with diabetes duration (p < 0.05).

PMID- 9017038
TI  - Progressive changes in secondary conformation and composition of the senile
      cataractous human lens capsules.
AB  - The lens capsules of senile cataractous patients were differentiated into three
      progressive grades of immature (I, II and III) and two progressive grades of
      mature (I' and II') groups using Fourier transform infrared (FT-IR)
      microspectroscopy with Fourier self-deconvolution and curve-fitting algorithms,
      according to the changes in IR peak position and its structural composition. The
      secondary conformation of both immature-II and mature-I' cataractous human lens
      capsules was found to change significantly when enhancing the beta-sheet
      structure but simultaneously decreasing the beta-turn structures, as compared
      with the composition of normal human and immature-I cataractous lens capsules.
      The increase in beta-sheet structural proportion might possibly be attributable
      to the age-related cataractogenesis. We also found that the IR peak at 1651 cm-1
      assigned to a-helix shifted to 1647 cm-1 that corresponded to disordered
      structure, but the IR peak at 1662 cm-1 due to beta-turn structure disappeared
      and another new IR peak assigned to alpha-helix structure appeared at 1656 cm-1,
      for both immature-III and mature-II' cataractous lens capsules. It increased the
      compositions of beta-sheet and disorder structures and simultaneously decreased
      the triple helix and beta-turn structures, but maintained the same level in alpha
      helix structure. This suggests that FT-IR microspectroscopy can act as a
      potential tool to exactly differentiate the maturity of senile cataractous human
      lens capsules according to the changes in IR peak position and compositions in
      amide I band.

PMID- 9017039
TI  - Precise correlation of histopathological and fluorescein angiographic morphology
      using retinal vascular casting.
AB  - The histopathology of three eyes obtained post mortem from 2 patients with age
      related macular degeneration was correlated with the pre mortem fluorescein
      angiographic morphology. A precise point-by-point correlation between
      histopathology and the corresponding angiographic appearance was ensured by using
      the cast retinal vascular system as a pattern of reference. The study showed that
      both the photoreceptors, the pigment epithelium, and substances accumulated
      between the retinal and the choroidal vascular systems, may have a blocking
      effect on choroidal background fluorescence as seen on fluorescein angiograms.
      Furthermore, it is confirmed that fluorescein angiographic hyperfluorescence may
      be due to a lack of blocking of the choroidal fluorescence because of a window
      defect in the retinal photoreceptor layer and/or the pigment epithelium.

PMID- 9017040
TI  - The effects of ultraviolet-A radiation on visual evoked potentials in the young
      human eye.
AB  - A recent study from this laboratory using visual evoked potentials (VEPs)
      demonstrated that children's eyes are capable of detecting ultraviolet radiation.
      The aim of this study was to compare dose-response relationships in two age
      groups, 6-10 years (n = 10) and 20-25 years (n = 10). Under photopic viewing
      conditions (550 lux), exposures of monochromatic UV-A (339 nm) and visible
      radiation (502 nm) were correlated to VEPs. The results demonstrate that
      monochromatic UV-A can elicit age and dose dependent responses in the human
      visual system, suggesting that the eyes of children are more responsive to UV
      stimuli than the eyes of young adults.

PMID- 9017041
TI  - The use of single fraction Leksell stereotactic radiosurgery in the treatment of
      uveal melanoma.
AB  - Fourteen patients with posterior uveal melanomas were treated using single
      fraction stereotactic radiosurgery. In each case a dose of 70 Gy was administered
      to the periphery of the tumour. Regression of the tumour has been observed in 13
      patients, whilst the lesion has remained unchanged in one patient. The visual
      acuity has deteriorated in all 14 patients. Significant radiation induced adverse
      reactions were noted in 13 patients and include; retinopathy, optic neuropathy,
      rubeosis iridis, and secondary glaucoma. Two patients have required enucleation
      because of intractable rubeotic glaucoma. One patient has died from proven
      metastases. Although stereotactic radiosurgery appears to be a practical and
      effective method of treating uveal melanomas, its usefulness is limited by a high
      incidence of radiation induced adverse reactions. Further work is required to
      refine the current treatment protocol and establish an optimal prescription dose.

PMID- 9017042
TI  - Clinical status, ocular surface changes and tear ferning in patients with cystic
      fibrosis.
AB  - Twenty-three cystic fibrosis patients and 20 controls were examined for ocular
      surface changes and tear fluid ferning characteristics. The patients were also
      evaluated systemically and given numerical scores according to Schwachman's
      scoring system. Frequency of blepharitis, fluorescein staining, and the
      Schirmer's test values did not differ between patients and controls. Patients
      with cystic fibrosis had a higher frequency of altered ferning pattern that
      corresponded to the disease severity as measured by the Schwachman score (r = 
      0.48, p < 0.05). Although altered ferning pattern was frequent, the rate of type
      I ferning was also high (30%) in patients with cystic fibrosis. We conclude that
      the ferning test should not be used as an aid in diagnosis of cystic fibrosis but
      it may be used as an indicator of clinical status during follow-up.

PMID- 9017043
TI  - The ability of bacteria to use Na-hyaluronate as a nutrient.
AB  - The objective of this study was to test bacteria ability to use Na-hyaluronate as
      a nutrient in vitro. Thirteen bacteria strains were tested in three different
      media: specific culture medium, agar-Healon medium and agar-Healon GV medium. The
      bacterial growth criteria were determined by counting the number of new colonies
      appearing at each observation time (0, 24, 48 and 72 h). The results were
      expressed as the percentage of growth in agar-Na-hyaluronate compared to each
      corresponding specific culture medium. After 24 h in the medium containing agar
      Healon, S. aureus, S. epidermidis, S. pyogenes and S. viridans grew using
      hyaluronic acid as a nutrient. The percentage of growth of these species remained
      constant over the follow-up period. The other bacteria strains tested were unable
      to use Healon as a nutrient. After 24 h of incubation in the medium containing
      agar-Healon GV, S. aureus, S. epidermidis, S. pyogenes, and S. viridans exhibited
      about 20% growth. Subsequently, this percentage slowly increased to about 50%.
      The other bacteria stains tested were unable to employ Healon GV as a nutrient.
      With the exception of Staphylococci and Streptococci, the other species do not
      synthesize the necessary enzymes to break glucosidic bonds, therefore neither
      concentration of hyaluronic acid can be utilized as a source of carbohydrate for
      their survival in culture media.

PMID- 9017044
TI  - Effects of topical dorzolamide on retinal and retrobulbar hemodynamics.
AB  - PURPOSE: Topical carbonic anhydrase inhibitors such as dorzolamide have been
      developed as ocular hypotensive agents devoid of the side effects plaguing their
      systemic predecessors. We evaluated the influence of dorzolamide on retinal and
      retrobulbar blood flow markers to determine if the drug has orbital vascular as
      well as ocular hypotensive effects. METHODS: Eleven persons with healthy eyes
      received either placebo or two drops 2% dorzolamide, 2 h prior to studies
      conducted in double-masked, counterbalanced fashion. Four retrobulbar vessels
      (nasal and temporal posterior ciliary, central retinal, and ophthalmic arteries)
      were analyzed by color Doppler imaging; scanning laser ophthalmoscopy was used to
      examined retinal and superficial optic nerve head blood linear velocity. RESULTS:
      Dorzolamide lowered IOP from 15.7 +/- 0.7 to 13.7 +/- 0.7 mmHg (p < 0.05). The
      drug also hastened retinal arteriovenous passage of fluorescein dye, and
      accelerated capillary dye transit in the macula and optic nerve head. The drug,
      however, left unaltered blood velocity or resistance index in any retrobulbar
      vessel. CONCLUSIONS: Dorzolamide is an effective ocular hypotensive agent that
      accelerates blood velocity in the retinal and superficial optic nerve head
      without an apparent effect upon retrobulbar hemodynamics.

PMID- 9017045
TI  - Structural evidence for membrane lipid changes in human cataract.
AB  - Lipid changes in relationship to cataractogenesis were studied with histochemical
      methods (topoptical reactions) of polarization microscopy. Frozen section of
      formaldehyde-fixed human lenses were used for these studies. Six lenses were
      transparent and 14 lenses presented early to confluent cortical opacities. Cell
      membrane lipids of transparent lenses showed 8.0 +/- 2.7 nm light retardation. In
      the early cataractous lenses the light retardation of cell membranes was 23.3 +/-
      5.0 nm and that of the fusiform and globular lipids was 37.7 +/- 4.0 nm and 48.5
      +/- 6.9 mn, respectively. In the non transparent cortical regions of cataractous
      lenses, membrane lipids were not observed. Similar to other cell membranes,
      normal lens membranes are composed of loosely organized lipids. In early cataract
      lipid density uniformly increased along the cell membranes at the clinically
      transparent areas, while at the areas with clinically evident fine opacities,
      small fusiform and globuler lipid drops were formed by even more dense lipids.
      Confluent cortical cataracts were associated with disappearance of membrane
      lipids. In our study our findings demonstrated intramembrane lipid changes
      associated with cataractogenesis.

PMID- 9017046
TI  - Quantitative assessment of fixational eye movements by scanning laser
      ophthalmoscopy.
AB  - A new method for quantifying fixational eye movements by scanning laser
      ophthalmoscopy was developed and the method was evaluated in ten normal persons.
      Video sequences of the ocular fundus obtained during fixation were recorded, and
      linear movements of the fovea between successive video frames were transformed to
      angular movements of the eye by an algorithm that takes into account the
      individual optical properties of the eye. A computer program was developed to
      automatically calculate the amplitude, the direction, and the duration of the
      angular movements together with the precision of each of these estimates. Two
      types of eye movements could be recognized in normal persons; a fast type
      (saccades) which was initiated and terminated within one video frame (20 msec),
      and a slow type (drifts) which lasted more than 8 video frames (160 msec). The
      mean amplitude of the fast movements (0.41 degrees) was significantly higher than
      the mean amplitude of the slow movements (0.31 degrees). The methods was found to
      be suitable for quantifying fixational eye movements in clinical trials while
      simultaneously visualizing the ocular fundus. However, by refining the
      determination of the foveal position on the SLO images the precision of the
      method can be further improved.

PMID- 9017047
TI  - Risk factors for graft failure in penetrating keratoplasty.
AB  - We clarified the preoperative risk factors for graft failure in penetrating
      keratoplasty with fresh donor corneas. This analysis covered 698 consecutive
      keratoplasty cases in a single center between 1971 and 1992, and was designed to
      assess the risk factors. The risk factors in penetrating keratoplasty were
      determined by the Cox multiple regression model which considers the follow-up
      periods and multiple factors simultaneously. The factors which worsen the
      prognosis of keratoplasty significantly were found to be preoperative endothelial
      dysfunction (hazard ratio = 2.3), prior glaucoma/ocular hypertension (hazard
      ratio = 2.0), preoperative corneal vascularization (hazard ratio for within one
      quadrant = 1.3, hazard ratio for 2 or more quadrants = 1.6), anterior synechiae
      of iris (hazard ratio = 1.5), aphakia or pseudophakia (hazard ratio = 1.4), and
      older donor age (hazard ratio = 1.3 in proportion to the increase of each 10-year
      period of age). Surgeons must take these risk factors into consideration to
      obtain a better prognosis for keratoplasty.

PMID- 9017048
TI  - Women and men--same eyes?
AB  - In ophthalmology, few studies have been designed to investigate possible
      differences between women and men in a consistent manner. Some evidence is,
      however, available showing significance male-female differences. The importance
      of gender in ophthalmological research is emphasized by focusing on some
      knowledge about sex differences in ocular components in relation to cataract
      surgery and on the influence of the female hormones on the cornea.

PMID- 9017049
TI  - Acanthamoeba keratitis in the south of Sweden.
AB  - Eight patients with Acanthamoeba keratitis were diagnosed and treated at our
      clinic between February 1991 and February 1993. Five of these were contact lens
      wearers, two had suffered recent corneal trauma and one had recently undergone
      penetrating keratoplasty. The diagnoses were based on both culture and
      histological examination of biopsy material in three cases, on culture alone in
      two cases and on histological examination alone in three cases. In all but one
      primary treatment was Propamidine isethionate and Neomycin/Polymyxin B topically
      and Ketoconazole orally. Because of poor healing three patients additionally
      received Paromomycin and Miconazole or Clotrimazol topically; two of these were
      further treated with Polyhexamethylene biguanide topically. The interval from
      initial symptoms to accurate diagnoses varied from one to eleven months. In one
      patient the eye could not be saved; in the remaining patients visual acuity after
      healing ranged from hand movements to 1.0.

PMID- 9017050
TI  - Visual impairment and general health among Danish cataract patients. Results from
      the Danish Cataract Surgery Outcomes Study. I.
AB  - This Danish multicenter study was undertaken to evaluate current indications for
      cataract extraction and to compare the heath status among patients enlisted for
      cataract surgery with that reported for the background population. A consecutive
      sample of 290 patients from all ophthalmic hospital departments in Denmark was
      examined and interviewed prior to cataract extraction. The mean visual acuity in
      the eye enlisted for surgery was 0.17. A visual acuity of < 0.05 occurred in
      11.1% and 46.7% had a visual acuity of > or = 0.05 to 0.3. Comparing these
      figures to other recent European studies it seems reasonable to conclude that in
      Denmark surgery is performed at an earlier stage of the disease. Only a few
      patients with no functional impairment were seen; other appropriate indications
      for surgery were seen for these patients. Occurrence of angina, bronchitis and
      prior myocardial infarction was higher in the cataract sample as compared to the
      random sample of Danes. The likelihood of preferring an outpatient procedure was
      significantly increased among younger patients, patients of better general health
      and among patients with better pre-operative visual acuity in eye enlisted for
      surgery.

PMID- 9017051
TI  - Changing threshold for cataract surgery in Denmark between 1980 and 1992. Results
      from the Danish Cataract Surgery Outcomes Study. II.
AB  - In Denmark the number of cataract extractions has increased 350% from 1980 to
      1991. During the same period the elderly population at risk has only increased
      17%, and thus cannot account for the large increase in the number of extractions.
      In order to investigate whether more comprehensive clinical indications could be
      a possible explanation, we compared pre-operative visual acuity and visual
      impairment in two consecutive samples of Danish cataract surgery patients
      obtained in 1980 (n = 73) and in 1992 (n = 290). Criteria for inclusion were
      similar and both samples were representative for the whole country. During the
      period mean pre-operative visual acuity increased from 0.04 to 0.16 in the eye
      enlisted for surgery (p < 0.00001). Visual functional impairment could be
      compared by using the same questionnaire for patient interview in 1992 as was
      used in 1980. In 1992 the degree of impairment was significantly less for
      reading, outdoor orientation and self care activities. A change in surgical
      threshold or clinical indications for surgery appears to be a major contributing
      factor to the large increase in surgical rates, even though a trend to perform
      second eye cataract surgery more often might also be of some importance.

PMID- 9017052
TI  - Indications for cataract surgery in a Danish county 1980 and 1990.
AB  - From 1980 to 1990 the number of cataract extractions in our department increased
      from 268 to 827, i.e. 209% within the same referral area. A review was made to
      see if the indications for cataract extraction had changed in that period. The
      increase in frequency of cataract extractions was statistically significant in
      all age groups except males aged 60-69. The increase was most noticeable in the
      older age groups. Preoperative visual activities were moderately higher in 1990
      compared with 1980. The frequency of second eye surgery did not change in the
      period. Females had in 1980 as in 1990 a higher frequency of cataract extractions
      than males in all age groups > 60 years.

PMID- 9017053
TI  - Ocular findings in the Laurence-Moon-Bardet-Biedl syndrome.
AB  - PURPOSE: To improve the description of the ocular part of the Laurence-Moon
      Bardet-Biedl syndrome. METHODS: We examined 44 Scandinavian individuals who all
      had retinal dystrophy plus at least 2 more of the traditional cardinal signs of
      the syndrome: obesity, hypogenitalism, polydactyly and mental retardation.
      RESULTS: Full-field electroretinograms were obtained in 36 of the individuals and
      were abnormal in all. The dark adaptation thresholds were elevated by on average
      3.5 log units. Symptoms of night blindness were observed at a mean age of 4 years
      and visual problems at daytime at 6-7 years. No one exceeding the age of 16 had a
      best corrected visual acuity of more than 0.1. In the fundus attenuated vessels
      were noted at all ages while macular pigmentations and a wax-pale optic disc
      appeared at age 6-7 years. Pigmentary changes in the midperiphery were noted at
      the earliest at 13 years of age and appeared mainly as bone spicules, however, in
      a minority of cases the pigmentations were atypical. Ten of the participants had
      been followed through a period of 9 years. Their visual acuity was reduced by on
      average 0.3 line (decimals) and the angle of visual fields by approximate 3
      degrees (Goldmann standard object V:4e) per year through the adolescence.
      CONCLUSION: The ocular disease in Laurence-Mood-Bardet-Biedl syndrome presents
      early, the prognosis for visual function is poor and the fundus features are
      atypical and varying.

PMID- 9017054
TI  - Full-field electroretinograms in individuals with the Laurence-Mood-Bardet-Biedl
      syndrome.
AB  - PURPOSE: To evaluate rod and cone function in individuals with the Laurence-Moon
      Bardet-Biedl syndrome. METHODS: We obtained a full-field electroretinograms in 36
      patients. If responses less than 10 microV were recorded with single white
      flashes a special techniques with narrow band filter and computer averaging was
      used. RESULTS: No rod responses to dim blue light could be obtained in any of the
      patients. Residual cone flicker responses were measurable in 28 of the
      individuals. Those with amplitudes < 0.05 microV were significantly older than
      those with amplitudes > 1.00 microV. The ERG pattern was consistent within
      affected pairs of siblings in 8 families. CONCLUSION: The retinal dystrophy in
      Laurence-Moon-Bardet-Biedl syndrome is primarily a rod-cone dystrophy, but even
      cone flicker amplitudes are severely reduced with further progression with age.
      There is no intrafamilial variability of the electroretinograms in affected
      siblings.

PMID- 9017055
TI  - Ocular characteristics in nephropathia epidemica or Puumala virus infection.
AB  - PURPOSE: We documented the largest series so far concerning the ocular
      characteristics of nephropathia epidemica. METHODS: A total of 37 consecutive
      nephropathia epidemica patients underwent a comprehensive ophthalmic examination
      during hospitalization for systemic infection, and a control examination after
      recovery. RESULTS: The most common ocular symptoms were: frontal headache or
      periocular pain (75.6%), blurred vision (54.1%) and photophobia (10.8%). The best
      corrected visual acuity of 7 patients (18.9%) was reduced during the acute phase
      as compared to the later control examination. Myopic shift was found in 15
      patients (40.5%), three of whom (8.1%) developed real transient myopia. There
      were no attacks of angle closure glaucoma in this series. On the contrary, the
      intraocular pressure was decreased in 49 eyes (66.2%) during the acute stage of
      the disease. Lid edema was present in 28 eyes (37.8%), conjunctival injection in
      20 eyes (27.0%), chemosis in 8 eyes (10.8%) and subconjuctival bleeding in 3 eyes
      (4.1%). Signs of acute anterior uveitis were found in 10 eyes (13.5%), however,
      this resolved without treatment. In one eye retinal edema with hemorrhages was
      detected. Ultrasonography revealed narrowing of the anterior chamber during the
      acute phase in 69 eyes (93.2%) and thickening of the crystalline lens in 64 eyes
      (86.5%). CONCLUSION: Ophthalmic findings in nephropathia epidemica are not
      uncommon. The symmetry of the clinical manifestations reflects the systemic
      nature of the underlying infection.

PMID- 9017057
TI  - VDU work: longitudinal survey on refractive defects.
AB  - A longitudinal survey in two different phases with an interval of 4 years
      (including more than 23,000 employees) has been carried out to study whether the
      time spent using VDU (daily hours and years of work) can change the refractive
      state. With reference to the whole sample including all refractions, there was no
      significant difference in the refractive state in employees who spent varying
      daily hours or years working at VDU. Furthermore, there were no significant
      changes in the refractive states of emmetropic, hypermetropic and myopic
      subjects, with regard to the time spent working at VDU. The data have shown that
      a high exposure to VDU work (more than 6 h per day or more than 6 years spent
      working at a VDU) is not responsible for inducing or worsening refractive error.

PMID- 9017056
TI  - A comparison of Healon and Amvisc on the early postoperative pressure after
      extracapsular cataract extraction with implantation of posterior chamber lens.
AB  - Two viscoelastic agents, Healon and Amvisc, both hyaluronic acids, were evaluated
      in two prospective, randomized and masked studies in order to compare the effects
      of the viscoelastics and timolol (Blocadren ) on the early postoperative
      intraocular pressure (IOP) after planned extracapsular cataract extraction with
      implantation of a posterior chamber lens. The study protocols were similar,
      especially with regard to the sample size, pre-, per- and postoperative
      management and sampling. The IOP was measured preoperatively, 3-6 and 24 h
      postoperatively. The testing of Amvisc revealed that aspiration or non-aspiration
      of Amvisc at the end of surgery was of little importance for the IOP, and that
      timolol significantly reduced the IOP 3-6 h postoperatively in the order of about
      8 mmHg. The postoperative IOP was lower for Amvisc than for Healon only when the
      viscoelastic material was aspirated and topical timolol was administered. In all
      the other groups there were no significant differences between the viscoelastics
      as far as the postoperative pressure was concerned. Multiple regression revealed
      a marked pressure reducing effect of timolol 3-6 h postoperatively in both
      groups, but no effect was observed 24 h postoperatively. The two viscoelastic
      agents showed minor effect on the IOP both 3-6 and 24 h postoperatively.

PMID- 9017058
TI  - Full-field electroretinograms in a family with Mohr-Tranebjaerg syndrome.
AB  - A family with a newly detected X-linked syndrome including sensorineural
      deafness, mental retardation, dystonia and blindness was examined with full-field
      electroretinography in order to order to find out if the blindness was caused by
      a retinal degeneration. Six affected males and 2 obligate carriers showed no
      signs of retinal degeneration. One of 7 affected males had central areolar
      choroidal dystrophy confirmed by central scotomas in visual fields and an
      electroretinographic pattern consisting of an attenuated amplitude as well as a
      prolonged implicit time of the cone b-wave on stimulation with 30 Hz flickering
      white light.

PMID- 9017059
TI  - Strabismus in children with cerebral palsy.
AB  - In 48 children with cerebral palsy the characteristics of the squint and
      amblyopia were analyzed, also with respect to the features of cerebral palsy and
      to birth weight. Strabismus of congenital esotropia type was found to be common,
      as was also exotropia of early onset. Spontaneous alternation or an accommodative
      component of the squint was present only in a few cases. There was no evidence of
      an accumulation of any strabismus type in the different subgroups of cerebral
      palsy, whereas amblyopia or an obvious risk for amblyopia was found in the great
      majority of the cases. Some kind of amblyopia treatment was given to 34. Most of
      them showed improvement of the visual capacity which encourages treatment of
      amblyopia, even in children with cerebral palsy.

PMID- 9017060
TI  - Central areolar choroidal dystrophy and slowly progressive sensorineural hearing
      loss.
AB  - Central areolar choroidal dystrophy (CACD) is a rare hereditary disorder leading
      to a central scotoma in middle-aged patients. Two cases of CACD in association
      with perceptive hearing loss are discussed. A 62-year-old male and a 51-year-old
      female patient complained of visual deterioration and subsequent hearing loss
      over several years. In addition to routine ophthalmic and otorhinolaryngological
      examination both patients underwent fluorescein angiography,
      (electro)physiological examination and audiometry examination. A demarcated area
      of atrophy of pigment epithelium and choriocapillaris was found in both patients.
      A slowly progressive sensorineural hearing loss after adolescence was found in
      both patients. The hearing deteriorated to such a level at middle age that
      hearing aids were necessary. These two cases show that CACD may be associated
      with perceptive hearing loss.

PMID- 9017061
TI  - Recurrence of climatic droplet keratopathy. Two case reports.
AB  - Climatic droplet keratopathy (CDK) is characterized by a band-shaped pattern of
      subepithelial opacities and golden-yellow spherules. Recurrence of this disease
      in corneal grafts has not been reported. We report two cases that developed
      recurrence of this disease in corneal grafts done for CDK, 3 1/2 years following
      lamellar penetrating keratoplasty and 6 years following penetrating keratoplasty.
      This illustrates the possibility of this degenerative disease to recur in a few
      years if aetiological factors are persistently present.

PMID- 9017062
TI  - Oculomotor findings in preterm children with periventricular leukomalacia. A
      connection between lesions in the periventricular area and eye motility
      disorders?

PMID- 9017063
TI  - Pathological cupping in normal pressure glaucoma is probably not due to low CSF
      pressure.

PMID- 9017064
TI  - Hearing assessment in children with stapedius reflex threshold measurements--an
      alternative objective approach.

PMID- 9017065
TI  - Speech must always be taught.

PMID- 9017066
TI  - An ear and hearing survey in northeast Thailand by the Bangkok Otological Center,
      Siriraj Hospital, Mahidol University.

PMID- 9017067
TI  - Open-type congenital cholesteatoma.

PMID- 9017068
TI  - Tympanoplasty on the only hearing ear with chronic otitis media.

PMID- 9017069
TI  - Treatment of the draining mastoid cavity.

PMID- 9017070
TI  - Persistent pattern of variations in thickness of the human nasal septum:
      implications for stress and trauma as illustrated by a complex fracture in a 4
      year-old boy.

PMID- 9017071
TI  - Nasal cartilage maturation assessed by automated computer-assisted image
      analysis.

PMID- 9017073
TI  - Modern management of allergic rhinitis.

PMID- 9017072
TI  - Acoustic rhinometry--predictive value in septal and turbinate surgery.

PMID- 9017074
TI  - Immediate transnasal endoscopic duroplasty for acute cerebrospinal fluid
      rhinorrhea.

PMID- 9017075
TI  - New concepts in nasal evaluation.

PMID- 9017076
TI  - 'Regular' versus 'as required' use of azelastine nasal spray in the treatment of
      seasonal allergic rhinitis.

PMID- 9017078
TI  - Perception of speech--normal and abnormal.

PMID- 9017077
TI  - Role of azelastine nasal spray in the symptomatic treatment of seasonal allergic
      rhinitis.

PMID- 9017079
TI  - Surgical treatment of oral cavity carcinomas.

PMID- 9017080
TI  - Cisapride in the treatment of globus hystericus.

PMID- 9017082
TI  - Effects of maternal mental retardation and poverty on intellectual, academic, and
      behavioral status of school-age children.
AB  - The impact of low maternal IQ and poverty was examined through comparison of 27
      school-age children of mothers with mild mental retardation to 25 similarly
      impoverished children of mothers without mental retardation. The children whose
      mothers had mental retardation had lower IQs and academic achievement and more
      behavior problems. Not one child with a mother who had mental retardation was
      problem-free. Boys were affected more severely than were girls. Quality of the
      home environment and maternal social supports were lower in the group with
      maternal mental retardation; both measures were negatively correlated with child
      behavior disorders. Results suggest that being raised by a mother with mental
      retardation can have detrimental effects on child development that cannot be
      attributed to poverty alone.

PMID- 9017081
TI  - Comparison of socially accepted and rejected children with mental retardation.
AB  - The influence of social behavior and social cognitive skills on social status of
      children with mental retardation was investigated by comparing socially accepted
      and socially rejected children. A sociometric survey conducted with 764 children
      in 34 regular education classrooms identified 20 socially accepted and 20
      socially rejected students with mental retardation. Accepted children displayed a
      higher level of social behavior and a lower level of sensitive-isolated behavior.
      The two groups also differed in their social cognitive skills. In response to
      social problems, accepted children chose friendly-submissive goals and generated
      a low rate of positive outgoing strategies, whereas rejected children chose
      friendly-assertive goals and generated a high rate of positive outgoing
      strategies. Findings point to the value of examining differences between children
      with mental retardation who are accepted and rejected in inclusive settings and
      underscore the importance of social behavior and social cognitive skills in the
      acceptance-rejection process.

PMID- 9017083
TI  - Stability and change over time in cognitive level of children with delays.
AB  - Cognitive and family data on 82 children with developmental delays were collected
      in an 8-year longitudinal study. Child measures included the Gesell and the UCLA
      Temperament Scale administered at child age 3 and the Stanford Binet,
      administered at child ages 6 and 11. Family measures included SES, level of
      maternal education, and factor scores reflecting family accommodation or
      adaptation at the three time points. Although cognitive scores for the group were
      stable, use of a random coefficient regression technique documented differences
      in the decline of cognitive scores over time. Examination of change scores
      identified increasing, stable, and decreasing patterns of change. There were
      significant correlations between change in IQ, entering DQ, and Easy and
      Difficult temperaments.

PMID- 9017084
TI  - Food- and nonfood-related differential outcomes in equivalence learning by adults
      with Prader-Willi syndrome.
AB  - Adults with Prader-Willi syndrome learned the conditional relations necessary for
      the formation of two equivalence classes under four conditions: (a)
      nondifferential, nonedible outcomes; (b) nondifferential, edible outcomes; (c)
      differential, nonedible outcomes; and (d) differential, edible outcomes. Tests
      for transitive relations revealed superior performance when the two differential
      outcomes procedures, in which a distinct reinforcer was associated with each
      stimulus set, were used during teaching. Performance on test trials following
      nondifferential outcomes training was better when edible outcomes were used
      during teaching for 4 of the 5 participants. An enhancement of performance on the
      derived relations separated by two or three nodal stimuli was seen when a
      differential outcomes procedure was used to teach the baseline conditional
      relations.

PMID- 9017085
TI  - Meta-analytic study on treatment effectiveness for problem behaviors with
      individuals who have mental retardation.
AB  - Meta-analysis of 482 empirical studies on treatment of problem behaviors of
      individuals with mental retardation was conducted. A metric of treatment
      effectiveness was computed for 1,451 comparisons between baselines and
      treatments, 34 topographies of problem behavior, and 64 treatment procedures.
      Analysis of variance with percentage of nonoverlapping data as the dependent
      variable and comparison as the basic unit of analysis revealed that treatment of
      externally destructive behaviors had significantly lower mean percentage of
      nonoverlapping data scores than did treatment of socially disruptive and
      internally maladaptive behaviors. Response contingent procedures were
      significantly more effective than were other procedures. No significant
      interactions were found. Results of a stepwise regression showed that only
      performing a functional analysis made a significant contribution. These results
      may lead to more objective assignment of treatment procedures to problem
      behaviors.

PMID- 9017086
TI  - Prospective study of the prevalence of Alzheimer-type dementia in
      institutionalized individuals with Down syndrome.
AB  - Institutionalized patients with Down syndrome (n = 307) were monitored for 5 to
      10 years prospectively to determine prevalence of Alzheimer-type dementia.
      Clinical signs, cognitive functioning, and EEGs were assessed. When possible,
      postmortem neuropathological examinations were conducted. Progressive mental and
      physical deterioration was found for 56 of the residents. Mean age at onset of
      dementia was 56 years. Prevalence increased from 11% between ages 40 and 49 to
      77% between 60 and 69. All patients 70 and over had dementia. Neuropathological
      findings were consistent with clinical diagnosis. Use of a dementia checklist,
      cognitive skills inventory, and EEG reliably detected Alzheimer-type dementia at
      an early stage.

PMID- 9017087
TI  - Akathisia in adults with mental retardation: development of the Akathisia Ratings
      of Movement Scale (ARMS).
AB  - We developed an akathisia rating scale for use with persons who have mental
      retardation and screened for the occurrence of akathisia in three samples: 66
      adults receiving maintenance neuroleptic treatment, 20 adults not receiving
      neuroleptics, and 8 adults undergoing neuroleptic dose reduction. The scale had
      an acceptable level of interrater reliability and validly measured group
      differences related to neuroleptic treatment status. Using an empirically derived
      cut-off-score, we estimated the prevalence rate for akathisia to be 5% in
      neuroleptic-free subjects, 17% in neuroleptic-maintenance subjects, and 25% in
      neuroleptic-reduction subjects. Akathisia, dyskinesia, and stereotypy manifested
      as qualitatively different movement topograhies. The occurrence of dyskinesia
      stereotyped movement disorder was associated significantly with an increased
      occurrence of akathisia.

PMID- 9017088
TI  - Mortality: an individual or aggregate variable?

PMID- 9017089
TI  - Ovarian stimulation in assisted reproduction.
AB  - In assisted reproductive medicine the controlled ovarian hyperstimulation enables
      several oocytes to be collected with the following transfer of more than one
      embryo and a higher pregnancy rate than in natural cycles. The most frequently
      used stimulation protocols are: i) clomiphene citrate (CC) and hMG stimulation;
      ii) hMG/FSH stimulation; iii) GnRH agonist (GnRH-a) and hMG/FSH stimulation,
      iiia) GnRH-a long protocol, iiib) GnRH-a short protocol, GnRH-a ultrashort
      protocol, iv) GnRH antagonist and hMG stimulation. The protocols are described
      and the advantages and disadvantages are discussed.

PMID- 9017090
TI  - Generation of antisera against mouse and human synthetic ZP3 peptides.
AB  - The ZP3 protein is a zona pellucida glycoprotein which plays a major role in
      sperm binding and induction of the acrosome reaction. ZP3 proteins occur in
      various mammalian zonae pellucidae; their primary structures are highly conserved
      as revealed by cDNA cloning. We generated antisera against synthetic peptides
      that are specific either for mouse ZP3 (AS ZP3-9) or for human ZP3 (AS ZP3-14).
      The antisera specifically recognized their respective peptide employed as
      immunogen and did not cross-react with control peptides. AS ZP3-9 detected ZP3
      protein in isolated mouse zona pellucida and oocytes, whereas AS ZP3-14 did not
      react with proteins in murine egg cells or zona pellucida. Our results indicate
      that antisera against synthetic ZP3 peptides can be used as specific markers for
      the identification of individual ZP3 proteins in mouse and human oocytes. The
      antisera might be useful tools for the evaluation of ZP3 location and function.

PMID- 9017091
TI  - Contribution of andrological factors to sterility.
AB  - Male fertility disorders contribute to sterility by inhibiting conception. The
      prevalence in general, is high, nearly 5% of men are subfertile or infertile.
      Infertility could be diagnosed in some cases by specific investigations, however,
      a positive prediction of fertility is not possible. Nearly half of the couples
      could be treated successfully. It should be recognized, however, that
      psychosocial assistance is one of the most important tasks of modern reproductive
      medicine for couples in whom the treatment was not successful.

PMID- 9017092
TI  - Y chromosome microdeletions and male subfertility.
AB  - Men with azoospermia and severe oligozoospermia have been investigated by
      molecular probing of the long arm of the Y chromosome. We find microdeletions
      affecting various parts of the long arm of the Y chromosome in approximately 10%
      of men with non-obstructive azoospermia and severe oligozoospermia but not in a
      fertile comparison population. This work needs further confirmation in different
      countries and different racial groups but it would appear that microdeletions
      (and presumably genetic defects) are commonly associated with defects of
      spermatogenesis. These findings have implications for the management of severe
      male subfertility with in vitro fertilization/intracytoplasmic sperm injection.

PMID- 9017093
TI  - Male infertility treatment in the light of evidence-based medicine.
AB  - A new scientific paradigm in medicine has emerged over the last decades,
      summarized under the term of 'evidence-based medicine'. It emphasizes that
      therapies derived from pathophysiological concepts must be confirmed and
      therapeutic decisions be backed by a systematic clinical observation. Since the
      quality of data revealed and the evidence for conclusion will depend upon the
      design of the study, general principles concerning randomized, controlled
      clinical fertility trials will be described as the hallmark of high-quality
      studies. Therapies for male infertility will be discussed in terms of the studies
      they are based on, and to what extent the paradigm of evidence-based medicine has
      entered the field of andrology will be has entered the field of andrology will be
      considered critically.

PMID- 9017094
TI  - Critical evaluation of the effectiveness of different modes of treatment of male
      infertility.
AB  - Among cohorts of couples treated for infertility due to a male factor it is the
      effective cumulative rate of successful deliveries and the cost per delivery that
      must be considered in assessing the value of different modes of treatment. The
      'wait and see', timed coitus, or counselling approach has a low success rate
      (about 15% in 12 months), and a relatively high cost per delivery because of the
      cost of control visits and of tests for the prediction of ovulation. The high
      success rate of varicocele treatment (35% in 12 months, between 60 and 80% after
      24 months), and the moderate cost of retrograde venography and embolisation
      results in a low cost per delivery. This cost is the lowest in anti-oestrogen
      treatment of idiopathic oligozoospermia, with a 20-30% effective cumulative
      pregnancy rate in 6 months. Three months of intra-uterine insemination (IUI) of
      Percoll gradient selected spermatozoa has a higher effective cumulative success
      rate than conventional in vitro fertilization (IVF) applied in cases with similar
      sperm characteristics, and the cost per successful delivery of the former is
      eight times lower than that of the latter. Intracytoplasmic sperm injection can
      successfully be applied in cases with more severe sperm deficiency; it has a
      higher success rate than conventional IVF, and is slightly more cost-efficient.
      However, the effective cumulative pregnancy rate remains relatively low (about
      45% in 12 months) because of the high drop-out rate and long time interval
      between treatment cycles among unsuccessful couples.

PMID- 9017095
TI  - Assisted fertilization--treatment of severe male subfertility.
AB  - Since 1992 direct injection of a single spermatozoon into the cytoplasm of the
      oocyte (ICSI) has developed as the treatment of choice in cases of severe male
      subfertility. The ICSI procedure displays high fertilization and pregnancy rates
      in cases of extreme oligoasthenoteratozoospermia. In combination with sperm
      aspiration from the epididymis or sperm retrieval by testicular sperm extraction,
      fertilization is possible even in cases of azoospermia. To date, a couple of
      thousand children have been born after ICSI. Despite the criticism about the lack
      of natural selection while breaking the zona pellucida and the cytoplasmic
      membrane with the injection pipette, there has been no increased incidence of
      malformations and chromosomal abnormalities.

PMID- 9017096
TI  - Psychological aspects in the therapy of the andrological sterility factor with
      regard to the unfulfilled wish for a child.
AB  - Aside from knowledge of the respective causes in women and men, the therapy of
      couples with unfulfilled wish for a child requires the patients' willingness to
      submit to treatment. From a psychological point of view, the extent of the
      suffering is focused on, to be presupposition of the patients' compliance.
      Results from various research groups suggest that men tend to portray themselves
      as being especially unstressed. In the following report, considerations about the
      consequences to the doctor-patient relationships in andrology will be depicted.
      Among other things, the problematic relationship between the men affected and
      their fathers will be discussed as a possible cause of the self images of these
      men.

PMID- 9017097
TI  - Epididymis and sperm function.

PMID- 9017098
TI  - Analysis of intra-operative aspirates taken during microsurgical refertilization
      in obstructive azoospermia--preliminary results. The BMFT Study Group for
      Microsurgery, Giessen.
AB  - The reasons for the discrepancy between 'patency' and 'pregnancy' in the outcome
      of microsurgical refertilization are partially unknown. The quality of the intra
      operative aspirate and of the spermatozoa at the level of the anastomosis are
      discussed worldwide as important factors influencing the success of fertilization
      in the case of post-operative patency. In 152 men undergoing microsurgical
      refertilization (vasovasostomy, tubulovasostomy, microsurgical epididymal sperm
      aspiration, transurethral resection of the ejaculatory duct), 281 aspirates were
      classified intra-operatively according to Silber, and post-operatively using the
      Shorr staining technique. In 62 aspirates a computer-aided sperm analysis (CASA)
      was performed. The percentage of intact spermatozoa decreased from 94.9% at the
      caput to 9.4% at the cauda epididymidis. The post-operative classification
      demonstrated an acceptable correlation (0.71) to all grades of intraoperative
      classification. There was a good correspondence in Silber 4 and 5 but worse in
      Silber 1 and 2. In CASA, the percentage of motile spermatozoa was not different
      between epididymal and post-epididymal aspirates. Furthermore, velocity
      parameters did not differ significantly, but there was a significantly higher
      straightness of post-epididymal spermatozoa in comparison to epididymal
      spermatozoa.

PMID- 9017099
TI  - Results of microsurgical epididymal sperm aspiration (MESA) ans testicular sperm
      extraction (TESE) in azoospermic men using intracytoplasmic sperm injection
      (ICSI).
AB  - The rationale and results of using epididymal and testicular spermatozoa with
      intracytoplasmic sperm injection (ICSI) for zoospermic patients are reviewed. A
      total of 128 consecutive ICSI/MESA cycles and a total of 120 consecutive
      ICSI/TESE cycles were performed up to December 1994. The two-pronuclei
      fertilization rate per intact oocyte (observed after the injection) was 58% and
      60%, respectively, when epididymal and testicular spermatozoa were used. The
      embryo transfer rate was similar for the two procedures (91% after ICSI/MESA and
      90% after ICSI/TESE). Fifty women became pregnant (positive HCG) when epididymal
      spermatozoa were used (39% per cycle and 40% per embryo transfer). These results
      are comparable to those obtained when ejaculated spermatozoa are used.

PMID- 9017100
TI  - Andrological work-up of patients undergoing microsurgical epididymal sperm
      aspiration or testicular sperm extraction.
AB  - Microsurgical epididymal sperm aspiration (MESA) and testicular sperm extraction
      (TESE) require close cooperation between andrologists, urologists and
      gynaecologists. Intracytoplasmic sperm injections were established in Giessen in
      March 1994 and embryo transfer (ET) was performed in 342 of 375 patients (91.2%).
      The percentage of pregnancies and ongoing pregnancies are 35.4% per ET (32.3% per
      cycle) and 25.1% per ET (22.9% per cycle), respectively. Microsurgical procedures
      such as epididymovasostomy or vasovasostomy and cryopreservation of human semen
      are also established methods. The purpose of the present study was to describe
      the andrological work-up for patients before MESA and TESE. Experiments
      demonstrate that incubation of testicular tissue samples in IVF medium and
      treatment with 1 mg ml-1 pentoxifylline increase the number of extracted motile
      spermatozoa. Centrifugation of the medium results in a further concentration of
      sperm cells. If no motile spermatozoa can be found in the supernatant medium,
      they may be extracted directly from the testicular tissue samples by means of a
      micromanipulator.

PMID- 9017101
TI  - Assisted reproductive technology in the management of azoospermic men--the
      Austrian experience.
AB  - Experience with intracytoplasmic injection of epididymal (MESA) and testicular
      spermatozoa (TESE) in Austria is summarized. Data from recent publications in
      scientific journals and results presented at different meetings were stratified
      for male factors, sperm retrieval methods, assisted reproductive techniques and
      conceptions. Four cooperative groups of andrologists and gynaecologists reported
      on MESA and TESE in Austria. They achieved five deliveries (one twin) and two
      ongoing pregnancies in 40 couples.

PMID- 9017102
TI  - Intracytoplasmic sperm injection (ICSI) with testicular sperm extraction (TESE)
      in non-obstructive azoospermia--two case reports.
AB  - Intracytoplasmic sperm injection (ICSI) with microsurgical epididymal sperm
      extraction (MESA) or testicular sperm extraction (TESE) can be offered to
      azoospermic men. We report our initial experience of two cases with ICSI-TESE in
      non-obstructive azoospermia. Both couples had a successful ICSI with embryo
      transfer. An ongoing triplet pregnancy at 21 weeks is observed.

PMID- 9017103
TI  - MESA and TESE: experiences of the German section of urological microsurgery.
AB  - The introduction of microsurgical epididymal sperm aspiration (MESA) and
      testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection
      (ICSI) has enlarged the therapeutic options for irreparable azoospermia. After
      standardization of the indications and surgical procedure, the German section for
      urological microsurgery combined the data of all groups performing assisted
      reproduction. The indication for MESA or TESE is given in cases of congenital
      aplasia of the vas deferens, irreparable obstruction of the reproductive tract,
      failure after refertilization, in combination with tubulovasostomy for subsequent
      cryopreservation and for conservatively untreatable ejaculatory disturbances.
      Until October 1995, 87 couples were treated by MESA and conventional IVF; the
      embryo transfer rate (ET) was 4.6%, the pregnancy rate 1.1%. One child (1.1%) was
      born. 179 couples were treated by MESA and ICSI, the ET was 68.2%, the pregnancy
      rate 18.4%, and 11 children (6.1%) were born. TESE in combination with ICSI was
      performed in 65 cases, the ET was 84.6%, the pregnancy rate 23.1% and 6 children
      (9.2%) were born. Modern technological developments in reproductive medicine and
      increasing experience in andrological surgery have stabilized the position of
      interdisciplinary therapeutic concepts for the treatment of infertile couples.

PMID- 9017104
TI  - Prospects for human reproductive medicine--applications of experimental
      techniques used in farm animal breeding.
AB  - Can assisted reproduction techniques performed in farm animal breeding be
      considered as future methods in human sterility treatment? The answer is no
      because, at the moment, the goals in human and animal reproduction are totally
      different. The methods that scientists are using or developing for farm animals
      are either without any therapeutic value for humans or they are forbidden by the
      German Embryo Protection Law. However, there are a few aspects which might be of
      value in the future of human assisted reproduction. The technique of in vitro
      maturation of immature follicles and oocytes, which is prerequisite in animal in
      vitro fertilization the female gamete pool after slaughter, might be used to
      obtain mature human oocytes from unstimulated cycles in women who do not respond
      to hormonal stimulation. Further more, it can be used in cancer patients to save
      their oocytes shortly before cancer treatment. Although still forbidden at the
      moment by the Embryo Protection Law, it is possible that the pre-implantation
      diagnosis of early embryos by the polymerase chain reaction technique after
      blastomere biopsy will become a valuable tool in preventing genome aberration in
      future.

PMID- 9017105
TI  - The current status of therapeutic HPV vaccine.
AB  - Cervical carcinoma is the second most common cause of cancer-related deaths in
      women worldwide. Recurrences occur in 15% of the patients after optimal treatment
      of low-risk early-stage disease. Treatment results of recurrent disease are
      relatively poor and for this reason new therapeutic strategies are warranted.
      Viral infection with human papillomavirus seems to have an essential part in the
      aetiology of cervical carcinoma. Evidence for the assumption that cervical
      carcinoma, among other malignancies such as melanomas, renal malignancies and
      Kaposi sarcoma, are immunogenic is provided by the fact that these malignancies
      grow more rapidly in the presence of systemic immunosuppression. Spontaneous
      regression for these tumour types is also described and immunohistochemical
      studies show extensive infiltrates in the tumour, consisting of immunocompetent
      cells. It is thus postulated that cellular immunity, and mainly the T-cell system
      plays an important role in the antitumour defence in cervical carcinoma. This
      review describes the rationale for the use of immunotherapy as treatment for
      cervical carcinoma as well as the results of recent developments in tumour
      immunology and its implications for the clinical use of immunotherapeutical
      approaches.

PMID- 9017106
TI  - Prophylactic colectomy in patients with hereditary nonpolyposis colorectal
      cancer.
AB  - Prophylactic colectomy is indicated in patients whose colons are at very high
      risk of developing cancer. Familial adenomatous polyposis (FAP) is the best
      example of a situation where prophylactic surgery is clearly necessary to prevent
      cancer, and has been shown to be effective in doing so. Recent advances in the
      molecular genetics of colorectal cancer have allowed presymptomatic diagnosis of
      patients with another dominantly inherited syndrome, hereditary nonpolyposis
      colorectal cancer (HNPCC). Prior to this, prophylactic colectomy had not been a
      consideration for patients in HNPCC families. A review of the outcome of
      colectomy and ileorectal anastomosis in FAP patients shows that although it is a
      major abdominal surgery there is a relatively low complication rate and the
      functional outcome is acceptable for a prophylactic procedure. The decision to
      apply colectomy to HNPCC patients depends on careful consideration of factors
      such as comorbidity, age, sphincter function, likely compliance with future
      surveillance and likely efficiency of colonoscopy as a cancer prevention
      strategy. In general, prophylactic colectomy is indicated in HNPCC gene carriers,
      because their lifetime risk for colorectal cancer is 80%.

PMID- 9017107
TI  - The role of laparoscopy in blunt abdominal trauma.
AB  - In a collective analysis of 11 reports with a total of 355 blunt abdominal trauma
      patients, the sensitivity and specificity of diagnostic laparoscopy in predicting
      the eventual need for therapeutic laparotomy were 94% and 98%, respectively, with
      an overall accuracy of 97%. Although fairly accurate and safe (morbidity rate
      about 1.2%), the invasiveness, cost and time-consuming nature of diagnostic
      laparoscopy limit its routine use in trauma patients. It could, however, be
      useful in selecting patients with minor or nonbleeding injuries for nonoperative
      management after positive peritoneal lavage or computed tomography, and in
      excluding occult bowel and diaphragmatic injuries in patients with equivocal
      findings, thereby reducing the number of unnecessary laparotomies. With the
      improvement of laparoscopic techniques and instrumentation, more injuries can
      probably be managed laparoscopically with all the benefits observed with the
      shift from open to laparoscopic procedures in other patient populations, and it
      is likely that laparoscopy will find its place as an integral part of evaluating
      and treating patients with blunt abdominal trauma. At present, however,
      laparoscopy cannot be recommended as a routine tool for evaluating patients with
      blunt abdominal trauma, except in controlled clinical trials.

PMID- 9017108
TI  - Gene transfer in haematological malignancy.
AB  - Although gene transfer was first suggested to treat inherited monogenic
      disorders, at present most clinical protocols are intended to treat patients with
      malignant disease. Although current vector technologies profoundly limit the
      potential therapeutic applications of gene transfer, the technique is already
      being successfully used to complement longer established therapies. This article
      reviews current and forthcoming applications of gene transfer to treat
      haematological malignancies.

PMID- 9017109
TI  - Ribozymes: structure, function, and potential therapy for dominant genetic
      disorders.
AB  - Some dominant genetic disorders, viral processes and neoplastic disorders base
      their pathogenicity on the production of protein or proteins that negatively
      affect cellular metabolism or environment. Thus, the inhibition of the synthesis
      of those proteins should prevent the biological damage. A promising approach to
      decreasing the level of the abnormal protein(s) is represented by specific
      interference with gene expression at the level of mRNA. The specific suppression
      of the expression of an mRNA can be achieved by using ribozymes. Ribozymes are
      RNA molecules able to break and form covalent bonds within a nucleic acid
      molecule. These molecules, with even greater potential advantages than antisense
      oligodeoxynucleotides, are able to bind specifically and cleave an mRNA
      substrate. There are advantages to using ribozymes instead of antisense
      oligodeoxynucleotides. Ribozymes can inactivate the target RNA without relying on
      the host cell's machinery and they have the capacity to cleave more than one copy
      of the target RNA by dissociating from the cleavage products and binding to
      another target molecule. Most of the studies performed to date have described the
      use of ribozymes as therapeutic agents for viral and cancer diseases. However,
      some dominant genetic disorders may also benefit from this approach. This is the
      case for some connective tissue disorders such as osteogenesis imperfecta, Marfan
      syndrome and the craniosynostotic syndromes.

PMID- 9017110
TI  - Towards genomic drug therapy with antisense oligonucleotides.
AB  - Antisense oligonucleotides represent a novel class of potential drugs for highly
      selective blocking of genes. The basic concept of antisense strategy is simple:
      an antisense molecule recognizes a complementary mRNA (or DNA) by sequence
      specific base pairing, and hence prevents translation (or transcription),
      resulting in a selective inhibition of protein synthesis. Because of these
      properties, antisense oligonucleotides have great potential as therapeutic agents
      in several human diseases, such as viral diseases, malignancies and dominant
      hereditary diseases. However, technical difficulties have slowed down their use
      as drugs: structural modifications are needed to increase the stability and
      potency of synthetic oligonucleotides, specific delivery systems are required to
      facilitate their entry into target cells, and more information is needed to their
      mechanism of action. Much of the current research on antisense oligonucleotides
      takes place at the interface of chemistry and biomedical sciences, a
      multidisciplinary field where finding a common language is sometimes difficult.
      The aim of this review is to present an overview of the antisense strategy in
      terms which should be understandable for chemists, biologists and physicians.

PMID- 9017111
TI  - The core symptoms of schizophrenia.
AB  - The diagnosis of schizophrenia is made on the basis of a diverse set of
      characteristic signs and symptoms. These include disturbances in perception and
      inference, abnormalities in communication, behaviour and motor activity, and
      deficits in emotional expressivity, hedonic capacity and drive. No single symptom
      or set of symptoms is pathognomonic, and the question of which symptoms are
      indeed at the 'core' of schizophrenia has been an issue of much debate, opinion
      and study since the disorder was first described a century ago. In this review,
      the symptoms emphasized in current diagnostic criteria for schizophrenia are
      described and the relative importance of these symptoms in the evolution of the
      schizophrenia construct is discussed.

PMID- 9017112
TI  - Abnormalities of brain structure and function in schizophrenia: implications for
      aetiology and pathophysiology.
AB  - In vivo imaging and post-mortem neuropathology studies have detected a variety of
      abnormalities in brain function and structure in patients with schizophrenia.
      Current models of the neural mechanisms involved focus primarily on frontal and
      medial temporal lobe structures and their interconnections, because deficits in
      these systems are relatively prominent against a background of generalized
      cerebral dysfunction, and because individuals with acquired lesions in these
      areas show many of the symptoms characteristic of schizophrenia. Family and twin
      studies have demonstrated similar abnormalities in some of the unaffected
      biological relatives of schizophrenics, indicating that some of these
      neuropathological changes are mediated in part by genetic predisposition to the
      disorder. Further, obstetric complications are associated with an increased risk
      for phenotypic schizophrenia and with greater severity of its neuropathological
      features in individuals at elevated genetic risk. These latter findings, combined
      with evidence of heterotopic displacement of neurones in temporolimbic and
      frontal regions and evidence that cognitive dysfunction during childhood precedes
      schizophrenia, imply that at least some of these brain abnormalities are neuro
      developmental in origin. The view emerging from this work is that schizophrenia
      is a brain disease the neuropathological features of which result at least in
      part from the unique and interacting influences of genetic factors and adverse
      obstetric events in utero.

PMID- 9017113
TI  - The molecular genetics of schizophrenia.
AB  - Until recently, schizophrenia has proven refractory to molecular genetic
      investigation, with all advances being hastily followed by retreat. However, more
      realistic interpretations of old study designs, combined with newer forms of
      investigation appear at last to be generating reproducible data, suggesting that
      the field is finally making sustained progress. In this review, we discuss the
      rationale behind the approaches now in widest application and discuss the results
      of recent linkage and association studies of schizophrenia. We conclude that,
      because of advances in the methodology of molecular genetics and improvements in
      study design, there are solid grounds for believing that susceptibility genes for
      schizophrenia will be identified in the foreseeable future.

PMID- 9017114
TI  - The neurodevelopmental theory of schizophrenia: evidence concerning structure and
      neuropsychology.
AB  - Severe schizophrenics as a group show subtle abnormalities of cerebral structure.
      Cerebral ventricular enlargement is the best replicated finding, and this tends
      to be associated with impairment of neuropsychological performance. The idea that
      these abnormalities have a neurodevelopmental origin gains indirect support from
      the, admittedly less consistent, evidence of abnormalities of cerebral asymmetry
      and of neuronal migration in adult schizophrenics, as well as from the better
      established behavioural, psychomotor, and cognitive impairments reported in
      preschizophrenic children. However, the relationship between childhood and adult
      neuropsychological and brain structural findings has not been proven, and we don
      not know whether only some schizophrenia has a developmental origin, or whether
      patients differ only in the degree of developmental impairment that they show.

PMID- 9017115
TI  - Dopamine in schizophrenia.
AB  - The DA hypothesis of schizophrenia is one of the oldest biological hypotheses of
      schizophrenia with many revised versions. However, it is unlikely that any single
      neurotransmitter hypothesis is able to explain the biological basis of such a
      highly heterogenous disorder as schizophrenia in a satisfactory way. Rather, it
      is evident that the biological vulnerability factors and the 'acute
      neurophysiology' of schizophrenic symptoms involve a complex set of imbalances of
      aberrant connections in neuronal circuits in the brain. Dopamine is likely to be
      one of the transmitter substances involved, as evidenced by recent neuroimaging
      studies in neuroleptic-naive schizophrenia. Regardless of whether the DA
      hypothesis of schizophrenia is true or not, the DA hypothesis of neuroleptic drug
      action still has a relatively solid basis. The DA D2 receptor blockade remains
      the best characterized clinically useful mechanism of drug action to alleviate
      psychotic symptoms. The ongoing and future work on the precise role of DA in
      schizophrenia should focus on first-episode/admission neuroleptic-naive
      schizophrenic patients. Such studies represent the best opportunity of finding
      out specific changes in the dopaminergic pathways and relating them in a
      meaningful way to various dimensions of psychopathology seen in schizophrenic
      patients.

PMID- 9017116
TI  - Expression of the BE-20 epididymal protein gene: in situ hybridization.
AB  - A protein designated as BE-20 was purified from cauda epididymal fluid of male
      rabbits and the amino acid sequence of the N-terminus was determined. A 23-mer
      oligonucleotide coding the N-terminal eight amino acids of the BE-20 protein was
      synthesized. The oligonucleotide was used as sense primer with rabbit epididymal
      mRNA as template in the RT-PCR system. The BE-20 cDNA consisted of 499 bp with an
      open reading frame of 285 bp encoding a deduced polypeptide composed of 95 amino
      acids. Digoxigenin-labeled BE-20 cDNA was prepared and used as a hybridization
      probe to detect the specific mRNA. The probe interacted with a 1.2-kb mRNA
      prepared from rabbit epididymis; mRNAs prepared from rabbit testis gave negative
      reaction. Using tissue sections, the BE-20 mRNA was located in the epithelial
      cells of the cauda epididymis and proximal segment of the ductus deferens by in
      situ hybridization method. Sections of the corpus and caput epididymis, testis,
      and liver gave negative reaction. Polyclonal anti-BE-20 antibodies were raised
      and found to inhibit in vitro the capacity of human sperm to penetrate zona-free
      hamster ova. The results suggest that BE-20 protein may influence maturation of
      spermatozoa during its movement through the epididymis and/or the capacity of
      sperm to fertilize ova.

PMID- 9017117
TI  - Viscosity of human seminal fluid: role of lysozyme.
AB  - The aim of this research was to evaluate the role of lysozyme in the phenomenon
      of seminal hyper-viscosity. The enzyme was determined in 142 samples of seminal
      plasma either leucospermic or not, with or without active macrophages classified
      according to their consistency (normal or high). The kinetic method with
      Micrococcus lysodeikticus as substrate was employed. No difference was found in
      enzymatic concentration expressed in nmol/L of enzymatic protein (mean +/- 2 SEM)
      on comparing normal and high seminal consistency groups, while differences proved
      highly significant in batches either leucospermic or not (n = 44, 197.2 +/- 51.3
      vs. n = 98, 108.3 +/- 12.8; p < .0005). On subdividing the normal and high
      consistency groups according to the count of polymorphonuclear leucocytes and the
      macrophagic responses, differences were also significant (p < .005 in both
      cases). Lysozyme concentration increases in presence of leucospermic reaction. In
      vitro lysozyme addition showed no significant effect on samples with high
      consistency. The results indicate that lysozyme plays no direct role in the
      phenomenon of seminal hyperviscosity, although its deficiency in cases of chronic
      infections may prove a factor aggravating the clinical picture.

PMID- 9017118
TI  - Effects of anordiol, an antiestrogen, on the reproductive organs of the male rat.
AB  - Anordiol, an antiestrogen, was administered at doses of 2.5 and 10 mg/kg day-1
      for 30 and 60 days to adult male rats. A significant decrease in serum LH, FSH,
      and testosterone levels occurred in the treated animals as compared to controls.
      Serum testosterone and LH levels decreased to about 15-35% of control value on
      day 15 of treatment and reached undetected levels thereafter. Serum FSH level
      also decreased to about 25-50% of control value by day 15 of treatment and
      remained at this level. Significant decrease in the weights of the tests and
      accessory reproductive organs occurred following anordiol treatment, while the
      body weights remained at pretreatment level. Histological examination of the
      tests revealed significant decrease in the diameter of the seminiferous tubules
      and in the number of germ cell elements. Spermatogenesis was arrested at the
      secondary spermatocyte stage. Leydig cells appeared atrophic and contained
      pyknotic nuclei. The epididymis, prostate, and seminal vesicle showed
      degenerative changes. The secretory activity of the glandular epithelium of the
      prostate gland appeared to be markedly reduced. In conclusion, anordiol acts by
      blocking gonadotropin production and/or release by the pituitary; thereby
      testosterone production by Leydig cells is not stimulated, causing
      spermatogenesis arrest.

PMID- 9017119
TI  - Luteinizing hormone pulsatility is altered in essential hypertension.
AB  - The aim of this investigation was to study the pattern of luteinizing hormone
      (LH) secretion in men with mild and moderate hypertension. LH pulsatility was
      evaluated for 8 h in 14 male patients, subdivided into 2 groups; group A,
      consisting of 8 patients, whose systolic blood pressure ranged between 180 and
      160 mm Hg and whose diastolic blood pressure was between 115 and 105 mm Hg; and
      group B, 6 patients whose systolic blood pressure ranged between 220 and 180 mm
      Hg and whose diastolic blood pressure was between 104 and 95 mm Hg. Seven healthy
      males were evaluated as controls (group C). The major changes of LH pulsatility
      in group A included an increased peak width, increased peak amplitude, and
      increased peak area. In group B the changes followed the same pattern as in group
      A, but were more pronounced. The number of LH peaks was reduced, the peak width
      was increased, and both peak amplitude and peak area were increased as compared
      to the control group. The pattern of LH pulsatility is altered in essential
      hypertension and the main feature is represented by the prolonged duration of LH
      peaks and their greater amplitude. The altered pattern of LH secretion is likely
      to reflect a primary hypothalamic derangement with the gonadotropin releasing
      hormone (Gn-RH) secreting neurons remaining synchronized for longer times and
      secreting larger Gn-RH masses than in normal subjects. Since the nuclei of the
      brain stem (A1-A6) involved in the control of Gn-RH secretion respond to blood
      pressure changes, the altered activity of monoaminergic neurons may be the link
      between hypertension and changes of LH pulsatility.

PMID- 9017120
TI  - Fibrinogen-like substance and thrombin-like enzyme in seminal plasma: coagulation
      system of human semen.
AB  - This investigation was conducted to examine the presence of fibrinogen-like
      substance and thrombin-like enzyme in human semen (human seminal plasma) after
      liquefaction. The human seminal plasma contained small amounts of respective
      substances which are absorbed on anti-fibrinogen and anti-thrombin III affinity
      columns, respectively. The thrombin-like enzyme with Gly-Pro-Arg-pNA amidolytic
      activity was inhibited by human seminal plasma trypsin-like enzyme inhibitor (HSP
      TI) and antithrombin III. The fibrinogen-like substance reacted with the thrombin
      like enzyme, forming a fibrin-like substance. It would appear that certain
      aspects of the coagulation process in human semen constitute the same process as
      the final stage of the blood coagulation system.

PMID- 9017121
TI  - inheritance of sperm centrioles and centrosomes in bovine embryos.
AB  - Immature cumulus oocyte complexes (COCs) were aspirated from ovarian follicles of
      slaughtered cow and matured for 24 h in TCM 199 medium with hormones. Eighty-five
      percent of oocytes matured with subsequent abstriction of the polar body. Matured
      COCs were then inseminated with frozen-thawed semen (2 x 10(6)/mL final
      concentration). Eighteen hours after insemination, fertilized COCs were vortexed,
      washed, and cultured to the pronuclear stage and syngamy (24-36 h
      postinsemination) and fixed for TEM. Unfixed embryos achieved a cleavage rate of
      54%, with 29% developing to blastocysts. Fertilization was confirmed by TEM.
      Examination of fertilized bipronuclear ova revealed the presence of a sperm aster
      associated with sperm midpieces, tails, and male pronuclei in several embryos.
      Further examination of embryos at syngamy showed centrioles at one pole of the
      first mitotic bipolar spindle in two embryos. Since the mature oocyte at
      metaphase II has no centrioles at spindly poles, this centriole was most likely
      derived from the sperm, which has a single proximal centriole associated with
      pericentriolar material in its neck region, like most mammalian sperm.
      Tripronuclear ova produced disorganized bipolar spindles or, rarely, tripolar
      spindles. Bovine embryos, too, follow Boveri's rule of paternal inheritance as in
      man and most animals. It is possible that both paternal centrosomes (centrioles)
      and maternal centrosomes are involved in the organization of bipolar spindles in
      these embryos, quite unlike the mouse embryo where maternal centrosomes seem to
      organize the first mitotic spindle. The bovine embryo appears to be an
      appropriate model to study centriolar inheritance.

PMID- 9017122
TI  - Effect of peritoneal fluid on sperm motility parameters in women with
      endometriosis.
AB  - To clarify the effect of peritoneal fluids (PF) of women with various stages of
      endometriosis on sperm motility, we utilized computer-aides sperm analysis (CASA)
      to analyze sperm movement characteristics. PF was collected in the early
      follicular phase (days 4-8) of the menstrual cycle from 48 women undergoing
      diagnostic laparoscopy. Only sperm samples having normal sperm parameters were
      chosen for study. Swim-up separation was performed for 1 h at 37 degrees C. Sperm
      suspension was mixed at a ratio of 1:1 with each of the following four groups:
      group 1, human tubal fluid (HTF) with 10% fetal bovine serum (control), group 2,
      normal PF (n = 16); group 3, minimal or mild endometriosis PF (n = 16); and group
      4, moderate or severe endometriosis PF (n = 16). The mixtures were analyzed at 0,
      1, 3, 6, and 24 h of co-incubation using the CASA system. At the end of the 24 h
      incubation, Supravital staining of sperm was done to check the viability of sperm
      in each group. Only time (F = 126.6, p < .001) has a significant effect on sperm
      motion parameters. At 6 h, sperm velocity (mean curvilinear velocity and mean
      straight line velocity) of the PF groups was significantly greater than that of
      the control, but there was no significant difference between each PF group. At 24
      h, the PF groups maintained 50% of initial sperm viability, compared with 13% of
      initial viability in the control group (p < .001). There was no adverse effect of
      PF in patients with endometriosis on sperm motion parameters.

PMID- 9017123
TI  - Induction of acrosome reaction in human sperm by exposing to an electrical field.

PMID- 9017124
TI  - Effect of sperm viability, plasmalemma integrity, and capacitation on patterns of
      expression of mannose-binding sites on human sperm.
AB  - The objective of this study was to characterize patterns of surface expression of
      mannose-binding sites (MBS) on human spermatozoa while evaluating the influence
      of sperm viability, plasma membrane integrity, and capacitation, D-Mannose
      binding sites were visualized by fluorescence microscopy using fluoresceinated
      mannose-enriched bovine serum albumin (FITC-DMA). To verify the probe
      specificity, 200 mM D-mannose and D-mannosylated albumin 200 micrograms/mL (DMA)
      were used as competitive inhibitors. Fluoresceinated bovine serum albumin (FITC
      BSA) was used as control. Sperm membrane integrity was checked with a hypoosmotic
      swelling test (HOST) and sperm viability with Hoechst 33,258 at 1 microgram/mL.
      Viable spermatozoa with intact plasma membrane presented two main patterns: light
      bar (weak labeling of the equatorial segment) and slot (labeling of the pre- and
      postequatorial areas with a negative band in between). These patterns were
      significantly inhibited when unlabeled D-mannose or DMA were included in the
      medium. The percentages of spermatozoa displaying these two patterns increases
      significantly during capacitation. Nonviable spermatozoa with altered plasma
      membrane integrity presented multiple fluorescent patterns, all of which were
      present when FITC-BSA was used as the marker. None of them could be suppressed by
      unlabeled D-mannose or DMA. Viable spermatozoa displayed two main patterns which
      increased their incidence with capacitation and may be the only specific patterns
      for surface MBS. Other patterns detected in spermatozoa bearing altered plasma
      membranes may be due to nonspecific BSA binding or intracellular MBS recognition.

PMID- 9017125
TI  - Characterization of a delta 5-3 beta-hydroxy pathway of testosterone synthesis in
      the human spermatozoa.
AB  - Sonicated specimens of freshly ejaculated sperm from two groups of husbands (n =
      6, age 32-38 years; n = 7, age 27-38 years) of infertile couples in the range of
      sperm concentration between 237.5 and 568.5; 131.1 and 256.7 millions per
      ejaculate were separately incubated with [7n-3H]pregnenolone and [1,2,6,7(
      3)H]dehydroepiandrosterone. Using the reverse-isotope dilution technique
      [3H]dehydroepiandrosterone and [3H]testosterone formed from the respective
      substrates were isolated and characterized, yielding 1.2 x 10(-2) to 4.6 x 10(
      20/0) and 7.1 x 10(-2) to 2.5 x 10(-10/0)/ Such metabolites were not evident in
      the controls. These results provide evidence for metabolic transformation of
      pregnenolone to testosterone via the delta 5-3 beta-hydroxy route.

PMID- 9017126
TI  - Effects of thyroid status on pituitary gonadotropin and testicular reserve in
      men.
AB  - This investigation was conducted to evaluate the effect of thyroid dysfunction on
      the pituitary-gonadal axis. Ten men with Graves' disease and 5 hypothyroid
      patients were studied; 10 normal males were studied as a control group. In
      untreated conditions hyperthyroidism was associated with a normal serum-free
      testosterone concentration, an increased serum of 17OHP levels, a reduced
      testosterone response to hCG stimulation, and a hyperresponse of LH to GnRH.
      These abnormalities reverted after normalization of high FT4 serum levels.
      Untreated hypothyroid men showed a normal hormone sex response to hCG, but the LH
      responst to GnRH was reduced, with a tendency to improve after T4
      supplementation. There was a strong and significant negative correlation between
      FT4 and testosterone response, expressed as an area under the curve, and a
      positive correlation with LH response to GnRH. Despite normal basal free
      testosterone concentrations, 70% of hyperthyroid and 60% of hypothyroid patients
      had complaints of decreased libido. The results suggest that thyroid hormones
      play an important dual pituitary-gonadal effect that is reflected by an
      impairment of testicular testosterone synthesis associated to hyperresponse to LH
      in hyperthyroidism and a defective LH response to GnRH in hypothyroidism.

PMID- 9017127
TI  - Hollow and fenestrated penile prosthesis: a new implant for treatment of
      impotence.
AB  - Penile implants are used for erectile dysfunction (ED). Their main disadvantage
      is that the cavernous tissue is destroyed and replaced by fibrous so that implant
      replacement is difficult and the penis loses its erectile function permanently.
      This paper describes a novel prosthesis which is hollow and fenestrated to
      preserve, as much as possible, the cavernous tissue. The fenestrated implant was
      used in 18 men with ED, while the solid Small-Carrion implants were used in 14
      impotent men who matched the 18 men in age and cause of impotence and acted as
      controls. Routine erectile function tests suggested that the ED was neurogenic.
      The fenestrated prosthesis was a hollow semisolid silicone rod with multiple
      openings (2-3 mm in diameter) along its whole length. The mean follow up of the
      patients was 43 +/- 12 SD months. No complications were encountered. Vaginal
      penetration was successful in the fenestrated and Small-Carrion implant groups. A
      total of 14/18 patients of the fenestrated prosthesis group experienced
      spontaneous erections upon sexual arousal, while none of the Small-Carrion
      prosthesis group did. During the sexual act the penis became tumescent in the
      patients of the former group but not in those of the latter. It is suggested that
      the residual cavernous tissue after insertion of the hollow fenestrated implant
      regenerates through the fenestrae into the implant lumen. This might explain the
      spontaneous erections upon sexual arousal and the tumescence during the sexual
      act, but this hypothesis remains to be proved histologically.

PMID- 9017128
TI  - Cytokines and their effects on maturation, differentiation and migration of
      dendritic cells.
AB  - In this review the role of cytokines in the maturation and migration of
      phenotypically and functionally diverse dendritic cell (DC) subpopulations is
      discussed and their role in progress of differentiation from bone marrow
      progenitors to lymphoid DC is described. GM-CSF is the most important cytokine
      for the development of functional DC and acts in concert with a varying mixture
      of other cytokines such as IL-4, IL-1 and TNF-alpha to direct the development of
      individual DC subpopulations.

PMID- 9017129
TI  - IL-7 mRNA is not overexpressed in mycosis fungoides and pleomorphic T-cell
      lymphoma and is likely to be an autocrine growth factor in vivo.
AB  - Interleukin-7 (IL-7) is thought to be a growth factor for cutaneous T-cell
      lymphoma (CTCL) since it has been shown that IL-7 transgenic mice develop a
      cutaneous disorder characterized by enhanced T-cell proliferation with
      progression to malignancy and that in vitro growth of Sezary cell lines is IL-7
      dependent. However, no direct in vivo evidence exists for the involvement of IL-7
      in the pathogenesis of CTCL. Therefore, we examined IL-7 mRNA expression in skin
      biopsies from patients with mycosis fungoides (MF) (n = 20) and pleomorphic T
      cell lymphoma (n = 5). By semiquantitative RT-PCR, IL-7 mRNA was not detectable
      in any of the CTCL samples, or in normal human skin (n = 8) or in skin from
      patients with psoriasis (n = 7) or atopic dermatitis (n = 5). In contrast, IL-7
      mRNA was detected in a biopsy from a kidney allograft transplant, in normal
      keratinocytes under various culture conditions and in several cell lines.
      Interestingly, using a highly sensitive nested PCR, IL-7 mRNA was detectable in
      all specimens tested, but there was no indication of IL-7 overexpression in MF
      then analysing lesions of patch, plaque or tumour stages. In contrast, increasing
      CD3 expression was found, which was most likely a consequence of the enhanced
      density of malignant T cells in advanced tumour stages. In summary, by the use of
      semiquantitative RT-PCR we were not able to detect IL-7 overexpression in MF or
      pleomorphic T-cell lymphoma. This indicates that IL-7 is probably not an
      autocrine growth factor in these CTCLs.

PMID- 9017130
TI  - The effect of IFN-gamma on healthy and psoriatic keratinocytes in a skin
      equivalent model is influenced by the source of the keratinocytes and by their
      interactions with fibroblasts.
AB  - We investigated the effect of interferon-gamma (IFN-gamma) on skin equivalents.
      Keratinocytes from involved and uninvolved skin from psoriatic subjects and from
      healthy subjects were grown on preproduced dermal equivalents (DE) containing
      fibroblasts from healthy skin or psoriatic lesions. Healthy keratinocytes were
      added when the dermal equivalents were either 22 days (DE(22)) or 37 days old
      (DE(37)) and psoriatic keratinocytes when the dermal equivalents were 28-52 days
      old (DE(28-52)). The skin equivalents were cultured for 11 days in a serum-free
      medium, and then with or without 500 U/ml IFN-gamma for 6 days. The expression of
      markers associated with differentiation and proliferation were investigated by
      immunohistochemistry. Differentiation was assessed by computed scores for the
      expression of cytokeratin 16, involucrin, filaggrin and the receptor for
      epidermal growth factor. The differentiating effect of IFN-gamma on healthy
      keratinocytes grown on DE(37) was significantly stronger than on psoriatic
      keratinocytes grown on DE(28-52). In healthy keratinocytes, the differentiating
      effect of IFN-gamma was significantly stronger in skin equivalents containing
      DE(37) than in those containing DE(22). The proliferation rate, i.e. the
      percentage of Ki-67+ keratinocytes in the basal layer, was studied in healthy
      keratinocytes grown on DE(22). In these cultures IFN-gamma increased the
      proliferation rate in the presence of psoriatic fibroblasts but not in the
      presence of healthy fibroblasts. HLA-DR expression was induced only in healthy
      keratinocytes grown on DE(22). We conclude that the influence of IFN-gamma
      epidermal differentiation and proliferation is influenced by the origins of both
      the keratinocytes and the fibroblasts. These findings suggest that interactions
      between keratinocytes and fibroblasts might be involved in the pathogenesis of
      psoriasis.

PMID- 9017131
TI  - Human HMC-1 mast cells exclusively express the Fc gamma RII subtype of IgG
      receptor.
AB  - Because of their localization at the interface of the internal and external
      environment mast cells play a crucial role in the immune response and in
      inflammatory reactions. Effects may be mediated not only by the high-affinity IgE
      receptor, but also by IgG receptors. Since in rodent mast cells signal
      transduction via the Fc gamma receptor family has been shown, we analysed the
      expression of surface receptors for IgG on the human mast cell line HMC-1. It was
      shown by flow cytometric analysis that HMC-1 constitutively expressed the Fc
      gamma RII/CD32 subtype whereas Fc gamma RI/CD64 and Fc gamma RIII/CD16 were not
      expressed. This exclusive expression of the Fc gamma RII subtype of IgG receptor
      is similar to the expression pattern of basophils, although concerning cell
      surface molecules HMC-1 rather seem to resemble monocytes. In contrast to
      monocytes the expression profile on HMC-1 did not change upon stimulation with IL
      4, TNF alpha, IFN gamma, PMA or salbutamol. Moreover, the mast cell-activating
      cytokine SCF and the calcium ionophore A23187 did not modulate the Fc gamma R
      profile in this study. To assess the importance of the exclusive Fc gamma RIII
      expression on HMC-1, we investigated whether the production of the cytokine TNF
      alpha is modulated via Fc gamma RII activation or if an increase in intracellular
      calcium could be observed. No significant modulation of TNF alpha release or of
      intracellular free calcium after crosslinking of Fc gamma RII by heat-aggregated
      IgG or by a second antibody was observed. It remains to be clarified whether this
      low-affinity subtype for the IgG receptor is involved in antigen-dependent
      sensitization of human tissue mast cells resulting in secretion of
      immunoregulatory cytokines. This mechanism may be important for disease states
      associated with circulating or tissue-bound immune complexes.

PMID- 9017132
TI  - Cytokine mRNA expression in cutaneous warts: induction of interleukin-1 alpha.
AB  - The persistence of human papillomavirus at cutaneous sites may be due to impaired
      trafficking of immune effector cells to the epidermis. We investigated whether
      HPV infection modulates cytokine mRNA expression in skin, thereby influencing
      local immunity. The mRNA expression of tumour necrosis factor-alpha, interleukin
      1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-8,
      IL-10, IL-12, granulocyte macrophage colony-stimulating factor, transforming
      growth factor-beta, interferon-gamma and amphiregulin were assayed in cutaneous
      warts and normal skin by semiquantitative reverse transcriptase-polymerase chain
      reaction. The expression of the cytokines was heterogeneous in the specimens but,
      of the 12 mRNA species investigated, only IL-10 mRNA was significantly
      downregulated in warts compared with normal skin (P = 0.002). IL-1 alpha mRNA
      expression was significantly upregulated in common warts (P = 0.019) and plantar
      warts (P = 0.003) compared with normal skin. The expression of IL-1 alpha and IL
      1ra mRNAs were significantly correlated in plantar warts (P < 0.05). Warts
      expressing IL-1 alpha also expressed amphiregulin, and there was a significant
      correlation between the expression of these two genes (P < 0.05). It is possible
      that IL-1 alpha expression in cutaneous warts may modulate the growth of
      papillomavirus-infected keratinocytes, mediated by amphiregulin, thus ensuring
      viral persistence.

PMID- 9017133
TI  - Expression of PCNA is associated with the presence of HPV DNA in skin warts.
AB  - A series of 90 excised cutaneous warts (verrucae vulgaris) were studied for the
      presence of HPV (human papillomavirus) DNA using in situ hybridization (ISH) with
      biotinylated full genomic DNA probes of HPV types 1, 2, 3, and 4. The expression
      of PCNA (proliferating cell nuclear antigen) was examined using conventional
      immunohistochemistry. The aim was to test the hypothesis that HPV can reactivate
      PCNA, including in the host replication machinery. HPV DNA of the above types was
      detected in 60 of 90 verruca biopsies studied (66.7%): HPV 2 in 56 cases, HPV 1
      in 2 cases, and HPV 3 in 2 cases. PCNA was expressed in all samples except two.
      The signal distribution of HPV DNA markedly differed from that of PCNA
      expression. ISH revealed strong HPV DNA signals in both the granular and the
      upper spinous cell layers, the most intense signals being detected in the upper
      epidermis. On the other hand, nuclear PCNA staining was present in the majority
      of parabasal and basal cells. Although strong PCNA signals within the wart
      lesions were found in the areas where HPV DNA was present, the PCNA positivity
      was almost invariably localized in the differentiated cells of the spinous cell
      layers, just below the HPV DNA-expressing cells. At the margins of the lesions,
      PCNA expression was still strong but disappeared abruptly towards the normal
      epidermis. HPV DNA-positive warts showed more intense expression of PCNA than did
      the HPV DNA-negative ones in this study. Our results indicate that PCNA induction
      is associated with the presence of HPV DNA, suggesting that HPV can reactivate
      PCNA, thus interfering with the host cell DNA replication machinery.

PMID- 9017134
TI  - Failure to demonstrate human papillomavirus (HPV) involvement in Bowen's disease
      of the skin.
AB  - To assess the role of human papillomavirus (HPV) in the aetiology of extragenital
      Bowen's disease (EBD), a series of 91 cases were analysed using in situ
      hybridization (ISH) with whole genomic DNA probes of HPV types 1, 2, 4, 6, 7, 11,
      12, 15, 16, 18, 26, 36, 37, 39, 42, 55 and 59. No HPV DNA was found in any of the
      samples tested. A polymerase chain reaction (PCR) was also used to analyse 37 of
      the 91 samples, using both the consensus primers MY09/MY11 which amplify a large
      number of HPV types from the L1 region and the degenerate primers CP65/CP70,
      which amplify the complete set of epidermodysplasia verruciformis (EV) HPV types.
      All the cases were also negative in the PCR. The results suggest that EBD is not
      HPV-related, at least in immunocompetent patients.

PMID- 9017135
TI  - Influence of UVA and UVB irradiation on hepatic and cutaneous P450 isoenzymes.
AB  - The influence of UVA and UVB irradiation of the skin for 1, 2 and 4 weeks on the
      activities of the hepatic and cutaneous P450 isoenzymes was investigated in
      female Wistar rats before and after systemic administration of hexachlorobenzene
      (HCB), a well-known porphyrogenic agent, which additionally induces P450 1A1 and
      P450 1A2 isoenzymes. UVA and UVB irradiation of the skin of controls and HCB
      treated animals did not influence porphyrin metabolism. In the nonporphyric rats
      hepatic EROD (P450 1A1) activity was induced by UVB, but the activity of ADM
      (P450 2B) and EMDM (P450 3A) was either minimally or not affected. In the HCB
      treated (porphyric) rats UVA and UVB irradiation resulted in a significant
      depression of HCB-induced EROD in the liver and in the skin. In both the
      nonporphyric and the porphyric rats UVA and UVB irradiation had no effect on
      hepatic ADM activity. In the liver of the nonporphyric animals EMDM activity
      remained unchanged after UVA and UVB irradiation, whereas in the HCB-treated
      animals the activity of this enzyme was increased. Finally, after UVA and UVB
      irradiation cutaneous EMDM activity was increased in the controls, whereas the
      HCB-induced increase of this enzyme in porphyric animals was decreased. In
      addition long-term (28 days) UVB irradiation decreased hepatic GSH content
      significantly in normal and porphyric rats. These experimental findings cannot be
      directly extrapolated to humans; however, they suggest that exposure of human
      skin to UV radiation may result in alterations in the activity of cutaneous
      hepatic and other extracutaneous P450 isoenzymes.

PMID- 9017136
TI  - Differential apoptotic pattern induced by photodynamic therapy and cisplatin in
      human squamous cell carcinoma cell line.

PMID- 9017137
TI  - UVB irradiation induces decreased expression of beta 2-adrenergic receptors in
      cultured keratinocytes.

PMID- 9017139
TI  - Absence of picornavirus genome in pityriasis rosea.

PMID- 9017138
TI  - Beneficial clinical effects of cyclosporin A on severe psoriasis and its
      dissociation from serum concentration of soluble interleukin-2 receptor, soluble
      interleukin-6 receptor, soluble CD14 antigen, soluble intercellular adhesion
      molecule-1, and soluble vascular cell adhesion molecule-1.

PMID- 9017140
TI  - Type XII collagen in human skin: studies on its localization with monoclonal
      antibodies.

PMID- 9017141
TI  - Present status of classification of viruses of vertebrates.
AB  - The VIth Report of the International Committee on Taxonomy of Viruses (ICTV) was
      published in 1995. We have briefly characterized its contents and discussed the
      most important changes that have been made in the classification of viruses of
      vertebrates. The present line up of families and genera of viruses of
      vertebrates, and subviral agents and unassigned viruses is also provided. We
      propose an allocation of families of viruses of vertebrates according to a
      conjectural evolutional connection between the type and class of genomic nucleic
      acid. Finally the directions and intentions of the ICTV have been reviewed from
      the Virology Division News in Archives of Virology (1994/1995). These will be
      considered in the VIIth Report of the ICTV scheduled for publication after the
      XIth International Congress of Virology in Sydney in 1999.

PMID- 9017142
TI  - Hepatotropic viruses seen by clinicians.
AB  - During last decades we have been witnessing substantial progress in hepatology,
      particularly in relation to viral hepatitis. Novel diagnostic tools allowed
      researchers to define new etiological agents, understand their epidemiology and
      pathogenesis as well as develop effective preventive measures. However, several
      important questions still remain to be answered and no satisfactory therapeutical
      agents for chronic hepatitis are available. Basic epidemiological, preventive and
      clinical aspects of viral hepatitis are being discussed in this paper.

PMID- 9017143
TI  - Cytomegalovirus and atherosclerosis.
AB  - The investigations reviewed in this paper provide evidence that a member of the
      herpesvirus family can cause atherosclerosis in chickens. In vitro experiments,
      as well as studies of arteries from infected birds, suggest that a virus-induced
      alteration of cellular metabolism, which results in the accumulation of
      cholesterol and cholesteryl esters, may be the primary mechanism in development
      of viral atherosclerosis. In addition, the fact that the same avian virus induces
      a malignant lymphoma suggests that it may also have the potential to stimulate
      the proliferation of other cells, notably arterial smooth muscle cells. The
      evidence for involvement of one or more members of the herpesvirus family in
      human atherosclerosis is much more circumstantial. Cytomegalovirus (CMV) is
      prevalent, increasing with age, so that a majority of the human population
      becomes infected by adulthood. As with other herpesviruses, the infection with
      CMV is usually subclinical or latent. Although the sites of latency for CMV have
      not been established, both smooth muscle and leukocytes are likely possibilities.
      The observations of viral antigens and nucleic sequences, but not infectious
      virus, in arterial smooth muscle cells suggests that latent CMV infection of the
      arterial wall may be common in patients with atherosclerosis.

PMID- 9017144
TI  - Characterization of rotaviral RNA isolated from children with gastroenteritis in
      Poland.
AB  - Rotaviruses were detected in 37% (331/895) of stool specimens collected from
      children with gastroenteritis attending three hospitals in Warsaw between January
      1981 and March 1994. An analysis of rotavirus electrophoretypes circulating in
      Warsaw and Cracow, Poland, over 6 years showed that all 176 electrophoretypes
      encountered were characteristic of group A rotaviruses. Based on variations in
      the migration pattern of RNA genome segments when passed through polyacrylamide
      gels, 10 different electrophoretypes were identified: 86% were long patterns and
      14% were short patterns. Mixed infections were observed in two cases.

PMID- 9017145
TI  - Content of beta-carotene in blood serum of human papillomavirus infected women
      with cervical dysplasias.
AB  - Studies were carried out in 528 women hospitalized in the Department of
      Obstetrics and Gynecology Medical Academy in Lublin. Besides the control group,
      patients were classified according to the observed histopathological changes in
      the cervix (CIN) and found infections with human papillomavirus (HPV). In all
      cases beta-carotene content in blood serum was examined. HPV infection was
      probably a cause of decrease of beta-carotene content. It was found that with
      increased advancement of cervical dysplasia the level of beta-carotene in serum
      decreased.

PMID- 9017146
TI  - Primary hepatocellular carcinoma in patients with chronic hepatitis B virus
      infection.
AB  - The paper presents 66 hepatocellular carcinoma (HCC) patients (57 males, 9
      females) with chronic hepatitis B virus (HBV) infection in the clinical,
      diagnostic and therapeutic aspects. In 60 cases, hepatic cirrhosis was the
      primary hepatic disease, in 5--chronic hepatitis, and in 1--neoplasm developed in
      morphologically normal liver. Forty out of 66 patients were HBsAg seropositive.
      In 96% of the cases, anti-HBc antibodies were detected. In 76% of the cases, the
      infection was subclinical. In all patients, neoplasm was diagnosed in the late,
      symptomatic stage of the disease. Okuda's classification was used to stage the
      disease. The following treatment methods were applied: surgical in 5 patients,
      embolization of hepatic artery with intra-arterial administration of cytostatics
      in 5, intravenous chemotherapy in 39, interferon alpha in lozenges in 15. In 44
      patients, an objective response to treatment (according to WHO criteria) was
      achieved: in 5 (I and II Okuda's stage)--a complete response (CR) for the period
      of 0.5-4 years, in 2 (III Okuda's stage)--partial response (PR) with prolonged
      survival time up to 1 year, in 21--no change (NC). The average survival time of
      non-treated and treated patients was, respectively: in the I Okuda's stage 2.05
      and 9.55 months, in stage II 1.36 and 7.36 months, in III stage 1.15 and 5.05
      months. The differences in the average values are statistically significant. Only
      combined therapy, including both surgical and devascularization methods, applied
      to HCC patients results in achieving a long-lasting complete remission of the
      disease. Interferon alpha oral therapy improves the effects of the treatment.

PMID- 9017147
TI  - Acquisition of susceptibility to vesicular stomatitis virus infection by murine
      resident peritoneal cells during culturing in vitro.
AB  - We have studied the effect of culturing in vitro of BALB/c--mouse resident
      peritoneal cells (RPC) on their ability to replicate vesicular stomatitis virus
      (VSV). Results of 36 experiments performed on RPC, freshly isolated from
      individual female mice, showed that over 70% of them expressed constitutive
      antiviral immunity against VSV infection. The virus multiplied to low titers (<
      or = 10(3) TCID50/10(6) cells) only in 10 out of 36 cases. After several days in
      culture, the RPC were found to lose the resistance and VSV multiplied in the
      cells to high titers (up to 10(7) TCID50/10(6) cells). The time period, required
      for the cultures to reach a full ability to replicate the virus, was individually
      differentiated and ranged from 24 h to over 96 h.

PMID- 9017148
TI  - Syphilis and AIDS.
AB  - Evidence is shown that syphilis has become a major public health problem again.
      From 1988 to 1995 the permanently growing number of new cases of syphilis in the
      world was observed. The majority of the syphilitic cases in the patients are
      difficult for curing. The central nervous system is often involved in early
      syphilis. Previously the neurosyphilis was very rare. The reason for development
      of this stage of syphilis, may be an inadequate treatment as well as a weakening
      of the immunological responses. The latter one very often is caused by additional
      non-symptomatic infection including human immunodeficiency virus (HIV).
      Syphilitic ulcers act as a portal of entry for HIV. Analysis of cases with double
      infection with Treponema pallidum and HIV indicate that HIV infection may
      accelerate the course of syphilis and the presence of syphilis may also have
      influence on progression of the chronic HIV infection to AIDS. Taking into
      account that HIV infection alters the response to the treatment also, one can
      suggest that all of the patients with syphilis should be examined for the
      presence of HIV infection.

PMID- 9017149
TI  - Does hepatitis B virus or hepatitis C virus infection influence CD4 count in HIV
      positive individuals?
AB  - Objective of the study was to determine whether there is any influence of
      hepatitis B virus (HBV) or hepatitis C virus (HCV) infection on CD4 count decline
      rate in HIV-infected individuals. Retrospective analysis of consecutive CD4
      counts was conducted in 72 HIV-infected untreated individuals (including 57
      intravenous drug addict (i.v.d.a.)) in relation to their serological markers of
      HBV and HCV infection and the history of i.v. substance abuse. Anti-HBc
      seropositive individuals had slower CD4 count decline rates compared to anti-HBc
      seronegative ones (-0.20%/month vs. -2.90%/month, Kruskal-Wallis H = 4.77, p =
      0.029). Anti-HCV serostatus had no influence on CD4 count decline rates (
      0.47%/month for anti-HCV seropositive persons vs. -0.61%/month for anti-HCV
      seronegative ones, p = 0.91). History of i.v. substance abuse did not affect the
      CD4 count decline rates too (-0.83 for i.v.d.a. vs +0.74 for non-i.v.d.a., p =
      0.26). In our study HIV-infected individuals seropositive for anti-HBc tended to
      have substantially lower CD4 count decline rates compared to seronegative ones.
      Neither anti-HCV serostatus nor the history of i.v. substance abuse influenced
      the CD4 count decline rate. This observation arises question about the possible
      nature (molecular?, immune-based?) of potential mutual interactions between HIV
      and HBV infections.

PMID- 9017150
TI  - Long-term assessment of interferon responses in the HIV+ and AIDS patients.
AB  - Impairment of interferon (IFN) system in human immunodeficiency virus (HIV)
      infection and acquired immunodeficiency syndrome (AIDS) became a basis for
      searching IFN responses to monitor the disease progression. For detailed
      investigations 16 HIV+/AIDS patients with at least 4 successively taken blood
      samples available for IFN determinations were selected. IFN responses were tested
      in two ways. Firstly, IFN level in plasma was measured. Secondly, capacity of IFN
      production by leukocytes was evaluated. The latter was determined in the whole
      blood assay, in which Newcastle disease virus (NDV) and phytohemagglutinin (PHA)
      were used as IFN-alpha and IFN-gamma inducers, respectively. The levels of IFN
      induced in whole blood leukocytes varied considerably in all individuals that had
      been tested. Nevertheless, two patterns of IFN responses were observed. In
      pattern I, patients had low levels of IFN in plasma and high levels of induced
      IFN-alpha and IFN-gamma. It was characteristic for 8 patients in good clinical
      condition. On the contrary, severe disease found in 2 patients was correlated
      with high levels of IFN in plasma and low levels of induced IFNs (pattern II). In
      6 patients IFN responses were classified as intermediate pattern I/II suggesting
      transition from pattern I to pattern II. A variation of pattern I was found in
      the case of a patient defined as long-term survivor having relatively low levels
      of all IFN tested. The results suggested that interferon measurements reflected
      clinical condition of HIV+ patients showing not only past but also current immune
      changes.

PMID- 9017151
TI  - Interferon and tumor necrosis factor production by peripheral blood leukocytes of
      patients with infectious mononucleosis.
AB  - Blood samples from 29 patients with infectious mononucleosis (IM) in phases of
      acute disease and convalescence were obtained. Interferon alpha (IFN-alpha) and
      tumor necrosis factor alpha (TNF-alpha) activity was detected in sera of patients
      both in: acute and convalescence phase, however when IFN titers were higher in
      the acute than convalescence phase, TNF titers were the highest in convalescence.
      In the whole blood assay Newcastle disease virus (NDV), phytohemagglutinin (PHA)
      and concanavalin A (ConA) and lipopolysaccharide (LPS) were used as cytokine
      inducers. A significant decrease in IFN titer induced in vitro with NDV, PHA and
      ConA was observed in blood leukocytes of patients in the acute IM phase. In
      convalescence the ability of blood leukocyte of IM patients to produce IFN
      returned to normal, comparable with control. However, blood leukocytes of IM
      patients in the acute phase produced more TNF in response to LPS than in
      convalescence. The role of the observed overproduction of TNF in the course of IM
      similar to that in HIV infection should be elucidated.

PMID- 9017152
TI  - Comparison of the long-term effects of treatment with oral and parenteral
      interferon alpha in chronic viral hepatitis patients.
AB  - This report presents the interferon alpha (IFN-alpha) treatment results for 75
      patients with chronic hepatitis B virus (HBV) (51 cases) and hepatitis C virus
      (HCV) (24 cases) induced hepatitis in maximal 61 months follow-up. Among the
      group of 51 patients with chronic HBV hepatitis, 35 were treated orally with IFN
      alpha in the form of lozenges in low daily doses (37.5-150 U). The treatment was
      completed in 32 cases. The remaining 16 patients with chronic HBV hepatitis
      completed the treatment with parenteral IFN-alpha (3 x 10(6) U, 3 times a week).
      Positive results measured by the use of seroconversion in the HBe-antigen system
      were obtained for 68.7% (5-61 months follow-up) and 56.2% (7-44 months follow-up)
      of the patients treated with oral and parenteral IFN-alpha, respectively. Among
      the group of 24 patients with chronic HCV hepatitis, the first 6 patients were
      initially treated with IFN-alpha in the form of lozenges, in low daily doses.
      Biochemical remission was not achieved in these patients; genotype 1b was
      documented in 4 of them. Both, the first 6 patients (after a break) and the
      remaining 18 were treated with IFN-alpha parenterally, as in HBV patients.
      Temporary clinical and biochemical remission was achieved in 62.5% of the cases
      during the treatment, however the durable remission observed during 6-29 months
      of follow-up was achieved in 20.4 of the cases only.

PMID- 9017153
TI  - Viral vaccines: selected topics.
AB  - Significant role of viruses in pathology, their dominating position in etiology
      of infectious diseases point at the special position of active prophylactic
      procedures based on vaccination. The real role and value of viral vaccines of
      classic and modern generations, the limitation of immune potency in suppression
      of defence mechanisms, some problems of immunization against virus vertical
      transmission are presented in the paper. The reader may find tables which
      cumulate selected but significant patterns of viral vaccines and vaccinations,
      and selected papers devoted to topics discussed.

PMID- 9017154
TI  - Controlling orthopoxvirus infections--200 years after Jenner's revolutionary
      immunization.
AB  - An 11-year global WHO campaign for eradication of smallpox finished in October
      1977 as the result of Edward Jenner's primary success in 1796, who for the first
      time applied human vaccination against variola virus (VARV). The 200th
      anniversary of this happening is a good occasion to summarize the current status
      of the knowledge about the role of B and T lymphocytes in the control of
      orthopoxvirus infections. This short review concentrates on general
      characteristics of orthopoxviruses and the immune response to infection, mainly
      by vaccinia virus (VV) and ectromelia virus (EV).

PMID- 9017155
TI  - Studies on the stability of HSV-1 temperature sensitive 28 degrees C clone.
AB  - The temperature mutants of herpes simplex virus type 1 has been received. The
      following properties on different levels of passages were investigated: stability
      of virulence, virus infection titer and immunogenicity. The virulence stability
      was expressed by percent of survivors and mean survival time in infected mice
      (CFW/Pzh and BALB/cPzh strains). Virus infection titer's stability was measured
      after prolonged exposure of temperature sensitive mutant (ts 28 degrees C) to
      critical temperatures (+4 degrees C and from +20 degrees C to +23 degrees C).
      Stability of immunogenic potency of ts 28 degrees C was evaluated in mice
      immunized with the virus on different level of passages and after that they were
      challenged with highly pathogenic temperature resistant clone (tr 39 degrees C).
      The performed experiments proved the stability of investigated features.

PMID- 9017156
TI  - Influenza: problem in Poland as elsewhere.
AB  - The present paper deals with the epidemiological and clinical properties of
      influenza, taking into consideration differences in the course of the disease its
      consequences, and infections in high-risk groups. Special attention was paid to
      problems connected with influenza prophylaxis, and especially to the problem of
      vaccination. The authors point out that if the vaccine contains recommended
      strains for a given season and if the vaccination is done in the proper time, the
      immunity obtained in this way is effective.

PMID- 9017157
TI  - Characteristic of humoral response of elderly to inactivated influenza vaccine.
AB  - Eighty persons immunized with inactivated influenza vaccine in 1990-1991 epidemic
      season were examined. Serological tests: hemagglutination inhibition (HI), lectin
      neuraminidase (LN) and Western blot were performed with serum specimens taken
      before and 3-4 weeks after vaccination. Distribution of anti-influenza antibodies
      in the subclass was also examined. The results revealed humoral response to
      vaccine strains of influenza virus and also to strains caused infections in the
      past.

PMID- 9017158
TI  - Phosprenyl: a novel drug with antiviral and immunomodulatory activity.
AB  - A novel antiviral drug with immunomodulatory activity (Phosprenyl) is presented.
      The main active ingredient of the preparation is polyprenyl phosphates. This
      medicine is highly efficient against a number of viruses, including HIV in vitro,
      and tick-borne encephalitis and rabies viruses in the experimental models in
      vivo. In veterinary practice Phosprenyl is now regarded as an effective
      therapeutic means for treatment of canine distemper, hepatitis, enteritis, etc.

PMID- 9017159
TI  - Retrograde transport of acidic fibroblast growth factor as a part of the growth
      factor signaling.
AB  - The plasma membrane represents an impermeable barrier to proteins and other
      macromolecules. However, certain exogenous proteins are able to cross cellular
      membranes and gain access to the cytosol. The best examples are bacterial and
      plant protein toxins, acting on intracellular targets. During last few years the
      number of known proteins possessing the capability to cross cellular membranes in
      the reverse direction and reach the nucleus has increased (acidic and basic
      fibroblast growth factor, interleukin 1, angiogenin, Schwannoma derived growth
      factor, homeoprotein Antennapedia, HIV-1 Tat protein are some examples). Here,
      the role of transport of exogenous acidic fibroblast growth factor to the nuclear
      location as a part of the growth factor signaling is discussed, and the current
      knowledge on this issue is reviewed.

PMID- 9017160
TI  - Immunomodulatory activity of conformationally restricted peptides related to TGF
      beta-2 90-99 sequence.
AB  - Continuing our research on the immunomodulatory activity of the peptides related
      to the proteins of TGF-beta family, we have synthesized and investigated by
      Jerne's plaque forming cell (PFC) test and delayed type hypersensitivity (DTH)
      test the following linear peptides and their cyclic (disulphide-bridged)
      analogues: Lys-Thr-Pro-Lys-Ile (Ia) and Cys-Lys-Thr-Pro-Lys-Ile-Cys (Ib), Tyr-Ile
      Gly-Lys-Thr-Pro (IIIa) and Cys-Tyr-Ile-Gly-Lys-Thr-Pro-Cys (IIIb), Tyr-Ile-Gly
      Lys-Thr-Pro-Lys-Ile (IVa) and Cys-Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Cys (IVb), Tyr
      Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Glu (Va) and Cys-Tyr-Tyr-Ile-Gly-Lys-Thr-Pro-Lys
      Ile-Glu-Cys (Vb). It has been found that the insertion of the sequence of Ia into
      the disulphide bridged Ib generates a product with enhanced immunosuppressive
      activity. The similar procedure applied to IIIa, IVa and Va produces cyclic
      peptides devoid of any activity or of a diminished activity in DTH test. The
      exchange of Pro residue of Ia D-Pro resulted in the analogue IIa with a preserved
      immunosuppressive activity. The disulphide-bridged peptide IIb, a cyclic analogue
      of IIa, exhibited the same activity as IIa in both: PFC and DTH tests.

PMID- 9017161
TI  - Colostrinine: a proline-rich polypeptide from ovine colostrum is a modest
      cytokine inducer in human leukocytes.
AB  - A proline-rich polypeptide (PRP), now named colostrinine, molecular weight
      18,000, was isolated from ovine colostrum and characterized by Janusz, Lisowski
      et al. The nonapeptide (NP) which is an active fragment of PRP was obtained by
      chemical synthesis. In mice, PRP has many regulatory effects on the humoral and
      cellular immune response. The present paper describes PRP as a cytokine inducer.
      PRP at concentration of 1-100 micrograms/ml was found to induce production of
      interferon (IFN) and tumor necrosis factor (TNF) in human peripheral blood
      leukocytes and in whole blood cultures. The effects were dose related. The
      identified till now cytokines induced by PRP were IFN-gamma and TNF-alpha but
      many other cytokines may be stimulated also. NP was considerably less active as
      the cytokine inducer than the natural PRP. Two volunteers given orally once daily
      for two to three weeks 100 or 200 micrograms PRP in tablets were found to develop
      the tolerance of IFN induction and had the modified TNF response. Furthermore,
      the PRP-treated volunteers showed signs of psycho-stimulation. Taken together our
      observations suggest that ovine PRP is active in humans and may have therapeutic
      value as an immunostimulant and/or neurotropic cytokine.

PMID- 9017162
TI  - Immunological status of patients subjected to cardiac surgery: serum levels of
      interleukin 6 and tumor necrosis factor alpha and the ability of peripheral blood
      mononuclear cells to proliferate and produce these cytokines in vitro.
AB  - The aim of this study was to monitor plasma interleukin 6 (IL-6) and tumor
      necrosis factor alpha (TNF-alpha) levels in patients subjected to cardiac surgery
      under general anesthesia. In addition, proliferation of peripheral blood
      mononuclear cells (PBMC) to phytohemagglutinin (PHA) and the ability of these
      cells to secrete lipopolysaccharide-induced IL-6 and TNF-alpha during the
      observation period was investigated. IL-6 and TNF-alpha levels were measured
      using bioassays. We found that despite high variability in the postoperative
      response of the patients, characteristic kinetics in the appearance of the
      cytokines in plasma could be demonstrated. Most significant phenomenon was an
      increase of IL-6 level 1 day after operation associated with an inhibition of TNF
      alpha concentration. Relatively high, preoperative concentrations of these
      cytokines were probably elicited by stress. Control, healthy donors, did not
      exhibit measurable levels of these cytokines. In terms of proliferative response
      of PBMC to PHA and of cytokine production in vitro, the patients could be
      classified into low and high responding. The proliferative response of PBMC from
      low responders was progressively increasing and the response of high responders
      did not exhibit meaningful changes throughout the observation period. PBMC from
      low producers of IL-6 showed also an increased ability to secrete this cytokine
      during the monitoring time while the cells from high producers yielded less IL-6
      on the last day of the follow up. Regarding TNF-alpha production, PBMC from low
      responders reacted strongly by secretion of this cytokine on day 1 after surgery
      in contrast to high responders whose cells yielded less TNF-alpha after surgery.
      In majority of cases TNF-alpha production had a tendency to diminish on the last
      day of observation. We conclude that the changes in cytokine levels as well as an
      altered reactivity of PBMC in vitro reflect the immune response to the
      postoperative trauma and are desirable for a normal course of the immune response
      and wound healing.

PMID- 9017163
TI  - Comparison of serological reactions of Rickettsiae-infected patients and rabbit
      anti-Proteus OX antibodies with Proteus OX2, OX19 and OXK lipopolysaccharides.
AB  - The reactivity of anti-Rickettsiae human antibodies with Proteus OX cells is used
      as a presumptive rickettsial diseases diagnostic test Weil-Felix reaction. In
      presented studies we compare the reactivity of human anti-Rickettsiae and rabbit
      anti-Proteus antibodies with series of Proteus OX2, OX19 and OXK
      lipopolysaccharides (LPS). Polyclonal rabbit anti-OX2, anti-OX19 and anti-OXK
      sera reacted only with the homologous LPS--OX2, OX19 and OXK, respectively. The
      antibodies of Japanese spotted fever patients were less specific and reacted with
      OX2 as well as OX19 LPS. The antibodies of scrub typhus patients recognized
      Proteus OXK LPS, only. The serological reactions of O-antigen of P. mirabilis
      S1959 indicated that this, previously serologically not classified, strain may
      belong to the OXK group. Bacteria, used in the studies, came from the American,
      Japanese and European strain collections. The series of OX2, OX19 and OXK LPS,
      isolated from these Proteus strains, presented pattern of electrophoretic
      mobility and serological reactivities specific for each of OX-group types.

PMID- 9017164
TI  - Alterations of Tamm-Horsfall protein immunoreactivity after partial desialylation
      and deglycosylation.
AB  - The role of the carbohydrate moiety of Tamm-Horsfall protein (THP) was
      investigated by studying the effect of partial enzymatic desialylation and
      deglycosylation on its immunoreactivity. In our experiments primarily sialic acid
      alpha 2,6 linked to a galactose was split off, resulting in a 14% increase of
      immunoreactivity. It was increased up to 21% by further removal of the sugar
      residues. We also found that complexes composed of THP and human serum albumin,
      immunoglobulin G or transferrin reacted with anti-THP antibodies. When these
      complexes were formed with desialylated or deglycosylated THP an essential
      increase of this reactivity (about 25%) occurred. Our studies indicate that
      modifications of the carbohydrate moiety of THP (which might occur in vivo by
      changes in the glycosylation process e.g. in pathologic conditions) lead to
      increased exposure of THP to the immune system.

PMID- 9017165
TI  - Selective spectrophotometric determination of glucose and fructose in the
      presence of aldoses using phenol-acetone reagent and cerium(III) chloride.
AB  - Aqueous mixtures of glucose and fructose produce red solutions when treated with
      2% (w/v) phenol in 5% (v/v) aqueous acetone in the presence of concentrated
      sulfuric acid. The color is stable for days, and the red chromophore has an
      absorbance maximum at 568 nm. When the concentration of phenol is raised to 25%,
      fructose, but not glucose, produces red solutions, allowing for the selective
      detection of ketoses. Two complementary methods have been developed to remove the
      interference of ketoses in solutions containing glucose. The first one relies on
      the selective reduction of ketoses with sodium borohydride in the presence of
      cerium(III) chloride prior to the addition of the phenol-acetone reagents. The
      second method is based on the differential specific determination of glucose
      using 2% versus 25% levels of phenol. The relative sensitivities of different
      sugars are also presented as well as the applicability of the methods using
      bacterial polysaccharides for immunochemical analyses. The quantitative
      determination of glucose or ketoses in the polysaccharides does not require
      hydrolysis prior to the estimation.

PMID- 9017166
TI  - Treatment of drug-induced agranulocytosis with colony stimulating factors (G-CSF
      or GM-CSF).
AB  - The application of granulocyte-macrophage and granulocyte colony stimulation
      factors (GM-CSF and G-CSF) has been progressively increased in the treatment of
      patients with agranulocytosis. The aim of our study was to compare the time of
      neutrophil recovery in patients with severe agranulocytosis treated with G-CSF or
      GM-CSF and the historical control group. We have studied 6 patients with
      agranulocytosis treated with stimulating factors and 7 patients in historical
      control group. Most of the patients have been exposed to thiamazole or non
      steroid antiinflammatory drugs. Our results demonstrate that patients receiving
      colony stimulating factor have a significantly shorter period of recovery (the
      mean time 8.7 +/- 1.98 days) than the historical control group (the mean time
      11.0 +/- 2.24 days). We observed also a shorter time of antibiotico-therapy and
      hospitalization in the group of patients treated with colony stimulating factor.

PMID- 9017167
TI  - Interaction of 2-chlorodeoxyadenosine in combination either with interferons or
      recombinant human tumor necrosis factor alpha on myeloid progenitor cells in
      vitro.
AB  - The objective of the present study was to investigate the interactions of 2
      chlorodeoxyadenosine (2-CdA) with interferon alpha or gamma (IFN-alpha, IFN
      gamma), as well as between 2-CdA and recombinant human tumor necrosis factor
      alpha (rhTNF-alpha), on the clonal growth of granulocyte-macrophage progenitor
      cells (CFU-GM) from patients with chronic myeloid leukemia (CML) and on
      clonogenic leukemia blasts (CFU-L) from acute myeloid leukemia (AML) patients.
      Progenitor cell culture in semisolid medium in vitro was applied and the
      percentage of colony growth inhibition was evaluated. The use of 2-CdA either
      with IFN-alpha or IFN-gamma and 2-CdA with TNF-alpha was found to inhibit, in a
      dose dependent manner, the growth of colonies formed by hematopoietic precursor
      cells from CML and AML patients as well as from normal individuals, with the
      greatest effect being observed after the use of 2-CdA and IFN-alpha at their
      highest concentrations.

PMID- 9017168
TI  - Psoriasis vulgaris with the early and late onset--HLA phenotype correlations.
AB  - The purpose of the study was to classify psoriasis vulgaris basing on HLA
      phenotype and the age of onset of the disease. One hundred fifteen psoriatic
      patients were included into the study and divided into two groups: group I--with
      early onset (< 40 years) and group II--with late onset (> or = 40 years). Each
      group was subclassified according to Cw6 antigen expression: IA-Cw(6+)--early
      onset, IB-Cw(6-)--early onset, IIA-Cw(6+)--late onset, IIB-Cw(6-)--late onset.
      HLA class I antigen typing was performed in each of 115 subjects using the
      microlymphocytotoxicity test. HLA class II antigen typing was also performed in
      20 randomly selected patients by means of the two-step microlymphocytotoxicity
      test. The occurrence Cw6, B13, B17 antigens was significantly increased in
      psoriatic groups in comparison with a control population. No difference between
      the groups was found with respect to class II antigen frequency. Cw6, B13 and B17
      were the most specific markers for psoriasis with the early onset, whereas B27,
      Cw2, B44 and Cw5 seemed to be associated with the late type of the disease.

PMID- 9017169
TI  - Immunohistochemical study in breast carcinoma. S100-protein positive cells and
      neuroendocrine differentiation.
AB  - In this study S100-protein positive cells were found in all 12 cases of benign
      dysplastic changes and in all of the investigated 53 cases of breast carcinomas.
      These cells belong to interdigitating cells (IDC) and were located in a regular
      pattern in the basal cell layer of the ducts and alveolar nodules in benign
      lesions. However, in breast carcinomas S100-protein positive IDC were in various
      pattern of distribution; only in the stroma, in basal cell layer, between cancer
      cells and S100-protein positivity of IDC and epithelial cancer cells. This
      phenomenon suggests the antigenic modulation of cancer cells transferring them
      the property of S100-protein positive cells or it may be the consequence of
      fusion. Immunoreactivity for chromogranin A (ChgA) and synaptophysin (Syn) was
      found in epithelial cells in some cases of benign dysplastic changes. However, in
      some carcinoma cases ChgA and Syn were revealed in carcinoma cells, in
      myoepithelial cells, in some stromal mesenchymal cells and endothelial cells.
      Immunoreactivity to smooth muscle actin was shown in the endothelial and smooth
      muscle cells of the vessel's wall, in myoepithelial cells and was also sporadic
      in carcinoma cells.

PMID- 9017170
TI  - We are the stories we tell.

PMID- 9017172
TI  - Damage to the primary dentition resulting from thumb and finger (digit) sucking.
AB  - It is estimated that approximately 50 percent of infants at one year of age suck
      a thumb or finger. The number decreases rapidly by ages four to five years. The
      average age for spontaneous cessation of the habit is 3.8 years of age. Anterior
      open bite is the most frequent malocclusion reported with digit sucking. In this
      study the authors investigated the influence of thumb and finger-sucking in the
      anterior and posterior sections of the primary dentition in three age-groups:
      three, four, and five years. The study population included 930 subjects. Data for
      the non-oral-habit group were compared with the data for the thumb and/ or finger
      sucking group. At all ages the frequencies of open-bite and maxillary protrusion
      for the thumb and finger-sucking group were higher than the non-oral-habit group.
      The frequencies did not appear age-related. There appeared to be an increased
      tendency to a permanent malocclusion in children who continued after four years
      of age.

PMID- 9017171
TI  - Effect of supervised use of an alum mouthrinse on dental caries incidence in
      caries-susceptible children: a pilot study.
AB  - Aluminum salts have demonstrated anticaries activity in a number of laboratory
      and animal studies. The aim of this double-blind, pilot, clinical trial was to
      evaluate the effect of an alum (Al) mouthrinse on dental caries formation both by
      itself and in combination with an ADA-approved sodium fluoride (F) dentifrice. A
      total of 260 caries-prone children residing in a low-F area were preselected for
      the study and scored independently for caries by two experienced examiners. After
      using gender, age, and initial DMFT(S) scores for baseline stratification, the
      subjects were assigned to one of three treatment regimens: (1) placebo mouthrinse
      and F dentifrice, (2) Al mouthrinse and placebo dentifrice, and (3) Al mouthrinse
      and F dentifrice. The alum mouthrinse contained 500 ppm Al and the sodium
      fluoride dentifrice contained 1100 ppm F. Rinsing was supervised at school on
      weekdays for 30 sec/day, while the dentifrices were used ad libitum at home.
      Subjects were reexamined for caries and oral health after six and twelve months.
      Both examiners found that children who used Al mouthrinse, in conjunction with
      either placebo or F dentifrices, had lower caries incidence than those who used
      placebo mouthrinse/F dentifrice combination; but the differences were
      statistically significant for only one of the examiners. No evidence of
      deleterious effects to the oral tissues was observed. The results of this pilot
      clinical trial demonstrated that daily supervised use of an alum mouthrinse
      inhibited caries development in decay-prone children at least as effectively as a
      F dentifrice.

PMID- 9017173
TI  - Phenobarbital-induced gingival overgrowth? Report of two cases and complications
      in management.
AB  - Gingival overgrowth is a known side effect of several seizure, immunosuppressant
      and calcium channel-blocker medications. Gingival overgrowth is not a reported
      side-effect of phenobarbital. This case report describes two patients with marked
      gingival overgrowth who had been medicated with phenobarbital exclusively since
      the initiation of seizure disorders. The clinical findings, surgical management,
      bleeding complications, and recommendations in management are discussed.

PMID- 9017174
TI  - Electronic apex locator: a useful tool for root canal treatment in the primary
      dentition.
AB  - The purpose of this study was to test the ability of an electronic apex locator,
      Root ZX to measure the root canal length in primary teeth with partial
      resorption. Twenty extracted primary molars were embedded in an alginate model
      imitating in vivo conditions. Root ZX and radiographic measurements were compared
      in dry and wet environments to the actual tooth length. Root ZX identified the
      tooth length at the most coronal portion of the resorption. The content of the
      root canal did not influence the results. No statistical differences were found
      between electronic, radiographic and actual tooth length measurements, although
      the radiographic measurements were longer than the electronic ones. It is
      suggested that Root ZX is a preferable auxiliary device to measure root canal
      length in the primary dentition.

PMID- 9017175
TI  - The use of hypnosis in a sedation clinic for dental extractions in children:
      report of 20 cases.
AB  - We report on the use of informal hypnotic imagery in a group of children who were
      unable to accept dental extractions under inhalation sedation and local
      anesthesia. Over the last two and a half years, one hundred and seventy-nine
      children have been seen in a sedation clinic at Newcastle Dental Hospital. In
      thirty-four cases it was necessary to stop treatment and from this group, twenty
      children were selected for the use of hypnotic imagery. Treatment was
      successfully completed in sixteen children and all parents who completed a
      written questionnaire (twelve) reported they were happy with their child's
      treatment. Our preliminary findings show hypnotic imagery can be used
      successfully as an adjunct to inhalation sedation and conventional management
      skills for dental extractions in children.

PMID- 9017176
TI  - The effectiveness of midazolam and hydroxyzine as sedative agents for young
      pediatric dental patients.
AB  - The purpose of the study was to compare hydroxyzine (HYD) and 0.2mg/Kg midazolam
      (MDZ) as sedative agents for young pediatric dental patients. Twenty-nine healthy
      two-to-four-year-old children participated in the study. Hydroxyzine was dripped
      nasally 10 minutes before treatment. The patient's crying, alertness, movement
      and general behavior were blindly assessed and statistically analyzed. No
      differences were found between the mean general behavior scores nor between the
      first and second visits in both groups. A significant difference (p < 0.02) was
      found in the acceptance of the face and nasal masks by children of the midazolam
      group between the first and second appointments. None of the children of this
      group cried nor moved at the first visit. The results of the study indicate that
      midazolam is somewhat more effective than hydroxyzine as a sedative agent for
      short procedures in young pediatric dental patients.

PMID- 9017177
TI  - Epidemiologic study of 19-month-old Edmonton, Alberta children: caries rates and
      risk factors.
AB  - A random sample of 938 19-month-old Edmonton children and their
      parents/caretakers were studied. Parents were interviewed and children were
      examined. Specimens for a caries activity test were collected at the examination.
      Results indicated 25 percent of the children had moderate to high caries
      activity, as shown by the Cariostat, with 4.6 percent showing decalcification
      lesions and frank caries. Early caries (BBTD) were found to be related to bottle
      feeding practices, discomfort with allowing the child to cry, and with mother
      being foreign-born. Foreign-born status was associated with the above parenting
      practices. Preferences for preventive recommendations and other descriptive
      results were reported.

PMID- 9017178
TI  - Are you treating youngsters who are or should be receiving mental health
      services?
AB  - Psychiatrists now recognize that the disorders of children are serious, treatable
      conditions and as precursors of adult psychopathology. These conditions can
      seriously influence the patient's behavior when undergoing dental treatment. The
      dentist will probably assume that the behavior problems are directly related to
      the nature of the dental service, rather than particular underlying personality
      characteristics of preschool and school-age children. It is important that
      practitioners recognize and understand these conditions as they attempt to
      provide adequate treatment. No national epidemiological studies have been
      conducted in this country that would provide valid indicators of either the
      prevalence or incidence of mental disorders among children. Local studies,
      however, have been done that diagnosable disorders in children range from 17.6
      percent to 22 percent, including 3 percent to 5 percent who have severe emotional
      or behavioral problems. The prevalence of many mental disorders is greater in
      males than in females, ranging from a ratio of 2:1 to 9:1. Lifetime prevalence of
      mental disorders, first diagnosed in infancy, childhood, and adolescence range as
      high as 15,000 cases per 100,000 persons. It is important for the dentist to
      recognize that (1) even the youngest of children seen in a dental practice may be
      in need of mental health services, (2) management problems may stem from mental
      health problems, and (3) families are unaware or unwilling to admit that a child
      may need help.

PMID- 9017179
TI  - Yes, overall crime statistics are down, but juveniles are committing more
      criminal offenses.
AB  - Despite a general national decline in criminal activities in the 1990s, juvenile
      criminal offenses continue to increase, (including violent, property, and
      delinquency acts). In addition increased numbers of children are being held in
      juvenile jails. It is all but impossible for pediatric health providers to think
      that "their patients" and "their practices" are immune from the epidemic of crime
      that affects and is caused by "just kids."

PMID- 9017180
TI  - Rehabilitation of young patients with amelogenesis imperfecta: a report of two
      cases.
AB  - This paper presents a method for the rehabilitation of young patients with
      amelogenesis imperfecta, illustrated by two cases. The method comprises a
      temporary phase and a transitory phase. The aim of the temporary phase, which
      involves the use of temporary resin and NiCr crowns during primary or mixed
      dentition, is to reestablish the esthetic, occlusal and masticatory features of
      the child's dentition. It must respect the integrity of the pulp so as not to
      compromise the development of the dentition, and must be capable of adapting to
      any changes occurring during development. The transitory phase, which is
      undertaken on the permanent teeth, ensures an esthetic quality that lasts until
      adulthood. It entails the use of laboratory designed composite prostheses.

PMID- 9017181
TI  - Fibrodysplasia ossificans progressiva: report of a case with guidelines for
      pediatric dental and anesthetic management.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare heritable disorder of
      progressive heterotopic ossification leading to joint ankylosis throughout the
      body. Permanent ankylosis of the jaw may be precipitated by minimal soft tissue
      trauma, a potentially devastating complication following routine dental care
      during childhood. Assiduous precautions are necessary in administering dental
      care to children who have FOP as exemplified in this case report. Routine dental
      prophylaxis is also necessary in order to minimize the need for invasive
      procedures.

PMID- 9017182
TI  - A mechanism for discharge of charged excitatory neurotransmitter.
AB  - Excitatory neurotransmitter is charged, so that emptying of a transmitter
      containing vesicle (discharge) would seem to require considerable energy. Even if
      the energy problem is surmounted and discharge thereby made possible, there is
      still a problem of making the discharge fast enough (considerably less than 1
      ms). Proposed here is a mechanism wherein discharge of charged transmitter is
      accompanied by the influx of cocharged ions or coefflux of counter-charged
      particles (ion interchange). It is shown theoretically that ion interchange
      obviates the necessity for a separate energy source and can provide the observed
      rapid vesicle discharge.

PMID- 9017183
TI  - Enzyme-inhibitor association thermodynamics: explicit and continuum solvent
      studies.
AB  - Studying the thermodynamics of biochemical association reactions at the
      microscopic level requires efficient sampling of the configurations of the
      reactants and solvent as a function of the reaction pathways. In most cases, the
      associating ligand and receptor have complementary interlocking shapes. Upon
      association, loosely connected or disconnected solvent cavities at and around the
      binding site are formed. Disconnected solvent regions lead to severe statistical
      sampling problems when simulations are performed with explicit solvent. It was
      recently proposed that, when such limitations are encountered, they might be
      overcome by the use of the grand canonical ensemble. Here we investigate one such
      case and report the association free energy profile (potential of mean force)
      between trypsin and benzamidine along a chosen reaction coordinate as calculated
      using the grand canonical Monte Carlo method. The free energy profile is also
      calculated for a continuum solvent model using the Poisson equation, and the
      results are compared to the explicit water simulations. The comparison shows that
      the continuum solvent approach is surprisingly successful in reproducing the
      explicit solvent simulation results. The Monte Carlo results are analyzed in
      detail with respect to solvation structure. In the binding site channel there are
      waters bridging the carbonyl oxygen groups of Asp189 with the NH2 groups of
      benzamidine, which are displaced upon inhibitor binding. A similar solvent
      bridging configuration has been seen in the crystal structure of trypsin
      complexed with bovine pancreatic trypsin inhibitor. The predicted locations of
      other internal waters are in very good agreement with the positions found in the
      crystal structures, which supports the accuracy of the simulations.

PMID- 9017185
TI  - In vivo photocycle of the Euglena gracilis photoreceptor.
AB  - We present the light-induced photocycle of the paraflagellar swelling of Euglena
      gracilis. The kinetics of this process was reconstructed by sampling its
      fluorescence emission and switching the excitation light from 365 nm to 436 nm.
      Stable intermediates in the photocycle were manifested. The measured millisecond
      resolution kinetics best fits a Michaelis-Menten equation. The data provide
      strong evidence that the paraflagellar swelling, a three-dimensional natural
      crystal of a light-detecting protein, is the true Euglena photoreceptor.

PMID- 9017184
TI  - Three-dimensional structure of the gap junction connexon.
AB  - The gap junction membrane channel is composed of macular aggregations of
      intercellular channels permitting the direct intercellular transfer of ions and
      small molecules. Each intercellular channel is formed by the apposition of two
      hexameric transmembrane channels (connexons), one from each cell. The
      interlocking of the two channels occurs extracellularly in a narrow 2.5-nm "gap"
      separating the junctional membranes. The channel-channel interaction is known to
      be selective between members of the family of proteins, called connexins, which
      oligomerize into the connexons. In addition to selectivity, the molecular
      interfaces involved in the extracellular interactions between connexons must be
      very congruent, since the intercellular channel must provide high resistances to
      the leakage of small ions between the channel lumen and the extracellular space.
      By using a recently developed biochemical procedure for obtaining ordered arrays
      of connexons from gap junctions split in the extracellular gap, (Ghoshroy, S., D.
      A. Goodenough, and G. E. Sosinsky. 1994. Preparation, characterization, and
      structure of half gap junctional layers spit with urea and EGTA. J. Membr. Biol.
      146:15-28) a three-dimensional reconstruction of a connexon has been obtained by
      electron crystallographic methods. This reconstruction emphasizes the structural
      asymmetry between the extracellular and cytoplasmic domains and assigns lobed
      structural features to the extracellular domains of the connexon. The implication
      of our hemichannel structure is discussed in relation to the in vivo state of
      unpaired connexons, which have been shown to exist in the plasma membrane.

PMID- 9017186
TI  - Conformation of a protein kinase C substrate NG(28-43), and its analog in aqueous
      and sodium dodecyl sulfate micelle solutions.
AB  - A peptide corresponding to the neuronal protein neurogranin (NG) residues 28-43,
      NG(28-43), and its analog, [A35]NG(28-43), have been investigated by NMR,
      electron paramagnetic resonance (EPR), and circular dichroism (CD)
      spectroscopies. The peptides existed in aqueous solution predominantly in random
      form. However, a nascent helical structure was detected in the central region of
      the parent peptide from NMR data. Furthermore, a helical structure can be
      detected for both peptides with greater induced secondary structure for the
      parent peptide in the presence of sodium dodecyl sulfate (SDS) micelle. The
      formation of micelles for SDS was confirmed by results from EPR as well as 13C
      NMR. As shown by CD experiments, helical conformer was induced for NG(28-43) in
      vesicular solution containing phosphatidyl serine (PS), whereas no helix can be
      discerned for the peptide in phosphatidyl choline (PC)-containing vesicular
      solution. Together with the induction of the peptide into helix in SDS micellar
      solution as suggested by both NMR and CD data, these results underscored the
      electrostatic contribution to the interaction of the PKC substrate peptides and
      proteins with membrane. According to NMR and CD data, a dynamic equilibrium
      existed between free and micelle-bound states for the peptide. Moreover, proton
      deuterium exchange results and SDS-induced linewidth broadening of proton
      resonances allowed delineation of the orientation of the amphipathic helix on the
      surface of SDS micelle. The result was supported by spin label experiments that
      indicated F35 of NG(28-43) interacted strongly with the hydrocarbon interior of
      micelle. Based on the experimental findings, a working model was proposed that
      attempted to partly explain the roles played by the nonpolar amino acid near the
      phosphorylation site, by the negatively charged phospholipids, and by the basic
      amino acids of the substrate.

PMID- 9017187
TI  - Time-resolved fluorescence spectroscopy and imaging of DNA labeled with DAPI and
      Hoechst 33342 using three-photon excitation.
AB  - We examined the fluorescence spectral properties of the DNA stains DAPI (4',6
      diamidino-2-phenylindole, hydrochloride) and Hoechst 33342 (bis-benzimide, or
      2,5'-bi'1H-benzimidazole2'-(4-ethoxyphenyl)-5-(4-methyl-1-piperazi nyl)) with two
      photon (2h nu) and three-photon (3h nu) excitation using femtosecond pulses from
      a Ti:sapphire laser from 830 to 885 nm. The mode of excitation of DAPI bound to
      DNA changed from two-photon at 830 nm to three-photon at 885 nm. In contrast,
      Hoechst 33342 displayed only two-photon excitation from 830 to 885 nm. DAPI-DNA
      displayed the same emission spectra and decay times for 2h nu and 3h nu
      excitation. Hoechst 33342-DNA displayed the same intensity decay for excitation
      at 830 and 885 nm. Both probes displayed higher anisotropies for multiphoton
      excitation as compared to one-photon excitation with ultraviolet wavelengths, and
      DAPI-DNA displays a higher anisotropy for 3h nu at 885 nm than for 2h nu at 830
      nm. We used 970-nm excitation of DAPI-stained chromosomes to obtain the first
      three-dimensional images with three-photon excitation. Three-photon excitation of
      DAPI-stained chromosomes at 970 nm was demonstrated by the power dependence in
      the fluorescence microscope.

PMID- 9017188
TI  - Phase sensitivity and entrainment in a modeled bursting neuron.
AB  - A model of neuron R15 in Aplysia was used to study the mechanisms determining the
      phase-response curve (PRC) of the cell in response to both extrinsic current
      pulses and modeled synaptic input and to compare entrainment predictions from
      PRCs with those from actual simulations. Over the range of stimulus parameters
      studied, the PRCs of the model exhibited minimal dependence upon stimulus
      amplitude, and a strong dependence upon stimulus duration. State-space analysis
      of the effect of transient current pulses provided several important insights
      into the relationship between the PRC and the underlying dynamics of the model,
      such as a correlation between the prestimulus concentration of Ca2+ and the
      poststimulus phase of the oscillation. The system nullclines were also found to
      provide well-defined limits upon the perturbatory extent of a hyperpolarizing
      input. These results demonstrated that experimentally applied current pulses are
      sufficient to determine the shape of the PRC in response to a synaptic input,
      provided that the duration of the current pulse is of a duration similar to that
      of the evoked synaptic current. Furthermore, we found that predictions of phase
      locked 1:m entrainment from PRCs were valid, even when the duration of the
      periodically applied pulses were a significant portion of the control limit
      cycle.

PMID- 9017189
TI  - Protein adsorption on surfaces with grafted polymers: a theoretical approach.
AB  - A general theoretical framework for studying the adsorption of protein molecules
      on surfaces with grafted polymers is presented. The approach is a generalization
      of the single-chain mean-field theory, in which the grafted polymer-protein
      solvent layer is assumed to be inhomogeneous in the direction perpendicular to
      the grafting surface. The theory enables the calculation of the adsorption
      isotherms of the protein as a function of the surface coverage of grafted
      polymers, concentration of protein in bulk, and type of solvent molecules. The
      potentials of mean force of the protein with the surface are calculated as a
      function of polymer surface coverage and amount of protein adsorbed. The theory
      is applied to model lysozyme on surfaces with grafted polyethylene oxide. The
      protein is modeled as spherical in solution, and it is assumed that the protein
      polymer, protein-solvent, and polymer-solvent attractive interactions are all
      equal. Therefore, the interactions determining the structure of the layer (beyond
      the bare polymer-surface and protein-surface interactions) are purely repulsive.
      The bare surface-protein interaction is taken from atomistic calculations by Lee
      and Park. For surfaces that do not have preferential attractions with the grafted
      polymer segments, the adsorption isotherms of lysozyme are independent of the
      polymer length for chains with more than 50 ethylene oxide units. However, the
      potentials of mean force show strong variations with grafted polymer molecular
      weight. The competition between different conformations of the adsorbed protein
      is studied in detail. The adsorption isotherms change qualitatively for surfaces
      with attractive interactions with ethylene oxide monomers. The protein adsorption
      is a function of chain length--the longer the polymer the more effective it is in
      preventing protein adsorption. The structure of the layer and its deformation
      upon protein adsorption are very important in determining the adsorption
      isotherms and the potentials of mean force.

PMID- 9017190
TI  - New model of charged molecule redistribution induced in spherical vesicles by
      direct current electric field.
AB  - A new electrophoresis model of charged components in a spherical phospholipid
      vesicle is proposed. In the new model the effective local tangential electric
      field is a result of the uniform external electric field modified by the electric
      field of redistributed charges. The modification is calculated on the basis of
      the Gouy-Chapman surface potential theory. Numerical calculations of steady-state
      distribution of charged molecules and the transmembrane potential are performed.
      The results show significant difference from the old, simplified model that
      neglects modification of the external electric field caused by redistributed
      charges.

PMID- 9017191
TI  - The contribution of electrostatic and van der Waals interactions to the
      stereospecificity of the reaction catalyzed by lactate dehydrogenase.
AB  - Continuum electrostatic calculations in conjunction with molecular dynamics
      simulations have been used to investigate the source of the stereospecificity in
      the hydride transfer reaction catalyzed by lactate dehydrogenase (LDH). These
      studies show that favorable electrostatic interactions between the carboxamide
      group of the reduced nicotinamide adenine dinucleotide coenzyme and protein
      residues of the active site of LDH can account for much if not all of the
      stereospecificity of the LDH-catalyzed reaction, with A-side hydride transfer
      more than 10(7) times greater than B-side transfer. Unfavorable steric
      interactions within the binding complex for B-side transfer are not found.

PMID- 9017192
TI  - Simulation studies of alamethicin-bilayer interactions.
AB  - Alamethicin is an alpha-helical peptide that forms voltage-activated ion
      channels. Experimental data suggest that channel formation occurs via voltage
      dependent insertion of alamethicin helices into lipid bilayers, followed by self
      assembly of inserted helices to form a parallel helix bundle. Changes in the kink
      angle of the alamethicin helix about its central proline residue have also been
      suggested to play a role in channel gating. Alamethicin helices generated by
      simulated annealing and restrained molecular dynamics adopt a kink angle similar
      to that in the x-ray crystal structure, even if such simulations start with an
      idealized unkinked helix. This suggests that the kinked helix represents a stable
      conformation of the molecule. Molecular dynamics simulations in the presence of a
      simple bilayer model and a transbilayer voltage difference are used to explore
      possible mechanisms of helix insertion. The bilayer is represented by a
      hydrophobicity potential. An alamethicin helix inserts spontaneously in the
      absence of a transbilayer voltage. Application of a cis positive voltage
      decreases the time to insertion. The helix kink angle fluctuates during the
      simulations. Insertion of the helix is associated with a decrease in the mean
      kink angle, thus helping the alamethicin molecule to span the bilayer. The
      simulation results are discussed in terms of models of alamethicin channel
      gating.

PMID- 9017194
TI  - The use of matrix methods in the modeling of spectroscopic data sets.
AB  - We describe a general approach to the model-based analysis of sets of
      spectroscopic data that is built upon the techniques of matrix analysis. A model
      hypothesis may often be expressed by writing a matrix of measured spectra as the
      product of a matrix of spectra of individual molecular species and a matrix of
      corresponding species populations as a function of experimental conditions. The
      modeling procedure then requires the simultaneous determination of a set of
      species spectra and a set of model parameters (from which the populations are
      derived), such that this product yields an optimal description of the measured
      spectra. This procedure may be implemented as an optimization problem in the
      space of the (possibly nonlinear) model parameters alone, coupled with the
      efficient solution of a corollary linear optimization problem using matrix
      decomposition methods to obtain a set of species spectra corresponding to any set
      of model parameters. Known species spectra, as well as other information and
      assumptions about spectral shapes, may be incorporated into this general
      framework, using parametrized analytical functional forms and basis-set
      techniques. The method by which assumed relationships between global features
      (e.g., peak positions) of different species spectra may be enforced in the
      modeling without otherwise specifying the shapes of the spectra will be shown. We
      also consider the effect of measurement errors on this approach and suggest
      extensions of the matrix-based least-squares procedures applicable to situations
      in which measurement errors may not be assumed to be normally distributed. A
      generalized analysis procedure is introduced for cases in which the species
      spectra vary with experimental conditions.

PMID- 9017193
TI  - Presynaptic calcium dynamics and transmitter release evoked by single action
      potentials at mammalian central synapses.
AB  - The relationship between presynaptic calcium transients ([Ca2+]t) and transmitter
      release evoked by a single stimulus was both investigated experimentally and
      modeled at a mammalian central synapse, the CA3 to CA1 pyramidal cell synapse in
      guinea pig hippocampal slices. In the present study, we compared the low-affinity
      calcium indicator furaptra with the higher-affinity indicator fura-2. The 10-90%
      rise time of the furaptra transient was 2.4 ms compared to 7.8 ms with fura-2;
      the half-decay time (tau 1/2) was 30 ms for furaptra, compared to 238 ms for fura
      2. The half-width of the calcium influx was 1.8 ms with furaptra, which provides
      an upper limit to the duration of the calcium current (ICa) evoked by an action
      potential. Modeling the decay time course of the furaptra transients led to the
      conclusion that the predominant endogenous calcium buffer in these terminals must
      have relatively slow kinetics (kon < 10(5)/M.s), although the presence of small
      amounts of fast buffers cannot be excluded. The relationship between the [Ca2+]t
      measured with furaptra and the postsynaptic response was the same as previously
      observed with fura-2: the postsynaptic response was proportional to about the
      fourth power (m approximately 4) of the amplitude of either [Ca2+]t or calcium
      influx. Thus, although fura-2 may be locally saturated by the high local [Ca2+]
      responsible for transmitter release, the volume-averaged fura-2 signal accurately
      reflects changes in this local concentration. The result that both indicators
      gave similar values for the power m constrains the amplitude of calcium influx in
      our model: Ica < 1 pA for 1 ms.

PMID- 9017195
TI  - Modeling buffered Ca2+ diffusion near the membrane: implications for secretion in
      neuroendocrine cells.
AB  - Secretion of catecholamines from neuroendocrine cells is relatively slow and it
      is likely that redistribution and buffering of Ca2+ is a major factor for
      delaying the response after a stimulus. In fact, in a recent study (Chow, R. H.,
      J. Klingauf, and E. Neher. 1994. Time course of Ca2+ concentration triggering
      exocytosis in neuroendocrine cells. Proc. Natl. Acad. Sci. U.S.A. 91:12765-12769)
      Chow et al. concluded that the concentration of free calcium ([Ca2+]i) at a
      release site peaks at < 10 microM during short-step depolarizations, and then
      decays to baseline over tens of milliseconds. To check whether such a time course
      is consistent with diffusion theory, we modeled buffered diffusion in the
      vicinity of a Ca2+ channel pore. Peak [Ca2+]i and the slow decay were well
      simulated when release-ready granules were randomly distributed within a regular
      grid of Ca2+ channels with mean interchannel distances of 300-600 nm. For such
      large spacings, however, the initial rise in [Ca2+]i was underestimated,
      suggesting that a small fraction of the release-ready pool (approximately 10%)
      experiences much higher [Ca2+]i, and thus might be colocalized with Ca2+
      channels. A model that accommodates these findings then correctly predicts many
      recent observations, including the result that single action potentials evoke
      near-synchronous transmitter release with low quantal yield, whereas trains of
      action potentials lead to desynchronized release, but with severalfold increased
      quantal yield. The simulations emphasize the role of Ca2+ not only in triggering,
      but also in modulating the secretory response: buffers are locally depleted by
      residual Ca2+ of a preceding stimulus, so that a second pulse leads to a larger
      peak [Ca2+]i at the fusion sites.

PMID- 9017196
TI  - Adaptation of single cardiac ryanodine receptor channels.
AB  - Single cardiac ryanodine receptor (RyR) channel adaptation was previously defined
      with Ca2+ stimuli produced by flash photolysis of DM-nitrophen (caged-Ca+2).
      Photolysis of DM-nitrophen induced a very fast Ca+2 overshoot (Ca+2 spike) at the
      leading edge of the Ca+2 stimuli. It has been suggested that adaptation (tau
      approximately 1.3 s) may reflect Ca+2 slowly coming off the RyR Ca+2 activation
      sites following the faster Ca+2 spike (tau approximately 1 ms). This concern was
      addressed by defining the Ca2+ deactivation kinetics of single RyR channels in
      response to a rapid reduction in free Ca2+ concentration ([Ca2+]FREE). The
      [Ca2+]FREE was lowered by photolysis of Diazo-2. Single RyR channels deactivated
      (tau approximately 5.3 ms) quickly in response to the photolytically induced
      [Ca2+]FREE reduction. Improved estimates of the Ca2+ spike time course indicate
      that the Ca2+ spike is considerably faster (10-100-fold) than previously thought.
      Our data suggest that single RyRs are not significantly activated by fast Ca2+
      spikes and that RyR adaptation is not due to deactivation following the fast Ca2+
      spike. Thus, RyR adaptation may have an important impact on Ca2+ signaling in
      heart.

PMID- 9017197
TI  - Modulation of the kinetics of inositol 1,4,5-trisphosphate-induced [Ca2+]i
      oscillations by calcium entry in pituitary gonadotrophs.
AB  - Inositol 1,4,5-trisphosphate (InsP3) binds to its receptor channels and causes
      liberation of Ca2+ from intracellular stores, frequently in an oscillatory
      manner. In addition to InsP3, the activation and inactivation properties of these
      intracellular channels are controlled by Ca2+. We studied the influence of Ca2+
      entry on the kinetics of InsP3-triggered oscillations in cytosolic calcium
      ([Ca2+]i) in gonadotrophs stimulated with gonadotropin-releasing hormone, an
      agonist that activates InsP3 production. The natural expression of voltage-gated
      Ca2+ channels (VGCC) in these cells was employed to manipulate Ca2+ entry by
      voltage clamping the cells at different membrane potentials (Vm). Under
      physiological conditions, the frequency of the GnRH-induced oscillations
      increased with time, while the amplitude decreased, until both reached stable
      values. However, in cells with Vm held at -50 mV or lower, both parameters
      progressively decreased until the signal was abolished. These effects were
      reverted by a depolarization of the membrane positive to -45 mV in both agonist-
      and InsP3-stimulated gonadotrophs. Depolarization also led to an increase in the
      fraction of time during which the [Ca2+]i remained elevated; this effect
      originated from both an increase in the mean duration of spikes and a decrease in
      the interval between spikes. The frequency and amplitude of spiking depended on
      the activity of VGCC, but displayed different temporal courses and voltage
      relationships. The depolarization-driven recovery of the frequency was
      instantaneous, whereas the recovery of the amplitude of spiking was more gradual.
      The midpoints of the Vm sensitivity curve for amplitude and duration of spiking (
      15 mV) were close to the value observed for L-type Ca2+ current and for
      depolarization-induced increase in [Ca2+]i, whereas this parameter was much lower
      (-35 mV) for interval between spikes and frequency of oscillations. These
      observations are compatible with at least two distinct effects of Ca2+ entry on
      the sustained [Ca2+]i oscillations. Calcium influx facilitates its liberation
      from intracellular stores by a direct and instantaneous action on the release
      mechanism. It also magnifies the Ca2+ signal and decreases the frequency because
      of its gradual effect on the reloading of intracellular stores.

PMID- 9017198
TI  - Activation-dependent subconductance levels in the drk1 K channel suggest a
      subunit basis for ion permeation and gating.
AB  - Ion permeation and channel opening are two fundamental properties of ion
      channels, the molecular bases of which are poorly understood. Channels can exist
      in two permeability states, open and closed. The relative amount of time a
      channel spends in the open conformation depends on the state of activation. In
      voltage-gated ion channels, activation involves movement of a charged voltage
      sensor, which is required for channel opening. Single-channel recordings of drk1
      K channels expressed in Xenopus oocytes suggested that intermediate current
      levels (sublevels) may be associated with transitions between the closed and open
      states. Because K channels are formed by four identical subunits, each
      contributing to the lining of the pore, it was hypothesized that these sublevels
      resulted from heteromeric pore conformations. A formal model based on this
      hypothesis predicted that sublevels should be more frequently observed in
      partially activated channels, in which some but not all subunits have undergone
      voltage-dependent conformational changes required for channel opening.
      Experiments using the drk1 K channel, as well as drk1 channels with mutations in
      the pore and in the voltage sensor, showed that the probability of visiting a
      sublevel correlated with voltage- and time-dependent changes in activation. A
      subunit basis is proposed for channel opening and permeation in which these
      processes are coupled.

PMID- 9017199
TI  - ATP-sensitive anion channel from rat brain synaptosomal membranes incorporated
      into planar lipid bilayers.
AB  - An anion channel was incorporated from rat brain synaptic plasma membrane
      fractions into planar lipid bilayers. The single-channel conductance was found to
      be 48.5 pS in choline-Cl solution (300 microM cis/100 microM trans). The anion
      selectivity of the channel was rather low (PCl/Pcholine = 1.7). The gating rate
      of the channel did not change with membrane potential over the range of -50 mV to
      50 mV. Several drugs, which are known as inhibitors of anion channels, were found
      to be efficient inhibitors for the synaptosomal anion channel. 4-Acetoamino-4'
      isothiocyanostilbene-2,2'-disulfonic acid, ethacrynic acid, indanyloxyacetic
      acid, and 5-nitro-2-(3-phenylpropylamino) benzoic acid inhibited the channel from
      the cis side of the membrane, corresponding to the cytoplasmic side of the plasma
      membrane. We found that the channel is regulated by intracellular ATP at
      millimolar concentrations. Other nucleotides, ADP and GTP, inhibited the channel
      as well. Glibenclamide, which is known as an inhibitor of an ATP-regulated
      potassium channel, inhibited the channel at micromolar concentrations from the
      trans side of the membrane. It is likely that the synaptosomal anion channel is a
      member of the ATP-binding cassette superfamily.

PMID- 9017200
TI  - The binomial model in fluctuation analysis of quantal neurotransmitter release.
AB  - The mathematics of the binomial model for quantal neurotransmitter release is
      considered in general terms, to explore what information might be extractable
      from statistical aspects of data. For an array of N statistically independent
      release sites, each with a release probability p, the compound binomial always
      pertains, with <m> = N<p>, p' identical to 1 - var(m)/<m> = <p> (1 + cvp2) and n'
      identical to <m>/p' = N/(1 + cvp2), where m is the output/stimulus and cvp2 is
      var(p)/<p>2. Unless n' is invariant with ambient conditions or stimulation
      paradigms, the simple binomial (cvp = 0) is untenable and n' is neither N nor the
      number of "active" sites or sites with a quantum available. At each site p =
      popA, whereas po is the output probability if a site is "eligible" or "filled"
      despite previous quantal discharge, and pA (eligibility probability) depends at
      least on the replenishment rate, po, and interstimulus time. Assuming stochastic
      replenishment, a simple algorithm allows calculation of the full statistical
      composition of outputs for any hypothetical combinations of po's and refill
      rates, for any stimulation paradigm and spontaneous release. A rise in n'
      (reduced cvp) tends to occur whenever po varies widely between sites, with a
      raised stimulation frequency or factors (tending to increase po's. Unlike <m> and
      var(m) at equilibrium, output changes early in trains of stimuli, and
      covariances, potentially provide information about whether changes in <m> reflect
      change in <po> or in <pA>. Formulae are derived for variance and third moments of
      postsynaptic responses, which depend on the quantal mix in the signals. A new,
      easily computed function, the area product, gives noise-unbiased variance of a
      series of synaptic signals and its peristimulus time distribution, which is
      modified by the unit channel composition of quantal responses and if the signals
      reflect mixed responses from synapses with different quantal time course.

PMID- 9017201
TI  - Involvement of the calcium inward current in cardiac impulse propagation:
      induction of unidirectional conduction block by nifedipine and reversal by Bay K
      8644.
AB  - In general, the fast sodium inward current (INa) is regarded as the main inward
      current ensuring fast and safe excitation of the normally polarized working
      myocardium. However, under conditions of locally delayed excitation in the
      millisecond range, the slow inward current (ICa) might additionally contribute to
      the success of impulse propagation. This hypothesis was tested in patterned
      growth cultures of neonatal rat ventricular myocytes, which consisted of narrow
      cell strands connected to large rectangular cell monolayers, where INa or ICa
      could be modified in the narrow cell strand adjacent to the expansion by a
      microsuperfusion system. As assessed during antegrade (strand-->expansion)
      propagation under control conditions using a system for multiple site optical
      recording of transmembrane voltage (MSORTV), this cell pattern gave either rise
      to local activation delays at the expansion ranging from 0.5 to 4 ms (dcontrol),
      or it induced undirectional conduction blocks (UCBs) in the antegrade direction.
      Irrespective of the size of dcontrol, suppression of the sodium current with
      tetrodotoxin confined to the cell strand adjacent to the expansion invariably
      induced UCB in the antegrade direction. If dcontrol was > 1 ms, UCB could also be
      elicited by suppression of ICa alone with nifedipine. Conversely, if UCB was
      present under control conditions, the inclusion of Bay K 8644 in the
      microsuperfusion established successful bidirectional conduction. These results
      suggest that ICa can be critically important for the success of impulse
      propagation across abrupt expansions of excitable tissue even if INa is not
      concurrently depressed.

PMID- 9017202
TI  - Interaction of bee venom melittin with zwitterionic and negatively charged
      phospholipid bilayers: a spin-label electron spin resonance study.
AB  - Electron spin resonance (ESR) spectroscopy was used to study the penetration and
      interaction of bee venom melittin with dimyristoylphosphatidylcholine (DMPC) and
      ditetradecylphosphatidylglycerol (DTPG) bilayer membranes. Melittin is a surface
      active, amphipathic peptide and serves as a useful model for a variety of
      membrane interactions, including those of presequences and signal peptides, as
      well as the charged subdomain of the cardiac regulatory protein phospholamban.
      Derivatives of phosphatidylcholine and phosphatidylglycerol spin-labeled at
      various positions along the sn-2 acyl chain were used to establish the chain
      flexibility gradient for the two membranes in the presence and absence of
      melittin. Negatively charged DTPG bilayer membranes showed a higher capacity for
      binding melittin without bilayer disruption than did membranes formed by the
      zwitterionic DMPC, demonstrating the electrostatic neutralization of bound
      melittin by DTPG. The temperature dependence of the ESR spectra showed that the
      gel-to-liquid crystalline phase transition is eliminated by binding melittin to
      DTPG bilayers, whereas a very broad transition remains in the case of DMPC
      bilayers. None of the spin labels used showed a two-component spectrum
      characteristic of a specific restriction of their chain motion by melittin, but
      the outer hyperfine splittings and effective chain order parameters were
      increased for all labels upon binding melittin. This indicates a reduced
      flexibility of the lipid chains induced by a surface orientation of the bound
      melittin. Whereas the characteristic shape of the chain flexibility gradient was
      maintained upon melittin addition to DMPC bilayers, the chain flexibility profile
      in DTPG bilayers was much more strongly perturbed. It was found that the steepest
      change in segmental flexibility was shifted toward the bilayer interior when
      melittin was bound to DTPG membranes, indicating a greater depth of penetration
      than in DMPC membranes. pH titration of stearic acid labeled at the C-5 position,
      used as a probe of interfacial interactions, showed net downward shifts in
      interfacial pK of 0.8 and 1.2 pH units contributed from the positive charge of
      melittin, outweighing upward shifts from interfacial dehydration, when melittin
      was bound to DTPG and DMPC, respectively. The perturbation of the outer hyperfine
      splitting was used to determine the interactions of melittin with spin-labeled
      lipids of different polar headgroups in DTPG and DMPC. Anionic lipids
      (phosphatidylserine, phosphatidylglycerol, and stearic acid) and zwitterionic
      lipids (phosphatidylethanolamine and phosphatidylcholine) had the largest outer
      splittings in the presence of melittin. Neutral lipids (protonated stearic acid
      and diacylglycerol) displayed the largest increase in outer splitting on binding
      melittin, which was attributed to a change in the vertical location of these
      lipids in the bilayer. Both effects were more pronounced in DTPG than in DMPC.

PMID- 9017203
TI  - Calorimetric and spectroscopic studies of the thermotropic phase behavior of the
      n-saturated 1,2-diacylphosphatidylglycerols.
AB  - The polymorphic phase behavior of a homologous series of n-saturated 1,2-diacyl
      phosphatidylglycerols (PGs) was studied by differential scanning calorimetry and
      Fourier transform infrared and 31P-nuclear magnetic resonance spectroscopy. When
      dispersed in aqueous media under physiologically relevant conditions, these
      compounds exhibit two thermotropic phase transitions that are structurally
      equivalent to the well-characterized pretransitons and gel/liquid-crystalline
      phase transitions exhibited by bilayers of the corresponding 1,2-diacyl
      phosphatidylcholines. Furthermore, when incubated at low temperatures, their gel
      phases spontaneously transform into one or more solid-like phases that appear to
      be highly ordered, quasicrystalline bilayers that are probably partially
      dehydrated. The quasicrystalline structures, which form upon short-term, low
      temperature annealing of these lipids, are meta-stable with respect to more
      stable structures, to which they eventually transform upon prolonged low
      temperature incubation. The rates of formation of the quasicrystalline phases of
      the PGs generally tend to decrease as hydrocarbon chain length increases, and PGs
      whose hydrocarbon chains contain an odd number of carbon atoms tend to be slower
      than those of neighboring even-numbered homologs. The calorimetric data also
      indicate that the quasicrystalline phases of these compounds become progressively
      less stable relative to both their gel and liquid-crystalline phases as the
      length of the hydrocarbon chain increases and that they decompose either to the
      liquid-crystalline phase (short- and medium-chain compounds) or to the normal gel
      phase (long-chain compounds) upon heating. The spectroscopic data indicate that
      although there is odd-even alternation in the structures of the quasicrystalline
      phases formed upon short-term low-temperature incubation of these compounds, the
      structural features of the stable quasicrystalline phases eventually formed are
      all similar. Furthermore, the degree of hydration and the nature of hydrogen
      bonding interactions in the headgroup and interfacial regions of these PG
      bilayers differ significantly from that observed in all other phospholipid
      bilayers studied so far. We suggest that many of the properties of PG bilayers
      can be rationalized by postulating that the glycerol moiety of the polar
      headgroup is directly involved in shielding the negative charges at the surface
      of the bilayer by means of hydration-like hydrogen bonding interactions with the
      phosphate moiety.

PMID- 9017205
TI  - Changes in the elastic properties of cholinergic synaptic vesicles as measured by
      atomic force microscopy.
AB  - Cholinergic synaptic vesicles from Torpedo californica have been probed with the
      atomic force microscope in aqueous buffers to map and measure their elastic
      properties. Elastic properties were mapped with a new atomic force microscope
      technique known as force mapping. Force mapping of vesicles showed that the
      centers of the vesicles are harder or stiffer than the peripheral areas in the
      three buffers that were investigated. These were an isoosmotic buffer, a
      hypoosmotic buffer, and an isoosmotic buffer with 5 mM CaCl2 added. The hardness
      of the vesicular centers was quantified by calculation of the elastic modulus.
      Elastic moduli were in the range of 2-13 x 10(5) Pa. Vesicular centers were
      hardest in calcium-containing buffer and softest in isoosmotic buffer. Hypotheses
      are presented for the composition and function of the hard centers.

PMID- 9017204
TI  - Bilayer interactions of indolicidin, a small antimicrobial peptide rich in
      tryptophan, proline, and basic amino acids.
AB  - Tryptophan, proline, and basic amino acids have all been implicated as being
      important in the assembly and structure of membrane proteins. Indolicidin, an
      antimicrobial 13-residue peptide-amide isolated from the cytoplasmic granules of
      bovine neutrophils, is highly enriched in these amino acids: five tryptophans,
      three prolines, three basic residues, and no acidic residues. Consistent with the
      likely importance of these amino acids in membrane protein assembly, indolicidin
      is known to be highly membrane-active and is believed to act by disruption of
      cell membranes. We have, therefore, examined the interactions of native
      indolicidin with large unilamellar vesicles (LUV) formed from
      palmitoyloleoylphosphatidylcholine (POPC), and
      palmitoyloleoylphosphatidylglycerol (POPG), in order to use it as a model system
      for studying membrane protein insertion and for evaluating the relative
      contributions of hydrophobic and electrostatic forces in peptide-bilayer
      interactions. Equilibrium dialysis measurements indicate that indolicidin binds
      strongly, but reversibly, to both neutral POPC and anionic POPG vesicles with
      free energies of transfer of -8.8 +/- 0.2 and -11.5 +/- 0.4 kcal/mol,
      respectively. The extremely strong partitioning into POPG vesicles necessitated
      the development of a new equilibrium dialysis method that is described in detail.
      Tryptophan fluorescence measurements show that indolicidin is located in the
      bilayer interface and that indole fluorescence is affected by the type of lipid
      used to form the LUVs. Circular dichroism (CD) measurements reveal unordered
      conformations in aqueous and bulk organic solutions and a somewhat more ordered,
      but not alpha-helical, conformation in SDS micelles and lipid bilayers.
      Fluorescence requenching measurements (Ladokhin et al. 1995. Biophys. J. 69:1964
      1971) on vesicles loaded with the fluorophore/quencher pair 8-aminonapthalene
      1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide (DPX), show that
      indolicidin induces membrane permeabilization. For anionic POPG, leakage is
      graded with a high preference for the release of cationic DPX over anionic ANTS.
      For neutral POPC vesicles no such preference is observed. Leakage induction is
      more effective with POPG vesicles than with POPC vesicles, as judged by three
      quantitative measures that are developed in the Appendix.

PMID- 9017206
TI  - Strain dependence of the elastic properties of force-producing cross-bridges in
      rigor skeletal muscle.
AB  - Stretch and release experiments carried out on skinned single fibers of frog
      skeletal muscle under rigor conditions indicate that the elastic properties of
      the fiber depend on strain. For modulation frequencies below 1000 Hz, the results
      show an increase in Young's modulus of 20% upon a stretch of 1 nm/half-sarcomere.
      Remarkably, the strain dependence of Young's modulus decreases at higher
      frequencies to about 10% upon a 1-nm/half-sarcomere stretch at a modulation
      frequency of 10 kHz. This suggests that the cause of the effect is less
      straightforward than originally believed: a simple slackening of the filaments
      would result in an equally large strain dependence at all frequencies, whereas
      strain-dependent properties of the actin filaments should show up most clearly at
      higher frequencies. We believe that the reduction of the strain dependence points
      to transitions of the cross-bridges between distinct force-producing states. This
      is consistent with the earlier observation that Young's modulus in rigor
      increases toward higher frequencies.

PMID- 9017207
TI  - Nucleotide-dependent contractile properties of Ca(2+)-activated fast and slow
      skeletal muscle fibers.
AB  - The relation between single skinned skeletal fiber contractile mechanics and the
      myosin mechanoenzyme was examined by perturbing the actomyosin interaction with
      the ATP analog CTP in fibers from both rabbit psoas and rat soleus. Tension,
      instantaneous stiffness, and the rate of tension redevelopment (ktr), under
      software-based sarcomere length control, were examined at 15 degrees C for a
      range of Ca2+ concentrations in both fiber types. CTP produced 94% of the maximum
      ATP-generated tension in psoas fibers and 77% in soleus fibers. In psoas, CTP
      also increased stiffness to 106% of the ATP stiffness, whereas in soleus
      stiffness decreased to 92%. Thus, part of the greater difference between maximum
      ATP- and CTP-generated tension in soleus fibers appears to be due to a decrease
      in strongly bound cross-bridge number. Interestingly, although the nucleotide
      exchange produced substantial increases in the steepness (nH) of the tension- and
      stiffness-pCa relationships in soleus fibers, only minor changes were seen in
      psoas fibers. At maximum Ca2+ and nominal P(i) levels, ktr in psoas fibers
      increased from 11.7 s-1 with ATP to 16.6 s-1 with CTP and in soleus fibers from
      4.9 to 8.4 s-1. Increased P(i) levels decreased the maximum Ca(2+)-activated
      tension in both fiber types and increased the ktr of psoas fibers, but the ktr of
      soleus fibers was not significantly altered. Thus, although the nucleotide
      exchange generally produced similar changes in the mechanics, there were
      significant muscle lineage differences in the tension- and stiffness-pCa
      relations and in the effects of P(i) on ktr, such that differences in contractile
      mechanics were lessened in the presence of CTP.

PMID- 9017208
TI  - The size and shape of caldesmon and its fragments in solution studied by dynamic
      light scattering and hydrodynamic model calculations.
AB  - The size and the shape of caldesmon as well as its 50-kDa central and 19-kDa C
      terminal fragments were investigated by photon correlation spectroscopy. The
      hydrodynamic radii, which have been calculated from the experimentally obtained
      translational diffusion coefficients, are 9.8 nm, 6.0 nm, and 2.9 nm,
      respectively. Moreover, the experimental values for the translational diffusion
      coefficients are compared with results obtained from hydrodynamic model
      calculations. Detailed models for the structure of caldesmon in solution are
      derived. The contour length is about 64 nm for all of the models used for
      caldesmon.

PMID- 9017209
TI  - Monitoring the myosin ATPase reaction using a sensitive fluorescent probe: pyrene
      labeled ATP.
AB  - A pyrene-labeled ATP (Pyr-ATP) in which a pyrene fluorophore is linked to the
      ribose moiety of ATP with a butyryl chain has been synthesized, together with the
      corresponding analog of ADP. The spectroscopic properties of two fluorescent
      analogs were found to be similar to those of 1-pyrenebutyric acid, making them
      photostable and highly sensitive probes for detecting changes in conformations
      around the nucleotide binding sites of proteins. Binding of Pyr-ADP to myosin
      subfragment-1 (S-1) resulted in a fluorescence quenching of about 70%. This
      binding was tight, with a dissociation constant (0.9 microM) similar to that of
      ADP itself. Formation of the stable ternary complex of Pyr-ADP with S-1 and
      orthovanadate could be monitored from the quench in pyrene fluorescence with a
      rate constant of 0.01 s-1. The final fluorescence intensity was about 20% of that
      for Pyr-ADP alone. Pyr-ATP was hydrolyzed by S-1 1.3 times faster than was ATP.
      Hydrolysis of Pyr-ATP was accompanied by an initial quenching of pyrene
      fluorescence with a subsequent recovery of the fluorescence. The fluorescence
      changes could be used to monitor the hydrolysis reaction continuously and measure
      the turnover rates of the analog. The fluorescence assay was sensitive,
      particularly under single turnover conditions, allowing hydrolysis reactions to
      be monitored at concentrations of S-1 and the analog as low as 50 nM.

PMID- 9017210
TI  - Disparate fluorescence properties of 2-[4'-(iodoacetamido)anilino]-naphthalene-6
      sulfonic acid attached to Cys-84 and Cys-35 of troponin C in cardiac muscle
      troponin.
AB  - Two monocysteine mutants of cardiac muscle troponin C, cTnC(C35S) and cTnC(C84S),
      were genetically generated and labeled with the fluorescent probe 2-[4'
      (iodoacetamido)anilino]naphthalene-6-sulfonic acid (IAANS) at Cys-84 and Cys-35,
      respectively. Cys-84 is located on helix D in the regulatory N-domain, and Cys-35
      is at the -y position of the inactive 12-residue loop of site I. These labeled
      mutants were studied by a variety of steady-state and time-resolved fluorescence
      methods. In the absence of divalent cation, the fluorescence of the attached
      IAANS indicated an exposed environment at Cys-35 and a relatively less-exposed
      environment at Cys-84. The binding of Ca2+ to the single regulatory site elicited
      a large enhancement of the emission of IAANS attached to Cys-84, but only
      marginal fluorescence changes of the probe at Cys-35. Upon reconstitution of the
      labeled cTnC mutants with troponin I and troponin T to form the three-subunit
      troponin, the fluorescence of IAANS-Cys-84 in apo-troponin was spectrally similar
      to that observed with the Ca(2+)-loaded uncomplexed cTnC mutant. Only very
      moderate changes in the fluorescence of IAANS-Cys-84 were observed when the
      regulatory site in reconstituted troponin was saturated. The exposed Cys-35
      environment of the uncomplexed cTnC mutant became considerably less exposed and
      less polar when the mutant was incorporated into apo-troponin. In contrast to the
      Cys-84 site, saturation of the regulatory site II by Ca2+ in reconstituted
      troponin resulted in a reversal of the environment of the Cys-35 site toward a
      more exposed and more polar environment. These results indicated involvement of
      the inactive loop I in the Ca2+ trigger mechanism in cardiac muscle. The
      fluorescence of IAANS at both Cys-84 and Cys-35 was sensitive to phosphorylation
      of cTnl in reconstituted troponin, and the sensitivity was observed with both apo
      troponin and Ca(2+)-loaded troponin.

PMID- 9017211
TI  - Graphical evaluation of alkylation of myosin's SH1 and SH2: the N-phenylmaleimide
      reaction.
AB  - Previous assertions about the effect of alkylation of SH1 and SH2 on the myosin
      high-salt calcium and EDTA ATPases have been summarized, and a simple procedure
      for obtaining the fractional labeling of SH1 and SH2 after treatment of myosin
      with alkylating agents has been derived. A simple graphical procedure for
      illustrating the degree of preference of a particular alkylating agent for SH1
      over SH2 has also been developed. The procedures we developed were validated by
      applying them to two previously studied compounds, 4-(2-iodoacetamido)-TEMPO and
      2,4-dinitrofluorobenzine, and then were used to determine a procedure for
      maximizing the extent of labeling of SH1 alone by N-phenylmaleimide, a compound
      not previously studied in this manner. It was found that approximately 80% of the
      SH1 sites could be alkylated without significant alkylation of SH2.

PMID- 9017212
TI  - Quantification of DNA patchiness using long-range correlation measures.
AB  - We introduce and develop new techniques to quantify DNA patchiness, and to
      quantify characteristics of its mosaic structure. These techniques, which involve
      calculating two functions, alpha(l) and beta(l), measure correlations at length
      scale l and detect distinct characteristic patch sizes embedded in scale
      invariant patch size distributions. Using these new methods, we address a number
      of issues relating to the mosaic structure of genomic DNA. We find several
      distinct characteristic patch sizes in certain genomic sequences, and compare,
      contrast, and quantify the correlation properties of different sequences,
      including a number of yeast, human, and prokaryotic sequences. We exclude the
      possibility that the correlation properties and the known mosaic structure of DNA
      can be explained either by simple Markov processes or by tandem repeats of
      dinucleotides. We find that the distinct patch sizes in all 16 yeast chromosomes
      are similar. Furthermore, we test the hypothesis that, for yeast, patchiness is
      caused by the alternation of coding and noncoding regions, and the hypothesis
      that in human sequences patchiness is related to repetitive sequences. We find
      that, by themselves, neither the alternation of coding and noncoding regions, nor
      repetitive sequences, can fully explain the long-range correlation properties of
      DNA.

PMID- 9017213
TI  - A computational approach to modeling nucleic acid hairpin structures.
AB  - Hairpin is a structural motif frequently observed in both RNA and DNA molecules.
      This motif is involved specifically in various biological functions (e.g., gene
      expression and regulation). To understand how these hairpin motifs perform their
      functions, it is important to study their structures. Compared to protein
      structural motifs, structures of nucleic acid hairpins are less known. Based on a
      set of reduced coordinates for describing nucleic acid structures and a sampling
      algorithm that equilibrates structures using Metropolis Monte Carlo simulation,
      we developed a method to model nucleic acid hairpin structures. This method was
      used to predict the structure of a DNA hairpin with a single-guanosine loop. The
      lowest energy structure from the ensemble of 200 sampled structures has a RMSD of
      < 1.5 A, from the structure determined using NMR. Additional constraints for the
      loop bases were introduced for modeling an RNA hairpin with two nucleotides in
      the loop. The modeled structure of this RNA hairpin has extensive base stacking
      and an extra hydrogen bond (between the CYT in the loop and a phosphate oxygen),
      as observed in the NMR structure.

PMID- 9017214
TI  - Mutation of a surface residue, lysine-129, reverses the order of proton release
      and uptake in bacteriorhodopsin; guanidine hydrochloride restores it.
AB  - K129 is a residue located in the extracellular loop connecting transmembrane
      helices D and E of bacteriorhodopsin. Replacement of K129 with a histidine alters
      the pKa's of two key residues in the proton transport pathway, D85, and the
      proton release group (probably E204); the resulting pigment has properties that
      differ markedly from the wild type. 1) In the unphotolyzed state of the K129H
      mutant, the pKa of D85 is 5.1 +/- 0.1 in 150 mM KCl (compared to approximately
      2.6 in the wild-type bacteriorhodopsin), whereas the unphotolyzed-state pKa of
      E204 decreases to 8.1 +/- 0.1 (from approximately 9.5 in the wild-type pigment).
      2) The pKa of E204 in the M state is 7.0 +/- 0.1 in K129H, compared to
      approximately 5.8 in the wild-type pigment. 3) As a result of the change in the
      pKa of E204 in M, the order of light-induced proton release and uptake exhibits a
      dependence on pH in K129H differing from that of the wild type: at neutral pH and
      moderate salt concentrations (150 mM KCl), light-induced proton uptake precedes
      proton release, whereas it follows proton release at higher pH. This pumping
      behavior is similar to that seen in a related bacterial rhodopsin,
      archaerhodopsin-1, which has a histidine in the position analogous to K129. 4) At
      alkaline pH, a substantial fraction of all-trans K129H pigment (approximately
      30%) undergoes a conversion into a shorter wavelength species, P480, with pKa
      approximately 8.1, close to the pKa of E204. 5) Guanidine hydrochloride lowers
      the pKa's of D85 and E204 in the ground state and the pKa of E204 in the M
      intermediate, and restores the normal order of proton release before uptake at
      neutral pH. 6) In the K129H mutant the coupling between D85 and E204 is weaker
      than in wild-type bacteriorhodopsin. In the unphotolyzed pigment, the change in
      the pKa's of either residue when the other changes its protonation state is only
      1.5 units compared to 4.9 units in wild-type bacteriorhodopsin. In the M state of
      photolyzed K129H pigment, the corresponding change is 1 unit, compared to 3.7
      units in the wild-type pigment. We suggest that K129 may be involved in
      stabilizing the hydrogen bonding network that couples E204 and D85. Substitution
      of K129 with a histidine residue causes structural changes that alter this
      coupling and affect the pKa's of E204 and D85.

PMID- 9017215
TI  - Theoretical study of the electrostatic and steric effects on the spectroscopic
      characteristics of the metal-ligand unit of heme proteins. 2. C-O vibrational
      frequencies, 17O isotropic chemical shifts, and nuclear quadrupole coupling
      constants.
AB  - The quantum chemical calculations, vibronic theory of activation, and London
      Pople approach are used to study the dependence of the C-O vibrational frequency,
      17O isotropic chemical shift, and nuclear quadrupole coupling constant on the
      distortion of the porphyrin ring and geometry of the CO coordination, changes in
      the iron-carbon and iron-imidazole distances, magnitude of the iron displacement
      out of the porphyrin plane, and presence of the charged groups in the heme
      environment. It is shown that only the electrostatic interactions can cause the
      variation of all these parameters experimentally observed in different heme
      proteins, and the heme distortions could modulate this variation. The
      correlations between the theoretically calculated parameters are shown to be
      close to the experimentally observed ones. The study of the effect of the
      electric field of the distal histidine shows that the presence of the four C-O
      vibrational bands in the infrared absorption spectra of the carbon monoxide
      complexes of different myoglobins and hemoglobins can be caused by the different
      orientations of the different tautomeric forms of the distal histidine. The
      dependence of the 17O isotropic chemical shift and nuclear quadrupole coupling
      constant on pH and the distal histidine substitution can be also explained from
      the same point of view.

PMID- 9017216
TI  - Energetics of cyclic dipeptide crystal packing and solvation.
AB  - Calculations of the thermodynamics of transfer of the cyclic alanine-alanine
      (cAA) and glycine-glycine (cGG) dipeptides between the gas, water, and crystal
      phases were carried out using a combination of molecular mechanics, normal mode
      analysis, and continuum electrostatics. The experimental gas-to-water solvation
      free energy and the enthalpy of gas-to-crystal transfer of cGG are accurately
      reproduced by the calculations. The enthalpies of cGG and cAA crystal-to-water
      transfer are close to the experimental values. A combination of experimental data
      and normal mode analysis of cGG provides an accurate estimate of the association
      entropy penalty (loss of rational and translational entropy and gain in
      vibrational entropy) for "binding" in the crystalline phase of -14.1 cal/mol/k.
      This is a smaller number than most previous theoretical estimates, but it is
      similar to previous experimental estimates. Calculated entropies of the crystal
      phase underestimate the experimental entropy by about 15 cal/mol/k because of
      neglect of long-range lattice motions. Comparison of the intermolecular
      interactions in the crystals of cGG and cAA provides a possible explanation of
      the puzzling decrease in enthalpy, with increasing hydrophobicity seen previously
      for both cyclic dipeptide dissolution and protein unfolding. This decrease arises
      from a favorable long-range electrostatic interaction between dipeptide molecules
      in the crystals, which is attenuated by the more hydrophobic side chains.

PMID- 9017217
TI  - A new metal-binding site for yeast phosphoglycerate kinase as determined by the
      use of a metal-ATP analog.
AB  - Suicide substrate beta, gamma-bidentate Rh(III)ATP (RhATP) was used to map the
      metal ion-binding site in yeast phosphoglycerate kinase (PGK). Cleavage of the
      RhATP-inactivated enzyme with pepsin and subsequent separation of peptides by
      reverse-phase high-performance liquid chromatography gave two Rh-nucleotide bound
      peptides. One of the peptides corresponded to the C-terminal residues of PGK, and
      the other to a part of helix V. Of the four glutamates present in the C-terminal
      peptide, Glu 398 may be a likely metal coordination site. Therefore, importance
      of the C-terminal residues in PGK catalysis may be attributed, in part to the
      coordination of metal ion of the metal-ATP substrate. Metal coordination may then
      align the C-terminal peptide to extend toward the N-terminal domain and form the
      "closed" active site. Results presented in this paper suggest that one or more
      side chains of the enzyme may be coordinated to the metal ion in the PGK.3
      phospho-D-glycerate-RhATP complex, and that exchange-inert metal-ATP analogs
      could be used to determine metal coordination sites on kinases and other metal
      ATP-utilizing enzymes.

PMID- 9017218
TI  - pH-dependent conformational changes in Escherichia coli dihydrofolate reductase
      revealed by Raman difference spectroscopy.
AB  - The catalytic site of all dihydrofolate reductases contains an invariant
      carboxylic acid, equivalent to Asp-27 in Escherichia coli dihydrofolate reductase
      (ecDHFR). It has been found that various kinetic and ligand binding properties of
      ecDHFR show a pH profile with a pKa of about 6.5. The group responsible for this
      pKa is often assumed to be carboxyl group of Asp-27. To determine the ionization
      state of this carboxyl and its pKa, we have employed a novel method, based on
      Raman difference spectroscopy, to obtain its vibrational spectrum in situ. The
      method is general for the study of protein carboxyl groups, which are often
      significantly implicated in protein function and structure; this study
      establishes the method's limits and problems. The Raman difference spectrum
      between wild-type ecDHFR and the Asp-27 to serine mutant (D27S) in the pH range
      5.6-9.0 has been taken. No protonation of the carboxyl group was detected,
      implying that its pKa is probably less than 5.0. We did, however, detect a pH
      dependence in the intensity of Raman bands in the difference spectrum with a pKa
      of 6.3, indicating that the apo enzyme undergoes a pH-dependent conformational
      change. Because the carboxyl group of Asp-27 at the active site is the only
      ionizable group in the binding site, other groups, away from the catalytic site,
      must be responsible for the pH behavior of ecDHFR.

PMID- 9017219
TI  - On a possible microscopic mechanism underlying the vapor pressure paradox.
AB  - We investigate the free energy and the profile of the displacement field in a
      stack of sterically interacting smectic multilayers bounded by surfaces under
      tension. We show that this tension can lead to a significant change in the
      multilayer free energy. It creates an additional long-range attraction (a pseudo
      Casimir attraction) of the van der Waals type and leads to a perturbation in the
      spatial profile of the displacement field fluctuations. This perturbation can
      extend to macroscopic distances into the multilayer, away from the perturbing
      surfaces. The lowering of the free energy of the layers varies explicitly as an
      inverse power of the thickness of the stack, but also depends implicitly on the
      bare interactions between the smectic layers. One may regard this lowered energy
      as being due to a kind of mechanical van der Waals force. We investigate in
      detail the characteristics and magnitude of the free energy as well as the
      fluctuations in the displacement field for some typical situations of underlying
      interlamellar interactions.

PMID- 9017220
TI  - On the role of assembly kinetics in determining the structure of clathrin cages.
AB  - The process of clathrin self-assembly into closed shells with the Fullerene
      structure is investigated. It is argued that the shell size distribution is
      governed by the kinetics of assembly and depends on the rate of growth controlled
      by the free clathrin concentration. The particularly abundant small structures-
      the "tennis ball" and the "hexagonal barrel"--are found to have a certain unique
      property that makes them ubiquitous in the process of slow growth. A thermal
      ratchet-type mechanism of the coated vesicle assembly on the membrane is
      proposed, and possible experimental tests are suggested.

PMID- 9017221
TI  - The conformation of DNA packaged in bacteriophage G.
AB  - When packaged in a bacteriophage capsid, double-stranded DNA occupies a cavity
      whose volume is roughly twice the volume of the DNA double helix. The data thus
      far have not revealed whether the compactness of packaged bacteriophage DNA is
      achieved by folding of the DNA, undirectional winding of the DNA, or a
      combination of both folding and winding. To assist in discriminating among these
      possibilities, the present study uses electron microscopy, together with
      ultraviolet light-induced DNA-DNA cross-linking, to obtain the following
      information about the conformation of DNA packaged in the comparatively large
      bacteriophage, G: 1) At the periphery of some negatively stained particles of
      bacteriophage G, electron microscopy reveals standards of DNA that are both
      parallel to each other and parallel to the polyhedral bacteriophage G capsid.
      However, these strands are not visible toward the center of the zone of packaged
      DNA. 2) Within some positively stained particles, electron microscopy reveals DNA
      associated stain in relatively high concentration at corners of the polyhedral
      bacteriophage G capsid. 3) When cross-linked DNA is expelled from its capsid
      during preparation for electron microscopy, some DNA molecules consist primarily
      of a compacted central region, surrounded by DNA strands that appear to be
      unravelling at multiple positions uniformly distributed around the compacted DNA
      region. The above results are explained by a previously presented model in which
      DNA is compacted by folding to form 12 icosahedrally arranged pear-shaped rings.

PMID- 9017223
TI  - Voltage-dependent potassium currents of sympathetic preganglionic neurons in
      neonatal rat spinal cord thin slices.
AB  - Voltage-dependent potassium currents were analyzed in the visually identified
      sympathetic preganglionic neurons (SPNs) of neonatal rat spinal cord thin slices
      by the whole-cell patch-clamp technique. Some of the SPNs were identified by the
      presence of retrogradely transported fluorescent dye, DiI, injected into the
      superior cervical ganglion several days prior to experimentation. In a
      tetrodotoxin (TTX)-containing solution, a step depolarization from the holding
      potential of -72 mV generated a slow outward current that was suppressed by
      tetraethylammonium (TEA) and by Ca(2+)-free/2.5 ImM Co2+ solution. Ca(2+)
      dependent current consisted of a transient and a sustained components. In a
      Ca(2+)-free (substituted with Mg2+) solution with TTX and TEA, a step
      depolarization from a hyperpolarized potential evoked a transient outward current
      that was blocked by 4-aminopyridine (4-AP). A step hyperpolarization evoked a
      voltage-dependent inward current, the conductance of which was dependent not only
      on the membrane potential, but also on the extracellular K+ concentration. Tail
      current analyses revealed that all of these currents were carried by K+ ions.
      These results indicate that SPN possesses at least five types of voltage
      dependent K+ current, including the delayed rectifier current (IK), Ca(2+)
      dependent transient current (IC), Ca(2+)-dependent sustained current (IAHP), A
      current (IA) and inward rectifying current (Iu), which may be targets of putative
      transmitters released from various descending and segmental inputs impinging upon
      the SPN.

PMID- 9017222
TI  - High-resolution scanning tunneling microscopy of fully hydrated ripple-phase
      bilayers.
AB  - A modified freeze-fracture replication technique for use with the scanning
      tunneling microscope (STM) has provided a quantitative, high-resolution
      description of the waveform and amplitude of rippled bilayers in the P beta'
      phase of dimyristoylphosphatidylcholine (DMPC) in excess water. The ripples are
      uniaxial and asymmetrical, with a temperature-dependent amplitude of 2.4 nm near
      the chain melting temperature that decreases to zero at the chain crystallization
      temperature. The wavelength of 11 nm does not change with temperature. The
      observed ripple shape and the temperature-induced structural changes are not
      predicted by any current theory. Calibration and reproducibility of the
      STM/replica technique were tested with replicas of well-characterized bilayers of
      cadmium arachidate on mica that provide regular 5.5-nm steps. STM images were
      analyzed using a cross-correlation averaging program to eliminate the effects of
      noise and the finite size and shapes of the metal grains that make up the
      replica. The correlation averaging allowed us to develop a composite ripple
      profile averaged over hundreds of individual ripples measured on different
      samples with different STM tips. The STM/replica technique avoids many of the
      previous artifacts of biological STM imaging and can be used to examine a variety
      of periodic hydrated lipid and protein samples at a lateral resolution of about 1
      nm and a vertical resolution of about 0.3 nm. This resolution is superior to
      conventional and tapping mode AFM to soft biological materials; the technique is
      substrate-free, and the conductive and chemically uniform replicas make image
      interpretation simple and direct.

PMID- 9017224
TI  - Increased proliferation of precursor cells in the adult rat brain after targeted
      lesioning.
AB  - There have been a number of reports on the proliferation of a subset of precursor
      cells in the subventricular zone of the lateral ventricles in the adult mammalian
      brain. Here we report on studies that sought to ascertain whether these cells
      could respond to a targeted lesion of the adult brain by increasing their
      proliferative rate. We have lesioned the fimbria fornix, a major pathway of
      septal cholinergic fibers. Previous reports demonstrated that such a lesion
      results in the loss of neurons in both the basal forebrain and in the CA1 field
      of hippocampus, without direct injury to either tissue. Ten days after making
      such a lesion in adult rats, the animals were given serial injections of
      [3H]thymidine and sacrificed after a final injection. The brains were processed
      for both immunocytochemistry and autoradiography. Our data demonstrate a two-fold
      increase over the basal proliferative rate in animals that had received such a
      lesion. We used a panel of antibodies to ascertain the identity of the
      proliferating cells. The only clearly identifiable cells that were [3H]thymidine
      positive were astrocytes, based on GFAP staining. The remainder of the cells were
      of a null phenotype.

PMID- 9017225
TI  - Attenuation of nociceptive responses by ACEA-1021, a competitive NMDA
      receptor/glycine site antagonist, in the mice.
AB  - Intrathecal administration of N-methyl-D-aspartate (NMDA) and non-NMDA receptor
      antagonists has been shown to produce antinociception in various animal models of
      pain. In the present study we examined the effect of 5-nitro-6,7-dichloro-1,4
      dihydro-2,3-quinoxalinedione (ACEA-1021), a competitive NMDA receptor/glycine
      site antagonist, on nociceptive responses in the tail flick and formalin tests in
      mice. Swiss Webster mice were injected with ACEA-1021 intraperitoneally (1-60
      mg/kg), or intrathecally (1-40 micrograms/mouse), and tested for antinociception.
      Systemic administration of ACEA-1021 attenuated the nociceptive responses solely
      in the formalin test. Nevertheless, intrathecal administration of ACEA-1021
      showed equally potent attenuation of nociceptive responses in both animal models
      of pain. The effect of ACEA-1021 was also examined on caudally directed biting
      and scratching (CDBS) behaviors induced by intrathecal administration of NMDA.
      Microinjections of NMDA (1-1000 microM) in the spinal cord produced dose
      dependent CDBS behaviors. Mice pretreated with ACEA-1021 (0.5-40
      micrograms/mouse) showed dose-dependent protection against CDBS behaviors induced
      by intrathecal NMDA. Taken together, the results suggest that ACEA-1021 may block
      spinal NMDA receptors to attenuate nociceptive responses, however, our data
      cannot exclude the involvement of non-NMDA receptors.

PMID- 9017226
TI  - Short latency, non-reciprocal group I inhibition is reduced during the stance
      phase of walking in humans.
AB  - Activation of group Ib afferents from extensor muscles produces an inhibition in
      the parent muscle and its synergists in a resting cat. This reflex switches to
      excitation of the parent muscle and its synergists when the cat walks. This study
      determined if a similar reflex undergoes the same type of reversal in the intact
      human. A putative Ib reflex was elicited by conditioning the Hoffmann (H) reflex
      in the soleus muscle with stimuli to the nerve innervating the medial
      gastrocnemius muscle. The reflex was observed while subjects: (1) sat quietly;
      (2) sat and activated the triceps surae muscle isometrically at a low level; (3)
      stood and activated the triceps surae to the same level as (2); and (4) walked on
      a treadmill. Condition-test intervals of 1 to 16 ms were used. Ten out of the 15
      subjects studied in quiet sitting showed an early, presumably disynaptic
      inhibition. Walking resulted in a significant reduction in the size of this
      inhibition at condition-test intervals of 4, 5, 6, and 8 ms for these subjects.
      No significant differences were observed at longer condition-test intervals. As a
      group, the inhibition of the conditioned H-reflex was diminished during walking,
      but not significantly excited. Four out of the 10 subjects, however, showed a
      significant excitation of the conditioned H-reflex during walking. The inhibition
      was significantly reduced at a condition-test interval of 7 ms when the triceps
      surae group was activated isometrically. No differences were seen in the reflex
      between matched levels of contraction in sitting and standing. It is concluded
      that the short latency group I inhibition seen at rest is reduced during walking,
      in a manner similar to that seen in spinal and decerebrate cats. The reduction
      may be accounted for, at least partially, by activation of the triceps surae.

PMID- 9017227
TI  - Vasopressin receptors in the mouse (Mus musculus) brain: sex-related expression
      in the medial preoptic area and hypothalamus.
AB  - We have investigated the distribution of vasopressin binding sites in the brain
      of male and female adult mice using a radio-iodinated ligand and film
      autoradiography. Vasopressin receptors were uncovered in various regions of the
      brain including the basal nucleus of Meynert, the substantia innominata, the
      hypothalamic paraventricular nucleus, the substantia nigra pars compacta and the
      hypoglossal nucleus. A sex-related difference in the expression of vasopressin
      receptors was seen in the medial preoptic area/anterior hypothalamus
      corresponding to the rat sexually dimorphic nucleus in the rat and in the
      hypothalamic mammillary nuclei. In both structures the autoradiographic labeling
      is more intense in females than in males. These observations confirm that
      vasopressin binding sites are present in the hypothalamic preoptic area of most
      species examined so far and that sex-related expression of neuropeptide receptors
      could trigger sex-related behavioral differences.

PMID- 9017228
TI  - The depolarisation-induced release of [125I]BDNF from brain tissue.
AB  - The pattern of release of radioactive brain-derived neurotrophic factor
      ([125I]BDNF) from brain tissue was studied. Rat brain slices from cerebral cortex
      and synaptosomes from cerebral cortex and hippocampus were preloaded with
      [125I]BDNF. Depolarising stimulation by veratridine (final conc. 50 microM) and
      high KCl (final conc. 45 mM) caused a short-term, greatly enhanced depolarisation
      induced release of [125I]BDNF during superfusion and batch protocol experiments.
      The results suggested that the evoked release was independent of the presence of
      extracellular calcium ions, but dependent on intracellular calcium ion stores,
      since the intracellular calcium ion chelator BAPTA-AM, but not the extracellular
      chelator EGTA abolished the high-potassium-induced [125I]BDNF release from
      synaptosomes. The release was blocked by tetrodotoxin (1 microM) when
      synaptosomes were stimulated by veratridine or potassium chloride. Short time
      fraction (30 s) superfusion experiments showed that the [125I]BDNF release from
      synaptosomes appeared in two temporal phases.

PMID- 9017229
TI  - Antidiuretic action of tachykinin NK-3 receptor in the rat paraventricular
      nucleus.
AB  - Studies were performed on the central antidiuretic actions via the tachykinin NK
      3 receptor in the rat hypothalamic paraventricular nucleus (PVN). Microinjections
      of the selective tachykinin NK-3 receptor agonist senktide (2-200 pmol) into the
      PVN resulted in prolonged inhibition of urine output in water-loaded rats, its
      effect being dose-dependent. The antidiuretic action of senktide was blocked by
      pretreatment with the vasopressin V2 receptor antagonist OPC-31260 (1 mg/kg,
      i.v.), but not by microinjection of the angiotensin II AT-1 receptor antagonist
      losartan (1 nmol) into the PVN. NK-3 receptor mRNA was strongly detected in the
      magnocellular part of the PVN and the supraoptic nucleus (SON) of the
      hypothalamus as detected by in situ hybridization histochemistry. Moreover,
      [3H]senktide binding sites were also detected in the PVN and the SON by receptor
      autoradiography. These findings suggest that NK-3 receptors in the PVN may be
      involved in water regulation by stimulation of vasopressin secretion from the
      posterior pituitary gland, and that vasopressin caused water reabsorbtion via the
      kidney V2 receptor.

PMID- 9017230
TI  - Postnatal retinal ganglion cells in vitro: protection against reactive oxygen
      species (ROS)-induced axonal degeneration by cocultured astrocytes.
AB  - Reactive oxygen species (ROS) are supposed to be involved in neurodegenerative
      processes like Parkinson's or Alzheimer's disease. Beside this there are an
      increasing number of studies indicating an involvement of ROS in traumatic brain
      injury. We therefore studied the potential role of astrocytes against neurotoxic
      effects of ROS in cocultures of rat cortical astrocytes with regenerating
      postnatal retinal ganglion cells (RGC). The sydnonimine SIN-1, which
      spontaneously decomposes to yield nitric oxide (NO) and superoxide anion
      radicals, led to axonal degeneration at concentrations between 1 microM and 10
      microM. Comparable effects were seen after addition of iron salts (Fe2+/Fe3+),
      which catalyze the generation of hydroxyl radicals. In contrast, in cocultures of
      RGC with astrocytes or after addition of free radical scavengers there was no
      neurotoxic/neurodegenerative effect of ROS as compared with control cultures.
      Vitamin E (1-10 microM) and vitamin C (10-100 microM) abolished the neurotoxic
      effect of both SIN-1 or iron ions. Beside this, there was an additional effect
      concerning the number and the length of neurites growing out from the retinal
      explant: in cocultures both parameters were greatly enhanced. These results
      suggest that (i) astrocytes are able to protect retinal ganglion cells against
      ROS-induced oxidative stress, (ii) astrocytes release soluble neurotrophic
      factors supporting RGC axonal regeneration, and (iii) free radical production
      after tissue injury may partly contribute to the failure of axonal regeneration
      in the adult mammalian central nervous system.

PMID- 9017231
TI  - Effects of generalized convulsive seizures on corticotropin-releasing factor
      neuronal systems.
AB  - Most stressors generate a set of endocrine and neural adaptations that form a
      stress response. The corticotropin-releasing factor neurons of the
      paraventricular nucleus of hypothalamus integrate endocrine and neural inputs,
      and cause a cascade of events with resultant increased levels of pituitary
      adrenocorticotropic hormone and adrenal hormones. Although activation of the
      hypothalamic-pituitary-adrenal axis is associated with a large variety of
      stressors, the effects of seizures on hypothalamic corticotropin-releasing factor
      neurons are essentially unknown. The goal of the present study was to elucidate
      the effects of generalized convulsive seizures on distinct and separate
      corticotropin-releasing factor cell populations in brain. Seizure-activated
      neurons were identified immunocytochemically through their expression of the Fos
      protein. Seizures were induced by intraperitoneal injection of kainic acid. In
      the paraventricular nucleus, the vast majority of corticotropin-releasing factor
      like parvocellular neurons also expressed Fos-like protein following seizure
      elicitation. This response was specific to corticotropin-releasing factor neurons
      of the paraventricular nucleus, as corticotropin-releasing factor neurons in
      central nucleus of the amygdala or bed nucleus of the stria terminalis did not
      simultaneously localize Fos following seizures.

PMID- 9017232
TI  - Role of nitric oxide in histamine-induced increases in permeability of the blood
      brain barrier.
AB  - While previous studies have examined the effects of histamine on the permeability
      of the blood-brain barrier and reactivity of cerebral blood vessels, cellular
      mechanisms which account for histamine-induced affects on the cerebral
      microcirculation are not clear. The goals of this study were to determine the
      role of nitric oxide in histamine-induced increases in permeability of the blood
      brain barrier and dilatation of pial arterioles. We examined the pial
      microcirculation in rats using intravital fluorescence microscopy. Permeability
      of the blood-brain barrier (clearance of fluorescent-labeled dextran; molecular
      weight 10,000 daltons; FITC-dextran-10K) and diameter of pial arterioles were
      measured in the absence and presence of histamine (10 and 100 microM). During
      superfusion with vehicle (saline), clearance of FITC-dextran-10K from pial
      vessels was minimal and diameter of pial arterioles remained constant. Topical
      application of histamine (10 and 100 microM) produced an increase in clearance of
      FITC-dextran-10K and diameter of pial arterioles. To determine a potential role
      for nitric oxide in histamine-induced increases in permeability of the blood
      brain barrier and dilatation of pial arterioles, we examined the effects of NG
      monomethyl-L-arginine (L-NMMA; 10 microM). L-NMMA inhibited histamine-induced
      increases in permeability of the blood-brain barrier and attenuated histamine
      induced dilatation of cerebral arterioles. The findings of the present study
      suggest that histamine increases permeability of the blood-brain barrier and
      diameter of pial arterioles via the synthesis/release of nitric oxide or a nitric
      oxide containing compound.

PMID- 9017233
TI  - Behavioral and neuroendocrine reactivity to stress in the WKHA/WKY inbred rat
      strains: a multifactorial and genetic analysis.
AB  - Genetic factors have been shown to influence the nature and the intensity of the
      stress responses. In order to understand better the genetic mechanisms involved,
      we have studied the behavioral and neuroendocrine responses to novel environments
      in the WKHA/WKY inbred strains and we have investigated the genetic relationships
      between these traits in a segregating F2 intercross. The animals were submitted
      to behavioral tests known to provide both indices of activity and fear (activity
      cages, open field and elevated plus-maze). The plasma levels of prolactin, ACTH,
      corticosterone, glucose and renin activity were determined after a 10-min
      exposure to novelty. Our results showed that WKHA rats, compared to WKYs, were
      more active in a familiar as well as in novel environments. They exhibited also
      less anxiety-related behaviors and lower neuroendocrine responses. A principal
      component analysis performed on the behavioral F2 results defined three
      independent factors: general activity, anxiety and defecation, none of them being
      correlated with the neuroendocrine measures. Thus this study suggests that these
      different responses to stress are independent components that may have distinct
      molecular bases.

PMID- 9017234
TI  - Descending modulation from the region of the locus coeruleus on nociceptive
      sensitivity in a rat model of inflammatory hyperalgesia.
AB  - The aim of the present study was to evaluate the action of the descending
      modulation system from the locus coeruleus (LC) in a rat model of unilateral
      hyperalgesic inflammation. Unilateral hindlimb inflammation was produced by a
      subcutaneous injection of carrageenan (6 mg in 0.15 ml saline). One week before
      testing, rats received bilateral lesions of the LC using anodal current.
      Nociception was assessed by measuring withdrawal of the paw from a noxious
      thermal stimulus. Four hours after carrageenan injection, paw withdrawal
      latencies (PWLs) in the inflamed paw of the LC-lesioned rats were significantly
      shorter than those of the sham-operated rats. This difference in PWL between the
      two groups was not observed at 7 days, whereas edema and hyperalgesia still
      remained in the inflamed paw. At 4 h, systemic naloxone produced a further
      decrease of the PWL in the LC-lesioned rats but not in the sham-operated rats.
      These results suggest that inflammation-induced activation of the descending
      modulation system from the LC occurs in only the acute phase of inflammation and
      that a decrease in the extent of the development of hyperalgesia in the acute
      phase of inflammation might depend on the interaction between the descending
      modulation system from the LC and the opioid inhibitory system.

PMID- 9017235
TI  - Thyrotropin-releasing hormone gene expression in the human hypothalamus.
AB  - We studied the distribution of mRNA coding for thyrotropin-releasing hormone
      (TRH) in the human hypothalamus by means of in situ hybridization. In 10%
      formalin-fixed paraffin-embedded tissue sections of five hypothalami, TRH mRNA
      containing cells were found in several nuclei and areas. Numerous TRH mRNA
      containing cells were detected in the medial region of the caudal part of the
      paraventricular nucleus. These neurons were heavily labeled and mainly small to
      medium-sized. Few, lightly- and medium-labeled, small cells were detected in the
      suprachiasmatic nucleus. In addition, heavily labeled single cells were found in
      the perifornical area and the anterior- and lateral hypothalamic regions. In the
      latter region, occasional heavily labeled cells were found just dorsal to the
      supraoptic nucleus. Neither in the supraoptic nucleus nor in the sexually
      dimorphic nucleus of the preoptic area were TRH mRNA-containing cells found. This
      is the first description of TRH mRNA containing cells in the human hypothalamus.

PMID- 9017236
TI  - Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in a
      rat model of mononeuropathy.
AB  - We have previously described the changes in spinal cord neuropeptides in the
      unilateral sciatic chronic constriction injury (CCI) model of Bennett and Xie
      [Pain, 33 (1988) 87-108] at 28 days, a time of maximum mechanical hyperalgesia.
      In this study we examine the same model 100-120 days post injury by which time
      resolution of the hyperalgesia and peripheral nerve injury has occurred according
      to previous studies. Rats underwent either CCI of the sciatic nerve (n = 12) or
      else sham operation (n = 8) which involved exposure but no ligation of the nerve.
      Mechanical hyperalgesia was assessed with a Ugo-Basile analgesymeter and
      immunohistochemistry performed on the spinal cord sections of the animals and
      quantified using a confocal microscope. At this late time point CCI rats were no
      longer significantly mechanically hyperalgesic compared to the sham animals (P >
      or = 0.09). However, examination of the lumbar spinal cord revealed the following
      changes. (i) The neuropeptides substance P (SP) (P < 0.0001) and galanin (P <
      0.003) both showed decreases of about 30% ipsilaterally in immunoreactivity in
      laminae 1 and 2 of the dorsal horn compared to the sham operated animals. (ii)
      Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in laminae 1 and
      2 showed no significant changes compared to sham animals. (iii) NPY levels in
      laminae 3 and 4 of the spinal cord showed a 15% increase in immunoreactivity
      compared to sham animals (P = 0.008). These results indicate that changes in
      neuronal markers in the spinal cord can persist after apparent resolution of a
      peripheral nerve injury. We suggest that these changes may form a substrate for
      subsequent development of abnormal pain states.

PMID- 9017237
TI  - In vitro hypoxia of cortical and hippocampal CA1 neurons: glutamate, nitric
      oxide, and platelet activating factor participate in the mechanism of selective
      neural death in CA1 neurons.
AB  - We prepared neuron-rich cultures from cortical and hippocampal CA1 regions of
      postnatal day 1 (P1) rats. Using these cultures, we investigated the sensitivity
      of neurons to hypoxic insults. The effects of MK-801, cycloheximide, NG-nitro-L
      arginine (L-NNA), and anti-platelet-activating factor (anti-PAF) IgG on neuronal
      injury under hypoxic conditions also were examined. The percentage of astroglial
      cells was higher in CA1 than cortical cultures despite use of the same culture
      procedure. Despite this finding, the percentage of lactate dehydrogenase (LDH)
      released into the medium was greater in CA1 than cortical cultures under the
      conditions of 24-h hypoxia and 24-h incubation (P < 0.05). We then added MK-801
      (500 nM), cycloheximide (3 microM), L-NNA (100 microM) and anti-PAF IgG (50
      micrograms/ml) prior to inducing the hypoxia and measured LDH in the medium after
      24-h hypoxia and 48-h incubation. Under the hypoxic condition, MK-801, L-NNA, and
      anti-PAF IgG significantly protected the CA1 neurons from hypoxic injury compared
      with cortical neurons, while cycloheximide protected both cultures equally. These
      results suggest that CA1 neurons are more sensitive to hypoxia than cerebral
      cortical neurons, and glutamate, nitric oxide, and PAF may participate in the
      mechanism of selective neural death in neurons of the CA1 region due to hypoxia.

PMID- 9017238
TI  - Electrical stimulation of the cingulum bundle and surrounding cortical tissue
      reduces formalin-test pain in the rat.
AB  - Surgical lesions of the cingulum bundle in humans produce marked decreases in
      severe pain associated with cancer, reflex sympathetic dystrophy and other forms
      of chronic pain. Similarly, a temporary block of the anterior cingulum bundle in
      the rat by microinjection of lidocaine produces significant decreases in formalin
      pain and reduces autotomy following peripheral neurectomy. The present study
      explored the effect of electrical stimulation of the cingulum bundle/surrounding
      cortical tissue (CB/CT) on tonic pain in the rat. Experiment 1 examined changes
      in formalin-induced pain responses following a 2.5-min period (30 s/min for 5
      min) of electrical stimulation of the CB/CT 15 min prior to the formalin
      injection. The stimulation produced a significant reduction of first-period and
      second-period pain responses. Experiment 2 examined changes in formalin-induced
      pain responses following a 2.5-min period (30 s/min for 5 min) of electrical
      stimulation of the CB/CT 20 min following the formalin injection. The stimulation
      produced a dramatic reduction in second-period pain responses which persisted for
      the duration of the 35-min post-stimulation test period. The fact that either
      electrical stimulation or surgical section of the CB/CT produces pain relief
      suggests that this region serves a complex role in pain processing. Since the
      cingulum bundle has major connections with all other structures of the limbic
      system, it is possible that electrical stimulation disrupts patterned activity in
      the system, which is known to play an especially important role in the affective
      motivational dimension of pain.

PMID- 9017239
TI  - Synergistic interaction between an adenosine antagonist and a D1 dopamine agonist
      on rotational behavior and striatal c-Fos induction in 6-hydroxydopamine-lesioned
      rats.
AB  - The interaction between adenosine and D1 dopamine systems in regulating motor
      behavior and striatal c-Fos expression was examined in rats with unilateral 6
      hydroxydopamine (6-OHDA) lesions. These results were compared to the synergistic
      interaction between D1 and D2 dopamine systems in 6-OHDA rats. Coadministration
      of the adenosine antagonist 3,7-dimethyl-1-propargylxanthine (DMPX: 10 mg/kg) and
      the D1 dopamine agonist SKF38393 (0.5 mg/kg) to 6-OHDA-lesioned rats produced
      significant contralateral rotation and c-Fos expression in the ipsilateral
      striatum compared to 6-OHDA rats treated with either drug alone. However, the
      regional pattern of striatal c-Fos activation following treatment of 6-OHDA rats
      with SKF38393 and DMPX was different from the dorsolateral pattern of striatal c
      Fos induction observed after coadministration of D1 and D2 dopamine agonists
      (SKF38393: 0.5 mg/kg + quinpirole: 0.05 mg/kg). These data are consistent with a
      functional interaction between D1 dopamine and adenosine systems in the striatum,
      but suggest that activation of different subsets of striatal neurons underlie the
      behavioral synergy observed following combined adenosine antagonist-D1 dopamine
      agonist and combined D1 dopamine agonist-D2 dopamine agonist treatment.

PMID- 9017240
TI  - Evidence for membrane remodeling in ipsilateral thalamus and amygdala following
      left amygdala-kindled seizures in awake rats.
AB  - We examined regional cerebral metabolic rates for glucose (rCMRglc) and brain
      incorporation coefficients (k*) of each of three intravenously infused fatty acid
      radiotracers, [9,10-(3H)]palmitate ([3H]PAM), [1-(14C)]arachidonate ([14C]AA) and
      [1-(14C)]docosahe-xaenoate ([14C]DHA), in awake rats fully kindled by once-daily
      electrical stimulation of the left amygdala. Compared with sham-stimulated
      animals, rCMRglc was increased bilaterally during a seizure, particularly in
      midbrain-brain stem regions, thalamus and basolateral nucleus of the amygdala. At
      24 h and 2 weeks after a seizure, there was no significant change in k* for
      either [14C]AA or [14C]DHA in any brain region, whereas k* for [3H]PAM at 24 h
      was increased significantly (by 32-53%) ipsilateral to stimulation in regions of
      the amygdala and thalamus. Contralateral regions showed no significant change.
      Two weeks after a seizure, k* for [3H]PAM was increased in the ipsilateral
      lateral dorsal nucleus of the thalamus. These results argue for membrane
      remodeling involving phosphatidylcholine in the ipsilateral amygdala and thalamus
      at the completed phase of amygdala kindling. Remodeling may continue for up to 2
      weeks after a seizure during the completed phase.

PMID- 9017241
TI  - Distribution of the organellar Ca2+ transport ATPase SERCA2 isoforms in the cat
      brain.
AB  - Of the three genes encoding the Ca2+ transport ATPases of the endoplasmic
      reticulum, the SERCA2 gene is the major isoform expressed in the mammalian brain.
      The SERCA2 transcript is alternatively processed generating two protein isoforms:
      SERCA2a which is expressed in cardiac and slow-skeletal muscle, and SERCA2b, the
      house-keeping isoform which is ubiquitously expressed. We have studied the
      expression of SERCA2 in the cat brain, and at a less refined level also in the
      rat brain, using antibodies specific for either SERCA2a or SERCA2b. The SERCA2a
      staining was very restricted. The SERCA2a antibody clearly labeled the cell body
      of the Purkinje neurons and weakly stained the giant cells of the gigantocellular
      reticular nuclei. In contrast, the SERCA2b isoform was found in most regions of
      the brain. It appeared to be largely confined to neuronal cells. Neuroglial cells
      were negative. The antibody stained the cell body. In heavily labeled cells such
      as the pyramidal cells of the hippocampus and of the cerebral cortex, it also
      stained the proximal portion of the dendrites. The most intense labeling was
      observed in the Purkinje neurons, which were stained all over the cell including
      the distal ramifications of the dendritic tree. Remarkably the SERCA2b labeling
      in neuronal cells of the hypothalamic area and the substantia nigra was very
      weak. The possible physiological significance of these results is discussed.

PMID- 9017242
TI  - Presumptive presynaptic nicotinic acetylcholine receptors in the chick tectum:
      effects of lesions of the lateral spiriform nucleus.
AB  - There are indications that nicotinic acetylcholine receptor subunits in the
      superficial layers of the chick tectum (Cajal's layers 1-7) may be transported
      from the retina. However, nicotinic receptor subunits are detectable by
      immunohistochemistry in all layers of the optic tectum. In this study, we
      performed unilateral electrolytic lesions of the lateral spiriform nucleus, which
      projects to the deep layers of the tectum and contains high amounts of nicotinic
      receptors in its perikarya. Following lesions of the lateral spiriform nucleus,
      both the alpha 5 and the beta 2 subunits were markedly depleted in the neuropil
      of the deep layers of the ipsilateral optic tectum (layers 8-13). No changes were
      observed in somata that contain either subunit. The present results suggest that
      most of the nicotinic acetylcholine receptor subunits in the chick optic tectum
      occur in axonal systems and could then constitute presynaptic receptors.

PMID- 9017243
TI  - Early auditory filial learning in degus (Octodon degus): behavioral and
      autoradiographic studies.
AB  - Degu mothers (Octodon degus) utter specific maternal calls during nursing which
      presumably stimulate and reinforce suckling. Pups from surgically muted mothers
      show a reduced gain of body weight during postnatal development compared to pups
      from normally vocalizing mothers. Our behavioral studies suggest that the pups
      have to learn the meaning of the maternal calls during the first two weeks of
      life. Two-week-old pups from normally vocalizing mothers expressed a preference
      for the maternal call in a behavioral discrimination test, in contrast to pups
      from surgically muted mothers. Investigation of brain activities using the 2
      [14C]fluoro-deoxyglucose (2-FDG) method revealed that pups from normal mothers
      display a significantly higher 2-FDG uptake in precentral medial, anterior
      cingulate cortex and a slight, non-significant increase in the prelimbic cortex
      and orbital PFC upon presentation of the maternal call, compared to pups from
      muted mothers, for which the maternal call was unfamiliar and meaningless. These
      prefrontal cortical areas are known to be involved in associative learning
      processes and our data suggest that they are involved in the association between
      the maternal call and the positive emotional situation during nursing.

PMID- 9017244
TI  - Putative excitatory amino acid projections to the suprachiasmatic nucleus in the
      rat.
AB  - Retrograde axonal transport of the select neuronal tracer [3H]D-aspartate was
      used to demonstrate possible sources of excitatory input to the suprachiasmatic
      nucleus (SCN) in the albino rat. Following injection of [3H]D-aspartate into the
      SCN, neurons were retrogradely labeled in the infralimbic cortex, the lateral
      septal nucleus, the paraventricular thalamic nucleus, the medial preoptic area,
      the ventromedial, dorsomedial and posterior hypothalamic nuclei, the zona
      incerta, the intergeniculate leaflet and the ventral subiculum. Retinal ganglion
      cells, which project to the SCN and use glutamate as a neurotransmitter, were not
      labeled in our [3H]D-aspartate experiments, demonstrating a limitation of this
      method (i.e., false negatives). Our results show that the [3H]D-aspartate
      neuronal tracer labels a subset of areas known to project to the SCN, indicating
      these areas as likely sources of excitatory input to the SCN.

PMID- 9017245
TI  - Brain penetration of the histamine H3 receptor antagonists thioperamide and
      clobenpropit in rat and mouse, determined with ex vivo [125I]iodophenpropit
      binding.
AB  - We investigated the brain penetration of the histamine H3 receptor antagonists
      thioperamide and clobenpropit using ex vivo [125I]iodophenpropit binding.
      Homogenates of the rat cortex, striatum and mouse whole brain were prepared 1 h
      after subcutaneous injection of the H3 antagonists and incubated with
      [125I]iodophenpropit, a radiolabeled H3 receptor antagonist, to determine the H3
      receptor occupancy. Specific [125I]iodophenpropit binding to the rat cortex and
      striatum was inhibited by thioperamide with IC30 values of 1.0 and 1.5 mg/kg,
      respectively. Clobenpropit also inhibited [125I]iodophenpropit binding, but was
      less potent (IC30: 18 and 19 mg/kg in the rat cortex and striatum, respectively)
      than thioperamide. Similar results were obtained in experiments with mouse whole
      brain (3.5 and 13 mg/kg for thioperamide and clobenpropit), indicating that there
      is no important species differences in the brain penetration of these drugs
      between rats and mice. These findings suggest that after peripheral injection
      both in rat and mouse thioperamide penetrates the blood-brain barrier more
      efficiently compared to clobenpropit.

PMID- 9017246
TI  - Opioid stimulation in the ventral tegmental area facilitates the onset of
      maternal behavior in rats.
AB  - This research investigated the effect of an increase or decrease in opioid
      activity in the ventral tegmental area (VTA) on the onset of maternal behavior in
      rats. In Experiment 1, the latency to show maternal behavior toward foster rat
      pups (sensitization latency) was determined in maternally naive female rats given
      either nothing or a unilateral intra-VTA injection of morphine sulfate (MS) (0.0,
      0.01, 0.03, 0.1 or 0.3 microgram), on the first three days of a 10-day period of
      constant exposure to pups. Rats treated with 0.03 microgram MS had significantly
      shorter sensitization latencies than did rats treated with 0.0 microgram MS, 0.01
      microgram MS, or receiving no treatment (higher doses of morphine produced
      intermediate results). The facilitating effect of intra-VTA MS on the onset of
      maternal behavior was blocked by pretreatment with naltrexone hydrochloride and
      was found to have a specific site of action in the VTA (MS injections dorsal to
      the VTA were ineffective). In Experiment 2, sensitization latencies were
      determined in periparturitional rats given a bilateral intra-VTA injection of
      either the opioid antagonist naltrexone methobromide (quaternary naltrexone), its
      vehicle, a sham injection, or left untreated 40 min after delivery of the last
      pup. The mothers' own pups were removed at delivery; mothers were nonmaternal at
      the time of testing. Quaternary naltrexone treatment produced significantly
      slower sensitization to foster pups than did control conditions. Total activity
      and pup-directed activity did not differ significantly with treatment. The
      results demonstrate that increased opioid activity in the VTA facilitates the
      onset of maternal behavior in inexperienced nonpregnant female rats, and
      decreased opioid activity in the VTA disrupts the rapid onset of maternal
      behavior at parturition.

PMID- 9017247
TI  - Muscarinic receptors mediate carbachol-induced phase shifts of circadian activity
      rhythms in Syrian hamsters.
AB  - Carbachol, a non-specific cholinergic agonist, when administered
      intraventricularly or directly into the suprachiasmatic nucleus (SCN), causes
      phase-dependent shifts in circadian rhythms of wheel-running activity in rodents.
      The cholinergic receptor subtype involved in mediating these carbachol-induced
      phase shifts, however, remains uncertain. In order to investigate this issue we
      injected carbachol into the SCN through indwelling cannulas at circadian times
      (CT) 6, 14 and 22 in Syrian hamsters (Mesocricetus auratus) maintained in
      constant darkness. Carbachol elicited large phase advances at CT 6 (69.8 +/- 15.7
      min; mean +/- S.E.M.) and CT 22 (83.9 +/- 24.8 min) and phase delays at CT 14
      (59.7 +/- 18 min). We attempted to block the carbachol-induced phase shifts at
      these three phases using specific antagonists of nicotinic and muscarinic
      receptors. Mecamylamine, a nicotinic receptor antagonist, did not block carbachol
      induced phase shifts at any of the phases tested. Atropine, a muscarinic receptor
      antagonist, blocked carbachol-induced phase shifts at CT 6 (-11.6 +/- 4.8 min;
      Mean phase shift +/- S.E.M.) and CT 22 (-20 +/- 6.6 min), suggesting that
      carbachol mediates its phase-shifting effects at these phases through muscarinic
      receptors.

PMID- 9017248
TI  - Effects of serotonin on induced epileptiform activity in CA1 pyramidal neurons of
      genetically epilepsy prone rats.
AB  - The seizure susceptibility in genetically epilepsy prone rats (GEPRs) is reported
      to be caused by abnormalities in several neurotransmitter systems including the
      serotonergic system. Among the reported abnormalities is a decrease in brain
      serotonin content. Therefore, we examined the effects of exogenous serotonin on
      brain slices from the severe seizure strain of GEPRs (GEPR-9s). We employed
      conventional electrophysiological techniques to record from CA1 pyramidal neurons
      of hippocampi of GEPR-9s. The membrane resting potential and input resistance of
      the GEPR-9 CA1 pyramidal neurons were not different from those of the Sprague
      Dawley rats. Serotonin (20 microM) inhibited the directly and synaptically evoked
      action potentials in GEPR-9 CA1 neurons, as it did in the Sprague Dawley neurons,
      but only in some and not all of the neurons tested (blocked the directly evoked
      potentials in 57% and synaptically evoked potentials in 33.3% of the total
      neurons). This inhibition was also accompanied by hyperpolarization and reduction
      of membrane input resistance. In the bicuculline-treated brain slices of the GEPR
      9, serotonin inhibited the epileptiform bursts causing concurrent
      hyperpolarization and reduction in membrane input resistance. The effects of the
      selective serotonin 5-HT1A receptor agonist, 8-OH-DPAT (20 microM) on GEPR-9
      pyramidal CA1 neurons were similar to those of serotonin, except the magnitude of
      hyperpolarization and reduction of membrane input resistance were less than those
      produced by serotonin. We conclude that the apparent decrease in sensitivity of
      the GEPR-9 CA1 pyramidal neurons to serotonin may represent a deficiency of
      serotonin 5-HT1A receptor.

PMID- 9017249
TI  - Topographic organization of projection from the parabigeminal nucleus to the
      superior colliculus in the ferret revealed with fluorescent latex microspheres.
AB  - Unilateral, discrete injections of red and green fluorescent latex microspheres
      or injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA
      HRP) were made into the ferret's superior colliculus (SC) to characterize the
      topographic organization of the projection from the parabigeminal nucleus (PBN).
      Retrograde labelling in the PBN revealed that this nucleus projects bilaterally
      to the SC, although the heaviest projection arises from the ipsilateral PBN. The
      PBN-SC projection demonstrates a highly ordered organization along the rostral
      caudal axis; rostral PBN projects to rostral SC and caudal PBN projects to caudal
      SC. The caudoventral and rostrodorsal areas of the PBN project mainly to the
      ipsilateral and contralateral SC, respectively. The ipsilateral pathway
      terminates principally in the caudal region of the SC, while the contralateral
      projection terminates predominantly in rostral SC. Ipsilaterally, there are
      slightly more neurons, located mainly in the ventral PBN, that project to the
      lateral SC than those, located largely in the dorsal part of the nucleus, that
      target the medial SC. The contralateral PBN mainly projects to the rostrolateral
      quadrant of the SC. These results indicate that each quadrant of the SC is
      innervated principally by a restricted part of the PBN: the caudolateral
      quadrant, which receives the heaviest ipsilateral input, and the caudomedial
      quadrant are targeted predominantly by the ventral and dorsal portions,
      respectively, of the ipsilateral PBN; the rostrolateral quadrant by the
      contralateral PBN, and the rostromedial quadrant, which receives the weakest
      input, by the dorsal portion of the nucleus on both sides. These findings suggest
      that activity in the PBN is relayed to distinct regions of the SC in the form of
      a highly ordered topographic projection. The adjacent lateral tegmentum (ALT)
      also projects heavily to the SC, principally on the ipsilateral side. The ALT
      projection to the ipsilateral SC appears to be organized in a less orderly
      fashion, and terminates principally in caudal SC, particularly the caudolateral
      quadrant. No topography was apparent for the contralateral projection.

PMID- 9017250
TI  - Involvement of N-methyl-D-aspartate receptor in the delayed transneuronal
      regression of substantia nigra neurons in rats.
AB  - The substantia nigra pars reticulata (SNr) receives both inhibitory GABAergic and
      excitatory glutamatergic afferents from diverse origins. Ischemic injury to the
      striatum and/or the globus pallidus causes delayed transneuronal death of the SNr
      neurons, in the course of which neuronal disinhibition induced by loss of
      GABAergic inputs is supposed to trigger a lethal hypermetabolic process. In the
      in vivo experiment presented herein, we clarified the role of glutamatergic
      action via the N-methyl-D-aspartate receptor in this cell death process.
      Continuous intraventricular infusion (0.5 microliter/h) of the N-methyl-D
      aspartate receptor antagonist MK-801 (1000 micrograms/ml), or of saline (control
      group) was initiated 24 h after 2 h of transient middle cerebral artery (MCA)
      occlusion in rats, by which massive ischemic injury was produced in the
      striatopallidal regions. The measured rectal temperature was not significantly
      altered in the MK-801-infused and in the control rats throughout the time period
      examined. The rats were killed at 15 days after MCA occlusion. The volume of the
      focal ischemic infarction of the MK-801-infused group did not significantly
      differ from that of controls. Also, MK-801-infusion did not significantly
      ameliorate the nigral atrophy subsequent to MCA occlusion. In association with a
      marked depletion of GABAergic afferent fibers, neuronal cell number in the
      ipsilateral SNr was significantly decreased in the control group. In contrast,
      the neuronal cell loss in the nucleus was completely prevented in the MK-801
      infusion group. The data suggested that withdrawal of GABAergic inputs may cause
      a severe imbalance between excitation and inhibition of the SNr neurons and may
      eventually result in neurotoxicity mediated by the N-methyl-D-aspartate receptor.
      Suppression of glutamatergic excitatory effects by suitable drugs may be a
      reasonable therapy for the transneuronal death of the SNr neurons.

PMID- 9017251
TI  - Serotonin depletion exacerbates changes in striatal gene expression following
      quinolinic acid injection.
AB  - Controversy exists as to whether serotonin (5-HT) plays a neuroprotective role
      during brain injury. We sought to determine if prior 5-HT depletion alters gene
      expression patterns normally associated with NMDA receptor-mediated
      excitotoxicity of the rodent striatum. Adult male Sprague-Dawley rats were
      treated systemically with saline or p-chlorophenylalanine (pCPA, 350 mg/kg) to
      block 5-HT synthesis. After 3 days, these rats received unilateral injection (1
      microliter) of quinolinic acid (QA, 40 micrograms in 0.1 M phosphate buffered
      saline, pH 7.4) or saline vehicle directly into the anterior striatum. All rats
      were sacrificed 6 or 48 h later. Striatal tissues containing the saline or QA
      injection site were subjected to Northern analysis of preprotachykinin (PPT),
      preproenkephalin (PPE), and zif/268 mRNAs, as well as HPLC-EC detection of
      monoamines. At the time of the intrastriatal injection, 5-HT levels were depleted
      greater than 95% by pCPA as compared to saline controls. At 48 h post-QA
      injection, PPT and PPE mRNAs were markedly reduced within the striatal lesion
      site of saline/QA and pCPA/QA groups with respect to their contralateral
      uninjected control sides. In the pCPA/QA group, striatal PPE and PPT mRNA levels
      were further reduced as compared to the saline/QA group with PPE mRNA reductions
      reaching statistical significance at 95% (ANOVA with Scheffe F-test).
      Exacerbation of the excitotoxic lesion in the 5-HT depleted rat was further
      exemplified by a larger increase in zif/268 mRNA measured at 6 h post
      intrastriatal injection in the pCPA/QA group as compared to saline/QA animals (P
      < 0.05 by ANOVA with Scheffe F-test). These results suggest that 5-HT depletion
      may adversely affect neuronal survival following intrastriatal QA exposure and
      lend support to the hypothesis that increasing 5-HT levels during NMDA receptor
      mediated excitotoxicity may spare neurons destined to degenerate.

PMID- 9017252
TI  - Brain beta-spectrin is a component of senile plaques in Alzheimer's disease.
AB  - Spectrin is a multifunctional cortical membrane skeleton protein. We report here
      that the beta-subunit of spectrin is an integral component of beta-amyloid
      plaques in Alzheimer's disease (AD). We prepared anti-beta-spectrin antibodies by
      using synthetic peptides corresponding to the N-terminal and C-terminal domains
      of beta-spectrin variants. When tissues from post-mortem AD brains were
      immunostained with these domain-specific affinity purified beta-spectrin
      antibodies, beta-amyloid plaques were specifically stained in the cortical
      parenchyma in approximately one third of the cases. The staining was unaffected
      by preadsorption of beta-spectrin antibodies with A4/beta 1-40 peptide. The
      sodium dodecyl sulfate-insoluble amyloids were also stained by the beta-spectrin
      antibodies. The anti-alpha-spectrin antibody stained neuronal processes, but not
      amyloid plaques. The presence of beta-spectrin in the amyloid plaques in a subset
      of sporadic AD cases suggests that distinct biochemical pathways are involved in
      the formation or deposition of beta-amyloid plaques, and that an abnormality of
      beta-spectrin structure or function may be involved in the formation or
      deposition of beta-amyloid plaques in this subset of AD cases.

PMID- 9017253
TI  - Protection against hypoxic-ischemic damage with corticosterone and dexamethasone:
      inhibition of effect by a glucocorticoid antagonist RU38486.
AB  - We investigated whether the neuroprotection provided by dexamethasone against
      neonatal hypoxic-ischemic damage can be inhibited by a glucocorticoid antagonist
      and whether corticosterone, the endogenous glucocorticoid in the rat, also
      provides protection. Rats (6 days old) were treated with either vehicle (0.1
      ml/10 g), corticosterone (3.5-80 mg/kg, s.c.) or dexamethasone alone or in
      combination with RU38486 (20-80 mg/kg, s.c.) 15 min prior to dexamethasone (0.1
      mg/kg, i.p.). At 7 days of age, cerebral hypoxia-ischemia was produced by right
      carotid artery ligation under anesthesia and subsequent exposure to 2 h of
      hypoxia. Damage was quantified from brains perfusion-fixed and processed 2 days
      later. The reduction in somatic growth, thymus weight and the relatively elevated
      blood glucose levels at the end of hypoxia-ischemia were inhibited by RU38486.
      The protective effect of dexamethasone was also prevented by RU38486 (P < 0.001).
      Similar to pre-treatment with dexamethasone, administration of corticosterone (40
      80 mg/kg) markedly reduced the extent of infarction compared to vehicle-treated
      controls (P < 0.0001). Thus, the endogenous glucocorticoid in the rat also
      provides protection against hypoxic-ischemic damage. RU38486 inhibits the
      beneficial effects of dexamethasone demonstrating that the neuroprotection
      observed with dexamethasone is a glucocorticoid receptor-mediated effect.

PMID- 9017254
TI  - Development of an animal model for neuroleptic malignant syndrome: heat-exposed
      rabbits with haloperidol and atropine administration exhibit increased muscle
      activity, hyperthermia, and high serum creatine phosphokinase level.
AB  - The neuroleptic malignant syndrome (NMS) is a life-threatening complication of
      neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has
      been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by
      intramuscular injection, were studied for the diagnostic symptoms of increased
      muscle rigidity, elevated body temperature, and high serum creatine phosphokinase
      (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg),
      and exposure to high ambient temperature (35 degrees C) induced a significant
      increase in electromyographic activity with muscle rigidity similar to that
      observed in patients with NMS. Such rabbits also showed elevated body temperature
      and serum CPK value. In addition to the similarity of the signs and symptoms, all
      parameters measured (muscle rigidity, body temperature, and serum CPK level) were
      normalized by dantrolene treatment. The effectiveness of dantrolene in the
      experimental animal partially confirms the validity of this animal model for NMS.
      This experimental animal model for NMS may be useful to elucidate the
      pathogenesis of NMS.

PMID- 9017255
TI  - Intraneuronal aluminum potentiates iron-induced oxidative stress in cultured rat
      hippocampal neurons.
AB  - Aluminum can facilitate Fe-mediated oxidative injury, which may contribute to Al
      neurotoxicity. It has been reported that Al potentiates Fe-induced oxidative
      stress in cultured granule cells, suggesting a mechanism for Al facilitation of
      Fe-mediated oxidative injury. However, the relationship of intracellular Al
      concentration to Fe-induced oxidative stress has not been reported. In the
      present study, neuronal oxidative stress and survival were investigated. Embryo
      rat hippocampal neuron cultures were treated with Al2(SO4)3 and/or FeSO4. An
      ionophore, A23187, was utilized to facilitate cellular Al uptake. Intraneuronal
      Al concentration was ascertained by laser microprobe mass spectrometry (LMMS).
      Neuronal oxidative stress was measured by confocal laser scanning microscopy,
      using 2,7-dichlorofluorescin diacetate (DCFH-DA) as a probe. The study showed
      that neuronal Al uptake was facilitated by the ionophore and that an increase of
      intraneuronal Al concentration potentiated Fe-induced oxidative stress and
      neuronal death. The results indicate that Al potentiation of Fe-induced oxidative
      stress might contribute to Al facilitation of oxidative injury, and thus to Al
      neurotoxicity.

PMID- 9017257
TI  - Noradrenaline modifies the spontaneous spiking activity of red nucleus neurons in
      the rat by activation of alpha 2- and beta-adrenoceptors.
AB  - We have investigated the effects of noradrenaline (NA) on the spontaneous firing
      activity of red nucleus (RN) neurons recorded extracellularly in anesthetized
      rats by using an in vivo electrophysiological technique. Microiontophoretic
      applications of NA (5-100 nA for 30 s) modified the background firing rate in 99
      out of 124 neurons and three different patterns of response were observed in
      distinct cells. In 61% of the responding neurons NA decreased the mean firing
      rate, whereas 22% of the neurons responded to NA application with an increase of
      their spiking activity; in a smaller group of cells (17%) NA exerted a biphasic
      inhibitory/excitatory effect on the spontaneous firing rate. The effects of NA
      were reversible and dose-dependent. From histological examination, the neurons
      responding to NA with a purely inhibitory effect were scattered throughout the
      RN. On the other hand, the neurons responding to NA with an excitation were found
      to be more numerous in the dorso-medial part of the RN, whereas the neurons in
      which NA induced biphasic effects appeared to be segregated in the outer lateral
      portion of the RN. The alpha 2-adrenoceptor antagonist yohimbine completely
      blocked the inhibitory effect of NA but was unable to antagonize the excitatory
      response. In addition, the inhibitory effect of NA was mimicked by clonidine, a
      selective agonist of alpha 2-adrenoceptors; clonidine had no effect on those
      cells which responded to NA with an increase of the mean firing rate. The
      excitatory effect of NA was mimicked by the beta-receptor agonist isoprenaline
      and was antagonized by timolol, a selective antagonist of beta-adrenoceptors.
      Isoprenaline was ineffective in those cells in which NA exerted inhibitory
      responses. Taken together, our results indicate that the inhibitory effect of NA
      on the firing activity of rat RN neurons were mediated by alpha 2-adrenoceptors,
      whereas beta-adrenoceptors were responsible for the excitatory effects.

PMID- 9017256
TI  - Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal
      neurons.
AB  - The neurotoxicity of L-DOPA and dopamine (DA) on striatal neurons was examined by
      using primary cultures of rat striatum. Exposure to L-DOPA and DA at
      concentrations of 30-300 microM induced dose-dependent cell death in both younger
      cultures (3 days in culture, 3 DIC) and elder cultures (10 days in culture, 10
      DIC). The cytotoxicity of L-DOPA and DA was also dependent on the exposure time
      (6-24 h). Ascorbic acid (200 microM) inhibited both L-DOPA- and DA-induced
      cytotoxicity in 3 DIC cultures, whereas it provided significant protection
      against DA- but not L-DOPA-induced cytotoxicity in 10 DIC cultures. The L-DOPA
      cytotoxicity in 10 DIC cultures was prevented by a non-NMDA receptor antagonist,
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and by an NMDA receptor antagonist,
      MK-801. Neither antagonist prevented DA cytotoxicity. D-DOPA did not affect the
      viability of 10 DIC cultures, though it elicited marked toxicity in 3 DIC
      cultures. These results suggest that there are two components in the mechanisms
      that mediate the L-DOPA neurotoxicity on striatal neurons: one is autoxidation
      relevant and the other is autoxidation-irrelevant. With respect to the latter,
      glutamate receptor stimulation may be involved. In contrast, autoxidation plays
      an important role in DA neurotoxicity.

PMID- 9017258
TI  - Vestibular afferents to the dorsal vagal complex: substrate for vestibular
      autonomic interactions in the rat.
AB  - Vestibular afferents to the nucleus tractus solitarii (NTS) were identified for
      the first time in the male Sprague-Dawley rat. Cells of vestibular origin were
      labeled by deposits of cholera toxin B (CT-B) centered on the general
      viscerosensory division of NTS and dorsal motor nucleus (DMX). Vestibular
      visceral afferents derive from neurons concentrated at caudal levels of medial
      and inferior vestibular nuclei as observed in other species. Vestibular afferent
      processes were labeled in the NTS and DMX by anterograde transport of the tracer,
      biotinylated dextran-amine from injection deposits confined to the inferior
      and/or medial vestibular nuclei. Vestibular axons terminate in the NTS,
      predominantly at intermediate levels of the dorsal vagal complex. Projections
      overlapped sites in NTS that receive terminal input from first-order alimentary
      and cardiorespiratory afferents. The somato-visceral reflex circuit corroborates
      recent evidence in the rat of increases in functional activity in the vestibular
      nuclear complex and NTS in response to changes in gravito-inertial force
      [Kaufman, G.D., Anderson, J.H. and Beitz, A.J., J. Neurosci., 12 (1992) 4489
      4500]. Vestibular input to the NTS and DMX may assist in compensating for the
      effects imposed by movements and gravity on breathing, alimentary reflex function
      and the systemic circulation.

PMID- 9017259
TI  - Properties of 3,4-diaminopyridine-evoked dopamine and acetylcholine release in
      rabbit caudate nucleus slices: involvement of facilitatory adenosine A2 receptors
      or nitric oxide?
AB  - The 3H-overflow from slices of the rabbit caudate nucleus preincubated with
      tritiated dopamine (DA), or choline, and then superfused and stimulated twice
      with 3,4-diaminopyridine (3,4-DAP; 25 microM, 1 min), was explored as an in vitro
      model for evoked release of DA, or acetylcholine (ACh), respectively. In both
      cases the 3,4-DAP-evoked 3H-overflow was tetrodotoxin-sensitive and Ca(2+)
      dependent and hence most probably represents action potential-induced exocytotic
      release of DA or ACh, respectively. Using pairs of preferential
      agonists/antagonists it was shown, that evoked DA release was inhibited via
      presynaptic D2 autoreceptors (quinpirole/domperidone) and kappa-opioid receptors
      (U-50488H/norbinaltorphimine). No evidence was found for the presence of
      presynaptic adenosine A1 or A2 receptors on dopaminergic terminals. Moreover, 3,4
      DAP-evoked DA release was unaffected by increased intracellular cyclic AMP levels
      or by drugs affecting the NO/guanylate cyclase pathway. In a similar manner it
      was shown that 3,4-DAP-evoked ACh release was inhibited via presynaptic muscarine
      autoreceptors (oxotremorine/atropine) and dopamine D2 heteroreceptors
      (quinpirole/domperidone). Again, no evidence for the involvement of the
      NO/guanylate cyclase system in the modulation of ACh release was found, whereas
      the presence of inhibitory adenosine A1 receptors, but not of facilitatory A2
      receptors, could be clearly established. It is concluded, that 3,4-DAP-evoked 3H
      overflow from rabbit caudate nucleus slices preincubated with [3H]DA or
      [3H]choline, represents a simple and useful in vitro model for action potential
      induced DA or ACh release, respectively. Moreover, at least in this model or
      rabbit brain region, facilitatory adenosine A2 receptors and the NO/guanylate
      cyclase system seem not to be involved in the release of these transmitters.

PMID- 9017260
TI  - Localization of the Rev-ErbA orphan receptors in the brain.
AB  - In the present study, we report the localization of the Rev-ErbA alpha and beta
      nuclear orphan receptors, two closely related members of the nuclear hormone
      receptor superfamily, in the brain. Both Rev-ErbA variant mRNAs were highly
      expressed in the olfactory bulb, the hippocampus, and in the granular cells of
      the cerebellum, areas enriched also in other nuclear orphan receptors.
      Furthermore, the alpha-isoform was found in high amounts in the frontal cortex,
      the superficial gray layer of the superior colliculus, and the stria terminalis.
      Lower expression was observed in the nucleus accumbens, the caudate-putamen, and
      in some thalamic and brainstem nuclei. The beta-variant, in contrast, was only
      moderately expressed in the cortex, mainly in the striate and retrosplenial
      cortices. In addition, moderate levels of Rev-ErbA beta mRNA were seen in various
      thalamic, pontine and brainstem nuclei. We conclude that the two Rev-ErbA
      isoforms share a partly similar pattern of expression in the brain, especially in
      areas that also contain other nuclear orphan receptors and that otherwise the
      localization of the two receptor subtypes is differential.

PMID- 9017261
TI  - Identification of a long huntingtin mRNA transcript in mouse brain.
AB  - Two mRNA species of the Huntington disease (HD) gene that share identical protein
      coding sequences but differ in their 3' untranslated region have been identified
      in human. Although a similar situation has been suggested to occur in mouse, only
      one cDNA has been isolated to date. We report the isolation of a novel partial
      cDNA of the mouse HD gene that is identical in its protein coding sequence to the
      previously reported cDNA, although it differs in the distal portion of the 3'
      untranslated region. Northern blotting assays indicate that this mRNA transcript
      is preferentially expressed in brain, with highest levels in cerebellum, cerebral
      cortex and striatum.

PMID- 9017262
TI  - Selective localisation of P450 enzymes and NADPH-P450 oxidoreductase in rat basal
      ganglia using anti-peptide antisera.
AB  - Environmental or endogenous toxins may cause nigral cell death in Parkinson's
      disease (PD) due to altered expression of P450 enzymes. In rat brain,
      immunohistochemistry using anti-peptide antisera showed NADPH-P450 oxidoreductase
      and CYP2B1/2 in various hypothalamic nuclei and CYP1A1 in the globus pallidus,
      but neither enzyme was expressed in substantia nigra. No specific
      immunoreactivity to CYP2D1 or CYP3A1 was found in any brain region examined. In
      contrast, CYP2E1 was expressed in substantia nigra and in striatal blood vessels.
      Since CYP2E1 is associated with free radical production, it may contribute to the
      oxidative stress believed to underlie nigral degeneration.

PMID- 9017263
TI  - Systemically administered cycloheximide reduces inhibition in rat neocortical
      slice preparation.
AB  - Global cerebral ischemia leads to long lasting hyperexcitability and a reduced
      protein synthesis in non-infarcted tissue surrounding the lesion. In this study
      we investigated whether protein synthesis inhibition by pharmacological means
      itself changes neocortical excitability. Two hours after the last of three i.p.
      injections with the protein synthesis inhibitor cycloheximide (12 h interval, 1.5
      mg/kg body weight) we observed a widespread reduction of neocortical inhibition.
      The study indicates that inhibition of protein synthesis may contribute to the
      altered brain excitability following ischemia.

PMID- 9017264
TI  - Time-related effects of stress on cholinergic sensitivity.
AB  - The effect of the administration of the muscarinic cholinergic agonist
      oxotremorine on locomotor activity was investigated in DBA/2 mice subjected to
      chronic restraint stress of different durations (120 min daily for 10, 14 or 18
      days). Oxotremorine induced a depressant effect on locomotion, which was reduced
      after 10 and 14 days of restraint, but not after a 18-day restraint stress.
      Acetylcholine (ACh) content was significantly reduced in prefrontal cortex after
      10 and 14 days of stress but returned to control values after 18 days of
      restraint. No changes in ACh content were observed in nucleus accumbens and
      striatum. These results are discussed in terms of possible changes in muscarinic
      receptor sensitivity.

PMID- 9017265
TI  - Differential cellular distribution of glutathione--an endogenous antioxidant--in
      the guinea pig inner ear.
AB  - Electronmicroscopic immunogold cytochemistry was applied to investigate the
      localization of glutathione (GSH) in the guinea pig inner ear. GSH
      immunoreactivity was preferentially distributed in basal cells and intermediate
      cells of the stria vascularis, and in fibrocytes and capillary endothelial cells
      in the spiral ligament and vestibular endorgans. The present findings suggest
      that the synthesis of GSH, a peptide known to protect against ototoxic compounds,
      depends on restricted cell populations in the inner ear.

PMID- 9017266
TI  - mu-Opioid receptor activation enhances DNA synthesis in immature
      oligodendrocytes.
AB  - Opioids disrupt nervous system development by inhibiting the proliferation of
      neuronal and glial progenitors. These studies explored the hypothesis that mu
      opioid receptors are expressed by immature oligodendrocytes (OLs) and are
      functionally related to growth. Antibodies identifying the cloned mu opioid
      receptor demonstrated that cultured OLs expressed mu opioid receptor
      immunoreactivity very early during development. Cultures were treated with the
      selective mu opioid receptor agonist H-Tyr-Pro-Phe (N-Me)-D-Pro-NH2 (PL017; 1
      microM), or PL017 (1 microM) plus the antagonist naloxone (3 microM). Opioid
      dependent changes in DNA synthesis were assessed by determining the proportion of
      bromodeoxyuridine (BrdU)-labeled O4-immunoreactive OLs. Treatment with PL017
      caused a 311% increase in the proportion of O4-immunoreactive OLs incorporating
      BrdU compared to untreated controls, and these effects were prevented by co
      administering naloxone. These preliminary results indicate that (i) immature OLs
      express mu opioid receptors and that (ii) the activation of this receptor type is
      functionally coupled to DNA synthesis and the cell division cycle. The expression
      of opioid receptors by OLs suggests that the endogenous opioid system is widely
      distributed among glial types.

PMID- 9017267
TI  - Cellular distribution of the NMDA receptor NR2A/2B subunits in the rat striatum.
AB  - Using immunohistochemical double-labeling with a specific antibody recognizing
      both NR2A and NR2B subunits, we studied the cellular distribution of the NMDA
      receptor subunit NR2A/2B on all major known striatal neuron types. Among striatal
      interneurons, our results showed that none of somatostatin interneurons was
      labeled for NR2A/2B subunits, 56% of parvalbumin interneurons were double-labeled
      for NR2A/2B, and all identified cholinergic interneurons were labeled for
      NR2A/2B. Among striatal projections neurons, 95% of striatonigral neurons, 96% of
      enkephalin-containing neurons, and 98% of calbindin-containing striatal matrix
      neurons were double-labeled for NR2A/2B. Our studies demonstrate that there is a
      differential distribution of the NMDA receptor NR2A/2B subunits on striatal
      neuron types. The paucity of NR2A/2B subunits on NMDA receptors on striatal
      somatostatin interneurons may confer resistance to NMDA receptor-mediated
      excitotoxicity on these neurons.

PMID- 9017268
TI  - Localization of nitric oxide synthase in the goldfish retina.
AB  - The localization of nitric oxide synthase and NADPH-diaphorase was studied in the
      goldfish retina by means of immunohistochemistry or tetrazolium salt technique.
      Nitric oxide synthase was found in some small neurons of the inner nuclear layer
      and in large neurons of the ganglion cell layer. The reaction product was
      localized in the outer plexiform layer and a diffuse labeling was also observed
      in the inner plexiform layer. In addition to the outer segments of
      photoreceptors, NADPH-diaphorase labeled several neurons of the inner nuclear
      layer and some neurons scattered in the ganglion cell layer. Both outer and inner
      plexiform layers were labeled. Ultrastructural observations showed that the
      reaction product was found to be bound to the endoplasmic membranes of positive
      neurons. In the outer plexiform layer the formazan precipitate labeled
      prevailingly the presynaptic terminals of rods and cones, in the inner plexiform
      layer both pre- and postsynaptic profiles showed the reaction product.

PMID- 9017269
TI  - R(+)-8-OH-DPAT, a 5-HT1A receptor agonist, inhibits amphetamine-induced serotonin
      and dopamine release in rat medial prefrontal cortex.
AB  - Pretreatment with R(+)-8-OH-DPAT, a selective serotonin (5-HT)1A receptor agonist
      (50 micrograms/kg, s.c.), inhibited D-amphetamine sulfate (1.0 mg/kg, s.c.)
      induced increases in extracellular levels of both 5-HT and dopamine (DA) in rat
      medial prefrontal cortex, as determined by in vivo microdialysis. The inhibitory
      effect of R(+)-8-OH-DPAT was completely reversed by the selective 5-HT1A receptor
      antagonist WAY 100,635 (100 micrograms/kg s.c.) administered 5 min prior to R(+)
      8-OH-DPAT. These results suggest that stimulation of 5-HT1A receptors may inhibit
      amphetamine-induced release of 5-HT and DA in the medial prefrontal cortex.

PMID- 9017270
TI  - Effect of systemic zinc administration on delayed neuronal death in the gerbil
      hippocampus.
AB  - The divalent cation zinc has been reported to possess several physiological
      properties such as blocking apoptotic cell death through an inhibitory effect on
      Ca(2+)-Mg2+ endonuclease activity, or modulating the neurotoxicity via glutamate
      receptor subtypes. In the present study, we investigated the effect of
      peripherally injected zinc on delayed neuronal death seen in the hippocampus
      after transient global ischemia, in order to elucidate a possible beneficial role
      on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of
      both sexes underwent transient bilateral clipping of the common carotid arteries
      for 3 min. In the pretreated animals, ZnCl2 (20 mg/kg) was injected
      subcutaneously once, 1 h before ischemia (superacute group; n = 6) or twice at 24
      and 48 h before ischemia (subacute group; n = 14). Histological survey was
      carried out 3 days later by in situ DNA fragmentation method and 4 days later by
      hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1
      sector. Subacute zinc pre-administration significantly reduced the nuclear damage
      and subsequent neuronal death; however, superacutely pre-administered zinc did
      not protect hippocampal neurons against ischemia but it did not aggravate the
      effect of ischemia, either. The present study suggested that transfer of
      exogenous zinc into the intracellular space is required for neuroprotection,
      presumably via the anti-endonuclease activity.

PMID- 9017271
TI  - The epidemiology of obesity.
AB  - An agreed definition of obesity as a body mass index (BMI) of 30 kg/m2 or more
      seems to be accepted everywhere except in North America. Recent data confirm the
      importance of setting an upper individual BMI limit of 25 kg/m2 and a population
      optimum of 20-23 kg/m2. Some adjustment of BMI should be made in individuals and
      populations with disproportionate shapes, e.g. short or long legs, and morbidity
      and mortality risks are especially important in those with a waist measurement of
      about 102 cm or more, the risk increasing from 88 cm. Waist measurements should
      probably now be substituted for the waist/hip circumference ratio. Diabetes is
      universally closely linked to increases in BMI, and cardiovascular disease is
      amplified by obesity, particularly in western societies where other dietary
      factors contribute substantially. Industrialization with reduced physical
      activity and higher fat diets lead to obesity first in middle-aged women, then in
      men, with younger adults and children eventually being affected. Physiological
      studies display the interaction of physical activity and energy dense, high fat
      diets and explain the secular, age- and social class-related trends throughout
      the world. Intergenerational amplification of obesity may be underway, so the
      public health implications of obesity are immense.

PMID- 9017272
TI  - Obesity in the Caribbean.
AB  - People of African origin who live in the Caribbean share a common genetic
      heritage but live in socioeconomic environments that diverge widely. A cross
      cultural study of males and females from Jamaica, St. Lucia and Barbados
      investigated the prevalence of hypertension and its environmental determinants.
      Standardized measurement techniques allowed comparable measurements of weight,
      height, waist and hip circumferences, and blood pressure. The population values
      for body mass index (BMI), per cent overweight (males BMI > or = 27.8 kg/m2;
      females BMI > or = 27.3 kg/m2) and per cent obese (males BMI > or = 31.1 kg/m2;
      females BMI > or = 32.3 kg/m2) are presented. Prevalence of hypertension is based
      on the age-adjusted total population. The gradient in per capita gross national
      product in Jamaica, St. Lucia and Barbados parallels the gradient in the
      proportions of population in those countries who are obese. BMI explained 26% of
      the variance in blood pressure in females and 13% in males. Obesity is a
      significant problem in the Caribbean, as it is in many other developing
      countries, and it is associated with a high prevalence of hypertension,
      particularly in women.

PMID- 9017274
TI  - Metabolic consequences of obesity and body fat pattern: lessons from migrant
      studies.
AB  - Prevalence of non-insulin-dependent diabetes mellitus and mortality from coronary
      heart disease are higher in people of South Asian (Indian, Pakistani and
      Bangladeshi) descent living in urban societies than in other ethnic groups. The
      high prevalence of diabetes is one manifestation of a pattern of metabolic
      disturbances related to central obesity and insulin resistance, which includes
      raised plasma very low density lipoprotein triglyceride and low plasma high
      density lipoprotein-cholesterol. Average waist/hip circumference ratios are
      higher in South Asians than in Europeans of similar body mass index: in this
      respect South Asians differ from other populations such as Pima Indians where
      high prevalence of non-insulin-dependent diabetes mellitus occurs in association
      with generalized obesity. The high rates of coronary heart disease in South
      Asians are most easily explained by the effects of this central obesity/insulin
      resistance syndrome, although ethnic differences in fasting lipids are unlikely
      to account fully for the excess risk. In Afro-Caribbean migrants, the prevalence
      of diabetes is almost as high as in South Asians but the lipid disturbances
      characteristic of the insulin resistance syndrome do not occur to the same
      extent. This may account for the low rates of coronary heart disease in this
      group.

PMID- 9017273
TI  - Obesity in peoples of the African diaspora.
AB  - People of African descent in the Caribbean and the USA originated from the Bight
      of Benin in West Africa. Although these populations share a common genetic
      heritage, they now live under different socioeconomical conditions. Assuming
      genetic similarity, a cross-cultural examination of these peoples in West Africa,
      the Caribbean and the USA may attenuate the effect of genetic factors and allow
      the assessment of environmental contributions to a biological outcome. We carried
      out an epidemiological survey to determine the prevalence of hypertension and the
      contribution of risk factors to the variation in blood pressure. We measured the
      height, weight, waist and hip circumferences, and blood pressure of adults in
      Nigeria, Cameroon, Jamaica, St. Lucia, Barbados and the USA. In urban populations
      there was a trend towards increasing weight, height, body mass index, and
      proportions of those overweight and obese going from West Africa to the USA, with
      the Caribbean being intermediate. The prevalence of hypertension lay on a similar
      gradient. Given a common genetic susceptibility, urbanization and western
      acculturation are therefore associated with increasing hypertension and obesity.

PMID- 9017275
TI  - The origins and consequences of obesity. Diabetes.
AB  - A relationship exists between obesity and non-insulin-dependent diabetes
      mellitus. Central, abdominal obesity carries a particularly high risk that is
      most likely associated with enlargement of visceral fat deposits. A multiple
      endocrine perturbation is associated with visceral obesity. This consists of a
      hypersensitive hypothalamic-pituitary-adrenal (HPA) axis, with resulting excess
      of cortisol secretion upon stimulation. Growth hormone levels in both sexes are
      diminished and testosterone concentrations in men are lower than normal. In women
      a moderate hyperandrogenism is often present. The elevated sensitivity of the HPA
      axis may be a primary event, followed by adrenal androgen production in women and
      by interaction at several levels, with inhibition of both the growth hormone and
      pituitary-gonadal axes. Together, these endocrine perturbations seem to be able
      to centralize body fat to visceral depots because of a high density of steroid
      hormone receptors. The endocrine perturbations are most likely followed by
      insulin resistance. Elevated cortisol levels, deficiencies in sex-specific
      steroid hormones and excess androgens result in insulin resistance. The endocrine
      abnormalities in visceral obesity are followed by insulin resistance, both
      directly and indirectly via contribution of excess free fatty acids from
      centralized body fat depots. The hyperactivity of the HPA axis may be due to
      frequent challenges and it is amplified by a deficient feedback inhibition. A
      depressive, helplessness reaction to stress may be involved. Such stress factors
      may be found in socioeconomic and psychosocial handicaps, as suggested by results
      of population studies. This hypothesis is strongly supported by the reproduction
      of an identical condition in non-human primates that react with a depressive
      reaction upon psychosocial types of stressors. The perturbations of the HPA axis
      may thus be in the centre of the syndrome. Studies of this axis in established
      non-insulin-dependent diabetes mellitus suggest similar perturbations, but the
      information is not conclusive.

PMID- 9017276
TI  - Obesity and cardiovascular disease.
AB  - The strong and consistent relationship observed between body weight and blood
      pressure develops early in life, and overweight/obesity in adult life is a good
      predictor of hypertension. Weight reduction leads to a decrease in blood pressure
      and prevention of weight increase lowers the incidence of hypertension, but
      obesity is not necessarily the direct cause of raised blood pressure. Obesity is
      not established as an independent risk factor for stroke beyond its association
      with other risk factors. Obesity is a relatively weak risk factor for coronary
      heart disease (CHD) but it is closely associated with almost all other coronary
      risk factors. Thus, becoming obese on a Western high fat diet, with development
      of excess central fat, promotes atherogenesis through a wide range of biochemical
      and hormonal parameters, including insulin sensitivity. The obesity-CHD
      relationship is further confused by the weight loss associated with smoking and
      smoking-related disease, and is confounded by risk factors that accompany the
      development and maintenance of obesity. Weight loss in middle-aged populations
      does not apparently lower CHD incidence, possibly because of lack of specificity
      in methods of weight reduction. Irrespective of the mechanisms involved, early
      prevention of atherogenic weight gain in young adulthood is an important public
      health goal towards the control of hypertension and CHD.

PMID- 9017277
TI  - Genetics of obesity in humans: current issues.
AB  - During the last decade, we have begun to understand some of the reasons why
      people become obese as assessed by excess body mass for height or excess total
      body fat content. Obesity frequently aggregates in families. However, this
      familial resemblance is caused not only by genetic effects but also by lifestyle,
      and environmental and cultural factors. Thus the genetic heritability of the
      obesity phenotypes accounts for up to 50% of the age- and gender-adjusted
      phenotypic variances. These results have been confirmed by overfeeding and
      negative energy balance studies. The effects of single segregating genes can be
      detected only under the correct experimental conditions. Most scientists in the
      area believe that these genes can be identified and that the DNA mutations
      associated with human obesities will be uncovered. Indeed, association and
      linkage studies, quantitative trait loci and positional cloning research
      strategies, and transgenic mouse models are sufficiently promising to suggest
      that these aims can be achieved. A review of the evidence reported thus far
      reveals that there are already four loci with strong evidence of linkage with
      obesity phenotypes in humans.

PMID- 9017278
TI  - Nutritional influences in early life upon obesity and body proportions.
AB  - Close relationships exist between patterns of intra-uterine growth and the risk
      of ischaemic heart disease, hypertension, diabetes, insulin-resistance syndrome,
      obesity and some cancers later in life. Earlier studies placed emphasis on low
      birth weight and reduced growth, but it is now clear that disproportions in early
      growth are of great importance. Disproportion may be identified as disproportions
      of fetal and placental growth (and the risk of high blood pressure), or in head
      circumference, length and weight. It is hypothesized that the availability of
      nutrients at different times during gestation, by interacting with the maternal
      and fetal hormonal profile, predisposes to different patterns of growth. The same
      interaction programmes critical metabolic functions and determines the metabolic
      capacity at all later ages. People who were exposed to severe undernutrition
      during the Dutch hunger winter showed increased adiposity if the exposure was
      during early pregnancy, but decreased adiposity if the exposure was during late
      pregnancy. In men born in the UK, those with evidence of retarded fetal growth
      had significantly greater waist/hip circumference ratios for any given body mass
      index (the ratio fell with increasing weight at one year of age). In Mexican
      Americans and non-Hispanic Caucasian Americans, people in the lowest third of
      birth weight had more truncal fat than those in the highest third. Offspring of
      rats exposed to marginally reduced protein intakes during pregnancy manifest a
      similar pattern of growth and metabolic change to that seen in humans, with
      perturbations of appetite and body fat patterning. Studies in rats suggest that
      programming of the hypothalamus, especially the hypothalamic-pituitary-adrenal
      axis might be the mechanism through which these changes are brought about.

PMID- 9017279
TI  - Overconsumption as a cause of weight gain: behavioural-physiological interactions
      in the control of food intake (appetite).
AB  - There is an asymmetry in the operation of physiological processes that maintain
      body weight. The body exerts a strong defence against undernutrition and weight
      loss, but applies a much weaker resistance to overconsumption and weight gain.
      These principles influence how appetite control operates and this constitutes one
      form of vulnerability to weight gain. The expression of appetite is reflected in
      an episodic pattern of eating behaviour, the selection of dietary commodities and
      an associated profile of conscious sensations such as hunger, preferences,
      aversions and fullness. The onset and termination of eating episodes are subject
      to facilitatory and inhibitory physiological processes, and are held in place by
      strong environmental contingencies and habitual routines. Energy intake resulting
      from physiological and environmental control of behaviour is generally in balance
      with energy expenditure, although changes in energy expenditure do not inevitably
      trigger changes in food intake. Excess energy intake over expenditure may be due
      to aberrant positive drive to seek energy or a permissive response to strong
      external stimuli. The former could arise from a defect in a lipostatic regulatory
      system, and the latter from the weakness of inhibitory signals or from strong
      facilitatory responses to superpotent physical features of food. Taste and
      textural qualities of food give rise to hedonic responses via opioidergic and
      aminergic systems. Inhibitory responses to macronutrients include adjustment of
      gastric volume, rate of gastric emptying, release of cholecystokinin and
      enterostatin, and changes in plasma levels of products of digestion. These
      peripheral responses lead to a series of changes in brain neurotransmitter
      networks. Proteins, fats and carbohydrates generate different sets of
      physiological responses that produce different effects on the intensity and
      duration of satiety. The nutrient composition of food and the overall energy
      density influence control of meal size and post-ingestive inhibition. Particular
      sensory and nutrient combinations in foods can facilitate passive
      overconsumption. Overriding physiological satiety signals can lead to a positive
      energy balance and weight gain.

PMID- 9017280
TI  - Obesity and metabolic efficiency.
AB  - Obesity has a strong genetic component, which should be viewed as a
      predisposition only if certain environmental factors are present. Impaired
      regulation of both sides of the energy balance equation plays a role in the
      propensity to gain weight and develop obesity. Overeating may be induced in
      susceptible individuals by high dietary fat content, large portion sizes and low
      meal frequency. Increased metabolic efficiency in the form of a low resting
      metabolic rate has been identified in pre- and post-obese subjects, and the
      impact on total energy expenditure may be amplified by a low level of physical
      activity. A low thermic effect of food has been shown not to be a risk factor for
      weight gain, and post-obese subjects have a normal thermic effect of food. A
      genetically determined enhanced metabolic efficiency during overfeeding has been
      reported to contribute to fat gain. The heterogeneous nature of obesity indicates
      that different mechanisms, such as changes in the partitioning of fat (due to
      lipoprotein lipase activity, fat oxidative muscle enzymes) and carbohydrate, and
      an altered responsiveness of the sympathoadrenal system and thyroid hormones to a
      positive energy balance, seem to be involved.

PMID- 9017281
TI  - Socioeconomic status and obesity.
AB  - Two recent developments have thrown into bold relief the importance of
      environmental forces in determining the prevalence of human obesity. The first is
      genetic studies that estimate the heritability of human obesity at no more than
      33%. The second is the 33% increase in the prevalence of obesity in the USA
      during the past decade. The importance of the environment in influencing obesity
      is matched only by the extent of our ignorance of how it exerts its effects and
      of how we may favourably alter them. The most thoroughly studied measure of
      environmental influences is socioeconomic status. Among women in developed
      societies socioeconomic status is strongly (negatively) correlated with the
      prevalence of obesity: the lower the social class the more the obesity.
      Prospective studies have shown that this correlation reflects, in part,
      causation: socioeconomic status helps to determine the prevalence of obesity and
      thinness. Likewise, the presence of obesity helps to determine socioeconomic
      status. In developing societies there is also a strong relationship between
      socioeconomic status and obesity, but it is a positive one: the higher the
      socioeconomic status the more the obesity. Unfortunately, we know of few other
      social determinants of obesity and studies on the social determinants of this
      disorder are desperately needed.

PMID- 9017282
TI  - The economic and psychosocial consequences of obesity.
AB  - Obesity is a multifaceted problem with wide-reaching medical, social and economic
      consequences. These are partly determined by the wealth and disease pattern of
      the population. In less-developed societies overweight may be advantageous and
      socially acceptable. In affluent societies obesity is a well-recognized health
      hazard and a socially stigmatized condition. For the obese person, excess weight
      denotes an increased risk of disabling chronic diseases, lowered quality of life
      and loss of earnings. For the society, obesity is a major economic burden.
      Treatment costs of diseases directly attributable to obesity are estimated to
      correspond to about 4-5% of the total health care expenditure. The indirect costs
      arising from loss of productivity due to obesity may be even higher.

PMID- 9017283
TI  - Obesity and physical activity.
AB  - This paper discusses the epidemiological evidence linking obesity to physical
      activity. The underlying plausible hypothesis is that the feedback from energy
      expenditure to appetite may be weak at low levels of physical activity and that
      sedentary lifestyles therefore favour positive energy balance and weight gain.
      Obesity is widespread in developed countries and appears to have a marked secular
      trend. An analysis of time-budget surveys reveals that the time required for
      earning a living and domestic work has declined appreciably over recent decades.
      This negative secular trend is associated with a substantial decline in the
      energy spent on these activities. The contraction of work time has resulted in a
      converse expansion of free time, but the bulk of this is spent on passive
      leisure. Thus, at least for western societies, the overall energy expenditure has
      fallen for some decades and lifestyles have become increasingly more sedentary.
      The review of a large data set on energy expenditure under free-living conditions
      indicates that, despite their phenomenally diverse rates of obesity, there is no
      systematic difference between developed and developing societies. Multivariate
      regression analysis of body mass index on physical activity level (PAL) reveals a
      weak but statistically significant inverse relationship in men but not in women,
      and establishes that the risk of obesity increases sharply at a PAL of less than
      1.80. In conclusion, a critical level of PAL has been identified, below which the
      chances of being overweight become substantial. The use of time is modelled
      contextually with its energy cost to show the extent to which energy expenditure
      may be modified. This has relevance from a policy standpoint, allowing a more
      focused approach for obesity prevention.

PMID- 9017284
TI  - Coherent, preventive and management strategies for obesity.
AB  - The increased risk of morbidity and mortality from obesity, central body fat and
      weight gain, and the benefits of weight reduction argue that the cost associated
      with obesity could be beneficially affected by prevention of weight gain or
      induction of weight loss. Genetic, metabolic and demographic predictors of weight
      gain have been identified that allow the selection of high risk individuals.
      Among the metabolic predictors are a low metabolic rate, insulin sensitivity and
      a high respiratory quotient. Demographic predictors include current smokers,
      certain dieting behaviours, lower socioeconomic class, a low level of education,
      use of contraceptives, status post-partum and rapid weight gain in childhood.
      Several studies suggest that weight gain can be prevented. Targets for such
      strategies might be high risk families, current smokers, those who are planning
      to stop smoking and those with a low metabolic rate. For those who fail primary
      prevention, treatment may be appropriate. The greater the degree of excess
      weight, the greater the risk and the more appropriate treatment becomes to reduce
      body weight.

PMID- 9017344
TI  - Epidemiology, classification, mechanism, and tolerance of human cervical spine
      injuries.
AB  - A review of published research is presented to examine human cervical spine
      injury epidemiology, classification, mechanism, and tolerance. Synthesis of the
      literature identifies several areas of cervical spine injury biomechanics in
      which the current understanding is greater than that suggested by individual
      investigations. Specifically, epidemiologic studies show an age dependent
      variation in the location of cervical spine injury. A classification scheme is
      developed on the basis of published work, in which the classes are defined by the
      resultant force acting at the site of injury. Further, for compression injuries
      it appears that a compression force tolerance criterion exists, and that
      eccentricity of the compressive force can be used to predict the type of cervical
      injury produced. However, to date, prediction of location of injury within the
      cervical spine has not been attempted. In particular, a compressive tolerance
      criterion is suggested between 2.75 and 3.44 kN for the adult cervical spine. In
      contrast, tolerance criteria for cervical injuries in other forms of loading are
      less well characterized. Review of the literature on spinal cord injury
      biomechanics and pediatric cervical spine injury reinforces the need for
      continued investigation in these areas.

PMID- 9017345
TI  - Finite element methods in spine biomechanics research.
AB  - The finite element method has been used in spine biomechanics research for nearly
      a quarter of a century. Recent developments have made it possible to simulate a
      variety of clinically relevant situations in an increasingly realistic manner,
      elevating the finite element method into a fully complementary partnership with
      experimental approaches for the investigation of clinical problems in the spine.
      These new developments are presented in a historical context to evaluate their
      potential impact on future spine biomechanics research.

PMID- 9017346
TI  - Body surface Laplacian electrocardiographic mapping--a review.
AB  - It is of great importance and significance to be able to noninvasively map
      spatially distributed cardiac electrical activity from body surface electrical
      recordings. The standard electrocardiographic monitoring techniques provide
      little spatial information regarding cardiac electrical activity. Recently, a new
      approach-body surface Laplacian electrocardiographic mapping-has been
      aggressively pursued to provide high-resolution spatial mapping of cardiac
      electrical activity. The fundamental innovation is the measurement of the
      Laplacian electrocardiogram distribution over the body surface. The body surface
      Laplacian electrocardiographic maps have been shown to provide enhanced ability
      to map multiple spatially separate cardiac bioelectric sources. This article
      reviews the theoretical and experimental aspects of this emerging mapping
      technique. First of all, the paper briefly reviews the historical development of
      body surface mapping and inverse solutions for mapping the distributed cardiac
      electrical activity. Then the paper reviews the theoretical basis of body surface
      Laplacian mapping and the biophysical interpretation of body surface Laplacian
      signals, as well as technical consideration of the Laplacian recording and
      instrumentation. Investigations of body surface Laplacian maps in computer models
      and a physical tank model, as well as physiological studies are also reviewed.

PMID- 9017347
TI  - The costs of non-insulin-dependent diabetes mellitus.

PMID- 9017348
TI  - Diabetes in British south Asians: nature, nurture, and culture.
AB  - Diabetes mellitus and its complications account for a high proportion of
      avoidable morbidity and premature mortality in people of South Asian origin
      living in the UK. This review examines available evidence as to why this might be
      and what can be done to address the problems. The sources for data were a Medline
      search by MeSH terms, free text and key authors by name, and relevant references,
      searched by hand, from all review articles in the AIM journals, up to April 1996.
      Most trials identified were epidemiological surveys. The high instance of
      diabetes and some of its complications do not have a single explanation. The
      early incidence of diabetes and its link with coronary heart disease may be
      partially explained by the central adiposity-insulin resistance syndrome.
      Predisposition to this is probably largely genetic but exacerbated by other
      factors such as diet, immune-inflammatory changes, and physical activity levels.
      There is less evidence to support conventional dietary risk factors and some for
      potentially deleterious effects of traditional Western dietary advice in this
      population. The impact of the genetic and environmental influences is exacerbated
      by suboptimal use of health services. The contribution of economic deprivation to
      the poor outcome of diabetes in these patients may be substantial. There is a
      considerable impact of psychosocial stress on morbidity, supporting the view that
      a narrow biomedical model will neither fully explain the problem nor provide
      solutions. To be successful, strategies for the secondary prevention of diabetes
      complications in British South Asians need to incorporate a number of paradigms:
      genetic, physiological, psychological, anthropological, and sociological.
      Recommendations for a multidimensional approach to this important clinical issue
      are proposed.

PMID- 9017349
TI  - The effect of intravenous lactate on cerebral function during hypoglycaemia.
AB  - Any factor which protects the brain against hypoglycaemia induced cerebral
      dysfunction could have important therapeutic implications for intensive insulin
      therapy. This study tested the hypothesis that intravenous lactate protects
      cerebral function during hypoglycaemia. Four choice reaction time, Auditory Brain
      Stem Response (ABR), and P300 latency were used as measures of cerebral function.
      Nine healthy volunteers (six female) underwent two stepped hyperinsulinaemic
      clamps at least 4 weeks apart, achieving blood glucose levels of 4.5, 3.3, and
      2.5 mmol l-1. On one occasion 40 mumol kg-1 min-1 sodium lactate was infused, and
      on the other, normal saline. Cerebral function tests were measured at each
      glucose level. At 3.3 mmol l-1, there was a significant slowing of four choice
      reaction time with saline (p < 0.02) but not with lactate; no changes in P300
      latency or ABR occurred on either occasion. At 2.5 mmol l-1 results from all
      three tests deteriorated significantly during saline infusion (p < 0.001 reaction
      time, p < 0.02 ABR and p < 0.05 P300), but not lactate. Lactate infusion was
      associated with a reduction in noradrenaline (p < 0.05), adrenaline (p < 0.05),
      and growth hormone (p < 0.02) responses at a glucose of 2.5 mmol l-1. These
      results support the hypothesis that intravenous lactate protects cerebral
      function during hypoglycaemia.

PMID- 9017350
TI  - Impaired leucocyte functions in diabetic patients.
AB  - This study evaluates polymorphonuclear neutrophil (PMN) cell performance in 61
      diabetic patients free of infection (40 Type 1, 21 Type 2), using tests that
      explore all the functional steps of PMN: (1) adherence: expression of adhesion
      molecules, CD 11a, CD 11b, CD 11c; nylon fiber adherence test; (2) chemotaxis
      under agarose towards the bacterial oligopeptide FMLP and complement fractions,
      used as attracting agents; (3) phagocytosis of opsonized latex microbeads; (4)
      bactericidal activity: chemiluminescence assessment of the oxidative killing
      potential before and after stimulation by opsonized zymosan and PMA; nitroblue
      tetrazolium reduction test. Results were analysed according to potentially
      influential factors: metabolic control (HbA1C, glycaemia), age of patient, type
      of diabetes, disease duration, and existence of vascular complications. PMN
      chemotaxis was significantly lower in patients than in healthy controls (p <
      0.001) and associated with spontaneous adherence and increased expression of
      adhesion molecules (CD 11b, CD 11c). The increased response to chemiluminescence
      reflects spontaneous activation of PMN cells and increased free radical
      production; after stimulation, response was lower than in controls. The type of
      diabetes, the age of patients, HbA1C level and disease duration did not affect
      the responses. Chemotaxis and chemiluminescence were further reduced in patients
      with vascular complications and hyperglycaemia. We conclude that all steps of PMN
      functioning are altered in diabetic patients, which may increase the risk of
      vascular complications and infectious episodes.

PMID- 9017351
TI  - Parental history of diabetes in an insulin-treated diabetes registry.
AB  - To confirm observations of an excess maternal transmission of Type 2 (non-insulin
      dependent) diabetes mellitus in a setting which minimizes potential biases and
      confounders, we explored the patterns of maternal and paternal diabetes in a
      cohort (n = 1775) of subjects with insulin-treated diabetes mellitus (ITDM) in
      Tasmania, Australia. In order to identify individuals with Type 1 diabetes or
      insulin-treated Type 2 diabetes, cases were classified into groups based on their
      age at diagnosis and subsequent time to commencement of insulin. Individuals
      initially diagnosed younger than age 30 (predominantly Type 1 diabetes cases)
      reported a similar percentage of mothers and fathers with diabetes, but
      individuals diagnosed at age 30 or older (predominantly insulin-treated Type 2
      diabetes) reported a maternal excess of diabetes. Having an elevated body mass
      index was associated with a higher frequency of maternal diabetes, but not of
      paternal diabetes. Because both childhood-onset Type 1 diabetes and adult-onset
      insulin-treated Type 2 diabetes cases were subject to the same potential study
      biases, these results offer support for an excess maternal role in Type 2
      diabetes transmission.

PMID- 9017352
TI  - UKPDS 21: low prevalence of the mitochondrial transfer RNA gene (tRNA(Leu(UUR)))
      mutation at position 3243bp in UK Caucasian type 2 diabetic patients.
AB  - Some patients with Type 2 (non-insulin-dependent) diabetes mellitus possess a
      mitochondrial mutation in the tRNA(Leu(UUR)) gene at position 3243 bp. These
      subjects show a maternal mode of inheritance and often have hearing defects. In
      French and Japanese populations, this mutation may be present in 1-3% of subjects
      with a family history of diabetes. We assessed the prevalence of this mutation in
      newly diagnosed diabetic subjects in the UK white Caucasian population. The 3243
      bp mutation was not detected in 500 randomly selected Type 2 diabetic subjects,
      50 gestational diabetic subjects, and members of a MODY pedigree. Two of 748
      (0.27%) Type 2 diabetic subjects with a family history of diabetes were found to
      possess the mutation. These subjects had an early age of diagnosis (M 38 years; F
      36 years) and were non-obese. The male patient showed evidence of markedly
      impaired beta-cell function and deafness, while the female was not deaf, had
      approximately 50% of normal pancreatic function and responded well to diet. The
      mutation in the tRNA(Leu(UUR)) gene probably occurs in only approximately 0.1
      0.2% of white Caucasian Type 2 diabetic patients in the UK.

PMID- 9017353
TI  - Healing rates of diabetic foot ulcers associated with midfoot fracture due to
      Charcot's arthropathy.
AB  - The aim of this study is to compare the effectiveness of total contact casts
      based on wound location in groups of patients with diabetes mellitus with
      neuropathic ulcerations under the forefoot and patients with midfoot ulcerations
      associated with acute Charcot's arthropathy. Twenty-five consecutive diabetic
      patients with Meggitt-Wagner grade I neuropathic foot ulceration (NU) and 22
      consecutive diabetic patients with neuropathic ulceration and acute Charcot's
      arthropathy (CU) were selected for study. Larger wounds took longer to heal in
      both the CU (p < 0.0001) and NU groups (p < 0.0001). Duration of ulcer prior to
      treatment also was significantly associated with increased healing time in both
      groups (p = 0.008 NU, p = 0.03 CU). The CU group had larger wounds (10.3 +/- 4.6
      vs 7.7 +/- 4.0 cm2, p = 0.04) but took significantly less time to heal (28.4 +/-
      13.0 vs 38.8 +/- 21.3 days, p = 0.04) than did subjects with neuropathic
      ulcerations only. The NU group had their ulcers present for a significantly
      longer period of time prior to contact casting (88.5 +/- 98.3 vs 17.7 +/- 12.9
      days, p = 0.001). In this study, subjects with ulcerations secondary to acute
      Charcot fractures healed more rapidly than in previous reports with healing times
      of forefoot neuropathic ulcers similar to previous studies. Every patient's ulcer
      healed. There were no cast-related ulcerations, infections, or hospitalizations.
      Concerns regarding the safety of total contact casts to treat well-vascularized
      superficial forefoot and midfoot plantar wounds appear to be unfounded.

PMID- 9017354
TI  - Factors associated with diabetic foot ulceration in Thailand: a case-control
      study.
AB  - A case-control study was conducted to determine factors involved in foot
      ulceration in Thai non-insulin-dependent (Type 2) diabetic patients. Fifty-five
      patients with foot ulcers (42 females and 13 males) and 110 patients without foot
      ulcers (83 females and 27 males) were evaluated for 26 factors possibly
      associated with foot ulceration. The results showed that diabetic patients with
      foot ulcers had significantly lower diabetic knowledge and foot-care practice
      scores; poorer glycaemic control, renal function, and visual function, and higher
      prevalence of retinopathy and peripheral neuropathy than diabetic patients
      without foot ulcers, whereas there were no differences in peripheral vascular
      status between both groups, each having a low prevalence. Multiple logistic
      regression analyses indicated that the risk of developing foot ulcers was
      associated with only three factors which were peripheral nerve status as
      determined by somatosensory evoked potentials (OR = 1.67; 95% CI 0.31 -8.97),
      visual acuity (OR = 0.223 per unit decrease in decimal visual acuity; 95% CI =
      0.005, 0.39) and fasting plasma glucose level (OR = 1.01 per mmol l-1 increase;
      95% CI = 1.00, 1.02). We conclude that peripheral neuropathy, visual impairment,
      and poor glycaemic control, but not peripheral vascular insufficiency, are the
      major independent risk factors associated with foot ulceration in Thai diabetic
      patients.

PMID- 9017355
TI  - Partial restoration of scintigraphically assessed cardiac sympathetic denervation
      in newly diagnosed patients with insulin-dependent (type 1) diabetes mellitus at
      one-year follow-up.
AB  - Diabetic neuropathy is thought to comprise a reversible metabolic and an
      irreversible structural component of neuronal abnormality. To investigate whether
      the cardiac sympathetic denervation recently described in newly diagnosed, but
      metabolically stabilized, diabetic patients without myocardial perfusion
      abnormalities reflects transient or permanent sympathetic abnormalities, 123-I
      metaiodobenzylguanidine (123-I-MIBG) scintigraphy was performed in 16 patients
      with insulin-dependent (Type 1) diabetes mellitus (IDDM) 1 year after initial
      assessment and diagnosis. All patients had been treated with an intensified
      insulin therapy for 1 year. HbA1c had fallen from 11.5 +/- 2.0% to 6.3 +/- 0.9%
      (p < 0.001). The global myocardial 123-I-MIBG uptake (score 1-6) had improved in
      7 patients at 1 year, remained unchanged in 7, and deteriorated in 2 patients.
      Regionally, the myocardial uptake score of the posterior and septal regions had
      improved significantly (p < 0.01, p = 0.02) with a mean uptake score in the
      groups of 3.8 +/- 1.1 and 3.4 +/- 1.2 at diagnosis versus 2.6 +/- 0.5 and 2.5 +/-
      0.9 at 1 year. Myocardial uptake scores of the anterior, lateral, and apical
      regions had also improved in 7, 6, and 9 patients, but the mean changes of these
      scores did not reach significance. The study demonstrates that scintigraphically
      assessed cardiac sympathetic denervation in newly diagnosed, but metabolically
      stabilized, IDDM patients is partially reversed with improved metabolic control
      after 1 year of intensified insulin therapy. We suggest that even in the early
      stage of IDDM, cardiac sympathetic dysfunction is composed of reversible and
      irreversible neuronal abnormalities.

PMID- 9017356
TI  - Time-action profile of inhaled insulin.
AB  - We compared the pharmacodynamics of insulin after inhalation of 99 U
      microcrystalline solid insulin and subcutaneous injection of 10 U regular insulin
      and intravenous injection of 5 U regular insulin. The time-action profiles of the
      three insulin administrations were studied in 11 healthy volunteers using the
      euglycaemic glucose clamp technique. The insulins were administered to each
      volunteer on three separate occasions in random order. Onset of action, assessed
      as glucose infusion rate, after insulin inhalation was substantially more rapid
      than after subcutaneous injection and half-maximal action was reached earlier (31
      +/- 17 vs 54 +/- 12 min; p < 0.001). Maximal metabolic response was reached
      earlier after insulin inhalation in comparison to subcutaneous injection (108 +/-
      49 vs 147 +/- 53 min; p < 0.001). The maximal glucose infusion rate after
      inhalation of insulin was lower than after subcutaneous insulin injection (6.2
      +/2- 2.4 vs 9.1 +/- 2.5 mg kg-1 min-1; p < 0.001). The glucose infusion rates in
      the first 60 min after inhalation were significantly greater than after insulin
      injection (area under the glucose infusion rate curve: 0.23 +/- 0.12 vs 0.13 +/-
      0.08 g kg-1 60 min-1; p < 0.001). However, the total metabolic effect after
      inhalation was significantly lower than after insulin injection (1.44 +/- 0.68 vs
      1.90 +/- 0.47 g kg-1 360 min-1; p < 0.001). Relative effectiveness of inhaled
      insulin calculated with regard to the data from the intravenous insulin
      application was 9.5 +/- 4.1% and of the subcutaneous insulin application was 7.6
      +/- 2.9%. With its rapid onset of action, inhaled insulin might have potential
      for clinical use.

PMID- 9017357
TI  - Social relationships among young adults with insulin-dependent diabetes mellitus:
      ten-year follow-up of an onset cohort.
AB  - Past cross-sectional studies have suggested that young adults with insulin
      dependent (Type 1) diabetes mellitus (IDDM) may experience problems in their
      close peer relationships. For 10 years, we have followed an onset cohort of
      children and adolescents with IDDM (n = 57) and an age-matched group who were
      originally recruited after an acute illness, accident, or injury (n = 54). Now
      aged 19-26 years, these two groups were compared in terms of their friendship
      patterns, dating and love experiences, and sense of loneliness. All subjects in
      both groups had at least one friend. However, the IDDM group reported fewer
      friendships overall. The difference was accounted for by the number of less
      intimate friends. The two groups had similar frequencies of current romantic
      partners (IDDM = 63%; comparison group = 64%). While dating attitude and dating
      assertiveness did not differ between groups, some differences were found in terms
      of experiences of a primary love relationship. IDDM patients experienced less
      trust and sense of intimate friendship in these love relationships. No
      differences in loneliness were found. The preponderance of our findings indicate
      that the two groups had similar patterns and experiences of close peer
      relationships. Thus, the study does not suggest that IDDM leads to serious
      problems in forming social relationships for these patients during the transition
      to young adulthood. On the other hand, the IDDM patients' lower level of trust
      and intimacy within love relationships are consistent with other findings from
      this study suggesting specific areas of lowered self-worth that appear in social
      relationships.

PMID- 9017358
TI  - Remission of non-insulin-dependent diabetes mellitus following resection of a
      parathyroid adenoma.
AB  - A 56-year-old woman presented with diabetes mellitus and primary
      hyperparathyroidism simultaneously. Initial random blood glucose was recorded at
      20.8 mmol l-1, serum calcium was 3.07 mmol l-1 (normal range 2.10-2.55 mmol l-1),
      and plasma parathyroid hormone estimation by intact assay was 110 ng l-1 (normal
      range 10-65 ng l-1). Initial glycated haemoglobin was 9.4% (non-diabetic range <
      7.5%). Left lower parathyroidectomy was carried out and pathology confirmed the
      presence of a chief cell adenoma. The gland measured 10 x 5 x 5 mm. Following
      parathyroidectomy serum calcium normalized, glucose tolerance improved, and a
      subsequent 75 g oral glucose tolerance test was normal. The patient weighted 80
      kg at presentation but the post-operative weight had risen to 81.5 kg. The most
      recent glycated haemoglobin was 4.6%. Primary hyperparathyroidism may have a
      reversible effect on glucose tolerance.

PMID- 9017359
TI  - Is impaired baroreflex sensitivity a predictor or cause of sudden death in
      insulin-dependent diabetes mellitus?
AB  - Sudden death at night is known to occur in young patients with insulin-dependent
      (Type 1) diabetes mellitus (IDDM) but the aetiology is uncertain. A cardiac
      arrhythmia has been postulated, but there has been little evidence to support
      this. We present the case of a 31-year-old man with IDDM of 17 years duration,
      who died suddenly while asleep. Over preceding months, he had had strict
      glycaemic control (HbA1 8.9%), normal 24 h blood pressure (mean 131 +/- 2.1/76 +/
      2.2 mmHg), no evidence of microangiopathy or endothelial dysfunction and normal
      standard clinical tests of autonomic function. An electrocardiogram was similarly
      unremarkable, with a QTc interval of 0.414 s, and an echocardiogram had
      demonstrated normal left ventricular mass index (96.4 g m-2). However, there was
      no nocturnal dip in heart rate (daytime 74 +/- 2.7, and nocturnal 68 +/- 1.6
      beats min-1), and he had grossly impaired baroreflex sensitivity during Phase 4
      of the valsalva manoeuvre (0.5 ms mmHg-1), with power spectral analysis studies
      suggesting an abnormality of parasympathetic function. The coroner's autopsy
      demonstrated no structural abnormalities. We hypothesize that abnormal baroreflex
      sensitivity could either predict a risk of or account for some of the unexplained
      deaths in IDDM, in that relative overactivity of the sympathetic nervous system
      could cause ventricular arrhythmias.

PMID- 9017360
TI  - Aberrant results due to incorrect use of the Bayer Glucometer 4 meter.

PMID- 9017361
TI  - A synthetic form of tracheal antimicrobial peptide has both bactericidal and
      antifungal activities.
AB  - We have chemically synthesized tracheal antimicrobial peptide (TAP) with 38 amino
      acids and examined efficacy of the peptide on various organisms. The synthetic
      peptide showed potent bactericidal effect on both gram positive and negative
      bacteria. The action of bactericidal effect was relatively quick and 99.9% of E.
      coli cells were killed within 90 minutes at a concentration of 2.5 micrograms/ml
      of TAP. The peptide also showed antifungal activity against both mycelia
      (Aspergillus fumigatus) and yeast (Candida albicans) forms of fungi. Our domain
      analysis with a series of synthetic peptides of various lengths indicates that 17
      amino acid residues of the C-terminal end is the minimum functional domain of the
      bactericidal activity.

PMID- 9017362
TI  - Effects of adjuvant, dose and carrier pre-sensitisation on the immunisation
      efficacy of a GnRH analogue.
AB  - A GnRH-neutralising vaccine, with potential applications in the treatment of
      human sex hormone-dependent disorders, was developed by conjugating GnRH-glycys
      to tetanus toxoid. An evaluation of adjuvant, dose and carrier pre-sensitisation
      was made. Male rats immunised with the conjugate, adsorbed onto alum, showed
      higher anti-GnRH antibody levels and suppressed testosterone concentrations,
      compared with animals immunised without adjuvant. Conjugate administration in a
      four injection regime proved to be the most effective in disrupting fertility, as
      assessed by the degree of lowered testosterone levels and gonadal atrophy. Pre
      sensitisation with tetanus toxoid had an initial marked effect on immunisation,
      observed following 2 drug doses; the pre-sensitised animals showed a lower
      antibody response to the conjugate than did the non-primed animals. However, as
      the number of drug doses increased to 4, there was no significant difference
      between the primed and non-primed animals.

PMID- 9017363
TI  - Three-dimensional molecular models of the hMC1R melanocortin receptor: complexes
      with melanotropin peptide agonists.
AB  - Three-dimensional molecular models of the human melanocortin receptor (hMC1R)
      have been developed based upon the electron cryo-microscopic structure of
      bacteriorhodopsin and the electron density footprint of bovine rhodopsin. alpha
      Melanocyte-stimulating hormone, Ac-Ser-Tyr-Ser-Met4-Glu-His-Phe7-Arg-Trp-Gly-Lys
      Pro-Val-NH2 (alpha-MSH, alpha-melanotropin), and the superpotent, prolonged
      acting agonists, Ac-Ser-Tyr-Ser-Nle4-Glu-His-DPhe7-Arg-Trp-Gly-Lys-Pro-Val-NH2
      (NDP-MSH) and Ac-Nle4-c[Asp5-His6-DPhe7-Arg8-Trp9-Lys10]-NH2 (MTII), have been
      modeled into the proposed binding sites with specific ligand-receptor
      interactions identified. The melanotropin sidechain pharmacophores, DPhe7 and
      Trp9, are proposed to interact with a hydrophobic network of receptor aromatic
      residues in transmembrane regions 4, 5, 6, and 7. In addition, a hydrophilic
      network involving the ligand Arg8 and polar receptor residues located in
      transmembrane regions 2 and 3 were identified. Biological studies on alpha-MSH,
      NDP-MSH, MTII, and related peptides have been correlated with the proposed hMC1R
      model in terms of agonism, affinity, and prolongation. Finally, limited MC1R
      mutagenesis studies comparing alpha-MSH and NDP-MSH are interpreted within the
      context of the proposed hMC1R models.

PMID- 9017364
TI  - Molecular simulation of the folding patterns of the omega-loop (Tyr181 to Tyr188)
      of HIV-1 reverse transcriptase.
AB  - A large, highly hydrophilic and constrained omega-loop was dissected from the
      allosteric area of HIV-1 reverse transcriptase (segment Tyr181 to Tyr188). The
      loop contains two amino acids (Asp185, Asp186) of the catalytic aspartyl triad
      (Asp110, Asp185, Asp186) and two amino acids (Tyr181, Tyr188) of the
      nonnucleoside RT inhibitor (NNRTI) binding sites. Hydrogen-bonding forces between
      the two folded peptide chains play the greatest role in holding the two chains
      together and in specifying the folding patterns. The treatment of solvents as
      dielectric continuums surrounding the AMBER force field model has shown changes
      in conformation but these changes were not dramatically because the omega-loop
      shape was completely maintained.

PMID- 9017365
TI  - A hydrophilic omega-loop (Tyr181 to Tyr188) in the nonsubstrate binding area of
      HIV-1 reverse transcriptase.
AB  - Using the molecular "cloud" of the HIV-1 reverse transcriptase (RT) as starting
      point, the peptide backbone of the polymerase subunit was visualized by molecular
      modelling. Then, the two subregions 98-106 and 179-190 of the allosteric area
      were "isolated". From the latter subregion, the Tyr181 to Tyr188 segment
      containing two amino acids (Asp185, Asp186) of the catalytic aspartyl triad and
      two amino acids (Tyr181, Tyr188) of the nonnucleoside RT inhibitor (NNRTI)
      binding sites, was excised. It was shown that the segment has a omega-like loop
      configuration which is highly hydrophilic. The two phenolic side chains of Tyr181
      and Tyr188 represent the lipophilic "horizontal axes" of the omega-loop shape.
      The relative rigidity of the omega-loop is mainly based on a hydrogen bond
      between the peptide CO of Tyr181 and the peptide NH of Tyr188. Solvation in water
      increases the number of intramolecular hydrogen bonds. Therefore, desolvation is
      one of the conditions of binding with NNRTIs. Site-directed mutagenesis affects
      the hydrophilicity of the omega-loop while steric features are less influenced.

PMID- 9017366
TI  - Evidence of a butterfly-like configuration of structurally diverse allosteric
      inhibitors of the HIV-1 reverse transcriptase.
AB  - Although many physicochemical properties of chemically diverse nonnucleoside
      inhibitors of HIV-1 reverse transcriptase (NNRTIs) differ, there is a common
      three-dimensional feature. This shape is a rigid butterfly-like configuration
      which fits well into a sizable internal cavity of the allosteric area of the
      enzyme. The number of amino acids of the allosteric receptor sites that
      contribute to NNRTIs binding correlates with the degree of the butterfly-like
      shape. It seems that molecular rigidity of the butterfly-like shape, the drug
      affinity and the probability of resistance development are closely related.

PMID- 9017382
TI  - The 1996 Thomas Hunt Morgan Medal Franklin W. Stahl.

PMID- 9017383
TI  - The 1996 Genetics Society of America Medal Elliot Meyerowitz.

PMID- 9017384
TI  - Plants and the logic of development.

PMID- 9017385
TI  - Invasions of P elements.

PMID- 9017386
TI  - A Salmonella phage-P22 mutant defective in abortive transduction.
AB  - In the course of a lytic infection the Salmonella phage P22 occasionally
      encapsulates bacterial DNA instead of phage DNA. Thus, phage lysates include two
      classes of viral particles. Phage particles carrying bacterial DNA are referred
      to as transducing particles and deliver this DNA to a host as efficiently as
      particles carrying phase DNA. Once injected, the transduced DNA can either
      recombine with the recipient chromosome to form a "complete" transductant, or it
      can establish itself as an expressible, nonreplicating genetic element and form
      an "abortive" transductant. In this work, we describe a P22-phage mutant with
      reduced ability to form abortive transductants. The mutation responsible for this
      phenotype, called tdx-1, was found as one of two mutations contributing to the
      high-transducing pheno-type of the P22-mutant HT12/4. In addition, the tdx-1
      mutation is lethal when combined with an erf am mutation. The tdx-1 mutation has
      been mapped to a region of the P22 genome that encodes several injected proteins
      and may involve more than one mutant locus. The phenotypes of the tdx-l mutation
      suggest that the Tdx protein(s) normally assist in the circularization of the P22
      genome and also contribute to the formation of DNA circles thought to be required
      for abortive transduction.

PMID- 9017387
TI  - Highly mismatched molecules resembling recombination intermediates efficiently
      transform mismatch repair proficient Escherichia coli.
AB  - The ability of related DNAs to undergo recombination decreases with increased
      sequence divergence. Mismatch repair has been proposed to be a key factor in
      preventing homeologous recombination; however, the contribution of mismatch
      repair is not universal. Although mismatch repair has been proposed to act by
      preventing strand exchange and/or inactivating multiply mismatched
      heteroduplexes, there has been no systematic study to determine at what step(s)
      in recombination mismatch repair acts in vivo. Since heteroduplex is a commonly
      proposed intermediate in many models of recombination, we have investigated the
      consequences of mismatch repair on plasmids that are multiply mismatched in
      heteroduplex structures that are similar to those that might arise during
      recombination. Plasmids containing multiply mismatched regions were transformed
      into wild-type and Mut+ Escherichia coli mutants. There was only a 30-40%
      reduction in transformation of Mut+ as compared to mutS and mutL strains for DNAs
      containing an 18% mismatched heteroduplex. The products obtained from mutS hosts
      differed from those obtained from Mut+ hosts in that there were many more
      colonies containing mixtures of two plasmids, due to survival of both strands of
      the heteroduplex. There were nearly 10 times more recombinants obtained from the
      mutS as compared to the wild-type host. Based on these results and those from
      other studies with E. coli and yeast, we propose that the prevention of
      recombination between highly diverged DNAs may be at a step earlier than
      heteroduplex formation.

PMID- 9017388
TI  - On the specificity of adaptive mutations.
AB  - Adaptive mutations are mutations that occur in nondividing or slowly dividing
      cells during prolonged nonlethal selection, and that appear to be specific to the
      challenge of the selection in the sense that the only mutations that arise are
      those that provide a growth advantage to the cell. The issue of the specificity
      has been controversial because it violates our most basic assumptions about the
      randomness of mutations with respect to their effect on the cell. Although a
      variety of experiments in several systems in both bacteria and yeast have claimed
      to demonstrate that specificity, those experiments have been subjected to a
      variety of technical criticisms suggesting that the specificity may not be real.
      Here I use the ebg system to provide evidence that when selection is applied to
      one specific nucleotide site within a gene, mutation occurs at that site but not
      at an alternative and equally mutable site within the same gene.

PMID- 9017389
TI  - RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces
      cerevisiae in response to DNA damage.
AB  - We have previously shown that a checkpoint dependent on MEC1 and RAD53 slows the
      rate of S phase progression in Saccharomyces cerevisiae in response to alkylation
      damage. Whereas wild-type cells exhibit a slow S phase in response to damage,
      mec1-1 and rad53 mutants replicate rapidly in the presence or absence of DNA
      damage. In this report, we show that other genes (RAD9, RAD17, RAD24) involved in
      the DNA damage checkpoint pathway also play a role in regulating S phase in
      response to DNA damage. Furthermore, RAD9, RAD17, and RAD24 fall into two groups
      with respect to both sensitivity to alkylation and regulation of S phase. We also
      demonstrate that the more dramatic defect in S phase regulation in the mec1-1 and
      rad53 mutants is epistatic to a less severe defect seen in rad9 delta, rad 17
      delta, and rad24 delta. Furthermore, the triple rad9 delta rad17 delta rad24
      delta mutant also has a less severe defect than mec1-1 or rad53 mutants. Finally,
      we demonstrate the specificity of this phenotype by showing that the DNA repair
      and/or checkpoint mutants mgt1 delta, mag1 delta, apn1 delta, rev3 delta, rad18
      delta, rad16 delta, dun1-delta 100, sad4-1, tel1 delta, rad26 delta, rad51 delta,
      rad52-1, rad54 delta, rad14 delta, rad1 delta, pol30-46, pol30-52, mad3 delta,
      pds1 delta/esp2 delta, pms1 delta, mlh1 delta, and msh2 delta are all proficient
      at S phase regulation, even though some of these mutations confer sensitivity to
      alkylation.

PMID- 9017390
TI  - Proteolytic activation of Rim1p, a positive regulator of yeast sporulation and
      invasive growth.
AB  - In the yeast Saccharomyces cerevisiae, rim1, 8, 9, or 13 mutations cause four
      phenotypes: poor growth at low temperature, altered colony morphology,
      inefficient sporulation due to reduced expression of the meiotic activator IME1,
      and, as shown here, defective invasive growth. In this report, we have determined
      the relationship between RIM1 and the other genes, RIM8, 9, and 13, in this
      group. We have analyzed production of epitope-tagged Rim1p derivatives with HA
      epitopes at the N-terminus or in the middle of the protein. These Rim1p
      derivatives exist primarily as a small form (90 kD for Rim1-HA2p) in wild-type
      cells and as a large form (98 kD for Rim1-HA2p) in rim8, 9, and 13 mutants. We
      have also analyzed production of beta-galactosidase in strains that express a
      RIM1-lacZ fusion gene. beta-galactosidase exists primarily as a approximately 130
      kD form in wild-type cells and as a approximately 190 kD form in rim9 mutants.
      These results indicate that Rim1p undergoes C-terminal proteolytic cleavage, and
      that rim8, 9, and 13 mutations block cleavage. Expression of a Rim1p C-terminal
      deletion derivative suppresses rim8, 9, and 13 mutations. Thus the phenotypes of
      rim8, 9, and 13 mutants arise from the defect in Rim1p C-terminal cleavage.
      Cleavage of Rim1p, like that of its Aspergillus nidulans homologue PacC, is
      stimulated under alkaline growth conditions. Therefore, Rim1p, PacC and their
      respective processing pathways may represent a conserved signal transduction
      pathway.

PMID- 9017391
TI  - apd1+, a gene required for red pigment formation in ade6 mutants of
      Schizosaccharomyces pombe, encodes an enzyme required for glutathione
      biosynthesis: a role for glutathione and a glutathione-conjugate pump.
AB  - Mutants in the adenine biosynthetic pathway of yeasts (ade1 and ade2 of
      Saccharomyces cerevisiae, ade6 and ade7 of Schizosaccharomyces pombe) accumulate
      an intense red pigment in their vacuoles when grown under adenine-limiting
      conditions. The precise events that determine the formation of the pigment are
      however, still unknown. We have begun a genetic investigation into the nature and
      cause of pigmentation of ade6 mutants of S. pombe and have discovered that one of
      these pigmentation defective mutants, apd1 (adenine pigmentation defective), is a
      strict glutathione auxotroph. The gene apd1+ was found to encode the first enzyme
      in glutathione biosynthesis, gamma-glutamylcysteine synthetase, gcs1+. This gene
      when expressed in the mutant could confer both glutathione prototrophy and the
      characteristic red pigmentation, and disruption of the gene led to a loss in both
      phenotypes. Supplementation of glutathione in the medium, however, could only
      restore growth but not the pigmentation because the cells were unable to achieve
      sufficient intracellular levels of glutathione. Disruption of the second enzyme
      in glutathione biosynthesis, glutathione synthetase gsh2+, also led to
      glutathione auxotrophy, but only a partial defect in pigment formation. A
      reevaluation of the major amino acids previously reported to be present in the
      pigment indicated that the pigment is probably a glutathione conjugate. The
      ability of vanadate to inhibit pigment formation indicated that the conjugate was
      transported into the vacuole through a glutathione-conjugate pump. This was
      further confirmed using strains of S. cerevisiae bearing disruptions in the
      recently identified glutathione-conjugate pump, YCF1, where a significant
      reduction in pigment formation was observed. The pump of S. pombe is distinct
      from the previously identified vacuolar pump, hmt1p, for transporting cadystin
      peptides into vacuoles of S. pombe.

PMID- 9017392
TI  - The Swi5 transcription factor of Saccharomyces cerevisiae has a role in exit from
      mitosis through induction of the cdk-inhibitor Sic1 in telophase.
AB  - Deactivation of the B cyclin kinase (Cdc28/Clb) drives the telophase to G1 cell
      cycle transition. Here we investigate one of the control pathways than
      contributes to kinase deactivation, involving the cell cycle-regulated production
      of the cdk inhibition Sic1. We show that the cell cycle timing of SIC1 expression
      depends on the transcription factor Swi5, and that Swi5-dependent SIC1 expression
      begins during telophase. In contrast to Swi5, the related transcription factor
      Ace2, which can also induce SIC1 expression, is not active during telophase. The
      functional consequence of Swi5-regulated SIC1 expression in vivo is that both
      sic1 delta and swi5 delta strains have identical mitotic exit-related phenotypes.
      First, both are synthetically lethal with dbj2 delta, resulting in cell cycle
      arrest in telophase. Second, both are hypersensitive to overexpression of the B
      cyclin CLB2. Thus Swi5-dependent activation of the SIC1 gene contributes to the
      deactivation of the B cyclin kinase, and hence exit from mitosis.

PMID- 9017393
TI  - A eubacterial gene conferring spectinomycin resistance on Chlamydomonas
      reinhardtii: integration into the nuclear genome and gene expression.
AB  - We have constructed a dominant selectable marker for nuclear transformation of C.
      reinhardtii, composed of the coding sequence of the eubacterial aadA gene
      (conferring spectinomycin resistance) fused to the 5' and 3' untranslated regions
      of the endogenous RbcS2 gene. Spectinomycin-resistant transformants isolated by
      direct selection (1) contain the chimeric gene(s) stably integrated into the
      nuclear genome, (2) show cosegregation of the resistance phenotype with the
      introduced DNA, and (3) synthesize the expected mRNA and protein. Small
      linearized plasmids appeared to be inserted into the nuclear genome
      preferentially through their ends, with relatively few large deletions and/or
      rearrangements. Multiple copy transformants often integrated concatemers of
      transforming DNA. Our detailed analysis of the complex integration patterns of
      plasmid DNA in C. reinhardtii nuclear transformants should be useful for
      improving the technique of insertional mutagenesis. We also found that the
      spectinomycin-resistance phenotype was unstable in about half of the
      transformants. When maintained under nonselective conditions, neither the aadA
      mRNA nor the AadA protein were detected in these subclones. Moreover, since the
      integrated transforming DNA was not altered or lost expression of the
      RbcS2::aadA::RbcS2 gene(s) appears to be repressed. Measurements of
      transcriptional activity, mRNA accumulation, and mRNA stability suggest that
      expression of this chimeric gene(s) may also be affected by rapid RNA
      degradation, presumably due to defects in mRNA processing and, or nuclear export.
      Thus, both gene silencing and transcript instability, rather than biased codon
      usage, may explain the difficulties encountered in the expression of foreign
      genes in the nuclear genome of Chlamydomonas.

PMID- 9017394
TI  - glp-3 is required for mitosis and meiosis in the Caenorhabditis elegans germ
      line.
AB  - The germ line is the only tissue in Caenorhabditis elegans in which a stem cell
      population continues to divide mitotically throughout life; hence the cell cycles
      of the germ line and the soma are regulated differently. Here we report the
      genetic and phenotypic characterization of the glp-3 gene. In animals homozygous
      for each of five recessive loss-of-function alleles, germ cells in both
      hermaphrodites and males fail to progress through mitosis and meiosis, but
      somatic cells appear to divide normally. Germ cells in animals grown at 15
      degrees appear by DAP1 staining to be uniformly arrested at the G2/M transition
      with < 20 germ cells per gonad on average, suggesting a checkpoint-mediated
      arrest. In contrast, germ cells in mutant animals grown at 25 degrees frequently
      proliferate slowly during adulthood, eventually forming small germ lines with
      several hundred germ cells. Nevertheless, cells in these small germ lines never
      undergo meiosis. Double mutant analysis with mutations in other genes affecting
      germ cell proliferation supports the idea that glp-3 may encode a gene product
      that is required for the mitotic and meiotic cell cycles in the C. elegans germ
      line.

PMID- 9017395
TI  - Interactions of Drosophila Ultrabithorax regulatory regions with native and
      foreign promoters.
AB  - The Ultrabithorax (Ubx) gene of the Drosophila bithorax complex is required to
      specify parasegments 5 and 6. Two P-element "enhancer traps" have been recovered
      within the locus that contain the bacterial lacZ gene under the control of the P
      element promoter. The P insertion that is closer to the Ubx promoter expresses
      lacZ in a pattern similar to that of the normal Ubx gene, but also in parasegment
      4 during embryonic development. Two deletions have been recovered that remove the
      normal Ubx promoter plus several kilobases on either side, but retain the lacZ
      reporter gene. The lacZ patterns from the deletion derivatives closely match the
      normal pattern of Ubx expression in late embryos and imaginal discs. The lacZ
      genes in the deletion derivatives are also negatively regulated by Ubx and
      activated in trans by Contrabithorax mutations, again like the normal Ubx gene.
      Thus, the deleted regions, including several kilobases around the Ubx promoter,
      are not required for long range interactions with Ubx regulatory regions. The
      deletion derivatives also stimulate transvection, a pairing-dependent interaction
      with the Ubx promoter on the homologous chromosome.

PMID- 9017396
TI  - Quantitative genetics of sperm precedence in Drosophila melanogaster.
AB  - To assess the genetic basis of sperm competition under conditions in which it
      occurs, I estimated additive, dominance, homozygous and environmental variance
      components, the effects of inbreeding, and the weighted average dominance of
      segregating alleles for two measures of sperm precedence in a large, outbred
      laboratory population. Both first and second male precedence show significant
      decline on inbreeding. Second male precedence demonstrates significant dominance
      variance and homozygous genetic variance, but the additive variance is low and
      not significantly different from zero. For first male precedence, the variance
      among homozygous lines is again significant, and dominance variance is larger
      than the additive variance, but is not statistically significant. In contrast,
      male mating success and other fitness components in Drosophila generally exhibit
      significant additive variance and little or no dominance variance. Other recent
      experiments have shown significant genotypic variation for sperm precedence and
      have associated it with allelic variants of accessory-gland proteins. The
      contrast between sperm precedence and other male fitness traits in the structure
      of quantitative genetic variation suggests that different mechanisms may be
      responsible for the maintenance of variation in these traits. The pattern of
      genetic variation and inbreeding decline shown in this experiment suggests that
      one or a few genes with major effects on sperm precedence may be segregating in
      this population.

PMID- 9017397
TI  - Characterization of functional domains of the su(Hw) protein that mediate the
      silencing effect of mod(mdg4) mutations.
AB  - The suppressor of Hairy-wing [su(Hw)] protein represses enhancer function in a
      unidirectional fashion: enhancers segregated from the promoter by the su(Hw)
      binding region are rendered inactive. whereas those in the same domain are
      unaffected. In the case of the gypsy-induced y2 allele, the repressive effect of
      su(Hw) is rendered bidirectional in mod(mdg4) mutant flies, and all enhancers of
      the affected gene become inactive. This silencing of enhancer elements might be
      due to exposure of specific domains of su(Hw) when the mod(mdg4) protein is
      absent. Two of three regions of su(Hw) that are located adjacent to the leucine
      zipper motif and are conserved across Drosophila species are necessary for both
      the unidirectional and bidirectional repression of transcription by su(Hw). In
      contrast, two acidic domains that are dispensable for the unidirectional
      repression of enhancer elements are critical for the bidirectional silencing of
      enhancer activity observed in mutants lacking functional mod(mdg4) protein.

PMID- 9017398
TI  - Characterization of maternal and zygotic D-raf proteins: dominant negative
      effects on Torso signal transduction.
AB  - The maternal D-raf serine/threonine kinase acts downstream of Torso (Tor) for
      specification of cell fates at the embryonic termini. D-raf activity is also
      required in other signal transduction pathways and consistent with its
      pleiotropic role, we find accumulation of a 90-kD D-raf protein throughout
      embryonic development. We also characterize the accumulation of maternal D-raf
      proteins in 0-2-hr embryos derived from females with germ cells lacking D-raf
      activity. Accumulation of a 90-kD or truncated mutant D-raf protein is observed
      for some of these embryos, while others lack the maternal D-raf protein. Then to
      determine whether rescue of the Tor pathway is influenced by pools of
      nonfunctional maternal D raf. wild-type D-raf mRNA was injected into embryos that
      inherit maternal stores of inactive 90-kD of truncated D-raf protein. For embryos
      lacking the maternal D-raf protein, a high level of terminal rescue is obtained.
      In contrast, rescue is reduced or not observed for embryos that accumulate mutant
      maternal D-raf proteins. These findings suggest that mutant forms of D-raf may
      deplete the embryo of a positive activator and/or form inactive protein complexes
      that affect rescue of the Tor pathway.

PMID- 9017399
TI  - The mutation masculinizer (man) defines a sex-determining gene with maternal and
      zygotic functions in Musca domestica L.
AB  - In Musca domestica, the primary signal for sex determination is the dominant
      factor M, which is assumed to regulate a postulated female-determining gene F.
      Presence of M prevents expression of F so that male development ensues. In the
      absence of M, F can become active, which dictates the female pathway. The
      existence of F is inferred from FD. a dominant factor that is epistatic to M. We
      describe a new mutation masculinizer, which has all the properties expected for a
      null or strongly hypomorphic allele of F: (1) it maps to the same chromosomal
      location as FD, (2) homozygous man/man animals develop as males, (3) homozygous
      man/man clones generated in man/+ female larvae differentiate male structures,
      (4) man has a sex-determining maternal effect. About a third of the morphological
      males synthesize yolk proteins, which indicates that they are intersexual in
      internal structures. The maternal effect of man is complete in offspring that
      derive from homozygous man/man pole cells transplanted into female hosts. In this
      case, all man/+ progeny become fertile males that do not produce yolk proteins A
      sex-determining maternal effect has previously been demonstrated for FD. Like F,
      maternal man' is needed for zygotic man' to become active, providing further
      evidence that man is a loss-of-function allele of F.

PMID- 9017400
TI  - The evolution of mammalian olfactory receptor genes.
AB  - We performed a comparative study of four subfamilies of olfactory receptor genes
      first identified in the dog to assess changes in the gene family during mammalian
      evolution, and to begin linking the dog genetic map to that of humans. The human
      subfamilies were localized to chromosomes 7, 11, and 19. The two subfamilies that
      were tightly linked in the dog genome were also tightly linked in the human
      genome. The four subfamilies were compared in human (primate), horse
      (perissodactyl), and a variety of artiodactyls and carnivores. Some changes in
      gene number were detected, but overall subfamily size appeared to have been
      established before the divergence of these mammals 60-100 million years ago.

PMID- 9017401
TI  - An allelic series of blue fluorescent trp1 mutants of Arabidopsis thaliana.
AB  - Nine blue fluorescent mutants of the flowering plant Arabidopsis thaliana were
      isolated by genetic selections and fluorescence screens. Each was shown to
      contain a recessive allele of trp1, a previously described locus that encodes the
      tryptophan biosynthetic enzyme phosphoribosylanthranilate transferase (PAT,
      called trpD in bacteria). The trp1 mutants consist of two groups, tryptophan
      auxotrophs and prototrophs, that differ significantly in growth rate, morphology,
      and fertility. The trp1 alleles cause plants to accumulate varying amounts of
      blue fluorescent anthranilate compounds, and only the two least severely affected
      of the prototrophs have any detectable PAT enzyme activity. All four of the trp1
      mutations that were sequenced are G to A or C to T transitions that cause an
      amino acid change, but in only three of these is the affected residue
      phylogenetically conserved. There is an unusually high degree of sequence
      divergence in the single-copy gene encoding PAT from the wild-type Columbia and
      Landsberg erecta ecotypes of Arabidopsis.

PMID- 9017402
TI  - Microsatellite genetic distances with range constraints: analytic description and
      problems of estimation.
AB  - Statistical properties of the symmetric stepwise-mutation model for
      microsatellite evolution are studied under the assumption that the number of
      repeats is strictly bounded above and below. An exact analytic expression is
      found for the expected products of the frequencies of alleles separated by k
      repeats. This permits characterization of the asymptotic behavior of our
      distances D1 and (delta mu)2 under range constraints. Based on this
      characterization we develop transformations that partially restore linearity when
      allele size is restricted. We show that the appropriate transformation cannot be
      applied in the case of varying mutation rates (beta) and range constraints (R)
      because of statistical difficulties. In the special case of no variation in beta
      and R across loci, however, the transformation simplifies to a usable form and
      results in a distance much more linear with time than distances developed for an
      infinite range. Although analytically incorrect in the case of variation in beta
      and R, the simpler transformation is surprisingly insensitive to variation in
      these parameters, suggesting that it may have considerable utility in
      phylogenetic studies.

PMID- 9017403
TI  - Reinventing the tale.

PMID- 9017404
TI  - On the welfare of possible persons.

PMID- 9017405
TI  - Thin on the details.

PMID- 9017406
TI  - Thin on the details.

PMID- 9017407
TI  - Old World News. In the family's best interests.

PMID- 9017408
TI  - Market meditopia. A glimpse at American health care in 2005.

PMID- 9017409
TI  - In case of emergency: no need for consent.
AB  - The Food and Drug Administration (FDA) is amending its current informed consent
      regulations to permit harmonization of the Department of Health and Human
      Services' (DHHS) policies on emergency research and to reduce confusion on when
      such research can proceed without obtaining an individual subject's informed
      consent. This regulation provides a narrow exception to the requirement for
      obtaining and documenting informed consent from each human subject, or his or her
      legally authorized representative, prior to initiation of an experimental
      intervention. The exception would apply to a limited class of research activities
      involving human subjects who are in need of emergency medical intervention but
      who cannot give informed consent because of their life-threatening medical
      condition, and who do not have a legally authorized person to represent them. FDA
      is taking this action in response to growing concerns that current rules are
      making high quality acute care research activities difficult or impossible to
      carry out at a time when the need for such research is increasingly recognized.

PMID- 9017410
TI  - The European convention on bioethics.
AB  - Nearly fifteen years after the Council of Europe first called for a pan-European
      convention on issues in bioethics to harmonize disparate national regulations, in
      November 1996 the council's Committee of Ministers approved the Convention on
      Human Rights and Biomedicine for formal adoption. The draft convention, released
      in July 1994, provoked strong public, professional, and governmental debate among
      European nations, particularly regarding provisions for biomedical research with
      subjects unable to give informed consent. If ratified, the "bioethics convention"
      will become the first such document to have binding force internationally.

PMID- 9017411
TI  - Retiring the pacemaker.

PMID- 9017412
TI  - Making sausage: The Ninth Circuit's opinion.

PMID- 9017413
TI  - Is it time to abandon brain death?
AB  - Despite its familiarity and widespread acceptance, the concept of "brain death"
      remains incoherent in theory and confused in practice. Moreover, the only purpose
      served by the concept is to facilitate the procurement of transplantable organs.
      By abandoning the concept of brain death and adopting different criteria for
      organ procurement, we may be able to increase both the supply of transplantable
      organs and clarity in our understanding of death.

PMID- 9017414
TI  - Geographies of responsibility.

PMID- 9017415
TI  - Not just for breakfast anymore.

PMID- 9017416
TI  - Ethics Committees in Israel: for better or worse.

PMID- 9017417
TI  - Comparison of retroviral and adeno-associated viral vectors designed to express
      human clotting factor IX.
AB  - Several different designs for retroviral and adeno-associated virus (AAV) vectors
      were developed to express human clotting factor IX. Seven separate retroviral
      vectors were constructed, including chimeric long terminal repeat (LTR)-based
      designs, vectors containing splice donor/acceptor sites with internal ribosome
      entry sites (IRES), and vectors with an internal cytomegalovirus (CMV)- or
      hepatitis B virus (HBV)-derived promoter. Five AAV vectors were produced using
      the same cassette design where a viral promoter was used to transcribe a
      bicistronic mRNA containing factor IX and an IRES/neo gene. In the human
      hepatocyte cell line HepG2, the constructs were tested for factor IX production
      by ELISA, Northern blot, and Western blot, and for biological activity by
      normalization of the prolonged activated partial thromboplastin time (APTT) of
      factor IX-deficient plasma. All of the constructs produced biologically active
      factor IX in the range of 0.23-152 ng/24 hr per 10(6) cells (the HBV-promoted
      factor IX AAV vector was the least effective, and the CMV-promoted retroviral
      vector was the most active). Primary fibroblasts of both human and rabbit origin
      were also evaluated for factor IX production following transduction with viral
      vectors. Fibroblasts produced substantially more factor IX than the HepG2 cell
      line, with the best AAV vector synthesizing > 250 ng/24 hr per 10(6) cells and
      the best retroviral vector making > 900 ng/24 hr per 10(6) cells. Generally, we
      observed lower transduction efficiency and poorer expression with the AAV vectors
      versus retroviral vectors in these cell types.

PMID- 9017418
TI  - Systemic delivery of human growth hormone or human factor IX in dogs by
      reintroduced genetically modified autologous bone marrow stromal cells.
AB  - Canine bone marrow stromal cells were expanded to numbers in excess of 10(9)
      cells from the initial 10-20 ml of marrow aspirates and transfected to express
      high levels of human growth hormone (hGH) in vitro. Ex vivo-modified marrow
      stromal cells were used in a gene therapy model system for the systemic delivery
      of transgene products in dogs. Adherent bone marrow stromal cell cultures,
      established and expanded from iliac crest marrow aspirates from each of 8 dogs,
      were transfected with a hGH gene plasmid expression vector and shown to express
      from 0.54-3.84 micrograms/10(6) cells per 24 hr hGH in vitro. The transfected
      plasmid vector does not possess a eukaryotic origin of replication nor does it
      possess sequences required for efficient integration into the host cell genome.
      As such, expression was expected to be transient. Transfected cells were
      autologously reintroduced into each dog by either infusion into a foreleg vein or
      directly into iliac crest marrow. In two cases, the stromal cells were
      cryopreserved following transfection, and subsequently thawed and infused. In one
      case, the expanded stromal cells were first cryopreserved, and then thawed,
      recultured, transfected, and infused. Reintroduced cell numbers ranged from 2.2 x
      10(7) to 2.6 x 10(9), with total hGH expression capacities ranging from 62 to
      1,400 micrograms/24 hr. Plasma of each of the dogs contained detectable hGH for a
      mean of 3.1 days (SD +/- 0.8 day) ranging from 2 to 5 days following reinfusion
      of cells. Peak plasma levels ranged from 0.10 to 1.76 ng/ml. Similar hGH
      expression values, based upon total expression capacity of the cells infused and
      dog body weight, were obtained for all dogs. Vector-modified stromal cells were
      detectable, by polymerase chain reaction (PCR) analysis, in the peripheral
      circulation following reinfusion in all 4 dogs analyzed. In 3 of the dogs,
      modified stromal cells were detected for 8.5-15 weeks. In addition, modified
      stromal cells were detected in iliac crest marrow of 2 dogs for 9 and 13 weeks,
      respectively, following reinfusion. In another experiment, cultured bone marrow
      stromal cells were transfected with a human factor IX (hFIX) plasmid vector.
      Modified cells (5.57 x 10(8)), with a total hFIX expression capacity of 281
      micrograms/24 hr, were reinfused, resulting in detectable hFIX in plasma
      continuously for 9 days with a peak level of 8 ng/ml on day 1. These results
      demonstrate that the ex vivo bone marrow stromal cell system is a potentially
      powerful method by which to deliver secreted transgene product to the systemic
      circulation of large animals.

PMID- 9017419
TI  - A novel gene therapy strategy for elimination of prostate carcinoma cells from
      human bone marrow.
AB  - We report a novel means to purge bone marrow of a specific subset of prostate
      carcinoma cells based on transductional and genetic selectivity. Using both
      adenovirus-polylysine-DNA complexes and E1A/B-deleted replication-deficient
      adenoviruses, we have demonstrated a transductional preference of these vectors
      for the prostate carcinoma cell lines DU 145, LNCaP, and PC-3 over primary human
      bone marrow cells and the leukemia cell line KG-1. We have also shown a genetic
      selectivity of an anti-erbB-2 intracellular single-chain antibody (sFv) encoding
      adenovirus, Ad21, for the erbB-2-positive prostate carcinoma cell lines DU 145
      and LNCaP. Delivery of Ad21 resulted in cytotoxicity to the DU 145 and LNCaP, but
      not PC-3, cell lines and reduced the clonogenic capacity of DU 145 cells cultured
      alone or mixed with various ratios of irradiated human bone marrow. Finally,
      quantitative, competitive reverse transcription polymerase chain reaction (QC-RT
      PCR) analysis demonstrated that Ad21 could effectively reduce DU 145 and erbB-2
      positive primary prostate tumor contamination in bone marrow cultures. Delivery
      of Ad21 had no effect on the ability of progenitor cells to form colonies. These
      results suggest that an anti-erbB-2 sFv-encoding adenoviral vector is efficacious
      for removal of erbB-2-positive prostate carcinoma cells from human bone marrow,
      and demonstrates a novel method for ex vivo genetic purge of malignant cells from
      bone marrow for autologous bone marrow transplantation (ABMT) therapy.

PMID- 9017420
TI  - Exogenous surfactant enhances the delivery of recombinant adenoviral vectors to
      the lung.
AB  - Somatic gene therapy for pulmonary diseases must be accomplished in vivo,
      requiring the spread of a gene transfer vector across a vast expanse of
      respiratory epithelium. Surfactant, a naturally occurring protein and lipid
      mixture used to treat the respiratory distress syndrome of prematurity, disperses
      rapidly and evenly throughout the lung. We employed exogenous bovine surfactant
      (Survanta beractant) as a carrier vehicle for pulmonary delivery of a recombinant
      adenovirus expressing beta-galactosidase (beta-Gal). Rats treated with an
      adenovirus-beractant mixture demonstrated more uniform lobar distribution of
      transgene expression than rats treated with the same amount of virus in saline.
      Tissue homogenates were examined for quantitative beta-Gal expression by reaction
      with o-nitrophenol beta-n-galactopyranoside (ONPG). The degree of beta-Gal
      activity was affected by both the volume and type of carrier used to deliver the
      virus. At low volumes (0.5 ml, 1.3 ml/kg), beractant-treated animals demonstrated
      significantly greater pulmonary beta-Gal activity than saline-treated animals (p
      < 0.002) and untreated controls. At high volume (1.2 ml, 4 ml/kg), average beta
      Gal activity was similar between groups treated with beractant or saline, but was
      more variable within the saline treated group. Higher volumes of delivery medium
      were associated with increased levels of beta-Gal expression regardless of the
      carrier used. Survanta was well tolerated by the animals and did not affect the
      duration of transgene expression. Exogenous beractant provides a useful medium
      for delivering recombinant adenoviruses to the lung when diffuse distribution of
      transgene expression is desired.

PMID- 9017421
TI  - Parenteral gene therapy with p53 inhibits human breast tumors in vivo through a
      bystander mechanism without evidence of toxicity.
AB  - Mutations of the p53 tumor suppressor gene are the most frequently observed
      genetic lesion in human cancer. Previously, we found that multiple intravenous
      injections of a liposome:p53 complex inhibited the growth of a malignant human
      breast cancer cell line that was implanted into nude mice. In the present study,
      we evaluated the toxicity of the liposome:p53 complex and the mechanism of this
      in vivo treatment in reducing tumor growth. Intravenously delivered liposome:p53
      complex at dosages sufficient to inhibit human breast cancer in nude mice showed
      no evidence of toxicity. Clinical chemistries, complete blood counts, and
      histopathologic examination of various organs from the p53-treated groups did not
      demonstrate any difference from the control groups. To elucidate the mechanism by
      which the liposome:p53 complex inhibits cancer, the transfection efficiency of a
      liposome:chloramphenicol acetyltransferase (CAT) complex into the tumor was
      determined. Interestingly, less than 5% of the tumor was transfected with a
      liposome:CAT complex. A mechanism that could account for p53 reduction of tumor
      size and a low transfection efficiency is inhibition of angiogenesis. After one
      treatment, we found that the liposome:p53 complex reduced the number of blood
      vessels in the p53-treated group by approximately 60% compared to the control
      group (p < 0.001). The close correlation between the antitumor effect of p53 and
      the reduction of blood vessel density in the tumor suggests that p53 effects are
      mediated, at least in part, by an antiangiogenesis mechanism.

PMID- 9017422
TI  - Genetic immunotherapy of established tumors with adenovirus-murine granulocyte
      macrophage colony-stimulating factor.
AB  - Increased local production of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) by genetically modified tumor cells can induce specific antitumor
      cellular immunity. We constructed a recombinant adenovirus expressing murine GM
      CSF and tested it for therapeutic efficacy in a syngeneic murine lung cancer
      model system. In vitro transduction of Lewis lung carcinoma cells with adenovirus
      mGM-CSF suppressed tumor formation in syngenic mice (C57BL/6), and transduced and
      irradiated Lewis lung carcinoma cells induced regression of pre-established wild
      type tumors without in vitro selection for transductants. Low, but significant,
      levels of specific antitumor cytotoxic T lymphocytes (CTL) were observed in mice
      inoculated with GM-CSF but not with reporter virus-transduced tumor cells. GM-CSF
      transduced cells induced the accumulation of dendritic cells at the site of
      tumor, consistent with a mechanism involving improved tumor antigen presentation.
      These data suggest that transduction of tumor cells with recombinant GM-CSF
      adenovirus may be an effective and practical cancer gene therapeutic strategy.

PMID- 9017423
TI  - Modulation of erythropoietin delivery from engineered muscles in mice.
AB  - In most relevant diseases, the permanent systemic delivery of a therapeutic
      protein from engineered cells might be proposed only if secretion levels can be
      regulated. The tetracycline resistance operon of Escherichia coli provides a
      transcriptional regulatory system effective in mammalian cells, which could be
      used for that purpose. A chimeric transactivator (tTA) consisting of the
      tetracycline repressor fused to the transactivation domain of the herpes simplex
      virus VP16 protein stimulates transcription by binding a minimal cytomegalovirus
      (CMV) promoter containing repeats of the tetracycline operator (tetO-CMV).
      Binding is abolished by tetracycline, thus impairing promoter activation. We have
      transduced C2.7 myoblasts with two U3-deleted retroviral vectors containing these
      regulatory elements. The tetP-Epo vector expressed the murine erythropoietin
      (Epo) cDNA under the control of the tetO-CMV promoter. The D-De-tTA vector
      expressed tTA under the control of the muscle-specific human desmin enhancer
      promoter. Northern blot analysis showed background Epo mRNA expression in
      myoblasts. Myotubes differentiation induced tTA expression, leading to a 28-fold
      increase of Epo mRNAs, which was suppressed by tetracycline. Basal Epo secretion
      in myoblasts increased 23- to 41-fold during the formation of multinucleated
      myotubes, and turned back close to myoblast level when tetracycline was added.
      Myoblasts transduced with both vectors and treated with mitomycin with the aim to
      prevent tumor formation were engrafted in skeletal muscles of syngeneic C3H mice.
      Hematocrit levels were significantly higher in animals bearing cells transduced
      with both vectors than in control animals grafted with cells transduced with the
      Epo vector only. This difference was abolished when tetracycline was given to
      mice. These data indicate that the tetracycline regulatory elements can modulate
      transcription in the context of retroviral vector genomes, and that this system
      can be used to control the in vivo delivery of a therapeutic protein from
      genetically modified muscles.

PMID- 9017424
TI  - Efficient adenovirus-mediated ectopic gene expression of human lipoprotein lipase
      in human hepatic (HepG2) cells.
AB  - Gene therapy to deliver and express a corrective lipoprotein lipase (LPL) gene
      may improve the lipid profile and reduce the morbidity and potential atherogenic
      risk from hypertriglyceridemia and dyslipoproteinemia in patients with complete
      or partial LPL deficiency. We have used an E1-/E3- adenoviral vector, with an RSV
      driven human LPL cDNA expression cassette (Ad-RSV-LPL), to achieve high ectopic
      LPL gene expression in the human hepatoma cell line HepG2, an accepted
      hepatocellular model of lipoprotein metabolism. Ad-RSV-LPL transduction of HepG2
      cells with a multiplicity of infection (moi) between 12.5 and 100 yielded dose
      dependent increments in LPL mass and activity. Peak levels of LPL protein of
      2,032.1 +/- 274.5 ng/10(5) cells per ml (mol 100) correlated with increased
      activity of 92.7 +/- 22.6 mU/10(5) cells per ml relative to negligible LPL levels
      in Ad-RSV-LacZ (beta-galactosidase) controls. Exogenous LPL expression over a 5
      day period peaked at day 3. Susceptibility to inhibition by 1 M NaCl and an anti
      LPL monoclonal antibody confirmed that lipase activity was indeed derived from
      human LPL. Hydrolysis, by LPL-overexpressing HepG2 cells, of TG carried in very
      low-density lipoprotein (VLDL) showed that greater than 50% of the triglycerides
      (TG) disappeared after 4 hr of incubation. These results were compatible with
      FPLC evidence of a marked reduction in VLDL-TG. These results provide strong in
      vitro evidence that adenoviral-mediated ectopic expression of the human LPL gene
      could render hepatic cells capable of VLDL catabolism and thus support the
      possibility for in vivo adenoviral vector-mediated liver-targeted LPL gene
      therapy.

PMID- 9017425
TI  - Regional angiogenesis induced in nonischemic tissue by an adenoviral vector
      expressing vascular endothelial growth factor.
AB  - The feasibility of a single administration of a replication-deficient adenovirus
      (Ad) vector encoding the cDNA for human vascular endothelial growth factor (VEGF)
      (AdCMV.VEGF) to induce neovascularization in vivo in normal tissue was evaluated
      in retroperitoneal adipose tissue. Following administration of AdCMV.VEGF (10(9)
      pfu/50 microliters), maximal VEGF cDNA expression was observed at 2-5 days in the
      injected adipose tissue. No VEGF protein was detected at > or = 10 days in
      injected adipose tissue, and there was no increase in serum VEGF levels at any
      time. In vivo quantification of the number of blood vessels using 30x
      visualization of the adipose tissue demonstrated an increase in vessel number by
      10 days, plateauing by 30 days with a 123% increase in vessel number compared to
      the control vector AdCMV.Null, despite the fact that no VEGF protein was detected
      after 5 days. Consistent with the in vivo data, histologic quantification of
      capillary number demonstrated an increase by day 5, reaching a 38% increase over
      AdCMV.Null by day 30. These observations demonstrate that an Ad vector carrying
      the VEGF cDNA is capable of inducing the growth of new blood vessels in a
      regional fashion in a relatively avascular, normal organ. This suggests in vivo
      Ad-mediated gene transfer may be useful for therapeutic angiogenesis in the
      treatment of ischemic cardiovascular disease.

PMID- 9017426
TI  - A phase I study of recombinant adenovirus vector-mediated delivery of an anti
      erbB-2 single-chain (sFv) antibody gene for previously treated ovarian and
      extraovarian cancer patients.

PMID- 9017427
TI  - Multiple exposure to solvents in the workplace.

PMID- 9017428
TI  - Urinary malondialdehyde and 8-hydroxydeoxyguanosine as potential markers of
      oxidative stress in industrial art glass workers.
AB  - Previous epidemiological studies have indicated that industrial art glass workers
      have increased mortality risks for certain types of cancer and for cardio- and
      cerebrovascular disease. To test the hypothesis that increased oxidative stress
      might contribute to these increased mortality risks, the urinary levels of the
      lipid peroxidation product, malondialdehyde (MDA), and the oxidative DNA adduct,
      8-hydroxydeoxyguanosine (8OHdG) were determined in 343 workers (230 men and 113
      women) from the art glass industry in the southeast of Sweden. Of the study
      subjects, 199 (181 men and 18 women) were engaged in the process of glass
      production and were regarded as exposed, whereas the remainders performed
      clerical, warehouse and other service work and were regarded as unexposed. One
      hundred and sixteen were smokers (75 men and 41 women) and 215 were non-smokers
      (142 men and 73 women). The findings indicate that (a) exposure to industrial art
      glass work per se does not cause any major oxidative stress as measured by
      urinary levels of MDA and 8OHdG, (b) the effects from smoking per se are limited
      to increased lipid peroxidation among men, and (c) joint exposure to industrial
      art glass work and smoking may cause increased lipid peroxidation among men and
      increased DNA hydroxylation among both men and women. While these findings
      provide no evidence for increased oxidative stress due to industrial art glass
      work per se, the increased 8OHdG excretion, in workers who smoke may be
      associated with a higher risk of developing free radical-dependent degenerative
      diseases including cancer.

PMID- 9017429
TI  - Vegetative function diagnosis for early detection of lead intoxication.
AB  - In the search for the early effects of neurotoxic lead poisoning, vegetative
      function diagnosis is a potential approach, focusing on the behaviour of the
      cardiac rhythm. Four groups of male subjects (109 copper workers exhibiting mean
      lead levels in blood of 31.2 micrograms/dl after long-term lead exposure; 27
      control subjects having a similar job in the iron and steel industry without
      neurotoxic exposure; 35 reference subjects from Magdeburg University Hospital
      without neurotoxic exposure, and 5 subjects to whom benefits have been awarded
      for disability resulting from lead intoxication) were studied. All subjects
      underwent the same psychometric test battery. Special attention was paid to the
      restoration of vegetative tone after exposure. The more extensive the exposure to
      lead, the longer was the delay in restoration. This effect seems to be
      reversible, as workers heavily exposed to lead, but otherwise healthy, were more
      affected than the patients included in this investigation. Simply comparing the
      cardiac rhythm of exposed and non-exposed subjects at rest is not sufficient for
      early detection of lead intoxication. The behaviour of cardiac rhythm in humans
      at rest is the result of long-term influence by a wide range of factors, of which
      lead exposure is only one.

PMID- 9017430
TI  - Individual serum bile acids in apprentice spray painters in association with
      solvent exposure.
AB  - The effects of exposure to solvents on serum bile acids were investigated by
      comparing a group of apprentice vehicle spray painters (exposed group) with one
      of apprentice electricians. Apprentice spray painters from the study were
      subdivided into high- and low-solvent-exposure groups. Concentrations of
      individual serum bile acids (SBA) were measured and compared with conventional
      liver function tests (LFTs). Total, free, glycine- and taurine-conjugated SBA
      were consistently found to be present at higher levels in the spray painters than
      in the electricians, even at the beginning of the apprenticeship. Total SBA
      tended to increase in spray painters with increasing years of exposure during the
      apprenticeship, but this was significant at only one time point. No rises were
      observed over the sampling period in electricians. The mean values of individual
      and total SBA concentrations were all found to be higher in the high-exposure
      group than in the low-exposure group, with some differences reaching statistical
      significance. None of the routine liver biochemistry parameters was different
      between spray painters and electricians. gamma-Glutamyl transferase (GGT) was the
      only enzyme found to be significantly different between the high- and low
      exposure groups, but all values were within the normal range. This study suggests
      that occupational exposure even to low levels of solvent mixtures results in
      increases in SBA. The increased SBA may be indicative of a subclinical liver
      dysfunction. Alternatively, they may reflect solvent exposure only, with the
      raised levels having no pathologic implication or consequence.

PMID- 9017431
TI  - Carbon disulphide. IV. Cardiovascular function in workers in the viscose
      industry.
AB  - OBJECTIVE: The aim of the study was to examine whether an increase can be
      detected in the prevalence of coronary heart disease or a higher prevalence of
      unusual cardiological findings in workers with occupational exposure to carbon
      disulphide (CS2) at the level of the threshold limit value of 10 ppm currently
      valid in occupational medicine. METHODS: In a cross-sectional study we
      investigated 247 men occupationally exposed to CS2 and a comparable control group
      (n = 222). The current exposure to CS2 was measured using personal air monitoring
      and biological monitoring of all test persons. A cumulative exposure index
      (median of CS2 exposure in the past multiplied by the duration of employment) was
      calculated. In addition to collecting comprehensive anamnestic data on all
      persons, we carried out a physical examination, an ultrasound examination of the
      large arteries, a resting and exercise ECG and an echocardiographic examination.
      RESULTS: No increase could be found in the prevalence of coronary heart disease
      or of arteriosclerotic findings in the exposed subjects. There was no difference
      in the distribution of the performance of the two groups in the ergometric tests.
      The echocardiogram showed a median increase in the diameter of the left atrium
      and left ventricle of 1-2 mm in the exposed subjects. These differences could
      also be confirmed statistically after multiple linear regression analysis. The
      left ventricular, telesystolic diameter was positively associated (P < 0.05) with
      internal exposure (CS2 metabolite in urine), and fractional shortening revealed a
      plausible negative trend (P = 0.0755). Current external exposure (CS2 in air) and
      cumulative exposure did not influence any of the parameters investigated.
      CONCLUSION: The findings may indicate a negatively inotropic effect of CS2 so far
      unknown in man. However, no clinical relevance for this effect was apparent.

PMID- 9017432
TI  - Cyto- and genotoxic effects of coordination complexes of platinum, palladium and
      rhodium in vitro.
AB  - The growing industrial use of platinum group elements as catalysts, especially in
      automobile exhaust detoxification (trimetal catalytic converters), is causing
      increasing occupational and environmental pollution. The cytotoxic and mutagenic
      properties of industrially used coordination complexes of platinum, palladium and
      rhodium were investigated using the neutral red cytotoxicity assay on two
      established cell lines and the Salmonella typhimurium/microsome test system (Ames
      test). Cytotoxic effects of the platinum complexes, measured as ED50, occurred at
      test concentrations of 0.2 mM. The analogous palladium salts tested were 3 times
      less toxic with ED50 being 0.6 mM, while the rhodium salts proved to be 30 times
      less toxic (ED50 = 6 mM). Levels of toxicity of the different complexes of a
      particular metal did not differ significantly from each other, which indicates
      that the metal itself is responsible for the toxic effects. In the Ames test, the
      spontaneous mutation rates increased by factors of 3 to 20 when the four tester
      strains were exposed to the platinum complexes. The analogous rhodium compounds
      proved to be considerably less mutagenic, and palladium demonstrated no mutagenic
      potential. As all of the four tester strains contain different mutations, the
      mutagenic potential of platinum and rhodium complexes appears to be based on a
      variety of mechanisms that damage DNA. From these in vitro experiments, it can be
      concluded that water-soluble complex salts of rhodium are less toxic and have a
      smaller mutagenic potential than the analogous platinum complexes. For palladium
      there is no evidence of any mutagenic property. From this point of view, the
      development of a catalytic converter containing predominantly palladium may be a
      possible means of minimizing potential health risks from this exhaust
      detoxification technique.

PMID- 9017433
TI  - Occupational exposure to Cr(VI): comparison between chromium levels in
      lymphocytes, erythrocytes, and urine.
AB  - The relationships between chromium (Cr) levels in lymphocytes, erythrocytes,
      urine, and ambient air were compared among 14 chrome-platers from a metallurgic
      plant in Bulgaria and two groups of local controls, one from the same heavily
      polluted industrial town as the chrome-platers (n = 11) and one from a seaside
      resort town 100 km away (n = 6). Among the chrome-platers, the Cr concentration
      in peripheral lymphocytes was positively correlated with total Cr and Cr(VI)
      levels in ambient air and with Cr excretion in urine. As compared to the
      controls, the chrome-platers had mean Cr levels in lymphocytes twice as high, in
      erythrocytes ninefold higher, and in urine fourfold to eightfold higher. Although
      Cr levels in urine and lymphocytes were similar between the two control groups,
      levels in erythrocytes were 3 times higher among subjects from the industrial
      area than among those from the seaside town. The study suggests that lymphocyte
      Cr could be a good indicator of the Cr body burden caused by high exposures to
      Cr(VI), such as in electroplating operations. In these conditions, erythrocyte Cr
      may be less useful, possibly owing to increased toxicity due to the high affinity
      of erythrocytes for Cr. However, when exposure is lower, such as in most
      environmental situations, erythrocyte Cr should provide a better and more
      sensitive index than lymphocyte Cr. By contrast, urinary Cr, which provides
      information on total Cr exposure, including Cr(III) from dietary and
      environmental sources, does not seem to be of value for studying occupational
      exposure to Cr(VI).

PMID- 9017434
TI  - Temporary threshold shift of vibratory sensation induced by a vibrating handle
      and its gripping force.
AB  - OBJECTIVE: This study examines the effect of the force with which a vibrating
      handle is gripped on the temporary threshold shift of vibratory sensation (TTSv)
      induced by hand-arm vibration. METHODS: Six healthy subjects gripped a handle
      vibrating with a 1.3 octave-band vibration, with a central frequency of 200 Hz
      and an intensity of 39.2 m/s2. Exposure was for 1 min and 10 min, respectively.
      Gripping forces for the 1-min exposure were 5 N, 10 N, 40 N and 80 N,
      respectively, with 0 N push-pull force. Gripping forces for the 10-min exposure
      were the same as for the 1-min exposure but omitting 80 N. The vibratory
      sensation threshold at 125 Hz was measured before and after exposure of an
      exposed fingertip to vibration. The differences measured determine TTSv.t at time
      t. TTSv.t determines TTSv.0, that is, the temporary threshold shift of vibratory
      sensation immediately after exposure to vibration according to the estimate made
      on the basis of the preceding study. The same experimental conditions were
      repeated 3 times on different days in a soundproof and thermoregulated room.
      RESULTS: Our findings show that TTSv increases significantly with increasing
      gripping force. We also determined the quantitative relationships between TTSv.0
      and gripping force as described by the equation TTSv.0 = exp(kf x F + Cf). where
      kt and Cf are constants and F is gripping force. CONCLUSION: This study revealed
      the importance of ergonomic design in reducing the force with which a vibrating
      handle is gripped to prevent an adverse effect of local vibration. The equation
      devised may help in the quantitative assessment of the effect of reduced gripping
      force.

PMID- 9017435
TI  - Acute effects of 1,1,1-trichloroethane inhalation on the human central nervous
      system.
AB  - The object of this study was to examine the immediate nervous effects of variable
      1,1,1-trichloroethane (TCE) exposure combined with physical exercise. The effects
      on the quantitative electroencephalography (EEG), visual evoked potentials (VEP)
      and body sway were analyzed. Nine male volunteers were exposed to either a stable
      or a fluctuating exposure pattern with the same time-weighted average
      concentration of 200 ppm (8.1 mumol/l). In both cases, the subjects engaged in
      physical exercise during the exposures. Exercise alone induced an increase in the
      dominant alpha frequency in the EEG and, after an initial drop, an increase in
      the alpha percentage with a concomitant decrease in theta, whereas delta and beta
      bands remained unaffected. By contrast, exposure to TCI and exercise did not
      affect the alpha, theta or delta activities but induced changes in beta during
      the morning recordings at peak exposure to TCE. The body sway tended to decrease
      slightly during the fluctuating TCE exposure, and the later peaks in VEPs showed
      slight prolongations. Overall, no deleterious effects of exposure were noted.

PMID- 9017436
TI  - Biological monitoring of deltamethrin exposure in greenhouses.
AB  - This study examined the possibility of using biological monitoring to assess
      deltamethrin exposure among greenhouse workers. The synthetic pyrethroid
      deltamethrin was sprayed in five greenhouses by cold for generators, and the
      exposure was biologically monitored by analysing the concentration of its
      metabolite, 3-phenoxybenzoic acid, by a gas chromato-graphic method after
      derivatization with pentafluorobenzyl bromide. 3-Phenoxybenzoic acid was found in
      the urine of two of the ten workers studied. The urine concentration of the
      metabolite varied from 2.4 to 51.7 micrograms/l. These results show that 3
      phenoxybenzoic acid is suitable for biological monitoring for the assessment of
      exposure to deltamethrin.

PMID- 9017437
TI  - Urinary hexane diamine as an indicator of occupational exposure to hexamethylene
      diisocyanate.
AB  - The occupational exposure of 19 men to hexamethylene diisocyanate (HDI) vapour
      was monitored during one 8-h shift. It ranged from 0.30 to 97.7 micrograms/m3.
      This was compared with the urinary output of hexane diamine (HDA) liberated by
      acid hydrolysis from its conjugates in post-shift samples. The excretion varied
      from 1.36 to 27.7 micrograms g creatinine, and there was a linear association of
      HDI air concentration with urinary HDA excretion. The validity of the urinary
      analysis was confirmed by simultaneous blind analysis in another laboratory. The
      results had an excellent linear concordance. Thus, it seems that while the gas
      chromatographic-mass spectrometric detection method requires sophisticated
      apparatus, the results are very useful to occupational health practices. A
      biological exposure index limit of 19 micrograms HDA/g creatinine in a post-shift
      urine specimen is proposed as an occupational limit level of HDI monomer (time
      weighted average = 75 micrograms/m3). Most importantly, biological monitoring of
      HDA is sensitive enough to be used at and below the current allowable exposure
      limit levels.

PMID- 9017438
TI  - Increase in CD57 + CD16-lymphocytes in workers exposed to benzidine and beta
      naphthylamine: assessment of natural killer cell subpopulations.
AB  - Previously, we found a decrease in CD4 + CD45RA + T lymphocytes in workers
      exposed to the aromatic amines (AAs) [benzidine (BZ) and beta naphthylamine
      (BNA)]. For further investigation of the effects of AAs on lymphocyte
      subpopulations, we measured natural killer (NK) cell subpopulations using two
      color staining with anti-Leu7 (CD57) and anti-Leu11 (CD16) monoclonal antibodies
      in peripheral blood in 78 male dyestuff workers. The workers had been exposed to
      AAs before 1972 at a chemical plant, either in the production of AAs (40 workers,
      high-exposure group) or in other work that involved handling dyestuffs (38
      workers, low-exposure group). The controls were 30 "healthy" male volunteers
      without a history of occupational exposure to AAs or hazardous chemicals. The
      number of CD57 + CD16- cells in the high-exposure group was significantly higher
      than that in the controls (P < 0.01, analysis of covariance with age as a
      covariate). No significant differences were found in CD57 + CD16-, CD57 + CD16+
      and CD57- CD16 + NK cells between the low-exposure group and the controls. It is
      suggested that a decrease in the number of CD4+ T lymphocytes following exposure
      to AAs might be compensated by the increase in CD57 + CD16- cells, i.e.
      circulating peripheral lymphocytes with poor NK cell activity.

PMID- 9017439
TI  - Serum erythropoietin and blood lead concentrations.
AB  - The aim of the study was to test the hypothesis that high blood lead levels are
      associated with depressed serum erythropoietin concentrations in workers
      occupationally exposed to lead. The results in exposed workers and in a control
      group of unexposed subjects were compared. Blood lead values were < or = 20
      micrograms/dl in unexposed subjects and > or = 30 micrograms/dl in exposed
      subjects. The two groups of exposed workers and the control population were
      matched for sex and age. Hemoglobin levels were not affected by blood lead values
      and did not differ significantly between the three groups. The two-tailed,
      nonparametric Mann-Whitney U-test was used to compare unpaired groups. The
      Spearman rank correlation test was used to evaluate the dose-effect relationship
      between Pb and EPO. The analysis of the data indicate that erythropoietin values
      are significantly lower in exposed subjects than a controls. However no
      correlation was demonstrated between blood lead concentrations and erythropoietin
      in any group.

PMID- 9017440
TI  - delta IK17: an antigen expressed on human lymphocytes.
AB  - Anti delta IK17 monoclonal antibody was produced by fusing SP2/0/Ag 14 myeloma
      with spleen cells of BALB/c mice immunized with normal human thymocytes. a delta
      IK17 antibody recognizes a 44kD cell surface protein detected on human
      lymphocytes. delta IK17 is expressed on human thymocytes, CD4+ and CD8+ T cell
      subsets, B, NK cells, as well as on activated cells. The antigen is detected on
      cells during the early, intermediate and late stages of lymphocyte maturation. In
      addition, the expression of the antigen is correlated with ontogenesis. A T+
      delta IK17+ subpopulation responded poorly to TPA stimulation and provided a
      better helper signal for PWM-induced IgM synthesis than T+ delta IK17- cells. In
      addition, different levels of delta IK17 expression were detected in several
      hematological diseases tested.

PMID- 9017441
TI  - delta IK17 antigen: a possible early marker of cancer development.
AB  - delta IK17 is a 44 kD molecule located on the surface of T, B and NK cells in
      normal peripheral blood mononuclear cells (PBMC) (1). The portion of PBMC
      expressing delta IK17 was determined in 52 patients with benign breast diseases,
      182 patients with breast malignancies and 132 healthy individuals. The percentage
      of delta IK17-positive cells was significantly lower in the early stages (I-IIA)
      of malignancy compared to that of healthy donors. However, the percentage of PBMC
      expressing delta IK17 tended to increase as the stage of the disease advanced.
      delta IK17 seems to be the only antigen among the other cellular markers tested
      (CD2, CD4, CD8, HLA-DR) with a statistically significant correlation between a
      low percentage of positive cells and the early stages of malignancy and between a
      high expression and advanced disease. Its potential use as a tumor marker in
      breast cancer is discussed here.

PMID- 9017442
TI  - CA549 and TPS patterns in the diagnosis and staging of patients with breast
      carcinoma.
AB  - This study compares the clinical value of the breast cancer tumour makers CA549
      and TPS, and their tandem use when one or both markers indicate abnormality. For
      144 patients presenting with active disease, 33 were classified as Stage I, 37 as
      Stage II, 40 as Stage III and 34 as Stage IV. For these patients the sensitivity
      of CA549 using a cut-off of 10 U/ml was 27%, 32%, 42% and 79%, respectively. The
      sensitivity of TPS for each stage using a cut-off of 100 U/l was 12%, 22%, 28%
      and 73%, respectively. At these cut-off levels, 36%, 46%, 63% and 91% of
      patients, respectively, have either CA549 or TPS or both markers raised. For 161
      patients with diagnosed benign breast disease, the specificity of marker levels
      was 96% for CA549, 88% for TPS and 84% for tandem use. CA549 is shown to be
      superior to TPS and this was confirmed by Receiver Operating Characteristic (ROC)
      analysis using variable threshold levels, with the areas under the curves for all
      stages combined being 0.74 +/- 0.03 (ISD) and 0.66 +/- 0.03, respectively. The
      corresponding area under the curve for tandem use (0.75 +/- 0.03) is marginally
      greater than for either individual marker, although the difference with respect
      to CA549 is statistically insignificant.

PMID- 9017443
TI  - False positive tumor markers: elevation in patients with breast cancer on FAC
      type chemotherapy and correlation with the development of hand-foot syndrome.
AB  - Breast cancer patients on dose-intensive chemotherapy often have elevated tumor
      markers during the course of treatment. Our objective was to estimate the
      incidence of a "false positive" tumor marker screen and to determine whether hand
      foot epithelial damage was correlated. Data from 53 patients with high risk
      primary breast cancer who had undergone adjuvant or neoadjuvant 5FU-containing
      chemotherapy (FAC or FAC plus G-CSF) for 3 to 12 months were reviewed. The
      relationship between tumor marker elevation and disease recurrence, regimen
      intensity, and the occurrence of hand-foot syndrome was examined. Thirty-three of
      the 53 patients had elevated tumor markers in the absence of recurrent disease.
      The false positive rate was higher in patients who underwent FAC plus G-CSF
      chemotherapy than in patients who underwent FAC chemotherapy (92% vs 55%, p =
      .01). A false positive marker screen was associated with the occurrence of hand
      foot syndrome even when the effect of regimen was accounted for by stratification
      (p = .01). Tumor marker screening of breast cancer patients on this type of
      adjuvant chemotherapy has poor specificity for recurrent malignancy. These data
      suggest tumor marker elevation may be an indicator of epithelial toxicity during
      chemotherapy, manifested clinically as hand-foot syndrome.

PMID- 9017444
TI  - Are diabetic metabolic compensation and CA19.9 really correlated?
AB  - Diabetes has been claimed to be a risk factor for pancreatic carcinoma, but it is
      probably a consequence of gland invasion from the neoplastic tissue. A link
      between diabetes and pancreatic carcinoma was suggested by means of biochemical
      markers of the diseases, namely glycated hemoglobin and CA19.9. Moreover, CA19.9
      was proposed as a sensitive and useful marker of the severity of exocrine damage
      in diabetes, since the mucin decreased when metabolic compensation improved. We
      examined 64 diabetic patients (36 insulin dependent, 16 non insulin dependent, 12
      treated with diet) by measuring CA19.9 using two different immunometric methods
      and glycemia and glycated hemoglobin. We observed that a correlation between
      CA19.9 and biochemical markers of metabolic compensation of diabetes was
      inexistent and no differences between insulin dependent and non insulin dependent
      patients were found. A high concentration of CA19.9 in a diabetic patient should
      be interpreted and evaluated in the same manner as for a non diabetic patient.

PMID- 9017445
TI  - Generation of human monoclonal anti-idiotypic antibodies with specificity to the
      murine monoclonal anti-CA 125 antibody B43.13.
AB  - Two human monoclonal antibodies, HID-7E7 and ROB-6F2, were produced by EBV
      transformation of peripheral blood lymphocytes (PBL). PBL were obtained from a
      patient with ovarian cancer who had been exposed several times to a Tc-99m
      labeled murine monoclonal anti-CA 125 antibody (B43.13, Biomira, Edmonton) for
      immunoscintigraphy. The HID-7E7 and ROB-6F2 producing B-cells were cloned with a
      limiting dilution technique and have shown stable immunoglobulin secretion within
      a period of three years. The human monoclonal antibodies HID-7E7 and ROB-6F2 are
      of the IgG isotype, and bind with significant affinity to the murine monoclonal
      antibody B43.13, which was used for immunoscintigraphy. Binding affinity of ROB
      6F2 to other murine antibodies could not be detected. Cross reactivity of HID-7E7
      to a murine anti-CEA monoclonal antibody was observed. In order to verify the
      anti-idiotypic character of the generated human antibodies, the ability of HID
      7E7 and ROB-6F2, respectively, to inhibit the formation of the CA125/B43.13
      complex is demonstrated via an enzyme-linked immunosorbent assay. These human
      anti-idiotypic antibodies are possible candidates for immunotherapy of ovarian
      cancer in patients with a small tumor burden following surgery and/or
      chemotherapy.

PMID- 9017446
TI  - Hepatoid gastric carcinoma. A case report.
AB  - Alpha-fetoprotein (AFP) is normally produced by primary hepatic neoplasms and
      germ cell tumors. There have, however, been reports of its production in cases of
      gastrointestinal tract adenocarcinoma. Gastric hepatoid carcinomas constitute a
      clinicopathological entity of recent acquisition and have certain common
      characteristics, which include the presence of hepatoid foci and frequent liver
      metastases, even in cases of early gastric cancer, and increasing serum AFP
      levels. In this study the case of one patient who underwent gastric resection and
      presented clinical, humoral, histological and immunohistochemical characteristics
      typical of hepatoid gastric carcinoma is reported. More biological studies, as
      well as precise criteria for pathological definition and therapy, are still
      necessary for a better understanding of this pathology.

PMID- 9017447
TI  - Cell surface CD44v5 levels correlate with progesterone receptors and a tumor size
      > 2 cm in infiltrating ductal carcinomas of the breast.

PMID- 9017454
TI  - Analysis of disease-causing genes and DNA-based drugs by capillary
      electrophoresis. Towards DNA diagnosis and gene therapy for human diseases.
AB  - Rapid progress in the Human Genome Project has stimulated investigations for gene
      therapy and DNA diagnosis of human diseases through mutation or polymorphism
      analysis of disease-causing genes and has resulted in a new class of drugs, i.e.,
      DNA-based drugs, including human gene, disease-causing gene, antisense DNA, DNA
      vaccine, triplex-forming oligonucleotide, protein-binding oligonucleotides, and
      ribozyme. The recent development of capillary electrophoresis technologies has
      facilitated the application of capillary electrophoresis to the analysis of DNA
      based drugs and the detection of mutations and polymorphism on human genes
      towards DNA diagnosis and gene therapy for human diseases. In this article the
      present state of studies on the analysis of DNA-based drugs and disease-causing
      genes by capillary electrophoresis is reviewed. The paper gives an overview of
      recent progress in the Human Genome Project and the fundamental aspects of
      polymerase chain reaction-based technologies for the detection of mutations and
      polymorphism on human genes and capillary electrophoresis techniques. Attention
      is mainly pad to the application of capillary electrophoresis to polymerase chain
      reaction analysis, restriction fragment length polymorphism, single strand
      conformational polymorphism, variable number of tandem repeat, microsatellite
      analysis, hybridization technique, and monitoring of DNA-based drugs. Possible
      future trends are also discussed.

PMID- 9017455
TI  - Cyclodextrins and enantiomeric separations of drugs by liquid chromatography and
      capillary electrophoresis: basic principles and new developments.
AB  - Investigation of individual drug enantiomers is required in pharmacokinetic and
      pharmacodynamic studies of drugs with a chiral centre. Cyclodextrins (CDs) are
      extensively used in high-performance liquid chromatography as stationary phases
      bonded to a solid support or as mobile phase additives in HPLC and capillary
      electrophoresis (CE) for the separation of chiral compounds. We describe here the
      basis for the liquid chromatographic and capillary electrophoretic resolution of
      drug enantiomers and the factors affecting their enantiomeric separation. This
      review covers the use of CDs and some of their derivatives in studies of
      compounds of pharmacological interest.

PMID- 9017456
TI  - Endogenous alkaloids in man. XXVI. Determination of the dopaminergic neurotoxin 1
      trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) in biological samples
      using gas chromatography with selected ion monitoring.
AB  - Highly chlorinated beta-carbolines have a potential in vivo relevance to
      Parkinson's disease. In this paper, a gas chromatographic method for the
      determination of the neurotoxic 1-trichloromethyl-1,2,3,4-tetrahydro-beta
      carboline (TaClo), the condensation product of tryptamine and chloral hydrate, is
      described. The specific and sensitive assay involves purification of the
      biological samples by solid-phase extraction with C18 cartridges, derivatization
      with heptafluorobutyric anhydride, and chromatography on a non-polar fused-silica
      capillary column. Detection of TaClo was achieved by the registration of
      characteristic mass fragments of the TaClo heptafluorobutyric amide derivative
      using selected ion monitoring. The method was utilized to detect and quantify
      TaClo in blood, urine, bile, faeces, and brain tissue of rats treated with this
      alkaloid-type heterocycle. Four-fold deuterium-labelled TaClo was used as an
      internal standard.

PMID- 9017457
TI  - Heterogeneity of hemoglobin A1d: assessment and partial characterization of two
      new minor hemoglobins, A1d3a and A1d3b, increased in uremic and diabetic
      patients, respectively.
AB  - We have separated and quantified two new minor hemoglobins named HbA1d3a and
      HbA1d3b. The level of HbA1d3a was significantly higher in uremic than in non
      uremic patients (3.00 +/- 0.50% vs. 1.28 +/- 0.26% of total hemoglobin). It
      correlated well with carbamylated hemoglobin (r = 0.80, n = 81, p < 0.002) and
      with plasma urea concentration (r = 0.78, n = 81, p < 0.002). These data and the
      electrospray ionization mass spectrometric analysis provide strong evidence that
      HbA1d3a is an alpha-chain modified by carbamylation. The HbA1d3b level an
      diabetic patients was found to be 1.6-fold that in non-diabetic subjects (3.00 +/
      0.49 vs. 1.90 +/- 0.33). This was attributed to HbA1d3 modified by glycation.
      Indeed HbA1d3b correlated significantly with HbA1c (r = 0.71, p < 0.002) and with
      serum glucose level (r = 0.62, p < 0.002). These two new minor hemoglobins may
      serve as complements for the objective assessment of averaged long-term uremia
      and glycemia in uremic and diabetic patients.

PMID- 9017458
TI  - Enhanced thin-layer chromatographic separation of GM1b-type gangliosides by
      automated multiple development.
AB  - Enhancement in separation of gangliosides on silica gel precoated high
      performance TLC plates has been obtained by automated multiple development
      chromatography. A less polar mixture of the standard solvent chloroform-methanol
      20 mM aqueous CaCl2 (120:85:20, v/v) was used. Lowering the water content
      achieved separation of two complex monosialoganglioside fractions, isolated from
      murine YAC 1 T lymphoma and MDAY-D2 lymphoreticular cells. Three-fold
      chromatography in the solvent chloroform-methanol-20 mM aqueous CaCl2 (120:85:14,
      v/v) resulted in TLC separation of GM1b-type gangliosides, substituted with C24
      and C16 fatty acids and with Neu5Ac and Neu5Gc as well, which could not be
      achieved by unidirectional standard chromatography. Compared to conventional
      single chromatography, the technique described allows high-resolution separation
      of extremely heterogenous ganglioside mixtures and offers a convenient tool for
      both analytical and preparative TLC.

PMID- 9017459
TI  - Analysis of single erythrocytes by injection-based capillary isoelectric focusing
      with laser-induced native fluorescence detection.
AB  - A modified version of capillary isoelectric focusing (cIEF) was developed to
      separate hemoglobin variants contained within single human erythrocytes. Laser
      induced native fluorescence with 275 nm excitation was used to detect the
      separated hemoglobins. In this method, baseline fluctuations were minimized and
      detection sensitivity was improved by using dilute solutions of anolyte,
      catholyte, and carrier ampholytes (with methylcellulose). Since electroosmotic
      flow was used for mobilization of the focused bands, separation and detection
      were integrated into a single step. The capillary was first filled with only
      ampholyte solution, and the cell (or standard) was injected as in capillary zone
      electrophoresis. The approximately 90 fl injection volume for individual cells is
      7 x 10(4) times lower than those previously reported. Adult (normal and elevated
      A1), sickle (heterozygous), and fetal erythrocytes were analyzed with the amounts
      of hemoglobins AO, A1c, S and F determined. The pH gradient for cIEF was linear
      (r = 0.9984), which allowed tentative identification of Hb Fac. Variants
      differing by as little as 0.025 pl units were resolved.

PMID- 9017461
TI  - Sensitive gas chromatographic method for determination of mercapturic acids in
      human urine.
AB  - A method was developed for sensitive determination of the specific benzene
      metabolite S-phenylmercapturic acid and the corresponding toluene metabolite S
      benzylmercapturic acid in human urine for non-occupational and occupational
      exposure. The sample preparation procedure consists of liquid extraction of urine
      samples followed by precolumn derivatization and a clean-up by normal-phase HPLC.
      Determination of analytes occurs by gas chromatography with electron-capture
      detection. With this highly sensitive method (detection limits 60 and 65 ng/l,
      respectively) urinary S-phenylmercapturic and S-benzylmercapturic acid
      concentrations for non-occupationally exposed persons (e.g. non-smokers) can be
      measured precisely in one chromatographic run. Validation of the method occurred
      by comparison with a HPLC method we have published recently.

PMID- 9017460
TI  - Elaidic and trans-vaccenic acids in plasma phospholipids as indicators of dietary
      intake of 18:1 trans-fatty acids.
AB  - Octadecenoic (18:1) trans-fatty acid fractions from margarine, butter and plasma
      phospholipids (PL) were isolated by silver ion TLC, and nine positional isomers
      (n-11-n-3) were identified by GC-MS based on their ozonolysis products. The GC
      analysis of the isolated fractions gave similar peak profiles and separated seven
      trans-isomers (n-11-n-6 and n-3). Without a preceding isolation step, the
      reproducibility of the GC method for plasma PL elaidic (18:1 n 9 trans) and trans
      vaccenic acids (n-7) was 3.4 and 2.7% (R.S.D.), respectively. These trans-isomers
      were rapidly incorporated and cleared in plasma PL and they closely reflected
      both increased and decreased intake of 18:1 trans-fatty acids during moderate fat
      substitutions. Significant associations between high-density lipoprotein
      cholesterol (HDL-C) and PL elaidic and trans-vaccenic acids appeared in habitual
      margarine users only.

PMID- 9017462
TI  - Determination of urinary mercapturic acids of styrene in man by high-performance
      liquid chromatography with fluorescence detection.
AB  - A method for the determination of urinary N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L
      cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2) in man was
      developed. Clean-up of urine samples was obtained by a chromatographic technique,
      using a short reversed-phase precolumn; purified samples were then deacetylated
      with porcine acylase I for 16 h at 37 degrees C and deproteinized by centrifugal
      ultrafiltration. Derivatization was performed with o-phthaldialdehyde and 2
      mercaptoethanol and the fluorescent derivatives were separated on a reversed
      phase analytical column with a gradient mobile phase consisting of 50 mM acetate
      buffer (pH 6.5) and methanol. The retention times of the diastereoisomers of M1
      (M1-"S" and M1-"R") were 52.8 and 73.7 min, respectively: M2 diastereoisomers
      eluted as a single peak at 70.5 min. The fluorescence detector was set at 330 nm
      (excitation) and 440 nm (emission). The detection limit (at a signal-to-noise
      ratio of three) was about 7 micrograms/1. The method was applied to 25 urine
      samples from workers exposed to styrene. A relationship was found between urinary
      mandelic and phenylglyoxylic acids and mercapturic acids specific for styrene.
      Urine samples from ten non-exposed subjects showed no detectable amounts of
      analytes.

PMID- 9017463
TI  - Selective determination of haloperidol in human serum: surface ionization mass
      spectrometry and gas chromatography with surface ionization detection.
AB  - Surface ionization organic mass spectrometry (SIOMS) has been performed on the
      clinically important drug haloperidol using quadrupole mass spectrometry in which
      the thermal ion source has a rhenium oxide emitter. The surface ionization (SI)
      mass spectrum is presented, interpreted in a purely empirical way by means of
      evidence from previous investigations, and then compared to results from
      conventional electron impact (EI) ionization. An approach to detection of this
      drug in serum by gas chromatography (GC) with a surface ionization detector (SID)
      and GC-SIOMS is described. This approach demonstrates that (a) haloperidol is
      efficiently surface-ionized, giving a unique SI mass spectrum, (b) experimental
      results rationalize the combined sensitivity and selectivity of the GC-SID for
      the examined drug, (c) the detection limit for haloperidol in serum is 1.1 ng/ml
      (S/N = 3) by GC-SID (the coefficients of variation of the assay are generally
      low, i.e., below 8.5%) and (d) the GC-SIOMS coupling can be used for sensitive
      and selective detection of haloperidol in serum.

PMID- 9017464
TI  - Determination of lincomycin residues in salmon tissues by gas chromatography with
      nitrogen-phosphorus detection.
AB  - A sensitive method for the determination of lincomycin residues in fish tissues
      is described. Lincomycin was extracted from fish tissues with phosphate buffer
      (pH 4.5). The extract was concentrated with a C18 solid-phase extraction
      cartridge and further cleaned up by solvent extraction. Lincomycin was
      derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide to form a
      trimethylsilyl derivative before being analyzed by gas chromatography with
      nitrogen-phosphorus detection. Coumaphos was used as the internal standard.
      Assays showed good linearity in the range 25-250 ppb (ng/g) (r = 0.9994).
      Recoveries of fortified lincomycin at 50, 100 and 200 ppb were > 80% with
      relative standard deviations < 6%. The limit of detection of the method was 1.7
      ppb and the limit of quantitation was 3.8 ppb.

PMID- 9017465
TI  - Liquid chromatographic determination of manidipine in serum with electrochemical
      detection.
AB  - A highly sensitive and selective method for determining a dihydropyridine calcium
      antagonist, manidipine, by liquid chromatography using column switching with
      electrochemical detection was developed. Manidipine in serum was extracted by a
      rapid and simple procedure based on C8 bonded-phase extraction and then silica
      extraction. Manidipine and nilvadipine as an internal standard were separated on
      a C8 bonded-phase HPLC column and detected by high conversion efficiency
      amperometric detection at +0.7 V. Manidipine and nilvadipine (I.S.) were
      separated from an endogenous interference peak in serum and concentrated on a pre
      column (C18) by column switching using an isocratic mobile phase, and then the
      corresponding fractions were introduced to an analytical column with a C8
      stationary phase. Determination of manidipine was possible over the concentration
      range 0.5-10 ng/ml: the limit of detection was 0.3 ng/ml. The recovery of
      manidipine added to serum was 93.1-98.4% with coefficients of variation of less
      than 7.1%. The method is applicable to drug level monitoring in the serum of
      healthy volunteers treated with manidipine and to the analysis of
      pharmacokinetics.

PMID- 9017466
TI  - Sensitive analytical method for the novel H1-receptor antagonist HSR-609 in human
      plasma and urine by high-performance liquid chromatography with pre-column
      fluorescent derivatization.
AB  - A simple and sensitive method for quantitation of HSR-609 (I) in human plasma and
      urine was developed using HPLC with the fluorescence labelling reagent 4-(N,N
      dimethylaminosulfonyl)-7-N-piperazino-2,1,3-benzox adi azole (DBD-PZ). Compound I
      was extracted from human plasma and urine, and derivatized by reaction with DBD
      PZ in the presence of Mukaiyama reagent A, an equimolar solution of 2,2'
      dipyridyl disulfide (DPDS) and triphenylphosphine (TPP) in acetonitrile. The
      reaction mixture was cleaned up by liquid liquid extraction following the
      derivatization. The conjugate was analyzed by ion-pair-HPLC with fluorometric
      detection. The quantitation limits for I were 0.5 ng/ml in plasma and 5 ng/ml in
      urine. Using this method, plasma concentration and urinary excretion of I were
      studied after oral administration of I to human volunteers.

PMID- 9017467
TI  - Trace analysis of albendazole and its sulphoxide and sulphone metabolites in milk
      by liquid chromatography.
AB  - Analytical methodology for determination of albendazole and its sulphoxide and
      sulphone metabolites in milk at levels down to 2-5 ng/ml has been developed.
      Extraction was carried out with ethyl acetate under alkaline conditions, and
      extracts were analyzed on a silica-based C18 column in the presence of positively
      charged pairing ions. Accuracy data showed overall recoveries ranged from 78.4%
      to 100%, whereas precision data, based on within and between-day variation,
      suggested overall precision values better than 4.9%. The method was successfully
      applied to determine residues in milk of a dairy cow orally given albendazole.

PMID- 9017468
TI  - Determination of bezafibrate, ciprofibrate and fenofibric acid in human plasma by
      high-performance liquid chromatography.
AB  - A selective high-performance liquid chromatographic method to assess either
      bezafibrate, ciprofibrate or fenofibric acid plasma levels is described. Drugs
      are extracted with diethyl ether, after acidification with HCL. An isocratic
      acetonitrile 0.02 M H3PO4 (55:45) mobile phase, a C18 microns) column and UV
      detection are used. The LOQ found was 0.25 microgram/ml for the three fibrates.
      Intra- and inter-assay accuracy ranges were 90-107% and 82-111%: 96-115% and 94
      107%: 94-114% and 94-126% for bezafibrate, ciprofibrate and fenofibric acid,
      respectively. Intra- and inter-assay precision (C.V.% ranges) were 1.72-3.06% and
      2.66-7.67%: 1.88-4.64% and 0.62-2.99%: 1.26-4.69% and 3.56-7.17% for the three
      fibrates studied. Its sensitivity, accuracy and precision make it a useful tool
      for monitoring plasma levels of these drugs in a clinical setting and for
      research purposes.

PMID- 9017469
TI  - Evidence of metal binding activities of pentadecapeptide from Panax ginseng.
AB  - A tetradecapeptide from ginseng (Panax ginseng) root showing anti-lipolytic
      activity in an isolated rat fat cell assay was chemically synthesized for
      analysis of metal binding activities in vitro. Binding activities against several
      metal ions were analysed by measuring mobility shifts during capillary zone
      electrophoresis experiments. The ginseng polypeptide (GPP) showed the greatest
      increase in effective molecular electrophoretic mobility in the presence of Mg2+.
      Mobility was also affected in the presence of La3+, Mn2+, Ca2+ and Zn2+ ions.
      Analysis with the dye Stains-all revealed GPP to possess a cation binding site
      similar to those in Ca(2+)-binding proteins. GPP thus appears to be a metal
      binding peptide. The results of this analysis suggested that GPP may perform its
      anti-lipolytic activities through an ability to modulate the level of free
      cellular Mg2+ and Mn2+ ions.

PMID- 9017470
TI  - Micropreparation of hemopoietic stem cells from the mouse bone marrow suspension
      by gravitational field-flow fractionation.
AB  - Gravitational field-flow fractionation is a relatively simple experimental
      technique. This method was used for the characterization of stem cells from mouse
      bone marrow. Because these cells are bigger than the other cells in bone marrow,
      it is possible to separate them from the mixture. The fractions collected after
      passing through the separation channel were characterized using a Coulter Counter
      and used for transplantation into irradiated mice.

PMID- 9017471
TI  - Rapid method for the analysis of itraconazole and hydroxyitraconazole in serum by
      high-performance liquid chromatography.
AB  - An assay for the determination of itraconazole and its active metabolite
      hydroxyitraconazole in serum has been developed, using ketoconazole as internal
      standard. The procedure involved a one-step liquid-liquid extraction of the drug,
      its metabolite and the internal standard, followed by their separation by
      reversed-phase HPLC. In this paper the validation of this method is described.

PMID- 9017472
TI  - High-performance chromatographic assay for the sulphoxide metabolite of 2'-deoxy
      3'-thiacytidine in human urine.
AB  - A high-performance liquid chromatographic method is described for the
      determination in human urine of GI138870X, the sulphoxide metabolite of a novel
      dideoxynucleoside analogue, 2'-deoxy-3'-thiacytidine (lamivudine). GI138870X was
      extracted from human urine using Empore SDB RPS solid-phase extraction disks
      prior to reversed-phase chromatography with UV detection. The method has shown to
      be valid over the concentration range 0.5-100 micrograms/ml using a 0.5-ml sample
      volume.

PMID- 9017473
TI  - Validated assay for the determination of celiprolol in plasma using high
      performance liquid chromatography and a silanol deactivated reversed-phase
      support.
AB  - Previously reported methods for the determination of celiprolol in plasma could
      not be satisfactorily employed due to interference from plasma components. Thus,
      an improved, convenient and efficient method for the determination of the plasma
      concentration of celiprolol was developed using a simple solvent extraction step
      followed by high-performance liquid chromatography on a silanol deactivated C18
      column with fluorescence detection. The plasma interference was resolved from
      celiprolol and the typical trailing of basic compounds on reversed-phase HPLC was
      eliminated. The peak-area ratio versus plasma concentration was linear over the
      range of 5-1000 ng/ml and the detection limit was 5 ng/ml.

PMID- 9017474
TI  - IQ variability in children with SLI: implications for use of cognitive
      referencing in determining SLI.
AB  - The practice of cognitive referencing assumes that IQ scores can be used as a
      measure of intellectual potential from which language scores may deviate. To test
      the validity of this assumption the WISC scores of children with specific
      language impairment were compared over time. The variability of WISC scores from
      children with SLI from their initial evaluation and from the federally-mandated
      three year re-evaluation was analyzed. Significant differences in the performance
      scale scores were found. This indicates that the IQ scores of these children are
      more properly interpreted as reflecting current abilities rather than potential
      for language learning. This further calls into question the practice of cognitive
      referencing as a method of determining the presence of a language impairment,
      eligibility for services, and the service delivery model for which a child
      qualifies.

PMID- 9017475
TI  - Diversity of patterns of improvement in confrontation naming rehabilitation: some
      tentative hypotheses.
AB  - A previous group analysis of the effects of a computerized written naming
      rehabilitation program revealed global improvement with generalization of
      benefits to untrained items and to untreated oral naming (Deloche et al., 1992).
      The present multiple single-case analysis of the data indicates a variety of
      patterns of improvement and of generalization effects among individual patients.
      Patterns of relationships between written and oral naming behaviors help to
      explain the type of improvement that was observed.

PMID- 9017476
TI  - Criterion validity of the Language Background Questionnaire: a self-assessment
      instrument.
AB  - The present investigation examined relationships between the Language Background
      Questionnaire (LBQ) self-assessed sign language skills. LBQ self-assessed spoken
      communication skills, and formal independent sign and spoken communication skills
      assessments of young adults who are deaf or hard of hearing. Results indicated a
      high degree of congruence between self-assessed communication skills and formal
      independent assessments of communication skills. The findings establish
      reasonable criterion validity for the LBQ regarding self-assessed sign language
      and spoken communication skills.

PMID- 9017477
TI  - Test-retest reliability of three aphasia tests: performance of non-brain-damaged
      older adults.
AB  - This study was designed to assess the test-retest reliability of three aphasia
      tests. The Auditory Comprehension Test for Sentences (ACTS), the Boston Naming
      Test (BNT), and the Reading Comprehension Battery for Aphasia (RCBA) were
      administered on two separate occasions to 31 non-brain-damaged adults aged 50 to
      76 years. The results showed acceptable score stability for all three aphasia
      tests. Sixty-eight percent of the time, older non-brain-damaged adults would be
      expected to score within 4.0% or less of the total number of test items on
      repeated testing.

PMID- 9017478
TI  - Standardized test performance of children with a history of prenatal exposure to
      multiple drugs/cocaine.
AB  - Twenty-four children, age 14 to 50 months, with a history of prenatal exposure to
      multiple drugs including cocaine, were matched by adjusted birth age and sex to
      24 children with no history of drug exposure. All children had been living in
      stable, drug-free environments from at least the age of 11 months. Tests
      administered included the Sequenced Inventory of Communicative Development
      Revised (SICD), the Bayley Scales of Infant Development, and the Peabody Picture
      Vocabulary Test-Revised (PPVT-R). Results indicated significant differences
      between groups and genders on the SICD when age was covaried and between groups
      on the Bayley. No groups or genders differed on the PPVT-R. Many (45.8%) of the
      children in the drug-exposed group qualified for intervention services according
      to Washington state criteria. Subject characteristics, other than age, did not
      play a significant role in the findings of group differences. It is concluded
      that, due to the cumulative effects of prenatal history, these children should be
      considered at risk for language delay.

PMID- 9017479
TI  - Patient comprehension of doctor-patient communication on discharge from the
      emergency department.
AB  - An exit interview was conducted during March, 1994 on 314 patients treated and
      released from the Emergency Department at Kern Medical Center in Bakersfield,
      California. The questionnaire was designed to assess understanding of diagnosis,
      prescribed medications, additional instructions, and plans for follow-up care.
      The patients' own perceptions of the adequacy of communication and whom they
      considered the most important source of information were also determined.
      Overall, patients correctly identified 59% of their instructions. The performance
      of the English speaking and the Spanish speaking patients was compared. Spanish
      speaking patients scored significantly lower on all questions. The physician was
      identified by most patients (63.8%) as the source of the most information.

PMID- 9017480
TI  - Language as a factor affecting follow-up compliance from the emergency
      department.
AB  - We evaluated language (English vs. Spanish) as a variable in compliance with
      follow-up appointments from emergency department (ED) referrals and compared it
      with four other socioeconomic variables. Patients were interviewed on
      presentation to the ED. A follow-up interview was performed by phone 8 weeks
      later, after the scheduled referral date. We find that language is not a
      significant variable influencing follow-up compliance. Having a primary medical
      doctor prior to the ED visit was positively correlated with follow-up compliance
      and was the only significant socioeconomic variable irrespective of language
      ability. There was no significant correlation between English speaking and any of
      the socioeconomic variables. Among Spanish speakers, having a primary medical
      doctor and having some form of medical insurance were significantly correlated to
      compliance with referrals.

PMID- 9017481
TI  - The efficacy of intravenous droperidol in the prehospital setting.
AB  - Droperidol is used for sedating combative patients in the emergency department
      (ED). We performed a randomized, prospective, double-blind study to evaluate the
      efficacy of droperidol in the management of combative patients in the prehospital
      setting. Forty-six patients intravenously received the contents of 2-cc vials of
      saline or droperidol (5 mg). Paramedics used a 5-point scale to quantify
      agitation levels prior to and 5 and 10 min after administration of the vials.
      Twenty-three patients received droperidol and 23 received saline. At 5 min,
      patients in the droperidol group were significantly less agitated than were
      patients in the saline group. At 10 min, this difference was highly significant.
      Eleven patients in the saline group (48%) required more sedation after arrival in
      the ED versus 3 patients (13%) in the droperidol group. We conclude that
      droperidol is effective in sedating combative patients in the prehospital
      setting.

PMID- 9017482
TI  - Nontraumatic intracranial internal carotid artery dissection: a case report.
AB  - The case presented offers a demonstration of a rare yet devastating condition
      that may go unrecognized and incompletely worked up by the emergency physician.
      Internal carotid artery dissection is seen most often in previously healthy,
      young patients and thus all efforts toward diagnosing this condition and
      providing proper stabilization must be made. Unfortunately, little advancement in
      the therapeutic progress of this frequently fatal condition has been made over
      the past decades. To date, both medical management and surgical techniques have
      been utilized with variable success. This case should serve to remind physicians
      evaluating young patients with stroke symptoms or other neurological findings
      that a negative head CT scan may not be the last test necessary for the
      definitive diagnosis.

PMID- 9017483
TI  - Traumatic carotid cavernous sinus fistula following a gunshot wound to the face.
AB  - A case of a traumatic carotid cavernous sinus fistula following a gunshot wound
      to the face is described. Although its occurrence is rare, the diagnosis can be
      made in the emergency department. The presentation, pathogenesis, and management
      of carotid cavernous sinus fistula are discussed.

PMID- 9017484
TI  - Delayed cardiac tamponade in a patient with penetrating chest trauma.
AB  - We describe a case of cardiac tamponade due to pulmonary artery laceration as a
      late sequela in a patient who had sustained penetrating chest trauma. A 35-yr-old
      man presented to our emergency department complaining of pleuritic left chest
      pain, shortness of breath, and fever 19 days after being hospitalized for a stab
      wound to the left chest. During his first hospitalization, chest X-ray study,
      echocardiogram, and central venous pressure determination were all normal. On
      second presentation, he had a cardiac tamponade and underwent a median
      sternotomy. A pulmonary artery laceration was discovered and repaired. The
      postoperative course was complicated by readmission for postcardiotomy syndrome.
      This case demonstrates that late and unexpected complications can occur in
      patients with penetrating chest trauma and a normal initial evaluation.

PMID- 9017486
TI  - Anorectal fistula: an unusual presentation in a Crohn's disease patient.
AB  - An unusual case of an anorectal fistula presenting with hip pain and extensive
      lower limb muscle wasting in a patient with Crohn's disease is reported. This
      report emphasizes the important role of a thorough history, a complete physical
      examination, and a thorough search for evaluating such cases. Any progressive
      local irritation and pain in a Crohn's disease patient may indicate possible
      fistulous involvement. Nonspecific laboratory findings such as leukocytosis,
      anemia, decreased albumin level, and thrombocytosis may be considered as
      supportive indicators. Barium contrast studies and enhanced computed tomography
      scan may be helpful but can be falsely negative in the presence of a fistula, as
      in this case. These findings illustrate that the clinician must not be dissuaded
      from the diagnosis simply based on negative radiological findings because the
      presence of a fistula may be impossible to determine preoperatively.

PMID- 9017485
TI  - Pheochromocytoma and bowel ischemia.
AB  - This case report presents a patient with an adrenal pheochromocytoma manifesting
      as intestinal ischemia. Emergency department and hospital courses are described.
      Complications of pheochromocytoma are briefly reviewed, with special reference to
      the gastrointestinal findings in this syndrome. The onset of gastrointestinal
      symptoms in patients with pheochromocytoma can be a herald of intestinal
      ischemia, necessitating prompt medical and surgical intervention.

PMID- 9017487
TI  - Accidental hypothermia: a potential life-threatening hazard of automobile
      platform lifts.
AB  - The wheelchair/scooter of a patient with a relapsing-remitting form of multiple
      sclerosis was immobilized after inadvertent slippage of the rear wheels of his
      scooter off an automobile platform lift during travel. While waiting 45 min for
      the rescue squad, he developed mild hypothermia that responded to passive
      external rewarming techniques. This potentially life-threatening injury could
      have been prevented by using a platform lift equipped with full inboard and
      outboard roll-stop barriers on the platform.

PMID- 9017488
TI  - Emergency department approach to acute thoracolumbar spine injury.
AB  - This review provides a literature-based approach to the management of acute
      thoracolumbar spine (TLS) injury. The epidemiology of spinal cord injury and
      pertinent spinal cord anatomy are reviewed. A review of current TLS
      fracture/dislocation classification schemes is provided. The principal focus of
      this review is the immediate diagnostic and therapeutic interventions needed to
      maximize the recovery of patients with acute TLS injury.

PMID- 9017489
TI  - Acute intravaginal misoprostol toxicity with fetal demise.
AB  - We report a case of an overdose with fetal demise from the intravaginal
      administration of misoprostol. A 25-yr-old gravid female self-administered 6000
      micrograms misoprostol intravaginally and 600 micrograms orally. She rapidly
      developed shaking chills, abdominal and extremity cramping, emesis, and
      confusion. Hyperthermia and hypotension developed within 3.5 h after drug
      administration, with a temperature of 41.4 degrees C (106 degrees F). Ultrasound
      at 3.5 h after drug administration showed no fetal movement or heart motion. A
      nonviable fetus was delivered by emergent cesarean section. Treatment of the
      mother was supportive and included intravaginal decontamination and endotracheal
      intubation with neuroparalytic therapy to control agitation and hyperthermia.
      Recovery was complete within 15 h of drug administration.

PMID- 9017490
TI  - Anticholinergic toxicity from nightshade berry poisoning responsive to
      physostigmine.
AB  - The woody nightshade, Solanum dulcamara, belongs to the genus Solanum and its
      primary toxin is solanine. We report a large nightshade ingestion in a 4-yr-old
      girl who presented to the emergency department in acute anticholinergic crisis.
      The child was given 0.2 mg of intravenous physostigmine (0.02 mg/kg). Within 50
      min, the patient received two additional equal doses with complete resolution of
      symptoms. After 36 h of observation, the child was discharged. Our patient
      presented with symptoms more suggestive of the deadly nightshade species, Atropa
      belladonna, which is native to Europe; however, a detailed laboratory analysis of
      the suspect berries revealed no atropine or hyoscyamine. Analysis did reveal
      sterols consistent with solanine. This is a unique case presentation of woody
      nightshade, S. dulcamara, poisoning presenting with anticholinergic crisis and
      responding to physostigmine.

PMID- 9017491
TI  - Natural rubber latex allergy: spectrum, diagnostic approach, and therapy.
AB  - Latex allergy has reached epidemic proportions in the United States and is
      increasingly recognized as a significant contributor to morbidity and mortality
      during medical and surgical procedures. Ultimately, many of the affected patients
      with recognized latex sensitivity and those who are not yet diagnosed will
      receive treatment for their allergic reactions to latex in emergency departments.
      Consequently, emergency physicians must have a comprehensive understanding of the
      etiology, epidemiology, pathogenesis, treatment, and management of these
      challenging patients. Groups at high risk include spina bifida cystica patients,
      health care workers, latex industry workers, specific food-allergy patients, and
      patients with a history of atopy or multiple surgical procedures. Sensitization
      to latex antigens is commonly encountered in health care workers wearing latex
      gloves with high latex allergen concentrations and in workers using powdered
      latex surgical gloves. Exposure to air-borne allergens and water-soluble IgE
      reactive latex antigens from natural rubber latex products in sensitized
      individuals can result in type I (immediate) hypersensitivity reactions. Clinical
      manifestations include contact urticaria, dermatitis, allergic rhinitis,
      conjunctivitis, asthma, angioedema, and anaphylaxis. Diagnostic tools include
      serological assays and skin prick testing. At present, latex avoidance is the
      only available treatment and is the key to preventing allergic reactions in latex
      sensitized individuals. Health care worker sensitization to latex antigens in
      natural rubber products is becoming an increasing contributor to workers'
      liability and disability claims. Specific action can be taken to reduce
      occupational and patient exposure to latex antigens.

PMID- 9017492
TI  - Status asthmaticus in a paramedic following exposure to a roadside flare: a case
      report.
AB  - Highway flares are commonly used by police and emergency service workers to
      divert traffic away from roadside accidents. We report a case of a 35-yr-old
      paramedic who developed a sudden, severe asthmatic reaction following a brief
      exposure to such a flare, necessitating intubation and a prolonged
      hospitalization.

PMID- 9017493
TI  - Transcutaneous cricolaryngeal illumination as an adjunct during orotracheal
      intubation.
AB  - Transcutaneous cricolaryngeal illumination is an adjunct visualization technique
      that is useful during orotracheal intubation. A pilot study demonstrated that
      light from an external high-intensity cool-light source applied to the anterior
      neck, over the cricothyroid membrane, resulted in transillumination of the
      glottis in 70% of patients and provided enhanced laryngoscopic visualization of
      anatomic structures during oral endotracheal tube placement.

PMID- 9017494
TI  - Altered mental status in an anticoagulated patient.

PMID- 9017495
TI  - Supracondylar fracture.

PMID- 9017496
TI  - The princes and princesses of possibilities.

PMID- 9017497
TI  - Do fireservice paramedics (EMT-P) seek follow-up medical information about
      patients brought to a level I trauma center?

PMID- 9017498
TI  - An analysis of dilemmas posed by prehospital DNR orders.
AB  - This article briefly recounts the development of the prehospital do-not
      resuscitate (DNR) order and indicates certain situations, such as a choking
      episode or a suicide attempt, in which the presence of a DNR order may provoke a
      moral dilemma for the emergency medical technician as to whether or not the
      patient should be treated. An ethical analysis of this question is performed and
      concludes that resuscitative treatment is ethical and mandatory.

PMID- 9017499
TI  - Waiting for the plumber.

PMID- 9017500
TI  - Outpatient treatment of spontaneous pneumothorax in a community hospital using a
      Heimlich flutter valve: a case series.
AB  - This is a case series of 14 consecutive patients treated as outpatients for
      spontaneous pneumothorax (SP) (1 January 1992 to 31 December 1995) by one surgeon
      in a community hospital setting. The purpose of this study was to examine the
      appropriateness and financial implications of routine outpatient management of SP
      with closed tube thoracostomy and the Heimlich valve. All 14 patients reviewed
      were successfully managed as outpatients, although 3 required an overnight
      admission because of anxiety, pain, or vasovagal reaction. The routine outpatient
      treatment of all cases of SP not requiring definitive surgical intervention may
      have saved more than $16,000.00 for the hospital and an estimated $500,000.00 for
      the province of Ontario during the 1993-1994 fiscal year. Our findings suggest
      that the Heimlich valve is an appropriate alternative for the management of SP in
      a nonteaching community hospital setting, with benefits to the patient and to the
      health care system.

PMID- 9017501
TI  - Apolipoprotein-mediated removal of cellular cholesterol and phospholipids.
AB  - It is widely believed that high density lipoprotein (HDL) protects against
      cardiovascular disease by removing excess cholesterol from cells of the artery
      wall. Recent cell culture studies have provided evidence that a major pathway for
      removing cholesterol and phospholipids from cells is mediated by the direct
      interactions of HDL apolipoproteins (apo) with plasma membrane domains. These
      interactions efficiently clear cells of excess sterol by targeting for removal
      pools of cholesterol that feed into the cholesteryl ester cycle. The precursors
      for this pathway in vivo are likely to be lipid-free or lipid-poor
      apolipoproteins generated either by dissociation from the surface of HDL
      particles or by de novo synthesis. Fibroblasts from subjects with a severe HDL
      deficiency syndrome called Tangier disease have a cellular defect that prevents
      apolipoproteins from removing both cholesterol and phospholipids from cells. This
      defect is associated with a near absence of plasma HDL, markedly below normal low
      density lipoprotein (LDL) levels, and the appearance of macrophage foam cells in
      tissues. Thus, an inability of nascent apoA-I to acquire cellular lipids results
      in a rapid clearance of apoA-I from the plasma, decreased production and
      increased clearance of LDL, and sterol deposition in tissue macrophages. Although
      the molecular properties of this pathway are still poorly understood, these
      studies imply that the apolipoprotein-mediated pathway for removal of cellular
      lipids is a major source of plasma cholesterol and phospholipids and plays an
      important role in clearing excess cholesterol from macrophages in vivo.

PMID- 9017502
TI  - Decreases in retinol and retinol-binding protein during total parenteral
      nutrition in rats are not due to a vitamin A deficiency.
AB  - Perfusion feeding in rats induced a decrease in circulating retinol despite an
      adequate supply of vitamin A. We studied the effect of total parenteral nutrition
      (TPN) on the retinol specific carrier in rat, analyzing holo-RBP (bound to
      retinol) and apo-RBP (without retinol) in serum and in liver. Vitamin A
      sufficient (A+) and -deficient (A-) rats were characterized in terms of vitamin A
      and RBP status and then perfused (TPN-A+ and TPN-A-) or orally pair-fed (O-A+ and
      O-A-) with vitamin A. In A+ rats, a decrease in serum retinol (2.6-fold) and an
      increase in apo-RBP was concomitant with a massive accumulation of RBP in the
      liver. In TPN-A rats, both circulating RBP and liver total RBP were decreased. In
      TPN-A+ rats, there was a decrease in circulating retinol (2.4-fold) in parallel
      to a decrease of serum and liver RBP protein and mRNA. We provide evidence that
      infused retinyl palmitate was not responsible for serum retinol and RBP decrease
      and that retinol depletion was not due to vitamin A deficiency. Whatever the
      vitamin A status, TPN may induce in rats a down-regulation of hepatic RBP
      synthesis, which may, at least partially, explain the alteration of retinol and
      RBP in serum.

PMID- 9017503
TI  - Tissue-specific coordinate regulation of enzymes of cholesterol biosynthesis:
      sciatic nerve versus liver.
AB  - Exposure of weanling rats to a diet containing the element tellurium results in
      specific inhibition of squalene epoxidase, an obligate enzyme in cholesterol
      biosynthesis. Liver responds to the resulting intracellular sterol deficit by up
      regulating, in parallel and to the same extent, expression of mRNA for squalene
      epoxidase and for HMG-CoA reductase, the major rate-limiting enzyme in the
      pathway. This increased mRNA expression, coupled with additional translational
      and posttranslational activation of the pathway allows normal levels of
      cholesterol synthesis in liver despite tellurium-induced inhibition of squalene
      epoxidase. The response to tellurium challenge in sciatic nerve is very
      different. In this tissue, cholesterol synthesis is prominent because of the
      large amount of cholesterol required for synthesis and maintenance of myelin.
      Although nerve shows an initial (at 1 day) up-regulation of mRNA expression for
      both enzymes in response to tellurium exposure, this is followed quickly by
      parallel down-regulation of both enzymes, in concert with down-regulation of mRNA
      expression for myelin proteins. We suggest that the tellurium-induced deficit in
      sterols leads to a coordinate down-regulation of synthesis of myelin components.
      The initial early up-regulation of cholesterol biosynthesis in sciatic nerve due
      to the cholesterol deficit is countered by down-regulation which is coordinated
      with overall control of the program of myelin assembly. This tissue-specific
      control of cholesterol synthesis in sciatic nerve is a point of vulnerability to
      toxicants, and may be related to the need for coordinate synthesis of all
      components of myelin.

PMID- 9017504
TI  - Apolipoprotein-mediated cellular cholesterol and phospholipid efflux depend on a
      functional Golgi apparatus.
AB  - Several studies have demonstrated that lipid-free apolipoproteins can promote
      cholesterol and phospholipid efflux from cells; however, the mechanisms and the
      role of cell-mediated pathways involved remain incompletely elucidated. We have
      recently demonstrated that brefeldin A or monensin, agents that disrupt Golgi
      apparatus structure and function, inhibit intracellular cholesterol efflux from
      cells to high density lipoproteins. In the present study we examined the effects
      of those agents on cell cholesterol and phospholipid efflux to purified
      apolipoprotein A-I (apoA-I) and apolipoprotein-depleted acceptors from
      cholesterol-loaded fibroblasts. Brefeldin A or monensin treatment of cells during
      incubation with apoA-I inhibited efflux of cellular cholesterol by greater than
      80% compared with control cells, measured by changes in cellular cholesterol
      radioactivity, mass, and the substrate pool of cholesterol available for
      esterification by acyl coenzyme A:cholesterol acyltransferase. Inhibition of
      cholesterol efflux by these agents could not be overcome by increasing the apoA-I
      concentration and persisted during incubations up to 24 h. Similarly, brefeldin A
      and monensin inhibited up to 80% of apoA-I-mediated efflux of labeled
      phospholipids from cholesterol-loaded cells relative to controls. In contrast,
      lipid efflux mediated by apolipoprotein-depleted acceptors (trypsin-modified HDL
      and sonicated phospholipid vesicles) was not sensitive to these drugs. On the
      basis the known effects of brefeldin A and monensin on Golgi apparatus structure
      and function, these results are consistent with the notion that efflux of cell
      lipids by apolipoprotein-dependent mechanisms, but not by apolipoprotein
      independent mechanisms, require active cellular processes involving an intact and
      functional Golgi apparatus.

PMID- 9017505
TI  - In situ assay of acid sphingomyelinase and ceramidase based on LDL-mediated
      lysosomal targeting of ceramide-labeled sphingomyelin.
AB  - The activity of lysosomal sphingolipid hydrolases is usually estimated in vitro
      from complex assays on cell lysates under artificial conditions including the
      presence of detergents and substrate analogs. However, the measure of their
      effective activity in situ (i.e., in living cells) is necessary to understand the
      normal intracellular sphingolipid turnover. Moreover, their determination in
      cells from patients with genetic enzyme deficiencies represents a key parameter
      of the pathophysiology of sphingolipid storage disorders. In this report, we have
      developed a procedure for estimating the effective activity of lysosomal
      sphingomyelinase and ceramidase in situ. This procedure is based on the selective
      targeting to lysosomes of a natural substrate under physiological conditions of
      substrate influx. Epstein-Barr virus-transformed human lymphoid cells and human
      skin fibroblasts were incubated with purified human low density lipoproteins
      (LDL) containing [3H]ceramide-labeled sphingomyelin. Data demonstrate that this
      substrate is internalized through the apolipoprotein B/E receptor pathway and
      targeted to lysosomes. Lysosomal localization of the incorporated substrate was
      evidenced by ultrastructural autoradiography and subcellular fractionation as
      well as by metabolic studies in mutant cells. Short-term pulse-chase experiments
      with LDL-associated [3H]ceramide-labeled sphingomyelin allowed us to determine
      the effective activity of lysosomal sphingomyelinase and ceramidase in normal
      cells. Initial velocities of sphingomyelin and ceramide degradation were,
      respectively, estimated at 0.66 and 1.14 nmol.h-1.mg cell protein-1 in lymphoid
      cells, and 5.4 and 3 nmol.h-1.mg cell protein-1 in skin fibroblasts. The
      advantages and applications of these in situ studies are discussed.

PMID- 9017506
TI  - Characterization of crystallization pathways during cholesterol precipitation
      from human gallbladder biles: identical pathways to corresponding model biles
      with three predominating sequences.
AB  - In model biles, five crystallization sequences are present as functions of bile
      salt/lecithin (egg yolk) ratio and their positions on phase diagrams are
      influenced by bile salt hydrophobicity, temperature, and total lipid
      concentration (D. Q-H. Wang and M.C. Carey. J. Lipid Res. 1996.37: 606-630). To
      determine whether the same pathways occur ex vivo during cholesterol
      precipitation from human gallbladder biles, we examined 22 cholesterol gallstone
      (CSI = 1.56 +/- 0.26), 4 pigment gallstone (0.69 +/- 0.06), and 4 control biles
      (0.85 +/- 0.22) by microscopy and lipid analytic techniques for 30 days.
      Temperature was varied (4-45 degrees C) to move relative compositions into
      adjacent pathways or supersaturated zones to test whether the same bile could be
      forced to crystallize in different sequences. Sequences in native bile were
      identical to those in model systems composed of mixed bile salts-lecithin
      cholesterol mixtures, and three corresponding pathways (B, C, D; op. cit.) were
      observed at 37 degrees C. With increasing lecithin content, we found i) B: plate
      like cholesterol monohydrate crystals appeared before arc-shaped (putatively
      anhydrous cholesterol) crystals which transformed via helices and tubules into
      plate-like crystals and no liquid crystals formed; ii) C: lamellar liquid
      crystals, typified by birefringent multilamellar vesicles, were detected before
      cholesterol monohydrate crystals, and subsequently arc, helical and tubular
      crystals appeared; and iii) D: precipitation of lamellar liquid crystals was
      followed by cholesterol monohydrate crystals and no arc crystals were detected.
      Added EDTA prevented calcium bilirubinate formation, but crystallization
      sequences in these biles were identical to those without EDTA. We conclude that
      i) cholesterol crystallization pathways and sequences in human gallbladder biles
      are identical to model biles matched for appropriate physical-chemical
      conditions; ii) three of the five sequences observed in model biles were found in
      native bile; and iii) calcium bilirubinates neither promote biliary cholesterol
      crystallization nor influence crystal growth.

PMID- 9017507
TI  - Comparison of side chain oxidation of potential C27-bile acid intermediates
      between mitochondria and peroxisomes of the rat liver: presence of beta-oxidation
      activity for bile acid biosynthesis in mitochondria.
AB  - The oxidation of the side chains of two potential bile acid intermediates, 3
      alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) and 3 alpha,7
      alpha-dihydroxy-5 beta-cholestanoic acid (DHCA), were investigated in rat liver
      mitochondria and peroxisomes. Both THCA and DHCA were efficiently oxidized to
      yield cholic acid and chenodeoxycholic acid, along with 3 alpha,7 alpha,12 alpha
      trihydroxy-5 beta-cholest-24-enoic acid and 3 alpha,7 alpha-dihydroxy-5 beta
      cholest-24-enoic acid, respectively, in both the mitochondria and peroxisomes.
      However, the spectrum of the metabolites in the mitochondria differed greatly
      from those in the peroxisomes. The major products from THCA and DHCA in the
      mitochondria were 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-chol-22-enoic acid
      and 3 alpha,7 alpha-trihydroxy-5 beta-chol-22-enoic acid, respectively, which
      were tentatively identified from the mass spectral data. However, the formation
      of these C24-unsaturated bile acids was not observed in the peroxisomes. These
      results strongly suggest that the cleavage of the side chain of the C27
      intermediates for bile acid biosynthesis also occurs independently in the
      mitochondria, not due to the contamination of peroxisomes.

PMID- 9017508
TI  - Localization of apolipoprotein A-I epitopes involved in the activation of
      lecithin:cholesterol acyltransferase.
AB  - Eight murine monoclonal antibodies (Mab) to apolipoprotein A-I were characterized
      for their epitopes and for their ability to interfere with lecithin:cholesterol
      acyltransferase (LCAT) activation mediated by apo apoA-I using a synthetic
      substrate. Using overlapping synthetic peptides we have identified six continuous
      epitopes that span amino acids 1-10 (Mab A-I-19), 96-101 (Mab A-I-15), 133-141
      (Mab A-I-5), 140-145 (Mab A-I-9), 144-148 (Mab A-I-8), and 167-174 (Mab A-I-57).
      Furthermore, antibodies A-I-11 and A-I-16 recognized discontinuous epitopes,
      namely amino acids 124-128 and 144-148. When antibodies were tested for their
      ability to inhibit LCAT activation, an inhibitory effect was observed with those
      whose epitopes covered the area of apoA-I encompassing amino acids 96-174. From
      these data we conclude that several areas of apoA-I spanning the middle region of
      the apolipoprotein act in concert to stimulate LCAT activity, possibly by
      cooperative interaction with the enzyme.

PMID- 9017509
TI  - Differences in Lp[a] concentrations and apo[a] polymorphs between black and white
      Americans.
AB  - Lp[a] concentrations in nmol/L and apo[a] size isoforms, expressed in terms of
      the relative number of apo[a] kringle 4 (K4) repeats, were determined in 3959
      whites and blacks from four U.S. communities. Plasma Lp[a] analyses were
      performed by an ELISA method insensitive to apo[a] size heterogeneity and apo[a]
      size isoforms were determined by high resolution agarose gel electrophoresis.
      Allele frequencies were estimated by maximum likelihood methods in order to
      account for the presence of null alleles and coalescence of hands on gels. The
      apo[a] allele frequencies and phenotype distributions differed significantly
      between blacks and whites (P < 0.0001). Blacks had a higher relative frequency of
      the intermediate alleles K4(22) through K4(28) whereas whites had a higher
      relative frequency of the small alleles K4(17) through K4(24) and large alleles
      K4(29) through K4(33). The estimated frequency of the null allele was low in both
      blacks (1.0%) and whites (6.7%). The Lp[a] distribution was less skewed and Lp[a]
      concentrations were higher in blacks than whites (mean 94 nmol/L and 48 nmol/L,
      median 74 nmol/L and 20 nmol/L for blacks and whites, respectively). The
      relationship between apo[a] size and Lp[a] concentration also differed
      significantly between these two racial groups. For the large polymorphs (> 31 K4
      repeats) both blacks and whites exhibited uniformly low Lp[a] values. For the
      intermediate isoforms K4(20) through K4(30), a considerable range of Lp[a] values
      was evident in blacks; the median Lp[a] for each isoform increased nearly
      linearly as the apo[a] size decreased. In contrast in whites there was little
      change in median Lp[a] concentrations for isoforms K4(20) through K4(30). For the
      small apo[a] size (< 20 K4) both blacks and whites exhibited high median Lp[a]
      levels and a wide variation of Lp[a] levels. The major difference in Lp[a] levels
      between the two racial groups occurred in the intermediate size isoform range of
      K4(20) through K4(25). In conclusion, whites and blacks differ significantly in
      Lp[a] concentrations, allele and phenotype frequencies, and in the relationship
      between apo[a] size isoform and Lp[a] concentration.

PMID- 9017510
TI  - LY295427, a novel hypocholesterolemic agent, enhances [3H]25-hydroxycholesterol
      binding to liver cytosolic proteins.
AB  - LY295427, (3 alpha,4 alpha,5 alpha)-4-(2-propenylcholestan-3-ol), acts through an
      unknown mechanism to derepress the transcription of the low density lipoprotein
      (LDL) receptor in the presence of 25-hydroxycholesterol (25-OH chol).
      Preincubation with LY295427 in Chinese hamster ovary (CHO) cells increased uptake
      of 25-OH chol in a time-dependent manner, suggesting that the drug interfered
      with the negative feedback mechanism of 25-OH chol on LDL receptor expression. To
      explore the mechanism by which LY295427 inhibited the suppressive actions of 25
      OH chol, the radioactive ligand [3H]25-OH chol and specific antibodies to the
      oxysterol binding protein (OSBP) were used to identify possible drug:protein
      interactions. After separation by anion exchange chromatography, protein
      fractions from hamster liver cytosol were found to selectively bind [3H]25-OH
      chol with high affinity. In fractions in which 25-OH chol binding was evident,
      and in other distinct fractions that lacked specific binding, addition of
      LY295427 increased [3H]25-OH chol binding 2- to 5-fold. LY306039, the 3 beta
      isomer of LY295427, failed to derepress the LDL receptor in CHO cells, and it had
      no effect on [3H]25-OH chol binding. Analysis of Western blots using polyclonal
      antibodies to OSBP showed that specific [3H]25-OH chol binding in the absence of
      LY295427 was present only in fractions containing OSBP. However, enhanced [3H]25
      OH chol binding in the presence of LY295427 was evident in distinct fractions
      after immunodepletion of both the 90-100 kDa form of OSBP and a 170 kDa protein;
      and specific binding of a radioiodinated analog of LY295427 was detected in
      select fractions lacking [3H]25-OH chol binding in the absence of LY295427.
      Moreover, LY295427 did not displace or enhance [3H]25-OH chol binding to OSBP
      purified to near homogeneity. These data suggest that LY295427, while not
      dependent on the presence of oxysterol binding protein, binds to cytosolic
      protein(s) that interact with 25-hydroxycholesterol and other oxystcrols, thus
      preventing the repression of the LDL receptor.

PMID- 9017511
TI  - A single nucleotide substitution in the promoter region of the apolipoprotein C
      II gene identified in individuals with chylomicronemia.
AB  - Apolipoprotein (apo) C-II plays a major role as a cofactor for lipoprotein
      lipase, the enzyme involved in the hydrolysis of triglyceride-rich particles. We
      identified in two relatives of a family (mother and son) massive
      hypertriglyceridemia with chylomicronemia. In these individuals apoC-II was not
      measurable in plasma by radial immunodiffusion. On isoelectric focusing of very
      low density apolipoproteins, trace amounts of apoC-II became obvious in the
      regular position. By sequencing, no abnormalities in the exons or neighboring
      intron sequences were detected. However, three alterations in the DNA sequence
      were found upstream from the transcription initiation site. Two variations could
      be explained by differences in previously published DNA sequences. The third
      variation (A-->G; position -86; Das et al. 1987. J. Biol. Chem. 262: 4787-4793)
      was present only in the homozygous form in the two hypertriglyceridemic probands.
      In 46 hypertriglyceridemic individuals outside the family, this mutation was not
      found. In electrophoretic mobility shift experiments with nuclear extracts from
      HepG2 cells, the 31 bp DNA fragment carrying the A-->G substitution resulted in a
      markedly diminished protein binding compared with the wildtype DNA fragment. In
      promoter reporter gene assays, the activity of the basal promoter was reduced in
      the case of the A-->G substitution and the deletion of the bases -91 to -58. The
      pedigree analysis and the experimental results are evidence that this is the
      first mutation in the apolipoprotein C-II gene where a single nucleotide
      substitution diminishes the binding of a transcription factor to a positive cis
      acting clement in the promoter resulting in a depletion of apolipoprotein C-II in
      plasma.

PMID- 9017512
TI  - Identification of short-chain oxidized phosphatidylcholine in human plasma.
AB  - Oxidized phospholipids have been recognized as potentially important compounds
      that carry biological activities similar to the platelet-activating factor, but
      their presence in biological tissue has not been firmly established. We developed
      a novel technique for the quantitative analysis of phospholipids with oxidized
      acyl chains. The method involves 1) lipid extraction, 2) chromatographic
      enrichment of phospholipids with short acyl chains, 3) derivatization with 9
      (chloromethyl)anthracene, 4) solid-phase extraction of the derivatives, and 5)
      reversed-phase HPLC with fluorescence detection. The technique was capable of
      measuring dicarboxylate-containing phosphatidylcholines (PCs) at the picomole
      level. The method was suited to monitor the generation of oxidized phospholipids
      from 1-palmitoyl-2-arachidonoyl-PC in the presence of Fe21/ascorbate. The new
      procedure was used to isolate lipids from human plasma that were identified as
      anthracene derivatives of short-chain oxidized PC on the basis of chromatographic
      enzymatic, and spectroscopic evidence. The plasma concentration, determined with
      an internal standard (1-palmitoyl-2-suberoyl-PC), was 0.6 +/- 0.2 microM (n =
      11). The analytical method did not produce oxidation antifacts in significant
      amount. We concluded that human blood contains oxidatively fragmented PC in
      submicromolar concentration.

PMID- 9017513
TI  - Evidence of two catalytically active carnitine medium/long chain acyltransferases
      in rat liver peroxisomes.
AB  - Peroxisomal matrix proteins were extracted from the highly purified peroxisomes
      with sodium pyrophosphate, and the membranes were sedimented by high speed
      centrifugation. Biochemical marker enzyme analyses revealed a quantitative
      release of a number of well-known peroxisomal matrix proteins from the purified
      peroxisomes. In contrast, carnitine medium/long chain acyltransferase activity,
      assayed with decanoyl-CoA and palmitoyl-CoA as substrates, was equally
      distributed in the membrane and the matrix fractions. The matrix and the membrane
      enzyme activities were differentially affected by a number of detergents. The
      enzyme in the membrane fraction showed higher malonyl-CoA sensitivity compared to
      the enzyme in the matrix fraction. The enzyme(s) from the purified peroxisomes or
      the peroxisomal membranes was quantitatively solubilized by sodium cholate, and
      the cholate-solubilized enzyme retained malonyl-CoA sensitivity. The membrane
      enzyme was separated from the matrix enzyme by hydroxylapatite column
      chromatography. The separation of the membrane enzyme or the matrix enzyme by
      hydroxylapatite column chromatography resulted in loss of malonyl-CoA
      sensitivity. The partially purified membrane and the matrix enzymes showed broad
      substrate specificity, and the highest enzyme activities for both were observed
      with decanoyl-CoA. In contrast to the matrix enzyme, the membrane enzyme was
      strongly inhibited by high concentrations (> or = 50 microM) of acyl-CoAs (> 10
      carbons in length). The matrix enzyme showed a 2.5-fold lower Km for carnitine
      compared to the membrane enzyme. The catalytic properties of the partially
      purified matrix enzyme appear to be similar to the well-characterized peroxisomal
      carnitine octanoyltransferase, though we find highest activity with decanoyl-CoA
      rather than octanoyl-CoA as a substrate. The data presented clearly indicate that
      the membrane and the matrix enzyme activities are due to different proteins.

PMID- 9017514
TI  - Regulatory mutations in the human lipoprotein lipase gene in patients with
      familial combined hyperlipidemia and coronary artery disease.
AB  - We previously reported a compound heterozygote [T(-39)C/T(-93)G] in the human
      lipoprotein lipase (LPL) gene promoter in one out of 19 patients with familial
      combined hyperlipidemia (FCHL) and reduced post-heparin plasma LPL levels. The T(
      39)C substitution resulted in 85% decrease in LPL promoter activity. Further
      screening of Caucasian patients with FCHL, coronary artery disease (CAD), and of
      unselected Caucasian subjects revealed four additional LPL promoter variants.
      Among the same 19 FCHL patients with reduced LPL levels, we found one
      heterozygote for a G(-53)C substitution. Among 115 CAD patients, we found five
      heterozygotes and one homozygote for the T(-93)G substitution and one
      heterozygote for a CC insertion between +13 and +19 of the 5' untranslated
      region. In a group of 183 unselected subjects, three heterozygotes with the T(
      93)G substitution were found. The G(-53)C substitution led to approximately 70
      75% decrease in promoter activity as assayed by transient transfections of THP-1
      (macrophage-like) and C2C12 (myotube-like) cells. The T(-93)G substitution
      resulted in reduction of promoter activity by approximately 40-50%. The CC
      insertion between +13 and +19 caused a decrease in promoter activity by 20% in
      THP-1 and 50% in C2C12. Substitutions at -79 and -95, which had no effect on
      promoter function, were also discovered in the population samples studied. The
      finding of two promoter mutations (-39 and -53) among 19 FCHL patients with
      diminished LPL, but not among the other groups of subjects, suggests a potential
      role of regulatory mutations of the LPL gene in the development of dyslipidemia
      in FCHL.

PMID- 9017515
TI  - Aggregation and fusion of modified low density lipoprotein.
AB  - In atherogenesis, low density lipoprotein (LDL, diameter 22 nm) accumulates in
      the extracellular space of the arterial intima in the form of aggregates of lipid
      droplets (droplet diameter up to 400 nm). Here we studied the effects of various
      established in vitro LDL modifications on LDL aggregation and fusion. LDL was
      subjected to vortexing, oxidation by copper ions, proteolysis by alpha
      chymotrypsin, lipolysis by sphingomyelinase, and nonenzymatic glycosylation, and
      was induced to form adducts with malondialdehyde or complexes with anti-apoB-100
      antibodies. To assess the amount of enlarged LDL-derived structures formed (due
      to aggregation or fusion), we measured the turbidity of solutions containing
      modified LDL, and quantified the proportion of modified LDL that 1) sedimented at
      low-speed centrifugation (14,000 g), 2) floated at an increased rate at high
      speed centrifugation (rate zonal flotation at 285,000 gmax), 3) were excluded in
      size-exclusion column chromatography (exclusion limit 40 MDa), or 4) failed to
      enter into 0.5%. Fast Lane agarose gel during electrophoresis. To detect whether
      particle fusion had contributed to the formation of the enlarged LDL-derived
      structures, particle morphology was examined using negative staining and thin
      section transmission electron microscopy. We found that 1) aggregation was
      induced by the formation of LDL-antibody complexes, malondialdehyde treatment,
      and glycosylation of LDL; 2) fusion of LDL was induced by proteolysis of LDL by
      alpha-chymotrypsin; and 3) aggregation and fusion of LDL were induced by
      vortexing, oxidation by copper ions, and lipolysis by sphingomyclinase of LDL.
      The various modifications of LDL differed in their ability to induce aggregation
      and fusion.

PMID- 9017516
TI  - Oxidation of LDL by recombinant human 15-lipoxygenase: evidence for alpha
      tocopherol-dependent oxidation of esterified core and surface lipids.
AB  - Various lipoxygenases (LO) oxidize low density lipoprotein (LDL) in vitro and 15
      LO has been implicated in the development of atherosclerosis in vivo. Direct
      oxidation of phospholipids (PL) and cholesteryl esters (CE) by LO has been
      proposed as a mechanism whereby these enzymes cause or contribute to LDL lipid
      peroxidation. Herein we show that the extent to which recombinant human 15-LO
      (rhLO) caused peroxidation of LDL's esterified core and surface lipids depended
      on, and directly related to, the alpha-tocopherol (alpha-TOH) content of the
      lipoprotein. Thus, CE and PL of in vivo alpha-TOH-depleted LDL, isolated from a
      patient with familial isolated vitamin E deficiency, were resistant to oxidation
      by rhLO, whereas those in alpha-TOH-containing LDL from the same patient
      receiving vitamin E supplements readily oxidized. The extent to which rhLO caused
      oxidation of CE and PL directly and linearly correlated with LDL's content of
      vitamin E, as demonstrated by studies with in vitro alpha-TOH-depleted
      lipoproteins. The geometric isomers of oxidized cholesteryl linoleate formed in
      LDL during oxidation initiated by rhLO, matched those obtained during non
      enzymic, peroxyl radical-initiated oxidation of LDL whilst alpha-TOH was present.
      Ascorbate, an efficient co-antioxidant for alpha-TOH, completely prevented rhLO
      initiated oxidation of LDL's CE, but did not inhibit rhLO-mediated oxidation of
      unesterified linoleate. These results are inconsistent with direct oxidation of
      LDL esterified lipids by rhLO. Isolated LDL contained free fatty acids (FFA), and
      its exposure to rhLO caused a rapid formation of linoleate hydroperoxide. To
      reconcile these data, we propose that during rhLO-initiated oxidation of LDL,
      enzymic oxidation of FFA preceeds the oxidation of CE and PL, which occurs
      largely via a tocopherol-dependent process.

PMID- 9017517
TI  - HDL content and composition in acute phase response in three species:
      triglyceride enrichment of HDL a factor in its decrease.
AB  - High density lipoprotein (HDL) levels decrease during the acute phase response
      (APR). We have used the APR model of rabbit, baboon, and mouse to study the
      factors that influence HDL level. In the baboons and rabbits there was massive
      hypertriglyceridemia, triglyceride enrichment of HDL (60-80% of core lipids),
      decreases of HDL-cholesterol and apolipoprotein (apo)A-I (to 10% of baseline),
      and increases of apoA-I in the non-lipoprotein bottom fraction suggesting
      dissociation of apoA-I from the particles. Detailed analyses of serum amyloid A
      (SAA)-rich HDL done in the rabbit revealed large, triglyceride-enriched (> 60% of
      core lipids) particles containing > 95% SAA. These particles had a high surface
      to core ratio (13.4 +/- 1.94, control = 3.0 +/- 0.12) and a very high protein
      (79.71 +/- 5.25 weight %, control = 37.2 +/- 0.43) proportion, large (r = 5.95
      nm) when examined by non-denaturing gradient electrophoresis but small when
      examined by electron microscopy (r = 4.2 nm). In the mouse there was no
      hypertriglyceridemia, no triglyceride enrichment of HDL, no decrease of HDL
      cholesterol. ApoA-I decreased to about 61.4% of baseline but did not increase in
      the bottom fraction although large but dense SAA-enriched HDL particles were also
      produced. These results suggest that hypertriglyceridemia, triglyceride
      enrichment of HDL, and dissociation of apoA-I from the particles, possibly by
      displacement of apoA-I by SAA, are important factors in the decline of HDL during
      the APR. Whether differences in triglyceride metabolism account for the
      differences in the HDL response in the species studied requires further
      experimentation.

PMID- 9017518
TI  - Linoleate, alpha-linolenate, and docosahexaenoate recycling into saturated and
      monounsaturated fatty acids is a major pathway in pregnant or lactating adults
      and fetal or infant rhesus monkeys.
AB  - Carbon recycling and desaturation and elongation of linoleate, alpha-linolenate
      and docosahexaenoate in ten fetuses and two nursing infants of chow-fed rhesus
      monkey mothers were studied in vivo using uniformly labeled tracer molecules and
      high precision mass spectrometry. Doses of [U-13C]-18:2n-6, [U-13C]-18:3n-3 or [U
      13C]-22:6n-3 free fatty acids were infused intravenously to the adults, and milk,
      maternal plasma, fetal plasma and tissues, and infant plasma were analyzed for
      enrichment in fatty acids of length C14 to C22. Conversion of tracer fatty acids
      to palmitic, stearic, oleic, and long chain polyunsaturated fatty acids was
      observed in fetal liver, brain, and retina ca. 5 days after dosing, and in milk
      and infant plasma 1 and 7 days after dosing. Animals dosed with [U-13C]-22:6n-3
      accumulated more label in the fetal organs compared to the animals dosed with [U
      13C]-18:3n-3 or [U-13C]-18:2n-6. The greatest fractions of doses were found in
      the fetal brains at levels of 0.21%, 0.24% and 1.7% for the [U-13C]-18:2n-6, [U
      13C]-18:3n-3, and [U-13C]-22:6n-3, dosed mothers, respectively. Label was found
      in saturated and monounsaturated fatty acids in liver, brain and retina (0.05-1.5
      ppm dose/mg lipid) for all doses. These results demonstrate that 1) recycling of
      carbon from 18:2n-6, 18:3n-3, and 22:6n-3 into saturates and monounsaturates is a
      major metabolic pathway in chow-fed primates in the perinatal period; 2) less
      than 2% of the n-3 doses are found in brain fatty acids of developing fetuses
      from chow-fed mothers; and 3) [13C]-22:6n-3 accumulates in retina and brain at an
      order of magnitude higher level when provided as preformed [13C]-22:6 n-3
      compared to [13C]-18:3n-3.

PMID- 9017519
TI  - Serum squalene and noncholesterol sterols before and after delivery in normal and
      cholestatic pregnancy.
AB  - Mechanisms of hyperlipidemia were studied by measurement of serum lipid
      concentrations and the ratios of cholesterol precursors (squalene, delta 8
      cholestenol, desmosterol, and lathosterol), plant sterols (campesterol and
      sitosterol), and cholestanol (a 5 alpha-derivative of cholesterol) to cholesterol
      in nonpregnant women, and normal and cholestatic pregnancies near term, and a few
      days and 6 weeks after delivery. The ratios of the precursors are known to
      reflect cholesterol synthesis, those of plant sterols and cholestanol the
      absorption efficiency and biliary sterol secretion of cholesterol. In normal
      pregnancy, increased serum cholesterol was associated with up to 2-fold increases
      in squalene, desmosterol, and lathosterol proportions, and the values remained
      elevated, especially for desmosterol, during the lactation period. These findings
      suggest that pregnancy and lactation are associated with increased cholesterol
      synthesis. The proportions of plant sterols were slightly lower, but that of
      cholestanol was 2-fold that of the nonpregnant women. In contrast to the latter
      group, the cholestanol proportions were not related to those of plant sterols or
      the campesterol/sitosterol ratio. The values, especially of cholestanol, became
      normal during lactation. In cholestatic pregnancy the changes were basically
      similar, but the serum values of delta 8-cholestenol increased more, and those of
      squalene, desmosterol and lathosterol less markedly, and the mean cholestanol
      proportion was 40% higher and the campesterol/sitosterol ratio 15% lower than in
      the normal pregnancy. Cholestanol was positively related to serum bilirubin and
      bile acids in cholestatic pregnancy, yet only one-third of the cholestatic
      pregnant women exhibited cholestanol values higher than in the healthy pregnant
      women.

PMID- 9017520
TI  - Effects of particle size and number on the plasma clearance of chylomicrons and
      remnants.
AB  - Lymph chylomicrons of different sizes are known to be cleared at different rates,
      but the underlying mechanism for this effect has not been resolved. To
      investigate the differences in clearance rates between small and large particles,
      chylomicron-like lipid emulsions labeled with radioactive triolein and
      cholesteryl oleate were injected into conscious rats. The clearance from plasma
      of small emulsion particles was significantly slower than large when equal lipid
      masses of small and large particles were injected. Similar results were obtained
      in clearance studies with lymph chylomicrons. When equal numbers of either small
      or large emulsion particles were injected into rats, the clearance of the
      triolein label from large particles was significantly slower than small particles
      but no significant difference was found in the clearance of the remnants (traced
      by the cholesteryl oleate label) derived from small and large particles. However,
      when increased numbers of either small or large particles were injected, the
      clearances of emulsion triolein and remnants were significantly decreased. Larger
      particles were found to be lipolyzed significantly less than small. Simultaneous
      injections showed competition for removal of large and small particles,
      suggesting competition for a common, saturable removal process. Our findings
      provide evidence that particle number and size are determinants of the rates of
      plasma clearance of the triglyceride-rich lipoproteins and the results are
      consistent with a saturable process. Our data also show that particle number is
      more important than size and higher numbers of particles markedly affect the
      clearance of triglyceride-rich lipoproteins. However particle uptake by the liver
      is not sensitive to remnant size.

PMID- 9017521
TI  - A novel chemical synthesis of 1-O-hexadecyl-rac-[2-3H]glycero-3
      phosphorylethanolamine and a simple assay for plasmanyl desaturase.
AB  - A simple and efficient method for chemical synthesis of
      lysophosphatidylethanolamine is described. 1-O-hexadecyl diazohydroxyacetone (A.
      K. Hajra, T. V. Saraswathi and A. K. Das. 1983. Chem. Phys. Lipids. 33: 179-193)
      was decomposed by benzyloxycarbonyl (CBZ) derivative of phosphorylethanolamine
      (I) to give 1-O-hexadecyl dihydroxyacetone-3-(N)-CBZ phosphorylethanolamine (II).
      Compound (II) was reduced by NaBH4 and the product (III), after catalytic
      transfer hydrogenolysis produced the final compound, 1-O-hexadecyl-rac-glycero-3
      phosphorylethanolamine (IV). The yield of (IV), starting from 1-O-hexadecyl
      diazohydroxyacetone was 53%. The identities of the compounds were verified by NMR
      and fast atom bombardment mass spectral (FAB-MS) analysis. 1-O-hexadecyl-rac[2
      3H]glycero-3-phosphorylethanolamine prepared by the method above was shown to be
      a good in vitro substrate for plasmanyl delta 1'-desaturase (EC 1.14.99.19).
      Using this radioactive substrate, a simple and rapid solvent partition assay for
      this enzyme was developed with results comparable to those obtained by the two
      dimensional thin-layer chromatographic assay method. The advantage of this rapid
      assay system and the applicability of the chemical synthetic method for other
      phosphoglycerides are discussed.

PMID- 9017522
TI  - Rapid isolation of low density lipoproteins in a concentrated fraction free from
      water-soluble plasma antioxidants.
AB  - A rapid method is described for isolation and concentration of plasma low density
      lipoproteins (LDL) using a Beckman L80 ultracentrifuge equipped with a 70.1 Ti
      fixed angle rotor. The isolation of LDL achieved by a discontinuous gradient
      density step (180 min) was followed by a simultaneous purification and
      concentration step (45 min) using ultrafiltration through a collodium bag under
      nitrogen. This dialysis/concentration step, in contrast to the standard dialysis
      techniques in batch or by filtration through short gel columns, prevents
      oxidation and dilution of the sample. Electrophoresis in agarose and sodium
      dodecylsulfate-polyacrylamide (SDS-PAGE) gels were used to monitor LDL surface
      charge, purity, and contamination with plasma proteins. The artifactual oxidation
      of LDL during isolation and subsequent handling, and thus the ability of LDL
      preparation for oxidation/antioxidation studies, was assessed by the
      determination of endogenous hydroperoxides and thiobarbituric acid reactive
      substances. The dialysis/concentration step by ultrafiltration that allows the
      obtention of a concentrated and purified LDL preparation was validated by the
      absence of ascorbate and urate, as measured by HPLC. This method led to LDL
      preparations free of water-soluble plasma antioxidants that were minimally
      oxidized and suitable for reliable in vitro LDL oxidation and inhibition studies.
      The applicability of this methodology was tested by studying the alpha-tocopherol
      content of LDL in a Portuguese population of university students.

PMID- 9017523
TI  - The role of serotonin in the pathophysiology and treatment of schizophrenia.
AB  - The concept of "balanced serotonergic/dopaminergic antagonists" reflects renewed
      interest in the role of serotonin (5-HT) in schizophrenia. Postmortem brain
      tissue analysis, cerebrospinal fluid studies, and pharmacological challenges
      suggest a deficit in 5-HT function in the cortex of patients with schizophrenia.
      In contrast, however, 5-HT2 antagonism is claimed to have beneficial effects on
      both positive and negative symptoms of the illness. The authors attempt to
      resolve this paradox with a model that takes into account the suggestion of a
      cortical serotonergic hypofunction and a beneficial effect of 5-HT2 antagonism
      via modulation of subcortical dopamine activity. Although involvement of 5-HT in
      schizophrenia is supported by compelling evidence, more research is needed to
      better define its role in pathophysiology and treatment of this illness.

PMID- 9017524
TI  - Posttraumatic stress disorder in patients with traumatic brain injury and amnesia
      for the event?
AB  - Frequency of DSM-III-R posttraumatic stress disorder (PTSD) was studied in 47
      active-duty service members (46 male, 1 female; mean age 27 = 7) with moderate
      traumatic brain injury and neurogenic amnesia for the event. Patients had
      attained "oriented and cooperative" recovery level. When evaluated with a
      modified Present State Examination and other questions at various points from
      study entry to 24-month follow-up, no patients met full criteria for PTSD or met
      criterion B (reexperience); 6 (13%) met both C (avoidance) and D (arousal)
      criteria. Five of these 6 also had organic mood disorder, depressed type, and/or
      organic anxiety disorder. Posttraumatic amnesia following moderate head injury
      may protect against recurring memories and the development of PTSD. Some patients
      with neurogenic amnesia may develop a form of PTSD without the reexperiencing
      symptoms.

PMID- 9017525
TI  - Neuropsychological findings in a sample of Operation Desert Storm veterans.
AB  - In response to ongoing complaints of memory, attention, and problem-solving
      difficulties among veterans of Operation Desert Storm and Shield (ODSS), a sample
      of 44 male veterans of ODSS underwent a comprehensive neuropsychological
      evaluation. Deficits relative to normative data were observed only on finger
      dexterity (Grooved Pegboard, bilaterally) and the Stroop Color and Word Test.
      Those with impaired Pegboard performance had lower performance on other tasks
      requiring psychomotor speed. Those with impaired Stroop had significantly lower
      motor and set-shifting performance. Scores of both impaired groups were higher on
      many clinical and supplemental scales of the MMPI. Despite subjective cognitive
      complaints reported in 39% of the overall sample, veterans with cognitive
      complaints differed from their peers primarily in greater psychological distress
      as depicted on the MMPI. The data are presented as preliminary clinical findings.

PMID- 9017526
TI  - Sustained-release methylphenidate for cognitive impairment in HIV-1-infected drug
      abusers: a pilot study.
AB  - Other investigators have reported clinical improvement from psychostimulant drugs
      in patients with HIV-1-related cognitive impairment. However, no previous
      research has substantiated this claim by using a controlled study design. We
      examined the efficacy of sustained-release methylphenidate (MSR) in a sample of
      substance abusers with HIV-1-related cognitive impairment. Eight HIV-1-infected
      methadone patients with impaired neuropsychological test performance participated
      in an inpatient double-blind placebo-controlled crossover trial of MSR 20-40
      mg/day. On a composite neuropsychological measure, patients improved
      significantly from baseline during MSR but not placebo treatment. Nevertheless,
      MSR performance did not differ significantly from placebo performance. Patients
      appeared to improve as a function of time, regardless of sequence, with somewhat
      more improvement during MSR than placebo treatment.

PMID- 9017527
TI  - Subjective complaints versus actual cognitive deficits in predominantly
      symptomatic HIV-1 seropositive individuals.
AB  - The relationship of self-reported cognitive, motor, and affective complaints to
      actual neuropsychological functioning was explored in a cohort of predominantly
      symptomatic HIV-1 seropositive individuals. Ninety-two symptomatic HIV-1 infected
      subjects were questioned about complaints common in HIV infection and were
      assessed with a comprehensive neuropsychological test battery. No relationship
      was found between subjective complaints and cognitive functioning, yet a
      significant relationship was found between self-reported difficulties and formal
      measures of affect and mood. Failure to show a relationship between self-reported
      cognitive status and actual neuropsychological functioning in this cohort
      suggests that complaints of cognitive decline may be attributable to emotional
      factors.

PMID- 9017528
TI  - Mismatch negativity: an index of subclinical neurological differences in HIV
      patients during rapid perceptual processing.
AB  - Thirteen asymptomatic HIV-infected (HIV+) and 13 healthy control (HIV-) subjects
      were instructed to detect "oddball" target tones from among a sequence of
      nontarget tones delivered rapidly (3 tones/second) in one ear while ignoring a
      similar sequence delivered simultaneously in the opposite ear. Event-related
      potentials (ERPs) to all stimuli were recorded from midline scalp sites. Both
      groups produced ERP correlates, termed the "mismatch negativity" (MMN), to the
      oddball tones during delivery. However, the HIV+ group produced MMNs that
      differed in morphology from those of the HIV-group, suggesting that HIV may alter
      attentional perceptual processing. These results suggest that auditory ERPs
      elicited by rapid, dichotic stimulus presentations may be useful in monitoring
      subclinical effects of HIV-related neuropathology on perceptual processing.

PMID- 9017529
TI  - Blunted left cingulate activation in mood disorder subjects during a response
      interference task (the Stroop).
AB  - Functional neuroimaging studies have found abnormal anterior cingulate activity
      in depressed subjects, and other studies have shown that the cingulate gyrus
      becomes active in healthy subjects during interference tasks. The authors
      hypothesized that subjects with mood disorder might show blunted cingulate
      activation during the standard Stroop interference task or during a modified
      version involving sadness-laden words. In contrast to 11 age- and sex-matched
      healthy control subjects who activated the left cingulate during the standard
      Stroop, 11 mood-disordered subjects activated the right anterior cingulate gyrus
      only slightly and instead showed increased activity in the left dorsolateral
      prefrontal and visual cortex. This study supports theories of blunted limbic and
      paralimbic activation and abnormal cingulate activity in depression and adds to
      the growing knowledge of the functional neuroanatomy of depression.

PMID- 9017530
TI  - Depression, delusions, and hallucinations in Alzheimer's disease: no relationship
      to apolipoprotein E genotype.
AB  - The apolipoprotein E (APOE) locus on chromosome 19 has been shown to modify risk,
      and age at onset, of Alzheimer's disease (AD). The authors hypothesized that the
      phenotypic expression of different psychiatric symptoms in patients with AD would
      be associated with variability in APOE locus. Neuropsychiatric and genetic
      testing of 120 probable AD patients revealed 28% had major depression, 17% had
      minor depression, 30% had delusions, and 14% had hallucinations; 69% were
      carriers of at least one APOE E4 allele (14% homozygous E4/E4, 49% heterozygous
      E3/E4, 6% heterozygous E2/E4, 29% homozygous E3/E3, 2% heterozygous E2/E3).
      Prevalence of the various psychiatric disturbances did not differ significantly
      in AD patients with different APOE genotypes. Apolipoprotein E does not appear to
      modify the risk of developing AD-associated psychiatric symptomatology.

PMID- 9017531
TI  - Correlations between SPECT regional cerebral blood flow and psychometric testing
      in patients with Alzheimer's disease.
AB  - Thirty-nine patients with probable Alzheimer's disease (AD) were studied with
      [99mTc]HMPAO SPECT and a standardized neuropsychological battery testing
      intellect, memory, attention, language, motor and praxis functions, and
      depression. Spearman rank correlations and multivariate regression analyses were
      performed to correlate quantitative regional perfusion deficits to these tests.
      Patients were found to have decreased perfusion of left frontal, parietal, and
      temporal regions relative to right. WAB repetition scores and bilateral temporal
      flow were significantly correlated (P < 0.01). Correlations between visual memory
      and bilateral temporal flow and those between Mini-Mental State/ Geriatric
      Depression Scale scores and bihemispheric flow approached significance. Although
      in this study regional cerebral blood flow was relatively insensitive to
      neuroanatomical abnormalities underlying specific cognitive deficits, it may have
      some specificity for identifying the language disorder in AD.

PMID- 9017532
TI  - Elevated plasma gamma-aminobutyric acid (GABA) levels in individuals with either
      Prader-Willi syndrome or Angelman syndrome.
AB  - Plasma gamma-aminobutyric acid (GABA) levels were measured in 14 subjects with
      Prader-Willi syndrome, 9 subjects with Angelman syndrome, and matched control
      subjects. Mean levels in both patient groups were 2 to 3 times higher than in
      nonretarded moderately obese or retarded nonobese control subjects. Levels in
      each patient group differed significantly from both control groups. Neither the
      two patient groups nor the two control groups differed. GABA levels seemed
      unrelated to genetic status (chromosome 15 deletion or disomy). These preliminary
      findings of elevated plasma GABA levels possibly represent a compensatory
      increase in presynaptic GABA release in response to hyposensitivity of a subset
      of GABA receptors and could produce increased postsynaptic activation of other
      normal GABA receptor subtypes, resulting in complex alterations of GABAergic
      function throughout the brain.

PMID- 9017533
TI  - Cognition, negative symptoms, and diagnosis: a comparison of schizophrenic,
      bipolar, and control samples.
AB  - Forty-six schizophrenic, 22 bipolar, and 26 normal control subjects were
      administered negative and positive symptoms scales and tests of cognitive
      function. Test performance was related to diagnosis and to positive and negative
      symptom ratings within the schizophrenic group. Bipolar patients were
      significantly superior in cognitive status when compared with all schizophrenic
      patients, but less so when compared only with those who did not have key negative
      symptoms (affective nonresponsivity and poverty of speech). The schizophrenic
      patients with negative symptoms displayed severe impairment, performing
      significantly worse than the control, bipolar, and other schizophrenic subjects.
      Negative symptoms thus are significantly implicated in the cognitive inferiority
      of schizophrenic to bipolar patients. Although the data suggest bipolar patients
      may also have cognitive deficiencies, these findings are inconclusive and require
      cross-validation.

PMID- 9017534
TI  - Preattentive and attentive eye movements during visual scanning of a cocaine cue:
      correlation with intensity of cocaine cravings.
AB  - The visual scanning of 19 recently abstinent crack cocaine-dependent men was
      assessed while they viewed a picture of a cocaine cue and a picture of a neutral
      cue. Cocaine craving scores were inversely correlated with the number of
      preattentive fixations and saccades and were positively correlated with the
      number of attentive fixations.

PMID- 9017535
TI  - Corticobasal degeneration: neuropsychological and clinical correlates.
AB  - A comprehensive neuropsychological test battery was administered to 3 patients
      who met the clinical criteria of corticobasal degeneration (CBD). The pattern of
      neuropsychological deficits in CBD appears to be a distinctive mixture of
      posterior cortical dysfunction and frontal-subcortical system impairment.

PMID- 9017536
TI  - Application of ictal brain SPECT for differentiating epileptic from nonepileptic
      seizures.
AB  - The authors report 2 clinical cases that illustrate the difficulties with video
      monitored EEG and the advantages of brain SPECT in differential diagnosis of true
      epileptic seizures and nonepileptic seizures. Injection of [99mTc]HMPAO at the
      time of the ictal event provides a means to obtain a SPECT image postictally for
      comparison with interictal examinations so that an epileptic or nonepileptic
      focus may be localized.

PMID- 9017537
TI  - Forensic issues in the neuropsychiatric evaluation of the patient with mild
      traumatic brain injury.

PMID- 9017538
TI  - Psychiatric effects of felbamate.

PMID- 9017539
TI  - Second stage of labor.

PMID- 9017542
TI  - Prevention of pregnancy and STDs.

PMID- 9017541
TI  - Apgar score.

PMID- 9017543
TI  - Dyspareunia: three case reports.
AB  - Dyspareunia, a symptom rather than a diagnosis, is defined as pain experienced by
      a woman during intercourse. This article discusses how to elicit an accurate
      sexual history and lists 12 common causes of dyspareunia. Three case reports from
      the authors' practices will be used to describe the diagnosis and treatment of
      women with vulvar vestibulitis, hymenal strands, and vaginismus.

PMID- 9017544
TI  - The nurse's role in the identification of risks and treatment of shoulder
      dystocia.
AB  - Shoulder dystocia is a clinical emergency that requires immediate recognition and
      prompt treatment to minimize maternal and neonatal sequelae. The nurse's role is
      to recognize and report associated risk factors for shoulder dystocia, respond
      with appropriate assistance, and monitor the woman and her newborn after
      delivery. The nurse's calm demeanor, knowledge of treatment modalities, and
      prepared response are valuable assets in this clinical dilemma.

PMID- 9017545
TI  - Responses of pregnant women to potential preterm labor symptoms.
AB  - OBJECTIVE: To examine the knowledge that healthy pregnant women have of
      appropriate actions to take in response to hypothetical symptoms of preterm
      labor. DESIGN: This was a descriptive, correlational study using a convenience
      sample. SETTING: Subjects were recruited from the private practices of
      obstetricians and nurse-midwives. PARTICIPANTS: Three hundred twenty pregnant
      women who were between 20 and 32 weeks gestation were asked to complete a 17-item
      demographic information sheet and an 18-item Health Pregnancy Questionnaire while
      waiting for prenatal visits. Questionnaires from 269 women were appropriate for
      analysis. RESULTS: Most respondents could select appropriate action responses to
      items that identified obvious symptoms of being in preterm labor. In response to
      three questions that posed hypothetical preterm labor symptoms that were more
      subtle or were similar to normally occurring discomforts of pregnancy, between
      26% and 35% of the women selected a choice that would have delayed entry into
      care. With a 95% confidence interval, significant positive relationships were
      found between selecting best responses and having experienced a previous preterm
      labor and maternal age. CONCLUSION: This study supports the need for all pregnant
      women to receive information on identification of preterm labor symptoms and
      appropriate actions to take with regard to these symptoms.

PMID- 9017546
TI  - Parents' experience surrounding the death of a newborn whose birth is at the
      margin of viability.
AB  - OBJECTIVE: To describe the experience of parents surrounding the death of a
      newborn weighing less than 500 g at birth. DESIGN: Descriptive, using an eidetic
      phenomenologic approach. SETTING: Interviews were conducted in the parents' homes
      or by telephone between 4 and 15 weeks after the loss. PARTICIPANTS: Eight
      parents (five mothers and three of their husbands) who had experienced the death
      of a newborn weighing less than 500 g at birth. MAIN OUTCOME MEASURES: The lived
      parental experience of the death of a newborn consists of a number of parental
      processes, responses, and activities that occur over time. RESULTS: Five themes
      were generated from the data: (a) realization that the loss is occurring; (b)
      initial response to the loss; (c) decision making at the time of the loss; (d)
      components of supportive relationships with others; and (e) the adjustment at
      home. CONCLUSIONS: The findings demonstrate the unique experience of having a
      newborn who is born at the margin of viability and support the need for
      individualized, caring-based interventions for parents.

PMID- 9017547
TI  - Does application of tea bags to sore nipples while breastfeeding provide
      effective relief?
AB  - OBJECTIVE: To evaluate effectiveness of water versus tea bag compresses in
      treatment of sore nipples during breastfeeding. DESIGN: Prospective, randomized
      trial. SETTING: Mother-infant care wards in a tertiary care teaching hospital.
      PARTICIPANTS: Sixty-five primiparae with sore nipples who were breastfeeding
      after a vaginal delivery at 37 or more weeks gestation, who were 36 hours or less
      postpartum, and had combined mother-infant care. INTERVENTIONS: Participants were
      assigned randomly to one of six treatment groups with one of three regimens (tea
      bag compress, water compress, or no compress) randomly assigned to right or left
      sides. Participants applied the treatments at least four times a day, from Days 1
      to 5 postpartum. MAIN OUTCOME MEASURE: Reduction of nipple pain. RESULTS: Tea bag
      and water compresses were more effective than no treatment, with no statistically
      significant difference between the two types of compresses. CONCLUSION: Warm
      water or tea bag compresses are an inexpensive, equally effective treatment for
      sore nipples during the early postpartum period.

PMID- 9017548
TI  - Parental evaluation of a tour of the neonatal intensive care unit during a high
      risk pregnancy.
AB  - OBJECTIVE: To describe parents' reaction to a prenatal tour of the neonatal
      intensive care unit (NICU) during a high-risk pregnancy and identify advice they
      have for other parents and health care professionals who participate in a such a
      tour. DESIGN: Naturalistic inquiry, a qualitative approach. SETTING:
      Semistructured interviews were conducted in the hospital or parents' home.
      PARTICIPANTS: Thirteen expectant parents who had toured a NICU during a high-risk
      pregnancy. MAIN OUTCOME MEASURES: Three categories of information were described
      by the parents: (a) a description of the tour; (b) benefits of the tour; and (c)
      an evaluation of the way that the tour was arranged and conducted, including
      advice to health care professionals and other parents. RESULTS: All parents
      recommended that parents diagnosed with a high-risk pregnancy be offered a
      prenatal tour of the NICU. The tour benefited parents and (a) decreased fears,
      (b) inspired hope for the infant's prognosis, (c) provided reassurance about the
      care in the NICU, and (d) prepared parents for their infant's hospitalization in
      the NICU. CONCLUSIONS: Parents experiencing a high-risk pregnancy benefit from a
      tour of the NICU. The tour familiarized parents with the NICU and the type of
      care that their newborn would require. However, during the tour, more attention
      should be given to the parental role in the NICU.

PMID- 9017549
TI  - Aortic stenosis in pregnancy: a case report.
AB  - This case report describes a pregnant patient with severe aortic stenosis. A
      multidisciplinary plan of care was developed for the antepartum, intrapartum,
      postpartum, and, ultimately, postoperative clinical course. Salient points
      reviewed include normal cardiovascular anatomy and physiology, hemodynamic and
      physiologic changes of pregnancy, bicuspid aortic valvular stenosis, and the
      patient's clinical data profile. Numerous psychosocial stresses and the need for
      specialized nursing added to the complexity of caring for this patient.

PMID- 9017550
TI  - The Breast Cancer Prevention Trial: evaluating tamoxifen's efficacy in preventing
      breast cancer.
AB  - OBJECTIVE: To review the literature on tamoxifen and breast cancer, focusing on
      the Breast Cancer Prevention Trial (BCPT). DATA SOURCES: Computerized searches on
      MEDLINE and CINAHL. STUDY SELECTION: Articles from indexed journals in the
      English language related to the topics in this review and published after 1983
      (except for earlier classic pieces) were evaluated. DATA EXTRACTION: Data were
      extracted and information was organized under the following headings: magnitude
      of the problem of breast cancer, definition of chemoprevention, tamoxifen's mode
      of action, risks and benefits, use as an adjuvant and in chemoprevention, the
      BCPT, study protocol, pros and cons, and nursing implications. DATA SYNTHESIS:
      The BCPT is a study testing tamoxifen's ability to prevent the development of
      breast cancer in healthy women at increased risk for developing the disease.
      About 16,000 women who are age 35 years or older are being randomized to receive
      oral tamoxifen (20 mg/day) or placebo for an initial period of 5 years.
      CONCLUSIONS: The BCPT will contribute to our knowledge about tamoxifen's ability
      to prevent breast cancer in women at increased risk. Nurses have a role to play
      in implementing this strategy to find a means for preventing breast cancer.

PMID- 9017551
TI  - On the horizon: new options for contraception.
AB  - Future contraceptives include refinements of existing contraceptives and totally
      new methods. New formulations of oral contraceptives, subdermal hormonal
      implants, injectable hormones, vaginal spermicides, and intrauterine devices
      (IUDs) are being tested around the world. New methods that are not yet available
      include the use of vaginal preparations containing sperm-immobilizing agents,
      gonadotrophin releasing hormone agonists and antagonists, vaccines against ova
      and sperm, and endogenous hormones. Male contraceptive methods use hormones to
      suppress testosterone and vaccines to immobilize sperm. The availability of all
      future contraceptives is dependent on ample funds for research, development, and
      testing, and such funds are in jeopardy.

PMID- 9017552
TI  - Advanced practice nursing: back to the future.
AB  - Advanced practice nursing has evolved during the last 25 years in important ways
      to become a central component of the new health care system. The quality of care
      and cost effectiveness of practice for various advanced practice roles has been
      well documented. New roles are being created as the demand-driven health care
      system presents opportunities for innovative practice models. It is incumbent on
      nursing to prove its ability to assume full accountability and responsibility so
      that full freedom to practice may be achieved.

PMID- 9017553
TI  - Family health care delivery for the 21st century.
AB  - Families are where individuals learn lifelong health attitudes and health
      behaviors. Factors are discussed that will shape the delivery of family health
      care into the 21st century. Data on issues and trends from the past decade
      concerning demographic, economic, epidemiologic, and primary health care generate
      conclusions about family health care needs. Implications for family health care
      delivery, health policy, and research are discussed.

PMID- 9017554
TI  - Coexisting mental illness and alcohol and other drug dependencies in pregnant and
      parenting women.

PMID- 9017555
TI  - Background and overview of mental health and substance abuse treatment systems:
      meeting the needs of women who are pregnant or parenting.
AB  - Women with a psychiatric disorder who also abuse alcohol or other drugs have
      historically encountered barriers to integrated treatment for both disorders.
      Substance abuse treatment services and mental illness treatment services are
      usually organized independently of each other and few are designed to meet the
      needs of pregnant and parenting women. This chapter reviews the developmental
      histories of treatment systems for psychiatric and substance abuse disorders; the
      structural barriers that impede the delivery of services to individuals with co
      occurring psychiatric and substance abuse disorders; the prevalence of dual
      disorders; issues related to diagnosis and assessment, types of diagnoses and
      addictions; treatment issues specific to women who are pregnant or parenting;
      models of service delivery; and initiatives directed at changing treatment
      systems.

PMID- 9017556
TI  - Psychiatric problems among alcohol and other drug dependent women.
AB  - This article focuses on assessment and treatment of psychiatric disorders within
      the alcohol and drug treatment and recovery system. Inasmuch as women are
      represented in all categories of psychiatric disorders, the article begins with a
      discussion of basic principles of assessment and treatment, examines some of the
      barriers to good practice, and offers recommendations for reducing them. The
      article then reviews in greater detail the psychiatric disorders most frequently
      found in women seeking help in alcohol and drug treatment settings, adding
      considerations relevant to those particular disorders. A brief review of key
      elements to facilitate planning, ongoing monitoring, and evaluation by treatment
      and recovery service providers is provided.

PMID- 9017557
TI  - The effects of dual diagnosis on pregnancy and parenting.
AB  - The desire to give birth and nurture can be significant for women with mental
      illness and substance-abuse disorders, despite the many internal and external
      barriers to the effective achievement of these desires. This article provides
      information on the effect of coexisting mental illness and alcohol or other drug
      dependency on pregnancy from a medical, obstetric, psychiatric, and psychologic
      perspective. The article also explores the effect on parenting and highlights the
      need to assess for parental competency in this population. Treatment planning,
      including the use of psychotropic medication and the need for collaboration
      between providers is discussed.

PMID- 9017558
TI  - PROTOTYPES: an urban model program of treatment and recovery services for dually
      diagnosed perinatal program participants.
AB  - PROTOTYPES, a women's treatment program located in Los Angeles, is described in
      terms of its services for pregnant and parenting women with coexisting substance
      abuse and mental health disorders. The philosophy of treatment, goals and
      objectives, treatment planning process, and treatment content are discussed.
      Management of the milieu, relational model considerations and staff self-care
      issues are presented in addition to future directions in treatment and research
      on women with coexisting disorders.

PMID- 9017559
TI  - A rural collaborative model of treatment and recovery services for pregnant and
      parenting women with dual disorders.
AB  - In this article, the organization of services for the treatment of women with
      dual disorders in Fresno County, California is discussed. The collaboration
      between the Mental Health Department, with its system of services for persons
      with chronic mental illness, and the Substance Abuse Division of the County
      Mental Health Department, which provides perinatal treatment and recovery
      services, is described. The philosophy of treatment and a description of the
      services provided in Fresno County are addressed in addition to future directions
      in the treatment of dual diagnosis disorders.

PMID- 9017560
TI  - Substance abuse and past incest contact. A national perspective.
AB  - Seven hundred thirty-two volunteer participants enrolled in 35 substance abuse
      treatment facilities across the United States were surveyed to examine the
      prevalence and nature of incest contacts among adults receiving substance abuse
      treatment. Results indicated that approximately 36% of the sample reported
      histories of incest: by gender, 29% of the male and 55% of the female
      participants reported incest histories. Data are presented regarding the age
      during incest contact, frequency of contacts and involvement of force, alcohol,
      and drugs. In addition, comparisons between incest and nonincest groups of
      participants are presented. Implications for substance abuse treatment facilities
      and staff are presented.

PMID- 9017561
TI  - The impact of outpatient drug services on abstinence among pregnant and parenting
      women.
AB  - Although there is an increasing number of outpatient drug programs, there remains
      little consensus on which service components are most effective for pregnant and
      parenting women seeking treatment. In this investigation, we studied 48 women who
      remained in treatment for 5 consecutive months to: (1) examine differences
      between clients who maintained 30 to 90 days of abstinence and those who did not
      and (2) test the association between services and abstinence. Although we found
      no demographic differences between abstinent and nonabstinent women, we did find
      that significantly more abstinent women received family therapy services compared
      to nonabstinent women as they remained in treatment. Furthermore, we found that
      clients who were abstinent tended to receive more services overall than those who
      were not. Providers need to consider their population when deciding on which
      service components will be included: and family therapy is one service component
      that should be available to pregnant and parenting women.

PMID- 9017562
TI  - Feasibility of smoking cessation counseling by phone with alcohol treatment
      center graduates.
AB  - Several studies have tested the effectiveness of telephone counseling as a
      smoking cessation intervention, but few have addressed its application with the
      special population of smokers who are also problem drinkers or recovering
      alcoholics. Two hundred and eighty-eight male and female subjects were recruited
      from six residential alcohol treatment programs in Nebraska, Iowa, and Kansas to
      receive three postreatment telephone calls based on the stages of change model.
      Most subjects (71%) participated in at least one telephone counseling session,
      but only 38% participated in all three. Those who completed of session were
      significantly (p < .01) more likely to have advanced one stage of change in their
      readiness to quit smoking and to report having quit smoking for at least 24 hours
      since leaving treatment (p < .01). Stage-based telephone counseling appears to be
      a feasible approach to addressing smoking cessation among recovering alcoholics,
      with a modest positive effect on subsequent tobacco use.

PMID- 9017563
TI  - The trajectory of client progress. A longitudinal pilot study.
AB  - Successful nonchemical drug treatment is a transformative experience: client
      change is the goal of treatment. Two domains in which programs intend to
      facilitate change are emotional well-being and the therapeutic relationship.
      Little previous research has addressed the question of what changes clients in
      drug treatment actually undergo while in treatment. This article presents results
      from a pilot longitudinal study of clients in two short-term drug treatment
      programs in Houston, TX. Results showed measurable increases in self-esteem and
      connection to counselor and decreases in anxiety and depression over the course
      of treatment for clients who completed treatment. Program graduates and early
      withdrawals showed distinctly different patterns of progress as measured by
      emotional and relationship scales.

PMID- 9017564
TI  - An intensive program for collegiate substance abusers. Progress six months after
      treatment entry.
AB  - The New Jersey Collegiate Substance Abuse Program (NJCSAP) provided intensive
      substances abuse treatment to college students requiring treatment for severe
      substance use disorders. This study reports the progress of students who received
      6 months of treatment of NJCSAP and participated in a research evaluation of the
      program. Overall, 74.5% of participants who completed the follow-up were
      abstinent at the 6-month assessment. Including participants who did not complete
      the follow-up as user yielded a 52.6% rate of abstinence. Students who completed
      the follow-up experienced decreases in the number of current psychiatric
      diagnoses met, depressive symptomatology, alcohol and drug problem severity, and
      family and psychiatric problem severity over the 6 month period. Most students
      rated the program components as very or moderately helpful and most were
      attending AA at the 6-month assessment. Result are compared to findings from
      other programs for adolescents and young adults.

PMID- 9017565
TI  - Trauma and short-term outcome for women in detoxification.
AB  - The present study documents short-term outcomes for women receiving inpatient
      detoxification. We also aimed to determine the association between trauma history
      and these outcomes. One hundred and one randomly selected inner-city women
      completed a structured questionnaire covering demographic, treatment, and trauma
      history. All received follow-ups to trace postdischarge disposition 59.4% (n =
      60) were classified with positive short-term outcome. Statistically significant
      relationships were found between positive outcome and both member of previous
      detox hospitalizations (R = .20 p < .05) and attendance at outpatient programs (R
      = 35, p < .05). No significant relationships were demonstrated between outcome
      and histories of violence, use of drugs, or any demographic characteristics.
      Identifying histories of trauma did not interfere with treatment completion or
      further treatment seeking. Our results suggest that for women with heavy drug and
      alcohol problems, the capacity to accept and utilize help may be developed over
      repeated treatment exposures rather than related to intrinsic character trails.

PMID- 9017566
TI  - Ethnic matching of caseworker and patient in methadone maintenance.
AB  - The relation of ethnic matching of caseworker and patient to treatment outcomes
      was evaluated in a cohort of 610 opioid users admitted to methadone maintenance.
      At admission, the subjects were assigned to caseworkers in rotation. Thirty-seven
      percent of the Anglo subjects, 11% of the African-American subjects, and 60% of
      the Hispanic subjects were matched with caseworkers of their own ethnic group. In
      all ethnic groups, the matched and nonmatched subgroups did not differ
      significantly on 11 pretreatment characteristics. The subgroups also did not
      differ significantly on 3 treatment variables, with the exception of methadone
      dose in the Anglo group. The Anglo-matched subgroup had a slightly higher mean
      dose (61 mg) than did the not matched subgroup (52 mg). In all ethnic groups, the
      matched and nonmatched subgroups did not differ significantly on 12 outcome
      variables. No relation was found between ethnic matching and treatment outcomes.

PMID- 9017567
TI  - Methadone maintenance and other factors associated with intraindividual temporal
      trends in injection-drug use.
AB  - The objective of this study was to determine what sociodemographic, lifestyle, or
      drug-related characteristics predict temporal changes in self reported drug
      injection frequencies among HIV-seronegative injection-drug users (IDUs) who were
      being given HIV testing and risk reduction counseling. The 277 subjects were
      given 4-11 quarterly interviews including detailed history of drug use and other
      HIV risk factors, HIV risk reduction counseling, and venipuncture for HIV
      antibody testing. A regression slope of change over time in drug injection
      frequency was calculated for each subject, and categories were created of
      decreasing temporal slope, increasing slope, relapse (decrease initially, then
      increase), or no substantial change. Only 44% of subjects decreased their drug
      injection frequencies despite repetitive HIV testing and counseling. In
      multivariate logistic analyses, decreasing temporal trends were associated with
      consistent enrollment in methadone maintenance (p < .1), whereas increasing
      trends conversely were associated with inconsistent enrollment (p < .01) and also
      with an absence of crack use (p < .01). Relapses were significantly associated
      with needle sharing with multiple partners and a low frequency of smoking. The
      data suggest that methadone maintenance facilitates a positive response to HIV
      risk reduction counseling. However, the fact that only a minority of subjects
      displayed a decreasing temporal trend in drug injection frequencies emphasizes
      the need for improved therapeutic and counseling techniques.

PMID- 9017568
TI  - What happens when a demonstration project ends. Consequences for a clinic and its
      clients.
AB  - The Los Angeles Enhanced Methadone Maintenance Project was a 5-year research
      demonstration project funded by the National Institute on Drug Abuse with the
      goal of reducing high-risk behavior for human immunodeficiency virus (HIV) among
      heroin users. A clinic was established for the purposes of the study and 500
      clients with high-risk profiles were recruited into treatment. Follow-up
      assessments demonstrated that clients had reduced their drug use, criminal
      behavior, and HIV-risk behaviors after entering treatment. At the end of the
      project clients were given the option of continuing treatment at the clinic on a
      fee-for-service basis, transferring to another treatment provider, or undergoing
      detoxification. Clients who were eligible for Medicaid were likely to continue
      receiving methadone treatment, but those without Medicaid funding were not. The
      implications of terminating treatment among a high-risk population recruited into
      a research demonstration project are discussed.

PMID- 9017569
TI  - Treatment utilization and personality organization among drug abusers in Sweden.
AB  - Treatment utilization and personality organization in a case-finding sample of
      1824 drug abusers in the greater Stockholm area were assessed by using a
      standardized questionnaire, with the client's contact persons as informants.
      Level of personality organization was strongly associated, negatively with the
      number of concurrent treatment contacts, problems of coordination between
      concurrent treatment agents, and was positively correlated with agreement between
      treatment agents in the assignment of principal treatment responsibility and
      their opinions about the appropriateness of this assignment. Psychiatric ICD-9
      diagnosis was not associated with any of these variables.

PMID- 9017570
TI  - Therapeutic community retention among Alaska Natives. Akeela house.
AB  - The purpose of the study was to determine whether a change in the treatment
      program at Akeela House Incorporated a therapeutic community in Anchorage.
      Alaska, significantly increased the time in treatment for Alaska Native
      residents. The change in treatment involved implementation of culturally
      sensitive approaches that incorporated and reinforced Native lifestyles. Data
      were obtained from the Alaska Management Information System on all treatment
      admissions from January 1988 to January 1995. Prior to implementation, Alaska
      native residents had significantly shorter times in treatment that Black or White
      residents. After implementation of the change in the treatment program, Alaska
      Native residents' times in treatment were no longer significantly different from
      those of Black or White residents and all three ethnic groups had significantly
      longer times in treatment than before the intervention.

PMID- 9017571
TI  - The development of a partial hospitalization program for mentally ill chemically
      abusing [MICA] patients.

PMID- 9017580
TI  - Recent advances in lung cancer surgery in Europe.

PMID- 9017581
TI  - Interleukin-2 receptors in pulmonary adenocarcinoma tissue.
AB  - We previously reported that the serum soluble interleukin-2 receptor (sIL-2R)
      level increased with the advance of disease stage in non-small cell lung cancer.
      The present study was thus conducted to investigate the origin of serum sIL-2R in
      patients with pulmonary adenocarcinoma. Fresh tumor cell suspensions were
      prepared from surgically resected specimens of pulmonary adenocarcinoma. They
      were adjusted to a cell density of 5 x 10(5)/ml and then cultured for 24 h at 37
      degrees C. The culture supernatants were collected and assayed to determine the
      sIL-2R levels using an enzyme immunoassay. The resultant cells were thereafter
      cytocentrifuged onto glass slides and immunochemically stained with anti-human IL
      2R alpha (CD25) monoclonal antibody. In three of six cases examined, a
      substantial level of sIL-2R was identified in the culture supernatants. In four
      cases, including those three cases with the presence of sIL-2R in the culture
      supernatants, various proportions of tumor cells were positively stained with the
      anti-IL-2R alpha antibody. Further examinations revealed that tumor cells
      expressed IL-2R alpha (CD25) in seven of 16 cases with pulmonary adenocarcinoma.
      These results thus suggested that the tumor cells did express IL-2R alpha and
      release sIL-2R in some cases with pulmonary adenocarcinoma.

PMID- 9017582
TI  - Prognostic factors for response to chemotherapy containing platinum derivatives
      in patients with unresectable non-small cell lung cancer. (NSCLC).
AB  - PURPOSE: To identify pretreatment variables predicting response to platinum
      derivatives containing chemotherapy in patients with unresectable non-small cell
      lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients included in one of
      the 7 consecutive clinical trials conducted by the European Lung Cancer Working
      Party between December 1980 and August 1991. All patients received a cisplatin or
      carboplatin containing chemotherapy. We analyzed 22 potential prognostic factors
      including sex, age, histology, performance status, weight loss, type of lesions,
      extent of disease, main metastatic sites and several biological parameters,
      namely white blood cell count (WBC), neutrophil count, platelet count,
      hemoglobinemia, creatininemia, serum alkaline phosphatases and LDH. RESULTS: On
      1052 eligible patients. 107 were not assessable for response. The objective
      response rate was 26% (95% C.I.: 23, 29%). Univariate analysis identified as
      statistically significantly associated with a higher objective antitumoral
      response rate the following characteristics: a normal platelet count, the absence
      of skin metastasis, the absence of adrenal metastasis, a higher creatininemia, a
      normal hemoglobinemia, an older age and a normal WBC count. On a restricted set
      of variables including data from 777 patients, a multivariate logistic regression
      model disclosed age and platelet count as significantly and independently related
      to response rate. CONCLUSION: Clinical and demographic characteristics of
      patients with unresectable NSCLC, as well as routine laboratory parameters, could
      not accurately predict response to chemotherapy in a population of patients
      selected for a clinical trial. Future studies on this subject should include more
      sophisticated variables as new biomolecular makers.

PMID- 9017583
TI  - Prognostic factors in resected non-small cell lung cancer: an immunohistochemical
      study of 39 cases.
AB  - Non-small cell lung carcinoma (NSCLC) is a histologically heterogeneous
      collection of tumours with variable clinical behaviour. Performance status,
      tumour stage and histological type have important prognostic implications, but
      the clinical outcome in an individual patient remains unpredictable. In search of
      other prognostic factors we studied the expression of several immunohistochemical
      markers in NSCLC, resected with curative intent. Tumour samples of 19 patients
      with a postoperative disease-free survival of at least 5 years and those of 20
      patients who died of tumour recurrence within 2 years after resection were
      selected for this study. The populations were matched for age, sex and tumour
      stage. We investigated the expression of markers for neuroendocrine
      differentiation, cell adhesion and cell cycle regulation in both populations.
      None of the investigated immunohistochemical markers distinguished between long-
      and short-term survivors of resected NSCLC. In stage 1 tumours expression of
      embryonal NCAM was observed more often in the short survival group (P = 0.026)
      and in stage 3a EGF-r expression was associated with the long survival group (P =
      0.047). However, these findings remained to be confirmed. Expression of Rb, NCAM
      and embryonal NCAM was not detected in adenocarcinomas, whereas T-Ag and
      chromogranin A immunoreactivity was absent from squamous cell carcinomas.

PMID- 9017584
TI  - Plasma transforming growth factor-beta 1 reflects disease status in patients with
      lung cancer after radiotherapy: a possible tumor marker.
AB  - PURPOSE: To determine the frequency with which elevated plasma transforming
      growth factor-beta 1 (TGF beta 1) concentrations occur in lung cancer patients,
      to determine the kinetics of TGF beta 1 expression during and after radiotherapy
      and to correlate plasma TGF beta 1 levels with disease status after treatment.
      MATERIALS AND METHODS: Plasma samples were obtained before, during and after
      radiotherapy in 54 patients with lung cancer and 20 normal controls. Plasma TGF
      beta 1 levels were measured using an enzyme-linked immunosorbent assay. RESULTS:
      Baseline TGF beta 1 levels in lung cancer patients and normal controls were 13.0
      +/- 2.5 and 4.4 +/- 0.3 ng/ml, respectively. Elevated TGF beta 1 were found in
      50% (27/54) of lung cancer patients. During radiation therapy plasma TGF beta 1
      levels declined, however, by the completion of treatment the mean TGF beta 1
      level had not normalized in patients with lung cancer. The TGF beta 1 level at
      last follow-up correlated with disease status in those patients with an increased
      pretreatment plasma level. Three of four patients with no evidence of cancer had
      normal follow-up TGF beta 1 levels, compared to 2/16 patients with residual or
      recurrent tumor (P = 0.02). CONCLUSIONS: Elevated plasma TGF beta 1 levels occur
      frequently in patients with lung cancer. In those patients with an elevated
      plasma TGF beta 1 level at diagnosis, monitoring this level may be useful in
      detecting both disease persistence and recurrence after therapy.

PMID- 9017586
TI  - Ifosfamide combined with toremifene in the treatment of non-small cell lung
      cancer.
AB  - The efficacy and safety of toremifene-ifosfamide as a first-line chemotherapy in
      non-small cell lung cancer were assessed. Sixteen patients were treated with oral
      toremifene (420 mg on days 1-4 and 240 mg on day 5) followed by ifosfamide
      infusion 5 g/m2 on day 5 every 3 weeks 1-6 times. Toremifene at the doses used
      did not enhance the effect or toxicity of ifosfamide in previously untreated non
      small cell lung cancer patients.

PMID- 9017585
TI  - Phase II study of alternating doses of vinorelbine in combination with cisplatin
      for non-small cell lung cancer (NSCLC): a disappointing experience.
AB  - In both Phase III trials of vinorelbine-cisplatin (VP) versus single-agent
      vinorelbine, the received vinorelbine dose intensities were 18.8 and 21.1 mg/m2
      per week in the VP arms. Vinorelbine was administered at the weekly dose of 30
      mg/m2. A new structure of the vinorelbine-cisplatin regimen delivering
      alternating doses of vinorelbine (35 mg/m2 on weeks 1, 3, 5 and 17.5 mg/m2 on
      weeks 2 and 4) was reported to increase the vinorelbine dose intensity in
      patients with non-small cell lung cancer (NSCLC). To further analyze the ability
      of such an alternating vinorelbine schedule to enhance vinorelbine delivery, a
      Phase II study of VP was conducted in NSCLC patients using the previously
      published alternating doses of vinorelbine for 6 cycles. Cisplatin was
      administered on weeks 1, 5 and every 6 weeks thereafter, at a dose of 75 mg/m2 in
      the first 14 patients and at a dose of 100 mg/m2 in the 18 remaining patients.
      The intended vinorelbine dose intensity was 26.25 mg/m2 per week. The median
      delivered dose intensities of vinorelbine calculated during the first 8-week
      period were: all patients, 17.9 mg/m2 per week; patients treated with cisplatin
      75 mg/m2, 18.1 mg/m2 per week; patients receiving cisplatin 100 mg/m2, 17.9 mg/m2
      per week; naive patients 18.2 mg/m2 per week and previously treated patients.
      13.2 mg/m2 per week. Reductions and delays in the vinorelbine treatment mostly
      occurred on weeks 3 and 7, which are times of high-dose treatments (35 mg/m2)
      according to the protocol. The partial response rate was 34% (95% C.I. = 26-42%).
      Median survival was 21 weeks. The main toxicities were febrile neutropenia (nine
      patients, including two septic deaths) and constipation Grades 3 and 4 (five
      patients). CONCLUSION: The use of alternating doses of vinorelbine within the VP
      regimen did not lead to higher vinorelbine delivered dose intensities than those
      reported with a standard weekly 30 mg/m2 administration.

PMID- 9017587
TI  - Primary hemangiosarcoma of the mediastinum.
AB  - A case of a 44-year-old female who had an intrathoracic mass that was found to be
      a hemangiosarcoma of the anterior mediastinum is reported. Radical surgical
      incision through a right anterior thoracotomy was performed, followed by post
      operative radiotherapy. Since this is a rare tumor at this location, the clinical
      and radiological findings, the histopathological appearances and its therapeutic
      management are discussed. Radiologists, surgeons and oncologists should in the
      differential diagnosis of a mediastinal mass include that of a tumor of vascular
      origin, even if it is rare. Radical excision followed by post-operative
      radiotherapy, especially in cases where the tumor has been partially excised, is
      the treatment of choice.

PMID- 9017588
TI  - Small cell carcinoma of the pleura. A case report.
AB  - Small cell carcinoma of the lung (SCLC) represents about 25% of all lung cancers.
      Extrapulmonary small cell carcinoma is a very uncommon feature, mostly described
      in the oesophagus. We report here a case of small cell carcinoma of the pleura
      with histopathological findings, clinical course and response to therapy typical
      of SCLC.

PMID- 9017589
TI  - Endobronchial extramedullary plasmacytoma. Report of one case.
AB  - A patient underwent a subtotal resection of the tracheobronchial carina for an
      obstructing endobronchial lesion. Preoperative biopsies of the lesion were not
      diagnostic. After resection, the histological examination of the specimen removed
      demonstrated an extramedullary plasmacytoma infiltrating the bronchial wall.
      Immunohistochemical studies showed monoclonality for kappa light chains. The
      postoperative course was uneventful and the screening for multiple myeloma was
      negative. No adjuvant treatment was given and the patient is currently alive and
      free of disease 63 months after the resection. Primary endobronchial plasmacytoma
      is a very rare disease: it is unclear which is the best treatment for
      endobronchial plasmacytoma. However, complete surgical resection has allowed a
      long-term survival, free of disease.

PMID- 9017590
TI  - Studies concerning high dose ifosfamide to patients suffering from malignant
      mesothelioma.

PMID- 9017591
TI  - Three-dimensional analysis and ultrastructural design of mitotic spindles from
      the cdc20 mutant of Saccharomyces cerevisiae.
AB  - The three-dimensional organization of mitotic microtubules in a mutant strain of
      Saccharomyces cerevisiae has been studied by computer-assisted serial
      reconstruction. At the nonpermissive temperature, cdc20 cells arrested with a
      spindle length of approximately 2.5 microns. These spindles contained a mean of
      81 microtubules (range, 56-100) compared with 23 in wild-type spindles of
      comparable length. This increase in spindle microtubule number resulted in a
      total polymer length up to four times that of wild-type spindles. The spindle
      pole bodies in the cdc20 cells were approximately 2.3 times the size of wild
      type, thereby accommodating the abnormally large number of spindle microtubules.
      The cdc20 spindles contained a large number of interpolar microtubules organized
      in a "core bundle." A neighbor density analysis of this bundle at the spindle
      midzone showed a preferred spacing of approximately 35 nm center-to-center
      between microtubules of opposite polarity. Although this is evidence of specific
      interaction between antiparallel microtubules, mutant spindles were less ordered
      than the spindle of wild-type cells. The number of noncore microtubules was
      significantly higher than that reported for wild-type, and these microtubules did
      not display a characteristic metaphase configuration. cdc20 spindles showed
      significantly more cross-bridges between spindle microtubules than were seen in
      the wild type. The cross-bridge density was highest between antiparallel
      microtubules. These data suggest that spindle microtubules are stabilized in
      cdc20 cells and that the CDC20 gene product may be involved in cell cycle
      processes that promote spindle microtubule disassembly.

PMID- 9017592
TI  - Transport through the yeast endocytic pathway occurs through morphologically
      distinct compartments and requires an active secretory pathway and Sec18p/N
      ethylmaleimide-sensitive fusion protein.
AB  - Molecules travel through the yeast endocytic pathway from the cell surface to the
      lysosome-like vacuole by passing through two sequential intermediates.
      Immunofluorescent detection of an endocytosed pheromone receptor was used to
      morphologically identify these intermediates, the early and late endosomes. The
      early endosome is a peripheral organelle that is heterogeneous in appearance,
      whereas the late endosome is a large perivacuolar compartment that corresponds to
      the prevacuolar compartment previously shown to be an endocytic intermediate. We
      demonstrate that inhibiting transport through the early secretory pathway in sec
      mutants quickly impedes transport from the early endosome. Treatment of sensitive
      cells with brefeldin A also blocks transport from this compartment. We provide
      evidence that Sec18p/N-ethylmaleimide-sensitive fusion protein, a protein
      required for membrane fusion, is directly required in vivo for forward transport
      early in the endocytic pathway. Inhibiting protein synthesis does not affect
      transport from the early endosome but causes endocytosed proteins to accumulate
      in the late endosome. As newly synthesized proteins and the late steps of
      secretion are not required for early to late endosome transport, but endoplasmic
      reticulum through Golgi traffic is, we propose that efficient forward transport
      in the early endocytic pathway requires delivery of lipid from secretory
      organelles to endosomes.

PMID- 9017593
TI  - In vitro reconstitution of a heterotrimeric nucleoporin complex consisting of
      recombinant Nsp1p, Nup49p, and Nup57p.
AB  - The yeast nucleoporins Nsp1p, Nup49p, and Nup57p form a complex at the nuclear
      pores which is involved in nucleocytoplasmic transport. To investigate the
      molecular basis underlying complex formation, recombinant full-length Nup49p and
      Nup57p and the carboxyl-terminal domain of Nsp1p, which lacks the FXFG repeat
      domain, were expressed in Escherichia coli. When the three purified proteins were
      mixed together, they spontaneously associated to form a 150-kDa complex of 1:1:1
      stoichiometry. In this trimeric complex, Nup57p fulfills the role of an
      organizing center, to which Nup49p and Nsp1p individually bind. For this
      interaction to occur, only two heptad repeat regions of the Nsp1p carboxyl
      terminal domain are required, each region being about 50 amino acids in length.
      Finally, the reconstituted complex has the capability to bind to full-length
      Nic96p but not to mutant forms which also do not interact in vivo. When added to
      permeabilized yeast cells, the complex associates with the nuclear envelope and
      the nuclear pores. We conclude that Nsp1p, Nup49p, and Nup57p can reconstitute a
      complex in vitro which is competent for further assembly with other components of
      nuclear pores.

PMID- 9017594
TI  - Major histocompatibility complex class I molecules mediate association of SV40
      with caveolae.
AB  - Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated
      plasma membrane invaginations. Viral particles subsequently appear within the
      endoplasmic reticulum. In the present study, we have examined the surface binding
      and internalization of SV40 by immunoelectron microscopy. We show that SV40
      associates with surface pits which have the characteristics of caveolae and are
      labeled with antibodies to the caveolar marker protein, caveolin-1. SV40 is
      believed to use major histocompatibility complex (MHC) class I molecules as cell
      surface receptors. Using a number of MHC class I-specific monoclonal antibodies,
      we found that both viral infection and association of virus with caveolae were
      strongly reduced by preincubation with anti-MHC class I antibodies. Because
      binding of SV40 to MHC class I molecules may induce clustering, we investigated
      whether antibody cross-linked class I molecules also redistributed to caveolae.
      Clusters of MHC class I molecules were indeed shown to be specifically associated
      with caveolin-labeled surface pits. Taken together, the results suggest that SV40
      may make use of MHC class I molecule clustering and the caveolae pathway to enter
      mammalian cells.

PMID- 9017595
TI  - Fibroblasts contracting collagen matrices form transient plasma membrane passages
      through which the cells take up fluorescein isothiocyanate-dextran and Ca2+.
AB  - When fibroblasts contract collagen matrices, the cells activate a Ca(2+)
      dependent cyclic AMP signaling pathway. We have found that contraction also
      stimulates uptake of fluorescein isothiocyanate-dextran molecules from the
      medium. Our results indicate that fluorescein isothiocyanate-dextran enters
      directly into the cell cytoplasm through 3- to 5-nm plasma membrane passages.
      These passages, which reseal in less than 5 s in the presence of divalent
      cations, also are likely sites of Ca2+ uptake during contraction and the first
      step in contraction-activated cyclic AMP signaling. The formation of plasma
      membrane passages during fibroblast contraction may reflect a general cellular
      response to rapid mechanical changes.

PMID- 9017596
TI  - Coiled bodies without coilin.
AB  - Nuclei assembled in vitro in Xenopus egg extract contain coiled bodies that have
      components from three different RNA processing pathways: pre-mRNA splicing, pre
      rRNA processing, and histone pre-mRNA 3'-end formation. In addition, they contain
      SPH-1, the Xenopus homologue of p80-coilin, a protein characteristic of coiled
      bodies. To determine whether coilin is an essential structural component of the
      coiled body, we removed it from the egg extract by immunoprecipitation. We showed
      that nuclei with bodies morphologically identical to coiled bodies (at the light
      microscope level) formed in such coilin-depleted extract. As expected, these
      bodies did not stain with antibodies against coilin. Moreover, they failed to
      stain with an antibody against the Sm proteins, although Sm proteins associated
      with snRNAs were still present in the extract. Staining of the coilin- and Sm
      depleted coiled bodies was normal with antibodies against two nucleolar proteins,
      fibrillarin and nucleolin. Similar results were observed when Sm proteins were
      depleted from egg extract: staining of the coiled bodies with antibodies against
      the Sm proteins and coilin was markedly reduced but bright nucleolin and
      fibrillarin staining remained. These immunodepletion experiments demonstrate an
      interdependence between coilin and Sm snRNPs and suggest that neither is
      essential for assembly of nucleolar components in coiled bodies. We propose that
      coiled bodies are structurally heterogeneous organelles in which the components
      of the three RNA processing pathways may occur in separate compartments.

PMID- 9017597
TI  - Interaction of a Dictyostelium member of the plastin/fimbrin family with actin
      filaments and actin-myosin complexes.
AB  - A protein purified from cytoskeletal fractions of Dictyostelium discoideum proved
      to be a member of the fimbrin/plastin family of actin-bundling proteins. Like
      other family members, this Ca(2+)-inhibited 67-kDa protein contains two EF hands
      followed by two actin-binding sites of the alpha-actinin/beta-spectrin type. Dd
      plastin interacted selectively with actin isoforms: it bound to D. discoideum
      actin and to beta/gamma-actin from bovine spleen but not to alpha-actin from
      rabbit skeletal muscle. Immunofluorescence labeling of growth phase cells showed
      accumulation of Dd plastin in cortical structures associated with cell surface
      extensions. In the elongated, streaming cells of the early aggregation stage, Dd
      plastin was enriched in the front regions. To examine how the bundled actin
      filaments behave in myosin II-driven motility, complexes of F-actin and Dd
      plastin were bound to immobilized heavy meromyosin, and motility was started by
      photoactivating caged ATP. Actin filaments were immediately propelled out of
      bundles or even larger aggregates and moved on the myosin as separate filaments.
      This result shows that myosin can disperse an actin network when it acts as a
      motor and sheds light on the dynamics of protein-protein interactions in the
      cortex of a motile cell where myosin II and Dd plastin are simultaneously
      present.

PMID- 9017598
TI  - An abundant nucleolar phosphoprotein is associated with ribosomal DNA in
      Tetrahymena macronuclei.
AB  - An abundant 52-kDa phosphoprotein was identified and characterized from
      macronuclei of the ciliated protozoan Tetrahymena thermophila. Immunoblot
      analyses combined with light and electron microscopic immunocytochemistry
      demonstrate that this polypeptide, termed Nopp52, is enriched in the nucleoli of
      transcriptionally active macronuclei and missing altogether from
      transcriptionally inert micronuclei. The cDNA sequence encoding Nopp52 predicts a
      polypeptide whose amino-terminal half consists of multiple acidic/serine-rich
      regions alternating with basic/proline-rich regions. Multiple serines located in
      these acidic stretches lie within casein kinase II consensus motifs, and Nopp52
      is an excellent substrate for casein kinase II in vitro. The carboxyl-terminal
      half of Nopp52 contains two RNA recognition motifs and an extreme carboxyl
      terminal domain rich in glycine, arginine, and phenylalanine, motifs common in
      many RNA processing proteins. A similar combination and order of motifs is found
      in vertebrate nucleolin and yeast NSR1, suggesting that Nopp52 is a member of a
      family of related nucleolar proteins. NSR1 and nucleolin have been implicated in
      transcriptional regulation of rDNA and rRNA processing. Consistent with a role in
      ribosomal gene metabolism, rDNA and Nopp52 colocalize in situ, as well as by
      cross-linking and immunoprecipitation experiments, demonstrating an association
      between Nopp52 and rDNA in vivo.

PMID- 9017599
TI  - Investigation of the mechanism of retraction of the cell margin and rearward flow
      of nodules during mitotic cell rounding.
AB  - We have studied two types of cell motility directed toward the cell center:
      retraction of the cell margin and rearward flow of small cytoplasmic nodules
      during mitotic cell rounding in Potoroo tridactylis kidney (PtK2) cells by time
      lapse video microscopy, drug treatments, and photoactivation of fluorescence.
      Nodules flow rearward on thin, actin-rich fibers (retraction fibers) exposed as
      the cell margin retracts. Retraction of the cell margin and rearward flow of
      nodules require intact actin filaments, but are insensitive to an inhibitor of
      myosin function (butanedione monoxime). Using photoactivation of fluorescence
      marking, we have determined that actin filaments in the majority of retraction
      fibers remain stationary while the cell margin retracts and nodules flow
      rearward. The pointed ends of retraction fiber actin filaments face the cell
      center. We argue that nodule motility is driven by a novel actin-based force that
      perhaps also partially contributes to retraction of the cell margin during cell
      rounding at mitosis.

PMID- 9017600
TI  - Role of gelsolin in actin depolymerization of adherent human neutrophils.
AB  - Human neutrophils generally function adherent to an extracellular matrix. We have
      previously reported that upon adhesion to laminin- or fibronectin-coated, but not
      uncoated, plastic there is a depolymerization of actin in neutrophils. This
      phenomenon was not affected by inhibitors of the more well-studied components of
      the signal transduction pathway, specifically, pertussis toxin, an inhibitor of G
      proteins, H-7 or staurosporine, inhibitors of protein kinase C, or herbimycin A,
      an inhibitor of nonreceptor tyrosine kinase. We therefore focused our attention
      on actin-binding proteins and measured the changes in the partitioning of
      gelsolin between the Triton X-100-soluble and -insoluble cellular fractions which
      occur upon neutrophil adhesion by means of quantitating anti-gelsolin antibody
      binding to aliquots of these fractions. It was found that approximately 90% of
      the total cellular gelsolin was found in the Triton X-100-soluble fraction in
      suspended cells, but that upon adherence to either fibronectin- or laminin-coated
      plastic about 40% of the soluble gelsolin could be detected in the insoluble
      fraction. This effect was not observed in cells adherent to uncoated plastic,
      wherein more than 90% of the gelsolin was found in the soluble fraction. Results
      of immunofluorescence microscopy of these cell preparations was consistent with
      this data. A gelsolin translocation to the insoluble cellular actin network may
      account for a part of the observed actin depolymerization.

PMID- 9017601
TI  - Subcellular analysis of Ca2+ homeostasis in primary cultures of skeletal muscle
      myotubes.
AB  - Specifically targeted aequorin chimeras were used for studying the dynamic
      changes of Ca2+ concentration in different subcellular compartments of
      differentiated skeletal muscle myotubes. For the cytosol, mitochondria, and
      nucleus, the previously described chimeric aequorins were utilized; for the
      sarcoplasmic reticulum (SR), a new chimera (srAEQ) was developed by fusing an
      aequorin mutant with low Ca2+ affinity to the resident protein calsequestrin. By
      using an appropriate transfection procedure, the expression of the recombinant
      proteins was restricted, within the culture, to the differentiated myotubes, and
      the correct sorting of the various chimeras was verified with immunocytochemical
      techniques. Single-cell analysis of cytosolic Ca2+ concentration ([Ca2+]c) with
      fura-2 showed that the myotubes responded, as predicted, to stimuli known to be
      characteristic of skeletal muscle fibers, i.e., KCl-induced depolarization,
      caffeine, and carbamylcholine. Using these stimuli in cultures transfected with
      the various aequorin chimeras, we show that: 1) the nucleoplasmic Ca2+
      concentration ([Ca2+]n) closely mimics the [Ca2+]c, at rest and after
      stimulation, indicating a rapid equilibration of the two compartments also in
      this cell type; 2) on the contrary, mitochondria amplify 4-6-fold the [Ca2+]c
      increases; and 3) the lumenal concentration of Ca2+ within the SR ([Ca2+]sr) is
      much higher than in the other compartments (> 100 microM), too high to be
      accurately measured also with the aequorin mutant with low Ca2+ affinity. An
      indirect estimate of the resting value (approximately 1-2 mM) was obtained using
      Sr2+, a surrogate of Ca2+ which, because of the lower affinity of the
      photoprotein for this cation, elicits a lower rate of aequorin consumption. With
      Sr2+, the kinetics and amplitudes of the changes in [cation2+]sr evoked by the
      various stimuli could also be directly analyzed.

PMID- 9017602
TI  - Involvement of in situ conformation of ribosomal genes and selective distribution
      of upstream binding factor in rRNA transcription.
AB  - The distribution of the ribosomal genes (rDNA) and the upstream binding factor
      (UBF), correlatively with their RNA transcripts, was investigated in G1, S-phase,
      and G2. rDNA was distributed in nucleoli, with alternate sites of clustered and
      dispersed genes. UBF was found associated with some but not all clustered genes
      and proportionally more with dispersed genes. It was distributed in several foci
      that were more numerous and heterogeneous in size during G2 than G1. We suggest
      that UBF associated with rDNA during S-phase because its nucleolar amount
      increased during that time and remained stable in G2. 5,6-Dichloro-1-beta-D
      ribofuranosylbenzimidazole treatment indicated a similar amount of UBF per
      transcription unit, and consequently heterogeneous size of the UBF foci can
      represent a variable number of transcription units per foci. Direct visualization
      of the transcripts demonstrated that only part of UBF is associated with active
      transcription and that rDNA distribution varied with transcription. We propose
      that in the same rDNA locus three types of configuration coexist that are
      correlated with gene activity: 1) clustered genes without UBF; 2) clustered genes
      with UBF, of which some are associated with transcription; and 3) dispersed genes
      with UBF and transcription. These results support the hypothesis that rDNA
      transcription involved several steps of regulation acting successively and
      locally in the same locus to promote the repressed clustered genes to become
      actively transcribed dispersed genes.

PMID- 9017603
TI  - Calcineurin-dependent nuclear translocation of a murine transcription factor
      NFATx: molecular cloning and functional characterization.
AB  - Members of the nuclear factor of activated T cells (NFAT) are involved in the
      induction of a number of cytokine genes. We report here cDNA cloning and
      chromosomal localization of a murine homologue of human NFATx, designated as
      mNFATx1, and its splicing variants mNFATx2 and m delta NFATx. Northern blot
      analysis showed mNFATx1 to be predominantly expressed in the thymus. mNFATx1, but
      not m delta NFATx, produced in COS-7 cells, bound to all NFAT-binding sites of
      the interleukin (IL)-2 and IL-4 promoters tested. Immunofluorescence assay showed
      that both mNFATx1 and m delta NFATx introduced into COS-7 cells localized
      predominantly to the cytoplasm, but did translocate to the nucleus, either by
      cotransfection with an active form of calcineurin or wild-type calcineurin
      followed by stimulation with calcium ionophore. Translocation of mNFATx1
      correlated well with activation of the murine IL-2 promoter; mNFATx1 translocated
      under conditions described above, in combination with phorbol 12-myristate 13
      acetate, activated the transiently transfected murine IL-2 promoter. Thus,
      nuclear-translocated mNFATx1 is involved in activation of the IL-2 promoter.
      These results provide the first evidence for the requirement of calcineurin in
      the control of mNFATx imported from the cytoplasm to the nucleus and implies that
      mNFATx may possibly be a substrate of calcineurin in vivo.

PMID- 9017605
TI  - Is the level of arterial pressure reduction important for preservation of renal
      function.

PMID- 9017606
TI  - Colour Doppler sonography to screen for renal artery stenosis--technical points
      to consider.

PMID- 9017608
TI  - Hyperhomocyst(e)inaemia in renal failure--what are the implications?

PMID- 9017607
TI  - Ochratoxin a: a new environmental factor which is toxic for the kidney?

PMID- 9017609
TI  - Haemodialysis access without thrombosis: is it possible?

PMID- 9017610
TI  - Systematic reviews and their roles in promoting evidence-based medicine in renal
      disease.

PMID- 9017604
TI  - Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are
      encoded by two multicopy suppressors of nin1-1.
AB  - Nin1p, a component of the 26S proteasome of Saccharomyces cerevisiae, is required
      for activation of Cdc28p kinase at the G1-S-phase and G2-M boundaries. By
      exploiting the temperature-sensitive phenotype of the nin1-1 mutant, we have
      screened for genes encoding proteins with related functions to Nin1p and have
      cloned and characterized two new multicopy suppressors, SUN1 and SUN2, of the
      nin1-1 mutation. SUN1 can suppress a null nin1 mutation, whereas SUN2, an
      essential gene, does not. Sun1p is a 268-amino acid protein which shows strong
      similarity to MBP1 of Arabidopsis thaliana, a homologue of the S5a subunit of the
      human 26S proteasome. Sun1p binds ubiquitin-lysozyme conjugates as do S5a and
      MBP1. Sun2p (523 amino acids) was found to be homologous to the p58 subunit of
      the human 26S proteasome. cDNA encoding the p58 component was cloned.
      Furthermore, expression of a derivative of p58 from which the N-terminal 150
      amino acids had been removed restored the function of a null allele of SUN2.
      During glycerol density gradient centrifugation, both Sun1p and Sun2p comigrated
      with the known proteasome components. These results, as well as other structural
      and functional studies, indicate that both Sun1p and Sun2p are components of the
      regulatory module of the yeast 26S proteasome.

PMID- 9017611
TI  - Vancomycin resistant enterococci--a threat to the nephrologist on the horizon?
      Glycopeptide-resistant enterococci and ICDC-recommendations for a limited use of
      glycopeptides.

PMID- 9017612
TI  - Analgesic nephropathy.

PMID- 9017613
TI  - Is it worth performing kidney replacement therapy on patients Over 80?

PMID- 9017614
TI  - Acute renal failure in falciparum malaria--increasing prevalence in some areas of
      India--a need for awareness.
AB  - Twenty-six cases (4.8%) from a total of 540 patients with acute renal failure
      (ARF) of diverse aetiology had ARF in association with falciparum malaria. Their
      ages ranged from 15 to 85 years (mean 31.2). Urinary sediment abnormalities and
      proteinuria (less than 1 g/24 h) were observed in 15 (57.7%) cases. The probable
      underlying factors leading to ARF were: volume depletion 17 (65.3%),
      intravascular haemolysis 8 (30.8%), hyperparasitaemia 8 (30.8%), cholestatic
      jaundice 6 (23%), and hypotension 5 (19.2%). Dialysis therapy was required in 15
      patients (57.7%) as they had severe renal failure, and the remaining 11 patients
      improved with supportive measures. All patients received antimalarial therapy.
      The clinical course of ARF was consistent with acute tubular necrosis in 20
      patients. Six cases were subjected to percutaneous renal biopsy. One patient
      showed histological features of necrotizing glomerulonephritis along with acute
      tubulointerstitial nephritis. The biopsies in the other five patients showed
      features of acute tubular necrosis in three, and acute interstitial oedema with
      patchy tubular necrosis in two. The mortality rate was 30.8%. Thus falciparum
      malaria, which has been an important cause of ARF in certain highly endemic zones
      of India, is showing an increasing prevalence in other parts such as Eastern
      Uttar Pradesh due to an imbalance between the increasing population and
      inadequate sanitary facilities, which further worsen during floods.

PMID- 9017615
TI  - Late diagnosis of chronic renal failure and mortality on maintenance dialysis.
AB  - BACKGROUND: Recent observations in our country have shown that late diagnosis of
      chronic renal failure (CRF) is an important cause of late referral and late
      commencement of maintenance dialysis. We prospectively investigated the influence
      of late diagnosis of CRF on patient mortality during dialysis therapy. METHODS:
      Among 184 consecutive patients with nondiabetic end-stage renal disease starting
      chronic dialysis at the Federal University Hospital in the city of Sao Paulo, 106
      had a late diagnosis of CRF (less than 1 month before starting dialysis) and 78
      had an early diagnosis. During the first 6 months of dialysis treatment, patient
      survival was compared in the two groups, using the Kaplan-Meier method and the
      Cox proportional hazards model. RESULTS: Six-month patient survival rate was
      lower in the late than in the early diagnosis group (69% versus 87%, P < 0.01).
      In the late diagnosis group, the hazard ratio of mortality was 2.77 (95% CI, 1.36
      5.66) times that of the early diagnosis group. In a multivariate analysis, after
      adjusting for age, comorbid illness, and serum biochemical measurements, time of
      diagnosis did not remain significantly associated with mortality risk. In this
      analysis, age, pulmonary infection, and low serum albumin were significant
      predictors of mortality. CONCLUSIONS: Patients with a late diagnosis have a
      higher mortality risk during the first 6 months of maintenance dialysis. This
      increased risk is related to comorbid conditions, some of which could be
      prevented by predialysis care. Interventions to promote early diagnosis of CRF
      and adequate predialysis follow-up need to be evaluated if the survival of
      patients with chronic renal failure is to improve.

PMID- 9017616
TI  - Correlation between glomerular morphology and renal haemodynamic response to
      amino-acid administration in patients with IgA nephropathy.
AB  - RATIONALE: To establish relationship, if any, between renal morphology and renal
      haemodynamic response to amino acids. DESIGN AND METHODS: We investigated the
      correlation between renal haemodynamic regulation and morphology in a group of 15
      patients with primary IgA nephropathy (IgAN) (age 26 +/- 2 years, BMI 24.4 +/- 1,
      GFR 64 +/- 5 ml/min, RPF 377 +/- 34 ml/min, FF 0.17 +/- 0.02). Twelve normal
      subjects (age 30 +/- 3 years, BMI 24 +/- 1, GFR 82 +/- 6 ml/min, RPF 421 +/- 42
      ml/min, FF 0.19 +/- 0.02) were studied as controls. IgA patients were divided
      into two groups according to the histological staging of glomerular lesions:
      group I (n = 7) stage II, and group II (n = 8) stage III-IV. RESULTS: In the
      basal state GFR was similar in the two groups and averaged 64 +/- 9 and 64 +/- 6
      ml/min respectively. In contrast, FF was significantly lower in group II (0.14 +/
      0.01) (P < 0.05) in comparison to group I (0.21 +/- 0.03) and controls (0.19 +/-
      0.02). In order to evaluate the renal functional reserve, all study groups
      underwent to an intravenous amino-acid infusion designed to increase plasma amino
      acid levels twofold (total from 2096 +/- 145 to 4301 +/- 221 mumol/l in IgA
      nephropathy patients and from 2272 +/- 83 to 3844 +/- 238 mumol/l in controls).
      In response to amino-acid infusion, GFR rose significantly in group I (GFR 20 +/-
      2% and RPF 37 +/- 4% versus basal) and controls (GFR 20 +/- 2% and RPF 20 +/- 3%
      versus basal) (both P < 0.01 vs basal). In contrast, in patients with more severe
      glomerular lesions (group II) neither GFR nor RPF rose significantly (GFR -1 +/-
      4% and RPF -8 +/- 6% versus basal) (P NS versus basal, P < 0.01 versus group I
      and controls). CONCLUSIONS: The data show that in IgA nephropathy: severe forms
      of glomerular lesions are associated with a complex alteration of glomerular
      haemodynamic regulation, characterized by lower basal FF and loss of haemodynamic
      response to hyperaminoacidaemia.

PMID- 9017617
TI  - Does the presence of ANCA in patients with ulcerative colitis necessarily imply
      renal involvement?
AB  - BACKGROUND: ANCA are thought to play a pathogenic role in renal vasculitis. ANCA
      may also be detected in patients with diseases not usually associated with renal
      pathology, such as ulcerative colitis. Our study was conducted to determine if
      the presence of ANCA in patients with ulcerative colitis is associated with renal
      pathology. METHODS: Eight ANCA-positive and five ANCA-negative patients with a
      histological and endoscopic diagnosis of active ulcerative colitis were
      investigated. Repeated complete urinalyses and determination of microalbuminuria
      and creatinine clearance were performed. Serum IgG and IgA ANCA were evaluated in
      all patients by indirect immunofluorescence and ELISA, and when detected the
      antibodies were further characterized by alpha granules preparation,
      myeloperoxidase, lactoferrin, and cathepsin G. RESULTS: In both ANCA-positive and
      ANCA-negative patients renal function was normal or near normal and urinalyses
      (including microalbuminuria) failed to disclose any abnormalities. ANCA exhibited
      a perinuclear pattern in all ANCA-positive patients. Interestingly, none of the
      ANCA-positive patients had antibodies to myeloperoxidase or to alpha granules
      which are usually found in the sera of patients with ANCA-associated vasculitis,
      and only one had antibodies to lactoferrin. The ANCA specificity remained
      undetermined in the remaining seven patients. At the end of the 1-year
      observation period, all ANCA-positive patients remained ANCA-positive without
      developing symptoms, signs or laboratory abnormalities consistent with renal
      involvement. CONCLUSIONS: Renal damage was not observed in ANCA-positive patients
      with ulcerative colitis even after 1 year of follow-up, suggesting that the ANCA
      found in these patients do not share the antigenic targets with the ANCA commonly
      found in renal vasculitis. Therefore the potential of ANCA of inducing renal
      lesions (if any) is dependent on their own antigenic specificity.

PMID- 9017618
TI  - Biochemical markers for non-invasive diagnosis of hyperparathyroid bone disease
      and adynamic bone in patients on haemodialysis.
AB  - The diagnostic and predictive value of serum intact parathyroid hormone (iPTH)
      and osteocalcin (bone Gla protein, BGP), alone or in combination, have been
      examined in only a small number of haemodialysis patients. METHODS: We studied
      prospectively 114 patients (46 women, 68 men; mean age 52 +/- 12 years) on
      regular haemodialysis for a mean of 55 (6-185) months. All patients underwent
      labelled transiliac bone biopsy, and serum levels of iPTH, BGP and alkaline
      phosphatase were determined. RESULTS: Seventy-one patients (62%) showed
      histological findings of hyperparathyroid bone disease, 24 (21%) mixed bone
      disease, six (5.5%) osteomalacia and 13 (11.5%) adynamic bone. Bone aluminium
      deposition over more than 25% of the trabecular bone interface was found in 66
      patients (58%). Serum iPTH and BGP correlated with the majority of
      histomorphometric indices of bone formation, mineralization and resorption (r >
      0.5, P < 0.01). iPTH levels > or = 200 pg/ml and BGP > or = 50 ng/ml were found
      to be indicative of hyperparathyroid bone disease, whilst iPTH levels < 65 pg/ml
      and BGP < 20 ng/ml were indicative of adynamic bone. However, the positive
      predictive value of these indices was limited (less than 80%), although their
      negative predictive value, especially when used in combination, was good (more
      than 90%) and the exclusion of hyperparathyroid bone disease and adynamic bone
      was possible. The diagnostic and predictive value of these bone markers were
      improved when patients with bone aluminium deposition were excluded. CONCLUSIONS:
      Diagnosis of hyperparathyroid bone disease and adynamic bone is difficult on the
      basis of iPTH and BGP, especially when bone aluminium deposition is prevalent.
      However, using these bone markers, preferably in combination, the exclusion of
      these lesions is feasible.

PMID- 9017619
TI  - Uraemic pruritus and exposure to di(2-ethylhexyl) phthalate (DEHP) in
      haemodialysis patients.
AB  - Uraemic pruritus is a frequent and disabling symptom in patients on dialysis. The
      pathogenesis of uraemic pruritus is nevertheless still obscure. We investigated
      whether di(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer in
      polyvinylchloride (PVC) haemodialysis tubings, is a possible pathogenetic factor
      in uraemic pruritus. Serum concentrations of DEHP and its major derivatives mono
      (2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH) and phthalic acid (PA) were
      determined in uraemic patients before and after a haemodialysis session and
      compared with the occurrence and intensity of pruritus in these patients. Twenty
      one patients on regular haemodialysis for at least 6 months were examined. The
      severity of uraemic pruritus was assessed using a standard questionnaire
      (pruritus score). The quantitative analysis of DEHP and its derivatives was
      carried out by GC/selected ion monitoring mass spectrometry. Fourteen out of 21
      patients (66%) complained about uraemic pruritus to a variable degree. The post
      dialysis serum concentrations of DEHP, MEHP and 2-EH were significantly higher
      than the corresponding pre-dialysis values, whereas the post-dialysis
      concentrations of PA (0.122 +/- 0.078 microgram/microliter) were significantly
      lower than pre-dialysis levels (0.194 +/- 0.101 microgram/microliter, P =
      0.00068). Neither pre- nor post-dialysis serum concentrations of DEHP, MEHP, PA
      or 2-EH were correlated with the severity of uraemic pruritus. Additionally,
      serum concentrations of DEHP and its metabolites did not differ significantly in
      patients with and without pruritus. These findings suggest that patients on
      haemodialysis are regularly exposed to considerable amounts of DEHP and
      metabolites. Phthalic acid, one of the presumed end products of DEHP metabolism,
      might be eliminated at least in part by haemodialysis. The exposition to DEHP and
      metabolites during haemodialysis, as assessed by measuring serum concentrations,
      bears no immediate relation to the occurrence or intensity of uraemic pruritus.

PMID- 9017620
TI  - Inverse relationships between haemoglobin and ristocetin-induced platelet
      aggregation in haemodialysis patients under erythropoietin therapy.
AB  - BACKGROUND: Amelioration of the anaemia of chronic renal failure and subsequent
      improved haemorheology result in correction of bleeding diathesis as evidenced by
      shortening of the skin bleeding time (BT). However, the relationship between the
      haematocrit and platelet-vessel wall interactions in haemodialysis (HD) patients
      under recombinant human erythropoietin (rHuEpo) therapy, assessed by platelet
      aggregation in response to ristocetin is more complex and somewhat inconsistent.
      METHODS: We investigated the relationship between haemoglobin (Hb) levels and
      whole blood ristocetin-induced platelet aggregation (electric impedance method)
      in 28 HD patients treated with rHuEpo, and with normal BT. The measurements were
      repeated in 16 subjects after having reduced platelet aggregability with orally
      administered ketanserin. RESULTS: Ristocetin-induced platelet aggregation in the
      whole group was comparable to those found in 21 age-matched healthy subjects
      (normals) and in 25 HD patients not treated with rHuEpo (uraemics).
      Interestingly, a significant inverse correlation between this aggregation and Hb
      concentration was found (r = -0.392, P < 0.05). In the group of 16 patients, the
      pre-ketanserin aggregation was more intensive than in the normals and uraemics (P
      < 0.05). Ketanserin produced a fall in ristocetin-induced platelet aggregation (P
      < 0.02), prolongation of the BT (P < 0.02) and, unexpectedly, a decrease in serum
      Epo concentration (P < 0.0002) and the Hb level (P < 0.001). Again, an inverse
      correlation between depressed ristocetin-induced platelet aggregation and lowered
      Hb concentration was found (r = -0.590, P < 0.02). Moreover, a strong positive
      correlation between the extent of preketanserin platelet aggregation and the
      decrease in the intensity of this process that followed the trial was observed (r
      = 0.919, P < 0.000005). There were no changes in other haematological parameters
      or arterial blood pressure. CONCLUSIONS: Considering the role of von Willebrand
      factor and fibrinogen in mediating ristocetin-induced platelet aggregation, and
      enhanced synthesis and/or release of these macromolecules in response to uraemia
      or inflammation, we suggest that exaggerated whole-blood platelet aggregability
      to ristocetin points to blunted erythropoiesis in HD patients on rHuEpo therapy.

PMID- 9017621
TI  - Concentration of dimethyl-L-arginine in the plasma of patients with end-stage
      renal failure.
AB  - Abstract. NGNG dimethyl-L-arginine (asymmetric dimethyl-L-arginine; ADMA) and
      NGNG dimethyl-L-arginine (symmetric dimethyl-L-arginine; SDMA) are naturally
      occurring analogues of L-arginine, the substrate for nitric oxide (NO) synthesis.
      ADMA is a potent inhibitor of NO synthesis, and accumulates in the plasma of
      patients with renal failure. However the precise concentration of ADMA and SDMA
      in renal patients is still controversial. This study was performed to measure
      plasma ADMA and SDMA concentrations by two different HPLC techniques in nine
      healthy controls and 10 uraemic subjects, and to investigate the effects of
      haemodialysis. In controls, the mean (+/-SEM) plasma concentrations of ADMA and
      SDMA were 0.36 +/- 0.09 and 0.39 +/- 0.05 mumol/l respectively, yielding an
      ADMA/SDMA ratio of 1.2 +/- 0.17. In uraemic patients, the plasma concentrations
      of ADMA and SDMA were 0.9 +/- 0.08 mumol/l (P < 0.001 compared to controls) and
      3.4 +/- 0.3 mumol/l (P < 0.001 compared to controls) with an ADMA/SDMA ratio of
      0.27 +/- 0.015 (P < 0.001). In the course of one 4 h haemodialysis session, ADMA
      concentrations decreased from 0.99 +/- 0.13 to 0.77 +/- 0.3 mumol/l and SDMA
      concentrations from 3.38 +/- 0.44 to 2.27 +/- 0.21 mumol/l. The plasma
      ADMA/creatinine ratio tended to increase from 1.26 +/- 0.20 x 10(-3) to 2.01 +/-
      0.41 x 10(-3). It is concluded that there is a modest (3-fold) but definite
      increase in plasma ADMA concentration in uraemic patients compared to controls.
      SDMA accumulates to a greater degree (8-fold increase) and more closely parallels
      creatinine concentration than ADMA. The change in the ADMA/SDMA ratio is not
      accounted for by greater renal or dialysis clearance of ADMA, and, even though
      alternative explanations are not excluded, greater metabolism of ADMA than SDMA
      is the most likely explanation. Although small in magnitude, the increase in ADMA
      concentration might by biologically significant.

PMID- 9017622
TI  - Activation of human neutrophils after contact with cellulose-based haemodialysis
      membranes: intracellular calcium signalling in single cells.
AB  - PURPOSE OF STUDY: In vitro contact of human leukocytes with cellulose-based
      dialysis membranes under complement-independent conditions results in activation
      of various leukocyte functions. To analyse signals involved in the mechanism of
      cell activation, we measured changes in cytosolic free calcium ([Ca2+]i) in
      individual human blood neutrophils (PMN) upon contact with flat sheet
      haemodialysis membranes. RESULTS: By confocal laser-scanning microscopy (CLSM),
      changes in [Ca2+]i were monitored in Fluo-3-labelled cells up to 10 min after
      contact with a regenerated cellulose (RC) membrane. Multiple [Ca2+]i transients
      were observed for cells in contact with RC; biostochastic analysis showed that up
      to 67% of the PMN responded with a high increase in [Ca2+]i, the rest were low-
      or non-responding cells. After contact with the new synthetic polycarbonate
      polyether (PC-PE) membrane only non-responding cells were seen, indicating
      reduced cellular contact activation. The increase in [Ca2+]i of cells on RC could
      be inhibited by 5mM L-fucose. This monosaccharide was recently found to be
      present in cellulose-based polymers in picomolar concentrations. CONCLUSIONS: The
      data supports the hypothesis that dialysis-membrane-associated L-fucose residues
      participate in complement-independent leukocyte activation during haemodialysis
      therapy.

PMID- 9017623
TI  - Monoclonal gammopathy after intense induction immunosuppression in renal
      transplant patients.
AB  - OBJECTIVES: Incidence and risk factors of post-transplant monoclonal gammopathy
      were studied in renal transplant patients who received their grafts between 1982
      and 1992 (n = 390 grafts). Immunoelectrophoresis was performed at annual
      intervals after transplantation. RESULTS: Forty-six cases of clonal gammopathy
      were detected: 35 monoclonal, 11 bi- or triclonal, with a predominance of IgG and
      kappa light-chain subtypes (IgG, 39; IgA, 3; IgM, 4; kappa, 35; lambda, 19).
      Gammopathy was incidence of gammopathy was 10.7%, much higher than expected for a
      group of similar age from the general population. Thirty of the 46 gammopathies
      appeared within the first 2 years of transplantation. Gammopathy never progressed
      to multiple myeloma during follow-up (median 1 year; (range 0-10)); one patient
      subsequently developed Kaposi sarcoma. The 2-year incidence of gammopathy was
      much higher in patients transplanted in 1989-1991 (23/142) than in 1982-1988
      (7/248) (P < 0.0001). This coincided with the use of quadruple induction
      immunosuppression (cyclosporin A+azathioprine+prednisone plus either ATG
      fresenius (ATG-F) or OKT3) since 1989. The risk for acquiring gammopathy within 2
      years of transplantation was 14.7% (95% CI 9.2, 20.3%) in patients receiving
      quadruple induction therapy, but only 3.0% (CI 1.2, 6.1%) without such therapy (P
      < 0.0001). The risk for patients receiving quadruple immunosuppression with OKT3
      was 24.5%, significantly greater than with ATG-F (11.8%, P < 0.05). Discriminant
      analysis revealed that the type of immunosuppression, but not age or year of
      transplantation, were independent risk factors for gammopathy. CONCLUSION:
      Monoclonal gammopathy frequently occurs after renal transplantation. Risks are
      higher for patients receiving quadruple induction immunosuppression, particularly
      if it includes OKT3. Follow-up of these patients is warranted for the early
      detection of malignant transformation.

PMID- 9017624
TI  - Peritoneal nitric oxide is a marker of peritonitis in patients on continuous
      ambulatory peritoneal dialysis.
AB  - Nitric oxide plays an important role in mediating the inflammatory process. The
      aim of this study was to evaluate if nitric oxide production was increased during
      peritonitis in patients receiving continuous ambulatory peritoneal dialysis
      (CAPD), and the association with the prognosis. The study population comprised 21
      patients with 22 episodes of peritonitis. Fifteen patients without peritonitis
      were controls. Nitrate was measured by HPLC and nitrite by the Griess method, to
      reflect nitric oxide production. Peritoneal dialysate effluent and plasma were
      collected from six patients during peritonitis and 1 week after treatment to
      study changes in dialysate:plasma ratio. In 15 patients, nitrite was measured
      during peritonitis and every 3 days for 2 weeks or until normalized for
      evolutional changes. The dialysate:plasma ratios of nitrate and nitrite during
      peritonitis were reduced 26% and 41.5%, respectively, after 1 week of treatment,
      indicating the peritoneal production of nitric oxide during peritonitis. In the
      evolutional study, a 5.1-fold increase of peak nitrite levels in bacterial
      peritonitis (n = 13) and a 2.5-fold increase in fungal peritonitis (n = 3) were
      observed compared to controls. Nitrite gradually declined to control levels (9.3
      +/- 7.2 days) after effective antibiotic treatment, but took longer than to
      normalize leukocyte count in the peritoneal dialysate effluent (3.9 +/- 1.9
      days). In four patients with refractory peritonitis (Candida infection in three,
      Acinetobacter infection in one), the nitrite levels remained elevated 2-fold
      despite treatment, and the catheters were removed. It is concluded that nitrite
      levels in peritoneal dialysate effluent may serve as a marker to assess treatment
      efficacy in CAPD patients with peritonitis.

PMID- 9017625
TI  - Dialysis fluid cytotoxicity and inhibition of host defence in cultured human
      mesothelial cells are neutralized rapidly with incubation in the peritoneum.
AB  - BACKGROUND: A recent survey puts the global dialysis population at 535100; of
      those on peritoneal dialysis, 85% are on continuous ambulatory peritoneal
      dialysis. Current hyperosmolar dialysis fluids are toxic to peritoneal cells and
      inhibit certain host-defence functions. An alternative preparation, glucose
      polymer, has recently been developed. METHODS: Mesothelial cell viability,
      interleukin-6 and prostacyclin synthesis, after exposure to 7.5% glucose polymer,
      1.36% glucose or 3.86% glucose peritoneal dialysis effluent solution was
      assessed. RESULTS: In its neat form, at an original pH of 5.4, glucose polymer
      was as toxic as hyperosmolar solutions (P < 0.01). Synthesis of interleukin-6 and
      prostacyclin were significantly inhibited by neat dialysis fluid, (P < 0.01).
      However, after an in vivo intraperitoneal incubation of only 15 min the toxicity
      of all solutions tested in vitro was lost. CONCLUSIONS: Despite rapid in situ
      neutralization of dialysis fluid toxicity, mesothelial injury and inhibition of
      host-defence function, early in the dialysis cycle, may affect peritoneal
      physiology given the complex network of pathways to which these cells contribute.
      Although recent trials indicate improved ultrafiltration is achievable with
      glucose polymer, it is not a biocompatible dialysis fluid in its current
      manufactured form.

PMID- 9017626
TI  - Deposition of anti-actin antibodies in the kidney of a patient with systemic
      lupus erythematosus under immunosuppressive treatment.

PMID- 9017627
TI  - Membranoproliferative glomerulonephritis and haemolytic-uraemic syndrome in a
      patient with congenital chloride diarrhoea.

PMID- 9017628
TI  - Adult minimal change disease presenting with bilateral pulmonary artery
      thromboses--a reversible complication.

PMID- 9017629
TI  - Acute renal failure associated with carcinoid crisis.

PMID- 9017630
TI  - Hyponatraemic renal pseudofailure--don't forget the possibility of uroperitoneum.

PMID- 9017631
TI  - Perforation of the gall bladder in a patient on continuous ambulatory peritoneal
      dialysis.

PMID- 9017632
TI  - Successful long-term treatment of post-transplant erythrocytosis with losartan.

PMID- 9017633
TI  - The successful conversion to Tacrolimus (FK506) of a renal transplant recipient
      with cyclosporin-induced haemolytic-uraemic syndrome.

PMID- 9017634
TI  - Papillary necrosis in a ballet dancer with no history of analgesic abuse.

PMID- 9017635
TI  - Localization of ectopic parathyroid tissue: usefulness of 99mTc sestamibi
      scanning in a dialysis patient with severe secondary hyperparathyroidism.

PMID- 9017636
TI  - Renal artery stenting.

PMID- 9017637
TI  - How to evaluate hypercalcaemia in the patient with chronic renal failure.

PMID- 9017638
TI  - William Charles Wells (1757-1815)--a nephrologist of the Scottish enlightenment.

PMID- 9017639
TI  - No proof for a particular role of combination analgesics causing end-stage renal
      failure.

PMID- 9017640
TI  - Diagnostic value of bone marrow biopsy in patients with AA-type renal amyloidosis
      secondary to ankylosing spondylitis.

PMID- 9017641
TI  - Does torasemide reduce proteinuria in nephrotic patients?

PMID- 9017642
TI  - Severe acute renal failure after administration of contrast media in a patient
      treated with cisplatin.

PMID- 9017643
TI  - Correlation of whole blood activated partial thromboplastin time and plasma
      activated partial thromboplastin time in haemodialysis patients.

PMID- 9017644
TI  - Transcatheter intravascular embolotherapy of renal arteriovenous fistula--method
      of choice.

PMID- 9017645
TI  - Losartan in post-transplant erythrocytosis.

PMID- 9017660
TI  - Retinal protein kinase C.
AB  - The protein kinase C (PKC) family of serine/threonine kinase isoenzymes are
      universally expressed in vertebrate tissues where they control vital cellular
      functioning. PKC comprises twelve currently identified mammalian isoenzymes,
      described in three distinct groups according to their need for different effector
      stimulation. Immunological localisation studies in various vertebrate retinas
      have indicated the presence, so far, of eight of the PKC subspecies, each with a
      unique cellular distribution in this tissue. Use of these immunological probing
      techniques with antibodies raised to the individual PKC family members by
      immunohistochemistry and western blotting, along with biochemical tools such as
      the potent activators, the tumour-promoting phorbol esters can hopefully lead to
      elucidation of the roles of these enzymes in the neural retina. Research work to
      date has pinpointed a number of roles for PKC in this tissue including control of
      dopamine release, modulation of glutamate receptor function (probably by a
      process of direct receptor phosphorylation), phosphorylatory modulation of GABAC
      receptor function, an involvement in the retinal ischaemic cascade process (the
      relevance of which is unknown as yet), involvement in control of cytoskeletal
      interactions by cytoskeletal element-kinase action and feedback control of
      enzymes involved in the process of inositol phosphate signalling. PKC has been
      shown to have an important regulatory role in the process of phototransduction:
      many of the enzymes and proteins making up the phototransduction cascade act as
      in vitro and in vivo substrates for PKC-dependent phosphorylation and can have
      their normal function modified in this way. Also, PKC has been implicated in the
      control of spinule formation in the retina, a process involved in retinal
      synaptic plasticity and functioning. All of this work has been described, herein.
      Collation and utilisation of knowledge of all of the work described here may help
      us to determine the exact roles for individual isoenzymes in the retina. This in
      turn may help us to understand and further to prevent pathological conditions
      leading to inappropriate retinal functioning and possible blindness. Furthermore,
      understanding the roles of PKC in the neural retina may lead us to vital clues in
      the understanding of the functioning of this important group of enzymes in the
      nervous system as a whole and eventually to the prevention of many major
      neuropathological disorders.

PMID- 9017661
TI  - Ruthenium red as a tool to study calcium channels, neuronal death and the
      function of neural pathways.
AB  - The inorganic polycationic dye ruthenium red (RuR) exerts several effects on the
      nervous system when added in physiological solutions, both in vivo and in vitro.
      Part of these effects, including the paralysis observed in mammals after the
      systemic administration of RuR, can be accounted for by the binding of RuR to
      nerve ending membranes, which results in inhibition of Ca2+ influx through
      voltage-sensitive calcium channels and the consequent inhibition of
      neurotransmitter release. On the other hand, the administration of RuR into the
      cerebrospinal fluid induces intense convulsive activity, and its microinjection
      into the substantia nigra reticulata or the hippocampus leads to various motor
      behavior alterations that can be related to hyperexcitability of the neurons of
      the injected region. In addition, RuR penetrates the neuronal somata present in
      the area injected and induces cell destruction, which has been interpreted as an
      excitotoxic action of the dye. The penetration and the toxicity of RuR were also
      observed in primary neuronal cultures but did not occur in pure glial cultures,
      suggesting a selective action on neurons. In the present article the in vitro and
      in vivo effects of RuR are reviewed and discussed in terms of the usefulness of
      the dye as an interesting tool to study calcium channels linked to transmitter
      release, neuronal death mechanisms and the function of neural pathways.

PMID- 9017662
TI  - Further characterisation of [3H]8-hydroxy-2-(di-N-propylamino)tetralin binding
      sites in human brain postmortem.
AB  - The saturation parameters and the pharmacological characteristics of the binding
      of the serotonin 1A (5-HT1A) receptor agonist [3H]8-hydroxy-2-(di-N
      propylamino)tetralin ([3H]8-OH-DPAT), as well as the effects of nucleotides and
      divalent cations (Mg2+, Mn2+) on it, were compared in some human postmortem brain
      regions: the main cortical areas, hippocampus and striatum. [3H]8-OH-DPAT
      labelled a single population of recognition sites with the highest maximal
      capacity (Bmax) in the hippocampus and the lowest affinity in the striatum. Among
      the various cortical areas, the frontal cortex exhibited the highest Bmax. The
      pharmacological profile of the [3H]8-OH-DPAT binding sites was consistent with
      the labelling of the 5-HT1A receptor in the hippocampus and cortex, whereas the
      striatal site shared strong similarity to the presynaptic serotonin transporter.
      Modulation of [3H]8-OH-DPAT binding by divalent cations and nucleotides was
      detectable and stable in autopsy brains. In particular, nucleotide effects were
      area-dependent: guanosine thiotriphosphate (GTP gamma S) reduced [3H]8-OH-DPAT
      binding to the same extent in the hippocampus and frontal cortex, while having no
      effect in the striatum. Divalent cation effects depended also upon the brain
      area: in the striatum, they inhibited [3H]8-OH-DPAT binding, while stimulating it
      in the hippocampus and, with less extent, in the frontal cortex. In summary,
      these findings suggest that the [3H]8-OH-DPAT binding and its modulatory
      parameters in human brain tissues seem to show similarities but also some
      differences with respect to those determined in the rat brain. Furthermore,
      postmortem stability of GTP and divalent cation sensitive 5-HT1A receptors
      underlines the need for further studies on the regulatory and functional
      properties of this receptor in the human brain.

PMID- 9017663
TI  - Autoradiography of [3H]alpha,beta-methylene-ATP binding sites in medulla
      oblongata and spinal cord of the rat.
AB  - Excitatory purinoceptors of P2x-type have long been known to exist on smooth
      muscle cells, but recently it has been shown that they are also involved in
      synaptic transmission in the CNS. We have used a P2x-specific agonist, alpha,beta
      methylene-ATP, as a 3H-labelled radioligand, to study the distribution and
      characteristics of P2x receptor-binding sites in the spinal cord and medulla
      oblongata. Using auto-radiographic techniques, [3H]alpha,beta-methylene-ATP
      binding was found throughout the grey matter of the spinal cord with small areas
      of above-average density of binding sites in the marginal zone and substantia
      gelatinosa at all spinal levels and in the central grey matter of the thoracic
      spinal cord. In the medulla, [3H]alpha,beta-methylene-ATP binding was found to be
      strong in all cranial nerve nuclei, particularly those known to receive primary
      sensory fibres. We have found that the binding of [3H]alpha,beta-methylene-ATP in
      the spinal cord and medulla was inhibited by a broad-spectrum P2-receptor
      antagonist suramin (IC50 approximately 27 microM). This is in accordance with the
      data obtained previously in the forebrain and cerebellum. There was, however, no
      inhibition of [3H]alpha,beta-methylene-ATP binding by another close analogue of
      alpha,beta-methylene-ATP and P2x ligand beta,gamma-methylene-ATP (10 microM). The
      latter result is discussed in terms of possible involvement of Ca2+ in the
      binding of [3H]alpha,beta-methylene-ATP to P2x receptors in the CNS.

PMID- 9017664
TI  - Cholecystokinin-GABA interactions in rodent cortex: analyses of cholecystokinin
      effects on K(+)- and L-glutamate-induced release of [3H]GABA from rat cortical
      slices and cultured mouse cortical neurones.
AB  - Neurones of the cerebral cortex immunoreactive for the neuropeptide,
      cholecystokinin (CCK), also invariably contain GABA. Hence CCK is believed to
      modulate some aspect of GABAergic synaptic activity. The present study therefore
      investigated the effects of CCK on basal, K(+)- and L-glutamate-induced release
      of [3H]GABA from slices of rat neocortex and cultured murine neocortical
      neurones. Rat neocortical prisms loaded with [3H]GABA (10 nM) were superfused
      with Krebs-Henseleit buffer and stimulated twice (S1 and S2, 2 min) with K+ (30
      mM). Release associated with each stimulus was measured and expressed relative to
      basal release (R1 and R2). The effects of non-selective and CCKB selective
      agonists, CCK-8S and CCK-4, respectively, on basal and K(+)-induced release of
      [3H]GABA were subsequently assessed by alternately including the peptides in S2
      and comparing R2/R1 and S2/S1 ratios to control experiments. Contrary to previous
      findings, CCK-8S (30 nM-1 microM) and CCK-4 (0.3 nM-1 microM) failed to influence
      basal or K(+)-induced release. In similar experiments, murine cortical neurones
      superfused with HEPES balanced salt buffer, released exogenous [3H]GABA upon
      stimulation (1 min) with either K+ (55 mM) or L-glutamate (30 microM). However,
      CCK-8S, CCK-4 (both 300 nM-1 microM) and the CCKB selective antagonist, L365,260
      (1 microM), failed to influence basal, K(+)- or L-glutamate-induced release of
      [3H]GABA from these neurones when included in S2. These data therefore do not
      support the postulate that CCK acting via CCKA or CCKB receptors modulates
      release of GABA under the present experimental conditions. GABA-CCK interactions
      were not specifically studied because only L-glutamate (30 microM) significantly
      elevated release of CCK-like immunoreactivity (115% above basal) in murine
      cortical neurones: basal release of CCK was estimated to be 7 and 11 pM from
      neurones and slices, respectively. Further studies employing more rigorous
      stimulation and perhaps examining endogenous GABA release are necessary to fully
      investigate the co-release of CCK and GABA.

PMID- 9017665
TI  - Systemic administration of defined extracts from Withania somnifera (Indian
      Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic
      and GABAergic markers in rat brain.
AB  - Although some promising results have been achieved by acetylcholinesterase
      inhibitors, an effective therapeutic intervention in Alzheimer's disease still
      remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from
      aqueous methanol extract from the roots of cultivated varieties of Withania
      somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to
      blackish brown exudation from steep rocks of the Himalaya mountain, are used in
      Indian medicine to attenuate cerebral functional deficits, including amnesia, in
      geriatric patients. The present investigation was conducted to assess whether the
      memory-enhancing effects of plant extracts from Withania somnifera and Shilajit
      are owing to neurochemical alterations of specific transmitter systems.
      Therefore, histochemistry to analyse acetylcholinesterase activity as well as
      receptor autoradiography to detect cholinergic, glutamatergic and GABAergic
      receptor subtypes were performed in brain slices from adult male Wistar rats,
      injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X
      and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of
      40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced
      acetylcholinesterase staining, restricted to the basal forebrain nuclei including
      medial septum and the vertical limb of the diagonal band. Systemic application of
      the defined extract from Withania somnifera, however, led to differential effects
      on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was
      found in the lateral septum and globus pallidus, whereas in the vertical diagonal
      band AChE activity was reduced following treatment with sitoindosides VII-X and
      withaferin-A. These changes were accompanied by enhanced M1-muscarinic
      cholinergic receptor binding in lateral and medial septum as well as in frontal
      cortices, whereas the M2-muscarinic receptor binding sites were increased in a
      number of cortical regions including cingulate, frontal, piriform, parietal and
      retrosplenial cortex. Treatment with Shilajit or the defined extract from
      Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor
      NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical
      regions studied. The data suggest that Shilajit and the defined extract from
      Withania somnifera affect preferentially events in the cortical and basal
      forebrain cholinergic signal transduction cascade. The drug-induced increase in
      cortical muscarinic acetylcholine receptor capacity might partly explain the
      cognition-enhancing and memory-improving effects of extracts from Withania
      somnifera observed in animals and humans.

PMID- 9017666
TI  - Suppression of cholinergic activity via the dopamine D2 receptor in the rat
      striatum.
AB  - The effect of dopamine (DA) D2 receptor on extracellular choline (Ch) and
      acetylcholine (ACh) levels in rat caudate-putamen (striatum) was investigated by
      means of microdialysis. The systemic, intraperitoneal (i.p.), injection of (+/-)
      2-(N-phenylethyl-N-propyl) amino-5-hydroxytetralin (N-434), a specific DA D2
      receptor agonist decreased striatal ACh release in a dose-dependent manner and
      the i.p. injection of sulpiride, a specific DA D2 receptor antagonist, increased
      the ACh release in a dose-dependent manner. In contrast, extracellular Ch levels
      were increased by the agonist and decreased by the antagonist. An increased Ch
      uptake was observed in sulpiride-treated rats and a decreased Ch uptake was
      observed in N-434-treated rats. The effects of the D2 agonist on extracellular
      Ch, ACh and Ch uptake were completely antagonized by the D2 antagonist. These
      results suggest clearly an inhibition of ACh release by D2 receptor activation,
      contrasting with previous findings on DA-ACh interaction. The inverse
      relationship between extracellular Ch and ACh reflects a change in the Ch uptake
      owing to a change in cholinergic neuron activity via the D2 receptor mechanisms.

PMID- 9017667
TI  - Regional differences in NaCl-induced increase of the potency of bicuculline to
      displace [3H]muscimol binding.
AB  - It has been shown that the potency of bicuculline to displace [3H]muscimol
      binding to crude brain membranes can be enhanced markedly by different anions.
      This study shows that although bicuculline alone was a more potent displacer of
      [3H]muscimol binding in cortical than in cerebellar membranes, the NaCl (250 mM)
      induced leftward shift of the bicuculline inhibition curve of [3H]muscimol
      binding was considerably higher in cerebellum than in cortex. The some
      concentration of NaCl failed to affect either the affinity or the density of
      cortical and cerebellar [3H]muscimol binding sites. The results suggest that
      sodium chloride is able to reveal regional differences in bicuculline potency.

PMID- 9017668
TI  - Glutamate regulation of dopamine release in guinea pig striatal slices.
AB  - The effect of L-glutamic acid (L-Glu) on basal and electrically evoked [3H]
      dopamine efflux in guinea pig striatal slices was studied. In the presence of
      magnesium, L-Glu significantly increased spontaneous [3H]-dopamine efflux. This
      response was unaffected by the non-NMDA receptor antagonist, 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), the non-competitive NMDA receptor antagonist,
      D-5-methyl-10,11, dihydro-5-H-dibenzo-[a,d]-cyclohepten-5,10-imine maleate (MK
      801), the glycine antagonist 7-chlorokynurenic acid (7-CL-KYN) and by the
      metabotropic receptor antagonist (+)-alpha-methyl-4-carboxyphenyl-glycine (alpha
      M4CPG) and L-2-amino-3-phosphonopropionic acid (L-AP3). However, the metabotropic
      glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (t
      ACPD), increased spontaneous [3H]-dopamine efflux, as did L-Glu, and this
      response was completely counteracted by alpha-M4CPG. In the absence of magnesium,
      L-Glu induced a concentration-dependent increase in basal [3H]-dopamine efflux,
      which was prevented by MK-801. In electrically stimulated striatal slices L-Glu,
      applied 25 min before the stimulation, concentration-dependently increased the
      [3H]-dopamine efflux both in the presence and in the absence of magnesium. This
      effect was completely prevented by CNQX, but not by MK-801 or DL-2-amino-5
      phosphono-pentanoic acid (AP5). On the contrary, L-Glu, applied during electrical
      stimulation (2 min) in the absence of Mg2+, increased the [3H]-dopamine efflux to
      200%, and this effect was partly counteracted by MK-801. These results provide
      evidence that different subtypes of excitatory amino acid receptors modulate [3H]
      dopamine efflux depending on the functional state (rest or activity) of the nerve
      endings. The spontaneous [3H]-dopamine efflux appears to be controlled by
      metabotropic receptors in the presence of Mg2+ and by NMDA receptors in its
      absence. Conversely, the AMPA/kainate receptors facilitate the electrically
      evoked [3H]-dopamine efflux in the presence of Mg2+, whereas the NMDA receptors
      appeared to be operative, in the absence of Mg2+, as long as L-Glu was applied
      simultaneously with the electrical stimulation.

PMID- 9017669
TI  - Mechanism of adenosine accumulation in the hippocampal slice during energy
      deprivation.
AB  - The mechanism by which adenosine accumulates in the hippocampal slice during
      energy deprivation was investigated by examining the adenosine A1 receptor
      mediated depression of synaptically evoked field potentials in the CA1 area.
      Blocking of the mitochondrial electron transport chain with 200 microM sodium
      cyanide or mitochondrial uncoupling with 50 microM 2,4-dinitrophenol both
      produced a rapid depression of synaptic transmission that was antagonised by 1
      microM 8-cyclopentyl-1, 3-dimethylxanthine, an adenosine A1 receptor antagonist.
      Cellular ATPase inhibition or elevation of cytosolic phosphocreatine failed to
      alter the 2,4-dinitrophenol induced depression of synaptic transmission. Attempts
      to block mitochondrial ATP synthesis with 3 microM oligomycin or 75 microM
      atractyloside did not cause depression of synaptic transmission. 100 microM
      iodotubercidin, an adenosine kinase inhibitor, alone produced a depression of
      synaptic transmission that was completely reversed by 1 microM 8-cyclopentyl-1,3
      dimethylxanthine; however, a simultaneous or independent episode of hypoxia
      surmounted the adenosine A1 receptor antagonism and produced approximately 50%
      depression of synaptic transmission. Depression of synaptic transmission by
      hypoxia, cyanide or 2,4-dinitrophenol is a result of rapid adenosine accumulation
      and activation of extracellular adenosine A1 receptors. Although this early
      depression of synaptic transmission is a consequence of inhibition of normal
      mitochondrial function, it is not a result of depletion of cytosolic ATP, since
      attempts to preserve ATP did not maintain synaptic transmission during
      mitochondrial poisoning, and inhibitors of oxidative phosphorylation did not
      produce synaptic depression.

PMID- 9017671
TI  - The effect of quinolinate on rat brain lipid peroxidation is dependent on iron.
AB  - Quinolinate, an endogenous excitotoxic metabolite of tryptophan with affinity to
      the N-methyl-D-aspartate type of glutamate receptor, is known as a stimulator of
      lipid peroxidation in vitro [Neurochem. Res. (1991) 16, 1139-1143]. To analyse
      the mechanism of this quinolinate toxicity we used the thiobarbituric acid test
      to measure malondialdehyde in homogenates of rat cerebral hemispheres incubated
      in air at 37 degrees C for 30 min in the presence of 0.015-15.0 mM quinolinate,
      endogenous iron or 0.5-2.0 microM FeSO4 and with or without 250 microM ascorbate.
      Quinolinate in the concentrations of 0.15-2.5 mM stimulated lipid peroxidation in
      the homogenates in the presence of 0.5-2.0 microM Fe2+. However, quinolinate
      concentrations higher than 3.0 mM inhibited the lipid peroxidation at all the
      tested concentrations of iron. In the presence of a potent iron chelator (10
      microM deferoxamine) quinolinate completely failed to induce lipid peroxidation
      in rat brain homogenates. Spectral analysis revealed that quinolinate is able to
      form a complex with Fe2+. The results suggest that quinolinate does not have a
      direct peroxidative effect, but that it modulates lipid peroxidation via its
      interaction with iron.

PMID- 9017670
TI  - Bioactive lipids in excitatory neurotransmission and neuronal plasticity.
AB  - Long-term potentiation (LTP), a model of activity-dependent synaptic plasticity
      and of certain forms of memory, comprises the persistent enhancement of
      excitatory neurotransmission that results from high-frequency activation. A
      presynaptic component of LTP is thought to be modulated by a retrograde messenger
      generated by the postsynaptic neuron. Arachidonic acid, nitric oxide, carbon
      monoxide and PAF have each been proposed as retrograde messengers in LTP, but
      arachidonic acid, unlike PAF, requires NMDA receptor activation. A PAF antagonist
      (BN 52021) that provides neuroprotection in ischemia-reperfusion displaces [3H]
      PAF bound to presynaptic membranes, blocks PAF-induced glutamate exocytosis and
      inhibits LTP. An antagonist selective for the intracellular PAF binding site (BN
      50730) did not affect LTP, nor did BN 52021 modify NMDA currents. LTP was induced
      with weak synaptic stimulation coupled with postsynaptically administered enzyme
      resistant mcPAF. Theta-burst stimulation (10 min) after bath applications of
      mcPAF (1 microM) induced APV-independent LTP that was blocked by 5 microM BN
      52021. When this antagonist was infused into the hippocampus before or
      immediately after training, it impaired memory of inhibitory avoidance training
      in the rat. Memory was not altered if the antagonist is infused 30 or 60 min
      after training. Moreover, mcPAF enhances memory on retention test performance of
      step-down inhibitory avoidance habituation and learning in rats. Also, memory was
      studied using a caudate nucleus-dependent cued water maze task. Rats received an
      8 trial (30 s intertrial interval) training session in which a visible cued
      escape platform was located in a different quadrant of the maze of each trial.
      Following trial 8, the rats received a unilateral post-training intra-caudate
      injection of mcPAF (1 microgram/0.5 microliter), BN 52021 (0.5 microgram/0.5
      microliter) or vehicle. On a retention test session 24 h later, latency to mount
      the escape platform was used as a measure of memory. The retention test escape
      latencies of rats given mcPAF were significantly lower than those of the vehicle
      injected controls, indicating a memory enhancing effect of mcPAF. Injection of
      mcPAF did not affect retention when administered 2 h post-training, indicating a
      time-dependent effect of mcPAF on memory. The latencies for animals injected with
      BN 52021 were significantly higher than those of the controls, indicating that
      antagonism of endogenous PAF impairs memory. The findings show that PAF plays a
      role in memory formation in a caudate-mediated cued discrimination task.
      Administration of BN 52021 2 h post-training had no affect on retention,
      indicating a time-dependent effect of endogenous PAF on memory formation. PAF,
      the most potent bioactive lipid known, modulates excitatory synaptic
      transmission, neuronal plasticity and memory. When PAF production is
      overstimulated as in seizures or ischemia, it becomes neurotoxic.

PMID- 9017672
TI  - Ethics: the new mainstream issue for the ICU and SCCM.

PMID- 9017673
TI  - Physician virtues and communicating with patients.
AB  - The growth of profit-driven medicine and managed care as well as the increasingly
      technologic focus of Western medicine have stimulated much reflection on the
      fundamental values of the medical profession and on the meaning of being a "good
      doctor." Many patients and many in the medical community have grown concerned
      about the fate of the doctor-patient relationship. In practicing medicine,
      physicians must be guided both by the basic principles of biomedical ethics and
      by Beauchamp's and Childress's four fundamental virtues: compassion,
      trustworthiness, discernment, and moral integrity. In addition, physicians must
      make the commitment to develop strong communication skills, for it is through
      communicating with patients that we forge a relationship with them and make them
      feel cared for. Good communication skills not only improve patient satisfaction
      and facilitate resolving the difficult ethical problems that arise in critical
      care but have also been shown to improve certain health outcomes. Unfortunately,
      studies have repeatedly shown physicians to have poor communication skills. In
      this article we identify key elements in preserving medicine's "covenant of
      trust" and in establishing good communication and rapport in critical care
      settings. We identify specific obstacles to good communication and propose
      strategies for overcoming them.

PMID- 9017674
TI  - Health professional decision-making in the ICU: a review of the evidence.
AB  - End-of-life decisions in the ICU are often complex and emotionally charged.
      Intensivists can correct the physiologic abnormalities of acute and chronic
      illness with drugs and technology, and prolong life in many situations.
      Understanding and attending to the psychological and emotional needs of not only
      patients but also their families are part of the delivery of compassionate
      critical care. The process of communicating and decision-making on the ICU team
      and in family units has been a domain of active research over the past decade.
      Studies on do-not-resuscitate orders, and advanced and delayed directives
      comprise a portion of this work. This article contains a brief summary of
      selected research evidence on these difficult end-of-life issues.

PMID- 9017675
TI  - Environments that support ethical practice.
AB  - Our healthcare system is fundamentally flawed in the ability to provide quality
      end-of-life care. The provision of quality end-of-life care involves a complex
      interaction of personal, professional, and societal values and practices.
      Attention to each dimension of end-of-life care is essential to improve the care
      of the dying patient and his/her family. Given the complexity of this problem,
      this article focuses on the critical care environment and the aspect of
      organizational culture and specific strategies for improvement. Several inter
      related components of an environment which may foster ethical thinking, decision
      making, and behaviors are discussed including organizational culture, individual
      agency, collaboration, and educational resources. Every member of the healthcare
      team has the responsibility to be a catalyst for creating a critical care
      environment where ethical practice is expected and rewarded rather than punished
      and suppressed. As a healthcare team, our ultimate goal is to provide healing and
      humane end-of-life care for all patients and families.

PMID- 9017676
TI  - Withholding and withdrawal of life support: ethical, legal, and clinical aspects.
AB  - The withholding and withdrawal of life support are processes by which various
      medical interventions either are not given to or are taken away from patients,
      with the expectation that they will die as a result. The propriety of withholding
      and withdrawal of life support has been supported by ethical statements from
      groups such as the Task Force on Ethics of the Society of Critical Care Medicine,
      and by a series of legal decisions beginning with the Quinlan case. Surveys of
      healthcare professionals indicate that most ICU physicians withhold and withdraw
      life support on a regular basis, that they consider these processes ethically
      equivalent, that they recommend withholding and withdrawal of life support based
      upon prognosis (which may be expressed as futility), and that they consider
      patient and surrogate wishes to be most important in deciding to forego life
      sustaining treatment, but place these wishes in the context of their own
      assessment of prognosis. Observational studies show that: withholding and
      withdrawal of life support occur frequently, the frequency has increased over the
      past several years in some ICUs, patients and families generally agree with
      physician recommendations to limit care or request such limitation, disagreements
      sometimes occur on this issue, withdrawal of life support occurs more commonly
      than withholding of life support in most ICUs, cardiopulmonary resuscitation is
      the therapy most frequently withheld, mechanical ventilation is the therapy most
      frequently withdrawn, this withdrawal process usually is gradual, and it usually
      is facilitated by the administration of sedatives and analgesics. Clinical
      information such as this is helping to define a standard of care in the area of
      withholding and withdrawal of life support.

PMID- 9017677
TI  - Ethics of allocating intensive care unit resources.
AB  - ICU clinicians commonly make decisions that allocate resources. Because of the
      high cost of ICU care, these practitioners can expect to be involved in the
      growing dilemma of trying to meet increasing demand for healthcare services
      within financial constraints. In order to participate meaningfully in a societal
      discussion over fairness in allocating scare and expensive resources, ICU
      practitioners should have more than a superficial knowledge of the principles of
      distributive justice. Distributive justice refers to fairness in the distribution
      of limited resources and benefits. Fairness refers to giving equal treatment to
      all those who are the same with regard to certain morally significant
      characteristics and treating in a different manner those who are not the same.
      Although theoretical issues remain unresolved as to which characteristics should
      be most significant, the United States has a strong cultural value that regards
      individuals as inherently valuable and having equal social worth. From this, it
      is likely that only an egalitarian approach to allocation of lifesaving
      healthcare resources will be acceptable. Studies of how ICU resources have been
      allocated during times of scarcity indicates that, in general, when beds are
      scarce, the average severity of illness of those admitted to the ICU increases.
      However, in some hospitals, political and economic factors appear to play
      important roles in determining who has access to scarce ICU beds. Of great
      concern is documentation of a widespread pattern in which fewer hospital
      resources, including ICU resources, are provided to seriously ill patients of
      minority status or with low levels of insurance reimbursement. How society's
      values get translated into allocation decisions is another unresolved issue. One
      recent example of how this occurred is the Oregon Medicaid Plan. This plan
      extended Medicaid coverage to additional people in poverty, despite the same
      amount of state and federal funds. This was accomplished by not reimbursing what
      were regarded as marginally beneficial services on the basis of medical and
      community input. Portents of how society might be involved in the future of
      health care are illustrated by the argument that society should limit access to
      all therapies except palliative care solely on the basis of advanced age. Until
      an open consensus develops in U.S. society about how to allocate scarce
      healthcare resources, the delivery of ICU care will continue to be at risk of
      covert, de facto rationing based on ability to pay, race, or other nonmedical
      personal characteristics.

PMID- 9017678
TI  - Economic implications of the timing of do-not-resuscitate orders for ICU
      patients.
AB  - Healthcare reform continues to move forward, with the influence of managed care
      increasing in most areas of the United States. Strategies for cost containment
      are being considered to limit marginally beneficial health care, including futile
      care policies, capitation, preset limits on health care, and guidelines for
      writing do-not-resuscitate (DNR) orders. Recent studies which attempted to
      improve communication between patients and physicians have failed to improve the
      quality of end-of-life care offered by healthcare providers. In other recent
      works, the timing of when DNR orders are written has been associated with
      shortening needed hospital and ICU care, as well as effecting significant
      reductions in resources utilized. This study reviews the current literature with
      respect to the timing of when DNR orders are written. We present a conservative
      estimate that for each ICU patient moved from late DNR to early DNR status,
      approximately $10,000 per patient could be saved. Moreover, approximately 0.5% of
      all ICU care could be limited should DNR orders be written earlier in a patient's
      hospital or ICU stay. In addition, a shift from open-format ICUs to semiclosed
      units managed by qualified critical care physician directors would reduce the
      number of patients with futile or failed cardiopulmonary resuscitation, and
      increase the number of patients having care withheld or withdrawn after failed
      ICU therapy. Such a change would result in more substantial savings.

PMID- 9017679
TI  - Prognoses of seriously ill hospitalized patients on the days before death:
      implications for patient care and public policy.
AB  - Troubling aspects of the experiences of patients at the ends of their lives have
      fueled interest in special benefits or privileges for this group. There is a
      presumption that being "at the end of life" is discernible. This study examines
      this presumption using data from two previously collected databases: the Study to
      Understand Prognoses and Preferences for Outcomes and Risks of Treatments
      (SUPPORT) and the Acute Physiology and Chronic Health Evaluation III (APACHE
      III). Both studies generated multivariable estimates of survival prognosis for
      hospitalized patients. SUPPORT included 9,105 patients with one of nine serious
      illnesses in five hospitals over 4 yrs, of whom 2,360 died in the hospital and
      4,537 died within 180 days of entry into the study. The APACHE III database
      describes 2,750 deaths in 16,622 ICU patients in 40 hospitals. The relationship
      of median estimates with time to death were examined for each source of data, for
      different diseases, and for ICU settings of care. In SUPPORT, the median
      predicted chance of survival for 2 months on the day before actual death was .17
      (interquartile range, .02-.40) and was .51 (.31-.66) 1 wk before death. Median
      prognoses varied substantially among diseases: the median for congestive heart
      failure patients was a .62 chance of living 2 months on the day before death,
      while lung cancer had only a .17 chance and coma patients only an .11 chance.
      Median prognostication estimates were not much different when given by physicians
      and were only a little more pessimistic in APACHE (median estimate for hospital
      survival on the day before death was .14 and 7 days before was .45). To make
      plans about care and to optimally support most dying persons and families,
      conversations must occur while the patient still has a considerable chance of
      surviving the current episode of illness. Using statistical estimates of
      prognosis to designate a category of "terminally ill" patients for public policy
      purposes is unavoidably arbitrary, will often be contested, and will have
      differential effects upon those dying with differing diseases.

PMID- 9017680
TI  - Resolving conflicts surrounding end-of-life care.
AB  - Critical care physicians are frequently called on to negotiate issues of medical
      management with patients, their families, and other physicians. These decisions
      frequently revolve around end-of-life care. Recent data suggest that such
      discussions are manageable. In one study, 57% of patients and surrogates agreed
      immediately to a physician's recommendation to limit intensive care and 90%
      agreed within 5 days, while multiple treating physicians came to consensus about
      such limits within 4 days in 92% of cases. If conflicts are rare, they are
      strongly felt. They arise when any one of the parties to a decision insists on
      continued care against the considered judgment of another. Since the alternative
      to aggressive ICU care is usually the death of the patient, it seems difficult to
      reconcile a physician's refusal to treat with patient autonomy. The concept of a
      fiduciary offers a model of the physician-patient relationship in which the
      physician commits himself to the patient's best interests but retains a role in
      defining those interests. This model offers significant benefits over medical
      futility in negotiating conflicts over end-of-life care.

PMID- 9017681
TI  - Ethical controversies in pediatric critical care.
AB  - Ethical dilemmas in clinical practice frequently center around who should make
      decisions for the patient, and what common principles can be used in making those
      decisions. In pediatrics, these dilemmas are complicated by balancing the
      interests of the child with the rights of parents and the responsibilities of
      clinicians. Other sources of controversy in caring for the pediatric population
      concern the confusion that continues around such issues as informed assent, the
      present standing of the "Baby Doe" regulations, and the forgoing of life
      sustaining treatments. This article discusses the framework for decision-making
      in children that has evolved in ethics and the law over the last several decades.

PMID- 9017682
TI  - The ethics of providing intensive care in managed care organizations.
AB  - To provide adequate and equitable care of critically ill patients, managed care
      organizations need to dedicate a reasoned proportion of organizational resources
      to the provision of critical care, distribute these resources fairly, establish
      appeal mechanisms, and monitor the outcomes of critical care. As in any
      healthcare delivery system with limited resources, it is inevitable that there
      will be limits to highly technological and costly life-sustaining care. Patients,
      physicians, and plan administrators will need to collaborate to decide priorities
      for care, since difficult trade-offs will need to be made between types of care
      and between quality and cost of care. The use of life-sustaining treatments
      should be informed by patient preferences and guided by many of the established
      guidelines for the provision of critical care. Physicians who provide critical
      care in a managed care organization should provide the most skilled and
      compassionate care to critically ill patients within the constraints of the
      ethically acceptable guidelines.

PMID- 9017683
TI  - [Gastroduodenal bicarbonate secretion: pharmacological modulation and
      contribution to mucosal protection].
AB  - Bicarbonate secretion from the surface epithelial cells of the gastroduodenal
      mucosa is an active process depending upon the tissue metabolism and plays an
      important role as the first line of defense in mucosal protection in
      collaboration with the mucus gel. This secretion is regulated by humoral and
      neural factors as well as endogenous prostaglandins (PGs) and is considered to be
      intracellularly mediated by cyclic AMP in the duodenum and by cyclic GMP in the
      stomach. Ca2 also acts as an intracellular mediator in this process. This
      bicarbonate secretion is markedly increased in response to luminal acid, mediated
      by PGs and neural factors including capsaicin-sensitive sensory nerves, and the
      impairment of this response is involved in the pathogenesis of various duodenal
      ulcer models induced by cysteamine, nonsteroidal antiinflammatory drugs and
      stress. The mechanisms underlying the mucosal protection by HCO3 secretion is two
      fold; One is the direct neutralization of H + in the lumen, and the other is the
      establishment of a pH gradient across the mucus gel aided by the physico-chemical
      property of the mucus. However, the cellular mechanisms of HCO3 secretion,
      including the receptors, the mediators and the signal transduction pathway have
      been poorly understood. The establishment of a method for preparing isolated
      epithelial cells and the probe for HCO3 secretion in isolated cells is required
      to further elucidate the mechanism of HCO3 secretion.

PMID- 9017684
TI  - [Measurement of reactive oxygen species in a biological system and its
      perspectives].
AB  - In recent years, reactive oxygen species have been implicated in the pathogenesis
      of a wide variety of disorders. Although the existence of reactive oxygen
      intermediates in drug metabolism can be inferred from end product analysis or
      from the effects of antioxidants or enzymes such as superoxide dismutase, only
      the technique of electron spin resonance (ESR) allows the direct detection of
      these highly reactive species. However, some free radical species cannot be
      detected by ESR due to their extremely short half-lives, which result in low
      steady-state concentrations of the radicals or to short radical relaxation times,
      which lead to a very broad line. These facts made recent development of spin
      trapping and chemiluminescence techniques are widely used to detect free
      radicals. The goal of this paper is to introduce the various assays available for
      measurement of reactive oxygen species in biological models. This paper will
      focus on two topics: (1) the spin-trapping/ESR technique in vitro and vivo and
      (2) the chemiluminescence-optical biosensor application of this technique, a very
      sensitive method that has the advantage of being able to provide continuous,
      online, nondestructive monitoring of reactive oxygen species.

PMID- 9017685
TI  - [Effects of efonidipine hydrochloride, a calcium antagonist derived from
      dihydropyridine, on acute myocardial ischemia in anesthetized open-chest dogs].
AB  - Effects of efonidipine hydrochloride (NZ-105), a dihydropyridine calcium
      antagonist, on the cardiovascular system were studied in dogs, in which the left
      anterior descending coronary artery (LAD) was ligated for 50 min. NZ-105 (10 or
      30 micrograms/kg), nifedipine (NIF, 1 or 3 micrograms/kg) or nisoldipine (NIS, 1
      or 3 micrograms/kg) was injected i.v. before LAD ligation. NZ-105, NIS or NIF
      decreased the total peripheral resistance (TPR) and blood pressure (BP) and
      increased the cardiac output (CO) and regional myocardial blood flow (RBF) dose
      dependently. LAD ligation decreased RBF and produced segmental bulging in the
      ischemic area, decreased BP and CO, and did not change TPR. NZ-105, NIF or NIS
      attenuated the LAD ligation-induced regional myocardial changes. During LAD
      ligation, in the presence of NZ-105 (30 micrograms/kg), the values of heart rate
      (HR), BP, and TPR were lower, and that of CO was higher than those in the absence
      of the drug. Similar results were obtained with NIS (3 micrograms/kg) except that
      the value of HR in the presence of NIS was not lower. During ischemia, the
      presence of NIF (3 micrograms/kg), did not significantly change the values of the
      systemic circulation from those observed in the absence of NIF. In conclusion, NZ
      105 may exert a cardioprotective effect by decreasing the oxygen demand of the
      ischemic heart.

PMID- 9017686
TI  - [Effects of lansoprazole on indomethacin-induced gastric bleeding and mucosal
      lesions in rats].
AB  - The effects of lansoprazole given intravenously on indomethacin-induced gastric
      bleeding and mucosal lesions were investigated in rats in comparison with those
      of omeprazole, famotidine and ranitidine. Lansoprazole inhibited gastric bleeding
      induced by indomethacin with an ID50 value of 0.29 mg/kg. Omeprazole and
      famotidine significantly inhibited gastric bleeding, but ranitidine provided
      negligible inhibition. A correlation was found between the inhibitory action of
      lansoprazole on gastric bleeding, and acid secretion, and its inhibitory action
      on gastric bleeding was almost completely abolished by adding 50 mM-HCl to the
      gastric perfusate, suggesting that lansoprazole's inhibitory action on gastric
      bleeding was mainly due to its antisecretory action. Lansoprazole inhibited the
      development of gastric lesions induced by indomethacin with an ID50 value of 0.10
      mg/kg, whereas histamine H2-receptor antagonists did not display a potent
      inhibitory effect. ID50 values for omeprazole, famotidine and ranitidine were
      0.69, 2.58 and 24.6 mg/kg, respectively. These results indicate that lansoprazole
      has a potent inhibitory action on indomethacin-induced gastric bleeding and
      mucosal lesions and that it is useful in the treatment of acute gastric mucosal
      lesions.

PMID- 9017687
TI  - [Effects of intravenous lansoprazole on acute gastric mucosal lesions and acid
      secretion].
AB  - The effects of lansoprazole given intravenously on gastric mucosal lesions,
      gastric bleeding and acid secretion were investigated in rats in comparison with
      those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited the
      formation of gastric mucosal lesions in rats induced by water-immersion stress or
      aspirin with ID50 values of 0.26 and 0.99 mg/kg, respectively, and also inhibited
      gastric bleeding induced by hemorrhagic shock or water-immersion stress with ID50
      values of 0.46 and 1.22 mg/kg, respectively. Lansoprazole was more potent than
      omeprazole, famotidine and ranitidine in inhibiting gastric mucosal lesions and
      hemorrhagic shock- or stress-induced bleeding. Famotidine and ranitidine showed
      negligible inhibition of water-immersion stress-induced gastric bleeding.
      Lansoprazole strongly inhibited water-immersion stress-stimulated acid secretion
      in rats, whereas famotidine and ranitidine did not show a potent inhibitory
      effect. These results indicate that lansoprazole exerts prominent inhibitory
      actions against the formation of gastric mucosal lesions and gastric bleeding by
      inhibiting acid secretion, and they show that it is superior to histamine H2
      receptor antagonists in inhibiting stress-induced gastric bleeding.

PMID- 9017719
TI  - The onset of upright locomotion and night wakings.

PMID- 9017718
TI  - Feelings of past lives as expected perturbations within the neurocognitive
      processes that generate the sense of self: contributions from limbic lability and
      vectorial hemisphericity.
AB  - Normal, young men and women who believed they may have lived a previous life (n =
      21) or who did not endorse (n = 52) this belief of "reincarnation" were exposed
      to partial sensory deprivation and received transcerebral stimulation by burst
      firing magnetic fields over either the left or right hemisphere. Individuals who
      reported belief in reincarnation could be discriminated from nonbelievers by
      their more frequent report of experiences of tingling sensations, spinning,
      detachment of consciousness from the body, and intrusions of thoughts that were
      not attributed to the sense of self. The results support the hypothesis that
      there may be neurocognitive processes which identify experiences as originating
      from the sense of self (episodic or autobiographical memory) or "not self." When
      anomalous experiences are beyond the boundary of the experiences contained with
      the generalization gradient of concurrent autobiographical memory, they are more
      likely to be attributed to culturally available default explanations such as
      living a previous life.

PMID- 9017720
TI  - Stimulus alignment and age in the selection of bigger rectangles.
AB  - 90 children (28 3-yr.-olds, 32 5-yr.-olds, and 30 8-yr.-olds) were presented
      pairs of quadrangles with the bases or the centers aligned and asked to select
      the bigger ones. 3- and 8-yr.-olds selected larger ones under both aligned
      conditions, while 5-yr.-olds selected the taller ones more often under the base-
      than under the center-aligned conditions. 5-yr.-olds selected the larger ones
      less often than 3- and 8-yr.-olds under the base-aligned condition. These results
      were discussed in relation to the attention given to height.

PMID- 9017721
TI  - Report form for aggressive episodes: preliminary report.
AB  - This paper gives a description of the development and initial empirical testing
      of the Report Form for Aggressive Episodes, a behavioural rating scale used to
      measure displayed aggressive behaviour and the situational determinant(s)
      according to a list of 30 potential precipitants to aggression. Findings from a
      one-year study in a special secure unit for the long-term treatment of dangerous
      patients show very high rates of underreporting of aggressive episodes in ward
      journals and patient files compared to this scale. Illustrations of the clinical
      use of the scale are provided by scoring examples and two case vignettes.

PMID- 9017722
TI  - Correlations between mood scores and volleyball performance.
AB  - Scores on the Profile of Mood States Inventory of 15 volleyball players at a
      small southwestern university were compared by means of regression analysis to
      the players' final season statistics. The analysis showed that Vigor as measured
      was related to several volleyball statistics.

PMID- 9017723
TI  - Nature of age-related changes in muscle strength of the extremities of women.
AB  - Age-related changes in the muscle strength of the extremities of 123 women (20-79
      years) were measured using a hand-held dynamometer. The isometric strength of
      three upper- and three lower-extremity muscle actions declined across ages. The
      magnitudes of strength decreases were a function of both the action and side
      tested. The earlier and steeper strength declines in actions of functional
      importance, e.g., knee extension, should alert those working with aging women of
      the potential importance of strengthening such muscle actions.

PMID- 9017724
TI  - Performance on the Purdue pegboard and finger tapping by schizophrenics after
      mellow and frenetic antecedent music.
AB  - Effects of musical selections on motor performance have been inconsistent. Using
      a 3-factor within-subjects design [mellow music (4:4 time), frenetic music (2:8
      time), and white noise conditions], each of 34 schizophrenic inpatients
      volunteered to perform the Purdue Pegboard and Finger Oscillation (Tapping)
      following 1-min. counterbalanced presentations of three types of music. Both
      pegboard and tapping performance were higher after frenetic music but unaffected
      by mellow music.

PMID- 9017725
TI  - Effects on contingent negative variation of set created by anticipating variable
      foreperiods.
AB  - The influence of set on a simple reaction time task was examined by comparing the
      differences of psychological factors between a group of subjects who expected and
      experienced a fixed foreperiod Control condition: 12 subjects) and another group
      of subjects who were instructed to expect variable foreperiods but experienced
      the same fixed foreperiod (Instruction condition: 11 subjects), using the index
      of contingent negative variation (CNV). The foreperiod of simple reaction time
      task in each condition was fixed at 3 sec. Subjects were required to respond to 2
      blocks of 24 trials, and each instruction was presented between blocks. On the
      second block CNV amplitudes were higher in the instruction condition as was every
      CNV component (early late, and whole component). The set created by anticipating
      variable foreperiods seems to increase cerebral activity, arousal, and attention
      during simple reaction time tasks.

PMID- 9017726
TI  - American Indian suicide and homicide rates and unemployment.

PMID- 9017728
TI  - Height, gross domestic product and suicide and homicide.

PMID- 9017727
TI  - Auditory temporal resolution in specifically language-impaired and age-matched
      children.
AB  - Recently there has been renewed interest in the auditory processing capabilities
      of children with specific language impairment. In this study, eight children with
      specific language impairment and eight nonimpaired, age-matched peers completed a
      task to assess temporal resolution abilities. Children were asked to detect a
      tone in three masking conditions wherein the masker contained silent gaps of 0
      msec., 40 msec., or 64 msec. in duration. Thresholds were measured in each
      masking condition at 500 Hz and 2000 Hz. Across the groups, thresholds decreased
      (improved) significantly as a function of increases in the duration of the gaps.
      Children in the two groups exhibited remarkably similar thresholds for the three
      masking conditions. However, children with specific language impairment required
      a significantly greater number of ascending trials to achieve the threshold
      criterion than did age-matched children. Results suggest that language-impaired
      children perceive temporal aspects of acoustic stimuli as well as their normally
      developing peers. Attentional mechanisms may play an important role in the
      difficulties they exhibit in auditory processing.

PMID- 9017729
TI  - Communication skill and behaviour disorder.
AB  - The aim was to identify changes in communication skills and behaviour disorder of
      15 clients with learning difficulties 6 mo. and 1 yr. after they moved from large
      to small-scale accommodations. Clients were allocated into a group of 6 with
      profound multiple learning difficulties, a preverbal group of 5, and a verbal
      group of 4. Communication skills were measured using the Preverbal Communication
      Schedule, and behavioural disorder was measured using the Aberrant Behaviour
      Checklist. Analysis showed that from the baseline to one year follow-up, there
      was a significant increase from baseline in social withdrawal by the clients with
      multiple difficulties but that there were improvements in communication skills of
      both preverbal and verbal clients. No control group was involved.

PMID- 9017730
TI  - Review of recent Chinese research on field dependence-independence in high-level
      athletes.
AB  - A review of seven studies in China concerning field dependence-independence among
      500 athletes in 10 different sports is presented. Athletes participating in
      closed-skill sports were more field-independent than those in open-skill sports.
      In closed-skill sports, high-level athletes were more field-independent than
      those of medium level. In open-skill sports involving direct contact, high-level
      athletes were more field-dependent than those of medium level. No significant
      relationship was found between field dependence-independence and athletes'
      performance in open skill sports in which no direct contact was involved.

PMID- 9017731
TI  - Social correlates of suicide in the British Isles.

PMID- 9017732
TI  - Aboriginal suicide in British Columbia.

PMID- 9017733
TI  - Effects of competitive activation on precision movement control.
AB  - Models of emotional activity consider that the emotional state can have general
      effects on movement control. This control depends on programmed movement
      invariants (movement sequence, duration of the relative phases, etc.) and on the
      setting of the movement parameters (amplitude, velocity, etc.). This study of 14
      adults shows an influence of the emotional state upon movement kinematics,
      namely, the peak velocity and the peak acceleration, the amplitude, and the
      duration of the acceleration phase.

PMID- 9017734
TI  - An explanation for inconsistency between psychophysical functions derived from
      different scaling methods on a prothetic continuum.
AB  - In this note is proposed an hypothetical explanation for the question of why, on
      a prothetic continuum, a psychophysical function obtained by direct scaling is
      inconsistent with that obtained by indirect scaling. We explain by making the
      assumption that there are two stages of sensory processes which transform a given
      stimulus value to a perceived value serially by logarithmic and exponential
      functions. It is illustrated that, on a prothetic continuum, a logarithmic
      function should be obtained by direct scaling and a power function should be
      obtained by indirect scaling if our assumption is expanded mathematically.

PMID- 9017735
TI  - Differences in psychomotor reaction time in male monozygotic twins discordant for
      lifetime cigarette smoking.
AB  - The effects of long-term cigarette smoking on psychomotor reaction time were
      investigated among 8 pairs of monozygotic male twins highly discordant for
      lifetime smoking (means 32.4 versus 0.6 pack-years). The men had no diagnosed
      cardiovascular disease or other major diseases, musculoskeletal complaints, or
      vision problems that might interfere with reaction time testing. The twins had
      similar education, work, and exercise histories; alcohol and coffee consumption
      and exposure to solvents were examined as possible confounds. Direct comparison
      of cotwins also controlled for age, genetics, and possible early environmental
      factors. Simple and choice reaction time were measured in the dominant hand and
      in both feet. The decision-time component of total reaction time was of primary
      interest. On average, long-term smokers had slower decision times than their
      nonsmoking twins; however, the differences were small (5 to 14%) and were not
      statistically significant for four of the six decision-time measures, perhaps due
      to the lack of power with only eight twin pairs. Further study may confirm our
      evidence suggesting that long-term cigarette smoking impedes reaction time, a key
      measure of function of the central nervous system.

PMID- 9017736
TI  - Teenagers' knowledge about prenatal exposure to cocaine.
AB  - The current study indicated limited knowledge among 124 teenagers about prenatal
      exposure to cocaine. Given the widespread problem of substance abuse among
      teenagers as well as high incidence of teenage pregnancies, there is a need to
      make this information more readily available.

PMID- 9017737
TI  - Odors as cues for the recall of words unrelated to odor.
AB  - The effectiveness of an ambient odor as a retrieval cue for words unrelated to
      odor was investigated. After incidental learning of 40 adjectives, 40
      participants were tested for recall during three unannounced recall phases (15
      min., 48 hr., and 5 days). Participants in two control conditions learned with no
      odor present and either had no odor present during any recall phase or only
      during recall after 5 days. Participants in two conditions learned with an odor
      present and either had the odor present during recall only after 5 days or during
      recall both after 15 min. and after 5 days. Analyses indicated that, while
      participants in the control conditions recalled significantly less during each
      succeeding recall phase, recall by participants in the two experimental
      conditions did not decrease significantly. Recall by participants in the two
      experimental conditions was significantly higher during recall after 5 days (when
      the odor was reintroduced) than either control group. The addition of a salient
      cue during learning and retrieval facilitated recall more than the presence of
      constant environmental cues.

PMID- 9017738
TI  - The method of subliminal psychodynamic activation: do individual thresholds make
      a difference?
AB  - The present experiment investigated the effects of subliminal psychodynamic
      stimuli on anxiety as measured by heart rate. Following an anxiety-inducing task,
      male and female subjects were tachistoscopically shown, at their subjective
      thresholds, one of five subliminal stimuli, MOMMY AND I ARE ONE, DADDY AND I ARE
      ONE (symbiotic messages). MOMMY HAS LEFT ME (abandonment message), I AM HAPPY AND
      CALM (positively toned but nonsymbiotic phrase), or MYMMO NAD I REA ENO (control
      stimulus). It was hypothesized that men would exhibit a greater decrease in heart
      rate after exposure to the MOMMY stimulus than the control message. No definitive
      predictions were made for women. The abandonment phrase was expected to increase
      heart rate. A positively toned message was included to assess whether its effects
      would be comparable to those hypothesized for the MOMMY message. The results
      yielded no significant effects for stimulus or gender and so provided no support
      for the hypotheses.

PMID- 9017739
TI  - Metric aspects of mental images.
AB  - This research concerns the representation of size and shape in long-term memory
      at different levels of abstraction. Some authors suggested a distinction between
      surface characteristics, including size, depending on an observer's point of view
      (viewer-centered), and abstract characteristic based only on an object's shape
      (object-centered). These studies raise the question of whether size-information
      is stored in long-term memory. This question may be dealt with by considering the
      topic of cognitive costs; since abstract representation needs more processing,
      more time is required to store fewer abstract representations than many viewer
      level representations. Two hypotheses were put forward: information about size is
      preserved when an intermediate time is allowed to process visual stimuli, whereas
      it is discarded when a longer time is available; subjects who have longer time
      focus on shape, while subjects who have less time do not. Subjects were assigned
      to two groups differing in the time allowed to learn visual images. Both groups
      had to recognize previously learned visual mental images. These images were built
      up by a subtraction task. The testing stimuli were identical to learned ones, of
      a different size, or of a different shape. Analysis showed that information about
      size is not held in long-term memory. As regards shape, results were
      controversial.

PMID- 9017740
TI  - Capacity for imagery and creative self-perceptions.
AB  - The influence of capacity for imagery was studied in the creativity of students
      in secondary school. Several questionnaires were administered to 1125 students.
      Analysis of scores indicated few significant correlations as well as low
      predictive control between scores on the sensorial modalities of the Betts
      questionnaire, spatial tests, and creativity.

PMID- 9017741
TI  - Effects of grade and conditions of motion on children's interpretation of implied
      motion in pictures.
AB  - Interpretation of motion under three levels of motion cues for 36 kindergarten
      and 36 third-grade children was examined. Analysis indicated that third-grade
      children were more skillful at identifying motion than kindergartners and
      postural cues were more effective than flow lines.

PMID- 9017742
TI  - Effects of perceptual training based upon synthesized voice signals.
AB  - 28 undergraduate students participated in a perceptual voice experiment to assess
      the effects of training utilizing synthesized voice signals. An instructional
      strategy based upon synthesized examples of a three-part classification system:
      "breathy," "rough," and "hoarse," was employed. Training samples were synthesized
      with varying amounts of jitter (cycle-to-cycle deviation in pitch period) and
      harmonic-to-noise ratios to represent these qualities. Before training, listeners
      categorized 60 pathological voices into "breathy," "rough," and "hoarse," largely
      on the basis of fundamental frequency. After training, categorizations were
      influenced by harmonic-to-noise ratios as well as fundamental frequency,
      suggesting that listeners were more aware of spectral differences in pathological
      voices associated with commonly occurring laryngeal conditions. 40% of the
      pathological voice samples remained unclassified following training.

PMID- 9017743
TI  - The diagnostic value of the Bene-Anthony Family Relations Test.
AB  - The aim of this study was to assess whether interning psychologists, who used the
      Bene-Anthony as an evaluation technique in the psychotherapeutic treatment of
      their clients, were of the opinion that the test results deepened their insight
      into the nature of their clients' family dynamics. Subjects were 32 children,
      ages 4 to 16 years, who were referred for evaluation for the presence of
      emotional or specific developmental disorders. The interns were of the opinion
      the Bene-Anthony significantly contributed to their understanding of the family
      dynamics. Family relationships appeared to be more complex after the application
      of the test than they seemed before, and the test also clarified the negative
      nature of the family relationships. The Bene-Anthony may be effectively used for
      evaluation of family systems in which dysfunctionality occurs.

PMID- 9017744
TI  - The age of stopping smoking: the Spanish example.
AB  - In this study we analysed the average age at which smokers in Spain seek
      treatment. The sample of 485 smokers who sought to participate in a smoking
      cessation program by mail had a mean age of 37.5 yr, and the mean reported number
      of cigarettes smoked per day was 26.3. Subjects' age was significantly associated
      with gender, marital status, and the number of cigarettes smoked before
      treatment.

PMID- 9017745
TI  - Hauntings and poltergeist-like episodes as a confluence of conventional
      phenomena: a general hypothesis.
AB  - Hauntings and poltergeist-like episodes are argued to be products of contagious
      reactions to ambiguous environmental or cognitive events. In particular, evidence
      suggests that the subjective and objective effects reported by percipients are
      the function of independent, nonparanoraml etiologies whose constitutions have
      been previously established and described. According to this multivariate model,
      the labeling of ambiguous events as "abnormal" or "paranormal" initiates the
      reactive process which is subsequently sustained by perceptual contagion, i.e.,
      flurries of paranormal observations due self-reinforcing attentional processes.

PMID- 9017746
TI  - Psychological testing variables as predictors of return to work by chronic pain
      patients.
AB  - After multidisciplinary pain treatment, pretreatment psychological testing
      variables were compared for 20 chronic pain patients who were working and 42 who
      were not working. Symptom Checklist-90-R scores for Depression, Anxiety, Phobic
      Anxiety, Psychoticism, Global Severity, and Positive Symptom Distress were lower
      for working subjects as were those on the Beck Depression Inventory. In contrast,
      workers scored higher on self-efficacy to manage pain, self-efficacy to function,
      self-efficacy to manage other symptoms, and over all self-efficacy.

PMID- 9017748
TI  - Conversations between older men and women: turn-taking and topics.
AB  - Five dyads of older men paired with older women were compared on the pragmatic
      variables of turn-taking and topicalization. Men talked longer and more often
      while women served to reinforce and maintain the conversational topics.

PMID- 9017747
TI  - Inhibition in picture naming and word reading.
AB  - Some previous researchers assumed that the underlying process of inhibition is
      similar in the modally pure target-distractor task, e.g., picture-picture task,
      color-color task, and in the modally mixed target-distractor task, such as the
      picture-word task or the color-word task, but some did not. The present purpose
      was to compare the inhibition in the modally pure tasks (word-word task and
      picture-picture task) with that in the modally mixed task (picture-word task)
      through the effects of the two factors, that is, response set and the semantic
      relation between target and distractor. These factors were assumed to affect
      inhibition in some kinds of interference tasks. Analysis showed the effect of
      response set was evident on the picture-picture task but not on the word-word and
      the picture-word tasks. On the picture-word task, only when the distracting word
      was in the same set of the target picture, was the effect of the semantic
      relation exhibited. The differential inhibition for the three tasks was
      discussed.

PMID- 9017749
TI  - Effects of game structure on boys' satisfaction and participation.
AB  - Inhabiting level is defined as the number of tasks to be performed in a setting
      in relation to the number of people who will perform those tasks and has been
      found to influence the behaviors and psychological experiences of participants.
      In this study, the structural organization of a children's game was manipulated
      to create three different levels of inhabiting. Boys (n = 108) were classified as
      having low, medium, or high throwing skills. Teams consisting of one player from
      each skill level were created using stratified random sampling. Teams then played
      an underinhabited game (two ongoing tasks per player), an adequately inhabited
      game (one ongoing task per player), and an overinhabited game (one task rotated
      among three players). Satisfaction with each game was measured by a questionnaire
      following play. Observational rating scales were used to assess players' degree
      of involvement and affective expression during play. Boys reported significantly
      greater satisfaction and displayed significantly greater involvement and positive
      affect in the underinhabited game than in either one or both of the other games.

PMID- 9017750
TI  - Incidence of head injury: lasting effects among college students and working
      adults in the general population.
AB  - 224 (21%) of 1067 persons in a nonclinical population surveyed had one or more
      head injuries resulting in unconsciousness. They had a total of 306 head injuries
      with 113 (31%) of them resulting in lasting neurological effects. Both in a pilot
      project and in the main study, headache was the most commonly reported of an
      array of symptoms that are essentially a postconcussion syndrome.

PMID- 9017751
TI  - Effects of pretest stimulative and sedative music on grip strength.
AB  - The purpose of the present study was to investigate the effects of stimulative
      (energizing) and sedative (relaxing) music on grip strength. A 2 x 3 (gender x
      condition) repeated-measures analysis of variance and post hoc tests showed that
      participants (N = 50) evidenced higher grip strength after listening to
      stimulative music (M = 43.94 kg.force) than after sedative music or a white noise
      control condition. Sedative music yielded lower scores than white noise. Men
      evidenced higher grip strength than women, but there was no interaction between
      gender and music condition. It was concluded that a simple motoric task such as
      grip strength provides a sensitive measure of psychophysical responses to music.

PMID- 9017752
TI  - Matching proprioceptive to visual speed affected by nonkinematic parameters.
AB  - In an experiment three subjects adjusted the speed of a treadmill under their
      feet to match the speed of a flow pattern visible in front of their feet.
      Although the subjects could perform the matching fairly well, their adjustment
      varied with the effort of walking manipulated. This finding rules out a purely
      kinematic-matching hypothesis.

PMID- 9017753
TI  - Covert speech behavior during a silent language recitation task.
AB  - This study tested the prediction that covert speech behavior measured
      electromyographically from the lips is significantly more prominent during a
      brief silent-language recitation task than a brief nonlanguage visualization
      task. Subjects were 20 right-handed, adult volunteers who agreed to participate.
      Subjects were tested in a multiple-baseline reversal design following an ABAB
      procedure whereby A1 and A2 were 30-sec. rest periods. B1 and B2 were
      alternatively assigned 30-sec. silent-language recitation and visualization test
      periods, respectively. Subjects' dorsal lips and nondominant forearm EMG measures
      were taken during resting baseline and testing conditions. In addition, subjects'
      skin surface temperature and heartrate were measured during the rest and test
      conditions. For the silent-language task, subjects were asked to recite
      'mentally' the Pledge of Allegiance to the flag. Subjects were instructed to
      'imagine seeing' the American flag for the visualization task. Subjects' mean lip
      EMG activity increased significantly from rest to the silent-language recitation
      task, while no significant change in mean lip EMG was observed from rest to the
      visualization condition.

PMID- 9017754
TI  - Achievement motivation and involvement in sport competitions.
AB  - 213 pupils (M = 17.2 yr.) were tested on the motive to achieve success, the
      motive to avoid failure, future time orientation, perceived instrumentality of
      cognitive and physical tasks at school, and the involvement in sport
      competitions. Analysis shows a significant positive correlation between the
      scores on motive to achieve success and the amounts of competitive involvement in
      sport. Conversely, the motive to avoid failure was negatively correlated with the
      involvement in sport. Further, a positive significant correlation for the
      involvement in sport competitions with perceived instrumentality of physical or
      sport tasks at school appeared. The relations were similar for both girls and
      boys. An hypothetical model based on hierarchical regression of the data showed
      that all independent variables affected involvement in sport competitions
      directly or indirectly.

PMID- 9017755
TI  - Effects of mental practice on performance are moderated by cognitive anxiety as
      measured by the Sport Competition Anxiety Test.
AB  - 45 subjects were assessed for cognitive anxiety on the Sport Competition Anxiety
      Test. Two months later they observed a person performing a new motor task which
      required high cognitive processing to be performed well. After this observation,
      22 subjects were randomly assigned to a Mental Practice and 23 to a Control
      group. The former performed a cognitive rehearsal of the task, whereas the latter
      did not. None practiced the task physically before being tested. Analysis of
      variance showed that both errors and performance time interacted significantly
      with Mental Practice versus Control group scores and scores on the Sport
      Competition Anxiety Test. Among subjects who practiced mentally, those scoring
      low on cognitive anxiety performed significantly better than subjects who scored
      high. Further, the relationship between test scores of cognitive anxiety and
      performance for the total sample was analysed by different curvilinear regression
      models. The cubic model fitted the data better and accounted for a greater
      percent of variance on error performance explained by anxiety test scores (R =
      .39) than the linear correlation (r = .25). This cubic model formed a polynomial
      relationship between cognitive anxiety test scores and error in performance.

PMID- 9017756
TI  - Voluntary control of breathing pattern in asthmatic children.
AB  - 15 asthmatic children and 15 healthy children were trained to adjust their
      breathing pattern to a target pattern displayed on a video screen by using visual
      feedback. The error scores in the two groups were not significantly different.
      These data did not support the hypothesis that voluntary control of respiratory
      muscles is impaired in asthmatics.

PMID- 9017757
TI  - Time estimation: effects of cognitive task, presentation rate, and delay.
AB  - The variables of which subjective time is a function extend throughout a myriad
      of "people, places, and things." This study measured subjective estimations of
      time as a function of complexity of cognitive task including arithmetic and
      recall (within subjects), the rate of stimulus (digit span) information (between
      subjects), and the delay between stimulus presentation and estimations of time
      (between subjects). A mixed analysis of variance 2 x 2 x 3 (repeated-measures)
      factorial design showed that retrospective time estimations were significantly
      different as a function of the main effects of rate of digit presentation and
      delay. Men and women showed no differences with no significant interactions so
      their data were pooled. Quotient values for ratios of delayed versus immediate
      estimates and slow versus fast rates showed overestimates of "real time."
      Explanations based on the "storage-size model," the "attention-allocation" model,
      and comparisons with Pedri and Hesketh's 1993 data are discussed.

PMID- 9017758
TI  - Chronobiometric assessment of autogenic training effects upon blood pressure and
      heart rate.
AB  - Autogenic training, a method of self-hypnosis, lowers the extent of within-day
      variation of systolic blood pressure assessed by the circadian double amplitude.
      The blood pressure and heart rate of ten patients, conventionally diagnosed as
      having hypertension or white-coat hypertension, were automatically monitored at
      30-min intervals for 7 days before autogenic training and again for 7 days, at 1
      or 2 months after the start of autogenic training (practiced three times daily).
      The circadian double amplitude of systolic blood pressure of the patients
      investigated was 3 to 17 mm Hg lower on autogenic training. In 5 patients,
      reductions by 7 to 17 mm Hg were statistically significant. These results are
      regarded as provisional statistics, the utility of which depends on replication.
      By contrast, the over-all group reduction of the circadian double amplitude of
      systolic blood pressure by 8 mm Hg on the average can be taken at face value.
      Autogenic training also lowered the circadian double amplitude of diastolic blood
      pressure, but the effect was small as was the effect of autogenic training upon
      the MESOR (a rhythm adjusted mean) and acrophase (a measure of the timing of over
      all high values recurring each day). The effect of autogenic training upon the
      circadian double amplitude of systolic blood pressure suggests its trial as first
      line treatment of patients with an excessive circadian blood pressure amplitude,
      a condition which, even in the absence of an elevated 24-hr, average of blood
      pressure, is associated with a large increase in the risk of developing ischemic
      stroke or nephropathy.

PMID- 9017759
TI  - The learning styles of medical students: an annotated bibliography of twenty
      years of research.

PMID- 9017760
TI  - Lateral cradling preferences in children.
AB  - Lateral preferences for cradling a doll and for holding a package were
      investigated among children from 2- to 6-yr-old. Results showed a preference for
      holding a baby on the left side of the body in children as young as 3 yr. old.
      The data favour the hypothesis of an early emergence of this pattern of behavior
      in the human ontogenesis.

PMID- 9017761
TI  - Ibutilide: a new class III antiarrhythmic agent.
AB  - Ibutilide fumarate is a new antiarrhythmic agent recently approved for the
      conversion of atrial flutter (AFl) and atrial fibrillation (AF) to normal sinus
      rhythm. A class III agent in the Vaughan Williams classification system,
      ibutilide prolongs cardiac repolarization by activating a slow inward,
      predominantly sodium current. An alternative or additive mechanism to prolong
      repolarization may be blockade of the outward delayed rectifier potassium rapid
      current. Ibutilide is administered intravenously, and approximately 40% of the
      drug in serum is protein bound. It is eliminated through hepatic metabolism by
      undefined enzyme systems, and it appears that none of the metabolites contributes
      significantly to antiarrhythmic activity. The elimination half-life of ibutilide
      ranges from 2-12 hours. When administered by 10-minute infusion, ibutilide 1 mg
      (approximately 0.015 mg/kg) resulted in conversion to sinus rhythm in 24-58% of
      patients with AFl and 20-32% with AF, compared with about 5% for placebo.
      Administering a second dose of 0.5-1 mg improved the overall response rates to
      approximately 75% and 45%, respectively. In randomized comparative trials,
      ibutilide was more effective than sotalol in converting AFl (70% vs 19%) and AF
      (44% vs 11%) and more effective than procainamide (76% vs 12% and 51% vs 20%,
      respectively). The time to conversion in most trials was usually 20-30 minutes.
      Nausea is the most common noncardiac adverse effect (< 2%). Nonsustained and
      sustained polymorphic ventricular tachycardia occurred in 2.7-6.7% and 1.7% of
      patients, respectively.

PMID- 9017762
TI  - Mirtazapine: an antidepressant with noradrenergic and specific serotonergic
      effects.
AB  - Mirtazapine is a unique antidepressant that refines the specificity of effects on
      noradrenergic and serotonergic systems. It is an antagonist of presynaptic alpha
      2-adrenergic autoreceptors and heteroreceptors on both norepinephrine and
      serotonin (5-HT) presynaptic axons, plus is a potent antagonist of postsynaptic 5
      HT2 and 5-HT3 receptors. The net outcome of these effects is increased
      noradrenergic activity together with specific increased serotonergic activity,
      especially at 5-HT1A receptors. This mechanism of action maintains equivalent
      antidepressant efficacy but minimizes many of the adverse effects common to both
      tricyclic antidepressants and selective serotonin reuptake inhibitors.
      Mirtazapine has an onset of clinical effect in 2-4 weeks similar to other
      antidepressants, although sleep disturbances and anxiety symptoms may improve in
      the first week of treatment. It has minimal cardiovascular and anticholinergic
      effects, and essentially lacks serotonergic effects such as gastrointestinal
      symptoms, insomnia, and sexual dysfunction. Sedation, increased appetite, and
      weight gain are more common with mirtazapine than with placebo. An elimination
      half-life of 20-40 hours enables once-daily bedtime dosing. The recommended
      initial dosage is 15 mg once/day at bedtime, with an effective daily dosage range
      of 15-45 mg. Cases of overdose of up to 975 mg caused significant sedation but no
      cardiovascular or respiratory effects or seizures.

PMID- 9017763
TI  - Proton pump inhibitors and acid-related diseases.
AB  - Proton pump inhibitors (PPIs) are targeted to the gastric acid pump, H+, K(+)
      adenosine triphosphatase (ATPase). The drugs accumulate in the acid space of the
      parietal cell and convert to active sulfenamide by an acid-catalyzed reaction.
      Consequent covalent inhibition of H+, K(+)-ATPase blocks the final step of acid
      secretion, hence the PPIs omeprazole, lansoprazole, and pantoprazole are more
      effective than histamine2-receptor antagonists (H2RAs) in controlling acid
      secretion. Preclinical short- and long-term clinical surveillance data show these
      drugs to be well tolerated and safe. The PPIs heal the lesions of
      gastroesophageal reflux disease and lessen symptoms more effectively and more
      quickly than the H2RAs, and are effective and faster acting for peptic ulcer
      disease. Helicobacter pylori is causally implicated in the majority of peptic
      ulcers and in atrophic gastritis. Since PPIs, but not H2RAs, are synergistic with
      antibiotics in eradicating H. pylori, their use is appropriate in all acid
      related diseases since all patients who are H. pylori positive require
      eradication as well as healing.

PMID- 9017764
TI  - Can insulin therapy delay or prevent insulin-dependent diabetes mellitus?
AB  - Although the precise events preceding insulin-dependent diabetes mellitus (IDDM,
      type 1 diabetes) have not yet been elucidated, it is known that IDDM results from
      a slow, progressive, immune process directed against pancreatic islet beta cells.
      Disrupting this autoimmune process has been the focus of research aimed at
      preventing or slowing the disease progression. Technologic advances in predicting
      the onset and likelihood of developing IDDM have made it possible to study the
      effects of early immune intervention. The National Institutes of Health recently
      launched a large-scale, multicenter trial to evaluate the effectiveness of
      insulin as preventive therapy. Although many different immunosuppressive and
      immunomodulating agents have been investigated, the use of insulin as a
      prophylactic agent is a fairly recent concept. Several methods have been used to
      halt the autoimmune destruction of the pancreas, with animal and human studies
      serving as the basis for insulin in preventing IDDM.

PMID- 9017765
TI  - Rational drug use in the treatment of depression.
AB  - New drugs are being developed for the management of depression in response to the
      growing awareness of the prevalence and disability associated with the disorder
      and the need for agents with improved side effect profiles. All antidepressants
      are equally effective for treating uncomplicated unipolar depression without
      psychotic features. For patients with atypical depression with prominent anxiety,
      agitation, sleep loss, and irritability, monoamine oxidase inhibitors are the
      first choice. Data are accumulating supporting the efficacy of selective
      serotonin reuptake inhibitors (SSRIs) in these depressive subtypes. Factors to
      consider when choosing an antidepressant include spectrum of adverse effects,
      long-term tolerability, dosing schedule, clinically significant drug
      interactions, underlying medical conditions, earlier response to therapy, and
      pharmacoeconomics. Based on these criteria, it is suggested that a trial with the
      SSRIs be attempted first. Venlafaxine and nefazodone are newer agents with
      mechanisms of action that have advantages over tricyclic antidepressants and
      monoamine oxidase inhibitors. Choosing a drug that is effective, tolerable, and
      convenient will improve the likelihood of achieving and maintaining a full
      remission. It will also decrease the morbidity and mortality of this very
      treatable disease.

PMID- 9017766
TI  - Metformin, a promising oral antihyperglycemic for the treatment of noninsulin
      dependent diabetes mellitus.
AB  - Noninsulin-dependent diabetes mellitus has historically been treated with diet
      therapy alone or the addition of an oral hypoglycemic agent such as a
      sulfonylurea, or the two in combination with insulin. Although these medical
      interventions lower blood glucose concentrations, they may also potentiate
      hyperinsulinism through increased serum insulin concentrations. Insulin
      resistance and hyperinsulinism are associated with cardiovascular risk factors
      such as hypertriglyceridemia, decreased high-density lipoprotein cholesterol
      levels, hypertension, and hyperglycemia, among others. Therefore, a desirable
      therapeutic alternative would lower blood glucose, not result in hyperinsulinism,
      and have beneficial effects on lipid profiles. Metformin is a biguanide
      antihyperglycemic agent that provides these effects. When administered to
      carefully selected patients and monitored appropriately metformin may prove to be
      valuable in the treatment of diabetes mellitus and in altering its cardiovascular
      sequelae.

PMID- 9017767
TI  - Antithrombotic therapy after intracoronary stenting.
AB  - Conventional percutaneous transluminal coronary angioplasty may result in
      complications such as abrupt closure and late restenosis. This has led to
      increased application of mechanical revascularization techniques including
      intracoronary stents. In the past, subacute thrombosis after intracoronary
      stenting mandated anticoagulation with warfarin for a minimum of 1 month, with
      aspirin (ASA) started before the procedure and continued indefinitely. New
      information suggests that high-pressure balloon inflation, with or without
      intracoronary ultrasound guidance to ensure successful stent placement, may
      permit reduction in the antithrombotic regimen to ASA, continued indefinitely,
      and ticlopidine, continued for 1-3 months. However, the majority of trials
      supporting this practice are primarily small, nonrandomized, observational
      studies. One randomized study found a lower frequency of cardiac events,
      including thrombosis, as well as fewer bleeding complications with combined
      antiplatelet therapy with ticlopidine compared with anticoagulant therapy with
      phenprocoumon. Intracoronary stenting without anticoagulation, would permit
      shorter hospitalization and lead to cost-savings. This has led many cardiologists
      to administer ASA and ticlopidine without benefit of data from randomized,
      blinded clinical trials. Antithrombotic therapy after coronary artery stenting is
      in an evolutionary stage, and additional information regarding the safety and
      efficacy of ASA and ticlopidine is necessary.

PMID- 9017768
TI  - The pharmacokinetics of TNP-470, a new angiogenesis inhibitor.
AB  - STUDY OBJECTIVE: To characterize the pharmacokinetic profile of TNP-470, a
      synthetic analog of fumagillin that is a potent inhibitor of angiogenesis and
      inhibits neovascularization in several solid tumor models. DESIGN: A dose
      escalation phase I clinical trial. SETTING: The National Institutes of Health.
      PATIENTS: Patients with human immunodeficiency virus-associated Kaposi's sarcoma.
      INTERVENTIONS: The TNP-470 dosage was increased in 13 sequential cohorts using a
      modified Fibonacci escalation scheme (4.6, 9.3, 15.4, 23.2, and 43.1 mg/m2). The
      drug was administered as a 1-hour intravenous infusion. Serial blood samples were
      collected and assayed by reverse-phase high-performance liquid chromatography and
      the pharmacokinetics were characterized. MEASUREMENTS AND MAIN RESULTS: There was
      a linear relationship between the dose of TNP-470 and both area under the curve
      to infinity (AUC[inf]) and time to maximum concentration (Cmax). The Cmax ranged
      between 6.6 ng/ml at the lowest dosage (4.6 mg/m2) and 597.1 ng/ml at the highest
      dosage (43.1 mg/m2). The agent was rapidly cleared from the circulation with a
      short terminal half-life (0.88 +/- 2.5 hr), which is consistent with preclinical
      data. Peak plasma concentrations of AGM-1883, an active metabolite, ranged
      between 0.4 and 158.1 ng/ml. CONCLUSION: Concentrations of TNP-470 that have in
      vitro activity were achievable in vivo. The drug was rapidly cleared from the
      circulation after a single 1-hour infusion. There was considerable interpatient
      variability in the clearance, but no evidence of saturable elimination. If more
      prolonged exposure is necessary for activity, administration of TNP-470 by
      continuous infusion may be suitable.

PMID- 9017769
TI  - Variable furosemide absorption and poor predictability of response in elderly
      patients.
AB  - STUDY OBJECTIVES: To determine the between- and within-patient variability of
      furosemide bioavailability and natriuretic response, and whether four marketed
      products differ in bioavailability and response. DESIGN: Open-label, crossover
      study. SETTING: General clinical research center at an academic medical center.
      PATIENTS: Convenience sample of 17 patients age 65 +/- 6 years receiving
      diuretics for the treatment of hypertension or congestive heart failure.
      INTERVENTION: Each patient received each of five furosemide products (one
      intravenous and four oral tablet formulations) twice in random order for a total
      of 10 treatments. MEASUREMENTS AND MAIN RESULTS: Measurements included absolute
      bioavailability using cumulative amounts of urinary furosemide collected over 8
      hours after oral versus intravenous dosing, and cumulative amounts of urinary
      sodium. Extensive between- and within-patient variability in all measured values
      rendered any differences among the products neither clinically nor statistically
      significant. Mean (+/-SD) bioavailability was 49 +/- 17% (range 12-112%) and
      coefficients of variation with different products were from 25-43%. Coefficients
      of variation for urinary furosemide excretion and urinary sodium excretion were
      also large, 25-42% and 23-51%, respectively. Multivariate analyses that
      incorporated between- and within-patient effects failed to reveal differences
      among the products for bioavailability (F = 1.04, p = 0.403), urinary furosemide
      excretion (F = 1.09, p = 0.371), or urinary sodium excretion (F = 0.97, p =
      0.448). Correlation coefficients were 0.81-0.85 for the rates of sodium and
      furosemide excretion, and half-maximum response using a sigmoid Emax model did
      not differ among products. CONCLUSION: Although furosemide concentration in
      urinary and natriuretic responses showed good correlation, variability in
      bioavailability considerably affects the drug's excretion into urine. Variability
      in absorption both among patients and within an individual patient is great and
      overwhelms any differences in bioavailability among approved furosemide products.
      Switching from one formulation to another will not likely result in any
      predictable change in patient response.

PMID- 9017770
TI  - Long-term effectiveness of enalapril plus extended-release diltiazem in essential
      hypertension.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and safety of a new combination
      product, enalapril-diltiazem ER, when administered over the long term. DESIGN:
      Open-label, titration to response, with treatment lasting 46 weeks after a 6
      week, double-blind phase. SETTING: Medical clinics in the private and academic
      sectors. PATIENTS: Of 265 patients (68% men, 83% Caucasian, mean age 54.9 yrs)
      with essential hypertension (sitting diastolic blood pressure 95-115 mm Hg)
      enrolled, 167 completed the trial. INTERVENTIONS: Patients received either the
      dosage of enalapril-diltiazem ER that they were given during the double-blind
      phase, or were prescribed enalapril 5 mg-diltiazem ER 120 mg once/day. The dosage
      was increased until blood pressure was controlled or to a maximum of enalapril 10
      diltiazem ER 360 mg/day. MEASUREMENTS AND MAIN RESULTS: Combination therapy
      decreased sitting blood pressures by -11.1/-10.6 mm Hg. Overall, 58% of the
      patients achieved a sitting diastolic blood pressure of 90 mm Hg or below at the
      end of the study. There was no evidence of tolerance to the agents'
      antihypertensive effects. The most common drug-related adverse events were cough,
      headache, dizziness, and asthenia or fatigue. CONCLUSION: The combination
      effectively managed essential hypertension when administered on a long-term basis
      and was generally well tolerated. It should improve both compliance and
      management of hypertension.

PMID- 9017772
TI  - Comparative pharmacokinetics of oral ceftibuten, cefixime, cefaclor, and
      cefuroxime axetil in healthy volunteers.
AB  - STUDY OBJECTIVE: To compare the pharmacokinetics of ceftibuten, cefixime,
      ceturoxime axetil, and cefaclor after oral administration. DESIGN: Randomized,
      four-period, crossover study. SETTING: Hospital-based clinical research center.
      SUBJECTS: Healthy adult men and women volunteers. INTERVENTIONS: Single 400-mg
      doses of cefixime and ceftibuten, and 500-mg doses of cefuroxime axetil and
      cefaclor. MEASUREMENTS AND MAIN RESULTS: Serum concentrations were determined by
      high-performance liquid chromatography methods. The mean oral clearances of
      cefixime, cefuroxime axetil, and cefaclor were similar, ranging from 20.4-27.0
      L/hour; clearance of ceftibuten was approximately 4-fold less, 5.45 L/hour. The
      serum half-lives of ceftibuten (2.35 hrs) and cefixime (2.38 hrs) were prolonged
      compared with those of cefuroxime axetil (1.30 hrs) and cefaclor (0.693 hr).
      These agents also differed in terms of time to maximum concentration, time to
      peak plasma level, area under the curve, and apparent volume of distribution, the
      last reflecting differences in biovailability. CONCLUSION: Ceftibuten had a
      relatively high time to maximum concentration and long half-life, resulting in a
      3.5-fold higher area under the curve than cefixime, cefuroxime axetil, and
      cefaclor. These pharmacokinetic data can be used as a basis to compare the four
      oral cephalosporins; however, comparative susceptibility data must also be
      considered.

PMID- 9017771
TI  - The effect of flurbiprofen on steady-state plasma lithium levels.
AB  - STUDY OBJECTIVE: To evaluate the effects of flurbiprofen therapy on the
      pharmacokinetics of lithium. DESIGN: Placebo-controlled, single-blind, crossover
      study. SETTING: University-affiliated hospital. PATIENTS: Eleven healthy women
      with bipolar disorder. INTERVENTIONS: The subjects received therapeutic doses of
      lithium administered as an immediate-release capsule every 12 hours. In addition,
      they received one placebo tablet every 12 hours during phase I and flurbiprofen
      100 mg every 12 hours during phase II of the study. MEASUREMENTS AND MAIN
      RESULTS: Steady-state pharmacokinetic parameters were measured for each phase.
      Lithium trough plasma concentration (Cmin) and area under the curve were
      statistically significantly increased (p < 0.05) when patients received
      flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour
      lithium urine excretion, although the changes did not reach statistical
      significance. Clinically significant increases in Cmin appeared to be associated
      with a greater than 1000-microgram/24 hour decrease in urinary excretion of
      prostaglandin E2. CONCLUSION: Patients with clinically normal renal function may
      experience an increase in lithium levels with the initiation of flurbiprofen
      therapy.

PMID- 9017773
TI  - Patient self-reporting of compliance does not correspond with electronic
      monitoring: an evaluation using isosorbide dinitrate as a model drug.
AB  - STUDY OBJECTIVE: To assess the accuracy of patient-kept diaries relative to
      electronic monitoring of compliance with isosorbide dinitrate prescribed 3
      times/day for ischemic heart disease. DESIGN: Unblinded, prospective, three-phase
      study. METHODS: Patients with coronary artery disease prescribed isosorbide
      dinitrate 3 times/day were asked to record the time of administration of each
      dose in a pocket diary while being monitored for compliance with a computerized
      Medication-Event Monitoring System (MEMS-4) vial that electronically recorded the
      date and time the vial was opened. RESULTS: Sixty-eight stable outpatients with
      documented coronary artery disease who were prescribed isosorbide dinitrate 3
      times/day were evaluated. Based on a prospectively chosen definition including a
      nitrate-free period, the mean (+/-SD) overall compliance rates were 71% (+/-30)
      versus 55% (+/-32) for the patient-kept diaries and the MEMS vials respectively
      (p = 0.001). The concordance between patient-kept diaries and MEMS data indicate
      that 67% of patients overestimate their compliance when using a self-recording
      tool. An average of 30% of diary entries were in error compared with the MEMS
      vial recordings. CONCLUSIONS: Patient-kept diaries statistically overestimate
      actual compliance relative to that determined by MEMS devices. Given the
      prevalence of the use of diaries as the predominant tool on which researchers
      depend to document compliance with study drugs, our findings suggest that this
      practice should be reevaluated specifically when the time of the dose and
      documentation of administration are critical to qualifying the outcome of drug
      therapy. Such is the case with isosorbide dinitrate use in patients with ischemic
      heart disease. Furthermore, the overall poor compliance documented in this study
      suggests that the utility of isosorbide dinitrate prescribed 3 times/day be
      reevaluated as a clinically effective antianginal drug.

PMID- 9017774
TI  - Clinical and economic considerations of vaccination against varicella.
AB  - We evaluated the medical and economic literature pertaining to varicella vaccine
      in healthy children in an effort to provide perspective for both clinicians and
      those responsible for making payment policies. Chickenpox is relatively mild in
      most immunocompetent children; however, disease-related direct and indirect
      medical costs have been estimated at approximately $400 million/year. A vaccine
      effective in preventing the disease is now available in the United States and may
      offset some of these expected costs. Universal vaccination for patients older
      than 12 months of age without history of varicella infection or other
      contraindication is recommended by the American Academy of Pediatrics. It is
      estimated that it would save $0.90/dollar spent and $5.40/dollar spent from
      payers' and society's perspectives, respectively. Thus varicella vaccination is
      cost-beneficial only when considered from a societal perspective.

PMID- 9017775
TI  - Pharmacists' ability to influence outcomes of hypertension therapy.
AB  - We measured the impact of pharmaceutical care on outcomes of antihypertensive
      therapy for patients with elevated baseline blood pressures who were attending an
      urban university-affiliated internal medicine clinic. The intervention group
      received education about hypertension, drug and nondrug management, and
      assistance to enhance compliance. The pharmacist made recommendations to
      physicians regarding pharmacotherapy. The control group received no such
      education, and interventions relating to pharmacotherapy were only physician
      initiated. Over an average follow-up of 5 months, significant-decreases in mean
      blood pressures were noted for the intervention group from baseline to final
      assessment (156.5/144.5 mm Hg systolic, p = 0.001; 91.6/86.9 mm Hg diastolic, p =
      0.01), with insignificant changes in mean pressures in the control group
      (153.7/151.0 mm Hg systolic, p = 0.48; 90.4/87.8 mm Hg diastolic, p = 0.29).
      Comparing the groups, the change in diastolic pressures was insignificant (4.7 vs
      2.6 mm Hg intervention vs control, p = 0.49), but the change in systolic pressure
      was more impressive (12.0 vs 2.7 mm Hg, respectively, p = 0.05). There was no
      significant difference in SF-36 Health Survey scores between groups. A
      significant decrease (p = 0.03) in the SF-36 physical functioning domain was seen
      in the intervention group, but no other significant changes in health-related
      quality of life scores. Pharmaceutical care contributed to improved blood
      pressure control in these patients.

PMID- 9017776
TI  - Communication between pharmacists and patients: the role of place of residence in
      determining the expectations of older adults.
AB  - The relationship between the place of residence of elderly patients and their
      expectations about the content and style of their communication with pharmacists
      was studied. Using stratified random sampling of households, telephone interviews
      were completed in Spring 1994 with 200 rural and 200 urban persons age 65 or
      older currently taking a prescribed drug that they picked up at a pharmacy.
      Respondents were asked about their sociodemographic characteristics, health, and
      experiences with prescription drugs. Factor analysis of items measuring the
      elders' expectations yielded one factor with nine items. Multivariate analysis
      was used to examine the effect of residence while controlling for other
      variables. Subjects currently took 3.2 +/- 2.2 drugs (mean +/- SD). Fifty-two
      percent of rural elders used independent pharmacies, and 83% of urban elders used
      chain pharmacies. On six of the nine items in the expectation scale, rural elders
      held significantly different (higher) expectations for their pharmacists compared
      with urban elders. The most fully specified model contained five variables
      significantly associated with higher expectations: elders who took fewer drugs
      and who had a stroke, angina, osteoporosis, and no coronary heart disease.
      Although place of residence was a significant predictor of elders' expectations
      in the first three models, it was not when drug experiences were added in.
      Overall, older people in different places of residence have dissimilar personal
      and drug characteristics, and pharmacists practicing in different community
      contexts can anticipate encountering different patient expectations.

PMID- 9017777
TI  - Severe necrosis due to paclitaxel extravasation.
AB  - Paclitaxel is an antineoplastic agent derived from the bark of the Pacific yew
      tree that has activity against many tumors including breast and ovarian
      carcinomas. In the past, its extravasation quality has been considered to be a
      local irritant; however, recent reports suggest that the agent may be a vesicant.
      A patient experienced a delayed vesicant reaction to a paclitaxel extravasation
      that resulted in severe necrosis. No acute symptoms were reported at the time of
      extravasation from the 24-hour peripheral paclitaxel infusion. However, on day 11
      the patient complained of severe and progressive pain at the site of
      extravasation. The site was erythematous and had areas of central necrosis
      requiring debridement and closure by a plastic surgeon. Because paclitaxel
      possesses vesicant characteristics, health care professionals should be aware of
      its potential extravasation hazard. Prolonged peripheral infusions should be
      avoided or administered with extreme caution.

PMID- 9017778
TI  - Suspected acute interstitial nephritis induced by piperacillin-tazobactam.
AB  - A 51-year-old woman developed an acute onset of renal dysfunction accompanied by
      rash, lumbar pain, arthralgias, fever, eosinophiluria, and an elevated serum
      creatinine after 6 days of intravenous piperacillin-tazobactam therapy. On
      discontinuing piperacillin-tazobactam and after a 21-day course of prednisone,
      the patient's constitutional symptoms dissipated and her renal function returned
      to baseline. Acute interstitial nephritis has been reported as an adverse effect
      of many drugs, including antibiotics, but not, to our knowledge, after
      piperacillin-tazobactam. The time course of events suggested that piperacillin
      tazobactam was the cause of acute interstitial nephritis in this patient.

PMID- 9017779
TI  - Warfarin-fluoxetine and diazepam-fluoxetine interaction.
AB  - Fluoxetine and its metabolite norfluoxetine are eliminated by oxidative
      metabolism via the CYP450 system and may inhibit the oxidative metabolism of
      other drugs to various degrees. A fluoxetine-warfarin interaction has been
      postulated, but is not well documented in the literature. The elimination of
      diazepam may also be inhibited by fluoxetine. An elderly man was prescribed these
      three drugs in combination and experienced such an interaction. He developed an
      elevated international normalized ratio (INR) and died from a cerebral
      hemorrhage. He also manifested drug delirium secondary to inhibited diazepam
      metabolism. In elderly patients receiving fluoxetine, lorazepam or oxazepam would
      be safer alternatives to diazepam since they are conjugated in the liver.
      Patients stabilized on warfarin should be monitored closely for changes in INR if
      fluoxetine is added or deleted.

PMID- 9017781
TI  - Pharmacologic conversion of atrial fibrillation and atrial flutter to normal
      sinus rhythm: the role of ibutilide.

PMID- 9017780
TI  - Serum sickness associated with 6-mercaptopurine in a patient with Crohn's
      disease.
AB  - A 43-year-old man with a 19-year history of Crohn's disease experienced serum
      sickness with acute lobular panniculitis and vasculitis within 2 weeks of
      initiating 6-mercaptopurine therapy. He had no history of extraintestinal
      manifestations of Crohn's disease or drug allergy. Symptoms included disabling
      joint pain, proteinuria, fever, rash, and malaise. To our knowledge, this adverse
      drug reaction has not been described in association with 6-mercaptopurine.

PMID- 9017782
TI  - New frontiers in asthma therapy: leukotriene receptor antagonists and 5
      lipoxygenase inhibitors. Introduction.

PMID- 9017783
TI  - Arachidonic acid metabolites: mediators of inflammation in asthma.
AB  - Asthma is increasingly recognized as a mediator-driven inflammatory process in
      the lungs. The leukotrienes (LTs) and prostaglandins (PGs), two families of
      proinflammatory mediators arising via arachidonic acid metabolism, have been
      implicated in the inflammatory cascade that occurs in asthmatic airways. The PG
      pathway normally maintains a balance in the airways; both PGD2 and thromboxane A2
      are bronchoconstrictors, whereas PGE2 and prostacyclin are bronchoprotective. The
      actions of the LTs, however, appear to be exclusively proinflammatory in nature.
      The dihydroxy-LT, LTB4, may play an important role in attracting neutrophils and
      eosinophils into the airways, whereas the sulfidopeptide leukotrienes (LTC4,
      LTD4, and LTE4) produce effects that are characteristic of asthma, such as potent
      bronchoconstriction, increased endothelial membrane permeability leading to
      airway edema, and enhanced secretion of thick, viscous mucus. Given the
      significant role of the inflammatory process in asthma, newer pharmacologic
      agents, such as the sulfidopeptide-LT antagonists, zafirlukast, montelukast, and
      pranlukast and the 5-lipoxygenase (5-LO) inhibitor, zileuton, have been developed
      with the goal of targeting specific elements of the inflammatory cascade. These
      drugs appear to represent improvements to the existing therapeutic armamentarium.
      In addition, the results of clinical trials with these agents have helped to
      expand our understanding of the pathogenesis of asthma.

PMID- 9017784
TI  - Asthma pharmacotherapy: current practices and outlook.
AB  - Owing to its high incidence and rapidly increasing prevalence in the United
      States population, and to the billions of dollars in associated costs, asthma is
      a significant public health problem. A variety of pharmacologic agents exist to
      manage asthma, but their efficacies vary, as do their costs. Recently published
      guidelines on asthma management set forth a four-step approach that is guided by
      severity of disease and symptom control. These guidelines also suggest increased
      use of antiinflammatory agents, primarily inhaled corticosteroids, which carry a
      higher cost. Shifts in prescribing patterns among physicians who treat patients
      with asthma indicate that the guidelines are being adopted to some extent.
      However, some reluctance toward widespread use of corticosteroids remains, due to
      potential adverse effects as well as cost considerations. Alternatives to
      increased or high-dose corticosteroid use include combination therapy with long
      acting bronchodilators. Newer medications that have more specific mechanisms of
      action, such as leukotriene synthesis inhibitors and leukotriene receptor
      antagonists, may offer another option.

PMID- 9017785
TI  - Pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors in
      the management of asthma.
AB  - The leukotrienes (LTs), a family of inflammatory mediators arising from the
      metabolism of arachidonic acid via the 5-lipoxygenase pathway, are prominently
      implicated in the pathobiology of asthma. Two classes of LTs, the cysteinyl LTs
      (LTC4, LTD4, and LTE4) and the dihydroxy-LT (LTB4) have been identified, with
      each class acting via distinct receptors. Inhibition of LT-mediated inflammation
      can be achieved by either interruption of 5-lipoxygenase action, thereby
      preventing formation of the LTs, or inhibition at specific LT receptor sites in
      the airway. Both the 5-lipoxygenase inhibitors and the cysLT receptor antagonists
      have thus far demonstrated the capacity to improve pulmonary function and reduce
      symptoms in clinical models of asthma, such as exercise-, aspirin-, or antigen
      induced bronchoconstriction, and to improve pulmonary function in patients with
      mild-to-moderate, chronic stable asthma. The LTs are therefore critical effector
      molecules in some patients with asthma and important targets in the pharmacologic
      management of this disease.

PMID- 9017786
TI  - Exercise-induced bronchoconstriction: elucidating the roles of leukotrienes and
      prostaglandins.
AB  - Exercise-induced bronchoconstriction (EIB) is prevalent among patients with
      symptomatic asthma, especially those with moderate-to-severe airway
      hyperresponsiveness. This phenomenon generally manifests within the first 3-5
      minutes after exercise, during which the forced expiratory volume in 1 second
      (FEV1) markedly decreases. Usually, the FEV1 gradually returns to baseline within
      an hour. Exercise should not be avoided in patients with asthma, since improved
      physical fitness can reduce the minute ventilation associated with a given
      exercise work rate and, thereby, reduce the bronchoconstrictive response. The
      cysteinyl leukotrienes are becoming recognized as important mediators in EIB, and
      prostaglandins (released at least partially as a result of leukotriene
      stimulation) are gaining recognition for their protective effects. Thus,
      pharmacologic agents that either reduce leukotriene activity or enhance
      prostaglandin activity, or agents that do both, may enhance prophylaxis against
      EIB. Currently, beta-agonists and cromolyn sodium are the mainstays of
      prophylactic therapy for EIB.

PMID- 9017787
TI  - Use of allergen bronchoprovocation to screen drugs for anti-asthma activity.
AB  - In the atopic patient with asthma, allergens are an important cause of chronic
      airway inflammation and symptoms. Natural exposure to seasonal allergens, such as
      grass pollen, may result in exacerbation of asthma, increased airway
      responsiveness (i.e., increased susceptibility of the airways to constrict), and
      an increased frequency of emergency room visits. Removal of patients from
      exposure to indoor allergens, such as dust mites, results in a marked reduction
      in symptoms, less airway responsiveness, and a decrease in drug requirements. In
      the pulmonary function laboratory, inhalation of increasing doses of allergen, in
      a safe and controlled manner (allergen bronchoprovocation), produces
      physiological responses similar to those observed after natural exposure. These
      include an immediate decrease in the forced expiratory volume in 1 second (FEV1)
      that is rapid in onset but short in duration (early response), a subsequent
      gradual decline in FEV1 4-8 hours after allergen inhalation that is sustained
      (late response), an increase in airway responsiveness, and infiltration of the
      airway mucosa by inflammatory cells. Drugs that are effective as maintenance
      therapy for chronic asthma generally attenuate the late response to allergen
      bronchoprovocation, and those with antiinflammatory effects (e.g., inhaled
      corticosteroids) also attenuate the allergen-induced increase in airway
      responsiveness and cellular infiltration of the airways. However, the magnitude
      of drug effect in this clinical model does not correlate well with the drug's
      relative efficacy in chronic asthma. In contrast, drugs that have no effect in
      this clinical model, such as calcium channel blockers, ketotifen, and
      antihistamines, are ineffective as maintenance therapy for chronic asthma. Thus,
      it appears that allergen bronchoprovocation is most useful as a screening tool
      for excluding drugs that are unlikely to be effective for chronic asthma and for
      determining whether a drug has antiinflammatory and/or immunomodulatory actions
      on the airway mucosa.

PMID- 9017788
TI  - The use of 5-lipoxygenase inhibitors and leukotriene receptor antagonists in the
      treatment of chronic asthma.
AB  - With the elucidation of asthma as a chronic inflammatory disease, therapeutic
      approaches have shifted from treatment of symptoms with bronchodilators to
      treatment of the underlying disease with antiinflammatory agents. Along with
      concerns about corticosteroid side effects on the part of both physicians and
      patients, this shift has motivated researchers to develop and test new agents
      with antiinflammatory capabilities. The leukotrienes are endogenous mediators
      with three inflammatory effects: they increase vascular permeability, recruit
      other inflammatory leukocytes, and induce bronchoconstriction. A number of
      antileukotriene agents are in various stages of development. Zileuton, a
      leukotriene synthesis inhibitor, has been shown to improve airway function and
      reduce asthma-symptoms, although there is some concern over liver toxicity.
      Zafirlukast, montelukast, and pranlukast, three new leukotriene receptor
      antagonists, have similar benefits and have not been associated with serious
      increases in liver enzymes. It is hoped that new antiinflammatory drugs will
      provide clinicians with targeted and effective asthma treatments that do not bear
      the potential risks of corticosteroid therapy.

PMID- 9017789
TI  - Suppressive effect of ultraviolet B radiation on contact sensitization in mice.
      II. Systemic immunosuppression is modulated by ultraviolet irradiation and hapten
      application.
AB  - Irradiation of mice with ultraviolet-B (UVB) can suppress contact
      hypersensitivity "systemically", even if hapten is applied to the non-irradiated
      skin site. We previously reported the factors influencing UVB-induced "local"
      immunosuppression. To obtain the most effective systemic immunosuppression, we
      further investigated the effect of the following factors on contact
      hypersensitivity to dinitrofluorobenzene (DNFB): UVB dose, dividing exposure,
      timing of sensitization after irradiation, area of exposure, hapten
      concentration, age, and genetic basis. The suppression was enhanced by increasing
      UVB dose. When 1 J/cm2 of UVB was exposed, 4 daily divided exposures (0.25 J/cm2
      x 4) was more suppressive than a single (1 J/cm2 x 1) or double divided (0.5
      J/cm2 x 2) exposure. Five or 10 day intervals between irradiation and
      sensitization induced stronger suppression than 1 or 3 day intervals. When the
      total energy (Joule, J) was kept constant, the exposure of low dose-UVB to a
      large area (0.5 J/ cm2 x 16.45 cm2) suppressed contact hypersensitivity more
      strongly than did high dose-UVB to a small area (2 J/cm2 x 4.11 cm2). When 25 ml
      of DNFB solution was applied, high concentration induced lower suppression. The
      stronger suppression was most prominent in the young (7 week) than in the old (22
      week) mice. No difference was found in the systemic immunosuppression between
      C3H/HeN and Balb/c mice. These results suggest that not only UVB dose but also
      various factors should be taken into consideration to effectively induce systemic
      immunosuppression.

PMID- 9017790
TI  - UVB irradiation decreases the magnitude of the Th1 response to hapten but does
      not increase the Th2 response.
AB  - Exposure of murine skin to low doses of ultraviolet-B (UVB) radiation before
      sensitization with hapten reduces the ability of antigen presenting cells (APC)
      in the draining lymph nodes to initiate contact hypersensitivity responses in
      vivo and results in the induction of hapten-specific suppressor T cells. In the
      present study, we tested the hypothesis that exposure of skin to UVB radiation
      suppresses T cell responses to hapten in vivo by altering the functions of APC,
      resulting in decreased stimulation of Th1 lymphocytes, which mediate contact
      hypersensitivity responses, and preferential activation of Th2 cells. C3H/HeN
      mice were exposed to either a single 2 kJ/m2 dose of UVB or to 400 J/m2 of UVB
      daily from FS40 sunlamps for four consecutive days and sensitized with
      fluorescein isothiocyanate on UV-irradiated skin. Draining lymph node cells were
      collected 18 h after sensitization and co-cultured with nylon wool-purified T
      cells from naive or fluorescein-immunized mice. Unseparated lymph node cells or
      sorter-purified fluorescein-bearing APC from UV-irradiated mice induced less T
      cell proliferation than APC from non-UV-exposed mice. Lymph node cells produced
      less Th1 and Th2-associated cytokines, interferon-gamma and interleukin-4,
      respectively, in response to APC from UV-irradiated animals compared with APC
      from unirradiated, fluorescein-sensitized mice. Thus, low doses of UV radiation
      do not result in preferential stimulation of Th2 response in lymph nodes, and
      results from cloned cell lines may incompletely reflect T cell responses in vivo.

PMID- 9017791
TI  - Threshold level for measurement of UV sensitivity: reproducibility of phototest.
AB  - The ultraviolet (UV) sensitivity is determined by a phototest where the skin is
      exposed to well-defined doses of UV radiation and the resulting erythema is
      graded by visual scoring after 20-24 h. In this study we wanted to estimate the
      reproducibility of erythema assessment in phototesting. Twenty-one healthy
      Caucasians with skin types I to IV were phototested on UV un-exposed buttock skin
      using a xenon lamp solar simulator. Twenty-four hours after UV exposure eight
      physicians independently graded the erythema reactions two times. Data were
      analysed using inter- and intra-observer agreement and kappa statistics, which
      adjusts for agreement that could be caused by chance alone. Observed agreement
      and kappa statistics were found to decrease with increasing intensity of erythema
      and to be lower for skin types III and IV compared to skin types I and II. Intra
      observer agreement was uniformly better than inter-observer agreement. The
      difference between observers assessment could be as much as three clinical
      erythema grades. Physicians's previous experience with phototesting only had a
      minor influence on agreement. In conclusion, phototesting is based on subjective
      assessment of erythema and is not as precise and reproducible as expected.
      Agreement was better for barely perceptible erythema than for erythema with a
      well-defined border and we therefore recommend that the barely perceptible
      erythema reaction should be used for measurement of the minimal erythema dose.

PMID- 9017792
TI  - Sun-protection behaviour and self-assessed burning tendency among sunbathers.
AB  - A total of 805 sunbathing Caucasians were interviewed about sunprotection
      behaviour and self-assessed burning tendency. Sixty-seven percent of the
      interviewed sunbathers used one or more sunscreen factors. Sunscreen-users and
      nonusers were exposed to the sun 206 min and 197 min (P = 0.186), respectively.
      The sunscreen users were exposed to a marginally higher UV dose than non
      sunscreen users, 4.8 SED versus 4.5 SED (P = 0.0348). The rate of sunscreen users
      was significantly higher among subjects who stated that they always were sunburnt
      in the spring when not using a sunscreen than subjects who stated that they never
      were sunburnt in the spring when not using a sunscreen (P = 0.0001). However,
      when comparing subjects that always burn in the spring and subjects that never
      burn in the spring, we found no significant difference between level of the sun
      protection factor (P = 0.11) nor the duration of sun exposure (P = 0.967), nor to
      which UV doses the subjects were exposed (P = 0,562). Furthermore we found that
      the interviewed sunbathers interpreted to "be sunburnt" as more severe than "to
      turn red". Public campaigns recommend the use of sun protection cream when
      sunbathing without using other sun protective strategies; however, the use of sun
      protection cream is inadequate among sunbathers. More education is required to
      persuade those with more sun-sensitive skin to use a higher protection-factor, to
      reduce sun exposure at times when UV radiation is most intense, and to reduce the
      duration of exposure.

PMID- 9017793
TI  - Photohemolytic potency of oral antidiabetic drugs in vitro: effects of
      antioxidants and a nitrogen atmosphere.
AB  - The sulphonamide-derived oral antidiabetic drugs carbutamide, chlorpropamide,
      glibenclamide, glibornuride, gliclazide, glipizide, gliquidone, glisoxepide,
      glymidine, tolazamide and tolbutamide were investigated for photohemolytic
      properties in vitro. Irradiation with a SOL 3 apparatus (solar simulating
      irradiation) revealed hemolysis in the presence of chlorpropamide, glipizide,
      gliquidone, glymidine and tolbutamide (all in the concentration 10(-3) mol/l).
      Except for glymidine, which exerted photohemolysis in the concentration 10(-4)
      mol/l, no hemolytic effects were seen in the concentration of 10(-4) mol/l or 10(
      5) mol/l. Irradiation with TL 12 light bulbs (UVB), a UVASUN 5000 apparatus (UVA)
      or an experimental lamp (visible light) did not induce phototoxic hemolysis with
      either of the test substances. Addition of the antioxidants ascorbic acid, alpha
      tocopherol or superoxide dismutase significantly inhibited the phototoxic
      hemolysis. Investigations carried out in a nitrogen-rich atmosphere reduced the
      hemolysis as well. These findings indicate an involvement of reactive oxygen
      species in the mechanism of action of the hemolytic process in the presence of
      oral antidiabetic drugs.

PMID- 9017794
TI  - A new method for measurement of erythemal irradiance.
AB  - A composite system of four dosimeter materials, nalidixic acid (NDA),
      polysulphone, 8-methoxypsoralen (8-MOP) and phenothiazine, is presented for the
      passive measurement of the UV spectrum. The properties of the materials were
      investigated and found to be suitable to allow the materials to be applied in a
      system to evaluate the UV spectrum. The evaluation of the spectrum reduces by 70%
      the errors arising when only polysulphone dosimeters are employed to measure the
      exposure due to a source spectrum that differs from the spectrum they have been
      calibrated against. Knowledge of the spectrum provides an advantage over the
      Robertson-Berger meter and polysulphone dosimeters, as the biologically effective
      exposure for any biological process may be calculated with better than 20%
      accuracy. The composite system was miniaturised to a size of 3 cm x 3 cm to
      eliminate errors due to spatial variation of the spectrum and to allow the
      application at any site on objects with complicated topography in a similar way
      as polysulphone dosimeters. Unlike the polysulphone dosimeters, the composite
      system does not require calibration against a specific source of UV in order to
      maintain a high degree of accuracy in the collected data.

PMID- 9017795
TI  - Porphyria cutanea tarda and chronic lymphoid leukemia.
AB  - A case of a familial porphyria cutanea tarda (PCT-II) is reported in which the
      clinically overt form of PCT was provoked by factors relating to chronic lymphoid
      leukemia (CLL). Typical lesions of PCT developed on a 55-year-old woman after
      several blood transfusions and chlorambucil treatment. Besides these provoking
      factors, cytomegalovirus (CMV) infection was diagnosed. Erythrocyte
      uroporphyrinogen decarboxylase activity was about 50% of normal in the patient
      and in her two children. This case supports the suggestion that development of
      PCT in patients with hematological disorders is more than coincidental but may in
      fact be provoked by exogenous factors relating to the treatment of leukemia.

PMID- 9017796
TI  - Long-term changes induced by high-dose irradiation of the head and neck region:
      imaging findings.
AB  - High-dose irradiation is an effective treatment for tumors in the head and neck.
      Radiation-induced complications are uncommon but may result in chronic,
      progressive symptoms months or years after therapy. In 19 (1%) of 1,950 patients
      who underwent successful high-dose irradiation of head and neck tumors over a 5
      year period, delayed radiation-induced changes were documented with imaging.
      These changes can be categorized as soft-tissue, bone, and cartilage necrosis;
      fibrosis leading to functional disorders; arteriopathy; central nervous system
      reactions, delayed myelopathy, and cranial nerve palsies; and the development of
      meningiomas. Radiologic features of radiation-induced soft-tissue, bone, and
      cartilage necrosis include inflammatory swelling adjacent to the area of
      involvement; deep gas-containing ulcerations; sclerotic appearance of the
      involved cartilages; fragmentation and sloughing of necrotic bone or cartilage;
      and abscess and fistula formation. Masticator muscle fibrosis appears as an area
      of diffusely increased signal intensity on T2-weighted images and of enhancement
      on postcontrast T1-weighted images. Radiation arteriopathy may manifest as
      occlusion, subocclusive sclerotic or atheromatous plaque, localized mural
      thrombus, aneurysm, or, rarely, spontaneous rupture. In central nervous system
      reactions, imaging findings include demyelination foci in the white matter, focal
      radiation necrosis, and severe brain atrophy. Radiation-induced meningiomas
      display the same imaging features as non-radiation-induced meningiomas at
      computed tomography, magnetic resonance imaging, and angiography, although follow
      up examinations may reveal their more aggressive biologic behavior. Knowledge of
      the radiologic appearance of radiation-induced changes may prevent
      misinterpretations and facilitate treatment.

PMID- 9017797
TI  - Overview of traumatic injury of the thoracic aorta.
AB  - Traumatic injury of the thoracic aorta is a major clinical concern in patients
      who sustain deceleration or crush injuries. Several mechanical factors may
      explain the typical locations of thoracic aortic rupture (aortic isthmus,
      ascending aorta). Understanding these factors and the pathophysiology involved
      helps the radiologist to recognize aortic trauma at various imaging examinations.
      Chest radiography is the initial screening examination, and radiographs are
      evaluated specifically for signs of mediastinal hematoma, an indication of
      significant thoracic trauma. The most important of these signs include loss of
      aortic contour, tracheal deviation, ratio of mediastinal width to chest width,
      deviation of a nasogastric tube to the right of the T-4 spinous process, and
      depression of the left main-stem bronchus (> 40 degrees below the horizontal).
      Computed tomography (CT) is used increasingly when results of chest radiography
      are equivocal. CT can clearly demonstrate mediastinal hematoma, but this finding
      is also mimicked by several entities, including atelectatic lung, thymus, and
      pericardial recesses. Aortography is the standard for diagnosis. Traumatic aortic
      injury is treated urgently with surgical repair. The rare patient who survives
      aortic injury without surgery may develop a chronic pseudoaneurysm.

PMID- 9017798
TI  - Interpretation of chest radiographs in AIDS patients: usefulness of CD4
      lymphocyte counts.
AB  - Specific infections and neoplasms that are complications of acquired
      immunodeficiency syndrome (AIDS) occur within various CD4 lymphocyte count
      ranges. Knowledge of how these counts correlate with radiographic appearances of
      these entities can limit the differential diagnosis because certain conditions
      are uncommon above a specific count. In patients with CD4 lymphocyte counts above
      200 cells/mm3 and radiographic findings of cavitary and noncavitary
      consolidation, bacterial pneumonia and Mycobacterium tuberculosis are the major
      diagnostic considerations. As the CD4 lymphocyte count falls, these infections
      are still common; however, cavitation is seen less frequently with Mycobacterium
      tuberculosis, and unusual bacterial infections, including those caused by
      Rhodococcus equi and Nocardia asteroides, should be considered. In patients with
      counts below 200 cells/mm3, Pneumocystis carinii pneumonia is the most common
      infection, usually manifesting radiographically as a reticular interstitial
      pattern. At CD4 lymphocyte counts of 50-200 cells/mm3, disseminated fungal
      infection and Kaposi sarcoma become prevalent. In patients with advanced AIDS and
      counts below 50 cells/mm3, radiographic nodular or reticular patterns may
      indicate AIDS-related lymphoma and cytomegalovirus and Mycobacterium avium
      intracellulare infections. When CD4 lymphocyte counts are applied to
      interpretation of chest radiographs in AIDS patients, the working differential
      diagnosis of a radiographic pattern can be tailored to the clinical situation of
      a given patient.

PMID- 9017799
TI  - Medical care without radiology: been there, done that.

PMID- 9017800
TI  - Complex disease of the pleural space: radiographic and CT evaluation.
AB  - Pleural space disease is often complex, difficult to diagnose, and problematic to
      manage. At computed tomography (CT), empyema appears as an oblong fluid
      collection with smooth inner margins that compresses and displaces the
      surrounding lung and airways away from the pleural collection. CT findings in
      hemothorax include heterogeneous attenuation of pleural fluid, hyperattenuating
      areas of debris within pleural fluid, and a "fluid-hematocrit" level. Nodular
      pleural thickening at chest radiography or CT indicates a malignant pleural
      effusion; the cross-sectional capability of CT allows scrutiny of all pleural
      surfaces to detect enhancing tumor implants in addition to pleural effusions.
      Pleural plaque, rounded atelectasis, and pleural pseudotumor can mimic neoplastic
      disease on chest radiographs but can often be diagnosed with CT. Bronchopleural
      fistula may also be difficult to diagnose with radiography alone, necessitating
      further analysis with CT. Pleurocentesis fluid containing chyle, cerebrospinal
      fluid, amylase, or hyperalimentation fluid indicates pleural space disease with
      an unusual or iatrogenic cause. Recent advances in image-guided procedures have
      significantly improved treatment options for many complex pleural space
      processes.

PMID- 9017801
TI  - Radiology of ileal pouch-anal anastomosis: normal findings, examination pitfalls,
      and complications.
AB  - Ileal pouch-anal anastomosis (IPAA) is a procedure in which an ileal reservoir is
      constructed after total colectomy and anastomosed to the anus. IPAA is a well
      established option for patients who require surgery for chronic ulcerative
      colitis or familial adenomatous polyposis. Although excellent functional results
      can be achieved with IPAA, the procedure is associated with an appreciable number
      of complications, including small bowel obstruction, pouch fistula, anastomotic
      separation, anastomotic leakage, pelvic infection and abscess, stricture, and
      pouchitis. However, most of these complications do not require surgical
      intervention and can be managed with aggressive medical treatment and delay of
      ileostomy closure. Radiography of the IPAA pouch is routinely performed before
      closure of the diverting ileostomy to evaluate the integrity of the pouch and
      anastomosis. Such radiography can demonstrate many of the complications of IPAA,
      thus allowing identification of patients who may require intervention or delay
      before closure of the ileostomy.

PMID- 9017802
TI  - MR imaging of anorectal Crohn disease: a pictorial essay.
AB  - Magnetic resonance (MR) imaging has proved useful in the evaluation of perianal
      and perirectal lesions resulting from Crohn disease. On T1-weighted MR images,
      sinus tracts and fistulas are hypointense due to their fluid content; on T2
      weighted images, their signal intensity depends on their fluid content and the
      degree of surrounding fibrosis. Other pathologic entities, such as abscesses in
      the ischioanal fossa, may become evident at MR imaging even though they remain
      hidden at digital examination. Rectal wall thickening and perirectal inflammatory
      changes are often seen at MR imaging of the pelvis. The multiplanar capability of
      MR imaging greatly facilitates the detection of fistulous tracts that extend into
      the supralevator space. MR imaging can be helpful to both the surgeon and the
      gastroenterologist in the assessment of perianal and perirectal complications
      arising from Crohn disease and, when necessary, in the planning of surgical
      intervention. MR imaging also recommends itself to the patient because it is
      noninvasive and does not cause discomfort.

PMID- 9017803
TI  - Ureteral duplication and its complications.
AB  - Duplication of the ureters is a common anomaly and is frequently encountered by
      radiologists. Duplication may be either complete or incomplete and is often
      accompanied by various complications. Incomplete duplication is most often
      associated with ureteroureteral reflux or ureteropelvic junction obstruction of
      the lower pole of the kidney. Complete duplication is most often associated with
      vesicoureteral reflux, ectopic ureterocele, or ectopic ureteral insertion, all of
      which are more common in girls than in boys. Vesicoureteral reflux affects the
      lower pole and can be outgrown, as in nonduplicated systems. Ectopic ureterocele
      and ectopic ureteral insertion affect the upper pole. The ectopic ureterocele
      produces a filling defect of variable size in the bladder; it can be identified
      with contrast material studies or ultrasound. Ectopic ureters may function
      poorly, be difficult to detect, and cause enuresis in girls. A fourth
      complication, ureteropelvic junction obstruction, occurs only in the lower pole
      and is seen in more boys than girls. Anatomic variants or anomalies as well as
      suboptimal imaging techniques can either simulate or obscure duplication, making
      diagnosis difficult. However, familiarity with the embryology of duplication and
      an awareness of the potential pitfalls of excretory urography and voiding
      cystourethrography will foster an understanding of the varied appearances and
      associated complications of both incomplete and complete duplication.

PMID- 9017804
TI  - Unusual fat-containing tumors of the kidney: a diagnostic dilemma.
AB  - Unusual fat-containing renal tumors in a series of 27 cases comprised five
      categories: atypical and complicated angiomyolipomas (AMLs) (n = 15), including
      AMLs with extrarenal growth (n = 5), AMLs with undetectable fat (n = 4), and
      hemorrhagic AMLs (n = 6); fat-containing renal cell carcinomas (RCCs) (n = 9);
      lipoma (n = 1); liposarcoma (n = 1); and fat-containing renal oncocytoma (n = 1).
      Fat was present within RCCs by the following mechanisms; lipid-producing necrosis
      within a large RCC (n = 2), intratumoral bone metaplasia with fatty marrow
      elements and calcification within a small RCC (n = 2), and entrapment of
      perirenal (n = 4) or sinus (n = 1) fat by large irregular RCCs. Fat-containing
      RCC must be considered in cases of fat-containing renal tumors, even though the
      presence of intratumoral fat is characteristic of AML. A dedicated computed
      tomography scanning protocol and strict diagnostic criteria are mandatory for
      accurate diagnosis. Malignancy should be suspected on the basis of the following
      criteria: presence of intratumoral calcifications; large, irregular tumor
      invading the perirenal or sinus fat; large necrotic tumor with small foci of fat;
      and association with nonfatty lymph nodes or venous invasion.

PMID- 9017805
TI  - Malignant tumors of the heart and great vessels: MR imaging appearance.
AB  - Fortunately, primary tumors of the heart and great vessels are rare. These
      primary tumors include angiosarcoma, malignant fibrous histiocytoma, high-grade
      and pleomorphic sarcoma, and paraganglioma with pericardial and myocardial
      invasion. Symptoms are often nonspecific and include chest pain and dyspnea.
      Although these tumors are often diagnosed with echocardiography and computed
      tomography, magnetic resonance (MR) imaging currently appears to be the imaging
      modality of choice because of its diverse capabilities, which include multiplanar
      imaging for excellent anatomic definition of the heart, pericardium, mediastinum,
      and lungs; improved morphologic differentiation between tumor tissue and
      surrounding cardiovascular, mediastinal, or pulmonary tissues; dynamic imaging
      with a gated cine-loop acquisition; and assessment of tissue perfusion. The use
      of gadopentetate dimeglumine is helpful in achieving tumor enhancement on MR
      images but is not required. MR imaging is also useful in assessing tumor response
      to surgery, radiation therapy, and chemotherapy.

PMID- 9017806
TI  - Adult renal hamartomas.
AB  - Renal angiomyolipomas, the most familiar of the renal hamartomas, are well known
      to radiologists, despite being uncommon and of limited clinical importance,
      because angiomyolipomas represent one of the few lesions for which a specific
      diagnosis can be achieved on the basis of radiologic findings in the majority of
      cases. Because of the diversity in the relative amounts of various cellular
      components and because of the occasional association with acute hemorrhage, the
      radiologic features of angiomyolipomas can be somewhat varied. At sonography,
      angiomyolipomas appear echogenic with acoustic shadowing. At computed tomography
      (CT), these lesions typically appear as well-marginated, small (< 5 cm in size),
      cortical masses of predominantly fat attenuation with heterogeneous soft-tissue
      attenuation interspersed throughout. Some angiomyolipomas are larger and poorly
      marginated because of hemorrhage. Typical angiomyolipomas are largely composed of
      fat; those uncommon tumors without demonstrable fat cannot be radiologically
      distinguished from renal cell carcinoma. Renal leiomyoma, a lesion that
      pathologically overlaps with angiomyolipoma to some degree, has a quite different
      imaging appearance (ie, homogeneous, without detectable fat) that cannot be
      distinguished from malignant renal lesions.

PMID- 9017807
TI  - Technical aspects of screen-film radiography, film processing, and quality
      control.
AB  - The broad goal of quality control (QC) of screen-film radiography and film
      processing is to provide radiographs of consistent, high quality. Achievement of
      this goal requires attention to several areas, including QC of the screen-film
      system and photographic processor, acceptance testing of all components, and
      skill in analysis of film artifacts to "diagnose" the processor problems causing
      the aberrations. Methods to reduce waste, recycle by-products, and reuse
      resources such as silver are also part of the QC process. To optimize the
      photographic process, one should use the film, chemical solutions, processor, and
      screens and cassettes produced by one manufacturer or the combination recommended
      by the film manufacturer. Important variables in film processing (eg, density,
      density difference, and base plus fog) are recorded on control charts, which plot
      the variables as a function of time and allow easy analysis of changes in
      operating levels. Many variables can affect any component in the screen-film
      imaging system; problems caused by manufacturing batch-to-batch variation, which
      is perhaps the most pervasive variable, can be lessened by purchasing film,
      screens, and cassettes in large batches and of the same batch and by purchasing
      photographic chemicals in concentrated form and mixing them as needed. Acceptance
      testing ensures that the product meets expectations, ensures that its performance
      meets specifications, and establishes the operating level for the ongoing QC
      program.

PMID- 9017808
TI  - Arterial imaging: comparison of high-resolution US and MR imaging with histologic
      correlation.
AB  - The potential roles of intravascular ultrasound (US) and magnetic resonance (MR)
      imaging in evaluating the artery wall and atherosclerotic plaque were compared.
      Excised human femoral and carotid arteries were imaged with a 42-MHz
      intravascular US system and a 1.5-T MR imager equipped with enhanced gradients.
      In-plane resolution was 40-280 microns for US and 156 microns for MR imaging.
      Stained histologic tissue sections were obtained for correlation with the imaging
      findings. Intravascular US and MR imaging both had sufficient resolution and
      contrast to demonstrate arterial layers and allow distinction of atheroma.
      Correspondence between structures identified with the two modalities was
      excellent and in agreement with histologically defined arterial structures.
      Findings on state-of-the-art intravascular US and MR images correlate well with
      histologic findings in normal and diseased arteries. Intravascular US has the
      advantages of speed and resolution, whereas MR imaging demonstrates superior
      contrast in the depiction of atheroma.

PMID- 9017809
TI  - The GI Project: a prototype electronic textbook for high school biology.
AB  - A prototype electronic science textbook for secondary education was developed to
      help bridge the gap between state-of-the-art medical technology and the basic
      science classroom. The prototype combines the latest in radiologic imaging
      techniques with a user-friendly multimedia computer program to teach the anatomy,
      physiology, and diseases of the gastrointestinal (GI) tract. The program includes
      original text, illustrations, photographs, animations, images from upper GI
      studies, plain radiographs, computed tomographic images, and three-dimensional
      reconstructions. These features are intended to create a stimulus-rich
      environment in which the high school science student can enjoy a variety of
      interactive experiences that will facilitate the learning process. The computer
      based book is a new educational tool that promises to play a prominent role in
      the coming years. Current research suggests that computer-based books are
      valuable as an alternative educational medium. Although it is not yet clear what
      form textbooks will take in the future, computer-based books are already proving
      valuable as an alternative educational medium. For beginning students, they
      reinforce the material found in traditional textbooks and class presentations;
      for advanced students, they provide motivation to learn outside the traditional
      classroom.

PMID- 9017810
TI  - Finding the Path: a World Wide Web-based guide for imaging evaluation of patients
      in the emergency department.
AB  - Finding the Path is a problem-based World Wide Web resource that provides
      algorithms for imaging evaluation of emergency department patients. This module
      is designed to guide physicians in the efficient use of diagnostic imaging
      modalities and their appropriate application to emergency department practice.
      The module is composed of interactive case studies that can be accessed either by
      diagnoses or as unknowns. Each case study provides a brief clinical history
      accompanied by pertinent physical and laboratory findings. Users are asked to
      choose the most appropriate and cost-effective diagnostic imaging study and
      receive feedback on their choice. Associated images, findings, and a brief
      discussion of the diagnosis are displayed. Each case is followed by an algorithm
      aimed at promoting efficient and cost-effective use of imaging modalities. In
      addition to its value in clinical practice, the database is a useful radiologic
      teaching tool for residents and medical students. The module is being used at a
      major university as part of the new curriculum for radiologic education.

PMID- 9017811
TI  - Multiloculated cystic liver lesions: radiologic-pathologic differential
      diagnosis.

PMID- 9017812
TI  - Pediatric case of the day. Primary Ki-l-positive anaplastic large-cell lymphoma
      (ALCL) of the chest wall.

PMID- 9017813
TI  - Breast imaging case of the day. Radial scar with micro- and macrocalcifications
      in association with sclerosing adenosis.

PMID- 9017814
TI  - US case of the day. Open-lip schizencephaly with an area of heterotopic gray
      matter and associated absence of the septa pellucida.

PMID- 9017815
TI  - General case of the day. Intralobar sequestration.

PMID- 9017816
TI  - Image interpretation session: 1996. Tracheal amyloidoma.

PMID- 9017817
TI  - Image interpretation session: 1996. Diabetic muscle infarction (DMI).

PMID- 9017818
TI  - Image interpretation session: 1996. Complex sclerosing lesion (radial scar) of
      the right breast masquerading as an occult breast carcinoma.

PMID- 9017819
TI  - Image interpretation session: 1996. Testicular sarcoidosis.

PMID- 9017820
TI  - Image interpretation session: 1996. Traumatic dissection of the internal carotid
      artery (mural arterial dissection).

PMID- 9017821
TI  - Image interpretation session: 1996. Bronchial-associated lymphoid tissue (BALT).

PMID- 9017822
TI  - Imaging interpretation session: 1996. Fibrolipomatous hamartoma of the median
      nerve and macrodystrophia lipomatosa (MDL).

PMID- 9017823
TI  - Imaging interpretation session: 1996. Leiomyoma of the vulva.

PMID- 9017824
TI  - Imaging interpretation session: 1996. Paroxysmal nocturnal hemoglobinuria (PNH).

PMID- 9017825
TI  - Imaging interpretation session: 1996. Right diaphragmatic rupture with torsion of
      the abdominal viscera.

PMID- 9017826
TI  - Recombinant fibre proteins of human adenoviruses Ad9, Ad15 and Ad19: localization
      of the haemagglutination properties and the type-specific determinant.
AB  - The adenovirus fibre carries the type-specific gamma determinant the existence of
      which was suggested by haemagglutination inhibition tests. Furthermore, the fibre
      is thought to be responsible for the agglutination of monkey, rat and human
      erythrocytes. In order to verify that the haemagglutination properties and the
      type-specific gamma determinant are located on the fibre knob domain, several
      recombinant fibre proteins of subgenus D adenoviruses were constructed, expressed
      in HeLa cells and tested in haemagglutination and haemagglutination inhibition
      tests. Our data showed that the epitopes responsible for the interaction with
      erythrocytes and the gamma determinant are located on the fibre knob domain.

PMID- 9017827
TI  - Use of magnetic beads versus guanidium thiocyanate-phenol-chloroform RNA
      extraction followed by polymerase chain reaction for the rapid, sensitive
      detection of enterovirus RNA.
AB  - The current study compares the sensitivity of RNA extraction using magnetic beads
      versus that of a standard extraction method. Streptavadin-coated magnetic beads
      were labelled with a biotinylated, enterovirus-specific oligonucleotide. RNA was
      extracted using labelled beads or guanidium thiocyanate-phenol-chloroform from 1,
      0.1 and 0.01 TCID50/100 microliters of stock coxsackievirus types A9 and B3,
      echovirus type 11, enterovirus type 70 and poliovirus type 1. Each strain was
      tested three times. RNA extraction using magnetic beads was > 50% faster than the
      standard method. The RNA was amplified using RT-PCR, and the products were
      detected using agarose gel electrophoresis; 6/15 and 7/15 samples at an initial
      concentration of 0.01 TCID50/100 microliters were detected using magnetic beads
      or standard extraction, respectively. Negative-stain electron microscopy was used
      to determine that 0.01 TCID50/100 microliters of coxsackievirus B3 contained
      approximately 3 genomes. Thus, use of magnetic beads labelled with an enterovirus
      specific oligonucleotide was less toxic, more rapid and as sensitive as the
      current standard RNA extraction method.

PMID- 9017828
TI  - Sequence analyses of NS3 genes of recent Pakistan and Singapore strains of dengue
      virus types 1 and 2.

PMID- 9017829
TI  - Towards a consensus for a role of Nef in both viral replication and
      immunomodulation?

PMID- 9017830
TI  - The multifaceted role of HIV Nef.

PMID- 9017831
TI  - The positive influence of Nef on viral infectivity.

PMID- 9017832
TI  - The nef gene of human immunodeficiency virus type-1 (HIV1) is required for
      optimal virus replication in fully activated primary T lymphocytes.

PMID- 9017833
TI  - Analysis of Nef-induced MHC-I endocytosis.

PMID- 9017834
TI  - Nef and the Nef-associated kinase.

PMID- 9017835
TI  - The role of HIV1 Nef in T-cell activation: Nef impairs induction of Th1 cytokines
      and interacts with the Src family tyrosine kinase Lck.

PMID- 9017836
TI  - HIV1 Nef: the Machiavelli of cellular activation.

PMID- 9017837
TI  - Regulation of Nef function.

PMID- 9017838
TI  - Analysis of the interactions between Nef and cellular proteins.

PMID- 9017839
TI  - Use of the two-hybrid system to identify cellular partners of the HIV1 Nef
      protein.

PMID- 9017840
TI  - Nasal mechanoreceptors in guinea pigs.
AB  - The characteristics of nasal mechanoreceptors in the ethmoidal nerve (EN) of
      guinea pigs were clarified by electrophysiological identification of their
      responsiveness to transmural pressure, i.e., the inspiratory effort induced by
      tracheal occlusion and probing of the nasal cavity, vestibule or alae nasi of the
      nose. A total of 73 mechanoreceptors were recorded from 18 guinea pigs breathing
      through the nose or a tracheostomy with an isolated nasal airway. Six receptors
      (6/22) in nasal-breathing animals were stimulated by upper airway occlusion, and
      18 receptors (18/22) in tracheostomy-breathing animals were stimulated by
      maintained negative pressure in the nose. Mechanoreceptors responding to probing
      to the nose were found in both experimental set-ups. The mean threshold of
      'pressure'-responsive receptors to negative pressure was very high (-3.87 +/-
      0.95 kPa). Most of the receptors were also examined for response to ammonia
      vapour or instillation of distilled water; only three 'touch'-responsive
      receptors could be stimulated by ammonia and/or distilled water. These results
      suggest low sensitivity to pressure changes and noxious chemical stimuli of
      mechanoreceptors in the EN of guinea pigs.

PMID- 9017841
TI  - Role of aortic chemoreceptors in the hypertensive response to cigarette smoke.
AB  - To determine the role of aortic chemoreceptors in the rise of systemic blood
      pressure (BP) seen with smoking cigarettes, their responses to injecting various
      doses of nicotine (Nic) into the left atrium and to a puff of cigarette smoke
      were studied in 31 cats. The activity of 71% (n = 36) of the chemoreceptor fibres
      was stimulated significantly by a puff of cigarette smoke (delivering
      approximately 10.0 micrograms kg-1 Nic). The mean threshold dose to stimulation
      by nicotine of these fibres was 8.0 micrograms kg-1. The activity of the
      remaining 29% (n = 15) was not stimulated; their mean threshold dose to
      stimulation by Nic was 24 micrograms kg-1. Stimulation of fibres lasted for about
      14 +/- 0.2 sec and the rise in BP was seen for 20-60 sec. By using hexamethonium
      it was established that the stimulation was produced exclusively by Nic contained
      in cigarette smoke. It was concluded that aortic chemoreceptors must contribute
      to the reflex rise in BP produced by smoking cigarettes.

PMID- 9017842
TI  - Effect of ambient temperature on respiratory chemoreflex in unanaesthetized
      kittens.
AB  - We compared the respiratory responses to breath-by-breath alternations of air and
      14% oxygen (hypoxia run), air and 5% CO2 (CO2 run) or air from two gas lines
      (control run) at ambient temperatures of 25-26 degrees C and 30-31 degrees C in
      nine kittens at 3-7, 11-18 and 30-39 days post-natal age. Chemoreflex responses
      were measured from alternations in inspiratory and expiratory variables during
      test runs and compared with those of control runs. At 25-26 degrees C, no
      significant respiratory alternations were present in hypoxia runs at days 3-7,
      while alternations were significant at older ages. In CO2 runs alternation was
      significant at each age group. At 30-31 degrees C, no significant respiratory
      alternation was present in either hypoxia or CO2 runs for any age group. Thus
      respiratory chemoreflexes decrease at a warmer environmental temperature in
      kittens. This may explain how elevated environmental temperature predisposes
      neonates to respiratory failure.

PMID- 9017843
TI  - Development of respiratory chemoreflexes to hypoxia and CO2 in unanaesthetized
      kittens.
AB  - To investigate differences in the postnatal development of the respiratory
      peripheral chemoreflex response to hypoxia and to CO2, we measured the responses
      to switching inspired gas on an alternate breath basis between two air lines
      (control runs), air and 14% oxygen (hypoxia runs) and air and 5% CO2 (CO2 runs)
      in nine kittens studied sequentially during quiet sleep between 3-7, 11-18, 24-31
      and 35-39 days of postnatal age. The response was quantified in terms of the
      breath-by-breath alternations in respiratory volumes, durations and flows. There
      was little response to control runs at any age. The hypoxia response was not
      different from control at days 3-7 but became significantly different at older
      ages. In contrast, the CO2 response was different from control in each age group.
      The pattern of response was different between hypoxia runs and CO2 runs until 35
      39 days, when the patterns became similar. The results show that chemoreflex
      responses to CO2 are present even at an age when hypoxia sensitivity is low.

PMID- 9017844
TI  - Cardioventilatory responses to hypoxia and NaCN in the neotenous axolotl.
AB  - Ventilatory and cardiac responses to hypoxia, sodium cyanide (NaCN), and intra
      arterial injection of atropine, noradrenaline and DL-propranolol were
      investigated in the neotenous axolotl (Ambystoma mexicanum). Hypoxia elicited
      increased gill and lung ventilation and a tachycardia. Gill ventilation and air
      breathing were stimulated by NaCN infused either into the ventilatory water
      stream or into the bloodstream. Cardiac responses to NaCN were complex, with an
      initial bradycardia followed by a tachycardia. In all animals, the tachycardia
      developed subsequent to lung ventilation. Atropine raised resting heart rate and
      abolished the bradycardia elicited by NaCN. Noradrenaline stimulated gill
      ventilation and heart rate but not air-breathing. These responses were not
      abolished by DL-propranolol, and propranolol had no effect on responses to NaCN.
      The results indicate that the axolotl possesses O2 chemo-sensitivity to both
      external and internal milieu, shows similar O2 chemo-reflexes to those of larval
      anurans and air-breathing fish, but does not exhibit the beta-adrenergic effects
      on ventilation observed in water-breathing fish.

PMID- 9017845
TI  - Stimulation of the mesencephalic locomotor region constricts the airways of cats.
AB  - The neural mechanisms causing the airway dilation evoked by exercise are not
      understood. Three candidates are central command, a reflex arising from
      contracting skeletal muscle, and the Hering-Breuer reflex. Activation of the
      latter two mechanisms has been shown to dilate the airways. In contrast, the role
      played by central command in the control of airway caliber is not known. We,
      therefore, tested the hypothesis that stimulation of the mesencephalic locomotor
      region (MLR) in paralyzed decerebrate cats decreased total lung resistance (TLR).
      Electrical stimulation (20-80 microA) of the MLR increased TLR from 28.2 +/- 1.9
      to 38.1 +/- 2.4 cmH2OL-1 sec-1 (24 sites in 19 cats; p < 0.001). Similarly,
      microinjection of picrotoxin, a GABA antagonist, (8 mM, 100-400 nl) increased TLR
      from 26.1 +/- 3.3 to 36.3 +/- 5.4 cmH2OL-1 sec-1 (9 sites in 9 cats; p < 0.02).
      All of the changes evoked by electrical and chemical stimulation of the MLR were
      accompanied by increases in arterial pressure, heart rate, and ventral root
      motoneuron discharge. In contrast, electrical stimulation of the tibial nerve at
      intensities that recruited C-fibers reflexly decreased TLR (12 cats; p < 0.001).
      Our findings provide little evidence for the central command signal originating
      from the MLR in causing the airway dilation evoked by exercise.

PMID- 9017846
TI  - Deflation-related variability of breathing pattern persists with intact upper
      airway.
AB  - In anesthetized, tracheotomized rats continuous negative airway pressure (CNAP)
      augments breath-to-breath variability of the respiratory pattern compared to that
      during continuous positive airway pressure (CPAP). To test the hypothesis that
      loss of airflow regulation by the upper airway was responsible for this increased
      variability during CNAP we measured respiratory pattern regularity in rats with
      intact airways subjected to steady inflating and deflating transrespiratory
      pressures. The coefficients of variation of tidal volume, peak inspiratory flow,
      and rate of change of flow at end-inspiration were larger during deflation
      maneuvers than during inflations, whereas the coefficients of variation of
      inspiratory and expiratory durations were not different. A variable degree of
      expiratory flow retardation often was observed during deflation. We conclude that
      breathing through the upper airway does not prevent the increase in variability
      of the respiratory pattern associated with deflation.

PMID- 9017847
TI  - Relationship between respiratory mechanics and postinspiratory muscle activity
      during muscarinic challenge in rabbits.
AB  - In six spontaneously breathing New Zealand rabbits (weight 2.36 +/- 0.29 kg)
      anesthetized with pentobarbital sodium (35 mg/kg i.v.) airflow, tidal volume, and
      tracheal and esophageal pressures were measured. These allowed the determination
      of breathing pattern parameters, respiratory system and lung resistances,
      elastances, and time constants, total postinspiratory muscle pressure and its
      timing parameters. The measurements were performed: (a) under control conditions;
      (b) after increasing concentrations of aerosolized methacholine (8, 16, 32, and
      64 mg/ml); and (c) after aerosolized atropine (1 mg/ml). Methacholine
      progressively increased intrinsic mechanical load (resistance and elastance) of
      the respiratory system. Total postinspiratory muscle pressure (Pmus,0) increased
      in relation to the increase in elastic load. The duration of postinspiratory
      activity increased mainly because of the decrease in expiratory time. In
      conclusion, increase in inspiratory activity during expiration is due to two
      independent mechanisms controlling the amplitude and the relative duration.

PMID- 9017848
TI  - Effect of inflation on interstitial cuff and pressure in liquid-filled rabbit
      lung.
AB  - Degassed rabbit lungs were inflated to 15 cmH2O pressure with 3% albumin
      solution. To study cuff growth, lungs were frozen in liquid N2 at several (20-120
      min) inflation times. Cuff-to-vessel area ratio measured from frozen lung pieces
      increased with time reaching a maximum value (0.5-0.9) by 1 h. Time constants
      (to) of cuff growth were similar to those (28 min) of the interstitial pressure
      (Pi) response measured by micropuncture at the lung hilum. Pi response was slower
      with saline (to = 84 min) than with albumin. Compared to saline, positively
      charged protamine sulphate increased the Pi response (to = 44 min). Time
      constants for cuff growth and Pi response were smaller at 15 cmH2O than at 5
      cmH2O inflation pressure (30 vs. 60-120 min). Electrical analog models indicated
      a doubling of interstitial resistance with a four-to eight-fold decrease in
      interstitial specific compliance at the higher inflation pressure, the latter
      attributed to nonlinear elastic behavior of lung parenchyma.

PMID- 9017849
TI  - Respiratory mechanics in rabbits ventilated with different tidal volumes.
AB  - Respiratory mechanics was studied in 11 rabbits at tidal volumes (VT) of 6.7, 10,
      and 20 ml/kg. Flow interruptions were performed during the full respiratory
      cycle. The viscoelastic pressure (Pve) was measured as the dynamic elastic
      pressure (Pel(dyn)) after flow cessation minus the static elastic pressure
      (Pel(st)). Static elastic and viscoelastic parameters were determined with
      numerical technique. Static hysteresis was minimal even at large VT. The Pel(st)
      V curve was linear at small VT and in 6 animals at moderate VT. In 5 animals at
      moderate VT and in all animals at large VT, a linear segment with constant
      compliance was followed by a segment with decreasing compliance. The Pve-V curve
      could be described with a linear model only at small VT. A non-linear model was
      needed at increased VT. Compliance increased with VT. Both static and
      viscoelastic behaviours were linear up to larger volume ranges at large VT
      compared to moderate VT.

PMID- 9017850
TI  - Analysis of coordination between breathing and walking rhythms in humans.
AB  - We investigated the coordination between breathing and walking in humans to
      elucidate whether the coordination degree depends more on metabolic load or on
      breathing or stride frequencies and whether coordination causes energetic
      economization expressed by reduction of oxygen uptake (VO2). Eighteen healthy
      volunteers walked on a treadmill at three load levels realized by different
      velocities and slopes. We analyzed the time intervals between step onset and the
      onset of inspiration or expiration related to stride duration (relative phase,
      phi) and computed the relative-phase histogram to assess the degree of
      coordination. The degree of coordination between breathing and stepping enhanced
      with increasing walking speed. Increased work load achieved by slope at constant
      walking speed improved coordination only slightly. No significant VO2 reduction
      due to coordination was found. VO2 was more strongly related to ventilation
      variations occurring during coordination. Also the sympathetic tone reflected by
      the spectral power of heart rate variability was not reduced during coordination.
      We conclude that during walking the coordination degree increases with increasing
      stride frequency and that coordination does not necessarily cause energetic
      economization.

PMID- 9017851
TI  - A theoretical analysis of factors determining VO2 MAX at sea level and altitude.
AB  - When maximal VO2 (VO2 MAX) is limited by O2 supply, it is generally thought that
      cardiac output (QT) is mostly responsible, but other O2 transport conductances
      [ventilation (VA); [Hb]; pulmonary (DLO2) and muscle (DMO2) diffusion capacities]
      may also influence VO2 MAX. A numerical analysis interactively linking the lungs,
      circulation and muscles was designed to compare the influences of each
      conductance component on VO2 MAX at three altitudes: PB = 760, 464 and 253 Torr.
      For any given set of conductances the analysis simultaneously solved six
      equations for alveolar, arterial, and venous PO2 and PcO2. The equations
      represent pulmonary mass balance, pulmonary diffusion, and muscle diffusion for
      both gases. At PB = 760, [Hb], DLO2 and DMO2 were as influential as QT in
      limiting VO2 MAX. With increasing altitude, the influence of QT and [Hb] fell
      while that of VA, DLO2 and DMO2 progressively increased until at PB = 253, VO2
      MAX was independent of QT and [Hb]. Neither the fall in maximal QT nor rise in
      [Hb] with chronic hypoxia therefore appear to affect VO2 MAX. However, high
      values of ventilation, DLO2 and DMO2 appear to be advantageous for exercise at
      altitude.

PMID- 9017852
TI  - Survival of Bacillus megaterium strains in water.
AB  - Cultures of Bacillus megaterium strains, producers or not of poly-beta-hydroxy
      butyrate (PHB+ and PHB-) were submitted to several shift-downs: nutritional (one
      hundred fold dilution in saline water S or artificial fresh water ADA) or
      nutritional and osmotic (one hundred fold dilution in water or W). In all
      conditions tested, the wild type strain survived, duplicated five times and
      sporulated. However, the PHB- mutant strain showed a drastic loss of viability in
      water (< 0.1%) not observed when the shift was only nutritional (S or ADA).
      Discussion was focused on the advantages of the potential use of Bacillus
      megaterium as host for delivering bio-insecticides in waters instead of natural
      hosts such as B. thuringiensis strains.

PMID- 9017853
TI  - 15N estimates of dinitrogen fixation in alfalfa-weeping lovegrass swards under
      field conditions.
AB  - Information on the amount and proportion of alfalfa (Medicago sativa L.) N
      derived from symbiotic N2 fixation is required in order to exploit this source of
      N in alfalfa-weeping lovegrass (Eragrostis curvula Schrad Nees) pastures in
      semiarid Argentina. A field experiment was conducted to determine N2 fixation by
      a legume grown alone or in two different associations with weeping lovegrass,
      using pure or associated lovegrass as the reference crop. On average, alfalfa
      derived over 80% of its N from fixation during the seeding year, equivalent to
      about 140 kg N ha-1. Compared to N2 fixation in the pure alfalfa sward, the
      percentage of N derived from atmospheric N2 in alfalfa increased significantly in
      the associated pastures and even more so by increasing the seeding ratio of both
      crops sown in the same row. The atom % 15N excess in associated grass was
      sometimes slightly lower than that in pure lovegrass, suggesting any possible
      release of N from alfalfa and subsequent uptake by grass to have been small. The
      highest proportion of grass N that could have derived from the legume was
      estimated to be 23% in the second harvest, equivalent to only 6 kg N ha-1.
      Differences in atom % 15N excess of pure and associated grass reference plants
      did not significantly affect the estimated percentage of N derived from
      atmospheric N2 in alfalfa.

PMID- 9017854
TI  - Determination of radial growth rate of colonies of Sclerotium rolfsii F-6656 for
      the evaluation of culture medium, optimum incubation temperature, osmo- and
      halotolerance.
AB  - The measurement of the colony radial growth rate (Kr) on solid medium of colonies
      of Sclerotium rolfsii Proimi F-6656 for the evaluation of scleroglucan production
      medium and other different media, incubation temperature and tolerance to diverse
      concentrations of sucrose and NaCl were studied. The optimum growth temperature
      observed was 30 degrees C. The Kr value reached on the Production Medium used
      (0.66 mm.h-1) showed no differences compared with those of the other media
      tested, indicating that all the requirements for growth were provided. Poor
      growth was only observed on Soil Extract Agar. The fungus tolerated
      concentrations of sucrose from 0.15 to 1.17 M, on both Czapek and production
      medium. Growth was limited by the highest concentrations of sucrose tested (0.88
      and 1.17 M), as indicated by a slower increase in colony size. Addition of 0.86 M
      NaCl to the production medium and YM agar did not inhibit growth completely, but
      decreased the radial growth rate considerably (80 and 70% respectively).

PMID- 9017855
TI  - Molecular genetics and its application to cardiac muscle disease.
AB  - The application of the techniques of recombinant DNA and molecular biology to
      molecular genetics has made it possible to identify any disease-related gene in
      which there is a family of 2 or more generations with 10 or more living affected
      individuals. Several genes have been identified that are responsible for
      cardiomyopathies and of particular interest is familial hypertrophic
      cardiomyopathy which is the most common cause of death in the athlete. Pre
      screening for genetic abnormalities will be possible prior to the development of
      symptoms and, ultimately, such testing will also be used to specify the type of
      exercise to be recommended for different types of athletic training or exercise
      needs.

PMID- 9017856
TI  - Biomechanics of the sprint start.
AB  - Many variables have been studied pertaining to the block sprint start. Research
      suggests that the adoption of a medium block spacing is preferred, with front and
      rear knee angles in the set position approximating 90 and 130 degrees,
      respectively, with the hips held moderately high. The sprinter must be capable of
      developing a high force rate combined with a high maximum force, especially in
      the horizontal direction. This ability to create high force underlies other
      important indicators of starting performance such as minimum block clearance
      time, maximum block leaving velocity and maximum block leaving acceleration. Once
      the sprinter has projected him/herself from the blocks at a low angle (40 to 45
      degrees) relative to the ground, the following 2 post-block steps should occur
      with the total body centre of gravity ahead of the contacting foot at foot strike
      to minimise potential horizontal braking forces.

PMID- 9017857
TI  - Common soccer injuries. Diagnosis, treatment and rehabilitation.
AB  - Soccer is a game with worldwide appeal. Increasing numbers of participants are
      members of all age groups and skill levels. The game presents to the sports
      medicine practitioner a wide variety of musculoskeletal and medical problems.
      Soccer injuries increase in frequency as the age of participant increases, with a
      low incidence of injury in preadolescent players. Musculoskeletal injuries most
      commonly affect the lower extremities and include contusions, acute and chronic
      musculotendinous strains, and ligamentous injuries to the knee and ankle. Most
      injuries are minor and respond to analgesics, therapy modalities and exercise
      therapy. Groin pain is a common problem and particularly prevalent among soccer
      players owing to the game's specific stresses. Other less common but important
      injuries include facial trauma, mild brain injury (concussion) and heat-related
      injury. Team physicians, athletic trainers and physical therapists need to
      possess a basic understanding of the most common injuries and problems in order
      to maximise safe participation for their athletes.

PMID- 9017858
TI  - Physical activity and pregnancy outcome. Review and recommendations.
AB  - The dual stresses of pregnancy and exercise may create conflicting physiological
      demands that could adversely affect pregnancy outcome. Specifically,
      redistribution of uterine blood flow and subsequent fetal hypoxia, hyperthermia
      and the risk of teratogenic effects, decreased carbohydrate availability for the
      fetus, and increased uterine contractility with a possible increase in risk for
      pre-term labour, all pose potential threats to fetal growth and development.
      However, despite these potential risks, literature dealing with exercise and
      pregnancy outcome generally shows neutral or somewhat favourable effects. A few
      studies have found reduced birthweight, shortened gestation, and less gestational
      weight gain among women who continue vigorous exercise during pregnancy compared
      with those who discontinue exercise or who are sedentary. However, most studies
      find little, if any, association between exercise and birthweight or gestational
      age. In contrast, studies of occupational physical activity often show an
      association between heavy physical work and lower birthweight and shorter
      gestation, especially in women in developing societies whose nutritional status
      may be compromised. Standing, in particular, may be associated with increased
      risk of prematurity. Although other outcomes, such as length of labour, type of
      delivery have not been well studied, there is no indication of any negative
      associations with exercise. There is limited evidence which suggests that
      exercise is related to shorter labour and is a useful treatment for gestational
      diabetes. Exercise is also associated with fewer symptoms and discomforts of
      pregnancy. This relationship is temporal in that exercise earlier in pregnancy is
      associated with fewer symptoms later in pregnancy. The lack of evidence for any
      harmful effects of exercise on pregnancy outcome indicates that, for healthy,
      well-nourished women, exercise during pregnancy is safe and subject to few
      restrictions. This conclusion is reflected in the revised, 1994 recommendations
      of the American College of Obstetricians and Gynecologists.

PMID- 9017859
TI  - Body composition of spinal cord injured adults.
AB  - The prevalence of diseases associated with obesity, such as cardiovascular
      disease and diabetes mellitus, is higher in the spinal cord injury (SCI)
      population. Specifically, the mortality rate for cardiovascular disease is 228%
      higher in the SCI population. In addition, 100% of SCI individuals have
      osteoporosis in the paralysed extremities. These diseases are related to physical
      activity level, the level of the spinal cord lesion, and time post injury.
      Physically active SCI men and women have above-average fat mass (16 to 24% and 24
      to 32%, respectively, compared with 15% for able-bodied men and 23% for able
      bodied women), while sedentary SCI individuals have 'at-risk' levels of body fat
      (above 25% and 32%, respectively). The proportions and densities of the 3 main
      constituents comprising the fat-free body (mineral, protein and water) are
      altered following SCI. Bone mineral content decreases by 25 to 50%, and the
      magnitude of reduction is dependent on the level, completeness and duration of
      SCI. Because of denervation resulting in skeletal muscle atrophy, total body
      protein reduces by 30%, and total body water relative to bodyweight decreases by
      15% following SCI. Indirect methods based on 2-component body composition models
      assume constant proportions and densities of mineral, protein, and water in the
      fat-free body. As a result, prediction equations based on 2-component models
      yield invalid estimates of fat and fat-free mass in the SCI population.
      Therefore, future research needs to directly quantify the proportions and
      densities of the constituents of the fat-free body in the SCI population relative
      to age, sex, physical activity level, level of the spinal cord lesion and time
      post injury, and to develop equations based on multicomponent body composition
      models.

PMID- 9017860
TI  - Partial meniscectomy and osteoarthritis. Implications for treatment of athletes.
AB  - The biphasic ultrastructure of the meniscus and of articular cartilage provides
      their function in the complex biomechanics of the knee joint including load
      distribution, shock absorption, viscoelasticity, a smooth low friction gliding
      surface and resilience to compression. Meniscectomy may lead to destruction of
      cartilage and to osteoarthritis of the knee joint. Osteoarthritic changes after
      meniscectomy have been reported in up to 89% of patients. Retrospective analysis
      after open or arthroscopically assisted meniscectomy revealed restriction in
      sports to be between 2 and 50% and cessation of sports to be between 2 and 25%.
      Generally, patients with degenerative changes at the time of surgery are reported
      to have lower knee joint function and to resume sports activities later.
      Pharmalogical measures to treat osteoarthritis following previous meniscectomy
      include pain medication and intra-articular drug administration. Additionally,
      range of motion and strengthening exercises and moderate athletic activities are
      recommended. When surgery is considered, correctional osteomies and
      unicompartmental or total knee arthroplasty depending on the degree of
      osteoarthritis are preferred.

PMID- 9017862
TI  - Diagnosis of subclinical cryptosporidiosis in captive snakes based on stomach
      lavage and cloacal sampling.
AB  - The applicability of stomach lavage and cloacal swab techniques for diagnosis of
      subclinical cryptosporidiosis were tested in eight captive snakes subclinically
      infected with Cryptosporidium serpentis. Two feeding regimes were employed. The
      snakes were first fed 7 days prior to stomach and cloaca sampling, and then 3
      days prior to sampling, and the oocysts were detected by fluorescein labeled
      monoclonal antibody (mAb) and by acid-fast stained (AFS) direct wet smear (DWS).
      The overall sensitivity of AFS DWS was 95% for stomach samples and 57% for
      cloacal samples, with false-negativity of 5% and 43%, respectively. A significant
      relationship (P < 0.01) was found between stomach and cloacal samples when mAb
      were used for oocyst detection. Stomach sampling was diagnostically superior to
      cloacal sampling for identifying snake subclinical cryptosporidiosis. Based on
      gastric aspirates, cryptosporidial infection was diagnosed in all eight animals,
      and only in two or four snakes when cloacal swab material was processed by AFS or
      by mAb, respectively. Feeding snakes 3 days prior to sampling facilitated
      diagnosis based on stomach samples; however, it did not improve diagnosis when
      cloacal samples were used. The fraction of oocyst-positive stomach samples was
      significantly higher (P < 0.05) for snakes fed 3 days prior to gastric lavage
      when compared with the fraction of positive samples of snakes fed 7 days prior to
      lavage. If subclinical cryptosporidiosis is suspected in a non-eating snake
      patient, force-feeding and stomach lavage, 3 days after the meal, is recommended.

PMID- 9017861
TI  - Development and validation of an indirect enzyme immunoassay for detection of
      antibody to Anaplasma marginale in bovine sera.
AB  - An indirect enzyme immunoassay (IELISA) for detection of bovine antibody activity
      to Anaplasma marginale was developed. This assay used a crude antigen prepared
      from erythrocytes of infected calves, immobilized in a polystyrene matrix and a
      mouse monoclonal antibody to bovine IgG1, conjugated with horseradish peroxidase.
      Negative sera (n = 1842) were tested and the diagnostic specificity was 98.4 +/-
      0.6% before retesting 29 positive samples. After retesting, eight samples
      remained positive and the specificity was calculated to be 99.6 +/- 0.3%. The
      diagnostic sensitivity, using 831 serum samples collected from naturally or
      experimentally infected cattle in Argentina, 370 from Mexico and 525 sera from
      experimentally vaccinated or infected cattle from Texas, was 87.3 +/- 1.6%.

PMID- 9017863
TI  - Viability of the sporocysts of Sarcocystis cruzi after exposure to different
      temperatures and relative humidities.
AB  - The effect of temperature and relative humidity (RH) on the survival of
      sporocysts of S. cruzi were investigated in vitro. Under all experimental
      conditions (temperature of 4 degrees C, 37 degrees C, or room temperature; RH of
      18%, 75%, or 100%) some sporozoites retained their viability to excyst for at
      least 90 days. The best conditions for survival were 4 degrees C at 100% RH (more
      than 240 days) and 37 degrees C at 18% RH (more than 180 days). Sporocysts
      maintained at room temperature at all humidities had the lowest level of
      survival. It is concluded that sporocysts of S. cruzi are able to survive in most
      environments for several months and that the fluctuation of the daily ambient
      temperature is likely to influence the viability of the sporocysts.

PMID- 9017864
TI  - Prevalence of intestinal parasites, including Cryptosporidium parvum, in dogs in
      Zaragoza city, Spain.
AB  - Faecal samples from 81 dogs aged between 2 months and 13 years were collected in
      the small animal clinic (37 domestic dogs) and the animal shelter (44 stray dogs)
      located in the Faculty of Veterinary Sciences in Zaragoza city (northeast Spain)
      and screened for the presence of Cryptosporidium oocysts. Faeces were
      concentrated by the formalin-ethyl acetate method and smears of the sediment were
      stained by using the modified Ziehl-Neelsen technique. Cryptosporidium parvum
      oocysts were detected in six dogs (7.4%) aged from 2 months to 6 years. Infection
      was detected in both domestic (three) and stray (three) dogs and all of them
      excreted few oocysts (0-1 oocyst per 20 x field). No statistically significant
      differences in prevalence occurred between dogs younger than 6 months (11.8%) and
      the older dogs (6.2%). Prevalences were not significantly different between
      domestic (8.1%) and stray dogs (6.8%). Diarrhoea was recorded in three of the
      positive dogs (50%), although additional enteric parasites such as oocysts of
      Isospora spp. were also detected in their faeces. Nevertheless, prevalence was
      significantly higher in diarrhoeic (30%) versus non-diarrhoeic (4.2%) dogs (P <
      0.05). Cryptosporidium was one of the parasites most frequently detected in the
      dogs surveyed.

PMID- 9017865
TI  - Prevalence of porcine neonatal isosporosis in Brazil.
AB  - The prevalence of Isospora suis and clinical signs of isosporosis were observed
      in 33 swine farms from 20 sites in the southeastern state of Sao Paulo, Brazil.
      The study was performed by collecting 177 faecal samples from nursing and weaned
      piglets. A history of clinical neonatal isosporosis, as well as the type of
      farrowing and nursery houses and the pig management in the farms were correlated
      to the prevalence of I. suis oocysts. Six faecal samples were collected in each
      of the farms (two from groups of 10- to 19-day-old piglets, two from groups of 20
      to 29-day-old and another two from groups of 30- to 50-day-old pigs). Faecal
      consistency was also registered at the time of their collection. Chi-square tests
      were used for statistical analysis. Oocysts were more prevalent in farms with a
      history of neonatal isosporosis than in those without previous cases. Faecal
      consistency was not related to oocyst elimination. In farms with a history of
      clinical isosporosis, faecal samples from groups of 10- to 19-day-old piglets
      showed a higher prevalence of oocysts than the groups of other ages studied.
      There was no difference in the prevalence of oocysts between nursing and weaned
      piglets. Oocysts were more prevalent in faecal samples collected from dirty
      cemented floors than from self-cleaning floors in the farrowing houses. Types of
      floor and pig management in nursery houses were not associated with the presence
      of oocysts in weaned pigs.

PMID- 9017866
TI  - Comparative efficacy of Freund's and Montanide ISA50 adjuvants for the
      immunisation of goats against heartwater with inactivated Cowdria ruminantium.
AB  - Two vaccines, based on inactivated elementary bodies of Cowdria ruminantium, one
      formulated in Montanide ISA50, the other in Freund's adjuvant, were compared in
      goats. Administered twice subcutaneously with an interval of 81 days, both
      protected three out of five goats against a very severe challenge, lethal for all
      14 control goats, 3.5 months after the second injection. Both vaccines elicited
      similar antibody levels. The protection afforded by the Montanide ISA50 vaccine
      was tested 15 and 17 months after the second injection of the vaccine. Three out
      of six and five out of six goats, respectively, survived a challenge which killed
      all four control goats used on each occasion. Antibodies were still detectable in
      the immunised goats. The level of protection appears to be influenced by the dose
      of virulent C. ruminantium used for the challenge. As any stock of C. ruminantium
      can be incorporated in order to cover the antigenic repertoire of the organism,
      this kind of inactivated vaccine can now be tested in the field.

PMID- 9017867
TI  - Improvement of a polymerase chain reaction assay for the detection of
      Echinococcus multilocularis DNA in faecal samples of foxes.
AB  - A polymerase chain reaction (PCR) method was developed in order to permit a
      sensitive and specific identification of Echinococcus multilocularis DNA from fox
      faecal specimens. In an attempt to overcome problems related to the presence of
      endogenous PCR inhibitors in faecal extracts, we investigated a DNA extraction
      technique using an anion binding resin (Gene-Fizz). This simple and rapid
      procedure was applied to 61 faecal samples. Compared with the traditional
      microscopic examination, the sensitivity of PCR using Gene-Fizz was 82.3% and the
      specificity was 95.5%. No PCR signal was obtained for 20 Echinococcus granulosus
      isolates, showing that this method allowed discrimination between E.
      multilocularis and E. granulosus. Large-scale epidemiological surveys of fox
      excrements may be possible by using Gene-Fizz treatment prior to PCR
      amplification reactions.

PMID- 9017868
TI  - Efficacy of an albendazole slow-release capsule for the control of susceptible or
      resistant nematode parasites of dairy goats.
AB  - The efficacy of albendazole slow release capsules-ASRC- (Proftril-Captec) on
      gastro-intestinal nematodes of dairy-goats was assessed both for benzimidazole
      (BZ) susceptible and resistant strains. For BZ susceptible strains, the efficacy
      of ASRC, assessed by controlled test, ranged from 92% for Trichostrongylus
      colubriformis to more than 99% for Haemonchus contortus on existing worm burdens.
      The administration of the ASRC prevented infection with the same strains for 85
      to 91 days post treatment. In a dairy goat farm, where both in vitro and in vivo
      tests indicated a high level of BZ resistance, the efficacy of ASRC on present
      infections, assessed by Faecal Egg Count Reduction test, ranged from 20 to 60%
      according to the sampling date (13 to 88 days post treatment). On the same farm
      the ASRC given at turnout to non infected (primiparous) goats prevented egg
      shedding up to 72 days (30 for controls). In contrast the ASRC given to infected
      (multiparous) goats did not prevent egg shedding. The present results show that
      the ASRC is an efficient device for controlling BZ susceptible nematodes. The
      ASRC prevents infection with BZ resistant larvae whereas existing infections are
      not reduced.

PMID- 9017869
TI  - The influence of stocking rate on gastrointestinal nematode infections of sheep
      over a 2-year grazing period.
AB  - Six groups of four ewes with twin lambs grazed six paddocks during two
      consecutive seasons from May to September in a two-factorial study on stocking
      rate (9, 13 and 17 ewes ha-1) and infected (designated I-low, I-medium and I
      high) versus clean pasture (C-low, C-medium and C-high). All animals were treated
      with anthelmintic at turn-out and the C-groups were further treated fortnightly.
      The two sets of paddocks received 0, 80 and 160 kg N fertilizer ha-1 annually
      with increasing stocking rate. Ewes were withdrawn at the end of July, and all
      lambs were slaughtered at the end of the grazing season for total worm counts.
      Nematode infections were subclinical during the first year. The second year,
      diarrhoea and soiled hindquarters were present from early August onwards in all I
      groups with highest incidence at high stocking rate. The faecal egg counts of I
      ewes were similar the first year but were substantially higher in I-medium and I
      high compared with I-low in the second year. The lambs had differences in faecal
      egg counts related to stocking rate both years (P < 0.05) and group I-high had
      faecal egg counts ten-fold higher than I-medium and I-low at the end of the
      second year. A significant effect of the interaction of stocking rate times +/-
      infection was found in serum-pepsinogen levels in lambs (P < 0.05). Worm burdens
      (predominantly Trichostrongylus vitrinus, Ostertagia circumcincta and Nematodirus
      filicollis) were not related to stocking rate in lambs at the end of the first
      year whereas there was a significant effect of stocking rate on T. vitrinus
      burdens the second year. Pasture larval counts and results of tracer lambs
      indicated a positive relationship between stocking rate and pasture infectivity.
      It is concluded that the level of ovine nematode infections, especially
      Trichostrongylus spp., in weaned lambs increased with increasing stocking rate
      even though pasture production was enhanced by increased rates of fertilizer
      application.

PMID- 9017870
TI  - Monthly fluctuations of worm burdens and hypobiosis of gastrointestinal nematodes
      of calves in extensive management systems in the Pyrenees (Spain).
AB  - Monthly fluctuations of worm burdens and arrested development of gastrointestinal
      nematodes in cattle from a mountainous region of Spain were studied. Fourteen
      previously helminth-naive calves grazed together with a herd of 120 cattle from
      May to November following the traditional extensive grazing system used in
      mountainous regions of Spain (permanent calves). Each month, throughout the
      grazing season, two helminth-naive calves (tracer calves) were added to the herd
      and allowed to graze for 4 weeks. Every 2 weeks, throughout the grazing period,
      faecal and blood samples from the permanent calves, and pasture grass samples for
      larval recovery were collected. Every 4 weeks, throughout the grazing period, two
      tracer and two permanent calves were removed from the herd and housed on concrete
      for 2 weeks before being slaughtered. The nematode parasite species identified
      from the animals were: Ostertagia ostertagi, O. lyrata, Teladorsagia
      circumcincta, Trichostrongylus axei, Cooperia oncophora, Trichostrongylus
      longispicularis, Capillaria bovis, Nematodirus helvetianus, Oesophagostomum
      radiatum, Chabertia ovina and Trichuris spp. O. ostertagi was the predominant
      species, followed by C. oncophora and T. axei. The highest numbers of worms
      recovered from the tracer calves were observed in May, June, September and
      November with average worm burdens of 4050, 3775, 2775 and 2825, respectively.
      These dates corresponded with 2 months of spring grazing in areas below 1000 m
      (May-June), the last month of grazing in areas higher than 1000 m (September),
      and the last month of autumn grazing in areas below 1000 m (November),
      respectively. The highest total worm burden (8000 worms per animal) was observed
      in the permanent calves in June after 2 months of grazing below 1000 m. The
      average total worm burden in the permanent calves during the study was 5825 worms
      per animal. As in other cool temperate regions of the Northern hemisphere, the
      highest percentage of larval inhibition was observed in autumn, with maximum
      levels of 63.4% for Ostertagia spp. and 89.3% for Cooperia oncophora. Similar
      inhibition levels were observed in parasites from both tracer and permanent
      calves, indicating that previous exposure was not the primary cause of larval
      inhibition.

PMID- 9017872
TI  - Characterization of antigen presenting cells and T-cells in progressing scabietic
      skin lesions.
AB  - Experimentally infested dogs expressed successful adaptive immunity and self
      cured of scabies after previously having scabies that required treatment to cure.
      A biphasic increase and decrease of CD1a+ Langerhans cells (LCs) in the epidermis
      of hosts infested the first time (sensitized) and infested a second time
      (challenged) suggested that these cells were actively involved in the hosts'
      early immune response to scabies. In contrast, in the dermis CD1a+ cell densities
      during both infestations increased to a single peak that followed the first peak
      of these cells in the epidermis. In addition, there was an influx of T
      lymphocytes (CD3 epsilon + cells) and CD11c+ cells into the dermis following the
      first peak of LCs in the epidermis. The influx of T-lymphocytes in the dermis
      coincided with the peak density of CD1a+ cells in the dermis and epidermis during
      the second infestation. In both the epidermis and dermis, MHC Class II+ cell
      density profiles were similar to that of CD1a during the first infestation and
      then exhibited single peaks during the second infestation. The increases in
      CD1a+, CD3 epsilon + (T-lymphocytes), CD11c+, and MHC Class II+ cell responses in
      the dermis occurred earlier and were more intense in the challenge infestation
      compared with the first infestation. These data indicate that T-lymphocytes (CD3
      epsilon +), CD11c+, MHC Class II+, and CD1a+ cells in the dermis played a major
      role in the successful immune response to scabies mites.

PMID- 9017871
TI  - Serologic survey of trichinellosis in wild mammals kept in a Mexico City Zoo.
AB  - A serologic survey of Trichinella infection was carried out to determine the
      prevalence of this parasitosis among wild mammals kept in captivity at the
      Chapultepec Zoo. This was prompted by the necropsy finding of a heavy Trichinella
      infection in a Canadian polar bear (Ursus maritimus) that had been kept at the
      Zoo for more than 11 years. The parasites recovered were identified as T. nativa
      (T2). A serologic study based on ELISA and Western blot analysis was performed in
      serum samples from two polar bears (U. maritimus), six wolves (Canis lupus); nine
      foxes (Urocyon cinereoargenteus); seven coyotes (Canis latrans); nine jaguars
      (Panthera onca); ten lions (Panthera leo); 11 tigers (Panthera tigris); six
      panthers (Panthera pardus); eight leopards (Panthera pardus); two lynxes (Lynx
      rufus); five pumas (Felis concolor); one yagouaroundi (Felis yagouaroundi); and
      one ocelot (Felis pardalis). In these assays, 25% and 27% of the samples studied
      were positive using total muscle larva extract from T. nativa (T2) or T. spiralis
      (T1), respectively. When T. spiralis (T1) excretory/secretory products or
      surface/stichosomal antigens were used, 15 and 13% positivity was obtained
      respectively. The reactivity rates obtained among the different groups varied
      from 11 to 83%, wolves having the highest infection rate. Western blot analysis
      of positive ELISA sera showed an antigenic recognition pattern characteristic of
      animals infected with Trichinella.

PMID- 9017873
TI  - The development of cockle, a sheep pelt defect, in relation to size of
      infestation and time of exposure to Bovicola ovis, the sheep-biting louse.
AB  - Groups of ten louse-naive lambs were infested with one, ten or 100 female
      Bovicola ovis and killed 84 days later when an examination of their pelts was
      made to detect cockle. In a second experiment groups of ten lambs were infested
      with ten or 100 female B. ovis and groups of lambs were killed every fortnight up
      to 84 days post-infestation. The pelts were examined in order to detect the
      earliest time at which cockle could be detected following a louse infestation.
      Cockle is a nodular condition of the skin arising in response to infestation with
      B. ovis and is possibly a hypersensitivity on the part of some sheep to antigens
      of louse origin. In the first experiment cockle did not develop in lambs that had
      remained louse free or which had been initially infested with one louse. However,
      five of ten lambs that had been infested with ten lice and all lambs that had
      been infested with 100 lice developed cockle. In general cockle severity was
      positively related to the size of the terminal louse population. Group mean louse
      counts only slightly exceeded the initial infestation in the lambs infested with
      either ten or 100 lice, and were less than the initial infestation in lambs given
      only one louse. In the second experiment cockle was first seen 54 days post
      infestation, but only in sheep infested initially with 100 lice.

PMID- 9017874
TI  - Faecal examination of Fasciola eggs fixed with formalin solution using the beads
      technique.
AB  - Faecal examination for Fasciola eggs which were preserved in 5% and 10% formalin
      and TAF solutions for 6 years was carried out using the Beads technique. The
      morphological characters and the distinctive yellowish color of Fasciola eggs
      were retained and appeared similar to those of fresh eggs. The mean egg recovery
      rate of eggs in TAF solution was significantly lower than the others (P < 0.01).
      The egg recovery rates from 5% and 10% formalin samples were 57.2% and 60.8%,
      respectively, and these values were similar to the value of 58.8% for fresh
      Fasciola eggs in cattle faeces. For Paramphistomum eggs, preserved with 5%
      formalin, the mean egg recovery rate was 64.7%. Fasciola eggs and Paramphistomum
      eggs were easily identified by their morphological characters in this experiment.
      The present data demonstrated that preservation with 5% formalin solution is an
      acceptable means of storing faecal samples for later examination of Fasciola and
      Paramphistomum eggs using the Beads technique and presumably by other fluke
      sedimentation methods.

PMID- 9017876
TI  - Camel tick (Acari:Ixodidae) control with pour-on application of flumethrin.
AB  - The pyrethroid flumethrin (Bayticol) was tested in camels (Camelus dromedarius)
      as a pour-on for the control of the camel tick, Hyalomma dromedarii. Two, small,
      naturally infested camel herds, one heavily infested and the other lightly
      infested, each composed of eight head of animals, were used for this field trial.
      In each herd, four camels were randomly selected for treatment and the other four
      untreated camels were kept as controls. The heavily infested herd was treated
      with 2 ml 10kg-1 body weight per animal whereas the lightly infested herd was
      treated with 1 ml 10kg-1 body weight per animal. Comparison of the number of
      adult ticks on treated animals with those on untreated ones revealed that there
      were high figures of percentage control within 2 weeks after the application of
      both dose rates. No side-effects of treatment were observed. This trial has
      demonstrated that flumethrin is safe and effective when used to control ticks on
      dromedaries, and the pour-on method for insecticide application is fast and easy
      and is suitable for use by camel owners in the desert.

PMID- 9017875
TI  - A possible explanation of the apparent breed-related resistance in cattle to bont
      tick (Amblyomma hebraeum) infestations.
AB  - Adult male Amblyomma hebraeum tick infestations and the weights of 20 Brahman
      steers and 38 Mashona heifers were measured at different periods at the
      Veterinary Quarantine Area at Mbizi, Zimbabwe. The experiment for the Brahmans
      lasted 108 weeks and that for the Mashona for 113 weeks. The Brahman steers
      weighed a maximum average of 478.4 kg (SE 7.9 kg), which was significantly
      different to the Mashona heifers maximum average of 391.4 kg (SE 5.6 kg) (P <
      0.001). The Brahmans had a maximum average of 112.1 (SE 18.5) adult males, while
      the Mashona heifers had a maximum average of 59.8 (SE 4.3). The difference was
      statistically significant (P < 0.05). There was no statistical difference between
      the two maximum average ticks per kilogram liveweight (P > 0.05). When
      differences in size are corrected for, then breed-related differences disappear.
      It is emphasized that the influence of confounding factors, especially time,
      cannot be corrected for in a satisfactory manner. Therefore, these statistical
      results should be regarded as illustrative rather than proof. To confirm these
      results, it is suggested that the authors of earlier studies should reanalyze
      their databases in a similar manner. It is important that such analyses be
      conducted, or new experiments carried out. Erroneous conclusions regarding the
      reason for different tick numbers between the breeds could result in farmers
      being incorrectly encouraged to utilize smaller breeds to obtain 'built-in'
      resistance to A. hebraeum ticks. One logical explanation for the size-related
      effect is that the males typically attach themselves around the belly and groin
      areas. Larger breeds of cattle, such as the Brahman, will naturally have larger
      surface areas of skin in the belly and groin regions than smaller breeds. Thus,
      it is suggested that there may be a simple physical explanation for the
      difference between breeds in the numbers of attached adult A. hebraeum males.

PMID- 9017877
TI  - Prevalence of Cryptosporidium and Giardia infections in cattle in Aragon
      (northeastern Spain).
AB  - Faecal samples from 554 bovines randomly selected at 30 farms in Aragon were
      examined to investigate the prevalence of Cryptosporidium and Giardia infections.
      C. parvum oocysts were identified by using the Ziehl-Neelsen modified technique
      in 109 (19.7%) bovines ranging from 3 days old to adults. Positive animals were
      found in 19 (63.3%) farms. As much as 44.4% of calves aged 3-4 days were
      infected, but infection rates peaked at 6-15 days of age (76.7%). Nevertheless,
      prevalence was also high in weanling calves aged 1.5-4 months (14%), fattening
      calves and heifers 4-24 months old (7.7%) and adults (17.8%). Diarrhoea was
      recorded in 78.6% of suckling and 29.4% of weanling calves infected by C. parvum,
      but it was only found to be statistically associated with infection in suckling
      calves (P < 0.01). All calves shedding moderate or many oocysts had diarrhoea,
      whereas asymptomatic infection was always correlated with few oocysts in faeces.
      Cryptosporidial infections were always asymptomatic in bovines older than 4
      months. Giardia cysts were identified in 65 bovines (11.7%) from 16 (53.3%) of
      the farms surveyed. Infection rates were significantly higher in suckling (14.1%)
      and weanling calves (38%) than in bovines older than 4 months (2.2%) (P < 0.001).
      Diarrhoea was recorded in 45.5% of suckling and 10.9% of weanling calves infected
      by Giardia, but it was not found to be statistically associated with infection.
      In fact, infection rates were higher in non-diarrhoeic than in diarrhoeic calves.

PMID- 9017878
TI  - B-cell epitope mapping within the MA16 antigenic sequence found in Eimeria
      acervulina merozoites and sporozoites.
AB  - Overlapping heptapeptides derived from the MA16 Eimeria acervulina antigenic
      sequence (Castle et al., 1991) were synthesised on polypropylene pins ('pepskan'
      technique, Cambridge Research Biochemicals, UK). Binding of antibodies from
      chickens and rabbits infected and immunised respectively with various species of
      Eimeria oocysts (E. acervulina, E. tenella, E praecox, E. necatrix and E.
      maxima), was examined using the coated pins as the solid phase of an enzyme
      immunoassay (EIA). Antigenicity of the overlapping synthetic heptapeptides was
      then analysed using a number of algorithms based on the amino acid sequence to
      predict secondary protein structure, hydrophilicity, acrophilicity and chain
      flexibility profiles. The antigenicity of this sequence appears to be quite
      different from that found for the E. tenella GX3264 antigenic sequence (Bhogal et
      al., 1992) whose profile was similarly examined (Talebi and Mulcahy, 1994) using
      the same rabbit and chicken anti-Eimeria oocyst sera.

PMID- 9017879
TI  - Mapping for B-cell epitopes in the GX3262 antigenic sequence derived from Eimeria
      tenella sporulated oocysts.
AB  - Polypropylene pins were impregnated with synthetic overlapping heptapeptides
      based on the GX3262 Eimeria tenella antigenic sequence (Miller et al., 1989).
      Using these coated pins as the solid phase of an enzyme immunoassay (EIA),
      binding of sera from chickens and rabbits infected and immunised respectively
      with five different species of Eimeria were examined. Antibody reactions to the
      individual heptapeptides were then analysed by a number of criteria based on the
      amino acid sequence including hydropathy, chain flexibility and secondary
      structure.

PMID- 9017880
TI  - Antibody and circulating antigen profiles before and after chemotherapy in goats
      infected with Fasciola gigantica.
AB  - The profiles of antibody response and circulating antigen levels in goats
      infected with Fasciola gigantica were studied by enzyme-linked
      immunoelectrotransfer blot (EITB) and enzyme-linked immunosorbent assay (ELISA).
      In the antibody assay, sera from goats experimentally infected with F. gigantica
      were reacted with whole worm antigen of the worm before and after chemotherapy
      with oxyclozanide. In ELISA, there was a significant increase in antibody level 2
      weeks after infection. After chemotherapy, there was a gradual decrease in
      antibody within 3 weeks followed by a rapid decline by the 4th week after
      treatment. By EITB, the infected goat sera recognized three polypeptides in the
      range of 42-80 kDa as early as 2 weeks after infection. Recognition of the
      complete components of F. gigantica antigen repertoire occurred as early as the
      4th week after infection. By the 8th week after chemotherapy, distinct
      polypeptide band recognition was no longer possible. Comparative immunoblotting
      with goat anti-Paramphistomum, anti-Dicrocoelium and anti-Fasciola sera revealed
      that the 14 kDa, 17 kDa, 21 kDa, 28 kDa and 30 kDa proteins are specific to F.
      gigantica. In the antigen assay, circulating antigen was detectable by the direct
      ELISA method one week after infection and negative absorbance values were
      observed 4 weeks after chemotherapy.

PMID- 9017881
TI  - Prophylaxis of bovine trichostrongylidosis and dictyocaulosis in the alpine
      region: comparison of an early and late administration of the oxfendazole pulse
      release bolus to first year grazing calves.
AB  - The effect of the oxfendazole pulse release bolus (OPRB) administered at turnout,
      in May, or in mid-July on the development of infections with gastrointestinal
      nematodes and lungworms in first year grazing calves was investigated with three
      groups of nine animals, all grazing the same pastures in the Swiss midland
      region. In the calves of Group A (OPRB on 21 May) less than 20 eggs per gram of
      faeces (e.p.g.) and less than three Dictyocaulus larvae per 10 g (1.p.10 g) of
      faeces were shed for a period of 126 and 140 days respectively. Towards the end
      of the grazing period calves of this group excreted significantly higher levels
      of lungworm larvae (P < 0.05) compared with the other groups. Prior to OPRB
      administration on 14 July, the calves of Group B developed subclinical infections
      with trichostrongyles and lungworms which were similar to the untreated control
      Group C. By 4 weeks after bolus-administration the excretion of trichostrongylid
      eggs and lungworm larvae declined to levels below 20 e.p.g. and six l.p.10 g
      respectively. Serum pepsinogen values of the calves of Groups A and B were
      significantly lower (P < 0.05) compared with the control animals on days 84 and
      98 after turnout and reflected mainly subclinical infections. With the exception
      of one Group A calf developing clinical parasitic gastroenteritis (p.g.e.) at the
      end of the season, clinical disease was not observed in the treated calves, while
      seven out of nine control animals grazing on the same pastures exhibited clinical
      p.g.e. with mean serum pepsinogen values exceeding 4400 mU tyrosine. Calves of
      Groups A and B gained significantly more weight (P < 0.01) compared with Group C
      (+36 kg and +41 kg respectively); differences between Groups A and B were not
      significant. The results indicate that in mixed grazing systems of treated and
      untreated calves, which are often found in the alpine region, administration of
      the OPRB in May or July provided good results with respect to performance of the
      calves. However, late administration of the OPRB has the additional advantage of
      coverage of the period of higher infection risk with trichostrongyles and
      lungworms in the late season until stabling, and should therefore be recommended.

PMID- 9017882
TI  - Adaptation to arid environment: Haemonchus longistipes in dromedaries of Saharo
      Sahelian areas of Mauritania.
AB  - The adaptations of the trichostrongylid nematode Haemonchus longistipes of
      dromedaries (Camelus dromedarius) to the harsh environment of Saharo-Sahelian
      climate were assessed by means of (i) an epidemiological survey of dromedary
      infection in the south-west of Mauritania, (ii) an estimate over a 3 year period
      of parasite distribution within the host population and of prolificacy of H.
      longistipes females recovered from natural populations of infected dromedaries
      sampled at Nouakchott's slaughterhouse, and (iii) experimental infections of
      young dromedaries during three different periods of the year (end of the rainy
      season, middle and end of the dry season). Egg excretions (estimated by faecal
      egg counts), infective larvae derived from eggs as well as female prolificacy
      showed a marked seasonal pattern: high values in the rainy season and very low
      values in the dry season (especially March and April). Female prolificacy
      differed slightly between morphotypes: the knobbed type excreting over a longer
      period than the linguiform and smooth types. Following experimental infections in
      young dromedaries, arrest of larval development took place irrespective of the
      period. The survival strategy of H. longistipes in the dry season was based only
      on arrested larval development. Patent infections occurred from July to October,
      i.e. during the rainy season and was facilitated by the conjunction of high
      prevalence and intensity of adult worm burdens associated with high female
      prolificacy.

PMID- 9017883
TI  - Identification and characterization of a pyrantel pamoate resistant cyathostome
      population.
AB  - Three fecal egg count reduction assays (FECR) and one critical trial were
      performed to determine the efficacy of pyrantel pamoate (PP) at 6.6 mg base kg-1
      on a well managed stud farm in Louisiana where a loss of efficacy was suspected.
      Efficacy of PP based on FECR varied from 25% in mares to 83% in yearlings. Second
      treatments with PP 2 weeks following an initial treatment failed to reduce eggs
      per gram (EPG). A critical trial was performed to determine the cyathostome
      species resistant to PP. Three strongyle-naive ponies which acquired infections
      on the farm were used for this purpose. Following treatment with PP at the
      recommended dose, 11 species of cyathostomes remained in the intestine of the
      tracer ponies. Reduced efficacies (62%-88%) were noted for seven species.
      Resistance to oxibendazole (OBZ), which was > 90% effective on this farm in 1982,
      was also evaluated by FECR and found to exist. The results of one experiment
      indicate that dual resistance of parasites to PP and OBZ also exists.

PMID- 9017884
TI  - Relationship between genetic diversity in the nematode Trichostrongylus
      colubriformis and breeding management in ten dairy-goat farms.
AB  - Ten dairy-goat farms were investigated in center-west of France for genetic
      variability of Trichostrongylus colubriformis in relation to breeding management.
      Farm management data were obtained from a questionnaire. Genetic variability was
      based on two polymorphic enzymes, malate dehydrogenase (MDH) and glucose
      phosphate isomerase (GPI). After their establishment, the farms were subsequently
      isolated from introduction of strongyle worms as shown in the questionnaire; this
      was also suggested by the absence of a relationship between genetic variability
      and distance between farm locations. The genetic variability which was recorded
      could then be ascribed in part to the influence of management. The breeding
      management estimates combined the fact that animal breeding was the main economic
      resource; that goats were or were not the only animal bred; and that there was or
      was not free access to exercise yards in winter. The farms that were similar on
      the basis of breeding management, were also similar in the frequency of
      allozymes, indicating that the chosen allozymes were not neutral in respect to
      environment. Genetic variability was not related to the frequency of T.
      colubriformis in the strongyle community, this being possibly due to the fact
      that our farm samples predominantly harboured T. colubriformis. Between-farm
      genetic variability was positively correlated to the size of herd (P < 0.01),
      probably due to the fact that larger herds were originally constituted from
      several different herds.

PMID- 9017885
TI  - The effect of truncated infections with Ostertagia ostertagi on the development
      of acquired resistance in calves.
AB  - The relative contribution of the third (L3), fourth (L4) and adult stages of
      Ostertagia ostertagi to the development of immunity was assessed in calves which
      were either continuously infected during 21 weeks or subjected to infections
      truncated by anthelmintic treatment at the L3 or L4 stage. A fourth group
      remained uninfected (control group). Faecal samples and blood samples were
      collected weekly for faecal egg counts and determination of pepsinogen and
      antibody levels. Only the continuously infected animals showed positive egg
      counts, which fell towards the end of the primary infection period. Pepsinogen
      and antibody levels remained high in the continuously infected group until the
      end of the primary infection period. At that time, they were significantly higher
      compared to the control calves, with intermediate values in the truncated
      infection groups. After the 21 weeks primary infection period all animals were
      dewormed. To evaluate the protection provided by the different immunisation
      protocols, all animals were challenged 1 week later with 156000 Ostertagia L3,
      spread over 12 consecutive days. The marked reduction in egg counts following
      challenge infection indicated a certain degree of immunity in the continuously
      infected calves, which was confirmed at necropsy by the reduced worm burdens, the
      high percentage of inhibited early L4 larvae, the reduced size of the adult worms
      and the higher numbers of mucosal mast cells in this group. Numbers of globule
      leucocytes and eosinophils were not significantly different from the control
      group. Infections truncated by anthelmintic treatment elicited poor development
      of immunity as shown by the egg output after the challenge infection and the
      percentages of arrested larvae and the lengths of adult worms which were
      intermediate to those of the continuously infected calves and control animals.

PMID- 9017886
TI  - Serum protein alterations in canine ehrlichiosis.
AB  - Serum protein electrophoresis was performed in 42 dogs with naturally occurring
      Ehrlichia canis infection and in 15 clinically healthy dogs (control dogs). The
      infected dogs were found to have a significant hypoalbuminaemia,
      hyperglobulinaemia and hypergammaglobulinaemia compared to the control dogs (P <
      0.001). A polyclonal gammopathy was found in all but one of the infected dogs
      which presented a monoclonal gammopathy. alpha-1 globulin was lower while alpha-2
      and beta-2 globulin concentrations were significantly higher in the infected dogs
      (P < 0.0001, P < 0.05 and P < 0.005, respectively). The infected dogs were
      divided into two subgroups according to haematological parameters, defined as
      pancytopenic (n = 13) and non-pancytopenic (n = 29). When compared, the
      pancytopenic group revealed significantly lower concentrations of total protein,
      total globulin and gammaglobulin (P < 0.01, P < 0.05 and P < 0.005 respectively).
      The lower concentrations of the gammaglobulins coupled with the pancytopenia
      suggest that the immune state of the pancytopenic E. canis infected dogs is more
      compromised, and therefore secondary infections should be expected more
      frequently in these dogs.

PMID- 9017887
TI  - Prophylactic treatment of experimental canine babesiosis (Babesia canis) with
      doxycycline.
AB  - Doxycycline provided satisfactory prophylaxis against experimental infection with
      a highly pathogenic strain of Babesia canis. Rectal temperature, parasitaemia,
      packed cell volume and serology were monitored for evaluation of the prophylactic
      effect. Although a daily dose of 5 mg kg-1 of doxycycline did not completely
      prevent clinical disease, symptoms remained moderate and a full recovery was
      obtained within 1 week. At a dose of 20 mg kg-1 day-1 no clinical symptoms were
      observed, but asymptomatic infection could not be ruled out.

PMID- 9017888
TI  - Infectivity of Cryptosporidium muris directly isolated from the murine stomach
      for various laboratory animals.
AB  - Oocysts of Cryptosporidium muris, directly isolated from the stomach of
      experimentally infected laboratory mice were orally inoculated into rats,
      gerbils, guinea pigs, dogs, and rabbits. Weaned rats developed patent C. muris
      infection as evidenced by the endogenous stages in gastric glands and oocyst
      shedding 10-17 days later. No signs of clinical illness or macroscopic findings
      were detected in mice and rats. Laboratory raised suckling rabbits, guinea pigs,
      gerbils and dogs fed C. muris rarely developed patent infections and they were
      considered not a true host for C. muris.

PMID- 9017889
TI  - Effects of antihypertensive therapy on glucose and lipid metabolism.
AB  - Large epidemiological studies demonstrate only moderate reduction in the
      incidence of coronary artery disease by antihypertensive drug treatment. This is
      attributed to the prevalence of multiple risk factors in hypertensive patients
      and to possible adverse metabolic effects of antihypertensive drugs which may
      counteract their ability to reduce the risk of cardiovascular disease. The
      choices for pharmacological blood pressure reduction are divided between five
      classes with similar antihypertensive efficacy but markedly different influence
      on coronary risk factors. Hence, the clinician has to consider the prevalence of
      coexisting coronary risk factors, comorbidity as well as the efficacy, side
      effects, and mechanisms of drug action.

PMID- 9017890
TI  - Autoimmune reactions in patients with silicone breast implants.
AB  - Silicone breast implants have been surgical routine for over 30 years. An
      association between silicone augmentation and immune related diseases has been
      reported in approximately 100 cases. In a retrospective single center study we
      investigated 36 non-selected women with silicone breast implants and 36 sex- and
      age-matched controls. Autoimmune reactions were evaluated by measuring
      antinuclear antibodies (ANA), rheumatoid factor (RF) and thyroid gland antibodies
      (TMS), along with angiotensin-converting enzyme (ACE), C-reactive protein (CRP)
      and other immunological and laboratory parameters. In the controls only 3 (8%)
      women had an elevated ANA titer and 1 demonstrated thyroid autoantibodies
      (microsomal), giving a total of 4 (11%) women with detectable autoantibodies. By
      contrast, 12 (33%) of the 36 women with silicone augmentation had raised ANA
      titers (> or = 1 : 80), a significantly higher percentage than in the control
      group (p < 0.02). Of the 12 women, 1 showed antismooth muscle antibodies (ASMA;
      titer 1 : 40) and 2 of the patients displayed antineutrophilic cytoplasm
      antibodies (ANCA; 1 : 320 and 1 : 40, respectively), one of the latter also being
      positive for rheumatoid factor. 2 further women demonstrated thyroid
      autoantibodies (microsomal), giving a total of 14 (39%) women in whom significant
      autoantibodies were detectable. Clinical symptoms (musculoskeletal) were present
      in 1 patient. Most of the observed autoantibodies were organ-unspecific, with a
      predominance of elevated ANA titers of the heterogeneous type and not related to
      a distinct clinical entity. However, none of the investigated women with silicone
      breast implants showed clinical symptoms or signs of connective tissue disease
      according to ARA criteria.

PMID- 9017891
TI  - Fluid regulation during prolonged physical strain with water and food deprivation
      in healthy, trained men.
AB  - The aim of this study was to investigate fluidregulating mechanisms, with special
      regard to the role of plasma proteins in the control of plasma volume (PV), and
      the role of the superficial tissues as a water storage organ of the body during
      prolonged physical strain. 29 male subjects (mean age 22.2 +/- 2.8 years) were
      studied during a 5 day period of survival training with multifactorial strain
      including restricted water intake (11 H2O.day-1) and food intake (628 kJ.day-1)
      additionally to physical exercise and sleep deprivation (20 h within 5 days).
      Under field conditions the heart rate was monitored continuously, and body mass,
      body composition, thickness of the shell tissues, and blood parameters were
      measured at (T1), after 72 h (T2), after 120 h (T3) and in the recovery period
      after 48 h (T4) and 72 h (T5). The estimated energy expenditure was approximately
      24,000 kJ.day-1. The mean decrease of body mass was 6.77 kg (9.5%) at T3 (p <
      0.001), 0.95 kg (1.3%) at T4 (p < 0.05) and 0.68 kg (0.9%) at T5 (n.s.). A
      reduction of total body water of 3.8 1 was estimated at T3. Serum creatinine
      ([Cr]) was raised at T3 by 18.5% (p < 0.0001). No relationship was found between
      [Cr] and other parameters. The PV decreased by 3.7% (p < 0.0001) at T2, increased
      by 1.6% (p < 0.0001) at T3 and was not different to baseline at T4 (+0.2%; n.s.).
      Total protein concentration ([TP]) increased at T2 (11.7%; p < 0.0001) and T3
      (2.6%; p < 0.01), and decreased (p < 0.0001) at T4 (8.2%) and T5 (5.7%). Plasma
      proteins shifted into the intravascular space at T2 and T3 and moved out of the
      intravascular space at T4 and T5. This gives support to the hypothesis that one
      of the counterregulatory mechanisms maintaining PV during prolonged exercise is
      provided by protein shifts from the extravascular into the intravascular space.
      Our data provide evidence that this mechanism assists PV homeostasis efficiently
      over a period of 120 h with multifactorial strain, even under conditions with a
      fluid loss of almost 8% of the total body water.

PMID- 9017892
TI  - Acupuncture as an adjuvant therapy in stroke rehabilitation?
AB  - The optimal treatment during stroke rehabilitation has not yet been identified.
      Several recent reports claim that acupuncture may be a useful addition to
      conventional stroke rehabilitation. The aim of this paper is to critically review
      these data. All controlled trials published on this subject were identified by
      systematic literature searches. Without exception, these trials suggest positive
      effects of acupuncture on functional recovery. None of them, however, attempted
      to account for a possible placebo effect. Several other methodological flaws must
      be considered as well. It is therefore concluded that, according to the data
      published to date, the evidence that acupuncture is a useful adjunct for stroke
      rehabilitation is encouraging but not compelling. More and better trials are
      required to clarify this highly relevant issue.

PMID- 9017893
TI  - 50 years ago: the Nuremberg Doctors' Tribunal. Part 1: The descent towards
      medicalised murder.
AB  - This series of four parts is an attempt to summarise some aspects of medicine
      during the Third Reich. Its aim is not to provide a systematic review but to
      remind us of this darkest chapter in the history of medicine and its
      consequences. The paper summarises the complex evolution of "race hygiene" during
      the Third Reich and tries to show how politics were medicalised by this idea. On
      the basis of "race hygiene", involuntary sterilisation was a first step followed
      by involuntary euthanasia of (mostly) handicapped psychiatric patients. The know
      how acquired during these activities was used in the "Final Solution". It
      presented a level of medical barbarism only to be exceeded by criminal medical
      research conducted in some concentration camps.

PMID- 9017894
TI  - Ileal inhibition and modulation of carbachol-stimulated proximal small intestinal
      motor functions in humans.
AB  - Carbohydrates within the distal small intestine inhibit endogenously stimulated
      proximal gastrointestinal motor activity and induced an interdigestive-like
      pattern in humans. In order to further investigate the intermediary mechanisms of
      the ileal inhibitory effects, we intubated eight healthy volunteers with an
      oroileal multilumen tube and stimulated small intestinal motility exogenously
      with a continuous intravenous infusion of the cholinergic agonist carbachol.
      Additionally, the ileum was perfused for 15-min intervals with either
      carbohydrates (total load: 18 g) or normal saline as volume control. Ileal
      carbohydrate perfusion inhibited the carbachol-stimulated motility pattern
      significantly (p < 0.001) and induced phase-III-like motor activity; ileal saline
      had no effect. These data suggest that a direct inhibition of cholinergic systems
      may be involved in the ileal inhibitory effects on proximal small intestinal
      motility.

PMID- 9017895
TI  - Transplantation of complete and split liver grafts for patients with fulminant
      hepatic failure.
AB  - Fulminant hepatic failure is associated with considerable mortality under
      conservative management. The aim of this study was to assess applicability and
      outcome of liver transplantation using cadaveric and living donated grafts in
      patients with fulminant hepatic failure. 42 patients presenting with fulminant
      hepatic failure between 1988 and 1995 were retrospectively analyzed. 37 (88%) met
      the indication criteria for liver transplantation. 22 patients underwent
      orthotopic liver transplantation, one patient auxiliary orthotopic liver
      transplantation. Actual survival rate of these patients is 74% alter a mean
      follow-up of 23 (3-68) months. 38% (14/37) of the patients with an indication for
      transplantation did not receive a cadaveric graft due to scarcity of cadaveric
      organs (n = 9), medical contraindications (n = 3) or spontaneous recuperation (n
      = 2). Only 21% (3/14) of these patients survived. Due to unavailability of a
      cadaveric organ four patients, six months to 22 years of age, underwent living
      related liver transplantation as a last possible treatment option. Three of them
      died from cerebral herniation. It is concluded that transplantation of a
      cadaveric graft increased survival rate from 21% to 74% in patients with an
      indication for liver transplantation. Living related liver transplantation as an
      individual rescue therapy had no favourable outcome.

PMID- 9017896
TI  - Dissimilar activation patterns of the carcinogen dimethylhydrazine (DMH) on
      intracellular polyamine metabolism in various organs.
AB  - Weekly administrations of the potent carcinogen 1,2-dimethylhydrazine (DMH)
      predominantly induce carcinoma of the colon by nearly 100% after six months'
      treatment in rats. Polyamines, and especially the key enzyme of polyamine de novo
      synthesis ornithine decarboxylase (ODC) are well-known to play an important role
      in cell growth and tumor carcinogenesis. Male Wistar rats were s. c.-injected
      with a single dose of 20 mg DMH/kg b. wt. and five to eight animals were
      sacrificed 4, 8, 12, 24, 72, 120, 168, and 240 hours after injection of DMH or
      the basic solution, respectively. Additionally, seven animals were simultaneously
      treated with the ODC inhibitor alpha-difluoromethylornithine (DFMO) and
      sacrificed seven days after a single DMH injection. A single s. c.-dosage of the
      colon carcinogen DMH resulted in dissimilar activation patterns of polyamine
      metabolism in the various organs studied: in distal and less pronounced in
      proximal colonic mucosa ODC and putrescine are significantly increased seven days
      after application of DMH and DNA polymerase after ten days; in small intestinal
      mucosa ODC activity is significantly elevated after seven days and especially S
      adenosylmethionine decarboxylase activity is significantly and prolonged
      increased between twelve and 72 hours after DMH injection; while
      spermidine/spermine N1-acetyltransferase activity is significantly elevated in
      liver after 168 and 240 hours, no changes compared to controls are found in the
      pancreas. DFMO treatment completely prevents DMH-induced activation of polyamine
      de novo synthesis and DNA polymerase in colon and small intestine. These data
      prove completely different and -interestingly-late appearing activation patterns
      of DMH on intracellular polyamine metabolism in various organ systems and further
      elucidate the complex metabolic changes following carcinogen treatment.

PMID- 9017897
TI  - J.S. Kennedy (1912-1993): a clear thinker in behavior's confused world.
AB  - This is an account of the scientific life of John Stodart Kennedy, Fellow of the
      Royal Society; Emeritus Professor of Animal Behaviour at Imperial College,
      London; the holder of numerous scientific honors; and known to us all as JSK. He
      was not at heart an entomologist; his principal interest was in the integration
      of animal behavior, but he pursued that interest through a lifetime's study of
      locusts, aphids, and moths, especially in the context of how they integrated
      their flight behavior. Two features marked his science: an obsession with
      accurate, objective quantification of animals' behavioral responses through
      experimentation and a ruthless demolition of anthropomorphic analyses of
      behavioral causes. This biography is both a history of his scientific work and a
      tribute to a hugely admired colleague, research leader, and friend of some 30
      years. The details of Kennedy's life were provided in part by his family, in part
      by the autobiographical notes he wrote for the Royal Society, and in part by his
      surviving colleagues from those early years; the last three decades are based on
      the author's personal knowledge and observation.

PMID- 9017898
TI  - Systematics of mosquito disease vectors (Diptera, Culicidae): impact of molecular
      biology and cladistic analysis.
AB  - The field of medical entomology, by nature of its association with problems of
      human health, has been conservative in its application of molecular and computer
      technologies to systematic research. Recently, however, these methods have opened
      new interpretations for systematics of disease vectors. Medically important
      insects, particularly mosquitoes, are among those more thoroughly described by
      conventional taxonomy, and thereby provide a secure framework for testing
      congruencies with molecular data. In turn, molecular investigations have provided
      a stimulus to vector systematics in the discovery and delineation of cryptic
      species complexes, as well as providing new perspectives on relationships at
      higher taxonomic divisions. In this review, examples involving cladistic
      analysis, cytogenetics--in situ hybridization, isoenzymes, DNA sequencing, and
      restriction fragment polymorphism are drawn from the following taxa: Aedes
      communis; Aedes (Ochlerotatus) group G; Aedes (Stegomyia) species including A.
      aegypti, A. albopictus, and A. scutellaris group; Anopheles albitarsis, Anopheles
      dirus, Anopheles gambiae, Anopheles nuneztovari, Anopheles pseudopunctipennis,
      and Anopheles punctulatus groups; Culex pipiens and the Culex subgenus
      Melanoconion; and the tribe Sabethini.

PMID- 9017899
TI  - The biology, ecology, and management of the cat flea.
AB  - The cat flea, Ctenocephalides felis felis, is the most important ectoparasite of
      domestic cats and dogs worldwide. In addition to its annoyance to pets and
      humans, C. felis felis is responsible for flea bite allergy dermatitis and the
      transmission of dog tapeworm. The abiotic and biotic factors that affect the
      development of immature stages are reviewed with special emphasis given to those
      aspects directly affecting control. Factors influencing host selection and
      feeding by adults are summarized. Recent studies concerning mating and
      oviposition, especially as they impact the likelihood of survival by immatures,
      are discussed. There has been an increase in the number of reports of insecticide
      resistance in the past ten years. Greater attention has been placed on disrupting
      larval development in modern IPM programs. The immature stages of the cat flea
      are extremely susceptible to environmental factors such as temperature and
      relative humidity and insect growth regulators (IGRs). In recent years, the
      control of cat fleas has increasingly relied on the use of IGRs applied to the
      host or to the indoor environment. Finally, we discuss advances in pesticide
      chemistry that provide tools for better control of adult fleas on the host.

PMID- 9017900
TI  - Bionomics of the face fly, Musca autumnalis.
AB  - The face fly was introduced from the Palearctic region and spread across North
      America in 20 years after World War II. Adults feed on cattle and horses, and
      larvae develop in fresh cattle dung. Little genetic differentiation appears
      between European and North American populations and among regions within North
      America. After an autumnally initiated diapause, overwintered flies emerge in
      spring and reproduce through late spring and summer. Generations after the first
      overlap, and age structure develops toward a stable age distribution. After three
      to ten generations, depending on weather, facultative diapause interrupts host
      feeding and oogenesis, and flies with hypertrophied fat body enter overwintering
      hibernaculae. Life table statistics and factors affecting population growth and
      diapause are reviewed. Early views on the fly's effects on animal productivity
      may have been exaggerated. On-farm control by conventional means has not been
      effective because of the fly's population dynamics and mobility. We suggest that
      the alternatives of classical biological control and area-wide control with the
      sterile insect technique should be considered.

PMID- 9017901
TI  - Genetic dissection of sexual behavior in Drosophila melanogaster.
AB  - Mating of Drosophila melanogaster is a sterotypically patterned behavior
      consisting of a fixed sequence of actions that are primarily under genetic
      control. Mutations that disrupt specific aspects of mating activities offer a
      starting point for exploring the molecular machineries underlying sexual
      behavior. Several genes, identified as causing aberrant sexual behavior when
      mutated, have been isolated and cloned, providing molecular probes for expression
      and mosaic analyses that can be used in specifying the cells responsible for the
      behavior. This review presents current understandings of mating behavior obtained
      by such molecular and cellular approaches and provides an overview of future
      directions of research in behavioral genetics.

PMID- 9017902
TI  - Biological mediators of insect immunity.
AB  - Infection in insects stimulates a complex defensive response. Recognition of
      pathogens may be accomplished by plasma or hemocyte b1p4eins that bind
      specifically to bacterial or fungal polysaccharides. Several morphologically
      distinct hemocyte cell types cooperate in the immune response. Hemocytes attach
      to invading organisms and then isolate them by phagocytosis, by trapping them in
      hemocyte aggregates called nodules, or by forming an organized multicellular
      capsule around large parasites. These responses are often accompanied by
      proteolytic activation of the phenoloxidase zymogen that is present in the
      hemolymph. A component of insect immune responses to bacteria is the synthesis by
      fat body and hemocytes of a variety of antibacterial proteins and peptides, which
      are secreted into the hemolymph. These molecules attack bacteria by several
      mechanisms. Inducible antifungal proteins have also been recently discovered in
      insect hemolymph. The promoters for several antibacterial protein genes in
      insects are regulated by transcription factors similar to those involved in
      mammalian acute phase responses.

PMID- 9017903
TI  - [Aeromonas hydrophila rapidly progressive myonecrosis].

PMID- 9017904
TI  - [Antimicrobial treatment: some considerations regarding its economic evaluation].

PMID- 9017905
TI  - Iatrogenic rupture of internal carotid artery aneurysm. A complication of CT
      guided needle biopsy of the neck.
AB  - Incidental rupture of an internal carotid artery aneurysm complicating a CT
      guided needle biopsy of the neck is reported. A contrast CT scan failed to
      diagnose the lesion, which was not pulsatile and thought to be a neoplastic
      cervical lymph node. After leakage of the aneurysm. Color-Doppler scan and MRI
      identified aneurysmal changes of the carotid artery wall with an intraluminal
      thrombus. Successful emergency resection with a PTFE interposition graft was
      performed.

PMID- 9017906
TI  - Localization of cytoskeletal proteins in Cryptosporidium parvum using double
      immunogold labeling.
AB  - Actin and some actin binding proteins such as tropomyosin, alpha-actinin and
      troponin T were localized by simultaneous double immunogold labeling in several
      developmental stages of Cryptosporidium parvum. All of the observed developmental
      stages have many particles of tropomyosin and actin around pellicle and
      cytoplasm. Tropomyosin was labeled much more than the actin when these two
      proteins were labeled simultaneously. And alpha actinin was labeled mostly in the
      pellicle, but troponin T labeling was very rarely observed. From this study, it
      was suggested that tropomyosin seemed to be one of the major proteins of C.
      parvum, so it must be playing important roles in C. parvum.

PMID- 9017907
TI  - [A survey of canine heartworm infections among German shepherds in South Korea].
AB  - A survey of canine heartworm (Dirofilaria immitis) infections among German
      shepherds in five areas of South Korea was performed from October 1994 to August
      1995 using a microfilarial test (modified Knott's test) and an antigen test
      (DiroCHEK, Synbiotics, USA). The infection rate of 127 German shepherds (71 males
      and 56 females) was 10.2% (13/127) by the microfilarial test, but was 28.3%
      (36/127) by the antigen test, revealing that 24 of the 36 antigen-positive dogs
      were microfilaria negative in the peripheral blood. All dogs that were
      microfilaria-positive were also antigen positive. There of the microfilaria
      negative and antigen positive dogs contained 4.15 adult heartworms in the heart
      and pulmonary arteries upon necropsy. The infection rate among German shepherds
      was the highest in Hoengsong-gun (Kangwon-do, 84.4%), while those of Yechon gun
      (Kyongsangbuk-do) and Chungwon-gun (Chungchongbuk-do) areas were 20.0% and 14.3%,
      respectively. None of the dogs in the Kimhae-shi (Kyongsangnam-do) and Kwangju
      areas was heartworm positive. The infection rates of heartworm in dogs at the age
      of 1-3, 4-6, and 7-11 years were 6.2%, 21.4%, and 56.4%, respectively. Based on
      the fact that the antigen test is more accurate than the microfilarial test, this
      study strongly indicates that the prevalence rate of canine heartworm in Korea
      may be higher than previously reported (3.1 approximately 23.0%) which utilized
      microfilarial tests.

PMID- 9017908
TI  - Toxoplasma antibody titers by ELISA and indirect latex agglutination test in
      pregnant women.
AB  - The seroepidemiologic studies on anti-Toxoplasma antibody titers were carried out
      using ELISA and indirect latex agglutination test. Among 899 sera prepared from
      pregnant women, 39 cases (4.3%) revealed positive reaction and 218 sera from
      middle school students showed 4 positive reaction (1.8%) by ELISA. By LAT (newly
      established by National Veterinary Research Institute. Korea), the sera of 7
      pregnant women (0.8%) showed positive reaction. When 80 sera showing > or = 1:8
      by LAT were used for comparing the results obtained from LAT and Toxotest-MT
      (Eiken Chemical Co., Japan), 7 cases and 8 sera were positive, respectively. All
      of 11 sera of proven toxoplasmosis patients showed positive reaction in both
      tests. Overall proportion of agreement between LAT kit and Toxotest-MT was 0.94
      (kappa-index = 0.632, p < 0.011, and LAT was considered to be useful for the
      screening of toxoplasmosis.

PMID- 9017909
TI  - Glutamate dehydrogenase antigen detection in Plasmodium falciparum infections.
AB  - The usefulness of malaria diagnosis by Plasmodium falciparum GDH (NADP+),
      obtained by affinity chromatography, is demonstrated in ELISA assays, testing IgG
      antibodies against GDH (NADP+) from patients with acute malaria, who have had two
      or more episodes of malaria, or from sera of hyperimmune patients. GDH (NADP+)
      thermal stability was demonstrated in a high heat resistance assay. The
      immunofluorescence assay demonstrated that anti-culture (P. falciparum)
      supernatant serum and anti-GDH (NADP+) of Proteus spp. recognized epitopes in
      Venezuelan isolates, and Colombian and Brasilian malarial strains. The antigen is
      soluble, with high specificity, is a potent immunogen and is thermoresistant.

PMID- 9017910
TI  - Differentiation of Entamoeba histolytica and Entamoeba dispar in cyst-passers by
      immunoblot.
AB  - Differentiation of invasive strains of Entamoeba histolytica according to their
      pathogenicity has been a topic of long debate, but now the pathogenic species
      only is regarded as E. histolytica while the non pathogenic species is E. dispar.
      The present study applied immunoblot to differentiate infections of the two
      species among microscopically-detected cyst-passers in Korea. The crude extract
      of E. histolytica separated in 5.20% gradient gels, revealed many fractions of
      94, 81, 71, 50, 44, 38.5, 37.5, 29, 19, and 18 kDa when the cysteine proteinase
      inhibitor, E64, was supplemented. The scrum IgG antibody of 3 proven E,
      histolytica cases reacted with the antigenic fractions of 117, 110, 99, 68, 66,
      60, 54, 52, 46, and 45 kDa. Sera of PCR confirmed 3 cases of E. dispar reacted
      only to the 117 kDa fraction of the E. histolytica crude extract which was
      regarded as non-specific. To the antigen of monoxenic E. dispar, sera of E.
      dispar and E. histolytica cases showed the same immunoblot reactions. The serum
      IgA antibody reacted with several antigenic fractions of both E. histolytica and
      E. dispar, but IgM and IgE antibodies showed no reaction to either antigen. Sera
      of 24 symptomless amebic cyst passers were screened with the E. histolytica
      antigen; two were found to be infected by E. histolytica and 22 were by E.
      dispar. The present findings suggest that in Korea most of asymptomatic cyst
      passers of E. histolytica are carriers of E. dispar. Immunoblot using E.
      histolytica antigen is a good technique for the differentiation of E. histolytica
      and E. dispar infections.

PMID- 9017911
TI  - Chronologic change of serum IgG antibody response in chickens reinfected with
      Cryptosporidium baileyi.
AB  - Eight 2-day-old SPF chickens were each inoculated orally with a single dose of 5
      x 10(5) oocysts of Cryptosporidium baileyi, and immunoglobulin G (IgG) antibody
      responses were chronologically measured by indirect immunofluorescent antibody
      (IFA) assay. Anti-C. baileyi IgG antibody levels remained high (1:106.67 to
      1:512.00) for at least 4 months with 330 days of a detectable period. Ten days
      after the negative conversion, each chicken was re-challenged with 1 x 10(7)
      oocysts of the same species. Subsequent infection in 340-day-old individuals
      caused sudden elevated IgG antibody levels and the titer peaked on day 28
      postchallenge inoculation (PCI), at 1:1.024 with a 65 days of detection period.
      Chickens in primary infection showed oocyst shedding profiles, but did not
      exhibit any oocyst shedding before or after experimental reinfection.

PMID- 9017912
TI  - Close relatedness of Acanthamoeba pustulosa with Acanthamoeba palestinensis based
      on isoenzyme profiles and rDNA PCR-RFLP patterns.
AB  - The taxonomic validity of morphological group III Acanthamoeba spp. is uncertain.
      In the present study, six type strains of group III Acanthamoeba spp., A.
      culbertsoni, A. healyi, A. pustulosa, A. palestinensis, A. royreba and A.
      lenticulata were subjected for the evaluation of their taxonomic validity by
      comparison of the isoenzyme patterns by isoelectic focusing on polyacrylamide
      gels, mitochondrial DNA (Mt DNA) restriction fragment length polymorphism (RFLP),
      and small subunit ribosomal DNA (ssu rDNA) PCR-RFLP patterns. The Mt DNA RFLP
      patterns were heterogeneous between the species. The type strains of A.
      palestinensis and A. pustulosa showed almost identical patterns of isoenzymes and
      rDNA PCR RFLP with an estimated sequence divergence of 2.6%. The other species
      showed heterogeneous patterns of isoenzymes and rDNA PCR-RFLP. It is likely that
      A. pustulosa is closely related with A. palestinensis and that the former may be
      regarded as a junior synonym of the latter.

PMID- 9017913
TI  - A case report of Cheyletiella infestation on a Whippet dog in Korea.
AB  - A clinical case of Cheyletiella infestation on a dog born and raised in Korea is
      reported. A three-year old female Whippet was hospitalized due to a multiple
      fracture and displacement of the left scapula caused by a recent car accident.
      The mite infestation was not noticed at the time of hospitalization. The dog
      underwent multiple operations involving internal fixation of the fractured
      scapula with wire and a plate, followed by extensive chemotherapy with
      antibiotics and prednisolone. After two months of hospitalization, a pruritic
      dermatitis near the left scapula developed. Multiple white dandruff-like flakes
      were seen on the hair coat, especially over the dorsal spine and neck, and the
      dog expressed increased pruritus by frequently licking and scratching the
      affected areas. Local dense accumulations of skin debris that became crusty were
      also observed. Microscopic examination of a skin scraping revealed a heavy
      infestation of cheyletiella yasguri, as identified by the presence of hoks of the
      palpi and the heart-shaped sensory organ on genu I. Immunosuppression elicited by
      the extensive administration of prednisolone was suspected for the initiation of
      the generalized mite infestation.

PMID- 9017914
TI  - [Infection status of Tapes philippinarum collected from southern coastal areas of
      Korea with Parvatrema spp. (Digenea:Gymnophallidae) metacercariae].
AB  - An epidemiologic survey along the several sites of southern coastal areas of
      Korean peninsula was performed to know the infection status of Parvatrema spp.
      metacercariae in Tapes philippinarum. The clams were purchased from 13 coastal
      areas in Kyongsangnam-do and Chollanam-do, in September, 1990. Each of them was
      digested with pepsin-HCl solution and examined under a stereomicroscope for the
      recovery of metacercariae. A total of 232 (77.3%) out of 300 examined clams were
      proved to have 1 to 273 Parvatrema spp. metacercariae (54.7 in average). None of
      the clams from Samsan-myon Kosong-gun and Dolsan-up. Yochon-gun was infected with
      metacercariae. However, all of the clams from Yonghyon-myon, Sachon-gun, Dohwa
      myon, Kohung-gun, Ahllyang-myon, Changhung-gun and Chiryang-myon. Kangjin gun
      were infected with average 71, 31, 80 and 42 metacercariae respectively. Of the
      clams from Kohyon-myon. Namhae-gun. Doam-myon, Kangjin-gun and Kusan-myon,
      Uichang-gun examined, 97.5%, 95.0% and 90.0% were infected with about 117, 76 and
      28 metacercariae. In other 4 surveyed areas. Seolchon-myon, Namhae-gun. Hwayang
      myon, Yochon-gun, Byollyang-myon, Sungju-gun and Bukpyong-myon. Haenam-gun, 55.0%
      80.0% of clams were positive, and their average intensity of infection ranged
      from 6 to 25 metacercariae. From thse results, it was confirmed that Tapes
      philippinarum from southern coastal areas of Korea are highly infected by
      Parvatrema spp. metacercariae.

PMID- 9017915
TI  - A carbohydrate antigen of Clonorchis sinensis recognized by a species-specific
      monoclonal antibody.
AB  - The enzyme-linked immunosorbent assay (ELISA)-inhibition test using a Clonorchis
      sinensis species-specific mouse monoclonal antibody (MAb), CsHyb 0605-23, showed
      increased specificity over the conventional ELISA used for serodiagnosis of
      clonorchiasis. To characterize the corresponding antigen further, the MAb was
      tested against polysaccharide, protein and glycolipid fractions obtained from a
      crude extract of C. sinensis adult worms, using chloroform, methanol and phenol
      extractions. Only the polysaccharide fraction was recognized by the MAb among
      those fractions. Mild oxidation of the antigen with sodium periodate showed
      decreased reactivity against the MAb. We concluded that the antigen and antigenic
      determinants recognized by the MAb are carbohydrates.

PMID- 9017916
TI  - Conger myriaster, a new second intermediate host of Heterophyopsis continua
      (Digenea:Heterophyidae).
AB  - Six metacercariae were found from the gill filaments of Conger myriaster
      purchased at Mokpo-shi in Korea on 7 September, 1996. Based on the morphology of
      the excysted specimen, we identified them as metacercariae of Heterophyopsis
      continua. C. myriaster is a new intermediate host of H. continua in the
      literature.

PMID- 9017917
TI  - The Williams syndrome: an Italian collaborative study.
AB  - Williams syndrome (WS) is a multiple congenital anomalies/mental retardation
      syndrome caused by a microdeletion on the long arm of chromoome 7 including the
      elastin gene. Possibly it is a contiguous gene syndrome with autosomal dominant
      transmission. Seventy-seven WS patients from 11 Italian Pediatric-Dysmorphology
      Genetics Units were collected by means of a questionnaire designed to draw a
      comprehensive clinical picture, to define the frequency of different traits and
      associations thereof, to better understand the clinical evolution, to improve the
      prognosis and to ameliorate the follow-up. The most important signs for
      diagnosis, based on their relative frequencies, are: mental retardation with
      characteristic outgoing behaviour and hoarse voice; facial findings like stellate
      iris, periorbital fullness and thick lips; congenital heart disease. The
      frequency of the clinical signs reported in our patients are on the whole
      concordant with those found in the literature; the only significant differences
      concern low stature, hallus valgus, hypoplastic nails, joint contractures and ear
      infections. The multisystemic nature of this syndrome requires a coordinated and
      integrated approach in order to avoid fragmentary interventions.

PMID- 9017918
TI  - [Ethical issues in public health activity with special emphasis on nonclinical
      biomedical study].

PMID- 9017919
TI  - [Cross sectional study of the relationship between bone density to diet and life
      style using ultrasound bone densitometry].
AB  - The relationship between bone density to diet and life style was investigated in
      pre- and postmenopausal women in Kyoto Prefecture in 1994 by a cross-sectional
      study. Bone densities of 453 women aged 30-86 years were measured by ultrasound
      bone densitometry. History of pregnancy and delivery, menstruation, medical
      history, bone and arthral symptoms, life style, food intake frequency, current
      and past intake of dairy products, and physical activity were examined by self
      administered questionnaire. Analysis of covariance and multiple-regression
      analysis were performed to determine the relation between bone density and life
      style adjusted for age and obesity index among 151 premenopausal women (PRE), 244
      postmenopausal but not sedentary (under 65 years of age) women (POST), and 58
      sedentary (older than 65 years of age) women (SED). The results were as follows;
      1) A marked age-related decline in bone density was observed at 45-55 years of
      age. The correlation coefficient between age and bone density was significant at 
      0.65 (p < 0.01). 2) Obesity index and bone density were positively correlated in
      each group. 3) Among the PRE group women, there was no relation between life
      style and bone density. Those who experienced bone fractures tended toward low
      bone density. Among the POST group, time since menopause, exercise, and current
      milk intake were significantly correlated with bone density. In the SED group,
      women with arthralgia showed significantly lower densities. 4) From multiple
      regression analysis, age, obesity index, and milk intake during childhood were
      shown to be related to bone density in each group.

PMID- 9017920
TI  - [Serovars and drug susceptibility of Salmonella isolated in humans from 1987-1993
      in Aichi prefecture].
AB  - Drug susceptibility and serovars for a total of 1,110 strains of Salmonella
      isolated from humans during a period from 1987-1993 in Aichi prefecture were
      studied. The isolates consists of 1,022 strains from healthy individuals and
      patients with sporadic diarrhea, 36 imported strains from overseas travellers,
      and 52 strains from patients involved in 7 food poisoning incidents. The strains
      of the first group were serologically classified into 93 serovars. The
      predominant serovars isolated were S. Enteritidis, S. Litchfield, S. Hadar, S.
      Typhimurium and S. Infantis. In drug susceptibility tests using 8 drugs, the
      frequency of drug resistance and number of patterns of resistant isolates were
      46% and 33 patterns, respectively. There were different resistant rates and
      characteristic resistance patterns in each serovar of the isolates. Some of the
      resistance patterns of isolates derived from food poisonings were rare during the
      year of occurrence. Thus, it seems that surveillance of Salmonella may provide
      valuable fundamental epidemiological data.

PMID- 9017921
TI  - [Survival factors in healthy aging among rural Japanese residents of Aichi].
AB  - To investigate survival factors in healthy aging among rural Japanese elderly
      residents, a nested case-control study was conducted. Subjects who answered
      questionnaires in 1985 were followed for 10 years. Cases comprised 124 men and
      109 women who, in 1995, were 75 years old or over, and whose activities of daily
      living were active enough to cope for themselves. Controls were selected from
      subjects who died between 1987 and 1994. One control per case was randomly
      selected, and matched to each case for sex and birth-year (+/- 2 years). The
      survival odds ratio (sOR) was calculated by using a conditional multiple logistic
      regression model. An sOR greater than 1.0 was observed for frequent intake of
      eggs, regular daily routine, adaptability to changes, leisure time exercise and a
      health examination at least once within 3 years. In both men and women present or
      past history of heart disease, cerebrovascular disease and diabetes, family
      history of hypertension, and in women, smoking were negatively associated with
      survival. By multivariate analysis, adaptability to change in men, and regular
      daily routine and health examinations in women were positively associated to
      survival. Smoking and history of chronic disease were negatively associated with
      survival, in both men and women. In conclusion, it is suggested that
      psychological factors and recent health examinations were positively associated
      to survival in healthy aging, and habitual smoking and chronic disease
      contributed negatively to survival. These results require further careful
      evaluation to determine whether the factors are associated with cause or effect.

PMID- 9017922
TI  - [Role of crisis intervention in psychiatric emergent system--effectiveness of
      home visit by a doctor, consultation by phone and walk-in services in general
      hospitals].

PMID- 9017923
TI  - [Investigation of the actual living conditions of patients with chronic
      neurological and muscle diseases and their families].

PMID- 9017924
TI  - [Accuracy of participation rate data for health examination research].
AB  - Each local government conducts health examinations based on the Health and
      Medical Law for the Aged. However, since some residents are able to take health
      examinations at their own work places, for example, and the local government are
      allowed to exclude such people from taking the law-mandated health examination,
      it is difficult to obtain an accurate picture of the examination rate in each
      area. We investigated the actual participation status for health examination
      services of all of the 6,080 persons 20 years and over in age in Sakuragawa-mura,
      Ibaraki Prefecture. A comparative investigation was made on 3,655 non
      bedridden/non-hospitalized persons of 40 years and over to ascertain the
      reliability of responses to questions about participation in lung cancer and
      gastric cancer examination services given by the village. The rate of valid
      responses was extremely low in those who had not participated in health
      examinations (male 54%, female 55% for the lung cancer, and male 53%, female 56%
      for the gastric cancer). These discrepancies are assumed to be the result of
      confusing the current health examinations with: (1) the health examination given
      in the previous year, (2) other kinds of health examinations, or (3) the health
      examination given in the work place or the like. A comparative investigation
      through logistic regression analysis, between the responses to the questions in
      this investigation and the actual health examination participation records, for
      persons who had not yet taken either lung cancer examinations or gastric cancer
      examinations (908 males and 938 females for the former, and 1,038 males and 1,187
      females for the latter). Results showed that the influence of (1) and (2) were
      more or less detected in every kind of cancer examination, and the influence of
      (1) on the gastric cancer examination was particularly clear. No definite result
      was obtained about (3), because the actual record of the health examination
      service at the work place, etc. was unavailable. The results of this study
      suggests the necessity of a careful examination of methods when conducting a
      comprehensive service investigation for the health examinations.

PMID- 9017925
TI  - Glycoconjugated aroma compounds: occurrence, role and biotechnological
      transformation.
AB  - The present paper reviews the occurrence of glycosidically bound aroma compounds
      in the plant kingdom and discusses different hypotheses concerning their role in
      plants. Emphasis is on biotechnological methods for flavor release and flavor
      enhancement through enzymatic hydrolysis of glycoconjugated aroma substances.

PMID- 9017926
TI  - Prospects for the bioengineering of isoprenoid biosynthesis.
AB  - Over the last decade, our understanding of isoprenoid biosynthesis has progressed
      to the stage where specific strategies for the bioengineering of essential oil
      production can be considered. This review provides a current overview of the
      enzymology and regulation of essential oil isoprenoid biosynthesis. The reaction
      mechanisms of the synthases which produce many of the basic isoprenoid skeletons
      are described in detail. Coverage is also provided of the regulation of
      isoprenoid biosynthesis, including the roles played by tissue and subcellular
      compartmentation, and by partitioning of intermediates between different branches
      of isoprenoid metabolism. This provides necessary context for rationally
      targeting specific enzymes of metabolic pathways for bioengineering essential oil
      production. Wherever possible, emphasis is placed on research specific to
      essential oil isoprenoid biosynthesis, although relevant work related to other
      isoprenoids is also considered when it can provide useful insights. Finally,
      building upon this understanding of essential oil isoprenoid biosynthesis,
      several approaches to the bioengineering of isoprenoid metabolism are considered.

PMID- 9017927
TI  - Special transformation processes using fungal spores and immobilized cells.
AB  - Although many microbial processes have been described which are able to produce
      interesting aroma compounds, the number of industrial applications are limited.
      Reasons for this are in most cases low final product yield, low biotransformation
      rates, substrates and/or end-products inhibition, toxicity towards the
      microorganisms themselves and difficulties of recovery from the bioreaction
      mixture. This means that the development of specific catalysts and processes is
      an important challenge for researchers in this field. This review presents two
      special kinds of catalysts, fungal spores and immobilized cells, with emphasis on
      their production and on their use in the production of aroma compounds. The
      production of fungal spores by solid state fermentation is described in greater
      detail. In the second part, this review also offers examples of development of
      three production processes, the production of methyl ketones of spores of
      Penicillium roquefortii, the hydroxylation of beta-ionone by immobilized
      Aspergillus niger cells, and the production of alkyl pyrazines by bacteria in
      liquid and solid media. For each of these processes, the analysis of limiting
      steps-biological and/or physico-chemical-is presented and the significant role of
      process conditions to increase aroma yield is discussed.

PMID- 9017928
TI  - Prevention of sexual aggression: Sociocultural risk and protective factors.
AB  - Physiological, cognitive, affective, and developmental sociocultural risk factors
      for perpetrating sexual aggression are identified. Feminine and multicultural
      socialization may serve as protective factors against these risk factors because
      both forms of socialization emphasize empathy and sexuality in the context of
      committed relationships. It is proposed that feminist and multicultural education
      across the developmental span may constitute methods of reducing and preventing
      the development of sexually aggressive behavior. However, feminist and
      multicultural approaches may have limited impact without greater acceptance
      within societal power structures, including psychology. The authors call for
      psychologists interested in reducing sexually aggressive behavior to become
      better informed and experienced with feminist and multicultural approaches. They
      also suggest that it may be time for all persons in society to become competent
      in multiple domains.

PMID- 9017929
TI  - Depression and gender. An international review.
AB  - This article reviews and updates major research findings on depressive disorders
      and gender relationships in the United States and abroad. It also considers some
      of the World Health Organization's assessment instruments that may clarify the
      relationship between depression and gender and its cross-cultural ramifications.
      With psychology converging across national boundaries and with gender being a
      variable in psychological research both nationally and internationally, gender
      and its relationship to depressive states is emerging as a focal point of
      interest and concern.

PMID- 9017930
TI  - Reasoning and learning by analogy.
AB  - Analogy is a powerful cognitive mechanism that people use to make inferences and
      learn new abstractions. The history of work on analogy in modern cognitive
      science is sketched, focusing on contributions from cognitive psychology,
      artificial intelligence, and philosophy of science. This review sets the stage
      for the 3 articles that follow in this Science Watch section.

PMID- 9017931
TI  - The analogical mind.
AB  - The use of analogy in human thinking is examined from the perspective of a
      multiconstraint theory, which postulates 3 basic types of constraints:
      similarity, structure, and purpose. The operation of these constraints is
      apparent in laboratory experiments on analogy and in naturalistic settings,
      including politics, psychotherapy, and scientific research. The multiconstraint
      theory has been implemented in detailed computational simulations of the
      analogical human mind.

PMID- 9017932
TI  - Educational implications of analogy. A view from case-based reasoning.
AB  - Case-based reasoning (CBR) focuses on analogy in the context of solving real
      world problems. Its research methodology of computational modeling is aimed at
      deriving hypotheses about cognition. CBR's computational models show the roles of
      encoding, retrieval, and adaptation in analogical reasoning processes. In
      addition, its algorithms provide insight into what it might take to enhance human
      cognition. CBR as a plausible cognitive model can thus advise on educational
      philosophy, educational practice, and design of educational software.

PMID- 9017937
TI  - Association between cellular-telephone calls and motor vehicle collisions.
AB  - BACKGROUND: Because of a belief that the use of cellular telephones while driving
      may cause collisions, several countries have restricted their use in motor
      vehicles, and others are considering such regulations. We used an epidemiologic
      method, the case-crossover design, to study whether using a cellular telephone
      while driving increases the risk of a motor vehicle collision. METHODS: We
      studied 699 drivers who had cellular telephones and who were involved in motor
      vehicle collisions resulting in substantial property damage but no personal
      injury. Each person's cellular-telephone calls on the day of the collision and
      during the previous week were analyzed through the use of detailed billing
      records. RESULTS: A total of 26,798 cellular-telephone calls were made during the
      14-month study period. The risk of a collision when using a cellular telephone
      was four times higher than the risk when a cellular telephone was not being used
      (relative risk, 4.3; 95 percent confidence interval, 3.0 to 6.5). The relative
      risk was similar for drivers who differed in personal characteristics such as age
      and driving experience; calls close to the time of the collision were
      particularly hazardous (relative risk, 4.8 for calls placed within 5 minutes of
      the accident, as compared with 1.3 for calls placed more than 15 minutes before
      the accident; P<0.001); and units that allowed the hands to be free (relative
      risk, 5.9) offered no safety advantage over hand-held units (relative risk, 3.9;
      P not significant). Thirty-nine percent of the drivers called emergency services
      after the collision, suggesting that having a cellular telephone may have had
      advantages in the aftermath of an event. CONCLUSIONS: The use of cellular
      telephones in motor vehicles is associated with a quadrupling of the risk of a
      collision during the brief time interval involving a call. Decisions about
      regulation of such telephones, however, need to take into account the benefits of
      the technology and the role of individual responsibility.

PMID- 9017938
TI  - Treatment of ostial renal-artery stenoses with vascular endoprostheses after
      unsuccessful balloon angioplasty.
AB  - BACKGROUND: Percutaneous transluminal renal angioplasty is a safe and effective
      treatment for nonostial stenoses of the renal arteries, but it has proved to be
      disappointing for ostial stenoses. Therefore, we prospectively studied the use of
      intravascular stents for the treatment of critical ostial stenoses after
      unsuccessful balloon angioplasty. METHODS: Stainless-steel endoprostheses were
      placed across 74 renal-artery stenoses located within 5 mm of the aortic lumen in
      68 patients with hypertension. Twenty patients had mild or severe renal
      dysfunction. The indications for stent placement were elastic recoil (63
      arteries) or dissection (1 artery) of the vessel after angioplasty, or restenosis
      after initially successful balloon angioplasty (10 arteries). Patients were
      followed for a mean of 27 months with measurements of blood pressure and serum
      creatinine, duplex sonography, and intraarterial angiography. RESULTS: Initial
      technical success was achieved in all patients. Minor complications (local
      hematomas) occurred in only three patients; there were no major complications.
      Eighty-four percent of the patients were free of primary occlusion 60 months
      after the procedure. Restenosis of more than 50 percent of the vessel diameter
      occurred in 8 of 74 arteries (11 percent). Reintervention resulted in a secondary
      patency rate of 92 percent. Long-term normalization of blood pressure was
      achieved in 11 patients (16 percent). Serum creatinine levels did not change
      significantly after successful stent implantation in patients with previously
      impaired renal function. CONCLUSIONS: Accurate placement of renal-artery stents
      is technically feasible without major complications. The favorable early and long
      term results suggest that primary stent placement is an effective treatment for
      renal-artery stenosis involving the ostium.

PMID- 9017939
TI  - Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis
      in black Americans.
AB  - BACKGROUND: After the age of 60, isolated cardiac amyloidosis is four times more
      common among blacks than whites in the United States; 3.9 percent of blacks are
      heterozygous for an amyloidogenic allele of the normal serum carrier protein
      transthyretin in which isoleucine is substituted for valine at position 122 (Ile
      122). We hypothesized that the high prevalence of transthyretin Ile 122 is at
      least partially responsible for the increased frequency of senile cardiac
      amyloidosis among blacks. METHODS: Paraffin blocks of cardiac tissue were
      obtained from an earlier study of 52,370 autopsies in Los Angeles and were
      examined by immunohistochemical and DNA analyses. Samples were available from 32
      of 55 blacks and 20 of 78 whites over 60 years of age with isolated cardiac
      amyloidosis and from two control groups (228 cases). RESULTS: Transthyretin
      amyloidosis was identified in 31 of the 32 cardiac-tissue samples from the black
      patients and in 19 of the 20 samples from the white patients. Six of the 26
      analyzable DNA samples (23 percent) from the black patients and none of the 19
      samples from the white patients were heterozygous for the Ile 122 variant. Four
      of 125 DNA samples obtained at autopsy (3.2 percent) from a second, more recent,
      age-matched cohort of blacks without amyloidosis at the same institution were
      heterozygous for the transthyretin Ile 122 allele. On reexamination the cardiac
      tissue from these four patients contained small amounts of amyloid not detected
      at the initial autopsies. All subjects with the Ile 122 variant had ventricular
      amyloid. CONCLUSIONS: The assessment of elderly black patients with unexplained
      heart disease should include a consideration of transthyretin amyloidosis,
      particularly that related to the Ile 122 allele.

PMID- 9017940
TI  - Cerebral microsporidiosis due to Encephalitozoon cuniculi in a patient with human
      immunodeficiency virus infection.

PMID- 9017941
TI  - Images in clinical medicine. Intussusception.

PMID- 9017942
TI  - Racial variation in the use of coronary-revascularization procedures. Are the
      differences real? Do they matter?
AB  - BACKGROUND: Studies have reported that blacks undergo fewer coronary
      revascularization procedures than whites, but it is not clear whether the
      clinical characteristics of the patients account for these differences or whether
      they indicate underuse of the procedures in blacks or overuse in whites. METHODS:
      In a study at Duke University of 12,402 patients (10.3 percent of whom were
      black) with coronary disease, we calculated unadjusted and adjusted rates of
      angioplasty and bypass surgery in blacks and whites after cardiac
      catheterization. We also examined patterns of treatment after stratifying the
      patients according to the severity of disease, angina status, and estimated
      survival benefit due to revascularization. Finally, we compared five-year
      survival rates in blacks and whites. RESULTS: After adjustment for the severity
      of disease and other characteristics, blacks were 13 percent less likely than
      whites to undergo angioplasty and 32 percent less likely to undergo bypass
      surgery. The adjusted black:white odds ratios for receiving these procedures were
      0.87 (95 percent confidence interval, 0.73 to 1.03) and 0.68 (95 percent
      confidence interval, 0.56 to 0.82), respectively. The racial differences in rates
      of bypass surgery persisted among those with severe anginal symptoms (31 percent
      of blacks underwent surgery, vs. 45 percent of whites, P<0.001) and among those
      predicted to have the greatest survival benefit from revascularization (42
      percent vs. 61 percent, P<0.001). Finally, unadjusted and adjusted rates of
      survival for five years were significantly lower in blacks than in whites.
      CONCLUSIONS: Blacks with coronary disease were significantly less likely than
      whites to undergo coronary revascularization, particularly bypass surgery - a
      difference that could not be explained by the clinical features of their disease.
      The differences in treatment were most pronounced among those predicted to
      benefit the most from revascularization. Since these differences also correlated
      with a lower survival rate in blacks, we conclude that coronary revascularization
      appears to be underused in blacks.

PMID- 9017943
TI  - The diagnosis of cystic fibrosis.

PMID- 9017944
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-1997. A 24-year-old woman with cervical lymphadenopathy, fever,
      and leukopenia.

PMID- 9017945
TI  - Cautions about car telephones and collisions.

PMID- 9017946
TI  - Aging, amyloid, and cardiomyopathy.

PMID- 9017948
TI  - Learning to accentuate the positive in managed care.

PMID- 9017947
TI  - Trefoil peptides in the defense of the gastrointestinal tract.

PMID- 9017949
TI  - The effect of universal coverage on health expenditures for the uninsured.
AB  - OBJECTIVES: Universal coverage will trigger an increase in health-care spending,
      because the uninsured will use more services after they are insured. The effect
      of insurance status on expenditures is estimated here from a multivariate
      statistical model. METHODS: The model is estimated with data from the 1987
      National Medical Expenditure Survey, aged to 1994 using population projections
      from the US Bureau of the Census and expenditure projections from the Health Care
      Financing Administration. RESULTS: Expenditures for the full-year uninsured
      increase by approximately $700 per person in 1994 as a result of universal
      coverage. Nearly half of the increase is because of a substantial increase in the
      likelihood of hospitalization. CONCLUSIONS: If the uninsured are enrolled in
      plans similar to those offered by employers currently, personal health-care
      spending increases by approximately $20 billion in 1994. There are other costs
      associated with universal coverage that are not included in this figure.

PMID- 9017950
TI  - Exploring the relationship between inpatient facility and physician services.
AB  - OBJECTIVES: Medicare hospitalizations involve both facility and physician
      services. Although several studies analyze hospital-level variations in Medicare
      inpatient facility and inpatient physician services per admission, few studies
      directly explore the relationship between these services. Theoretically,
      inpatient facility and physician services may be complements or substitutes. That
      is, an increase in facility services may lead to an increase or decrease in
      physician services and vice versa. This article contributes to the existing
      literature by exploring directly the relationship between facility and physician
      services. METHODS: Medicare physician claims were linked to inpatient hospital
      stays using data from the Medicare hospital cost reports, the Medicare Patient
      Analysis and Review file, and the Medicare National Claims History System.
      RESULTS: In multivariate regression analyses, the (partial) correlations between
      facility and physician services were positive, which is consistent with
      complementarity. Standardized regression coefficients indicate that physician
      services are the single most important determinant of facility services; however,
      facility services are a less important determinant of physician services. A 10%
      increase in physician services is associated with at least a 3.0% increase in
      facility services. CONCLUSIONS: Proposals that reduce inpatient physician
      expenditures also would reduce facility expenditures in the long-run.

PMID- 9017951
TI  - Outcomes of acute myocardial infarction in the Department of Veterans Affairs:
      does regionalization of health care work?
AB  - OBJECTIVES: This study examines the association between the regional availability
      of cardiac technology and outcomes of care for patients admitted to Department of
      Veterans Affairs (VA) hospitals. Patients using the VA regional medical system
      initially are admitted to a hospital with or without the on-site availability of
      technology-intensive cardiac services. METHODS: The authors identified male
      veterans (n = 24,229) discharged from VA hospitals with a primary diagnosis of
      acute myocardial infarction (AMI) from January 1, 1988 through December 31, 1990.
      Analyses of mortality up to 2 years after AMI and the use of cardiac procedures
      were stratified by the type of VA hospitals to which patients initially were
      admitted. Logistic regression models adjusted for age, race, marital status,
      hospitalization in previous year, comorbidities, cardiac complications coded, and
      year of AMI. RESULTS: Adjusted mortality was significantly higher for patients
      initially admitted to hospitals without on-site cardiac technology at: 2 days
      (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.62-0.81), 90 days (OR 0.78;
      95% CI 0.73-0.85); 1 year (OR 0.87, 95% CI 0.81-0.93); and 2 years (OR 0.86, 95%
      CI 0.81-0.92) compared with hospitals with on-site cardiac technology (ie,
      coronary angioplasty and cardiac surgery facilities). Patients initially admitted
      to hospitals without on-site cardiac technology also were less likely to undergo
      cardiac procedures than patients admitted to hospitals with on-site cardiac
      technology. CONCLUSIONS: The regional distribution of cardiac technology may
      restrict patient access to technology-intensive services and to "equally good
      medical care." Policies that promote regionalization of medical services should
      consider carefully the distribution of benefits and burdens to patients.

PMID- 9017952
TI  - Medicaid participation among urban primary care physicians.
AB  - OBJECTIVES: This article describes Medicaid participation among office-based
      primary care physicians in cities and examines its determinants. METHODS: Data
      used in this study were collected through the 1993 and 1994 American Medical
      Association Socioeconomic Monitoring System telephone surveys. The sample
      includes 1,300 primary care physicians. Our multivariate model includes a variety
      of personal, practice, community, and policy factors thought to influence
      participation. Logistic regression was used to examine determinants of accepting
      any Medicaid patients and ordinary least square regression was used to examine
      determinants of the extent of participation among participants. RESULTS: The
      authors found that 19% of respondents did not participate in Medicaid and 62% had
      practices with 9% or fewer Medicaid patients. Multivariate analyses indicated
      that Medicaid payment levels were not associated with observed patterns of
      Medicaid participation. Community sociodemographic characteristics and demand
      from Medicaid-eligibles, by contrast, play a significant role in influencing
      observed levels of participation. CONCLUSIONS: Strategies other than raising
      Medicaid payment levels will be needed to achieve equitable access to office
      based primary care for the poor residing in cities.

PMID- 9017953
TI  - Differences in procedure use, in-hospital mortality, and illness severity by
      gender for acute myocardial infarction patients: are answers affected by data
      source and severity measure?
AB  - OBJECTIVES: According to some studies, women with heart disease receive fewer
      procedures and have higher in-hospital death rates than men. These studies vary
      by data source (hospital discharge abstract versus detailed clinical information)
      and severity measurement methods. The authors examined whether evaluations of
      gender differences for acute myocardial infarction patients vary by data source
      and severity measure. METHODS: The authors considered 10 severity measures: four
      using clinical medical record data and six using discharge abstracts (diagnosis
      and procedure codes). The authors studied all 14,083 patients admitted in 1991
      for acute myocardial infarction to 100 hospitals nationwide, examining in
      hospital death and use of coronary angiography, coronary artery bypass graft
      surgery (CABG), and percutaneous transluminal coronary angioplasty (PTCA).
      Logistic regression was used to calculate odds ratios for death and procedure use
      for women compared with men, controlling for age and each of the severity scores.
      RESULTS: After adjusting only for age, women were significantly more likely than
      men to die and less likely to receive CABG and coronary angiography. Severity
      measures provided different assessments of whether women were sicker than men;
      for all cases, clinical data-based MedisGroups rated women's severity compared
      with men's, whereas four code-based severity measures viewed women as sicker.
      After adjusting for severity and age, women were significantly more likely than
      men to die in-hospital and less likely to receive coronary angiography and CABG;
      women and men had relatively equal adjusted odds ratios of receiving PTCA. Odds
      ratios reflecting gender differences in procedure use and death rates were
      similar across severity measures. CONCLUSIONS: Comparisons of severity-adjusted
      in-hospital death rates and invasive procedure use between men and women yielded
      similar findings regardless of data source and severity measure.

PMID- 9017954
TI  - Malpractice, defensive medicine, and obstetric behavior.
AB  - OBJECTIVES: The authors examine 58,441 obstetric deliveries in New York State
      outside New York City to test for the existence of defensive medicine in
      obstetrics. METHODS: The data consist of merged vital statistics and hospital
      discharge records from the New York State Department of Health, together with
      other merged variables. Physician fear of malpractice is proxied by cumulative
      obstetric malpractice suits by county for 1975 through 1986. A generalized probit
      analysis is used. RESULTS: Malpractice exposure is shown to influence slightly
      the use of the electronic fetal monitor (EFM), a major diagnostic tool. Use of
      the EFM is shown to influence the diagnosis of fetal distress; fear of
      malpractice influences this diagnosis both directly and through the EFM. The
      diagnosis of fetal distress significantly affects the choice of cesarean section
      (c-section) as a method of delivery; hence, fear of malpractice influences the
      choice of a c-section both directly and through the diagnosis of fetal distress.
      Failure to include indirect effects via diagnostic procedures and diagnosis would
      result in an underestimate of the effect of fear of malpractice. Of an overall c
      section rate of 27.6% in the data set, fear of malpractice accounts for an
      estimated 6.6 percentage points, of which 4.4 percentage points reflect a direct
      effect, and the remaining 2.2 percentage points reflect the effect of malpractice
      exposure on the use of the EFM and, directly and indirectly, the diagnosis of
      fetal distress. CONCLUSIONS: The results appear to confirm the existence of
      defensive medicine in obstetrics. Whether this is a desirable or undesirable
      effect remains ambiguous, but it is costly.

PMID- 9017955
TI  - The significance of nm23 protein expression in human gastric carcinomas.
AB  - The clinical significance of nm23 protein (nm23) expression was studied in tissue
      samples from 110 patients with primary gastric cancer by immunohistochemical
      staining with the anti-nm23 antibody. Primary carcinomas with either lymph node
      involvement or liver metastasis expressed significantly reduced levels of nm23
      compared to those without metastasis. This relationship was clearer in the more
      differentiated adenocarcinomas than in the poorly differentiated adenocarcinomas.
      However, there was no correlation between nm23 expression and depth of invasion,
      quantity of stroma, infiltrating growth pattern, or macroscopic type. The
      cumulative 5-year survival rates based on nm23 immunoreactivity within the
      primary tumor were significantly higher in the nonreduced expression group (72%)
      than in the reduced expression group (45%). A multivariate analysis revealed that
      nm23 expression levels influence the outcome of patients as strongly as depth of
      invasion and more strongly than the other clinicopathological factors. These
      results suggest that the degree of nm23 expression is closely related to the
      metastatic potential of gastric carcinoma cells and can be used as a prognostic
      indicator independent of the clinicopathological features.

PMID- 9017956
TI  - Immunohistochemical expression of beta-human chorionic gonadotropin in colorectal
      carcinoma.
AB  - The presence of human beta-chorionic gonadotropin (HCG) was immunohistochemically
      studied in 123 cases of primary colorectal carcinoma using the avidin-biotin
      peroxidase complex method. Positive staining for HCG was recognized in 45 (36.6%)
      tumors and a statistical difference was observed between the HCG-positive (n =
      45) and -negative (n = 78) groups concerning the frequency of blood vessel
      invasion in the primary tumor (P < 0.01). The prognosis for patients with HCG
      positive carcinoma was thus significantly worse than that for patients with HCG
      negative carcinoma (P < 0.05). A multivariate analysis using the Cox hazards
      model demonstrated the positive or negative staining of HCG to be one of the
      independent prognostic factors. The above findings show that, in addition to
      various other prognostic factors, the HCG staining status may thus also help in
      determining the prognosis of patients with primary colorectal carcinoma.

PMID- 9017957
TI  - Defecographic assessment after colonic J pouch-anal anastomosis.
AB  - Colonic J pouch anal anastomosis is widely employed after rectal resection. In
      the 36 patients who participated in our retrospective study, although
      postoperative continence was retained/maintained in each individual, a survey
      questionnaire indicated some difficulties in neoanorectal function. Therefore,
      defecography was performed in 20 of these patients. Patients experiencing soiling
      were found to have an increased ano-pouch angle and pelvic floor descent. Loss of
      sensation and incomplete evacuation were also associated with an abnormally large
      pelvic floor descent. However, stool frequency, urgency, and the need for
      medication showed no correlation with any of the defecography parameters. These
      findings thus suggested that the puborectal muscle and the levator ani muscle
      played an important role in postoperative function. Defecography was also found
      to provide a dynamic assessment of the postoperative state of colonanal
      reconstruction.

PMID- 9017958
TI  - Male breast cancer in patients with a familial history of breast cancer.
AB  - We describe herein the clinical characteristics of five male breast carcinoma
      (MBC) patients with a familial history of breast carcinoma (FHBC). Four of these
      patients suffered from multiple primary cancers, being gastric and prostate
      cancer in 1, gastric cancer in 1, and asynchronous bilateral breast cancers in 2.
      The average age of these patients at diagnosis was not lower than that of MBC
      patients with no such familial history. The aggregation of cancer in these
      families had three prominent characteristics: (1) The families included women
      with early-onset breast cancers which had occurred at the ages of 38, 38, and 35
      years, respectively, and/or early-onset uterine cancer which had occurred at the
      age of 35 years. (2) The incidence of multiple primary cancers was significantly
      higher in the siblings of MBC patients with a FHBC than without. (3) There were
      many cancers in hormone-related organs in two families.

PMID- 9017959
TI  - Surgical implication of aortic dissection on long-term outcome in Marfan
      patients.
AB  - We herein review our 17-year surgical experience for the treatment of ascending
      aortic aneurysm in patients with Marfan syndrome to clarify the risks of
      increased mortality and reoperation. The subjects consisted of 15 patients who
      had all undergone surgery for the aortic root and ascending aorta at Niigata
      University Hospital between July 1978 and January 1995. Aortic valve replacement
      and ascending aortic wrapping were performed in 5 patients, Bentall or Cabrol
      operation in 6, and combined aortic arch reconstruction and Cabrol operation in
      2, as the initial surgery. Patients who had an aortic dissection (Stanford type
      A) at initial surgery were assigned to group I (n = 7), while those with an
      aortic root aneurysm were assigned to group II (n = 8). In group I, 3 patients
      required a second operation for the remaining aortic arch aneurysm, and 1 died
      due to a late rupture of the distal aneurysm. In group II, no patient needed a
      reoperation; however, 1 died due to an intracranial hemorrhage and another due to
      composite valve graft failure and distal dissection. The results thus indicate
      that aortic dissection seems to affect long-term outcome, and therefore the
      combined repair of the aortic root and transverse arch is recommended in Marfan
      patients with aortic dissection involving the transverse aortic arch.

PMID- 9017960
TI  - The coagulofibrinolytic state of patients with primary varicose veins of the
      lower legs.
AB  - The relationship between a local hypercoagulable state and primary varicose veins
      of the lower legs was investigated by measuring the plasma levels of D-dimer (DD)
      and the thrombin-antithrombin-III complex (TAT) in 122 consecutive patients
      before treatment, and in 46 patients after surgical intervention and compression
      sclerotherapy. Elevated levels of DD and TAT were found in 25% and 20%,
      respectively, of the 122 patients, being significantly elevated in the patients
      with thrombophlebitis compared to the patients with no dermal symptoms,
      pigmentation, or stasis dermatitis. There was no significant difference in either
      parameter among eight groups of patients classified according to their valvular
      incompetence. The levels of DD and TAT were elevated before treatment in 25% and
      20%, respectively, of 45 treated patients, but became significantly reduced after
      treatment. These results indicate that even though the local hypercoagulable
      state in varicose veins without thrombophlebitis is too subtle to be detected by
      systemic parameters such as DD and TAT, a local hypercoagulable state can be
      detected in a certain proportion of patients with venous stasis by these
      parameters.

PMID- 9017962
TI  - Establishment of a human DAF/HRF20 double transgenic mouse line is not sufficient
      to suppress hyperacute rejection.
AB  - To solve the chronic donor organ shortage, the pig is considered to be a possible
      donor candidate for human transplantation. However, hyperacute rejection occurs
      due to the activation of the complement cascade. Therefore, the introduction of
      human complement inhibitors into animal cells has been proposed as a means to
      prevent such exologous complement activation. To investigate the extent to which
      complement inhibitors are resistant to human sera in discordant animals, we
      established transgenic mice lines which expressed either human decay-accelerating
      factor (DAF) and/or homologous restriction factor 20 (HRF20) using microinjection
      methods. Human sera were injected into (a) 10 control mice, (b) 10 DAF-transgenic
      mice, (c) 10 HRF20-transgenic mice, and (d) 10 DAF and HRF20-transgenic mice. The
      results showed that all the mice in groups a, b, and c died immediately after
      injection. Three of the mice in group d died, while seven survived but showed
      hyperpnea and low activity. The pathological findings of groups a, b, and c
      included severe coagulation; however, the survivors of group d showed less severe
      symptoms. The above findings thus suggest that both DAF and HRF20 tend to prevent
      complement activation to some extent; however, its effectiveness is not
      considered to be sufficient for clinical use in transplantation.

PMID- 9017961
TI  - Use of ultrasound-guided percutaneous needle biopsy in the diagnosis of
      mediastinal tumors.
AB  - We herein report the usefulness of ultrasound-guided percutaneous needle biopsy
      for histological diagnosis in 18 patients with mediastinal tumors. Computed
      tomography revealed these tumors to be in contact with the chest wall. The
      preoperative diagnosis was thymoma in 7 patients, germinoma in 5, neurogenic
      tumor in 3, and "other" in 3. The most commonly encountered indication for an
      ultrasound-guided percutaneous needle biopsy was an anterior mediastinal lesion
      (78%; 14 of 18 patients). In 16 (89%) of the 18 patients, the biopsy diagnosis
      corresponded to the postoperative diagnosis. No complications were encountered in
      any of the patients. This new technique of ultrasound-guided percutaneous needle
      biopsy is both relatively simple and highly accurate and may thus be useful for
      outpatients. Preoperative ultrasound-guided percutaneous needle biopsy is thus
      considered to be a safe and reliable method for the histological diagnosis of
      mediastinal tumors, and a good alternative to traditional biopsy techniques such
      as mediastinoscopy or thoracotomy.

PMID- 9017963
TI  - Effect of a single injection of high-dose FK506 on lung transplantation in rats.
AB  - Orthotopic left lung grafts from Brown Norway (BN) donors were transplanted to
      Lewis (LEW) rat recipients which had been treated with a single dose of FK506
      10mg/kg body weight intramuscularly on postoperative day 3. Although the lungs
      were rejected with a median survival time of 7 days, with a range of 6-8 days in
      the untreated controls, maximum survival was prolonged to 60 days. The major
      adverse effects of this therapy were reduction of feeding, loss of body weight,
      and diarrhea. One of the 7 rats died on the 21st postoperative day due to
      anorexia. The effects of this therapy were investigated by histopathological
      examination and flow cytometric analysis using monoclonal antibodies against rat
      lymphocytes: OX-39 (anti-interleukin 2 receptor (IL-2R)) and OX-6 (anti-class II
      MHC). Histopathologically, the lung allografts showed mild perivascular and
      peribronchiolar cuffs of mononuclear cells, while marked reduction of the thymic
      medulla with FK506 treatment was also observed. Flow cytometric analysis of the
      transplanted lung showed no significant changes. Regarding the thymus, the
      percentages of positive cells labeled with OX-39 and OX-6 were significantly
      suppressed after this treatment. In the spleen, the number of OX-6-positive cells
      significantly decreased. The results using this therapy thus suggest that the
      suppression of IL-2R and MHC class II expression was systemically maintained for
      a long time.

PMID- 9017964
TI  - Adenoid cystic carcinoma of the esophagus: report of a case and review of the
      Japanese literature.
AB  - We report herein the case of a 79-year-old man with adenoid cystic carcinoma
      (ACC) of the esophagus. The tumor had a polypoid appearance and was covered by
      thin esophageal mucosa. As the biopsy specimens suggested a diagnosis of poorly
      differentiated adenocarcinoma, the patient underwent subtotal esophagectomy with
      reconstruction of the gastric tube via the posterior mediastinum. Histologically,
      the carcinoma contained basaloid cells, cribriform foci, and a certain amount of
      eosinophilic hyaline substance. Some of the basaloid cells were stained
      immunohistochemically for keratin, muscle actin, and S-100 protein, a pattern
      which was identical to the pattern of immunoreactivity of the myoepithelium. We
      reviewed 36 other cases of ACC of the esophagus reported in Japan, with special
      reference to the criteria for histological diagnosis.

PMID- 9017965
TI  - Myoepithelial hamartoma of the small bowel: report of a case.
AB  - Benign small bowel tumors seldom cause symptoms, due to the fluid content and
      distensibility of the small bowel. We herein present the case of a solitary ileal
      hamartoma causing melena and abdominal pain in a 24-year-old man. The diagnosis
      of a submucosal ileal tumor was made after performing small bowel barium studies.
      Surgical treatment was undertaken, and a histological examination of the excised
      lesion, which showed a partially ulcerated tumor surface and extended from the
      submucosa to the subserosa, revealed numerous cystic glands of various sizes
      together with bundles of proliferating smooth muscle cells. Histochemical and
      immunohistochemical investigations were performed for differential diagnosis, and
      the tumor features were consistent with a diagnosis of ileal myoepithelial
      hamartoma. In the literature, small intestinal myoepithelial hamartomas are quite
      rare and this is the first report of a myoepithelial hamartoma causing melena.

PMID- 9017966
TI  - Portsite and intraabdominal metastases of unsuspected gallbladder carcinoma after
      laparoscopic cholecystectomy: report of a case.
AB  - We herein report a rare case of portsite metastasis of gallbladder carcinoma
      which occurred after laparoscopic cholecystectomy. A 64-year-old man underwent
      laparoscopic cholecystectomy at another hospital for symptomatic
      cholecystolithiasis. The histological examination revealed an adenocarcinoma of
      the gallbladder infiltrating the entire wall. Despite the physician's advice the
      patient refused any additional treatment. Thirteen months after surgery he
      visited our hospital because of a palpable mass at the scar of the right trocar
      incision. The nodule was removed and histological examination confirmed
      metastasis from the gallbladder carcinoma.

PMID- 9017967
TI  - Tracheal lipoma obstructing the right main bronchus: report of a case.
AB  - Most tracheal tumors are malignant, and benign neoplasms are extremely rare. We
      herein report the case of a 60-year-old woman with a tracheal lipoma obstructing
      the right main bronchus in whom a preoperative diagnosis was not able to be
      established. Thus, a thoracotomy was performed followed by complete resection of
      the tumor including two rings of the tracheal wall. Pathologic examination
      confirmed that the tumor was a lipoma covered with tracheal epithelium, extending
      between the cartilage into the outer layer of the trachea.

PMID- 9017968
TI  - Mesenchymal chondrosarcoma of the rib: report of a case.
AB  - Mesenchymal chondrosarcoma is a rare malignant cartilaginous tumor arising within
      the bone or soft tissue. An 18-year-old woman presented with a tumor on her left
      fourth rib. We performed a wide resection of the tumor and administered three
      cycles of postoperative adjuvant chemotherapy. Three years after the operation,
      the patient is alive without any evidence of either local recurrence or distant
      metastases. The findings of this case may thus support the usefulness of a
      radical resection and adjuvant chemotherapy for mesenchymal chondrosarcoma.

PMID- 9017969
TI  - Fecal incontinence successfully managed by antegrade continence enema in
      children: a report of two cases.
AB  - Two children with intractable fecal incontinence after correction of high
      anorectal malformations were successfully managed by the daily administration of
      a glycerin enema into the cecum via an appendicocecostomy or tubularized
      cecostomy, according to the method of Malone's antegrade continence enema (ACE).
      Fluoroscopic defecography performed during this procedure in each patient
      disclosed that the glycerin enema promptly evoked cecal peristalsis, which was
      transmitted to the distal colon and rectum, and squeezed out almost all the fecal
      matter, evacuating it from the anus. However, two enemas within a short interval
      were required to achieve a complete washout of feces. Although this report
      describes only two patients, our experience confirmed that the ACE was very
      effective and that adding the word "continence" to antegrade enema was
      justifiable. Moreover, fluoroscopic defecography was proven to play a significant
      role in determining the appropriate regimens of this technique to achieve
      complete washout of the feces.

PMID- 9017970
TI  - Functional and biochemical evaluation of the preserved lung in a rat model.
AB  - Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activities and
      total protein concentrations were examined in the postrinsing solutions from rat
      lungs preserved in phosphate-buffered saline (PBS), Euro-Collins (E-C) solution,
      or low-potassium E-C solution for 8 h at 4 degrees C, 10 degrees C, or 20 degrees
      C. The LDH and AST activities were higher when the organs were preserved in PBS
      for 8 h at 20 degrees C than at 4 degrees C or 10 degrees C, while the total
      protein concentration did not differ according to the temperature or solution.
      The activities were also higher when the lungs were preserved in Euro-Collins (E
      C) solution than in PBS or the low-potassium E-C solution. On examining pulmonary
      functions utilizing an ex vivo reperfusion model, the lungs preserved at 20
      degrees C showed poorer gas exchange than those preserved at 4 degrees C or 10
      degrees C. Moreover, the organs preserved in E-C solution showed poorer function
      than those preserved in any other solution. These findings suggest that some
      enzymatic activities in the postrinsing solution could be indicators of lung
      viability after preservation.

PMID- 9017971
TI  - Modification of the stapled functional end-to-end anastomosis for ileostomy
      closure.
AB  - The use of stapling devices simplifies ileostomy closure; however, the original
      functional end-to-end anastomotic technique creates intersecting staple lines,
      generally causing disruption of the anastomosis at the intersections. Therefore,
      we modified the stapling technique to prevent the two staple lines from crossing.
      After the everted ileostomy spout is turned back, a stapled side-to-side
      anastomosis is made. Everting traction sutures are then placed around the
      ileostomy orifice prior to closure with a linear stapler, thus ensuring that this
      staple line does not cross the V-shaped staple line of the intestinal
      anastomosis. This modified technique was employed in the treatment of 20
      patients, none of whom developed any signs of anastomotic leakage or intestinal
      obstruction.

PMID- 9017972
TI  - Trade-off between sibship size and sampling scheme for detecting quantitative
      trait loci.
AB  - There is general consensus that linkage with a quantitative trait locus cannot be
      detected with a reasonable number of sibpairs unless that trait has a very high
      heritability or the pairs are highly selected. However, the latter may require
      the screening of a very large number of pairs before a relatively small number of
      highly informative pairs is attained. At the same time, it is known that, for the
      same number of typed individuals, larger sibships tend to provide more linkage
      information than do independent sibpairs. We thus compared the efficiency of two
      sampling schemes, (1) random and (2) single ascertainment via an individual with
      an extreme phenotype, for sibship sizes ranging from two to five. The results
      demonstrate the clear trade-off between sibship size and the stringency of the
      ascertainment scheme.

PMID- 9017973
TI  - Evidence for an association between the dopamine D3 receptor gene DRD3 and
      schizophrenia.
AB  - Association of the dopamine D3 receptor gene (DRD3) and schizophrenia was
      examined in unrelated Israeli and Italian schizophrenic patients and ethnically
      matched normal control subjects. In the combined sample, there was a significant
      excess of DRD3 allele 2 among the schizophrenic patients (chi2 = 4.70, d.f. 1, p
      = 0.03). Comparison of genotype frequencies revealed an excess of the 2-2
      genotype in the combined schizophrenic sample (chi2 = 8.30, d.f. 1, p = 0.01) and
      in the non-Ashkenazi Israeli schizophrenics alone (chi2 = 5.70, d.f. 2, p =
      0.05). DRD3 2-2 genotype conferred a significantly increased risk of
      schizophrenia (chi2 = 8.21, d.f. 1, p = 0.004; OR = 2.87, CI 95% = 1.36-5.76) in
      the combined sample and in the non-Ashkenazi Israeli schizophrenics (chi2 = 7.22,
      d.f. 1, p = 0.04; OR = 7.22, CI 95% = 1.04-24.83). In the combined and Italian
      samples, allele 2 was associated with early age of onset as was the 2-2 genotype
      in the combined sample and non-Ashkenazi group. The 2-2 genotype was associated
      with poor response to neuroleptics, particularly in the non-Ashkenazi, Israeli
      schizophrenics. The possibility that DRD3 or a locus in linkage disequilibrium
      with it may play a role in the transmission of schizophrenia, is considered in
      relation to previous positive and negative reports.

PMID- 9017974
TI  - Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in
      Brazil.
AB  - Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) variants
      was carried out in 150 unrelated G6PD deficient blood donors from the region of
      Campinas, Brazil. By allele specific oligomer hybridization or digestion of exon
      4 of the G6PD gene with the restriction endonuclease NlaII, we detected the 202 G
      ->A mutation in 146 individuals. This mutation was associated with the 376 G-->A
      substitution and only one haplotype was observed in these individuals. Digestion
      of exon 6 with the restriction enzyme MboII showed the presence of the
      Mediterranean variant in three individuals. Haplotype analysis showed, in all
      three samples, a T at nt 1311 and the C at nt 13 in intron 11, suggesting a
      European origin of this variant. By SSCP analysis and direct sequencing we
      detected the mutation nt 1003 G-->A (335 Ala-->Thr) in one blood donor. This
      mutation was previously described in a boy of Indian ancestry and the variant was
      denominated G6PD Chatam. The case described here has no Indian ancestry; thus, we
      presume that the mutations have arisen independently, although we do not know the
      haplotype of the Indian patient. The haplotype of our case was the most common
      observed in our population (PvuII, BspHI+, PstI+, 1311C, NlaIII-). Thus, our data
      indicate that G6PD A- with the 202 G-->A mutation is the most frequent G6PD
      deficiency in the population of southeastern Brazil. The remaining variants had a
      Mediterranean origin. These results are in agreement with the origin of the
      Brazilian population.

PMID- 9017975
TI  - Distribution of apolipoprotein E gene polymorphisms in Japanese patients with
      Alzheimer's disease and in Japanese centenarians.
AB  - We have demonstrated an association between apolipoprotein E (apoE) gene
      polymorphisms and Alzheimer's disease (AD) in 163 Japanese patients by means of
      PCR. We found a significant increase in risk of nonfamilial AD for apoE allele
      epsilon4 in these individuals; this trend decreases with the increase in onset
      age. In centenarians, the distribution of apoE gene alleles is similar to that in
      the general population. The protective effect of allele epsilon2 against the
      development of AD is not statistically significant in our analysis. This
      indicates that apoE polymorphism is associated with AD regardless of race and
      that the age of onset is related to the apoE gene in the development of AD.

PMID- 9017976
TI  - Haptoglobin phenotypes and gene frequencies in bipolar disorder: an association
      study in family-history subgroups.
AB  - Several studies have shown that major depression is accompanied by significantly
      increased plasma levels of positive acute-phase proteins such as haptoglobin
      (Hp). A significant higher frequency of the HP*1 allele has recently been
      detected in patients with unipolar major depression. Pursuing the hypothesis that
      certain unipolar and bipolar disorders may be genetically related, this study
      analyzed Hp genotype and allele frequencies in bipolar patients, taking into
      account their family history of major affective disorders. An increase of HP*1
      allele frequency was found in the subgroup of patients with family history of
      exclusively unipolar disorder (70% in patients vs. 38% in controls, chi2 = 8.34,
      p = 0.004). The relative risk for the HP*1 carriers in this subgroup was 3.8
      (chi2 = 7.29, p = 0.007). These results suggest a genetic and etiological
      heterogeneity in the bipolar disorder.

PMID- 9017977
TI  - Congenital anomalies in infants with congenital hypothyroidism: is it a
      coincidental or an associated finding?
AB  - During the period between December 1988 and February 1995, a total of 279,482
      newborn infants were screened in the regional neonatal screening program for
      congenital hypothyroidism (CH) in Riyadh province, Saudi Arabia. Eighty-one
      infants were confirmed to have CH giving an incidence of 1 in 3,450. Variable
      congenital anomalies, other than those of the thyroid gland, were present in 16
      (19.8%). The anomalies most frequently encountered were congenital heart defects
      (7), unclassified multiple congenital anomalies (5) and Down's syndrome (2). The
      results of our study confirm this association, and emphasize the need to search
      for such anomalies in infants born with CH. Nationwide studies, however, on birth
      defects in the general population and those associated with CH are still needed
      to help us understanding the role of local genetic and environmental factors.

PMID- 9017979
TI  - Prevalence of erythrocyte pyruvate kinase deficiency and normal values of enzyme
      in a Turkish population.
AB  - A pyruvate kinase deficiency prevalence study and determination of the normal
      levels of the enzyme were performed in Antalya city, Turkey. Heparinized blood
      samples obtained from a representative population of the Antalya province (617
      women and 573 men) were tested for pyruvate kinase deficiency by qualitative and
      quantitative tests between April 1992 and March 1994. The mean pyruvate kinase
      activity was found to be 19.8 +/- 4.0 IU/g Hb whereas the enzyme activity of
      deficient cases varied between 7.5 and 12.2 IU/g Hb. Taking into account that
      pyruvate kinase deficiency is the second most common cause of nonspherocytic
      congenital hemolytic anemia, detection of deficient cases by genetic screening
      tests appears to be an informative clinical indicator of hemolytic anemia.

PMID- 9017978
TI  - Three mutations in the paired homeodomain of PAX3 that cause Waardenburg syndrome
      type 1.
AB  - Genomic DNA from probands of various Waardenburg syndrome (WS) families were PCR
      amplified using primers flanking the 8 exons of PAX3. The PCR fragments were
      screened for sequence variants, and subsequently cycle sequenced. Mutations were
      detected in exon 6 for 3 probands of WS type 1 families. These mutations all
      occur in the paired homeodomain DNA-binding motif.

PMID- 9017980
TI  - A simple and rapid nonisotopic method for sizing CAG repeats in the SCA1 gene.
AB  - Spinocerebellar ataxia type 1 is caused by the expansion of a CAG trinucleotide
      repeat, located at the 5' end of the gene responsible for the disease (SCA1
      gene). We propose a simple and rapid method for SCA1 diagnosis, avoiding both
      radioactive and Southern blotting analysis. The method allows an accurate allele
      sizing by visualization of polymerase chain reaction products through a silver
      nitrate-stained polyacrylamide gel.

PMID- 9017981
TI  - Identification of polymorphisms in the p53 gene by denaturing gradient gel blots.
AB  - Polymorphisms in the tumor suppressor gene p53 were identified by Southern blots
      of denaturing gradient gels (melting polymorphisms). Five polymorphisms were
      identified in white blood cell DNA, with the frequency of heterozygotes varying
      from 4 to 27%. The strategy of hybridizing the same blots with different probes
      suggests that two of the polymorphisms are located in the region of exons 5-6 and
      one is in the region of exons 7-9. This study illustrates the use of this method
      for analysis of tumor suppressor genes and suggests future applications, such as
      for the assay of loss of heterozygosity. That assay is used to detect gene
      deletions in tumors, an important event in human tumorigenesis.

PMID- 9017982
TI  - CA repeat polymorphism of the neuronal nitric oxide synthase gene.
AB  - CA repeat polymorphism in the neuronal nitric oxide synthase gene was studied by
      the polymerase chain reaction. The distribution of allele frequencies in Japanese
      subjects was determined.

PMID- 9017983
TI  - Parental HLA genes, hormone levels and offspring sex ratios.

PMID- 9017984
TI  - Immunohistochemical studies of vascular volume and proliferative activity in
      squamous cell carcinoma of the esophagus.
AB  - For immunohistochemical investigation and clarification of the relationship
      between the vascular volume in esophageal carcinoma and the proliferative
      activity of its tumor cells, we examined surgical specimens of squamous cell
      carcinoma (SCC) of the esophagus from 15 patients. The vascular volume was
      evaluated by immunostaining for platelet-endothelial cell adhesion molecule-1
      with monoclonal antibody JC70, and the proliferative activity of the carcinoma
      cells was evaluated by immunostaining for proliferating cell nuclear antigen
      (PCNA) with antibody 19A2. The ratio of the vascular area to the tumor area and
      the labeling index (LI) for PCNA in the carcinoma cells was then calculated. The
      antibody JC70 was useful for immunohistochemically detecting blood microvessels
      in esophageal carcinoma. The vascular volume, expressed as the ratio mentioned
      above, was higher in well- and moderately differentiated SCCs than in poorly
      differentiated SCC (P < 0.01), and the PCNA LI did not depend on the degree of
      differentiation. However, there was a significantly inverse relationship between
      the ratio of the vascular area to that of carcinoma and the PCNA LI of the
      carcinoma cells (P < 0.01). These findings show that angiogenesis is greater in
      esophageal carcinomas with little proliferative activity.

PMID- 9017985
TI  - Postoperative delirium following gastrointestinal surgery in elderly patients.
AB  - Postoperative delirium is a common complication which can interfere with the
      surgical treatment and recovery of elderly patients, and is likely to prolong
      their hospitalization. Unfortunately, there is as yet no completely effective pre
      and/or post operative technique of patient care to reduce or prevent
      postoperative delirium. In this study, 36 patients aged over 70 years undergoing
      gastrointestinal operations were assessed to examine the relationships between
      the preoperative cognitive state, the postoperative sleep cycle, and the
      occurrence of postoperative delirium. All patients were evaluated preoperatively
      using the revised version of Hasegawa's dementia scale (HDS-R). We correlated
      those test results and assessed the sleep-wakefulness disturbance
      postoperatively, to obtain a clinical DMS-III diagnosis of postoperative
      delirium. The incidence of postoperative delirium was 17% (6/36). The patients
      who developed postoperative delirium demonstrated preoperative cognitive
      impairment, and had a short sleep period during the night and a long sleep period
      during the day. Postoperatively, these results suggest that HDS-R is a useful
      method of evaluating preoperative cognition in elderly patients. Considering that
      sleep deficiency is likely to predispose elderly patients to postoperative
      delirium, techniques to prevent sleep deprivation may be of considerable value in
      minimizing the incidence of postoperative delirium.

PMID- 9017986
TI  - Carcinoids of the rectum: an evaluation of 1271 reported cases.
AB  - The present study was conducted to evaluate the current status of rectal
      carcinoids from multiple systemic aspects, based on extensive information
      provided by 1271 cases cited in 465 international articles published since 1912.
      Each case report was carefully read, computerized, and analyzed by the gut
      pancreatic endocrinoma analysis system (Niigata Registry). To avoid case
      duplication, cases without individual identification, such as the age and sex of
      the patient, and those with identical clinical and laboratory data and institutes
      of source, were excluded. Where appropriate, selected cases from an overall
      gastrointestinal (GI) series consisting of 4461 cases similarly documented in the
      same Registry were referred to for comparison. The representative characteristics
      of rectal carcinoids consisted of a male preponderance, small-sized tumors of 10
      mm or less at detection, predominant submucosal invasion with a relatively high
      incidence of metastases, a high incidence of hematogenous spread, a predominant
      histology of the B-type growth pattern, a low rate of silver reactivity, the
      infrequent association of carcinoid syndrome, and a relatively high rate of
      mortality within 5 years after removal of the lesions.

PMID- 9017987
TI  - Recovery of portal blood flow after percutaneous transhepatic biliary drainage in
      patients with obstructive jaundice.
AB  - Using an ultrasonic Doppler system, we prospectively studied the changes in
      portal venous flow (PVF) following percutaneous transhepatic biliary drainage
      (PTBD) and evaluated the correlation between PVF and liver function in 10
      patients with obstructive jaundice. The patients were divided into two groups
      according to their rate of decrease in serum bilirubin ("b"). Group A comprised 5
      patients with a "b" of less than -0.1, while group B consisted of 5 patients who
      did not meet this criterion. The mean PVF increased following PTBD (P < 0.01).
      The increase in PVF was due to an increase in the maximum velocity of the portal
      vein (Vmax). The rate of increase in the Vmax in group A was significantly higher
      than that in group B on both the 7th and 14th postdrainage days (P < 0.05). The
      rate of increase in the Vmax correlated significantly with the rate of decrease
      in the serum bilirubin concentration (P < 0.01). Based on the above findings, we
      conclude that measuring the Vmax by Doppler ultrasonography is useful in
      evaluating the liver function in patients with obstructive jaundice.

PMID- 9017988
TI  - Serum Clara cell protein levels in lung cancer patients: an assessment of
      preoperative values and postoperative changes.
AB  - Serum levels of protein 1 (P1), a Clara cell protein known to have an
      antiinflammatory effect, were studied in 33 patients with lung cancer before
      surgery, and 3, 7, 14, 21 days, and 2 months after surgery. The preoperative P1
      values of the lung cancer patients were compared with those of 66 healthy
      controls matched by sex and age. The postoperative changes in P1 which occurred
      in the lung cancer patients were compared with those in 16 patients who underwent
      laparotomy for gastric or colon cancer. There was no significant difference in
      the P1 values between the lung cancer patients and the healthy controls; however,
      the postoperative P1 values showed a significant decrease 3, 7, (P < 0.001), and
      14 days (P < 0.05) postoperatively, recovering to normal within 2 months after
      surgery. One patient who died of postoperative pneumonia showed decreasing serum
      P1 levels until death. None of the laparotomy patients showed any decrease in P1
      serum levels. Thus, we conclude that: (a) serum P1 levels do not differ between
      lung cancer patients and healthy individuals; (b) serum P1 levels significantly
      decrease in the early postoperative period, but recover within 2 months after
      lung resection; and (c) the postoperative changes that occur in serum P1 levels
      could provide important information about recovery from intraoperative lung
      damage.

PMID- 9017989
TI  - The status of lower-limb amputation in Bangladesh: a 6-year review.
AB  - We conducted a review of 450 single lower-limb amputations performed in our
      hospital in Bangladesh between July 1982 and June 1987. The incidence of
      amputation in the specific area of 1000000 inhabitants covered by the hospital
      was 0.75/10(3) per year. The indications for amputation were: limb ischemia in
      366 patients (81%), traumatic crush injury in 45 (10%), diabetes-associated
      complications in 20 (5%), severe limb infection in 10 (2%), and neoplasm growth
      in 10 (2%). The ratio of above-knee (AK) to below-knee (BK) amputation was 1:65,
      and 36 patients (8%) required reamputation, 22 of whom had undergone BK
      amputation previously. Thus, the number of patients with a final amputation at AK
      level was 302 (67%). The operative mortality was 21% and the uncomplicated
      primary wound healing rate was 89% within the survivors. Among the 355 patients
      who survived the amputation, 265 (75%) were given a prosthesis, 50 (14%) refused
      a prosthesis, and the remaining 40 (11%) were unfit for a prosthesis.
      Rehabilitation was successful in 44% of the AK and 86% of the BK amputees. In
      conclusion, when amputation is inevitable, maximum consideration should be given
      to the type of surgery performed to avoid rehabilitation failure.

PMID- 9017990
TI  - Surgical stress and the development of complications in relation to
      polymorphonuclear leukocyte elastase (PMNE) levels.
AB  - This study was conducted to examine the effects of surgical stress on changes in
      polymorphonuclear leukocyte elastase (PMNE) levels, and to evaluate the
      relationship of these changes to the development of postoperative complication. A
      total of 69 patients who underwent alimentary surgery were subsequently divided
      into three groups: a complicated group, comprised of 25 patients; an
      uncomplicated group with a high blood loss (H) of more than 1000 ml, comprised of
      18 patients; and an uncomplicated group with a low blood loss (L) of less than
      1000 ml, comprised of 26 patients. The changes in the levels of PMNE, fibronectin
      (FN), and antithrombin III (AT III) were compared among these three groups. In
      the uncomplicated H and L groups the PMNE levels rose significantly on
      postoperative day (POD) 1. On POD 3, high levels of PMNE were still evident in
      the uncomplicated H group, but a decline was observed in the uncomplicated L
      group. From POD 7 onwards the levels decreased to the preoperative values in both
      uncomplicated groups; however, the complicated group continued to show high
      levels even on POD 14. Significantly decreased FN levels were observed for the
      first 3 PODs in each group. The uncomplicated H and L groups regained their
      preoperative levels on PODs 7 and 14, respectively, but no recovery was found in
      the complicated group. The AT III levels showed similar changes to the FN levels
      in all groups. These findings indicate that monitoring the PMNE levels could be a
      useful index for the early detection of postoperative complications following
      alimentary surgery.

PMID- 9017991
TI  - Protective effect of the intravenous administration of ursodeoxycholic acid
      against endotoxemia in rats with obstructive jaundice.
AB  - This study was undertaken to elucidate the effect of the intravenous
      administration of ursodeoxycholic acid (UDCA) on endotoxemia in rats with
      obstructive jaundice from the viewpoint of the biliary excretion of
      lipopolysaccharide (LPS) through hepatocytes. In rats with obstructive jaundice,
      fluorescein isothiocyanate-labeled LPS was administered via the portal vein and
      then its biliary excretion was examined. A significant increase in the LPS
      excretion was thus noticed in UDCA-treated rats at a dose of 0.1 micromol/100 g
      body wt. per min. In place of UDCA, sodium taurocholate at the same dose also
      enhanced the biliary excretion of LPS. Secondly, we also examined whether or not
      UDCA protects against endotoxemia. In this experiment, nonlabeled LPS was
      administered via the portal vein and its peripheral concentration was then
      measured. In UDCA-treated rats, the endotoxin concentration was significantly
      lower. Finally, to elucidate the effect of UDCA on Kupffer cells, serum tumor
      necrosis factor (TNF-alpha) was measured. But UDCA had no effect on the TNF-alpha
      level. These findings thus demonstrate that the intravenous administration of
      UDCA protects against endotoxemia by enhancing the transport of LPS across the
      hepatocytes from blood to bile without affecting Kupffer cells, and that this
      biliary excretion of LPS is dependent on bile acids.

PMID- 9017992
TI  - Simple hemorrhage induces tissue factor mRNA in the liver.
AB  - Thrombogenic responses are sometimes seen after a large hemorrhage, but the
      precise mechanisms whereby this phenomenon occurs still remain unknown. We
      recently showed that plasminogen activator inhibitor-1 rises after a 20-ml/kg
      hemorrhage in rats and suggested that this change may be one of the contributing
      factors to the thrombogenic responses after a large hemorrhage. In this study, we
      set out to detect the changes on the coagulation side, that is, the changes in
      whole blood clotting time and the mRNA of tissue factor (TF), which is the
      primary initiator of the clotting cascade. The rats were all bled (20 ml/kg) 3
      days after cannulation. The whole blood clotting time was measured by the Lee
      White method. Changes in the TF mRNA were detected in the liver by high
      performance liquid chromatography after reverse transcription and polymerase
      chain reaction using glyceraldehyde 3-phosphate dehydrogenase as an external
      standard. A 20-ml/kg hemorrhage significantly shortened the whole blood clotting
      time and significantly increased the TF mRNA in the liver at 1, 2, and 4h in
      comparison to the nonhemorrhage controls. These results indicate that a simple
      hemorrhage without tissue trauma can induce hypercoagulability and suggest that
      the induction of TF might be involved in this phenomenon.

PMID- 9017993
TI  - Expanded polytetrafluoroethylene grafts for portal vein replacement: use of
      omentum wrap to promote graft healing.
AB  - This study was designed to reexamine the healing process of expanded
      polytetrafluoroethylene (EPTFE) grafts with standard porosity (30 microm) and
      high porosity (60 microm) in portal vein replacement, and to evaluate the effect
      of an omentum wrap, which has certain functions that promote healing, on graft
      healing. These grafts, either wrapped by the omentum or not, were placed as
      portal vein replacements in 24 mongrel dogs. After 1 month, the grafts were
      retrieved and examined for patency, thrombus-free areas, thickness of the
      pseudointima, and the total number of cells growing into the graft wall. There
      were no statistical differences in the patency rates. The high-porosity grafts
      had a significantly larger thrombus-free area, a thicker pseudointima, and a
      larger growth of cells than the standard-porosity grafts. The omentum wrap
      significantly increased the thrombus-free area and stimulated a larger growth of
      cells in both grafts. The high-porosity grafts plus omentum demonstrated a
      thrombus-free area of 82.2% vs 27.3% in the standard-porosity grafts. In
      addition, the migration of fibroblasts and macrophages was most evident in the
      high-porosity grafts wrapped by the omentum. In conclusion, graft healing
      enhancement was observed in the high-porosity EPTFE grafts wrapped by the
      omentum. It is thus suggested that transmural cellular migration plays an
      important role in the process of graft healing.

PMID- 9017994
TI  - Effects of granulocyte colony-stimulating factor on bacterial translocation due
      to burn wound sepsis.
AB  - The presence of certain defects in both cellular and humoral immunity after
      thermal injury has been established. Likewise, the translocation of enteric
      bacteria to the mesenteric lymph nodes and to distant organs has also been
      observed following serious thermal injury. The effects of granulocyte colony
      stimulating factor (G-CSF) on bacterial translocation, the small bowel mucosa,
      and cecal bacterial content were investigated in a rat model of burn wound sepsis
      in which albino Wistar rats were scalded over 30% of their bodies, after which
      the lesions were infected by 1 x 10(8) colony-forming units (cfu) Pseudomonas
      aeruginosa. The control group was treated with 5% dextrose solution
      subcutaneously starting 2 days preburn, while the treatment group received 100
      microg/kg human G-CSF subcutaneously. On the 4th day post burn all animals were
      killed to examine the bowel and culture of the mesenteric lymph nodes (MLN),
      livers, and spleens. No significant differences were observed between the groups
      regarding the cecal bacterial content and small bowel; however, a difference was
      seen in the ratio of translocation in the MLN liver and spleen and quantitative
      MLN cultures. Based on these findings, G-CSF was thus found to be significantly
      effective in reducing bacterial translocation due to burn wound sepsis.

PMID- 9017995
TI  - Cytokine mRNA expression after transient and prolonged hypotension.
AB  - The role of cytokines in hemorrhagic shock remains controversial, with some
      studies showing an elevation of cytokines, whereas others do not. We thus
      analyzed the changes in tumor necrosis factor (TNF) activity and in mRNA of TNF
      alpha, interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) after transient and
      prolonged hypotension. In the transient hypotension group (TH group), chronically
      cannulated rats were bled (20 ml/kg x 3 min) without fluid resuscitation. They
      showed transient hypotension, but their blood pressure (BP) quickly stabilized.
      In the prolonged hypotension group (PH group), the rats were bled and maintained
      at a mean BP of 40 mmHg for 60 min, and then were resuscitated with the shed
      blood and an equal volume of saline over 60 min. The serum TNF activity was
      measured by cytotoxicity against the L929 tumorigenic murine fibroblast.
      Messenger RNA of TNF alpha, IL-1beta, and IL-6 in liver was measured semi
      quantitatively by high-performance liquid chromatography after reverse
      transcription and polymerase chain reaction. The increases in the TNF activity
      were not significant in either of the groups above the prehemorrhage levels,
      whereas mRNA of TNF alpha and IL-1beta showed a transient elevation in the TH
      group and a persistent elevation in the PH group. IL-6 mRNA did not increase
      significantly in the TH group, but did increase in the PH group. These results
      show that a large hemorrhage induces cytokine mRNA in the liver and also show the
      differences in the changes of cytokine mRNA after transient and prolonged
      hypotension.

PMID- 9017996
TI  - Carinal resection and reconstruction for recurrent lung cancer.
AB  - A patient with a recurrent tumor in the trachea adjacent to the right main
      bronchus was treated by surgical resection 19 months after undergoing surgery for
      the primary cancer. The patient had previously undergone right upper lobectomy
      for T1N0M0 stage I squamous cell carcinoma. A carinal resection was performed
      which included 4 rings of the trachea, 2 rings of the right main bronchus, and 1
      ring of the left main bronchus. Reconstruction consisted of an end-to-end
      anastomosis of the trachea and left main bronchus, and an end-to-side anastomosis
      of the right and left main bronchi. The postoperative course was uneventful, and
      at present the patient is healthy 12 months following reoperation.

PMID- 9017997
TI  - Gastric cancer with carcinoma erysipeloides caused by spontaneous thoracic duct
      rupture: report of a case.
AB  - A case of extensive skin metastasis (carcinoma erysipeloides) resulting from
      spontaneous rupture of the metastasized Virchow lymph node in a 53-year-old woman
      is herein reported. Imaging evidence attributing this metastasis to spontaneous
      rupture of the fragile thoracic duct at the supraclavicular fossa is presented.
      The patient, who had already undergone gastric resection more than 6 years
      previously because of advanced gastric cancer, died approximately 4.5 months
      after the occurrence of lymphorrhea in her neck since the anticancer chemotherapy
      administered demonstrated little or no effect.

PMID- 9017998
TI  - Disease-free survival for 6 years and 4 months after dissection of recurrent
      abdominal paraaortic nodes (no. 16) in gastric cancer: report of a case.
AB  - We herein report the case of a 63-year-old woman who underwent curative surgery
      consisting of a subtotal gastrectomy with D2 lymph node dissection for advanced
      stomach cancer in June 1984, and later underwent systemic dissection of recurrent
      abdominal paraaortic lymph nodes by a retromesenteric approach in June 1989.
      Metastatic nodes were found in nos. 16b1 (interaorticocaval), 16b2
      (interaorticocaval), and 280 (aortic carinal). One of the resected nodes, which
      was histologically diagnosed as being poorly differentiated adenocarcinoma,
      measured approximately 10 x 7 cm and infiltrated the inferior caval vein. There
      was no distant metastasis except for nodal metastases. Since the reoperation, the
      patient has been disease-free for 6 years and 4 months, and she continues to
      visit our hospital as an outpatient. The findings of this case therefore suggest
      the significance of paraaortic lymph node dissection. To our knowledge, this is
      the first report in the world of a gastric cancer patient who has remained
      disease-free for more than 5 years after the systemic dissection of recurrent
      paraaortic lymph nodes.

PMID- 9017999
TI  - Successful endoscopic injection sclerotherapy for bleeding from bile duct
      varices.
AB  - A 66-year-old man who had undergone hepatic resection and choledochojejunostomy
      for intrahepatic stones was admitted with dark bloody stools. An endoscopic
      examination failed to detect the origin of bleeding in the esophagus, stomach,
      duodenum, or colon. Angiography showed an obstruction of the main trunk of the
      portal vein and marked cavernous formation of the collateral veins in the
      hepatoduodenal ligament. The patient was finally found to have variceal bleeding
      arising from the common bile duct; this was revealed by an endoscopic examination
      done through a jejunocutaneous fistula created later on. Thereafter, endoscopic
      injection sclerotherapy was successfully used to treat the hemobilia.

PMID- 9018000
TI  - Primary leiomyosarcoma of the thyroid gland.
AB  - Primary leiomyosarcoma of the thyroid gland is extremely rare, and to the best of
      our knowledge only five well-documented cases have been reported in the world
      literature. We herein report a 58-year-old female patient with primary
      leiomyosarcoma of the thyroid who was successfully treated by total thyroidectomy
      with a modified neck dissection. Immunohistochemically, the tumor cells showed
      positive reactivity to alpha-smooth muscle actin and vimentin. Radical surgery
      was thus considered to be essential in the treatment of this rare but rather
      aggressive malignancy.

PMID- 9018001
TI  - Closure of a gastric tube-tracheal fistula by transposition of a pedicled
      sternocleidomastoid muscle flap.
AB  - We treated a 65-year-old man presenting with a gastric tube-tracheal fistula, who
      had undergone subtotal esophagectomy. The radiological and endoscopical findings
      demonstrated a 4-mm gastric tube-tracheal fistula located just above the sternum.
      Conservative treatment using a flexible fiberscope and/or gastrofiberscope,
      including factor XIII with fibrinogen (Beriplast P, Tisseel, and Borheal), alpha
      cyanoacrylate (Aron-alpha-A), n-butyl-2-cyanoacrylate (histoacryl), and human
      antihemolytic factor XIII (Fibrogammin P) in addition to total parenteral
      nutrition with no oral intake did not result in closure of the fistula. The
      fistula was therefore transected and closed through an upper median sternotomy
      and right partial intercostal incision followed by transposition of the
      sternocleidomastoid muscle flap between the gastric tube and trachea. The
      postoperative course was uneventful.

PMID- 9018002
TI  - Assessing the eligibility for liver transplantation of patients with fulminant
      hepatitis.
AB  - The spleen to liver volume (S/L) ratio of 13 patients with fulminant hepatitis
      was determined using X-ray computed tomography (CT), and the correlation between
      S/L ratio and prognosis was evaluated. The S/L ratio of 6 patients who died was
      greater than 0.16, whereas that of the remaining 7 patients who survived was less
      than 0.15. These findings suggest that determining the S/L ratio using CT may be
      useful for assessing the eligibility of patients with fulminant hepatitis for
      liver transplantation.

PMID- 9018003
TI  - Thoracoscopic enucleation of an esophageal leiomyoma with balloon dilator
      assistance.
AB  - In consideration of the fact that procedures performed thoracoscopically cause
      less operative trauma and postoperative pain than those performed through an open
      thoracotomy, we believe that thoracoscopy should replace thoracotomy for the
      extraluminal transthoracic resection of benign esophageal tumors. We describe
      herein a new videothoracoscopic technique for performing the enucleation of an
      esophageal leiomyoma with balloon dilator assistance. The use of the balloon
      dilator facilitates separation of the tumor from both the mucosal and muscular
      layers of the esophagus, and may help to prevent perforation.

PMID- 9018004
TI  - Neurophysiology and neuropsychiatry of the IBS.

PMID- 9018005
TI  - Recovery of cholecystokinin response of porcine gastric chief cells during
      monolayer culture.
AB  - Cell isolation may impair secretory chief cell functions. To evaluate whether a
      monolayer culture results in a recovery, we compared the effects of
      cholecystokinin (CCK) octapeptide (CCK-8) on pepsinogen release from freshly
      isolated and from cultured porcine chief cells. CCK-8 had no significant effect
      on freshly isolated porcine chief cells but stimulated pepsinogen release from 36
      and 60-hour cultured cells with EC50 values of 180 and 130 nmol/l, respectively.
      Maximal stimulation, achieved at a concentration of 1 micromol/l, amounted to 289
      +/- 63 (p <0.01) and 401 +/- 64% (p <0.01) of the respective control value. In
      addition, the CCK-8 concentration-response curve for 60-hour, but not for 36-hour
      cultured chief cells displayed a second stimulatory peak at a CCK-8 concentration
      of 100 pmol/l (266 +/- 55% of control value, p < 0.05) with an EC50 value of 16
      pmol/l. The CCKA-receptor antagonist devazepide (10 nmol/l) prevented the
      stimulatory effect of 1 micromol/l CCK-8 on pepsinogen release of 60-hour
      cultured cells. The adenylate cyclase activator forskolin (10 micromol/l)
      potentiated the low concentration CCK-8 effect, shifting the peak stimulation to
      a CCK-8 concentration of 10 pmol/l, and inhibited the high concentration CCK-8
      effect on 60-hour cultured cells. These results indicate a time-dependent
      recovery of the CCK response of porcine gastric chief cells in monolayer culture
      and suggest that this model has an advantage over freshly isolated chief cells
      with regard to the pharmacological characterization of CCK effects.

PMID- 9018006
TI  - Role of nitric oxide in mucosal blood flow response and the healing of HCl
      induced lesions in the rat stomach.
AB  - The role of nitric oxide (NO) in the gastric mucosal blood flow response and the
      healing of HCl-induced gastric lesions was investigated in rats. After 18 h
      fasting rats were given 0.6 N HCl p.o. for the induction of gastric lesions, and
      1 h later they were fed normally. After induction of gastric lesions, they were
      repeatedly administered the NO synthase inhibitors NG-nitro-L-arginine methyl
      ester (L-NAME 5-20 mg/kg p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once
      daily) for 7 days. Gastric lesions caused by HCl healed almost completely within
      5 days with granulation and to an extent with re-epithelialization. Repeated
      administration of L-NAME but not aminoguanidine significantly delayed the healing
      of gastric lesions in a dose-dependent manner. The damaged mucosa secreted less
      acid, but showed a marked rise in H+ permeability, resulting in luminal acid loss
      accompanied by an increase of mucosal blood flow. Aminoguanidine did not
      significantly affect any of these functional changes observed in the stomach
      after damage by HCl, whereas L-NAME treatment slightly reversed the decreased
      acid response, increased the luminal H+ loss, and totally inhibited the mucosal
      hyperemic response associated with luminal acid loss in the damaged mucosa. In
      addition, the deleterious influences of L-NAME on the mucosal blood flow response
      and the healing of gastric lesions were significantly antagonized by co
      administration of L-arginine but not of D-arginine (500 mg/kg x 2, i.p.). Luminal
      output of NO2-/NO3- was significantly increased in pylorus-ligated stomachs in
      control rats on days 3 and 5 after damage, and such increases in gastric NO
      output were completely attenuated by L-NAME treatment. These results suggest that
      endogenous NO may contribute to the healing of acute gastric injury by mediating
      the mucosal hyperemic responses associated with acid back-diffusion and by
      facilitating acid disposal in the damaged mucosa. NO mediating such responses and
      participating in the healing aspect of gastric lesions may be produced by the
      constitutive type of NO synthase.

PMID- 9018007
TI  - Insulin stimulates production of glycoconjugate layers on the cell surface of
      gastric surface mucous cell line GSM06.
AB  - The mechanism of regulation of mucus production in the gastric mucosa remains
      unclear. Recently, we established a gastric surface mucous cell line GSM06, which
      produces periodic acid-Shiff (PAS)-positive glycoconjugate (mucus) layers on the
      cell surface, from transgenic mice harboring a temperature-sensitive simian virus
      40 large T-antigen gene. In this study, GSM06 cells were examined for its
      production of PAS-positive glycoconjugate layers to acid secretagogues and growth
      factors. The cells were cultured at nonpermissive temperature (39 degrees C) for
      3-18 days and stained with PAS. Insulin (1-30 microg/ml; 0.29-8.6 microM) time-
      and dose-dependently increased production of glycoconjugates on the cell surface.
      When glycoconjugate layers produced by stimulation of insulin (3-30 microg/ml;
      0.86-8.6 microM) were removed from the cell surface of GSM06 cells by a mild
      trypsin treatment, PAS-positive materials were remarkably decreased (day 18). In
      addition, morphological findings indicate that a high concentration of insulin
      (30 microg/ml; 8.6 microM) produced thick PAS-positive glycoconjugate layers just
      like normal gastric surface mucosa on the cell surface on day 18. In contrast,
      histamine (0.1-100 microM), carbachol (0.1-100 microM), gastrin-17 (0.1-100 nM),
      epidermal growth factor (0.01-10 ng/ ml; 1.7-1,700 pM), transforming growth
      factor-alpha (0.01-10 ng/ml; 1.8-1,800 pM), and fetal bovine serum (1-10%) did
      not increase glycoconjugate production. These findings suggest that insulin is a
      stimulator of glycoconjugate production, and stimulates production of
      glycoconjugate layers on the cell surface in the gastric surface mucous cell line
      GSM06.

PMID- 9018008
TI  - Sucralfate impedes intestinal epithelial sheet migration in a Caco-2 cell culture
      model.
AB  - Sucralfate, which binds to the matrix of the ulcer bed, is theoretically
      advantageous for duodenal ulcer therapy, but has not fulfilled its promise
      clinically. We examined the effects of sucralfate and related compounds in a
      human intestinal epithelial (Caco-2) cell culture model of restitution on sheet
      migration across and adhesion to collagen I. Migration was quantitated across a
      collagen I matrix treated with sucralfate or related compounds and correlated
      with cell adhesion. Caco-2 motility was significantly and dose-responsively
      inhibited by sucralfate at therapeutic luminal concentrations. Sucrose
      octaacetate, the sucralfate backbone, and lactose octaacetate exhibited similar
      effects while the beta-bonded disaccharide maltose octaacetate had little effect.
      Sucrose itself slightly stimulated motility. Adhesion effects paralleled
      motility. Thus, sucralfate may inhibit intestinal epithelial motility by
      sterically interfering with adhesion to collagen I. A sucralfate analog with a
      lactose octaacetate backbone might retain growth factor binding without
      inhibiting enterocyte motility, perhaps improving its clinical efficacy.

PMID- 9018009
TI  - Gallbladder motility in response to sham feeding and cholecystokinin in lean and
      obese subjects.
AB  - The risk of developing gallstones is increased in obese subjects. We have
      investigated whether gallbladder motility in obese subjects is different from
      that in lean control subjects. In 25 healthy non-diabetic obese subjects and 20
      age- and sex-matched lean controls, fasting gallbladder volumes, gallbladder
      contraction in response to cephalic vagal cholinergic stimulation by modified
      sham feeding (MSF) and to hormonal stimulation with cholecystokinin (CCK) were
      studied. Gallbladder volumes were measured during a 30-min MSF period followed 1
      h later by a 1-hour continuous i.v. infusion of 0.5 IDU/kg ideal weight of CCK
      33. Fasting gallbladder volumes were significantly (p < 0.001) larger in obese
      (47 +/- 4 cm3) compared to lean subjects (24 +/- 2 cm3). Fasting gallbladder
      volume was correlated with body mass index (p < 0.01). Gallbladder contraction
      during MSF was significantly (p < 0.01) reduced in obese (12 +/- 2%) compared to
      lean subjects (22 +/- 3%). CCK infusion, leading to physiological post-prandial
      plasma CCK levels, induced a significantly (p < 0.001) greater absolute
      gallbladder contraction in obese (27 +/- 3 cm3) compared to lean subjects (15 +/-
      1 cm3) but the percentage gallbladder contraction was in the same range (64 +/-
      3% vs. 67 +/- 4%, respectively). In addition, residual gallbladder volumes after
      CCK infusion were significantly (p < 0.001) larger in obese (15 +/- 2 cm3) than
      in lean subjects (7 +/- 1 cm3). Two groups of obese subjects were identified: one
      with increased (>40 cm3) and one with normal (< or = 40 cm3) fasting gallbladder
      volumes. Only obese subjects with increased fasting volumes showed abnormal
      gallbladder motility.

PMID- 9018010
TI  - Failure of a prolyl 4-hydroxylase inhibitor to alter extracellular matrix
      deposition during experimental pancreatitis.
AB  - In chronic pancreatitis the exocrine pancreatic tissue is replaced by
      extracellular matrix deposits from fibroblasts. We have stimulated fibrogenesis
      in the pancreas by inducing a single episode of cerulein pancreatitis (10
      microg/kg/h for 12 h). We have used a spectrophotometrical assay to measure the
      tissue hydroxyproline content and immunohistochemistry to study the transient
      deposition of extracellular matrix in the pancreas. We have investigated whether
      a potent prolyl 4-hydroxylase inhibitor (HOE-077) can influence the deposition of
      extracellular matrix in the pancreas. Three days after the induction of the
      pancreatitis we found the maximum increase in pancreatic hydroxyproline content
      (by 63%), the maximum decrease in total protein content and amylase activity (by 
      39 and -86%, respectively), as well as a significant increase in DNA content and
      the deposition of interstitial collagen fibers on electron microscopy. By
      immunohistochemistry the largest expansion of extracellular matrix components was
      found for fibronectin. HOE 077, regardless of the concentration administered,
      failed to affect any of these parameters. We conclude that the induction of a
      single episode of cerulein pancreatitis and the serial determination of
      pancreatic hydroxyproline content represents a simple method to induce and
      monitor experimental fibrogenesis in the pancreas. Prolyl 4-hydroxylase
      inhibition did not affect the course of extracellular matrix deposition in the
      pancreas.

PMID- 9018011
TI  - Focal gastric blood perfusion in relation with the endoscopic signs and liver
      function in cirrhotic patients.
AB  - Focal blood perfusion was measured, by means of a laser-Doppler technique, in the
      gastric upper body of 70 patients with liver cirrhosis and of 33 noncirrhotic
      controls. Perfusion was found to be lower in patients with pink mosaic-like
      pattern as compared to controls (p < 0.001). On the contrary, patients with red
      spots showed a marked increase of the focal gastric blood flow (p < 0.001). No
      different blood flow values were found between patients with red mosaic-like
      pattern and controls. Multiple regression showed that focal gastric blood flow
      perfusion was independently related to the Child score (p < 0.003), suggesting
      that gastric hemodynamic abnormalities can be favored by functional
      decompensation of cirrhosis, whereas there was no independent correlation with
      esophageal varices size, as assessed by their lumen occupancy percentage. Such
      observations may contribute to the understanding of the pathophysiology of
      gastric wall lesions in liver cirrhosis

PMID- 9018012
TI  - Alcoholic cirrhosis and cobalamin metabolism.
AB  - The cobalamin status of 27 patients suffering from alcoholic cirrhosis and 20
      control subjects was analyzed. Plasma cobalamin (p < 0.005), total corrinoids (p
      < 0.005) and their analogs (p < 0.05) were all significantly elevated in the
      cirrhosis patients. These differences were due to increased haptocorrin (HC)
      bound corrinoid (p < 0.02), which could be explained by a deficient hepatic
      clearance of cobalamin bound to HC. The increase in the concentration of true
      cobalamin was greater than that of its analogs. There were positive correlations
      between cholestasis (serum alkaline phosphatase) and plasma analog concentrations
      (p < 0.05), HC-bound cobalamin (p < 0.005) and total corrinoids bound to HC (p <
      0.005). The plasma concentrations of the indicators of cobalamin deficiency,
      homocysteine (p < 0.05) and methylmalonic acid (p < 0.001), were increased, which
      could indicate poor cellular penetration of vitamin B12 or a defect in the
      activation of the two vitamin-B12-dependent enzymes.

PMID- 9018013
TI  - Enhanced interleukin-8 production by cultured Chang liver cells subjected to
      ethanol exposure and subsequent stimulation with tumor necrosis factor-alpha.
AB  - We investigated the production of interleukin-8 (IL-8) and chemotactic activity
      released from Chang liver cells subjected to long-term treatment with ethanol
      (Et) and subsequent stimulation with tumor necrosis factor-alpha (TNF-alpha).
      Chang liver cells were cultured in the presence of 5, 50 or 100 mmol/l Et for 4
      weeks and then treated with recombinant TNF-alpha (1, 10, 100 U/ml). The culture
      supernatants were assayed for IL-8 using a sandwich ELISA and chemotactic
      activity was measured using a chemotactic chamber. Total RNA was also extracted
      from these cells and IL-8 mRNA was assayed by RT-PCR. In addition, TNF-receptor
      expression on the Et-treated cells was analyzed by flow cytometry. IL-8 levels in
      supernatants of cells stimulated with 100 U/ml of TNF-alpha for 48 h rose
      significantly with increasing concentrations of Et and values obtained were as
      follows: 4,918 +/- 244.4 pg/ml at 0 mmol/l Et, 5,335 +/- 266.2 pg/ml at 5 mmol/l
      Et, 8,726 +/- 873.4 pg/ml at 50 mmol/l Et and 9,134 +/- 866.0 pg/ml at 100 mmol/l
      Et. The chemotactic activity also increased with increasing concentrations of Et
      and was almost completely suppressed by anti-IL-8 antibody. Using
      semiquantitative analysis of radioactivity of IL-8 mRNA using a 32P gamma ATP
      labeled primer for IL-8 mRNA, Et-treated cells were shown to have markedly higher
      levels of radioactivity than untreated cells. In addition, TNF-receptor
      expression was significantly higher in cells treated with 100 mmol/l Et. These
      data suggest that long-term Et treatment of Chang liver cells stimulated with TNF
      alpha may enhance transcription of the IL-8 gene with up-regulation of the TNF
      receptor.

PMID- 9018014
TI  - Patency of the human accessory pancreatic duct as determined by dye-injection
      endoscopic retrograde pancreatography.
AB  - The accessory pancreatic duct (APD) is the smaller and less constant pancreatic
      duct. The patency of the APD was investigated clinically in an effort to
      determine its role in pancreatic pathophysiology. Dye-injection endoscopic
      retrograde pancreatography (ERP) was performed in 190 cases. In the patients who
      exhibited filling of the fine branches of the ducts on ERP, contrast medium with
      indigo carmine was injected into the major duodenal papilla. The patency of the
      APD was determined by observing the excretion of the dye from the minor duodenal
      papilla. Of the 123 control cases studied, 41% had a patent APD. According to the
      shape of the terminal portion of the APD on accessory pancreatogram, it was
      classified as either the stick type (n = 63), branch type (n = 15), saccular type
      (n = 15), spindle type (n = 11), or cudgel type (n = 8). In these groups, 49, 0,
      27, 82, and 87% of the APD were patent, respectively. The patency of the APD in
      the patients with acute pancreatitis was 6% (1 of 17). The difference in patency
      between this group and the control group was significant (p < 0.01). The patency
      of the APD varies with the shape of the terminal portion of the APD. A patent APD
      may prevent acute pancreatitis by lowering the pressure in the main pancreatic
      ducts.

PMID- 9018015
TI  - Fatal clinical course of ornithine transcarbamylase deficiency in an adult
      heterozygous female patient.
AB  - Ornithine transcarbamylase (OTC) deficiency is an X-linked inherited disease and
      the most common inborn error in urea synthesis in humans. In adult heterozygous
      patients, partial OTC deficiency can be responsible for life-threatening
      hyperammonemic coma, with a frequency of 15 %. We report the clinical course of a
      heterozygous female patient and discuss the therapeutic options, including
      hemodialysis and continuous arteriovenous hemofiltration for reduction of ammonia
      levels as well as liver transplantation as a definitive therapy.

PMID- 9018016
TI  - Beta-endorphin and cholecystokinin 8 concentrations in peripheral blood
      mononuclear cells of autistic children.
AB  - beta-Endorphin (beta-EP) and cholecystokinin 8 (CCK-8) concentrations in
      peripheral blood mononuclear cells were measured in 12 drug-free autistic (AU)
      children, in 10 drug-free children with pervasive developmental disorders (PDD)
      and in 11 healthy controls. The aim of the study was to see whether or not there
      was an alteration of beta-EP and CCK-8 concentrations in this peripheral
      compartment, in which it has been suggested that secretion and regulation of the
      two peptides mimic those of neurons in the central nervous system. Mean beta-EP
      values were significantly higher in AU than in PDD and control children, while
      there were no differences in CCK-8 values of the three groups.

PMID- 9018017
TI  - Acute dietary tryptophan depletion: effects on schizophrenic positive and
      negative symptoms.
AB  - Because brain serotonin levels depend directly on the amounts of exogenous
      tryptophan (TRP) available for its synthesis, amounts of TRP in the diet may be
      manipulated to alter the corresponding levels of serotonin. This technique has
      been used for probing the role of serotonin in mediating various forms of
      pyschopathology. In this study, 16 patients meeting DSM III-R criteria for
      schizophrenia (n = 14) or schizoaffective disorder (n = 2) were assessed for the
      effects of acute dietary TRP depletion under controlled conditions. The
      hypothesis was that lowering of serotonin would result in a diminution of
      'positive' and/or 'negative' symptoms of psychotic disorders. No clinically or
      statistically significant improvement compared to baseline occurred when TRP
      depletion was imposed. Indeed, there was a statistically significant
      deterioration on measures of negative symptoms. The results are discussed in the
      context of the methodological issues.

PMID- 9018018
TI  - GABA uptake sites in frontal cortex from suicide victims and in aging.
AB  - The binding of [3H]nipecotic acid to GABA uptake sites was studied in post mortem
      human frontal cortex from 17 suicide victims and 21 controls without known
      neurological or psychiatric disorder. The suicide victims were subclassified
      according to the use of violent or non-violent methods and to the presence or
      absence of a known history of a depressive disorder. No difference was found
      between the suicide victims and the controls with regard to [3H]nipecotic acid
      binding to GABA uptake sites (Bmax) and apparent affinity (Kd). No differences
      were found either with regard to method of suicide or whether a depressive
      symptom existed or not. The binding of [3H]nipecotic acid to GABA uptake sites
      was also studied in post mortem human frontal cortex with regard to aging. The
      age of the subjects ranged from 16 to 84 years. No significant difference in
      either Bmax or Kd was found. The present findings suggest that the GABA uptake
      sites in the human frontal cortex are not subjected to regulation or degenerative
      changes in conditions investigated.

PMID- 9018019
TI  - Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.
AB  - Carnitine is essential for mitochondrial energy production. Disturbance in
      mitochondrial function may contribute to or cause the fatigue seen in Chronic
      Fatigue Syndrome (CFS) patients. Previous investigations have reported decreased
      carnitine levels in CFS. Orally administered L-carnitine is an effective medicine
      in treating the fatigue seen in a number of chronic neurologic diseases.
      Amantadine is one of the most effective medicines for treating the fatigue seen
      in multiple sclerosis patients. Isolated reports suggest that it may also be
      effective in treating CFS patients. Formal investigations of the use of L
      carnitine and amantadine for treating CFS have not been previously reported. We
      treated 30 CFS patients in a crossover design comparing L-carnitine and
      amantadine. Each medicine was given for 2 months, with a 2-week washout period
      between medicines. L-Carnitine or amantadine was alternately assigned as fist
      medicine. Amantadine was poorly tolerated by the CFS patients. Only 15 were able
      to complete 8 weeks of treatment, the others had to stop taking the medicine due
      to side effects. In those individuals who completed 8 weeks of treatment, there
      was no statistically significant difference in any of the clinical parameters
      that were followed. However, with L-carnitine we found statistically significant
      clinical improvement in 12 of the 18 studied parameters after 8 weeks of
      treatment. None of the clinical parameters showed any deterioration. The greatest
      improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1
      patient was unable to complete 8 weeks of treatment due to diarrhea. L-Carnitine
      is a safe and very well tolerated medicine which improves the clinical status of
      CFS patients. In this study we also analyzed clinical and laboratory correlates
      of CFS symptomatology and improvement parameters.

PMID- 9018020
TI  - Placebo-controlled study of tianeptine in major depressive episodes.
AB  - The efficacy and safety of tianeptine were compared, in the course of a
      multicentre randomised, double-blind, parallel group study, to those of placebo
      in the treatment of Major Depressions and Bipolar Disorder, Depressed with or
      without melancholia, without psychotic features. After a 1-week run-in placebo
      period, 126 depressed out-patients presenting DSM-III-R Major Depression or
      Bipolar Disorder, Depressed, with a total MADRS score of at least 25, were
      treated for 42 days with either tianeptine (25-50 mg/day) or placebo. Efficacy
      assessments were MADRS, CGI, HARS, Zung Depression Self Rating Scale and a VAS.
      Better efficacy of tianeptine was shown, and confirmed by covariance analyses, in
      final MADRS scores of the intention-to-treat population, of patients treated for
      at least 14 days and of completers; also in CGI items 1 and 2, MADRS item 10, and
      VAS. The results confirmed the efficacy of tianeptine (mean dosage: 37.5 mg/day)
      in the treatment of Major Depression and Bipolar Disorder, Depressed, with or
      without melancholia, compared to placebo. Tianeptine's acceptability did not
      differ from that of placebo. For adverse events, a higher incidence of headaches
      was found with tianeptine.

PMID- 9018021
TI  - Active avoidance learning using brain stimulation applied to the inferior
      colliculus as negative reinforcement in rats: evidence for latent inhibition.
AB  - The inferior colliculus has been implicated in aversive or anxiogenic aspects of
      defensive behavior. Animals learn to turn off electrical stimulation applied to
      the inferior colliculus. The purpose of the present study was to determine (1)
      whether this aversion induced by electrical stimulation can be conditioned to a
      conditioned stimulus (CS, light) and (2) whether pre-exposure to the CS will
      diminish the extent of such conditioning, i.e. whether latent inhibition can be
      established with this paradigm. Rats were placed inside an open field, and
      thresholds for the escape response to electrical stimulation of the inferior
      colliculus were determined. The rats were then placed inside a shuttle box and
      submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior
      colliculus at the escape threshold was used as negative reinforcement and shuttle
      box illumination as the CS. The rats quickly learned to avoid or terminate the
      inferior-colliculus stimulation. Furthermore, the performance of the animals in
      this paradigm was significantly disrupted when they were pre-exposed to 50
      presentations of the CS before the session. These data suggest that the inferior
      colliculus has neural substrates for supporting associative learning and latent
      inhibition.

PMID- 9018022
TI  - Are there dissociable roles of the mesostriatal and mesolimbocortical dopamine
      systems on temporal information processing in humans?
AB  - There is some experimental evidence suggesting that temporal processing of brief
      duration in the range of milliseconds is based on dopamine (DA)-dependent neural
      counting mechanisms, whereas processing of longer duration is cognitively
      mediated. To further elucidate the critical role of DA receptors of the D2
      receptor family for temporal information processing in humans, the effects of the
      3 mg of haloperidol, 300 mg of sulpiride, and 150 mg of remoxipride were studied
      in a placebo-controlled double-blind experiment. In addition, concomitant changes
      in cortical arousal as well as speed of information processing and motor
      execution were measured. Temporal processing of brief duration was significantly
      impaired by haloperidol (p < 0.01) but not by sulpiride and remoxipride, whereas
      processing of longer duration was adversely affected by haloperidol (p < 0.001)
      as well as remoxipride (p < 0.01) as compared to placebo. The pattern of results
      in combination with the different pharmacological profiles of the dopaminergic
      drugs applied in the present study suggests that temporal processing of brief
      duration is mediated by D2 receptor activity in the mesostriatal system and,
      thus, point to the basal ganglia as a neuroanatomical structure possibly involved
      in timing of brief duration. On the other hand, deteriorating effects of D2
      receptor blockers on processing of longer duration appear to be due to DA-induced
      impairment of memory functions which may be mediated by the mesolimbocortical DA
      system.

PMID- 9018023
TI  - Chewing-gum flavor affects measures of global complexity of multichannel EEG.
AB  - Global complexity of spontaneous brain electric activity was studied before and
      after chewing gum without flavor and with 2 different flavors. One-minute, 19
      channel, eyes-closed electroencephalograms (EEG) were recorded from 20 healthy
      males before and after using 3 types of chewing gum: regular gum containing sugar
      and aromatic additives, gum containing 200 mg theanine (a constituent of Japanese
      green tea), and gum base (no sugar, no aromatic additives); each was chewed for 5
      min in randomized sequence. Brain electric activity was assessed through Global
      Omega (Omega)-Complexity and Global Dimensional Complexity (GDC), quantitative
      measures of complexity of the trajectory of EEG map series in state space; their
      differences from pre-chewing data were compared across gum-chewing conditions.
      Friedman Anova (p < 0.043) showed that effects on Omega-Complexity differed
      significantly between conditions and differences were maximal between gum base
      and theanine gum. No differences were found using GDC. Global Omega-Complexity
      appears to be a sensitive measure for subtle, central effects of chewing gum with
      and without flavor.

PMID- 9018024
TI  - Auditory vertex potential in children: a cognitive hypothesis.
AB  - In children the early N1P2 response generated by an auditory oddball paradigm is
      a compound negative potential with distinctive 165-ms temporal and 240-ms
      frontocentral components. As this configuration differs considerably from the
      adult response, it may be assumed that neural systems engaged in auditory
      attentional processes differ with age. It is argued that the auditory vertex
      potential might index frontal lobe development and matching mechanisms. In
      combination with EEG spectral data this cognitive parameter could initiate an
      alternative approach to the evaluation and research of learning and attention
      deficit disorders.

PMID- 9018025
TI  - Cervical artery dissections.
AB  - Cervical artery dissection (CAD) accounts for up to one fifth of ischemic strokes
      occurring before 45 years. Their increasing recognition is probably due to an
      increased clinical awareness of this condition in patients with painful ischemic
      events. The internal carotid artery is the most commonly affected vessel.
      Cerebral ischemia is the most serious consequence of a CAD. It may be due to
      hemodynamic factors or emboli. The enlargement of the artery may lead to a direct
      compression of the lower cranial nerves. CAD typically occurs in young adults
      with a mean age of 40 years with a male:female ratio of 1.5. After exclusion of
      traumatic cases, the average annual incidence rate of CAD is 2.6 per 100,000, but
      the reported incidence figures in the literature are likely to be an
      underestimation of the incidence of CAD. A spontaneous dissection is assumed when
      no or only minor trauma preceded the onset. However, the differentiation between
      spontaneous and traumatic dissections is artificial because of a continuum
      between both forms. The pathogenesis of dissections remains unknown in most
      cases. However, traumas and primary diseases of the arterial wall are the main
      predisposing factors. The clinical presentation of spontaneous dissections of the
      internal carotid artery includes cerebral ischemia, cervical or cranial pain,
      Horner's syndrome and cranial nerve palsy; CAD may also be silent. Brainstem
      ischemic deficits and occipital pain are the most common findings in vertebral
      artery dissections, but these features may be biased because the most benign and
      the most severe cases may escape detection. The favorable natural history of CAD
      emphasizes the need for a noninvasive approach to the detection, monitoring and
      follow-up. This noninvasive approach can be obtained by means of CT scan, MRI,
      magnetic resonance angiography and ultrasonography, although angiography remains
      the gold standard for the diagnosis of arterial dissections. Follow-up studies
      suggest a fairly good overall prognosis in adults and in children. In many
      centers, CAD are treated by heparin at the acute stage, although the benefit of
      such a potentially dangerous treatment has never been proven by a randomized
      trial.

PMID- 9018026
TI  - Alcoholic epilepsy: a unified and dynamic classification.
AB  - The interactions between alcohol and the CNS are complex and there are
      experimental data suggesting that chronic and acute effects are different and
      often opposite. An intriguing hypothesis is that repeated alcohol withdrawal
      seizures (AWS) may render the brain more excitable, leading to an epileptogenic
      state reminiscent of the 'kindling' model. To gain insight into this question we
      compared alcoholic patients with seizures related to episodes of AW (AWS) and
      patients with seizures unrelated to episodes of AW (UAWS). There were several
      significant differences between the AWS and UAWS groups. Age at admission for
      seizure was younger in the AWS groups (p < 0.005), seizure number was higher
      among patients with a history of seizures before admission in the UAWS group (p <
      0.05). Neurologic signs were more frequent in the UAWS group (p < 0.05). Duration
      of intoxication was longer in the UAWS group and brain atrophy demonstrated by CT
      scan was more common in the UAWS group than the AWS group. Based on these
      findings, we propose a dynamic classification in which patients presenting
      seizures unrelated to any cause other than alcohol are classified in several
      successive stages of 'alcoholic epilepsy', the first being characterized by AWS
      and the last by persistent chronic seizures.

PMID- 9018027
TI  - Cerebral oxygen metabolism in patients with progressive supranuclear palsy: a
      positron emission tomography study.
AB  - To investigate cerebral oxygen metabolism in progressive supranuclear palsy
      (PSP), 5 patients with a clinical diagnosis of PSP and a variable degree of
      cognitive deficit were selected for positron emission tomography (PET) of the
      brain. In 4 of them, a significant decrease in oxygen metabolism was found in all
      cortical regions, without frontal accentuation. In the group as a whole, this
      decrease was even slightly more marked in parietal and temporal regions. These
      findings are not consistent with earlier PET studies that demonstrated frontal
      targeting of hypometabolism in PSP patients. Part of this discrepancy can be
      explained by differences in methodology, although the use of different clinical
      criteria and overlap of PSP with other neurodegenerative diseases must be taken
      into account. It is concluded that the absence of frontal hypometabolism on PET
      examination does not exclude the diagnosis of PSP.

PMID- 9018028
TI  - Comparison of immediate-release and controlled release carbidopa/levodopa in
      Parkinson's disease. A multicenter 5-year study. The CR First Study Group.
AB  - BACKGROUND: Motor response fluctuations and dyskinesias compromise long-term
      levodopa therapy in Parkinson's disease. Variations in plasma levodopa levels
      contribute to adverse reactions associated with chronic therapy. Therefore,
      sustained-release levodopa preparations may be associated with less motor
      fluctuations and a better outcome. We conducted a large, 5-year, multicenter
      study to address this hypothesis. METHODS: Six hundred and eighteen
      nonfluctuating patients with Parkinson's disease never exposed to levodopa
      therapy were randomized to (Sinemet CR 50/200) sustained-release or immediate
      release (Sinemet 25/100) carbidopa/levodopa preparations in 35 centers worldwide.
      Dosage titration occurred over the 5 years of evaluations to maintain an optimal
      response. The primary endpoint, the 'event', was the presence of motor
      fluctuations, as defined by 20% 'off' time or 10% 'on' time with dyskinesias as
      recorded in the patient diary, or greater than or equal to a 50% positive
      response on the physician fluctuations questionnaire. Clinical rating scales,
      Nottingham Health Profile (NHP) and adverse reactions were also recorded.
      FINDINGS: During the 5 years of the study, both treatment groups responded
      extremely well to therapy. The incidence of all patients reaching the 'event' was
      low, approximately 20% by diary criteria and 16% by questionnaire definition, and
      there was no significant difference between the two treatment groups. Activities
      of daily living scores in the Unified Parkinson Disease Rating Scale (UPDRS)
      consistently favored the Sinemet CR treatment group and a number of the NHP
      scales also favored the CR group. Based upon the frequency of adverse
      experiences, and the overall low incidence of withdrawals, the two treatment
      groups demonstrated very similar safety profiles. The most common drug-related
      effect was nausea; seen in 20% of patients. Other drug-related effects were
      dizziness, insomnia, abdominal pain, dyskinesia, headache and depression. Drug
      related withdrawals were less than 10% of all patients, primarily due to
      nervous/psychiatric complaints. INTERPRETATION: During a 5-year treatment period,
      control of parkinsonian symptoms was maintained by both immediate-release and
      sustained-release carbidopa/levodopa. Both treatment regimens were associated
      with a low incidence of motor fluctuations and dyskinesias. There was a
      statistically significant difference (p < 0.05) in activities of daily living as
      measured by the UPDRS in favor of Sinemet CR.

PMID- 9018029
TI  - Aura phenomena during syncope.
AB  - We studied the frequency and clinical characteristics of aura phenomena in 60
      patients with cardiac and 40 subjects with vasovagal syncopes. The majority (93%)
      of all syncope patients recalled having experienced an aura. Aura phenomena were
      similar in both groups and were mostly compound auras comprising epigastric,
      vertiginous, visual, or somatosensory experiences, but were more detailed in the
      noncardiac group. The localizing significance of auras preceding a syncope was
      generally poor. Although hard to distinguish from epileptic auras from their
      structure and shape, syncope-related auras lacked symptoms that are commonly
      reported after epileptic seizures such as tastes, smells, deja vu phenomena,
      scenic visual perceptions, and speech impairments. A detailed anamnestic
      exploration of auras seems worthwhile in unexplained disorders of consciousness.

PMID- 9018030
TI  - Poor outcome of bilateral congenital choroid plexus papillomas with extreme
      hydrocephalus.
AB  - Bilateral choroid plexus papillomas, or villous hypertrophy of the choroid
      plexus, is a very rare entity that presents serious therapeutical problems in the
      management of secondary oversecretive hydrocephalus. The authors report the cases
      of 2 infants affected by this condition, and cured with removal of the lateral
      ventricle papillomas and with cerebrospinal fluid (CSF) ventriculoperitoneal
      shunt insertions. In both cases the CSF shunting alone or the removal of only 1
      papilloma did not suffice in controlling the intracranial hypertension. In both
      infants late outcome was unsatisfactory. The poor prognosis associated with
      bilateral choroid papillomas in the infants described in the present report may
      be explained by the precocious onset of the disease, diagnosed during fetal life,
      and by the marked cerebral alterations already apparent in the immediate
      postnatal period on the neuroradiological examinations. Repeated surgical
      procedures, which were necessary to control the associated hydrocephalus in these
      patients, might have also played a significant negative role.

PMID- 9018031
TI  - New mutations in the X-linked form of Charcot-Marie-Tooth disease.
AB  - Mutations in the gene for connexin 32 are associated with a chromosome X-linked
      form of Charcot-Marie-Tooth disease. The prevalence of this form is probably
      underestimated. We screened 12 candidate families and found 7 missense mutations
      of which 4 are new. These mutations are located in intra- and extramembraneous
      parts of the protein. Some mutations are probably present with a higher
      frequency. This study further confirms variation of connexin 32 mutations with
      scarcity in the second transmembrane domain and, so far, absence in the fourth
      transmembrane domain and in the carboxy-terminal region.

PMID- 9018032
TI  - Results of electroencephalographic monitoring during 369 consecutive carotid
      artery revascularizations.
AB  - A continuous intraoperative EEG monitoring was performed in 369 consecutive
      carotid artery revascularizations (CARs) (321 patients) to minimize the
      intraoperative neurological morbidity. There were 227 carotid endarterectomies
      and patch graft angioplasty (198 patients), 79 carotid eversion endarterectomies
      (70 patients) and 58 internal carotid artery reimplantations into the common
      carotid artery (48 patients). Indications for CARs were TIAs (141, 43.9%),
      amaurosis fugax (60, 18.6%) and fixed or partial nonprogressing stroke (14,
      4.3%). One hundred and six patients (33.1%) were asymptomatic. EEG abnormalities
      consistent with cerebral ischemia occurred in 97 (26.3%) operations. The
      indwelling shunt (IS) was used in 73 cases; in the remaining 24 (24.7%), IS was
      not used on purpose because the surgical procedure was carried out successfully
      within 5-6 min after the appearance of EEG changes. All patients awoke from the
      anesthesia without any neurological deficit. Five patients presented with a major
      stroke within postoperative day 1 and 2, and 1 patient died on postoperative day
      10. In 2 of these cases, the intraoperative EEG monitoring was absolutely normal
      and the IS was not used: the carotid occlusion was due to technical errors. The
      most striking finding of this series is the absence of false-negative results in
      continuous EEG monitoring. EEG monitoring appears an available and useful method
      for the detection of cerebral ischemia secondary to carotid cross-clamping and
      contributes to put at zero the intraoperative complications of the surgical
      procedure.

PMID- 9018033
TI  - Effects of HIV seropositivity and drug abuse on cognitive function.
AB  - Fifty-eight HIV-positive drug abusers and 22 HIV-positive nondrug abusers at
      stages II-III and IV of the Centers for Disease Control classification were
      evaluated neuropsychologically. The study confirmed previous findings that drug
      abuse has a negative influence on cognitive function. It also emerges that
      seropositivity affects cognitive function, although the poor performance of group
      II-III patients compared to group IV may be explained by factors related to
      seropositivity (anxiety and panic) rather than the disease itself. It is
      concluded that disease-related factors probably determine cognitive performance
      in the earlier stages of HIV infection.

PMID- 9018034
TI  - Autosomal dominant late-onset leukoencephalopathy. Clinical report of a new
      Italian family.
AB  - The adult-onset autosomal dominant leukoencephalopathies are rare disorders. Very
      few pedigrees have been extensively described and no biochemical or genetic
      marker has been identified so far. The present study was aimed to characterized
      an autosomal dominant late-onset leukoencephalopathy occurring in a large Italian
      kindred. A genealogic method was adopted to ascertain 51 affected individuals
      among nearly 400 subjects in 8 generations. Medical records were obtained from 11
      deceased patients. We personally examined 8 symptomatic and 9 asymptomatic at
      risk individuals who underwent a standardized clinical, biochemical, radiological
      and neurophysiological study. The mean age at onset of the disease was 46.6 years
      and the mean duration of disease 9.9 years. The clinical picture was
      characterized by progressive pyramidal and pseudobulbar signs, urinary
      incontinence and, sometimes, action tremor of the head and/or hands. No relevant
      mental deterioration was noted. In all the symptomatic and in 1 asymptomatic
      subject, brain MRI showed marked symmetrical hyperintensity on T2-weighted images
      of the white matter of the cerebral hemispheres, with constant sparing of the
      cerebellum. In these subjects, evoked potentials revealed altered central neural
      conduction. Nerve conduction velocity, biochemical (including lysosomal enzymatic
      activities) and biopsy (peripheral tissue specimens) examination were normal. The
      clinical and neuroradiological data are consistent with an autosomal dominant
      adult-onset leukoencephalopathy whose features are unusual when compared to those
      previously reported.

PMID- 9018035
TI  - Ipsilateral facial contracture due to pontine infarct.

PMID- 9018036
TI  - Hemispatial neglect in the visual hallucination of a patient with Anton's
      syndrome.

PMID- 9018037
TI  - A case of hemichorea-hemiballism associated with parietal lobe infarction.

PMID- 9018038
TI  - Treatment of dystonia occurring in parkinsonian syndromes by botulinum toxin.

PMID- 9018039
TI  - Pontine lesion of the abducens fasciculus producing so-called posterior
      internuclear ophthalmoplegia.

PMID- 9018040
TI  - The activation defect of a lambda cI positive control mutant.
AB  - "Positive control" mutants of the cI protein of bacteriophage lambda (lambda cI)
      bind DNA but, unlike the wild-type protein, fail to activate transcription.
      According to the original interpretation of Ptashne and co-workers, these mutants
      bear amino acid substitutions that disrupt a stimulatory interaction between
      lambda cI bound at operator site O(R)2 and RNA polymerase bound at promoter
      P(RM), an idea supported by kinetic analysis in one case. Genetic analysis has
      suggested that one residue in particular, glutamate 34 (E34), is critical for the
      stimulatory effect of wild-type lambda cI. More recently, however, Kolkhof and
      Muller-Hill have challenged this view, suggesting that mutant E34K fails to
      activate because it binds at unusually low concentrations to O(R)3, a site that
      mediates repression of P(RM). To test this hypothesis, we have examined the
      behaviour of the lambda cI-E34K mutant both in vitro and in vivo by assaying
      transcription from P(RM) and monitoring operator site occupancy over a range of
      protein concentrations. Our results are inconsistent with the interpretation of
      Kolkhof and Muller-Hill, and demonstrate that under conditions where lambda
      operator O(R)2 is fully occupied and operator O(R)3 is vacant, wild-type lambda
      cI activates transcription from promoter P(RM) whereas the mutant does not.

PMID- 9018041
TI  - A strong inhibitory element down-regulates SRE-stimulated transcription of the A3
      cytoplasmic actin gene of Bombyx mori.
AB  - To identify the functional regulatory elements of the promoter of the cytoplasmic
      actin A3 gene in Bombyx mori, transient expression of A3-LacZ mutants was assayed
      in cultured Lepidoptera cells. This led to the recognition of two proximal and
      contiguous domains exerting strong negative and positive effects, respectively on
      promoter activity. The negative region contains a ten-base-pair sequence that
      binds Bombyx silk gland cell nuclear proteins in vitro. The positive regulatory
      element was identified as a serum response element (SRE) by its sequence, and its
      in vitro binding properties. Moreover, structural analysis of posterior and
      median silk gland cell chromatin by dimethyl sulfate-aided LMPCR revealed that
      SRE is bound to its cognate factor in situ, in most, if not all, the
      approximately 100,000 A3 copies of the polyploid DNA stock. The regulation of the
      A3 promoter in the silk gland would thus result from the combined action of these
      two antagonist factors.

PMID- 9018042
TI  - A mutant T7 RNA polymerase that is defective in RNA binding and blocked in the
      early stages of transcription.
AB  - We have identified a mutation (E148A) in T7 RNA polymerase (RNAP) that results in
      an enzyme which aborts transcription primarily when the nascent RNA achieves a
      length of 5 nt. This phenomenon is observed at a consensus promoter, but is even
      more strongly observed at promoters that are altered in the initiation region.
      Although the abortive product is of a fixed length (5 nt), the positions of the
      base substitutions in the initiation region that enhance this effect do not
      appear to be fixed, and we have observed the effect with a variety of initiation
      region promoter variants. The phenomenon is also observed during promoter
      independent transcription when transcribing a homopolymeric template such as
      poly(dC). Under conditions where the active site of the RNAP cannot extend beyond
      the third nucleotide in the template strand and the maximum length of the RNA:DNA
      hybrid cannot exceed three base-pairs (i.e. when synthesizing oligoG products due
      to transcript slippage at a promoter that initiates with the sequence +1 GGG...)
      the mutant RNAP gives rise to a normal spectrum of products 2 to 14 nt in length
      with no evidence of a block at 5 nt. Neither promoter binding nor promoter
      melting appears to be involved in this phenotype, as the mutant RNAP binds
      normally to promoter sequences and the behavior of the enzyme is unaffected by
      removal of the non-template strand in the initiation region of the promoter or on
      a supercoiled template. Importantly, the mutant RNAP is defective in binding
      single strand oligomers of RNA. These results suggest that the affected region of
      the RNAP may form part of the RNA product binding site and may be involved in the
      transition from an unstable initiation complex to a stable elongation complex,
      perhaps by sensing the presence of a nascent RNA and/or RNA:DNA hybrid.

PMID- 9018043
TI  - Saccharomyces cerevisiae MSH2, a mispaired base recognition protein, also
      recognizes Holliday junctions in DNA.
AB  - Genetic and biochemical studies have suggested that mismatch repair proteins
      interact with recombination intermediates to prevent recombination, or to limit
      the extent of formation of heteroduplex DNA during recombination between
      divergent DNA sequences. To test the idea that mismatch repair proteins regulate
      recombination by interacting with recombination intermediates, we investigated
      whether the Saccharomyces cerevisiae MutS homolog MSH2 could interact with
      Holliday junctions. Both filter-binding and electron-microscopic analysis showed
      that MSH2 bound to duplex DNA molecules containing Holliday junctions with a
      higher affinity than to control duplex DNA, single-stranded DNA or a control
      duplex DNA containing a mispaired base. The MSH2-Holliday junction complexes were
      also more stable than MSH2-duplex DNA complexes. This observation suggests that
      MSH2 protein could directly coordinate the interaction between mismatch repair
      and genetic recombination observed in genetic studies.

PMID- 9018044
TI  - Leading versus lagging strand mutagenesis induced by 7,8-dihydro-8-oxo-2'
      deoxyguanosine in Escherichia coli.
AB  - We have previously shown that a single N-2-acetylaminofluorene (AAF) adduct bound
      to the C-8 position of a guanine residue located within plasmids containing the
      unidirectional ColE1 origin of replication induces a 20-fold higher mutation
      frequency when the adduct is located in the lagging strand as compared to the
      leading strand. In this study, single 7,8-dihydro-8-oxo-2'-deoxyguanosine (8
      oxodG) lesions have been introduced in the leading and lagging strand orientation
      within the same sequence context as for the AAF adducts. The induced frequency of
      guanine to thymine transversions has been measured, using a specific PCR-based
      quantitative assay, in strains deficient in the repair of the oxidative lesion.
      The potential involvement of the UvrABC excision repair system in the removal of
      8-oxodG has also been investigated and ruled out. Concerning the mutation
      frequency asymmetry, in contrast to AAF adducts, 8-oxodG adducts induce the same
      mutation frequency, irrespective of their location in the leading or lagging
      strands. This striking difference between 8-oxodG and dGuo-C8-AAF adducts is
      discussed in terms of their differential capacity to block DNA replication.

PMID- 9018045
TI  - Vibrio alginolyticus mutants resistant to phenamil, a specific inhibitor of the
      sodium-driven flagellar motor.
AB  - The polar flagella of Vibrio alginolyticus are driven by sodium motive force and
      those motors are specifically and strongly inhibited by phenamil, an amiloride
      analog that is thought to interact with a sodium channel of the flagellar motor.
      To study the sodium ion coupling site, we isolated motility mutants resistant to
      phenamil and named the phenotype Mpa(r) for motility resistant to phenamil. The
      motility of the wild-type (Mpa(s)) was inhibited by 50 microM phenamil, whereas
      Mpa(r) strains were still motile in the presence of 200 microM phenamil. The Ki
      value for phenamil in the Mpa(r) strain was estimated to be five times larger
      than that in the Mpa(s) strain. However, the sensitivities to amiloride or
      benzamil, another amiloride analog, were not distinctly changed in the Mpa(r)
      strain. The rotation rate of the wild-type Na+-driven motor fluctuates greatly in
      the presence of phenamil, which can be explained in terms of a relatively slow
      dissociation rate of phenamil from the motor. We therefore studied the stability
      of the rotation of the Mpa(r) and Mpa(s) motors by phenamil. The speed
      fluctuations of the Mpa(r) motors were distinctly reduced relative to the Mpas
      motors. The steadier rotation of the Mpa(r) motors can be explained by an
      increase in the phenamil dissociation rate from a sodium channel of the motor,
      which suggests that a phenamil-specific binding site of the motor is mutated in
      the Mpa(r) strain.

PMID- 9018046
TI  - Proximal regions of the catalytic gamma and regulatory beta subunits on the
      interior lobe face of phosphorylase kinase are structurally coupled to each other
      and with enzyme activation.
AB  - Phosphorylase kinase from skeletal muscle is a hexadecameric enzyme with the
      subunit composition (alphabeta gammadelta)4 and a mass of 1.3 x 10(6) Da. The
      catalytic gamma subunit and the remaining regulatory subunits are packed as a
      tetrahedral structure composed of two elongated, opposing (alphabeta gammadelta)2
      octameric lobes. We show by immunoelectron microscopy with subunit-specific
      monoclonal antibodies that a portion of the beta subunit occurs on the interior
      face of the lobes at a region of inter-lobal interactions, and that at a proximal
      position slightly more central and distal on the interior lobe face lies the base
      (residues 277 to 290) of the helical domain of the catalytic core of the gamma
      subunit. Activation of the kinase by a variety of means caused similar increases
      in the binding to the holoenzyme of the monoclonal antibodies against these two
      regions of the beta and gamma subunits. Moreover, monovalent fragments of the
      antibodies against both regions stimulated the activity of the non-activated
      holoenzyme. Thus, the epitopes of the beta and gamma subunits recognized by the
      monoclonal antibodies are structurally coupled to each other and with the
      activation of phosphorylase kinase. Activation of the holoenzyme apparently
      involves the repositioning of the base of the catalytic domain of the gamma
      subunit and a proximal region of the beta subunit within the identified area on
      the interior face of the lobes of the tetrahedral phosphorylase kinase molecule.

PMID- 9018047
TI  - Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent
      formaldehyde dehydrogenase.
AB  - The crystal structure of the human class III chi chi alcohol dehydrogenase (ADH)
      in a binary complex with NAD+(gamma) was solved to 2.7 A resolution by molecular
      replacement with human class I beta1 beta1 ADH. chi chi ADH catalyzes the
      oxidation of long-chain alcohols such as omega-hydroxy fatty acids as well as S
      hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and
      glutathione. There are two subunits per asymmetric unit in the chi chi ADH
      structure. Both subunits display a semi-open conformation of the catalytic
      domain. This conformation is half-way between the open and closed conformations
      described for the horse EE ADH enzyme. The semi-open conformation and key changes
      in elements of secondary structure provide a structural basis for the ability of
      chi chi ADH to bind S-hydroxymethyl-glutathione and 10-hydroxydecanoate. Direct
      coordination of the catalytic zinc ion by Glu68 creates a novel environment for
      the catalytic zinc ion in chi chi ADH. This new configuration of the catalytic
      zinc is similar to an intermediate for horse EE ADH proposed through theoretical
      computations and is consistent with the spectroscopic data of the Co(II)
      substituted chi chi enzyme. The position for residue His47 in the chi chi ADH
      structure suggests His47 may function both as a catalytic base for proton
      transfer and in the binding of the adenosine phosphate of NAD(H). Modeling of
      substrate binding to this enzyme structure is consistent with prior mutagenesis
      data which showed that both Asp57 and Arg115 contribute to glutathione binding
      and that Arg115 contributes to the binding of omega-hydroxy fatty acids and
      identifies additional residues which may contribute to substrate binding.

PMID- 9018048
TI  - Inhibitory mechanism of serpins. Identification of steps involving the active
      site serine residue of the protease.
AB  - The role of the protease active-site serine residue in the formation of protease
      serpin complexes has been investigated by using a mutant of thrombin in which
      Ser195 was mutated to alanine (S195A). The structural integrity of S195A was
      established by examining the kinetics of its interaction with the inhibitor
      hirudin, which does not have substantial interactions with Ser195. The affinity
      of S195A for hirudin was only tenfold less than that of thrombin and the kinetic
      constants for the formation of the S195A-hirudin complex were very similar to
      those observed with thrombin. In contrast to hirudin, the dissociation constants
      (Ki) for S195A with serpins (antithrombin, protease nexin-1 and alpha1
      antitrypsin with a P1 arginine) were 2 x 10(3) to 2 x 10(5)-fold higher than
      those observed with thrombin. These results indicate a critical role for
      interactions with Ser195 in stabilizing the thrombin-serpin complexes. The
      cofactor heparin compensated partially for the loss of interactions with Ser195;
      it increased the affinity of S195A for protease nexin-1 and antithrombin by 140
      fold and 1000-fold, respectively. In the case of heparin/antithrombin, the
      increase in affinity could be attributed mainly to interactions outside the
      active site of S195A. Kinetic studies with antithrombin and protease nexin-1 in
      the presence of heparin indicated that Ser195 was not involved in any rate
      limiting process in the formation of protease-serpin complexes. Interactions with
      Ser195 increased the stability of the complex by markedly reducing its rate of
      breakdown rather than by increasing its rate of formation. Overall, the results
      of the kinetic studies were consistent with a mechanism in which the binding of
      the protease induces a rate-limiting conformational change in the serpin and
      interactions with the protease's active-site serine residue, occurring in a
      subsequent faster step, greatly stabilize the complex.

PMID- 9018049
TI  - The molecular biology of caliciviruses.

PMID- 9018050
TI  - Mapping of antigenic sites involved in neutralization on the capsid protein of
      feline calicivirus.
AB  - In order to locate amino acid residues involved in the formation of feline
      calicivirus (FCV) neutralizing epitopes, we analysed the capsid protein gene of
      monoclonal antibody neutralization-resistant variants of FCV. Amino acid
      substitutions in the variants were identified in the two hypervariable regions of
      the capsid protein. Four linear and two conformational epitopes were located in
      the regions from residues 426 to 460 and 490 to 520, respectively. The relative
      positions of individual epitopes agreed with our previous antigenic analysis. Two
      antigenic sites composed of the neutralizing epitopes were mapped in the
      hypervariable regions of the capsid protein, demonstrating that a relationship
      exists between the genetic variability and antigenic differences in the
      neutralization of FCV.

PMID- 9018051
TI  - Evidence for enteroviral persistence in humans.
AB  - We have sought evidence of enteroviral persistence in humans. Eight individuals
      with chronic fatigue syndrome (CFS) were positive for enteroviral sequences,
      detected by PCR in two serum samples taken at least 5 months apart. The
      nucleotide sequence of the 5' non-translated region (bases 174-423) was
      determined for each amplicon. Four individuals had virtually identical nucleotide
      sequences ( > 97%) in both samples. The sequence pairs also each had a unique
      shared pattern indicating that the virus had persisted. In one individual (HO),
      it was clear that there had been infection with two different enteroviruses. In
      the remaining three individuals, the lack of unique shared features suggested
      that re-infection had occurred, rather than persistence. With the exception of
      HO, the sequences fell into a subgroup that is related to the Coxsackie B-like
      viruses.

PMID- 9018052
TI  - Taura syndrome of marine penaeid shrimp: characterization of the viral agent.
AB  - The causative agent of Taura syndrome (TS) was recognized in 1994 to be viral in
      nature and tentatively classified as belonging to either the family
      Picornaviridae or Nodaviridae. The work reported here has led to a more
      definitive classification of this new penaeid virus. Located within the cytoplasm
      of infected cuticular epithelial cells of penaeid shrimp, the virus is a 31 to 32
      nm icosahedral particle with a buoyant density of 1.338+/-0.001 g/ml. Three major
      (55, 40 and 24 kDa) and one minor (58 kDa) polypeptides constitute its proteinic
      capsid. Its genome contains a single molecule of ssRNA, which is polyadenylated
      at the 3' end and approximately 9 kb in length. Based on these characteristics,
      we believe that TS virus should be included in the family Picornaviridae.
      Ecuadorian and Hawaiian TS virus isolates were found to be identical in their
      biophysical, biochemical and biological characteristics, and should be considered
      as the same virus.

PMID- 9018053
TI  - The origin of hepatitis C virus genotypes.
AB  - For many RNA viruses, relatively recent times of origin of extant viruses are
      implied by the high rate of substitution observed in longitudinal studies.
      However, extrapolation of short-term rates of substitution can give misleading
      estimates of times of divergence. We show here that the common ancestor of
      different types of hepatitis C virus (HCV) is older than previously thought. The
      rate of HCV sequence change was measured amongst a cohort of individuals infected
      following administration of anti-D immunoglobulin. Virus sequences were obtained
      in the E1 and NS5B genes and compared with each other and with sequences from an
      infective batch. Taking account of the bias towards synonymous transition
      substitutions, the time of divergence of variants of subtype 1b is estimated to
      have occurred 70-80 years ago. The numerous subtypes of HCV are proposed to
      derive from more than 300 years of endemic infection in certain geographical
      regions, with recent spread of some subtypes to other parts of the world.
      Estimation of the time of origin of the major HCV genotypes (types 1-6) is
      problematic, but our data and analogy with other viruses suggest that divergence
      occurred at least 500-2000 years ago.

PMID- 9018054
TI  - Genetic analysis of the hepatitis C virus (HCV) genome from HCV-infected human T
      cells.
AB  - We recently established a cell culture system for the replication of hepatitis C
      virus (HCV) by using a human T cell leukaemia virus type I-infected cell line, MT
      2, and showed that the quasi-species of the hypervariable region 1 observed in
      the original inoculum became homogeneous in MT-2 cells 10 days after inoculation
      of HCV. In this study, we obtained HCV cDNA clones covering the whole viral
      genome by RT-nested PCR using RNA from HCV-infected cloned MT-2C cells, which
      support viral replication more efficiently, at 12 days after inoculation. A total
      of 41 distinct HCV cDNA clones covering almost the whole viral genome were also
      isolated from a cDNA library derived from the original inoculum. Molecular
      evolutional analyses comparing the sequences of the HCV clones obtained from both
      sources revealed that the HCV populations became homogeneous in more than half of
      the compared regions. This finding suggests that limited HCV populations are able
      to replicate in MT-2C cells. In addition, we isolated cDNA clones containing a 3'
      X-tail sequence, which was recently identified as a bona fide 3' terminus of the
      HCV genome, in the HCV-infected MT-2C cells and confirmed that the nucleotide
      sequence of the 3' X-tail was highly conserved, suggesting its implication in HCV
      replication. Finally, on the basis of the sequences of HCV cDNA clones obtained
      from HCV-infected MT-2C cells, we determined the entire nucleotide sequence of
      the HCV genome containing the 3' X-tail as a candidate for an infectious HCV
      molecular clone.

PMID- 9018055
TI  - Internal proteolysis of the NS3 protein specified by dengue virus 2.
AB  - The NS3 protein of flaviviruses is a multifunctional polypeptide required for
      virus replication. Enzymic activities that have been demonstrated or predicted
      from the presence of sequence motifs include protease, NTPase, helicase and RNA
      triphosphatase. Both full-length and truncated forms of NS3 have been identified
      in infected cells. To examine internal cleavage of the NS3 protein of dengue
      virus 2 (DEN-2), infected cells or COS cells transfected with cDNA encoding
      NS2B/3 were radiolabelled and immunoprecipitated with antiserum against NS3 or
      hyperimmune mouse ascitic fluid. The polypeptides detected were NS2B/3 (Mr
      83000), NS3 (Mr 69000), NS3' (Mr 50000) and NS3" (Mr 19000). The latter
      polypeptide has not been previously identified. For DEN-2, it has been proposed
      that NS3' results from cleavage at the site ...R457R / GR460... within an RNA
      helicase sequence motif of NS3. Our results demonstrated that cleavage occurred
      at this site, and that prior cleavage between NS2B/NS3 was not necessary.

PMID- 9018056
TI  - Monoclonal antibodies specific for Semliki Forest virus replicase protein nsP2.
AB  - A panel of monoclonal antibodies (MAbs) was raised against Semliki Forest virus
      (SFV) nonstructural protein nsP2, which is a protease, an NTPase, a putative RNA
      helicase, and a regulator of the synthesis of the subgenomic 26S mRNA encoding
      the structural proteins. nsP2, used for immunization, was expressed as a
      histidine fusion protein in Escherichia coli and purified by metal affinity
      chromatography. Dot-blot assay, using a membrane fraction from SFV-infected cells
      as antigen, gave 33 positive clones. Of these, 30 MAbs recognized nsP2 in Western
      immunoblotting, and 25 showed positive indirect immunofluorescence (IFAT) in SFV
      infected cells; 15 MAbs stained the cytoplasmic vacuoles (CPVI), which are the
      sites of viral RNA synthesis in alphavirus-infected cells. MAb 3B5 recognized
      only CPVIs, as shown by double immunofluorescence staining with polyclonal anti
      nsP3 antiserum. Most of the MAbs (20/33) recognized the nuclear form of nsP2,
      which may be associated with SFV neurovirulence. Immunoprecipitation with MAbs
      revealed that the SFV nonstructural proteins are associated with each other. None
      of the MAbs recognized Sindbis virus nsP2 in immunoblotting, indicating that they
      were directed to non-conserved sequences specific for SFV. Interestingly, these
      epitopes were located mostly within the N-terminal half of nsP2. Unexpectedly,
      the anti-nsP2 MAb 1E9 cross-reacted strongly with a host protein of 78 kDa from
      uninfected human, murine, avian and insect cells. This protein was identified as
      the immunoglobulin binding protein, BiP, by 2-D gel mapping and reaction with
      anti-BiP antiserum.

PMID- 9018057
TI  - Mutational analysis of the RNA-fork model of the influenza A virus vRNA promoter
      in vivo.
AB  - The genome of influenza A virus consists of eight negative-stranded RNA segments
      which have partially complementary non-coding terminal sequences. Previous
      transcription studies of the virion RNA promoter in vitro have shown that the 5'
      terminus forms an integral part of the promoter and an 'RNA-fork' model has been
      proposed for the initiation of transcription. According to this model part of the
      promoter is formed by an RNA-duplex which involves complementary residues 10 to 1
      2 of the 3' end and residues 11' to 13' of the 5' end. With a reverse genetics
      system, based on the chloramphenicol acetyltransferase (CAT) gene, we have now
      tested this part of the promoter in vivo. Single mutations of the conserved
      residues at positions 11 and 12 of the 3' terminus and at positions 12' and 13'
      of the 5' terminus abolished promoter activity. The introduction of complementary
      mutations into both termini partially restored activity. On the other hand,
      mutations at positions 10 of the 3' terminus and 11' of the 5' terminus inhibited
      activity independently of whether a base-pair was formed or not. Thus, at these
      positions, the nature of the residues is apparently more important than their
      ability to form base-pairs. These results extend our previous virion 'RNA-fork'
      model and are consistent with in vitro findings that the 5' terminus is involved
      in the initiation of transcription.

PMID- 9018058
TI  - Antigenic and molecular analyses of the variability of bovine respiratory
      syncytial virus G glycoprotein.
AB  - Antigenic variation among eight bovine respiratory syncytial virus (BRSV)
      isolates was determined using monoclonal antibodies (MAbs) specific for the
      attachment (G) protein. Two major (and one intermediate) subgroups were
      identified, as well as one strain that did not fit any pattern. The subgroups
      could also be differentiated on the basis of the Mr of the F protein cleavage
      product, F2. The nucleotide sequence of the G gene of seven of the BRSV strains
      was determined and compared with published G gene sequences. Subgroups A and A/B
      were more closely related in protein sequence than subgroups A and B or subgroups
      A/B and B. These results could not be correlated with those obtained by the
      determination of the Mr of the F2 polypeptide. Multiple sequence alignments
      showed a high level of amino acid identity at the inter-subgroup level (85%
      identity between subgroup A and subgroup B strains), similar to the intra
      subgroup human (H)RSV identity, suggesting that the BRSV isolates form a
      continuum rather than distinct subgroups. However, unusual variability was
      observed within the immunodominant domain (amino acids 174-188) in contrast with
      the situation in HRSV strains belonging to the same subgroup.

PMID- 9018059
TI  - Genetic diversity of the attachment (H) protein gene of current field isolates of
      canine distemper virus.
AB  - To characterize the variability of recent field isolates of canine distemper
      virus (CDV) from different hosts and geographical areas, we conducted nucleotide
      sequence analysis of the gene encoding the haemagglutinin (H), the attachment
      protein of this virus. Pronounced differences between field isolates were
      revealed in comparison to the Convac and Onderstepoort vaccine strains. The
      diversity of CDV appeared to exceed that determined for measles virus.
      Phylogenetic analysis also separated the field isolates of CDV from the vaccine
      strains and provided evidence for the existence of different contemporary
      genotypes of CDV. Isolates from a Greenlandic sledge dog and a Siberian seal
      formed a distinct lineage. The remaining isolates formed a group. This group
      contained two European isolates from mink and ferret, a single lineage comprising
      three European dog isolates, and another separate lineage of North American
      isolates from dog, javelina, raccoon and captive leopards.

PMID- 9018060
TI  - Molecular and phylogenetic analyses of the haemagglutinin (H) proteins of field
      isolates of canine distemper virus from naturally infected dogs.
AB  - We isolated three strains of canine distemper virus (CDV)--the Ueno, Hamamatsu,
      and Yanaka strains--from dogs in Japan and analysed the molecular properties of
      their haemagglutinin (H) proteins. Immunoprecipitation of all three strains with
      a monoclonal antibody revealed H proteins with molecular masses of 84 kDa, which
      differs from the molecular mass (78 kDa) of the H protein of the Onderstepoort
      vaccine strain. However, after tunicamycin treatment immunoprecipitation
      identified H proteins of identical molecular mass (68 kDa) for all three field
      isolates and the vaccine strain. Sequence analysis showed nine potential sites
      for asparagine-linked glycosylation in the H proteins of the new isolates, in
      contrast to four in the H protein of the Onderstepoort strain. Thus, variation in
      glycosylation of the H proteins of the isolates and the vaccine strain may cause
      differences in antigenicity of the viruses. Sequences of the H genes showed that
      the new Japanese isolates have 99% identity with each other, 95% with other
      European and American isolates (from seals, a German dog, a ferret and large
      felids) and 90% with the vaccine strain. Phylogenetically, the new Japanese
      isolates form one cluster which is separate from recent European or American
      isolates, all of which are distinct from vaccine strains.

PMID- 9018061
TI  - Regulated expression vectors demonstrate cell-type-specific sensitivity to human
      immunodeficiency virus type 1 Nef-induced cytostasis.
AB  - The nef gene product of both human and simian immunodeficiency viruses is
      critically important for virus replication and disease progression in vivo.
      However, the precise biological function of Nef remains poorly characterized in
      vitro, with previous reports suggesting that Nef might be either cytotoxic or
      cytostatic. As a result of difficulties encountered by several groups in
      establishing cell lines constitutively expressing Nef, we have developed two
      inducible systems resulting in stable Nef expression in various mammalian cell
      lines. Tetracycline-regulated Nef expression was achieved in HeLa cells but could
      not be established in human T cell lines. Jurkat E6-1 T cell and RAW264.7 murine
      macrophage cell lines expressing a regulated nef gene were generated using a
      system in which Nef expression was controlled by a mutated version of the heavy
      metal-inducible human metallothionein IIA promoter. Induction of high levels of
      Nef expression in HeLa-Nef and Jurkat-Nef cells resulted in a moderate (2-fold)
      and a dramatic (10-fold) retardation of cell growth respectively, supporting the
      contention that Nef may be a cytotoxic or cytostatic factor. This property was
      also observed at low basal levels of Nef expression in RAW264.7-Nef macrophage
      clones (5-fold reduction in growth) and was associated with an altered
      morphological phenotype suggesting that different cell types may be more
      susceptible to the cytostatic activity of Nef. The regulated Nef-expression
      systems provide tools for investigating the molecular basis of Nef function,
      including Nef-mediated cytopathogenicity, CD4 down-regulation and enhancement of
      virus infectivity.

PMID- 9018062
TI  - Diversity of the vif gene of human immunodeficiency virus type 1 in Uganda.
AB  - Little sequence information is available for human immunodeficiency virus type 1
      (HIV-1) vif genes of African origin. Here we describe 37 new complete vif genes
      of 18 AIDS patients from Uganda and show that vif has a high in vivo genetic
      variability. vif proviral DNA sequences of peripheral blood cells were determined
      by direct sequencing of PCR products. Only 52% of the deduced Vif amino acids
      were absolutely conserved; when Vif sequences previously analysed were
      considered, only 32% of the Vif consensus sequence comprised conserved and as
      such possibly functionally important motifs. The high inter-individual vif
      variability was in contrast to a very low intra-individual variability. One
      patient carried a vif gene with a stable C-terminal deletion, but N-terminal
      truncations were not found in patients' predominant vif sequences. The vif genes
      analysed comprised subtypes A, D and an A/D mosaic. Phylogenetic analyses
      additionally showed that HIV- 1 in Uganda has spread across the boundaries of
      ethnic groups.

PMID- 9018063
TI  - Expression of AP1 during cellular differentiation determines human papillomavirus
      E6/E7 expression in stratified epithelial cells.
AB  - E6 and E7 oncoproteins of human papillomavirus (HPV) play significant roles in
      the pathogenesis of cervical cancer. However, the pattern of E6/E7 expression
      during the productive virus life cycle in differentiating epithelia of the
      uterine cervix remains unclear. In addition, little is known about the cellular
      factors regulating E6/E7 expression in differentiating epithelia. In the present
      study, using transient expression assays and DNA binding assays, we demonstrated
      that E6/E7 transcription is critically regulated by the cellular factor AP1, a
      Jun/Fos heterodimer complex. Immunohistochemical analyses of various uterine
      cervical lesions showed AP1 expression in lower cell layers of normal cervix and
      low-grade cervical intraepithelial neoplasia (CIN), while it was detected
      throughout all layers in high-grade CIN and invasive cancer. In situ RNA-RNA
      hybridization analyses of organotypic raft culture specimens of an HPV-31
      containing cell line revealed that E6/E7 transcripts were expressed in most cell
      layers, with reduced expression in differentiated cells. This pattern of HPV
      expression correlated with the pattern of AP1 expression detected by
      immunohistochemical analyses. These findings suggest that E6/E7 expression in
      differentiating epithelia is dependent on AP1, which appears to be associated
      with proliferative activity of the cells. Since E6/E7 expression induces cell
      proliferation, co-expression of AP1 and E6/E7 in undifferentiated cell layers
      might create a positive regulatory loop, probably contributing to maintenance of
      initial HPV infection and subsequent activation in basal and suprabasal cell
      layers.

PMID- 9018064
TI  - The E1A N terminus (aa 1-29) of the highly oncogenic adenovirus type 12 harbours
      a trans-activation function not detectable in the non-oncogenic serotype 2.
AB  - Early region 1A (E1A) of adenoviruses (Ad) codes for potent activator and
      repressor molecules which are involved in the regulation of viral and cellular
      gene expression. Gene regulatory functions of E1A proteins are mainly located in
      their conserved regions (CR) 1 to 3. In addition to the CRs, specific amino acids
      (aa) of the N-terminal end play an important role in some gene regulatory
      functions. We describe here the identification and characterization of a novel
      trans-activation domain which is located in the non-conserved N-terminal end of
      Ad12 E1A, namely aa 1-29. Fusion of this region to the DNA-binding domain of the
      yeast transcription factor Gal4 generates a strong trans-activator which induces
      gene expression of reporter constructs in dependence on Gal4 DNA-binding sites.
      Furthermore, transient expression assays using the physiological E1A-responsive
      adenoviral E2 early promoter revealed that the N terminus is involved in its
      activation. The gene regulatory function of the N terminus is specific for E1A
      proteins of the highly oncogenic serotype Ad12, as the respective E1A N terminus
      of the non-oncogenic serotype Ad2 is unable to activate the expression of the
      reporter gene as Gal4 fusion protein. Moreover, deletion mutant analyses
      demonstrate that Ad12 E1A proteins carry three independently acting activation
      domains: (1) aa 1-29, (2) CR1 and (3) CR3.

PMID- 9018065
TI  - The adenovirus 12 E1A proteins can bind directly to proteins of the p300
      transcription co-activator family, including the CREB-binding protein CBP and
      p300.
AB  - The cellular transcription co-activators p300 and the CREB-binding protein CBP
      are cellular targets for transformation by the E1A proteins of non-oncogenic
      adenovirus 5 (Ad5). In this study, we show that the E1A proteins of oncogenic
      Ad12, like those of Ad5, can also bind to CBP and that this interaction is
      direct. In addition, we show that the Ad12 E1A proteins can also bind directly to
      p300. These results suggest that E1A can modulate the function of proteins of the
      p300 family via direct protein-protein interactions.

PMID- 9018066
TI  - Protective immunity against herpes simplex virus (HSV) type 1 following oral
      administration of recombinant Salmonella typhimurium vaccine strains expressing
      HSV antigens.
AB  - Salmonella typhimurium strains expressing foreign antigens of various pathogens
      are capable of eliciting antigen-specific humoral and cellular immune responses.
      Attenuated S. typhimurium strain chi4550 (delta(cya) delta(crp) delta(asd)) was
      used as an expression vector for herpes simplex virus (HSV) antigens. Genes
      encoding glycoprotein D (gD) and the immediate-early protein ICP27 of HSV-1 were
      cloned and expressed in plasmid pYA292 (asd+) and subsequently placed into
      chi4550. Following two oral immunizations, the protective efficacy of recombinant
      strains against zosteriform challenge with HSV-1 was measured in 3-4-week-old
      BALB/c mice. Levels of protection observed were 77% with the ICP27 construct but
      only 31% with the gD construct. Zosteriform protection correlates with a CD4+
      mediated delayed-type hypersensitivity (DTH) reaction against HSV. Accordingly,
      significant DTH was observed only in mice immunized orally with the S.
      typhimurium ICP27 construct. ELISA analysis of antigen-specific humoral responses
      failed to detect serum antibody responses following oral administration although
      recombinant S. typhimurium were isolated from spleens of orally dosed mice up to
      day 30. Intravenous (i.v.) immunization with the gD-expressing construct did,
      however, induce detectable serum antibody responses. Some humoral IgA responses
      against gD in faecal samples were detected as early as 3 weeks post-oral
      immunization while those induced by the i.v. route were slightly lower. These
      data suggest that recombinant S. typhimurium HSV antigens are capable of inducing
      immunity against HSV, some aspects of which are protective against HSV challenge.

PMID- 9018067
TI  - Persistence of ribosomal protein synthesis after infection of HeLa cells by
      herpes simplex virus type 1.
AB  - Because synthesis of rRNA persists late during herpes simplex type 1 infection
      and because S6 phosphorylation is always correlated with efficient translation of
      ribosomal protein mRNA, we tested the hypothesis that ribosomal protein synthesis
      and ribosome biogenesis could persist after infection. At different times after
      infection, proteins were labelled with 35S for 1 h before harvesting and
      ribosomes were purified. Measurement of radioactivity incorporated into
      individual ribosomal proteins separated by two-dimensional PAGE demonstrated that
      ribosomal proteins are still synthesized and assembled into mature ribosomes up
      to late times during infection, while synthesis of beta-actin is severely
      inhibited. During expression of late genes, ribosome biogenesis was estimated to
      be 58% of that of the control as judged by [3H]uridine incorporation into rRNA.
      As for beta-actin mRNA, the level of ribosomal protein mRNA decreased
      progressively from the beginning of infection, reaching about 30% of the control
      level during expression of late genes. Taken together, these results demonstrate
      that ribosomal proteins are still synthesized up to the late time of infection
      and efficiently assembled into mature ribosomes, while there is a severe shutoff
      of the synthesis of other cellular proteins.

PMID- 9018069
TI  - Amino acid changes in the putative replicase of tomato mosaic tobamovirus that
      overcome resistance in Tm-1 tomato.
AB  - Replacement of Gln-979 by Glu in the putative replicase of tomato mosaic
      tobamovirus is sufficient to overcome Tm-1 resistance in tomato. It has been
      suggested that this change decreases the local net charge of the protein which is
      important in overcoming the resistance. In this study, we constructed five
      mutants, designated TLAsn, TLAsp, TLHis, TLLys and TLArg, in which Gln-979 was
      replaced by Asn, Asp, His, Lys and Arg, respectively, and analysed their
      abilities to overcome Tm-1 resistance. Unexpectedly, not only TLAsp, but also
      TLLys multiplied in tomato cells with the Tm-1 gene. TLAsn and TLArg multiplied
      at a reduced level. Multiplication of TLHis was virtually almost inhibited. From
      these results, it is unlikely that a decrease in the local net charge is the
      major reason for overcoming Tm-1 resistance.

PMID- 9018068
TI  - Cell type-specific expression in brain cell cultures from a short human
      cytomegalovirus major immediate early promoter depends on whether it is inserted
      into herpesvirus or adenovirus vectors.
AB  - Expression from a short human cytomegalovirus (HCMV) major immediate early (IE)
      promoter-enhancer was tested in three different virus vectors: recombinant
      adenovirus (Ad), recombinant herpes simplex virus type 1 (HSV-1) and HSV-1
      derived amplicon vectors. The HCMV major IE promoter-enhancer within a
      replication-deficient recombinant Ad vector was shown to produce cell-specific
      expression in rat nervous system cell cultures. Recombinant Ad entered all cell
      types examined but the HCMV major IE promoter was silent in primary cultures of
      neocortical neurons and Schwann cells, although it drove transgene expression in
      astrocytes and fibroblasts. Moreover, in neurons and Schwann cells, expression
      from the HCMV major IE promoter-enhancer in the replication-deficient Ad vector
      was activated by superinfection with HSV-1, replication-competent Ad and HCMV.
      The HCMV major IE promoter-enhancer was active in neurons when inserted into HSV
      1 recombinant vectors. Further experiments with HSV-1-derived amplicons strongly
      suggested that an IE protein was responsible for the activation of HCMV major IE
      induced expression in neurons. This demonstrates that the activity of the HCMV
      major IE promoter-enhancer element can depend on the expression of other genes
      encoded in the virus vector backbone within which it is inserted, and that it can
      function in a neuronal cell type-specific manner when inserted into a replication
      deficient Ad vector.

PMID- 9018070
TI  - Transmission of tobacco rattle virus isolate PpK20 by its nematode vector
      requires one of the two non-structural genes in the viral RNA 2.
AB  - Tobacco rattle virus isolate PpK20 is transmitted by the nematode Paratrichodorus
      pachydermus. RNA 2 of the virus determines vector transmissibility and encodes
      the viral coat protein and two non-structural proteins with molecular masses of
      29.4 kDa and 32.8 kDa. Deletions and a frameshift in the two non-structural genes
      did not interfere with encapsidation or co-replication of RNA 2 with RNA 1 after
      mechanical inoculation of plants. Mutations that affected the 29.4K gene or both
      non-structural genes abolished nematode transmission, whereas a large deletion in
      the 32.8K gene had no effect on transmission by P. pachydermus. It is concluded
      that the 29.4K gene but not the 32.8K gene is involved in transmission of isolate
      PpK20 by this vector.

PMID- 9018071
TI  - Beet soil-borne virus RNA 2: similarities and dissimilarities to the coat protein
      gene-carrying RNAs of other furoviruses.
AB  - The complete sequence of the 3454 nt of RNA 2 of the Ahlum isolate of beet soil
      borne furovirus (BSBV) has been determined starting with two short stretches of
      cloned cDNA. Unknown parts of the sequence were amplified by means of RT-PCR
      techniques using combinations of specific and random primers. BSBV RNA 2 is more
      similar in its genetic organization to potato mop top virus (PMTV) RNA 3 than to
      any other furoviral RNA, although it is more than 1100 nt longer. Its 3'-end,
      unlike that of PMTV RNA 3, has the potential to fold into a tRNA-like structure.
      It contains one large open reading frame for a readthrough protein with a
      molecular mass of 104 kDa (104K protein) which is interrupted internally by an
      amber stop codon terminating the coding region for a protein of 19 kDa (19K),
      most likely the viral coat protein (CP). The readthrough domain of the 104K
      protein is much larger than that of PMTV, but the N- and C-proximal portions of
      these domains are similar for the two viruses. No serological relationships were
      found between the particles of the two viruses, although more than 50% of the
      amino acid sequences of the putative CPs are identical.

PMID- 9018072
TI  - A DNA primer associated with banana bunchy top virus.
AB  - Banana bunchy top virus (BBTV) genomic ssDNA is capable of complementary strand
      synthesis in vitro without the addition of exogenous primers. We have
      demonstrated that the self-priming of BBTV can be attributed to a population of
      endogenous primers which are bound to the genomic DNA within the virions. The
      primer molecules appeared to be composed entirely of DNA and are heterogeneous in
      size. The primers were cloned, sequenced and shown to map to a region within the
      major common region and extend 5' of this conserved region. These primers were
      found to be associated with multiple components of the genome and were capable of
      full-length complementary strand synthesis in vitro. Interestingly, most of the
      cloned primers appeared to be derived from BBTV DNA-5; no function has yet been
      determined for the putative protein of the large ORF within this component.

PMID- 9018073
TI  - Transcriptional analysis and promoter activity of the Spodoptera littoralis
      multicapsid nucleopolyhedrovirus ecdysteroid UDP-glucosyltransferase gene.
AB  - The ecdysteroid UDP-glucosyltransferase gene (egt) of Spodoptera littoralis
      multicapsid nucleopolyhedrovirus (SpliMNPV) is a homologue of the Autographa
      californica MNPV (AcMNPV) egt gene, which has been found to block insect
      moulting. Infection of larvae with an egt-deleted AcMNPV resulted in enhanced
      mortality as compared to infection with the wild-type virus. Consequently,
      deletion of an egt gene has been proposed as a tempting approach for enhancing
      the insecticidal properties of baculoviruses. In a previous report we described
      the mapping and sequencing of the SpliMNPV egt gene. Here we use time-course
      Northern blot and biochemical analyses to show the production of egt transcripts
      and protein. The SpliMNPV egt transcription start sites were mapped to 22 and 25
      nucleotides downstream of the TATA box by primer extension. Transient expression
      assays of chimeric egt promoter-chloramphenicol acetyltransferase (cat) reporter
      gene constructs revealed low promoter activity that was transactivated by AcMNPV
      immediate-early viral protein IE-1.

PMID- 9018074
TI  - Multiple synchronous primaries of the gastrointestinal tract: a molecular case
      report.
AB  - Six synchronous gastrointestinal primaries were identified in a 70 year old male
      with no known cancer predisposition syndrome or recognized risk factors except
      alcohol abuse. These specimens appeared to be independent and unrelated by gross
      and histopathological examination. In order to further evaluate the six tumors,
      we analyzed selected DNA sequences for alterations in the K-ras oncogene and p53
      tumor suppressor gene. In addition, three loci were analyzed to determine
      microsatellite instability. Using the polymerase chain reaction, single stranded
      conformational polymorphism, and DNA sequencing, we demonstrated that each
      primary manifests genetic characteristics typical of the tissue of origin. In
      addition, one primary, a moderately differentiated colon adenocarcinoma,
      exhibited mutations not detected in the other specimens. This study suggests that
      these synchronous primaries arose independently and progressed along different
      carcinogenic pathways.

PMID- 9018075
TI  - Metabolism of carcinogenic N-nitroso-N-methylaniline by purified cytochromes P450
      2B1 and P450 2B2.
AB  - N-Nitroso-N-methylaniline (NMA) is an esophageal carcinogen in the rat. The in
      vitro enzymatic metabolism of NMA was investigated using cytochromes P450 2B1 and
      P450 2B2, isolated from liver microsomes of rats pretreated with phenobarbital
      (PB), reconstituted with NADPH-cytochrome P450 reductase and
      dilauroylphosphatidylcholine. Formaldehyde is produced by both cytochromes P450
      (P450). NMA is a better substrate for P450 2B1 than for P450 2B2. The maximal
      velocity (Vmax) values are 3.3 and 1.6 nmol HCHO/min per nmol P450 for P450 2B1
      and P450 2B2, respectively. Beside formation of formaldehyde, aniline and p
      aminophenol (p-AP) are found to be metabolites formed from NMA by both P450
      isoenzymes. P450 2B1 also affords phenol, while none was found with the P450 2B2
      isoenzyme. Phenol formation presumably arose from direct alpha-C-hydroxylation of
      NMA via a benzenediazonium ion (BDI) intermediate. The results suggest strongly
      that P450 2B1 catalyzes both alpha-C-hydroxylation and denitrosation of NMA while
      P450 2B2 catalyzes only denitrosation. Therefore, the P450 2B1 isoenzyme
      participates in the activation of NMA to the ultimate carcinogenic BDI.

PMID- 9018076
TI  - AT1 angiotensin II receptor subtype in the human larynx and squamous laryngeal
      carcinoma.
AB  - The presence of the angiotensin type 1 receptor (AT1 Ang II-R) was investigated
      in normal and diseased human larynx using a specific monoclonal antibody
      (6313/G2). When tissue AT1 content was studied by SDS electrophoresis with
      immunoblotting, the receptor was detected in 10/10 laryngeal tumours, and in 7/10
      samples of normal tissue from the same patients. Two immunostaining bands,
      approximately 75 kDa, were present in all cases. Immunocytochemistry performed on
      sections of 45 formalin-fixed, paraffin-embedded laryngeal tissue samples showed
      that the receptor was expressed in normal respiratory epithelium only in a
      perinuclear pattern, above the nucleus toward the cell apex. In addition, the
      antigen was invariably present in skeletal muscle cells and in the columnar duct
      epithelium of minor salivary glands. The secretory cells were negative, but the
      antibody stained the adjacent myoepithelial cell layer. As expected, smooth
      muscle cells of the vessel walls also expressed Ang II-R. In metaplastic
      epithelium deriving from respiratory epithelium, the receptors were distributed
      diffusely throughout the cytoplasm of basal and parabasal cells. In dysplastic
      epithelium, cells of all layers were strongly positive. Finally, squamous cell
      tumours showed varying numbers of immunoreactive cells, which stained in a
      diffuse cytoplasmic and membranous pattern. Computer-assisted image analysis of
      the stained sections showed that the positivity for Ang II-R dramatically
      increased in dysplastic and well-differentiated cancer cells (3- and 5.5-fold
      higher than in normal epithelium, respectively), but there was less in poorly and
      very poorly differentiated cancer. Receptor abundance was not correlated with
      tumour size nor lymph node involvement. These results suggest a possible role of
      Ang II in the growth or function of normal and neoplastic larynx tissue, which is
      especially significant in early neoplastic change.

PMID- 9018077
TI  - Evaluation of glycogen level in human lung carcinoma tissues by an infrared
      spectroscopic method.
AB  - Glycogen levels in the tissue samples obtained from carcinomas and normal
      sections of human lungs (26 patients) were studied by measuring the infrared band
      intensity at 1045 cm(-1) due to glycogen. As an internal standard peak, the band
      at 1545 cm(-1) (amide II) was chosen, and the ratios of these band areas
      (A1045/A1545) were compared with histological classification and differentiation
      of tumors. The glycogen level in the carcinoma tissues was significantly higher
      than that in the normal tissues (P < 0.01, n = 26). Further, the ratio of amounts
      of glycogen in the carcinomas and in the normal tissues for adenocarcinoma was
      higher than that for squamous cell carcinoma (P < 0.01). The increased degree of
      differentiation of the squamous cell carcinomas appeared to be correlated with an
      increase in the glycogen level. These results suggest that comparison of glycogen
      levels in the tumor and normal section of human lung may be used as a
      differentiating parameter for abnormality and histological classification of
      tumors. The present Fourier transform-infrared spectroscopy (FT-IR) method may
      become of wide application for studying various tissue samples.

PMID- 9018078
TI  - Characterization of normal and malignant human hepatocytes by Raman
      microspectroscopy.
AB  - Raman microspectroscopy was used to characterize normal and malignant hepatocytes
      in both cultured cells and human liver tissues. Consistent spectral changes were
      observed, including intensity increases at 1040 and 1083 cm(-1) with malignancy.
      A loss of intensity at 1241 cm(-1) was also observed in cancer cells, but was
      obscured in tissues by the overlap of a 1253 cm(-1) band, thought to originate
      from heme proteins. Normal liver tissue also differed from both the malignant
      tumor and its accompanying cirrhotic tissue at 1182 cm(-1). These results
      demonstrate the potential usefulness of Raman spectroscopy in clinical diagnosis,
      and investigations into the source of the observed spectral changes will provide
      information on the underlying mechanisms of carcinogenesis.

PMID- 9018079
TI  - Antiproliferative potency of structurally distinct dietary flavonoids on human
      colon cancer cells.
AB  - Dietary flavonoids are known to be antiproliferative and may play an important
      role in cancer chemoprevention, especially cancers of the gastrointestinal tract,
      because of a direct contact with food. This study was designed to compare the
      antiproliferative potency of several structurally distinct dietary flavonoids in
      colon cancer cells, Caco-2 and HT-29, and in rat non-transformed intestinal crypt
      cells, IEC-6. Flavonoids varied significantly in their antiproliferative potency
      depending on the structural features but the observations were consistent among
      the three cell lines studied. Of the two most potent flavonoids, quercetin and
      genistein, the effect was found to be dose-dependent and chromatin condensation,
      an indication of apoptosis, was noticed. Quercetin was found to distribute
      throughout the cell with higher amounts in the perinuclear and nucleoli areas.
      The lack of specific cell membrane enrichment by quercetin was consistent with
      its lack of effect on the transepithelial resistance. While several flavonoids
      including quercetin were found to be unstable, the chemical instability did not
      correlate with the antiproliferative potency, although it may contribute to the
      antiproliferative effect.

PMID- 9018080
TI  - Prenylation of oncogenic human PTP(CAAX) protein tyrosine phosphatases.
AB  - Many isoprenylated proteins are known to participate in signal transduction, but
      not all have been identified. Using an in vitro prenylation screen, two human
      cDNAs (PTP(CAAXI) and PTP(CAAX2)) homologous to the rat PRL-1 and human OV-1
      protein tyrosine phosphatase genes were identified. PTP(CAAXI) and PTP(CAAX2)
      were farnesylated in vitro by mammalian farnesyl:protein transferase, and epitope
      tagged PTP(CAAX2) was prenylated in epithelial cells. Overexpression of
      PTP(CAAXI) and PTP(CAAX2) in epithelial cells caused a transformed phenotype in
      culture and tumor growth in nude mice. Thus, PTP(CAAXI) and PTP(CAAX2) represent
      a novel class of isoprenylated, oncogenic protein tyrosine phosphatases.

PMID- 9018081
TI  - Enhancement by neurotensin of hepatocarcinogenesis by N-nitrosomorpholine in
      Sprague-Dawley rats.
AB  - The effect of neurotensin on hepatocarcinogenesis by N-nitrosomorpholine (NNM)
      was investigated in Sprague-Dawley rats. Rats were given drinking water
      containing NNM for 8 weeks and alternate-day injections of neurotensin from the
      beginning until the end of the experiment. Preneoplastic and neoplastic lesions
      stained for placental type glutathione-S-transferase (GST-P) were examined
      histochemically. Administration of neurotensin significantly increased the
      percentage area and the number of GST-P-positive lesions, and the labeling
      indices of pre-neoplastic lesions and adjacent liver. These findings indicate
      that neurotensin enhances hepatocarcinogenesis and that this effect may be
      related to its effect in increasing cell proliferation in preneoplastic lesions.

PMID- 9018082
TI  - Reduced glutathione and S-acetylglutathione as selective apoptosis-inducing
      agents in cancer therapy.
AB  - The effect of reduced glutathione (GSH) and S-acetylglutathione (S-acglu)
      treatment on several tumor cell lines and normal cells in vitro was investigated.
      GSH and S-acglu applied at concentrations of 1 mM and 2 mM induced apoptosis in
      malignant cells as shown by DNA-fragmentation and staining of apoptotic cells
      with 7-amino-actinomycin D while viability and growth of normal cells were not
      significantly influenced by this treatment. The results demonstrated that GSH and
      S-acglu may be selective inducers of apoptosis in malignant cells.

PMID- 9018083
TI  - Cytotoxic potential of the preparations from Solanum trilobatum and the effect of
      sobatum on tumour reduction in mice.
AB  - Plant Solanum trilobatum was washed, powdered and used for extraction. The
      lyophilized aqueous extracted portion was tested for in vitro cytotoxicity by
      tissue culture technique using L929 and Vero cells. Petroleum ether, chloroform,
      ethyl acetate and ethanol were used for extraction and the extracted portions
      were subjected to in vitro tissue culture studies. It was shown that petroleum
      ether extract induced remarkable cytotoxicity, when compared to all other
      extracts with an LD50 of 7.0 microg in L929 and 5.8 microg in Vero cells. Further
      fractionated portions of petroleum ether extract (by adsorption chromatography)
      underwent tissue culture assay, and results suggest that petroleum ether/ethyl
      acetate (75:25) extractable portion is the most active fraction, named as
      sobatum, which induced an LD50 of 7.0 microg in L929 and 7.5 microg in Vero
      cells. Sobatum significantly inhibit the peritoneal tumours induced by Dalton's
      lymphoma ascites (DLA) and Ehrlich ascites (EA) tumour cell. The effect was more
      prominent when sobatum was administered orally as evidenced from the increased
      percentage of life span. Sobatum, the partially purified portion of Solanum
      trilobatum, was again fractionated by column chromatography and all the residues
      were concentrated and crystallized from methanol, giving only one pure
      crystalline compound, that was identified as Beta-sitosterol by comparing with
      authentic sample.

PMID- 9018084
TI  - Protein tyrosine phosphatase activities are involved in apoptotic cancer cell
      death induced by GL331, a new homolog of etoposide.
AB  - GL331 is a semisynthetic topoisomerase II inhibitor derived from a plant toxin
      podophyllotoxin. In 72-h exposure assays, LD50 values of GL331 range from 0.5 to
      2 microM, which are three- to ten-fold lower than those of its homologous
      compound etoposide (VP-16), depending on different cancer cell lines including
      nasopharyngeal, hepatocellular, gastric, cervical and colon cancer types.
      Apoptotic DNA ladders could be detected when cancer cells were treated with GL331
      for 24 h even if the Bcl-2 and Bax protein levels were not altered during the
      period. Besides acting as topoisomerase II inhibitors, both GL331 and VP-16
      decrease the cellular protein tyrosine kinase (PTK) activities in cancer cells.
      The activities of protein tyrosine phosphatase (PTP) are significantly increased
      after GL331 treatment but are not affected by VP-16. GL331-induced
      internucleosomal cleavage can be efficiently prevented by two inhibitors of PTP,
      sodium orthovanadate and zinc chloride, but not by okadaic acid, which inhibits
      serine/threonine phosphatase activity. These results indicate that GL331 may
      induce apoptotic cell death, and that activation of protein tyrosine phosphatases
      may be involved in this process.

PMID- 9018085
TI  - Effects of topical treatment with fenretinide (4-HPR) and plasma vitamin A levels
      in patients with actinic keratoses.
AB  - Eighteen patients with facial actinic keratoses were treated with the retinoid
      fenretinide (4-HPR), applied topically twice-daily for 3 months. After 3 months
      of treatment, complete regression was observed in 56% and partial regression in
      44% of cases. Eight patients relapsed within 3 months after drug discontinuation.
      Six months later, only two patients (11%) showed a treatment response (complete
      regression). Blood samples showed that 4-HPR was not absorbed and no local or
      distant adverse effects were observed. Baseline plasma retinol levels were lower
      than in healthy subjects, thus suggesting that reduced retinol levels might be
      involved in this pathology. These encouraging preliminary results suggest the
      need for further studies to evaluate the best dosage schedules and duration of 4
      HPR topical application in actinic keratoses.

PMID- 9018087
TI  - Cytotoxic effect of radiolabeled C5a on U937 cells in vitro.
AB  - We studied whether the receptor (R) for C5a could be exploited to deliver the
      radiolabeled ligand into U937 cells. A dose-response for uptake of 125I-C5a was
      demonstrated. Incorporation of [3H]leucine by unstimulated or gamma-INF
      stimulated U937 cells treated with 125I-C5a, was significantly lower compared
      with cells treated with 125I alone. Trypan blue exclusion experiments indicated
      that gamma-INF stimulated cells incubated with 125I-C5a were less viable than
      cells exposed to 125I or C5a alone. The results suggest that 125I-C5a is
      internalized into myeloid cells via C5a-R and is more cytotoxic in vitro than the
      radiolabel alone, but only at/above a specific activity of 4 microCi/microg.

PMID- 9018086
TI  - Induction of iNOS mRNA by interferon-gamma in epithelial cells is associated with
      growth arrest and differentiation.
AB  - Induction of inducible nitric oxide synthase (iNOS) mRNA by interferon-gamma
      (IFNgamma) is well established in various cell types. We observed earlier that
      this induction is differentiation-dependent in human keratinocytes. Since
      IFNgamma-mediated growth arrest and differentiation are separable but
      interrelated processes in keratinocytes, iNOS might play a role in their
      regulation. We conducted a series of in vitro experiments on normal and
      transformed epithelial cells with different tissue origins. We found that
      immortalization and transformation can influence the IFNgamma-mediated iNOS
      inducibility, but this process is tissue-specific as the induction correlates
      with the ability of the cells to differentiate.

PMID- 9018088
TI  - Colon carcinogenesis in shrews by intrarectal infusion of N-methyl-N-nitrosourea.
AB  - Intrarectal infusion of a 0.15 ml solution containing 1.5 mg or 0.5 mg of N
      methyl-N-nitrosourea (MNU) was given to female shrews from 6 weeks of age.
      Fifteen shrews were given 16 doses of 1.5 mg MNU administered biweekly (group 1),
      15 shrews were given 24 doses of 0.5 mg MNU weekly (group 2), and four untreated
      shrews served as controls (group 3). Moribund shrews were killed during the
      course of the experiment and all remaining animals were killed at 37 weeks of age
      and terminated the experiment. The mean age when killed was 30.8 weeks in group 1
      and 36.2 weeks in group 2. All autopsied shrews in group 1 and group 2, 13 shrews
      each, had colon cancers, and there were a few small intestinal cancers and
      uterine squamous cell carcinomas, while no tumors were seen in the untreated
      shrews. The colonic lesions were of both exophytic and endophytic type with a
      variety of histologies and depths of invasion. Mesenteric lymph node metastasis
      was seen in 31% (4/13) of group 1 and 23% (3/13) of group 2. Thus, MNU, a
      colonotrophic carcinogen in rodents, also induced colon cancer in shrews in the
      present study.

PMID- 9018089
TI  - Apoptosis of pregnancy-dependent mammary tumor and transplantable pregnancy
      dependent mammary tumor in mice.
AB  - Pregnancy-dependent mammary tumors (PDMT) of GR/A mice and transplantable PDMT
      (TPDMT-4 line) in DDD mice, are exceptionally stable in hormone dependence,
      continue to grow until parturition and regress soon after delivery. In order to
      study the regression mechanism of PDMT and TPDMT-4, morphological and biochemical
      changes were examined in the tumors removed on day 18 (TPDMT-4) or day 20 (PDMT)
      of pregnancy, and on the expected parturient and the following postpartum days.
      DNA fragmentation occurred from day 18 (TPDMT-4) or day 20 (PDMT) of pregnancy to
      the day after parturition. Apoptotic cells were demonstrated by an in situ 3'-end
      labeling method, and the plateau of the number of apoptotic cells was observed on
      the parturient day in PDMT and on the day after parturition in TPDMT-4. Reverse
      transcriptase polymerase chain reaction showed that expression of Fas was
      slightly increased but that of bcl-2 was decreased during the process of
      involution of TPDMT-4 and PDMT. These results suggest that both an increase in
      expression of Fas and decrease in expression of bcl-2 are involved in the
      apoptosis of pregnancy-dependent mammary tumor cells after parturition.

PMID- 9018090
TI  - Micronuclei-induction and its correlation to cell survival in HeLa cells treated
      with different doses of adriamycin.
AB  - The treatment of HeLa cells with different concentrations of adriamycin (0, 5,
      10, 25, 50 and 100 microg/ml) resulted in a significant and dose-dependent
      decline in the cell survival. Conversely, the frequency of micronuclei increased
      in a concentration-dependent manner. The micronuclei-induction and cell survival
      were found to be inversely related.

PMID- 9018091
TI  - Expression of resistance-related proteins in tumoral and peritumoral tissues of
      patients with lung cancer.
AB  - Twenty tumoral and peritumoral tissues from patients with lung cancer were
      analyzed immunohistochemically for the drug resistance-related proteins P
      glycoprotein (P-170), topoisomerase II (Topo-II), glutathione S-transferase-pi
      (GST-pi), metallothionein (MT), heat shock protein-70 (HSP-70) and the putative
      regulators of resistance (ErbB1, Fos and Jun). Protein expression of Topo-II, GST
      pi, MT, HSP-70, ErbB1, Fos and Jun was elevated in tumor tissue in comparison to
      normal tissue. The different expression of the proteins between tumoral and
      normal tissues was statistically significant for Topo-II (P = 0.05), MT (P =
      0.03), and HSP-70 (P = 0.01), whereas ErbB1 showed a borderline significance. The
      expression of the proteins was frequently increased in smokers in comparison to
      non-smokers. In general, the increase of the proteins of smokers corresponded in
      tumoral and non-tumoral tissue. Different expression was only found with MT and
      HSP-70 which were higher in tissues of smokers.

PMID- 9018092
TI  - Clinical evaluation of potential usefulness of CEA, CA 15-3, and MCA in follow-up
      of breast cancer patients.
AB  - The potential usefulness of MCA, CA 15-3 and CEA in monitoring of breast cancer
      patients was evaluated in 135 female patients with histologically confirmed
      breast cancer. The patients were classified into two groups as follows: group of
      patients with no evidence of disease, NED; and group of patients with progressive
      disease, PD. In total, 2106 measurements of CEA, CA 15-3, and MCA were performed
      using an enzyme immunoassay. Serum levels of all three markers in the NED group
      differed significantly from those of patients with PD. The observed differences
      in the sensitivity and specificity of CEA, CA 15-3, and MCA tests were not
      significant. The serum concentrations of a particular marker correlated well with
      the concentrations of the other two markers, except when CEA was correlated with
      MCA or CA 15-3 in NED group patients. The elevation of tumor markers preceded by
      some 7 months the clinical evidence of dissemination, and marker levels reflected
      at a high percentage the response to therapy in PD patients. Therefore, this
      clinical study confirmed that MCA, CA 15-3 and also CEA are suited to
      discriminate between disease and disease-free periods, and also validated the
      usefulness of markers for treatment response monitoring.

PMID- 9018093
TI  - Menstrual phase and breast cancer surgery: influence on clinical outcome or
      pitfall of statistical analysis?
AB  - The influence of menstrual status at the time of surgery on the prognosis of
      women suffering from breast cancer is still discussed controversially. In our
      patient collective, including 149 patients, we obtained statistically significant
      results for six different time intervals, indicating that patients who underwent
      surgery between 11 and 22 days after the last menstrual period (LMP) have a
      poorer outcome. Focusing on the effect of statistical data evaluation strategy we
      designed a simulation study to evaluate the amount of type I error (error of a
      false positive test result) in a multiple testing situation involving a cyclical
      covariate. Accordingly, we corrected the minimum P-values for the occurring type
      I error rates. After that correction all six previously significant P-values
      failed to achieve statistical significance. The impact of different statistical
      data evaluation strategies in a multiple testing situation is discussed.

PMID- 9018094
TI  - Interferon potentiates antiproliferative activity of CPT-11 against human colon
      cancer xenografts.
AB  - We studied the antiproliferative effect of recombinant human interferon
      alpha/beta/gamma (rHuIFN-alpha/beta/gamma) and CPT-11 against human colon cancer
      xenografts in nude mice. CPT-11 (25 mg/kg) alone exhibited significant
      antiproliferative effects. Although rHuIFN-alpha/beta/gamma alone did not show
      antiproliferative activity, it markedly enhanced the antiproliferative activity
      of CPT-11. rHuIFN-alpha/beta/gamma significantly increased in the population of
      cells in the S-phase. rHuIFN-alpha/beta/gamma progressed cell cycle in the S
      phase under the existence of CPT-11, which exhibited no effect on cell cycle
      progression. Because CPT-11 is known to exhibit antiproliferative effect on S
      phase cells, IFNs, especially rHuIFN-alpha and beta, can enhance the
      antiproliferative effect of CPT-11 mediated by cell accumulation in the S-phase.

PMID- 9018095
TI  - Dose-related increases in quantitative values for altered hepatocytic foci and
      cytochrome P-450 levels in the livers of rats exposed to phenobarbital in a
      medium-term bioassay.
AB  - The dose-response relationship between liver tumor promoting activity and
      cytochrome P-450 (CYP) induction by phenobarbital sodium (PB) was investigated
      using the liver medium-term bioassay system of Ito. Two weeks after a single dose
      of N-nitrosodiethylamine (DEN) (200 mg/kg body weight, i.p.), rats were given PB
      at dietary levels of 500, 250, 125, 60, 30, 15 and 8 parts per million (ppm) for
      6 weeks. All rats were subjected to partial hepatectomy at week 3, and were
      killed at week 8. Quantitative values for glutathione S-transferase placental
      form positive hepatocytic (GST-P+) foci were increased in the high dose groups
      dose-dependently. In contrast, the values in the low dose groups were rather
      lower than that of the control. CYP2B1, 2C6 and 3A2 were predominantly
      immunostainable in hepatocytes around the central vein. While Western blotting
      revealed CYP2B1 and 2C6 proteins to be increased with strict dose-dependence,
      CYP3A2 was only elevated at high doses. Thus, a good correlation between increase
      of GST-P+ foci and CYP3A2 induction was observed, as well as with CYP2B1 and 2C6
      in high dose groups.

PMID- 9018096
TI  - Neurobiochemical changes from Taxol/Neupogen chemotherapy for metastatic breast
      carcinoma corresponds with suicidal depression.
AB  - A patient under Taxol and granulocyte colony stimulating factor (G-CSF, Neupogen)
      treatment for metastatic breast carcinoma of the liver experienced repeated
      suicidal depression on days 10 and 11 of therapy. MRI and MRS were performed
      during the fifth and sixth cycles of chemotherapy on days 1 and 10. The MRI was
      normal in all four examinations. The MRS showed normal levels of metabolites on
      days 1 of therapy, with remarkable reproducible declines in neurobiochemicals myo
      inositol (23-27%), choline (20-24%), creatine (10-14%) and glutamate/glutamine
      (22-39%) on day 10 of therapy. The neurobiochemical declines coincided with the
      patient's experience of suicidal depression. Patients reporting depression during
      standard cancer therapy may be experiencing previously undocumented
      chemotherapeutic neurobiochemical imbalances or neurotoxicity.

PMID- 9018097
TI  - Vitamin D3 reduces the apoptotic effect of IFN-gamma but does not facilitate HLA
      class II inducibility in RB-defective cells.
AB  - The retinoblastoma protein (RB) regulates the cell cycle by binding and
      inactivating the E2F transcription factors, which prevents transcription of genes
      required for DNA synthesis. RB has been shown to inhibit IFN-gamma-mediated
      apoptosis, possibly by regulating premature entry into S phase. RB is also
      required for high level IFN-gamma induction of HLA class II genes, which encode
      antigen presenting molecules, but not for other IFN-gamma inducible genes as
      demonstrated in previous reports describing the analysis of RB-transformants of
      the RB-defective cell lines, MDA-468-S4 (S4) and H2009. The IFN-gamma response of
      the HLA class II genes takes much longer than does the response of the other IFN
      gamma inducible genes, raising the question of whether RB facilitates HLA class
      II inducibility by maintaining cell viability over the long time course required
      for HLA class II induction. Thus, we sought to learn whether IFN-gamma induced
      apoptosis in an RB-defective cell line could be prevented independently of RB and
      whether doing so would facilitate HLA class II inducibility in the RB-defective
      line. Our results indicated that cotreating the RB-defective S4 cells with IFN
      gamma and Vitamin D3 decreased the number of cells containing subdiploid DNA
      compared to cells treated with IFN-gamma alone, suggesting that Vitamin D3
      reduced IFN-gamma-mediated apoptosis. S4 cells cotreated with Vitamin D3 and IFN
      gamma also had decreased cell detachment, further indicating that Vitamin D3
      decreased IFN-gamma induced apoptosis. However, Vitamin D3 cotreatment resulted
      in no detectable increase in HLA-DR, the most prominent HLA class II molecule,
      indicating that the effect of RB on HLA class II induction is not exclusively due
      to its ability to inhibit IFN-gamma induced apoptosis.

PMID- 9018098
TI  - Woodchuck p-glycoprotein found in virus-induced hepatocellular carcinomas binds
      anticancer drugs.
AB  - Virally-induced hepatocellular carcinomas (HCC) are intrinsically resistant to
      cancer chemotherapy partly due to increased expression of p-glycoprotein (pgp).
      In this study, we determined that pgp expressed in woodchuck HCC had binding
      properties were similar to the drug resistant human pgp. Pgp drug binding
      properties were characterized by photoaffinity labeling with the calcium channel
      blocker [3H]azidopine (AZD). AZD bound pgp in HCC but not in non-tumor liver
      samples, and binding was confirmed by competition with Adriamycin (IC50 = 10
      microM) and actinomycin D (IC50 = 1 microM). In summary, WHV-induced HCC
      overexpress a pgp which binds anticancer drugs suggesting a common pathway for
      drug resistance.

PMID- 9018099
TI  - 17beta-Estradiol metabolites affect some regulators of the MCF-7 cell cycle.
AB  - The activity of p34(cdc2) plays a key role in the regulation of the eukaryotic
      cell cycle. Another cell cycle associated molecule is PCNA. We investigated the
      effects of 2-hydroxy-17beta-estradiol, a cell proliferator, and 2-methoxy-17beta
      estradiol, a potent inhibitor of cell growth, on the levels and activity of
      p34(cdc2) and on the levels of PCNA, as well as on protein phosphorylation in MCF
      7 cells. 2-Hydroxyestradiol increased p34(cdc2) activity at G1/S and elevated
      PCNA levels during S-phase. 2-Methoxyestradiol caused unscheduled activation of
      p34(cdc2) in S-phase and decreased levels of p34(cdc2) and PCNA during G2/M. We
      conclude that 2-hydroxy- and 2-methoxyestradiol have definite, though different
      regulatory functions during the cell cycle.

PMID- 9018100
TI  - The role of aberrant crypt foci induced by the two heterocyclic amines 2-amino-3
      methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazo[4,5
      b]pyridine (PhIP) in the development of colon cancer in mice.
AB  - Aberrant crypt foci (ACF) have recently been identified as early putative
      preneoplastic lesions which appear in the colons of experimental animals treated
      with colon carcinogens. In a recent study the two heterocyclic amines, 2-amino-3
      methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazo[4,5
      b]pyridine (PhIP) were shown to be able to induce ACF in the colon of mice after,
      respectively, 4 and 10 weeks of exposure. In spite of the induction of ACF in
      colon of mice, IQ and PhIP have not been found to have colon as target organ in
      carcinogenicity studies. Therefore, one may question that ACF induced by IQ and
      PhIP in mice represent early stages of colon cancer. In order to investigate the
      possible role of PhIP- and IQ-induced aberrant crypt foci in the development of
      colon cancer in mice, colons from mice participating in other IQ- and PhIP
      studies of much longer duration were analyzed for ACF. The results of these
      studies showed that the number of ACF increased statistically significantly over
      time, and that the small ACF were predominant (95-100%) at all time-points. In
      conclusion, this finding suggests that the detection of a high number of ACF with
      low crypt multiplicity (1-3 AC/Focus) in mice colon after IQ- or PhIP-treatment
      is not indicative for the end-point colon cancer, and thus supports the
      hypothesis that only the presence of a high number of ACF with high crypt
      multiplicity is predictive for tumor outcome.

PMID- 9018101
TI  - Ginsenoside-Rh2 blocks the cell cycle of SK-HEP-1 cells at the G1/S boundary by
      selectively inducing the protein expression of p27kip1.
AB  - The mechanism of action by which ginsenoside-Rh2 (G-Rh2) suppresses the
      proliferation of SK-HEP-1 cells is reported. The results from flow cytometric
      analyses show that G-Rh2 arrested the cell cycle at the G1/S transition phase.
      The cyclin E-dependent kinase activity which had been immunoprecipitated with
      cyclin E-specific antibody was down-regulated in the cells in response to G-Rh2.
      The IC50 value required to down-regulate the kinase activity by 50% was
      approximately 0.75 microM. Immunoblotting analyses show that G-Rh2 selectively
      induced the expression of p27kip1 in a dose-dependent manner whereas it had no
      effect on the levels of cyclin E, cdk2, and p21WAF1. In addition, our data show
      that G-Rh2 reduced the protein levels of cdc25A at doses higher than 10 microM.
      Collectively, these data suggest that ginsenoside-Rh2 arrests the cell cycle at
      the G1/S transition phase by selectively inducing protein expression of p27Kip1
      and, as a consequence, down-regulating cyclin E-dependent kinase activity.

PMID- 9018102
TI  - Inhibition of metastasis by a dialysable factor in fetal bovine serum in B16
      melanoma cells.
AB  - Fetal bovine serum (FBS) supplemented to the culture medium inhibited the
      metastasis of B16BL6 melanoma cells in a dose-dependent manner. This metastasis
      inhibiting activity was accompanied by growth-promoting activity, up to the
      concentration of 10% FBS. However, among the clones isolated from B16BL6 cells,
      there were clones in which FBS significantly inhibited the metastasis without
      promoting their growth. Dialysis (cutoff M.W. 8000 Da) removed the metastasis
      inhibiting activity but not the growth-promoting activity from FBS. These results
      indicate that FBS has metastasis-inhibiting activity which is independent of
      growth-promoting activity, and that the metastasis-inhibiting activity is carried
      by molecules removed by dialysis.

PMID- 9018103
TI  - Insulin-like growth factor binding protein-3 in breast cyst fluid: relationships
      with insulin-like growth factors I and II and transforming growth factor-beta 1
      and 2.
AB  - Women who have palpable breast cysts with intracystic Na/K > 3 may have a lower
      risk of developing breast cancer than those with intracystic Na/K < 3. In this
      study significantly higher concentrations of insulin-like growth factor-binding
      protein-3 (IGFBP-3), insulin-like growth factors I and II (IGF-I, IGF-II) and
      transforming growth factor-beta 2 (TGF-beta2) were found in the Na/K > 3 sub
      group. No difference was found in transforming-growth factor-beta 1 (TGF-beta1)
      levels between the two sub-groups of breast cysts. A positive correlation was
      obtained for IGFBP-3 and TGF-beta1 in the Na/ K > 3 sub-group consistent with
      reports that TGF-beta1 may regulate the production of IGFBP-3. Equimolar amounts
      of total IGFs and IGFBP-3 in breast cyst fluid imply that most, if not all, of
      these IGFs are protein-bound. The significantly higher concentrations of TGF
      beta2 in the Na/K > 3 sub-group may partly explain the lower risk of breast
      cancer in this group of women.

PMID- 9018104
TI  - alpha-Adrenergic receptors may contribute to the hypertriglyceridemia associated
      with tumour growth.
AB  - The inoculation of the Yoshida AH-130 ascites hepatoma to rats resulted in an
      important loss of adipose tissue associated with a decrease in lipoprotein lipase
      (LPL) activity. Tumour burden also resulted in an important hyperlipidemia which
      affected both triglyceride and free fatty acids. Administration of phentolamine
      (an alpha-adrenergic antagonist) to tumour-bearing rats did not influence LPL
      activity, but it reversed the increase in plasma triglycerides associated with
      tumour burden. It is suggested that the hypertriglyceridemia associated with
      tumour growth may be, in part, a consequence of the effect of catecholamines on
      hepatic triglyceride secretion, via alpha-adrenergic receptors.

PMID- 9018106
TI  - Invasive pattern of lac-Z-transfected human glioblastoma cells in nude mice
      brain.
AB  - Primary, malignant brain tumors show an extensive infiltrative invasion into
      surrounding normal brain. At present, little information is available regarding
      the local invasive behavior of human brain tumors and until now no animal model
      suitable to mimic human gliomas has been reported. To identify the infiltrative
      behavior of an established glioblastoma cell line (SNB19), we achieved a stable
      transfection of the SNB19 cell line with beta-galactosidase (lac-Z) plasmid. The
      stable beta-galactosidase-expressing cells were then injected intracerebrally
      into nude mice in an attempt to follow its pattern of spread. The mice were
      sacrificed at 3, 4, and 6 weeks postinjection. We could detect tumor formation in
      all of the animals, and the tumor size increased gradually over the 6 week time
      period. Three weeks after injection, tumor cells showed characteristic
      infiltrative invasion along the corpus callosum. We also observed tumor-cell
      invasion into the anterior commissure in some animals, and each tumor cell could
      be identified by lac-Z expression as visualized by its blue color. Further
      invasion was identified at 4 and 6 weeks postinjection. Our results suggest that
      this model could be used to study the molecular mechanisms involved in the
      invasion of gliomas so that appropriate therapeutic intervention strategies could
      be designed.

PMID- 9018105
TI  - Inhibitory effects of retinoids on development of squamous metaplasia in rat
      mammary epithelial organoids cultured in Matrigel.
AB  - Squamous metaplasia (SQM) developed in cultures of rat mammary organoids in
      reconstituted basement membrane, Matrigel, under either a complete hormone medium
      (CHM) or a serum-free mammary epithelium growth medium (MEGM). Organoids cultured
      in CHM gave rise to fewer such SQM (approximately 5%) than those in MEGM
      (approximately 16%). Formation of SQM was completely suppressed when retinoids
      were added to CHM. However, a few SQM were still observed in cultures in MEGM
      with added retinoids. Addition of 5% fetal bovine serum suppressed development of
      SQM cultured in MEGM. Delayed addition of retinoids also inhibited further
      development of SQM. Development of SQM from mammary epithelial cells is not
      common, and regulatory molecules other than retinoids apparently are involved in
      their formation and prevention.

PMID- 9018107
TI  - The response of IL-3 dependent B6SUtA bone marrow cells to both erythropoietin
      and chemical inducers of differentiation.
AB  - To develop cell lines which respond to both a physiological cytokine and chemical
      agents by the induction of differentiation pathway, factor dependent B6SUtA
      murine bone marrow cells were transfected with the erythropoietin receptor
      (EpoR). Clones were obtained that exhibited different sensitivities to
      erythopoietin (Epo), with one clone exhibiting erythroid differentiation in
      response to Epo, while in another Epo acted as a proliferation stimulus.
      Moreover, parental B6SUtA cells were sensitive to the initiation of
      differentiation by butyrate, diazepam and hemin. Thus, B6SUtA cells appear to
      represent a unique model to dissect the signaling molecules involved in the
      growth and differentiation pathways employed by Epo and non-physiological
      chemicals.

PMID- 9018108
TI  - Bepridil enhances in vitro antitumor activity of antiestrogens in human brain
      tumor cells.
AB  - The possible interaction between antiestrogens (tamoxifen, clomiphene and
      nafoxidine) and bepridil, a known Na+-Ca2+ exchange blocker, in the regulation of
      cell growth was investigated using U-373 MG human astrocytoma and SK-N-MC human
      neuroblastoma cells as model cellular systems. The co-treatment of bepridil with
      antiestrogens significantly enhanced the antiestrogen-induced inhibition of the
      tumor cell growth. This bepridil-induced enhanced growth inhibition was
      significantly blocked by the addition of BAPTA/AM, an intracellular Ca2+
      chelator, implying that increased free intracellular Ca2+ concentration may be
      involved in these actions. Other Na+-Ca2+ exchange blockers such as nickel and
      benzamil, also significantly potentiated the antiestrogen-induced inhibition of
      the tumor cell growth. Taken together, the blockade of Na+-Ca2+ exchange
      mechanism by these drugs may cause prolongation of increased intracellular Ca2+
      concentration, in turn leading to these potentiated growth inhibitions of the
      tumor cells. These results suggest that the combined treatment with bepridil and
      antiestrogens may be a potential strategy for chemotherapy of brain tumors.

PMID- 9018109
TI  - Mutational specificity of the syn 1,2-dihydrodiol 3,4-epoxide of 5
      methylchrysene.
AB  - The mutational specificity of the syn dihydrodiol epoxide of 5-methylchrysene in
      the supF gene of the pSP189 vector was examined. Transversion mutations at GC
      pairs predominated with G --> T and G --> C changes accounting for 42 and 21% of
      total base change mutations. The types of mutations found reflect the previously
      determined chemical preference of this reactive species for reaction with
      deoxyguanosine residues in DNA.

PMID- 9018110
TI  - Suppression of heat-induced hsp72 accumulation by cisplatin in human glioblastoma
      cells.
AB  - The accumulation of the inducible hsp72 (72-kDa heat shock protein) after
      hyperthermia and/or cisplatin treatment in human glioblastoma cell line (A-172)
      was studied by Western blot analysis. The level of hsp72 increased to eight-fold
      10 h after hyperthermia alone (44 degrees C for 20 min, D50) and to three-fold 10
      h after cisplatin treatment (5 microg/ml) at 37 degrees C for 15 min (D50). In
      contrast, when the cells were simultaneously heated with cisplatin, the
      accumulation of hsp72 was suppressed. The level of hsp72 increased to about six
      fold and two-fold 10 h after hyperthermia (44 degrees C, 15 min) in the presence
      of 1 and 10 microg/ml (D50 or D10) of cisplatin, respectively. In addition, we
      found both the enhancement of thermosensitivity and the suppression of
      thermotolerance by the simultaneously combined treatment of hyperthermia and
      cisplatin. It has been reported that the enhancement of cisplatin cytotoxicity by
      hyperthermia is due to increase of both cisplatin uptake and DNA damage by
      hyperthermia. Our results suggest that the interactive cytotoxic enhancement by
      the combination of hyperthermia and cisplatin may be also due to the suppression
      of heat-induced hsp72 accumulation by cisplatin.

PMID- 9018111
TI  - Inhibition of the growth of WI-38 fibroblasts by benzyloxycarbonyl-Leu-Leu-Tyr
      diazomethyl ketone: evidence that cleavage of p53 by a calpain-like protease is
      necessary for G1 to S-phase transition.
AB  - The effect of a calpain-selective cell permeant inhibitor, benzyloxycarbonyl Leu
      Leu-Tyr diazomethylketone (ZLLY-CHN2), on the serum-stimulated growth of WI-38
      human fibroblasts has been investigated. Only cell permeant protease inhibitors
      with activity against calpains prevented progression into S-phase. Protein
      blotting experiments indicated that p53 immunoreactivity increased in late G1
      cells treated with ZLLY-CHN2. The content of p21Waf1/Cip1 CDK inhibitor also
      increased, providing a mechanism for the observed failure to enter S-phase.
      Further studies indicated that p53 could be degraded by a ZLLY-CHN2-sensitive
      protease immediately prior to S-phase, but that proteolysis did not occur after
      this critical time point. Chelation of extracellular Ca2+ by addition of EGTA
      inhibited the p53 degradation. Consistent with proteolysis of p53 in late G1
      phase, mu-calpain immunoreactivity transiently accumulated in cell nuclei at this
      time. ZLLY-CHN2 did not appear to increase p53 mRNA in WI-38 cells. Purified mu
      calpain required only 1 to 3 microM Ca2+ to proteolyze p53 in WI-38 cell lysates.
      These results indicate that ZLLY-CHN2 inhibits progression of WI-38 cells into S
      phase by inactivating a calpain-like protease that is responsible for proteolysis
      of constitutively expressed p53 in late G1.

PMID- 9018112
TI  - Distinct biological properties of two RET isoforms activated by MEN 2A and MEN 2B
      mutations.
AB  - Germline mutations of the RET proto-oncogene, which codes for a receptor tyrosine
      kinase, cause multiple endocrine neoplasia type 2A (MEN 2A) and 2B (MEN 2B) and
      familial medullary thyroid carcinoma (FMTC). MEN 2 mutations have been shown to
      result in RET oncogenic activation. The RET gene encodes several isoforms whose
      biological properties, when altered by MEN 2 mutations, have not been thoroughly
      addressed yet. In this study, we have introduced a MEN 2A mutation (Cys634-->Arg)
      and the unique MEN 2B mutation (Met918-->Thr) in two RET isoforms of 1114 and
      1072 amino acids which differ in the carboxy-terminus part. Herein, we report
      that each RET isoform activated by MEN 2A or MEN 2B mutation was transforming in
      fibroblasts and induced neuronal differentiation of pheochromocytoma PC12 cells.
      However, among the different RET-MEN 2 mutants, the long RET isoform activated by
      the MEN 2B mutation stimulated the most prominent neurite outgrowth in PC12
      cells, while the short RET isoform counterpart elicited a very weak
      differentiation effect in PC12 cells. We further demonstrate that the
      morphological changes of PC12 cells caused by constitutively activated RET
      oncoproteins involved the engagement of a Ras-dependent pathway. These findings
      provide evidence that the biological properties of RET-MEN 2 mutants depend on
      the interplay between the RET isoforms and the nature of the activating MEN 2
      mutation.

PMID- 9018113
TI  - Cell cycle arrest defect in Li-Fraumeni Syndrome: a mechanism of cancer
      predisposition?
AB  - Cancer predisposition in approximately 60% of Li-Fraumeni Syndrome (LFS) families
      is associated with germline mutation of the TP53 gene. The p53 protein has been
      shown to mediate G1 arrest following DNA damage. We have investigated gamma
      irradiation-induced transient and permanent G1 arrest in normal and LFS
      fibroblasts. The duration of transient G1 arrest varied between strains, but
      there was no difference in the range between normal (2-12 h) and LFS (1-13 h)
      cells. However, the extent of permanent G1 arrest was greatly reduced in LFS
      fibroblasts (mean 33+/-8% of the cell population) compared with normals (mean
      67+/-9%) and correlated with their increased radiation survival (r=0.97,
      P<0.001). This phenotype was observed in LFS fibroblasts both with (seven cases)
      and without (two cases) TP53 mutation. Parallel studies with fibroblasts derived
      from cancer-prone, p53-deficient mice revealed no radiation-induced G1 cell cycle
      arrest in p53 null (-/-) cells. The p53 +/- cells were comparable to the wt p53
      cells in transient G1 arrest capacity, but showed a diminished permanent G1
      arrest. These data clearly implicate p53 function in permanent G1 arrest. The
      reduced capacity for DNA damage-induced, permanent G1 arrest in LFS may
      contribute significantly to cancer predisposition in this familial syndrome.

PMID- 9018114
TI  - A role for epidermal growth factor receptor, c-Src and focal adhesion kinase in
      an in vitro model for the progression of colon cancer.
AB  - We have examined the function of the epidermal growth factor (EGF) receptor, c
      Src and focal adhesion kinase (FAK) in the progression of colon cancer using an
      in vitro progression model. A non-tumorigenic cell line was derived from a
      premalignant colonic adenoma (PC/AA) from which a clonogenic variant was
      established (AA/C1). Following sequential treatment with sodium butyrate and the
      carcinogen N-methyl-N'-nitro-N-nitro-soguanidine an anchorage-independent line
      was isolated which, with time in culture, became tumorigenic when injected into
      athymic nude mice (AA/C1/SB10). We have shown that both EGF receptor and FAK
      protein levels were elevated in the carcinoma cells as compared to the adenoma
      cells, while the expression and activity of c-Src were unaltered during the
      adenoma to carcinoma transition. EGF induced the movement of the carcinoma cells
      into a reconstituted basement membrane which was not seen with the premalignant
      adenoma cells. This increased motility was accompanied by an EGF-induced increase
      in c-Src kinase activity, relocalisation of c-Src to the cell periphery and
      phosphorylation of FAK in the carcinoma cells but not in the adenoma cells. This
      suggests that c-Src plays a role in the biological behaviour of colonic carcinoma
      cells induced by migratory factors such as EGF, perhaps acting in conjunction
      with FAK to regulate focal adhesion turnover and tumour cell motility.
      Furthermore, although c-Src has been implicated in colonic tumour progression, we
      demonstrate here that in the adenoma to carcinoma in vitro model c-Src is not the
      driving force for this progression but co-operates with other molecules in
      carcinoma development.

PMID- 9018115
TI  - Deregulation of cyclin E and D1 in breast cancer is associated with inactivation
      of the retinoblastoma protein.
AB  - Inactivation of the retinoblastoma protein (pRB) by mutations or abnormal
      phosphorylation is a mechanism by which tumour cells can subdue normal growth
      control. Among molecules involved in control of pRB phosphorylation, cyclin D1
      and E have been found to be deregulated and overexpressed in various types of
      cancers. In order to study the cell cycle regulatory mechanisms in breast cancer,
      we have analysed the protein expression of cyclin D1 and E in 114 tumour
      specimens from patients with primary breast cancer using Western blotting. Twenty
      five out of 34 tumours with overexpression of cyclin E showed uniform low cyclin
      D1 expression, and by immunohistochemical analysis of pRB we present evidence for
      the existence of pRB defects in approximately 40% of these tumours in contrast to
      no pRB defects in the other group of tumours. This result was supported by a high
      protein expression of the cyclin-dependent kinase inhibitor p16 in 44% of the
      tumours with high cyclin E and low D1 expression, and all immunohistochemical pRB
      defect tumours showed a high p16 protein level. Additionally, an abnormal low pRB
      phosphorylation in relation to a high proliferative activity and loss of
      heterozygosity of the retinoblastoma susceptibility gene locus were found in all
      but one tumour with immunohistochemical defect pRB. Interestingly, tumours with
      high cyclin E and low D1 expression were generally oestrogen receptor negative
      suggesting a role for cell cycle regulators in the mechanisms leading to
      oestrogen independent tumour growth. Furthermore, the prognosis differed markedly
      for the patients in the various groups of tumours, indicating that the
      heterogeneous nature of breast cancer pathogenesis and the clinical course in
      part could be explained by different and distinctive sets of cell cycle defects.

PMID- 9018116
TI  - Geranylgeraniol potentiates lovastatin inhibition of oncogenic H-Ras processing
      and signaling while preventing cytotoxicity.
AB  - Oncogenic H-Ras requires farnesylation for its transforming activity. Lovastatin
      inhibits both protein farnesylation and geranylgeranylation by decreasing
      cellular pools of farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate
      (GGPP), respectively. Use of lovastatin as a chemotherapeutic agent has been
      precluded by its significant cytotoxic effects. In this report, we describe a
      novel approach utilizing a combination of lovastatin and geranylgeraniol (GGOH)
      to potentiate the ability of lovastatin to block oncogenic H-Ras signaling and
      concomitantly rescue lovastatin toxicity. GGOH co-treatment with lovastatin
      enhances inhibition of oncogenic H-Ras processing and constitutive activation of
      mitogen-activated protein kinase (MAPK), and preserves the processing of
      geranylgeranyltransferase (GGTase) I and GGTase II protein substrates. Moreover,
      co-treatment with GGOH significantly (15-fold) attenuates the cytotoxic effects
      of lovastatin as well as prevents lovastatin-induced cell rounding. These results
      demonstrate that GGOH potentiates the anti-oncogenic/anti-signaling activity of
      lovastatin while antagonizing its cytotoxicity. These opposing effects are due to
      a GGOH metabolite that serves simultaneously as a potent inhibitor for
      farneslyltransferase as well as a substrate for GGTases I and II.

PMID- 9018117
TI  - SEN6, a locus for SV40-mediated immortalization of human cells, maps to 6q26-27.
AB  - Normal cells show a limited lifespan in culture and the phenotype of cellular
      senescence. Tumors and tumor cell lines have typically overcome this form of
      growth suppression and grow continuously as immortal cell lines in culture. We
      have exploited the DNA virus SV40 to study the mechanism by which human
      fibroblasts overcome senescence and become immortal. Multiple steps have now been
      identified, including inactivation of cellular growth suppressors through direct
      interaction with SV40 large T antigen and through mutation of a gene on
      chromosome 6 (designated SEN6). In this study, we sublocalize the site of SEN6 to
      6q26-27 based on molecular genetic analysis. Twelve SV40-immortalized fibroblast
      cell lines share a deletion in this area based on assessment for loss of
      heterozygostiy (LOH) for seven informative markers on 6q. Two immortal cell lines
      (AR5 and HALneo) appeared to have retained separate single copies of chromosome 6
      despite the fact that they are both derived from the same preimmortal SV40
      transformant and should share the same mutated allele of SEN6 (Hubbard-Smith et
      al., 1992). Detailed analysis by polymerase chain reaction, restriction fragment
      length polymorphism and fluorescence in situ hybridization shows, however, that
      although they differ for 17 markers from the centromere to 6q26, they share AR5
      derived sequences (eight markers) distal to 6q26 including the minimal deletion
      region, further supporting the assignment of SEN6 to this region. Since human
      tumors including non-Hodgkins lymphoma, mammary carcinoma and ovarian carcinoma
      show LOH in 6q26-27, inactivation of SEN6 may be responsible for immortalization
      of these tumors as well.

PMID- 9018118
TI  - Decreased expression of keratinocyte growth factor receptor in a subset of human
      transitional cell bladder carcinomas.
AB  - Growth factors and growth factor receptors are involved in tumor progression. The
      fibroblast growth factor receptor 2 gene encodes distinct isoforms. The isoforms
      which bind KGF (keratinocyte growth factor or FGF-7) are called KGF-R or FGFR2b.
      KGF-R is expressed in different epithelia and is involved in the control of
      epithelial-mesenchymal interactions. Expression of KGF-R mRNA was examined in
      normal human bladder and transitional cell carcinoma of the bladder (TCC) by semi
      quantitative RT-PCR using TFIID and GAPDH as internal standards. In normal
      bladder, the KGF-R mRNA was detected in the urothelium but not in the underlying
      stroma. In TCCs, the level of KGF-R mRNA was generally either normal or low.
      Eighteen out of 54 TCCs had a KGF-R mRNA level below 30% of that found in normal
      urothelium. This decrease in KGF-R mRNA was not accompanied by an increase in BEK
      (FGFR2c) mRNA, the other major splice variant of the fibroblast growth factor
      receptor 2 gene. Expression of the KGF-R was also monitored by
      immunohistochemistry using a functional KGF-immunoglobulin chimera. The receptor
      was uniformly expressed throughout the normal urothelium except for the umbrella
      cells. Immunoreactivity for KGF-R was found to be negative in tumors with low
      levels of KGF-R mRNA, while the peritumoral normal urothelium was positive. Among
      patients with muscle invasive tumors, those exhibiting a low level of KGF-R mRNA
      had a significantly higher proportion of cancer deaths. Our results suggest that
      decreased expression of KGF-R can be considered as a marker of tumor progression
      in muscle invasive TCCs.

PMID- 9018119
TI  - Expression of antisense RNA to S100A4 gene encoding an S100-related calcium
      binding protein suppresses metastatic potential of high-metastatic Lewis lung
      carcinoma cells.
AB  - S100A4 (also known as pEL98/mts1/p9Ka/18A2/42A/calvasculin /FSP1/CAPL), a member
      of S100-related calcium-binding proteins, has been implicated to play a role in
      metastasis. In the present study, we examined the effect of antisense S100A4 RNA
      on metastatic potential of Lewis lung carcinoma (LLC) cells. High-metastatic All
      cells were transfected with the expression vector containing S100A4 cDNA in an
      inverted (antisense) orientation under the transcriptional control of the mouse
      metallothionein promoter. Treatment of a stably transfected clone (AS10 cells)
      with Zn2+ resulted in the suppression of the experimental metastatic ability,
      which was accompanied with the expression of antisense S100A4 RNA and the
      suppression of the S100A4 expression at both the mRNA and the protein levels. To
      further confirm the effect of antisense S100A4 RNA, we established several clones
      after retroviral transduction with an antisense S100A4 construct. Notably,
      reduced metastatic potential was also evident in these clones. In the antisense
      S100A4 RNA-expressing cells, cell motility and in vitro invasiveness were found
      to be suppressed.

PMID- 9018120
TI  - Loss of heterozygosity in human breast carcinomas in the ataxia telangiectasia,
      Cowden disease and BRCA1 gene regions.
AB  - To appreciate the involvement of known or potential susceptibility genes in
      sporadic breast tumors, we have searched for chromosomal deletions by studying
      loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human
      chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast
      carcinoma with particular emphasis on specific regions. No site of consistent LOH
      was identified on chromosome 10. Five regions of LOH were contained within bands
      q22-24 of chromosome 11 for which nearly 50% of the tumors had LOH at at least
      one marker. This region is thus a major site of deletion in breast cancer and
      several tumor suppressor genes seem to be involved. One of them may be the ataxia
      telangiectasia (ATM) gene which is located in one of the affected regions. Five
      regions of LOH, one of which is within the BRCA1 gene area, were recognized along
      chromosome 17. LOH at three of these regions were found in highly proliferative
      tumors. When combined with a previous study of chromosome 13 with emphasis on
      BRCA2 and Rb1 genes, this work allowed to distinguish a total of 12 regions of
      LOH, variably affected in breast tumors and correlated with prognostic
      parameters.

PMID- 9018121
TI  - The TEL gene products: nuclear phosphoproteins with DNA binding properties.
AB  - The human TEL gene is involved in several 12p13 chromosomal abnormalities present
      in various human hematological malignancies, the most frequent being the
      t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia. The
      predicted product of TEL harbours an amino acid region similar to the ETS DNA
      binding domain. We now report the isolation of the murine TEL cDNA and the
      characterization of the human TEL proteins. Human and murine TEL proteins are
      particularly homologous within their aminoterminal regions and their ETS domains.
      TEL proteins are nuclear and display specific DNA binding activity toward
      classical ETS binding sites. In addition, we show that TEL mRNAs initiate
      translation at either of the two first inframe ATGs (codon 1 and 43) to encode 50
      kDa and 57 kDa TEL proteins. In vivo, each of these primary translational
      products is modified by multiple phosphorylation events.

PMID- 9018123
TI  - Deletion mapping of chromosome 4 in head and neck squamous cell carcinoma.
AB  - Genomic deletions involving chromosome 4 have recently been implicated in several
      human cancers. To identify and characterize genetic events associated with the
      development of head and neck squamous cell carcinoma (HNSCC), a fine mapping of
      allelic losses associated with chromosome 4 was performed on DNA isolated from 27
      matched primary tumor specimens and normal tissues. Loss of heterozygosity (LOH)
      of at least one chromosome 4 polymorphic allele was seen in the majority of
      tumors (92%). Allelic deletions were confined to short arm loci in four tumors
      and to the long arm loci in 12 tumors, suggesting the presence of two regions of
      common deletion. One region of frequent deletion was centered at D4S405 on 4p and
      included the loci D4S1546 to D4S428 in approximately 41% of the tumors. The
      common region of deletion on 4q was more complex and extended from D4S1571 to
      D4S1573. Frequent genetic alterations were observed within this region (4q25) and
      one marker, D4S407, exhibited a high frequency of LOH (>75%). These results
      indicate that alterations of chromosome 4 regions are associated with HNSCC
      tumorigenesis and further localizes the regions that may harbor tumor suppressor
      genes.

PMID- 9018122
TI  - Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant
      transforming activity and its protein binds to p53.
AB  - The 357 amino acid open reading frame 1 (ORF-1), also designated DR7, within the
      SalI-L fragment of human herpesvirus 6 (HHV-6) exhibited transactivation of the
      human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter
      and increased HIV-1 replication (Kashanchi et al., Virology, 201, 95-106, 1994).
      In the current study, the SalI-L transforming region was localized to the SalI-L
      SH subfragment. Several ORFs identified in SalI-L-SH by sequence analysis were
      cloned into a selectable mammalian expression vector, pBK-CMV. Only pBK/ORF1
      transformed NIH3T3 cells. Furthermore, cells expressing ORF-1 protein produced
      fibrosarcomas when injected into nude mice, whereas control cells, expressing
      either no ORF-1 protein or C-terminal truncated (after residue 172) ORF-1
      protein, were not tumorigenic. Western blot analysis of proteins extracted from
      the tumors revealed ORF-1 protein. Additional studies indicated that ORF-1 was
      expressed in HHV-6-infected human T-cells by 18 h. Co-immunoprecipitation
      experiments showed that ORF-1 protein bound to tumor suppressor protein p53, and
      the ORF-1 binding domain on p53 was located between residues 28 and 187 of p53,
      overlapping with the specific DNA binding domain. Functional studies showed that
      p53-activated transcription was inhibited in ORF-1, but not in truncated ORF-1,
      expressing cells. Importantly, the truncated ORF-1 mutant also failed to cause
      transformation. Analysis of several human tumors by PCR revealed ORF-1 DNA
      sequences in some angioimmunoblastic lymphadenopathies, Hodgkin's and non
      Hodgkin's lymphomas and glioblastomas. The detection of ORF-1 sequences in human
      tumors, while not proof per se, is a prerequisite for establishing its role in
      tumor development. Taken together, the results demonstrate that ORF-1 is an HHV-6
      oncogene that binds to and affects p53. The identification of both transforming
      and transactivating activities within ORF-1 is a characteristic of other viral
      oncogenes and is the first reported for HHV-6.

PMID- 9018124
TI  - Allelic loss determination in chronic lymphocytic leukemia by immunomagnetic bead
      sorting and microsatellite marker analysis.
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the
      western world. Details of the molecular mechanisms involved in the pathogenesis
      of this leukemia are unclear at present. In other malignancies tumorigenesis has
      been shown to proceed via a multistep progression model with a causal relation
      between the accumulation of genetic abnormalities and more aggressive clinical
      behavior. The loss of chromosomal segments in malignant cells has proven useful
      in mapping regions of DNA that contain candidate tumor suppressor genes. The
      detection of loss of heterozygosity (LOH) has been greatly facilitated by the
      analysis of highly polymorphic microsatellite markers enabling the identification
      of submicroscopic losses. Utilizing immunomagnetic bead sorting to separate
      leukemic from normal cells we identified at least one allelic losses in 8/29
      (28%) of analysed CLL cases with a PCR-based assay. On chromosomal arm 3p we have
      identified homozygous deletions in 3/29 cases at locus D3S1284 residing in the
      vicinity of the newly described FHIT gene. Several cases of CLL manifested LOH at
      a locus telomeric to the p15 and p16 tumor suppressor genes, all being early to
      intermediate stage disease. Our findings suggest that losses at these loci may
      contribute to the development and/or progression of CLL in at least a subset of
      cases.

PMID- 9018125
TI  - Induction of apoptosis in human lung cancer cells after wild-type p53 activation
      by methoxyestradiol.
AB  - 2-Methoxyestradiol (2-MeOE2) treatment caused significant growth inhibition of
      H460 and A549 human lung cancer cell lines which contain wild-type p53. However,
      2-MeOE2 had a little effect on the p53 negative H358 and p53 mutated H322 cell
      lines. Western blot analysis indicated that 2-MeOE2 treatment resulted in an
      eightfold increase in the endogenous wild-type p53 protein, while the level of
      the mutant p53 protein remained unchanged. TdT staining indicated that following
      2-MeOE2-mediated increases in wildtype p53 protein, cells bypass the G1-S
      checkpoint of the cell cycle with 30 to 40% undergoing apoptosis. Introduction of
      anti-sense wt-p53 into wt-p53 cells abrogated the 2-MeOE2 effect. A significant
      portion of lung cancer retains the wild-type p53 gene therefore, 2-MeOE2 may have
      therapeutic application.

PMID- 9018126
TI  - DNA tumor viruses and Src family tyrosine kinases, an intimate relationship.

PMID- 9018127
TI  - Analysis of the contributions of the equine herpesvirus 1 glycoprotein gB homolog
      to virus entry and direct cell-to-cell spread.
AB  - Experiments to analyze the functions of the equine herpesvirus 1 (EHV-1)
      glycoprotein gB were performed. Cell lines which stably expressed either the full
      length EHV-1 gB or only the extracellular portion of gB (amino acids 1 to 844)
      were constructed and were termed TCgBf and TCgB delta, respectively. Using the
      cell line TCgBf, a gB-negative viral mutant, L11delta gB, was generated by
      replacing a 2.1-kb BglII-NruI fragment in the EHV-1 strain RacL11 gB with the
      Escherichia coli LacZ gene. EHV-1 strain RacL11, the modified live vaccine strain
      RacH, and L11delta gB were used for functional studies. It was shown that: (i)
      EHV-1 gB is essential for virus growth in vitro since gB-negative L11delta gB
      exhibited titers of <10 PFU/ml when grown and titrated on noncomplementing cells.
      (ii) The cell line expressing truncated gB (TCgB delta) did not complement for
      the growth of L11delta gB, but the RacH virus grew to titers comparable to those
      of RacL11 in all cell lines tested. Since RacH had amino acids 944-980 of gB
      replaced by 7 missense amino acids as determined by nucleotide sequence analysis,
      the extreme carboxyterminus but not a domain between amino acid residues 845 and
      943, probably the transmembrane domain, of EHV-1 gB is dispensable for virus
      growth in cultured cells. (iii) Single infected cells but no plaque formation
      were observed after infection of noncomplementing cells with L11delta gB,
      demonstrating the requirement of EHV-1 gB for direct cell-to-cell spread of
      infection. (iv) The attachment of gB-negative L11delta gB virions to target cells
      was similar to both phenotypically complemented L11delta gB and parent RacL11
      virus. (v) L11delta gB viral titers could be enhanced by using the fusogen
      polyethylene glycol (PEG). The increase of L11delta gB titers by PEG treatment,
      however, was considerably lower compared to gB-negative pseudorabies virus,
      suggesting that EHV-1 gB might not be as stringently required for virus
      penetration as are its homologs in other Alphaherpesvirinae.

PMID- 9018128
TI  - Adenovirus E1B 19K protein is required for efficient DNA replication in U937
      cells.
AB  - The adenovirus E1B 19K gene plays an essential role in transformation of primary
      rodent cells in cooperation with E1A and in the inhibition of apoptosis during
      lytic infection. It has been shown that this E1B 19K protein is not necessary for
      viral DNA replication in human cell lines, such as HeLa and KB. We reported here
      that the E1B 19K mutant viruses were unable to replicate efficiently in a
      monocyte cell line, U937. Viral DNA synthesis and late gene expression were found
      to be defective in U937 cells infected with E1B 19K mutants compared with wild
      type virus. Early viral RNA splicing patterns also differ between wild-type and
      dl337-infected cells. Furthermore, the defect in viral replication could be
      complemented by dl312 virus defective in E1A expression 4 days after infection
      with E1B mutants, suggesting persistence of the E1B mutant genome in the infected
      cells despite defective onset of the late phase of replication. These results
      imply that E1B 19K is required for efficient viral DNA replication in U937 cells.
      Inefficient DNA replication is also found in another monocyte cell line, THP-1.

PMID- 9018129
TI  - Analysis of mutations within the cytoplasmic domain of the Moloney murine
      leukemia virus transmembrane protein.
AB  - The role of the cytoplasmic tail of the Moloney murine leukemia virus
      transmembrane protein in the regulation of syncytia was examined. Three mutations
      within the cytoplasmic tail were studied. Linker-insertion in7705-12a is within
      the viral-associated cytoplasmic tail, linker-insertion in7748-12a is within the
      R peptide, and a third mutation expresses TM lacking the R peptide (Env R-). The
      Env R- construct was nonviable in Rat1 cells, however, rapidly reverted to a form
      containing the R peptide when passaged in NIH/3T3 cells. in7705-12a was
      temperature-sensitive in Rat1 cells, as previously characterized, but was viable
      at either temperature in NIH/3T3 cells. in7748-12a was comparable with wild-type
      M-MuLV. The ability of the env constructs to form large multinucleated syncytia
      with NIH/3T3 and XC cells were examined using transient expression assays,
      eliminating reversion events due to viral passage and reverse transcription. The
      Env R- constructs formed syncytia with NIH/3T3 cells. in7705-12a displays
      enhanced proteolytic cleavage of the R peptide. Neither linker-insertion mutation
      in7705-12a or in7748-12a activated fusion with NIH/3T3, despite the abundance of
      processed TM with in7705-12a. All three mutants were fusion competent with Rat XC
      cells, even in the absence of any cleavage of the R peptide. These results
      provide insights regarding steric and the temporal affects of cleavage of the R
      peptide and the assembly of a fusion competent oligomer.

PMID- 9018130
TI  - Recombinant measles viruses defective for RNA editing and V protein synthesis are
      viable in cultured cells.
AB  - The measles virus (MV) phosphoprotein (P) gene encodes three proteins, P, C, and
      V. The V protein is synthesized by pseudo-templated transcription, also
      designated as RNA editing: during P gene transcription one G residue is inserted
      at a defined position in about 50% of the mRNAs. To study the importance of
      sequence elements for the nontemplated G insertion, we generated recombinant MVs
      in which six different mutations were introduced within the region where editing
      occurs (3' UUUUUCCC, template strand). These viruses were then analyzed for their
      ability to edit their P mRNA and to produce V protein. Single U to C changes
      within the U stretch abolished editing. Extending the template by three C
      residues at the site of G insertion resulted in a less precise editing phenotype
      and overproduction of V. None of these mutants were impaired in their
      multiplication behavior when analyzed in cultured cells. However, the syncytia of
      a recombinant MV overproducing V protein were in general smaller and lysed 1 to 2
      days later than usual.

PMID- 9018131
TI  - Characterization of proteins binding to the ZII element in the Epstein-Barr virus
      BZLF1 promoter: transactivation by ATF1.
AB  - Previous studies have shown that the ZII element in the BZLF1 promoter (P1) is
      responsive to TPA and anti-immunoglobulin induction. In this report, we have
      studied the DNA/protein complexes formed when ZII is used as a binding site.
      Twelve distinct DNA/protein complexes were seen in mobility shift experiments
      using Akata cell nuclear extracts and radiolabeled ZII. Eleven of these complexes
      were also formed when either BJAB or Raji cell nuclear extracts were used in the
      binding reaction. Six DNA/protein complexes were affected by mutations in the
      core TGACATCA motif of ZII which abolish responsiveness to TPA, anti
      immunoglobulin treatment, and HHV6 transactivation. The relative sizes of the
      proteins in the DNA/protein complexes were determined by UV crosslinking. Four
      distinct specific binding proteins affected by core mutations in ZII were
      identified as ATFa, ATF1, ATF2, and c-jun. Overexpression of ATF1 in
      cotransfection experiments caused transactivation of the wild-type P1 promoter
      but had no effect on a promoter containing a mutant ZII element. An ATF1 mutant
      with a deleted DNA binding domain failed to transactivate P1. Overexpression of c
      jun, ATFa, or ATF2 had no effect on the wild-type or mutant P1 promoter. Our
      results suggest that ATF1 interacts with the ZII element and may be involved in
      Epstein-Barr virus reactivation.

PMID- 9018132
TI  - Activation of collagenase IV gene expression and enzymatic activity by the
      Moloney murine leukemia virus long terminal repeat.
AB  - Moloney murine leukemia virus (Mo-MuLV) is a thymotropic and leukemogenic
      retrovirus which causes T lymphomas and leukemias, yet does not contain a
      transforming gene product. Mo-MuLV has been shown to trans-activate cellular
      genes via a polymerase III-generated transcript, designated let, from the long
      terminal repeat (LTR). Here we demonstrate that introduction of the Mo-MuLV LTR
      stably, or transiently, into murine or human cultured cells resulted in an 8- to
      15-fold increase in collagenase IV (92-kDa gelatinase, gelatinase B, matrix
      metalloproteinase-9) gene expression. Collagenase IV protein expression was
      induced 9-fold by stable integration of MuLV LTR, as measured by immunoblot
      analysis using an anti-collagenase IV polyclonal antibody. The MuLV LTR
      coordinately stimulated the proteolytic activity of collagenase IV by 14-fold.
      The AP-1-binding site in the collagenase IV promoter was required for
      transactivation by the LTR. Collagenase type IV degrades type IV collagen, a
      major component of basement membrane, which constitutes the first step of the
      metastatic cascade. The activation of proteolytic enzymes by the MuLV LTR may
      thus play a contributory role in the development or spread of virus-induced
      lymphomas or leukemias.

PMID- 9018133
TI  - Molecular characterization and baculovirus expression of the glycoprotein B of a
      seal herpesvirus (phocid herpesvirus-1).
AB  - A glycoprotein B (gB) gene homologue was identified in a 5.4-kb BamHl genomic
      fragment of the phocid herpesvirus type-1 (PhHV-1) which represents a widespread
      and important pathogen of pinnipeds. Sequence analysis revealed a gB-specific
      open-reading frame comprising 881 amino acids. Phylogenetic analysis gave
      evidence for a close evolutionary relationship between PhHV-1 and members of the
      Varicellovirus genus of the alpha-Herpesvirinae and canid herpesvirus in
      particular. In PhHV-1-infected Crandell feline kidney cells gB is expressed as a
      113-kDa glycosylated molecule which is proteolytically cleaved into at least two
      fragments of 67 and 53-59 kDa apparently forming disulfide-linked heterodimers of
      140 kDa. Cell surface expression of PhHV-1 gB was confirmed by FACS analysis.
      Thus, synthesis and processing of the gB protein of PhHV-1 follows a pattern also
      observed in other Varicelloviruses. Since the gB protein of herpesviruses,
      expressed in the baculovirus system, has been shown to be a suitable target for
      vaccine design, we used this system for expression of PhHV-1 gB. Recombinant
      (rec) baculovirus-expressed gB was identified as a 105-kDa glycosylated molecule.
      Proteolytic cleavage into fragments of 62 and 52 kDa was markedly delayed
      compared to wild-type (wt) gB. Wt and rec gB harbored endoglycosidase H
      (precursor)- as well as N-glycosidase F-sensitive N-glycans (proteolytic
      fragments). Baculovirus-expressed gB appeared to be antigenically authentic,
      since it was recognized in radioimmunoprecipitation and immune peroxidase
      monolayer assays by PhHV-1-neutralizing seal sera and by gB-specific neutralizing
      murine monoclonal antibodies. Furthermore, PhHV-1-neutralizing antibodies were
      induced in mice following immunization with baculovirus-expressed gB, indicating
      its suitability for incorporation in a candidate vaccine for seals.

PMID- 9018134
TI  - Poxvirus-based Japanese encephalitis vaccine candidates induce JE virus-specific
      CD8+ cytotoxic T lymphocytes in mice.
AB  - Recombinant Japanese encephalitis (JE) vaccine candidates based on a highly
      attenuated vaccinia virus (NYVAC-JEV) and a canarypox virus (ALVAC-JEV) were
      evaluated for their ability to induce specific antibodies and cytotoxic T
      lymphocytes (CTLs) in mice. Six- to eight-week-old male Balb/c mice that received
      one or two intraperitoneal inoculations with these JE vaccine candidates at a
      dose of 1 x 10(7) PFU per mouse produced neutralizing antibody and antibodies to
      the envelope (E) and nonstructural 1 (NS1) proteins as determined by
      radioimmunoprecipitation. Immunization with either of these vaccine candidates
      also induced JE virus-specific T lymphocytes that proliferated in response to
      stimulation with infectious virus and/or noninfectious viral antigens. Mice
      maintained detectable levels of neutralizing antibody and JE virus-specific
      memory T cells for at least 6 months after immunization with NYVAC-JEV and for 4
      months after immunization with ALVAC-JEV. Cells induced to proliferate after
      stimulation with live virus contained specific CD8+ CTLs that lysed primary
      Balb/c mouse kidney cells infected with JE virus and P815 mastocytoma cells
      infected with a recombinant vaccinia virus expressing the premembrane (prM), E,
      and NS1 proteins. These CTLs also lysed P815 cells infected with vaccinia
      recombinants expressing prM and E, and those expressing E and NS1, but did not
      lyse P815 cells infected with a recombinant virus expressing only NS1, indicating
      that the CTLs mainly recognized E, but did not recognize NS1. These results
      demonstrate that both recombinant JE vaccines, NYVAC-JEV and ALVAC-JEV, induce JE
      virus-specific antibody and CTLs in mice.

PMID- 9018135
TI  - Complementation of and interference with Sindbis virus replication by full-length
      and deleted forms of the nonstructural protein, nsP1, expressed in stable
      transfectants of Hela cells.
AB  - Stable transfectants of Hela cells were isolated which expressed either the full
      length 540-amino-acid Sindbis virus (SV) nonstructural protein, nsP1 (the form
      encoded by the mutant, SV(LM21)), or one of four forms with a carboxyl-terminal
      deletion. SV(LM21), in contrast to standard SV (SV(STD)), can replicate in Hela
      cells maintained in low-methionine (LM) medium. Expression of full-length nsP1(1
      540), nsP1(1-492), or nsP1(1-448) resulted in complementation of SV(STD) when
      infected Hela cells were kept in LM medium after infection. In contrast, when
      cells were infected with SV(LM21) and maintained in LM medium, stable expression
      of any of the deleted forms of nsP1 interfered with the replication of virus. The
      ability of "cellular" nsP1 to complement SV(STD) in LM medium correlated with its
      methyltransferase activity.

PMID- 9018136
TI  - Genetic analysis of the phi X174 DNA binding protein.
AB  - The phi X174 J protein is 37 amino acids in length and contains 12 basic
      residues. There are no acidic amino acids in the protein. The basic residues are
      concentrated in two clusters in the N-terminus which are separated by a proline
      rich region. To investigate the morphogenetic functions of the J protein and
      possible mechanisms by which it may bind DNA, a genetic analysis was conducted.
      Lysine --> leucine and arginine --> leucine substitutions were generated within
      the basic amino acid clusters. At least three substitutions were required to
      eliminate viability in vivo. Lethal mutants with three or four substitutions
      exhibit dominant lethal phenotypes, indicating that the mutant proteins retain
      enough function to interfere with productive assembly. In cells infected with a
      dominant lethal mutant, noninfectious packaged particles were produced.
      Infectivity can be restored by second-site suppressors in the viral coat protein
      which disrupt polar interactions atop the threefold axis of symmetry in the
      capsid. The viability of strains containing compensating frameshift mutations
      within the proline-rich region suggests that only the proline residues in this
      segment are critical for efficient function.

PMID- 9018138
TI  - DNA replication of wheat dwarf geminivirus vectors: effects of origin structure
      and size.
AB  - Wheat dwarf virus (WDV) is a representative member of subgroup I of the
      Geminiviridae, a unique plant DNA virus family. Since geminivirus DNA replication
      occurs in the host cell nucleus exclusively via double-stranded DNA
      intermediates, a considerable interest has arisen to use them as expression
      vectors. We have used particle bombardment to introduce WDV vectors into cultured
      wheat cells and to analyze the fate of input DNA and the accumulation of newly
      replicated DNA. Under our conditions, we have found that input DNA, which can be
      detected immediately after DNA delivery, is rapidly degraded. Newly replicated
      viral DNA appears approximately 1 day after DNA delivery and reaches a maximum at
      Days 2-4. Afterward, the total amount of viral DNA is maintained for several
      days. We have observed a progressive decrease in the relative amount of
      supercoiled DNA and, concomitantly, an increase in plasmid forms migrating as
      open circular and nicked DNA. GUS expression from the virion-sense WDV promoter
      is also maximal 2-3 days after DNA delivery and then it declines to negligible
      levels 8 days afterward. These results support the conclusion that, under these
      conditions, reporter gene expression depends on the accumulation of newly
      replicated, supercoiled plasmid DNA and not on input plasmid DNA. We have also
      analyzed the effects of WDV origin structure and plasmid size on the accumulation
      of newly replicated plasmid DNA. Our results lead us to conclude that the
      replication efficiency of WDV-derived plasmids depends largely on plasmid size.
      Interestingly, sequences downstream of the initiation site, which in WDV confer
      an intrinsic curvature to the large intergenic region, seem to have a small
      effect on the efficiency of plasmid accumulation.

PMID- 9018137
TI  - Two amino acid changes at the N-terminus of transmissible gastroenteritis
      coronavirus spike protein result in the loss of enteric tropism.
AB  - To study the molecular basis of TGEV tropism, a collection of recombinants
      between the PUR46-MAD strain of transmissible gastroenteritis coronavirus (TGEV)
      infecting the enteric and respiratory tracts and the PTV strain, which only
      infects the respiratory tract, was generated. The recombinant isolation frequency
      was about 10(-9) recombinants per nucleotide and was 3.7-fold higher at the 5'
      end of the S gene than in other areas of the genome. Thirty recombinants were
      plaque purified and characterized phenotypically and genetically. All recombinant
      viruses had a single crossover and had inherited the 5'- and 3'-halves of their
      genome from the enteric and respiratory parents, respectively. Recombinant
      viruses were classified into three groups, named 1 to 3, according to the
      location of the crossover. Group 1 recombinants had the crossover in the S gene,
      while in Groups 2 and 3 the crossovers were located in ORF1b and ORF1a,
      respectively. The tropism of the recombinants was studied. Recombinants of Group
      1 had enteric and respiratory tropism, while Group 2 recombinants infected the
      respiratory, but not the enteric, tract. Viruses of both groups differed by two
      nucleotide changes at positions 214 and 655. Both changes may be in principle
      responsible for the loss of enteric tropism but only the change in nucleotide 655
      was specifically found in the respiratory isolates and most likely this single
      nucleotide change, which leads to a substitution in amino acid 219 of the S
      protein, was responsible for the loss of enteric tropism in the closely related
      PUR46 isolates. The available data indicate that in order to infect enteric tract
      cells with TGEV, two different domains of the S protein, mapping between amino
      acids 522 and 744 and around amino acid 219, respectively, are involved. The
      first domain binds to porcine aminopeptidase N, the cellular receptor for TGEV.
      In the other domain maps a second factor of undefined nature but which may be the
      binding site for a coreceptor essential for the enteric tropism of TGEV.

PMID- 9018139
TI  - Isolation of a gp20-complex and its role in in vitro assembly of both prohead and
      core of bacteriophage T4.
AB  - The product of gene 20 (gp20) in bacteriophage T4 forms the proximal vertex of
      the head. It has been suggested that gp20-rich fractions derived from the
      proheads can initiate core assembly in vitro and that gp20 plays an important
      role in prohead and core assembly. However, the gp20 isolated from proheads or
      overproducing cells harboring gene 20 did not work in vitro, owing to a strong
      tendency to aggregate. Native gp20 was purified from T4-infected Escherichia coli
      hdB3-1 cells, since it was shown that gp20 might not associate with membrane in
      this infection. Isolated gp20 is associated with two other proteins in a gp20
      complex, composed of a connector and a neck joined to six fibers. The gp20
      complex is also produced in T4 infection of E. coli groEL. Moreover, the complex
      can efficiently induce prohead and core assembly and is very stable.

PMID- 9018140
TI  - PCR-directed formation of viral hybrids in vitro.
AB  - When constructing viruses that have desired hybrid phenotypes, anticipated
      difficulties include the nonviability of many, possibly most, of the hybrid
      genomes that can be constructed by incorporation of DNA fragments. Therefore,
      many different hybrid genomes may have to be constructed in order to find one
      that is viable. To perform this combinatorial work in a single experiment, we
      have used bacteriophage T7-infected cell extracts to transfer DNA in vitro. In an
      extract, we have incubated T7 DNA, together with DNA obtained by polymerase chain
      reaction (PCR) amplification of the gene (gene 17) for the tail fiber of the T7
      related bacteriophage, T3. After in vitro packaging of DNA in the extract, hybrid
      progeny bacteriophage were detected by probing with a T3-specific
      oligonucleotide; hybrids are found at a frequency of 0.1%. By determination of
      the nucleotide sequence of the entire gene 17 of 14 independently isolated
      hybrids, both right and left ends of the PCR fragment are found to be truncated
      in all hybrids. For all 14 hybrids, the right end is in the same location; the
      left end is found at 3 different locations. The nonrandom location of the ends is
      explained by selection among different inserts for viability; that is, most of
      the hybrid genomes are nonviable. Some hybrids acquire from T3 the desirable
      phenotype of nonadherence to agarose gels during agarose gel electrophoresis.

PMID- 9018141
TI  - Characterization of host range factor 1 (hrf-1) expression in Lymantria dispar M
      nucleopolyhedrovirus- and recombinant Autographa californica M
      nucleopolyhedrovirus-infected IPLB-Ld652Y cells.
AB  - We previously identified a gene, host range factor 1 (hrf-1), in Lymantria dispar
      M nucleopolyhedrovirus (LdMNPV) which promoted Autographa californica M
      nucleopolyhedrovirus (AcMNPV) replication in a nonpermissive cell line IPLB
      Ld652Y (Ld652Y). A recombinant AcMNPV, vAcLdPS, that bore hrf-1 controlled by two
      synthetic baculovirus late promoters and that replicated in Ld652Y cells was
      constructed. In this study, we constructed a new recombinant AcMNPV, vAcLdPD,
      bearing only hrf-1 controlled by its own promoter. vAcLdPD replicated in Ld652Y
      cells in the same manner as vAcLdPS, confirming that hrf-1 alone was sufficient
      to promote AcMNPV replication in Ld652Y cells. hrf-1 was transcribed as a delayed
      early gene in LdMNPV but as an immediate early gene in both recombinant AcMNPVs.
      Primer extension analysis showed that the initiator sequence TCAGT was used as
      the transcription start site in both LdMNPV and recombinant AcMNPVs. Additional
      sequencing revealed several regulatory motifs in the hrf-1 upstream region. hrf-1
      transcripts in LdMNPV- and vAcLdPS-infected Ld652Y cells terminated near the
      polyadenylation signal at the end of hrf-1 ORF while in vAcLdPD, the hrf-1
      transcripts terminated at a downstream polyadenylation signal at the end of ORF
      603. Using Western blot analysis, we detected HRF-1 expression in both
      recombinant AcMNPV-infected Ld652Y cells but not in LdMNPV-infected Ld652Y cells.

PMID- 9018142
TI  - Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide
      analogs.
AB  - The human immunodeficiency virus type 1 (HIV-1) transactivator Tat protein is
      essential for efficient viral gene expression and virus replication. The Tat core
      domain, a stretch of 12 amino acids between the cysteine-rich and the basic
      domain, is conserved in all HIV isolates and required for interaction with a
      number of cellular transcriptional regulatory proteins. Here we demonstrate that
      soluble peptide analogs of the Tat core domain (amino acid 36-50) are able to
      effectively block LTR transactivation. In transfection experiments, Tat core
      peptide analogs containing amino acid substitutions at position 41 and 44
      inhibited Tat transactivation of an HIV-1 LTR-CAT reporter construct up to 80
      fold. In contrast, inhibition of other promoters such as HTLV-I and CMV was
      approximately 2-fold. Tat peptide analog 36-50 (41/44) inhibited HIV virus
      replication by 85% in latently infected U1 cells induced with Tat. Furthermore,
      U1 cells treated with the Tat peptide 36-50 (41/44) analog showed markedly
      delayed virus transmission when cocultivated with parental U937 cells.
      Interestingly, while both short and long peptide analogs (amino acids 36-50 vs 36
      72) inhibited Tat transactivation in transient assays, the short peptides were
      more effective inhibitors of virus replication in U1 cells. The Tat peptide
      analog did not decrease expression of cellular genes including beta-actin, GAPDH,
      and histone H2B.

PMID- 9018143
TI  - Hepatitis C virus NS5B protein is a membrane-associated phosphoprotein with a
      predominantly perinuclear localization.
AB  - Hepatitis C virus NS5B protein is an RNA-dependent RNA polymerase. To investigate
      the properties and function of this protein, we have expressed the NS5B protein
      in insect and mammalian cells. NS5B was found to be present as fine speckles in
      the cytoplasm, particularly concentrated in the perinuclear region, suggesting
      its association with the nuclear membrane, the endoplasmic reticulum, or the
      Golgi complex. This conclusion was supported by the biochemical demonstration
      that NS5B was associated with the membranes in the cells. Furthermore, it was
      shown that NS5B protein is a phosphoprotein. These properties may be related to
      its function as an RNA polymerase.

PMID- 9018144
TI  - Characterization of a unique OpMNPV-specific early gene not required for viral
      infection in tissue culture.
AB  - opep-2 is an Orgyia pseudotsugata multicapsid nucleopolyhedrovirus (OpMNPV) early
      gene in the ie1-ie2 gene region for which there is no homolog in either the
      archetype virus, Autographa californica MNPV, or Bombyx mori NPV. opep-2 is
      transcribed immediately upon infection as three mRNAs which initiate from a early
      gene motif (TATA-N27-CAGT). The expression of multiple transcripts at very early
      times postinfection has only been previously described for the baculovirus early
      gene ie1, which produces spliced mRNAs. However, distinct from ie1, the multiple
      mRNAs of opep-2 are due to multiple termination sites and not splicing. Western
      blot analysis of steady-state levels of OPEP-2 showed that in OpMNPV-infected
      Ld652Y cells maximum levels are obtained at 8-12 hr postinfection (p.i.) prior to
      DNA replication. By 48 hr p.i. OPEP-2 is shut off and is undetectable. To aid in
      elucidating the function of this OpMNPV-specific gene an opep-2 deletion mutant
      was generated and was compared to wild-type virus to determine if its absence
      affects viral growth in Ld652Y tissue culture cells.

PMID- 9018145
TI  - Initiation of SV40 DNA replication in vitro: analysis of the role played by
      sequences flanking the core origin on initial synthesis events.
AB  - Replication initiation events are suppressed over the SV40 core origin in vitro;
      they are also greatly reduced over sequences flanking the origin which contain
      binding sites for several transcription factors. To address the biochemical basis
      for the gap in initiation events over the flanking sequences, initial synthesis
      events have been characterized on templates lacking these sequences. Herein, it
      is demonstrated that previously functional initiation sites are nearly inactive
      when moved to positions that are proximal to the core origin. Thus, the gap in
      initiation events depends, in part, on the proximity of the initiation sites to
      the SV40 core origin. Additional experiments demonstrate that removal of the
      flanking sequences had little or no effect on DNA unwinding or on the efficiency
      of initiation of DNA synthesis in vitro. These results indicate that, under our
      in vitro conditions, initiation of SV40 DNA synthesis is not enhanced by binding
      of transcription factors to the flanking sequences.

PMID- 9018146
TI  - Sequence close to the N-terminus of L2 protein is displayed on the surface of
      bovine papillomavirus type 1 virions.
AB  - The bovine papillomavirus type 1 (BPV1) L2 protein purified from Escherichia coli
      was used as an antigen to produce monoclonal antibodies (MAbs). A total of 26
      individual clones which recognized the BPV1 L2 protein were obtained. Using
      infectious BPV1 virus particles, 3 of the MAbs were found to interact with BPV1
      virus particles. Binding of the MAbs to BPV1 was confirmed by immunoelectron
      microscopy. A set of 92 13-mer peptides overlapping by 8 amino acids spanning the
      entire BPV1 L2 protein was synthesized on a membrane and used to map the epitopes
      recognized by these antibodies. Seventeen linear epitopes were identified. Our
      results revealed that a sequence toward the N-terminus of the L2 protein (aa 61
      123) is displayed on the virus surface, while the remaining L2 sequences are
      hidden inside the virus capsid. Although the polyclonal antisera raised against
      BPV1 L2 neutralized the BPV1 virus, we failed to detect any neutralizing activity
      for the 3 L2-specific monoclonal antibodies which bound to the BPV1 particles.
      This suggests that extra binding sites may be needed for neutralization. This
      study prompted us to propose a model about how L1 and L2 proteins may interact
      during infectious papillomavirus assembly.

PMID- 9018147
TI  - Epstein-Barr virus (EBV) infection in salivary gland tumors: lytic EBV infection
      in nonmalignant epithelial cells surrounded by EBV-positive T-lymphoma cells.
AB  - To elucidate the association of Epstein-Barr virus (EBV) and salivary gland
      tumors, 114 cases of tumors of major salivary glands were investigated. EBV DNA
      was detected in all 6 cases of undifferentiated carcinoma and all 3 cases of T
      cell lymphoma, but not in other tumor tissues. In situ hybridization studies for
      EBV DNA and EBV-encoded small RNA 1 (EBER1) showed specific localization of the
      EBV sequences to the undifferentiated carcinoma cells and T-lymphoma cells.
      Moreover, intense DNA signals were detected on nonneoplastic epithelial cells of
      T-lymphoma tissues. These epithelial cells were negative for EBER1 and expressed
      BZLF1, BALF2, and gp350/220 proteins associated with virus production. In
      contrast, nonmalignant epithelial cells surrounded by undifferentiated carcinoma
      cells showed no evidence of EBV infection or virus replication. These results
      indicate that there is an unusual association of salivary gland T-cell lymphomas
      with lytic EBV replication of nonmalignant epithelial cells.

PMID- 9018148
TI  - Entry of Semliki forest virus into cells: effects of concanamycin A and nigericin
      on viral membrane fusion and infection.
AB  - Semliki forest virus (SFV) was biosynthetically labeled with pyrene phospholipids
      and used to investigate two alternative routes of entry of SFV into BHK-21 cells:
      (1) receptor-mediated endocytosis followed by fusion of the viral envelope with
      the endosomal membrane and (2) direct fusion of SFV with the plasma membrane
      induced by low pH treatment. The selective inhibitor of the vacuolar proton
      ATPase, concanamycin A, abolished fusion and subsequent infection only when the
      virus utilized the endocytic route to enter cells. The inhibitory effect of this
      macrolide antibiotic was bypassed by low pH treatment of cells. However, the
      ionophore nigericin was inhibitory irrespective of the route used by the virus to
      infect cells, suggesting the necessity of a transmembrane pH gradient for the
      entry process. According to our results, concanamycin A emerges as a suitable
      tool for selectively investigating the involvement of endosomal function in
      animal virus entry.

PMID- 9018149
TI  - Receptor specificity of influenza A viruses correlates with the agglutination of
      erythrocytes from different animal species.
AB  - Despite their uniform ability to bind to oligosaccharide-containing terminal
      sialic acids, influenza A viruses show differences in receptor specificity. To
      test whether agglutination of erythrocytes from different animal species could be
      used to assess the receptor specificity of influenza A viruses, we determined the
      agglutinating activities of a range of virus strains, including those with known
      receptor specificities, using erythrocytes from seven animal species. All equine
      and avian viruses, including those known to recognize N-acetyl and N-glycolyl
      sialic acid linked to galactose by the alpha2,3 linkage (NeuAc alpha2,3Gal and
      NeuGc alpha2,3Gal), agglutinated erythrocytes from all of the animal species
      tested (chickens, ducks, guinea pigs, humans, sheep, horses, and cows). The human
      viruses, including those known to preferentially recognize NeuAc alpha2,6Gal,
      agglutinated all but the horse and cow erythrocytes. Fluorescence-activated cell
      sorting analysis of erythrocytes using linkage-specific lectins [Sambucus nigra
      agglutinin for sialic acid (SA) alpha2,6Gal and Maackia amurensis agglutinin for
      SA alpha2,3Gal] showed that both cow and horse erythrocytes contain a large
      amount of SA alpha2,3Gal-, but virtually no SA2,6Gal-specific lectin-reactive
      oligosaccharides on the cell surface, while human and chicken erythrocytes
      contained both types of oligosaccharides. Considering that the majority (>93%) of
      sialic acid in horse and cow erythrocytes is of the N-glycolyl type, our results
      suggest that viruses able to agglutinate these erythrocytes (i.e., avian and
      equine viruses) recognize NeuGc alpha2,3Gal. These findings also show that
      agglutinating assays with erythrocytes from different animal species would be
      useful in characterizing the receptor specificity of influenza A viruses.

PMID- 9018150
TI  - Experimental confirmation of a hepatitis B virus (HBV) epsilon-like bulge-and
      loop structure in avian HBV RNA encapsidation signals.
AB  - Hepatitis B viruses replicate via reverse transcription of an RNA intermediate.
      This RNA pregenome serves as mRNA and is packaged into capsids and reverse
      transcribed. Both processes require the interaction of the viral reverse
      transcriptase, P protein, with the 5'-proximal epsilon-signals on the pregenome.
      For epsilon of human hepatitis B virus (HBV), the presence of a functionally
      important stem-loop structure with a central bulge, part of which acts as
      template for a short primer of first-strand DNA synthesis, has been
      experimentally confirmed. Based on phylogeny and its functional similarities to
      epsilon, the D epsilon-signal of duck hepatitis B virus (DHBV) had been proposed
      to have a similar structure which does not, however, correspond to the most
      stable computer prediction. We have therefore experimentally determined the
      secondary structures of D epsilon and of the H epsilon-signal of heron hepatitis
      B virus which differs considerably from D epsilon in primary sequence yet
      interacts productively with DHBV P protein. Our data support an HBV epsilon-like
      structure for both D epsilon and H epsilon; in particular the bulge is highly
      conserved, in accord with its special function in replication. However, the
      apical loop in H epsilon is much enlarged suggesting that, by an induced-fit
      mechanism, both RNAs may adopt a new, probably similar conformation in the
      complex with P protein.

PMID- 9018151
TI  - Differences in the UV-crosslinking patterns of the poliovirus 5'-untranslated
      region with cell proteins from poliovirus-susceptible and -resistant tissues.
AB  - The restricted tissue tropism observed in poliovirus infection is not governed
      solely by the expression of the poliovirus receptor (PVR) gene, but might be
      controlled at stages beyond virus entry, such as translation, replication, or
      assembly. Translation of poliovirus RNA by a cap-independent mechanism requires
      interactions of the 5'-untranslated region (5'UTR) with cell proteins. To
      determine whether the patterns of these interacting proteins differ in HeLa cells
      and permissive and nonpermissive tissues, UV-crosslinking assays using the
      poliovirus 5'UTR and tissue extracts from PVR transgenic mice were performed. The
      results indicate a correlation between the presence of a 97-kDa UV-crosslinked
      protein and permissivity to poliovirus infection. Acquired poliovirus
      susceptibility in in vitro-cultured kidney cells also correlates with the
      presence of a 97-kDa crosslinked band. The interaction of the 97-kDa protein from
      HeLa cells and mouse brain with the poliovirus 5'UTR is stable and specific.
      Whether the 97-kDa protein plays a role in poliovirus translation and tissue
      susceptibility remains to be determined.

PMID- 9018152
TI  - Nucleotide sequence of the Barmah Forest virus genome.
AB  - Barmah Forest virus (BFV) is an atypical alphavirus [Dalgarno, L., Short, N. J.,
      Hardy, C. M., Bell, J. R., Strauss, J. H., and Marshall, I. D. (1984). Virology
      133, 416-426] and has been classified as the sole known member of a seventh
      alphavirus serocomplex. The complete nucleotide sequence of BFV genomic RNA is
      11,488 nucleotides in length excluding the poly(A) tail. Two long open reading
      frames in the RNA encode a nonstructural polyprotein of 2411 amino acids and a
      structural polyprotein of 1239 amino acids, respectively. The BFV envelope
      protein E2 is unique among sequenced alphaviruses in having no N-linked
      glycosylation sites; E1 carries two glycosylation sites. From amino acid sequence
      comparisons with sequenced alphaviruses BFV is most closely related to Ross River
      and Semliki Forest viruses. Sequence homology between BFV and other alphaviruses
      is relatively uniform along the length of the nonstructural and structural
      polyproteins, providing no evidence that BFV has arisen from recombination
      between ancestral alphaviruses in the coding region of the genome. The BFV 3'
      noncoding region of 445 nucleotides has unusual features. There are two unrelated
      sequence blocks of 48 nucleotides (sequence I) and 47 nucleotides (sequence II)
      both of which are repeated once. Sequence I is closely related to a repeat in the
      3' noncoding region of Ross River and Getah viruses; sequence II is unrelated to
      repeat blocks in other sequenced alphaviruses. Thus, recombination between
      ancestral viruses may have played a role in the evolution of the BFV 3' noncoding
      region.

PMID- 9018153
TI  - Interaction of transcription factors RFX1 and MIBP1 with the gamma motif of the
      negative regulatory element of the hepatitis B virus core promoter.
AB  - The negative regulatory element (NRE) of the hepatitis B virus (HBV) core
      promoter contains three subregions which act synergistically to suppress core
      promoter activity. One of these subregions, NRE gamma, is active in both HeLa
      cervical carcinoma cells and Huh7 hepatoma cells and was found to be bound by a
      protein factor present in both cell types. Here we show that the transcription
      factor RFX1 can bind to NRE gamma and transactivate the core promoter through
      this site. Mutations which abrogated the gene-suppressive activity of NRE gamma
      prevented RFX1 from binding to NRE gamma. In addition, RFX1 can bind
      simultaneously, most likely as a heterodimer, with the transcription factor MIBP1
      to NRE gamma. In the absence of a cloned MIBP1 gene for further studies, we
      hypothesize that RFX1 acts with MIBP1 to negatively regulate the core promoter
      activity through the NRE gamma site. The ability of RFX1 to transactivate the
      core promoter raises the possibility that RFX1 may play a dual role in regulating
      HBV gene expression.

PMID- 9018183
TI  - Efficacy of nebulized ipratropium in severely asthmatic children.
AB  - STUDY OBJECTIVE: To determine the effect of adding the nebulized anticholinergic
      drug ipratropium bromide to standard therapy compared with standard therapy alone
      for acute severe asthma (peak expiratory flow rate [PEFR] < 50% of predicted) in
      children presenting to the emergency department. METHODS: Ninety children aged 6
      to 18 years were randomly assigned to two groups in a prospective, double-blind,
      placebo-controlled study performed in the ED of an urban children's hospital. All
      children received nebulized albuterol solution (.15 mg/kg) every 30 minutes, and
      all received oral steroids with the second dose of albuterol. Children in group 1
      received ipratropium bromide (500 micrograms/dose) with the first and third dose
      of albuterol those in group 2 received saline placebo instead of ipratropium.
      Pulmonary functions (PEFR and 1-second forced expiratory volume [FEV1]) and
      physiologic measurements were assessed every 30 minutes up to 120 minutes. By
      chance, the baseline values for percent of predicted PEFR and FEV1 differed
      between the two groups. Therefore a multivariate model accounting for both time
      and baseline effects was used to compare the response between groups. RESULTS: On
      average, and adjusting for baseline measures, children in the ipratropium group
      had a significantly greater improvement in percent of predicted PEFR than did
      children in the placebo group at 60 minutes (P = .02), 90 minutes (P = .002), and
      120 minutes (P < .0001). The improvement in percent predicted FEV1 was
      significantly greater for children in the ipratropium group only at 120 minutes
      (P = .013). Nine children (20%) from the ipratropium group and 14 (31.1%) from
      the control group were admitted (P = .33, chi 2). There were no significant
      adverse effects attributable to the ipratropium, and there was no relation
      between ipratropium use and changes in pulse, respiratory rate, blood pressure,
      or oxygen saturation. CONCLUSION: We detected significant improvement in
      pulmonary function studies over 120 minutes in children with severe asthma who
      were given nebulized ipratropium combined with albuterol and oral steroids,
      compared with children who received the standard therapy. Further study is needed
      to determine whether early use of ipratropium decreases the need for
      hospitalization.

PMID- 9018184
TI  - Intravenous versus oral corticosteroids in the management of acute asthma in
      children.
AB  - STUDY OBJECTIVE: To determine whether oral corticosteroids are significantly
      better at preventing the need for hospital admission than i.v. corticosteroids in
      children with moderate to severe asthma exacerbation. METHODS: We carried out a
      randomized, double-blind, controlled trial of patients in the emergency
      department of a tertiary urban children's hospital. Patients who presented to the
      ED with moderate to severe asthma (defined as forced expiratory volume in 1
      second [FEV1] < 60% predicted for height in patients aged 7 to 18 years and as
      Pulmonary Index Score [PIS] between 6 and 11 for patients aged 18 months through
      6 years). Patients were randomized to receive 2 mg/kg oral methylprednisolone or
      2 mg/kg i.v. methylprednisolone 30 minutes after the initial treatment with
      nebulized albuterol. Each patient was otherwise treated with an identical regimen
      of frequent nebulized albuterol and i.v. theophylline for a total of 4 hours.
      RESULTS: Forty-nine patients were enrolled. Four hours after treatment, both
      groups had similar respiratory rates, oxygen saturation, PISs, and FEV1 values.
      Eleven of 23 patients in the oral group (48%) and 13 of 26 patients in the i.v
      group (50%) were admitted to the hospital (P = .88). The 90% confidence interval
      for the 2% cifference in admission rate to the hospital (favoring oral
      methylprednisolone) ranged from 21% (favoring i.v. methylpredinisolone) to 25%
      (favoring oral methylprednisolone). Patients discharged home demonstrated greater
      improvement from baseline with regard to PIS and FEV1 than patients who were
      admitted. Two patients in each group failed to complete the standard treatment or
      returned to the hospital within 48 hours of ED discharge. CONCLUSION: These data
      suggest that for children with moderate to severe asthma exacerbation, hospital
      admission rates are similar in children given oral methylprednisolone and those
      given i.v. methylprednisolone.

PMID- 9018185
TI  - Effect of a pediatric observation unit on the rate of hospitalization for asthma.
AB  - STUDY OBJECTIVE: To determine the asthma admission rate and the rate of repeat
      visits to the emergency department for asthma within 72 hours before and after
      the introduction of an observation unit (OU). When necessary, admission to the
      ward from the OU is usually made within 12 hours. METHODS: We conducted a before
      and-after study with retrospective data collection in an urban tertiary care
      pediatric ED. Our subjects were patients aged 1 to 18 years who presented to the
      ED with asthma. The pre-OU group comprised patients seen between July 1, 1991,
      and June 30, 1992, before the opening of the OU. The post-OU group consisted of
      children seen between July 1, 1993, and June 30, 1994, after the opening of the
      OU. RESULTS: The pre- and post-OU groups had 1,979 and 2,248 asthma visits,
      respectively. The admission rate decreased from 31% in the pre-OU group to 24% in
      the post-OU group (P < .01). The frequency of inpatient admissions of less than
      24 hours decreased from 17% in the pre-OU group to 10% in the post-OU group (P <
      or = 01). The rate of repeat ED visits within 72 hours was 3% in the pre-OU group
      and 5% in the post-OU group (P = .01). CONCLUSION: The use of an OU in the ED was
      associated with a reduction in the hospitalization rate for children with acute
      asthma exacerbation. However, we also noted an increased rate of repeat visits to
      the ED after the introduction of the OU.

PMID- 9018186
TI  - Lights and siren in pediatric 911 ambulance transports: are they being misused?
AB  - STUDY OBJECTIVE: To evaluate the appropriateness of lights and siren (L&S) in the
      transport of pediatric patients by ambulance/emergency medical vehicle in a
      region with no specific guidelines regarding L&S use. METHODS: We reviewed
      audiotapes of eligible calls made during a 7-month period to a pediatric medical
      control center (PMCC) at a children's hospital emergency department in an urban,
      tertiary care. Level trauma center serving the greater Cincinnati area. We
      obtained the following information: L&S use, time of day, patient age, chief
      complaint, vital signs, mental status, and physical examination findings. Final
      disposition was determined from the corresponding ED charts. We also recorded the
      level of training of the emergency medical services personnel (basic versus
      paramedic) and any voluntary comments made by the EMS personnel concerning
      overall patient stability and their comfort with the situation. Patients were
      categorized as being in stable condition if all vital signs and mental status
      were normal, significant abnormalities were absent on examination, and EMS
      personnel stated they were comfortable with the patient's condition.
      Inappropriate use of L&S was defined as "running hot" (using L&S) with a stable
      patient. RESULTS: We reviewed 622 calls; 504 met inclusion criteria. L&S were
      used in 312 (62%); of these instances, 123 (39.4%) were classified as involving
      inappropriate use of L&S. Basic units were more likely to use L&S inappropriately
      with a patient in stable condition than were paramedic units (P < .015).
      Inappropriate use was not related to patient age or time of day. Patients
      transported with inappropriate L&S were more likely to be discharged home than
      were patients whose transports were marked by appropriate L&S use (74% versus
      41%, P < .001). Patients with cardiovascular and respiratory chief complaints
      were more likely to be transported with appropriate L&S than were those with
      general medical, trauma, or central nervous system chief complaints. CONCLUSION:
      In our preliminary study, inappropriate use of L&S in the transport of pediatric
      patients in stable condition is common Definitive studies are needed to evaluate
      the risks and benefits of using L&S.

PMID- 9018187
TI  - Assessment of breath sounds during ambulance transport.
AB  - STUDY OBJECTIVE: To determine whether the environment of a moving ambulance
      affects the ability of our-of-hospital care providers to auscultate breath
      sounds. METHODS: Out-of-hospital care providers assessed breath sounds with a
      previously described breath-sounds model in a quiet environment (control) and in
      a moving ambulance. The setting was a nonurban emergency medical services system
      and an interhospital transport agency based at a 600-plus-bed tertiary care
      center. The participants were physicians, transport nurses, and advanced life
      support EMS providers routinely involved in the emergency out-of-hospital
      treatment and transportation of the ill and injured. The accuracy with which
      participants identified the presence or absence of breath sounds in the two
      environments was compared with the use of the chi 2 test, with the alpha-value
      set at .05. RESULTS: The accuracy of breath-sounds assessment in the control
      environment was 96% (251 of 260); the sensitivity was 96% and the specificity
      97%. The accuracy of breath-sounds assessment in the experimental environment was
      54% (140 of 260); the sensitivity was .09% and the specificity 98%. Participants
      were significantly less likely to hear breath sounds in the moving ambulance than
      in the quiet room (P < .001). CONCLUSION: Assessment of breath sounds is hampered
      by the environment of a moving ambulance.

PMID- 9018188
TI  - Agricultural and horticultural chemical poisonings: mortality and morbidity in
      the United States.
AB  - STUDY OBJECTIVE: To provide a comprehensive analysis of morbidity and mortality
      from poisoning by agricultural and horticultural chemicals in the United States.
      METHODS: Descriptive analysis of national mortality data, National Hospital
      Discharge Survey data, and American Association of Poison Control Centers
      national data for 1985 through 1990. RESULTS: There were 341 fatalities from
      agricultural and horticultural chemicals over the 6-year period, of which 64%
      were suicides, 28% were unintentional, and 8% were of undetermined intent. There
      were 25,418 hospitalizations; 78% were reported to be unintentional. Both deaths
      and hospitalizations occurred more frequently in males, and rates were higher in
      nonwhites than in whites. There were 338,170 poison exposures reported to poison
      centers for fungicides, herbicides, pesticides/insecticides, and rodenticides.
      Life-threatening manifestations or long-term sequelae occurred in 782 cases, and
      97 deaths were reported. Pesticides and insecticides accounted for 72% of the
      poison center cases and 63% of the fatalities. Although they accounted for only
      8% of poison exposures, herbicide deaths were disproportionately high (25%).
      CONCLUSION: Poisonings with agricultural and horticultural chemicals are an
      important public health problem. Prevention efforts need to incorporate the fact
      that many serious cases, such as paraquat poisonings, are suicidal in nature.

PMID- 9018189
TI  - Costs of poisoning in the United States and savings from poison control centers:
      a benefit-cost analysis.
AB  - Data on incidence, medical spending, and payment sources for poisoning were taken
      from the 1987 National Medical Expenditure Survey, 1991 US Vital Statistics, the
      1992 National Hospital Discharge Survey, and 1992 poison control center
      surveillance data. Benefits, measured as percentage reductions in medical
      spending attributable to use of poison control centers, were calculated from
      analyses of published and unpublished studies of jurisdictions in which services
      became unavailable. Medical spending (payments) for poisoning treatment totaled
      $3 billion in 1992. Spending averaged $925 per case. Poison control center
      services were available for 86% of poisonings As used, they reduced the number of
      patients who were medically treated but not hospitalized for poisoning by an
      estimated 350,000 (24%) and the number of hospitalizations by 40,000 (12%) in
      1992. The average public call to a poison control center for aid prevented $175
      in other medical spending. Poison control centers offer a large return on
      investment. Despite their proven benefits, many poison control centers are
      unstably funded and financially strapped, in part because the federal government
      pays far less than its fair share of center costs.

PMID- 9018190
TI  - Are poison control centers cost-effective?

PMID- 9018191
TI  - Hazardous materials exposure information service: development, analysis, and
      medical implications.
AB  - The Hazardous Materials Exposure Information Service (HMEIS) was established at
      the Washington Poison Center (WPC) to rapidly provide information to medical
      professionals who treat victims of hazardous-materials exposure. Incident
      description and exposure information is collected from on-site hazardous
      materials teams and immediately analyzed by WPC medical toxicologists. Diagnostic
      and treatment recommendations are provided to prehospital personnel and receiving
      physicians. Over the first 22 months of operation, 50 calls were received that
      met HMEIS criteria. Of the 466 individuals exposed, 256 (55%) were transported to
      a medical facility for treatment. When the WPC was contacted before the decision
      to transport a patient to a medical facility, 28 of 185 exposure victims (15%)
      were transported, compared with a transport rate of 81% of exposure victims (66%
      change; 95% confidence interval [CI], 60% to 72%) in all other concurrent
      incidents and a historical transport rate of 63% (25% change; 95% CI, 14% to 36%)
      before the establishment of the HMEIS. These findings, although preliminary and
      subject to potential confounding, suggest that the HMEIS reduces health care
      costs through more efficient use of medical resources.

PMID- 9018192
TI  - Incorrect overdose management advice in the Physicians' Desk Reference.
AB  - STUDY HYPOTHESIS: Physicians may consult references such as Physicians' Desk
      Reference (PDR) for overdose management advice. Although PDR recommendations are
      approved by the US Food and Drug Administration (FDA), we hypothesized that they
      are often outdated and potentially hazardous. METHODS: We surveyed physicians who
      consulted our poison center during a 1-month period with regard to their use of
      the PDR for overdose information and also compared PDR overdose treatment
      recommendations with those of five current major toxicology references. For the
      PDR overdose information review we examined data from the American Association of
      Poison Control Centers to identify pharmaceutical categories with the largest
      number of deaths. We reviewed the four leading drugs with at least 1,000 reported
      exposures in each category and identified 20 PDR-listed brand-name products for
      analysis. We obtained the consensus from five current toxicology references on
      contraindicated treatments, ineffective treatments, and specific recommended
      treatments or antidotes. Finally, we compared the overdose management advice
      provided in the 1994 PDR with the toxicology reference consensus. RESULTS: Forty
      of 80 of physicians surveyed (50%) reported use of the PDR for overdose
      information in the preceding 12 months. Of the 20 PDR entries, 16 (80%) had at
      least one deficiency, and 5 (25%) had two or more deficiencies. Thirteen (65%)
      omitted an indicated specific treatment, three (15%) recommended contraindicated
      treatments, and four (20%) advised ineffective treatments with potential for
      harm. Only four entries (20%) had no deficiencies by our survey criteria.
      CONCLUSION: We found serious discrepancies in overdose treatment advice in the
      PDR compared with a consensus of current toxicology references. Altogether, four
      of five PDR entries were deficient, and almost half advised ineffective or
      frankly contraindicated therapies. Despite FDA approval, the use of PDR overdose
      advice in a serious poisoning case could result in unnecessary morbidity or
      mortality.

PMID- 9018193
TI  - Refractory asthma, Part 1: Epidemiology, pathophysiology, pharmacologic
      interventions.

PMID- 9018194
TI  - Refractory asthma, Part 2: Airway interventions and management.

PMID- 9018195
TI  - Do motorcycle helmets affect riders' vision and hearing? National Highway Traffic
      Safety Administration.

PMID- 9018196
TI  - Intravenous lidocaine as adjunctive therapy in the treatment of decompression
      illness.
AB  - Two cases of severe decompression illness for which IV lidocaine was used as
      adjunctive therapy to recompression and hyperbaric oxygen therapy are described.
      The first patient demonstrated improvement only after lidocaine was added to her
      treatment; the second had essentially complete recovery after only a single
      treatment despite severe symptoms and a significant delay in presentation. These
      cases support the need for a controlled clinical trial of lidocaine as an adjunct
      to hyperbaric therapy in decompress on illness.

PMID- 9018197
TI  - Serotonin syndrome associated with nefazodone and paroxetine.
AB  - A 51-year-old woman was brought to the emergency department unresponsive,
      hyponatremic, and diaphoretic, with muscle rigidity. Her condition improved
      dramatically after supportive treatment and dantrolene. The patient had received
      nefazodone for 6 months, but the drug had been discontinued 2 days before
      admission after a tapering period. One day before admission, paroxetine 20 mg/day
      was started. A repeat challenge with paroxetine 7 days after discontinuation of
      nefazodone did not result in recurrence of the patient's symptoms. We believe
      this to be the first report of serotonin syndrome associated with nefazodone and
      paroxetine.

PMID- 9018198
TI  - Epidemic of accidental carbon monoxide poisonings caused by snow-obstructed
      exhaust systems.
AB  - We report a case series of accidental carbon monoxide poisonings caused by snow
      obstructed automobile exhaust systems. Accumulation of more than 24 inches of
      snow contributed to the poisoning of 25 patients who were subsequently treated
      with hyperbaric oxygen therapy. Two illustrative cases are presented in greater
      detail, illustrating a life-threatening hazard associated with heavy snow
      accumulations.

PMID- 9018199
TI  - Diagnosis of ectopic pregnancy.

PMID- 9018200
TI  - Analgesia in renal colic.

PMID- 9018201
TI  - Analgesia in renal colic.

PMID- 9018202
TI  - Analgesia in renal colic.

PMID- 9018203
TI  - Organophosphate poisoning in pregnancy.

PMID- 9018204
TI  - Psychologic treatment by EMS personnel in disasters.

PMID- 9018205
TI  - Zolpidem and hallucinations.

PMID- 9018206
TI  - EMS and emergency physicians.

PMID- 9018207
TI  - Rhabdomyolysis and suicidal hydrocarbon inhalation.

PMID- 9018208
TI  - Uninsured in an era of managed care.

PMID- 9018209
TI  - Shaping the future.

PMID- 9018210
TI  - Using Medicare claims data to assess provider quality for CABG surgery: does it
      work well enough?
AB  - OBJECTIVES: To assess the relative abilities of clinical and administrative data
      to predict mortality and to assess hospital quality of care for CABG surgery
      patients. DATA SOURCES/STUDY SETTING: 1991-1992 data from New York's Cardiac
      Surgery Reporting System (clinical data) and HCFA's MEDPAR (administrative data).
      STUDY DESIGN/SETTING/SAMPLE: This is an observational study that identifies
      significant risk factors for in-hospital mortality and that risk-adjusts hospital
      mortality rates using these variables. Setting was all 31 hospitals in New York
      State in which CABG surgery was performed in 1991-1992. A total of 13,577
      patients undergoing isolated CABG surgery who could be matched in the two
      databases made up the sample. MAIN OUTCOME MEASURES: Hospital risk-adjusted
      mortality rates, identification of "outlier" hospitals, and discrimination and
      calibration of statistical models were the main outcome measures. PRINCIPAL
      FINDINGS: Part of the discriminatory power of administrative statistical models
      resulted from the miscoding of postoperative complications as comorbidities.
      Removal of these complications led to deterioration in the model's C index (from
      C = .78 to C = .71 and C = .73). Also, provider performance assessments changed
      considerably when complications of care were distinguished from comorbidities.
      The addition of a couple of clinical data elements considerably improved the fit
      of administrative models. Further, a clinical model based on Medicare CABG
      patients yielded only three outliers, whereas eight were identified using a
      clinical model for all CABG patients. CONCLUSIONS: If administrative databases
      are used in outcomes research, (1) efforts to distinguish complications of care
      from comorbidities should be undertaken, (2) much more accurate assessments may
      be obtained by appending a limited number of clinical data elements to
      administrative data before assessing outcomes, and (3) Medicare data may be
      misleading because they do not reflect outcomes for all patients.

PMID- 9018211
TI  - Effects of market position and competition on rural hospital closures.
AB  - OBJECTIVE: To examine the dynamic effects of competition and hospital market
      position on rural hospital closures. DATA SOURCE/STUDY SETTING: Analysis of all
      rural community hospitals operating between 1984 and 1991, with the exception of
      sole-provider hospitals. Data for the study are obtained from four sources: the
      AHA Annual Surveys of Hospitals, the HCFA Cost Reports, the Area Resource File,
      and a hospital address file constructed by Geographic Inc. DATA COLLECTION AND
      ANALYSIS: Variables are merged to construct pooled, time-series observations for
      study hospitals. Hospital closure is specified as a function of hospital market
      position, market level competition, and control variables. Discrete-time logistic
      regressions are used to test hypotheses. PRINCIPAL FINDINGS: Rural hospitals
      operating in markets with higher density had higher risk of closure. Rural
      hospitals that differentiated from others in the market on the basis of
      geographic distance, basic services, and high-tech services had lower risks of
      closure. Effects of market density on closure disappeared when market position
      was included in the model, indicating that differentiation in markets should be
      taken into account when evaluating the effects of competition on rural hospital
      closure. CONCLUSIONS: Our findings suggest that rural hospitals can reduce
      competitive pressures through differentiation and that accurate measures of
      competition in geographically defined market areas are critical for understanding
      competitive dynamics among rural hospitals.

PMID- 9018212
TI  - Hospital mergers and market overlap.
AB  - OBJECTIVE: To address two questions: What are the characteristics of hospitals
      that affect the likelihood of their being involved in a merger? What
      characteristics of particular pairs of hospitals affect the likelihood of the
      pair engaging in a merger? DATA SOURCES/STUDY SETTING: Hospitals in the 12 county
      region surrounding the San Francisco Bay during the period 1983 to 1992 were the
      focus of the study. Data were drawn from secondary sources, including the
      Lexis/Nexis database, the American Hospital Association, and the Office of
      Statewide Health Planning and Development of the State of California. STUDY
      DESIGN: Seventeen hospital mergers during the study period were identified. A
      random sample of pairs of hospitals that did not merge was drawn to establish a
      statistically efficient control set. Models constructed from hypotheses regarding
      hospital and market characteristics believed to be related to merger likelihood
      were tested using logistic regression analysis. DATA COLLECTION: See Data
      Sources/Study Setting. PRINCIPAL FINDINGS: The analysis shows that the likelihood
      of a merger between a particular pair of hospitals is positively related to the
      degree of market overlap that exists between them. Furthermore, market overlap
      and performance difference interact in their effect on merger likelihood. In an
      analysis of individual hospitals, conditions of rivalry, hospital market share,
      and hospital size were not found to influence the likelihood that a hospital will
      engage in a merger. CONCLUSIONS: Mergers between hospitals are not driven
      directly by considerations of market power or efficiency as much as by the
      existence of specific merger opportunities in the hospitals' local markets.
      Market overlap is a condition that enables a merger to occur, but other factors,
      such as the relative performance levels of the hospitals in question and their
      ownership and teaching status, also play a role in influencing the likelihood
      that a merger will in fact take place.

PMID- 9018213
TI  - Forecasting the need for physicians in the United States: the Health Resources
      and Services Administration's physician requirements model.
AB  - OBJECTIVE: The Health Resources and Services Administration's Bureau of Health
      Professions developed a demographic utilization-based model of physician
      specialty requirements to explore the consequences of a broad range of scenarios
      pertaining to the nation's health care delivery system on need for physicians.
      DATA SOURCE/STUDY SETTING: The model uses selected data primarily from the
      National Center for Health Statistics, the American Medical Association, and the
      U.S. Bureau of Census. Forecasts are national estimates. STUDY DESIGN: Current
      (1989) utilization rates for ambulatory and inpatient medical specialty services
      were obtained for the population according to age, gender, race/ethnicity, and
      insurance status. These rates are used to estimate specialty-specific total
      service utilization expressed in patient care minutes for future populations and
      converted to physician requirements by applying per-physician productivity
      estimates. DATA COLLECTION/EXTRACTION METHODS: Secondary data were analyzed and
      put into matrixes for use in the mainframe computer-based model. Several missing
      data points, e.g., for HMO-enrolled populations, were extrapolated from available
      data by the project's contractor. PRINCIPAL FINDINGS: The authors contend that
      the Bureau's demographic utilization model represents improvements over other
      data-driven methodologies that rely on staffing ratios and similar supply
      determined bases for estimating requirements. The model's distinct utility rests
      in offering national-level physician specialty requirements forecasts.

PMID- 9018214
TI  - Where do elderly veterans obtain care for acute myocardial infarction: Department
      of Veterans Affairs or Medicare?
AB  - OBJECTIVE: To examine Department of Veterans Affairs (VA) and Medicare
      hospitalizations for elderly veterans with acute myocardial infarction (AMI),
      their use of cardiac procedures in both systems, and patient mortality. DATA
      SOURCES: Merging of inpatient discharge abstracts obtained from VA Patient
      Treatment Files (PTF) and Medicare MedPAR Part A files. STUDY DESIGN: A
      retrospective cohort study of male veterans 65 years or older who were prior
      users of the VA medical system (veteran-users) and who were initially admitted to
      a VA or Medicare hospital with a primary diagnosis of AMI at some time from
      January 1, 1988 through December 31, 1990 (N = 25,312). We examined the use of
      cardiac catheterization, coronary bypass surgery, and percutaneous transluminal
      coronary angioplasty in the 90 days after initial admission for AMI in both VA
      and Medicare systems, and survival at 30 days, 90 days, and one year. Other key
      measures included patient age, race, marital status, comorbidities, cardiac
      complications, prior utilization, and the availability of cardiac technology at
      the admitting hospital. PRINCIPAL FINDINGS: More than half of veteran-users (54
      percent) were initially hospitalized in a Medicare hospital when they suffered an
      AMI. These Medicare index patients were more likely to receive cardiac
      catheterization (OR 1.24, 95% C.I. 1.17-1.32), coronary bypass surgery (OR 2.01,
      95% C.I. 1.83-2.20), and percutaneous transluminal coronary angioplasty (OR 2.56,
      95% C.I. 2.30-2.85) than VA index patients. Small proportions of patients crossed
      over between systems of care for catheterization procedures (VA to Medicare =
      3.3%, and Medicare to VA = 5.1%). Many VA index patients crossed over to Medicare
      hospitals to obtain bypass surgery (27.6 percent) or coronary angioplasty (12.1
      percent). Mortality was not significantly different between veteran-users who
      were initially admitted to VA versus Medicare hospitals. CONCLUSIONS: Dual-system
      utilization highlights the need to look at both systems of care when evaluating
      access, costs, and quality either in VA or in Medicare systems. Policy changes
      that affect access to and utilization of one system may lead to unpredictable
      results in the other.

PMID- 9018215
TI  - Does case mix matter for substance abuse treatment? A comparison of observed and
      case mix-adjusted readmission rates for inpatient substance abuse treatment in
      the Department of Veterans Affairs.
AB  - OBJECTIVE: To develop a case mix model for inpatient substance abuse treatment to
      assess the effect of case mix on readmission across Veterans Affairs Medical
      Centers (VAMCs). DATA SOURCES/STUDY SETTING: The computerized patient records
      from the 116 VAMCs with inpatient substance abuse treatment programs between 1987
      and 1992. STUDY DESIGN: Logistic regression was used on patient data to model the
      effect of demographic, psychiatric, medical, and substance abuse factors on
      readmission to VAMCs for substance abuse treatment within six months of
      discharge. The model predictions were aggregated for each VAMC to produce an
      expected number of readmissions. The observed number of readmissions for each
      VAMC was divided by its expected number to create a measure of facility
      performance. Confidence intervals and rankings were used to examine how case mix
      adjustment changed relative performance among VAMCs. DATA COLLECTION/EXTRACTION
      METHODS: Ward where care was provided and ICD-9-CM diagnosis codes were used to
      identify patients receiving treatment for substance abuse (N = 313,886).
      PRINCIPAL FINDINGS: The case mix model explains 36 percent of the observed
      facility level variation in readmission. Over half of the VAMCs had numbers of
      readmissions that were significantly different than expected. There were also
      noticeable differences between the rankings based on actual and case mix-adjusted
      readmissions. CONCLUSIONS: Secondary data can be used to build a reasonably
      stable case mix model for substance abuse treatment that will identify meaningful
      variation across facilities. Further, case mix has a large effect on facility
      level readmission rates for substance abuse treatment. Uncontrolled facility
      comparisons can be misleading. Case mix models are potentially useful for quality
      assurance efforts.

PMID- 9018216
TI  - The relationship between price of services, quality of care, and patient time
      costs for general dental practice.
AB  - OBJECTIVE: To examine the relationships between price of services, quality of
      care, and patient time costs in private practices of general dentists. DATA
      SOURCE/STUDY SETTING: In October 1992, a 3.7 percent sample of eligible general
      dentists in part-time or full-time private practice in 1991 was randomly drawn
      from a sampling frame tailored from data gathered by the 1991-1992 American
      Dental Association Distribution of Dentists census of all United States dentists.
      DATA COLLECTION: A mail survey was used to collect data on dentist demographic
      characteristics, dental practice characteristics practice finances, and
      insurance. The survey was completed and returned by 3,048 general dentists (77
      percent response rate). Local area population characteristics were obtained from
      secondary sources. STUDY DESIGN: Two-stage least squares regression was used to
      evaluate the structural relationships between price of services, quality of care,
      and time costs to patients. Structural equations were estimated for four
      different quality of care measures and two time costs. PRINCIPAL FINDINGS: Price
      of services and quality of care were significantly related to each other. Higher
      quality of care was associated with higher price of services and, reciprocally,
      higher price of services was associated with higher quality of care. Shorter
      waits for a new patient appointment were associated with higher prices. Higher
      price of services, lower quality of care, and longer waits for a new patient
      appointment were related to shorter in-office waiting time. CONCLUSIONS: The
      implication of these findings is that if price of services is constrained, then
      the quality of care provided by the dentist may also be reduced.

PMID- 9018217
TI  - Hepatitis C virus among health care workers.
AB  - The purpose of our study was to describe the results of a seroprevalence survey
      for HCV antibody among health care workers at our center. 961 specimens were
      consecutively obtained under code and screened for anti-HCV by the second
      generation immunoblot assay (RIBA 2) and hepatitis B core antibody by CORAB test.
      After serum samples were tested, we reviewed demographic data and categorized
      four groups: intravenous drug abusers (IVDAs), blood recipients, health care
      workers and apparently healthy subjects. 51/97 (52.6%) IVDAs, 8/77 (10.4%)
      transfusion recipients, 12/472 (2.5%) health care workers and 8/285 (2.8%)
      apparently healthy subjects were anti-HCV positive. Furthermore dividing health
      care personnel by type of profession we found that surgeons have a higher
      seroprevalence (4.3%) compared to other professions. Therefore severe preventive
      standards are required for health care workers.

PMID- 9018219
TI  - Scientific "experts" and the law.

PMID- 9018218
TI  - Relevance of postprandial glycosuria in survey for diabetes mellitus.
AB  - Since the oral glucose tolerance test is not applicable in large surveys for
      diabetes mellitus, economic tests or clinical criteria are required to select
      subjects needing a complete glycometabolic assessment. This study evaluated, in a
      selected high risk population (110 subjects; 71 males; median age: 53 years,
      range 30-70), the utility of glycosuria after a meal rich in carbohydrates in the
      detecting of diabetes, compared to other tests for glycosuria (fasting
      glycosuria, glycosuria after a glucose load) and clinical criteria (diabetic
      family history, overweight and their combination). For each test and,
      retrospectively, for clinical criteria, sensitivity, sensibility, predictive
      value positive (PVP) and predictive value negative (PVN) were calculated.
      Postprandial glycosuria resulted to be an effective approach (sensitivity: 100%;
      specificity: 44%; PVP: 23%, PVN: 100%) in people over 50 years old, in which both
      clinical criteria (sensitivity: 22-78%; PVN: 81-90%) and fasting glycosuria
      (sensitivity 11%; PVN: 86%) proved defective. In younger subjects both the
      presence of fasting glycosuria (sensitivity: 100%; specificity: 96%; PVP: 33%;
      PVN: 100%) and of relevant diabetic family history (sensitivity: 100%;
      specificity: 85%; PVN: 100%) proved more adequate as screening procedures.

PMID- 9018220
TI  - Contraceptives and HIV transmission.

PMID- 9018221
TI  - Mitochondrial mutations and male infertility.

PMID- 9018222
TI  - One too many tricks.

PMID- 9018223
TI  - The best cytokine for the job.

PMID- 9018224
TI  - Clinical investigators as critical determinants in pharmaceutical innovation.

PMID- 9018225
TI  - Terms of attachment: SPARC and tumorigenesis.

PMID- 9018226
TI  - Preterm birth, cerebral palsy and magnesium.

PMID- 9018227
TI  - Unconventional T-cell activation by IL-15 in rheumatoid arthritis.

PMID- 9018228
TI  - Trinucleotide repeats and hereditary ataxias.

PMID- 9018229
TI  - Breast cancer and osteolytic metastases: can bisphosphonates help?

PMID- 9018230
TI  - Cancer prognostics: past, present and p27.

PMID- 9018231
TI  - Platelet stimulating agents--off the launching pad.

PMID- 9018232
TI  - A naturally unbalanced combat [new; comment].

PMID- 9018233
TI  - Angiogenesis in ischemic heart disease.

PMID- 9018234
TI  - Antitumor effect of locally produced CD95 ligand.
AB  - Activation of the cell-surface antigen CD95 induces apoptosis of CD95-bearing
      tumor cells. In this study, we investigated the antitumor effect of locally
      produced CD95 ligand (CD95L) on CD95-negative tumor cells in vivo. Introduction
      of CD95L cDNA into murine tumor cells did not affect growth in vitro but caused
      rejection in vivo. Neutrophils were primarily responsible for this rejection. A
      CD8 T cell-mediated protective immunity against subsequent challenge with
      parental tumor cells was also elicited. These results provide evidence for the
      potential utility of CD95L in tumor eradication and also reveal a proinflammatory
      function of CD95L.

PMID- 9018235
TI  - Suppression of SPARC expression by antisense RNA abrogates the tumorigenicity of
      human melanoma cells.
AB  - Acquisition of invasive/metastatic potential is a key event in tumor progression.
      Cell surface glycoproteins and their respective matrix ligands have been
      implicated in this process. Recent evidence reveals that the secreted
      glycoprotein SPARC (secreted protein, acidic and rich in cysteine) is highly
      expressed in different malignant tissues. The present study reports that the
      suppression of SPARC expression by human melanoma cells using a SPARC antisense
      expression vector results in a significant decrease in the in vitro adhesive and
      invasive capacities of tumor cells, completely abolishing their in vivo
      tumorigenicity. This is the first evidence that SPARC plays a key role in human
      melanoma invasive-metastatic phenotype development.

PMID- 9018236
TI  - Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution
      measurements reveal a lack of correlation.
AB  - The partial pressure of oxygen (pO2) and pH play critical roles in tumor biology
      and therapy. We report here the first combined, high-resolution (< or = 10
      microns) measurements of interstitial pH and pO2 profiles between adjacent
      vessels in a human tumor xenograft, using fluorescence ratio imaging and
      phosphorescence quenching microscopy. We found (1) heterogeneity in shapes of pH
      and pO2 profiles; (2) a discordant relation between local pH profiles and
      corresponding pO2 profiles, yet a strong correlation between mean pH and pO2
      profiles; (3) no correlation between perivascular pH/pO2 and nearest vessel blood
      flow; and (4) well-perfused tumor vessels that were hypoxic and, consequently,
      large hypoxic areas in the surrounding interstitium. Such multiparameter
      measurements of the in vivo microenvironment provide unique insights into
      biological processes in tumors and their response to treatment.

PMID- 9018237
TI  - Murine psoriasis-like disorder induced by naive CD4+ T cells.
AB  - Psoriasis is a complex disorder involving alterations of many cell types.
      Although evidence suggests a T-cell pathogenesis for psoriasis, a primary role of
      T cells has not been directly demonstrated. Here, we show that reconstitution of
      scid/scid mice with minor histocompatibility mismatched naive CD4+ T lymphocytes
      resulted in skin alterations that strikingly resembled human psoriasis
      clinically, histopathologically and in cytokine expression. This skin disorder
      was diminished when memory T cells were coinjected. Thus, a subset of
      dysregulated CD4+ T cells can cause tissue alterations seen in psoriasis without
      the presence of CD8+ cells or a primary epithelial abnormality.

PMID- 9018238
TI  - Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor
      alpha production in rheumatoid arthritis.
AB  - Tumor necrosis factor-alpha occupies a central role in rheumatoid arthritis (RA)
      pathogenesis. We now report that interleukin-15 (IL-15) can induce TNF-alpha
      production in RA through activation of synovial T cells. Peripheral blood (PB) T
      cells activated by IL-15 induced significant TNF-alpha production by macrophages
      via a cell-contact-dependent mechanism. Freshly isolated RA synovial T cells
      possessed similar capability, and in vitro, IL-15 was necessary to maintain this
      activity. IL-15 also induced direct TNF-alpha production by synovial T cells. In
      contrast, IL-2 induced significantly lower TNF-alpha production in either cell
      contact-dependent or direct culture, and IL-8 and MIP-1 alpha were ineffective.
      Antibodies against CD69, LFA-1 or ICAM-1 significantly inhibited the ability of T
      cells to activate macrophages by cell contact.

PMID- 9018239
TI  - Accommodation of vascularized xenografts: expression of "protective genes" by
      donor endothelial cells in a host Th2 cytokine environment.
AB  - Organ xenografts under certain circumstances survive in the presence of anti
      graft antibodies and complement, a situation referred to as "accommodation." We
      find that the endothelial cells (ECs) in hamster hearts that accommodate
      themselves in rats express genes, such as A20 and bcl-2, that in vitro protect
      ECs from apoptosis and prevent upregulation in those cells of proinflammatory
      genes such as cytokines, procoagulant and adhesion molecules. Hearts that are
      rejected do not express these genes. In addition, vessels of rejected hearts show
      florid transplant arteriosclerosis whereas those of accommodated hearts do not.
      Accommodated xenografts have an ongoing T helper cell type 2 (Th2) cytokine
      immune response, whereas the rejected grafts have a Th1 response. We propose a
      model for factors that contribute to the survival of xenografts and the avoidance
      of transplant arteriosclerosis.

PMID- 9018240
TI  - Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs)
      during primary infection demonstrated by rapid selection of CTL escape virus.
AB  - The HIV-1-specific cytotoxic T lymphocyte (CTL) response is temporally associated
      with the decline in viremia during primary HIV-1 infection, but definitive
      evidence that it is of importance in virus containment has been lacking. Here we
      show that in a patient whose early CTL response was focused on a highly
      immunodominant epitope in gp 160, there was rapid elimination of the transmitted
      virus strain and selection for a virus population bearing amino acid changes at a
      single residue within this epitope, which conferred escape from recognition by
      epitope-specific CTL. The magnitude (> 100-fold), kinetics (30-72 days from onset
      of symptoms) and genetic pathways of virus escape from CTL pressure were
      comparable to virus escape from antiretroviral therapy, indicating the biological
      significance of the CTL response in vivo. One aim of HIV-1 vaccines should thus
      be to elicit strong CTL responses against multiple codominant viral epitopes.

PMID- 9018241
TI  - Late escape from an immunodominant cytotoxic T-lymphocyte response associated
      with progression to AIDS.
AB  - The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV
      infection remains controversial. Despite strong CTL responses being generated
      during the asymptomatic phase, the virus persists and AIDS ultimately develops.
      It has been argued that the virus is so variable, and the virus turnover so great
      that escape from CTL recognition would occur continually, but so far there is
      limited evidence for CTL escape. The opposing argument is that evidence for CTL
      escape is present but hard to find because multiple anti-HIV immune responses are
      acting simultaneously during the asymptomatic phase of infection. We describe six
      donors who make a strong CTL response to an immunodominant HLA-B27-restricted
      epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the
      same mutation was observed, but only after 9-12 years of epitope stability. CTL
      escape may play an important role in the pathogenesis of HIV infection.

PMID- 9018242
TI  - A new approach to investigating the relationship between productive infection and
      cytopathicity in vivo.
AB  - We describe a novel experimental approach to analyzing virus-host relationships
      and potential mechanisms of cytopathicity in vivo in simian immunodeficiency
      virus (SIV) infections. Progressive destruction of lymphoid tissue in the course
      of infection by SIV or human immunodeficiency virus (HIV) accompanies the loss of
      CD4+ T lymphocytes and sets the stage for AIDS. Because one of the important
      early events in this pathological process is lysis of follicular dendritic cells
      (FDCs), we investigated the controversial role of productive SIV infection in the
      destruction of FDCs. To differentiate productive infections from the known
      association of virus with FDCs as immune complexes trapped on cell surfaces, we
      used detection of spliced viral mRNAs in cells as evidence of productive
      infection. We found that spliced and unspliced viral RNAs could be detected by in
      situ hybridization (ISH) with specific antisense oligonucleotide probes in
      lymphocytes and macrophages with sensitivities of fewer than ten copies of
      spliced viral RNA per cell. We detected only unspliced RNA in germinal centers
      where FDCs reside. Thus, no productive infection of these cells can be detected
      in vivo by this assay, and their destruction likely occurs by indirect mechanisms
      that have yet to be determined.

PMID- 9018243
TI  - Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in
      combination, correlate with survival in young breast cancer patients.
AB  - Mutations in certain genes that regulate the cell cycle, such as p16 and p53, are
      frequently found in human cancers. However, tumor-specific mutations are uncommon
      in genes encoding cyclin E and the CDK inhibitor p27Kip1, two cell-cycle
      regulators that are also thought to contribute to tumor progression. It is now
      known that levels of both cyclin E and p27 can be controlled by
      posttranscriptional mechanisms, indicating that expression of these proteins can
      be altered by means other than simply mutation of their respective genes. Thus,
      changes in p27 and cyclin E protein levels in tumors might be more common than
      previously anticipated and may be indicators of tumor behavior.

PMID- 9018244
TI  - Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic
      implications in primary breast cancer.
AB  - Breast cancer is the second leading cause of cancer death in North American
      women. There is considerable need for reliable prognostic markers to assist
      clinicians in making management decisions. Although a variety of factors have
      been tested, only tumor stage, grade, size, hormone receptor status, and S-phase
      fraction are used on a routine basis. The cell cycle is governed by a family of
      cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by
      phosphorylation. p27Kip1, a cyclin-dependent kinase inhibitor, regulates
      progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27Kip1
      protein levels and/or activity are upregulated by growth inhibitory cytokines
      including transforming growth factor-beta (TGF-beta) and, thus, provide an
      important link between extracellular regulators and the cell cycle. Loss of
      p27Kip1, a negative cell-cycle regulator, may contribute to oncogenesis and tumor
      progression. However, p27Kip1 mutations in human tumors are extremely rare. We
      have demonstrated by immunohistochemistry that p27Kip1 protein levels are reduced
      in primary breast cancers and that this is associated with tumor progression in
      both in situ and invasive lesions. This was confirmed by western analysis,
      reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to
      be regulated posttranscriptionally by in situ hybridization. Furthermore, on
      multivariate analysis, low p27Kip1 is a predictor of reduced disease-free
      survival. This simple and reliable immunohistochemical assay may become a routine
      part of breast cancer evaluation and may influence patient management.

PMID- 9018245
TI  - Increased proteasome-dependent degradation of the cyclin-dependent kinase
      inhibitor p27 in aggressive colorectal carcinomas.
AB  - The cell-cycle inhibitor p27 is a potential tumor suppressor, but its gene has
      never been found inactivated in human tumors. Because cell-cycle regulation of
      p27 cellular abundance occurs at the post-transcriptional level, we analyzed p27
      protein expression and degradation in human colorectal carcinomas. Proteasome
      mediated degradation activity of p27 was compared with its protein levels in a
      subset of tumor samples. We found that carcinomas with low or absent p27 protein
      displayed enhanced proteolytic activity specific for p27, suggesting that low p27
      expression can result from increased proteasome-mediated degradation rather than
      altered gene expression. Patients whose tumors expressed p27 had a median
      survival of 151 months, whereas patients who lacked p27 (10%) had a median
      survival of 69 months. By multivariate analysis, p27 was found to be an
      independent prognostic marker. Lack of p27 was associated with poor prognosis
      (2.9 risk ratio for death; P = 0.003). The absence of p27 protein expression is
      thus a powerful negative prognostic marker in colorectal carcinomas, particularly
      in stage II tumors, and thereby may help in the selection of patients who will
      benefit from adjuvant therapy. These data suggest that aggressive tumors may
      result from the selection of a clone or clones that lack p27 due to increased
      proteasome-mediated degradation.

PMID- 9018246
TI  - Visualization of silicone gel in human breast tissue using new infrared imaging
      spectroscopy.
AB  - Between 1 and 2 million women in the United States have silicone breast implants.
      Complications include capsular contracture and calcification and possibly
      connective tissue diseases such as scleroderma and rheumatoid arthritis, a
      subject of some controversy. In order to accurately assess the role of silicone
      in any histopathologic change, it is necessary to confirm its presence and to
      identify other foreign materials in the capsular tissue. Although light
      microscopy is used to visualize regions of tissue containing foreign inclusions,
      their chemical identity can only be determined using analytical techniques such
      as infrared or Raman microscopy. However, these conventional microprobe
      techniques record spectra only at single points and require an a priori knowledge
      of the locations of the inclusion to be probed. To significantly extend the
      capabilities of both infrared spectroscopy and optical microscopy, we have
      developed a new infrared imaging system that completely integrates these two
      methods. In this manuscript we highlight the ability of the technique to screen
      rapidly and to determine accurately the presence, size and chemical composition
      of silicone gel inclusions in human breast tissue.

PMID- 9018247
TI  - Relatively low plasma leptin concentrations precede weight gain in Pima Indians.
AB  - Leptin, the product of the ob gene, is a hormone, produced by adipose cells, that
      inhibits food intake and increases energy expenditure in rodents. In humans,
      plasma leptin concentrations correlate closely with the size of the adipose
      tissue depot; however, there is considerable variation in plasma leptin
      concentrations at any given degree of fatness. To investigate whether individuals
      prone to weight gain are hypoleptinemic, we measured fasting plasma leptin
      concentrations in two groups of weight-matched nondiabetic Pima Indians followed
      for approximately 3 years, 19 of whom subsequently gained weight and 17 of whom
      maintained their weight. After we adjusted for initial percent body fat, mean
      plasma leptin concentration was lower in those who gained weight than in those
      whose weight was stable. These data indicate that relatively low plasma leptin
      concentrations may play a role in the development of obesity in Pima Indians, a
      population prone to obesity.

PMID- 9018248
TI  - In vivo confocal neuroimaging (ICON) of CNS neurons.

PMID- 9018249
TI  - Thou shall not kill.

PMID- 9018250
TI  - Pediatric sinusitis: a literature review with emphasis on the role of allergy.
AB  - Evaluation and treatment of pediatric sinusitis is a challenging area that has
      been subject to many different opinions and options during the past decade.
      Sinusitis is among the most commonly encountered diseases of childhood and has
      been the major area of interest for many otolaryngologists, allergists, and
      pediatricians. We have searched the medical literature to review the many aspects
      of the problem and the opinions of various authors. The increasing importance of
      allergic diseases and their relationship to sinus disease have been evaluated
      through a review of relevant literature. The poorly understood variations of the
      presentation of sinusitis and its signs and symptoms in the pediatric age group
      have been reviewed. Recommendations concerning the method, duration, and timing
      of the therapeutic intervention or interventions are summarized. The natural
      course of pediatric sinusitis in association with related respiratory tract
      diseases is discussed. Allergies and viral upper respiratory infections are among
      the most common predisposing factors of sinus disease. Every child with sinusitis
      is a candidate for an allergy evaluation.

PMID- 9018251
TI  - Contemporary management of deep neck space infections.
AB  - Deep neck infections continue to be seen despite the wide use of antibiotics.
      These infections follow along fascial planes to create deep neck space abscesses.
      The clinical presentation often points to the space involved. Understanding the
      regional anatomy gives the surgeon the ability to treat these grave infections.
      The records of 24 patients with a diagnosis of deep neck space abscess admitted
      to Hermann Hospital between 1988 and 1993 were reviewed. Fifty percent of the
      patients had received antibiotics for an infection of the ear, nose, or throat
      before the development of a neck space abscess. Ten patients had parapharyngeal
      abscesses, seven had retropharyngeal abscesses, six had submandibular space
      abscesses, and one had parotid space abscess. Thirty-five organisms were isolated
      in 18 cases (1.9 isolates per patient). The most common organism cultured was
      Streptococcus (13 of 18), followed by Staphylococcus (6 of 18), Bacteroides (5 of
      18), Micrococcus (2 of 18), and Neisseria (2 of 18). One case each of Candida,
      Enterobacter, Enterococcus, Peptostreptococcus, Proteus, Proprionobacter, and
      Pseudomonas was cultured. Six patients had no growth on culture but did have
      organisms found on Gram's stain. The operative techniques and antibiotics used
      are discussed. The main complications of jugular vein thrombosis, carotid artery
      rupture, and mediastinitis are described, as well as an unusual case of
      meningitis from a large retropharyngeal-parapharyngeal abscess.

PMID- 9018252
TI  - Microbiology of otitis externa.
AB  - Microbiologic and clinical data from 26 patients with otitis externa were
      prospectively evaluated. Specimens were processed for aerobic and anaerobic
      bacteria. Bacterial growth was noted in 23 specimens. A total of 33 aerobic and 2
      anaerobic bacteria were recovered. Aerobic bacteria only were isolated in 21
      (91%) patients, anaerobic bacteria only in 1 (4%), and mixed aerobic and
      anaerobic bacteria in 1 (4%). The most common isolates were Pseudomonas
      aeruginosa (14 instances), Staphylococcus aureus (7), Acinetobacter calcoaceticus
      (2), Proteus mirabilis (2), Enterococcus faecalis (2), Bacteroides fragilis (1),
      and Peptostreptococcus magnus (1). One isolate was recovered in 13 (57%)
      patients, 2 isolates in 8 (35%), and 3 isolates in 2 (9%). These data illustrate
      the polymicrobial nature of otitis externa in about half of the patients and the
      role of anaerobic bacteria in 8% of them. Further studies are warranted to
      evaluate the therapeutic implications of these findings.

PMID- 9018253
TI  - Acute mastoiditis in children: a 12-year retrospective study.
AB  - We undertook a retrospective study to examine our experience with acute
      mastoiditis over a 12-year period. Fifty-eight cases were identified in children
      aged 3 months to 15 years. Acute mastoiditis was the first evidence of otitis
      media in 54% of our patients. Pain and fever lasting for more than a median
      period of 4 days were most likely to be the harbingers of incipient acute
      mastoiditis. Streptococcus pneumoniae was the most common organism recovered from
      the cultures. All children were treated with intravenous antibiotics; 41 children
      were managed with an adjunctive drainage procedure. No statistically significant
      differences were observed between the cure rates and failure rates for children
      treated surgically with myringotomies with or without tubes and children managed
      more aggressively with mastoidectomies. One infant had bacterial meningitis.
      Cholesteatoma was diagnosed in two children. We conclude from our study that
      acute mastoiditis occurs mainly in young children and may be the first evidence
      of ear disease. Pain and fever that persist despite appropriate treatment for
      acute otitis media are the two most important symptoms. Intravenous antibiotics
      combined with myringotomy with or without tube insertion are as appropriate as
      intravenous antibiotics with mastoidectomy for initial management of acute
      mastoiditis in the absence of a subperiosteal abscess or central nervous system
      extension.

PMID- 9018254
TI  - Immunotherapy in the treatment of allergic fungal sinusitis.
AB  - Recommendations to withhold immunotherapy with fungal antigens from patients with
      allergic fungal sinusitis (AFS) have been based primarily on retrospectively
      reviewed, anecdotal case reports and theoretical considerations. A study that was
      approved by the investigational review board of our institution is ongoing in our
      department to administer immunotherapy with relevant fungal antigens to patients
      with histologically proven AFS. After 1 year, no instances of worsening of
      symptoms as a result of this therapy have been observed. Objective measurement of
      improvement has been difficult, but our initial clinical impression is that this
      treatment regimen has resulted in significant reduction in the reaccumulation of
      crusts and allergic mucin within the sinuses, has led to a reduction in the use
      of topical nasal steroids, and has made systemic steroid therapy unnecessary,
      thereby improving the quality of life of the patient. A further study of
      immunotherapy for patients with AFS is recommended, and suggestions for
      modification of the current protocol are presented.

PMID- 9018255
TI  - Closure of permanent tracheostomy in patients with sleep apnea: a comparison of
      two techniques.
AB  - A "permanent" skin-lined tracheostomy is used for patients with severe
      obstructive sleep apnea syndrome who fall, refuse, or can't tolerate continuous
      positive airway pressure. Closure of the stoma may be performed if the apnea has
      been controlled by surgeries that enlarge and stabilize the upper airway, if
      adequate weight loss occurs, or if the patient decides to accept continuous
      positive airway pressure. Two different closure techniques are compared. Sixty
      nine three-layer closures were performed in 66 patients from 1980 to 1990.
      Postoperative complications, including stridor, subcutaneous emphysema,
      pneumomediastinum, tracheal granuloma, hematoma, and respiratory arrest, occurred
      in 30% of patients, and three required reopening of their tracheostomy sites.
      After 1990 a simple deepithelialization technique was used in 10 patients without
      any major complications. This technique is simpler and quicker and can be
      performed with the patient under local anesthesia.

PMID- 9018256
TI  - Pilot study of the oral omeprazole test for reflux laryngitis.
AB  - BACKGROUND: Gastroesophageal reflux disease occasionally presents with laryngeal
      symptoms. Such patients are often referred for a gastroenterology evaluation.
      This study was designed to determine whether an empiric trial of high-dose
      omeprazole therapy could reliably identify patients with reflux laryngitis and
      thus obviate the need for a gastroenterology workup. METHODS: Patients were
      evaluated with a history, physical examination, esophageal manometry, upper
      endoscopy, and 24-hour pH-metry for determination of the presence of absence of
      underlying gastroesophageal reflux disease and then received an empiric trial of
      oral omeprazole therapy (20 mg twice daily for 1 month). A positive omeprazole
      test result was defined as resolution of all laryngeal symptoms on completion of
      the empiric trial of therapy. RESULTS: Two patients were classified as having no
      reflux, and eight were classified as having reflux. Omeprazole test results were
      positive in six patients. Five of six had reflux, but one patient had no evidence
      for reflux. Omeprazole test results were negative in four patients. Three of four
      had reflux, and one did not. Despite the absence of antisecretory therapy,
      laryngeal symptoms did not recur in either patient without reflux during follow
      up. Laryngeal symptoms were managed in two of the three patients with reflux who
      had negative omeprazole test results and who were using inhalers in combination
      with histamine H2 receptor antagonist therapy for their reflux disease. One
      patient with reflux who had a negative omeprazole test result responded to higher
      doses of omeprazole, and the five patients with reflux who had positive
      omeprazole test results all responded to continuation of omeprazole. CONCLUSIONS:
      The omeprazole test may be useful in confirming the suspicion of reflux
      laryngitis in patients suspected of having this disease after an otolaryngology
      evaluation. However, there is a potential for false-positive and false-negative
      test results. A gastroenterology evaluation may aid in the identification of
      false-positive test results by documenting the absence of reflux in certain
      responders.

PMID- 9018257
TI  - Spindle cell carcinoma of the larynx and hypopharynx.
AB  - We reviewed the clinical records of 34 patients with laryngeal (25) and
      hypopharyngeal (9) spindle cell carcinomas who were treated at our institution
      between 1960 and 1990. All the spindle cell carcinomas were studied using
      paraffin section immunostains, and we performed ploidy analysis of the
      sarcomatoid component in 31 patients. Of the 31 patients who underwent their
      initial treatment at our institution, 25 were men and 6 were women (median age at
      presentation, 64.6 years). A T1 glottic tumor, usually seen as an exophytic firm
      mass, was the most common type of tumor observed (16 cases). The spindle cells
      were nondiploid in 86% of the carcinomas, with positive keratin immunostains in
      74%. The median follow-up time was 3.7 years. Recurrence of the tumor after
      partial or total laryngectomy or pharyngectomy occurred in 10 patients. Eight
      patients died of their disease. The Kaplan-Meier estimate of surviving at least 3
      years after initial treatment was 56.8%. Keratin positivity adversely affected
      the overall survival rate (p < 0.02). The survival rate of patients with
      hypopharyngeal tumors was worse than that of patients with laryngeal lesions (p <
      0.001). The presence of keratin positivity and nondiploid DNA content in the
      spindle cell population supports the neoplastic epithelial origin of these tumors
      (sarcomatoid carcinoma). The overall tumor behavior and surgical therapy appeared
      to be comparable with those of squamous cell carcinomas at a similar stage.

PMID- 9018258
TI  - Safe pediatric outpatient sedation: the chloral hydrate debate revisited.
AB  - Diagnostic imaging in the pediatric patient frequently requires sedation. The use
      of chloral hydrate, the standard agent for many years, has recently come under
      severe scrutiny. The American Academy of Pediatrics (AAP) published guidelines
      for the elective sedation of pediatric patients; however, compliance with the AAP
      guidelines is not compulsory. A review of the medical literature shows a wide
      range of medications used for pediatric sedation, along with a diversity in the
      protocols available for monitoring the cardiopulmonary status of the patient.
      When ordering computed tomography and magnetic resonance imaging scans, pediatric
      otolaryngologists indirectly are exposing their patients to the sedation
      practices and monitoring protocols of their referral imaging center. A
      questionnaire regarding the sedation protocol for routine, outpatient, computed
      tomography or magnetic resonance imaging scans in children aged 5 years or
      younger was sent to staff radiologists at 36 pediatric medical centers throughout
      the United States. A variety of sedation practices were elicited. The complete
      survey results are presented, including monitoring practices, complication, and
      success rates. Despite concerns about its safety, chloral hydrate remains a
      frequently used and safe method of pediatric outpatient sedation.

PMID- 9018259
TI  - Altered regulation of cell surface peptidases in human cholesteatoma.
AB  - Cholesteatoma is a destructive process involving an accumulation of desquamated
      keratin arising from squamous epithelium that pathologically has invaded the
      middle ear or mastoid process. The clinical hallmarks of cholesteatomas, namely
      invasion of healthy tissues, migration, unrestrained proliferation,
      aggressiveness, recidivism, and uncoordinated differentiation predict the
      existence of defects in the normal biology and biochemistry of the cellular
      constituents that compose a cholesteatoma, as well as in the cellular
      interactions between these cells, the surrounding normal tissue, and the host. In
      the current report, we analyzed 11 cholesteatomas and matched healthy tissue for
      altered expression in four different cell surface peptidases, aminopeptidase A,
      aminopeptidase N, dipeptidyl peptidase IV, and neutral endopeptidase. We suggest
      that peptidases may modulate cell growth and differentiation by inactivating
      stimulatory signals (or conversely, by activating inhibitory signals).

PMID- 9018260
TI  - Intraoperative diagnosis of primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia refers to clinical disease attributable to
      congenitally abnormal or absent ciliary motility. Diagnosis typically requires
      electron microscopy to document aberrant axoneme ultrastructure. Electron
      microscopy, however, remains inaccurate and Inconvenient as a screening test for
      symptomatic individuals. To avoid delays in diagnosis and to ensure adequacy of
      the tissue sample, we recommend a tracheal biopsy with an intraoperative
      histologic examination of ciliary motion. This study included patients evaluated
      at our institution for recurrent or chronic upper respiratory conditions
      characterized by chronic sinusitis, chronic mucoid otitis, and chronic
      bronchitis. A tracheal mucosa biopsy sample was obtained from each patient and
      was immediately examined in the operating room using light microscopy. If the
      magnified image demonstrated normal ciliary motility, primary ciliary dyskinesia
      was excluded and electron microscopy was not ordered. In the absence of normal
      ciliary motility, the specimen was placed in glutaraldehyde and ultrastructural
      axoneme morphology was evaluated. In the last 5 years, we have evaluated ciliary
      motility in 20 patients. Three patients had abnormal ciliary motility identified
      by light microscopy, and primary ciliary dyskinesia was confirmed histologically
      in each patient. In the remaining 17 patients, normal ciliary motility was
      observed, obviating the need for electron microscopy. We advocate intraoperative
      microscopic study of ciliary motility as a rapid, simple, accurate, and
      inexpensive technique to screen patients for primary ciliary dyskinesia.

PMID- 9018261
TI  - New developments in the diagnosis of Kartagener's syndrome.
AB  - Kartagener's syndrome is characterized by the clinical triad of bronchitis,
      sinusitis, and situs inversus. An inherited ultrastructural defect results in
      ciliary immotility with impaired mucociliary clearance throughout the pulmonary
      and sinonasal passages. Until recently, the diagnosis of Kartagener's syndrome
      was made on the basis of a qualitative decrease in the number of dynein arms and
      subjective abnormalities in other ciliary components on electron microscopy. New
      investigations, however, have defined objective methods of diagnosis on the basis
      of quantitative ciliary measurements. The use of these methods in a series of 17
      cases of suspected ciliary immotility resulted in a reversal of diagnosis in 6
      cases (35%) that previously were considered normal. These results suggest that
      the prevalence of inherited ciliary dyskinesias is much greater than currently is
      recognized. The early identification and treatment of individuals with these
      disorders could lead to a reduction in irreversible sinus and pulmonary
      pathologic conditions with improved long-term survival.

PMID- 9018262
TI  - Idiopathic Dandy's syndrome.
AB  - In 1941 Dandy described patients in whom he had performed bilateral vestibular
      nerve sections who reported "jumbling" objects in their visual fields when in
      motion and difficulty walking in the dark. We use the term Dandy's syndrome to
      describe patients with bilateral vestibular loss as the cause of the above
      symptoms. The caloric response in these patients is either markedly reduced or
      absent when the cause is in the peripheral vestibular system. This study explored
      whether differences exist between those patients in whom the cause is known and
      those patients with no known cause. We reviewed our experience with 105 patients
      in whom Dandy's syndrome was diagnosed between 1984 and 1994. Information on
      their presenting symptoms, findings on physical examination, audiometric status,
      electronystagmographic findings, laboratory test results, symptom outcome, and
      cause was collected. Patients with known causes (Meniere's disease, ototoxicity,
      tumors, vascular disease, trauma, heredity, autoimmune disease, infection) were
      compared as a group with those with no known cause. Of the 105 patients 34 (32%)
      had no obvious cause for their symptoms despite an extensive evaluation. This
      group was similar to those with a known cause except for having a greater
      preponderance of women (68% vs. 41%, p = 0.018) and an increased likelihood to
      have normal audiogram findings (53% vs. 19%, p = 0.0009). All other variables,
      including age, duration of and age at onset of symptoms, physical examination,
      and electronystagmographic findings did not differ significantly between the two
      groups. Only 28% of patients with known causes and 40% (p < 0.05) of those with
      idiopathic Dandy's syndrome had improvement of their symptoms, underscoring the
      problem with rehabilitation. The results of this study are compared with earlier
      reports from our and other institutions.

PMID- 9018263
TI  - Posterior cervical rhytidectomy: a valuable adjunct in facial rejuvenation
      surgery.
AB  - OBJECTIVE: To describe the aesthetic indications and operative technique of
      posterior cervical rhytidectomy as a staged procedure after extended cervical
      facial rhytidectomy. DESIGN: The senior author's series of patients requiring
      posterior cervical rhytidectomy is reviewed, including preoperative and
      postoperative aesthetic results. SETTING: A private practice plastic surgery
      clinic. PATIENTS: Eleven patients who underwent staged posterior cervical
      rhytidectomy after extensive cervical-facial rhytidectomy are presented, with
      follow-up ranging from 3 months to 8 years. During this same duration, 941
      primary and 256 secondary cervical-facial rhytidectomies were performed.
      INTERVENTIONS: The preoperative and postoperative results are presented along
      with a description of the pertinent anatomy and the senior author's operative
      technique. Potential complications are reviewed. A discussion is included on ways
      to minimize these untoward sequelae. OUTCOME MEASURE: The aesthetic postoperative
      results are reviewed, and representative clinical photographs are presented.
      RESULTS: Staged posterior cervical rhytidectomy is a safe and effective means of
      improving certain stigmata of previous cervical-facial rhytidectomy in patients
      requiring extensive facial rejuvenation. CONCLUSIONS: Posterior cervical
      rhytidectomy is a valuable surgical adjunct in selective patients who demonstrate
      redundant skin and soft tissue in the posterior cervical region.

PMID- 9018264
TI  - Ovine fetal laryngeal chemoreflex thresholds and respiratory effects.
AB  - In newborn infants, laryngeal contact with solutions of low chloride
      concentration or pH evokes swallowing, laryngeal adduction, and respiratory
      inhibition (laryngeal chemoreflex). To determine whether the laryngeal
      chemoreflex is present during fetal life and its effect on fetal respiratory
      activity, eight time-bred ewes (128 +/- 2 days) were prepared with fetal
      electrocortical diaphragm and esophageal electrodes and a nasopharyngeal
      catheter. After a 60-minute control period, increasing volumes (0.1 to 1.0 ml/kg)
      of 0.15 mol/L NaCl or distilled water (0.05 to 1.0 ml/kg) and decreasing
      concentrations of NaCl (0.15 to 0.02 mol/L) at a fixed volume (0.3 ml/kg) were
      sequentially administered through the nasopharyngeal catheter (38 degrees C). The
      minimum water volume that stimulated swallowing was significantly less than the
      minimum 0.15 mol/L NaCl volume (0.10 +/- 0.02 vs. 0.70 +/- 0.05 ml/kg). The
      maximum NaCl concentration that stimulated swallowing was 0.04 +/- 0.01 mol/L
      During the control period, respiratory activity averaged 14.6 +/- 0.7
      breaths/minute and did not change during absent swallow responses or isotonic
      saline-induced swallows. However, respiratory activity significantly decreased
      during water (4.7 +/- 0.6 breaths/minute) and hypotonic saline-induced swallow
      responses (3.7 +/- 0.7 breaths/minute). Fetal electrocortical activity did not
      change during absent or stimulated swallows. We conclude that laryngeal water or
      hypotonic saline solution may stimulate fetal swallowing and suppress fetal
      respiratory activity, similar to the newborn laryngeal chemoreflex. We speculate
      that an exaggeration of the laryngeal chemoreflex apnea response in the newborn
      may predispose to sudden infant death syndrome.

PMID- 9018265
TI  - Endoscopically introduced expandable stents in laryngotracheal stenosis: the jury
      is still out.
AB  - A new technique using endoscopically introduced, expandable stents for the
      management of upper airway stenosis is presented. Evaluation of this technique in
      the canine model forms the basis of this pilot study. Stenosis was surgically
      induced in a controlled fashion by resection of cartilage from the anterior
      cricoid arch and tracheal wall to reduce the airway diameter by approximately
      50%. A period of 8 weeks was allowed for complete healing and maturation of the
      surgical stenosis. This was followed by endoscopic introduction of expandable
      titanium-mesh stents. The stents were then balloon-inflated to dilate the
      stenotic region. Airway patency was assessed clinically, radiologically, and
      endoscopically, before expansion and at 4 and 8 weeks after expansion. This
      assessment was followed by euthanasia of the animals and gross examination of the
      expanded stenotic segments. In general, the stents were well tolerated with
      adequate expansion of the airway. In some instances granulation tissue formation
      was noted around the stents. This was less pronounced when stents coated with
      Tecoflex (Advanced Surgical Intervention Co., San Clemente, Calif.) were used.
      This is probably because of their "inert" nature, which induces less tissue
      reaction. A literature review of the subject is presented. The significance of
      this endoscopic modality for management of upper airway stenosis is discussed,
      and the indications, alternatives, potential pitfalls, and complications are
      depicted.

PMID- 9018266
TI  - Meningitis after cochlear implantation in Mondini malformation.
AB  - Although the potential for CSF leakage and subsequent meningitis after cochlear
      implantation in the malformed cochlea has been recognized, this complication has
      not been previously reported. We report a case of CSF otorhinorrhea and
      meningitis after minor head trauma developing 2 years after cochlear implantation
      in a child with Mondini malformation. Leakage of CSF was identified from the
      cochleostomy around the electrode of the implant, and this leak was sealed with a
      temporalis fascia and muscle plug. Although this complication appears to be rare,
      care must be taken to seal the cochleostomy in children with inner ear
      malformations at the initial surgery, and any episode of meningitis after surgery
      must be thoroughly investigated to rule out CSF leakage from the labyrinth.

PMID- 9018267
TI  - Immunosuppression and systemic lupus erythematosus predisposing to laryngeal
      abscess.

PMID- 9018268
TI  - Nontuberculous mycobacterial infection of the frontal sinus in a child.

PMID- 9018269
TI  - Successful tracheoesophageal puncture voice restoration in a patient with total
      glossectomy.

PMID- 9018270
TI  - Tracheoesophageal fistula and sinusitis from invasive aspergillosis.

PMID- 9018271
TI  - Translaryngeal puncture in a collegiate fencer.

PMID- 9018272
TI  - Tracheal agenesis: a case report and review of the literature.

PMID- 9018273
TI  - Bifid epiglottis and polydactyly: a new genetic syndrome.

PMID- 9018274
TI  - Pediatric subacute acetaminophen toxicity.

PMID- 9018275
TI  - Capillary hemangioma of the tympanic membrane.

PMID- 9018276
TI  - Relapsing polychondritis.

PMID- 9018277
TI  - Pleomorphic adenoma of the trachea.

PMID- 9018278
TI  - Medicare beneficiaries need new care options, better protection: IOM.

PMID- 9018279
TI  - Federal guidelines needed to ensure safety in animal-human transplants.

PMID- 9018280
TI  - Child abuse doubles; investigation lags.

PMID- 9018281
TI  - Better records needed for Gulf veterans' health research.

PMID- 9018282
TI  - The complicated task of monitoring vaccine safety.
AB  - Vaccination is an essential component of modern public health programs and is
      among our most cost-effective medical interventions. Yet despite vaccines' clear
      effectiveness in reducing risks of diseases that previously attacked large
      proportions of the population, caused many deaths, and left many people with
      permanent disabilities, current vaccination policies are not without controversy.
      Vaccines, like all other pharmaceutical products, are not entirely risk-free;
      while most known side effects are minor and self-limited, some vaccines have been
      associated with very rare but serious adverse effects. Because such rare effects
      are often not evident until vaccines come into widespread use, the Federal
      government maintains ongoing surveillance programs to monitor vaccine safety. The
      interpretation of data from such programs is complex and is associated with
      substantial uncertainty. A continual effort to monitor these data effectively and
      to develop more precise ways of assessing risks of vaccines is necessary to
      ensure public confidence in immunization programs.

PMID- 9018283
TI  - Managed care and the public health challenge of TB.
AB  - Managed care is fast becoming the dominant form of medical care delivery and
      financing in the United States, yet its effects on public health practice remain
      largely unknown. Tuberculosis (TB) is a classic example of a disease with both
      public health and medical care implications, and as such it provides an
      opportunity for examining the impact on public health of the shift towards
      managed care in the medical marketplace. The authors approach the role of managed
      care in TB control by first considering the need for interorganizational
      coordination at the community level. The authors identify four basic models of
      how managed care organizations may fit into TB control efforts in local
      communities, using observations from 12 local public health jurisdictions to
      illustrate these models. These TB control models provide insight into the general
      mechanisms through which managed care organizations may affect other areas of
      public health practice.

PMID- 9018284
TI  - Defining research when it comes to public health.

PMID- 9018285
TI  - Public confidence in public health research ethics.

PMID- 9018286
TI  - Sickle cell disease expenditures and outcomes.

PMID- 9018287
TI  - Cost of hospitalizations associated with sickle cell disease in the United
      States.
AB  - OBJECTIVE: This study estimated the number and cost of hospitalizations
      associated with sickle cell disease in the United States. METHODS: To estimate
      the number of hospitalizations per year in the United States of people with
      sickle cell disease, the authors used data for the years 1989 through 1993 from
      national hospital discharge surveys conducted by the National Center for Health
      Statistics. The authors derived cost estimates using data from a 1992 national
      hospital discharge survey conducted by the Agency for Health Care Policy and
      Research and a 1992 survey of physicians conducted by the American Medical
      Association. RESULTS: During the years 1989 through 1993, there were on average
      an estimated 75,000 hospitalizations per year of children and adults with sickle
      cell disease. The average direct cost per hospitalization (in 1996 dollars) was
      estimated at $6300, for a total direct cost of $475 million per year. In 66% of
      hospital discharge records, government programs were listed as the expected
      principal source of payment. CONCLUSIONS: The cost of hospitalizations associated
      with sickle cell disease is substantial. Because government programs pay most of
      this cost, further government-funded research to develop interventions that
      prevent complications of the disease has great potential for cost savings as well
      as for reducing the suffering of those afflicted with this painful genetic
      disorder. These national cost estimates contribute to an understanding of the
      impact of sickle cell disease and should be useful in establishing research
      priorities.

PMID- 9018288
TI  - Hospital utilization patterns and costs for adult sickle cell patients in
      Illinois.
AB  - OBJECTIVES: To determine population size, demographic characteristics, hospital
      utilization patterns, the specialties of physicians providing care, and costs for
      hospitalized adult sickle cell patients in Illinois. METHODS: A statewide,
      administrative dataset for the two-year period from january 1992 through December
      1993 was analyzed retrospectively. RESULTS: There were 8403 admissions among 1189
      individual sickle cell patients for the two-year period. Eighty-five percent of
      patients resided in the Chicago metropolitan area. The median age of the 1189
      patients was 29; two-thirds had Medicaid or Medicare coverage. Emergency
      departments were the primary source of admissions (85.7%). The most common
      admitting diagnosis was painful crisis (97.4%), and average length of stay was
      four days. The median number of admissions per patient was three; most patients
      (85%) used only one or two hospitals. A small group used more than four hospitals
      and accounted for 23% of statewide admissions. Primary care physicians cared for
      most patients, and total hospitalization charges were more than $59 million.
      CONCLUSIONS: In Illinois the adult sickle cell population is concentrated in
      major urban centers, primarily the Chicago metropolitan area. These patients
      accounted for approximately 8400 admissions and more than $59 million in hospital
      charges during the two-year study period. A small group of patients used multiple
      hospitals and accounted for more than 23% of total hospitalization charges. This
      study shows the necessity of and provides a useful framework for developing
      targeted programs for adult sickle cell patients as well as for training
      physicians to efficiently provide comprehensive health care services for this
      population.

PMID- 9018289
TI  - Geographic differences in mortality of young children with sickle cell disease in
      the United States.
AB  - OBJECTIVES: Because geographic differences in health care have been found for
      many diseases, including those affecting children, there are probably geographic
      differences in the health care of young children with sickle cell disease.
      Consequently, survival of young children with sickle cell disease might differ
      among geographic areas. This study's objective was to identify areas in the
      United States where young children with sickle cell disease are at especially
      high and low risk of dying. METHODS: Using U.S. death certificate data from 1968
      through 1992, the authors calculated the mortality rates of 1- through 4-year-old
      black children with sickle cell disease for states, counties, and cities. Deaths
      from trauma, congenital anomalies, and perinatal conditions were excluded.
      RESULTS: From 1968 through 1980 and from 1981 through 1992, 1- through 4-year-old
      black children with sickle cell disease in Florida had a markedly higher risk of
      dying, and those in Pennsylvania had a markedly lower risk of dying, than the
      average 1- through 4-year-old black child with the disease in the United States.
      From 1981 through 1992, 1- through 4-year-old black children with sickle cell
      disease in Maryland had the lowest mortality rate in the nation. During the same
      time period, 1- through 4-year-old black children with sickle cell disease in
      five counties in Florida were at especially high risk, while in Baltimore no
      young black children with the disease died. These geographic differences in
      mortality of black children with sickle cell disease greatly exceeded geographic
      differences in mortality of black children without the disease. CONCLUSIONS:
      Marked differences exist across the United States in mortality of young black
      children with sickle cell disease. To improve survival for children with the
      disease in high mortality areas, evaluations should be made of the accessibility
      and quality of medical care, and of parents' health care seeking behavior and
      compliance with antibiotic prophylaxis. In addition, efforts should be made to
      understand and duplicate the success of treatment programs in low mortality
      areas.

PMID- 9018290
TI  - Risk factors for seabather's eruption: a prospective cohort study.
AB  - OBJECTIVE: A prospective cohort study was performed to identify risk factors for
      seabather's eruption. METHODS: Study participants were recruited at four beaches
      in Palm Beach County, Florida, during three weekends of May and June 1993.
      Participants were interviewed by telephone after 48 hours regarding medical
      history, beach activities, development of rashes, and use of possible preventive
      measures. RESULTS: Seabather's eruption, defined by the occurrence of a rash
      within two days of exposure to seawater, was reported by 114 (16%) of 735
      respondents. The strongest predictor of seabather's eruption was a past history
      of the condition. Children less than 16 years of age were also at increased risk,
      as were surfers. Showering with one's bathing suit off was a useful protective
      measure. CONCLUSION: The study's findings suggest that when the seasonal risk of
      seabather's eruption is present, children, people with a history of seabather's
      eruption, and surfers are at greatest risk. During the sea lice season,
      seabathers can minimize their risk by showering with their bathing suits off
      after seabathing. Length of the time spent in water was not significantly
      associated with seabather's eruption.

PMID- 9018291
TI  - Preventing hepatitis B in people in close contact with hepatocellular carcinoma
      patients.
AB  - OBJECTIVE: To determine the prevalence of testing for hepatitis B virus (HBV)
      infection in the clinical management of primary liver cancer (hepatocellular
      carcinoma). METHODS: The authors reviewed the records of 78 patients treated for
      hepatocellular carcinoma in hospitals in the Puget Sound area in 1988 and early
      1989 and reviewed all 1990 U.S. death certificates on which primary liver cancer
      was listed. RESULTS: The records of 50 (64%) of 78 hepatocellular carcinoma
      patients contained no evidence that the patient's hepatitis B surface antigen
      (HBsAg) status had been determined. In addition, of 4353 people who died in 1990
      for whom the diagnosis of primary liver cancer was listed on the death
      certificate, HBV infection was also listed for only 136 (3%), much less than
      expected based on case series. CONCLUSIONS: Many patients with hepatocellular
      carcinoma are not tested for HBV infection, suggesting that their close contacts
      are also not evaluated for HBV infection and the need for vaccination. Hepatitis
      B vaccination of close personal contacts of HBV-infected hepatocellular carcinoma
      patients is an important strategy for preventing HBV transmission.

PMID- 9018292
TI  - Tuberculosis beliefs among recent Vietnamese refugees in New York State.
AB  - OBJECTIVE: To identify newly arrived Vietnamese refugees' beliefs about
      tuberculosis (TB) and TB education needs. METHODS: In 1994, the New York State
      Health Department and the Centers for Disease Control and Prevention conducted a
      survey of 51 newly arrived adult Vietnamese refugees in two New York counties.
      After being trained in interview methods, two bilingual researchers asked 32 open
      ended questions on the causes of TB, TB treatment, and the disease's impact on
      work and social relationships. RESULTS: Respondents correctly viewed TB as an
      infectious lung disease with symptoms such as cough, weakness, and weight loss.
      Hard manual labor, smoking, alcohol consumption, and poor nutrition were believed
      to be risk factors. Many respondents incorrectly believed that asymptomatic
      latent infection is not possible and that infection inevitably leads to disease.
      Nearly all respondents anticipated that having tuberculosis would adversely
      impact their work, family, and community activities and relationships.
      CONCLUSIONS: Targeted patient education is needed to address misconceptions about
      TB among Vietnamese refugees and to help ensure adherence to prescribed treatment
      regimens.

PMID- 9018293
TI  - Swimming pool drownings and near-drownings among California preschoolers.
AB  - OBJECTIVE: To describe a significant but poorly understood public health problem,
      the authors compiled data on swimming pool drownings and near-drownings requiring
      hospitalization for California children ages 1 to 4. METHODS: Data from death
      certificates were used to analyze swimming pool drownings, and hospital discharge
      data were used to analyze near-drownings. RESULTS: Among California preschoolers
      in 1993, pool immersion incidents were the leading cause of injury death and the
      eighth leading cause of injuries leading to hospitalization. Rates per 100,000
      population were 3.2 for fatalities and 11.2 for nonfatal incidents, with a
      fatality-to-case ratio of 1:3.5. Total charges for initial hospital stays
      (excluding physicians' fees) were $5.2 million for 1227 hospital days.
      CONCLUSIONS: Swimming pools remain a serious hazard for young children. Primary
      prevention continues to be an important public health goal. Public health
      officials should support the adoption of laws designed to protect children from
      drowning and near-drownings.

PMID- 9018294
TI  - Stalking the next epidemic: ProMED tracks emerging diseases.

PMID- 9018295
TI  - Drug abuse control under FDA, 1938-1968.

PMID- 9018296
TI  - Moving travel medicine.

PMID- 9018297
TI  - Travel advice: a study among Swiss and German general practitioners.
AB  - Travelling to tropical and subtropical destinations is common among European
      citizens. Many of them consult their general practitioners (GPs) for pre-travel
      advice. Little is known about the knowledge, the sources of information and the
      needs of physicians. One hundred and fifty Swiss and I50 German GPs giving travel
      advice were interviewed using pretested telephone interviews and questionnaires
      to assess their knowledge about travel advice to be given for 2 frequent holiday
      destinations (Kenya and Thailand), and to ask which information sources were
      available to them. Ninety-six per cent and 89%, respectively, of GPs in 2
      neighbouring areas of Switzerland and Germany gave travel advice to their
      clients. In telephone interviews, standard recommendations on malaria medication,
      as approved by the national travel advice committees, were stated by 45 and 25%
      of Swiss GPs, and 22 and 9% of German GPs for Kenya and Thailand. The figures for
      correct advice on vaccination requirements were 23 and 47% for the Swiss GPs, and
      2 and 25% for the German GPs. Half of the GPs wanted to consult their documents
      before giving advice. The main source of information used by Swiss GPs was the
      monthly updated Bulletin of the Federal Office of Public Health (BFOPH). A
      variety of different sources was recorded among German practitioners. Regular,
      concise information on travel advice tops the list of requested information
      material in both countries. The extent of correct pre-travel advice is
      unsatisfactory in both study groups. Use of standardized, regularly updated and
      readily available sources of information on travel advice for the GP could avoid
      uncertainties of both the provider and the recipient of advice.

PMID- 9018298
TI  - Susceptibility of Ugandan Trypanosoma brucei rhodesiense isolated from man and
      animal reservoirs to diminazene, isometamidium and melarsoprol.
AB  - Thirty-six Trypanosoma brucei spp. stocks isolated from man and domestic animals
      in south-east Uganda were studied for susceptibility to diminazene, isometamidium
      and melarsoprol in vitro. All stocks were susceptible to melarsoprol. One T.b.
      rhodesiense stock isolated from a sleeping sickness patient showed reduced
      susceptibility to the veterinary drugs diminazene and isometamidium. More than
      100 ng/ml diminazene or 0.78 ng/ml isometamidium were required to eliminate that
      stock during 10 days drug exposure. In contrast, the remaining stocks were
      eliminated by 0.8-6.3 ng/ml diminazene and 0.01-0.20 ng/ml isometamidium. Clones
      derived from the resistant T. b. rhodesiense stock showed reduced susceptibility
      to isometamidium and diminazene comparable to the parental population. Control of
      sleeping sickness by treatment of the animal reservoir could, therefore, face
      serious problems since drug-resistant stocks as reported here would most likely
      not be eliminated by recommended doses of diminazene and isometamidium.

PMID- 9018299
TI  - Trypanocidal effect of Ir-(COD)-pentamidine tetraphenylborate on Trypanosoma
      brucei and T. b. gambiense rodent models and serum kinetics in sheep.
AB  - Pentamidine di-(iridium cyclo-octadiene)tetraphenylborate, called Ir-(COD)
      pentamidine tetraphenylborate, was selected from a primary screening as a
      promising trypanocidal compound. The compound was evaluated against three
      isolates: Trypanosoma brucei brucei CMP, T.b. brucei GVR 35 and T.b. gambiense
      Feo. On the T.b. brucei GVR 35 murine CNS model, no mouse was cured when the
      treatment was commenced 21 days post-infection whatever the treatment regimen.
      Nevertheless, in vitro the compound killed the trypomastigote forms of T. b.
      gambiense Feo at 0.6 microM. In vivo, the compound cured all mice infected 1 hour
      previously with T. b. gambiense Feo after a 10 mg/kg (6.3 mumol/kg) treatment
      subcutaneously administered in a single dose. Moreover, the compound was active
      at 1 mg/kg (0.6 mumol/kg) in a single dose against the early stage of the T. b.
      brucei Antat 1-9 sheep model. Serum kinetics data showed that pentamidine di
      (iridium cyclo-octadiene) tetraphenylborate was distributed within deep
      compartment according to a monocompartmental model. The maximum iridium serum
      concentration was 198 micrograms/l corresponding to 1 mumol/kg of iridium
      derivative and this value remained stable for 30-50 hours post-treatment. Iridium
      was completely eliminated from the serum 700 hours post-treatment. all data
      obtained from these models are in favour of an activity in the early stage of the
      disease but indicate that the compound could not cross the blood-brain barrier
      despite its lipophilicity. Although iterative treatments with the compound
      rapidly induced the selection of iridium derivative refractory populations, the
      compound could be studied on pentamidine refractory strains.

PMID- 9018300
TI  - Changes in the pattern of infant and childhood mortality in upper river division,
      The Gambia, from 1989 to 1993.
AB  - A surveillance system was used to detect births and deaths in children in a
      large, rural, West African population from 1989 to 1993. Cause of death was
      investigated using post-mortem questionnaires. Overall infant (age 0-11 months)
      and child (age 1-4 years) mortality rates of 80.1 and 18.8 per 1000 per year were
      recorded. These were reasonably consistent over the period of surveillance. The
      most frequent cause of death in infants was acute respiratory infection (ARI),
      whereas in children it was malaria: these two conditions accounted for 41% of the
      deaths in children under 5 years old. Other leading causes of death were acute
      gastroenteritis, malnutrition, and septicaemia. Deaths attributed to ARI
      decreased over the 5-year period, but mortality rates from other causes were
      either unchanged or increased slightly. Mortality from all causes peaked in the
      rainy season and was slightly higher in villages which were part of a primary
      health care programme than in those which were not. There were also no
      differences between male and female mortality rates beyond one year of age.
      Despite the introduction of a number of health interventions, there has been no
      major change in the overall pattern of mortality in children in a rural area of
      The Gambia. Malaria and ARI remain the main causes of death.

PMID- 9018301
TI  - Effects of cow's milk supplementation on milk output of protein deficient
      lactating mothers and on their infants' energy and protein status.
AB  - A cow's milk supplement providing 500 kcal (2093 kJ) and 18 g of protein a day
      was given during 2 months to 83 lactating Zairian mothers suffering from protein
      malnutrition. The mothers' nutritional status improved significantly after 2
      months. The initial 24-hour mother's milk output was on average 607 ml (s.d.:
      182) and did not change significantly after 2 months (604 ml; s.d.: 178). Initial
      milk output and change in milk output did not differ according to mothers'
      nutritional status at inclusion. Breast-fed infants showed a significant
      improvement of their mean serum albumin concentration while their growth was
      similar to the mean growth of children of the same age.

PMID- 9018302
TI  - Asking questions about women's reproductive health: validity and reliability of
      survey findings from Istanbul.
AB  - In countries where population-based data on health problems are scarce, the
      extent of reproductive morbidity can be estimated from replies in structured
      interviews as a complement or as an alternative to reports from physician's
      examination and laboratory tests. We examined the sensitivity and specificity of
      detected morbidity based on these replies as compared to medical diagnoses and
      explored the consistency of replies when the questionnaire was administered
      twice, by two types of interviewers in different environments. Data were
      collected in a cross-sectional survey in Istanbul. The presence or absence of
      five morbidities, reproductive and urinary tract infections (RTI and UTI),
      menstrual disorders, pelvic relaxation and anaemia was determined by algorithms
      based on the replies, and by the physician's diagnosis. Except with anaemia,
      questionnaire replies were more specific than sensitive in detecting morbidity,
      probably partly due to many morbid conditions being accepted as normal.
      Sepcificity exceeded 80% for home reports of menstrual disorders (93.0%), pelvic
      relaxation (95.7%), RTI (abnormal discharge and pain) (81.2%) and UTI (80.7%),
      with the corresponding figure for anaemia at 41.7%; the best sensitivity results
      were for anaemia (58.3%), RTI (abnormal discharge only) (49.3%) and menstrual
      disorders (45.4%) with figures for pelvic relaxation and UTI reaching only 17.3
      and 13.0%. Reliability between the interviews (assessed by the K coefficient),
      was highest at 66.1% for pelvic relaxation and lowest at 39.9% for menstrual
      disorders. Reliability varied between the two lay interviewers, suggesting the
      interviewer and the interview conditions are important. Questionnaire-based
      information on this type of morbidity is most useful for ascertaining perceived
      ill-health and only of limited use for the corresponding medically defined
      conditions.

PMID- 9018303
TI  - Epidemiology of syphilis in pregnancy in rural South Africa: opportunities for
      control.
AB  - The paper describes the epidemiology, risk factors and impact on pregnancy
      outcome of syphilis in pregnant women in rural South Africa. Prevalence was
      determined from laboratory records. A case-control study of 200 women (50 cases
      with syphilis) was done to investigate possible risk factors. To determine the
      impact on pregnancy outcome, and to evaluate the effect of treatment, a
      retrospective cohort was constructed. Overall prevalence of syphilis was 6.5%; it
      was highest in the urban antenatal clinic (9%). The odds ratios for syphilis in
      women gravidity 3-5 compared to gravidity 6 was 3.2 and 2.3 compared to women
      with gravidity 2 or less. For women with a previous birth, those with a previous
      perinatal death were 3.2 times more likely to have syphilis after adjusting for
      other risk factors. Pregnancy outcome was available for 187 women. The adjusted
      odds ratio of an adverse pregnancy outcome in women with syphilis was 11.8. All
      still births occurred in women with syphilis. The prevalence of syphilis is high
      in this rural area and screening should be applied to all women. Although
      screening was comprehensive, less than half of the detected cases were fully
      treated and a poor perinatal outcome ensued. On-site testing for syphilis at the
      time of booking would allow treatment to start immediately.

PMID- 9018304
TI  - A systematic review on the treatment of giardiasis.
AB  - To assess the efficacy of treatment of parasitological excretion of cysts and
      trophozoites and symptoms of patients with giardiasis, a systematic review of
      published randomized clinical trials was conducted through extensive searches in
      Medline, Embase and Current Contents from 1966 till 1996 as well as manual
      reviews of 28 journals. The methodological quality of all trials was assessed by
      guidelines of the Cochrane Collaboration. Thirty-one trials were included, only
      one of which had no serious methodological flaws. The mean score of
      parasitological examination was 4.8 out of a possible 15. There was a
      considerable effect in cure rate of treatment versus placebo (odds 9.3, 95% CI
      4.69-18.4), but all 3 trials in this comparison had serious flaws. Metronidazole
      treatment over more than 3 days seems to achieve a better parasitological cure
      rate than other long treatment courses (pooled odds 2.6, 95% 1.7-3.8), but trials
      are clinically and statistically heterogeneous. Single-dose therapy is as
      effective as longer treatment courses (pooled odds 0.67, 95% 0.31-1.44). Within
      the single-dose regimens tinidazole (2 g) reaches a higher parasitological cure
      rate than other short therapies (pooled odds 55, 95% CI 3.7-8.3) with relatively
      few side-effects. Placebo-controlled trials with parasitological and clinical
      outcomes are needed.

PMID- 9018305
TI  - An evaluation of dipstick-dot immunoassay in the detection of antibodies to HIV-1
      and 2 in Zimbabwe.
AB  - There is a need, in many developing countries, for simple and inexpensive HIV
      serology tests for use at the district level of health care. The Programme for
      Appropriate Technology in Health has developed a simple dipstick ELISA to detect
      antibodies to HIV-1 and 2, at a cost considerably lower than current ELISAs,
      which requires no specialized washing or reading equipment. In order to evaluate
      this dipstick under local conditions we used a panel of 546 sera selected from
      frozen stocks maintained by the Zimbabwe AIDS Prevention Project in Harare,
      Zimbabwe. Prior to storage, the sera had been tested by Abbott recombinant
      peptide HIV-1 and 2 ELISA and Enzygnost synthetic peptide HIV-1 and 2 ELISA. The
      panel included sera that were positive by both (including symptomatics and
      asymptomatics), negative by both, and sera showing discrepant test results. The
      panel was not representative of a "normal' batch of sera in Zimbabwe, and in
      particular included an abnormally high number of sera showing discrepant results.
      Thawed sera were retested using the Abbott recombinant peptide HIV-1 and 2 ELISA
      and concurrently with the synthetic peptide ICL-Dipstick ELISA. Both the
      sensitivity and specificity of the ICL Dipstick exceeded 99% when using sera that
      were positive or negative in all 3 plate ELISAs as the gold standard. When using
      sera that gave discrepant results between the two pre-storage ELISAs, most
      results with the ICL Dipstick concurred with findings from other test systems,
      including Western blot and p24 antigen detection. Considering the accuracy, low
      cost and case of operation of the ICL Dipstick ELISA, this test can be
      recommended for use for the rapid detection of antibodies to HIV at district
      level in developing countries.

PMID- 9018306
TI  - Risk factors for optic nerve disease in communities mesoendemic for savannah
      onchocerciasis, Kaduna State, Nigeria.
AB  - Ophthalmic examinations on 6831 individuals aged 5 years or more, living in 34
      guinea savannah communities mesoendemic for onchocerciasis, in Kaduna State,
      Nigeria, revealed a relatively high prevalence (9%) of optic nerve disease (OND).
      Further investigations were performed to determine what proportion of this burden
      of OND might be due to onchocercal infection. Information on history of cerebro
      spinal meningitis (CSM), past use of diethylcarbamazine (DEC) and chloroquine,
      consumption of cassava and locally produced alcohol was collected for all
      individuals by questioning. In addition, a nested case-control study of 81 cases
      of OND and 136 age and sex-matched controls was performed to investigate whether
      syphilis or a variety of other neurological disorders were responsible for a
      substantial proportion of cases of OND. Our data suggest that in this population,
      onchocercal infection is the single most important cause of OND and may account
      for 50% of all cases. Some 13% of cases were associated with signs suggestive of
      glaucoma. DEC use might be responsible for up to 30% of all OND. We found no
      evidence to suggest that any of the following are important causes of OND in the
      communities studied: CSM, syphilis, neurological syndromes such as polyneuropathy
      or other generalized neurological disease, consumption of raw cassava,
      consumption of locally prepared alcohol.

PMID- 9018307
TI  - Ethnic diversity and disease surveillance: Guinea worm among the Fulani in a
      predominantly Yoruba district of Nigeria.
AB  - Guinea-worm eradication has been progressing internationally and efforts at case
      containment have begun in most endemic countries. Case containment rests on the
      assumption that in previous phases of eradication most if not all endemic
      settlements have been identified. Experiences in the predominantly Yoruba
      communities of Ifeloju Local Government Area (LGA) in Oyo State, Nigeria,
      however, have shown that the settlements of ethnic minority groups may be
      overlooked during initial case searches and subsequent programmes of village
      based reporting. The migrant cattle-herding Fulani are found throughout the
      savannah and sahel regions of West Africa. Nearly 3000 live in 60 settlements in
      Ifeloju. An intensive case search identified 57 cases in 15 settlements. The
      assumption that village-based health workers (VBHWs) in neighbouring Yoruba farm
      hamlets would identify cases in the Fulani settlements, known as gaa, proved
      false. Only 5 endemic gaa were located next to a Yoruba hamlet that had a VBHW,
      and even then the VBHW did not identify and report the cases in the gaa. Efforts
      to recruit VBHWs for each endemic gaa are recommended, but only after LGA staff
      improve the poor relationship between themselves and the Fulani, whom they view
      as outsiders. The results also imply the need for Guinea worm eradication staff
      in neighbouring LGAs, states and countries to search actively for the disease
      among their minority populations.

PMID- 9018308
TI  - Acanthocheilonema viteae: vaccination with irradiated L3 induces resistance in
      three species of rodents (Meriones unguiculatus, Mastomys coucha, Mesocricetus
      auratus).
AB  - Three species of rodents were immunized with 50 irradiated (35 krad) stage-3
      larvae (L3) of the filaria Acanthocheilonema viteae and challenged with an
      infection of normal L3. The immunization induced a significant reduction of the
      worm burden developing from the challenge infection in all host species, the jird
      (Meriones unguiculatus), the multimammate rat (Mastomys coucha) and the golden
      hamster (Mesocricetus auratus). The induced resistance was highest in jirds (92.5
      +/- 9.7) followed by golden hamsters (59.4 +/- 26.6) and multimammate rats (55.1
      +/- 40.4). The time course of antibody response against antigens of L3, adult
      worms and microfilariae, as studied by ELISA, showed quantitative and qualitative
      differences between the species. The antibody response against L3 antigens in
      immunoblots was similar in all species. Only one of the golden hamsters developed
      an antibody response against the surface of vector derived L3, while sera of
      jirds and multimammate rats did not react with L3 surface.

PMID- 9018309
TI  - A new diagnostic test for Gaucher disease suitable for population screening.
AB  - A new test for the diagnosis of Gaucher disease is described. The test is
      designed to screen large numbers of clinical specimens from high-risk
      populations. It consists of duplex PCR amplification of genomic DNA followed by
      hybridization to alkaline phosphatase-conjugated allele-specific oligonucleotide
      probes (ASOs). High melting temperature PCR primers were used to increase
      specificity and eliminate the need for a separate annealing step. All
      hybridization and washing steps were performed at one temperature.
      Chemiluminescent detection of signals is fast, and results are easily interpreted
      directly from x-ray films. Currently, the test is being used in our laboratories
      to screen Ashkenazi Jewish populations in whom Gaucher disease is common.

PMID- 9018310
TI  - Development of a sensitive PCR to detect allele loss in a model hematopoietic
      neoplasm.
AB  - Loss or gain of an entire chromosome and interstitial deletions or amplifications
      are hallmarks of several hematopoietic neoplasms. These chromosomal anomalies can
      be identified by conventional cytogenetic analysis of bone marrow aspirates. We
      have developed a PCR-based assay to detect loss of chromosome 5q31 loci, in the
      model system of myeloid disorders with the 5q- chromosome (interstitial deletion
      of 5q), by taking advantage of a highly polymorphic dinucleotide repeat within
      the interleukin-9 (IL9) gene on 5q31. In a given sample, quantitation of
      amplification of individual alleles in a Phosphorimager allowed the
      representation of alleles to be expressed as a ratio of the larger to the smaller
      allele. Comparison of these ratios in paired DNA samples from Ficoll buoyant and
      pelletted fractions provides evidence for allele loss. Results presented here
      demonstrate that this technique of comparison of ratios of isotope incorporation
      could be expanded to Investigate any deletion or numerical abnormality in
      hematopoietic tumors.

PMID- 9018311
TI  - Determining relative microsatellite allele frequencies in pooled DNA samples.
AB  - Accurate quantification of relative allele frequencies in pooled DNA samples can
      be carried out for microsatellite markers having a dinucleotide repeat unit,
      conditional on the absence of overlapping "shadow" bands. This provides a basis
      for extending DNA pooling to this useful class of DNA marker. Expressions for the
      standard error of densitometric estimates of allele frequencies from pooled
      samples are presented, and their statistical application is illustrated in a
      variety of situations. This enables DNA pooling to be utilized in situations
      requiring the testing of statistical hypotheses concerning differences in allele
      frequencies between populations, or samples.

PMID- 9018312
TI  - PCR with end trimming and cassette ligation: a rapid method to clone exon-intron
      boundaries and a 5'-upstream sequence of genomic DNA based on a cDNA sequence.
AB  - We described a method for PCR amplification of unknown flanking genomic DNA
      fragments. This method is a combination of PCR with "end-trimming method" and
      "cassettes and cassette-primers method". In this method, genomic DNA was digested
      with three different groups of restriction enzymes. DNA in group 1 was digested
      with BamHI, BglII, FbaI, or MboI. DNA in group 2 was digested with BlnI, NheI,
      SpeI, or XbaI. DNA in group 3 was digested with SalI or XhoI. Digested DNA in
      each group was end-trimmed with Klenow fragment of DNA polymerase I in the
      presence of only one dNTP; dGTP, dCTP, and dTTP for group 1, 2, and 3,
      respectively. The synthesized cassettes, C1, C2, and C3, had 5'protruding
      sequences of 5'-ATC-3',5'-TAG-3', and 5'-CGA-3', respectively. Each compatible
      cassette was ligated to the end-trimmed DNAs in group 1-3, respectively. Nested
      PCR was then performed using an end-trimmed and cassette-ligated DNA as a
      template. Primers annealing to known sequences and cassettes were used for the
      nested PCR. The amplified DNA fragments were electrophoresed on a polyacrylamide
      gel and purified. The sequences of the DNA fragments were determined after
      cloning into pBluescript.

PMID- 9018313
TI  - A novel method to quantitate methylation of specific genomic regions.
AB  - A new solid-phase primer extension method has been developed for the quantitation
      of methylation differences and is described here. The method is less cumbersome
      than Southern blot analysis, expresses the results in a numerical format, can be
      adapted to a microtitration well format, and thus allows the analysis of a large
      series of samples. The model gene analyzed here is the calcitonin gene, but the
      method can be adapted to the analysis of methylation alterations in any area of
      the genome. The primer extension method clearly differentiated hypermethylated
      samples from normally methylated samples and a range for normal values could be
      determined. In quantitation experiments the method showed linearity in a range
      from 2% to 100% malignant blasts diluted with normal leukocytes.

PMID- 9018314
TI  - Computing genetic similarity coefficients from RAPD data: the effects of PCR
      artifacts.
AB  - Random amplified polymorphic DNA (RAPD) markers have been used for many types of
      genetic analyses, including genome mapping, genotype fingerprinting, phylogeny
      reconstruction, and measuring genetic similarities. They suffer from one
      potential limitation, however, because the PCR that is used to produce
      informative amplification products often produces artifactual products as well.
      Optimization of PCR protocols to eliminate artifactual bands completely is often
      too costly or too time-consuming to be practical. Other methods for handling RAPD
      artifacts, such as deleting inconsistent or faint bands or using only those bands
      that are reproducible, introduce false negatives into the data. Simply ignoring
      artifacts and using all bands introduces false positives. When RAPD data are used
      to compute genetic similarity coefficients, such artifacts can cause significant
      bias in the estimation. The three coefficients most widely used with RAPD data,
      the simple matching coefficient, Jaccard's coefficient and Nei and Li's
      coefficient, differ in the amount of bias produced by a given level of
      artifactual bands. The simple matching coefficient and Nei and Li's coefficient
      always exhibit less percent bias than Jaccard's coefficient. For closely related
      organisms, Nei and Li's coefficient displays less percent bias than the simple
      matching coefficient. If new DNA samples possessing RAPD markers not present in
      the previously analyzed samples are added to a study, values of the simple
      matching coefficient will need to be computed for all samples, not just the new
      ones. Jaccard's and Nei and Li's coefficients, however, will not need to be
      recomputed. Furthermore, only Nei and Li's coefficient has a direct biological
      meaning (it is an estimate of the expected proportion of amplified fragments
      shared by two samples because they were inherited from a common ancestor). On the
      basis of these results, Nei and Li's coefficient is recommended for routine
      computation of genetic similarities using RAPD data, particularly if PCR
      artifacts are present.

PMID- 9018315
TI  - Computing genetic similarity coefficients from RAPD data: correcting for the
      effects of PCR artifacts caused by variation in experimental conditions.
AB  - The production of informative random amplified polymorphic DNA (RAPD) markers
      using PCR and a single primer is often accompanied by the generation of
      artifactual (noninformative) bands as well. When RAPD data are used to compute
      genetic similarity coefficients, these artifacts (false positives, false
      negatives, or both) can cause large biases in the numerical values of the
      coefficients. As a result, some workers have been reluctant to use RAPD markers
      in the estimation of genetic similarities. Artifactual bands are of two types:
      those caused by variation in experimental conditions, and those caused by
      characteristics of the DNA to be amplified. A procedure is described that allows
      for correction of the bias caused by the first type of artifact, providing that
      replicate DNA samples have been extracted, amplified, and scored. The resulting
      data are used to obtain an estimate of the proportion of false-positive and false
      negatives bands. These values are then used to correct the bias in the computed
      similarity coefficients. Two examples are given, one in which bias correction is
      critical to the results, and one in which it is less important. The maximum
      percent bias, computed from the estimated proportions of false positives and
      false negatives in the RAPD data set, is proposed as a criterion for determining
      whether bias correction of the similarity coefficients is required or not.
      Although all reasonable efforts should be made to optimize PCR protocols to
      eliminate artifactual bands, when this is not possible, the methods described
      allow RAPD markers to compute genetic similarities reliably and accurately, even
      when artifactual bands resulting from variation in experimental conditions are
      present.

PMID- 9018316
TI  - PCR-based method to map the bending locus of DNA molecules.

PMID- 9018317
TI  - A simple PCR method for screening cDNA libraries.

PMID- 9018318
TI  - Comparison of gel matrices for resolving PCR-amplified DNA fingerprint profiles.

PMID- 9018319
TI  - A nonisotopic single-strand conformation polymorphism protocol using a direct
      blotting electrophoresis, a chemiluminescent detection system, and a multiplex
      approach.

PMID- 9018320
TI  - A DNA extraction method that allows reliable PCR amplification of MLO DNA from
      "difficult" plant host species.

PMID- 9018321
TI  - Buffer components tailor DNA amplification with arbitrary primers.

PMID- 9018323
TI  - Advanced methods in PCR product detection.

PMID- 9018322
TI  - Reverse transcriptase can inhibit PCR and stimulate primer-dimer formation.

PMID- 9018324
TI  - Strategies for direct sequencing of PCR-amplified DNA.

PMID- 9018325
TI  - Protocols for trapping internal and 3'-terminal exons.

PMID- 9018326
TI  - On beyond classic RACE (rapid amplification of cDNA ends).

PMID- 9018327
TI  - DNA fingerprinting by arbitrarily primed PCR.

PMID- 9018328
TI  - RNA fingerprinting by arbitrarily primed PCR.

PMID- 9018329
TI  - Neuroendocrine differentiation in carcinomas of the prostate: do neuroendocrine
      serum markers reflect immunohistochemical findings?
AB  - The aim of the present study was to examine the correlation between the
      immunohistochemical findings and the serum markers for neuroendocrine (NE) cells
      in patients with carcinoma of the prostate. Preoperative serum values of
      chromogranin A (CgA), chromogranin B (CgB), pancreastatin (Pst), neuron-specific
      enolase (NSE), and prostatic specific antigen (PSA) were determined in 22
      patients. The tissue specimens were obtained by a palliative transurethral
      resection of the prostate (TURP) because of urinary outflow obstruction.
      Immunohistochemistry was performed by using antibodies against CgA, CgB,
      NSE,.serotonin, thyroid-stimulating hormone (TSH), and somatostatin. Tumor cells
      with NE differentiation were found in 91% of the cases. No patient had elevated
      serum values of NSE, despite the presence of NSE-positive tumor cells in 77% of
      the tumors. Neither did CgB in serum correlate with the immunohistochemical
      findings. Elevated serum values of CgA were found in 59% of patients. A positive
      correlation between the number of CgA-staining cells and the serum values of CgA
      was found, as seven out of eight patients with groups of CgA-positive tumor cells
      had elevated serum values of CgA. We conclude that CgA, in contrast to NSE, CgB,
      and Pst, seems to be a useful serum marker in predicting the extent of NE
      differentiation in prostatic tumors.

PMID- 9018330
TI  - Extended culturing of androgen-responsive human primary epithelial prostate cell
      isolates by continuous treatment with interstitial collagenase.
AB  - Continuous culturing of two distinct human prostate specimens in the presence of
      interstitial collagenase added directly to conventional medium resulted in the
      isolation and extended growth of primary epithelial prostate cell (PEPC) cultures
      from each. Both continued to proliferate substantially beyond the average time
      determined for analogous untreated epithelial prostate isolates. Both repeatedly
      stain positive for keratin and are characteristically epithelial in morphological
      appearance and growth model. Both express androgen receptor mRNA and stain
      positive for androgen receptors. PEPC-2 displays an androgen dose-dependent
      stimulation of cell proliferation, as well as specifically binding 3H-R1881. PEPC
      1 exhibits a hypotetraploid karyotype with loss of the Y chromosome. PEPC-2
      conserves a normal human ploidy, including the Y chromosome, although there is
      extensive random chromosome loss. Elimination of the collagenase from the medium
      resulted in decreased cellular proliferation and accumulation of stainable
      collagen in both PEPC cultures. Neither PEPC isolate produced tumors in male nude
      mice, whether injected alone, mixed with matrigel, or combined with prostate or
      bone fibroblastic cells.

PMID- 9018331
TI  - PSA-based screening for prostate cancer in asymptomatic younger males: pilot
      study in blood donors.
AB  - BACKGROUND: The efficacy and success of a screening program for prostate cancer
      in young and healthy asymptomatic volunteers are described. METHODS: In the
      present study, prostate specific antigen (PSA) samples obtained from 2,272 males
      (aged 40-65 years) who donated blood at the local Red Cross Blood Bank were
      evaluated. Two groups of donors were distinguished, which were investigated in
      different ways. Group 1 comprised individuals aged 40-49 years (n = 568), while
      group 2 consisted of males aged 50-65 years (n = 1,704). Volunteers in group 2
      who had PSA levels greater than 4 ng/ml (n = 302) were referred for ultrasound
      guided biopsy irrespective of findings on digital rectal examination (DRE). In
      group 2, individuals with PSA levels exceeding 4 ng/ml and positive DRE findings
      biopsy specimen was ordered (n = 2). In patients with unremarkable findings on
      DRE, serum PSA was determined 1 year later and in case of more than 20% increase
      in the PSA level biopsy was obtained under ultrasound guidance. RESULTS: The
      biopsy specimen yielded prostatic carcinoma in 58 patients in group 1. As a
      screening test, serum PSA determination was superior to digital rectal
      examination. On digital palpation only 2 presented with abnormal prostates. These
      58 patients underwent radical prostatectomy and histological examination revealed
      organ-confined disease in all but 8. In group 2, in 4 of 12 males the biopsy
      specimen yielded prostatic carcinoma. CONCLUSIONS: This study shows that PSA
      measurement in blood donors is a useful method for recruiting screening
      volunteers, and therefore represents an additional possibility for early
      detection of prostate cancer in asymptomatic younger males. Furthermore, it
      represents an effective tool for following relatively young patients known to
      have a significant risk of prostate cancer.

PMID- 9018332
TI  - Prolactin and testosterone regulation of mitochondrial zinc in prostate
      epithelial cells.
AB  - The prostate gland of many animals accumulates extremely high levels of zinc and
      citrate. Evidence currently exists in support of a concept that zinc might be an
      important regulator of m-aconitase and citrate oxidation of prostate epithelial
      cells. No information concerning the mitochondrial levels of zinc has been
      available. The roles of testosterone and prolactin in the regulation of zinc have
      not been established. In this report, we determined the levels of tissue and
      mitochondrial zinc of rat lateral prostate (LP), ventral prostate (VP), dorsal
      prostate (DP), liver, and kidney. The results demonstrate that the mitochondrial
      zinc levels of the prostate cells were higher than levels of nonprostatic cells.
      The LP contained severalfold higher zinc levels than DP and VP. The effects of
      testosterone and prolactin in vivo and in vitro on the zinc levels were also
      determined. Both hormones significantly increased cellular and mitochondrial zinc
      levels of LP cells; decreased the zinc levels of VP cells; and had no effect on
      the zinc levels of DP, liver, or kidney cells. These effects are direct and
      physiological effects of the hormones on the targeted prostate epithelial cells.
      The hormonal effects on mitochondrial zinc of LP and VP epithelial cells
      correlate perfectly with their effects on citrate oxidation. The results support
      the concept that mitochondrial zinc is an inhibitor of m-aconitase and citrate
      oxidation; and that prolactin and testosterone regulation of mitochondrial zinc
      provides a mechanism for their regulation of citrate oxidation in citrate
      producing prostate epithelial cells.

PMID- 9018333
TI  - Ultrasound reflections fail to reflect the histopathology of the prostate.
AB  - High-resolution profiles of the reflections of a broad-band 4 MHz ultrasound
      pulse from radical prostatectomy and autopsy specimens in vitro have been
      captured and analyzed. An attempt was made to correlate the histopathology of
      each prostate reflection site with the profile of the pulse reflected from that
      site. Reflections from 125 sites on 22 prostate specimens were studied. Although
      the reflected pulse from each site displayed a distinctive profile, we could find
      no obvious correlation between the shape of that profile and the histologic
      findings at that site.

PMID- 9018334
TI  - Lipid composition in epithelium and stroma of human benign prostatic hyperplasia.
AB  - The lipid composition and concentration in human benign prostatic hyper-plasia
      (BPH) were investigated. The reason was to shed some light onto the lipid
      environment of cellular membranes, in which the epithelial and stromal 5 alpha
      reductase of the human prostate have apparently to be embedded in order to gain
      an active state. The phospholipids were found to be the major portion (67% +/-
      1.1) of total lipids in whole BPH homogenate, followed by cholesterol (29% +/-
      1.1) and glyceride glycerols (4% +/- 0.9). In BPH epithelium, the lipid
      concentration related to wet weight and to protein was two to three-fold higher
      than in stroma. Assigning the lipid concentration on a per-cell basis (i.e.,
      related to DNA), a significantly lower lipid concentration was found in the
      epithelium as compared to the stroma. In the stroma, a significantly higher
      phospholipid and lower cholesterol portion were found than in the epithelium.
      Moreover, sphingomyelin was found to comprise a higher portion in stromal than in
      epithelial phospholipids, whereas the percentage of phosphatidylserine was higher
      in the epithelial phospholipids. We discuss whether the significant differences
      in lipid concentration and composition between the epithelium and stroma of human
      BPH could have an impact on the activity of the membrane-bound 5 alpha-reductase,
      or whether such differences in the lipid environment are due to a different
      hormonal milieu in the epithelium and stroma of BPH.

PMID- 9018335
TI  - Coregulatory effects of epidermal growth factor, dihydrotestosterone, and
      prolactin on benign human prostatic hyperplasia tissue culture proliferation.
AB  - BACKGROUND: A variety of hormones have demonstrated effects on prostatic tissue
      growth dynamics. Our goal was to define the effect of dihydrotestosterone (DHT),
      epidermal growth factor (EGF), and prolactin (PRL) on prostate cellular
      proliferation. METHODS: Thirty benign human prostatic hyperplasias (BPH) were
      maintained 48 hr as in vitro cultures. Culture media were supplemented with EGF,
      DHT, and PRL alone and in combinations. Proliferation was assessed by labeling
      with tritiated thymidine. RESULTS: The proliferative response of individual BPH
      cultures was heterogeneous. DHT and EGF tended to have a greater proliferative
      effect than PRL, both in terms of the percent cultures responding and the
      magnitude of the response. PRL antagonized EGF-induced proliferative effects. EGF
      and PRL-mediated effects correlated with each other, while DHT-mediated effects
      did not correlate with either those of PRL or EGF. CONCLUSIONS: The proliferative
      response of individual BPH to DHT, EGF, and PRL, alone or in combination, is too
      variable to define a predictable response to their influence. Our methodology
      represents a technique with the capacity to define therapeutic potential for
      individual cases.

PMID- 9018336
TI  - Comparison of ras activation in prostate carcinoma in Japanese and American men.
AB  - BACKGROUND: Comparative studies of point mutations in K-, N-, and H-ras oncogenes
      were performed on prostate carcinoma from Japanese and American patients to
      clarify the racial difference. METHODS: We probed for mutations in 70 Japanese
      and 31 American specimens using polymerase chain reaction-single-strand
      conformation polymorphism (PCR-SSCP) analysis and immunohistochemistry for ras
      p21. RESULTS: Within the 70 Japanese specimens, eight mutations in codon 12 of K
      ras (five GGT-->GTT transversions and three CGT-->GAT transitions) and one
      mutation in codon 12 of the N-ras gene (a GGT-->GTT transversion) were confirmed,
      whereas the American samples yielded only one definable mutation, a GGT-->GAT
      transition, in codon 12 of K-ras. CONCLUSIONS: The frequency of ras gene
      mutations in clinical carcinoma in Japanese men was higher than that in American
      men. It is suggested that there may be fundamental differences in the etiology of
      prostate carcinoma in Japan and the United States, perhaps based on genetics
      and/or environmental factors.

PMID- 9018337
TI  - Immortalized and tumorigenic adult human prostatic epithelial cell lines:
      characteristics and applications Part 2. Tumorigenic cell lines.
AB  - This is Part 2 of a three-part review and deals with tumorigenic cell lines.
      Several immortalized and malignant adult human prostatic epithelial cell lines
      have been recently developed. The three most widely used carcinoma cell lines-DU
      145, PC-3, and LNCaP-developed between 1977 and 1980, have greatly contributed to
      our current understanding of prostate cancer. Before a cell line can be accepted
      as having prostatic epithelial origin, some basic characteristics must be
      established. Expression of specific cytokeratins but absence of desmin and factor
      VIII should be first determined to establish epithelial origin. Responsiveness to
      androgens and expression of androgen receptor and prostate-specific antigen
      should be examined under stringent culture conditions to establish prostatic
      epithelial origin. Response to growth factors and expression of their receptors
      facilitates further characterization of cell behavior. Cell lines immortalized by
      human papillomaviruses (HPVs) are of special interest because HPVs are involved
      in a variety of anogenital cancers and may also play a role in prostate
      carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the
      ras oncogene provides cell systems for investigating the multistep process of
      carcinogenesis. Each cell line has some unique characteristics, whether it arose
      directly from a carcinoma or resulted from immortalization with Simian virus 40
      (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these
      characteristics should facilitate elucidation of the mechanisms involved in the
      initiation, promotion, and progression of prostate cancer. These cell lines will
      further serve as useful models for investigating tumor progression, invasion,
      metastasis, new therapeutic strategies, drug resistance, and its reversal and
      chemoprevention. The nontumorigenic cell lines were discussed in Part 1 [1]. This
      review summarizes the characteristics of several currently available tumorigenic,
      adult human prostatic epithelial cell lines.

PMID- 9018338
TI  - Monoclonal antibody 7E11.C5 staining of viable LNCaP cells.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA) is a transmembrane
      glycoprotein defined by the monoclonal antibody 7E11.C5. The 7E11.C5 antibody
      forms the basis of an in vivo diagnostic imaging agent (ProstaScint, Cyt-356) for
      identification of metastatic prostate cancer. The epitope on PSMA recognized by
      7E11.C5 has been determined to be the first 6 amino acids from the N-terminal,
      expressed on the cytoplasmic side of the plasma membrane. Thus, the basis for
      7E11.C5 specificity in imaging studies remains unclear. METHODS: Fluorescence
      activated cell sorter (FACS) analysis of fixed and viable cultured cells was used
      to determine the staining intensity with FITC-labeled antibodies. RESULTS: The
      results indicate that FITC-labeled 7E11.C5 antibody is taken up and specifically
      labels viable LNCaP cells in vitro. Labeling intensity of viable cells after 2 hr
      of antibody incubation was similar to that of fixed cells. No labeling of cells
      that do not express PSMA was observed, nor was labeling observed with LNCaP cells
      treated with an isotype-matched irrelevant antibody. CONCLUSIONS: Uptake and
      labeling of PSMA by FITC-labeled 7E11.C5 in viable cells in vitro strongly
      suggest that this is a major basis for effectiveness of the 7E11.C5 antibody
      during in vivo imaging applications with 111In-labeled antibody (ProstaScint, Cyt
      356).

PMID- 9018339
TI  - Antimicrobial susceptibility testing in progress.

PMID- 9018340
TI  - Continued BVDV education needed.

PMID- 9018341
TI  - More thoughts on alternative and complementary veterinary medicine.

PMID- 9018342
TI  - More thoughts on alternative and complementary veterinary medicine.

PMID- 9018343
TI  - More thoughts on alternative and complementary veterinary medicine.

PMID- 9018344
TI  - Benefits of a national database for patient medical records.

PMID- 9018345
TI  - Professionalism in the next century.

PMID- 9018346
TI  - What is your diagnosis? Retrobulbar meningioma in a dog.

PMID- 9018347
TI  - Theriogenology question of the month. Excessive hemorrhaging from ovarian
      hematomas on both ovaries.

PMID- 9018348
TI  - Difficult dermatologic diagnosis. Cutaneous leishmaniasis in a dog.

PMID- 9018349
TI  - The law of veterinary liability and the human-animal bond.

PMID- 9018350
TI  - Professional income of US veterinarians in public or corporate employment, 1995.

PMID- 9018351
TI  - Legal rights of veterinarians under veterinary Good Samaritan statutes and equine
      liability statutes.

PMID- 9018352
TI  - Prevalence of rabies in bats in Michigan, 1981-1993.
AB  - OBJECTIVES: To analyze the species distribution of animals submitted to the
      Michigan Department of Public Health (MDPH) for rabies testing during 1993. To
      determine whether any of the 9 species of bats residing in Michigan carries a
      disproportionate rabies burden, and to determine whether bats contributed the
      most cases of confirmed rabies during 1981 through 1992. DESIGN: Epidemiologic
      study. PROCEDURE: Records of animals submitted to the MDPH for rabies testing
      during 1993, and between 1981 and 1992, were reviewed. Information regarding type
      of animal submitted, specific species if the animal was a bat, county from which
      the animal was obtained, the identity of the submitting individual, species of
      the animal exposed, month of the submission, and results of rabies testing was
      extracted from these records. RESULTS: During 1993, the MDPH received 2,045
      submissions for rabies testing. Seventeen rabid animals were identified: 1 cat, 1
      skunk, and 15 bats. Two hundred forty-six bats were submitted for testing.
      Eptesicus fuscus, the big brown bat, accounted for 97.2% (239) of bat submissions
      and was the only species of bat that had positive results of testing for rabies.
      Annual percentages of submitted bats found to be rabid ranged from 2.0 to 11.0%,
      with a 13-year mean of 6.2%. CONCLUSIONS: 100% of the confirmed cases of rabies
      in bats reported in Michigan in 1993 were associated with in E fuscus. During
      1981 through 1992, most of Michigan's confirmed cases of rabies in animals
      developed in bats.

PMID- 9018354
TI  - Prevalence and inheritance of and selection for hip dysplasia in seven breeds of
      dogs in Sweden and benefit: cost analysis of a screening and control program.
AB  - OBJECTIVE: To determine the prevalence and changes over time in the prevalence of
      hip dysplasia; to ascertain whether prevalence or severity of hip dysplasia was
      associated with sex of the dogs, age at which coxofemoral joint status was
      evaluated, or ancestral background; to determine the effects of selective
      breeding; and to conduct an economic evaluation of the hip dysplasia program
      operated by the Swedish Kennel Club. DESIGN: Analysis of radiographic evaluations
      of coxofemoral joint conformity. ANIMALS: 83,229 dogs from 7 breeds registered by
      the Swedish Kennel Club. PROCEDURE: All radiographs were scrutinized by a single
      radiologist (LA), and coxofemoral joint conformation was classified as normal or
      dysplastic, with the degree of dysplasia classified as 1,2,3, or 4. RESULTS:
      Decreasing prevalence of hip dysplasia corresponding to selection of breeding
      stock and high heritabilities was found. Sex differences were documented in 3 of
      the breeds. This was interpreted as breed differences in the distribution of
      genes related to hip dysplasia. Economic analyses showed that costs of screening
      and registration of coxofemoral joints was less than the value of dogs estimated
      to have been saved from moderate, severe, or very severe hip dysplasia in 6 of
      the breeds. CLINICAL IMPLICATIONS: Documented effects of age suggest that all
      dogs should be screened at the same age, rather than screening a few dogs at an
      older, more revealing age. In screening and control programs based on an open
      registry with access to family records, decreasing prevalence of hip dysplasia
      can be expected, and related to selection of breeding stock.

PMID- 9018355
TI  - Prevalence and inheritance of and selection for elbow arthrosis in Bernese
      mountain dogs and Rottweilers in Sweden and benefit: cost analysis of a screening
      and control program.
AB  - OBJECTIVE: To determine the prevalence and charges over time in the prevalence of
      elbow arthrosis in Bernese Mountain Dogs and Rottweilers, to ascertain whether
      prevalence or severity of elbow arthrosis was associated with sex of the dogs,
      age at the time of elbow joint examination, or ancestral background, to determine
      the effects of selective breeding, and to conduct an economic evaluation of the
      elbow arthrosis program operated by the Swedish Kennel Club. DESIGN: Analysis of
      radiographic evaluations of elbow joint conformity. ANIMALS: 4,515 dogs from 2
      breeds registered by the Swedish Kennel Club. PROCEDURE: All radiographs were
      scrutinized by a single radiologist (LA), and elbow joint conformation was
      classified as normal or arthrotic, with the degree of arthrosis classified as 1,
      2, or 3. RESULTS: Decreasing prevalence of elbow arthrosis corresponding to
      selection of breeding stock and high heritabilities was found. Sex differences
      were documented in both breeds, but with contradictory directions. This was
      interpreted as breed differences in the distribution of genes related to elbow
      arthrosis. Economic analyses showed that costs of screening and registration of
      elbow joints was less than the value of dogs estimated to have been saved from
      moderate and severe elbow arthrosis in both breeds. CLINICAL IMPLICATIONS:
      Documented effects of age suggest that all dogs should be screened at the same
      age, rather than screening a few dogs at an older, more revealing age. In
      screening and control programs based on an open registry with access to family
      records, decreasing prevalence of elbow arthrosis can be expected, and related to
      selection of breeding stock.

PMID- 9018356
TI  - Five-year longitudinal study on limited food consumption and development of
      osteoarthritis in coxofemoral joints of dogs.
AB  - OBJECTIVE: To examine the effects of limited food intake on frequency and
      severity of osteoarthritis in coxofemoral joints of labrador Retrievers. DESIGN:
      Dogs were paired according to gender and body weight, within each litter at 8
      weeks of age. One dog of each pair was fed ad libitum. The limit-fed pairmate was
      fed 75% of the amount eaten the previous day by the ad libitum-fed counterpart.
      ANIMALS: 48 Labrador Retrievers. PROCEDURE: All dogs received the same diet.
      Radiographic evaluation of coxofemoral joints for frequency and severity of
      osteoarthritis were made when dogs were 4 and 6 months and 1, 2, 3, and 5 years
      old. RESULTS: Radiographic evaluation for osteoarthritis indicated greater
      frequency and more severity of osteoarthritis in the ad libitum-fed group of
      dogs. CLINICAL IMPLICATIONS: Analysis of data suggested that limit feeding of
      dogs over a 5-year period minimizes development of osteoarthritis in the
      coxofemoral joints.

PMID- 9018357
TI  - Evaluation of a hypertonic saline-dextran solution for treatment of dogs with
      shock induced by gastric dilatation-volvulus.
AB  - OBJECTIVE: To test the hypothesis that small volumes of hypertonic saline-dextran
      (HSD) solution can be used to effectively resuscitate dogs in shock induced by
      gastric dilatation-volvulus (GDV), and, compared with administration of large
      volumes of lactated Ringer's solution (LRS), can be used to limit the overall
      volume of fluid needed for resuscitation. DESIGN: Prospective, clinical study.
      ANIMALS: 15 dogs with GDV-induced shock. PROCEDURE: Initially, HSD solution (5
      ml/kg of body weight) or LRS (60 to 90 ml/kg) was administered. All dogs then
      received a maintenance administration (20 ml/kg/h) of LRS. Cardiorespiratory,
      blood gas, and serum biochemical analyses were performed over a 4-hour period
      after initiation of treatment. RESULTS: Systolic arterial and central venous
      pressures and plasma volume increased more rapidly in dogs in the HSD + LRS
      group. The cumulative dose of fluids administered to dogs in the HSD + LRS group
      was significantly less than that administered to dogs in the LRS group. Serum
      sodium and chloride concentrations and osmolality increased significantly in dogs
      in the HSD + LRS group, but not in dogs in the LRS group. Ventricular arrhythmias
      were detected in both groups of dogs, but did not appear to be induced by either
      form of fluid therapy. CLINICAL IMPLICATIONS: Administration of HSD rapidly
      restored cardiorespiratory function and induced resuscitation equivalent to
      administration of large volumes of LRS. Use of HSD solutions to treat dogs in GDV
      induced shock may be more efficient than use of isotonic fluids. Administration
      of HSD solution was not associated with noticeable complications.

PMID- 9018358
TI  - Suspected ehrlichial infection in five cats from a household.
AB  - Ehrlichiosis is a poorly recognized condition of cats that may be associated with
      anemia, leukopenia, thrombocytopenia, or dysproteinemia. Affected cats may have
      indirect fluorescent antibody titers to Ehrlichia canis and E risticii. We
      reviewed the clinical evaluation and response to treatment of 5 cats in a
      household where ehrlichial disease was suspected as the cause of recurrent
      leukopenias and thrombocytopenias. All of the cats had E risticii indirect
      fluorescent antibody titers and western blot confirmation of antibodies to 4 of
      the 9 major antigens of E risticii. Response to doxycycline was monitored
      serologically and hematologically in each cat, and indicated that administration
      of doxycycline at a dosage of 10 mg/kg of body weight, PO, every 12 hours, for a
      minimum of 21 days is necessary for treatment of this condition.

PMID- 9018359
TI  - Pulmonary lobectomy in the management of pneumonia in dogs: 59 cases (1972-1994).
AB  - OBJECTIVE: To evaluate the risk and efficacy of pulmonary lobectomy in dogs with
      pneumonia. DESIGN: Retrospective study. ANIMALS: 59 dogs with pneumonia.
      PROCEDURE: Review of medical records and telephone conversations. RESULTS: 54.2%
      of dogs had resolution of pneumonia after lobectomy, 20.3% died in the
      perioperative period, and 25.4% survived the perioperative period but pneumonia
      did not resolve. Pneumonia was caused by bacteria (25 dogs), fungi (12), foreign
      bodies (8), parasites (1), viruses (1), and allergies (1). In 11 dogs, the
      etiologic agent was not isolated. Bacterial or fungal pneumonias were
      significantly less likely to resolve compared with foreign body pneumonia or when
      an etiologic agent was not isolated. Perioperative mortality rate increased
      significantly with an increase in number of pulmonary lobes removed.
      Complications during surgery significantly increased perioperative mortality
      rate. Surgical era (1972 to 1983 vs 1984 to 1994) was a significant predictor of
      mortality, with the odds of dying in the perioperative period being 11 times
      greater between 1972 to 1983. The odds of failure to resolve pneumonia was 3
      times greater during 1972 to 1983. CLINICAL IMPLICATIONS: Number of pulmonary
      lobes removed and complications during surgery significantly affect perioperative
      mortality rate. Identification of etiologic agents may help in predicting dogs
      likely to resolve pneumonia after surgery.

PMID- 9018360
TI  - Hypokalemia syndrome in dairy cows: 10 cases (1992-1996)
AB  - OBJECTIVE: To evaluate clinical findings in cows with recumbency associated with
      hypokalemia. DESIGN: Retrospective case series. ANIMALS: 10 adult dairy cows with
      weakness or recumbency and hypokalemia. PROCEDURE: Signalment, history, physical
      examination findings, results of diagnostic tests, and response to treatment were
      extracted from the medical record of each cow. RESULTS: 8 cows were recumbent on
      admission and 2 were profoundly weak. All cows had been given isoflupredone
      acetate as treatment for ketosis prior to admission. All were hypokalemic (serum
      potassium concentration, 1.4 to 2.3 mEq/L) with no other apparent cause for
      recumbency. Despite treatment with potassium, plasma potassium concentrations
      within the reference range were achieved in only 6 of the 9 cows treated. Two
      cows responded to treatment. Three cows died, 3 were euthanatized, 2 improved
      clinically and were discharged, 1 was discharged while still recumbent, and 1 was
      sent to slaughter prior to treatment. Histologic examination of muscle tissue
      from 2 cows revealed myonecrosis and vacuolation consistent with hypokalemic
      myopathy. CLINICAL IMPLICATIONS: Hypokalemia should be considered in the
      differential diagnosis for cows that are weak or recumbent, particularly after
      treatment for ketosis with isoflupredone acetate. Aggressive treatment with
      potassium salts administered orally is indicated.

PMID- 9018361
TI  - Use of xylazine, butorphanol, tiletamine-zolazepam, and isoflurane for induction
      and maintenance of anesthesia in ratites.
AB  - Anesthetic effects of xylazine, butorphanol, tiletamine-zolazepam, and isoflurane
      in ratites (9 emus, 3 rheas, 6 ostriches) were determined. Anesthetic treatments
      included 4 regimens: induction and maintenance of anesthesia with isoflurane,
      preanesthetic tranquilization with xylazine and butorphanol followed by induction
      and maintenance of anesthesia with isoflurane, induction of anesthesia with
      tiletamine-zolazepam and maintenance with isoflurane, and preanesthetic
      tranquilization with xylazine and butorphanol followed by induction of anesthesia
      with tiletamine-zolazepam and maintenance with isoflurane. None of the birds
      developed irreversible adverse effects, but 2 developed brady cardia (1 was
      treated with atropine and responded) and 2 others developed transient apnea.
      Intravenous administration of tiletamine-zolazepam produced rapid and smooth
      induction of anesthesia in adult ostriches.

PMID- 9018362
TI  - Estimated prevalence of injection-site sarcomas in cats during 1992.
AB  - OBJECTIVE: To obtain an estimate of the yearly prevalence of injection-site
      sarcomas in cats. DESIGN: Mail survey of members of the American Association of
      Feline Practitioners. PROCEDURE: A questionnaire was sent to 1,112 veterinarians.
      RESULTS: 235 responses were sufficiently complete for inclusion in the study.
      Overall, responding veterinarians reported 744,993 cat visits in 1992,
      representing 434,638 individual cats (1.7 visits/cat). The estimated overall
      prevalence of injection-site sarcomas during 1992 was 0.00021 cases/cat visit
      (2.1 cases/10,000 cat visits) or 0.00036 cases/cat (3.6 cases/10,000 cats).
      CLINICAL IMPLICATIONS: Results suggest that injection-site sarcomas were rare
      during 1992.

PMID- 9018363
TI  - Neonatal hearing screening programs in Europe: towards a consensus development
      conference.

PMID- 9018364
TI  - Otoacoustic emissions in preterm infants: indications for cochlear development?
AB  - A longitudinal study of click-evoked otoacoustic emissions (CEOAEs) in 19 ears of
      11 preterm infants--post-conceptional age (PCA): 30 to 39 weeks--resulted in a
      total of 90 CEOAE recordings. All but one of the 19 ears showed an increase of
      CEOAE amplitude at increasing PCA. The mean increase rate was 1.36 dB per week
      (dB/wk) for the left ears (n = 11, SD = 1.04 dB/wk), and 1.17 dB/wk for the right
      ears (n = 8, SD = 0,87 dB/wk). In six ears of three infants we were able to
      follow a total of 15 frequencies of spontaneous otoacoustic emissions (SOAEs).
      All of the monitored SOAE frequencies showed a positive shift in frequency with
      time, ranging from about 10 Hz/wk around 2000 Hz to about 50 Hz/wk around 5000
      Hz. This increase of CEOAE amplitude and SOAE frequency indicates that OAE
      properties are not fully developed in preterm infants. Although the influence of
      middle ear properties cannot be excluded or proved, the observed SOAE frequency
      shift suggests development of the fine structures in the cochlea itself.

PMID- 9018365
TI  - Electroencephalographic responses to briefly introduced interaural intensity
      differences.
AB  - The stimulation techniques so far described in the literature, for recording the
      long-latency electroencephalographic responses to changes in interaural intensity
      difference (IID), cannot be regarded as being specific for binaural mechanisms
      because any change in IID has inevitably a stimulating effect also on purely
      monaural mechanisms. However, by making use of the relatively long recovery
      characteristics of cortical responses we were able to design a novel IID
      stimulus, which did not evoke any significant potential when it was presented
      monotically or diotically, yet produced lateral sound image shifts and therefore
      evoked pronounced long-latency responses when presented dichotically. The shift
      responses recorded from five subjects mainly consisted of a negative-positive
      wave sequence at latencies around 110 ms and 200 ms, respectively. These vertex
      potentials, which were tested in this work receive no significant contribution
      from the monaural or binaural mechanisms sensitive to overall sound intensity,
      should be useful as a diagnostic tool for assessing the level of maturation or
      the integrity of the sound lateralization mechanism based on IIDs.

PMID- 9018366
TI  - Alternobaric and hyperbaric oxygen therapy in the immediate and long-term
      treatment of Meniere's disease.
AB  - Forty-five patients suffering from Meniere's disease were submitted to pressure
      chamber therapy: 20 with constant pressure (2.2 ATA, hyperbaric treatment) and 25
      with continuous variations in pressure levels (from 1.7 to 2.2 ATA, alternobaric
      treatment). Oxygenation therapy consisted of one session per day lasting 90
      minutes for 15 days during the acute attacks followed by five consecutive
      sessions per month during a follow-up of two years. For a control group we used
      18 patients treated with 10 per cent intravenous glycerol during the acute
      episode and 8 mg tid of betahistine thereafter. We compared hearing loss, vertigo
      and tinnitus in the three groups 15 days after starting treatment and at the end
      of the follow-up, according to the criteria suggested by the 1995 Committee on
      Hearing and Equilibrium. We found no statistically significant differences in
      recovery from the cochlear-vestibular symptoms in the three groups at the end of
      the first 15 days of therapy, whereas hyperbaric and, in particular, alternobaric
      treatment permitted a significant control of the principal attacks of vertigo
      during the follow-up period. Hearing loss also showed a more significant and more
      persistent improvement in the patients treated with alternobaric oxygenation
      compared to the patients in the other two groups.

PMID- 9018367
TI  - Comparison of response properties of neurons in the inferior colliculus of guinea
      pigs under different anesthetics.
AB  - Responses of the inferior colliculus (IC) neurons to acoustical stimulation were
      recorded in anesthetized guinea pigs. Three kinds of anesthesia were used: (1)
      urethane (8 ml/kg b.w. of 20 per cent solution i.p.); (2) ketamine-xylazine
      combination (1 ml/kg b.w. of mixture 2:1); and (3) pentobarbital (25 mg/kg i.p.)
      combined with intramuscular injection of fentanyl (0.5 ml) and droperidol (1 ml).
      The frequency tuning of neurons evaluated on the basis of Q10 values and the
      composite neural audiogram represented by points of lowest thresholds of
      individual IC neurons were similar for guinea pigs treated with any of the
      anesthetics. The number of spontaneously active IC neurons was significantly
      larger with ketamine than with urethane or pentobarbital. The response latencies
      to tone bursts at characteristic frequency (CF) were shortest in animals
      anesthetized with pentobarbital. Whereas with ketamine and urethane many neurons
      were recorded in which response latencies were longer than 40 ms, in
      pentobarbital-anesthetized animals the latencies usually did not exceed 25 ms.
      The occurrence of neurons with an onset type of response was significantly larger
      with pentobarbital than with the other two anesthetics. In ketamine and urethane
      anesthesia, thresholds of units with sustained response were significantly lower
      than thresholds of units with onset response. Our results suggest that in
      experiments where the level of spontaneous activity, latency and type of
      responses were important parameters, the kind of anesthesia should be taken into
      account.

PMID- 9018368
TI  - Of mice and women: the beta 3-adrenergic receptor leptin and obesity.
AB  - The metabolic response of adipose tissue to stimuli leading to lipid mobilization
      is important in determining the direction of metabolism and the degree to which
      adipose tissue can store lipids and release fatty acids in times of need. The
      lipolytic machinery is controlled by the activity of hormone-sensitive lipase,
      which in turn is controlled by the cellular levels of cAMP. The production of
      cAMP is abnormal in the adipose tissue of some animal models of obesity. In the
      ob/ob mouse, the defective cAMP production has been associated with deficient
      levels of some of the isoforms of the guanine nucleotide transducing G-proteins
      and also with the low expression and functionality of the beta 3-adrenergic
      receptor (beta 3-AR). The recent discovery of the ob gene product leptin calls
      into question the role of the ob gene in the regulation of the cAMP cascade in
      adipose tissue. The importance of the beta 3-AR and leptin in regulating human
      adipose tissue metabolism remains to be clarified.

PMID- 9018369
TI  - Chromatin structure and function: the heretical path to an RNA transcription
      factor.
AB  - This review represents a synthesis of the work of the author and her
      collaborators through 40 years of research aimed at an understanding of chromatin
      composition and functional arrangement. It describes the progressive experimental
      stages, starting with autoradiography and protein analysis and continuing on to a
      more functional approach testing the template properties of intact nuclei, as
      well as nuclei depleted of, or reconstituted with, defined fractions extracted
      from the chromatin of other cell lines or tissues. As new questions were raised
      at each phase of these studies, the investigation was shifted from chromosomal
      proteins to the role of a small RNA that coextracted with one protein fraction
      and whose properties suggested a transcription-activating function. The active
      RNA was identified as a class III RNA, designated as 7SK. Its properties
      suggested a role in the activation of two oncogenes, the SV40 T-antigen and the
      mammalian C-myc gene. A detailed analysis of the c-myc gene expression during
      transformation induction in temperature-sensitive mammalian cells finally
      culminated in in vivo evidence for a role of 7SK in c-myc deregulation, using
      cells transfected with antisense oligonucleotides to block 7SK activity. This was
      followed by an investigation of promoter targeting by 7SK RNP using
      electrophoretic mobility shift assays with whole or 7SK-depleted cell extracts.
      Taken together, these studies indicate that 7SK RNP participates in
      transformation-dependent deregulation of the c-myc gene by activation of two c
      myc minor promoters. The implications of these findings are discussed.

PMID- 9018370
TI  - Spermidine-condensed DNA and cone-shaped lipids improve delivery and expression
      of exogenous DNA transfer by liposomes.
AB  - A new liposome system containing spermidine-condensed DNA and negative cone
      forming lipids designed to improve gene delivery and expression is described. The
      compacted nature of condensed DNA forms permitted a higher extent of
      encapsulation of DNA in liposomes. These vesicles contained fusogenic cone-shaped
      lipids to increase fusion between liposomes and membranes to enhance the amount
      of DNA delivery into the cells. In addition, the insensitivity of condensed DNA
      forms to endonucleases and restriction enzymes, as well as their higher activity
      in both replication and transcription, improve foreign DNA expression. These
      improvements in condensed DNA encapsulation in liposomes, transfer into the
      cells, and DNA expression increase the number of transfected cells and produce a
      higher level of gene expression in most transfected cells. This is reflected in
      the 60-fold cell culture transfection increase compared with traditional liposome
      transfection systems. This liposome system does not cause any apparent damage to
      the transfected cells; furthermore, the liposomes are small, 400-500 nm, and have
      negative surface charges that can prolong their circulation half-lives in vivo,
      permitting their use for in vivo gene therapy applications.

PMID- 9018371
TI  - Influence of testosterone on chondroitin sulphate proteoglycan in the rat
      prostate.
AB  - There are recognized interactions between prostatic stromal and epithelial cells.
      These interactions may be influenced by the composition of the extracellular
      matrix, which is composed of proteins such as collagen, laminin, fibronectin, and
      proteoglycans (PGs) such as chondroitin sulphate proteoglycan (CSPG). In our
      continuing studies on prostate biology, we examined the three lobes of the normal
      adult rat prostate, i.e., ventral, dorsal, and lateral, for CSPG by indirect
      immunofluorescence, using an immunospecific monoclonal antibody (CS-56) for the
      chondroitin sulphate (CS) moiety of the PG. Staining of the prostate sections
      with CS-56 antibody followed by labelling with IgG fluorescein isothiocyanate
      conjugate indicated strong fluorescent signals associated with the ventral lobe
      basement membrane. The signal was stronger and more continuous in the distal
      acini than in the proximal acini. The staining of the dorsal and lateral lobes
      was less intense than that of the ventral lobe. Following castration of the rats,
      the basement membrane staining became discontinuous. Androgen replacement by
      administration of testosterone propionate (TP) reversed the effects of
      castration. Quantification of the total CS content showed decreases of about 60%
      in the ventral and lateral lobes after castration. TP administration for 14 days
      increased the total CS content several fold above the values for castrated rats
      in all lobes. The results demonstrated that CS content was significantly higher
      for TP-treated animals, suggesting that the expression of prostate CSPG is
      regulated by androgens. This approach should be useful in the study of the
      extracellular matrix in prostate biology.

PMID- 9018372
TI  - Glycosaminoglycans in the three lobes of the rat prostate following castration
      and testosterone treatment.
AB  - Androgen dependence of glycosaminoglycans (GAGs) in the prostate was studied
      using tissue from intact (sham control), castrated, and androgen-treated
      castrated rats. GAGs from the ventral, dorsal, and lateral lobes of the prostate
      were isolated and characterized by cellulose electrophoresis using appropriate
      GAG standards and enzymatic digestion or nitrous acid hydrolysis. Androgen
      deprivation was initiated by castration and rats were sacrificed at various time
      intervals after 7 days castration. After castration, the total GAG content
      decreased in three prostate lobes. At day 7 after castration, the total
      hyaluronic acid (HA) content decreased by 74% (ventral lobe) and 34% (lateral
      lobe) compared with the sham control. No effect was observed for HA content in
      the dorsal lobe. Castration decreased the total heparan sulphate (HS), dermatan
      sulphate (DS), and chondroitin sulphate (CS) contents in the three prostate lobes
      at 0 days of treatment, except for the CS content in the dorsal and lateral
      lobes. Androgen replacement increased the total GAG contents in the three
      prostate lobes. At 14 days of testosterone propionate treatment, there were 9-,
      6.8-, 4.1- and 3.7-fold increases in HA, HS, DS, and CS, respectively, in the
      ventral lobe. These increases were more rapid and profound in the ventral than in
      the dorsal and lateral lobes. These findings indicate that all GAGs are regulated
      by androgen and there may be lobe-specific differences in their regulation. This
      could be a function of the heterogeneous populations of cells in each lobe.

PMID- 9018373
TI  - Production of type IV collagen and 72-kDa gelatinase by human endothelial cells
      cultured in high glucose. Effects of a protein kinase C inhibitor, GF 109203X.
AB  - Since diabetic microangiopathy and macroangiopathy are characterized by type IV
      collagen accumulation in vascular basement membranes, it was of interest to study
      type IV collagen production and type IV collagenase secretion by endothelial
      cells (EC) cultured in high glucose and to evaluate the role of protein kinase C
      (PKC) activation in the alterations induced by high glucose. Primary cultures of
      human umbilical vein EC were exposed to high glucose concentration for 3 days at
      the beginning of confluence. The number of EC decreased with glucose
      concentration from 5 to 50 mM. At 16.7 mM glucose concentration, the amount of
      type IV collagen, determined by a two-step ELISA, increased in the culture
      supernatant and in the insoluble fraction associated with the extracellular
      matrix and cells; proline incorporation was more markedly elevated in the
      collagenous than in the total proteins of the culture supernatant and of the
      extracellular matrix and cell extracts. Gelatin zymography of the culture
      supernatant showed that EC mainly produce a 72-kDa gelatinase known to degrade
      type IV collagen. At 16.7 mM glucose concentration, total gelatinase activity per
      millilitre of culture supernatant was reduced and the 72-kDa gelatinase activity
      measured on the zymogram scan was lowered. When EC were exposed to 16.7 mM
      glucose, the specific PKC inhibitor GF 109203X corrected the increases in type IV
      collagen concentration and in proline incorporation into the collagenous or total
      proteins present in he culture supernatant or in the extract of the insoluble
      fraction, including the extracellular matrix and cells. Our results show that
      soluble and insoluble type IV collagen accumulation by EC cultured at high
      glucose concentration is not only associated with increased synthesis of the
      collagenous and total proteins but also with decreased total 72-kDa gelatinase
      activity in the extracellular fluid. The observed effects of GF 109203X are in
      favor of the involvement of PKC activation in the type IV collagen accumulation.

PMID- 9018374
TI  - Cyclic AMP phosphodiesterase: a regulator of forward motility initiation during
      epididymal sperm maturation.
AB  - The concentrations of cAMP, cAMP phosphodiesterase (PDE) activity, and the effect
      of theophylline in vitro on the forward motility (FM) of maturing goat epididymal
      sperm have been analyzed. cAMP levels increase slowly during transit of the cells
      from the caput to the proximal cauda, although they acquired a minimal degree of
      forward progression. The last phase of sperm transit (proximal to distal cauda)
      was associated with a concomitant sharp rise in the level of both cAMP as well as
      flagellar motility. PDE activity progressively decreased (approximately
      threefold) during epididymal maturation, being minimal in mature cauda sperm.
      Theophylline (30 mM), a specific inhibitor of PDE, markedly activated (10-fold or
      greater) motility of the sperm derived from proximal-corpus, mid-corpus, distal
      corpus, and proximal-cauda epididymides. FM of the native mature caudal sperm was
      similar to that of the theophylline-treated proximal-cauda sperm. The terminal
      stage of sperm maturity (proximal to distal cauda) was associated with a markedly
      reduced level of theophylline-dependent motility activation (approximately 50%).
      The data are consistent with the view that PDE plays an important role in the
      initiation of motility during epididymal sperm maturation.

PMID- 9018375
TI  - Presence of two new fatty acid binding proteins in catfish liver.
AB  - A basic fatty acid binding protein (FABP), closely related to that of chicken
      liver, was isolated and characterized from catfish (Rhamdia sapo) liver in a
      previous work. Results herein show the presence of another two FABPs in which
      partial amino acid sequences reveal great similarity with the corresponding
      sequences of other already known FABPs belonging to the heart type. The
      purification procedures for both proteins involve gel filtration, anion-exchange
      chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (as
      a last step). Because both FABP N-termini were blocked, they were submitted to in
      gel tryptic digestion and the resulting peptides were separated by high
      performance liquid chromatography, and sequenced by Edman degradation. One of
      these proteins presented the highest identity percentage when compared with those
      of the human and bovine heart and bovine brain (81%), and the other when compared
      with those of chicken retina (75%) and mouse and bovine heart FABP (70%). The
      presence of several FABPs plus the fact that they belong to different types, as
      found in the Rhamdia sapo liver, is unusual in mammals, which express a
      characteristic liver-type member of this protein family.

PMID- 9018376
TI  - Transfer of cholesterol between high density lipoproteins and cultured rat
      Sertoli cells.
AB  - In the testes, the Sertoli cells are separated from the blood capillaries by the
      basement membrane, thereby excluding the passage of low density lipoproteins
      (LDLs) but allowing the passage of high density lipoproteins (HDLs). The present
      study examines first the capacity of Sertoli cells to uptake cholesterol from HDL
      and secondly the role of apolipoproteins (apo) A-I and E in cholesterol flux
      between HDL and cultured rat Sertoli cells. In the presence of HDL in cultured
      medium, rat Sertoli cells accumulated few amounts of esterified cholesterol.
      Incubation of [14C] cholesterol-labelled Sertoli cells with [3H]cholesterol
      labelled HDL showed that the amount of cholesterol influx slightly exceeded its
      efflux, thus resulting in a net uptake of cholesterol from HDL to rat Sertoli
      cells. The amount of HDL-cholesterol converted to steroids by Sertoli cells was
      about 32% of influx. Uptake of cholesterol by Sertoli cells was three times
      higher with phospholipid-apo A-I vesicles and seven times higher with
      phospholipid- apo E vesicles than that with phospholipid vesicles without
      apolipoprotein. Phospholipid- apo A-I vesicles promoted cholesterol efflux at the
      same rate as native HDL and twice as efficiently as phospholipid- apo E vesicles.
      Thus, this study shows that rat Sertoli cells have the capacity to take up HDL
      cholesterol for membrane renewal and steroid production mainly by apo E dependent
      pathways.

PMID- 9018377
TI  - Characterization of the Ca2+-binding properties of calgizzarin (S100C) isolated
      from chicken gizzard smooth muscle.
AB  - Calgizzarin is a Ca2+-binding protein of the S100 family that has been implicated
      in the regulation of cytoskeletal function through its Ca2+-dependent interaction
      with annexin I. The Ca2+-binding properties of calgizzarin (S100C) have not
      previously been thoroughly characterized. Calgizzarin, therefore, was purified
      from chicken gizzard smooth muscle by exploiting its Ca2+-dependent interaction
      with the hydrophobic matrix phenyl-Sepharose and is shown by 45Ca2+ overlay to
      bind Ca2+ more weakly than does calmodulin. Gel filtration in the absence and
      presence of Ca2+ suggested a dimeric structure of calgizzarin and indicated a
      more compact structure in the presence of Ca2+. Flow dialysis experiments
      indicated that, at physiological ionic strength, calgizzarin binds two Ca2+ ions
      per monomer (four per native dimer), as predicted from the deduced amino acid
      sequence which contains two putative EF-hands, with [Ca2+]0.5 of 0.52 mM and nH
      of 1.4 in the absence of Mg2+ and [Ca2+]0.5 of 0.3 mM and nH of 1.2 in the
      presence of 10 mM mgCl2. The hydrophobic fluorescent probe 2-p
      toluidinylnaphthalene-6-sulphonate was used to demonstrate Ca(2+)-dependent
      exposure of a hydrophobic site(s) in calgizzarin. This approach also indicated
      the ability of calgizzarin to bind Zn2+. Interestingly, the affinity of
      calgizzarin for Ca2+ was enhanced approximately 10-fold in the presence of the
      hydrophobic probe, possibly reflecting an increased affinity for Ca2+ when
      calgizzarin binds to a target protein. Finally, the distribution of calgizzarin
      among chicken tissues was examined by immunoblotting: calgizzarin was expressed
      at its highest levels in lung tissue, followed by smooth muscle tissues
      (oesophagus, large intestine, trachea, and gizzard), kidney, liver, brain, and
      heart; it was not detected in small intestine or skeletal muscle.

PMID- 9018378
TI  - Purification and partial characterization of bovine kidney aldehyde dehydrogenase
      able to oxidize retinal to retinoic acid.
AB  - A NAD-dependent enzyme that catalyzes the oxidation of retinal to retinoic acid
      has been purified to homogeneity from bovine kidney. The procedures used in the
      purification included ion-exchange chromatography on DEAE-Sepharose, affinity
      chromatography on Affi-gel blue and chromatography on a Mono-Q anion-exchange
      column. On the Mono-Q column, the enzyme aldehyde dehydrogenase (ALDH) resolved
      into two activity peaks designated as ALDH1 and ALDH2. The enzymes ALDH1 and
      ALDH2 were purified about 114- and 65-fold, respectively. Gel filtration
      chromatography of the partially purified native enzyme on Sephacryl S-200 HR
      exhibited a molecular mass of about 108 kDa. Electrophoresis of the purified
      enzymes under nondenaturing conditions showed a single protein band. However,
      sodium dodecyl sulfate--polyacrylamide gel electrophorsis indicated three protein
      bands in the 55, 30, and 22 kDa molecular mass regions. Both enzymes exhibited a
      broad substrate specificity oxidizing a wide variety of aliphatic and aromatic
      aldehydes. The ALDH1 enzyme had a pI of 7.45 and exhibited a low Km (6.37 microM)
      for retinal, while the ALDH2 enzyme was found to have very low Km for
      acetaldehyde (0.98 microM). Based on its kinetic properties, it is suggested that
      the ALDH1 enzyme may be the primary enzyme for oxidizing retinal to retinoic acid
      in bovine kidney.

PMID- 9018379
TI  - Modulation of the cleavage of glycosylphosphatidylinositol-anchored proteins by
      specific bacterial phospholipases.
AB  - Many enzymes are tethered to the extracellular face of the plasma membrane by a
      glycosylphosphatidylinositol (GPI) anchor. These proteins can be released in
      soluble form by the action of GPI-specific phospholipase. Little is currently
      known about the factors modulating this release. We investigated the effects of
      several experimental variables on the cleavage of the GPI-anchored proteins
      5'nucleotidase, acetylcholinesterase, and alkaline phosphatase by phospholipases
      from Bacillus thuringiensis and Staphylococcus aureus. Phospholipase activity was
      not inhibited by isotonic salt and was relatively unaffected by buffer type and
      concentration. In both cases, the optimum pH for cleavage was approximately 6.5.
      Over 80% of 5'-nucleotidase activity present in the lymphocyte plasma membrane
      was cleaved by the B. thuringiensis enzyme, and the initial rate of release was
      linear with phospholipase concentration. All three GPI-anchored proteins were
      released from lymphocyte plasma membrane at comparable phospholipase
      concentrations, suggesting that they have similar anchor structures. The
      catalytic activity of 5'-nucleotidase appeared to increase following conversion
      to the soluble form. The relative surface charge of the host plasma membrane
      modulated catalytic activity towards GPI-anchored proteins, depending on the net
      charge of the phospholipase. Studies on purified lymphocyte 5'-nucleotidase
      reconstituted into bilayers of dimyristoylphosphatidylcholine indicated that the
      efficiency of phospholipase cleavage was 12- to 50-fold lower when compared with
      the native plasma membrane. The ability of the phospholipase to cleave the GPI
      anchor was further reduced when the bilayer was in the gel phase.

PMID- 9018380
TI  - Heterogeneity of myosin heavy-chain expression in fast-twitch fiber types of
      mature avian pectoralis muscle.
AB  - The aims of this study are to investigate the diversity of myosin heavy-chain
      (MyHC) expression among avian fast-twitch fibers, and to test the hypothesis that
      dissimilar MyHC isoforms are found in each of the principal avian fast-twitch
      fiber types. MyHCs within the muscle fibers of the pectoralis of 31 species of
      bird are characterized using immunocytochemical methods. A library of 11
      monoclonal antibodies previously produced against chicken MyHCs is used. The
      specificity of these antibodies for MyHCs in each of the muscles studied is
      confirmed by Western blots. The results show that avian fast-twitch glycolytic
      fibers and fast-twitch oxidative-glycolytic fibers can contain different MyHCs.
      Among the species studied, there is also a conspicuous variety of MyHC isoforms
      expressed. In addition, the results suggest that two epitopes are restricted to
      chickens and closely allied gallinaceous birds. There are no apparent
      correlations between between MyHC epitope and presupposed contractile properties.
      However, the presence of different isoforms in different fast-twitch fiber types
      suggests a correlation between isoform and contractile function.

PMID- 9018381
TI  - Neuroscience: where is it heading? Some reflections on the future of brain
      research at the end of the second millenium.

PMID- 9018382
TI  - Guanine nucleotide binding proteins in opioid-dependent patients.
AB  - Guanine nucleotide binding (G) protein levels and functioning in the platelets of
      19 methadone-maintained patients were compared to age and sex matched, normal
      controls. We found that in the methadone patients, G alpha s-levels were
      significantly higher, while the levels of G alpha i 1/2 and pertussis toxin
      catalyzed [32P]ADP ribosylation were significantly lower compared to control
      subjects in platelet membranes. We have further found that when all three of
      these biochemical indicators were combined in a discriminant function analysis,
      79% of the methadone patients were correctly classified and 83% of the controls
      were correctly classified.

PMID- 9018383
TI  - Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for
      neuroprotective pharmacotherapy.
AB  - The development of neuroprotective agents for the prevention of neuronal loss in
      acute conditions such as stroke and epilepsy or chronic neurodegenerative
      disorders including Parkinson's disease, Alzheimer's disease, Huntington's
      chorea, and motor neuron disease is currently focusing on drugs that inhibit
      excitatory amino acid neurotransmission or exhibit antioxidant properties.
      Unfortunately, potent antagonists at the N-methyl-D-aspartate (NMDA) type
      glutamate receptor, which is thought to mediate excitotoxic neuronal injury,
      e.g., MK-801 or phencyclidine (PCP), share a high probability of inducing
      psychotomimetic side effects. Further, these drugs have been associated with
      acute neurotoxicity in vitro and in vivo, precluding their clinical use. In
      contrast, low affinity NMDA receptor antagonists like amantadine and its dimethyl
      derivative, memantine, have been administered clinically for the management of
      Parkinson's disease, dementia, neuroleptic drug-induced side effects, and
      spasticity. These agents have only rarely induced significant psychotomimetic
      side effects. Recent pharmacologic advances have helped to elucidate how high
      drug affinity for the PCP binding site of the NMDA receptor may enhance
      psychotogenicity. Low affinity and associated fast voltage-dependent channel
      unblocking kinetics are likely to be responsible for the better tolerance of
      amantadine and memantine compared with MK-801 and PCP. Further factors apparently
      modulating psychotogenicity of glutamate receptor antagonists include
      differential actions on neuronal populations in various brain regions and
      interactions with neurotransmitter receptors other than the NMDA type glutamate
      receptor.

PMID- 9018384
TI  - Relationships between hormonal profile and novelty seeking in combat-related
      posttraumatic stress disorder.
AB  - This study examines relationships between hormonal levels and novelty seeking in
      a group of 27 Vietnam veterans with combat-related posttraumatic stress disorder
      (PTSD). Novelty seeking in the veteran sample, measured by the Cloninger
      Tridimensional Personality Questionnaire (TPQ), was almost twice as high as
      previously published norms. A distinctive pattern of significant positive
      correlations was found between novelty seeking scores and serum total
      triiodothyronine (T3), free T3, the T3/free thyroxine (FT4) ratio, urinary
      norepinephrine and the norepinephrine/cortisol ratio, while a negative
      correlation was found between novelty seeking scores and urinary cortisol levels.
      The findings were confirmed by t test analyses of high vs low novelty seeking
      subgroups and do not appear to be related simply to the severity of PTSD. These
      preliminary findings indicate the need to include measures of characterological
      traits in psychoendocrine studies of PTSD and to investigate their possible
      usefulness in subtyping this disorder.

PMID- 9018385
TI  - I-123 iofetamine single-photon computed emission tomography in rapid cycling
      bipolar disorder: a clinical study.
AB  - The regional distribution of I-123 iofetamine (IMP) in the brain of 12 patients
      with rapid cycling bipolar disorder was studied by single-photon computed
      emission tomography imaging. Patients who were either medication free (n = 4) or
      on lithium monotherapy (n = 8) were assessed serially in depressed/dysphoric,
      manic/hypomanic, or euthymic states. In 23 imaging studies, IMP images of the
      brain were taken on a GE Starcam system 20 min after injection of 3-4 mCi of I
      123 labeled IMP. The I-123 IMP distribution in the anterior part of the temporal
      lobes was asymmetric in both depression/dysphoria and mania/hypomania but not in
      euthymia. Images taken sequentially on the same patient showed temporal lobe
      asymmetry in the pathological mood states that diminished or disappeared in the
      euthymic state. The observed changes most likely reflect an altered cerebral
      blood flow and changes in high-affinity IMP binding to amine receptors in the
      temporal lobes. This pilot study suggests the presence of a state-dependent
      temporal dysfunction in bipolar disorder.

PMID- 9018386
TI  - Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed
      inpatients.
AB  - Previous studies have found that not all suicide attempters with major depression
      have reduced serotonergic activity based on low cerebrospinal fluid 5
      hydroxyindoleacetic acid (CSF- 5-HIAA) levels. In this study we hypothesized that
      serotonergic function is lower in depressed patients who have carried out high
      lethality suicide attempts resulting in more medical damage, which might explain
      differences in serotonergic activity among depressed suicide attempters. We
      assessed the relationship of CSF 5-HIAA and other amine metabolites to the most
      lethal lifetime suicide attempt in 22 drug-free inpatients with major depression.
      CSF 5-HIAA levels were lower in depressed patients with a history of a high
      lethality or well-planned suicide attempt compared to depressed patients with a
      history of only low-lethality suicide attempt(s). Other CSF monoamine metabolites
      did not correlate with suicidal behavior. Low serotonergic activity may correlate
      with a predisposition to more lethal suicide attempts in major depression.

PMID- 9018387
TI  - Serotonin transporter expression in rat brain regions and blood platelets: aging
      and glucocorticoid effects.
AB  - Hyperactivity of the hypothalamus-pituitary-adrenal axis is more common in
      elderly depression than in younger cohorts and glucocorticoids are known to
      influence serotonergic systems. The current study explores the interaction of
      glucocorticoids with aging on serotonin transporter expression and function.
      Continuous infusions of dexamethasone (26 days) reduced transporter expression in
      the aged brain but the ability of imipramine to inhibit synaptosomal
      [3H]serotonin uptake was unimpaired. These effects were unique to aged animals,
      as prior work with young adults found no effects of dexamethasone on transporter
      expression. In contrast to the effects in the brain, there were no differences in
      platelet transporter expression between young and old rats nor did dexamethasone
      treatment affect the values in the aged group: thus, the platelet may not
      reliably model these aspects of CNS function. The results suggest that there are
      basic biologic differences in the effects of glucocorticoids in aged vs. young
      brain that could contribute to lowered effectiveness to antidepressants in
      elderly depression; if transport capacity is already reduced by the effects of
      increased glucocorticoids, further inhibition of transport by antidepressants
      would have proportionally less impact on synaptic serotonin concentrations.

PMID- 9018389
TI  - The effect of apolipoprotein E genotype on expression of an autosomal dominant
      schizophreniform disorder with progressive dementia and neurofibrillary tangles.
AB  - The apolipoprotein E (APOE) epsilon 4 allele is associated with an increased and
      the epsilon 2 allele a decreased risk for Alzheimer's disease (AD). It has been
      hypothesized that these risks are mediated by differential effects of the APOE
      alleles on the cytoskeletal degeneration, which results in neurofibrillary tangle
      (NFT) formation. It has also been suggested that APOE alleles differentially
      affect the beta amyloid accumulation. We examined APOE genotypes and their
      effects on age of onset in a family with an autosomal dominant "neurofibrillary
      tangle only" dementia. This disorder is manifested by schizophreniform psychosis
      followed by progressive dementia and neuropathologically by prominent AD-like
      neurofibrillary tangles without neuritic plaques. The only affected epsilon 4
      heterozygote in this family did not demonstrate accelerated disease onset. In
      contrast, the affected epsilon 2 heterozygote had the latest age of onset of any
      affected family member. The two other epsilon 2 heterozygotes remained unaffected
      at an age much greater than the mean age of onset for the disease. These results
      are consistent with a protective effect of the epsilon 2 allele in a hereditary
      neuropsychiatric disorder with prominent NFT formation.

PMID- 9018388
TI  - Effects of selective serotonin reuptake inhibitors on platelet serotonin
      parameters in major depressive disorder.
AB  - The effects of treatment with serotonin (5-HT) reuptake inhibitors on platelet 5
      HT2 receptors, 5-HT reuptake sites an 5-HT uptake were studied in a double-blind
      trial comparing two selective serotonin reuptake inhibitors (SSRI), paroxetine,
      and fluoxetine, for the treatment of major depression. Hamilton Depression Rating
      Scale (HAM-D) scores and platelet 5-HT parameters were determined in 21 depressed
      patients at baseline, after 4 and 8 weeks of treatment, and were compared to 21
      healthy controls. Antidepressant treatment did not significantly alter the
      density of 5-HT reuptake sites, labelled with [3H]paroxetine, or 5-HT2 receptors,
      labelled with [3H]LSD. However, a strong correlation was observed between the HAM
      D suicidality item and 5-HT2 receptor density at baseline. A marked increase in
      platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients
      compared to those with no suicidal ideation and healthy controls. Changes in
      [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change
      in HAM-D score at 4 and 8 weeks respectively. These results confirm previous
      reports of an association between suicidality and platelet 5-HT2 receptor
      upregulation. Our data also lends support to the use of platelet 5-HT parameters
      as indicators of antidepressant efficacy, particularly in suicidal depressed
      patients.

PMID- 9018390
TI  - Low serum cholesterol in suicide attempters.
AB  - Previous studies have shown an association between low serum cholesterol
      concentration and suicide; however, conflicting results have also been reported.
      To examine this potential association, cholesterol levels in 99 patients admitted
      to an emergency ward following an attempted suicide were compared with those in
      74 nonsuicidal psychiatric inpatients, and those in 39 psychiatrically normal
      individuals with accidental injuries. Cholesterol concentrations in suicide
      attempters were found to be significantly lower compared with both psychiatric
      and normal controls, when sex, age, psychiatric diagnosis, and physical
      conditions (serum total protein and red blood cell count) were adjusted for. This
      significant relationship was observed in mood disorders and personality or
      neurotic disorders, but not in schizophrenia spectrum disorders. These results
      support the previous claim that lower cholesterol level is associated with an
      increased risk of suicidal behavior.

PMID- 9018391
TI  - Auditory event-related potentials in mentally retarded subjects during active and
      passive oddball experiments.
AB  - Auditory event-related potentials were recorded from subjects performing an
      active and/or a passive oddball task. The subjects belonged to three groups: 27
      nonretarded (NR) subjects; 39 "discriminating" retarded (DR) subjects; and 12
      "nondiscriminating" retarded (NDR) subjects. With respect to NR subjects, DR
      subjects had significantly longer latencies for peaks N1, P2, N2 and P3 in the
      active task and for N2 in the passive task, and NDR subjects had significantly
      longer latencies for peaks N2 and P3 in the passive task. We conclude: that the
      generation of P3 may involve both a permanent automatic basis and controlled
      processes whose intervention depends on the attention paid to the P3-inducing
      stimuli; and that whether a mentally retarded subject exhibits significantly
      lengthened P3 latency in a particular task depends on the degree to which the
      cognitive processes involved in performance of that task are affected by the
      causes of his or her retardation.

PMID- 9018392
TI  - Subjective and psychophysiologic insomnia: an examination of sleep tendency and
      personality.
AB  - The goal of this study was to compare insomniacs with and without objective
      verification, on the basis of sleep parameters, personality, and performance. An
      insomniac complaint group was subclassified as objective insomniac (OI) or
      subjective insomniac (SI) and compared to a non-complaint group. Groups did not
      differ on night sleep variables or daytime sleep latency measures; rather, a
      consistent sleep tendency was revealed for all three groups. The poorer the
      previous night sleep, the longer the daytime sleep latencies. Groups differed on
      subjective measures of conscious state during the day. SIs inaccurately estimated
      sleep/wake state in comparison to objective measures on the MSLT, whereas OIs
      were accurate in their estimations. Personality scores showed trends that
      suggested greater neuroticism for SIs and introversion for OIs. Results
      demonstrated subjective tendencies and related personality types that may help in
      the understanding of the complaint of insomnia with and without objective
      findings.

PMID- 9018393
TI  - Electroencephalographic abnormalities in patients with presenile dementia of the
      Alzheimer type: quantitative analysis at rest and during photic stimulation.
AB  - In the present study, quantitative electroencephalographic (EEG) analysis was
      performed at rest and during photic stimulation (5, 10, and 15 Hz) in nine
      patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 55
      years) and nine sex- and age-matched control subjects. Compared with the normal
      controls, the AD patients had a significantly lower alpha-2 and beta band power
      in the resting EEG as well as a significant increase in delta and theta band
      power. EEG analysis during the photic stimulation demonstrated that the AD
      patients had a significantly lower EEG power during photic stimulation for the
      alpha (9.8-10.2 Hz) and beta bands (14.8-15.2 Hz) corresponding to photic
      stimulation at 10 Hz and 15 Hz, respectively. In addition, when we examined EEG
      changes from rest to the stimulus condition, the AD patients were found to show
      significantly smaller changes in EEG power mainly over the posterior regions,
      irrespective of the stimulus frequency. These findings provide evidence that AD
      patients have EEG abnormalities in both non-stimulus and stimulus conditions, and
      suggest diminished EEG reactivity to photic stimulation.

PMID- 9018394
TI  - Consideration of the relevance of ethological animal models for human repetitive
      behavioral spectrum disorders.
AB  - Treatment successes of various stereotyped behaviors in animals and humans has
      renewed interest in ethologic animal models for the study of psychiatric
      disorders. This report presents another such behavior occurring in horses to
      weaving. This anomalous, repetitive, and purposeless behavior draws analogies to
      human compulsive spectrum behaviors. A "weaver" provided an opportunity to
      evaluate serotonin, dopamine, and opioid neurotransmitter system contributions by
      probing each with a selective agent in A-B-A-C-A-D design. The horse was treated
      in sequential 1-month periods separated by 1-month washouts with a serotonin
      transport inhibitor (SRI), opiate antagonist (OA), and neuroleptic (DA).
      Videotape was taken weekly and analyzed by two blind raters. Frequency of head
      swings, latency to onset, and severity were recorded. The SRI showed > 95%
      symptom reduction, the DA 40%, and OA 30%. The findings suggest that
      neurochemical explanations of disturbance based on single drug vs. placebo trials
      may be oversimplified. Multiple-system probes are needed to dissect complex
      interactive biological systems. Animal model research can have an important role
      in such investigations.

PMID- 9018395
TI  - Disturbances of one-carbon metabolism in neuropsychiatric disorders: a review.

PMID- 9018396
TI  - The Pisa syndrome (pleurothotonus) during antidepressant therapy.

PMID- 9018397
TI  - Alterations of peak distribution of auditory ERPs during transient global
      amnesia: a case report.

PMID- 9018398
TI  - Sertraline and akathisia: spontaneous resolution.

PMID- 9018399
TI  - Exclusion of linkage of schizophrenia to the gene for the glutamate GluR5
      receptor.

PMID- 9018400
TI  - No association between apolipoprotein E genotype and late-onset depression in
      Alzheimer's disease.

PMID- 9018401
TI  - Cardiovascular, respiratory, and panic reactions to epinephrine in panic disorder
      patients.

PMID- 9018402
TI  - Longitudinal study of blue cone retinal function in cocaine-withdrawn patients.

PMID- 9018403
TI  - A review of effects of hypothyroidism on vascular transport in skeletal muscle
      during exercise.
AB  - Hypothyroidism is a common thyroid disease characterized by exercise intolerance.
      Both exercise capacity and endurance are compromised in the hypothyroid state.
      Studies involving rats performing treadmill running have shown that blood flows
      during exercise to high oxidative, extensor-type muscles are lower in hypothyroid
      rats compared with those in euthyroid rats. Abnormal cardiac and vascular
      function appear to contribute to this hypoperfusion. Experiments involving
      isolated arterial vessel segments have demonstrated that potential for
      constriction is normal in vessels from hypothyroid animals; however, reduced
      vasodilator potential is associated with hypothyroidism. Dysfunction of both
      endothelium and vascular smooth muscle appear to contribute to blunted potential
      for vasodilation. Altered ability to generate vasodilatory substances and/or
      changes in responses to these vasodilators may account for vascular dysfunction.
      It appears that impaired vascular function interacts with other factors such as
      poor myocardial function and changes in energy metabolism to compromise exercise
      tolerance.

PMID- 9018404
TI  - A new measurement of tissue capillarity: the capillary-to-fibre perimeter
      exchange index.
AB  - The surface area of contact between capillaries and muscle fibres has been
      suggested to be the site of greatest oxygen flux density in the movement of
      oxygen from the capillaries to the muscle fibres. A new measurement of tissue
      capillarity, designed specifically for use on non-perfusion fixed muscle tissue
      (i.e., that obtained via needle biopsy), is presented that describes the
      capillary supply from this perspective. The Capillary-to-Fibre Perimeter Exchange
      Index (the CFPE Index) is derived as the quotient of the individual capillary-to
      fibre ratio (i.e., the capillary-to-fibre ratio calculated for each fibre
      individually) and the fibre perimeter. This method is suggested to provide a
      means of quantitating potential alterations in the capacity for oxygen flux
      (e.g., as may occur in response to a training intervention) and any carrier- or
      receptor-mediated aspect of blood-tissue exchange between the capillaries and
      muscle-fibres (e.g., insulin or glucose delivery).

PMID- 9018405
TI  - The ventilatory response to hypoxia below the carbon dioxide threshold.
AB  - The ventilatory response to acute progressive hypoxia below the carbon dioxide
      threshold using rebreathing was investigated. Nine subjects rebreathed after 5
      min of hyperventilation to lower carbon dioxide stores. The rebreathing bag
      initially contained enough carbon dioxide to equilibrate alveolar and arterial
      partial pressures of carbon dioxide to the lowered mixed venous partial pressure
      (approximately equal to 30 mmHg), and enough oxygen to establish a chosen end
      tidal partial pressure (50-70 mmHg), within one circulation time. During
      rebreathing, end-tidal partial pressure of carbon dioxide increased while end
      tidal partial pressure of oxygen fell. Ventilation increased linearly with end
      tidal carbon dioxide above a mean end-tidal partial pressure threshold of 39 +/-
      2.7 mmHg. Below this peripheral-chemoreflex threshold, ventilation did not
      increase, despite a progressive fall in end-tidal oxygen partial pressure to a
      mean of 37 +/- 4.1 mmHg. In conclusion, hypoxia does not stimulate ventilation
      when carbon dioxide is below its peripheral-chemoreflex threshold.

PMID- 9018406
TI  - Effects of 5-day exercise training in elderly subjects on resting left
      ventricular diastolic function and VO2max.
AB  - We evaluated the effects of short-term, high-intensity exercise training and
      detraining on resting left ventricular diastolic function (LVDF) and maximal
      aerobic power (VO2max) in 7 sedentary older (age = 68 +/- 4 years) men (n = 5)
      and women (n = 2). Training consisted of cycling for 60 min with power output set
      at 70% (Day 1), 80% (Day 2), and 90% (Days 3-5) of the pretraining peak work
      rate. Detraining consisted of a return to regular exercise habits. LVDF increased
      10% in the early (E) flow velocity, decreased 18% in the late (A) flow velocity
      wave, and decreased 31% in the isovolumic relaxation time. VO2max was increased
      12% while plasma volume (PV) increased 10% following training and returned to
      baseline after detraining. The exercise-induced change in VO2max was directly
      related to the change in E/A (r = .52) and indirectly related to the change in
      IVRT (r = -.62). It was concluded that short-term, high-intensity exercise
      training improves LVDF and is tolerated well in older subjects, and that the
      calculated changes in PV and aerobic power are similar to those observed
      previously in a younger population.

PMID- 9018407
TI  - A comparison of three fluid replacement strategies for maintaining euhydration
      during prolonged exercise.
AB  - The effectiveness of a new water delivery system (the Water-Del) was examined for
      maintaining euhydration compared to other fluid replacement strategies. Subjects
      (N = 10) performed three 60-min cycling trials (/50% of VO2max) in an
      environmental chamber (27 degrees C; RH = 50%). Trials were randomly assigned
      from Water-Del (metered: 200 ml water every 15 min), ad libitum every 15 min (ad
      lib-15), and ad libitum (ad-lib). Total water intake (TWI), changes in plasma
      volume (delta PV), body weight (delta BW), thirst, skin temperature (Tsk), and
      heart rate (HR) were measured. A significant difference (p < or = .05) among
      trials was observed for TWI, with metered (1,200 +/- 0 ml) being greater than ad
      lib-15 (358 +/- 48 ml) and ad-lib (522 +/- 106 ml). No significant difference was
      found for delta PV. A significant difference (p < or = .05) for delta BW was
      observed with metered (0.28 +/- 0.16 kg) being different than ad-lib-15 (-0.63 +/
      0.12 kg) and ad-lib (-0.34 +/- 0.14 kg). No significant differences (p > .05)
      were found for thirst, Tsk, or HR. The water-Del provides for greater fluid
      intake during exercise compared to other replacement strategies.

PMID- 9018408
TI  - Frequent serum sampling in healthy men discloses testosterone peaks exacerbated
      by testosterone propionate administration.
AB  - Interval samplings uncover blood diurnal oscillations for several hormones,
      highlighting the importance of short time intervals in the disclosure of subtle
      pulsatile patterns of some peptide hormones, namely LH. In a study designed to
      develop new probes against steroid misuse, venous blood was sampled at 5-min
      intervals for 4 hours from 12 eugonadal adult male athletes, 6 receiving
      transcutaneous administrations of testosterone propionate and 6 placebo subjects.
      Brief supraphysiologic serum testosterone peaks were disclosed, the amplitude and
      frequency of these peaks being larger for the treated group. No solid explanation
      could be given to explain these bursts. Neither the binding/dissociation kinetics
      of SHBG molecules with and without increased circulating level of
      dihydrotestosterone, nor brief testosterone-inducing LH bursts, nor increased
      Leydig cell release could be invoked to explain these peaks. Their occurrence,
      although relatively rare, could represent a threat and lead to improper
      treatment.

PMID- 9018409
TI  - Serum lipid levels and steroidal hormones in women runners with irregular menses.
AB  - This study compared the lipid profile of women runners with menstrual cycle
      irregularities with their normally menstruating counterparts. Relationships among
      selected steroid hormones and serum lipid levels in 10 eumenorrheic (EU) and 8
      oligo-/amenorrheic (O/A) women runners and 6 eumenorrheic controls (CON) were
      examined. Serum 17 beta-estradiol (E2), progesterone (Prog), and
      dehydroepiandrosterone-sulfate (DHEAS) concentrations were determined in daily
      blood samples for 21 days, and integrated concentrations were calculated. Fasting
      blood samples were analyzed for total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL2, HDL3,
      triglycerides (Trig), and apolipoproteins A-1, A-II, and B. The O/A group had
      significantly lower E2 and Prog than EU or CON groups. Women in the CON group had
      lower HDL-C and HDL3 than the runners. With all women grouped together, E2 was
      not significantly correlated with any measured blood lipid parameters. On the
      other hand, DHEAS was significantly correlated with HDL-C, HDL2, and
      apolipoprotein A-I. These data demonstrate that women runners, regardless of
      menstrual cycle status, exhibit higher HDL-C concentrations than CON and supports
      previous research reporting a positive association between DHEAS and HDL-C.

PMID- 9018410
TI  - Relationship between aerobic fitness and metabolic recovery from intermittent
      exercise in endurance athletes .
AB  - This investigation examined the relationship between several different aerobic
      fitness test results and measurements of metabolic recovery from intermittent,
      high-intensity exercise in 16 male cyclists. No significant correlations were
      found between maximal oxygen consumption, ventilation threshold, various
      submaximal endurance measures and the rate of metabolic recovery, net excess
      postexercise oxygen consumption, or blood lactate removal after intermittent high
      intensity exercise except for submaximal heart rate (r = .66, p < .05). These
      data indicate that aerobic fitness assessments do not indicate the ability to
      recover after intermittent, high-intensity exercise in endurance-trained
      cyclists.

PMID- 9018411
TI  - Spondyloepimetaphyseal dysplasia and abnormal dentition in siblings: a new
      autosomal recessive syndrome.
AB  - The clinical and radiological features are described in male and female siblings
      with a unique form of spondyloepimetaphyseal dysplasia. In addition to
      generalized platyspondyly with epiphyseal and metaphyseal involvement, these
      children also have thin tapering fingers with accentuated palmar creases and
      abnormal dentition with oligodontia and pointed incisors. Parental consanguinity
      suggests that this is an autosomal recessive disorder.

PMID- 9018412
TI  - New syndrome: brain malformation, growth retardation, hypokinesia and
      polyhydramnios in two brothers.
AB  - We report two brothers who were born after pregnancies characterized by
      polyhydramnios and hypokinesia. Both had brain malformation (absence of corpus
      callosum in one; arhinencephaly in the other), telecanthus and narrow palpebral
      fissures. This family and several similar phenotypes reported only in affected
      brothers could reflect X-linked inheritance.

PMID- 9018413
TI  - A new form of mandibulofacial dysostosis with macroblepharon and macrostomia.
AB  - We report on a girl aged 7 years with normal mental development but an unusual
      form of mandibulofacial dysostosis. The hallmarks of the syndrome are a round,
      flat face, severe hypertelorism, downslanting palpebral fissures extending to the
      temples, a broad nasal base, anteverted nares, small, posteriorly rotated ears, a
      long, smooth philtrum, a thin upper lip, striking macrostomia, retrognathism with
      reduced height of the mandible, and irregularly placed teeth, some to them
      missing.

PMID- 9018414
TI  - Cranio-oculo-fronto-nasal malformation: a new MCA condition?
AB  - We describe a boy born to non-consanguineous parents who presents a singular
      clinical picture characterized by severe mental retardation, craniosynostosis,
      ocular abnormalities, and frontonasal malformation. This seems to be a previously
      undescribed condition of unknown aetiology which should be mainly distinguished
      from craniofrontonasal dysplasia, and frontofacionasal dysostosis.

PMID- 9018415
TI  - Unusual type of brachydactyly associated with intraventricular septal defect and
      deafness: a new condition?
AB  - We report a patient with brachydactyly associated with an intraventricular septal
      defect and sensorineural deafness. The second fingers had ulnar curvature.
      Radiographs showed bilateral hypoplastic middle phalanges of the 2nd and 5th
      fingers and the left 2nd digit showed hyperphalangy. The association of this
      unusual brachydactyly, intraventricular septal defect, and deafness does not
      conform to any known condition.

PMID- 9018416
TI  - Congenital emphysema, cryptorchidism, penoscrotal web, deafness, and mental
      retardation--a new syndrome?
AB  - The clinical features of an 8-year-old boy with congenital emphysema,
      cryptorchidism, a penoscrotal web, deafness, constipation and mental retardation
      are described. Review of the literature did not reveal another report of this
      unusual combination of features.

PMID- 9018417
TI  - New syndrome or severe expression of Gordon syndrome? A case report.
AB  - A boy with multiple congenital anomalies including median cleft palate, bilateral
      hearing loss, clino- and camptodactyly, bilateral single palmar flexion creases,
      severe hypotonia with kyphoscoliosis and respiratory insufficiency, failure to
      thrive, bilateral cryptorchidism and facial dysmorphism (epicanthus, a flat nasal
      bridge, a small mouth, a small nose with anteverted nostrils, low-set ears, a
      prominent forehead, microretrognathia) is presented. His mother has a median
      cleft palate, bilateral hearing loss, single palmar flexion creases, and short
      stature. An autosomal or X-linked dominant syndrome with more severe expression
      in the proband than in his mother is suggested.

PMID- 9018418
TI  - Identical twins with the classical form of Schwartz-Jampel syndrome.
AB  - The Schwartz-Jampel syndrome is a rare disorder inherited as an autosomal
      recessive trait. The main clinical features of this syndrome include generalized
      myotonic myopathy, skeletal dysplasia, blepharophimosis, microstomia, contracture
      of joints and short stature. This report concerns a pair of female monozygotic
      twins with Schwartz-Jampel syndrome. Minor physical differences were found in the
      toes and joints affected. Additionally, both showed severe microcephaly and
      previously undescribed X-ray manifestations: a small skull, disproportion between
      skull and facial structures and dysharmonic bone maturation. This is the first
      report of identical twins with this syndrome.

PMID- 9018419
TI  - Gerodermia osteodysplastica in a Bedouin sibship: further delineation of the
      syndrome.
AB  - We report a Bedouin family with gerodermia osteodysplastica in which there are
      two affected female siblings. They have a prematurely aged face with loose and
      wrinkled skin, joint laxity/dislocation, and osteoporosis. Unusual traits that
      have not been previously reported in association with gerodermia osteodysplastica
      were ear anomalies and an abnormal EEG.

PMID- 9018420
TI  - Antley-Bixler syndrome: case report and review of the literature.
AB  - The purpose of this report is to describe a patient with a pattern of
      malformations very similar to those described by Antley and Bixler. They include
      craniosynostosis, midface hypoplasia with proptosis, ear anomalies, choanal
      stenosis, long tapered fingers with a bulbous tip, elbow joint contracture due to
      radio-ulnar synostosis and talipes equinovarus. Necropsy revealed cardiac and
      renal malformations. The infant died a few days after birth, of respiratory
      failure. Unlike previously described cases the elbow joint contracture was due to
      radio-ulnar synostosis rather than radio-humeral synostosis, she did not have
      long bone fractures and the femora were not markedly bowed. Since the first
      report in 1975, at least 23 cases have been reported.

PMID- 9018422
TI  - Sirenomelia, limb reduction defects, cardiovascular malformation, renal agenesis
      in an infant born to a diabetic mother.
AB  - The clinical features of a fetus with sirenomelia, limb reduction defects,
      cardiovascular malformation and renal agenesis are reported. The mother of the
      child suffers from insulin dependent diabetes. The limb, cardiac and renal
      abnormalities are well recognized sequelae of diabetic pregnancies. The
      association of sirenomelia and maternal diabetes is somewhat controversial. The
      link between caudal regression syndrome, sirenomelia and maternal diabetes will
      be discussed.

PMID- 9018421
TI  - Phenotypic diversity in the Smith-Lemli-Opitz syndrome.
AB  - The phenotype of four cases of Smith-Lemli-Opitz syndrome (SLO) with proven
      defects in cholesterol biosynthesis are compared, and shown to be markedly
      disparate even between sibs, and demonstrate the dilemma for the clinician. The
      advent of a biochemical test for SLO has been enormously valuable in determining
      which patients are truly affected by the condition, but because of the wide
      phenotypic variation, a diagnosis on clinical features alone remains problematic.

PMID- 9018423
TI  - Tetraamelia associated with a syrinx: fortuitous association or clue?
AB  - We report a male infant born at 43 weeks of gestation with tetraamelia. The upper
      limbs consisted of the presence of very short stumps containing a single bone.
      The lower limbs were totally absent. There were also a facial hemangioma, mild
      micrognathia, testis ectopia and osseous malformations. A magnetic resonance
      imaging exam showed no significant abnormality of the brain but disclosed a
      cervico-dorso-lumbar syringomyelic cord without any other associated spinal
      malformation. Teratogenic as well as genetic causes are discussed.

PMID- 9018424
TI  - Bonneau syndrome: a further case report.

PMID- 9018425
TI  - Prenatal diagnosis of cloverleaf skull in the subtype 2 Pfeiffer syndrome.

PMID- 9018426
TI  - How common is precocious puberty in patients with Williams syndrome?

PMID- 9018427
TI  - Follow-up report on the 'Poland anomaly/primary microcephaly association'.

PMID- 9018428
TI  - Angiographic abnormalities of experimental autoimmune uveoretinitis.
AB  - PURPOSE: Experimental autoimmune uveoretinitis (EAU) is an invaluable animal
      model for studying inflammatory eye disease in humans. Indocyanine green (ICG) is
      a fluorescent dye that can be used to image both retinal and choroidal vessels.
      This study was performed to examined the retinal and choroidal vascular
      abnormalities of a rat model of EAU using ICG and fluorescein as the contrast
      media to assess the suitability of this model for studying ICG angiographic
      abnormalities in inflammatory eye disease in humans. METHODS: Twenty-six black
      hooded Lister rats were inoculated with bovine retinal S-antigen plus adjuvant
      with or without Bordetella pertussis antigen. Fluorescein and ICG angiograms were
      performed at different stages of clinical disease with a scanning laser
      ophthalmoscope. RESULTS: EAU was more severe and primarily choroidal disease in
      rats given Bordetella pertussis, but no animals showed evidence of dye leakage
      from large choroidal vessels. There was frank leakage of indocyanine green from
      retinal vessels. Leakage of both fluorescein and ICG retinal vessels largely
      correlated with disease activity. Retinal pigment epithelial lesions either
      corresponded to areas of hypofluorescence on the ICG angiogram alone or were
      represented by areas of ICG hyperfluorescence that had overlying areas of
      fluorescein leakage from retinal capillaries. CONCLUSIONS: This study has
      demonstrated the vascular abnormalities of this model of EAU using ICG and
      fluorescein as the contrast media. The suitability of this method for studying
      ICG angiographic abnormalities in inflammatory eye disease in humans is
      encouraging.

PMID- 9018429
TI  - Human vitreous hyaluronidase: isolation and characterization.
AB  - PURPOSE: Hyaluronic acid (HA) is the predominant glycosaminoglycan (GAG) of the
      human vitreous. Interaction of this HA with vitreous collagen is important for
      maintaining gel structure. The mechanism of HA homeostasis in the vitreous is
      incompletely understood. The aim of this study was to determine whether
      hyaluronidase, an endoglycosidase that degrades HA, was present in human
      vitreous. METHODS: Vitreous samples were collected from post-mortem eye bank
      specimens and from non-hemorrhagic, non-inflamed biopsy specimens. Vitreous
      hyaluronidase was purified by a series of column chromatographic steps, and its
      activity was measured by an ELISA-like assay and by substrate gel electrophoresis
      through and HA-impregnated gel. The purified hyaluronidase was also analyzed by
      SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and by Western blotting.
      RESULTS: Hyaluronidase activity was detected in vitreous samples from both post
      mortem and biopsy specimens. The enzyme was most active at acid pH, but
      demonstrated significant activity at neutral pH. The partially purified enzyme
      migrated as a 59 kDa protein on SDS-PAGE, and a single band on Western blots.
      CONCLUSIONS: Hyaluronidase is present in the human vitreous. Thus, hyaluronidase
      may be involved in HA catabolism in the vitreous and may play a role in
      determining its gel structure.

PMID- 9018430
TI  - A primary culture model of rabbit conjunctival epithelial cells exhibiting tight
      barrier properties.
AB  - PURPOSE: The present study was conducted to develop and characterize a functional
      primary culture of pigmented rabbit conjunctival epithelial cells on permeable
      support exhibiting tight barrier properties. METHODS: Conjunctival epithelial
      cells were isolated by 0.2% protease treatment, cultured at 0.5-1.8 x 10(6)
      cells/cm2 onto collagen-treated Transwell filters, and were maintained either in
      the presence of 1% fetal bovine serum throughout or serum-free media from day 3
      onwards. Transepithelial potential difference (PD) and transepithelial electrical
      resistance (TEER) were measured and equivalent short-circuit current (Ieq =
      PD/TEER) estimated. RESULTS: There appears to be a critical plating density of
      1.5 x 10(6) cells/cm2 for functional development of tight epithelial cell
      cultures. The culture conditions as noted above did not affect either the time
      when peak bioelectric parameters were attained (days 8-10) or the magnitude of
      these parameters at a plating density of 1.5 x 10(6) cells/cm2. Specifically,
      cells grown in a serum-free media showed a peak TEER of 1.9 +/- 0.2 k omega.cm2,
      a PD of 14.2 +/- 1.6 V (apical side negative), and and Ieq of 8.0 +/- 0.4
      microA/cm2 (mean +/- SEM, n = 45). Electron microscopy of serum-weaned cultures
      revealed a multilayered epithelium with numerous microvilli on the outermost
      layer of cells, while sporadic positive Periodic Acid Schiff (PAS) staining under
      light microscopy suggested the presence of mucin-secretory goblet cells.
      CONCLUSIONS: A functional, tight, epithelial barrier of the pigmented rabbit
      conjunctiva on a permeable support has been developed, which may be useful for
      mechanistic studies of ion and drug transport at the cellular level.

PMID- 9018431
TI  - Permeability characteristics of primary cultured rabbit conjunctival epithelial
      cells to low molecular weight drugs.
AB  - PURPOSE: To evaluate the permeability characteristics of primary cultured rabbit
      conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of
      varying lipophilicity. METHODS: 3H-mannitol; hydrophilic sotalol and atenolol;
      moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic
      betaxolol were used as model compounds. RESULTS: The conjunctival apparent
      permeability coefficient (Papp) of mannitol (1 x 10(-7) cm/s) was 2.4 times lower
      than that of the most hydrophilic beta-blocker, sotalol (Papp = 2.4 x 10(-7)
      cm/s). Differences in the degree of tightness of the epithelial cell layers
      brought about a 30-fold difference in the transport of atenolol in favor of the
      leaky cell layers, while not affecting the transport of the lipophilic drug,
      propranolol. Within the log partition coefficient (PC) range of -0.62 (sotalol)
      and 3.44 (betaxolol), there was a hundred-fold difference in the Papp. A
      sigmoidal curve was used to depict the influence of lipophilicity on solute
      permeation across conjunctival epithelial cell layers. An effective half-maximal
      Papp was observed at a log PC value of 1.2. CONCLUSIONS: These findings on the
      lipophilicity effect on drug transport are generally similar to those reported
      for the isolated rabbit conjunctiva, suggesting the utility of cultured rabbit
      conjunctival epithelial cell layers as an in vitro model for evaluating drug
      transport.

PMID- 9018432
TI  - Detection of different metabolites in the rabbit lens by high resolution 1H NMR
      spectroscopy.
AB  - PURPOSE: To investigate the metabolic profile of the rabbit lens using high
      resolution 1H NMR spectroscopy including two-dimensional shift correlated (COSY)
      technique. METHODS: Perchloric acid extracts of the rabbit lens were analysed
      with a Bruker AM-500 spectrometer and the metabolites were assigned in the
      spectra. Some of these were also quantified. RESULTS: More than 20 metabolites
      were detected in the perchloric acid extract of a single lens, including amino
      acids, nucleotides and other related compounds. Of particular importance is the
      ability to detect and identify glutathione, myoinositol, scyllo-inositol and
      taurine. CONCLUSIONS: The study demonstrated the potential of 1H NMR spectroscopy
      for monitoring the metabolic profile of the lens in normal and pathologic
      conditions.

PMID- 9018433
TI  - Pantethine inhibits the formation of high-Tc protein aggregates in gamma B
      crystallin solutions.
AB  - PURPOSE: Solutions of the bovine lens protein gamma B (or gamma II) crystallin at
      neutral pH in the absence of reducing agents, undergo a slow, partial conversion
      to a new protein species, gamma IIH. This species is an aggregate composed of an
      intermolecular, disulfide-crosslinked dimer (approximately equal to 32% of total
      protein by weight) and loosely associated dimers (approximately equal to 66%).
      gamma IIH has a phase separation temperature (Tph), at least 40 degrees C higher
      than that of native gamma II crystallin at any given protein concentration. In
      this paper we demonstrate that pantethine, a derivative of coenzyme A, inhibits
      the formation of gamma IIH. METHODS: gamma II crystallin solutions were incubated
      at pH 7.1 and room temperature with increasing amounts of pantethine. The Tph of
      the solutions was monitored as a function of incubation time. Corresponding to
      each Tph measurement, aliquots of each solution were analyzed by cation-exchange
      HPLC to determine the amount of gamma IIH formed. RESULTS: Incubation of gamma II
      crystallin with increasing amounts of pantethine lowers Tph and suppresses the
      formation of gamma IIH. With pantethine to protein mole ratios of 0.66, 1 and 2,
      the Tph of gamma II crystallin is lowered from 8 degrees C in the native protein,
      to 2 degrees C, -3 degrees C respectively, at a protein concentration of
      approximately equal to 200 mg/ml. The amount of gamma IIH accumulated decreases
      from approximately 25% in the native protein to 10%, 1% and 0% respectively in
      these pantethine-treated protein solutions. For complete suppression of the rise
      in Tph and inhibition of gamma IIH formation, a 2:1 mole ratio of pantethine to
      protein is required. CONCLUSIONS: We suggest that pantethine reacts with two
      cysteine residues of gamma IIH crystallin by forming a mixed disulfide, and
      effectively suppress protein aggregation and lowers Tph. This is due to the
      strong polar character of pantethine which reduces the net attractive
      interactions between the protein molecules.

PMID- 9018434
TI  - Separation and characterisation of cyclic nucleotide phosphodiesterases from the
      lacrimal, harderian and zygomatic glands of the rabbit.
AB  - PURPOSE: To investigate the activity profile of cyclic nucleotide
      phosphodiesterase (PDE) isoenzymes and the effects of isoenzyme selective
      inhibitors in the superior and inferior lacrimal glands, Harderian gland, and
      zygomatic gland of the rabbit. METHODS: Protein fractions extracted from crude
      homogenates on an anion exchange column were examined for PDE activity using an
      HPLC method for detecting nucleotides. RESULTS: The superior and inferior
      lacrimal glands had identified PDE activity profiles. PDE I was the major type of
      activity and there was also a minor PDE III peak of activity. The main activity
      detected in the lipid secreting Harderian gland was PDE II and for the mucus
      secreting zygomatic gland PDE III. All glands contained PDE IV activity. The
      kinetics of the peak enzyme activities were examined and found similar, but not
      identical to the kinetics for PDE activities obtained from other tissues.
      Inhibitors of specific PDE classes and the general PDE inhibitor, IBMX, were
      tested on the peak enzyme activities. Activities designated by their substrate
      specificity or co-factor modification were most strongly inhibited by the
      corresponding class selective inhibitor. For example, PDE I activity in the
      lacrimal gland was most strongly inhibited by nicardipine. All activities were
      inhibited by IBMX. CONCLUSIONS: The superior and inferior lacrimal glands of the
      rabbit have the same PDE profile and this differs from the PDE subtypes detected
      in the mucus secreting zygomatic gland and the lipid secreting Harderian gland.

PMID- 9018435
TI  - Effects of Ca2+ on rabbit translens short-circuit current: evidence for a Ca2+
      inhibitable K+ conductance.
AB  - PURPOSE: To characterize the effects of medium Ca2+ levels on rabbit lens
      electrical properties. Early studies with wholly submerged lenses had shown that
      Ca2+ removal from the bath resulted in an increased Rb+ efflux, a consequence of
      an increased Na+ Permeability and lens depolarization. METHODS: Lenses were
      bathed with Ussing-type chambers under short-circuited conditions, an arrangement
      in which the translens short-circuit current (Isc) is carried out across the
      posterior lens surface mainly by an influx of Na+, and across the anterior face
      largely by a K+ efflux. RESULTS: Under the present conditions in which the
      effects of Ca2+ were characterized unilaterally, the above established effects
      could only be ascribed to the posterior surface. When Ca2+ removal was limited to
      the anterior face, the Isc increased from 11.87 +/- 1.17 to 17.04 +/- 1.52
      microA/cm2 (means +/- SE's, n = 18; an accompanying translens resistance (Rt)
      decrease of 0.23 +/- 0.049 K omega.cm2 was also recorded). Conversely, increasing
      the control, anterior-bath [Ca2+] from 1.8 to 3.6 mM reduced the K+ efflux
      dependent Isc from 10.54 +/- 1.09 to 8.93 +/- 1.02 (n = 10, with an Rt increase
      of 0.11 +/- 0.013). These changes were reversible Na(+)-independent, and fully
      inhibited by the presence of K+ channel blockers (quinidine or Ba2+). Inhibitions
      of the Ca2+ effects were also obtained with strontium, a Ca2+ surrogate. The Isc
      was less responsive to changes in the Ca2+ content of the posterior bath. Removal
      of the cation caused a gradual 1.65 +/- 0.72 microA/cm2 increase (n = 9, with an
      Rt decrease of 0.090 +/- 0.021 K omega.cm2). In the absence of posterior Na+,
      Ca2+ withdrawal resulted in highly variable responses, with some specimens
      exhibiting salient current increases, suggesting that an outwardly directed,
      posterior efflux of an anion could also have been affected. During the course of
      this study it was consistently observed that the removal of Na+ from the anterior
      bath led to an Isc decrease of 2.62 +/- 0.22 microA/cm2 (n = 32, with an Rt
      increase of 0.35 +/- 0.029 k omega.cm2). This change occurred in both the
      presence of ouabain and the absence of Ca2+, suggesting that it did not result
      from an inhibition of the Na(+)-K+ pump current nor from a reversal in putative
      Na+/Ca2+ exchange activity. Small Isc increases upon anterior Na+ withdrawal
      (1.68 +/- 0.17, n = 7), consistent with Na+ efflux from the lens, could only be
      observed with K+ channels inhibited with Ba2+. Also congruent with the
      observations of a relatively limited anterior Na+ permeability, was the finding
      that the induction of nonspecific cation channels with amphotericin B reduced the
      Isc by following Na+ from the anterior bath to enter the lens. Thus, changes in
      lens Isc can differentiate changes in K+ permeability across the native anterior
      epithelium from changes in Na+ permeability. CONCLUSIONS: Overall, these results
      suggest that lens Ca2(+)-mobilizing agents (e.g. acetylcholine) could trigger the
      inhibition of epithelial K+ conductance(s) by the direct action of Ca2+ on K+
      channels.

PMID- 9018436
TI  - Increased synthesis of specific eicosanoids in rejected corneal grafts.
AB  - PURPOSE: Corneal injury stimulates the formation of both prostaglandins (PG) and
      12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), the major lipoxygenase
      metabolite. The purpose of this study was to investigate the metabolism of
      arachidonic acid (AA) in a model of corneal graft rejection. METHODS: Corneal
      tissue from Dutch belted rabbits was transplanted to vascularized corneas of New
      Zealand white rabbits. Rejected corneas were removed at the endstage of allograft
      failure. The allograft, the host corneal rim, the contralateral control cornea
      rim of equal size and normal Dutch belted cornea from the same site as the
      allograft were incubated with 0.25 microCi [3H]AA and the released eicosanoids
      were analyzed by high-performance liquid chromatography. RESULTS: The host
      corneal rims, adjacent to the failed allografts, produced up to five times as
      much 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) as contralateral control
      corneal rims. Additionally, prostaglandin E2 (PGE2) formation in the host rims
      increased 100% above controls, and 12(S)-HETE and PGE2 synthesis in the rejected
      corneal graft also increased. 12(R)-HETrE, an endogenous corneal angiogenic
      factor, was not detected in rejected corneas. CONCLUSIONS: The results point to
      the importance of selective AA pathways as the source key inflammatory components
      found in rejected allografts.

PMID- 9018437
TI  - New antiepileptic drugs.
AB  - For many years, the medical treatment of epilepsy was based on the use of the
      same few drugs, which were chosen according to the seizure type in a fairly
      standardized manner. In the recent past, there have been several changes, and
      more are expected in the near future. Since 1993, three new antiepileptic drugs
      have been released in the United States, and two more are expected to be released
      before the end of 1997. Because the full spectrum of efficacy and side effects of
      these drugs has not yet been established, the present management of epilepsy
      requires a larger degree of flexibility, and it is necessary to become acquainted
      with the new drugs and to follow closely new reports on the experience with new
      drugs. This is particularly true for the management of epilepsy in children,
      because controlled studies in children tend to be completed later than those in
      adults and antiepileptic drug use in children is often "off label." The present
      review of newer antiepileptic drug consists of a brief summary of background
      information on each drug, followed by a closer analysis of recently published
      papers. Information on pediatric use is reviewed, when available. The new
      antiepileptic drugs selected for discussion are gabapentin, lamotrigine,
      felbamate, vigabatrin, and topiramate.

PMID- 9018438
TI  - Brain tumors in children.
AB  - Primary central nervous system tumors are the second most common form of
      childhood cancer and the leading cancer-related cause of death and illness in
      children. Developments in neuroscience have led to an increasing understanding of
      these neoplasms, to alternations in their classification system, and to progress
      (albeit frustratingly slow progress) in their management. Chemotherapy has become
      an integral part of the treatment of many forms of childhood brain cancer,
      including medulloblastoma. Increasing evidence indicates that the amount of
      craniospinal radiation therapy required for diseases control can be reduced,
      possibly decreasing treatment-related sequelae, when this therapy is combined
      with postradiation chemotherapy. The value of the use of preradiation
      chemotherapy remains unproven. For other types of tumors, such as malignant high
      grade gliomas and brainstem gliomas, new approaches to therapy have not yet
      resulted in improved outcomes. However, even for these tumors, advances in
      neuroimaging and new neurobiologic approaches hold substantial promise.

PMID- 9018439
TI  - Gene therapy in neurology.
AB  - Many methods of gene transfer to the brain are under study for the treatment of
      the central nervous system manifestations of a number of diseases. One strategy
      employs vectors--typically genetically altered viruses--for the delivery of
      exogenous genes directly to a host's brain cells in situ. Alternatively,
      transplanting cells--of either neural or nonneural origin--that intrinsically
      secrete missing or therapeutic gene produces, or which are genetically engineered
      ex vivo to do so, may provide another strategy. Nonmigratory cells implanted into
      small, discrete anatomic sites are well suited for disease processes whose
      pathology is very focal. Neural cells that have the capacity to migrate in the
      central nervous system provide more powerful vehicles for delivering factors to
      disease involving pathology that is widely disseminated, extensive, multifocal,
      or even global (e.g., many neurogenetic diseases). Both neural and nonneural cell
      types have been successfully engineered to produce a variety of neurotransmitter
      synthetic enzymes, metabolic enzymes, and neurotrophic factors. Impressive
      results with genetically modified cells in animal models of central nervous
      system disease encourage the continued development of gene therapy strategies for
      treating neural dysfunction.

PMID- 9018440
TI  - Beyond dystrophin: current progress in the muscular dystrophies.
AB  - Major advances in the genetic understanding of the limb-girdle (LGMD) and
      congenital (CMD) muscular dystrophies have led to a new, genetically based
      classification of these disorders. The definition of the complex of dystrophin
      associated proteins on a biochemical and subsequently genetic level has greatly
      accelerated this progress by providing candidate genes to complement or replace
      the process of linkage analysis either in families with muscular dystrophy or in
      sporadic cases. The major components of the dystrophin-associated proteins now
      known to be involved in muscular dystrophy besides dystrophin itself ar the
      sarcoglycan complex and the alpha 2-chain (merosin) of laminin-2 in the
      extracellular matrix. Mutations in the various sarcoglycans account for four
      types of autosomal recessive LGMD of varying severity (types 2C through 2F),
      including severe childhood-onset presentations. One type of autosomal recessive
      LGMD (type 2A) is caused by mutations in the protease calpain-3, whereas the gene
      for type 2B has not yet been identified, although the responsible locus has been
      assigned to chromosome 2p13. There are different autosomal dominant forms as
      well, one of which has been mapped to chromosome 5q31. With regard to CMDs, the
      major breakthrough involves a type of "classic" CMD with abnormalities of the
      white matter on magnetic resonance imaging of the brain. These patients show
      deficiencies of the laminin alpha 2-chain, and mutations in the corresponding
      gene have been identified. The group of laminin alpha 2-chain-positive classic
      CMD likely is heterogeneous. Among the group of CMDs with abnormalities of brain
      formation and mental retardation, genetic, immunohistochemical, and clinical
      differences are now beginning to emerge to help in the distinction between
      Fukuyama muscular dystrophy, the Walker-Warburg syndrome, and muscle-eye-brain
      disease.

PMID- 9018441
TI  - A 35-week neonate with respiratory failure, hypotonia, and joint contractures.

PMID- 9018442
TI  - The etiology and control of bronchial hyperresponsiveness in children.
AB  - Bronchial hyperresponsiveness (BHR) describes the exaggerated bronchoconstrictor
      response to a host of stimuli such as cold air or exercise that occurs in most
      patients with asthma. It is an important feature of asthma because BHR correlates
      with diurnal peak expiratory flow variation, bronchospasm following exercise, the
      need for asthma medications, and asthma severity. Many studies published in the
      past year have increased our understanding of BHR. First, epidemiologic studies
      have revealed BHR to be a risk factor for the subsequent development of asthma.
      BHR is also more common in children than adults, and the persistence of BHR is
      related to atopy. Second, genetic and pathophysiologic studies have improved our
      understanding of the etiology of BHR. The genetic basis for BHR, atopy, and
      asthma was further elucidated with the finding of a cluster of potential
      candidate genes for asthma susceptibility on chromosome 5. In addition,
      eosinophilic infiltration and basement membrane thickening of the airways, both
      characteristic findings noted in patients with asthma, were found to correlate
      with pulmonary function and degree of BHR. Lastly, studies on treatment of BHR
      confirmed the beneficial effects of inhaled glucocorticoid therapy and allergen
      avoidance on BHR in children with asthma. In addition, a new type of asthma
      medication, the leukotriene inhibitors, has been shown to decrease BHR in adults
      with asthma and may eventually prove to be an effective medication for children
      with chronic asthma.

PMID- 9018443
TI  - Stinging insect hypersensitivity in children.
AB  - In the past two decades, many advances have been made in the treatment of
      patients with insect venom sensitivity. An effective treatment (venom
      immunotherapy) has been developed and indications for therapy refined. In the
      past year, reports concerning fatal toxic reactions to multiple stings,
      Africanized ("killer") bees, bumblebee venom allergy and treatment, and reactions
      to fire ant stings have been published. Papers have also appeared on the use of
      sting challenges in the diagnostic evaluation of insect sting allergy, laboratory
      investigations of the mechanism of action of venom immunotherapy, and the outcome
      of discontinuing venom treatment after 5 years in insect-allergic patients.

PMID- 9018444
TI  - Prospects for the prevention of allergy in children.
AB  - Allergic diseases are major causes of morbidity in children of all ages. Although
      improved treatment modalities have been developed for many of the allergic
      diseases, others, such as food allergy, have no available treatment. It would
      obviously be ideal if some allergic disease could be prevented. Although this
      approach is still in its early stages of development, a number of very
      encouraging studies have emerged in recent years. These studies are the focus of
      this review.

PMID- 9018445
TI  - Pediatric HIV infection.
AB  - Our ability to diagnose, treat, and prevent HIV infection in pregnant women and
      in children has changed dramatically over the last few years. Recent developments
      include "early diagnostic" techniques such as polymerase chain reaction,
      quantitative viral load measurements to assist in estimating disease status and
      prognosis, newer antiretroviral therapies (including combinations) and effective
      antibiotic prophylaxis for HIV-infected children, and a better understanding of
      maternal-fetal factors that may mediate transmission of HIV. As children with
      long-term immunosuppression live longer, we are diagnosing new diseases and
      unusual clinical manifestations of common diseases. Children are living into
      their teenage years with perinatally acquired HIV infection, and we now find
      ourselves dealing with many of the complex medical and psychosocial issues that
      have confronted clients with other chronic diseases (e.g., diabetes, cancer):
      issues of growth failure; nutrition; depression' disclosure of illness to school,
      friends, and family; and death and dying. What separates HIV from other chronic
      diseases is its ability to infect and affect so many other family members, not
      just the child.

PMID- 9018446
TI  - Genetics and the population.

PMID- 9018447
TI  - Genetic and clinical advances in Prader-Willi syndrome.
AB  - Prader-Willi syndrome is a developmental disorder with distinctive dysmorphic
      features, specific neurobehavioral attributes, and a characteristic learning
      profile. Advances continue to be made in understanding the factors associated
      with the loss of imprinted gene expression within chromosome 15q11-q13. These
      advances are helping providers make certain diagnoses early and are helping
      scientists uncover new genetic pathways. In addition, efforts to further
      understand the role of recombinant growth hormone therapy in Prader-Willi
      syndrome and the genetic information responsible for the neurobehavioral profile
      are additional targets for research.

PMID- 9018448
TI  - Heterozygote screening for Tay-Sachs disease: past successes and future
      challenges.
AB  - Tay-Sachs disease (TSD) is an autosomal recessive, neurodegenerative disorder
      caused by a deficiency of beta-hexosaminidase A activity. Mass screening for TSD
      heterozygotes has been routine in the Ashkenazi Jewish population since the early
      1970s. Recent advances in the molecular genetics and epidemiology of TSD require
      a reevaluation of heterozygote screening practices. The use of DNA-based analyses
      for a panel of common mutations detects about 98% of TSD mutations found in the
      Ashkenazi Jews and about 50% of TSD mutations found in the general non-Jewish
      population; enzyme-based analysis has nearly 100% sensitivity for all
      populations. We recommend 1) that members of several ethnic groups and persons
      with a family history consistent with TSD be offered testing for TSD
      heterozygosity and 2) that assays of enzyme activity be used as the primary
      screening tool, with mutation analysis used as an adjunct tool in certain cases.

PMID- 9018449
TI  - Folic acid in the prevention of birth defects.
AB  - Maternal use of folic acid prior to conception reduces the risk for neural tube
      defects. In addition, other birth defects may be prevented by the
      periconceptional use of folic acid. Homocysteine-methionine metabolism appears to
      be altered in women with pregnancies affected by neural tube defects; however,
      the specific mechanisms of causation are not yet known. Fortification of flour
      with folic acid has been approved by the Food and Drug Administration, although
      at a level that still requires folic acid supplementation as recommended by the
      Public Health Service for all women of childbearing age to prevent neural tube
      defects.

PMID- 9018450
TI  - Population screening for cystic fibrosis.
AB  - In the 7 years since the cystic fibrosis (CF) gene has been cloned, many
      experimental trials of population screening for CF heterozygotes have been
      reported. Targeting young adults near reproductive age has shown that the method
      in which screening is offered is a major determinant of acceptance rates:
      personal invitations produce high rates of acceptance, whereas offers made by
      mail or leaflet produce disappointing results. In contrast, trials of screening
      during pregnancy have been more satisfactory. Two models have been tested. In
      sequential screening, women are screened first and their partners are tested only
      if the women are found positive for CF alleles. This can lead to anxiety during
      the period when women who have tested positive await their partner's results. In
      couple screening both partners agree to be treated as a unit and are reported to
      be "high risk" only if both results are positive. In all other situations, the
      results are reported to be negative. Couple screening has turned out to be
      efficient, trouble-free, and consumer-friendly and may be the method of choice
      for integration into routine health care.

PMID- 9018451
TI  - Office laboratory procedures, office economics, patient and parent education, and
      urinary tract infection.
AB  - This review updates our readers on four important areas of office practice:
      office laboratory procedures, office economics, patient and parent education, and
      urinary tract infection. Michael Aldous reviews the recent literature on office
      laboratory procedures, which includes a report on the ongoing heated discussion
      of the Clinical Laboratory Improvement Amendments, an update of recent studies on
      new and better rapid streptococcal tests, and improved methods for urinalysis.
      Rickey Williams provides a report on office economics that includes a discussion
      of the effects of capitation, how preventive care can be cost effective, and the
      future prospects for greatly expanded office computerization. Burris Duncan
      discusses patient and parent education with an in-depth review of the potential
      economic value of a full implementation of the American Academy of Pediatrics'
      The Injury Prevention Program, and in addition he chronicles the rapid growth and
      development of school-based health centers. John Ey reviews the recent literature
      on urinary tract infections in children, including how we can make the diagnosis,
      methods for preventing recurrent urinary tract infections, the most effective
      studies for evaluating the urinary system, and what follow-up is necessary. We
      hope this review will provide the pediatrician with important information to help
      in the care of their patients.

PMID- 9018452
TI  - Assessment of disease activity and its sequelae in children and adults with
      myositis.
AB  - Validated, comprehensive measures for assessing disease activity and its
      irreversible sequelae, known as disease damage, have not been developed for the
      idiopathic inflammatory myopathies (IIM), thus limiting our capacity to assess
      individual patients and responses to therapies. This review summarizes current
      approaches for assessing disease activity and damage in the idiopathic
      inflammatory myopathies and speculates on possibly useful novel approaches for
      the future. Disease activity and damage indices that combine a number of these
      assessments are proposed for use in all therapeutic trials. Methods for assessing
      target organs of the idiopathic inflammatory myopathies will likely evolve as
      more sensitive and specific measures are developed that can distinguish active
      inflammation from the irreversible effects of disease.

PMID- 9018453
TI  - Infectious agents associated with myopathies.
AB  - Several infectious agents can cause chronic or acute myopathy. Most current
      investigations into possible infectious causes of the idiopathic inflammatory
      myopathies have focused on retroviruses, including HIV and human T-cell leukemia
      lymphoma virus type I. In both cases, viruses likely do not directly infect
      muscle fibers but instead induce an immunologically mediated myositis. Other
      interest has focused on enteroviruses as potential etiologic agents of idiopathic
      inflammatory myopathy, but their relationship to human myositis is less clear. In
      addition to chronic muscle disease, several infectious agents can cause acute
      myositis, including pyomyositis, which is being recognized in temperate climates
      with increasing frequency, and rhabdomyolysis.

PMID- 9018454
TI  - Genetics of the idiopathic inflammatory myopathies.
AB  - Genetic predisposition to development of the idiopathic inflammatory myopathies
      is probably multifactorial. Major histocompatibility complex associations with
      these diseases provide the strongest evidence for a genetic component. In
      Caucasoids, haplotypes marked by B8/DR3 are associated with each of the clinical
      subgroups, except mixed connective tissue disease (DR4). The strongest
      associations are with inclusion body myositis, polymyositis in the presence of
      anti-Jo-1, and with antibodies to PM-Scl in overlap syndromes. The underlying
      mechanisms of these associations are probably different. Unique major
      histocompatibility complex associations are seen with other myositis-associated
      autoantibodies. The association can vary between racial groups as can the type of
      autoantibody produced within a disease subgroup, perhaps reflecting different T
      cell receptor repertoires or different inducing agents. The mapping of a gene for
      one form of hereditary inclusion body myositis to chromosome 9p1-q1 provides a
      lead for the investigation of sporadic inclusion body myositis, as does the
      expanding knowledge of genetic factors in Alzheimer's disease. The demonstration
      of deletions of mitochondrial DNA in the muscle of patients with inclusion body
      myositis raises the question of their role in the pathogenesis of the disease.

PMID- 9018455
TI  - Structures targeted by the immune system in myositis.
AB  - Polymyositis and dermatomyositis are characterized by the production of a series
      of autoantibodies to various cellular constituents. Some of these autoantibodies
      are found specifically in patients with polymyositis or dermatomyositis or
      myositis overlap syndrome and predict clinical subgroups and prognosis. If we are
      to understand the etiology and pathogenic mechanisms of polymyositis and
      dermatomyositis, it will be particularly important to elucidate the structure and
      function of target autoantigens recognized by these myositis-specific
      autoantibodies. In recent years, many autoantigens and some epitopes have been
      identified using molecular biology approaches. During the 1-year period reviewed
      here, the nature and function of the Mi-2 and the Ku(p70/p80) antigens which are
      recognized by autoantibodies in patients with dermatomyositis and with the
      myositis overlap syndrome, respectively, have been elucidated. Several new
      autoantibodies that are not specific for but that are associated with myositis
      have also been described.

PMID- 9018456
TI  - HyperCKemic, proximal muscular dystrophies and the dystrophin membrane
      cytoskeleton, including dystrophinopathies, sarcoglycanopathies, and
      merosinopathies.
AB  - Of the various muscular dystrophies, the dystrophinopathies are the most common,
      accounting for the majority of male muscle disease patients and for about 10% of
      female patients referred for the evaluation of muscular dystrophy or persistent
      high serum creatine kinase values (hyperCKemia). The approach to diagnosis and
      family genetic counseling for the dystrophinopathies is now well established, and
      implementation of carrier detection and prenatal diagnosis has dramatically
      decreased the incidence of familial cases. With the decreasing observation of a
      positive family history in newly ascertained cases, molecular genetic and protein
      studies become imperative for accurate diagnosis. Genetic counseling in families
      of isolated cases can still be problematic. There is a wide range of opinions
      regarding the management of Duchenne muscular dystrophy, with surgical
      interventions (eg, tendon lengthenings and spinal fusion), steroid use, and
      extent of respiratory support actively debated. There has been progress in
      defining the underlying cause of disease for some patients of muscular dystrophy
      who have normal dystrophin findings. Nearly all patients with proximal,
      hyperCKemic muscular dystrophy who have normal dystrophin show no family history
      of the disorder, consistent with autosomal recessive disease. Approximately 5% of
      both boys and girls with childhood-onset dystrophy and normal dystrophin have
      been found to have mutations in one of the four sarcoglycan proteins identified
      to date. Also, approximately half of the patients with congenital muscular
      dystrophy show deficiency of a component of the muscular extracellular matrix.
      (merosin/laminin-alpha 2). In this review, we give a short primer on relevant
      muscle structure and function, followed by a series of case reports on patients
      referred for molecular testing that illustrate the diagnostic protocols, range of
      clinical presentations, and genetic counseling options in the work-up of proximal
      muscular dystrophy and hyperCKemia.

PMID- 9018457
TI  - Progress, problems, and prospects for gene therapy in muscle.
AB  - As the molecular defects that cause many muscle diseases have been identified,
      research has shifted to finding novel therapies. Gene therapy has been proposed
      both for correcting primary gene defects of muscle and as a way of using muscle
      for the production of proteins therapeutic in inflammatory or nonmuscle diseases.
      Several strategies have been developed to introduce foreign genes into diseased
      muscles, including myoblast transfer, direct injection of plasmids or DNA
      liposome complexes, and infection with modified viruses. Related strategies,
      using antisense sequences or ribozymes, have been devised to modify gene
      expression in diseased cells. No method has yet proved itself in the clinic,
      although current work remains promising and some of the pitfalls that must be
      overcome have been identified.

PMID- 9018458
TI  - Update on therapy for refractory dermatomyositis and polymyositis.
AB  - Evaluation of new therapies for the inflammatory myopathies is complicated by the
      heterogeneity of these syndromes as well as by the lack of internationally
      accepted definitions of disease categories and assessments of disease activity
      and chronicity. This review covers our opinion of therapies and emphasizes the
      need for an early rehabilitation evaluation for these patients. Oral
      corticosteroids are the first line of therapy for the inflammatory myopathies,
      but because of their side effects and the existence of a subset of patients in
      whom disease is controlled only with high-dose corticosteroids, we recommend
      considering the early use of a second-line immunomodulating agents or pulse
      intravenous methylprednisolone. A stepwise progression of therapies is suggested
      for patients who have increasing muscle weakness resulting from active disease.

PMID- 9018459
TI  - Advances in palliative care for the patient with scleroderma.
AB  - Few studies published within the past year have addressed palliative care for the
      patient with scleroderma or systemic sclerosis. However, progress continues to be
      made, and important contributions have been made with respect to different
      vasodilator preparations for Raynaud's phenomenon, a possible role for diltiazem
      in the treatment of calcinosis, and the treatment of gut dysmotility. A number of
      comprehensive review papers on different aspects of management, mainly organ
      based, were included in the recently published textbook Systemic Sclerosis. Until
      there is an effective disease-modifying treatment for systemic sclerosis,
      management will be largely palliative and is best delivered by a
      multidisciplinary team.

PMID- 9018460
TI  - Raynaud's phenomenon and other features of scleroderma, including pulmonary
      hypertension.
AB  - Longitudinal studies of large cohorts of patients with Raynaud's Phenomenon have
      addressed the predictors of developing a secondary disease. New insights have
      been reported into the pathogenesis of Raynaud's phenomenon and the consequences
      of ischemia. Studies have suggested that more than one defect may cause Raynaud's
      phenomenon, including increased alpha-2 sympathetic receptor activity on vessels,
      endothelial dysfunction, deficiency of calcitonin gene related peptide protein-
      containing nerves or some central thermoregulatory defect. The vasoconstricting
      and profibrotic cytokine endothelin-1 was found to be elevated in scleroderma but
      did not correlate with disease subset or with evidence of pulmonary hypertension.
      Oxidant stress is thought to be increased in scleroderma, causing tissue damage
      and provoking fibrosis. Treatment with infusion of prostacyclin for primary
      pulmonary hypertension was approved, paving the way for studies of secondary
      forms of pulmonary hypertension. Oral prostanoids are being tested for the
      treatment of Raynaud's phenomenon.

PMID- 9018461
TI  - Gastrointestinal features of scleroderma.
AB  - Gastrointestinal involvement occurs in most patients with systemic sclerosis and
      is subclinical in about one third. Early pathology is characterized by
      vasculopathy, resulting in tissue ischemia and progressive dysfunction.
      Noninvasive esophageal studies using semisolid bolus scintigraphy are sensitive
      but lack specificity. Long-term treatment of reflux with high-dose proton pump
      inhibitors appears safe and effective for symptom relief and may prevent
      recurrence of esophagitis and stricture. Dyspepsia may result from gastroparesis
      and antral distension. Gastric antral vascular ectasia is a vascular
      manifestation, and bleeding may be controlled endoscopically. Prokinetic agents
      effective in pseudoobstruction include metoclopramide, domperidone, cisapride,
      octreotide, and erythromycin. Patients with intestinal neuropathy or response to
      bolus octreotide are more probable long-term responders. The combination of
      octreotide and erythromycin may be particularly effective in systemic sclerosis.
      The combination of cisapride and erythromycin may cause serious cardiac
      arrhythmia and is contraindicated. Omeprazole may predispose to small intestinal
      bacterial overgrowth. Malabsorption not responding to antibiotic therapy should
      be investigated with small-bowel biopsy to rule out more unusual causes.
      Pneumatosis cystoides intestinalis may be due to excessive hydrogen production by
      intestinal bacteria altering the partial pressure of nitrogen in the intestinal
      wall. In selected cases, surgery for intestinal failure is an option with
      resection or bypass of affected segments or placement of enterostomy tubes for
      feeding or decompression. Careful preoperative characterization of intestinal
      segments is required.

PMID- 9018462
TI  - Systemic and localized scleroderma in children.
AB  - All forms of scleroderma are rare in childhood. The most common form in childhood
      is localized scleroderma, which may take the form of morphea or linear
      scleroderma. Localized scleroderma is often benign but may cause significant
      deformity if it occurs on the face or extends across joint surfaces. Progressive
      systemic sclerosis is much less frequent in childhood but may have a rapidly
      progressive and ultimately fatal course. CREST (calcinosis, Raynaud's phenomenon,
      esophageal dysfunction, sclerodactyly, and telangieactasia) syndrome also may
      occur in childhood with manifestations similar to those seen in adults. In
      addition, some children in whom mixed connective tissue disease is initially
      diagnosed ultimately develop progressive systemic sclerosis. Research into both
      the causes and the optimal therapy for childhood scleroderma is hampered by the
      small number of patients treated at individual centers. This limitation has made
      it difficult to perform well-controlled studies.

PMID- 9018463
TI  - Connective tissue metabolism in scleroderma, including cytokines.
AB  - The recent literature on scleroderma emphasizes the importance of cytokine
      dysregulation, cell-cell interactions, and extracellular matrix overproduction in
      the pathogenesis of this disease. Advances in our understanding of these areas
      are discussed here.

PMID- 9018465
TI  - Myositis and myopathies.

PMID- 9018464
TI  - Epidemiology of systemic sclerosis.
AB  - There have been few recent studies of the descriptive epidemiology of systemic
      sclerosis, but in recent work the limited form of the disease seems more
      prominent than reported in previous studies. Molecular genetic investigation of
      systemic sclerosis remains disappointing in identifying susceptibility alleles.
      There are some associations in relation to HLA class II alleles, specifically DP,
      DQ, and DR. These associations, however, seem to be more important in predicting
      the nature of the autoimmune response rather than describing disease
      susceptibility itself. The study of occupational and environmental influences has
      been dominated by studies on the role of silicone gel breast implants. These
      studies, driven by medicolegal constraints, have overwhelmingly failed to prove
      any association. Other studies confirm the continuing likelihood that organic
      solvents are implicated, at least in a proportion of cases.

PMID- 9018466
TI  - Raynaud's phenomenon, scleroderma, overlap syndromes, and other fibrosing
      syndromes.

PMID- 9018467
TI  - Superoxide dismutase activity and lipid peroxidation in the liver of guinea pig
      infected with Leptospira interrogans.
AB  - Superoxide dismutase (SOD) activity and the degree of lipid peroxidation were
      studied over a two week period in guinea pigs infected with Leptospira
      interrogans derived from wild mice. The total SOD activity in infected host liver
      increased by four-fold two days after infection; this was followed by a 20%
      decrease resulting in levels comparable to normal, uninfected liver. During the
      period of decreasing SOD activity after day two, the levels of TBA-reactive
      material (TBARS) are increased by three-fold in infected guinea pig, liver,
      compared to uninfected liver. The results indicate that SOD attenuates
      intracellular superoxide-mediated toxic effects in guinea pigs infected with L.
      interrogans. In addition, electron microscopy structure demonstrates correlated
      pathogenic shrinkage of mitochondrial and Kupffer cell structures.

PMID- 9018469
TI  - Multicomponent investigations of the hydrogen peroxide- and hydroxyl radical
      scavenging antioxidant capacities of biofluids: the roles of endogenous pyruvate
      and lactate. Relevance to inflammatory joint diseases.
AB  - High field proton (1H) nuclear magnetic resonance (NMR) analysis of biofluids
      (health human blood sera and inflammatory knee-joint synovial fluids) has been
      employed to evaluate the hydrogen peroxide (H2O2)- and hydroxyl radical (0OH)-
      scavenging antioxidant capacities of a range of polar, low-molecular-mass
      endogenous metabolites therein. Data obtained indicate that consumption of H2O2
      by pyruvate (generating acetate and CO2 via an oxidative decarboxylation
      reaction) and 0OH radical by lactate (generating pyruvate, and subsequently
      acetate and CO2) may serve to protect alternative biofluid components (e.g.,
      macromolecules) against reactive oxygen species-mediated oxidative damage in
      vivo. The mechanistic, physiological and potential therapeutic implications of
      these results are discussed with special reference to inflammatory joint
      diseases.

PMID- 9018468
TI  - Superoxide-mediated reduction of the nitroxide group can prevent detection of
      nitric oxide by nitronyl nitroxides.
AB  - Nitronyl nitroxides (NN), a class of compounds which react with nitric oxide
      forming imino nitroxides, were applied in different systems for the detection of
      nitric oxide. Addition of a NN to planar monolayers of bovine aortic endothelial
      cells (BAEC) activated by Ca2+ ionophore A23187 immediately resulted in a strong
      decrease of the ozone-mediated .NO chemiluminescence. Simultaneously, a rapid
      diminution of the electron spin resonance (ESR) signal intensity of the NN
      (without detectable formation of the corresponding imino nitroxide) was observed;
      superoxide dismutase partially inhibited this decrease in the NN concentration.
      Model experiments using hypoxanthine/xanthine oxidase in aqueous solution and KO2
      in dimethylsulfoxide as sources of O2.- revealed that there is a rapid reduction
      of nitronyl nitroxides by superoxide. The second order rate constant for the
      reaction of the water soluble NN with O2.- was determined to be 8.8 x 10(5) M-1s
      1, which is more than two orders of magnitude higher than the value reported
      previously for reaction with .NO (Woldman et al., BBRC 202, 195-203, 1994).
      Reduction of the nitronyl nitroxide was also observed in the presence of
      glutathione, ascorbic acid or rabbit liver microsomes. Incorporation of both
      nitronyl and imino nitroxides into liposomes strongly decreased reduction by
      superoxide and other reductants, however, in the presence of microsomes, there
      was no protective effect by liposomal encapsulation of NN. The results indicate
      that in biological systems (in addition to other reducing agents) the presence of
      superoxide can prevent the detection of nitric oxide using nitronyl nitroxides.

PMID- 9018470
TI  - The antioxidant Trolox enhances the oxidation of 2',7'-dichlorofluorescin to
      2',7'-dichlorofluorescein.
AB  - The use of antioxidants to prevent intracellular free radical damage is an area
      currently attracting considerable research interest. The compound 2',7'
      dichlorofluorescin diacetate (DCFH-DA) is a probe for intracellular peroxide
      formation commonly used in such studies. During our studies we unexpectedly found
      that incubation of Trolox, a water soluble vitamin E analog, with DCFH-DA in cell
      free physiological buffers resulted in the deacetylation and oxidation of DCFH-DA
      to form the fluorescent compound, 2',7'-dichlorofluorescein (DCF). The reaction
      was time-, temperature-, and pH-dependent. Fluorescence intensity increased with
      an increase in either Trolox or DCFH-DA concentration. These results indicate
      that even at physiological pH, DCFH-DA can be deacetylated to form 2',7'
      dichlorofluororescin (DCFH), DCFH can then be oxidized to DCF by abstraction of a
      hydrogen atom by the phenoxyl radical of Trolox. Exposure of the reaction mixture
      to 10 Gy of 60Co gamma radiation greatly increased production of DCF. Antioxidant
      compounds reported to "repair" the Trolox phenoxyl radical (e.g., ascorbic acid,
      salicylate) can also prevent the Trolox-induced DCFH-DA fluorescence. However,
      radical (e.g., catechin) or can themselves form a radical (e.g., uric acid,
      TEMPOL) either have no effect or can increase levels of DCF. These results
      demonstrate that experimental design must be carefully considered when using DCFH
      DA to measure peroxide formation in combination with certain antioxidants.

PMID- 9018471
TI  - Prevention of peroxynitrite-dependent tyrosine nitration and inactivation of
      alpha1-antiproteinase by antibiotics.
AB  - Peroxynitrite, formed by reaction of superoxide and nitric oxide, appears to be
      an important tissue damaging species generated at sites of inflammation. In this
      paper, we compare the abilities of several antibiotics to protect against
      peroxynitrite-dependent inactivation of alpha1-antiproteinase, and to inhibit
      tyrosine nitration by peroxynitrite, in vitro. Tetracycline, minocycline,
      doxycycline, rifamycin and rifampicin were highly protective in both assay
      systems, whereas several other antibiotics tested were not. The possibility that
      antibiotics could affect tissue injury at sites of inflammation by scavenging
      peroxynitrite is discussed.

PMID- 9018472
TI  - 2-Hydroxy-succinaldehyde, a lipid peroxidation product proving that
      polyunsaturated fatty acids are able to react with three molecules of oxygen.
AB  - 2-Hydroxy-succinaldehyde was detected by a GC/MS analysis of trapped aldehydic
      compounds obtained after Fe2+/ascorbate lipid peroxidation of arachidonic acid.
      Precursor molecules of aldehydes are hydroperoxy compounds. Thus the generation
      of the two aldehydic groups in 2-hydroxysuccinaldehyde requires a precursor
      molecule with two hydroperoxy groups. The hydroxy group in 2-position is
      generated by a third hydroperoxidation reaction. The detection of 2
      hydroxysuccinaldehyde--although found only in traces--is the first example for
      triple dioxigenation of unsaturated fatty acid. Linolenic acid produces 2
      hydroxysuccinaldehyde in much lower amounts than arachidonic acid. A similar
      oxidation of linoleic acid was not observed.

PMID- 9018473
TI  - Antioxidant activity of phytoestrogenic isoflavones.
AB  - The aim of this work was to determine the antioxidant activities of a range of
      phytoestrogenic isoflavones. The antioxidant activity in the aqueous phase was
      determined by means of the ABTS.+ total antioxidant activity assay. The results
      show that the order of reactivity in scavenging the radical in the aqueous phase
      is genistein > daidzein = genistin approximately equal to biochanin A = daidzin >
      formononetin approximately equal to ononin, the latter displaying no antioxidant
      activity. The importance of the single 4'-hydroxyl group in the reactivity of the
      isoflavones, as scavengers of aqueous phase radicals, as well as the 5'7
      dihydroxy structure is demonstrated. Examination of their abilities to enhance
      the resistance of low density lipoproteins to oxidation supports the observation
      that genistein is the most potent antioxidant among this family of compound
      studied, both in the aqueous and in the lipophilic phases.

PMID- 9018474
TI  - Peroxynitrite-dependent aromatic hydroxylation and nitration of salicylate and
      phenylalanine. Is hydroxyl radical involved?
AB  - There is considerable dispute about whether the hydroxylating ability of
      peroxynitrite (ONOO-)- derived species involves hydroxyl radicals (OH.). This was
      investigated by using salicylate and phenylalanine, attack of OH. upon which
      leads to the formation of 2,3- and 2,5-dihydroxybenzoates, and o- m- and p-
      tyrosines respectively. On addition of ONOO- to salicylate, characteristic
      products of hydroxylation (and nitration) were observed in decreasing amounts
      with rise in pH, although added products of hydroxylation of salicylate were not
      recovered quantitatively at pH 8.5, suggesting further oxidation of these
      products and underestimating of hydroxylation at alkaline pH. Hydroxylation
      products decreased in the presence of several OH. scavengers, especially formate,
      to extents similar to those obtained when hydroxylation was achieved by a mixture
      of iron salts, H2O2 and ascorbate. However, OH. scavengers also inhibited
      formation of salicylate nitration products. Ortho, p- and m-tyrosines as well as
      nitration products were also observed when ONOO- was added to phenylalanine. The
      amount of these products again decreased at high pH and were decreased by
      addition of OH. scavengers. We conclude that although comparison with Fenton
      systems suggests OH. formation, simple homolytic fission of peroxynitrous acid
      (ONOOH) to OH. and NO2. would not explain why OH. scavengers inhibit formation of
      nitration products.

PMID- 9018475
TI  - Purification and properties of cytosolic copper, zinc superoxide dismutase from
      watermelon (Citrullus vulgaris Schrad.) cotyledons.
AB  - Cytosolic copperzinc-superoxide dismutase (CuZn-SOD I; EC 1.15.1.1) was purified
      to homogeneity from watermelon (Citrullus vulgaris Schrad.) cotyledons. The
      stepwise purification procedure consisted of acetone precipitation, batch anion
      exchange chromatography, anion-exchange Fast Protein Liquid Chromatography, gel
      filtration column chromatography, and affinity chromatography on concanavalin A
      Sepharose. CuZn-SOD I was purified 310-fold with a yield of 12.6 micrograms
      enzyme per gram cotyledons, and had a specific activity of 3,450 units per
      milligram protein. The relative molecular mass for cytosolic CuZn-SOD was 34000,
      and it was composed by two equal subunits of 16.3 kDa. CuZn-SOD I did not contain
      neutral carbohydrates in its molecule, and its ultraviolet and visible absorption
      spectra showed two absorption maxima at 254 nm and 580 nm. Metal analysis showed
      that the enzyme contained 1 gram-atom Cu and 1 gram-atom Zn per mole dimer.
      Cytosolic CuZn-SOD was recognized by the antibody against peroxisomal CuZn-SOD
      from watermelon cotyledons, and its enzymatic activity was inhibited by this
      antibody. By IEF (pH 4.2-4.9), using a new method for vertical slab gels set up
      in our laboratory, purified cytosolic CuZn-SOD was resolved into two equal
      isoforms with isoelectric point of 4.63 and 4.66.

PMID- 9018476
TI  - Eccentric contractions require unique activation strategies by the nervous
      system.
AB  - Eccentric contractions occur when activated muscles are forcibly lengthened. This
      mode of muscle function occurs frequently in the activities of daily living and
      in athletic competition. This review examines the experimental evidence that
      provides the foundation for our current understanding of the benefits,
      consequences, and control of eccentric contractions. Over the past several
      decades, numerous studies have established that eccentric contractions can
      maximize the force exerted and the work performed by muscle; that they are
      associated with a greater mechanical efficiency; that they can attenuate the
      mechanical effects of impact forces; and that they enhance the tissue damage
      associated with exercise. More recent evidence adds a new feature to this
      repertoire by suggesting a new hypothesis: that the neural commands controlling
      eccentric contractions are unique. Examination of this hypothesis is critical
      because the existence of such a control scheme would increase substantially the
      complexity of the strategies that the nervous system must use to control
      movement.

PMID- 9018477
TI  - "Pulmonary chemoreflex elicited by intravenous injection of lactic acid in
      anesthetized rats".

PMID- 9018478
TI  - Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in
      anesthetized rats.
AB  - Experiments were carried out to characterize the cardiorespiratory reflex
      responses to intravenous injection of lactic acid and to determine the
      involvement of vagal bronchopulmonary C-fiber afferents in eliciting these
      responses in anesthetized rats. Bolus injection of lactic acid (0.2 mmol/kg i.v.)
      immediately elicited apnea, bradycardia, and hypotension, which were then
      followed by a sustained hyperpnea. The immediate apneic and bradycardiac
      responses to lactic acid were completely abolished by bilateral vagotomy and were
      absent when the same dose of lactic acid was injected into the left ventricle.
      The subsequent hyperpneic response was substantially attenuated by denervation of
      carotid body chemoreceptors. After a perineural capsaicin treatment of both vagus
      nerves to block the conduction of C fibers, lactic acid no longer evoked the
      immediate apnea and bradycardia, whereas the hyperpneic response became more
      pronounced and sustained, presumably because of the removal of the inhibitory
      effect on breathing mediated by pulmonary C-fiber activation. Single-unit
      electrophysiological recording showed that intravenous injection of lactic acid
      consistently evoked an abrupt and intense burst of discharge from the vagal C
      fiber afferent endings in the lungs. In conclusion, the cardiorespiratory
      depressor responses induced by lactic acid are predominantly elicited by
      activation of vagal pulmonary C fibers.

PMID- 9018479
TI  - Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced
      neurogenic inflammation.
AB  - We investigated the role of neurogenic inflammation and the subsequent mechanisms
      in cigarette smoke-induced airway hyperresponsiveness in guinea pigs. Exposure to
      cigarette smoke was carried out at tidal volume for 3 min. Airway responsiveness
      to histamine was determined before and after smoke exposure followed by
      bronchoalveolar lavage (BAL). Plasma extravasation was evaluated by measuring the
      extravasation of Evans blue dye in the airway. Cigarette smoke produced
      significant airway hyperresponsiveness and plasma extravasation, with an influx
      of neutrophils in BAL fluid. FK-224 (10 mg/kg i.v.), a tachykinin antagonist at
      NK1 and NK2 receptors, significantly inhibited these changes. The thromboxane
      (Tx) B2 concentration was increased in BAL fluid after smoke exposure and was
      significantly inhibited by FK-224. OKY-046 (10 mg/kg i.v.), a Tx synthase
      inhibitor, significantly inhibited airway hyperresponsiveness but had no effect
      on neutrophil influx or plasma extravasation. The results suggest that neurogenic
      inflammation and the subsequent generation of Tx in the airway are important in
      the development of the airway hyperresponsiveness induced by cigarette smoke.

PMID- 9018480
TI  - Regional blood flows in the goat latissimus dorsi muscle before and after chronic
      stimulation.
AB  - Latissimus dorsi muscle (LDM) regional blood flows were determined in
      anesthetized goats by using colored microspheres under noncontracting and
      contracting conditions, either before or after 8-10 wk of chronic muscle
      stimulation. Surgical dissection of the LDM, leaving only the thoracodorsal
      artery to supply the muscle, did not alter regional noncontracting blood flows
      but significantly reduced the normal hyperemic response to muscle contraction in
      muscle regions (posterior-medial) furthest from the entrance of the thoracodorsal
      artery. Eight to 10 wk after acute muscle dissection, posterior-medial hyperemic
      flows were restored. Chronic stimulation of the LDM for 8-10 wk, in either
      dissected or nondissected muscles, did not alter regional blood flows in
      noncontracting muscle; however, it significantly reduced hyperemic flows in all
      muscle regions, although capillary density was increased and the muscle was
      transformed into a predominantly type I fiber type. These results, coupled with
      data from previous experiments, suggest that the muscle damage observed in the
      posterior-medial regions of the LDM after surgical dissection and chronic
      stimulation may be related to reduced hyperemic flow responses caused by surgical
      isolation of the muscle.

PMID- 9018481
TI  - Lung tissue behavior in the mouse during constriction induced by methacholine and
      endothelin-1.
AB  - Recently, mice have been extensively used to investigate the pathogenesis of
      pulmonary disease because appropriate murine models, including transgenic mice,
      are being increasingly developed. However, little information about the lung
      mechanics of mice is currently available. We questioned whether lung tissue
      behavior and the coupling between dissipative and elastic processes,
      hysteresivity (eta), in mice would be different from those in the other species.
      To address this question, we investigated whether tissue resistance (Rti) and eta
      in mice would be affected by varying lung volume, constriction induced by
      methacholine (MCh) and endothelin-1 (ET-1), and high-lung-volume challenge during
      induced constriction. From measured tracheal flow and tracheal and alveolar
      pressures in open-chest ICR mice during mechanical ventilation [tidal volume = 8
      ml/kg, frequency (f) = 2.5 Hz], we calculated lung resistance (RL), Rti, airway
      resistance (Raw), lung elastance (EL), and eta (= 2piRti/EL). Under baseline
      conditions, increasing levels of end-expiratory transpulmonary pressure decreased
      Raw and increased Rti. The administration of aerosolized MCh and intravenous ET-1
      increased RL, Rti, Raw, and EL in a dose-dependent manner. Rti increased from
      0.207 +/- 0.010 to 0.570 +/- 0.058 cmH2O.ml-1.s after 10(-7) mol/kg ET-1 (P <
      0.01). After induced constriction, increasing end-expiratory transpulmonary
      pressure decreased Raw. However, eta was not affected by changing lung volume,
      constriction induced by MCh and ET-1, or high-lung-volume challenge during
      induced constriction. These observations suggest that 1) eta is stable in mice
      regardless of various conditions, 2) Rti is an important fraction of RL and
      increases after induced contriction, and 3) mechanical interdependence may affect
      airway smooth muscle shortening in this species. In mammalian species, including
      mice, analysis of eta may indicate that both Rti and EL essentially respond to a
      similar degree.

PMID- 9018482
TI  - Effect of vitamin E deprivation and exercise training on induction of HSP70.
AB  - To investigate the effect of dietary vitamin E deprivation and chronic exercise
      on the relative content of selected isoforms of the heat-shock protein 70 (HSP70)
      family in rat hindlimb muscle, vitamin E was withheld for 16 wk from female rats
      that underwent treadmill run training during the final 8 wk. As indicated by
      increased (P < 0.05) content of the stress-inducible isoform (HSP72), training
      did stress the exercising muscles. However, vitamin E deficiency did not alter
      HSP72 content in nontrained rats and was associated with a lesser induction (P <
      0.01) in some muscles of trained animals. The constitutive isoform, which
      exhibited similar levels in muscles of varying fiber types, was demonstrated to
      be largely refractory to exercise, with an equivocal response to vitamin E
      deprivation. HSP72 content was correlated to type I myosin heavy chain (MHC-I)
      content but only in muscles of sedentary normal-diet rats. After training, HSP72
      content in a muscle essentially devoid of MHC-I (superficial vastus lateralis)
      reached levels comparable to those in a muscle high in MHC-I (soleus).

PMID- 9018483
TI  - Fluid and electrolyte hormonal responses to exercise and acute plasma volume
      expansion.
AB  - To investigate the effect of acute graded increases in plasma volume (PV) on
      fluid and regulatory hormone levels, eight untrained men (peak aerobic power 45.2
      +/- 2.2 ml.kg-1.min-1) performed prolonged cycle exercise (46 +/- 4% maximal
      aerobic power on three occasions, namely, with no PV expansion (Con) and after
      14% (Low) and 21% (High) expansions, respectively. The exercise plasma levels of
      aldosterone (Aldo), arginine vasopressin (AVP), and atrial natriuretic peptide
      (ANP) were all altered by acute PV increases. A pronounced blunting (P < 0.05) of
      the Aldo response during exercise was observed, the magnitude of which was
      directly related to the amount of hypervolemia (Con < Low < High). At 120 min of
      exercise, Aldo concentrations were 660 +/- 71, 490 +/- 85, and 365 +/- 78 pg/ml
      for Con, Low, and High conditions, respectively. In contrast, the lower AVP and
      the higher ANP observed during exercise appeared to be due to the effect of PV
      expansion on resting concentrations. Because osmolality did not vary among
      conditions, the results indicate that PV represents an important primary stimulus
      in the response of Aldo to exercise. The lower exercise blood concentrations of
      both epinephrine and norepinephrine observed with PV expansion would suggest that
      a lower sympathetic drive may be implicated at least in the lower Aldo responses.

PMID- 9018484
TI  - Suppressive action of endogenous adenosine on ovine fetal nonshivering
      thermogenesis.
AB  - Nonshivering thermogenesis is not initiated when the fetal sheep is cooled in
      utero but appears to require the removal of an inhibitor of placental origin at
      birth. To test whether adenosine is such an inhibitor, we examined the effect of
      the adenosine antagonist theophylline on the initiation of nonshivering
      thermogenesis during sequential cooling, ventilation, and umbilical cord
      occlusion in utero. Theophylline (18 mg/kg bolus and 0.6 mg.kg-1.min-1
      thereafter) was infused for 90 min before and 90 min after cord occlusion.
      Theophylline enhanced the nonshivering thermogenic free fatty acid (FFA) and
      glycerol responses before cord occlusion, raising FFA concentrations 99% to 415
      +/- 60 mueq/l (P < 0.01) and glycerol levels 87% to 526 +/- 135 mumol/l (P <
      0.05). These FFA (P < 0.001) and glycerol (P < 0.05) concentrations were
      significantly greater than the corresponding period during the birth-simulation
      control. Umbilical cord occlusion did not alter FFA levels but induced a 41% rise
      in glycerol concentrations to 774 +/- 203 mumol/l (P < 0.05). The increases in
      nonshivering thermogenic indexes after the administration of the adenosine
      receptor antagonist suggest that the quiescent state of ovine fetal brown adipose
      tissue may result, in part, from the tonic inhibitory actions of adenosine and
      that a decrease in adenosine concentrations enhances nonshivering thermogenesis.
      However, the further rise after umbilical cord occlusion suggests that at least
      one other inhibitor of placental origin inhibits nonshivering thermogenesis
      before birth.

PMID- 9018485
TI  - Effect of expiratory flow limitation on respiratory mechanical impedance: a model
      study.
AB  - Large phasic variations of respiratory mechanical impedance (Zrs) have been
      observed during induced expiratory flow limitation (EFL) (M. Vassiliou, R.
      Peslin, C. Saunier, and C. Duvivier. Eur. Respir. J. 9: 779-786, 1996). To
      clarify the meaning of Zrs during EFL, we have measured from 5 to 30 Hz the input
      impedance (Zin) of mechanical analogues of the respiratory system, including flow
      limiting elements (FLE) made of easily collapsible rubber tubing. The pressures
      upstream (Pus) and downstream (Pds) from the FLE were controlled and
      systematically varied. Maximal flow (Vmax) increased linearly with Pus, was close
      to the value predicted from wave-speed theory, and was obtained for Pus-Pds of 4
      6 hPa. The real part of Zin started increasing abruptly with flow (V) > 85% Vmax
      and either further increased or suddenly decreased in the vicinity of Vmax. The
      imaginary part of Zin decreased markedly and suddenly above 95% Vmax. Similar
      variations of Zin during EFL were seen with an analogue that mimicked the changes
      of airway transmural pressure during breathing. After pressure and V measurements
      upstream and downstream from the FLE were combined, the latter was analyzed in
      terms of a serial (Zs) and a shunt (Zp) compartment. Zs was consistent with a
      large resistance and inertance, and Zp with a mainly elastic element having an
      elastance close to that of the tube walls. We conclude that Zrs data during EFL
      mainly reflect the properties of the FLE.

PMID- 9018486
TI  - Are basal metabolic rate prediction equations appropriate for female children and
      adolescents?
AB  - The basal metabolic rate (BMR), which accounts for 50-70% of total energy
      expenditure, is essential for estimation of patient and population energy needs.
      Numerous equations have been formulated for prediction of human BMR. Most
      equations in current use are based on measurements of Caucasians performed more
      than four decades ago. We evaluated 10 prediction equations commonly used for
      estimation of BMR in 76 Caucasian and 42 African-American girls between 8 and 17
      yr of age against BMR measured by whole-body calorimetry. The majority of the
      prediction equations (9 of 10) overestimated BMR by 60 +/- 46 kcal/day (range, 15
      176 kcal/day). This overestimation was found to be significantly greater (P <
      0.05) for African-American (77 +/- 17 kcal/day) than for Caucasians (25 +/- 17
      kcal/day) in six equations, controlling for age, weight, and sexual maturity. We
      conclude that ethnicity is an important factor in estimation of the BMR and that
      the current prediction equations are not appropriate for accurate estimation of
      the BMR of individual female children and adolescents.

PMID- 9018487
TI  - Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal
      muscle.
AB  - Nitric oxide (NO) is a pluripotent molecule that can be secreted by skeletal
      muscle through the activity of the neuronal constitutive isoform of NO synthase.
      To determine whether skeletal muscle and diaphragm might also express the
      macrophage-inducible form of NO synthase (iNOS) during provocative states, we
      examined tissue from mice at serial times after intravenous administration of
      Escherichia coli endotoxin. In these studies, iNOS mRNA was strongly expressed in
      the diaphragm and skeletal muscle of mice 4 h after intravenous endotoxin and was
      significantly diminished by 8 h after challenge. Induction of iNOS mRNA was
      followed by expression of iNOS immunoreactive protein on Western immunoblots.
      Increased iNOS activity was demonstrated by conversion of arginine to citrulline.
      Immunochemical analysis of diaphragmatic explants exposed to endotoxin in vitro
      revealed specific iNOS staining in myocytes, in addition to macrophages and
      endothelium. These results may be important in understanding the pathogenesis of
      respiratory pump failure during septic shock, as well as skeletal muscle injury
      during inflammation or metabolic stress.

PMID- 9018488
TI  - Noxious stimuli do not determine reflex cardiorespiratory effects in anesthetized
      rabbits.
AB  - The main purpose of this study is to examine whether the stimulation of an
      exclusively pain-sensing receptive field (dental pulp) could determine
      cardiorespiratory effects in animals in which the cortical integration of the
      peripheral information is abolished by deep anesthesia. In 15 anesthetized (alpha
      chloralose and urethan) rabbits, low (3-Hz)- and high-frequency (100-Hz)
      electrical dental pulp stimulation was performed. Because this stimulation caused
      dynamic and static reflex contractions of the digastric muscles leading to jaw
      opening jaw-opening reflex (JOR); an indirect sign of algoceptive fiber
      activation], experimentally induced direct dynamic and static contractions of the
      digastric muscle were also performed. The low- and high-frequency stimulation of
      the dental pulp determined cardiovascular [systolic arterial pressure (SAP): 
      21.7 +/- 4.6 and 10.8 +/- 4.7 mmHg, respectively] and respiratory [pulmonary
      ventilation (VE): 145.1 +/- 44.9 and 109.3 +/- 28.4 ml/min, respectively] reflex
      responses similar to those observed during experimentally induced dynamic (SAP: 
      17.5 +/- 4.2 mmHg; VE: 228.0 +/- 58.5 ml/min) and static (SAP: 5.8 +/- 1.5 mmHg;
      VE: 148.0 +/- 75.3 ml/min) muscular contractions. The elimination of digastric
      muscular contraction (JOR) obtained by muscular paralysis did away with the
      cardiovascular changes induced by dental pulp stimulation, the effectiveness of
      which in stimulating dental pulp receptors has been shown by recording trigeminal
      evoked potentials in six additional rabbits. The main conclusion was that, in
      deeply anesthetized animals, an algesic stimulus is unable to determine
      cardiorespiratory effects, which appear to be exclusively linked to the
      stimulation of ergoreceptors induced by muscular contraction.

PMID- 9018489
TI  - Effect of hypoxia on abdominal motor unit activities in spontaneously breathing
      cats.
AB  - These experiments were designed to examine the behavior of external oblique motor
      units in spontaneously breathing cats during hypoxia and to estimate the
      contribution of recruitment and rate coding to changes in the integrated external
      oblique electromyogram (iEMG). Motor unit activities in the external oblique
      muscle were identified while the cats expired against a positive end-expiratory
      pressure (PEEP) of 1-2.5 cmH2O. After localization of unit activity, PEEP was
      removed, and recordings were made continuously for 3-4 min during hyperoxia,
      normoxia, and hypoxia. A total of 35 single motor unit activities were recorded
      from 10 cats. At each level of fractional concentration of end-tidal O2, the
      motor unit activity was characterized by an abrupt increase in mean discharge
      frequency, at approximately 30% of expiratory time, which then continued to
      increase gradually or remained constant before declining abruptly at the end of
      expiration. The transition from hyperoxia to normoxia and hypoxia was accompanied
      by an increase in the number of active motor units (16 of 35, 20 of 35, and 29 of
      35, respectively) and by an increase in the mean discharge frequency of those
      units active during hyperoxia. The changes in motor unit activity recorded during
      hypoxia were accompanied by a significant increase in the average peak amplitude
      of the abdominal iEMG. Linear regression analysis revealed that motor unit rate
      coding was responsible for close to 60% of the increase in peak iEMG amplitude.
      The changes in abdominal motor unit activity and the external oblique iEMG that
      occurred during hypoxia were abolished if the arterial PCO2 was allowed to fall.
      We conclude that external oblique motor units are activated during the latter two
      thirds of expiration and that rate coding and recruitment contribute almost
      equally to the increase in expiratory muscle activity that occurs with hypoxia.
      In addition, the excitation of abdominal motor units during hypoxia is critically
      dependent on changes in CO2 and/or tidal volume.

PMID- 9018490
TI  - Functional role and structure of the scalene: an accessory inspiratory muscle in
      hamster.
AB  - Although the scalene muscle (Sca) is a primary inspiratory muscle in humans, its
      respiratory function in other species is less clear. The electromyographic (EMG)
      activity of the Sca was studied during resting ventilation (eupnea) in both the
      awake and anesthetized hamster and after a variety of respiratory challenges in
      the anesthetized animal. The EMG activities of the medial Sca and the costal
      diaphragm were compared. The medial Sca, the major component of the Sca,
      originates from cervical transverse processes 2 to 5 and inserts primarily onto
      rib 4, with a small segment onto rib 3. In both the anesthetized and awake
      animal, the Sca was always silent during quiet breathing. With CO2-stimulated
      hyperpnea, the Sca was always recruited during inspiration in phase with the
      diaphragm. Active recruitment of the Sca was also observed after resistive
      loading and total airway occlusion. After ipsilateral phrenicotomy, the Sca was
      persistently recruited during eupnea. The specificity of the EMG signals was
      tested both by excluding cross contamination from other rib cage muscles and by
      selective denervation studies. Muscle spindles were identified in the medial Sca
      histochemically, suggesting that the respiratory activity of the Sca can also be
      modulated by changes in muscle length and/or load. These results indicate that
      the Sca functions as an accessory inspiratory muscle in the hamster and may play
      an important role in conditions of chronic load.

PMID- 9018491
TI  - Influence of diet and exercise on skeletal muscle and visceral adipose tissue in
      men.
AB  - The effects of diet only (DO) and diet combined with either aerobic (DA) or
      resistance (DR) exercise on subcutaneous adipose tissue (SAT), visceral adipose
      tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in
      33 obese men (DO, n = 11; DA, n = 11; DR, n = 11). All tissues were measured by
      using a whole body multislice magnetic resonance imaging (MRI) model. Within each
      group, significant reductions were observed for body weight, SAT, and VAT (P <
      0.05). The reductions in body weight (approximately 10%) and SAT (approximately
      25%) and VAT volume (approximately 35%) were not different between groups (P >
      0.05). For all treatments, the relative reduction in VAT was greater than in SAT
      (P < 0.05). For the DA and DR groups only, the reduction in abdominal SAT
      (approximately 27%) was greater (P < 0.05) than that observed for the gluteal
      femoral region (approximately 20%). Conversely, the reduction in VAT was uniform
      throughout the abdomen regardless of treatment (P > 0.05). MRI-LT and MRI-SM
      decreased both in the upper and lower body regions for the DO group alone (P <
      0.05). Peak O2 uptake (liters) was significantly improved (approximately 14%) in
      the DA group as was muscular strength (approximately 20%) in the DR group (P <
      0.01). These findings indicate that DA and DR result in a greater preservation of
      MRI-SM, mobilization of SAT from the abdominal region, by comparison with the
      gluteal-femoral region, and improved functional capacity when compared with DO in
      obese men.

PMID- 9018492
TI  - Nitric oxide decreases lung injury after intestinal ischemia.
AB  - After injury to a primary organ, mediators are released into the circulation and
      may initiate inflammation of remote organs. We hypothesized that the local
      production of nitric oxide (NO) may act to limit the spread of inflammation to
      secondarily targeted organs. In anesthetized rats, 30 min of intestinal ischemia
      followed by 2 h of reperfusion (I/R) did not increase lung albumin leak. However,
      after treatment with NG-nitro-L-arginine methyl ester (L-NAME), intestinal I/R
      led to increased lung leak, suggesting a protective effect of endogenous NO. The
      site of action of NO appeared to be the lung and not the gut because 1) after
      treatment with L-NAME, local delivery of NO to the lung by inhalation abolished
      the increase in intestinal I/R-induced lung leak; 2) L-NAME had no effect on
      epithelial permeability (51Cr-labeled EDTA clearance) of reperfused small bowel;
      and 3) after treatment with L-NAME, local delivery of NO to the gut by luminal
      perfusion did not improve epithelial permeability of reperfused intestines.
      Furthermore, L-NAME increased, and inhaled NO decreased, the density of lung
      neutrophils in rats subjected to intestinal I/R, and treatment with the selectin
      antagonist fucoidan abolished L-NAME-induced lung leak in rats subjected to
      intestinal I/R. We conclude that endogenous lung NO limits secondary lung injury
      after intestinal I/R by decreasing pulmonary neutrophil retention.

PMID- 9018493
TI  - Effect of furosemide on hyperpnea-induced airway obstruction, injury, and
      microvascular leakage.
AB  - Furosemide attenuates hyperpnea-induced airway obstruction (HIAO) in asthmatic
      subjects via unknown mechanism(s). We studied the effect of furosemide on dry air
      induced bronchoconstriction, mucosal injury, and bronchovascular
      hyperpermeability in a canine model of exercise-induced asthma. Peripheral airway
      resistance (Rp) was recorded before and after a 2-min dry-air challenge (DAC) at
      2,000 ml/min. After pretreatment with aerosolized saline containing 0.75%
      dimethyl sulfoxide, DAC increased Rp 72 +/- 11% (SE, n = 7) above baseline;
      aerosolized furosemide (10(-3) M) reduced this response by approximately 50 +/-
      6% (P < 0.01). To assess bronchovascular permeability, colloidal carbon was
      injected (1 ml/kg i.v.) 1 min before DAC, and after 1 h, the vehicle- and
      furosemide-treated airways were prepared for morphometric analysis. Light
      microscopy confirmed previous studies showing that DAC damaged the airway
      epithelium and enhanced bronchovascular permeability. Furosemide did not inhibit
      dry air-induced mucosal injury or bronchovascular hyperpermeability and in fact
      tended to increase airway damage and vascular leakage. This positive trend toward
      enhanced bronchovascular permeability in DAC canine peripheral airways is
      consistent with the hypothesis that furosemide inhibits HIAO in part by enhancing
      microvascular leakage and thus counterbalancing the evaporative water loss that
      occurs during hyperpnea.

PMID- 9018494
TI  - Membranous bronchioles and connective tissue network of normal and emphysematous
      lungs.
AB  - Three-dimensional reconstructions of the septal system of normal human lungs
      revealed that airways course within the interlobular septa, i.e., between the two
      blades formed by the peripheral boundaries of adjacent lobuli of whatever order,
      and enter the supplied pulmonary unit at its side. This is not in keeping with
      the classic view of a peripheral airway in the center of a lung unit and
      submitted to radial traction by attached alveolar septa. The basic design of the
      lung fibrous scaffold appears to be in conformity with the laws of fractal
      geometry. Similar reconstructions in centrilobular emphysema disclosed
      tortuosities of both intra-acinar and interlobular septa, with consequent
      distortions of the corresponding intraseptal bronchioles and collapse of lung
      units of different sizes. It is suggested that in centrilobular emphysema
      competition for space, besides intrinsic airways narrowing because of
      inflammation and loss of elastic recoil, is a cause of flow limitation.

PMID- 9018495
TI  - Endothelin blockade augments pulmonary vasodilation in the ovine fetus.
AB  - The physiological role of endothelin-1 (ET-1) in regulation of vascular tone in
      the perinatal lung is controversial. Recent studies suggest that ET-1 contributes
      to high basal pulmonary vascular resistance in the normal fetus, but its role in
      the modulation of pulmonary vascular tone remains uncertain. We hypothesized that
      high ET-1 activity opposes the vasodilator response to some physiological stimuli
      such as increased pressure. To test the hypothesis that ET-1 modulates fetal
      pulmonary vascular responses to acute and prolonged physiological stimuli, we
      performed a series of experiments in the late-gestation ovine fetus. We studied
      the hemodynamic effects of two ET-1 antagonists, BQ-123 (a selective ETA-receptor
      antagonist) and phosphoramidon (a nonselective ET-1-converting enzyme inhibitor)
      during mechanical increases in pressure due to partial ductus arteriosus
      compression in chronically prepared late-gestation fetal lambs. In control
      studies, partial ductus arteriosus compression decreased the ratio of pulmonary
      arterial pressure to pulmonary artery flow in the left lung 34 +/- 6% from
      baseline. Intrapulmonary infusions of BQ-123 (0.5 microgram/min for 10 min; 0.025
      microgram/min for 2 h) or phosphoramidon (1.0 mg/min for 10 min) augmented the
      peak vasodilator response during ductus arteriosus compression (52 +/- 3 and 49
      +/- 6% from baseline, respectively, P < 0.05 vs. control). In addition, unlike
      the transient vasodilator response to ductus arteriosus compression in control
      studies, ET-1 blockade with BQ-123 or phosphoramidon prolonged the increase in
      flow caused by ductus arteriosus compression. In summary, ETA-receptor blockade
      and ET-1-converting enzyme inhibition augment and prolong fetal pulmonary
      vasodilation during partial compression of the ductus arteriosus. We conclude
      that ET-1 activity modulates acute and prolonged responses of the fetal pulmonary
      circulation to changes in vascular pressure. We speculate that ET-1 contributes
      to regulation and maintenance of high pulmonary vascular resistance in the normal
      ovine fetal lung.

PMID- 9018496
TI  - Lactate and epinephrine during exercise in altitude natives.
AB  - We tested the hypothesis that the reported low blood lactate accumulation ([La])
      during exercise in altitude-native humans is refractory to hypoxianormoxia
      transitions by investigating whether acute changes in inspired O2 fraction (FIo2)
      affect the [La] vs. power output (W) relationship or, alternatively, as reported
      for lowlanders, whether changes in [La] vs. W on changes in FIo2 are related to
      changes in blood epinephrine concentration ([Epi]). Altitude natives [n = 8, age
      24 +/- 1 (SE) yr, body mass 62 +/- 3 kg, height 167 +/- 2 cm] in La Paz, Bolivia
      (3,600 m) performed incremental exercise with two legs and one leg in chronic
      hypoxia and acute normoxia (AN). Submaximal one- and two-leg O2 uptake (Vo2) vs.
      W relationships were not altered by FIo2. AN increased two-leg peak Vo2 by 10%
      and peak W by 7%. AN paradoxically decreased one-leg peak Vo2 by 7%, whereas peak
      W remained the same. The [La] vs. W relationships were similar to those reported
      in unacclimatized lowlanders. There was a shift to the right on AN, and maximum
      [La] was reduced by 7 and 8% for one- and two-leg exercises, respectively. [Epi]
      and [La] were tightly related (mean r = 0.81) independently of FIo2. Thus
      normoxia attenuated the increment in both [La] and [Epi] as a function of W,
      whereas the correlation between [La] and [Epi] was unaffected. These data suggest
      loose linkage of glycolysis to oxidative phosphorylation under influence from
      [Epi]. In conclusion, high-altitude natives appear to be not fundamentally
      different from lowlanders with regard to the effect of acute changes in FIo2 on
      [La] during exercise.

PMID- 9018497
TI  - Delay time adjustments to minimize errors in breath-by-breath measurement of Vo2
      during exercise.
AB  - If the delay time between gas concentration and flow signals is not adequately
      corrected during breath-by-breath analysis of expired gas, an error in
      calculation of oxygen consumption (Vo2) will result. To examine the frequency and
      delay time dependences of errors in Vo2 measurement, six healthy men exercised at
      100, 200, and 250 W on a cycle ergometer while breath-by-breath assessment of Vo2
      was made simultaneously with collection of expired air. Subjects breathed first
      at normal rates (15-30 breaths/min) and then at 70 breaths/min. Each subject
      performed each level of exercise twice by using erroneous values for the delay
      time between gas concentration and flow signals. At normal breathing frequencies,
      errors in Vo2 measurement were +/- 10% over the full range of delay times used,
      and the errors were not tightly correlated with variations in delay times from
      optimum. However, at 70 breaths/min, errors approached +/- 30% as the variations
      in delay times deviated +/- 0.1 s from the optimal, and the errors were highly
      correlated with the variations in delay times. We conclude that there is greater
      potential for errors in Vo2 measurement with incorrect delay time at higher
      breathing frequencies. These findings suggest that the optimal delay time for
      breath-by-breath systems should be adjusted by using high breathing frequencies.

PMID- 9018498
TI  - Effects of hypoxic hypoxia on O2 uptake and heart rate kinetics during heavy
      exercise.
AB  - It is unclear whether hypoxia alters the kinetics of O2 uptake (VO2) during heavy
      exercise [above the lactic acidosis threshold (LAT)] and how these alterations
      might be linked to the rise in blood lactate. Eight healthy volunteers performed
      transitions from unloaded cycling to the same absolute heavy work rate for 8 min
      while breathing one of three inspired O2 concentrations: 21% (room air), 15%
      (mild hypoxia), and 12% (moderate hypoxia). Breathing 12% O2 slowed the time
      constant but did not affect the amplitude of the primary rise in VO2 (period of
      first 2-3 min of exercise) and had no significant effect on either the time
      constant or the amplitude of the slow VO2 component (beginning 2-3 min into
      exercise). Baseline heart rate was elevated in proportion to the severity of the
      hypoxia, but the amplitude and kinetics of increase during exercise and in
      recovery were unaffected by level of inspired O2. We conclude that the
      predominant effect of hypoxia during heavy exercise is on the early energetics as
      a slowed time constant for VO2 and an additional anaerobic contribution. However,
      the sum total of the processes representing the slow component of VO2 is
      unaffected.

PMID- 9018499
TI  - The relationships among IGF-1, DNA content, and protein accumulation during
      skeletal muscle hypertrophy.
AB  - Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on
      skeletal muscle cells. This study examined the time course of muscle hypertrophy
      and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7,
      14, and 28 days after surgical removal of synergistic muscles of both normal and
      hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass,
      myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P
      < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of
      overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases
      in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the
      overloaded Plant increased in both groups. There was a strong positive
      relationship between IGF-1 peptide and DNA content in the overloaded Plant from
      both groups. These results indicate that 1) the muscles from rats with both
      normal and severely depressed systemic levels of IGF-1 respond to functional
      overload with an increase in local IGF-1 expression and 2) this elevated IGF-1
      may be contributing to the hypertrophy response, possibly via the mobilization of
      satellite cells to provide increases in muscle DNA.

PMID- 9018500
TI  - Surfactant inhibition by plasma: gestational age and surfactant treatment effects
      in preterm lambs.
AB  - The preterm infant with respiratory distress syndrome has edematous lungs and
      small amounts of surfactant that do not function normally. We reported that
      surfactant recovered from preterm lambs after surfactant treatment can have
      decreased sensitivity to inhibition of surface tension by plasma. We asked
      whether this augmented resistance to inhibition was dependent on lung development
      (gestational age) by testing sensitivity to plasma inhibition of 1) endogenous
      surfactant from preterm lambs and 2) surfactant from preterm lambs after
      treatment with an organic solvent-extracted natural sheep surfactant. Surfactant
      recovered after surfactant treatment of 121- or 128-days-gestation lambs had the
      same sensitivity to plasma inhibition as did the surfactant used to treat the
      lambs. Surfactant recovered from 134-days-gestation lambs had decreased
      sensitivity to inhibition. Lung maturation is a variable influencing surfactant
      inhibition by plasma.

PMID- 9018501
TI  - Enhancement of intestinal water absorption and sodium transport by glycerol in
      rats.
AB  - Glycerol (Gly) is a hydrophilic, absorbable, and energy-rich solute that could
      make water absorption more efficient. We investigated the use of Gly in a high
      energy beverage containing corn syrup (CS) by using a small intestine perfusion
      procedure in the rat, an approach shown earlier to provide good preclinical
      information. The effectiveness of several formulations with Gly and CS was
      compared with commercial products and to experimental formulas where Gly
      substituted for glucose (Glc). The CS-Gly combination was more effective than
      preparations on the market containing sucrose and Glc-fructose syrups (G-P and G
      L, respectively) in maintaining a net water absorption balance in the test
      jejunal segment [CS-Gly = 0.21 +/- 0.226, G-L = -1.516 +/- 0.467, and G-P = 
      0.299 +/- 0.106 (SE) microliter.min-1.cm-1 (P = 0.0113)] and in reducing sodium
      release into the lumen [CS-Gly = -133.2 +/- 16.2, G-L = -226.7 +/- 25.2, and G-P
      = -245.6 +/- 23.4 nmol.min-1.cm-1 (P = 0.0022)]. In other preparations, at equal
      CS concentrations (60 and 80 g/l, respectively), Gly clearly improved net water
      absorption over a comparable Glc-containing product [CS60-Gly = 0.422 +/- 0.136
      and CS80-Gly = 0.666 +/- 0.378 vs. CS60-Glc = -0.282 +/- 0.200 and CS80-Glc = 
      1.046 +/- 0.480 microliters.min-1.cm-1 (P = 0.0019)]. On the basis of the data of
      this rat intestine perfusion model, Gly could be a useful ingredient in energy
      rich beverages and might enhance fluid absorption in humans.

PMID- 9018502
TI  - Arginine-induced pancreatic hormone secretion during exercise in rats.
AB  - The aim of the present investigation was to 1) determine whether arginine-induced
      pancreatic hormone secretion can be modified during an exercise bout, and 2)
      verify whether the sectioning of the hepatic branch of the vagus nerve can alter
      the arginine-induced insulin and glucagon secretion during exercise in rats. To
      this end, we studied the effects of an intraperitoneal injection of arginine (1
      g/kg body mass) during an exercise bout (30 min, 26 m/min, 0% grade) on the
      pancreatic hormone responses. These effects were determined in one group of sham
      operated exercising rats and compared with three control groups: one group of
      resting rats, one group of saline-injected exercising rats, and one group of
      hepatic-vagotomized exercising rats. Five minutes after the injection of
      arginine, significant (P < 0.05) increases in insulin, glucagon, and C-peptide
      concentrations were observed in exercising as well as in resting rats. These
      responses were not, however, altered by the hepatic vagotomy and/or by the
      exercise bout. It is concluded that arginine is a potent stimulus of pancreatic
      hormone secretion during exercise, even though the sympathoadrenal system is
      activated. These results also indicate that a hepatic vagotomy does not seem to
      influence arginine-induced hormonal pancreatic responses and question the role of
      the putative hepatic arginoreceptors in the control of the pancreatic hormone
      secretion during exercise.

PMID- 9018503
TI  - Prostaglandins E2 and I2 cause greater relaxations in pulmonary veins than in
      arteries of newborn lambs.
AB  - Prostaglandins E2 (PGE2) and I2 (PGI2) are important vasoactive mediators in
      pulmonary vessels. The present study was designed to determine whether the
      responses of pulmonary arteries to these prostanoids are different from those of
      veins in newborn lambs. Fourth-generation pulmonary arterial and venous rings
      without endothelium were suspended in organ chambers filled with modified Krebs
      Ringer bicarbonate solution (95% O2-5% CO2, 37 degrees C), and their isometric
      force was measured. During contraction with endothelin-1 or U-46619 (indomethacin
      was present to eliminate the possible involvement of endogenous cyclooxygenase
      products), PGE2, PGI2, and carbacyclin (a stable analogue of PGI2) induced
      greater relaxations in veins than in arteries. In both vessel types, relaxations
      induced by PGE2 were greater than those induced by PGI2 or carbacyclin.
      Forskolin, an activator of adenylate cyclase, also induced greater relaxation of
      veins than of arteries. Relaxation induced by 8-bromoadenosine 3',5' -cyclic
      monophosphate, an analogue of adenosine 3',5' -cyclic monophosphate (cAMP), was
      comparable in both vessel types. Radioimmunoassay revealed that the basal and
      calcium ionophore A-23187-induced releases of PGE2 or 6-ketoprostaglandin F1
      alpha (the stable breakdown product of PGI2) were similar between arteries and
      veins. Measurement of cAMP (in the presence of isobutylmethylxanthine) showed
      that PGE2 and forskolin induced greater increase in cAMP in veins than in
      arteries. Our results demonstrate that PGE2 and PGI2 are more potent vasodilators
      in pulmonary veins than in arteries in newborn lambs. A difference in the
      activity of adenylate cyclase may contribute to the differential responses to
      PGE2 and PGI2 between pulmonary arteries and veins. Furthermore, PGE2 appears
      play an more important role than does PGI2 in modulating pulmonary vascular tone
      of newborn lambs.

PMID- 9018505
TI  - Appropriate thermal manipulations eliminate tremors in rats recovering from
      halothane anesthesia.
AB  - Tremors are common in mammals emerging from anesthesia. To determine whether
      appropriate thermal manipulations immediately before emergence from anesthesia
      are sufficient to eliminate these tremors, electroencephalographic (EEG) and
      electromyographic (EMG) activities, hypothalamic temperature (Thy), and O2
      consumption were monitored in 12 rats recovering from halothane anesthesia under
      three thermal regimes. EEG and EMG activities were recorded throughout anesthesia
      and served as feedback signals for controlling anesthetic depth. During
      anesthesia, Thy was either 1) allowed to fall to 32-34 degrees C, 2) maintained
      at 37-39 degrees C, or 3) allowed to fall to 32-34 degrees C and then raised to
      37-39 degrees C. When hypothermic on emergence from anesthesia, all of the
      animals exhibited postanesthetic tremors that persisted until Thy values returned
      to normothermia. None of the animals expressed postanesthetic tremors when
      normothermic on emergence from anesthesia. In addition, the time between
      emergence from anesthesia (as determined by EEG/EMG parameters) and the
      initiation of coordinated motor activities was significantly decreased in the
      normothermic animals.

PMID- 9018504
TI  - Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus
      muscle fibers.
AB  - The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos
      2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and
      single muscle fibers were determined. On the basis of electrophoretic analyses,
      there was a de novo synthesis of type IIx MHC but no change in either type I or
      IIa MHC isoform proportions after either SF or HS compared with controls. The
      percentage of fibers containing only type I MHC decreased by 26 and 23%, and the
      percentage of fibers with multiple MHCs increased from 6% in controls to 32% in
      HS and 34% in SF rats. Type IIx MHC was always found in combination with another
      MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively.
      These data suggest that the expression of the normal complement of MHC isoforms
      in the adult rat soleus muscle is dependent, in part, on normal weight bearing
      and that the absence of weight bearing induces a shift toward type IIx MHC
      protein expression in the preexisting type I and IIa fibers of the soleus.

PMID- 9018506
TI  - Decreased contraction economy in mouse EDL muscle injured by eccentric
      contractions.
AB  - The objective of this study was to find out whether basal and/or active energy
      metabolism are altered in isolated mouse extensor digitorum longus muscle injured
      by eccentric (Ecc) contractions. Measurements of basal O2 consumption and
      isometric tetanus O2 recovery cost were made at 25 degrees C on muscles that had
      done either 10 Ecc, 10 isometric (Iso), or no contractions (No). In parallel
      experiments, rates of lactate and pyruvate production were measured to estimate
      the anaerobic contribution. Basal O2 consumption was unaffected by the type of
      protocol performed (P = 0.07). However, the tetanus O2 cost per force-time
      integral was elevated by 30-36% for the Ecc protocol muscles over that for the
      Iso and No protocol muscles. When including the increased lactate production by
      the Ecc protocol muscles, the total energetic cost per force-time integral was
      53% higher than that for the Iso protocol muscles [2.35 +/- 0.17 vs. 1.54 +/-
      0.18 mumol O2/(N.m.s)]. The decreased economy was attributed to two factors.
      First, in skinned fibers isolated from the injured muscles, the ratio of maximal
      actomyosin adenosinetriphosphatase activity to force production was up by 37.5%,
      suggesting uncoupling of ATP hydrolysis from force production. Second, increased
      reliance on anaerobic metabolism along with the fluorescent microscopic study of
      mitochondrial membrane potential and histochemical study of ATP synthase
      suggested an uncoupling of oxidative phosphorylation in the injured muscles.

PMID- 9018507
TI  - Heat stroke: opioid-mediated mechanisms.
AB  - In our previous study in guinea pigs, intensive and prolonged intraperitoneal
      heating (IPH) caused heat stroke characterized by high mortality and accompanied
      by two paradoxical phenomena: ear skin vasoconstriction at a high body
      temperature (Tb) (hyperthermia-induced vasoconstriction) and a post-IPH Tb fall
      at an ambient temperature (Ta) below thermoneutrality (hyperthermia-induced
      hypothermia). In this study, we tested the hypothesis that the mechanisms of the
      two phenomena involve endogenous opioid agonists. Experiments were conducted in
      24 unanesthetized, lightly restrained guinea pigs, each chronically implanted
      with an intraperitoneal thermode and intrahypothalamic thermocouple. The
      thermoregulatory effects of a wide-spectrum opioid-receptor antagonist,
      naltrexone (NTX; 50 or 0 mumol/kg sc), were studied in IPH-induced heat stroke
      and under normal conditions. IPH was accomplished by perfusing (50 ml/min; 80
      min) water (45 degrees C) through the thermode. Ta was maintained at
      approximately 24 degrees C. Skin vasodilation occurred at the onset of IPH but
      later changed to vasoconstriction despite high Tb and continuing IPH. IPH-induced
      hyperthermia (1.8 +/- 0.1 degrees C) was followed by a post-IPH Tb fall (-5.1 +/-
      0.7 degree C; calculated for the survivors only). The 48-h mortality rate was
      50%. NTX prevented the hyperthermia-induced vasoconstriction and attenuated the
      hyperthermia-induced hypothermia (-1.8 +/- 0.4 degree C). None of the NTX-treated
      animals died. The effects of NTX on Tb regulation under normal conditions were
      minor. These results indicate that the phenomena of both hyperthermia-induced
      vasoconstriction and hyperthermia-induced hypothermia are opioid dependent. The
      latter is speculated to reflect opioid-mediated inhibition of metabolism; the
      former is thought to result from opioid-induced hemodynamic alterations. Because
      both phenomena did not occur in the NTX-treated survivors, the skin
      vasoconstriction at high Tb and the posthyperthermia Tb fall may be viewed as
      markers of the severity of heat stroke. It is suggested that opioid antagonists
      may have therapeutic potential in heat-induced disorders.

PMID- 9018508
TI  - Muscular blood flow response to submaximal leg exercise in normal subjects and in
      patients with heart failure.
AB  - Blood flow to working skeletal muscle is usually reduced during exercise in
      patients with congestive heart failure. An intrinsic impairment of skeletal
      muscle vasodilatory capacity has been suspected as a mechanism of this muscle
      underperfusion during maximal exercise, but its role during submaximal exercise
      remains unclear. Therefore, we studied by transcutaneous Doppler ultrasonography
      the arterial blood flow in the common femoral artery at rest and during a
      submaximal bicycle exercise in 12 normal subjects and in 30 patients with heart
      failure. Leg blood flow was lower in patients than in control subjects at rest
      [0.29 +/- 0.14 (SD) vs. 0.45 +/- 0.14 l/min, P < 0.01], at absolute powers and at
      the same relative power (2.17 +/- 1.06 vs. 4.39 +/- 1.4 l/min, P < 0.001).
      Because mean arterial pressure was maintained, leg vascular resistance was higher
      in patients than in control subjects at rest (407 +/- 187 vs. 247 +/- 71 mmHg.l
      1.min, P < 0.01) and at the same relative power (73 +/- 49 vs. 31 +/- 13 mmHg.l
      1.min, P < 0.01) but not at absolute powers. Although the magnitude of increase
      in leg blood flow corrected for power was similar in both groups (31 +/- 10 vs.
      34 +/- 10 ml.min-1.W-1), the magnitude of decrease of leg vascular resistance
      corrected for power was higher in patients than in control subjects (5.9 +/- 3.3
      vs. 1.9 +/- 0.94 mmHg.l-1.min.W-1, P < 0.001). These results suggest that the
      ability of skeletal muscle vascular resistance to decrease is not impaired and
      that intrinsic vascular abnormalities do not limit vasodilator response to
      submaximal exercise in patients with heart failure.

PMID- 9018509
TI  - Segmental body composition assessed by bioelectrical impedance analysis and DEXA
      in humans.
AB  - The present study assessed the relative contribution of each body segment to
      whole body fat-free mass (FFM) and impedance and explored the use of segmental
      bioelectrical impedance analysis to estimate segmental tissue composition.
      Multiple frequencies of whole body and segmental impedances were measured in 51
      normal and overweight women. Segmental tissue composition was independently
      assessed by dual-energy X-ray absorptiometry. The sum of the segmental impedance
      values corresponded to the whole body value (100.5 +/- 1.9% at 50 kHz). The arms
      and legs contributed to 47.6 and 43.0%, respectively, of whole body impedance at
      50 kHz, whereas they represented only 10.6 and 34.8% of total FFM, as determined
      by dual-energy X-ray absorptiometry. The trunk averaged 10.0% of total impedance
      but represented 48.2% of FFM. For each segment, there was an excellent
      correlation between the specific impedance index (length2/impedance) and FFM (r =
      0.55, 0.62, and 0.64 for arm, trunk, and leg, respectively). The specific
      resistivity was in a similar range for the limbs (159 +/- 23 cm for the arm and
      193 +/- 39 cm for the leg at 50 kHz) but was higher for the trunk (457 +/- 71
      cm). This study shows the potential interest of segmental body composition by
      bioelectrical impedance analysis and provides specific segmental body composition
      equations for use in normal and overweight women.

PMID- 9018510
TI  - Ovine fetal adaptations to chronically reduced urine flow: preservation of
      amniotic fluid volume.
AB  - Adequate amniotic fluid (AF) volume is maintained by a balance of fetal fluid
      production (lung liquid and urine) and resorption (swallowing and intramembranous
      flow). Because fetal urine is the principle source of AF, alterations in urine
      flow and composition directly impact AF dynamics. Intra-amniotic 1-desamino-8-D
      arginine vasopressin (DDAVP) is rapidly absorbed into fetal plasma and induces a
      marked fetal urinary antidiuresis. To examine the effect of intra-amniotic- DDAVP
      induced fetal urinary responses on AF volume and composition, six chronically
      prepared ewes with singleton fetuses (gestation 128 +/- 2 days) were studied for
      72 h after a single intra-amniotic DDAVP (50-microgram) injection. After DDAVP,
      fetal urine osmolality significantly increased at 2 h (157 +/- 13 to 253 +/- 21
      mosmol/kg) and remained elevated at 72 h (400 +/- 13 mosmol/kg). Urinary sodium
      (33.0 +/- 4.5 to 117.2 +/- 9.7 meq/l) and chloride (26.0 +/- 2.8 to 92.4 +/- 8.1
      meq/l) concentrations similarly increased. AF osmolality increased (285 +/- 3 to
      299 +/- 4 mosmol/kg H2O), although there was no change in fetal plasma osmolality
      (294 +/- 2 mosmol/kg). Despite a 50% reduction in fetal urine flow (0.12 +/- 0.03
      to 0.05 +/- 0.02 ml.kg-1.min-1 at 2 h and 0.06 +/- 0.01 ml.kg-1.min-1 after 72
      h), AF volume did not change (693 +/- 226 to 679 +/- 214 ml). There were no
      changes in fetal arterial blood pressures, pH, PCO2, or PO2 after DDAVP. We
      conclude the following. 1) Intra-amniotic DDAVP injection induces a prolonged
      decrease in fetal urine flow and increases in urine and AF osmolalities. 2)
      Despite decreased urine flow, AF volume does not change. We speculate that, in
      response to DDAVP-induced fetal oliguria, reversed intramembranous flow (from
      isotonic fetal plasma to hypertonic AF) preserves AF volume.

PMID- 9018511
TI  - Pulmonary vasoconstrictor effects of prostacyclin in rats: potential role of
      thromboxane receptors.
AB  - Endogenous prostacyclin (PGI2; epoprostenol) is a potent endothelium-derived
      pulmonary vasodilator. However, the effects of exogenous PGI2 on isolated
      arteries could be either relaxant or contractile, depending on the species and
      organ studied. The present study investigated the distal pathways involved in the
      PGI2-induced contraction in rat intrapulmonary artery (PA) and relaxation in lamb
      PA. When vessels were precontracted with 30 mM K+, PGI2 (1 microM) induced
      relaxation in lamb PA but caused contraction in rat PA. Use of 30 mM K+,
      phenylephrine, serotonin, angiotensin II, or hypoxia to precontract the vessels
      did not alter the contractile effect of PGI2 in rat PA. Nevertheless, PGI2
      produced a mild relaxation in rat PA precontracted by U-46619, a thromboxane A2
      (TxA2)-receptor agonist, whereas the TxA2-receptor blocker SQ-29548 (0.1-0.5
      microM) abolished the contractile response in rat PA. These data suggest that
      PGI2-induced contraction is mediated by activation of TxA2 receptors. The PGI2
      induced modest relaxation in rat PA, which was only observed when TxA2 receptors
      were blocked by SQ-29548, suggests that the PGI2-mediated vasorelaxant pathway is
      diminished in these vessels. Simultaneous application of forskolin, an adenylate
      cyclase activator, and rolipram, a phosphodiesterase inhibitor, caused similar
      relaxation in both rat and lamb PA. This suggests that the adenosine 3',5'-cyclic
      monophosphate-dependent relaxing pathway is intact in rat PA and is comparable to
      that in lamb PA. On the basis of these data, we conclude that the pathways
      responsible for the paradoxical effects of PGI2 on rat and lamb PA are located
      upstream of the adenosine 3',5'-cyclic monophosphate-dependent relaxing pathway
      and that a paucity of PGI2 receptors in rat PA may be responsible.

PMID- 9018512
TI  - Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit.
AB  - The effects of Diazinon PLUS aerosol on the activities of rapidly adapting
      receptors (RARs) and slowly adapting receptors (SAR) of the airways were
      investigated in anesthetized rabbits. The effects on both the baseline activity
      and the responses to stimulation by increasing mean left atrial pressure were
      examined. Action potentials were recorded from the left cervical vagus nerve.
      Aerosols (particle size 3 microns) were generated by a Mini-HEART nebulizer. We
      observed that an aerosol of Diazinon PLUS (1:10 vol/vol dilution in normal
      saline) decreased the baseline RAR activity (n = 10) significantly (P < 0.05)
      from 209 +/- 77 to 120 +/- 40 impulses/min. In the post-Diazinon PLUS control
      period, the RAR activity recovered partially to 185 +/- 75 impulses/min and
      decreased significantly to 131 +/- 52 impulses/min (P < 0.05) after a second
      exposure of Diazinon PLUS (undiluted) aerosol. Aerosols of normal saline in the
      control state did not produce a significant change in the RAR activity. A group
      of SAR (n = 8) were examined under similar conditions, and it was found that only
      the exposure to Diazinon PLUS (undiluted) aerosol decreased the activity
      significantly (P < 0.05) from 1,536 +/- 206 to 1,367 +/- 182 impulses/min. The
      effect of Diazinon PLUS on the response to increasing mean left atrial pressure
      was examined in seven RARs. In the control state, RAR activity increased
      significantly (P < 0.05) during elevation of mean left atrial pressure. This
      response was abolished after exposure to Diazinon PLUS. These findings suggest
      that diazinon may interfere with airway defense mechanisms by reducing the
      activity of RARs.

PMID- 9018513
TI  - Pseudoephedrine is without ergogenic effects during prolonged exercise.
AB  - This study was designed to measure whether a single dose of 120 mg
      pseudoephedrine ingested 120 min before exercise influences performance during 1
      h of high-intensity exercise. The effects of exercise on urinary excretion of the
      drug were also studied. Ten healthy male cyclists were tested on two occasions,
      separated by at least 7 days, by using a randomly assigned, double-blind, placebo
      controlled, crossover design. Exercise performance was tested during a 40-km
      trial on a laboratory cycle ergometer, and skeletal muscle function was measured
      during isometric contractions. On a third occasion, subjects ingested 120 mg
      pseudoephedrine but did not exercise [control (C)]. Pseudoephedrine did not
      influence either time trial performance [drug (D) vs. placebo: 58.1 +/- 1.4 (SE)
      vs. 58.7 +/- 1.5 min] or isometric muscle function. Urinary pseudoephedrine
      concentrations were significantly increased 1 h after exercise (D vs. C: 114.3 +/
      27.2 vs. 35.4 +/- 13.1 micrograms/ml; P < 0.05). Peak plasma pseudoephedrine
      concentrations (P < 0.05) but not time taken to reach peak plasma concentrations
      or the area under the plasma pseudoephedrine concentration vs. time curve was
      significantly increased in the total group with exercise (D vs. C). In three
      subjects, plasma pseudoephedrine concentrations were not influenced by exercise.
      Only these subjects showed increased urinary pseudoephedrine excretion during
      exercise. We conclude that a single therapeutic dose of pseudoephedrine did not
      have a measurable ergogenic effect during high-intensity exercise of 1-h
      duration, but plasma drug concentrations and urinary excretion were altered by
      exercise. These findings have practical relevance to doping control regulations
      in international sporting competitions.

PMID- 9018514
TI  - Effect of topical upper airway anesthesia on apnea duration through the night in
      obstructive sleep apnea.
AB  - It has previously been reported that the duration of obstructive apneas increases
      from the beginning to the end of the night (M. Charbonneau, J. M. Marin, A. Olha,
      R. J. Kimoff, R. D. Levy, and M. Cosio. Chest 106: 1695-1701, 1994). The purpose
      of this study was to test the hypothesis that stimulation of upper airway (UA)
      sensory receptors during obstructed inspiratory efforts contributes to arousal
      and apnea termination and that a progressive attenuation of this mechanism
      through the night contributes to apnea lengthening. We studied seven patients
      (six men, one woman) with severe obstructive sleep apnea (apnea-hypopnea index =
      93 +/- 26 events/h) during two consecutive nights of polysomnographic monitoring.
      On one night (random order), we performed topical UA anesthesia with 0.2%
      tetracaine and on the control night, sham anesthesia. We measured apnea duration,
      esophageal pressure (Pes) during apneas, and apneic O2 desaturation. Consistent
      with previous findings, apnea duration, number of efforts per apnea, and peak Pes
      at end apnea increased from the beginning to the end of the control nights. UA
      anesthesia produced a significant increase in apnea duration at the beginning of
      the night but no change in apnea length at the end of the night. Peak Pes and the
      rate of increase in Pes during the anesthesia nights were greater than during
      control nights, but the rate of increase in Pes was similar for the beginning and
      end of the control and anesthesia nights. These findings suggest that UA sensory
      receptors play a role in mediating apnea termination at the beginning of the
      night but that the contribution of these receptors diminishes as the night
      progresses such that greater inspiratory efforts are required to trigger arousal,
      leading to apnea prolongation.

PMID- 9018515
TI  - Reproductive function in male endurance athletes: sperm analysis and hormonal
      profile.
AB  - The purpose of this investigation was to study the effects of endurance exercise
      on male reproductive function (sex hormones and seminograms). Professional
      cyclists [n = 12; mean age 24 +/- 2 (SD) yr], elite triathletes (n = 9; 26 +/- 3
      yr), recreational marathon runners (n = 10; 32 +/- 6 yr), and sedentary subjects
      (control group; n = 9; 30 +/- 4 yr) were selected as subjects. for each group,
      the following parameters were measured three times during the sports season
      (training period: winter; competition period: spring; resting period: fall):
      percentage of body fat, hormonal profile (resting levels of follicle-stimulating
      hormone, luteinizing hormone, total and free testosterone, and cortisol), and
      seminograms (quantitative parameters sperm volume and sperm count; qualitative
      parameters: sperm motality and morphology). The following comparisons were made
      in the measured parameters: 1) within groups (longitudinal design) and 2) between
      groups in each of the three periods (cross-sectional design) and over time (mixed
      design). In addition, both the volume and the intensity of training of each
      subject during the season (except for the control group) were quantified. Despite
      significant differences in training characteristics and in body fat percent, in
      general no significant differences (P > 0.05) were found in hormonal profiles or
      in semen characteristics between or within groups. A lower sperm motility (46.2
      +/- 19.5%), however, was observed in the cyclists during the competition period
      when compared either with the other groups during this same period (P < 0.05) or
      with themselves during the other two periods of study (P < 0.01). In any case,
      the later phenomenon was attributed to physical factors associated with cycling,
      such as mechanical trauma to the testis and/or increased gonadal temperature. In
      conclusion, our findings suggest that endurance exercise does not adversely
      affect the hypothalamic-pituitary-testis axis.

PMID- 9018516
TI  - Greater airway narrowing in immature than in mature rabbits during methacholine
      challenge.
AB  - It has been demonstrated that methacholine (MCh) challenge produces a greater
      increase in lung resistance in immature than in mature rabbits (R. S. Tepper, X.
      Shen, E. Bakan, and S. J. Gunst. J. Appl. Physiol. 79: 1190-1198, 1995). To
      determine whether this maturational difference in the response to MCh was
      primarily related to changes in airway resistance (Raw) or changes in tissue
      resistance, we assessed airway narrowing in 1-, 2-, and 6-mo-old rabbits during
      intravenous MCh challenge (0.01-5.0 mg/kg). Airway narrowing was determined from
      measurements of Raw in vivo and from morphometric measurements on lung sections
      obtained after rapidly freezing the lung after the MCh challenge. The fold
      increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6
      mo-old animals. Similarly, the degree of airway narrowing assessed
      morphometrically was significantly greater for 1- and 2-mo-old animals than for 6
      mo-old animals. The fold increase in Raw was highly correlated with the degree of
      airway narrowing assessed morphometrically (r2 = 0.82, P < 0.001). We conclude
      that the maturational difference in the effect of MCh on lung resistance is
      primarily caused by greater airway narrowing in the immature rabbits.

PMID- 9018517
TI  - Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike
      performance over 100 km.
AB  - This study was undertaken to determine the effects of ingesting either glucose
      (trial G) or glucose plus branched-chain amino acids (BCAA: trial B), compared
      with placebo (trial P), during prolonged exercise. Nine well-trained cyclists
      with a maximal oxygen uptake of 63.1 +/- 1.5 ml O2. min-1.kg-1 performed three
      laboratory trials consisting of 100 km of cycling separated by 7 days between
      each trial. During these trials, the subjects were encouraged to complete the 100
      km as fast as possible on their own bicycles connected to a magnetic brake. No
      differences in performance times were observed between the three trials (160.1 +/
      4.1, 157.2 +/- 4.5, and 159.8 +/- 3.7 min, respectively). In trial B, plasma
      BCAA levels increased from 339 +/- 28 microM at rest to 1,026 +/- 62 microM after
      exercise (P < 0.01). Plasma ammonia concentrations increased during the entire
      exercise period for all three trials and were significantly higher in trial B
      compared with trials G and P (P < 0.05). The respiratory exchange ratio was
      similar in the three trials during the first 90 min of exercise; thereafter, it
      tended to drop more in trial P than in trials G and B. These data suggest that
      neither glucose nor glucose plus BCAA ingestion during 100 km of cycling enhance
      performance in well-trained cyclists.

PMID- 9018518
TI  - Arousal pattern following central and obstructive breathing abnormalities in
      infants and children.
AB  - We analyzed the polysomnographic records of 15 children and 20 infants with
      obstructive sleep apnea (OSA) to examine the interaction between central and
      obstructive breathing abnormalities and arousal from sleep. Each patient was
      matched for age with an infant or child who had no OSA. We found that the
      majority of respiratory events in infants and children was not terminated with
      arousal. In children, arousals terminated 39.3 +/- 7.2% of respiratory events
      during quiet sleep and 37.8 +/- 7.2% of events during active (rapid-eye-movement)
      sleep. In infants, arousals terminated 7.9 +/- 1.0% of events during quiet sleep
      and 7.9 +/- 1.2% of events during active sleep. In both infants and children,
      however, respiratory-related arousals occurred more frequently after obstructive
      apneas and hypopneas than after central events. Spontaneous arousals occurred in
      all patients with OSA during quiet and active sleep. The frequency of spontaneous
      arousals was not different between children with OSA and their matched controls.
      During active sleep, however, infants with OSA had significantly fewer
      spontaneous arousals than did control infants. We conclude that arousals is not
      an important mechanism in the termination of respiratory events in infants and
      children and that electroencephalographic criteria are not essential to determine
      the clinical severity of OSA in the pediatric population.

PMID- 9018519
TI  - Endurance training affects myosin heavy chain phenotype in regenerating fast
      twitch muscle.
AB  - The aim of this study was to analyze the effects of treadmill training (2 h/day,
      5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosin heavy chain
      (MHC) isoforms during and after regeneration of a fast-twitch white muscle
      [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a
      sedentary (n = 10) or an endurance-trained (ET; n = 10) group. EDL muscle
      degeneration and regeneration were induced by two subcutaneous injections of a
      snake toxin. Five days after induction of muscle injury, animals were trained
      over a 5-wk period. It was verified that approximately 40 days after venom
      treatment, central nuclei were present in the treated EDL muscles from sedentary
      and ET rats. The changes in the expression of MHCs in EDL muscles were detected
      by using a combination of biochemical and immunocytochemical approaches. Compared
      with contralateral nondegenerated muscles, relative concentrations of types I,
      IIa, and IIx MHC isoforms in ET rats were greater in regenerated EDL muscles
      (146%, P < 0.05; 76%, P < 0.01; 87%, P < 0.01, respectively). Their elevation
      corresponded to a decrease in the relative concentration of type IIb MHC (-36%, P
      < 0.01). Although type I accounted for only 3.2% of total myosin in regenerated
      muscles from the ET group, the cytochemical analysis showed that the proportion
      of positive staining with the slow MHC antibody was markedly greater in
      regenerated muscles than in contralateral ones. Collectively, these results
      demonstrate that the regenerated EDL muscle is sensitive to endurance training
      and suggest that the training-induced shift in MHC isoforms observed in these
      muscles resulted from an additive effect of regeneration and repeated exercise.

PMID- 9018520
TI  - Windchill and the risk of tissue freezing.
AB  - Low air temperatures and high wind speeds are associated with an increased risk
      of freezing of the exposed skin. P. A. Siple and C. F. Passel (Proc. Am. Phil.
      Soc. 89: 177-199, 1945) derived their windchill index from cooling experiments on
      a water-filled cylinder to quantify the risk of frostbite. Their results are
      reexamined here. It is found that their windchill index does not correctly
      describe the convective heat transfer coefficient (hc) for such a cylinder, the
      effect of the airspeed (v) is underestimated. New risk curves have been
      developed, based on the convection equations valid for cylinders in a cross flow,
      hc infinity v0.62, and tissue freezing data from the literature. An analysis of
      the data reveals a linear relationship between the frequency of finger frostbite
      and the surface temperature. This relation closely follows a normal distribution
      of finger-freezing temperatures, with an SD of 1 degree C. As the skin surface
      temperature falls from -4.8 to -7.8 degrees C, the risk of frostbite increases
      from 5 to 95%. These data indicate that the risk of finger frostbite is minor
      above an air temperature of -10 degrees C, irrespective of v, but below -25
      degrees C there is a pronounced risk, even at low v.

PMID- 9018521
TI  - Estimating exercise stroke volume from asymptotic oxygen pulse in humans.
AB  - Noninvasive techniques have been devised to estimate cardiac output (Q) during
      exercise to obviate vascular cannulation. However, although these techniques are
      noninvasive, they are commonly not nonintrusive to subjects' spontaneous
      ventilation and gas-exchange responses. We hypothesized that the exercise stroke
      volume (SV) and, hence, Q might be accurately estimated simply from the response
      pattern of two standardly determined variables: O2 uptake (VO2) and heart rate
      (HR). Central to the theory is the demonstration that the product of Q and mixed
      venous O2 content is virtually constant (k) during steady-state exercise. Thus
      from the Fick equation, VO2 = Q.CaCO2-k, where CaCO2 is the arterial CO2 content,
      the O2 pulse (O2-P) equals SV.CaCO2-(k/HR). Because the arterial O2 content
      (CaO2) is usually relatively constant in normal subjects during exercise, O2-P
      should change hyperbolically with HR, asymptoting at SV.CaO2. In addition,
      because the asymptotic O2-P equals the slope (S) of the linear O2-HR
      relationship, exercise SV may be predicted as S/CaO2. We tested this prediction
      in 23 normal subjects who underwent a 3-min incremental cycle-ergometer test with
      direct determination of CaO2 and mixed venous O2 content from indwelling
      catheters. The predicted SV closely reflected the measured value (r = 0.80). We
      therefore conclude that, in normal subjects, exercise SV may be estimated simply
      as five times S of the linear VO2-HR relationship (where 5 is approximately
      1/CaO2).

PMID- 9018523
TI  - Ring distraction technique for measuring surface tension of sputum: relationship
      to sputum clearability.
AB  - Poor sputum clearance has been related to sputum adhesion tension. In this study,
      we describe a modified du Nouy ring method for measuring the surface tension
      (gamma) of small samples of sputum and for comparinge the calculated work of
      adhesion (Wad) for sputum specimens with the measured mucociliary
      transportability (MCTR) and cough transportability (CTR). The gamma, as measured
      by this method, correlates with gamma measured by sputum contact angle on a low
      surface-energy solid (R2 = 0.368, P = 0.03). There is a small but significant
      difference in measurements made by these two methods (P = 0.03). Wad calculated
      from the surface tension ring method is inversely correlated with CTR (R2 =
      0.181, P = 0.004) but has no correlation with MCTR in this study. The
      miniaturized ring method gives accurate and reproducible measurements of the
      surface tension of small amounts of respiratory secretions. Because sputum
      behaves enough like a liquid that the assumptions made in using the Young
      equation to calculate Wad appear valid, we also showed that the Neumann equation
      can be used to determine the surface tension of sputum by its contact angle on
      tetrafluoroethylene (Teflon).

PMID- 9018522
TI  - Chest wall and lung volume estimation by optical reflectance motion analysis.
AB  - Estimation of chest wall motion by surface measurements only allows one
      dimensional measurements of the chest wall. We have assessed on optical
      reflectance system (OR), which tracks reflective markers in three dimensions (3
      D) for respiratory use. We used 86 (6-mm-diameter) hemispherical reflective
      markers arranged circumferentially on the chest wall in seven rows between the
      sternal notch and the anterior superior iliac crest in two normal standing
      subjects. We calculated the volume of the entire chest wall and compared inspired
      and expired volumes with volumes obtained by spirometry. Marker positions were
      recorded by four TV cameras; two were 4 m in front of and two were 4 m behind the
      subject. The TV signals were sampled at 100 Hz and combined with grid calibration
      parameters on a personal computer to obtain the 3-D coordinates of the markers.
      Chest wall surfaces were reconstructed by triangulation through the point data,
      and chest wall volume was calculated. During tidal breathing and vital capacity
      maneuvers and during CO2-stimulated hyperpnea, there was a very close correlation
      of the lung volumes (VL) estimated by spirometry [VL(SP)] and OR [VL(OR)].
      Regression equations of VL(OR) (y) vs. VL(SP) (x, BTPS in liters) for the two
      subjects were given by y = 1.01x-0.01 (r = 0.996) and y = 0.96x + 0.03 (r =
      0.997), and by y = 1.04x + 0.25 (r = 0.97) and y = 0.98x + 0.14 (r = 0.95) for
      the two maneuvers, respectively. We conclude spirometric volumes can be estimated
      very accurately and directly from chest wall surface markers, and we speculate
      that OR may be usefully applied to calculations of chest wall shape, regional
      volumes, and motion analysis.

PMID- 9018524
TI  - Sodium alterations in isolated rat heart during cardioplegic arrest.
AB  - Triple-quantum-filtered (TQF) Na nuclear magnetic resonance (NMR) without
      chemical shift reagent is used to investigate Na derangement in isolated
      crystalloid perfused rat hearts during St. Thomas cardioplegic (CP) arrest. The
      extracellular Na contribution to the NMR TQF signal of a rat heart is found to be
      73 +/- 5%, as determined by wash-out experiments at different moments of ischemia
      and reperfusion. With the use of this contribution factor, the estimated
      intracellular Na ([Na+]i) TQF signal is 222 +/- 13% of preischemic level after 40
      min of CP arrest and 30 min of reperfusion, and the heart rate pressure product
      recovery is 71 +/- 8%. These parameters are significantly better than for stop
      flow ischemia: 340 +/- 20% and 6 +/- 3%, respectively. At 37 degrees C, the
      initial delay of 15 min in [Na+]i growth occurs during CP arrest along with
      reduced growth later (approximately 4.0%/min) in comparison with stop-flow
      ischemia (approximately 6.7%/min). The hypothermia (21 degrees C, 40 min) for the
      stop-flow ischemia and CP dramatically decreases the [Na+]i gain with the highest
      heart recovery for CP (approximately 100%). These studies confirm the enhanced
      sensitivity of TQF NMR to [Na+]i and demonstrate the potential of NMR without
      chemical shift reagent to monitor [Na+]i derangements.

PMID- 9018525
TI  - Friction in airway smooth muscle: mechanism, latch, and implications in asthma.
AB  - In muscle, active force and stiffness reflect numbers of actin-myosin
      interactions and shortening velocity reflects their turnover rates, but the
      molecular basis of mechanical friction is somewhat less clear. To better
      characterize molecular mechanisms that govern mechanical friction, we measured
      the rate of mechanical energy dissipation and the rate of actomyosin ATP
      utilization simultaneously in activated canine airway smooth muscle subjected to
      small periodic stretches as occur in breathing. The amplitude of the frictional
      stress is proportional to eta E, where E is the tissue stiffness defined by the
      slope of the resulting force vs. displacement loop and eta is the hysteresivity
      defined by the fatness of that loop. From contractile stimulus onset, the time
      course of frictional stress amplitude followed a biphasic pattern that tracked
      that of the rate of actomyosin ATP consumption. The time course of hysteresivity,
      however, followed a different biphasic pattern that tracked that of shortening
      velocity. Taken together with an analysis of mechanical energy storage and
      dissipation in the cross-bridge cycle, these results indicate, first, that like
      shortening velocity and the rate of actomyosin ATP utilization, mechanical
      friction in airway smooth muscle is also governed by the rate of cross-bridge
      cycling; second, that changes in cycling rate associated with conversion of
      rapidly cycling cross bridges to slowly cycling latch bridges can be assessed
      from changes of hysteresivity of the force vs. displacement loop; and third, that
      steady-state force maintenance (latch) is a low-friction contractile state. This
      last finding may account for the unique inability of asthmatic patients to
      reverse spontaneous airways obstruction with a deep inspiration.

PMID- 9018578
TI  - TEACCH-supported employment program.
AB  - Division TEACCH has served over 100 persons with autism through its supported
      employment program. Three models of supported employment are utilized: individual
      placement model, dispersed enclave model, and mobile crew model. Within each of
      these models there is an emphasis on utilizing individual strengths and
      interests, identifying appropriate jobs, and providing extensive long-term
      support. A retention rate of 89% demonstrates the success of the program which is
      due in large part to the broad array of long-term support services that are
      provided.

PMID- 9018579
TI  - Families of children with Prader-Willi syndrome: stress-support and relations to
      child characteristics.
AB  - This study examined stress-support in 42 families of 3 to 18-year-old children
      with Prader-Willi syndrome. Parents were asked about themselves and their
      families, their child with Prader-Willi syndrome, family supports, and family
      stress. Compared to reported stress levels in families of children with mixed
      etiologies of retardation, parents of children with Prader-Willi syndrome showed
      higher levels of parent and family problems, and comparable levels of pessimism.
      Parents of children with Prader-Willi syndrome listed other family members and
      friends as their main supporters; often such supporters lived outside of the
      respondent's town or city. Although the child's age, IQ, and degree of obesity
      were not related to familial stress, families experienced greater stress when the
      child showed more behavior problems overall, more externalizing and internalizing
      problems, and more problems on five of the nine narrow-band domains of
      Achenbach's Child Behavior Checklist.

PMID- 9018580
TI  - Counting abilities in autism: possible implications for central coherence theory.
AB  - We examined the claim that children with autism have a "weak drive for central
      coherence" which biases them towards processing information at an analytic rather
      than global level. This was done by investigating whether children with autism
      would rapidly and automatically enumerate a number of dots presented in a
      canonical form, or count each dot individually to obtain the total. The time
      taken to count stimuli was compared across three participant groups: children
      with autism, children with moderate learning difficulties, and normally
      developing children. There were 22 children in each group, and individuals were
      matched across groups on the basis of verbal mental age. Results implied that
      children with autism did show a tendency towards an analytic level of processing.
      However, though the groups differed on measures of counting speeds, the number or
      children showing patterns of global or analytic processing did not differ
      significantly across the groups. Whether these results implicate a weak drive for
      central coherence in autism, which is both specific to, and pervasive in the
      disorder, is discussed.

PMID- 9018581
TI  - Linking parental perceptions to interactions in young children with autism.
AB  - This study examines the relation of parental perceptions and observed parent
      child interactive behaviors. Samples observed included normally developing
      children, children with autism, and children with mental retardation who were
      equivalent on mental age. Parental perceptions of children's temperament and
      parental feelings of parenting stress were examined. Results indicated that
      parental perceptions of autistic children's behavior were more often linked to
      actual child and parental behaviors than in the comparison samples. Parents who
      reported their autistic children as more difficult in temperamental style had
      children who were less engaged during a social game with the parent and less
      responsive in interaction with an experimenter. Parents who reported greater
      stress had autistic children who were less responsive in social interactions with
      others.

PMID- 9018582
TI  - Inhibitory function in nonretarded children with autism.
AB  - This study examined inhibitory function in nonretarded children with autism (n =
      13) and normally developing controls (n = 13) matched on age and IQ. Tasks
      measuring motor and cognitive components of inhibition were administered to both
      groups. On the Stop-Signal paradigm, children with autism were able to inhibit
      motor responses to neutral and prepotent stimuli as well as control subjects. On
      the Negative Priming task, the groups were equally capable of inhibiting
      processing of irrelevant distractor stimuli in a visual display. Results suggest
      that at least two components of inhibition are spared in individuals with autism,
      standing in contrast to flexibility and other executive deficits that have been
      found in previous studies. These findings may help distinguish children with
      autism from those with other neurodevelopmental conditions that involve executive
      dysfunction.

PMID- 9018583
TI  - Brief report: response to methylphenidate in two children with Williams syndrome.

PMID- 9018584
TI  - Brief report: reliability and validity of instruments for assessing psychotropic
      medication effects on self-injurious behavior in mental retardation.

PMID- 9018585
TI  - Pervasive developmental disorder, commonly abbreviated as PDD.

PMID- 9018600
TI  - Ancestral inference from samples of DNA sequences with recombination.
AB  - The sampling distribution of a collection of DNA sequences is studied under a
      model where recombination can occur in the ancestry of the sequences. The
      infinitely-many-sites model of mutation is assumed where there may only be one
      mutation at a given site. Ancestral inference procedures are discussed for:
      estimating recombination and mutation rates; estimating the times to the most
      recent common ancestors along the sequences; estimating ages of mutations; and
      estimating the number of recombination events in the ancestry of the sample.
      Inferences are made conditional on the configuration of the pattern of mutations
      at sites in observed sample sequences. A computational algorithm based on a
      Markov chain simulation is developed, implemented, and illustrated with examples
      for these inference procedures. This algorithm is very computationally intensive.

PMID- 9018601
TI  - Parallel computing of physical maps--a comparative study in SIMD and MIMD
      parallelism.
AB  - Ordering clones from a genomic library into physical maps of whole chromosomes
      presents a central computational problem in genetics. Chromosome reconstruction
      via clone ordering is usually isomorphic to the NP-complete Optimal Linear
      Arrangement problem. Parallel SIMD and MIMD algorithms for simulated annealing
      based on Markov chain distribution are proposed and applied to the problem of
      chromosome reconstruction via clone ordering. Perturbation methods and problem
      specific annealing heuristics are proposed and described. The SIMD algorithms are
      implemented on a 2048 processor MasPar MP-2 system which is an SIMD 2-D toroidal
      mesh architecture whereas the MIMD algorithms are implemented on an 8 processor
      Intel iPSC/860 which is an MIMD hypercube architecture. A comparative analysis of
      the various SIMD and MIMD algorithms is presented in which the convergence,
      speedup, and scalability characteristics of the various algorithms are analyzed
      and discussed. On a fine-grained, massively parallel SIMD architecture with a low
      synchronization overhead such as the MasPar MP-2, a parallel simulated annealing
      algorithm based on multiple periodically interacting searches performs the best.
      For a coarse-grained MIMD architecture with high synchronization overhead such as
      the Intel iPSC/860, a parallel simulated annealing algorithm based on multiple
      independent searches yields the best results. In either case, distribution of
      clonal data across multiple processors is shown to exacerbate the tendency of the
      parallel simulated annealing algorithm to get trapped in a local optimum.

PMID- 9018602
TI  - A self-organizing cognitive network of antibody repertoire development.
AB  - A self-organizing cognitive network is mapped here onto the Id network model. The
      weight-vectors in this network represent some important topographical and
      biophysical parameters in the antibody-antigen affinity landscape. The Kohonen
      layers in the network correspond to affinity clones and the involved algorithm
      simulates the operations of clonal selection, hypermutation, differentiation,
      diversity, and affinity maturation. Two significant features of this model are:
      (i) a computationally feasible and biophysically informative representation of
      the para/epitopes, and (ii) the ability to perform simultaneous (parallel) and
      associative computations in a multidimensional shape-space. Computational
      experiments with real data have shown cognitive properties of this network. The
      results also indicate scope in quantitative characterization of the metadynamics
      of the above operations/weights in the adaptive development of the antibody
      repertoire.

PMID- 9018603
TI  - A protein class database organized with ProSite protein groups and PIR
      superfamilies.
AB  - A protein class (ProClass) database is developed as a "value-added" "second
      generation" database organized according to family relationships. The database
      collects non-redundant protein sequence entries from SwissProt and PIR databases,
      and classifies them in families defined collectively by the ProSite protein
      groups and PIR superfamilies. The major objectives of the database are to
      maximize family information retrieval, to provide speedy family identification,
      and to help organizing existing protein sequence databases. The database has two
      sub-databases: PCFam (ProClass Family) to define protein families and provide
      links to ProSite patterns and PIR superfamilies, and PCSeq (ProClass Sequence) to
      describe sequence entries and provide links to PCFam, SwissProt, PIR, and ProSite
      databases. The current ProClass release has a total of 85,165 sequence entries,
      about half of which are classified in 3072 ProClass families; it also contains
      10,431 newly established SwissProt-PIR links. The database can help reveal domain
      structures of related families, define new ProSite and PIR families, and provide
      family assignments for unclassified sequence entries. New ProSite and PIR family
      members are readily identified via database cross-reference, including 9437
      SwissProt entries and 8522 PIR entries. False negative family members missed by
      both ProSite and PIR are detected using a neural network family identification
      system. The newly identified superfamily memberships are being incorporated into
      the current PIR database releases in a collaborative effort with the PIR. The
      ProClass database is accessible through anonymous FTP and on-line search on the
      World Wide Web.

PMID- 9018604
TI  - Progressive multiple alignment with constraints.
AB  - A progressive alignment algorithm produces a multialignment of a set of sequences
      by repeatedly aligning pairs of sequences and/or previously generated alignments.
      We describe a method for guaranteeing that the alignment generated by a
      progressive alignment strategy satisfies a user-specified collection of
      constraints about where certain sequence positions should appear relative to
      others. Our main result is an algorithm to compute just the "prime" constraints
      that are implied by the user-given constraints; these are shown to be precisely
      the constraints that the alignment algorithm must obey. In practice, the time
      required to handle constraints is negligible and frequently much less than the
      time saved because the constraints permit searching a restricted region of the
      dynamic-programming grid. An alignment of the beta-like globin gene cluster of
      several mammals illustrates the practicality of the method.

PMID- 9018605
TI  - Principal component analysis and large-scale correlations in non-coding sequences
      of human DNA.
AB  - We have calculated a full set of second-order correlation functions of
      nucleotides in noncoding DNA. They are found to be independently invariant in
      regard to permutations of A and T, and also C and G. Considering correlation
      functions as a 4 x 4 matrix with a symmetrical basis, we have found the principal
      components-objects with zero cross-correlations. These three principal components
      are present the base compositions: (A + T - C - G), (A - T), (C - G). The long
      range behavior of these principal components yields power-law dependencies with
      different critical exponents.

PMID- 9018606
TI  - Repetitive strain: putting it in perspective.

PMID- 9018607
TI  - Repetitive strain in the workplace.

PMID- 9018608
TI  - Repetitive upper-extremity motions in the workplace are not hazardous.

PMID- 9018609
TI  - Factors prolonging disability in work-related cumulative trauma disorders.
AB  - Workers' compensation costs for management of soft tissue disorders continue to
      increase. The complexity of medical management of these cases has increased due
      to social factors. The purpose of this study is to improve the physician's
      ability to recognize nonmedical issues that prevent a rapid return to employment.
      A classification system is presented that will allow the clinician to identify
      administrative and pyschosocial issues that prolong disability. Additionally, the
      patients' job demands were classified by known ergonomic risk factors. The system
      was applied retrospectively to 50 random cases referred to two occupational hand
      clinics over a 1-year period. The results indicated that the psychosocial
      classification of the patient and the current employment status are the most
      important factors in prolonging disability workers.

PMID- 9018610
TI  - Corrective osteotomy for scaphoid malunion: technique and long-term follow-up
      evaluation.
AB  - Five patients with dorsal intercalated segment instability underwent corrective
      osteotomy for symptomatic scaphoid malunion. Follow-up examination at an average
      of nearly 9 years after the procedure (range, 1.5-19 years) revealed that all had
      improvement in range of motion (ROM). Total active ROM improved from a mean of
      127 degrees (range, 95 degrees-165 degrees) to a mean of 156 degrees (range, 95
      degrees-214 degrees). Grip strength increased from a mean of 16 kg (range, 14-35
      kg) to a mean of 32 kg (range, 24-48 kg). The wrist score improved from an
      average of 19 to 75. The preoperative intrascaphoid and carpal malalignments were
      reduced, as demonstrated by trispiral tomography. Symptomatically, all patients
      reported improvement. All osteotomies healed within 5.5 months of the procedure.
      No case of avascular necrosis was noted. Mild radioscaphoid arthrosis is apparent
      in four patients and a preexisting midcarpal arthrosis persists in one patient.
      Corrective osteotomy for scaphoid malunion may have a role in the prevention or
      slowing of the onset of premature arthritis in young patients with high
      functional demands. A technique is described.

PMID- 9018611
TI  - The effects of exercise on ligamentous stiffness in the wrist.
AB  - The purpose of this study was to determine if exercise alters wrist joint laxity,
      as measured by the mechanical behavior of the scaphoid bone. The load
      displacement behavior of the scaphoid was studied in the palmar-dorsal direction
      in both wrists of 7 healthy volunteers (n = 14) before and after 2 exercise
      protocols (grip and push-up). When compared to the rested values, both exercise
      protocols significantly increased the displacement at 40 N by 47% (grip) and by
      34% (push-up). Accordingly, the stiffness decreased significantly by 36% (grip)
      and by 32% (push-up). Partial recovery was documented after 1 hour of rest and
      there were no differences between any of the groups after 24 hours of rest. The
      increase in laxity documented during these exercise protocols reduces the
      ligament loads at comparable wrist positions and may thereby reduce the
      likelihood of traumatic ligamentous injury during participation in strenuous
      activity or sports.

PMID- 9018612
TI  - Perilunate dislocation and fracture dislocation: a critical analysis of the volar
      dorsal approach.
AB  - A combined volar-dorsal approach was used to treat 11 perilunate dislocations and
      fracture dislocations between 1989 and 1994. The mean average age of the patients
      was 38 years, and the mean average time between injury and surgery was 13 hours.
      Outcome was assessed after an average of 30 months. Results were based on
      measurements of grip strength, range of motion, radiographs, and patient
      satisfaction. Patient satisfaction was high in 9 of 11 patients. Seven had
      satisfactory pain relief, and 5 had returned to their previous occupation without
      limitation. The wrist flexion-extension arc and grip strength averaged 71% and
      77%, respectively, compared to the opposite side. Follow-up radiographs
      demonstrated complete union of all 8 wrist fractures. For all 11 patients, the
      carpal height ratio averaged 0.50. Neither scapholunate dissociation nor
      significant dorsal intercalated segmental instability existed, but 1 wrist
      developed scapholunate advanced collapse arthritis. Although perilunate
      instability patterns of injury create significant derangement in carpal anatomy
      and are among the most challenging of traumatic wrist injuries to correct, our
      results show that a combined volar-dorsal approach can be used safely and
      effectively to restore normal intercarpal relationships and provide fixation for
      accompanying fractures. For the majority of patients, the outcome after this
      procedure is characterized by acceptable pain relief as well as functional motion
      and grip strength.

PMID- 9018613
TI  - Isolated tears of the triangular fibrocartilage: management by early arthroscopic
      repair.
AB  - To evaluate the efficacy of arthroscopic repair of the triangular fibrocartilage
      complex (TFCC) tears treated within 4 months after injury, functional outcome
      after repair was determined following arthroscopic repair in 24 patients. The
      patients' average age was 31 years (range, 22-38 years); the average follow-up
      period was 34 months (range, 26-48 months). All patients had wrist pain limiting
      their participation in work prior to surgery. Patients with central attrition
      tears identified by arthroscopy were excluded from the study. Twenty-three
      patients had a preoperative arthrogram. Twelve of the patients with positive
      arthrogram findings had an avulsion of the TFCC from the sigmoid notch (Palmer
      type 1D tears). Of the eleven patients with negative arthrograms, 10 had ulnar
      tears in capsular attachments of the TFCC. The ulna variance averaged 0.2 mm +/-
      0.6 mm. Separate arthroscopic techniques were developed for reattaching the TFCC
      to the radius (nine patients) versus to the peripheral capsule on the volar or
      ulnar side of the wrist (eight patients). Postoperatively, there was a
      significant relief of pain (p < .01). Postoperative range of motion averaged 89%
      +/- 9% SD of the contralateral side, and grip strength averaged 85% +/- 20% SD of
      the contralateral side. Thirteen of the 19 patients returning to work did so in
      their original jobs.

PMID- 9018614
TI  - Nonunion rates of limited carpal arthrodesis: a meta-analysis of the literature.
AB  - Numerous types of limited intercarpal arthrodeses have been reported in dozens of
      articles in the English-language medical literature. The nonunion rate varies
      considerably within and between the different types of arthrodeses. This may be
      due in part to the small number of cases in most studies. The data on the number
      of good results and nonunion rates for 27 different types of limited carpal
      arthrodeses reported in the English-language medical literature from 1946 to 1993
      were collected, and for each study, the 95% confidence intervals (95% CI) were
      calculated. The studies were then combined for specific types of arthrodeses and
      the overall nonunion rates and confidence intervals were calculated to more
      accurately determine the actual nonunion rate expected for limited intercarpal
      arthrodeses. Nonunion rates (95% CI) for the most popular types of limited
      arthrodeses were as follows: of 385 scaphotrapezium-trapezoid arthrodeses
      reported, there was a 14% nonunion rate (95% CI, 11%-18%); of 104 lunotriquetral
      arthrodeses, the nonunion rate was 27% (95% CI, 19%-36%); and of 17 scapholunate
      arthrodeses, the nonunion rate was 47% (95% CI, 26%-69%).

PMID- 9018615
TI  - Congenital synchondrosis of the scaphotrapezio-trapezoidal joint.
AB  - Incomplete cavitation of the cartilaginous precursor of the carpus during the
      fourth to eighth weeks of intrauterine life results in carpal synostosis or
      synchondrosis, which becomes radiographically apparent as the carpus ossifies.
      Such anomalies occur rarely, are generally believed to be asymptomatic, and are
      usually discovered as incidental radiographic findings. We present two cases of
      symptomatic, nonsyndromic congenital synchondrosis of the scaphotrapezio
      trapezoidal joint, a type of carpal coalition not previously reported.

PMID- 9018616
TI  - Isolated palmar radiocarpal dislocation and ulnar translocation: a case report
      and review of the literature.

PMID- 9018617
TI  - Scapholunate ligament disruption in a skeletally immature patient: a case report.
AB  - Scapholunate ligament tears are rare in skeletally immature people because the
      force of impact is absorbed by the cartilaginous carpus. We present a case of a
      boy who ruptured this ligament after a fall.

PMID- 9018618
TI  - Open dislocation of the carpal scaphoid: a case report.
AB  - A case of an open volar scaphoid dislocation is presented. The patient was
      treated surgically, with open reduction of the scaphoid and pinning to the
      lunate. After 9 years, good clinical and radiographic results were obtained.

PMID- 9018619
TI  - Rotary dislocation of the capitate: a case report.

PMID- 9018620
TI  - Giant cell tumors of the bones of the hand.
AB  - The cases of all patients with a diagnosis of giant cell tumor of bone occurring
      in the hand and seen at the Mayo Clinic during a 50-year period were reviewed to
      assess the results of treatment. There were 5 lesions in the phalanges, 7 in the
      metacarpals, and 1 in the scaphoid. The mean duration of symptoms and interval to
      recurrence were shorter than those seen in giant cell tumor of bone occurring in
      sites other than the hand. Radiographically advanced disease was common at
      presentation. Local recurrence was seen after 11 of 14 intralesional procedures
      (79%) involving curettage or curettage and bone grafting. Local recurrence was
      seen after 5 of 14 procedures (36%) involving local excision, wide excision,
      amputation, or ray resection. Lung metastases developed in 2 patients after or
      concurrent with local recurrence. Local control was most effectively achieved
      with wide excision or ray resection.

PMID- 9018621
TI  - Tubular versus conventional repair of median and ulnar nerves in the human
      forearm: early results from a prospective, randomized, clinical study.
AB  - Injury to a peripheral nerve is followed by local synthesis and release of
      neurotrophic factors of importance for the regeneration process. This concept was
      adopted for repair of transected human median and ulnar nerves in the forearm. As
      an alternative to conventional microsurgical repair of the nerve trunk, silicone
      tubes of appropriate size were used to enclose the injury zone, intentionally
      leaving a gap measuring 3-4 mm between the nerve ends inside the tube. The early
      results from a prospective, randomized, clinical study comparing this principle
      with conventional microsurgical technique for repair of human median and ulnar
      nerves, is presented. Eighteen patients (14 men and 4 women), aged 12-72 (mean,
      29.5) years, were randomized to either tubulization (11 cases) or conventional
      microsurgical repair (7 cases). A battery of tests for sensory and motor
      functions of the hand were carried out at regular intervals for up to 1 year
      after surgery. The results show no difference between the both techniques, with
      the exception of perception of touch, which showed a significant difference (p <
      .05) at the 3-month checkup in favor of the tubulization technique. At re
      exploration 11 months after the initial procedure (1 case), the former gap was
      replaced by regenerated nerve tissue in direct continuity with the proximal and
      distal parts of the nerve trunk, the exact level of the former injury being
      impossible to identify. Study data demonstrate an intrinsic capacity of human
      major nerve trunks to reconstruct themselves in a preformed space when an optimal
      environment is offered and the surgical trauma is minimized.

PMID- 9018622
TI  - Biomechanical and histologic characteristics of canine flexor tendon repair using
      early postoperative mobilization.
AB  - The purpose of this experimental study was to evaluate the mechanical and
      histologic healing of flexor tendon repairs using an early active motion
      protocol. Three different flexor tendon repair techniques in zone II were used.
      Forty-seven lacerated canine flexor profundus tendons from 25 dogs were repaired
      and evaluated at 5, 10, and 21 days after surgery. Eight of 9 Kessler repairs
      ruptured at days 5 and 10. None of the 19 Savage repairs or the 19 dorsal tendon
      splint repairs ruptured; 3 of 19 dorsal tendon splint repairs failed owing to
      adhesions. Smooth tendon gliding was obtained in all specimens in which repair
      was successful. The gap strength values for both the Savage and dorsal tendon
      splint repairs improved significantly for day-21 specimens compared to day-5 or
      day-10 specimens. The ultimate tensile strength showed no reduction during the 3
      week period of tendon healing for both repairs. Histologically, there was
      evidence of progressive healing without surrounding adhesions. The improved
      suture techniques have the potential to withstand the stress produced by active
      digital motion protocols.

PMID- 9018623
TI  - The use of routine wrist radiography in the evaluation of patients with carpal
      tunnel syndrome.
AB  - The objective of this study was to evaluate the use of routine wrist radiography
      in the evaluation of patients with carpal tunnel syndrome (CTS). In the setting
      of a community-based hand surgery practice, we performed a retrospective review
      of charts and radiographs for 300 consecutive patients (447 wrists) meeting
      clinical and electrophysiologic criteria for CTS. Data on all patients included
      information obtained by the use of medical history questionnaires, physical
      examinations, nerve conduction studies, and radiographs of the wrist.
      Abnormalities were noted in 146 of 447 wrist radiographs (33%). Eighty-three
      (18.6%) had abnormalities that might have been implicated in the development of
      CTS, although these findings would not alter management. For only 2 of 447 wrists
      (0.4% of wrists; 0.6% of patients) were there radiographic findings of
      therapeutic significance. Radiographic charges were calculated to be $5,869 to
      $20,115 for each finding of therapeutic significance. We conclude that wrist
      radiographs should not be performed routinely in patients with CTS, owing to the
      low yield of useful information.

PMID- 9018625
TI  - Ulnar nerve decompression by transposing the nerve and Z-lengthening the flexor
      pronator mass: clinical outcome.
AB  - Controversy surrounds the reliability of methods of treating ulnar nerve
      compression at the elbow. The effectiveness of submuscular anterior nerve
      transposition was evaluated in 33 limbs of 31 patients. The flexor-pronator Z
      lengthening technique, without internal neurolysis, was used. Results were
      determined by patient chart reviews. Severity of preoperative nerve compression
      was measured using Dellon's classification. Of the 33 limbs, 6 had mild
      preoperative nerve compression; 7, moderate; and 20, severe. Overall outcome was
      evaluated using a modification of the Bishop rating system. At a mean follow-up
      period of 49 months, 12 limbs (36%) had excellent results, 20 limbs (61%) had
      good results, and 1 limb (3%) had a poor result. These findings indicate that
      submuscular ulnar nerve transposition using the flexor-pronator Z-lengthening
      technique without internal neurolysis is a reliable method of treating ulnar
      nerve compression at the elbow.

PMID- 9018624
TI  - Flexor carpi radialis approach for carpal tunnel release.
AB  - A technique for dividing the transverse carpal ligament has been developed in
      order to decrease the incidence of pillar pain. The carpal ligament splits around
      the flexor carpi radialis (FCR) tendon into two leaves as it approaches its
      radial attachments. The new approach uses the FCR as a guide to divide these
      attachments under direct visualization, thereby releasing the carpal tunnel. This
      technique has been used on 87 hands, with 79 (91%) obtaining complete or partial
      relief of preoperative symptoms. Pillar tenderness resolved quickly and there
      were few complications. The FCR approach to carpal tunnel release couples the
      advantages of direct visualization of the carpal canal contents with the
      decreased disruption of palmar skin and soft tissues, thereby reducing pillar
      pain without increasing the risk of surgical complications.

PMID- 9018626
TI  - Dislocating medial triceps and ulnar neuropathy in three generations of one
      family.
AB  - Variations in the medial triceps in conjunction with bilateral ulnar neuropathy
      have been identified in three generations of one family also possessing the
      phenotype of Waardenburg syndrome (a rare autosomal-dominant disorder with
      clinical features including cochlear deafness, dystopia canthorum, and
      pigmentation problems). To our knowledge, no other inherited condition with
      triceps anomalies has been reported. Study of this family provided insight into
      the relationship between dislocating medial triceps and ulnar neuropathy and
      demonstrated that a broad spectrum of clinical presentations exists-from being
      completely asymptomatic to producing symptomatic snapping and ulnar neuropathy.

PMID- 9018627
TI  - Injection versus surgery in the treatment of trigger finger.
AB  - One hundred nine trigger fingers in 102 patients were reviewed with respect to
      management plan and response to treatment. Thirty-four digits eventually
      underwent surgical release of the A1 pulley, while the other 75 digits were
      treated with local steroid injection only. All patients were evaluated with
      respect to clinical resolution of symptoms, dollar cost of treatment, and general
      satisfaction as measured with a post-treatment questionnaire. These data suggest
      that surgical management may be the next best option in patients with trigger
      finger who continue to be symptomatic after a single injection. Although surgical
      release of the A1 pulley cost our Medicare patients $250.00 more than a second
      injection, this additional cost may be offset by the benefit conferred through
      permanency of relief. Subjective data from the patient questionnaire responses
      also support surgery as a reasonable choice after one injection failure. The
      information from this study better delineates differences between injection and
      surgery as treatment choices and may aid the patient and physician in choosing an
      individually optimal care plan.

PMID- 9018628
TI  - The results of surgical treatment of trigger finger.
AB  - A three-part retrospective study was undertaken to review the long-term results
      of surgical treatment of trigger finger. Seventy-five patients were identified by
      chart review. Fifty-nine of these were assessed by a telephone survey, with a
      mean follow-up period of 48 months (range, 6-70 months). Forty-six patients (78%)
      underwent follow-up physical examination. Surgical treatment was successful in
      all patients. Ninety-seven percent of patients had complete resolution of
      triggering, and the rest had significant improvement of symptoms. The recurrence
      rate was 3%, with only a single patient requiring reoperation. Complications were
      infrequent and resulted in minimal morbidity. No nerve injuries, tendon
      bowstringing, or ulnar deviation of the digits were observed. There were no wound
      infections. Although steroid injections should remain the initial remedy for most
      trigger fingers, surgical intervention is highly successful for conservative
      treatment failures and should be considered for patients desiring quick and
      definitive relief from this disability.

PMID- 9018629
TI  - Percutaneous release of trigger digit with and without cortisone injection.
AB  - Percutaneous release was done using the tip of an 18-gauge, 2.5-cm-long needle,
      mounted on a 3-mL3 syringe in 225 trigger digits. It was successful in 92 (89%)
      of the digits without cortisone injection (n = 105) and in 115 (96%) of the
      digits with cortisone injection (n = 120). Negligible or intermittent pain
      persisted for 8 weeks in the noncortisone group and 6 weeks in the cortisone
      group after percutaneous release. Of the first 10 digits, 2 needed repeat
      percutaneous release. With modification of technique, the incidence of repeat
      percutaneous release was zero in both groups. Open release was needed in 8% in
      the noncortisone group and 3% in the cortisone group. The procedure was done
      under local infiltration anesthesia in the office. This reduced patient anxiety,
      inconvenience and hospital cost.

PMID- 9018630
TI  - The acute pathologic changes of paint-injection injury and correlation to
      surgical treatment: a report of two cases.
AB  - The early histologic changes of digital tissues after paint-injection injury
      support the urgent need to remove all contaminated tissue. Paint causes immediate
      tissue necrosis on contact and then incites an immediate necrotizing inflammatory
      reaction that persists if the tissues are not completely debrided. Early
      histopathologic changes include vessel thrombosis, tissue necrosis, and acute
      necrotizing inflammatory infiltrate, all occurring only hours after injection
      injury. In light of these histologic changes, if paint cannot be completely
      removed from digital arteries in an attempt to salvage the finger, then the wound
      should be left open and the finger monitored for further necrosis in response to
      the retained paint.

PMID- 9018631
TI  - Repetitive strain injuries and cumulative trauma disorders.

PMID- 9018632
TI  - Repetitive strain injuries and cumulative trauma disorders.

PMID- 9018633
TI  - Repetitive strain injuries and cumulative trauma disorders.

PMID- 9018634
TI  - Repetitive strain injuries and cumulative trauma disorders.

PMID- 9018635
TI  - Repetitive strain injuries and cumulative trauma disorders.

PMID- 9018636
TI  - Repetitive strain injuries and cumulative trauma disorders.

PMID- 9018637
TI  - Repetitive strain injuries and cumulative trauma disorders.

PMID- 9018638
TI  - Hypoplastic thumbs.

PMID- 9018639
TI  - Electrodiagnostic testing and carpal tunnel release outcome.

PMID- 9018640
TI  - Chronic medical disorders during pregnancy. Guidelines for prescribing drugs.
AB  - This report summarizes experience with representative drugs used to treat
      patients with medical disorders existing before pregnancy. Preconception
      counseling is ideal for determining whether drug therapy needs to be continued or
      altered. Focusing on the underlying disorder or morbid co-conditions, not the
      drug alone, may explain any additional hazards to the fetus. Avoiding multiple
      medications and selecting that which is presumably safest are encouraged. The
      best means of monitoring the safety and efficacy of therapy should be determined.
      Few drugs and their metabolites are linked to either specific birth defects or
      life-threatening problems, but their effects on the developing fetal circulation
      and central nervous systems are difficult to predict. Despite attempts to
      minimize fetal exposure, an increase in either the daily dose or duration of drug
      therapy may be necessary for optimal results. Although no drug is absolutely
      safe, the healthiest mother is most likely to deliver the healthiest infant.

PMID- 9018641
TI  - Managing residual trophoblastic tissue. Hysteroscopy for directing curettage.
AB  - OBJECTIVE: To describe our experience with selective removal of residual
      intrauterine trophoblastic tissue via hysteroscopy. METHODS: This is a
      descriptive report. Eighteen patients, 16 postabortion and 2 postpartum,
      underwent a hysteroscopic procedure for removal of residual trophoblastic tissue
      causing continuous bleeding. At hysteroscopy, a cutting loop was used as a
      curette for selective removal of the adherent residual tissue, while interference
      with the rest of the endometrial surface was avoided. RESULTS: Complete removal
      of the suspected residual tissue was achieved in all patients. Histology
      confirmed the curettings as trophoblastic remnants. No complications were
      reported during or immediately after the procedure. The median operative time was
      10 minutes (range, 8-20). In all cases the bleeding stopped shortly after the
      procedure. In each patient, postoperative ultrasonography revealed a uterine
      cavity free of residual tissue. Five of the patients underwent second-look
      hysteroscopy several weeks later, and no signs of further residual tissue were
      observed. CONCLUSION: Selective curettage of residual trophoblastic tissue
      directed by hysteroscopy is an easy and short procedure and might be preferable
      to conventional, nonselective, blind curettage.

PMID- 9018642
TI  - Neutrophil activation in preeclampsia. Are defensins and lactoferrin elevated in
      preeclamptic patients?
AB  - OBJECTIVE: To determine if human defensins and lactoferrin, both markers of
      neutrophil activation, are elevated in preeclamptic plasma. STUDY DESIGN: Blood
      samples were obtained from 18 preeclamptic and 29 normal pregnant women in the
      third trimester. Demographic and clinical data were obtained from the medical
      record. No patient had evidence of labor and/or infection when blood was drawn.
      Preeclamptic patients were defined by elevated blood pressure, 140/90 mm Hg,
      proteinuria of > 300 mg in a 24-hour collection and hyperuricemia. Human
      defensins and lactoferrin were measured by enzyme immunoassay of plasma samples
      diluted 1:100 and 1:10, respectively. Standard curve values ranged from 0.25 to
      16 ng/mL. Data for human defensins and lactoferrin are presented as median values
      +/-SE. Statistical analysis included Student's t test for comparison of clinical
      data, Mann-Whitney U test for comparison of absolute values between groups and
      Fisher's exact test, when appropriate. RESULTS: There was no difference in age or
      estimated gestational age between the two groups. There were more nulliparous
      patients in the preeclamptic group. Human defensin levels were significantly
      elevated (P = .005) in plasma of preeclamptic patients (25.1 ng/mL +/- 16.2) as
      compared to normal controls (9.0 ng/mL +/- 8.9). Nine of 18 (50%) preeclamptic
      patients and 2 of 29 (7%) normal controls had defensin levels above the low point
      on the standard curve (P = .001). There was no difference in lactoferrin levels
      between the two groups. CONCLUSION: Our results suggest that preeclampsia is
      associated with neutrophil activation. The biologic effect of elevated human
      defensins in preeclamptic plasma remains to be determined.

PMID- 9018643
TI  - Laparoscopy during pregnancy. A survey of laparoendoscopic surgeons.
AB  - OBJECTIVE: The purpose of this study was to survey the Society of
      Laparoendoscopic Surgeons (SLS) for their experience with laparoscopy during
      pregnancy and to develop a database on the safety and complications of
      laparoscopy in pregnancy. STUDY DESIGN: A survey questionnaire was mailed to
      16,329 laparoscopic surgeons from the SLS mailing database. Seven questions were
      asked: number of laparoscopic procedures in pregnancy, type of operation,
      gestational age, intraoperative and postoperative complications, insufflation
      agent and insufflation pressure. Only surgeons who had performed laparoscopic
      procedures in pregnancy were asked to return surveys. RESULTS: One hundred ninety
      two (1.2%) surveys were returned. Complete information was available on 413
      laparoscopic cases. There were five intraoperative complications, including
      inadvertent placement of a Veress needle into a pregnant uterus. There were 10
      postoperative complications. CONCLUSION: This is the first report to specifically
      address the safety and complications of laparoscopy in pregnancy. This study
      suggests that laparoscopy may be safe during pregnancy; however, it was limited
      by the biases of surveys and retrospective studies.

PMID- 9018644
TI  - AGUS in cervical endometriosis.
AB  - OBJECTIVE: To evaluate cervical endometriosis as a source of abnormal glandular
      cells in cervicovaginal smears. STUDY DESIGN: Histologically documented cases of
      cervical endometriosis with concurrent cervicovaginal smears were reviewed. The
      cytologic specimens were evaluated for the presence of glandular abnormalities.
      RESULTS: There were eight cases of superficial endometriosis (five of which had
      concurrent tuboendometrioid glandular metaplasia) and two cases of deep
      endometriosis in this series. Five of the eight cases of superficial
      endometriosis had abnormal glandular cells in the smears; neither of two cases of
      deep endometriosis had glandular abnormalities. Four of the eight cases of
      superficial endometriosis had previously undergone conization for cervical
      intraepithelial neoplasia (CIN) (squamous intraepithelial lesion [SIL]) and were
      being monitored for recurrence. Of the five cases of atypical glandular cells of
      unknown significance (AGUS), one case had concurrent high grade CIN (SIL).
      Another case was originally misinterpreted as recurrent glandular dysplasia.
      CONCLUSION: Physicians monitoring patients after treatment for CIN need to be
      aware that endometriosis and tuboendometrioid metaplasia may be the source of
      atypical glandular cells and on occasion may be subject to misinterpretation.

PMID- 9018645
TI  - Patterns of uterine activity. Using oxytocin after intracervical PGE2.
AB  - OBJECTIVE: To compare patterns of uterine activity from low-dose oxytocin begun
      immediately or six hours after intracervical placement of prostaglandin E2 (PGE2)
      gel for the induction of labor. STUDY DESIGN: A total of 50 nonlaboring women at
      term with an unfavorable cervix (Bishop score < or = 4) were given a 0.5-mg dose
      of PGE2 gel. Each was then randomized either to be observed or to receive a low
      dose of oxytocin (2 mU/min, increased by 2 mU/min at 30-minute intervals, as
      necessary). After the six-hour observation, the patient was reexamined, and a low
      dose of oxytocin was either begun or continued. An adequate sample size (21 per
      group) was calculated for evaluating uterine activity changes. Comparisons were
      made using chi 2 testing, Student's t test and analysis of variance, as
      appropriate. RESULTS: There were no differences between the two groups in
      maternal race, gestational age, predose Bishop score, predose uterine activity or
      indication for induction. Uterine contractions became more frequent (P < .01) and
      were judged to be more intense (P < .02) and earlier when oxytocin was used
      immediately after PGE2 placement. No uterine hyperstimulation or abnormal fetal
      heart rate pattern was observed that required discontinuation of the oxytocin.
      The percentages of cases delivering vaginally within 24, 36 and 48 hours were
      greater when oxytocin was begun immediately in nullipara (P < .01). CONCLUSION:
      Low-dose oxytocin may be started immediately after instilling intracervical PGE2,
      with shortened time until the onset of adequate contractions.

PMID- 9018646
TI  - Pregnancy outcome. Influence of antiphospholipid antibody titer, prior pregnancy
      losses and treatment.
AB  - OBJECTIVE: To evaluate the effectiveness of combination therapy in preventing
      fetal loss in women with circulating antiphospholipid antibodies and a previous
      history of adverse pregnancy outcomes. STUDY DESIGN: We identified 18 pregnant
      women with antiphospholipid antibodies who had a total of 59 prior pregnancies.
      Of these pregnancies, spontaneous first-trimester abortions occurred in 36
      (61.0%); fetal demise after the first trimester occurred in 9 (15.2%); voluntary
      terminations were elected in seven (11.9%) pregnancies; and there were seven
      (11.9%) surviving infants. During their next pregnancies, these patients were
      treated with prednisone and/or low-dose aspirin. RESULTS: Fourteen patients
      delivered successfully between 33 and 39 weeks' gestation, resulting in a live
      birth rate of 77.8% and a pregnancy loss rate of 22.2%. We also observed an
      association between the number of prior fetal losses, the anticardiolipin
      antibody titer and the fetal survival rate following therapy. Two or more prior
      fetal losses and high autoantibody titer resulted in a fetal survival rate of 50
      75% with varying therapeutic regimens and dosages. However, an improved fetal
      survival rate of 75-100% was observed with less than two prior fetal losses and
      low-mid anticardiolipin antibody titer with the same therapy. CONCLUSION:
      Therefore, the results of this study suggest that although pharmacologic
      prophylaxis improves the outcome of pregnancies complicated by circulating
      antiphospholipid antibodies, such an outcome is influenced by the number of prior
      fetal losses and the anticardiolipin antibody titer.

PMID- 9018647
TI  - Methotrexate. A single agent for early abortion.
AB  - OBJECTIVE: To determine whether methotrexate as a single agent for induced
      abortion in pregnancies up to 5 weeks is as effective, has fewer side effects and
      is as acceptable to subjects as the combination of methotrexate and misoprostol.
      STUDY DESIGN: Women with no greater than a 5-week gestation were compared with a
      historical control group of consecutive women presenting for a medical abortion
      matched for gestational age. Subjects received intramuscular methotrexate on day
      1. The study group received no misoprostol until day 21, when it was offered if
      the abortion had not yet occurred. The control group self-administered one or
      more doses of misoprostol within the first week after methotrexate. A complete
      abortion was defined by either negative transvaginal ultrasound or negative urine
      pregnancy test. All subjects completed a daily symptom log and satisfaction
      questionnaire. The analysis consisted of a comparison of the study group and
      control group for completion and timing of the abortion, symptoms and subject
      satisfaction. RESULTS: There were 40 study subjects and 53 controls. All subjects
      had a medical abortion without surgery. Ten (25%) of the 40 study subjects
      reached study day 21 without bleeding: 4 used misoprostol and 6 chose to wait for
      the abortion to occur spontaneously. One of the 10 subjects had persistent
      embryonic cardiac activity at 21 days and aborted after misoprostol. The mean
      number of days to bleeding was 15.5 days (SD 7.8 days) for the study group as
      compared with 8.1 days (SD 11.3) (P = .0003) for the control group. There was no
      significant difference in the number of days of bleeding, gastrointestinal side
      effects or reported subject satisfaction. CONCLUSION: While methotrexate as a
      single agent was effective in inducing abortion in early pregnancy, 15% of the
      study subjects finally used misoprostol, the abortion took significantly longer,
      and side effects were not less common as compared with those in subjects who
      received the combination of methotrexate and misoprostol.

PMID- 9018648
TI  - Vulvar metastasis of breast carcinoma. A case report.
AB  - BACKGROUND: Metastasis of breast carcinoma to the vulva is rare: only a few cases
      have been previously described. CASE: A 61-year-old woman with a history of
      recurrent breast carcinoma presented with a painless lump on the vulva.
      Excisional biopsy showed an infiltrating adenocarcinoma that was histologically
      similar to the primary breast tumor. CONCLUSION: This report is another of breast
      carcinoma metastatic to the vulva. The clinical features and histologic findings
      distinguish this lesion from a primary breast carcinoma occurring in ectopic
      breast tissue.

PMID- 9018649
TI  - Sexual behaviors and attitudes of geriatric residents in long-term care
      facilities.
AB  - To date, there has been little research focusing upon the sexuality of elders,
      especially those living in long-term care institutions. The present study
      explores the sexual attitudes and behaviors of residents of senior citizens'
      homes. Subjects included 40 residents (17 men and 23 women) from two facilities.
      Subjects completed questionnaires measuring frequency of sexual activity, sexual
      desire, sexual attitudes, and sexual satisfaction. Additional items measured
      ratings of physical and emotional health and perceptions of their residence as
      facilitating or preventing sexual activity. Results indicated that sexual
      activity was infrequent for both males and females. Males reported significantly
      higher levels of sexual desire than did females. Age was negatively correlated
      with solitary sexual desire and with sexual attitudes. Decreased sexual
      satisfaction was associated with perceptions of poor emotional health and lack of
      privacy in the residence. Degree of religiosity was negatively correlated with
      sexual attitudes, and sexual self-efficacy expectations were positively
      correlated with sexual desire. The implications of these findings are discussed
      with respect to quality of life in geriatric residences.

PMID- 9018650
TI  - Identification of social cognitive variables as predictors of safer sex behavior
      and intent in heterosexual college students.
AB  - The purpose of this study was to identify social cognitive factors significantly
      associated with consistent condom use and safer sex intentions for heterosexual
      college students. No or new relationship involvement, positive attitudes toward
      condoms, higher HIV risk perceptions, being male, and being younger were
      associated with more consistent condom use. Higher HIV risk perceptions, positive
      attitudes toward condoms, safer sex negotiation, no or newer relationship
      involvement, lower classification, and higher safer sex perceptions of self
      efficacy were associated with increased intent to engage in safer sex. HIV
      knowledge was not associated with safer sex intent or condom use. HIV
      intervention must go beyond presenting information. Intervention must incorporate
      social cognitive factors associated with safer sex intent and practice into their
      design, targeting groups and building safer sex skills.

PMID- 9018651
TI  - College students' high-risk sexual behavior following alcohol consumption.
AB  - This study is a follow-up to a previous study assessing the relationship of
      alcohol consumption as a disinhibitor to high-risk sexual behavior. Results are
      based on survey data from 1,902 students attending 12 colleges. Sexual behaviors
      occurring after people had "let themselves drink more than normal in order to
      make it easier for them to have sex with someone" were assessed. At least once in
      the past year, 33.2% of the men and 17.4% of the women had met this criterion. In
      those instances, 76.3% of the men and 77.1% of the women initiated condom use for
      vaginal intercourse. Results are discussed in relation to partners' compliance
      following condom initiation and preventing the spread of HIV disease.

PMID- 9018652
TI  - Acknowledging mixed-sex people.
AB  - This article calls attention to the importance of more carefully defining
      femaleness and maleness and more fully acknowledging the existence of mixed-sex
      people. Mixed-sex people are defined as people with at least one female and one
      male characteristic, where female or male characteristics are defined as
      characteristics that are possessed by no more than roughly half the population
      (the distribution criterion) and either play a clear role in reproduction (the
      reproduction criterion) or are very highly correlated across all cultures with
      characteristics that meet both the distribution and reproduction criteria (the
      correlation criterion). Among other recommendations, those who work in the field
      of human sexuality are urged, on the basis of these more careful definitions and
      on ethical grounds, to use the term sex-simplification rather than sex-change in
      describing surgical/hormonal treatments for transsexuals and to radically alter
      their use of the terms heterosexual and homosexual.

PMID- 9018653
TI  - Sexology of ictal masturbation in infancy.
AB  - In 1952, under the title of "Masturbation in Infants," Bakwin reported three
      cases of females all younger than one year of age. Bakwin's type of so-called
      masturbation has been considered in the differential diagnosis of epilepsy in
      several papers published since 1975. The cases reported display a great
      similarity and underscore an ictal explanation of the syndrome.

PMID- 9018654
TI  - Short-term cognitive-behavioral treatment of hypoactive sexual desire in an
      individual with a history of childhood sexual abuse.
AB  - The treatment offered individuals of childhood sexual abuse is often
      unnecessarily long-term and is typically based upon the victimization/recovery
      model. This paper presents a brief case study illustrating the successful short
      term cognitive-behavioral treatment of a 28-year-old woman with hypoactive sexual
      desire who reported a history of repeated sexual molestations throughout her
      childhood.

PMID- 9018655
TI  - Intermittent amantadine for fluoxetine-induced anorgasmia.
AB  - Various drugs, including amantadine, have been reported in the successful
      treatment of antidepressant-induced sexual dysfunction. Only a regular daily
      dosing schedule of amantadine has been used for the treatment of sexual
      dysfunction so far. This case demonstrates that an intermittent dose of
      amantadine at 100 mg five to six hours prior to coitus could be useful in the
      treatment of fluoxetine-induced anorgasmia.

PMID- 9018656
TI  - Tuberculosis screening and anergy in a homeless population.
AB  - BACKGROUND: Tuberculosis has again emerged as a growing public health concern in
      the United States. Among the homeless population, increased risk factors
      contribute to immunodeficiency, which can cause false-negative results on
      purified protein derivative (tuberculin) (PPD) skin testing, the standard
      screening procedure for tuberculosis in individuals. We evaluated the accuracy of
      PPD skin test results by determining anergy status of patients when offering the
      PPD test. METHODS: A consecutive convenience sample of 105 underserved men and
      women were tested at a health clinic located in a homeless shelter in Yonkers,
      NY. These persons were currently homeless, living in a shelter, or formerly
      homeless and using the soup kitchen at the shelter. Three antigens, candidin,
      mumps, and trichophytin, in addition to PPD, were administered intradermally
      using the Mantoux method, and results were read 48 to 72 hours later on the 100
      (95 percent) who returned. An individual was considered to be anergic if the
      delayed-type hypersensitivity reactions were less than or equal to 2 mm for each
      of the four antigens. RESULTS: Of the 100 persons who returned for follow-up, 5
      (5 percent) were found to be anergic. Of these 5, all were previously known to be
      positive for human immunodeficiency virus (HIV). CONCLUSIONS: PPD testing alone
      was found to be an accurate screening test in this population except in those who
      were HIV positive.

PMID- 9018657
TI  - Health and lifestyle issues as risk factors for homelessness.
AB  - BACKGROUND: The objective of this study was to test the hypothesis that there are
      health and lifestyle issues among homeless persons that differentiate them from
      other segments of the population and that can be described as risk factors for
      homelessness. METHODS: This case-control study investigated health and lifestyle
      issues in a panel of patients visiting a health care clinic for homeless persons.
      The same information was collected from a panel of county indigent patients and
      an equal number of privately insured patients enrolled in a nearby academic
      family practice center. RESULTS: We found significant differences among these
      three groups. Differences in health problems were evident, as significantly more
      homeless persons reported mental health, drug and alcohol abuse, and smoking
      problems. There were no differences in the prevalence of other general medical
      conditions as listed by the patients. Homeless persons were younger than the
      control group respondents and more likely to be male, a member of a minority
      group, and unmarried. The childhood experiences of homeless persons were
      distinctive; they were more likely to have lived in a group home or some other
      nonfamily situation, considered themselves to have been delinquent, run away from
      home, been expelled from school, or been placed in reform school. The same held
      true for having been in jail as an adult. They had significantly less education,
      their job experiences were in manual and unskilled arenas, and they were more
      likely to have a gambling problem. A continuum of risk also appeared in that for
      the most part the characteristics and experiences of the indigent group members
      ranked in frequency between those of the homeless and insurance groups.
      CONCLUSIONS: Causes of homelessness appear to be multifactorial. Issues related
      to mental health, alcohol, nicotine, and other drug and substance abuse could be
      responsible for their medical problems, whereas other lifestyle issues might be
      regarded as risk factors for homelessness.

PMID- 9018658
TI  - Local anesthesia for circumcision: which technique is most effective?
AB  - BACKGROUND AND OBJECTIVES: Circumcision is the most commonly performed surgical
      procedure in the United States, and it is painful. Several investigators have
      independently documented the reliability and safety of local anesthesia in
      eliminating the pain associated with circumcision. Investigations have not,
      however, been conducted to determine which technique is most effective in
      reducing the pain of the procedure. This study compares the techniques of local
      anesthesia for circumcision to determine which technique most safely and reliably
      reduces pain. METHODS: Fifty-six infants being circumcised were randomly assigned
      to one of three groups according to anesthesia technique: (1) distal branch
      block, (2) root block, and (3) subpubic block. Change in heart rate and oxygen
      saturation, as well as cry response, were recorded. Heart rate and oxygen
      saturation differences were analyzed utilizing Student's t test, whereas cry
      response was analyzed using the chi-square test. RESULTS: We discontinued using
      the distal branch block technique during the study because we were concerned
      about possible untoward outcomes. As a result, only data from the circumcisions
      of the 42 infants who were assigned to the root block and subpubic block groups
      were analyzed. The dorsal penile nerve root block more reliably reduced the pain
      of circumcision than did the subpubic technique (P = 0.05). There were no serious
      complications with any of the techniques in this study. CONCLUSIONS: Compared
      with distal branch block and subpubic block techniques, nerve block at the penile
      root most reliably and safely eliminated the pain of circumcision.

PMID- 9018659
TI  - Yield of review of systems in a self-administered questionnaire.
AB  - BACKGROUND: Family physicians frequently screen new patients with questionnaires
      that include a standard review of systems. The diagnostic yield of such
      questionnaires is unknown. METHODS: We retrospectively compared results of 248
      patient questionnaires with the clinicians' dictated medical record in a
      university-based family medicine practice. Any positive responses in the review
      of systems section were compared with the medical record to determine whether
      they resulted in a new diagnosis and a therapeutic maneuver. RESULTS: The case
      finding yield for the review of systems section as a whole was 10.5 percent. This
      yield compares favorably with other screening maneuvers in clinical practice.
      Individual questions had yields of 0.0 to 1.6 percent. The positive predictive
      value for a given yes response on the review of systems, defined as new diagnoses
      divided by total yes answers, was 3.3 percent. CONCLUSIONS: Compared with other
      case finding maneuvers in clinical practice, the review of systems questionnaire
      has a very acceptable yield. Its positive predictive value is low, however, and
      there are differences observed among physicians. Certain questions had a positive
      predictive value of 0.0 and could be deleted, which would produce a shortened
      review of systems section.

PMID- 9018660
TI  - The history of the present illness as treatment: who's listening, and why does it
      matter?
AB  - BACKGROUND: The history of the present illness (HPI) is examined as a narrative
      communication that has the potential to be therapeutic. METHODS: The general
      principles that influence the therapeutic potential of the HPI are induced from
      participant observation of personal experience and natural observations of
      conventional social interaction. These principles are corroborated by evidence
      from cross-cultural healing practices, clinical experience, and experimental
      psychology. RESULTS: To facilitate a therapeutic HPI, the clinician should convey
      a sense of safety, sensitivity, affective competence, and cognitive competence.
      Furthermore, the effective clinician joins the patient in coprocessing the
      illness experience. CONCLUSIONS: The (HPI) is not simply a diagnostic
      formulation. When skillfully negotiated, it can be therapeutic because it helps
      patients make cognitive sense of their illness, and it serves as a vehicle for
      sharing the affective burden with the physician. There is therapeutic potential
      in each of the three overlapping operations of the HPI: (1) establishing a
      physician-patient relationship through the process of gathering a database, (2)
      transforming the database into an etiologic narrative, and (3) using the
      narrative to coprocess the experience of illness with the patient. The
      therapeutic potential can be actualized by specific clinical applications.

PMID- 9018661
TI  - Adenocarcinoma of the uterine cervix.
AB  - BACKGROUND: Adenocarcinoma of the uterine cervix is an increasingly common
      cervical neoplasm that has received little attention in the primary care
      literature. The purpose of this paper is to describe an illustrative case that
      provides an excellent opportunity to review the symptoms, diagnostic pitfalls,
      treatment options, and prognosis of this important disease. METHODS: Case report
      is described, along with results of a literature review using MEDLINE and
      pertinent references from retrieved articles. RESULTS: The relative incidence of
      cervical adenocarcinoma has risen from 5 to 10 percent of all cervical neoplasms
      in the 1950s to 10 to 20 percent in recent series. Some studies have also
      reported an increasing absolute incidence linked to widespread oral contraceptive
      use. The diethylstilbestrol-associated clear-cell variant accounts for only 2 to
      3 percent of cases. About 10 percent of patients have only a nonbloody vaginal
      discharge. Cervical adenocarcinoma might be more easily missed on a Papanicolaou
      smear than squamous cell dysplasia and cancer, and it has no characteristic
      colposcopic appearance. The prognosis is excellent with early detection.
      CONCLUSIONS: Family physicians should maintain a high index of suspicion for
      cervical adenocarcinoma when symptoms suggest this disease regardless of
      Papanicolaou smear results.

PMID- 9018662
TI  - Cerebral infarction as multifocal clonic seizures in a term neonate.
AB  - BACKGROUND: The incidence of neonatal stroke in full-term infants has been
      cautiously estimated as 1:10,000, but infants can initially have few symptoms,
      and the condition has the potential for underdiagnosis. Follow-up studies of
      known full-term neonatal stroke victims beyond 3 years of age indicate that most
      develop some form of hemiparesis, seizure disorder, cognitive difficulties, or
      developmental delay during childhood. METHODS: The case of a full-term infant who
      had a left middle cerebral artery infarction and who developed multifocal clonic
      seizures 9 hours after delivery is described and discussed. RESULTS: Head
      sonograms first showed evidence of disease when the infant was 72 hours old.
      Computed tomography (CT) of the head when the infant was 82 hours old showed an
      ischemic infarction in the distribution of the left middle cerebral artery.
      Subsequent magnetic resonance angiography showed a resolving embolus in the left
      middle cerebral artery. CONCLUSIONS: Serial sonograms and CT scans of the
      infant's head, along with magnetic resonance angiography, were useful in making
      the diagnosis of cerebral infarction. A late intrauterine placental
      thromboembolus was the most likely cause. Maternal history of a previous cesarean
      section could be a risk factor. More studies are needed to define the incidence
      of this disease and to describe the risk factors.

PMID- 9018663
TI  - Medical savings accounts: health system savior or insurance scam?

PMID- 9018664
TI  - Atraumatic pneumopericardium in a full-term newborn with fetal tachycardia.

PMID- 9018666
TI  - Of healing and human suffering.

PMID- 9018665
TI  - Endometriosis with massive bloody ascites.

PMID- 9018667
TI  - The predictive value of selected components of medical history taking.

PMID- 9018669
TI  - Placebo response, sustained partnership, and emotional resilience in practice.

PMID- 9018668
TI  - Homelessness and health.

PMID- 9018670
TI  - In utero exposure to medroxyprogesterone.

PMID- 9018671
TI  - Evidence-based medicine and the art of medicine.

PMID- 9018672
TI  - Evidence-based medicine and the art of medicine.

PMID- 9018673
TI  - Mental health patient profile.

PMID- 9018674
TI  - Development of a criteria set and a structured interview for disorders of extreme
      stress (SIDES).
AB  - Data regarding the development of a structured interview measuring alterations
      that may accompany extreme stress are presented. A list of 27 criteria often seen
      in response to extreme trauma and not addressed by DSM-IV criteria for
      posttraumatic stress disorder (PTSD) were generated based on a systematic review
      of the literature and a survey of 50 experts. A structured interview for
      disorders of extreme stress (SIDES) measuring the presence of these criteria was
      administered to 520 subjects as part of the DSM-IV PTSD field trials. Inter-rater
      reliability as measured by Kappa coefficients for lifetime Disorders of Extreme
      Stress was .81. Internal consistency using coefficient alpha ranged from .53 to
      .96. Results indicate that the SIDES is a useful tool for investigation of
      response to extremes stress.

PMID- 9018675
TI  - Anger regulation deficits in combat-related posttraumatic stress disorder.
AB  - We describe a typology of regulatory deficits associated with anger in combat
      related posttraumatic stress disorder (PTSD). Cognitive, arousal, and behavioral
      domain deficits in anger regulation were observed clinically in PTSD patients
      with high levels of anger who were participating in a multi-year trial of a
      structured anger treatment. We also describe a category of patients whose anger
      type we have termed "ball of rage." These patients exhibit regulatory deficits in
      all three domains of anger regulation. We offer a conceptual framework to advance
      the understanding of anger associated with PTSD and to guide its effective
      treatment.

PMID- 9018676
TI  - Trauma-related dissociative states and long-term psychopathology in posttraumatic
      stress disorder.
AB  - Dissociative responses to trauma have been hypothesized to be associated with
      long-term increases in psychopathology. The purpose of this study was to examine
      dissociative responses to premilitary, combat-related and postmilitary traumatic
      events and long-term psychopathology in Vietnam combat veterans with (n = 34) and
      without (n = 28) posttraumatic stress disorder (PTSD). PTSD patients reported
      higher levels of dissociative states at the time of combat-related traumatic
      events than non-PTSD patients. Higher levels of dissociative states persisted in
      PTSD patients in the form of higher levels of dissociative states in-response to
      postmilitary traumatic events. In addition, dissociative responses to combat
      trauma were associated with higher long-term general dissociative symptomatology
      as measured by scores on the Dissociative Experience Scale, as well as increases
      in the number of flashbacks since the time of the war. These findings are
      consistent with previous formulations that dissociation in the face of trauma is
      a marker of long-term psychopathology.

PMID- 9018677
TI  - The relationship between violence dimensions and symptom severity among homeless,
      mentally ill women.
AB  - Little is known about the relationship between violence and symptomatology in the
      lives of homeless, mentally ill women. This study investigates the possibility
      that specific dimensions of violence-frequency, recentness and type-may be
      associated with severity of psychiatric symptomatology in this population.
      Results indicate that each of the abuse dimensions is associated with a broad
      range of psychiatric symptoms and, in combination with substance abuse, account
      for almost one third of the variance in overall distress. These findings suggest
      the possibility that intensity of exposure to violence contributes to the
      severity of psychiatric symptoms even in women who already suffer an overwhelming
      number of intrapsychic and social difficulties; and that multiply traumatized
      women do not become desensitized to the impact of new violence. This article
      discusses the clinical and policy implications of these conclusions.

PMID- 9018678
TI  - The impact of Hurricane Andrew on deviant behavior among a multi-racial/ethnic
      sample of adolescents in Dade County, Florida: a longitudinal analysis.
AB  - Findings from a longitudinal study are presented on the relationships between the
      problems and stresses resulting from Hurricane Andrew and posthurricane minor
      deviant behavior. The sample (N = 4,978) included Hispanic, African-American, and
      White non-Hispanic middle school students enrolled in Dade County, Florida public
      schools. Two waves of data were collected prior to the hurricane; a third was
      obtained approximately 6 months following the storm. Results indicated that
      females were likely to report higher levels of hurricane-related stress symptoms
      than males. After controlling for prehurricane levels of minor deviance, family
      support, and race/ethnicity, hurricane stress symptom level remained a
      significant predictor of posthurricane minor deviant behavior. The findings lend
      support to stress theories of social deviance.

PMID- 9018679
TI  - Alexithymia in Holocaust survivors with and without PTSD.
AB  - Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust
      survivors using the Toronto Alexithymia Scale-Twenty Item Version (TAS-20).
      Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress
      disorder (PTSD) were compared, and associations among alexithymia, severity of
      trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had
      significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS
      20 scores were significantly associated with severity of PTSD symptoms, but not
      with severity of trauma. This study adds to our knowledge of the relationship
      between alexithymia and trauma by demonstrating that this characteristic is
      related to the presence of posttraumatic symptoms and not simply exposure to
      trauma.

PMID- 9018681
TI  - A multimodal, second generation, posttraumatic stress disorder rehabilitation
      program.
AB  - Second Generation posttraumatic stress disorder (PTSD) treatment programs were
      recently proposed as one component of a model of treatment of chronic PTSD. While
      First Generation PTSD programs emphasized trauma work, Second Generation programs
      emphasize skills for the present/future ability to adapt within society. The
      present paper describes a functioning Second Generation PTSD treatment program
      for Vietnam combat veterans. The guiding principles underlying this multimodal
      and vocational rehabilitation program are outlined.

PMID- 9018680
TI  - The validity of posttraumatic stress disorder among Vietnamese refugees.
AB  - The aim of this study was to examine the validity of posttraumatic stress
      disorder (PTSD) among Vietnamese refugees. The study population included 74
      Vietnamese refugees who had resettled in the metropolitan Boston area. The
      previously validated Harvard Trauma Questionnaire was used to assess traumatic
      events and trauma-related symptoms. The number of traumatic events experienced
      was positively correlated with the severity of PTSD-related symptoms in this
      population. Internal consistency estimates and principal components analysis
      provided results that generally supported DSM-IV symptom dimensions of arousal,
      avoidance, and reexperiencing. However, the emergence of two separate dimensions
      of avoidance reflected the important contribution of depression to the traumatic
      response.

PMID- 9018682
TI  - Race, combat, and PTSD in a community sample of New Zealand Vietnam War veterans.
AB  - The association between posttraumatic stress disorder (PTSD), combat exposure,
      and race was examined in a New Zealand community sample of 756 Vietnam War
      veterans. Maori veterans reported higher levels of PTSD than their non-Maori
      counterparts. However, the race effect was shown to be mediated by combat
      exposure level, rank, and combat role. These findings support differential
      experience explanations for the relationship between postwar adjustment and race,
      suggesting that higher levels of psychological symptoms reported by minority
      group veterans can be accounted for by their experience of higher levels of
      combat stressors.

PMID- 9018683
TI  - Preliminary evaluation of sexual problems in combat veterans with PTSD.
AB  - This study evaluated the potential relationship between posttraumatic stress
      disorder (PTSD) and sexual problems. The Golombok Rust Inventory of Sexual
      Satisfaction was mailed to combat veterans currently in treatment at an
      outpatient PTSD clinic. Completed questionnaires were received from 90 patients.
      Results indicated that over 80% of subjects were experiencing clinically relevant
      sexual difficulties. Impotence and premature ejaculation were the most frequently
      reported problems that have corresponding psychological diagnoses. The rates of
      sexual problems for this sample of veterans with PTSD was similar to those
      reported in other studies and exceeded rates of similar problems found in samples
      from community samples. These data suggest that PTSD may be a risk factor for
      sexual problems.

PMID- 9018684
TI  - Posttraumatic stress symptoms in nonexposed, victims, and spontaneous rescuers
      after an avalanche.
AB  - A company from the Norwegian Army was investigated 2 weeks and 4 months after
      they were hit by an avalanche during a winter exercise. The subjects were divided
      into victims, spontaneous rescuers, and nonexposed subjects. The results showed
      that exposed subjects (victims and rescuers) reported higher levels of symptoms
      compared to nonexposed subjects. No differences were found among exposed
      subjects. The level of symptoms was also higher than comparable previous research
      both on victims and professional rescuers or nonprofessionals assigned a role as
      rescuers. All groups showed decrement in symptoms on the 4-month follow-up.

PMID- 9018685
TI  - Posttraumatic stress disorder and substance abuse: use of research in a clinical
      setting.
AB  - The goal of the present investigation was to evaluate whether the process of
      assessing posttraumatic stress disorder (PTSD) in substance abuse/dependence
      inpatients (N = 95) as part of a research protocol influenced the diagnostic
      assessment conducted by clinical staff. The prevalence of current crime-related
      PTSD (CR-PTSD) observed with a research interview was 40% (n = 38), whereas the
      rate of current CR-PTSD documented in (the same) patients' discharge summaries
      was 15% (n = 14). An even lower CR-PTSD prevalence rate of 8% (n = 5) was
      obtained from a new sample of patient discharge summaries (N = 59) collected
      after the cessation of the research project. On chart intake reports, clinical
      staff documented a history of sexual and/or physical assault in approximately one
      half of these patients, but PTSD was not evaluated. PTSD appears to be under
      diagnosed by clinical staff in patients with substance use disorders.

PMID- 9018686
TI  - Wastewater treatment and elimination of pathogens: new prospects for an old
      problem.
AB  - Although the development of wastewater treatment technology is more than one
      hundred years old, most wastewater treatment plants existing today do not
      eliminate pathogens satisfactorily. Even in highly developed nations, receiving
      waters, serving in many cases as drinking water resources, are contaminated with
      pathogens. Surface waters also contain large concentration of phosphate due to
      long lasting wastewater discharges. Cyanobacteria and algal overgrowth is the
      consequence. Present drinking water technology only partially overcomes the
      pollution; it can not be ruled out that drinking water originating from polluted
      resources contains pathogens. This situation frequently goes on unnoticed because
      current indicator organisms are not representative for all pathogens. As studies
      have shown that small concentrations of pathogens also pose a risk for the
      consumer health, this state of affairs is a matter of concern. Microfiltration
      technology is able to significantly eliminate bacteria and protists from
      wastewater. Viruses, although smaller than the pore size of the filters, are
      reduced too because, in wastewater, they are frequently bound to larger
      particles. If the microfiltration of wastewater is preceded by the addition of
      coagulants for the precipitation of phosphate, the precipitate will be retained
      by the filter. The effluent obtained contains very low concentrations of
      phosphate. As viruses also adsorb to the precipitate, the amount of viruses
      eliminated increases and with increasing amounts of coagulant they become
      undetectable.

PMID- 9018687
TI  - Fungal siderophores in plant-microbe interactions.
AB  - Siderophores are low-molecular-weight high specificity, ferric iron chelating
      agents. They are produced under iron starvation by most microorganisms. Systems
      such as siderophores, involved in the acquisition of iron under iron limited
      conditions, may play a major role in microbial interactions. Some siderophores
      are virulence factors in animal and in plant pathogens. Moreover, siderophores
      have been demonstrated to play a major role in plant disease suppression by some
      bacterial biocontrol agents which inhibit the growth or the activity of plant
      pathogens by sequestering iron. This latest type of mechanism has been
      extensively studied in bacteria. However, the role of these iron chelating
      compounds in disease suppression by fungal biocontrol agents has not been clearly
      determined.

PMID- 9018688
TI  - New molecular methods for the detection of hepatitis A and Norwalk viruses in
      shellfish.
AB  - Outbreaks of viral enteric diseases after consumption of shellfish are a major
      health risk. Methodological problems (such as toxicity for cell cultures and low
      viral concentrations) and the unculturability of some strains (i.e. hepatitis A
      virus, Norwalk virus) have made it difficult to study those viruses in the
      environmental samples. Currently, the analysis of the hygienic quality of
      marketable shellfish is determined by the use of fecal indicator bacteria, but
      their reliability in determining viral pollution of shellfish is very low. Recent
      biotechnology developments are providing available rapid, sensitive, and specific
      tools for detecting food-borne viruses in shellfish and in shellfish-growing
      waters. In this paper, a review of these new molecular methods is carried out,
      discussing their advantages and possible applications.

PMID- 9018689
TI  - Monitoring by PCR amplification of the polyphosphate kinase gene added to natural
      water samples.
AB  - A fast, simple method for the detection of the Escherichia coli polyphosphate
      kinase (ppk) gene by means of PCR amplification is described. The method uses
      filters to recover cells from the samples, which makes it suitable for
      environmental studies. The detection of the ppk gene was achieved from samples
      containing 10(2) E. coli cells, either in saline solution or in river water.

PMID- 9018690
TI  - Cellular content of storage inclusions in purple sulfur bacteria determined by
      ultrathin sections.
AB  - Phototrophic sulfur bacteria accumulate storage inclusions as a mechanism to
      adapt to several types of environmental stress. We compare the content of
      elemental sulfur and poly-beta-hydroxybutyrate (PHB) found in cultures growing
      under laboratory conditions with the content found in microorganisms in natural
      environments. Since natural communities are extremely heterogeneous in
      composition (they do not contain only phototrophic sulfur bacteria) and
      physiological state, it was not possible to apply conventional chemical analyses
      for the determination of the contents of sulfur and PHB. The study was performed
      by means of transmission electron microscopy, which turned out to be an excellent
      tool for this purpose. The results indicate that, in natural environments, cells
      have an extremely high content of storage inclusions, much higher than their
      laboratory grown counterparts, probably as a consequence of less favorable
      environmental conditions.

PMID- 9018691
TI  - Free-living spirochetes from Cape Cod microbial mats detected by electron
      microscopy.
AB  - Spirochetes from microbial mats and anaerobic mud samples collected in salt
      marshes were studied by light microscopy, whole mount and thin section
      transmission electron microscopy. Enriched in cellobiose-rifampin medium,
      selective for Spirochaeta bajacaliforniensis, seven distinguishable spirochete
      morphotypes were observed. Their diameters ranged from 0.17 micron to > 0.45
      micron. Six of these morphotypes came from southwest Cape Cod, Massachusetts:
      five from Microcoleus-dominated mat samples collected at Sippewissett salt marsh
      and one from anoxic mud collected at School Street salt marsh (on the east side
      of Eel Pond). The seventh morphotype was enriched from anoxic mud sampled from
      the north central Cape Cod, at the Sandy Neck salt marsh. Five of these
      morphotypes are similar or identical to previously described spirochetes
      (Leptospira, Spirochaeta halophila, Spirochaeta bajacaliforniensis,
      Spirosymplokos deltaeiberi and Treponema), whereas the other two have unique
      features that suggest they have not been previously described. One of the
      morphotypes resembles Spirosymplokos deltaeiberi (the largest free-living
      spirochete described), in its large variable diameter (0.4-3.0 microns),
      cytoplasmic granules, and spherical (round) bodies with composite structure. This
      resemblance permits its tentative identification as a Sippewissett strain of
      Spirosymplokos deltaeiberi. Microbial mats samples collected in sterile Petri
      dishes and stored dry for more than four years yielded many organisms upon
      rewetting, including small unidentified spirochetes in at least 4 out of 100
      enrichments.

PMID- 9018692
TI  - Purification and properties of beta-galactosidase from Aspergillus nidulans.
AB  - Beta-Galactosidase from mycelial extract of Aspergillus nidulans has been
      purified by substrate affinity chromatography and used to obtain anti-beta
      galactosidase polyclonal antibodies. A. nidulans growing in lactose as carbon
      source synthesizes one active form of beta-galactosidase which seems to be a
      multimeric enzyme of 450 kDa composed of monomers with 120 and 97 kDa. Although
      the enzyme was not released to the culture medium, some enzymatic activity was
      detected in a cell-wall extract, thus suggesting that it can be an extracellular
      enzyme. Beta-Galactosidase of A. nidulans is a very unstable enzyme with an
      optimum pH value of 7.5 and an optimum temperature of 30 degrees C. It was only
      active against beta-galactoside substrates like lactose and p-nitrophenyl-beta-D
      galactoside (PNPG).

PMID- 9018694
TI  - New contributions to the wall polysaccharide structure of vegetative mycelium and
      fruit body cell walls of Agaricus bisporus.
AB  - Significant differences in chemical composition and structure of wall
      polysaccharides were found in Agaricus bisporus vegetative mycelium in comparison
      with the fruit body mycelium. Chemical fractionation of the walls demonstrated
      distinct percentages of the successively solubilized polysaccharides in both
      walls, and different proportions of their respective sugar monomers.
      Permethylation of isolated fractions also showed striking differences relative to
      the sugar linkages between the two types of walls studied. Furthermore, infrared
      spectrophotometry exhibited a distinct polysaccharidic configuration in several
      fractions. All the described differences were correlated with the transition of
      vegetative mycelial walls to the fruiting stage of differentiation.

PMID- 9018693
TI  - Effect of nutrients on alginate synthesis in Azotobacter vinelandii and
      characterization of the produced alginate.
AB  - The role of nutrients on alginate production by Azotobacter vinelandii was
      studied in batch cultures. The largest amount of bacterial alginate was obtained
      in presence of: 0.3 g/l MgSO4.7H2O. 0.4 g/l NaCl, 42 mg/l CaCl2.2H2O,.4 mg/l
      KH2PO4, 16 mg/l K2HPO4, 2.5 mg/l FeSO4.7H2O, 2.9 mg/l H3BO3, 2 mg/l ZnSO4.7H2O, 2
      mg/l Na2MoO4.2H2O, 0.3 mg/l CuSO4.5H2O, 0.2 mg/l MnCl2.4H2O. Alginate production
      was not enhanced by natural additives or inducing agents, except for acetate,
      which increased alginate yield. The pure alginate contained 0.36% ash and 0.4%
      protein. It is similar to algal alginate, but it has an extra acetyl group. It
      contains 69.5% M-M block, 27.5% M-G block and 3% G-G block.

PMID- 9018695
TI  - Epidemiological markers of Serratia marcescens isolates causing nosocomial
      infections in Spain (1981-1991).
AB  - The distribution of epidemiological markers (serotyping and phage-typing) of
      Serratia marcescens isolates from nosocomial episodes (63 nosocomial cutbreaks
      with 475 isolates, and 1208 sporadic cases) received in our laboratory during the
      period 1981-1991 was studied. The records for 1683 isolates from Spanish
      hospitals have been analyzed. In relation with the sporadic cases, the
      predominant types were serotype O6 (13.4%) and serotype O14 (11.4%);
      polyagglutinable strains accounted for 15.6%; in outbreaks, type O14 is clearly
      predominant (27.4%). Phage-typing was a good secondary marker, with a 87.9% of
      typability; the number of lytic patterns was very high, extended patterns (six or
      more phages) being the most frequent. We have studied the characteristics of S.
      marcescens isolates causing infections in the nosocomial environment in Spain.

PMID- 9018697
TI  - Positive temporal sharp waves in electroencephalograms of the premature newborn.
AB  - Positive temporal sharp waves (PTS) were studied in electroencephalograms (EEG)
      of 92 premature infants born either at 31 and 32 weeks of gestational age,
      recorded during the first week of life. The infants were assigned either to a
      reference group (asymptomatic) or to one of three pathologic groups (neonatal
      asphyxia, hypoglycemia or hypocalcemia, or periventricular leukomalacia with
      rolandic positive sharp waves). Regardless of the group, no significant
      differences in PTS criteria (morphology, frequency, amplitude, duration and
      lateralization) were found between 31- and 32-week infants. The PTS observed in
      55% of the asymptomatic infants were characterized by low frequency (0.13 +/-
      0.12/min), a mean amplitude of 109.8 +/- 25.8 microV and a mean duration of 148.7
      +/- 35.4 ms. For PTS recorded in 72 to 75% of pathologic infants, mean duration
      and amplitude were significantly greater in all groups than in asymptomatic
      infants, whereas frequency was significantly greater only in the group presenting
      with asphyxia. Discriminant analysis based on the three PTS criteria (frequency,
      amplitude and duration) allowed correct classification for only 30 to 54% of
      infants in the four groups. The frequency of PTS decreased rapidly during the
      second week of life in asymptomatic infants, but persisted in a larger number of
      infants in the pathologic groups. This study shows that PTS have no negative
      significance when they are few in number, short in duration, moderate in
      amplitude and rapidly regressive, thus probably reflecting the vulnerability of
      the temporal lobe during the traumatic period of birth. However, they require
      attention when they are abundant and/or slow, ample or tend to persist. They may
      thus constitute a nonspecific response to injury to an immature brain.

PMID- 9018696
TI  - In vitro activity of fluconazole on Candida albicans.
AB  - Fluconazole is a triazole antifungal compound suitable for the treatment of
      fungal infections, including those caused by Candida albicans. Fluconazole, as
      all azole antifungals, is a potent inhibitor of ergosterol biosynthesis. The aims
      of this study are to evaluate the susceptibility of C. albicans strains isolated
      from clinical specimens against fluconazole, and to assess the decrease in
      ergosterol produced on these strains when they are incubated in vitro with this
      antifungal compound. Sixty six yeast strains were isolated and identified from
      vaginal specimens of 710 women of a tocogynecology surgery (9.3%), C. albicans
      being the most frequent species (n = 52, ca. 79%). An agar dilution technique was
      used to determine the minimal inhibitory concentration (MIC) of fluconazole for
      the C. albicans strains. The MICs rank was between 1 and 20 micrograms/ml (mean =
      6.6 micrograms/ml). Ergosterol content from ten C. albicans strains (MIC for
      fluconazole = 5 micrograms/ml) was assessed using the method proposed by Breivik
      and Owades, with three concentrations of fluconazole (2.5, 5 and 20
      micrograms/ml) and four contact times (1, 6, 12 and 24 h), in comparison to no
      treated strains (control). The mean content of ergosterol was lower in the
      treated strains than in the control ones, and became statistically significant
      after 12 h of incubation.

PMID- 9018698
TI  - Newborns with hyperbilirubinemia: usefulness of brain stem auditory response
      evaluation.
AB  - We describe brain stem auditory evoked potentials (BAEP) obtained in 48 full-term
      newborns (20 boys, 28 girls) presenting with high serum total bilirubin
      concentration (from 238 to 442 mM) without Rhesus of group A, B, O factors
      incompatibility. Recordings were performed on the 3rd day of life and repeated 5
      7 days post-appropriate therapy with photostimulation and exchange transfusion
      (when bilirubin concentration had decreased below 136 mM). Supplementary
      recordings were performed 3, 6 and 12 weeks later in order to assess test-retest
      reliability of components. Mean values of BAEP latencies were compared with those
      obtained in 40 age-matched control subjects using the same recording procedures.
      At first recording session (on the 3rd day), latencies of waves III and V
      obtained in hyperbilirubinemic patients were significantly increased as compared
      with records in control subjects. Recordings performed 5 to 7 days post-therapy
      and during subsequent recording sessions showed no significant differences
      between patients and control groups. Serial neuropsychological evaluations
      obtained over a 3-year follow-up showed no subsequent neurodevelopmental
      abnormality for all patients. These findings suggest that hyperbilirubinemia can
      alter central neurotransmission in auditory brain stem pathways, but this
      modification is only transient.

PMID- 9018699
TI  - Body temperature regulation in the newborn infant: interaction with sleep and
      clinical implications.
AB  - Thermoregulation in newborn infant differs from that of adult. Comparisons
      between sleep stages show that, during rapid eye movements (REM) sleep, the
      impairment of thermoregulatory responses in adult is not observed in newborn.
      Both behavioral and autonomic temperature regulations are always operative in the
      range of air temperatures usually imposed. The interaction between sleep and
      thermoregulation seems to be less important in newborns than in adults,
      suggesting that sleep processes are well protected, reducing the probability of
      occurrence of central dysfunction. According to the model describing
      thermoregulation during sleep on the basis of changes in the hierarchical
      dominance of brain structures, either the influence of diencephalic structures is
      never depressed in REM sleep or the functional autonomy of the rhombencephalon is
      still relevant in the immature encephalon of the newborn. The thermoregulatory
      model also allows understanding of inter-individual differences in
      thermoregulation and levels of thermoneutrality. An attempt has also been made to
      learn the role of heat stroke in the production of sudden infant death syndrome
      when body heat loss is hampered.

PMID- 9018700
TI  - Heart rate changes during sleep in normal two-month-old infants.
AB  - Thirty-five normal two-month-old infants had nighttime followed by daytime
      polygraphic recordings. Heart rates were calculated every minute in active and
      quiet sleep states. A difference in mean heart rates was found between the two
      states and between the two recordings. Rates were lower at night than during the
      day (P < 0.0001), regardless of the sleep state. During nighttime or daytime
      recordings as a function of sleep cycles or during sustained sleep episodes,
      heart rates were minimal in the middle of recordings, but differences were
      statistically significant for only a few results (mainly in QS). Intrasleep
      awakening led to a marked increase in heart rate after sleep was resumed,
      although differences were only statistically significant when the awakened infant
      was fed. Infants with episodes of periodic breathing had lower mean heart rates
      throughout the recordings, but differences were not statistically significant.
      Respiratory and heart rates showed similar changes during the recordings, and a
      statistically significant correlation was found between the two measurements.

PMID- 9018701
TI  - The trigeminal complex. Anatomy and physiology.
AB  - The many procedures performed for the treatment of trigeminal neuralgia require
      an extensive knowledge of the brainstem and spinal nuclei anatomy and physiology,
      their projections, central and peripheral connections, the trigeminal autonomic
      elements, and autonomic effects of trigeminal injury. Recent advances in the
      understanding of the anatomy and physiology complex as presented in the
      neuroscience literature are reviewed.

PMID- 9018702
TI  - Microvascular decompression for trigeminal neuralgia. Surgical technique and long
      term results.
AB  - In summary, it can be concluded that MVD has a long-term success rate equal or
      superior to percutaneous procedures without the higher rate of permanent
      neurologic sequelae. It is a safe operation with an almost negligible mortality
      and low morbidity in skilled hands. If the goal in the treatment of TGN remains
      obtaining a pain-free state without the need for medication and no permanent
      neurologic deficit, then MVD remains the definitive procedure of choice for
      typical TGN.

PMID- 9018703
TI  - Treatment of trigeminal neuralgia by percutaneous radiofrequency rhizotomy.
AB  - Percutaneous radiofrequency rhizotomy (PSR) is recognized as a simple, effective,
      and safe surgical treatment for trigeminal neuralgia. Rates of pain recurrence
      after PSR are the lowest versus those of other percutaneous procedures, and
      similar to those of microvascular decompression.

PMID- 9018704
TI  - Radiofrequency treatment of trigeminal neuralgia using a cordotomy-type
      electrode. A method.
AB  - A specific technique for treating trigeminal neuralgia with radiofrequency
      thermocoagulation uses a small electrode which allows the lesion to be made
      behind the ganglion in the retro gasserian rootlets where little pain is produced
      and the patient can be treated while awake. On-line monitoring during the
      lesioning with this electrode permits accurate control over the location and
      extent of the numbness in the face. This technique yields a very high incidence
      of patient satisfaction and a very low incidence of annoying dysesthesias in the
      face and corneal sensory loss.

PMID- 9018705
TI  - Percutaneous balloon compression of the trigeminal nerve.
AB  - Balloon compression is a simple and effective percutaneous approach for the
      treatment of classic trigeminal neuralgia or trigeminal neuralgia secondary to
      multiple sclerosis. The operation injures large myelinated fibers, removing the
      "trigger" to the presumed ephaptic transmission of pain. Because unmyelinated
      fibers, which mediate the corneal reflex, are preserved, compression may be of
      advantage in the treatment of first division pain, since the corneal reflex is
      mediated by the small unmyelinated fibers. In the author's series of 141
      consecutive patients treated by balloon compression, overall recurrence rate was
      26%, with 80% of patients experiencing mild numbness postoperatively.

PMID- 9018706
TI  - Percutaneous retrogasserian glycerol rhizotomy. Current technique and results.
AB  - Despite the establishment of the vasculoneural compression as a frequent cause of
      trigeminal neuralgia, minimally invasive surgical techniques to treat medically
      refractory trigeminal neuralgia are needed in order to minimize the risks
      associated with craniotomy. Percutaneous retro gasserian glycerol rhizotomy
      (PRGR) is one of the alternative surgical treatments to microvascular
      decompression. Technical simplicity, less chance of trigeminal sensory loss, no
      need of intraoperative sensory testing, and no attempted deliberate destruction
      of the trigeminal nerve are advantages over other percutaneous trigeminal
      operations.

PMID- 9018707
TI  - Leksell Gamma Knife treatment of tic douloureux.
AB  - Stereotactic radiosurgery with the Leksell Gamma Knife under local anesthesia can
      effectively treat patients with recurrent tic douloureux after unsuccessful
      medical/surgical procedures. Eight of 12 patients have shown complete relief or
      improvement of their trigeminal neuralgia after 3 to 4 year follow-up. No
      complications have been observed, with the exception of 1 patient who developed a
      small area of radionecrosis in the medial temporal lobe.

PMID- 9018708
TI  - Gamma knife radiosurgery for trigeminal neuralgia.
AB  - Radiosurgery is one of the surgical treatments of trigeminal neuralgia. Through
      precise irradiation of the proximal trigeminal nerve identified on high
      resolution imaging, pain relief can be achieved after a short latency interval.
      This image-guided approach has been useful for both patients with persistent pain
      after other surgeries, and as a primary surgical option. A minimum dose of 70 Gy
      delivered with the gamma knife has been associated with low risk for facial
      numbness, and no other morbidity. Management of trigeminal neuralgia without an
      incision, transfacial needle placement or nerve section may prove useful to
      increasing numbers of patients.

PMID- 9018709
TI  - Atypical facial pain and other pain syndromes. Differential diagnosis and
      treatment.
AB  - Knowledge of each differential diagnosis of prosopalgia is important to any
      neurosurgeon who treats facial pain. Pain control is possible with treatment
      specific to the diagnosis, including those forms of facial pain known to be the
      most difficult to treat. An outline for the management of atypical facial pain,
      anesthesia dolorosa, and postherpetic neuralgia is presented with a review of the
      correlative anatomy for each surgical procedure.

PMID- 9018710
TI  - Pregnancy outcome investigation for the 21st century.

PMID- 9018711
TI  - Data linkage methods used in maternally-linked birth and infant death
      surveillance data sets from the United States (Georgia, Missouri, Utah and
      Washington State), Israel, Norway, Scotland and Western Australia.
AB  - In this paper we describe the methods used to link birth and infant mortality and
      morbidity surveillance data sets into sibships using deterministic or multistage
      probabilistic linkage methods. We describe nine linked data sets: four in the
      United States (Georgia, Missouri, Utah and Washington State), and four elsewhere
      (Scotland, Norway, Israel and Western Australia). Norway and Israel use
      deterministic methods to link births and deaths into sibships. The deterministic
      linkage is usually dependent on the availability of national identification
      numbers. In both countries they assign these numbers at birth. Deterministic
      linkage is usually highly successful, and the major problem is the validation of
      linkages. In the United States, Western Australia and UK linkage is multistage
      and probabilistic. This approach is usually dependent on the calculation linkage
      weights from sociodemographic variables. The success rates of probabilistic
      methods are above 80%. Maternally-linked perinatal data open new vistas for
      epidemiological research. Recurrence of poor perinatal outcomes is more
      appropriately studied using longitudinally-linked data sets. In addition, the
      emergence of risk factors and the recurrence of risk factors can be studied.

PMID- 9018712
TI  - The Israeli Maternal Perinatal Database: methods and preliminary evaluation.
AB  - The Israel Maternal Perinatal Database (IMPD) includes the 1980-92 birth cohorts
      and was created using deterministic linkage, based on a unique identity number.
      This number is assigned at birth for Israeli-born infants and upon acquiring
      permanent or temporary residential status for immigrants and is used widely. The
      IMPD includes approximately 1.3 million births and about 400,000 mothers with
      more than one birth, 40,000 mothers with more than three births and 20,000 grand
      multipara mothers with four births or more. The pretest-based estimates of
      incorrectly matched births are 2%. The expected percentage of underlinkage is 5
      10% for births occurring before 1985. Since 1985, incorrect maternal
      underlinkages result only when a birth occurs out of Israel to an Israeli
      resident. One of the advantages of the IMPD is the ability to estimate linkage
      reliability, validity and censoring effects by comparison with an external data
      sources, the National Population Register, which groups each mother with all her
      living children under the age of 18 years. One of the potential analysis pitfalls
      is the effect of censoring at entry as a result of influx of immigrants from the
      former Soviet Union and Ethiopia.

PMID- 9018714
TI  - Does changing paternity contribute to the risk of intrauterine growth
      retardation?
AB  - An immune reaction initiated by paternal antigens may be necessary for healthy
      placental development, pregnancy maintenance and infant growth. An inadequate
      immune response may result in intrauterine growth retardation (IUGR). We
      hypothesised that a change in paternity may interfere with the immune response
      and cause poor placentation with resultant IUGR. In this paper we examine the
      risk of IUGR associated with changes in paternity. We used the Utah Successive
      Pregnancies Data Set that contains information on women across their pregnancies.
      We restricted the analysis to 141,817 women with two or three pregnancies. Women
      who did not have an IUGR infant in the previous pregnancy were at a 20-30%
      greater risk of developing IUGR if they had changed partners. Women who had a
      previous IUGR infant were at no increased risk for IUGR after a change in
      paternity. These results may point to an immune mechanism or may be as a result
      of residual confounding of unmeasured risk factors for IUGR. Further studies with
      data that contain more sociodemographic and biological risk factors for IUGR are
      necessary to exclude residual confounding.

PMID- 9018713
TI  - The association of change in maternal marital status between births and adverse
      pregnancy outcomes in the second birth.
AB  - The relationships between change in marital status between two consecutive births
      and adverse pregnancy outcomes at the second birth were investigated using linked
      Washington State 1980-93 white singleton birth certificates. Women who were
      married at the first birth had lower low birthweight (LBW) and small-size-for
      gestational-age (SGA) rates at that birth than single women, and women married at
      the second birth had lower LBW, SGA and preterm delivery rates at that birth
      regardless of marital status at the first birth. Adjusted relative risks (RR) of
      LBW and SGA were significantly increased for initially married women who were
      single at the second birth compared with those who remained married (RR = 1.4 and
      1.3, respectively). Risks of LBW and SGA were significantly decreased among
      initially single women who married by the second birth, compared with those
      remaining single (RR = 0.7 for LBW and 0.8 for SGA). We conclude that the largely
      unstudied subgroup of previously married women is at increased risk for adverse
      pregnancy outcomes. Public health policy and programmes directed at high-risk
      mothers and infants should be aware of the specific physical and emotional needs
      of this group of child-bearing women.

PMID- 9018715
TI  - The relationship of interpregnancy interval to infant birthweight and length of
      gestation among low-risk women, Georgia.
AB  - To examine the association between interpregnancy interval and low birthweight (<
      2500 g), preterm delivery (< 37 weeks' gestation), and inadequate fetal growth,
      we studied a population-based sample of 23,388 white and 4885 black women at low
      risk for adverse pregnancy outcomes who delivered their first and second infants
      in Georgia from 1980 to 1992. We used fetal death and livebirth certificates. The
      interpregnancy interval was the time from delivery to the woman's next
      conception. For each pregnancy outcome, we stratified by race and used logistic
      regression to assess the association between interpregnancy interval and outcome,
      while controlling for confounders. Intervals < 6 months were observed for 3.7% of
      white women and 7.0% of black women and intervals > or = 48 months were seen for
      16.8% of white women and 24.8% of black women. Results from logistic regression
      showed that, for both races, interpregnancy interval was associated with low
      birthweight and preterm delivery. Nearly all of the increased risk occurred in
      intervals < 6 months or > or = 48 months. The magnitude of the increase in risk
      associated with these intervals ranged from modest to moderate and was similar
      for black and white women. Because short interpregnancy intervals are rare and
      are weak risk factors among low-risk women, efforts to lengthen interpregnancy
      intervals are unlikely to reduce substantially their rates of adverse pregnancy
      outcomes.

PMID- 9018716
TI  - Attempt and success rates for vaginal birth after caesarean section in relation
      to complications of the previous pregnancy.
AB  - The relationships between prior obstetrical complications and subsequent trial of
      labour and vaginal birth after Caesarean (VBAC) success likelihood were examined
      among a cohort of Washington State women with a first livebirth via Caesarean
      delivery and a second livebirth between 1987 and 1993 (n = 10110). Overall, 64%
      of the cohort undertook a labour trial, and 62% of those who attempted VBAC
      delivery were successful, for an overall VBAC rate of 40%. Women with fetal
      macrosomia, cephalopelvic disproportion, prolonged labour, diabetes, or placental
      problems in the first pregnancy were less likely to undergo a labour trial in the
      second pregnancy than those without these factors, while women with prior induced
      labour, genital herpes, fetal distress, or breech presentation were more likely
      to attempt vaginal birth. Approximately half of women with prior macrosomia,
      labour problems, or chronic medical conditions who attempted VBAC succeeded, as
      did three-quarters of women with prior breech presentation or placental
      conditions. Overall VBAC rates were around 33% for women with previous fetal
      macrosomia, labour problems, or chronic medical conditions, and 45-55% among
      those with herpes, fetal distress or breech presentation at the first birth.
      Trial of labour should especially be encouraged among women without prior labour
      problems.

PMID- 9018717
TI  - Smoking during pregnancy: Missouri longitudinal study.
AB  - Maternal smoking during pregnancy has been shown to be associated with reduced
      birthweight and increased fetal and infant mortality. This paper examines these
      patterns in first and second maternally-linked singleton pregnancies from 1978 to
      1990 among 176,843 Missouri resident women with known smoking status in both
      pregnancies. Generally women were more likely to smoke in their second
      pregnancies (27.4%), than in their first (25.8%). This pattern was strongest
      among those whose first pregnancies occurred as teenagers, and for black women.
      The relationships of smoking during the first and second pregnancies to outcomes
      in the second pregnancies were examined primarily through multivariate logistic
      regression. The adjusted relative risk (RR) of low birthweight (< 2500 g) in the
      second pregnancy to not smoking in either pregnancy was 1.82 for those who smoked
      during the second pregnancy only, and 1.87 for those who smoked in both
      pregnancies. For those who smoked in the first pregnancy only, the RR was 0.97,
      not significantly different from 1. Adjusted smoking RRs for small-for
      gestational age were larger, while adjusted RRs for fetal and neonatal mortality
      were smaller than the smoking RRs for low birthweight.

PMID- 9018718
TI  - Maternal smoking, birthweight and gestational age in sudden infant death syndrome
      (SIDS) babies and their surviving siblings.
AB  - To evaluate the effect of maternal smoking on intrauterine growth of babies who
      died of sudden infant death syndrome (SIDS), birthweights of SIDS infants and
      their surviving siblings were compared with birthweights of infants in sibships
      were all infants survived the first year of life. We studied 184,349 mothers with
      at least two births registered in the population-based Swedish Medical Birth
      Registry during 1983-91. The mother being the unit of analysis, birthweight and
      gestational age of her infants were the repeated measures used in a repeated
      measures analysis of variance. Mothers whose first two infants survived at least
      1 year, smoked less than mothers of SIDS infants, 25 and 41% (P < 0.01). Overall,
      SIDS mothers did not smoke more while pregnant with the SIDS infant than while
      pregnant with the surviving sibling. SIDS siblings weighted, on average, 90 g
      less than infants in non-affected sibships. SIDS babies were even lighter, 193 g,
      and had 3.8 days shorter mean gestational age, compared with same birth-order
      babies in non-affected sibships. After adjustment for gestational age, the
      birthweight difference changed only slightly for SIDS siblings, while the
      difference for SIDS infants was reduced from 193 to 110 g. Further adjustment for
      smoking reduced the birthweight difference for SIDS siblings, from 74 to 50 g,
      and SIDS infants, from 110 to 82 g. Intrauterine growth retardation of sibships
      with a SIDS baby is explained only partly by maternal smoking. The even lower
      birthweight of the SIDS baby, resulting from shorter gestational age, cannot be
      explained by smoking, suggesting pregnancy factors specific to the SIDS baby and
      not to its siblings.

PMID- 9018719
TI  - Risk factors for the recurrence of premature rupture of the membranes.
AB  - Premature rupture of the amniotic membranes (PROM) occurs in up to 20% of all
      births. Although many studies have examined risk factors for PROM and, in
      particular, preterm PROM (PPROM, if less than 37 weeks' gestation), the aetiology
      of PROM recurrence has not been examined as closely. This study investigated
      factors that may increase the risk of PROM among women who have already
      experienced one PROM birth. Maternally linked Washington State birth certificates
      from 1984 to 1993 identified 208 women with consecutive PROM births. Controls
      were a random sample (n = 848) of women who had one birth on record complicated
      by PROM, but whose subsequent birth was not. Among women with a prior term PROM,
      increased risk for PROM recurrence (term PROM or PPROM) was associated with an
      intervening fetal death at less than 20 weeks' gestation (OR = 2.4, 1.3-4.5) and
      with parity of two or more (OR = 2.0, 1.3-3.4). None of the factors assessed
      significantly increased the risk of recurrence of PROM (term PROM or PPROM) among
      women with a prior PPROM. Other potential risk factors for PROM recurrence were
      evaluated within the two PROM groups (PPROM or term PROM at first birth) by
      stratifying among the cases according to gestational length at subsequent birth.

PMID- 9018720
TI  - Risk of recurrence of birth defects in Washington State.
AB  - A population-based study was conducted using maternally-linked birth certificate
      records from Washington State for 1980-93 to evaluate the risk of birth defect
      occurrence among infants with previously affected siblings, relative to infants
      whose siblings did not have birth defects. The risks of recurrence of similar and
      dissimilar defects were estimated, and the effects of change in paternity and/or
      city of residence were evaluated as proxies of genetic and environmental effects.
      At the first birth on record, 3322 women were identified in the linked
      certificates as giving birth to a child with a birth defect; 6620 women whose
      first birth did not result in an infant with a defect were randomly selected for
      comparison. Women with a malformed infant had an increased risk of having a
      malformed infant at the subsequent birth (Relative Risk = 1.9, [95% Confidence
      Interval (CI) = 1.5-2.4]), which did not vary by intervening changes in partner
      or residence. The risk of recurrence of the same general type of defect [RR =
      11.7, 95% CI = 9.7-19.50] was much greater than that of occurrence of a
      dissimilar defect [RR = 1.5, 95% CI = 1.1-1.9]. This was consistent for all
      defect categories, and did not vary markedly by changes in partner or residence.

PMID- 9018721
TI  - Factors associated with repetition of low birthweight: Missouri longitudinal
      study.
AB  - The tendency to repeat low birthweight (LBW < 2500 g) was studied in 182,285
      linked first and second birth Missouri livebirths for 1978-90, of which 10,701
      had first birth LBW. We examined the likelihood of LBW repetition by first birth
      birthweight, preterm delivery, and small-for-gestational-age (SGA) status by
      race, and the odd ratios (ORs) of repeat LBW for risk factors such as smoking, in
      comparison with ORs of second birth LBW among women with normal-weight first
      births. We found a strong tendency to repeat LBW (21%), especially following more
      extreme LBW first births. Adjusted ORs for repeat LBW were 10.1 for births that
      were preterm and SGA; 7.9 for preterm non-SGA; and 6.3 for SGA term births.
      Significant ORs of LBW repetition were found for smoking (1.52 and 1.85 for
      smoking in second pregnancy only and both pregnancies, respectively), short
      interpregnancy interval (1.33), and advanced maternal age (1.17), but the ORs
      were generally lower than those for women with normal-weight first births. Low
      pre-pregnancy weight was a significant risk factor for LBW repetition.

PMID- 9018722
TI  - Adolescent age at first pregnancy and subsequent obesity.
AB  - Adolescent pregnancy has been associated with subsequent obesity. This paper
      examines the patterns of obesity for second and third pregnancies among women who
      had their first singleton pregnancy as teenagers. We used maternally-linked data
      from 1978 to 1990 among 43,160 Missouri resident women. Age, parity,
      interpregnancy interval and prior body mass index were significantly associated
      with subsequent obesity among adolescents. Race, marital status and smoking had
      significant interactions with age. Among older women, being African-American and
      never having married was associated with an increased probability of obesity, and
      smoking had a greater effect on obesity at higher maternal age. Race and marital
      status did not have significant effects on obesity among younger women. The most
      important predictor of obesity was prior body mass index. Body mass index before
      the first pregnancy had a greater effect on subsequent obesity if the intervening
      interpregnancy weight gains were large. Excessive weight gain during pregnancy
      presents the health care provider with a dilemma. An increase in birthweight
      associated with high prenatal weight gains may diminish the risk of infant
      mortality and morbidity in an index pregnancy, but subsequent obesity may
      increase perinatal mortality rates, the rates of obstetric problems and neural
      tube defects.

PMID- 9018723
TI  - Childhood influences on adult health: a review of recent work from the British
      1946 national birth cohort study, the MRC National Survey of Health and
      Development.
AB  - Research in this study has shown that growth in utero and early-life development
      were associated with a range of adult outcomes, including blood pressure,
      respiratory function and schizophrenia. It has also been shown that childhood
      social and educational factors are strongly associated with adult mental and
      physical health, and with adult health-related behaviour. It is suggested that
      the observed long-term effects of early-life physical development do not
      represent an inevitable outcome of childhood development, but one which is
      mediated by the chain of social factors that also begins in early life. The
      conclusions emphasise that since the social and economic circumstances that
      affect child health have changed greatly in recent years in some ways which are
      particularly adverse, we need now to be aware of the implications of such change
      not only for the health of children today, but also for their health in
      adulthood.

PMID- 9018724
TI  - Fumes from the spleen.

PMID- 9018725
TI  - The relationship between maternal birthweight and gestational age in twins and
      singletons and those of their offspring in Norway.
AB  - In order to elucidate whether maternal plurality affects offspring intrauterine
      growth, the relationship between birthweight and gestational age of twins and
      singletons and those of their first singleton liveborn children in Norway was
      studied using data from the Medical Birth Registry. The population-based sample
      consisted of 49,698 mother-offspring pairs (48,842 with singleton and 856 with
      twin-mothers). In bivariate analyses, no significant differences in mean
      birthweight and gestational age of offspring of twin and singleton mothers were
      found, although the mean birthweight and gestational age of the twin-mothers
      themselves were significantly lower than those of singletons (819 g and 14 days
      respectively). In multiple regression analysis, the expected birthweight of
      offspring was 230.3 g (95% CI: 193.2-267.4 g) higher when the mother was a twin
      than when the mother was a singleton, when controlling for non-standardised
      maternal birthweight. When adjusting for relative maternal birthweight (z-score),
      the association between maternal plurality and offspring birthweight was not
      statistically significant. The results suggest that being born as a twin has no
      substantial consequences on offspring growth in utero and show that mean
      differences in birthweight between twins and singletons should be standardised
      when both groups are included in multivariate studies.

PMID- 9018726
TI  - Neonatal respiratory distress syndrome in Karachi: some epidemiological
      considerations.
AB  - Although respiratory distress syndrome (RDS) is a leading cause of neonatal
      morbidity and mortality in the west, there are few data on the prevalence and
      spectrum of RDS from developing countries. Available evidence suggests that the
      disorder may be less common than the overall 1% incidence reported from developed
      countries. In a prospective study of the prevalence of RDS in a consecutive
      10,134 births at the Aga Khan University Hospital, we documented the disorder in
      127 (1.2% births), with a prevalence of 12.8% among low birthweight infants. The
      overall mortality for this group was 39%, with the highest mortality rate (68%)
      among newborn infants < or = 1000 g birthweight. Our data from a large and
      relatively well-nourished hospital-born population in Karachi suggest that RDS is
      a significant cause of morbidity and mortality in preterm infants with a similar
      prevalence rate to western figures.

PMID- 9018727
TI  - Clinical approach to the analysis of causes of death in the first two years of
      life of very-low-birthweight infants in a multicentre setting.
AB  - Mortality in the first 2 years of 634 very-low-birthweight infants admitted to
      eight neonatal intensive care units in Italy, and the factors associated with the
      net probability of death from each cause, were studied by means of the Cox
      proportional hazard model. A clinical classification of the causes of death was
      used. Overall mortality was 33.7% (intercentre range 12.6-52.9%). The highest
      cause-specific mortality rates were observed for respiratory problems, intra
      ventricular haemorrhage (IVH) and infections (14.5%, 6.3% and 5.7% respectively).
      The leading causes of death were respiratory problems and IVH in the first week
      of life, infections from the second week up to the end of the first month, and
      bronchopulmonary dysplasia (BPD) afterwards. Birthweight < 1000 g, gestational
      age < 30 weeks, absence of spontaneous respiratory activity, unknown body
      temperature and pH < 7.20 at admission were associated with death from
      respiratory problems and IVH. Male sex, birthweight < 1000 g and unknown body
      temperature at admission were associated with death from BPD. Mortality from
      infections was higher in one centre; no other differences emerged among the eight
      NICUs. The classification of the causes of death employed and the use of the net
      probabilities of death appear as practical and useful instruments to study the
      relationship between specific aspects of medical care and mortality, and to
      investigate the reasons for differences in performance between neonatal units.

PMID- 9018728
TI  - Month of birth as an independent variable in the sudden infant death syndrome.
AB  - Well-known epidemiological features of sudden infant death syndrome (SIDS) are
      age at death and the increased numbers in winter. There are more SIDS deaths in
      late autumn/early winter and there is a seasonal rhythm of births with a peak in
      late summer and early autumn. The data set was 14033 SIDS deaths from Scotland,
      England and Wales over the 11 years 1982-92. Using log-linear models, which
      accounted for age at death and month of death, birth month was found to be a
      statistically significant risk factor for SIDS independent of age at death and
      winter environment (P < 0.001). Although winter season had the largest effect
      (relative risk 2.7 in January compared with August), the independent effect of
      birth month was of clinical as well as statistical significance with a relative
      risk for August births of 1.37 compared with those born in April. The analysis of
      each birth month cohort revealed a change in age distribution with infants born
      in early winter (December) dying at a younger age (mean 108 days) than those born
      in midsummer (June) (mean 146 days). Although winter season and age are the most
      influential factors, the substantial effect of month of birth requires
      explanation and points to as yet unidentified environmental influences during
      pregnancy.

PMID- 9018729
TI  - Sudden infant death syndrome and parental smoking--a literature review.
AB  - There are a variety of methodological problems with published studies of parental
      smoking and sudden infant death syndrome (SIDS), with over-control the most
      consistent and problematic. Nevertheless, even though this is likely to minimise
      the true magnitude of relationships, the results are consistent. There are five
      cohort studies with prospectively collected information on maternal smoking in
      pregnancy: all show strong and statistically significant relationships that were
      dose dependent-the more cigarettes the mother had smoked, the more at risk was
      the baby of SIDS. Similar results have been shown from the case-control studies
      in which information has been collected retrospectively from parents or birth
      certificates. There are data from several studies indicating that environmental
      tobacco smoke (ETS) is also important. Since it has not yet been possible to
      determine conclusively whether associations are with smoking (or ETS) during
      pregnancy or postnatally, it is concluded that both should be discouraged.

PMID- 9018730
TI  - Evaluation of reproductive histories constructed by linking vital records.
AB  - We used 1.4 million fetal death and birth certificates filed in Georgia between
      1980 and 1992 to construct 369,686 chains of two or more reproductive events
      occurring to the same woman. We evaluated these chains using both information on
      the certificates and information independently collected in interviews with 1311
      women. Overall, 86.6% of the chains had the expected number of events, based on
      the certificate's information about previous pregnancies. Seventy-nine per cent
      of the chains had the expected number of events based on the maternal interviews.
      Consistency between the observed number of events in the chain and the number
      expected, based either on data from the certificates or from the maternal
      interviews, was greatest for chains with two or three events. Mothers born in
      Georgia were more likely to have complete chains than mothers born elsewhere.
      Among the 551,391 non-linked certificates, 48.7% were the mother's first birth,
      40.2% were second or higher-order births to women whose previous pregnancy
      occurred before 1980, and 11.1% were second or higher-order births to women whose
      previous pregnancy occurred after 1980. Fetal death and livebirth certificates
      can be linked to construct pregnancy histories with reasonably low levels of
      underlinkage and overlinkage.

PMID- 9018731
TI  - Identification of neonatal deaths in a large managed care organisation.
AB  - The neonatal (< 28 days) mortality rate (NMR) is one of the most commonly
      employed maternal and child health epidemiological measures. It is also being
      employed in quality measures ("report cards') used to assess the performance of
      health care organisations. The objectives were to (1) develop methods for the
      rapid quantification of the neonatal mortality rate in a multi-hospital system,
      the Kaiser Permanente Medical Care Program's Northern California Region (KPMCP
      NCR), (2) develop methods for generating facility-specific rates and case lists,
      and (3) ascertain the capture rates of the information sources available to us.
      Potential neonatal deaths were identified in the KPMCP NCR for the 1990 and 1991
      calendar years from 3 sources: (1) clerical searches of local facility records,
      (2) electronic searches of the KPMCP NCR hospitalisation database, and (3)
      linking KPMCP electronic birth records to death certificate tapes. The medical
      records of all infants identified through these methods were reviewed. The
      neonatal mortality rate was calculated in three ways: (1) including all
      livebirths, (2) excluding births weighing < 500 g, and (3) adjusting for
      prematurity by increasing the follow-up period in preterm babies (these babies
      were included as neonatal deaths if they died up to 40 weeks corrected age + 27.9
      days). A total of 352 records out of 64 469 birth records in the KPMCP NCR were
      reviewed. If one includes babies < 500 g, the neonatal mortality rate was
      3.72/1000 livebirths; if these babies are excluded, the rate was 3.05/1000.
      Adjusting for prematurity increased these rates to 3.91/1000 and 3.24/1000,
      respectively. Accurate quantification of the neonatal mortality rate in a multi
      hospital system requires the use of multiple information sources. Use of a single
      source can lead to varying rates of over- or under-estimation. It is possible to
      employ our methodology for both research and operational purposes.

PMID- 9018732
TI  - Evaluation of prenatal care information on birth certificates.
AB  - Misclassification frequently leads to bias in epidemiological studies, and causes
      concern for perinatal epidemiologists interested in using birth certificates as a
      data source. We used a maximum likelihood method to estimate the classification
      probabilities (conditional probabilities that indicate the probability of
      classification in a particular category, given the person's true category) of two
      data sources for a three-category outcome of prenatal care. The probability that
      women receiving adequate or inadequate care were correctly classified was
      estimated to be greater than 90%. The probability was much lower (< 35%) that
      women receiving intermediate care were correctly classified. The
      misclassification women from the intermediate category resulted in poor
      predictive values (< 70%) of women classified as receiving either adequate or
      inadequate care. Because of these findings, we combined the adequate and
      intermediate categories to form a two-category classification system. This
      revision resulted in higher positive predictive values (> 90%) with only a
      slightly lower classification probability (> 85%) for the combined category. We
      conclude that the degree of accuracy for a two-category classification of
      prenatal care based upon birth certificate information is acceptable, but we
      question the accuracy of indices of prenatal care with more than two categories.

PMID- 9018733
TI  - The quality of vital perinatal statistics data, with special reference to
      prenatal care.

PMID- 9018759
TI  - Gastrin stimulates histamine release from the isolated pig stomach.
AB  - BACKGROUND: Gastrin has been shown to give an immediate and dose-dependent
      histamine release preceding acid secretion in the totally isolated, vascularly
      perfused rat stomach. METHODS: In the present study we prepared isolated,
      vascularly perfused stomachs taken from pigs and examined the effect of
      pentagastrin in a concentration of 520 pM on the histamine release to the
      vascular bed. Pentagastrin was given for three 5-min periods at 10-min intervals,
      and histamine was determined by a radioimmunoassay method. RESULTS: Each
      pentagastrin dose resulted in stimulation of histamine release in the three pig
      stomachs examined. The various histamine concentrations increased to levels
      previously shown to stimulate aminopyrine accumulation in isolated pig parietal
      cells. CONCLUSION: The present study shows for the first time that gastrin
      induces histamine release to the vascular bed in the pig, as previously shown for
      the rat and dog.

PMID- 9018760
TI  - Expression of epidermal growth factor and transforming growth factor alpha during
      ulcer healing. Time sequence study.
AB  - BACKGROUND: Growth factors such as epidermal growth factor (EGF) and transforming
      growth factor alpha (TGF alpha) have been shown to share common receptor (EGFR)
      and to accelerate ulcer healing due to stimulation of cell proliferation, but the
      time sequence of expression of EGF and TGF alpha during ulcer healing has not
      been investigated. In this study the rate of cell proliferation and the gastric
      secretion and gene expression of mRNA for EGF and TGF alpha were determined
      during ulcer healing. METHODS: Gastric ulcers were induced in 150 Wistar rats by
      serosal application of 100% acetic acid (ulcer area, 14 mm2). Some of these
      animals were also equipped with a gastric fistula for the assessment of gastric
      secretion during ulcer healing. The animals were killed 0, 2, 4, 6, or 8 days
      after ulcer induction, and the ulcer area was determined. The mucosal sections
      with gastric ulcer were immunostained for proliferating cell nuclear antigen
      (PCNA) and for immunoexpression of EGF, TGF alpha, and EGFR. The expression of
      mRNA EGF and mRNA TGF alpha was also determined in the ulcer margin by reverse
      transcriptase (RT) polymerase chain reaction (PCR) using specific primers.
      RESULTS: Two, 4, 6, and 8 days after ulcer induction the gastric ulcer area was
      gradually reduced from the initial size (day 0) by 47%, 70%, 80%, and 87%,
      respectively, and this was accompanied by an increase in PCNA with its maximum on
      day 4. The gastric acid and pepsin secretion was significantly reduced by 75% and
      79%, respectively, on day 2 after ulcer induction but then the secretion tended
      to return to normal value by day 8. The expression of EGF, TGF alpha, and EGFR
      was negligible on day 0 but increased significantly during the healing, reaching
      maximum on day 4. Expression of EGF mRNA was detected on days 2, 4, and 6, and
      that of TGF alpha mRNA on days 2, 4, 6, and 8 after ulcer induction, with the
      most intense signals for both transcripts observed on day 2. CONCLUSIONS: 1) The
      enhancement in cell proliferation during ulcer healing may be mediated by
      increased release of EGF and TGF alpha; 2) the expression of EGF and TGF alpha
      mRNA precedes the overexpression of these growth factors at the ulcer margin
      during ulcer healing; and 3) the overexpression of growth factors coincides with
      the inhibition of gastric secretion and increased blood flow at the ulcer margin,
      indicating that these factors affect gastric secretion and blood flow in the
      course of ulcer healing.

PMID- 9018761
TI  - Genetic markers for peptic ulcer. A study of 3387 men aged 54 to 74 years: the
      Copenhagen Male Study.
AB  - BACKGROUND: Knowledge on the genetic risk of peptic ulcer has predominantly been
      based on hospital materials. To minimize selection bias, we tested the
      association between some genetic markers and the risk of peptic ulcer in a large
      scale epidemiologic design. METHODS: Some 3387 white men aged 55-74 years were
      investigated and reported their history of peptic ulcer. Information about
      hospitalization and operation was collected from registers. RESULTS: The lifetime
      prevalence of peptic ulcer in men with the Lewis phenotype Le(a + b-) and non
      secretors of ABH antigen was 15%, significantly higher than others, 11% (P <
      0.01); the risk in phenotypes O and A were equally high, 12%, and among other ABO
      groups, 7% (P < 0.05). Men with phenotype O had significantly higher risk of
      hospitalization than others (P < 0.01). Compared with others, the attributable
      risk of peptic ulcer in men who were Le(a + b-) or non-secretors, with O or A
      phenotypes, was 37%. No association was found with complement C3, MNS, or Rhesus
      blood groups. CONCLUSIONS: 1) The Le(a + b-) phenotype and the ABH non-secretor
      trait are relevant genetic markers of peptic ulcer. We suggest that these men
      have increased susceptibility to Helicobacter pylori infection. 2) This study
      challenges the importance of the ABO blood group: lifetime prevalence was equally
      high among men with O and A phenotypes, with more severe cases in men with
      phenotype O.

PMID- 9018762
TI  - Expression of mRNA for interferon-gamma, interleukin-10, and interleukin-12 (p40)
      in normal gastric mucosa and in mucosa infected with Helicobacter pylori.
AB  - BACKGROUND: We studied the mRNA expressions of interferon-gamma (IFN-gamma),
      interleukin-10 (IL-10), and IL-12 in gastric biopsy and blood samples from
      patients with and without Helicobacter pylori infection, by reverse-transcription
      polymerase chain reaction (RT-PCR). METHODS: RT-PCR was performed on total RNA
      preparations, and the expressed mRNA were semiquantitated on the basis of band
      intensities on Southern blots. RESULTS: In gastric mucosa the expression of IFN
      gamma and IL-10 was found in most patients with and without H. pylori infection,
      whereas IL-12 was found in most of the infected ones. The level of IFN-gamma and
      IL-10 did not differ between groups, whereas the IL-12 level was significantly
      higher in those with H. pylori infection. In the blood IFN-gamma expression was
      found in most samples, with higher level in patients with gastritis than in
      normals. Few blood samples (33%) had IL-12, and none had IL-10. CONCLUSION: IFN
      gamma and IL-10 expressions in healthy mucosa may indicate a biologic role in a
      healthy state. IL-12 expression in mucosa was related to the presence of
      bacterial stimulant and therefore resembles proinflammatory cytokines.

PMID- 9018763
TI  - A comparison of Helicobacter pylori and H. heilmannii gastritis. A matched
      control study involving 404 patients.
AB  - BACKGROUND: Since Helicobacter heilmannii gastritis is very much rarer than H.
      pylori gastritis, and no systematic studies comparing these two gastritides have
      so far been carried out, we undertook the present study to investigate possible
      differences between H. heilmannii and H. pylori gastritis. METHODS: In 202
      patients with H. heilmannii gastritis and 202 matched control patients with H.
      pylori gastritis and duodenal ulcer the following variables were graded and
      compared: Helicobacter colonization, chronicity of gastritis, activity of
      gastritis, replacement of foveolar epithelium by regenerative epithelium, mucus
      depletion, frequency of acquired mucosa-associated lymphoid tissue (MALT), and
      intestinal metaplasia. RESULTS: In contrast to the diffuse pattern of
      colonization in the case of H. pylori, colonization with H. heilmannii is mainly
      (91.2%) focal and for the most part restricted to the antrum (only 29.1%
      concurrent colonization of the corpus). The gradings of all gastritis variables
      were statistically highly significantly milder in the case of H. heilmannii
      gastritis. In addition, intestinal metaplasia and acquired MALT were
      significantly less common in patients with H. heilmannii infection. The rare
      cases of erosions (n = 8) and ulcerations (n = 8) in H. heilmannii gastritis were
      usually associated with the use of non-steroidal anti-inflammatory drugs. In a
      single case of H. heilmannii gastritis a concurrent gastric carcinoma and in
      seven cases a low-grade gastric MALT lymphoma were found. CONCLUSION: In contrast
      to H. pylori infection the rare colonization of the gastric mucosa with H.
      heilmannii, mainly circumscribed and mostly in the antrum, induces a very much
      milder form of gastritis in the antrum and corpus, which may also be the reason
      for the rarity of concurrent erosions and ulcers. Whether the observed relatively
      frequent association of H. heilmannii infection and gastric MALT lymphoma is
      coincidental, and whether H. heilmannii gastritis is more commonly associated
      with MALT lymphoma than is H. pylori gastritis must be investigated in further
      studies.

PMID- 9018764
TI  - Effects of loperamide oxide on gastrointestinal transit time and anorectal
      function in patients with chronic diarrhoea and faecal incontinence.
AB  - BACKGROUND: Loperamide improves anorectal function in patients with chronic
      diarrhoea. We wished to investigate whether the prodrug loperamide oxide has
      similar effects. METHODS: Eleven patients with chronic diarrhoea and faecal
      incontinence participated in a randomized, placebo-controlled, double-blind,
      crossover study of the effects of loperamide oxide (4 mg twice daily for 1 week).
      RESULTS: Loperamide oxide reduced wet stool weight and improved the patients'
      ratings of symptoms. Mouth-to-caecum transit time was not altered, but whole-gut
      transit time was prolonged. There were limited effects on anorectal function, but
      the mean minimum basal pressure mainly contributed by the internal anal sphincter
      (IAS) was increased, as was the mean volume infused before leakage occurred in
      the saline continence test. CONCLUSION: Loperamide oxide is effective in the
      treatment of diarrhoea with faecal incontinence; normalization of colon transit
      time and an increase in the tone of the IAS seem to be the main determinants of
      efficacy.

PMID- 9018765
TI  - Large-scale ambulatory study of postprandial jejunal motility in irritable bowel
      syndrome.
AB  - BACKGROUND: The relationship of small-bowel dysmotility to dietary intake in
      irritable bowel syndrome (IBS) is obscure. METHODS: This study evaluated
      postprandial jejunal motility in IBS patients classified as constipation
      predominant (n = 25) or diarrhoea-predominant (n = 35) and compared results
      against 18 volunteers. Twenty-four-hour ambulatory jejunal manometry was carried
      out in all subjects, and recordings were analysed by microcomputer and visual
      assessment. RESULTS: By means of analysis of variance (fitting factors for
      channels, meals, and time periods) postprandial contraction frequency was greater
      in both patient groups compared with normal (constipation-predominant versus
      normal, diarrhoea-predominant versus normal; P < 0.001). In the constipation
      predominant cohort, contraction amplitudes were lower (constipation-predominant
      versus normal; P < 0.002). Discrete cluster contractions occurred with similar
      frequency and duration in both patient and volunteer groups. CONCLUSIONS:
      Quantitative differences of postprandial jejunal contraction characteristics have
      been shown between patients with IBS and healthy volunteers. Contraction
      frequency is greater than normal in both diarrhoea- and constipation-predominant
      categories, whereas contraction amplitudes are lower in constipation-predominant
      patients.

PMID- 9018766
TI  - Giardiasis: a histologic analysis of 567 cases.
AB  - BACKGROUND: The histopathology of the upper and lower gastrointestinal tract of
      patients with giardiasis as shown by endoscopy with biopsy is ill-defined. We
      therefore report on 567 cases observed in our institution. METHODS: A
      retrospective analysis of all cases with giardiasis observed between 1988 and
      1994 was performed. RESULTS: On histologic slides trophozoites were found in
      duodenal (82.5%) and jejunal (2.1%) mucosa and also in gastric antral (8.7%) and
      ileal mucosa (12.1%) but rarely in the colon (0.4%). An entirely normal light
      microscopic appearance of the duodenal mucosa was found in 462 cases (96.3%).
      Mild villous shortening and mild inflammation of the lamina propria were observed
      in duodenal mucosa in 18 subjects (3.7%). In jejunal, ileal, gastric, and colonic
      mucosa, no Giardia-specific histologic changes were identified. There was a clear
      male predominance with 347 (61.2%) males and 220 (38.8%) females. Mean age, which
      was comparable in males and females, was 49.5 +/- 17 years (range, 3-95 years).
      In 252 Giardia-positive cases gastric biopsy specimens were available, and showed
      Helicobacter pylori-associated gastritis in 57.8%, reactive gastritis in 10.3%,
      normal mucosa in 12.9%, chronic atrophic gastritis of the body in 2.9%, and other
      forms of gastritis in 16.1%. CONCLUSIONS: This study shows that the histology of
      the small-bowel mucosa is inconspicuous in most subjects with giardiasis. A
      search for the parasite must therefore be made in all biopsy samples obtained
      from this area. Furthermore, giardiasis was not associated with a particular
      gastric disease, such as chronic atrophic gastritis of the body.

PMID- 9018767
TI  - Epidemiology of Whipple's disease in Germany. Analysis of 110 patients diagnosed
      in 1965-95.
AB  - BACKGROUND: The epidemiology of Whipple's disease (WD) is obscure. To obtain
      basic data, we performed an evaluation of WD patients in Germany. METHODS:
      Information was collected from 110 WD patients diagnosed during 1965-95 at 5
      institutions in different regions of Germany. Four items were evaluated: 1) year
      in which the diagnosis was made; 2) residence and 3) age at the time of
      diagnosis; and 4) sex. RESULTS: WD patients originated from all parts of Germany.
      The incidence of new cases was relatively stable, with a mean of one to two cases
      per year per collecting centre. In 1995, a maximum of 13 new WD patients was
      diagnosed. There was a significant increase in the mean age of patients (1965-75,
      48.7 years; confidence interval, +/- 3.98 years; 1976-85, 50.7 years, +/- 3.69
      years; 1986-95, 57.0 years, +/- 2.80 years; P < 0.01) and an increasing
      proportion of women (1965-85, 4%; 1986-1995, 22%). CONCLUSIONS: Whipple's disease
      is not quite as rare as commonly assumed. There is no obvious geographic
      predominance. During the past three decades, the demography of WD patients has
      changed.

PMID- 9018768
TI  - Role of transanal endoscopic microsurgery in the palliative treatment of rectal
      cancer.
AB  - BACKGROUND: Palliative, minimal invasive treatment of rectal cancer is advocated
      in patients with advanced and incurable disease or poor clinical condition and in
      those who refuse radical surgery. Several methods have been used during recent
      years. We report our experience with palliative transanal endoscopic
      microsurgery. MATERIALS: Between 1983 and 1995, 29 patients underwent transanal
      endoscopic microsurgery for palliation. Eleven patients had advanced malignant
      disease, nine were in poor clinical condition, and nine repeatedly refused
      radical surgery. RESULTS: Intraoperatively one severe complication, an intra
      abdominal perforation, occurred. The morbidity rate was 14%. Postoperatively,
      clinical signs were abolished or improved in all cases. Only three patients
      required further palliative resections after initial symptom relief. CONCLUSIONS:
      Transanal endoscopic microsurgery is a successful approach in the palliative
      treatment of rectal cancer. The technique enables complete resection of rectal
      tumors. Although anesthesia is needed, the morbidity is low, even in patients
      with poor clinical condition.

PMID- 9018769
TI  - K-ras mutations and prognosis in large-bowel carcinomas.
AB  - BACKGROUND: Colorectal carcinogenesis is regarded as a multistep process
      involving several genetic alterations, with mutation in the K-ras gene in about
      half of the tumours. We aimed at clarifying the role of this genetic alteration
      related to survival and clinicopathologic variables. METHODS: One hundred large
      bowel carcinomas operated on between 1978 and 1982 were studied for the presence
      of point mutations in codons 12 and 13 of the K-ras gene, using enriched
      polymerase chain reaction amplification, restriction fragment length polymorphism
      analysis, and direct sequencing. RESULTS: Forty mutations were found (40%): 31 in
      codon 12 and 9 in codon 13, 7 different types. There was no relationship between
      tumours with and without K-ras mutations with regard to Dukes' stages, age or sex
      of the patient, tumour localization, histologic grade, DNA ploidy pattern, HLA-DR
      staining pattern, or survival. Samples from 5 different localizations in 7
      carcinomas showed identical K-ras mutation pattern, as did 19 recurrences/
      metastases originating from 11 carcinomas. CONCLUSIONS: When present, the primary
      tumour shows homogeneous distribution of K-ras mutation, and the mutation follows
      the carcinoma in the secondary deposit, regardless of lymphogenous or
      hematogenous spread. The presence of K-ras mutation does not seem to have
      prognostic significance for the patient, and the precise nucleotide change is
      furthermore not predictive of tumour behaviour.

PMID- 9018770
TI  - Influence of viral genotype and level of viremia on the severity of liver injury
      and the response to interferon therapy in Spanish patients with chronic C
      infection.
AB  - BACKGROUND: We wanted to investigate the influence of viral genotype on the
      severity of liver injury and response to interferon and whether the level of
      viremia differs in accordance with genotype, severity of liver disease, and
      response to interferon in patients with hepatitis C virus (HCV) infection.
      METHODS: We studied 118 patients with HCV-related liver disease. HCV genotypes
      were determined with a line probe assay, and serum HCV RNA levels with a
      competitive reverse transcription polymerase chain reaction assay. RESULTS: HCV
      type 1b was the most prevalent genotype (88%). It was present in 100% of
      cirrhotic patients, with or without hepatocellular carcinoma (HCC), but only in
      78% of patients with chronic hepatitis (P < 0.001). The response to interferon
      was better in patients infected with non-1b HCV genotypes (P = 0.002). In a
      multivariate analysis non-1b HCV genotypes and a low hepatic fibrosis correlated
      with a favorable response to interferon. Among patients with chronic hepatitis
      those infected with HCV type 1b were older (P < 0.001), and age was the only
      independent factor associated with HCV type 1b. Viremia levels differed neither
      between genotypes nor in response to interferon and was significantly lower in
      patients with cirrhosis and HCC. CONCLUSIONS: HCV 1b was associated with more
      severe liver disease and a worse response to interferon therapy. Non-1b genotypes
      and a lower liver fibrosis were the only independent predictors of a favorable
      response to interferon. Levels of HCV viremia differed neither among different
      genotypes nor in response to interferon and decreased with advanced liver
      disease.

PMID- 9018771
TI  - Primary biliary cirrhosis in The Netherlands. An analysis of associated diseases,
      cardiovascular risk, and malignancies on the basis of mortality figures.
AB  - BACKGROUND/METHODS: In 1979 death rate registration for primary biliary cirrhosis
      (PBC) became available in The Netherlands. In the 14-year period 1979-92, 417
      persons died of and 179 with PBC. We investigated secondary causes of death using
      standardized mortality ratios (SMR) (1.0 as reference, P < 0.001 regarded as
      significant). RESULTS: Median age was 70-74 (35 to > 85) years. Secondary causes
      of death originated from the circulatory, digestive, and respiratory tracts and
      malignancies. Younger persons (< 60 years), dying of PBC, more often died with
      "toxicity related to immunosuppression' than older persons (P < 0.01). Younger
      persons (< 60) dying with PBC, more often died of hepatocellular carcinoma (HCC)
      than older ones (P < 0.05). In patients with PBC the frequency of HCC (SMR, 25.5;
      P < 0.0001) and diseases of the musculoskeletal system/connective tissue (SMR,
      5.1; P < 0.0001) was higher than in the general population. Malignancies in
      general (SMR, 0.7), pancreatic carcinoma (SMR, 2.5), breast cancer (SMR, 0.1) and
      diseases of the circulatory system (SMR, 0.8) differed but not significantly (P <
      0.05 - < 0.01). No difference existed in the localization of malignancies in
      patients dying of as compared with those dying with PBC. CONCLUSIONS: Deaths
      occurred predominantly in the older age classes, with an age-related difference
      in some associated disorders. Patients with PBC showed an increased risk of HCC
      and diseases of the musculoskeletal system. Similar studies from different
      countries are needed.

PMID- 9018772
TI  - Peptide leukotriene receptor antagonist diminishes pancreatic edema formation in
      rats with cerulein-induced acute pancreatitis.
AB  - BACKGROUND: This study was designed to evaluate the protective effect of a
      peptide leukotriene receptor antagonist, pranlukast hydrate, against pancreatic
      injuries during acute pancreatitis. METHODS: Acute pancreatitis was induced in
      rats by intravenous infusion of a supramaximal dose of cerulein (5 micrograms/kg
      h for 4 h). In this model marked hyperamylasemia, a significant increase in
      pancreatic water content, and a significant increase in pancreatic microvascular
      leakage of Evans blue dye were observed. Pancreatic subcellular redistribution of
      the lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen
      fraction was also observed. RESULTS: Pretreatment with pranlukast hydrate at a
      dose of 10 micrograms/kg (twice, 8 and 4 h before cerulein infusion)
      significantly inhibited these pancreatic injuries, including hyperamylasemia,
      increased pancreatic microvascular permeability, and redistribution of cathepsin
      B in pancreatic acinar cells. CONCLUSIONS: These results suggest that peptide
      leukotrienes may be involved in the pathogenesis of acute pancreatitis in the
      early stage of the disease and that peptide leukotriene receptor antagonist might
      be of therapeutic value for treatment of acute pancreatitis.

PMID- 9018773
TI  - Recurrence of acute colonic pseudo-obstruction in selective adrenergic
      dysautonomia associated with infectious toxoplasmosis.
AB  - BACKGROUND: Acute colonic pseudo-obstruction is a life-threatening condition
      associated with several pathologic conditions, whose pathophysiology is still
      uncertain. CASE: Autonomic function in a young patient operated on for acute
      colonic pseudo-obstruction was carefully evaluated; none of the common clinical
      conditions described in the literature was found to have caused the syndrome.
      Selective adrenergic failure was suggested by the presence of severe orthostatic
      hypotension, low basal plasma catecholamine level, and absence of the expected
      increase on standing and by the findings of provocation tests, cardiovascular
      tests, and acetylcholine sweat spot test. Biopsy specimens from the colon and
      small-bowel wall did not show any morphologic or immunohistochemical alteration
      either in muscle layers or in the autonomic plexus, testifying to the possible
      occurrence of extrinsic denervation in the presence of an intact plexus.
      Infectious toxoplasmosis was proved through indirect and direct hemagglutination
      assays, enzyme-linked immunosorbent assay IgG, IgM, and IgA, immunosorbent
      agglutination IgM assay, and the protozoa were demonstrated in a biopsy specimen
      from the rectus abdominis muscle. CONCLUSIONS: Selective adrenergic denervation
      of the gut resulted in recurrent episodes of colonic pseudo-obstruction, probably
      by direct toxicity or a cross-reaction between the immune process and a
      toxoplasmic antigen, stressing the importance of sympathetic inhibitory
      modulation on colon motor activity.

PMID- 9018774
TI  - Therapeutic potential of NSAIDs and omeprazole in the oesophagus.

PMID- 9018775
TI  - Endoscopic sphincterotomy and gallbladder functions.

PMID- 9018776
TI  - Molecular epidemiology, in 1994, of Neisseria gonorrhoeae in Manila and Cebu
      City, Republic of the Philippines.
AB  - BACKGROUND AND OBJECTIVES: Failure of gonococcal infections to respond to 500 mg
      of ciprofloxacin or 400 mg of ofloxacin has been reported from Australia, the
      United Kingdom, and the United States. Recently, high rates of decreased
      susceptibility to the fluoroquinolones have been detected in penicillinase
      producing Neisseria gonorrhoeae in the Republic of the Philippines. GOALS: To
      assess the diversity of antimicrobial-resistant gonococcal strains isolated from
      female sex workers in Manila and Cebu City in the Republic of the Philippines in
      1994. STUDY DESIGN: Isolates of N. gonorrhoeae isolated from 92 female sex
      workers in Manila (n = 28) and Cebu City (n = 64), respectively, were
      characterized by plasmid profile, auxotype/serovar class, and antimicrobial
      susceptibility profile. RESULTS: Plasmid-mediated resistance to penicillin or
      tetracycline was identified in 79.3% (73/92) of the isolates: penicillinase
      producing N. gonorrhoeae (65/92; 70.7%), tetracycline-resistant N. gonorrhoeae
      (6/92; 6.5%), and penicillinase-producing/tetracycline-resistant N. gonorrhoeae
      (1/92; 1.1%). A beta-lactamase plasmid of 3.9 megadaltons was discovered. Of
      54.3% (50/92) of strains resistant to nalidixic acid, 84% (42/50) of strains had
      minimum inhibitory concentrations of > or = 0.125 microgram/ml ciprofloxacin;
      penicillinase-producing N. gonorrhoeae (possessing the 3.05-, 3.2-, 3.9-, and 4.4
      megadalton beta-lactamase plasmids, respectively) accounted for 68% (34/50) of
      these strains. CONCLUSIONS: In the Republic of the Philippines, gonococcal
      isolates resistant to penicillin or tetracycline accounted for 85.9% (79/92) of
      the isolates examined and included strains exhibiting resistance to
      fluoroquinolones. All gonococcal infections should be treated with antimicrobial
      therapies known to be active against all gonococcal strains to reduce the spread
      of strains exhibiting decreased susceptibilities to fluoroquinolones.

PMID- 9018777
TI  - Sexually transmitted diseases in patients attending a Baltimore tuberculosis
      clinic. Assessment of use of multiple categoric services.
AB  - BACKGROUND: Recent increases in the incidence of tuberculosis and syphilis have
      occurred disproportionately in young heterosexuals of low socioeconomic status.
      The authors hypothesized that an overlap of tuberculosis and sexually transmitted
      disease clinic populations potentially could result in inefficient use of limited
      public health resources. METHODS: The authors conducted a retrospective study to
      determine the coinfection rate of syphilis and other sexually transmitted
      diseases in patients seen for evaluation at the Baltimore City Tuberculosis
      Clinic, Baltimore, Maryland. The authors determined the sexually transmitted
      disease clinic utilization patterns of this patient population. RESULTS: For
      patients referred to the tuberculosis clinic, 9.0% had a history of syphilis and
      13.6% had at least one documented visit at a Baltimore City sexually transmitted
      disease clinic. Blacks presenting to the tuberculosis clinic were more likely to
      have previously diagnosed syphilis (13.6%) and to have had visited the sexually
      transmitted disease clinics (16.5%). CONCLUSIONS: In Baltimore, the patient
      population of tuberculosis clinics overlaps with those at the public sexually
      transmitted disease clinics. Thus, cross screening for syphilis and tuberculosis
      at urban clinics would be an important mechanism for identifying new cases of
      disease and increasing the efficiency of the public health system.

PMID- 9018778
TI  - Use and effectiveness of condoms during anal intercourse. A review.
AB  - BACKGROUND AND OBJECTIVES: Anal intercourse has been associated with a high risk
      of human immunodeficiency virus transmission. Survey data suggest that
      unprotected anal intercourse is practiced by a substantial proportion of the
      sexually active population, regardless of sexual orientation. GOAL: To review the
      literature related to the use and effectiveness of condoms during anal
      intercourse, with emphasis on prevention of human immunodeficiency virus
      transmission. STUDY DESIGN: Literature review. RESULTS: Epidemiologic studies
      have shown that consistent, correct condom use reduces the overall risk of sexual
      transmission of human immunodeficiency virus. Evidence for the effectiveness of
      condoms used during anal intercourse is less definitive. Survey and clinical
      trials data indicate that condom breakage and slippage rates vary during anal
      intercourse and may be considerably higher than during vaginal intercourse.
      Although condoms designed for anal intercourse have been studied and marketed in
      Europe, data on their actual performance are scarce. In addition, no information
      exists on the effectiveness of polyurethane or other nonlatex condoms for use
      during anal intercourse. CONCLUSIONS: Development of newer and more effective
      condoms for use during anal intercourse requires consideration of the ethical
      issues involved in testing and marketing devices used during an activity that
      carries with it the potential for a substantial risk to health.

PMID- 9018780
TI  - Risk factors for oral human papillomavirus in adults infected and not infected
      with human immunodeficiency virus.
AB  - BACKGROUND AND OBJECTIVES: To investigate in a cross-sectional study the
      determinants of oral human papillomavirus infection in 287 individuals who are
      sexually active. GOAL: To assess prevalence as well as risk factors for oral
      human papillomavirus infection. STUDY DESIGN: One hundred seventy-eight human
      immunodeficiency virus-seropositive (158 men and 20 women) and 109 human
      immunodeficiency virus-negative (73 men and 36 women) individuals were recruited
      consecutively from sexually transmitted disease-human immunodeficiency virus
      clinics and gastrointestinal endoscopy clinics. Oral brushings were tested with
      the L1 consensus polymerase chain reaction assay for human papillomavirus
      detection. RESULTS: Human papillomavirus DNA was detected in 32 (11.2%) of 287
      individuals. Associated with oral human papillomavirus infection on univariate
      analyses were human immunodeficiency virus infection (odds ratio, 6.9; 95%
      confidence interval, 2.0-23.2), homosexuality (odds ratio, 3.7; 95% confidence
      interval, 1.5-9.4), unprotected oral sex (odds ratio, 5.5; 95% confidence
      interval, 1.6-18.4), syphilis (odds ratio, 2.5; 95% confidence interval, 1.1
      6.3), gonorrhea (odds ratio, 4.2; 95% confidence interval, 1.9-9.1), Chlamydia
      trachomatis (odds ratio, 4.4; 95% confidence interval, 1.8-10.6), and genital
      herpes (odds ratio, 2.9; 95% confidence interval, 1.3-6.5). Human
      immunodeficiency virus infection and C. trachomatis were independently predictive
      of human papillomavirus infection in multivariate stepwise logistic regression.

PMID- 9018779
TI  - Antibiotic susceptibility patterns and plasmid profiles of penicillinase
      producing Neisseria gonorrhoeae strains in Durban, South Africa, 1990-1993.
AB  - BACKGROUND AND OBJECTIVES: The appearance of strains of Neisseria gonorrhoeae
      resistant, both chromosomally and plasmid-mediated, to penicillin and other
      antibiotics makes this versatile pathogen difficult to treat. There is,
      therefore, a need for surveillance of N. gonorrhoeae strains to determine the
      efficacy of current therapeutic measures. GOALS: To survey the antibiotic
      susceptibilities and plasmid profiles of penicillinase-producing N. gonorrhoeae
      strains isolated over a 4-year period. STUDY DESIGN: Penicillinase-producing N.
      gonorrhoeae strains were detected by the chromogenic cephalosporin test. Minimum
      inhibitory concentrations to penicillin G, tetracycline, ceftriaxone, and
      ciprofloxacin were determined using the E-test. Plasmid DNA was obtained by the
      alkaline lysis method and profiles generated. RESULTS: Penicillinase-producing N.
      gonorrhoeae strains increased from 16.4% to 19.0% in the period from 1990 through
      1993. Although all strains were resistant to penicillin, strains were susceptible
      to varying levels of ciprofloxacin, ceftriaxone, and even tetracycline. All
      penicillinase-producing N. gonorrhoeae strains possessed the 2.6-megadalton
      cryptic plasmid, and in addition 87.7% contained the 24.5-megadalton conjugative
      plasmid. Of the six known gonococcal beta-lactamase plasmids, the 4.4-megadalton
      Asian and 3.2-megadalton African plasmids were predominant. The most prevalent
      plasmid profile contained the 2.6-megadalton cryptic, 24.5-megadalton
      conjugative, and 4.4-megadalton Asian plasmids. CONCLUSIONS: To ensure effective
      treatment of gonorrhea, continued surveillance of the antimicrobial
      susceptibilities and plasmid profiles of penicillinase-producing N. gonorrhoeae
      strains is necessary.

PMID- 9018781
TI  - Increasing resistance of Neisseria gonorrhoeae in west and central Africa.
      Consequence on therapy of gonococcal infection.
AB  - BACKGROUND AND OBJECTIVES: Antimicrobial resistant strains of Neisseria
      gonorrhoeae have spread with remarkable rapidity in many African countries.
      Chromosomal resistance to penicillin, tetracycline, and thiamphenicol is frequent
      now, and reported prevalences of penicillinase-producing N. gonorrhoeae isolates
      vary between 15% and 80%. Plasmid-mediated tetracycline-resistant N. gonorrhoeae
      isolates have been observed in several African countries. GOALS: To characterize
      gonococcal isolates from three sites in West and Central Africa, to determine
      antimicrobial susceptibility patterns, to document the spread of plasmid-mediated
      resistance to penicillin and tetracycline in these three sites, and to discuss
      the consequences of rising antimicrobial resistance on the management of
      gonococcal infection in Africa. STUDY DESIGN: Over time, a total of 2,288
      gonococcal isolates were obtained from Abidjan, Ivory Coast (1992-1993, n = 251),
      from Kigali, Rwanda (1988-1993, n = 952), and from Kinshasa, Zaire (1988-1990, n
      = 1,085). The isolates were characterized by auxotyping and serotyping. Plasmid
      mediated resistance to penicillin and to tetracycline was determined.
      Antimicrobial susceptibility testing to ceftriaxone, ciprofloxacin, penicillin,
      spectinomycin, tetracycline, and thiamphenicol was performed with an agar
      dilution method. RESULTS: The prevalence of penicillinase-producing N.
      gonorrhoeae increased significantly over time from 44% to 57% in Kigali and
      remained stable at a high level in Abidjan (73%) and in Kinshasa (67%). The
      frequency of tetracycline-resistant N. gonorrhoeae increased significantly during
      the observation periods in all three sites: from 20% to 65% in Abidjan, from 0%
      to 64% in Kigali, and from 14% to 41% in Kinshasa. Chromosomal resistance to
      penicillin was common in Kigali and Kinshasa, and chromosomal resistance to
      tetracycline and thiamphenicol was frequent in all three sites. All gonococcal
      isolates were susceptible to ceftriaxone, ciprofloxacin, and spectinomycin.
      Prototrophic and proline requiring strains were predominant, and IA-6 was the
      most common serovar in the three sites. IB-specific serovars were more common
      among penicillinase-producing N. gonorrhoeae and IA-specific serovars were more
      frequent among tetracycline-resistant N. gonorrhoeae, but there was no evidence
      for a clonal spread of resistant strains. CONCLUSIONS: This study illustrates the
      high frequency of resistant gonococci in Africa and shows that tetracycline
      resistant N. gonorrhoeae have become highly endemic in different geographic areas
      of the continent. The use of effective drugs is essential to reduce gonorrhea
      transmission. Surveillance of temporal changes in antimicrobial resistance in
      gonococcal strain populations should be part of sexually transmitted diseases
      control programs.

PMID- 9018782
TI  - Interferon-gamma and interleukin-5 production by mice in response to genital
      infection by the mouse pneumonitis agent of Chlamydia trachomatis.
AB  - BACKGROUND AND OBJECTIVES: Mice sensitized with a chlamydial detergent extract
      and then genitally infected by Chlamydia trachomatis have increased genital
      inflammation characterized by elevated eosinophils, but do not have increased
      protective immunity. In contrast, mice infected previously by C. trachomatis show
      strong protective immunity. The authors studied interferon-gamma levels
      (associated with protective immunity) and interleukin-5 levels (the major
      cytokine responsible for eosinophilia). GOALS: To evaluate protective and
      nonprotective immune responses to chlamydial infection. STUDY DESIGN: The authors
      examined interferon-gamma and interleukin-5 levels in the genitalia during
      chlamydial genital infection among three groups of mice: extract-sensitized, sham
      sensitized, and infected previously. RESULTS: Interferon-gamma levels peaked
      between 24 and 72 hours after chlamydial infection and then declined among all
      groups of mice. Overall, interleukin-5 levels increased throughout infection.
      Interleukin-5 levels apparently continued to increase over the 5-week period
      after primary infection. CONCLUSIONS: Increased interferon-gamma levels were
      associated with an early response to chlamydial genital infection. Increased
      interleukin-5 levels were associated with a more persistent immune response.

PMID- 9018783
TI  - The role of sexual partnership networks in the epidemiology of gonorrhea.
AB  - BACKGROUND: Empirical studies have the potential to collect data on patterns of
      sexual mixing and network structures. GOAL: To explore the contribution of
      different network measures in sexually transmitted disease epidemiology. STUDY
      DESIGN: Individual-based stochastic simulations of a network of sexual
      partnerships and sexually transmitted disease transmission are analyzed using
      logistic regression. RESULTS AND CONCLUSIONS: Measures accumulated over times
      similar to the duration of infection are more informative than are static cross
      sections. The patterns of sexual mixing and network structure influence patterns
      of infection. In particular, the establishment of infection is most sensitive to
      the proportion of nonmonogamous pairs, the component distribution and cohesion
      among those with high activity. The subsequent prevalence is most sensitive to
      the assortativeness of mixing in the high-activity class and a measure of
      cohesion, both of which reflect the decrease in prevalence brought about by less
      widespread connections. A person's risk for infection is determined by local
      rather than global network structures.

PMID- 9018785
TI  - Rh serology--coordinator's report.
AB  - 168 Rh specific monoclonal antibodies (Mabs) were evaluated in 43 laboratories.
      Red cells from 63 Rh variant phenotype donations were circulated in panels to
      evaluators. Circulation was organised to ensure adequate duplicate testing.
      Evaluators were asked to test each Mab at 3 dilutions in two specified techniques
      against normal phenotype cells, panel cells received and any other Rh variant
      cells they had available. Results were analysed by expressing the sum of reaction
      grades for each Mab with each variant cell as a percentage of the sum of reaction
      grades of that Mab with normal phenotype cells. Reactions with enzyme-treated
      cells were found to be highly variable between laboratories, and further analysis
      of these results was not attempted. Anti-D Mabs were sorted into groups which had
      the same pattern of reactions with different phenotype cells. 24 such patterns
      were identified, 17 corresponding to previously reported patterns and 7 new ones.

PMID- 9018784
TI  - Azithromycin as a cost-effective treatment for nongonococcal urethritis in men.

PMID- 9018786
TI  - Monoclonal antibodies directed against human Rh antigens in tests with red cells
      of non-human primates.
AB  - Human anti-D (Rho) monoclonal antibodies (Mabs) of the IgG (70) and IgM (27)
      classes were tested with red blood cells (RBCs) of various non-human primates,
      from anthropoid apes to New World monkeys. Significant differences in reactivity
      were observed among antibodies of two classes depending on taxonomic position of
      primate animals. Only IgM Mabs gave positive reactions (9 out of 18 Mabs) with
      blood of Old World monkeys. Allotypic reactions with RBCs of African apes were
      produced by a majority of IgG Mabs but by very few IgM reagents, most of the
      latter reacting with RBCs of all chimpanzees and all gorillas tested. Eight out
      of 70 IgG anti-D defined chimpanzee polymorphisms related to chimpanzee Rc
      antigen which is the chimpanzee counterpart of human D antigen. Most of IgG anti
      D Mabs (61/70) were found specific of Dgor antigen (gorilla counterpart of human
      antigen D). Most of anti-D which were found negative with all chimpanzee RBCs
      were also negative with human DIVb RBCs and most of anti-D which agglutinated
      human DIVb RBCs were positive with some or all chimpanzee blood samples.
      Differences among Mabs evidenced in tests with non-human primate RBCs reflect the
      complexity of the immune reactions to the human D antigen. The results obtained
      with anti-Rh Mabs of specificities other than D confirmed that chimpanzee,
      gorilla and gibbon express c-like epitopes and that antigens C, E, e are absent
      in non-human primates.

PMID- 9018787
TI  - Polyreactivity of human monoclonal antibodies: human IgM anti-rhesus monoclonal
      antibodies are frequently polyreactive.
AB  - The aim of this study was to characterize human anti-Rhesus monoclonal antibodies
      cross-reacting with tissue antigens. Of the 155 monoclonal alloantibodies tested,
      49 also reacted with intracellular antigens, as demonstrated by
      immunofluorescence assay on cryostat sections of animal and human tissues. This
      cross-reactivity was mainly a property of monoclonal alloantibodies belonging to
      the IgM isotype (among the 49 cross-reacting Mabs, 37 were IgM). The results
      confirm that during an immune response against a foreign antigen (alloantigen), B
      cells that produce polyreactive antibodies are not excluded from the pool of
      responding cells.

PMID- 9018788
TI  - Specificity C and e: tests using Rh variant cells.
AB  - Monoclonal antibodies, specificity C, e, and Rh subgroup? ein the Section 1-Rh
      were tested with selected blood samples of various Rh variant types in KwaZulu
      Natal, South Africa. The standard red cell serological techniques supplied were
      used.

PMID- 9018789
TI  - Reactivity of 62 Rh MAbs with weak and variant antigens.
AB  - We characterized serologically 5 anti-C (4 IgM and 1 IgG), 3 anti-c (2 IgM and 1
      IgG), 4 anti-E (1 IgM and 3 IgG), 4 anti-e (3 IgM and 1 IgG) and 46 anti-D (16
      IgM and 30 IgG) monoclonal antibodies, provided by the Rh Section of the Third
      International Workshop and Symposium on Monoclonal Antibodies against Human Red
      Blood Cells and Related Antigens (1996) for their ability to detect weak and
      variant antigens. The agglutination patterns were established using untreated and
      papain-treated red blood cells in a column agglutination technology system
      (BioVue, Ortho). Significant differences were found between the IgM and IgG
      antibodies. The papain treatment seemed to be important for IgM but not for IgG
      antibodies. Almost all of the IgM anti-D antibodies detected untreated DIV
      samples and almost all of the IgG anti-D antibodies detected untreated weak D
      samples. Both IgM and IgG anti-D antibodies showed the highest number of negative
      reactions with DVI and Rh 33 red blood cells. The CwCw sample was detected by
      only one of the 4 anti-C IgM MAbs using enzyme-treated red blood cells. All anti
      c MAbs were able to detect treated Cx samples. Because of the small number of
      weakly expressed E and e samples, definitive conclusions cannot be drawn on the
      ability of these antibodies to detect these antigens.

PMID- 9018790
TI  - Evaluation of monoclonal anti-D reagents using D variant cells.
AB  - Monoclonal anti-D antibodies submitted to the Third Monoclonal International
      Workshop were evaluated against a number of D variant cells using standard
      serological techniques. The monoclonal antibodies were able to discriminate
      between the cells of Categories Va, VI and DFR but not Category III cells. Cells
      within each category did not give any aberrant results. The Rh:33 cells behaved
      as normal Rh(D) positive cells.

PMID- 9018791
TI  - Results of serological testing of D variants and weak D antigens.
AB  - The report summarizes the results of serological testing of D variants and weak D
      antigens done by our laboratory during the 3rd International Workshop and
      Symposium on Monoclonal Antibodies Against Human Red Blood Cell and Related
      Antigens. In addition we report our findings of variability of the reactivity of
      monoclonal antibodies having apparently identical epitope specificity in
      reactions with weak D antigens.

PMID- 9018792
TI  - Comparative study of 49 anti-D antibodies in tube and gel techniques with 22
      partial D red blood cells.

PMID- 9018793
TI  - Serological investigation of Rh antibodies other than anti-D.

PMID- 9018794
TI  - RHD antigen density and agglutination in RHD variant red cells.
AB  - For the Rhesus categories DIV, DVI, and DVII, agglutination was compared to the
      number of RHD antigens per cell. We detected 3,100 to 15,400 antigens/cell on
      DVI. We report examples of anti-D reactivity showing lack of specificity and
      pointing to the known serologic split in DIV and DVI. Such a split was not found
      in DVII. Other examples were explained by lack of sensitivity. These results
      emphasized the need to consider RHD antigen densities, before a serologic split
      in RHD variant cells is postulated. In this context, flow cytometry may be
      superior to agglutination titers to determine antigen densities.

PMID- 9018795
TI  - Serological analysis of monoclonal anti-E and -e with Japanese E/e variant red
      cells.
AB  - The agglutination patterns have been analyzed for the reaction between 24
      monoclonal antibodies (MAB) with specificity for the Rh antigen E or e and red
      cells of E/e variant from Japanese blood donors. The MABs were tested for direct
      agglutination of papain treated cells at 20 degrees C. The reactions of a full
      titration series of each MAB with a E/e variant cell were compared to the
      reactions of that MAB with normal E + e + cells. Sixteen anti-E were divided into
      a minimum of 6 different agglutination patterns with 8 examples of E variant
      cells. Eight anti-e gave a minimum of 5 different agglutination patterns with 6
      examples of e variant cells.

PMID- 9018796
TI  - A structural model for 30 Rh D epitopes based on serological and DNA sequence
      data from partial D phenotypes.
AB  - Both cDNA RHD sequences and reactivity with monoclonal anti-D have been reported
      in a number of partial D phenotypes, where parts (some epitopes) of the normal D
      antigen are missing, and anti-D of restricted specificity may be made in response
      to challenge with normal D positive blood. This paper analyses these reports
      together and proposes a model for the structure which comprise the epitopes of
      the Rh D antigen. Some epitopes are proposed to be comprised of continuous
      peptide sequence within one extracellular loop, whereas others require
      interactions between two or the extracellular peptide loops.

PMID- 9018797
TI  - Reactions of anti-D monoclonal antibodies with rhesus D variant cells.

PMID- 9018798
TI  - Serological studies of monoclonal RH1(D) antibodies with RH1(D) variants.
AB  - In this paper we chose to emphasize three aspects of our work. First we
      underlined that "low grade and high grade" D weak red blood cells studied at the
      DNA level could, when monoclonal antibodies were used, give patterns of positive
      and negative reactions like partial RH1(D) cells. Secondly, we showed the
      importance of the technical conditions of the study which are essential for
      establishing a pattern of reactivity defining an epitope. It appears that the use
      of papain treated cells at room temperature can be misleading for the definition
      of epitope especially with IgM antibodies. Lastly we pointed out the interest of
      Rh variant cells, defined at the gene level, to study the expression of RH1(D)
      epitopes on the external part of the membrane.

PMID- 9018799
TI  - Coordinator's report on the flow cytometric analysis of the Rh antibodies.
AB  - One hundred and four IgG monoclonal antibodies with specificity within the Rh
      Blood Group System were evaluated by flow cytometry as part of the Third
      International Workshop. Standardisation of data to permit interlaboratory
      comparison of antibody binding was achieved by adherence to a standard red blood
      cell staining protocol, defined control cells and a standard FITC-labelled
      antibody. In addition, calibration standards were provided to permit the
      calculation of Molecules of Equivalent Soluble Fluorochrome (MESF) values from
      the mean channel fluorescence. For the majority of anti-D antibodies mean MESF
      values obtained with D positive cells were far higher than with the negative
      controls (D negative cells), with D variants having intermediate although very
      varied MESFs. In general MESF values obtained with non anti-D antibodies were
      less than for the anti-D antibodies although some of the anti-E antibodies were
      very strong. The highest MESF values were obtained with an anti-CD antibody.

PMID- 9018800
TI  - Flow cytometric analysis of 68 monoclonal anti-D reagents.
AB  - 68 monoclonal IgG anti-D were assessed for quantitative and qualitative binding
      to D variant red cells using a flow cytometric indirect immunofluorescence test.
      One antibody failed to bind to normal RhD pos. cells, but reacted weakly with D
      cat VI and D Cat VII cells. Quantitatively, binding varied approximately twenty
      fold between different MAbs and different D variants. D cat III cells gave the
      lowest level of binding when compared with the D pos. controls. Qualitatively,
      R1VIr, R2VIr, R1VIIr and DFR samples failed to react with various MAbs regardless
      of the levels of binding of these MAbs to the D pos. controls, thus supporting
      the idea of missing epitopes in such variants.

PMID- 9018802
TI  - Evaluation of Rh monoclonal antibodies for flow cytometry tests.
AB  - As participants of the "III International Workshop on Monoclonal Antibodies
      against Human Red Blood Cells and Related Antigens", we tested 43 RH monoclonal
      antibodies by the flow cytometry technique. Besides the anti-D antibodies (not
      included in this paper), we tested the following antibodies: three (3) anti-C;
      one (1) anti-Cw; six (6) anti-c; eight (8) anti-E; three (3) anti-e; two (2) anti
      G; one (1) anti-CcEe (total = 24 antibodies). These antibodies (from different
      lab sources) were tested against antigen positive cells (homozygous or
      heterozygous) and antigen negative cells. When available, some of them were
      tested against "rare" phenotypes like ryr, r' 'Gr, rGr, R2Rz. All the three anti
      C tested, showed poor discrimination between positive and negative cells; from
      the six anti-c tested, only three had good results (Workshop n degree 18, 20, 21)
      with a superior performance of one of them (Workshop n degree 18). From the eight
      anti-E tested, we found two (Workshop n degree 139 and 153) with good
      performance; all the three anti-e were non reactive; the two anti-G failed to
      react with r'r red cells; the anti-Cw reacted better with R1wr cells than R1wR1;
      and the anti-CcEe antibody showed good results with all the phenotypes tested.
      From the 24 antibodies tested, we found six (25%) antibodies with a good
      performance.

PMID- 9018801
TI  - IgG anti-D MAbs in tests by flow cytometry.
AB  - Seventy-two IgG anti-D Mabs were studied by indirect immunofluorescence and flow
      cytometry (FCM) with R1r, rr and various D variant phenotype red blood cells
      (RBCs) (DIIIb,DVI,DVII,Rh33 and uncategorized variant ISBT number 48). The
      results were compared with those obtained by indirect antiglobulin test (IAT).

PMID- 9018803
TI  - RHD epitope density profiles of RHD variant red cells analyzed by flow cytometry.
AB  - For DII and DIVa, RHD antigen sites per cell were tested previously only with a
      limited number of radio labelled anti-D. We determined RHD antigen densities
      (sites/cell) by flow cytometry with 64 anti-D in four partial RHD red cells.
      Epitope densities detected (mean +/- SD) were: DVII 8,000 +/- 1,665 (number of
      anti-D used for calculation: n = 55; percentage of reference cells: 47%); DNU
      (DIIlike) 6,869 +/- 1,381 (n = 47; 29%); and DHMii 20,626 +/- 4,320 (n = 55;
      87%). One DIV cell revealed two peaks with a low fluorescence range of 18,158 +/-
      2,504 (n = 11; 76%) and a high range of 35,477 +/- 2,485 (n = 6; 149%). We
      established epitope density profiles with a large panel of anti-D for four RHD
      variant cells and determined the number of RHD antigens per cell.

PMID- 9018804
TI  - Flow cytometric evaluation of non anti-RH1(D) monoclonal Rh antibodies.
AB  - IgG non anti-RH1(D) monoclonal Rh antibodies were evaluated by flow cytometry.
      The values obtained with these antibodies were less strong than those obtained
      with anti-RH1(D) antibodies. For a significant number of antibodies, the signal
      was not high enough to give reliable results for the antibody specificity.
      Despite these drawbacks, flow cytometry was an efficient tool to appreciate the
      variation of reactivity by different antibodies with normal or variant cells.
      These variations were not always obvious by serological means.

PMID- 9018805
TI  - Coordinator's report: an assessment of the functional activity of human Rh
      monoclonal antibodies after their evaluation by nine laboratories.
AB  - The functional activity of 55 anti-D and 26 MAbs of other Rh specificities was
      determined as part of the Third International Workshop and Symposium on
      Monoclonal Antibodies Against Human Red Blood Cell and Related Antigens. Most
      MAbs were IgG1 (45 anti-D, 16 Rh). There was a large range of anti-D and IgG
      concentrations of the anti-D MAbs (0.4-1680 IU/ml, 1.5-400 micrograms/ml).
      Correlation between quantitative data from different laboratories was good. Six
      laboratories tested the anti-Ds in monocyte ADCC assays. Methods varied greatly,
      especially the effector cells used, the methods of red cell sensitisation, the
      effector to target cell ratio and the assay incubation times. There was some
      correlation of results between most laboratories, but results were better when
      similar assays were performed. The extent of monocyte-mediated haemolysis was
      related to the number of molecules of IgG anti-D bound to the red cells. Monocyte
      phagocytosis assays resulted in a greater variability in results between the four
      evaluating laboratories, though IgG3 MAbs were found more active than IgG1, and
      mostly promoted red cell adherence rather than phagocytosis. Two monocyte
      chemiluminescence assays found comparatively low activity of the IgG3 MAbs; the
      most active IgG1 anti-Ds were MAbs 93 and 95. Correlation between different
      monocyte-mediated assays was generally poor unless the assays were performed by
      the same laboratory. Results of a macrophage ADCC assay showed that the IgG3 anti
      D's promoted greater haemolysis than most IgG1 MAbs. Only two IgG1 anti-D MAbs
      (70 and 104) mediated high haemolysis in this assay. Lymphocyte ADCC assays were
      utilised in four laboratories. The IgG3 antibodies exhibited low activity but one
      IgG1 anti-D (104) consistently mediated high haemolysis. There was no
      relationship between quantitation and haemolysis in this assay. A few MAbs
      exhibited low or no activity in most assays, mainly due to low quantitation. Most
      of the MAbs of non-D specificity mediated low functional activity which in most
      cases was not due to low quantitation. However two MAbs, 24 (anti-CcEe) and 25
      (anti-CD), consistently showed good activity. This study highlighted the great
      variability in assay methodology between the nine participating laboratories,
      which resulted in some apparent differences in functional activity of some of the
      MAbs. The use of standardised methods as well as fewer MAbs tested and
      quantitated at different concentrations may help to determine the relevant
      factors contributing to IgG function.

PMID- 9018806
TI  - Characterization and functional activity of human Rh monoclonal antibodies.
AB  - For quantification of the number of molecules of IgG anti-D bound to RBC, a
      combination of flow cytometry plus Sol-ELISA was found more accurate than Sol
      ELISA alone. However, some Rh MAbs gave very low values of cell-bound IgG using
      flow cytometry. Monocyte-mediated haemolysis correlated well with the number of
      molecules of red cell-bound IgG1 anti-D. The monocyte phagocytosis assay was
      found more sensitive but less quantitative than the monocyte ADCC assay. Most
      monoclonal antibodies mediated little haemolysis by lymphocytes in ADCC assays,
      and haemolysis was not related to IgG concentration, titres or cell-bound IgG.

PMID- 9018807
TI  - Functional (ADCC) study of 54 IgG MAb anti-RhD.

PMID- 9018808
TI  - Anti-Rh(D) monoclonal antibodies: study of their in vitro functional properties.

PMID- 9018809
TI  - Functional activity of Rh monoclonal antibodies in ADCC assay.

PMID- 9018810
TI  - Assessment of monoclonal antibodies by the monocyte-mediated ADCC assay.

PMID- 9018811
TI  - ADCC activity of monoclonal anti-D antibodies.

PMID- 9018812
TI  - A comparison of the functional activity of monoclonal and polyclonal Rh
      antibodies.
AB  - The functional activity of monoclonal anti-Ds has been compared with that of non
      D monoclonal antibodies. Approximately 50% of anti-Ds were more active than a
      positive control while more than 75% of non-D antibodies failed to reach 10%
      activity of the positive control. These figures do not correlate with the IgG
      bound per red cell which, however, does correlate closely with the antigen site
      density as would be expected.

PMID- 9018814
TI  - Rh DNA--coordinator's report.
AB  - Four laboratories contributed to molecular analysis of 66 Rh variant samples
      originating from 12 countries. Most studies were carried out on genomic DNA using
      allele-specific-PCR, PCR-RFLP or nucleotide exon sequencing. In some cases, the
      molecular basis of some new phenotypes was established by DNA sequence analysis
      and the basis for the DVIE haplotypes was revisited.

PMID- 9018813
TI  - Human Rh monoclonal antibodies: assessment of functional activity by
      chemiluminescence and RhD antibody quantitation.
AB  - In vitro cellular assays have been described which are capable of evaluating the
      interactions between sensitised red cells and monocyte or K cells. The
      chemiluminescence assay (CL) has several advantages over other cellular assays
      used to assess functional activity. The CL assay unlike the ADCC assays does not
      require the use of radioisotopes and therefore can be easily integrated into the
      work of a Reference Serology laboratory. The CL assay is an objective test and
      not labour intensive which is the main criticism of the monocyte monolayer assay.
      Seventy-four monoclonal anti-Ds and 29 other Rh specificities have been evaluated
      by a CL assay. The use of the chemiluminescent response produced by
      erythrophagocytosis of sensitised red cells has been shown to correlate well with
      the in vivo response to red cells sensitized with polyclonal IgG antibodies. This
      study aimed at investigating whether the CL assay could identify and
      differentiate monoclonal antibodies that are capable of eliciting a response from
      human monocytes. Poor correlation was obtained between the CL assay results and
      anti-D quantitation (r = 0.236). The chemiluminescence assay discriminated
      between anti-D's with high quantitation levels but low predicted functional
      activity and anti-Ds of low quantitation levels which produced elevated CL
      responses. Only 3 of the 29 non-Rh D specificities tested produced a response in
      the CL assay emphasising the importance of specificity in the functional activity
      of monoclonal antibodies. The demonstration of significant differences in the
      functional capabilities of monoclonal antibodies has important implications for
      reviewing the possible use of monoclonal anti-D preparations for Rh immune
      prophylaxis and highlights the requirement for factors other than the antibody
      concentration to be examined.

PMID- 9018815
TI  - Tentative model for the mapping of D epitopes on the RhD polypeptide.
AB  - The partial D phenotypes correspond to D-positive individuals that may develop
      anti-D antibodies following immunization by transfusion or pregnancy, since they
      lack some of the D epitopes that compose the D antigen. When these red cells are
      tested with a panel of human monoclonal anti-D, different patterns of reactivity
      are observed and at least nine distinct epitopes termed epD1 to epD9 can be
      identified. Molecular analysis of partial D variants have shown that the loss of
      some D epitopes is associated either with intergenic recombination events between
      the D and CE genes generating hybrid gene structures D-CE-D or CE-D-CE, or with
      point mutations of the D gene. Based on these findings, a tentative model that
      correlates critical amino acid positions and D epitope expression on the D
      protein was proposed. Although recent studies suggest that the D antigen may be
      composed of as many as 30 epitopes, the relatively simple model presented here
      may be useful to serologists as a preliminary approach to understanding the basis
      of D antigenic variation in terms of structure-activity relationship.

PMID- 9018816
TI  - Molecular analysis of DVI variant ISBT 35 (R2VIr).

PMID- 9018817
TI  - Rh DNA analysis.

PMID- 9018819
TI  - Molecular analysis of selected Rh variants.

PMID- 9018818
TI  - Molecular biology of partial D phenotypes.
AB  - We have examined all DVI variant phenotypes submitted to the workshop by a
      combination of RT-PCR, multiplex RHD PCR and immunoblotting with Rh antipeptide
      sera. Our findings suggest that all DVI phenotypes arise through hybrid RHD-RHCE
      RHD genes. Genomic DNA derived from all DVI samples were shown to be RHD intron 4
      negative when analysed with an RHD intron 4/exon 10 multiplex assay. We assume
      therefore that all DVI phenotypes involve gene conversion events involving at
      least exons 4 and 5 of the RHD gene. Analysis of a novel D and E variant
      phenotype individual (ISBT49) by RT-PCR has allowed the identification of a
      hybrid Rh gene composed of exons 1-4 RHD: 5 RHCE/D and 6-10 RHD. We propose that
      the partial D & E phenotype observed arises through D & E expression on the
      hybrid RHD-RHCE-RHD protein: as no transcripts encoding Rh E could be found.

PMID- 9018831
TI  - A lightweight ambient air-cooling unit for use in hazardous environments.
AB  - Recent research demonstrated (a) the effectiveness of intermittent conditioned
      air cooling during rest breaks to significantly reduce cumulative heat storage
      and (b) that longer work sessions were possible for individuals wearing chemical
      defense ensembles. To further advance this concept, a strategy for implementing
      continuous air cooling was conceived; ambient air cooling was added during work
      cycles and conditioned air cooling was delivered during rest periods. A compact
      battery-powered beltpack cooling unit (3.9 kg) designed and made at the U.S. Air
      Force Armstrong Laboratory was used to deliver 5.7 L/sec filtered ambient air
      during work cycles: 4.7 L/sec to the body and 1 L/sec to the face. Five
      experimental cycles were conducted in a thermally controlled chamber under warm
      conditions (32 degrees C, 40% relative humidity) with (1) no cooling-intermittent
      work, (2) intermittent cooling, (3) continuous cooling during intermittent
      exercise, and (4) no cooling-continuous work and (5) ambient air cooling during
      continuous exercise. Intermittent, conditioned, and continuous air cooling
      resulted in significant reductions in rectal temperature, mean skin temperature,
      and heart rate as compared with the no-cooling trials. The continuous air-cooling
      trial significantly improved thermal comfort and sweat evaporation. Results
      suggest that ambient air delivered during work cycles by a lightweight portable
      unit (in conjunction with conditioned air delivered during rest periods), can
      definitely improve personal comfort, reduce skin temperature, and decrease the
      cumulative fatigue common to repeated work/rest cycles in selected military and
      industrial applications in which individuals work in chemical defense ensembles.

PMID- 9018832
TI  - Evaluation of two inversion techniques for retrieving health-related aerosol
      fractions from personal cascade impactor measurements.
AB  - Personal cascade impactors are widely used in occupational aerosol exposure
      assessment. Appropriate algorithms must be used to determine the total particle
      size distribution from masses collected on the stages of the cascade impactor.
      Such algorithms should be regarded as integral components of the measurement
      system. When evaluating algorithms for reconstruction of size distributions from
      cascade impactor data, the eventual use of the size distribution must be
      considered. So, from an industrial hygiene perspective, an appropriate basis for
      comparison of given measurement systems is the accurate retrieval of the
      inhalable, thoracic, and respirable aerosol fractions as described by the new,
      internationally accepted, particle size-selective sampling conventions (which are
      expected to form the basis of future aerosol standards). This article compares
      two inversion routines in terms of their abilities to retrieve these aerosol mass
      fractions relative to the masses that would have been obtained using an ideal
      sampler that perfectly followed the sampling convention. The routines were used
      to invert measurements made with the Institute of Occupational Medicine personal
      inhalable dust spectrometer, a miniature cascade impactor that aspirates the
      inhalable aerosol fraction, and the results are presented graphically as contours
      of equal mass bias. The simplest algorithm, based on the a priori assumption of
      lognormality, appears to provide the best results.

PMID- 9018833
TI  - Uptake of polycyclic aromatic hydrocarbons among trainers in a fire-fighting
      training facility.
AB  - The exposure of fire-fighting trainers to polycyclic aromatic hydrocarbons (PAH)
      was assessed by personal air sampling. Uptake of PAH was determined by biological
      monitoring, measuring a metabolite of pyrene, 1-hydroxypyrene, in urine. Eight
      hour time-weighted average concentrations benzo(a)pyrene of 0.029 microgram/m3
      (instructor), 0.045 microgram/m3 (safety officer), and 0.16 microgram/m3 (fire
      assistant) were found. Both tobacco smoking and exposure to smoke from fire
      appeared to be significant sources of increased 1-hydroxypyrene concentrations in
      fire-fighting trainers. There was evidence of exposure and uptake of PAH among
      fire-fighting instructors despite the short time of effective exposure and the
      routine use of protective respirators and protective clothing. Though the uptake
      of PAH was much lower than found in coke-oven workers, who are known to have an
      increased relative risk of cancer, a long-term health risk for fire-fighting
      trainers cannot be excluded. Biological monitoring with urinary 1-hydroxypyrene
      may be useful in tracing highly exposed persons and in monitoring the
      effectiveness of control measures.

PMID- 9018834
TI  - Concentration and size distribution of airborne hexavalent chromium in
      electroplating factories.
AB  - Studies have shown that chromium from electroplating factories can cause
      respiratory problems to workers after prolonged exposure. Since Taiwan has a
      relatively high number of electroplating factories and minimal data regarding
      chromium's effect on workers, the authors undertook this study focusing on the
      size distribution of airborne hexavalent chromium and its concentration levels
      within the factory. Both area and personal sampling were conducted using a
      particle fractionating sampler. Samples were analyzed using visible
      spectrophotometry. A comparison of three types of factories-chromium, nickel
      chromium, and zinc-showed that the highest concentrations were found in chromium
      electroplating factories near the electroplating tank. Hexavalent chromium
      particles obtained from area sampling had mass median diameters between 1.67-6.38
      microns and 0.75-4.73 microns for personal sampling. Particles of this high
      concentration and small size can enter and cause considerable damage to the
      respiratory tract.

PMID- 9018835
TI  - Personal ultraviolet radiation exposure of workers in a welding environment.
AB  - The personal ultraviolet radiation exposure levels of a group of welders and
      nearby workers were estimated using a photosensitive polymer film, polysulphone.
      The polysulphone film was attached to the inner and outer surfaces of eye
      protection, the workers' clothing, and also placed throughout the work area. The
      estimated average ocular exposures (inside the helmets) for welders and boiler
      makers were between four and five times the maximum permissible exposure (MPE)
      limit, and the estimated exposures at the spectacles of nonwelders were around 9
      times MPE. Body exposures (at the clothing surface) for welders were estimated to
      be around 3000 times MPE and for nonwelders around 13 times MPE. The ambient
      ultraviolet radiation levels in the factory were found to exceed the MPE by an
      average of 5.5 times, even in nonwelding areas. The results suggest that welders
      require additional ocular protection to supplement conventional welding helmets,
      and any exposed skin areas of workers in this environment should also be
      protected.

PMID- 9018836
TI  - The use of ergosterol to measure exposure to fungal propagules in indoor air.
AB  - This report concerns the development of a method for the measurement of
      ergosterol in indoor air as a determinant of fungal exposure. Ergosterol was
      determined in spores of 11 species of Aspergillus, Penicillium, and Cladosporium
      selected from the most common molds in 400 homes in Ontario. Spore ergosterol
      content was about 1 microgram/mg, which is the range reported for mycelia, and
      varied by about 25% for the species tested. Ergosterol was determined in bedroom
      air samples taken in the winter in homes in southern Ontario. The median
      ergosterol value corresponded to a total concentration of fungal spores on the
      order of 10 to 10(2) per m3, in the range for other studies where total and
      viable propagules were determined by other methods. The sampling of air for
      ergosterol is a robust method for assessing fungal biomass in air, but provides
      no information on the species present.

PMID- 9018837
TI  - Sabia virus incident at Yale University.
AB  - An incident involving a human exposure to a newly isolated arenavirus, Sabia
      virus, in the Yale Arbovirus Research Unit occurred at Yale University on August
      8, 1994. A senior-level visiting research scientist was exposed to Sabia virus
      while purifying the virus from a large volume of tissue culture fluid. The
      exposure resulted in development of a Sabia virus infection followed by recovery
      of the patient. The incident resulted in a comprehensive review by a Yale faculty
      committee and an external expert committee. As a result, a number of new
      practices and procedures were added to Yale's biosafety policy for investigating
      infectious agents in BL-3 facilities.

PMID- 9018838
TI  - Angles of entry of ultraviolet radiation into welding helmets.
AB  - To investigate the angles of entry of ultraviolet (UV) radiation into welding
      helmets, a UV detector was placed in the eye socket of a head form that was then
      fitted with a range of welding helmets. The head form was exposed to a collimated
      beam of UV radiation from various orientations, and the amount of infiltration
      was measured. Radiation was found to be reflected from the filter plate and into
      the detector (eye) after entering through (1) an opening between the edge of the
      shield and the side of the face, and (2) an opening between the top edge of the
      shield and the top of the head. These results have significance for UV exposure
      when welding is performed in highly reflective and enclosed situations, and for
      the design of welding helmets.

PMID- 9018839
TI  - ELPAT Program report: background and current status (October 1996).

PMID- 9018840
TI  - Industrial hygiene risk assessment: industrial hygiene technology transition.

PMID- 9018841
TI  - Pheromones of the ciliate Euplotes octocarinatus not only induce conjugation but
      also function as chemoattractants.
AB  - Cells of the ten mating types of the ciliate Euplotes octocarinatus communicate
      by pheromones before they enter conjugation. The pheromones induce homotypic
      pairing when applied to mating types that do not secrete the same pheromone(s).
      Heterotypic pairs (i.e., those between cells of different mating types) are
      formed only when both mating types in a mixture secrete a pheromone that the
      other does not. The genetics of mating types is based on four codominant mating
      type alleles, each allele determining production of a different pheromone. Here
      we report that the pheromones not only induce pair formation but also attract
      cells. This was shown by placing cells of various mating types in neighboring
      agar wells so that the pheromones could diffuse from one well to the next. We
      found that the cells accumulated on the side of the well where a pheromone
      entered by diffusion. This response was observed only if the pheromone had the
      capacity to induce the cells to conjugate. That the pheromones and not some other
      substances attract the cells was shown by placing pheromone 3, expressed in
      Escherichia coli, in wells next to tester strains. Mating types known to respond
      to pheromone 3 by pair formation also showed accumulation on the side of the well
      at which the pheromone entered by diffusion. Since the pattern of cell attraction
      corresponds with the pattern of conjugation induction, we suggest that not only
      conjugation induction but also cell attraction is governed by pheromone-specific
      receptors. In addition, we describe a succession of changes in the behavior of
      cells affected by the pheromones.

PMID- 9018842
TI  - The protein phosphatase inhibitor okadaic acid inhibits exit from metaphase II in
      parthenogenetically activated pig oocytes.
AB  - The exposure of in vitro matured pig oocytes to the calcium ionophore A 23187 (50
      microM, 7 min) resulted in parthenogenetic activation in 67% of the oocytes. When
      the activated oocytes were cultured, they formed pronuclei. In these oocytes,
      tubulin labelling revealed a rearrangement of the microtubules into an interphase
      meshwork. The activated oocytes also lost their ability to form cytoplasmic
      asters after short-term taxol treatment. The activation rate of the oocytes was
      further increased when they were cultured with a protein synthesis inhibitor,
      cycloheximide, after ionophore treatment. A culture of ionophore-treated oocytes
      with okadaic acid, the inhibitor of protein phosphatases 1 and 2A, prevents the
      events characterizing oocyte activation. In oocytes cultured with okadaic acid,
      chromatin remained condensed, and cytoplasm retained its ability to respond to
      taxol treatment by the formation of cytoplasmic asters. This effect of okadaic
      acid was observed even in oocytes in which the activating stimulus was followed
      by a culture with cycloheximide. This data allows us to conclude that protein
      phosphatases 1 and 2A play an important role during the transition from metaphase
      II to interphase after activation of the pig oocyte.

PMID- 9018843
TI  - Demonstration, localization, and development of galanin receptors in the quail
      oviduct.
AB  - We recently isolated an oviposition-inducing peptide that was identified as avian
      galanin from the oviducts of the Japanese quail. Avian galanin was localized in
      neural fibers distributed in muscle layers in the uterine and vaginal oviduct
      regions, and potentiated spontaneous contractions of the uterus and vagina. To
      elucidate whether an oviposition-inducing effect of avian galanin is due to the
      direct action on the oviduct, therefore, a specific binding site for avian
      galanin was determined in the functional quail oviduct in this study. The binding
      of [125I]iodoavian galanin was primarily located in the oviduct as well as the
      brain. The galanin binding was specifically inhibited as a function of the
      concentrations of both avian and rat galanins. The specific binding of avian
      galanin to the quail oviduct was temperature dependent and reached the maximum
      level for 1 h at 20 degrees C. In several regions of the oviduct, a higher level
      of specific galanin binding was observed only in the uterus and vagina. In
      contrast, the specific binding was low in the isthmus and negligible in the
      magnum. A similar localization was evident in the functional chicken oviduct. The
      Scatchard plot analysis of the binding of avian galanin to the uterine
      preparation revealed that the dissociation constant (Kd) was 0.249 (95%
      confidence interval, 0.192-0.356) nM, and the number of binding sites was 1.13
      (0.99-1.36) fmol per mg tissue, respectively. During development, the galanin
      binding sites were apparent in the quail oviduct at 3 weeks of age and the number
      of binding sites markedly increased between 3 weeks and 3 months of age. However,
      there was no significant change in the Kd value in the developing quail oviduct.
      This is the first demonstration of the presence of galanin receptors in the
      reproductive tract, such as the uterine and vaginal oviduct. The present results
      suggest that the number of galanin receptors in the oviduct increases during
      development and that galanin acts directly on the mature uterus and vagina to
      induce their contractions. This mechanism may be essential to the avian
      oviposition.

PMID- 9018844
TI  - Stability and change in personality assessment: the revised NEO Personality
      Inventory in the year 2000.
AB  - The Revised NEO Personality Inventory (NEO-PI-R) consists of 30 facet scales that
      define the broad domains of the Five-Factor Model of personality. No major
      revisions of the basic model are anticipated in the near future. Despite their
      popularity, social desirability and inconsistency scales will not be added to the
      NEO-PI-R because their validity and utility have not yet been demonstrated. Among
      possible changes are minor modifications in wording and more extensive
      adaptations for adolescents and for populations with low reading levels.
      Contextualized (e.g., work-related) versions of the instrument will be further
      explored. Many changes are more easily implemented on the computer than the print
      version of the instrument.

PMID- 9018845
TI  - Future directions for the MMPI-A: research and clinical issues.
AB  - The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A; Butcher et
      al., 1992), released in 1992, was developed specifically for use with adolescent
      respondents. The purpose of this article is to offer suggestions concerning 6
      areas of productive research with this instrument. These areas include studies of
      the utility of codetype interpretation, issues related to profile elevation in
      clinical samples, and the identification of criterion for evaluating the
      usefulness of traditional and new MMPI-A scales. Further, these research issues
      also include establishing the optimal age ranges for use with the MMPI-A,
      detecting the effects of the release of a revised instrument on clinician's test
      use patterns with adolescents, and evaluating the optimal methods for the use of
      the MMPI-A Structural Summary interpretative approach. It is noted that these
      research recommendations are by no means exhaustive, and that many other research
      areas should also be investigated in developing a comprehensive research
      literature for this revised instrument.

PMID- 9018846
TI  - Prospects for the assessment of normal and abnormal interpersonal behavior.
AB  - The Interpersonal Adjective Scales (IAS) and the Inventory of Interpersonal
      Problems (IIP) are current representatives of a long-standing tradition and their
      use as assessment instruments is expected to become increasingly widespread in
      the near future and beyond. The IAS is a direct descendent of the interpersonal
      circumplex tradition and is characterized by an extraordinarily close relation
      between theory and method in the assessment of both normal and disordered
      personalities. The IIP stems from a more recent conceptual distinction between
      psychiatric symptoms and problems of living that has been linked directly to the
      interpersonal circumplex. This review is meant to alert clinicians to promising
      supplements to traditional intrapsychic and symptomatic psychodiagnostic
      batteries.

PMID- 9018847
TI  - Parental representations, self-view, and interpersonal functioning of older
      adolescents.
AB  - This study examines the relationship between parental object representations,
      self-representations, and interpersonal relations in a nonclinical sample of
      older adolescents. It was hypothesized that individuals with parental
      representations that are conceptually low, hostile, and rejecting would be
      significantly related to a negative view of self and poor interpersonal
      relations. The results suggest that parental benevolence, ambitiousness, and
      conceptual level are significantly related to interpersonal functioning. Parental
      representations that are qualitatively poor were found to be associated with a
      negative view of self. However, a high conceptual level of mother was noted to be
      significantly related to a negative self-representation. The findings generally
      confirm the nature of the relationship between object representations and self,
      but also suggest that the structural component of parental representations may
      reflect a cognitive component of the self rather than an affective one. The
      difficulties of controlling for depression and method variance issues are also
      discussed.

PMID- 9018848
TI  - Predicting three mood phenomena from factors and facets of the NEO-PI.
AB  - The relationship between transient mood phenomena and enduring personality
      characteristics was studied. Eighty-one women completed the NEO Personality
      Inventory (Costa & McCrae, 1985) and provided daily unidimensional mood ratings
      for 20 days. Average mood was negatively related to Neuroticism (N) and
      positively related to Extraversion (E). More fine-grained analyses revealed that
      Positive Emotions, a facet of E, was a better predictor of average mood than was
      the overall E factor score. The greater a facet's loading on N or E, the better
      it predicted average mood. Within-day mood variability (mood fluctuation) was
      positively related to Openness to Experience (O), particularly to the facet,
      Fantasy. Across-day variability (mood swing) was positively related to both E and
      O. No relationship was found between any of the mood variables and Agreeableness
      (A) or Conscientiousness (C). The 3 mood variables were virtually independent of
      one another, but each showed moderately high temporal stability across the 4-week
      period.

PMID- 9018849
TI  - Predicting treatment attendance and weight loss: assessing the psychometric
      properties and predictive validity of the Dieting Readiness Test.
AB  - The Dieting Readiness Test (DRT) has been recommended by the Institute of
      Medicine as a measure of diet and exercise-related motivation and attitudes in
      those about to embark on a weight loss program. However, little research is
      available regarding the psychometric properties of this instrument. We conducted
      a study to assess the psychometric properties and predictive validity of the DRT.
      A group of 410 obese adults seeking outpatient treatment at a university-based
      weight management center completed the DRT prior to engaging in a comprehensive
      medically monitored program. Principal-components factor analysis indicated a
      five-factor solution and acceptable internal consistency for the resulting
      scales. The Bingeing and Eating cues scale was negatively associated with program
      attendance. None of the four remaining scales correlated with either attendance
      or weight loss. We conclude that although the DRT possesses a stable and
      interpretable structure and adequate internal consistency, it does not appear to
      be a strong predictor of weight loss or treatment attendance.

PMID- 9018850
TI  - Rorschach interpretation with high-ability adolescent females: psychopathology or
      creative thinking?
AB  - Highly intelligent and creative persons have long posed interpretation
      difficulties for users of the Rorschach Inkblot Test. This study examined Exner's
      (1993) Schizophrenia, Depression, and Coping Deficit indices as adjustment
      measures in a sample of 43 female adolescents enrolled in an early college
      entrance program and a comparison group of 19 girls enrolled in public high
      school gifted programs. Contrary to conventional interpretation, higher scores on
      the Rorschach Schizophrenia Index among the accelerants were correlated with
      healthy emotional adjustment on both the California Psychological Inventory and
      the Self-Perception Profile for Adolescents (SPPA). Further analyses offered
      support for the hypothesis that among accelerants, elevated scores on the
      Rorschach constellations did not indicate psychopathology, but rather their
      creative thinking style.

PMID- 9018851
TI  - Personality and depression: a validation study of the depressive experiences
      questionnaire.
AB  - This study investigated the validity of Blatt's model of depression as indicated
      by his operational measure of its constructs via the Depressive Experiences
      Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976). Hypothesized relations
      between the two relevant scales of the DEQ and Tellegen's (1982) Multidimensional
      Personality Questionnaire (MPQ) were examined. Participants consisted of 195
      women, including 67 hospitalized unipolar depressives, 77 never-hospitalized
      unipolar depressives, and 51 nonpsychiatric controls. Overall, the results
      partially supported the validity of the DEQ even though all participants were
      women and prior studies have indicated the DEQ's greater discriminative validity
      for men than for women. However, several of the most strongly predicted
      relations, such as between DEQ Self-Criticism and MPQ Achievement were not
      confirmed. Coherent, significant relations between scales of the two measures
      remained after partialling out the effects of severity of depression.

PMID- 9018852
TI  - Implications of the people = male theory for the interpretation of the Draw-A
      Person Test.
AB  - Researchers in the language and social-cognitive fields have suggested that
      social mores and the use of masculine generic grammatical terms such as he and
      man have resulted in a people = male bias. This information processing bias
      causes most people to attribute male gender to a gender-unspecified person. Male
      gender appears to be prototypic of the person construct or category. These
      research findings have implications for the interpretation of the Draw-A-Person
      Test (Machover, 1949).

PMID- 9018853
TI  - Antisocial personality by proxy: the Norton-Sims syndrome.
AB  - An antisocial personality disorder by proxy is defined by a proposed set of
      diagnostic criteria and a general description of proxy and perpetrator
      characteristics. Subtypes, dynamics, and features of this proposed disorder are
      described, and five-factor personality model (Costa & Widiger, 1994) loadings for
      the proxy and perpetrator are hypothesized. The relationship to abuse trauma and
      the five-factor personality model are discussed along with implications and
      suggestions for future research.

PMID- 9018854
TI  - A comparison of the effects of sacred and secular music on elderly people.
AB  - Two kinds of music, sacred and secular, were played to elderly participants and
      rated by them on various aspects of evoked feelings. Additionally, pre- and
      posttest batteries of questionnaires were administered to measure the
      spirituality and ego integrity of the listeners. Statistical analyses of the
      findings failed to reveal significant effects on the spirituality of the
      participants, although the two kinds of music were rated differently. When
      results for all the music were combined, a significant and positive correlation
      was found between the spirituality scores of the listeners and the ratings of
      both kinds of music for reverence or spirituality. Most participants found the
      selections restful and evocative for memories and thoughtfulness. Music of the
      type used in this study may have potential value as an accompaniment for
      techniques such as life review and relaxation therapy.

PMID- 9018855
TI  - Attachment and the representation of intimate relationships in adulthood.
AB  - Community college students in the United States (151 men, 217 women) described
      their current or most recent intimate relationship on questionnaires derived from
      the Structural Analysis of Social Behavior (Benjamin & Friedrich, 1991).
      Attachment organization was assessed by categories (secure, avoidant, or
      ambivalent) and by dimensions (Attachment Security x Level of Activation).
      Respondents with avoidant or ambivalent attachment described more hostility in
      their relationships than secure participants did. Avoidant participants described
      themselves as less submissive. Respondents with low attachment security and high
      attachment activation were especially likely to describe more hostile patterns of
      interaction. Those with greater attachment security also described more
      interdependence in the relationship. No interaction effects of attachment with
      amount of experience in close relationships were found.

PMID- 9018856
TI  - Coping with job loss: an attributional model.
AB  - Coping strategies used by workers who have been laid off are examined in the
      context of attributions, particularly workers' causal attributions. Different
      categories of attributions are linked to subsequent strategies for coping.

PMID- 9018857
TI  - The relationship between job involvement and well-being.
AB  - Researchers have reported contradictory relations between job involvement and
      well-being. In this study, a differentiation was made between job involvement
      based on need congruence and the resulting need fulfillment in one's job and job
      involvement not based on this concept. Participants were 383 women and 50 men.
      Job involvement based on need congruence was related to a high level of well
      being or was negatively related to it. The mean levels of the two kinds of
      involvement were equal. Results suggest that job involvement is related to well
      being only if the constructs are based on equal processes-that is, on need
      congruence in one's job.

PMID- 9018858
TI  - Comparison of recent graduates of clinical versus counseling psychology programs.
AB  - Recent graduates from clinical (N = 65) and counseling (N = 64) psychology
      programs were surveyed to assess similarities and differences of aspects of their
      programs and job-related activity. Results revealed only minor differences.
      Counseling psychologists were more likely to provide group therapy, career
      counseling and assessment, public lectures and workshops, to have more knowledge
      of the Strong Interest Inventory, to be more likely to work in university
      counseling centers, and to endorse humanistic theoretical orientations. Clinical
      psychologists were more likely to work in medical school settings, to ascribe
      human behavior to internal states rather than to social causes, and to have
      greater knowledge of the Rorschach. However, the similarities between the two
      specialities relative to work setting, theoretical orientation, service,
      research, and teaching activities, far outweighed these minor differences.
      Implications of these findings are placed in the context of previous research
      that has suggested the possible merger of the two specialities.

PMID- 9018859
TI  - Analysis of affiliation-related traits in terms of the PAD Temperament Model.
AB  - Affiliation-related traits were explored using findings relating to the
      Affiliative Tendency (MAFF) and Sensitivity to Rejection (MSR) scales and 3
      nearly independent dimensions of the PAD Temperament Model: trait pleasure
      displeasure (P), trait arousability (A), and trait dominance-submissiveness (D).
      Summary equations showed that Affiliative Tendency involved pleasantness and
      arousability [.66P + .34A], whereas Sensitivity to Rejection was mostly
      submissiveness [.15A - .85D]. Dependency resembled affiliative tendency but also
      included submissiveness [.26P + .30A - .44D]. Emotional empathy also resembled
      affiliative tendency but emphasized arousability over pleasantness [.30P + .70A].
      Conformity consisted only of submissiveness. Loneliness [-.77P - .23D] resembled
      boredom and depression. Popularity, moderately opposed to loneliness [.45P + .17A
      + .38D] resembled the MAFF augmented by dominance. Shyness [-.30P + .13A -.57D]
      resembled anxiety and neuroticism.

PMID- 9018860
TI  - Laboratory pain and styles of coping with anger.

PMID- 9018861
TI  - Personality characteristics of persons addicted to heroin.

PMID- 9018862
TI  - Chronic traumatic wounds of the leg.
AB  - The authors report the results of a retrospective study of the treatment of
      chronic defects of soft tissues and bones of the leg and foot with free muscle
      and musclecutaneous flaps. The study deals with the results of the use of the
      microsurgical techniques during the period of 11 years at the Department of
      Plastic Surgery of the 3rd Medical School in Prague. Discussed are the advantages
      and disadvantages of this technique as one the of possible therapeutic methods
      inclusive of the results obtained at the above mentioned department.

PMID- 9018863
TI  - Treatment of defects and instable skin scars on heavily exposed parts of the leg.
AB  - The authors report a series of 41 patients subjected to a transfer of the
      sensitive fasciocutaneous flap to a defect or to instable skin scars on the leg.
      Described are immediate as well as longterm surgical results in relation to the
      sensitivity of the transferred flap and the condition of the donnor site of the
      flap.

PMID- 9018864
TI  - Caudal trapezius composite island flap for extensive shoulder defects.
AB  - The trapezius composite flap was first described by Demergasso in 1979 (2). The
      caudal trapezius island flap was described by Mathes and Nahai (4), in head and
      neck cancer reconstruction. Baek and Biller (1) described the descending branch
      of the transverse cervical artery, as a dominant blood supply. It is an useful
      flap for the reconstruction of defects around shoulder, neck and cheek regions.
      The anatomy of the trapezius muscle, its blood supply, vascular territories and
      its function is described in brief. Use of this flap in the reconstruction of
      compound extensive tissue defects in shoulder region of our patient is presented.

PMID- 9018865
TI  - Caput mandibulae accessorium.
AB  - The presented anomaly consists of a doubled mandibular condylus in a boy aged 5.5
      years. We report this case because of its rare localisation, shape, size and
      microscopic pattern. It represents a doubled articular process arising from the
      mandibular processus coronoideus. From the morphologic view the finding is very
      exceptional. We failed to find any similar case in the literature available. The
      findings of doubled articular processes (condylus bifidus) previously quoted are
      of different origin. In this case it was obviously disorder in the
      differentiation of the mandible within the period when the mandibular ramus basis
      was formed by the secondary cartilage.

PMID- 9018866
TI  - Care of patients with facial clefts at the Department of Plastic Surgery in
      Prague.
AB  - The multidisciplinary care of cleft defects in the Prague Department of Plastic
      Surgery has a long tradition. The authors describe the team care of patients
      including the timing of the surgery as well as the conservative therapy.

PMID- 9018867
TI  - Construction of neophallus in male pseudohermaphroditism.
AB  - Eight patients with male pseudohermaphroditism were treated between the years
      1988-1994. They showed various physical-sexual anomalies. In 4 patients the
      existing penis was lengthened, the urethra was created and the split scrotum was
      fused. In the 4 remaining patients a new penis was created from lateral groin or
      abdominal tubed or skin-gracilis flaps, and made rigid by means of a silicon
      implant. The scrotum was reconstructed. The results were satisfying. On the basis
      of our own experience it may be said that the reconstruction of genitals must be
      planned individually, depending on the abnormalities in the physical-sexual
      development and the psycho-sexual orientation of the patient.

PMID- 9018868
TI  - The influence of ethyl alcohol on the development of the chondrocranium of Gallus
      gallus.

PMID- 9018869
TI  - The temple of health. A pictorial history of the Battle Creek Sanitarium.

PMID- 9018870
TI  - Engineering minibody-like ligands by design and selection.

PMID- 9018871
TI  - Antibodies against HIV-1 from phage display libraries: mapping of an immune
      response and progress towards antiviral immunotherapy.

PMID- 9018872
TI  - Chemical engineering at the antibody hinge.

PMID- 9018873
TI  - Structure and function in IgA.

PMID- 9018874
TI  - IgG effector mechanisms.

PMID- 9018875
TI  - Glycosylation of antibody molecules: structural and functional significance.

PMID- 9018876
TI  - Engineering novel antibody molecules.

PMID- 9018877
TI  - Ligand function of antigenized antibodies expressing the RGD motif.

PMID- 9018878
TI  - Immunogenicity of viral epitopes expressed on genetically and enzymatically
      engineered immunoglobulins.

PMID- 9018879
TI  - The Commonwealth Dental Association.

PMID- 9018880
TI  - Dental caries, fluorosis and the cosmetic implications of different TF scores in
      14-year-old adolescents.
AB  - The aims of this study were to determine the opinions of a group of adolescents
      about the cosmetic acceptability of a range of fluorosis, investigate the
      prevalence and severity of fluorosis in the sample and consider the extent to
      which fluorosis levels were related to their dental caries experience. A random
      sample of 534 14-year-old pupils from the non-fluoridated industrial city of
      Manchester were examined for caries and fluorosis. Each subject then examined six
      photographs of upper anterior teeth showing a range of TF scores 0-4 and were
      asked to rate the appearance of each as either very poor, poor, acceptable, good
      or very good and to indicate whether they would request treatment if their teeth
      were so affected. Four hundred and seventy-six subjects (89 per cent) had TF
      scores of 0. Of the 58 subjects (11 per cent) with fluorosis, 27 (5 per cent)
      scored TF = 1; 22 (4 per cent) TF = 2; 7 (1 per cent) TF = 3 and one subject
      scored TF = 4. The subjects who had no fluorosis had a mean DMFT of 3.0 which was
      significantly higher than the mean of 2.2 among those with any fluorosis. The
      proportion of subjects who rated the photographs as poor or very poor fell from
      29 per cent for TF score 0 to 15 per cent for TF score 2 and then increased to 92
      per cent for TF score 3. The responses of the subjects regarding their desire for
      treatment matched closely with their opinions on appearance; the majority of
      subjects expressed concern over the appearance of teeth with TF scores of 3 and
      higher. It is concluded that the prevalence of aesthetically objectionable dental
      fluorosis was low and that mild fluorosis was associated with a lower risk of
      dental caries and a more acceptable appearance. It is essential that a balanced
      view of the relative benefits and risks of the use of fluorides is maintained and
      proven benefits are not overwhelmed by largely unfounded aesthetic concerns.

PMID- 9018881
TI  - Use of self-report postal questionnaires for district-based adult oral health
      needs assessment.
AB  - Self-report postal questionnaires have been advocated as an efficient means of
      collecting local data on adult oral health needs. The aim of this study was to
      compare the response from deprived and affluent communities and examine a method
      for the detection and compensation of non-response bias. An oral health status
      questionnaire was administered by post to random samples of older residents from
      affluent and deprived electoral wards. The survey was conducted in three distinct
      stages to increase the response rate and to quantify the effects of non-response.
      A response of 59.6 per cent was achieved from the deprived ward and 77.7 per cent
      from the affluent ward, this difference was statistically significant. The
      response rate compared favourably with contemporary national and international
      studies of oral health using postal survey methods. The pattern of response over
      the three stages was used to detect the presence and direction of non-response
      bias. This analysis showed evidence of non-response bias for only one variable of
      interest, for which an estimated prevalence value was calculated.

PMID- 9018882
TI  - Oral health in alcohol misusers.
AB  - One hundred and seven chronic alcohol misusers (mean age 42.9 years; range 21-65
      years; 80 males) attending four centres in South East London were interviewed on
      their current and past alcohol consumption. Their nutritional status (body mass
      index (BMI) and mid arm muscle circumference) was also recorded. Each subject
      completed a dental and oral mucosal examination. Ninety four per cent of the
      sample consumed greater than 50 units of alcohol per week and 80 per cent greater
      than 100 units of alcohol per week. Smoking and alcohol misuse were found to be
      related, 81 per cent reporting both habits. Neither plaque index scores or mean
      subject pocket depths were correlated with alcohol consumption but both were
      positively correlated with the frequency and duration of smoking. Overall mean
      DMFT was 15.4; age specific mean DMFT and tooth loss of the sample were closely
      similar to the 1988 United Kingdom adult dental health survey data. The
      prevalence and severity of tooth wear and attrition were greater in the sample
      than levels described in the literature and these dental features may prove
      useful markers to the practitioner. Trauma to teeth and oral mucosae was noted in
      25 per cent of the sample. Seven oral mucosal lesions (including one treated
      carcinoma) were detected; mucosal trauma could have acted as a co-factor.
      Furthermore, 21 per cent of the alcoholics were malnourished (BMI < 20). It is
      concluded that, unlike several reports from the United States, dental health in
      this sample of alcoholics is not compromised; however mucosal health is a cause
      for concern.

PMID- 9018883
TI  - Prevalence of developmental enamel defects and dental caries in rural pre-school
      Thai children.
AB  - The prevalence of developmental enamel defects and dental caries was assessed in
      344 Karen children aged 1-4 years who were chronically (70 per cent) and acutely
      malnourished (9.3 per cent) The teeth were cleaned with gauze to facilitate
      detection of hypoplastic lesions on labial surfaces of maxillary incisors. At
      least one tooth with defective enamel was seen in 31.9 per cent of children,
      while enamel hypoplasia was present in 22.7 per cent of children. Enamel defects
      were found in 21.2 per cent of teeth, with hypoplasia and opacities occurring in
      14.6 and 6.6 per cent of teeth, respectively. Gender did not alter the prevalence
      of defects. The upper central incisors were affected more than lateral incisors.
      The prevalence of dental caries was 31.9 per cent with a mean dt of 1.1. The
      prevalence of caries associated with enamel hypoplasia was significantly greater
      than that associated with opacities and sound enamel (P < 0.0005).

PMID- 9018884
TI  - Index of Orthodontic Treatment Need, its use in a dental epidemiology survey
      calibration exercise.
AB  - The Index of Orthodontic Treatment Need (IOTN) was included in a pre-survey
      calibration exercise of 18 dental epidemiologists. Nine months later 16 of the
      epidemiologists were re-calibrated in the IOTN. The Index was readily accepted by
      the experienced dental epidemiological examiners and each examination was
      estimated to be extended by, on average, less than two minutes. The inter
      examiner agreement of the dental health component using the weighted kappa
      statistic improved from a mean of 0.53 (moderate agreement) for the first
      calibration to 0.66 (good agreement) at the second calibration. The mean inter
      examiner agreement on the aesthetic component using the weighted kappa statistic
      reduced from 0.52 for the first calibration to 0.49 at the second. Using
      sensitivity and specificity to measure agreement on the dichotomous decision of
      those defined as having a definite treatment need, mean sensitivity rose from
      0.72 to 0.79 and specificity from 0.90 to 0.97. It is concluded that dental
      examiners for epidemiological surveys can be trained to use the IOTN by using a
      pre-calibration exercise and that agreement on the dental health component
      improves after the index has been used for some months.

PMID- 9018885
TI  - Lack of knowledge among parents, of the implications of receiving orthodontic
      treatment.
AB  - In a survey of parental knowledge of the complications of orthodontic treatment
      it was surprising to find how few 'experienced' parents knew that dental decay
      could occur beneath an appliance or that, after treatment ceased, there might be
      some relapse. Experienced parents were defined as those who had children who had
      received or were receiving treatment, or who had been patients themselves. Self
      administered questionnaires were delivered to 600 parents of 9-year-old children
      randomly selected from school rolls in two areas of South East England. Among the
      430 replies received, 123 were from parents with experience of orthodontic
      treatment. Only 41 per cent of them knew that decay could occur beneath a fixed
      appliance and less than a third that relapse could occur after treatment ceased.

PMID- 9018886
TI  - Missing teeth and lost teeth of adults aged 30 years and over in south-western
      Finland.
AB  - The majority of Finnish adults have lost one, some or all of their teeth. The
      prosthetic replacement of missing teeth has thus been an important element of
      adult dental care. However, there have been no longitudinal studies focusing on
      the development of oral health among the Finnish adult population in terms of
      further tooth loss. A baseline sample from 1977-78 was selected from the city of
      Turku to represent the adult population aged 30 years and over. Ten years later,
      a follow-up examination was carried out on this baseline study group. A new
      sample of persons aged 30-39 years was also obtained to provide cross-sectional
      information, allowing comparisons between this study group and the youngest age
      group of the 1977-78 study. In 1977-78, 52 per cent of all subjects had 20 or
      more remaining teeth. The mean number of missing teeth was 15.8 (SD 11.05) and
      the corresponding median 12 teeth. The number of missing teeth was on average
      higher in the older age-groups (P < 0.001). Women had more missing teeth than men
      (P < 0.01). In the ten-year follow-up study, the mean number of lost teeth was
      1.5 (SD 2.32) and the median one tooth. The average number of lost teeth
      increased with age (P < 0.01). The rate of tooth loss was highest for those with
      10 to 19 teeth at baseline, second highest for those with one to nine teeth and
      lowest for those with 20 to 32 teeth (P < 0.001). The reasons most often reported
      for tooth extraction were tooth mobility, pain and prosthetic treatment. In the
      cross-sectional study groups of persons aged 30-39 years, the proportion of
      subjects with a complete natural dentition of 28 to 32 teeth was 63.4 per cent in
      1989, compared with 40.0 per cent ten years earlier. The average number of
      missing teeth was lower in 1989 than in 1977-78 (mean 4.7, SD 3.81 vs. mean 7.8,
      SD 6.92; P < 0.001). In both cross-sectional examinations women had a higher mean
      number of missing teeth than men. However, the difference between the genders was
      statistically significant only in 1977-78 (P < 0.01). Among the age-group of 30
      39 years, there has been a considerable improvement in retention of natural teeth
      during the ten-year interval. However, among the middle-aged and elderly
      population reduced dentition was common; in addition, extraction was still used
      as a dental treatment especially among persons with reduced dentition. This
      suggests that the need for prosthetic replacement of lost teeth will continue to
      play a role in adult dental care in Finland for some decades to come.

PMID- 9018887
TI  - Prevalence of third molars in dental practice attenders aged over 35 years.
AB  - There is a lack of information in the United Kingdom on the prevalence of third
      molars in older patients. The aim of this study was therefore to define the
      pattern of lower third molar retention in UK dental practice attenders aged 35
      years and over. A random sample of 599 eligible patients from a rural dental
      practice were included in the study. Information was obtained from clinical notes
      and panoramic radiographs. Data collected included age, gender, presence or
      absence of lower third molars, number of teeth present in the lower arch and
      eruption status. Two hundred and sixty-four (44.1 per cent) had at least one
      lower third molar present (mean age = 57.1 years) while 335 (55.9 per cent) had
      no lower third molars (mean age = 50.2 years). The data suggest that a greater
      proportion of men than women retain at least one lower third molar although this
      finding was not statistically significant. Seventy per cent of retained lower
      third molars reported in the study were fully erupted. Sixty per cent were
      vertically placed. There was an association between age and number of teeth
      present (chi 2 = 38.85, 4DF, P < 0.05), older patients having fewer lower teeth.
      These data suggest that a large number of patients can expect to keep their lower
      third molars beyond the age of 35 years and that in many cases a conservative
      "wait and see' policy for lower third molars in the early twenties is
      appropriate.

PMID- 9018888
TI  - A quality assurance review of the patient referral process and user satisfaction
      of outpatient general anaesthesia services for dental treatment.
AB  - In many parts of the United Kingdom the Community Dental Service (CDS) receives a
      consistently high level of referrals for general anaesthetic (GA) provision from
      general dental practitioners (GDPs), predominantly for the treatment of pain in
      young children. To provide a safe and effective service it is essential to have
      an appropriate and satisfactory referral process. As part of the established
      quality assurance programme in the East Kent CDS two surveys utilising self
      complete postal questionnaires were conducted, the first to assess GDP's opinions
      and to examine their referral procedure, the second to gauge user satisfaction
      with the overall care provided by the CDS-GA service. The main findings suggested
      a lack of effective communication both between health professionals and with
      their patients. Over 80 per cent of the GDPs considered either the existing CDS
      referral guidelines needed clarification or did not even know such guidelines
      existed. Parents of referred children reported a high level of satisfaction with
      the service provided by the CDS, but some were critical of a lack of immediate
      access for children in pain. The finding of greatest concern was that 50 per cent
      of the parents stated their child's GDP did not explain the possible risks of
      general anaesthesia prior to referral and 70 per cent were offered no alternative
      form of treatment to a general anaesthetic. The results of this study should be
      fed into the continuing quality assurance programme to enable the effective and
      appropriate development of the CDS-GA service.

PMID- 9018889
TI  - Toothbrushing schedule, motivation and 'lifestyle' behaviours in 7,770 young
      adolescents.
AB  - Data from a survey of 7,770 14-15-year-old children from 131 secondary schools
      throughout England were analysed to obtain information about the times of day
      they brushed their teeth, their motivation for toothbrushing, and some
      'lifestyle' variables. In the 19 per cent of respondents who reported brushing
      their teeth once per day, 75 per cent did so in the morning before school; only
      23 per cent reported brushing before going to bed at night. In this group there
      was a marked association between reported readership of broadsheet newspapers and
      reported time of brushing in the daily schedule. As reported newspaper readership
      changed towards the popular tabloids, the proportion of subjects who reported
      brushing only in the morning increased. Almost all those who claimed to brush two
      or three times per day reported brushing before bed. There were systematic
      differences in motivation for toothbrushing: those who reported brushing only
      once per day appeared to be motivated more by social reasons than by preventive
      dental health reasons. Among other factors, toothbrushing appeared to be
      influenced by getting up time, breakfast, and time of going to bed. The results
      demonstrate that toothbrushing habits are strongly influenced by an individual's
      lifestyle and social behaviour. Dental health advice needs to take into account
      this broad pattern of background factors.

PMID- 9018890
TI  - Caries experience of 35-year-old Oslo residents and changes over a 20-year
      period.
AB  - The dental health of 35-year-old Oslo citizens was investigated in cross
      sectional studies applying similar methods in 1973, 1984 and 1993. In the 1993
      investigation, a clinical and radiographic examination of dental caries was
      performed on 121 randomly selected individuals (response rate 68 per cent).
      DMFT/S scores were used for recording caries experience. Carious surfaces (DS)
      were related to independent variables organised under the four main categories of
      health field concept; environment, behaviour, biology and health care. Mean DMFS
      based on 28 teeth was 40.9 in 1993, compared to 66.5 in 1984 and 68.2 in 1973.
      DS, MS, FS and DMF values were significantly lower in 1993 compared with those
      from the previous 1973 and 1984 studies, while only minor differences were
      detected from 1973 to 1984. High numbers of decayed surfaces (DS) were
      significantly associated with poor oral hygiene, unsatisfactory economic status
      and irregular dental visiting habits. The most influential independent variables
      explained 35 per cent of the variance in carious surfaces (DS).

PMID- 9018891
TI  - The role of laparoscopic ovarian biopsy in the management of premature gonadal
      failure.
AB  - Approximately 1% of women enter menopause before 40 years of age. This premature
      event, however, is not as consequential when women have completed their
      reproductive lives as when they desire another pregnancy. When this latter
      situation does arise, the question facing the clinician is whether the ovaries
      still have follicles (resistant ovary syndrome) or they are depleted of these
      primordial follicles (premature menopause). The only way to demonstrate the
      presence of or absence of primordial follicles in the ovaries is by obtaining an
      adequate biopsy specimen for histopathologic diagnosis, a procedure that can be
      done via laparoscopy. This study had two purposes: one was to determine whether
      laparoscopic ovarian biopsy can provide an adequate specimen for histopathologic
      diagnosis safely and with low complication rates, and the other, to ascertain the
      relative frequency of premature menopause and resistant ovary syndrome.

PMID- 9018892
TI  - Cancer screening in primary care: strategies for your office. A program of the
      Connecticut Division of the American Cancer Society.
AB  - Primary-care physicians' compliance with cancer screening guidelines has been in
      general unsatisfactory. Mailings have not had the desired effect upon these busy
      physicians who are preoccupied with many other issues. The Ohio Division of the
      American Cancer Society developed a program of in-office cancer screening
      education of primary-care physicians which resulted in a significant improvement
      in compliance to cancer screening guidelines. The Connecticut Division of the
      American Cancer Society has pursued this concept with their own program of visits
      targeted at physicians and their office staffs. A description of this program,
      which is still in its initial phases, is presented. The impact will be evaluated
      in due time, however additional volunteers to conduct these visits are needed.

PMID- 9018893
TI  - Indinavir: a pharmacologic and clinical review of a new HIV protease inhibitor.

PMID- 9018894
TI  - Napoletano vs CIGNA: an evolving standard of MCO legal compliance?

PMID- 9018895
TI  - Healers not hit men.

PMID- 9018896
TI  - The industrialization of medicine.

PMID- 9018897
TI  - In response to Dr. Deren's "hares and hounds".

PMID- 9018899
TI  - Physician-assisted suicide and euthanasia.

PMID- 9018900
TI  - Dementia, insight, and suicidal behavior.

PMID- 9018901
TI  - Suicide and crisis intervention in rural communities in Sri Lanka.

PMID- 9018902
TI  - Improving treatment compliance among adolescent suicide attempters.

PMID- 9018903
TI  - Hotlines as discrete services. Part 2.

PMID- 9018905
TI  - Evaluation strategy for Finland's suicide prevention project.
AB  - Finland's suicide prevention project (1987-1996) has proceeded to its final
      phase, evaluation. In this article the general structure of the evaluation and
      the strategy for evaluating the implementation phase (1992-1996) are presented.
      The evaluation aims to look at the success of the project in its target areas and
      the critical factors involved. It deals with the intervention strategies evolved,
      as well as indicators of progress in suicide prevention activities. A process
      evaluation approach is used to evaluate the national strategy and the project.
      The first follow-up (1993) and preliminary results from the ongoing evaluation
      (1996) show that the project is being largely successful in meeting the operative
      challenges formulated in the national strategy.

PMID- 9018904
TI  - Alcohol problems among suicide attempters in the Nordic countries.
AB  - The purpose of this study was to see whether and how the number of suicide
      attempters with alcohol problems and their drinking habits differ between the
      Nordic areas under study. Problem-drinkers were defined as persons who themselves
      felt that they had an alcohol problem. The analyses were based on data collected
      at five Nordic research centers participating in the WHO/Euro Multicentre Study
      on Parasuicide, namely: Helsinki (Finland); Umea and Stockholm (Sweden); Slr
      Trlndelag (Norway); and Odense (Denmark). The results showed that the frequency
      of problem-drinking among suicide attempters differed markedly between the areas
      under study; the Finnish male and the Danish female suicide attempters included
      the highest proportions of self-identified problem-drinkers. The pattern of
      drinking among the suicide attempters also differed between the areas. The
      analyses indicate that the point when alcohol becomes a problem to somebody,
      especially to a degree that it increases the risk of suicidal behavior, not only
      depends on how much and how often the person drinks alcohol; the prevailing
      drinking pattern, the attitudes towards drinking alcohol, and the level of social
      control are also important factors to take into consideration when relations
      between alcohol and suicidal behavior are under study.

PMID- 9018906
TI  - Opioid addiction and suicidality.
AB  - The prevalence of suicide attempts among opioid addicts is reported to lie
      between 8% and 17%, with some studies reporting an even higher rate among special
      groups of addicts. Yet there is insufficient knowledge about which addicts have a
      higher risk of suicide and which other factors seem to be involved in the
      constellation leading to the suicide attempt; the study of different subgroups of
      addicts is thus necessary. This paper reports a study on suicide attempts among a
      sample population in a detoxification unit and another group undergoing codeine
      maintenance treatment. There was a high rate of suicide attempts among both
      groups (23% of those in the detoxification unit and 28% of those maintained on
      codeine), but treating physicians tended to underestimate suicidality. The
      results lead to the conclusion that among a subgroup of addicts suicidality plays
      a larger role; a greater emphasis should thus be placed on the underlying
      psychopathology and the treatment needed.

PMID- 9018907
TI  - Suicide trends in County Mayo Ireland: a brief report.

PMID- 9018908
TI  - Developing a European Network for suicidology.

PMID- 9018909
TI  - Reaction to: "Preventing suicide in women and men," by David Lester (Crisis 1995;
      16:79-84)

PMID- 9018910
TI  - A response to Lanny Berman's letters across the Atlantic (tenth letter in a
      series)

PMID- 9018911
TI  - Lymphoma of the thyroid gland.

PMID- 9018912
TI  - Histogenesis of thyroid C-cell carcinoma.

PMID- 9018913
TI  - Advances in immunocytochemistry of thyroid tumours 1987-1994.

PMID- 9018914
TI  - Minimally invasive follicular thyroid carcinoma: a clinico-pathological study.

PMID- 9018915
TI  - Poorly differentiated carcinoma of the thyroid: an aggressive type of tumour
      arising from thyroid follicular epithelium.

PMID- 9018916
TI  - Surgical strategies in papillary thyroid carcinoma.

PMID- 9018917
TI  - Growth factors in thyroid cells.

PMID- 9018918
TI  - Thyroid carcinoma: interrelationships between local thyroid hormone metabolism by
      the type I 5'-deiodinase and the expression of thyroid hormone receptors and
      other thyroid-specific (de-)differentiation markers.

PMID- 9018919
TI  - Transcytosis of IgG from the basolateral to the apical membrane of human
      thyrocytes in autoimmune thyroid disease.

PMID- 9018920
TI  - Clinical aspects and diagnosis of thyroid hormone transport protein anomalies.

PMID- 9018921
TI  - Improving childhood immunizations in a family practice office.
AB  - PURPOSE: In the fall of 1993, the Family Medicine Center (FMC) of the Medical
      Center of Delaware instituted an office-based program designed to improve
      preventive care for children. This study examined whether the "Pediatric
      Prevention Program" (PPP) resulted in an improvement in childhood immunization
      rates for FMC patients. METHODS: Using chart review, we compared the percentage
      of two-year-old FMC patients who had completed appropriate immunizations before
      and after the PPP. We examined completion rates for the primary series of each
      immunization, for booster immunizations and for the combined total immunization
      series (four DPTs, three OPVs, one MMR, four HIBs). We also determined whether
      immunization rates were affected by patient demographics, pattern of office
      visits, and physician level of experience. RESULTS: After implementation of the
      program, the percentage of 2-year-old children who had completed the appropriate
      immunizations increased for all types of immunizations. The increase was greatest
      for HIBs (6 percent for the primary HIB series and 7 percent increase for the HIB
      booster) and for the combined total series (10 percent increase). Children who
      made few office visits were the least likely to have completed immunizations, but
      also saw the greatest benefit from the PPP. CONCLUSIONS: This study shows the
      positive impact of an office-based intervention for improving childhood
      immunizations. However, the improvements are relatively small and not sufficient
      to achieve optimal immunization rates throughout the community. In order to
      achieve these goals, additional interventions are needed which target high risk
      children, especially those who change physicians or who visit their physician
      infrequently. Targeting such children will likely require better data systems to
      track immunizations both in the office and across the community. These efforts
      should be given a high priority in Delaware.

PMID- 9018922
TI  - Health care information and class in America.

PMID- 9018923
TI  - Infectious waste generator annual reports.

PMID- 9018924
TI  - Management of hyperlipidaemia.

PMID- 9018925
TI  - Long-acting progestogen-only contraception.

PMID- 9018926
TI  - Flourishing otomycosis.

PMID- 9018927
TI  - Self-"treatment" for laryngeal papillomatosis.

PMID- 9018928
TI  - An unusual appearance of velopharyngeal closure in a post
      uvulopalatopharyngoplasty patient.

PMID- 9018929
TI  - Single intradermal skin tests.

PMID- 9018930
TI  - Ablation of posterior semicircular canal for benign paroxysmal positional
      vertigo.
AB  - Obstruction of the posterior semicircular canal to prevent fluid movement without
      injury to the neurosensory end organ has been shown to be effective treatment for
      benign paroxysmal positional vertigo. Risk of injury to the inner ear with loss
      of hearing has been reported with a variety of techniques. This paper will
      describe a modification of the procedure to ablate the posterior semicircular
      canal and to minimize the risk of inner ear injury. The procedure has been
      performed on 17 patients with prompt and lasting relief of vertigo and no hearing
      loss. The procedure seems to be a valuable and effective treatment for the
      disturbing condition of benign paroxysmal positional vertigo.

PMID- 9018931
TI  - Replacement of a single-channel with a multichannel cochlear implant as an
      upgrade.
AB  - The removal of a functioning cochlear implant in order to upgrade to a more
      advanced device is a critical issue to many otologists, since we currently have
      no means to predict the results preoperatively. This paper reports on two
      patients who successfully upgraded from a single-channel to a multichannel
      implant. The new implants outperformed the original devices in both the live
      voice test and the videotaped test. The patients stated that the hearing quality
      afforded by the multichannel implant was much better than that provided by the
      original implant.

PMID- 9018932
TI  - Immunologic evaluation of the child with recurrent otitis media.

PMID- 9018933
TI  - Mantle cell lymphoma appearing as a tongue base mass.

PMID- 9018934
TI  - A multifactorial analysis of facial nerve results in surgery for cerebellopontine
      angle tumors.
AB  - Preserving the function of the facial nerve remains a paramount objective in
      acoustic neuroma surgery. This study was undertaken to determine the influence of
      four independent variables on facial nerve outcome by means of a retrospective
      review of 111 surgical cases: 1) tumor size; 2) use of intraoperative facial
      nerve monitoring (IFNM); 3) completeness of tumor resection; and 4) surgical
      approach used. Partial tumor resection appeared to result in improved facial
      nerve outcome for patients with large tumors. Results indicated that tumor size
      did not correlate with facial nerve functional outcome, with no statistically
      significant differences observed among the three size categories. Facial nerve
      function was not found to depend on selection of either a translabyrinthine (n =
      47) or a suboccipital (n = 55) surgical approach in that results were similar for
      both groups. Outcome data showed a trend in support of the use of IFNM,
      especially for large tumors, even though the differences between monitored and
      unmonitored groups were not statistically significant. This study describes the
      independent impact of the four factors generally thought to affect facial nerve
      outcome and, in addition, recommends the use of data stratification in reporting
      facial nerve function results.

PMID- 9018935
TI  - Primary nasopharyngeal tuberculosis: case report and review of the literature.

PMID- 9018936
TI  - Persistent trigeminal artery as a cause of dizziness.
AB  - Complaints of vertigo and dizziness are common problems referred to
      otolaryngologists for evaluation. Awareness of uncommon causes of dizziness
      increases the physician's ability to diagnose and treat these patients. We
      present the case of a middle-aged woman who presented with episodes of vertigo
      and symptoms suggestive of vertebrobasilar insufficiency. These symptoms were the
      result of a persistent trigeminal artery (PTA) and occlusive carotid artery
      disease. A PTA is a carotid-basilar anastomosis that has been reported to be
      demonstrated on 0.1% to 0.6% of all cerebral angiograms. Persistence of this
      vessel usually leads to hypoplasia or agenesis of the ipsilateral posterior
      communicating artery, and leaves the internal carotid artery as the main source
      of blood supply to the region of the upper brainstem. The appearance and clinical
      significance of this unusual condition will be discussed.

PMID- 9018938
TI  - Treating TMJ.

PMID- 9018937
TI  - Coning candles--an alert for otolaryngologists?

PMID- 9018939
TI  - The struggle over public opinion.

PMID- 9018940
TI  - Insolvency risk in health carriers: innovation, competition, and public
      protection.
AB  - This paper reviews the framework of regulatory and managerial devices that have
      evolved in response to the special dangers to the public posed by insolvency of
      health carriers. These devices include "prudential" measures designed to decrease
      the likelihood of insolvency, and measures to "protect enrollees" in the event
      that insolvency occurs nevertheless. It also reviews the current debate over how
      this framework should be adapted to new forms of risk-bearing entities,
      especially provider-sponsored networks engaged in direct contracting with
      purchasers of coverage. Parallels to solvency concerns in the banking industry
      are explored.

PMID- 9018941
TI  - Trust and trustworthy care in the managed care era.
AB  - Trust is essential to the doctor/patient relationship, but trust in physicians'
      fiduciary ethic has become less plausible as a protector of patients' interests.
      The rise of managed care often is seen as undermining the fiduciary ethic and
      lessening the trustworthiness of care. But can managed care enhance that
      trustworthiness? Four possible sources of trustworthiness in managed care are
      discussed: ethical standards in the managed care industry, nonprofit
      organizations, physician control, and performance monitoring by purchasers.
      Limitations on all of these fronts suggest the continuing importance of a strong
      fiduciary ethic on the part of physicians who make patient care decisions.

PMID- 9018942
TI  - Measures of trust in health care.

PMID- 9018943
TI  - Professional standards in health care: calling all parties to account.

PMID- 9018944
TI  - Physician staffing ratios in staff-model HMOs: a cautionary tale.
AB  - Predictions of imminent large physician surpluses stem from two observations:
      rapid increases in the proportion of Americans in managed care plans, and the
      relatively lean physician staffing ratios reported for health maintenance
      organizations (HMOs). We use internal data from two large, mature staff-model
      HMOs to determine precise specialty-specific physician staffing ratios, to see
      whether these HMOs use fewer physicians than the fee-for-service sector uses. The
      two HMOs provided the equivalent of 180 physicians per 100,000 enrollees, which
      is near the national average and far above figures that typically are reported in
      the literature. Thus, caution regarding current workforce predictions is
      warranted.

PMID- 9018945
TI  - Physician supply and access to care in urban communities.
AB  - This paper uses an analysis of survey data from urban Californians to determine
      whether patients' reports of access to care were associated with physician
      supply. On unadjusted analyses, higher levels of physician supply were associated
      with better access to care. However, this association was no longer apparent
      after adjusting for underlying population characteristics such as insurance
      status, income, and race/ethnicity. Poorer access to care in communities with
      lower physician supply appeared to be explained mainly by lack of health
      insurance and other population characteristics rather than by physician supply.
      We conclude that a more geographically equitable distribution of physicians in
      urban areas is unlikely to compensate for an inegalitarian system of health
      insurance.

PMID- 9018946
TI  - Iconoclasm and physician workforce research.

PMID- 9018947
TI  - Civil rights in a changing health care system.
AB  - Title VI of the 1964 Civil Rights Act prohibits discriminatory conduct by
      recipients of federal financial assistance. The law has been used in the past to
      challenge discrimination in health care. The evolution of the health care system
      from fee-for-service to managed care holds much promise for minority persons, who
      historically have faced serious, extensively documented barriers to health care
      access. However, managed care providers, like their fee-for-service counterparts,
      may perpetuate past discriminatory practices in new ways. Understanding new forms
      of discrimination is important at this stage of the development of managed care,
      when program design and policy action can most effectively prevent the occurrence
      of such practices.

PMID- 9018948
TI  - Medical professionalism under managed care: the pros and cons of utilization
      review.
AB  - We contend that the full consequences of managed care for American medicine and
      health care professionals can be more fully understood if strategies for managing
      care are identified-in particular, strategies for the administrative oversight of
      professional decision making. In this paper we apply this perspective to the
      study of third-party utilization review, making use of a national survey of firms
      contracting to provide prior authorization for hospitalization in 1992. Survey
      data suggest that (1) existing approaches to utilization review differ greatly
      among review firms; (2) review practices that might improve agency and
      accountability seem to be overlooked by most review firms; and (3) a large number
      of review firms employ practices that undermine professional autonomy in
      seemingly inappropriate ways.

PMID- 9018949
TI  - The new dominance of managed care: insurance trends in the 1990s.

PMID- 9018950
TI  - Does the sale of nonprofit hospitals threaten health care for the poor?

PMID- 9018951
TI  - Tracking the demise of state hospital rate setting.
AB  - From its once preeminent position in state health policy, prospective hospital
      rate setting has declined in use from more than thirty states in 1980 to two
      today. This essay tracks the trend toward deregulation in various states-
      especially Massachusetts, New Jersey, and New York-- and examines the
      continuation of rate setting in Maryland. Principally, the decline reflects the
      development of managed care and capitation as alternative means to control health
      spending growth. This trend represents both an evolution in prospective payment
      methodology and a renewed preference for private over public-sector price
      controls.

PMID- 9018952
TI  - Association leaders speak out on health system change.

PMID- 9018953
TI  - Consumer protection in managed care: finding the balance.

PMID- 9018954
TI  - Children's access to mental health care: does insurance matter?
AB  - Using data from a 1992 community survey of children and their parents (or
      guardians), we found major gaps in mental health insurance coverage.
      Interestingly, private insurance had no statistically significant effect on use
      of mental health services. Youth without insurance coverage and those with public
      insurance had higher rates of serious emotional disorder than did those with
      private insurance. The analysis is based on the National Institute of Mental
      Health's Methods for the Epidemiology of Child and Adolescent Mental Disorders
      (MECA) study, conducted in three mainland U.S. sites and in Puerto Rico.

PMID- 9018955
TI  - Medicare beneficiaries covered by Medicaid buy-in agreements.
AB  - About 13 percent of Medicare beneficiaries receive some assistance from Medicaid.
      States "buy in" Medicare coverage for these low-income beneficiaries. For those
      eligible, states also provide benefits beyond those covered by Medicare. Buy-in
      beneficiaries are different from other Medicare beneficiaries in many ways. They
      have lower incomes, which is consistent with the policy intent. They use more
      health services in general but do not appear to receive timely, appropriate care
      relative to several disease-specific standards. As policymakers consider
      restructuring Medicare and Medicaid, careful attention needs to be paid to the
      effects of changes on these beneficiaries.

PMID- 9018956
TI  - Did Medicaid expansions for pregnant women crowd out private coverage?

PMID- 9018957
TI  - Medicaid and private insurance: evidence and implications.

PMID- 9018958
TI  - Finding practical solutions to 'crowding out".

PMID- 9018959
TI  - Crowding out: how big a problem?

PMID- 9018960
TI  - State health policy information: what worked?

PMID- 9018961
TI  - Racial segregation and ambulatory care-sensitive admissions.

PMID- 9018962
TI  - The role of payment policy in Medicare managed care growth.

PMID- 9018963
TI  - A defense of alternate-site care.

PMID- 9018964
TI  - Battle against maternal-fetal HIV transmission gaining ground in US.

PMID- 9018965
TI  - Immune correlates of protection from HIV infection and AIDS.

PMID- 9018966
TI  - MHC and behavior.

PMID- 9018967
TI  - Novel approaches to immunotherapy using thymic peptides.

PMID- 9018968
TI  - The discovery of MHC restriction.

PMID- 9018969
TI  - Why do superantigens care about peptides?

PMID- 9018970
TI  - Sentinel function of broadly reactive human gamma delta T cells.

PMID- 9018971
TI  - Immunological tolerance in germinal centres.

PMID- 9018972
TI  - Cytokines, tumour-cell death and immunogenicity: a question of choice.

PMID- 9018973
TI  - Molecular mechanisms governing reading frame choice of immunoglobulin diversity
      genes.

PMID- 9018974
TI  - Mitochondrial control of apoptosis.

PMID- 9018975
TI  - Surgery of the mitral valve.

PMID- 9018976
TI  - Pneumocystis carinii pneumonia in human immunodeficiency virus infected patients
      in Bombay: diagnosed by bronchoalveolar lavage cytology and transbronchial lung
      biopsy.
AB  - We report Pneumocystis carinii pneumonia (PCP) diagnosed by bronchoalveolar
      lavage cytology and transbronchial lung biopsy in three out of five human
      immunodeficiency virus (HIV) positive adult patients presenting with interstitial
      pneumonitis. One of these patients was serologically positive for HIV at the time
      of presentation and the remaining two patients were detected to be HIV positive
      on follow up after the diagnosis had been established. All the three patients
      were treated with co-trimoxazole. One patient recovered and was discharged;
      another patient improved with treatment but died after jugular vein cannulation
      and the third patient succumbed to cryptosporidial diarrhoea. The remaining two
      patients with non-specific interstitial pneumonitis treated with prednisolone and
      bronchodilators were recovered and were discharged from the hospital.

PMID- 9018977
TI  - Primary mediastinal tumours in the southern region of Saudi Arabia.
AB  - A retrospective review of 16 patients operated upon for primary mediastinal
      tumours was carried out. Anterior mediastinal tumours seen included retrosternal
      goitre (2), benign cystic teratoma (1), benign thymoma (1), malignant thymoma,
      spindle cell type (1) and Hodgkin's lymphoma, nodular sclerosing type (1). Mid
      mediastinal tumours included bronchial cyst (1), mediastinal granuloma (1), and
      pulmonary arterio-venous fistula (1). Neurilemmoma (2), neuroblastoma (1),
      ganglioneuroma (1), Askin tumour (1), neurofibroma (1) and benign histiocytoma
      (1) constituted the tumours of the posterior mediastinum. The tumours were
      successfully resected with minimal operative morbidity and no mortality.

PMID- 9018978
TI  - Fibreoptic assessment of post intubation laryngotracheal injuries.
AB  - The use of endotracheal intubation for respiratory support of critically ill
      patients has become a standard life saving form of therapy. Most complications of
      intubation become apparent only after extubation which may manifest in the early
      or late post extubation period. This study was undertaken to demonstrate the
      occurrence and extent of laryngotracheal injuries in intubated patients by
      performing flexible fibreoptic bronchoscopy at varying intervals following
      extubation. It was found that initial laryngoscopy findings were more pronounced
      in patients intubated for upto twelve days. Furthermore, it was also observed
      that the initial laryngeal pathology seen on fibreoptic laryngoscopy was not an
      accurate predictor for the development of adverse post extubation sequelae.
      Maxillary sinusitis developed significantly in patients intubated nasally.
      Routine flexible fibreoptic examination of the larynx following extubation is
      recommended for early detection of granulomas, synechia of vocal cords and vocal
      cord immobility to prevent troublesome sequelae.

PMID- 9018979
TI  - A diagnostic dilemma: pulmonary blastoma.

PMID- 9018980
TI  - Pneumocystis carinii pneumonia simulating as pulmonary tuberculosis in AIDS.

PMID- 9018981
TI  - Poland's syndrome with meningomyelocele.

PMID- 9018982
TI  - Rarity of "yellow nail syndrome": real or apparent?

PMID- 9018983
TI  - Empyema thoracis--a series of 230 cases.
AB  - A retrospective analysis of 230 cases of empyema thoracis which occurred in our
      clinic during the last 14 years have been presented. The causes, the pathogen
      organism, treatment with antibiotic are enumerated. The surgical treatment
      carried in resistant cases have been described Ten patients (4.34 percent) died
      due to respiratory failure and septic shock. Importance of early and appropriate
      treatment has been stressed.

PMID- 9018984
TI  - Blunt trauma abdomen: a study of 63 cases.
AB  - 63 cases of blunt abdominal trauma were studied. It was more common in males and
      in the age group 21-30 years. Majority of the injuries were due to automobile
      accidents. Commonly presenting feature was pain abdomen and vomiting. Abdominal
      paracentesis revealed haemoperitoneum in 40 cases which was subsequently
      confirmed on laparotomy in all the cases. 40 cases had no visible external injury
      but subsequent laparotomy revealed internal visceral injury in 29 cases.
      Exploratory laparotomy was carried out in 43 cases, remaining were treated
      conservatively. Liver was found to be the commonest organ injured. Post operative
      complications developed in 5 cases and deaths occurred in 7 cases mainly due to
      associated extra-abdominal injuries, poor pre-operative general condition,
      delayed diagnosis and management. We conclude that a multipronged approach
      towards early diagnosis and vigorous management should be adopted to reduce the
      morbidity and mortality in patients with blunt abdominal trauma.

PMID- 9018985
TI  - Prevalence of multi-drug resistant Salmonella typhi in Ludhiana Punjab.
AB  - A total of 945 strains of S. typhi isolated from blood cultures during 1989 to
      1994 were studied. Their antibiotic susceptibility showed 580 (61.4%) of strains
      to be multidrug resistant. The 464 strains tested for their susceptibility to
      ciprofloxacin were all sensitive to the drug. Twenty three (17.9%) of the 128
      strains of S. paratyphi A were resistant to chloramphenicol. The sole isolate of
      S. paratyphi B was sensitive to all antibiotics tested.

PMID- 9018986
TI  - Comparative values of CSF-cholesterol and CSF-triglycerides along with other
      biochemical parameters in neurological disorders.
AB  - Different parameters in CSF which are routinely investigated for the diagnosis
      and prognosis of neurological disorders do not provide confirmation to the type
      of neurological disorder. The rise in protein level in CSF was found to be
      nonspecific and estimation of glucose and chloride in CSF has lost its
      significance. Therefore, determination of concentration of CSF cholesterol and
      triglycerides may aid in the diagnosis of tuberculous meningitis, pyogenic
      meningitis, viral encephalitis and hydrocephalus. The mechanism by which the
      levels of CSF cholesterol end triglycerides are altered in neurological disorders
      is not known. The rise cholesterol and triglycerides levels in CSF may be due to
      increased activity of brain cells or by altered function of blood brain barrier.

PMID- 9018987
TI  - Allergy to tartrazine in alprazolam.
AB  - Allergy to tartrazine-containing psychotropic medication (especially
      antidepressants) had been reported. 20 patients of apparent allergy to tartrazine
      containing alprazolam brands in 480 patients exposed to the dye are described.
      Rechallenge with non tartrazine-containing alprazolam brands did not produce the
      similar allergic reactions.

PMID- 9018988
TI  - A case of paraplegia in a treated case of ca-cervix with lymphoma as a second
      malignancy--a case report.

PMID- 9018989
TI  - Self sustainability in eye care.

PMID- 9018990
TI  - Pneumatic retinopexy: principles and practice.
AB  - Pneumatic retinopexy (PR) is an alternative to scleral buckling for the surgical
      repair of selected retinal detachments. A gas bubble is injected into the
      vitreous cavity, and the patient is positioned so that the bubble closes the
      retinal break (s), allowing absorption of the subretinal fluid. Cryotherapy or
      laser photocoagulation is applied around the retinal break(s) to form a permanent
      seal. The procedure can be done in an outpatient setting, and no incisions are
      required. A multicenter randomized controlled clinical trial has demonstrated
      that the anatomic success rate is comparable to scleral buckling, but the
      morbidity is significantly less with PR. If the macula was detached for less than
      two weeks, the visual results are significantly better with PR than with scleral
      buckling. Cataract surgery was required significantly more often following
      scleral buckling than following PR. Two independent reports have shown that an
      attempt with PR does not disadvantage the eye; such that the results of scleral
      buckling after failed PR are not significantly different than primary scleral
      buckling. A comprehensive review of the world literature on PR revealed 27
      statistical series totaling 1,274 eyes. These combined series had a single
      operation success rate of 80%, and 98% were cured with reoperations. Pneumatic
      retinopexy should be considered in cases without inferior or extensive retinal
      breaks and without significant proliferative vitreoretinopathy. The cost of
      buckling varies from 4 to 10 times that of PR.

PMID- 9018991
TI  - Risk factors influencing the treatment outcome in diabetic macular oedema.
AB  - A multivariate analysis was done on 96 eyes to evaluate the effect of various
      risk factors on the final visual outcome after laser photocoagulation for
      clinically significant macular oedema (CSME) in diabetic retinopathy. Advanced
      age of the patient, large size of CSME and poor baseline visual acuity were found
      to be significantly associated with poorer outcome (p < 0.05). The association of
      nephropathy and hypertension with poorer visual outcome was of boderline
      significance (p = 0.054 and 0.07, respectively). Wavelength of the laser (argon
      or krypton) used for treatment did not significantly influence the outcome.

PMID- 9018992
TI  - Lens induced glaucomas--visual results and risk factors for final visual acuity.
AB  - Lens induced glaucomas are a common occurrence in India. An attempt was made to
      understand the clinical modes of presentation and post operative visual results
      in 93 patients with lens induced glaucoma, 49 phacomorphic and 44 phacolytic,
      attending our institute during 1994. All these patients were subjected to a
      planned extracapsular cataract extraction. Forty four percent had a posterior
      chamber intraocular lens implantation following surgery. Fifty seven percent eyes
      with phacomorphic glaucoma and 61% with phacolytic glaucoma recovered visual
      acuity of 6/12 or better. There was no significant difference in the final visual
      acuity between those patients who had an intraocular lens implanted and those who
      did not (P = 0.18). Univariate analysis was performed for selected risk factors
      such as age, sex and duration of glaucomatous process as predictors of final
      visual acuity and odds ratios with 95% confidence intervals were calculated.
      Patients with age more than 60 years (OR = 2.7, 95% CI = 1.04-6.93) and in whom
      the glaucoma was present for more than 5 days (OR = 3.1, 95% CI = 1.21-8.13) had
      a significantly higher risk of poor visual outcome post-operatively.

PMID- 9018993
TI  - Short-term results of initial trabeculectomy with intraoperative or postoperative
      5-fluorouracil for primary glaucomas.
AB  - Thirty three eyes of 33 patients were prospectively evaluated to study the short
      term efficacy, and overall surgical outcome of initial trabeculectomy for primary
      glaucomas with adjunctive intraoperative on postoperative 5-Fluorouracil (5-FU)
      use. Twelve eyes served as control who underwent trabeculectomy without
      adjunctive antimetabolites. Eleven eyes received intraoperative 5-FU, while 10
      eyes received subconjunctival 5-FU postoperatively. Intraocular pressure (IOP)
      was maintained below 22 mmHg at 3 months of follow up in 90.9% and 80% of
      patients in the intraoperative and postoperative 5-FU groups respectively,
      without use of additional antiglaucoma medications, whereas 66.7% of the patients
      in the control group achieved similar IOP levels. Hypotony (I.O.P. < 6 mmHg) was
      seen more commonly after intraoperative 5-FU (27.3%). Corneal epithelial defects
      were seen exclusively in the postoperative 5-FU group (40%). The use of
      intraoperative 5-FU exclusively as a mode of antimetabolite delivery seems an
      acceptable alternative to enhance success rates of trabeculectomy for the primary
      glaucomas.

PMID- 9018994
TI  - New standardized visual acuity charts in Hindi and Gujarati.
AB  - Conventional Snellen visual acuity chart has unequal difficulty score and
      irregular progression in letter size causing jumping effect at different visual
      acuity levels. There is also increase in number of letters from above downwards.
      Consequently one or two mistakes per line has different meaning of visual acuity
      at different levels. We designed a new visual acuity chart of fourteen lines in
      Hindi and Gujarati to facilitate standardization in visual acuity measurement.
      These charts are designed for use at six meter distance, and the illumination is
      provided from front. These charts provide a standardized way of measuring visual
      acuity using local languages.

PMID- 9018995
TI  - Malignant melanoma of conjunctiva with xeroderma pigmentosa--a case report.

PMID- 9018996
TI  - Glaucoma like defect on automated perimetry caused by cataract.

PMID- 9018997
TI  - An unusual case of syringocystadenoma papilliferum of the eyelid.

PMID- 9018998
TI  - Periodic alternating nystagmus treated with retrobulbar botulinum toxin and large
      horizontal muscle recession.

PMID- 9018999
TI  - Asepsis in ophthalmic operating room.

PMID- 9019000
TI  - Surgical magnification for intracapsular cataract surgery in a rural hospital.
AB  - Intracapsular cataract extraction is still the most common type of operation
      performed in India, especially in eye camps, and most of these are done without
      magnification. To assess the surgical outcome of intracapsular cataract surgery
      in a rural hospital with various magnifying systems, 121 consecutive eyes (121
      patients) with uncomplicated cataract were randomly allocated to surgery with the
      operating microscope, binocular loupe or unaided eye. The surgery was performed
      by either consultants or first year residents. The best corrected vision at least
      four weeks post-operatively was compared among the three groups. The performance
      between the consultants and the junior residents was also compared. The
      improvement of surgical outcome with magnification was statistically significant
      (p = 0.0045); and clinically important with a relative risk reduction of 60.6%.
      The comparison between microscope and loupe magnification did not show a
      significant difference (p = 0.24). However, with an operating microscope, the
      consultants performed significantly better than the junior residents. These
      findings suggest that the use of magnification in intracapsular cataract
      extraction provides a definite advantage over an unaided eye and that the
      binocular loupe is a good alternative to the operating microscope in this kind of
      surgery.

PMID- 9019001
TI  - HIV/AIDS risk in heterosexual college students. A review of a decade of
      literature.
AB  - Empirical studies dealing with the psychosocial correlates of HIV risk among
      heterosexual college students are reviewed, including findings related to such
      theoretical variables as HIV/AIDS-related knowledge, personal and partner's
      attitudes toward condom use, perceived susceptibility, communication with sex
      partners, and sexual self-efficacy. Although college students are highly
      knowledgeable about basic HIV/AIDS facts, they retain some misperceptions about
      disease transmission. They hold neutral-to-negative hedonistic and practical
      attitudes about using condoms: those who have engaged in risky behavior
      accurately perceive their greater susceptibility to infection and experience
      anxiety regarding transmission of HIV infection. Heterosexual college students
      communicate infrequently with their partners about safer sex, but they often
      agree to a partner's suggestion that they use condoms. Higher levels of sexual
      self-efficacy among college students have been associated with a lower risk for
      HIV transmission. Limitations and clinical implications of the findings and
      recommendations for future interventions are discussed.

PMID- 9019002
TI  - Coping resources and self-perceived well-being of college students who report a
      parental drinking problem.
AB  - Nine hundred eighty undergraduates from a major university completed a
      questionnaire designed to collect data on the associations between parental
      drinking and the students' coping resources and well-being. Three groups were
      identified: those with a parental alcohol problem (DP+), those with no problem
      (DP-), and those who were unsure. Discriminant analysis revealed similarities
      between the DP+ and unsure participants on the response variables. The coping
      resource scores of the DP- group were significantly higher than the scores of the
      DP+ and unsure groups. The unsure group had the lowest mean scores on the total
      coping resources inventory and on the Cognitive, Emotional, and Spiritual and
      Philosophical subscales. The DP+ group had significantly lower scores than the DP
      group on the Cognitive, Spiritual and Philosophical, and Physical scales.
      Although DP+ students' perception of well-being was significantly lower than that
      of their DP- peers, the entire sample was reasonably healthy, as measured by the
      General Well-Being Schedule.

PMID- 9019003
TI  - Cardiovascular disease risk factors in black college students.
AB  - Selected cardiovascular disease risk factors in 238 Black 1st-year college
      students (89 men and 149 women) were examined. Students responded to a health
      risk survey asking about their blood pressure and cholesterol levels as well as
      their smoking and physical activity habits. Approximately 2% of the men and 3% of
      the women reported having high blood pressure. Forty-three percent of the men and
      48% of the women had never had their cholesterol level checked or could not
      remember the result of the test. Only 6% of the men and 5% of the women reported
      that they smoked cigarettes. More women (62%) than men (38%) engaged in vigorous
      physical activity fewer than three times per week. The results indicated that
      health professionals need to increase awareness of blood cholesterol levels among
      Black men and women and should focus intervention efforts on increasing the
      physical activity levels of Blacks, especially women.

PMID- 9019004
TI  - Same-sex rape of male college students.
AB  - Rape of men by other men is a widely neglected yet increasingly recognized form
      of sexual assault. Information on same-sex rape involving men is frequently
      absent in campus rape education and prevention programming because the general
      public and popular culture have traditionally viewed rape in a context of
      violence against women. Available medical and psychological literature indicates
      the need for expanded prevention, treatment, and research dealing with men who
      rape other men. Several initiatives in the areas of curriculum infusion, support,
      services, training, and public policy for addressing same-sex rape of men in
      campus communities are offered.

PMID- 9019005
TI  - Cognitive mapping: its use as an assessment tool for client education.
AB  - To provide adequate educational interventions for students living with chronic
      illnesses, health professionals must develop methods suited to each individual's
      needs. Too often, clients are lumped into a category based on the illness
      diagnosis and few other factors are taken into consideration. Regardless of the
      diagnosis, each individual presents with authentic mental representations of the
      illness and the impact of that illness on important aspects of his or her life.
      The health professional can offer comprehensive educational interventions when
      all aspects of the client's own understanding of illness are assessed. Cognitive
      mapping is an assessment technique that can be used in addition to the initial
      interview and can be useful throughout the educational process to determine
      changes in mental representations.

PMID- 9019006
TI  - Athletic mouth guards prevent orofacial injuries.
AB  - Competitive and recreational athletes are at significant risk of orofacial
      injury. The use of mouth guards and face shields can substantially reduce that
      risk. In this article, the author summarizes the known incidence of orofacial
      trauma and the benefits of using athletic mouth guards and advises college health
      professionals to advocate mouth guards for athlete-patients who are at risk.

PMID- 9019007
TI  - In praise of alternative medicine: views of a healthcare consumer and college
      health employee.

PMID- 9019008
TI  - Peer education: a viewpoint and critique.
AB  - Peer education has been promoted by college health service health education
      programs for many years. This Viewpoint questions some assumptions that underlie
      the use of peer health educators and highlights some of the problems of training
      peers as paraprofessionals.

PMID- 9019009
TI  - Peer education: a commentary.

PMID- 9019010
TI  - Can a super oral rehydration solution stimulate intestinal repair in acute viral
      enteritis?
AB  - This study was designed to screen several treatments for their effects on mucosal
      repair in an established model of piglet rotavirus enteritis. Six ingredients
      selected to facilitate repair were added to the oral rehydration solution (ORS)
      and subsequently to the diet: L-glutamine (GLN); rice solids; a soluble fiber
      (carboxymethylcellulose); nucleotides; polyamines; and fructooligo-saccharides.
      Rotavirus infection consistently induced a watery diarrhoea lasting 5 to 10 days
      and produced a jejunal mucosal lesion which was maximal at 3 days, post
      inoculation (manifested by a reduction of villus surface area to 30% to 50% of
      normal). By 7 to 10 day post-inoculation, the villus surface area returned to 50%
      to 80% of normal. None of the supplemental ingredients added to the ORS had a
      significant effect in either shortening the clinical illness or in stimulating
      recovery of the affected mucosa. It is concluded that several types of "Super
      ORS" are ineffective in enhancing repair in viral enteritis in neonatal colostrum
      deprived piglets. These results do not rule out beneficial effects of the
      additives tested in subjects with more extensive intestinal damage, in those who
      receive breast milk, or in those with bacterial enteritis.

PMID- 9019011
TI  - Epidemiology and transmission of V. cholerae O1 and V. cholerae O139 infections
      in Delhi in 1993.
AB  - In 1993, rectal swabs from clinically suspected cases of cholera admitted to the
      Infectious Diseases Hospital (IDH), Delhi were examined for Vibrio cholerae O1
      and O139. Epidemiological data of 396 cholera cases were collected before the
      patients' discharge from IDH. Of the 1528 laboratory-confirmed cholera cases, 46%
      and 54% were caused by serotype O1 and O139 respectively. Both serotypes appeared
      and disappeared simultaneously, and peaked during the same time of the year.
      However, the two serotypes affected persons of different age groups; about 65% of
      the O1 cases occurred in children aged less than 10 years, whereas this age group
      accounted for 40% of the cases due to V. cholerae O139. Although there were some
      focal outbreaks due to serotype O139, both serotypes had almost similar
      geographical distributions. Important risk factors for transmission of cholera
      were almost equally prevalent in the majority of both types of cholera cases.
      Since the seasonality, geographical distribution, and risk factors for
      transmission were similar for both serotypes, the study indicates that the
      preventive and control measures are also likely to be similar. The study also
      shows that the emergence of V. cholerae O139 in 1993 did not affect the
      incidence, seasonality, and epidemiology of endemic V. cholerae O1 E1 Tor strains
      in Delhi.

PMID- 9019012
TI  - Changing patterns of the prevalence of different Shigella species and their
      antibiotic susceptibilities in Ankara, Turkey.
AB  - Shigella flexneri was the most common Shigella serogroup isolated in Turkey.
      Recently, an increase in the number of Shigella sonnei isolates was noticed. A
      retrospective analysis of 2,710 isolates, obtained from stools of Turkish
      children between January 1980 and September 1994, revealed that, between 1980 and
      1987, S. flexneri was the most common subgroup. The isolation rate of S. sonneri
      increased steadily from 1987 to 1994 reaching to a peak of 78% of all isolates in
      1991. The antibiotic susceptibility of 206 strains isolated in 1994 was also
      studied. A marked difference between the two species was observed for
      chloramphenicol (98% susceptibility in S. sonnei versus 20% in S. flexneri,
      ampicillin (90% vs. 18%), ampicillin-sulbactam (98% vs. 53%), and tetracycline
      (46% vs. 18%) (p < 0.001). Susceptibility to trimethoprim-sulphamethoxazole was
      similar between the two groups (42% vs. 38%). All isolates were susceptible to
      ciprofloxacin and ceftriaxone. Comparing our results with resistance rates in
      1989, a marked increase in amplicillin (from 44.1% to 82%), chloramphenicol (from
      36.7% to 56%) and trimethoprim-sulphamethoxazole (from 35.8% to 62%) resistance
      was observed.

PMID- 9019013
TI  - Plasma vitamin A, zinc and selenium concentrations in children with acute and
      persistent diarrhoea.
AB  - Plasma zinc, selenium, and vitamin A concentrations in 25 children with
      persistent diarrhoea (PD) and acute diarrhoea (AD) were determined and compared
      with 25 age-matched control children. Plasma retinol concentrations (PRC) and
      plasma zinc concentrations (PZC) (3.92 micrograms/dL and 79.4 micrograms/dL
      respectively) were found to be significantly lower (p < 0.05) in children with
      PD. PZCs were also significantly reduced (p < 0.05) in children with AD. However,
      reduction in PZC was more in PD than that in AD. There was no significant
      difference in PSC in children with either types of diarrhoea as compared with the
      control group. The results of the study showed that there was deficiency of
      vitamin A and zinc in diarrhoeas which needs to be correlated for proper
      nutritional management.

PMID- 9019014
TI  - Oscillatory fluctuations in the incidence of rotavirus infections by serotypes 1,
      2, 3, and 4.
AB  - The statistical evidence for regularity in the epidemic cycles of rotavirus
      infection for serotypes 1, 2, 3, and 4 was examined. Hospitalization longitudinal
      data of the monthly incidence of rotavirus infections from the city of Melbourne,
      Australia during 1977-1993 were used. Periodograms were used for exploring
      seasonal and longer-term cycles (interepidemic periods) of rotavirus infection.
      There was a satisfactory agreement between the interepidemic period estimated by
      means of periodograms with the one predicted by theoretical epidemiological
      studies. Thus, there is a clear evidence of a biennial peak in the epidemiology
      of rotavirus. Results of the study show an evidence of the likely existence of an
      interepidemic cycle of 4.6-5.2 years of duration. The finding of this
      interepidemic cycle was unexpected, and does not arise from the alternating
      incidence of the 4 serotypes since this peak appears in the periodogram of each
      serotype.

PMID- 9019015
TI  - Inter-relationships among subgroups, serotypes, and electropherotypes of
      rotaviruses isolated from humans.
AB  - In an epidemiological study of human rotavirus (HRV) infections in metro Jeddah,
      Saudi Arabia, the relationships among subgroups, serotypes, and RNA
      electropherotypes of the rotavirus isolates were investigated. Of the 523
      rotavirus-positive stool specimens, 245 were examined for subgroup, serotype, and
      electropherotype. Of these, 84 isolates were analyzed for their subgroup and RNA
      electropherotype specificites, 12 (14.3%) were of subgroup 1, 69 (82.1%) were of
      subgroup II, and 3 (3.6%) were a mixture of subgroup I and II. Of the subgroup 1
      specimens, 5 (41.7%) showed long electrophoretic migration patterns and 7 (58.3%)
      showed short patterns. In subgroup II specimens, 66 (95.7%) were of long patterns
      and 3 (4.3%) of short patterns. The relationship between HRVS serotypes and
      electropherotypes was also determined for the same 245 rotavirus specimens. Of
      these, 36 (14.7%) exhibited short RNA patterns and 209 (85.3%) exhibited long
      patterns. The short pattern specimens consisted of serotype 1 (8.3%), serotype 2
      (63.9%), serotype 3 and serotype 4 (2.8%) each. The long pattern specimens
      consisted of serotype 1 (60.3%), serotype 2 (1.4%), serotype 3 (7.2%) and
      serotype 4 (17.7%). Among the previous 245 specimens, subgroup specificities were
      available for 51 specimens. All subgroup I were of serotype 2, and all subgroup
      II were of serotype 1, 3 or 4. RNAs of either subgroup showed both long and short
      electropherotypes. No relationship could be established between subgroups or
      serotypes and a particular electropherotype. It seems unlikely that
      electropherotyping of human rotavirus (HRV) can be used for identifying the
      subgroups or serotypes of strains.

PMID- 9019016
TI  - Detection of enterotoxigenic Escherichia coli, Shigella and Campylobacter spp. by
      multiplex PCR assay.
AB  - Three oligonucleotide primers were used in a polymerase chain reaction (PCR)
      assay for the simultaneous amplification of regions of the invasive plasmid
      antigen (ipaH) of Shigella spp., flagellin gene (flaA) of Campylobacter spp., and
      heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC). The
      multiplex assay was performed using DNA extracted by a chaotropic method directly
      from diarrhoeal stools. The diagnostic efficacy of the assay was analyzed by
      agarose gel electrophoresis. This assay shows a novel approach for the diagnosis
      of diarrhoea caused by Shigella spp., ETEC, and Campylobacter spp.

PMID- 9019017
TI  - Cryptosporidiosis among cancer patients: an observation.
AB  - The incidence of cryptosporidiosis was studied in 560 cancer patients presenting
      with symptoms of diarrhoea. Cryptosporidium oocysts were detected in the stool
      specimens by modified acid fast staining. Blood was examined for HIV antibodies
      from patients whose stool specimens were positive for Cryptosporidium oocysts.
      Oocysts were detected in 7 of the 560 (1.3%) patients who were receiving
      chemotherapy and had diarrhoea; in five of them the symptoms were acute, while
      tow patients had chronic diarrhoea. Of these seven patients, five had cancer of
      haemopoetic system, one had cancer of cervix and one had uterine sarcoma. None of
      the patients positive for oocysts were positive for HIV antibodies, ruling out
      the possibility of an opportunistic infection due to HIV infection.

PMID- 9019018
TI  - Vibrio cholerae O139 in the subcontinent.

PMID- 9019019
TI  - Prevalence of diarrhoeagenic Escherichia coli in Kenyan children.

PMID- 9019021
TI  - Bibliography on diarrhoeal diseases.

PMID- 9019020
TI  - Evidence for possible involvement of guanylate cyclase in diarrhoea induced by
      castor oil in mice.

PMID- 9019022
TI  - How a community-academic partnership serves as a force for change in health care
      and health professions education.

PMID- 9019023
TI  - Designing a survey of public opinions regarding alcohol control policies among
      African American and white adults.

PMID- 9019024
TI  - Wisconsin's welfare reform and its potential effects on the health of children.

PMID- 9019025
TI  - Managed care and community-oriented care: conflict or complement?
AB  - Motivated by the need for fundamental change, reform of the health care delivery
      system is continuing despite the recent failure of national initiatives. One
      aspect of this reform is the restructuring of managed care systems to include low
      income, at-risk populations in their health delivery program: It is a move that
      threatens current "safety-net" providers, which already serve these populations
      with programs that combine public health and traditional primary care. This paper
      explores this potential conflict by providing a brief history and comparison of
      the main features of the community-oriented primary care (COPC) and health
      maintenance organization (HMO) models. The authors provide a frame-work that
      contrasts the structure, process, and outcome characteristics of these two
      models, delineating key similarities and differences. The frame-work is used in
      profiling a service delivery system model that integrates the two systems and in
      discussing issues related to operationalizing the proposed integration.

PMID- 9019026
TI  - Developing a medical achievement reading test to evaluate patient literacy
      skills: a preliminary study.
AB  - A medical terminology achievement reading test (MART) administered to patients
      was developed for health care practitioners and researchers. In this study, 405
      respondents from five populations (nursing home patients, college students, high
      school students, adult basic education students, and shopping mall customers)
      took both the MART and the Wide Range Achievement Test (WRAT). Cronbach's
      reliability test alpha indicated a high level (alpha = 0.98) of likelihood that
      the MART score is a good estimate of the true score (WRAT), and, therefore,
      reading ability. MART is designed to resemble a prescription label with its use
      of small print size, glossy cover, and medical terminology. This design allows
      practitioners and researchers to assess patients' inability to read the test. It
      is thought that its design and use of medical terminology makes the MART less
      threatening to patients than other literacy tests. Further studies of the MART in
      low-literate populations could determine whether this is true.

PMID- 9019027
TI  - Health status of and access to health services by residents of urban encampments
      in Los Angeles.
AB  - This paper reports findings from a survey of 134 homeless people living in 42
      urban encampments in central Los Angeles. These data, of concern to public health
      officials, include the physical conditions in the camps, the health status of
      residents, their use of drugs and alcohol, and their access to and use of health
      care services such as substance abuse treatment. Many encampment residents report
      poor health status; over 30 percent report chronic illnesses, and 40 percent
      report a substance abuse problem. Although outreach efforts have had success in
      bringing HIV and tuberculosis screening services to encampments, residents report
      significant barriers to using primary health care and drug and alcohol treatment
      services. Public hospitals and clinics remain the major source of primary medical
      care for homeless people living in encampments. Outreach and case management
      continue to be critical components of improved access to health care for homeless
      people.

PMID- 9019028
TI  - Differences in follow-up visits between African American and white Medicaid
      children hospitalized with asthma.
AB  - Asthma-related hospitalizations and mortality have risen at alarming rates in the
      past two decades, taking a disproportionate toll on African American children.
      Adverse asthma outcomes have been attributed to inadequacies in primary care,
      raising concerns about the quality of primary care delivered to African American
      children. To assess differences in care between African American and white
      children, the authors identified 500 children enrolled in Massachusetts Medicaid
      and hospitalized for asthma, and reviewed their medical claims data for the six
      month period after hospitalization. It was found that African American children
      had significantly fewer primary care visits than their white counterparts, even
      after adjusting for potential confounding variables. In contrast, emergency
      service utilization did not differ by race. The authors conclude that racial
      disparity exists in primary care access among children with asthma. Interventions
      should be designed to target poor African American children who suffer
      disproportionately from this life-threatening yet treatable disease.

PMID- 9019029
TI  - Role burdens: the impact of employment and family responsibilities on the health
      status of Latino women.
AB  - This paper explores the relative effects of employment and family responsibility
      on the perceived health status of Latino women. The data source analyzed for this
      study was the 1990 Panel Study of Income Dynamics/Latino National Political
      Survey (PSID/LNPS) Early-Release File (n = 1,502). Regression analyses were used
      to investigate the contributions of variables associated with perceived health
      status, including sociodemographics, Latino ethnicity, language, employment, and
      family responsibility. The results suggest that annual employment hours,
      occupation, and family responsibilities, such as child care and weekly housework,
      significantly affect self-reported health status of employed Latinas. Both social
      causation and social selection may be underlying the associations found. The
      results suggest that there is need for the development of public policies that
      seek to increase Latinas' labor force participation rate since any expansion has
      the potential to have a positive impact on their health status.

PMID- 9019030
TI  - On the ethics of euthanasia discourse.

PMID- 9019031
TI  - Decreased opioid doses used on a palliative care unit.
AB  - We have previously published data on our use of opioids in the last week of life.
      A change in our pattern of opioid use, i.e. switching opioids more frequently and
      using high-dose methadone suppositories, appears to have resulted in a decrease
      in the number of patients requiring high-dose opioids. A retrospective chart
      review of 100 consecutive patients treated on our palliative care unit during
      1992 was completed and compared to the original data from 1990. Results confirmed
      a decrease in the range of opioids used, as well as a statistically significant
      decrease in the daily opioid dose in the last week of life. We believe that this
      difference is most likely due to the use of methadone in patients showing either
      a poor response to other opioids or a rapid development to tolerance, as well as
      switching opioids more frequently to take advantage of incomplete cross
      tolerance.

PMID- 9019032
TI  - Family members' perceptions of palliative cancer care: predictors of family
      functioning and family members' health.
AB  - We studied family members' care experiences during the palliative care phase as
      predictors of family members' health and family functioning during the palliative
      care phase and three months following the death of the patient. Eighty family
      members of advanced cancer patients participated in the study at time one (T1)
      (palliative care phase) and 64 family members completed the data collection
      protocol at time two (T2) (three months bereavement). Data were also obtained
      from 36 of the patients within one month of their deaths. Fulfillment theory
      accounted for 31% of the variance in family care satisfaction and Discrepancy
      theory accounted for 72% of the variance in family care satisfaction. Discrepancy
      theory predicted family functioning in the bereavement period (r = -0.33, p <
      0.05). Patients' quality of life scores were moderately correlated with family
      members' health during the palliative care phase (r = -0.38, p < 0.05). Family
      members' scores on the health index (symptom of stress scale) were significantly
      lower (p < 0.05) than normative scores reported in a study using a healthy
      population. The strongest predictor of family members' health scores in the
      bereavement period was their health score at T1 (r = 0.71, p < 0.01). As well,
      family functioning at T1 was strongly correlated with family functioning at T2.

PMID- 9019033
TI  - Slow euthanasia.

PMID- 9019034
TI  - Morphine drips, terminal sedation, and slow euthanasia: definitions and facts,
      not anecdotes.

PMID- 9019035
TI  - Morphine infusions at the end of life: the pitfalls in reasoning from anecdote.

PMID- 9019036
TI  - Approaches to palliative care by primary health care teams: a survey.

PMID- 9019037
TI  - Significant morbidity associated with bone metastases in a patient with breast
      cancer.

PMID- 9019038
TI  - Revising theories on adolescent development through observations by nurses.

PMID- 9019039
TI  - Behavior changes exhibited by siblings of pediatric oncology patients: a
      comparison between maternal and sibling descriptions.
AB  - The purpose of this study was to identify the coping strategies used by the well
      siblings of pediatric oncology patients as identified by both the mother and the
      well siblings. The findings of this research study showed that both mothers and
      the well siblings were able to identify behavioral changes (95.2% of the mothers
      and 85.7% of the well siblings identified behavior changes). Behavior changes
      identified by both the siblings and mothers included being more sensitive to the
      needs of others, being more thoughtful, playing with friends, fighting, trouble
      sleeping, and complaints of headaches. Nurses can conduct thorough assessments of
      sibling behavior changes when a child family member has been diagnosed with
      cancer. From these assessments, nurses can provide care to assist the entire
      family during the ill child's treatment.

PMID- 9019040
TI  - Life situation and problems as reported by children with cancer and their
      parents.
AB  - In recent years, the intensification of treatment for children with cancer has
      resulted in a considerable increase in the number of those who are cured. The
      intensive treatment has, however, led to a number of problems for the children
      and their families. The aim of this study was to identify children's experience
      of problems related to their cancer and the disease-effect on the child's life
      situation. Five children with varying diagnoses and treatment plans and five
      parents were interviewed separately. The qualitative interview data were compared
      with a quantitative measurement of problems. The interview data were analyzed by
      two of the authors according to qualitative analysis processes. Six categories
      regarding influencing factors on the children's life situation were found: (1)
      medical treatment and side effects, (2) isolation, (3) togetherness and support,
      (4) being in the center, (5) feelings and reactions, and (6) quality of care.
      About half of the variables on the list of problems were mentioned in 1 or more
      of the 10 interviews. Study findings suggest that health care personnel help
      children with cancer to reduce their fear of painful and frightening procedures
      by creating a relationship with the child.

PMID- 9019041
TI  - Hypnosis for children and adolescents with cancer: an annotated bibliography,
      1985-1995.
AB  - This annotated bibliography reviews the professional literature published in
      English, from 1985 to 1995 inclusive, on the subject of the use of hypnosis with
      pediatric cancer patients. Books, chapters, and journal articles are included;
      dissertation, theses, and unpublished material are not. This bibliography
      contains 37 items organized into three categories: (1) General Discussions; (2)
      Case Reports or Case Studies: and (3) Experimental and Nonexperimental Group
      Designs. The brief annotations provided are not intended to be reviews or to be
      evaluative, but, rather, to inform the reader about the content and focus of the
      publication. This is an update of a previously published annotated bibliography,
      also presented in this Journal, which explored the relationship between hypnosis
      and pediatric cancer in journal articles published from 1960 to 1985.

PMID- 9019042
TI  - Conscious sedation of pediatric oncology patients for painful procedures:
      development and implementation of a clinical practice protocol.
AB  - Pain during treatment procedures is often identified as the most distressing
      aspect of the entire cancer experience for a child with cancer. The use of
      conscious sedation may reduce this procedure-related pain and distress. A
      clinical practice protocol is necessary to maximize the efficacy and safety of
      conscious sedation use. In this article, the processes of developing and
      implementing a conscious sedation protocol for pediatric oncology patients
      undergoing painful procedures are presented. The protocol itself is included. A
      review of the literature on conscious sedation is presented, and implications for
      pediatric oncology nursing practice are discussed.

PMID- 9019043
TI  - Challenges of clinical research for the guest investigator in the institution.

PMID- 9019044
TI  - Correlates of psychological distress among mothers of children and adolescents
      with hemophilia and HIV infection.
AB  - Evaluated the correlates of mood state (psychological distress) in a multisite
      study of two groups: (a) mothers of HIV-positive children and adolescents with
      hemophilia (n = 91), and (b) mothers of HIV-negative children and adolescents
      with hemophilia (n = 92). Socioeconomic status, quality of family relationship
      support, and frequency of negative life events accounted for significant variance
      in Total Mood Disturbance (psychological distress) as measured by the Profile of
      Mood States in the overall sample. Severity of hemophilia was unrelated to
      distress. A significant interaction between HIV status and frequency of stressful
      life events indicated that this variable related more strongly to distress among
      mothers of HIV-infected children and adolescents with hemophilia than among
      mothers of HIV-negative children with hemophilia. Findings suggest that the
      presence of HIV infection in their children and adolescents may heighten the
      impact of negative life events on the psychological distress experienced by these
      mothers.

PMID- 9019045
TI  - Controlling for general and disease-specific effects in child and family
      adjustment to chronic childhood illness.
AB  - Investigated the differential associations of asthma and diabetes on children's
      self-competence, family functioning, and maternal coping. Interactions of gender
      with the presence of chronic childhood illness were also assessed. Seventy-two
      children with diabetes and 40 children with asthma participated as subjects.
      Mothers completed measures of family functioning, coping, and disease severity
      while children completed Harter's (1985) Self-Perception Profile for Children.
      Results indicated that gender and type of chronic illness were independently
      associated with children's self-competence and family functioning but not
      maternal coping. However, differences attributable to specific illnesses
      dissipated once general family factors and general chronic childhood illness
      variables were controlled statistically. Differences based on child gender
      remained robust. Results are discussed within the context of categorical and
      noncategorical approaches to the study of chronic childhood illness.

PMID- 9019046
TI  - Body image and psychosocial adjustment in adolescent cancer survivors.
AB  - Examined body image and social adjustment in 21 adolescents who had completed
      cancer treatment and a healthy comparison group. Subjects completed
      questionnaires assessing body image and social adjustment and were videotaped
      during an interview. Raters blind to health status independently rated subjects'
      attractiveness. Cancer survivors reported less than half as many social
      activities as the healthy controls. No group differences were found on social
      anxiety, loneliness, or composite body image scores. However, within the cancer
      group, adolescents who had been off treatment longer reported lower self-worth,
      more social anxiety, and more negative body image perceptions, but were not rated
      as less attractive by observers. Findings suggest body image concerns and social
      anxiety may not develop until several years after treatment termination.

PMID- 9019047
TI  - Variables associated with anticipatory nausea and vomiting in pediatric cancer
      patients receiving ondansetron antiemetic therapy.
AB  - Investigated the prevalence of anticipatory nausea and vomiting (ANV) among 59
      pediatric cancer patients who had routinely received ondansetron (Zofran)
      antiemetic therapy and determined patient- and treatment-related factors
      associated with ANV. Of the sample, 59% indicated at least mild ANV symptoms,
      suggesting that a significant number of patients report ANV and are bothered by
      it, despite the use of Zofran. These children were compared to those reporting no
      ANV symptoms. Most ANV symptomatology was consistent with a traditional classical
      conditioning model although cognitive processes may also play a role. Children
      with greater expectations of severe postchemotherapy vomiting and those who were
      more distressed by nausea and vomiting were more likely to experience ANV
      symptoms. Implications for psychological and pharmacological treatments of ANV
      are discussed.

PMID- 9019048
TI  - Psychological aspects of childhood obesity: a controlled study in a clinical and
      nonclinical sample.
AB  - Explored the relationship between obesity and psychosocial adjustment in a
      combined clinical and nonclinical sample of 139 obese children and 150 non-obese
      children (ages from 9 to 12 years and matched for age, socioeconomic status, and
      gender) who filled out the Perceived Competence Scale for Children; their parents
      completed the Child Behavior Checklist. All obese children, independent of their
      help-seeking status, reported more negative physical self-perceptions than their
      nonobese peers and they scored lower on general self-worth. According to their
      parents, the obese children of the clinical sample appeared to have more behavior
      problems. Findings suggest that psychopathology depends on a clinical obese
      status, and they provide evidence for a psychosocial at-risk profile for a
      subgroup of obese children.

PMID- 9019049
TI  - The Child-Adult Medical Procedure Interaction Scale-Revised: an assessment of
      validity.
AB  - Investigated the validity of the Child-Adult Medical Procedure Interaction Scale
      Revised (CAMPIS-R) using multiple concurrent objective and subjective measures of
      child distress, approach-avoidance behavior, fear, pain, child cooperation, and
      parents' perceived ability to help their preschool children during routine
      immunizations. Parents', staffs', and children's behaviors in the treatment room
      were videotaped and coded. Results indicate that the validity of the CAMPIS-R
      codes of Child Coping and Distress, Parent Distress Promoting and Coping
      Promoting, and Staff Distress Promoting and Coping Promoting behavior were
      supported, with all significant correlations being in the predicted direction. An
      unanticipated finding was that the child, parent, and staff Neutral behaviors
      were inversely related to some measures of distress and positively related to
      some measures of coping. Interobserver reliability was high for each CAMPIS-R
      code.

PMID- 9019050
TI  - Patterns and correlates of supervision in child pedestrian injury. The Kids 'N'
      Cars Research Team.
AB  - Described supervision in 142 child pedestrian injuries (PI), based on presence
      and proximity of supervisors and/or peers. Children (5-12 years), families,
      sites, and PI events were described via record reviews, interviews,
      questionnaires, and site investigation. Supervision of PI victims varied with
      family size and cohesion, and with children's age, self-help skills, nearness to
      home, and activity (playing or journey). Peer presence was associated with more
      impulsive behavior among supervised (but not among unsupervised) PI victims.
      Definitions of supervision parameters offered here can aid research on the
      complex relationship between supervision and PI risk.

PMID- 9019051
TI  - Brief report: HIV-exposed newborns show inferior orienting and abnormal reflexes
      on the Brazelton Scale.
AB  - Assessed 48 infants of HIV-positive and HIV-negative mothers on the Brazelton
      Neonatal Behavioral Assessment Scale. Infants exposed to HIV-positive mothers
      were disadvantaged from birth due to their mothers having obstetric complications
      and to the infants having orienting problems and abnormal reflexes on the
      Brazelton Newborn Scale. These problems may be early precursors of the later
      visual-spatial delays and hypertonicity noted in these infants.

PMID- 9019053
TI  - Medicaid abuse in Florida: are physicians to blame?

PMID- 9019052
TI  - Brief report: preschoolers' social preferences for interacting with peers with
      physical differences.
AB  - Investigated preschoolers' playmate preferences for line drawings of a physically
      normal child, one with a facial scar, one wearing a leg brace, and one sitting in
      a wheelchair for several contexts: classroom, eating, reading, television, and
      playground. Difference in preferences for age, gender, ethnic group, and context
      were investigated. No gender differences were found. African American children
      were more accepting of a child seated in a wheelchair than Caucasian children.
      Very young children had limited understanding of the impairments. Also, the
      children were less likely to express preferences for the children with orthopedic
      impairments for the playground context. Interventions involving typically
      developing children and peers with impairments in play that does not require
      motor activity may enhance the acceptance of children with orthopedic
      impairments.

PMID- 9019054
TI  - The world is not coming to an end--quite yet!

PMID- 9019055
TI  - Narcotic prescription for pain management in Florida: the physician and the law.

PMID- 9019056
TI  - The controversy of physician-assisted suicide.

PMID- 9019057
TI  - Adequate pain treatment: a challenge for medical regulatory boards.

PMID- 9019058
TI  - Pain and symptom management in cancer patients.

PMID- 9019059
TI  - New concepts in postoperative pain management: is there more beyond pain control?

PMID- 9019060
TI  - Pain management for the AIDS patient.
AB  - The relief of pain in persons with HIV disease, while similar to other patient
      populations such as cancer patients, has some unique aspects. Pain must be a
      focus, and a priority, of care in persons with HIV disease along with treatment
      of the underlying HIV infection and the complications of immune compromise. Pain
      in patients with AIDS is very prevalent and often undertreated. Pain contributes
      to psychological and functional morbidity in AIDS. At the present time, the
      guidelines developed for treatment of cancer pain are used in patients with HIV
      disease, with the recognition that neuropathic pain should be treated differently
      from nociceptive pain. A multidisciplinary approach to pain management is
      optimal; however, consultations with pain specialists are adequate for management
      of pain in most patients, including those with HIV disease. Approaches to
      management of pain in patients with HIV disease are: Localize and characterize
      pain Work up possible etiologies Rule out infections and malignancies Be aware of
      multiple etiologies Explore the psychological/emotional contribution to pain
      Perform a thorough history and physical examination including medication history,
      history of substance use/abuse, and neurological and psychological assessments
      Treat the medical and psychological causes of pain Use appropriate pain
      medications in adequate doses Consult specialists in pain management, when
      necessary.

PMID- 9019061
TI  - Psychiatric aspects of cancer pain.

PMID- 9019062
TI  - Opioids for chronic non-malignant pain.
AB  - In summary, opioid use for chronic non-malignant pain is justified in a select
      group of patients who do not respond to a variety of other pain treatment
      modalities. Proper trials of the analgesics given "by the clock" in appropriate
      dosages with attention to potential side effects and proper documentation is
      important. Efficacy should be monitored by improvement in function and
      symptomatology. Undertreatment for fear of addiction or legal consequences should
      be avoided. Specialized pain clinics may be utilized for consultation regarding
      the long-term use of opioids or for more advanced pain management strategies,
      possibly including the use of intraspinal opioid delivery systems.

PMID- 9019063
TI  - "In a pure and holy way": personal and professional conduct in the Hippocratic
      Oath?

PMID- 9019064
TI  - Hippocratic ideals, medical ethics, and the practice of medicine in the early
      Middle Ages: the legacy of the Hippocratic Oath.

PMID- 9019065
TI  - Receptions of the Hippocratic Oath in the Renaissance: the prohibition of
      abortion as a case study in reception.

PMID- 9019067
TI  - Torture, ethics and health professionals.

PMID- 9019066
TI  - The Hippocratic Oath and modern medicine.

PMID- 9019068
TI  - It is time to react.

PMID- 9019069
TI  - Medical profession and torture.

PMID- 9019070
TI  - Torture and medical profession--an overview.

PMID- 9019071
TI  - Medical ethics and torture--Indian perspective.

PMID- 9019072
TI  - Achievement after more than 20 years of healthy professionals' work against
      government sanctioned torture.

PMID- 9019073
TI  - Community mental health and torture survivors.

PMID- 9019074
TI  - Role of medical journals in torture.

PMID- 9019075
TI  - A new epidemic.

PMID- 9019076
TI  - HLA phenotype frequencies in pulmonary tuberculosis.
AB  - Susceptibility and/or immune response to tuberculosis may or may not be
      associated with particular histocompatibility leucocyte antigen (HLA) phenotype
      frequencies. The present study was undertaken to north eastern Indian population
      to verify any association between HLA phenotypes and immune response to
      mycobacterial antigen. HLA-typing was done in 60 well Tarasaki trays and T-cell
      subsets in each group were measured using Ficoll-hypaque nylon wool columns and
      dynabeads (M-450). No universal association with particular HLA-type and
      pulmonary tuberculosis has been confirmed.

PMID- 9019077
TI  - Detection of HIV infection in pulmonary tuberculosis patients.
AB  - Well documented 112 pulmonary tuberculosis patients were studied for the
      prevalence of human immunodeficiency virus (HIV) seropositivity by using two
      antibody screening tests along with western blot test. Nineteen of the pulmonary
      tuberculosis patients were HIV seropositive, 12 were acid-fast bacillus smear
      positive; 12 patients were tuberculin skin test positive and 15 patients were
      culture positive. As the incidence of HIV infection is increasing in India, it is
      observed that patients co-infected with HIV and TB are also on the rise.
      Recognition of the dual infection and taking adequate steps to deal with this
      epidemic are needed.

PMID- 9019078
TI  - Prevalence of tuberculosis in Kishtwar Tehsil of Jammu region in Jammu and
      Kashmir State.
AB  - A study of prevalence of tuberculosis in Kishtwar tehsil of Jammu region was
      conducted from June 1991 to May 1992. A total of one thousand two hundred ninety
      eight rural as well as urban population suffering from various types of lung
      diseases was studied for prevalence of tuberculosis and a sizeable number (98) of
      patients were found to be positive of various types of tuberculosis, viz,
      pulmonary tuberculosis, tuberculous pleural effusion and miliary tuberculosis. Of
      the population studied 7.55% were found to be positive for tuberculosis and among
      them 88.76% patients were anaemic and the commonest type of anaemia was
      normocytic normochromic and normocytic hypochromic. The ESR was raised in almost
      of all the patients. Of the population, 80.61% were seen to be positive on
      skiagram chest and 58.16% were found to be positive on other diagnostic tests
      like Mantoux's tests, sputum for acid-fast bacilli, etc. Mantoux's test was
      positive in 27.55% cases and sputum was positive in 30.61% cases. All the cases
      studied were subjected to special investigations. The changes in parameters are
      consistent with the diagnosis of tuberculosis. Large family size, poverty,
      excessive smoking, illiteracy, etc, are the major contributing factors.

PMID- 9019079
TI  - Effectiveness of bacillus of Calmette-Guerin (BCG) vaccination against
      tuberculous meningitis: a case-control study.
AB  - A hospital-based pair-matched case-control study was carried out at Government
      Medical College Hospital, Nagpur to estimate the effectiveness of bacillus of
      Calmette-Guerin (BCG) vaccination against tuberculous meningitis. The study
      included 92 cases of tuberculous meningitis in the age group of 0-12 years and
      equal number of controls, matched for age, sex and socio-economic status. The
      protective effectiveness and prevented fraction were higher for the subjects in
      the age group of 0-6 years, males and subjects from upper strata of socio
      economic class. The overall vaccine effectiveness and prevented fraction were
      estimated to be 86.54% (70.38-93.88%) and 65.54% (39.22-80.64%) respectively.
      Results of this study thus indicated that BCG vaccination was highly effective
      against tuberculous meningitis and played significant role in its prevention, in
      this population.

PMID- 9019080
TI  - Tuberculosis--an underestimated cause of ileal perforation.
AB  - One hundred and thirteen specimens of Ileum received over the last 3 years (1990
      92) were reviewed histologically and analysed to determine the aetiology of
      perforation. Perforations were seen in all age groups varying from one month to
      75 years with a peak incidence during 3rd and 4th decades. Males were more
      frequently affected. Perforations were single or multiple involving the whole
      ileum. The highest incidence (52) was seen in enteric fever. Next in frequency
      (19) was tuberculosis. In 23 cases no specific aetiology could be identified.
      Other causes of perforation were injury and obstruction resulting from
      diverticulosis, intussusception adhesions and worms. A significantly high
      incidence (16.8%) of tuberculous perforation is noteworthy.

PMID- 9019081
TI  - Epidemiology and clinical presentation of abdominal tuberculosis--a retrospective
      study.
AB  - The epidemiology and clinical presentation of abdominal tuberculosis were studied
      retrospectively in 298 adult cases admitted in Safdarjang Hospital, New Delhi
      over a 3-year period. These constituted 17% of the total number of admissions for
      tuberculosis. Age at presentation was variable with maximum cases in 21 to 40
      year age group (58% of cases) with a mean age of 32.7 years. There was a slight
      female preponderance (57%). Sixty-three per cent were residing in urban areas.
      Pain abdomen, ascites and subacute intestinal obstruction were the commonest
      modes of presentation (34%, 30%, 28% respectively). Other clinical features
      included fever (21%), altered bowel habits (19%), weight loss (8%) and lump
      abdomen (6%). Acute intestinal obstruction and lower gastro-intestinal bleeding
      were uncommon (5% and 4% respectively). Co-existent pulmonary tuberculosis was
      seen in 16% cases. Histological evidence was available in 41% cases. Majority
      improved with conservative management with only 21% requiring surgical
      intervention. Mortality recorded was 11%.

PMID- 9019082
TI  - Overview of tuberculosis of the female genital tract.

PMID- 9019083
TI  - Alcoholic hepatic impairment complicating treatment with hepatotoxic
      antituberculosis drugs.

PMID- 9019084
TI  - Treatment of tuberculosis.

PMID- 9019085
TI  - Superior vena caval syndrome due to pulmonary tuberculosis.

PMID- 9019086
TI  - Atypical spinal tuberculosis.

PMID- 9019087
TI  - A case of tuberculous infection of the placenta.

PMID- 9019088
TI  - Tuberculosis of the vulva.

PMID- 9019089
TI  - Tuberculous rheumatism.

PMID- 9019090
TI  - MRI in the early diagnosis of spinal tuberculosis.

PMID- 9019091
TI  - Review paper: coding systems in health care.
AB  - Computer-based patient data which are represented in a coded form have a variety
      of uses, including direct patient care, statistical reporting, automated decision
      support, and clinical research. No standard exists which supports all of these
      functions. Abstracting coding systems, such as ICD, CPT, DRGs and MeSH fail to
      provide adequate detail, forcing application developers to create their own
      coding schemes for systems. Some of these schemes have been put forward as
      possible standards, but they have not been widely accepted. This paper reviews
      existing schemes used for abstracting, electronic record systems, and
      comprehensive coding. It also discusses the remaining impediments to acceptance
      of standards and the current efforts to overcome them, including SNOMED, the
      Gabrieli Medical Nomenclature, the Read Clinical Codes, GALEN, and the Unified
      Medical Language System (UMLS).

PMID- 9019092
TI  - Natural language processing in medicine: an overview.
AB  - An overview is given of natural language processing applications in medicine. An
      attempt has been made to enumerate the most important and known international
      projects and to summarize their goals, principles, methods and results. A section
      is devoted to projects involving the Dutch language. A more general discussion
      about the two fundamental approaches concerning medical language understanding is
      provided. An extensive bibliography may be useful for those wishing to explore
      this research domain.

PMID- 9019093
TI  - Database and knowledge base integration--a data mapping method for Arden Syntax
      knowledge modules.
AB  - One of the most important categories of decision-support systems in medicine are
      data driven systems where the inference engine is linked to a database. It is,
      therefore, important to find methods that facilitate the implementation of
      database queries referred to in the knowledge modules. A method is described for
      linking clinical databases to a knowledge base with Arden Syntax modules. The
      method is based on a query meta-database including templates for SQL queries
      which is maintained by a database administrator. During knowledge module
      authoring the medical expert refers only to a code in the query meta-database; no
      knowledge is needed about the database model or the naming of attributes and
      relations. The method uses standard tools, such as C+2 and ODBC, which makes it
      possible to implement the method at many platforms and to link to different
      clinical databases in a standardized way.

PMID- 9019094
TI  - Machine learning of motor vehicle accident categories from narrative data.
AB  - Bayesian inferencing as a machine learning technique was evaluated for
      identifying pre-crash activity and crash type from accident narratives describing
      3,686 motor vehicle crashes. It was hypothesized that a Bayesian model could
      learn from a computer search for 63 keywords related to accident categories.
      Learning was described in terms of the ability to accurately classify previously
      unclassifiable narratives not containing the original keywords. When narratives
      contained keywords, the results obtained using both the Bayesian model and
      keyword search corresponded closely to expert ratings (P(detection) > or = 0.9,
      and P (false positive) < or = 0.05). For narratives not containing keywords, when
      the threshold used by the Bayesian model was varied between p > 0.5 and p > 0.9,
      the overall probability of detecting a category assigned by the expert varied
      between 67% and 12%. False positives correspondingly varied between 32% and 3%.
      These latter results demonstrated that the Bayesian system learned from the
      results of the keyword searches.

PMID- 9019095
TI  - A computerized medical standards system to help place impaired employees.
AB  - The paper describes a knowledge-distribution system that supports decisions on
      placement of impaired employees. The knowledge base consists of job profiles and
      medical profiles. The job profiles list tasks and the physical abilities they
      require. Twenty-one abilities describe the task demands. Active workers rated the
      exertion, frequency and importance of the physical ability required for each
      task. Thirty-nine work conditions were rated this way. Using identical scales,
      experts assessed the impact of impairments on the physical abilities of
      individuals and the tolerance of work conditions. The screening matches the job
      profile against the impairment profile. This process has been automated. The
      program lists tasks and work conditions that may compromise an impaired employee.
      This information can be used to accommodate employees, restrict duties or design
      a rehabilitation program. Also, the paper discusses the impact of the system on
      the operations of medical services within an organization.

PMID- 9019096
TI  - Instantiating and monitoring skeletal treatment plans.
AB  - Current emphasis on protocol-based care has stirred interest in planning research
      as applied to clinical medicine. However, many assumptions made in designing
      traditional planners and plan-execution algorithms do not hold in medical
      domains. The problems include the unpredictable nature of the domain, uncertainty
      and the variability in the utility of available actions, and the need for
      parallel and continuous execution of treatment plans. In the context of our
      research on intelligent monitoring and control, we developed an approach for plan
      instantiation and execution which takes advantage of readily available treatment
      protocols. The system, named SPIN, instantiates treatment protocols based on
      current context, executes plans and closed-loop control actions, monitors the
      execution of plans and actions, and modifies plan execution as necessitated by
      patient response. The system is incorporated in the Guardian system for intensive
      care patient monitoring and control. We address the strengths and limitations of
      the representation and the execution framework and discuss how the methodology
      may be improved and used in clinical practice.

PMID- 9019098
TI  - An object-oriented class library for medical software development.
AB  - The objective of this research is the development of a Medical Object Library
      (MOL) consisting of reusable, inheritable, portable, extendable C++ classes that
      facilitate rapid development of medical software at reduced cost and increased
      functionality. The result of this research is a library of class objects that
      range in function from string and hierarchical file handling entities to high
      level, procedural agents that perform increasingly complex, integrated tasks. A
      system built upon these classes is compatible with any other system similarly
      constructed with respect to data definitions, semantics, data organization and
      storage. As new objects are built, they can be added to the class library for
      subsequent use. The MOL is a toolkit of software objects intended to support a
      common file access methodology, a unified medical record structure, consistent
      message processing, standard graphical display facilities and uniform data
      collection procedures. This work emphasizes the relationship that potentially
      exists between the structure of a hierarchical medical record and procedural
      language components by means of a hierarchical class library and tree structured
      file access facility. In doing so, it attempts to establish interest in and
      demonstrate the practicality of the hierarchical medical record model in the
      modern context of object oriented programming.

PMID- 9019097
TI  - Development and evaluation of fuzzy criteria for the diagnosis of rheumatoid
      arthritis.
AB  - In 1987, the American Rheumatism Association issued a set of criteria for the
      classification of rheumatoid arthritis (RA) to provide a uniform definition of RA
      patients. Fuzzy set theory and fuzzy logic were used to transform this set of
      criteria into a diagnostic tool that offers diagnoses at different levels of
      confidence: a definite level, which was consistent with the original criteria
      definition, as well as several possible and superdefinite levels. Two fuzzy
      models and a reference model which provided results at a definite level only were
      applied to 292 clinical cases from a hospital for rheumatic diseases. At the
      definite level, all models yielded a sensitivity rate of 72.6% and a specificity
      rate of 87.0%. Sensitivity and specificity rates at the possible levels ranged
      from 73.3% to 85.6% and from 83.6% to 87.0%. At the superdefinite levels,
      sensitivity rates ranged from 39.0% to 63.7% and specificity rates from 90.4% to
      95.2%. Fuzzy techniques were helpful to add flexibility to preexisting diagnostic
      criteria in order to obtain diagnoses at the desired level of confidence.

PMID- 9019099
TI  - Hippocampal pathology and pathophysiology in temporal lobe epilepsy.
AB  - Hippocampal sclerosis involves the selective loss of some hippocampal cell
      populations, in a process that may disturb the excitatory/inhibitory balance of
      the remaining cells and produce the epileptic focus. Endfolium sclerosis is the
      minimal common pathological change found in epileptic patients with hippocampal
      damage. This subtle lesion is characterized by extensive dentate hilar cell loss
      without a similarly severe loss of dentate granule cells or hippocampal pyramidal
      neurons. We attempted to reproduce endfolium sclerosis experimentally by
      producing dentate granule cell seizure discharges with focal electrical
      stimulation in anesthetized rats, thus avoiding generalized seizure activity and
      motor convulsions. With this model, dentate hilar neurons and CA3 pyramidal cells
      were selectively and irreversibly injured, replicating the pattern of human
      endfolium sclerosis, with hilar cell damage and survival of dentate granule cell
      layer GABA-containing basket cells. This results in permanent granule cell
      disinhibition and hyperexcitability. Excitatory deafferentation of GABAergic
      basket cells was probably secondary to the loss of hilar mossy cells that
      normally excite the GABA neurons, rendering these neurons dormant. I propose that
      endfolium sclerosis in humans represents a selective loss of intrinsically
      vulnerable dentate hilar cells that normally govern dentate granule cell
      excitability and that this process leads to epileptiform discharges.

PMID- 9019100
TI  - Lions and hyenas in love.

PMID- 9019101
TI  - Lions and hyenas in love.

PMID- 9019102
TI  - What's in a (compound) name?

PMID- 9019104
TI  - Conjoint Report. To the North Carolina Medical Society and the North Carolina
      Commission for Health Services.

PMID- 9019103
TI  - Taking a stand on pain management.

PMID- 9019105
TI  - Medicine as a mission.

PMID- 9019106
TI  - Patient-centered care. A collaborative approach.

PMID- 9019107
TI  - Physician-assisted suicide. Lessons learned from the Kevorkian trials.

PMID- 9019109
TI  - Most anesthesiologists no longer restrict clear fluids for eight hours before
      elective surgery.

PMID- 9019110
TI  - Survey of NC anesthesiologists regarding nature of fasting before elective
      surgery.

PMID- 9019111
TI  - Perinatal substance abuse within central North Carolina. A suburban-rural
      perspective.

PMID- 9019112
TI  - Wellness is key for diabetics. Don't let sick days get you down.

PMID- 9019114
TI  - Locked and loaded. Roger Castle's Gulf War syndrome.

PMID- 9019113
TI  - Opportunities for cooperation. A dialogue with the Saratov Medical University,
      Russia.

PMID- 9019115
TI  - My encounter with cancer. One woman's battle with cancer and today's health
      system.

PMID- 9019117
TI  - New views of sickle cell disease.

PMID- 9019116
TI  - Interval to cancer diagnosis following "negative" transthoracic fine needle
      aspiration biopsy.

PMID- 9019118
TI  - "All but death, can be adjusted". Ma Huang (ephedrine) adversities.

PMID- 9019119
TI  - The impact of somatosensory input on autonomic functions.

PMID- 9019120
TI  - Reward structure as a moderator of the relationship between extraversion and
      sales performance.
AB  - The proposition that the relationship between extraversion and sales performance
      is moderated by reward structure was investigated. Specific hypotheses were
      tested with data obtained from 152 sales representatives. One group of sales
      representatives was rewarded primarily for obtaining new sales and another
      primarily for retaining customers. Data pooled across the 2 groups showed that
      extraversion did not correlate significantly with either new sales or customer
      retention. However, moderator analysis revealed that extraversion was positively
      associated with the dimension of performance that was explicitly rewarded but not
      with the nonrewarded dimension. A significant correlation between
      conscientiousness and new sales, but not between conscientiousness and customer
      retention, was found with the pooled data. As expected, relationships between
      conscientiousness and sales performance were not moderated by reward structure.

PMID- 9019121
TI  - Moderating effects of personal and contextual factors in age discrimination.
AB  - The researchers explored personal and contextual factors that inhibit or
      facilitate the use of older worker stereotypes in a selection context. The
      authors suggest that older worker stereotypes are more likely to be used and
      influence applicant evaluations when raters are biased against older workers,
      when raters do not have the cognitive resources to inhibit the use of age
      associated stereotypes, or when applicants apply for age-incongruent jobs. The
      researchers explored the extent to which raters differing in older worker bias
      make discriminatory decisions about young or old individuals applying for age
      typed jobs under conditions of high- and low-cognitive demands. A laboratory
      study was conducted with 131 undergraduate students who evaluated applicants in a
      simulated employment context. Results indicated that older worker bias, cognitive
      busyness, and job age-type interact to affect the extent to which applicant age
      plays a role in selection decisions.

PMID- 9019122
TI  - Organization of information in memory and the performance appraisal process:
      evidence from the field.
AB  - No studies dealing with cognitive processes in performance appraisal have been
      conducted in field settings, raising questions about the usefulness of this
      research for practice. The field experiments described here, conducted in 2
      organizations, were designed to evaluate interventions that laboratory research
      has suggested enable raters to better organize performance information in memory:
      structured diary keeping and structured recall. After these interventions, raters
      had more positive reactions to the appraisal process, were better able to recall
      performance information, and produced ratings that were less elevated and better
      able to discriminate between and within rates. The implications of these results
      for practice and for cognitive research in performance appraisal are discussed,
      along with the limitations of these studies and the problems with criteria for
      evaluating ratings in the field.

PMID- 9019124
TI  - Would reading an account of an event refresh your memory?
AB  - Witnesses to an event who have prepared an account of it may be given an
      opportunity to review this account or to read another account before testifying.
      The authors investigated the effects of this procedure by using participant
      accounts and both accurate and misleading experimenter-prepared accounts. Another
      experimental group did not review any account. Participants given no opportunity
      to refresh memory were less accurate in free recall than participants who
      refreshed memory, but they were equally accurate in answering direct questions.
      Measures of consistency between performance on testing sessions showed that the
      opportunity to review a self-produced account resulted in more consistent
      performance than nonreview. Results of this study have important implications in
      pretrial witness preparation.

PMID- 9019123
TI  - Effects of trial complexity on decision making.
AB  - The ability of a civil jury to render fair and rational decisions in complex
      trials has been questioned. However, the nature, dimensions, and effects of trial
      complexity on decision making have rarely been addressed. In this research, jury
      eligible adults saw a videotape of a complex civil trial that varied in
      information load and complexity of the language of the witnesses. Information
      load and complexity differentially affected liability and compensatory decisions.
      An increase in the number of plaintiffs decreased blameworthiness assigned to the
      defendant despite contrary evidence and amount of probative evidence processed.
      Complex language did not affect memory but did affect jurors' ability to
      appropriately compensate differentially worthy plaintiffs. Jurors assigned
      compensatory awards commensurate with the plaintiffs' injuries only under low
      load and less complex language conditions.

PMID- 9019125
TI  - Adults' understanding of young children's testimony.
AB  - In many legal settings, judges and jurors must gain an understanding of a crime
      solely on the basis of a child's testimony. In the present experiment, the
      authors examined adults' ability to understand young children's accounts of a
      past event. Adults were given a transcript of an interview with a 3- and a 6-year
      old child. In addition, half of the adults were given a summary of the event
      (informed) and half were not (naive). All adults were asked to extract as many
      details as possible from the transcripts. Naive adults were also asked to write a
      paragraph summarizing what happened during the event. Overall, adults gleaned
      more information from transcripts of 6-year-olds than from transcripts of 3-year
      olds. Furthermore, naive adults were more accurate than informed adults. The
      authors concluded that adults' ability to understand children's testimony
      increases as a function of the child's age and may be impaired rather than
      enhanced by additional sources of information.

PMID- 9019126
TI  - Psychological antecedents of escalation behavior: effects of choice,
      responsibility, and decision consequences.
AB  - Research on escalation behavior has proposed that choice of an initial course of
      action, responsibility for decision outcomes, and negative decision consequences
      are necessary conditions for the escalation effect to occur. This proposition was
      tested in a sample of 257 undergraduates. Results show that although
      responsibility and negative decision consequences contribute to the escalation
      effect, they are not necessary conditions for escalation to occur. Escalation is
      also observed when a choice is overruled, and there are positive consequences for
      the implemented course of action. The escalation bias is greatest when the
      consequences are inconsistent with participants' expectations. These results are
      consistent with a self-justification explanation.

PMID- 9019127
TI  - [Brief history of the Spanish Society of Microbiology. III. From 1977 to 1983].
AB  - This is the third article of the series about the history of the SEM. It
      comprises the period from 1977 to 1983. During that period, the 7th and 8th SEM
      national congresses took place in Cadiz (1979) and Madrid (1981) respectively,
      and other scientific meetings and activities of the specialized sections were
      organized. The executive committees of the SEM over that period are listed. SEM
      membership during that period increased significantly.

PMID- 9019128
TI  - [The journal of the Spanish Society of Microbiology, 1945-1995].
AB  - The official journal of the Spanish Society for Microbiology (SEM) was first
      published in 1947, under the name Microbiologia Espanola. Until 1984 the journal
      was published by the SEM jointly with the Institute <<Jaime Ferran>> (from the
      National Research Council, CSIC). In 1985 SEM started by itself to publish a new
      journal named Microbiologia SEM, which may be considered the continuation of the
      former. From 1985 on the journal has increased both the quality and variety of
      its articles. At the beginning, most articles were in Spanish. Gradually,
      articles in English have been majority, to increase international readership.
      Currently the journal is published quarterly, with more than 500 pages per year.

PMID- 9019129
TI  - Language, gender and science.

PMID- 9019130
TI  - [Ways of doing science].

PMID- 9019131
TI  - Ancestral relationships of the major eukaryotic lineages.
AB  - Molecular systematics has revolutionized our understanding of microbial
      evolution. Phylogenetic frameworks relating all organisms in this biosphere can
      be inferred from comparisons of slowly evolving molecules such as the small and
      large subunit ribosomal RNAs. Unlike today's text book standard, the "Five
      Kingdoms" (plants, animals, fungi, protists and bacteria), molecular studies
      define three primary lines of descent (Eukaryotes, Eubacteria, and
      Archaebacteria). Within the Eukaryotes, the "higher" kingdoms (Fungi, Plantae,
      and Animalia) are joined by at least two novel complex evolutionary assemblages,
      the "Alveolates" (ciliates, dinoflagellates and apicomplexans) and the
      "Stramenopiles" (diatoms, oomycetes, labyrinthulids, brown algae and
      chrysophytes). The separation of these eukaryotic groups (described as the
      eukaryotic "crown") occurred approximately 10(9) years ago and was preceded by a
      succession of earlier diverging protist lineages, some as ancient as the
      separation of the prokaryotic domains. The molecular phylogenies suggest that
      multiple endosymbiotic events introduced plastids into discrete eukaryotic
      lineages.

PMID- 9019132
TI  - Diversity of eukaryotic microorganisms: computer-based resources, "The Handbook
      of Protoctista" and its "Glossary".
AB  - The kingdom Protoctista comprises some 30 phyla, including the eukaryotic
      anaerobes that permanently lack mitochondria, the Phylum Archaeprotista, with its
      three classes: (i) Archamoebae, e.g., Pelomyxa, Mastigina, (ii) Metamonada, e.g.,
      Giardia, Pyrsonympha, and (iii) Parabasalia, e.g., Trichomonas, Calonympha, and
      the Phylum Microspora (Microsporidia), e.g., Vairimorpha. These and all algae,
      protozoa, labyrinthulids, "water molds" (oomycota, plasmodiophorans,
      hyphochytrids, chytrids, etc.) and other eukaryotes excluded from plants, animals
      and fungi are detailed in the Handbook of Protoctista. The Illustrated Glossary
      of Protoctista contains descriptions of the morphology and taxonomy of these
      microorganisms, including the many equivalent and homologous structures with
      different names. The Glossary has also been made into a Macintosh-compatible CD
      ROM disk.

PMID- 9019133
TI  - [Preliminary studies on the design of retroviral vectors for substitutive gene
      therapy].
AB  - We have studied the effect that exerts on the Moloney murine leukemia virus (Mo
      MLV) viral cycle the deletion of the 13 bases that constitute the inverted repeat
      (IR) present at the external U3 region of the pre-proviral DNA. Whereas
      supernatants of wild type- and modified virus-producing cells contained similar
      amounts of viral particles, the deleted viruses showed a 100 to 1000-fold
      decreased infectivity. To determine how the deletion interfered with the
      infective capacity of the virus, different steps of the viral cycle were studied
      using deleted viruses. The deletion affected neither reverse transcription nor
      the entry of the DNA into the cell nucleus; however, the integration of the pre
      proviral DNA into the host genome was reduced to undetectable levels. These
      results open a pathway to the construction of Mo-MLV-derived retroviral vectors
      for gene targeting purposes.

PMID- 9019134
TI  - [Importance of Chlamydia pneumoniae as a new respiratory pathogen].
AB  - The incidence of Chlamydia pneumoniae as a cause of respiratory tract infection
      was evaluated in a one-year prospective study in 142 patients with community
      acquired pneumonia. An indirect immunofluorescence method which detects
      antibodies in acute and convalescent serum samples was used. Serological evidence
      of current infection was a four-fold rise in IgG antibody titer or a positive IgM
      fraction. C. pneumoniae was the causative pathogen in nine patients. This result
      is similar to those obtained in other studies and suggests that C. pneumoniae is
      a common etiological agent of community-acquired pneumonia in the studied area.

PMID- 9019135
TI  - [Effect of nutritional conditions on the viscosity and emulsifying capacity of V2
      7 biopolymer from Volcaniella eurihalina].
AB  - Volcaniella eurihalina is a moderately halophilic bacterium able to produce an
      exopolysaccharide (EPS) under different culture conditions. Rheological behavior
      of 1% EPS solutions varied depending on the conditions under which EPS were
      produced. The maximum viscosity was reached when maltose was used as carbon
      source. Limitations of phosphorus and sulfur also increased its viscosity power.
      On the other hand, the addition of residual oil products to the culture medium
      enhanced the production of this biosurfactant polymer.

PMID- 9019136
TI  - Genetic determinants for the biosynthesis of nisin, a bacteriocin produced by
      Lactococcus lactis.
AB  - In the past, the genetic determinants for nisin biosynthesis were thought to be
      plasmid-located. However, it has been shown that production of nisin, immunity to
      nisin, and other properties such as the fermentation of sucrose, are encoded on
      70 kb conjugative transposons that are chromosomally located. The
      extrachromosomal location of the nisin genes has not been substantiated by
      experiments that unequivocally show plasmid transfer. Two natural variants of
      nisin have been identified, nisin A and nisin Z, encoded by the genes nisA and
      nisZ, respectively. Both genes have been cloned and sequenced and differ only in
      a single base pair. Approximately 12 kb downstream from the structural gene has
      been cloned and sequenced, and a further 10 genes involved in the biosynthesis of
      nisin have been identified. The nisB and nisC gene products are involved in nisin
      maduration, the nisT in its secretion and the nisP in its processing. The nisR
      and nisK gene products have a regulatory role and the nisI, nisF, nisE and nisG
      are involved in immunity to nisin. All these genes display significant homology
      to the corresponding genes of the related lantibiotics subtilin and epidermin.

PMID- 9019137
TI  - Optimization of the production of a bacteriocin from Haloferax mediterranei Xia3.
AB  - The optimal conditions for the production of the halocin H1, a 31 kDa bacteriocin
      like molecule produced by the extreme halophilic Archaea Haloferax mediterranei
      Xia3 active against Gram-negative haloarchaea, was characterized. The physico
      chemical conditions required for the optimal production of halocin H1 are similar
      to those found in the habitat in which the microorganism was isolated: 20% salt
      concentration and temperature range between 37 and 42 degrees C. Optimal
      antimicrobial activity was obtained using 0.5% of N-Z amine E as nutrient.

PMID- 9019138
TI  - Dipodascus magnusii (Saccharomycetes) contains multiple glucose-6-phosphate
      dehydrogenases with different NAD+/NADP+ dependencies.
AB  - A cell-free extract of a morphologically unstable strain of Dipodascus magnusii
      contained six proteins with activity of glucose-6-phosphate dehydrogenase
      (G6PDH). Two of these proteins displayed only NADP(+)-dependent activity, two
      could utilize both NAD+ and NADP+, but had higher activity with NAD+, and two
      possessed only NAD(+)-dependent activity. When the cultivation was carried out in
      the presence of monoiodoacetic acid, only two proteins with G6PDH activity were
      produced, one of them NAD(+)-dependent and the other NADP(+)-dependent. In all
      cases, NAD(+)-dependent activity was less stable in the presence of proteinases
      than was the NADP(+)-dependent activity.

PMID- 9019139
TI  - Origins and evolution of antibiotic resistance.
AB  - The massive prescription of antibiotics and their non-regulated and extensive
      usage has resulted in the development of extensive antibiotic resistance in
      microorganisms; this has been of great clinical significance. Antibiotic
      resistance occurs not only by mutation of microbial genes which code for
      antibiotic uptake into cells or the binding sites for antibiotics, but mostly by
      the acquisition of heterologous resistance genes from external sources. The
      physical characteristics of the microbial community play a major role in gene
      exchange, but antimicrobial agents provide the selective pressure for the
      development of resistance and promote the transfer of resistance genes among
      bacteria. The control of antibiotic usage is essential to prevent the development
      of resistance to new antibiotics.

PMID- 9019140
TI  - Separation and partial purification of beta-glucosidase and two endoglucanases in
      Aspergillus niveus.
AB  - The thermotolerant Aspergillus niveus strain RMF 7883 was grown in Czapek medium,
      with filter paper cellulose. The proportion of mycelial-bound to extracellular
      enzymes was studied. Most of the beta-glucosidase (80.9%) and endoglucanases
      (78.3%) activities were extracellular. The extracellular endoglucanases and beta
      glucosidase were separated and partially purified by Sephadex G-100 gel
      filtration, followed by ion exchange chromatography on CM-trisacryl M. Two
      extracellular endoglucanases, EG I and EG II (130 kDa and 35 kDa, respectively),
      and beta-glucosidase (194 kDa) were isolated from culture filtrate.

PMID- 9019141
TI  - A second Escherichia coli gene with similarity to gapA.
AB  - An open reading frame has been found downstream of the ald gene at 31 min in the
      Escherichia coli chromosome and has been designated gapC because of its high
      similarity with gapA (min 39, encoding glyceraldehyde-3-phosphate dehydrogenase),
      and with gapB (min 62, a gene with high similarity to gapA, encoding erythrose-4
      phosphate dehydrogenase). The gapC gene (min 31) encodes a polypeptide of 204
      amino acids, 126 residues shorter than glyceraldehyde-3-phosphate dehydrogenase.
      In this 204-codon open reading frame several amino acids important for catalysis
      are conserved. However, the cofactor binding site is lost. The results illustrate
      a case of a gene, encoding a glycolytic enzyme, for which at least three copies
      maintaining a certain degree of similarity are apparent in the E. coli genome. It
      seems likely that the genes encode products with different cellular functions.
      The origin of these three copies of the gap gene by horizontal transfer or by
      duplication of an ancestral gene is discussed.

PMID- 9019142
TI  - [Transesophageal echocardiography. A critical appraisal. How to avoid false
      diagnoses].
AB  - In this study the authors make a critical appraisal of transesophageal
      echocardiography. A retrospective analysis was made of the transesophageal
      echocardiographic performed in the Thoracic Surgery Center of S. Joao Hospital,
      Oporto, over a period of approximately five years. The authors report the
      limitations and complications of this diagnostic tool with particular emphasis on
      the leading causes of pitfalls. Between October 1990 and December 1995, 1282
      examinations were performed in our echocardiographic laboratory, mean age 49.6 +/
      14 years (5-86), 57% of the patients were female and 43% male. A biplane
      transducer was used in these examinations. Patient absenteeism was 2% and only
      one major complication occurred in a patient with an aortic dissection. Pitfalls
      are of special concern with this technology. The new esophagic window over the
      heart and the high quality of the cardiac images, depicting structures and
      anatomic details inaccessible, or difficult to be observed by transthoracic
      echocardiographic, led to the major causes of transesophageal echocardiographic
      pitfalls. Once recognized, most of the pitfalls can be avoided. In what concerns
      our experience, examples of the most common pitfalls are illustrated.

PMID- 9019143
TI  - [A new classification of lower infarcts with important prognostic significance].
AB  - BACKGROUND: The initial therapy of acute myocardial infarction is often
      determined by the electrocardiogram. OBJECTIVE: To evaluate a classification of
      inferior myocardial infarctions according to the first electrocardiogram. DESIGN
      AND SETTING: Prospective study in a coronary care unit. PATIENTS: 116 patients
      admitted due to a first acute myocardial infarction of the inferior wall.
      METHODS: "Type 1" electrocardiogram was defined as ST segment elevation without
      distortion of the QRS. Patients were considered "type 2" when, besides ST segment
      elevation, they presented a distortion of the terminal portion of the QRS complex
      in two inferior leads. MAIN RESULTS: Twenty-nine patients (25%) were considered
      "type 2". These patients were older and had worse Killip class than "type 1". The
      mortality rate was 1.2% in "type 1", and 24.1% in "type 2" (p = 0.0002). After
      multivariate analysis, which included Killip class, age, smoking, type of
      electrocardiogram and fibrinolysis, the type of electrocardiogram remained
      significantly predictive of death (p = 0.014). CONCLUSIONS: We conclude that
      "type 2" electrocardiogram is an independent predictor of adverse outcome in
      inferior infarctions. Further investigation is needed concerning its implications
      in the clinical management of these patients, although reperfusion therapy is
      warranted.

PMID- 9019144
TI  - [Infectious endocarditis caused by Q fever. Apropos of a clinical case].
AB  - Endocarditis is a rare, but some times fatal, complication of Q fever. Its
      diagnosis is difficult and it is based on non-specific cardiac findings and a
      high title of phase I antibodies. The treatment is based on tetracyclines alone
      or in combination with cotrimoxazole, for long periods of time. The therapeutic
      efficacy is evaluated by the measurement of phase I antibodies, every three
      months. The relapses are frequent despite the long period of antibiotic therapy.
      We report what is probably the first case of Q fever prosthesis endocarditis in
      Portugal, as a complication following an acute episode of Q fever.

PMID- 9019145
TI  - [Transesophageal echocardiographic analysis of the spectral two- dimensional
      ultrasonic characterization of masses in the left atrium].

PMID- 9019146
TI  - [Pulsed Doppler flow of the left atrial appendage and cerebral vascular accident.
      Multiplanar transesophageal echocardiographic study].

PMID- 9019147
TI  - [Relation of left ventricular mass, volume and systolic function in three
      dimensional transesophageal echocardiography. Multifactorial linear regression
      analysis].

PMID- 9019148
TI  - [Two-dimensional echocardiographic myocardial densitometry in the grey scale.
      Study of factors dependent on the sample and the inter- and intra-observer
      technical variability].

PMID- 9019149
TI  - [Heterogeneity of pulsed Doppler tissue pattern and regional left ventricular
      function in a normal population].

PMID- 9019150
TI  - [Three-dimensional echocardiography reconstruction of the left ventricle using 3
      different myocardial encoding techniques with Doppler tissue imaging].

PMID- 9019151
TI  - Are you considering replacing you old film archive?

PMID- 9019152
TI  - Use of 16S rRNA analysis to investigate phylogeny of methylotrophic bacteria.
AB  - Small-subunit rRNAS from 24 gran-negative methylotropic bacteria have been
      sequenced. A phylogenetic tree was constructed on the basis of sequence
      similarities by using a weighted least-mean-square difference method. The
      methylotrophs were separated into coherent clusters in which bacteria in each
      group shared physiological characteristics.

PMID- 9019153
TI  - Spirochetes from digital dermatitis lesions in cattle are closely related to
      treponemes associated with human periodontitis.
AB  - Digital dermatitis (DD), first described in 1974 by Cheli and Mortellaro (R.
      Cheli and C. Mortellaro, p. 208-213, in Proceedings of the 8th International
      Conference on Diseases of Cattle, 1974), is a major problem in diary cows and
      beef cattle causing significant economic losses worldwide. Lesions are typically
      found at the volar skin proximal to the heel bulbs. Microscopic examination of
      biopsies or touch preparations of these lesions revealed a variety of different
      bacterial morphotypes including significant numbers of spirochetes which often
      represent the predominant morphotype. We used comparative 16S rRNA sequence
      analysis to determine the diversity and phylogeny of these hitherto unclassified
      DD spirochetes. Results indicate that those lesions looked at so far contained at
      least five spirochetal phylotypes, all clustering within the genus Treponema.
      Phylotype DDKL-4 was nearly identical (99.4% similarity) to that of a
      nonpathogenic human treponeme, T. phagedenis. Two phylotypes DDKL-3 and DDKL-13
      were closely related to those from treponemes commonly found in human
      periodontitis lesions, i.e., T. denticola and T. vincetii, exhibiting 95 and 98%
      similarity, respectively. The other two phylotypes, DDKL-12 and DDKL-20, had no
      close relatives to any cultivable treponemal species but clustered to previously
      described group IV oral treponemes. Preliminary analysis using in situ
      hybridization with fluorescently labeled oligonucleotide probes against smears
      from DD biopsies revealed that from all lesions analyzed so far, T. denticola
      like spirochetes were detected in the highest proportion of all spirochetal
      morphotypes.

PMID- 9019154
TI  - The LAZ3/BCL6 oncogene encodes a sequence-specific transcriptional inhibitor: a
      novel function for the BTB/POZ domain as an autonomous repressing domain.
AB  - Rearrangements and mutations of the LAZ3/BCL6 gene are the most frequent events
      associated with diffuse large-cell lymphoma, a particular class of non-Hodgkin's
      lymphomas. This gene encodes a putative regulatory protein with six COOH-terminal
      Kruppel-like zinc fingers and a NH2-terminal hydrophobic region, the so-called
      BTB/POZ domain, which mediates homo- as well as heterotypic interactions in other
      related proteins. Recently, a consensus binding sequence has been defined using
      the isolated LAZ3/BCL6 zinc finger region produced in bacteria. To understand the
      normal and oncogenic functions of LAZ3/BCL6, we examined its properties as a
      transcription factor. We thus demonstrated that its full-length product binds to
      the same consensus sequence, although the BTB/POZ domain decreases this activity,
      at least in vitro. In transient transfection experiments, the LAZ3/BCL6 protein
      exerts a repressive effect, both as a wild-type protein on its own target
      sequence and as a GAL-4 fusion protein. Furthermore, our results indicate that
      the BTB/POZ domain plays a prominent role in the mediation of this activity.
      Indeed, on the LAZ3/BCL6 cognate sequence, deletion of the BTB/POZ domain
      diminishes the repressive function. Conversely, as a GAL-4 chimera, the isolated
      LAZ3/BCL6 BTB/POZ domain appears nearly as efficient as the entire protein at
      inducing transcriptional repression. Taken together, these findings demonstrate
      that the LAZ3/BCL6 is a sequence-specific transcriptional repressor and point to
      a novel function for the BTB/POZ region, at least in LAZ3/BCL6, as an autonomous
      transcriptional inhibitory domain.

PMID- 9019156
TI  - Proximal promoter region of the junB gene mediates attenuation of serum
      inducibility in Src-transformed cells.
AB  - Transcription of the junB gene is rapidly and transiently induced following
      stimulation of susceptible cells by growth factors in serum. Our previous studies
      demonstrated that serum inducibility of junB and other immediate-early genes is
      markedly attenuated in fibroblasts chronically transformed by the viral Src
      oncoprotein. Moreover, attenuation of junB induction occurs at the
      transcriptional level. To characterize further the molecular mechanisms of this
      attenuation, various full-length and recombinant junB constructs were transfected
      into normal and viral Src-transformed rat fibroblasts. A stable transfection
      system was used to faithfully reproduce regulation of the junB gene. Analyses of
      pooled populations of stably transfected cells demonstrate that sequences between
      -89 and +32 (relative to the transcriptional start site) are sufficient to confer
      both serum inducibility of the junB gene in normal cells and its attenuation in
      viral Src-transformed cells. By contrast, attenuation of c-fos serum inducibility
      by Src transformation involves element(s) distinct from regulatory elements
      identified previously in the c-fos promoter. These results identify a proximal
      promoter region of the junB gene that is involved in a novel negative regulation
      of its transcription.

PMID- 9019155
TI  - Coordination of transcription factors, NF-Y and C/EBP beta, in the regulation of
      the mdr1b promoter.
AB  - The expression of mdr genes that encode P-glycoprotein, an integral membrane drug
      transporter, has been associated with the emergence of the multidrug resistance
      phenotype during treatment with cancer chemotherapeutic drugs. To understand the
      regulation of the mdr genes, the murine mdr1b promoter has been isolated and
      characterized in our laboratory. Three nuclear protein binding sites that
      interact with nuclear proteins present in both drug-sensitive and -resistant
      murine macrophage-like 1774.2 cells have been localized to the promoter. In this
      report, transcription factor NF-Y has been identified as binding to the Y-box
      sequence in site 1 and as a major factor in the regulation of the murine mdr1b
      promoter in the mouse adrenal cell line, Y-1, that endogenously expresses the
      mdr1b gene. The expression of CCAAT/enhancer binding protein beta (C/EBP beta) in
      Y-1 cells augmented mdr1b promoter activity and resulted in an increased level of
      mdr1b mRNA. The effect of C/EBP beta expression on mdr1b promoter activity was
      sensitive to mutations in the Y-box, suggesting that coordination of NF-Y with
      C/EBP beta is required for further activation of the mdr1b promoter. Our studies
      have indicated that NF-Y is a critical factor for the mdr1b promoter, and its
      coordination with other factors, such as C/EBP beta, could be an important
      mechanism involved in mdr1b gene expression.

PMID- 9019157
TI  - Cloning and functional characterization of the chicken c-ros promoter.
AB  - Our previous study has shown that chicken c-ros is specifically expressed in
      certain epithelial cells of kidney, intestine, lung, bursa, thymus, and testis,
      and the expression is regulated temporally and spatially. To explore the
      molecular basis for the regulation of c-ros expression, we have cloned and
      characterized the chicken c-ros promoter. The most 5' c-ros cDNA was isolated and
      sequenced. Using the 5' cDNA as a probe, three genomic DNA clones containing the
      5' c-ros cDNA sequence were isolated. Primer extension and RNase protection
      analysis were used to map the transcription initiation site for the c-ros mRNA in
      kidney and intestine. The sequence of the 1.3-kb region upstream of the
      initiation site contains TATA and CAAT boxes at 26 and 54 nucleotides,
      respectively, upstream of the initiation site. In addition, transcription factor
      binding sites for AP1, AP2, and Oct1 and several direct and inverted repeats are
      present within 1 kb upstream of the initiation site. The 1.3-kb DNA, when placed
      upstream of the chloramphenicol acetyltransferase gene, was shown to be
      functionally active. Serial deletions of this putative c-ros promoter allowed us
      to define a minimum c-ros promoter and to identify positive and negative
      regulatory regions. Using two oligonucleotides corresponding to a positive
      regulatory and potential factor binding region, we have demonstrated, by gel
      mobility shift experiments, their specific binding to nuclear extracts from
      kidney, intestine, and thymus. The binding pattern corresponds to the tissue
      specificity and temporal control of c-ros mRNA expression.

PMID- 9019158
TI  - Nuclear localization signals, DNA binding, and transactivation properties of
      quail Pax-6 (Pax-QNR) isoforms.
AB  - We reported previously the characterization of Pax-QNR/Pax-6 products expressed
      in the avian neuroretina. Five proteins (48, 46, 43, 33, and 32 kDa) were
      characterized, among which the 33 and 32 kDa proteins are devoid of the paired
      domain. In contrast to the 48-kDa (containing an alternative paired exon 4a) and
      46-kDa proteins exclusively located in the nucleus, the 43- (in which the paired
      exon 5 is spliced out), 33-, and 32-kDa proteins were also found in the
      cytoplasmic compartment. We report the identification of two nuclear targeting
      sequences: the basic LKRKLQR region (amino acids 206-212) located in the NH2
      terminus of the homeodomain used by the p43 and 33/32 kDa proteins; and the
      paired exon 5 sequence. A case of human aniridia, where arginine 208 of LKRKLQR
      is mutated into a tryptophan, has been reported recently. We introduced this
      mutation into the Pax-QNR p46, p43, and p33/32 proteins. No effect on the nuclear
      localization or in transactivation potential of the proteins could be observed.
      Among the several Pax-QNR isoforms characterized, only p46 exhibited DNA-binding
      and transactivating properties on the Pax-QNR promoter. Deletions of parts of the
      protein showed that the Pax-6 transactivation domain is located in the carboxyl
      terminus of the protein.

PMID- 9019159
TI  - Differential expression of gas and gadd genes at distinct growth arrest points
      during adipocyte development.
AB  - The characterization of growth arrest-associated genes has revealed that cells
      actively suppress mitotic growth in response to extracellular signals. Mouse 3T3
      L1 cells growth arrest at multiple distinct points during terminal
      differentiation to adipocytes. We examined the expression of growth arrest
      specific (gas) and growth arrest- and DNA damage-inducible (gadd) genes as a
      function of 3T3-L1 growth arrest and adipocyte development. These growth arrest
      associated genes are differentially expressed throughout adipocyte development.
      Some of the gas/gadd genes are preferentially expressed in a subset of growth
      arrest states. In contrast, gas1 and gas3 are expressed in serum-starved
      adipoblasts, contact-inhibited adipoblasts, and post-mitotic adipocytes. However,
      in post-mitotic adipocytes, gas1 and gas3 are induced in response to nutrient
      deprivation, not altered growth status. gas6 is an exception to the general
      concordance of mitotic growth arrest and gas/gadd expression in that gas6 is
      preferentially expressed during the clonal expansion of postconfluent
      adipoblasts. Combined, the expression patterns indicate that growth arrest
      associated genes are regulated by numerous signal transduction pathways
      throughout a discrete developmental transition.

PMID- 9019160
TI  - Sequence requirements for alpha-fetoprotein gene expression during liver
      regeneration.
AB  - The alpha-fetoprotein (AFP) gene is expressed in fetal liver and in adult liver
      undergoing regeneration or tumorigenesis. It has been shown previously that three
      distal enhancers, a proximal promoter, and a dominant negative postnatal
      repressor element are required for the tissue-specific and developmental
      regulation of AFP gene expression. Using transgenic mice, we have determined the
      sequence requirements for AFP gene induction during liver regeneration. Two DNA
      sequences were found in all transgenes appropriately regulated in response to
      liver regeneration: a distal sequence between 1010 and 838 bp upstream of the
      structural gene and a proximal sequence within 118 bp of the transcriptional
      initiation site. In situ hybridization analysis showed that transgene expression
      during liver regeneration was first found in all hepatocytes and then localized
      to perinecrotic hepatocytes surrounding the central vein. This pattern of
      expression is reminiscent of that observed after birth for the transgenes,
      suggesting that repression of AFP gene expression after birth and liver injury
      may be regulated by similar mechanisms.

PMID- 9019161
TI  - Nitric oxide-releasing agents and cGMP analogues inhibit murine erythroleukemia
      cell differentiation and suppress erythroid-specific gene expression: correlation
      with decreased DNA binding of NF-E2 and altered c-myb mRNA expression.
AB  - Differentiation of murine erythroleukemia (MEL) cells induced by hexamethylene
      bisacetamide (HMBA) and DMSO was inhibited by several structurally unrelated
      nitric oxide (NO)-releasing agents and two membrane-permeable cGMP analogues.
      Since the effect of the NO-releasing agents was augmented by a cGMP
      phosphodiesterase inhibitor, at least some of their effect appeared to be
      mediated by activation of cytosolic guanylate cyclase. The drugs did not globally
      block differentiation since hemin-induced differentiation was undisturbed. In
      HMBA-treated cells, the NO-releasing agents and cGMP analogues reduced beta
      globin and delta-aminolevulinate synthetase mRNA expression and inhibited the
      late down-regulation of c-myb mRNA that is required for HMBA-induced
      differentiation of MEL cells; the regulation of c-myc mRNA was not changed by the
      drugs. Nuclear run-off analyses showed that the drugs inhibited the HMBA-induced
      changes in beta-globin and c-myb transcription rates, and transient transfection
      of a reporter gene construct demonstrated that the drugs inhibited HMBA-inducible
      enhancer function of the alpha-globin control region, which contains binding
      sites for the erythroid transcription factors NF-E2 and GATA-1. The NO-releasing
      agents and cGMP analogues largely prevented HMBA-induced increases in DNA binding
      of NF-E2, whereas DNA binding of GATA-1 and SP-1 was not affected. The inhibition
      of erythroid gene expression by NO and cGMP analogues may be physiologically
      important under conditions of high NO production by endothelial cells and
      macrophages, i.e. during acute or chronic inflammation.

PMID- 9019162
TI  - Heregulin (HRG)-induced mitogenic signaling and cytotoxic activity of a HRG/PE40
      ligand toxin in human breast cancer cells.
AB  - The heregulins (HRGs) are a family of growth factors that bind direction to erbB3
      and erbB4 and induce tyrosine phosphorylation of erbB2 via receptor
      heterodimerization. Since erbB2, erbB3, and erbB4 (erbB2-4) are often
      overexpressed in human breast cancer cells, we produced recombinant HRGs and a
      HRG-based ligand toxin to investigate the signaling events triggered by HRGs and
      the ability of these ligands to specifically target such cells. Recombinant HRG
      beta 2 stimulated the tyrosine phosphorylation of erbB2-4 in ZR-75-1 human breast
      cancer cells. This was accompanied by the tyrosine phosphorylation of Shc and the
      formation of complexes between Shc and the adapter protein Grb2. Complexes were
      also detected between Shc and erbB2-4. However, GRb2 was detected in erbB2 and
      erbB4 but not erbB3 immunoprecipitates. Thus, these receptors exhibit mechanistic
      differences in their coupling to Ras signaling, and HRG beta 2 administration
      triggers multiple inputs into the Ras signaling pathway, involving receptor-Grb2,
      receptor-Shc, and Shc-Grb2 complexes. HRG beta 2 addition also stimulated the
      association of erbB3 with phosphatidylinositol-3-kinase. In accordance with the
      activation of key mitogenic signaling pathways, HRG beta 2 stimulated the
      proliferation of MCF-7 and T-47D human breast cancer cells. Moreover, when tested
      for the ability to stimulate cell cycle re-entry of T-47D cells arrested under
      serum-free conditions, HRG beta 2 was more effective than insulin, previously the
      most potent mitogen identified using this system. Finally, a HRG beta 2 PE40
      ligand toxin was constructed and found to exhibit cytotoxic activity against
      human breast cancer cells overexpressing erbB3 alone or in combination with erbB4
      and/or erbB2.

PMID- 9019163
TI  - Overexpression of cyclin A in the mammary glands of transgenic mice results in
      the induction of nuclear abnormalities and increased apoptosis.
AB  - Aberrant expression of several cyclin genes has been demonstrated to be
      associated with many types of tumors. To determine the capacity of cyclin A to
      function as an oncogene in vivo, wild-type and mutant cyclin A proteins were
      specifically overexpressed in the mammary glands of transgenic mice using
      regulatory sequences from the ovine beta-lactoglobulin gene. Several lines of
      transgenic mice were generated that expressed human cyclin A or a nondegradable
      mutant version of human cyclin A, in which the amino-terminal 89 amino acids
      encompassing the cyclin destruction box were removed. The cyclin A transgene
      products were localized in the nuclei of mammary epithelial cells, and the
      transgenic mammary glands had an increase in cyclin A- and cdk2-associated H1
      kinase activity. Many mammary epithelial cells in the transgenic glands exhibited
      nuclear abnormalities, including multinucleation and karyomegaly, which were
      suggestive of preneoplastic alterations. The abnormalities were more severe in
      mammary glands of the mutant cyclin A transgenics, which expressed a stabilized
      cyclin A protein. In situ analysis of mid-lactation mammary gland sections
      revealed increased numbers of apoptotic cells in the transgenic glands. Double
      transgenic animals were generated that expressed both the mutant human cyclin A
      and human cdk2 transgenes, and a more pronounced phenotype resulted. The bigenic
      mammary glands exhibited focal areas of hyperplasia, as well as a greater
      incidence of apoptosis than observed in the single transgenic glands,
      demonstrating in vivo cooperation between these genes in transformation and
      apoptotic signaling pathways.

PMID- 9019165
TI  - p53-binding proteins in squamous cell carcinoma and normal human keratinocytes.
AB  - In squamous cell carcinomas (SCCs), the tumor suppressor protein p53 is
      frequently overexpressed. The overexpression of p53 is often due to a mutation in
      the p53 gene; however, increased levels of p53 protein can be observed in the
      tumors without p53 gene mutations. In normal human keratinocytes, p53 is a
      multiconformational protein. The different conformations of p53 can be identified
      by their reactivity with epitope-specific, anti-p53 monoclonal antibodies. This
      study provides evidence that the different p53 conformations seen in human
      keratinocytes bind to distinct cellular proteins. Proteins that bind p53 in
      normal human keratinocytes were compared with p53-binding proteins from cells
      derived from SCC tumors by immunoprecipitation of [35S]methionine-labeled and
      32P(i)-labeled cell lysates using a panel of anti-p53 monoclonal antibodies. In
      one tumor, the SCC cells contained a protein of Mr 30,000 bound to p53 that was
      not seen in normal human keratinocytes. Cells derived from a separate SCC did not
      have the Mr 30,000 protein but did contain two proteins of Mr 15,000 and Mr
      16,000, which were not seen in normal human keratinocytes. The immunofluorescent
      staining pattern of cultured normal human keratinocytes, cells derived from two
      SCCs, as well as the original tumors from which the cells were derived, was also
      examined. The immunofluorescent staining of the cells derived from the tumors and
      the tumors themselves was different from that seen in normal cultured
      keratinocytes and normal epidermis. These studies suggest that there are
      alterations in the proteins that bind to p53 in SCCs.

PMID- 9019164
TI  - Transgenic mice bearing the polyomavirus large T antigen directed by 2.1 kb of
      the keratin 19 promoter develop bronchiolar papillary tumors with progression to
      lung adenocarcinomas.
AB  - Keratin 19 is an intermediate filament protein produced by cells of simple
      epithelia and basal cells of stratified epithelia of different organs. These cell
      types are associated with important human cancers. We have used the keratin 19
      promoter to target the expression of the polyomavirus (Py) large T-antigen, an
      immortalizing oncogene known to bind to the tumor suppressor retinoblastoma gene
      product, to epithelial cells. Individuals of the transgenic mouse line K19PyLT-6
      developed one or two nodules in one of their lungs. By histology, the nodules
      were papillary tumors that consisted of nonciliated epithelial cells of the
      terminal bronchioles. In addition, infiltrates emanating from the nodules were
      consistent with the development of pulmonary adenocarcinomas. In situ
      hybridization techniques demonstrated large T-antigen expression in the tumors.
      Primary cultures were established from a lung tumor dissected from a K19PyLT-6
      transgenic mouse. These large T-antigen-expressing cell lines produced the
      keratin proteins reminiscent of the epithelial origin of the lung tumor. However,
      further molecular studies indicated that these cell lines did not express Clara
      cells or pneumocytes markers. s.c. injection of the cell lines into nontransgenic
      syngeneic mice produced tumors in 2 weeks that resembled malignant pulmonary
      adenocarcinomas. These animals, which display tumor progression in situ, and the
      cell lines derived thereof provide a useful system for the study of lung
      tumorigenesis.

PMID- 9019166
TI  - WT1 expression alters tumorigenicity of the G401 kidney-derived cell line.
AB  - Recent studies have implicated a loss of WT1 tumor suppressor gene function in
      the development of Wilms' tumor (WT). To determine the potential biological
      consequences of WT1 inactivation in these tumors, we transfected two different
      splice variant forms of this gene into the pediatric kidney-derived cell line
      G401. Introduction of this gene caused no detectable effects on the population
      doubling times of the cell line; proliferative capacity in soft agar was not
      significantly affected. However, the expression of this gene altered the
      morphology of the cells in culture and caused a significant suppression of
      tumorigenicity in the cells. Thus, the expression of WT1 in a pediatric kidney
      derived cell line lacking endogenous WT1 production caused demonstrable effects
      on its in vitro and in vivo growth properties. These data strengthen the concept
      for a central role for WT1 inactivation in the etiology of this disease.

PMID- 9019167
TI  - Cholesterol sulfate activates multiple protein kinase C isoenzymes and induces
      granular cell differentiation in cultured murine keratinocytes.
AB  - The accumulation of cholesterol sulfate (CS) in differentiating keratinocytes
      coincides with the expression of protein kinase C (PKC)-regulated granular layer
      differentiation markers both in vitro and in vivo. In this study, we examined the
      ability of Cs to induce differentiation marker expression in primary mouse
      keratinocytes and to modulate keratinocyte PKC isozymes (alpha, delta, epsilon,
      eta, and sigma). Treatment of basal keratinocytes with CS induced the expression
      of the granular layer proteins filaggrin and loricrin and decreased the level of
      the spinous keratin K1. CS stimulated cornification and blocked the induction of
      K10 in keratinocytes induced to differentiate by calcium. The induction of
      filaggrin and loricrin by CS corresponds to a granular layer differentiation
      program, where PKC activation occurs and was blocked by the PKC inhibitor GF
      109203X. Treatment of keratinocytes with CS caused PKC epsilon, eta, and sigma to
      be selectively lost from the cytosol fraction and increased in the cytoskeletal
      fraction. The loss of soluble PKC epsilon, eta, and sigma was rapid (1 h) and
      sustained (44 h). PKC alpha and delta were not redistributed. In vitro, CS
      induced kinase activity of PKC epsilon, eta, and sigma to a greater extent than
      did the phorbol ester 12-O-tetradecanoylphorbol-13-acetate for these isoforms.
      PKC alpha and delta were activated to a lesser extent by CS than by 12-O
      tetradecanoylphorbol-13-acetate. The translocation of PKC epsilon, eta, and sigma
      in intact cells treated with CS, together with the in vitro activation of
      recombinant PKC epsilon, eta, and sigma preferentially by CS, suggests a role for
      these isoforms in the induction of keratinocyte differentiation by CS.

PMID- 9019168
TI  - Properties of classic protein kinase C in human small cell lung carcinoma NCI
      H345 cells.
AB  - Bombesin-like peptides (BLPs) activate protein kinase C (PKC), which leads to
      proliferation in nonmalignant Swiss 3T3 cells. The purpose of this study was to
      determine if PKC expression in the classic human small cell lung carcinoma NCI
      H345 cell line, which has an autocrine growth loop involving BLPs, exhibited
      unique properties that could result in malignant behavior. PKC activity and
      phorbol dibutyrate binding in NCI-H345 cells had properties similar to other
      reports. PKC activity in the cytosolic fraction increased to 100% as cells
      proliferated through lag, log, and plateau growth states. However, during the
      first 3 days after plating (lag growth state), 40-50% of the PKC activity was
      membrane associated, indicating a substantial portion in an activated form,
      possibly a result of BLP autocrine stimulation. NCI-H345 cells expressed the PKC
      isoenzymes alpha, beta, delta, sigma, and eta, but not gamma or epsilon, a
      pattern different from Swiss 3T3 cells or normal brain. further characterization
      of the Ca2+/phospholipid-dependent (classic) PKC isoenzymes, alpha and beta,
      showed that PKC beta was predominantly cytosolic (80%) as expected, but PKC alpha
      was primarily membrane associated (80-90%). Exposure of NCI-H345 cells to 200 nm
      phorbol 12-myristyl 13-acetate rapidly (within 2 min) decreased cytosolic PKC
      activity, with no change in the particulate activity, but did not alter [3H]
      thymidine incorporation or subcellular distribution of PKC alpha or beta by
      Western blot. These results suggest altered PKC regulation in human small cell
      lung carcinoma NCI-H345 cells, which could contribute to their malignant
      behavior.

PMID- 9019170
TI  - Cell growth stimulation by the redox protein thioredoxin occurs by a novel helper
      mechanism.
AB  - Thioredoxins are a class of low molecular weight redox proteins that undergo
      reversible reduction-oxidation of two active-site cysteine residues with
      reduction catalyzed by the NADPH-dependent flavoenzyme thioredoxin reductase.
      Human thioredoxin has been shown to be identical to a previously reported
      leukemic cell growth factor. We now report that recombinant human thioredoxin
      added to minimal culture medium in the absence of serum stimulates the
      proliferation of a number of human solid tumor cell lines measured over several
      days. The concentration of thioredoxin producing half-maximal stimulation of MCF
      7 breast cancer cell proliferation was 350 nM, and the maximum stimulation
      occurred at 5 microM. The maximum increase in cell proliferation caused by
      thioredoxin was up to 90% of that seen with 10% bovine serum in the medium. There
      was a positive correlation between the ability of cell lines to proliferate in
      minimal medium, presumably, due to the autocrine production of growth factors by
      the cells, and the stimulation of proliferation by thioredoxin. Neither a redox
      inactive, mutant human thioredoxin, C32S/C35S, nor reduced Escherichia coli
      thioredoxin were able to stimulate MCF-7 cell proliferation. MCF-7 cell
      proliferation caused by human thioredoxin was completely abolished if the culture
      medium was changed each day. Antibody to thioredoxin blocked the cell
      proliferation caused by thioredoxin. Studies with 125I-labeled thioredoxin showed
      time-dependent binding to the surface of MCF-7 cells, but the binding was not
      saturable, indicating the absence of specific binding of thioredoxin to a cell
      surface receptor. Most of the thioredoxin associated with the cell could be
      released by trypsinization, and relatively little intact thioredoxin was taken up
      by the cell. The results of the study suggest that thioredoxin acts by a novel
      helper, redox mechanism to increase the cell proliferation response to growth
      factor(s) produced by the cell itself.

PMID- 9019169
TI  - Transforming growth factor beta 1 (TGF beta 1) is an autocrine positive regulator
      of colon carcinoma U9 cells in vivo as shown by transfection of a TGF beta 1
      antisense expression plasmid.
AB  - A transforming growth factor beta1 (TGF beta1) antisense expression plasmid under
      constitutive control of the Rous sarcoma virus promoter was introduced into the
      highly tumorigenic and invasive colon carcinoma U9A cell line, which uses its
      autocrine TGF beta1 as a growth-stimulating factor. Stable transfectants were
      infrequent, and only the K6 transfectant exhibited 39 and 33%, respectively, of
      the levels of TGF beta1 mRNA and active, secreted TGF beta1 protein of the
      parental line. K6 exhibited no change in TGF beta2 expression, and TGF beta3
      expression was not detected in either parental or transfectant cells. Compared to
      the parental line, the K6 antisense transfectant exhibited a 3-fold increase in
      lag time in anchorage-dependent colony formation. The parental line was 44 times
      as invasive through a collagen l-coated polycarbonate membrane in vitro as K6
      cells and, after s.c. injection at low-cell inocula, U9A cells induced tumors 75
      times as large in vivo as did the K6 antisense transfectant. The decreases in in
      vitro invasion and anchorage-dependent colony formation seen in K6 cells were
      largely reversed by the addition of TGF beta1. Tumors that did arise from the K6
      antisense transfectant cells had lost antisense TGF beta1 expression and
      expressed the same TGF beta1 mRNA levels as controls. U9A cells were more
      metastatic to the liver after intrasplenic injection than K6 cells. These
      findings demonstrate a role for autocrine TGE beta1 in colon cancer
      tumorigenicity and invasion. They also show that a relatively small decrease in
      TGF beta1 levels was enough to markedly decrease colon carcinoma cell
      aggressiveness. This is not unprecedented, as we had found in an earlier study
      that a small, 2-4-fold increase in TGF beta1 protein levels in human colon
      cancers correlated with disease progression to metastases (E. Friedman et al.,
      Cancer Epidemiol, Biomarkers & Prev., 4:549-554, 1995).

PMID- 9019172
TI  - Molecular cloning, expression, and developmental characterization of the murine
      retinoblastoma-related gene Rb2/p130.
AB  - The product of the retinoblastoma-related human gene Rb2/p130 is highly
      homologous with the product of the retinoblastoma tumor suppressor gene (pRb) and
      Rb-related p107. this homology is shared mainly in the pocket domain, a region
      that seems to play a key role in the functions of these proteins. Here we report
      the molecular cloning and initial characterization of the cDNA encoding the
      murine homologue of the human Rb2/p130 gene product. The 4.8-kb cDNA encodes a
      protein of 1125 amino acids that shows 90% indentity to that of the human
      protein. The Rb2/p130 mRNA is found to be expressed in all of the adult mouse
      tissues examined, with the highest level being detected in kidney and skeletal
      muscle. For the protein characterization, we used a polyclonal antibody raised
      against the COOH terminus of the human Rb2/p130 protein that also recognizes the
      mouse protein. In developing mouse embryos, the Rb2/p130 protein is expressed as
      early as day 10 of gestation and reached a peak of expression around day 13 of
      gestation, implying a developmental regulation of the Rb2/p130 gene in murine
      ontogeny.

PMID- 9019171
TI  - Involvement of stress-activated protein kinase in the cellular response to 1-beta
      D-arabinofuranosylcytosine and other DNA-damaging agents.
AB  - The cellular response to 1-beta-D-arabinofuranosylcytosine (ara-C) includes
      activation of Jun/AP-1, induction of c-jun transcription, and programmed cell
      death. The stress-activated protein (SAP) kinases stimulate the transactivation
      function of c-jun by amino terminal phosphorylation. The present work
      demonstrates that ara-C activates p54 SAP kinase. The finding that SAP kinase is
      also activated by alkylating agents (mitomycin C and cisplatinum) and the
      topoisomerase I inhibitor 9-amino-camptothecin supports DNA damage as an initial
      signal in this cascade. The results demonstrate that ara-C also induces binding
      of SAP kinase to the SH2/SH3-containing adapter protein Grb2. SAP kinase binds to
      the SH3 domains of Grb2, while interaction of the p85 alpha-subunit of
      phosphatidylinositol 3-kinase complex. The results also demonstrate that ara-C
      treatment is associated with inhibition of lipid and serine kinase activities of
      PI 3-kinase. The potential significance of the ara-C-induced interaction between
      SAP kinase and PI 3-kinase is further supported by the demonstration that
      Wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. The
      finding that Wortmannin treatment is also associated with internucleosomal DNA
      fragmentation may support a potential link between PI 3-kinase and regulation of
      both SAP kinase and programmed cell death.

PMID- 9019173
TI  - [Liquid ventilation--fact or fiction?].

PMID- 9019174
TI  - [Liquid ventilation with perfluorocarbons].
AB  - Clark and Gollan demonstrated impressively in 1966 the ability of
      perfluorchemicals (PFCs) to transport oxygen and to provide gas exchange across
      the alveolar capillary membrane. PFCs are used for two major medical indications:
      as artificial blood substitutes and as a medium for liquid ventilation. The PFC
      perflubron is additionally used as a contrast medium for diagnostic radiologic
      procedures. For the intravenous application perfluorocarbons have to be emulgated
      in phospholipids for the intrapulmonary application the sterile pure solution is
      used. Liquid ventilation can either be performed by a method known as total
      liquid ventilation (TLV), in which a device is utilised to ventilate with
      perfluorocarbon the previously perfluorocarbon-filled lung, or as partial liquid
      ventilation (PLV) in which a conventional mechanical gas ventilator is used to
      gas ventilate the partially perfluorocarbon-filled lung. A number of studies have
      demonstrated the efficacy of perfluorocarbon liquid ventilation in improving gas
      exchange and pulmonary function in a number of animal species in the setting of
      acute respiratory failure. In 1989 Greenspan reported on the first human liquid
      ventilation experience in a neonate. More recently human experiences for
      neonatal, paediatric and adult patients with acute lung injury have been
      reported. Since 1995 an FDA-approved study to examine the efficacy of PLV in
      severe respiratory failure in patients of all ages has been undertaken in the
      United States. The number of PLV-treated patients is still small; if PLV
      demonstrates its efficacy even in the ongoing human studies, it might be a very
      effective additional tool for treating severe acute lung injury.

PMID- 9019175
TI  - [Intubation requirements after rocuronium and succinylcholine].
AB  - OBJECTIVE: Rocuronium is a new non-depolarising steroidal muscle relaxant with a
      short onset time. The present study was undertaken to compare intubating
      conditions as well as onset and clinical duration of a single dose of 0.6 mg/kg
      (2 x ED95) with a single dose of 1 mg/kg suxamethonium (3 x ED95). METHODS: After
      obtaining informed consent and approval of the Ethics Committee, 40 adult
      patients (ASA I-III) participated in this study. After premedication with
      oxazepam, anaesthesia was induced with fentanyl and propofol and maintained with
      propofol, N2O and supplements of fentanyl as needed. Muscular relaxation was
      assessed by EMG recording of adductor pollicis muscle after supramaximal single
      twitch stimulation of the ulnar nerve every 10 s. Patients were allocated
      randomly to receive either rocuronium 0.6 mg/kg or suxamethonium 1 mg/kg. The
      following parameters were measured: intubating conditions 60 s after injection,
      onset time and clinical duration of neuromuscular block, % block at intubation,
      heart rate, blood pressure and arterial oxygen saturation. RESULTS: (mean +/-
      SD). Intubating conditions after rocuronium and suxamethonium were found to be
      clinically acceptable (excellent or good) in 90% of patients, though there was
      only a partial blockade of the adductor pollicis muscle with rocuronium (71 +/-
      23%) compared to suxamethonium (95 +/- 14%) (p < 0.05). The onset time and
      clinical duration of relaxation was shorter after suxamethonium (p < 0.05) and
      occurred at 0.8 +/- 0.2, 7 +/- 2.1 and 3.2 +/- 1.3, 29 +/- 11 min after
      suxamethonium and rocuronium respectively. CONCLUSION: At a dosage of 0.6 mg/kg,
      rocuronium has an onset time of about 3 min and a clinical duration of relaxation
      of nearly half an hour. These data are supported by various studies, while others
      show shorter times, probably due to different monitoring techniques. In spite of
      the pharmacodynamic differences between suxamethonium and rocuronium, the
      intubating conditions after administration of both compounds are comparable and
      develop at the same rate.

PMID- 9019176
TI  - [Effects of different kinds of ventilation and positioning measures on blood flow
      velocity in the middle cerebral artery].
AB  - OBJECTIVE: Aim of the present study was to quantify the influence of varying
      respiratory parameters and different body positionings on transcranial Doppler
      sonography (TCD) values. With the approval of the local ethics committee, 34
      patients without neurological deficits scheduled for an operation in supine
      position (n = 15) and in the so-called "rabbit-position" (RP, n = 19) were chosen
      for a prospective randomised investigation. METHODS: Prior to induction of
      anaesthesia, during the study and after extubation, the systolic (Vs), diastolic
      (Vd) and mean (Vm) of blood flow velocities as well as pulsatility (Vs - Vd)/Vm
      of the middle cerebral artery were determined by TCD. In addition mean arterial
      pressure and heart rate were monitored. Pulmonary airway pressures were observed
      during anaesthesia and CO2-partial pressure and central venous pressure (CVP)
      were determined by central venous line and blood samples. Anaesthesia was
      initiated with 5 mg/kg thiopental and continued with 0.8-1.2 vol% isoflurane in
      N2O/O2 = 2:1. After positioning all variables were recorded at 10-minute
      intervals with an inspiratory:exspiratory (I:E) ratio of 1:2, positive
      endexspiratory pressures (PEEP) of 0 and 10 cm H2O and an I:E ratio of 1:1 with 0
      and 10 cm H2O PEEP. The respirator was adjusted to maintain an endtidal pCO2 of
      40 mmHg. RESULTS: Neither different positioning of the patients, nor the
      alteration of respiratory parameters affected TCD variables in a significant way.
      No significant alterations were detected between the two groups of patients.
      Rising PEEP resulted in a minor but significant increase in CVP by an average of
      3 cm H2O in both groups. The respective positions produced different respiratory
      pressures. These were in the "RP-group", with and without PEEP, at an
      approximately 5 cm H2O higher level. All other parameters did not vary
      significantly. CONCLUSION: The findings of this study show that a positioning of
      patients in a so-called "rabbit position" during anaesthesia does not alter the
      rate of blood flow velocity in the middle cerebral artery. Moreover, the
      modification of important respiratory parameters, especially a rise of PEEP to 10
      cm H2O, had no significant influence on TCD values.

PMID- 9019177
TI  - [Changes in coagulation physiology and rheology after preoperative normovolemic
      hemodilution].
AB  - AIM: In a prospective randomised controlled trial the effect of preoperative
      normovolaemic haemodilution on coagulation, plasma viscosity and plasma protein
      levels was examined. METHOD: 50 patients undergoing gastrectomies were
      investigated (haemodilution group, n = 30; control group, n = 20). In the
      haemodilution group a haematocrit of 30% was aimed at. Blood was replaced by
      normovolaemic infusion of 6% hydroxyethyl starch 200/0.5. MAIN RESULTS:
      Haematocrit, colloid osmotic pressure, total serum protein, serum albumin and
      platelet count were significantly decreased intra- and postoperatively in the
      haemodilution group compared with control group (p < 0.01). All of these showed
      no differences between the two groups on the 7th postoperative day. Global
      coagulation parameters showed dilutional influences without significant
      differences between the two groups. Measurements of rheological parameters showed
      a statistically significant decrease in plasma viscosity in the haemodilution
      group compared with control group (p < 0.01). Haemodilution led to a marked
      reduction in the use of homologous blood (1 unit/haemodilution group; 10 units/
      control group). The average volume of 6% hydroxyethyl starch 200/0.5 administered
      per patient was 15.2 ml/kgKM/d (7.6-22.2 ml/kgKM/d) in the haemodilution group
      and 12.7 ml/ kgKM/d (8.4-17.7 ml/kgKM/d) in the control group. CONCLUSION:
      Haemodilution induced decreases in plasma coagulation, platelet count and plasma
      proteins did not cause any functional impairement and may just reflect dilution
      of these parameters. It seems that infusion of 6% hydroxyethyl starch 200/0.5 in
      an amount of 10-20 ml/kgKM/d does not result in a relevant decrease in
      coagulation parameters.

PMID- 9019178
TI  - Life without hemoglobin.

PMID- 9019179
TI  - [Arguments of Jehovah's Witnesses for refusing blood transfusions].

PMID- 9019180
TI  - [Oxygen supply and acid-base status in extreme anemia].

PMID- 9019181
TI  - [Assuring normovolemia in extreme hemodilution].

PMID- 9019182
TI  - [Administration of erythropoietin in extreme anemia].

PMID- 9019184
TI  - [Survival of very severe hemorrhage-induced anemia in a Jehovah's Witness].

PMID- 9019183
TI  - [Tolerating extreme intraoperative blood loss by a Jehovah's Witness patient].

PMID- 9019186
TI  - [Legal comment on refusal of blood transfusions].

PMID- 9019185
TI  - [Fatal hemorrhagic shock in a Jehovah's Witness].

PMID- 9019187
TI  - [Premedication].

PMID- 9019188
TI  - [N2O-induced acute funicular myelosis in latent vitamin B 12 deficiency].
AB  - The neurotoxicity of nitrous oxide ("laughing gas") had already been observed in
      1956 when using N2O in the long-term sedation of tetanus patients. In 1967
      Parbrook described leukopenic effects during long-term exposure to N2O. It was
      only in 1978 that further studies were conducted on myeloneuropathies and
      myelodepression under the influence of N2O. The basic cause is vitamin B12
      deficiency and the irreversible oxidation of coenzyme B12 by N2O. Between 1986
      and 1995 eight cases of acute funicular myelosis associated with latent vitamin
      B12 deficiency subsequent to nitrous oxide anaesthesia were reported. In our
      hospital, two further patients now have this disease. Two observations must be
      emphasised when assessing the 10 patients mentioned above: 1. There was no long
      term exposure to N2O (> 6 hrs); the periods of anaesthesia were between 1.5 and
      3.5 hrs. 2. Vitamin B12 deficiency was not known preoperatively, and there was no
      marked pernicious anaemia, so that the only pointers to the risk patients were
      supplied by the mean corpuscular haemoglobin (MCH) and the mean corpuscular
      volume (MCV) of the blood picture.

PMID- 9019190
TI  - Cytokines and inflammatory bowel disease. Proceedings from a workshop. London,
      United Kingdom, October 1995.

PMID- 9019189
TI  - [Treatment of drug-induced agranulocytosis with granulocyte colony stimulating
      factor (G-CSF) in a surgical intensive care unit].
AB  - Following repeated metamizole applications a 41-year old intensive-care patient
      suffering from severe craniocerebral trauma and sepsis developed a drug-induced
      agranulocytosis. Early G-CSF treatment reduced the neutropenic period to 4 days.

PMID- 9019191
TI  - [Isolated general malaise of unknown origin. A new syndrome].

PMID- 9019192
TI  - [Etiology of isolated general malaise].
AB  - Isolated general malaise (IGM) is defined as an imprecise sensation of feeling
      bad, without any other signs or symptoms that suggest even a diagnostic
      orientation. 137 patients who demanded medical help for IGM were selected and
      divided into three groups, according to their evolution: IGM of banal or benign
      cause; IGM of easy or attainable diagnosis; and IGM of difficult or prolonged
      diagnosis. The 37 patients of the latter group were integrated under the title of
      Unexplained General Malaise Syndrome (UGMS). The criteria of these syndromes are
      defined. The patients with UGMS were studied in order to make a diagnosis of its
      unknown disease, which was achieved in all cases except two. The non-specific
      symptoms that the patients with UGMS manifest and their relation to final
      diagnosis are described. When the final diagnosis was made, the number of
      diagnostic tests used, the time of hospitalisation and the derived economic cost
      was estimated in each case compared to the corresponding mean data, obtained.
      Depression as the most frequent aetiology detected in the patients with UGMS,
      should be the first consideration made in any evaluation.

PMID- 9019193
TI  - [Thoracic tuberculosis in adults. A comparative study of radiological findings of
      HIV seropositive and seronegative patients].
AB  - We compare the radiologic manifestations of chest TB in three groups of patients:
      HIV patients (52 cases), HIV negative patients (85 cases and 100 cases). Initial
      radiologic findings were similar in the two seronegative groups, even though
      there is an eight-year interval between both series. However, seropositive
      patients have a higher risk of acquiring the infection (x 2.25), of extrathoracic
      disease (x 4.22), of coincidental infections (p < 0.0002) and of progression of
      the disease p < 0.0003) than the normal population. Lymphadenopathy and miliary
      TB are much more common in the HIV positive patients (x 6.23 and x 44
      respectively). Cavitation, pulmonary scarring, volume loss and calcification are
      more frequent among the seronegative patients (p < 0.03), as well as pleural
      disease (p < 0.0001).

PMID- 9019194
TI  - [Lipoprotein profile in patients with isolated hyperuricemia].
AB  - There have been described abnormalities in the lipoprotein profile of
      hyperuricemic patients, it has not been clarified wether these abnormalities are
      due to the hyperuricemia or to the hyperlipidemia often associated to these
      patients. Our aim is to study the apolipoprotein profile in hyperuricemic
      patients without hyperlipidemia compared to a control population. 30
      hyperuricemic patients and 26 healthy controls. Measurements were of blood uric
      acid, total cholesterol, total triglycerides, creatinine, HDL-C, and VLDL
      cholesterol, triglyceride, Apo B, Apo CII and Apo CIII (1 and 2). Uric acid
      clearance and fractionated excretion were measured in 24 h. urine samples. No
      significant differences were found between hyperuricemic and control patients in
      cholesterol, triglycerides and apo B in VLDL, or LDL and HDL cholesterol. The
      levels of apo B, Apo AI levels and apo CIII/apo CII were similar in the
      hyperuricemic and controls. There are two types of hyperuricemic patients, one
      group associated to hyperlipidemia and would be included in the X Syndrome. The
      other group not associated to other metabolic abnormalities. Is important to
      distinguish between these two groups to define the prognosis of a given patient
      because the greater cardiovascular risk linked hyperuricemic patients could be
      related to the association to others cardiovascular risks factors.

PMID- 9019195
TI  - [Incorrect use of pressurized aerosols by health personnel].
AB  - Instruction and training of patients in the use of pressurized aerosols require a
      well-trained medical personal. This study was designed to analyze the quality of
      information about pressurize aerosols in medical personal responsible of patient
      training. Only 20% of the observed trainers made a correct instruction, whereas
      63% made more than two mistakes. Primary care nurses had a 100% index of correct
      training. As indicated in other studies, our result reveals a high index of
      incorrect training in the use of pressurizes aerosols by medical personnel, and
      this finding is more frequent ill hospital staff than in primary care personnel.

PMID- 9019196
TI  - [Recurrent ARDS in varicella pneumonia complicated by disseminated candidiasis in
      a pregnant woman].
AB  - Adult respiratory distress syndrome (ARDS) seems to be the common way from
      different etiologies. We describe the clinical evolution of an ARDS in a pregnant
      woman, initially due to Varicella Pneumonia which was complicated with
      Disseminated Candidiasis and recurrent ARDS. We review the nosocomial infection
      with Candida in ICU patients: the growing incidence, the diagnostic problems and
      the new standards for treatment.

PMID- 9019197
TI  - [Cutaneous vasculitis during primary myelofibrosis].
AB  - A leukocytoclastic cutaneous vasculitis in the course of an idiopathic
      myelofibrosis is reported. The cutaneous lesions that might appear in this
      hematological disease are discussed, including cutaneous infections, myeloid
      metaplasia and cutaneous infiltration due to the myeloproliferative process. We
      point out the rarity of cutaneous vasculitis during the course of primary
      myelofibrosis.

PMID- 9019198
TI  - [Surreptitious intake of diuretics as the cause of pseudo-Bartter's syndrome:
      apropos of a case and differential diagnosis].
AB  - We describe a 39 years old patient with a history of chronic symptomatic
      hypokalemia. She denied taking any drugs. She satisfied the clinical criteria for
      Bartter's syndrome and more precisely for Gitelman's syndrome: hypokalemia in the
      presence of inappropriately high potassium excretion, metabolic alkalosis,
      hyperreninemic hyperaldosteronism, hypomagnesemia with inappropriately high
      magnesium excretion, normocalcemia, hypocalciuria and normal blood pressure. A
      HPLC analysis detected the presence of furosemide in urine and chlorthalidone in
      urine and plasma samples. After the self administration of diuretics was stopped,
      the above alterations came back to normality. Prior to the verification of a self
      administration of diuretics, the patient showed clinical and biochemical
      parameters that oriented to surreptitious diuretic ingestion (Pseudo-Bartter's
      syndrome) not to Bartter's syndrome or Gitelman's syndrome, particularly the
      plasma potassium readily restored to normal by the administration of potassium
      chloride supplements, the increased plasma uric acid with low uric acid
      fractional clearance, the widely different urine and plasma electrolyte levels
      and the presence psychiatric disorders. The literature is reviewed and
      differential diagnosis, among this three syndromes, is made.

PMID- 9019199
TI  - [Fever of unknown origin as initial manifestation of Castleman's disease: apropos
      of 2 cases].
AB  - Castleman's disease is a rare lymphoproliferative disorder with a great range of
      clinical presentation and localization. It usually appears in young people and
      its etiology is unknown. Clinical features are not specific: fever, asthenia,
      hypochromic anemia and hypergammaglobulinemia. We report here two cases of
      Castleman's disease whose peculiarity lies in the fact that the first sign was
      fever of unknown origin. In both cases the use of a CT scan was very important
      for the diagnosis.

PMID- 9019200
TI  - [Pleural exudate as presentation of constrictive pericarditis].
AB  - An exudative pleural effusion is a very infrequent form of presentation of
      constrictive pericarditis, and it can induce diagnostic difficulties. We present
      a 71 year-old woman with a pleural effusion attributed to be due to congestive
      heart failure which does not respond to the treatment. The pleural fluid had
      biochemical characteristics of an exudate. The echocardiographic study showed
      severe constrictive pericarditis, and after the pericardectomy the pleural
      effusion completely resolved. The diagnostic suspicion of constrictive
      pericarditis in cases of exudative pleural effusion is of special interest
      because an specific and effective treatment is available.

PMID- 9019201
TI  - [Drug selection in hospitals. A model of reference in self-management of
      resources].
AB  - The practice of medicine today must balance the optimal use of new pharmaceutical
      agents with the need for cost containment. Hospital policy regarding therapeutics
      and its historical perspective are discussed. Various aspects of the operations
      of Pharmacy and Therapeutics Committees are presented. The potential benefits of
      a formulary system are therapeutic, economic and educational and it could lead to
      a uniformity of drug usage throughout a district. The role of Clinical
      Pharmacology to provide advice to both Institution and physicians in how
      therapeutic practice may be optimized is also stressed.

PMID- 9019202
TI  - [Adult respiratory distress syndrome caused by miliary tuberculosis in a patient
      with HIV infection].

PMID- 9019203
TI  - [Cerebral vasculitis and cocaine consumption].

PMID- 9019204
TI  - [Interferon-alpha and development of psoriatic arthropathy].

PMID- 9019205
TI  - [Acute pancreatitis and cocaine].

PMID- 9019206
TI  - [A case of solitary plasmocytoma of the humerus in complete remission for 15
      years].

PMID- 9019207
TI  - [Pulmonary hemorrhage after thrombolysis in acute myocardial infarction].

PMID- 9019208
TI  - [Acute bacterial meningitis in adults].

PMID- 9019209
TI  - [Acute bacterial meningitis in adults: a clinical and developmental analysis of
      100 cases].
AB  - BACKGROUND: Characterize clinical findings and outcome of acute bacterial
      meningitis (ABM) in adults, with special emphasis on nosocomial meningitis and
      meningitis in the elderly. METHODS: We reviewed the charts of all persons 14
      years of age or older in whom ABM was diagnosed in our hospital during a 12 and a
      half-year period. RESULTS: Ninety-seven patients were treated for 100 episodes of
      ABM, of which 23 percent were nosocomial and 27 percent occurred in elderly
      persons. Predisposing factors were present in 59 percent of the episodes. Fifty
      four percent had the classic triad of fever, nuchal rigidity, and change in
      mental status. Cerebrospinal fluid pleocytosis with a neutrophilic predominance,
      hypoglycorrhachia, and elevated protein levels were present in 62 percent of the
      episodes. A pathogen was identified in 62 percent of the cases, in a higher
      frequency in elderly persons (p < 0.05) and in patients who had not received
      antibiotics before the lumbar puncture (p < 0.05). Causal agents more frequently
      identified were: Streptococcus pneumoniae (27 percent) in community-acquired
      meningitis, coagulase-negative Staphylococci (35 percent) in nosocomial
      meningitis, and Strep. pneumoniae (33 percent) in elderly persons. Central
      nervous system (CNS) complications occurred in 18 percent of episodes, and 15
      percent developed systemic complications. The overall mortality rate was 9
      percent, higher among patients in whom CNS complications began within 24 hours of
      admission (p < 0.05). CONCLUSIONS: A high proportion of cases of ABM in adults
      are nosocomial, or affect elderly persons. The fatality rate is high,
      particularly among those who develop CNS complications at the onset of the
      disease.

PMID- 9019211
TI  - [Effect of the treatment with amlodipine on left ventricular hypertrophy in
      hypertensive patients].
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is one of the physiopathological
      effects of hypertension and one of the main risk factors for sudden death,
      myocardial infarction and congestive heart failure. Drugs to treat hypertension
      must not only reduce blood pressure, but also modify the facts which lead to
      ventricular hypertrophy. This study has been designed to assess the effect of
      amlodipine, a calcium-antagonist, on LVH in hypertensive patients. METHODS: 20
      hypertensive patients (mild to moderate, both sexes, mean age 45.0 yr) were
      included in a single-blind study. After an initial, four weeks placebo period,
      active treatment was given (amlodipine 5 mg a day). Dose titration was made after
      4-8 weeks to 10 mg a day if necessary and continued until the end of the study.
      Systolic (SBP) and diastolic blood pressure (DBP), as well as pulse rate (PR) and
      adverse events were recorded at every visit. Blood and urine analysis,
      catecholamine, plasmatic renin activity and Mode M echocardiography were made at
      the beginning and the end of the study. RESULTS: Only one patient was excluded.
      SBP and DBP showed a significantly fall (p < 0.001). In 80% of patients DBP fell
      under 90 mm Hg. Every echocardiographic parameter, but left ventricular diastolic
      dimension, showed significantly reductions at the end of the study: septum
      thickness (p = 0.001), posterior wall thickness (p = 0.001), left ventricular
      systolic dimension (p = 0.014), wall relative thickness (p = 0.015), shortening
      fraction (p = 0.009), left ventricular mass (p = 0.001) and corrected left
      ventricular mass (p = 0.001). Blood parameters did not modify. CONCLUSIONS:
      Amlodipine has a beneficial effect on LVH and also is an effective and safe drug
      to treat mild to moderate hypertension.

PMID- 9019210
TI  - [Cerebrovascular disease and associated risk factors].
AB  - In this report we are analysing the clinical history of 193 patients who were
      admitted to our medical department due to stroke during a period of two years.
      The patients were divided into two groups depending on wether they had ischemic
      or hemorrhagic pathology, analysing the presence of vascular risk factors in both
      groups. From the obtained results we have to point out, in both groups of
      patients, hypertension together with mellitus diabetes, giving clear proof of
      this, being the most frequent association of risk factors. We also have to point
      out the low percentage of patients with a lack of all the analysed risk factors,
      being also, that the average age was notably superior than the global.

PMID- 9019212
TI  - [Differentiated carcinoma of the thyroid gland in an area of endemic goiter.
      Clinical study and prognostic correlation].
AB  - OBJECTIVE: Differentiated thyroid Carcinoma is a relatively frequent malignant
      neoplasia with three histologic types: papillary, follicular, and Hurtle cell
      carcinoma. Although papillary is the most common type, in endemic goitre areas
      the frequency of follicular type increases. Up to now, the only European studies
      about clinical aspects of differentiated thyroid carcinoma in endemic goitre
      areas are those performed in the Bavarian region until 1983. As the province of
      Orense (assistance zone concerning to the Hospital Virgen del Cristal) is a zone
      of endemic goitre, we have analyzed clinical presentation features and prognostic
      correlation factors in patients with differentiated thyroid carcinoma living in
      this area. DESIGN: Retrospective study. Variables analyzed: 1) Age. 2) Sex. 3)
      Histologic type. 4) Tumor size. 5) Stage. 6) Presence of multinodular goitre. 7)
      Posttherapeutic disease persistence. 8) Recurrence. 9) Distant metastases. 10)
      Death attributed to thyroid carcinoma. PATIENTS: 61 cases of differentiated
      thyroid carcinoma, detected from 1983 to 1993. Mean follow-up period: 5 years
      (minimum 1, maximum 21). All patients were treated with total thyroidectomy
      followed by radioiodine ablation. RESULTS: 67.2% of papillary, 31.2% of
      follicular and 1.6% of Hurtle cell carcinoma. Male/female ratio: 1/4. Mean age:
      48.8 +/- 2.9 (M +/- ESM) in papillary and 55 +/- 3.2 in follicular. Tumor size
      was smaller in papillary: 2.2 +/- 0.2 vs 6.2 +/- 0.5 cm (p < 0.001). Papillary
      type was detected more frequently than follicular in stages I, II and III,
      whereas follicular prevailed in stage IV (p < 0.03). Positive correlation between
      age and size in papillary: r = 0.393 (p < 0.01) and similar tendency in
      follicular: r = 0.423 (p = 0.057). Multinodular goitre was more frequent in
      follicular: 47% vs 25% (p = 0.02). Free of disease cases after treatment: 81% of
      papillary (p < 0.05) and 42% of follicular. Stage correlated independently with
      disease persistence after treatment (p = 0.0006). Age was minor in free of
      disease group: 50.0 +/- 3.8 vs 65.3 +/- 3.8 (p = 0.01). CONCLUSIONS: In our area,
      papillary is the most common type, but follicular proportion is higher than
      reported from non endemic goitre areas. PC is a small tumor detected in stage I,
      whereas FC is large and detected in stage IV. Tumor stage is an independent
      prognostic factor. Frequent presence of multinodular goitre in patients with
      differentiated thyroid carcinoma suggests that in zones of endemic goitre,
      clinical attitude in multinodular goitre and solitary nodule must be similar.

PMID- 9019213
TI  - [HIV infection and lymphomatous meningitis].
AB  - Lymphomatous meningitis and lymphoma confined to the central nervous system are
      the most serious neurological diseases in patients with human immunodeficiency
      virus infection. The diagnosis is difficult and it is usually done with advanced
      systemic disease or when the chemotherapy is finished. During a ten month period,
      three patients with lymphomatous meningitis and HIV infection were diagnosed in
      an Infectious Diseases Unit. In one patient, was the initial clinical
      manifestation of Burkitt's lymphoma and in another, the diagnosis was concomitant
      with the neoplasm. In the last one, there was a meningeal recidiva afterwards he
      had received chemotherapy and, theoretically, cured his systemic lymphoma.
      Clinical, cytologic, immunologic and evolutive study of these three patients is
      done. It is discussed the meningeal prophylaxis usefulness with intrathecal
      chemotherapy.

PMID- 9019214
TI  - [A case of monoclonal gammapathy type IgD].
AB  - We refer in the present article, the first case found in our laboratory of
      Monoclonal gammapathy of the IgD type. A 47-year-old man presented at the
      emergency department with a history of malaise, lethargy, tiredness, thirstiness
      and obscure depositions. Clinical examination revealed a normocytic anaemia. The
      plasma urea was 423 mg/dl and the plasma creatinine was 15, 3 mg/dl. He was
      admitted to hospital with a diagnosis of acute renal failure. The later
      electrophoresis in serum revealed a little monoclonal band that was identified as
      IgD-lambda type by immunofixation electrophoresis. In urine electrophoresis was
      observed a beta-band. Bone marrow biopsy revealed a 20% of plasmocytic cells.
      Renal biopsy was compatible with myelomatose lesions. Osteolytic lesions were
      observed.

PMID- 9019215
TI  - [Streptococcus agalactiae infection in adults. Presentation of 3 cases].
AB  - The Streptococcus of the B group was considered during many years, as a women's
      prelabor pathogen and neonatus. Lastly an increase of the infections is observed,
      for this germ in adults, without being in connection with the pregnancy. The
      Streptococcus agalactiae, affect above all to patients, with any type of illness
      underlying. The most susceptible are the diabetics and focus of more habitual
      infection, the soft tissues and the bone. We described three cases of infection
      by Streptococcus agalactiae in adults picked up during two years, in a Service of
      Internal Medicine with 51 beds. We are revised Medline, from the year 1985, until
      1995, confirming the drop incidence of cases.

PMID- 9019216
TI  - [Parasitic delirium in patient with multiorganic pathology: a complex situation].
AB  - Delusion of parasitosis is often observed in people who usually take psychoactive
      drugs. Moreover, it can be present in infectious diseases or tumours of the
      central nervous system, metabolic disorders, deficiency and states systemic
      disorders, such as Systemic Lupus Erythematosus (SLE). The neuropsychiatric
      manifestations in SLE patients are common and constitute one of the criteria for
      the classification of SLE. Presentation as an acute organic mental syndrome is a
      clinical emergency and it is usually required the admission in the hospital. We
      report a case of delusion of parasitosis in a middle age woman diagnosed of SLE
      several years before and with previous corticosteroid therapy, right temporal
      arachnoid cyst, chronic Lyme disease and hypothyroidism. We analyse the different
      role of each pathology and the clinical practice difficulties in the management
      of these disorders.

PMID- 9019217
TI  - [Hepatoxicity caused by flutamide increased by hypotensive situation?].
AB  - We describe a 76-year-old male patient who developed a life-threatening acute
      hepatotoxicity possibly caused by flutamide, an antiandrogen drug given during
      the previous 10 months, in the scenario of a brief moderate hypotension secondary
      to atrial flutter. There was a sudden increase of liver enzyme levels AST = 4.521
      IU/L, ALT = 1.716 IU/L (normal values 0-37 and 0-40 respectively), prothrombin
      activity decreased to 16%, and also felt the platelet count, with significant
      haemorrhages. We hypothesize this was triggered as a consequence of the transient
      diminished supply of oxygen to the subclinically flutamide-damaged hepatocytes by
      the well-known mechanism of the cytochrome P450 (3A and 1A)-mediated formation of
      electrophilic metabolites, and the inhibitory effect of flutamide on
      mitochondrial respiration and ATP formation.

PMID- 9019218
TI  - [Current status of the treatment with thyroid hormones].
AB  - The main indication of thyroid hormone preparations is the treatment of
      hypothyroidism, ideally the goal of therapy is to restore the serum thyrotropin
      (TSH) concentration to a normal value. The optimal doses used to be stable, but
      several conditions may alter their requirements (reduced intestinal absorption,
      pregnancy,...). Levothyroxine therapy is also used in the benign nodular disease
      and after surgery in patients with thyroid cancer. The overtreatment with
      thyroxine and the problems related to bone mineral density seems of special
      importance.

PMID- 9019219
TI  - [False negatives of ADA in pleural tuberculosis].

PMID- 9019220
TI  - [Right pleural effusion as first manifestation of dissecting aneurysm of the
      aorta].

PMID- 9019221
TI  - [Hemoptysic expectoration and tuberculous arthritis].

PMID- 9019222
TI  - [Dyspnea as the only symptom in a Krukenberg tumor].

PMID- 9019223
TI  - [Recurrent edema and hypokalemia as form of presentation of cyclic Cushing
      syndrome caused by an adrenal adenoma].

PMID- 9019224
TI  - [Biliary infection and bacteremia caused by Haemophilus influenzae].

PMID- 9019225
TI  - [A case of choroid metastasis of cancer of the breast with an excellent response
      to chemotherapy].

PMID- 9019226
TI  - [Benign retroperitoneal schwannoma].

PMID- 9019228
TI  - [Value of ultrasound in diagnosis of post-traumatic heterotopic ossifications].
AB  - Heterotopic ossification is a non-neoplastic deposit of bone within soft tissue
      (myositis ossificans). The most common localized form is post-traumatic myositis
      ossificans. The ultrasonographic appearance of heterotopic ossification is
      characterized by highly echogenic areas with attenuation or complete
      disappearance of the acoustic signal distal to these areas. The size and extent
      of para-articular ossifications can also be evaluated, and the choice of the
      surgical approach is facilitated and damage to soft tissue minimized by the
      ultrasonographic examination.

PMID- 9019227
TI  - [O2 sensitive L-lactate biosensors with enzyme membranes based on L-lactate-2
      monooxygenase and L-lactate-oxidase with electroanalytic comparison].
AB  - O2-sensitive biosensors using oxidase membranes have acquired considerable
      electro-analytical importance. Since some of these O2-converting enzymes also
      produce H2O2, the use of additive reagents for the O2-free breakdown of the H2O2
      in the second reaction has repeatedly been reported. In contrast to L-lactate
      oxidase, L-lactate-2-monooxygenase converts its substrate without producing H2O2.
      Employing reference sera, tests with L-lactate showed that bioelectrochemical
      membrane electrodes with H2O2-producing enzymes of high purity, require no
      additive reagents to ensure reliable analysis. Continuous measurements with
      citrated blood using the principle of intermediate carrier analysis are
      demonstrated.

PMID- 9019229
TI  - [A new osteoblast cell culture system for standardized testing of biomaterials].
AB  - For in vitro testing of new biomaterials cultured fibroblasts are employed. In
      the case of the agar diffusion test survival of cells is involved in the presence
      of the material to be tested. Further statements on the biological effects of a
      biomaterial require the use of cell cultures adapted to the tissue concerned and
      the underlying problem being investigated. In the present study, an osteoblast
      cell culture system with which implant surfaces in contact with bone can be
      tested as required by the relevant standards is described. Test bodies made of
      titanium, polystyrene or copper were used in the conventional agar diffusion
      test, and were also overgrown with fibroblasts or a cell line of foetal human
      osteoblasts. For the agar diffusion test, the test criterion was the extent of
      the inhibition area on staining with neutral red, while for the overgrowth, the
      mean cell diameter and the number of cells was employed. The phenotype of the
      osteoblast cell line was determined immunohistochemically by means of alkaline
      phosphatase or immunohistologically by means of collagen I and osteocalcin.
      Calcification was demonstrated using the v. Kossa stain. In the case of the
      osteoblasts, a differentiation of a collagen I and alkaline phosphatase-positive
      phenotype over an osteocalcin-positive phenotype to an increase in calcium
      deposition was shown. As in the case of the agar diffusion test, direct
      overgrowth also revealed no cytotoxic effect for titanium and polystyrene. In
      contrast, a cytotoxic effect consisting in a decrease in the number of cells and
      also a left shift in the size distribution was observed for copper. The standard
      deviations of the individual tests were less for overgrowth than for the agar
      diffusion test. The culture system for osteoblast cells thus meets the criteria
      of the EN/DIN 30993-5 in terms of the quality and accuracy of the results
      obtained. In addition to excluding direct cytotoxicity, this test system offers a
      new possibility of examining the influence of the material on cell growth.
      Consequently, it permits a repeatable examination of proliferation and
      differentiation of the osteoblasts on each material surface.

PMID- 9019230
TI  - [Ceramic acetabulum components for hip endoprostheses. 2: Evaluating design and
      safety].
AB  - In the field of hip arthroplasty, there is a clearly recognizable towards the use
      of modular acetabular cups involving metal-backed sockets into which cup inserts
      made of either polyethylene or alumina ceramic (Biolox forte) can be fitted. The
      design aspects for this concept have already been discussed in [17]. In the
      present paper, we discuss the question of component reliability and the criteria
      for testing acetabular cups with ceramic inserts. To date, neither standards nor
      government regulations for ceramic cups are available. In the absence of such
      regulations, those laid down bei the American Food and Drug Administration (FDA),
      together with our own longterm experience with femoral ceramic heads are used as
      a guide for the testing of ceramic cup inserts.

PMID- 9019231
TI  - [Effect of music on gait symmetry of stroke patients on a treadmill].
AB  - The influence of rhythmic music on gait symmetry was investigated in 12 healthy
      subjects and 12 stroke patients with mild leg paresis walking on the treadmill.
      For the measurement, new insoles containing air-filled chambers developed by
      W.O.M were used. Symmetry deviation was determined as the mean signless
      difference between left and right swing phases of some 100 strides. In 6
      patients, the symmetry deviation decreased by more than 1% of the stride duration
      some 40 steps after switching on the music. The improvement correlated with the
      initial symmetry (r2 = 0.61) exclusively in the healthy controls. In order to
      differentiate individual predictors of the improvement in symmetry, such as
      cognitive performance in terms of recognizing the beat of the music and the motor
      performance in terms of synchronizing the movements of the legs to the music, we
      analysed foot tapping with the patient in the seated position. For both patients
      and healthy subjects, the mean time difference between beat and foot movement was
      less than +/-1/32 beat. Individual scatter of mean 8% correspond in the case of
      healthy subjects to the figures found in the literature for finger movements, and
      the corresponding figures for the patients are more than twice this. The
      individual synchronisation performance during walking to music correlates to that
      during foot tapping (r2 = 0.47) exclusively in the group of healthy controls.

PMID- 9019232
TI  - A comment on interim analyses in crossover trials.
AB  - In a recent issue of Biometrics, Cook (1995, Biometrics, 51, 932-945) considered
      the possibility of applying sequential analysis to 2 x 2 crossover trials and
      made a comparison with more conventional approaches. We believe this comparison
      to be misleading in a number of respects.

PMID- 9019233
TI  - Legal trends in bioethics.

PMID- 9019234
TI  - Use of electrospray ionization mass spectrometry and tandem mass spectrometry to
      study binding of F0 inhibitors to ceroid lipofuscinosis protein, a model system
      for subunit c of mitochondrial ATP synthase.
AB  - Ceroid lipofuscinosis protein (CLP), the major accumulating protein in several
      forms of ceroid lipofuscinosis, has an amino acid sequence that is identical to
      that of the F0 subunit c of normal bovine ATP synthase. Electrospray ionization
      mass spectrometry (ESI-MS) has shown that ovine CLP and normal bovine F0 subunit
      c are identical, including a 42 mass unit post-translational modification.
      Although the identity and the location of this modification have not been fully
      established in both species, CLP can be used as a convenient and a unique source
      of subunit c for studies of F0 inhibitor interactions by ESI-MS analysis.
      Analysis of mixtures of CLP incubated with several known F0 inhibitors showed
      that N, N'-dicyclohexylcarbodiimide and organotins bind covalently to CLP but
      interactions with oligomycin and venturicidin were not observed. The sulphydryl
      inhibitors, 2,3-dimethoxy-5-methyl-1,4,-benzoquinone (UQ0) and N-ethyl maleimide
      (NEM) were also shown to bind covalently to the protein. The binding
      stoichiometry and the relative rate of reaction were then determined for each
      inhibitor. Tandem mass spectrometry experiments performed on the [M+5H]5+ ion of
      the intact CLP and of the complexes UQ0-CLP and NEM-CLP allowed the
      identification of 80% of the CLP sequence and revealed that UQ0 and NEM are both
      bound to cysteine-64. This work shows the exceptional utility of ESI-MS in
      studies of the interaction of CLP with a range of inhibitors which are applicable
      to studies of the F0 component of ATP synthase.

PMID- 9019235
TI  - Sampling error in small-bore sheathless capillary electrophoresis/electrospray
      ionization mass spectrometry.
AB  - Two previously unreported sources of systematic error in electrokinetic injection
      caused by induced (hydrodynamic) flow in sheathless capillary
      electrophoresis/electrospray have been characterized for an interface constructed
      from 5 microns i.d. capillary column(s) with a 2-5 microns i.d. electrospray
      tip(s). The tip of a sheathless interface is usually exposed to the atmosphere,
      resulting in evaporation of buffer solvent and inducing flow inside the column;
      such flow can cause a significant underestimation of injection size for
      quantitative electrokinetic sampling by as much as 50%. This bias can be
      eliminated during the injection process by temporarily immersing the tip in
      buffer solvent. The second source of hydrodynamic flow results from the
      electrostatic pull exerted by the electrospray process on the buffer, reducing
      migration times. Reduction in migration times causes an overestimation of
      sampling volume if there are no electrospray processes during the sampling event.
      The magnitude of this effect is a complex function of electrophoretic and
      electrospray parameters and has been measured to be as high as 15% for 5 microns
      i.d. capillaries. The possible deterioration of electrophoretic resolution caused
      by these processes is not yet clarified.

PMID- 9019236
TI  - Characterization of two new matrices for matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Three structurally related compounds, 4-hydroxy-33-methoxyphenylpyruvic acid
      (HMPPA), indole-3 pyruvic acid (IPA), and indole-3-glyoxylic acid have been
      evaluated as matrix-assisted laser desorption/ionization (MALDI) matrices. HMPPA
      and IPA were found to be effective matrices for MALDI-MS analysis of proteins and
      peptides and have been characterized in this work. HMPPA was found to be a
      particularly good matrix for the analysis of proteins and peptides because of its
      tolerance towards impurities and the resulting sensitivity in MALDI-MS
      experiments. Analysis of model proteins and peptides, including those in
      biological fluid, are demonstrated.

PMID- 9019237
TI  - [Some examples of introductions and transfers of mollusks].
AB  - Human beings have always introduced non-indigenous species into new environments.
      Such is the case with shellfish, which the Romans, fine connoisseurs, transferred
      from France to Italy to mature. The Pacific oyster (Crassostrea gigas) and the
      Manila clam (Ruditapes philippinarum) are among the most significant examples of
      these introductions. The author examines the causes, conditions, results, and
      economic and biological repercussions of these examples. The well known cases of
      the introduction and implantation of new populations of molluscs are relatively
      recent, dating back to the beginning of this century. These movements result from
      an intensification of fishing activities, and the development of the mollusc
      industry and of transportation. The introduction of fish has been attempted for
      hundreds of species, whereas the introduction of molluscs has involved no more
      than a few dozen recorded species. Finally, with regard to the deliberate
      introduction of molluscs, none has led to significant ecological disruption, but
      on the contrary, has led to the establishment of permanent coastal activities
      which do not greatly disturb the natural biotopes.

PMID- 9019238
TI  - [International trade in bivalve mollusks and the current situation in France and
      in Europe].
AB  - Over the last century and a half, trade in shellfish has introduced into france
      four new species intended for aquaculture, as follows: -the Portuguese oyster
      (Crassostrea angulata) -the American clam (Mercenaria mercenaria) -the Pacific
      oyster (C. gigas) -the Manila clam (Ruditapes philippinarum). The development of
      hatcheries and air transport facilities has led to increased trade in these
      species among the countries of the European Union (France, Ireland, Italy, the
      Netherlands, Portugal, Spain and the United Kingdom); they are also imported from
      other countries (Morocco, Tunisia and Turkey). The species involved in this trade
      are the Pacific oyster, that flat oyster (Ostrea edulis), the Manila clam, the
      calico clam (R. decussatus) and the scallop (Pecten maximus). The reasons for
      such trade are economic (as markets and consumption habits differ from one
      country to another) and ecological (as areas suited to the growth of a species
      are not always those where natural reproduction is possible). Numerous problems
      still confront the economic participants, particularly the harmonisation of
      controls, the fair evaluation of disease risks and the adaptation of
      administrative procedures to biological constraints.

PMID- 9019239
TI  - [International trade in living penaeid shrimp between countries in the Pacific
      and the Atlantic areas and in Europe].
AB  - The tremendous development of penaeid shrimp culture across the world over the
      past twenty years has led to international trade in eggs, larvae and spawners of
      the best shrimp species for aquaculture. Trade has involved, in particular, the
      following species: -Penaeus japonicus from Japan to Europe, the Pacific Islands
      and South America -P. monodon from South-East Asia to almost all tropical
      countries -P. vannamei and P. stylirostris from countries along the Pacific coast
      of South and central America to the United States of America, the islands of the
      South Pacific, countries along the Atlantic coast of the Americas and certain
      countries in Africa. In the 1980s, research conducted by American and French
      teams enabled the breeding of stocks of spawners in captivity. This resulted in
      the establishment of lines of captive broodstock outside natural areas of
      distribution, and the development of new breeding farms in previously
      unproductive regions. Trade related to movements of these species is facilitated
      by the absence of legislation in most countries; even when such legislation does
      exist, it is not always applied. These practices have led to the rapid
      development of world shrimp production, but have also contributed to the
      dissemination of pathogens. In recent years, the occurrence of serious epizootics
      - occasioning heavy losses world-wide - has led to a more cautious approach
      involving trade of post-larvae obtained from captive broodstock in which thorough
      control measures have been implemented for known diseases. Trade in wild shrimp
      will probably be abandoned progressively, to avoid the risk of introducing new
      pathogens. The main challenges for research in the near future are the
      development of diagnostic tools, to enable continuous control of captive
      broodstock, and the selection of strains which are resistant to the principal
      pathogens affecting these species.

PMID- 9019240
TI  - Zebrafish cyclin E regulation during early embryogenesis.
AB  - Cyclin E cDNA, cloned from a zebrafish embryonic cDNA library, was used for
      analysis of cyclin E regulation during early embryogenesis. During the rapid cell
      cycles of the early cleavage stage, which lacks a G1 phase, the cyclin E mRNA,
      protein, and associated H1 kinase activity were found to be constitutive, in
      contrast to their reported cyclic behavior during the cycle of cultured mammalian
      cells. These results suggest an additional role for cyclin E during early
      embryogenesis, in addition to its established role during the G1/S transition in
      somatic cells. These results support previous identification of cyclin E in early
      cleaving Drosophila and Xenopus embryos, and provide for the first time the
      direct demonstration of constitutive cyclin E activity throughout the M/S cycles
      of the embryonic cleavage stage. Cyclin E mRNA was reduced during epiboly
      (approximately 6-8 hr postfertilization, HPF), concomitantly with a marked
      reduction in cell division rates. In contrast, the cyclin E protein and cyclin E
      CDK complexes remained constant throughout the first 24 hr, implying that the
      cyclin E protein is regulated post translationally and is not immediately
      affected by the levels of the corresponding mRNA. However, the cyclin E-CDK
      complexes present in 26 somite embryos (22 HPF) did not exhibit histone H(i)
      kinase activity. This discrepancy between high levels of cyclin E-CDK complexes
      and low enzymatic activity may be explained by the presence of putative cyclin E
      CDK inhibitory mechanism. Here we show that multiple levels of regulation of the
      cyclin E mRNA, protein, and associated kinase activity are present during the
      first 24 hr of zebrafish embryonic development.

PMID- 9019241
TI  - Differential expression of alpha-6 and other subunits of laminin binding
      integrins during development of the murine heart.
AB  - The development of the heart from a single heart tube to a four chambered organ
      with two separated unidirectional flows is a highly complex process. Events like
      looping, septation, tissue remodelling, and development of valves take place in a
      time period in which the heart already exerts its pump function. Adhesion of
      cells to each other and to their extracellular matrix as well as the capability
      to migrate in such a dynamic environment are extremely important. Integrins and
      extracellular matrix components have already been implicated in this process. In
      this report, we describe in detail the differential expression of the alpha-6
      integrin subunit during late murine heart development, e.g., in the process from
      looping to the end of septation. We compare mRNA and protein expression patterns
      with those of beta-1 and other subunits of laminin-binding integrins, alpha-3 and
      alpha-7. We show a constant and high expression of alpha-6 in the atrial
      myocardium and a decrease in expression in the ventricular trabecular myocardium.
      The compact myocardial wall and the ventricular septum do not express alpha-6,
      except for the myocardium of the distal outflow tract at early stages. Moreover,
      we describe expression of this integrin subunit in the endocardial cushions that
      contribute to the development of the atrioventricular and semilunar valves. We
      propose a role for the alpha-6-beta-1 laminin receptor in the adhesion of cells
      to their extracellular matrix at sites of high stress due to cardiac contraction
      or blood flow induced shear stress. Moreover, site specific endothelial
      expression within the heart and surrounding extracardiac tissue is discussed.
      This study suggests a distinct role for alpha-6-beta-1 in the heart and provides
      insight concerning probably important roles of integrins and their extracellular
      matrix ligands during embryonic development.

PMID- 9019242
TI  - High efficiency gene transfer into the embryonic chicken CNS using B-subgroup
      retroviruses.
AB  - Attempts to use replication-competent retroviruses to target genes to the chick
      CNS have met with limited success for injections performed prior to stage 14
      using A- or E-subgroup viruses. This study was aimed at improving CNS infection
      by varying the stage of injection, viral envelope subgroup, viral titer, and the
      presence or absence of a transgene and/or the polycation polybrene in the
      inoculum. RCASBP vectors were injected into the neural tube of stages 3-13
      embryos and protein expression was determined 9-48 hr later for forebrain,
      hindbrain, retina, and inner ear. Optimal injection parameters were defined which
      balanced good survival rates with high levels of transgene expression at early
      stages. The results demonstrate nearly complete expression of virus-mediated
      transgenes in neural tissues at stages 15-21 following injection of B-envelope
      RCASBP with polybrene at stages 7.5-12. This technique can now be applied to
      study the roles of genes in cell-autonomous events such as cell connectivity,
      physiology, and differentiation, as well as neural patterning and regional
      identity.

PMID- 9019243
TI  - Developmental expression of laminin-5 and HD1 in the intestine: epithelial to
      mesenchymal shift for the laminin gamma-2 chain subunit deposition.
AB  - We report the expression pattern of hemidesmosome-associated proteins laminin-5,
      composed of alpha 3 beta 3 gamma 2 chains, and HD1 in the developing mouse and
      human intestine, an organ in which variations in structure and function parallel
      morphogenesis and differentiation. Immunocytochemistry analysis revealed the
      coexpression of laminin-5 and HD1 at the basal pole of differentiating epithelial
      cells. Distinct noticeable variations occurring in the location of laminin alpha
      3 chain in development of mouse gut were stressed by the reverse transcriptase
      polymerase chain reaction data. A peculiar finding was also the location of
      laminin gamma 2 chain in the intestinal muscle coat. The cellular origin of
      laminin gamma 2 chain was examined by immunocytochemistry on interspecies hybrid
      intestines with specific antibodies recognizing mouse antigens. Complementary and
      sequential production of laminin gamma 2 chain was observed, by epithelial cells
      as establishment of the basement membrane occurs and by mesenchymal cells in the
      more differentiated organ. These results support the concept of mesenchymal
      involvement in deposition of basement membrane molecules, a crucial process for
      intestinal differentiation. Taken together these data provide the first evidence
      for the coexpression of hemidesmosome-associated proteins in the gut, a non
      stratified tissue.

PMID- 9019244
TI  - Troponin I isoform expression is developmentally regulated in differentiating
      embryonic stem cell-derived cardiac myocytes.
AB  - We studied troponin I (TnI) isoform expression in the mouse embryonic stem (ES)
      cell model of cardiogenesis as an essential first step to understanding the
      relationship between TnI isoform transitions and myofibrillar function. Cultures
      of differentiating ES cells were grown on coverslips to permit microscopic
      inspection of foci of spontaneously contracting cardiac myocytes developing in
      culture. TnI expression was followed over time to test whether the cardiac
      myocytes undergo the developmental pattern of expression characteristic of
      vertebrate cardiogenesis, in which slow skeletal TnI (ssTnI) is expressed
      initially, followed by induction of cardiac (cTnI) isoform expression. Cardiac
      TnI expression was examined using the cardiac-specific, monoclonal TI-1 antibody
      (Ab) while all striated muscle ThI isoforms were detected using the monoclonal TI
      4 Ab. Cardiac-specific TnI expression was detected in only 8% (8/96) of foci
      contracting less than 5 days while TI-4 positive staining was present in 95%
      (71/73) of foci. These results indicate that other striated muscle TnI isoforms
      were being expressed in most of the TI-4 positive staining foci. The proportion
      of contracting foci expressing the cardiac isoform increased steadily over time,
      such that 100% of foci contracting more than 20 days (13/13) stained positive
      with the TI-1 Ab. Dual labeling experiments with both TI-1 and TI-4 anti-TnI Abs
      in the same culture confirmed that within each foci, the area expressing cTnI
      increased with the days of spontaneous contraction. Western blot analysis of
      micro-dissected ES cell derived cardiac myocytes confirmed that TI-4
      immunostaining at early developmental time points represented ssTnI, and not the
      fast skeletal TnI isoform. We conclude that ES cell-derived cardiac myocytes
      display the developmental induction of cardiac TnI expression characteristic of
      vertebrate cardiac development. Thus, this model should be useful for studying
      the regulation and functional significance of TnI isoform expression during in
      vitro cardiogenesis.

PMID- 9019245
TI  - Selective regulation of cardiomyocyte gene expression and cardiac morphogenesis
      by retinoic acid.
AB  - Early heart development is known to be sensitive to retinoid concentrations; a
      specific pattern of malformations is observed in both vitamin A-deficiency and
      retinoid-toxicity states. While the influence of retinoids on early cardiac
      morphogenesis has been described previously, the effect of retinoids upon
      cardiomyocyte differentiation and gene expression is largely uncharacterized. We
      have established an in ovo chick embryo model in which slow-release retinoic acid
      (RA) induces four distinct cardiac malformations in a dose-dependent fashion.
      Late primitive streak-stage chick embryos were treated with all-trans-retinoic
      acid released from anion exchange beads placed on the embryo's left side and then
      allowed to develop further for 20-24 hr. At low doses (10 and 25 micrograms/ml
      RA) an abnormal loop structure was observed. At higher doses (50 and 100
      micrograms/ml RA) cardia bifida and clustered heart tissue were noted. Situs
      inversus only occurred after treatment with 100 micrograms/ml RA. RA-treated
      embryos were subsequently analyzed for appropriate cardiac myocyte
      differentiation using antibody staining and ELISA analysis to detect sarcomeric
      myosin heavy chain, tropomyosin, titin, and alpha-actinin protein expression.
      Alpha-actinin expression was significantly decreased in RA-treated embryos, as
      compared to DMSO-treated controls. Also, heart contraction rate was depressed
      after RA exposure. RA exposure did not alter the protein expression levels of
      sarcomeric myosin heavy chain or tropomyosin. The observed alterations are
      consistent with suggestions that retinoids may affect both morphogenesis and
      myofibril formation in the developing heart.

PMID- 9019246
TI  - Temporal expression of types XII and XIV collagen mRNA and protein during avian
      corneal development.
AB  - Using immunohistochemistry and competitive PCR for collagen types XII and XIV, we
      have followed the expression of these fibril-associated molecules during
      development of the avian cornea. By immunofluorescence histochemistry, both
      molecules are found in the acellular primary stroma and are therefore presumably
      of epithelial origin. During formation and development of the secondary corneal
      stroma, which is populated by mesenchymal cells, the molecules generally appear
      to be spatially segregated from each other. Type XIV collagen is found throughout
      most of the stroma, and therefore is predominantly a product of stromal
      fibroblasts. During subsequent compaction of the cornea, an event necessary for
      corneal transparency, the collagen XIV mRNA level increases dramatically,
      suggesting that this molecule may play a role in this event. Type XII collagen is
      more localized, occurring mainly in regions of the secondary stroma where
      matrices interface, such as where Bowman's membrane and Descemet's membrane abut
      the orthogonally layered collagen fibrils of the stromal matrix. These
      interfacial regions are highly stable areas of the cornea as determined
      previously by protease digestion and thermal denaturation studies. Type XII
      collagen may be involved in this stabilization.

PMID- 9019247
TI  - Polarizing activity, Sonic hedgehog, and tooth development in embryonic and
      postnatal mouse.
AB  - Tooth development involves reciprocal epithelial-mesenchymal interactions,
      polarized growth, mesenchyme condensation, and complex morphogenetic events.
      Because these processes bear similarities to those occurring in the developing
      limb, we asked whether morphogenetic signals found in the limb also occur in the
      developing tooth. We grafted mouse embryo tooth germs to the anterior margin of
      host chick embryo wing buds and determined whether the dental tissues had
      polarizing activity. Indeed, the grafts induced supernumerary digits. Activity of
      both molar and incisor tooth germs increased from bud to cap stages and was
      maximal at late bell stage in newborn. With further development the polarizing
      activity began to decrease, became undetectable in adult molar mesenchyme but
      persisted in incisor mesenchyme, correlating with the fact that incisors grow
      throughout postnatal life while molars do not. When different portions of
      neonatal incisors were assayed, a clear proximo-distal gradient of activity was
      apparent, with maximal activity restricted to the most proximal portion where
      undifferentiated mesenchyme and enamel organ reside. In situ hybridizations
      demonstrated that prior to induction of supernumerary digits, the tooth germ
      grafts induced expression in host tissue of Hoxd-12 and Hoxd-13. In addition,
      whole-mount in situ hybridizations and immunohistochemistry showed that
      developing tooth germs express Sonic hedgehog (Shh). Shh expression was first
      detected in bud stage tooth germs; at later stages Shh transcripts were prominent
      in enamel knot and differentiating ameloblasts at the cuspal region. We concluded
      that tooth germs possess polarizing activity and produce polarizing factors such
      as Shh. As in the limb, these factor(s) and activity probably play key roles in
      establishing polarity and regulating morphogenesis during early tooth
      development. Given its subsequent association with differentiating ameloblasts,
      Shh probably participates also in cytogenetic events during odontogenesis.

PMID- 9019249
TI  - Expression of neurotrophin receptors during rat tooth development is
      developmentally regulated, independent of innervation, and suggests functions in
      the regulation of morphogenesis and innervation.
AB  - Low-affinity neurotrophin receptor (LANR) and trk receptor tyrosine kinases
      (trks) serve as low- and high-affinity receptors for neurotrophins. Besides
      promoting the development and maintenance of the mammalian nervous system, it has
      been suggested that neurotrophins may have broader functions in the development
      of non-neuronal tissues. To evaluate the possible roles of neurotrophic factors
      in tooth development, we performed a detailed examination of the expression
      patterns of neurotrophin receptors during development of the rat tooth from
      initiation to completion of crown morphogenesis. mRNA expression was studied by
      in situ hybridisation and LANR protein was localised by immunohistochemistry.
      Furthermore, dissected tooth germs were cultured in vitro to examined the role of
      trigeminal innervation in the expression of neurotrophin receptors. mRNAs for
      LANR, trkB, and trkC, but not trkA, were detected in developing teeth. LANR and
      the truncated form of trkB, which lacks the intracellular tyrosine kinase domain,
      were expressed throughout tooth morphogenesis and their expression patterns were
      largely non-overlapping and changed spatio-temporally. trkC was expressed after
      birth, and it was restricted to dental papilla mesenchyme. The expression of all
      receptors correlated with the development of innervation, but, in addition, the
      expression of LANR and trkB appeared to be associated with cell differentiation
      and epithelial-mesenchymal interactions. The patterns of LANR, trkB, and trkC in
      teeth which underwent morphogenesis in organ culture were similar to those in
      vivo, which indicates that the expression of these neurotrophin receptors is not
      regulated by and does not depend on trigeminal innervation. The data suggest that
      neurotrophin receptors have roles in the development of tooth innervation, but
      that they also have non-neuronal, organogenetic functions.

PMID- 9019250
TI  - [Why public health research?].
AB  - In a state of the art paper a four step approach is made in order to investigate
      the question why public health research is necessary at all. 1. Expectations
      concerning public health research: The classical topics of public health research
      will continue to be relevant. Additionally, health promotion especially for low
      income and other risk groups should become important. For this purpose public
      health should try to relate to politics. Considering available resources and the
      quality of services goals should be determined as regulative criterias for the
      health system. Public health research will only remain relevant in the future if
      it turns from the traditional approach of public health medicine to what is
      called the new public health paradigm and if it adds the system approach to the
      population approach. 2. Target groups of public health research are policy makers
      and institutions as well as persons in the health care system. It has to be
      checked if these target groups are reached. Policy impact is more important than
      science impact. 3. Expectations to public health research concern the transfer of
      public health into other areas of science, the establishment of new institutions
      and teaching programmes and its inter-disciplinarity. Deficits exist in the
      selection of relevant topics and in the innovative power of projects. 4.
      Proposals for further public health actions refer to politically dominant issues
      which are to be defined by consensus conferences.

PMID- 9019248
TI  - Specific teratogenic effects of different retinoic acid isomers and analogs in
      the developing anterior central nervous system of zebrafish.
AB  - Vertebrate embryos are sensitive to retinoic acid, either in deficiency or in
      excess. Although all-trans retinoic acid (RA) and 9-cis RA are known to have
      distinct but overlapping activities in higher organisms, only the all-trans
      isomer has been investigated in detail as a teratogen in zebrafish. We have
      identified profound and specific effects of 9-cis RA when administered to
      zebrafish embryos, and have confirmed the results of prior studies on the
      teratogenic effects of exogenous all-trans RA. Moreover, we have identified a 1
      hr period during gastrulation in which embryos are particularly sensitive to the
      teratogenic effects of RA. In the course of these investigations, we have also
      studied the effects of two synthetic retinoids-a 9-cis RA analog, SR11217, and an
      all-trans RA analog, TTAB. An application of all-trans RA to the early zebrafish
      gastrula leads to defects that are limited to the caudal midbrain and rostral
      hindbrain. Our experiments show that an application of exogenous 9-cis RA for a
      period as short as 1 hr and at a concentration as low as 0.1 mu M can block
      differentiation of the rostral CNS. We have observed abnormal phenotypes using
      DIC optics, and have demonstrated further abnormalities using whole-mount
      immunocytochemical staining with antibodies to HNK-1 and acetylated alpha
      tubulin. Major axon tract formation in the anterior CNS is unambiguously
      disrupted by the administration of 9-cis RA but not all-trans RA. Furthermore,
      exogenous 9-cis RA produces a qualitative alteration in the multiple-site
      expression pattern of the hlx-1 gene within the rostral CNS, while treatment with
      all-trans RA leads only to a weakened expression signal. The administration of
      TTAB and SR11217 result in distinctive inhibitions of hlx-1 expression. Unlike
      all-trans RA, which causes premature par-2 expression in the posterior midbrains
      of a majority of embryos, 9-cis RA leads to a complete deletion of this domain
      throughout development. These results suggest that 9-cis RA is a more active
      teratogen than all-trans RA in rostral CNS structures of the zebrafish embryo.

PMID- 9019251
TI  - [Rendering public health reports in cities and regions--results of a model trial
      in Brandenburg and North Rhine-Westphalia].
AB  - The purpose of health reporting is to give orienting advices for health policy at
      regional and local level. In fact, there are only few communities and districts
      engaged in health reporting. A pilot project run in North Rhine-Westphalia and
      Brandenburg tried to fill the gap by developing and examining methods and
      procedures of producing regional health reports. Therefore a system of report
      topics was drawn up which allowed gradual processing and division of work between
      the five participating local health departments. Each health department chose
      three topics to be dealt with during a two-year phase of practice. Those working
      on the project individually advised and supported planning and realisation of the
      reports. The "health reporter" in the local health department should organize the
      production of the reports together with experts. Because of lack of experience or
      fear of not being accepted in an organizing role this person mainly functioned as
      author of the report. This had a negative effect on quality and continuity of the
      work. It can however be regarded as a success of the pilote scheme that this
      development will be continued in form of a broader planned project supported by
      the Ministry of Employment, Health and Social Affaires of Northrhine-Westphalia.

PMID- 9019252
TI  - [Use of drugs by women in the federal Saxony district based on survey data].
AB  - This study examines sex-specific differences in drug use of the Saxon population
      and compares them with relevant studies in the old Federal States. This study is
      based on data of the Drug Survey East (1992) which were secondary analyzed for
      Saxony. The sample population was representative for Saxon inhabitants aged 18-79
      years and encompassed 765 participants interviewed by physicians about their drug
      use in the last 7 days. The drug exposure in women younger than 60 years is
      significantly higher than in men of the same age group. The difference can only
      partially be explained by the intake of oral contraceptives. Compared with men
      women take a higher number of different drugs and take more often self-acquired
      drugs in addition to the drugs prescribed by physicians. A comparison Saxony
      Bremen shows that the intake of hormonal contraceptives, antihypertensives and
      betablockers in Saxon women is much higher than in women in the old Federal
      States, thyroid therapeutics, however, are used less often. Possible reasons for
      sex-specific and regional particularities in drug use are discussed.

PMID- 9019253
TI  - [Counseling concepts and services of health-associated self-help initiatives].
AB  - Self-help groups formed increased since the beginning of the eighties; in the
      field of health especially chronically ill persons met to cope with their daily
      illness-related problems. As these self-help-initiatives developed into suppliers
      of services this study should provide information about the special quality of
      counselling concepts and other services. A telephone interview with 224 self-help
      initiatives revealed a high proportion of counselling activity (75%). Based on
      the concept of Grounded Theory a qualitative analysis shows that the perspectives
      "service provision" and "social support" examined separately so far can only be
      understood in their combination. Especially community narratives proved to be
      connecting structural elements on which counselling concepts are based. These
      community narratives were reconstructed from narrative patterns of stories,
      mottos, rituals and others. Further essential structural elements are the
      principle of mutuality, the collective search for a panacea, processes of
      empowerment and the reference to everday life and environment. The principle of
      self-help and empowerment is highly valued by the patients. To incorporate this
      principle in the health care system a closer cooperation of these two systems
      should be strived for. Therefore it is necessairy to develop a theory of self
      help specific counselling in combination with results from salutogenesis
      research.

PMID- 9019254
TI  - ["I never feel free"--women care for the demented husband, father or mother].
AB  - The care of elderly relatives with dementia is not any longer a job exclusively
      done by women nevertheless the care for three quarters of patients is mainly
      provided by women. This study comprises 70 persons consulting the "Alzheimer
      Advice Centre" in Leipzig. The aim was to examine the difference between nursing
      men and women with regard to the way they experience their situation. Independent
      of sex nursing persons experience their job as a strain. Especially spouses
      suffer from depressive disorders, states of exhaustion and pain in arms and legs.
      Nursing spouses differ in their ways of coping with regard to their sex. Wives
      experience the symptoms of dementia and the limitation of personal freedom as
      stressing whereas husbands pick out as a central theme the worries about their
      wives. Men use instrumental support in the nursing situation more often than
      wives. Altogether mainly women provide care. Sometimes they even take care of
      several persons. Therefore the resulting strains and limitations are to be
      regarded as special problems of women.

PMID- 9019255
TI  - [Ambulatory management of the psychiatrically disturbed elderly--a comparative
      empirical study of 2 health care regions].
AB  - Gerontopsychiatric centres are functional settings which provide mainly out
      patient care for mentally ill elderly persons. The centres were established in
      order to transfer the care of mentally ill elderly people from in-patient to out
      patient care. This study examines to which extent this goal can be reached and
      where the limits of this transfer are. Two regions, the city of Bielefeld without
      gerontopsychiatric centre and the Gutersloh district with such a centre, were
      compared. It was shown that a transfer from intramural to extramural care was
      successfully accomplished by gerontopsychiatric centres. The transfer is scarcely
      limited by kind and severity of the disorder. Often an informal network is
      necessary for an out out-patient or partially out-patient care. But also with
      weak networks out-patient care is possible if there is a good-functioning formal
      network. Gerontopsychiatric centres constitute a central structural element in
      community-oriented care of the mentally ill elderly. They can help to realize the
      goal of a self-determinant and independent life.

PMID- 9019256
TI  - [Evaluation of measures for improving patient management in diabetes].
AB  - In diabetes mellitus as a chronic disease the success of treatment depends
      largely on the patient's cooperation. Therefore, over the last ten years, a
      number of models for the improvement of diabetes care were developed in Germany.
      These models were described and evaluated in this study. Only measures focussed
      on structural and organizational features were included in the analysis. After
      identifying the 69 relevant methods, they were described in terms of structures,
      aims, target groups and results. In a second step, effectiveness, efficiency and
      generalizability of the models were analyzed. Some of the programs proved to be
      effective and should be implemented in the whole country. More attention should
      be paid to the prevention of complications. The strict separation between in
      patient and out-patient care should be eliminated. Patients should be informed
      about results of quality monitoring. In many models, no appropriate evaluation
      was carried out. Therefore, this study emphasized the importance of a thorough
      evaluation of future models for the improvement of diabetes care. Instruments for
      evaluation should be determined already when the intervention is being planned.

PMID- 9019257
TI  - [Quality of diabetes management in the free Saxony state--scientific evaluation
      of the Saxony model for managing diabetes. EVA group].
AB  - After the societal change in the "New Federal States" of Germany Saxon
      diabetologists developed an integrated concept for care of diabetic patients: the
      Saxon Care Model (SCM). It aims at quality assurance in diabetes care and is
      based on services by cooperating general practitioners and specialists. This
      model was evaluated. First results were obtained describing the quality of care
      for 510 patients at baseline. This sample was collected at two specialized
      diabetologists (level 2), two specialized out-patient units at universities
      (level 2) and two general practitioners (level 1). The design of the study is a
      descriptive evaluation. Process and outcome quality at specialized and primary
      care units working according to the SCM is relatively high. HbA1c measurements
      were taken in order to quantify outcome quality. The results for primary as well
      as specialized care units ranged from acceptable to very good. They unfortunately
      cannot be generalized. The patients expressed that their quality of life was
      limited only scarcely. The presented preliminary results indicate a high
      effectiveness of the SCM with regard to relevant process-related outcome
      variables. The large variance between single practices of both levels
      demonstrates that deficits in early diagnosis of diabetes-related complications
      still exist. On the other hand this points towards resources of quality
      improvement. The influence of quality assuring measures, e.g. quality circles,
      will be assessed in a three-year follow up.

PMID- 9019258
TI  - [Comprehensive life style changes by coronary patients--an intervention study].
AB  - In an intervention trial 31 coronary patients participated in a comprehensive
      lifestyle change program and 43 control patients received the usual care of the
      conventional cardiac rehabilitation system. First preliminary findings show that
      the patients in the intervention group not only improved their health related
      lifestyle but also increased their exercise capacity and reduced depression,
      while there was no substantial improvement in the control group. Up to the
      present, the existing data indicate that German heart patients are able to make
      comprehensive lifestyle changes and that these changes have positive effects on
      biomedical and psychosocial variables.

PMID- 9019259
TI  - [Health promotion in the work environment--old and new challenges for public
      health].
AB  - Associations between work and health can be found at many different levels. Work
      itself can have health hazardous as well as health promoting effects. Work
      defines status and life-style as well as social security and occupies a large
      proportion of time in our lives. Until now the process to integrate issues of
      worksite prevention and health promotion into Public Health proceeds slowly in
      contrast to other countries e.g. the USA. Weak connections between occupational
      medicine and Public Health as well as relative few projects focussing on work
      site in the Public Health Research Associations reflect this trend. Work site
      public health research according to the guidelines of the Ottawa Charta (WHO)
      could enhance the transition of approaches justified now in terms of risk and
      legal liability towards an orientation on health resources and preventive
      potentials. This transition is promising in regard to the science of public
      health. However, bottleneck facilities can be identified: the development of
      appropriate health reports in companies, the implementation and further
      development of new steering models for worksite interventions (especially the
      organizational development) and the implementation and further development of
      appropriate form of quality assurance which can be evaluated.

PMID- 9019260
TI  - George W. Huntley: Cortical Explorer Award.

PMID- 9019261
TI  - Randall R. Johnson: Cortical Scholar Award.

PMID- 9019263
TI  - [Total vascular exclusion in liver surgery].
AB  - II cases of major hepatic resections under total vascular isolation (TVA) are
      presented: 4 women and 7 men, age between 17 and 70 years (mean 39.6 years). In
      another 2 cases the method was abandoned because the patients did not tolerate
      the vena cava clamping. The main indication for TVA were large tumors located
      near the suprahepatic veins opening into the vena cava. The diagnosis in the 11
      cases was: hepatocellular carcinoma--3 cases, cholangiocarcinoma--1 case, colo
      rectal metastasis--1 case, hemangioma--3 cases, hamartoma--2 cases, diffuse
      suppuration of the right lobe--1 case. The warm ischemia time was between 25 and
      50 min (mean: 36.8 min). There were no intraoperative complications. The mean
      quantity of transfused blood was 450 ml. Postoperatively two patients bled and
      were reoperated. Both subsequently developed liver failure and died and in both
      cases microscopy found histologic lesions of chronic hepatitis. The mortality was
      then 18.1%. Six patients (54.5%) developed postoperative complications. Worth
      noting are 2 cases of transient liver failure, both in patients with cancer. The
      ICU stay was between 2 and 14 days (mean 7.1) and the whole postoperative
      hospitalization was between 11 and 46 days (mean: 16).

PMID- 9019262
TI  - [Mechanical digestive system suturing devices].
AB  - Between 1994 (December)-1996 (May) 150 patients have been operated on using one
      or many stapling devices. The staplers disposable to us were the "Linear Cutter"
      or GIA (Gastrointestinal Anastomosis), "Linear Stapler" (TA) and "Intraluminal
      Circular Stapler" or EEA (end-to-end anastomosis) types, produced by ETHICON
      (Johnson and Johnson Ltd. Company). The principles operations performed were
      various digestive resections, intervisceralis anastomosis and interventions of
      reconstructions (in oesophagus surgery, ileal pouch etc.). The advantages of
      staplers applications are: a) the reduction of the time of operation, of the
      anesthesia, of the blood loss; b) a soft manipulation of the tissues; c) a
      smaller inflammatory reaction and the prevention of intraoperative septic
      contamination and d) a better and faster take back of the functionality of the
      anastomosis. There were only 4 intraoperative haemorrhages easy controllable.
      Postoperative complications: a) 3 haemorrhages medically treated; b) immediate
      leakage 1 patient after colorectoanastomosis, treated by Hartman colostomy;
      precocious, 7 patients and after 4-6 month, 2 patients. Corrective iterative
      interventions were necessary only in 5 patients. The operative mortality-1
      patient, the cause of death being a bronhopneumonia after a radical
      oesophagectomy with oesophagoplasty (oesophageal cancer). There was not
      postoperative mortality depending of stapling application. We don't observed late
      postoperative complications like stenosis of various anastomosis, quoted in the
      literature, because the time of following of our 150 patients is too short
      (maximum 18 months). The conclusions are that the stapling devices are a real
      surgical progress with the conditions of a correct indication and adequate
      tactics and operative technique. The economical effort is justified and entirely
      compensated by the major benefits obtained for the patients.

PMID- 9019264
TI  - [Surgical prosthesis in Klatskin's tumor: the indications and results].
AB  - The unresectable Klatskin tumors can benefit from surgical polliction through
      intrahepatic biliodigestive anastomosis or surgical stenting (lost tube, "U" tube
      Terblanche or "T" tube). 85 Klatskin tumors were operated in 20 years in the
      Surgery Clinic "Colentina" and in the Surgery Clinic "Interdepartamental".
      Surgical stenting was performed in 13 cases. The operation is very easy, from the
      technical point of view++, and the results are better composed to retrograde
      endoscopical prosthesis and transparietohepatic prosthesis. Stenting has a much
      lower morbidity and mortality than the intrahepatic biliodigestive derivations.
      If offers an acceptable life comfort for the surviving period.

PMID- 9019265
TI  - [The laparoscopic treatment of varicocele--a technical note].
AB  - After a short exposure of the main clinical and anatomical aspects of the
      varicocele, as arguments for a wider surgical indication, the authors present the
      technique of laparoscopic varicocelectomy. The operation implies general
      anesthesia and may be performed by transperitoneal or properitoneal approach-
      similar to laparoscopic hernia repair. The main step is the dissection, clipping
      or bipolar coagulation and section of the varicose spermatic veins.

PMID- 9019266
TI  - [Cancer of the head of the pancreas with a unique evolution].
AB  - Case report of a 67-years-old man with cephalopancreatic carcinoma and a peculiar
      evolution, undergoing several operations. The diagnostic was established 3 years
      ago through a peroperative pancreatic bioptic puncture, followed by
      choledochoduodenostomy considering the tumor as inextirpable. After 2 1/2 years
      symptoms of high occlusion and upper digestive bleeding caused by duodenal
      invasion and a Wolfler precolic gastrojejunostomy was performed. After 4 month
      the upper digestive bleeding relapsed severely imposing the second reintervention
      (cephalic duodenopancreatectomy with a special montage). The evolution was
      favourable, the clinical, biological and imagistic control at 6 month showing the
      absence of recidive.

PMID- 9019267
TI  - [Esophageal stenosis and esophagotracheal fistula with concomitant gastric ulcer
      in "caustic soda" ingestion].
AB  - The article deals with a special case through it's gravity and lesional
      complexity. A forty years old ill person with esophagus stenosis and postcaustic
      esophagotracheal fistula, having both a gastric ulcer on the date of surgery is
      operated in three stages: 1. Vagotomy, pyloroplasty and gastrotomy. 2.
      Esophagectomy with Kirschner-Nakayama gastric grafting. Posterior tracheorraphy
      with esophageal muscular patch. 3. Anastomotic cervical stenosis--plastic
      replacement (grafting) with a fat-less skin.

PMID- 9019268
TI  - [The etiopathogenetic and therapeutic correlations in chronic lymphocytic
      gastritis].
AB  - Haot et. al. (1,2) described in 1985 a new histopathologic entity, the
      lymphocytic gastritis, characterised by large number of intraepithelial T cells.
      The condition is usually symptomatic and related to an endoscopic form of
      gastropathy; it has an easily recognizable histology. According to The Sydney
      System it is classified as a special form (3); no etiopathogenic relation is
      established. The clinical significance and treatment are currently unclear (4).
      In one case, affected by peripheric T cell disfunction, there was significant
      clinical, endoscopic and histologic improvement after vagotomy, hemigastrectomy
      and total duodenal diversion. The possible favorable effect of surgery on
      lymphocytic gastritis, a diffuse gastric pathology, is discussed. To our
      knowledge this has not been reported before.

PMID- 9019269
TI  - [An experimental model of the microsurgical cannulation of the thoracic duct in
      the rat].

PMID- 9019270
TI  - [The paraclinical diagnosis of hemoperitoneum].

PMID- 9019271
TI  - [Palliative total gastrectomy].
AB  - Gastric cancer, because of lymphonodulary and local extension, often allows only
      palliative surgery. This study tries to present the total gastrectomy as an
      alternative meant to improve the life of the patients who cannot hope to radical
      cure. Thirty-one patients were submitted to this operation during the last five
      years. The main indication for surgery was cancer extended to the gastric corpus,
      mainly on the posterior aspects and almost reaching the cardia. Because of
      lymphonodulary invasion over N2, hepatic and pancreatic and colonic invasion over
      N2, hepatic and pancreatic and colonic invasion and because of the metastases,
      the resections were palliative. The operations consisted of total gastrectomy and
      omentectomy, without trying to reach lymphatic stations over NI. All cases
      presented evidence of restant cancerous tissue involving the pancreas, the liver
      or the other lymphatic stations, but the main purpose was the ablation of the
      gastric tumor. Postoperatively we recorded 3 deaths, 9 anastomotic fistulae and
      an average survival of 9 months (6-13 months).

PMID- 9019272
TI  - Scanning electron microscopy of C-banding.
AB  - The mechanism of C-banding was analyzed on the basis of the structural changes of
      the 30 nm chromatin fibre using scanning electron microscopy (SEM). SEM of non
      banded metaphase spreads of L-cells revealed chromosomes consisting of 30 nm
      chromatin fibre loops along the entire length. No marked difference in both the
      dimension and appearance of such looped structures was discernible between the
      centromeric region and the rest of the chromosome. In contrast, C-banded
      chromosomes exhibited a conspicuous alteration of the fibre conformation in the
      centromeric region. The looped, fibrous structures were almost completely lost
      from this region, while the non-centromeric region still exhibited fibrous
      structures with slightly different appearances compared with those observed in
      the control chromosomes. On the other hand, results obtained using fluorescence
      microscopy showed that more DNA retained in the centromeric region than in the
      non-centromeric region. Since the analytical experiments exhibited that the
      characteristic collapsed state of the centromeric region occurred only with the
      alkali treatment but neither with the 2 x SSC nor acid treatments, the
      centromeric heterochromatin seemed to contain some specific protein which should
      be sensitive to alkali. The structurally collapsed but subsequently compact
      centromeric region may become more, or still, resistant to the DNA extraction due
      to the 2 x SSC treatment and the centromeric chromatin thus retained may be
      visualized as the C-band.

PMID- 9019273
TI  - Characterization of F-actin bundling activity of Tetrahymena elongation factor 1
      alpha investigated with rabbit skeletal muscle actin.
AB  - Elongation factor 1 alpha (EF-1 alpha) is an essential factor for protein
      synthesis in eukaryotes. Here, we demonstrated that Tetrahymena EF-1 alpha
      induced bundles of rabbit skeletal muscle F-actin as well as Tetrahymena F-actin
      in vitro, although Tetrahymena and skeletal muscle actins are different in some
      parts of their primary structures and in the binding abilities to some actin
      binding proteins. Co-sedimentation experiments showed that the binding ratio of
      Tetrahymena EF-1 alpha to skeletal muscle F-actin in the bundles was 1 : 1.
      Electron microscopic observation showed that alkaline pH or high ionic strength
      reduced the bundling activity of Tetrahymena EF-1 alpha to some extent, although
      the EF-1 alpha seemed to be able to induce bundling of the F-actin within the
      range of physiological condition.

PMID- 9019274
TI  - Effects of inhibin on rat gonadal differentiation and development in vitro.
AB  - Previously we examined that inhibin-alpha subunit, transforming growth factor
      beta 1 (TGF-beta 1) and epidermal growth factor (EGF) were expressed in sex-,
      cell- and stage-specific manners in perinatal rat gonads. To clarify effects of
      these growth factors on the rat gonadal differentiation and development,
      indifferent gonadal primordia with mesonephric tubules on gestational day 13 were
      cultured in vitro for 4 days in serum-free CMRL-1066 medium with inhibin, TGF
      beta 1, EGF, anti-sera against these growth factors, testosterone or estradiol-17
      beta, and then morphologically examined with reference to seminiferous tubule
      formation, germ cell division, Wolffian and Mullerian duct development. In male
      gonads, anti-inhibin-alpha serum suppressed the seminiferous tubule formation but
      inhibin, TGF-beta 1, EGF or steroid hormones did not affect on the tubule
      formation, germ cell proliferation nor gonoduct development. Seminiferous tubules
      in male gonads cultured in the medium containing anti-inhibin-alpha serum were
      incomplete and irregular in shape. On the other hand, in female gonads, inhibin
      suppressed the germ cell division and anti-inhibin-alpha serum led to the
      necrosis of germ cells, but other factors affected to neither sex cord formation
      nor germ cell division. Testosterone and estradiol-17 beta stimulated female
      Wolffian and Mullerian duct development, respectively. These results indicate
      that inhibin induces the seminiferous tubule formation and suppresses the female
      germ cell division in developing rat gonads in vitro.

PMID- 9019275
TI  - New Orleans 7th International Symposium on Antiphospholipid Antibodies.
      Proceedings and abstracts.

PMID- 9019276
TI  - [Role of modulation in biological effects of electromagnetic radiation].
AB  - Data, describing a role of modulation of electromagnetic fields in development of
      biological effect, are considered. Outcomes of researches, indicating the
      dependence of a response of nervous and immune systems on a kind of modulation at
      low levels of effect, are represented. The necessity of the account of a role of
      modulation in an evaluation of electromagnetic danger is formulated.

PMID- 9019277
TI  - [Characteristics of microwave and thermal heating of samples of cell suspensions
      and solutions of several compounds].
AB  - The influence of microwaves and heat on dynamics of heating of samples of intact
      and inactivated bacteria Escherichia coli and solutions of some basic molecular
      components of cell was investigated. It was shown that microwaves induce
      different dynamics of heating of all samples. On the contrary, thermal action
      induces identical dynamics of heating of all this samples except vegetable oil
      which was heated more intensively.

PMID- 9019278
TI  - [Effects of unmodulated electromagnetic radiation of decimetric diapason on the
      morphogenesis of Drosophila].
AB  - Microwave effects on drosophila morphogenesis were studied. Drosophila embryo
      were exposed by continuous wave 460 MHz at SAR = 1-5 Wt/kg. It was found that
      irradiation induced some morphosis such as imago legs and wings form alterations.
      These effects depended on embryo age, SAR and period exposure. It was proposed
      that the local microwave heating is responsible for describe effects.

PMID- 9019279
TI  - [Effects of electromagnetic radiation of various modes on heart activity (in
      experiments)].
AB  - On spinal cord frogs and isolated interauricle to a partition of heart in vivo
      and in vitro influence the MICROWAVES of a radiation in continuous and modulated
      modes on function of heart (9.3 Hz is investigated; 0.348-0.16 and 0.016 mV/sm2,
      modulation from 1 up to 100 Hz). A possibility of influence of an electromagnetic
      exposure on heart frequency and rhythm is revealed. Pointing of heart in vitro by
      a neutral red resulted in large number of % of experience in a stop of irradiated
      heart.

PMID- 9019280
TI  - [Effects of 2375 MHz pulse-modulated microwave radiation on ATPase activity of
      the rat muscle actomyosin].
AB  - Solution of rat muscle actomyosin (AM) was exposed to pulse-modulated microwave.
      Carried frequency was 2375 MHz. The rectangular pulse modulation was in the range
      of 50-300 pulses per second. It was shown that AM activity was dependent both on
      modulation frequency as well as on microwave intensity. It was shown the
      frequencies of modulation which were changed ATP-ase activity of AM.

PMID- 9019281
TI  - [Dependence of changes in summary bioelectric activity of the brain on low
      intensity microwave irradiation from density of flow energy].
AB  - In present experimental research has found the confirmation the opinion existing
      in literature about absence of direct proportional dependence effects of low
      intensity microwave from density of flow of energy. Work submits the analysis
      electroencephalograms various areas of the cortex brain of rabbits on 6 GHz
      microwave irradiation with energy 0.03-0.40 MW/sm2.

PMID- 9019282
TI  - [Experimental data on reaction of neurons of the brain to low-intensity package
      pulsing microwave irradiation].
AB  - In experiments on non-movement rabbits with help specially made from organic
      glass of micromanipulator and non-artefactions electrodes and wires study the
      bioelectrical activity separate neurons on moment of package-pulsing microwaves
      irradiation (1.5 GHz, duration of pulse-0.4 ms, frequency their recurrences 1000
      Hz, duration of packs-16 ms, frequency their recurrences-0.12 Hz, energy-0.3
      mW/sm2). The results of experiments are compared with control series, where is
      carried out false irradiation.

PMID- 9019283
TI  - [Effects of a permanent magnetic field on 45Ca2+ ion influx in excitable and
      inexcitable cells and proliferative activity of rat spleen cells].
AB  - When experimental animals were exposed to Permanent Magnetic Fields with magnetic
      induction (B = 0.2 T), the influx of 45Ca2+ ions into brain cells was activated,
      but the influx of 45Ca2+ ions into spleen cells was depressed. Similar effect was
      observed upon incubation of brain and spleen tissues in magnetized physiological
      solution. Incorporation of 3H-thymidine into spleen cells increased upon direct
      exposition to magnetic field and upon exposition of the spleen in magnetized
      physiological solution as well.

PMID- 9019284
TI  - [Effects of low-intensity electromagnetic radiation of extremely high frequency
      on the animal body within the framework of total low-dose x-ray irradiation].
AB  - Effect of low-intensive electromagnetic radiation of extremely high frequency
      (EMR EHF) on the rats, subjected to the low-dose X-ray irradiation (6.192 mC/rg)
      was investigated. Content of glial fibrillary acidic protein as well as glucose
      content and activity of glutamate dehydrogenase and malate dehydrogenase was
      studied. It was shown than EMR EHF modifies the X-ray irradiation effect:
      filament GFAP concentration in brain and glucose content in serum were restored.
      The authors suggest central nervous system participation in realization of EMR
      EHF effects on the organism.

PMID- 9019286
TI  - [Radiation protective effects of laser irradiation with wavelength 532 nm].
AB  - The combined effect of 532 nm laser radiation and alpha-particles on survival of
      Escherichia coli (AB 1157) has been investigated. The sensitivity of cells to
      alpha-particles was decreased by pre- and post-irradiation with laser.

PMID- 9019285
TI  - [Effects of a synthetic carbon-mineral sorbent and antibiotics on the development
      of combined radiation and thermal injury].
AB  - Male Wistar rats exposed to whole-body irradiation, the midline absorbed dose was
      7.5 Gy. Full-sickness thermal burn 15% of body surface inflicted immediately
      after irradiation. Experimental study of the therapeutic efficacy of
      enterosorption alone or in combination with antibiotics doxycycline and
      ciprofloxacin performed. The strong decrease of bacterial endotoxemia, toxic
      oligopeptides' level and general blood toxicity revealed after treatment compared
      with non-treated animals with combined injuries. Corrections of postirradiation
      intestinal dysbacteriosis revealed too. The best result observed when carbon
      mineral sorbent and antibiotics administered daily within the first 10-14 days
      after combined injury. Survival of treated animals increased up to 80% (all rats
      of control group died during 30 days after combined injury).

PMID- 9019287
TI  - [Characteristics of conditions of exposure of personal computers personnel
      (results of measurements, evaluation of hazards and methods of protection)].

PMID- 9019288
TI  - [Assessment of hazards of an electromagnetic field generated by the monitor (a
      study of conditions of short-term work of a personal computer operator)].

PMID- 9019289
TI  - [Exposure levels of persons involved in cleaning-up after the Chernobyl AES
      accident and included in the Russian State Medical and Dosimetric Registry].
AB  - Theoretical and practical problems related to the dosimetric data verification
      for recovery workers at the Chernobyl NBB are considered. Approaches and
      conclusions presented in the paper of L.A. Ilyin at al, (1). By using probability
      theory it was clearly that the method of dose verification developed in the
      reviewed paper and based on delta-entropy of statistical distribution failed to
      be scientifically founded. It does not permit to prove the existence of non
      random component in random sampling without additional assumptions. The main
      conclusion of the reviewed paper, that 60% of individual doses included in the
      all-russia state medical and dosimetric state registry (ARMDSR) differ from the
      real exposure doses, is analysed and quantitatively estimated for several group
      of recovery workers. Our results present evidence that ARMDSR data do not contain
      a considerable part of "distorted" values even if the above mentioned method to
      take as valid.

PMID- 9019290
TI  - Operative vs. nonoperative treatment of intra-articular fractures of the
      calcaneus: a prospective randomized trial.

PMID- 9019291
TI  - Proceedings of the International Symposium on Chromatography, on the occasion of
      the 35th anniversary of the research group on liquid chromatography in Japan.
      Yokohama, Japan, 22-25 January 1995.

PMID- 9019292
TI  - Use of 3-(1,8-naphthalimido)propyl-modified silyl silica gel as a stationary
      phase for the high-performance liquid chromatographic separation of purine
      derivatives.
AB  - The use of a packing material, 3-(1,8-naphthalimido)propyl-modified silyl silica
      gel (NAIP), as a stationary phase for high-performance liquid chromatography, has
      been studied. NAIP behaved like a reversed-phase stationary phase with some pi-pi
      interaction. Purine derivatives, i.e., xanthine, hypoxanthine, uric acid,
      theobromine, theophylline and caffeine, were separated by a column packed with
      NAIP using an eluent of borate solution (pH 6.4)-MeOH (50:50, v/v). Of these,
      caffeine was selected as the target of the subsequent investigation and its
      determination was examined in commercially available medicinal drinks and
      pharmaceutical preparations. The average recoveries of caffeine were 98.0-107.4%
      for five drinks and 99.6-107.8% for five tablets and one powder. Subsequently,
      determination of caffeine and its metabolites in human plasma was examined. In
      twelve normal human plasma, caffeine levels ranged from 0.24 to 4.26
      micrograms/ml. Time curves of plasma caffeine concentrations and those of its
      demethylated metabolite, 1,7-dimethylxanthine (1,7-DMX), after an oral ingestion
      of caffeine (200 mg) were measured by the proposed method and it was found that
      the maximum concentrations of caffeine and 1,7-DMX were obtained at 1-1.5 h and 3
      6 h after ingestion, respectively.

PMID- 9019293
TI  - Synthesis and characterization of polymer-coated mixed-functional stationary
      phases with several different hydrophobic groups for direct analysis of
      biological samples by liquid chromatography.
AB  - Three types of polymer-coated mixed-functional (PCMF) silica column-packing
      materials for the direct analysis of biological liquids have been synthesized.
      These packing materials all have polyoxyethylene groups as their hydrophilic part
      but differ in their hydrophobic part (methyl groups for Me-POE, phenyl groups for
      Ph-POE, and octyl groups for Oc-POE). Retention characteristics with respect to
      several drug molecules, and protein recovery, were studied for each of the three
      types with different amounts of hydrophobic groups attached. Of the PCMFs
      prepared, Oc-POE showed the greatest overall retention, and Me-POE displayed the
      greatest protein recovery.

PMID- 9019294
TI  - Applied slalom chromatography improved DNA separation by the use of columns
      developed for reversed-phase chromatography.
AB  - Improved resolution in slalom chromatography, a novel size-fractionation method
      discovered recently for relatively large DNA molecules (> 5 kpb), was obtained by
      using columns generally employed for reversed-phase chromatography: i.e., two
      types of Capcell-Pak (methyl or phenyl-derivatized 5-microns microbeads), and
      five types of Hypersil-3 packings (trimethylsilyl, dimethyloctyl, cyanopropyl,
      octadecyl or phenyl-derivatized 3-microns microbeads). The resolution of 5-15-kbp
      DNA was significantly improved by employing these columns, though the separation
      characteristics differed. When Capcell-Pak columns were used with a normal low
      salt eluting solvent (10 mM sodium phosphate, pH 6.8, 1 mM EDTA), chromatograms
      were obtained for lambda/HindIII fragments (a mixture of 0.1, 0.5, 2.0, 2.3, 4.4,
      6.6, 9.4 and 23.1-kbp fragments) similar to those obtained previously with
      Asahipak GS-310 5-microns size-exclusion packings. However, when up to 0.2 M NaCl
      was added to the solvent, the DNA was increasingly retarded, particularly the
      4.4, 6.6 and 9.4-kbp fragments, resulting in improved resolution in the low to
      middle molecular-mass range. The effect of salt was more significant with Capcell
      Pak Phe than C1, although various features characteristic of slalom
      chromatography were preserved with both columns; i.e., dependency on DNA size,
      flow-rate, and temperature. This suggests that a mixed mode of separation, that
      is, slalom mode and hydrophobic-interaction mode, was operating. Although all of
      the Hypersil-3 packings showed significant adsorption of lambda/HindIII fragments
      under low-salt conditions, the fragments could be eluted with satisfactory yield
      and resolution by adding acetonitrile (> 5%) to the solvent. Notably, these
      Hypersil-3 packings allowed resolution of a 4.4-kbp lambda/HindIII fragment from
      the flow-through fraction for the first time, possibly due to their small
      particle size. Thus, various packing materials developed for high-performance
      liquid chromatography proved to be applicable for slalom chromatography, though
      the eluting conditions still need to be refined. The results support the concept
      that slalom chromatography is based on a hydrodynamic phenomenon.

PMID- 9019295
TI  - Lectin-glycoenzyme column chromatography monitored by enzyme flow
      microcalorimetry.
AB  - A method based on the flow microcalorimetric determination of catalytic activity
      of immobilized enzyme in a so-called enzyme thermistor was used to monitor the
      process of lectin affinity chromatography of invertase on Concanavalin A-bead
      cellulose. The strong biospecific interaction between Concanavalin A and
      invertase was employed to determine the bound enzyme and this principle was used
      for the investigation of an alternative direct method for monitoring the lectin
      affinity chromatography of glycoenzymes. The results obtained by flow
      microcalorimetry showed that the catalytic activity of invertase immobilized on
      Concanavalin A-bead cellulose can be compared directly with the thermometric
      value delta Tmax. The validity of the method was also confirmed by the enzyme
      thermistor post-column method, which is based on the determination of the product
      from the immobilized invertase enzymatic reaction. The adsorption and desorption
      in the chromatography column were examined by flow microcalorimetry in small
      samples withdrawn from the column. Attention has been given to the operating
      parameters and the storage stability of the affinity sorbent. The binding ability
      of the affinity matrix decreased with the number of consecutive chromatographic
      runs, although its storage stability was satisfactory.

PMID- 9019296
TI  - Enantiomer separation by gas and high-performance liquid chromatography with
      tripeptide derivatives as chiral stationary phases.
AB  - Excellent enantiomer separation of a variety of racemic compounds, including
      alcohols, amines, amino alcohols, carboxylic acids, hydroxy acids and amino
      acids, was achieved by GC and HPLC with tripeptide derivatives, containing L
      valyl-L-valyl-L-valine isopropyl ester as a chiral selector, bonded to amino
      silicone oil (CSP-3) and N-(2-aminoethyl)-3-aminopropyl silica gel (CSP-4) via a
      triazine ring, respectively. These results show that the hydrogen bonding
      association between solutes and chiral stationary phases (CSPs) can play an
      important role in chiral recognition in both GC and HPLC. The joint use of two
      CSPs is promising for the direct separation of racemic compounds.

PMID- 9019297
TI  - Determining the characteristics of water pollutants by neural sensors and pattern
      recognition methods.
AB  - In this paper we have researched the influence of pollutants on such biological
      objects as photosynthesizing systems in order to reveal the capabilities and
      features of their application as the controlling sensor in integral ecological
      monitoring microsystems. It is proposed to elaborate upon the intelligent sensor
      on the basis of: (1) neural network technologies; (2) the possibility to separate
      the characteristics of the substances dissolved in water by means of the methods
      which recognize patterns in a functional space of the fluorescence curves; (3)
      the results of the chromatographic analysis of standard water samples. This
      sensor allows to predict water state and to make the optimal decisions for
      correcting an ecosystem's condition. The efficiency of such a system for water
      analysis can be improved using the dual measurement principle. This principle
      suggests identification of a biosensor model according to experimental data.

PMID- 9019298
TI  - Preparation and separation of hydroxy derivatives of uroporphyrinogen I by high
      performance liquid chromatography with electrochemical detection.
AB  - The preparation and high-performance liquid chromatography (HPLC) separation of
      meso-hydroxyuroporphyrinogen I, hydroxyacetic acid uroporphyrinogen I and beta
      hydroxypropionic acid uroporphyrinogen I is described. meso-Hydroxyuroporphyrin
      I, hydroxyacetic acid uroporphyrin I and beta-hydroxypropionic acid uroporphyrin
      I were isolated from the urine of a patient with congenital erythropoietic
      porphyria. The porphyrins were reduced to the corresponding porphyrinogens with
      3% (w/w) Na/Hg amalgam. The hydroxy porphyrinogens were separated on a Hypersil
      ODS column with 4% (v/v) acetonitrile in 1 M ammonium acetate buffer, pH 5.16,
      containing EDTA (0.27 mM) as the mobile phase, and detected electrochemically.
      Reduction of meso-hydroxyuroporphyrin I and hydroxyacetic acid uroporphyrin I,
      followed by HPLC analysis, showed that, in addition to the expected formation of
      meso-hydroxyuroporphyrinogen I and hydroxyacetic uroporphyrinogen I,
      respectively, uroporphyrinogen I was also produced. Reduction of beta
      hydroxypropionic acid uroporphyrin I, however, gave beta-hydroxypropionic acid
      uroporphyrinogen I, acrylic acid uroporphyrinogen I and uroporphyrinogen I as the
      products. The peaks were identified by conversion into the porphyrin methyl
      esters and analysed by liquid secondary-ion mass spectrometry.

PMID- 9019299
TI  - On-line high-performance liquid chromatographic-electrospray ionization mass
      spectrometric method for the study of tamoxifen metabolism.
AB  - An on-line high-performance liquid chromatographic (HPLC)-electrospray ionization
      mass spectrometric (ESI-MS) method has been developed and optimized for the study
      of tamoxifen metabolism. Metabolism in mouse liver microsomes was chosen to
      demonstrate the applicability and superiority of the method, since mice
      metabolize tamoxifen faster and produce more metabolites than rats or humans.
      Mouse liver microsomal preparations were incubated with tamoxifen in the presence
      of NADPH and MgCl2. The metabolites formed were separated and analyzed by the
      optimized HPLC-ESI-MS system. The separation was performed on a Res Elute-BD
      column (5 microns particle size, 250 x 4.6 mm I.D.) with 70% (v/v) methanol in
      0.5 M ammonium acetate as the mobile phase. A total of eleven metabolites have
      been detected, some of which have not been previously reported. The metabolites
      identified are: tamoxifen N-oxide, N-desmethyltamoxifen, 4-hydroxytamoxifen, 4'
      hydroxytamoxifen, 4-hydroxytamoxifen N-oxide, 4'-hydroxytamoxifen N-oxide, 4
      hydroxy-N-desmethylamoxifen, 4'-hydroxy-N-desmethyltamoxifen, 3,4
      dihydroxytamoxifen, 3,4-epoxytamoxifen and 3,4-epoxytamoxifen N-oxide.

PMID- 9019300
TI  - Quantitative structure-retention relationships in the examination of the
      topography of the binding site of antihistamine drugs on alpha 1-acid
      glycoprotein.
AB  - Quantitative relationships between the structure of antihistamine drugs (AHD) and
      their retention on an alpha 1-acid glycoprotein (AGP) HPLC column (QSRR) were
      studied in order to identify characteristic structural features of the binding
      site for AHD on AGP. The hydrophobicity of AHD was determined by HPLC on an
      immobilized artificial membrane (IAM) column. A highly significant QSRR equation
      was obtained which describes the retention of AHD on AGP in terms of the
      chromatographically determined hydrophobicity parameter, electron excess charge
      on the aliphatic nitrogen and a molecular size descriptor. The topography of the
      AHD-binding site on AGP was suggested to be a conical pocket with lipophilic
      regions at the mouth of the receptor and an anionic region close to the spike of
      the cone. Protonated aliphatic nitrogen is supposed to guide a drug molecule
      towards the anionic region of the binding site. Hydrophobic aryl moieties provide
      anchoring of the molecule in the lipophilic regions of the binding site. Steric
      hindrance prevents the molecule from plunging into the binding site.

PMID- 9019301
TI  - Simultaneous determination of alpha-tocopherol and alpha-tocopherolquinone by
      high-performance liquid chromatography and coulometric detection in the redox
      mode.
AB  - A simple, selective and highly sensitive assay method for the simultaneous
      determination of alpha-tocopherol and alpha-tocopherolquinone in plasma or
      erythrocyte membrane by high-performance liquid chromatography (HPLC) with a
      series of multiple coulometric working electrodes (CWE) was investigated. For
      good separation of alpha-tocopherol and alpha-tocopherolquinone, an MC MEDICAL
      C18 reversed-phase column and a mobile phase consisting of 96% methanol [methanol
      HPLC-grade distilled water (96:4, v/v)] with 40 mM sodium perchlorate were used.
      Also, selective, highly sensitive and simultaneous detection of these substances
      was performed in redox mode using a series of four CWE. In this detection mode,
      the first, second and third CWE were set at -0.45 V for pre-reaction and to
      prevent interference, the fourth CWE was used as an electrode for actual
      measurement with its potential set at +0.40 V against a palladium reference
      electrode. The detection limits were 50-100 pg. Excellent chromatograms of alpha
      tocopherol and alpha-tocopherolquinone were obtained within 8 min. The usefulness
      of reversed-phase HPLC with the redox detection mode was confirmed by application
      to the determination of the concentrations of alpha-tocopherol and alpha
      tocopherolquinone in a crude ethanol-hexane extract of rat plasma or erythrocyte
      membrane. These findings suggest that reversed-phase HPLC with the redox
      detection mode using a series of four CWE is applicable to study the preventive
      effect of alpha-tocopherol on lipid peroxidation.

PMID- 9019302
TI  - Highly sensitive and simple liquid chromatographic determination in plasma of B6
      vitamers, especially pyridoxal 5'-phosphate.
AB  - A simple and sensitive high-performance liquid chromatographic method for
      measuring the major vitamers of vitamin B6, i.e. pyridoxal and pyridoxal 5'
      phosphate (PLP), and 4-pyridoxic acid (4-PA) in plasma was developed. The
      vitamers and 4-PA from plasma were extracted with 0.8 mol/l perchloric acid. The
      separation by HPLC is accomplished using an ODS reversed-phase column and a
      mobile phase of 0.1 mol/l potassium dihydrogen phosphate containing 0.1 mol/l
      sodium perchlorate, 0.5 g/l sodium bisulfite adjusted to pH 3, at a flow-rate of
      1.0 ml/min. The vitamers and 4-PA were eluted within 13 min and their
      concentration is determined with a fluorometric detector (excitation, 300 nm;
      emission, 400 nm). In this method, PLP in plasma can be determined with high
      sensitivity using derivatization with sodium bisulfite in the mobile phase.

PMID- 9019303
TI  - Gas chromatographic amino acid profiling of wine samples for pattern recognition.
AB  - A rapid gas chromatographic profiling and screening method is described for the
      determination of free amino acids in wine samples. The amino acids in alkaline
      aqueous wines were allowed to react with isobutyl chloroformate. The resulting
      N(O,S)-isobutyloxycarbonyl amino acids were extracted by solid-phase extraction
      using Chromosorb P as the adsorbent and diethyl ether as the eluent after
      acidification, and then converted into stable tert.-butyldimethylsilyl
      derivatives with subsequent analysis by dual-capillary column gas chromatography
      and gas chromatography-mass spectrometry. Seventeen free amino acids were
      identified from the four wine brands studied. When the GC profiles were
      simplified to the corresponding amino acid retention index spectra in bar
      graphical form, they presented characteristic patterns for each wine brand.
      Stepwise discriminant analysis performed on the amino acid profiles provided star
      symbols characteristic of the wine brands.

PMID- 9019304
TI  - Determination of 5-aminolaevulinic acid dehydratase activity in erythrocytes and
      porphobilinogen in urine by micellar electrokinetic capillary chromatography.
AB  - A micellar electrokinetic capillary chromatographic (MECC) method has been
      developed and optimised for the separation of 5-aminolaevulinic acid (ALA) and
      porphobilinogen (PBG). The running buffer consisted of a mixture of 20 mM sodium
      phosphate and 20 mM sodium borate containing 50 mM sodium dodecyl sulphate (SDS)
      adjusted to pH 9.5 with 1 M NaOH. The running voltage and temperature were 20-25
      kV and 30 degrees C, respectively. The MECC method for the analysis of PBG is
      fast and simple and is useful for the screening of PBG in the urine of patients
      suspected to have acute intermittent porphyria (AIP), and for the confirmation of
      lead exposure by measuring red-cell ALA-dehydratase (ALA-D) activity with ALA as
      the enzyme substrate.

PMID- 9019305
TI  - Analysis of single-strand DNA conformation polymorphism by capillary
      electrophoresis.
AB  - Analysis of single-strand conformation polymorphism (SSCP) by capillary
      electrophoresis (CE) was developed. The conformational change of single-strand
      DNA is caused by a mutation in a DNA fragment. The change is detected as mobility
      shift in CE. The effects of acrylamide gel concentration, running temperature and
      fragment size amplified by the polymerase chain reaction (PCR) were studied to
      develop the separation of SSCP. The model DNA used was the divE 42 gene carrying
      wild- and mutant-type (G-->A point mutation at the 141 site). The results show
      that two single-strand DNA fragments that differ in one nucleotide can be
      separated by CE within minutes. This method was also applied to the separation of
      SSCP for N-ras gene including four kinds of mutations. All mutations tested in
      this study could be distinguished. CE is well suited for clinical analysis of
      SSCP because it is rapid and reproducible, allows on-line detection and is easy.

PMID- 9019306
TI  - Molecular recognition of phenobarbital in plasticizers equilibrium investigations
      on the solubility of the barbiturate artificial receptor and its binding to
      phenobarbital in plasticizers.
AB  - Environmental concern is renewing interest in selective, waste-free extractions.
      A recent report demonstrated an improved extraction of phenobarbital by means of
      a specifically designed molecular receptor. In that work, the solvent was CHCl3.
      The current work is the first step in extending extractions based on molecular
      recognition to reusable solvents, namely plasticizers. Phenobarbital
      aqueous/organic partition coefficients, receptor solubility, and phenobarbital
      receptor-formation constants in several plasticizers and in their CHCl3 solutions
      are reported. In addition, by a thermodynamic cycle, the free energy for transfer
      of the barbiturate-receptor complex from CHCl3 to plasticizers has been
      calculated. Finally, the data have been displayed in coordinate systems
      representing extraction efficiency and selectivity. The most selective extraction
      medium yielding useful extraction efficiency is dioctyl phthalate.

PMID- 9019307
TI  - [Advertising and tobacco].

PMID- 9019308
TI  - [Computed tomography and polymerase chain reaction in tuberculosis infection in
      childhood].
AB  - The recognition of children with tuberculous infection without disease is often
      difficult. Minimal active disease may be present in many cases but unrecognised
      on chest radiography or by microbiologic methods. We have performed computed
      tomography in 22 children with tuberculous infection, a normal chest radiograph
      and negative microbacterial culture. In 16 children we also performed DNA
      amplification by polymerase chain reaction in gastric aspirates. It was found
      that 14 of 22 (63%) infected children had enlarged lymph nodes. Adenopathies were
      more frequent in children less than 8 years-old and in the right paratracheal
      positions. Polymerase chain reaction was positive in 4 of 8 studied children with
      abnormal computed tomography and in none of the children with normal computed
      tomography. The demonstration of unrecognised active disease raises the question
      of the adequate treatment for the children with tuberculous infection. It is
      proposed that a two drug regimen would be more appropriate than isoniazid alone
      in children less than 8 years old.

PMID- 9019309
TI  - [Can we improve the prevention of tuberculosis? Analysis of the application of
      chemoprophylaxis].
AB  - To analyze the situations that make chemoprophylaxis for tuberculosis difficult.
      One hundred twenty-eight patients consecutive (106 HIV negative and 22 HIV
      positive) diagnosed of tuberculosis (TB) were studied. The patients were
      interviewed and a questionnaire was filled out in order to identify risk groups
      and determine what steps had been taken to prevent TB. In the HIV negative group,
      63 (57.8%) had at least one risk factor. The most common were contact with
      persons with active TB (31.1%), former TB (15.1%), rapid weight loss or chronic
      malnutrition (13.2%) and residence in closed institutions (5.6%). Of the 51
      (48.1%) for whom evaluation of chemoprophylaxis was indicated, 43 (84.3%) had
      been examined by a physician within the past five years; only 10 (23.3%) of them,
      however, had been checked for TB and isoniazide had been prescribed for only 4
      (9.3%). In the HIV positive group, 13 (72.2%) of those for whom evaluation of
      chemoprophylaxis was indicated had been seen by a physician; 12 (97.7%) of them
      were given tuberculin tests checked for TB and isoniazide was prescribed for 4
      (30.7%). None of the patients in either group who were prescribed a full course
      of prophylaxis actually took the drug enough. Most HIV negative patients for whom
      evaluation of chemoprophylaxis was indicated had been examined by a physician in
      the five years before disease was detected; less than a quarter of them were
      checked for TB, however. This situation is probably a consequence of the
      structure of health care in Spain as it affects TB control. Nearly all the HIV
      positive patients were checked for the disease, as they benefited from
      protocolized health care.

PMID- 9019310
TI  - [Drainage of loculated and/or multiloculated pleural effusions using a small
      caliber catheter and urokinase (pleuro-fibrinolysis)].
AB  - The main causes of pleural fluid drainage failure are known to be the formation
      of fibrin septa, increased viscosity in pleural fluid and inappropriate placement
      of chest tubes. Reports also tell us that such problems can be solved by using
      ultrasound as a guide for tube placement and by infusing intrapleural
      fibrinolytic agents to prevent the formation of septa and reduce the viscosity of
      pleural fluid. To assess our experience, the role and efficacy of administering
      intercavitary urokinase (UK) through a small caliber catheter (SCC) implanted
      with ultrasound guidance as part of the treatment for pleural effusions (PE) that
      are multiloculated and/or loculated. Fifty multiloculated and/or loculated PE
      were drained through a pig-tail type SCC between 8.2 and 10 F caliber inserted
      with ultrasound guidance. The criteria for prescribing the procedure were as
      follows: PE of any etiology with ultrasound confirmation of fibrin septa and/or
      multiloculation and absence of contraindication off UK administration. UK was
      given at a dose of 100,000 i.u. every two hours until disappearance of PE. Before
      and after treatment the levels of D-dimer were measured in order to monitor
      pleural fibrinolytic activity. The SCC was properly placed in all patients. UK
      administration was 366,000 i.u. and time the SCC were in place was 4.7 days. All
      PEs were initially drained completely. We examined the patients 30 days later,
      finding that PE had recurred in 2 (4%), resolution was complete and without
      sequelae in 8 (16%), nearly complete but with slight pleural thickening in 32
      (64%) and partial with pleural opacities larger than 2 mm in 8 (16%). Use of SCC
      and UK (pleural fibrinolysis) is a moderately invasive procedure that is
      effective and well tolerated and that shortens drainage time, prevents sequelae
      and is relatively inexpensive for the treatment of PE with fibrin septation
      and/or multiloculation.

PMID- 9019311
TI  - [Compliance with the "recommendations SEPAR" on spirometry].
AB  - The objective of this study was to assess Spanish performance of spirometry and
      to determine the extent to which practice is in accordance with the 1985 SEPAR
      recommendations. To that end we formulated a questionnaire with 31 items in two
      sections, 10 covering basic aspects of compliance with necessary techniques and
      21 general questions. The questionnaire was sent to all SEPAR members. One
      hundred eight responses were received. The results show that the typical
      spirometric measurement was forced expiration without a bronchodilator test by
      way of a pneumotacograph, with simultaneous representation of the flow/volume
      curve. Calibration, when performed, is done daily with a 3 1 syringe and
      atmospheric data are checked. Spirometric measurements are usually obtained by a
      registered nurse, who also collects anthropometric data directly from the
      patient. The patient is usually seated with the nose occluded. At least three and
      at most eight satisfactory readings are obtained. The criteria for starting and
      ending the maneuver and the reference values used are those recommended by SEPAR.
      The equipment is washed weekly with soap and water; calibrations and equipment
      incidences are not recorded. The level of compliance with 1985 SEPAR norms for
      forced spirometry is adequate with respect to some technical equipment questions
      but deficient on basic procedure and quality control.

PMID- 9019312
TI  - [Comparative study of soluble interleukin 2 receptor and adenosine deaminase
      levels in tuberculous and other etiologies pleural fluids].
AB  - In order to better understand the immunological mechanisms involved in host
      protection against Mycobacterium tuberculosis infection, we studied soluble
      interleukin 2 receptor (sIL-2R) concentration in tuberculous pleural exudates as
      well as in pleural fluids of non-mycobacterial etiology. We collected pleural
      fluid from 40 patients: 10 with tuberculous bacterial pneumonia and 10 with
      trasudate. Soluble IL-2R was measured in the stored specimens using a standard
      ELISA technique. In patients with tuberculosis, sIL-2R in pleural fluid was
      14,666 +/- 5,634 U/ml, significantly higher than was detected in any other group,
      being 4,341 +/- 2,655 U/ml in pneumonic exudates, 5,542 +/- 3,682 U/ml in
      neoplastic exudates and 1,377 +/- 125 in trasudates (p < 0.001). Also, an
      excellent correlation was demonstrated between adenosine-desaminase (ADA) and sIL
      2R in tuberculous pleural fluids, with p < 0.001 and r = 0.805. In
      pleuropulmonary tuberculosis, compartmentalization of the immune response in the
      pleural space is responsible for the significantly higher levels of sIL-2R that
      were found in tuberculous pleural liquids compared with the ones detected in
      other diseases. This observation, as well as the demonstration of a good
      correlation between sIL-2R and ADA, suggest the possible usefulness of this
      molecule as an additional marker in the differential diagnosis of pleural
      effusions, though in the present study it appears to be less reliable than ADA.

PMID- 9019313
TI  - [Mechanisms of action of glucocorticoids. Application to the treatment of
      respiratory inflammation].

PMID- 9019314
TI  - [Books published in Spain on smoking].
AB  - Tobacco dependence, considered for a long time as a habit and, more recently, as
      an addiction, has many bad effects in health. The objective of this study was to
      analyse books published in this field in Spain. Books indexed in the ISBN Spanish
      database in CD-ROM (updated to 1993) dealing with addiction to tobacco, that
      included one of the following words: tabac*, tabak*, tabaq*, fuma*, fumad*,
      nicotine*, alquitran*, antitabac*, antitabaq*, cigarro*, cigarri*, exfumad*,
      pipa*, puro*, picadura* or filtro, were included in the study. Authors, ISBN
      classification, year of publication, language (of publication and original) and
      publishers were descriptively analysed. One hundred and four books were analysed.
      The highest number was published during the period 1990-1993 (42%); being 1993 (n
      = 15) and 1991 (n = 14) the most productive years. A big increase was observed
      from 1985. A great number (76% of books, n = 79) was written by personal authors
      and the 14% (n = 14) by public organizations. Most of the books (n = 88; 85%);
      were published in Spanish, followed by Catalan (n = 13; 13%); 21 books (20%) were
      translations: most of them from English (n = 12; 60%) or from French (n = 3;
      14%). Forty six per cent of books was published by trade publishers and 31% by
      public organizations. According to the ISBN classification, these books were
      grouped in 20 different topics; but, most of them (70%) were included in three of
      these topics: hygiene (n = 42, 40%), pharmacology-toxicology-drugs (n = 18, 17%)
      and pathology-diseases and medical/therapeutical clinical practice (n = 14; 13%).
      The number of books published in Spain dealing with tobacco dependence has
      increased very much from 1985; it suggests that interest in this area in SPain
      has also increased. Most of the books are published in Spanish, and the most
      frequently translated language is English. These books are basically published by
      trade publishers and public organizations. These results have to be considered
      taking into account that fighting against consumption of tobacco and tobacco
      dependence is a relatively new area of research and study.

PMID- 9019315
TI  - [Surgical treatment of sternoclavicular osteomyelitis].
AB  - Osteomyelitis of the sternocosto-clavicular (SCC) articulation is a rare
      infection usually caused by Staphylococcus aureus and enterobacteria. It usually
      occurs in individuals with osteoarticular disease or predisposing factors.
      Prolonged antibiotic treatment and articular puncture are generally accepted.
      Authors do not agree on an established protocol. We report three cases of SCC
      septic arthritis in two previously healthy patients with two foci of infection
      (one perianal abscess and one dental extraction) and in one adult patient with
      Still's disease. Pain and intense inflammation was referred to the shoulder, with
      scarce leukocytosis and fever reaching 38 degrees C. The germs responsible were
      S. aureus, Bacteroides fragilis and B. oralis. Two of the patients had local,
      regional abscesses. Long-term antibiotic treatment failed in all cases and
      surgery for SCC resection and myoplasty of the pectoralis major muscle was
      required. Recovery was good and shoulder and arm mobility was excellent. We
      propose medical treatment and articular diagnostic-therapeutic puncture as the
      first line of therapy for this disease. When evolution is poor or when
      complications appear, such as abscesses or mediastinitis, we conclude that
      radical debridement and myoplasty of the pectoralis major muscle are indicated.

PMID- 9019316
TI  - [Bilateral pneumonia after localized irradiation of a thymoma. Description of a
      case].
AB  - Acute pneumonitis characterized by fever, coughing and moderate dyspnea can
      appear from 6 to 12 weeks after irradiation. Most patients later show signs of
      fibrosis confined to the irradiated field. An entity that has been under recent
      discussion is "radiation-induced sporadic pneumonitis", a bilateral lymphocytic
      alveolitis of autoimmune origin that leads to generalized pulmonary response
      after local irradiation. The prognosis for such cases is good. We report a case
      of early post-irradiation pneumonitis of the type described, which led
      unexpectedly to the patient's death.

PMID- 9019317
TI  - [Obstructive apnea syndrome during sleep secondary to a pharyngeal lymphoma.
      Improvement with continuous pressure treatment of the upper airway].
AB  - Obstructive sleep apnea syndrome (OSAS) is characterized by multiple episodes of
      upper airway (UA) obstruction during sleep. Patients experience daytime
      hypersomnia, sluggishness and inability to concentrate; snoring at night is
      common. We report the case of a man with Hodgkin's lymphoma without full
      remission and with pharyngeal recidivism leading to OSAS. He experienced marked
      diurnal hypersomnia accompanied by behavior disorders. Examination revealed flow
      volume OSAS, suggesting UA instability. Cervical computed tomography showed a
      prevertebral lymphomatous mass in the pharynx causing significant UA compression.
      UA size increased considerably after use of continuous positive airway pressure
      (CPAP), which normalized sleep and produced significant relief of symptoms.
      Later, after chemotherapy, OSAS resolved and the patient was able to abandon CPAP
      treatment.

PMID- 9019318
TI  - [Usefulness of the rapid diagnosis of Haemophilus influenzae in respiratory
      samples].

PMID- 9019319
TI  - [What is the real international dissemination of Archivos de Bronconeumologia?].

PMID- 9019320
TI  - [Sclerosing hemangioma of the lung: apropos of a case of rapid growth].

PMID- 9019321
TI  - [Fulminant hepatic insufficiency secondary to a metastatic pulmonary
      adenocarcinoma].

PMID- 9019322
TI  - The role of MRI in the assessment of rheumatological disease. Proceedings of an
      international symposium. Otocec, Slovenia, November 1995.

PMID- 9019323
TI  - [Academician F.G. Krotkov in the development of scientific hygiene in Russia and
      abroad].

PMID- 9019324
TI  - [Radon and its decay products in the air of preschool institutions of Serpukhov].
AB  - The article deals with some methodic recommendations associated with examination
      of "radon" factor in preschool institution buildings. The recommendations result
      from analysis of general and selected studies that covered preschool institution
      buildings varying in length of service in Serpoukhov town of Moscow region in
      1993-1994. The examinations were carried out by Serpoukhov State Center for
      Sanitary and Epidemiologic Supervision in accordance with Regulation Document No
      5789-91. In order to reveal the buildings with higher possible occurrence of
      maximal allowable concentrations of radon and its derivatives, as the studies
      proved, the examinations in the region are expedient in the summer morning hours.

PMID- 9019325
TI  - [Ecological aspects of electromagnetic radiation emitted by mobile stations of
      communication means].
AB  - Electromagnetic environment of staffers using mobile communication means is
      characterized by complicated field structure with prevalent magnetic load.
      Biologic effects of the field parameters depend to large extent on location of
      emitting source and exposed object, presence of reflecting articles and grounding
      in the neighborhood. Human body is sensitive to electromagnetic influence on the
      certain organs.

PMID- 9019326
TI  - [Hygienic regulation of electromagnetic radiation of 300-3000 MHz frequency
      range].
AB  - The article contains analysis of national standards determining maximal allowable
      levels of electromagnetic exposure in some developed countries. The point of
      specific interest is the levels in frequency range of 300 MHz-30 GHz, as this
      range is widely used in most apparatus for mobile communication. Different in
      various countries, values of the maximal allowable levels appear to be the most
      strict in Russia. Incomplete knowledge of long-standing exposure to mild
      electromagnetic fields requires through medical and technical research to
      determine limits of safe application of mobile communication devices.

PMID- 9019327
TI  - [Mortality of people residing near electric power supply line with voltage of 500
      kV].
AB  - The epidemiologic study covered causes and levels of mortality in the settlement
      situated near electric power supply line (voltage is 500 kV). The work used
      retrospective cohort method adjusted for evaluation of mortality in general
      population. The study revealed no higher mortality risk with all the causes
      totally and with leading causal groups under influence of high frequency
      electromagnetic fields. However, higher relative mortality risk with leukemia and
      suicide appeared statistically insignificant.

PMID- 9019328
TI  - [Features of control of electromagnetic radiation emitted by personal computers].
AB  - Measurements of PC electromagnetic irradiation show that the main sources are PC
      blocks emitting the waves of certain frequencies. Use of wide-range detectors
      measuring field intensity in assessment of PC electromagnetic irradiation gives
      unreliable results. More precise measurements by selective devices are required.
      Thus, it is expedient to introduce a term "spectral density of field intensity"
      and its maximal allowable level. In this case a frequency spectrum of PC
      electromagnetic irradiation is divided into 4 ranges, one of which is subjected
      to calculation of field intensity for each harmonic frequency, and others undergo
      assessment of spectral density of field intensity.

PMID- 9019329
TI  - [Direct effects of low-frequency acoustic oscillations on cell membranes].
AB  - Acoustic waves of low frequency appeared to influence directly the body cellular
      structures, induce non-specific changes of cells and subcellular elements in all
      organs and systems studied. Direct correlation exists between the waves
      frequency, exposure period and severity of the disorders. The most severe
      disorders result from the frequencies of 8 and 16 Hz. Evaluation of RBC membranes
      permeability through a method of urea-induced hemolysis is non-specific but quite
      sensitive test that could be recommended for screening among individuals exposed
      to occupational factors.

PMID- 9019330
TI  - [Carcinogenic effects of radon in humans (literature review)].

PMID- 9019331
TI  - [New approaches to hygienic regulation of visible radiation].
AB  - There are no medical documents on control over light factors of industrial and
      living compartments. Levels of illumination in the present construction norms
      (SNiP-23-05-95) are not justified physiologically. Data of long-standing
      observations of objects brightness made an essence of project called "Brightness
      (illumination and light) of workplaces in industrial enterprises, institutions
      and living compartments" and demonstrated in the article.

PMID- 9019332
TI  - [Medical aspects of the use of gas jets with infrared irradiation for heating of
      industrial accommodations].
AB  - Up-to-date research, results of experimental and pilot studies of gas radiative
      heating helped to justify hygienic, sanitary and technical requirements
      concerning air quality in heated compartments, to determine values of infrared
      irradiation on various body sites, that are not hazardous for human functional
      state. Radiation doses received by the workers are set in accordance with ambient
      temperature decrease compared to the normal values in convective heating systems.
      The authors adjusted parameters of microclimate in compartments heated by gas
      radiative systems and some methods evaluating the ambient air.

PMID- 9019333
TI  - [Experimental studies of electromagnetic radiation emitted by personal computer
      displays].

PMID- 9019334
TI  - [Legal guarantees of radiation safety for Russian population].

PMID- 9019335
TI  - [Ways to reduce radiation doses caused by radon during exploration of gas and oil
      fields in the North].
AB  - Analysis of literature data and the personal studies of oil and gas extraction
      enterprises proved that the radiation environment depends mainly on natural
      radionuclides (uranium-238, thorium-232, potassium-40) incorporated into soil,
      deposit water, oil, gas and construction materials. Radioactive barytic
      accumulations in compressor pump tubes appeared to b a possible cause for
      significant background gamma-irradiation (up to 3,000 microR/hr and more;
      Neftekoumsk town of Stavropol area). Major radiation dose received by personnel
      in such cases results mainly from radon-222 and its derivatives, that should be
      considered in placement of living area, location of industrial and special
      compartments, water extraction sites. The places with minimal rate of radon
      emission are recommended for such purposes. To decrease radiation doses
      associated with gas and oil extraction in the North, the authors suggested a
      scheme of radiation control and listed all the equipment necessary.

PMID- 9019336
TI  - Child care resource and referral agencies.

PMID- 9019337
TI  - Financing early childhood facilities.

PMID- 9019338
TI  - Statewide initiatives for financing early childhood care and education.

PMID- 9019339
TI  - Polarized views.

PMID- 9019340
TI  - [ACE-inhibitors in the treatment of chronic heart failure: pathophysiologic
      principles of protective effects].
AB  - The aim of modern therapy of heart failure is not a pure removal of symptoms but
      an improvement of survival. The angiotensin-converting enzyme (ACE)-inhibitors
      reduced morbidity and mortality in several large clinical trials in patients with
      dysfunctional left ventricle or manifestant heart failure. Thus, ACE inhibitors
      are recommended for heart failure treatment as a drug of primary option, unless
      contraindications are present, and if tolerated by patient. The mechanism of
      action of ACE inhibitors in heart failure is hypothetical. Participation of three
      factors is supposed: improvement in the pumping function of the failing heart,
      reduction on the risk of sudden death and reduction in myocardial infarction
      incidence. Reduction of hemodynamic load, antiischemic action and reduction of
      fibrotic tissue proliferation in failing myocardium are responsible for heart
      function improvement. These mechanisms together with potential
      antiatherosclerotic, antiaggregative, fibrinolytic and protective effect on
      endothelial function are supposed to participate in reduction of acute myocardial
      infarction and sudden death origin. The mentioned effects are determined by
      interaction with both circulating and local renin-angiotensin systems. The
      negative hemodynamic effects and undesirable restructuralisation of the affected
      ventricle are thus influenced on systematic and local-tissue level. Similarly as
      any other therapy also the treatment of heart failure with ACE inhibitors needs
      experience and a rational well tailored individual approach. (Fig.1, Ref. 32.).

PMID- 9019341
TI  - [Disorders of hepatic circulation and imaging with color doppler
      ultrasonography].
AB  - The authors analyse disturbances of hepatic circulation and the possibilities of
      their imaging by colour Doppler ultrasonography (CDU) in combination with
      standard B two-dimensional imaging. The predominance of arterial perfusion in
      liver cirrhosis, portal vein thrombosis, malign diseases of the liver, or
      extraluminal obstruction of portal vein are changes which can be imaged by means
      of high-quality colour Doppler imaging. CDU is a non-invasive method of
      evaluation of portal hypertension, namely of prehepatic, hepatic and posthepatic
      type. It is a method of investigation of the viability of the hepatic artery
      after transplantation of the liver, including that of surgical portocaval
      anastomoses and transjugular intrahepatic portosystemic shunts. (Fig. 6, Ref.
      33.).

PMID- 9019342
TI  - [Coenzyme Q10 and alpha-tocopherol in patients after heart transplantation].
AB  - Pathobiochemical mechanisms which participate in the rejection of transplanted
      heart are not fully clarified. A significant role in this process can be played
      by endogenous antioxidants, especially coenzyme Q10 which aside from its
      antioxidative properties is inevitable for cellular bioenergy. The authors
      investigated the concentration of Q10 alpha-tocopherol in endomyocardial biopsies
      in the blood in 11 patients from 1 to 9 years of age after transplantation of the
      heart (HTx-pat) examined in UKVCH in Bratislava who were compared with the group
      of 13 patients with cardiopathies of unclear origin (KPNP-pat) as possible
      candidates for transplantation. They detected a decreased concentration of
      coenzyme Q10 in the myocardium and blood of HTx-patients. Levels of alpha-to
      copherol in the myocardium were identical in both groups, in plasma they were
      higher in patients after HTx. The authors suppose that the levels of coenzyme Q10
      in patients after HTx can be influenced by an increased production of free oxygen
      radicals during rejection episodes, as well as immunosuppressive therapy, and
      indicate to the possible consequences of this decrease. The presented results
      provide the first information on the levels of coenzyme Q14 and alpha-tocopherol
      in patients after transplantation of the heart, registered and controlled in the
      Slovak Republic. They can contribute to the clarification of some
      pathobiochemical mechanisms of rejection, respectively to their therapeutic
      effect. (Fig. 2, Ref. 16.).

PMID- 9019343
TI  - [Identification of inhaled dust with a noninvasive magnetometry method].
AB  - The authors performed an examination of the degree of lung contamination by
      magnetic compounds present in gases originating during welding in 33 persons
      divided into four groups. The measurement was performed by a noninvasive
      magnetometric method using a high sensitive SQUID and second degree gradiometric
      antenna with presumed maximum sensitivity of 60 micrograms of magnetic
      compound/cm3. In the selected three groups of welders working for a long period
      of time under the conditions of exposure, the changes of the magnetic field were
      particularly evident in the group working in small confined spaces. It has become
      obvious that further improvement in the accuracy of the detected results in the
      lung may be reached in the subjects by changing the polarity of magnetization.
      (Fig. 4, Ref. 13.).

PMID- 9019344
TI  - [Mitochondrial bioenergetics in patients before and after heart transplantation].
AB  - BACKGROUND: The results of the study of biochemical and genetic characteristics
      of mitochondria in human medicine become widely used in practice. This is
      confirmed also by the Nobel Symposium which took place in 1994, and was dedicated
      to the problem of mitochondrial diseases and the effect of their therapy.
      Relatively rare is the information on the pathobiochemistry of heart muscle
      mitochondria in patients with cardiomyopathies. No information, so far, is
      available on oxidative phosphorylation in cases of myocardium transplantation in
      patients. MAIN PURPOSE AND OBJECTIVES: To bring early metabolic changes in
      mitochondria within EMB (endomyocardial biopsy) under control in patients after
      transplantation of the heart (Htx). These detected metabolic changes can
      contribute to the clarification of the mechanisms participating in the rejection
      of the transplanted myocardium. PATIENTS AND METHODS: The investigated group of
      patients included: a) patients with cardiopathies of unclear origin (NYHA II,
      NYHAIII) b) patients after transplantation of the heart (NYHAI-II) The authors
      assessed the properties of the respiratory chain and ATP production in
      mitochondria of EMB. CONCLUSIONS: The new methodical approach to the study of
      bioenergy of mitochondria of the myocardium in patients allows an early
      recognition of pathobiochemical changes in myocardium. Supplementing studies are
      going to reveal wether the presented methodical approach bear diagnostic value.
      (Fig. 3, Ref. 25.).

PMID- 9019345
TI  - [Bioenergetics of liver mitochondria in rats in experimental insulin-dependent
      diabetes].
AB  - Oxidative stress in the course of diabetes mellitus can cause disturbance of
      lipid membranes of cellular organelles. The study is aimed at the determination
      of oxidative phosphorylation in mitochondria in rats with experimentally induced
      acute and chronic insulin-dependent diabetes mellitus (IDDM). IDDM was induced by
      single dose of streptozotocin (45 mg per kg-1). Insulin Interdep (6 U per kg-1)
      was administered once a day subcutaneously. The authors investigated glycaemia,
      cholesterol and triacylglycerol concentrations in the blood and liver. Isolation
      of mitochondria was succeeded by measurement of oxidative phosphorylation
      indicators after 8 days (acute IDDM) or after 8 weeks (chronic IDDM) from
      streptozotocin administration. The authors found out that both acute and chronic
      IDDM were concommited by hyperglycaemia. The group with acute IDDM yielded an
      increase in cholesterol and triacyglycerols concentrations in the blood, as well
      as that of cholesterol in the liver. The group with chronic IDDM yields an
      increase in cholesterol in the blood. Trialcylglycerols in the liver increased in
      none of the investigated groups. Liver steatosis did not occur. Indicators of
      oxidative phosphorylation in the liver mitochondria of rats with acute and with
      chronic IDDM decreased in contrast to healthy controls from NAD substrates
      glutamate and pyruvate and also form FAD substrate of succinate. Significant
      decrease in consumption of oxygen in the 3 state occurred, while in acute IDDM
      the decrease was more significant than in chronic IDDM. Phosphorylation rate
      significantly decreased in contrast to controls, but there was no difference
      between IDDM groups. The investigation results imply that in both acute and
      chronic IDDM there are decreased effectivity of energetic metabolism in liver
      mitochondria. (Tab. 5, Ref. 29.).

PMID- 9019346
TI  - [Plasma proteins in patients with liver steatosis and the effect of treatment of
      essential phospholipids].
AB  - BACKGROUND: Steatosis of the liver is the most frequent diffuse disturbance of
      liver parenchyma. Accumulation of fat droplets in hepatocytes determine the
      damage of function of subcellular structures and energy metabolism of liver
      cells. The damagables include functions also the synthesis of phospholipids which
      are required for the correct function of membranes. Essentiale forte is a mixture
      of choline phosphatides with high content of polyenic carboxylic acids. In our
      study we were interested in the effect of administration of the drug Essentiale
      forte to patients with liver steatosis. PATIENTS: An open clinical trial was
      performed in 29 patients (15 men and 14 women) suffering from liver steatosis.
      Two capsules of Essentiale forte (Rhone-Poulenc Rorer) were administered 3 times
      daily for 3 months. Individual biochemical parameters were determined each month.
      RESULTS: The therapeutic effect of the substance on the patient's well-being and
      the clinical condition was assessed as being good in 23 patients (76%). There was
      a significant improvement in parameters of hepatocyte integrity
      (aminotransferases) and a decrease of activity of gamma-glutamyltransferase in
      sera of patients after therapy. In the group of acute phase proteins there was a
      significant decrease in the alpha-1-acid glycoprotein level. A similar tendency
      was also in the level of haptoglobin. In the group of the parameters of
      proteosynthetic function of the liver (albumin, transferrin, prealbumin) there
      was no change. Statistically significant decreases were detected also in the
      levels of immunoglobulins G and M. CONCLUSION: The submitted findings confirm
      positive effect of essential phospholipids on the treatment of liver steatosis.
      (Fig. 4, Ref. 15.).

PMID- 9019347
TI  - [The role of vascular reconstructive surgery in the treatment of cerebrovascular
      insufficiency].
AB  - BACKGROUND: Management of cerebrovascular insufficiency (CVI) is one of the
      greatest medical challenges in our country. Retardation in this field has been
      causing serious medical and socioeconomic consequences. MAIN PURPOSE AND STARTING
      POINTS (OBJECTIVES): In spite of existing unfavourable conditions the authors of
      this paper have managed to standardize their own policy in diagnosis, surgical
      indications and techniques. This caused substantial improvement of their results,
      as well as cooperation with the neurologic clinics. In connection with the
      increasing numbers of operations and improved results, the authors report their
      recent experience in this field and compare them with the results from previous
      years. METHODS: The authors compare two series of patients. The first series of
      65 consecutive patients surgically treated from 1st Jan. 1987 to 31st Dec. 1990
      (69 operations altogether). The 2nd series of 169 consecutive patients surgically
      treated from January 1st 1993 to December 31st 1994 (191 operations altogether),
      149 due of them were subjected to carotid endarterectomy (CEA). Mean age of the
      first series was 55.3 (35-73), 2nd series 59.7 years (42-86). The authors have
      studied participation of neurologically and angiographically unstable patients.
      In the first series the ratio of neurologically stable and unstable patients was
      63.4:36.6%, while in the 2nd series it was 75.4:24.6%. The ratio of
      angiographically stable and unstable patients was in the 1st series 60.2:39.8%,
      while in the 2nd series it was 50.3:49.7%. In the 2nd series the authors observed
      also the percent age of ulcerated lesions in the carotid bifurcation and found a
      surprisingly high number-59.2%. RESULTS: The combined mortality-morbidity index
      of the first series was 11.6%, of the 2nd series 3.1%. In the first series there
      were two deaths (2.9%) and 6 brain infarctions. In the 2nd series four patients
      died from acute myocardial infarction (2.1%) and there were two cases of a
      perioperative brain infarction, respectively. The necessity of wound revision due
      to of bleeding was found in two patients (2.9%) in the first series, and in two
      cases (1%) in the 2nd series. CONCLUSIONS: The authors emphasize the complicated
      nature of these problems, the necessity to recognize the surgical indications and
      techniques, and protective measures to prevent serious complications. There is,
      in their opinion, inevitable to increase bringing the patients in need of
      surgical reconstruction under control. On the other hand, there is the necessity
      to increase the accessibility of qualified surgery in the CVI. That means in the
      first place to increase the number of centers able to accomplish these operations
      with minimal combined mortality-morbidity index. (Tab. 10, Ref. 37.).

PMID- 9019348
TI  - Molecular determinants in the biology of liver metastasis.
AB  - A primary goal of cancer research is an increased understanding of the molecular
      mechanisms mediating the process of cancer metastasis. Analyses of colon cancer
      cells (the seeds) and the microenvironment (the soil) has increased our
      understanding of the biologic mechanisms mediating liver-specific metastasis.
      Insight into the molecular mechanisms regulating the pathobiology of cancer
      metastasis as well as a better understanding of the interaction between the
      metastatic cell and the host environment should produce a foundation for new
      therapeutic approaches. In this article we summarize experimental observations
      demonstrating the importance of specific factors that regulate various steps in
      the metastatic cascade. Furthermore, this article emphasizes the importance of
      the host organ's microenvironment and its role in liver metastasis formation. The
      production of metastases depends, in part, on the interaction of particular tumor
      cells with specific organ environments. Therefore, the successful metastatic cell
      must be viewed currently as a cell receptive to its environment. The analyses
      presented herein add important evidence to support the concept that cancer
      metastasis is not a random process; it is a highly regulated process that can be
      analyzed on the molecular level. To the clinician, it is readily apparent that by
      the time metastasis forms, most steps in the metastatic cascade have been
      completed. Therefore, therapy targeted to downregulate or interrupt the last
      stages of metastasis, proliferation and angiogenesis, should be the areas of
      greatest investigation in regards to treating established metastasis, whether
      they are microscopic or macroscopic.

PMID- 9019349
TI  - Imaging of primary and metastatic liver tumors.
AB  - Innovative liver surgical techniques are allowing improved survival for patients
      with liver tumors. To effectively plan this surgery, both the number and precise
      location of all lesions must be accurately documented. Numerous technical
      advances have occurred in cross-sectional imaging techniques for evaluating liver
      tumors. These improvements have increased the sensitivity of US, CT and MR for
      detecting primary and metastatic liver neoplasms. Depending on the specific
      clinical information required, such as extrahepatic spread of diseases or hepatic
      vascular invasion, each modality has its strengths and drawbacks. The specific
      choice of technique should be decided in consultation with the radiologist who
      interprets the studies. Both benign and malignant lesions may coexist in the same
      liver and, because this affects patient management and prognosis, care should be
      taken to evaluate each lesion that is identified. Tumors also may be simulated by
      pseudolesions such as focal fatty sparing or infiltration, regenerative nodules,
      or hepatic arterial perfusion defects. To best evaluate liver malignancies, a
      sensible combination of imaging modalities, depending on the patient population,
      radiologic strengths, and imaging equipment available, is recommended to provide
      the best overall assessment of the number and location of liver neoplasms.

PMID- 9019350
TI  - Intraoperative ultrasonography and other techniques for segmental resections.
AB  - Intraoperative ultrasonography is an indispensable tool for liver surgery, and
      ultrasonically guided techniques have opened the way to new hepatectomy
      procedures, namely, segmental and subsegmental resections, thereby allowing minor
      but systematic resection in patients with poor hepatic function.

PMID- 9019351
TI  - Laparoscopic staging and intraoperative ultrasonography for liver tumor
      management.
AB  - Intraoperative ultrasonography has become an invaluable tool for programs that
      perform large volume, complex liver operations. Together with laparoscopy,
      intraoperative ultrasonography helps in appropriate staging, aids in decision
      making, and tailors operations so as to minimize short-term morbidity and
      optimize long-term benefit.

PMID- 9019352
TI  - Primary epithelial hepatic malignancies: etiology, epidemiology, and outcome
      after subtotal and total hepatic resection.
AB  - Primary hepatic malignancies are among the leading causes of cancer deaths. The
      epidemiology, natural history, and staging of primary hepatic tumors are
      reviewed. Both subtotal hepatectomy and total hepatectomy with liver
      transplantation are appropriate therapeutic options based on careful patient
      selection. Prognostic factors related to these tumors also are reviewed.

PMID- 9019353
TI  - Cholangiocarcinoma.
AB  - Resection is indisputably associated with prolongation of survival in patients
      with cholangiocarcinoma and provides the only chance for cure. Equally as
      important is the ability to achieve microscopically clean margins at the time of
      resection. Liberal use of hepatic resection in conjunction with hilar vascular
      skeletonization may improve the ability to achieve disease-free margins and can
      be performed with little additional morbidity. Optimal treatment for the patient
      with unresectable disease is currently still debatable. Our experience, as well
      as others, suggests that patients who have unresectable disease by radiologic or
      laparoscopic evaluation are better served by nonsurgical internal biliary
      decompression. We currently favor nonoperative treatment with self-expandable
      wire mesh stents over operative biliary enteric bypass for nonresectional
      candidates. Patients who underwent resection who develop local recurrence with
      biliary obstruction also can be managed with metallic stents across the
      obstructed hepaticojejunostony to provide an additional period of symptomatic
      palliation.

PMID- 9019354
TI  - Proximal bile duct tumors.
AB  - Modern radiologic diagnostic approaches that identify patients with high bile
      duct cancer can predict resectability and provide information for biliary-enteric
      bypass in the case of irresectability. Twenty percent to 40% of patients are
      resectable by local excision with or without hepatic resection, and this
      represents the only opportunity for cure. Operative mortality is now acceptable
      and resection is associated with a median survival of approximately 35 months.
      Numerous palliative operative and nonoperative approaches are available,
      including biliary-enteric bypass, transtumoral stenting, and percutaneous
      endoprostheses. The role of both intraluminal and external beam radiotherapy also
      is discussed.

PMID- 9019355
TI  - Surgical resection of metastatic liver tumors.
AB  - The liver is a common site of metastatic cancers. Abundant data now support
      surgical resection as the treatment of choice for metastatic colorectal cancer to
      the liver. For symptomatic neuroendocrine tumors, resection also is a useful
      palliative therapy. Roles for resection of metastatic cancer from other primary
      sites have yet to be defined.

PMID- 9019356
TI  - Re-resection for colorectal liver metastasis.
AB  - With the decreasing mortality and morbidity of liver resection in the last 10
      years, a more aggressive approach has emerged against liver metastases of
      colorectal cancer. Repeat liver resection is being performed for patients with
      isolated liver recurrence following a first hepatectomy. Based on a 2-year
      experience of 55 repeat hepatic resections performed in 44 patients, the authors
      observed no operative mortality and a postoperative morbidity of 15% similar to
      that of first hepatectomies. Five-year survival rate is 44% following second
      hepatectomy. These results combined with the review of the literature demonstrate
      that rehapectomy may be performed safely and may provide the only chance of long
      term remission in patients presenting with technically resectable liver
      recurrence in the absence of widespread extrahepatic disease.

PMID- 9019357
TI  - Interstitial therapies for liver tumors.
AB  - A variety of tumor-directed "interstitial" treatments based on physical,
      chemical, and radiobiologic antineoplastic principles have been investigated for
      the management of patients with unresectable tumors confined to the liver.
      Cryosurgery, ethanol injection, and laser photocoagulation are reviewed.

PMID- 9019358
TI  - Ablative approach for primary liver cancer: Shanghai experience.
AB  - This article summarizes the results of 2018 patients receiving surgical treatment
      for pathologically proven primary liver cancer (PLC). Special references are made
      to the role of cryosurgery and cytoreduction for unresectable PLC.

PMID- 9019359
TI  - Australian experience of cryoablation of liver tumors: metastases.
AB  - The authors' clinical experience of treating almost exclusively inoperable liver
      malignancy in 149 patients by cryotherapy is reviewed. There was only one 30-day
      death; morbidity was modest. Postoperative carcinoembryonic antigen (CEA) changes
      were extremely predictive of outcome in patients with liver metastases from
      colorectal cancer. For the group in which CEA levels returned to the normal
      range, median survival exceeded 1000 days. In addition, the authors reported
      encouraging results with cryotherapy as an adjunct to resection.

PMID- 9019360
TI  - Theoretic and experimental aspects of regional liver infusion.
AB  - Pharmacokinetic theory of hepatic arterial infusion chemotherapy predicts that
      parameters, such as hepatic blood flow, hepatic drug extraction, and extrahepatic
      drug clearance, may potentially be manipulated to enhance the selectivity of
      hepatic artery drug administration. In practice, diminution of hepatic blood flow
      through the use of degradable starch microspheres or gelatin sponge embolization
      has been accomplished and has improved drug selectivity. Likewise, augmentation
      of hepatic drug extraction improves the pharmacokinetic advantages of regional
      chemotherapy for liver tumors. Development of optimal hepatic infusion
      chemotherapy approaches can be undertaken rationally and in an expeditious
      fashion by applying pharmacokinetic principles to create innovative treatment
      regimens and by testing them in preclinical and phase I investigations.

PMID- 9019361
TI  - Regional chemotherapy approaches for primary and metastatic liver tumors.
AB  - There are pharmacologic principles that make regional chemotherapy to the liver a
      logical treatment strategy. Patients with colorectal liver metastases and
      hepatocellular carcinoma would appear to be the best candidates for such an
      approach. Although there are many objective responses to such treatment, survival
      benefit has not been demonstrated, but new regimens and refined techniques appear
      to be improving results. Ultimately, regional delivery may be best suited for
      innovative treatments such as biologicals and gene therapies.

PMID- 9019362
TI  - Clinical and preclinical trials of isolated liver perfusion for advanced liver
      tumors: primary liver tumors.
AB  - Preclinical serum and tissue pharmacology studies have played a key role in the
      development and testing of this novel system designed to treat liver tumors.
      Pharmacologic evaluation confirmed that the CVHI-CF system significantly limited
      systemic serum and tissue exposure to chemotherapy drugs given by HAI. By
      reducing systemic drug exposure and, thus, limiting systemic toxicity, higher
      doses of antitumor agents can be administered to enhance intratumoral drug levels
      and increase tumor cell kill. The CVHI-CF system will likely prove increasingly
      valuable as more active chemotherapeutic agents are developed to treat hepatic
      malignancies.

PMID- 9019363
TI  - Isolated liver perfusion for liver metastases: pharmacokinetic advantage?
AB  - The pharmacokinetic advantage of a novel system to noninvasively isolate the
      hepatic venous outflow and infuse high doses of chemotherapy (doxorubicin or 5
      FU) is discussed and compared with intravenous infusion and intra-arterial
      infusion without hepatic venous detoxification. This dose intensification schema
      may provide new pharmacokinetic and pharmacodynamic principles for the treatment
      of a variety of tumors metastasizing the liver, including melanoma, sarcoma, and
      adenocarcinoma.

PMID- 9019364
TI  - Management of pediatric liver tumors.
AB  - Historically, children with liver tumors were uniformly considered to have a poor
      prognosis and were approached warily by pediatric surgeons and oncologists. Over
      the last decade, however, advances in diagnostic imaging technology, discovery of
      effective chemotherapy, and improved surgical techniques have greatly facilitated
      the management of children with hepatic tumors. Although orthotopic liver
      transplantation has emerged as a viable treatment option in the management of
      hepatic malignancies, including hepatoblastoma and hepatocellular carcinoma, its
      use is still controversial.

PMID- 9019365
TI  - Gene therapy for liver tumors.
AB  - Therapeutic gene transfer has progressed quite rapidly in recent years.
      Noticeably, it has now reached the clinical stage in both fields of inherited and
      acquired diseases. Numerous studies of liver-targeted gene therapy and cancer
      gene therapy have supported the hope that such innovative approaches may be of
      help in the treatment of primary or secondary liver tumors. In this article, the
      main strategies of experimental, hepatic cancer gene therapy in the prospect of a
      clinical use are reviewed.

PMID- 9019366
TI  - Overview and future prospects.
AB  - At present, resection affords highly selected patients with limited liver cancer
      their only choice for cure. Palliation with currently available agents and
      techniques often is not successful, but recent advances promise a brighter
      future.

PMID- 9019367
TI  - Confessions of a pharmacy thief.

PMID- 9019368
TI  - Do we have optimal screening limits in Sweden for vision testing at the age of 4
      years?
AB  - The purpose of this study was to evaluate the Swedish screening criteria for
      referral of children to ophthalmic care after visual acuity testing at the age of
      4 years. The screening limit has generally been 0.8. To what extent do children
      with 0.65 in each eye (0.65/0.65) or 0.65 in one and 0.8 in the other (0.65/0.8)
      at the age of 4 years have visual defects needing early treatment? Sixty-three
      children who had failed screening underwent orthoptic and ophthalmologic
      evaluation. Twenty-four patients (38%) saw 0.65/0.65 or 0.65/0.8 and were studied
      further. None of them had manifest strabismus. Refractive errors were minor
      except in 2 patients who had significant hyperopia. Twenty-two of these 24
      patients returned for reevaluation at the age of five years and that time 18 of
      them saw 0.8 or more without treatment. Our findings suggest that children with
      visual acuity of no less than 0.65 and no more than one line's difference between
      the eyes at 4 years of age seldom have visual defects needing treatment.

PMID- 9019369
TI  - Handedness in strabismics. Etiological implications.
AB  - The incidence of non right handedness was found to be significantly higher in a
      group of 228 strabismics when compared with a control group of neurologically
      normal non strabismic subjects. The difference was still present after
      elimination of strabismics with known neurological or general health problems, or
      who were born prematurely. The strabismics showed no inter group differences in
      handedness in relation to the type of retinal correspondence present or the
      ability to achieve normal or abnormal binocular single vision. Evidence is
      reviewed for the presence of a developmental defect leading to strabismus, and
      results of this survey support a previously proposed idea that a developmental
      defect leads to strabismus, the type of which reflects the severity of the defect
      (although external factors may also be an influence).

PMID- 9019370
TI  - Proliferating cell nuclear antigen colocalization with corneal epithelial stem
      cells and involvement in physiological cell turnover.
AB  - Corneal integrity is dependent on a constant turnover of epithelial cells.
      According to the current hypothesis essential contributors to this process, the
      so-called stem-cells, are localized in the limbal area of the cornea. However,
      histological identification of stem cells of the cornea is thus far not possible.
      In the present study we have used specific antibodies against proliferating cell
      nuclear antigen (PCNA). The nuclear protein is expressed in cells during
      replication. Prior to establishment of staining indices the optimal fixation
      procedure was found to be of major importance for the results and standardized
      for fixation in 4% formaldehyde. This procedure also gave the best preservation
      of the morphology. In the corneas of ten New Zealand rabbits the staining index
      for PCNA was found to be on average 23% (SD +/- 13%) for the basal layer of the
      limbal epithelium. In the mid-peripheral and central corneal epithelium only
      occasional staining of PCNA was detected with a 2% staining index (SD +/- 2%).
      The agglomeration of PCNA-positive cells in the basal layer of the limbal
      epithelium together with their colocalization with the known location of stem
      cells strongly suggests that PCNA could serve as a reliable indicator for the
      proximity of proliferating corneal epithelial stem cells in histological
      sections, which would be of significant clinical importance.

PMID- 9019371
TI  - Early cell kinetic effects of some drugs on the rat corneal and conjunctival
      epithelia.
AB  - The early cell kinetic response in the rat corneal and conjunctival epithelia was
      studied after a single topical application of dipivefrine, adrenaline and timolol
      with and without benzalkonium chloride. Benzalkonium chloride alone in different
      concentrations, 0.004%, 0.01%, 0.02% and 0.04%, respectively, was also evaluated.
      The stathmokinetic method and the tritiated thymidine technique were used to
      estimate the mitotic rate and the labelling index. Dipivefrine (Propine) gave a
      significant depression of the mitotic rate almost to the same extent as
      adrenaline in the corneal epithelium, whereas no changes were found in the limbal
      area and in the conjunctiva. Timolol (Oftan) with or without benzalkonium
      chloride, and benzalkonium chloride in different concentrations gave no obvious
      changes of the mitotic rate. No distinct drug effects on the labelling index were
      observed.

PMID- 9019372
TI  - Observation of precorneal tear film in patients with Sjogren's syndrome.
AB  - The present study was designed to examine whether the lipid layer of the
      precorneal tear film has a role in the pathogenesis of dry eye. The study
      involved 104 eyes of 52 patients with primary Sjogren's syndrome. The lipid layer
      of the precorneal tear film was observed by non-contact specular microscopy, and
      relationships between grade of interference color and the tear function
      parameters were examined. The lipid layer was classified from Grade 1, with no
      interference color, to Grade 4, of most intense interference color. In addition
      to these four grades, an oil droplet type not previously described was
      characterized. The grade of interference color was closely related to the
      intensity of vital staining. The oil droplet type was associated with more severe
      ocular surface damage than were Grades 1 through 4. The findings of this study
      suggest that the state of the lipid layer of the tear film may have some
      involvement in the pathogenesis of dry eye.

PMID- 9019373
TI  - Soft lens movement: effect of blink rate on lens settling.
AB  - Little is understood about the mechanism by which soft lenses settle on the eye,
      although it has been suggested that lens base curve, steepening with in-eye lens
      dehydration or tear film changes may influence lens movement in the initial
      period of wear. In this study, we investigated the role of postlens tear fluid
      expulsion by assessing lens movement in 20 subjects wearing 38% water content
      hydrogel lenses for 10 min under three different conditions: 10 blinks/min, 30
      blinks/min and eye closure. Over the 10 min wearing period, the total decrease in
      median lens movement for the 10 blinks/min condition was 0.07 mm, which was not a
      significant change (Friedman ANOVA, p = 0.13), while significant decreases
      occurred with conditions of 30 blinks/min (0.19 mm, p = 0.004) and eye closure
      (0.43 mm, p = 0.0001). As expected, lens movement under the three conditions was
      the same at insertion, but was significantly higher thereafter for the slower
      blink rate condition compared to the faster blink rate or eye closure conditions
      (Wilcoxon test, Z = 2.8 and -3.0, p = 0.006 and 0.003, respectively). Based on
      these findings, we postulate the model that the extent of lens settling and the
      degree of postinsertion lens movement are determined by the timeaverage pressure
      for postlens tear film expulsion exerted on the lens by the eyelids.

PMID- 9019374
TI  - Vasomotor nerves of vessels in the human optic nerve.
AB  - Aminergic and cholinergic vasomotor nerves in vessels of the human optic nerve
      were studied morphologically. Aminergic nerve fibers were observed by the
      glyoxylic acid method. Cholinergic nerve fibers were observed by light microscopy
      after acetylcholinesterase staining by the Karnovsky-Roots method and Tago's
      modified method. In the retrobulbar optic nerve behind the bulbus, aminergic and
      cholinergic vasomotor nerves were observed to be dense in the central retinal
      artery and vein and posterior ciliary arteries. A large number of vasomotor
      nerves were also demonstrated in vessels in the septum of the optic nerve, but
      they were sparse in pial vessels. Further centrally, a few vasomotor nerves were
      found in pial vessels of the intracanalicular and intracranial optic nerve, but
      few were observed in the septum of the optic nerve. At the optic chiasm they were
      densely distributed in pial vessels.

PMID- 9019375
TI  - Neuropeptide Y (NPY) in the orbital arteries of the rabbit. Immunocytochemistry
      and vasomotor activity.
AB  - The purpose of the present study was to investigate the presence and vascular
      effects of neuropeptide Y in the rabbit orbital arteries. Neuropeptide Y
      containing nerve fibers were demonstrated, using an indirect immunofluorescence
      method with a neuropeptide Y antiserum raised in goat against porcine
      neuropeptide Y. Isometric responses in isolated circular segments of the orbital
      arteries were measured following application of neuropeptide Y, different
      contracting agonists, and the neuropeptide Y blocker alpha-trinositol. A rich
      supply of neuropeptide Y-containing nerve fibers was seen around the orbital
      arteries. Neuropeptide Y (10(-10)-10(-6) M) did not induce any contractions in
      resting arterial segments. Noradrenaline and histamine evoked concentration
      dependent constrictions which were potentiated by neuropeptide Y (3 x 10(-7) M).
      This potentiation was completely blocked by alpha-trinositol (3 x 10(7) M). The
      contractile effects of endothelin-1, endothelin-3, prostaglandin F2 alpha, and 5
      hydroxytryptamine were not modified by neuropeptide Y.

PMID- 9019376
TI  - A comparative study of intraocular irrigating solutions: effects on
      electroretinography readings during closed vitrectomy in humans.
AB  - The effects of intraocular irrigating solutions on electroretinography have been
      extensively studied in animal models, but effects on human electroretinography
      have not been reported. This study examined the effects of two commercially
      available irrigating solutions, S-MA2 (Opeguard MA) and DE-057 (BBS-Plus) on 30
      Hz flicker electroretinography during closed vitrectomy in humans. Eight eyes of
      8 patients were examined. All patients underwent a simple vitrectomy without
      treatment of proliferative membrane. For 30-Hz flicker electroretinography
      recording, a contact lens with a built-in light-emitting diode was sterilized and
      used as both a stimulus source and a recording electrode. Replacing S-MA2 with DE
      057 decreased the electroretinography amplitude from 55.8 +/- 15.2 to 45.5 +/-
      13.2 microV (mean +/- SEM). Changing the irrigation solution from DE-057 back to
      S-MA2 increased the amplitude from 45.5 +/- 13.2 to 59.9 +/- 17.3 microV.
      However, these changes were not statistically significant. Replacing S-MA2 with
      DE-057 significantly increased the peak time from 50.1 +/- 1.5 to 57.6 +/- 1.3
      msec (p < 0.001). This change was reversible; after changing from DE-057 back to
      S-MA2, the peak time of flicker electroretinography significantly decreased from
      57.6 +/- 1.3 to 49.0 +/- 2.1 msec (p < 0.01). Thus intraoperative 30-Hz
      electroretinography showed delayed peak time during irrigation with DE-057, as
      compared with S-MA2. The lower potassium concentration and higher glucose
      concentration of S-MA2, as compared with DE-057, may be the cause of such
      electroretinography changes.

PMID- 9019377
TI  - Screening for diabetic retinopathy. Initiation and frequency.
AB  - A screening program for diabetic eye disease was established in Iceland in 1980.
      Diabetics involved in the screening program have a low prevalence of blindness,
      1% in type 1 and 1.6% in type 2. We examined ways to make the screening program
      more efficient by identifying subgroups at low risk of developing eye disease
      that require treatment and therefore need less frequent screening. We studied
      whether diabetic eye disease screening programs may be trimmed by excluding
      children and examining diabetics without retinopathy biannually. Our results
      indicate that diabetic children under the age of 12 years do not need regular
      screening for eye disease. Biannual examinations seem to suffice in type 1 and 2
      diabetic patients without retinopathy. However, in a setting where the eye clinic
      is located apart from the diabetes clinics, biannual examinations present
      practical problems which could result in a less effective screening for diabetic
      eye disease.

PMID- 9019378
TI  - Quenching of UV-induced fluorescence by ascorbic acid in the aqueous humour.
AB  - Spectrophotometry and spectrofluorimetry of bovine aqueous humour have been
      performed. The question of whether mechanisms for fluorescence quenching exist in
      the eye media was evaluated. It turned out that the marked fluorescence of
      tryptophane and protein was considerably quenched by the ascorbic acid, an
      observation not shown before. Thus, the aqueous humour minimizes UV-radiation to
      the lens in diurnal animals through three different mechanisms: 1) Absorption. 2)
      Fluorescence-quenching. 3) Fluorescence-mediated ray transformation of energy
      rich short wavelengths to less potent longer wave-lengths. The impact of each of
      them is significantly influenced by the ascorbate concentration in the aqueous
      humour. The phenomenon of fluorescence-mediated ray transformation is, of course,
      per se independent of ascorbate, but the transformational input is significantly
      reduced due to ascorbate.

PMID- 9019379
TI  - Diurnal change of anterior chamber depth in rabbits.
AB  - It has been shown that there is a circadian rhythm of intraocular pressure and
      aqueous humor flow in rabbits. It has also been shown that there is a fluctuation
      in the volume of the aqueous that can be aspirated from the anterior chamber at
      different times of day. This finding would suggest that the depth and volume of
      the anterior chamber of this species also undergoes a circadian rhythm. To
      confirm this hypothesis, we measured by pachometry the anterior chamber depth in
      11 adult New Zealand albino rabbits that had been conditioned to light from 6
      a.m. to 6 p.m. and to dark from 6 p.m. to 6 a.m. The measurements were performed
      at noon and at midnight. The anterior chamber was found to be 4% deeper at
      midnight than at noon (p < 0.001). This finding suggests that the volume of the
      anterior chamber would be slightly larger at night than during the day in the
      rabbit eye. We have no explanation for this finding. However, the difference is
      too small to have an appreciable effect on the measurement of aqueous dynamics or
      pharmaceutical effects.

PMID- 9019380
TI  - The quantitative effect of Healon on early postoperative intraocular pressure
      after extracapsular cataract extraction with implantation of a posterior chamber
      lens.
AB  - In a prospective, randomized and masked study the quantitative effect of sodium
      hyaluronate (Healon) on early postoperative intraocular pressure after cataract
      surgery was evaluated. At the end of planned extracapsular cataract extraction
      with implantation of posterior chamber lens, 0.1 ml or 0.2 ml of Healon was
      injected into the anterior chamber. The intraocular pressure was measured
      preoperatively, 3-6 h and 24 h postoperatively. All patients received topical
      timolol at the end of surgery. The results were compared to eyes operated with
      identical techniques where Healon was aspirated at the end of surgery. Three to
      six hours postoperatively a significant drop in mean intraocular pressure from
      preoperative pressure occurred when Healon was aspirated, but no statistical
      differences in mean intraocular pressure appeared when 0.1 ml or 0.2 ml of Healon
      was injected. The frequencies of pressure rise above 30 mmHg show no differences
      among the groups. Twenty-four hours postoperatively a significant pressure
      elevation from mean preoperative pressure occurred when 0.1 ml or 0.2 ml Healon
      was injected compared to the group were Healon was aspirated at the end of
      surgery. Similar results are seen when pressure rise above 30 mmHg are concerned.

PMID- 9019381
TI  - Bilateral surgery.

PMID- 9019382
TI  - Bilateral simultaneous trabeculectomy. A review of outcome and a survey of
      ophthalmologists' attitudes.
AB  - In this study the attitudes of experienced ophthalmologists to bilateral
      simultaneous trabeculectomy were canvased using a postal questionnaire. Only 16%
      of respondents ever performed bilateral simultaneous trabeculectomy (BST). The
      main reason for not performing BST was fear of bilateral simultaneous
      complications. The notes of 95 patients who had undergone BST were reviewed. Post
      operative complications occurred in 41 eyes (43.6%) during the first post
      operative week, but only 8 patients (8.5%) hand complications in both eyes. At 3
      months post-operatively, 5 patients (5.5%) had bilateral raised intraocular
      pressures with or without medication, and at 12 months this figure was 8 patients
      (9.3%). Twenty patients (21.3%) had a drop in visual acuity of two Snellen lines
      or more in both eyes at one week. At 3 months this figure was 5 patients (5.5%),
      and at 12 months 3 patients (3.5%) had lost two or more lines of vision in both
      eyes. Although BST is not commonly performed, the incidence of bilateral post
      operative complications is low.

PMID- 9019383
TI  - External radiotherapy for circumscribed choroidal haemangiomas using a modified
      retinoblastoma technique.
AB  - This report describes two cases of circumscribed choroidal haemangiomas involving
      the fovea, complicated by serous retinal detachment. Laser photocoagulation,
      generally accepted as the treatment of choice for choroidal haemangioma, was
      considered either to be of no visual benefit or a risk for jeopardizing vision
      further due to the subfoveolar lesions. Fractionated radiotherapy using a lens
      sparing, modified retinoblastoma technique, was given, using circular fields of
      15 mm diameter. The dose was 24 Gy in 8 fractions. In both eyes the retina
      reattached completely. The visual acuity improved markedly in the first, and was
      restored to the prior level in the second. Normalization of a high intraocular
      pressure was also achieved in the second case. We believe this method to be a
      reasonable and effective therapy for some choroidal haemangiomas after careful
      individual consideration.

PMID- 9019384
TI  - Penetrating keratoplasty and transscleral fixation of posterior chamber lens.
AB  - We reviewed the charts of 21 patients who underwent penetrating keratoplasty and
      transscleral fixation of a posterior chamber lens. One lens was sutured in an
      aphakic eye and 20 lenses were sutured after removal of an anterior chamber lens.
      Postoperative follow-up averaged 13 months (2-39 months). Visual acuity improved
      in 20 patients (95%) and remained the same in 1 patient (5%). Postoperative
      visual acuity was less than 0.1 in 5 patients (23.8%), 0.1 to 0.33 in 14 patients
      (66.7%) and better than 0.33 in 2 patients (9.5%). Twelve patients (57.1%)
      expressed a substantial reduction in ocular pain, 7 patients (33.3%) had no pain
      either before or after the operation, 2 patients (9.5%) expressed no reduction in
      pain. No cases of endophthalmitis, choroidal hemorrhage or retinal detachment
      were found. In one case, the sutured lens was dislocated without disturbing
      vision. Intraocular pressure increased in 3 of 9 patients with preoperative
      glaucoma. New-onset glaucoma developed in 1 patient. We find transscleral
      fixation of a posterior chamber lens to be an acceptable procedure in penetrating
      keratoplasty with IOL implantation where capsular support is inadequate for
      conventional implantation of a posterior chamber lens.

PMID- 9019385
TI  - Features of the partially expanded human inferior conjunctival sac.
AB  - Space in the inferior conjunctival sac has not been studied in sufficient detail
      to allow optimal physical design of conjunctival inserts. We analyzed shape and
      volume of partially expanded, anesthetized, left inferior conjunctival sacs in 10
      young adult subjects by injection of a liquid polysiloxane molding compound. Mean
      volume, greatest thickness, central thickness, horizontal width, and vertical
      height of 60 molds were 125.7 microliters (SD = 55), 1.56 mm (SD = 0.69), 1.46 mm
      (SD = 0.62), 20.7 mm (SD = 2.2), and 8.9 mm (SD = 0.8), respectively. Volumetric
      and linear dimensions varied between subjects, but certain features were common
      to all molds: 1) a crescent shape horizontally; 2) a thick inferior horizontal
      ridge; and 3) a wedge-like shape sagittally. We postulate several advantages of
      conjunctival inserts with features representative of our molds of conjunctival
      sacs, e.g. such inserts may be more comfortable, less expelled, larger in volume,
      and contact more tissue area.

PMID- 9019386
TI  - Mycotic keratitis by Fusarium moniliforme.
AB  - We report on a case of keratitis with hypopion by Fusarium monilinforme, in a
      patient with palpebral retraction and light exophthalmos caused by
      hyperthyroidism. We emphasize the importance of the microscopic examination of
      bioptic material and the identification of fungal species: the first permits an
      early diagnosis, the second the adoption of a targeted and effective therapy. In
      our case, the ocular infection was successfully treated with antimycotic drugs
      used topically.

PMID- 9019387
TI  - Comparison of etidocaine and bupivacaine + lidocaine in retrobulbar anaesthesia.
AB  - Etidocaine (15 mg/ml) was compared with bupivacaine (5 mg/ml) combined with
      lidocaine (10 mg/ml) in retrobulbar anaesthesia. One hundred and twelve patients
      were randomised into two groups. Supplemental anaesthesia was needed in 41% of
      cases of the etidocaine group and 32% of the bupivacaine-lidocaine group.
      Akinesia was evaluated by the surgeon both pre- and postoperatively and was found
      to be good or complete in more than 95% of both groups. Recovery from the motor
      and sensory block was investigated three times during the first 24 postoperative
      hours. The motor block of the orbicular muscle disappeared earlier than that of
      the globe. Akinesia lasted significantly longer in the etidocaine group than in
      the bupivacaine-lidocaine group: after 14 h 69% vs 100%, respectively, of the
      eyes showed normal movements. Sensation in the cornea was also regained more
      rapidly in patients treated with the mixture.

PMID- 9019388
TI  - Clinical usefulness of biopsy in giant cell arteritis.
AB  - To evaluate the diagnostic usefulness of temporal artery biopsy in the diagnosis
      of giant cell arteritis, the clinical records of 98 patients who underwent this
      procedure between 1984 and 1992 were reviewed. The biopsies were positive for
      giant cell arteritis in 13 (13%) cases. In addition, 9 patients with negative
      biopsy were considered to have giant cell arteritis based on clinical
      examination, while 76 patients had other diagnoses. About 90% of the patients
      with giant cell arteritis were women. Evaluating the clinical features and
      laboratory findings, a history of headache, a combination of headache and the
      erythrocyte sedimentation rate > 40 mm/h and a combination of headache and
      temporal tenderness were significantly more common among patients with positive
      diagnosis than among the other patients.

PMID- 9019389
TI  - A spider hits the eye.
AB  - To determine the necessary medical care and permanent ocular damage of a
      particular type of preventable ocular trauma, an observational study of 22
      patients referred to the University Hospital Nijmegen (1983-1993) with eye
      injuries caused by the accidental release of tightened elastic straps of the so
      called "spider' design was performed. Although the traumatized eyes of the 22
      patients could be saved from blindness by extensive medical and surgical
      treatment in the majority of cases, 13 patients (59%) had residual permanent
      visual impairment (visual acuity < or =6/10, or aphakia) at the end of the follow
      up period. Three of them had lost the perception of light in the involved eye;
      one painful blind eye had to be removed. It is concluded that elastic straps with
      free-end metal hooks should not be used to secure luggage because of the
      potential risk of irreversible damage to the eye.

PMID- 9019390
TI  - The Schirmer test with topical anaesthesia. A latent learning effect?

PMID- 9019391
TI  - Papers presented at International Novo Nordisk Symposium on Growth. Santiago de
      Compostela, Spain, October 1995.

PMID- 9019392
TI  - Asthma among the famous. Augustus Frederick (1773-1843), British Duke of Sussex.

PMID- 9019393
TI  - Asthma among the famous. John Bostock (1773-1846), British physician and
      medicinal chemist.

PMID- 9019394
TI  - Asthma among the famous. Rene Theophile-Hyacinthe Laennec (1781-1826), French
      physician.

PMID- 9019395
TI  - Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise?

PMID- 9019396
TI  - Cyclin/Cdk-dependent initiation of DNA replication in a human cell-free system.
AB  - We describe a cell-free system from HeLa cells that initiates DNA replication
      under cell cycle control. G1 but not G2 phase nuclei initiate replication when
      coincubated with S phase nuclei in cytosolic extracts from S phase but not from
      G1 or G2 phase HeLa cells. S phase nuclei or an S phase nuclear extract are
      required for the initiation of semiconservative DNA replication in G1 nuclei but
      not for elongation in S phase nuclei. S phase nuclear extract could be replaced
      by recombinant human cyclins A and E complexed to Cdk2 but not by Cdk2 alone or
      by human cyclin B1 complexed to Cdc2. In S phase cytosol, cyclins A/Cdk2 and
      E/Cdk2 triggered initiation synergistically.

PMID- 9019397
TI  - Redox signal transduction: mutations shifting [2Fe-2S] centers of the SoxR sensor
      regulator to the oxidized form.
AB  - SoxR is a [2Fe-2S] transcription factor triggered by oxidative stress and
      activated in vitro by one-electron oxidation or assembly of the iron-sulfur
      centers. To distinguish which mechanism operates in cells, we studied
      constitutively active SoxR (SoxRc) proteins. Three SoxRc proteins contained [2Fe
      2S] centers required for in vitro transcription and, like wild-type SoxR, were
      inactivated by chemical reduction. However, in vivo spectroscopy showed that even
      without oxidative stress, the three SoxRc proteins failed to accumulate with
      reduced [2Fe-2S] (< or = 4% compared to > or = 40% for wild type). One SoxRc
      protein had a redox potential 65 mV lower than wild type, consistent with its
      accumulation in the oxidized (activated) form in vivo. These results link in
      vitro and in vivo approaches showing novel redox regulation that couples an iron
      sulfur oxidation state to promoter activation.

PMID- 9019398
TI  - Vertebrate embryonic cells will become nerve cells unless told otherwise.

PMID- 9019399
TI  - Targeted disruption of the melanocortin-4 receptor results in obesity in mice.
AB  - The melanocortin-4 receptor (MC4-R) is a G protein-coupled, seven-transmembrane
      receptor expressed in the brain. Inactivation of this receptor by gene targeting
      results in mice that develop a maturity onset obesity syndrome associated with
      hyperphagia, hyperinsulinemia, and hyperglycemia. This syndrome recapitulates
      several of the characteristic features of the agouti obesity syndrome, which
      results from ectopic expression of agouti protein, a pigmentation factor normally
      expressed in the skin. Our data identify a novel signaling pathway in the mouse
      for body weight regulation and support a model in which the primary mechanism by
      which agouti induces obesity is chronic antagonism of the MC4-R.

PMID- 9019400
TI  - The TSG101 tumor susceptibility gene is located in chromosome 11 band p15 and is
      mutated in human breast cancer.
AB  - Recent work has identified a mouse gene (tsg101) whose inactivation in
      fibroblasts results in cellular transformation and the ability to produce
      metastatic tumors in nude mice. Here, we report that the human homolog, TSG101,
      which we isolated and mapped to chromosome 11, bands 15.1-15.2, a region proposed
      to contain tumor suppressor gene(s), is mutated at high frequency in human breast
      cancer. In 7 of 15 uncultured primary human breast carcinomas, intragenic
      deletions were shown in TSG101 genomic DNA and transcripts by gel and sequence
      analysis, and mutations affecting two TSG101 alleles were identified in four of
      these cancers. No TSG101 defects were found in matched normal breast tissue from
      the breast cancer patients. These findings strongly implicate TSG101 mutations in
      human breast cancer.

PMID- 9019401
TI  - Arrangement of tRNAs in pre- and posttranslocational ribosomes revealed by
      electron cryomicroscopy.
AB  - The three-dimensional structure of the translating 70S E. coli ribosome is
      presented in its two main conformations: the pretranslocational and the
      posttranslocational states. Using electron cryomicroscopy and angular
      reconstitution, structures at 20 A resolution were obtained, which, when compared
      with our earlier reconstruction of "empty" ribosomes, showed densities
      corresponding to tRNA molecules--at the P and E sites for posttranslocational
      ribosomes and at the A and P sites for pretranslocational ribosomes. The P-site
      tRNA lies directly above the bridge connecting the two ribosomal subunits, with
      the A-site tRNA fitted snugly against it at an angle of approximately 50 degrees,
      toward the L7/L12 side of the ribosome. The E-site tRNA appears to lie between
      the side lobe of the 30S subunit and the L1 protuberance.

PMID- 9019402
TI  - Conformation-independent binding of monoglucosylated ribonuclease B to calnexin.
AB  - Calnexin is a membrane protein of the endoplasmic reticulum that associates
      transiently with newly synthesized N-linked glycoproteins in vivo. Using defined
      components, the binding of ribonuclease B (RNase B) Man7-Man9 glycoforms to the
      luminal domain of calnexin was observed in vitro only if RNase B was
      monoglucosylated. Binding was independent of the conformation of the
      glycoprotein. Calnexin protected monoglucosylated RNase B from the action of
      glucosidase II and PNGase F but not from that of Endo H, which completely
      released the protein from calnexin. These observations directly demonstrate that
      calnexin can act exclusively as a lectin.

PMID- 9019403
TI  - Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton
      linkages.
AB  - To move forward, migrating cells must generate traction forces through surface
      receptors bound to extracellular matrix molecules coupled to a rigid structure.
      We investigated whether cells sample and respond to the rigidity of the anchoring
      matrix. Movement of beads coated with fibronectin or an anti-integrin antibody
      was restrained with an optical trap on fibroblasts to mimic extracellular
      attachment sites of different resistance. Cells precisely sense the restraining
      force on fibronectin beads and respond by a localized, proportional strengthening
      of the cytoskeleton linkages, allowing stronger force to be exerted on the
      integrins. This strengthening was absent or transient with antibody beads, but
      restored with soluble fibronectin. Hence, ligand binding site occupancy was
      required. Finally, phenylarsine oxide inhibited strengthening of cytoskeletal
      linkages, indicating a role for dephosphorylation. Thus, the strength of integrin
      cytoskeleton linkages is dependent on matrix rigidity and on its biochemical
      composition. Matrix rigidity may, therefore, serve as a guidance cue in a process
      of mechanotaxis.

PMID- 9019404
TI  - Ca2+ flow via tunnels in polarized cells: recharging of apical Ca2+ stores by
      focal Ca2+ entry through basal membrane patch.
AB  - Intracellular Ca2+ store depletion induces Ca2+ entry across the plasma membrane,
      allowing the store to recharge. In our experiments, Ca2+ stores in pancreatic
      acinar cells were depleted by acetylcholine (ACh) stimulation in Ca2+-free
      solution. Thereafter, Ca2+ entry was only allowed through a CaCl2-containing
      pipette attached to the basal membrane. Recharging intracellular Ca2+ stores via
      a patch pipette occurred without a rise in the cytosolic Ca2+ concentration and
      depended on the operation of a thapsigargin-sensitive Ca2+ pump. After a period
      of focal Ca2+ entry, ACh could again evoke a rise in the cytosolic Ca2+
      concentration, and this rise always started in the apical secretory pole.
      Recharging the apical Ca2+ store therefore depends on Ca2+ flow through a tunnel
      from the basal to the secretory pole, and the endoplasmic reticulum Ca2+ pump is
      essential for this process.

PMID- 9019405
TI  - It's prime time for reverse transcriptase.

PMID- 9019406
TI  - The Arabidopsis NPR1 gene that controls systemic acquired resistance encodes a
      novel protein containing ankyrin repeats.
AB  - The Arabidopsis NPR1 gene controls the onset of systemic acquired resistance
      (SAR), a plant immunity, to a broad spectrum of pathogens that is normally
      established after a primary exposure to avirulent pathogens. Mutants with defects
      in NPR1 fail to respond to various SAR-inducing treatments, displaying little
      expression of pathogenesis-related (PR) genes and exhibiting increased
      susceptibility to infections. NPR1 was cloned using a map-based approach and was
      found to encode a novel protein containing ankyrin repeats. The lesion in one
      npr1 mutant allele disrupted the ankyrin consensus sequence, suggesting that
      these repeats are important for NPR1 function. Furthermore, transformation of the
      cloned wild-type NPR1 gene into npr1 mutants not only complemented the mutations,
      restoring the responsiveness to SAR induction with respect to PR-gene expression
      and resistance to infections, but also rendered the transgenic plants more
      resistant to infection by P. syringae in the absence of SAR induction.

PMID- 9019407
TI  - A stable RAG1-RAG2-DNA complex that is active in V(D)J cleavage.
AB  - The RAG1 and RAG2 proteins initiate V(D)J recombination by making specific double
      strand DNA breaks at recombination signal sequences. We show here that RAG1 and
      RAG2 bind specifically to this sequence, forming a stable protein-DNA complex.
      The complex requires the conserved heptamer and nonamer motifs of the
      recombination signal as well as both the RAG1 and RAG2 proteins. This complex is
      able to either nick or form hairpins at the V(D)J signal sequence, depending on
      the divalent cation present. A complex trapped using Ca2+ is subsequently active
      when transferred to Mg2+ or Mn2+. After cleavage, the complex is destabilized and
      the RAG proteins dissociate. We term this early precursor in the V(D)J
      recombination reaction a "stable cleavage complex."

PMID- 9019408
TI  - Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic
      obliteration leads to endocrine disorders in Cpe(fat) mice.
AB  - A proposed mechanism for sorting secretory proteins into granules for release via
      the regulated secretory pathway in endocrine-neuroendocrine cells involves
      binding the proteins to a sorting receptor at the trans-Golgi network, followed
      by budding and granule formation. We have identified such a sorting receptor as
      membrane-associated carboxypeptidase E (CPE) in pituitary Golgi-enriched and
      secretory granule membranes. CPE specifically bound regulated secretory pathway
      proteins, including prohormones, but not constitutively secreted proteins. We
      show that in the Cpe(fat) mutant mouse lacking CPE, the pituitary prohormone, pro
      opiomelanocortin, was missorted to the constitutive pathway and secreted in an
      unregulated manner. Thus, obliteration of CPE, the sorting receptor, leads to
      multiple endocrine disorders in these genetically defective mice, including
      hyperproinsulinemia and infertility.

PMID- 9019409
TI  - Binding of secretory precursor polypeptides to a translocon subcomplex is
      regulated by BiP.
AB  - The translocation of a secretory precursor protein across the ER membrane
      comprises three phases: docking of the precursor at the membrane, insertion into
      the translocation pore, and exit from the pore into the ER lumen. We demonstrate
      that Sec62p, Sec71p and Sec72p form a translocon subcomplex that engages
      secretory precursors at the membrane site of the ER translocation machinery.
      Binding of a precursor to the subcomplex depends on the presence of an intact
      signal sequence and occurs only in the absence of ATP. In the presence of ATP,
      the precursor is released from the subcomplex in a reaction mediated by the
      lumenal hsp70, BiP. This release reaction, which is specific to BiP and requires
      interaction between BiP and the DnaJ homolog Sec63p, defines a role for BiP and
      Sec63p early in the ER translocation process.

PMID- 9019410
TI  - Secreted fringe-like signaling molecules may be glycosyltransferases.

PMID- 9019411
TI  - A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear
      pore complex protein RanBP2.
AB  - We have found that the mammalian Ran GTPase-activating protein RanGAP1 is highly
      concentrated at the cytoplasmic periphery of the nuclear pore complex (NPC),
      where it associates with the 358-kDa Ran-GTP-binding protein RanBP2. This
      interaction requires the ATP-dependent posttranslational conjugation of RanGAP1
      with SUMO-1 (for small ubiquitin-related modifier), a novel protein of 101 amino
      acids that contains low but significant homology to ubiquitin. SUMO-1 appears to
      represent the prototype for a novel family of ubiquitin-related protein
      modifiers. Inhibition of nuclear protein import resulting from antibodies
      directed at NPC-associated RanGAP1 cannot be overcome by soluble cytosolic
      RanGAP1, indicating that GTP hydrolysis by Ran at RanBP2 is required for nuclear
      protein import.

PMID- 9019412
TI  - Proceedings of the 2nd Polish-German Symposium in Nephrology and Hypertension.
      Wisla, Poland, May 11-13, 1995.

PMID- 9019413
TI  - Case of plagiarism. Work originating from Denmark, translated into Polish and
      published in a Polish journal. Four Polish scientists guilty of scientific
      dishonesty. The Danish Committee on Scientific Dishonesty.

PMID- 9019415
TI  - Proceedings of the IInd National Meeting of the Hellenic Society of
      Gynaecological Oncology. Delphi, October 6-8, 1995.

PMID- 9019414
TI  - A 5-year (1990-1994) neuroblastoma screening feasibility study in France.
      Methodology and preliminary observations.
AB  - INTRODUCTION: Following the pioneering Japanese experience, several European and
      North American groups implemented pilot studies on screening infants for
      neuroblastoma, considering the possibility of demonstrating a decrease in
      mortality rate. In France, a 5-year (1990-1994) feasibility study on
      neuroblastoma screening at the age of 4 months was initiated in the Rhone
      district (1.5 M inhabitants, 26,000 births per year). METHODS: Vanillylmandelic
      (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by
      the Jaffe's kinetic method on Technicon RA-XT. VMA and HVA were expressed as
      microgram/mg of Cr. The method was assessed with both a daily intra-laboratory
      control and a sample of urine obtained from a national quality control organism.
      RESULTS AND DISCUSSION: The overall participation rate for the 5-year period was
      82.2%. Out of 105,293 infants tested from 128,126 births, 12 NB cases were
      discovered with screening (screened cases) and 1 case was discovered with a late
      performed test (at 13 months of age). Six neuroblastomas were found clinically
      before the age of 4 m. Two cases were missed because the parents did not perform
      the test. Three children with normal tests at screening were false-negative
      cases: two of them were found secreting at diagnosis, while one remained non
      secretory at diagnosis and later on. Otherwise, thirty-five false-positive tests
      were found. Biochemical observations are discussed. It is too early to reach
      clinical conclusions from this screening program on neuroblastomas as it is
      presently being followed up.

PMID- 9019416
TI  - [Influence of the velocity of meal ingestion on postprandial glycemia].
AB  - To assess the influence of the velocity of meal ingestion on postprandial
      glycemia, 10 healthy volunteers and 10 patients with non-insulin-dependent
      diabetes mellitus (NIDDM) were studied. All the subjects had two identical meals
      (1980 J, carbohydrate 37%, proteins 23%, lipids 40%) on different days. One meal
      was ingested in 10 minutes (fast ingestion) while the other was ingested in 20
      minutes (slow ingestion). Glucose serum levels were measured immediately before
      the meal and throughout the following 180 minutes. In NIDDM patients, serum
      glucose levels from 30 to 90 minutes were significantly (p < 0.05) higher after
      fast ingestion than after the slow intake. Area under the glucose curve (AUC) and
      maximal peak of serum glucose concentrations (MP) showed also higher values with
      fast intake: AUC was of 13 +/- 2.4 and 11.3 +/- 2.9 mmol/ L/h (X +/- SD) (p <
      0.05), MP 15.8 +/- 4.3 and 12.9 +/- 2.6 mmol/L (p < 0.05) with fast and slow
      ingestion respectively. No differences in serum glucose levels between test were
      noticed in healthy subjects. Slow meal ingestion might be a dietary
      recommendation in patients with NIDDM.

PMID- 9019417
TI  - [Juvenile myoclonic epilepsy].
AB  - Juvenile Myoclonic Epilepsy is an special type of epilepsy present in
      approximately 4 to 10% of patients with epilepsy. This disorder is characterized
      by an onset in the adolescence and by the presence of various types of
      generalized seizures: tonic-clonic, typical absences and myoclonic in patients
      with otherwise normal neuropsychological development. This form of epilepsy was
      described 30 years ago by Janz, and even today the diagnosis is seldom performed
      by the general physician as not well as by many neurologists and neurosurgeons.
      We studied Juvenile Myoclonic Epilepsy in 20 patients, underscoring its clinical
      and electroencephalographic profiles and its response to treatment, and
      established a comparison of these patients with other, existent in the medical
      literature. The goal of the present work is to call attention to this
      neurological disorder and to provide useful information for its adequate
      diagnosis and treatment.

PMID- 9019418
TI  - [Health, marginality and regional development].
AB  - The paper discusses the close link between marginality, regional development and
      health. In order to do so, reference is made to some health indicators like
      nutrition, causes of death and health infrastructure within the low as well as
      the high marginality areas. The paper also presents the strategies that the
      Ministry of Health has established to assist the population living in the high
      marginality areas. It specifies the related activities that are being carried out
      through the national institutes of health and the sanitary regulation offices.

PMID- 9019419
TI  - [Immunology in its century. Miguel F. Jimenez Conference, 1996].

PMID- 9019421
TI  - [Prelude to study of the history of surgery in Mexico and the United States in
      the 19th century].

PMID- 9019420
TI  - [Infections caused by enteropathogenic Escherichia coli].
AB  - Escherichia coli strains currently recognized to cause human diarrhea can be
      distinguished on the basis of pathogenic mechanism and separated into five
      categories: enterotoxigenic (ETEC), enteroinvasive (EIEC), enterohemorrhagic
      (EHEC), enteroaggregative (EAggEC) and enteropathogenic (EPEC). EPEC is a
      bacterial pathogen that causes diarrhea in infants, particularly in developing
      countries. The purpose of this review is to summarize recent advances in the
      understanding of EPEC pathogenesis and the contribution of Mexican investigators
      to the knowledge of this pathogen.

PMID- 9019422
TI  - [History of surgery in the United States in the 19th century].

PMID- 9019423
TI  - [Sir James Paget. Paget's disease and other contributions to medicine].

PMID- 9019424
TI  - [Intermittent pleural drainage by Dr. Don Ramon Macias (1885)].

PMID- 9019425
TI  - [Hydrosoluble contrast medium for bronchography. A Mexican priority. 1946].

PMID- 9019426
TI  - [Images of apoptosis].

PMID- 9019427
TI  - [Genes and human behavior].

PMID- 9019428
TI  - [Scorpion envenomation].

PMID- 9019429
TI  - [Emerging infectious diseases: reemerging and new].

PMID- 9019430
TI  - [Medical responsibility].

PMID- 9019431
TI  - [Recent advances in thrombophilia].

PMID- 9019432
TI  - viwish: a visualization server for protein modelling and docking.
AB  - A visualization tool viwish for proteins based on the Tcl command language has
      been developed. The system is completely menu driven and can display arbitrary
      many proteins in arbitrary many windows. It isinstantly t o use, even for non
      computer experts and provides possibilities to modify menus, configurations, and
      windows. It may be used as a stand-alone molecular graphics package or as a
      graphics server for external programs. Communications with these client
      applications is established even across different machines (through the send
      command to Tk, an extension of Tcl). In addition, a wide rage of chemical data
      like molecular surfaces and 3D gridded samplings of chemical features can be
      displayed. Therefore the systmen is especially useful for the development of
      algorithms that need visual distributed freely, including the source code.

PMID- 9019433
TI  - [HELLP syndrome. Severe consequence of hypertensive disease induced by
      pregnancy].
AB  - A descriptive, transversal retrospective study was performed, to determine the
      prevalence of HELLP syndrome among patients with Pregnancy-Induced Hypertension
      (PIH), who were admitted into the Gynecology and Obstetrics Service the American
      British Cowdray Hospital in Mexico City, since July 1992 to June 1995. We
      detected a total or 11 patients who had the diagnostic parameters proposed by
      Sibai, those were 11.8% of all the patients with PIH. The medial gestational age
      was 33 weeks (range from 30 to 39) The mean tensional levels were 170/ 107 mm Hg,
      in base of platelet count, nine patients were classified as Class I (82%) and two
      in Class II (18%), the medial peak levels of transaminases and bilirubins was
      reached 40 hours and that of lactic deshidrogenase 60 hours after the diagnosis
      was established, while the minimum levels of hematocrit and platelets were at 48
      and 57 respectively. The mean weight of the neonates was 1,655 g, the maternal
      mortality rate was 9% and the perinatal 8.3%, the diagnosis of HELLP syndrome was
      established before delivery in 40% of the cases and after that in 60%, puerperal
      HELLP may occur more frequently that is believed. Point out the importance of
      early detection of this clinic entity in order to establish an opportune and
      efficient treatment which improves maternal and fetal prognosis.

PMID- 9019434
TI  - [HELLP syndrome. Analysis of 102 cases].
AB  - One hundred and two cases of HELLP Syndrome admitted at the Adults Intensive Care
      Unit since January 1992, to June 1994; 63 with severe preeclampsia, 26 eclamptics
      and 13 with chronic hypertension more preeclampsia-eclampsia were analysed. The
      mean age was 24 year (range, 15 to 42). All 102 of the patients had one or more
      symptoms, those more often were: headache (85), right upper-quadrant tenderness
      (61), nausea and/or vomiting (31). The diastolic blood pressure maximum before
      the admission was 100 mm Hg or less in patients and 46 had more than 110 mm Hg.
      The mean platelets count was 58000 (range, 17000 to 100000). The median of
      laboratory test were: lactic dehydrogenase (830 u/l), glutamic oxaloacetic
      transaminase (278 u/l), glutamic pyruvic transaminase (263 u/l), total bilirubin
      (3.3 mg/dl). There were complications in 37 patients; acute renal failure 20,
      disseminated intravascular coagulopathy in 11, cerebral hemorrhage in 10 and
      abruption placentae in 6 patients. During the study period there were 20 death
      due to preeclampsia-eclampsia and 14 were in patients with HELLP syndrome,
      cerebral hemorrhage was the main cause (70%). In the group study 11 intrauterine
      deaths were diagnosed.

PMID- 9019435
TI  - [Laparoscopic treatment of dermoid cyst. First report in Mexico].
AB  - The laparoscopic treatment of adnexal masses has been controversial; however, the
      study of the case with the judicious use of the laboratory and ultrasound permit
      the laparoscopic approach of the most of the adnexal masses, including the
      dermoid cyst or mature cystic teratomas, and offer to the patient the benefits of
      the laparoscopic surgery with low morbidity. However, it should be do it in
      medical centers with the human and technics recourse need it for the performance.
      It present the first report in Mexico of laparoscopic treatment in contrast with
      a group of patients with laparotomy. The results of this study, are in conformity
      with the reports on the literature and suggest the initial laparoscopic approach
      of the dermoid cyst.

PMID- 9019436
TI  - [Current status of frequency and complications of pelvic exenterations for
      recurrent cervico-uterine cancer after radiation].
AB  - Frequency and morbimortality in pelvic exenterations for cervical cancer
      recurrent after radiation therapy at The Oncology Service, Hospital General de
      Mexico, SSA., are presented here. Between 1990 to 1994, seventy six patients with
      this diagnosis, were subjected to surgical exploration with the next findings:
      forty seven cases, (61.5%) had unresectable tumors; 29, (38.1%) were treated by
      exenterative procedures: Anterior exenterations, 14, (48.2%); Total
      exenterations, 13 (44.8%) and Posterior exenteration, 2 (6.8%). Tumor beyond
      pelvis was the common cause of unresectability in 34 cases, (72.2%) and
      periaortic lymph node metastases were related with this finding in 29 patients,
      (61.7%). Thirteen patients with pelvic exenterations, (44.8%) developed
      postoperative complications between 1 day and seven months after surgery. In
      seven cases, (24.1%) these complications were considered as minor complications
      and in six (20.6%) as major complications: Dehiscence of ureteral anastomosis,
      two cases, (-6.8%); ureterovaginal fistula, two (6.8%); small bowel obstruction,
      one (3.4%) and Chronic renal failure, one (3.4%). There were no postoperative
      deaths related to radical surgery in this series. It is concluded that the rate
      of laparotomies for cervical cancer recurrent after radiation therapy, have
      decreased in our Service, as compared to previous analysis as well as the rate of
      postoperative deaths from pelvic exenterations.

PMID- 9019437
TI  - [Hemorrhagic cystitis in pregnancy: report of a case and analysis of its
      treatment].
AB  - Hemorrhagic cystitis is generally a benign self-limited disorder, however there
      are some severe cases which are associated to a significant blood loss. The
      etiology may be either bacterial, viral or chemical in origin; though the cause
      is not identified in most of the cases. Immunocompromised patients or patients
      who have undergone chemotherapy or radiation constitute the highest risk group.
      There are only a few articles about hemorrhagic cystitis in pregnancy, that is
      the reason why the therapy for this disorder is not uniform. Hemorrhagic cystitis
      in pregnant women frequently is associated with preterm labor. We describe one
      patient with a clinical status of hematuria, dysuria, frequency, urgency and
      premature labor. The cystoscopic study showed data that suggest hemorrhagic
      cystitis. The various treatment used in this disorder are reviewed here.

PMID- 9019438
TI  - [Methods of sex selection. A new method for preventing genetic diseases].
AB  - Determining sex of offspring has been a subject of intense interest for the
      public and professional community. Although methods of selecting sex before
      concepts are not entirely reliable, couples could satisfy their wishes for the
      size and composition of their family and the children might benefit by being
      wanted. On the other hand, the ability to selectively separate X from Y
      chromosome-bearing spermatozoa and use the X spermatozoa to preferentially
      produce female offspring; could be reduce, or may even eliminate, the probability
      of conceiving affected males of X-linked diseases.

PMID- 9019439
TI  - [Evaluation of ultrasonographic variables of the endometrium in relation with
      histopathologic findings in patients with postmenopausal uterine bleeding].
AB  - The purpose of this study was to determine the sensitivity, specificity, positive
      and negative predictive value of analyzed variables in the ultrasonographic
      endometrial study in patients with postmenopausal uterine bleeding. Nineteen
      women with postmenopausal uterine bleeding were studied, in all of them and in
      the same day a transvaginal ultrasound and endometrial biopsy were performed. It
      was observed that endometrial thickness median was 4 mm; most of the endometria
      were proliferative (n = 12), and a greater trend to obesity and upper segment fat
      distribution was found. Endometrial thickness, refringence and liquid on uterine
      cavity had a sensitivity and a negative predictive value NPV) of 100%,
      specificity and positive predictive value were lower. When endometrial thickness
      and refringence were associated also a sensitivity and NPV of a 100% was found.
      It can be concluded that transvaginal ultrasound is useful to define in which
      patient with postmenopausal uterine bleeding the endometrial biopsy is indicated.

PMID- 9019440
TI  - [Treatment of premenstrual tension syndrome (PMS) with lisuride maleate].
AB  - The etiology of PMS has not yet been defined, although there are several theories
      among which it is reported that there is an increase in prolactine levels
      involved in it. The purpose of this study was to evaluate a dopamine receptor
      agonist (lisuride maleate), in the treatment of PMS. 35 patients between 19 and
      35 years old were recruited in a prospective study design, with diagnosis of PMS
      and no other gynecological disorder ruled out clinical and ultrasonographic
      examination, women with no previous treatment and with no use of hormonal agents,
      these patients were treated for three months with lisuride maleate, 0.3 mg-day in
      a three dosage scheme per day, the following symptoms were evaluated: headaches,
      mastalgia, bloating, edema of lower extremities and myalgia in legs, as well as
      hormonal parameters before and after treatment with estrogens, progesterone,
      prolactine, luteinizing hormone (LH), follicle stimulating hormone (FSH) and
      testosterone, which were prescribed in the luteal phase (day 21). Results
      obtained were: reduction of all symptoms scores versus pretreatment: Headache
      from 85.7 to 20%, mastalgia from 91.4 to 25%, bloating from 74.2 to 40%, edema in
      lower extremities from 85.7 to 30%, myalgia in legs, from 61 to 34%. The hormonal
      profile only showed changes in FSH, since the basal pretreatment level was found
      in 18.6 and the post-treatment value was 13.86, progesterone from 2.7 to 4.6 and
      prolactine from 7.74 to 6.82. We conclude the lisuride maleate is a good option
      to the PMS treatment, since a significative reduction of symptoms are induced and
      it is well tolerated.

PMID- 9019441
TI  - Proceedings of the 1st International summit meeting on Immunological Correlates
      of Protection from HIV Infection and Disease. Mont Pelerin, Switzerland, 27-30
      May 1995.

PMID- 9019442
TI  - Severe organophosphate poisoning in a neonate.

PMID- 9019443
TI  - Myelofibrosis secondary to SLE and its reversal on steroid therapy.

PMID- 9019444
TI  - [Acute myeloid leukemia].

PMID- 9019445
TI  - [Chronic myeloid leukemia. Current strategies in diagnosis, therapy and follow
      up].

PMID- 9019446
TI  - [Chronic lymphatic leukemia. Progress in diagnosis and therapy].

PMID- 9019447
TI  - [Value of hematopoietic stem cell transplantation in treatment of leukemia].

PMID- 9019448
TI  - [Experimental approaches].

PMID- 9019449
TI  - [Critical peripheral ischemia in infection].

PMID- 9019450
TI  - [A rare cause for gastrointestinal hemorrhage. Diagnosis and therapy].

PMID- 9019451
TI  - [A therapeutic alternative to the economical vitamin D is the active metabolite
      calcitriol].

PMID- 9019453
TI  - [Naltrexone--prevention of recurrence in narcotic dependence and in alcoholism].

PMID- 9019454
TI  - [Cytokines].

PMID- 9019452
TI  - [Is there an indication for intravenous iron replacement in, for example, by
      autologous blood donation-induced iron deficiency and is there a theoretically
      possible indication for intravenous administration for the not approved Ferrum
      Hausmann preparation?].

PMID- 9019455
TI  - [Progress in understanding the development of leukemia. Consequences for the
      clinic].

PMID- 9019456
TI  - [Acute leukemia in childhood. Classification--diagnosis--therapy--prognosis].

PMID- 9019457
TI  - [Acute lymphatic leukemia of the adult. Diagnosis, risk groups and therapy].

PMID- 9019458
TI  - Topical corticosteroids reverse the antiviral effect of topical cidofovir in the
      Ad5-inoculated New Zealand rabbit ocular model.
AB  - PURPOSE: To determine how the addition of topical corticosteroids would affect
      the anti-adenoviral inhibitory effect of topical cidofovir (S-HPMPC) in the Ad5
      New Zealand (Ad5/NZ) rabbit ocular model. METHODS: In a series of experiments
      (two-eye design), Ad5-inoculated/NZ rabbits (10(6) pfu/eye) were treated with 1
      of 3 treatment regimens. Group 1 was administered 1% cidofovir (CDV) twice a day
      for 3 days plus comfort tears four times a day for 14 days. Group 2 was
      administered 1% CDV twice a day for 3 days plus 1% Pred Forte four times a day
      for 14 days. Group 3 was administered vehicle twice a day for 3 days plus comfort
      tears four times a day for 14 days and served as the control. All eyes were
      evaluated for 21 days for serial eye titers, Ad5 positive eyes, and duration of
      Ad5 shedding. RESULTS: Compared to control eyes in the Ad5/NZ rabbit ocular
      model, CDV alone demonstrated a significant antiviral inhibitory effect: reduced
      mean Ad5 eye titer during the early phase of infection (days 3 to 7), fewer Ad5
      positive eyes during the early and late (days 9 to 21) phases of infection, and
      shortened duration of shedding. However, concomitant treatment with both Pred
      Forte and CDV significantly reversed the antiviral inhibitory activity of CDV:
      increased mean Ad5 eye titer, increased Ad5-positive eyes (early and late phases)
      and prolonged duration of shedding. CONCLUSIONS: These experimental data further
      support the clinical development of cidofovoir as a topical antiviral agent, but
      they do not support a treatment regimen that includes a combination of topical
      corticosteroids and topical cidofovir as a desirable strategy for the treatment
      of symptomatic adenoviral ocular infection.

PMID- 9019459
TI  - Kinin '95. Proceedings of the 14th International Symposium on Bradykinin and
      Related Kinins. Denver, Colorado, 10-15 September 1995.

PMID- 9019460
TI  - [Lasers in ear surgery].

PMID- 9019461
TI  - [Exposure to anesthetic gases at the work site].

PMID- 9019462
TI  - [The Wurzburg free-field audiometry--categorial loudness scaling].

PMID- 9019463
TI  - [Early auditory evoked potential. A diagnostic parameter in uremic
      encephalopathy].
AB  - The brainstem auditory evoked responses (BAERs) of 87 patients with chronic renal
      failure (average age 51 years) were examined according to serum creatinine
      levels, the nature of the chronic renal disease present and the effect of
      dialysis. Changes recorded were followed over a period of 3 years. Altogether
      BAERs of 272 ears were evaluated. Results demonstrated changes in wave morphology
      and abnormal prolongations of all wave latencies and interpeak intervals. Wave V
      latencies and the interpeak interval for waves I-V showed a correlation to serum
      creatinine levels. The direct positive effect of dialysis was reflected in
      shortening of all wave latencies. The nature of the chronic renal disease and the
      existence of coexistence diseases were not important for changes in central BAER
      responses. The recording of the intra-individual course of a BAER permitted
      documentation of worsened cerebral function even in patients with constant uremic
      conditions.

PMID- 9019464
TI  - [Exposure of operating room personnel to anesthetic gases during ENT
      interventions].
AB  - During ENT surgical procedures under general anesthesia contamination of the
      operating room air through waste anesthetic gases seems unavoidable. A resulting
      chronic low-level exposure to anesthetic gases in subanesthetic concentrations
      (m1/m3 = ppm) may cause various negative health effects. The aim of this study
      was to quantify possible side effects on operating room personnel. By using a
      highly sensitive, direct reading instrument for determining contamination leakage
      from a patient's mouth and resulting concentrations in the breathing zone of the
      surgeon and anesthetist, levels of isoflurane and nitrous oxide were measured at
      2-min intervals during 20 ENT surgical procedures performed under usual workplace
      conditions. Despite high concentrations of anesthetic at the mouth of each
      patient, personnel-related mean values remained under recommended threshold
      values (TLV) of 10 ppm isoflurane. A TLV of 100 ppm nitrous oxide was exceeded in
      20% of the operations. Furthermore, a safe TLV for pregnant staff was 25 ppm
      nitrous oxide. This value was exceeded during nearly all operations (93%) for the
      group "surgeon". High leakages at the patient's mouth led to an undesirably high
      contamination of operating room personnel by nitrous oxide. Although threshold
      values were mostly not exceeded in available working conditions (i.e., adequate
      air conditioning and intubation cuff pressure control), present health and safety
      regulations concerning pregnant women showed that the values of nitrous oxide
      were still too high to allow such women to work safely in operating rooms during
      surgery. However, exposure to isoflurane was too slight to classify.

PMID- 9019465
TI  - [Peripheral branches of the facial nerve in the cheek and chin area. Anatomy and
      clinical consequences].
AB  - The available descriptions of the innervation of the depressor anguli oris muscle
      and the peripheral distribution of the terminal branches of the marginal
      mandibular branch and buccal branches of the facial nerve are conflicting. Based
      upon dissections of 25 head halves we investigated the courses of the terminal
      branches of the marginal mandibular and buccal nerves. The marginal mandibular
      and buccal branches were found to form in the area of the mental foramen the
      mental and buccal plexus innervating the mimetic muscles by terminal nerve
      branches in the cheek area. The buccal plexus supplied the muscles of upper lip,
      cheek and nose. Furthermore, the depressor anguli oris muscle was also supplied
      by the buccal plexus. We also observed connections between marginal mandibular
      branch and mental nerve and between buccal branches of the facial nerve and
      buccal nerve of the trigeminal nerve. In case of injury to the marginal
      mandibular branch the depressor anguli oris muscle is not affected. Injury to the
      nerve branches of the depressor anguli oris muscle can be caused by operations or
      lesions in the area of the posterior border of this muscle.

PMID- 9019466
TI  - [Direct loudness scaling in diagnosis of tinnitus. A contribution to loudness
      perception in tinnitus].
AB  - We used free-field audiometry to investigate the loudness perception of
      unilateral high-frequency tinnitus in 16 "normal-hearing" ears by comparing the
      results with loudness scaling in 20 normally hearing ears without any tinnitus.
      Narrow-band noise signals at four different frequencies from 500 to 4000 Hz were
      employed. The parameters used included the slope m of the loudness function and
      the level Lm (corresponding to the loudness perception of "medium loud") as well
      as the suitability of fit (delta FIT). The results showed that in subjects with
      tinnitus the slope of the mean loudness level tended to decrease at 4000 Hz. The
      dynamic range of ears affected by tinnitus was restricted for stimulation with
      noise signals at 1000, 2000 and 4000 Hz. The parameters of delta FIT fitted to
      the loudness functions were increased in the whole frequency range of 500-4000
      Hz, indicating that loudness scaling was not as reliable for normal hearing ears
      when influenced by tinnitus. Tinnitus masking was based on the finding that
      external sound could change tinnitus loudness. Our results showed that the
      loudness perception of external sound was influenced by tinnitus. This change in
      loudness perception seemed to be not restricted to the frequency range of the
      tinnitus.

PMID- 9019467
TI  - [Computer-assisted 3D phonetography].
AB  - Profiles of fundamental frequency sound pressure levels and voice duration are
      measured separately in clinical practice. It was the aim of the present study to
      combine the two examinations, in order to estimate the relationship between
      pitch, sound pressure level and voice duration and to develop a new computer
      assisted graph. A three-dimensional (3D) wireframe phonogram was constructed
      based on SPL profiles to obtain a general view of the parameters recorded. We
      have termed this "phonetography". Variable further projections were selected for
      the analysis of different aspects of parametric relationships. The results in 21
      healthy volunteers and 4 patients with hyperfunctional dysphonias demonstrated
      that there were three typical figures of the 3D phonograms produced, depending on
      the relationship between voice duration when soft ("piano") compared to loud
      ("forte"). In one-third of the healthy volunteers, the values of the piano voice
      duration were greater than those of forte for almost all pitches examined. In two
      thirds of the healthy subjects the values of forte voice duration were partly
      greater, as were those of piano voice duration. All of the patients showed voice
      duration values greater for forte than for piano. The results of the study
      demonstrate that the 3D phonogram is a useful tool for obtaining new insights
      into various relationships of voice parameters.

PMID- 9019468
TI  - [Facial injury caused by an umbrella spoke].
AB  - We report an unusual injury of the face caused by the spoke of an automatic
      telescoping umbrella that come loose when the umbrella was opened. Due to the
      shot-like force of the spoke, the left nostril, septum and right wall of the
      nasal cavity were pierced. The part with the joint penetrated into the maxillary
      antrum. In order to remove the spoke, wire scissors had to be used to cuff off
      the spoke's joint inside the surgically opened maxillary sinus.

PMID- 9019469
TI  - [Accidental dirt tattooing. Removal with Q-switched ruby laser].
AB  - The Q-switched ruby laser (wave length 694 nm; pulse durations 25 ns or 40 ns)
      cause selective damage to natural and artificial skin pigments. Treatable lesions
      include benign pigmented growths (benign, lentigo, ephelides, cafeau-lait spots
      and Becker's nevi), as well as amateur and professional tattoos. The Q-switched
      ruby laser is also very effective in the treatment of traumatic tattoos. We
      report our experiences with two patients whose traumatic tattoos resolved
      completely without any scarring after ruby laser therapy. Our findings show that
      Q-switched ruby laser treatment may represent the therapy of choice for these
      tattoos.

PMID- 9019470
TI  - [Testing smell and taste].

PMID- 9019471
TI  - [Using cartilage in middle ear surgery].

PMID- 9019472
TI  - Sexual dysfunction and antidepressants.

PMID- 9019473
TI  - Ongoing needs in depression. Symposium highlights from the World Congress of
      Psychiatry held in August 1996 in Madrid, Spain.

PMID- 9019474
TI  - Local interactions in protein folding: lessons from the alpha-helix.

PMID- 9019475
TI  - Publication, ethics, and scientific integrity.

PMID- 9019476
TI  - A highly porous 3-dimensional polyphosphazene polymer matrix for skeletal tissue
      regeneration.
AB  - Current methods for the replacement of skeletal tissue in general involve the use
      of autografts or allografts. There are considerable drawbacks in the use of
      either of these tissues. In an effort to provide an alternative to traditional
      graft materials, a degradable 3-dimensional (3-D) osteoblast cell-polymer matrix
      was designed as a construct for skeletal tissue regeneration. A degradable amino
      acid containing polymer, poly[(methylphenoxy)(ethyl glycinato) phosphazene], was
      synthesized and a 3-D matrix system was prepared using a salt leaching technique.
      This 3-D polyphosphazene polymer matrix system, 3-D-PHOS, was then seeded with
      osteoblast cells for the creation of a cell-polymer matrix material. The 3-D-PHOS
      matrix possessed an average pore diameter of 165 microns. Environmental scanning
      electron microscopy revealed a reconnecting porous network throughout the polymer
      with an even distribution of pores over the surface of the matrix. Osteoblast
      cells were found attached and grew on the 3-D-PHOS at a steady rate throughout
      the 21-day period studied in vitro, in contrast to osteoblast growth kinetics on
      similar, but 2-D polyphosphazene matrices, that showed a decline in cell growth
      after 7 days. Characterization of 3-D-PHOS osteoblastpolymer matrices by light
      microscopy revealed cells growing within the pores as well as on surface of the
      polymer as early as day 1. This novel porous 3-D-PHOS matrix may be suitable for
      use as a bioerodible scaffold for regeneration of skeletal tissue.

PMID- 9019477
TI  - The burst phenomenon, an animal model simulating the long-term tissue response on
      PLLA interlocking nails.
AB  - In this in vivo study, low-molecular-weight as-polymerized PLLA powder was placed
      in the medullary cavity of a porcine femur in order to study the tissue reaction
      on predegradated PLLA. An attempt was made to simulate the long-term degradation
      of a large PLLA implant. This phase can be characterized by the release of PLLA
      particles and acid compounds from a heterogeneously degrading PLLA implant into
      the surrounding tissues. The clinical consequences and tissue response were
      studied. The clinical recovery of the experimental animals was favorable. No
      signs of clinical inflammation could be detected during the eight-week follow-up
      period. Histological analysis of the bone/PLLA interface showed signs of a mild
      inflammatory tissue response.

PMID- 9019478
TI  - Effect of titanium surface roughness on chondrocyte proliferation, matrix
      production, and differentiation depends on the state of cell maturation.
AB  - Although it is well accepted that implant success is dependent on various surface
      properties, little is known about the effect of surface roughness on cell
      metabolism or differentiation, or whether the effects vary with the maturational
      state of the cells interacting with the implant. In the current study, we
      examined the effect of titanium (Ti) surface roughness on chondrocyte
      proliferation, differentiation, and matrix synthesis using cells derived from
      known stages of endochondral development. Chondrocytes derived from the resting
      zone (RCs) and growth zone (GCs) of rat costochondral cartilage were cultured on
      Ti disks that were prepared as follows: HF-HNO3-treated and washed (PT); PT
      treated and electropolished (EP); fine sand-blasted, HCl-H2SO4-etched, and washed
      (FA); coarse sand-blasted, HCl-H2SO4-etched, and washed (CA); or Ti plasma
      sprayed (TPS). Based on surface analysis, the Ti surfaces were ranked from
      smoothest to roughest: EP, PT, FA, CA, and TPS. Cell proliferation was assessed
      by cell number and [3H]-thymidine incorporation, and RNA synthesis was assessed
      by [3H]-uridine incorporation. Differentiation was determined by alkaline
      phosphatase specific activity (AL-Pase). Matrix production was measured by [3H]
      proline incorporation into collagenase-digestible (CDP) and noncollagenase
      digestible (NCP) protein and by [35S]-sulfate incorporation into proteoglycan.
      GCs required two trypsinizations for complete removal from the culture disks; the
      number of cells released by the first trypsinization was generally decreased with
      increasing surface roughness while that released by the second trypsinization was
      increased. In RC cultures, cell number was similarly decreased on the rougher
      surfaces; only minimal numbers of RCs were released by a second trypsinization.
      [3H]-thymidine incorporation by RCs decreased with increasing surface roughness
      while that by GCs was increased. [3H]-Uridine incorporation by both GCs and RCs
      was greater on rough surfaces. Conversely, ALPase in the cell layer and isolated
      cells of both cell types was significantly decreased. GC CDP and NCP production
      was significantly decreased on rough surfaces while CDP production by RC cells
      was significantly decreased on smooth surfaces. [35S]-sulfate incorporation by
      RCs and GCs was decreased on all surfaces compared to tissue culture plastic. The
      results of this study indicate that surface roughness affects chondrocyte
      proliferation, differentiation, and matrix synthesis, and that this regulation is
      cell maturation dependent.

PMID- 9019479
TI  - Migration of metal and polyethylene particles from articular prostheses may
      generate lymphadenopathy with histiocytosis.
AB  - Wear particles released from hip or knee prostheses are known to be involved in
      the fibrohistiocytic membrane interposed between bone and implant. During
      surgical treatment for pelvic carcinoma (5 cases) and for isolated
      pseudomalignant lymphadenopathy (4 cases) lymph nodes in 9 patients who had had
      lower limb articular replacement were harvested. Light microscopy and image
      analysis of the nodes showed florid endosinusal histiocytosis, predominant in the
      cortical area. Using Oil Red O staining and polarized light, metal particles and
      polyethylene particles were detected in the large histiocytes. Scanning electron
      microscopy with electron backscattering allowed us to localize metal particles
      and perform elemental microanalysis. Iron, cobalt, chromium, nickel, zirconium,
      and barium, known to be used in prosthetic and cementing materials, were
      identified as component of these particles. Large amounts of polyethylene
      particles appeared in all cases while metal particles were found to be abundant
      in only 2 cases. Thus, migration of polyethylene debris from the prosthetic site
      seems to be the major factor in development of the histiocytes induced in
      satellite lymph nodes.

PMID- 9019480
TI  - The application of ion beam analysis to calcium phosphate-based biomaterials.
AB  - Ion beam technology may be applied in a straightforward fashion to the analysis
      and modification of biomaterials. For analytical purposes, characterization using
      megaelectron-volt He2+ ions provides a standardless, nondestructive means for
      accurately quantifying the composition of material surfaces and the thickness of
      thin films. In this study, three complementary ion backscattering techniques were
      utilized to characterize hydroxyapatite (HA) films: Rutherford backscattering
      spectrometry (RBS) can determine composition and amounts of elements heavier than
      He; forward recoil elastic spectrometry (FRES) can determine hydrogen content;
      resonance-enhanced RBS can quantify small amounts of light elements, e.g. carbon,
      by choosing a particular incident beam energy resulting in excitation of the
      light element nucleus. At this resonance energy, the scattering cross section
      greatly increases, improving elemental sensitivity. Sol-gel chemistry was used to
      synthesize HA films by spin coating and annealing in a rapid thermal processor.
      Using these techniques, the chemical composition of unfired films was
      Ca1.63O5.4H1.8C0.24P with a thickness of 3.01 x 10(18) atoms/cm2 and after firing
      at 800 degrees C as Ca1.66O4.0H0.26C0.09P with a thickness of 2.11 x 10(18)
      atoms/cm2. This compares favorably to stoichiometric HA, which has a composition
      of Ca1.67O4.33H0.33P.

PMID- 9019481
TI  - Inability of energy dispersive X-ray analysis to identify particulate
      polyethylene.
AB  - There are limitations to all techniques used to identify particulate polyethylene
      in histological specimens. The goal of our study was to determine if remnant
      metal elements used during the catalytic production of ultra high molecular
      weight polyethylene, could be used as markers for particulate polyethylene
      detection in histological specimens. It was hypothesized that these catalyst
      elements could be detected in polyethylene using energy dispersive X-ray
      elemental analysis. Six samples from five different companies were evaluated.
      These included virgin polymer powder, polyethylene bar stock, and artificial
      joint components. Five specimens from each of the six samples were analyzed with
      energy dispersive X-ray elemental analysis. After elemental analysis was
      completed, only 2 of 30 specimens were positive for the catalyst elements. In the
      remaining 28 specimens, catalyst elements were not detected. Our investigation
      demonstrates that energy dispersive X-ray elemental analysis is not currently a
      feasible method of particulate polyethylene detection. Additional techniques will
      need to be developed to accurately identify particulate polyethylene in
      histological specimens.

PMID- 9019482
TI  - Design-related fretting wear in modular neck hip prosthesis.
AB  - An accelerated cyclic loading corrosion test was used to determine the corrosion
      behavior of a commercial (GSP) and a prototype titanium hip prosthesis each with
      a modular neck. Four GSP and four prototype stems were subjected to a 2-Hz cyclic
      load ranging between 200 and 2,100 N for 1,000,000 cycles. Three stems were
      tested in an environment of FeCl3 solution, three stems were tested in Ringer's
      solution, and two stems were tested in air. After cyclic loading, the specimens
      were carefully examined with optical and scanning electron microscopy (SEM). None
      of them showed macroscopic or microscopic signs of corrosion, regardless of the
      environment to which the specimens were subjected. However, macroscopic evidence
      of mechanical fretting was present at the neck-stem modular junction, primarily
      concentrated at the medial contact point between stem and neck, especially for
      the prototype stems. SEM analysis confirmed these observations. The appreciable
      differences observed between the two designs suggest that the problem can be
      minimized or eliminated with an accurately designed taper fitting.

PMID- 9019483
TI  - Characteristics of poly(L-)lactic acid suture applied to fascial closure in rats.
AB  - A new poly(L-)lactic acid (PLLA) thread was tested by applying it in fascial
      closures of male Wistar rats. The tissue reactions around the thread and in the
      fascial union, and the changes on the surface and the mechanical properties of
      the thread were evaluated at 1, 3, 6, 12, 28, and 52 weeks following surgery.
      Histologically, the extension of the general inflammatory reaction and the number
      of the different cell types did not markedly change during the 52-week follow-up
      period. The surface of the thread was intact up to 28 weeks when examined with
      the scanning electron microscope. At 52 weeks no thread was found. The breaking
      force and the stretching of the incubated PLLA thread was reduced about 20%
      during the first 2 weeks and it remained constant up to 6 weeks. The in vivo
      testing of the fascial strips closed with the PLLA thread retained their
      resistance against the breaking force, nearly comparable to that of the intact
      control fascial strips. It can be concluded that the PLLA thread is a suitable
      suture for wounds that require healing time of up to 28 weeks and thus need good
      support from the suture.

PMID- 9019484
TI  - Resorption of, and bone formation from, new beta-tricalcium phosphate-monocalcium
      phosphate cements: an in vivo study.
AB  - Hard cylinders (4.7 x 10 mm) of two kinds of beta-tricalcium phosphate
      monocalcium phosphate monohydrate-calcium sulfate hemihydrate (beta-TCP-MCPM-CSH)
      cements with and without beta-TCP granules (500-1000 microns) were implanted into
      holes drilled in rabbit femoral condyles for up to 16 weeks. Empty cavities were
      used as control. Cement resorption and new bone formation in the cylinders were
      evaluated with contact microradiography and quantified through an automatic image
      analysis system. At 4 weeks, both kinds of cement cylinders were surrounded by
      new bone. At 8 weeks, except for beta-TCP granules, both cement cylinders were
      almost completely resorbed and replaced by bone tissue. At 16 weeks the bone in
      the cavities of both cements recovered a trabecular pattern, but only the bone
      trabeculae in the initial cavity of the cement with beta-TCP granules became
      thick and mature. However, the cavities of the empty control were still empty and
      large. These results show that the beta-TCP-MCPM-CSH cements stimulate bone
      formation and are rapidly replaced by bone tissue. When added with nonresorbable
      beta-TCP granules, this cement maintains bone formation for a longer time.

PMID- 9019485
TI  - Hydrolytic degradation of films prepared from blends of high and low molecular
      weight poly(DL-lactic acid)s.
AB  - Biodegradable films were prepared by casting acetone solutions of mixtures of a
      high molecular weight poly(DL-lactic acid) (HMW-PLA50) with 0, 10, and 30% w/w
      poly(DL-lactic acid) oligomers (LMW-PLA50), before drying. From size exclusion
      chromatography (SEC) it was shown that degradation occurred during film
      processing, in agreement with the acid-catalyzed degradation of polyesters. The
      higher the content of LMW-PLA50, the larger the decrease of the molar masses. The
      three selected film formulations were then allowed to age in isoosmolar 0.13M, pH
      7.4 sodium phosphate buffer at 37 degrees C. The hydrolytic degradation was
      monitored by using various techniques, namely weighing to quantify water
      absorption and weight loss, SEC to evaluate molar mass changes, head space gas
      chromatography to assess the desorption of residual acetone, and enzymatic assay
      of the L-lactic acid released in the aging media. The presence of LMW-PLA50
      clearly accelerated film degradation. Moreover, it was shown that the mechanism
      of degradation greatly depended on the content in the oligomers.

PMID- 9019486
TI  - Human endothelial cell growth and coagulant function varies with respect to
      interfacial properties of polymeric substrates.
AB  - The in vitro coagulant function of human aortic endothelial cells (HAECs) was
      investigated when grown on a series of polymer surfaces that ranged from
      hydrophobic to hydrophilic. The polymer interface materials were prepared by
      radiofrequency plasma polymerization from hexamethyl-disilazane, gamma
      butyrolactone, and N-vinyl-2-pyrrolidone and deposited onto tissue culture
      Permanox. The three plasma polymers were noncytotoxic. When precoated with
      fibronectin (FN), HAECs on all four polymer surfaces were similar with respect to
      cell proliferation and coagulant function. Without FN precoating, cell
      proliferation and spreading increased with increasing surface hydrophilicity.
      Normalized production of tissue-type plasminogen activator increased with
      increasing hydrophilicity of the polymers during early incubation times, as did
      tissue plasminogen activator/plasminogen activator inhibitor-1 ratios. In
      comparison, normalized von Willebrand factor release decreased on the more
      hydrophilic surfaces. Thus, both endothelial cell growth and some
      coagulant/fibrinolytic functions are improved with increasing substrate
      hydrophilicity.

PMID- 9019487
TI  - Performance of small diameter synthetic vascular prostheses with confluent
      autologous endothelial cell linings.
AB  - Autologous grafts are superior to their synthetic counter-parts for grafting
      arteries smaller than 6-mm diameter both in terms of acute thrombogenicity and
      chronic intimal hyperplasia. Endothelial cell (EC) coating of the blood
      contacting surface may reduce thrombogenicity of synthetic small diameter
      vascular prostheses. In this study, the survival of EC monolayers on synthetic 4
      mm diameter arterial prostheses over short-term implantations (< or = 6 weeks)
      was examined. Graft types examined were expanded polytetra-fluoroethylene (ePTFE)
      and microporous polyurethane (PU). Lumenal coverage with ECs was achieved by
      culturing ovine ECs on prostheses treated by either physical adsorption or
      covalent binding of ovine fibronectin (Fn). An ovine carotid interposition model
      was used to examine the performance of EC coated ePTFE and microporous PU over
      implantation periods of 1, 3, and 6 weeks. Outcomes assessed at the end of each
      experiment were graft patency, area covered by ECs, and thrombus free surface
      area (TFSA). Fn concentration, cell density at the time of coating and
      prostacyclin production in vitro were similar for both graft types. Occlusion
      occurred more frequently in unseeded grafts compared with EC coated grafts over 3
      and 6 week implantation periods; however, the difference was not significant (p =
      0.099). In prostheses precoated with ECs, approximately 40-60% of the surface
      area remained covered with endothelial-like cells following the first
      postoperative week. Recovery of EC layers occurred rapidly thereafter with 80-90%
      coverage at 3 weeks. TFSA remained low in comparison to EC cover in these
      prostheses until between 3 and 6 weeks postoperatively, suggesting a lag phase in
      recovery of EC function of seeded cells. In contrast, EC cover of unseeded
      prostheses only achieved 10-30% at 3 weeks, primarily by pannus EC ingrowth from
      the adjacent artery. TFSA of unseeded grafts increased in direct proportion to EC
      cover over time suggesting that there was no lag phase in function of these
      ingrowing cells.

PMID- 9019488
TI  - Characterization of silane-treated hydroxyapatite powders for use as filler in
      biodegradable composites.
AB  - Hydroxyapatite (HA) powder was treated with different silane adhesion promoters,
      to optimize its performance as a filler in polymer composites. The silane
      coupling agents investigated possessed vinyl, methacryloxy, primary amine,
      secondary amine, and diamine functionality. The different coatings were evaluated
      with respect to their influence on ionic exchange. X-ray photoelectron
      spectroscopy revealed the presence of a few monolayers thin silane films on HA
      powder. Silane coupling agents were able to bond chemically on the HA surface
      because a thin coating remained after washing of the powder with water. The water
      stability of this bond was evaluated by successive extractions and was judged
      limited, especially in the case of the hydrophilic aminosilanes. Zeta-potential
      measurements indicated the "transparency" of the coatings for ionic transport,
      that was corroborated by two in vitro dissolution studies, in Gomori's Tris
      maleate buffer, and in simulated body fluid. However, aminosilane coatings could
      delay the release of calcium and phosphate ions during the first 2 days of
      immersion of treated HA powder in Gomori's buffer.

PMID- 9019489
TI  - Effect of high external pressures on the vibrational spectra of biomedical
      materials: calcium hydroxyapatite and calcium fluoroapatite.
AB  - Infrared and Raman spectra of the principal mineral component of human hard
      tissue, calcium hydroxyapatite, Ca10(PO4)6(OH)2, or HAP, and the analogous
      calcium fluoroapatite, Ca10(PO4)6F2, or FAP, have been recorded, using a diamond
      anvil cell, at pressures ranging from ambient to 30 kbar. For FAP, the absence of
      any discontinuities in the slopes of the nu (cm-1) versus P (kbar) plots for the
      observed bands indicates that no pressure-induced structural transition occurs in
      this material throughout the pressure range investigated. For the internal
      vibrational modes of HAP, however, there are distinct breaks at approximately 20
      kbar in the nu versus P plots, suggesting the occurrence of a structural change
      at this pressure. The OH stretching mode of HAP shifts to higher wave numbers
      with increasing pressure while the associated OH librational mode shifts in the
      opposite direction. The pressure-induced structural transition in HAP is
      reversible and occurs at approximately 22 kbar upon decompression. Further
      evidence for a structural change taking place at approximately 20 kbar was
      provided by a parallel pressure-tuning Raman study. Hydrogen bonding does not
      occur, or is very weak, in HAP.

PMID- 9019490
TI  - Contribution of vascular catheter material to the pathogenesis of infection:
      depletion of complement by silicone elastomer in vitro.
AB  - We previously have shown that vascular catheters made of silicone elastomer carry
      a greater risk of subcutaneous infection with Staphylococcus aureus than do
      polyurethane (PU), polyvinylchloride (PVC), or Teflon catheters. We further have
      shown that there is greater inflammation surrounding silicone catheters than
      there is surrounding catheters made of the other materials, suggesting that
      silicone produces a greater chemotactic gradient than do the other materials.
      This study used a functional complement opsonization assay and radioimmunoassays
      to compare the relative abilities of silicone, polyurethane, and
      polyvinylchloride to activate complement. Serum incubated in silicone catheters
      for 24 h had less than 30% of the opsonizing ability of fresh serum while > or =
      78% of the opsonizing ability remained with serum incubated in PU or PVC
      catheters. Measurement of C3a des Arg, C4a des Arg, C5a des Arg, and SC5b-9
      demonstrated that the loss of opsonizing ability was due to 10-fold greater
      alternate pathway complement activation by silicone than by PU or PVC. This
      finding suggests that excessive complement activation by silicone may explain the
      greater inflammation seen around silicone catheters in vivo and also might play a
      role in silicone's creating a greater risk of infection.

PMID- 9019491
TI  - Torque and histomorphometric evaluation of c.p. titanium screws blasted with 25-
      and 75-microns-sized particles of Al2O3.
AB  - A comparison was made between screw-shaped c.p. titanium implants blasted with
      either 25- or 75-microns particles of Al2O3. The implant surfaces were
      investigated with respect to topography and composition before implantation in
      rabbit bone. Grit blasting with 25- or 75-microns particles produced two
      different surface roughnesses, but no significant difference in the surface
      composition for the two surfaces. After 12 weeks insertion time in the rabbit
      tibia and femur, a higher removal torque and more bone-to-metal contact was found
      for the implants blasted with 75-microns particles compared with the 25-microns
      blasted ones.

PMID- 9019493
TI  - Special issue: The Symposium of World Dermatology Update held in conjunction with
      the 59th annual meeting of Tokyo Dermatological Society.

PMID- 9019492
TI  - Bone-bonding behavior of plasma-sprayed coatings of BioglassR, AW-glass ceramic,
      and tricalcium phosphate on titanium alloy.
AB  - The bone-bonding behavior of three kinds of bioactive ceramics coated on titanium
      alloy by the plasma-spray technique was investigated. Titanium alloy (Ti-6A1-4V)
      coated with BioglassR (45S5), apatite-wollastonite containing glass ceramic (AW),
      or beta-tricalcium phosphate (TCP) was prepared, and rectangular specimens were
      implanted into the tibial bones of mature male rabbits, which were sacrificed 8
      or 24 weeks after implantation. The tibiae containing the implants were dissected
      out and subjected to detachment tests to measure the failure load. The bone
      implant interface was investigated by Giemsa surface staining, contact
      microradiography, and scanning electron microscopy-electron probe microanalysis
      (SEM-EPMA). Eight weeks after implantation, the failure loads for implants coated
      with BioglassR, AW, and TCP were 1.04 +/- 0.94, 2.03 +/- 1.17, and 3.91 +/- 1.51
      kg, respectively, and 24 weeks after implantation, the respective failure loads
      were 2.72 +/- 1.33, 2.39 +/- 1.30, and 4.23 +/- 1.34 kg. Failure loads of AW- and
      TCP-coated implants did not increase significantly with time. After the
      detachment test, breakage of the coating layer was observed. Bioactive ceramics
      can act as stimulants that induce bonding between bone and metal implants.
      However, failure load of metal implants coated with the bioactive ceramics was
      lower than that of bulk AW or TCP. It appears impossible to obtain a higher
      failure load using a bioactive-ceramic coating on titanium alloy. Histologically,
      the coating layer was found to become detached from the metal implant and the
      bone tissue bonded to the coating layer. SEM-EPMA observation revealed breakage
      of the coating layer, although bonding between bone and the coating layer was
      evident. A Ca-P-rich layer was observed at the interface between bone and the AW
      coating, and a Ca-P-rich and a Si-rich layer were observed at the interface
      between bone and the BioglassR coating. For clinical application, it would seem
      better to use coated metal implants for short-term implantation. However, there
      is a possibility of breakage of the coating layer because of both dissolution of
      the bioactive ceramic and mechanical weakness at the interface between the
      coating layer and the metal implant.

PMID- 9019494
TI  - The ADA Washington office.

PMID- 9019495
TI  - The effect of post-cure heat treatment systems on composite resin restorations.

PMID- 9019496
TI  - Solving the problem of the tissue-impinging lingual bar.

PMID- 9019497
TI  - [Physiopathology of intractable diseases and prospects of the new therapy].

PMID- 9019498
TI  - [Coping with pathological changes in nerves and blood vessels in collagen disease
      -CNS lupus].

PMID- 9019499
TI  - [Coping with pathological changes in nerves and blood vessels in collagen disease
      -vasculitis syndrome and polyneuritis].

PMID- 9019500
TI  - [Coping with pathological changes in nerves and blood vessels in collagen disease
      -antiphospholipid syndrome and thrombosis].

PMID- 9019501
TI  - [Coping with pathological changes in heart of patients with collagen disease].

PMID- 9019503
TI  - [Recent clinical circumstance causing by antibiotics-resistant bacterial
      strains].

PMID- 9019502
TI  - [Coping with pathological changes in heart and lung in collagen diseases-
      pulmonary hypertension].

PMID- 9019504
TI  - [Coping with pathological changes in heart and lung in collagen diseases-
      pulmonary alveolar hemorrhage].

PMID- 9019506
TI  - [Coping with pathological changes in digestive system in patients with collagen
      disease].

PMID- 9019505
TI  - [Coping with pathological changes in heart and lung in collagen diseases-
      dermatomyositis and interstitial pneumonia].

PMID- 9019507
TI  - [Coping with pathological changes in digestive system and kidney in collagen
      disease --rapidly progressive glomerulonephritis].

PMID- 9019508
TI  - [Coping with pathological changes in digestive system and kidney in collagen
      diseases--special reference to Sjogren's syndrome and interstitial nephritis].

PMID- 9019509
TI  - [Coping with intractable symptoms in collagen diseases--Behcet's disease].

PMID- 9019510
TI  - [Coping with intractable skin ulcers in patients with collagen diseases].

PMID- 9019511
TI  - [Coping with intractable femur head necrosis in patients with collagen diseases].

PMID- 9019512
TI  - [Coping with opportunistic mycoses in patients with collagen diseases].

PMID- 9019513
TI  - [Steroid therapy and immunotherapy of patients with collagen diseases].

PMID- 9019514
TI  - [Limit on therapy of patients with collagen disease (discussion)].

PMID- 9019515
TI  - [Case of pheochromocytoma with crisis of diabetic ketoacidosis].

PMID- 9019516
TI  - [Case of G-CSF producing gallbladder neoplasm].

PMID- 9019517
TI  - [Case of direct Coombs-test-positive hemolytic anemia with bleeding tendency due
      to prominent low activity of factor V].

PMID- 9019518
TI  - [Case of bilateral temporal skin ulcer with temporal arteritis].

PMID- 9019519
TI  - [Case of non-trauma forearm compartment syndrome with prominent
      hypermyoglobinemia].

PMID- 9019520
TI  - [Cell differentiation process of extra-thymus gland T lymphocytes].

PMID- 9019521
TI  - Proceedings of the 6th International Symposium on Motor Neuron Disease and
      Amyotrophic Lateral Sclerosis. Dublin, Ireland, 30 October-1 November 1995.

PMID- 9019522
TI  - Colleagues in Caring.

PMID- 9019523
TI  - The case against mandibular condylotomy in the treatment of the painful, deranged
      temporomandibular joint.

PMID- 9019524
TI  - [Diagnostic imaging and functional tests--allergic rhinitis].

PMID- 9019525
TI  - [Highlights from 43 years of chemistry of naturally occurring nitrogen-containing
      heterocycles. (1). Syntheses and structure determinations of
      benzo[a]quinolizidine-type and indolo[2,3-a]quinolizidine-type alkaloids isolated
      from several plants].
AB  - Nineteen benzo[a]quinolizidine alkaloids (1-19) isolated so far from Alangium
      plants can be classified into four types (I-IV) according to their chemical
      structures. Studies on racemic and chiral syntheses of these I-IV-type alkaloids
      are reviewed with particular emphasis on the strategies and tactics for the
      syntheses employed by the author. It has been found that racemic syntheses of all
      of these types of alkaloids are possible through the "lactim ether route" or the
      "3-acetylpyridine route"; and chiral syntheses, through the "cincholoipon
      incorporating route" or the "chiral lactim ether route". As a result of such
      total syntheses, the structures and absolute configurations of four II-type, two
      III-type, and two IV-type Alangium alkaloids have been established. Extensions of
      the "chiral lactim ether route" to the syntheses of the Ochrosia alkaloid (-)
      ochropposinine [(-)-93g], the Neisosperma alkaloid (-)-ochromianine [(-)-97], and
      the Ophiorrhiza alkaloid (-)-ophiorrhizine [(-)-98] have unequivocally
      established the absolute stereochemistries of these three indolo[2,3-a]
      quinolizidine alkaloids.

PMID- 9019526
TI  - [Highlights from 43 years of chemistry of naturally occurring nitrogen-containing
      heterocycles. (2). Syntheses and reactions of purines and of their nucleosides].
AB  - The studies on the syntheses and reactions of purines and their nucleosides,
      carried out by the present author's group for these 34 years, are reviewed with
      particular emphasis on the employed synthetic strategies and tactics. Among the
      studies included in this review are as follows: ring-opening and recyclization of
      the adenine ring utilizing an N(1)-alkoxy group; kinetic studies of the Dimroth
      rearrangement and related reactions in the adenine series; syntheses and
      reactions of new Nx,Ny-disubstituted adenines and of new Nx-substituted
      adenosines; syntheses, structure determinations, and structure-activity
      relationships of new natural cytokinins; syntheses and reactions of new marine 8
      oxopurines; syntheses, reactions, and biological activities of the N(7)-oxides of
      guanine, hypoxanthine, adenine, 6-mercaptopurine, and 6-methylthiopurine.

PMID- 9019527
TI  - [Induction of biological activities by chemically modified subfragments from
      human serum IgG and their application to development of medicine].
AB  - Immunoglobulin G (IgG) is an important protein in humoral immunity. After IgG
      binds to the specific foreign antigen, IgG-antigen complexes are eliminated
      either by making it easier for a phagocytic cell to ingest them or by activating
      a complement system. We found that the carboxyamidemethylated subfragments
      obtained from human serum IgG by reduction and alkylation of its interchain
      disulfide bonds, have anti-ulcerogenic, anti-inflammatory and anti-allergic
      activities, while no activity was recognized in the original IgG. On the other
      hand, some saturated and unsaturated fatty acids generally existing in
      microorganisms were found to have anti-inflammatory and anti-ulcerogenic
      activities. As the application of these researches, we synthesized hybrid
      compounds from sulfur-containing amines and fatty acids to make a lead compound
      for developing a new medicine. In this review, the experimental process will be
      discussed.

PMID- 9019528
TI  - [Effect of tea-leaf saponin on blood pressure of spontaneously hypertensive
      rats].
AB  - The antihypertensive effect of tea-leaf saponin (the saponin mixture isolated
      from leaves of Camellia sinensis var. sinensis) was examined in spontaneously
      hypertensive rats (SHR). Tea-leaf saponin reduced a time-dependent increase in
      blood pressure dose-dependently when it was administered orally to young SHR (7
      weeks old) for 5 d. Oral administration of tea-leaf saponin to elder SHR (15
      weeks old) for 5 d decreased the mean blood pressure by 29.2 mmHg at the dose of
      100mg/kg compared to the control group. Single administration of tea-leaf saponin
      at 50mg/kg, p.o. showed a long-lasting hypotensive effect and this effect was as
      potent as that of enalapril maleate at the dose of 3 mg/kg, p.o. Tea-leaf saponin
      inhibited angiotensin I-induced contraction of the isolated guinea pig ileum in a
      dose dependent manner but little depressed angiotensin II-induced contraction. On
      the other hand, in in vitro experiment using a synthetic peptide as a substrate,
      tea-leaf saponin showed almost no inhibitory activity against the angiotensin I
      converting enzyme (ACE) (IC50 > 10 mg/ml).

PMID- 9019529
TI  - [Studies on the synthesis of cholecystokinin A receptor antagonists. II.
      Synthesis and cholecystokinin A receptor inhibitory activities of sulfur
      containing amide-carboxylic acid derivatives].
AB  - A number of sulfur-containing amide-carboxylic acid derivatives were synthesized
      and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to
      study structure-activity relationships. Significant CCK-A receptor inhibitory
      activities were found in only two series, that is, sulfoxide-carboxylic acid
      derivatives (9) and sulfone-carboxylic acid derivatives (10). As the most
      preferred compound, 5-(3,4-dichlorophenylsulfonyl)-4-(N,N-dipentylcarbamoyl)pent
      anoic acid (10n) was selected.

PMID- 9019530
TI  - [Colouration of toki-shakuyaku-san extract granules and the production of high
      molecular compounds under heat-stress storages].
AB  - We previously suggested that the colouration (browning) of Toki-shakuyaku-san
      extract granules (TJ-23) was related to the Maillard reaction under heat-stress
      storage. In this study, we investigate the production of browning high-molecular
      compounds and discuss the relationships among the respective contents of these
      compounds, amino acids and reducing sugars and the colouration (delta E*(ab)) of
      TJ-23 under heat-stress conditions. As a result of the investigation, it was
      found that peaks corresponding to the high-molecular compounds were separated
      from the heat-stressed samples of TJ-23 at each molecular weight of about 5,000,
      1,0000, 230,000 and 3,000,000, and especially the latter two peaks increased in
      areas up to about 11 times and 4 times at 60 degrees C from 10 through 90d
      respectively. At the same time, it was confirmed that the content of amino acids
      and reducing sugars decreased with an increase in storage temperature at 10d.
      Furthermore, it has become apparent that the content of high molecular compounds
      was correlated with colour differences (delta E*(ab)) of heat-stressed TJ-23, and
      then those compounds were related to the decreases of glucose and amino acids.
      From these results, we confirmed that the browning of Kampo medicines extract
      granules might proceed partially by Maillard reaction under higher temperature
      and/or longer time conditions.

PMID- 9019531
TI  - Biennial meeting of the World Institute of Ecology and Cancer and the European
      Institute of Ecology and Cancer. Bursa, Turkey, October 6-8, 1995. Abstracts.

PMID- 9019532
TI  - Carbachol-induced [Ca2+]i oscillations in single smooth muscle cells of guinea
      pig ileum.
AB  - 1. Changes in cytosolic Ca2+ concentration ([Ca2+]i) produced by carbachol (CCh)
      were measured in single smooth muscle cells of guinea-pig ileum using a Ca(2+)
      sensitive fluorescent dye, fura-2, to clarify the underlying mechanisms of
      muscarinic [Ca2+]i oscillations. 2. Half of the cells, when exposed to 0.2 microM
      CCh, exhibited repeated changes in [Ca2+]i giving a serrated appearance. The
      oscillatory changes in [Ca2+]i were very similar to those evoked by increasing
      extracellular K(+) concentration ([K+]o) to 30 mM, which were abolished by
      removal of extracellular Ca2+, nifedipine and La3+, but remained unchanged after
      depletion of internal Ca2+ stores with cyclopiazonic acid, thapsigargin and
      ryanodine. 3. Every individual [Ca2+]i oscillation was just like a [Ca2+]i
      increase generated spontaneously in about 8% of cells or triggered by an action
      potential evoked by a current pulse in current-clamped cells. 4. In the remaining
      half of the cells exposed to 0.2 microM CCh, slower [Ca2+]i oscillations were
      elicited and every individual [Ca2+]i oscillation was always preceded by the fast
      brief increase in [Ca2+]i. 5. [Ca2+]i oscillations elicited by 2 microM CCh were
      temporally and functionally distinct from those induced by high [K+]o. They were
      more or less regular in the periodicity and pattern, comprised pacemaker
      potential-like [Ca2+]i increases or sinusoidal types of [Ca2+]i increases, and
      could be elicited even in 100 mM K+(o). 6. Removal of extracellular Ca2+ or
      application of nifedipine, methoxyverapamil (D600), diltiazem or La3+ during CCh
      (2 micro M)-induced [Ca2+]i oscillations caused them to disappear. In cells i
      which internal Ca2+ stores were depleted, 2 microM CCh did not evoke [Ca2+]i
      oscillations but occasionally induced single or repeated generation of the
      increase in [Ca2+]i with a serrated appearance. 7. The results indicate that CCh
      can induce two types of [Ca2+]i oscillation in guinea-pig ileal smooth muscle
      cells; one arises from Ca2+ influx associated with action potential discharges
      and the other from periodic release of Ca2+ from internal stores. The latter
      [Ca2+]i oscillation requires extracellular Ca2+ to sustain it.

PMID- 9019533
TI  - Ca2+ clearance mechanisms in isolated rat adrenal chromaffin cells.
AB  - 1. Intracellular Ca2+ clearance mechanisms were studied in rat adrenal chromaffin
      cells, by measuring slow tail currents through small-conductance Ca(2+)-activated
      K+ channels and using indo-1 photometry following depolarization-induced Ca2+
      loading. 2. Following several-hundred millisecond depolarizations, [Ca2+]i
      decayed in three phases. An initial fast decay was followed by a long-lasting,
      low plateau, then [Ca2+]i returned to the resting level slowly. 3. Replacement of
      external Na+ moderately slowed [Ca2+]i decay, indicating a contribution of plasma
      membrane Na(+)-Ca2+ exchange. 4. Raising external pH or application of
      extracellular Eosin of La3+ prolonged slow tail currents, indicating a
      contribution of plasma membrane Ca(2+)-ATPase to Ca2+ clearance. 5. Ca(2+)
      induced Ca2+ release from caffeine-sensitive stores occurred during
      depolarization. 6. Inhibition of endoplasmic reticulum Ca(2+)-ATPase had little
      effect on Ca2+ clearance. 7. Slow tail currents and [Ca2+]i decay following 0.2 -
      2 s depolarizations were much prolonged by mitochondrial inhibition with carbonyl
      cyanide m-chlorophenylhydrazone (CCCP) or Ruthenium Red, which abolished the
      initial rapid decay and plateau of [Ca2+]i. 8. In conclusion, mitochondrial Ca2+
      uptake plays a major role in Ca2+ clearance by rapidly and reversibly
      sequestering Ca2+ during depolarization-evoked Ca2+ loads.

PMID- 9019534
TI  - Voltage-dependent calcium currents and cytosolic calcium in equine airway
      myocytes.
AB  - 1. The relationship between voltage-dependent calcium channel current (I(Ca)) and
      cytosolic free calcium concentration ([Ca2+]i) was studied in fura-2 AM-loaded
      equine tracheal myocytes at 35 degrees C and 1.8 mM Ca2+ using the nystatin patch
      clamp method. The average cytosolic calcium buffering constant was 77 +/- 3 (n =
      14), and the endogenous calcium buffering constant component is likely to be
      between 15 and 50. 2. I(Ca) did not evoke significant calcium-induced calcium
      release (CICR) since (i)[Ca2+]i scaled with the integrated I(Ca) over the full
      voltage range of evoked calcium currents, (ii) increases in [Ca2+]i associated
      with I(Ca) were consistent with cytoplasmic buffering of calcium ions entering
      through voltage-dependent calcium channels (VDCCs) only, (iii) there was a fixed
      instantaneous relationship between transmembrane calcium flux (J(Ca)) and the
      change in cytosolic free calcium concentration (delta [Ca2+]i) during I(Ca), (iv)
      caffeine (8 mM) triggered 8-fold higher calcium transients than I(Ca), and (v)
      I(Ca) evoked following release of intracellular calcium by caffeine resulted in
      an equivalent delta[Ca2+]i-J(Ca) relationship. 3. The time constant (T) for the
      decay in [Ca2+]i was 8.6 +/- 1.5 s (n = 8) for single steps and 8.6 +/- 1.1 s (n
      = 13) following multiple steps that increased [Ca2+]i to much higher levels.
      Following application of caffeine (8 mM), however, [Ca2+]i decay was enhanced (T
      = 2.0 +/- 0.2 s, n = 3). The rate of [Ca2+]i decay was not voltage dependent, was
      not decreased in the absence of extracellular Na+ ions, and no pump current was
      detected. 4. We conclude that under near physiological conditions, neither CICR
      nor Na(+)-Ca2+ exchange play a substantial role in the regulation of I(Ca)
      induced increases in [Ca2+]i, and that, even following release of intracellular
      calcium by caffeine, Na(+)-Ca2+ exchange does not play an appreciable role in the
      removal of calcium ions from the cytosol.

PMID- 9019535
TI  - Modulation of Ca2+ channel activity by ATP metabolism and internal Mg2+ in guinea
      pig basilar artery smooth muscle cells.
AB  - 1. Single smooth muscle cells were isolated from the basilar artery of the guinea
      pig and, within 10 h, inward currents through voltage-gated Ca2+ channels were
      recorded using the amphotericin or conventional whole-cell voltage-clamp
      techniques. 2. In amphotericin whole-cell recordings, bath application of 2,4
      dinitrophenol (DNP, an uncoupler of mitochondrial ATP production) induced an
      initial stimulation (14% increase in 5 of 11 cells) and then pronounced
      inhibition (50% decrease in 9 of 11 cells within 9.5 min) of voltage-dependent
      Ca2+ current (I(Ca)) elicited by depolarizing to +10 mV in 1.5 mM extracellular
      Ca2+ solution. By contrast, inhibition of glycolysis by replacing glucose in the
      bath with 2-deoxy-D-glucose had no effect. 3. Na+ current through Ca2+ channels
      (I[(Ca)(Na)]) recorded in the absence of extracellular divalent cations also
      responded to DNP, again with stimulation followed by inhibition of current. The
      stimulation of I[(Ca)(Na)] was associated with a leftward shift of the Ca2+
      channel activation curve which averaged -9 mV. A combination of 2-deoxy-D
      glucose, mannoheptulose and 3-0-methyl-glucose had only minor effects on
      I[(Ca)(Na)], whereas rotenone had an effect similar to that of DNP in six of
      eight cells. 4. The amplitude of I[(Ca)(Na)] in conventional whole-cell
      recordings was not different from that in amphotericin whole-cell recordings,
      even without ATP in the recording pipette and with metabolic poisons in the bath
      solution. Furthermore, attempts to dephosphorylate the Ca2+ channels in ATP-free
      conditions did not prevent I[(Ca)(Na)], and a high concentration of Mg-ATP with
      or without a phosphorylation-supporting medium in the recording pipette did not
      increase its amplitude. 5. In the absence of ATP, Mg2+ inhibited whole-cell
      I[Ca)(Na)] with a K(d) of about 100 mu M at -10 mV and induced a leftward shift
      of the Ca2+ channel activation curve. When ATP and a phosphorylation-supporting
      medium were in the recording pipette the blocking effect of free Mg2+ was reduced
      but the shift in the Ca2+ channel activation curve was unaffected. 6. From these
      data it is suggested that inhibition of mitochondrial, but not glycolytic, ATP
      production has stimulatory and inhibitory effects on voltage-gated Ca2+ channels
      of basilar artery smooth muscle cells. Effects of intracellular Mg2+ on the Ca2+
      channels were modulated by ATP and mimicked the effects of metabolic poisoning by
      DNP. A hypothesis is discussed in which the intracellular free Mg2+ concentration
      may be a key factor coupling ATP production to Ca2+ channels.

PMID- 9019536
TI  - Neurokinin A and Ca2+ current induce Ca(2+)-activated Cl(-) currents in guinea
      pig tracheal myocytes.
AB  - 1. Membrane currents were recorded by a patch clamp technique in guinea-pig
      tracheal myocytes, using the whole cell mode with Cs(+) internal solution. 2.
      Both neurokinin A (NKA, 1 mu M) and caffeine (10 mM) evoked Ca(2+)-activated Cl-
      currents (I[Cl(Ca)]) transiently. In Ca(2+)-free bathing solution, the first
      application of NKA or caffeine elicited I[Cl(Ca)] but the second application of
      these substances failed to activate it. In addition, pretreatment with ryanodine
      in the presence of caffeine abolished the response to both NKA and caffeine
      whilst heparin (200 mu g ml(-1)) only blocked the NKA-induced response. I[Cl(Ca)]
      was also elicited by inositol 1,4,5-trisphosphate (IP(3)). 3. Command voltage
      pulses positive to 0 mV from a holding potential of -60 mV activated the voltage
      dependent L-type Ca2+ current (I(Ca,L)) and late outward current. Upon
      repolarization to the holding potential, slowly decaying inward tail currents
      were recorded. The outward current during the depolarizing pulses and the inward
      tail current were enhanced by Bay K 8644, but completely blocked by Cd2+ or
      nifedipine. Replacement of external Ca2+ with Ba2+, removal of Ca2+ from the bath
      solution, or inclusion of EGTA (5 mM) in the patch pipette, also led to abolition
      of these currents, indicating that they were Ca2+ dependent, and that Ca2+ influx
      due to I(Ca,L) activated the currents. 4. When [Cl(-)](O) or [Cl(-)](i) was
      changed, the reversal potential (E(rev)) of the Ca2+-activated currents shifted,
      thus behaving like a Cl(-)-selective ion channel as predicted by the Nernst
      equation. DIDS (1 mM) completely abolished the currents, also suggesting that
      they were I[Cl(Ca)]. 5. NKA (1 mu M) and caffeine (30 mM) transiently activated
      I[Cl(Ca)], and after that both agents markedly reduced I[Cl(Ca)] induced by
      I(Ca,L). This is probably due to sarcoplasmic reticulum (SR) Ca2+ release induced
      by NKA or caffeine, followed by inhibition of the Ca(2+)-induced Ca2+ release
      from the SR. 6. The present results indicate that I[Cl(Ca)] can be activated by
      SR Ca2+ release due to NKA or caffeine (through IP(3) or ryanodine receptors) as
      well as by Ca2+ influx due to I(Ca,L). It also suggests that activation of
      I[Cl(Ca)] by NKA may be mediated by the production of IP(3), which releases Ca2+
      from the SR.

PMID- 9019537
TI  - Actin microfilament disrupters enhance K(ATP) channel opening in patches from
      guinea-pig cardiomyocytes.
AB  - 1. To determine whether actin filament networks are associated with the
      regulation of ATP-sensitive K+ (K(ATP)) channel activity, single channel currents
      were measured in the inside-out configuration, and cytoskeletal disrupters
      applied to the internal side of patches excised from guinea-pig ventricular
      myocytes. 2. Treatment of patches with DNase I (10-200 micrograms ml(-1)), which
      forms complexes with G-actin and prevents actin filament formation, antagonized
      the ATP-induced inhibition of K(ATP) channels. 3. In the absence of ATP, DNase I
      did not increase K(ATP) channel activity. 4. When denatured by boiling or co
      incubated with purified actin subunits (200 mu g ml(-1)), DNase I(100 mu g ml(
      1)) did not antagonize the ATP-induced inhibition of K(ATP) channels. 5. The
      DNase I-induced decrease in the sensitivity of K(ATP) channels towards ATP
      induced inhibition was partially restored by addition of purified actin subunits
      (200 micrograms ml(-1)). 6. Cytochalasin B (10 microM), another actin filament
      disrupter, but neither taxol nor nocodazole (30-100 microM), two antimicrotubule
      agents, enhanced K(ATP) channel activity in the presence of ATP. 7. Hence, actin
      filament disrupters can attenuate the ATP-dependent inhibitory gating of K(ATP)
      channels. This suggests that subsarcolemmal actin filament networks may be
      associated with the regulation of cardiac K(ATP) channels.

PMID- 9019538
TI  - Functional interaction between K(ATP) channels and the Na(+)-K(+) pump in
      metabolically inhibited heart cells of the guinea-pig.
AB  - 1. Transmembrane current through ATP-regulated K(+) channels (IK(ATP)) was
      measured in ventricular heart cells of the guinea-pig in the whole-cell and cell
      attached patch configurations under conditions of metabolic poisoning with the
      mitochondrial uncoupler 2,4-dinitrophenol (DNP). 2. Maintained exposure of the
      cells to DNP resulted in a transient appearance of whole-cell IK(ATP) When
      IK(ATP) had reached several nanoamps, blocking the forward-running Na(+)-K(+)
      pump with 0.5 mM strophanthidin decreased IK(ATP) after a delay. The time course
      of this decrease could be described by a single exponential function, which
      yielded a time constant(T)of 4.51+/- 1.89 s (n=8). 3. Hyperpolarization from 0 mV
      to -100 or -150 mV for 2 s caused IK(ATP) (measured at 0 mV) to decrease by 34.2
      +/- 14.1 % (n = 8) and 37.6 +/- 9.4% (n = 8), respectively. After the
      hyperpolarizing pulse, IK(ATP) returned to its higher initial level within a
      couple of seconds. 4. Driving the pump backwards by removing the extracellular
      K(+) ions caused the permanent disappearance of DNP-induced IK(ATP). 5.
      Application of 0.5 mM strophanthidin in the absence of external K(+) ions induced
      a transient increase in IK(ATP), as did washing out the glycoside (n = 5). 6.
      When pump action was inhibited by using Na(+), K(+)-free Tyrode solution (see
      Methods) in the bath, strophanthidin did not have a comparable direct effect on
      IK(ATP). 7. In cell-attached patches, strophanthidin applied via the bath caused
      a reduction in IK(ATP) with a similar time course to that in whole-cell
      experiments. This suggests that the interaction between the pump molecules and
      the K(ATP) channels is not restricted to closely neighbouring molecules. 8. The
      data support the hypothesis that [ATP] at the cytosolic face of the membrane may
      drop to practically zero, thereby passing an 'ATP window' in which the channels
      first open and then close, and that the submembrane [ATP] is readily controlled
      by the cytosolic [ATP].

PMID- 9019539
TI  - Extracellular K(+)-induced hyperpolarizations and dilatations of rat coronary and
      cerebral arteries involve inward rectifier K(+) channels.
AB  - 1. The hypothesis that inward rectifier K(+) channels are involved in the
      vasodilatation of small coronary and cerebral arteries (100-200 microm diameter)
      in response to elevated [K+]o was tested. The diameters and membrane potentials
      of pressurized arteries from rat were measured using a video-imaging system and
      conventional microelectrodes, respectively. 2. Elevation of [K+]o from 6 to 16 mM
      caused the membrane potential of pressurized (60 mmHg) arteries to hyperpolarize
      by 12-14 mV. Extracellular Ba(2+) (Ba2+(o)) blocked K(+)-induced membrane
      potential hyperpolarizations at concentrations (IC(50), 6 microM) that block
      inward rectifier K(+) currents in smooth muscle cells isolated from these
      arteries. 3. Elevation of [K+]o from 6 to 16 mM caused sustained dilatations of
      pressurized coronary and cerebral arteries with diameters increasing from 125 to
      192 microm and 110 to 180 microm in coronary and cerebral arteries, respectively.
      Ba2+(o) blocked K(+)-induced dilatations of pressurized coronary and cerebral
      arteries (IC50, 3-8 microM). 4. Elevated [K+]o-induced vasodilatation was not
      prevented by blockers of other types of K(+) channels (1 mM 4-aminopyridine, 1 mM
      TEA+, and 10 mu M glibenclamide), and blockers of Na(+)-K(+)-ATPase. Elevated
      [K+]o-induced vasodilatation was unaffected by removal of the endothelium. 5.
      These findings suggest that K+(o) dilates small rat coronary and cerebral
      arteries through activation of inward rectifier K(+) channels. Furthermore, these
      results support the hypothesis that inward rectifier K(+) channels may be
      involved in metabolic regulation of coronary and cerebral blood flow in response
      to changes in [K+]o.

PMID- 9019540
TI  - Proton sensitivity of the GABA(A) receptor is associated with the receptor
      subunit composition.
AB  - 1. Modulation of GABA(A) receptors by external H(+) was examined in cultured rat
      sympathetic neurones, and in Xenopus laevis oocytes and human embryonic kidney
      (HEK) cells expressing recombinant GABA(A) receptors composed of combinations of
      alpha 1, beta 1, beta 2, gamma 2S and delta subunits. 2. Changing the external pH
      from 7.4 reduced GABA-activated currents in sympathetic neurones. pH titration of
      the GABA-induced current was fitted with a pH model which predicted that H(+)
      interact with two sites (PK(a) values of 6.4 and 7.2). 3. For alpha 1 beta 1
      GABA(A) receptors, low external pH (< 7.4) enhanced responses to GABA. pH
      titration predicted the existence of two sites with PK(a) values of 6.6 and 7.5.
      The GABA concentration-response curve was shifted to the left by low pH and non
      competitively inhibited at high pH (> 7.4). 4. alpha 1 beta 1 gamma 2S receptor
      constructs were not affected by external pH, whereas exchanging the beta 1
      subunit for beta 2 conferred a sensitivity to pH, with predicted PK(a) values of
      5.16 and 9.44. 5. Low pH enhanced the responses to GABA on alpha 1 beta 1 delta
      subunits, whilst high pH caused an inhibition (PK(a) values of 6.6 and 9.9). The
      GABA concentration-response curves were enhanced (pH 5.4) or reduced (pH 9.4)
      with no changes in the GABA EC(50). 6. Immunoprecipitation with subunit and
      epitope-specific antisera to alpha 1, beta 1 and delta subunits demonstrated that
      these subunits could co-assemble in cell membranes. 7. Expression of alpha 1 beta
      1 gamma 2S delta constructs resulted in a 'bell-shaped' pH titration
      relationship. Increasing or decreasing external pH inhibited the responses to
      GABA. 8. The pH sensitivity of recombinant GABA(A) receptors expressed in HEK
      cells was generally in accordance with data accrued from Xenopus oocytes.
      However, rapid application of GABA to alpha 1 beta 1 constructs at high pH (>
      7.4) caused an increased peak and reduced steady-state current, with a
      correspondingly increased rate of desensitization. 9. Modulation of GABA(A)
      receptor function was apparently unaffected by the internal pH. Moreover, pH
      values between 5 and 9.5 did not significantly affect the charge distribution on
      the zwitterionic GABA molecules. 10. In conclusion, this study demonstrates that
      external pH can either enhance, have little effect, or reduce GABA-activated
      responses, and this is apparently dependent on the receptor subunit composition.
      The potential importance of H(+) sensitivity of GABA(A) receptors is discussed.

PMID- 9019541
TI  - Subtype-specific regulation of recombinant NMDA receptor-channels by protein
      tyrosine kinases of the src family.
AB  - 1. Tyrosine kinases regulate NMDA receptor-channel activity in cultured neurons,
      and NMDA receptor subunits are tyrosine phosphorylated in the brain. 2.
      Heteromeric NMDA receptor-channels were transiently expressed in human embryonic
      kidney (HEK) 293 cells and glutamate (100 microM)-activated whole-cell currents
      (500 ms) were studied when tyrosine kinases of the src gene family were included
      in the pipette solution. 3. Glutamate-activated currents (evoked every 20 s for
      up to 20 min) were increased by src and fyn kinases without affecting the
      desensitization and deactivation kinetics in NR1-NR2A but the kinases had no
      effects in NR1-NR2B, NR1-NR2C and NR1-NR2D receptor-channels, suggesting that a
      phosphorylation site in NR2A is targeted. 4. In a mutant channel consisting of
      NR1 and a C-terminal deletion mutant of NR2A (NR2A delta C), src and fyn kinases
      lost their potentiating effects indicating that the phosphorylation of
      tyrosine(s) in the C-terminal domain of NR2A affects the current flux through
      native NMDA receptor-channels.

PMID- 9019542
TI  - Detection and modulation of acetylcholine release from neurites of rat basal
      forebrain cells in culture.
AB  - 1. Nicotinic acetylcholine (ACh) receptor-rich patches prepared from rat myotubes
      were used as focal ACh detectors to record the release of ACh from magnocellular
      basal forebrain (MBF) neurones from 11- to 14-day-old postnatal rats maintained
      in dissociated cell culture. 2. An action potential generated by intracellularly
      stimulating the MBF cell soma through a patch electrode induced a brief (mean
      tau(decay), 6.3 ms) short latency (1.35-5.1 ms; median 3.1 ms) burst of nicotinic
      channel openings in the detector patch when the latter was positioned at discrete
      loci along the MBF neurites. Detected ACh concentrations ranged from
      approximately 480 nM to > 50 microM. Concentrations increased markedly during the
      first 14 days in vitro and were inversely related to response latency. 3. Sites
      of release were generally confined to the more proximal neurites within 100
      microm of the cell body and were invariably associated with the presence of small
      (2-3 microm diameter) phase-dark puncta located at discrete intervals along the
      length of the neurites or at points where short collaterals branched from the
      main process. Release was never detected from the cell soma except under extreme
      non-physiological conditions but could occasionally be elicited from growth cones
      at the ends of the shorter thicker neurites in the absence of a target cell. 4.
      Evoked release was abolished by tetrodotoxin (0.5 microM) and by superfusing with
      low Ca(2+)-high Mg(2+)-containing solutions (0.25 mM Ca(2+), 5 mM Mg(2+)).
      Myotube patch responses were antagonized by d-tubocurarine (3 microM). 5.
      Muscarine (10 microM) inhibited release by 70 +/- 3% (n = 12 cells). This effect
      was antagonized by 100 nM methoctramine but not by 100 nM pirenzepine, indicating
      that it was mediated by M(2) muscarinic ACh receptors. 6. These results indicate
      that ACh release from the processes of magnocellular cholinergic basal forebrain
      neurones arises from highly specialized and discrete sites, and that it can be
      inhibited through activation of muscarinic receptors. It is suggested that the
      latter results from inhibition of presynaptic Ca(2+) channels and that it might
      be responsible for feedback autoinhibition of ACh release from cortical afferents
      of nucleus basalis neurones in vivo.

PMID- 9019543
TI  - Modulation of inwardly rectifying currents in rat sympathetic neurones by
      muscarinic receptors.
AB  - 1. Intracellular recordings were made from rat sympathetic neurones in isolated
      superior cervical ganglia (SCG), coeliac ganglia (CG), and superior mesenteric
      ganglia (SMG). 2. Following classification of the firing properties of these
      neurones as either 'phasic' or 'tonic', single-electrode voltage-clamp recordings
      of the inwardly rectifying current were performed. The inward rectifier
      conductance was 6.4 times larger in tonic neurones than in phasic neurones. 3.
      The basic features of the inward rectifier in sympathetic neurones were similar
      to those of the classic inward rectifier described in several neuronal and non
      neuronal preparations. The properties of the native channel were also similar to
      a subset of recently cloned inwardly rectifying channels. The reversal potential
      and the slope conductance were both dependent on external potassium ion
      concentration. The conductance was blocked by low concentrations of external
      Ba(2+) and Cs(+) ions. 4. A striking feature of the inward rectifier in
      sympathetic neurones was its modulation by muscarine. Application of 20 microM
      muscarine produced a mean 78 +/- 1.4% inhibition of the current. From dose
      response curves for muscarine a mean dissociation constant of K(D) = 1.95 +/- 0.2
      microM was determined. Schild plot analysis using the competitive antagonists
      pirenzepine and himbacine indicated that the effect of muscarine was mediated by
      the M(1) class of muscarinic receptors. 5. The inward rectifier was also
      inhibited by repetitive nerve stimulation which produced a block of the
      conductance similar to that seen in response to bath-applied muscarine. The onset
      of inhibition was relatively slow, 20-30 s, suggesting that it is mediated by a
      soluble second messenger pathway.

PMID- 9019544
TI  - Muscarinic receptors mediating depression and long-term potentiation in rat
      hippocampus.
AB  - 1. Two concentration-dependent effects of the muscarinic agonist carbachol (CCh)
      were characterized in submerged slices of rat hippocampus using extracellular
      recordings of excitatory postsynaptic potentials (EPSPs): muscarinic long-term
      potentiation (LTP(m)) and depression. 2. LTP(m) of the EPSP slope was seen
      following long exposure (20 min) of the slice to low concentrations of CCh (0.2
      0.5 microM). This LTP(m) was not accompanied by a change in the size of the
      afferent fibre volley or by a change in paired-pulse potentiation, consistent
      with a postsynaptic locus of CCh action. 3. Intracellular recordings from voltage
      clamped neurons of inward current evoked by iontophoretically applied alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA)
      revealed that, while cellular responses to NMDA rose transiently upon superfusion
      with 0.5 microM CCh, responses to AMPA increased gradually and remained
      potentiated after washout of CCh. 4. LTP(m) is mediated by an M2 muscarinic
      receptor. Two M2 muscarinic receptor antagonists, methoctramine and AFDX-116,
      blocked LTP(m). The M2 agonist oxotremorine induced LTP(m) at low agonist
      concentrations. None of the M1 and M3 receptor agonists and antagonists tested
      affected LTP(m). 5. Muscarinic fast onset depression of the EPSP was seen in
      response to higher concentrations of CCh (2-5 mu M). This depression was
      accompanied by an increase in paired-pulse potentiation, indicating a possible
      presynaptic locus of action. The M3 muscarinic receptor antagonist 4
      diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) blocked the muscarinic
      depression of the EPSP slope. M1, M2 and M4 muscarinic antagonists did not block
      this response. 6. Blockade of the muscarinic depression by 4-DAMP did not uncover
      a suppressed LTP(m). However, addition of picrotoxin facilitated the expression
      of LTP(m) induced by high concentrations of CCh, indicating an involvement of
      interneurons in regulation of LTP(m). 7. Cholinergic denervation produced by
      fimbria-fornix transection resulted in supersensitivity of both M2- and M3
      mediated effects, indicating that the receptors mediating these effects are not
      located on presynaptic cholinergic fibres. In the presence of 4-DAMP and
      picrotoxin the dose-response curve for CCh-induced effects in slices from
      lesioned animals was shifted to the left relative to that of normal animals,
      indicating a supersensitivity of both receptor types.

PMID- 9019545
TI  - The role of the A(2A) adenosine receptor subtype in functional hyperaemia in the
      hindlimb of anaesthetized cats.
AB  - 1. The present study was designed to investigate the contribution of the A(2A)
      adenosine receptor subtype in the functional hyperaemia response during muscle
      contraction. 2. In cats anaesthetized with sodium pentobarbitone and breathing
      spontaneously following tracheotomy, the left sciatic and femoral nerves were
      electrically stimulated at 3 Hz for 20 min to induce muscle contraction, and
      hindlimb blood flow was measured with a flow probe. The contribution of the A(2A)
      adenosine receptor subtype was assessed using ZM 241385, a potent and selective
      A(2A) adenosine receptor antagonist. 3. In a control group, the muscle isometric
      tension measured in the extensor digitorum longus-tibialis anterior muscle group
      was 6.64 +/- 0.66 kg (100 g muscle mass)(-1) and hindlimb vascular conductance
      was 0.22 +/- 0.03 ml mmHg(-1)(kg body mass)(-1) at 20 min of contraction.
      Administration of vehicle did not affect these parameters upon a second
      contraction period: 6.31 +/- 0.61 kg (100 g muscle mass)(-1) and 0.23 +/- 0.03 ml
      mmHg(-1) (kg body mass)(-1), respectively. Total hindlimb conductance during
      contraction was unaffected (5.5 +/- 3.7% decrease). 4. ZM 241385 (1.0 mg kg(-1))
      did not alter the amount of force produced by the muscle at 20 min of
      contraction. Hindlimb conductance response was reduced by 27.1 +/- 4.8% following
      the A(2A) selective adenosine receptor antagonist, similar to that observed with
      the non-selective antagonist 8-phenyltheophylline. 5. These results show that
      adenosine acting at the A(2A) subtype receptor can contribute up to 30% of the
      functional hyperaemia response in the hindlimb of anaesthetized cats.

PMID- 9019546
TI  - Component characteristics of the vectorial transport system for taurine in
      isolated bovine retinal pigment epithelium.
AB  - 1. A wide range of substrate concentrations (5-1600 microM) were used to screen
      for the presence of systems capable of transporting taurine into isolated and
      free-floating samples of bovine retinal pigment epithelium (RPE). Both high and
      low affinity systems displaying Michaelis-Menten saturation kinetics were
      identified. The high affinity system was characterized by a K(m) of 23 microM and
      a V(max) of 86.7 pmol (5 min)(-1) (4 mm disc of tissue sample)(-1). Similarly,
      the low affinity system was characterized by a K(m) of 507 microM and a V(max) of
      344 pmol (5 min)(-1)(4 mm disc)(-1). 2. Ussing-type incubation chambers and
      double-label radiotracer techniques were used to assess the presence of specific
      taurine carriers on apical and basolateral surfaces of the RPE. High affinity
      carriers were shown to be present on both surfaces and the kinetic constants
      (K(m) and V(max)) for apical and basolateral systems were determined as 23.2
      microM and 34.8 pmol (5 min)(-1) (4 mm disc)(-1) and 29 microM and 54.7 pmol (5
      min)(-1)(4 mm disc)(-1), respectively. Both these high affinity systems were
      sodium dependent with a Hill coefficient of about 2.0 indicating that two sodium
      ions are required for the translocation of one molecule of taurine. The low
      affinity system was unevenly distributed over the two surfaces of the RPE,
      basolateral capacities being roughly twofold higher. The basolateral system was
      totally insensitive to sodium whereas the apical one with 50% sodium sensitivity
      suggested the presence of low affinity carrier heterogeneity. 3. A temperature
      dependent mechanism for the release of pre-loaded taurine from bovine RPF was
      also demonstrated. 4. The effect of [K+]o trans-RPF gradients on the vectorial
      transport of taurine across the isolated preparation was also investigated. The
      results demonstrated that the direction and magnitude of taurine transport could
      be controlled by physiological variations in the extracellular concentration of
      potassium. 5. The determined kinetic parameters of the carriers were used to
      construct a working model of the vectorial pathway for the translocation of
      taurine across bovine RPE. This estimated the level of free intracellular taurine
      to be in the micromolar range. However, direct measurements of total RPE taurine
      by high performance liquid chromatography showed levels of 19.5 +/- 3.6 mM
      indicating that the major taurine pool in bovine RPE exists in the bound form.
      The model also showed that the magnitude and direction of net transport was a
      function of the transepithelial taurine gradient.

PMID- 9019547
TI  - The hypothesis of the uniqueness of the oculomotor neural integrator: direct
      experimental evidence in the cat.
AB  - 1. As far as horizontal eye movements are concerned, the well-known hypothesis,
      not yet experimentally proved, of the common neural integrator states that the
      eye-position signal is generated by a common network, regardless of the type of
      versional movement. The aim of this study was to evaluate the validity of this
      hypothesis by checking whether the sensitivity to eye position of the neurones of
      the nucleus prepositus hypoglossi (NPH) (the main component of the system
      integrating the different incoming velocity signals) would be the same regardless
      of the type of versional movement. 2. The discharge of sixty-five NPH neurones
      was recorded in the alert cat during spontaneous eye movements made in the light
      and in response to sinusoidal rotations of the head in complete darkness. 3. For
      each NPH neurone, the sensitivity to eye position was determined from
      measurements carried out during intersaccadic fixation. The discharge rate of the
      studied neurone was plotted against eye position. The slope of the resulting
      regression line gave the sensitivity (measured during intersaccadic fixation in
      the light) of the neurone to eye position, which was termed K(f). 4. A new method
      was developed to measure the sensitivity to eye position (K(v)) of neurones
      during vestibular slow phases. The difficulty came from the fact that, during
      slow phases, eye velocity and eye position changed simultaneously and that each
      of those two variables could influence neuronal activity. For each neurone, the
      instantaneous firing rate was measured each time the eye passed through a given
      position during any slow phase generated during any vestibulo-ocular reflex. At a
      given position, the discharge rate of the neurone under study was plotted against
      the eye velocity. From the resulting linear regression line, two interesting
      values were obtained: its slope, corresponding to the sensitivity of the neurone
      to eye velocity, R(v), (at that given eye position) and its 'y'-intercept, F(0),
      the interpolated firing rate when the eye velocity was zero. This procedure was
      repeated for different eye positions. The values of F(0) were then plotted
      against the eye positions. The slope of the resulting regression line gave the
      sensitivity (measured during vestibular stimulation) of the neurone to eye
      position, which was termed K(v). 5. The errors on the individual values of K(f)
      and K(v) were assessed in order to allow a statistical comparison at the single
      unit level. 6. We found that, for each of our sixty-five neurones, the
      sensitivity to eye position measured during intersaccadic fixation in the light
      was equal to the sensitivity to eye position measured during the vestibulo-ocular
      reflex (VOR) elicited in complete darkness. We conclude that our results favour
      the hypothesis of a unique horizontal oculomotor integrator for all versional
      movements.

PMID- 9019548
TI  - Respiratory activity in the facial nucleus in an in vitro brainstem of tadpole,
      Rana catesbeiana.
AB  - 1. In studies of the central neural control of breathing, little advantage has
      been taken of comparative approaches. We have developed an in vitro brainstem
      preparation using larval Rana catesbeiana which generates two rhythmic neural
      activities characteristic of lung and gill ventilation. Based on the pattern of
      the facial (VII) nerve activity both lung and gill rhythm-related respiratory
      cycles were divided into three distinct phases. The purpose of this study was to
      characterize and classify membrane potential trajectories of respiratory
      motoneurons in the VII nucleus at intermediate stages (XII-XVII) of development.
      2. Seventy-five respiratory-modulated neurons were recorded intracellularly
      within the facial motor nucleus region. Their resting membrane potential was
      between -40 and -80 mV. Sixty of them were identified as VII motoneurons and
      fifteen were non-antidromically activated. Membrane potentials of fifty-six of
      the seventy-five neurons were modulated with both lung (5-27 mV) and gill rhythms
      (3-15 mV) and the remaining nineteen neurons had only a modulation with lung
      rhythmicity (6-23 mV). No cells with gill modulation alone were observed. 3. All
      of the cells modulated with lung rhythmicity had only phase-bound depolarizing or
      hyperpolarizing membrane potential swings which could be categorized into four
      distinct patterns. In contrast, of the fifty-six cells modulated with gill
      rhythmicity, thirty-two were phasically depolarized during distinct phases of the
      gill cycle (four patterns were distinguished), whereas the remaining twenty-four
      were phase spanning with two distinct patterns. The magnitudes of lung and gill
      modulations were proportionally related to each other in the cells modulated with
      both rhythms. 4. In all sixteen neurons studied, a reduction or a reversal of
      phasic inhibitory inputs during a portion of the lung or gill respiratory cycle
      was observed following a negative current or chloride ion (Cl-) injection. The
      phasic membrane resistance modulation in relation to the gill rhythm was analysed
      in six neurons and a relative decrease in the somatic membrane resistance (0.7
      8.1 M omega) was detected during the periods of hyperpolarization. 5. We propose
      that, at these intermediate stages of development: (a) both gill and lung
      respiratory oscillations in motoneurons are generated by respiratory premotor
      neurons having only a few distinct activity patterns; (b) these patterns
      delineate distinct portions of the centrally generated respiratory cycles; and
      (c) phasic synaptic inhibition, mediated by Cl-, contributes to shaping the
      membrane potential trajectories of respiratory motoneurons.

PMID- 9019549
TI  - Role of chloride-mediated inhibition in respiratory rhythmogenesis in an in vitro
      brainstem of tadpole, Rana catesbeiana.
AB  - 1. The isolated brainstem of larval Rana catesbeiana maintained in vitro
      generates neural bursts that correspond to the lung and gill ventilatory activity
      generated in the intact specimen. To investigate the role of chloride channel
      dependent inhibitory mechanisms mediated by GABA(A) and/or glycine receptors on
      fictive lung and gill ventilation, we superfused the isolated brainstems with
      agonists, antagonists (bicuculline and/or strychnine) or a chloride-free solution
      while recording multi-unit activity from the facial motor nucleus. 2. Superfusion
      with the agonists (GABA or glycine) produced differential effects on frequency,
      amplitude and duration of the neural bursts related to lung and gill ventilation.
      At a GABA or glycine concentration of 1.0 mM, fictive gill bursts were abolished
      while fictive lung bursts persisted, albeit with reduced amplitude and frequency.
      3. At the lowest concentrations used (1.0-2.5 microM), the GABA(A) receptor
      antagonist bicuculline produced an increase in the frequency of lung bursts. At
      higher concentrations (5.0-2.0 microM) bicuculline produced non-specific
      excitatory effects. The glycine antagonist strychnine, at concentrations lower
      than 5.0 microM, caused a progressive decrease in the frequency and amplitude of
      the gill bursts and eventually abolished the rhythmic activity. At higher
      concentrations (7.5 microM), non-specific excitatory effects occurred.
      Superfusion with bicuculline (10 microM) and strychnine (5 microM) combined
      abolished the neural output for gill ventilation but increased the frequency,
      amplitude and duration of lung bursts. 4. Superfusion with Cl(-)-free solution
      also abolished the rhythmic neural bursts associated with gill ventilation, while
      it significantly increased the amplitude (228 +/- 51%; P < 0.05) (mean +/-
      S.E.M.) and duration of the lung bursts (3.5 +/- 0.1 to 35.3 +/- 3.7 s; P < 0.05)
      and improved the regularity of their occurrence. 5. We conclude that different
      neural systems generate rhythmic activity for lung and gill ventilation. Chloride
      mediated inhibition may be essential for generation of neural bursts associated
      with gill ventilation. In contrast, the burst associated with lung ventilation
      can be generated in the absence of Cl(-)-mediated inhibition although the latter
      plays a role in shaping the normal lung burst.

PMID- 9019550
TI  - Excitatory amino acid-mediated chemoreflex excitation of respiratory neurones in
      rostral ventrolateral medulla in rats.
AB  - 1. In anaesthetized rats, extracellular and intracellular recordings were made
      from 119 respiratory neurones in the rostroventrolateral reticular nucleus (RVL)
      of the medulla oblongata. 2. Two types of active respiratory neurones were
      detected in RVL: expiratory (E) and pre-inspiratory (Pre-I), based on the
      relationship between their discharge and that of the phrenic nerve. Some Pre-I
      but none of the E neurones could be antidromically excited from the C(3)-C(4)
      level of the spinal cord. 3. E and Pre-I neurones of RVL were excited by
      stimulation of the arterial chemoreceptors by a close arterial injection of
      sodium cyanide. The reflex excitation of RVL E neurones was preceded by increased
      phrenic nerve activity, while the excitation of RVL Pre-I neurones preceded the
      increases in phrenic nerve activity. 4. The chemoreflex excitation of the two
      types of RVL respiratory neurones as well as their resting discharge was
      abolished or significantly depressed by microionophoresis of kynurenate, a wide
      spectrum antagonist of excitatory amino acid receptors, while xanthurenate, an
      inactive analogue of kynurenate, was without effect. 5. In ventilated rats,
      bilateral microinjection into RVL of kynurenate, but not xanthurenate, abolished
      resting activity and chemoreflex excitation of phrenic nerve activity, whilst in
      spontaneously breathing rats, kynurenate microinjection into RVL produced apnea
      and silenced phrenic nerves. 6. We conclude: (a) chemoreflex excitation of the
      phrenic nerves is mediated by stimulating Pre-I neurones of RVL by excitatory
      amino acidergic inputs and (b) RVL Pre-I neurones may directly and/or indirectly
      excite spinal phrenic motor neurones and hence are involved in inspiratory
      rhythmogenesis.

PMID- 9019551
TI  - Postnatal development of the pattern of respiratory and cardiovascular response
      to systemic hypoxia in the piglet: the roles of adenosine.
AB  - 1. In 3-day-old and 3-week-old spontaneously breathing piglets anaesthetized with
      Saffan, we have studied ventilatory and cardiovascular responses evoked by 5 min
      periods of hypoxia (breathing 10 and 6% O2). 2. In 3-day-old piglets both 10 and
      6% O2 evoked an increase followed by a secondary fall in ventilation, a gradual
      tachycardia and a renal vasoconstriction, with an increase in femoral blood flow
      that was attributable to femoral vasodilatation. Arterial blood pressure rose
      initially but fell towards control values by the 5th minute of hypoxia. 3. The
      stable adenosine analogue 2-chloroadenosine (2-CA; 30 mg kg(-1) i.v.) evoked
      bradycardia and renal vasoconstriction, but had no effect on femoral vasculature.
      These responses were blocked by the adenosine receptor antagonist 8
      phenyltheophylline (8-PT; 8 mg kg(-1) i.v.). 8-PT also abolished the secondary
      fall in ventilation evoked by 10 and 6% O2 and the renal vasoconstriction evoked
      by 10% O2, but had no effect on the tachycardia, or on the femoral vascular
      response. 4. By contrast, in 3-week-old piglets both 10 and 6% O2 evoked a
      sustained increase in ventilation, tachycardia and a rise in arterial pressure
      with renal vasoconstriction, but no change in renal blood flow and substantial
      femoral vasodilatation with an increase in femoral blood flow. 2-CA evoked
      bradycardia and renal vasoconstriction, as in 3-day-old piglets, but also evoked
      pronounced femoral vasodilatation. 8-PT blocked these responses and the hypoxia
      induced femoral vasodilatation, but had no significant effect on other components
      of the hypoxia-induced response. 5. We propose that there is postnatal
      development of the ventilatory and cardiovascular responses evoked by systemic
      hypoxia and of the role of locally released adenosine in these responses: at 3
      days, adenosine released within the central nervous system and within the kidney
      is a major contributor to the secondary fall in ventilation and renal
      vasoconstriction respectively, whereas at 3 weeks, adenosine makes little
      contribution to the ventilatory response, or renal vasoconstriction, but is
      largely responsible for hypoxia-induced vaso-dilatation in skeletal muscle.

PMID- 9019552
TI  - The effects of locomotor-respiratory coupling on the pattern of breathing in
      horses.
AB  - 1. To investigate the effect of locomotor activity on the pattern of breathing in
      quadrupeds, ventilatory response was studied in four healthy horses during
      horizontal and inclined (7%) treadmill exercise at different velocities (1.4-6.9
      m s(-1)) and during chemical stimulation with a rebreathing method. Stride
      frequency (f(s)) and locomotor-respiratory coupling (LRC) were also
      simultaneously determined by means of video recordings synchronized with
      respiratory events. 2. Tidal volume (V(T)) was positively correlated with
      pulmonary ventilation (V(E)) but significantly different linear regression
      equations were found between the experimental conditions (P < 0.0001), since the
      chemical hyperventilation was mainly due to increases in V(T), whereas the major
      contribution to exercise hyperpnoea came from changes in respiratory frequency
      (f(R)). 3. The average f(R) at each exercise level was not significantly
      different from f(S), although there was not always a tight 1:1 LRC. At constant
      speeds, f(S) was independent of the treadmill slope and hence the greater V(E)
      during inclined exercise was due to increased V(T). 4. At any ventilatory level,
      the differences in breathing patterns between locomotion and rebreathing or
      locomotion at different slopes derived from different set points of the
      inspiratory off-switch mechanism. 5. The percentage of single breaths entrained
      with locomotor rhythm rose progressively and significantly with treadmill speed
      (P < 0.0001) up to a 1:1 LRC and was significantly affected by treadmill slope (P
      < 0.001). 6. A LRC of 1:1 was systematically observed at canter (10 out of 10
      trials) and sometimes at trot (5 out of 14) and it entailed (i) a 4- to 5-fold
      reduction in both V(T) and f(R) variability, and (ii) a gait-specific phase
      locking of inspiratory onset during the locomotor cycle. 7. It is concluded that
      different patterns of breathing are employed during locomotion and rebreathing
      due to the interference between locomotor and respiratory functions, which may
      play a role in the optimization and control of exercise ventilation in horses.

PMID- 9019553
TI  - Relationship of firing intervals of human motor units to the trajectory of post
      spike after-hyperpolarization and synaptic noise.
AB  - 1. Interspike interval distributions from human motor units of a variety of
      muscles were analysed to assess the role of synaptic noise in excitation. The
      time course of the underlying post-spike after-hyperpolarization (AHP) was
      deduced by applying a specially developed transform to the interval data.
      Different firing rates were studied both by varying the firing voluntarily, and
      by selecting subpopulations of spikes for a given firing rate from long
      recordings with slight variations in frequency. 2. At low firing rates the
      interval histograms had an exponential tail. Thus at long intervals, the
      motoneurone was randomly excited by noise and its post-spike AHP was complete.
      This contrasts with the firing produced by intracellular current injection in the
      cat, when the membrane potential increases linearly until threshold is reached.
      The interval histogram was therefore analysed with the aid of a model of synaptic
      excitation to deduce the mean 'trajectory' of membrane voltage in the last part
      of the interspike interval. 3. The computer model, described in the Appendix, was
      used to determine the effect of the mean level of membrane potential on the
      probability of a spike being excited, per unit time, during an on-going
      interspike interval. All variables were treated as voltages, with synaptic noise
      simulated by time-smoothed Gaussian noise. This enabled an interval distribution
      to be transformed into a segment of the underlying trajectory of the membrane
      potential; the potential was expressed in terms of the noise amplitude and the
      spike threshold. 4. At low firing rates, the equilibrium value of the membrane
      voltage trajectory lay well below threshold; the deviation typically corresponded
      to the standard deviation of the noise or more. The noise standard deviation was
      estimated to be about 2 mV. 5. With increasing mean firing rate, the near
      threshold portion of the trajectory obtainable from the histogram occurred
      earlier, was steeper and rose to a higher level. Trajectories for different
      firing rates fell on the same curve after shifting them vertically by varying
      amounts. The curve was taken to represent the AHP of the motoneurone and was
      closely exponential. The shift of the trajectory gave its mean synaptic drive.
      The duration of the AHP varied between units and was longer than average for
      units from soleus muscle. 6. Further modelling showed that summation of noise
      with the AHP can explain the well-known changes in discharge variability that
      occur as firing rate increases. 7. It is concluded that synaptic noise plays a
      major role in the excitation of tonically firing human motoneurones and that the
      noiseless motoneurone with a linear trajectory provides an inadequate model for
      the conscious human. This is of interest in relation to various standard measures
      of human motor unit activity such as short-term synchronization.

PMID- 9019554
TI  - Will the ethics chair please speak up?

PMID- 9019555
TI  - [Single dose toxicity studies of montirelin hydrate(NS-3) in mice, rats and
      dogs].
AB  - The single dose toxicity studies of montirelin hydrate (NS-3), a new drug for the
      treatment of disturbance of consciousness, were conducted in Slc:ddY mice, Slc:SD
      rats, and beagle dogs of both sexes. The drug was administered intravenously
      (i.v.) to mice, rats and dogs, and intramuscularly (i.m.) to mice and rats. The
      animals were observed for 14 days after administration. LD50 values were more
      than 500 mg/kg and 200 mg/kg in mice and rats, respectively, by the i.v. route,
      and more than 20 mg/kg in both animal species by the i.m. route. In dogs, the
      minimum lethal dose was more than 200 mg/kg by the i.v. route. Mice that received
      more than 125 mg/kg by the i.v. route showed tremor and a decrease in locomotor
      activity during administration and for 30 min thereafter. Mice that received more
      than 5 mg/kg by the i.m. route showed tremor 5 min after administration and for 2
      hr thereafter. Rats that received more than 50 mg/kg by the i.v. route showed
      tremor, and those that received 200 mg/kg by the same route showed a decrease in
      locomotor activity and ataxic gait, during and immediately after administration.
      Rats that received more than 5 mg/kg by the i.m. route showed tremor, and those
      that received 20 mg/kg by the same route showed salivation 5 min after
      administration and for 30 min thereafter. Dogs that received more than 12.5 mg/kg
      by the i.v. route revealed excitement, biting, vocalization, mydriasis,
      salivation, urination, defecation, licking chops, vomiting, increase in heart
      rate, panting, hyperthermia, tremor and conjunctival injection during
      administration and for 6 hr thereafter. The body weight, food consumption and
      water consumption, and pathological findings showed no changes attributable to
      the dosing of montirelin hydrate in any animal.

PMID- 9019556
TI  - [Single dose toxicity studies of metabolite, degradation product and impurity of
      montirelin hydrate (NS-3) in mice].
AB  - Montirelin hydrate (NS-3) is a new drug for the treatment of disturbance of
      consciousness. The single dose toxicity studies of its degradation product and
      impurity (CNK-603) and its metabolite (CNK-6004) were conducted in Slc: ddY mice.
      The compounds were administered intravenously to male and female mice. Deaths
      occurred in both sexes of mice receiving more than 125 mg/kg of CNK-603. There
      were no treatment-related effects on survival in both sexes of mice receiving
      doses up to 2,000 mg/kg of CNK-6004. Approximate lethal dose of CNK-603 was 125
      mg/kg and lethal dose of CNK-6004 was more than 2,000 mg/kg. Decrease in
      locomotor activity was observed in mice receiving the two compounds. Tremor,
      prone position and dyspnea were seen in mice receiving CNK-603. The body weight
      showed no changes attributable to the dosing of the two compounds in mice. In
      autopsies, congestion and hemorrhage in the lung were observed in dead mice given
      CNK-603. There were no remarkable changes in mice given CNK-6004. These results
      show that the lethal dose of CNK-603 is over 4 times lower than that of
      montirelin hydrate, and that CNK-6004 is less toxic than montirelin hydrate.

PMID- 9019557
TI  - [Five-week intravenous toxicity study of montirelin hydrate (NS-3) in rats
      followed by 4-week recovery test].
AB  - A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the
      treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats.
      Male and female rats were given the drug intravenously for 5 weeks at doses of 0
      (control), 0.05, 0.5, 5 and 50 mg/kg. After discontinuation of the treatment, a 4
      week recovery test was also conducted in the 0, 0.5 and 50 mg/kg groups. No
      deaths related to the treatment were observed. Tremor was seen in the 50 mg/kg
      group. Polyuria was observed in the 5 and 50 mg/kg groups. There were decreases
      in body weight gain in the 0.5 mg/kg group and over of males, and in food
      consumption in all male dose groups and increase in water consumption in the 5
      and 50 mg/kg groups. In blood chemical examination, decrease in triglyceride was
      observed in the 5 and 50 mg/kg groups of males. Urinalysis showed increase in
      urine volume in the 0.5 mg/kg group and over. Ophthalmoscopic and hematologic
      examinations failed to show any abnormalities attributable to the treatment.
      Pathological examination disclosed serous cell hypertrophy of the submandibular
      gland in all dose groups and increase in its organ weight in the 0.5 mg/kg group
      and over. The changes mentioned above were satisfactorily reversible except for
      the serous cell hypertrophy of the submandibular gland in the 50 mg/kg group. The
      decrease in food consumption and serous cell hypertrophy of the submandibular
      gland in the 0.05 mg/kg group were considered to be of no toxicological
      significance. These results show that the NOAEL of montirelin hydrate is 0.05
      mg/kg for 5-week repeated dose toxicity in rats.

PMID- 9019558
TI  - [Twenty-six-week intravenous toxicity study of montirelin hydrate (NS-3) in rats
      followed by 9-week recovery test].
AB  - A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the
      treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats.
      Male and female rats were given the drug intravenously for 26 weeks at doses of 0
      (control), 0.0004, 0.02, 1 and 50 mg/kg. After discontinuation of the treatment,
      a 9-week recovery test was also conducted in the 0, 1 and 50 mg/kg groups. No
      deaths related to the treatment were observed. Tremor and polyuria were seen in
      the 50 mg/kg group. There were decrease in body weight gain, and increase in
      water consumption in the 1 and 50 mg/kg groups. In those dose groups of males,
      decrease in food consumption was observed. Ophthalmoscopic examination failed to
      show any abnormalities attributable to the treatment. Blood chemical examination
      disclosed decrease in total cholesterol in the 50 mg/kg group. There were also
      decreases in phospholipid in the 50 mg/kg group of females, and in triglyceride
      in the 1 and 50 mg/kg groups of males. Urinalysis and hematologic examination
      failed to show any abnormalities attributable to the treatment. In pathological
      examination, serous cell hypertrophy and increase in organ weight of the
      submandibular gland were observed in the 1 and 50 mg/kg groups, and increase in
      organ weight of thyroid was revealed in the 0.02 mg/kg group and over. The
      changes mentioned above were satisfactorily reversible except for the decrease in
      food consumption in the 50 mg/kg group of males. Increased thyroid weight in the
      0.02 mg/kg group was considered to be of no toxicological significance. These
      results show that the NOAEL of montirelin hydrate is 0.02 mg/kg for 26-week
      repeated dose toxicity in rats.

PMID- 9019559
TI  - [Four-week intravenous toxicity study of montirelin hydrate (NS-3) in dogs
      followed by 4-week recovery test].
AB  - A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the
      treatment of disturbance of consciousness, was conducted in beagle dogs. The dogs
      were given the drug intravenously for 4 weeks at doses of 0 (control), 0.0002,
      0.002, 0.02, 0.2, 2 and 20 mg/kg in males and 0, 0.2, 2 and 20 mg/kg in females.
      After discontinuation of the treatment, a 4-week recovery test was also conducted
      in the 0 and 20 mg/kg groups. No deaths related to the treatment were observed.
      There were no changes in body weight gain, and food and water consumptions. Nasal
      discharge was seen in all dose groups. Salivation, emesis and hypoactivity were
      observed in the 0.2 mg/kg group and over. Licking chops were seen in the 2 and 20
      mg/kg groups. Trembling and agitated/restless behavior were seen in the 20 mg/kg
      group. Electrocardiographic examination revealed elevated heart rate in the 0.2
      mg/kg group and over. Ophthalmoscopic and hematologic examinations, and
      urinalysis failed to show any abnormalities attributable to the treatment. Blood
      chemical examination disclosed increases in T3 level in the 2 and 20 mg/kg groups
      of males and in T4 level in the 0.2 mg/kg group and over of males. There were no
      pathological findings attributable to the treatment. The changes mentioned above
      were satisfactorily reversible. The nasal discharge seen in the 0.02 mg/kg group
      and below was considered to be of no toxicological significance. These results
      show that the NOAEL of montirelin hydrate is 0.02 mg/kg for 4-week repeated dose
      toxicity in dogs.

PMID- 9019560
TI  - [Twenty-six-week intravenous toxicity study of montirelin hydrate (NS-3) in dogs
      followed by 9-week recovery test].
AB  - A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the
      treatment of disturbance of consciousness, was conducted in beagle dogs. Male and
      female dogs were given the drug intravenously for 26 weeks at doses of 0
      (control), 0.02, 0.2, 2 and 20 mg/kg. After discontinuation of the treatment, a 9
      week recovery test was also conducted. No deaths related to the treatment were
      observed. Nasal discharge in all dose groups, and tremor, salivation and emesis
      in the 0.2 mg/kg group and over were seen. Decrease in body weight gain was
      observed in the 2 and 20 mg/kg groups. There were no abnormalities in body
      temperature, and food and water consumptions. Urinalysis and
      electrocardiographic, ophthalmoscopic and hematologic examinations failed to show
      any abnormalities attributable to the treatment. In blood chemical examination,
      increase in T3 level was observed in the 2 and 20 mg/kg groups of females. There
      were no pathological findings attributable to the treatment. The changes
      mentioned above were satisfactorily reversible. The nasal discharge seen in the
      0.02 mg/kg group was considered to be of no toxicological significance. These
      results show that the NOAEL of montirelin hydrate is 0.02 mg/kg for 26-week
      repeated dose toxicity in dogs.

PMID- 9019561
TI  - [Reproductive and developmental toxicity studies of montirelin hydrate (1)-
      Fertility study in rats by intravenous administration].
AB  - A study of fertility and early embryonic development to implantation of
      montirelin hydrate (NS-3), a new drug for the treatment of disturbance of
      consciousness, was conducted in Sprague-Dawley rats. Male rats were given the
      drug intravenously from 63 days before mating to the end of mating period and
      female rats from 14 days before mating to day 7 of pregnancy; the dose levels for
      both males and females were 0 (control), 0.02, 1 and 50 mg/kg. The females were
      sacrificed on day 20 of pregnancy for examination of their fetuses. In the 50
      mg/kg group, tremor, disappeared within some minutes, was observed during
      administration period in all animals. Food and water consumptions increased in
      the females and body weight gain was suppressed in the males. Moreover prolonged
      estrus cycle was observed at early period of the administration in the females,
      but it recovered at late period of the administration. However, there were no
      toxicities in the males and females in the 1 mg/kg or less groups. The drug had
      no adverse effects on reproductive function of the parent animals, or on
      development of fetuses. These results show that the NOAEL of montirelin hydrate
      are 1 mg/kg for general toxicity in parent animals, and 50 mg/kg for reproductive
      function of the parent animals and for development of fetuses.

PMID- 9019562
TI  - [Reproductive and developmental toxicity studies of montirelin hydrate (2)-
      Teratogenicity and postnatal study in rats by intravenous administration].
AB  - A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment
      of disturbance of consciousness, during the period of organogenesis was conducted
      in Sprague-Dawley rats. Female rats were given the drug intravenously at dose
      levels of 0 (control), 0.02, 1 and 50 mg/kg from day 7 to day 17 of pregnancy.
      Twenty-three or twenty-five female rats per dose level were sacrificed on day 20
      of pregnancy for examination of their fetuses, and the pregnant rats (13-15 per
      dose levels) were allowed to deliver naturally for postnatal examination of their
      offspring. In the 1 or 50 mg/kg group, water consumption and the weights of
      adrenals of the dams increased and the weights of the thymus of the dams
      decreased. In addition, tremor, disappeared within some minutes, was observed
      from day 7 to day 16 of pregnancy in all dams given 50 mg/kg. Moreover, food
      consumption increased and the weights of the submaxillary glands of the dams
      given 50 mg/kg increased. The drug had no effect on the number of corpora lutea
      and implantations, on fetal mortality, on fetal body weights, on sex ratio, or on
      external, visceral and skeletal development of the fetuses. The drug also did not
      affect delivery. The drug did not have any adverse effects on the newborn such as
      the number of live newborns, birth index and body weights of live newborn, or on
      the postnatal development of the first generation offspring (F1) such as
      differentiation, functional development, emotionality, motor ability, learning
      ability or reproductive performance. The drug also had no adverse effects of the
      second generation offspring (F2). These results show that the NOAEL of montirelin
      hydrate are 0.02 mg/kg for general toxicity in mother animals, 50 mg/kg for
      pregnancy and delivery of mother animals and 50 mg/kg for development of their
      offspring.

PMID- 9019563
TI  - [Reproductive and developmental toxicity studies of montirelin hydrate (3)-
      Teratogenicity study in rabbits by intravenous administration].
AB  - A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment
      of disturbance of consciousness, during the period of organogenesis was conducted
      in New Zealand white rabbits. Female rabbits were given the drug intravenously at
      dose levels of 0 (control), 0.01, 0.1 and 1 mg/kg from day 6 to day 18 of
      pregnancy. Female rabbits were sacrificed on day 29 of pregnancy for examination
      of their fetuses. In the 0.1 mg/kg group, food consumption decreased slightly. In
      the 1 mg/kg group, tachypnea, salivation and rhinorrhea were observed, and body
      weight and food consumption decreased and water consumption increased. The drug
      had no effect on the number of corpora lutea and implantations, or on fetal
      mortality, on fetal body weights, on placental weight, on sex ratio, or on
      external, visceral and skeletal development of the fetuses. These results show
      that the NOAEL of montirelin hydrate are 0.1 mg/kg for general toxicity in mother
      animals, and 1 mg/kg for pregnancy of mother animals and for development of
      fetuses.

PMID- 9019564
TI  - [Reproductive and developmental toxicity studies of montirelin hydrate (4)-
      Perinatal and postnatal study in rats by intravenous administration].
AB  - A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment
      of disturbance of consciousness, during the perinatal and lactation periods was
      conducted in Sprague-Dawley rats. Female rats were given the drug intravenously
      at dose levels of 0 (control), 0.02, 1 and 50 mg/kg from day 17 of pregnancy to
      day 21 after delivery. All pregnant rats were allowed to deliver naturally for
      postnatal examination of their offspring. In the 1 and 50 mg/kg groups, food and
      water consumptions decreased after delivery and the weights of adrenals of the
      dams increased. In addition, tremor, disappeared within some minutes, was
      observed during administration period in all dams given 50 mg/kg. Moreover, body
      weight gain was suppressed after delivery, and the weights of submaxillary glands
      increased, and the weights of thymus and liver decreased in the dams given 50
      mg/kg. The drug did not affect delivery. The drug did not have any adverse
      effects on the newborn including the number of live newborns, birth index and
      body weights of live newborn. In the 1 or 50 mg/kg group, body weight gains were
      suppressed and food consumption decreased in the offspring. The drug did not have
      any adverse effects on the postnatal development of the offspring such as
      differentiation, functional development, emotionality, motor ability, learning
      ability or reproductive performance. These results show that the NOAEL of
      montirelin hydrate are 0.02 mg/kg for general toxicity in mother animals, 50
      mg/kg for reproductive function in mother animals and 0.02 mg/kg for their
      offspring.

PMID- 9019566
TI  - [Vascular irritability study of montirelin hydrate (NS-3) injection in rabbits].
AB  - A vascular irritability study of montirelin hydrate (NS-3) injection, a new drug
      for the treatment of disturbance of consciousness, was conducted in Japanese
      white rabbits. The concentration of montirelin hydrate was 4 mg/ml. Saline and
      0.75% acetic acid were used as negative and positive control, respectively. In a
      part of the ear vein, 0.05 ml of each compound was allowed to remain for 3 min
      after intravenous injections once a day for 8 days. Inflammation in peri-venous
      region and thrombus were macroscopically observed in injection sites of rabbits
      with the montirelin hydrate injection group. However, no changes were seen with
      the negative control group. Histopathological examination revealed periphlebitis,
      desquamation of endothelial cells and thrombus in rabbits given montirelin
      hydrate injection or saline. But incidence and degree of periphlebitis caused by
      montirelin hydrate injection were higher than those caused by saline. On the
      other hand, the irritating changes caused by 0.75% acetic acid were severer than
      those by montirelin hydrate injection. These results show that montirelin hydrate
      injection has a very weak vascular irritability in the ear of rabbits.

PMID- 9019565
TI  - [Mutagenicity studies of montirelin hydrate (NS-3)].
AB  - Montirelin hydrate (NS-3), a new drug for the treatment of disturbance of
      consciousness, was examined for mutagenicity in the reverse mutation test, the
      chromosome aberration test in vitro, and the micronucleus test in mice. The
      reverse mutation test was performed at dose range of 156.25-5,000
      micrograms/plate using Salmonella typhimurium strains, TA1535, TA100, TA1537, and
      TA98, and Escherichia coli WP2uvrA. The drug did not increase revertant colonies
      significantly in any of the test strains with or without metabolic activation
      system (S-9mix). The chromosome aberration test was carried out at dose range of
      300-4,800 micrograms/ml using cultured Chinese hamster lung cells (CHL/IU). No
      significant increases of the frequencies of cells with chromosomal aberrations
      were observed with or without metabolic activations. The micronucleus test was
      conducted in the bone marrow cells of Slc:ddY male mice. Mice were given the drug
      by a single intraperitoneal administration at doses of 0, 250, 500, 1,000, and
      2,000 mg/kg. There were no significant increases in the frequencies of
      micronucleated polychromatic erythrocytes at any dose levels. These results show
      that montirelin hydrate has no mutagenic activity in vitro or in vivo.

PMID- 9019567
TI  - [Antigenicity study on montirelin hydrate (NS-3)].
AB  - An antigenicity study of montirelin hydrate (NS-3), a new drug for the treatment
      of disturbance of consciousness, was conducted in Hartley guinea pigs. Animals
      were sensitized twice by subcutaneous injections of montirelin hydrate in
      combination with Freund's complete adjuvant and twice by intramuscular injections
      of montirelin hydrate alone. Montirelin hydrate was found to be negative in the
      homologous passive cutaneous anaphylaxis test carried out with sera from the
      sensitized guinea pigs. Negative results were also obtained in the active
      cutaneous anaphylaxis test and the active systemic anaphylaxis test in guinea
      pigs sensitized with montilerin hydrate. These results show that montirelin
      hydrate has no antigenicity under the present experimental conditions.

PMID- 9019568
TI  - [Dislocation of lens particles during cataract surgery].
AB  - BACKGROUND: The charts of 46 patients with dislocated lens particles during
      cataract surgery were reviewed. Forty patients had trans-pars plana vitrectomy; 5
      were treated medically and one had retinal detachment repair only. MATERIAL AND
      METHODS: The following complications were associated with dislocated lens
      particles: uveitis 87%, glaucoma 66%, corneal edema 71%, retinal detachment 5%.
      RESULTS: The vision on the initial visit was 20/200 or worse in 85%. After
      vitrectomy the final vision was 20/40 or better in 58%. Visual acuity of 20/40 or
      better was obtained in 72% of patients who had surgery the same day; in 55% who
      had surgery later and in 64% with initial IOL placement. Insertion of an
      intraocular lens at the time of cataract surgery is not contraindicated.
      CONCLUSION: The best visual acuity occurred in patients who had vitrectomy the
      same day as cataract surgery. Small lens particles may be left in the eye. Trans
      pars plana vitrectomy is a successful method of treatment of dislocated lens
      particles during cataract surgery.

PMID- 9019569
TI  - [Vitrectomy in ocular complications of diabetes. I. Early and late results of
      vitrectomy].
AB  - Results of 168 pars plana vitrectomies (ppV) of 144 diabetics are presented. In
      26.2% of eyes before surgery, vitreous hemorrhage without detachment of the
      retina was present. In the remaining eyes, different stages of tractional
      detachment occurred. Visual acuity worse than 1/50 was observed in 83.9% of eyes
      before surgery. Results of ppV were evaluated on the 7th day and after the 3rd,
      6th, 12th and 18th month following the procedure. Anatomical and functional
      success was achieved in about 80% and 67% of treated eyes, respectively, over the
      whole follow-up period.

PMID- 9019570
TI  - [Early diagnosis of optic nerve neuropathy in multiple sclerosis].
AB  - PURPOSE: To evaluate diagnostic sensitivity of clinical tests in optic
      demyelinating neuropathy. MATERIAL AND METHODS: We examined 21 persons (38 eyes)
      with confirmed sclerosis multiplex (SM) with no episodes of posterior optic
      neuritis in the history of the disease. The examination method included: Static
      perimetry of central visual field (30 degrees, by Octopus 101), pattern visual
      evoked potentials (p VEP), colour photographs of optic disc and magnetic
      resonance imaging (MR) of central nervous system, optic nerves and optic chiasm.
      Visual acuity and colour vision were normal. RESULTS: There was statistically
      significant elongation in the latency of P 100 in pattern VEP (> 118 ms, 3 x SD),
      and significant reduction in mean light sensitivity (MS) in central visual field.
      MRI revealed demyelinisation in cortex and/or spinal cord of all patients and
      demyelinating lesion in optic nerve of one patient. There was no Gd-DTPA
      enhancement. In statistical analysis there was no correlation between results of
      pattern VEP, IMR, morphology of optic disc, and duration of SM, stage of the
      disease (in Kurtzke gradation scale) or age of patient. In regression analysis
      there were statistically significant relationships (p < 0.05) between results of
      central static perimetry, duration and stage of disease.

PMID- 9019571
TI  - [Central visual field in patients with multiple sclerosis without symptoms of
      optic neuritis].
AB  - PURPOSE: To estimate central visual field (30 degrees) of patients suffering from
      multiple sclerosis (SM). SM was confirmed by magnetic resonance imaging. MATERIAL
      AND METHODS: There was no posterior optic neuritis in the history of the disease.
      The visual acuity of examined the 28 eyes was 1,0. The results of static
      perimetry were analysed by regression analysis. RESULTS: There were significant
      relationships between mean sensitivity (MS) and duration of the disease, stage of
      the disease (in Kurtzke gradation scale) and age. Mean defect (MD) was
      significantly higher in the upper half of central visual field and between 15-30
      degrees (p < 0.05). We observed positive relationships between MD, short time
      fluctuation (STF) and corrected loss variance (CLV). We found negative
      correlations between MS, MD, CLV and STF. Mean reliability factor RF was < 10%.
      CONCLUSION: Static perimetry seems to be a useful test in early diagnosis and
      monitoring of optic nerve neuropathy in SM.

PMID- 9019572
TI  - [Use of cryotherapy in retinopathy of prematurity].
AB  - PURPOSE: To present our experiences in cryotherapy for ROP. MATERIAL AND METHODS:
      From October 1991 to August 1995, transscleral cryotherapy was applied in 128
      eyes of 70 babies with ROP. There were 34 girls and 36 boys with birth weight
      between 650 g and 1990 g and gestational age from 24 to 36 weeks. In above 90% of
      cases, ROP reached zone II and stage 3 with "plus" disease. In 84% of the eyes
      the extent of ROP was greater than 5 clock hours. Prethreshold severity was
      diagnosed in 7 and threshold in 110 eyes. In 11 eyes these categories could not
      be seventy determined. The chronologic age of infants at cryotherapy ranged from
      8 to 22 weeks, mean 12 weeks. In all cases, cryotherapy was carried out under
      general anesthesia using a technique described in CRYO-ROP study. No serious
      complications during or after cryotherapy were observed. RESULTS: Favorable
      structural outcome was found in 119 eyes of 70 treated infants. In 82 eyes of 46
      infants, with at least 12-month follow-up examination, also functional outcome
      was evaluated, basing on the examination with the Teller Acuity Card Procedure;
      the results were favorable in 57% of the eyes. Structural and functional outcomes
      were in agreement in 47 of the 82 eyes and discordant in 33. CONCLUSIONS: Our
      experience confirms the benefit of cryotherapy in the treatment of active ROP. In
      most cases cryotherapy should be applied in threshold ROP but in some cases
      especially in those with very rapid progression it should be done earlier.
      Because of the unpredictability of the natural course of ROP it is essential to
      use the scheme of ophthalmological examinations proposed by CRYO-ROP Study.

PMID- 9019573
TI  - [Use of contact lenses in children with severe myopia].
AB  - PURPOSE: To present own observation on the usefulness of soft contact lenses in
      treatment of high myopia in children and youth. MATERIAL AND METHODS: 43 children
      with high myopia were selected from 2320 patients fitted with lenses due to
      refraction errors. The whole complex of ophthalmological examinations including
      ultra sound scan of eyeballs and measurement of corneal sensitivity were
      performed prior to the lens fitting. Visual acuity and stereoscopy of glass and
      contact lenses were estimated. RESULTS: The contact lens fitting enabled to
      achieve significant visual acuity improvement in all patients. The improvement
      was observed in 53.4% patients in comparison with glass correction. Stereoscopy
      was achieved in 58.1% patients, with glass correction and 81.4% patients with
      contact lenses. CONCLUSIONS: Soft contact lenses are very useful in high myopia
      correction in growing-up patients. The basic and indispensable factor of
      successful contact lens fitting is a good cooperation with parents.

PMID- 9019574
TI  - [Clinical evaluation of Spersallerg preparation for non-infectious conjunctivitis
      and infectious conjunctivitis with a hyperergic component].
AB  - PURPOSE: To estimate the efficacy of "Spersallerg" eye drops from "CIBA-Vision"
      in conjunctivitis without any acute exogenic infection. MATERIAL AND METHODS: The
      material consisted of 47 eyes, including 14 eyes with papillary conjunctivitis, 4
      eyes with vermal conjunctivitis, 1 eye with giant papillary inflammation caused
      by wearing contact lens, 8 eyes with blepharitis and conjunctival allergic
      component, 6 eyes with allergy on cosmetics, 4 eyes with allergy on local
      anaesthetics and 10 eyes with postoperative, non-allergic conjunctival
      irritation. The method of evaluation was based on individual patient's opinion on
      his subjective symptoms and on slit-lamp examination of conjunctival, palpebral
      and corneal sings, typical for this type of inflammation. RESULTS AND
      CONCLUSIONS: The results showed that "Spersallerg" is clinically useful in most
      of allergic conjunctivitis cases, and in other inflammations with hyperergic
      component. It proved to be efficient as the support for causal treatment
      minimizing subjective and objective signs of the disease.

PMID- 9019575
TI  - [Evaluation of the usefulness of the laryngeal mask for general anesthesia in eye
      microsurgery--preliminary results].
AB  - PURPOSE: This prospective study was designed to compare intraocular pressure
      changes and haemodynamic response to insertion of either a laryngeal mask or an
      orotracheal tube during general anaesthesia for cataract surgery. MATERIAL AND
      METHODS: The effect of techniques (tracheal tube-TT, laryngeal mask airway-LMA)
      securing a clear upper airway on the heart rate changes (HR), arterial pressure
      (SAP, DAP), oxygen saturation (SpO2), end-tidal carbon-dioxide pressure (Et-CO2),
      intraocular pressure (IOP) and the incidence of coughing, stridor and sore throat
      was analysed in 60 patients undergoing cataract surgery during general
      anaesthesia. RESULTS: The mean values for HR, SAP, DAP and IOP measured before
      and after induction of anaesthesia were not different in both groups. After
      securing a clear airway, mean HR increased in TT group to 95.5/min and decreased
      to 75.7/min in LMA group. SAP increased in TT group to 131 mmHg, DAP to 82.6
      mmHg, whilst in LMA group both values decreased to 98.6 mmHG and 66.3 mmHg,
      respectively. The significant difference in IOP values was observed after
      intubation or using laryngeal mask. In TT group, intraocular pressure increased
      to 15 mmHg in healthy eye and to 13.6 mmHg in ill eye whilst there was a decrease
      in LMA group to 5.5 and 7.43 mmHg, respectively. Furthermore, a greater incidence
      of such complications as coughing, stridor and sore throat in TT group was
      observed. CONCLUSION: The results show that using LMA in microsurgery during
      general anaesthesia is more advantageous and safer for patients in comparison
      with tracheal intubation.

PMID- 9019576
TI  - [Axial and para-axial fluorophotometry in optic neuropathies].
AB  - PURPOSE: To investigate optic neuropathies, with normal results in fluorescein
      fundus angiography, by axial and paraaxial fluorophotometry (a type of
      topographic vitreous fluorophotometry) in order to determine differences examined
      in the amount of fluorescein leakage in macular and optic disc. MATERIAL AND
      METHODS: We studied 12 eyes with unilateral idiopathic retrobulbar inflammatory
      optic neuropathy and 4 eyes with unilateral posterior ischaemic optic neuropathy
      during the acute phase: control group consisted of 5 healthy eyes. After 3-4
      months, in final stage of optic neuropathies, in which primary atrophy of optic
      disc developed (6 eyes), fluorophotometric examinations were repeated. All cases
      of control group underwent axial and paraaxial fluorophotometry. Complete
      ophthalmic, physical and neurological examinations were performed. RESULTS: The
      mean fluorophotometric values of PVPR (posterior vitreous penetratio-ratio) for f
      scans (foveal) were lower than for t-scans (PVPRf < PVPRt) in all neuropathies
      during the acute phase but all values of PVPR were higher than in control eyes.
      In late phase of the neuropathies in which primary atrophy of optic disc
      developed we found a trend: PVPRt < PVPRf, but all values of PVPR were lower than
      in control eyes. We noticed increased permeability of the blood-ocular barrier
      and difference between fluorophotometric readings for optic disc directions (t
      paraaxial scans) and for foveal directions (f-axial scans) in optic neuropathies
      during the acute phase, when the findings on ophthalmoscopic and fluorescein
      fundus angiography were normal.

PMID- 9019577
TI  - [Carotid-cavernous fistula--diagnostic possibilities of color doppler
      ultrasonography].
AB  - PURPOSE: The diagnosis of carotid-cavernous fistula as a cause of exophthalmus,
      especially in cases of minor shunts, can be difficult. Angiography is the basic
      examination of choice is angiography. The aim of the work was to assess the
      usefulness of colour-coded Doppler ultrasonography (CD-US) in diagnosis of
      fistulas. MATERIALS AND METHODS: CD-US examinations were analysed in four
      patients with carotid-cavernous shunts (two post-traumatic, two spontaneous). The
      diagnosis was confirmed by angiography and computer tomography (CT). RESULTS:
      Characteristic ultrasonographic appearance in all four cases of fistula was
      noted. Relation between dynamics of the lesion in CD-US and size of the shunt in
      CT was found. CONCLUSIONS: CD-US can be recommended both in the initial diagnosis
      of carotid-cavernous fistulas as well as in follow-up of the treatment.

PMID- 9019578
TI  - [Clinical examinations in Usher's syndrome].
AB  - In this paper we are showing the results of clinical examinations in the family
      in which three siblings had the following symptoms: congenital deafness and
      nyctalopia. Clinical examinations including genetic counseling, audiometry,
      caloric test, Flash ERG, perimetry, computer tomography revealed total deafness,
      no vestibular function, and an advanced stage of retinitis pigmentosa. On the
      basis of clinical results, we determined the correct diagnosis: autosomal
      recessive Usher's syndrome-type 1. Diagnosis of the syndrome enables
      qualification of prognosis, complications, possibility of treatment and the risk
      of having the disease in the next generations. Early identification of the
      presence of Usher's syndrome can help in the formulation of an appropriate
      educational and training program. It seems purposeful that all patients with
      hearing loss should be examined by ophthalmologists.

PMID- 9019579
TI  - [Ocular complications in toadstool mushroom poisoning].
AB  - We present a case of a young man poisoned with Amanita phalloides. He survived
      thanks to intensive treatment, however he had multiple complications, including
      endophthalmitis in one eye, which was enucleated, and macular deposits in the
      second eye, which was affected by glaucoma.

PMID- 9019580
TI  - [Modern treatment of malignant intraocular melanomas].

PMID- 9019581
TI  - Encirclement of the globe and air in the vitreal cavity--unconsidered aspects.

PMID- 9019582
TI  - [Outline of the history of the Medical Sciences and Ophthalmology University in
      Wroclaw].

PMID- 9019583
TI  - [Electrophysiologic tests for diagnosis of congenital night blindness].
AB  - Electrophysiological study in diagnosis of congenital stationary night blindness.
      MATERIAL AND METHODS: The goal of this study was to describe a family with X
      linked congenital stationary night blindness (CSNB) in which 3 brothers had
      similar symptoms: night blindness, reduced visual acuity and "negative" type of
      Flash ERG. RESULTS: Electrophysiological study permitted to differentiate CSNB
      from generalized progressive retinal degeneration, what has a prognostic value
      for these patients.

PMID- 9019584
TI  - [Treatment of infantile strabismus with eye movement disorders].
AB  - PURPOSE: Possibilities of application of localization method in the treatment of
      infantile strabismus in a very early period are presented. MATERIAL AND METHODS:
      The authors applied treatment with hypercorrective and compensating prisms in 17
      children with infantile strabismus. The age of the children ranged from 0.5 to 5
      years, mean age-1 year. All children were found to have no motility or limited
      motility of eyes toward the temples. Initially, the children's eyes were
      alternately occluded in prisms whose strength prevalently was 30-40 pr dptr
      before each eye, with base toward the temple. After 1-3 months motility of the
      eyes appeared. Next, glasses compensating the squint angle were worn, without
      covering the eyes, starting with 1/2 hour 3 times a day and gradually prolonging
      the wearing time. Hypercorrective prisms were further used with alternate
      occlusion of the eyes. RESULTS: In all children partial or complete correction of
      motility was achieved. Further treatment of strabismus followed the rules of the
      localization method.

PMID- 9019585
TI  - [Diplopia as a complication after surgery for strabismus in adolescents and
      adults].
AB  - Diplopia may occur following surgery for the correction of constant manifest
      strabismus. Young children rarely complain of diplopia because of the plasticity
      of their visual system and the rapid development of suppression. However, in
      older children and adults post-operative diplopia may occur either as a transient
      well-tolerated phenomenon or occasionally as an intractable problem. It is a
      standard practice to carry out tests prior to surgery to try and predict the risk
      of post-operative diplopia, although the value of these tests and the incidence
      and severity of diplopia following squint surgery is not well documented. We
      reviewed the records of these 22 out of all our patients operated for squint who
      had diplopia (aged 13-45). 13 subjects presented diplopia only for 1 or 2 days
      after surgery 8 had intermittent one with good tolerance and 1 acquired constant
      diplopia (she was operated). Pre- and post-operative agents which could have had
      an impact on diplopia occurrence were evaluated. Diplopia was found in 48%
      patients who had positive test predicting the risk of post-operative diplopia.
      The test thus seems to be quite limited in its reliability and prior to surgery
      the patients should be thoroughly informed about a possibility of diplopia
      occurring as a surgery complication.

PMID- 9019586
TI  - [Conservative treatment of vertical recti and oblique muscle deviation in
      permanent and accommodative strabismus].
AB  - The aim of this study was observation of influence of exercises with
      hypercorrective prisms on the behavior of vertical recti and oblique muscles. The
      study covered 182 persons with permanent strabismus (4 persons were operated
      early) and 8 children with accommodative strabismus. As treatment we applied
      exercises with hypercorrective prisms of 35 dioptres in front of each eye with
      the edge in direction of the biggest deviation of the eye. A full regression of
      the hyperfunction of muscles was noticed in 25 patients. The favourable changes
      were achieved in 38 patients. However the majority of patients were not doing the
      exercises systematically. Surely it is not the only reason of the lack of final
      beneficial result of exercises. The applied localization exercises with prismatic
      hypercorrection in hyperfunctions of vertical recti and oblique muscles gave
      beneficial result in form of regression of these hyperfunctions or reduction of
      the range of their deviation. There was also favorable influence on the
      regression of "residual" deviations of eye after operations. Application of such
      exercises in accommodative strabismus with hyperfunction of vertical recti and
      oblique muscles prevent from dissociation of binocular vision and genesis of
      permanent strabismus.

PMID- 9019587
TI  - [The effect of treatment with prisms on head position in persons with nystagmus-
      preliminary report].
AB  - The aim of the work is to inspect the influence of the treatment by using hyper
      correcting prisms on the vertical deviations of the eyes and on the head's
      position in persons with nystagmus. We observed 4 persons with nystagmus without
      strabismus and 3 persons with convergent squint. In persons without strabismus
      the prismatic correction placed with an edge in the direction of the "calm's
      zone" (quiet's zone) to obtain the straight position of the head when looking
      forwards was applied. Twice a day during 10 minutes the patients were making the
      movement's exercises in the vertical and horizontal direction looking by the
      prism separately by each eye. This prism (often 35 D prism) was placed with the
      edge in the direction of greater deviation of the oblique inferior muscles and
      the left rectus inferior muscle. Patients with convergent strabismus were treated
      according to the principles of localization method with consideration of the
      localize exercises by using hyper-correcting prisms in the vertical and
      horizontal directions. Two patients had a surgery in order to eliminate not
      aesthetic and strong prisms which were applied because of large horizontal
      squint. One patient with convergent alternate squint with hyperactivity of both
      inferior oblique muscles and inferior rectus muscle of the left eye was treated
      without surgery, only by the conservative treatment with prisms. In all patients
      we obtained a straight position of the head despite of the nystagmus still
      existing during the eyes movements in some directions. The treatment by using
      hyper-correcting prisms can completely replace the surgical treatment or is able
      to supplement it and prevent relapses.

PMID- 9019588
TI  - [Visual manual localization in the horizontal plane in persons with vertical
      deviations of the eyes].
AB  - PURPOSE: To check the behavior of the visual manual localization (v.m.l.) in the
      horizontal plane which can represent the state of the cortical connections
      between visual occipital centers and motor centers for the hand movement.
      MATERIAL AND METHODS: The examinations were performed using the manual localizer.
      The authors examined 14 patients with vertical deviations of the eyes caused by
      hyperfunction of the oblique inferior muscles and rectus inferior muscle in the
      left eye. V.m.l. examined both without the test and with the provoking test were
      in the range of the physiological norm which excludes the organic changes in the
      central nervous system. RESULTS: The authors suggest that the reason of the
      vertical deviations of the eyes is not localized in the higher parts of the
      nervous system but probably depends on unequal development of the connections in
      the nuclei of the oculomotor nerves.

PMID- 9019589
TI  - [Tissue plasminogen activator (t-PA) in aqueous humor of patients with cataract].
AB  - PURPOSE: The purpose of the examination was evaluation of tissue plasminogen
      activator (t-PA) concentration and plasminogen activator inhibitor (PAI) activity
      in aqueous humor of the eye and plasma of blood in patients operated on cataract.
      MATERIAL AND METHODS: In aqueous humor and citrate plasma of 24 patients
      undergoing cataract surgery the concentration of t-PA (Imulyse Biopool) and the
      activity of PAI-1 (Spectrolyse Biopool) were determined. RESULTS: In aqueous
      humor of 90% patients the concentration of t-PA-Ag in mean value 1.5 +/- 2.7
      ng/ml was ca 20% of the level present in plasma. In aqueous humor of nearly all
      patients no PAI-1 activity could be detected. In a little group of persons
      because of small amounts of aqueous humor, other fibrinolytic parameters were
      also estimated and the presence of urokinase-type plasminogen activator (u-PA),
      alfa-2 antiplasmin (alfa-2AP) and plasmin-alfa-2 antiplasmin (PAP) complexes but
      no activity of protein C were observed. CONCLUSION: The presence of PAP complexes
      in aqueous humor indicates on intensive plasminogenesis in vivo. Our examinations
      confirm the role of fibrinolytic process in physiological and pathological
      processes occurring in the eye.

PMID- 9019590
TI  - [Post-mortem concentration of tissue plasminogen activator (t-PA) and plasminogen
      activator inhibitor (PAI-1) in the vitreous body of the human eye].
AB  - After sudden death the blood remains fluid and after late death the thrombi are
      present in heart and vasa. Earlier we observed after sudden death high
      concentrations of t-PA Ag in plasma with strong activation of fibrinolysis,
      consumption of PAI-1, plasminogen, fibrinogen, alfa-2 antiplasmin and a big
      increase of FDP. Fibrinolysis is mainly regulated by t-PA, u-PA and PAI-1.
      PURPOSE: The aim of our study was the evaluation of t-PA and PAI-1 in corpus
      vitreous and plasma of patients after sudden (26) and late death (12). MATERIAL
      AND METHODS: The concentration of t-PA Ag was measured with COA SET of Kabi
      Vitrum and the activity of PAI-1 with reagents of Biopool. RESULTS: In corpus
      vitreous the concentration of t-PA after sudden death was 3.65 +/- 1.83 ng/ml and
      after late death 1.93 +/- 1.63 ng/ml. The activity of PAI-1 was respectively 0.61
      +/- 1.2 IU/ml and 2.25 +/- 3.30 IU/ml. After sudden death the concentration of t
      PA was twice higher and PAI-1 three times lower as after late death. CONCLUSION:
      No dependence of t-PA concentration and the time after death could be observed.

PMID- 9019591
TI  - [Immunologic tests in patients with idiopathic uveitis--preliminary reports].
AB  - AIM: This study aimed to evaluate the immune system function in patients with
      uveitis of unknown aetiology. METHODS: The clinical material comprised 19
      patients with endogenous uveitis. In all cases the following immunological tests
      were performed: serum immunoglobulins A, G, M, total IgE, circulating immune
      complexes, complement components C3c and C4-all determined by laser nephelometry;
      antinuclear antibodies assessed with indirect immunofluorescence method using HEp
      2 cell lines; and antineutrophil cytoplasmic antibodies using indirect
      immunofluorescence test. In 4 cases lupus anticoagulant was measured with APTT
      and dRVVT assays. RESULTS: Among our 19 examined patients immunological
      abnormalities were found in 12 cases. Changes in immunoglobulin concentrations
      were found in 8 cases. In 4 patients abnormalities of the complement system were
      observed. Antinuclear antibodies with speckled pattern in indirect
      immunofluorescence were present in 7 cases. CONCLUSION: In a proportion of
      patients with endogenous uveitis mild immunological abnormalities were present,
      suggesting an autoimmune background of the disease. Studies of the immunological
      profile can therefore help in better evaluation of the patients. It remains to be
      determined whether the observed immunological alterations are of any importance
      in the pathogenesis of the studied disease.

PMID- 9019592
TI  - [Chemical analysis of compounds released after damage of the intraocular lens
      with the Nd: YAG laser].
AB  - PURPOSE: To evaluate the amount of releasing chemical compounds after laser Nd:
      YAG damage of PMMA intraocular lenses. MATERIAL AND METHOD: The study was
      undertaken in vitro condition. In two chemical vials filled with aqua humor-like
      solution 7 intraocular lenses in each were installed. One vial was the control
      group. 500 exposures to the laser Nd: YAG were performed focusing the beam on
      intraocular lenses in second vial. The aqua humor-like solution was analysed by
      gas chromatography in period of 1, 5 and 10 weeks. RESULTS: Methylmethacrylate
      was present in vial with damaged intraocular lenses in the first week after laser
      exposition, the other chemical compounds were observed after this period.
      CONCLUSIONS: 1. Laser Nd: YAG provokes depolymerisation of PMMA to
      methylmethacrylate just in time when damaging factor occurs. 2. Methyl alcohol
      and formaldehyde present in a longer time after damage of PMMA are the products
      of methylmethacrylate reactions. 3. The amount of released chemical compounds is
      so small and seems not to have the toxic properties.

PMID- 9019593
TI  - [Periorbital capillary hemangiomas in children--treatment and monitoring of
      treatment].
AB  - PURPOSE: The purpose of the paper is to present the possibility of treatment of
      periorbital capillary hemangiomas in infancy. MATERIALS AND METHODS: Doppler
      colour ultrasonography was used as a method of diagnosis and monitoring of the
      treatment. The material comprised 11 patients aged from 1 month to 3 years. In 6
      cases local corticosteroid injections were applied, in 3 cases surgical treatment
      was performed, out of which 1 additionally received steroid. RESULTS: Results of
      the treatment were satisfactory in all patients. No serious complications were
      observed. CONCLUSIONS: Basing on these cases, the authors confirmed the opinion
      that intralesional corticosteroid injection is the method of choice in the
      treatment of periorbital infantile hemangiomas. The authors indicate the
      usefulness of Doppler colour ultrasonography in diagnosis, demonstrating the
      extent of lesions and monitoring the response to therapy.

PMID- 9019594
TI  - [Vision defects in two age groups of drivers who caused road accidents].
AB  - The aim of the paper is a comparison of sight defects observed in two age groups
      of drivers who caused severe road accidents. The study material comprised 326
      drivers from the district of Lublin who were divided into two groups. The first
      group consisted of drivers of 50 and under 50 years of age while the second one
      comprised drivers over 50 years of age. In the first group sight defects were
      found in 28% of examined subjects and the second in 83.9%. The category of
      driving licence was changed because of detected sight defects in 7% of drivers
      from the first group and in 41% of drivers from the second group. The authors
      point to the necessity of periodical examinations of older drivers and to the
      need for informing drivers about symptoms of aging of the sight organ.

PMID- 9019595
TI  - [Conventional methods in retinal detachment surgery].
AB  - PURPOSE: To evaluate the usefulness of conventional methods in retinal detachment
      (RD) surgery basing on the relationship between factors characterizing clinical
      picture of the RD, the type and course of surgical procedures and the retinal
      reattachment. MATERIALS AND METHODS: 252 patients (252 eyes), operated on in the
      last 5 years in our clinic were enrolled in the studies. There were 120 men and
      132 women, aged 9 to 83, mean 53. In all cases scleral buckling procedures with
      silicone band or sponge and cryocoagulation of the breaks were used. The
      relationship between retinal reattachment and the following parameters were
      examined: visual acuity, retinal degenerations, myopia, extent of the detachment,
      number and kinds of breaks, macular involvement, state of vitreous, PVR,
      intraocular pressure, extent of scleral buckling, subretinal fluid drainage and
      intra- or post-operative complications. RESULTS: Retinal reattachment was
      achieved in 82% of the eyes with one operation and additionally in 7% after
      reoperation. The significant relationship was found between: visual acuity,
      intraocular pressure, extent of the detachment, number of breaks, PVR, extent of
      scleral buckling and retinal reattachment. CONCLUSION: PVR is a significant cause
      of failure in RD surgery with conventional methods and PVR grade C is the
      threshold beyond which the percentage of reattachments decreases to about 50%.
      Value of other risk factors, determining severity of RD is not certain for
      prognosis. Cerclage with silicone band is a method of choice in the majority of
      RD with PVR grade B and C. Our observations do not confirm the reports of severe
      complications caused by cerclage, which might be connected with excessive
      tightening of the band.

PMID- 9019596
TI  - [Surgical decompression of the orbit in a case of post-traumatic retrobulbar
      hematoma].
AB  - The authors present a case of 34-years-old man with retrobulbar hematoma caused
      by blunt injury accompanied by partial palsy of the oculomotor nerve and ischemia
      of the optic nerve and retina. Fractures of the orbit were excluded using
      computer tomography. Surgical decompression of the orbit was performed. The
      authors obtained quick and marked improvement with normal visual acuity and
      limitation of adduction.

PMID- 9019597
TI  - [A case of Leber's idiopathic stellate retinitis and optic neuritis].
AB  - A case of 31-year-old man with Leber's idiopathic stellate retinopathy is
      presented. On the eye fundus there was optic disc swelling and maculopathy with
      yellow star-like foci. The visual acuity was -0,01. Antibiotics and encorton were
      applied in the treatment. During the therapy the visual acuity was improved,
      maculopathy and disc swelling reduced. We wanted to present the above case
      because of its unique occurrence and diagnostic difficulties.

PMID- 9019598
TI  - [Orbitography in orbital fractures].
AB  - The authors present four cases of fractured orbit where the radiological
      examination with contrast orbitography was applied using the new Multiscop
      apparatus with digitized picture from Siemens. The examination was found to be
      very helpful for proper and detailed diagnosis and for choosing the appropriate
      operational method.

PMID- 9019600
TI  - [History of strabismology: I--strabismology in the countries of Western Europe].
AB  - Part I contains a description of treating amblyopia and strabismus since the
      XVIth century. The author deals with the gradual development of ophthalmology
      with regard to the modes of investigations, which automatically influenced the
      evolution of strabology. The description covers the development of German,
      English and French strabology concerning the treatment of binocular vision by
      means of synoptophore, and also the treatment of amblyopia by Bangerter and
      Cuppers's method, as well as penalization. The author discusses the significance
      of evaluating the binolcular vision state by tests in free space, besides the
      synoptophore ones. At the end the author reaches the conclusion that, over such a
      long period of time, there have been trends of resorting to certain methods, e.g.
      Bangerter and Cuppers's, penalization. These methods were gradually discarded by
      many strabologists, and at present time something like a comeback to surgical
      treatment is observed. That recurrence was due to the fact that the conservative
      methods, being improperly used, failed to give any effects at all, or provided
      only temporary improvement. The author emphasizes that the most serious cause
      responsible for the lack of any progress in the world strabology is that the
      cortical processes in the squint are not fully understood and that the causes of
      squint are constantly associated with the extraocular muscles.

PMID- 9019599
TI  - [The role of hemodynamic conditions in the posterior eye segment on genesis and
      development of glaucomatous neuropathy].
AB  - The contemporary literature has widely described the role of insufficiency of
      blood flow in glaucomatous damage. The paper presents the blood supply of the
      optic nerve head and the role of systemic and nocturnal hypotension, vasospasmus
      syndrome, carotide artery disease, location of the wathershed zone in relation to
      the optic disc and the effects of defective autoregulation of blood flow in
      glaucoma. The implications of vascular risk factors in glaucoma for its
      prognostics and management are discussed.

PMID- 9019601
TI  - [History of strabismology: II--strabismology in Poland].
AB  - The author presents an outline of strabology development in Poland since the 50s.
      Original ideas of Polish authors are provided, with three schools of treating
      strabismus existing in this country being discussed. In the final part the author
      highlights the differences between the method used in Szczecin and that in other
      centres implementing previous principles. The lack of consensus among the
      supporters of different methods is attributed to variability in the
      interpretation concerning the inception of mono- and binocular visual sensations,
      both in physiology and squinting subjects. The followers of the Szczecin School
      rely on Starkiewicz's theory which elucidates the genesis of the above-mentioned
      processes on the grounds of the reflex connections that arise between cortical
      centres of vision and all others in cerebral cortex, particularly with centres of
      kinetics and perception. Physicians proceeding with the treatment by old methods
      ascribe in these processes a great role to retinas of both eyes and ocular
      muscles without any explanation with regard to connections involving cerebral
      cortex.

PMID- 9019602
TI  - [Rapid and slow progression of the infection by the type 1 human immunodeficiency
      virus in a population of seropositive subjects in Madrid].
AB  - BACKGROUND: The rate of progression to AIDS in HIV-1 infected subjects is
      variable, and circumstances associated with more rapid or slow development of
      severe immunodeficiency might be grouped in three categories; environmental
      cofactors, host features, and particular virulence of the virus itself.
      Currently, it is not yet clear the the relative impact of each one. PATIENTS AND
      METHODS: A cross-sectional study was done in a cohort of 1,783 IV-1 infected
      persons from three centers located in Madrid, mainly devoted to attend persons at
      risks for HIV infection. Long-term nonprogressors (LTNP) were defined as those
      with more than 8 years of confirmed HIV seropositivity, and CD4+ T-cell count
      above 500 x 10(6)/I in the absence of antiretroviral therapy or symptoms
      suggesting immunodeficiency. Rapid progressors (RP) were those with less than 5
      years from seroconversion and repeatedly current CD4+ T-cell count below 200 x
      10(6)/I. An analysis of different epidemiological, immunological and virological
      features was performed comparing LTNP and RP. RESULTS: Among 1,783 HIV (+)
      subjects studied, 100 (5.6%) fulfilled criteria for LTNP and 12 (0.7%) for RP.
      Among LTNP, stabilized CD4 slope was seen in 16 (33%) out of 48 after more than 8
      years of infection. Variables statistically associated with LTNP were: past
      history of intravenous drug addiction (80% of them), male gender (79% of them),
      high alcohol intake (48% of them), HIV-1 non-syncitium inducing viral phenotype,
      and very low or undetectable HIV-1 plasma viremia. In contrast, variables
      associated with RP were: infection by sexual contact (75% of cases), female
      gender (50% of them), syncitium-inducing viral plenotype, and high titers of
      plasma viremia. The CD4/CD8 ratio below 1 was seen in all RP and in 88% of LTNP.
      However, a preferent depletion of CD4+ cell occurred in the first group, instead
      of an enhancement of the CD8 T-cell count in LTNP. The prevalence of serological
      markers for hepatotropic viruses and other potential infectious cofactors was not
      higher in RP. CONCLUSIONS: Multiple factors seems to account for the different
      rate of disease progression observed in HIV-1 infected persons. The dynamic
      equilibrium between the immune system and the virulence of the virus seem to be
      influenced--but not determined--by environmental infectious or non infectious
      cofactors.

PMID- 9019603
TI  - [Use of the NNIS index for determining the intrinsic risk of surgical infection].
AB  - BACKGROUND: To perform valid comparisons of rates of surgical wound infection
      (SWI) methods of adjustment must be carried out to eliminate the bias produced by
      the different profile of patients attended. MATERIAL AND METHODS: We studied
      retrospectively the SWI which occurred in 2,651 anaesthetized operations. The
      rates of SWI were analyzed according to the National Nosocomial Infection
      Surveillance-derived risk index (NNIS risk index). RESULTS: The average rate of
      SWI was 5.1%. The tree components of the NNIS risk index (contaminated or dirty
      surgical operation, ASA preoperative score > or = 3, time of anaesthesia > of the
      percentile 75th) were each one independent and they showed similar risks of
      surgical infection (odds ratio 1.6, 1.9, and 2.1 respectively). The rates of SWI
      in each level of the NNIS risk index were: index 0: 3.3%; index 1: 5.6%; index 2:
      10.8%; index 3: 3.0%. The rates of SWI showed a good correlation with the NNIS
      risk index (gamma coefficient: 0.35 SE: 0.07). In addition, the index determined
      growing rates of SWI at each level of the traditional classification of
      operations (except in the contaminated ones), in the majority of the main
      operative procedures and among operations of abdominal and extraabdominal
      localizations. CONCLUSIONS: The NNIS risk index is a better indicator of the
      intrinsic risk of patients than the traditional surgical wound classification
      alone.

PMID- 9019604
TI  - [Effectiveness of dermatologic minor surgery in the office of the family
      physician and patient satisfaction in relation with ambulatory surgery].
AB  - BACKGROUND: The minor surgery by family physicians increase the primary care
      competences. The purpose of this work is to prove patients' satisfaction and
      minor surgery effectiveness practiced by family physicians in health centers with
      respect to ambulatory's general surgeon. MATERIAL AND METHODS: Case-control
      retrospective study, comparing dermatological surgical procedures performed by 4
      family physicians and 8 3rd-year Family Physician residents with surgical
      procedures wade made by a surgeon over one a year period. Variables analysed
      include: descriptive samples homogeneity, surgery effectiveness (waiting time,
      esthetic results, healing time and number of visits, and histopathologic
      correlation) and patients' satisfaction (with the waiting time, with the results
      of surgery and with the physician). RESULTS: Minor surgical procedures carried
      out by 146 family physicians and 61 general surgeons were compared, in congruence
      with the analyzed descriptive homogeneity's parameters. Family physicians average
      waiting time was the lower, with a mean of 45 days less than the surgeon.
      Patient's satisfaction with the physician was higher when family physician were
      involved (p < 0.001); the same could be applied for the waiting time (p < 0.001).
      There were no significant differences over the effectiveness and patients'
      satisfaction. CONCLUSION: The dermatologic minor surgery by family physician is
      effective, satisfactory for patients, and has less waiting time. This results
      justify the introduction of minor surgery in the family physicians office.

PMID- 9019605
TI  - [Patients infected with HIV-1: why some speedsters and others marathon runners?].

PMID- 9019606
TI  - [Myositis caused by Pleistophora in a patient with AIDS].
AB  - The third case in the literature is reported of an infection produced by
      Pleistophora. The clinical detail of the three cases are discussed. Two of the
      patients-including the reported one-were infected by HIV. All patients suffered
      from myositis with fever, resting and at palpation myalgia, and progressive
      weakness. Blood tests showed anaemia and high levels of muscle enzymes. Necrotic
      muscle fibrosis induced disabling contractures. Diagnosis was obtained by
      detecting the protozoon in a muscle biopsy. The spores may be detectable by means
      of different staining methods at light microscopy although electron microscopy
      remains the most reliable technique. Since this is such a rare condition there is
      no known treatment. Whether the albendazole could be as useful as occurs in
      patients infected by other genera of microsporidia in still uncertain.

PMID- 9019607
TI  - [1995 Spanish consensus for the evaluation of obesity and to carry out
      epidemiologic studies. Spanish Society for the Study of Obesity].

PMID- 9019608
TI  - [Fever and abdominal pain in a patient with human immunodeficiency virus
      infection and Burkitt's lymphoma].

PMID- 9019609
TI  - [Mixed hepatitis induced by azathioprine].

PMID- 9019610
TI  - [Clinical usefulness of the free and total prostate specific antigen ratio in the
      diagnosis of cancer of the prostate].

PMID- 9019611
TI  - [Chlamydia trachomatis pneumonia in the adult].

PMID- 9019612
TI  - [Treatment of refractory autoimmune thrombocytopenic purpura with cyclosporin and
      interferon].

PMID- 9019614
TI  - [Brown spider bites].

PMID- 9019613
TI  - [Are useful the theoretical formulas for the calculation of the concentrations of
      inhaled nitric oxide?].

PMID- 9019615
TI  - Proceedings and abstracts of the XIII Congress of the Spanish Society of Clinical
      Pharmacology. Barcelona, Spain, November 27-29, 1996.

PMID- 9019616
TI  - Professional prospects in clinical pharmacology. An experience within primary
      health care.

PMID- 9019617
TI  - Professional prospects in clinical pharmacology. An experience within the
      regulatory authority.

PMID- 9019618
TI  - Professional prospects in clinical pharmacology. An experience within the
      pharmaceutical industry.

PMID- 9019619
TI  - Professional prospects in clinical pharmacology. History and present situation in
      Spain.

PMID- 9019620
TI  - Professional prospects in clinical pharmacology. An experience within the
      hospital.

PMID- 9019621
TI  - Advertisements in the Laryngoscope. Clinical confirmation.

PMID- 9019622
TI  - Poe's death remains a mystery.

PMID- 9019623
TI  - [Prion diseases].

PMID- 9019624
TI  - [Digitalization of histological images as a method of quantifying the
      demyelinating process].
AB  - The basic aim of this paper was to check the hypothesis whether after head trauma
      the brain tissue looses myelinic membrane which surrounds the axon, and if this
      possibly established loss can be quantified, that is if it is possible to
      determine the degree of disintegration. One of the aims was to examine this
      method itself. The gathered results show that both the hypothesis and the aims
      were justified. It has been established that the diffuse axonal lesion in the
      examined samples reflects in a loss of axon's myelinic membrane. The loss was 50%
      greater in the test group in regard to the control group. To digitalize
      histologic pictures we have used Laser Scanner Densitometry Station and software
      by Biomed. In regard to medical jurisprudence, the laser scanner densitometry
      offers more relevant data in cases apparently unclear and in sudden deaths after
      head injuries. Application of this method and further investigations will be
      directed to further attempts to clear up connections between the mechanism of
      injury and degree of biologic response of the brain tissue.

PMID- 9019625
TI  - [Functional, organic and histologic changes in the stomach in diabetic patients
      in relation to the presence of diabetic neuropathy].
AB  - Functional, organic and histological gastric changes were investigated in
      relation to the presence of autonomic neuropathy in 105 noninsulin-dependent
      diabetics (20 with autonomic neuropathy, 35 with peripheral neuropathy, 30 with
      both peripheral and autonomic neuropathy and 20 without neuropathy) and 40
      control persons. The diagnosis of autonomic neuropathy was assessed by
      parasympathetic test of cardiovascular reflexes and peripheral neuropathy by
      classical neurological examination and EMG (Electromyogram). All subjects were
      examined by radiologic and endoscopic methods with gastric biopsy specimens for
      histologic and immunocytochemical analysis. The results of investigation showed
      that functional abnormalities, hiatus hernia (55%) and pylorospasm (50%) occur
      more frequently in patients with autonomic neuropathy. Gastritis, duodenal ulcer
      (5%) and polyps (25%) are significantly more frequent. Atrophic gastritis type A
      (20%) was more frequent in diabetics with autonomic neuropathy than in other
      diabetics, as well as other types of gastritis. Immunocytochemical analysis
      showed the presence of rare, pale ECL (Extensor Caudae Lateralis) cells in corpus
      and pale, hypogranulated G cells in antrum and hyperplasia and metaplasia of EC
      (Embryonal carcinoma) cells in antrum of the stomach. Functional, organic and
      histologic changes in patients with diabetic autonomic neuropathy suggest that
      the systemic investigation of the Gut is very important in such patients.

PMID- 9019626
TI  - [The ANLL-NS 02 protocol for individualized therapy in acute nonlymphoblastic
      leukemia].
AB  - ANLL-NS-02 program is intended for individualized therapy of patients with acute
      non-lymphoblastic leukemia. The program itself is based on a net of prognostic
      models providing prompt prognosis of bad outcome of the disease as well as their
      prevention or early treatment. Specific prevention of early death is conducted
      prior to and during the induction therapy. Prevention of resistance to cytostatic
      drugs is based on evaluation of the early effect of the first induction
      chemotherapy with three cytologic-mathematical parameters. Remission
      consolidation consists of two individualized courses. Older patients undergo
      maintenance therapy which differs in clonal and nonclonal remissions. Optimal
      time to perform bone marrow transplantation is determined by mathematical models
      based on clinical data. In patients with high risk of leukemic relapse,
      transplantation is performed in the first remission, while in others it is
      performed in eventual relapse. Parts of ANLL-NS-02 program are computerized and
      adapted for clinical utilization. This program has been used at our institution
      for 5 years and results have confirmed advantages of individualized therapy over
      standard protocols in treating acute non-lymphoblastic leukemia.

PMID- 9019627
TI  - [Correlation between echocardiographic changes and parameters of pulmonary
      function in patients with arterial hypertension].
AB  - This study comprised 30 patients with mild or moderate arterial hypertension
      (according to classification of the World Health Organization) in whom some
      echocardiogram and parameters of the lung function were studied in order to
      establish correlation between them. A good correlation exists between LV (left
      ventricle) mass index and vital capacity (r = 0.562, p < 0.01), ejection fraction
      and forced mid expiratory flow (r = 0.717, p < 0.01), LV mass index and Tiffenau
      index (r = 0.620, p < 0.01), shortening fraction and forced mid expiratory flow
      (r = 0.591, p < 0.01), airways resistance and posterior wall thickness (r =
      0.591), p < 0.01) and between LV mass index and total lung capacity (r = 0.821, p
      < 0.01). There was not a good correlation or it was not significant (p > 0.05)
      between other echocardiographic changes and lung function tests.

PMID- 9019628
TI  - [Modern radiologic diagnosis of prostatic diseases].
AB  - Prostatic pathology presents one of the key elements of morbidity in adult and
      older males. In developed countries malignant prostatic tumors are the third most
      common cause of death in males older than 55 years of age. New diagnostic
      procedures such as transabdominal and transrectal ultrasound, computerized
      tomography and magnetic resonance enable direct prostatic visualization thus
      better and more efficient diagnostics. This study offers a review and schedule of
      diagnostic procedures which enable early detection and classification of
      prostatic diseases.

PMID- 9019629
TI  - [Measurement of efficiency and quality of work in hospitals and ambulatory
      facilities].
AB  - Facing high-cost health care and slow rate of economic growth, great attention
      must be paid to efficiency and quality of care in hospitals and ambulatory care
      facilities. This is a problem particularly in developing countries where extreme
      sums of money are spent on developing hospital capacities, whereas primary health
      care facilities are insufficient causing significant social differences among
      health care beneficiaries. At the same time, there exists a certain discontent
      because principles of equality, efficacy, efficiency and quality of health care
      including satisfaction of patients obtaining health care, are not pointed out in
      providing health care. Up to recent times it has been very hard to evaluate both
      qualitative and quantitative efficiency and quality of work in health care
      institutions, but today it is possible because the World Health Organization
      created indicators for this kind of evaluation.

PMID- 9019630
TI  - [Rehabilitation of war injuries associated with peripheral nerve lesions].
AB  - The objective of this study was to examine frequency, characteristics and results
      of hospital medical rehabilitation of war injured patients with peripheral nerve
      lesions. War injured patients with peripheral nerve lesions make 10.83% of all
      war injured hospitalized patients. The major etiologic factor in these injuries
      were firearms. Most injured aged 26 to 36 years of age, whereas men were injured
      more often than women. The injuries were primarily localized in the regions of
      axilla, upper leg and upper arm. In regard to upper extremities injuries most
      often occurred on the right side or bilaterally. Injuries of n. ischiadicus,
      combination of n. ulnaris and n. medianus occurred more frequently than injuries
      of other peripheral nerves. Electromyoneurographic and neurosurgical findings
      point to frequent partial-severe and complete nerve lesions. After hospital
      treatment lasting 4.6 months on the average, unsatisfactory functional reparation
      was found in most injured patients. This demands further control, continuous
      medical as well as social and professional rehabilitation.

PMID- 9019631
TI  - [Clinical characteristics of trichinosis].
AB  - 91 patients with trichinosis were treated at the Clinic of Infectious and
      Dermatovenereology Diseases in Novi Sad during a one-year period. In 64% of
      patients the onset was intestinal, while in 36% it was invasive. Diarrhea (in
      28.89%) and abdominal pain (in 22.22%) are the most common symptoms of the
      intestinal stage. Nausea, vomiting and opstipation are less common. The main
      symptoms of the invasive stage are myalgia (65.54%), high temperature and eyelid
      edema (57.78%). Facial edema (38.89%), general weakness (24.44%), conjunctivitis
      (15.56%) and rash (8.89%) are somewhat less common. Heavy sweating, headache,
      nervousness, psychic instability and fast forgetting occur in a small number of
      treated patients. Myocarditis and encephalitis occurred in 3.33% of patients.
      There were 43.33% of patients with mild clinical picture, 40% with mild-to-severe
      and 16.66% with severe clinical picture. 54.44% of patients were males and 45.56%
      were females, and it can be said that sex did not influence the severeness of the
      clinical picture. The youngest patient was 5 years of age, the oldest 72. Most
      patients were 21-50 years of age but we did not establish statistical importance
      between clinical picture severeness in regard to age. The shortest period of
      incubation was 5 days, the longest 40 days. Average incubation period was 18.05
      days (x = 18.05). Studying period of incubation and severeness of the clinical
      picture we established the following (x2 = 28.535). The shorter the incubation
      period, the severer the disease.

PMID- 9019632
TI  - [Diagnostic approach to von Willebrand's disease in childhood].
AB  - Von Willebrand's disease seems to be the most common hereditary bleeding disorder
      in children. Every form of this disease is based on quantitative or qualitative
      disorder of von Willebrand's factor influencing adhesion of thrombocytes (primary
      hemostasis) and stabilization FVIII:C in circulation (secondary hemostasis). We
      present contemporary knowledge on epidemiologic investigations, molecular
      biology, classification and rational diagnostic approach to von Willebrand's
      disease in children. We also report on evaluating laboratory tests' reliability
      in 51 examined children with von Willebrand's disease. It can be concluded that
      most laboratory tests are highly specific and significant for diagnosis.
      Determination of vWF activity has optimal value for establishing laboratory
      diagnosis of von Willebrand's disease; RIPA and multimer analysis are valuable
      for subtype classification.

PMID- 9019633
TI  - [Epidemiology of skin tumors of the face and neck (ORL region) treated surgically
      from 1981 to 1990].
AB  - This paper reviews basic epidemiologic characteristics of 1549 changes located on
      face, neck and lips and surgically treated at the ORL Department of the General
      hospital in Subotica during the period 1981-1990. We analyzed the following
      parameters: frequency of certain diseases, their distribution according to the
      studied period of time, sex and age distribution, place of living, interaction
      between malignant and benign tumors as well as eventual influence of some
      meteorologic factors in regard to the previous 10-year period. It has been
      established that malignant tumors, precancerous and benign tumors make up 70% of
      surgically treated patients. There has been no statistically significant
      difference between sexes or according to the place of living. Most patients are
      in the eighth decade. It has been established that there is a slight trend of
      increase in regard to the number of operated patients in some studied years both
      in malignant and benign tumors, but there seems to be no connection between the
      number of surgically treated patients and analyzed meteorologic factors.

PMID- 9019634
TI  - [Ultrasonographic diagnosis of acute appendicitis].
AB  - 128 patients aged from 2 to 18 with symptoms of acute appendicitis were studied
      prospectively. Surgical procedure was performed in 58 patients (i.e.
      appendectomy). In 5 patients surgical findings were catarrhal inflammation, in 14
      phlegmonous, in 9 gangrenous, in 15 perforated and in 13 no inflammation
      occurred. In 2 cases abscess periappendiceal was found intraoperatively. We
      considered as visualized only those appendices that were intraoperatively found
      at places ultrasonographically described. Ultrasonographic visualization was
      successful in 91.37%. The most relevant criteria for ultrasonic evaluation of the
      inflammation is noncompressibility noted in 97.67% of cases of appendicitis. The
      second criteria is thickened wall noted in 86.04% of patients. Ultrasonographic
      diagnosis of the abdominal fluid collections is confident: sensitivity 0.85,
      specificity 0.91. The diagnostic value of ultrasound findings in acute
      appendicitis is high: sensitivity 0.87, specificity 0.84. That is why routine
      ultrasound diagnostic examination in acute atypical appendicitis is recommended.

PMID- 9019636
TI  - [Ovulation induction in women in the in vitro fertilization program].
AB  - In-vitro fertilization presents a method of assisted reproduction where fusion of
      two gametes (fertilization) occurs in laboratory conditions. In this way part of
      the process which normally happens in the fallopian tube is being imitated. By
      ovulation the number of follicles increases, thus increasing the number of
      oocytes, that is the number of embryos and at the same time increasing chance of
      pregnancy. Ovulation induction was achieved by: clomiphene citrate (CC), human
      menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG) and luteinizing
      hormone-releasing hormone (LHRH). Our trial compared effects of three induction
      schemes: HMG-hCG; CC-hMG-hCG and LHRH-hMG-hCG. We compared the following
      parameters: total number of follicles, number of mature follicles (16mm with
      simultaneous estradiol level 350pg/ml per follicle), number of aspirated oocytes
      as well as the number of embryos produced by insemination of aspirated oocytes.
      Our examination revealed that there was no significant difference in number of
      follicles, aspirated and produced oocytes in patients undergoing stimulated
      ovulation scheme CC-hMG-hCG in regard to those with hMG-hCG schemes. In patients
      undergoing LHRH-hMG-hCG scheme the number of follicles was decreased and there
      were less oocytes, but the number of developed embryos after oocytes insemination
      was increased. This leads to the conclusion that in-vitro fertilization depends
      on quality, not only the number of oocytes obtained by LHRH agonists induction.

PMID- 9019635
TI  - [Acute anterior myocardial wall infarct caused by aortic dissection].
AB  - Acute myocardial infarction and aortal dissection are two different entities
      mostly occurring separately. According to the fact that both are severe diseases
      their simultaneous occurrence and interdependence present high risk for patients
      and a differential diagnostic dilemma for physicians. The case of S.J., a 52-year
      old female patient is a combination of aortic dissection and acute myocardial
      infarction caused by dissection of aorta and retrograde dissection of the left
      coronary artery main branch.

PMID- 9019637
TI  - [Guidelines for management of home ventilation patients. Home and Long-Term
      Ventilation Working Group].

PMID- 9019638
TI  - [Conversion rate and prevention of recurrence of paroxysmal and sustained atrial
      fibrillation or atrial flutter with verapamil/quinidine].
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia,
      occurs in 0.4% of the adult population and in as many as 2% to 4% of those 60
      years of age or older. PATIENTS AND METHODS: We studied retrospectively 102
      patients, 76 males, 26 females, mean age 56 +/- 12 years, with paroxysmal or
      sustained atrial fibrillation or atrial flutter (AFlut) treated with
      verapamil/quinidine (Cordichin) (dosage 3 to 5 times 1 tablet/day). Coronary
      artery disease was present in 39 patients, dilated cardiomyopathy in 8 patients,
      valvular disease in 16 patients and various etiologies were present in 13
      patients. Twenty-six patients had no discernable heart disease ("Jone atrial
      fibrillation"). Patients with long QT-syndrome (QT-duration > or = 500 msec; QTc
      > or = 440 ms) were excluded from this study. RESULTS: Using verapamil/quinidine
      conversion to sinus rhythm (SR) was possible in 64 patients (63%) within 2 +/- 1
      day (range 1 to 6 days). The mean given dosage of quinidine was significantly
      higher in patients converted to sinus rhythm (762 +/- 129 mg) compared to those
      without successful conversion (638 +/- 161 mg) (p < 0.001). Diameter of left
      atrium and left ventricle as well as the degree of heart failure did not
      influence cardioversion rate significantly. During a mean follow-up of 34 +/- 32
      months (range < 1 to 129 months), sinus rhythm remained constant in 28/64
      patients (44%) with verapamil/quinidine in whom conversion to sinus rhythm was
      successful. During follow-up, side effects were present in 20/64 patients who
      were discharged with verapamil/quinidine: in 2 patients (2%) a torsade de pointes
      tachycardia was observed (1 patient died suddenly); gastrointestinal side effects
      were observed in 5 patients (5%); 4 patients had sinuatrial and 3 patients
      atrioventricular conduction disturbances. An increase in ventricular ectopic
      beats were present in 3 patients and allergic reactions occurred in 3 patients.
      CONCLUSIONS: The present data show that verapamil/quinidine is effective in
      conversion of atrial fibrillation and atrial flutter to sinus rhythm and is
      associated with an acceptable efficacy rate in preventing recurrences of atrial
      fibrillation or flutter. Final conclusions concerning side effects are only
      possible in prospective studies that are ongoing at the present time.

PMID- 9019640
TI  - [Nephrology update--IV. Rapidly progressing glomerulonephritis].

PMID- 9019639
TI  - [Combination antihypertensive therapy in patients with an increased risk
      profile].
AB  - BACKGROUND: Antihypertensive drug combinations have two major advantages: First,
      dosage of the single components can be reduced, and second, putative side effects
      can be minimized. Therefore, we analysed in a cohort of patients with multiple
      cardiovascular risk factors the metabolic effects of two fixed antihypertensive
      drug combinations. PATIENTS AND METHODS: 225 patients with essential hypertension
      (dBP > or = 95 < or = 115 mm Hg) and adipositas (BMI 30.6 +/- 2.5) were randomly
      treated during 6 months with either quinapril and hydrochlorothiazide (HCTZ) or
      with metoprolol and hydrochlorothiazide. Compared with healthy controls, patients
      exhibited significant elevated concentrations of triglycerides (226 +/- 86 vs.
      146 +/- 73 mg/dl) and fasting insulin (22.2 +/- 1.8 vs. 9.8 +/- 4.6 microU/ml).
      RESULTS: The antihypertensive effects and the tolerance of both substances were
      good and comparable after 3 and 6 months. Serum triglycerides increased during
      metoprolol/hydrochlorothiazide treatment (230 +/- 81 vs. 244 +/- 185 mg/dl;
      median 174 vs. 204; + 17%), as well as during treatment with
      quinapril/hydrochlorothiazide (222 +/- 155 vs. 235 +/- 162 mg/dl; median 166 vs.
      174; + 5%). Fasting blood glucose levels, insulin, fructosamine, HbA1c and free
      fatty acids remained unchanged. In a subgroup of 88 postmenopausal women with
      upper body obesity (WHR > 0.85) treatment with quinapril/hydrochlorothiazide
      normalized the VLDL-triglyceride/VLDL-cholesterol ratio (3.8 vs. 5.9, p < 0.05),
      whereas the ratio only increased from 3.6 to 4.2 in the
      metoprolol/hydrochlorothiazide group. These changes in the ACE-inhibitor group
      were due to a decrease in VLDL-cholesterol (41.4 +/- 4.2 vs. 33.9 +/- 9.6).
      CONCLUSION: These data demonstrate that quinapril or metoprolol in combination
      with hydrochlorothiazide do not differ significantly with regard to their effects
      on blood-pressure lowering, lipoprotein profile, and glucose metabolism. Only in
      the subgroup of adipose postmenopausal women, the modulated VLDL-composition
      might suggest the elimination of atherogenic VLDL-remnants/IDL during
      quinapril/hydrochlorothiazide treatment.

PMID- 9019641
TI  - [Type II diabetes and hypertension].

PMID- 9019642
TI  - [Adjuvant systemic therapy of breast carcinoma].

PMID- 9019643
TI  - [Ubiquitous mycobacteria: clinical and microbiological aspects].

PMID- 9019644
TI  - [Thoughts on the correlation of hope, trust, responsibility and shame in the
      relationship between patients and their physicians].

PMID- 9019645
TI  - [Cholestasis--therapy].

PMID- 9019646
TI  - [Different phenotypes of type IXb glycogenosis (phosphorylase-b-kinase
      deficiency) in adult- and early childhood].

PMID- 9019647
TI  - [Cost of asthma therapy in relation to severity. An empirical study].
AB  - BACKGROUND: The aim of asthma therapy, i.e. the permanent elimination of the
      patient's symptoms, is as a rule, achievable over the long-term only with the aid
      of anti-inflammatory drugs. As well as medical, this approach also has
      considerable economic implications. The comparatively low compliance among
      asthmatics makes treatment in this context all the more difficult. An alternative
      that presents itself is the use of combination preparations, a mixture of a long
      term prophylactic and a therapeutic agent. PATIENTS AND METHODS: With the aid of
      standardised questionnaires, data were acquired from 216 patients and assigned to
      subgroups in accordance with the degree of severity of the asthma. The patients
      were treated in the offices of a total of 23 GPs and internists selected at
      random from a complete list of all relevant practices in Germany. The use of
      resources, i.e. all diagnostic and therapeutic measures, was recorded
      retrospectively for a period of 1 year. In this way, all those resources of
      relevance to the health insurance carriers used during the observation period
      were identified. In addition to direct costs, so-called indirect costs were also
      estimated, i.e. in the present study the productivity loss to the economy due to
      illness-related absence from work. RESULTS: The annual cost of treating adult
      asthmatics was calculated to be DM 3,339 for level 1 severity, DM 5,260 for level
      2 severity and DM 12,016 for level 3 severity. As the illness progresses in
      particular the direct cost of inpatient care and the indirect costs rise
      disproportionately. The yearly expenditure for women sufferers is about DM 800
      more than for male sufferers. The direct cost of asthma treatment in children
      amounts to DM 2,950 for level 1, DM 3,225 for level 2, and DM 4,811 for level 3,
      severity. Here, drug-related costs in particular, rise significantly as the
      disease progresses. CONCLUSION: One of the results of the present study is the
      fact that for asthma sufferers in general, there is a positive correlation
      between average total costs and degree of severity. It may thus be postulated
      that preventive medical treatment of asthma that slows the progression of the
      illness, together with appropriate patient instruction, would have a positive
      effect on the total expenditure per patient. If, for example, the appropriate use
      of drugs in combination with patient instruction improved the compliance of
      asthmatics, lower treatment costs and a better quality of life for the patient
      could be expected.

PMID- 9019648
TI  - Appetite-suppressant drugs and primary pulmonary hypertension.

PMID- 9019649
TI  - Appetite-suppressant drugs and primary pulmonary hypertension.

PMID- 9019650
TI  - Appetite-suppressant drugs and primary pulmonary hypertension.

PMID- 9019651
TI  - Appetite-suppressant drugs and primary pulmonary hypertension.

PMID- 9019652
TI  - Appetite-suppressant drugs and primary pulmonary hypertension.

PMID- 9019653
TI  - Appetite-suppressant drugs and primary pulmonary hypertension.

PMID- 9019654
TI  - Invasive group A streptococcal infections.

PMID- 9019655
TI  - Invasive group A streptococcal infections.

PMID- 9019656
TI  - Invasive group A streptococcal infections.

PMID- 9019657
TI  - Escherichia coli and the hemolytic-uremic syndrome.

PMID- 9019658
TI  - Escherichia coli and the hemolytic-uremic syndrome.

PMID- 9019659
TI  - Carotid-artery dissection after a prolonged telephone call.

PMID- 9019660
TI  - [Pumps, channels and transporters of the renal tubule: a growing field of
      investigation].

PMID- 9019661
TI  - [Polarity of epithelial cells. Role of the actin microfilament system].
AB  - Polarized epithelial cells display a cell surface organization well adapted to
      their specialized functions in transports and exchanges with the external
      "milieu". The numerous microvilli that cover the apical plasma membrane arc
      supported by bundles of actin microfilaments and associated actin binding
      proteins. Three independent experimental approaches have been used to unravel the
      function(s) of villin: a) overexpression of the villin gene; b)inhibition of
      villin production with a villin antisense RNA; c) disruption of the villin gene
      by homologous recombination. The role of ezrine, a protein able to interact both
      with components of the plasma membrane and with actin microfilaments, in cellular
      morphogenesis and the signal transduction cascade elicited by the scatter factor
      (HGF) and its receptor, has also been investigated with molecular cell biology
      approaches.

PMID- 9019663
TI  - [Regulation and physiopathology of phosphate transport].
AB  - Renal phosphate transport is subjected to a fine tuning which involves hormones
      and local mediators and results in adaptation of excretion to dietary contents.
      Recent insights into the molecular structure of phosphate transporters have shed
      light on the mechanisms which underline the effects of these mediators. Another
      important repercussion of these advances is the identification of pathological
      states such as renal phosphate leaks and the elaboration of diagnostic and
      therapeutic strategies aiming to improve these troubles.

PMID- 9019662
TI  - [Endocytosis and receptors: molecular and physiological aspects].
AB  - One of the functions of the proximal tubule cells is to internalize and degrade
      proteins that have not been retained by the glomerulus. The magnitude of the
      amounts of protein reabsorbed (several hundreds of milligrams per day) imply
      specific structures that favor endocytosis and recycling of plasma membrane
      components as well as the expression of specific molecules that play a role in
      the endocytic traffic and/or act as multiligand receptors. In this study we
      review recent data that link 2 high molecular weight glycoproteins, gp330/megalin
      (600 kDa) and gp280 (460 kDa) to the endolytic process in proximal tubule cells.

PMID- 9019664
TI  - [Molecular aspects of Na+/H+ exchange in the renal tubule: localization and
      adaptation to the acid-base state].
AB  - Na+/H+ exchangers (NHE) are plasma transmembrane proteins that exchange
      extracellular Na+ for intracellular H+. Several isoforms of these antiporters
      belonging to the same gene family have been cloned and four of them (NHE1 to
      NHE4) are expressed in the kidney. In the kidney, NHEs isoforms display different
      tubular and membrane (apical vs basolateral) localization and are involved in
      different functions: regulation of pH and cell volume, NH4+ secretion and NaHCO3
      and NaCl reabsorption. NHE3, which is the apical isoform of the proximal tubule
      and thick ascending limb of Henle, is involved in bicarbonate reabsorption and
      displays activation during metabolic acidosis. These recent data showing the acid
      activation of NHE3 suggest that NHEs isoforms could be involved in the pathogeny
      of tubular acidosis.

PMID- 9019665
TI  - [Urea transporters].
AB  - Water and urea use different pathways to cross biological membranes: channels and
      carriers. Numerous water channels were cloned (aquaporins); only two urea
      transporters are characterized in mammalians (UT2 and UT11) with sequence
      homologies suggesting two different carriers. This was confirmed by different
      localizations: UT2 was only found in renal medulla and probably was the AVP
      sensitive urea carrier while UT11 was found in testis, spleen, brain and kidney
      and represents the constitutive urea carrier described in red blood cell. UT2
      hybridized two transcripts, 4.1 kb and 2.9 kb. The large transcript expression
      was regulated by low protein diet whereas the short transcript was regulated by
      hydratation conditions. The heterologous expression into Xenopus oocytes showed a
      large increase of the urea uptake (UT2 > UT11), inhibitable by phloretin for UT11
      and UT2 and by pCMBS only for UT11. A saturable transport of thiourea was only
      observed into oocytes expressing UT11. Moreover, hUT11 is encoded by the kidd
      locus, but, Jk (a-b-) individuals, in the absence of this urea transporter did
      not present related pathology. Other carriers still have to be identified and
      characterized in different renal segments and other tissues.

PMID- 9019666
TI  - [The amiloride sensitive sodium channel].
AB  - The amiloride-sensitive epithelial Na+ channel is formed by the assembly of three
      homologous subunits alpha, beta and gamma. The channel is characterized by its
      sensitivity to amiloride and to some amiloride derivatives, such as phenamil and
      benzamil, by its small unitary conductance (approximately 5pS), by its high
      selectivity for lithium and sodium, and by its slow kinetics. The alpha, beta,
      and gamma proteins share significant identity with degenerins, a family of
      proteins found in the mechanosensory neurons and interneurons of the nematode
      Caenorhabditis elegans. They are also homologous to FaNaCh, a protein from Helix
      aspersa nervous tissues, which corresponds to a neuronal ionotropic receptor for
      the Phe-Met-Arg-Phe-amide peptide. All these proteins contain a large
      extracellular loop, located between two transmembrane alpha-helices. The NH2 and
      COOH terminal segments are cytoplasmic, and contain potential regulatory segments
      that are able to modulate the activity of the channel. In Liddle syndrome, in
      which patients develop a form of genetic hypertension, mutations within the
      cytoplasmic COOH terminal of the beta and gamma chains of the epithelial Na+
      channel lead to a hyper-activity of the channel. Epithelial Na+ channel activity
      is tightly controlled by several distinct hormonal systems, including
      corticosteroids and vasopressin. In kidney and colon, aldosterone is the major
      sodium-retaining hormone, acting, by stimulation of Na+ reabsorption through the
      epithelium. In the distal colon from steroid-treated animals, a large increase of
      the beta and gamma subunits transcription is observed, whereas the alpha subunit
      remains constitutively transcribed. In kidney, RNA levels of the three subunits
      are not significantly altered by aldosterone, suggesting that other mechanisms
      control Na+ channel activity in that tissue. In lung, the glucocorticoids are the
      positive regulators of the channel activity, especially around birth, and act via
      an increased transcription of the three subunits.

PMID- 9019668
TI  - [Pathological aspects of water transport in the collecting ducts].
AB  - In a normal adult subject, 12 liters of tubular urine with an osmolality of 100
      mmol/kg exit per 24 hours from the loop of Henle. The antidiuretic hormone
      arginine-vasopressin increases the water permeability of the renal collecting
      ducts and induces the reabsorption of 11 liters of water: the final urinary
      osmolality is 1200 mmol/kg for a urinary flow rate of 1 litre per 24 hours. In
      nephrogenic diabetes insipidus the urine cannot be concentrated maximally.
      Congenital nephrogenic diabetes insipidus is secondary to either mutations in the
      AVPR2 gene (Xq28) that codes for the vasopressin antidiuretic (V2) receptor or to
      mutations in the AQP2 gene (12q13) that codes for the vasopressin dependent water
      channel. AVPR2 mutations are numerous and diverse: 72 different putative disease
      causing mutations in the AVPR2 gene have been reported in 102 unrelated families
      with X-linked nephrogenic diabetes insipidus. AQP2 mutations are rare.
      Nephrogenic diabetes insipidus could also be secondary to lithium or
      demeclocycline administration and to hypokaliemia. Some of these conditions are
      inducing, experimentally, a downregulation of aquaporin II. We encourage
      physicians who follow families with hereditary nephrogenic diabetes insipidus to
      recommend molecular genetic analysis because early diagnosis and treatment of
      infants can avert the physical and mental retardation associated with episodes of
      dehydration.

PMID- 9019667
TI  - [Molecular and functional diversity of NA,K-ATPase and renal H,K-ATPases].
AB  - Potassium homeostasis is a determinant factor in the maintenance of many vital
      functions. Cell excitability, for instance, in striate and cardiac muscle, as
      well as in neurons, is dependent upon the ratio of potassium levels on either
      side of the plasmic membrane. Acute or chronic mechanisms of adjustment to
      disorders of bodily potassium balance exist in muscle, the kidney and distal
      colon. Na+K(+)-ATPase is involved in potassium transfers between the
      extracellular and intracellular compartments, in particular in muscle, enabling
      the creation of an appropriate trans-membrane K gradient. Na+K(+)-ATPase also
      participates in the development and maintenance of a transmembrane potassium
      electrochemical gradient necessary for potassium secretion processes in the
      kidney or distal colon. Colonic and renal H+K(+)-ATPases, so-called non-gastric
      H+K(+)-ATPases, are involved in the absorption of potassium from the
      gastrointestinal lumen or urinary fluid. They have an important role to play
      during chronic disorders, e.g. chronic bodily potassium depletion. Renal H+K(+)
      ATPases and Na+K-ATPase are P-ATPases, consisting of a heterodimer of two alpha
      and beta sub-units. Several isoforms have been identified, on both a molecular
      and functional basis, for both the alpha and beta sub-unit. These two ATPases
      form part of the Na+K(+)-ATPase/H+K(+)-ATPase gene group. These pumps share many
      structural and functional similarities, but also particular functional
      specificities, probably involved in separate physiological roles for each
      isoform. Four isoforms of the alpha sub-unit and two isoforms of the beta sub
      unit of Na+K(+)-ATPase have been identified. Sensitivity to ouabain, a Na+K(+)
      ATPase inhibitor, differs according to the alpha isoform present in the alpha
      beta heterodimer. It is also involved in the catalytic cycle and influences pump
      potassium affinity. Several H+K(+)-ATPases have been identified from a molecular
      standpoint: gastric H+K(+)-ATPases and a colonic H+K(+)-ATPase found more
      recently. Recent studies have shown that both these H+K(+)-ATPases exist in the
      kidney. "Gastric" H+K(+)-ATPase is active along the entire length of the
      collecting tubule, in rats exposed to a normal potassium intake. In contrast,
      colonic H+K(+)-ATPase is active only in the cells of the external medullary
      collecting duct. This activity cannot be detected in animals on a standard diet
      but is very powerfully induced by potassium depletion. Activity is independent of
      steroidal status and of aldosterone in particular. Identification of a molecular
      homologue in the bladder of the amphibian Bufo marinus (the functional equivalent
      of the cortical collecting duct of mammals) has enabled the development of
      functional tests by activity in the oocyte of Xenopus laevis. The use this
      functional approach has shown that bladder H+K(+)-ATPase, just like that of rat
      distal colon, is sensitive to ouabain, an inhibitor considered up to now to be
      specific to Na+K(+)-ATPase. In contrast, this H+K(+)-ATPase shows little or no
      sensitivity to Sch 28080, a "classical" gastric H+K(+)-ATPase inhibitor. It thus
      seems that two H+K(+)-ATPases, different from a molecular standpoint, exist in
      rat kidney. They differ in terms of their cellular activity, regulation and
      functional properties. This is strongly suggestive of a specific role of each of
      them in potassium homeostasis, a role which remains to be defined. The use of
      genetically modified animals, as well as of physiological studies more focussed
      on this question, should provide clarification of the specific functional role of
      each isoform of the alpha and beta sub-units of renal H+K(+)-ATPases and Na+K(+)
      ATPase. Extrapolation of these results to human pathophysiology is quite another
      challenge. Control of Na+K(+)-ATPase activity by endoouabain and its effects on
      cardiovascular pathophysiology must be identified. An H+K(+)-ATPase with
      molecular and functional characteristics similar to those of amphibian bladder
      and rat colon H+K(+)-A

PMID- 9019669
TI  - Special issue dedicated to Dr. Herman Bachelard.

PMID- 9019670
TI  - Compatibility of reduced glutathione (GSH) with different solutions currently
      used in anesthesia and reanimation.
AB  - BACKGROUND: Reduced glutathione (GSH) an antioxidant used for i.v. or i.m.
      administrations, prepared as powder to be diluted in distilled water just before
      injection (Tationil 600), could lose its antioxidant properties when added to
      various infusions currently utilized in anesthesia and reanimation. AIM OF THE
      WORK: Evaluate in vitro the compatibility of the compound marketed under the
      trade nome "Tationil 600" with the intravenous infusions in common use in
      anesthesia and reanimation. MATERIALS AND METHODS: 10 mg GSH (Tationil 600) were
      added to 10 ml of different solutions: 0.9% saline (I), 5% glucosate solution
      (II), Normosol-M and 5% glucose (III), 3.5% Emagel (IV), Propofol 10 mg/ml (V),
      in order to obtain a final solution containing 1 mg og GSH per ml of solution.
      The different solutions were incubated and aliquots taken at different times and
      analyzed. RESULTS: GSH in its commercial preparation proved to be compatible with
      all solutions examined with exception of solution III, because of the
      interference of sodium bisolfite. CONCLUSIONS: Reduced glutathione (Tationil 600)
      was compatible with solutions I, II, IV and V, used for i.v. administrations in
      anesthesia and reanimation, and revealed to maintain its antioxidant properties
      when studied over a period of 24 hours.

PMID- 9019671
TI  - [Traumatic rhabdomyolysis. A clinical case].
AB  - The authors report a case of post-traumatic rhabdomyolysis in a victim of a car
      accident who, after having being initially examined at an emergency ward, was
      sent home having been requested to return for a control visit a few days later.
      The patient did not attend the control visit on the appointed day but returned to
      the same emergency ward eight days after the accident suffering from vomiting,
      general malaise and violent pain in the left forearm that appeared swollen.
      Anamnesis revealed a severe condition of rhabdomyolysis with dehydration, pale
      red urine and general signs of marked renal insufficiency. Tests showed marked
      myoglobinemia and myoglobinuria, very high CPK, azotemia, creatinemia,
      transaminase and high diastasemia. Given the disappearance of peripheral pulse
      and the severe neurovascular impairment of the left forearm caused by edematous
      compression, it was decided to proceed to surgical decompression using extensive
      longitudinal fasciotomy under supraclavicular anesthesia. After surgery
      peripheral pulse returned to normal, as was confirmed by Doppler. After adequate
      hydration while renal insufficiency lasted, hemodialysis was commenced
      immediately and repeated during the following days. Given that all the tests had
      improved and results were virtually within the norm, the patient was transferred
      to the medical ward after eight days for continuation of therapy. It is important
      to underline the importance of possible signs, such as oleguria, dark urine,
      swelling and edemas of the limbs, in injured patients. If renal insufficiency
      occurs, it is important to commence early hemodialysis. On day 23 the patient was
      again transferred to the intensive care ward because he presented epigastric pain
      and vomiting. CAT showed acute pancreatitis which resolved leading to full
      recovery after 20 days.

PMID- 9019672
TI  - [Lactic acidosis induced by phenformin: a still forgotten iatrogenic
      complication].
AB  - Phenformin, a drug used in the treatment of diabetes mellitus frequently
      associated with potentially fatal cases of lactic acidosis, has been removed from
      market in the USA and several European countries. However, cases of lactic
      acidosis are still reported in countries where phenformin is available, either
      because well-known contraindications for its use are not observed, or because the
      prodromic syndrome of the lactic acidosis is not diagnosed. This study describes
      two cases of lactic acidosis, the treatment used and the final outcome. The
      authors point out that plainly evident contraindications were ignored in both
      cases, while the prodromic syndrome remained unrecognized even by specialists.
      The management of lactic acidosis continues to be a challenge. There is no
      optimal treatment and early recognition is essential. The authors call for
      greater attention in the use of phenformin and its eventual removal from market,
      especially in the light of alternative therapies which prove to be equally valid
      and easier to administer.

PMID- 9019673
TI  - [A case of secondary misplacement of the selective bronchial tube in thoraco
      pulmonary surgery].
AB  - The authors, after a short synthesis of the causes of secondary misplacement of
      the selective bronchial tube in thoracic surgery, describe a clinical case. A
      patient, after the induction of anaesthesia and selective intubation with Carlens
      tube, undergoes a surgical procedure of right upper lobectomy. During this
      procedure, a very serious O2 desaturation stands out and only at the end of the
      procedure, after X-ray examination, it is possible to understand. The cause of
      the O2 desaturation is a secondary movement of the bronchial tube. The authors
      come to the conclusion that to diagnose the secondary misplacement of the
      bronchial tube during the surgical procedure it should be useful perioperative
      fiberoptic bronchoscopy.

PMID- 9019674
TI  - [Critical course of a case of idiopathic pulmonary fibrosis].
AB  - The authors present a case of idiopathic pulmonary fibrosis with an unusual onset
      in the form of acute interstitial pneumonia. On being admitted to hospital the 53
      year-old woman presented an altered breathing pattern which initially required
      oxygen therapy using Venturi's oxygen mask followed by sedation and mechanical
      ventilation with appropriate FiO2 to guarantee adequate pO2 and arterial
      saturation. For diagnostic purposes bronchiolar and alveolar lavage was
      immediately performed together with transbronchial biopsy during the course of
      fibrobronchoscopy. The results of these tests revealed a syndrome of interstitial
      pneumonia and widespread alveolar lesion with an enhanced lymphocyte population.
      Antibac-terial and immunosuppressive therapy (6-methylprednisolone and
      cyclophosphamide) commenced on the basis of these tests caused a temporary
      improvement in blood-gas parameters and parenchymal thickening. But in spite of
      treatment the patient's cardiocirculatory and respiratory conditions
      deteriorated, causing death. This case report raises a number of different
      questions regarding both diagnosis and treatment. With regard to diagnosis it is
      worth underlining the absence of hyaline membrane, pathognomonic of widespread
      alveolar lesions, in biopsies removed while the patient was still alive. With
      regard to treatment, in addition to specific antibiotic and immunosuppressive
      therapy, the authors consider that surfactants might be of some help given that
      widespread alveolar damage can be attributed to pulmonary fibrosis.

PMID- 9019677
TI  - Parkinson's disease.

PMID- 9019675
TI  - [Thrombocytopenia and thrombophilic state in heparin therapy].
AB  - The authors report two clinical cases of thrombocytopenia and thrombosis which
      occurred during profilaxys and therapy with heparin. The mechanisms involved are
      reviewed and the possible therapeutic role of heparin-like drugs is discussed
      according to data presented in the international literature.

PMID- 9019679
TI  - Concerns about future NP education.

PMID- 9019676
TI  - [Adsorption of volatile anesthetics on activated charcoal. Efficiency of an
      experimental filter during low-flow circuit ventilation].
AB  - The inclusion of charcoal filters in the anaesthetic low-flow systems contributes
      to the acceleration of the kinetics of isoflurane (Forane). In fifty-four
      subjects, scheduled for extra- and intracranial surgery, ventilated with a low
      flow system (Ohmeda Excel OAV7750 with rebreathing cassette) with a mean total
      flow of 0.7 1/min, the experimental charcoal cartridge showed: (a) a good
      adsorbent power (awakening within 5-6 minutes from the inclusion of the cartridge
      into the circuit) and (b) efficiency (adsorbent power unchanged until the sixth
      application). The use of charcoal during low-flow anaesthesia is both useful and
      economical.

PMID- 9019678
TI  - Knowledge of testicular self-exam.

PMID- 9019680
TI  - A model of a successful clinic.

PMID- 9019682
TI  - Adopt the singular title: advanced practice nurse.

PMID- 9019683
TI  - NPs must exercise their power.

PMID- 9019681
TI  - Primary care to the underserved through community empowerment.

PMID- 9019684
TI  - Nurse practitioners--where do they belong within the organizational structure of
      the acute care setting?

PMID- 9019685
TI  - Nurse practitioners--where do they belong within the organizational structure of
      the acute care setting?

PMID- 9019686
TI  - Nurse practitioners--where do they belong within the organizational structure of
      the acute care setting?

PMID- 9019687
TI  - Employer resistance to state authorized prescriptive authority for NPs: results
      from a pilot study.

PMID- 9019688
TI  - Employer resistance to state authorized prescriptive authority for NPs: results
      from a pilot study.

PMID- 9019689
TI  - Employer resistance to state authorized prescriptive authority for NPs: results
      from a pilot study.

PMID- 9019690
TI  - Justifying nurse practitioner existence: hard facts to hard figures.
AB  - When lawmakers and insurers ask nurse practitioners how NPs differ from
      physicians and why they should be incorporated into patient care systems, NPs
      answer that they are better listeners, pay more attention to prevention, and that
      they give safe care and have a high level of patient satisfaction. Lawmakers and
      insurers are not always impressed with this type of answer. These policy makers
      may understand that NPs do some of the same things as physicians, but they do not
      always understand why anyone should seek out NPs when physicians are available.
      This article outlines the types of data needed to support NP practice before
      lawmakers, bureaucrats, and business-people. The article examines impressive
      facts and figures that are emerging and suggests what is needed in the way of
      further data collection and continuing advancement of the profession.

PMID- 9019691
TI  - Asymptomatic bacteriuria in older adults: when is it necessary to screen and
      treat?
AB  - The incidence of asymptomatic bacteriuria increases with age, and thus it is a
      common finding in older adults, especially the very old and the
      institutionalized. Bacteriuria in most older adults, while common, is often
      transient. The clinical significance is generally minor and the treatment yields
      very little benefit, is expensive, and may cause substantial drug toxicity.
      Guidelines to help determine which patients may benefit from treatment are
      included. Primary care providers for older adults in ambulatory, home, hospital,
      or institutional settings, should recognize asymptomatic bacteriuria and know
      when and when not to treat. This management decision will become an increasingly
      important aspect of gerontological health care.

PMID- 9019692
TI  - The early and periodic screening, diagnosis and treatment program: opportunities
      for nurse practitioners.
AB  - The Early and Periodic Screening, Diagnosis and Treatment (EPSDT) Program is
      intended to provide comprehensive preventive health care services for children
      and young adults from low-income families on Medicaid. Unfortunately, only a
      fraction of the individuals eligible for care actually receive EPSDT services,
      often because of a shortage of providers who offer these services. Nurse
      practitioners are ideally suited to offer such services and, in states where they
      are allowed to function independently, can receive direct Medicaid reimbursement
      for them. Because many nurse practitioners are unfamiliar with the EPSDT program,
      this article describes the key components of the program and explains how nurse
      practitioners can provide EPSDT services.

PMID- 9019693
TI  - Noncompliance in adolescent oral contraceptive users.

PMID- 9019694
TI  - The primary care management of burns.
AB  - In 1993, there were 2.2 million burns per year, with approximately 60,000 burn
      victims needing hospitalization. Burns are a major cause of traumatic injury in
      all ages of the population. No matter the cause, the basic pathophysiology of all
      burns is similar. It is essential for primary care providers to understand the
      physiologic alterations that occur with burns and to have a complete knowledge of
      the assessment and treatment of burns. Patient outcome is directly related to
      initial stabilization and resuscitation. The article discusses history taking and
      care of the burn patient at the site and the tools used for an accurate
      assessment of the burn. Thorough assessment is needed before management plans can
      be instituted. Risks associated with burns and recommendations for management of
      patients, including using the Parkland formula for fluid resuscitation, are also
      presented. A quarter of a million burns can be treated adequately on an
      outpatient basis.

PMID- 9019695
TI  - Plasma glucose screening of adults.

PMID- 9019696
TI  - Mild cognitive impairment in HIV disease.

PMID- 9019697
TI  - Combined endodontic-periodontal lesion of developmental origin: a case report.

PMID- 9019698
TI  - 99Tcm-sestamibi uptake by malignant melanoma lesions.

PMID- 9019699
TI  - [A new, more invasive approach in the radiation diagnosis of breast cancer].
AB  - The authors discuss the state-of-the-art techniques and the increasingly invasive
      approach to the diagnosis of breast diseases and also summarise their own
      experiences. Special attention is called to the nonpalpable, preclinical stage of
      breast cancers. The newest techniques like MR-mammography, stereo-taxic and
      ultrasound directed cytology and core biopsy are demonstrated, as well as the
      present place of traditional breast imaging methods: mammography and diagnostic
      ultrasound. The preoperative localisation of nonpalpable cancers improves the
      safety of surgical procedures. The authors emphasize the importance of the
      detection of early breast cancer, for the sake of a more favourable prognosis
      compared to that of the palpable, advanced cases. The results of mass screening
      is detailed, based on statistical data.

PMID- 9019700
TI  - [Serologic signs of Epstein-Barr-virus infections in various patients without
      infectious mononucleosis].
AB  - The authors detected Epstein-Barr virus (EBV) virus capsid (VCA) antibodies of
      IgM and IgG type together with EBNA and heterophil antibodies in the sera
      collected from 1882 unselected patients without infectious mononucleosis. Out of
      them IgM type antibodies were found in 123 cases and in an additional group of 30
      patients heterophil antibodies were detected together with EBV specific virus
      markers. Altogether 153 patients were considered as cases of primary EBV
      infection, or reinfection. Comparing the distribution of age groups of the 1729
      and the 153 patients, the author observed the increased incidence of elderly
      cases among patients with actual EBV infection, particularly above 60 years of
      age (P < 0.001). The 1729 patients were composed of 141 main diagnostic groups
      and the 153 patients with actual EBV infection consisted of 30 main diagnostic
      groups of which more than one third (53 cases) were of alcoholic liver diseases
      and patients of HBsAg carriers. The authors suppose, that in the cases of
      alcoholic liver diseases and of HBsAg carriers the suspected "immunocompromised"
      condition of those patients resulted the actual EBV infection, or reinfection. In
      other cases, like virus infection or meningitis serosa, it is suspected that the
      EBV can be responsible producing the symptoms.

PMID- 9019701
TI  - [Prognostic role of cisteine and serin proteases in gastriC cancer].
AB  - Cysteine proteases (cathepsin B and L), the serine protease urokinase-type
      plasminogen activator and its inhibitor type-1 play an important part in cancer
      invasion and metastasis. The authors determined the protease concentrations in
      gastric cancer tissues, using the ELISA method, in patients with gastric cancer.
      They evaluated the prognostic role of proteases and the relationship that these
      proteases may have with other histomorphological prognostic parameters such as
      tumor staging, grading, histotype, Borrmann classification. The Cox survival
      analysis showed that cathepsin B (p = 0.002), urokinase-type plasminogen
      activator (p = 0.0001) and the inhibitor type-1 (p = 0.0004) significantly
      correlated with poor prognosis. The tumor staging, grading, Borrmann
      classification correlated also significantly with survival time. Urokinase-type
      plasminogen activator was selected as the single independent variable in the Cox
      model (p = 0.0001).

PMID- 9019702
TI  - [Joint hypermobility: frequent cause of low back pain].
AB  - This paper is concerned with vertebral hypermobility that is often associated
      with low back pain. This is not uncommon the hungarian general population. The
      diagnosis of this condition is essentially clinical. The treatment is special
      physiotherapy and to learn how to avoid unaesthetic postures through appropriate
      muscular control. It is important to recognize this syndrome, since a firm
      diagnosis and reassurance may help the patient considerably and save a great deal
      of anxiety, medicine, time and money to the patient and to the National Health
      Service as well.

PMID- 9019703
TI  - [Simultaneous occurrence and treatment of right atrial myxoma and extensive
      colonic polyposis causing recurrent intestinal hemorrhages].
AB  - The authors describe the case history of 68 year old man. Right atrial myxoma had
      been diagnosed two years prior to this present observation, however surgical
      intervention has been contraindicated due to high operative risk. Later the
      patient was referred to a cardiological evaluation because of chronic atrial
      fibrillation before a cataract surgery in a symptom free condition. The right
      atrial myxoma caused inflow obstruction and tricuspid regurgitation was removed
      before the eye surgery. In addition, tricuspid valve replacement and
      revascularization of three coronary arteries has been performed. The patient
      receiving chronic anticoagulant therapy experienced severe gastrointestinal
      bleeding the source of which turned out to be a partially malignant colon
      polyposis. The polyps were successfully removed by coloscopy and intra operative
      coloscopy. No gastrointestinal bleeding has been observed afterwards in spite of
      the continued anticoagulation. After review of the literature the authors
      observed that according to their knowledge the common occurrence of the right
      atrial myxoma and the colon polyposis had not been described before.

PMID- 9019704
TI  - [Letters by Laszlo Nemeth on aging].

PMID- 9019705
TI  - [Remembering the "most Hungarian of Hungarians": Ferenc Flor].

PMID- 9019706
TI  - [Problems the BCG vaccination].

PMID- 9019707
TI  - [Problems with the BCG vaccination].

PMID- 9019708
TI  - [The first heart suturing was performed in 1896, not 1897].

PMID- 9019709
TI  - Spontaneous tension oscillation in skinned bovine cardiac muscle.
AB  - Skinned fibres from bovine ventricles exhibited spontaneous tension oscillations
      when MgADP and inorganic phosphate (Pi) were added to the solution bathing fibres
      in the relaxed state (ADP-SPOC). A similar type of oscillation was observed at
      intermediate concentrations of free Ca2+ in the absence of MgADP and Pi (Ca
      SPOC). To investigate the correlation between ADP-SPOC and Ca-SPOC, we
      constructed two-dimensional state diagrams of cardiac muscle using different
      concentrations of Pi (0-20 mM) and free Ca2+ [pCa=around 5 (+Ca2+), pCa=5.15-6.9
      and +EGTA (-Ca2+)], with varying concentrations of MgADP (0-10 mM), with 2 mM
      MgATP and 2 mM free Mg2+ maintaining ionic strength at 0.15+/-0.01 M, pH 7.0, 25
      degrees C. The three-dimensional (pCa-Pi-MgADP) state diagram thus obtained was
      divided into three regions, i.e. the contraction region in which tension
      oscillation was undetectable, the spontaneous tension oscillation (SPOC) region
      and the relaxation region. We found that the regions of ADP-SPOC and Ca-SPOC were
      continuously connected by a single oscillation region sandwiched between the
      contraction and relaxation regions. The state diagram, which encompasses
      physiological conditions, shows that the probability of SPOC is higher in cardiac
      muscle than in skeletal muscle. From these results, we suggest that, despite
      distinct ionic conditions, the molecular state of cross-bridges during SPOC is
      common to both ADP-SPOC and Ca-SPOC.

PMID- 9019710
TI  - Vasopressin-stimulated Ca2+ reabsorption in rabbit cortical collecting system:
      effects on cAMP and cytosolic Ca2+.
AB  - The effect of arginine vasopressin (AVP) on transepithelial Ca2+ transport in
      primary cultures of rabbit cortical collecting system cells was examined.
      Addition of AVP to the basolateral side of the monolayer dose-dependently (EC50 =
      0.7 nM) increased active Ca2+ reabsorption from a basal value of 85 +/- 2 nmol.h
      1.cm-2 to a maximum value of 124 +/- 3 nmol.h-1.cm-2. This was paralleled by a
      dose-dependent (EC50 = 1.1 nM) increase in cellular adenosine 3', 5'-cyclic
      monophosphate (cAMP) content. Both effects of AVP were mimicked by the V2 agonist
      deamino-Cys,D-Arg8-vasopressin (dDAVP) and forskolin. Addition of either AVP or
      dDAVP to the basolateral side evoked a sustained increase in cytosolic free Ca2+
      concentration, which resulted from both Ca2+ entry and release from internal
      stores. Only the effect on Ca2+ entry was mimicked by forskolin, demonstrating
      that cAMP acts by activating a Ca2+ influx pathway. The present findings
      demonstrate that AVP stimulates transcellular Ca2+ transport in the cortical
      collecting system through activation of basolateral V2 receptors coupled to
      adenylyl cyclase to increase the cellular cAMP content.

PMID- 9019711
TI  - Absence of acetylcholine- and ionomycin-activated Cl- currents in submandibular
      cells of early postnatal rats.
AB  - Using the whole-cell patch-clamp technique, we investigated developmental changes
      in the expression of an acetylcholine- (Ach-) activated Cl- conductance in rat
      submandibular acinar cells. ACh induced an oscillatory inward current in cells
      isolated from animals older than 5 weeks, but not in animals less than 2-3 weeks
      of age. The current/voltage (I/V) relationship of the ACh-induced current was
      that of an outward rectifier, and the current was inhibited by intracellular
      BAPTA, a Ca2+ buffer, indicating the current was Ca2+ activated. The ACh-induced
      current was also blocked in the presence of DPC and SITS, two Cl- current
      inhibitors in other tissues. Ionomycin mimicked the effect of ACh but in a
      nonoscillatory fashion. The appearance of the ionomycin-induced currents was also
      age related, as the current was not observed to occur in animals less than 2-3
      weeks old. Since both ACh and ionomycin significantly increase cytosolic [Ca2+]
      in the acinar cells of young animals, the correlation between the age dependence
      of the ACh-activated Cl- current and the ionomycin-activated Cl- current
      responses suggests that the lack of responsiveness observed in the young animals
      is due to the absence of Ca2+-activated Cl- channels, rather than to a deficiency
      of a cellular mediator.

PMID- 9019712
TI  - The regulation of type-I collagen synthesis by insulin-like growth factor-I in
      human osteoblast-like SaOS-2 cells.
AB  - The effect of insulin-like growth factor-I on collagen synthesis was studied
      using cultured human osteoblast-like SaOS-2 cells by measuring the incorporation
      of tritiated L-proline into immunoprecipitable type-I collagen. Tritiated L
      proline incorporation into collagen was significantly stimulated by insulin-like
      growth factor-I in a time- and concentration-dependent manner. Unlabelled L
      proline and alpha-(methylamino) isobutyric acid inhibited either the influx into
      cells, or the incorporation into collagen, of tritiated L-proline. The increase
      in incorporation of tritiated L-proline was significantly reduced by
      cycloheximide and actinomycin D. L-Proline incorporation into collagen was also
      stimulated by insulin-like growth factor-II, insulin-like growth factor-I
      analogues and insulin. The insulin-like growth factor-I-stimulated L-proline
      incorporation was inhibited by one of its binding proteins, insulin-like growth
      factor binding protein-4, in a concentration-dependent manner.

PMID- 9019713
TI  - Hypoxic inhibition of K+ currents in isolated rat type I carotid body cells:
      evidence against the involvement of cyclic nucleotides.
AB  - Whole-cell patch-clamp recordings were used to evaluate the effects of the cyclic
      nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'
      cyclic monophosphate (cGMP) on ionic currents in type I carotid body cells
      isolated from rat pups, and to investigate whether cyclic nucleotides are
      involved in K+ current inhibition by hypoxia. In the presence of 500 microM
      isobutylmethylxanthine, currents were not significantly modified by 8-bromo-cAMP
      (2 mM), dibutyryl-cAMP (5 mM) or 8-bromo-cGMP (2 mM). Currents were also
      unaffected by the phosphodiesterase (PDE)-resistant protein kinase A activators
      Sp-cyclic adenosine-3', 5'-monophosphorothioate (Sp-cAMPS) and Sp-8
      bromoadenosine-3', 5'-monophosphorothioate (Sp-8-bromo-cAMPS) (50 microM), or by
      beta-phenyl-1,N2-ethenoguanosine-3',5'-cyclic monophosphate (PET-cGMP) (100
      microM) or the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP; 500
      microM). Ca2+ channel currents were also unaffected by Sp-8-Br-cAMPS, PET-cGMP
      and SNAP at the same concentrations. In the absence of cyclic nucleotide
      analogues, hypoxia (PO2 17-23 mmHg) reversibly inhibited K+ currents. This degree
      of hypoxic inhibition was not significantly altered by the PDE-resistant protein
      kinase A inhibitors Rp-cyclic adenosine-3', 5'-monophosphorothioate (Rp-cAMPS)
      (50 microM) or Rp-8-bromoadenosine-3',5'-monophosphorothioate (Rp-8-bromo-cAMPS)
      (200 microM). Similarly, PET-cGMP (100 microM) and SNAP (500 microM) did not
      alter the degree of inhibition caused by hypoxia. At the same concentrations used
      in type I cell experiments, Sp-8-bromo-cAMPS, PET-cGMP and SNAP completely
      relaxed isolated guinea-pig basilar arteries preconstricted with 20 mM K+
      containing solutions. Our results indicate that cyclic nucleotides alone are not
      an important factor in the regulation by O2 tension of K+ currents in rat type I
      carotid body cells.

PMID- 9019714
TI  - AVP-independent high osmotic water permeability of frog urinary bladder and
      autacoids.
AB  - In the isolated frog urinary bladder a 20- to 50-fold increase of the osmotic
      water permeability has been revealed in the absence of arginine vasopressin (AVP)
      as a result of several successive changes of the serosal Ringer solution. This
      increase of the osmotic water permeability was of the same magnitude as that of
      the effect of 1 nM AVP. Similarly to the effect of AVP, the amount of adenosine
      3',5'-cyclic monophosphate (cAMP) in the cells rose, and aggregates of
      intramembraneous particles were formed in the apical plasma membrane of granular
      cells (as shown by the freeze-fracture method). Immunocytochemical studies using
      anti-actin monoclonal antibodies indicated depolymerization of F-actin following
      the AVP-independent change in water permeability. It was possible to decrease the
      high level of osmotic permeability to the initial level if 10 microl/ml of frog
      blood serum or a lipid extract of this blood serum, or 1 microM arachidonic acid
      or 1 nM prostaglandin E2 was added to the serosal Ringer solution. The rapid
      restoration of the osmotic water impermeability of the epithelium after the AVP-
      evoked effect was achieved by the addition to the serosal Ringer solution of
      Ringer solution in which intact frog urinary bladders had been previously
      incubated for 1 h. The data obtained indicate that the maintenance of the
      impermeability to water of the osmoregulating epithelium and the restoration of
      the initial low level of the osmotic permeability after the effect of AVP are due
      to participation of prostaglandin E2 and other autacoids as well as, probably,
      some physiologically active substances of a lipid nature that are present in the
      blood serum.

PMID- 9019715
TI  - The role of mitochondria-rich cells in sodium transport across amphibian skin.
AB  - The possible participation of mitochondria-rich cells in transepithelial Na+
      transport across frog skin under "physiological conditions" (low apical [Na+],
      open circuited) was analysed by recording electrophysiological parameters from
      principal cells with intracellular microelectrodes and using measurement of Rb+
      uptake into the epithelial cells from the serosal side via the Na+/K+-ATPase. It
      was observed that transport perturbation with amiloride induced changes in the
      apical potential difference and fractional apical resistance in principal cells,
      observations which are compatible with the notion that the essential fraction of
      transcellular current flow occurs across these cells. Amiloride-inhibitable
      uptake of Rb+ was also restricted to principal cells, the amount being about
      equivalent to the predicted rate of K+ recycling via the Na+/K+-ATPase. The
      results indicate that principal cells are responsible for transepithelial Na+
      transport irrespective of the experimental conditions. Flow of Na+ across
      mitochondria-rich cells appears to be negligible.

PMID- 9019716
TI  - The effects of the level of activation and shortening velocity on energy output
      in type 3 muscle fibres from Xenopus laevis.
AB  - We investigated the effect of shortening velocity on the efficiency of single
      intact slow-twitch muscle fibres (type 3) of Xenopus laevis, at different levels
      of activation (10, 15, 20 and 40 Hz). Fused contractions were obtained at 40 Hz
      stimulation. When maximal isometric force had been reached, the fibres were
      shortened by 10% of the fibre length (L0) at 0.4, 1 and 2 L0/s. To investigate
      whether the oscillating force at low stimulation frequencies influenced power
      output and the rate of heat production, we also performed these experiments with
      the fibre bathed in dantrolene. The results with fused contractions in the
      presence of dantrolene were the same as with unfused contractions. At 40 Hz
      stimulation during shortening the rate of heat production increased above that
      measured during isometric contractions, while at the lower stimulation
      frequencies the rate of heat production was less than that during isometric
      contractions. Mechanical efficiency was highest at low activation, and increased
      more with shortening velocity than at high activation. The actomyosin efficiency
      (i.e. the efficiency corrected for "activation heat") was also highest at 10 Hz
      stimulation. We conclude that in slow-twitch muscle fibres of X. laevis, near the
      optimum shortening velocity, cross-bridge efficiency is highest for partially
      activated muscle.

PMID- 9019717
TI  - An increase in [Ca2+]i activates basolateral chloride channels and inhibits
      apical sodium channels in frog skin epithelium.
AB  - The aim of this study was to investigate the mechanisms by which increases in
      free cytosolic calcium ([Ca2+]i) cause a decrease in macroscopic sodium
      absorption across principal cells of the frog skin epithelium. [Ca2+]i was
      measured with fura-2 in an epifluorescence microscope set-up, sodium absorption
      was measured by the voltage-clamp technique and cellular potential was measured
      using microelectrodes. The endoplasmic reticulum calcium-ATPase inhibitor
      thapsigargin (0.4 microM) increased [Ca2+]i from 66 +/- 9 to 137 +/- 19 nM (n =
      13, P = 0.002). Thapsigargin caused the amiloride-sensitive short circuit current
      (Isc) to drop from 26.4 to 10.6 microA cm-2 (n = 19, P<0.001) concomitant with a
      depolarization of the cells from -79 +/- 1 to -31 +/- 2 mV (n = 18, P<0.001).
      Apical sodium permeability (PaNa) was estimated from the current/voltage (I/V)
      relationship between amiloride-sensitive current and the potential across the
      apical membrane. PaNa decreased from 8.01.10(-7 )to 3.74.10(-7) cm s-1 (n = 7, P
      = 0.04) following an increase in [Ca2+]i. A decrease in apical sodium
      permeability per se would tend to decrease Isc and result in a hyperpolarization
      of the cell potential and not, as observed, a depolarization. Serosal addition of
      the chloride channel inhibitors 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic
      acid (DIDS), diphenylamine-2-carboxylate (DPC), indanyloxyacetic acid 94 (IAA-94)
      and furosemide reversed the depolarization induced by thapsigargin, indicating
      that chloride channels were activated by the increase in [Ca2+]i. This was
      confirmed in wash-out experiments with 36Cl where it was shown that thapsigargin
      increased the efflux of chloride from 32.49 +/- 5.01 to 62.63 +/- 13.3 nmol.min-1
      cm-2 (n = 5, P = 0.04). We conclude that a small increase in [Ca2+]i activates a
      chloride permeability and inhibits the apical sodium permeability. The activation
      of chloride channels and the closure of apical sodium channels will tend to lower
      the macroscopic sodium absorption.

PMID- 9019718
TI  - Excitatory sodium currents of NH15-CA2 neuroblastoma x glioma hybrid cells are
      differently affected by interleukin-2 and interleukin-1beta.
AB  - The neuroblastoma x glioma hybrid cell line NH15-CA2 was used to test the effects
      of two interleukins on neuronal Na+ channels. The cells were cultured in the
      presence of dibutyryl cAMP and retinoic acid, which yielded a high expression of
      Na+ channels so that the cells were excitable. Na+ currents were triggered and
      recorded in the whole-cell recording mode. Comparison of the effects of
      tetrodotoxin and mu-conotoxin established that the expressed Na+ channels were of
      the neuronal type. Bath-applied recombinant human interleukin-2 (rIL-2) had a
      reversible inhibitory effect on the Na+ currents, although to a lesser extent
      than on muscular Na+ currents (more than 1000 U/ml required for 50% block in NH15
      CA2 cells vs 500 U/ml in myoballs). The current/voltage relationship was not
      affected by the presence of rIL-2, but the steady-state inactivation curve was
      shifted by -7.7 +/- 4.8 mV (mean +/- SD, n=18). Recombinant human interleukin
      1beta (rIL-1beta), applied at 1000 U/ml, showed an inhibitory effect on the Na+
      currents in about one-third of the cells tested. The mechanism of inhibition was
      different from that of rIL-2, as rIL-1beta seemed to cause a block without
      affecting voltage dependence or kinetics of the channels.

PMID- 9019719
TI  - Blood flow occlusion, maximal force production and EMG in two rat gastrocnemius
      muscle compartments.
AB  - The proximal and distal compartments of rat medial gastrocnemius muscle are
      dominated, respectively by, fast-twitch oxidative and fast twitch glycolytic
      fibres. In the present study it was hypothesized that repetitive in situ
      activation with an intact blood supply would cause greater declines in maximal
      tetanic force, compound action potential (CAP) amplitude and CAP area in the
      distal compared to the proximal compartment. Furthermore, it was hypothesized
      that these differences would be eliminated after occlusion of the blood supply to
      the muscle. A twitch followed by a tetanus (120 Hz, 200 ms duration) was given
      every 3 s for 2 min. This exercise protocol was applied once with, and once
      without, blood supply. During the first minute of the exercise, as expected,
      occlusion enhanced the decline of proximal force to 77.4 +/- 0.8%, a level
      comparable (P>0.05) to the decline of distal force (79.7 +/- 1. 2%). In contrast
      with the hypothesis, CAP amplitude was not significantly affected by occlusion
      and it changed significantly less in the proximal (to 102.9 +/- 4.5%) compared to
      the distal (to 69.0 +/- 6.7%) compartment. During the second minute of activation
      without blood flow, sudden declines of distal CAP amplitude (to 18.4 +/- 3.4%)
      coupled with parallel declines in force (to 17.6 +/- 2.8%) were observed to occur
      in the distal but not in the proximal compartment. Proximal final force and CAP
      amplitude were 54.2 +/- 2. 6% and 80.6 +/- 5.9% respectively. Thus, in contrast
      with the hypothesis, occlusion enhanced the differences between compartments.
      These results are discussed in relation to fibre type composition and metabolic
      changes. It is suggested that a loss of force caused by a decreased muscle fibre
      excitability upon repetitive activation depends not only on fibre type, but also
      on the intramuscular location of the fibres.

PMID- 9019720
TI  - Comparison of parzen density and frequency histogram as estimators of probability
      density functions.
AB  - In neurobiology, and in other fields, the frequency histogram is a traditional
      tool for determining the probability density function (pdf) of random processes,
      although other methods have been shown to be more efficient as their estimators.
      In this study, the frequency histogram is compared with the Parzen density
      estimator, a method that consists of convolving each measurement with a weighting
      function of choice (Gaussian, rectangular, etc) and using their sum as an
      estimate of the pdf of the random process. The difference in their performance in
      evaluating two types of pdfs that occur commonly in quantal analysis (monomodal
      and multimodal with equidistant peaks) is demonstrated numerically by using the
      integrated square error criterion and assuming a knowledge of the "true" pdf. The
      error of the Parzen density estimates decreases faster as a function of the
      number of observations than that of the frequency histogram, indicating that they
      are asymptotically more efficient. A variety of "reasonable" weighting functions
      can provide similarly efficient Parzen density estimates, but their efficiency
      greatly depends on their width. The optimal widths determined using the
      integrated square error criterion, the harmonic analysis (applicable only to
      multimodal pdfs with equidistant peaks), and the "test graphs" (the graphs of the
      second derivatives of the Parzen density estimates that do not assume a knowledge
      of the "true" pdf, but depend on the distinction between the "essential features"
      of the pdf and the "random fluctuations") were compared and found to be similar.

PMID- 9019721
TI  - [Ca2+]i elevation evoked by Ca2+ readdition to the medium after agonist-induced
      Ca2+ release can involve both IP3-, and ryanodine-sensitive Ca2+ release.
AB  - Sustained Ca2+ elevation ("Ca2+ response"), caused by subsequent readdition of
      Ca2+ to the medium after application of adenosine 5'-triphosphate (ATP, 15
      microM) in a Ca2+-free medium, was studied using single bovine aortic endothelial
      (BAE) cells. In cells in which the resting intracellular Ca2+ concentration
      ([Ca2+]i) was between about 50 and 110 nM, a massive Ca2+ response occurred and
      consisted of phasic and sustained components, whereas cells with a resting
      [Ca2+]i of over 110 nM displayed small plateau-like Ca2+ responses. An increase
      of internal store depletion resulted in loss of the phasic component. When the
      store was partly depleted, the dependence of the Ca2+ response amplitude on
      resting [Ca2+]i was biphasic over the range of 50 to 110 nM. The greatest degree
      of store depletion was associated with small monophasic Ca2+ responses, the
      amplitudes of which were almost constant and in the same range as resting
      [Ca2+]i. Ni2+, known to partly block Ca2+ entry, caused no change in the half
      decay time of [Ca2+]i down to the level of the sustained phase [57 +/- 4 s in
      control and 54 +/- 3 s (n = 13) in the presence of 10 mM Ni2+] when added at the
      peak of the phasic component of the Ca2+ response. However, it lowered the
      sustained phase of the Ca2+ response by 42%. When applied at the start of the
      readdition of Ca2+, Ni2+ blocked the phasic component of the Ca2+ response, there
      being a threefold decrease in the initial rate of [Ca2+]i rise. In cells with a
      resting [Ca2+]i of 75-80 nM, pre-treatment with ryanodine (10 microM) did not
      affect the peak amplitude of the Ca2+ response, but it did increase the level of
      the sustained component. In some cells, ryanodine caused an oscillatory Ca2+
      response. In conclusion, partial depletion of the inositol 1,4, 5-trisphosphate
      (IP3-) sensitive store by a submaximal concentration of agonist (in Ca2+-free
      medium) was followed, on readdition of Ca2+, by Ca2+ entry, which appeared to
      trigger IP3-sensitive Ca2+ release (IICR) which, in turn, initiated Ca2+
      sensitive Ca2+ release (CICR), thus resulting in a massive elevation of [Ca2+]i.

PMID- 9019722
TI  - Neomycin inhibits K+-induced force and Ca2+ channel current in rat arterial
      smooth muscle.
AB  - The techniques of small vessel isometric myography and patch clamp were used to
      investigate the action of neomycin on K+-induced isometric force and voltage
      gated Ca2+ channel currents in rat arterial smooth muscle. Neomycin and the
      dihydropyridine (DHP) Ca2+ channel antagonist (-)202-791 concentration
      dependently and reversibly inhibited 40 mM K+-induced isometric force in rings of
      rat mesenteric and basilar arteries (IC50 values of 70 microM and 1. 2 nM,
      respectively, n = 10 and 4). Elevation of [Ca2+]o by a factor of 2 significantly
      reduced the IC50 values for inhibition of K+-induced force for both neomycin and
      (-)202-791 (192 microM and 3. 7 nM, respectively, n = 6 and 4), but did not
      affect the Hill coefficient of the concentration/effect relationships. In patch
      clamp experiments using freshly isolated basilar arterial myocytes, the voltage
      gated inward current carried by Ba2+ was reversibly and concentration-dependently
      inhibited by neomycin (IC50 32 microM, n = 3). The concentration/effect curve for
      inhibition of the inward Ba2+ current by neomycin was significantly shifted to
      the right when [Ba2+]o was raised from 1.8 mM to 10 mM (IC50 144 microM, n = 8).
      Our findings suggest that neomycin relaxes high-K+-induced force in rat isolated
      mesenteric and basilar arteries largely by inhibition of voltage-dependent and
      DHP-sensitive Ca2+ channels.

PMID- 9019723
TI  - Confocal microscopic detection of potential-sensitive dyes used to reveal loss of
      voltage control during patch-clamp experiments.
AB  - We used a fast, fluorescent, potential-sensitive indicator (Di-8-ANEPPS) in
      combination with laser-scanning confocal microscopy in the line-scan mode
      (temporal resolution 500 Hz) to independently determine the transmembrane
      potential in voltage-clamped cells. While a linear relation between command
      voltage and Di-8-ANEPPS fluorescence was found in unexcitable Sf9 cells,
      pronounced nonlinearities were observed in cardiac myocytes. Comparison of the
      fluorescence records and current traces indicated that most of the observed
      nonlinearities could be attributed to voltage-escape during flow of membrane
      current. Voltage-escape during large membrane currents may lead to various
      experimental difficulties during voltage-clamp experiments. The voltage recording
      technique based on fluorescence was then used to compare the voltage-escape
      during flow of Na+ and Li+ ions via voltage-dependent (TTX sensitive) Na+
      channels in cardiac myocytes. In these experiments, no significant differences in
      the degree of voltage-escape was found, suggesting that the two currents were
      similar in amplitude. In addition to the application presented in this paper,
      confocal microscopic detection of transmembrane potential with fluorescent dyes
      may be a useful technique for experiments in preparations that are difficult to
      impale with microelectrodes because of their small size.

PMID- 9019724
TI  - A new technique for assessing the microscopic distribution of cellular calcium
      exit sites.
AB  - This paper contains a description of a new method designed to monitor the
      distribution of Ca2+ efflux from cells or small cellular aggregates. The idea
      behind this method is to use a fluorescent Ca2+ indicator bound to dextrans of
      high molecular weight to slow down Ca2+ diffusion. Due to the decrease in
      diffusion rate, Ca2+ ions should be held close to the site of their release from
      the cells for a relatively long time, enough for the confocal microscope to
      detect such a local increase in Ca2+ concentration. This paper gives a detailed
      description of the method, illustrated with results of measurements of agonist
      dependent and agonist-independent Ca2+ extrusion from pancreatic acinar cells. An
      appendix provides the mathematical background that should allow selection of the
      concentration of buffer which is necessary to achieve a particular Ca2+ diffusion
      coefficient.

PMID- 9019725
TI  - Monovalent cation conductance of the sustained inward current in rabbit
      sinoatrial node cells.
AB  - Under the whole cell clamp, superfusion of the rabbit sinoatrial node cells with
      a Na+-free solution suppressed the sustained inward current (Ist), and the L-type
      Ca2+ current (ICa,L) could be recorded on depolarization less negative than -40
      mV from the holding potential of -80 mV. On the other hand, replacement of Ca2+
      with Mg2+ in the external solution suppressed inward-going ICa,L and isolated
      Ist. Under this condition, Ist measured as a nicardipine-sensitive current showed
      an activation threshold between -60 and -70 mV. The conductance sequence of Ist
      for monovalent ions was determined as Na+ > Li+ >> K+ approximately = Cs+ by
      replacing the external Na+ with these alkali metal ions. The contribution of Ist
      to the diastolic depolarization is discussed.

PMID- 9019726
TI  - Differences in alpha2-adrenoceptor modulation of calcium channels in vascular
      smooth muscle cells of male and female rats.
AB  - Effects of the alpha2-adrenergic agonist clonidine on current through Ca2+
      channels was recorded from vascular smooth muscle cells isolated from tail
      arteries and aortae of male and female rats. The average Ba2+ current in control
      was not significantly different between males and females; however, clonidine (1
      microM) enhanced Ba2+ current through Ca2+ channels in cells from females, but
      not from males. The greater sensitivity of vascular smooth muscle cells to
      clonidine may underlie different contractile responses to alpha2-adrenergic
      agonists between males and females.

PMID- 9019727
TI  - Effects of the Na+/H+-exchange inhibitor Hoe 642 on intracellular pH, calcium and
      sodium in isolated rat ventricular myocytes.
AB  - The inhibitors of the Na+/H+-exchange (NHE1) system Hoe 694 and Hoe 642 possess
      cardioprotective effects in ischaemia/reperfusion. It is assumed that these
      effects are due to the prevention of intracellular sodium (Nai) and calcium (Cai)
      overload. The purpose of the present study was to investigate the effects of Hoe
      642 on intracellular pH, Na+ and Ca2+ (pHi, Nai and Cai) in isolated rat
      ventricular myocytes under anoxic conditions or in cells in which oxidative
      phosphorylation had been inhibited by 1.5 mmol/l cyanide. In cells which were
      dually loaded with the fluorescent dyes 2, 7-biscarboxyethyl-5,6
      carboxyfluorescein (BCECF) and Fura-2, anoxia caused acidification of the cells
      (from pHi 7.2 to pHi 6.8) and an increase in Cai from about 50 nmol/l to about 1
      micromol/l. The decrease in pHi began before the cells underwent hypoxic (rigor)
      contracture, whereas Cai only began to rise after rigor shortening had taken
      place. After reoxygenation, pHi returned to its control value and Cai oscillated
      and then declined to resting levels. It was during this phase that the cells
      rounded up (hypercontracture). When 10 micromol/l Hoe 642 was present from the
      beginning of the experiment, pHi and Cai were not significantly different from
      control experiments. At reoxygenation, pHi did not recover, but Cai oscillated
      and returned to its resting level. To monitor Nai, the cells were loaded with the
      dye SBFI. After adding 1.5 mmol/l cyanide or 100 micromol/l ouabain, Nai
      increased from the initial 8 mmol/l to approximately 16 mmol/l. Hoe 642 or Hoe
      694 (10 micromol/l) did not prevent the increase in Nai. In contrast, the blocker
      of the persistent Na+ current R56865 (10 micromol/l) attenuated the CN--induced
      rise in Nai. The substance ethylisopropylamiloride was not used because it
      augmented considerably the intensity of the 380 nm wavelength of the cell's
      autofluorescence. In conclusion, the specific NHE1 inhibitor Hoe 642 did not
      attenuate anoxia-induced Cai overload, nor CN--induced Nai and Cai overload. Hoe
      642 prevented the recovery of pHi from anoxic acidification. This low pHi
      maintained after reoxygenation may be cardioprotective. Other possible mechanisms
      of NHE1 inhibitors, such as prevention of Ca2+ overload in mitochondria, cannot
      be ruled out. The increase in Nai during anoxia is possibly due to an influx of
      Na+ via persistent Na+ channels.

PMID- 9019728
TI  - Role of G-proteins in the regulation of organic osmolyte efflux from isolated rat
      renal inner medullary collecting duct cells.
AB  - Hypotonic shock (change of osmolality from 600 mosmol to 300 mosmol by lowering
      NaCl concentration) increases the release of organic osmolytes from isolated
      inner medullary collecting duct (IMCD) cells in the following sequence: taurine >
      betaine > sorbitol > myo-inositol > glycerophosphorylcholine (GPC). The role of G
      proteins in regulating the hypotonicity-induced efflux was analysed by exposing
      cells to various concentrations of a G-protein inhibitor, pertussis toxin (PTX;
      20-200 ng/ml), and a Gialpha-protein stimulator, mastoparan (10-50 microM). PTX
      diminished the hypotonic release of sorbitol and betaine by 43.2+/-9. 5% and
      32.2+/-7.8% (n = 5), respectively. Efflux of GPC, myo-inositol and taurine was
      not significantly altered. Mastoparan (10 microM) increased osmolyte release
      under isotonic conditions such that release of betaine was increased 3.8-fold and
      that of sorbitol 2.1-fold, while GPC, myo-inositol and taurine effluxes were only
      slightly augmented. Under hypotonic conditions, mastoparan stimulated betaine
      release (1.86+/-0.2-fold, n = 5) but not that of sorbitol. As tested in
      connection with sorbitol and betaine release, the effect of mastoparan was
      abolished by PTX, but not the A23187-evoked sorbitol release. Like mastoparan,
      arachidonic acid increased the release of sorbitol and betaine under isotonic
      conditions, but under hypotonic conditions it only increased the release of
      betaine. As to the role of intracellular Ca2+, hypotonic shock evoked an
      intracellular Ca2+ peak which could be prevented by PTX. Mastoparan increased
      intracellular Ca2+ under isotonic conditions, whether the extracellular Ca2+
      concentration was low or high. The results indicate that G-proteins are involved
      in regulating sorbitol and betaine efflux from IMCD cells. The G-proteins
      regulating sorbitol release are probably involved in generating the proper
      intracellular Ca2+ signal. Betaine efflux, which is independent of intracellular
      Ca2+, might be regulated by a G-protein-stimulated release of arachidonic acid.
      Thus, probably several G-proteins are involved in controlling organic osmolyte
      efflux from IMCD cells.

PMID- 9019729
TI  - Regulation of force and shortening velocity by calcium and myosin phosphorylation
      in chemically skinned smooth muscle.
AB  - The phosphatase inhibitor okadaic acid (OA) was used to study the relationship
      between [Ca2+], rates of phosphorylation/dephosphorylation and the mechanical
      properties of smooth muscle fibres. Force/velocity relationships were determined
      with the isotonic quick release technique in chemically skinned guinea-pig taenia
      coli muscles at 22 degrees C. In the maximally thiophosphorylated muscle neither
      OA (10 microM) nor Ca2+ (increase from pCa 9.0 to pCa 4.5) influenced the force
      velocity relationship. When the degree of activation was altered by varying
      [Ca2+] in the presence of 0.5 microM calmodulin, both force and the maximal
      shortening velocity (Vmax) were altered. At pCa 5.75, at which force was about
      35% of the maximal at pCa 4.5, Vmax was 55% of the maximal value. When OA was
      introduced into fibres at pCa 6.0, force was increased from less than 5% to 100%
      of the maximal force obtained in pCa 4.5. The relationship between the degree of
      myosin light chain phosphorylation and force was similar in the two types of
      activation; varied [OA] at constant [Ca2+] and at varied [Ca2+]. The relation
      between force and Vmax when the degree of activation was altered with OA was
      almost identical to that obtained with varied [Ca2+]. The results show that Ca2+
      and OA do not influence force or Vmax in the maximally phosphorylated state and
      suggest that the level of myosin light chain phosphorylation is the major factor
      determining Vmax. The finding that the relationship between force and Vmax was
      similar when activation was altered with OA and Ca2+ suggests, however, that
      alterations in the absolute rates of phosphorylation and dephosphorylation at a
      constant phosphorylation level do not influence the mechanical properties of the
      skinned smooth muscle fibres.

PMID- 9019730
TI  - (-)-Baclofen-induced and constitutively active inwardly rectifying potassium
      conductances in cultured rat midbrain neurons.
AB  - Biophysical and pharmacological properties, and development of the (-)-baclofen
      induced potassium (KBac) conductance and the constitutively active inwardly
      rectifying potassium (KIR) conductance were characterised using the patch-clamp
      technique in cultured embryonic rat midbrain neurons. KBac conductance was
      induced by (-)-baclofen acting on gamma-aminobutyric acid B (GABAB) receptors,
      and displayed a high degree of selectivity for potassium ions, an approximate
      square-root dependence of conductance on extracellular potassium concentration
      and strongly voltage-dependent activation. Ba2+ blocked the conductance in a
      voltage-independent manner, whereas Cs+ produced a voltage-dependent block. In
      the same preparation, the KIR conductance displayed biophysical properties
      indistinguishable from those of the KBac conductance. Block of KIR currents by
      Ba2+ was voltage independent (KI, 4 microM), whereas Cs+ produced a voltage
      dependent block (KI, 370 microM at -100 mV, equivalent valence, z', 1.67). The
      KBac and KIR conductances additionally displayed a strikingly similar pattern of
      development in culture; the specific conductance (nS/pF) of both conductances
      increased two- to three-fold between the first and second week in vitro, and
      remained constant thereafter.

PMID- 9019731
TI  - Low-amiloride-affinity Na+ channel in the epithelial cells isolated from the
      endolymphatic sac of guinea-pigs.
AB  - By using the whole-cell patch-clamp technique, an amiloride-sensitive Na+
      selective conductance was found in epithelial cells from the endolymphatic sac
      (ES) epithelia of guinea-pigs. In the current-clamp configuration, the average
      resting membrane potential was -41.7+/-8.4 mV (n = 22). Application of amiloride
      at a concentration of 20 microM elicited a decrease in cation conductance that
      was responsible for a membrane hyperpolarization by 17.9+/-6.0 mV (n = 22).
      Substitution of N-methyl d-glucamine chloride (NMDG-Cl) for external NaCl led to
      a more significant membrane hyperpolarization by 28.4+/-8.3 mV (n = 22). At
      holding potential of -70 mV, amiloride and ethylisopropylamiloride (EIPA) blocked
      the inward current in a concentration-dependent manner over the range of
      concentrations of between 0.1 microM and 50 microM, with an inhibitory constant
      (Ki) of 1.3+/-0.4 microM (n = 7) and 1.5+/-0.3 microM (n = 5), respectively. In
      the voltage-clamp configuration, substitution of NMDG-Cl for external NaCl
      significantly reduced the inward current (n = 9), indicating that the whole-cell
      conductance has a high permeability for Na+. Superfusion with 20 microM amiloride
      induced a significant reduction of the inward current, shifted the reversal
      potential from -39.4+/-8.8 mV to -60.4+/-10.5 mV (n = 12), and decreased the
      inward conductance from 5.0+/-1.3 nS to 3.7+/-1.5 nS (n = 12). The permeability
      ratio of Na+ over K+, calculated from the difference in reversal potential
      between the currents before and after application of amiloride, was approximately
      5:1. Additionally, the conductance was not activated by application of forskolin,
      3-isobutyl-1-methylxanthine (IBMX) and 8-bromo-cAMP (8-Br-cAMP). These findings
      suggest that a low-amiloride-affinity Na+ channel localized in the ES epithelial
      cells may be involved in uptake of Na+ in the ES.

PMID- 9019732
TI  - Endothelial modulation of resting and stimulated vascular tone in the pig
      capsular testicular artery.
AB  - We have investigated the wall tension characteristics and the role of endothelium
      on vascular tone, at rest and under K+ depolarization, in isolated rings from the
      pig capsular testicular artery. The active tension reached a maximum that was
      significantly lower in vessels without endothelium, whereas the passive tension
      and the Ca2+-dependent myogenic tone were not significantly affected by
      endothelium removal. Both NG-nitro-l-arginine (L-NOARG, 10(-4) M) and methylene
      blue (10(-5) M), increased the basal resting tension (BRT) in vessels with
      endothelium, while indomethacin (10(-6) M) decreased BRT in vessels both with and
      without endothelium. Either removal of endothelium or treatment with indomethacin
      (10(-6) M), quinacrine (10(-5) M) or ibuprofen (10(-5) M), significantly
      depressed the K+ concentration response curve, while dazoxiben (10(-5) M) and SQ
      30,741 (10(-5) M) had no effect. L-NOARG (10(-6) M) potentiated the contractile
      response to K+ in vessels with endothelium, whereas L-NOARG (10(-4) M) was
      ineffective in vessels devoid of endothelium. These results suggest that a
      predominating NO release from endothelium, together with a cyclooxygenase-derived
      vasoconstrictor, modulate vascular tone at rest. In contrast, predominant
      endothelial release of a cyclooxygenase-derived contractile factor, but different
      from TXA2, PGH2 or superoxide anions, is induced by K+ depolarization and leads
      to vasoconstriction.

PMID- 9019733
TI  - Extracellular detection of K+ release during migration of transformed Madin-Darby
      canine kidney cells.
AB  - Madin Darby canine kidney cells transformed by alkaline stress (MDCK-F cells)
      constitutively migrate at a rate of about 1 microm.min-1. Migration depends on
      the intermittent activity of a Ca2+-stimulated, 53-pS K+ channel (KCa channel)
      that is inhibitable by charybdotoxin. In the present study we examined whether
      this intermittent KCa channel activity results in a significant K+ loss across
      the plasma membrane. K+ efflux from MDCK-F cells should result in a transient
      increase of extracellular K+ ([K+]e) in the close vicinity of a migrating cell.
      However, due to the rapid diffusion of K+ ions into the virtually infinite
      extracellular space, such a transient increase in [K+]e was too small to be
      detected by conventional K+-selective electrodes. Therefore, we developed a
      "shielded ion-sensitive microelectrode" (SIM) that limited diffusion to a small
      compartment, formed by a shielding pipette which surrounded the tip of the K+
      sensitive microelectrode. The SIM improved the signal to noise ratio by a factor
      of at least three, thus transient increases of [K+]e in the vicinity of MDCK-F
      cells became detectable. They occurred at a rate of 1.3 min-1. The cell releases
      40 fmol K+ during each burst of intermittent KCa channel activity, which
      corresponds to about 15% of the total cellular K+ content. Since transmembrane K+
      loss must be accompanied by anion loss and therefore leads to a decrease of cell
      volume, these findings support the hypothesis that intermittent volume changes
      are a prerequisite for the migration of MDCK-F cells.

PMID- 9019734
TI  - Heterooligomeric assembly of inward-rectifier K+ channels from subunits of
      different subfamilies: Kir2.1 (IRK1) and Kir4.1 (BIR10).
AB  - Activities of strong inward-rectifier K+ channels composed of Kir2. 1(84 M),
      Kir2.1(84T) and Kir4.1 subunits and weak inward-rectifier K+ channels composed of
      Kir4.1(E158N) subunits were measured from giant inside-out patches of Xenopus
      laevis oocytes. The conductance/voltage (g/V) relationship for block by
      intracellular spermine (SPM) was biphasic for both Kir2.1 channel types while it
      was monophasic for both Kir4.1 channel types. The release of blocking Mg2+ ions
      was slow for Kir2.1(84T) but virtually instantaneous for Kir2.1(84M) and both
      Kir4.1 channel types. Coexpression of Kir2.1(84T) and Kir4.1(E158N) resulted in
      heterooligomeric channels which were strongly rectifying, with a g/V relationship
      for SPM-evoked block that was significantly different from that of either
      parental homooligomeric channel type. Block by intracellular Mg2+ was markedly
      stronger than that for Kir4.1(E158N) channels, while release of the block was
      almost instantaneous, similar to that for Kir4.1(E158N) channels. This suggests
      preferential formation of a particular heterooligomer such as was recently
      proposed for subunits within the Kir3.0 family.

PMID- 9019735
TI  - Identification of ClC-2-like chloride currents in pig pancreatic acinar cells.
AB  - We used the whole-cell patch-clamp technique to identify a hyperpolarization
      activated Cl- current (approximately 50 pA/pF at -60 mV) in acutely isolated,
      voltage-clamped, single, pig pancreatic acinar cells. This current had
      characteristic properties of inward rectification, a Cl- = Br->I- selectivity
      sequence and activation by extracellular hypotonicity. These properties are
      similar to those reported for the ClC-2 Cl- channel recently cloned from rat and
      expressed in oocytes. An antiserum raised against the C-terminus of ClC-2
      localized the channel to secretory granules containing amylase that were situated
      exclusively at the apical pole of the pig pancreatic acinar cells, but the
      channel was not localized in the basolateral membrane. Our study combines a
      functional assessment and immunohistochemical localization of ClC-2-like channels
      in a native mammalian cell. The data suggest that the ClC-2-like Cl- channel may
      function as a Cl- efflux pathway in pancreatic acinar cells.

PMID- 9019736
TI  - Uptake of human urinary trypsin inhibitor by the kidney epithelial cell line, LLC
      PK1.
AB  - We investigated the uptake of human urinary trypsin inhibitor (UTI) by the kidney
      epithelial cells, LLC-PK1. Indirect immunogold techniques with an electron
      microscope demonstrated the localization of UTI within the cells after an
      incubation during which UTI was added to the apical side. Immunoreactivities were
      found in endocytic vesicles, vacuoles and lysosomes. Subsequently, we tried to
      characterize the property of the uptake of UTI using the fluorescein
      isothiocyanate-labelled UTI (FITC-UTI). FITC-UTI uptake was decreased by an
      incubation with an excess of unlabelled UTI and showed concentration-dependent
      saturation. This process was markedly suppressed during the incubation at 4
      degrees C. The uptake was significantly lessened with 2,4-dinitrophenol and
      antimycin A, inhibitors of oxidative phosphorylation, and colchicine, a
      microtubule-depolymerizing agent. These results indicate that exogenous UTI is
      internalized by LLC-PK1 cells through an endocytic pathway. From uptake studies,
      it is suggested that an adsorptive process is partially involved in the
      mechanisms of endocytosis.

PMID- 9019737
TI  - Measurement of the movement of the S4 segment during the activation of a voltage
      gated potassium channel.
AB  - Voltage-gated ion channels contain a positively charged transmembrane segment
      termed S4. Recent evidence suggests that depolarisation of the membrane potential
      causes this segment to undergo conformational changes that, in turn, lead to the
      opening of the channel pore. In order to define these conformational changes in
      structural terms, we have introduced single cysteine substitutions into the S4
      segment of the prototypical Shaker K+ channel at various positions and expressed
      the mutants in Xenopus oocytes. The cells were depolarised to induce K+ currents
      and the effect of application of 100 microM parachloromercuribenzenesulphonate
      (PCMBS) on these currents was examined by the two-electrode voltage-clamp
      technique. PCMBS inhibited K+ currents elicited by mutants L358C, L361C, V363C
      and L366C, but not those by V367C and S376C. Since PCMBS is a membrane
      impermeable cysteine-modifying reagent, the data suggest that depolarisation must
      have caused the S4 segment to move out of the lipid bilayer into the
      extracellular phase rendering the residues at positions 358, 361, 363 and 366
      susceptible to PCMBS attack. The lack of effect of PCMBS on V367C suggests that
      the exposure of S4 terminates at L366. Detailed analysis of L361C mutant revealed
      that the S4 movement can occur even below the resting potential of the cell, at
      which potential voltage-gated K+ channels are normally in a non-conducting closed
      state.

PMID- 9019739
TI  - Article on radiation therapy contained inaccuracies.

PMID- 9019738
TI  - The effect of intracellular pH on cytosolic Ca2+ in HT29 cells.
AB  - The influence of intracellular pH (pHi) on intracellular Ca2+ activity ([Ca2+]i)
      in HT29 cells was examined microspectrofluorometrically. pHi was changed by
      replacing phosphate buffer by the diffusible buffers CO2/HCO3- or NH3/NH4+ (pH
      7.4). CO2/HCO3- buffers at 2,5 or 10% acidified pHi by 0.1, 0.32 and 0.38 pH
      units, respectively, and increased [Ca2+]i by 8-15 nmol/l. This effect was
      independent of the extracellular Ca2+ activity and the filling state of
      thapsigargin-sensitive Ca2+ stores. Removing the CO2/HCO3- buffer alkalinized pHi
      by 0.14 (2%), 0.27 (5%), and 0.38 (10%) units and enhanced [Ca2+]i to a peak
      value of 20, 65, and 143 nmol/l, respectively. Experiments carried out with Ca2+
      free solution and with thapsigargin showed that the [Ca2+]i transient was due to
      release from intracellular pools and stimulated Ca2+ entry. NH3/NH4+ (20 mmol/l)
      induced a transient intracellular alkalinization by 0.6 pHunits and increased
      [Ca2+]i to a peak (Delta [Ca2+]i = 164 nmol/l). The peak [Ca2+]i increase was not
      influenced by removal of external Ca2+, but the decline to basal [Ca2+]i was
      faster. Neither the phospholipase C inhibitor U73122 nor the inositol 1,4,5
      trisphosphate (InsP3) antagonist theophylline had any influence on the NH3/NH4+
      stimulated [Ca2+]i increase, whereas carbachol-induced [Ca2+]i transients were
      reduced by more than 80% and 30%, respectively. InsP3 measurements showed no
      change of InsP3 during exposure to NH3/NH4+, whereas carbachol enhanced the InsP3
      concentration, and this effect was abolished by U73122. The pHi influence on
      "capacitative" Ca2+ influx was also examined. An acid pHi attenuated, and an
      alkaline pHi enhanced, carbachol- and thapsigargin-induced [Ca2+]i influx. We
      conclude that: (1) an alkaline pHi releases Ca2+ from InsP3-dependent
      intracellular stores; (2) the store release is InsP3 independent and occurs via
      an as yet unknown mechanism; (3) the store release stimulates capacitative Ca2+
      influx; (4) the capacitative Ca2+ influx activated by InsP3 agonists is decreased
      by acidic and enhanced by alkaline pHi. The effects of pHi on [Ca2+]i should be
      of relevance under many physiological conditions.

PMID- 9019740
TI  - Cancer resources in the United States.

PMID- 9019741
TI  - [Cytotoxin vacuolization of Helicobacter pylori].
AB  - Helicobacter pylori is now recognized as the major causative agent of chronic
      superficial gastritis in humans. The virulence factors of H. pylori are still
      poorly understood. Vacuolating cytotoxin (VacA) is one of the factors that has
      been identified so far. VacA induces cytoplasmic vacuolation in eukaryotic cells.
      The vacA gene encodes a precursor protein of 140 kDa which consists of a 33-amino
      acid signal sequence, the 87 kDa cytotoxin and a 50 kDa C-terminal domain. The 50
      kDa domain is involved in translocation of VacA across outer membrane. Sequence
      analysis of vacA gene derived from different strains of H. pylori revealed the
      existence of several families of vacA gene allels. Analysis of a clinically
      isolated strains of H. pylori showed the correlation between presence of specific
      vacA allels, VacA activity and peptic ulceration.

PMID- 9019742
TI  - [The role of genetically determined oxidation of drugs and xenobiotics in
      pathogenesis of neoplastic diseases].
AB  - The relationship between genetically determined polymorphic hepatic oxidation and
      susceptibility to neoplastic diseases have aroused much interest. Some studies
      provide evidence of a possible association between oxidation phenotype,
      especially extensive and very extensive phenotype, and increased risk of the
      development of cancers. This work presents modern views on that subject.

PMID- 9019743
TI  - [Neutrophil activation by bacterial endotoxins].
AB  - The endotoxin (lipopolysaccharide, LPS), major component of Gram-negative
      bacteria cell wall, activate numerous types of cells, neutrophils included. The
      chemical compositions of polysaccharide (O-specific polysaccharide and core
      oligosaccharide) and hydrophobic lipid A parts of LPS are presented. The bindings
      of LPSs to neutrophils resulted in signal transduction and neutrophils
      activation. Neutrophils, under LPS stimulation, generate oxygen radicals, nitric
      oxide and other components of inflammatory processes.

PMID- 9019744
TI  - [Subunits gamma and zeta of Fc receptors. Structure and function].
AB  - This article describes briefly the recent data on the genes and structure of Fc
      receptors. Structure and function of subunits gamma and zeta of Fc receptors are
      presented. A special emphasis is given to their role in signal transduction.

PMID- 9019745
TI  - [Cytolysins and homologous proteins produced by gram-negative bacteria. II.
      Hemolysins of Aeromonas, Serratia, Proteus and Morganella and proteins from gram
      negative bacteria related to cytolysins].
AB  - This article presents the genetic determination, synthesis and activation of
      hemolysins produced by mentioned above bacteria, as well as the possible role of
      these toxins in the pathogenicity. All these cytolysins are related to RTX
      proteins presented to the previous paper. The short information about cytotoxic
      proteins from other Gram-negative bacteria (P. aeruginosa, K. pneumoniae,
      Vibrionaceae, G. vaginalis) and homologous proteins from E. chrysanthemi and R.
      leguminosarum biovar viciae are also included.

PMID- 9019746
TI  - [Function of metallothionein in the body].
AB  - Metallothioneins are intracellular proteins binding metals. There proteins are
      involved in zinc and copper homeostasis as well as in organism detoxication of
      heavy metals. The induction of metallothioneins synthesis is caused not only by
      metal ions but also by the interleukins, by tumor necrosis factor and by
      glycocorticoids or the stressing factors. Metallothioneins prove the protective
      action in cadmium toxication and prevent interaction of cadmium with thiol groups
      -SH proteins. In neoplasms the increase of metallothionein level occurs both in
      tumors and in liver, the level of these proteins is correlated with the size of
      the tumor.

PMID- 9019747
TI  - [Molecular effects of chromium compound activity].
AB  - Chromium(VI) compounds produce a variety of DNA damage such as DNA single strand
      breaks, alkali-labile sites and DNA-protein cross-links in vivo and in cultured
      cells. Chromium(III) compounds bound to isolated DNA and proteins. Cr(VI) readily
      entered cell through general anion channels. In contrast, Cr(III) did not readily
      cross cell membranes. Inside cells Cr(VI) is reduced through intermediates to
      Cr(III) by cellular reductants. Reactive intermediates formed during
      intracellular Cr(VI) reduction might be responsible for some chromate
      genotoxicity. Ascorbic acid decreases chromate induced alkali-labile sites and
      chromium inhibition of glutathione reductase, but it enhances DNA-protein cross
      links and cytotoxicity caused by this metal.

PMID- 9019748
TI  - [Invasive pneumonia diagnosis in community-acquired pneumonia].

PMID- 9019749
TI  - [Experiences with fluorescence diagnosis and photodynamic therapy in a
      multimodality therapy concept of operated, recurrent bronchial carcinoma].
AB  - Even of those few patients who are operated because of bronchial cancer up to a
      quarter develop a recurrence. One reason is certainly that tumor-cells already
      present at the time of surgery are bronchoscopically invisible. Fluorescence
      methods might be able to detect these malignant cells. For patients with post
      surgical recurrences the therapeutical choices are limited due to the loss of
      parenchyma. Photodynamic therapy (PDT) with the hematoporphyrine derivative
      Photofrin is one laborious but promising option. Based on an argon-dye laser we
      have developed a combined system for the diagnostical measurement of
      autofluorescence and Photofrin-induced fluorescence at 488 nm and the
      therapeutical PDT at 630 nm. Under the excitation with blue light from the argon
      laser, differences in the autofluorescence of malignant and benign cells can be
      distinguished. Following the injection of Photofrin a spectrum peak at 628 nm
      clearly delineates tumor cells. In six out of twelve patients with post-surgical
      recurrences a single PDT course resulted in tumor eradication. With additional
      PDT courses and brachytherapies local tumor control could be achieved in all
      cases. The general photosensitivity and the necessary light protection were
      tolerated by all patients. In order to avoid severer complications such as
      asphyxia, obstruction of bronchi and pneumotharaces resulting from fibrin-plugs
      and necrotic tissue following PDT must be considered. Especially in patients with
      pneumonectomy a careful surveillance and debridement is mandatory.

PMID- 9019750
TI  - [Dangerous complication of transtracheal oxygen therapy with the SCOOP(R)
      system].
AB  - A portable oxygen system in combination with transtracheal O2 delivery (SCOOP(R))
      permits patients with respiratory failure optimal mobility and facilitates
      longterm oxygen therapy. This report describes a 70 year old female with COPD
      that developed acute respiratory distress 18 days after inserting PRESCOOP(R) and
      11 days after changing to SCOOP 1 catheter. Catheter stripping had not revealed
      any pathology. Flexible bronchoscopy showed a mucus ball at the catheter tip
      leading to a 80% stenosis of the trachea. Trials to remove the ball with forceps
      and a loop were not successful until a rigid bronchoscop was inserted. Up to 10%
      of patients develop mucus ball formation with SCOOP 1 catheter which remains in
      situ for 6 weeks. In patients with high risk of mucus formation (high O2 flow,
      viscous mucus, low FEV1) the manufacturers of SCOOP recommend catheter stripping.
      We consider a control bronchoscopy being safer 1 week after changing from
      PRESCOOP to SCOOP because one patient has been reported to have died of this
      complication and our patient has developed a near fatal situation.

PMID- 9019751
TI  - [MRSA (methicillin-resistant Staphylococcus aureus) infections in patients with
      pulmonary diseases].
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial
      pathogen. We investigated MRSA-infections in patients with pulmonary diseases
      referring to epidemiological aspects. Between 9/92 and 2/92 we found MRSA
      infections in our hospital in 24 patients (11 female, 13 male, average age 54.6
      years). Clinical presentation, main and accompanying disorders and previous
      antibiotic therapy regimens were registered. Strains were typed using DNA-RFLP
      and lysotyping. MRSA detection were done in specimen from sputum (12/24) and from
      the bronchial secret (9/24). In 18/24 cases the MRSA-colonisation was associated
      with infection. In 15/24 cases the first acquisition of MRSA happened in our
      hospital, 6/24 times the germ was carried off other institutions and in 3/24
      cases it was possibly community acquired. Most frequently patients suffered from
      bronchial cancer (6/24), from chronical bronchitis (5/24), from pneumonia (4/24)
      or Cystic fibrosis (4/24). Usually the patients showed other severe comorbidity.
      13/24 patients had an antibiotic course before detecting MRSA. Typing revealed a
      strain already known in different hospitals of Berlin, another known strain of
      northern Germany and two so far unknown strains. Of interest was a different
      behaviour of resistance and the lost of resistance of strains in the course. MRSA
      infection in pulmonary medicine emerged as a problem mostly in patients with
      multimorbidity and severe underlying diseases. Change of resistance in strains
      and new strains were observed.

PMID- 9019752
TI  - [Community-acquired pneumonia requiring inpatient treatment: outcome and
      prognostic rule].
AB  - OBJECTIVE: Mortality in community-acquired pneumonia (CAP) may be reduced by
      early identification of patients requiring intensive care treatment. The purpose
      of the study was to determine prognostic factors of outcome in patients with CAP
      in order to establish a clinically applicable discriminant rule. METHODS: 93
      episodes of 92 patients with CAP were reviewed with regard to epidemiological,
      clinical, laboratory and microbiologic data. The prognostic analysis included a
      univariate as well as a multivariate approach in order to identify parameters
      correlated with death using the Cox regression hazard function in a backward
      stepwise selection model. The three parameters found to contribute most to the
      significance of the model were used in a discriminant rule for classification of
      outcome. RESULTS: The parameters found to be significantly different between
      survivors and non-survivors were heart rate, systolic, diastolic as well as mean
      blood pressures, leucocyte count, percentage of laymphocytes, and LDH values. The
      multivariate analysis revealed that heart rate, systolic arterial pressure, and
      LDH serum levels were associated best with lethal outcome (overall significance
      of the model p < 0.005). A prognostic rule composed of the variables heart rate >
      or = 90 beats/min, systolic arterial blood pressure < or = 80 mmHg and LDH > or =
      260 U/l achieved a sensitivity of 77%, a specificity of 75% and positive and
      negative predictive values of 42% and 93%, respectively. It was associated with a
      6-fold increased risk of lethal outcome. CONCLUSIONS: Heart rate, systolic blood
      pressure, and LDH values were associated best with death in a multivariate
      analysis. A discriminant rule consisting of these three variables achieved
      favourable classification results. The rule qualifies for further prospective
      validation and may prove useful in the management of hospital treated CAP.

PMID- 9019753
TI  - [Diagnosis of pneumonia in artificial ventilation: principles, techniques,
      results, preliminary recommendations].

PMID- 9019754
TI  - [Current status of interdisciplinary therapy of stage III non-small-cell
      bronchial carcinoma].

PMID- 9019755
TI  - [Comments on the contribution "New developments in non-tuberculous
      mycobacterioses"].

PMID- 9019756
TI  - [Cellular and subcellular morphology of the repair process in pulmonary
      tuberculosis].
AB  - The repair processes in pulmonary tissue and granuloma in experimental
      tuberculosis were studied electron-microscopically and histochemically. At the
      beginning of inflammation they manifest at the ultrastructural level in
      aerohematic barrier cells. The period of granuloma formation is characterized by
      cell hypertrophy, particularly of type II alveolocytes, intensive macrophagal
      reaction, and increased functional activity of more and more cells.
      Ultrastructural and functional differences in epithelioid and multinuclear giant
      cells are revealed. A progressive course of tuberculosis involves decompensation
      of the compensatory and repair processes. Contrary to this, during chemotherapy
      of tuberculosis repair reactions predominate, resolution of inflammatory changes
      is in progress, cell populations in the granuloma change, and it is separated
      from the adjacent pulmonary tissue.

PMID- 9019757
TI  - [Progress and prospects of tuberculosis immunology and immunogenetics].
AB  - Reviews the recent progress in immunopathogenesis, immunogenetics,
      immunodiagnosis, immunotherapy, and immunoprophylaxis of tuberculosis. The
      findings of Russian scientists (primarily at the Central Research Institute of
      Tuberculosis, Russian Academy of Medical Sciences) are compatible to the results
      of medical centers abroad.

PMID- 9019759
TI  - [The Central Research Institute of Tuberculosis of the Russian Academy of Medical
      Sciences is 75 years old].

PMID- 9019758
TI  - [Molecular mechanisms of cell-to-cell interactions during the progress and
      healing of tuberculosis].
AB  - The role of some protein systems of humoral regulation and of some lipid
      mediators in the development, course, and outcomes of tuberculous inflammation
      has been studied. The authors discuss regularities in the changes of the
      kallikrein-kinin system, blood clotting and fibrinolysis systems, proteinase
      inhibitor balance, pool and functional activity of fibronectin in the blood and
      various parts of the respiratory systems, shifts in the content and ratios of
      prostaglandins E and F2 alpha in pulmonary tissue and bronchoalveolar space, in
      the level of platelet activation factor in liquid biological media and various
      types of phagocytizing cells. Shifts in all these systems are uniform, starting
      from acute-phase mobilization and eventuating in loss of autoregulation and
      depletion. Changes in all the above-listed systems of humoral regulation are due
      to the bactericidal activity of phagocytes, specific features of the cytogram of
      bronchoalveolar lavage, vascular permeability, morphological characteristics, and
      course and outcomes of the tuberculous process in the lungs.

PMID- 9019761
TI  - [Efficacy of clinical follow-up of patients with tuberculosis of the respiratory
      organs in terms of their cure under present-day epidemiological conditions].
AB  - A total of 884 newly detected patients with tuberculosis of the respiratory
      organs with degradation were followed up for 9 years (1987-1995). Control group
      consisted of 1419 patients with respiratory tuberculosis without degradation. As
      a result of treatment, the destruction focus was healed in 3 years in 73.4%
      patients and bacteria no longer released in 77.4%. Remote results (after 3, 6,
      and 9 years) indicate that adequate treatment helps attain cure during the second
      and third year of the follow-up. Untimely transfer of the patients into inactive
      groups (40.4% after 3 years) leads to early relapses of tuberculosis, and thus
      groups of chronic patients are formed both among tuberculosis patients with
      initially detected destruction and without it (4.5 and 2.2%, respectively). The
      number of clinically cured patients by the end of the ninth year was 56.6 and
      77%, respectively; 7.4 and 4.7% patients were still registered in the active
      groups.

PMID- 9019760
TI  - [New microbiological Techniques in diagnosis of tuberculosis].
AB  - Microbial spectrum in patients with disorders of the upper respiratory tract
      consisted mainly of streptococci, staphylococci and pneumococci in 1991-1993,
      1994 and later, respectively. Most specific for detection of nontuberculous flora
      was brushing with protecting agar plugs in combination with transport medium and
      anaerobic culturing. Direct immunofluorescence allows detection of antigens M.
      chlamydia in 29.4%, M. pneumoniae in 18.5% of cases. In diagnosis of tuberculosis
      the following new technologies were introduced: bacterioscopy with previous
      culturing of the material on liquid culture media followed by biological test and
      polymerase-chain reaction; determination of drug resistance based on nitrate
      reductase activity of M. tuberculosis indicating resistance of M. tuberculosis on
      liquid media in 4-7 days, dense egg media in 8-12 days, usage of Popesku medium
      enables correction of tuberculosis chemotherapy one month after the test
      initiation; M. tuberculosis identification using Western blot with monoclonal
      antibodies in some cases for 7 days.

PMID- 9019762
TI  - [Detection of pulmonary tuberculosis in migrants].
AB  - Tuberculosis was detected in 2.2% of migrants from Baku, whereas among those
      applying for medical and social care to the charity organization "Physicians
      without Boundaries" this value is 4 times higher: 8.6%. These results necessitate
      the development of a complex of antituberculosis measures adapted to new marginal
      risk groups-migrants. The principal purpose of these measures should be to make
      specialized medical care as available as possible for this group.

PMID- 9019763
TI  - [Detection of tuberculosis in homeless persons and their sociopsychological
      characteristics].
AB  - Homeless patients with tuberculosis form a special group. Being out of
      therapeutical-and-prophylactic institutions sight and violating elementary
      sanitary regulations, they are, from an epidemic standpoint, the most dangerous
      part of a tuberculosis reservoir. Tuberculosis morbidity rates in the homeless
      are extremely high and tens times as great as those among other populations. The
      existing system for detecting tuberculosis among the homeless is not very
      effective. Much better results are achieved by nongovernmental philanthropic
      institutions where homeless persons apply to for medical and social aids. About
      half the homeless patients with tuberculosis were referred to Tuberculosis
      Hospital 11 of the International Organization "Physicians Without Boundaries".
      The patient's personality is, in general, the most vivid terms, characterized as
      asthenic; with low intelligence and constitution; asocial, aggressive, and being
      a carrier of the motive of acquired helplessness. This group of patients needs
      not only medical efforts, but sociolegal and sociopsychological rehabilitation.
      The activities of Tuberculosis Hospital 11 wherein a room of social aid and
      rehabilitation has been functioning since 1995 may be an example of a
      comprehensive approach to tackling the problem of homeless patients with
      tuberculosis.

PMID- 9019764
TI  - [Modern social problems in phthisiology].

PMID- 9019765
TI  - [Detection of tuberculosis in children of new risk groups and efficacy of
      chemoprophylaxis].
AB  - 109 children at risk of tuberculosis frequently suffering from acute respiratory
      diseases (ARD) and 87 children with rare ARD have undergone a 3-month course of
      isoniazide chemoprophylaxis. In 95.0% of the examinees the above chemoprophylaxis
      lowered ARD morbidity to 1-2 times a year, reduced and stabilized tuberculin
      sensitivity, prevented tuberculosis. Isoniazide treatment of 87 children whose
      parents worked with cattle that might be infected prevented tuberculosis in them,
      diminished tuberculin sensitivity. It is thought valid that chemoprophylaxis
      should be given in sanatoria primarily to children exposed to two and more risk
      factors (epidemiological, age-sex, medicobiological, social).

PMID- 9019766
TI  - [Tuberculosis in children and adolescents as a social problem].
AB  - Under the conditions of society's socioeconomic instability and increased
      migratory processes, ever increasing numbers of children and adolescents are
      being brought up in socially disadapted families. The social status of a family
      largely determines the infection and morbidity rates of tuberculosis and affects
      the diagnosis, course and prognosis of the disease in children and adolescents.
      The infection rates in this group of children are 2-5 times higher than those of
      children in Russia, the risk of primary infection is 10.9%. In children and
      adolescents from the socially disadapted families, there was a torpid and
      undulating course in 50% of cases, 25% being found to have primary resistance to
      antituberculous drugs, which corresponds to that in the source of infection. To
      enhance the efficiency of antituberculous diagnostic and therapeutic measures
      among children and adolescents from socially disadapted population groups, the
      Ministry of Internal Affairs, public educational institutions, and the general
      therapeutical network should jointly make a complex of measures within the
      framework of a goal-oriented sponsored programme.

PMID- 9019767
TI  - [Tuberculosis thanatogenesis and pathoanatomy of caseous pneumonia].
AB  - Tuberculosis thanatogenesis of today has been studied on autopsy and operative
      material. Pathoanatomy and mechanism of development of caseous pneumonia have
      been investigated: types of tissue reactions and role of terminal and respiratory
      bronchioles in the development of caseous pneumonia are shown and early phases of
      pathological changes of the connective tissue and interstitium (acute
      mesenchymopathy) distinguished. Caseous pneumonia has been distinguished for the
      first time. Its reversible phase may be cured by modern treatment strategy,
      whereas in its irreversible form not only conservative, but urgent surgical
      treatment is indicated.

PMID- 9019768
TI  - [Efficacy of chemotherapy of pulmonary tuberculosis drug-resistant
      m.tuberculosis].
AB  - M. tuberculosis examined in 717 patients with pulmonary tuberculosis appeared
      resistant to chemotherapy in 67.2% of cases. Whereas chronic patients developed
      drug resistance (DR) as secondary DR in 90.2% of cases, new cases with DR (50.1%
      of the examinees) seemed to be infected with drug-resistant M. tuberculosis. 2
      stage chemotherapy with 4-5 drugs terminates bacterial discharge within first 3
      months of treatment in the majority of the patients, especially if early
      correction of chemotherapy is used by the results of early determination M.
      tuberculosis drug sensitivity.

PMID- 9019769
TI  - [Endoscopic diagnosis of tuberculosis and other granulomatous diseases of
      respiratory organs: advances and prospects].
AB  - The paper presents data on the use of various bioptic methods in phthisiatry and
      pulmonology. Particular attention is given to granulomatous diseases of the lung
      whose misdiagnosis may be during clinical examinations in 50-70% of cases. Making
      the methods of transbronchial biopsies, including those of the lung and
      bronchoalveolar lavage, better, putting them into practice widely, and developing
      new studies (microbiological, electron microscopic, immunological, morphological)
      for biopsy specimens may improve the diagnosis of lung diseases.

PMID- 9019770
TI  - [Rationale for the use of regional lymphotropic therapy in the management of
      tuberculosis in adolescents].
AB  - Regional lymphotropic therapy involves the administration of a antituberculous
      drug (isoniazid or canamycin) into the pretracheal cellular space or subaxillary
      region on the damage ipsilateral side with daily alternations of injection sites.
      A hundred and thirty two patients with active tuberculosis types (mainly
      infiltrative) who form two equal groups: main (lymphotropic therapy) and control
      (routine treatments) were followed up. Lymphotropic therapy is well tolerated by
      patients, particularly in the presence of concurrent gastrointestinal diseases,
      produces no adverse reactions, promotes more rapid resolution of infiltrative
      changes and elimination of intoxication signs. A more rapid positive dynamics in
      the main group than that in the control one allows the duration of hospital stay
      to be reduced by 2-2.5 months.

PMID- 9019771
TI  - [Lung microangiopathy in diabetics with lung tuberculosis].
AB  - Histological and electron-microscopic studies of intact lung specimens were
      carried out in 30 patients with pulmonary tuberculosis developing in the presence
      of type I (insulin-dependent) diabetes mellitus. Material for investigation was
      obtained by intrapulmonary biopsy carried out during diagnostic bronchoscopy.
      Signs of adenopathy were detected in lung areas distant from tuberculous in foci
      all the cases. The diabetic origin of this condition was confirmed by expressed
      correlation with changes in the retinal and renal vessels and absence of
      correlation with the duration of tuberculous process. The degree of pulmonary
      adenopathy has a negative impact on the course of tuberculosis and efficacy of
      its therapy.

PMID- 9019772
TI  - [Dynamics of isolation of mycobacterium tuberculosis during 2-stage standard
      chemotherapy].
AB  - Two-stage standard chemotherapy was performed in 149 newly detected patients with
      pulmonary tuberculosis, by isolating Mycobacteria. Within the first 2 months, the
      patients received 4 drugs: isoniazid, rifampicin, pyrazinamide, streptomycin or
      ethambutol. Treatment with two agents (isoniazid and rifampicin) was continued
      for 4 months. Mycobacterial isolation was stopped in 104 patients after 2 months
      of treatment, in other 26 after 3 months, which amounts to 80.2%. Higher
      therapeutical results were observed in patients who had isolated Mycobacteria
      resistant to 1 and even 2 drugs.

PMID- 9019773
TI  - [Lasers in combined modality treatment of patients with pulmonary tuberculosis].
AB  - Low-energy lasers were used in the combined preoperative treatment and therapy of
      548 patients with chronic fibrocavernous tuberculosis. Indications for some types
      of exposure were defined, namely, transcutaneous exposure of the tuberculous
      involvement zone, combination of transcutaneous laser exposure and laser
      puncture, intravenous and endocavitary laser exposure. Low-energy lasers, as a
      many-factor pathogenetic exposure, are conducive to a more rapid and effective
      stabilization of tuberculosis progress, which helps sooner prepare the patients
      to surgical interventions and in some patients even do without them, reduce the
      number of postoperative complications, and improve the efficacy of surgical
      treatment of grave patients.

PMID- 9019774
TI  - [Correction of bronchial obstructive syndrome and antituberculous drugs-induced
      eosinophilia in patients with pulmonary tuberculosis by using plasmapheresis].
AB  - The paper provides the results of a follow-up of 70 patients with active
      pulmonary tuberculosis in whom the administration of antituberculous drugs
      induced eosinophilia and bronchial obstructive syndrome. To eliminate the side
      effects of antituberculous therapy, a plasmapheresis regimen was performed in 44
      patients, the remaining patients were given only bronchodilators and
      antihistamine drugs. Plasmapheresis as a means for correcting drug-induced
      eosinophilia and bronchial obstructive syndrome was found to be more effective
      than drug therapy and, in some cases, enabled antituberculous therapy to be
      continued, without changing a combination of drugs. It is recommended that
      plasmapheresis should be used in cases of inadequate efficiency of conventional
      methods for correcting drug intolerance.

PMID- 9019775
TI  - [Increased apoptosis of immunocompetent cells as a possible mechanism in the
      development of immunodeficiency in patients with acutely progressive
      tuberculosis].
AB  - The formation of immunodeficiency whose likely mechanism is apoptosis of some
      immunocompetent cells was studied in 35 patients with caseous pneumonia. The
      leading clinical sign of apoptosis in acutely progressive tuberculosis is
      significant lymphopenia (4-10%). Immunological studies indicated a substantial
      reduction in the count of T lymphocytes and their regulatory subpopulations of
      different phenotypes. In vitro mitogenic induction causes a decline of activated
      CD3+, CD4+, and CD8+ cells on the average by 10-40%, a decrease in the
      proliferative and synthetic functions, as compared with those in patients with
      infiltrative tuberculosis of the lung and healthy donors. Cytochemical findings
      in the same patients show that half the lymphocytes in the blood samples from
      patients with caseous pneumonia has profound intracellular metabolic
      disturbances. These cells are unavailable and undergo apoptosis, which determines
      immunodeficiency in patients with acutely progressive tuberculosis.

PMID- 9019776
TI  - [Chemotherapy-induced lung functional changes in patients with destructive
      pulmonary tuberculosis].
AB  - Lung function has been found to be altered in the overwhelming majority of
      patients with destructive pulmonary tuberculosis treated with drugs, only
      positive or only negative functional changes being relatively rarely observing.
      Combined positive and negative functional changes are much frequently revealed.
      The direction and magnitude of the revealed functional changes depend on the
      efficiency of tuberculosis treatment and on the specific features of a healing
      process. A thorough assessment of pulmonary functional changes can be made only
      on the basis of comprehensive studies of lung volumes, elasticity, and bronchial
      patency, by recording these parameters.

PMID- 9019777
TI  - [Sarcoidosis: 25-year clinical follow-up].
AB  - Based on the follow-up of 1,600 patients with sarcoidosis from 1971 to 1996, the
      authors analyzed the value of various methods for identifying the disease, the
      frequency and nature of misdiagnoses. They showed the efficiency of basic
      treatments in patients with sarcoidosis: corticosteroidal hormones, nonhormonal
      antiinflammatory drugs, plasmapheresis, and physiotherapy. Recurrencies and
      progression were seen in 23.85% of patients. The likely causes of recurrent
      sarcoidosis are considered. It is concluded that recurrencies are one of the
      important problems of modern sarcoidosis.

PMID- 9019778
TI  - [Scintigraphic evaluation of 67GA citrate in the comprehensive study of diffuse
      pulmonary lesions].
AB  - Scintigraphic evaluation of 67Ga citrate was made in 102 patients with diffuse
      pulmonary lesions (DPL) of various genesis. There was respiratory sarcoidosis in
      40 patients, exogenous allergic alveolitis in 47, idiopathic fibrosing alveolitis
      in 3, histiocytosis X in 6, and carcinomatosis in 6. Radionuclide findings
      indicated that the radioagent accumulated in intrathoracic lymph nodes of the
      mediastinum and partially in the lung tissue in 75.5% of cases at the acute stage
      of the disease, negative results were in 24.5%, as explained by the fact that the
      studies were conducted at remission or in the presence of pneumosclerosis.
      Reexaminations of DPL patients using 67Ga citrate may yield objective information
      on the treatment performed and, if the latter fails, correct it.

PMID- 9019779
TI  - [Occupation exogenous allergic alveolitis].
AB  - In 510 patients with exogenous allergic alveolitis (EAA), including poulterers (n
      = 110), tobacco growers (n = 116), wood workers (n = 132), cotton workers (n =
      102), methods for detecting the diseases, its clinical features, course, and
      treatment were studied. The paper gives a scheme of alveolitis development. The
      most effective detection methods were questionnaires and tests for specific serum
      antibodies. EAA runs more severely in poulterers and tobacco growers. Its
      management includes no contact with the allergen, as well as drugs and
      extracorporeal treatment. Fungal infection exerts a substantial effect on the
      course of the disease.

PMID- 9019780
TI  - [Advances in microbiological diagnosis of tuberculosis and sarcoidosis].
AB  - Combined microbiological investigation of diagnostic material containing granular
      mycobacteria has revealed cultures-revertants both in tuberculous and sarcoidosis
      patients. Identification of the isolated cultures provided the conclusion on
      identity of granular mycobacterial structures discovered both in tuberculous and
      sarcoidosis patients.

PMID- 9019781
TI  - Recombinant human migration inhibitory factor has adjuvant activity.

PMID- 9019782
TI  - Proceedings of 2nd International Workshop on Cell Membrane Pathology in
      Schizophrenia. London, United Kingdom, 6-8 October 1995. Special issue dedicated
      to the memory of Dr. Sukdeb Mukherjee.

PMID- 9019783
TI  - Hypothalamic integration of circadian rhythms. Proceedings of the 19th
      International Summer School of Brain Research. Amsterdam, The Netherlands, 28-31
      August 1995.

PMID- 9019784
TI  - [Prevention of nausea and vomiting in the postoperative period].

PMID- 9019785
TI  - [High-frequency jet ventilation with the HFV 970 prototype in laryngeal
      microsurgery: comparison of 2 injection systems].
AB  - OBJECTIVE: To describe the results obtained with the use of a high frequency jet
      ventilation system with the HFV 970 prototype through two types of injector, an
      intratracheal cannula and an endotracheal tube, in 12 patients undergoing
      laryngoscopic microsurgery. PATIENTS AND METHOD: After anesthetic induction with
      propofol and succinylcholine, an intratracheal cannula was placed in the patients
      in group A by way of cricothyroid membrane puncture. The tracheas of group B
      patients were intubated with a number 7 tube, through which was inserted the same
      type of cannula as had been used with group A patients. A prototype Servo HFV 970
      respirator was used with the following protocol: minute volume 120 ml/min,
      inspiratory time 30%, respiratory rate 120 cycles/min and a FiO2 of 1. Anesthesia
      was maintained with propofol in continuous perfusion. The parameters studied were
      peak airway pressure, PCO2, PO2 and pH. Data were recorded at baseline and every
      5 min thereafter until the end of surgery. RESULTS: During high frequency jet
      ventilation there were no statistically significant differences between groups A
      and B with respect to peak airway pressure. PCO2 in group A increased
      significantly during surgery, while in group B it decreased significantly.
      Oxygenation was excellent in both groups, being significantly higher than
      baseline values at all times studied, with no statistically significant
      differences between the 2 groups. CONCLUSION: Our results for the efficacy of
      ventilation and oxygenation with the prototype HFV 970 are similar to those
      published for conventional high frequency jet ventilation. Using a tracheal tube
      assures adequate ventilation, but supposes a tendency to entrapment, whereas use
      of an intratracheal cannula is associated with lower ventilatory efficacy and
      less entrapment. Oxygenation is excellent with both systems.

PMID- 9019786
TI  - [Succinylcholine induces hyperpotassemia in patients in critically ill patients].
AB  - OBJECTIVE: To study changes in kalemia caused by succinylcholine administration
      to patients in critical care, and the possible association of succinylcholine
      with clinical and analytical data, severity-of-disease classification, duration
      of stay in the intensive care unit (ICU) and immobility. PATIENTS AND METHODS:
      Twenty-three patients admitted to the ICU, none of whom suffered burns,
      polytrauma or neuromuscular disease, and who had received 1.5 mg/kg
      succinylcholine on 28 occasions, usually to facilitate tracheal intubation.
      Kalemia was analyzed before neuromuscular relaxation and 5 and 30 min afterwards.
      Electrocardiographic II and V5 derivations and invasive arterial pressure were
      monitored in all patients. The increase in kalemia at 5 min correlated with age,
      sex, weight, APACHE II score, days in ICU, current and accumulated immobility,
      and analytical parameters such as glycemia, creatinine, GOT, bilirubinemia, pH
      and creatine kinase. The kalemia of these patients was compared with that of 15
      patients in acceptable general state who had undergone scheduled surgery.
      RESULTS: Kalemia increased significantly from a mean baseline level of 4.2 (0.9)
      mEq/l to 5.5 (1.4) at 5 min and 4.6 (0.9) at 30 min in ICU patients. In the non
      ICU patients there were no statistically significant changes. Kalemia at 5 min
      was correlated with baseline (r = 0.84; p < 0.0001), days in the ICU (r = 0.39; p
      < 0.05) and weight (r = 0.46; p < 0.05). The mean increase in kalemia at 5 min
      was 0.5 mEq/l in patients who stayed less than 10 days, 1.8 mEq/l in those whose
      stay was from 10 to 30 days and 1.4 mEq/l in patients who stayed longer than 30
      days. The percent increase in kalemia correlated directly (r = 0.7; p < 0.001)
      with days in the ICU and with accumulated immobility in patients whose ICU stay
      was less than 30 days. For ICU stays longer than 30 days the correlation was
      negative (r = -0.98; p = 0.03). Electrocardiographic changes were recorded in 2
      patients with brief sinus bradycardia having no hemodynamic repercussions.
      CONCLUSIONS: The use of succinylcholine in critically ill patients causes a brief
      but significant increase in kalemia, with slight and rare electrocardiographic
      changes. The effect varies according to the length of time spent in the ICU and
      the degree of immobility, with maximum increases seen when the ICU stay is
      between 10 and 30 days. Patient immobility may play an important
      pathophysiological role. The indications for use of succinylcholine in critically
      ill patients should be very strict, particularly during the period of greatest
      sensitivity.

PMID- 9019787
TI  - [Quality in anesthetic management during hepatic transplant. Hepatic Transplant
      Anesthesia Group].
AB  - INTRODUCTION: To measure the quality of anesthetic management during liver
      transplants (LT) and to assess the effect on improving patient care after
      establishing a quality policy based on self evaluation of quality indicators.
      MATERIAL AND METHODS: Two periods were studied: January 1993 through December
      1994 (93 LT) and March 1995 through November 1995 (45 LT). Compliance with the
      anesthetic protocol was assessed by way of 14 indicators as follows: exposure and
      analysis of the results for the 1993-1994 period followed by later evaluation of
      quality indicators for the period 1995. RESULTS: The index for revascularization
      of the graft was lower than any of the following six indicators: temperature,
      systolic arterial pressure, hemoglobin, fibrinogen, pH value and sodium values
      over 155 mmol/l. In the phase during which the liver was removed, the indicator
      for calcium level lower than 1 mmol/l was the only indicator with low compliance.
      Multiple regression analysis showed that mechanical ventilation was associated to
      transfusion requirements, to non compliance with hemostatic and coagulation
      indicators, and to presence of a decrease in systolic arterial pressure below 70
      mmHg. CONCLUSION: We conclude that adverse effects can be partially improved by
      implementing a quality policy based exclusively on analysis of results and
      ongoing professional training. The impact of non compliance with the indicators,
      policy structure and process of delivering health care should be explored.

PMID- 9019788
TI  - [Maria Oliveras: pioneer of neuroanesthesia in Catalonia].
AB  - Maria Oliveras Collelmir (1910) was the first woman to practice anesthesiology in
      Catalonia and one of the first physicians to receive formal training in the
      specialty at the important Nuffield Department of Anaesthetics in Oxford. She
      pioneered the use of general anesthesia with tracheal intubation for
      neurosurgery. This article relates how Dr. Oliveras introduced general anesthesia
      with endotracheal intubation for neurosurgery in Catalonia and pays well-deserved
      homage to this enterprising woman, who overcame family obstacles and social
      prejudices of the time to become the first female anesthesiologist in Catalonia.

PMID- 9019789
TI  - [Parenteral nutrition].

PMID- 9019790
TI  - [Glomus jugulare tumor: perioperative management].
AB  - Surgical treatment of glomus jugulare tumors yields high rates of perioperative
      morbidity and mortality for several reasons, among them neuroendocrine secretory
      activity, a high degree of vascularization, intracranial extension, duration of
      surgery and cranial nerve lesion. Secretory activity (e.g. catecholamines and
      serotonin) should be investigated before surgery and treated appropriately.
      Carotid arteriography (and ball occlusion) are useful to assess vascularization
      of the tumor and determine the need to clamp the carotid artery during the
      procedure. Potential complications such as hemodynamic alterations (bleeding or
      endocrine response), pulmonary embolism (air or thrombotic), hypothermia, facial
      nerve lesion, should be monitored for during surgery. After surgery cranial nerve
      involvement, which can lead to dysphagia and bronchoaspiration, must be looked
      for; the risk of cerebro-spinal fluid fistula is also high. We report the case of
      a woman who underwent surgery for a non secreting glomus jugulare tumor with
      extradural intracranial invasion. The main complications during surgery were
      bleeding with hemodynamic repercussions, pulmonary embolism, lesions in the VII,
      VIII and X cranial nerves, and opening of the dura mater (which required
      insertion of an intradural drain to prevent formation of a fistula). After
      surgery oral intake was delayed until intestinal function was established and
      glottic sphincter competence was verified by fiberoptic laryngoscopy. The only
      complication presenting at this time was cephalea, which disappeared upon removal
      of the drain on day 4. The patient was released on day 10.

PMID- 9019791
TI  - [Unilateral post-bilobectomy pulmonary edema originating from thrombosis of the
      pulmonary vein].
AB  - Foucart (1875) and Ortner (1899) were the first to describe unilateral pulmonary
      edema as a complication of drainage of hydrothorax. Although various causes have
      been reported for this entity, it continues to be rare. We report a case of right
      unilateral pulmonary edema due to thrombosis of the superior pulmonary vein that
      was detected while a patient was in the recovery room after bilateral lobectomy
      for pulmonary tumors. The possible pathophysiological mechanisms contributing to
      pulmonary edema are discussed.

PMID- 9019792
TI  - [Anesthetic considerations of osteopetrosis. Apropos of a case].

PMID- 9019793
TI  - [Use of the laryngeal mask in a case of foreseen impossible intubation].

PMID- 9019794
TI  - [Anesthetic implications of amyloidosis].

PMID- 9019795
TI  - [Modifying our image depends of our interest in it].

PMID- 9019796
TI  - [The Walton Centre for Pain Relief: multidisciplinary focusing in the treatment
      of chronic pain].

PMID- 9019797
TI  - Cardiopulmonary resuscitation training for UK undergraduate dental students.
AB  - Cardiopulmonary resuscitation (CPR) is a vital skill which must be mastered by
      all health care professionals. The General Dental Council recommends that it is
      taught to all UK dental undergraduates. This study was done to elicit how many
      schools teach aspects of Basic and Advanced Life Support to their students, how
      often and whether they assess their students. All UK schools teach Basic Life
      Support (BLS) at least once, but a lower proportion assess their students
      formally and only three schools teach BLS in each year of the course. Only 64%
      (9/14) of respondents thought their students received enough training to be able
      to cope with the initial stages of an emergency on their own. Thus, although the
      level of BLS training is probably acceptable at present, further improvement of
      CPR training in UK Dental Schools is advisable.

PMID- 9019798
TI  - [Cleansing of surgical instruments].

PMID- 9019799
TI  - [Chemical exposure risk in housekeeping work].

PMID- 9019801
TI  - Multiple authorship.

PMID- 9019800
TI  - Brain, drugs and society.

PMID- 9019802
TI  - Multiple authorship.

PMID- 9019803
TI  - EMF statement.

PMID- 9019804
TI  - Combining expert opinions.

PMID- 9019805
TI  - Growth hormone research and therapy.

PMID- 9019806
TI  - Embryologists dismayed by sanctions against geneticist.

PMID- 9019807
TI  - Pig-human transplants barred for now.

PMID- 9019808
TI  - Photons add up to better microscopy.

PMID- 9019809
TI  - Designing therapies that target tumor blood vessels.

PMID- 9019810
TI  - eIF4G: a multipurpose ribosome adapter?

PMID- 9019811
TI  - Human genome agreements.

PMID- 9019812
TI  - Human genome agreements.

PMID- 9019813
TI  - Biologists mobilize against anti-genetics referendum.

PMID- 9019814
TI  - Senate bills back huge increases.

PMID- 9019815
TI  - $1.6 million fraud award overturned.

PMID- 9019816
TI  - Advances painted in shades of gray at a D.C. conference.

PMID- 9019817
TI  - A "master control" gene for fly eyes shares its power.

PMID- 9019818
TI  - Glaucoma gene provides light at the end of the tunnel.

PMID- 9019819
TI  - Akt signaling: linking membrane events to life and death decisions.

PMID- 9019820
TI  - Alzheimer's disease: genotypes, phenotypes, and treatments.

PMID- 9019821
TI  - Thromboelastography. Special issue dedicated to Professor Dr. Hellmut Hartert.

PMID- 9019822
TI  - [The antioxidant histochrome: its effect on lipid peroxidation and the blood
      rheological properties in patients with unstable stenocardia].
AB  - Lipid peroxidation and blood rheology were assessed in the course of treatment
      with antioxidant histochrome and placebo of 66 unstable angina pectoris (UAP)
      patients. Histochrome has a high antioxidant activity and effectively inhibits
      accumulation of lipoperoxides in plasma and red cells of UAP patients, promotes
      stabilization of blood cell function and structures, reduces red cell and
      platelet aggregation.

PMID- 9019823
TI  - [Central hemodynamic function and the correction of heart rhythm disorders at the
      rehabilitation stage in IHD patients].
AB  - Life expectancy and quality of sanatorium rehabilitation for patients with
      macrofocal myocardial lesions vary in line with severity of cardiac arrhythmia
      and left ventricular dysfunction. 24-h monitoring revealed defects in cardiac
      rhythm and conduction in 44.2% of cases. 42% and 36% of patients had ventricular
      extrasystole and high-grade Lown-Wolf ectopy, respectively. Supraventricular
      extrasystole occurred in 7.7%, combined extrasystole in 40% of cases. As to
      hemodynamics type, hypokinetic, hyperkinetic and eukinetic central hemodynamics
      were recorded in 63.0%, 5.2%, 31.8% of cases, respectively. Combinations of
      antiarrhythmic drugs (kilintin + obsidan, cordaron + disopiramide, cordaron +
      kinilentin, kinilentin + verapamil) were selected with consideration of the
      baseline type of central hemodynamics. Combined chemotherapy was more effective
      against different kinds of arrhythmia.

PMID- 9019824
TI  - [The restrictive syndrome in endomyocardial fibrosis and the effect of enalapril
      based on acute drug test data].
AB  - 6 hours after the second dose (5 mg) of enalapril 9 males and 6 females (mean age
      34.93 +/- 1.03 years) with endomyocardial fibrosis (EMF) underwent ECG and pulsed
      Doppler echocardiography to study enalapril effect on cardiohemodynamics. As
      shown by ventricular diastolic function and systolic flow in the pulmonary artery
      with estimation of mean pressure in the pulmonary artery according to Kitabatake,
      enalapril (renitek) affects positively cardiohemodynamics of EMF patients:
      improvement of ventricular diastolic function occurred in line with a significant
      fall in the pulmonary artery pressure. It is noted that application of Doppler
      echocardiography is essential for detection of restriction syndrome.

PMID- 9019825
TI  - [The diagnostic difficulties in a current course of infectious endocarditis].
AB  - The paper reports 152 cases of infectious endocarditis observed in two Moscow
      hospitals. Accurate diagnosis of the disease is complicated by frequent
      nosocomial endocarditis, endocarditis occurrence in aged patients the diagnosis
      in whom requires differentiation with tumors, lymphogranulomatosis, blood
      diseases, etc. To make the diagnosis easier, transesophageal echocardiography and
      comparison of clinical and echo-CG findings were practiced.

PMID- 9019826
TI  - [Bronchial hyperreactivity to the inhalation of hypo- and hyperosmolar aerosols
      and its correction by halotherapy].
AB  - 18 bronchial asthma (BA) patients (12 with mild and 6 with moderate disease) were
      examined before and after halotherapy (HT) for airways reactivity using
      provocative tests with ultrasonic inhalations of purified water (UIPW) and
      hypertonic salt solution (HSS). Bronchial hyperreactivity (BHR) to UIPW and HSS
      before treatment occurred in 13 and 11 patients (72 and 69%, respectively). HT
      reduced BHR in 2/3 and 1/2 of the patients, respectively. In the rest patients
      BHR was unchanged or increased, being so to UIPW only in patients with atopic
      asthma in attenuating exacerbation. Clinical efficacy of HT and initial BHR to
      UIPW correlated (r = 0.56; p < 0.05). No correlation was found between HT
      efficacy and initial BHR to HSS.

PMID- 9019827
TI  - [Absolute diet therapy and antibiotic tolerance in bronchial asthma patients].
AB  - In 10 patients with bronchial asthma (BA) treated conventionally (control group),
      10 BA patients on absolute diet therapy (group 1) and 10 BA patients in absolute
      diet therapy combined with wheat herb juice (group 2) tolerance to 12 antibiotics
      of different classes and some immunity factors were determined using a complex of
      diagnostic methods. The latter implies: case history, humoral and cell immunity
      defense system tests and special tests (chemical erythrograms and leukocyte
      migration inhibition test in plane capillary tubes with tested drugs). The data
      obtained evidence for increased tolerance of the antibiotics in groups 1 and 2 as
      well as for changes in humoral defense system, especially in immunoglobulin E.
      The drug tolerance may be a therapeutic criterion of absolute diet therapy in
      bronchial asthma patients.

PMID- 9019828
TI  - [Nephropathies in a region contaminated by heavy metal salts and the
      possibilities for therapeutic and prophylactic measures].
AB  - The study of the population in the region contaminated with heavy metal salts has
      revealed high incidence of nephropathies even in preschool children manifesting
      initially in the majority of cases with hematuria. All the patients had the signs
      of urinary dysembryogenesis and marked membranopathological process. Long-term
      exposure to even small doses of heavy metals is supposed to cause nephropathy.
      Urinary disease arose more frequently in those genetically predisposed to renal
      and urinary tract affections. Because urolithiasis is a frequent result of
      dismetabolic nephropathy in endemic regions, it is advisable to perform active
      monitoring of children with environmental nephropathy using membrane-stabilizing
      measures. Optimal for these purpose could be xidifon. Further studies are needed
      to elucidate the problem of rapid elimination of heavy metals with chelating
      agents.

PMID- 9019829
TI  - [An initial trial of using continuous ambulatory peritoneal dialysis for treating
      patients with terminal kidney failure].

PMID- 9019830
TI  - [A comparative evaluation of the efficacy of the clinical use of SKN-4M-, SKT-6A-
      and polifepan-type sorbents in treating patients with chronic kidney failure
      (clinical and experimental studies)].
AB  - Enterosorbents were tried clinically in 90 patients with chronic renal failure
      and in vitro (immersion into gastric juice, enteral and colon content).
      Advantages of granulated carbone sorbents over polyphepan, lignin derivative,
      were evident.

PMID- 9019832
TI  - [The Recormon (recombinant erythropoietin) treatment of a patient with
      pancytopenia of the blood and chronic viral hepatitis C].

PMID- 9019831
TI  - [The effect of Recormon therapy on the quality of life of patients on
      hemodialysis treatment].
AB  - Recormon was given to 34 patients on hemodialysis. The drug's effects on quality
      of life were judged by the results of clinical, laboratory, experimental and
      psychological dynamic investigations. The highest effect occurred on the therapy
      month 6-12. Recormon contributed to relief of asthenic and depressive syndromes,
      to an increase of activity and improvement of well-being, quality of life by
      Karnofsky scale within the first year of treatment. The dynamics of life quality
      changes depended on initial psycho-physical condition of the patients, the age,
      blood pressure, hematocrit. Recormon treatment is associated with the risk of
      euphoria.

PMID- 9019834
TI  - [The systolic form of chronic congestive heart failure and its treatment].

PMID- 9019833
TI  - [Drug intolerance].
AB  - The authors present experimental data on luminol-dependent neutrophil
      chemiluminescence of blood from patients with drug intolerance. A decrease in
      intensity of neutrophil and whole blood chemiluminescence was registered in the
      presence of intolerated drugs. In acute phase of generalized intolerance reaction
      the chemiluminescence test showed readiness of the blood cells to react
      inadequately to the contact with different drugs leading to variations in
      generation of active oxygen forms. Improvement in patients' condition was
      followed by narrowing spectrum of drugs causing a decrease in the intensity of
      the chemiluminescence. Later, the chemiluminescence ratio remained low in testing
      only those drugs causing intolerance reaction.

PMID- 9019835
TI  - [Visceral lesions in alcoholism].
AB  - Rich clinical material has been gained on carbohydrate and lipid metabolisms,
      cardiovascular, hepatic, pancreatic, gastric parameters in chronic alcoholics.
      Functional and morphological changes correlated with duration of chronic
      alcoholism. No definite relationship existed between the stage of alcoholism and
      alterations in laboratory and instrumental findings in the course of abstinence
      syndrome.

PMID- 9019836
TI  - [Trimetazidine (Preductal). A new approach in controlling myocardial ischemia].

PMID- 9019838
TI  - [Chronic obstructive bronchitis (the current views on its diagnosis and
      treatment)].

PMID- 9019839
TI  - [Gastroesophageal reflux disease (its pathogenesis, diagnosis and treatment)].

PMID- 9019837
TI  - [Angiotensin-II receptor blockers].

PMID- 9019840
TI  - [Schonlein-Henoch hemorrhagic vasculitis (II)].

PMID- 9019841
TI  - [The use of acetylsalicylic acid in IHD].

PMID- 9019842
TI  - [A trial of the use of low-molecular-weight heparin (fraksiparin) in myocardial
      infarct].
AB  - Efficacy and safety were studied of nonfractionated versus low-molecular
      heparines (NFH, LMH) in acute myocardial infarction (AMI). A total of 99 AMI
      patients entered the trial including those after thrombolytic therapy. The
      highest preventive effect in respect to both venous and arterial thrombosis was
      achieved at subcutaneous administration of NFH in twice daily dose 12500 U and
      LMH in a single daily dose 25000 U. High doses of LFH promoted hemorrhagic
      complications which were absent in administration of LMH. NFH had a proaggregant
      action on the platelets. It is concluded that LMH is an effective and safe
      modality in the treatment of AMI patients acting through inhibition of activity
      of blood coagulation factor X, antiaggregant effect on platelets, improving
      microrheology of red cells and activation of fibrinolysis.

PMID- 9019844
TI  - [Chronic obstructive lung diseases (the current concepts and prospective
      trends)].

PMID- 9019845
TI  - [Sexual abuse of children].

PMID- 9019843
TI  - [The modern view of the history of Beethoven's disease].

PMID- 9019846
TI  - [May the epidemic of diabetes be stopped?].

PMID- 9019847
TI  - [Diabetes mellitus in pregnancy].

PMID- 9019848
TI  - [Diabetes mellitus in pregnancy].
AB  - The authors highlight some aspects of diabetes mellitus that complicate
      pregnancy. Several complications, e.g. hypoglycaemia, hyperglycaemia and
      macrosomia are described briefly. Macrosomia can be diagnosed by ultrasound
      examination, which should be performed every other week from the 24th week of
      gestation. Accelerated abdominal circumference (> or = 1.2 cm/week) between 32
      and 39 weeks and excess thickness of soft tissue over the proximal humerus of the
      foetus after the 32nd week (> 13 mm at term) may imply development of macrosomia.
      The elevated risk related to adiposity and poor metabolic control can be avoided
      by intensive treatment. Intensive metabolic treatment can also reduce the
      frequency of preeclampsia and polyhydramnion. Ketoacidosis and intrauterine
      foetal death may be consequences of poor diabetic control. The authors discuss
      infectious problems, some aspects of treatment, e.g. risk of preterm delivery,
      dietary treatment and insulin, indications for delivery and various neonatal
      problems.

PMID- 9019849
TI  - [Pregnancy in diabetes].
AB  - The authors review various aspects of gestational diabetes, including definition,
      screening, diagnostic procedures, complications (hypertension, macrosomia),
      clinical evaluation (ultrasound, non-stress test), treatment (diet, insulin),
      indications for delivery and neonatal aspects (hypoglycaemia, hypocalcaemia).
      Complications can be reduced by intensive dietary treatment and insulin. If the
      gestational diabetes is regulated well the woman can wait for spontaneous birth
      at term. In the case of pregnant women with less than optimal regulated diabetes,
      however, or with complications such as hypertension, macrosomia, previous
      stillbirth, labour can be induced preterm by local administration of
      prostaglandin or infusion of oxytocin. Physical training and weight reduction
      should be instituted to avoid later development of type II diabetes mellitus.
      There is still some uncertainty about different aspects of gestational diabetes.

PMID- 9019850
TI  - [Maternal diabetes--normalized perinatal mortality, but still high fetal growth].
AB  - Studies suggest that maternal diabetes can cause both placental insufficiency and
      exaggerated foetal growth. Pregnant mothers with diabetes have suffered high risk
      of losing their child. Data from the Medical Birth Registry of Norway show a
      decrease in the still birth rate from 16th week of gestation from 115.7 per 1,000
      in 1967-75 to 12.8 in 1986-92 in the diabetes groups. The relative risks were 7.8
      and 1.4 respectively for the two time periods. The early neonatal mortality rate
      decreased correspondingly. The proportion of Caesarean sections in mothers with
      diabetes, and the proportion of children with low birth weight or born
      prematurely also increased in the diabetes group. However, children in the
      diabetes group were on average still as big at gestational age in the most recent
      period as in the first period. Our data suggest that the improved metabolic
      control of maternal diabetes has reduced the occurrence and degree of placental
      insufficiency, with inherent decreases in mortality and risk of complications,
      but without reducing the foetal growth-stimulating effect of maternal diabetes.

PMID- 9019851
TI  - [Ultrasonography and neuropathological findings in premature infants].
AB  - At most maternity units all premature infants are investigated by cranial
      ultrasonography as a routine. We examined the correlation between autopsy
      findings and ultrasound examination in 30 premature newborn. The ultrasound
      examination demonstrated bleeding in 17 (65%) of the 26 cases where autopsy had
      revealed bleeding. In these 17 patients good correlation was found between the
      degree of bleeding in the two examinations (ultrasonography and autopsy). In ten
      patients autopsy showed periventricular leucomalacia, but ultrasonography showed
      this condition in only two of these. In five cases bleeding made the examination
      and interpretation of the ultrasound findings difficult. In three patients
      ultrasonography was thought to be normal, while autopsy demonstrated
      periventricular leucomalacia.

PMID- 9019852
TI  - [Nevus flammeus in small children treated pulsed dye laser].
AB  - We report the results of treating 30 children less than 7.5 years old for port
      wine stains of the face and neck using pulsed dye laser with a wave length of 585
      nm. The children were given a general anaesthetic. In five children the stains
      disappeared completely and in 21 there was marked improvement (> 75% lighter).
      The younger age group, 7 months to 4 years, required fewer treatment sessions
      (mean 3.7) than the older age group, 4 to 7 years (mean 5.1 sessions), indicating
      the benefit of early treatment. No side effects were seen except for transient
      hyperpigmentation.

PMID- 9019853
TI  - [Growth hormone deficiency in adults].
AB  - Growth hormone (GH) has been in clinical use for almost 40 years to promote
      linear growth in growth hormone deficient children. Treatment has usually been
      stopped after the epiphyseal plates have fused or when the person reaches a
      proper height. Previously, GH replacement therapy in adults was not deemed
      clinically indicated. GH-deficiency in adults is now accepted as a clinical
      entity, manifested by cardiovascular dysfunction, dyslipidemia, reduced capacity
      for exercise and muscular weakness, altered body composition, increased
      prevalence of osteoporosis, and impaired psychological well-being. The treatment
      of adults used to be unrealistic, because of the limited supply of human
      pituitary-derived GH. Moreover, the risk of transferring Creutzfeldt-Jakobs
      disease led to a stop in the therapeutic use of pituitary GH preparations. The
      availability of recombinant human prion-free GH has made replacement therapy
      possible in GH-deficient adults. In this review, the GH deficiency syndrome in
      adults is described, together with the results of recent clinical studies of GH
      replacement treatment in adults.

PMID- 9019854
TI  - [Sexual abuse of boys. Examples of a group-oriented treatment].
AB  - Although the sexual abuse of boys is much less written and talked about than the
      sexual abuse of girls, it is thought that one of three victims of abuse is a boy.
      This article sums up the symptoms and reactions seen in male victims. Whereas
      women usually react with depression and guilt, men react more with anger.
      Psychosomatic symptoms are often seen, as well as sexual problems such as
      homophobia or exaggerated masculinisation. As many as 30-50% of male rapist and
      child molesters have been molested as children. This makes it important to
      establish a therapeutic dialogue with these men about what they have been
      through, so as to avoid the development of such behaviour if possible. Experience
      from the treatment of male adults who were sexually abused in childhood is
      described, and placed in relation to the existing literature on the subject.

PMID- 9019855
TI  - [Negative reports on oral contraceptives--increased number of interrupted
      pregnancies].
AB  - The reports on a higher risk of venous thromboembolism associated with third
      generation oral contraceptives (OCs) received a great deal of media attention in
      Norway. The Norwegian Medicines Control Authority recommended restricting the use
      of third generation OCs. The sale of the only third generation OC in Norway
      decreased by 73%. The total sales of OCs also decreased by 10%, however, despite
      a recommendation to change drug rather than stop using OC. During the first six
      months of 1996, the number of legal abortions in 11 hospitals covering 60% of all
      legal abortions in Norway increased by 297, or 7%, compared with the same period
      in 1995. A continuous downward trend in the number of legal abortions during the
      period 1990-95 has been broken, and replaced by an increase, which could
      represent a greater risk to women's health than a few cases of venous
      thromboembolism.

PMID- 9019856
TI  - [Surveillance of the HIV-epidemic in Norway].
AB  - Surveillance of HIV infection and AIDS is still a cornerstone in the efforts to
      prevent spread of HIV in Norway. The surveillance system aims at measuring the
      incidence and prevalence of HIV infection in the country. We describe the
      development of the surveillance from 1983 until 1996 based on the National
      Notification System for Infectious Diseases. New cases of HIV infection are
      reported anonymously but cases of AIDS are reported with name. Key information on
      each case includes age, gender, residence and the most likely time, place and
      route of transmission. The notification system is supplemented by screening of
      pregnant women, military recruits and blood donors, and by surveys of the number
      of tests performed, and other information. The information is analysed regularly,
      interpreted and communicated to the health services and the public.

PMID- 9019858
TI  - [The HIV-epidemic among homosexual men in Norway].
AB  - Up to 1996, 592 men had been reported as having homosexually acquired HIV
      infection in Norway (population 4.3 million). 295 of these had developed AIDS and
      242 had died from AIDS. Although HIV testing is common practice among homosexual
      men in Norway, we estimate that 100-200 HIV infected homosexual men have not been
      diagnosed as yet. HIV spread rapidly among homosexuals in Norway in the early
      1980s. The annual incidence peaked in 1985, at 70-100 cases, and has since
      remained at 40-50. In our opinion the initial decrease in incidence was due
      mainly to dissemination of information by the gay community itself, led by
      pioneering gay health workers. The stable incidence during the last decade is
      disappointing, however, considering the vast resources used for prevention. A
      major challenge in HIV prevention in Norway towards the year 2000 is to bring
      down the incidence among homosexual men.

PMID- 9019859
TI  - [The HIV-epidemic among drug addicts in Norway].
AB  - Up to 1996, 368 persons in Norway (population 4.3 million) had been reported as
      being HIV-infected because of intravenous drug use. 72 of these had developed
      AIDS and 59 had died from AIDS. HIV-testing is very common among drug users in
      Norway and new cases are rarely detected at treatment centres or at autopsy. Some
      15-30 cases may still be undiagnosed. HIV spread very rapidly among drug users in
      Norway in 1984 and 1985, by around 100 new cases per year. Since then, the annual
      incidence has decreased from 30-40 cases in 1986 to 10-15 in 1995. Although the
      drug users seldom shared syringes even before the advent of the HIV epidemic, we
      believe that the public rehabilitation programmes, needle exchange programmes and
      health information have contributed to control HIV in this group. We expect an
      annual incidence of 10-15 cases the next five years.

PMID- 9019857
TI  - [The HIV-epidemic in Norway 1996--mainly heterosexual transmission].
AB  - Up to 1996, a total of 1,537 individuals had been reported as having HIV
      infection in Norway (population 4.3 million). 511 of these had developed AIDS and
      410 had died from AIDS. 223 persons had acquired HIV heterosexually. Less than a
      fifth of these had acquired the infection from persons who themselves had been
      infected with HIV heterosexually in Norway. Named testing of pregnant women,
      recruits and blood donors confirms the limited spread of HIV. We estimate that
      the annual incidence of heterosexually acquired HIV infection has remained at 20
      30 for the last ten years. Earlier prognoses for the epidemic in Norway were
      grossly erroneous, mainly owing to lack of knowledge about the factors
      determining the spread of HIV. Given the low rate of transmission of the virus
      and the sexual behaviour of Norwegians, there was never any real danger of a
      large heterosexual HIV epidemic in this country. The future efforts to combat the
      epidemic should focus on maintaining features that make Norwegian society less
      vulnerable to HIV.

PMID- 9019861
TI  - ["Non-insulin-dependent" diabetes--an antithesis? Patients with type 2 diabetes
      should be treated with insulin early in the course of disease].
AB  - There is disagreement concerning the treatment of type 2 diabetes; i.e. whether
      the patient should be given antidiabetic drugs or insulin. However, the peroral
      drugs either increase insulin production by stimulating the beta cells, diminish
      gluconeogenesis or increase the patient's sensitivity to insulin, i.e. they
      enhance a relative effect of insulin. The effects of these drugs diminish after
      some time and they have to be replaced by insulin. Therefore, type 2 diabetes
      should not be characterized as non-insulin dependent. When dietary intervention
      and physical exercise no longer have an effect on the blood sugar these patients
      should be given insulin, especially because this can postpone the development of
      microangiopathic lesions.

PMID- 9019862
TI  - [Protectiopn against pneumococcal disease].

PMID- 9019863
TI  - [Seroxat combined with Meravean--increased risk of hemorrhage?].

PMID- 9019860
TI  - [A case of sexual abuse with several victims in a small municipality. A
      cooperation project between health services].
AB  - This article describes the management of an extensive case of sexual abuse in a
      small Norwegian community. The victims were adult men who had been exploited in
      childhood and adolescence by the same abuser. A demand for support was addressed
      to the health services when these men realised as adults that they shared this
      experience. The community health service and the psychiatric department decided
      to arrange psycho-educative meetings in the community centre. Victims, their
      families and local professional helpers were invited. The meetings gave general
      information about sexual abuse, early and late symptoms and the treatment
      facilities available locally. In one facility a psychiatrist and a general
      practitioner led a treatment group together. Five of the victims took part in
      this group. Fortunately, this case never reached the public press. Cooperation
      between specialist and community health services in managing such cases is
      regarded as essential.

PMID- 9019864
TI  - [Psychology and behavioral biology--why make it difficult?].

PMID- 9019866
TI  - [Strengthening of social medicine].

PMID- 9019867
TI  - [The Nobel Prize in physiology and medicine 1996. What are we going to do with
      tissue typing?].

PMID- 9019865
TI  - [A system of listed patients and tasks of social medicine].

PMID- 9019868
TI  - [How do we perceive the risk?].

PMID- 9019869
TI  - [What is a writer?].

PMID- 9019870
TI  - [Height: healthy, strong and sexy?].

PMID- 9019871
TI  - [Minor head injuries in sport. Occurrence, management, sequelae and prevention].
AB  - Approximately 10% of all head injuries are caused during sport and about 10% of
      all sport-related injuries are head injuries. Most of these are minor head
      injuries. Many sports involve risk of repeated head injury. The classic punch
      drunk syndrome in boxers reflects severe chronic traumatic encephalopathy. Recent
      research shows that repeated head injury can entail encephalopathy also in other
      types of athletes. They may experience symptoms such as headache, dizziness,
      irritability, memory deficit and concentration deficit. Neuropsychological
      testing reveals such cognitive deficits as impaired memory and attention, and
      reduced speed of information processing. Persistent sequelae can be prevented by
      correct management in the acute stage, appropriate follow-up, and prevention of
      repeated head injuries.

PMID- 9019872
TI  - [Religious affiliation and mental health--is there a connection? Health survey in
      Finnmark 1990].
AB  - The Finnmark Health Study in 1990 included questions on both mental health and
      religious affiliation. 7,633 individuals were invited to take part in the study,
      and 4,387 (58%) answered the question about religious affiliation. Members of the
      Norwegian Church (Lutheran Evangelical) had the highest score on all mental
      health variables. The group without any connection with a religious organization
      (non-members) contained highest proportion of persons who were not content with
      their life (20%) and the highest proportion who had coping problems (11%). Non
      members and members of the "Laestadianer" spiritual movement showed the highest
      proportion with insomnia (36%). The proportion using psychotropic drugs was
      highest among the members of the "Laestadianer" spiritual movement (13%), which
      also contained the highest proportion reporting low global health. Owing to its
      cross-sectional design, the present study is unable to establish the causal
      direction of the association between religious affiliation and mental health.
      Various aspects of some religious beliefs and practices can probably cause mental
      health problems, and persons with mental health problems may be attracted to
      certain religious groups. Only future follow-up studies can untangle and quantify
      these possible causal associations.

PMID- 9019873
TI  - [Possessed! Some historical, psychiatric and curent moments of demonic
      possession].
AB  - Being possessed by demons or evil spirits is one of the oldest ways of explaining
      bodily and mental disorders. The article briefly mentions some contributions from
      other disciplines, but considers in particular psychiatry's and medicine's
      approach throughout history. During the middle ages of Europe possession (and
      witchcraft) was considered just one out of several causes of mental illness.
      Astrological theories prevailed, in addition to the humoral theories of medicine.
      In addition distinctions were made between eccentricity, madness and religious
      visions and revelations. A large number of the alleged witches and possessed
      persons who were burned probably had visible mental disturbances. Today's
      psychiatry does not refer symptoms of possession to any specific category, but
      usually classifies this as some kind of psychotic disturbance of thought.
      Exorcism of evil spirits by Jesus Christ is described often in the Gospels.
      Possession was the only "available" concept for a bundle of neuro-psychiatric
      disorders: dissociative states, psychoses and epilepsy. To day, the terminology
      and "diagnostic" principles have been taken over by fundamentalistic groups, who
      practise exorcism on persons with (probably) minor mental problems and symptoms.
      The author criticises this activity.

PMID- 9019874
TI  - [Asklepius. The compassionate god].
AB  - The ancient Greeks had many gods of healing, but none other achieved the popular
      esteem and adoration as Asklepios, son of Apollo, pupil of the centaur Cheiron.
      People made pilgrimages to the temples of Asklepios. The great Galenos himself
      reports that Asklepios appeared to him in a dream, bidding him to become a
      physician. For more than 800 years Asklepios was looked upon as the ideal
      physician, and after his death became the compassionate god, the friend of
      suffering humanity. The temple medicine of Asklepios was totally different from
      the rational practice of hippocratic physicians. A good doctor, however, needs
      not only a cool brain, but also a warm heart. In order to practice our craft to
      the benefit of our fellow human beings we need inspiration from other sources.
      But, like Sir William Osler (1749-1919) we should not try to mix the oil of
      religion with the waters of science. The last words of Socrates were "Crito, we
      owe a cock to Asklepios". Perhaps sacrificing a cock to Asklepios would be a good
      idea before our next patient enters the surgery?

PMID- 9019875
TI  - [On historical site--the Norwegian Medical Society's new headquarters].
AB  - The Norwegian Medical Association has built a new headquarters in the centre of
      Oslo. The site is one of the very oldest in the city and has a long history
      because of its many different functions--it has been a cemetery, riding ground,
      church site and petrol station. The interesting history of the site is described
      in this article.

PMID- 9019876
TI  - [From barber-surgeons' guild to medical association. A 400th anniversary].
AB  - The barber-surgeons' guild in Bergen was founded on 17 January 1597. For nearly
      250 years this was the only "medical association" in Norway. The guild
      disappeared with the death of its latest master, Christian Wilhelm Wisbech (1740
      1822). However, only nine years later his son, Christian Wisbech (1801-69),
      founded the Medical Association in Bergen. The barber-surgeons were craftsmen who
      got their education by apprenticeship. They were the medical practitioners of
      their times. Their empirical knowledge was more in touch with real life than was
      the medicine taught by the professors. This paper describes the barber-surgeons'
      education and work, including their conflicts with other craftsmen and doctors.
      During the 18th century the barber-surgeons' education was improved, and
      eventually was given full academic status.

PMID- 9019877
TI  - [Medical and natrual scientists behind the museum which became the University of
      Bergen].
AB  - The University of Bergen celebrated its 50th anniversary in 1996. The University
      was built on an earlier institution, the Bergen Museum, founded in 1825. From
      1880 until the beginning of this century the Museum gradually developed into an
      institution for research and higher education. The article describes work done by
      some of the key persons involved in this process, mainly medical and natural
      scientists. In particular, their international relations and ability to
      cooperative with other scientists were crucial factors in establishing the
      pillars of the later University of Bergen. Today, the University of Bergen has
      nearly 18,000 students and seven faculties, and is a highly internationalised
      institution.

PMID- 9019878
TI  - ["Gentlemen, this is not a humbug". The 150th anniversary of anesthesia].
AB  - On 16 October 1996 it was 150 years since William T.G. Morton performed the first
      successful demonstration of ether anaesthesia in the Massachusetts General
      Hospital, Boston, USA. Controlling the pain caused by surgery had been a problem
      for a long time. In fact, many chemical agents with pain relieving properties
      were recognized before they were used in practice. Morton started systematic
      studies on the anaesthetic effects of ether and convinced the medical world of
      the importance of pain free operations through his demonstration of ether
      inhalation. The news about ether anaesthesia spread around the world very
      quickly. The first ether anaesthesia administered in Norway took place at
      Rigshospitalet in Christiania on 4 March 1847. The first death from anaesthesia
      in Norway occurred in 1852. This article presents some aspects of both the
      Norwegian and international history of anaesthesia.

PMID- 9019879
TI  - [Henri Beckquerel's discovery of radioactivity, and history of nuclear medicine.
      100 years in the shadow or on the shoulder of Rontgen].
AB  - In 1896 Henri Becquerel discovered that uranium emitted penetrating rays similar
      to X-rays. His finding started a series of discoveries that were rewarded with
      numerous Nobel prizes. Marie and Pierre Curie found that thorium was radioactive
      too, and discovered and described two new elements, polonium and radium. They
      also found that radioactive radiation could be separated into alpha, beta and
      gamma rays. In 1993 their daughter Irene Joliot-Curie and her husband Frederic
      Joliot managed to produce radioactivity artificially by bombarding atomic nuclei
      with alpha particles. Enrico Fermi did likewise, but bombarded the nuclei with
      neutrons. In the cyclotron invented by Ernest Lawrence, radioactive isotopes were
      produced by proton bombardment. The ability to produce radioisotopes of different
      elements initiated a variety of tracer studies in biology and medicine. The
      number of studies increased exponentially when the nuclear reactor in Oak Ridge,
      US, was opened for radionuclide production in 1946. This article summarises the
      history of the application of radionuclides in science and medicine
      internationally and in Norway until now.

PMID- 9019880
TI  - [The isolation hospital on Katten in Bergen].
AB  - In 1864 the Board of Health in Bergen, Norway, feared that an epidemic of
      smallpox might break out in the city. A house on the bastion Katten (Norwegian
      for "the cat") on the Fredriksberg fortress was adapted and made a provisional
      smallpox hospital. Later on it also served as a cholera hospital during a minor
      cholera epidemic in 1873, and as an isolation hospital for patients suffering
      from scarlet fever. The hospital housed only five to seven patients and two
      nurses. The doctor and hospital orderlies were isolated in an adjacent house. The
      Board of Health presented several plans for enlarging the hospital. Only in 1891
      was the hospital on Katten replaced by a new and larger isolation hospital in
      another part of the city (Sandviken). At first, the Board of Health introduced
      rigid isolation regulations which were difficult to satisfy. When the pathogenic
      bacteria were discovered and the spread of infection was better understood, the
      view on isolation and other measures became more rational.

PMID- 9019881
TI  - [Jean Martin Charcot and his controversial research on hysteria].
AB  - Jean Martin Charcot (1825-1893) is known as the founder of neurology in France
      and was one of the most versatile medical researchers of his times. At the climax
      of his career in the Salpetriere in Paris he began to study the phenomenon of
      hysteria. Hysterical symptoms were very common in the late nineteenth century in
      Europe and were looked upon as a challenge to medical science. By means of
      accurate observation, Charcot managed to describe the distinct features of
      hysteria. The disease became an accepted medical entity and patients were less
      often regarded as simulators. Charcot presumed that the disease had a physical
      cause, and tried to prove this by means of patho-anatomical studies and later by
      experiment, with help of hypnosis. Charcot's despotic personality, the
      extraordinary circumstances at the Salpetriere and the hysteric patients formed a
      fascinating setting that gives exemplary insight into the non-linear progress of
      medical science.

PMID- 9019882
TI  - [Eilert Storen, district medical officer in Meldalen].
AB  - Eilert Storen (1860-1929) was the district medical officer in an inland community
      in mid-Norway for 40 years. He saw the medical problems in his area in a
      perspective beyond the patients' immediate needs. Based on his own observations
      he published four major medical works; two on tuberculosis, one on nutrition and
      one on lues. In addition he was the author of several singular publications on
      various topics, and some case reports. He was a pioneer in recording the cultural
      history of his community and produced more than 40 publications in this field.
      The local museum was founded on the basis of his collections of antiquities etc.
      He was also politically active and had a seat on the municipal council, and held
      several public commissions.

PMID- 9019883
TI  - [Roald Amundsen--a study of personality].
AB  - Roald Amundsen is the most famous of the Norwegian polar explorers. His ancestors
      came from a group of islands south-east of the Oslofjord. From being fishermen
      and sailors, they progressed to becoming captains and shipowners in the course of
      two generations. Amundsen's father, Jens, stayed at sea until his ship went down
      with all the crew. Roald was 14 years of age at the time, the youngest of four
      competing brothers. Jens had left the close-knit local family community before
      that, and bought a flat in the capital, Oslo, so that his sons could get a better
      education. Roald's mother wanted him to study medicine. He did as she wished for
      a time, but was not at all interested. When his mother died, he abruptly left the
      university and went to sea, which had been the tradition in his family for
      decades. As a young boy he was an admirer of Sir John Franklin and his explorers
      of the Northwest Passage. Fridtjof Nansen became his ideal. The biographies about
      Roald Amundsen are very diverging--some hold him a hero, others reflect a
      strongly critical attitude. Here, the author tries to define his personality and
      places him firmly within the narcissistic domain. His tendency to seek the
      company of married women, but to take immediate flight when they really became
      interested reflects an Oedipus complex from before puberty. The tragic death of
      his father, the sea captain, may have been a supposition; puberty can be seen as
      a period of coping with ambivalence towards an earlier idealized father. His
      genius combined ambitious goals with a sharp eye for details as regards the
      equipment used in his expeditions. In his travels in the Arctic and the Antartic
      he was driven forward by the energy of the nation. His heroic death, trying to
      save his earlier "enemy", Nobile, was probably caused by an urge for self
      destruction.

PMID- 9019884
TI  - [Martin Luther's somatic diseases. A short life-history 450 years after his
      death].
AB  - The article contains a short life-history of the religious reformer Martin Luther
      (1483-1546) with main emphasis on his many somatic diseases. The list comprises
      varicose ulcer, angina pectoris with anxiety, obesity, hypertension arterialis,
      Meniere's disease with vertigo, tinnitus and fainting fits, gastralgia,
      constipation with anal ulcers and haemorrhoids with bleeding, urolithiasis,
      arthritis urica, Roemheld's syndrome, and cataract in one eye. Mentally he had a
      manic-depressive cast of personality, and a tendency to emotional lability. In
      spite of this he had an enormous capacity for work.

PMID- 9019885
TI  - [When you get a gut feeling...].
AB  - Functional disorders like functional dyspepsia, irritable bowel syndrome and non
      cardiac chest pain are common diseases. No organic lesion can be found to explain
      the often disabling symptoms. Typical features of functional dyspepsia are
      anxiety, depression, neuroticism, visceral hypersensitivity, abnormal autonomic
      nerve activity with a weak vagal and an higher sympathetic tone, and impairment
      of gastric accommodation. This last abnormality may be due to weak vagal tone and
      poor adaptive relaxation of the proximal stomach. The degree of dysfunction of
      the variables is sometimes correlated, suggesting that the pathogenetic factors
      may be interacting in a viscious circle. Medical therapy is often unsuccessful,
      but extensive research in the field has given better insight into the
      pathophysiological mechanisms, giving hope for new therapeutic modalities,
      including visceral analgesics. It may still be difficult, however, to distinguish
      organic from functional disorders. Reliable tests of visceral hypersensitivity
      would be helpful in this respect.

PMID- 9019886
TI  - [Medical publishing--dissemination of knowledge or personal promotion?].
AB  - Over time an evolution has taken place in the nature of medical publishing. From
      being more-or-less exclusively channels for professional information to
      clinicians, medical journals have become tools in the process of qualifying
      researchers. Bringing credits to authors has become one of the main tasks of
      scientific publishing. This evolution can be described as a shift from a main
      focus on the reader as the recipient of information (reader-orientation) to
      greater emphasis on the author, who gets merits for publishing scientific papers
      (author-orientation). The scientific community does not live up to the
      international guidelines, which require substantial contributions in order to
      obtain authorship credits. The result has been author inflation and honorary
      authorship. The concept of authorship has changed, which may imperil the
      integrity of the scientific article. Increasing consciousness and changing
      attitudes are needed among researchers, medical schools and granting agencies. A
      stricter and more traditional definition of authorship should be established.

PMID- 9019887
TI  - [Life expectancy in Norway. An international perspective--causes of death].
AB  - We have shown before that Norway is experiencing an unfavourable trend in life
      expectancy compared with Japan, France and several other OECD countries. In this
      article, we discuss the cause-specific differences in mortality that explain
      these contrasts. Heart infarction is the predominant cause of death in Norway,
      with a mortality five times higher than in Japan and three times higher than in
      France. Both Norway and France have three times higher mortality rates for breast
      cancer than found in Japan, and the mortality rate for cervical cancer is twice
      as high in Norway as in the two other countries. Norwegian women show a mortality
      rate for lung cancer that is twice as high as that of their French sisters.
      Suicide among young Norwegians is a rapidly growing problem, and twice as common
      among Norwegian men aged 20-24 than among Japanese men of the same age. We
      challenge the health authorities and the specialists in the relevant fields to
      reflect again on their preventive strategies, in light of these contrasts.

PMID- 9019888
TI  - [May old age give impulses to an improved physician's role?].

PMID- 9019889
TI  - [Cohort studies--a Norwegian discovery? An unexpected glimpse from the early
      years of epidemiology].

PMID- 9019890
TI  - [Scientific qualification and competence assessment].

PMID- 9019891
TI  - [Medical students don't receive enough training in leadership].

PMID- 9019892
TI  - [Polycythemia on the prophetess' stool].

PMID- 9019893
TI  - Proceedings of the 15th annual meeting of the American Society of Transplant
      Physicians. Dallas, Texas, May 26-30, 1996.

PMID- 9019894
TI  - [The structural and functional characteristics of the dolichol cycle enzymes].
AB  - The literature and the authors' our data on the biosynthesis of a dolichol
      derivative Dol-PP-GlcNAc2Man9Glc3, involved in protein N-glycosylation in the
      endoplasmic reticulum (ER) of the eukaryotic cells, have been summarized and
      analysed. The structural and functional characteristics of dolichol-coupled
      enzymes, catalyzing biosynthesis of Dol-PP-GlcNAc2Man9Glc3, are considered. It is
      shown that the dolichol cycle enzymes, in conformity with their structural
      peculiarities and ER membrane topology, can be divided into three groups having
      the common evolutionary origin. Possible mechanisms of the dolichol derivative
      translocation through membrane is discussed. A conclusion is made about formation
      of multicomponent complexes by dolichol-coupled enzymes. These complexes secure
      functional co-ordination of the enzymes.

PMID- 9019895
TI  - [An ultrastructural study of the apical cytoskeleton of the epithelial cells in
      the frog bladder with an ADH-dependent and an ADH-independent increase in osmotic
      permeability].
AB  - Immunocytochemical methods of electron and confocal microscopy were applied for
      studying the primembrane actin cytoskeleton in the frog urinary bladder granular
      cells, following the two actions: under the increased vasopressin-induced water
      permeability, and following autacoid removal by multiple changes of the Ringer
      solution around the serosa. In both cases similar changes have been revealed in
      the structure of the apical cytoskeleton and, in addition, a decrease in the
      density of its actin filament distribution was noticed.

PMID- 9019896
TI  - [The glycogen-forming function of the hepatocytes during the regeneration of the
      cirrhotic rat liver after a partial hepatectomy].
AB  - The paper deals with a cytofluorimetric study of the content of glycogen and its
      fractions as well as with a microbiochemical study of glucose-6-phosphatase,
      glycogen phosphorylase, and glycogen synthase activities in the rat liver
      parenchyma cells in norm, in the course of cirrhosis development, and at various
      time intervals after the end of the carbon tetrachloride (CCl4) poisoning and
      after a partial hepatectomy (PH). Serial liver biopsies were obtained from each
      animal prior to CCl4 action (control), 6 months after a chronic intoxication with
      CCl4 inducing liver cirrhosis, and then 3 and 6 months after the end of CCl4
      poisoning of rats, and after the cirrhotic liver PH. It has been shown that the
      total glycogen content in the cirrhotic liver hepatocytes increases by 1.4-1.5
      times, compared with control, however, it returns to the norm 6 months after the
      PH. The glycogen labile fraction (LF), that accounts for 85% of the total
      glycogen, amounted to 65% in liver cirrhosis. The most striking changes in liver
      cirrhosis occurred in the glycogen stable fraction (SF) which rose by 3.9 times
      in the cirrhotic liver. The LF/SF ratio returned to the norm 6 months after the
      PH. The activity of glucose-6-phosphatase fell by 2.7 times in the liver
      cirrhosis; its activity after the PH initially increased, then decreased again to
      reach 6 months after the PH the same level as in the cirrhotic liver before the
      PH. The activities of glycogen phosphorylase and glycogen synthase returned to
      the normal level 6 months after the PH. The results of the current study make it
      possible to conclude that the PH of the cirrhotic liver facilitates only a
      partial restoration of the glycogen forming function of hepatocytes.

PMID- 9019897
TI  - [The genotoxic effect of ciprofloxacin on cultured cells from the kangaroo rat
      kidney and on skin fibroblasts from the Indian muntjac].
AB  - The genotoxicity of an antibiotic ciprofloxacin (CF) in doses of 10, 25, 50 and
      100 mkg/ml under its short-term (6-48 h) and long-term (15-30 days) action on
      sublines of Rat kangaroo kidney, NBL-3-11, and Indian muntjak skin fibroblasts
      has been studied. The emergence of genotoxic effect depends on the dose and time
      of ciprofloxacin action on both the sublines, but the degree of this effect does
      not depend on these parameters directly. Ciprofloxacin exerts no influence on
      cell distribution for chromosome number in subline NBL-3-11, and increases
      heterogeneity of this parameter in the subline of Indian muntjac skin fibroblasts
      in 30 days after its addition in doses of 25 and 50 mkg/ml. The degree of
      increase of chromosomal aberrations in the subline of Indian muntjak skin
      fibroblasts was in average 1.5 times more than in NBL-3-11 in all examined
      variants compared to the control. The minimum antibiotic dose that induced
      chromosomal aberrations was 25 mkg/ml in the subline of NBL-3-11 under a short
      term action and 50 mkg/ml under a long-term action. For the subline of Indian
      muntjac skin fibroblasts the minimum inducing dose was 50 mkg/ml irrespective of
      the duration of action, except the case of 15 days, when the number of dicentrics
      increased still at 25 mkg/ml. In both sublines with the duration of ciprofloxacin
      action within 6-24 h the replacement of chromatid aberrations by chromosomal
      aberrations occurred. Under a long-term ciprofloxan action differences in types
      of chromosomal aberrations were discovered: for subline NBL-3-11 these were
      mainly chromosomal breaks; in the case of muntjac cells both chromosomal breaks
      and dicentrics (telomeric associations) occurred. The preferential involvement of
      some chromosomes in dicentric formation was observed. In cells of the muntjac
      subline, unlike NBL-3-11, the sensitivity of individual chromosomes to
      ciprofloxacin-induced breaks differed from that to spontaneous breaks. In both
      the sublines ciprofloxacin induces chromosomal breaks mainly in definite regions
      of chromosomes. Possible reasons of differences between the examined sublines
      towards the character of chromosomal instability are discussed in addition to the
      role of dicentrics as a proposed adaptation of cells to unfavourable factors of
      the environment.

PMID- 9019898
TI  - [A comparison of the patterns of delayed cell death after exposure to genotoxic
      agents].
AB  - A lot of data have been provided on different types of cells showing that
      ionizing radiation induces a hereditable genome instability, which may lead to
      mutations chromosome aberrations and cell death. In this paper we studied delayed
      death, proliferative activity, sensitivity to genotoxic agents to progeny of HeLa
      and LL cells following treatment with ionizing radiation, cis-platinum,
      methylhydroxurea which induce different types of lesions with different rate of
      repair. The rate of death of the progeny, dynamics of the clonogen ability
      recovery, growth rate recovery after the treatment with genotoxic agents are
      different. We have supposed that the delayed cell death may be associated with
      different types of hereditable lesions.

PMID- 9019899
TI  - [The nature of macrophage functional heterogeneity exemplified by Fc receptors].
AB  - It is known that functional activity of macrophages (Mph), adhesion and
      phagocytosis, depends on the local concentration of Fc receptors (Fc gamma R) on
      the cell surface. Fc gamma R may have a random distribution on cell membrane or
      form clusters of different sizes. This process depends on the local activity of
      microfilaments that, in its turn, reflects peculiarities of macrophage
      microenvironments. One may conceive that the number of opsonized erythrocytes
      (OE) subject to adhesion (engulfing) to separate Mph depends on the amount of
      active centres on the cell surface and their activity. The structures, such as Fc
      gamma R clusters, phagosomes and others, in whose formation numerous components
      of Mph (cell skeleton, microvesicles, signal receptive system and others) are
      involved, are arbitrarily called the structural functional units (SFU). Thus, we
      used two parameters: the average number of SFU per Mph in population, and the
      average activity of SFU instead of a generally accepted number of OE per Mph. The
      number of SFU per Mph can be 0, 1, 2 etc., and one SFU may bind (engulf) 0, 1, 2
      etc. EA. For the assessment of the parameters, the approximation of experimental
      histograms by type-A Neyman's distribution was used. To verify the adequacy of
      the model, observations of OE adhesion and phagocytosis in different conditions
      were made. The results show that the parameters of the model fit well the
      biological processes in this system.

PMID- 9019900
TI  - [A simple method for the use of 2-phase polymer systems for the analytical study
      of the cell surface and macromolecules].

PMID- 9019901
TI  - [Clinical aspects of injury to the eye inflicted with gas pistols for self
      defense].
AB  - The clinical picture of an injury inflicted with gas pistols represents
      polymorphous changes and severe injury to the organ of vision, involving not only
      the anterior segment, but the deep structures as well. Analysis of the status of
      the damaged eyes and the mechanism of injury permitted us to distinguish 3
      clinical groups in terms of the intensity of exposure to this or that factor: 1)
      chemical burn of the cornea and conjunctiva (65 patients); 2) chemical burn with
      elements of thermal involvement and impregnation of tissues with particles of
      gunpowder that failed to burn and slight or medium-severe contusion of the
      eyeball (31 patients): and 3) severe thermochemical burn with grave contusion of
      the eyeball, sometimes with rupture of membranes (6 patients). Hence, we may
      conclude that the consequences of using gas weapons differ from those described
      in the Status of Gas Weapons Application and in advertising materials by a much
      greater severity, and in 11.7% cases such injuries led to complete irreversible
      loss of vision. Obviously the shortest distance from which it may be allowed to
      shoot from gas pistols should be increased to 1 meter.

PMID- 9019902
TI  - [Epidemiological characteristics and risk factors of sympathetic ophthalmia].
AB  - Clinical factors of risk of sympathic ophthalmia (SO) determined by the type of
      injury, methods of surgical and drug treatment, and supported by published data
      were distinguished as a result of treating 158 patients with SO at the Helmholts
      Research Institute of Ophthalmic Diseases from 1965 to 1994. Special attention is
      paid to the possibility of SO development during steroid therapy of posttraumatic
      uveitis. In such cases SO develops in case of 1) sudden discontinuation of a
      course of steroids; 2) discontinuation of a short course of steroid therapy in
      the presence of persisting signs of posttraumatic uveitis; and 3) in surgery on
      the traumatized (operated on) eyes and low steroid doses.

PMID- 9019903
TI  - [Experimental use of a cytostatic and a corticosteroid on a collagen implant in
      surgery for glaucoma].
AB  - Clinical and morphologic studies of local application of a cytostatic (5
      fluorouracyl) and a corticosteroid (dexasone) on a collagen implant in filtration
      surgery for glaucoma were carried out. The velocity of regression of filtration
      cushion (FC), intraocular pressure, and local connective tissue reaction after
      sinusotrabeculectomy with collagen implant were examined in 30 rabbit eyes.
      Impregnation of the implant with the preparations prolonged 3-fold the period of
      FC existence in comparison with the control. The cytostatic 1.5 to 2 times
      reduced the inflammatory infiltration and fibroblast proliferation in the wound,
      this creating optimal conditions for the formation of functionally competent
      discharge canals.

PMID- 9019904
TI  - [Early age-specific changes in the accommodation volume].
AB  - The nearest and furthest points of clear vision were determined in 475 patients
      aged 6 to 16 years using an AKT-02 device after the optotype of Landolt's ring
      for 0.7 vision acuity. The mean values of accommodation volume for each age group
      were determined. They increase from 9.29 +/- 0.19 diopters at the age of 6 years
      to 12.25 +/- 0.23 diopters at 13, then gradually reduce to 10.0 +/- 0.19 diopters
      at 16. The descending slope of the curve coincides with the curve plotted by S.L.
      Shapovalov, who used the same method for measuring the accommodation volume. The
      volume of accommodation was 0.75 diopters reduced in myopic children in
      comparison with those with emmetropia.

PMID- 9019905
TI  - [Fibrinolytic activity of the lacrimal fluid in disordered choroid circulation in
      patients with arterial hypertension].
AB  - Fluorescent angiographic examination of the choroid and retinal circulation in 43
      patients with arterial hypertension of different origin without signs of
      hypertensive retinopathy with low and normal values of the fibrinolytic activity
      of the lacrimal fluid (FALF) revealed a correlation between disorders of the
      choroid circulation (ischemic zones, delayed time of contrast staining of the
      choroid) and reduction of FALF. The results indicate that a reduction of FALF may
      be regarded as a prerequisite for the development of circulatory disorders in the
      choroid.

PMID- 9019906
TI  - [Immunological studies on cataracts under conditions of exposure to low-dose
      radiation].
AB  - Immunopathological changes were studied in cataract patients chronically exposed
      to low-dose ionizing radiation occupationally or as a result of living in
      districts polluted with radionuclides after the Chernobyl accident. No cellular
      autoimmune shifts were detected in the examinees; humoral autoimmune changes in
      respect of different ocular antigens were revealed. Low-dose ionizing radiation
      was conducive to the formation of thermostable complement-fixing antibodies to
      lens tissues. One of the causes of the production of such antibodies were
      disorders in the helper-suppressor relationships of T-lymphocytes. The studies
      confirm the hypothesis on the possibility of cataract development as a result of
      low-dose exposure.

PMID- 9019907
TI  - [Para-aminobenzoic acid in therapy of experimental keratitis caused by herpes
      simplex virus in rabbits: the therapeutic effect and decrease of infectious
      titer].
AB  - Para-aminobenzoic acid (PABA) in low concentrations exerted an antiherpetic
      effect with a good therapeutic result in rabbits with experimental
      keratoconjunctivitis caused by herpes simplex virus (HSV) (experimental group).
      In group 2 (control) 0.9% NaCl solution was used as placebo. The animals were
      infected by instillation of HSV-1 on the cornea predissected with a bifurcation
      needle. The severity of keratitis was assessed in scores after A. A. Kasparov et
      al. PABA and placebo were administered starting from day 3 postinfection as
      subconjunctival injections and then instillations. In experimental group (5
      rabbits, 10 eyes) the degree of keratitis reduced from 3.0 +/- 0.2 to 1.7 +/- 0.1
      points within the first 4 days. Complete epithelialization was over by day 4.4 +/
      0.4, clinical cure was attained by days 12-13. In control group (6 rabbits, 12
      eyes) erosion of the cornea and severity of keratitis increased from 2.9 +/- 0.07
      to 3.8 +/- 0.2 points by day 4 postinoculation after placebo was started, after
      which it reduced; epithelialization was over by day 8.2 +/- 0.3, clinical cure by
      days 13-14. Infective titer in the cornea was determined in VERO cell culture
      from the degree of virus-induced cytopathogenic effect and expressed in lgTCE50.
      On day 13 this parameter was reliably higher in the control group in comparison
      with the experimental (3.2 vs. 1.8), this confirming the virucidal effect of
      PABA.

PMID- 9019908
TI  - [Definition of the term "complicated cataracts"].
AB  - Cataracts with different risk factors differ in their clinical course. Surgical
      removal of such cataracts requires a differentiated approach to drug therapy in
      the pre- and postoperative periods. On the other hand, surgery, for example, for
      uveal cataracts involves additional manipulations, dissection of synechias or
      more coarse adhesions. The risk of inflammations in the immediate postoperative
      period and of secondary cataracts in remote periods is high in diabetics with
      uveal cataracts. Analysis of published data and our own clinical findings
      permitted us to make the existing classifications of complicated cataracts more
      accurate. We consider that the term "complicated cataracts" should not be
      changed. This patient population includes those for which the factors of risk of
      cataracts are uveitis, myopia, glaucoma, diabetes mellitus, and other diseases
      causing changes in ocular structures, which, in turn, become a risk factor in
      terms of development of complications during and after cataract extraction.

PMID- 9019909
TI  - [Why is the eye round?].
AB  - By an unsophisticated experiment, published data on the anatomy of the eye, wave
      theory of light, and the laws of geometrical optics the author tries to prove
      that a spherical concave screen is the optimal variant of a screen on which
      spherical wave front is projected, formed by a single lens. The shape of the wave
      front and of the concave screen are in complete agreement. Such optical
      imperfections as the field curvature, distortion, coma (partially), and
      astigmatism of the oblique light beams are compensated for. These optical
      drawbacks are undetectable on a concave screen, and hence they are proposed to be
      the shortcomings of a flat screen. The author compares this to a spherical shape
      of the eye, the posterior wall of which represents a concave screen, an
      indisputable fact, and assumes that the before-named optic imperfections are
      completely compensated for in human eye due to concavity of the posterior optic
      wall. Based on the anatomy and practical results of using aspherical refracting
      surfaces in artificial optic devices, the author draws a parallel with the
      anatomical structures of the eye possessing aspherical refracting surfaces in
      order to demonstrate that higher and lower-order spherical aberrations (Zeidel's
      aberrations) are fully compensated for in human eye, as are the position and
      enlargement chromatism. Analysis of published data permitted the author to assert
      that the eye of man is characterized by a method for compensation of spherical
      aberrations, which has no analogs in man-made practice. Hence, the Nature has
      imparted the eye with such a collection of compact, universal, and highly
      effective methods for compensation of optic imperfections, which is not to be
      found in any of the man-made devices of today.

PMID- 9019910
TI  - [Contribution of free-radical reactions of chamber humor to the development of
      primary open-angle glaucoma].
AB  - The level of lipid peroxidation products (malonic dialdehyde) is more than two
      times increased in the anterior chamber humor in patients with far advanced
      glaucoma in comparison with the well-developed stage. The level of the total
      antioxidant activity of humor is reliably lowered. A correlation has been
      revealed between the antioxidant activity of humor and its production. These
      results prompt us to recommend antioxidants for therapy of primary glaucoma.

PMID- 9019911
TI  - [On the role of the posterior hyaloid membrane in the pathogenesis of and surgery
      for proliferative diabetic retinopathy].
AB  - A total of 278 patients subjected to transciliary vitrectomy for proliferative
      diabetic retinopathy (PDR) were followed up. Thirty preparations of epiretinal
      membranes removed in surgery were examined under an optic microscope. Vessels
      newly forming in PDR were found to grow mainly along the external surface of the
      posterior hyaloid membrane; they ceased their growth after its removal. The
      posterior hyaloid membrane is the anatomical object of surgical intervention of
      PDR. The proliferative form of diabetic retinopathy is never seen in the presence
      of a naturally occurring or vitrectomy-induced complete posterior hyaloid
      detachment, that is why if the posterior hyaloid membrane is well detached from
      the retina in the course of operation, panretinal laser coagulation in the
      postoperative period is not recommended.

PMID- 9019912
TI  - [Iridoplasty with silica-dried iris].
AB  - A new method for preserving cadaveric iris, based on the detection of residual
      humidity, is proposed: drying on silica gel. Silicadried iris was tried in 42
      experimental rabbits and clinically used in 13 patients with good results.

PMID- 9019913
TI  - [The effect of Maillard reaction products on enzyme reactions].
AB  - In this article current knowledge about the Maillard reaction in vivo is
      described first, especially the glycosylation reactions of various tissues and
      the identification of different final products and intermediates of Maillard
      reaction. The influence of MRP on digestion is of significant importance. These
      products are absorbed in different ways and are excreted in various amounts.
      Hence, the organism is variably influenced by MRP. The influence of defined MRP,
      of glycosylated proteins and of melanoidins on glycosidases and proteases is
      described. The effects produced depend on the enzyme and on the used MRP.
      Reactive alpha-dicarbonyl compounds play an important role in the organism.
      Further possible reactions of these compounds caused by reductases are discussed.
      The protein structure of enzymes is changed by Maillard reaction. Thereby the
      enzyme activity is influenced by covalent modifications of different amino acids
      and by inter- and intramolecular crosslinking. Finally, the use of enzymes and
      monoclonal antibodies for detection of MRP is discussed.

PMID- 9019914
TI  - [Vitamin E distribution of lipoproteins in patients with coronary heart disease].
AB  - The oxidative modification of LDL could play an important role for the
      development of atherosclerosis. The present study was undertaken to compare the
      concentration of vitamin E in serum and lipoproteins between patients with
      coronary heart disease and a healthy control group. The study included 36 male
      patients with angiographically established coronary three-vessel disease and 32
      healthy volunteers. Cholesterin, triglyceride, LDL-cholesterin, HDL-cholesterin,
      and vitamin E in serum and in lipoproteins were determined. The serum vitamin E
      concentration in the patients group was significantly higher than in controls.
      However, vitamin E was correlated with cholesterin in both groups. The
      distribution of vitamin E in healthy volunteers was LDL 53%, HDL 34% and VLDL
      13%, whereas that in patients was LDL 57%, HDL 26% and VLDL 16%. The level of
      vitamin E in LDL was in the patient group significantly higher and correlated
      with the vitamin E- and the cholesterin-concentration in serum. The ratio vitamin
      E/cholesterin in LDL was in patients discretely lower, whereas the same ratio in
      HDL was higher. The results suggest that also in patients with coronary artery
      disease vitamin E is related to the lipid concentration. The decreased ratio
      vitamin E/cholesterin in LDL could be attributed to the oxidative modification of
      LDL.

PMID- 9019915
TI  - [The effect of different vitamin B6 supplies on the vitamin B6 status
      (pyridoxine, pyridoxal and pyridoxamine) of the liver and the body of lactating
      rats].
AB  - Eighty female Sprague-Dawley rats were fed a semisynthetic diet during gravidity
      which was supplemented with 5 mg vitamin B6 per kg diet. The daily food intake
      was 14 g. During the following lactation the rats were assigned to one of 10
      vitamin B6 treatment groups (0, 3, 6, 9, 12, 15, 18, 36, 360 and 3,600 mg per kg
      diet). The feed was given ad libitum. At day 14 of lactation the rats were
      decapitated. Parameters for determination of the vitamin B6 status were
      concentration of pyridoxine, pyridoxal and pyridoxamine in liver and body
      analyzed by using HPLC. Body was defined without the gastroenteral tract that was
      divided into carcass (extrahepatic compartments without liver) and total body
      (extrahepatic compartments plus liver). The mean weight of liver was 13 g with a
      dry mass of 33%; there was no difference between the treatment groups. The
      vitamin B6 concentration was lowest in rats fed 0 mg vitamin B6/kg diet (5
      micrograms/g fresh matter, FM) and highest in the rats fed 3600 mg vitamin B6/kg
      diet (10.9 micrograms/g FM). The total vitamin B6 consisted on the average of 38%
      pyridoxal and 62% pyridoxamine. This was only changed significantly at the
      highest supplementation level, where 20% pyridoxine were detected instead of
      pyridoxamine. The mean weight of carcass averaged 212 g at a dry matter content
      of 31%. The vitamin B6 concentration ranged in the treatment groups from 0 mg to
      360 mg vitamin B6/kg diet between 2.1 micrograms/g FM and 2.8 micrograms/g FM. It
      was highest in the 3600 mg vitamin B6 treatment group at 7.5 micrograms/g FM. The
      total vitamin B6 consisted of 63% pyridoxal and 37% pyridoxamine. It was only
      significantly affected in the 3600 mg vitamin B6 treatment group, where also
      pyridoxine could be found in the amount of 56%. The results indicate that
      alimentary vitamin B6 supply had more influence on liver vitamin B6 concentration
      than on carcass concentration. Total body concentration is very similar carcass
      concentration, as 95% of vitamin B6 is located there. The suitability of the
      parameters by the evaluation of the vitamin B6 requirement was confirmed the
      comparison of two statistical methods. It is concluded that a vitamin B6 supply
      of 5 to 6 mg/kg diet is necessary to meet the requirements during lactation.

PMID- 9019916
TI  - [The effect of alimentary vitamin B6 supply during pregnancy and lactation on the
      activity of specific transaminases of lactating rats].
AB  - Eighty female Sprague-Dawley rats weighing 257 g were fed during gravidity a semi
      synthetic diet containing five vitamin-B6-treatment groups (0.6, 3, 6, 18 and 180
      mg/kg diet). The daily food intake was 14 g. During the following lactation the
      rats of each treatment group were divided into two groups containing 3 and 6 mg
      vitamin B6. At the 14th day of lactation the dams were decapitated. Parameters
      for determination of the vitamin-B6-status were activity of AST and ALT in
      plasma, erythrocytes and liver. The average activity of AST in plasma was 549
      U/l, in erythrocytes 1939 U/l and liver 106 U/g fresh matter (FM). The increasing
      vitamin-B6-supplementation during gravidity resulted in an elevated activity of
      AST between lowest and highest treatment group in plasma 56%, erythrocytes 44%,
      and in liver 43%, respectively. In response to the increasing vitamin-B6
      treatment during lactation the activity of AST in plasma increased for 19%, in
      erythrocytes for 13%, and in liver for 24%, respectively. A low vitamin-B6-supply
      (0.6 mg/kg diet) during gravidity in combination with demand-oriented supply
      during lactation (6 mg/kg diet) initiated the highest increase of activity. A
      deficient vitamin-B6-supply during lactation (3 mg/kg diet) could be compensated
      with optimal vitamin-B6-supply during gravidity. The values of ALT-activity
      showed no significant differences between the graded vitamin-B6-supplements, as a
      result of a high coenzyme saturation.

PMID- 9019918
TI  - [Letter from a reader about the work of J. Molkentin and D. Precht,
      "Determination of transoctadecenoic acids in German margarines, shortenings,
      cooking and dietary fats by Ag-TLC/GC"].

PMID- 9019917
TI  - [Hematologic changes in alimentary Pb deficiency in growing rats].
AB  - The effect of an alimentary Pb-deficiency on hematological parameters was
      examined in two growth- and one generation-experiments with female Sprague Dawley
      rats. The animals were fed a semisynthetic casein-based diet supplemented with 0
      ppb up to 800 ppb Pb as Pb-II-acetate-3-hydrate. In two experiments the blood
      parameters of the rats of G0-generation fed the diet poor in Pb were changed to a
      normocytic, normochrome pancytopenia at day 21 resp. 28 of the experiments. At
      day 28 resp. 41 the blood parameters normalized resp. the different Pb-supply in
      the diet only effected the mean corpuscular volume- and mean corpuscular
      hemoglobin-values. It was assumed that the disturbances in blood parameters at
      deficient Pb-supply are caused by temporary hemolysis.

PMID- 9019919
TI  - [The periodic action of cold and body resistance].
AB  - The analysis of phenotypic cold adaptation mechanisms and their cross-effects is
      presented in the review. The literature data and the author's laboratory
      researches became the basis of point that the cross-effects of cold adaptation
      develop owing to unspecific stress mechanisms. The negative cross-effects are
      caused by significant stress-reaction arising as a rule during continue cold
      action. On the other hand during the periodic action of moderate cold the stress
      limiting systems power increases and mainly the positive cross-effects are
      formed.

PMID- 9019920
TI  - [The creation of artificial blood and the lessons of physiology for practical
      medicine].
AB  - Nowadays the attempts to create the oxygen carrying blood substitutes
      ("artificial blood") based on the hemoglobin solution, have not met with success.
      This is accounted for by the fact that human blood hemoglobin efficiently fulfill
      the function of the gas transport in an organism only if it is included into an
      erythrocyte. The role of erythrocytes in the respiratory function of the blood is
      considered in this review. The newest methods are given of creating the
      "artificial blood" with the help of recombinant hemoglobin, the artificial
      erythrocytes and of obtaining the normal erythrocytes beyond an organism.

PMID- 9019921
TI  - [The means of integrating scientific research in the field of the physiological
      sciences under current conditions].

PMID- 9019922
TI  - [The brain dopaminergic systems: receptor heterogeneity, functional role and
      pharmacological regulation].
AB  - Recent advances in molecular neurobiology led to a new understanding on mammalian
      brain dopaminergic system which play a major role in the regulation of motor,
      cognitive, emotional, neuroendocrine function as well as in the pathogenesis of
      several pathological conditions, including neurodegenerative diseases, affective
      disorders, schizophrenia, drug addiction etc. Functional, biochemical and
      pharmacological heterogeneity of dopamine receptors, which were divided into D1
      like (D1 and D5 subtypes) and D2-like (D2, D3 and D4) families of receptors has
      been postulated. The article reviews the recent advances including author's own
      results concerning the structure and function of main dopaminergic brain system,
      i.e. nigrostriatal and mesolimbic. The problem of autoreceptor regulation of
      dopaminergic neurotransmission, particularly, the processes of dopamine
      synthesis, release and metabolism has been specially discussed. An involvement of
      D2 and D3 dopamine autoreceptors in the control of these processes and
      differences in the mode of action of typical and atypical neuroleptics
      demonstrating various affinities to D2 and D3 dopamine receptors are analysed in
      detail. Dopamine and its metabolites have been determined on freely moving rats
      using brain microdialysis and high performance liquid chromatography. It is
      hypothesized that dopamine D3 autoreceptor is preferentially involved in the
      regulation of dopamine release while D2 one is responsible for the control of
      dopamine synthesis and metabolism in rat basal ganglia in vivo.

PMID- 9019923
TI  - [Nitric oxide and carbon monoxide--a new class of signal molecules].
AB  - Recent data concerning the physiological, biochemical and pathological aspects of
      NO and CO in the brain are reviewed. Among them: biosynthesis, regulation and
      localization of corresponding enzymes (NOS, GO-2) and also cGMP in discrete
      populations of neurons; interrelationship between glutamate, NMDA-receptors, NO
      and CO; the role of NO and CO in different physiological and pathological
      processes in the nervous system, etc. On the basis of data obtained during the
      last several years, a conception of NO and CO as a novel class of signal
      molecules operating as neuromediators and/or retrograde transsynaptic messengers
      is discussed.

PMID- 9019924
TI  - [The nonspecific mechanisms of CNS adaptation to intermittent stimuli, EEG
      spectral structure and the optimal parameters of rhythmic sensory actions].
AB  - Presented paper reviews recent literature data about the role of non-specific
      mechanisms of central nervous system adaptation and intrinsic properties of
      organism functional systems in the effects of rhythmical sensory influences.
      Among the reviewed factors which determine particular effectiveness of relatively
      weak, but rhythmically organized external signals, there are such as an increased
      sensitivity of living things to different oscillatory actions, the mechanisms of
      adaptive reactions, resonance central nervous system phenomena and an interaction
      of rhythmical sensory stimulation with organism endogenous rhythms. Special
      attention is paid to endogenous rhythms in the electrical activity of the brain,
      or to the EEG rhythms. Modern state of art in the field of spectral EEG structure
      analysis is discussed, and some new approaches to rhythmical sensory stimulation
      efficacy enhancement based on individual high resolution EEG structure features
      are delineated.

PMID- 9019925
TI  - [The interoceptive properties of the vestibular apparatus (a systems analysis of
      vestibular-oculomotor interaction)].
AB  - Modern views about physiological functions of vestibular system are submitted,
      their contradictions are picked out. The result of development of experimental
      and clinical vestibulometry till last decades at the foundation of critical
      estimation of effectiveness of different methods of vestibular receptor's
      stimulation are summed up. It is proposed to consider vestibular apparatus only
      as structural sensory element of eye's moving functional system at the foundation
      of cybernetics' principles of physiological function's regularity. It is proposed
      to estimate vestibular function as a part of the whole afferent stream in system,
      which hasn't their own way at effector neurone once which determines together
      with proprioceptive afferentation internal system's status. Methodological
      principles of further research of vestibular apparatus and vestibular function
      are determined.

PMID- 9019926
TI  - [Modern concepts of the structure and function of muscle spindles in mammals].
AB  - The review provides data on the pre- and postnatal ontogenesis of muscle
      spindles. I demonstrated the roles of various sections of the nervous system in
      the mechanism of development and differentiation of the intrafusal muscle fibres.
      It provides data on the structure, dynamic and static nuclear bag muscle and
      nuclear chain fibres, their motoric and sensory innervations. It discussed the
      functional characteristics of responses from the primary and secondary endings to
      various mechanical stimulations. The paper discusses the results describing
      potentials (local and distributing) of intrafusal fibres of all types. It also
      describes the role of fusimotor innervation in regulation of the sensory activity
      of muscle spindles.

PMID- 9019927
TI  - [The regulatory role of enzymes exo- and endosecreted by the digestive glands].
AB  - Publications and our own results of researches into the role of enzymes exo- and
      endosecreted by digestive glands, acting as regulators of their secretion and
      motor activity of gastroduodenal complex were summarized. Exosecreted to its
      cavity enzymes adapt an enzymatic spectrum of secretes to the composition and
      properties of duodenal content through M-cholinergic, peptidergic, and beta
      adrenoceptive mechanisms on the basis of reception of the complex properties:
      enzyme-substrate-product. We described the effect of enzymes on the glands
      producing them, and the influence on secretion of the other digestive glands,
      regulatory effects of peptide fragments of proteolytic enzymes, and their
      zymogenic precursors. The digestive glands enzymes endosecreted and circulated in
      blood produce a hindrancing and inducing effect on these glands, take part in
      supporting of homeostasis of organism. Mechanisms of influence of enzymes and
      their fragments on the activity of digestive glands were analysed.

PMID- 9019928
TI  - [Splenic cyst--a classical "incidental finding"].
AB  - Splenic cysts cannot be summarized in one entity but open a wide field of
      aetiopathogenetic factors. The most common types of splenic cysts in central
      Europe are of epithelial or traumatic origin. Since ultrasound is widely used,
      the incidence of splenic cysts increased to about 1%. Rarely, splenic cysts give
      specific symptoms. Giant cysts cause unspecific abdominal pain, sometimes even
      organ displacement, possibly leading to a decreased function of related organs.
      In case of rupture, splenic cysts may become life-threatening. We present a
      patient suffering a giant splenic cyst and give an overview of diagnostic and
      therapeutic aspects of splenic cysts.

PMID- 9019929
TI  - [Hospital management: quality and economy as management challenges for the
      physicians].
AB  - As a consequence of the Gesundheitsstrukturgesetz (GSG-Health Structure Act)
      hospitals are called upon to organize the processes of medical, nursing care and
      administrative services more economically, without there being any reduction in
      either the social quality or the quality of the process or result of the task of
      caring for patients. Fulfilling the task of caring for patients professionally
      entails providing medical efficiency and economy (section 109 SGB V). The
      hospital management is called upon to harmonize supposedly conflicting objectives
      such as "increasing the quality whilst reducing the costs" through intelligent
      organization and leadership concepts. The maxims up to now were: "quality costs
      money", "innovations need time and money", "a shorter stay can only be guaranteed
      with additional capacity" etc. The new management paradigm demands: "higher
      quality and patient-effective innovations (e.g. minimally invasive procedures,
      out-patient operations) can be realized in a shorter time with a tendency towards
      falling costs" and "a shorter stay is achieved with less capacity through better
      organization". To guarantee these standards the doctor in particular is required
      to be a high performer because the responsibility for medical quality cannot be
      separated from the responsibility for economical work processes to achieve this
      quality. Every senior doctor when making his decision about the type and
      intensity of diagnosis and treatment automatically also makes a decision about
      executing these processes of medical services in a way which is tailored to suit
      the needs and economical requests. This management challenge for the doctor
      presents itself in several areas: --as a manager of the care cascade --as a
      manager of the services in the regional health network --as a manager of
      standardization in the field of logistics (e.g. steering of medical products like
      heart catheters from the point of manufacturing to the point of use) --as a
      manager who knows how to mobilize the problem-solving knowledge of his employees
      through delegation-orientated leadership; the concept of the management of
      wastefulness as an organization and management approach is particularly suitable
      for hospitals.

PMID- 9019930
TI  - [Modular concept for quality in the hospital--"Heidelberg model"].
AB  - The Heidelberg University Hospital meets the standards required of medical
      services in terms of efficiency, optimizing procedures, cost-effectiveness, staff
      satisfaction, and reducing infection rates etc., by implementing the Modular
      concept for quality within hospitals that has now proven its worth in practice.
      This concept combines a number of functional modules, including the hygiene,
      nursing, environment, and casualty modules, to name just four of them, within an
      overall framework incorporating guidelines focusing on quality, strategies, and
      management policies. Relevant European quality guidelines and the principles of
      Good Laboratory Practice (GLP), and Good Manufacturing Practice (GMP) are all
      taken into account to facilitate the required inter-hospital comparison with
      regard to continuous improvement of quality. It clearly demonstrates that
      expertise within the hospital and proven practicability in terms of numbers take
      definite precedence over theoretical approaches from outside experts.

PMID- 9019931
TI  - [Cost analysis of inguinal hernia surgery in ambulatory and inpatient
      management].
AB  - In Belgium 27,426 hernia repairs were performed in 1994 but only 1,451 (5.29%)
      were done on ambulatory basis, whereas in the U.S. over 50% of the yearly 600,000
      hernia repairs are one day surgery procedures with interstate variation ranging
      from 6% to 89%. The mean treatment cost of inguinal hernia repair (doctors fees +
      hotel cost) was 53,704 BEF for inpatients vs. 30,510 BEF (general anesthesia) and
      27,501 BEF (local anesthesia) for outpatients. Rates of complication and
      recurrence were not significantly different. This difference in total costs for
      hospital admission are determined by the mean length of stay and by the
      individual forfeitairy day price according to size of the hospital. Also the use
      of routine diagnostic procedures (clinical chemistry and medical imaging) - not
      necessarily essential for treatment - is higher at hospitalization. Even with 50%
      of all hernia repairs carried out in the one day clinic, total cost savings for
      treatment will hardly exceed 20% if the mean length of stay of the remaining
      inpatients will not decrease simultaneously. Supplementary and dramatic cost
      reductions however are possible by an earlier resumption of professional
      activities. The mean advised sick leave period of 4 weeks (+/- 2) still depends
      on irrelevant parameters as tradition, patients' preferences, job characteristics
      and type of insurance. Total costs for work incapacity add up to 2.5 billion BEF
      (vs. 1.4 billion BEF for total treatment costs) and can be cut by 50.18% via a
      mean 2 weeks earlier return to work. Since open primary hernia repair under local
      anesthesia can be easily carried out on outpatients resuming unrestricted daily
      activities in less than 1 week, the laparoscopic procedure with general
      anesthesia, higher treatment cost (endoscopic material) and still debated
      advantages in convalescence time and long-term outcome is not the gold standard
      for uncomplicated inguinal hernia.

PMID- 9019932
TI  - [Autologous blood donation versus homologous blood transfusion--an analysis of
      cost effectiveness].
AB  - Cost-efficiency analysis for autologous transfusions begins with the calculation
      of the pure production costs. They amount to $35-$75 for one unit of red blood
      cell concentrate (RBC). One homologous RBC is billed with $80 in Germany.
      Following factors further increase costs of an autologous blood predeposit:
      Autologous blood frequently is transfused more generously. The expiration-rate of
      autologous blood is higher. The haemoglobin content of the second and following
      RBC is lower. The patient himself has lower haemoglobin on the day of surgery
      after an autologous blood donation. In scientific examinations it is possible to
      refer additional costs of autologous blood to a gained "quality adjusted life
      year". They amount to $40,000 to $1,800,000.

PMID- 9019933
TI  - [Endoscopic hemostasis in bleeding gastroduodenal ulcer--a contribution to the
      cost aspect].
AB  - Endoscopic injections of fibrin glue for the treatment of gastroduodenal ulcer
      hemorrhage have been increasingly used instead of sclerosing agents since 1987.
      Sclerosants have the drawback that they themselves have tissue-destroying or
      rather ulcerogenic effects. A difficult form of administration and a relatively
      high price are set against the good biological properties of the fibrin glue. In
      a randomized study comparing fibrin glue with polidocanol there was a
      statistically significant lower rebleeding rate in the fibrin group. The data of
      this study were analysed with regard to economic aspects. They showed an improved
      cost-benefit and cost-effectiveness ratio of the fibrin glue compared with
      polidocanol.

PMID- 9019934
TI  - [Prognostic factors in stage I of non-small-cell bronchial carcinoma].
AB  - About 25-40% of the patients with stage I non-small cell lung cancer are not
      curable by surgery alone. Over the past years many studies on prognostic
      parameters in patients with lung cancer have been published in order to identify
      those patients, who require an adjuvant therapy. The critical assessment of these
      reports especially of those based on a certain geno- or phenotype of the primary
      tumor demonstrates that a number of different methods have been used and that the
      results are sometimes inconsistent. Therefore, a final conclusion seems not to be
      justified at this time. Recent reports describing sensitive immunocytochemical
      assays for the detection of early disseminated tumor cells in regional lymph
      nodes or bone marrow seem to be encouraging. These assays might be useful to
      identify patients at risk and the repeated analysis of bone marrow samples could
      be applied in follow-up studies to monitor the efficiency of adjuvant systemic
      therapies against minimal residual disease. In conclusion, the analysis of a
      single prognostic parameter seems to be insufficient to identify all patients at
      risk in stage I lung cancer. Thus, the establishment of a standardized profile of
      several risk factors based on a prospective, multicenter evaluation appears to be
      mandatory.

PMID- 9019935
TI  - [Pneumoperitoneum and pneumoretroperitoneum without perforation].
AB  - Asymptomatic radiologically recognised pneumoperitoneum still remains a
      diagnostic and therapeutic dilemma, because free intraperitoneal air is not
      necessarily caused by alimentary tract perforation. We present two cases of
      nonsurgical pneumoperitoneum (caused by pneumomediastinum and pneumatosis
      intestinalis cystoides) and their typical radiologic findings. Other causes of
      pneumoperitoneum that do not necessitate laparotomy so as cited in the radiologic
      and surgical literature are discussed.

PMID- 9019937
TI  - [Forrest 1b duodenal hemorrhage in previously undiagnosed primary
      hyperparathyroidism].
AB  - We report on a female patient who was suffering from a duodenal ulcer with an
      oozing haemorrhage. It turned out to be the result of an adenoma of the
      parathyroid combined with the clinical picture of an 'osteodystrophia fibrosa
      cystica generalisata', which is rarely seen. The therapy consisted in a
      parathyroidectomy.

PMID- 9019936
TI  - [Primary therapy refractory osteomyelitis of the sternum after aortocoronary
      bypass operation--a case report].
AB  - Osteomyelitis after median sternotomy for aortocoronary bypass operation is seen
      in 0.9%-2.1% of the cases described in the literature. Aetiology as well as
      adequate therapy are still in discussion. One case of foreign body induced
      osteomyelitis (pace maker electrode) with a therapy resistant osteomyelitis is
      presented and discussed in this paper.

PMID- 9019939
TI  - Proceedings of the Vienna International Anesthesiology and Intensive Care
      Congress. Vienna, Austria, October 2-5, 1996.

PMID- 9019938
TI  - [Forgotten Dresden surgeons (II)].
AB  - With the introduction of anaesthesiology and asepsis, with the progresses of
      bacteriology and of the hospital buildings the surgery at Dresden had changed
      too. A new type of surgeons replaced the old predominantly universal and military
      surgeon. At Dresden pupils of Gunther, Zeis, Kuster, Volkmann, Thiersch,
      Friedrich and Trendelenburg worked among others. The new technical and scientific
      possibilities permitted innovations of urological surgery (Grunert), paediatric
      surgery (Rupprecht), general surgery (Leonhardi, Stelzner, Lindner, Crede) and of
      plastic surgery as well as anaesthesia (Noesske).

PMID- 9019940
TI  - [Integral treatment of renal lithiasis. Present and future].

PMID- 9019941
TI  - [Treatment of prostate benign hyperplasia (BPH) with visually controlled laser,
      assessment at 2 years, and anatomopathologic findings].
AB  - The endoscopically-guided lateral discharge laser (VLAP) has been considered an
      alternative in the management of benign prostate hyperplasia (BPH). The purpose
      of this paper is to describe the technique, results obtained in 20 treated
      patients, and pathoanatomical findings in those later treated with prostate
      transurethral resection. Four patients were carriers of an indwelling catheter,
      while IPSS/QL mean values in the other 16 patients were 23/4. Mean maximum flow
      was 7.01 mL/s. Assessment after one and two years shows a fall of mean IPSS/QL to
      5/1 and mean maximum flow to 15.2 mL/s and 21 mL/s, respectively, but the
      difference is not significant. This paper also describes the morbidity affecting
      65% patients, which is comparable to the retreatment rate (15%) obtained in other
      series published. The results are similar to those described in the literature
      although, in our view, the high rate of complications undermines this choice as
      an alternative in BPH management.

PMID- 9019942
TI  - [Prostatism in patients with chronic renal failure and in renal transplant
      recipients. Comparative study].
AB  - Though hypogonadism is part of the clinical picture of chronic renal failure, its
      etiology remains unknown. Because of the consequences it may have on the prostate
      gland, it was decided to conduct a prospective evaluation on its influence on
      prostatic signs and symptoms and glandular growth in a group of patients with
      chronic renal failure undergoing dialysis and a second group with renal
      transplantation. To this end, the presence of symptoms was assessed in 78
      subjects over 50 years of age: 22 healthy controls (group C) (28.2%), 28 in
      haemodialysis (Group HD) (35.0%) and 28 with renal transplantation (Group RT)
      (35.9%). All subjects were aged between 53 and 80 years (mean 58.29 +/- 5.45).
      Determination of degree of prostatism was done by the International Prostate
      Symptoms Score (IPSS-S and L), flowmetry, ultrasound postmictional residue,
      transrectal ultrasound with 3 prostatic diameters (cross-sectional, antero
      posterior and longitudinal), prostate weight and plasma levels of PSA,
      testosterone, FSH, LH, PRL and oestradiol. In 26 of 28 patients in the HD group
      IPSS-L, flowmetry and post-mictional residue was not assessed as they had no
      spontaneous miction. There were significant differences in IPSS between C and RT
      (p = 0.003), Qmax between C and RT (p = 0.009), post-mictional residue between C
      and RT (p = 0.045), cross-sectional diameter between C and HD (p = 0.036),
      prostate weight between C and HD (p = 0.001), and between HD and RT (p = 0.001),
      PSA between C and RT (p = 0.026), FSH between C and HD (p = 0.005), LH between HD
      and RT (p = 0.020), PRL between HD and RT (p = 0.023), Oestradiol between C and
      HD (p = 0.032). We conclude that hypogonadism is a factor which, in patients with
      chronic renal failure and renal transplantation, contributes to prevent prostate
      growth thus minimizing the symptoms of prostatism.

PMID- 9019943
TI  - [Endocrine changes and sexual dysfunction in kidney transplantation and
      hemodialysis: comparative study].
AB  - OBJECTIVE: The objective of this paper is to compare the hormonal changes and
      sexual activity between transplanted patients and patients in regular
      haemodialysis (HD). MATERIAL AND METHODS: 130 patients, 98 RT carriers and 32
      with CRF were evaluated with regard to the sexual function. The etiology of CRF
      is similar in both groups. All patients underwent hormonal determinations (FSH,
      LH, Prolactin, Testosterone, Oestradiol and PTH), complete serum testing and
      other diagnostic studies done selectively, 38 of 130 patients (14 in HD and 24
      transplants) answered a personal questionnaire on sexual activity. RESULTS:
      Oestradiol and prolactin levels are higher in the HD group compared to
      transplanted patients (p < 0.05). 70% of RT patients maintain their libido versus
      35% of those in dialysis (p < 0.01). The former group refers good erection in 55%
      cases versus 21% of dialysis patients (p < 0.01). Intercourse frequency and
      degree of overall satisfaction is higher in the RT group (N.S.). CONCLUSIONS: No
      significant differences were found in FSH, LH and testosterone levels. The
      normality of FSH levels may be a reflection of the integrity of the germinal
      line. 65% HD patients refer decreased or absent libido, to which the higher
      levels of prolactin and oestradiol found could contribute. No relationship was
      found between sexual function with the type of immunosuppression or the graft
      function.

PMID- 9019944
TI  - [Assessment of vascular factor in erectile dysfunction occurred following
      surgical intervention].
AB  - Study of 33 subjects with erectile dysfunction after undergoing pelvic surgery,
      who were stratified in two groups: 16 where surgery appears to have no relation
      with the dysfunction and 17 where surgery appears to be the cause of the
      condition. They were compared with 151 cases with arterial dysfunction. Mean age
      in the group with surgery-related dysfunction (60 +/- 9.6) is higher than in the
      group with no relation (51.6 +/- 6.7) (p < 0.05), and in both cases similar to
      the group with arterial-related impotence. Both groups have vascular risk
      factors, superposed to those who had arteriogenic dysfunction. All flow-rate
      parameters in the baseline eco-doppler, degree of erectile response after
      intracavitary injection and flow-rate parameters after ICI can be superposed to
      those found in the arterial-related impotence. This suggests the existence of a
      likely pre-existent arterial disease which becomes unstable after surgery as a
      result of the vascular and nervous lesions as well as due to psychological
      changes. We insist on the need to gather information prior to surgery, and in the
      basically vascular nature of erectile dysfunctions developed in subjects who
      undergo pelvic surgery.

PMID- 9019946
TI  - [Secondary neoplasm in patients with bladder carcinoma. A case-control study].
AB  - Presentation of a case-control study on 755 subjects with the purpose of defining
      whether the development of a neoplasia on any organ and of any histological type,
      either synchronous or metachronous, occurs more frequently in patients who
      already have vesical carcinoma (338 cases) versus other populations of similar
      epidemiological characteristics comprising subjects who do not present that
      condition (417 controls). The evaluation of the difference between both groups
      establishes a cause-effect relationship expressed in terms of an odds ratio of
      2:11 which allows to claim that presence of a second neoplasia is more frequent
      in patients with vesical carcinoma (p < 0.001). The paper also includes a
      discussion on the distribution to organs and systems. Once the cases with
      urothelial site (renal pelvis, ureter or urethra) are excluded, prostate
      adenocarcinoma is the most frequent form associated to vesical carcinoma,
      followed at a distance by renal adenocarcinoma, epidermoid carcinoma of the
      larynx and bronchopulmonary carcinoma. Cumulative incidence of secondary
      neoplasias, including tumours diagnosed synchronically is 12% at 54 months.

PMID- 9019945
TI  - [Comparative study of duplex Doppler ultrasonography and dynamic cavernosometry
      by infusion in the diagnosis of arteriogenic impotence].
AB  - The findings of duplex doppler ultrasonography (DDU) of cavernous arteries (CA)
      and of dynamic infusion cavernosometry in 61 patients who underwent both
      diagnostic procedures were examined. Our work consisted in comparing the blood
      flow velocity in the CAs during the systolic peak, as measured with DDU, with the
      gradient CA occlusion pressure/mean brachial blood pressure and in attempting to
      determine whether there was a correlation between both measurements and whether
      patients were similarly classified by both methods. The results of each
      examination separately were also compared with the response to isolated injection
      of intracavernous drugs (ICI). Of the 61 patients, 56 were eligible for the study
      as 5 patients were excluded owing to a massive venous leak. A 78.6% of the
      patients were categorized similarly by both diagnostic methods. The correlation
      coefficient between both methods for the 56 evaluable patients was R = -0.756,
      implying a statistically significant correlation between the two measurements (p
      < 0.0001). The sensitivity, specificity and predictive value of a positive test
      as regards the response to the ICI of vasoactive drugs in both diagnostic methods
      showed very similar values in our sample. We conclude that both methods--the
      Doppler Ultrasonography and the measurement of the occlusion pressure of the
      cavernous arteries--are equally valid for assessing the arterial function of the
      cavernous bodies in erection. If we consider that the erectile function of the
      penis consists in storing energy in the form of pressure and that this pressure
      is supplied by the cavernous arteries, from a physiological point of view, it is
      more consistent to measure the pressure in these arteries.

PMID- 9019947
TI  - [Relationship between peripheral hypoechoic nodules of the prostatic gland and
      prostate cancer].
AB  - OBJECTIVE: The primary objective of the study was to evaluate the incidence of
      prostate cancer in the hypoechoic nodes located in the periphery of the prostate
      gland and its relationship with findings by digital rectal examination, and blood
      PSA and PSAD levels. MATERIAL AND METHODS: Retrospective study of 166 hypoechoic
      nodes detected and biopsed between January 1994 and August 1995, associating the
      pathoanatomical results with the findings from digital rectal examination, PSA
      and PSAD levels. Statistical analysis was done by estimation of confidence
      intervals for a 95% confidence level. RESULTS: Nodal cancer was present in 54.8%
      cases. The association of suspicious rectal examination increased the probability
      of cancer by 63% (IC95 = 51%-75%). The association of suspicious rectal
      examination and PSAD > 0.15 increases by 36.7% (IC95 = 11.7%-61.1%) the
      probability of having cancer versus a suspicious digital rectal examination
      alone. When no suspicious rectal examination was considered, the difference in
      the proportions observed for PSA > 10 versus PSA levels > 4 and < or = 10 ng/mL
      is 13.7% (IC95 = -2.1%-29.4%) and, for PSAD > 0.15 versus PSAD < or = 0.15 was
      11.6% (IC96 = 3.8%-27.1%). CONCLUSIONS: Presence of a suspicious rectal
      examination and PSAD > 0.15 increased significantly the probability of prostate
      cancer being present in the hypoechoic node. When digital examination is not
      suspicious, neither the PSA or the PSAD levels influence significantly in the
      appearance of cancer.

PMID- 9019948
TI  - [Endourologic treatment of ureteral ruptures in closed abdominal trauma].
AB  - The traumatic fracture of the ureter is a very uncommon entity, which accounts
      for 1-5% of all urological traumatism. In most cases it is secondary to
      penetrating lesions, endoscopic or open surgery iatrogeny, its occurrence as
      secondary to closed traumatism being very rare. The paper presents four patients
      with partial ureteral fractures caused by closed traumatism. Management was in
      all cases conservative with endourological methods, using backward ureteral
      intubation, and no case required the use of other types of complementary surgical
      approaches; functional recovery of urinary tract was complete in all four
      patients.

PMID- 9019949
TI  - [Cystic lymphangioma of the adrenal gland in adults. Review of the literature and
      report of a new case].
AB  - Presentation of one case of cystic lymphangioma of the suprarenal gland in a 34
      year-old female patient with a background of lower urinary tract infections,
      presenting with continuous and aggravating pain in left lumbar area and with no
      other associated symptomatology, diagnosed with ultrasound, IVU and CAT. A review
      of the literature is made. The present study pretends to give an overall view of
      a rare and benign disease, commenting upon the difficulties found in its
      diagnosis and the different therapeutical options.

PMID- 9019950
TI  - [Malignant fibrohistiocytoma of the renal capsule. Report of a case and review of
      the literature].
AB  - Presentation of one case of malignant fibrohistiocytoma derived from the renal
      capsule. While conducting a bibliographic review the low incidence of this
      tumoration of renal origin was noted. The difficulties in differentiating this
      entity from a secondary renal invasion by a malignant fibrohistiocytoma derived
      from other retroperitoneal structures is commented. Brief review of current
      diagnosis and therapeutical management for this tumoral entity.

PMID- 9019951
TI  - [Pyonephrosis caused by torulosis glabrata].
AB  - Fungal urinary infections are becoming increasingly frequent as a result of
      widespread use of broad spectrum antibiotics, an increased number of
      immunocompromised patients and the greater longevity of chronic patients. Urinary
      tract infections by Toruplosis glabrata only come second in frequency after those
      caused by Candida albicans, accounting for 5 to 25% of all infections caused by
      fungi. The paper presents one case of pyonephrosis by Toruplosis glabrata in a
      female patient treated with fluconazole who later underwent nephrectomy. A
      description is made of the clinical picture, diagnosis and treatment of these
      infections.

PMID- 9019952
TI  - [Complicated spermatocele as a cause of scrotal mass with solid appearance.
      Ultrasonographic findings].
AB  - We report an atypical case of spermatocele in which sonographic findings
      demonstrated an intraescrotal mass fixed to the testicle, apparently solid and
      with important vascularity, being these findings suspicious of malignant tumor.
      We recommend to include complicated spermatocele in the differential diagnosis of
      ecographically solid masses.

PMID- 9019953
TI  - [Intratumor and retroperitoneal massive hemorrhage caused by retroperitoneal
      liposarcoma].
AB  - Case report of a giant retroperitoneal liposarcoma which presented with a picture
      of acute abdomen resulting from a massive tumoral haemorrhage. Diagnosis was
      achieved by ECO and CT, and was confirmed by Pathological Anatomy. Treatment was
      surgical, performing tumour removal plus polar nephrectomy of the affected side.
      The patient evolution was favourable. The standard methods of diagnosis and
      prognostic factors are commented.

PMID- 9019954
TI  - [Heart block caused by hyperkalemia as a complication of ureteroileostomy].
AB  - Report case of a patient who, after an ureteroileostomy, developed complete
      atrioventricular block secondary to severe hyperkaliemia, a condition for which
      no references have been found in the literature. Special mention is made of the
      mechanisms which trigger the electrolytic changes in these by-pass techniques.

PMID- 9019955
TI  - [Wallstent prosthesis of unusual location caused by recurrent urethral stenosis
      following repeated urethroplasty].
AB  - Presentation of one case of relapsed urethral stenosis in a penoscrotal location
      where after several failed therapeutical approaches, the final decision was to
      place a Wallstent endoluminal prothesis. The patient underwent several endoscopic
      internal urethrotomies and urethroplasty in two occasions, developing
      complications: urethral calculi, hair follicles requiring cauterization, repeat
      infections and relapse urethral stenosis, which finally lead to the decision of
      fixing a intraluminal stent even if in an unusual location (penoscrotal). The
      result, 40 months after implantation, is both subjectively and objectively
      better, with a good mictional calibre and satisfactory erection which allows the
      patient to have sexual intercourse. The Wallstent prothesis can be the ultimate
      alternative in those cases of "ill-treated" urethra where other techniques fail.

PMID- 9019956
TI  - [Current treatment of ureteral lithiasis].

PMID- 9019957
TI  - [Re: Prediction of continence in patients with neurogenic bladder who will be
      undergoing bladder augmentation].

PMID- 9019958
TI  - Decision of vaccination strategy in relation to increased trade of animals and
      animal products. Proceedings from the 9th Internordic Symposium of the Nordic
      Committee of Veterinary Scientific Cooperation. Copenhagen, 1-2 December 1995.

PMID- 9019959
TI  - [Penicillin resistant pneumococcus. A serious problem of public health].

PMID- 9019960
TI  - [Should fluoride supplementation be administered to infants?].

PMID- 9019961
TI  - [Mononucleosis syndromes with serology doubly positive to Epstein-Barr virus and
      cytomegalovirus].
AB  - OBJECTIVE: The objective of this study is to present cases of infectious
      mononucleosis syndromes (i.m.) with dual rises in antibodies towards Epstein-Barr
      virus (EBV) and cytomegalovirus (CMV). PATIENTS AND METHODS: A prospective study
      of 49 children that fulfilled Sumaya's clinical criteria was carried out.
      RESULTS: Fifteen cases of i.m. were serologically positive for EBV, 12 for CMV, 2
      for toxoplasma and 10 were serologically negative. The other ten had dual
      antibody rises to EBV and CMV. The symptoms were similar in the different groups.
      Significant differences were found only for the age at the time of presentation
      where below 4 years of age i.m. is rarely due to EBV (p < 0.01). Analytically,
      only elevated serum transaminase concentrations suggested the etiology of EBV (p
      < 0.05). Although i.m. with dual antibody rises towards EBV and CMV are more
      similar to cases due to EBV, they present characteristics from both viruses.
      CONCLUSIONS: 1. There are i.m. with dual antibody rises to EBV and CMV 2. The
      meaning still remains unknown, but there are two hypotheses: coinfection or
      "endogenous reinfection". 3. Cases of EBV-i.m. and CMV-i.m. are clinically
      similar, except at the age of presentation and the rising of serum transaminase
      concentrations.

PMID- 9019962
TI  - [Sexual child abuse. Our one-year experience].
AB  - OBJECTIVE: We have analyzed our population in regards to child sexual abuse
      during 1994 and propose a diagnostic classification of our findings. PATIENTS AND
      METHODS: We reviewed retrospectively 18 cases of abuse, collection in each case
      the following data: age, sex, reason for the consultation, family situation,
      perpetrator, positive clinical history or not, physical findings, psychological
      disorders and complementary examinations. We established 4 classification levels:
      normal, compatible with abuse, suspicious and sexual contact or certain
      penetration. RESULTS: The number of children attended was 18. Thirteen (72%) were
      female. The youngest was 1 month old and the oldest 14.5 years. The clinical
      history was positive in 6 cases. The physical findings allowed a certain
      diagnostic in 3 cases. Presence of semen was demonstrated in 1 case and 1
      positive culture for gonococci was obtained. The final diagnosis was normal in 6
      cases, compatible with abuse in 4, suspicious in 3 and certain sexual contact or
      penetration in 5. CONCLUSIONS: The diagnosis of sexual abuse is very difficult.
      The clinical history is still necessary due to the fact that physical findings
      and complementary tests tend to not be conclusive. We propose that once the
      information has been evaluated the conclusion be classified into 4 groups:
      normal, compatible with abuse, suspicious and certain sexual contact or
      penetration.

PMID- 9019963
TI  - [Assessment of 200 critically ill transferred children at a pediatric intensive
      care unit].
AB  - BACKGROUND: Pediatric intensive care units have developed as treatment areas with
      a concentration of specialized equipment and personnel. Critically ill children
      often need to be moved to and from these critical care areas for diagnostic or
      therapeutic procedures. Such transport may pose additional risk to the critically
      ill patient. PATIENTS AND METHODS: In order to assess the problems encountered in
      our transport process, a prospective study was performed. A questionnaire was
      undertaken to evaluate the transport of critically ill children hospitalized in
      the Pediatric Intensive Care Unit of the Hospital Universitario Puerta del Mar
      from Cadiz over an eleven month period. RESULTS: Two hundred children transported
      were evaluated. Forty-seven (23.5%) were interhospital transported patients and
      one hundred fifty-three (76.5%) were intrahospital transported patients. The most
      common type of intrahospital transport involves transfers between the operating
      room and the intensive care unit (73 patients, 36.5%). Deterioration in
      respiratory, cardiovascular and other physiological systems was registered in
      twenty-two patients (11%). One hundred four equipment-related mishaps were noted
      in eighty-six patients (43%) during the transport process. Dislodgement of
      intravenous catheters, loss of oxygen supply, endotracheal tube problems and
      equipment malfunction were the most common mishaps noted. CONCLUSIONS: Our
      results would suggest that more training regarding the transport of the
      critically ill child are needed in our area.

PMID- 9019964
TI  - [Does the degree of metabolic control of diabetes mellitus affect the blood
      concentration of endothelins?].
AB  - BACKGROUND: Endothelins are a family of peptides with a potent constriction
      action that can play a role in the etiology of vascular diabetic complications.
      PATIENTS AND METHODS: We studied 26 prepubertal patients diagnosed with type I
      diabetes mellitus and treated by both insulin and dietetic regime. They were
      analyzed according to their age. A morning blood sample was obtained after 12
      hours of overnight fasting for endothelin determination (RIA from Nichols
      Institute) and HbA1c (Biorad). Patients were classified into two groups: 1) good
      control, with HbA1c values < 8% and 2) poor control with HbA1c levels > 8%. The
      control groups was comprised of endocrinologically normal children that consulted
      the pediatrician for suspected constitutional delay of growth. Statistical
      analysis was made by means of nonparametric methods and with the Spearman
      coefficient. RESULTS: In the control group, the plasma concentration of
      endothelin were 4.01 +/- 1.1 pg/ml (x +/- SD). In diabetics with good control,
      values were 3.15 +/- 0.62 pg/ml and 3.91 +/- 1.25 in diabetics with poor control.
      No statistical differences were noted among these groups. CONCLUSIONS: We deduce
      that plasmatic levels of endothelin does not seem to be affected by the metabolic
      control in patients with type I diabetes mellitus without complications.

PMID- 9019965
TI  - [Epidemiology of epilepsy in pediatric age: types of epileptic crises and
      epileptic syndromes].
AB  - OBJECTIVES: 1. To study the epidemiological characteristics and types of
      epileptic seizures in infancy. 2. To evaluate our experience with the ILAE
      classification of epilepsies and epileptic syndromes and to study the relative
      frequency of the different epileptic syndromes. PATIENTS AND METHODS: All
      patients under 14 years of age that were evaluated for one or more unprovoked
      seizures in a primary care hospital between January 1, 1988 and June 1, 1994 were
      prospectively included in the study. In the 151 patients that met these criteria,
      we studied the epidemiological characteristics, predominantly the type of seizure
      and the classification as to type of epileptic syndrome. RESULTS: 1. ETIOLOGY: Of
      all of the seizures, 18% were considered symptomatic with a predominance in the
      first three years of life (34%), 28% were idiopathic with the predominance of
      cases occurring over three years of age (34%) and 54% cryptogenic, with an even
      distribution in all age groups. 2. Epileptic seizure type: Patients under 3 years
      old had 17% generalized epilepsies, 20% localization-related, 31% undetermined
      and 31% isolated seizures. In the 4-9 year olds, had 12%, 51%, 4%, and 32%,
      respectively. Between 4-14 years of age, benign rolandic epilepsy accounted for
      17% of the epilepsies. Sixty-two percent of the patients remained classified in
      nonspecific categories (26% isolated seizures, 16% undetermined and 20%
      cryptogenic localization-related). CONCLUSIONS: The study of unprovoked seizures
      in children shows marked differences in the different age groups in respect to
      epileptic seizure type, etiology and epileptic syndrome classification. The
      application of the ILAE classification system leaves the majority of patients in
      non-specific categories.

PMID- 9019966
TI  - [Usefulness of oxygen saturation in the assessment of children with moderated
      laryngitis].
AB  - OBJECTIVE: The aim of this study was to determine the usefulness of oxygen
      saturation (SaO2) in the assessment of a child with moderate laryngitis (croup).
      PATIENTS AND METHODS: A prospective study was carried out on 54 cases of moderate
      laryngitis (score of 2 to 6 of a possible 16) attended at our emergency
      department. Clinical score, heart rate, respiratory rate and SaO2 were recorded
      upon arrival. We analyzed the relationship between SaO2 and the requirement of
      nebulized epinephrine, parenteral dexamethasone and admission to the hospital.
      RESULTS: Patients who received epinephrine showed SaO2 values lower than those
      who did not (96.8 +/- 1.9 vs 97.9 +/- 1.7), although this was not a significant
      difference (p = 0.11). Similar findings were seen when the requirement of
      parenteral dexamethasone was analyzed (96.7 +/- 1.9 vs 97.3 +/- 1.8, p = 0.28).
      Children admitted to the hospital showed SaO2 values significantly lower than
      those discharged (96.5 +/- 1.9 vs 97.6 +/- 1.7, p = 0.03). No differences were
      seen when heart rate or respiratory rate were analyzed. CONCLUSIONS: We conclude
      that the measurement of is SaO2 useful in initial assessment of a child with
      acute laryngitis, essentially in order to better identify those patients who
      require admission to the hospital. It appears reasonable to include it in the
      initial assessment score.

PMID- 9019967
TI  - [Why are children hospitalized in Spain?].
AB  - OBJECTIVE: Hospital services represent a significant amount of the overall health
      care devoted to the pediatric population. This work describes regional
      differences in Spanish pediatric hospital admissions. PATIENTS AND METHODS:
      National, regional, age-specific and diagnostic-specific discharge rates were
      obtained from the 1987 Hospital Morbidity Survey. To assess regional variations,
      weighted coefficient of variations (WCV) were obtained. RESULTS: The overall
      national discharge rate was 60.45 discharges per 1000 children less than 15 years
      of age. The weighted coefficient of variation obtained for the sex and age
      adjusted discharge rates of the 10 more frequent diagnoses was highest for
      phimosis (56.13) and lowest for appendicitis (19.44). CONCLUSIONS: Differences in
      supply and professional practice style have been recognized as causes for the
      variations in hospital utilization. Hospitalization of patients represents costs
      and risks. They are justified when scientific evidence shows that their suggested
      benefits overcome their inconveniences. The existence of this difference leads to
      suspect that non-clinical factors could be decisive in medical decisions.

PMID- 9019968
TI  - [Anophthalmia/micro-ophthalmia in syndromes: epidemiology study of newborns in
      Spain].
AB  - OBJECTIVE: The objective of this study was to perform an epidemiological analysis
      of the frequency of anophthalmia/microphthalmia (A/M) in syndromes identified in
      newborn infants in Spain. PATIENTS AND METHODS: Data of the Spanish Collaborative
      Study of Congenital Malformations during the period of 1976-1994, corresponding
      to more than 1,200,000 births, was analyzed. Among these, 86 newborn infants with
      A/M presented some of the recognized syndromes. RESULTS: There is a wide
      etiological heterogeneity among the syndromes with this ocular defect, with
      chromosomal syndromes being the most frequent (67.9% of total syndromes with
      A/M), followed by monogenic syndromes (19.1%), environmental (9.5%) and those of
      unknown etiology (3.6%). CONCLUSIONS: Some guidelines when a baby is born with
      A/M are derived from this study. First, given the tendency of the defect to
      present together with other anomalies, it is advisable to perform a detailed
      study to rule out or to confirm the existence of other defects. Adequate samples
      should be taken (even in stillborn infants) for cytogenetic study. Examine
      carefully the prenatal history, looking for chronic diseases, infectious
      processes or exposure to teratogens. Depending on the baby's survival, follow-up
      of the psychomotor development should be made. All of these aspects are always
      important in malformed babies, but especially in infants with A/M given the
      tendency of the defect to present in syndromes as the etiologic diagnosis
      determines the counselling regarding the risk of recurrence, detection of
      carriers in some cases and possible prenatal diagnosis.

PMID- 9019969
TI  - [Syndromes with neural tube defects: epidemiologic analysis in Spain].
AB  - OBJECTIVE: We present, from an epidemiological perspective, the analysis of
      syndromes which present neural tube defects (NTD). Although there are many
      epidemiological studies on NTD all over the world, most of them are on isolated
      NTD; that is, when the infant only has NTD as the only anomaly. PATIENTS AND
      METHODS: The methodology is based on the review of hospital records of infants
      with congenital anomalies. This permitted the analysis of the prevalence.
      RESULTS: The results show that the frequency of syndromes with NTD is 27.5 time
      higher among stillborn infants than among liveborn infants. Nevertheless, there
      are not many syndromes in which the NTD are present more or less frequently. In
      fact, only 1.93% of the total cases with syndromes presented NTD, with the
      majority (43.4%) with genetic etiology. We also analyze the specific types of
      syndromes with NTD.

PMID- 9019970
TI  - [Quantification of fecal excretion of trace elements in newborns as expression of
      fetal intestinal secretion].
AB  - OBJECTIVE: Trace elements have acquired major importance in the knowledge
      concerning corporal composition and in the comprehension of their metabolic
      participation in organic processes. The objective of this study was to know the
      concentration of trace elements in biological material (serum, meconium and
      feces) from preterm and fullterm infants during the neonatal period. PATIENTS AND
      METHODS: Concentrations of Al, Ca, Cr Cu, Fe, Mg, Mn, Mo, P, Pb and Zn were
      determined simultaneously in stools and serum by induction coupled argon plasma
      atomic-emission spectrometry (ICP) of 12 preterm and 38 fullterm infants. Stools
      were collected for the 1st (meconium), 10th and 20th day and serum on the 10th
      day. RESULTS: Compared to serum from preterm infants, fullterm infants had an
      elevated (p < 0.05) value of potentially toxic trace elements (Al and Pb).
      Compared meconium from fullterm infants, preterm infants had an elevated
      excretion of Cu (p < 0.001) and Fe (p < 0.01). Compared to stools from the 10 and
      20th day from preterm infants, fullterm infants had an elevated excretion of Fe
      (p < 0.05). Stool excretion of all of the trace elements increases throughout the
      days during the neonatal period, whereas Mn decreases. CONCLUSIONS: The mineral
      content of meconium and stools in newborns rarely has been described and ICP is
      an interesting method of assessment of trace elements in these biological samples
      during the neonatal period.

PMID- 9019971
TI  - [Leigh syndrome caused by cytochrome-C oxidase deficiency: a clinical case].

PMID- 9019972
TI  - [Superior mesenteric artery syndrome: an infrequent cause of duodenal obstruction
      in childhood].

PMID- 9019973
TI  - [Cutaneous larva migrans].

PMID- 9019974
TI  - [Intracranial dissemination of intramedullary malignant glioma. Report of a
      pediatric case].

PMID- 9019975
TI  - [Multiple intracranial tuberculomas].

PMID- 9019976
TI  - [Miller-Dieker syndrome and endocrine changes in twins].

PMID- 9019977
TI  - [Simple epididymal cysts in puberty].

PMID- 9019978
TI  - [Leigh disease in an infant with deficiency of complex I of the mitochondrial
      respiratory chain].

PMID- 9019979
TI  - [Fetal alcoholic syndrome associated with trisomy X].

PMID- 9019980
TI  - [Adolescent with acute sciatica and fever].

PMID- 9019981
TI  - [Introduction to molecular biology and application to pediatrics (1): basic
      concepts].

PMID- 9019983
TI  - [Medical treatment of multinodular goiter].
AB  - Thyroid nodules are among the most common clinical problems in endocrinology.
      Among several factors responsible for the development of goiter, circulating TSH
      plays a major role because of its direct growth-promoting effects on the thyroid
      cells; moreover TSH may enhance the effects of other local growth factors which
      act in a paracrine mode in the thyroid gland. In addition, autoimmune thyroiditis
      can clinically appear as thyroid nodules frequently with the functional aspect of
      a subclinical hypothyroidism. For these reasons a therapeutical approach based on
      the thyroxine suppression of TSH secretion has become largely used by 1970s and
      is correctly employed in 75% of the patients with thyroid nodules whose biopsies
      result benign.

PMID- 9019982
TI  - [Multinodular goiter. Epidemiology and prevention].
AB  - Nodular goiter is the natural evolution of nontoxic goiter, that may be endemic,
      sporadic or familiar. Iodine deficiency is the cause of endemic goiter, while
      genetical defects, impairing the thyroid hormone biosynthetic efficiency or
      altering the number and/or activity of growth factor receptors, play the major
      role in the pathogenesis of sporadic and familiar nontoxic goiter. The prevalence
      of nodular goiter is directly related to the degree of iodine deficiency that is
      still present in several areas of the world. In iodine deficient areas such as
      some Italian regions, nodular goiter is present in 25-33% of the population, its
      frequency increasing with age. In iodine sufficient areas the prevalence of
      nodular goiter is comprised between 0.4 and 7.2% high in iodine deficient areas
      and about 4% in iodine sufficient countries, its frequency increasing with the
      age. Dysphagia, dyspnea and coarsening of the voice may occur for esophagous,
      tracheal or laryngeal nerve compression, respectively. Iodine deficiency has
      little if any effect on the frequency of thyroid carcinoma, while, with regard to
      the histological pattern, it leads to an increased ratio papillary/follicular.
      Thyroid function is normal in uncomplicated nontoxic goiter. However, the
      evolution of nodular goiter is toward the functional autonomy of nodules that may
      result in thyrotoxicosis. Hypothyroidism is rare and is usually the result of
      thyroid autoimmunity. All the cases due to iodine deficiency can be prevented by
      an adequate iodine prophylaxis that can be accomplished in industrialized
      countries by the use of sale enriched in iodine.

PMID- 9019984
TI  - [Goiter surgery].
AB  - In the course of 26 years at the 3o Surgical Department of University of Rome "La
      Sapienza" 6,009 patients with thyroid diseases were operated on since 1970
      through September 1995. There were 3,473 goiters and in 373 of them a carcinoma
      was found. The great majority of patients with goiter was treated by subtotal
      thyroidectomy. Total thyroidectomy was performed in the 373 patients with thyroid
      cancer and in diffuse nodular goiters interesting the whole gland. No
      perioperative mortality is reported. No recurrent laryngeal nerve iatrogenic
      palsy was observed. The incidence of temporary hypoparthyroidism had a percentage
      of 10% after total thyroidectomy and of 0.1% after unilateral lobectomy plus
      istmectomy or bilateral subtotal resections.

PMID- 9019985
TI  - [Surgical treatment of multinodular goiter].
AB  - A homogeneous series of 361 patients operated on for multinodular goitre was
      analyzed. Minimum and mean follow-up were 10 and 18.6 years, respectively. In
      most cases a subtotal or near total thyroidectomy was performed, while total
      thyroidectomy was reserved for patients with cancer. The goal of the study was to
      verify the long term outcome of this therapeutic strategy in terms of
      complications, disease recurrence, need of complementary therapies (TSH
      suppressive or substitutive) and reinterventions. Global recurrences were 14.7%,
      and 4.9% of these needed a second operation for indications similar to those of
      the first operation. Long term complications were vocal cord palsy 1.1% and
      permanent hypoparothyroidism 0.3%, while the global complications of
      reinterventions were 3% (n.s.). Nearly half of the patients had not followed any
      functional or instrumental check-up for at least 5 years nor undergone any
      hormonal therapy. Among the patients who had a TSH-suppressive therapy, the
      recurrence rate was not significantly different compared to the group that had no
      treatment. On the basis of these data, it seems that subtotal thyroidectomy is
      adequate intervention for multinodular goitre, as long as the number of clinical
      recurrences is not significantly high. On the contrary, it might be expected that
      total interventions, performed in non specialized centers, would introduce a
      higher rate of complications. The need for TSH-suppressive therapy to reduce
      recurrences was not proven.

PMID- 9019986
TI  - [Postoperative organotherapy for multinodular goiter].
AB  - Post-operative therapy with L-Tiroxine can have a suppressive or substitutional
      aim. After a total thyroidectomy the patients need a substitutional therapy,
      while after subtotal thyroidectomy the aim of the therapy is to suppress the TSH
      secretion. In the second case we want either to avoid the recurrence, either to
      give the hormones that residual gland cannot produce. The drug of choice is L
      Tiroxine for both suppressive o substitutional therapy: There is a difference in
      dosage, that must be greater in first case. While there are some doubts in the
      literature on the success of the suppressive therapy, we believe that there is
      enough evidence of his utility.

PMID- 9019987
TI  - [Cancer in multinodular goiter].
AB  - Multinodular goitre is a very common, and commonly benign, thyroid disorder;
      however variable and sometimes surprisingly high occurrence of malignancy has
      been reported in surgical series. In this connection we retrospectively analyzed
      a large consecutive series of 539 thyroidectomies performed for M.N.G. over a
      short period of time of 3 years: there were 455 female and 84 male patients, of
      whom 522 over and 17 under 21 years of age. It was found an overall incidence of
      carcinoma of 7.5% (90.2% of papillary type), with prevalence in female (8.3%) vs
      male sex (3.6%) and in patients under (11.7%) vs over (7.5%) the age of 21 years;
      differences for sex and age were not significant. We remark that present revision
      left out of consideration other known factors predisposing to cancer, and
      included occult papillary carcinomas that are a frequent autoptic finding and do
      not affect life expectancy. Surgical selection, in addition to these
      circumstances, concurred to distort, making higher than true, the incidence of
      cancer in M.N.G. We conclude that M.N.G. cannot be considered as a condition
      predisposing to cancer but it may harbour a cancer; since that selective surgical
      approach is recommenced. Selection criteria for surgery and treatment are
      mentioned.

PMID- 9019988
TI  - [Recurrent goiter: analysis of 134 reinterventions].
AB  - Reoperative surgery for thyroid disease still plays a predominant role in the
      treatment of goiter recurrences. At the moment, neither useful biological nor
      clinical indicators exist to prevent such recurrences. The effectiveness of TSH
      suppressive therapy is still debatable and some authors have proposed total
      thyroidectomy for this benign disease in order to eliminate the risk of relapse.
      We analyzed 134 patients who underwent reintervention for recurrence of goitre in
      order to: 1) study possible clinical or epidemiological characteristics that
      could influence recurrence, 2) to verify the indications to reoperation, and 3)
      to evaluate the incidence of complications. For the study of complications, we
      adopted as a control group a series of 361 patients operated on by the same
      medical staff and undergoing subtotal thyroidectomy for multinodular goitre, with
      a minimal follow-up of 10 years. The surgical technique is described and several
      peculiarities are discussed. In the group of patients who had reoperation two
      cases (1.5%) of laryngeal palsy and two cases (1.5%) of hypoparathyroidism were
      recorded and this was not significantly different from the control group. A
      positive correlation was found between recurrence and young age at the time of
      first surgery (p < 0.006), female sex (p = 0.045) and esthetic results (p =
      0.013). No further clinical recurrence was found in 101 patients after a mean
      follow-up of 122 months, while in 16 cases the echography revealed nodules in the
      residual parenchyma. In our opinion total thyroidectomy is not justified as a
      first standard procedure for this benign disease caused by the activity of
      various not yet well understood, growth factors.

PMID- 9019990
TI  - [Tools for assessing the quality of care in health facilities. Experience in
      Ferrara].
AB  - Studies of health care quality are based on the evaluation of the way of how
      knowledges and available resources interact in order to guide individual
      behaviour as well as organisational planning. We have tested a sample of
      patient's impressions, using an anonymous questionnaire. During a period of 12
      months 1039 patients have been questions. The result of our study demonstrates
      the necessity of a closer cooperation between general practitioner and in
      hospital physician even in order to guarantee communication and promote trusting
      between hospital and patients.

PMID- 9019989
TI  - [Surgical treatment of cervico-mediastinal goiter].
AB  - Over the last decades definitions and classifications of cervico-mediastinal
      goiters have been proposed. According to the definition of Valdoni and Tonelli,
      from 1968 to 1991 237 patients were operated on for cervico-mediastinal goiter.
      There were 168 simple forms (141 anterior and 27 posterior) and 69 complex forms
      according to Borrelly's classification. We analyse and discuss the clinical
      presentation, the diagnostic procedures and the surgical technique in relation to
      post-operative complications and long term results. The mean duration of symptoms
      before surgery in patients with cervico-mediastinal goiter was longer than in
      subjects with cervical goiters. All but 8 operations were performed through a
      cervical incision. Two patients, both with advanced tumor, died postoperatively.
      Post-operative complications were: hemorrhage 0.8%, dysphonia 4.6% and transient
      hypoparathyroidism 2.9%. A clinical follow-up was available for 194 patients.
      Permanent dyspnea was observed in 1.0%, dysphonia in 4.6% and transient
      hypoparathyroidism in 2.9%. Tracheotomy was necessary in 5 cases. Complications
      were more frequent after total thyroidectomy than after partial resection (p <
      0.05), after surgery for malignancy than for benign disease (p < 0.05) and in
      complex than in simple forms (p < 0.05). Almost all cervico-mediastinal goiters
      can be treated by a cervical incision. Sternotomy, when required, does not
      influence mobility and mortality. The lacking of an alternative treatment, the
      relatively high incidence of malignancy and the risk of acute airway obstruction
      should induce the early removal of all substernal goiters.

PMID- 9019991
TI  - [Early gastric cancer: our experience].
AB  - The early gastric cancer (EGC) is a very interesting pathology as it represents
      the first phase of gastric cancer, curable in most cases. The aim of the present
      study is to evaluate the outcome of surgical treatment of EGC in 19 consecutive
      patients. The studied patients were followed up for 5 years, during which they
      underwent a gastroscopy, a hepatic echography and a TC at one year intervals in
      case of echographic suspicion. Ten patients with limited involvement of the
      antrum underwent a gastric resection with Billroth II's reconstruction; five
      patients with circumscribed involvement of the gastric body underwent a subtotal
      resection; four patients (one with a multifocal involvement of the gastric body
      and three with multifocal involvement of the fundus) underwent a total
      gastrectomy with Roux's reconstruction. All patients underwent a limited
      lymphadenectomy of the perigastric lymph nodes. By evaluating and comparing the
      results of the present study with previous data on EGC, we propose gastric
      resection, subtotal gastrectomy and total gastrectomy, according to the location
      of neoplasm, with limited lymphadenectomy of perigastric lymph nodes.

PMID- 9019992
TI  - [Preoperative blood storage and intraoperative blood recovery in elective
      treatment of abdominal aorta aneurysm].
AB  - We evaluated the efficiency and costs-effectiveness of blood predonation and
      intraoperative salvage in elective abdominal aortic aneurysm surgery. Between
      January 1992 and January 1994, 66 patients (59 male and 7 female, aged 69.9 +/-
      0.8 years) who underwent elective surgical repair of an AAA were selected for the
      study. Thirty-six (54.5%) patients (Group 1) intra- and/or postoperatively
      received homologous blood whereas 30 (45.5%) patients (Group 2) received
      autologous blood predonation and intraoperative blood aspiration and reinfusion.
      The two groups were similar for demographic data, aneurysmal diameter and
      associated diseases and/or risk factors (p = NS). Operative mortality was
      comparable between the two groups (p = NS). The mean intraoperative blood loss
      was 803.4 +/- 104.5 ml in group 1 and 812.8 +/- 44.8 ml in group 2 (p = NS).
      Group 2 patients received intra- or postoperatively a mean of 0.8 +/- 0.2 units
      of homologous blood (p < 0.001). Aneurysmal diameter did not influence the
      transfusion requirement between the two groups (p = NS). The cost per unit of
      homologous banked blood was significantly higher (p < 0.01). Cumulative costs of
      the procedures did not show statistical differences between the two groups (p =
      NS). Aortic surgery is the ideal target for predonation and intraoperative blood
      salvage.

PMID- 9019993
TI  - [Thoracoscopic bilateral sympathectomy in Raynaud's syndrome. Anesthesiology
      problems].
AB  - The objective of this paper was to examine the major anaesthetic problems during
      transthoracic endoscopic sympathectomy without artificial pneumothorax and to
      present our experience of 16 cases suffering from Raynaud's disease. For the
      perioperative management we used a double lumen endo-bronchial tube and balanced
      anaesthesia (intravenous agents plus isoflurane). Arterial pressure, heart rate,
      ECG, end-tidal carbon dioxide concentration, SatO2, blood gases and peak
      inspiratory pressures were monitored. The results showed that no significant
      changes in these parameters occurred during surgery. Since hypoxaemia is the main
      problem of the thoracoscopic sympathectomy the A.A. emphasize the necessity to
      ensure a correct ventilation as well as a haemodynamic stability throughout the
      procedure. The combination of balanced anaesthesia and double lumen endobronchial
      intubation seems an advisable method when no artificial pnx is instituted. A
      close monitoring of the circulatory and respiratory systems is imperative.

PMID- 9019994
TI  - [Arteriomegaly in the aorto-iliac-femoral area with or without associated
      aneurysm].
AB  - The authors present a group of 199 patients with arteriomegaly, an affection
      characterized by elongated and distended blood vessels of the arterial system,
      with or without accompanying aneurysms. Our study on this group of patients,
      drawn from a large arteriographic series of peripheral abdominal and lower limb
      arterial disorders, focuses on a comparison between atherosclerotic arteriopathy
      and arteriomegaly. Small tissue blocks were taken from the arterial wall of
      patients operated on for megadolichoarteries. Electron microscopic examination of
      such specimens revealed a specific alteration of the elastic component of the
      vessel wall. The authors believe that surgical treatment of this condition is
      indicated in order to prevent thromboembolic complications or aneurysmal rupture.

PMID- 9019995
TI  - [Sutures without sutures in digestive surgery. Experimental study of the rat
      intestine].
AB  - The aim of the experimental study was to evaluate the possibility of performing
      an end-to-end anastomosis by using fibrin adhesive as the only means of suture.
      To this end, 24 Wistar rats were used, of which 16 underwent ilear resection and
      8 underwent colotomy, and they were divided respectively into two groups. On the
      rats of the first group the anastomosis was performed by using only fibrin
      adhesive; on the rats of the second group operated the anastomosis was performed
      by using fibrin adhesive in association with non adsorbable suture material,
      while on those operated of colectomy the anastomosis was performed by fibrin
      adhesive and adsorbable suture material. The anatomo-phatological studies on the
      anastomosis have shown a similar healing process in the cases treated only with
      fibrin adhesive and by using absorbable material and has demonstrated the trange
      material from the suture, which are a possible causes of complication.

PMID- 9019997
TI  - Peroxisomes: Biology and Role in Toxicology and Disease. Proceedings from an
      international symposium. Aspen, Colorado, June 28-July 2, 1995.

PMID- 9019996
TI  - [Ultra-low laparoscopic rectal resection and colo-anal anastomosis. Experimental
      study on swine].
AB  - Nowadays oncologic surgery is defining new criteria in the treatment of rectal
      cancer: preservation of sfincterial function, ultra-low resections with distal
      margin at only 2 cm distally to the tumor, role of mesorectum as preferential
      site of lymphatic diffusion, preservation of lombo-aortic and pelvic nerves.
      Laparoscopy is showing good results in bowel surgery so as previously got on
      biliary tract: less visceral manipulation, less stimulation of immunologic
      system, less pain, early resumption of peristalsis and food intake, better
      recovery, less hospital stay. We experimented on pig ultra-low laparoscopic
      resection of the rectum, with preservation of sfincterial function, and
      mechanical anastomosis at the upper edge of the sfincterial ring. The evaluation
      of surgical technique, post-operative supervision, and follow-up instrumental
      control (anal manometry, endo-rectal ultrasonography, sfincterial
      electtromanometry, Rx barium enema) show technical feasibility and confirm a
      better recovery with regular defecatory function.

PMID- 9019998
TI  - Regulation of malate synthase activity.

PMID- 9019999
TI  - Antioxidant enzymes in peroxisomes: effect of ischemia.

PMID- 9020000
TI  - A new evaluation of peroxisome proliferation in rainbow trout hepatocytes in
      culture.

PMID- 9020001
TI  - [Distal detubularized sigmoidoplasty. Description of the technique].
AB  - OBJECTIVES: To describe a new technique for orthotopic bladder replacement using
      a short detubularized segment of the most distal portion of the sigmoid colon,
      termed "detubularized distal sigmoidoplasty'. METHODS: The surgical technique
      utilized 1) large bowel to provide a larger intestinal lumen, stronger muscle
      layer and minimum metabolic activity; 2) a short segment providing adequate
      volume in the sigmoid and a reduced surface of exchange; and 3) a distal segment
      close to the urethra so it can be easily advanced without stretching and with
      minimum sectioning of the mesosigmoid. A short segment (approximately 18 cms) of
      the distal sigmoid is separated with minimum mobilization of the mesentery. It is
      detubularized to obtain a centrally located rectangle. The ureter is reattached
      using the antireflux technique of direct retrograde submucosal tunneling with a
      symmetrical pseudotrigonal arrangement. The reservoir is constructed using a
      single transverse continuous suture that is interrupted 2 cms before complete
      closure of the neobladder to provide an orifice for urethral anastomosis.
      RESULTS: The technique is simple and utilizes a segment shorter than those
      described to date. Any segment of the sigmoid can be utilized. The neobladder can
      be shaped with a single continuous suture and the ureter can be reinserted in a
      more anatomic position. The reservoir has an adequate volume of approximately 300
      cc. Voiding is accomplished by contraction of the reservoir and abdominal
      pressure. CONCLUSIONS: This neobladder technique is simple. It achieves excellent
      diurnal continence and maintains the contractile capacity which permits
      comfortable and compensated voiding.

PMID- 9020002
TI  - [Chronic prostatic inflammation: a confounding factor in the diagnosis of
      prostatic cancer].
AB  - OBJECTIVES: To evaluate the influence of inflammatory foci of the prostate on the
      efficacy of PSA and transrectal ultrasound in the diagnosis of prostatic cancer.
      METHODS: Ultrasound-guided transrectal biopsy was performed in 399 patients. The
      results of serum PSA, PSA density and ultrasound characteristics were compared
      with the pathological findings. RESULTS: The mean prostatic volume was greater in
      the cases with BPH and chronic inflammatory foci than those with prostatic cancer
      (p < 0.001). Twenty percent of the patients showed suspicious areas vs 75.1% of
      the cancers (< 0.001); 66.7% of those with chronic inflammatory foci showed
      classifications vs 40.6% of the cancers (p < 0.001). The patients with chronic
      inflammatory foci had PSA values that fell in between those of the BPH and cancer
      groups (p < 0.05). PSA density also showed intermediate values, although they
      were not significantly different. CONCLUSIONS: The presence of chronic prostatic
      inflammatory foci can increase serum PSA levels. To date, it is not possible to
      identify this group of patients to avoid a biopsy.

PMID- 9020003
TI  - [Urethral condyloma in the male: experience with 48 cases].
AB  - OBJECTIVES: To review our experience in the diagnosis and treatment of urethral
      condylomata. METHODS: From June, 1977 to November, 1994, 64 patients with
      condyloma acuminatum were treated at our institution. Forty-eight cases who had
      received no previous treatment were analyzed. The main reason for consultation
      was the appearance of an exophytic lesion in the meatus. Most of the condylomata
      were located in the navicular fossa. Treatment was by electrocoagulation in 24
      patients, photocoagulation with the Nd:YAG laser in 21 and other treatment
      modalities were utilized in 3 patients. To determine the incidence of recurrence
      and response to therapy, we analyzed the data of 34 patients with a minimum
      follow up of 2 months and a mean of 16 months. RESULTS: 36% had associated
      cutaneous condylomata. Urethroscopy detected 14.2% of the lesions that were
      undetectable by eversion of the meatus. Recurrence was observed in 35.2%. There
      were no differences for recurrence or complications between patients submitted to
      electrocoagulation and those who were treated by laser photocoagulation.
      CONCLUSIONS: Condyloma acuminatum of the urethra is uncommon. Urethroscopy is
      useful in making the diagnosis and for post-treatment follow up control
      evaluation. Electrocoagulation and Nd:YAG laser photocoagulation are useful in
      the treatment of this condition. Recurrence is frequently observed in patients
      with extensive lesions.

PMID- 9020004
TI  - [Premalignant and benign lesions in nodules of adenomatous hyperplasia].
AB  - OBJECTIVES: Currently, two premalignant lesions have been recognized: prostatic
      intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). Due
      to the possible clinical implications of these lesions, we attempted to determine
      their incidence in specimens of benign prostatic hyperplasia (BPH), the most
      frequent pathology of the prostate. METHODS: A pathological and
      immunohistochemical study using several markers was performed to detect
      premalignant lesions in 156 specimens obtained by adenomectomy and TUR from 1990
      to 1992. RESULTS: 20 PIN and 8 AAH (20.6%) were found. There were other equivocal
      prostatic lesions, not only with respect to premalignant lesions but prostatic
      carcinoma as well. CONCLUSIONS: Premalignant lesions within BPH nodules are
      frequent (20.6%). Furthermore, other lesions were also found that caused
      difficulty in making the differential diagnosis.

PMID- 9020006
TI  - [Identification of factors conditioning urinary cytology in bladder cancer].
AB  - OBJECTIVES: To identify the clinical and tumoral aspects related with urinary
      cytology as a means of validating current criteria or determining the usefulness
      of this test in the diagnosis of bladder tumors. METHODS: 96 patients that were
      posteriorly diagnosed as having primary transitional cell carcinoma of the
      bladder were initially evaluated by urinary cytology. The diagnoses were
      positive, negative or inconclusive cytology. Any abnormality (for both
      inconclusive and positive cytologies) were considered as compatible with tumor.
      To determine the relationship between patient characteristics and tumors, and the
      results of cytology, standard univariate statistical analysis was performed. To
      eliminate the confounding factors, a multivariate analysis was performed.
      RESULTS: Cytology was positive on 44 (45.8%), inconclusive on 22 (23%) and
      negative on 30 (31.2%) occasions. Age > or = 55 years (p < 0.05), grade (p <
      0.05), tumor aspect (p < 0.01) and size (p < 0.001) were associated with a higher
      frequency of cytologies compatible with tumor. Multiple regression analysis
      identified tumor size as the only independent variable related with the
      cytologies compatible with tumor [odds ratio = 8.68 (2.7-26.9)]. CONCLUSIONS: If,
      as the results of the present analysis suggest, the real effect of cytological
      analysis in the initial diagnosis of bladder tumors is the anticipation of
      different features of tumor grade and stage (as patient age, tumor size, aspect
      and number), its utility would be very limited since other more precise tests
      (US, cystoscopy...) that provide this information are available.

PMID- 9020005
TI  - [Results of a prospective study of chemoprophylaxis with alternating mitomycin-C
      and BCG: complete response and recurrence and progression index].
AB  - OBJECTIVES: The high incidence of recurrence in superficial urothelial cancer
      warrants the use of chemoprophylaxis; however, the results achieved to date have
      been unsatisfactory. The present study investigated the possibility of reducing
      the incidence of recurrence of superficial urothelial cancer post-TUR and disease
      progression. METHODS/RESULTS: 99 patients were treated with monthly instillations
      of mitomycin-C and BCG alternately for one year, which commenced three weeks
      following TUR. The incidence of recurrence and progression were 15.3% and 5.10%,
      respectively. Treatment was well-tolerated and there were minimum side effects.
      CONCLUSIONS: Chemoprophylaxis with alternating mitomycin-C and BCG therapy in
      patients with superficial urothelial cancer achieves good results. It is well
      tolerated and few side effects were observed.

PMID- 9020007
TI  - [Approximation to conservative surgery of Leydig cell tumor].
AB  - OBJECTIVES: To analyze the clinical and histological characteristics of 5 cases
      of Leydig cell tumor in order to establish the criteria for conservative surgical
      management. METHODS: Of 31 testicular tumors diagnosed from 1982-1993, 5(16.1%)
      were Leydig cell tumors. We analyzed patient general characteristics, the
      prevalent feminizing (60%) and hypogonadal features and the histopathological
      characteristics that might indicate a non aggressive course of the tumor.
      RESULTS: No metastasis was observed at 522.9 months mean follow up. Three
      patients underwent orchidectomy through the inguinal approach; one case had been
      incidentally discovered after subalbuginea resection due to a disseminated
      prostatic carcinoma and the fifth patient was treated conservatively by
      tumorectomy and is tumor-free at more than 120 months follow up. CONCLUSIONS:
      Parenchyma-sparing surgery may have a place in the treatment of interstitial cell
      tumor, with evident endocrinological and psychological benefits, especially in
      the young males that meet the clinical and histological criteria for conservative
      surgical management.

PMID- 9020008
TI  - [Hyperoxaluria and renal calculi].
AB  - Urolithiasis is one of the most frequent causes of morbidity in developed
      countries and its incidence is close to 5%. In our experience, 67.4% of urinary
      stones contain calcium oxalate as the main component, and hyperoxaluria plays an
      important role in the pathophysiology of this type of stone. The mechanisms
      responsible for the increment in urinary excretion of oxalate could involve
      oxalic acid synthesis. This increase could be due either to an increment of its
      endogenous formation or to an exogenous load of its precursors. Furthermore, an
      increased intestinal oxalate absorption is a frequent cause of hyperoxaluria and
      urolithiasis. Ingestion of oxalate rich foods, imbalance in the supply of other
      nutrients that influence oxalic acid absorption and GI disorders with
      malabsorption and/or decreased degradation of intraluminal oxalate can increase
      intestinal oxalate transport and cause hyperoxaluria. In this article we review
      the physiological mechanisms that control the oxalate pool: endogenous synthesis,
      exogenous supply, intestinal absorption and renal excretion of oxalic acid. We
      analyze the causes and the pathophysiological mechanisms that increase urinary
      oxalate excretion. We describe a protocol for the biochemical study of patients
      with hyperoxaluria and the therapeutic measures to reduce urinary oxalate are
      reviewed. Finally, possible research that may provide further insight into
      oxalate metabolism in patients with hyperoxaluria are discussed.

PMID- 9020009
TI  - [Insufficient detrusor contractility: a urodynamic and morphologic entity in
      prostatism].
AB  - OBJECTIVES: To analyze the urodynamic and ultrastructural characteristics of
      impaired detrusor contractility in patients with prostatism in comparison with
      lower urinary tract obstruction. METHODS: The study comprised 200 male patients
      (mean age 65.3 years) with prostatism submitted to a complete urodynamic study.
      An ultrastructural study was randomly performed in 40 patients and analyzed 600
      detrusor muscle images to determine the smooth muscle cell and interstitial
      changes. Detrusor urodynamics were compared with the ultrastructural cell and
      interstitial changes of the bladder smooth muscle. RESULTS: Urinary symptoms or
      free flowmetry alone failed to predict detrusor urodynamics. Urodynamic diagnosis
      was based on the detrusor pressure-flow study. We observed ultrastructural
      degenerative cell changes with statistical significance in impaired detrusor
      contractility such as no branching and intertwining of cells, absence of
      caveoles, perinuclear degeneration with vacuolization, destructured myofilament
      system with diminished anchorage plates and collagen infiltrating the
      interstitium with loss of bladder muscle fascicle organization. CONCLUSIONS:
      Impaired detrusor contractility is a urodynamic diagnosis that should be taken
      into account in patients with prostatism. The diagnosis of this condition
      requires performing a pressure-flow study. Impaired detrusor contractility showed
      a morphological and ultrastructural correlation with degenerative changes of the
      bladder muscle.

PMID- 9020010
TI  - [Intravaginal ultrasonography in the diagnosis of stress urinary incontinence].
AB  - OBJECTIVES: This analyzes the usefulness of transvaginal endosonography before
      and after surgery in patients with stress urinary incontinence. METHODS: We
      evaluated the bladder contour in 50 patients by transvaginal endosonography and
      the distance from the bladder neck to the pubis was measured with and without
      stress. If the distance was greater than 1 cm, it was presumed that the patient
      had stress urinary incontinence. RESULTS: In these 50 patients, the distance
      between the bladder neck and the pubis without stress ranged from 15 mm to 28 mm
      (mean 32 mm). In 47 patients (94%), we observed a displacement of the bladder
      base and neck to the pubis greater than 1 cm, indicating stress urinary
      incontinence. Transvaginal endosonography was performed four weeks later and
      proved to be useful in patient evaluation postoperatively, regardless of the
      surgical technique utilized. CONCLUSIONS: Transvaginal endosonography is a useful
      in the preoperative evaluation of patients with stress urinary incontinence and
      in evaluating the results of colposuspension.

PMID- 9020011
TI  - [Endourologic complication: endourologic resolution].
AB  - OBJECTIVES: To report an uncommon endourological complication that was also
      resolved by endourological methods. METHODS/RESULTS: We report on a patient with
      a right solitary kidney, radiolucent renal stone and an indwelling double-J
      catheter. While removing the double-J catheter after ESWL, it broke at the level
      of its distal third. The proximal two thirds remaining in the ureter were
      successfully removed by ureteroscopy after several attempts by ureteroscopy and
      percutaneous nephroscopy. CONCLUSIONS: Except for special circumstances, most of
      the endourological complications can be resolved by an endourological procedure.

PMID- 9020012
TI  - [Treatment of ureteral lithiasis with lithoclast: analysis of our experience].
AB  - OBJECTIVES: To analyze the role and the results achieved with the Lithoclast in
      the treatment of distal ureteral calculi in the era of ESWL. METHODS: From March,
      1994 to April, 1995, 41 patients with ureteral calculi were treated by
      ureteroscopy and direct stone fragmentation with the Lithoclast. RESULTS: 90% of
      the patients were stone-free one month after treatment; 3 patients in whom stone
      fragmentation could not be achieved required ESWL; one patient required open
      surgery for ureteral detachment. CONCLUSIONS: Ureteroscopy and stone
      fragmentation with the Lithoclast is a good, inexpensive mode of treatment of
      ureteral stones and is particularly indicated as the first mode of treatment in
      those centers, like ours, where ESWL is unavailable.

PMID- 9020013
TI  - [Renal incidentaloma and pregnancy].
AB  - OBJECTIVES: To report a case of a renal mass that had been incidentally
      discovered during the first month of pregnancy. METHODS: The difficulties in
      determining the nature of such masses when they are small and the appropriate
      timing for surgical intervention are discussed. RESULTS: A presumptive diagnosis
      of angiomyolipoma was made from the findings of the imaging techniques,
      especially Doppler ultrasound. Histological examination confirmed the diagnosis.
      CONCLUSIONS: Ultrasound evaluation during pregnancy may incidentally discover an
      undetected pathology and should therefore systematically include the entire
      abdominal cavity. It is difficult to determine the appropriate time for surgery.

PMID- 9020014
TI  - [Verrucous carcinoma of the penis: report of two cases].
AB  - OBJECTIVES: Verrucous carcinoma, a variant of squamous cell carcinoma accounts
      for 5%-8% of all penile tumors. The unique histological features and behaviour of
      this tumor type prompted us to report these two cases.

PMID- 9020015
TI  - [Synchronous multiple renal carcinoma. Review of the literature and report of a
      new case].
AB  - OBJECTIVES: Herein we describe an additional case of bilateral multiple renal
      cell carcinoma, a rare condition outside the context of phacomatosis.
      METHODS/RESULTS: A 57-year-old man presented with asymptomatic hematuria. He had
      no other remarkable medical or urological history. Radiological evaluation
      disclosed multiple tumors in both kidneys that required bilateral nephrectomy.
      CONCLUSION: Multiple syncronous renal cell carcinoma has been described in Von
      Hippel Lindau disease or the polycystic conditions of chronic renal failure. A
      few cases have been reported in patients who did not have the foregoing
      conditions or were asymptomatic as the case described herein, who required
      bilateral nephrectomy.

PMID- 9020016
TI  - [Gynecomastia and Leydig cell tumor, clinically occult].
AB  - OBJECTIVES: An uncommon case of clinically occult Leydig cell tumor of the testis
      is described. The literature is reviewed with special reference to the difficulty
      encountered in making the diagnosis. METHODS/RESULTS: The clinical data of a
      patient with occult Leydig cell tumor of the testis, whose only remarkable
      feature was a long history of gynecomastia, are presented. CONCLUSIONS: A
      hormonal study and scrotal ultrasound evaluation are essential in the diagnosis
      of this tumor type and should be performed even in the absence of testicular
      anomalies on palpation.

PMID- 9020017
TI  - [Renal hemangiopericytoma and secondary hypertension].
AB  - OBJECTIVES: Tumors arising from pericytes are rare; even more so are those
      located in the kidney. A case of renal hemangiopericytoma is described herein.
      The literature is reviewed with special reference to the unclear prognosis of the
      foregoing condition and the therapeutic approach. METHODS: A 51-year-old male
      with renal hemangiopericytoma who underwent radical nephrectomy is described.
      RESULTS/CONCLUSIONS: The arterial hypertension that had led to the diagnosis of
      this neoplasm remitted after surgery and can be considered to be a paraneoplastic
      manifestation.

PMID- 9020018
TI  - [Perineal neurilemmoma].
AB  - OBJECTIVES: Neurilemoma or Schwannoma is a rare benign tumor which may affect any
      nerve of the body. Genitourinary involvement is rare. Herein we describe a case
      of neurilemoma of the perineum. To our knowledge, only one case involving this
      site has been previously described in the literature. METHODS/RESULTS: We report
      on a patient with an asymptomatic, solitary perineal tumor. The presumptive
      diagnosis of a benign tumor was made on the basis of the ultrasound and CT
      findings. Pathological analysis disclosed the typical Verocay bodies of a
      neurilemoma. CONCLUSIONS: The treatment of choice is by simple surgical excision.
      Tumor recurrence is rare.

PMID- 9020019
TI  - Experimental study of ureteral free grafts. II. Urographic findings of integrated
      graft.
AB  - OBJECTIVE: An experimental study was conducted in rats to assess urographically
      the function of the integrated autologous free graft (IAFG) of the ureter, in
      which the ureter is reimplanted after being extracted from the animal's body and
      involves complete devascularization and ureteral ischemia. METHODS: The technique
      employed included direct vascular injection of contrast (iliac vein). The 40 rats
      were randomly distributed into three groups: NU group (n = 20), normal ureter; SC
      group (n = 15), surgical control, only ureterolysis; RU group (n = 14),
      reimplanted ureter as IAFG. RESULTS: The results show the urographic
      characteristics of the normal ureter (NU). The SC group IVUS were not distinct
      from those of the NU group. In the RU group, the segment of the ureter used as
      IAFG showed a normal or abnormal urographic image, depending on the result of the
      anastomosis. No ureteral fistula or leakage was observed in the urograms.

PMID- 9020020
TI  - Telomere crisis, the driving force in cancer cell evolution.
AB  - Cancer cells show characteristic telomere dynamics. Their chromosomes usually
      have short telomeres and a high telomerase activity. The "telomere crisis model"
      proposed here suggests that these unique telomeric features are responsible for
      the progression of cancer.

PMID- 9020021
TI  - Identification of a human cDNA homologue to the Drosophila translocation protein
      1 (Dtrp1).
AB  - In yeast, several integral membrane proteins such as Sec61p, Sec62p and Sec63p
      have been reported as the components involved in protein translocation across and
      into the endoplasmic reticulum (ER) membrane. Among them, the homologues of
      Sec61p have been found both in bacterias and mammals, whereas those of Sec62p or
      Sec63p have not. So, Sec61p seem to be the evolutionary conserved component,
      while Sec62p and Sec63p may not. To date, no homologues of Sec62p have been found
      in mammals yet. Here, we report a novel human cDNA, HTP1 (for human translocation
      protein 1), that encodes a protein of 399 amino acids that is 36.3% identical
      (64.6% similar) to Drosophila homologue of Sec62p, Drosophila translocation
      protein 1 (Dtrpl). Northern blot analysis showed two HTP1 transcripts of about
      2.8 and 5.5 kb, which were expressed concomitantly in various human tissues such
      as heart, brain, placenta, liver and pancreas.

PMID- 9020022
TI  - Cell cycle-dependent regulation of the mouse DNA topoisomerase IIalpha gene
      promoter.
AB  - Expression of DNA topoisomerase (topo) IIalpha varies through the cell cycle with
      its peak in G2/M. To investigate the mechanism controlling the topo IIalpha gene
      expression, we cloned the 5' upstream region of the mouse topo IIalpha gene.
      Although there was no TATA-like sequence, two GC and seven CCAAT boxes were found
      in the upstream region 5' distal to the major transcription start sites, which
      were located 137, 124, and 105 bp upstream from the ATG start codon. Luciferase
      vectors with the upstream sequences were constructed and transfected into HeLa
      cells, followed by cell cycle arrest either in G1 by treatment with mimosine, in
      S with thymidine, or in G2/M with colcemid. We found that the topo IIalpha gene
      promoter has the cell cycle-dependent activity, which is low in G1, rises in S,
      and peaks in G2/M. We suggest that the level of topo IIalpha mRNA is determined
      by the cell cycle-regulated promoter.

PMID- 9020023
TI  - Concordant induction of prostaglandin E2 synthase with cyclooxygenase-2 leads to
      preferred production of prostaglandin E2 over thromboxane and prostaglandin D2 in
      lipopolysaccharide-stimulated rat peritoneal macrophages.
AB  - Rat peritoneal macrophages were stimulated with lipopolysaccaride (LPS) for
      various periods and their ability to convert exogenous arachidonic acid to
      various prostanoids was examined. Unstimulated cells, which expressed
      cyclooxygenase (COX)-1 but not COX-2, produced thromboxane (TX) B2 >
      prostaglandin (PG) D2 > PGE2, whereas cells stimulated for 6-12 h with LPS
      exhibited marked increase in conversion to PGE2, which paralleled COX-2
      induction, with minimal change in conversion to TXB2 and PGD2. Pharmacological
      studies showed that formation of PGE2 was mediated predominantly by COX-2, PGD2
      by COX-1, and TXB2 by both COX-1 and COX-2 depending upon the timing of LPS
      stimulation. Measurement of the conversion of exogenous PGH2 to each prostanoid
      in cell lysates demonstrated LPS-dependent increase in PGE2 synthase activity
      that was degenerated by pretreatment with actinomycin D or cycloheximide. Thus,
      concordant induction of terminal PGE2 synthase with COX-2 leads to the preferred
      production of PGE2 to TXB2 and PGD2 by LPS-stimulated macrophages.

PMID- 9020024
TI  - Reactive oxygen species participate in peroxynitrite-induced apoptosis in HL-60
      cells.
AB  - Peroxynitrite (ONOO-) is a physiological product generated by the interaction of
      superoxide (O2.-) and nitric oxide (.NO). We have previously shown that
      peroxynitrite induces apoptosis in HL-60 cells. In the present study, we
      demonstrated that peroxynitrite generates reactive oxygen species (ROS) in HL-60
      cells. Brief exposure of HL-60 cells to ONOO- induced elevation of lucigenin
      chemiluminescence, indicating generation of superoxide anion. Exogenous
      superoxide dismutase (SOD), a scavenger of O2.-, fully abolished the
      chemiluminescence response, further supporting this notion. Following O2.-
      generation, the accumulation of hydrogen peroxide (H2O2) was observed. The
      addition of SOD exacerbated but that of catalase attenuated peroxynitrite-induced
      DNA fragmentation, suggesting that this H2O2 production contributes to the
      apoptotic process. In addition, pre-treatment of HL-60 cells with N-acetyl-L
      cysteine (15 mM), a ROS scavenger, fully scavenged peroxynitrite-elicited ROS
      generation and effectively inhibited (ONOO-)-induced apoptosis, further enforcing
      this hypothesis. In summary, our results suggest that (ONOO-)-stimulated ROS
      formation may serve as a mechanism for the propagation of peroxynitrite-mediated
      apoptotic cell death in an intact cell system.

PMID- 9020025
TI  - Tumor necrosis factor alpha alters the cytotoxic effect of hydrogen peroxide in
      cultured hepatocytes.
AB  - We examined whether tumor necrosis factor-alpha (TNF) affects the cytotoxic
      capacity of reactive oxygen species on rat hepatocytes in culture. Both TNF and
      reactive oxygen species are involved in many inflammatory events including
      hepatic ischemia/reperfusion injury and endotoxic shock. Synchronous treatment of
      hepatocytes with both TNF and H2O2 demonstrated that TNF (2000 ng/ml) enhanced
      the cytotoxic effect of H2O2 (500 microM). By contrast, pretreatment with TNF
      (2000 ng/ml) for 24 h followed by exposure to H2O2 (1000 microM) reduced the
      reactive oxygen-induced cytotoxicity. We conclude that TNF increases the effects
      of reactive oxygen-induced cytotoxicity when exposed synchronously, whereas TNF
      pretreatment induces a cytoprotective effect to reactive oxygen species,
      presumably by up-regulation of the reduced form of glutathione levels in
      hepatocytes.

PMID- 9020026
TI  - A novel antiallergic drug epinastine inhibits IL-8 release from human
      eosinophils.
AB  - Eosinophils are believed to be one of the important sources of cytokines at the
      site of allergic inflammation. A novel antiallergic agent epinastine showed a
      dose- and time-dependent suppressive effect on IL-8, one of the chemokines for
      eosinophils, released from eosinophils isolated from atopic diseases. The time
      dependent accumulation of IL-8 inhibited by cycloheximide and the evaluation of
      the IL-8 mRNA levels by reverse transcriptase-polymerase chain reaction suggested
      that its action occurred in the posttranscriptional processes. It was suggested
      that epinastine might prevent the autocrine cycle for recruitment of human
      eosinophils by inhibiting IL-8 release from these cells.

PMID- 9020027
TI  - Expression and induction by IL-6 of the normal and variant genes for human
      plasminogen.
AB  - We examined the promoter activity of the gene for human plasminogen (PLG)
      employing its 1.1 kb fragment of the 5'-flanking region inserted in front of a
      reporter gene. Deletion analysis revealed that a region surrounding the
      transcription start site was essential for the PLG expression. Since the PLG gene
      has three sequences for the interleukin-6 (IL-6) responsive element, we examined
      the effect of IL-6 on the PLG expression. IL-6 stimulation of PLG resulted in a
      2.5-fold increase in its transcription. This is also true for the PLG gene of a
      case with dysplasminogenemia. Although the patient's gene had six mutations in
      the 5'-flanking region, its promoter activity was 1.8-fold that of normal PLG.

PMID- 9020028
TI  - Purification of streptodornase from Streptococcus equisimilis and its DNA-induced
      conformational change.
AB  - Extracellular streptodornase was purified from fermentation media of
      Streptococcus equisimilis by stepwise carboxymethyl-Sepharose column
      chromatography. The active enzyme fraction was eluted with phosphate buffer
      containing 0.2 M NaCl. The purified enzyme showed a homogeneity on SDS-PAGE and
      had a subunit molecular weight of 35 kDa. Conformational change of streptodornase
      by binding to calf thymus DNA was examined by circular dichroism (CD). CD study
      clearly showed a DNA-induced conformational change in the secondary structure of
      streptodornase, resulting in a decrease of alpha-helical content of the enzyme.

PMID- 9020029
TI  - Circular dichroism spectra of calcium channel antagonist omega-conotoxins.
AB  - The circular dichroism (CD) spectrum of omega-conotoxin GVIA is quite different
      from those of omega-conotoxin MVIIA and MVIIC, despite their distinct similarity
      in three dimensional structures. In order to characterize the unique CD spectrum
      of omega-conotoxin GVIA, we focused our attention on the aromatic chromophore and
      analyzed the CD spectra of three synthetic analogs, in which Tyr13, Tyr22, and
      Tyr27 were individually replaced by alanine. Replacement of Tyr27 caused a
      significant change in both the near- and far-ultraviolet CD spectrum of omega
      conotoxin GVIA and resulted in the omega-conotoxin MVIIA/MVIIC-like pattern,
      suggesting that Tyr27 has a dominant contribution to the unique CD profile of
      omega-conotoxin GVIA.

PMID- 9020030
TI  - Major role of the histones H3-H4 in the folding of the chromatin fiber.
AB  - We have characterized the hydrodynamic behavior of nucleosome arrays in which the
      N- and C-terminal "tails" of the histone H2A-H2B and H3-H4 domains have been
      selectively removed by digestion with immobilized trypsin. The sedimentation
      coefficient of the polynucleosome fibers lacking the histone H2A-H2B tails
      exhibited a salt dependence close to that of the non-trypsinized nucleosome
      arrays. In contrast, the salt-dependent behavior of the H3-H4-trypsinized
      polynucleosome fibers was found to be closer to that observed for the nucleosome
      arrays on which all the histones were trypsinized. This indicates that the N- and
      C-terminal domains of histones H3-H4 play a major role in the folding of the
      chromatin fiber. Magnesium titration of the polynucleosome fibers consisting of
      these trypsinized histone octamer hybrids at low ionic strength indicates that
      the histone H3-H4 tails also play an important role in the association of the
      polynucleosome fibers. These findings suggest that, after linker histones
      (histones of the H1 family), the tails of the histone H3-H4 domains are the major
      players in the processes that lead to the intra-association (folding) and inter
      association of the chromatin fiber.

PMID- 9020031
TI  - Reversible inhibition of lambda exonuclease with high pressure.
AB  - The hydrolytic activity of lambda exonuclease, a highly processive enzyme, is
      inhibited by high pressure. When assayed at 67 MPa, the activity is 87% of the
      atmospheric rate; increasing the pressure to 336 MPa causes a greater than 99%
      inhibition of the enzyme activity. Decreasing the pressure from 336 MPa to 67 MPa
      at 20 degrees C reverses the inhibition. The use of hydrostatic pressure to
      control the activity of lambda exonuclease has potential practical application in
      DNA sample preparation, analysis, and sequencing.

PMID- 9020032
TI  - Processing properties of recombinant human procathepsin L.
AB  - Human procathepsin L is highly expressed in mouse myeloma cells and processed
      into the mature enzyme under the acidic condition below pH 5.5. Different from
      the mature enzyme, it is stable at a neutral pH. To examine whether or not
      procathepsin L is autoprocessed intramolecularly, we constructed a mutant
      procathepsin L cDNA in which the codon for Cys138 proposed as the active site was
      mutated to encode Ser by PCR-mutagenesis. The mutant procathepsin L (C138S) was
      secreted into the culture medium from mouse myeloma cells expressing this mutant
      cDNA, but not processed into the mature form under the acidic condition. In
      addition, the mutant C138S was not processed by the incubation at 37 degrees C
      with wild-type procathepsin L or mature cathepsin L under the acidic condition.
      These findings showed that Cys138 is the active site of cathepsin L and that the
      autocatalytic processing occurs intramolecularly.

PMID- 9020033
TI  - Molecular cloning and characterization of a putative neural calcium channel
      alpha1-subunit from squid optic lobe.
AB  - The complete amino acid sequence of a putative calcium channel alpha1-subunit,
      SQCC1, from the optic lobe of the squid Loligo bleekeri has been deduced by
      cloning and sequence analysis of the complementary DNA. The open reading frame
      encodes 2206 amino acids, which corresponds to a molecular weight of 251,451. The
      deduced amino acid sequence shares general structural features with the other
      voltage-dependent calcium channels; it consists of four repeated units of
      homology. Each motif has five hydrophobic segments and one positively charged
      segment. The transcriptional products were detected in all nervous systems
      examined; optic lobe, cerebral ganglia and giant stellate ganglia. However, it
      was not detected in the mantle muscle, heart and stomach, indicating SQCC1 is a
      calcium channel alpha1-subunit specific for squid nervous system. SQCC1 is more
      closely related in its amino acid sequence patterns to dihydropyridine
      insensitive calcium channels rather than dihydropyridine-sensitive ones.

PMID- 9020034
TI  - PPAR alpha mediates peroxisome proliferator-induced transcriptional repression of
      nonperoxisomal gene expression in mouse.
AB  - The strain difference, peroxisome proliferator specificity and role of PPAR alpha
      in peroxisome proliferator-induced transcriptional repression of nonperoxisomal
      transthyretin and alpha2u-globulin genes were examined. The genes were repressed
      by four peroxisome proliferators in all seven mouse strains tested. The extent of
      repression was strongly dependent on both the mouse strains and type of
      proliferator, although the mRNA levels of PPAR alpha and its partner in
      heterodimerization, RXR alpha were not different. The role of PPAR alpha in
      repression was confirmed by the finding that PPAR alpha-null mice were not
      responsive to transcriptional repression. These results indicate that PPAR alpha
      plays an obligatory role in transcription of various genes, some of which are not
      related to lipid metabolism.

PMID- 9020035
TI  - Activation of the metallothionein-I gene promoter in response to cadmium and USF
      in vitro.
AB  - To elucidate the molecular mechanism of metallothionein (MT) gene activation in
      response to various inducers, we constructed a G-less mouse MT-I promoter and
      transcribed in HeLa nuclear extract. The MT-I gene was transcribed efficiently in
      this extract and initiation of transcription occurred at the correct site (+1).
      Transcription of the MT-I gene was stimulated three- to fivefold in the nuclear
      extract from the cadmium-treated cells relative to the extract from the untreated
      cells. The MT-I promoter was also activated three- to fourfold by recombinant
      USF1, a helix-loop-helix-leucine zipper DNA binding transcription factor that
      recognizes the major late transcription factor (MLTF) binding site on the MT-I
      promoter. To our knowledge, this is the first report of the activation of MT-I
      promoter in vitro by a toxic metal and by the transcription factor USF.

PMID- 9020036
TI  - Distinct sequences of AKH/RPCH family members in beetle (Scarabaeus-species)
      corpus cardiacum contain three aromatic amino acid residues.
AB  - Two forms of AKH/RPCH family peptides have been identified from the corpus
      cardiacum of various dung beetle species of the genus Scarabaeus and the related
      genus Gareta by using RP-HPLC. The primary structures were established in two
      species by automated Edman degradation and mass spectral analysis as blocked
      octapeptides containing three aromatic amino acids (at positions 2, 4 and 8):
      peptide I: pGlu-Phe-Asn-Tyr-Ser-Pro-Asp-Trp-NH2; peptide II: pGlu-Phe-Asn-Tyr-Ser
      Pro-Val-Trp-NH2. The peptides were not active in the heterologous adipokinetic
      bioassay in locusts, but increased the concentration of proline in the haemolymph
      of Scarabaeus beetles. Since proline is also used in these species to provide the
      energy for contraction of the flight muscles during flight, it is proposed that
      the distinct peptides characterized here are responsible for the hormonal control
      of proline homeostasis.

PMID- 9020037
TI  - Sequencing, analysis and expression in Escherichia coli of a gene encoding a 15
      kDa Cryptosporidium parvum protein.
AB  - A previous paper presented data on a cDNA sequence encoding a protein associated
      with the AIDS related pathogen, Cryptosporidium parvum. However, the position of
      the start codon was uncertain, and the 5' end was continuous, lending doubt about
      the size and complete sequence of the final protein product. Herein we present
      the complete gene sequence and conclude the predicted size of the putative
      protein to be 16.2 kDa.

PMID- 9020038
TI  - Novel gene expressed in spleen cells mediating acquired testosterone-resistant
      immunity to Plasmodium chabaudi malaria.
AB  - We report the identification of a novel mouse cDNA encoding IAP38, a putative
      plasma membrane protein of 38 kDa in splenic macrophages, B cells and T cells.
      The expression of iap38 is induced by blood-stage infections of Plasmodium
      chabaudi malaria and is testosterone-sensitive in non-immune mice. However, when
      mice have acquired testosterone-resistant immunity to P. chabaudi, there is an
      about 40-fold increase in the expression of iap38, which has then largely lost
      its responsiveness to infection and testosterone. The gene iap38 is suggested to
      be involved in imparting spleen cells the ability to mediate testosterone
      resistant immunity to P. chabaudi malaria.

PMID- 9020039
TI  - Dual inhibition of DNA topoisomerases of Leishmania donovani by novel indolyl
      quinolines.
AB  - omoindolyl)]ty of biologically active compounds contain indole and quinoline
      nuclei. A one step synthesis of some novel indolyl quinoline analogs e.g. 2-(2"
      Dichloro-acetamidobenzyl)-3-(3'-indolyl)-quinoline [1], 2-(2"-Dichloroacetamido
      5"-bromobenzyl)-3'-[3'-(5'-bromoindolyl  ] -6-bromo quinoline [2], and 2-(2"
      acetamido benzyl)-3-(3'-indolyl)-quinoline [3] has been developed under Friedel
      Crafts acylation conditions. The compounds inhibit the relaxation and
      decatenation reactions catalysed by type I and type II DNA topoisomerases of
      Leishmania donovani. Among the three synthetic indolyl quinolines, the Br
      derivative [2] is most active. The results reported here concerning the
      inhibition of type I and type II DNA topoisomerases indicate that the compounds
      act as "dual inhibitors" of the enzymes and can be exploited for rational drug
      design in human leishmaniasis.

PMID- 9020040
TI  - Angiotensin II stimulates the proliferation of osteoblast-rich populations of
      cells from rat calvariae.
AB  - We examined the effects of angiotensin II (Ang II) on the proliferation of
      osteoblast-rich populations of cells obtained from calvariae of newborn rat.
      Addition of Ang II to the culture medium caused dose-dependent increases in the
      rate of DNA synthesis. Such increases were completely inhibited by the addition
      of DuP753, an antagonist of AT1 receptor. Ang II potentiated the production of
      inositol 1,4,5-trisphosphate (IP3) in the culture. Ang II also stimulated the
      activities of mitogen-activated protein kinases (MAPKs) upon binding to the AT1
      receptor. These results suggest that Ang II might be intimately involved in the
      proliferation of the cells in calvariae through the AT1 receptor.

PMID- 9020041
TI  - Antipeptide antibodies as probes of subunit-dependent structural changes in the
      regulatory domain of the gamma-subunit of phosphorylase kinase.
AB  - The gamma-subunit of phosphorylase kinase contains a protein kinase catalytic
      domain (residues 20-276) and a regulatory domain (residues 276-386). The purpose
      of the present investigation was to develop monospecific antibodies against four
      synthetic gamma-subunit regulatory domain peptides (PhK1: 362-386; PhK5: 342-366;
      PhK9: 322-346; PhK13: 302-326) to use as probes to study the structure of the
      regulatory domain. Each affinity-purified antibody was characterized with regard
      to its ability to bind three different structural forms of the gamma-subunit: the
      isolated gamma-subunit, the gamma-delta complex, and the holoenzyme complex
      (alpha beta delta gamma)4. Of the four antibodies, binding of affinity-purified
      anti-PhK13 was most affected by alterations in gamma-subunit interactions. Taken
      together, the data from this investigation indicate that the regulatory domain of
      the gamma-subunit can assume different immunochemically distinguishable
      conformations as the result of interactions among the alpha-, beta-, gamma-, and
      delta-subunits of phosphorylase kinase.

PMID- 9020042
TI  - Antibodies to the HIV-1 p17 protein cross-react with human superoxide dismutase
      2.
AB  - Antibodies reacting with the gag protein p17 of the human immunodeficiency virus
      type 1 (HIV-1) can occasionally be found in the serum of non-HIV-1-infected
      individuals. Conversely, anti-p17 antibodies can also react with human tissues
      from non-infected individuals. Here we report on the isolation from human liver
      of a molecule that is immunoreactive with anti-p17 antibodies. This molecule was
      purified to homogeneity and identified as superoxide dismutase-2 (manganese type
      SOD). Both human SOD-2 and HIV-1 p17 contain the LQPALK hexapeptide which may
      serve as a common antigenic determinant. This study indicates that human SOD-2 is
      a target for anti-p17 antibodies and suggests that HIV-1-negative individuals may
      possess SOD-2 auto-antibodies that cross-react with HIV-1 p17.

PMID- 9020043
TI  - Identification of ecdysis-triggering hormone in the silkworm Bombyx mori.
AB  - Ecdysis, the shedding of cuticle at the end of each life stage, is critical to
      the postembryonic development of insects. The endocrine regulation of ecdysis has
      been highlighted by the recent description of the epitracheal endocrine system in
      the tobacco hornworm Manduca sexta, which produces ecdysis-triggering hormone
      (Mas-ETH). This peptide hormone initiates pre-ecdysis and ecdysis through a
      direct action on the central nervous system. Here we show that ETH
      immunoreactivity and ecdysis-triggering activity in epitracheal glands of the
      silkworm Bombyx mori are attributable to a 23 amino acid peptide, Bom-ETH. The
      complete amino acid sequence of Bom-ETH is SNEAFDEDVMGYVIKSNKNIPRM-NH2. Synthetic
      Bom-ETH was prepared and shown to be chemically and biologically identical to the
      native substance. Injection of Bom-ETH leads to pre-ecdysis and ecdysis in B.
      mori pharate larvae and pupae as well as comparable stages of M. sexta. Exposure
      of the isolated nervous system to Bom-ETH triggers pre-ecdysis and ecdysis burst
      patterns corresponding to the natural behavior. Bom-ETH belongs to an extended
      family of multifunctional neurohormones and hormones found in arthropods and
      molluscs.

PMID- 9020044
TI  - cDNA sequence analysis and expression of kappa-bungarotoxin from Taiwan banded
      krait.
AB  - The cDNAs encoding kappa-bungarotoxin was constructed from the cellular RNA
      isolated from the venom glands of Bungarus multicinctus by reverse transcription
      polymerase chain reaction. A high degree of nucleotide sequence homology was
      observed between kappa-bungarotoxin and other kappa-neurotoxins. The kappa
      bungarotoxin was subcloned into the expression vector pET32a(+) and transformed
      into BL21(DE3) E. coli strain. The recombinant toxin was expressed as a fusion
      protein. Recombinant kappa-bungarotoxin was separated from the fused protein by
      cleavage with CNBr and purified by reversed phase high performance liquid
      chromatography. In addition to kappa-bungarotoxin, the cDNA fragment encoding
      kappa3-bungarotoxin was also found in the cDNA mixtures prepared from the
      cellular RNA of the venom glands of the same snake. This result suggests that the
      venom glands of Taiwanese B. multicinctus should secrete at least two kinds of
      kappa-neurotoxins.

PMID- 9020045
TI  - Evidence supporting a signal transduction pathway leading to the radiation
      resistant phenotype in human tumor cells.
AB  - A signal transduction pathway, involving oncogenes and their normal counterparts
      the proto-oncogenes, analogous to that for cell growth and differentiation has
      been proposed to lead to the phenotype of cellular radioresistance (RR). In this
      report we provide evidence demonstrating the existence of such a pathway by using
      antisense oligonucleotides (ASO) to reverse the RR phenotype. Utilizing ASO
      directed against the raf-1 gene, a central component of this proposed pathway, we
      were able to reverse the RR phenotype of human tumor cell lines having elevated
      HER-2 expression or a mutant form of Ha-ras, two genes upstream of raf-1 in
      signal transduction. Additionally, anti-ras ASO were able to radiosensitize HER-2
      overexpressing cells. These results, which verify the presence of a signaling
      pathway leading to cellular RR, also have possible clinical implications for the
      use of ASO as a means to sensitize radioresistant tumors to radiation therapy.

PMID- 9020046
TI  - The recombinant catalytic domain of mouse collagenase-3 depolymerizes type I
      collagen by cleaving its aminotelopeptides.
AB  - The sequence coding for the catalytic domain of mouse collagenase-3 (MMP-13) was
      amplified by polymerase chain reaction and expressed in Escherichia coli. The
      recombinant catalytic domain (CCD), mainly recovered as inclusion bodies, was
      renatured and purified to homogeneity by preparative SDS-PAGE. The purified CCD
      degraded gelatin, casein and a synthetic peptide. CCD was not able to cleave the
      triple-helical domain of type I collagen but conserved the specific property of
      full-length collagenase-3 to cleave the N-telopeptides. These results show that
      residues involved in the recognition and cleavage of the aminotelopeptides of
      type I collagen are located in the catalytic domain of mouse collagenase-3 and
      that the C-terminal domain is not required for this activity.

PMID- 9020047
TI  - Actin enhances the activation of human neutrophil NADPH oxidase in a cell-free
      system.
AB  - The cell-free activation of human neutrophil NADPH oxidase (02- generating
      enzyme) was enhanced by exogenously added G-actin (actin monomer). When cytosol,
      a constituent of the system, was pretreated with DNase I, which may bind to G
      actin (endogenous) to block polymerization, the activation of NADPH oxidase was
      significantly suppressed. The activation was also impaired when cytosol G-actin
      was removed by DNase I-linked resin, being completely restored by the addition of
      G-actin. These results suggest a role of actin and its polymerization in the
      activation of NADPH oxidase of human neutrophils.

PMID- 9020048
TI  - Characterization of a fusion protein between human cytochrome P450 1A1 and rat
      NADPH-P450 oxidoreductase in Escherichia coli.
AB  - A cDNA of fusion protein between human cytochrome P450 1A1 and rat NADPH-P450
      reductase was genetically engineered and expressed in Escherichia coli DH5alpha
      cells under the control of an inducible tac promoter (Y. J. Chun, T. Shimada, and
      F. P. Guengerich, (1996) Arch. Biochem. Biophys. 330, 48-58). E. coli membranes
      of transformed cells showed much higher P450 1Al-dependent monooxygenase and
      NADPH-P450 reductase activities than pCW control vector or P450 1A1 expression
      vector-transformed cells. Ethoxyresorufin O-deethylase and methoxyresorufin O
      demethylase were 22-fold and 11-fold higher than the control activity,
      respectively. alpha-Naphthoflavone and beta-naphthoflavone strongly inhibited
      P450 1A1 activity of the fusion protein, with alpha-naphthoflavone being more
      potent than beta-naphthoflavone. Divalent cations (e.g. Ca2+ and Mg2+) increased
      P450 1A1 activity as well as NADPH-P450 reductase activity. These results
      demonstrate that this fusion protein in E. coli membrane may be a useful model
      for elucidating details of protein-protein interactions between P450 and NADPH
      P450 reductase in the endoplasmic reticulum of mammalian cells.

PMID- 9020049
TI  - Differentiation-dependent expression of a human carboxylesterase in monocytic
      cells and transcription factor binding to the promoter.
AB  - Carboxylesterases play an important role in defense and clearance mechanisms of
      the monocyte/macrophage system. During the differentiation process of cells from
      the monocytic cell line THP-1 we observed a transient transcriptional
      upregulation of a human carboxylesterase analyzed by means of Northern blots. In
      PMA-treated THP-1 cells we could detect three major transcription initiation
      sites as revealed by Nuclease Protection Assay carried out with two overlapping
      antisense RNA probes. We have recently cloned the carboxylesterase upstream
      sequence and showed its basal promoter activity in CHO cells. Using
      electrophoretic mobility shift analysis we demonstrated that the promoter region
      spanning base pairs -1 to -275, which contains several putative binding sites for
      transcription factors, is bound by nuclear factors Sp1 and IRBP but not by
      C/EBPs. Taken together these data indicate that carboxylesterase gene
      transcription in THP-1 cells starts at multiple initiation sites and that Sp1 and
      IRBP may be critical factors for modulating the differentiation-dependent
      transcription of this human carboxylesterase gene.

PMID- 9020050
TI  - Effect of ATP binding cassette/multidrug resistance proteins on ATP efflux of
      Saccharomyces cerevisiae.
AB  - Multidrug resistance (MDR) in mammalian tumors or tissues is often associated
      with the overexpression of the putative drug efflux pump P-glycoprotein (Pgp).
      One theory concerning the mechanism of Pgp activity is that efflux of ATP is
      coupled to drug efflux. Evidence in support of this theory has been observed in
      mammalian cells. Recently, the STS1 gene, which is a multidrug resistance gene
      related to the mammalian Pgp's, has been characterized in S. cerevisiae. Also,
      the mouse mdr3 Pgp has been functionally expressed in yeast cells. Therefore, it
      was of interest to determine whether the expression of these proteins affected
      ATP efflux from yeast. Although both genes were shown to confer MDR, thus
      confirming functional expression, the endogenous glucose-dependent, drug
      stimulated ATP efflux activity of yeast was not affected by expression of STS1,
      and was decreased by the expression of mouse mdr3.

PMID- 9020051
TI  - The gnd gene encoding a novel 6-phosphogluconate dehydrogenase and its adjacent
      region of Actinobacillus actinomycetemcomitans chromosomal DNA.
AB  - A 10-kb DNA fragment containing the gnd gene from Actinobacillus actinomy
      cetemcomitans Y4 was isolated and sequenced. The structural gnd gene codes for 6
      phosphogluconate dehydrogenase that consists of 484 amino acids. In contrast to
      the gnd gene in Escherichia coli, Salmonella typhimurium, or Klebsiella
      pneumoniae, the gnd gene of A. actinomycetemcomitans was not located in the rfb
      or cps operon. The zwf gene encoding glucose 6-phosphate dehydrogenase, which is
      another enzyme consisting of pentose-phosphate pathway, sided at 3.8-kb upstream
      from the gnd gene. A phylogenetic tree based on sequence analyses showed higher
      homology of 6-phospho-gluconate dehydrogenase of A. actinomycetemcomitans with
      the eucaryotic enzymes rather than with bacterial enzymes.

PMID- 9020052
TI  - Ribozyme and antisense RNAs inhibit coupled transcription translation by binding
      to rabbit polyribosomes.
AB  - The behavior of ribozyme and antisense RNAs was analyzed in a coupled rabbit
      reticulocyte transcription translation system. Both ribozyme and antisense RNAs
      were efficiently produced and bound tightly to polyribosomes at 30 degrees C, but
      did not produce a protein product. Antisense and ribozyme RNA binding depended
      upon the presence of intact ribosomes, was specific since, plasmid DNA did not
      associate with either ribosomes or polyribosomes, and was temperature dependent.
      Ribozyme-specific mRNA cleavage in the coupled system was inferred from
      translation inhibition studies and was confirmed by primer extension analysis.
      Thus, ribozyme RNA can inhibit target protein production in the coupled
      transcription translation system by competing out cellular mRNAs and via targeted
      message degradation.

PMID- 9020053
TI  - Binding constants in the formation of mammalian protein synthesis initiation
      complexes and the role of mRNA.
AB  - The findings of Parkhurst et al. (Biochemistry 33, 15168-15177:1994) that a 10
      mer oligoribonucleotide containing the AUG triplet enhances the binding of the
      eIF-2 x Met-tRNAi complex to the 40S ribosomal subunit are questioned on the
      basis of a re-evaluation of their calculations. It is not possible to conclude,
      as they did, that addition of the AUG-containing oligonucleotide produces an
      exceptionally large increase (as judged by the magnitude of the coupling free
      energy) in the binding of the eIF-2 x Met-tRNAi complex to the 40S subunit, or
      that their results are more consistent with internal initiation than with the
      scanning initiation model.

PMID- 9020054
TI  - The formate dehydrogenase isolated from the aerobe Methylobacterium sp. RXM is a
      molybdenum-containing protein.
AB  - The formate dehydrogenase (FDH) isolated from cells of Methylobacterium sp. RXM
      grown on molybdenum-containing mineral medium using methanol as carbon source,
      was partially purified (at least 90% pure as revealed by SDS-PAGE). The enzyme is
      unstable under oxygen and all the purification steps were conducted under strict
      anaerobic conditions. The molecular mass is 75 kDa (gel exclusion 300 kDa). The
      enzyme was characterized in terms of the kinetic parameters towards different
      substrates and electron acceptors, pH and temperature dependence and the effect
      of a wide range of compounds in the enzymatic activity. The EPR spectra of the
      dithionite reduced sample show, at low temperature (below 20 K), two rhombic EPR
      signals due to two distinct [Fe-S] centres (centre I at g-values 2.023, 1.951 and
      1.933, and centre II at g-values 2.054 and 1.913). At high temperature (around
      100 K) another rhombic EPR signal is optimally observed at g-values 2.002, 1.987
      and 1.959 and attributed to the molybdenum site. The EPR signals assigned to the
      iron-sulfur centres show a strong analogy with the aldehyde oxido-reductase from
      Desulfovibrio gigas known to contain a Mo-pterin and two [2Fe-2S] centres and
      whose crystallographic structure was recently resolved.

PMID- 9020055
TI  - Identification of a mouse homolog for the human hereditary haemochromatosis
      candidate gene.
AB  - Recently, a novel human major histocompatibility complex (MHC) class I-like gene
      (HLA-H) was reported as a candidate gene for human hereditary haemochromatosis, a
      recessive disease of iron metabolism with a remarkably high incidence in northern
      Europeans. Independently we have isolated this gene in the course of a search for
      new human MHC class I-related genes and named it MR2. Here we report a mouse
      homolog of this human gene. The mouse MR2 gene is similar to the human
      counterpart with an overall predicted amino acid sequence similarity of
      approximately 66% and it is expressed in various tissues as in human. The extra
      eight amino acid residues between the alpha1 and the alpha2 domains in the mouse
      molecule compared to the human counterpart can be explained by the creation of
      the coding sequence from the intron. While the human gene is located at the site
      telomeric to the MHC region on human chromosome 6, our study indicated the
      translocation of the mouse homolog from the site telomeric to the MHC on mouse
      chromosome 17 to chromosome 13 along with other genes. This mouse gene should be
      important in clarifying a possible role in iron metabolism.

PMID- 9020056
TI  - Interleukin-4 inhibits the gene expression and biosyntheis of cytosolic
      phospholipase A2 in lipopolysaccharide stimulated U937 macrophage cell line and
      freshly prepared adherent rheumatoid synovial cells.
AB  - We recently reported that interleukin-4 (IL-4) inhibited prostanoid synthesis
      through inhibiting cyclooxygenase 2 biosynthesis. In the present study, we
      examined the effect of IL-4 on the expression of cytosolic phospholipase A2
      (cPLA2). The amounts of protein and mRNA of cPLA2 were determined by western
      blotting and reverse transcription polymerase chain reaction (RT-PCR),
      respectively. Although interleukin-1alpha (IL-1alpha) and tumor necrosis factor
      alpha (TNFalpha) had little effect on the biosynthesis of cPLA2 in phorbol
      myristate acetate (PMA)-differentiated U937 cells, lipopolysaccharide (LPS)
      increased the protein level of cPLA2 in a dose-dependent manner. IL-4 inhibited
      the increased synthesis of cPLA2 at the mRNA level. In addition, IL-4 inhibited
      the biosynthesis of cPLA2 in untreated or LPS treated freshly prepared rheumatoid
      synovial cells at the mRNA level. These findings suggest that IL-4 inhibits
      prostanoid synthesis through inhibiting the expression of both cPLA2 and
      cyclooxygenase 2.

PMID- 9020058
TI  - Cyclin A is present in the endocytic compartment of rat liver cells and increases
      during liver regeneration.
AB  - Recent studies have implicated the cell cycle kinase cdc2 and cyclin A in the
      inhibition of the fusion of endocytic vesicles in vitro during mitosis. However,
      the presence of cyclins or their associated cyclin dependent kinases (cdks) in
      the endocytic fractions have not been reported. Using Western-blotting and
      immunocytochemistry approaches with different anticyclin A antibodies we have
      detected cyclin A in the endocytic compartment of the rat liver. During the pre
      replicative phase of liver regeneration the amount of cyclin A in endosomes
      increases significantly with a peak around 12 hours after partial hepatectomy.
      Cyclin A-dependent kinases, cdc2 and cdk2, were also found in isolated endosome
      fractions, showing a distinct kinetics of accumulation during the regenerative
      period. Finally, histone H1 kinase activity was detected associated with cyclin A
      in endocytic vesicles and increased in regenerating liver. These results suggest
      that changes in the organization and in the function of the endocytic compartment
      during the hepatocellular proliferation may be modulated by proteins involved in
      the regulation of the cell cycle.

PMID- 9020057
TI  - p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at
      the post-transcriptional level.
AB  - The cytokine tumor necrosis factor (TNF) alpha was found to stimulate the p38
      mitogen activated protein (MAP) kinase signalling cascade in human umbilical vein
      endothelial cells. TNFalpha increased the activity of the p38 substrate MAP
      kinase-activated-protein (MAPKAP) kinase 2 and the subsequent phosphorylation of
      the small heat shock protein Hsp27 about two to three fold. This stimulation was
      blocked almost completely by the specific p38 MAP kinase inhibitor SB203580. This
      inhibitor also suppressed the TNFalpha-induced surface expression of the
      endothelial adhesion molecule vascular cell adhesion molecule (VCAM)-1. In
      contrast, inhibition of p38 MAP kinase had no effect on the stimulated surface
      expression of the intercellular cell adhesion molecule (ICAM)-1. VCAM-1 mRNA
      accumulation induced by TNFalpha was not affected by SB203580, suggesting that
      the p38 MAP kinase signalling cascade regulates the endothelial expression of
      VCAM-1 at the post-transcriptional level.

PMID- 9020059
TI  - Quantification of peroxynitrite, superoxide, and peroxyl radicals by a new spin
      trap hydroxylamine 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine.
AB  - The reactions of hydroxylamine 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine
      hydrochloride (TEMPONE-H) with peroxynitrite, superoxide and peroxyl radicals
      were studied. It was shown that under these reactions TEMPONE-H is oxidized into
      a stable nitroxide 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidi-noxyl (TEMPONE).
      The reactivity of TEMPONE-H towards reactive oxygen species was compared with the
      spin traps DMPO and TMIO as well as with DMSO and SOD. The rate constants of
      reactions of TEMPONE-H with peroxynitrite and superoxide radicals were 6 x 10(9)
      M(-1)s(-1) and 1.2x10(4) M(-1)s(-1), respectively. Using TEMPONE-H the
      sensitivity in the detection of peroxynitrite or superoxide radical was about 10
      fold higher than using the spin traps DMPO or TMIO. Thus, TEMPONE-H may be used
      as a spin trap in chemical and biological systems to quantify peroxynitrite and
      superoxide radical formation.

PMID- 9020060
TI  - Rapid loss in the mitochondrial membrane potential during geranylgeranoic acid
      induced apoptosis.
AB  - A synthetic geranylgeranoic acid (GGA) induced apoptotic cell death in a human
      hepatoma cell line, HuH-7, but not in mouse primary cultured hepatocytes. Prior
      to chromatin condensation, GGA induced a dramatic loss of the mitochondrial
      membrane potential in 1 hour and in a dose dependent manner in HuH-7 cells, but
      not in the primary hepatocytes. Pretreatment with synthetic tetrapeptide cysteine
      protease inhibitor, either acetyl-Tyr-Val-Ala-Asp-chloromethylketone or acetyl
      Asp-Glu-Val-Asp-aldehyde, blocked GGA-induced apoptosis without preventing a
      rapid loss of the mitochondrial membrane potential. alpha-Tocopherol prevented
      the cells from GGA-induced apoptosis as well as from a rapid loss of the membrane
      potential. The present study strongly suggests that GGA induces apoptosis in
      hepatoma cells through derangement of mitochondrial function and subsequent
      activation of the cysteine protease cascade.

PMID- 9020061
TI  - Tissue distribution of SNAP-23 and its subcellular localization in 3T3-L1 cells.
AB  - The SNARE hypothesis of vesicular traffic proposes that three proteins,
      VAMP/synaptobrevin, syntaxin, and SNAP-25, constitute a complex that docks the
      vesicle at the target membrane. VAMP and syntaxin isoforms have been identified
      outside the nervous system, and a cDNA to a SNAP-25 related protein, SNAP-23, was
      recently identified in human lymphocytes. Here we report the generation of
      isoform-specific antibodies to SNAP-23 cloned from human melanoma cells, and
      their use in detecting the expression and localization of the endogenous SNAP-23
      protein in several tissues and cell lines. SNAP-23 was readily detected in liver,
      lung, kidney, and spleen, to a lesser extent in muscle and heart, and was almost
      undetectable in brain. The protein was also abundant in fibroblast, muscle, and
      fat cell lines, but relatively less enriched in neuroendocrine PC12 cells. SNAP
      23 abundance did not change during differentiation of 3T3-L1 fibroblasts into
      adipocytes. In both, SNAP-23 was membrane-bound and below detectable levels in
      the cytosolic fraction. Subcellular fractionation of 3T3-L1 adipocytes revealed
      that the majority of the protein was associated with plasma membranes. These
      findings support the conclusion that a tripartite SNARE complex exists outside of
      the nervous system, and suggest that SNAP-23 may play a role in vesicle traffic
      in most cell types.

PMID- 9020062
TI  - Discovery of a novel human G protein-coupled receptor gene (GPR25) located on
      chromosome 1.
AB  - We amplified human genomic DNA by the polymerase chain reaction (PCR) using
      oligonucleotides based on the primary sequence of the genes encoding the
      somatostatin receptors (SSTR) and the somatostatin-like receptor gene SLC-1. One
      resultant DNA fragment was used to screen a genomic DNA library resulting in the
      isolation of a gene, GPR25, encoding an additional member of the G protein
      coupled receptor family (GPCR). GPR25 is intronless throughout its open reading
      frame (ORF) and encodes a protein of 360 amino acids. The receptor encoded by
      GPR25 shares highest identity to the receptor encoded by GPR15, angiotensin II
      type 1A receptor, and somatostatin receptor 5. Northern analysis found no
      transcripts expressed in liver or any of the 12 brain regions analyzed.
      Fluorescence in situ hybridization analysis localized GPR25 to chromosome 1q32.1.

PMID- 9020063
TI  - Genomic structure and promoter characterization of the human ACTH receptor gene.
AB  - One kb of the 5'-flanking region of the human ACTH receptor gene was isolated and
      partially characterized. Transient transfections with hGH reporter confirmed the
      promoter activity in Y1 cells. Putative elements for transcription factors
      involved in regulation were noted in the sequence. The promoter activity of some
      of the constructs is responsive to a treatment by forskolin, due to the presence
      of several CRE-like sequences.

PMID- 9020064
TI  - A flavin reductase stimulates DszA and DszC proteins of Rhodococcus erythropolis
      IGTS8 in vitro.
AB  - Rhodococcus erythropolis IGTS8 is a gram positive bacterium, which can catabolize
      dibenzothiophene to 2-hydroxybiphenyl and inorganic sulfur without the cleavage
      of carbon-carbon bonds. Three structural genes, dszA, dszB, and dszC, have been
      cloned and shown to be necessary for this phenotype. Here, we demonstrate that a
      FMN:NADPH oxidoreductase from Vibrio harveyi complements activities of purified
      DszA and DszC proteins. Furthermore, we propose that DszA and DszC are oxygenase
      units that do not use NAD(P)H directly, but instead use FMNH2 from a FMN:NADPH
      oxidoreductase for oxygenation.

PMID- 9020065
TI  - Myosin subfragment-1 is fully equipped with factors essential for motor function.
AB  - The sliding velocity of actin filaments propelled by chicken skeletal myosin
      subfragment-1 (S1) was measured when the tail end of S1 was specifically bound to
      the glass surface. To achieve the specific binding, a regulatory light chain was
      replaced by a recombinant fusion protein of biotin-dependent transcarboxylase
      (BDTC) and chicken gizzard smooth muscle regulatory light chain (cgmRLC). The
      BDTC-cgmRLC of S1 was then attached to the glass surface using a biotin-avidin
      system. The velocity of actin filaments caused by S1 bound to the surface in this
      manner was 6.8 +/- 0.6 microm/sec at 29 degrees C, which was 3.5-fold greater
      than that (1.9 +/- 0.3 microm/sec) when bound directly to the surface as in
      previous studies, but similar to that caused by native chicken skeletal myosin
      (6.5 +/- 0.6 microm/sec). The actin-activated Mg-ATPase activity was similar to
      that of S1 before the RLC of S1 was exchanged for BDTC-cgmRLC. The results
      indicate that S1 can produce a normal fast movement of actin filaments as well as
      hydrolyse ATP and generate force.

PMID- 9020066
TI  - Expression of Src-like adapter protein mRNA is induced by all-trans retinoic
      acid.
AB  - By using a differential display method, specific bands were selected from ladder
      PCR products derived from ATRA-dependent differentiated U937 cells, in comparison
      with those of untreated U937. By screening the cDNA library of ATRA-dependent
      differentiated U937 cells with one of the PCR products, we cloned the src-like
      adapter protein (SLAP). Northern blot analysis of U937 cells with or without ATRA
      treatment indicated that the SLAP mRNA was clearly induced by ATRA. The induction
      was inhibited by the addition of cycloheximide, indicating that ATRA acted
      indirectly through synthesis of other proteins. The SLAP mRNA was induced in HL60
      and NB-4 but not in K562 or THP-1. Interestingly, these cells in which SLAP mRNA
      was induced by ATRA all showed ATRA-dependent cell differentiation. The
      relationship between SLAP and cell differentiation is unclear, but SLAP may
      transduce a signal for cell differentiation.

PMID- 9020067
TI  - Loss of expression of the p16 gene is frequent in malignant skin tumors.
AB  - Expression of the p16 gene from 30 malignant skin tumors has been surveyed by
      immunohistochemical assay. Gene point mutations were detected by DNA direct
      sequencing and the mRNA level of gene expression was measured by RT-PCR. A silent
      point mutation of the p16 gene was found in only one patient. However, loss of
      expression of the p16 gene was noticed in 23 of 29 samples (79.3%). Correlation
      between loss of expression of the p16 gene and metastasis is significant (p =
      0.0036). These findings suggest that loss of expression of the p16 gene may play
      a critical role in tumor progression of malignant skin tumors.

PMID- 9020069
TI  - Cloning and expression of cDNA encoding the human 150 kDa oxygen-regulated
      protein, ORP150.
AB  - We have cloned a cDNA encoding the human 150 kDa oxygen-regulated protein
      (ORP150) from hypoxia-treated astrocytoma U373 cDNA library. The deduced amino
      acid sequence of 999 residues contains a signal peptide and an ER retention-like
      signal at the N- and C-termini, respectively. It has a striking sequence
      similarity (91% identity) with Chinese hamster 170 kDa glucose-regulated protein
      (GRP170). The N-terminal half of ORP150 exhibits significant similarity to the
      ATPase domain of HSP70 family proteins with well-conserved ATP binding motifs.
      Northern blot analysis revealed that induction of ORP150 in U373 cells was not
      limited to hypoxia but also observed by 2-deoxyglucose or tunicamycin treatment.
      Furthermore, tissue specificity of expression of ORP150 was quite similar to that
      of GRP78. These findings suggest that ORP150 participates in quality control of
      proteins in the ER in response to diverse environmental stresses.

PMID- 9020068
TI  - Fas-signaling and effects on receptor tyrosine kinase signal transduction in
      human breast epithelial cells.
AB  - Fas-mediated cell death was examined in MCF-10AT preneoplastic human breast
      epithelial cells. Treatment with anti-Fas for 48 h induced apoptosis with cells
      exhibiting typical apoptotic features including loss of cell contact,
      condensation of chromatin, and increased staining of the nuclear membrane. DNA
      fragmentation occurred in response to anti-Fas treatment. Anti-Fas treatment
      resulted in decreased p53 protein levels, while bcl-2 and bax protein levels
      remained unaffected. Cells treated with anti-Fas also exhibited increased
      tyrosine phosphorylation of the c-met growth factor receptor tyrosine kinase.
      Immunoprecipitation experiments demonstrated that Fas associated with c-erbB2 and
      c-met in untreated cells. Treatment with anti-Fas, however, significantly
      decreased Fas-c-erbB2 and Fas-c-met association. Anti-Fas treatment of these
      cells caused a significant decrease in p120-GAP levels, ERK-1 levels, and
      phosphorylation, as well as Grb2-Sosl and MEK-1-ERK-1 association. These results
      show that Fas-signaling exerted a suppressive effect on p53 levels and on
      downstream effectors of receptor tyrosine kinase signal transduction, thereby
      ensuring cell death.

PMID- 9020070
TI  - Chemical selection for catalysis in combinatorial antibody libraries.
AB  - For the past decade the immune system has been exploited as a rich source of de
      novo catalysts. Catalytic antibodies have been shown to have chemoselectivity,
      enantioselectivity, large rate accelerations, and even an ability to reroute
      chemical reactions. In many instances catalysts have been made for reactions for
      which there are no known natural or man-made enzymes. Yet, the full power of this
      combinatorial system can only be exploited if there was a system that allows for
      the direct selection of a particular function. A method that allows for the
      direct chemical selection for catalysis from antibody libraries was so devised,
      whereby the positive aspects of hybridoma technology were preserved and re
      formatted in the filamentous phage system to allow direct selection of catalysis.
      This methodology is based on a purely chemical selection process, making it more
      general than biologically based selection systems because it is not limited to
      reaction products that perturb cellular machinery.

PMID- 9020072
TI  - Enantiomeric excesses in meteoritic amino acids.
AB  - Gas chromatographic-mass spectral analyses of the four stereoisomers of 2-amino
      2,3-dimethylpentanoic acid (dl-alpha-methylisoleucine and dl-alpha
      methylalloisoleucine) obtained from the Murchison meteorite show that the L
      enantiomer occurs in excess (7.0 and 9.1%, respectively) in both of the
      enantiomeric pairs. Similar results were obtained for two other alpha-methyl
      amino acids, isovaline and alpha-methylnorvaline, although the alpha hydrogen
      analogs of these amino acids, alpha-amino-n-butyric acid and norvaline, were
      found to be racemates. With the exception of alpha-amino-n-butyric acid, these
      amino acids are either unknown or of limited occurrence in the biosphere. Because
      carbonaceous chondrites formed 4.5 billion years ago, the results are indicative
      of an asymmetric influence on organic chemical evolution before the origin of
      life.

PMID- 9020073
TI  - Atomistic Simulation of Shock Wave-Induced Melting in Argon
AB  - A three-dimensional molecular dynamics simulation of shock wave loading was
      undertaken to investigate the Hugoniot equation of state at the transition of
      argon from solid to liquid. The simulated data agree with shock wave and static
      high-pressure experimental data. The melting transition in this simulation occurs
      without overshooting the argon melting temperature. There are two discontinuities
      that may bracket a mixed-phase region of solid and liquid along the simulated
      argon Hugoniot. This is an intrinsic feature of the Hugoniot crossing the argon
      melting curve and does not require the addition of any solid-solid phase
      transition.

PMID- 9020071
TI  - A functional model related to cytochrome c oxidase and its electrocatalytic four
      electron reduction of O2.
AB  - A cytochrome c oxidase model that consists of a cobalt(II) porphyrin with a
      copper(I) triazacyclononane macrocycle fastened on the distal face and an
      imidazole covalently attached to the proximal face has been synthesized and
      characterized. Redox titrations with molecular oxygen (O2) and cobaltocene were
      carried out, and O2 was found to bind irreversibly in a 1:1 ratio to the model
      compound. This O2 adduct (a bridged peroxide) can be fully reduced to the
      deoxygenated form with four equivalents of cobaltocene. The model compound was
      adsorbed on an edge-plane graphite electrode, and rotating ring-disk voltammetry
      was used to monitor the electrocatalytic reduction of O2. Four-electron reduction
      of O2 was observed at physiological pH.

PMID- 9020074
TI  - Twentieth-Century Sea Surface Temperature Trends
AB  - An analysis of historical sea surface temperatures provides evidence for global
      warming since 1900, in line with land-based analyses of global temperature
      trends, and also shows that over the same period, the eastern equatorial Pacific
      cooled and the zonal sea surface temperature gradient strengthened. Recent
      theoretical studies have predicted such a pattern as a response of the coupled
      ocean-atmosphere system to an exogenous heating of the tropical atmosphere. This
      pattern, however, is not reproduced by the complex ocean-atmosphere circulation
      models currently used to simulate the climatic response to increased greenhouse
      gases. Its presence is likely to lessen the mean 20th-century global temperature
      change in model simulations.

PMID- 9020075
TI  - Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's
      thyroiditis.
AB  - The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis
      (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune
      thyroids, expressed Fas. Interleukin-1beta (IL-1beta), abundantly produced in HT
      glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas
      resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to
      be constitutively expressed both in normal and HT thyrocytes and was able to kill
      Fas-sensitive targets. Exposure to IL-1beta induced thyrocyte apoptosis, which
      was prevented by antibodies that block Fas, suggesting that IL-1beta-induced Fas
      expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL
      interactions among HT thyrocytes may contribute to clinical hypothyroidism.

PMID- 9020076
TI  - Isolation of putative progenitor endothelial cells for angiogenesis.
AB  - Putative endothelial cell (EC) progenitors or angioblasts were isolated from
      human peripheral blood by magnetic bead selection on the basis of cell surface
      antigen expression. In vitro, these cells differentiated into ECs. In animal
      models of ischemia, heterologous, homologous, and autologous EC progenitors
      incorporated into sites of active angiogenesis. These findings suggest that EC
      progenitors may be useful for augmenting collateral vessel growth to ischemic
      tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic
      agents, respectively, to sites of pathologic or utilitarian angiogenesis.

PMID- 9020077
TI  - Somatic frameshift mutations in the BAX gene in colon cancers of the
      microsatellite mutator phenotype.
AB  - Cancers of the microsatellite mutator phenotype (MMP) show exaggerated genomic
      instability at simple repeat sequences. More than 50 percent (21 out of 41) of
      human MMP+ colon adenocarcinomas examined were found to have frameshift mutations
      in a tract of eight deoxyguanosines [(G)8] within BAX, a gene that promotes
      apoptosis. These mutations were absent in MMP- tumors and were significantly less
      frequent in (G)8 repeats from other genes. Frameshift mutations were present in
      both BAX alleles in some MMP+ colon tumor cell lines and in primary tumors. These
      results suggest that inactivating BAX mutations are selected for during the
      progression of colorectal MMP+ tumors and that the wild-type BAX gene plays a
      suppressor role in a p53-independent pathway for colorectal carcinogenesis.

PMID- 9020078
TI  - Involvement of pre- and postsynaptic mechanisms in posttetanic potentiation at
      Aplysia synapses.
AB  - Posttetanic potentiation (PTP) is a common form of short-term synaptic plasticity
      that is generally thought to be entirely presynaptic. Consistent with that idea,
      PTP of evoked excitatory postsynaptic potentials at Aplysia sensory-motor neuron
      synapses in cell culture was reduced by presynaptic injection of a slow calcium
      chelator and was accompanied by an increase in the frequency but not the
      amplitude of spontaneous excitatory postsynaptic potentials. However, PTP was
      also reduced by postsynaptic injection of a rapid calcium chelator or
      postsynaptic hyperpolarization. Thus, PTP at these synapses is likely to involve
      a postsynaptic induction mechanism in addition to the known presynaptic
      mechanisms.

PMID- 9020079
TI  - A mammalian telomerase-associated protein.
AB  - The telomerase ribonucleoprotein catalyzes the addition of new telomeres onto
      chromosome ends. A gene encoding a mammalian telomerase homolog called TP1
      (telomerase-associated protein 1) was identified and cloned. TP1 exhibited
      extensive amino acid similarity to the Tetrahymena telomerase protein p80 and was
      shown to interact specifically with mammalian telomerase RNA. Antiserum to TP1
      immunoprecipitated telomerase activity from cell extracts, suggesting that TP1 is
      associated with telomerase in vivo. The identification of TP1 suggests that
      telomerase-associated proteins are conserved from ciliates to humans.

PMID- 9020080
TI  - Immunoglobulin E production in the absence of interleukin-4-secreting CD1
      dependent cells.
AB  - A lymphocyte population that expresses surface markers found on T cells and
      natural killer (NK) cells secretes large amounts of interleukin-4 (IL-4)
      immediately after T cell receptor ligation. These NK-like T cells are thus
      thought to be important for the initiation of type 2 T helper cell (TH2)
      responses. CD1-deficient mice were found to lack this lymphocyte subset, but they
      could nevertheless mount a protypical TH2 response; after immunization with
      antibody to immunoglobulin D (IgD), CD1-deficient mice produced IgE. Thus,
      although dependent on CD1 for their development, IL-4-secreting NK-like T cells
      are not required for TH2 responses.

PMID- 9020081
TI  - Structural and functional conservation of the Caenorhabditis elegans timing gene
      clk-1.
AB  - Mutations in the Caenorhabditis elegans gene clk-1 affect biological timing and
      extend longevity. The gene clk-1 was identified, and the cloned gene complemented
      the clk-1 phenotypes and restored normal longevity. The CLK-1 protein was found
      to be conserved among eukaryotes, including humans, and structurally similar to
      the yeast metabolic regulator Cat5p (also called Coq7p). These proteins contain a
      tandem duplication of a core 82-residue domain. clk-1 complemented the phenotype
      of cat5/coq7 null mutants, demonstrating that clk-1 and CAT5/COQ7 share
      biochemical function and that clk-1 acts at the level of cellular physiology.

PMID- 9020082
TI  - Structure of Bcl-xL-Bak peptide complex: recognition between regulators of
      apoptosis.
AB  - Heterodimerization between members of the Bcl-2 family of proteins is a key event
      in the regulation of programmed cell death. The molecular basis for heterodimer
      formation was investigated by determination of the solution structure of a
      complex between the survival protein Bcl-xL and the death-promoting region of the
      Bcl-2-related protein Bak. The structure and binding affinities of mutant Bak
      peptides indicate that the Bak peptide adopts an amphipathic alpha helix that
      interacts with Bcl-xL through hydrophobic and electrostatic interactions.
      Mutations in full-length Bak that disrupt either type of interaction inhibit the
      ability of Bak to heterodimerize with Bcl-xL.

PMID- 9020083
TI  - A protein-counting mechanism for telomere length regulation in yeast.
AB  - In the yeast Saccharomyces cerevisiae, telomere elongation is negatively
      regulated by the telomere repeat-binding protein Rap1p, such that a narrow length
      distribution of telomere repeat tracts is observed. This length regulation was
      shown to function independently of the orientation of the telomere repeats. The
      number of repeats at an individual telomere was reduced when hybrid proteins
      containing the Rap1p carboxyl terminus were targeted there by a heterologous DNA
      binding domain. The extent of this telomere tract shortening was proportional to
      the number of targeted molecules, consistent with a feedback mechanism of
      telomere length regulation that can discriminate the precise number of Rap1p
      molecules bound to the chromosome end.

PMID- 9020084
TI  - Defective transcription-coupled repair of oxidative base damage in Cockayne
      syndrome patients from XP group G.
AB  - In normal human cells, damage due to ultraviolet light is preferentially removed
      from active genes by nucleotide excision repair (NER) in a transcription-coupled
      repair (TCR) process that requires the gene products defective in Cockayne
      syndrome (CS). Oxidative damage, including thymine glycols, is shown to be
      removed by TCR in cells from normal individuals and from xeroderma pigmentosum
      (XP)-A, XP-F, and XP-G patients who have NER defects but not from XP-G patients
      who have severe CS. Thus, TCR of oxidative damage requires an XPG function
      distinct from its NER endonuclease activity. These results raise the possibility
      that defective TCR of oxidative damage contributes to the developmental defects
      associated with CS.

PMID- 9020085
TI  - Regulation of replicon size in Xenopus egg extracts.
AB  - Once a specific number of cells have been produced in the early Xenopus laevis
      embryo, replicon size during the S phase of the cell cycle increases. Here, it is
      reported that similar increase in replicon size occurred when the concentration
      of nuclei in replication-competent Xenopus egg extracts exceeded a critical
      threshold. In this system, the origin recognition complex (ORC) did not become
      stoichiometrically limiting for initiation, and similar amounts of this complex
      bound to chromatin regardless of replicon size. These data suggest that in early
      development, an unidentified factor controls how many preformed ORC-DNA complexes
      initiate DNA replication.

PMID- 9020086
TI  - Isolation and characterization of a GDP/GTP exchange protein specific for the
      Rab3 subfamily small G proteins.
AB  - The Rab small G protein family, consisting of nearly 30 members, is implicated in
      intracellular vesicle trafficking. They cycle between the GDP-bound inactive and
      GTP-bound active forms, and the former is converted to the latter by the action
      of a GDP/GTP exchange protein (GEP). No GEP specific for each Rab family member
      or Rab subfamily has been isolated. Here we purified a GEP from rat brain with
      lipid-modified Rab3A as a substrate. The purified protein was specifically active
      on Rab3A, Rab3C, and Rab3D of the Rab3 subfamily. Of these subfamily members,
      Rab3A and Rab3C are implicated in Ca2+-dependent exocytosis, particularly in
      neurotransmitter release. This GEP (Rab3 GEP) was active on the lipid-modified
      form, but not on the lipid-unmodified form. Rab3 GEP showed a minimum molecular
      mass of about 200 kDa on SDS-polyacrylamide gel electrophoresis. We cloned its
      cDNA from a rat brain cDNA library and determined its primary structure. The
      isolated cDNA encoded a protein with a Mr of 177,982 and 1,602 amino acids, which
      showed no homology to any known protein. The recombinant protein exhibited GEP
      activity toward Rab3A, Rab3C, and Rab3D. Northern blot and Western blot analyses
      indicated that Rab3 GEP was expressed in all the rat tissues examined with the
      highest expression in brain.

PMID- 9020087
TI  - Lysine 129 of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) participates
      in the binding of ATP to inhibit the cyclic ADP-ribose hydrolase.
AB  - CD38 catalyzes not only the formation of cyclic ADP-ribose (cADPR) from NAD+ but
      also the hydrolysis of cADPR to ADP-ribose (ADPR), and ATP inhibits the
      hydrolysis (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto,
      T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). In the
      present study, using purified recombinant CD38, we showed that the cADPR
      hydrolase activity of CD38 was inhibited by ATP in a competitive manner with
      cADPR. To identify the binding site for ATP and/or cADPR, we labeled the purified
      CD38 with FSBA. Sequence analysis of the lysylendopeptidase-digested fragment of
      the labeled CD38 indicated that the FSBA-labeled residue was Lys-129. We
      introduced site-directed mutations to change the Lys-129 of CD38 to Ala and to
      Arg. Neither mutant was labeled with FSBA nor catalyzed the hydrolysis of cADPR
      to ADPR. Furthermore, the mutants did not bind cADPR, whereas they still used
      NAD+ as a substrate to form cADPR and ADPR. These results indicate that Lys-129
      of CD38 participates in cADPR binding and that ATP competes with cADPR for the
      binding site, resulting in the inhibition of the cADPR hydrolase activity of
      CD38.

PMID- 9020088
TI  - The Dictyostelium mitogen-activated protein kinase ERK2 is regulated by Ras and
      cAMP-dependent protein kinase (PKA) and mediates PKA function.
AB  - The chemoattractant cAMP, acting through serpentine cAMP receptors, results in a
      rapid and transient stimulation of the Dictyostelium mitogen-activated protein
      kinase ERK2 activity (). In this study we show that other pathways required for
      aggregation, including Ras and cAMP-dependent protein kinase (PKA), are important
      regulators of ERK2 activation and adaptation. By examining both the level and
      kinetics of activation and adaptation of ERK2, we show that Ras is a negative
      regulator of ERK2. Activated Ras or disruption of a Ras GAP gene results in
      reduced ERK2 activation whereas disruption of putative Ras GEF or expression of
      dominant negative Ras proteins have a more rapid, higher, and extended
      activation. CRAC, a PH domain-containing protein required for adenylyl cyclase
      activation, is also required for proper ERK2 adaptation. PKA overexpression
      results in a more rapid, higher level of activation, whereas pka null cells show
      a lower level but more extended ERK2 activation. Furthermore, we show that
      constitutive expression of PKA catalytic subunit bypasses the requirement of ERK2
      for aggregation and later development, indicating that PKA lies downstream from
      ERK2 and that ERK2 may regulate one or more components of the signaling pathway
      required for mediating PKA function, possibly by directly regulating PKA R or a
      protein controlling the intracellular level of cAMP.

PMID- 9020089
TI  - Mechanisms for solvent tolerance in bacteria.
AB  - The development of tolerance in Pseudomonas putida DOT-T1 to toluene and related
      highly toxic compounds involves short- and long-term responses. The short-term
      response is based on an increase in the rigidity of the cell membrane by rapid
      transformation of the fatty acid cis-9,10-methylene hexadecanoic acid
      (C17:cyclopropane) to unsaturated 9-cis-hexadecenoic acid (C16:1,9 cis) and
      subsequent transformation to the trans isomer. The long-term response involves in
      addition to the changes in fatty acids, alterations in the level of the
      phospholipid polar head groups: cardiolipin increases and
      phosphatidylethanolamine decreases. The two alterations lead to increased cell
      membrane rigidity and should be regarded as physical mechanisms that prevent
      solvent penetrance. Biochemical mechanisms that decrease the concentration of
      toluene in the cell membrane also take place and involve: (i) a solvent exclusion
      system and (ii) metabolic removal of toluene via oxidation. Mutants unable to
      carry out cis --> trans isomerization of unsaturated lipids, that exhibit altered
      cell envelopes because of the lack of the OprL protein, or that are unable to
      exclude toluene from cell membranes are hypersensitive to toluene.

PMID- 9020091
TI  - Interaction of the GTP-binding and GTPase-activating domains of ARD1 involves the
      effector region of the ADP-ribosylation factor domain.
AB  - ADP-ribosylation factors (ARFs) are a family of approximately 20-kDa guanine
      nucleotide-binding proteins and members of the Ras superfamily, originally
      identified and purified by their ability to enhance the ADP-ribosyltransferase
      activity of cholera toxin and more recently recognized as critical participants
      in vesicular trafficking pathways and phospholipase D activation. ARD1 is a 64
      kDa protein with an 18-kDa carboxyl-terminal ARF domain (p3) and a 46-kDa amino
      terminal extension (p5) that is widely expressed in mammalian tissues. Using
      recombinant proteins, we showed that p5, the amino-terminal domain of ARD1,
      stimulates the GTPase activity of p3, the ARF domain, and appears to be the
      GTPase-activating protein (GAP) component of this bifunctional protein, whereas
      in other members of the Ras superfamily a separate GAP molecule interacts with
      the effector region of the GTP-binding protein. p5 stimulated the GTPase activity
      of p3 but not of ARF1, which differs from p3 in several amino acids in the
      effector domain. After substitution of 7 amino acids from p3 in the appropriate
      position in ARF1, the chimeric protein ARF1(39-45p3) bound to p5, which increased
      its GTPase activity. Specifically, after Gly40 and Thr45 in the putative effector
      domain of ARF1 were replaced with the equivalent Asp and Pro, respectively, from
      p3, functional interaction of the chimeric ARF1 with p5 was increased. Thus,
      Asp25 and Pro30 of the ARF domain (p3) of ARD1 are involved in its functional and
      physical interaction with the GTPase-activating (p5) domain of ARD1. After
      deletion of the amino-terminal 15 amino acids from ARF1(39-45p3), its interaction
      with p5 was essentially equivalent to that of p3, suggesting that the amino
      terminus of ARF1(39-45p3) may interfere with binding to p5. These results are
      consistent with the conclusion that the GAP domain of ARD1 interacts with the
      effector region of the ARF domain and thereby stimulates GTP hydrolysis.

PMID- 9020090
TI  - Histidine 265 is important for covalent catalysis by vaccinia topoisomerase and
      is conserved in all eukaryotic type I enzymes.
AB  - Vaccinia topoisomerase catalyzes DNA cleavage and rejoining via
      transesterification to pentapyrimidine recognition site 5'-(C/T)CCTT downward
      arrow in duplex DNA. The proposed reaction mechanism involves general-base
      catalysis of the attack by active site nucleophile Tyr-274 on the scissile
      phosphodiester and general-acid catalysis of the expulsion of the 5'-deoxyribose
      oxygen on the leaving DNA strand. The pKa values suggest histidine and cysteine
      side chains as candidates for the roles of proton acceptor and donor,
      respectively. To test this, we replaced each of the eight histidines and two
      cysteines of the vaccinia topoisomerase with alanine. Single mutants C100A and
      C211A and a double mutant C100A-C211A were fully active in DNA relaxation,
      indicating that a cysteine is not the general acid. Only one histidine mutation,
      H265A, affected enzyme activity. The rates of DNA relaxation, single-turnover
      strand cleavage, and single-turnover religation by H265A were 2 orders of
      magnitude lower than the wild-type rates. Yet the H265A mutation did not alter
      the dependence of the cleavage rate on pH, indicating that His-265 is not the
      general base. Replacing His-265 with glutamine or asparagine slowed DNA
      relaxation and single-turnover cleavage to about one-third of the wild-type rate.
      All three mutations, H265A, H265N, and H265Q, skewed the cleavage-religation
      equilibrium in favor of the covalently bound state. His-265 is strictly conserved
      in every member of the eukaryotic type I topoisomerase family.

PMID- 9020092
TI  - Inhibitory mechanism of serpins. Mobility of the C-terminal region of the
      reactive-site loop.
AB  - The reactive-site loops of serpins are characterized by a defined mobility where
      the loop adopts a new secondary structure as an essential part of the inhibitory
      process. While the importance of mobility in the N-terminal region of the
      reactive-site loop has been well studied, the role of mobility in the C-terminal
      portion has not been investigated. The requirements for mobility of the C
      terminal portion of the reactive-site loop of alpha1-antitrypsin were
      investigated by creating a disulfide bridge between the P'3 residue and residue
      283 near the top of strand 2C; this disulfide would restrict the mobility of the
      C-terminal portion of the reactive-site loop by locking together strands 1 and 2
      of the C beta-sheet. The engineered disulfide bond had no effect on the
      inhibitory activity of alpha1-antitrypsin, indicating that there is no
      requirement for mobility in this region of the molecule. Moreover, these results,
      coupled with those from molecular modeling, indicate that insertion into the A
      beta-sheet of the intact reactive-loop beyond P12 is not rate-limiting for the
      formation of the stable complex. The engineered disulfide bond should also prove
      useful in the creation of more stable serpin variants; for example, such a bond
      in plasminogen activator inhibitor-1 would prevent it from becoming latent by
      locking strand 1C onto the C beta-sheet.

PMID- 9020093
TI  - Antisense inhibition of silica-induced tumor necrosis factor in alveolar
      macrophages.
AB  - Tumor necrosis factor-alpha (TNFalpha) has been shown to play an important role
      in the pathogenesis of silicotic fibrosis. In this study, antisense
      oligonucleotides targeted to TNFalpha mRNA were used to inhibit silica-induced
      TNFalpha gene expression in alveolar macrophages. To achieve macrophage-specific
      oligonucleotide delivery, a molecular conjugate consisting of mannosylated
      polylysine that exploits endocytosis via the macrophage mannose receptor was
      used. Complexes were formed between the mannosylated polylysine and
      oligonucleotides and added to the cells in the presence of silica. Enzyme-linked
      immunoadsorbent assay showed that the complex consisting of the conjugate and
      antisense oligomer effectively inhibited TNFalpha production, whereas the
      oligomer alone had much less effect. Reverse transcriptase-polymerase chain
      reaction analysis revealed that the reduction in TNFalpha secretion was
      associated with specific ablation of targeted TNFalpha mRNA. The conjugate alone
      or conjugate complexed with inverted or sense sequence oligonucleotide had no
      effect. The promoting effect of the conjugate on antisense activity was shown to
      be due to enhanced cellular uptake of the oligomer via mannose receptor-mediated
      endocytosis. Cells lacking mannose receptors showed no susceptibility to the
      conjugate treatment. These results indicate that effective and selective
      inhibition of macrophage TNFalpha expression can be achieved using the antisense
      mannosylated polylysine system.

PMID- 9020094
TI  - Negative modulation of membrane localization of the Raf-1 protein kinase by
      hyperphosphorylation.
AB  - The serine/threonine-specific protein kinase Raf-1 plays a key role in mitogenic
      signal transduction by coupling Ras to the mitogen-activated protein (MAP) kinase
      cascade. Ras-mediated translocation to the plasma membrane represents a crucial
      step in the process of serum-stimulated Raf-1 kinase activation. The exact role
      of the multisite phosphorylation in Raf regulation, however, is not clear. We
      have previously reported that the mobility shift-associated hyperphosphorylation
      of Raf correlates with a reduction of serum-stimulated Raf kinase activity
      (Wartmann, M., and Davis, R. J. (1994) J. Biol. Chem. 269, 6695-6701). Here we
      show that incubation of serum-starved CHO cells with D609, a purported inhibitor
      of phosphatidylcholine-specific phospholipase C, also results in a mobility shift
      of Raf-1 that is due to hyperphosphorylation on sites identical to those observed
      following mitogen stimulation. Subcellular fractionation analyses revealed that
      D609-induced mobility shift-associated hyperphosphorylation was paralleled by a
      decreased membrane association of Raf-1. Similar results were obtained in an in
      vitro reconstitution system. Furthermore, PD98059, a specific inhibitor of
      activation of the MAP kinase kinase MEK, prevented D609-induced Raf
      hyperphosphorylation and restored the amount of membrane-bound Raf to control
      levels. Taken together, these data suggest that mobility shift-associated
      hyperphosphorylation of Raf-1, by virtue of reducing the amount of plasma
      membrane-bound Raf-1, represents a negative feedback mechanism contributing to
      the desensitization of the MAP kinase signaling cascade.

PMID- 9020095
TI  - Purification and characterization of two novel hypersensitive response-inducing
      specific elicitors produced by the cowpea rust fungus.
AB  - Two novel elicitor peptides that are produced by the race 1 of the cowpea rust
      fungus Uromyces vignae and that specifically induce a hypersensitive response (a
      putative form of programmed cell death) in a resistant cultivar of cowpea (Vigna
      unguiculata L. Walp) have been purified to homogeneity. Purification steps
      included gel filtration, anion-exchange chromatography, continuous elution
      electrophoresis, and reversed-phase C18 high performance liquid chromatography.
      The relative molecular masses of the peptide elicitors as deduced from Tricine
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 5600 Da (major)
      and 5800 Da (minor), respectively. Peptide 1 (major) and the minor copurifying
      peptide (peptide 2) resolved at the final C18 high performance liquid
      chromatography step. The NH2 terminus of peptide 1 was deblocked with anhydrous
      trifluoroacetic acid prior to sequencing. However, the NH2 terminus of peptide 2
      was free. The acidic and hydrophobic peptides show some homology between
      themselves but do not show any significant similarity with known proteins. The
      two specific elicitors may be products of two avirulence genes corresponding to
      the two genes for resistance in the resistant cultivar.

PMID- 9020096
TI  - Transcriptional regulation of the hepatocyte growth factor gene by the nuclear
      receptors chicken ovalbumin upstream promoter transcription factor and estrogen
      receptor.
AB  - Hepatocyte growth factor (HGF) is a multifunctional cytokine that controls the
      growth and differentiation of various tissues. Previously, we described the
      existence of a negative cis-acting regulatory element(s) within the -1- to -0.7
      kilobase pair (kb) portion of the 5'-flanking region of the mouse HGF promoter.
      In the present study, we show that the repressor element is located at position 
      872 to -860 base pairs and comprises an imperfect estrogen-responsive element 5'
      AGGTCAGAAAGACCA-3'. We demonstrate that chicken ovalbumin upstream promoter
      transcription factor (COUP-TF), a nuclear orphan receptor belonging to the
      steroid/thyroid hormone receptor superfamily, through binding to this site
      effectively silences the transcriptional activity of the HGF promoter. We show
      that estrogen receptor, on the other hand, relieves the repressive action of COUP
      TF, resulting in the induction of the HGF promoter. Using mice transgenic for
      either 2.7 or 0.7 kb of the HGF promoter region linked to the chloramphenicol
      acetyltransferase reporter gene, we found that injection of estradiol stimulates
      HGF promoter activity in tissues such as the mammary gland and ovary of mice
      harboring 2.7 but not 0.7 kb of the mouse HGF promoter region. Potential
      involvement of the CCAAT/enhancer-binding protein (C/EBP) family of transcription
      factors in the regulation of HGF gene expression is also discussed.

PMID- 9020097
TI  - Characterization of the low molecular weight photosystem II reaction center
      subunits and their light-induced modifications by mass spectrometry.
AB  - A sensitive and simple reverse phase HPLC purification scheme was developed for
      the rapid separation of the small protein subunits from photosystem II reaction
      center preparations. The precise molecular masses of the alpha- and beta-subunits
      of cytochrome b559 and the psbI gene product from pea plants, found to be 4394.6
      +/- 0. 6, 9283.6 +/- 0.7, and 4209.5 +/- 0.5 Da, respectively, were then
      successfully determined for the first time by electrospray- and fast atom
      bombardment-mass spectrometry. Discrepancies between the molecular weights
      assigned and those calculated from the respective DNA sequences were observed for
      alpha- and beta-subunits of cytochrome b559. Currently, the nucleotide sequence
      of the psbI gene product from pea plants is not available. Application of novel
      mapping and sequencing strategies has assured the elucidation of full primary
      structures of all of the purified subunits. The modifications identified here
      include the post-translational processing of the initiating methionine on both
      subunits of cytochrome b559, NH2-terminal acetylation and an mRNA editing site at
      residue 26 (Ser --> Phe) on the beta-subunit, and retention of the NH2-terminal
      formyl-Met on the psbI gene product. In addition, specific oxidation of a single
      amino acid residue was identified on the psbI gene product and the beta-subunit
      purified from light-treated reaction center preparations. Overall, these studies
      provide the first detailed primary structural characterization of the small
      subunits of the reaction center complex and their associated light-induced
      modifications.

PMID- 9020098
TI  - Differential prenyl pyrophosphate binding to mammalian protein
      geranylgeranyltransferase-I and protein farnesyltransferase and its consequence
      on the specificity of protein prenylation.
AB  - Protein geranylgeranyltransferase-I (PGGT-I) and protein farnesyltransferase
      (PFT) attach geranylgeranyl and farnesyl groups, respectively, to the C termini
      of eukaryotic cell proteins. In vitro, PGGT-I and PFT can transfer both
      geranylgeranyl and farnesyl groups from geranylgeranyl pyrophosphate (GGPP) and
      farnesyl pyrophosphate (FPP) to their protein or peptide prenyl acceptor
      substrates. In the present study it is shown that PGGT-I binds GGPP 330-fold
      tighter than FPP and that PFT binds FPP 15-fold tighter than GGPP. Therefore, in
      vivo, where both GGPP and FPP compete for the binding to prenyltransferases, PGGT
      I and PFT will likely be bound predominantly to GGPP and FPP, respectively.
      Previous studies have shown that K-Ras4B and the Ras-related GTPase TC21 are
      substrates for both PGGT-I and PFT in vitro. It is shown that TC21 can compete
      with the C-terminal peptide of the gamma subunit of heterotrimeric G proteins and
      with the C-terminal peptide of lamin B for geranylgeranylation by PGGT-I and for
      farnesylation by PFT, respectively. K-Ras4B competes in both cases but is almost
      exclusively farnesylated by PFT in the presence of the lamin B peptide
      competitor. Rapid and single turnover kinetic studies indicate that the rate
      constant for the PGGT-I-catalyzed geranylgeranyl transfer step of the reaction
      cycle is 14-fold larger than the steady-state turnover number, which indicates
      that the rate of the overall reaction is limited by a step subsequent to prenyl
      transfer such as release of products from the enzyme. PGGT-I-catalyzed
      farnesylation is 37-fold slower than geranylgeranylation and is limited by the
      farnesyl transfer step. These results together with earlier studies provide a
      paradigm for the substrate specificity of PGGT-I and PFT and provide information
      that is critical for the design of prenyltransferase inhibitors as anti-cancer
      agents.

PMID- 9020099
TI  - Evidence that cholesteryl ester transfer protein-mediated reductions in
      reconstituted high density lipoprotein size involve particle fusion.
AB  - It is well established that cholesteryl ester transfer protein (CETP) changes the
      size of high density lipoproteins (HDL) during incubation in vitro. It has been
      suggested that HDL.CETP.HDL ternary complex formation is involved in these
      changes. The present results, which are consistent with CETP changing the size of
      spherical reconstituted HDL (rHDL) by a mechanism involving fusion, support the
      ternary complex hypothesis. When rHDL containing a core of cholesteryl esters and
      either three molecules of apolipoprotein (apo) A-I/particle, (A-I)rHDL, or six
      molecules of apoA-II/particle, (A-II)rHDL, were incubated individually with CETP,
      their respective diameters decreased from 9.4 to 7.8 nm and from 9.8 to 8.8 nm.
      The small (A-I)rHDL and (A-II)rHDL contained, respectively, two molecules of apoA
      I/particle and four molecules of apoA-II/particle. As all of the rHDL lipids and
      apolipoproteins were quantitatively recovered at the end of the incubations, it
      was apparent that there was a 50% increase in the number of particles. This
      increase in the number of particles can be explained as follows: (i) sequential
      binding of two rHDL to CETP to generate a ternary complex, (ii) fusion of the
      rHDL in the ternary complex, and (iii) rearrangement of the fusion product into
      three small particles. Various spectroscopic techniques were used to show that
      the small rHDL were structurally distinct from the original rHDL. These results
      provide the first evidence that CETP mediates the fusion of spherical rHDL.

PMID- 9020100
TI  - Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane
      potential in a malarial parasite.
AB  - At present, approaches to studying mitochondrial functions in malarial parasites
      are quite limited because of the technical difficulties in isolating functional
      mitochondria in sufficient quantity and purity. We have developed a flow
      cytometric assay as an alternate means to study mitochondrial functions in intact
      erythrocytes infected with Plasmodium yoelii, a rodent malaria parasite. By using
      a very low concentration (2 nM) of a lipophilic cationic fluorescent probe,
      3,3'dihexyloxacarbocyanine iodide, we were able to measure mitochondrial membrane
      potential(DeltaPsim) in live intact parasitized erythrocytes through flow
      cytometry. The accumulation of the probe into parasite mitochondria was dependent
      on the presence of a membrane potential since inclusion of carbonyl cyanide m
      chlorophenylhydrazone, a protonophore, dissipated the membrane potential and
      abolished the probe accumulation. We tested the effect of standard mitochondrial
      inhibitors such as myxothiazole, antimycin, cyanide and rotenone. All of them
      except rotenone collapsed the DeltaPsim and inhibited respiration. The assay was
      validated by comparing the EC50 of these compounds for inhibiting DeltaPsim and
      respiration. This assay was used to investigate the effect of various
      antimalarial drugs such as chloroquine, tetracycline and a broad spectrum
      antiparasitic drug atovaquone. We observed that only atovaquone collapsed
      DeltaPsim and inhibited parasite respiration within minutes after drug treatment.
      Furthermore, atovaquone had no effect on mammalian DeltaPsim. This suggests that
      atovaquone, shown to inhibit mitochondrial electron transport, also depolarizes
      malarial mitochondria with consequent cellular damage and death.

PMID- 9020101
TI  - Transforming growth factor-beta1 inhibits basal melanogenesis in B16/F10 mouse
      melanoma cells by increasing the rate of degradation of tyrosinase and tyrosinase
      related protein-1.
AB  - Current evidence suggests that melanogenesis is controlled by epidermal paracrine
      modulators. We have analyzed the effects of transforming growth factor-beta1 (TGF
      beta1) on the basal melanogenic activities of B16/F10 mouse melanoma cells. TGF
      beta1 treatment (48 h) elicited a concentration-dependent decrease in basal
      tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (Dopa) oxidase activities, to
      less than 30% of the control values but had no effect on dopachrome tautomerase
      activity (TRP-2). The inhibition affected to similar extents the Dopa oxidase
      activity associated to tyrosinase-related protein-1 (TRP-1) and tyrosinase. This
      inhibition was noticeable between 1 and 3 h after the addition of the cytokine,
      and maximal after 6 h of treatment. The decrease in the enzymatic activity was
      paralleled by a decrease in the abundance of the TRP-1 and tyrosinase proteins.
      TGF-beta1 mediated this effect by increasing the rate of degradation of
      tyrosinase and TRP-1. Conversely, after 48 h of treatment, the expression of the
      tyrosinase gene decreased only slightly, while TRP-1 and TRP-2 gene expression
      was not affected. An increased rate of proteolytic degradation of TRP-1 and
      tyrosinase seems the main mechanism accounting for the inhibitory effect of TGF
      beta1 on the melanogenic activity of B16/F10 cells.

PMID- 9020102
TI  - Refolding process of ovalbumin from urea-denatured state. Evidence for the
      involvement of nonproductive side chain interactions in an early intermediate.
AB  - Ovalbumin contains one cystine disulfide (Cys73-Cys120) and four cysteine
      sulfhydryls (Cys11, Cys30, Cys367, and Cys382) in a single polypeptide chain of
      385 amino acid residues. The refolding mechanism of ovalbumin was investigated
      under disulfide-bonded and disulfide-reduced conditions using the denatured
      protein state, DA, as the starting protein sample. For the preparation of DA, the
      disulfide-intact and disulfide-reduced forms of ovalbumin were denatured by
      protein incubation in 9 M urea at pH 2.2. When DA was placed in a refolding
      buffer, pH 8.2, an intermediate state IN was produced in either the disulfide
      bonded or the disulfide-reduced condition; IN showed about 60% of the native CD
      ellipticity at 222 nm and the intrinsic tryptophan fluorescence with the native
      spectrum peak but with decreased intensity. The formation of IN as detected by
      far UV CD ellipticity was quite rapid and finished within a mixing dead time of
      20 ms. When DA was diluted with an acidic buffer, pH 2.2, a partially folded
      equilibrium intermediate IA with the structural characteristics equivalent to
      those of IN was formed. After the formations of IN and IA, the regains in CD
      ellipticity and tryptophan fluorescence at pH 8.2 followed biphasic kinetics in
      the disulfide-bonded condition but monophasic kinetics in the disulfide-reduced
      condition. As unexpected findings, the native disulfide in DA and IA underwent
      nonproductive disulfide rearrangements in the disulfide-bonded condition at an
      early refolding stage and then was recovered during the subsequent refolding. The
      integrity of overall refolding was confirmed by the observation that the proteins
      refolded for 20 h in the disulfide-bonded and disulfide-reduced conditions
      showed, on differential scanning calorimetry analyses, almost exactly the same
      denaturation temperatures as their native protein counterparts. These results
      were consistent with a refolding process for ovalbumin which includes
      nonproductive side chain-side chain interactions in the early intermediate IN,
      which requires subsequent reorganization for the correct refolding.

PMID- 9020103
TI  - Functional expression of a cDNA to human acyl-coenzyme A:cholesterol
      acyltransferase in yeast. Species-dependent substrate specificity and inhibitor
      sensitivity.
AB  - We have identified two yeast genes with similarity to a human cDNA encoding acyl
      coenzyme A:cholesterol acyltransferase (ACAT). Deletion of both yeast genes
      results in a viable cell with undetectable esterified sterol (Yang, H., Bard, M.,
      Bruner, D. A., Gleeson, A., Deckelbaum, R. J., Aljinovic, G., Pohl, T.,
      Rothstein, R., and Sturley, S. L. (1996) Science 272, 1353-1356). Here, we
      expressed the human cDNA in the yeast double mutant, resulting in high level
      production of ACAT protein, but low in vivo esterification of ergosterol, the
      predominant yeast sterol. The activity of the human enzyme was increased by
      incubation of these cells with 25-hydroxy, cholesterol, an established positive
      regulator of mammalian sterol esterification. In contrast, the yeast enzymes were
      unaffected by this reagent. In vitro microsomal assays indicated no sterol
      esterification in extracts from the double mutant. However, significant activity
      was detected from strains expressing human ACAT when cholesterol was equilibrated
      with the microsomal membranes. The human enzyme in yeast utilized cholesterol as
      the preferred sterol and was sensitive to competitive (S58035) and non
      competitive (DuP 128) ACAT inhibitors. The yeast esterifying enzymes exhibited a
      diminished sterol substrate preference and were sensitive only to S58035. Human
      ACAT had a broad acyl-CoA substrate specificity, the other substrate for this
      reaction. By contrast, the yeast enzymes had a marked preference for specific
      acyl-CoAs, particularly unsaturated C18 forms. These results confirm the yeast
      genes as functional homologs of the human gene and demonstrate that the enzymes
      confer substrate specificity to the esterification reaction in both organisms.

PMID- 9020104
TI  - Effector specificity mutants of the transcriptional activator NahR of naphthalene
      degrading Pseudomonas define protein sites involved in binding of aromatic
      inducers.
AB  - This work reports a genetic analysis of the interactions between NahR, the LysR
      type regulator of the NAH operons for biodegradation of naphthalene in
      Pseudomonas, and its aromatic effectors. Six mutants encoding NahR variants
      responsive to salicylate analogs such as benzoate, which is not an inducer for
      the wild type regulator, were isolated with a polymerase chain reaction-based
      saturation mutagenesis protocol. Most mutants displaying a specific change of
      effector profile bore single amino acid substitutions within a short protein
      segment of 60 residues located at the central portion of the NahR sequence. Some
      of the protein variants exhibited an increased affinity for salicylate and also
      for otherwise suboptimal effectors, with apparent Ks' values 5-100-fold lower
      than those of the wild type NahR protein. In addition, all mutants were activated
      by inducers bearing novel substituents at positions 1 or 2 of the aromatic ring
      and displayed also an enhanced tolerance to changes at positions 3 and 4.
      Correlation between mutations in NahR and the structures of the new effectors
      suggested that protein sites Met116, Arg132, Asn169, and Arg248 are involved in
      effector recognition and binding during the earlier steps of the process leading
      to transcriptional activation of cognate NAH promoters.

PMID- 9020105
TI  - Compensatory regulation of RIalpha protein levels in protein kinase A mutant
      mice.
AB  - The cAMP-dependent protein kinase holoenzyme is assembled from regulatory (R) and
      catalytic (C) subunits that are expressed in tissue-specific patterns. Despite
      the dispersion of the R and C subunit genes to different chromosomal loci,
      mechanisms exist that coordinately regulate the intracellular levels of R and C
      protein such that cAMP-dependent regulation is preserved. We have created null
      mutations in the RIbeta and RIIbeta regulatory subunit genes in mice, and find
      that both result in an increase in the level of RIalpha protein in tissues that
      normally express the beta isoforms. Examination of RIalpha mRNA levels and the
      rates of RIalpha protein synthesis in wild type and RIIbeta mutant mice reveals
      that the mechanism of this biochemical compensation by RIalpha does not involve
      transcriptional or translational control. These in vivo findings are consistent
      with observations made in cell culture, where we demonstrate that the
      overexpression of Calpha in NIH 3T3 cells results in increased RIalpha protein
      without increases in the rate of RIalpha synthesis or the level of RIalpha mRNA.
      Pulse-chase experiments reveal a 4-5-fold increase in the half-life of RIalpha
      protein as it becomes incorporated into the holoenzyme. Compensation by RIalpha
      stabilization may represent an important biological mechanism that safeguards
      cells from unregulated catalytic subunit activity.

PMID- 9020106
TI  - Epstein-Barr virus nuclear antigen 1 forms a complex with the nuclear transporter
      karyopherin alpha2.
AB  - The Epstein-Barr virus (EBV) is implicated in the induction of several
      malignancies. The nuclear antigen 1 (EBNA1) is the only viral protein that is
      expressed consistently in all EBV-associated tumors. EBNA1 is involved in the
      replication and maintenance of the viral episome in the infected cell and
      exhibits oncogenic activity in transgenic mice. Here we report the identification
      of the nuclear transporter karyopherin alpha2 as a cellular partner of EBNA1
      using the yeast "two-hybrid system." Karyopherin alpha2 is also called importin
      alpha or Rch1. The binding to karyopherin alpha2 was mediated through a C
      terminal region of EBNA1 encompassing the nuclear localization signal, whereas
      clones of EBNA1 devoid of the nuclear localization signal failed to bind to
      karyopherin alpha2. The interaction was biochemically confirmed by far-Western
      analysis using bacterially expressed karyopherin alpha2 and karyopherin alpha2
      specific monoclonal antibodies. The nuclear transport of EBNA1 was impaired by
      expression of N-terminally truncated karyopherin alpha2. Zone velocity
      sedimentation in a sucrose gradient indicated that: (i) EBNA1 and Rch1
      colocalize; and (ii) the association of karyopherin alpha2 with high molecular
      weight protein complexes might be impeded by the presence of EBNA1.

PMID- 9020107
TI  - Angiotensin II stimulates phosphorylation of the translational repressor 4E
      binding protein 1 by a mitogen-activated protein kinase-independent mechanism.
AB  - To investigate the molecular basis of the hypertrophic action of angiotensin II
      (AII) in vascular smooth muscle cells (SMC), we have examined the ability of the
      hormone to regulate the function of the translational repressor 4E-binding
      protein 1 (4E-BP1). Addition of AII to quiescent aortic SMC potently increased
      the phosphorylation of 4E-BP1 as revealed by a decreased electrophoretic mobility
      and an increased phosphate content of the protein. The stimulation of 4E-BP1
      phosphorylation was maximal at 15 min and persisted up to 120 min. Results from
      affinity chromatography on m7GTP-agarose demonstrated that AII-induced
      phosphorylation of 4E-BP1 promotes its dissociation from eIF4E in target cells.
      Further characterization of 4E-BP1 phosphorylation by phosphoamino acid analysis
      and phosphopeptide mapping revealed that 4E-BP1 is phosphorylated on eight
      distinct peptides containing serine and threonine residues in AII-treated cells.
      The combination of results obtained from kinetics experiments, phosphopeptide
      analysis of in vitro and in vivo phosphorylated 4E-BP1, and pharmacological
      studies with the MAP kinase kinase inhibitor PD 98059 provided strong evidence
      that the MAP kinases ERK1/ERK2 are not involved in the regulation of 4E-BP1
      phosphorylation in aortic SMC. Together, our results demonstrate that AII
      treatment of vascular SMC leads to hyperphosphorylation of the translational
      regulator 4E-BP1 and to its dissociation from eIF4E by a MAP kinase-independent
      mechanism.

PMID- 9020108
TI  - The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal
      growth factor signaling without disrupting formation of signaling complexes or
      reducing the specific enzymatic activity of Raf kinase.
AB  - We have expressed the mitogenic signaling proteins Src, Ras, Raf-1, Mek (MAP
      kinase kinase), and Erk (MAP kinase) in baculovirus-infected Sf9 insect cells in
      order to study a potential role for the chaperone hsp90 in formation of
      multiprotein complexes. One such complex obtained by immunoadsorption with anti
      Ras antibody of cytosol prepared from cells simultaneously expressing Ras, Raf,
      Mek, and Erk contained Ras, Raf, and Erk. To detect directly the protein-protein
      interactions involved in forming multiprotein complexes, we combined cytosols
      from single infections in vitro in all possible combinations of protein pairs. We
      detected complexes between Ras.Raf, Ras.Src, Raf.Mek, and Raf.Src, but no complex
      containing Erk was obtained by mixing cytosols. Thus, cellular factors appear to
      be required for assembly of the Erk-containing multiprotein complex. One cellular
      factor thought to be involved in signaling protein complex formation is the
      chaperone hsp90, and we show that Src, Raf, and Mek are each complexed with
      insect hsp90. Treatment of Sf9 cells with geldanamycin, a benzoquinone ansamycin
      that binds to hsp90 and disrupts its function, did not decrease coadsorption of
      either Raf or Erk with Ras, although it did decrease the level of cytosolic Raf.
      To study geldanamycin action, we treated rat 3Y1 fibroblasts expressing v-Raf and
      showed that the antibiotic blocked assembly of Raf.hsp90 complexes at an
      intermediate stage of assembly where Raf is still bound to the p60 and hsp70
      components of the assembly mechanism. As in Sf9 cells, Raf levels decline with
      geldanamycin treatment of 3Y1 cells. To determine if geldanamycin affects
      mitogenic response, we treated HeLa cells with epidermal growth factor (EGF) and
      showed that geldanamycin treatment decreased EGF signaling and decreased the
      level of Raf protein without affecting the EGF-mediated increase in Raf kinase
      activity. We conclude that hsp90 is not required for forming complexes between
      the mitogenic signaling proteins or for Raf kinase activity and that EGF
      signaling is decreased indirectly by geldanamycin because the antibiotic
      increases degradation of Raf and perhaps other components of the signaling
      pathway.

PMID- 9020109
TI  - Sp3 is a bifunctional transcription regulator with modular independent activation
      and repression domains.
AB  - Sp3 is a member of the Sp family of transcription factors and binds to DNA with
      affinity and specificity comparable to that of Sp1. We demonstrate that Sp3 is a
      bifunctional transcription factor that can both activate and repress
      transcription. Gene fusion experiments in mammalian cells demonstrate that the
      Sp3 activation potential is distributed over an extensive glutamine-rich N
      terminal region, whereas the repressor activity has been mapped in a 72-amino
      acid region located at the 5' of the zinc finger DNA-binding domain. We
      demonstrated that the repression activity is strictly dependent on the context of
      the DNA-binding sites bound by Sp3. We found that Sp3 represses transcription of
      promoters bearing multiple GAL4 DNA-binding sites, whereas it activates isogenic
      reporters containing a single GAL4-binding site. Transfection experiments in
      Drosophila cells that lack endogenous Sp activity demonstrated that Sp3 does not
      possess an active repression domain that can function in insect cells, rather it
      is a weak transcriptional activator of the c-myc promoter. Our results strongly
      suggest that Sp3 is a dual-function regulator whose activity is dependent upon
      both the promoter and the cellular context.

PMID- 9020110
TI  - The glycosylation of the influenza A virus hemagglutinin by mammalian cells. A
      site-specific study.
AB  - We have characterized the glycans at individual sites on the hemagglutinin of
      three influenza A variants to obtain information on the role of cell-specific
      glycosylation in determining the receptor binding properties of this virus. The
      variants differ in whether they have a glycosylation site at residue 129 on the
      tip of the hemagglutinin and whether amino acid 184 (near to the receptor binding
      site) is His or Asn. We found that all sites on each variant are glycosylated in
      Madin-Darby bovine kidney cells, that the glycosylation is site-specific, and
      that the glycans at the same site in each variant are highly similar. One site
      that is buried in the hemagglutinin trimer contains only oligomannose glycans.
      The remaining sites carry complex glycans of increasing size as the distance of
      the site from the viral membrane decreases. Most of these complex glycans are
      terminated with alpha-galactose residues, a consequence in bovine cells of the
      removal of terminal sialic acids by the viral neuraminidase. Although the glycans
      at residue 129 are among the smallest on the molecule, they are large enough to
      reach the receptor binding pocket on their own and adjacent monomers. The results
      suggest that the reduction in receptor binding observed with Madin-Darby bovine
      kidney cell-grown virus is due to the combined effect of large complex glycans at
      the tip of the hemagglutinin and a His to Asn substitution close to the receptor
      binding pocket.

PMID- 9020111
TI  - Accumulation of pyrraline-modified albumin in phagocytes due to reduced
      degradation by lysosomal enzymes.
AB  - Previous studies suggested that the interaction between proteins modified by
      advanced glycation end products (AGEs) and cells, such as macrophages, may be
      involved in diabetic angiopathy. Pyrraline is one of the AGEs and known to be
      elevated in plasma of diabetic rats and humans, and is present in vascular
      lesions of diabetic and elderly subjects. We examined whether modification of
      albumin by pyrraline influences its degradation by macrophage-like cell line,
      P388D1 cells. Degradation of pyrraline-modified albumin by these cells was
      diminished, causing accumulation of the albumin in these cells. The
      susceptibility of pyrraline-modified albumin to lysosomal proteolytic enzymes was
      reduced by approximately 40% in vitro, while lysosomal activity in the cells per
      se was not affected. This phenomenon was also observed when human monocytes were
      used instead of P388D1 cells. Our results suggest that accumulation of pyrraline
      modified albumin in P388D1 cells is due to the reduced susceptibility of the
      protein to lysosomal enzymatic degradation. Such alterations in the interaction
      between AGEs-modified protein and phagocytes may contribute to angiopathy in
      elderly subjects and patients with diabetes.

PMID- 9020112
TI  - Interactions of mast cell tryptase with thrombin receptors and PAR-2.
AB  - Tryptase is a serine protease secreted by mast cells that is able to activate
      other cells. In the present studies we have tested whether these responses could
      be mediated by thrombin receptors or PAR-2, two G-protein-coupled receptors that
      are activated by proteolysis. When added to a peptide corresponding to the N
      terminus of PAR-2, tryptase cleaved the peptide at the activating site, but at
      higher concentrations it also cleaved downstream, as did trypsin, a known
      activator of PAR-2. Thrombin, factor Xa, plasmin, urokinase, plasma kallikrein,
      and tissue kallikrein had no effect. Tryptase also cleaved the analogous thrombin
      receptor peptide at the activating site but less efficiently. When added to COS-1
      cells expressing either receptor, tryptase stimulated phosphoinositide
      hydrolysis. With PAR-2, this response was half-maximal at 1 nM tryptase and could
      be inhibited by the tryptase inhibitor, APC366, or by antibodies to tryptase and
      PAR-2. When added to human endothelial cells, which normally express PAR-2 and
      thrombin receptors, or keratinocytes, which express only PAR-2, tryptase caused
      an increase in cytosolic Ca2+. However, when added to platelets or CHRF-288
      cells, which express thrombin receptors but not PAR-2, tryptase caused neither
      aggregation nor increased Ca2+. These results show that 1) tryptase has the
      potential to activate both PAR-2 and thrombin receptors; 2) for PAR-2, this
      potential is realized, although cleavage at secondary sites may limit activation,
      particularly at higher tryptase concentrations; and 3) in contrast, although
      tryptase clearly activates thrombin receptors in COS-1 cells, it does not appear
      to cleave endogenous thrombin receptors in platelets or CHRF-288 cells. These
      distinctions correlate with the observed differences in the rate of cleavage of
      the PAR-2 and thrombin receptor peptides by tryptase. Tryptase is the first
      protease other than trypsin that has been shown to activate human PAR-2. Its
      presence within mast cell granules places it in tissues where PAR-2 is expressed
      but trypsin is unlikely to reach.

PMID- 9020113
TI  - Role of gene overlap in the regulation of mRNA translation for mitochondrial
      cytochrome P-450c27/25 in the rat.
AB  - Previously published results have revealed sequence complementarity between the
      5'-terminal regions of mRNAs for hepatic mitochondrial cytochrome P-450c27/ 25
      (c27/25) and serine protease inhibitors (SPI) and predicted a role for this
      sequence overlap in both the regulation of c27/25 mRNA transcription and
      translation. The possibility that c27/25 mRNA forms an RNA duplex with
      complementary sequences of SPI mRNAs in vivo was demonstrated in the rat liver
      and COS-1 cells cotransfected with c27/25 and SPI2.1 plasmids. Quantitative
      evaluation of RNA duplex in COS-1 cells revealed that most of the c27/25 mRNA
      exists in duplex form when SPI2.1 mRNA was present at 5-10-fold that of c27/25
      mRNA, a ratio comparable to that observed between these two RNAs in the liver. In
      cotransfected COS-1 cells with the same ratio of mRNAs, highly significant
      inhibition of the c27/25 mRNA translation (66-75%) was observed, while its
      transcription remained unaffected. The partial inhibition of c27/25 mRNA
      translation, even when most of it exists in duplex form, suggests that RNA duplex
      is undergoing some type of cytoplasmic processing to disengage c27/25 mRNA and
      make it available for translation. These results imply that abundant endogenous
      SPI RNAs are able to regulate the c27/25 gene expression.

PMID- 9020114
TI  - Molecular mechanism of polyamine stimulation of the synthesis of oligopeptide
      binding protein.
AB  - Polyamine stimulation of the synthesis of oligopeptide-binding protein (OppA) was
      shown to occur mainly at the level of translation by measuring OppA synthesis and
      its mRNA level. Several artificial oppA genes were constructed by site-directed
      mutagenesis. These synthesize different kinds of OppA mRNAs: mRNAs differing in
      the size of 5'-untranslated region; mRNAs having the Shine-Dalgarno (SD) sequence
      in a different position; mRNAs having different secondary structure in the region
      of the SD sequence; and fusion mRNAs consisting of the 5'-untranslated region of
      OppA mRNA and the open reading frame of beta-galactosidase. By measuring the
      synthesis of OppA or beta-galactosidase from these mRNAs, we found that the 171
      nucleotide 5'-untranslated region and 145 nucleotides of the ORF of OppA mRNA are
      involved in the polyamine stimulation of OppA synthesis. When the secondary
      structure of the above region of OppA mRNA was analyzed by optimal computer
      folding, it was shown that the degree of polyamine stimulation of OppA protein
      synthesis was dependent on the structure of the SD sequence in addition to its
      position. Loose base pairing of the SD sequence with other regions of the mRNA
      caused strong polyamine stimulation, while intense base pairing of the SD
      sequence with other regions of the mRNA resulted in insignificant or weak
      polyamine stimulation.

PMID- 9020115
TI  - Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and
      evidence for receptor homo-oligomerization.
AB  - The leptin receptor (OB-R) mediates the weight regulatory effects of the
      adipocyte secreted hormone leptin (OB). Previously we have shown that the long
      form of OB-R, expressed predominantly in the hypothalamus, can mediate ligand
      induced activation of signal transducer and activator of transcription factors 1,
      3, and 5 and stimulate transcription via interleukin-6 and hematopoietin receptor
      responsive gene elements. Here we report that deletion and tyrosine substitution
      mutagenesis of OB-R identifies two distinct regions of the intracellular domain
      important for signaling. In addition, granulocyte-colony stimulatory factor
      receptor/OB-R and OB-R/granulocyte-colony stimulatory factor receptor chimeras
      are signaling competent and provide evidence that aggregation of two OB-R
      intracellular domains is sufficient for ligand-induced receptor activation.
      However, signaling by full-length OB-R appears to be relatively resistant to
      dominant negative repression by signaling-incompetent OB-R, suggesting that
      mechanisms exist to permit signaling by the long form of OB-R even in the
      presence [corrected] of excess naturally occurring short form of OB-R.

PMID- 9020116
TI  - Conventional PKC-alpha, novel PKC-epsilon and PKC-theta, but not atypical PKC
      lambda are MARCKS kinases in intact NIH 3T3 fibroblasts.
AB  - Phosphorylation of myristoylated alanine-rich protein kinase C substrate (MARCKS)
      in intact cells has been employed as an indicator for activation of protein
      kinase C (PKC). Specific PKC isoenzymes responsible for MARCKS phosphorylation
      under physiological conditions, however, remained to be identified. In our
      present study using stably transfected NIH 3T3 cell clones we demonstrate that
      expression of constitutively active mutants of either conventional cPKC-alpha or
      novel nPKC-epsilon increased phosphorylation of endogenous MARCKS in the absence
      of phorbol 12,13-dibutyrate in intact mouse fibroblasts, implicating that each of
      these PKC isoforms itself is sufficient to induce enhanced MARCKS
      phosphorylation. Similarly, ectopic expression of a constitutively active mutant
      of PKC-theta significantly increased MARCKS phosphorylation compared to vector
      controls, identifying PKC-theta as a MARCKS kinase. The PKC-specific inhibitor GF
      109203X (bisindolylmaleimide I) reduced MARCKS phosphorylation in intact cells at
      a similar dose-response as enzymatic activity of recombinant isoenzymes cPKC
      alpha, nPKC-epsilon, and nPKC-theta in vitro. Consistently, phorbol 12,13
      dibutyrate-dependent MARCKS phosphorylation was significantly reduced in cell
      lines expressing dominant negative mutants of either PKC-alpha K368R or (dominant
      negative) PKC-epsilon K436R. The fact, that the constitutively active PKC-lambda
      A119E mutant did not alter the MARCKS phosphorylation underscores the assumption
      that atypical PKC isoforms are not involved in this process. We conclude that
      under physiological conditions, conventional cPKC-alpha and novel nPKC-epsilon,
      but not atypical aPKC-lambda are responsible for MARCKS phosphorylation in intact
      NIH 3T3 fibroblasts.

PMID- 9020117
TI  - Subsets of epidermal growth factor receptors during activation and endocytosis.
AB  - Mutation of the autophosphorylation sites of receptor protein-tyrosine kinases
      alters ligand dependent internalization and down-regulation, indicating a
      critical role for these sites in receptor processing. Currently, no differences
      in receptor processing based on an individual autophosphorylation site have been
      defined. By using a glutathione S-transferase fusion protein containing the src
      homology 2 domains of phospholipase C-gamma1 to specifically recognize tyrosine
      992 on the EGF receptor (Tyr(P)992), we have found differences in this
      subpopulation of receptors. Following EGF stimulation, the number of Tyr(P)992
      receptors increased 2-fold over receptors identified by an antibody that
      recognizes activated EGF receptors (alpha-Act. EGFR) in A431 cells. Confocal
      fluorescence microscopy showed that Tyr(P)992 receptors underwent endocytosis at
      a slower rate and did not rapidly concentrate in juxtanuclear bodies. Tyr(P)992
      receptors were associated with more SOS, Ras-GTPase activating protein,
      phosphatidylinositol 3-kinase, and SHPTP2/syp, but less Grb2, than receptors in
      the general population, and these receptors were more heavily phosphorylated than
      the general population of active receptors. These findings suggest that
      autophosphorylation status is relevant to the endocytosis, degradation, and
      effector molecule interaction of individual EGF receptors. Further investigations
      based on phosphorylation status should provide new insights into how receptor
      protein-tyrosine kinase signaling is regulated.

PMID- 9020118
TI  - prl mutations in the Escherichia coli secG gene.
AB  - SecG, an integral membrane component of the Escherichia coli preprotein
      translocase, contributes to the efficiency of the export process by undergoing
      cycles of topology inversion in the membrane, coupled with the insertion
      deinsertion cycles of SecA. We have previously identified sec alleles of secG
      that cause a generalized secretion defect. In this study, by screening
      mutagenized secG libraries for suppressors of a malE signal sequence mutation, we
      isolated prl alleles of secG. By analogy with secY/prlA, secA/prlD, and
      secE/prlG, secG could therefore be called secG/prlH. The prlH mutations affect 13
      codons distributed along the secG sequence, and none map to the codons affected
      by sec mutations. prlH suppressors suppress a variety of signal sequence
      mutations and they allow export of alkaline phosphatase lacking its entire signal
      sequence. Although secG was not identified in previous selections for prl
      mutants, several prlH alleles are as strong as the strongest known prlG alleles
      of secE. Some prlH alleles can also promote the export of alkaline phosphatase
      fused to predicted cytoplasmic domains of UhpT, an integral membrane protein.
      These results support the notion that SecG contributes to signal sequence
      recognition, and suggest that it may also contribute to the topology of integral
      membrane proteins.

PMID- 9020119
TI  - Hyperphosphorylation of heat shock transcription factor 1 is correlated with
      transcriptional competence and slow dissociation of active factor trimers.
AB  - In the course of its activation by heat and other stresses, the inactive monomer
      of human heat shock transcription factor 1 (HSF1) is converted to a DNA-binding
      homotrimer and is hyperphosphorylated. At least four Ser/Thr residues in HSF1
      appeared to be inducibly phosphorylated during heat shock. Ser/Thr protein kinase
      inhibitors inhibited, and protein phosphatase inhibitor calyculin A and phorbol
      ester enhanced, hsp70-CAT reporter gene expression but not heat shock element DNA
      binding activity in HeLa cells undergoing a moderate heat shock. Calyculin A (5
      20 nM) caused hyperphosphorylation of HSF1, the extent of which was comparable to
      that produced by moderate to severe heat shock. Upon recovery from a 42 degrees
      C/30 min-heat shock, HSF1 trimers disassembled quantitatively within 2 h.
      Calyculin A interfered with the dissociation of HSF1 trimers. Thus,
      hyperphosphorylation increases the effective half-life of the HSF1 trimer, which
      may prolong factor activity subsequent to heat shock. Hyperphosphorylation also
      dramatically stimulated the transactivation function of HSF1: exposure to
      calyculin A of cells induced to form inactive HSF1 trimers resulted in the
      conversion of the inactive to active trimers. Given that deletion of certain
      sequences renders HSF1 constitutively active, these results suggested that the
      activation of HSF1 trimers by calyculin A was a consequence of
      hyperphosphorylation of HSF1 rather than of a downstream factor.

PMID- 9020120
TI  - Molecular determinants of arg-gly-asp ligand specificity for beta3 integrins.
AB  - The Arg-Tyr-Asp (RYD) and Arg-Gly-Asp (RGD) sequences within the third
      complementarity-determining region of the heavy chain (H3) of murine recombinant
      Fab molecules OPG2 and AP7, respectively, are responsible for their specific
      binding to the platelet integrin alphaIIbbeta3. In this study, we evaluated the
      influence of divalent cation composition and single amino acid substitutions at
      key positions within H3 on the selectivity of these Fab molecules for integrin
      alphaIIbbeta3 versus the vitronectin receptor alphaVbeta3. The parent Fab
      molecule OPG2 (H3 sequence, HPFYRYDGGN) binds selectively to alphaIIbbeta3 and
      not at all to any other RGD-cognitive integrin, particularly alphaVbeta3, under
      any divalent cation conditions. The binding of the AP7 Fab molecule (HPFYRGDGGN)
      to alphaIIbbeta3 is not affected by the relative composition of calcium,
      magnesium or manganese. However, AP7 binding to alphaVbeta3, either expressed by
      M21 cells or as the purified integrin, is supported by manganese and inhibited by
      calcium. If the flanking asparagine 108 residue within the AP7 H3 loop is
      replaced by alanine (HPFYRGDGGA), the resulting Fab molecule AP7.4 binds
      selectively to alphaVbeta3 in a cation-dependent manner, but does not bind at all
      to alphaIIbbeta3 under any conditions. AP7.4 binding to alphaVbeta3 is supported
      by manganese, completely inhibited by calcium, and largely unaffected by
      magnesium. This behavior mimics that of the adhesive protein, osteopontin,
      another ligand that binds preferentially to alphaVbeta3. Despite these
      differences in specificity for alphaIIbbeta3 and alphaVbeta3, AP7 and AP7.4
      remain selective for the beta3 integrins and do not bind to cell lines that
      express the RGD-cognitive integrins alphaVbeta5 or alpha5beta1. These results
      confirm that subtle changes in the amino acid composition immediately flanking
      the RGD or RYD motifs can have a profound effect on beta3 integrin specificity,
      most likely because they influence the juxtaposition of the arginine and
      aspartate side chains within the extended RGD loop sequence.

PMID- 9020121
TI  - Tissue-specific expression of unique mRNAs that encode proglucagon-derived
      peptides or exendin 4 in the lizard.
AB  - Glucagon-like peptide 1 stimulates insulin secretion and inhibits glucagon
      secretion, gastric emptying, and feeding, suggesting it may be biologically
      useful for the treatment of diabetes. A lizard glucagon-like peptide 1 (GLP-1)
      related peptide, exendin 4, binds to the GLP-1 receptor and mimics the actions of
      GLP-1 in vivo. To determine the genetic relationship between exendin 4 and GLP-1,
      we analyzed the structure and expression of pancreatic and intestinal proglucagon
      mRNAs in the reptile Heloderma suspectum. Two different proglucagon cDNAs (lizard
      proglucagon I (LPI) and lizard proglucagon II (LPII)), with unique 3'
      untranslated regions were identified. Two LPI mRNA transcripts, approximately 1.6
      and 2.1 kilobases, encoded glucagon and GLP-1 but not GLP-2 and were restricted
      in expression to the pancreas. In contrast, a 1.1-kilobase LPII mRNA transcript,
      encoding glucagon, GLP-1, and GLP-2 utilized a different 3'-untranslated region
      and was expressed in both pancreas and intestine. Lizard proglucagon mRNA
      transcripts were not detectable by reverse transcription-polymerase chain
      reaction or Northern blotting in salivary gland. A single class of lizard
      salivary gland proexendin cDNAs encoded the sequence of exendin 4 and a 45-amino
      acid exendin NH2-terminal peptide. Exendin mRNA transcripts were expressed in the
      salivary gland, but not pancreas or intestine. These data demonstrate that GLP-1
      and exendin 4 represent related yet distinct peptides encoded by different genes
      in the lizard.

PMID- 9020122
TI  - Identification of a molluscan homologue of the neuroendocrine polypeptide 7B2.
AB  - In vertebrates, interaction of prohormone convertase 2 (PC2) with the highly
      conserved polypeptide 7B2 is essential for transport and maturation of proPC2 in
      the regulated secretory pathway. In vitro, 7B2 displays a strong inhibitory
      activity toward PC2. Here, we characterize a cDNA encoding the first invertebrate
      7B2-related protein (L7B2) from the brain of the mollusc Lymnaea stagnalis. The
      overall amino acid sequence identity between L7B2 and its vertebrate counterparts
      is surprisingly low (29%) and is restricted to a few small stretches of amino
      acid residues. Of particular interest are a conserved proline-rich region in the
      middle portion of the L7B2 sequence and a repeated conserved region in the
      carboxyl-terminal domain. Synthetic peptides corresponding to the carboxyl
      terminal regions inhibit Lymnaea PC2 enzyme activity in extracts of insulin
      producing neurons, in which both L7B2 and Lymnaea PC2 are abundantly expressed.
      Moreover, the peptides inhibit mouse PC2 enzyme activity. Our cloning of
      invertebrate 7B2 helps to delineate residues that are important for 7B2-PC2
      interaction.

PMID- 9020123
TI  - UDP-galactofuranose precursor required for formation of the lipopolysaccharide O
      antigen of Klebsiella pneumoniae serotype O1 is synthesized by the product of the
      rfbDKPO1 gene.
AB  - The O-side-chain polysaccharide in the lipopolysaccharide of Klebsiella
      pneumoniae O1 is based on a backbone structure of repeat units of [-->3)-beta-D
      Galf-(1-->3)-alpha-D-Galp-(1-->]; this structure is termed D-galactan I. The rfb
      (O-antigen biosynthesis) gene cluster directs the synthesis of D-galactan I and
      consists of six genes termed rfbA-FKPO1. In this paper we show that rfbDKPO1
      encodes a UDP-galactopyranose mutase (NAD(P)H-requiring) (EC 5.4.99. 9), which
      forms uridine 5'-(trihydrogen diphosphate) P'-alpha-D-galactofuranosyl ester (UDP
      Galf), the biosynthetic precursor of galactofuranosyl residues. The deduced amino
      acid sequence of rfbDKPO1 shows 85% and 37.5% identity to the rfbDKPO8 gene of K.
      pneumoniae serotype O8 and the glf gene of Escherichia coli, respectively. The
      molecular mass of the purified RfbDKPO1 enzyme is 45 kDa as determined by SDS
      polyacrylamide gel electrophoresis, while gel filtration revealed a molecular
      mass of 92 kDa, suggesting a dimeric structure for the native protein. The
      rfbDKPO1 gene product interconverts uridine 5'-(trihydrogen diphosphate) P'-alpha
      D-galactopyranosyl ester (UDP-Galp) and UDP-Galf. Unlike Glf, RfbDKPO1 showed a
      requirement for NADH or NADPH, which could not be replaced by NAD or NADP.
      RfbDKPO1 was used to synthesize milligram quantities of UDP-Galf, allowing this
      compound to be purified and fully characterized in an intact form for the first
      time. The structure of UDP-Galf was proven by NMR spectroscopy.

PMID- 9020124
TI  - Tissue-specific stabilization of the thyroid hormone beta1 nuclear receptor by
      phosphorylation.
AB  - The present study evaluated the expression and regulation of endogenous thyroid
      hormone receptors (TRs) in cultured cells. In COS-1 cells, the endogenous TR,
      subtype beta1 (TRbeta1), but not subtype beta2 or alpha1, was induced to express
      by okadaic acid (OA) in a concentration-dependent manner. The induced TRbeta1 had
      immunoreactivity and partial V8 proteolytic maps similar to those of the
      transfected and in vitro translated human TRbeta1 (h-TRbeta1). The OA-induced
      expression of endogenous TRbeta1 was, however, not observed in a variety of other
      cultured cell lines tested, indicating that the induction was cell type
      dependent. TRbeta1 induced by OA was a multisite phosphorylated protein, in which
      serine and threonine in a ratio of 10:1 were phosphorylated. The induced TRbeta1
      was functional as it could mediate the thyroid hormone-dependent transcriptional
      activity via several thyroid hormone response elements. The induction of
      endogenous TRbeta1 expression by OA was not accompanied by an increase in mRNA
      levels but was the result of an increase in the stability of the TRbeta1 protein.
      This is the first report to indicate that one of the mechanisms by which the TR
      isoforms are differentially expressed is via the tissue-specific stabilization of
      the TR isoform proteins. Furthermore, this selective stability of TRbeta1 could
      be conferred by phosphorylation.

PMID- 9020125
TI  - Differential surface expression and phosphorylation of the N-methyl-D-aspartate
      receptor subunits NR1 and NR2 in cultured hippocampal neurons.
AB  - The trafficking and phosphorylation of the NR1 and NR2 subunits of the N-methyl-D
      aspartate-type glutamate receptor complex were studied in cultured rat
      hippocampal neurons. Surface expression was examined by modifying surface
      receptors via treatment of intact neurons with either the protease chymotrypsin
      or the cross-linking reagent bis(sulfosuccinimidyl)suberate, followed by
      quantification of anti-NR1 and anti-NR2B Western blot immunostaining. These
      studies revealed that only 40-50% of total NR1 immunoreactivity is found at the
      cell surface, as compared to more than 90% of total NR2B immunoreactivity.
      Metabolic labeling of the cultures with 32P revealed that NR2 subunits are highly
      phosphorylated under basal conditions, whereas basal phosphorylation of NR1
      subunits is barely detectable. Following stimulation of the cultures with
      glutamate/glycine or phorbol esters, NR1 phosphorylation was found to be enhanced
      by 3-5-fold, whereas phosphorylation of NR2 subunits was enhanced by less than 2
      fold. To determine whether the difference in the basal NR1 versus NR2
      phosphorylation could be due to tyrosine phosphorylation of NR2, phosphoamino
      acid analyses of NR2 were performed. These analyses revealed phosphorylation on
      serine but not on threonine or tyrosine; immunoprecipitation and deglycosylation
      experiments using anti-phosphotyrosine antibodies confirmed that NR2 subunits in
      the primary hippocampal cultures are not detectably phosphorylated on tyrosine
      residues. These results demonstrate that the NR1 and NR2 subunits, which assemble
      into heteromeric complexes to form functional N-methyl-D-aspartate receptors, are
      trafficked in neurons with differential efficiency to the plasma membrane and
      exhibit different levels of basal versus stimulated serine phosphorylation.

PMID- 9020126
TI  - Comparative activity of ADP-ribosylation factor family members in the early steps
      of coated vesicle formation on rat liver Golgi membranes.
AB  - We have compared the abilities of mammalian ADP-ribosylation factors (ARFs) 1, 5,
      and 6 and Saccharomyces cerevisiae ARF2 to serve as substrates for the rat liver
      Golgi membrane guanine nucleotide exchange factor and to initiate the formation
      of clathrin- and coatomer protein (COP) I-coated vesicles on these membranes.
      While Golgi membranes stimulated the exchange of GTPgammaS for GDP on all of the
      ARFs tested, mammalian ARF1 was the best substrate, with an apparent Km of 5
      microM. In all cases myristoylation of ARF was required for stimulation. Agents
      that inhibit the Golgi membrane guanine nucleotide exchange factor (the fungal
      metabolite brefeldin A and trypsin treatment) selectively inhibited the guanine
      nucleotide exchange on mammalian ARF1. Taken together, these data indicate that
      of the ARFs tested, only mammalian ARF1 is activated efficiently by the Golgi
      guanine nucleotide exchange factor. The other ARFs are activated mainly by
      another mechanism, possibly phospholipid-mediated. Once activated, all of the
      membrane-associated, myristoylated ARFs promoted the recruitment of coatomer to
      about the same extent. Mammalian ARFs 1 and 5 were the most effective in
      promoting the recruitment of the AP-1 adaptor complex, whereas yeast ARF2 was the
      least active. These data indicate that the specificity for ARF action on the
      Golgi membranes is primarily determined by the Golgi guanine nucleotide exchange
      factor, which has a strong preference for myristoylated mammalian ARF1.

PMID- 9020127
TI  - Three amino acid substitutions selectively disrupt the activation but not the
      repression function of the glucocorticoid receptor N terminus.
AB  - A 210-amino acid region, termed enh2, near the N terminus of the rat
      glucocorticoid receptor, is necessary for both transcriptional activation and
      repression. The mechanism(s) of transcriptional regulation conferred by this
      region, however, are poorly understood. We screened in Saccharomyces cerevisiae a
      library of random mutants in the enh2 region of a constitutive glucocorticoid
      receptor derivative and isolated a series of multiply substituted receptors that
      are specifically defective in transcriptional activation. Although many
      substitutions in this area were tolerated, three amino acid substitutions (E219K,
      F220L, and W234R) within a 16-amino acid region were sufficient to disrupt the
      enh2 transcriptional activation function both in yeast and in mammalian cells.
      Although this region is rich in acidic residues, the conserved tryptophan at
      position 234 appears to be a more critical feature for enh2 activity; hydrophobic
      but not charged residues were tolerated at this position. Notably, the mutants
      uncoupled the activation and repression functions of enh2, as the activation
      defective isolates remained competent for repression of AP-1 at the composite
      response element plfG.

PMID- 9020128
TI  - Evidence for electron transfer-dependent formation of a nitrogenase iron protein
      molybdenum-iron protein tight complex. The role of aspartate 39.
AB  - Nitrogenase-catalyzed substrate reduction reactions require the association of
      the iron (Fe) protein and the molybdenum-iron (MoFe) protein, electron transfer
      from the Fe protein to the MoFe protein coupled to the hydrolysis of MgATP,
      followed by protein-protein complex dissociation. This work examines the role of
      MgATP hydrolysis and electron transfer in the dissociation of the Fe protein-MoFe
      protein complex. Alteration of aspartate 39 to asparagine (D39N) in the
      nucleotide binding site of Azotobacter vinelandii Fe protein by site-directed
      mutagenesis resulted in an Fe protein-MoFe protein complex that did not
      dissociate after electron transfer. While the D39N Fe protein-MoFe protein
      complex was inactive in all substrate reduction reactions, the complex catalyzed
      both reductant-dependent and reductant-independent MgATP hydrolysis. Once docked
      to the MoFe protein, the D39N Fe protein was found to transfer one electron to
      the MoFe protein requiring MgATP hydrolysis, with an apparent first order rate
      constant of 0.02 s-1 compared with 140 s-1 for the wild-type Fe protein. Only
      following electron transfer to the MoFe protein did the D39N Fe protein form a
      tight complex with the MoFe protein, with no detectable dissociation rate. This
      was in contrast with the dissociation rate constant of the wild-type Fe protein
      from the MoFe protein following electron transfer of 5 s-1. Chemically oxidized
      D39N Fe protein with MgADP-bound did not form a tight complex with the MoFe
      protein, showing a dissociation rate similar to chemically oxidized wild-type Fe
      protein (3 s-1 for D39N Fe protein and 6 s-1 for wild-type Fe protein). These
      results suggest that electron transfer from the Fe protein to the MoFe protein
      within the protein-protein complex normally induces conformational changes which
      increase the affinity of the Fe protein for the MoFe protein. A model is
      presented in which Asp-39 participates in a nucleotide signal transduction
      pathway involved in component protein-protein dissociation.

PMID- 9020129
TI  - Roles of transmembrane prolines and proline-induced kinks of the
      lutropin/choriogonadotropin receptor.
AB  - The lutropin/choriogonadotropin receptor is a seven-helix transmembrane (TM)
      receptor. A unique feature of TM helices is the content of Pro, which generally
      is absent in alpha helices of globular proteins. Because Pro disrupts helices and
      introduces a approximately 26 degrees kink, it has been speculated that Pro plays
      a crucial role in the structure of TM helices, exoloops, and cytoloops of TM
      receptors. To examine the roles of the five TM Pros of the
      lutropin/choriogonadotropin receptor, these residues were individually
      substituted. Mutant receptors were examined for surface expression, hormone
      binding, and cAMP induction. Surface expression was monitored after introducing
      the flag epitope into the receptors. Flag epitopes slightly affected cAMP
      induction but not hormone binding or surface expression of receptors as monitored
      by immunofluorescence microscopy and 125I-anti-flag antibody. The results
      indicate that Pro479 in TM 4 and Pro598 in TM 7 play important yet contrasting
      roles. Pro479 is crucial for hormone binding at the cell surface but not after
      solubilization of the receptor. This is more likely due to the Pro side chain
      than the Pro-induced kink. Pro598 is important for surface expression. The kinks
      of Pro463 of TM 4, Pro562 of TM 6, or Pro591 of TM 7 are not important because
      the substitution of Phe for these residues did not significantly impact surface
      expression, hormone binding, and cAMP induction.

PMID- 9020130
TI  - Caged nicotinic acid adenine dinucleotide phosphate. Synthesis and use.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is a metabolite of NADP
      with Ca2+ mobilizing activity. The Ca2+ release mechanism activated by NAADP as
      well as the Ca2+ stores that it acts on are different from those activated by
      either cyclic ADP-ribose or inositol 1,4,5-trisphosphate (IP3) (Lee, H. C., and
      Aarhus, R. (1995) J. Biol. Chem. 270, 2152-2157). In order to demonstrate
      unambiguously that NAADP can mobilize Ca2+ stores in live cells, a caged analog
      was synthesized by reacting NAADP with 1-(2-nitrophenyl)diazoethane. Anion
      exchange high pressure liquid chromatography (HPLC) was used to purify one
      particular caged form from the mixture of products. Phosphate analyses following
      specific enzymatic cleavage indicate that the caging group is on the 2'
      phosphate. This is confirmed by 31P NMR spectroscopy, showing that the 2'
      phosphate of the caged compound exhibits an altered chemical shift of -2.6 ppm as
      compared with 2.3 ppm determined for the 2'-phosphate of NAADP. Caged NAADP had
      no Ca2+ releasing activity at a concentration as high as 1 micro;M when tested on
      sea urchin egg microsomes. After photolysis, it released Ca2+, was effective in
      nanomolar range, and was indistinguishable from authentic NAADP. The regeneration
      of NAADP after photolysis was also confirmed by HPLC analyses. The analog is
      particularly susceptible to UV and can be efficiently photolyzed using a
      spectrofluorimeter. To demonstrate its utility in live cells, caged NAADP was
      microinjected into sea urchin eggs. Photolysis effectively regenerated NAADP and
      activated Ca2+ oscillations in the eggs. Removal of external Ca2+ did not prevent
      the Ca2+ oscillations but only delayed the second Ca2+ peak by about 45 s,
      indicating that the oscillations are due to release from internal stores and not
      caused by Ca2+ influx. A mechanism based on sensitization of the Ca2+ release by
      Ca2+ loading is proposed to account for the Ca2+ oscillation observed.

PMID- 9020131
TI  - Reglucosylation of N-linked glycans is critical for calnexin assembly with T cell
      receptor (TCR) alpha proteins but not TCRbeta proteins.
AB  - Association of calnexin with newly synthesized glycoproteins involves recognition
      of monoglucosylated glycans, generated in the endoplasmic reticulum via initial
      removal of two glucose (Glc) residues from immature glycan chains by glucosidase
      enzymes (Glc trimming), or addition of a single Glc residue to fully trimmed
      glycans by glucosyltransferase enzymes (reglucosylation). While it has been
      established that creation of monoglucosylated glycans is important for chaperone
      binding, it is unknown if most proteins require both deglucosylation and
      reglucosylation for calnexin assembly or if initial Glc trimming is sufficient.
      Here, we studied the deglucosylation and reglucosylation of two related
      glycoproteins, the alpha and beta subunits of the T cell receptor (TCR) complex,
      and their assembly with calnexin in BW thymoma cells. Our data demonstrate that
      TCRalpha/beta glycoproteins undergo multiple cycles of Glc removal and addition
      within the endoplasmic reticulum and that numerous reglucosylated proteins
      assemble with calnexin, including TCRalpha/beta glycoproteins. Importantly, the
      current study shows that TCRbeta proteins, but not TCRalpha proteins, effectively
      associate with calnexin under conditions of functional Glc trimming but impaired
      reglucosylation. These data demonstrate that reglucosylated proteins associate
      with lectin-like chaperones in vivo and provide evidence that reglucosylation is
      of differential importance for the association of individual, indeed similar,
      glycoproteins with calnexin.

PMID- 9020132
TI  - Phosphatidylinositol-3 kinase is necessary for 12-O-tetradecanoylphorbol-13
      acetate-induced cell transformation and activated protein 1 activation.
AB  - Phorbol esters, which activate isoforms of protein kinase C, are general
      activators of the transcription factor activated protein 1 (AP-1). The pathway
      involved in this signal transduction is not very clear. Currently, little is
      known about whether phosphatidylinositol-3 (PI-3) kinase plays any role in
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced signal
      transduction. We demonstrate here that TPA not only has markedly synergistic
      effects on insulin-induced PI-3 kinase activity, but it also can induce PI-3
      kinase activity and the PI-3 phosphates by itself. We also found that insulin, a
      PI-3 kinase activator, enhanced TPA-induced AP-1 trans-activation and
      transformation in JB6 promotion-sensitive cells. Furthermore, wortmannin and
      LY294002, two PI-3 kinase inhibitors, markedly decreased AP-1 activity induced by
      insulin, TPA, or TPA and insulin and inhibited JB6 promotion-sensitive cell
      transformation induced by TPA or TPA and insulin. Most importantly, constitutive
      overexpression of the dominant negative PI-3 kinase P85 mutants completely
      blocked insulin- or TPA-induced AP-1 trans-activation and TPA-induced cell
      transformation. All evidence from present studies suggests that PI-3 kinase acts
      as a mediator in TPA-induced AP-1 activation and transformation in JB6 cells.

PMID- 9020133
TI  - cGMP stimulation of cystic fibrosis transmembrane conductance regulator Cl-
      channels co-expressed with cGMP-dependent protein kinase type II but not type
      Ibeta.
AB  - In order to investigate the involvement of cGMP-dependent protein kinase (cGK)
      type II in cGMP-provoked intestinal Cl- secretion, cGMP-dependent activation and
      phosphorylation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl-
      channels was analyzed after expression of cGK II or cGK Ibeta in intact cells. An
      intestinal cell line which stably expresses CFTR (IEC-CF7) but contains no
      detectable endogenous cGK II was infected with a recombinant adenoviral vector
      containing the cGK II coding region (Ad-cGK II) resulting in co-expression of
      active cGK II. In these cells, CFTR was activated by membrane-permeant analogs of
      cGMP or by the cGMP-elevating hormone atrial natriuretic peptide as measured by
      125I- efflux assays and whole-cell patch clamp analysis. In contrast, infection
      with recombinant adenoviruses expressing cGK Ibeta or luciferase did not convey
      cGMP sensitivity to CFTR in IEC-CF7 cells. Concordant with the activation of CFTR
      by only cGK II, infection with Ad-cGK II but not Ad-cGK Ibeta enabled cGMP
      analogs to increase CFTR phosphorylation in intact cells. These and other data
      provide evidence that endogenous cGK II is a key mediator of cGMP-provoked
      activation of CFTR in cells where both proteins are co-localized, e. g.
      intestinal epithelial cells. Furthermore, they demonstrate that neither the
      soluble cGK Ibeta nor cAMP-dependent protein kinase are able to substitute for
      cGK II in this cGMP-regulated function.

PMID- 9020134
TI  - The proton-translocating NADH-quinone oxidoreductase (NDH-1) of thermophilic
      bacterium Thermus thermophilus HB-8. Complete DNA sequence of the gene cluster
      and thermostable properties of the expressed NQO2 subunit.
AB  - The genes encoding the proton-translocating NADH-quinone oxidoreductase (NDH-1)
      of a thermophilic bacterium Thermus thermophilus HB-8 were cloned and sequenced.
      They constitute a cluster that is composed of 14 structural genes and contains no
      unidentified reading frames. All of the 14 structural genes, which are designated
      NQO1-14, encode subunits homologous to those of Paracoccus denitrificans NDH-1,
      respectively, and are arranged in the same order as other bacterial NDH-1 genes.
      T. thermophilus NDH-1 contains at most nine putative iron-sulfur cluster binding
      sites, eight of which are commonly found in other organisms. The T. thermophilus
      NQO2 subunit was expressed in Escherichia coli. The expressed subunit bears a
      single [2Fe-2S] cluster whose optical and EPR properties are very similar to
      those of N1a cluster in the P. denitrificans NQO2 subunit (Yano, T., Sled', V.D.,
      Ohnishi, T., and Yagi, T. (1994) Biochemistry 33, 494-499). These results
      strongly suggest that the T. thermophilus NDH-1 is similar to other NDH-1 enzyme
      complexes in terms of subunit and cofactor composition. The T. thermophilus NQO2
      subunit displayed much higher stability than the mesophilic equivalent and its
      iron-sulfur cluster remained intact even after incubation for 3 h at 65 degrees C
      under anaerobic conditions. With the advantage of thermostability, the T.
      thermophilus NDH-1 provides a great model system to investigate the structure
      function relationship of the NDH-1 enzyme complexes.

PMID- 9020135
TI  - Guide RNA-independent and guide RNA-dependent uridine insertion into cytochrome b
      mRNA in a mitochondrial lysate from Leishmania tarentolae. Role of RNA secondary
      structure.
AB  - A primer extension assay was used for the detection of uridine insertions
      occurring in vitro in synthetic pre-edited cytochrome b mRNA during incubation
      with a Leishmania tarentolae mitochondrial extract. Two different activities were
      detected that inserted uridines within the first two editing sites: one that is
      dependent on the secondary structure of the mRNA but is independent of both
      exogenous and endogenous guide RNA, and a second that does not put the same
      structural constraints on the mRNA, but is dependent on the presence of a cognate
      guide RNA.

PMID- 9020136
TI  - Activation of the Sap-1a transcription factor by the c-Jun N-terminal kinase
      (JNK) mitogen-activated protein kinase.
AB  - Ternary complex factors (TCFs) bind to the serum response element in the c-fos
      promoter and mediate its activation by many extracellular stimuli. Some of these
      stimuli activate the ERK subclass of mitogen-activated protein kinases (MAPKs)
      that target the TCF Sap-1a. We show that Sap-1a is also phosphorylated by the
      stress-activated JNK subclass of MAPKs leading to stimulation of both c-fos serum
      response element and E74-site-dependent transcription in RK13 cells. Several JNK
      1 phosphorylation sites were mapped within Sap-1a, and mutation of these sites
      affected the transactivation mediated by Sap-1a and JNK-1. The impact of these
      phosphorylation sites varied at different promoters and was dependent on whether
      Sap-1a was stimulated by ERK-1 or JNK-1. Additionally, a comparison of Sap-1a
      with another TCF, Elk-1, revealed that these proteins behaved differently to
      stimulation by ERK-1 and JNK-1. Furthermore, activation of Sap-1a by JNK-1 was
      inhibited by the p38(MAPK) in RK13 cells, possibly by competition for a common
      upstream activator. Altogether, our data suggest that Sap-1a plays an important
      role in the nuclear response elicited by cellular stress.

PMID- 9020137
TI  - Circular dichroic spectroscopy of N-acetylglucosaminyltransferase V and its
      substrate interactions.
AB  - beta-1,6-N-Acetylglucosaminyltransferase V (EC 2.4.1.155) catalyzes the transfer
      of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in beta(1,6)-linkage to the
      alpha(1,6)-linked mannose of N-linked oligosaccharides. Circular dichroism (CD)
      was used to investigate the secondary structure of a recombinant, soluble form of
      the enzyme and its interaction with UDP-GlcNAc and an inhibitory substrate
      analog. The CD spectrum of the apoenzyme indicated the presence of small amounts
      of beta-structure and substantial amounts (>50%) of alpha-helicity. The CD
      spectra of solutions containing UDP-GlcNAc and different ratios of UDP
      GlcNAc:enzyme were measured. Interestingly, the spectrum of each mixture could
      not be accounted for by simple additivity of the two individual spectra,
      indicating a change in environment of the chromophores and/or a conformational
      change of the substrate or protein concomitant with binding. Similar results were
      obtained with mixtures of UDP and the enzyme. Analysis of the CD difference
      spectra at three wavelengths yielded an estimated average Kd of 4.4 mM for UDP
      GlcNAc and 3.8 mM for UDP. By contrast, addition of the CD spectrum of an
      inhibitory substrate analog of its oligosaccharide acceptor substrate and the CD
      spectrum of the enzyme could account for that observed of an inhibitor-enzyme
      mixture; moreover, addition of the inhibitor to a mixture of UDP-GlcNAc and
      enzyme did not alter the Kd associated with UDP-GlcNAc binding to the enzyme.
      These results and kinetic studies reported herein suggest an ordered reaction in
      which UDP-GlcNAc binds first to the enzyme, followed by the sequential binding of
      the trisaccharide substrate.

PMID- 9020139
TI  - Selective photoaffinity labeling of the inositol polyphosphate binding C2B
      domains of synaptotagmins.
AB  - Synaptotagmin (Syt) II, a synaptic vesicle protein containing two copies of
      highly conserved protein kinase C homology regions known as the C2A and C2B
      domains, acts as a Ca2+ sensor and provides both phospholipid and inositol
      polyphosphate (IPn) recognition domains important in endo- and exocytosis. Four
      photoaffinity analogues of IP3, IP4, and IP6 containing a P-1- or P-2-linked 4
      benzoyldihydrocinnamidyl (BZDC) photophore were used to label glutathione S
      transferase (GST) fusion constructs of the Syt II-C2A and C2B domains. The P-2
      linked [3H]BZDC-IP6 showed efficient, IP6-displaceable labeling of the GST-Syt II
      C2B. The rank order of photocovalent modification paralleled the order of
      competitive displacement: IP6 (P-2-linked) > IP4 > IP3. The P-1-linked [3H]BZDC
      IP6 failed to label the C2B domains. The GST-Syt III-C2B domain, which lacks IP6
      binding affinity, also failed to undergo labeling by P-2-linked [3H]BZDC-IP6.
      When mixtures of the 32-amino acid basic peptide corresponding to the essential
      IPn binding region of the Syt II-C2B domain and GST-Syt II-C2B were labeled by a
      stoichiometric amount of P-2-linked [3H]BZDC-IP6, the two polypeptides showed
      equivalent affinity for the photolabel. Although the CD spectrum of this 32-mer
      at two pH values showed a random coil, the photoaffinity analogue of IP6 appeared
      to induce a binding-compatible structure in the short peptide.

PMID- 9020138
TI  - Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a
      cytoskeleton-dependent signaling pathway initiated by ligation of integrin or
      antigen receptor on human B cells.
AB  - The Crk-associated substrate p130(Cas) (Cas) and the recently described human
      enhancer of filamentation 1 (HEF1) are two proteins with similar structure (64%
      amino acid homology), which are thought to act as "docking" molecules in
      intracellular signaling cascades. Both proteins contain an N-terminal Src
      homology (SH), three domain and a cluster of SH2 binding motifs. Here we show
      that ligation of either beta1 integrin or B cell antigen receptor (BCR) on human
      tonsillar B cells and B cell lines promoted tyrosine phosphorylation of HEF1. In
      contrast, Cas tyrosine phosphorylation was observed in certain B cell lines but
      not in tonsillar B cells, indicating a more general role for HEF1 in B cell
      signaling. Interestingly, pretreatment of tonsillar B cells with cytochalasin B
      dramatically reduced both integrin- and BCR-induced HEF1 phosphorylation,
      suggesting that some component of the BCR-mediated signaling pathway is closely
      linked with a cytoskeletal reorganization. Both HEF1 and Cas were found to
      complex with the related adhesion focal tyrosine kinase (RAFTK), and when
      tyrosine phosphorylated, with the adapter molecule CrkL. In addition, the two
      molecules were detected in p53/56(Lyn) immunoprecipitates, and Lyn kinase was
      found to specifically bind the C-terminal proline-rich sequence of Cas in an in
      vitro binding assay. These associations implicate HEF1 and Cas as important
      components in a cytoskeleton-linked signaling pathway initiated by ligation of
      beta1 integrin or BCR on human B cells.

PMID- 9020140
TI  - The conformational change responsible for AT1 receptor activation is dependent
      upon two juxtaposed asparagine residues on transmembrane helices III and VII.
AB  - A model of the angiotensin AT1 receptor and site-directed mutagenesis were used
      to identify key residues involved in ligand binding. Receptors were stably
      expressed in human embryonic kidney 293 cells, and their binding properties
      compared. Wild type receptors exhibited low and high affinity binding sites for
      peptides. Substitution of Asn111, situated in the third transmembrane helix,
      resulted in a significant alteration in ligand binding with only high affinity
      binding of the peptides, angiotensin II, angiotensin III, and [p-amino
      Phe6]angiotensin II and a marked loss in the binding affinity of the AT1 receptor
      selective non-peptide antagonist losartan. From our model it was apparent that
      Asn111 was in close spatial proximity to Asn295 in the seventh transmembrane
      helix. Substitution of Asn295, produced identical changes in the receptor's
      pharmacological profile. Furthermore, the Ser111AT1A and Ser295AT1A mutants did
      not require the association of a G-protein for high affinity agonist binding.
      Finally, the Ser295AT1A mutant maintained higher basal generation of inositol
      trisphosphate than the wild type, indicating constitutive activation. We propose
      that substitution of these residues causes the loss of an interaction between
      transmembrane helices III and VII, which allows the AT1 receptor to "relax" into
      its active conformation.

PMID- 9020141
TI  - 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine induces apoptosis in human
      neuroblastoma cells, SH-SY5Y, through a p53-dependent pathway.
AB  - We have studied the effect of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H
      7), a protein kinase inhibitor, on the regulation of apoptosis in the human
      neuroblastoma cell line, SH-SY5Y. H-7 (20-100 microM) induced apoptosis in these
      cells characterized by DNA fragmentation and chromatin condensation. Immunoblot
      analyses were performed with specific antibody against BCL-2, BCL-XS/L, BAX,
      JUNB, c-JUN, ICH-1L, c-FOS, RB, CDK-2, and p53. H-7 treatment did not
      significantly alter the level of these proteins with the exception of p53. H-7,
      but not staurosporine, caused a dramatic nuclear accumulation of p53. The
      kinetics of nuclear accumulation of p53 correlates well with the kinetics of
      induction of apoptosis. The effect of H-7 was further assessed in a group of
      human cell lines. Only cell lines harboring the wild-type p53 gene were
      responsive to the stimulatory effect of H-7 on nuclear accumulation of p53.
      Furthermore, cell lines carrying a mutated p53 gene were resistant to the
      cytotoxic effect of H-7. The ability of H-7 in mediating apoptosis in the SH-SY5Y
      line expressing a dominant negative mutant of p53 was significantly diminished.
      Taken together, these data strongly suggest that a p53-dependent mechanism
      contributes to the cytotoxicity of H-7 in human neuroblastoma cells.

PMID- 9020142
TI  - Three-dimensional structure of myelin basic protein. I. Reconstruction via
      angular reconstitution of randomly oriented single particles.
AB  - Myelin basic protein (MBP) plays an integral role in the structure and function
      of the myelin sheath. In humans and cattle, an 18.5-kDa isoform of MBP
      predominates and exists as a multitude of charge isomers resulting from extensive
      and varied post-translational modifications. We have purified the least modified
      isomer (named C1) of the 18.5-kDa isoform of MBP from fresh bovine brain and
      imaged this protein as negatively stained single particles adsorbed to a lipid
      monolayer. Under these conditions, MBP/C1 presented diverse projections whose
      relative orientations were determined using an iterative quaternion-assisted
      angular reconstitution scheme. In different buffers, one with a low salt and the
      other with a high salt concentration, the conformation of the protein was
      slightly different. In low salt buffer, the three-dimensional reconstruction,
      solved to a resolution of 4 nm, had an overall "C" shape of outer radius 5.5 nm,
      inner radius 3 nm, overall circumference 15 nm, and height 4.7 nm. The three
      dimensional reconstruction of the protein in high salt buffer, solved to a
      resolution of 2.8 nm, was essentially the same in terms of overall dimensions but
      had a somewhat more compact architecture. These results are the first structures
      achieved directly for this unusual macromolecule, which plays a key role in the
      development of multiple sclerosis.

PMID- 9020143
TI  - Three-dimensional structure of myelin basic protein. II. Molecular modeling and
      considerations of predicted structures in multiple sclerosis.
AB  - A computational model of myelin basic protein (MBP) has been constructed based on
      the premise of a phylogenetically conserved beta-sheet backbone and on electron
      microscopical three-dimensional reconstructions. Many residues subject to post
      translational modification (phosphorylation, methylation, or conversion of
      arginines to citrullines) were located in loop regions and thus accessible to
      modifying enzymes. The triproline segment (residues 99-101) is fully exposed on
      the back surface of the protein in a long crossover connection between two
      parallel beta-strands. The proximity of this region to the underlying beta-sheet
      suggests that post-translational modifications here might have potential
      synergistic effects on the entire structure. Post-translational modifications
      that lead to a reduced surface charge could result first in a weakened attachment
      to the myelin membrane rather than in a gross conformational change of the
      protein itself. Such mechanisms could be operative in demyelinating diseases such
      as multiple sclerosis.

PMID- 9020144
TI  - Compartmentalized activation of the high affinity immunoglobulin E receptor
      within membrane domains.
AB  - The earliest known step in the activation of the high affinity IgE receptor,
      FcepsilonRI, is the tyrosine phosphorylation of its beta and gamma subunits by
      the Src family tyrosine kinase, Lyn. We report here that aggregation-dependent
      association of FcepsilonRI with specialized regions of the plasma membrane
      precedes its tyrosine phosphorylation and appears necessary for this event.
      Tyrosine phosphorylation of beta and gamma occurs in intact cells only for
      FcepsilonRI that associate with these detergent-resistant membrane domains, which
      are enriched in active Lyn. Furthermore, efficient in vitro tyrosine
      phosphorylation of FcepsilonRI subunits occurs only for those associated with
      isolated domains. This association and in vitro phosphorylation are highly
      sensitive to low concentrations of detergent, suggesting that lipid-mediated
      interactions with Lyn are important in FcepsilonRI activation. Participation of
      membrane domains accounts for previously unexplained aspects of FcepsilonRI
      mediated signaling and may be relevant to signaling by other multichain immune
      receptors.

PMID- 9020145
TI  - Identification and characterization of a novel human matrix metalloproteinase
      with unique structural characteristics, chromosomal location, and tissue
      distribution.
AB  - We have cloned a novel member of the matrix metalloproteinase (MMP) family of
      proteins from a human liver cDNA library. The isolated cDNA contains an open
      reading frame coding for a polypeptide of 508 amino acids, which has been
      tentatively called MMP-19. This protein exhibits the domain structure
      characteristic of previously described MMPs, including a signal sequence, a
      prodomain with the cysteine residue essential for maintaining the latency of
      these enzymes, an activation locus with the zinc-binding site, and a COOH
      terminal fragment with sequence similarity to hemopexin. However, it lacks a
      series of structural features distinctive of the diverse MMP subclasses,
      including the Asp, Tyr, and Gly residues located close to the zinc-binding site
      in collagenases, the fibronectin-like domain of gelatinases, the transmembrane
      domain of membrane-type (MT) MMPs, and the furin-activation sequence common to
      stromelysin-3 and MT-MMPs. In addition, the 9-residue insertion rich in
      hydrophobic amino acids present at the hinge region in stromelysins is replaced
      in MMP-19 by a longer insertion very rich in acidic residues. On the basis of
      these structural characteristics, we propose that MMP-19 does not belong to any
      of the previously defined MMP-subclasses and may represent the first member of a
      new MMP subfamily. Chromosomal location of the MMP-19 gene revealed that it maps
      to chromosome 12q14, which is also a unique location for any MMPs mapped to date.
      The cDNA encoding a full-length MMP-19 was expressed in Escherichia coli, and
      after purification and refolding, the recombinant protein was able to degrade
      synthetic substrates for MMPs. MMP-19 proteolytic activity was abolished by TIMP
      2 and EDTA, thus providing additional evidence that the isolated cDNA codes for
      an authentic MMP. Northern blot analysis of polyadenylated RNAs isolated from a
      variety of human tissues revealed that MMP-19 is mainly expressed in placenta,
      lung, pancreas, ovary, spleen, and intestine, suggesting that it may play a
      specialized role in these tissues.

PMID- 9020146
TI  - Nuclear factor interleukin 6 motifs mediate tissue-specific gene transcription in
      hypoxia.
AB  - Activation of transcription at the nuclear factor interleukin 6 (NF-IL-6) DNA
      binding motif modulates expression of multiple genes important in host adaptive
      and developmental mechanisms. Studies showing that hypoxia-induced transcription
      of IL-6 in cultured endothelial cells was due to transcriptional activation by
      the NF-IL-6 motif in the promoter (Yan, S.-F., Tritto, I., Pinsky, D., Liao, H.,
      Huang, J., Fuller, G., Brett, J., May, L., and Stern, D. (1995) J. Biol. Chem.
      270, 11463-11471) led us to prepare transgenic mice using 115- or 14-base pair
      regions of the promoter encompassing the NF-IL-6 site ligated to the lacZ
      reporter gene and the basal thymidine kinase promoter. On exposure to hypoxia or
      induction of ischemia, mice bearing either of the constructs showed prominent
      expression of the transgene in lung and cardiac vasculature and in the kidney but
      not in the liver (parenchyma or vasculature). In contrast, transgenic mice
      bearing a mutationally inactivated NF-IL-6 site showed no increase in transgene
      expression in hypoxia. Gel retardation assays revealed time-dependent, hypoxia
      enhanced nuclear binding activity for the NF-IL-6 site in nuclear extracts of the
      heart, lung, and kidney but not in the liver; the hypoxia-enhanced band
      disappeared on addition of antibody to C/EBPbeta-NF-IL-6. Consistent with the
      specificity of hypoxia-mediated activation of C/EBPbeta-NF-IL-6, gel retardation
      assays showed no change in the intensity of the hypoxia-enhanced gel shift band
      in the presence of excess unlabeled oligonucleotide probes or antibodies related
      to other transcription factors, including NFkappaB, AP1, cAMP response element
      binding protein, SP1, and hypoxia-inducible factor 1. These data indicate that
      the transcription factor NF-IL-6 is sensitive to environmental oxygen
      deprivation, and the tissue-specific pattern of gene expression suggests that
      local mechanisms have an important regulatory effect.

PMID- 9020147
TI  - Induction of heme oxygenase-1 expression in vascular smooth muscle cells. A link
      to endotoxic shock.
AB  - Endotoxic shock is a life-threatening consequence of severe Gram-negative
      infection characterized by vascular smooth muscle cell relaxation and severe
      hypotension. The production of nitric oxide (NO), through the inducible NO
      synthase pathway, has been implicated as a major contributor in this process. We
      now demonstrate that heme oxygenase (HO), an enzyme that generates carbon
      monoxide (CO) in the course of heme metabolism, may also be involved in the
      hemodynamic compromise of endotoxic shock. Inducible HO (HO-1) mRNA levels are
      dramatically increased in aortic tissue from rats receiving endotoxin, and this
      increase in vascular HO-1 message is associated with an 8.9-fold increase in HO
      enzyme activity in vivo. Immunocytochemical staining localizes an increase in HO
      1 protein within smooth muscle cells of both large (aorta) and small (arterioles)
      blood vessels. Furthermore, zinc protoporphyrin IX, an inhibitor of HO activity,
      abrogates endotoxin-induced hypotension in rats. Studies performed in rat
      vascular smooth muscle cells in vitro show that the induction of HO-1 mRNA is
      regulated at the level of gene transcription, and this induction is independent
      of NO production. Taken together, these studies suggest that the up-regulation of
      HO-1, and the subsequent production of CO, contributes to the reduction in
      vascular tone during endotoxic shock.

PMID- 9020148
TI  - On the convergent evolution of animal toxins. Conservation of a diad of
      functional residues in potassium channel-blocking toxins with unrelated
      structures.
AB  - BgK is a K+ channel-blocking toxin from the sea anemone Bunodosoma granulifera.
      It is a 37-residue protein that adopts a novel fold, as determined by NMR and
      modeling. An alanine-scanning-based analysis revealed the functional importance
      of five residues, which include a critical lysine and an aromatic residue
      separated by 6.6 +/- 1.0 A. The same diad is found in the three known homologous
      toxins from sea anemones. More strikingly, a similar functional diad is present
      in all K+ channel-blocking toxins from scorpions, although these toxins adopt a
      distinct scaffold. Moreover, the functional diads of potassium channel-blocking
      toxins from sea anemone and scorpions superimpose in the three-dimensional
      structures. Therefore, toxins that have unrelated structures but similar
      functions possess conserved key functional residues, organized in an identical
      topology, suggesting a convergent functional evolution for these small proteins.

PMID- 9020149
TI  - Differential expression and sequence-specific interaction of karyopherin alpha
      with nuclear localization sequences.
AB  - The process of nuclear protein transport requires the interaction of several
      different proteins, either directly or indirectly with nuclear localization or
      targeting sequences (NLS). Recently, a number of karyopherins alpha, or NLS
      binding proteins, have been identified. We have found that the karyopherins hSRP1
      and hSRP1alpha are differentially expressed in various leukocyte cell lines and
      could be induced in normal human peripheral blood lymphocytes. We show that the
      two karyopherins bind with varied specificities in a sequence specific manner to
      different NLSs and that the sequence specificity is modulated by other cytosolic
      proteins. There was a correlation between binding of karyopherins alpha to
      different NLSs and their ability to be imported into the nucleus. Taken together,
      these data provide evidence for multiple levels of control of the nuclear import
      process.

PMID- 9020150
TI  - Identification of sites in domain I of perlecan that regulate heparan sulfate
      synthesis.
AB  - Perlecan is primarily a heparan sulfate containing proteoglycan found in all
      basement membranes. Rotary shadowed images of perlecan show it to contain three
      glycosaminoglycan (GAG) side chains extending from one end of its core protein.
      Domain I is at the N terminus of perlecan and contains three closely spaced Ser
      Gly-Asp sequences that may serve in GAG attachment. We evaluated the serines in
      these three sequences for GAG attachment by preparing a cDNA construct encoding
      for the N-terminal half (domains I, II, and III) of perlecan and then a series of
      constructs containing deletions and mutations within domain I of the domain
      I/II/III construct, expressing these constructs in COS-7 cells, and then
      analyzing the recombinant product for GAG side chains and GAG type. The results
      showed that all three serine residues in the Ser-Gly-Asp sequences in domain I
      can accept both chondroitin and heparan sulfate side chains but that a cluster of
      acidic residues N-terminal to these sequences is the primary determinant
      responsible for targeting these sites for heparan sulfate. Furthermore, there are
      two elements that can enhance heparan sulfate synthesis at a targeted site: 1)
      the presence of a the SEA module in the C-terminal region of domain I and 2) the
      presence of multiple acceptors in close proximity. These results indicate that
      the proportion of heparan and chondroitin sulfate at any one site in domain I of
      perlecan is regulated by multiple factors.

PMID- 9020151
TI  - A molecular redox switch on p21(ras). Structural basis for the nitric oxide
      p21(ras) interaction.
AB  - We have identified the site of molecular interaction between nitric oxide (NO)
      and p21(ras) responsible for initiation of signal transduction. We found that
      p21(ras) was singly S-nitrosylated and localized this modification to a fragment
      of p21(ras) containing Cys118. A mutant form of p21(ras), in which Cys118 was
      changed to a serine residue and termed p21(ras)C118S, was not S-nitrosylated. NO
      related species stimulated guanine nucleotide exchange on wild-type p21(ras),
      resulting in an active form, but not on p21(ras)C118S. Furthermore, in contrast
      to parental Jurkat T cells, NO-related species did not stimulate mitogen
      activated protein kinase activity in cells transfected with p21(ras)C118S. These
      data indicate that Cys118 is a critical site of redox regulation of p21(ras), and
      S-nitrosylation of this residue triggers guanine nucleotide exchange and
      downstream signaling.

PMID- 9020152
TI  - Immunoglobulin binding protein (BiP) function is required to protect cells from
      endoplasmic reticulum stress but is not required for the secretion of selective
      proteins.
AB  - BiP/GRP78 is a lumenal stress protein of the endoplasmic reticulum (ER) that
      interacts with polypeptide folding intermediates transiting the secretory
      compartment. We have studied the secretion and the stress response in Chinese
      hamster ovary (CHO) cells that overexpress either wild-type immunoglobulin
      binding protein (BiP) or a BiP deletion molecule (residues 175-201) that can bind
      peptides and ATP but is defective in ATP hydrolysis and concomitant peptide
      release. Overexpressed wild-type BiP was localized to the ER and unique vesicles
      within the nucleus, whereas overexpressed ATPase-defective BiP was localized to
      the ER and cytoplasmic vesicles but was absent from the nucleus. Compared with
      wild-type CHO cells, overexpression of ATPase-defective BiP prevented secretion
      of factor VIII, a coagulation factor that extensively binds BiP in the lumen of
      the ER. Under these conditions factor VIII was stably associated with the ATPase
      defective BiP. In contrast, the secretion of monocyte/macrophage colony
      stimulating factor, a protein that is not detected in association with BiP, was
      not affected by overexpression of ATPase-defective BiP. These results show that
      BiP function is not required for secretion of some proteins and suggest that some
      proteins do not interact with BiP upon transport through the ER. The presence of
      unfolded protein in the ER induces transcription of BiP and also elicits a
      general inhibition of protein synthesis. Overexpression of wild-type BiP
      prevented the stress-mediated transcriptional induction of BiP in response to
      either calcium ionophore A23187 treatment or tunicamycin treatment. In contrast,
      overexpression of ATPase-defective BiP did not prevent the stress induction of
      BiP, showing that the ATPase activity is required to inhibit transcriptional
      induction. Overexpression of wild-type BiP, but not ATPase-defective BiP,
      increased survival of cells treated with A23187. The increased survival mediated
      by overexpressed wild-type BiP correlated with reduced translation inhibition in
      response to the stress condition. These results indicate that overexpressed BiP
      alleviated the stress in the ER to prevent BiP transcriptional induction and
      permit continued translation of cellular mRNAs.

PMID- 9020154
TI  - Characterization of mouse Rt6.1 NAD:arginine ADP-ribosyltransferase.
AB  - Rat RT6 proteins, and perhaps mouse Rt6, identify a set of immunoregulatory T
      lymphocytes. Rat RT6.1 (RT6.1) and rat RT6.2 (RT6. 2) are NAD glycohydrolases,
      which catalyze auto-ADP-ribosylation, but not ADP-ribosylation of exogenous
      proteins. Mouse Rt6.1 (mRt6.1) also catalyzes auto-ADP-ribosylation. The activity
      of mouse cytotoxic T lymphocytes is reportedly inhibited by ADP-ribosylation of
      surface proteins, raising the possibility that mRt6 may participate in this
      process. The reactions catalyzed by mRt6, would, however, need to be more diverse
      than those of the rat homologues and include the ADP-ribosylation of acceptors
      other than itself. To test this hypothesis, mRt6.1 and rat RT6.2 were synthesized
      in Sf9 insect cells and rat mammary adenocarcinoma (NMU) cells. mRt6.1, but not
      rat RT6.2, catalyzed the ADP-ribosylation of guanidino-containing compounds (e.g.
      agmatine). Unlike RT6.2, mRt6.1 was a weak NAD glycohydrolase. In the presence of
      agmatine, however, the ratio of [adenine-14C]ADP-ribosylagmatine formation from
      [adenine-14C]NAD to [carbonyl-14C]nicotinamide formation from [carbonyl-14C]NAD
      was approximately 1.0, demonstrating that mRt6.1 is primarily a transferase. ADP
      ribosylarginine hydrolase, which preferentially hydrolyzes the alpha-anomer of
      ADP-ribosylarginine, released [U-14C]arginine from ADP-ribosyl[U-14C]arginine
      synthesized by mRT6.1, consistent with the conclusion that mRt6.1 catalyzes a
      stereospecific Sn2-like reaction. Thus, mRt6.1 is an NAD:arginine ADP
      ribosyltransferase capable of catalyzing a multiple turnover, stereospecific Sn2
      like reaction.

PMID- 9020153
TI  - Induction of Galphaq-specific antisense RNA in vivo causes increased body mass
      and hyperadiposity.
AB  - Transgenic BDF-1 mice harboring an inducible, tissue-specific transgene for RNA
      antisense to Galphaq provide a model in which to study a loss-of-function mutant
      of Galphaq in vivo. Galphaq deficiency induced in liver and white adipose tissue
      at birth produced increased body mass and hyperadiposity within 5 weeks of birth
      that persisted throughout adult life. Galphaq-deficient adipocytes display
      reduced lipolytic responses, shown to reflect a newly discovered, alpha1
      adrenergic regulation of lipolysis. This alpha1-adrenergic response via
      phosphoinositide hydrolysis and activation of protein kinase C is lacking in the
      Galphaq loss-of-function mutants in vivo and provides a basis for the increased
      fat accumulation.

PMID- 9020155
TI  - Developmental changes in hemocyanin expression in the Dungeness crab, Cancer
      magister.
AB  - The copper-based respiratory protein hemocyanin undergoes a developmental shift
      in subunit composition and function analogous to that seen in many hemoglobins.
      We studied hemocyanin gene expression in the Dungeness crab (Cancer magister) by
      Northern blot analysis. Animals were raised under controlled conditions, and
      total RNA was isolated from 13 developmental stages as well as from six tissue
      types in the adult animal. RNA was run on formaldehyde-agarose gels, blotted onto
      nylon membranes, and probed with 32P-labeled cDNA probes specific for C. magister
      adult hemocyanin. Results indicate that adult hemocyanin biosynthesis occurs in
      hepatopancreas tissue only. Analysis of developmental stages shows that
      expression of adult-type hemocyanin, as indicated by the appearance of hemocyanin
      subunit 6 mRNA, begins during the sixth juvenile instar.

PMID- 9020156
TI  - Platelet-derived growth factor (PDGF)-induced Ca2+ signaling in the CG4
      oligodendroglial cell line and in transformed oligodendrocytes expressing the
      beta-PDGF receptor.
AB  - Ca2+ signaling induced by platelet-derived growth factor (PDGF) was investigated
      in the oligodendroglial cell lines CG4 and CEINGE clone 3, using fura-2
      microfluorimetry and video imaging. CEINGE cl3 cells, immortalized with polyoma
      middle T antigen, were found to uniformly express the polyoma middle T antigen
      protein as well as 2',3'-cyclic nucleotide 3'-phosphodiesterase, a specific
      marker for oligodendroglia. PDGF-BB induced both oscillatory and non-oscillatory
      Ca2+ responses in CEINGE cl3 cells as well as in CG4 cells, grown either as O-2A
      progenitors or differentiated oligodendrocytes. However, in CG4 cells the
      percentage of oscillatory Ca2+ responses was higher than that observed in CEINGE
      cl3 cells. In contrast, oscillatory Ca2+ responses were not observed in PC-12
      cells transfected with beta-PDGF receptor (PDGFR) or in NIH 3T3 fibroblasts. CG4
      cells expressed only the alpha-PDGFR, whereas CEINGE cl3 cells expressed both
      alpha and beta isoforms. When CEINGE cl3 cells were exposed to PDGF-AA, which
      binds only to the alpha-PDGFR, the percentage of oscillatory Ca2+ responses was
      higher than that observed after PDGF-BB stimulation. We previously reported that
      block of the enzyme sphingosine kinase, and a consequent increase in
      intracellular sphingosine levels in CEINGE cl3 cells caused an increase in the
      percentage of oscillatory Ca2+ responses induced by PDGF-BB. However, in CG4
      cells block of sphingosine kinase did not increase the oscillatory Ca2+ response
      elicited by PDGF-BB, although the addition of exogenous sphingosine induced an
      oscillatory Ca2+ response in 77% of cells studied. We hypothesize that the alpha
      PDGFR is less effective than the beta-PDGFR in stimulating the activity of
      sphingosine kinase. The results also suggest that alpha- and beta-PDGFRs may
      differently regulate sphingolipid metabolism.

PMID- 9020157
TI  - Interference with DNA methyltransferase activity and genome methylation during F9
      teratocarcinoma stem cell differentiation induced by polyamine depletion.
AB  - When ornithine decarboxylase, the initial and highly regulated enzyme in
      polyamine biosynthesis, is irreversibly inactivated by alpha
      difluoromethylornithine, F9 teratocarcinoma stem cells are depleted of putrescine
      and spermidine and as a result differentiate into a cell type which
      phenotypically resembles the parietal endoderm cells of the early mouse embryo.
      Simultaneously the level of decarboxylated S-adenosylmethionine (dcAdoMet), the
      aminopropyl group donor in spermidine and spermine synthesis, increases
      dramatically, as the aminopropyl group acceptor molecules (putrescine and
      spermidine) become limiting. When this excessive accumulation of dcAdoMet is
      prevented by specific inhibition of the AdoMet decarboxylase activity, the
      differentiative effect is counteracted, despite the fact that the extent of
      polyamine depletion remains almost identical. Therefore, it may be concluded that
      dcAdoMet plays an important role in the induction of differentiation. Moreover,
      this key metabolite acts as a competitive inhibitor of DNA methyltransferase and
      is therefore capable of interfering with the maintenance methylation of newly
      replicated DNA. During the course of F9 cell differentiation, the highly
      methylated genome is gradually demethylated, and its pattern of gene expression
      is changed. Our present findings, that the DNA remains highly methylated and that
      the differentiative process is counteracted when the build-up of dcAdoMet is
      prevented, provide strong evidence for a causative relation between the level of
      dcAdoMet and the state of DNA methylation as well as cell differentiation.

PMID- 9020158
TI  - Regulation of tissue factor initiated thrombin generation by the stoichiometric
      inhibitors tissue factor pathway inhibitor, antithrombin-III, and heparin
      cofactor-II.
AB  - The effects of the stoichiometric inhibitors tissue factor pathway inhibitor
      (TFPI), antithrombin-III (AT-III) and heparin cofactor-II (HC-II) on thrombin
      generation were evaluated in a reaction system composed of coagulation factors
      VIIa, X, IX, VIII, and V and prothrombin initiated by tissue factor (TF) and
      phospholipids. Initiation of the reaction in the absence of inhibitors resulted
      in explosive thrombin generation for factor VIIa.TF concentrations varying from
      100 to 0.25 pM with the lag time or initiation phase of thrombin generation
      increasing from 0 to 180 s with decreasing factor VIIa.TF concentrations. During
      the propagation phase, prothrombin is quantitatively activated to 1.4 micro;M
      alpha-thrombin. At normal plasma concentration (2.5 nM) full-length recombinant
      TFPI prolonged the initiation phase of thrombin generation 2-fold, and the rate
      of thrombin generation in the propagation phase of the reaction was 25-50% that
      of the uninhibited reaction when the reaction was initiated with 1.25-20 pM
      factor VIIa.TF. Inhibition of the reaction by TFPI is associated with a delay in
      factor V activation. In the presence of TFPI no explosive thrombin generation was
      observed when factor VIII was omitted from reactions initiated by factor VIIa.TF
      concentrations </=20 pM. This indicates that in the presence of TFPI the factor
      IXa.factor VIIIa pathway becomes essential at low factor VIIa.TF concentrations.
      In the reconstituted system, AT-III (3.4 micro;M) did not prolong the initiation
      phase of thrombin generation when the reaction was initiated with 1.25 pM factor
      VIIa.TF, nor did AT-III delay factor V activation. The rate of thrombin formation
      in the presence of AT-III was reduced to 30% that of the uninhibited reaction,
      and the alpha-thrombin formed was rapidly inhibited subsequent to its generation.
      The addition of HC-II alone at its physiological concentration (1.38 micro;M) to
      the procoagulant mixture did not alter the rate or extent of thrombin generation.
      Subsequently, the thrombin formed was slowly inhibited by HC-II. The slow
      inactivation of thrombin by HC-II does not contribute to thrombin inhibition in
      the presence of AT-III. In contrast, the combination of physiological levels of
      AT-III and TFPI inhibited explosive thrombin generation initiated by 1.25 pM
      factor VIIa.TF completely. The absence of prothrombin consumption indicated that
      the combination of TFPI and AT-III is able to prevent the formation of
      prothrombinase activity at low factor VIIa.TF concentrations. The data indicate
      that TFPI potentiates the action of AT-III by decreasing the rate of formation
      and thus the amount of catalyst formed in the reaction, enabling AT-III to
      effectively scavenge the limited traces of factor IXa and factor Xa formed in the
      presence of TFPI. The initiation of thrombin generation by increasing factor
      VIIa.TF concentrations in the presence of physiological concentrations of TFPI
      and AT-III showed dramatic changes in the maximal rates of thrombin generation
      over small changes in initiator concentration. These data demonstrate that
      significant thrombin generation becomes a "threshold-limited" event with regard
      to the initiating factor VIIa.TF concentration in the presence of TFPI and AT
      III.

PMID- 9020159
TI  - Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine
      kinases.
AB  - It has previously been shown that maximal activation of Raf-1 is produced by
      synergistic signals from oncogenic Ras and activated tyrosine kinases. This
      synergy arises because Ras-GTP translocates Raf-1 to the plasma membrane where it
      becomes phosphorylated on tyrosine residues 340 and 341 by membrane-bound
      tyrosine kinases (Marais, R., Light, Y., Paterson, H. F., and Marshall, C. J.
      (1995) EMBO J. 14, 3136-3145). We have examined whether the other two members of
      the Raf family, A-Raf and B-Raf, are regulated in a similar way to Raf-1. A-Raf
      behaves like Raf-1, being weakly activated by oncogenic Ras more strongly
      activated by oncogenic Src, and these signals synergize to give maximal
      activation. B-Raf by contrast is strongly activated by oncogenic Ras alone and is
      not activated by oncogenic Src. These results show that maximal activation of B
      Raf merely requires signals that generate Ras-GTP, whereas activation of Raf-1
      and A-Raf requires Ras-GTP together with signals that lead to their tyrosine
      phosphorylation. B-Raf may therefore be the primary target of oncogenic Ras.

PMID- 9020160
TI  - Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol
      4-kinase.
AB  - Phosphatidylinositol (PtdIns) 4-kinases catalyze the synthesis of PtdIns-4-P, the
      immediate precursor of PtdIns-4,5-P2. Here we report the cloning of a novel,
      ubiquitously expressed PtdIns 4-kinase (PI4Kbeta). The 2.4-kilobase pair cDNA
      encodes a putative translation product of 801 amino acids which shows greatest
      homology to the yeast PIK1 gene. The recombinant protein exhibits lipid kinase
      activity when expressed in Escherichia coli, and specific antibodies recognize a
      110-kDa PtdIns 4-kinase in cell lysates. The biochemical properties of PI4Kbeta
      are characteristic of a type III enzyme. Interestingly, both recombinant PI4Kbeta
      and the endogenous protein are inhibited by 150 nM wortmannin, suggesting that we
      have cloned the previously described PtdIns 4-kinase that is responsible for
      regulating the synthesis of agonist-sensitive pools of polyphosphoinositides
      (Nakanishi, S., Catt, J. K., and Balla, T. (1995) Proc. Natl. Acad. Sci. U. S. A.
      92, 5317-5321).

PMID- 9020161
TI  - Role of the small GTPase Rab7 in the late endocytic pathway.
AB  - Rab7 is a small GTPase localized to the late endosomal compartment. Its function
      was investigated by overexpressing dominant negative or constitutively active
      mutants in BHK-21 cells. The effects of such overexpression on the
      internalization and/or degradation of different endocytic markers and on the
      morphology of the late endosomal compartment were analyzed. We observed a marked
      inhibition of the degradation of 125I-low density lipoproteins in cells
      transfected with the Rab7 dominant negative mutants while the rate of
      internalization was not affected. Moreover in these cells there was an
      accumulation of many small vesicles scattered throughout the cytoplasm. In
      contrast, overexpression of the activating mutants led to the appearance of
      atypically large endocytic structures and caused a dramatic change in the
      distribution of the cation-independent mannose 6-phosphate receptor. Our data
      indicate that the Rab7 protein in mammalian cells is present on a late endosomal
      compartment much larger than the compartment labeled by the cation-independent
      mannose 6-phosphate receptor. Rab7 also appears to play a fundamental role in
      controlling late endocytic membrane traffic.

PMID- 9020162
TI  - Mutational analysis of the properties of caveolin-1. A novel role for the C
      terminal domain in mediating homo-typic caveolin-caveolin interactions.
AB  - Caveolin is a principal structural component of caveolae membranes in vivo.
      Recently, a family of caveolin-related proteins has been identified; caveolin has
      been retermed caveolin-1. Caveolin family members share three characteristic
      properties: (i) detergent insolubility at low temperatures; (ii) self
      oligomerization; and (iii) incorporation into low density Triton-insoluble
      fractions enriched in caveolae membranes. Here, we have used a deletion
      mutagenesis approach as a first step toward understanding which regions of
      caveolin-1 contribute to its unusual properties. Two caveolin-1 deletion mutants
      were created that lack either the C-terminal domain (Cav-1DeltaC) or the N
      terminal domain (Cav-1DeltaN); these mutants were compared with the behavior of
      full-length caveolin-1 (Cav-1FL) expressed in parallel. Our results show that the
      N-terminal domain and membrane spanning segment are sufficient to form high
      molecular mass oligomers of caveolin-1. However, a complete caveolin-1 molecule
      is required for conveying detergent insolubility and incorporation into low
      density Triton-insoluble complexes. These data indicate that homo-oligomerization
      and an intact transmembrane are not sufficient to confer detergent insolubility,
      suggesting an unknown role for the C-terminal domain in this process. To better
      understand the role of the C-terminal domain, this region of caveolin-1 (residues
      135-178) was expressed as a glutathione S-transferase fusion protein in
      Escherichia coli. Purified recombinant glutathione S-transferase-C-Cav-1 was
      found to stably interact with full-length caveolin-1 but not with the two
      caveolin-1 deletion mutants. These results suggest that the C-terminal domain
      interacts with both the N-terminal and C-terminal domains of an adjacent caveolin
      1 homo-oligomer. This appears to be a specific homo-typic interaction, because
      the C-terminal domain of caveolin-1 failed to interact with full-length forms of
      caveolin-2 and caveolin-3. Homo-typic interaction of the C-terminal domain with
      an adjacent homo-oligomer could provide a mechanism for clustering caveolin-1
      homo-oligomers while excluding other caveolin family members. This type of
      lateral segregation event could promote caveolae membrane formation and
      contribute to the detergent insolubility of caveolins-1, -2, and -3.

PMID- 9020163
TI  - Physicochemical characterization of the nucleational core of matrix vesicles.
AB  - While previous studies revealed that matrix vesicles (MV) contain a nucleational
      core (NC) that converts to apatite when incubated with synthetic cartilage lymph,
      the initial mineral phase present in MV is not well characterized. This study
      explored the physicochemical nature of this Ca2+ and Pi-rich NC. MV, isolated
      from growth plate cartilage, were analyzed directly by solid-state 31P NMR, or
      incubated with hydrazine or NaOCl to remove organic constituents. Other samples
      of MV were subjected to sequential treatments with enzymes, salt solutions, and
      detergents to expose the NC. We examined the NC using transmission electron
      microscopy, energy-dispersive analysis with x-rays, and electron and x-ray
      diffraction, Fourier transform-infrared spectroscopy, high performance thin-layer
      chromatographic analysis, and SDS-polyacrylamide gel electrophoresis. We found
      that most of the MV proteins and lipids could be removed without destroying the
      NC; however, NaOCl treatment annihilated its activity. SDS-polyacrylamide gel
      electrophoresis showed that annexin V, a phosphatidylserine (PS)-dependent Ca2+
      binding protein, was the major protein in the NC; high performance thin-layer
      chromatographic analysis revealed that the detergents removed the majority of the
      polar lipids, but left significant free cholesterol and fatty acids, and small
      but critical amounts of PS. Transmission electron microscopy showed that the NC
      was composed of clusters of approximately 1.0 nm subunits, which energy
      dispersive analysis with x-rays revealed contained Ca and Pi with a Ca/P ratio of
      1.06 +/- 0. 01. Electron diffraction, x-ray diffraction, and Fourier transform
      infrared analysis all indicated that the NC was noncrystalline. 1H-Cross
      polarization 31P NMR indicated that the solid phase of MV was an HPO42--rich
      mixture of amorphous calcium phosphate and a complex of PS, Ca2+, and Pi. Taken
      together, our findings indicate that the NC of MV is composed of an acid
      phosphate-rich amorphous calcium phosphate intermixed with PS-Ca2+-Pi, annexin V,
      and other proteins and lipids.

PMID- 9020164
TI  - The effects of severely decreased hydrophobicity in a subdomain 3/4 loop on the
      dynamics and stability of yeast G-actin.
AB  - The hydrophobicity of the subdomain 3/4 hydrophobic loop (262-274) has been
      implicated to be essential for actin's function. We previously showed (Kuang, B.,
      and Rubenstein, P. A. (1997) J. Biol. Chem. 272, 1237-1247) that a mutant yeast
      actin (V266G/L267G) with markedly decreased hydrophobicity in this loop conferred
      severe cold sensitivity to its polymerization. Here we further tested the
      mutational effect on the conformation and function of G-actin. This GG mutation
      caused no significant changes in overall secondary structure or in the
      microenvironment around actin's tryptophan residues, nor did it alter the
      dissociation constant of G-actin for ATP. However, it lowers the intrinsic ATPase
      activity and the melting temperature for Mg-GG actin from 51 to 33 degrees C and
      transforms the conformation of subdomain 2 and the central cleft of G-actin into
      an F-monomer-like structure. The results suggest that the hydrophobic plug may
      not only play a role in actin filament stabilization but also may be important
      for controlling the stability of G-actin and for promoting the conformational
      change of the monomer needed for addition to a growing actin filament.

PMID- 9020165
TI  - Functionally distinct double-stranded RNA-binding domains associated with
      alternative splice site variants of the interferon-inducible double-stranded RNA
      specific adenosine deaminase.
AB  - The double-stranded RNA-specific adenosine deaminase (ADAR) is an interferon
      inducible RNA-editing enzyme implicated in the site-selective deamination of
      adenosine to inosine in viral RNAs and cellular pre-mRNAs. We have isolated and
      characterized human genomic clones of the ADAR gene and cDNA clones encoding
      splice site variants of the ADAR protein. Southern blot and sequence analyses
      revealed that the gene spans about 30 kilobase pairs and consists of 15 exons.
      The codon phasing of the splice site junctions of exons 3, 5, and 7 that encode
      the three copies of the highly conserved RNA-binding R-motif (RI, RII, and RIII)
      was exactly conserved and identical to those R-motif exons of the interferon
      inducible RNA-dependent protein kinase. Alternative splice site variants of the
      1226-amino acid ADAR-a protein, designated b and c, were identified that differed
      in exons 6 and 7. ADAR-b was a 5'-splice site variant that possessed a 26-amino
      acid deletion within exon 7; ADAR-c was a 3'-splice site variant that possessed
      an additional 19-amino acid deletion within exon 6. The wild-type ADAR-a, -b, and
      -c proteins all possessed comparable double-stranded RNA-specific adenosine
      deaminase activity. However, mutational analysis of the R-motifs revealed that
      the exon 6 and 7 deletions of ADAR-b and -c variants altered the functional
      importance of each of the three R-motifs.

PMID- 9020166
TI  - Molecular cloning, developmental expression, and phosphorylation of ribosomal
      protein S6 in the endocrine gland responsible for insect molting.
AB  - Phosphorylation of ribosomal protein S6 is requisite for prothoracicotropic
      hormone (PTTH)-stimulated specific protein synthesis and subsequent
      ecdysteroidogenesis in the prothoracic glands of the tobacco hornworm, Manduca
      sexta. To better understand the role of S6 in regulating ecdysteroidogenesis, S6
      cDNA was isolated from a Manduca prothoracic gland cDNA library and sequenced.
      The deduced protein is comprised of 253 amino acids, has a molecular weight of
      29,038, and contains four copies of a 10-amino acid motif defining potential DNA
      binding sites. This Manduca S6 possesses a consensus recognition sequence for the
      p70(s6k) binding domain as well as six seryl residues at the carboxyl-terminal
      sequence of 17 amino acids. Phosphoamino acid analysis revealed that the
      phosphorylation of Manduca prothoracic gland S6 is limited exclusively to serine
      residues. Although alterations in the quantity of S6 mRNA throughout the last
      larval instar and early pupal-adult development were not well correlated with the
      hemolymph ecdysteroid titer, developmental expression and phosphorylation of S6
      were temporally correlated with PTTH release and the hemolymph ecdysteroid titer.
      These data provide additional evidence that S6 phosphorylation is a critical
      element in the transduction pathway leading to PTTH-stimulated
      ecdysteroidogenesis.

PMID- 9020167
TI  - Oncogenic point mutations induce altered conformation, redox sensitivity, and DNA
      binding in the minimal DNA binding domain of avian myeloblastosis virus v-Myb.
AB  - c-Myb is the founder member of a class of transcription factors with tryptophan
      rich repeats responsible for DNA binding. Activated oncogenic forms of Myb are
      encoded by the avian retroviruses, avian myeloblastosis virus (AMV) and E26. AMV
      v-Myb encodes a truncated protein with 11 point mutations relative to c-Myb. The
      mutations in the DNA binding domain (DBD) were reported to impose distinct
      phenotypes of differentiation on transformed myeloid cells (Introna, M., Golay,
      J., Frampton, J., Nakano, T., Ness, S. A., and Graf, T. (1990) Cell 63, 1287
      1297). The molecular mechanism operating has remained elusive since no change in
      sequence specificity has been found. We introduced AMV-specific point mutations
      in the minimal DBD of chicken c-Myb and studied their effect on structure and
      function of the purified protein. Fluorescence emission spectra and fluorescence
      quenching experiments showed that the AMV-specific point mutations had a
      significant effect on the conformation of the DBD, giving rise to a more compact
      structure, a change that was accompanied by a reduced sensitivity toward cysteine
      specific alkylation and oxidation. The DNA binding properties were also altered
      by the AMV-specific point mutations, leading to protein-DNA complexes with highly
      reduced stability. This reduction in stability was, however, more severe with
      certain subtypes of binding sequences than with others. This differential
      behavior was also observed in an in vivo model system where DBD-VP16 fusions were
      coexpressed with various reporters. These findings imply that different subsets
      of Myb-responsive promoters may react differentially toward the AMV-specific
      mutations, a phenomenon that could contribute to the altered patterns of gene
      expression induced by the AMV v-Myb relative to wild type c-Myb.

PMID- 9020168
TI  - Molecular characterization of GCV3, the Saccharomyces cerevisiae gene coding for
      the glycine cleavage system hydrogen carrier protein.
AB  - YAL044, a gene on the left arm of Saccharomyces cerevisiae chromosome one, is
      shown to code for the H-protein subunit of the multienzyme glycine cleavage
      system. The gene designation has therefore been changed to GCV3, reflecting its
      role in the glycine cleavage system. GCV3 encodes a 177-residue protein with a
      putative mitochondrial targeting signal at its amino terminus. Targeted gene
      replacement shows that GCV3 is not required for growth on minimal medium;
      however, it is essential when glycine serves as the sole nitrogen source. Studies
      of GCV3 expression revealed that it is highly regulated. Supplementation of
      minimal medium with glycine, the glycine cleavage system's substrate, induced
      expression at least 30-fold. In contrast, and consistent with the cleavage of
      glycine providing activated single-carbon units, the addition of the metabolic
      end products that require activated single-carbon units repressed expression
      about 10-fold. Finally, like many amino acid biosynthetic genes, GCV3 is subject
      to regulation by the general amino acid control system.

PMID- 9020169
TI  - Two murine homologs of the Drosophila single-minded protein that interact with
      the mouse aryl hydrocarbon receptor nuclear translocator protein.
AB  - Drosophila single-minded, which acts as a positive master gene regulator in
      central nervous system midline formation in Drosophila, its two mouse homologs
      SIM1 and SIM2, and the mammalian aryl hydrocarbon receptor (AHR) and aryl
      hydrocarbon receptor nuclear translocator (ARNT) proteins are members of the
      basic-helix-loop-helix.PAS family of transcription factors. In the yeast two
      hybrid system, we demonstrate strong constitutive interaction of ARNT with SIM1
      and SIM2 and fully ligand-dependent interaction of ARNT with AHR. Both the helix
      loop-helix and the PAS regions of SIM1 and of ARNT are required for efficient
      heterodimerization. SIM1 and SIM2 do not form homodimers, and they do not
      interact with AHR. We also failed to detect homodimerization of ARNT. The
      interaction of ARNT with SIM1 was confirmed with in vitro synthesized proteins.
      Like AHR, in vitro synthesized SIM1 associates with the 90-kDa heat shock
      protein. SIM1 inhibits binding of the AHR.ARNT dimer to the xenobiotic response
      element in vitro. Introduction of SIM1 into hepatoma cells inhibits
      transcriptional transactivation by the endogenous AHR.ARNT dimer. The mouse SIM1.
      ARNT dimer binds only weakly to a proposed DNA target for the Drosophila SIM.ARNT
      dimer. In adult mice mRNA for SIM1 was expressed in lung, skeletal muscle, and
      kidney, whereas the mRNA for SIM2 was found in the latter two. ARNT is also
      expressed in these organs. Thus mouse SIM1 and SIM2 are novel heterodimerization
      partners for ARNT in vitro, and they may function both as positive and negative
      transcriptional regulators in vivo, during embryogenesis and in the adult
      organism.

PMID- 9020170
TI  - Regulation of the human inosine monophosphate dehydrogenase type I gene.
      Utilization of alternative promoters.
AB  - Catalysis of guanine nucleotide formation from IMP in the de novo purine
      synthetic pathway is carried out by two isoforms of the enzyme inosine
      monophosphate dehydrogenase (IMPDH) that are catalytically indistinguishable but
      are encoded by separate genes. In order to assess the potential for cell type
      specific expression of IMPDH activity, we have characterized the IMPDH type I
      gene and identified three major RNA transcripts that are differentially expressed
      from three different promoters. A 4.0-kilobase pair (kb) mRNA containing 1.3 kb
      of 5'-untranslated region is expressed in activated peripheral blood lymphocytes
      and to a far lesser extent in cultured tumor cell lines. The P1 promoter that
      regulates the transcription of this mRNA has a high degree of sequence identity
      to an Alu repetitive sequence. A transcript of 2.7 kb is found in a subset of the
      tumor cell lines examined, whereas a 2.5-kb mRNA species is universally expressed
      and is the prevalent mRNA in most cell lines and tissues. The relative strengths
      of the three promoter regions and the effects of variable extents of 5'-flanking
      sequence on the P3 promoter differ in Jurkat T, as compared with Raji B lymphoid
      cell lines, demonstrating a complex cell type-specific transcriptional regulation
      of IMPDH type I gene expression.

PMID- 9020171
TI  - Characterization of the Bradyrhizobium japonicum CycY protein, a membrane
      anchored periplasmic thioredoxin that may play a role as a reductant in the
      biogenesis of c-type cytochromes.
AB  - A new member of membrane-anchored periplasmic thioredoxin-like proteins was
      identified in Bradyrhizobium japonicum. It is the product of cycY, the last gene
      in a cluster of cytochrome c biogenesis genes. Mutational analysis revealed that
      cycY is essential for the biosynthesis of all c-type cytochromes in this
      bacterium. The CycY protein was shown to be exported to the periplasm by its N
      terminal signal sequence-like domain. Results from Western blot analyses of
      membrane and soluble fractions indicated that the CycY protein remains bound to
      the membrane. A soluble version of the protein devoid of its N-terminal membrane
      anchor (CycY*) was expressed in Escherichia coli and purified to homogeneity from
      the periplasmic fraction. The protein showed redox reactivity and properties
      similar to other thioredoxins such as fluorescence quenching in the oxidized
      form. Its equilibrium constant with glutathione was determined to be 168 mM, from
      which a standard redox potential of -0.217 V was calculated, suggesting that CycY
      might act as a reductant in the otherwise oxidative environment of the periplasm.
      This is in agreement with our hypothesis that CycY is required, directly or
      indirectly, for the reduction of the heme-binding site cysteines in the CXXCH
      motif of c-type apocytochromes before heme attachment occurs.

PMID- 9020172
TI  - Purification and characterization of qTBP42, a new single-stranded and quadruplex
      telomeric DNA-binding protein from rat hepatocytes.
AB  - Telomeres of vertebrate chromosomes terminate with a short 5'-d(TTAGGG)-3' single
      stranded overhang that can form in vitro tetrahelical structures. Here we
      describe a new protein from rat hepatocyte nuclei designated quadruplex telomere
      binding protein 42 (qTBP42) that tightly binds 5'-d(TTAGGG)n-3' and 5'-d(CCCTAA)n
      3' single-stranded and tetraplex forms of 5'd(TTAGGG)n-3'. The thermostable
      qTBP42 was isolated from boiled nuclear extracts and purified to near homogeneity
      by successive steps of column chromatography on DEAE-cellulose, phosphocellulose,
      and phenyl-Sepharose. A subunit molecular size of 42.0 +/- 2.0 kDa was determined
      for qTBP42 by Southwestern blotting and SDS-polyacrylamide gel electrophoresis of
      the protein and its UV cross-linked complex with labeled telomeric DNA. A native
      size of 53. 5 +/- 0.9 kDa, estimated by Superdex copyright 200 gel filtration,
      suggests that qTBP42 is a monomeric protein. Sequences of five tryptic peptides
      of qTBP42 contained motifs shared by a mammalian CArG box-binding protein, hnRNP
      A/B, hnRNP C, and a human single-stranded telomeric DNA-binding protein.
      Complexes of qTBP42 with each complementary strand of telomeric DNA and with
      quadruplex forms of the guanine-rich strand had 3.7-14.6 nM dissociation
      constants, Kd, whereas complexes with double-stranded telomeric DNA had up to 100
      fold higher Kd values. By associating with tetraplex and single-stranded
      telomeric DNA, qTBP42 increased their heat stability and resistance to digestion
      by micrococcal nuclease.

PMID- 9020173
TI  - Accumulation of E2F-4.DP-1 DNA binding complexes correlates with induction of
      dhfr gene expression during the G1 to S phase transition.
AB  - Previously genomic DNase I footprinting showed changes in protein binding to two
      overlapping E2F sites correlates with activation of dhfr gene expression at the
      G1/S boundary of the Chinese hamster cell cycle (Wells, J., Held, P., Illenye,
      S., and Heintz, N. H. (1996) Mol. Cell. Biol. 16, 634-647). Here gel mobility and
      antibody supershift assays were used to relate changes in the components of E2F
      DNA binding complexes in cell extracts to repression and induction of dhfr gene
      expression. In extracts from log phase cells, E2F complexes contained
      predominantly E2F-4 and E2F-2 in association with DP-1, and DNA binding assays
      showed complexes containing E2F-2 preferentially interact with only one of the
      two overlapping E2F sites. In serum starvation-stimulation experiments, arrest in
      G1 by low serum was accompanied by decreased levels of dhfr mRNA and the
      appearance of an E2F-4.DP-1.p130 complex. After serum stimulation, induction of
      dhfr gene expression was preceded by loss of the p130 complex in mid G1 and
      coincided with marked increases in two free E2F.DP-1 complexes in late G1, one of
      which contained E2F-4 and a second which contained an unidentified E2F. We
      suggest activation of dhfr gene expression after serum stimulation requires at
      least two temporally distinct processes, relief of p130-mediated repression and
      subsequent activation of transcription by free E2F.

PMID- 9020174
TI  - Analysis of post-transcriptional regulation operating on transcription products
      of the tandemly linked Leishmania infantum hsp70 genes.
AB  - The genomic organization and expression of the hsp70 genes of Leishmania infantum
      were examined. In the cluster there are at least six copies of the hsp70 genes
      arranged in a head-to-tail tandem of 3. 8-kilobase repetition units. The hsp70
      gene copy (gene 6) located at the 3' end of the tandem has a 3'-untranslated
      region highly divergent in sequence relative to the 3'-untranslated region of the
      rest of hsp70 gene copies (genes 1-5). Nuclease S1 protection assays indicated
      that the steady-state level of the mRNAs derived from gene 6 is about 50-fold
      more abundant than the transcript level derived from genes 1-5. Nuclear run-on
      assays showed, however, that all hsp70 genes are transcribed at similar rates.
      Thus, it is likely that the differences in the steady-state levels of the
      transcripts from the hsp70 genes should be associated with variations in their
      processing or maturation rates. While the abundance of the mRNAs derived from
      hsp70 genes 1-5 is increased by heat shock, the hsp70 gene 6 mRNA level remains
      unaffected. Our data showed that ongoing protein synthesis is required for the
      maintenance of the heat inducement, depicting, thus, a post-transcriptional
      mechanism of positive regulation involving a labile protein factor that would be
      either induced or activated during heat shock.

PMID- 9020175
TI  - Association of tyrosine-phosphorylated c-Src with the cytoskeleton of
      hypertrophying myocardium.
AB  - Given the central position of the focal adhesion complex, both physically in
      coupling integrins to the interstitium and biochemically in providing an upstream
      site for anabolic signal generation, we asked whether the recruitment of non
      receptor tyrosine kinases to the cytoskeleton might be a mechanism whereby
      cellular loading could activate growth regulatory signals responsible for cardiac
      hypertrophy. Analysis revealed cytoskeletal association of c-Src, FAK, and beta3
      integrin, but no Fyn, in the pressure-overloaded right ventricle. This
      association was seen as early as 4 h after right ventricular pressure
      overloading, increased through 48 h, and reverted to normal in 1 week.
      Cytoskeletal binding of non-receptor tyrosine kinases was synchronous with
      tyrosine phosphorylation of several cytoskeletal proteins, including c-Src.
      Examination of cytoskeleton-bound c-Src revealed that a significant portion of
      the tyrosine phosphorylation was not at the Tyr-527 site and therefore presumably
      was at the Tyr-416 site. Thus, these studies strongly suggest that non-receptor
      tyrosine kinases, in particular c-Src, may play a critical role in hypertrophic
      growth regulation by their association with cytoskeletal structures, possibly via
      load activation of integrin-mediated signaling.

PMID- 9020176
TI  - Phosphorylation-dependent monoclonal Tau antibodies do not reliably report
      phosphorylation by extracellular signal-regulated kinase 2 at specific sites.
AB  - Analysis of phosphorylation of tau, the microtubule-associated proteins
      hyperphosphorylated in Alzheimer's disease, is often performed using
      phosphorylation-sensitive monoclonal antibodies thought to report the presence or
      absence of one or two specific phosphorylations (cognate sites). Using several
      such antibodies we found a much more complicated relationship between
      phosphorylation at specific sites, as monitored by two-dimensional phosphopeptide
      mapping, and antibody recognition of these sites. Multiple phosphorylation of tau
      in several stages by the brain extracellular signal-regulated kinase 2 isoform
      PK40 suggested that phosphorylation at cognate sites is sometimes necessary (but
      not sufficient) to induce a change of antibody reactivity and in some cases is
      not even necessary in the background of multiple phosphorylation at other sites.
      No single phosphorylation site was found to be responsible for any level of gel
      mobility shift associated with phosphorylation. Tau acquired its maximal gel
      mobility retardation and final immunochemical profile at substoichiometric
      phosphorylation of most sites. This suggests that many alternate phosphorylation
      patterns can produce the same conformational and immunochemical presentation on
      sodium dodecyl sulfate-gel electrophoresis. Although PK40(erk2) prefers some
      phosphorylation sites, most notably Ser235, followed by Ser199 or Ser202 and
      Thr205, the phosphorylation of multiple Ser/Thr-Pro sites is not highly
      sequential. Ser396 is one of the least preferred sites and seems to require prior
      phosphorylation at Ser404.

PMID- 9020177
TI  - Identification of a novel gene encoding the yeast mitochondrial dicarboxylate
      transport protein via overexpression, purification, and characterization of its
      protein product.
AB  - A gene encoding the mitochondrial dicarboxylate transport protein (DTP) has been
      identified for the first time from any organism. Our strategy involved
      overexpression of putative mitochondrial transporter genes, selected based on
      analysis of the yeast genome, followed by purification and functional
      reconstitution of the resulting protein products. The DTP gene from the yeast
      Saccharomyces cerevisiae encodes a 298-residue basic protein which, in common
      with other mitochondrial anion transporters of known sequence and function,
      displays the mitochondrial transporter signature motif, three homologous 100
      amino acid sequence domains, and six predicted membrane-spanning regions. The
      product of this gene has been abundantly expressed in Escherichia coli where it
      accumulates in inclusion bodies. Upon solubilization of the overexpressed DTP
      from isolated inclusion bodies with Sarkosyl, 28 mg of DTP was obtained per liter
      of E. coli culture at a purity of 75%. The purified, overexpressed DTP was then
      reconstituted in phospholipid vesicles where both its kinetic properties (i.e. Km
      = 1. 55 mM and Vmax = 3.0 micro;mol/min/mg protein) and its substrate specificity
      were determined. The intraliposomal substrates malonate, malate, succinate, and
      phosphate effectively supported [14C]malonate uptake, whereas other anions tested
      did not. External substrate competition studies revealed a similar specificity
      profile. Inhibitor studies indicated that the reconstituted transporter was
      sensitive to inhibition by n-butylmalonate, p-chloromercuribenzoate, mersalyl,
      and to a lesser extent pyridoxal 5'-phosphate but was insensitive to N
      ethylmaleimide and selective inhibitors of other mitochondrial anion
      transporters. In combination, the above findings indicate that the identified
      gene encodes a mitochondrial transport protein which upon overexpression and
      reconstitution displays functional properties that are virtually identical to
      those of the native mitochondrial dicarboxylate transport system. In conclusion,
      the present investigation has resulted in identification of a gene encoding the
      mitochondrial DTP and thus eliminates a major impediment to molecular studies
      with this metabolically important transporter. Based on both structural and
      functional considerations, the yeast DTP is assignable to the mitochondrial
      carrier family. Additionally, the development of a procedure that enables the
      expression and isolation of large quantities of functional DTP provides the
      foundation for comprehensive investigations into the structure/function
      relationships within this transporter via site-directed mutagenesis, as well as
      for the initiation of crystallization trials.

PMID- 9020178
TI  - Substitution mutations in the myosin essential light chain lead to reduced actin
      activated ATPase activity despite stoichiometric binding to the heavy chain.
AB  - Myosin essential light chain (ELC) wraps around an alpha-helix that extends from
      the myosin head, where it is believed to play a structural support role. To
      identify other role(s) of the ELC in myosin function, we have used an alanine
      scanning mutagenesis approach to convert charged residues in loops I, II, III,
      and helix G of the Dictyostelium ELC into uncharged alanines. Dictyostelium was
      used as a host system to study the phenotypic and biochemical consequences
      associated with the mutations. The ELC carrying loop mutations bound with normal
      stoichiometry to the myosin heavy chain when expressed in ELC-minus cells. When
      expressed in wild type cells these mutants competed efficiently with the
      endogenous ELC for binding, suggesting that the affinity of their interaction
      with the heavy chain is comparable to that of wild type. However, despite
      apparently normal association of ELC the cells still exhibited a reduced
      efficiency to undergo cytokinesis in suspension. Myosin purified from these cells
      exhibited 4-5-fold reduction in actin-activated ATPase activity and a decrease in
      motor function as assessed by an in vitro motility assay. These results suggest
      that the ELC contributes to myosin's enzymatic activity in addition to providing
      structural support for the alpha-helical neck region of myosin heavy chain.

PMID- 9020179
TI  - High molecular weight protein phosphatase type 1 dephosphorylates the
      retinoblastoma protein.
AB  - pRb controls cell proliferation by restricting inappropriate entry of cells into
      the cell division cycle. As dephosphorylation of pRb during mitotic exit
      activates its growth suppressive function, identification of the protein
      phosphatase that dephosphorylates pRb, and characterization of the mechanism of
      its regulation, are essential to elucidating the mechanisms of cell growth
      control. By fractionating mitotic CV-1P cell extracts, we identify the protein
      phosphatase which dephosphorylates pRb as a type 1 serine/threonine
      phosphoprotein phosphatase (PP1). Molecular sizing analyses indicate that the
      catalytic enzyme (PP1c) is present in a high molecular weight complex, with a
      predicted molecular mass of 166 kDa. PP1-interacting proteins in the mitotic cell
      extracts are identified. Two PP1-interacting proteins (41 and 110 kDa) are shown
      to form distinct complexes with PP1c from fractions of separated mitotic cell
      extracts containing phosphorylase phosphatase activity. However, only the 110-kDa
      PP1-interacting protein is present in fractions containing pRb-directed
      phosphatase activity, identifying this protein as a putative activator of PP1
      function toward pRb during mitosis.

PMID- 9020180
TI  - Regulation of complexed and free catenin pools by distinct mechanisms.
      Differential effects of Wnt-1 and v-Src.
AB  - Cadherins are transmembrane receptors with an extracellular domain that
      participates in homophilic cell to cell adhesion and a cytoplasmic domain that
      associates with proteins called catenins. Cadherin-mediated adhesion as well as
      adhesion-independent functions for catenins play important roles in
      differentiation, development, and malignant transformation. Mechanisms that
      regulate steady-state catenin levels and cadherin-catenin complex stability are
      poorly understood, but activities of both the Wnt-1 proto-oncogene and tyrosine
      kinases are implicated. Here I define, at the biochemical level, distinct
      mechanisms that modulate steady-state catenin levels. Increased cadherin
      expression, providing more catenin binding sites, leads to selective
      stabilization of the cadherin-associated population of alpha- and beta-catenin,
      but not p120(cas). In contrast, expression of Wnt-1 leads primarily to increased
      stability of the uncomplexed pool of beta-catenin without effect on p120(cas).
      Significantly, the Wnt-1-induced stabilization of uncomplexed beta-catenin is
      independent of cadherin expression. Transformation by v-Src does not disrupt the
      catenin-cadherin complex despite the phosphorylation of E-cadherin and beta
      catenin on tyrosine. In contrast to the effects of Wnt-1, v-Src does not modulate
      the uncomplexed population of beta-catenin. p120(cas) is phosphorylated on
      tyrosine by v-Src, and this is accompanied by a significant decrease in the level
      of uncomplexed p120(cas) as well as a change in behavior of p120(cas) upon
      biochemical fractionation. Taken together these data suggest that p120(cas) and
      beta-catenin are regulated independently.

PMID- 9020181
TI  - Ras-dependent activation of c-Jun N-terminal kinase/stress-activated protein
      kinase in response to interleukin-3 stimulation in hematopoietic BaF3 cells.
AB  - Activation of the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase
      pathway in response to stimulation of the interleukin (IL)-3 or granulocyte
      macrophage colony-stimulating factor (GM-CSF) receptor was examined in mouse
      hematopoietic BaF3-derived cell lines (BaF3-N6 and -V2 cells). Significant
      increase in the activity of JNK1 was observed within 30 min following IL-3 or GM
      CSF stimulation at physiological concentrations. Dominant-negative Ras(S17N),
      which is conditionally expressed in the presence of isopropyl-1-thio-beta-D
      galactoside in BaF3-N6 cells, prevented the IL-3 stimulation of JNK1, whereas
      anisomycin-induced JNK1 activation was unaffected. Furthermore, a deletion mutant
      of the common beta subunit for IL-3 and GM-CSF receptors that consists of only
      the membrane-proximal region, including box 1 and box 2 motifs, was incapable of
      facilitating JNK1 activity as well as Ras activation. These results provide
      evidence that Ras is required for IL-3-stimulated JNK1 activation. We also
      examined if constitutively active Ras(G12V) alone could stimulate JNK1 activity
      by using the inducible expression system. Isopropyl-1-thio-beta-D-galactoside
      induction of Ras(G12V) in the BaF3-V2 cell line caused no significant increase in
      JNK1 activity, which could be activated by IL-3 or anisomycin. On the contrary,
      the extracellular signal-regulated kinase/mitogen-activated protein kinase
      pathway was fully activated following Ras(G12V) induction. Together with these
      results, it seems likely that the Ras protein is indispensable for the IL-3
      stimulation of JNK1 although Ras activation by itself is insufficient for JNK1
      activation.

PMID- 9020182
TI  - Identification of a sialidase encoded in the human major histocompatibility
      complex.
AB  - Mammalian sialidases are important in modulating the sialic acid content of cell
      surface and intracellular glycoproteins. However, the full extent of this enzyme
      family and the physical and biochemical properties of its individual members are
      unclear. We have identified a novel gene, G9, in the human major
      histocompatibility complex (MHC), that encodes a 415-amino acid protein sharing
      21-28% sequence identity with the bacterial sialidases and containing three
      copies of the Asp-block motif characteristic of these enzymes. The level of
      sequence identity between human G9 and a cytosolic sialidase identified in rat
      and hamster (28-29%) is much less than would be expected for analogous proteins
      in these species, suggesting that G9 is distinct from the cytosolic enzyme.
      Expression of G9 in insect cells has confirmed that it encodes a sialidase, which
      shows optimal activity at pH 4.6, but appears to have limited substrate
      specificity. The G9 protein carries an N-terminal signal sequence and
      immunofluorescence staining of COS7 cells expressing recombinant G9 shows
      localization of this sialidase exclusively to the endoplasmic reticulum. The
      location of the G9 gene, within the human MHC, corresponds to that of the murine
      Neu-1 locus, suggesting that these are analogous genes. One of the functions
      attributed to Neu-1 is the up-regulation of sialidase activity during T cell
      activation.

PMID- 9020183
TI  - The neural cell adhesion molecule expresses a tyrosine-independent basolateral
      sorting signal.
AB  - Transmembrane isoforms of the neural cell adhesion molecule, N-CAM (N-CAM-140 and
      N-CAM-180), are vectorially targeted from the trans-Golgi network to the
      basolateral domain upon expression in transfected Madin-Darby canine kidney cells
      (Powell, S. K., Cunningham, B. A., Edelman, G. M., and Rodriguez-Boulan, E.
      (1991) Nature 353, 76-77). To localize basolateral targeting information, mutant
      forms of N-CAM-140 were constructed and their surface distribution analyzed in
      Madin-Darby canine kidney cells. N-CAM-140 deleted of its cytoplasmic domain
      shows a non-polar steady state distribution, resulting from delivery from the
      trans-Golgi network to both the apical and basolateral surfaces. This result
      suggests that entrance into the basolateral pathway may occur without cytoplasmic
      signals, implying that apical targeting from the trans-Golgi network is not a
      default mechanism but, rather, requires positive sorting information. Subsequent
      construction and analysis of a nested set of C-terminal deletion mutants
      identified a region of 40 amino acids (amino acids 749-788) lacking tyrosine
      residues required for basolateral targeting. Addition of these 40 amino acids is
      sufficient to restore basolateral targeting to both the non-polar cytoplasmic
      deletion mutant of N-CAM as well as to the apically expressed cytoplasmic
      deletion mutant of the p75 low affinity neurotrophin receptor (p75(NTR)),
      indicating that this tyrosine-free sequence is capable of functioning
      independently as a basolateral sorting signal. Deletion of both cytoplasmic and
      transmembrane domains resulted in apical secretion of N-CAM, demonstrating that
      the ectodomain of this molecule carries recessive apical sorting information.

PMID- 9020184
TI  - Mitogen-activated protein kinase phosphatases inactivate stress-activated protein
      kinase pathways in vivo.
AB  - The c-Jun N-terminal protein kinases (JNKs), also called stress-activated protein
      kinases, are members of the growing family of serine/threonine kinases in the
      mitogen-activated protein (MAP) kinase superfamily. Like other MAP kinases, JNKs
      are activated via phosphorylation on adjacent threonine and tyrosine residues and
      can be inactivated by a unique family of dual specificity phosphatases, called
      MAP kinase phosphatases (MKPs). MKPs are encoded by immediate early genes and
      induced in response to environmental stressors and growth factor stimulation. Two
      prevalent isoforms of MKP, MKP1 and MKP2, are co-expressed in a wide variety of
      cell types. In this study, we examined the actions of MKP1 and MKP2 on JNK1 and
      JNK2. JNK1 phosphorylation and activation was inhibited by expression of both
      MKP1 and MKP2, although MKP1 selectivity toward JNK1 appeared significantly
      higher than that of MKP2. In contrast, JNK2 activity was inhibited by either
      phosphatase to similar degrees. Both MKP1 and MKP2 were highly effective at
      blocking the activation of the physiological target of JNK activation, the
      transcription factor c-Jun. In PC12 cells, MKP1 and MKP2 are transcriptionally
      induced following stimulation by nerve growth factor. In these cells, UV light
      evoked JNK activation was reduced by pretreatment with nerve growth factor.
      Therefore, JNKs may be selective targets of MKP action in certain cells.

PMID- 9020185
TI  - Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL)
      requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL.
AB  - TAL1, which is frequently activated in T cell acute lymphoblastic leukemia (T
      ALL), encodes lineage-specific basic helix-loop-helix (bHLH) proteins that bind
      specifically to E-box DNA motif upon dimerization with ubiquitous basic helix
      loop-helix proteins E47 or E12. RBTN1 and RBTN2, also frequently activated in T
      ALL, encode proteins only with tandem cysteine-rich LIM domains. We found that
      aberrant expression of TAL1 detected in 11 out of 14 T-ALL cell lines was
      invariably accompanied by that of either RBTN1 or RBTN2. Forced expression of
      TAL1 together with RBTN1 or RBTN2, but not TAL1 alone, strongly induced
      artificial reporter genes in a TAL1/RBTN-negative T-ALL cell line, HPB-ALL. Such
      collaborative transcriptional activity of TAL1 and RBTN was not, however,
      observed in non-T cell lines, suggesting further involvement of some T cell
      specific cofactors. In this context, we carried out preliminary evaluation of a
      potential role of the T cell-specific GATA-binding protein, GATA3, in the
      transcriptional activity of TAL1 and RBTN. We also showed that coexpression of
      TAL1 and RBTN1 in HPB-ALL strongly induced TALLA1, a highly specific T-ALL marker
      whose positivity correlated 100% with ectopic expression of TAL1 among various T
      ALL cell lines. Collectively, ectopic TAL1 and RBTN1 or -2, together with some
      endogenous T cell-specific cofactors like GATA3, constitute a highly
      collaborative set of transcription factors whose aberrant activity in T cells may
      lead to leukemogenesis by modulating expression of downstream genes such as
      TALLA1.

PMID- 9020186
TI  - A structural change occurs upon binding of syntaxin to SNAP-25.
AB  - The highly conserved proteins syntaxin and SNAP-25 are part of a protein complex
      that is thought to play a key role in exocytosis of synaptic vesicles. Previous
      work demonstrated that syntaxin and SNAP-25 bind to each other with high affinity
      and that their binding regions are predicted to form coiled coils. Circular
      dichroism spectroscopy was used here to study the alpha-helicity of the
      individual proteins and to gain insight into structural changes associated with
      complex formation. Syntaxin displayed approximately 43% alpha-helical content. In
      contrast, the alpha-helical content of SNAP-25 was low under physiological
      conditions. Formation of the SNAP-25-syntaxin complex was associated with a
      dramatic increase in alpha-helicity. Interaction of a 90-residue NH2-terminal
      fragment of SNAP-25 comprising the minimal syntaxin binding domain lead to a
      similar but less pronounced increase in alpha-helicity. Single amino acid
      replacements in the putative hydrophobic core of this fragment with hydrophilic
      amino acids abolished the induced structural change and disrupted the interaction
      monitored by binding assays. Replacements with hydrophobic residues had no
      effect. Our findings are consistent with induced coiled coil formation upon
      binding of syntaxin and SNAP-25.

PMID- 9020187
TI  - Protein-disulfide isomerase-mediated reduction of the A subunit of cholera toxin
      in a human intestinal cell line.
AB  - A key step in the action of cholera toxin (CT) is the reduction of its A subunit
      to the A1 peptide. The latter is an ADP-ribosyltransferase, which activates the
      alpha-subunit of the stimulatory G protein of adenylyl cyclase. In this study,
      the enzymatic reduction of membrane-bound CT in CaCo-2 human intestinal
      epithelial cells was characterized. Whereas diphtheria toxin was found to be
      reduced by a cell surface population of protein-disulfide isomerase (PDI) and its
      cytotoxicity was inhibited by p-chloromercuribenzenesulfonic acid, bacitracin, or
      anti-PDI antibodies, these inhibitors had no effect on CT reduction or activity
      in intact cells. In contrast, the reduction of CT in vitro by either postnuclear
      supernatants (PNS) or microsomal membranes in the presence of Triton X-100 was
      significantly inhibited by p-chloromercuribenzenesulfonic acid and bacitracin.
      Anti-PDI monoclonal antibodies likewise inhibited the in vitro reduction of CT
      and also were effective in depleting reductase activity from PNS. Since
      inhibition and depletion were not observed in the absence of detergent, these
      results suggested that the reductase activity was a soluble component localized
      to the lumen of microsomal vesicles and correlated with the presence of protein
      disulfide isomerase. This was further confirmed by showing a corresponding
      depletion of reductase activity and PDI in alkali-treated microsomes. This
      activity was restored when purified bovine PDI was added back to alkali-treated
      microsomes in a redox buffer that reflected conditions found in the lumen of the
      endoplasmic reticulum (ER). When the CT-related reductase activity was assayed in
      subcellular fractions of PNS-derived membranes isolated on a 9-30% Iodixanol
      gradient, the activity, as measured by CT-A1 peptide formation localized to those
      fractions containing PDI. Likewise CT-A1 peptide formed in intact cells co
      localized to those membrane fractions containing the majority of cellular PDI.
      Furthermore, the banding density corresponded to a region of the gradient
      containing ER-derived membranes. These results indicated that CT was a substrate
      for PDI-catalyzed reduction in intact cells and supported the hypothesis that CT
      reduction and activation occurs in the ER.

PMID- 9020188
TI  - Stat2 is a transcriptional activator that requires sequence-specific contacts
      provided by stat1 and p48 for stable interaction with DNA.
AB  - Transcriptional responses to interferon (IFN) are mediated by tyrosine
      phosphorylation and nuclear translocation of transcription factors of the signal
      transducer and activator of transcription (Stat) family. The Stat1 protein is
      required for all transcriptional responses to IFN (both type I and type II).
      Responses to type I IFN (alpha and beta) also require Stat2 and the IFN
      regulatory factor family protein p48, which form a heterotrimeric transcription
      complex with Stat1 termed ISGF3. Stat1 homodimers formed in response to IFN-gamma
      treatment can also interact with p48 and function as transcriptional activators.
      We now show that Stat2 is capable of forming a stable homodimer that interacts
      with p48, can be recruited to DNA, and can activate transcription, raising a
      question of why Stat1 is required. Analysis of the transcriptional competence,
      affinity, and specificity of Stat2-p48 complexes compared with other Stat protein
      containing transcription factor complexes suggests distinct roles for each
      component. Although Stat2 is a potent transactivator, it does not interact stably
      with DNA in complex with p48 alone. Adding Stat1 increases the affinity and
      alters the sequence selectivity of p48-DNA interactions by contacting a half-site
      of its palindromic recognition motif adjacent to a p48 interaction sequence.
      Thus, ISGF3 assembly involves p48 functioning as an adaptor protein to recruit
      Stat1 and Stat2 to an IFN-alpha-stimulated response element, Stat2 contributes a
      potent transactivation domain but is unable to directly contact DNA, while Stat1
      stabilizes the heteromeric complex by contacting DNA directly.

PMID- 9020189
TI  - Phosducin, potential role in modulation of olfactory signaling.
AB  - Phosducin, which tightly binds betagamma-subunits of heterotrimeric G-proteins,
      has been conjectured to play a role in regulating second messenger signaling
      cascades, but to date its specific function has not been elucidated. Here we
      demonstrate a potential role for phosducin in regulating olfactory signal
      transduction. In isolated olfactory cilia certain odorants elicit a rapid and
      transient cAMP response, terminated by a concerted process which requires the
      action of two protein kinases, protein kinase A (PKA) and a receptor-specific
      kinase (GRK3) (Schleicher, S., Boekhoff, I. Arriza, J., Lefkowitz, R. J., and
      Breer, H. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 1420-1424). The mechanism of
      action of GRK3 involves a Gbetagamma-mediated translocation of the kinase to the
      plasma membrane bound receptors (Pitcher, J. A., Inglese, J., Higgins, J. B. ,
      Arriza, J. L., Casey, P. J., Kim, C., Benovic, J. L., Kwatra, M. M. , Caron, M.
      G., and Lefkowitz, R. J. (1992) Science 257, 1264-1267). A protein with a
      molecular mass of 33 kDa that comigrates on SDS gels with recombinant phosducin
      and which is immunoreactive with phosducin antibodies is present in olfactory
      cilia. Recombinant phosducin added to permeabilized olfactory cilia preparations
      strongly inhibits termination of odorant-induced cAMP response and odorant
      induced membrane translocation of GRK3. In addition, the cAMP analogue dibutyryl
      cAMP stimulates membrane targeting of the receptor kinase. This effect is
      presumably due to PKA-mediated phosphorylation of phosducin, which diminishes its
      affinity for binding to the Gbetagamma-subunit, thereby making Gbetagamma
      available to function as a membrane anchor for GRK3. A specific PKA inhibitor
      blocks the odorant-induced translocation of the receptor kinase. Consistent with
      this formulation, a non-phosphorylatable mutant of phosducin (phosducin Ser-73 -
      > Ala) is an even more effective inhibitor of desensitization and membrane
      targeting of GRK3 than the wild-type protein. A phosducin mutant that mimics
      phosphorylated phosducin (phosducin Ser-73 --> Asp) lacks this property and in
      fact recruits GRK3 to the membrane and potentiates desensitization. These results
      suggest that phosducin may act as a phosphorylation-dependent switch in second
      messenger signaling cascades, regulating the kinetics of desensitization
      processes by controlling the activity of Gbetagamma-dependent GRKs.

PMID- 9020190
TI  - Genomic footprinting of Mig1p in the MAL62 promoter. Binding is dependent upon
      carbon source and competitive with the Mal63p activator.
AB  - Mig1p inhibits gene expression in glucose by binding the Cyc8p (Ssn6p)-Tup1p
      repressor to the promoter of glucose-repressible genes. While the binding
      properties of Mig1p have been studied in vitro and the ability of Mig1p-Cyc8p
      (Ssn6p)-Tup1p to repress has been studied in vivo, no experiments have measured
      the effect of a carbon source on the in vivo binding of Mig1p or the effect of
      bound MIg1p on activator occupancy of the upstream activation sequence (UAS). To
      obtain this information, we used genomic footprinting to investigate glucose
      repression of MAL62, a gene that is also regulated by the Mal63p activator. These
      experiments show that two interrelated mechanisms are involved in the glucose
      repression of MAL62: 1) competition between the Mal63p activator and Mig1p for
      DNA binding and 2) modulation of Mig1p binding by the carbon source. Mig1p
      affects basal MAL62 expression in the absence of Mal63p by binding to a site in
      the MAL62 promoter and affects Mal63p-dependent synthesis by also inhibiting the
      access of Mal63p to site 1 in the UASMAL. The binding of Mig1p is increased in
      glucose and decreased in nonrepressing sugars, but the increased binding in
      glucose is not due to an increase in the levels of Mig1p.

PMID- 9020191
TI  - Biochemical analyses of mutations in the HSV-1 helicase-primase that alter ATP
      hydrolysis, DNA unwinding, and coupling between hydrolysis and unwinding.
AB  - Herpes simplex virus type 1 encodes a heterotrimeric helicase-primase composed of
      the products of the UL5, UL52, and UL8 genes. UL5 possesses six motifs conserved
      among superfamily 1 of helicase proteins. Substitutions of conserved residues in
      each motif abolishes DNA replication in vivo (Zhu, L., and Weller, S. K. (1992)
      J. Virol. 66, 469-479). Purified UL5.52 harboring a Gly to Ala change in motif V
      retains primase and helicase activities in vitro but exhibits a higher KM for
      single-stranded DNA and lower DNA-dependent ATPase activity (Graves-Woodward, K.
      L., and Weller, S. K. (1996) J. Biol. Chem. 272, 13629-13635). We have purified
      and characterized six other subcomplexes with residue changes in the UL5 helicase
      motifs. Each variant subcomplex displays at least wild type or greater levels of
      primase and DNA binding activities, but all are defective in helicase activity.
      Mutations in motifs I and II exhibit profound decreases in DNA-dependent ATPase
      activity. Mutations in motifs III-VI decrease DNA-dependent ATPase activity 3-6
      fold. Since mutations in motifs III, IV, V, and VI do not eliminate ATP
      hydrolysis or DNA binding, we propose that they may be involved in the coupling
      of these two activities to the process of DNA unwinding. This analysis represents
      the first comprehensive structure-function analysis of the conserved motifs in
      helicase superfamily 1.

PMID- 9020192
TI  - c-Jun NH2-terminal kinase-mediated activation of interleukin-1beta converting
      enzyme/CED-3-like protease during anticancer drug-induced apoptosis.
AB  - Upon treatment with various anticancer drugs, myeloid leukemia U937 cells undergo
      apoptosis. In this study, we found that either etoposide (VP-16) or camptothecin
      (CPT) activated c-Jun N-terminal kinase 1/stress-activated protein kinase
      (JNK1/SAPK), transient c-jun expression, and ICE (interleukin-1beta converting
      enzyme)/CED-3-like proteases in U937 cells. Phorbol ester-resistant U937 variant,
      UT16 cells, displayed a decreased susceptibility to apoptosis induced by these
      drugs. The drugs did not cause JNK1 activation, c-jun expression, nor activation
      of ICE/CED-3-like proteases in UT16 cells. As reported previously,
      benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-Asp), a preferential
      inhibitor of ICE/CED-3-like proteases, blocked the apoptosis of U937 cells.
      Interestingly, however, Z-Asp did not inhibit JNK1 activation in either VP-16- or
      CPT-treated U937 cells. The JNK1 antisense oligonucleotides diminished protein
      expression of JNK1 and inhibited drug-induced apoptosis of U937 cells, whereas
      sense control oligonucleotides did not. Consistent with this observation, the
      antisense oligonucleotide-treated cells did not respond to VP-16 or CPT with Z
      Asp-sensitive proteases. These results indicate that JNK1 triggers the DNA
      damaging drug-induced apoptosis of U937 cells by activating Z-Asp-sensitive
      ICE/CED-3-like proteases.

PMID- 9020193
TI  - Gbetagamma subunits mediate Src-dependent phosphorylation of the epidermal growth
      factor receptor. A scaffold for G protein-coupled receptor-mediated Ras
      activation.
AB  - In many cells, stimulation of mitogen-activated protein kinases by both receptor
      tyrosine kinases and receptors that couple to pertussis toxin-sensitive
      heterotrimeric G proteins proceed via convergent signaling pathways. Both signals
      are sensitive to inhibitors of tyrosine protein kinases and require Ras
      activation via phosphotyrosine-dependent recruitment of Ras guanine nucleotide
      exchange factors. Receptor tyrosine kinase stimulation mediates ligand-induced
      receptor autophosphorylation, which creates the initial binding sites for SH2
      domain-containing docking proteins. However, the mechanism whereby G protein
      coupled receptors mediate the phosphotyrosine-dependent assembly of a mitogenic
      signaling complex is poorly understood. We have studied the role of Src family
      nonreceptor tyrosine kinases in G protein-coupled receptor-mediated tyrosine
      phosphorylation in a transiently transfected COS-7 cell system. Stimulation of Gi
      coupled lysophosphatidic acid and alpha2A adrenergic receptors or overexpression
      of Gbeta1gamma2 subunits leads to tyrosine phosphorylation of the Shc adapter
      protein, which then associates with tyrosine phosphoproteins of approximately 130
      and 180 kDa, as well as Grb2. The 180-kDa Shc-associated tyrosine phosphoprotein
      band contains both epidermal growth factor (EGF) receptor and p185(neu). 3-5-fold
      increases in EGF receptor but not p185(neu) tyrosine phosphorylation occur
      following Gi-coupled receptor stimulation. Inhibition of endogenous Src family
      kinase activity by cellular expression of a dominant negative kinase-inactive
      mutant of c-Src inhibits Gbeta1gamma2 subunit-mediated and Gi-coupled receptor
      mediated phosphorylation of both EGF receptor and Shc. Expression of Csk, which
      inactivates Src family kinases by phosphorylating the regulatory carboxyl
      terminal tyrosine residue, has the same effect. The Gi-coupled receptor-mediated
      increase in EGF receptor phosphorylation does not reflect increased EGF receptor
      autophosphorylation, assayed using an autophosphorylation-specific EGF receptor
      monoclonal antibody. Lysophosphatidic acid stimulates binding of EGF receptor to
      a GST fusion protein containing the c-Src SH2 domain, and this too is blocked by
      Csk expression. These data suggest that Gbetagamma subunit-mediated activation of
      Src family nonreceptor tyrosine kinases can account for the Gi-coupled receptor
      mediated tyrosine phosphorylation events that direct recruitment of the Shc and
      Grb2 adapter proteins to the membrane.

PMID- 9020194
TI  - Structural basis for the haemotoxicity of dapsone: the importance of the
      sulphonyl group.
AB  - The structural basis of dapsone (4,4'-diaminodiphenyl sulphone) haemotoxicity has
      been determined by investigation of the in vitro bioactivation of a series of 4
      substituted arylamines. In the presence of rat liver microsomes, dapsone (100
      microM) was the most potent former of methaemoglobin in human erythrocytes (44.8
      +/- 6.7%). Substitution of the sulphone group with sulphur (11.6 +/- 1.4%
      methaemoglobin), oxygen (4.5 +/- 1.1%), nitrogen (0.0 +/- 3.2%), carbon (13.6 +/-
      0.8%) or a keto group (34.0 +/- 6.1%) resulted in a decrease in methaemoglobin
      formation. Only one compound, 4,4'-diaminodiphenylamine, generated significant (P
      < 0.001) amounts of methaemoglobin (25.6 +/- 2.5%) in the absence of NADPH. To
      assess further the role of the 4-substituent in methaemoglobinaemia, the toxicity
      of a series of 4-substituted aniline derivatives was also studied. Of the
      anilines studied, 4-nitroaniline caused the most methaemoglobin (36.5 +/- 8.0%),
      whilst aniline caused the least (0.3 +/- 0.5%). Overall, there was a significant
      correlation (r2 = 0.83) between the haemotoxicity and the Hammett constant,
      sigma(p), suggesting that it is the electron-withdrawing properties of the
      substituent that influence the methaemoglobin formation. In the presence of
      microsomes prepared from two human livers, dapsone was the most haemotoxic bis
      arylamine, whereas 4-iodoaniline was the most potent methaemoglobin former (60.6
      and 73.6%) and aniline the least potent (1.1 and 2.4%). As a whole, these results
      indicate that the sulphonyl group, which is essential for the pharmacological
      activity of dapsone, is also largely responsible for the haemotoxicity seen with
      this drug.

PMID- 9020195
TI  - Interaction of methadone with substrates of human hepatic cytochrome P450 3A4.
AB  - Methadone, a synthetic drug, is one of the most widely used drugs for opiate
      dependency treatment. This drug has been demonstrated to be extensively
      metabolized by cytochrome P450 3A4 in human liver microsomes. Thus, the aim of
      this in vitro study was to determine if methadone is an inhibitor of other P450s
      characterized by their specific catalytic activities. Enzymatic activities
      specific to P450 2E1, P450 1A, P450 2B and P450 2C were not inhibited by
      methadone. Conversely, nifedipine oxidation, mediated by cytochrome P450 3A4, was
      potently inhibited by methadone by a mixed-type inhibition mechanism with a Ki of
      100 microM. Fluvoxamine, a new antidepressant, was shown to be a potent mixed
      type inhibitor of methadone N-demethylation with a Ki of 7 microM. Finally,
      methadone appears to be a mixed-type inhibitor and not a suicide inhibitor of
      cytochrome P450 3A family. Accordingly, caution should be advised in the clinical
      use of methadone when other drugs are administered that are able to induce or
      inhibit P450 3A4, such as rifampicin or nifedipine, diazepam and fluvoxamine.

PMID- 9020196
TI  - A pharmacokinetic model describing pulsatile uptake of orally-administered carbon
      tetrachloride.
AB  - Many rodent bioassays have been conducted using oral gavage for delivery of test
      chemicals. Highly lipophilic compounds are generally administered to rodents
      dissolved in corn oil, a dosing vehicle shown to influence xenobiotic toxicity,
      carcinogenicity and pharmacokinetics by altering chemical absorption processes.
      In this paper, we present a multi-compartmental description of the
      gastrointestinal (GI) tract linked to a physiologically based pharmacokinetic (PB
      PK) model to describe the complex oral uptake of carbon tetrachloride (CCl4)
      administered in corn oil and 0.25% Emulphor. The GI submodel was described using
      a series of subcompartments, each subcompartment described with an absorption
      constant (Ka, 1/h), a bioavailability term (A, unitless), and a compartment
      emptying time (T, h). The model was parameterized by fitting multi-peak blood and
      exhaled breath chamber concentration-time profiles following oral gavage of CCl4
      in corn oil and aqueous vehicles to male Fischer 344 rats. Successful fitting of
      experimental data was accomplished by varying values of Ka, A, and T until
      adequate fits were obtained. Values of Ka and A required to fit data from aqueous
      gavage were greater than corn oil. Utilization of the multi-compartmental GI
      tract submodel provided increased precision in fitting complex oral uptake
      profiles compared to previously used one- and two-compartment oral uptake models.
      This model provides estimates of absorption rate constants and bioavailabilities
      as well as providing a framework for generation of more complete, physiologically
      realistic descriptions of oral absorption.

PMID- 9020197
TI  - Membrane toxicity of opioids measured by protozoan motility.
AB  - The acute toxicity of some opioid drugs cannot solely be explained by a specific
      interaction with the opioid receptor. The anaesthetic-like membrane effect of 10
      opioid agents and the antagonist naloxone was determined and correlated with
      their hydrophobicity. The inhibitory effect of drugs on protozoan motility was
      used as a measure of their membrane toxicity, measured by the reduction in
      swimming speed of Tetrahymena pyriformis using an image analysis system.
      Hydrophobicity was determined as the n-octanol/water partition coefficient, at pH
      7.4, 37 degrees C. Opioid agents dose-dependently reduced the swimming speed of
      Tetrahymena pyriformis with a wide range of IC50 values. Some weak opioid agents
      were shown to have high protozoan immobilising potency comparable to quinidine,
      an agent with known membrane stabilising activity. Norpropoxyphene, the
      metabolite of dextropropoxyphene, with little affinity for the opioid receptor,
      also had a high potency. The inhibition of protozoan motility by these opioid
      agents was not antagonised by the opioid receptor antagonist naloxone; moreover
      an additive inhibitory action was demonstrated when opioid agents were combined
      with naloxone. The effect of opioid agents on protozoan motility was closely
      correlated with their partition coefficient but not with their known affinity for
      opioid receptors. These results suggest that opioid agents possess differing
      degrees of membrane depressant action independent from their interaction with the
      opioid receptor, and have a potential for causing depressant effects on excitable
      tissues.

PMID- 9020198
TI  - Biphasic effects of chromium compounds on catecholamine secretion from bovine
      adrenal medullary cells.
AB  - CrO3 was found to affect norepinephrine release in a biphasic manner: at
      concentrations above 100 microM, it inhibited, while at concentrations below 10
      microM, it enhanced DMPP- and high K+-induced [3H]norepinephrine (NE) release
      from bovine adrenal medullary cells. Similar effects were found for K2Cr2O7. CrO3
      inhibited the 45Ca2+ uptake induced by DMPP and high K+, suggesting that the
      voltage-gated Ca2+ channels are possible sites of the inhibitory action of CrO3.
      CrCl3, possessing a trivalent state in contrast to the hexavalent states of CrO3,
      K2Cr2O7, inhibited DMPP-induced [3H] release and inhibited, to a lesser extent,
      high K+-induced [3H]-NE release, suggesting that nicotinic receptors are also
      possible sites of Cr3+ action. In medullary cells permeabilized with digitonin,
      both CrO3 and CrCl3 induced [3H]-NE release from cells preloaded with [3H]-NE. In
      intact cells, CrO3 but not CrCl3 enhanced secretagogue-induced [3H]-NE release
      and entered into the cells as demonstrated by fluorescence quenching experiments.
      These results suggest that chromium compounds can induce catecholamine secretion
      after entering the cytoplasm. The enhancement of norepinephrine release induced
      by chromium ions appears to be due to interference with the intracellular
      functions of Ca2+ in the cytoplasm.

PMID- 9020199
TI  - Oxidative liver DNA damage in rats treated with pesticide mixtures.
AB  - Oxidative damage was quantified in the liver of rats by measuring the levels of 8
      OH-2-deoxyguanosine (8-OH-2DG) relative to 2-deoxyguanosine in DNA after treating
      rats for 10 days at a total dose of 1 mg/kg/day with a mixture of the 15
      pesticides most commonly found in Italian foods (comprised of dithiocarbamate,
      benomyl, procymidone, methidathion, chlorpyrifos-ethyl, parathion-methyl,
      chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos ethyl,
      thiabendazole, fenarimol, diphenylamine and chlorothalonil). We fractionated this
      pesticide mixture into subgroups in order to determine which molecules, if any,
      induced DNA oxidative damage. The administration of diphenylamine (0.09-1.4
      mg/kg/day) and chlorothalonil (0.13-1 mg/kg/day) induced a dose-dependent
      increase in 8-OH-2DG levels in liver DNA. The other 13 pesticides of the mixture
      on the contrary, did not produce oxidative liver DNA damage. These results
      indicate that the toxicity of low doses of pesticide mixtures present in food
      might be further reduced by eliminating diphenylamine and chlorothalonil.

PMID- 9020200
TI  - Effects of triethyl lead administration on the expression of glutathione S
      transferase isoenzymes and quinone reductase in rat kidney and liver.
AB  - The effects of triethyl lead chloride (TEL) on the expression of two detoxication
      enzyme families, glutathione S-transferases (GSTs) and NAD(P)H:quinone
      oxidoreductase (QR) were determined in rat liver and kidney. Fischer 344 rats
      were given one intraperitoneal (i.p.) injection of TEL. GST activity, GST
      isoenzyme levels, mRNA levels of alpha class GST isoenzymes Ya1, Ya2, and Yc1 and
      activity of QR were determined. Treatment of rats with TEL caused a significant
      increase in GST activity in kidney. In kidney, the levels of all GST subunits
      were significantly elevated; the largest increase was a 3.2-fold increase in GST
      Yb1. The levels of GST Ya1, Ya2, and Yc1 mRNA also increased after injection of
      TEL. In liver, TEL injection resulted in decreased GST activity and lower levels
      of hepatic GSTs Yb2, Yb3, Ya1, and Ya2. The largest decrease was a 40% reduction
      of GST Ya1. In contrast, the level of liver GST Yc1 increased from day 4 through
      day 14 after injection of 10 mg/kg TEL and Yp was increased 1.4-fold 4 days after
      injection of 12 mg/kg TEL. The levels of liver mRNAs coding for alpha class GSTs
      Ya1, Ya2, and Yc1 were reduced 12 h after injection of TEL. The mRNA levels of
      GST Ya1 and Ya2 returned to basal level while Yc1 message increased to a level
      higher than controls 24 h after TEL injection. The increase in Yc1 protein
      between days 4 and 14 is consistent with the increase in the corresponding mRNA.
      The activity of QR was elevated 1.5-fold in kidney and 2.7-fold in liver 14 days
      after the injection of TEL. This report demonstrates that administration of
      organic lead significantly affects GST expression and QR activity in a tissue
      specific and isoenzyme-specific manner. These results indicate that GST
      expression and QR activity are not co-regulated.

PMID- 9020201
TI  - The effect of aromatic fluorine substitution on the nephrotoxicity and metabolism
      of N-(3,5-dichlorophenyl)succinimide in Fischer 344 rats.
AB  - N-(3,5-Difluorophenyl)succinimide (DFPS) is a non-toxic analogue of the
      nephrotoxic fungicide N-(3,5-dichlorophenyl)succinimide (NDPS). Although NDPS
      must be metabolized to produce renal damage, the metabolic fate of DFPS is
      unknown. These studies were therefore designed to examine the nephrotoxic
      potential of putative DFPS metabolites and to determine if DFPS is metabolized
      differently from NDPS. Male Fischer-344 rats were administered (1.0 mmol/kg. i.p.
      in corn oil) DFPS, N-(3,5-difluorophenyl)succinamic acid (DFPSA), N-(3,5
      difluorophenyl)-2-hydroxysuccinimide (DFHS), N-(3,5-difluorophenyl)-2- or -3
      hydroxysuccinamic acids (2- and 3-DFHSA, respectively), N-(3,5-difluoro-4
      hydroxyphenyl)succinimide (DFHPS). N-(3,5-difluoro-4-hydroxyphenyl) succinamic
      acid (DFHPSA) or corn oil only (1.2 ml/kg). Although some of the compounds
      produced changes in renal function and histology, these alterations were not
      indicative of irreversible kidney damage. DFPSA, 2-DFHSA, 3-DFHSA and DFHPSA were
      detected in the urine of rats 3 h after administration of 0.2 mmol/kg [14C]DFPS.
      The same metabolites were produced by isolated rat hepatocytes, but not by renal
      proximal tubule cells. Formation of the oxidative metabolites in vitro was
      prevented by the cytochrome P450 inhibitor 1-aminobenzotriazole. It appears that
      DFPS undergoes hepatic biotransformation similar to NDPS and that some of its
      metabolites have reversible effects on renal proximal tubules.

PMID- 9020202
TI  - Method of spinal fusion.

PMID- 9020203
TI  - Basic science of spinal instrumentation.
AB  - A wide variety of spinal implants are available to the clinician for the surgical
      treatment of spinal disorders. Most of the implants are associated with fusion-
      they are designed either to promote fusion, or, in the case of the newer devices
      such as artificial discs and disc implants, to offset the perceived disadvantages
      of fusion. The contributions of biomechanics to the improvement of spinal implant
      design and clinical implementation are detailed. Benchtop tests of device
      components and assemblies, in vitro studies of spinal constructs using
      osteoligamentous spinal segments, and analytical (finite element) and animal
      models are reviewed. Through these studies, the quantification of parameters such
      as stresses and strains within the spinal structures and within the fixation
      devices has permitted a better understanding of the relationship between the
      clinical observations after surgery and the mechanical factors. However, despite
      improvements in fusion techniques that have reduced the pseudarthrosis rate,
      there is still room for improvement. New concepts such as the biological
      enhancement of spinal fusion and alternatives to fusion such as the artificial
      disc are currently the subjects of intense, multidisciplinary study, but await
      the ultimate test of clinical trial with long term followup.

PMID- 9020205
TI  - Spinal instrumentation in the management of degenerative disorders of the lumbar
      spine.
AB  - The use of spinal instrumentation as an adjunct to fusion for the treatment of
      degenerative disorders of the lumbar spine is controversial. Instrumented lumbar
      fusions, in specific instances, may improve patient outcomes. For patients
      undergoing single level primary lumbar arthrodesis, the available data do not
      conclusively support the efficacy of spinal instrumentation. However, in the
      setting of previous failed lumbar surgery, iatrogenic or degenerative lumbar
      spondylolisthesis, spinal instrumentation may be useful as an adjunct to fusion.
      Possible advantages associated with the use of instrumentation include:
      correction of deformity in frontal and sagittal planes; decreased pseudarthrosis
      rates; prevention of progression of spondylolisthesis, and provision of spinal
      stability in the absence of intact posterior elements. Complications associated
      with the use of instrumentation include: increased cost; increased operative
      times; increased infection rate; increased reoperation rate; and a steep learning
      curve. Therefore, when instrumentation is to be used, the benefits must outweigh
      the risks. These risks can be minimized by the judicious use of instrumentation
      by experienced surgeons, for specific indications as supported by the literature.

PMID- 9020204
TI  - Food and Drug Administration regulation of spinal implant fixation devices.
AB  - The role of the Food and Drug Administration in regulating medical devices
      generally is not well understood by physicians. The practice of medicine does not
      fall under Food and Drug Administrations's regulatory purview. Nevertheless, the
      Food and Drug Administration and its regulation of medical devices can influence
      physicians' activities. This article provides an overview of the scope of the
      Food and Drug Administration's authority and the agency's regulatory framework,
      with particular focus on orthopaedic medical devices as related to spinal implant
      devices. During the past 10 years, a regulatory dilemma has arisen surrounding
      the use of bone screws in the pedicles of the spine. Except for recent clearances
      for a limited treatment indication, the Food and Drug Administration has not
      cleared these devices to be labeled for pedicle screw fixation and, therefore,
      has restricted industry supported educational activities pertaining to this type
      of treatment. In spite of the Food and Drug Administration's regulatory position,
      physicians have chosen to use pedicle screw fixation in treating patients who
      have a variety of spinal disorders. This use is now considered an accepted (state
      of the art) medical practice by many physicians for certain spinal conditions.
      This article explores this specific Food and Drug Administration regulatory
      issue, its impact on physicians and manufacturers (especially as it pertains to
      medical education), and recent actions taken to resolve it.

PMID- 9020206
TI  - Surgical treatment of spinal tumors.
AB  - The surgical treatment of spinal tumors depends on a host of factors that
      include: the type of tumor and its location within the spine, the presence or
      absence of neural compression, the portion of the vertebrae involved, the
      anticipated mode of spinal failure, the biology of the tumor, the anticipated
      life expectancy of the patient, and the type of prior or subsequent adjuvant
      treatment. Two thirds of all spinal tumors arise from the vertebral body and only
      1/3 originate from the posterior elements. Malignant tumors more commonly involve
      the vertebral body and benign lesions usually are located posteriorly. Malignant
      tumors, because of their aggressive nature and their propensity for anterior
      vertebral body involvement, are associated with a higher incidence of neurologic
      deficit than are benign lesions. The surgical treatment of spinal tumors is
      dictated largely by the location of the tumor within the spine; anterior
      vertebral body tumors generally should be approached anteriorly, whereas
      posterior lesions should be approached posteriorly. Because most malignant
      tumors, whether primary or secondary (metastatic), are located anteriorly within
      the vertebral body, most surgery for malignant tumors should be approached
      anteriorly. Anterior decompression should be accompanied by reconstruction with
      biologic materials such as autogenous bone graft unless life expectancy is
      certain to be very limited (<6 months).

PMID- 9020207
TI  - Spinal instrumentation in the management of adolescent scoliosis.
AB  - A multitude of posterior and anterior segmental spinal instrumentation systems
      are now available for the treatment of idiopathic scoliosis. As a consequence,
      fixation strategies are more complex than they were with Harrington
      instrumentation. The newer systems provide better sagittal control and more
      stable fixation, allowing quicker mobilization of the patient. On thin patients,
      the bulk of these implants may be a problem. The techniques of fusion and the
      fusion levels remain constant.

PMID- 9020208
TI  - Posterior instrumentation for thoracolumbar trauma.
AB  - The majority of thoracolumbar spine fractures and fracture dislocations may be
      considered acute sagittal plane deformities. Unstable thoracolumbar spine
      injuries require stabilization to (1) allow mobilization of the patient to
      prevent pulmonary and venous complications; (2) to relieve pain; (3) to realign
      the spine and spinal canal, and (4) to decompress directly or indirectly the
      neural elements. Posterior spinal instrumentation is a safe, available, familiar,
      and effective method to achieve these goals. Posterior spinal instrumentation
      techniques used rod hook systems or screw rod and screw plate systems. Most of
      these unstable injuries can be managed using these well established techniques
      without the need for additional combined or staged anterior spinal surgery.

PMID- 9020209
TI  - Anterior instrumentation in the management of thoracolumbar burst fractures.
AB  - Anterior instrumentation in the treatment of thoracolumbar fractures has
      progressed significantly during the past 2 decades. These fixation systems have
      evolved to meet the anatomic, biomechanical, and imaging challenges associated
      with internal fixation of the thoracolumbar spine. The evolution of these devices
      will be reviewed, and from this, the indications and surgical techniques
      necessary for the safe and effective use of the device will be discussed. This
      study also reports the authors' initial clinical experience using the Z plate
      anterior thoracolumbar plating system in the treatment of thoracolumbar burst
      fractures. The study consists of 12 consecutive adult patients who underwent a 1
      stage anterolateral decompressive and stabilization procedure for burst fractures
      from T9-L3. The indications for surgery included neurologic deficits, deformity,
      progressive kyphosis, and late pain. Ten of the 12 patients maintained their
      postoperative sagittal alignment or a significant portion of their kyphosis
      reduction. Two patients with severe kyphotic deformities greater than 50 degrees
      lost 10 degrees and 20 degrees of their reduction at last followup. All 3
      patients with neurologic deficits recovered. There were no neurologic or
      perioperative complications. Eleven of the 12 patients obtained a good or
      excellent functional outcome. Anterior arthrodesis using instrumentation
      stabilization after a 1-stage anterolateral decompression and reduction procedure
      can yield successful clinical results in the treatment of thoracolumbar burst
      fractures.

PMID- 9020210
TI  - Posterior cervical fixation for fracture and degenerative disc disease.
AB  - There are numerous newer techniques that have been developed for the internal
      fixation of the cervical spine in recent years. Wiring techniques are still
      appropriate for posterior stabilization of the cervical spine. The halo vest is
      still widely used for the conservative management of cervical fractures and for
      postoperative external immobilization. The authors stress that the surgical
      indications for more modern rigid implants should be adhered to strictly. These
      implants also should be selected by weighing their advantages versus potential
      risks. In the upper cervical spine, the surgeon may choose traditional wiring
      methods and newer C1-C2 screw fixation, occipitocervical plate fixation. For the
      lower cervical spine, triple wiring technique or lateral mass plating may be
      used. The surgeon must choose an appropriate device based on the mechanism of
      injury, pathoanatomy of the lesion, and familiarity with the device, keeping in
      mind that the goals of internal fixation are stabilization, reduction and
      maintenance of alignment, early rehabilitation and perhaps enhancement of fusion
      rates, and avoidance of use of an external halo vest.

PMID- 9020211
TI  - Anterior plate instrumentation for disorders of the subaxial cervical spine.
AB  - Anterior cervical plate instrumentation is useful in the maintenance of cervical
      alignment, the prevention of graft extrusion, and the development of late
      deformity as well as potentially avoiding the need for a secondary posterior
      cervical procedure in the setting of cervical trauma. Its role in cervical
      reconstruction after decompression for cervical spondylosis is evolving. The
      definite risks of anterior cervical instrumentation should be considered, that
      is, screw and plate displacement or screw violation of neurologic structures,
      before the implementation of this form of fixation.

PMID- 9020212
TI  - Endoscopic techniques in spinal surgery.
AB  - Minimally invasive techniques are becoming more widespread in the surgical
      subspecialties. Standard open surgical procedures are being modified to become
      less invasive, with the hopes of decreased recovery time, lessened morbidity, and
      ultimately, cost savings. Improvements in technology have allowed the surgeon to
      peer into body cavities and create potential spaces such as the retroperitoneum
      and the neuroforaminal space without the need for traditional extensile surgical
      approach. Improved fiberoptics, light sources, and the advent of the 3-chip
      camera and the 3-dimensional camera have resulted in improvements in
      visualization of the structures surrounding the spine. Although the goals of
      endoscopic surgery are to maintain or improve visualization and minimize the
      approach related trauma, procedures must also prove efficacious and safe with at
      least equivalent results compared with their open surgical counterpart. Not all
      procedures may be applicable to minimally invasive approaches and just because a
      procedure can be done does not mean that it should be done. Laparoscopic and
      thoracoscopic spine procedures also depend on the partnership of the spine
      surgeon with the thoracic or general surgeon with endoscopic experience to ensure
      patient safety. Proficiency in minimally invasive spinal techniques takes
      devotion and does not occur after taking minicourses. Practice with cadaver and
      in vivo models, preceptorship and proctorship training, and ultimately the
      teaching of these techniques in residency and spinal fellowship programs will
      undoubtedly lead to favorable outcomes and reduced medical expenditure.
      Preliminary results are encouraging for endoscopic spinal surgery, but further
      testing of these new techniques against conventional open procedures will be
      important in documenting not only the efficacy of the procedure, but also its
      value in patient satisfaction and cost.

PMID- 9020213
TI  - Technical considerations for electromyographic research on the shoulder.
AB  - This study compared 2 methods of indwelling bipolar electrode insertion. One
      method used a single needle for the insertion of both wire leads, and the second
      method used 2 needles for the independent insertion of both leads at a specified
      interdetection distance. Simultaneous electromyography recordings from the 2
      different electrode configurations were made during the activation of nonfatigued
      supraspinatus and infraspinatus muscles from 10 healthy subjects. Subjects
      performed 6 different isometric contractions at 3 different levels of force
      (100%, 60%, and 30% effort). In this study, the bipolar electrode configuration
      using 2 hypodermic needles for placement of the 2 leads produced superior
      electromyography recordings than did the configuration using a single needle for
      the wire lead insertion. The separated bipolar electrodes produced a
      significantly higher amplitude electromyography signal with less intersubject
      variability and greater partial correlation with force. This study suggests an
      alternative method of bipolar wire electrode placement that results in improved
      signal characteristics and decreased variability of signal acquisition. A
      standardization of wire electromyography examination of the shoulder that
      improves signal characteristics and acquisition ultimately will lead to more
      accurate results with greater clinical use and validity.

PMID- 9020214
TI  - Evaluation of cancellous structure in the distal radius using spectral analysis.
AB  - A preliminary study was conducted to analyze trabecular patterns in digitized
      wrist radiographic images from 68 patients (31 males and 37 females), aged from 7
      to 93 years. The fast Fourier transform was used to perform the spectral analysis
      of the distal radius. Three indices were defined to permit quantification of the
      cancellous structure in terms of the spacing and orientation of bone trabeculae
      (periodicity): a spectral trabecular index, a longitudinal trabecular index, and
      a transverse trabecular index. The spectral trabecular index reflects the
      periodicity of the trabeculae (spacing and orientation), while the other 2
      selectively reflect the periodicity of longitudinally and transversely oriented
      ones. The ratio of the longitudinal and transverse trabecular indices was also
      studied. The shape of the high magnitude frequencies in the spectrum was
      crosslike for all patients, implying a preferentially orthogonal 2-dimensional
      structure for the cancellous bone in the distal end of the radius. The variation
      of the defined trabecular bone indices with age corresponded with the formation
      of bone through infancy and adolescence, reaching a peak in adulthood and gradual
      loss thereafter. This quantification detects structural changes that occur with
      aging and may therefore be useful in the study of osteoporosis.

PMID- 9020215
TI  - Unilateral thoracic facet dislocation.
AB  - A unilateral facet dislocation is an injury classically localized to the cervical
      spine. A series of 3 unilateral thoracic facet dislocations are reported in 2
      adults and 1 child. Each had severe concomitant injuries to the thorax, which
      caused respiratory compromise. On lateral radiographs, all had anterior vertebral
      body translation of less than 20% of the vertebral body width with minor degrees
      of kyphosis. Axial computed tomographic images showed a unilateral empty facet
      sign. All patients were neurologically intact and none had any mechanical pain at
      last followup. The mechanism of injury is flexion distraction with rotational
      force that disrupts the rib cage.

PMID- 9020216
TI  - Mechanisms of low back pain: a neurophysiologic and neuroanatomic study.
AB  - Idiopathic low back pain has confounded health care practitioners for decades.
      The cellular and neural mechanisms that lead to facet pain, discogenic pain, and
      sciatica are not well understood. To help elucidate these mechanisms,
      anesthetized New Zealand white rabbits were used in a series of neurophysiologic
      and neuroanatomic studies. These studies showed the following evidence in support
      of facet pain: an extensive distribution of small nerve fibers and endings in the
      lumbar facet joint, nerves containing substance P, high threshold
      mechanoreceptors in the facet joint capsule, and sensitization and excitation of
      nerves in facet joint and surrounding muscle when the nerves were exposed to
      inflammatory or algesic chemicals. Evidence for pain of disc origin included an
      extensive distribution of small nerve fibers and free nerve endings in the
      superficial annulus of the disc and small fibers and free nerve endings in
      adjacent longitudinal ligaments. Possible mechanisms of sciatica included
      vigorous and long lasting excitatory discharges when dorsal root ganglia were
      subjected to moderate pressure, excitation of dorsal root fibers when the ganglia
      were exposed to autologous nucleus pulposus, and excitation and loss of nerve
      function in nerve roots exposed to phospholipase A2.

PMID- 9020217
TI  - Core decompression for early osteonecrosis of the hip in high risk patients.
AB  - Thirty-four hips (22 patients) with history and physical findings consistent with
      osteonecrosis of the femoral head were evaluated preoperatively by radiographs,
      bone scans and magnetic resonance images. All patients with Stage 0, I, or II
      disease by the Ficat and Arlet classification underwent core decompression using
      the same technique. Osteonecrosis was confirmed histologically in all 34 hips.
      Eighteen of 22 patients had prognostic factors traditionally associated with poor
      outcome including collagen vascular diseases and continued use of steroids.
      Followup averaged 4 years for 18 patients with 29 hips. Four patients died
      secondary to systemic illness. Twelve patients had good or excellent results
      using the Modified Harris Hip Score with 6 patients needing hip arthroplasty. In
      this group of patients previously associated with poor prognosis, no hip
      fractures were seen and 66% good to excellent results were obtained.

PMID- 9020218
TI  - Hip joint forces during load carrying.
AB  - In some diseases affecting only 1 hip joint, it is necessary to keep the contact
      force between femoral head and acetabulum (hip joint force) permanently low at
      the affected side. Six subjects were examined while they were walking and
      carrying a load in 1 or 2 hands. It was determined how the forces in both hip
      joints are influenced by the magnitude of the load and the manner in which it is
      carried. A mathematical model was used to calculate the maximum forces in the
      frontal plane. One subject had instrumented endoprostheses implanted in both
      hips. For him the measured values were slightly higher than the calculated ones,
      but the overall results were similar. Carrying a load on 1 side keeps the force
      constant at the ipsilateral hip joint or even slightly lowers it. At the same
      time, there is a large increase on the opposite side. Carrying 25% of body weight
      with 1 hand causes about 2/3 higher forces in the contralateral joint than on the
      loaded side. If this load is evenly distributed between the 2 sides, both hip
      joint forces increase by 25%. In unilateral load carrying, additional relief of
      the ipsilateral joint can be achieved if the upper body is held upright and the
      loadcarrying arm is abducted, such as when using a large shopping basket.

PMID- 9020219
TI  - Reimplantation of infected hip arthroplasties using bone allografts.
AB  - Twenty-two patients with deep infection of an hip prosthesis received delayed
      reimplantation using bone allografts. Sixteen were done using noncemented
      components and 6 using femoral components that were fixed with antibiotic
      impregnated cement. Bulk allografts were used at the acetabular site in 2
      patients and at the femoral site in 4 patients. Morselized allografts were used
      at the acetabular site in 20 patients and at the femoral site in 10 patients. The
      causative organisms were virulent in 10 hips and low virulent in 12 hips. At an
      average followup of 4 years (range, 2-7 years), 91% of patients were free of
      infection and 73% had a successful functional result. Two had a recurrent
      infection; 1 of them had a pseudomonas infection and another had a methicillin
      resistant Staphylococcal infection. The recurrence of infection tended to be
      higher if the causative organism was virulent. The use of bone allografts at the
      staged reimplantation of the infected hip arthroplasty did not increase the
      incidence of recurrent infection. Both cemented and noncemented reimplantations
      had a successful result in eradicating the infection. However, hybrid
      reimplantation with a cemented femoral component and fixed porous acetabular
      component had a better functional outcome than noncemented reimplantation using
      porous femoral component and nonfixed acetabular component.

PMID- 9020220
TI  - Pelvic lysis and polyethylene wear at 5-8 years in an uncemented total hip.
AB  - The clinical and radiographic results of 160 primary, uncemented porous coated
      total hip replacements performed at 3 teaching hospitals were reviewed. Followup
      was obtained in 132 of 148 (89%) nondeceased patients. The acetabular component
      is a full hemisphere, fabricated of cobalt chrome with a sintered bead coating
      and was implanted with screws in all cases. A 32 mm cobalt chrome femoral head
      was used in all cases. At 2 to 4 years the incidence of pelvic lysis was 0 and no
      acetabular revisions had been performed. At 5 to 8 years followup, 3 of 132 (2%)
      femoral stems had been revised, while on the acetabulum side discrete expansile
      pelvic lytic lesions occurred in 15 cases (11%) with 8 cases (5%) requiring
      revision. Abrasion of the screwhead against the backside of the polyethylene
      liner was seen in all retrieved cases and may have contributed to the development
      of the lytic lesions seen. Use of this uncemented press fit hemispheric
      acetabular components, using adjunctive screw fixation resulted in an
      unacceptably high rate of polyethylene wear and aggressive pelvic lysis. While
      the results on the femoral side were good, the results with this uncemented
      acetabular system did not represent an improvement over previous cemented or
      uncemented acetabular components.

PMID- 9020221
TI  - Wound coverage after modified hip disarticulation using a total adductor
      myocutaneous flap.
AB  - There are several options available for wound coverage after hip disarticulation
      and hemipelvectomy. Standard flaps for closure are not always available due to
      the 3-dimensional extent of the tumor and availability of satisfactory tissue for
      coverage. This article details a new coverage technique after a modified hip
      disarticulation using a total adductor myocutaneous flap in a patient with
      radiation induced osteosarcoma of the femur after Ewing's sarcoma. In this case,
      neither the commonly used posterior flap nor an anterior flap could be used
      because of the location of the tumor and the presence of radiation induced skin
      and soft tissue changes. The total adductor myocutaneous flap allowed for wide
      surgical margins, avoided soft tissue coverage using previously irradiated soft
      tissue flaps, and provided excellent coverage without requiring the use of free
      or pedicle based flaps.

PMID- 9020222
TI  - Chronically injured posterior cruciate ligament: magnetic resonance imaging.
AB  - Magnetic resonance imaging has been said to be highly reliable for diagnosis of
      acute posterior cruciate ligament insufficiency. In the present study, 13
      patients whose posterior cruciate ligament insufficiency had been documented by
      magnetic resonance imaging within 10 weeks of the acute injury were recalled for
      a followup examination and magnetic resonance imaging. The followup interval
      ranged from 5 months to 4 years. In only 23% of the cases did the posterior
      cruciate ligament still appear discontinuous on followup magnetic resonance
      imaging. In the remaining 77%, the posterior cruciate ligament was continuous
      from tibia to femur, although it appeared abnormally arcuate or hyperbuckled.
      Conventional interpretation of these magnetic resonance images would suggest that
      the posterior cruciate ligament had healed. Nevertheless, by clinical examination
      results, these same patients all were judged to have posterior cruciate ligament
      insufficiency. Thus, it was concluded that although magnetic resonance imaging
      may be reliable for evaluation of acute posterior cruciate ligament injury,
      magnetic resonance imaging findings should not be used to infer functional status
      in chronic cases.

PMID- 9020223
TI  - Fractures in very low birth weight infants with rickets.
AB  - A syndrome in very low birth weight premature infants weighing less than 1500 g
      is evidenced by developmental nutritional rickets and fractures at 75 days of
      age. In a review conducted over 42 months, 247 very low birth weight cases were
      identified. Rickets was diagnosed in 96 (39%) infants whose mean age was 50 days
      and fractures were diagnosed in 26 (10.5%) infants whose mean age was 75 days.
      These 26 infants experienced 98 fractures: 10 humerus, 13 radius, 8 ulna, 4
      metacarpal, 3 clavicle, 54 ribs, 5 femur, and 1 fibula. Risk factors included
      hepatobiliary disease, total parenteral nutrition, diuretic therapy, physical
      therapy with passive motion, and chest percussion therapy. With early
      recognition, metabolic therapy and splinting, not casting, are appropriate
      treatments.

PMID- 9020224
TI  - Orthopaedic long term aspects of bladder exstrophy.
AB  - This study evaluates long term orthopaedic aspects of children with bladder
      exstrophy who were operated on using different techniques and at different ages.
      Data were accumulated from 20 patients with an age range of 2 to 29 years
      (average, 13 years). Fourteen patients underwent pelvic osteotomy. Interviews and
      physical examinations confirmed that, in the long term, children with classical
      bladder exstrophy do not have significant orthopaedic problems or disability,
      whether or not they underwent pelvic osteotomy. Radiographic imaging showed
      normal hip joint configuration with marked pubic diastasis. There were no
      clinical problems associated with the diastasis. Pelvic computed tomography
      studies in 7 patients showed marked remodeling of the femora and acetabula.
      Radiographs of the spine showed a curve in 7 (47%) of the patients, but in only 3
      cases was the curve larger than 10 degrees. Pelvic osteotomy is indicated during
      surgical correction of bladder exstrophy to facilitate closure of the abdominal
      wall to prevent postoperative wound dehiscence and possibly achieve better
      urinary control in older age. However, there is no clear indication for pelvic
      osteotomy from an orthopaedic point of view.

PMID- 9020225
TI  - Tuberculosis of the long bone in children.
AB  - From 1985 to 1994, there were 24 cases of long bone solitary tuberculosis. They
      were 18 boys and 6 girls with an average age of 18 months. All of the patients
      were treated by open biopsy and curettage and antituberculosis therapy (isoniazid
      and rifampin) for 6 months. Two patients had incomplete administration of the
      drug therapy. The lesions were in the metaphysis. Epiphyseal involvement was not
      significant. The tuberculin skin test was negative in 3 children and the culture
      was negative in 17 cases. After 2 years and 8 months' followup, there was
      radiographic evidence of good bone remodeling. Although there uncommonly is not a
      delay in diagnosis of skeletal tuberculosis despite prolonged symptoms,
      diagnostic biopsy with curettage of the lesion is indicated for isolated lesions,
      especially when the diagnosis is in doubt. It is significant that surgical
      debridement can shorten the duration of antituberculosis therapy and lead to
      improved results.

PMID- 9020226
TI  - Analysis of giant cell tumor of bone with pulmonary metastases.
AB  - The authors reviewed 6 cases of giant cell tumor of bone with pulmonary
      metastases, analyzed the growth rate of the metastases, and performed flow
      cytometry on paraffin blocks from primary and metastatic lesions. Surgery on the
      pulmonary metastases was done in 3 cases. Chemotherapy was administered in all 6
      cases. If the doubling time of the pulmonary metastases was more than 80 days,
      the case was considered to be slow growing or in regression. However, if the
      doubling time was approximately 30 days, the prognosis was poor. The cases were
      divided into 3 types according to the prognosis. After chemotherapy
      (cyclophosphamide), the pulmonary metastases decreased in size in 2 cases. In 2
      other cases, the metastases were slow growing, and the remaining 2 patients died
      early. Flow cytometric analysis was performed on primary and metastatic lesions,
      which showed a diploid pattern in most cases, but a tetraploid pattern in 1
      recurrent case. Pulmonary metastatic lesions displayed a diploid pattern in 4
      cases from which materials were taken either at surgery or autopsy.

PMID- 9020227
TI  - Extraarticular pigmented villonodular synovitis of the shoulder: a case report.
AB  - A rotator cuff tear was diagnosed in a 57-year-old woman based on physical
      examination and magnetic resonance imaging studies. At operation, an abnormal
      bursal lesion also was found. The lesion was completely extraarticular and was
      identified histologically as pigmented villonodular synovitis. The patient was
      treated with complete bursectomy and repair of the rotator cuff tear and remains
      asymptomatic 21 months after operation. Pigmented villonodular synovitis is a
      condition characterized by cell proliferation and deposition of hemosiderin into
      the lining tissues of joints, tendons, and bursae. The extraarticular form of
      pigmented villonodular synovitis is extremely rare and usually represents an
      extension of a primary intraarticular process. Only a few cases have been
      reported in which the lesion was found exclusively outside the joint with no
      intraarticular segment. In reviewing the literature, no case of exclusively
      extraarticular pigmented villonodular synovitis of the shoulder was found. The
      sequelae of extraarticular pigmented villonodular synovitis are poorly
      understood, but this lesion can be locally invasive, and if left untreated, may
      destroy surrounding tissues. Therefore, early diagnosis and treatment are
      important for optimal results.

PMID- 9020228
TI  - Treatment of open tibial fractures with primary suture and Ilizarov fixation.
AB  - Thirty-two open tibial fractures were treated by irrigation, debridement,
      antibiotic therapy, primary closure when possible, and fixation with Ilizarov
      device. In the Gustilo classification, 11 were Grade I, 10 Grade II, 8 Grade
      IIIA, and 3 were Grade IIIB. No Grade IIIC fractures were treated in the period
      studied. Fifteen were in patients with multiple trauma, and in 17 patients the
      fracture was a single injury. All fractures healed with good anatomic alignment,
      except for 1 with 5 degrees angulation and another with 1-cm shortening. The
      healing time was 21.9 weeks in the single injury and 25.7 weeks in the patients
      with multiple trauma. Eleven patients had pin tract infection, and in 4 the pin
      had to be replaced. One patient had dermatitis near the fracture site. This
      treatment of open tibial fractures proved to be successful for anatomic
      restoration of the tibia and had a low complication rate. Primary closure should
      be considered a possible method of treatment in Types I to IIIA open fractures,
      together with the Ilizarov external fixator, if the wound edges can be
      approximated easily with no tension at the suture line.

PMID- 9020229
TI  - Comparative study of monoclonal antibody scan in diagnosing orthopaedic
      infection.
AB  - When clinical data are insufficient to diagnose infection of bone or joints,
      nuclear scanning becomes crucial in making an accurate diagnosis. The efficacy of
      (99m)technetium antigranulocyte monoclonal antibody Fab' fragment (LeukoScan) is
      prospectively compared with (111)indium white blood cell and (99m)technetium
      methylene diphosphonate bone scans in 74 patients with suspected musculoskeletal
      infections. They were grouped according to site of suspected infection: 33 long
      bones, 23 prosthetic joints, and 18 diabetic feet. Sixty-two of these 74 patients
      had surgical verification with histopathology or culture. The remaining 12
      patients had clinical followup as proof of absence of infection. The overall
      sensitivity of LeukoScan, (111)indium white blood cell, and (99m)technetium
      methylene diphosphonate bone scans was 93%, 85% and 92%, respectively.
      Specificity was 89%, 75% and 52%, and accuracy was 90%, 79% and 74%,
      respectively. The conclusion from this study is that LeukoScan is more accurate
      in detecting osteomyelitis, with better sensitivity and specificity in prosthetic
      joints. Compared with (111)indium white blood cell scans, LeukoScan++ gives
      superior images, and results are obtained in 1 to 6 hours without biohazard risk
      from handling blood products.

PMID- 9020230
TI  - Delayed primary wound closure in upper extremity soft tissue infections.
AB  - Health care costs for inpatient care have been escalating. Homeless and indigent
      patients may be unable to have access to clean toilet facilities to perform
      adequate wound care. Evaluation of delayed primary closure of upper extremity
      soft tissue infections after incision and drainage in 34 patients was done.
      Patients were discharged at an average of 8.3 days (range, 5-21 days). This is 11
      days less than the reported average granulation time for wounds to heal. No
      patient required readmission for surgery, wound care, or intravenous antibiotics.
      The authors' institution charges a rate of $2800 per patient day. A potential
      savings of $1,047,200 was realized.

PMID- 9020231
TI  - Nationwide survey of bone grafting performed from 1980 through 1989 in Japan.
AB  - Nationwide surveys were conducted in 1985 and 1989 on the status of bone grafting
      performed in Japan. At the first survey, questionnaires were sent to 527
      hospitals, with 218 responding. Of 26,800 bone grafts performed, 96.4% were
      autografts, and the remaining 3.6% were allografts and xenografts. Most
      allografts were bone chip grafts (85%), followed by massive bone grafts excluding
      osteoarticular grafts (14%). Osteoarticular allografts and whole bone allografts
      composed only 0.4% and 0.5% of the total, respectively. At the second survey,
      questionnaires were sent to 2053 hospitals, with 967 responding. The use of
      synthetic bone substitutes and bone grafts was investigated in the second survey.
      Of 87,994 bone grafts performed, 94.3% were autografts, 3.2% were synthetic bone
      substitutes, 1.9% were banked bone allografts, 0.4% were fresh allografts, and
      0.2% were xenografts. Most of all grafts were bone chip grafts (57.1%), followed
      by massive bone grafts excluding osteoarticular grafts (40.3%). Osteoarticular
      grafts and whole bone grafts accounted for only 0.3% and 2.3% of the totals,
      respectively. Although the number of patients requiring bone grafts increased
      yearly, bone allografts were not widely used in Japan.

PMID- 9020232
TI  - Remodeling of allogeneic and autogenous patellar tendon grafts in rats.
AB  - The differences in remodeling among frozen allografts, frozen autografts, and
      fresh autografts were investigated using a patellar tendon transplantation model
      in 2 different strains of rats. In this study, isografting (transplantation among
      the same strain inbred animals) was adopted as an autograft model. This method
      makes it possible to set up a frozen autograft model. Evaluation included
      mechanical properties determined during tensile failure tests, cross sectional
      area, histologic findings, and collagen fibril distribution. Recipient rats were
      euthanized at 4, 8, 12, and 24 weeks after transplantation (n = 5, in each group
      and in each period). The frozen allografts showed significantly less tensile
      strength than did the frozen autografts at 4 weeks, but this difference was
      transient and diminished by 8 weeks. The tensile strength of the fresh autografts
      was significantly greater than that of the frozen autografts at 8 weeks or the
      frozen allografts at 8 and 12 weeks. It was suggested that freeze thawing has
      adverse effects on the remodeling of fresh autografts in this extraarticular
      graft model. The cross sectional area for each type of graft at each
      posttransplantation period was about twice as large as that before
      transplantation. The collagen fibril profile of the frozen allografts was similar
      to that of the frozen autografts. However, the fresh autografts showed a greater
      number of large diameter fibrils and a lesser number of small diameter fibrils
      than did the other 2 frozen groups.

PMID- 9020233
TI  - In situ levels of intracellular Ca2+ and pH in avian growth plate cartilage.
AB  - Interactions with the extracellular matrix, accumulation of Ca2+, formation of
      matrix vesicles, and regulation of tissue pH by growth plate chondrocytes all
      appear to be vital to endochondral calcification. Thus, the activities of Ca2+
      and H+ ions in these cells, while still embedded in their organic matrix, are of
      great interest. Using laser confocal imaging and sensitive Ca2+ (Indo 1) and pH
      (BCECF) probes, cellular Ca2+ and pH were analyzed in thin sections of freshly
      isolated cartilage. Mean values of cytosolic Ca2+ in cells from the various zones
      of the growth plate were quite similar, but levels in individual cells and
      subcellular compartments varied significantly. Ca2+ was elevated intensely near
      the periphery of cells in the zones of maturation and hypertrophy, and many Ca2+
      rich particles were seen in the matrix near these cells. Levels of Ca2+ within
      the cells varied with time. In the proliferative region, cyclical increases and
      decreases in Ca2+ were seen, but there was little shedding of Ca2+ rich
      particles. However, after repeated Ca2+ cycling, in the zones of maturation and
      hypertrophy, Ca2+ rich particles were shed from the cell surface, forming what
      appeared to be matrix vesicles. Intracellular pH levels also varied significantly
      within the chondrocytes and between the cells and zones. Numerous focal
      elevations in pH (> 8.0) were seen in central regions of the maturing and early
      hypertrophic cells, with lower pH (6.5-7.2) near the cell periphery of the late
      hypertrophic and calcifying cells. This pattern of cytoplasmic alkalinization and
      subsequent acidification appears to contribute to loading of Ca2+ and Pi into
      matrix vesicles during their formation by the chondrocytes.

PMID- 9020234
TI  - Biomechanical evaluation of tension band placement for the repair of olecranon
      fractures.
AB  - Displaced transverse fractures of the olecranon commonly are treated by open
      reduction and internal fixation using the AO tension band wiring technique.
      Reports that the AO technique has a tendency to open the fracture site at the
      articular surface prompted Rowland and Burkhart to modify placement of the
      tension band. The present study tested the hypothesis that the modified wire
      placement provides static compression anteriorly, and hence better reduction at
      the articular surface of the fracture, than the AO technique under static
      conditions. Transverse olecranon fractures were created on 8 pairs of fresh
      cadaveric arms. One ulna of each pair was repaired using the modified wire
      placement, whereas the contralateral ulna was repaired using the AO technique.
      The humerus was driven into the trochlear fossa of each ulna using a
      servohydraulic testing machine while a force transducer and video system measured
      the applied force and gap formation at the articular surface of the fracture.
      Because the static behavior of the fixations was tested, no muscle forces were
      included. Results indicated no significant differences in yield loads or
      stiffness values between the 2 techniques. Based on the results of this static
      study, the modified wire placement does not provide increased stability of
      fracture fixation compared with the AO tension band wiring technique.

PMID- 9020235
TI  - Thigh mass in a 75-year-old man [clin conference].

PMID- 9020236
TI  - Biomechanical control of knee alignment: some insights from a new paradigm.
AB  - A chondral growth force response curve suggests how longitudinal bone growth at
      growth plates responds to compression loads. Between zero load and some limit,
      increasing loads increase growth. Above that limit, further increases in
      compression can decrease growth, and large enough compression loads can stop it.
      In the valgus-varus sense, in a child's knee these responses would tend to make
      its growth plates and the joint align perpendicularly to the time-averaged
      compression loads on them and tend to correct small malalignments but make large
      malalignments become worse. Combined with effects of the regional acceleratory
      phenomenon, in children these responses can also explain some cases of
      postfracture knee valgus and its subsequent spontaneous correction.

PMID- 9020237
TI  - Quo vadis? A dietitian looks at the state of dietetics today.

PMID- 9020238
TI  - Expanding roles for dietitians working with persons with developmental
      disabilities.

PMID- 9020239
TI  - Lack of effect of sleep on energy expenditure and physiologic measures in
      critically ill burn patients.
AB  - OBJECTIVE: Energy expenditure measurements, performed while patients are in
      standardized resting conditions, are often used as an indicator of care by which
      to evaluate the adequacy of nutrition support regimens. Little attention has been
      directed toward examining potential errors incurred by deriving daily energy
      needs based on a single 15- to 20-minute measurement. This study was designed to
      differentiate energy expenditure during periods of sleep (defined as time spent
      in any of the standard sleep stages) and wakefulness in pediatric burn patients.
      DESIGN: Twenty-four-hour indirect calorimetry, polysomnography, and physiologic
      assessments (mean arterial pressure, heart rate, body temperature, oxygen
      saturation, and respiratory rate) were conducted simultaneously in 14 patients,
      who were thermally injured and tracheally intubated, for a total of 45 24-hour
      intervals. SUBJECTS: Mean age of the patients was 10.8+/-1.2 years. Mean total
      body surface area of the injury was 55.7+/-4.7%, and mean full-thickness burn was
      48.8+/-6.0%. STATISTICAL ANALYSES PERFORMED: A nested general linear analysis of
      variance model was used to evaluate the association between sleep, wakefulness,
      and energy needs; adjustments were made for postburn day and multiple test runs
      per patient. RESULTS: On average, subjects slept 699+/-46 minutes/day. They
      experienced a large number of awakenings from sleep (mean=53+/-6.3 awakenings per
      24 hours). Patients had mean energy expenditure of 2,529+/-396 kcal/day while
      awake and 2,360+/-291 kcal/day while asleep, and these mean values did not differ
      significantly. No differences in physiologic measurements during the awake and
      sleep states were found. APPLICATIONS: There appears to be little difference in
      the metabolism of seriously injured burn patients while asleep and while awake.
      The study deemphasizes the importance of performing indirect calorimetry at rest
      in critically ill pediatric burn patients, and it supports the extrapolation of
      daily energy expenditure from a 15- to 20-minute steady-state measurement
      obtained during either sleep or wakefulness.

PMID- 9020240
TI  - Cross-validation of prediction equations for resting energy expenditure in young,
      healthy children.
AB  - OBJECTIVE: To examine the accuracy of several prediction equations for resting
      energy expenditure (REE) in children. DESIGN: REE was measured in 113 prepubertal
      children (60 girls and 53 boys aged 3.9 to 7.8 years old, weighing 14.7 to 30.0
      kg) using indirect calorimetry and compared with values estimated from the
      prediction equations of Altman and Dittmer, The Food and Agriculture
      Organization/World Health Organization/United Nations University (FAO/WHO/UNU),
      Maffeis et al, and Harris and Benedict. STATISTICAL ANALYSIS: Measured REE (MREE)
      was compared with predicted REE (PREE) by means of regression analysis.
      Prediction equations were considered accurate if the regression of MREE vs PREE
      was not significantly different from the line of identity (slope=1.0;
      intercept=0). Precision was assessed by the multiple correlation coefficient of
      the regression of MREE vs PREE. RESULTS: MREE was 938+/-119 kcal/day, and PREE
      was 1,057+/-224 kcal/day for the Altman and Dittmer equations, 956+/-84 kcal/day
      for the FAO/WHO/UNU equations, 948+/-64 kcal/day for the equations of Maffeis et
      al, and 954+/-102 kcal/day for the Harris-Benedict equations. The regression of
      MREE vs PREE was significantly different from the line of identity for all
      prediction equations except the FAO/WHO/UNU equations (slope=0.96, P=.735;
      intercept=-15 kcal/day, P=.885 for girls and slope=1.08, P=.635; intercept=-62
      kcal/day, P=.635 for boys). None of the equations was precise for MREE vs PREE
      (for all, R2<.6). For the FAO/WHO/UNU equations, less than half of the
      predictions were within +/-50 kcal/day but 99% were within 200 kcal/day.
      CONCLUSION: Most prediction equations for REE in children do not accurately or
      precisely estimate REEs. The exception is the FAO/WHO/UNU equations, which are
      reasonably accurate and precise for practical purposes.

PMID- 9020241
TI  - Development and evaluation of a computer-based system for dietary management of
      hyperlipidemia.
AB  - OBJECTIVE: To describe the development of a computer-based system for dietary
      management of hyperlipidemia and to evaluate its efficacy for lowering plasma
      cholesterol level. DESIGN: Using a stepwise approach, we developed and tested a
      three-part self-management system in five consecutive clinical studies. Each
      study assessed plasma cholesterol levels before and after dietary intervention
      using the system. These studies enabled progressive refinement of (a) a food
      frequency questionnaire used to assess food intake in the preceding month; (b)
      computer-generated progress reports, based on questionnaire responses, offering
      dietary change subgoals and strategies for change; and (c) a dietary workbook
      providing detailed information on how to achieve goals. SUBJECTS/SETTING: Persons
      with hyperlipidemia (n=814) were enrolled from worksite and clinical settings in
      the San Francisco Bay area of California. The attrition rate after randomization
      was 5%. INTERVENTION: Elements of the dietary intervention evolved in response to
      the results of five clinical studies. In each study, patients underwent a form of
      baseline assessment of dietary intake followed by counseling/instruction by
      various means. Follow-up dietary assessments were provided at specific intervals
      to facilitate subjects' progress toward their dietary goals. A dietary workbook
      provided the detailed instruction required to implement the recommendations
      contained in the periodic progress reports. STATISTICAL ANALYSES PERFORMED:
      Changes in plasma cholesterol level were measured by paired and unpaired t tests.
      The relationship between the reported reduction in dietary fat and cholesterol
      level assessed by food frequency questionnaires and the directly measured change
      in plasma cholesterol level was measured by multiple linear regression. RESULTS:
      The three major elements of the final computerized system (food frequency
      questionnaires, computer-generated progress reports, and dietary workbook) were
      developed and refined in the course of the five clinical studies. Reductions in
      total plasma cholesterol level of 5.0% to 6.5% achieved by participants in all
      five studies were consistent with self-reported reductions in intake of dietary
      saturated fat and cholesterol. Therefore, the computerized self-management system
      appears to be an effective tool for reducing plasma cholesterol levels.
      APPLICATIONS/CONCLUSIONS: A computer-based system for dietary self-management of
      hyperlipidemia, implemented by mail, was effective in short-term studies. This
      self-management system can potentially provide health-promoting services to large
      numbers of people at low cost.

PMID- 9020242
TI  - A low-fat diet supplemented with monounsaturated fat results in less HDL-C
      lowering than a very-low-fat diet.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of a very-low-fat
      diet with a low-fat diet supplemented with monounsaturated oil on plasma lipid
      levels in subjects with hypercholesterolemia. DESIGN: The 8-week study was
      divided into one 2-week baseline diet and two 3-week intervention periods in a
      randomized crossover design. SETTING: The study was conducted in an outpatient
      setting at the Deakin Institute of Human Nutrition, Deakin University, Geelong,
      Australia. SUBJECTS: Twenty-four free-living subjects with hypercholesterolemia
      participated in and completed the study. INTERVENTION: After a 2-week baseline
      period of a self-selected diet, subjects were assigned to one of two dietary
      interventions: a very-low-fat (10% of energy from fat), high-carbohydrate diet or
      a low-fat (26% of energy from fat) diet supplemented with olive oil and an olive
      oil-based margarine. MAIN OUTCOME MEASURES: Lipid measurements included total
      cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, and triglyceride concentrations. Plasma cholesteryl esters were
      measured to monitor compliance. STATISTICAL ANALYSES: A paired t test was used to
      assess differences between treatment periods for each subject. The dependence of
      the difference between treatment periods on the covariates of age, sex, initial
      cholesterol concentration, and energy intake was analyzed using repeated measures
      and analysis of covariance. RESULTS: The low-fat diet supplemented with
      monounsaturated fat resulted in significantly less high-density lipoprotein
      cholesterol lowering than the very-low-fat diet (P=.005). Both interventions
      resulted in significant reductions in both low-density lipoprotein cholesterol
      and total cholesterol compared with the baseline diet. APPLICATIONS: This study
      suggests that a low-fat diet enriched with olive oil provides advantages over a
      very-low-fat diet in the control of serum lipoproteins among persons with
      hypercholesterolemia.

PMID- 9020243
TI  - Obstacles to nutrition labeling in restaurants.
AB  - OBJECTIVE: This study determined the major obstacles that foodservices face
      regarding nutrition labeling. DESIGN: Survey questionnaire was conducted in May
      1994. In addition to demographic questions, the directors were asked questions
      addressing willingness, current practices, and perceived obstacles related to
      nutrition labeling. SUBJECTS/SETTING: Sixty-eight research and development
      directors of the largest foodservice corporations as shown in Restaurants &
      Institutions magazine's list of the top 400 largest foodservices (July 1993).
      STATISTICAL ANALYSES PERFORMED: P tests were used to determine significance
      within a group for the number of foodservices that were currently using nutrition
      labeling, perceived impact of nutrition labeling on sales, and perceived
      responsibility to add nutrition labels. Regression analysis was used to determine
      the importance of factors on willingness to label. RESULTS: Response rate was
      45.3%. Most companies were neutral about their willingness to use nutrition
      labeling. Two thirds of the respondents were not currently using nutrition
      labels. Only one third thought that it was the foodservice's responsibility to
      provide such information. Several companies perceived that nutrition labeling
      would have a potentially negative effect on annual sales volume. Major obstacles
      were identified as menu or personnel related, rather than cost related. Menu
      related obstacles included too many menu variations, limited space on the menu
      for labeling, and loss of flexibility in changing the menu. Personnel-related
      obstacles included difficulty in training employees to implement nutrition
      labeling, and not enough time for foodservice personnel to implement nutrition
      labeling. APPLICATIONS: Numerous opportunities will be created for dietetics
      professionals in helping foodservices overcome these menu- or personnel-related
      obstacles.

PMID- 9020244
TI  - A nutritional rehabilitation program for persons with severe physical and
      developmental disabilities.
AB  - Our purpose was to design and implement a nutritional rehabilitation program for
      persons with severe developmental disabilities who resided in a long-term-care
      facility or a group home. We used weight for height (WH) to classify residents of
      both facilities into three groups: group 1 (n=32), WH less than 5th percentile (Z
      scores < or = -1.650), goal=gain weight; group 2 (n=21), WH between the 5th and
      85th percentile (Z scores ranging from -1.645 to +1.030), goal=maintain present
      rate of weight gain; and group 3 (n=8), WH greater than 85th percentile (Z scores
      > or = +1.036), goal=slow down rate of weight gain. The challenge in all groups
      was to bring about these changes without increasing the quantity of food (as
      assessed by 3-day food records) fed to the residents and to increase their fluid
      intake. For each subject, the project dietitian developed individualized menus
      that specified quantities and consistencies of food. Foodservice delivery was
      changed to a centralized system in the long-term-care facility to allow for
      closer control of the subjects' intake. A dietitian monitored the program with
      biweekly visits to the wards and frequent consultation with staff. Only a limited
      increase in fluid intake was noted; however, after 6 months of the program, the
      other goals were met. Our results suggest that nutritional rehabilitation of
      residents with developmental disabilities is enhanced by the involvement of a
      dietitian.

PMID- 9020246
TI  - Dietitians can and should communicate with older adults with hearing and vision
      impairments and communication disorders.

PMID- 9020245
TI  - Folate nutrition and older adults: challenges and opportunities.
AB  - Folate fortification of bread and grains has been directed to prevent neural tube
      birth defects. Research has also challenged previous concepts of folate
      nutritional status and suggested that folate may play a role in reducing the risk
      of vascular disease. Although folate status of many elderly people is adequate
      according to traditional, hematologic criteria, some elderly persons have
      elevated blood concentrations of the metabolite homocysteine, which indicates
      subclinical deficiency of folate or vitamin B-12. Higher homocysteine
      concentrations, even within the normal range, are associated with increased risk
      of vascular disease. Elderly people with better folate and vitamin B-12 status
      have lower homocysteine concentrations and may have lower risk for vascular
      disease. Although the new folate fortification rules provide the benefit of
      increasing folate in the food supply, they could be a risk for the elderly
      because excess folate intake can mask vitamin B-12 deficiency, thereby delaying
      diagnosis. Elderly people have a higher prevalence of vitamin B-12 deficiency as
      a result of absorption problems. Those deficient in vitamin B-12 should be
      treated to prevent irreversible neurologic damage. Modern approaches to screening
      the elderly include using higher cutoff points for serum vitamin B-12 and
      obtaining blood concentrations of the metabolite methylmalonic acid, which is
      elevated in deficiency of vitamin B-12 but not folate. To examine current folate
      intake and food sources, food frequency questionnaires were administered to 308
      elderly volunteers aged 65 to 94 years. Mean (+/-standard error) folate intake
      from food was 299.6+/-5.8 microg/day. Supplements (median dose=400 microg/day)
      were consumed by 47% of participants. Only 3.2% of the sample had total folate
      intake greater than 1,000 microg/day, the recommended upper limit, and these were
      taking high-dose folate supplements (> or = 800 microg/day). Breakfast cereals
      provided 25.6% of folate intake; vegetables, 23.2%; fruit, 20.8%; refined
      breads/grains, 6.7%; dark bread, 5.0%; legumes/nuts, 5.9%; dairy products, 5.8%;
      meat/poultry/fish/eggs, 5.1%; other, 1.9%. Mean folate intake would increase
      16.5% if enriched bread and grains were fortified. Such fortification could help
      some persons to lower serum homocysteine concentration and vascular disease risk.
      Dietitians should be aware of modern protocols for screening the elderly for
      vitamin B-12 deficiency.

PMID- 9020247
TI  - Multimethod training increases portion-size estimation accuracy.

PMID- 9020248
TI  - Caffeine content of fountain and private-label store brand carbonated beverages.

PMID- 9020249
TI  - Acute hemolysis related to consumption of fava beans: a case study and medical
      nutrition therapy approach.

PMID- 9020250
TI  - Position of the American Dietetic Association: food and water safety.

PMID- 9020251
TI  - Position of the American Dietetic Association: nutrition in comprehensive program
      planning for persons with developmental disabilities.

PMID- 9020253
TI  - Report on the 1995 membership database of the American Dietetic Association.

PMID- 9020254
TI  - Geriatricians want better end-of-life care.

PMID- 9020255
TI  - Physician, nurse relief workers killed in Rwanda.

PMID- 9020256
TI  - Rx: traveling museum exhibit to be taken ad lib.

PMID- 9020257
TI  - From the Centers for Disease Control and Prevention. Evaluation of safety devices
      for preventing percutaneous injuries among health-care workers during phlebotomy
      procedures--Minneapolis-St Paul, New York City, and San Francisco, 1993-1995.

PMID- 9020258
TI  - From the Centers for Disease Control and Prevention. Evaluation of blunt suture
      needles in preventing percutaneous injuries among health-care workers during
      gynecologic surgical procedures--New York City, March 1993-June 1994.

PMID- 9020260
TI  - Vascular access in patients receiving hemodialysis.

PMID- 9020259
TI  - From the Centers for Disease Control and Prevention. Outbreaks of pneumococcal
      pneumonia among unvaccinated residents in chronic-care facilities--Massachusetts,
      October 1995, Oklahoma, February 1996, and Maryland, May-June 1996.

PMID- 9020261
TI  - Vascular access in patients receiving hemodialysis.

PMID- 9020262
TI  - Vascular access in patients receiving hemodialysis.

PMID- 9020263
TI  - Crack vs inhaled cocaine and sentencing.

PMID- 9020264
TI  - Crack vs inhaled cocaine and sentencing.

PMID- 9020265
TI  - Crack vs inhaled cocaine and sentencing.

PMID- 9020266
TI  - More on screening for mild thyroid failure.

PMID- 9020267
TI  - Reducing rates of diagnostic imaging.

PMID- 9020268
TI  - Psychiatric care and patient confidentiality.

PMID- 9020269
TI  - Prognostic implication of creatine kinase elevation following elective coronary
      artery interventions.
AB  - OBJECTIVE: To determine the prognostic significance of creatine kinase (CK)
      elevation following elective percutaneous transluminal coronary angioplasty
      (PTCA). DESIGN: Retrospective cohort study. SETTING: Tertiary care referral
      center. SUBJECTS: A total of 253 consecutive patients with total CK and CK-MB
      fraction (CK-MB) elevation (case patients) and 120 patients without CK elevation
      (controls). Control patients had undergone interventions during the same month
      and year using the same devices. MAIN OUTCOME MEASURES: In-hospital and late
      cardiac mortality, subsequent myocardial infarction, and the combined end point
      of cardiac mortality or myocardial infarction. RESULTS: Patient groups were
      similar with respect to age, sex, extent of coronary artery disease, left
      ventricular function, number of lesions treated by PTCA, and mean duration of
      follow-up (>3.5 years). Cardiac mortality was significantly greater (P=.02) for
      patients with CK elevation after PTCA. When patients were categorized according
      to peak CK elevation, cardiac mortality differed significantly among patient
      groups (P=.007), with increased cardiac mortality observed for patients with high
      (>3.0 times normal) and intermediate (1.5 to 3.0 times normal) CK elevations. In
      multivariate analyses, higher peak CK and lower ejection fraction were the most
      important predictors of increased cardiac mortality (both, P<.001); the relative
      risk for cardiac mortality was 1.05 (95% confidence interval, 1.03-1.08) per 100
      U/L increment increase in CK. CONCLUSIONS: Creatine kinase elevation following
      elective PTCA is associated with increased late cardiac mortality. This increase
      in cardiac mortality is independent of clinical variables, severity of heart
      disease, coronary artery lesion characteristics, interventional devices, and
      procedural outcomes. Even patients with lesser degrees of CK elevation are at
      significantly increased risk for late cardiac death.

PMID- 9020270
TI  - Fifteen-year survival in prostate cancer. A prospective, population-based study
      in Sweden.
AB  - OBJECTIVE: To describe the natural history of initially untreated early-stage
      prostate cancer. A key secondary objective was to calculate long-term survival
      rates by stage, grade, and age at diagnosis. DESIGN: Prospective cohort study.
      SETTING: Population-based in 1 county of Sweden, without screening for prostate
      cancer. PATIENTS: A group of 642 patients with prostate cancer of any stage,
      consecutively diagnosed between 1977 and 1984 at a mean age of 72 years with
      complete follow-up to 1994. MAIN OUTCOME MEASURES: Proportion of patients who
      died from prostate cancer, and 15-year survival (with 95% confidence interval
      [CI]), corrected for causes of death other than prostate cancer. RESULTS: In the
      entire cohort, prostate cancer accounted for 201 (37%) of all 541 deaths. Among
      300 patients with a diagnosis of localized disease (T0-T2), 33 (11%) died of
      prostate cancer. In this group, the corrected 15-year survival rate was similar
      in 223 patients with deferred treatment (81%; 95% CI, 72%-89%) and in 77 who
      received initial treatment (81%; 95% CI, 67%-95%). The corrected 15-year survival
      was 57% (95% CI, 45%-68%) in 183 patients with locally advanced cancer (T3-T4)
      and 6% (95% CI, 0%-12%) in those 159 who had distant metastases at the time of
      diagnosis. CONCLUSION: Patients with localized prostate cancer have a favorable
      outlook following watchful waiting, and the number of deaths potentially
      avoidable by radical initial treatment is limited. Without reliable prognostic
      indicators, an aggressive approach to all patients with early disease would
      entail substantial overtreatment. In contrast, patients with locally advanced or
      metastatic disease need trials of aggressive therapy to improve their poor
      prognosis.

PMID- 9020271
TI  - Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus
      in women.
AB  - OBJECTIVE: To examine prospectively the relationship between glycemic diets, low
      fiber intake, and risk of non-insulin-dependent diabetes mellitus. DESIGN: Cohort
      study. SETTING: In 1986, a total of 65173 US women 40 to 65 years of age and free
      from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed
      dietary questionnaire from which we calculated usual intake of total and specific
      sources of dietary fiber, dietary glycemic index, and glycemic load. MAIN OUTCOME
      MEASURE: Non-insulin-dependent diabetes mellitus. RESULTS: During 6 years of
      follow-up, 915 incident cases of diabetes were documented. The dietary glycemic
      index was positively associated with risk of diabetes after adjustment for age,
      body mass index, smoking, physical activity, family history of diabetes, alcohol
      and cereal fiber intake, and total energy intake. Comparing the highest with the
      lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence
      interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a
      global dietary insulin demand) was also positively associated with diabetes (RR=
      1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely
      associated with risk of diabetes when comparing the extreme quintiles (RR=0.72,
      95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a
      low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI,
      1.14-5.51) when compared with a low glycemic load and high cereal fiber intake.
      CONCLUSIONS: Our results support the hypothesis that diets with a high glycemic
      load and a low cereal fiber content increase risk of diabetes in women. Further,
      they suggest that grains should be consumed in a minimally refined form to reduce
      the incidence of diabetes.

PMID- 9020272
TI  - The prevalence of serum antibody to human herpesvirus 8 (Kaposi sarcoma
      associated herpesvirus) among HIV-seropositive and high-risk HIV-seronegative
      women.
AB  - OBJECTIVE: To determine the prevalence of human herpesvirus 8 (HHV-8)
      seropositivity among women who are known to be infected with human
      immunodeficiency virus type 1 (HIV-1) or who are at high risk for HIV infection.
      DESIGN: A cross-sectional and blinded study of the prevalence of serological
      reactivity to HHV-8 infection as determined by an indirect immunofluorescence
      assay using nuclei from cells latently infected with HHV-8. Data and specimens
      were collected at baseline assessments of a longitudinal natural history cohort
      study. SETTING: Four San Francisco Bay Area outpatient HIV specialty clinics
      participating in the cohort study. PATIENTS: A total of 387 participants in the
      Women's Interagency HIV Study whose HIV infection status was documented and serum
      was available in a local specimen repository. MAIN OUTCOME MEASURE: Serological
      reactivity to HHV-8. RESULTS: Serological reactivity to latent HHV-8 antigens was
      uncommon among study participants: 13 (3.4%) demonstrated serum antibodies. HHV-8
      reactivity was more common among HIV-infected women; 12 (4.0%; 95% confidence
      interval [CI], 2.1%-6.9%) of the 302 HIV-infected participants vs 1 (1.2%; 95%
      CI, 0.03%-6.4%) of the 84 HIV-uninfected participants were seropositive for HHV
      8, though the difference did not attain statistical significance (odds
      ratio=3.43; 95% CI, 0.49-148.6). Two of the HIV-infected women had Kaposi sarcoma
      lesions and both were seropositive. CONCLUSIONS: The prevalence of HHV-8
      seropositivity among the group of HIV-infected women was dramatically lower than
      that recently reported among HIV-infected homosexual and bisexual men (30%-35%).
      This finding parallels the lower prevalence of Kaposi sarcoma among women in
      contrast to men with HIV infection. These data further extend the correlation of
      HHV-8 serological reactivity with risk of Kaposi sarcoma and are consistent with
      an important role for HHV-8 infection in development of Kaposi sarcoma.

PMID- 9020273
TI  - Treatment of severe systemic inflammatory response syndrome and sepsis with a
      novel bradykinin antagonist, deltibant (CP-0127). Results of a randomized, double
      blind, placebo-controlled trial. CP-0127 SIRS and Sepsis Study Group.
AB  - OBJECTIVE: To test the effect of a novel bradykinin antagonist, deltibant (CP
      0127), on survival, organ dysfunction, and other outcomes in patients with the
      systemic inflammatory response syndrome (SIRS) and presumed sepsis. DESIGN:
      Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging
      trial. Follow-up for 28 days or until death. SETTING: A total of 47 US referral
      hospitals. PATIENTS: A total of 504 patients with SIRS and documented evidence of
      infection plus either hypotension or dysfunction of 2 organ systems.
      INTERVENTIONS: Three-day continuous intravenous infusion of either placebo or 1
      of 3 doses (0.3, 1.0, or 3.0 microg x kg(-1) x min(-1)) of deltibant. Concurrent
      therapy at the discretion of the treating physician. MAIN OUTCOME MEASURE: Risk
      adjusted, 28-day, log-normal intent-to-treat survival analysis. Risk adjustment
      was performed using a study-specific risk model derived from the APACHE III
      database. RESULTS: Deltibant had no significant effect on risk-adjusted 28-day
      survival. In a posthoc analysis, risk-adjusted 7-day survival showed a
      nonsignificant trend toward improvement (P=.09). The 28-day risk-adjusted
      survival in the prospectively defined subset of patients with gram-negative
      infections showed a statistically significant improvement (P=.005). CONCLUSIONS:
      Deltibant may have some effect on survival in patients with SIRS and gram
      negative sepsis; however, additional studies would be required to prove this.

PMID- 9020274
TI  - Clinical prediction rules. A review and suggested modifications of methodological
      standards.
AB  - BACKGROUND: Clinical prediction rules are decision-making tools for clinicians,
      containing variables from the history, physical examination, or simple diagnostic
      tests. OBJECTIVE: To review the quality of recently published clinical prediction
      rules and to suggest methodological standards for their development and
      evaluation. DATA SOURCES: Four general medical journals were manually searched
      for clinical prediction rules published from 1991 through 1994. STUDY SELECTION:
      Four hundred sixty potentially eligible reports were identified, of which 30 were
      clinical prediction rules eligible for study. Most methodological standards could
      only be evaluated in 29 studies. DATA ABSTRACTION: Two investigators
      independently evaluated the quality of each report using a standard data sheet.
      Disagreements were resolved by consensus. DATA SYNTHESIS: The mathematical
      technique was used to develop the rule, and the results of the rule were
      described in 100% (29/29) of the reports. All the rules but 1 (97% [28/29]) were
      felt to be clinically sensible. The outcomes and predictive variables were
      clearly defined in 83% (24/29) and 59% (17/29) of the reports, respectively.
      Blind assessment of outcomes and predictive variables occurred in 41% (12/29) and
      79% (23/29) of the reports, respectively, and the rules were prospectively
      validated in 79% (11/14). Reproducibility of predictive variables was assessed in
      only 3% (1/29) of the reports, and the effect of the rule on clinical use was
      prospectively measured in only 3% (1/30). Forty-one percent (12/29) of the rules
      were felt to be easy to use. CONCLUSIONS: Although clinical prediction rules
      comply with some methodological criteria, for other criteria, better compliance
      is needed.

PMID- 9020275
TI  - Periprocedural cardiac marker elevation after percutaneous coronary artery
      revascularization. Importance and implications.

PMID- 9020276
TI  - The Swedish prostate cancer paradox.

PMID- 9020277
TI  - Navigating to knowledge. Tools for finding information on the Internet.

PMID- 9020278
TI  - Radiotherapy with concomitant continuous cisplatin infusion for unresectable
      tumors of the upper aerodigestive tract: results of a phase I study.
AB  - A phase I-II study was initiated in February 1991 of concomitant radiation and
      cisplatin (CDDP) in the treatment of unresectable head and neck squamous cell
      carcinomas (n = 12). The first patient was treated palliatively for a cervical
      recurrence of laryngeal cancer. The 11 other patients had locally advanced (stage
      IV) previously untreated carcinomas of the oropharynx (n = 9), hypopharynx (n =
      1), or cervical node with unknown primary site (n = 1). Standard external
      radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron
      beam) for the first patient and 72 Gy/8 weeks (Co60 beam) for the other 11
      patients. CDDP was infused continuously during the entire radiation treatment, 5
      days/week. The starting dose was 4 mg/m2/day and was escalated by increments of 1
      mg/m2/day; dose-limiting toxicity was observed at 7 mg/m2/day. Neutropenia (grade
      4, one patient; grade 3, three patients) and thrombocytopenia (grade 3, one
      patient; grade 2, one patient) were the limiting factors. Therefore, the
      recommended dose of CDDP is 6 mg/m2/day. All patients but one completed the
      scheduled radiation. For the entire group, mucositis was not more severe than
      that observed with radiotherapy alone. There was no nephro-, oto-, or
      neurotoxicity. A complete response was obtained in eight (66%) patients. Of
      these, four were free of disease 12-34 months after completion of treatment and
      one had a total glossectomy for a tongue necrosis. For the whole series, the mean
      overall survival was 16 months posttreatment. Pharmacokinetic analysis indicated
      the total cisplatin accumulation at the end of treatment to be 743-1551 ng/ml.
      Accumulation of ultrafilterable platin was noted in only one patient (137 ng/ml
      at the end of treatment).

PMID- 9020279
TI  - Pilot study of concurrent chemotherapy and radiotherapy for stage IV
      nasopharyngeal cancer.
AB  - Nasopharyngeal carcinoma (NPC) is a more radio- and chemosensitive tumor than all
      other head and neck cancers. Between September 1991 and December 1992, a total of
      19 patients (13 men and six women; median age, 44 years) with AJCC stage IV NPC
      were entered into a pilot study of concurrent chemoradiotherapy. Pathology showed
      either poorly differentiated epidermoid carcinoma or undifferentiated carcinoma.
      Radiotherapy was delivered using a telecobalt unit and 10-MV x-rays and by
      conventional fractionation (1.8-2.0 Gy/fraction, 5 fractions/week). The total
      doses delivered were 70-75 Gy to the primary tumor and neck positive region, and
      50-55 Gy to the neck negative area. Chemotherapy with cisplatin (10 mg/m2/day,
      days 1-5) and 5-fluorouracil (500 mg/m2/day, continuously infused for 5 days) was
      administered concurrently during weeks 1 and 5 of radiotherapy. The major
      toxicities were mucositis (42% had grade III and 58% grade II) and leukopenia
      (nadir white blood cells <3,000/mm3 in eight of 19). Although four patients
      required a delay in their second cycle of concurrent chemotherapy or had their
      radiotherapy interrupted for 1 week, all 19 patients completed the planned
      treatment and achieved a 100% complete response rate. After a median follow-up
      period of 42 months, one patient suffered from neck recurrence plus distant
      metastasis, and three patients developed distant metastases alone. The 3-year
      overall and disease-free survival rates are 89.5% and 83.3%, respectively. Our
      data indicated that concurrent chemoradiotherapy for advanced NPC is both
      feasible and effective, with acceptable toxicities. A phase III randomized trial
      to compare the efficacy of concurrent chemoradiotherapy and radiotherapy alone
      deserves to be studied further.

PMID- 9020280
TI  - Integration of surgery in multimodality therapy for esophageal cancer.
AB  - BACKGROUND: While adding chemotherapy to radiation for the treatment of
      esophageal cancers has been shown to be beneficial, surgery usually follows
      treatment or is omitted. In either case, regional control remains problematic.
      The purpose of this study was to test the feasibility of using chemotherapy and
      radiation following surgery in the treatment of of esophageal cancer and to
      assess the impact of this approach on regional control and survival. PATIENTS AND
      METHODS: Twenty-five patients with esophageal cancer were treated in a phase I
      pilot protocol consisting of initial esophagectomy with gastroesophagostomy and
      subsequent combined chemotherapy and radiation. Chemotherapy consisted of
      cisplatin given on day 1 and 5-fluorouracil (FU) on days 1-5 by continuous
      infusion. Radiation therapy was administered in varying fractionation schedules
      of once or twice daily concomitantly with the chemotherapy. Treatment was
      repeated every other week for two to four cycles. Median follow-up was 42 months.
      RESULTS: Acute toxicities (mucositis and cytopenias) were common but not worse
      than grade 3. Higher doses of 50 Gy with 2 Gy b.i.d. hyperfractionation caused
      late complications in four of 10 patients, (two lethal). Control of local disease
      for all patients was excellent with only two known and two possible local
      recurrences (16%) but distant metastases were common (46%). Disease-free survival
      was 58 and 30% at 1 and 2 years, respectively. Survival was 58 and 32% at 1 and 2
      years, respectively (median survival, 19 months). CONCLUSION: The local control
      rate and survival were better than those in our historical experience with
      cisplatin and 5-FU chemotherapy and radiation given prior to surgery. A dose
      fractionation schedule of < 2 Gy up to a total of 50 Gy b.i.d. is recommended to
      avoid late adverse effects. The role of surgery will be defined by randomized
      studies. Better systemic therapy is needed to impact on systemic failure.

PMID- 9020282
TI  - Isolated facial nerve palsy from metastasis to the temporal bone: report of two
      cases and a review of the literature.
AB  - Isolated facial nerve paralysis is rarely the result of metastasis. We describe
      two cases (the fourth and fifth cases ever documented) with facial nerve palsy
      secondary to metastatic adenocarcinoma to the temporal bone. We also review the
      pathogenesis and presentation of facial nerve paralysis from metastasis and
      discuss a possible treatment strategy.

PMID- 9020281
TI  - Treatment of squamous cell carcinoma of the esophagus with alternating
      radiotherapy and chemotherapy (cisplatin, methotrexate, and peplomycin).
AB  - Between 1985 and 1990, 20 patients with stage 2 and 3 esophageal cancer without
      esophagopulmonary fistulas were treated with alternating radiotherapy and
      chemotherapy (cisplatin, methotrexate, and peplomycin). Patients given the
      combined therapy received courses of chemotherapy during weeks 1 and 6 and
      radiotherapy during weeks 2-5 and 7-9. Chemotherapy consisted of i.v. cisplatin
      (80 mg/ m2 of body surface area) on day 1, i.v. methotrexate (40 mg/ m2) on day
      2, and s.c. peplomycin (10 mg/day) continuously from day 2 to day 5. Radiotherapy
      was external irradiation with or without intracavitary irradiation. In seven
      cases, external irradiation alone was administered at 65-70 Gy, and in 13 cases,
      external irradiation (50-55 Gy) was combined with intracavitary irradiation (14
      20 Gy). At the end of treatment, the rate of complete response was 60% with an
      overall response rate of 95%. Five-year total survival was 25%; cause-specific
      survival was 36.8%. The most common acute toxicities were bone marrow
      suppression, hepatic and renal damage, pneumonitis, and esophagitis. There was no
      life-threatening toxicity.

PMID- 9020283
TI  - Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung
      cancer: a Cancer and Leukemia Group B study (CALGB 8832).
AB  - The maximum tolerated dose (MTD) of etoposide and carboplatin without growth
      factor support was previously defined by Cancer and Leukemia Group B (CALGB) as
      200 and 125 mg/m2/day x 3, respectively, given every 28 days to previously
      untreated patients who have extensive, small-cell lung cancer (SCLC).
      Myelosuppression was dose-limiting. The purpose of this phase I trial was to
      determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support
      allows the dosage of the combination of etoposide and carboplatin to be increased
      above the previously determined MTD. In this CALGB study of 44 evaluable patients
      with performance status 0-2, cohorts were treated with etoposide and carboplatin
      given intravenously on days 1-3 followed by GM-CSF (molgramostim) given
      subcutaneously on days 4-18. Four dose levels of bacteria-derived recombinant GM
      CSF (5, 10, 20 microg/kg/day and 5 microg/kg every 12 h), three dose levels of
      etoposide (200, 250, and 300 mg/m2/day x 3), and two dose levels of carboplatin
      (125 and 150 mg/m2/day x 3) were evaluated. There was no chemotherapy dose
      escalation in individual patients. With 5 microg/kg/d GM-CSF, the first etoposide
      and carboplatin cycle of 300 and 150 mg/m2/day x 3, respectively, could be
      administered with acceptable toxicity. However, GM-CSF did not allow repeated
      administration of this dose-escalated regimen every 21 days, since delayed
      platelet and/or neutrophil recovery was dose limiting in later cycles. These
      results demonstrate that GM-CSF alone has limited capability to support the
      repeated administration of high doses of etoposide and carboplatin. CALGB
      currently is testing the ability of interleukin (IL)-6 given with GM-CSF to
      ameliorate the cumulative myelosuppression of this intense regimen.

PMID- 9020284
TI  - Combined carboplatin and cisplatin therapy in patients with advanced non-small
      cell lung cancer.
AB  - Combining cisplatin and carboplatin may eliminate some of the toxic effects of
      each agent and permit the use of higher doses, because these agents have
      different pharmacodynamics and dose-limiting toxicities. We investigated the
      safety and efficacy of these agents in combination. The toxicity profile was
      evaluated in a Phase I trial in 18 patients with advanced non-small cell lung
      cancer (NSCLC). Carboplatin was administered in doses ranging from 200 to 400
      mg/m2 on day 1 and cisplatin at a dose of 80 mg/m2 on day 3. Only one cycle of
      chemotherapy was administered. Thrombocytopenia was the dose-limiting toxic
      effect. The maximal tolerated dose of carboplatin was 350 mg/m2. We then
      investigated the efficacy of the optimal dose of this combined chemotherapy in a
      Phase II trial in 13 patients. We used a carboplatin dose of 300 mg/m2 for safety
      in the Phase II trial. Three of 13 patients developed grade 3-4 hematologic
      toxicity, which was improved without major complications. A partial response was
      observed in 5 of 13 patients (38.5%). Combination chemotherapy with carboplatin
      (day 1, 300 mg/m2) and cisplatin (day 3, 80 mg/m2) showed promising effects in
      patients with advanced NSCLC.

PMID- 9020285
TI  - Phase II chemoprevention trial of oral fenretinide in patients at risk for
      adenocarcinoma of the prostate.
AB  - Prostate cancer is the most common cancer diagnosed in American men. The need to
      find effective means of preventing this disease is clear. Vitamin A and its
      analogues (retinoids) act as transcriptional regulators within the nucleus and
      have been tested as both preventative and therapeutic agents in human malignancy.
      Fenretinide (N-4-hydroxyphenyl retinamide) (4HPR) has been found to be relatively
      nontoxic in preclinical experiments and early clinical trials. Its toxicity and
      feasibility for use as a chemoprevention agent in men at high risk for prostate
      cancer was evaluated in this study. Twenty-two patients were entered into a
      clinical trial that involved taking 4HPR for twelve 28-day cycles. Eight patients
      with negative prestudy biopsies had positive prostate biopsies prior to or at the
      time of their 12th cycle evaluation. This led to early closure of the study. 4HPR
      was well-tolerated, and no major toxicities were associated with its use. The
      significance of this study is limited due to small sample size. Chemoprevention
      studies such as this can be difficult to complete because of the commitment
      required of otherwise healthy individuals; nevertheless additional dosages and
      schedules for 4HPR administration merit further investigation.

PMID- 9020286
TI  - Treatment of metastatic carcinoma of the prostate.
AB  - Disseminated carcinoma of the prostate (CaP) is a common manifestation of this
      disease. Metastatic CaP in the United States is seen in about 45,000 patients
      each year at diagnosis. At least the same number of patients who have had prior
      definitive treatment with surgery or radiotherapy develop evidence of metastatic
      disease. Hormonal management is the most important and well established treatment
      for patients with prostatic metastases. Orchiectomy remains the most efficient
      and most cost effective therapy in a rapid ablation of testicular androgens. Due
      to a well known psychological reaction to castration which is seen in many
      patients, diethylstilbestrol (DES) is a good alternative and cost effective
      therapy. The mode of action of DES is to suppress LH production and to slowly,
      indirectly, decrease serum testosterone level. In recent years, total androgen
      blockade (TAB) has become a widely accepted treatment option. This treatment has
      been shown in several clinical trials to be effective and well tolerated by the
      patients. A major problem with a routine use of TAB is a relatively high cost of
      this therapy. In a European prospective randomized trial, goserelin acetate
      flutamide combination significantly increased time to progression when compared
      with orchiectomy alone. Patients with localized and symptomatic metastases are
      best treated with radiotherapy. Those with multiple sites of involvement are best
      treated with strontium-89 which results in a good palliation in a majority of
      patients. Nearly all hormonally treated patients, with metastatic CaP, eventually
      show tumor progression. Presently available chemotherapy is of a low
      effectiveness and should not be used for these patients outside of controlled
      clinical trials. Current research is directed to identify effective therapy for
      hormone refractory patients. Immunotherapy and gene therapy may be useful future
      therapeutic options.

PMID- 9020287
TI  - Radiation therapy for intrathoracic recurrence of non-small cell lung cancer.
AB  - Fifty-two of 2,315 patients (2.4%) with non-small cell lung cancer (NSLC) treated
      with radiation therapy at the Mallinckrodt Institute of Radiology and St. Luke's
      Hospital between 1975 and 1988 presented with local recurrence after definitive
      surgery. No patient received radiation therapy after surgery as part of initial
      treatment and none had evidence of distant metastases at the time of local
      recurrence. The median time to first recurrence was 14 months. At recurrence,
      patients presented with disease in the bronchial stump (eight patients),
      ipsilateral lung parenchyma (10), chest wall (six), regional lymph nodes (five),
      or some combination thereof (23). Sixty-five percent of patients had histologic
      evidence of recurrence. Radiation therapy consisted of > 5,000 cGy in
      conventional fractionation to areas of gross disease in 35 of 52 patients. Of 15
      patients receiving > 6,000 cGy, 13 had a favorable--complete (CR) or partial (PR)
      response--tumor response to radiation therapy. Among these patients, local
      control was achieved in 70% of patients with marginal recurrences (i.e., stump,
      parenchyma, or chest wall) and in 50% with nodal recurrences. The median survival
      after radiation therapy for all patients was 8.5 months. The best indicators for
      long-term survival were the interval from initial surgery to first recurrence and
      tumor response to radiation therapy.

PMID- 9020288
TI  - A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in
      advanced non-small-cell lung cancer.
AB  - It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA)
      is synergistic in vitro. The objective of this study was to evaluate the
      therapeutic effect and safety of the two platinum compounds in combination with
      etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients
      were registered. Based on the results of a phase I study, patients were treated
      with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and
      etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10
      women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell
      carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n
      = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40;
      95% confidence interval (CI) 18-47%] was achieved. The response rates in patients
      with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median
      duration of response was 47.1 weeks and the overall median survival time was 57.1
      weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV-
      occurred in nine and 11 patients, respectively. Nonhematological toxicities were
      mainly nausea, vomiting, and alopecia. In conclusion, further investigations of
      this regimen are warranted in the treatment of NSLC.

PMID- 9020289
TI  - Radiation therapy for squamous cell carcinoma in dystrophic epidermolysis
      bullosa: case reports and literature review.
AB  - Dystrophic epidermolysis bullosa (DEB) is a debilitating systemic disease
      frequently associated with biologically aggressive secondary squamous cell
      carcinomas arising from affected skin or mucosal surfaces. Treatment of these
      carcinomas with surgery, chemotherapy, or radiation is complicated by inherently
      poor wound healing. We report on two DEB patients treated with radiation therapy
      for locally advanced squamous cell carcinoma, and retrospectively analyze 10 DEB
      patients treated with radiation, reported in the literature. Of the 11 fully
      available and described case results from radiation therapy, six (54%) patients
      demonstrated a partial tumor response. All patients receiving > 4,500 cGy
      developed moist skin desquamation and delayed skin healing. Radiation therapy may
      be of benefit in palliating DEB patients who have locally advanced carcinoma, but
      has been associated with enhanced normal tissue toxicity, suggesting a narrow or
      absent therapeutic index between irradiated carcinoma and skin.

PMID- 9020290
TI  - Primary testicular non-Hodgkin's lymphoma: a clinical study and review of the
      literature.
AB  - Non-Hodgkin's lymphoma (NHL) of the testis is a rare disease, and treatment
      outcome is generally poor. In this retrospective study, we investigated treatment
      results for testicular NHL in an attempt to develop an effective treatment policy
      for this disease. The survival rate and characteristics were retrospectively
      analyzed in eight patients with NHL of the testis who were treated between 1969
      and 1991 at Kyoto University Hospital, Department of Radiology. Four patients
      were at stage IEA, one at stage IIEA, and three at stage IVEA. Of the eight
      testicular lymphomas, six were classed as intermediate grade lymphomas and two as
      high-grade lymphomas according to the Working Formulation. All of the eight
      patients received orchiectomy. Six patients received combined chemotherapy and
      radiation therapy as the primary treatment for the disease. One patient each was
      treated with radiation therapy alone or combination chemotherapy alone. The 5
      year overall and disease-free survival rate was 45 and 33%, respectively. Even
      though almost all of the patients had received combination chemotherapy, high
      incidence of relapse in the central nervous system (CNS) was observed.
      Prophylactic treatment against such recurrence may be necessary to improve the
      treatment outcome of patients with testicular NHL.

PMID- 9020291
TI  - Infusional chemotherapy combined with recombinant human granulocyte colony
      stimulating factor: advantages and limitations.
AB  - We have studied the simultaneous administration of granulocyte colony stimulating
      factor (G-CSF), given concomitantly with an infusion of either doxorubicin or
      ifosphamide--the former, both intraarterially (i.a.) and intravenously (i.v.),
      the latter, intravenously--to a group of patients with various malignancies. Such
      simultaneous administration enabled us to substantially increase the dosage
      intensity of both, thereby increasing the effectiveness of each drug. No untoward
      effects have been noted to date.

PMID- 9020292
TI  - Evaluation of intravenous 6-thioguanine as first-line chemotherapy in women with
      metastatic breast cancer.
AB  - 6-Thioguanine (6-TG) is a purine analog that has marked variability in plasma
      concentration after oral administration. Following the development of a multiple
      day i.v. regimen, we performed a phase II trial of this agent as first-line
      chemotherapy in women with metastatic breast cancer. Forty-one patients with
      measurable (31 patients) or evaluable (10 patients) disease were entered into
      this trial. 6-TG was administered i.v. over a 10 min period daily for 5
      consecutive days, with a planned cycle length of 35 days. The daily dosage level
      was 55 mg/m2 in the first 15 patients, but this was increased to 65 mg/m2 in the
      remaining patients due to inadequate myelosuppression at the lower dose. Six
      patients, all with measurable disease, achieved a complete response (CR) (two
      patients) or a partial response (PR) (four patients). Three responses occurred at
      the 55 mg/m2 level and three at the 65 mg/m2 level. The 95% confidence interval
      (CI) for the true response rate among patients with measurable disease was 6-39%.
      The median time to progression was 140 days and median survival time was 460
      days. The regimen was well tolerated. We conclude that 6-TG, as given in this
      study, has limited activity as first-line chemotherapy for women with metastatic
      breast cancer.

PMID- 9020293
TI  - Aortic wall sarcoma with tumor emboli and peripheral ischemia: case report with
      review of literature.
AB  - Primary malignant tumors of the aorta are rare, only a handful of isolated cases
      having been described in the literature. Preoperative diagnosis of these tumors
      is more the exception than the rule. Diagnosis of aortic tumors is difficult as
      they can mimic many diverse conditions including atherosclerosis. We report a
      patient who presented with lower extremity claudication, renal infarction, and
      diffuse atherosclerosis and who was found to have tumor fragments in blood clots
      but no evidence of a primary tumor. Immunohistochemistry narrowed the
      differential diagnosis to a type of sarcoma. Six months later, he developed right
      flank pain due to a malignant fibrous histiocytoma that involved the abdominal
      aorta and that had initially manifested as tumor emboli.

PMID- 9020294
TI  - A phase II trial of edatrexate in previously treated squamous cell cervical
      cancer: a Gynecologic Oncology Group study.
AB  - A Phase II trial of edatrexate in patients with recurrent cervical carcinoma was
      conducted by the Gynecologic Oncology Group (GOG). Twenty patients were treated
      with edatrexate at a dose of 80 mg/m2 i.v. weekly for 5 consecutive weeks per
      cycle. Four patients received an inadequate trial and were inevaluable for
      response. Among the 16 patients evaluable for response, there were no objective
      responses: 50% had stable disease, 50% had progressive disease. All 20 patients
      were evaluable for toxicity, predominantly stomatitis and bone marrow suppression
      were substantial. Grades 3-4 bone marrow toxicity were observed in eight of 20
      (40%) patients, and there were two deaths due to neutropenic sepsis. Fanconi's
      syndrome, possibly treatment related, was seen in two patients. Edatrexate
      administered in this dose and schedule has no demonstrated activity and has
      severe toxicity in patients with previously-treated advanced cervical cancer.

PMID- 9020295
TI  - Treatment of advanced pancreatic adenocarcinoma with 5-FU, leucovorin, interferon
      alpha-2b, and cisplatin.
AB  - Previous laboratory and clinical studies support the ability of interferon (IFN)
      to enhance the antitumor properties of chemotherapy agents, including cisplatin
      and 5-fluorouracil (5-FU). A phase I-II clinical trial was initiated to treat
      several tumor types with IFN-alpha-2b, cisplatin, 5-FU, and leucovorin (LV),
      given daily for 5 days of a 28-day cycle. Because of preliminary results, this
      was continued as a phase II trial in 18 patients with metastatic adenocarcinoma
      of the pancreas. Each treatment day consisted of IFN 5 million u/m2 s.c.
      (maximum, 10 million U), CDDP 20 mg/m2 i.v. over 1 h, LV 20 mg/m2 i.v.p., and 5
      FU 250-275 mg/m2 i.v.p. All patients had measurable disease with no prior
      chemotherapy for metastatic disease, and all had an Eastern Cooperative Oncology
      Group (ECOG) performance status of 1. Six of the 16 patients evaluable for
      response had partial responses (PRs) (37.5%) with a median response duration of 4
      months, and all responding patients survived > or = 8 months. Median survival of
      all 18 treated patients was 5 months. Severe gastrointestinal toxicity (nausea,
      diarrhea, or requirement for i.v. hydration) was common. Grade 4 hematologic
      toxicity was seen in six patients. The response rate observed is promising and
      supports the concept that IFN may potentiate the effects of standard chemotherapy
      agents. However, the toxicities observed with this dosage schedule were
      considerable and further studies are needed to develop a less toxic regimen.

PMID- 9020296
TI  - Phase II trial of piroxantrone in advanced squamous cell carcinoma of the cervix:
      a Gynecological Oncology Group study.
AB  - Piroxantrone was administered at a starting dose of 160 mg m2 given as a 1-h
      infusion every 3 weeks to 19 patients with histologically confirmed advanced,
      persistent, or recurrent squamous cell carcinoma of the cervix. All patients were
      required to have measurable disease and no prior chemotherapy. Eighteen women
      were evaluable for toxicity and response. Toxicity was modest and consisted
      primarily of myelosuppression with six (33%) patients experiencing grade 3 or 4
      leukopenia. There were no complete (CR) or partial responses (PR) among the 18
      evaluable patients. Six (33%) patients had stable disease while on treatment and
      12 (67%) patients experienced progressive disease. Piroxantrone appears to have
      no beneficial effect in advanced or recurrent squamous cell cancer of the cervix
      at this dose and schedule.

PMID- 9020297
TI  - Tumor lysis syndrome in invasive thymoma with peripheral blood T-cell
      lymphocytosis.
AB  - Tumor lysis syndrome has rarely been observed in solid tumors. We report a case
      of a patient with advanced invasive thymoma associated with peripheral blood T
      cell lymphocytosis in whom tumor lysis syndrome developed after chemotherapy. The
      potential for tumor lysis syndrome should be anticipated when treating extensive
      thymoma.

PMID- 9020298
TI  - CODBLAM IV chemotherapy for large cell lymphoma: sequential use of infusional
      vincristine and bleomycin and "high dose" consolidation.
AB  - BACKGROUND: Based on prior results in large cell lymphoma (LCL) with COPBLAM
      (Cyclophosphamide, Oncovin, Prednisone, Bleomycin, Adriamycin, Matulane) I and
      COPBLAM III, CODBLAM (Cyclophosphamide, Oncovin, Dexamethasone, Bleomycin,
      Adriamycin, Matulane) IV was developed to intensify treatment further by
      utilizing four sequential cycles of infusional chemotherapy followed by high-dose
      chemotherapy and cycle active agents. METHODS: Sixty-one patients with LCL,
      mostly B-cell lymphoma, with 54% >60 years of age, were treated with daily
      continuous infusion of vincristine 1.0 mg/m2 days 1-2, bleomycin 4 mg/m2 i.v.
      push x 1 only followed by daily infusion 4 mg/m2 days 1-5, dexamethasone 10 mg/m2
      days 1-5, procarbazine 100 mg/m2 orally days 1-5, doxorubicin 35 mg/m2 i.v. push
      day 1 (escalated), and cyclophosphamide 350 mg/m2 i.v. push day 1 (escalated),
      all given every 3 weeks for four cycles. After infusions, patients were restaged
      and treated with single courses of doxorubicin 90 mg/ m2 i.v. push followed at 3
      weeks with cyclophosphamide 1500 mg/m2 i.v. push (both with concomitant
      vincristine 1 mg/m2 i.v. push and dexamethasone 10 mg/m2 p.o. daily for 5 days).
      Remaining treatment consisted of methotrexate 120 mg/m2 i.v. push with citrovorum
      rescue, cytarabine 250 mg/m2 i.v. push, and etoposide 100 mg/m2 i.v. infusion
      over 1 h, all given every 10 days for six cycles. RESULTS: The overall complete
      response (CR) rate was 88%. Of all patients, 36 (59%) are sustained disease free
      at a median follow-up time of 55 months. In patients age < or = 60 years, 89%
      achieved CR and 85% of patients age >60 years attained CR. CR was achieved in 83%
      of patients with constitutional B-type symptoms, 69% of patients with bulky
      adenopathy, and 86% of patients with immunoblastic histology. Toxicity was
      primarily pulmonary, occuring in 15% of patients. One toxic death was observed.
      CONCLUSIONS: Infusional CODBLAM IV may represent an effective and unique
      treatment for LCL.

PMID- 9020299
TI  - Preoperative simultaneous chemoradiotherapy in locally advanced cancer of the
      oral cavity and oropharynx.
AB  - Combined chemoradiotherapy (CT/RT) treatments appear to yield better results for
      advanced tumours of the head and neck than do conventional therapies. In the
      present study, CT/RT was used preoperatively in unresectable tumors of the oral
      cavity and oropharynx. Forty patients were entered prospectively into a phase II
      study. Treatment consisted of three cycles of chemotherapy with cisplatin and 5
      day infusion of fluorouracil (FU), and the addition of simultaneous radiotherapy
      (30 Gy) from the second to third cycles. Patients with resectable residual
      disease or complete clinical response underwent surgery. All patients later
      received a second phase of irradiation (30 Gy) and two cycles of chemotherapy
      only in responders. During the first phase of treatment, 22 (55%) patients
      presented mucositis grades III-IV. Mean weight loss was 7%. Twelve patients were
      admitted for parenteral nutrition. Thirty-six (90%) patients obtained clinical
      response, which was complete in 15 (37%). Thirty-two of the 40 underwent surgery.
      The percentage of pathologic complete responses (PCR) was 35% (14 patients). With
      a median follow-up of 21 months, the median survival of patients was 23 months,
      and 19 (47%) of them are disease-free. A high PCR rate was attained with this
      treatment regimen. Toxicity was significant, but tolerable with adequate support
      measures.

PMID- 9020300
TI  - Functioning pancreatic acinar cell carcinoma: immunohistochemical and
      ultrastructural analyses.
AB  - Acinar cell carcinoma (ACC) of the pancreas is a rare malignancy accounting for <
      1% of pancreatic neoplasms. We report the clinical and biological characteristics
      of this carcinoma from two cases that were of interest because of their similar
      presentation: extensive subcutaneous fat necroses from excessive lipase
      production by these tumors. Immunohistochemical and ultrastructural analyses of
      both tumors were consistent with an acinar cell line origin. Recognition of the
      association between subcutaneous panniculitis and pancreatic neoplasm may prevent
      long delays in the diagnosis and treatment of this malignancy.

PMID- 9020301
TI  - Assessment of the genotoxic risk from laxative senna products.
AB  - Laxative senna products and several of their specific components have been
      submitted to a large number of genetic tests. While most studies gave negative
      responses, results from some of the studies suggest that components of senna
      products, particularly emodin and aloe-emodin, have genotoxic activity.
      Assessment of the genotoxicity profile of these substances, in light of other
      data from animal and human metabolism or kinetic studies, human clinical trials
      and rodent carcinogenicity studies do not support concerns that senna laxatives
      pose a genotoxic risk to humans when consumed under prescribed use conditions.

PMID- 9020302
TI  - Overview of ovarian follicular development: considerations for the toxicologist.
AB  - Folliculogenesis is the lengthy process that results in the production of a
      species-specific, highly consistent number of follicles, which ripen during each
      reproductive cycle at precisely the appropriate time for ovulation. Certain
      features of folliculogenesis may have special implications for toxicologists
      studying effects of environmental mutagens on oocytes. Such features include the
      constantly changing geometry of the ovarian follicle, the great excess of
      developing follicles (most of which will degenerate rather than ovulate), the
      exponential nature of follicular growth, the acceleration of cell proliferation
      as follicular size increases, and the location of the principal feedback
      regulatory step at the penultimate stage of the developmental process. Because
      the ovary can respond quickly and completely to loss of homeostasis over the
      short term, damage from toxic insult may not be readily apparent. However, long
      range fertility may nevertheless be impaired. The finite size of the follicular
      pool and the absence of feedback regulatory steps during the early stages of
      follicular growth render the ovary incapable of restoring the status quo among
      small and medium-sized follicles. This will eventually result in loss of fine
      control over the number of follicles that ripen and the regularity of the
      reproductive cycles and could reduce the overall duration of the fertile life
      span.

PMID- 9020303
TI  - Effects of the DNA topoisomerase II inhibitor merbarone in male mouse meiotic
      divisions in vivo: cell cycle arrest and induction of aneuploidy.
AB  - In order to clarify possible risks of aneuploidy induction in germ cells by
      cancer chemotherapy we studied effects of a non complex-stabilizing DNA
      topoisomerase II (topo II) inhibitor merbarone in male mouse meiotic divisions in
      vivo. Two cytogenetic approaches were used: (1) C-banding on meiotic chromosome
      preparations and (2) analysis of spermatid micronuclei (MN) combined with
      immunocytochemical staining of kinetochore proteins using CREST serum. For
      comparison, another topo II inhibitor, VP-16, known to form cleavable complexes,
      was studied. The microdissection technique of mouse seminiferous tubules enabled
      us to carefully examine effects at specific phases of meiosis. Merbarone
      injections increased percentages of polyploid and hypoploid metaphase II
      spermatocytes at time intervals corresponding to the treatment of the first
      meiotic division and diplotene-diakinesis. The highest level of MN induction (5.8
      MN/1000 spermatids, P < 0.001) was observed in animals injected 48 hours before
      the harvest, corresponding to the treatment of diplotene-diakinesis
      spermatocytes. Most of the induced MN (80%) contained kinetochore signals,
      indicating that they resulted from detachment of a whole bivalent or chromosome
      from the meiotic spindle. The high frequency of MN with two kinetochore signals
      at opposite sides (33%) most likely denotes lagging of whole bivalents during MI.
      Inhibition of cell proliferation was determined by scoring cells arrested at
      different phases of MI and MII. All groups of treated animals showed a clear
      increase in the frequency of arrested divisions compared to controls (P < 0.001).
      Thus, merbarone was shown to severely damage normal meiotic processes.

PMID- 9020304
TI  - Quantification of hprt gene deletions mediated by illegitimate V(D)J
      recombination in peripheral blood cells of humans.
AB  - V(D)J recombinase is normally involved in the highly regulated rearrangement of
      immunoglobulin and T-cell-receptor gene segments (in B and T cells, respectively)
      to form functional antibody genes and T-cell-receptor genes. Occasionally, this
      tightly controlled process acts on inappropriate places in the genome and results
      in deletions and translocations. Some of these illegitimate V(D)J recombinase
      mediated events have been implicated in the genetic changes associated with
      several forms of leukemia and lymphoid malignancy. We have developed a sensitive,
      specific polymerase chain reaction (PCR)-based assay to quantify such events in
      the peripheral blood cells of humans. This assay detects a V(D)J recombinase
      mediated deletion in the hprt gene, which codes for a housekeeping enzyme and is
      not implicated in cancer development. Alterations in this gene serve as a
      surrogate indicator for these illegitimate events, which may be occurring
      throughout the genome. The assay involves a hemi-nested PCR with two sets of
      primers. Multiple replicates of genomic DNA (each representing 4 x 10(5) cells)
      are amplified with specific primers under conditions in which a single copy will
      give a detectable PCR product. Poisson statistics are then used to estimate the
      deletion mutant frequency. The frequency of cells with the hprt deletion among 20
      healthy young adults ranged from <1.3 x 10(-7) to 4.1 x 10(-7) and was compared
      with the frequency of t(14;18) previously determined in these same individuals.
      No correlation was found between the frequencies of these two measures of genomic
      rearrangement. The DNA sequences at the deletion junctions were determined and
      provided evidence for multiple independent mutations in some individuals. This
      assay may serve as a biomarker for the level of illegitimate V(D)J recombination
      occurring in peripheral blood cells of humans.

PMID- 9020305
TI  - Correlated mutagenesis of bcl2 and hprt loci in blood lymphocytes.
AB  - In vivo measurement of human somatic mutations may be a valuable biodosimeter of
      exposure to carcinogens and of cancer risk. We have surveyed translocations at
      the bcl2 locus in B lymphocytes, and mutations at hprt in T lymphocytes, in 120
      individuals with varying exposure to radon and cigarette smoke. bcl2 t(14:18)
      translocation is the commonest chromosomal alteration observed in non-Hodgkins
      lymphoma (NHL). We observed a significantly larger range of bcl2 translocation
      frequency (range: 0-372 x 10(-6), median: 1.9 x 10(-6)) than of hprt mutation
      frequency (range: 0-76.4 x 10(-6), median: 11.1 x 10(-6)), which is likely the
      result of clonal proliferation of deathless B cell mutants. We observed that the
      frequencies of these two distinct lymphocytic mutations are significantly
      correlated. Although some of the correlated variation is explained by age, a
      significant correlation of bcl2 mutagenesis persists after age adjustment.
      Correlated mutagenesis at distinct loci in distinct cell types could be explained
      by the existence of a mutator phenotype or by variation in exposure to
      environmental mutagens. NHL is commoner in men than in women, and our data
      indicate a trend toward higher bcl2 mutagenesis in males than females. There is
      mounting epidemiological evidence for a worldwide increase in NHL, which may have
      an environmental basis; molecular epidemiological analysis of bcl2 mutagenesis in
      exposed populations might be especially relevant to the identification of
      putative environmental causes. Given the relative ease of the bcl2 assay versus
      the hprt assay, and the consistency with which data are reproduced from
      laboratory to laboratory, it is likely that the bcl2 assay will be soon added to
      the array of assays used in human mutational surveillance.

PMID- 9020306
TI  - Micronucleus monitoring to assess human occupational exposure to organochlorides.
AB  - Health surveillance for hazardous situations due to chemical exposure, in
      particular those which are carcinogenic, requires sensitive monitoring tests.
      Although experimental studies have shown the genotoxic and carcinogenic effect of
      several organochlorides, the lack of epidemiologic studies prevents their
      classification as carcinogenic to human beings. In this context, genotoxicity
      tests of short duration in human cells gain importance. The relation between the
      clastogenic effects (chromosome breaks) and cancer induction is already known to
      the scientific literature. The micronucleus test has been proposed as a good
      indicator of clastogenesis. In the present study, we evaluated, by means of the
      micronucleus test, 41 workers of a chemical industry in the state of Sao Paulo,
      southeast region of Brazil, who had been exposed to a mixture of chlorinated
      solvents (carbon tetrachloride, perchloroethylene, and hexachlorobenzene) and 28
      workers who had not been exposed. Peripheral lymphocytes stimulated by
      phytohemagglutinin and with cytokinesis blocked by cytochalasin B were used. The
      results showed that the exposed workers presented a statistically significant
      higher frequency of micronuclei than the group which had not been exposed.

PMID- 9020307
TI  - Mutagenicity of cidial (phenthoate). I: Effect on maternal and fetal somatic
      cells.
AB  - Cidial, an organophosphorous insecticide (also known as phenthoate), was tested
      for its genotoxic effect on both maternal and fetal cells. Cidial was
      administered at three different dose levels (53.5, 106.9, and 171 mg/kg) to
      pregnant mice on day 16 of gestation. Maternal bone marrow and embryonic liver
      cells were examined for chromosomal aberrations and cellular proliferation.
      Cidial was found to increase the percentage of cells with chromosomal aberrations
      in both mothers and fetuses. It also significantly inhibited the rate of mitotic
      activity of both maternal and fetal cells, with the inhibitory effect being more
      appreciable in fetal cells than in maternal cells. The data indicate that cidial,
      which is widely used in rural areas, is hazardous to both mothers and their
      transplacentally exposed babies.

PMID- 9020308
TI  - Analysis of DNA single-strand breaks in human venous blood: a technique which
      does not require isolation of white blood cells.
AB  - For DNA strand break analysis in human white blood cells, usually metrizoate
      Ficoll centrifugation is used to isolate mononuclear cells. This procedure is
      time-consuming and requires at least 20 ml of blood per sample. Therefore, we
      developed a technique which does not require isolation of white blood cells prior
      to DNA strand break analysis by alkaline elution (direct method). The sensitivity
      of this new technique was compared to that of the standard method, which includes
      isolation of mononuclear blood cells. A statistically significant increase in
      sensitivity was observed using the direct method. After in vitro gamma
      irradiation of venous blood, an increase in the elution rate of 7.7 x 10(-3) hr(
      1)/Gy was detected if mononuclear blood cells were isolated compared to 10.5 x
      10(-3) hr(-1)/Gy with the new technique (P < 0.05). Incubation of venous blood
      with ethylene oxide for 1 hr caused an increase in the elution rate of 5.8 x 10(
      3) hr(-1)/mM ethylene oxide for the standard and 12 x 10(-3) h(-1)/mM for the
      direct method (P < 0.05). DNA single-strand breaks were detected in blood cells
      of 10 persons without any apparent genotoxic exposure. A mean normalized elution
      rate of 1.30 +/- 0.38 (95% confidence interval) was detected in isolated
      mononuclear blood cells, and a similar mean normalized elution rate of 1.41 +/-
      0.50 was obtained using the direct method. The difference was not statistically
      significant. Five patients treated with a combination chemotherapy consisting of
      cyclophosphamide (750 mg/m2 i.v.), doxorubicin (50 mg/m2 i.v.), vincristine (1.4
      mg/m2 i.v.), and prednisolone (100 mg/m2 p.o.) for non-Hodgkin's disease were
      analyzed for DNA single-strand breaks before and 16-18 hr after the application
      of chemotherapy. Increases in mean elution rate of 68% and 116% were detected
      using the standard and the direct methods, respectively. For the direct method,
      only 3 ml of venous blood were sufficient for analysis of one sample, compared to
      25 ml needed if mononuclear cells were isolated, and about 4 hr of work per assay
      can be saved.

PMID- 9020309
TI  - Role of copper and ceruloplasmin in oxidative mutagenesis induced by the
      glutathione-gamma-glutamyl transpeptidase system and by other thiols.
AB  - Glutathione is activated to a mutagen by gamma-glutamyl transpeptidase. Other
      thiols, such as cysteine, penicillamine, cysteine ethylester, and
      cysteinylglycine, are direct mutagens in the Ames Salmonella mutagenicity test.
      Thiol mutagenesis is oxidative in nature and involves H2O2 and possibly hydroxyl
      radicals. Transition metals are crucial for thiol autoxidation. The role of
      copper and ceruloplasmin (CP) in thiol-dependent mutagenesis was studied in
      Salmonella typhimurium strain TA102. Cu and CP at low concentrations enhanced
      thiol-dependent mutagenesis in the presence, but not in the absence, of added Fe.
      The degree of enhancement depended on the type of thiol. At high Cu or CP
      concentrations, thiol mutagenesis was inhibited. Cu also decreased the
      mutagenicity of H2O2. Cu- and CP-enhanced mutagenesis were inhibited by radical
      scavengers, catalase, and peroxidase but not by superoxide dismutase. The effects
      of Cu and CP on thiol-dependent mutagenesis were similar to their effects on
      thiol-driven lipid peroxidation. The results indicate that the role of Cu and CP
      in the enhancement of thiol mutagenesis is the facilitation of the transfer of
      electrons from a thiol to iron, rather than in catalysis of the Fenton reaction.

PMID- 9020310
TI  - Promotion of glutathione-gamma-glutamyl transpeptidase-dependent lipid
      peroxidation by copper and ceruloplasmin: the requirement for iron and the
      effects of antioxidants and antioxidant enzymes.
AB  - Oxidative damage (lipid peroxidation, LPO) induced in a completely defined system
      containing glutathione (GSH), purified gamma-glutamyl transpeptidase (GGT), and
      EDTA- and ADP-chelated ferric iron was enhanced by catalytic amounts of cupric
      ions and by ceruloplasmin (CP). The enhancement depended on GSH concentration,
      GGT activity, the presence of iron, and the chelation of copper by o
      phenanthroline. High concentrations of CP inhibited LPO. Cu- and CP-enhanced, GSH
      GGT-driven LPO was inhibited by the chain-breaking radical scavengers butylated
      hydroxyanisol, alpha-tocopherol, and Trolox C (a synthetic analog of alpha
      tocopherol) but not by the hydroxyl scavenger mannitol. Ascorbic acid increased
      LPO in the presence of Cu or CP. Cu-enhanced LPO was partially sensitive to
      superoxide dismutase but not to catalase or horseradish peroxidase. The results
      indicate that Cu and CP enhance thiol-driven LPO and promote thiol-dependent
      mutagenesis by a very similar, if not the same, mechanism and are in agreement
      with the idea that this enhancement is due to redox reactions of chelated Cu and
      Fe, rather than to the reactivity of Cu in the Fenton reaction.

PMID- 9020311
TI  - Plant-activation of the bicyclic aromatic amines benzidine and 4-aminobiphenyl.
AB  - Benzidine and 4-aminobiphenyl (4-ABP) are promutagenic bicyclic aromatic amines
      that are activated into frameshift and base pair substitution mutagens by plant
      systems. Using the plant cell/microbe coincubation assay, plant-activated
      benzidine from 0 to 50 microM induced a concentration-response in Salmonella
      typhimurium. At concentrations above 5 microM, plant-activated benzidine induced
      frameshift and base pair substitution mutations in the N- or O-acetyltransferase
      over-expressing strains, DJ460, YG1024, and YG1029. With plant-activated 4-ABP,
      concentrations above 250 microM induced a significant mutagenic response in
      strains YG1024 and YG1029. A tobacco cell-free mixture, TX1MX, activated
      benzidine and 4-ABP into mutagenic metabolites in S. typhimurium strains YG1024,
      YG1029, and DJ460. The mutagenic sensitivities of plant-activated benzidine and 4
      ABP were the same with two different types of plant activation systems, TX1
      suspension cells and TX1MX cell-free medium. The plant activation of these
      aromatic amines is mediated by tobacco cell peroxidase. Plant-activated benzidine
      and 4-ABP are converted into intermediates that serve as substrates for bacterial
      or humanacetylCoA: N-hydroxyarylamine N-acetyltransferase to generate the
      ultimate mutagenic products.

PMID- 9020312
TI  - Recombinagenic activity of integerrimine, a pyrrolizidine alkaloid from Senecio
      brasiliensis, in somatic cells of Drosophila melanogaster.
AB  - Integerrimine (ITR), a pyrrolizidine alkaloid from Senecio brasiliensis, was
      tested for genotoxicity using the wing somatic mutation and recombination test
      (SMART) in Drosophila melanogaster. The compound was administered by chronic
      feeding (48 hours) of 3-day-old larvae. Two different crosses involving the
      markers flare (flr) and multiple wing hairs (mwh) were used, that is, the
      standard (ST) cross and the high bioactivation (HB) cross, which has a high
      cytochrome P450-dependent bioactivation capacity. In both crosses, the wings of
      two types of progeny were analyzed, that is, inversion-free marker heterozygotes
      and balancer heterozygotes carrying multiple inversions. ITR was found to be
      equally potent in inducing spots in a dose-related manner in the marker
      heterozygotes of both crosses. This indicates that the bioactivation capacity
      present in larvae of the ST cross is sufficient to reveal the genotoxic activity
      of ITR. In the balancer heterozygotes of both crosses, where all recombinational
      events are eliminated due to the inversions, the frequencies of induced spots
      were considerably reduced which documents the recombinagenic activity of ITR.
      Linear regression analysis of the dose response relationships for both genotypes
      shows that 85% to 90% of the wing spots are due to mitotic recombination.

PMID- 9020313
TI  - Methods for improving the yield and quality of metaphase preparations for FISH
      probing of human lymphocyte chromosomes.
AB  - Procedures are described for the in vitro culture of human lymphocytes, which
      have been concentrated by density gradient centrifugation, and for a modified
      slide-making technique for the fixed cells. The method yields improved
      percentages of mitotic cells which are largely synchronized at harvest.
      Controlled placement of fixed cells on slides produces well-spread metaphase
      preparations with little background material to interfere with fluorescence in
      situ hybridization (FISH) probe procedures. The FISH reagents and microscope
      scanning time required are minimized by concentrating cells in a defined area of
      the slide.

PMID- 9020314
TI  - Rejection of spontaneously accepted rat liver allografts with
      recipientinterleukin-2 treatment or donor irradiation.
AB  - While MHC incompatible DA (RTl(a)) to Lewis (RT1(1), LEW) rat liver allografts
      are acutely rejected, the reciprocal LEW to DA liver grafts are spontaneously
      accepted. The mechanism of this acceptance remains unclear. We evaluated the
      effect of donor treatment with total body irradiation (TBI) or gadolinium
      chloride (GdCl3), and recipient treatment with exogenous IL-2 after
      transplantation on the survival of the spontaneously accepted liver grafts. Male
      LEW and DA rats were used as donors and recipients for orthotopic liver allo- or
      iso-graft transplants. The LEW liver donor was treated by TBI (10 gray) 7 days
      before transplantation, or LEW donor Kupffer cell phagocytosis was blocked with
      GdCl3 (7 mg/kg) on days -2 and -1 pretransplant. In an attempt to reverse LEW
      liver graft acceptance, 180,000 units human IL-2 (hIL-2) were administered daily
      IP to the DA liver recipients from days 1 to 7 after liver grafting. While
      untreated LEW recipients rejected DA liver grafts within 13 days, DA recipients
      accepted LEW livers indefinitely (>302 days). In contrast, irradiation of the LEW
      liver donor prevented the spontaneous acceptance by DA recipients, and resulted
      in acute rejection of the liver grafts in 9-20 days. However, spontaneous graft
      tolerance was restored by parking the irradiated LEW donor liver in naive LEW
      rats for 48 hr before retransplantation to DA recipients (>50 days). When LEW
      donors were treated with GdCl3, which is known to block Kupffer cell phagocytosis
      and antigen processing, the spontaneous acceptance of the LEW liver grafts by DA
      recipients was unaffected. However, when exogenous rhIL-2 was given daily, LEW
      liver allografts were rejected by the DA recipients. The resulting liver failure
      correlated with a progressive increase in serum bilirubin and the development of
      a predominantly lymphocytic portal tract infiltration, bile duct epithelial
      damage, and portal vein endothelitis, which is consistent with acute allograft
      rejection. LEW and DA recipients of liver isografts developed no toxicity and
      survived indefinitely (>100 days) when treated with the same dose of IL-2. These
      results indicate that spontaneous rat liver allograft acceptance is associated
      with the presence of radiosensitive cells in the donor liver that may interact
      with recipient T cells to inhibit (Th1) production of IL-2.

PMID- 9020315
TI  - Anti-GaL IgG antibodies in sera of newborn humans and baboons and its
      significance in pig xenotransplantation.
AB  - We have previously demonstrated that hyperacute rejection does not occur in a pig
      to-newborn baboon heart transplant model, presumably because of low levels of
      cytotoxic antipig antibodies present in the serum of newborn baboons. Cytotoxic
      antipig antibodies are primarily directed to alpha-1,3-galactosyl (alpha Gal)
      residues on endothelial cell surface structures Twenty-one full-term humans and 5
      full-term baboons were tested for complement mediated lysis (CML) of pig kidney
      (PK-15) cells and anti-alpha Gal activity with an ELISA using BSA-conjugated
      alpha Gal residues as target. To evaluate the significance of the anti-alpha Gal
      titers in vivo 5 newborn baboons underwent heterotopic pig cardiac
      xenotransplantation. Six of 21 human samples and 1 of 5 baboon samples
      demonstrated significant cytotoxicity to PK-15 cells. Twelve of 21 newborn humans
      had anti-alpha Gal IgG antibodies at titers of 1:80 or greater. None of the
      samples had anti-alpha Gal IgM. In newborn baboons, 1 of 5 sera had anti-alpha
      Gal IgG antibodies at titers greater than 1:80 and none of these samples had anti
      alpha Gal IgM. Xenografts survived for an average of 3.6 days, even in the baboon
      with high anti-alpha Gal IgG titers. Analysis of the explanted grafts showed
      minimal evidence of complement-mediated hyperacute rejection (HAR), but prominent
      mononuclear cell infiltrates. In serum tested posttransplant there was an induced
      anti-alpha Gal response with cytotoxicity against PK-15 cells. These results show
      that anti-alpha Gal IgM is absent in newborn human and baboon sera, allowing pig
      grafts to avoid HAR. However, the presence of anti-alpha Gal IgG may be
      associated with mononuclear cell infiltration of the xenograft and its subsequent
      rejection.

PMID- 9020316
TI  - The effect of small bowel transplantation on the morphology and physiology of
      intestinal muscle: a comparison of autografts versus allografts in dogs.
AB  - The effects of acute (AR) and chronic rejection (CR) on intestinal smooth muscle
      that are responsible for the dysmotility following small bowel transplantation
      (SBTX) are incompletely understood. Jejunal and ileal specimens from normal
      control dogs (n=7), and autotransplanted dogs were examined at 7 days (n=6) and 1
      (n=7), 3 (n=6), 6 (n=6), and 12 months (n=6). Allotransplanted dogs that
      developed AR (n=8) and CR (n=5) were examined for gross and microscopic
      morphology (muscle thickness, the number and size of myocytes, and inflammatory
      infiltrate), and for contractile and intracellular electrical function in vitro.
      Auto-SBTX did not alter morphology at any period, but contractile function was
      impaired at 7 days (73.6%) compared with normal intestine. Acute rejection did
      not influence myocyte number or size, but was associated with a prominent
      infiltrate of neutrophils and lymphocytes, and severely impaired contractile
      function (20.6%) compared with auto-SBTX controls. Acute rejection also
      significantly inhibited the amplitude of slow waves and of inhibitory junction
      potentials. Chronic rejection caused thickening of muscularis propria by both
      hyperplasia (175.5%) and hypertrophy (202.6%) accompanied by moderate
      inflammatory cell infiltrate compared with auto-SBTX controls. We conclude that
      the marked inflammatory infiltrate into the muscularis propria indicates that the
      graft muscle is injured by both acute and chronic rejection; impaired function of
      intestinal smooth muscle following SBTX results from both rejection and the
      injury associated with transplantation, and chronic rejection following SBTX is
      associated with both hyperplasia and hypertrophy of the muscularis propria.

PMID- 9020317
TI  - Renoprotective effects of the 21-aminosteroid U74389G in ischemia-reperfusion
      injury and cold storage preservation.
AB  - Free radical mediated lipid peroxidation (LPO) has been implicated in the
      pathogenesis of ischemic-reperfusion injury (IRI). To address the renoprotective
      effect(s) of LPO inhibition, the efficacy of the 21 aminosteroid U74389G was
      evaluated in three IRI models. In Model 1 51 unilateral nephrectomized rats that
      underwent 60 min of warm ischemia followed by a 72-hr reperfusion interval were
      treated with the test vehicle only, or 3, 6, or 12 mg/kg of U74389G
      intravenously, 5 min pre- or postischemia. In Model 2 Sprague-Dawley rats
      underwent sham operation (n=9), or 45 min of warm ischemia and 10 min of
      reperfusion with U74389G (6 mg/kg; n=10) or test vehicle only (n=10) administered
      intravenously over 10 min beginning 5 min prior to clamp release. After
      reperfusion, LPO was determined by assay of snap frozen tissue for thiobarbituric
      acid (TBA) concentrations (nmol/g tissue weight). In Model 3 domestic lean maid
      pigs (14-18 kg) underwent left nephrectomy with 30 min of warm ischemia, Collins
      C-4 flush, and 24 hr of cold storage preservation. Heterotopic
      autotransplantation and immediate contralateral nephrectomy was then performed in
      Group A-nonischemic controls (n=4), Group B-ischemic controls (n=5), and Group C
      U74389G (6 mg/kg) administered preischemia and at autotransplantation (n=5). In
      Model 1 maximal renoprotection was demonstrated with the 6 mg/kg dose of U74389G
      administered after ischemia (ischemic control 72-hr serum creatinine (Cr) =
      8.01+/-1.1 mg% vs. 3.32+/-0.96 mg%; ischemic control creatinine clearance =
      0.069+/-0.03 ml/min vs. 0.206+/-0.04 ml/min; P<0.05). In Model 2 TBA levels were
      significantly lower in U74389G treated animals (88.5+/-10.0 vs. ischemic controls
      = 296.8+/-81.4; P=0.02). In Model 3 graft survivals were 100%, 0%, and 60%
      respectively. Peak Cr and BUN (mg%) were significantly greater in Group C vs.
      Group A, (Group A Cr = 8.59+/-0.63 vs. Group C = 12.8+/-1.01; Group A BUN =
      64.1+/-2.73 vs. Group C = 104.9+/-12.21)--however, by day 10, thee were no
      significant differences in renal function: (Group A Cr = 2.15+/-0.3 vs. Group C =
      2.10+/-0.06; Group A BUN = 27.0+/-6.0 vs. Group C = 31.1+/-6.4). These results
      support the beneficial effects of LPO inhibitors in models of ischemia
      reperfusion, as well as preservation/transplantation, and suggest that this
      renoprotection correlates with decreased membrane lipid peroxidation.

PMID- 9020318
TI  - Comparison of various lazaroid compounds for protection against ischemic liver
      injury.
AB  - Lazaroids are a group of 21-aminosteroids that lack steroid action but have a
      potent cytoprotective effect by inhibiting iron-dependent lipid peroxidation.
      However, there have been conflicting reports on the effectiveness and potency of
      the various lazaroid compounds. In this study, we compared the effectiveness of
      three major lazaroids on warm liver ischemia in dogs using a 2-hr hepatic
      vascular exclusion model. The agents were given to the animals intravenously for
      30 min before ischemia. The animals were divided into 5 groups: Control (n=10),
      no treatment; Group F (n=6), U-74006F (10 mg/kg); Group G (n=6), U-74389G (10
      mg/kg); Group A1 (n=6), U-74500A (10 mg/kg); Group A2 (n=6), U-74500A (5 mg/kg).
      The effect of treatment was evaluated by two-week animal survival, hepatic tissue
      blood flow, liver function tests, blood and tissue biochemistry, and histological
      analyses. Animal survival in all treated groups was significantly improved
      compared with the control (83-100% versus 30%). Elevation of liver enzymes after
      reperfusion was markedly attenuated in treated groups, except for an early
      significant increase in Group G. Postreperfusion hepatic tissue blood flow was
      much higher in all treated animals (50% of the preischemic level vs. 25% in the
      control). Lazaroids, particularly U-74500A at 5 mg/kg (Group A2), suppressed
      adenine nucleotide degradation during ischemia and enhanced the resynthesis of
      high-energy phosphates after reperfusion. Although structural abnormalities in
      postreperfusion liver tissues were markedly ameliorated in all treated groups,
      Group A2 showed significantly less neutrophil infiltration. Liver injury from
      warm ischemia and reperfusion was attenuated with all lazaroid compounds, of
      which U-74500A at 5 mg/kg exhibited the most significant protective activity.

PMID- 9020319
TI  - Right ventricular failure--insights provided by a new model of chronic pulmonary
      hypertension.
AB  - This study was designed to examine the effects of both nitric oxide and milrinone
      on pulmonary hemodynamics and right ventricular function using a newly
      established model of monocrotaline pyrrole-induced chronic pulmonary
      hypertension. Sixteen mongrel dogs (23-25 kg) were used. All animals underwent
      percutanous pulmonary artery catheterization to measure right heart hemodynamics
      prior to and 8 weeks after a right atrial injection of either monocrotaline
      pyrrole (MCTP, n=8) or placebo (CTL, n=8). Eight weeks postinjection, all hearts
      were instrumented with a pulmonary artery flow probe and intracavitary
      micromanometers. Data were collected at baseline as well as following both nitric
      oxide and milrinone administration. There was no significant difference in the
      baseline hemodynamic measurements between the two groups. Eight weeks
      postinjection, significant increases in the pulmonary artery pressure and
      pulmonary vascular resistance were observed in MCTP compared with CTL. Both
      nitric oxide and milrinone resulted in significant improvements in pulmonary
      vascular resistance, pulmonary blood flow, and right ventricular contractility.
      In addition, nitric oxide caused a significant improvement in pulmonary artery
      pressure and transpulmonary efficiency, while milrinone led to a significant
      increase in right ventricular hydraulic power. This study demonstrates the well
      known clinical effects of nitric oxide and milrinone in improving pulmonary
      hypertension, which were also associated with an increase in pulmonary blood
      flow, transpulmonary efficiency, and right ventricular hydraulic power in the
      setting of monocrotaline pyrrole-induced chronic pulmonary hypertension.

PMID- 9020320
TI  - Attenuation of ischemic liver injury by augmentation of endogenous adenosine.
AB  - Hepatic grafts from non-heartbeating donors may alleviate the organ shortage, but
      they inherently suffer from warm ischemia. In the present study, we tested our
      hypothesis that augmentation of endogenous adenosine by inhibition of nucleoside
      transport with R75231 attenuates ischemic liver injury. Adult female beagle dogs
      underwent 2-hr hepatic vascular exclusion with venovenous bypass. R75231 was
      given to the animals by continuous intravenous infusion for 30 min before
      ischemia at a dose of 0.1 mg/kg (Group 2, n=6), 0.05 mg/kg (Group 3, n=6), or
      0.025 mg/kg (Group 4, n=6). Nontreated animals were used as the control (Group 1,
      n= 10). Animal survival, hepatic tissue blood flow, liver function, and
      histopathology were analyzed. Two-week animal survival was 30% in Group 1, 83% in
      Group 2, 100% in Group 3, and 100% in Group 4. Postreperfusion hepatic tissue
      blood flow was markedly improved by the treatment. Treatment significantly
      attenuated liver enzyme release, lipid peroxidation, and changes in adenine
      nucleotides and purine catabolites. Structural abnormality of the liver after
      reperfusion was markedly improved by R75231 treatment, showing better
      architecture and less neutrophil infiltration. Preischemic administration of a
      nucleoside transport inhibitor ameliorated ischemic liver injury due to the
      positive effects of augmented endogenous adenosine, and is applicable clinically
      when the liver is procured from a controlled non-heartbeating donor.

PMID- 9020322
TI  - Laparoscopic assisted live donor nephrectomy--a comparison with the open
      approach.
AB  - Live donor renal transplantation provides significant advantages when compared
      with cadaveric donor renal transplantation in terms of improved patient and graft
      survival, a lower incidence of delayed function, and a shorter waiting time. Yet
      despite these advantages, live donors continue to be an under utilized source of
      kidneys for transplantation. Disincentives to live donation include the length of
      hospitalization, postoperative pain, cosmetic concerns, and the prolonged
      convalescence associated with the donor operation. In many instances minimally
      invasive video-assisted techniques have proven more efficacious than standard
      open procedures in terms of patient discomfort, length of hospital stay, cost,
      and length of time until the patient can return to full activity. Laparoscopic
      live donor nephrectomies are being performed at our institution in an attempt to
      make live donation more attractive to the potential donor. The purpose of this
      study was to retrospectively review the results of laparoscopic live donor
      nephrectomy (LapNx) and to compare them with those obtained using the standard
      open approach (OpenNx). Ten consecutive LapNx were performed from February 1995
      through April 1996. The control group consisted of the 20 consecutive OpenNx
      performed at the same institution from January 1991 through January 1995
      immediately before the initiation of the LapNx program. Live donors were
      considered candidates for LapNx if they possessed at least one kidney with normal
      renal anatomy with single renal vessels and a single ureter. LapNx was safely
      performed in all cases. No patients required open conversion or blood
      transfusions. The allograft warm ischemic time for the laparoscopic cases was
      4.2+/-1.3 min. All kidneys harvested laparoscopically produced urine on the table
      immediately upon revascularization. Presently nine of the ten recipients have
      functioning allografts. At three months posttransplant the calculated recipient
      creatinine clearances were 67.0+/-11.5 ml/min and 64.8+/-21.4 ml/min for the
      LapNx and OpenNx groups, respectively (P=NS). The LapNx donors had a
      significantly decreased estimated blood loss, shorter time until resumption of
      oral intake, decreased postoperative pain (in terms of decreased analgesic
      requirements), shorter hospitalization, and a shorter interval until the
      resumption of full activities (P<0.05 for all). In addition, the LapNx group
      donors returned to work sooner than the OpenNx group (3.9+/-1.6 wk vs. 6.4+/-3.1
      wk, respectively) (P=0.024). Four individuals agreed to donate a kidney only
      after learning of the availability of the laparoscopic approach. We conclude that
      laparoscopic live donor nephrectomy is technically feasible. In addition, it may
      offer significant advantages over the standard open approach in terms of patient
      comfort and convenience. These advantages may make live donor renal
      transplantation more attractive to prospective donors. The potential decrease in
      hospitalization and convalescence may also prove to be financially advantageous.
      We believe that further careful study of this procedure is warranted.

PMID- 9020321
TI  - Tacrolimus rescue therapy for renal allograft rejection--five-year experience.
AB  - Over the 5 year period from 7/14/1989 until 5/24/1994, we have attempted graft
      salvage with tacrolimus conversion in a total of 169 patients (median age 33
      years, range 2-75 years) with ongoing rejection on baseline CsA immunosuppression
      after failure of high dose corticosteroids and/or antilymphocyte preparations to
      reverse rejection. The indications for conversion to tacrolimus were ongoing,
      biopsy confirmed rejection in all patients. The median interval to tacrolimus
      conversion was 2 months (range 2 days to 55 months; mean 4.3+/-2.6 months) after
      transplantation. All patients had failed high dose corticosteroid therapy and 144
      (85%) of the 169 patients had received at least one course of an antilymphocyte
      preparation plus high dose corticosteroid therapy prior to conversion. Twenty
      eight patients (17%) were dialysis-dependent at the time of conversion owing to
      the severity of rejection. With a mean follow-up of 30.0+/-2.4 months (median
      36.5 months, range 12-62 months), 125 of 169 patients (74%) have been
      successfully rescued and still have functioning grafts with a mean serum
      creatinine (SCR) of 2.3+/-1.1 mg/dl. Of the 144 patients previously treated with
      antilymphocyte preparations, 117 (81%) were salvaged. Of the 28 patients on
      dialysis at the time of conversion to tacrolimus, 13 (46%) continue to have
      functioning grafts (mean SCR 2.15+/-0.37 mg/dl) at a mean follow-up of 37.3+/
      16.7 months. In the 125 patients salvaged, prednisone doses have been lowered
      from 28.0+/-9.0 mg/d (median 32, range 4-60 mg/d) preconversion to 8.5+/-4.1 mg/d
      (median 12 mg/d, range 2.5-20 mg/d) postconversion. Twenty-eight patients (22.4%)
      are currently receiving no steroids. This 5 year experience demonstrates that
      tacrolimus has sustained efficacy as a rescue agent for ongoing renal allograft
      rejection. Based on these data, we recommend that tacrolimus be used as an
      alternative to the conventional drugs used for antirejection therapy in renal
      transplantation.

PMID- 9020323
TI  - Immunologic and patient selection strategies for successful utilization of less
      than 15 kg pediatric donor kidneys--long term experiences with 40 transplants.
AB  - Renal transplantation using infant donors is associated with significantly less
      graft survival (GS) and increased morbidity, especially from very young and small
      donors. We report our results using specific strategies to determine which age
      and size donor require en bloc renal transplant reconstruction and associated
      immunologic protocols for optimization of subsequent GS. Forty cadaveric
      pediatric en bloc renal transplants were performed. Mean donor age was 23.6+/
      18.4 months with subgroups: 2-12 months, n=14; 13-24 months, n=19; and 25-60
      months, n=7. Mean donor weight was 14.4+/-4.5 kg. All kidneys were placed in
      primary, nonsensitized (peak PRA = 7.9+/-5.6%) adult (41.6+/-16 years)
      recipients. Low weight was preferred (62.4+/-12.8 kg). Mean cold ischemia time
      was 26.9+/-8.6 hr. Immunosuppression consisted of quadruple immunosuppression
      (QI) with OKT3 induction. All patients had ureteral stents placed
      intraoperatively. Mean follow-up was 16.9 months. Actuarial GS at 12, 24, and 33
      months were 100% (n=13), 85% (n=20), and 71% (n=7), respectively. Total GS was
      35/40=88%. All grafts functioned immediately and there were no technical losses.
      Biopsy proven rejections occurred in 12 (30%) patients, developing at 16-167 days
      postoperatively (mean = 50.3 days). Mean serum creatinine at one week and 1, 6,
      12, and 18 months were 2.1+/-2.0, 1.5+/-0.8, 1.3+/-0.5, 1.1+/-0.4, and 0.9+/-0.4
      mg/dl, respectively. Functional isotopic renography, as well as sonographic
      monitoring reflected rapid initial and continued growth in these kidneys. Mean BP
      at 12 and 24 months postoperatively were 145/83+/-18/13 and 122/76+/-20/10 mmHg,
      respectively, with no significant proteinuria noted. Excellent results with
      minimal complications utilizing very small and young infant donors can be
      achieved with QI immunosuppression, and selection of low immune reactive and
      noncomplicated adult recipients. Additionally, maximal renal dosing by minimizing
      recipient weight may prevent future hyperfiltration damage.

PMID- 9020324
TI  - Simultaneous pancreas/kidney transplantation--a comparison of enteric and bladder
      drainage of exocrine pancreatic secretions.
AB  - Simultaneous pancreas/kidney transplantation (SPK) has evolved to become a
      therapeutic option for patients with renal failure resulting from type 1 diabetes
      mellitus. However, the appropriate route for drainage of the exocrine secretions
      of the pancreas allograft remains unclear. While bladder drainage (BD) is the
      current state of the art, it is associated with a high frequency of urologic
      complications, including urinary tract infections, hematuria, metabolic acidosis,
      dehydration, and reflux pancreatitis. Although enteric drainage (ED) is the more
      physiologic route, it has been associated in the past with decreased graft
      survival and increased infectious complications. In addition, BD offered a
      technique for detection of rejection through measurement of urinary amylase.
      However, with the advent of improved immunosuppression and antibiotic therapy,
      percutaneous pancreas biopsy, improved radiologic imaging, and greater
      understanding of pancreas transplantation, we hypothesized that ED could be
      performed without increased morbidity or cost. A group of 23 consecutive SPK was
      performed with ED during the period from July 1995 to November 1995. Another 23
      age- and sex-matched recipients of SPK with BD performed from November 1994 to
      June 1995 served as a historical control group. Because of the differing lengths
      of follow-up, data were analyzed with respect to the first six months
      posttransplant. ED and BD were associated with equivalent actuarial one-year
      patient and graft survival rates: 100% and 88% for ED, and 96% and 91% for BD,
      respectively. Hospital charges, length of stay, readmissions, rejection, sepsis
      related procedures were also equivalent in ED and BD. However, ED was associated
      with significantly fewer urinary tract infections and urologic complications. In
      addition, no grafts were lost as the result of sepsis. In the setting of SPK, ED
      represents a viable alternative to BD for primary drainage of pancreas exocrine
      secretions. Further studies with extended lengths of follow-up are necessary to
      confirm our observations.

PMID- 9020326
TI  - Hepatic artery stenosis after liver transplantation--incidence, presentation,
      treatment, and long term outcome.
AB  - Little is known about hepatic artery (HA) patency and patient clinical course
      when the nonthrombosed HA has been revised. We undertook this study to evaluate
      the risk factors in the development of HA stenosis and to assess the impact of HA
      revision on the outcome. A total of 857 adult consecutive OLT in 780 patients
      performed over a 6-year period were studied. Patients who underwent revision of
      their nonthrombosed but stenotic HA were reviewed for patient/graft survival,
      method of HA revision, incidence of biliary strictures, and long-term HA patency.
      Overall 39 patients (5%) with 41 allografts underwent HA revision for stenosis.
      Median time to diagnosis was 100 days posttransplant (range 1-1220 days). HA flow
      at the time of OLT was found to be the only significant variable of an
      anastomotic stenosis. No risk factor could be identified for the graft HA
      stenosis. Treatment methods included resection of the stenotic segment with
      primary reanastomosis (n = 17), aortohepatic iliac artery graft (n = 11),
      interposition vein graft (n = 4), vein patch angioplasty (n = 2), interposition
      artery graft (n = 1), and percutaneous transluminal balloon angioplasty (n = 6).
      Postrevisional HA patency was demonstrated in 32 (78%) cases. At a median follow
      up of 25 months, 26 patients (67%) were asymptomatic with good liver function.
      Nine patients had developed biliary strictures. Seven patients had undergone
      retransplantation and 8 patients had died. The actuarial patient and graft
      survivals at 4 years in the patients with revised HA were 65% and 56%,
      respectively. HA stenosis requiring revision is an infrequent occurrence after
      OLT. Long-term patency of the revised HA is good. Revision of the HA may help
      prevent biliary strictures and allow for good long-term graft function in the
      majority of patients.

PMID- 9020327
TI  - A statewide, population-based, time series analysis of access to liver
      transplantation.
AB  - While the number of patients listed for liver transplant has increased, the pool
      of donor organs has remained constant. Questions have arisen regarding equitable
      access to organs. The purpose of this study was to analyze factors associated
      with access to liver transplantation (LT) using a large, population-based,
      hospital discharge database. The primary hypothesis was that a variety of factors
      other than medical need could be associated with access to LT. The rate of LT was
      defined as the number of liver transplants per admission for liver disease. The
      data sources were selected to allow a population-based, time-series analysis of
      all patients admitted with liver disease and those receiving liver transplants in
      all 157 nonfederal hospitals in North Carolina from 1988 to 1993. The hypotheses
      of this study were that age, gender, payment source, type of liver disease,
      distance from the transplant center, and rural county of residence were
      associated with patients' likelihood of access to LT. During the six years
      studied, 56,803 patients were admitted with liver disease and 126 underwent liver
      transplantation (LT). The rate of LT increased from 0.07% to 0.27%. Age, gender,
      source of payment, type of liver disease, rural county of residence, and distance
      of residence from the transplant center were associated with rates of
      transplantation. In the multivariate model, source of payment appeared to have
      the strongest association with the likelihood of LT. These findings raise
      important questions associated with equitable access to health care, need for
      physician education, and transplant center regionalization.

PMID- 9020325
TI  - Weaning of immunosuppression in liver transplant recipients.
AB  - Immunosuppression has been sporadically discontinued by noncompliant liver
      allograft recipients for whom an additional 4 1/2 years of follow-up is provided.
      These anecdotal observations prompted a previously reported prospective drug
      withdrawal program in 59 liver recipients. This prospective series has been
      increased to 95 patients whose weaning was begun between June 1992 and March
      1996, 8.4+/-4.4 (SD) years after liver replacement. A further 4 1/2 years follow
      up was obtained of the 5 self-weaned patients. The prospectively weaned
      recipients (93 livers; 2 liver/kidney) had undergone transplantation under
      immunosuppression based on azathioprine (AZA, through 1979), cyclosporine (CsA,
      1980-1989), or tacrolimus (TAC, 1989-1994). In patients on CsA or TAC based
      cocktails, the adjunct drugs were weaned first in the early part of the trial.
      Since 1994, the T cell-directed drugs were weaned first. Three of the 5 original
      self-weaned recipients remain well after drug-free intervals of 14 to 17 years. A
      fourth patient died in a vehicular accident after 11 years off immunosuppression,
      and the fifth patient underwent retransplantation because of hepatitis C
      infection after 9 drug-free years; their allografts had no histopathologic
      evidence of rejection. Eighteen (19%) of the 95 patients in the prospective
      series have been drug free for from 10 months to 4.8 years. In the total group,
      18 (19%) have had biopsy proved acute rejection; 7 (7%) had a presumed acute
      rejection without biopsy; 37 (39%) are still weaning; and 12 (13%, all well) were
      withdrawn from the protocol at reduced immunosuppression because of noncompliance
      (n=8), recurrent PBC (n=2), pregnancy (n=1), and renal failure necessitating
      kidney transplantation (n=1). No patients were formally diagnosed with chronic
      rejection, but 3 (3%) were placed back on preexisting immunosuppression or
      switched from cyclosporine (CsA) to tacrolimus (TAC) because of histopathologic
      evidence of duct injury. Two patients with normal liver function died during the
      trial, both from complications of prior chronic immunosuppression. No grafts
      suffered permanent functional impairment and only one patient developed temporary
      jaundice. Long surviving liver transplant recipients are systematically
      overimmunosuppressed. Consequently, drug weaning, whether incomplete or complete,
      is an important management strategy providing it is done slowly under careful
      physician surveillance. Complete weaning from CsA-based regimens has been
      difficult. Disease recurrence during drug withdrawal was documented in 2 of 13
      patients with PBC and could be a risk with other autoimmune disorders.

PMID- 9020329
TI  - Pediatric lung transplantation--are there surgical contraindications?
AB  - Lung transplantation has evolved as a successful treatment for end-stage
      cardiopulmonary disease in children; however, clear guidelines regarding surgical
      exclusion criteria for pediatric lung transplant candidates have not been well
      established. Since December 1994, we have performed 10 bilateral lung transplants
      and 1 heart-lung transplant in 10 recipients (mean age, 7 years; range, 3 months
      to 19 years). Indications for transplantation included pulmonary vascular disease
      (n=6), bronchiolitis obliterans (n=2), bronchopulmonary dysplasia (n=1), graft
      failure due to viral pneumonitis (n=1), and cystic fibrosis (n=1). Among the 10
      patients, 4 were evaluated elsewhere for lung transplantation; of these, 3 were
      rejected by 1 or more programs because of "high-risk" characteristics. We
      considered 8 of the 10 patients to have 1 or more "high-risk" characteristics, as
      follows: previous chest operations other than open lung biopsy (n=6 patients
      having 1-4 previous operations), ventilator-dependence with tracheostomy and high
      dose corticosteroids (n=4), redo lung transplant (n=2), concomitant intracardiac
      repair (n=6), portal hypertension (n=1), and the use of extracorporeal membrane
      oxygenation (ECMO) at the time of transplant (n=1). Our standard operative
      approach was a bilateral thoracosternotomy. Cardiopulmonary bypass was used for
      explant of the recipient lungs and implant of the donor lungs, and during repair
      of coexisting congenital heart defects. Aprotinin and fresh whole blood were
      administered during the procedure to aid in hemostasis. Concomitant procedures
      were frequently performed and included repair of an intra-atrial baffle leak
      (prior Mustard procedure), closure of an atrial septal defect, repair of partial
      anomalous pulmonary venous return, reconstruction of the pulmonary venous
      confluence, ECMO decannulation, and splenectomy. There were no operative deaths,
      and no patient required re-exploration for bleeding. One patient had primary
      graft failure due to adenovirus infection of the donor lungs, and required
      prolonged mechanical ventilation and eventually ECMO support until
      retransplantation was performed. The mean hospital stay after transplant was 25+/
      13 days (range, 10-56 days). All patients were discharged with a natural airway.
      Airway complications consisted of one bronchial anastomotic stricture which
      required dilation, for a complication rate of 5% per anastomoses at risk. One
      patient required reoperation for stenosis of the superior vena cava. There have
      been no late deaths, with a mean follow-up of 7+/-4 months (range, 1-13 months).
      We attribute this 100% operative and short-term survival in these "high-risk"
      pediatric lung transplant recipients to our operative methods, a
      multidisciplinary approach to postoperative management, and the enormous
      physiologic reserve of pediatric patients. Therefore, the standard exclusion
      criteria used for adult lung transplantation may not be applicable to the
      pediatric age group. We hope to use these data to expand the use of lung
      transplantation in pediatric patients.

PMID- 9020328
TI  - Organ preservation solutions in heart transplantation--patterns of usage and
      related survival.
AB  - Despite experimental advantages for certain heart preservation solutions (HPS),
      their clinical popularity and related survival are uncertain. We surveyed all
      active UNOS heart transplant centers to determine their HPS. HPS survival
      benefits were tested using the UNOS heart transplant registry. Centers used from
      1 to 3 types of 167 solutions. Of these formulations, 55.1% were commonly cited
      solutions. The other (custom) mixtures differed from those usually reported. All
      solutions were classified as intracellular (I, [Na++] < 70 mEq/L) or
      extracellular (E, [Na++] > or = 70 mEq/L). Significant variations in solution
      usage were observed among major regions of U.S. transplant activity (Northeast
      [NE], Southeast [SE], and West [W], P < 0.001). For example, 62.5% of University
      of Wisconsin (UW) and 49.3% of "Other" usage occurred in the NE; 75% of Roe and
      100% of Collins usage occurred in the SE; and 100% of Krebs and 46% of Stanford
      usage occurred in the W. Logistic regression analyses of 9401 patients who
      underwent transplantation from 10/87 to 12/92 showed a reduction in the adjusted
      one month mortality odds ratio for grafts preserved with I rather than E
      solutions (0.85, P < 0.05). Compared with the most commonly used solution,
      Plegisol (20.1% of cases), the following adjusted odds ratios for one-month
      mortality were observed: UW, 1.09 (ns); Stanford, 0.80 (P < 0.10); Roe, 0.36 (P <
      0.001); Collins, 0.82 (ns); Krebs, 0.14 (P < 0.01). Using the same one month
      comparison with Plegisol, 16.8% of grafts that received Custom-I solutions also
      fared better (0.75, P < 0.05) than the 21.4% that had Custom-E mixtures (0.91,
      ns). HPS usage varies greatly and there are regional preferences. There may be
      early survival benefits for certain intracellular HPS--however, further study is
      warranted to explore such relationships.

PMID- 9020330
TI  - The role of PCR in the diagnosis and management of CMV in solid organ recipients:
      what is the predictive value for the development of disease and should PCR be
      used to guide antiviral therapy?
AB  - Cytomegalovirus remains a significant source of morbidity and mortality in
      immunocompromised hosts. The increased sensitivity of molecular diagnostic
      techniques (PCR, antigenemia) has resulted in our ability to detect viral
      replication earlier in the posttransplant period, before the onset of symptoms.
      With the advent of effective antiviral therapy, "preemptive therapy," guided by
      sensitive, early and specific predictors of CMV disease, has become a realistic
      objective. Although multiple studies have analyzed the sensitivity and
      specificity of these tests, their predictive value for the development of disease
      has not been defined. The purpose of this study was to evaluate the predictive
      value of a positive CMV PCR in the setting of solid abdominal organ
      transplantation. A total of 476 PCR assays were performed on 134 transplant
      recipients (102 kidney, 19 kidney/pancreas, 11 liver, 2 other) either as protocol
      serial samples or as dictated by clinical events. All samples were concomitantly
      analyzed using standard virological assays for CMV including culture, shell vial,
      and serology. Patients with any CMV seropositive donor/recipient (D/R)
      combination received ganciclovir prophylaxis in conjunction with antilymphocyte
      induction for 14 days. No subsequent CMV prophylaxis was used. The positive
      predictive value was 55% in all seropositive donor/recipient combinations. The
      highest risk group (seronegative recipient of seropositive donor) showed the
      highest positive predictive value, whereas seropositive recipients of either
      seropositive or seronegative donors showed positive predictive values of 45% and
      25%, respectively. Negative predictive value was 100% for all groups. Early
      detection of CMV infection has important implications for patient management,
      including preemptive therapy, which can be guided by PCR, especially in high risk
      (D+/R-) patients.

PMID- 9020331
TI  - Dependence of acquired systemic tolerance to rat islet allografts induced by
      intrathymic soluble alloantigens on host responsiveness, MHC differences, and
      transient immunosuppression in the high responder recipient.
AB  - Recent studies suggest that the adult immune system can be manipulated by
      intrathymic (IT) inoculation of donor Ag to accept cardiac and islet allografts
      in the low responder rat combination of Lewis-to-WF. We have now extended this
      study to examine the effect of IT inoculation of soluble protein Ag obtained from
      3M KCl extracts of resting T cells combined with transient ALS immunosuppression
      on islet allograft survival in the high responder combination of WF-to-Lewis. We
      first confirmed the earlier observation that IT injection of 2 mg soluble Ag on
      day -7 led to permanent islet graft survival (>200 days) in the Lewis-to-WF rat
      combination without the use of recipient immunosuppression and found this to be
      true in the Lewis-to-ACI rat combination. In the high responder combination of WF
      to-Lewis, unmodified Lewis rats pretreated with IT inoculation of 2 mg soluble Ag
      acutely rejected WF and BN islet allografts. IT inoculation of donor Ag combined
      with 1 ml ALS transient immunosuppression on day -7 led to a modest graft
      prolongation [24.8+/-10.1 days as compared with 15.2+/-3.6 days in ALS only
      treated controls]. Intrathymic injection of soluble Ag on day -7 combined with 1
      ml ALS on days -7 and 0 relative to allografting resulted in 100% permanent islet
      graft survival (>200 days) compared with an MST of 20.6+/-2.3 days in ALS only
      treated controls. Similar treatment led to acute rejection of 3rd party (BN)
      grafts, thus demonstrating donor-specificity. In addition, extrathymic
      inoculation of donor Ag in similarly immunosuppressed animals did not result in
      islet graft prolongation, once again confirming the importance of the thymus in
      tolerance induction. To examine them for donor-specific tolerance, long-term
      unresponsive (>120 days) Lewis recipients of renal subcapsular islets underwent
      nephrectomy of the islet bearing kidneys and were challenged with intraportal
      donor- or third party-type islets after becoming diabetic. All the
      nonimmunosuppressed recipients of donor-type (WF) islets became permanently
      normoglycemic (>100 days) while the third-party (BN) grafts were promptly
      rejected, with an MST of 10.6 days. These findings confirm that acquired thymic
      tolerance induced by IT inoculation of soluble protein Ag in the low to moderate
      responder rat combinations is reproducible in the high responder combination
      provided that adequate peritransplant immunosuppression is used. This study
      suggests that acquired thymic tolerance in the rat model is dependent on host
      responsiveness to alloantigens, MHC differences between the donor-recipient pair,
      and the use of transient immunosuppression in the high responder recipient. This
      model may have potential clinical application in the development of strategies
      for specific transplantation tolerance.

PMID- 9020332
TI  - Induction of donor specific transplantation tolerance to cardiac allografts
      following treatment with nondepleting (RIB 5/2) or depleting (OX-38) anti-CD4 mAb
      plus intrathymic or intravenous donor alloantigen.
AB  - The nondepleting monoclonal antirat CD4 antibody, RIB 5/2, has been shown to
      modulate, but not eliminate, the CD4+ T cells and to prolong survival of rat
      skin, renal, or cardiac allografts when serially administered after
      transplantation. In the present study, we compared the efficacy of recipient
      pretreatment with a single dose of nondepleting RIB 5/2 or depleting OX-38 anti
      CD4 monoclonal antibody plus donor alloantigen given intravenously or
      intrathymically 21 days before transplantation on the survival of completely MHC
      mismatched rat cardiac allografts. Intraperitoneal injection of a single dose (20
      mg/kg) of RIB 5/2 resulted in a decrease in CD4 surface molecule expression on
      peripheral CD4+ T cells without cell elimination as shown by FACS analysis. The
      nonspecific effect of a single dose of RIB 5/2 mAb had resolved by 21 days after
      treatment as evidenced by the almost complete recovery of normal surface CD4
      molecule expression. Cardiac allografts transplanted immediately or 21 days after
      a single dose of RIB 5/2 alone were uniformly acutely rejected. On the other
      hand, recipients treated with depleting anti-CD4 OX-38 (20 mg/kg) acutely
      rejected cardiac allografts transplanted 21 days later, but indefinitely accepted
      all grafts transplanted on the same day. In contrast, combined treatment with
      i.v. donor splenocytes (25 x 10(6)) plus nondepleting RIB 5/2, but not with
      depleting anti-CD4 mAb, OX-38, resulted in survival for more than 100 days in 75%
      of recipients of donor specific, but not third party, cardiac allografts
      transplanted 21 days later. Irradiation (3000 rads) of the i.v. donor splenocytes
      combined with RIB 5/2 abrogated their tolerizing effect. When donor antigen was
      given intrathymically, both RIB 5/2 and OX-38 resulted in indefinite tolerance to
      cardiac allografts transplanted 21 days later. The failure of exogenous
      administration of high dose (180,000 IU/injection) rIL-2 for 10 days to reverse
      the unresponsiveness of i.v. SC plus RIB 5/2 pretreatment suggests that this
      tolerant state is not due to a deficiency of IL-2. In vitro studies showed marked
      inhibition of MLC responsiveness and cytolytic T cell activity in tolerant
      recipients that cannot be reversed by the addition of IL-2. Thus, pretransplant
      intravenous donor alloantigen combined with a dose of nondepleting anti-CD4 mAb,
      RIB 5/2, which alone has no significant effect, induced donor specific cardiac
      allograft tolerance.

PMID- 9020333
TI  - Asialoglycoprotein/asialoglycoprotein receptor (AGP-AGPr) interaction is an
      important mechanism for the uptake of FK506 by hepatocytes.
AB  - Hepatic tissue concentrations of FK506 have been correlated with early acute
      rejection following liver transplantation. Asialoglycoproteins (AGP) reputedly
      bind FK506 in blood. AGP are removed from the circulation by the liver via the
      AGP receptor (AGPr), which resides on hepatocytes. This study was undertaken to
      determine if the AGP-AGPr mechanism enhances the delivery of FK506 to
      hepatocytes. Human orosomucoid (OM) was used as a representative AGP. asialoOM
      (aOM) was prepared by desialation of OM. Fresh rat hepatocytes were isolated by
      collagenase digestion. Tritium labeled FK506 (FK) was used to identify and
      quantitate FK506. Quantitation of FK in serum and culture media was by direct
      counting. FK in animal tissues used a method developed in our laboratory for the
      purpose. AGPr on resting hepatocytes was demonstrated by flow cytometry using
      FITC-orosomucoid and FITC-BSA controls. AGPr were enhanced by 2 g glucose/L. Two
      serum FK-binding fractions, 44 kD and 15 kD, were identified by gel filtration.
      Exogenous OM avidly bound FK and displaced FK activity from the 15 kD fraction.
      Serum (1%) and the 44 kD fraction enhanced the uptake of FK by hepatocytes, while
      serum depleted of OM-aOM by affinity chromatography was only 72.5% as effective
      as control serum; aOM enhanced the uptake of FK by hepatocytes to a degree
      similar to that of control serum but OM did not significantly affect the uptake
      of FK. Cold FK506 blocked the uptake and was dose dependent; cold CsA had no
      effect. Affinity extraction of OM from serum to which FK had previously been
      added removed 28.4% of FK activity. Following i.v. infusion, the kidney had the
      highest and liver the lowest tissue concentration of FK at 1 hr and 3 hr. In
      contrast, after oral administration the liver had the highest concentrations of
      the other tissues tested. The AGP-AGPr mechanism plays a significant role in the
      delivery of FK506 to hepatocytes and is likely responsible for the differences in
      bioavailability observed after oral and i.v. administration. Factors governing
      the AGP-AGPr mechanism are germane to understanding both the efficacy and
      toxicity of FK506 and the development optimal therapeutic strategies.

PMID- 9020334
TI  - Prevention of autoimmune islet allograft destruction by engraftment of donor T
      cells.
AB  - The results of clinical islet transplantation have remained poor when compared
      with the consistent success of pancreas transplantation. Autoimmunity has usually
      been discounted as a cause of islet transplant failure. Previously, we
      demonstrated that pancreas transplants from the diabetes resistant BB rat (BB-DR)
      function indefinitely in autoimmune diabetic hosts, but islets from the same
      donor are vulnerable to recurrent autoimmunity. Addition of 100 million
      pancreatic lymph node cells (PLNC) to BB-DR islets restores resistance to
      autoimmunity and leads to repletion of a T cell subset (RT6.1) in the recipients.
      Autoimmune (BB-Ac) and streptozocin (BB-Sz) diabetic BB rats were recipients of
      Wistar Furth (WF) intraportal islet or islets plus PLNC transplants with
      cyclosporine 5 mg/kg/day recipient treatment. One cohort of Brown Norway (BN)
      islet transplants to BB-Ac with CsA was performed. At the termination of the
      experiment, recipient peripheral blood lymphocytes (PBL) were characterized by
      flow cytometry (FACS) for class I, CD4, CD8, RT6.1, and RT6.2, a T cell
      maturation marker found in WF but not BB rats. All (14/14) WF and 75% (6/8) BN
      islet transplants to BB-Ac recipients failed after a mean of 42 and 36 days,
      respectively, despite CsA immunosuppression. WF islets were successful in 6/8
      (75%) transplants to BB-Sz recipients (P<0.001 vs. BB-Ac recipients), confirming
      that autoimmunity is the major cause of islet failure in BB-Ac rats. Addition of
      PLNC to WF islets increased the survival in BB-Ac to 82% (9/11) (P<0.0001 vs. WF
      islets alone). Recipients of islet+PLNC express 19.7% RT6.2 compared with 4.6%
      and 4.0% for WF islets alone in BB-Ac (P<0.01) and BB-Sz (P<0.01), respectively.
      Autoimmunity is an important factor leading to islet transplant failure in
      autoimmune diabetic BB rats. Addition of donor PLNC prevent islet allograft
      failure and leads to recipient chimerism for a donor T cell subset (RT6.2)
      associated with resistance to autoimmunity.

PMID- 9020336
TI  - Analysis of functional renal allograft tolerance with single-dose rapamycin based
      induction immunosuppression.
AB  - The induction of transplantation tolerance is one of the primary goals following
      solid organ transplantation. The combination of a single dose of rapamycin (RAPA)
      with a short course of cyclosporine (CsA) has been shown to induce
      transplantation tolerance in the nonfunctional rat heterotopic cardiac transplant
      model. The purpose of this study was to assess this effective induction protocol
      in a functional renal transplant model. Male ACI (RTl(a)) and Lewis (RT1(1)) rats
      were used as donor and recipients respectively. Allografts received a single RAPA
      dose of (1.5 mg/kg) combined with CsA (10 mg/kg) 12-14 hr prior to
      transplantation. CsA (5 mg/kg) was given daily on days +1 - +7. Untreated Lewis
      to Lewis isografts served as histological controls. Chimerism, assessed in
      recipient skin, and intragraft interleukin (IL) 10 expression was determined
      utilizing PCR and RT-PCR techniques respectively. Treated animals and isografts
      were sacrificed 120-130 days posttransplant for functional and histological
      evaluation. Allografts (n=9) were functionally tolerant with serum creatinine
      (0.77+/-0.1 vs. 0.88+/-0.1; P=0.275), blood urea nitrogen (37.6+/-4.6 vs. 23.3+/
      1.9; P=0.123), and 24 hr protein excretion (27.0+/-4.4 vs. 17.9+/-5.2; P=0.131)
      similar to single kidney ACI controls. Histologically, 45% (4/9) allografts were
      indistinguishable from isografts with no evidence of rejection, and were
      considered immunologically tolerant. Donor/recipient chimerism was not detected.
      All immunologically tolerant allografts had evidence of intragraft IL-10
      expression. Rejecting allografts and isografts did not express intragraft IL-10.
      This study confirms the efficacy of pre-engraftment single-dose RAPA combined
      with CsA in inducing true immunologic tolerance in this stringent functional
      renal transplant model. The expression of intragraft IL-10 in tolerant recipients
      suggests a Th-2 shift as the mechanism of tolerance in this model.

PMID- 9020335
TI  - Morphology of hDAF (CD55) transgenic pig kidneys following ex-vivo hemoperfusion
      with human blood.
AB  - Discordant xenotransplantation of pig kidneys into man may be possible in the
      future using transgenic organs which regulate complement activity. It was the aim
      of this experimental study to characterize morphologic alterations of organs
      transgenic for human decay accelerating factor (hDAF/CD55) perfused with human
      blood since no data on function of these organs after exposure to human blood are
      available. An ex-vivo system was developed that allows computer driven pressure
      controlled perfusion of kidneys including a separate cartridge oxygenator
      circuit. Following cold ischemia time of 1-4 hr, 8 kidneys from heterozygote
      transgenic animals (TG) and 9 control kidneys (C) were perfused with 500 ml
      freshly drawn heparinized human blood at physiological conditions. A histologic
      grading system from 0 to +4 was used to describe the histologic findings. Using a
      mouse antihuman DAF moAB, hDAF was stained on all TG kidneys both on glomerular
      capillary (4+) and vascular endothelium (2+), but there was no detectable hDAF
      expression on controls. No difference in xenoantibody deposition on vascular
      endothelium was seen between both groups. There was comparable staining for
      complement fraction C4 in both groups, but significant reduction of C3 and C9
      staining on glomerular and vascular endothelium in TG. P-selectin was expressed
      on a higher level in C (+4) compared with TG (+2). Neutrophil extravasation [NP
      57 elastase] was higher in C (80.2 vs. 32.2 C vs. TG [values as n/high power
      field]). Tubular epithelial cell swelling and mild necrosis was paralleled by
      glomerular hemorrhage and platelet microthrombus formation in both groups as seen
      in transmission electron microscopy. The observed results allow the conclusion
      that hDAF expression on transgenic pig kidneys was sufficient to inhibit
      complement activation beyond C3 during xenoperfusion with human blood despite
      xenoantibody deposition.

PMID- 9020337
TI  - Immunologic barriers to hepatic adenoviral gene therapy for transplantation.
AB  - Adenoviral gene transfer has potential use to attenuate the immunogenicity of
      hepatic allografts. However, the clinical application of adenoviral gene therapy
      is currently impeded by the potent host immune response to the virus that limits
      the duration of its effects. In these studies, we identify the cellular and
      humoral immune responses to recombinant adenovirus in the liver of mice and
      define the immunologic barriers to the successful application of this technology
      to transplantation. The immunobiology of recombinant adenovirus was studied in
      mouse liver using vectors containing the lacZ and alkaline phosphatase marker
      genes. The duration of transgene expression was studied in various
      immunodeficient mice to determine the mechanism of viral clearance. Adoptive
      transfer of serum to B lymphocyte deficient mice and neutralizing antibody assays
      were used to define the antiviral humoral response. Hepatic adenoviral transgene
      expression was prolonged in animals deficient in CD4+ or CD8+ T cells indicating
      their importance in viral clearance. Unexpectedly, mice lacking B lymphocytes
      also had delayed elimination of virus suggesting that B cells play a role in the
      primary immune response. Effective repeat gene transfer was blocked by adenoviral
      specific neutralizing antibody. Therefore, a T lymphocyte response results in
      viral elimination after a primary intravenous inoculation of recombinant
      adenovirus and a potent humoral response inhibits effective repeat adenoviral
      gene transfer. The immunogenicity of the vector must be overcome for adenoviral
      gene therapy to have therapeutic application for hepatic transplantation.

PMID- 9020338
TI  - Apoptosis in murine cardiac grafts.
AB  - Apoptosis, or the induction of programmed cell death, is a mechanism commonly
      used by cytotoxic T cells to cause target cell lysis. We evaluated the frequency
      and distribution of apoptotic cells in DBA/2-->DBA/2 heterotopic cardiac
      isografts, acutely rejecting DBA/2-->C57BL/6 cardiac allografts, and accepted, 60
      day DBA/2-->C57BL/6 allografts from mice treated with anti-CD4 Mab (GK1.5) or
      gallium nitrate (GN). Apoptosis was identified in histologic sections via TUNEL
      analysis of nuclear DNA fragmentation. We observed the following. (1) Cardiac
      isografts display no detectable TUNEL+ cells. (2) Rejecting cardiac allografts
      display rare (<1% of nucleated cells/field), diffuse TUNEL+ cells, peaking on day
      3 and declining to 50% of peak by the day of rejection (approximately day 10),
      and TUNEL+ cells were localized to regions of cellular infiltrate rather than
      myocyte regions. (3) Accepted cardiac allografts display relatively high numbers
      of TUNEL+ cells localized in and around the large cardiac arteries (about 20% of
      nucleated cells/periarterial field). These arteries often showed evidence of
      transplant vascular sclerosis characteristic of chronic allograft rejection.
      While a few TUNEL+ cells were found in the arterial tissue, most were observed in
      the periarterial cellular infiltrate. Similar frequencies and distributions of
      TUNEL+ cells were observed in grafts that were accepted due to treatment with the
      anti-CD4 mAb GK 1.5 or gallium nitrate. In general, apoptosis did not correlate
      with graft failure or parenchymal cell damage, suggesting that cytotoxic T cell
      mediated destruction of graft tissues is rare in cardiac allografts. While
      apoptosis does not appear to be indicative of acute rejection, the characteristic
      periarterial clustering of apoptosis in accepted grafts may be indicative of
      immunoregulatory processes that maintain graft acceptance or repair processes
      that promote chronic vascular remodeling.

PMID- 9020340
TI  - Avoid financial 'correctness'.

PMID- 9020339
TI  - The use of hibernation induction triggers for cardiac transplant preservation.
AB  - Cardiac transplant is hindered by donor shortage and preservation time. Extended
      extracorporeal preservation could increase the number and distribution of hearts
      for transplantation. Interestingly, mammalian hibernation biology closely
      parallels the altered cardiac cellular physiology noted with hypothermic organ
      storage. The present study undertook to test whether treatment with hibernation
      induction triggers could improve myocardial functional recovery following
      prolonged ischemic storage in a nonhibernating mammalian model. To study this
      hypothesis, isolated rabbit hearts had baseline functional and metabolic
      parameters recorded and then received either hypothermic storage only or standard
      cardioplegia, or cardioplegia containing 1 mg/kg D-Ala2-Leu5-enkaphalin (DADLE),
      which mimics natural hibernation, or preperfusion with DADLE, administered for 15
      min at 2 mmol, 25 min prior to cardioplegic ischemia. Hearts were then subjected
      to 18 hr of global ischemic storage at 4 degrees C. Isovolumic developed
      pressure, coronary flows, and myocardial oxygen consumption were significantly
      improved with DADLE pretreatment vs. all groups after storage and reflow.
      Furthermore, DADLE hearts demonstrated better histological ultrastructure
      preservation following prolonged storage ischemia. This study demonstrates that
      hibernation protection with DADLE is beneficial for prolonged cardiac storage.
      The use of hibernation induction triggers is promising for organ preservation and
      deserve further mechanistic study.

PMID- 9020341
TI  - Entire E. coli genome sequenced -- at last.

PMID- 9020342
TI  - UK seeks to appease food safety critics.

PMID- 9020343
TI  - AIDS 'cure' scientists go to top for funds.

PMID- 9020344
TI  - University teaching hospitals battle for scarce funds in Berlin.

PMID- 9020345
TI  - Mellow mood fosters marijuana research.

PMID- 9020346
TI  - Medical network pioneers live 3-D surgical images.

PMID- 9020347
TI  - Top FDA official named as 'de facto' chief.

PMID- 9020348
TI  - US urged to monitor some genetic tests.

PMID- 9020349
TI  - Darwin a better name than Wallace?

PMID- 9020350
TI  - A novel paradigm.

PMID- 9020351
TI  - Alternative therapy bias.

PMID- 9020352
TI  - How do memories leave their mark?

PMID- 9020353
TI  - How to keep a head in order.

PMID- 9020354
TI  - Alex Todd (1907-97)

PMID- 9020355
TI  - Synergy between synthetic oestrogens?

PMID- 9020356
TI  - HIV-1 tropism and co-receptor use.

PMID- 9020357
TI  - Female infertility in mice lacking connexin 37.
AB  - The signals regulating ovarian follicle development and the mechanisms by which
      they are communicated are largely undefined. At birth, the ovary contains
      primordial follicles consisting of meiotically arrested oocytes surrounded by a
      single layer of supporting (granulosa) cells. Periodically, subsets of primordial
      follicles undergo further development during which the oocyte increases in size
      and the granulosa cells proliferate, stratify and develop a fluid-filled antrum.
      After ovulation, oocytes resume meiosis and granulosa cells retained in the
      follicle differentiate into steroidogenic cells, forming the corpus luteum. It
      has been proposed that intercellular signalling through gap junction channels may
      influence aspects of follicular development. Gap junctions are aggregations of
      intercellular channels composed of connexins, a family of at least 13 related
      proteins that directly connect adjacent cells allowing the diffusional movement
      of ions, metabolites, and other potential signalling molecules. Here we show that
      connexin 37 is present in gap junctions between oocyte and granulosa cells and
      that connexin 37-deficient mice lack mature (Graafian) follicles, fail to ovulate
      and develop numerous inappropriate corpora lutea. In addition, oocyte development
      arrests before meiotic competence is achieved. Thus, cell-cell signalling through
      intercellular channels critically regulates the highly coordinated set of
      cellular interactions required for successful oogenesis and ovulation.

PMID- 9020358
TI  - Spatio-temporal frequency domains and their relation to cytochrome oxidase
      staining in cat visual cortex.
AB  - Spatial and temporal frequencies are important attributes of the visual scene. It
      is a long-standing question whether these attributes are represented in a
      spatially organized way in cat primary visual cortex. Using optical imaging of
      intrinsic signals, we show here that grating stimuli of different spatial
      frequencies drifting at various speeds produce distinct activity patterns. Rather
      than observing a map of continuously changing spatial frequency preference across
      the cortical surface, we found only two distinct sets of domains, one preferring
      low spatial frequency and high speed, and the other high spatial frequency and
      low speed. We compared the arrangement of these spatio-temporal frequency domains
      with the cytochrome oxidase staining pattern, which, based on work in primate
      striate cortex, is thought to reflect the partition of the visual cortex into
      different processing streams. We found that the cytochrome oxidase blobs in cat
      striate cortex coincide with domains engaged in the processing of low spatial and
      high temporal frequency contents of the visual scene. Together with other recent
      results, our data suggest that spatiotemporal frequency domains are a
      manifestation of parallel streams in cat visual cortex, with distinct patterns of
      thalamic inputs and extrastriate projections.

PMID- 9020359
TI  - Synaptic tagging and long-term potentiation.
AB  - Repeated stimulation of hippocampal neurons can induce an immediate and prolonged
      increase in synaptic strength that is called long-term potentiation (LTP)-the
      primary cellular model of memory in the mammalian brain. An early phase of LTP
      (lasting less than three hours) can be dissociated from late-phase LTP by using
      inhibitors of transcription and translation, Because protein synthesis occurs
      mainly in the cell body, whereas LTP is input-specific, the question arises of
      how the synapse specificity of late LTP is achieved without elaborate
      intracellular protein trafficking. We propose that LTP initiates the creation of
      a short-lasting protein-synthesis-independent 'synaptic tag' at the potentiated
      synapse which sequesters the relevant protein(s) to establish late LTP. In
      support of this idea, we now show that weak tetanic stimulation, which ordinarily
      leads only to early LTP, or repeated tetanization in the presence of protein
      synthesis inhibitors, each results in protein-synthesis-dependent late LTP,
      provided repeated tetanization has already been applied at another input to the
      same population of neurons. The synaptic tag decays in less than three hours.
      These findings indicate that the persistence of LTP depends not only on local
      events during its induction, but also on the prior activity of the neuron.

PMID- 9020360
TI  - Integrin-ligand binding properties govern cell migration speed through cell
      substratum adhesiveness.
AB  - Migration of cells in higher organisms is mediated by adhesion receptors, such as
      integrins, that link the cell to extracellular-matrix ligands, transmitting
      forces and signals necessary for locomotion. Whether cells will migrate or not on
      a given substratum, and also their speed, depends on several variables related to
      integrin-ligand interactions, including ligand levels, integrin levels, and
      integrin-ligand binding affinities. These and other factors affect the way
      molecular systems integrate to effect and regulate cell migration. Here we show
      that changes in cell migration speed resulting from three separate variables
      substratum ligand level, cell integrin expression level, and integrin-ligand
      binding affinity-are all quantitatively predictable through the changes they
      cause in a single unifying parameter: short-term cell-substratum adhesion
      strength. This finding is consistent with predictions of a mathematical model for
      cell migration. The ligand concentration promoting maximum migration speed
      decreases reciprocally as integrin expression increases. Increases in integrin
      ligand affinity similarly result in maximal migration at reciprocally lower
      ligand concentrations. The maximum speed attainable, however, remains unchanged
      as ligand concentration, integrin expression, or integrin-ligand affinity vary,
      suggesting that integrin coupling with intracellular motors remains unaltered.

PMID- 9020361
TI  - MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1.
AB  - Several members of the tumour-necrosis/nerve-growth factor (TNF/NGF) receptor
      family activate the transcription factor NF-kappaB through a common adaptor
      protein, Traf2 (refs 1-5), whereas the interleukin 1 type-I receptor activates NF
      kappaB independently of Traf2 (ref. 4). We have now cloned a new protein kinase,
      NIK, which binds to Traf2 and stimulates NF-kappaB activity. This kinase shares
      sequence similarity with several MAPKK kinases. Expression in cells of kinase
      deficient NIK mutants fails to stimulate NF-kappaB and blocks its induction by
      TNF, by either of the two TNF receptors or by the receptor CD95 (Fas/Apo-1), and
      by TRADD, RIP and MORT1/FADD, which are adaptor proteins that bind to these
      receptors. It also blocked NF-kappaB induction by interleukin-1. Our findings
      indicate that NIK participates in an NF-kappaB-inducing signalling cascade common
      to receptors of the TNF/NGF family and to the interleukin-1 type-I receptor.

PMID- 9020362
TI  - Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB.
AB  - The viability of vertebrate cells depends on survival factors which activate
      signal transduction pathways that suppress apoptosis. Defects in anti-apoptotic
      signalling pathways are implicated in many pathologies including cancer, in which
      apoptosis induced by deregulated oncogenes must be forestalled for a tumour to
      become established. Phosphatidylinositol-3-kinase (PI(3)K) is involved in the
      intracellular signal transduction of many receptors and has been implicated in
      the transduction of survival signals in neuronal cells. We therefore examined the
      role of PI(3)K, its upstream effector Ras, and its putative downstream protein
      kinase effectors PKB/Akt and p70S6K (ref. 5) in the modulation of apoptosis
      induced in fibroblasts by the oncoprotein c-Myc. Here we show that Ras activation
      of PI(3)K suppresses c-Myc-induced apoptosis through the activation of PKB/Akt
      but not p70S6K. However, we also found that Ras is an effective promoter of
      apoptosis, through the Raf pathway. Thus Ras activates contradictory
      intracellular pathways that modulate cell viability. Induction of apoptosis by
      Ras may be an important factor in limiting the expansion of somatic cells that
      sustain oncogenic ras mutations.

PMID- 9020363
TI  - The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are
      mutually dependent cofactors.
AB  - Nuclear hormone receptors and homeodomain proteins are two classes of
      transcription factor that regulate major developmental processes. Both depend on
      interactions with other proteins for specificity and activity. The Drosophila
      gene fushi tarazu (ftz), which encodes a homeodomain protein (Ftz), is required
      zygotically for the formation of alternate segments in the developing embryo.
      Here we show that the orphan nuclear receptor alphaFtz-F1 (ref. 3), which is
      deposited in the egg during oogenesis, is an obligatory cofactor for Ftz. The two
      proteins interact specifically and directly, both in vitro and in vivo, through a
      conserved domain in the Ftz polypeptide. This interaction suggests that other
      nuclear receptor/homeodomain protein interactions maybe important and common in
      developing organisms.

PMID- 9020364
TI  - The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain
      protein Ftz.
AB  - Homeobox genes specify cell fate and positional identity in embryos throughout
      the animal kingdom. Paradoxically, although each has a specific function in vivo,
      the in vitro DNA-binding specificities of homeodomain proteins are overlapping
      and relatively weak. A current model is that homeodomain proteins interact with
      cofactors that increase specificity in vivo. Here we use a native binding site
      for the homeodomain protein Fushi tarazu (Ftz) to isolate Ftz-F1, a protein of
      the nuclear hormone-receptor superfamily and a new Ftz cofactor. Ftz and Ftz-F1
      are present in a complex in Drosophila embryos. Ftz-F1 facilitates the binding of
      Ftz to DNA, allowing interactions with weak-affinity sites at concentrations of
      Ftz that alone bind only high-affinity sites. Embryos lacking Ftz-F1 display ftz
      like pair-rule cuticular defects. This phenotype is a result of abnormal ftz
      function because it is expressed but fails to activate downstream target genes.
      Cooperative interaction between homeodomain proteins and cofactors of different
      classes may serve as a general mechanism to increase HOX protein specificity and
      to broaden the range of target sites they regulate.

PMID- 9020365
TI  - How to find, identify and quantitate the sugars on proteins.
AB  - A new sequenator allows the identification, quantification and characterization
      of sites of glycosylation on proteins, making it possible to analyse the
      glycosylation at serine and threonine sites in mucin-like domains.

PMID- 9020366
TI  - Identification of an arginine452 to histidine substitution in the erythroid 5
      aminolaevulinate synthetase gene in a large pedigree with X-linked hereditary
      sideroblastic anaemia.
AB  - The coding region of the erythroid 5-aminolaevulinate synthetase gene (ALAS2)
      from a large pedigree with pyridoxine-responsive X-linked hereditary
      sideroblastic anaemia was examined for mutations. In three affected males from
      this pedigree, single strand conformational polymorphism (SSCP) analysis showed
      anomalous migration of a PCR product spanning exon 9. Sequencing of amplified
      genomic DNA from one of these affected males revealed a guanine to adenine
      transition at nucleotide 1407 of the cDNA sequence in exon 9 of the gene. This
      mutation results in the loss of an HhaI restriction enzyme digest site. An HhaI
      digest assay demonstrated the presence of this mutation in other affected males
      but not in unaffected males and unrelated individuals. The point mutation results
      in an arginine to histidine substitution at amino acid residue 452. The arginine
      residue is conserved in both the erythroid and housekeeping ALAS genes in all
      known vertebrate sequences. This arginine is located in the middle of a predicted
      alpha-helix.

PMID- 9020367
TI  - Clonal CD8+ and CD52- T cells are induced in responding B cell lymphoma patients
      treated with Campath-1H (anti-CD52).
AB  - Five patients with non-Hodgkin's lymphoma (NHL) and 4 patients with chronic
      lymphocytic leukaemia (CLL) were treated with the CDR-grafted (rat x human)
      monoclonal antibody (mAb) Campath-1H (anti-CD52). Tumour regression was noted
      preferentially in peripheral blood and in the bone marrow but lymph nodes were
      less affected. Normal blood B and T cells were profoundly reduced in all patients
      whereas CD16+ NK cells and CD14+ monocytes decreased marginally. In all
      responding CLL patients CD52-negative T but not B cells appeared during treatment
      and persisted for several months (4-19+) during unmaintained follow-up. Clonal T
      cells defined as a predominance of a single T cell receptor (TCR) V gene usage,
      in one case verified by TCR CDR3 fragment analysis and nucleotide sequencing,
      emerged within the CD52-/CD8+ cell population during Campath-1H therapy in 2 CLL
      patients, both achieving a long-lasting remission. The increase in CD8+ T cell
      expansions (up to 23-fold) during unmaintained remission and follow-up suggest
      that the clonal CD8+ cells may represent regulatory T cells controlling the
      growth of the tumour B cell clone. Clonal T cells might thus be a target for an
      immune therapeutic intervention in B cell tumours.

PMID- 9020368
TI  - Relationship between the severity of beta-thalassaemia syndromes and the number
      of alleviating mutations.
AB  - Thalassaemia intermedia, defined as homozygous beta-thalassaemia in which
      patients are not transfusion-dependent, covers a wide range of clinical severity.
      It may arise because one or more genetic factors ameliorate the otherwise severe
      phenotype of thalassaemia major. Exactly which and how many such mutations are
      necessary to produce a thalassaemia intermedia phenotype is incompletely
      understood, although such information would be useful both clinically and for
      prenatal diagnosis. We examined DNA from 28 patients with thalassaemia intermedia
      resident in London and 28 matched patients with thalassaemia major, for 3 types
      of genetic modifying factors, namely; mild beta-thalassaemia mutations, the
      upstream XmnI G-gamma globin gene polymorphism, and alpha-globin gene deletions.
      The results show that the number of alleviating mutations present has a large
      influence on the phenotype of patients with homozygous beta-thalassaemias. A
      single alleviating mutation was present in 56% of thalassaemia intermedia
      subjects compared with 26% of thalassaemia major subjects. Two alleviating
      mutations were present in 33% of thalassaemia intermedia subjects compared with 1
      thalassaemia major subject. No patients with thalassaemia major had 3 alleviating
      mutations, in contrast to 11% of those with thalassaemia intermedia. Although the
      findings did not account for the full range of phenotypic variation, such
      information is of potential value both in the clinical management and the
      prenatal diagnosis of homozygous beta-thalassaemia.

PMID- 9020369
TI  - Administration of high doses of recombinant human erythropoietin to patients with
      beta-thalassemia intermedia: a preliminary trial.
AB  - Four patients (1 male, 3 female, age range 16-56 yr) with beta-thalassemia
      intermedia were given high doses of recombinant human erythropoietin (rHuEpo),
      iron sulfate and folic acid in an attempt to improve their anemia. The dose
      schedule was: rHuEpo, 500 U/kg 3 times weekly, iron sulfate, 300 mg/d and folic
      acid, 5 mg/d. All patients were red blood cell transfusion-dependent.
      Hematological data and fetal hemoglobin (HbF) were assayed every 2 wk. XmnI
      polymorphism and beta-thalassemia mutations were identified by PCR. All patients
      showed a moderate to high increase in hemoglobin values (mean value: 2.5 g/dl)
      and in 1 patient HbF levels also increased; 3 patients became red blood cell
      transfusion-independent and 1 patient was able to extend the intervals between
      transfusions significantly. No side effects were observed during rHuEpo therapy.

PMID- 9020370
TI  - High-dose methylprednisolone for children with acute lymphoblastic leukemia and
      unfavorable presenting features.
AB  - In an attempt to improve treatment outcome high-dose methylprednisolone (HDMP, 20
      30 mg/kg, once a day orally) was used instead of a conventional dose of steroid
      (2 mg/kg/d, in 3 divided doses) in children with acute lymphoblastic leukemia
      (ALL) with increased risk factors. HDMP combined with cytotoxic agents
      (vincristine and L-asparaginase) resulted in an improved complete remission rate
      (94%) in 48 newly diagnosed children with ALL compared to 81% in 86 historical
      controls receiving standard dose steroid combined with the same treatment
      regimen. The bone marrow relapse rate was lower in patients who received HDMP
      (31%) than in controls (56%). Treatment was discontinued in 56% of 48 patients
      receiving HDMP and in 35% of 86 controls. The difference was significant (p <
      0.05). The 5-yr continuous complete remission rate was significantly greater in
      patients received HDMP compared with the control patients (60% vs. 43%, p <
      0.05). HDMP treatment was well tolerated without significant adverse effects.
      Moreover, during induction therapy the duration of leukopenia (< 2 x 10(9)/L) was
      shorter in patients receiving HDMP. We conclude that HDMP combined with other
      antileukemic agents increased the CR rate and prolonged the duration of remission
      in children with ALL who had increased risk factors. However, the optimal dosage
      of HDMP and its role in maintenance therapy should be determined in future,
      randomized studies.

PMID- 9020371
TI  - Adhesion molecule CD11a/CD18-deficient Burkitt's lymphoma cells lack the
      transcript for the beta, but not the alpha, integrin subunit.
AB  - Adhesion to cells and matrices participates in the regulation of lymphocyte
      proliferation, maturation and tissue localization. Consequently, abnormal
      patterns of adhesion molecule expression may contribute to the pathophysiology of
      lymphoproliferative disorders. Integrins are major cell-surface adhesive proteins
      composed by alpha and beta subunits. In contrast to normal lymphocytes, Burkitt's
      lymphoma (BL) cells lack the beta2 integrin CD11a/CD18. To study the molecular
      mechanism underlying this deficiency, presence of the transcript for each subunit
      was analysed by Northern blotting in group I BL lines (BL biopsy-like) and, for
      comparison, Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines
      (LCLs). While transcripts for both CD11a (alpha subunit) and CD18 (beta subunit)
      were readily detected in LCLs, BL lines contained the transcript for the alpha
      subunit only. Treatment of BL cells with phorbol ester for 72 h induced
      expression of the beta subunit mRNA and the CD11a and CD18 antigens on the cell
      surface. The results indicate that the CD11a/CD18 deficiency of BL is due to
      absence of the beta subunit transcript and that this defect is restored by
      stimulation of the cells.

PMID- 9020372
TI  - Chronic isolated macrothrombocytopenia with autosomal dominant transmission: a
      morphological and qualitative platelet disorder.
AB  - We studied 47 subjects belonging to 13 unrelated families with a history of mild
      haemorrhagic diathesis and chronic thrombocytopenia. 36 patients presented some
      degree of thrombocytopenia: 7/36 (19%) had slight thrombocytopenia (100-150 x
      10(9)/L); 26/36 (72%) had mild thrombocytopenia (50-100 x 10(9)/L) and 3/36 (8%)
      had severe thrombocytopenia (< 50 x 10(9)/L). No correlation was observed between
      platelet count and the degree of haemorrhagic diathesis, which was mild in the
      majority of patients. Transmission was autosomal dominant. Platelet anisocytosis,
      increased percentage of large platelets and absence of leukocyte inclusions were
      observed in 26/30 (87%) of the examined blood smears. The ultrastructural
      appearance of platelets was normal. Megakaryocytes appeared normal in number in
      10/10 patients, but showed asynchronous nuclear-cytoplasm maturation and mainly
      nonlobulated nuclei. Platelet aggregation was studied in 26 patients and either
      increased or decreased curves were variably observed in response to different
      aggregating agents. Platelet-associated IgG (PAIgG) was increased in 18/31 (58%)
      patients, while serum autoantibodies against platelet glycoproteins Ib/IX or
      IIb/IIIa were demonstrable in only 1 case. An increased expression of platelet
      surface glycoproteins Ib and IIb/IIIa, as studied by murine monoclonal antibodies
      binding in 17 cases, was observed. Platelet survival performed by 111Inoxine
      labelled autologous platelets was normal in the 3 studied patients. Congenital
      macrothrombocytopenia confirms to be a distinct clinical disorder for which the
      name of "chronic isolated hereditary macrothrombocytopenia" is proposed.

PMID- 9020373
TI  - 2-Chlorodeoxyadenosine in the treatment of relapsed/refractory chronic
      lymphoproliferative disorders.
AB  - 2-Chlorodeoxyadenosine (2-CdA) is a purine analog with cytotoxic activity on both
      resting and cycling lymphocytes which has been used as salvage therapy in
      advanced/resistant chronic lymphoproliferative disorders. In our study 39
      patients (19 B-CLL, 5 B-PLL, 9 low-grade B-NHL, 5 CTCL and 1 high-grade T-NHL)
      who relapsed or became resistant after 1-4 chemotherapy regimens were treated
      with 2-CdA 6 mg/m2 per day by 2 h infusion for 5 d every 28 d. The overall
      clinical response rate, including complete remission (CR) and partial remission
      (PR), was 66%. Two of 19 (10%) B-CLL patients achieved a CR lasting 9 months,
      while 11/19 B-CLL (58%) and 4/5 B-PLL (3 B-PLL/B-CLL and 1 B-PLL) (80%) achieved
      a PR. Interestingly, 5 of 6 patients who had been previously treated with
      fludarabine obtained a clinical response (2 CR and 3 PR). One of 9 (11%) low
      grade B-NHL patients achieved a CR and relapsed after 26 months, and 5/9 (55%)
      achieved a PR. One of 5 (20%) CTCL achieved a CR lasting 32 months, while 2/5
      (40%) achieved a PR. The overall mean duration of PR was 7.4 months and no
      differences were observed among different groups of patients. Toxicity was
      acceptable, as only a transient severe hematological impairment was observed in
      20% of the patients while nonhematological toxicity was not documented. Two
      patients died because of bacterial pneumonia, 1 of meningitis due to Listeria and
      9 from progression of the disease. In conclusion, treatment with 2-CdA in heavily
      pretreated patients with chronic lymphoproliferative disorders is well tolerated
      and obtains high response rates, even in patients relapsed after treatment with
      fludarabine.

PMID- 9020374
TI  - Elevated levels of soluble thrombomodulin in plasma from children with Arg 506 to
      Gln mutation in the factor V gene.
AB  - To find out to what extent the Arg506 to Gln mutation in the factor V gene
      affects the defence system against thromboembolism we investigated soluble
      thrombomodulin, protein C, protein S along with thrombin generation and D-dimer
      formation in 188 children. Children with the Arg506 to Gln mutation in the factor
      V gene (n = 48) showed significantly elevated thrombomodulin concentrations
      compared to nonaffected brothers and sisters (n = 50; p = 0.001) and age-matched
      healthy controls (n = 90; p < 0.0001). In addition, thrombin generation and D
      dimer formation were significantly elevated in children with the mutation. In
      contrast, protein C and total protein S antigen levels were no different in the
      populations tested. Thus, with respect to thrombomodulin being a potent inhibitor
      of coagulation activation, the present data might be interpreted as a
      counterregulatory mechanism in infants and children with the Arg506 to Gln
      mutation in the factor V gene, maintaining the coagulation balance. The role of
      TM and other proteins involved in the coagulation balance in children and adults
      homozygous for the Arg506 to Gln mutation in the factor V gene remains to be
      clarified.

PMID- 9020375
TI  - Ultrastructural localization of Charcot-Leyden crystal protein in human
      eosinophils and basophils.
AB  - The Charcot-Leyden crystal (CLC) protein with lysophospholipase activity and
      carbohydrate-binding properties is a characteristic constituent of eosinophils
      and basophils. We investigated its subcellular distribution using immunoelectron
      microscopy. Eosinophil progenitors, mature eosinophils and basophils all
      contained CLC protein in their cytosol and in the euchromatin of the nucleus. A
      minor population of granules in eosinophils, increasing in number with
      maturation, and a more abundant granule-population in basophils, were found to
      contain CLC protein. Double-labeling experiments showed, in eosinophils, that CLC
      protein-containing granules contain also eosinophil peroxidase, a characteristic
      specific granule protein. This suggests a relationship between the CLC protein
      containing organelle and the specific granule. In basophils both the CLC protein
      positive and the negative granules showed the same characteristic particulate
      like structure of the granular matrix and both share the same membrane marker
      CD63. In nasal polyps, macrophages were observed phagocytosing necrotic
      eosinophils. In these macrophages CLC protein-containing vesicles were observed,
      probably representing late endosomes. The dual (cytosolic/nuclear and granular)
      localization of CLC protein suggests that this protein enters both a secretory
      and a nonsecretory pathway during its biosynthesis, indicating functional roles
      for this protein both within the cell and extracellularly.

PMID- 9020376
TI  - A mild form of Hb S-beta-thalassemia syndrome is assured in Sicilian patients by
      beta+mutant IVS-I nt 6(T-->C)

PMID- 9020377
TI  - Wingless armadillos and their clinical relevance.

PMID- 9020378
TI  - Bioinformatics and molecular medicine--introduction and call for papers.

PMID- 9020379
TI  - The ubiquitin-mediated proteolytic pathway as a therapeutic area.
AB  - Ubiquitin-mediated proteolysis is involved in the turnover of many short-lived
      regulatory proteins. This pathway leads to the covalent attachment of one or more
      multiubiquitin chains to target substrates which are then degraded by the 26S
      multicatalytic proteasome complex. Multiple classes of regulatory enzymes have
      been identified that mediate either ubiquitin conjugation or ubiquitin
      deconjugation from target substrates. Timed destruction of cellular regulators by
      the ubiquitin-proteasome pathway plays a critical role in ensuring normal
      cellular processes. This review provides multiple examples of key growth
      regulatory proteins whose levels are regulated by ubiquitin-mediated proteolysis.
      Pharmacological intervention which alters the half-lives of these cellular
      proteins may have wide therapeutic potential. Specifically, prevention of p53
      ubiquitination (and subsequent degradation) in human papilloma virus positive
      tumors, and perhaps all tumors retaining wild-type p53 but lacking the
      retinoblastoma gene function, should lead to programmed cell death. Specific
      inhibitors of p27 and cyclin B ubiquitination are predicted to be potent
      antiproliferative agents. Inhibitors of IkappaB ubiquitination should prevent
      NFkappaB activation and may have utility in a variety of autoimmune and
      inflammatory conditions. Finally, we present a case for deubiquitination enzymes
      as novel, potential drug targets.

PMID- 9020380
TI  - Inhibition of MHC class I antigen presentation by viral proteins.
AB  - An essential part of the immune response to viral infections is the recognition
      and elimination of infected cells by cytotoxic T lymphocytes. For this purpose a
      display mechanism has evolved which is present in almost all nucleated cells: the
      major histocompatibility complex class I antigen processing pathway. Both self
      and foreign antigens are degraded in the cytosol to peptides which are
      translocated into the endoplasmic reticulum where they are loaded onto MHC class
      I molecules. Pathogens living inside the cell are evolving under the constant
      selection pressure of such immune surveillance. As a result such infectious
      organisms have developed a variety of strategies to prevent their antigens from
      being presented. Since our understanding of the cell biology of antigen
      presentation has greatly advanced in recent years, it has now become possible to
      unravel several of the molecular mechanisms by which viruses interfere with MHC
      class I antigen presentation. Examples for the interference of viral molecules
      with components of the MHC class I pathway are presented in this review.

PMID- 9020381
TI  - Kaposi's sarcoma: is the hunt for the culprit over now?
AB  - Patients suffering from the acquired immune deficiency syndrome (AIDS) have a
      20000-fold increased risk of developing a severe form of Kaposi's sarcoma (KS), a
      previously rare malignancy involving sharply defined nodular lesions of the skin
      and/or oral mucosa. Epidemiological evidence has long suggested that an
      infectious agent is the probable cause of KS. Recently sequences from a putative
      new herpesvirus have been found to be associated with KS in virtually 100% of the
      cases analyzed. The suspected etiological agent, a new human herpesvirus termed
      Kaposi's sarcoma associated herpes virus (human herpes virus 8) has now been
      propagated in cell culture. This significant advance should form the basis for a
      detailed analysis of the pathogenetic mechanisms involved in the development of
      KS.

PMID- 9020382
TI  - Protein kinase mediators of integrin signal transduction.
AB  - Protein kinases are important mediators of signal transduction initiated by
      soluble growth factors and cytokines. Cellular interactions with the
      extracellular matrix are mediated largely by members of the integrin class of
      cell adhesion molecules, which also subsume signal transduction functions
      required for cell growth, differentiation, and survival. Here we review the
      involvement of protein kinases in mediating integrin intracellular signal
      transduction and the possible role for these molecules in regulating integrin
      adhesion. Although in most cases mechanistic details are incomplete, the emerging
      theme of protein kinases mediating cross-talk between growth factor receptor and
      integrin signalling systems provides a timely backdrop against which to present
      new developments in this area. The contribution of the actin cytoskeleton to
      integrin signal transduction is discussed, with respect to the concept of 'solid
      state' signalling providing a mechanism for imposing order on the protein-protein
      interactions which underlie signal discrimination. Moreover, we review evidence
      that dysregulated integrin signalling contributes to pathological processes
      including arthritis, thrombasthenia, leucocyte adhesion deficiencies, and tumour
      angiogenesis and invasion.

PMID- 9020383
TI  - Telomerase activation and cancer.
AB  - Normal human cells have a limited life span in culture. It is generally believed
      that progression of cells to malignancy requires an overriding of this natural
      program of cellular senescence. An understanding of the genes controlling
      senescence will likely be valuable in determining the underlying mechanisms of
      abnormal cell growth and carcinogenesis. The hypothesis that telomeres play an
      integral role in cell senescence and immortalization has recently received much
      attention. This review discusses some of the current literature pertaining to how
      telomeres and activation of telomerase, a ribonucleoprotein that synthesizes
      telomere repeats, are believed to be involved in the process of immortalization.
      It also discusses how a further understanding of the telomerase enzyme may lead
      to better diagnostic and treatment strategies for a variety of cancer types.

PMID- 9020384
TI  - Germline p53 mutation at codon 133 in a cancer-prone family.
AB  - We identified four families in which we suspected the presence of genetic factors
      predisposing them to cancer. We examined one family with features suggesting Li
      Fraumeni syndrome for the presence of a germline p53 mutation in 13 of its
      members. To detect germline p53 mutations we performed polymerase chain
      reaction/nonradioisotopic single-strand conformation polymorphism and DNA
      sequencing analysis on exons 4-9 of the p53 gene. Mutated polymerase chain
      reaction-restriction fragment length polymorphism analysis was also performed on
      exon 5 to confirm the mutation identified by the sequencing analysis. A novel
      germline p53 mutation was identified at codon 133 (ATG-->AGG) in exon 5,
      resulting in the substitution of arginine for methionine, in all four cancer
      affected individuals and in three apparently healthy individuals. We also
      analyzed tumor specimens for additional p53 mutations in the wild-type alleles
      using the same methods. However, heterozygosity was retained, and no other
      additional mutations in the wild-type allele were identified in any of the tumor
      tissues. It is possible that additional mutations in the wild-type allele are not
      always necessary for the loss of tumor suppressor functions. This study presents
      serious clinical and ethical problems about the predictive value of identifying
      germline p53 mutations in presymptomatic carriers. However, accurate predictive
      testing will be very useful in identifying unaffected individuals who are at
      increased risk of developing cancer and in detecting cancer at an early stage.

PMID- 9020385
TI  - Relationship of polymorphisms in the renin-angiotensin system and in E-selectin
      of patients with early severe coronary heart disease.
AB  - Previous association studies between angiotensin-converting enzyme (ACE) and
      angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have
      reported variable results. Therefore we examined the association of the DNA
      variants of ACE and AGT with early, severe coronary heart disease (CHD). In
      addition, we compared the genotypes of both polymorphisms and the recently
      discovered polymorphism in the E-selectin gene in both patients and an unselected
      population. This study included 113 patients with severe CHD (50 years old or
      less) and up to 197 control subjects. The frequencies of the ACE I/D variants
      were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The
      frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls
      and 49.1% M and 50.9% T in the patients. The frequencies of the S128R
      polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S
      and 15.5% R in the patients. In our studies the DD genotype of ACE was not
      associated with early severe CHD. We found a correlation between the M235T
      molecular variant of AGT and the S128R variant of E-selectin to early severe CHD.

PMID- 9020386
TI  - Investigation of the Met-267 Arg exchange in isoform 1 of the human plasma
      membrane calcium pump in patients with essential hypertension by the
      amplification-created restriction site technique.
AB  - Alterations in Ca2+ homeostasis have been proposed to be a primary factor in the
      pathogenesis of essential hypertension. In this disease increased intracellular
      Ca2+ levels have repeatedly been reported in various cell types. Because of its
      prominent role in cellular calcium homeostasis in vascular smooth muscle cells,
      modifications of the plasma membrane Ca2+-ATPase (PMCA) pump have been suggested
      to contribute to an increased contractile tone of small blood vessels. This pump
      is a calmodulin-dependent Ca2+-ATPase that ejects Ca2+ from the cytosol into the
      extracellular space. Recently a mutational thymidine (T)-->guanosine (G)
      transversion in isoform 1 of the PMCA has been identified resulting in the
      substitution of a methionine (Met) by an arginine (Arg) at amino acid position
      267 in a highly conserved domain of the pump molecule. The aim of our study was
      to determine the prevalence of this polymorphism in the normal population and to
      investigate whether the Met-267 Arg occurs more frequently in patients with
      essential hypertension than in normotensives. To detect the mutational change we
      modified a method based on the technique of amplification-created restriction
      sites (ACRS) using three base exchanges in the diagnostic primer. Samples from
      100 hypertensive and 60 normotensive subjects revealed a thymidine at nucleotide
      position 981. These data suggest that ACRS is feasible in spite of extensive
      primer modifications (e.g., three mismatched bases) in contrast to the previously
      used one or two and may therefore be conceptually suitable to detect almost any
      base changes in the genome. The described T-->G transversion is a rare
      polymorphism and is presumably not related to common forms of essential
      hypertension.

PMID- 9020387
TI  - Neocortical temporal lobe sclerosis masquerading as Alzheimer dementia: does
      herpes virus encephalopathy protect against Alzheimer's disease?
AB  - Semi-quantitative neuropathological analysis and morphometric evaluations of the
      brains of 5 elderly people (63-85 years old) dying following a 5-27-year history
      of dementia reveal that, despite exhaustive survey of all major brain regions, 4
      of these cases show virtually no histopathological lesions of Alzheimer's
      disease. Instead their CNS manifests a severe, bilateral, neuronal depletion, and
      astrogliosis afflicting the lateral temporal neocortex, highly compatible with a
      previous herpetic viral encephalitis. In the fifth case unilateral neocortical
      temporal lobe sclerosis is accompanied by Alzheimer's disease, but with much more
      dense Alzheimer lesions throughout the contralateral cerebral hemisphere. Three
      of these 5 individuals had a history either of herpes zoster of the skin or of a
      single episode of viral meningoencephalitis, roughly concomitant with the onset
      of memory loss. This clinical and pathological evidence that a remote herpes
      virus encephalopathy (when bilateral) "protects" that brain against Alzheimer's
      disease strengthens our growing suspicion that incomplete replication cycles of
      herpes simplex or zoster virus, following repeated reactivation within neurons of
      the trigeminal ganglia, may link these viruses to the pathogenetic cascade
      underlying dementia of the Alzheimer type.

PMID- 9020388
TI  - Glioependymal cyst in the posterior fossa.
AB  - A large cyst filled with clear fluid was resected from the cerebellum of a 29
      year-old man. By light microscopy the cyst was lined by flat epithelial cells.
      These epithelial cells abutted on a glial layer and immunohistochemical staining
      revealed that some of them expressed glial fibrillary acidic protein. Corpora
      amylacea were noted within the glial layer. Ultrastructurally, 2 types of cells
      lining the cyst were identified. One was characterized by electron-dense
      cytoplasm, cytoplasmic vacuoles, microvilli without surface-coated material,
      cilia, and basal bodies. The other was a cell with a smooth cytoplasmic membrane,
      round nucleus, and clear cytoplasm. Zonulae adherentes was observed between cyst
      lining cells and the cyst lining cells were shown to rest directly on the glial
      layer. Surprisingly, myelinated axons were identified in the glial layer,
      although nerve cells were not identified. These findings are compatible with
      those of a glioependymal cyst. The origin of glioependymal cysts of the posterior
      fossa is not understood, but possibilities include neuroglial heterotopia,
      persistent Blake's pouch (diverticulum of the roof of fourth ventricle), and
      remnants of a tela chorioidea. The location of the cyst and the presence of
      myelinated axons in the cyst wall may be best explained by an origin from
      neuroglial heterotopia.

PMID- 9020390
TI  - Amyotrophic lateral sclerosis: occurrence of Bunina bodies in the locus ceruleus
      pigmented neurons.
AB  - Bunina bodies, which are small eosinophilic intracytoplasmic inclusions, have
      been considered to be specific for amyotrophic lateral sclerosis (ALS), a fatal
      neurodegenerative disease of unknown cause in adults. They are found usually in
      the remaining lower motor neurons. We encountered a 66-year-old woman with
      sporadic ALS showing Bunina body-like eosinophilic inclusions in the cytoplasm of
      some pigmented neurons in the otherwise intact locus ceruleus (LC).
      Ultrastructural examination of the LC confirmed that a few pigmented neurons
      actually contained inclusions identical to Bunina bodies. The finding indicates
      that Bunina bodies can occur in LC pigmented neurons and suggests that LC may
      also be involved in the disease process in ALS.

PMID- 9020389
TI  - Hemimegalencephaly--morphological and immunocytochemical study.
AB  - Hemimegalencephaly (HME), a rare congenital abnormality characterized by
      unilateral enlargement of the cerebral hemisphere, is one of the less common
      causes of intractable seizures. We report a 6-month-old infant with uncontrolled
      seizures who was diagnosed to have a large mass lesion based on a CT scan.
      Postmortem examination revealed left-sided HME with pachygyria, widened cortex,
      indistinct grey-white junction, and distorted deep nuclear masses. Histological
      features included loss of cortical lamination, large atypical neurons with
      argyrophilic accumulations, ballooned cells, neuronal heterotopia, and
      astrocytosis with dystrophic calcification. The heterotopic neurons in the white
      matter were present in a radial pattern suggestive of aberrant neuronal
      migration. Several large neurons were dystrophic with cytoskeletal abnormalities
      like phosphorylated high molecular weight neurofilament and ubiquitin in the
      cytoplasm. However, typical neurofibrillary tangles with Congo red and tau
      positivity were not observed. Synaptophysin labelling was found to be decreased
      in the cortex, but some of the abnormal neurons had dense perisomatic label. The
      majority of the balloon cells were astrocytic in origin, being positive for glial
      fibrillary acidic protein and negative for the neuronal markers. Although the
      etiology of HME is not known, it provides an opportunity to study anomalous
      development of the brain and neuronal developmental abnormalities.

PMID- 9020391
TI  - Cystic chondroma arising from the falx cerebri: a case study with review of
      literature.
AB  - A 28-year-old woman was presented with an 1-year history of headache, double
      vision and left hand and foot paresthesia. Clinical and CT findings were
      evaluated malignant. During the operation a solid mass attached to the falx
      cerebri was found. Pathological examination showed a chondroma with large central
      cystic degeneration. Our review of the literature revealed only 9 cases of
      falcine chondroma up to now, excluding ours.

PMID- 9020392
TI  - Pathologic assessment of cerebellar atrophy following acute lithium intoxication.
AB  - Lithium carbonate is a widely used pharmacologic agent for acute bipolar
      disorder, long term prophylaxis of mania in a bipolar patient, and prevention of
      "manic overshoot" with an antidepressant in acute depression in a bipolar
      patient. Although clinical neurological associations with lithium overdose have
      been-established, there has been a dearth of reports of pathologic changes
      related to lithium toxicity. We report a case of a 52-year-old Black female with
      bipolar disorder who had been treated with lithium for over 5 years and who
      expired 24 days after presenting in a stuporous state with an elevated lithium
      level of 3.2 mEq/l. Postmortem neuropathologic examination revealed severe
      cerebellar atrophy of the internal granule and Purkinje cell layers with
      attendant Bergmann gliosis presumably resulting from chronic lithium use and
      toxicity. There was also Alzheimer type II cell change in the thalamus and
      lentiform nuclei possibly due to terminal uremia. In summary, this is a unique
      case which appears to illustrate cerebellar atrophic changes related to lithium
      therapy and acute lithium intoxication.

PMID- 9020393
TI  - Mdr1 mRNA expression differs between grade III astrocytomas and glioblastomas.
AB  - 104 N2-frozen samples from 33 astrocytic tumors previously untreated with
      cytotoxic drugs have been analyzed for the expression of p-glycoprotein
      transcripts (mdrl) by RT-PCR using beta2-microglobulin as an internal control. A
      remarkable variation was observed even within a single tumor in 50% of the cases.
      Nevertheless, a difference became visible between the groups of anaplastic
      astrocytomas and glioblastomas. While 78% of the grade 3 astrocytomas contained
      at least a minimum of 1 sample with a very low mdr1 expression, this was the case
      only in 23% of the glioblastomas. This supports an earlier observation revealing
      a positive correlation between tumor grading and the tumor cell fraction stained
      with the monoclonal antibody JSB1. On the other hand, no major differences were
      found between the histological groups when the samples with the highest mdr1
      expression were selected to represent the individual tumors. Those samples are
      less informative. They might be derived from tumor regions in which capillaries
      deliver a larger fraction of the total mRNA pool. No induction of mdr1 was
      observed in some early astrocytoma or glioblastoma cell cultures even after
      administration of high concentrations of the drugs ACNU and VM26, often used in
      glioma therapy.

PMID- 9020394
TI  - Resistance of the hippocampus in Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) belongs to the group of subacute spongiform
      encephalopathies of animals and man. Their pathogenesis is certainly related to
      the formation and deposition in the brain of an amyloid-type specific protein,
      named PrPres (prion protein-resistant). The neuropathological topography of CJD
      does generally admit that archicortex is relatively spared, but only a few papers
      have been devoted to this issue. A neuropathological study of CJD cases divided
      in sporadic, familial, and iatrogenic forms of the disease has been carried out,
      taking into consideration the archipallial lesions in relation to different
      clinical and neuropathological parameters. The pyramidal cell layer of CA1 of all
      CJD cases did not show any major loss of neurons in comparison to that observed
      in other cortical fields of the limbic cortex (mainly in the presubicular and
      entorhinal cortex) and of the neocortex. Spongiogliotic reaction was observed
      only in the stratum radiatum and molecularis lacunosum in a iatrogenic case of
      the disease. The findings observed in the pyramidal cell layer of CA1 were
      neither related to the clinical duration of the disease nor to the severity of
      the lesions found in other limbic and neocortical areas. The results of this
      study support the view of no close relationships between the demential syndrome
      typically related to the clinical onset and progression of CJD, and the
      structural damage of the hippocampus classically involved in the pathogenetic
      mechanism of the amnestic syndrome related to the clinical presentation and
      course of more common forms of dementias, such as Alzheimer's disease.

PMID- 9020395
TI  - Pathologic correlations between ocular and cerebral lesions in 36 AIDS patients.
AB  - The eyes and brain have rarely been studied simultaneously in AIDS patients. We
      have examined both the eyes and brain of 36 patients autopsied these past 3
      years. Ten cases had concomitant involvement of eyes and brain by the same
      pathology: cryptococcus neoformans in 1, aspergillus in another, cytomegalovirus
      (CMV) infection in 5, and B cell lymphomas in 2 (1 patient had the last 2
      disorders associated). One patient presented pericapillary microhemorrhages in
      the retina of the left ocular globe as well as in the right occipital lobe. Six
      other patients had isolated CMV retinopathy and 4 others had B cell cerebral
      lymphomas. Eleven patients with foci of cerebral toxoplasmosis did not have
      visible cysts of toxoplasma gondii in their retina, in agreement with the other
      series devoted to the concomitant study of the eyes and brain in AIDS patients.
      On the other hand, their simultaneous involvement in an AIDS patient must first
      point to CMV infection.

PMID- 9020396
TI  - The mechanism of excretion of paraquat in rats.
AB  - Paraquat (PQ)(1,1'-dimethyl-4,4'-bipyridinium) is a toxic herbicidal cation. The
      renal excretory mechanisms of PQ and its interactions with organic cations and
      anions were investigated in anaesthetised rats. The renal clearance of PQ was
      studied in male Wistar rats using inulin as the marker of glomerular filtration
      rate. The fractional excretion of paraquat (FEpq) decreased from 2.1+/-0.01 to
      1.2+/-0.03 as the plasma concentration rose from 0.4+/-0.02 to 21.2+/-1.6 microM.
      These results demonstrated that the excretion of PQ was greater than glomerular
      filtration, concentration dependent and saturable, indicating that it was
      secreted by an active transport system. The excretion of PQ was dependent
      predominantly on the glomerular filtration rate with a small secretory component
      (Km = 8.5+/-3.1 microM, Vmax = 114+/-19 nmol/kg per min). The clearance of PQ was
      not inhibited by high doses of cimetidine, or p-aminohippurate. However, quinine
      (P = 0.001) and N-methylnicotinamide (NMN) (P = 0.03) reduced the FEpq,
      suggesting that they share a similar cation transport system with PQ. In summary,
      PQ is actively secreted by the rat kidney via a cation transport system.

PMID- 9020397
TI  - Contribution of oxygen radicals to DNA cleavage by quinone compounds derived from
      phenolic antioxidants, tert-butylhydroquinone and 2,5-di-tert-butylhydroquinone.
AB  - The effects of synthetic phenolic antioxidants, tert-butylhydroquinone (TBHQ),
      2,5-di-tert-butylhydroquinone (DTBHQ) and 3-tert-butyl-4-hydroxyanisole (BHA), on
      DNA cleavage were examined with supercoiled plasmid DNA, pUC18, in vitro.
      Extensive single and double strand breaks of DNA by TBHQ were observed and almost
      all the DNA was converted to the linear form at 10(-2) M. The cleavage was
      stimulated by both CuCl2 and FeCl2, though the effect of FeCl2 was smaller. Metal
      ion chelators and some oxygen radical scavengers inhibited the cleavage. The
      generation of TBHQ semiquinone radical and hydroxyl radical in the presence of
      copper was demonstrated by ESR spectroscopy. DTBHQ also caused DNA cleavage,
      though its effect was much smaller than that of TBHQ. BHA had no effect in the
      experimental systems employed. Oxygen radicals were considered to contribute to
      the DNA cleavage by TBHQ and DTBHQ.

PMID- 9020398
TI  - An ultrastructural evaluation of acute 1-nitronaphthalene induced hepatic and
      pulmonary toxicity in the rat.
AB  - 1-Nitronaphthalene is a mutagenic particulate of diesel exhaust which causes
      acute liver and lung toxicity in rodents. The studies presented here describe
      morphological changes in the lung and liver at several time intervals following a
      single injection of 1-nitronaphthalene (100 mg/kg, i.p.) in male Sprague-Dawley
      rats using transmission and scanning electron microscopy. Although both the lungs
      and liver are injured by 1-nitronaphthalene, the lungs appear to be the primary
      target organ. Within 4 h of treatment, all 1-nitronaphthalene treated animals
      exhibited respiratory distress characterized by labored breathing, severe gasping
      and chromodacryorrhea. The primary ultrastructural alteration were hydropic
      changes in the non-ciliated bronchiolar (Clara) cells of the distal-most
      bronchioles of the lung. These were apparent as early as 1 h after 1
      nitronaphthalene injection, while adjacent ciliated cells showed no alterations.
      Over a 24 h period, the bronchioles showed progressive ultrastructural changes
      leading to necrosis and exfoliation of both ciliated and Clara cells.
      Interstitial pneumonitis and edema were observed in all animals treated with 1
      nitronaphthalene, and was usually associated with bronchioles containing necrotic
      epithelium. In the liver, ultrastructural changes were observed in the
      centrilobular hepatocytes at 8 h and consisted of cytomegaly, loss of continuous
      inner membrane and reduced matrix density of the mitochondria. At 48 h, cellular
      damage to centrilobular hepatocytes was severe and nearly all mitochondria were
      damaged. Elevated levels of alanine aminotransferase, aspartate aminotransferase
      and bilirubin were detected in the serum of animals treated with 1
      nitronaphthalene at 8-48 h. In conclusion, 1-nitronaphthalene is a pulmonary
      toxicant with a unique progression of injury, which primarily damages Clara cells
      followed by ciliated cells. This disparity is likely due to a difference in the
      bioactivation of 1-nitronaphthalene. Furthermore, this systemic toxicant also has
      injurious effects on the centrilobular region of the liver which precedes lung
      injury.

PMID- 9020399
TI  - The biochemical studies on phalloidin-induced cholestasis in rats.
AB  - We investigated sequential changes in bile flow, serum and biliary biochemical
      parameters in phalloidin-induced cholestasis in rats. Intrahepatic cholestasis
      was induced by administration with phalloidin (500 microg/kg) for 7 days, and
      then the animals were allowed to survive for 1, 2, 4, 7, 14 and 28 days after the
      last treatment. In phalloidin-treated rats, bile flow significantly decreased up
      to 4 days of recovery, compared with the control animals. In contrast, serum ALP
      activity, LAP activity, cholesterol concentration and phospholipid concentration
      exhibited a marked elevation throughout the recovery periods. For biliary
      parameters, bilirubin excretion rate was unchanged but, cholesterol excretion
      rate showed a marked decrease throughout the recovery periods. These results
      demonstrate that some parameters, particularly important indexes of cholestasis
      (serum ALP, cholesterol, bile flow and so on), continued significant changes at
      least 4 days after the last administration of phalloidin. These results
      demonstrate that successive treatment with phalloidin can cause damage in most of
      serum and biliary parameters at a chronic stage of cholestasis. Thus, our
      findings may provide useful information for diagnosis of drug-induced cholestasis
      and help to further elucidate the biochemical mechanisms of drug-induced
      cholestasis in humans.

PMID- 9020400
TI  - Effects of X-irradiation on nerve growth factor in the developing mouse brain.
AB  - The involvement of neurotrophins after radiation injury during brain development
      were studied in pregnant mice (C 57/B1) exposed on gestation day 15 to X-ray
      doses of 0.02-2 Gy. Nerve growth factor protein (NGF) and different cholinergic
      markers were investigated on postnatal day 1 (P1) and day 21 (P21); in situ
      hybridization with brain-derived neurotrophic factor (BDNF) and trkC (receptor
      serving to bind neurotrophin-3) probes was investigated on P21 in cortex,
      hippocampus, septum and cerebellum. The level of NGF protein was increased in
      irradiated forebrain on P1 in a dose-related manner. However, on P21 the NGF
      protein dropped down below the control levels in irradiated hippocampus and
      cerebellum. The response of acetylcholine esterase (AChE) activity in cerebellum
      at P21 was correlated with the changes in the amount of NGF. The intensity of
      cell labelling with trkC probe decreased after irradiation in the region of the
      hippocampus at P21, especially in dentate gyrus. The expression of BDNF mRNA was
      increased at P21 by low doses of irradiation (0.02-1 Gy) but was decreased by a
      high dose (2 Gy) in the same area. Thus, the radiation induced an alteration of
      neurotrophins, and the changes varied depending on the dose or time after
      irradiation. Such alterations in the pattern of growth factor production may
      modulate the response of cells to radiation. Furthermore, NGF protein levels and
      the expression of BDNF and trkC mRNA were affected by radiation doses as low as
      0.02 Gy, indicating that during development the neurotrophins and their receptors
      are very sensitive to radiation.

PMID- 9020401
TI  - The inhibitory effect of the neuromuscular blocking agent, gallamine
      triethiodide, on camel retina acetylcholinesterase activity.
AB  - The present investigation addresses the mode of inhibition of the camel retinal
      acetylcholinesterase (AChE) activity by gallamine triethiodide, which is known to
      be a specific non-depolarizing neuromuscular blocking agent and polar cholinergic
      antagonist. This study gave the following results: it was found that gallamine
      (GA) reversibly inhibited the AChE activity in a concentration dependent manner,
      the IC50 being about 0.633 mM. The Km for the hydrolysis of acetylthiocholine
      iodide by AChE was found to be 0.0803 mM in the control system, and the value
      increased by 19-463% in the GA (0.125-1.0 mM) treated systems. The Vmax was 0.649
      micromol/min per mg protein for the control as well as GA treated systems. Dixon
      as well as Lineweaver-Burk plots and their secondary replots indicated that the
      nature of the inhibition is of the reversible competitive type. The Ki value was
      estimated as 0.160 mM. The Ki value increased with an increase in substrate
      concentration. The turnover number (Kcat) and specificity constant (Ksp) were
      62.1 min(-1) and 7.73 x 10(5) (M x min)(-1) in the control system while the value
      for one parameter (Ksp) was decreased by 25-83% in the GA (0.125-1.0 mM) treated
      systems.

PMID- 9020402
TI  - Acute exposure to ozone does not influence neuroreceptor density and sensitivity
      in guinea pig lung.
AB  - The effects of acute exposure of guinea pigs to 3 ppm of ozone for 2 h on the
      receptor density and sensitivity of the muscarinergic-, the histaminergic- and
      the beta-adrenergic receptor systems were studied, in order to provide more
      insight in the complex mechanisms underlying the well known ozone-induced changes
      in receptor functionality. The exposure to ozone did not change either the total
      amount of receptors present in lung tissue, nor the receptor sensitivity of the
      systems studied. Although no effects were observed, this does not yet fully
      exclude the receptor system for being a target of ozone exposure. The receptor
      function can be changed after exposure to ozone, e.g., the coupling with the G
      protein can be influenced. Furthermore, the G-protein itself may have been
      altered or changes can occur at lower levels in the receptor signal transmission
      route leading to functional changes after stimulation of the receptor with an
      agonist.

PMID- 9020403
TI  - Effect of ozone on metabolic activities of Escherichia coli K-12.
AB  - Escherichia coli K-12 cell suspensions in buffer were exposed to ozone at a
      concentration of 600 ppm. Measurements were made of cell viability,
      glyceraldehyde-3-phosphate dehydrogenase, malate dehydrogenase, lactate
      dehydrogenase, glutathione disulfide reductase, nonprotein sulfhydryl and total
      sulfhydryl compounds. Cell viability was not affected when E. coli K-12 was
      exposed to ozone for less than 10 minutes. The most sensitive parameter was
      glyceraldehyde-3-phosphate dehydrogenase followed by nonprotein sulfhydryl and
      total sulfhydryl compounds. Effects on malate dehydrogenase, lactate
      dehydrogenase and glutathione disulfide reductase were negligible. Cell survival
      and induction of lipid oxidation were also determined using two strains of E.
      coli K-12 (rec A, deficient in DNA repair and wild-type). The extent of membrane
      lipid oxidation correlated with cell viability in a dose-dependent manner and the
      survival curves of both strains showed similar sensitivity to ozone. The data
      suggest that the sulfhydryl group in the membrane is the primary target of ozone
      attack. Rec A DNA repair system does not appear to play a role in ozone
      resistance.

PMID- 9020404
TI  - Induction and decline of hepatic cytochromes P4501A1 and 1A2 in rats exposed to
      hyperoxia are not paralleled by changes in glutathione S-transferase-alpha.
AB  - We investigated the effects of hyperoxia on the activities of hepatic
      ethoxyresorufin O-deethylase (EROD) (CYP1A1), methoxyresorufin O-demethylase
      (MROD) (CYP1A2), and glutathione transferase-alpha (GST-alpha), and the status of
      protein thiols (PSH) in male Sprague-Dawley rats. Twenty-four h of hyperoxia more
      than doubled EROD and MROD activities, which were increased 7.6- and 3.3-fold,
      respectively, after 48 h of hyperoxia. The increases in EROD and MROD activities
      were paralleled by enhanced CYP1A1/1A2 apoproteins contents, as detected by
      Western analysis. At 60 h of hyperoxia, by which time hyperoxic Sprague-Dawley
      rats display marked respiratory distress, pulmonary edema, and other markers of
      pulmonary dysfunction, the activities and levels of hepatic CYP1A1 and 1A2 had
      declined dramatically and returned to levels observed in air-breathing control
      animals. Hepatic activities of GST-alpha, as well as PSH status, were not altered
      significantly in the hyperoxic animals at any time point. The marked induction
      and subsequent decline of hepatic CYP1A1/1A2 activities in rats exposed to
      hyperoxia suggest that these enzymes may contribute to the mechanisms of injury
      and/or to adaptive responses to hyperoxic exposures in vivo.

PMID- 9020405
TI  - Comparison of covalent binding of acetaminophen and the regioisomer 3'
      hydroxyacetanilide to mouse liver protein.
AB  - The hepatotoxicity of the analgesic acetaminophen has been previously attributed
      to metabolic activation by cytochrome P450 to the reactive intermediate N-acetyl
      p-benzoquinone imine. At therapeutic doses this species is detoxified by reaction
      with glutathione; however, following a hepatotoxic dose, liver glutathione levels
      are depleted and the metabolite covalently binds primarily to cysteine groups on
      proteins as 3-(cystein-S-yl)acetaminophen adducts. Altered function of critical
      proteins has been postulated to be the mechanism of hepatotoxicity. Covalent
      binding has been studied by both radiochemical methods and immunochemical
      methods. Utilizing Western blot analysis with an antiserum which recognizes
      acetaminophen we have previously shown that covalent binding occurs on a number
      of proteins in various hepatic fractions. In an effort to better understand the
      role of covalent binding in the toxicity, others have studied the non-hepatotoxic
      isomer 3'-hydroxyacetanilide. Administration of large doses of radiolabeled
      acetaminophen or 3'-hydroxyacetanilide resulted in similar levels of covalent
      binding to proteins. To better understand the role of covalent binding in
      toxicity we have administered mice 3'-hydroxyacetanilide and acetaminophen, and
      analyzed liver fractions for protein adducts using anti-3-(cystein-S
      yl)acetaminophen and anti-arylacetamide antisera in Western blot assays. Analysis
      of liver fractions from acetaminophen-treated mice, with both antisera showed, as
      has been previously reported, that acetaminophen covalently binds to a number of
      hepatic proteins. In liver from 3'-hydroxyacetanilide-treated mice, covalent
      adducts were detected with an anti-arylacetamide antiserum only. A major 3'
      hydroxyacetanilide protein adduct was observed in microsomes at 50 kDa. Minor
      adducts were observed at 47 kDa in microsomes and 56 kDa in cytosol. 3'
      Hydroxyacetanilide protein adducts were not observed in the 10,000 x g pellet.
      Densitometric analysis of a time course of 3'-hydroxyacetanilide protein adducts
      indicated that peak levels of the 50 kDa microsomal protein adduct occurred at 1
      h and subsequently decreased.

PMID- 9020406
TI  - The timing of immunization affects the development of diabetes in rodents.
AB  - BACKGROUND: Insulin-dependant diabetes mellitus (IDDM) is an autoimmune disease
      that can be altered by immune modulation. NOD mice and BB rats have been used as
      models of spontaneous IDDM. The development of diabetes in these animals has been
      altered by several different immune modulators using relatively high doses for
      the size of the animal. The effect of pharmaceutical doses of vaccines on the
      development of diabetes in these rodents has not been adequately studied.
      METHODS: I studied the effect of administering killed human vaccines using low
      concentrations and as few as 3 doses. RESULTS: Administration of human vaccines
      to diabetic prone newborn animals starting before 2 weeks of age prevented the
      development of diabetes while administration of the pertussis vaccine starting at
      8 weeks of life was associated with an increased incidence of diabetes.
      CONCLUSIONS: Animal studies have demonstrated the timing and content of human
      vaccines can affect the development of diabetes. Clinical trials of new human
      vaccines are not designed and generally not powered to detect an effect of
      immunization on the development of IDDM. These animal toxicology studies indicate
      that the effect of vaccines on human insulin dependent diabetes needs to be
      examined.

PMID- 9020407
TI  - Lymphocyte activation and cytokine production in autoimmune hemolytic anaemia
      (AIHA).
AB  - We studied 16 patients affected by autoimmune hemolytic anaemia (AIHA), both
      idiopathic and associated with other diseases (B and T lymphoma, B hepatitis,
      gastric carcinoma, systemic lupus erythematosus) or alpha-methyldopa therapy, in
      order to value T- and B-cell activation. We determined the count of T- and B-cell
      subsets in peripheral blood, the proliferative response of peripheral blood
      lymphocytes (PBL) to phytohemagglutinin (PHA) and to pokeweed mitogen (PWM), the
      percentage of CD25+ cells in culture and interleukin (IL)-1alpha, IL-2, IL-4,
      tumor necrosis factor (TNF)alpha and soluble IL-2 receptor (sIL-2R) levels in
      sera and in culture. Except for an increase in CD4+ and CD8+ T cell number in a
      case of AIHA associated with a T lymphoma and an increase in the percentage of
      CD5+ and PCA1+ B cells in two cases of AIHA associated with B lymphoma and with
      SLE, no further data showed a relationship with the disease possibly associated
      with AIHA, so both idiopathic and secondary AIHA cases were analyzed together.
      CD4+ T cells were reduced in number in 9 cases, while CD8+ T cells were reduced
      in 6 cases. The percentage of CD5+ B cells was increased in 5 cases. The
      percentage of PCA1+ cells was increased in all cases (mean +/- sd: 18 +/- 22 vs
      0,2 +/- 1 in controls). The average PBL proliferative response to PHA was reduced
      (S.I. 71 +/- 55 vs 138 +/- 45 in controls) as well as that to PWM (S.I. 27 +/- 21
      vs 75 +/- 24 in controls), despite IL-2 high levels, in all cases, in both sera
      (mean +/- sd: 648 +/- 351 pg/ml vs 16 +/- 4 pg/ml in controls) and culture
      supernatants (mean +/- sd: 1045 +/- 677 pg/ml vs 195 +/- 51 pg/ml in controls).
      In PHA stimulated cultures the percentage of CD25+ cells was reduced (mean +/-
      sd: 37 +/- 18 vs 63 +/- 14 in controls), sIL-2R levels were like controls in 7
      cases. In sera sIL-2R levels were increased in all cases (mean +/- sd: 1256 +/-
      465 U/ml vs 256 +/- 114 U/ml in controls), IL-1alpha was increased in all cases
      too, while IL-4 levels were increased only in 7 cases. Linear regression analysis
      generally showed a low relationship between S.I. and IL-2, IL-4 and sIL-2R levels
      in supernatants of PHA stimulated culture as well as between S.I. and the
      percentage of CD25+ cells. Taken together these data suggest a state of B- and T
      cell hyperactivation in AIHA. The low PBL proliferative response in vitro,
      explained in previous studies as a temporary functional exhaustion, might be
      itself a sign of the complete lymphocyte activation occurring in vivo in AIHA.

PMID- 9020408
TI  - Oral administration of type I interferon modulates the course of experimental
      allergic neuritis.
AB  - We investigated the effect of oral administration of type I interferon (IFN) in
      experimental allergic neuritis (EAN) in Lewis rats immunized with bovine
      peripheral nerve myelin. Starting at 7 days preceding immunization, rats were fed
      daily until sacrifice either with 5000 U rat IFN-alpha/beta or mock-IFN. The
      clinical severity of EAN was significantly reduced in IFN-alpha/beta fed animals
      compared to mock-IFN fed controls. Demyelination, but not inflammation, was
      decreased in IFN-alpha/beta fed compared to mock-IFN fed rats at day 20 after
      immunization. In situ IFN-gamma production and inflammation were reduced when
      evaluated by immunocytochemistry at day 13 after immunization. Spleen cells from
      IFN-alpha/beta fed compared to mock-IFN fed EAN rats showed significantly reduced
      proliferation to stimulation with Con A or peripheral nerve myelin. IFN-gamma
      production in draining lymph node cells was significantly reduced after
      stimulation with bovine peripheral nerve myelin. Our data suggest that oral
      administration of IFN-alpha/beta reduces the severity of EAN, possibly by a
      reduction in IFN-gamma production.

PMID- 9020409
TI  - A novel anti-microfilament antibody, anti-135 kD, is associated with Raynaud's
      disease, undifferentiated connective tissue disease and systemic autoimmune
      diseases.
AB  - We report herein the characterization of a human IgG antibody reactive with a
      nonmuscle 135 kD microfilament-associated protein, anti-135 kD. Using nonmuscle
      epithelial PtK2 cells as substrate in indirect immunofluorescence, we identified
      a distinctive pattern of reactivity with microfilaments in sera from 12 of 165
      (7.3%) patients investigated for systemic autoimmune diseases and in only 2 of
      171 (1.2%) normal and rheumatic disease controls (P < 0.006, 95% Cl 1.46 to
      30.1). An association between anti-135 kD and Raynaud's phenomenon (n = 12/14,
      85.7%) with or without an associated systemic autoimmune disease was noted. The
      anti-135 kD specificity was established by several criteria. (1) The fluorescence
      was periodically distributed along microfilaments and concentrated at focal
      adhesions for all sera (n = 14). (2) On immunoblots, the 14 sera reacted with a
      PtK2 polypeptide of 135 kD. (3) IgG purified by blot-affinity from the 135 kD
      band (alpha-135) reproduced the fluorescent pattern of the original sera while
      IgG purified from other bands did not. (4) Double immunofluorescence with alpha
      135 and anti-alpha-actinin mAb indicated absence of antibody fluorescence at
      ruffling membranes where a-actinin was distributed. (5) IgG subclass analysis of
      anti-135 kD revealed that 12 (85.7%) sera are of IgG3 isotype and 2 (14.3%) are
      of IgG1 isotype while the light chain expression was kappa restricted. This is
      the first report of an antibody to a 135 kD microfilament protein. Anti-135 kD
      expand the repertoire of anti-microfilament and anticytoskeletal antibodies in
      human sera.

PMID- 9020410
TI  - In vivo migration of tonsil lymphocytes in rheumatoid synovial tissue engrafted
      in SCID mice: involvement of LFA-1.
AB  - Integrin-adressin binding is a critical step in lymphocte attachment to target
      tissues. The mucosal recognition systems (alpha E beta 7, alpha 4 beta 7, MADcam
      1) have been implicated in the autoimmune process in rheumatoid arthritis. We
      developed a model for in vivo study of radio-labelled lymphocyte circulation and
      their attachment to human rheumatoid synovium. We studied the homing of tonsil
      lymphocytes, considered as mucosal lymphocytes, and the involvement of alpha E
      beta 7 integrin and LFA1 in the homing of tonsil lymphocytes. We engrafted human
      rheumatoid synovium subcutaneously in 6 week old SCID CB17 mice. Three weeks
      later, we injected intraperitoneally 20 IO6 human peripheral blood or tonsil
      mononuclear cells, previously labelled with 3 mCFi HMPAO-99mTc. A mouse total
      body scintigram was obtained 20 h postinjection. The same protocol was performed
      after treatment of the MNC and mAb against LFA-1 (CD11a) or alpha E beta 7
      (CD103). Tonsil MNC retention in the rheumatoid synovial graft 20 h post
      injection was enhanced compared to blood MNC (12731 +/- 8297cpm/200 pixel) versus
      5982 +/- 4713cpm/200 pixel, p < 0.05). A monoclonal antibody against LFA 1
      decreased the activity in the graft (4152 +/- 1287 cpm/200 pixel), p < 0.05. No
      significant difference in tonsil MNC attachment to rheumatoid synovial tissue was
      observed with a mAb against alpha E beta 7 (8057 +/- 5009 cpm/200 pixel). Our
      results showed an increase in radiolabelled mucosal MNC migration in synovial
      tissue engrafted in SCID mice compared with blood MNC. Moreover, the date suggest
      that LFA-1 but not the alpha E beta 7 integrin is involved in tonsil MNC binding
      to synovial tissue in RA.

PMID- 9020411
TI  - Fusidic acid and insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a major cause of morbidity and
      mortality from long-standing complications. The autoimmune nature of IDDM has
      encouraged use of immunosuppressive and antiinflammatory strategies to better
      preserve residual pancreatic beta-cell function at the time of diagnosis. Fusidic
      acid and its sodium salt, fusidin, is a relatively atoxic antibiotic used mainly
      in the treatment of staphylococcal infections. Recently, fusidin has been
      demonstrated to possess immunosuppressive functions in vitro and in vivo, and the
      drug has shown promise in preventing the disease in animal models of IDDM and in
      a preliminary trial in IDDM patients.

PMID- 9020412
TI  - Asthma: from childhood to adulthood.

PMID- 9020413
TI  - Sodium cromoglycate as a replacement for inhaled corticosteroids in mild-to
      moderate childhood asthma.
AB  - We investigated whether sodium cromoglycate 10 mg three times daily, delivered as
      an aerosol via Nebuhaler (in addition to terbutaline 0.5 mg three times daily),
      could replace inhaled steroid in children with mild-to-moderate asthma. Children
      (mean age 10.3 years) were randomly allocated to 12-week treatment with sodium
      cromoglycate 10 mg plus terbutaline 0.5 mg (group A; n = 30) or placebo plus
      terbutaline 0.5 mg (group B; n = 32), both taken three times a day. The daily
      steroid dose was reduced by 50 microg/week for 4 weeks from a starting dose of
      200 microg. Fewer patients withdrew owing to worsening asthma from group A (n =
      1) than group B (n = 11). Symptom scores, morning and evening peak flows, and
      additional beta2-agonist usage, recorded on diary cards, were better in group A
      than group B. Lung function measured at clinic visits was unchanged in either
      group. Overall opinions of efficacy favoured Group A. Adverse events were similar
      in the groups. Sodium cromoglycate plus terbutaline substituted effectively for
      inhaled steroid therapy.

PMID- 9020414
TI  - Does benzyl benzoate prevent colonization of new mattresses by mites? A
      prospective study.
AB  - In 12 house-dust-mite-infested double beds, one of the mattresses was replaced by
      a new one, the other being regarded as a mite source. All new mattresses were
      treated in a double-blind fashion, with either benzyl benzoate or placebo before
      being placed on the bed as well as 1 year later. They were examined for mites and
      allergen concentrations over a period of 18 months. This period of time covered
      two mite seasons. Dust samples were taken bimonthly and analyzed by guanine test
      strip, microscopic mite counting, and determination of the mite allergens Der p 1
      (Dermatophagoides pteronyssinus) and Der f 1 (D. farinae) by ELISA. Although, at
      the end of the observation period, the new mattresses still had significantly
      lower mite and allergen levels than the old mattresses, there were no significant
      differences between the placebo and the benzyl benzoate groups. In our setting,
      benzyl benzoate plus frequent cleansing was not significantly more effective in
      controlling mites than frequent cleansing alone.

PMID- 9020415
TI  - Effect of local allergen priming on early, late, delayed-phase, and epicutaneous
      skin reactions.
AB  - Allergic disease is reflected in a chronic inflammatory response to an allergen.
      It is thought that local allergen priming underlies this chronicity. To assess
      the effect of allergen priming on the amplitude and histologic effect of the
      allergic reaction, four sequential, intracutaneous skin tests were done with 48-h
      intervals in 13 patients allergic to the house-dust mite Dermatophagoides
      pteronyssinus (Dpt). Reactions were measured at 15 min, and at 6, 24, and 48 h.
      Subsequently, epicutaneous tests were done on Dpt-primed spots (n = 5). At 6, 24,
      and 48 h, reactions increased after priming (P < 0.006), with unaltered early
      reactions. Epicutaneous reactions to Dpt on primed spots were larger than in
      epicutaneous controls on similarly primed skin. Local intradermal priming results
      in greater inflammatory responses at both intra- and epicutaneous challenge. This
      mechanism may explain the chronicity of allergic reactions at epithelial
      surfaces.

PMID- 9020416
TI  - Allergenicity of acid protease secreted by Candida albicans.
AB  - We have previously reported the cases of Candida albicans (C. alb) acid protease
      (CAAP)-induced atopic asthma. In this study, the allergenicity of the released
      enzyme CAAP was examined among asthmatic patients with positive immediate skin
      response to crude C. alb antigen. Among 49 patients with positive skin response
      to crude C. alb, anti-crude C. alb IgE antibodies were detected in 40 and anti
      CAAP IgE antibodies were detected in 18. Moreover, anticrude C. alb IgE
      antibodies were detected in all of the patients in whom anti-CAAP IgE antibodies
      were detected. No correlations between IgG antibodies to both antigens or between
      IgE and IgG antibodies to CAAP were observed. CAAP induced significant T-cell
      proliferation in 20/28 patients showing positive T-cell proliferation response to
      crude C. alb antigen. Most of the patients showing positive conjunctival response
      to crude C. alb antigen also showed positive response to CAAP. Most of the
      patients showing high levels of serum IgE antibody and positive histamine-release
      response of peripheral blood leukocytes to CAAP showed positive conjunctival
      response. The results indicate that CAAP is an important allergen in C. alb
      related mucosal allergy.

PMID- 9020417
TI  - Sedation in allergic rhinitis is caused by the condition and not by antihistamine
      treatment.
AB  - Sedation is regarded as a common side-effect of most H1-antihistamines. This view
      must be accepted, yet can hardly be assessed under treatment of allergic
      disorders. Since central sedative potency is hard to evaluate, different methods
      of measurement have been introduced in the four phases of clinical investigation.
      While tests of high complexity in early trials can detect true central effects,
      they seem to have the disadvantage of not taking into consideration the important
      interactions of drugs with the disorder. Therefore, we used a visual analog scale
      (VAS) as an instrument to demonstrate sedative effects in five clinical studies
      carried out between 1989 and 1994 with a total number of 1070 patients. Thereby,
      we could assess the result of the different components of the central
      interaction. In 1989, in a double-blind, placebo-controlled trial, we could show
      that the vigilance of patients suffering from seasonal allergic rhinitis
      increased significantly more under treatment with an antihistamine (mizolastine)
      than under placebo. From 1992 until 1994, we compared azelastine nasal spray
      either by the double-dummy technique with oral antihistamines (cetirizine,
      loratadine, and astemizole) or by the double-dummy or placebo-controlled design
      with monotherapy or combined therapy with azelastine tablets. A marked or
      statistically significant improvement of vigilance was found for all compounds
      (loratadine: P < 0.0001; cetirizine: P < 0.0254; and azelastine nasal spray: P <
      0.1409 to P < 0.0001). Even when taking azelastine as oral application, patients,
      in spite of the warning, reported a similar increase in vigilance (P < 0.2628 to
      P < 0.0001). Finally, we assessed the range of physiologic vigilance using the
      same VAS in healthy volunteers. In conclusion, we could prove that in all trials
      the baseline values of vigilance of untreated symptomatic patients were far below
      physiologic condition and improved under treatment to the upper range of healthy
      persons. Therefore, any sedative properties of modern H1-antihistamines should
      not limit their therapeutic use, since the truly threatening sedation results
      from the disorder itself.

PMID- 9020418
TI  - Comparisons of IgE, IgG, and IgG4 responsiveness to Dermatophagoides farinae in
      children by immunoblotting.
AB  - Although asthmatic children are often sensitized to the house-dust mite (HDM)
      during early childhood, it is not clear what antigenic components are associated
      with the early immune response of these children. To investigate this problem, we
      evaluated IgE, IgG, and IgG4 antibody responses to Dermatophagoides farinae (Df)
      by immunoblotting among three groups of children: group I aged 0-4 years, group
      II aged 5-9 years, and group III aged 10-14 years. In the group I subjects,
      positive IgE-binding reactions to 15- and 25-kDa components were found in 76% and
      44% of sera, respectively. Those to other components were generally low in
      frequency. In contrast, positive IgG-binding reactions to 15- and 25-kDa
      components were found in 44% and 24% of sera, and those to 30- and 110-kDa
      components in 48% and 88% of sera, respectively. Positive IgG4 reactions to 15-
      and 25-kDa components were found in 48% and 24%, respectively, and those to other
      components were very low. Positive IgE-binding reactions to these components
      gradually became more frequent with increasing age in groups II and III, while
      IgG and IgG4 reactivities were not markedly different in these age groups. These
      results suggest that the 15- and 25-kDa proteins of Df are important antigens
      associated with the initial IgE response to HDM in early childhood, while the 30-
      and 110-kDa proteins are associated with IgG and 15-kDa components with IgG4.

PMID- 9020419
TI  - Occupational rhinitis and bronchial asthma due to morphine: evidence from
      inhalational and nasal challenges.
AB  - A case of occupational bronchial asthma due to morphine in a nonatopic 46-year
      old woman is presented. The following diagnostic tests were used: a workplace
      trial with bronchodilator and placebo, and single-blind, placebo-controlled nasal
      and bronchial challenge with 0.5% morphine HCl. For the nasal challenge, four
      asthmatic patients were selected as a control group. The nasal washings were done
      before and 30 min, 3 h, 24 h, and 48 h after all challenges. In the nasal lavage
      fluid, the total numbers of eosinophils, neutrophils, basophils, and mast cells
      were counted, and, after the nasal challenge, total protein and albumin levels
      were measured. During the workplace trial, the PEF variability ratio increased
      from 5% to 38%. After the challenges, a decrease in the spirometric parameters
      (VC and FEV1) of about 30-40% was observed, with minimums at 24 and 48 h. An
      influx of granulocytes with an increase in the relative number of eosinophils and
      basophils from 3 h until 48 h after the challenge was observed in the nasal
      lavage fluid. The protein level in the nasal lavage fluid increased from 190 to
      1275 microg/ml 24 h after the challenge with an increase of relative albumin
      level from 24% to 40% at 24 h. In the control group, no changes in relative
      number of basophils and eosinophils and albumin/total protein ratio in the nasal
      lavage fluid or in the spirometric parameters were observed after the challenge.

PMID- 9020420
TI  - Oral allergy syndrome (OAS) in pollinosis patients after eating pistachio nuts:
      two cases with two different patterns of onset.
AB  - We describe two uncommon cases of oral allergy syndrome (OAS) after eating
      pistachio nuts (p.n.) in subjects (a 54-year-old man and a 3-year-old girl) with
      exclusive skin prick test (SPT) positivity to Parietaria (P.) and pistachio nut
      (p.n.) allergens. Serologic P.- and p.n.-specific IgE determinations were also
      carried out. A double-blind, placebo-controlled food challenge (DBPCFC) was
      performed, for ethical reasons, only in the adult patient, but we observed a
      positive intraoral reaction only after slight scratching of the oral mucosa.
      Since this patient had put three whole p.n. with their shells into his mouth,
      breaking them with his teeth, before the onset of symptoms, we suggest that
      slight injury of the oral mucosa may enhance the local response. Preliminary
      results with SDS-PAGE and immunoblotting demonstrate the occurrence of a slight
      degree of cross-reactivity between these allergens, but further studies are
      necessary to obtain a definite conclusion.

PMID- 9020421
TI  - An electrical impedance technique for assessment of wheals.
AB  - In previous studies of the electrical impedance of the skin, we introduced a set
      of physical indices which could be used to distinguish between the cutaneous
      effects produced by different irritants and allergic contact reactions. In this
      study, wheals were induced in 10 allergic patients by performing prick tests on
      the forearm with the relevant allergen and histamine, respectively. Normal skin
      was used for control. The wheals were evaluated by visual scoring, laser Doppler,
      and electrical impedance. As expected, there was a close agreement between the
      visual and laser Doppler readings. Compared to the controls, there were
      significant changes in the electrical impedance of the wheals, especially in the
      index related to the phase angle. The changes in the indices were found to follow
      a particular pattern, which diverged from those obtained in contact skin
      reactions of both allergic and irritant type. Our results indicate that, by the
      application of the impedance technique, it will be possible to characterize
      objectively and quantify the wheal reaction. The results also suggest that
      cutaneous reactions of completely different causes, such as allergic skin
      reactions of the late and immediate type, and irritant contact reactions, may be
      distinguished on the basis of their effects on the electrical impedance of the
      skin.

PMID- 9020422
TI  - Allergy to foods in patients monosensitized to Artemisia pollen.
AB  - It is known that patients with pollinosis may display clinical characteristics
      caused by allergy to certain fruits and vegetables, but subjects allergic to
      Artemisia seem to show particularly peculiar characteristics. The clinical
      features of 84 patients with rhinitis, asthma, urticaria, and/or anaphylaxis
      whose inhalant allergy was exclusively to Artemisia vulgaris were studied and
      compared with a control group of 50 patients monosensitized to grass pollen. The
      mean age for the beginning of symptoms was 30.2 years, and this was higher than
      in the control group (P < 0.05). We found the main incidence to be in women
      (70.2%). Some 42.3% had family history of atopia, lower than in the control group
      (P < 0.05), while the prevalence of asthma and urticaria was significantly higher
      (P < 0.05). Food hypersensitivity was reported by 23 patients (27.3%) allergic to
      Artemisia. The foods responsible (with respective numbers of cases) were honey
      (14), sunflower seeds (11), camomile (four), pistachio (three), hazelnut (two),
      lettuce (two), pollen (two), beer (two), almond (one), peanut (one), other nuts
      (one), carrot (one), and apple (one). None of the patients monosensitized to
      grass had food allergy. CAP inhibition experiments were carried out on a single
      patient. Results showed the existence of common antigenic epitopes in pistachio
      and Artemisia pollen for this patient. We concluded that mugwort hay fever can be
      associated with the Compositae family of foods, but that it is not normally
      associated with other foods.

PMID- 9020423
TI  - Nasal cytology in rhinitis children: comparison between brushing and blowing the
      nose.
AB  - Allergic rhinitis is a common disease in childhood, but nasal cytology is rarely
      used by pediatricians. We compared two techniques of cell sampling, brushing and
      blowing the nose, among 77 children suffering from chronic rhinitis, of whom 59
      were allergic. Staining by the May-Grunwald-Giemsa method enabled the evaluation
      of the density of cells and especially differential counting of the inflammatory
      cells. Staining by the Luna method was used as a control for the eosinophils. For
      the eosinophil count, we found a strong correlation between the two methods of
      collecting the nasal secretions (r = 0.96). Because blowing the nose is painless
      and easy to perform, it is more appropriate than brushing in routine use for the
      diagnosis of allergic rhinitis in children and in nasal challenge with allergens.

PMID- 9020424
TI  - Ultrastructural changes in the duodenal mucosa induced by ingested histamine in
      patients with chronic urticaria.
AB  - Histamine in food may be responsible for some cases of food intolerance. We
      previously demonstrated disturbances in the metabolism of ingested histamine in
      patients with chronic urticaria (CU) and proposed that this could be related to
      increased intestinal permeability to histamine. The present study was undertaken
      to look for ultrastructural changes in the intestinal tract that might explain
      this abnormality. We examined duodenal biopsies from seven patients with CU
      before and after intraduodenal administration of histamine (120 mg). Five
      subjects had clinical symptoms (diarrhea, urticaria, headache, accelerated heart
      rate, and drop in blood pressure) within 1 h of duodenal histamine challenge
      (DHC). Ultrastructural changes, including edema of the interstitial tissue,
      enlargement of the basal intercellular spaces, slight congestion of the
      endothelial cells, and pericapillary edema, were observed in six subjects 45 min
      after DHC. In all the biopsies, the epithelium was normal, and the tight
      junctions were not modified by DHC. This morphologic study demonstrates that
      histamine can induce edema in the basal intercellular spaces of the duodenal
      mucosa and in the submucosa without evident change in the integrity of
      intercellular junctions. The most plausible route for histamine to have taken
      would appear to be an intracellular one.

PMID- 9020425
TI  - Evaluation of recombinant allergens Bet v 1 and Bet v 2 (profilin) by Pharmacia
      CAP system in patients with pollen-related allergy to birch and apple.
AB  - Sixty-five patients presenting either rhinoconjunctivitis or asthma and
      sensitized to pollens of trees of the order Fagales were studied by the Pharmacia
      CAP system in order to assess specific IgE for the important birch pollen
      allergens Bet v 1 and Bet v 2. All 65 subjects reacted to at least one of the
      recombinant birch allergens: 43% to Bet v 1, 30.7% to Bet v 2, and 26% to both.
      Patients monosensitized to birch did not react to Bet v 2. Of patients with a
      history of oral allergy syndrome after eating apples, 16/28 (57%) reacted to Bet
      v 1; among 20 polysensitized subjects presenting oral allergy syndrome after
      consumption of apple, four reacted to Bet v 2 (20%). Among patients with IgE
      against both recombinant allergens, six (35.30%) presented symptoms of allergy
      after eating apples. Our results indicate that sensitization to Bet v 1 is
      specific for birch and apple allergies, whereas sensitization to Bet v 2 is
      common in polysensitized patients.

PMID- 9020426
TI  - Antiallergic activity of topical lodoxamide on in vivo and in vitro models.
AB  - Lodoxamide is an antiallergic drug acting as a mast-cell stabilizer, which is
      effective in the treatment of allergic conjunctivitis. The study aimed to
      evaluate the effect of lodoxamide eye-drops on the inflammatory early-phase
      reaction (EPR) changes induced by allergen-specific conjunctival challenge
      (ASCC). This was a cross-over, double-blind, placebo-controlled, randomized
      study, including 10 outpatients suffering from allergic rhinoconjunctivitis due
      to Parietaria judaica. Patients received one drop of lodoxamide tromethamine 0.1%
      or placebo 30 min before each ASCC. Clinical evaluation and cytologic assessment
      were done at baseline and 30 min after each ASCC. Lodoxamide induced a reduction
      in total symptom score and hyperemia during the EPR (P < 0.05). Lacrimation,
      itching/burning, and eyelid swelling were only slightly (nonsignificantly)
      reduced. Lodoxamide induced a reduction in the total number of inflammatory cells
      and neutrophils during the EPR (P < 0.02). Eosinophil and lymphocyte number and
      ICAM-1 expression showed only a slight, not statistically significant decrease.
      Placebo did not affect the studied parameters. Lodoxamide reduced early clinical
      events and cellular changes after ASCC consistently with its activity as mast
      cell stabilizer. Moreover, lodoxamide was able to downregulate in vitro ICAM-1
      expression on the continuously cultured, differentiated conjunctival cell line
      WK. This was shown both in basal conditions (P < 0.05) and upon interferon-gamma
      stimulation (P < 0.03), although at high concentration.

PMID- 9020427
TI  - Sesame seed and sesame seed oil contain masked allergens of growing importance.
AB  - Sesame seed and sesame seed oil have been thought of as rare causes of food
      allergy, representing less than 1% of all food allergy cases. We now report nine
      cases of IgE-dependent allergy to sesame seed and/or sesame seed oil, six of
      which were diagnosed in 1995 alone. Our skin test results draw attention to the
      poor quality of a commercial sesame seed extract and the good sensitivity of skin
      prick tests made with a freshly prepared sesame seed flour extract. The diagnosis
      of this food allergy was established by double-blind oral provocation tests, with
      doses of sesame seed flour ranging from 100 mg to 10 g. Allergy to sesame seed
      oil was also demonstrated in some cases. The sensitivity of the Pharmacia
      Phadebas CAP System for the detection of sesame seed-specific IgE was only
      mediocre. We draw attention to the important use of sesame seed in modern
      cooking, a fact which may explain the growing frequency of this allergy. We
      underline the particular risk with sesame seed oil. Sesame seed should also be
      considered a cause of allergic reactions to drug products and cosmetics.

PMID- 9020428
TI  - Cheese workers' lung.

PMID- 9020429
TI  - Occupational asthma in a cheese worker.

PMID- 9020430
TI  - Selective immediate allergic response to penicillin V.

PMID- 9020431
TI  - Intradermal testing of fixed drug eruption.

PMID- 9020432
TI  - Copro-eosinophil cationic protein (ECP) in food allergy.

PMID- 9020433
TI  - Trauma and orthopaedic surgeons.

PMID- 9020434
TI  - Trauma management in the United Kingdom.

PMID- 9020435
TI  - Recurrent rotational deformity of the femur after static locking of
      intramedullary nails: case reports.
AB  - Rotational deformity following intramedullary nailing may cause symptoms and
      require surgical correction by osteotomy. Reamed, locked intramedullary nailing
      may be performed, but concern about cortical blood supply and potential pulmonary
      dysfunction from reaming have led many surgeons to limit this and use smaller
      diameter nails. Slotted nails are commonly used but are less stiff in torsion
      than the newer unslotted nails, particularly at the lower diameters. We report
      two cases of recurrent femoral rotational deformity after using statically
      interlocked slotted intramedullary nails to correct existing femoral rotational
      deformities. These patients show that small diameter statically interlocked
      femoral nails with diminished bone-nail contact must be stiff enough in rotation
      to avoid potential recurrence.

PMID- 9020436
TI  - Clinical implications of stiffness and strength changes in fracture healing.
AB  - In the assessment of fracture healing by monitoring stiffness with vibrational
      analysis or instrumented external fixators, it has been assumed that there is a
      workable correlation between stiffness and strength. We used four-point bending
      tests to study time-related changes in stiffness and strength in healing tibial
      fractures in sheep. We aimed to test the validity of the measurement of stiffness
      to assess fracture strength. At each duration of healing examined, we found
      marked variations in stiffness and strength. Stiffness was shown to be load
      dependent: measurements at higher loads reflected ultimate strength more
      accurately. There was a biphasic relationship between stiffness and strength: at
      first there was a strong correlation regardless of loading conditions, but in the
      second phase, which included the period of 'clinical healing', stiffness and
      strength were not significantly correlated. We conclude that the monitoring of
      stiffness is useful primarily in assessing progress towards union but is
      inherently limited as an assessment of strength at the time of clinical union.
      Any interpretation of stiffness must take into account the load conditions.

PMID- 9020437
TI  - Patellectomy with vastus medialis obliquus advancement for comminuted patellar
      fractures: a prospective randomised trial.
AB  - We have compared the results of simple patellectomy (group A, n = 16) and
      patellectomy with advancement of the vastus medialis obliquus (group B, n = 12)
      in a prospective, randomised trial, with a minimum follow-up of three years. The
      results in group B were significantly better (p < 0.001) than those in group A.
      Although the patella should be preserved if possible, we advocate advancement of
      the vastus medialis obliquus when patellectomy is necessary.

PMID- 9020438
TI  - Fractures of the coracoid process.
AB  - We reviewed 67 consecutive patients with fractures of the coracoid process,
      classifying them by the relationship between the fracture site and the
      coracoclavicular ligament. The 53 type-I fractures were behind the attachment of
      this ligament, and the 11 type-II fractures were anterior to it. The relationship
      of three fractures was uncertain. Type-I fractures were associated with a wide
      variety of shoulder injuries and consequent dissociation between the scapula and
      the clavicle. Treatment was usually by open reduction and fixation for type-I
      fractures and conservative methods for type-II. At follow-up of the 45 available
      patients, 87% had excellent results, with no significant differences between the
      operative and non-operative groups or between the type-I and type-II fractures.
      We consider that operative treatment should be reserved for patients with
      multiple shoulder injuries with severe disruption of the scapuloclavicular
      connection.

PMID- 9020439
TI  - Aneurysmal bone cysts treated by curettage, cryotherapy and bone grafting.
AB  - We treated 26 patients with 27 aneurysmal bone cysts by curettage and cryotherapy
      and evaluated local tumour control, complications and functional outcome. The
      mean follow-up time was 47 months (19 to 154). There was local recurrence in one
      patient. Two patients developed deep wound infections and one had a postoperative
      fracture. We compared our results with previous reports in which several
      different methods of treatment had been used and concluded that curettage with
      adjuvant cryotherapy had similar results to those of marginal resection, and that
      no major bony reconstruction was required. We recommend the use of cryotherapy as
      an adjuvant to the surgical treatment of aneurysmal bone cysts. It provides local
      tumour control. Combination with bone grafting achieved consolidation of the
      lesion in all our patients.

PMID- 9020440
TI  - Radiological and clinical recurrence of giant-cell tumour of bone after the use
      of cement.
AB  - We have reviewed 13 operations on 11 patients using curettage and
      polymethylmethacrylate cement for giant-cell tumour of bone (GCT) to assess the
      value of radiology in the early detection of recurrence. There were four
      recurrences, the most specific radiological sign on plain radiography was lysis
      of 5 mm or more at the cement-bone interface. This preceded clinical signs by a
      mean of four months and was identified at a mean of 3.75 months after operation.
      There was not always a complete sclerotic margin around the cement, but when it
      was present, there was never evidence of recurrence. MRI was helpful in assessing
      cases with evidence of recurrence. Frequent surveillance with plain radiography
      should continue for one year after operation irrespective of clinical signs of
      recurrence. When the appearance of the plain radiographs suggests recurrence, MRI
      should be performed and followed by image-guided needle biopsy.

PMID- 9020441
TI  - One-stage revision surgery for infected megaprostheses.
AB  - We have reviewed the results of one-stage revision surgery in 18 patients for
      infection of megaprostheses implanted after the resection of malignant bone and
      soft-tissue tumours. At a mean follow-up of 52.0 +/- 35.0 months (18 to 135)
      infection was eliminated in 14 of the 18 patients. The infection-free patients
      showed no abnormal tests for inflammation and had a mean Enneking score of 20.6
      +/- 5.0 points (maximum 30 points). We suggest that one-stage revision without
      exchange of the anchorage parts is justified in patients with megaprostheses
      infected by antibiotic-sensitive micro-organisms.

PMID- 9020442
TI  - Free vascularised fibular grafting for reconstruction after tumour resection.
AB  - We have reviewed 30 patients at a mean of 36 months after free vascularised
      fibular transfer to reconstruct massive skeletal defects after resection of
      primary bone tumours. There were 23 malignant and 7 benign neoplasms, half in the
      lower limb and half in the upper. Arthrodesis was performed in 15 and intercalary
      bone replacement in 15. The mean fibular graft length was 189 mm. Union was
      achieved in 27 (90%) at an average of 7.6 months, and the 3-year survival was
      89%. There was a high complication rate (50%), but most resolved without greatly
      influencing the final outcome. There was local recurrence in two (6.7%), but 16
      of the 24 assessed patients (67%) had satisfactory functional results. This is a
      reasonably effective means of reconstruction for limb salvage after resection of
      tumours.

PMID- 9020444
TI  - The short form-36 health survey questionnaire in spine surgery.
AB  - The Short Form-36 (SF-36) health questionnaire has been put forward as a general
      measure of outcome in health care and has been evaluated in several recent
      studies in the UK. We report its use in three groups of patients after spinal
      operations and have compared it with the Oswestry and Low Back Pain disability
      scales. There was a significant correlation between all variables of the SF-36
      and the low-back scores. The mental-health items had the weakest correlation. Our
      study shows that the SF-36 questionnaire is valid and has internal consistency
      when applied to these patients.

PMID- 9020443
TI  - Free vascularised fibular strut graft for anterior spinal fusion.
AB  - A vascularised fibular strut graft was used for anterior spinal fusion in 16
      patients with spinal kyphosis. The procedure was abandoned in three because of
      difficulty in establishing a vascular anastomosis and in one because the grafted
      fibula dislodged two days after operation. One patient died after five days. Of
      the 11 remaining patients, there were seven males and four females. Their ages at
      the time of operation averaged 30.9 years (12 to 71). The number of vertebrae
      fused averaged 6.7 (5 to 9) and the length of fibula grafted averaged 10.9 cm
      (6.5 to 18). Average follow-up was 54 months (27 to 84). Bone union occurred at
      both ends of the grafted fibula in all 11 patients, with an average time to union
      of 5.5 months (3 to 8). We did not see a fracture of the grafted fibula. Two
      patients had postoperative complications; the graft dislodged in one and
      laryngeal oedema occurred two days after operation in the other. A vascularised
      fibular strut graft provides a biomechanically stable and long-standing support
      in spinal fusion because the weak phase of creeping substitution does not take
      place in the graft.

PMID- 9020445
TI  - Spinal cord monitoring in operations for neuromuscular scoliosis.
AB  - We reviewed retrospectively the role of monitoring of somatosensory spinal evoked
      potentials (SSEP) in 99 patients with neuromuscular scoliosis who had had
      operative correction with Luque-Galveston rods and sublaminar wiring. Our
      findings showed that SSEP monitoring was useful and that a 50% decrease in the
      amplitude of the trace optimised both sensitivity and specificity. The detection
      of true-positive results was higher than in cases of idiopathic scoliosis, but
      the method was less sensitive and specific and there were more false-negative
      results. In contrast with the findings in idiopathic scoliosis, recovery of the
      trace was associated with a 50% to 60% risk of neurological impairment. Only one
      permanent injury occurred during the use of this technique, and any temporary
      impairment resolved within two months.

PMID- 9020446
TI  - Management of fibular hemimelia: amputation or limb lengthening.
AB  - We reviewed retrospectively 22 patients (23 limb segments) with fibular hemimelia
      treated by amputation or limb lengthening to evaluate these methods of treatment.
      There were 12 boys and 10 girls, all with associated anomalies in the lower
      limbs. Twelve patients (13 limb segments) had early amputation and prosthetic
      fitting and ten had tibial lengthening using the Ilizarov technique. At the
      latest follow-up, the twelve patients who had amputation were functioning well
      and had few complications. The ten patients who had lengthening had suffered
      numerous complications, and all had needed either further corrective surgery or
      to wear braces or shoe-raises. Two of the ten lengthened limbs required late
      amputation for poor function or cosmesis. There were fewer hospital admissions,
      clinic visits, and periods of absence from school in the amputation group. Our
      findings suggest that amputation is a more effective method of management than
      limb-lengthening in severe fibular hemimelia. The Ilizarov method is an
      attractive alternative for selected patients, but its exact role is not yet
      established. One problem is that families often have unrealistic expectations of
      the surgical and prosthetic technology available and may refuse amputation when
      this has been recommended.

PMID- 9020447
TI  - Spontaneous regeneration of the lateral malleolus after traumatic loss in a three
      year-old boy: a case report with seven-year follow-up.
AB  - We describe a three-year-old boy who had spontaneous regeneration of the entire
      lateral malleolus after injury, including the epiphysis, physis and metaphysis.

PMID- 9020448
TI  - Total shoulder replacement in rheumatoid disease: 7- to 13-year follow-up of 37
      joints.
AB  - We made a prospective study of 58 consecutive Neer II total shoulder replacements
      in 49 rheumatoid patients. Cemented glenoid and press-fit humeral components had
      been used. After a mean follow-up of 9.5 years (7 to 13), 11 patients (15
      shoulders) had died, one shoulder had been arthrodesed and five patients (five
      shoulders) had been lost to follow-up. Of the remaining 37 shoulders 29 were
      painfree or had only slight discomfort, four had pain on unusual activity, and
      four had moderate or severe pain. There were satisfactory improvements in the
      mean range of active elevation (53 degrees to 75 degrees) and external rotation
      (5 degrees to 38 degrees); satisfactory performance of the activities of daily
      living had been maintained throughout follow-up. Radiographs showed loosening in
      ten shoulders of nine glenoid and nine humeral components but of these only three
      had significant symptoms. Three loose glenoid components and two loose humeral
      components required revision. We consider that the Neer total shoulder
      replacement provides a reasonable medium to long-term outcome in rheumatoid
      arthritis, but recommend that the humeral component should be routinely cemented.

PMID- 9020449
TI  - Treatment of chronic rotator-cuff impingement by arthroscopic subacromial
      decompression.
AB  - We report a prospective study of 49 patients who had arthroscopic subacromial
      decompression for chronic rotator-cuff impingement. All patients were assessed
      preoperatively and at 3, 6 and 12 months using the modified UCLA shoulder score.
      The dominant arm was affected in 35 patients, but only 13 recognised overuse as a
      cause of their shoulder pain. Before operation, the UCLA shoulder score was poor
      or fair in all patients. After three months only 28% of patients had satisfactory
      relief of symptoms but at one year 85% of patients examined had a good or
      excellent result. Patients with calcific tendonitis recovered more quickly: 93%
      reported a good result at six months. We conclude that arthroscopic subacromial
      decompression is an effective form of treatment, but that patients should be
      warned that recovery from surgery may be prolonged.

PMID- 9020450
TI  - Isokinetic strength after tears of the supraspinatus tendon.
AB  - We measured the isokinetic strength of abduction, adduction, internal rotation,
      and external rotation in ten patients with full-thickness tears of the
      supraspinatus and ten with partial-thickness tears. The measurements were
      repeated after intra-articular or intrabursal injection of local anaesthetic.
      Pain blocks produced significant increases in strength in both full and partial
      thickness tears. After the block, the strength in full-thickness tears compared
      with the opposite side was 67% to 81% in abduction and 67% to 78% in external
      rotation, both significantly smaller than those on the uninvolved side (p =
      0.0064, p = 0.0170). In partial-thickness tears the strength after the block
      ranged from 82% to 111%, with no significant differences between the involved and
      uninvolved sides. The decreases in strength of 19% to 33% in abduction and 22% to
      33% in external rotation after full-thickness tears appear to represent the
      contribution of supraspinatus to the strength of the shoulder.

PMID- 9020451
TI  - Primary Charnley total hip arthroplasty for congenital dysplasia: effect of
      improved techniques of cementing.
AB  - We performed Charnley total hip arthroplasties on 64 patients (71 hips) between
      1976 and 1984 for moderate congenital acetabular dysplasia in which a
      superolateral cement thickness of less than 20 mm was expected when the cup was
      placed in the true acetabulum at an angle of 45 degrees. Of these, 59 hips were
      examined 10 to 17 years after operation; 37 (group A) had been operated on
      between 1976 and 1982 using Charnley's original technique of cementing the
      acetabulum and 22 (group B) between 1983 and 1984 using more modern techniques.
      In group A, aseptic loosening of the socket was observed in ten hips (27.0%) and
      the 17-year survival rate was 81.5%. In group B, loosening was noted in only one
      socket (4.5%) and the 13-year survival rate was 100%. The improved techniques
      produced significantly better long-term results in fixation of the cup in
      dysplastic hips without bone grafting.

PMID- 9020452
TI  - Hydroxyapatite in revision of total hip replacements with massive acetabular
      defects: 4- to 10-year clinical results.
AB  - Hydroxyapatite (HA) granules of 100 to 300 microm, 0.9 to 1.2 mm and 3.0 to 5.0
      mm were mixed in a ratio of 10:45:45 and packed into massive bone deficiencies in
      revision operations for total hip arthroplasty. We did not use additional graft
      or cup support for deficiencies of the lateral and medial wall. The procedure was
      carried out in 40 hips between 1986 and 1992. The radiographic spaces seen at the
      interface between HA and bone immediately after surgery disappeared within three
      months. Some spaces appeared between HA granules near the bone in the lateral
      part of two joints, and three sockets migrated in patients with severe segmental
      and cavitary deficiencies. Direct bonding of HA to bone was observed
      radiologically without morphological changes, except in the three joints with
      migration. All patients could walk without pain but the three with definite
      loosening needed crutches.

PMID- 9020453
TI  - Pain levels after total hip replacement: their use as endpoints for survival
      analysis.
AB  - We have assessed the relative value of various outcome measures after THR, by the
      analysis of follow-up data from over 2000 patients. They had been reviewed
      clinically and radiologically six months after operation, at one year, and then
      every two years, some for 16 years. At each review their pain level, stiffness
      and opinion of progress were scored and a radiograph taken. We found that pain
      level was the most informative outcome as a predictor of revision and correlated
      well with the patients' opinions. We made a comparison between the six types of
      implant in the series, using survival analysis and log-rank testing with
      different pain levels as endpoints. This analysis revealed differences which were
      not detected by survival analysis using the traditional endpoint of revision. We
      therefore recommend the use of different levels of pain as the main outcome
      measures after total hip replacement.

PMID- 9020454
TI  - Tourniquets in forefoot surgery: less pain when placed at the ankle.
AB  - We studied perioperative pain and postoperative neurological changes after
      surgery for hallux valgus in 50 patients operated on under local ankle block.
      Patients were randomised to have the pneumatic tourniquet either at calf level or
      just above the ankle. The cuffs were inflated to 100 mmHg above systolic blood
      pressure. One patient was withdrawn from the study after randomisation. Areas of
      pain, paraesthesia and numbness were marked by patients on a diagram of the foot
      before operation and at six and ten weeks after operation. Both positions of the
      tourniquet gave an excellent bloodless field. The proximal tourniquet gave
      significantly greater discomfort (p < 0.01) during the operation, after 10, 20
      and 30 minutes. Application of the cuff at the ankle gave no relative increase in
      areas of numbness and paraesthesia at six and ten weeks. An ankle tourniquet
      gives less discomfort with no increase in the incidence of nerve injury.

PMID- 9020455
TI  - An unusual complication of total knee replacement: a case report.
AB  - After total knee replacement a 57-year-old woman developed increasing pain in her
      left calf on exercise. This was due to erosion of the popliteal artery by a spur
      of cement. Removal of the spur with resection and Dacron grafting of the damaged
      section of the vessel cured her symptoms.

PMID- 9020456
TI  - Extradigital glomus tumour causing thigh pain: a case report.
AB  - Glomus tumours are rare and benign, arising from a neuromyoarterial glomus body,
      most commonly in the hand. We report a patient with such a tumour in an atypical
      site, the right vastus lateralis. Pain was aggravated by muscle contraction, and
      ultrasonography and MRI were required to locate the lesion accurately. Surgical
      excision gave immediate pain relief.

PMID- 9020457
TI  - Joint load considerations in total knee replacement.
AB  - Estimates of knee joint loadings were calculated for 12 normal subjects from
      kinematic and kinetic measures obtained during both level and downhill walking.
      The maximum tibiofemoral compressive force reached an average load of 3.9 times
      body-weight (BW) for level walking and 8 times BW for downhill walking, in each
      instance during the early stance phase. Muscle forces contributed 80% of the
      maximum bone-on-bone force during downhill walking and 70% during level walking
      whereas the ground reaction forces contributed only 20% and 30% respectively.
      Most total knee designs provide a tibiofemoral contact area of 100 to 300 mm2.
      The yield point of these polyethylene inlays will therefore be exceeded with each
      step during downhill walking. Future evaluation of total knee designs should be
      based on a tibiofemoral joint load of 3.5 times BW at 20 degrees knee flexion, 8
      times BW at 40 degrees and 6 times BW at 60 degrees.

PMID- 9020458
TI  - Substance P level in synovial fluid may predict pain relief after knee
      replacement.
AB  - Substance P is readily detected in the synovial fluid of the knee in which it
      acts as a powerful inflammatory agent in response to injury and disease. It may
      be an objective predictor of pain after knee replacement surgery. The level of
      substance P was measured in the synovial fluid in both knees of 114 patients
      having unilateral and in 86 patients having bilateral total knee replacement for
      osteoarthritis. All had severe pain in the knee to be replaced and joint
      destruction. Substance P was elevated in 73% of replaced knees but not in normal
      or asymptomatic knees. Good or excellent pain relief was achieved in 97% of
      patients with an elevated preoperative level of substance P and in 61% of those
      with a normal preoperative level (p < 0.05 compared with preoperative values).

PMID- 9020459
TI  - Stress shielding after total knee replacement may cause bone resorption in the
      distal femur.
AB  - Inadequate bone stock is often found in revision surgery of femoral components of
      total knee replacements. Our aim was to test the hypothesis that these
      remodelling patterns can be explained by stress shielding, and that prosthetic
      bonding characteristics affect maintenance of bone mass. We made a three
      dimensional finite-element model of an average male femur with a cemented femoral
      knee component. This model was integrated with iterative remodelling procedures.
      Two extreme prosthetic bonding conditions were analysed and gradual changes in
      bone density were calculated. The long-term bone loss under the femoral knee
      component resembled clinical findings which confirms the hypothesis that stress
      shielding can cause distal femoral bone loss. Our study predicts, contrary to
      clinical findings, that an equilibrium situation is not reached after two years,
      but that bone resorption may continue. This hidden bone loss may be so drastic
      that large reconstructions are needed at the time of revision.

PMID- 9020460
TI  - Uptake of 99mTc-MDP after uncemented hip arthroplasty: a quantitative analysis of
      findings around the femoral component in asymptomatic patients.
AB  - We studied the pattern of 99mTc-methylene diphosphonate uptake around uncemented
      femoral components in 44 asymptomatic hip arthroplasties, performing isotope
      scans at intervals from 4 to 48 months after operation. We used phase-II images
      obtained with a high-resolution gamma camera and measured the activity in various
      zones using a specially designed computer program. The components studied at 4,
      6, 9 and 12 months were coated with hydroxyapatite (HA) and those studied at 18,
      24, 36 and 48 months were not coated. We found a statistically significant fall
      in activity between four and six months around HA-coated prostheses in all five
      femoral periprosthetic zones. After six months activity was relatively uniform,
      but remained higher than that in normal femoral bone at 48 months in non-coated
      prostheses. We discuss the application of these patterns in the evaluation of
      painful cementless hip arthroplasties.

PMID- 9020461
TI  - Radio-opaque agents in bone cement increase bone resorption.
AB  - A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous
      membrane which surrounds an aseptically loose cemented implant. This is in
      response to particles of polymethylmethacrylate (PMMA) bone cement and other
      biomaterials. We have previously shown that monocytes and macrophages responding
      to particles of bone cement are capable of differentiating into osteoclastic
      cells which resorb bone. To determine whether the radio-opaque additives barium
      sulphate (BaSO4) and zirconium dioxide (ZrO2) influence this process, particles
      of PMMA with and without these agents were added to mouse monocytes and
      cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation,
      as shown by the presence of the osteoclast-associated enzyme tartrate-resistant
      acid phosphatase (TRAP) and lacunar bone resorption, was observed in all
      cocultures. The addition of PMMA alone to these cocultures caused no increase in
      TRAP expression or bone resorption relative to control cocultures. Adding PMMA
      particles containing BaSO4 or ZrO2, however, caused an increase in TRAP
      expression and a highly significant increase in bone resorption. Particles
      containing BaSO4 were associated with 50% more bone resorption than those
      containing ZrO2. Our results suggest that radio-opaque agents in bone cement may
      contribute to the bone resorption of aseptic loosening by enhancing macrophage
      osteoclast differentiation, and that PMMA containing BaSO4 is likely to be
      associated with more osteolysis than that containing ZrO2.

PMID- 9020462
TI  - Ceramic-ceramic and metal-polyethylene total hip replacements: comparison of
      pseudomembranes after loosening.
AB  - We made a semiquantitative study of the comparative histology of pseudomembranes
      from 12 loose cemented ceramic-ceramic and 18 metal-polyethylene total hip
      replacements. We found no significant difference in cellular reaction between the
      two groups, but there was a major difference in the origin of the particulate
      debris. In the metal-polyethylene group, polyethylene of articular origin was
      predominant, while in the ceramic-ceramic group the cellular reaction appeared to
      be a response to zirconia ceramic particles used to opacify cement used for
      fixation. Isolation and characterisation of the debris showed that the zirconia
      particles formed the greatest proportion (76%) in ceramic-ceramic hips, while
      alumina debris of articular origin formed only 12%. Our study has indicated that
      aseptic loosening of ceramic cups is not due to a response to debris generated at
      the articular interface, but to mechanical factors which lead to fragmentation of
      the cement.

PMID- 9020463
TI  - Joint motion and surface contact area related to component position in total hip
      arthroplasty.
AB  - A three-dimensional computer model of a total hip replacement was used to examine
      the relationship between the position of the components, the range of motion and
      the prosthetic joint contact area. Horizontal acetabular positions with small
      amounts of acetabular and femoral anteversion provide the largest contact areas,
      but result in limited joint movement. These data will allow surgeons to select
      implant positions that will provide the largest possible joint contact area for a
      given joint range of motion although these are conflicting goals. In some
      component positions a truncated spherical prosthetic head resulted in smaller
      contact areas than a completely spherical head.

PMID- 9020464
TI  - Sensory and sympathetic innervation of the vertebral endplate in patients with
      degenerative disc disease.
AB  - We obtained intervertebral discs with cartilage endplates and underlying
      cancellous bone at operation from patients with degenerative disc disease and
      then used immunohistochemical techniques to localise the nerves and nerve endings
      in the specimens. We used antibodies for the ubiquitous neuronal protein gene
      product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify
      autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to
      identify sensory nerves. Blood vessels were identified by immunoreactivity with
      platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group
      with no known history of chronic back pain, nerve fibres immunoreactive to PGP
      9.5 and neuropeptide Y were most closely related to blood vessels, with
      occasional substance P and CGRP immunoreactivity. In patients with severe back
      pain and markedly reduced disc height, proliferation of blood vessels and
      accompanying nerve fibres was observed in the endplate region and underlying
      vertebral bodies. Many of these nerves were immunoreactive to substance P or
      CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen
      unrelated to blood vessels. Quantification by image analysis showed a marked
      increase in CGRP-containing sensory nerve fibres compared with normal control
      subjects. We speculate that a chemotactic response to products of disc breakdown
      is responsible for the proliferation of vascularity and CGRP-containing sensory
      nerves found in the endplate region and vertebral body adjacent to degenerate
      discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as
      pain-transmitting effects. The increase in sensory nerve endings suggests
      increase in blood flow, perhaps as an attempt to augment the nutrition of the
      degenerate disc. The increase in the density of sensory nerves, and the presence
      of endplate cartilage defects, strongly suggest that the endplates and vertebral
      bodies are sources of pain; this may explain the severe pain on movement
      experienced by some patients with degenerative disc disease.

PMID- 9020465
TI  - The effects of posterior fixation on internal intervertebral disc mechanics.
AB  - Posterior fixation of intervertebral discs is used to treat, and occasionally
      diagnose, discogenic pain since it is thought that it will reduce the internal
      loading of the discs in vitro. We measured the internal loading of ten
      intervertebral discs using stress profilometry under simulated physiological
      loads and then after posterior fixation. Partial discectomies were performed to
      simulate advanced disc degeneration and the sequence repeated. Posterior fixation
      had very little effect on the magnitude of the loads acting on the disc and none
      when disc degeneration was simulated. It did, however, reduce bulging of the
      anterior annulus under combined bending and compression (p < 0.03). Recent
      experiments in vivo have shown that discogenic pain is associated with abnormal
      bulging of the annulus which suggests that the clinical benefit of fixation may
      be due to this.

PMID- 9020466
TI  - Contamination of bone allografts: analysis of incidence and predisposing factors.
AB  - We analysed the bacterial contamination of 1999 bone allografts retrieved from
      200 cadaver donors under sterile operating conditions. The effect of various
      factors on the relative risk of contamination was estimated using a multiple
      logistic regression model. Organisms of low pathogenicity were cultured from 50%
      of the grafts and of high pathogenicity from 3%. The risk of contamination with
      low pathogenic organisms (mainly skin commensals) increased by a factor of 1.6
      for each member added to the procurement team. The risk of contamination with
      high pathogenic organisms (mainly contaminants from the gastrointestinal tract)
      was 3.4 times higher in donors with a traumatic cause of death and 5.2 times
      higher in those with a positive blood culture. Preceding organ procurement did
      not significantly influence the risk of contamination. Rinsing the graft with an
      antibiotic solution was not an effective decontamination method. The major source
      of contamination is exogenous and is strongly influenced by the procurement team.
      Contamination from endogenous sources can be controlled by donor selection. We
      discuss methods that can be used to decrease contamination and the rate of
      discarding of bone allografts.

PMID- 9020467
TI  - A new radiographic method of measuring carpal collapse.
AB  - We assessed carpal collapse by measuring the capitate-radius (CR) distance on
      standard plain radiographs. This new method required validation of diagnostic
      accuracy, so we compared it with the method of Nattrass et al known as revised
      carpal height (RCH). We studied wrist radiographs from 16 normal subjects and 11
      patients with unilateral Kienbock's disease. We found that there was a
      significant difference in the left/right CR index between the normal wrists and
      those with Kienbock's disease (p < 0.001). The use of left/right RCH index showed
      no significant difference (p = 0.30). Diagnostic accuracy was shown to be higher
      for the CR index using ROC curves. We then assessed 40 normal wrists and found
      the mean CR index to be 0.999 +/- 0.034, and suggest that values less than 0.92
      are abnormal. The CR index can be used for diagnosis in unilateral carpal
      collapse, and for monitoring progress where the condition is bilateral.

PMID- 9020468
TI  - Reamed or unreamed nailing for closed tibial fractures.

PMID- 9020469
TI  - Reamed or unreamed nailing for closed tibial fractures.

PMID- 9020470
TI  - Management of Perthes disease of late onset in southern India.

PMID- 9020471
TI  - Surgical resection of primary soft-tissue sarcoma.

PMID- 9020472
TI  - The effects of particulate polyethylene at a weight-bearing bone-implant
      interface.

PMID- 9020473
TI  - Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma
      xenografts: possible role of decreased oxygen consumption.
AB  - In contrast to reports of extensive hypoxia in human gliomas in situ measured by
      pO2 histography, non-invasive methods of assessing glioma oxygenation, including
      nitroimidazole binding, have yielded surprisingly contradictory results. In order
      to investigate the relationship of necrosis, hypoxia, nitroreductase activity and
      cellular respiration in human gliomas, subcutaneous models using the human glioma
      cell lines M059K, M006 and M010b were developed in the murine SCID host.
      Intracranial growth of the M006 line was achieved in nude rats. The
      nitroreductive capacity of glioma cell lines was assessed and found to be similar
      to transplanted tumours previously reported in the literature. This suggests that
      if substantial numbers of viable hypoxic cells were present in situ in gliomas,
      then nitroimidazole-binding techniques should be capable of identifying them.
      Inter-tumour variability in the amount of necrosis was seen. M006 xenografts
      growing in subcutaneous and intracranial sites revealed extensive necrotic
      regions histologically, some of which were surrounded by cells labelled heavily
      for [3H]misonidazole, while other areas were lightly labelled. Similar binding
      patterns were seen for subcutaneous M059K tumours, while subcutaneous M010b
      tumours display necroses of which almost all were surrounded by heavily labelled
      cells. The oxygen consumption rates of tumour cell lines grown in vivo, in which
      venous pO2 concentrations are of the order of 2-5%, were two to sevenfold less
      than those of the same lines grown as monolayers in vitro under oxygen
      concentrations of 18%. We postulate that glioma cell lines behave as 'oxygen
      conformers', in that their rate of oxygen consumption appears to vary with the
      availability of oxygen. Together with the misonidazole-binding data, the results
      in this glioma tumour model are consistent with coordinate inhibition or down
      regulation of respiration under moderate hypoxia.

PMID- 9020474
TI  - The relationship between extracellular lactate and tumour pH in a murine tumour
      model of ischaemia-reperfusion.
AB  - We have studied the relationship between extracellular lactate (LACTe) and
      extracellular pH (pHe) in murine tumours after vascular occlusion (clamping)
      followed by reperfusion. In tumours occluded at ambient room temperature, LACTe,
      measured by microdialysis, increased linearly with time and correlated strongly
      with the acidification of the extracellular compartment (r=0.97, P<0.03, n=4).
      Significant decrease in LACTe was evident following removal of occlusion at room
      temperature and is consistent with vascular reperfusion. Occlusion at 35 degrees
      C, i.e. to maintain tumour temperature during occlusion, resulted in an initial
      increase in LACTe, which mirrored a rapid reduction in pHe. However further
      reductions in pHe occurred without increase in LACTe. During vascular occlusion,
      tumour adenine nucleotide pool decreased and AMP accumulated. AMP subsequently
      decreased in the 35 degrees C group and this may contribute to the observed
      differences in accumulation of LACTe, and capacity to recover from vascular
      occlusion, between the two treatment groups. These data show that extracellular
      lactate concentration is a good predictor for tumour pH when adequate energy
      sources are available within the tumour. However, under conditions of more severe
      stress, resulting in abolition of primary energy stores and cell death, the pHe
      continues to decline in the absence of a corresponding accumulation of
      extracellular lactate. This emphasizes the fact that other processes, apart from
      lactate production, can contribute to reduction in extracellular pH.

PMID- 9020475
TI  - In vivo anti-tumour effect of 3'-sulphonoquinovosyl 1'-monoacylglyceride isolated
      from sea urchin (Strongylocentrotus intermedius) intestine.
AB  - Extracts from sea urchin intestine were screened for new anti-tumour drugs. Four
      glycolipids, 3'-sulphonoquinovosyl-1', 2'-diacylglyceride (A-4), 3'
      sulphonoquinovosyl-1'-monoacylglyceride (2'-lyso A-4, A-5), NeuGc(alpha)2
      6Glc(beta)1-1ceramide (A-6) and HSO3-8NeuGc(alpha)2-6Glc(beta)1-1ceramide (A-7),
      were isolated from the intestine of sea urchin, Strongylocentrotus intermedius,
      and characterized by means of proton nuclear magnetic resonance spectroscopy and
      fast atom bombardment mass spectrometry. When tested for cytotoxic activity
      against tumour cells in vitro, A-5 showed significant activity, but A-4, -6 and 
      7 did not. In addition, the hydrophilic derivatives of A-4 or -5 had no
      cytotoxicity. Furthermore, the anti-tumour effects on nude mice bearing solid
      tumours of a human lung adenocarcinoma cell line A-549 were evaluated in vivo
      using A-4 and -5. As a result, A-5 was found to be significantly effective in
      suppressing the growth of solid tumours, whereas A-4 had no effect.
      Pathologically, the solid tumours showed haemorrhagic necrosis areas after
      treatment with A-5. In this study, we have demonstrated the anti-tumour effect of
      sulphonoquinovosyl-lysoglyceride (A-5), which provides important information that
      this sulpholipid could be a useful drug for cancer chemotherapy.

PMID- 9020476
TI  - Multifactorial mechanism for the potentiation of cisplatin (CDDP) cytotoxicity by
      all-trans retinoic acid (ATRA) in human ovarian carcinoma cell lines.
AB  - All-trans retinoic acid (ATRA) has been previously shown to inhibit the
      proliferation of some human ovarian carcinoma cell lines, and this inhibition was
      accompanied by cellular changes that were indicative of differentiation (Caliaro
      et al, 1994). In this work, a pretreatment of these adenocarcinoma cells with
      ATRA, for their respective doubling time, enhanced cisplatin (CDDP) cytotoxicity
      in the cell ines that were sensitive to its antiproliferative effect, but not in
      the ATRA-resistant ones. Results were assessed using median effect analysis in
      two ATRA-sensitive cell lines (OVCCR1 and NIHOVCAR3 cells) and in one ATRA
      insensitive cell line (IGROV1 cells). Synergy between these two agents was
      observed only in cells sensitive to ATRA, regardless of their relative
      sensitivity to CDDP. Potential mechanisms for this synergy were investigated.
      ATRA did not increase the cellular platinum content, did not decrease the
      cellular glutathione and had no influence on the metallothionein IIA mRNA levels
      in NIHOVCAR3 cells. Moreover, the protein kinase C (PKC) activity was modulated
      by this differentiating agent in all cell lines tested, indicating that this
      activity was not directly involved in this potentiation. However, an ATRA
      inhibition of glutathione-S-transferase activity associated with an increase in
      the total DNA adducts formation could explain the potentiation of the CDDP
      cytotoxicity observed in NIHOVCAR3 cells. Finally, the ATRA modulation of the
      epidermal growth factor (EGF) receptor mRNA level could also be implicated in
      this synergy.

PMID- 9020477
TI  - A detailed analysis of the role of K-ras gene mutation in the progression of
      colorectal adenoma.
AB  - To elucidate the role of ras gene mutations during the early stage of colorectal
      tumour progression, K-ras gene mutations were analysed in 32 benign adenomas and
      36 adenomas with focal carcinoma in the colorectum by microscraping of
      histologically pure regions from tissue sections, polymerase chain reaction
      restriction fragment length polymorphism and in part by direct sequencing.
      Several regions were scraped out and analysed when an adenoma contained areas
      with different grades of dysplasia. The frequencies of K-ras gene mutation in
      mild dysplasia, moderate dysplasia and focal carcinoma were 19% (7/36), 51%
      (25/49) and 39% (14/36) respectively. The K-ras gene status was heterogeneous in
      4 of the 11 benign adenomas from which multiple samples were obtained, and
      mutations were always found in the regions with more advanced dysplasia in these
      adenomas. Thirteen of the 36 adenomas with focal carcinoma showed heterogeneity
      of mutations between the adenoma region and the focal carcinoma. Seven of which
      had mutations only in the adenoma region. These findings indicated that the K-ras
      gene mutations occur during the late stage of adenoma progression and may confer
      a more advanced morphological phenotype of adenoma, but these mutations are not
      mainly involved in malignant transformation from adenoma to carcinoma.

PMID- 9020478
TI  - Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA
      and DHA.
AB  - We investigated the effects of low-dose eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) on the incidence and growth of 7,12
      dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat
      (HF) diet. We also examined the effects of these treatments on the fatty acid
      composition of tumour and serum. Tumour incidence was significantly decreased by
      the administration of low-dose EPA and DHA, whereas their inhibitory effects on
      tumour growth did not reach significance. Serum arachidonic acid (AA) level was
      decreased by the administration of low-dose EPA and tended to be decreased by the
      administration of low-dose DHA, whereas tumour AA levels were not changed. The
      administration of low-dose EPA and DHA may be useful for inhibiting the incidence
      of breast cancer.

PMID- 9020479
TI  - Midkine induces the transformation of NIH3T3 cells.
AB  - Midkine (MK) is a heparin-binding growth factor and is frequently expressed at
      high levels in many human carcinomas. To investigate further the roles of MK in
      the regulation of cell growth, we introduced MK expression in NIH3T3 cells. A
      mixture of transfectants of an MK expression vector, but not a control vector,
      formed colonies in soft agar, showed an elevated cell number at confluence, and
      formed tumours in nude mice. An interesting characteristic of the transformed
      cells was that they became spontaneously detached from the culture dish
      substratum. In the transformed cells, MK was not only secreted, but also
      localized, in the perinuclear region as spots. The present data indicate that MK
      has the potential to transform NIH3T3 cells and suggest that overexpression of
      the MK gene may promote unregulated cell growth in vivo.

PMID- 9020480
TI  - Somatostatin receptor subtype mRNA expression in human colorectal cancer and
      normal colonic mucosae.
AB  - Somatostatin analogues may be useful novel agents in the systemic treatment of
      advanced colorectal cancer, as somatostatin inhibits proliferation in a wide
      variety of cell types. Here, we report the expression profiles of somatostatin
      receptor mRNAs in 32 pairs of malignant and normal colonic epithelia. Receptor
      subtype 2 (hSSTR2) mRNA was detected throughout nearly 90% of both malignant and
      normal tissue by reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ hybridization. Subtype 5 (hSSTR5) mRNA was detected in 46% and 45% of tumour
      and mucosal samples respectively, but in 75% (9/12) of early-stage tumours
      (tubulovillous adenomas, Dukes' A and B) compared with 31% (5/16) of late-stage
      tumours (Dukes' C and 'D' tumours), 0.05>P>0.025 (chi2 with Yates' correction).
      There was also reduced expression of hSSTR5 in samples of metastatic tumour (11%,
      1/9) compared with all tumour samples (56%, 18/32) 0.025>P>0.01 (chi2 with Yates'
      correction). Other hSSTRs (1, 3 and 4) were expressed infrequently. Thus, hSSTR2
      expression is retained after malignant transformation in colonic epithelium and,
      although it may potentially be a target for antiproliferative therapy, its
      ubiquitous expression militates against this. hSSTR5 warrants investigation as a
      tumour suppressor.

PMID- 9020481
TI  - Apoptosis, cell proliferation and expression of Bcl-2 and Bax in gastric
      carcinomas: immunohistochemical and clinicopathological study.
AB  - To clarify the relation between bcl-2 and bax protein (Bcl-2 and Bax) expression
      with regard to apoptosis and cell proliferation, 82 gastric carcinomas were
      immunohistochemically investigated. The significance of apoptosis for biological
      behaviour of the tumours was also examined. The apoptotic indices (AIs) were
      significantly lower in early-stage than in advanced-stage lesions (P<0.05), being
      positively correlated with the mitotic indices (MIs) (r=0.447, P<0.001). No
      association between either AIs or MIs and tumour size (diameter of intramural
      spreading) was noted. The AIs in the high Bcl-2-immunoreactive score group were
      significantly smaller than in either the low or the negative categories, whereas
      they were relatively elevated in the high Bax score group. In addition, an
      inverse correlation between Bcl-2 and Bax expression was revealed for both AIs
      and MIs. Although depth of tumour invasion and lymph node status were clearly
      associated with favourable outcome, no relation between survival rates and
      average values of either AIs or MIs, or immunoreactive scores for Bcl-2 and Bax
      was observed. These results indicate that in gastric carcinomas, apoptosis is
      closely associated with cell proliferation and expression of Bcl-2 and Bax, but
      appears likely to have no particular biological significance as a prognostic
      factor.

PMID- 9020483
TI  - Stimulation of tetrapyrrole synthesis in mammalian epithelial cells in culture by
      exposure to aminolaevulinic acid.
AB  - Tetrapyrrole synthesis in CNCM-1221 cells exposed to 0.6 mM aminolaevulinic acid
      (ALA) was found to be approximately linear over a 6-h period of incubation. The
      rate was not significantly affected by cell density over a range of 0.015 to 0.15
      x 10(6) cells cm(-2) (final cell density). Tetrapyrrole synthesis was not
      affected by GABA or glutamic acid in concentrations up to 6 mM and 2.72 mM
      respectively, suggesting that these amino acids, which are similar in structure
      to ALA, do not competitively inhibit the ALA uptake pathway in these cells. Pre
      exposure to haem arginate (up to 100 microM) was inhibitory, presumably by
      suppression (through the inhibition of ALA synthase) of an endogenous component
      of the response. The ALA-stimulated response was not modified by co-exposure to
      AIA (up to 100 mg ml(-1)). Despite significant reduction of protein synthesis,
      the porphyrinogenic response of cells exposed to ALA was unaffected by
      cycloheximide (10 microg ml(-1)) or actinomycin D (10 microg ml(-1)) even when
      cells were preincubated with these agents for 3 h before ALA exposure. Fetal
      bovine serum (10%) inhibited tetrapyrrole synthesis by 30% but increased the rate
      of porphyrin export by cells by a factor of 1.5. The uptake of [14C]ALA was shown
      to be strongly influenced by the density of the cultures. In dense cultures
      (final cell density of approximately 0.15 x 10(6) cells cm(-2)), the ALA uptake
      rate was less than 0.8 compared with a maximum rate of 4.2 fmol per cell h(-1) at
      a cell density of 0.02 x 10(6) cells cm(-2). Since tetrapyrrole synthesis is less
      affected than ALA uptake by cell density, the resultant discrepancy in ALA
      incorporation occurring in dense cultures implies that endogenous ALA synthesis
      is induced in these cells. ALA uptake was not affected by cycloheximide or
      actinomycin D in serum-free conditions. However, fetal bovine serum decreased
      external ALA uptake by about 50%. This effect was abrogated by preincubation with
      cycloheximide.

PMID- 9020482
TI  - Infiltration of mononuclear inflammatory cells into primary colorectal
      carcinomas: an immunohistological analysis.
AB  - Local immunoregulation mediated by mononuclear tumour-infiltrating cells is
      considered of importance for tumour progression of colorectal cancer, although
      the balance between immunosuppressor and cytotoxic activities is unclear.
      Colorectal cancers from 26 patients were investigated using a panel of monoclonal
      antibodies in order to identify subsets of mononuclear inflammatory cells and to
      study their pattern of distribution in relation to tumour stage and cytotoxic
      immune reactivity against the tumour. In all but five tumours, mononuclear cells,
      lymphocytes or monocytes were present in fairly large numbers, particularly in
      the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+
      subset. Infiltration near the tumour cells was found in four cancers only.
      Stromal infiltration of CD11c+ macrophages was found in all but eight tumours.
      Small regressive areas, in which the histological architecture of the tumours was
      broken down, were found in 17 tumours with intense or moderate infiltration by
      CD4+ lymphocytes or CD11c+ macrophages. Probably this destruction of tumour
      tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear
      cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+
      cells with macrophage morphology, but the latter were increasingly found in
      Dukes' class C and D disease. The occurrence of MHC II-positive macrophages and
      lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In
      contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B
      class tumours compared with Dukes' C and D. Four out of nine tumours of the
      latter stages showed a poor inflammatory reaction. The interpretation of our
      results is that the subsets of tumour-infiltrating mononuclear cells change with
      advancing Dukes' class and that the local immune control is gradually broken down
      in progressive tumour growth, even if some cytotoxic activity is still present.

PMID- 9020484
TI  - Enhanced expression of urokinase plasminogen activator and its receptor in
      pancreatic carcinoma.
AB  - Urokinase plasminogen activator (uPA) is a serine proteinase that has been
      suggested to play an important role in cancer invasion and metastasis. It binds
      to a specific membrane receptor denominated uPA receptor (uPAR). uPA activates
      plasminogen to form plasmin, which participates in tissue degradation and
      proteolysis. Binding of uPA to its receptor accelerates UPA's own activation from
      pro-uPA, enhancing the activity of the uPA/uPAR cascade. Using
      immunohistochemistry and Northern blot analysis, we analysed the role of uPA and
      uPAR in 30 human pancreatic cancers. Immunohistochemical analysis demonstrated
      moderate to strong immunostaining of both factors in most pancreatic cancers.
      Cancer lesions with signs of invasion exhibited the strongest immunohistochemical
      signals for both factors. In addition, in desmoplastic areas adjacent to the
      cancer cells, moderate uPA and uPAR immunoreactivity was detectable. Northern
      blot analysis revealed a sixfold and a fourfold increase in uPA and uPAR mRNA
      levels in pancreatic cancer, respectively, in comparison with normal controls
      (P<0.01). Correlation of the Northern blot data with the clinical parameters of
      the patients indicated that patients with concomitant overexpression of uPA and
      uPAR had a shorter post-operative survival (median 9 months; mean+/-s.d. 10.2+/
      3.6 months) than patients in whom only one or none of these factors were
      overexpressed (median 18 months; mean+/-s.d. 20.3+/-8.7 months) (P<0.002). Our
      data suggest that uPA and uPAR may serve as prognostic markers in human
      pancreatic cancer and that the marked overexpression of both factors may create
      an environment that enables pancreatic cancer cells to invade surrounding
      tissues.

PMID- 9020485
TI  - Alterations in DNA methylation are early, but not initial, events in ovarian
      tumorigenesis.
AB  - We compared global levels of DNA methylation as well as methylation of a specific
      locus (MyoD1) in ovarian cystadenomas, ovarian tumours of low malignant potential
      (LMP) and ovarian carcinomas to investigate the association between changes in
      DNA methylation and ovarian tumour development. As we realized that cystadenomas
      showed different methylation patterns from both LMP tumours and carcinomas, we
      verified their monoclonal origin as a means of confirming their true neoplastic
      nature. High-pressure liquid chromatographic (HPLC) analyses showed that global
      methylation levels in LMP tumours and carcinomas were 21% and 25% lower than in
      cystadenomas respectively (P = 0.0001 by one-way variance analysis). Changes in
      the methylation status of the MyoD1 locus were not seen in any of ten
      cystadenomas analysed but were present in five of ten LMP tumours and in five of
      ten carcinomas (P = 0.03). These findings suggest that alterations in DNA
      methylation are absent (or at least not as extensive) in ovarian cystadenomas,
      but are present in LMP tumours, the phenotypic features of which are intermediate
      between those of benign and malignant ovarian tumours. The results also emphasize
      the merit of distinguishing ovarian LMP tumours from cystadenomas, in spite of
      their similar clinical characteristics.

PMID- 9020486
TI  - Interphase fluorescence in situ hybridization improves the detection of malignant
      cells in effusions from breast cancer patients.
AB  - In diagnostic evaluation of effusions, difficulties are encountered when atypical
      reactive mesothelial cells have to be differentiated from malignant cells. We
      tested the impact of fluorescence in situ hybridization (FISH) to identify
      metastatic cells in breast cancer effusions by detection of numerical chromosomal
      changes. Pleural and ascitic fluid samples (n=57) from 41 breast cancer patients
      were concomitantly evaluated by routine cytology and FISH, using centromere
      specific probes representing chromosomes 7, 11, 12, 17 and 18. After setting
      stringent cut-off levels deduced from non-malignant control effusions (n=9), the
      rates of cells with true aneuploidy were determined in each effusion sample from
      breast cancer patients. The occurrence of aneuploid cells, as detected by FISH
      and indicative of malignancy, was correlated with the cytological findings.
      Routine cytology revealed malignancy in 60% of effusions. Using FISH, aneuploid
      cell populations could be observed in 94% of cytologically positive and in 48% of
      cytologically negative effusions, thus reverting diagnosis to malignancy. To
      confirm malignancy in cases with a low frequency of aneuploid cells, two-colour
      FISH was additionally performed and indeed showed heterogeneous chromosomal
      aneuploidy within single nuclei. We conclude that FISH is a valuable tool in the
      diagnosis of malignancy and may serve as an adjunct to routine cytological
      examination, as demonstrated here for breast cancer effusions.

PMID- 9020487
TI  - Comparative evaluation of markers of bone resorption in patients with breast
      cancer-induced osteolysis before and after bisphosphonate therapy.
AB  - The understanding of the pathophysiology and the monitoring of metastatic bone
      disease remains unsatisfactory. We compared several new markers of bone turnover
      in normocalcaemic patients with breast cancer-induced osteolysis before and after
      a single infusion of the bisphosphonate pamidronate. We studied 19 ambulatory
      patients with advanced breast cancer and extensive bone metastases who did not
      receive any systemic antineoplastic therapy. Pamidronate was administered at
      doses of 30, 60, 90 or 120 mg and the patients were followed weekly during a mean
      of 8 (range 4-10) weeks. Compared with healthy premenopausal women, the
      percentage of elevated values at baseline was 47% for fasting urinary calcium
      (uCa), 74% for hydroxyproline, 83% for CrossLaps (a new marker of type I collagen
      degradation) and 100% for the collagen cross-links (measured by high performance
      liquid chromatography), namely pyridinoline (Pyr) and deoxyPyr (D-Pyr).
      Pretreatment levels of uCa did not correlate significantly with any of the four
      markers of bone matrix resorption, whereas the correlations between these four
      markers were generally significant (r(s)=0.43-0.71). Alkaline phosphatase
      correlated significantly with markers of bone matrix resorption (r(s)=0.54-0.74).
      All parameters, except phosphaturia (uPi) and the bone formation markers
      (osteocalcin and alkaline phosphatase), fell significantly after pamidronate
      therapy, up to day 42 for hydroxyproline, D-Pyr and CrossLaps and day 56 for uCa.
      This longer lasting effect was probably due to the parathyroid hormone (PTH)
      surge following the decrease in serum calcium, implying that the decrease in uCa
      can overestimate the effects of bisphophonates on bone resorption. The decrease
      in bone turnover parameters was most marked for CrossLaps, indicating the
      potential of this new marker for monitoring therapy. Sequential determinations of
      markers of bone matrix resorption should be useful in delineating the optimal
      therapeutic schemes of bisphosphonates and for evaluating treatment effects on
      bone in cancer patients.

PMID- 9020488
TI  - Characteristics of the menstrual cycle at the time of surgery for breast cancer.
AB  - Hormone measurements during the menstrual cycle were assessed in six
      premenopausal women undergoing breast cancer surgery and ten controls to
      determine whether the stress of diagnosis and surgery influenced cycle
      characteristics. There was hormonal evidence for normal ovulation in all cancer
      and control women, although the length of the luteal phase of the cycle was
      prolonged because of a delay in menstruation in two cancer patients. The timing
      of surgery in the cycle did not influence the hormonal data. The hormonal
      characteristics of the menstrual cycle thus appear to be normally preserved in
      women during the month in which breast cancer surgery is performed.

PMID- 9020489
TI  - Peripheral neuropathy induced by combination chemotherapy of docetaxel and
      cisplatin.
AB  - Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as
      an antineoplastic agent, was administered in combination with cisplatin to 63
      patients in a dose-escalating study. As both drugs were known to be potentially
      neurotoxic, peripheral neurotoxicity was prospectively assessed in detail.
      Neuropathy was evaluated by clinical sum-score for signs and symptoms and by
      measurement of the vibration perception threshold (VPT). The severity of
      neuropathy was graded according to the National Cancer Institute's 'Common
      Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a
      predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At
      cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out
      of 35 patients developed a neuropathy which was mild in 15, moderate in ten and
      severe in one patient. Significant correlations were present between both the
      cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of
      neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The
      neurotoxic effects of this combination were more severe than either cisplatin or
      docetaxel as single agent at similar doses.

PMID- 9020490
TI  - A phase II study of recombinant interferon-beta (r-hIFN-beta 1a) in combination
      with 5-fluorouracil (5-FU) in the treatment of patients with advanced colorectal
      carcinoma.
AB  - The combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN-alpha) has
      reported activity in the treatment of advanced colorectal carcinoma. Laboratory
      studies of IFN-beta suggest that this agent may offer theoretical advantages over
      IFN-alpha in combination with 5-FU. A total of 27 patients with advanced or
      recurrent colorectal carcinoma were treated in a non-randomized open phase II
      study with a combination of 5-fluorouracil (750 mg m(-1) daily for 5 days as a
      continuous intravenous (i.v.) infusion followed, from day 15, by i.v. bolus 750
      mg m(-2) every 7 days) and recombinant interferon-beta [r-hIFN-beta-1a; 9 MIU
      (total dose) by subcutaneous injection from day 1 on every Monday, Wednesday and
      Friday throughout the treatment period]. Toxicity was less than that seen with
      this schedule of 5-FU in combination with IFN-alpha. Among 21 evaluable patients,
      four objective responses were seen. Recombinant human interferon-beta-1a in
      combination with 5-FU is an acceptable regimen in terms of toxicity. However, the
      study did not demonstrate a superior response rate when compared with previous
      reports of treatment with 5-FU alone or in combination with IFN-alpha.

PMID- 9020492
TI  - Tumour marker concentration at the start of chemotherapy is a stronger predictor
      of treatment failure than marker half-life: a study in patients with disseminated
      non-seminomatous testicular cancer.
AB  - We investigated the prognostic value of the serum half-life of human chorionic
      gonadotrophin (HCG) and alpha-fetoprotein (AFP) during induction chemotherapy and
      the relative prognostic importance of initial marker concentrations and marker
      half-life. Marker half-lives were calculated using two abnormal values observed
      between day 8 and day 22 of the first chemotherapy cycle. Moreover, analyses were
      carried out using day 43 as the second measurement point. Treatment failure at
      any time was chosen as the end point. The relative prognostic influence of marker
      half-lives and initial marker concentrations was tested in univariate and
      multivariate analyses. Half-lives were considered to be prolonged if > 3 days for
      HCG and > 6 days for AFP. In addition, we separated patients into those with half
      lives > 6 days for HCG and those with half-lives > 10 days for AFP to examine
      whether these long half-lives were associated with a poor prognosis. A group of
      669 patients treated with cisplatin combination chemotherapy was studied. Forty
      two per cent of the patients had normal HCG and 37% had normal AFP at the start
      of chemotherapy. At day 22, HCG was still elevated in 138 patients and AFP in
      211. At day 43, the numbers of these patients were 35 and 80 respectively. Based
      on the measurements obtained on day 8 and day 22, a half-life of HCG > 3 days or
      > 6 days and/or a half-life AFP > 6 days or > 10 days did not accurately predict
      treatment failure (P=0.413 and P=0.851, respectively; values obtained using tests
      for trend). However, initial marker concentrations of HCG and/or AFP > 1000 IU l(
      1) were highly significant prognosticators for treatment failure (P=0.001 and P <
      0.001 respectively), independent of half-life values. Half-lives calculated with
      the values obtained on day 43 did not contribute to the accuracy of the
      prediction of treatment failure. We conclude that half-lives of HCG and AFP
      during induction chemotherapy are inaccurate parameters for the prediction of
      treatment failure. In contrast, initial serum concentrations of HCG and AFP are
      highly significant in the prediction of unfavourable treatment outcome.

PMID- 9020491
TI  - Bcl-2 expression and response to chemotherapy in colorectal adenocarcinomas.
AB  - In the last year, a number of studies have reported the expression of bcl-2 in
      colorectal adenocarcinomas. However, the influence of bcl-2 expression on
      response to chemotherapy and outcome in patients with advanced colorectal
      adenocarcinoma has not been reported. We analysed bcl-2 expression in 231
      colorectal tumours from patients that were treated by surgery alone or with 5
      fluorouracil-based chemotherapy. Of 231 tumours, 149 (64.5%) overexpressed bcl-2.
      Bcl-2 expression was associated with low plasma CEA levels (P=0.013) and
      inversely associated with poor differentiation (P=0.049). However, bcl-2
      expression did not significantly influence failure-free or overall survival in
      surgically treated patients. In the group of patients receiving 5-fluorouracil
      based chemotherapy bcl-2 expression did not influence response to chemotherapy;
      nor did it effect failure-free or overall survival.

PMID- 9020493
TI  - Evaluation of visual inspection as a screening test for cervical cancer.
AB  - Visual inspection of the uterine cervix by paramedical personnel has been
      proposed for the early detection of cervical cancer, as an alternative to routine
      cytology screening in developing countries. We evaluated the performance of this
      procedure in detecting precursor lesions and cancer in a study involving 2843
      married women in Kerala, India. Two thresholds were used to define a positive
      test. In the lower one, any abnormality was considered as positive. The cut-off
      point for the high threshold was one or more of the high-risk findings: bleeding
      on touch, suspicious growth/ulcer and hard, irregular, oedematous cervix. A Pap
      smear was performed on all subjects, and a biopsy was done for those with
      moderate dysplasia and above. A combination of cytology and histology findings
      was used as the 'gold standard'. Using the low threshold, 1279 (45%) women were
      positive on visual inspection, and with the higher threshold 179 (6.3%) were
      positive. There were six moderate dysplasias, nine severe dysplasias, ten
      carcinomas in situ and 13 invasive carcinomas. With the lower threshold,
      sensitivity and specificity to detect moderate dysplasia and above were 65.8% and
      55.3% respectively; the values for severe dysplasia and above were 71.9% and
      55.3% respectively and for invasive cancer were 92.3% and 55.2% respectively.
      With the higher threshold, the sensitivity decreased considerably (28.9% to
      detect moderate dysplasia lesions, 31.3% for severe dysplasia and 53.8% for
      clinical cancer) and the specificity increased to approximately 94%. At a lower
      threshold, the sensitivity was not satisfactory, and the test was highly non
      specific; at a higher threshold sensitivity was even lower. Thus, the test
      characteristics of visual inspection are not very promising either as a
      preselection procedure for cytology or as a low-technology measure for cervical
      cancer screening in developing countries.

PMID- 9020494
TI  - Body mass index and post-menopausal breast cancer: an age-specific analysis.
AB  - The relationship between body mass index (BMI, Quetelet's index, kg m(-2)) and
      post-menopausal breast cancer risk was considered in age-specific strata on the
      basis of a pooled analysis of three Italian case-control studies, including a
      total of 3108 post-menopausal breast cancer patients aged 50 years or over and
      2664 control subjects. Overall, there was a moderate, but significant,
      association between BMI and post-menopausal breast cancer: the odds ratios (ORs)
      were around 1.3 for the three intermediate quintiles compared with the lowest
      one, and 1.4 for the highest one. The association was moderate among women aged
      50-59 years and 60-69 years, with ORs around 1.3 for the highest BMI quintiles,
      but stronger among elderly women, with ORs of 1.6 for the fourth and 2.1 for the
      fifth quintile. An 8-unit increase in BMI involved an OR of 1.18 at age 50-59
      years, of 1.14 at age 60-69 years and of 1.59 above age 70 years. This pattern of
      risk is similar to that observed for post-menopausal hormone replacement
      treatment and is consistent with a duration-risk relationship in the exposure to
      high oestrogen levels and with a greater differential in oestrogen levels in
      overweight elderly women. In terms of population attributable risk, 19.6% of all
      post-menopausal breast cancer patients and 27.1% of those in women above age 70
      years were attributable to overweight and obesity in this population. This has,
      therefore, major preventive implications as to reduce breast cancer risk late in
      life, it is essentially important to control weight gain in elderly women.

PMID- 9020495
TI  - Prevalence of cancer in the elderly: discrepancies between self-reported and
      registry data.
AB  - Data on self-reported cancer by a sample of 3349 elderly persons in the south
      west of France were validated against registry data in the same region: only 21%
      of the persons on the cancer registry reported occurrence of cancer. Breast
      cancer was found to be most frequently accurately reported.

PMID- 9020496
TI  - Validation of an algorithm able to differentiate small-cell lung cancer (SCLC)
      from non-small-cell lung cancer (NSCLC) patients by means of a tumour marker
      panel: analysis of the errors.
AB  - By means of a mathematical score previously generated by discriminant analysis on
      90 lung cancer patients, a new and larger group of 261 subjects [209 with non
      small-cell lung cancer (NSCLC) and 52 with small-cell lung cancer (SCLC)] was
      analysed to confirm the ability of the method to distinguish between these two
      types of cancers. The score, which included the serum neuron-specific enolase
      (NSE) and CYFRA-21.1 levels, permitted correct classification of 93% of the
      patients. When the misclassifications were analysed in detail, the most frequent
      errors were associated with limited disease SCLC with low NSE levels and with
      advanced NSCLC with high NSE levels. This demonstrates the importance of the
      marker in correctly categorizing patients.

PMID- 9020497
TI  - Parental cancer and risk of papillary and follicular thyroid carcinoma.
AB  - In a population-based case-control study in the Uppsala-Orebro Health Care Region
      of Sweden, the histories of cancer among parents of 517 histologically confirmed
      cases of papillary and follicular carcinoma and of a similar number of sex- and
      age-matched controls were compared. The parental history of cancer was compiled
      through information from death certificates and from the nationwide Cancer
      Register. The incidence of malignancies in a cohort of parents of cases of
      thyroid cancer was also compared with the incidence in the whole Swedish
      population. A maternal history of cancer was more common among women with
      follicular carcinoma than among their controls (OR 2.11, 95% CI 0.96-4.67).
      Parents of probands with papillary carcinoma had an increased risk of thyroid
      cancer (OR 4.25, 95% CI 1.16-10.89), and mothers of probands with follicular
      carcinoma had an increased risk of stomach cancer (OR 3.65, 95% CI 0.99-9.35)
      compared with the general population. Cancer of the lung, breast, and pancreas
      were less common than in the general population. Familial cases of thyroid cancer
      were not limited to the papillary type. An inheritable pattern of carcinogenesis
      is possible for certain differentiated non-medullary thyroid cancers, but shared
      environmental exposures may also explain the parent-child associations of cancer
      in this study.

PMID- 9020498
TI  - Clustering of childhood leukaemia in Hong Kong: association with the childhood
      peak and common acute lymphoblastic leukaemia and with population mixing.
AB  - Incidence data of childhood leukaemia (CL) in Hong Kong (1984-90) have been
      analysed for evidence of variation between small areas. All cases (n=261) were
      classified by morphological cell type, with the majority (n=205) being acute
      lymphoblastic leukaemia (ALL), and haematological review has permitted
      immunophenotypic classification for 73% of these. The data have been examined for
      evidence of spatial clustering within small census areas (TPUs) and for
      association with population mixing, with attention focused on those subgroups
      (especially the childhood peak of ALL--taken here to be diagnoses in children
      from 24 months up to the seventh birthday--and common ALL) which, it has been
      hypothesized, may be caused by unusual patterns of exposure and response to
      common infections. For the whole of Hong Kong, there was evidence of spatial
      clustering of ALL at ages 0-4 years (P = 0.09) and in the childhood peak
      (P<0.05). When these analyses were restricted to TPUs where extreme population
      mixing may have occurred, overall incidence was elevated and significant evidence
      of clustering was found for ALL (P<0.007) at these ages and for the common ALL in
      the childhood peak (P = 0.032). Replication of the analyses for subsets of
      leukaemia that were not dominated by the childhood peak of ALL found no evidence
      of clustering. This is the first investigation of an association between
      population mixing and childhood leukaemia in Asia and the first to include
      clustering and to consider particular subsets. The results are supportive of the
      'infectious' aetiology hypothesis for subsets of childhood leukaemia,
      specifically common ALL in the childhood peak.

PMID- 9020499
TI  - 'Tumour volume'.

PMID- 9020501
TI  - The effect of age on aluminum retention in rats.
AB  - The present study was designed to assess potential changes in aluminum (Al)
      retention during advanced age. Young (21 day old), adult (8 months), and old (16
      months) rats were exposed to 0, 50, and 100 mg Al/kg/day administered as aluminum
      nitrate in drinking water for a period of 6.5 months. Urinary Al levels were
      measured after 3 and 6.5 months of Al exposure. Organ weights and tissue Al
      concentrations were examined at 6.5 months of Al administration. Differences in
      the tissue accumulation of Al with age included higher liver, kidneys, spleen,
      bone and testes levels in old rats than in tissues of both young or adult
      animals. In contrast, brain concentrations were higher in young rats. Urinary Al
      levels of young, adult or old Al-exposed rats showed different trends at 6.5
      months of Al exposure: compared with young values adult values declined, while
      those of old rats tended to increase further. The current results show that
      tissue Al retention patterns may be significantly altered depending on the age at
      Al exposure. This finding may be of concern for future investigations on the
      potential role of Al in certain neurological disorders.

PMID- 9020500
TI  - High-dose 5-fluorouracil infusional therapy is associated with hyperammonaemia,
      lactic acidosis and encephalopathy.

PMID- 9020502
TI  - Cytokines (IL-1beta and TNFalpha) in relation to biochemical and immunological
      effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats.
AB  - Previous studies in different strains of rats and mice have shown that the
      inhibition of gluconeogenesis as a result of reduced liver phosphoenolpyruvate
      carboxykinase (PEPCK) activity together with appetite suppression play critical
      roles in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent
      immunological studies in rats demonstrated that exposure to low doses of TCDD
      resulted in an early and enhanced IgG response to immunization with sheep red
      blood cells (SRBC) and an enhanced delayed-type hypersensitivity (DTH) reaction
      as well as a positive popliteal lymph node (PLN) response. However, high doses of
      TCDD suppressed the DTH reaction. This study aimed at examining the involvement
      of cytokines (IL-1 and TNF) in mediating the above effects. Liver samples from a
      previous dose-response study on DTH reaction were investigated, in which rats
      were treated with TCDD (1, 3, 10, 30 and 90 microg/kg) and immunized with an
      antigen. mRNA levels of IL-1beta were elevated begining at the 1 microg/kg (non
      lethal) dosage group with a maximum increase of about 5-fold above controls in
      the 90 microg/kg (lethal) dosage group. mRNA levels of TNFalpha were also
      significantly elevated begining at the 30 microg/kg dosage group. These results
      suggest that at low doses of TCDD, increased IL-1beta could be responsible for
      immune function stimulation, whereas at high doses of TCDD, greatly elevated
      TNFalpha and IL-1beta levles may exacerbate or mediate acute toxicity including
      immune suppression and related biochemical effects. A time course study (60
      microg TCDD/kg without immunization) revealed that liver mRNA levels of TNFalpha
      were significantly elevated starting 24 h, and reaching a maximum 48 h after
      dosing with TCDD. This change was accompanied by a transient increase of mRNA
      levels of IL-1beta at day 4 after TCDD dosage. Thus, these data demonstrated that
      TCDD alone (without immunization) can cause transient increases of mRNA levels of
      TNFalpha and IL-1beta in liver. Results from these experiments suggest that TCDD
      induced cytokine changes may play important roles in various effects of TCDD.

PMID- 9020503
TI  - Role of tachykinins and neutral endopeptidase in toluene diisocyanate-induced
      bronchial hyperresponsiveness in guinea pigs.
AB  - The role of tachykinins in toluene diisocyanate (TDI)-induced non-specific
      bronchial hyperreactivity (NSBH) in guinea pigs was investigated, and it was
      determined whether or not the activity of airway neutral endopeptidase (NEP) was
      inhibited in conditions where a bronchial hyperreactivity to acetylcholine (ACh)
      was observed. Exposures to 3 ppm TDI for 1 h, or to 0.029 ppm for 8 weeks caused
      a significant bronchial hyperreactivity to ACh. The depletion of tachykinins by a
      pretreatment with capsaicin (140 mg/kg) eliminated the TDI-induced airway
      hyperresponsiveness in both patterns of exposure to TDI. Capsaicin treatment had
      no effect on the response to ACh in guinea-pigs exposed to air (controls).
      Bronchial NEP activity determined by histoenzymology was significantly less 4 and
      24 h after the end of a 1-h exposure to 3 ppm TDI than after exposure to air.
      Bronchial NEP activity evaluated 24 h after the end of a 48-h exposure to 0.116
      ppm TDI, or a 1-week exposure to 0.050 ppm TDI was not significantly different
      from those of controls exposed to air, whereas in the same conditions of exposure
      a NSBH is observed in guinea-pigs. These data suggest that tachykinins released
      from C-fibers upon acute or repeated exposures to high or low concentrations of
      TDI, respectively, play an essential role in the observed bronchial
      hyperreactivity, and that the inhibition of NEP by TDI cannot completely account
      for the observed airway hyperreactivity.

PMID- 9020504
TI  - Enhancement of the stress response by minute amounts of cadmium in sensitized
      Reuber H35 hepatoma cells.
AB  - The aim of this study was to determine whether the cadmium-induced cellular
      stress response can be modulated by the subsequent application of low
      concentrations of the same ion. It is shown that exposure of Reuber H35 rat
      hepatoma cells to cadmium concentrations of 10 or 30 microM for 1 h leads to a
      biphasic change in their sensitivity towards a second exposure to cadmium, an
      initial sensitization is followed by development of tolerance towards the
      secondary treatment with cadmium. Furthermore, incubations for 1 h in the
      presence of 10 microM of cadmium induce the synthesis of the major heat shock
      proteins except for hsp60. A step-down cadmium regime, i.e. a pretreatment of 1 h
      with 10 or 30 microM immediately followed by incubations with lower
      concentrations of cadmium (ranging from 0.03 to 1 microM), leads to additional
      increases in hsp synthesis. Since no effect of these low concentrations was
      observed on hsp synthesis in non-pretreated cells, the effect of a step-down
      treatment thus results in a higher effect on hsp synthesis than could be expected
      based on their summation. The sensitized cells also develop a higher level of
      tolerance in the presence of the above mentioned low concentrations of cadmium.
      It can be concluded that during the transient period of enhanced sensitivity, low
      concentrations of the original stressor enhance the synthesis of hsps and thus
      induce higher levels of tolerance in comparison with cells which only received
      the primary cadmium treatment.

PMID- 9020505
TI  - Long-term exposure of male and female mice to trivalent and hexavalent chromium
      compounds: effect on fertility.
AB  - Sexually mature male and female mice at 50 days of age were exposed to trivalent
      (Chromium chloride) or hexavalent (potassium dichromate) chromium compounds in
      drinking water for 12 weeks. The effects of the direct chromium exposure on
      fertility was assessed at day 140 of age. Fertility was significantly reduced in
      males exposed to the trivalent chromium compound. The number of implantation
      sites and the number of viable fetuses was significantly reduced in females
      impregnated by males exposed to the hexavalent chromium compound. The number of
      resorptions and dead fetuses was increased in females impregnated by males
      exposed to trivalent and hexavalent chromium compounds. The exposure of female
      mice to trivalent and hexavalent chromium compounds significantly reduced the
      number of implantation sites and the number of viable fetuses. The number of
      females with resorptions was significantly increased in hexavalent chromium
      exposed females. The number of resorptions was increased in trivalent and
      hexavalent exposed females. Body, seminal vesicles and preputial gland weights
      were significantly reduced in males exposed to trivalent and hexavalent chromium,
      whereas testes weight was significantly increased in males exposed to these
      compounds. Furthermore, ovarian weight was significantly increased in females
      exposed to trivalent and hexavalent chromium, whereas uterine weight was
      significantly decreased in trivalent chromium exposed females. In conclusion, the
      ingestion of trivalent and hexavalent chromium compounds by adult male and female
      mice would cause adverse effects on fertility and reproduction.

PMID- 9020506
TI  - Inhibition of DNA synthesis by paracetamol in different tissues of the rat in
      vivo.
AB  - DNA synthesis in the spleen, testis, thymus, stomach, small intestine and bone
      marrow was inhibited by 70-90% at 1 h following an oral dose of paracetamol (1
      g/kg). This inhibitory effect was still apparent using a lower dose of 125 mg/kg
      paracetamol, but not when the dose was reduced to 60 mg/kg. In contrast, the
      liver was resistant to the inhibitory action of paracetamol on DNA synthesis,
      there being no significant inhibition of DNA synthesis at 500 mg/kg or 1 g/kg
      paracetamol. These doses and the associated plasma levels are in the range found
      in human overdose. Tissue levels of paracetamol in the liver, spleen, thymus,
      kidney and testis were essentially the same as the plasma level. However the
      apparent paracetamol tissue levels in the stomach wall and duodenum were orders
      of a magnitude higher than the plasma level. The tissue levels of paracetamol did
      not explain the differences between tissues in the degree of inhibition of DNA
      synthesis, in particular the high levels of paracetamol in the tissue of the
      stomach and duodenum did not result in higher levels of inhibition in these
      tissues. This study also shows that the inhibitory effect of paracetamol on DNA
      synthesis is transient. All the tissues, except the spleen, no longer showed
      inhibition of DNA synthesis by 4 h post paracetamol dosing.

PMID- 9020507
TI  - Effects of arsenite pretreatment on the acute toxicity of parathion.
AB  - Parathion (PA) is a phosphorotioate pesticide requiring P-450-mediated oxidations
      to become activated to paraoxon, or to be metabolised to its less toxic
      metabolites. On the other hand, sodium arsenite [As(III)] markedly decreases
      total hepatic P-450 content and dependent monoxygenase activities. Our aim was to
      determine the effects of As(III) pretreatment on the acute toxicity of PA and its
      possible relationship with the effects of As(III) on P-450-dependent
      monooxygenase activities. Adult male Wistar rats were pretreated with As(III)
      (5.6 mg As(III)/kg, s.c.), and 24 h later given PA (5 to 20 mg/kg, per os).
      As(III) pretreatment increased the acute toxicity of PA, reducing 38% its median
      lethal dose (LD50) from 11.68 to 7.21 mg PA/kg. In addition, As(III) pretreatment
      further decreased the inhibitory effect of PA on brain acetylcholinesterase
      activity, reducing 33% the median inhibitory dose (ID50) from 3.44 to 2.31 mg
      PA/kg. whereas As(III) alone had no significant effects. As(III) decreased the P
      450 content to 87% of control values, reduced EROD activity to 74% and BROD
      activity to 41%; PA produced no significant effects on these parameters, whereas
      the joint administration of As(III)+ PA produced effects similar to those of
      As(III). PROD activity was reduced to 36% of control value by PA, whereas As(III)
      alone produced no significant effects. However, As(III) pretreatment apparently
      protected against the inhibition of CYP2B1-mediated PROD activity produced by PA,
      since PROD values were similar to those of control animals. Our results also
      indicated that the increase in PA toxicity caused by As(III) pretreatment, could
      also be related to the CYP2B2 isoform, since decreases in CYP2B2-dependent BROD
      activity were observed in both As(III) and As(III) + PA groups, but not in PA
      treated animals, suggesting that CYP2B2 is involved in PA detoxification.

PMID- 9020508
TI  - Utilization of renal slices to evaluate the efficacy of chelating agents for
      removing mercury from the kidney.
AB  - Mercury is an environmental contaminant that preferentially accumulates in the
      kidney. It has been previously shown using proton-induced X-ray emission analysis
      that mercury (HgCl2) accumulated in precision-cut rabbit renal cortical slices.
      In this study, the efficacy of seven chelating agents for the removal of Hg from
      renal slices has been examined. Rabbits were injected with HgCl2 (10 mg/kg) and 3
      h later kidneys were sliced, or renal slices were exposed in vitro to a mildly
      toxic concentration of HgCl2 (5 x 10(-5)M, 4 h). The slices were then treated in
      vitro with 10 mM concentrations of EDTA, lipoic acid (LA), penicillamine (PA),
      glutathione (GSH), 1,4-dithiothreitol (DTT), DMSA, or DMPS. DMPS proved to be the
      most effective in mobilizing Hg from in vivo or in vitro HgCl2-exposed renal
      tissue ( > 85% of control after 3 h incubation). Relative efficacies for the
      seven agents were DMPS > DMSA, PA > DTT, GSH > LA, EDTA. The use of renal slices
      appears to be a useful in vitro tool for assessing the efficacy of chelating
      agents on mobilizing accumulated Hg from renal tissue.

PMID- 9020509
TI  - Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate
      oligonucleotides, following subacute intradermal administration in Sprague-Dawley
      rats.
AB  - The systemic toxicity of two phosphorothioate oligonucleotides specific for
      herpes simplex viruses (ISIS 1082) and human papiloma virus (ISIS 2105) were
      evaluated following repeated intradermal injections of vehicle control, 0.33,
      2.17, or 21.7 mg/kg daily to Sprague-Dawley rats (10/sex/group) for 14 days.
      Animals were sacrificed 1 day after the last dose, except for a portion of the
      ISIS 1082-treated animals (5/sex/group) which were maintained for an additional
      14-day recovery period. The profile of alterations noted for both compounds was
      very similar. Other than local signs of irritation at the site of injection,
      there were no clinical signs of toxicity or treatment-related mortality, but
      there was a slight decrease in body weight gain for the 21.7 mg/kg dose groups.
      Alterations in hematology parameters included dose-dependent thrombocytopenia and
      anemia. Alterations in serum chemistry parameters were suggestive of mild
      alterations in hepatic metabolism, with increases in liver transaminases and
      bilirubin, along with decreases in albumin and cholesterol. Both spleen and liver
      weights were significantly elevated in a dose-dependent fashion.
      Histopathological alterations noted in liver, kidney, lung, injection site skin,
      and spleen were characterized as perivascular and interstitial infiltrates of
      macrophages and monocytes. Additional microscopic alterations in the spleen
      included mild lymphoid hyperplasia (seen in lymph nodes as well), and
      extramedullary hematopoiesis. Treatment-related cytopenias were likely related to
      mild, focal hypocellularity in the bone marrow. Alterations in ISIS 1082-treated
      animals were only partially reversed following the 14-day treatment-free period.
      In conclusion, repeated intradermal administration of ISIS 1082 and ISIS 2105
      produced a similar spectrum of toxicities, with liver, kidney, spleen, and bone
      marrow being identified as target tissues.

PMID- 9020510
TI  - Sequence of exposure to cadmium and arsenic determines the extent of toxic
      effects in male Fischer rats.
AB  - Arsenic and cadmium are both priority hazardous substances and human carcinogens.
      Although there is the potential for simultaneous exposure to both metals, the
      interactions of cadmium and arsenic are not well defined. We examined the
      toxicity of these metals when given alone or in alternating sequence to adult
      male Fischer rats. In the first study, a non-toxic dose of arsenic (22.5 micromol
      NaAsO2/kg, s.c.) was given 24 h before cadmium (10, 20, or 30 micromol CdCl2/kg,
      s.c.) and toxicity was assessed 24 h later. Arsenic pretreatment markedly reduced
      mortality in rats given the high dose of cadmium (9 survivors/10 treated)
      compared to rats given cadmium alone (2/10). Arsenic pretreatment also reduced
      cadmium-induced hepatotoxicity, as indicated by serum glutamic oxalacetic
      transaminase (SGOT) activity, and markedly reduced cadmium-induced testicular
      hemorrhagic necrosis. Arsenic pretreatment produced an 8-fold increase in hepatic
      levels of metallothionein (MT), a metal-binding protein often associated with
      cadmium tolerance. In the second study, a non-toxic dose of cadmium (3 micromol
      CdCl2/kg, s.c.) was given 24 h before arsenic (68, 79, 84, or 90 micro/mol
      NaAsO2/kg. s.c.) and toxicity was assessed 24 h later. Cadmium pretreatment did
      not alter the lethality of the high dose of arsenic and had no effect on arsenic
      induced hepatotoxicity. Although cadmium pretreatment had no effect on arsenic
      toxicity, it produced large increases in hepatic MT (26-fold) before the arsenic
      challenge and greatly enhanced MT induction after the challenge. Thus, even
      though both arsenic and cadmium induce MT synthesis, only arsenic pretreatment
      protects against cadmium intoxication, and cadmium pretreatment does not effect
      arsenic toxicity. Thus, toxic interactions of arsenic and cadmium appear to
      depend on the sequence of exposure.

PMID- 9020511
TI  - Effects of dithiocarbamates on toxicity of cadmium in rat primary hepatocyte
      cultures.
AB  - The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p
      hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the toxicity of Cd in
      the rat primary hepatocyte cultures were studied. Cytotoxicity was assessed by
      measuring cell viability, extra cellular lactic dehydrogenase (LDH) activity, and
      intracellular lipid peroxidation and active oxygen species. Primary hepatocyte
      cultures were treated with 109CdCl2 (5, 10 or 50 microM Cd and 1.7 KBq of
      109Cd/well) for 30 min or 4 h. BGD or HBGD was added to the culture medium to
      make the final concentration of 100 microM and incubated for 4.5 h in 30 min Cd
      exposure or 1 h in 4 h Cd exposure. Decreases in the hepatocyte viability caused
      by all Cd exposure concentrations were significantly prevented by treatment with
      BGD or HBGD. The treatment with the chelating agents for 4.5 h after Cd exposure
      for 30 min significantly prevented increases in extracellular LDH activity.
      Increases in the lipid peroxidation in hepatocytes exposed to Cd for 30 min or 4
      h were prevented significantly by treatment with BGD or HBGD for 4.5 h or 1 h,
      respectively. Moreover, the increases in the level of active oxygen species
      caused by Cd exposure for 30 min were significantly prevented by treatment with
      the chelating agents for 1.5 h. These findings suggest that BGD and HBGD protect
      against the cytotoxicity of Cd in rat primary hepatocyte cultures and that the
      protective effects of chelating agents presumably result from a decrease in the
      Cd level, the effective sequestration of the reactive Cd ion, and the direct
      preventive effect on the active oxygen species in the hepatocytes.

PMID- 9020512
TI  - The acute effect of lead acetate on glucocorticoid receptor binding in C6 glioma
      cells.
AB  - Lead exerts significant toxic effects on the nervous system, the hematopoietic
      system and the kidney. Specific cellular sites of action of this environmental
      pollutant have not been elucidated in the central nervous system. The present
      investigations were conducted to test the hypothesis that lead exposure perturbs
      glucocorticoid-mediated events in central nervous system hormonal target tissues.
      Utilizing the C6 glioma cell culture model in these studies, glucocorticoid
      receptor binding to its cytosolic receptor was investigated. Receptor binding
      studies yielded a Kd= 10.5 +/- 0.5 nM and a Bmax = 486 +/- 27 fmol/mg protein in
      untreated cells versus a Kd = 23.1 +/- 2.6 nM and Bmax = 472 +/- 35 fmol/mg
      protein in cells exposed to 10 microM lead acetate for 24 h. Presence of lead in
      these glial cells may decrease affinity of the glucocorticoid for its receptor
      without affecting receptor number. Treatment with 10 microM lead acetate for 48
      h, resulted in a significant reduction in glucocorticoid-regulated glycerol
      phosphate dehydrogenase (GPDH) specific activity. These effects were not due to
      cell cytotoxicity assessed as cell number growth curves, [3H]thymidine
      incorporation or trypan blue exclusion. In protein kinase C (PKC) activity
      assays, treatment of cells with sodium or lead acetate and dexamethasone
      indicated that both lead and dexamethasone affect the distribution of PKC. In
      lead-treated cells cytosolic PKC activity was reduced 48% when compared to sodium
      acetate treated controls. Taken together, these results suggest that acute
      exposure of C6 cells to lead may inhibit processes involved in glucocorticoid
      mediated signal transduction events within central nervous system hormonal target
      cells. Lead may perturb initial glucocorticoid binding events possibly by
      affecting PKC-mediated phosphorylations in the glucocorticoid signal transduction
      system.

PMID- 9020513
TI  - Comparative effects of essential and nonessential metals on preimplantation mouse
      embryo development in vitro.
AB  - It is well recognized that deficiencies of essential trace elements during early
      development can result in structural abnormalities and/or embryonic death.
      Recently, there has been increasing interest in the concept that small excesses
      of essential metals can also have negative effects on the developing embryo. We
      hypothesized that, with respect to toxicity, metals with similar physico-chemical
      properties would act by similar mechanisms to influence the preimplantation
      embryo. In the current study we investigated the influence of four essential (Cu,
      Mn, Fe, Zn), and eight nonessential (Cr, Hg, Pb, V, Al, Ag, Cd, As) metals on
      mouse preimplantation embryonic development. Two cell stage mouse embryos were
      cultured for 72 h in media containing varying metal concentrations (0.05 - 200
      microM). Embryo cell differentiation and proliferation were respectively assessed
      by scoring for blastocyst formation and final embryo cell number. Both
      nonessential and essential metals were embryotoxic at relatively low
      concentrations. However, in contrast to our expectations, at similar molar
      concentrations, redox active essential metals were less toxic than non-redox
      active nonessential metals. These data suggest that direct metal binding to
      critical membrane sites and/or intracellular ligands, including protein and
      nucleic acids, may trigger abnormal development and death prior to metal
      associated oxidative damage.

PMID- 9020514
TI  - Chronic exposure of rats to ozone and sulfuric acid aerosol: biochemical and
      structural responses.
AB  - Groups of rats were exposed to either 0.12 or 0.20 ppm of ozone, 20, 100, or 150
      ppm of sulfuric acid aerosol (0.4-0.8 microm diameter), or their mixtures in
      whole body exposure chambers for up to 90 days. Matched control animals were
      exposed to filtered air in comparable chambers. The rats were examined
      biochemically and morphometrically for centriacinar fibrosis or other indicators
      of pollutant-induced changes in the terminal bronchiole-alveolar duct junction
      region of the lung at the end of the exposures. By evaluating different markers
      of lung injury, we had previously demonstrated a synergistic interaction between
      ozone and sulfuric acid aerosol after acute exposures to these same
      concentrations of the pollutants. The present experiments were designed to answer
      the question of whether there was any interaction between ozone and respirable
      sized aerosols of sulfuric acid, synergistic or antagonistic, after chronic
      exposures. Exposure of rats to 0.12 or 0.20 ppm of ozone elicited tissue and
      cellular changes at the bronchiole-alveolar duct junction. Concurrent exposure to
      sulfuric acid aerosol did not affect the extent or magnitude of these changes.
      Intermittent exposure (12 h per day) to ozone, with or without the acid aerosol,
      elicited a greater response than did continuous exposure (24 h per day). No
      consistent effects of exposure to sulfuric acid aerosol alone were observed,
      either morphometrically or biochemically. The biochemical data were consistent
      with the morphometric analyses, showing trends towards or significantly increased
      lung 4-hydroxyproline content in the rats exposed to ozone, with or without
      sulfuric acid aerosol, in the intermittent exposure experiment, but not after
      continuous exposure. No interactive effects between ozone and sulfuric acid
      aerosol were observed with any of the biochemical parameters examined. We
      conclude that ozone and sulfuric acid aerosols do not exhibit synergistic
      interactions after chronic exposures (90 days) of rats to the concentrations
      tested in this study, which correspond to concentrations showing synergistic
      interactions in previously performed acute studies. We also observed that
      exposure of rats to ozone for 12 h per day elicited greater lung changes, which
      we interpret to indicate a mild fibrotic response, than did exposure of rats for
      24 h per day, whether or not there was accompanying exposure to the acid aerosol.

PMID- 9020515
TI  - Importance of cholinolytic drug selection for the efficacy of HI-6 against soman
      in rats.
AB  - The influence of cholinolytic drugs (atropine, benactyzine, biperiden) on the
      efficacy of the oxime HI-6 (1-[[[(4-aminocarbonyl)pyridinio]methoxy ]methyl]-2
      [hydroxyimino)methyl]pyridinium dichloride monohydrate) on soman-induced
      anticholinesterase and stressogenic effects was studied in rats. Soman-induced
      acetylcholinesterase inhibition in blood and diaphragm and the stressogenic
      effects of soman, i.e. an increase in plasma corticosterone level and liver
      tyrosine aminotransferase activity, were more significantly diminished by HI-6 in
      combination with benactyzine or biperiden in comparison with HI-6 plus atropine.
      These findings support a hypothesis that benactyzine as well as biperiden can
      increase the efficacy of the oxime HI-6 in comparison with atropine. They
      demonstrate the importance of cholinolytic drug selection in the treatment of
      soman poisoning in rats. Ltd.

PMID- 9020516
TI  - Structure-activity relationships in the hydrolysis of acrylate and methacrylate
      esters by carboxylesterase in vitro.
AB  - Acrylate esters are important chemicals in the plastics industry, whose toxicity
      is theorized to involve alkylation of critical cellular nucleophiles via the
      Michael addition. Carboxylesterase-mediated hydrolysis of acrylates may be a
      detoxification mechanism as the unsaturated acid produced is not electrophilic
      under physiological conditions. Using purified porcine liver carboxylesterase,
      the enzymatic hydrolysis of several acrylate esters was characterized to
      determine Km and Vmax values for each ester. The Km (microM) and Vmax (nmol/min)
      values observed for ethyl acrylate were 134 +/- 16 (S.D.) and 8.9 +/- 2.0,
      respectively. While the Km for ethyl methacrylate was not significantly
      different, the Vmax 5.5 +/- 2.5, was significantly lower compared with the
      corresponding value for ethyl acrylate. The Km and Vmax for butyl acrylate were
      33.3 +/- 8.5 microM and 1.49 +/- 0.83 nmol/min, respectively, and the
      corresponding values for its alpha-methyl analog were not significantly
      different. The Km and Vmax for tetraethyleneglycol dimethacrylate were 39 +/- 15
      microM and 2.9 +/- 1.0 nmol/min, respectively. The Vmax for ethyleneglycol
      dimethacrylate, 6.9 +/- 2.4 nmol/min, was significantly higher than that of the
      larger bifunctional ester tetraethyleneglycol dimethacrylate, but the Km was not
      significantly different. These results indicate that alpha-methyl substitution
      appears to have a minor effect in the enzymatic hydrolysis of acrylates, and
      suggest that the relative toxicity of acrylates is not due to differences in
      carboxylesterase-mediated hydrolysis.

PMID- 9020517
TI  - Prediction of teratogenic potency of valproate analogues using cerebellar
      aggregation cultures.
AB  - The aim of this study was to develop a novel in vitro system suitable for
      preclinical testing for developmental toxicity of drugs. An assay system
      consisting of primary cultures of dissociated cerebella from 6-day-old mice was
      chosen, since it allowed quantification of neuronal aggregation and fasciculated
      neurites. A human teratogen, the antiepileptic drug valproic acid (VPA), as well
      as its structural analogues, ( +/- )-4-en-VPA and E-2-en-VPA, with varying
      teratogenic activities, were tested and found to affect aggregation and fiber
      formation of cerebellar neurons. Based on a dose-response study, the
      concentrations of compounds causing 50%, inhibition (IC50) of formation of thick
      and thin fibers were determined. The lowest IC50 values were found for VPA (52 +/
      7 and 86 +/- 11 microM for thick and thin fibers, respectively), which in vivo
      caused the highest rate of exencephaly among the three compounds tested, ( +/- )
      4-en-VPA exhibited intermediate values (150 +/- 30 and 300 +/- 40 microM),
      whereas the highest IC50 values were found for E-2-en-VPA (260 +/- 42 and 430 +/-
      40 microM). The latter compound does not induce neural tube defects, but has been
      shown to have neurobehavioral effects in prenatally exposed animals.
      Subsequently, the purified S- and R-enantiomers of 4-yn-VPA (teratogenic and non
      teratogenic, respectively) were tested for their effects on aggregation and fiber
      formation of the cerebellar neurons. Treatment with S-4-yn-VPA resulted in
      pronounced changes in numbers of aggregates and fasciculated processes compared
      to the cultures treated with R-4-yn-VPA, indicating that the intrinsic
      stereoselective potency of the enantiomers may be correlated to the difference in
      their effects on cerebellar neurons in vitro. Thus, the teratogenic potency of
      VPA and its analogues correlated with their effects on aggregation of neural
      cells and formation of fasciculated neurites in primary cultures of dissociated
      cerebella, indicating that the in vitro assay system employed may be used as a
      pre-screening test for prediction of teratogenic potency of drugs.

PMID- 9020518
TI  - Selenite suppression of cadmium-induced testicular apoptosis.
AB  - The characteristic apoptotic ladder-like patterns of rat testicular DNA on
      agarose gel electrophoresis which results from treatment with CdCl2 are
      suppressed by the administration of Na2SeO3. The examination of testicular tissue
      using an ELISA programmed cell death detection procedure confirmed this selenite
      suppression of cadmium-induced apoptosis. The administration of the Na2SeO3 at
      either 0.5, 1, 2 h prior to or 0.5, 1, 2 h after the administration of the CdCl2
      appear to be almost equally effective at suppressing the apoptotic response.
      These results are in accord with previous studies on the Na2SeO3 suppression of
      cadmium induced necrotic changes in tissues and suggest that Na2SeO3 interferes
      with both necrosis and apoptosis.

PMID- 9020519
TI  - Protective effects of antioxidants against benomyl-induced lipid peroxidation and
      glutathione depletion in rats.
AB  - The present in vivo study was designed to examine the effects of the
      antioxidants, N,N-diphenyl-p-phenylenediamine (DPPD) and a 21-aminosteroid
      (U74389G), on methyl 1-(butylcarbamoyl)-2-benzimidazole-carbamate (benomyl)
      induced lipid peroxidation and glutathione depletion in rats. Male Sprague Dawley
      rats weighing 200 250 g were used in this study and were fasted for 8 12 h before
      treatment. Benomyl (200 mg/kg/day in olive oil) was administered orally for 7
      days to groups of untreated rats and to rats pretreated with two doses (15 mg/kg)
      of either DPPD or U74389G. Benomyl treatment resulted in a significant increase
      in serum hydroperoxides and a significant decline in hepatic reduced glutathione
      (GSH) levels. These results indicate that benomyl induces lipid peroxidation and
      glutathione depletion in rats. Benomyl-induced lipid peroxidation was blocked by
      DPPD pretreatment but was not significantly altered by U74389G. However, both
      antioxidants, DPPD and U74389G, were able to inhibit glutathione depletion
      induced by benomyl. The present findings indicate that the in vivo toxicity of
      benomyl may be associated with oxidative stress to cellular membranes and that
      some degree of protection against this toxicity could be afforded by
      antioxidants.

PMID- 9020520
TI  - Testosterone pretreatment mitigates cadmium toxicity in male C57 mice but not in
      C3H mice.
AB  - Previous work has indicated that testosterone pretreatment protects against
      cadmium-induced toxicity in male rats while other data indicate that pretreatment
      of mice with testosterone offers no such protection against cadmium. Since
      cadmium toxicity may vary widely with species and strain, we examined the effect
      of testosterone pretreatment on cadmium toxicity in two strains of mice, one that
      is sensitive (C3H) and one that is resistant (C57) to cadmium toxicity. A single
      sc injection of 20 micromol CdCl2/kg to C3H mice or 45 micromol CdCl2/kg to C57
      mice proved very toxic, causing 50%, and 44% mortalities, respectively. However,
      when C57 mice were pretreated with testosterone (5 mg/kg, s.c., at - 48, - 24,
      and 0 h) prior to cadmium (45 micromol/kg), complete resistance to cadmium
      induced lethality developed. Testosterone had no effect on cadmium-induced
      lethality in C3H mice. Testosterone prevented extensive hepatocellular damage
      caused by cadmium in C57 mice and also significantly reduced cadmium-induced
      elevations in serum lactate dehydrogenase (LDH) activity and blood urea nitrogen
      (BUN), which are indicators of hepatic and renal function, respectively. The
      toxicokinetics of cadmium were apparently not affected by testosterone
      pretreatment, as the distribution of cadmium to liver in either strain was
      unchanged by the steroid. Cadmium-induced metallothionein (MT) levels in liver
      and kidney of C57 mice were increased in testosterone-pretreated mice given the
      higher doses of metal but no such enhancement of MT synthesis occurred in C3H
      mice. This increase in MT may provide some level of protection against cadmium
      toxicity in the C57 mice. These results indicate that testosterone pretreatment
      prevents toxicity of cadmium in male C57 mice, possibly through enhancement of MT
      synthesis, but has no effect in male C3H mice.

PMID- 9020521
TI  - Significant suppression of rat liver aldolase B by a toxic coplanar
      polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl.
AB  - A toxic coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl
      (PenCB), significantly suppresses the expression of liver aldolase B in rats.
      Hepatic aldolase activity in PenCB-treated rats was significantly reduced to
      about 50% of that in free- and pair-fed control groups. The reduced aldolase
      activity following PenCB-treatment was due to the marked suppression of the
      expression of aldolase B shown by immunoblot analysis after SDS-polyacrylamide
      gel electrophoresis and two-dimensional gel electrophoresis. The suppression of
      rat liver aldolase B could be a key biochemical lesion caused by PenCB.

PMID- 9020522
TI  - Colchicine-induced elevation of tissue metallothionein contents is mediated by
      inflammation-independent serum factor.
AB  - Subcutaneous injection of colchicine caused dose-dependent and time-dependent
      induction of hepatic MT in mice. Other than colchicine, similar MT induction was
      observed in vincristine- or vinblastine-injected mice, but not in beta
      lumicolchicine-injected mice. MT contents were also elevated in the kidney,
      spleen, lung and heart by colchicine injection. Isoforms of colchicine-induced MT
      in the liver were identified to be MT-I and II by immunoblot analysis. Unlike
      turpentine-induced MT synthesis, dexamethasone, an anti-inflammatory agent, could
      not block the MT-inducing activity of colchicine. Therefore, the MT-inducing
      activity of colchicine does not appear to be due to inflammation. Mouse serum,
      obtained at 4-24 h after colchicine treatment, stimulated MT induction in rat
      hepatoma H4IIEC3 cells. The MT-inducing activity in the serum from colchicine
      treated mice was determined to be highest at 12 h after colchicine injection. The
      MT-inducing activity from sera of colchicine-treated mice was completely blocked
      by glucocorticoid antagonist, RU38486, similar to such activity in the serum from
      lipopolysaccharide-treated mice. The ability of sera to induce MT was abolished
      by heat treatment (56 degrees C, 30 min). The molecular weight of the MT-inducing
      factor estimated by gel filtration was approximately 20 000 Da. Thus, colchicine
      induced stimulation of MT production is mediated by some humoral factor. The
      production of the MT-inducing factor was not blocked by dexamethasone. We
      conclude that the mediator is not an inflammatory cytokine or a glucocorticoid
      and suspect that the disruption of microtubule triggers production or release of
      such humoral mediator which stimulates MT induction.

PMID- 9020523
TI  - The effects of cyclosporin A, dexamethasone and other immunomodulatory drugs on
      induced expression of IL-3, IL-4 and IL-8 mRNA in a human mast cell line.
AB  - We examined by RT-PCR the effect of a number of immunomodulatory compounds on
      cytokine gene expression at the level of mRNA in the HMC-1 human leukemic mast
      cell line. Resting cells expressed relatively low constitutive levels of mRNA for
      the cytokine genes IL-3, IL-4 and IL-8, and mRNA levels for each of these
      cytokines were significantly enhanced after 4-h stimulation with the calcium
      ionophore ionomycin. Treatment of the cells with the immunosuppressant CsA at 10(
      5) M produced a significant inhibition of ionomycin-induced expression of IL-3,
      IL-4 and IL-8 mRNA, and at 10(-6) M produced a significant inhibition of induced
      expression of IL-3 and IL-8 but not IL-4. At both concentrations of CsA,
      expression of IL-3 was inhibited to a greater extent than that of the other two
      cytokines. Treatment of the cells with the corticosteroid DEX at 10(-5) M but not
      10(-6) M significantly reduced the ionomycin-induced expression of IL-3 but not
      IL-4 or IL-8 mRNA. Progesterone and methotrexate were both inactive in modulation
      of induced cytokine expression in this cell line. In conclusion, this study shows
      that cytokine expression, particularly of IL-3, is inhibited in a human mast cell
      line by CsA and DEX. These findings may be relevant to the anti-allergic action
      of these drugs.

PMID- 9020524
TI  - Immunomodulatory and protective effects of N-acetylcysteine in mitogen-activated
      murine splenocytes in vitro.
AB  - N-Acetylcysteine (NAC) is a pro-glutathione drug used to treat chronic lung
      disorders and because of its anti-AIDS virus activity in vitro, has been proposed
      for AIDS therapy. The effect of NAC on mitogen-activated-lymphocyte blastogenesis
      in C57B1/6 mouse splenocytes and ability of NAC to protect lymphocytes against
      mitogen-induced cytotoxicity was examined in vitro. NAC increased splenocyte
      proliferation in the presence of optimal and suboptimal concentrations of
      concanavalin A (Con A) and lipopolysaccharide (LPS). Stimulatory and
      costimulatory effects of NAC on mitogen-induced responses were also evident. The
      dose-response relationship describing the effects of NAC on lymphocyte
      proliferation with Con A-induced responses were enhanced in a dose-dependent
      manner, whereas the corresponding LPS-induced responses increased to a maximum
      level followed by decline in responses at higher concentrations of NAC. When
      splenocytes were incubated with inhibitory supraoptimal concentrations of Con A
      (10 microg/ml) or LPS (150 microg/ml), NAC partially enhanced the Con A-induced
      response but completely prevented the inhibitory effect of supraoptimal
      concentrations of LPS on splenocyte blastogenesis. Optimal and supraoptimal
      concentrations of Con A caused activation-induced cell death in the splenocytes
      whereas comparable concentrations of LPS did not produce a similar effect.
      Splenocyte cell death produced by the optimal mitogenic concentrations of Con A
      was completely blocked by the addition of NAC to cultures. Immunomodulation and
      protective effects of NAC were observed in mitogen-activated lymphocytes in
      vitro.

PMID- 9020525
TI  - Inhalation of diesel exhaust enhances antigen-specific IgE antibody production in
      mice.
AB  - To examine the effects of diesel exhaust (DE) inhalation on IgE antibody
      production, BALB/c mice were exposed to 0 (control), 3.0 and 6.0 mg/m3 DE
      inhalation for 3 weeks. Intranasal sensitization with ovalbumin (OA) three times
      at intervals of 3 weeks was conducted immediately before, immediately after and 3
      weeks after DE inhalation. Body weight and thymus weight for the DE-exposed and
      control mice were essentially the same but spleen weight in mice exposed to 6
      mg/m3 significantly increased. Anti-OA IgE antibody titers in the sera of mice
      exposed to 6 mg/m3 was significantly higher than the control. Total IgE and anti
      OA IgG in sera for DE-exposed and control mice remained basically the same. To
      investigate cytokine production in mice exposed to 6 mg/m3, spleen cells from DE
      exposed and control mice were stimulated with OA in vitro and cytokine production
      in the culture supernatants was measured by ELISA. In vitro antigen-stimulated
      interleukin-4 (IL-4) and -10 (IL-10) production in spleen cells of exposed mice
      significantly increased compared to the control. In vitro interferon (IFN)-gamma
      production in spleen cells of exposed mice markedly decreased. DE inhalation is
      thus shown to have adverse effect on antigen-specific IgE antibody production in
      mice through alteration of the cytokine network.

PMID- 9020526
TI  - The role of prolidase as an enzyme participating in the metabolism of collagen.
AB  - Prolidase (E.C. 3.4.13.9) is a cytosolic exopeptidase that cleaves
      imidodipeptides and imidotripeptides with C-terminal proline or hydroxyproline.
      The enzyme apparently contributes to the conservation of iminoacids from
      endogenous and exogenous protein sources, mainly collagen. Prolidase plays an
      important role in the recycling of proline for collagen synthesis and cell growth
      and probably serves as an interface between protein nutrition and matrix
      breakdown. It seems that prolidase activity (despite the collagen gene
      expression) may be a step limiting factor in the regulation of collagen
      biosynthesis. The prolidase gene (PEPD) is located on chromosome 19 and encodes a
      polypeptide of 493 amino acids with molecular weight 54 kDa. The mature form of
      the enzyme is a dimer composed of two identical subunits. The gene harbors
      polymorphic alleles without effect on activity. Rare mutations found on exons
      7,8,12 and 14 may be responsible for prolidase deficiency. Prolidase deficiency
      is characterized by massive imidodipeptiduria, skin lesions, recurrent
      infections, mental retardation and elevated proline-containing dipeptides in
      plasma. An effective treatment of the disease has not been identified.

PMID- 9020527
TI  - Nitric oxide in learning and memory.
AB  - The role of nitric oxide in the central nervous system is described. The main
      part of this article concerns the problem of learning and memory.

PMID- 9020528
TI  - Clostridium difficile colitis--diagnosis and therapy.
AB  - Clostridium difficile is a Gram-positive bacillus which had been identified as
      the source of potent exotoxins: toxin A and toxin B. C. difficile infection
      usually follows antibiotic therapy and results from unrestrained growth of
      pathogenic strains of C. difficile in the colon. Typical clinical findings
      include: diarrhoea with blood and mucus, fever, abdominal pain, nausea, loss of
      body weight. In the past the diagnosis was based on positive result of stool
      culture but now several tests are available: latex-agglutination test, enzyme
      immunoassays and fluorescence-immunoenzymatic tests. Diagnostic methods enable
      quick and safe detection of C. difficile antigens or toxins and proper
      management. Poor susceptibility of C. difficile strains to common antibiotics
      hinders choosing the effective therapy.

PMID- 9020529
TI  - The effect of pentagastrin, cholecystokinin and their analogues on rat arterial
      blood pressure and isolated heart.
AB  - The influence of pentagastrin (PG) and its analogues: 3-leupentagastrin (3-leu
      PG), 4-AspOBzl-pentagastrin (4-AspOBzl-PG), and of the cholecystokinin -terminal
      tetrapeptide (CCK-4) and its analogue CCK-4(Phet) on rat arterial blood pressure
      and isolated heart were studied. 4-AspOBzl-PG and CCK-4 (Phet) had no effect on
      the arterial blood pressure or the isolated heart. PG (1.0 microgram/kg iv),
      slightly raised the systolic and diastolic arterial blood pressure, whereas 3-leu
      PG (1.0 microgram/kg iv) slightly lowered the systolic arterial blood pressure. 3
      leu-PG (0.1 microgram/0.1 ml), like PG (0.1 microgram/ 0.1 ml) increased the
      contraction amplitude of the isolated heart and had no effect on the heart rate,
      but unlike PG, it had no effect on coronary outflow. CCK-4 (1.0 microgram/kg iv)
      slightly raised the systolic arterial blood pressure but, unlike cholecystokinin
      had no effect on the isolated heart. We conclude that shortening of the CCK chain
      to a C-terminal tetrapeptide reduces the positive inotropic effect. Blocking of
      one of the aspartic acid carboxyl groups by a benzyl radical in the 4 PG position
      eliminates the PG effect on the circulatory system. Substitution of metionine for
      leucine at the 3-PG position reduces the PG action on the circulatory system.

PMID- 9020530
TI  - Behavioural activity of angiotensin II (3-7)4Phe--analogue of natural fragment 3
      7 of angiotensin II.
AB  - A study was made of the influence of pentapeptide 3-7 angiotensin II [AII(3-7)],
      its analogue 3-7(4)Phe [AII(3-7)4Phe] and angiotensin II (AII) on the behaviour
      of adult male rats. The motility, stereotypy, spatial performance, learning of
      conditioned and passive avoidance responses allowing to avoid aversive
      stimulation were estimated. Examined peptides at the dose 1 nmol injected
      intracerebroventricularly 15 min before the experiment did not produce specific
      changes in psychomotor activity in the "open field" test and in retention of the
      spatial task in the Morris water maze. The rate of acquisition of conditioned
      avoidance responses was stimulated by AII(3-7)4Phe, AII(3-7) and AII
      administration. In the passive avoidance situation AII improved retention of the
      responses whereas analogue AII(3-7)4Phe and fragment 3-7 caused similar though
      less pronounced effect. All the peptides applied immediately before the
      experiment intensified stereotypy, a behaviour evoked by of apomorphine-1 mg/kg
      and amphetamine-7.5 mg/kg intraperitonealy injection. These results show similar
      psychotropic activity of analogue AII(3-7)4Phe, comparable with the activity of
      natural fragment 3-7 of angiotensin II.

PMID- 9020531
TI  - The nitrate and nitrite contents in a whole day's hospital diet during the spring
      season.
AB  - It was decided to evaluate the exposition of patients on nitrates and nitrites
      contained in 6 whole day's standard hospital diets taken in various days. Studies
      were performed in June 1995. It was found that the mean daily intake of nitrates
      was 311 mg and the mean intake of nitrites were 2.16 mg per patient. The main
      source of nitrates were vegetables (85%), whereas the main source of nitrites
      were meat and meat-containing products. The presented results suggest that the
      diets containing early vegetables (especially cabbage) may be harmful for human
      health.

PMID- 9020532
TI  - Diagnosis and surgical treatment of pancreatic carcinoma.
AB  - The aim of study was presentation of our experiences in diagnosis and treatment
      in pancreatic carcinoma in confrontation with current opinions. Between 1984-1995
      at our Department was treated 211 patients with carcinoma of exocrine part of the
      pancreas. It were 137 male and 74 female with mean age 58.9 years. In 151 cases
      (70.5%) primary seat of tumour was located in the head and in 60 cases (29.5.1%)
      in the body or tail of pancreas. The diagnosis was determined on the basis of
      clinical symptoms and laboratory investigation Diagnostic accuracy of X-ray
      investigations was as follow: Ultrasonography-86%, CT-scan-91%, ERCP-94%.
      Ultrasonography or CT guided biopsy and serodiagnosis improved detectability of
      resectionable carcinomas in the last past years. Among 211 patients, 199
      underwent surgery. The procedures depended on the localisation and grade of
      advance of the tumours. UICC classification of pancreatic tumours, pTNM (4th
      edition 1987) was used. Only in 21 patients (9.9%) (tumours pT1a-b N0M0) was
      possible to perform radical operation (resection of the pancreas). However in 107
      patients (50.7%) were done only paliative procedures (pT2N1M0). In 83 patients
      (39.3%) only laparotomy and biopsy were performed (tumours pT2N1M1). The study
      shows that although improvement of the diagnostic methods tumors of the pancreas
      are diagnosed in stages making unable the radical procedures and only about 10%
      of carcinomas are resectable. It is relevant with non-characteristic picture of
      the diseases in its early stages.

PMID- 9020533
TI  - Chronic advanced pancreatitis--diagnosis, biochemical and ultrastructural changes
      and surgical procedures.
AB  - On the basis of 162 cases of chronic advanced pancreatitis seen at our Department
      during the last 15 years the diagnosis, indications and surgical procedures are
      described in this paper. Quantitative and qualitative changes of pancreatic
      collagen in chronic inflammation were also analysed. Results of these
      investigations were compared with histological and ultrastructural pictures of
      pancreatic tissue. Amongst 162 patients, 142 (88%) were operated upon. 71
      underwent pancreatectomy or pancreatoduodenectomy, 14 anastomotic procedures and
      rest of them various operation of the bile ducts. Overall, 18 (13%) patients
      experienced significant complications after resectional procedures and 6 (4%)
      died as well after anastomotic procedures.

PMID- 9020534
TI  - Morphological and histochemical changes in the liver of albino Wistar rat given
      flupenthixol depot.
AB  - Histological findings and histoenzymatic reactions have shown that Flupenthixol
      Depot (FPX dep.) injected to rats in therapeutic doses induced morphologically
      observable degenerative lesions in the liver. No significant difference in the
      intensity of the lesions between the groups of male and female animals was found.

PMID- 9020535
TI  - Delayed-type hypersensitivity skin reaction estimated with Multitest CMI in human
      giardiasis.
AB  - Delayed-type hypersensitivity skin reaction performed with Multitest CMI as an
      indicator of cell-mediated immunity, has been evaluated among 20 adults with
      giardiasis. There were no correlation found between Multitest CMI score and
      clinical course of the disease, but significant correlation was observed in
      relation to CD4/CD8 ratio, an another indicator of cell-mediated immunity.
      Multitest CMI score revealed lower values in giardiasis patients than in
      controls, and it was associated with significantly higher frequency of hypoergic
      reactions among subjects.

PMID- 9020536
TI  - Aquatic fungi of the Narew River and its tributaries in the stretch from
      Siemianowka to Doktorce.
AB  - The work was undertaken to investigate the mycoflora of the lowland river Narew
      and its tributaries in the stretch from Siemianowka to Doktorce. Samples of water
      collected once a month over the years 1987-1991 for hydrochemical analysis and
      studies of the stretch from Siemianowka to Doktorce. The following fungi unknown
      from Poland were found in this rivers: Dangeardia laevis. Lagenidium
      rabenhorstii, Olpidiopsis achlyae, Phytophthora megasperma, Phytophthora
      gonapodyoides, Pythium akanense, Tricladium fuscum and Tricladium patulum.

PMID- 9020537
TI  - Does anti-parasitic treatment normalize platelets morphology in patients infested
      with Entamoeba histolytica?
AB  - Platelets are part of body defence system, especially the anti-parasite
      immunologic response. Platelets manifest their functions only after their
      activation. Thrombine activates platelets inducing change of their shape and
      causing secretion of certain substances. This study was designed to estimate
      platelet morphology as an indicator of their activation and effectiveness of anti
      parasite therapy. The study was conducted in group of 30 patients infested with
      E. histolytica before treatment (A) and group of 23 patients after 2-week
      treatment course (B). The diagnosis of amoebiasis was based on detection of cyst
      forms in faeces. During the course of amoebiasis increase of platelets count and
      platelet crit (PCT) was observed. Mean platelet volume (MPV) in both groups (A
      and B) was decreased as compared with control group. We suggest that E.
      histolytica activates platelets, and the degree of their activation determines
      their morphologic parameters, and these changes come back to normal values during
      anti-parasite treatment.

PMID- 9020538
TI  - Human serum alcohol dehydrogenase isoenzymes as a markers of liver injury during
      viral hepatitis.
AB  - We examined the activity of class I and II of alcohol dehydrogenase isoenzymes in
      the sera of patients with viral hepatitis using fluorogenic substrates, 4-methoxy
      1-naphthaldehyde for class I and 6-methoxy-2-naphthaldehyde for class II. It was
      found that serum activities of class I and II of alcohol dehydrogenase isoenzymes
      during five weeks of hospitalisation were higher than that of control. The
      greatest increase in activities was found at the onset of disease, and exceeded
      the mean control value about 30 times for class I and 4 times for class II. These
      were lower than the aminotransferase activities but higher than the activity of
      lactate dehydrogenase, alkaline phosphatase and gamma-glutamyltransferase. In the
      following periods of investigation the activity of alcohol dehydrogenase
      isoenzymes gradually decreased, but did not reach the values of the control
      groups in the last period of the study. Activity of class I and II of alcohol
      dehydrogenase isoenzymes showed a good correlation with alanine and aspartate
      aminotransferase and lactate dehydrogenase in the first weeks of the illness.
      These results clearly demonstrate that particularly the activity of class I of
      alcohol dehydrogenase isoenzymes measured by a fluorimetric method can be a
      useful marker of liver cell damage in the course of viral hepatitis.

PMID- 9020539
TI  - DNA locus HLA-DQ alpha polymorphism in human population of the north-eastern
      Poland.
AB  - Investigations on DNA polymorphism locus HLA-DQ alpha were carried out on a
      sample of 117 adult unrelated inhabitants from the north-eastern Poland. The
      polymerase chain reaction and the reverse dot-blot hybridisation were employed to
      detect 6 different HLA-DQ alpha alleles. Population data on 20 different
      genotypes served as a basis for statistic evaluation. The results of genotype
      analysis were in Hardy-Weinberg equilibrium. Other population data were compared.

PMID- 9020540
TI  - Is wheat germ agglutinin (WGA) a glycosylated protein?
AB  - Lectin isolated from wheat germ was purified by affinity chromatography on ovogel
      column, recrystallization and gel filtration on Ultrogel AcA 44 column, eluted
      with borate buffer to eliminate accidental lectin-ligand interaction products. In
      87-times purified WGA preparation fucose, xylose, mannose, galactose and glucose
      were found, amounting 1.5% of lectin mass.

PMID- 9020541
TI  - Synthetic analogues of netropsin and distamycin. III. Synthesis of a pyridine
      analogue of the pyrrolecarboxamide antitumour antibiotics.
AB  - The synthesis of a new pyridine analogue of netropsin, N,N'-bis[6-(N-3
      dimethylaminopropyl) carbamoylpyridin-2-yl] pyridine-2,5-dicarboxamide (VII) is
      described. The potential for use of VII as a carrier to place chemical
      functionalities into the minor groove of DNA which are capable of modifying DNA
      is discussed.

PMID- 9020542
TI  - Nucleotide-sugar binding to ribosomes. Comparison of affinity and capacity of
      gastric mucosa and liver ribosomes to sugar-nucleotides.
AB  - Highly purified ribosomes from gastric mucosa and liver were isolated and tested
      for their affinity and capacity toward UDP- monosaccharide binding. Ribosomes
      from both tissues bind UDP-N-acetylglucosamine nearly at the same level with
      similar affinity, but binding capacity of gastric ribosomes to UDP-N
      acetylgalactosamine was twice higher than in case of liver ribosomes, and with
      higher affinity than in case of UDP-N-acetylglucosamine. The binding of UDP-N
      acetylgalactosamine to mucosa ribosomes requires the whole sugar-nucleotide
      structure.

PMID- 9020543
TI  - Human population genetics of the VNTR locus D1S80 in the north-eastern Poland.
AB  - Population genetic studies within VNTR locus D1S80 were carried out on a
      population sample from the north-eastern Poland. DNA extraction was performed
      using the Chelex method. DNA amplification was followed by high-resolution PAGE
      and silver staining (AMP-FLP technique). In 116 unrelated individuals 20 alleles
      were observed. The D1S80 locus demonstrated a heterozygosity of 0.85. Comparison
      of the observable allele frequencies with population data from other Caucasian
      populations revealed no significant differences.

PMID- 9020544
TI  - Synthetic C-nucleosides. I. Synthesis and the anomeric configuration of 1,2,3
      triazole analogues of C-nucleosides.
AB  - Two 1,2,3-triazole analogues of C-nucleosides IV and V have been synthesized. The
      anomeric configuration of these nucleosides were established from 13C NMR spectra
      by using the own method.

PMID- 9020545
TI  - 5'-Nucleotidase and adenosine deaminase activities in hypertrophied rat heart.
      The effect of tachycardia.
AB  - Activity of 5'-nucleotidase (5NT) and adenosine deaminase (ADA) in the left heart
      ventricle was examined at normal heart rate and after atrial pacing in six weeks
      after constriction of the aorta above or below the renal vessels and in sham
      operated rats. The aorta constriction above the vessels reduced activity of 5NT
      by 29% and increased activity of ADA by 33%, whereas the constriction below the
      vessels resulted in elevated activity of both enzymes: 5NT by 16% and ADA by 145%
      at normal heart rate. The atrial pacing reduced 5NT activity and did not affect
      ADA activity in control rats and in those with constriction of the aorta below
      the vessels. The activity of both enzymes increased after constriction of the
      aorta above the renal vessels. It is concluded that adenosine metabolism in the
      hypertrophied heart may be changed due to changes in its production and
      degradation. Renin-angiotensin-aldosterone system seems to be involved in
      regulation of the activities of adenosine metabolizing enzymes in the
      hypertrophied heart.

PMID- 9020546
TI  - Activity of enzymes of various subcellular localisation in cytosol obtained after
      cell organelle precipitation at pH 5.0.
AB  - Acidification to pH 5.0 of various organ homogenates prepared in 0.25 M sucrose
      causes aggregation of cell organelles. Aggregated organelles are removed through
      standard centrifugation. Cytosol obtained reveals only slight activity of
      membrane and lysosomal enzymes. The cytosol is useful for evaluation of changes
      in enzyme distribution in cell.

PMID- 9020547
TI  - The effect of a herbicide--sodium salt of 2,4-dichlorophenoxyacetic acid on
      guerin carcinoma.
AB  - The effect of sodium salt of 2,4-dichlorophenoxyacetic acid, being an active
      component of herbicide "PIELIK", upon the development of Guerin carcinoma
      implanted in male Wistar rats, was studied. 192 animals were divided in to 6
      equal groups: I-animals which obtained physiological salt solution; II-rats
      exposed to the herbicide in postlactational period; III-animals with Guerin
      carcinoma, non exposed to the herbicide; IV- rats exposed to the herbicide in
      postlactational period+Guerin carcinoma; V-animals exposed to the herbicide from
      prenatal period to the end of an experiment, without Guerin carcinoma; VI-the
      same as in V group, but with Guerin carcinoma. The effect of the herbicide on
      tumor growth dynamism (diameters and mass), degree of tumour malignancy
      (metastases to lymph nodes), animals survival time and morfological changes in
      the primary tumour and in metastases was evaluated. Basing of the results
      obtained, it was stated that this herbicide accelerates the development of Guerin
      carcinoma and reduces the survival time in the rats exposed to it in the prenatal
      and postnatal period. However, it does not significantly influence the growth of
      the carcinoma in the rats exposed only in the postlactational period.

PMID- 9020548
TI  - The time course of ultrastructural changes in the secretory components of
      pancreatic acinar cells and trypsinogen activation in taurocholate pancreatitis
      in rats.
AB  - The purpose of this study was to compare a time course of ultrastructural changes
      of secretory compartment of acinar cells in the pancreas, and a pattern of
      trypsinogen activation during the course of taurocholate acute pancreatitis (AP)
      in rats. Acute pancreatitis was induced in 21 rats by injection 0.2 ml of 5%
      natrium taurocholate into the biliopancreatic duct. Control rats (n = 18) were
      sham operated (SO). The ultrastructural and biochemical (trypsinogen activation,
      free active [FAT] and total potential trypsin [TPT]) examinations were performed
      after 6, 12 and 18 h of AP or SO. Ultrastructural lesions of acinar cells
      comprised of disorganization of RER, enlargement of Golgi apparatus, changes in
      size, shape and number of zymogen granules. These alterations were most
      conspicuous after 6 h of AP and they were associated with maximal activation of
      trypsinogen. Biochemical changes gradually normalized at 12 to 18 h of AP,
      however the morphological lesions persisted at these intervals of time.

PMID- 9020549
TI  - Activity alterations of chosen parameters of cord blood hemostasis in newborns
      from complicated pregnancies with premature ablation of placenta.
AB  - The study was carried out on 20 newborns with diagnosed premature ablation of
      placenta of 0,I,II clinical degree. In comparison to healthy newborns (n = 30)
      statistically significant differences were proved in: ATIII activity-48% (65%),
      plasminogen concentration-50% (63%), alpha 2antyplasmin activity 53% (67%);
      euglobulin clot fibrinolysis time 70 (95) min., and fibrinogen concentration 1.4
      (1.8) g/l. The presented differences prove increased coagulation system
      activation in newborns from mothers with symptoms of premature ablation of
      placenta. Activity changes of hemostasis system in cases of premature ablation of
      placenta have the features of disorders accompanying intrauterine fetal anoxia.

PMID- 9020550
TI  - Epidemiological and clinical aspects of acute hepatitis C in north-eastern
      Poland.
AB  - The availability of more reliable assays made infections caused by hepatitis C
      virus (HCV) emerging as an extremely common and insidiously progressive disease.
      Since 1993, in 51 out of 798 patients admitted to Department of Infectious
      Diseases with acute hepatitis, HCV was diagnosed as a causative agent. Seventy
      one percent of acute hepatitis C cases were hospital associated and city
      residents represented the majority of all cases. The epidemiological data and
      clinical course of acute hepatitis C was analysed and compared with acute
      hepatitis B. The frequency of acute hepatitis C increased during last 3 years in
      Bialystok region. The clinical course of acute hepatitis C was generally milder
      than acute hepatitis B, with lower aminotransferases activities and bilirubin
      level.

PMID- 9020551
TI  - Neurohistochemical evaluation of adrenergic innervation in fetal development of
      the white rat.
AB  - Physiological development of adrenergic innervation, an important component of
      trophic and homeostatic regulation in the mammals was estimated. Our research is
      directed to evaluate both exo- and endogenous factors contributing to its
      impairment. The present investigation was carried out on 32 rat fetuses from
      three various 7-day periods of gestation. Histochemical studies included
      reactions to catecholamines according to Falck and Owman, and silver staining
      with AgNO3 according to the Bielschowsky-Gros method. Adrenergic innervation was
      examined in all fetal body regions, with a special reference to the pelvis.
      Catecholamines distribution and accumulation in plexuses, ganglia, neurons and
      chromatophilic cells, as well as serotonine content in mast cells were analyzed.
      It was found that in the initial period of gestation noradrenaline is absent. In
      the third week of gestation, the neurotransmitter's accumulation takes place to
      subsequently decrease gradually until the end of gestation. From this stage
      synaptic connections of adrenergic innervation with chromatophilic and mast cells
      could be detected.

PMID- 9020552
TI  - Decreased antioxidant status and increased lipid peroxidation in rats after
      methanol intoxication.
AB  - The liver is the main metabolic place where the methanol is oxidized to
      formaldehyde and to formate. The aim of this paper was to study the liver
      antioxidant system in acute methanol intoxication, after 6, 12, 24 hours and 2, 5
      and 7 days of alcohol administration into rats. In liver homogenates the
      superoxide dismutase, catalase, peroxidase and reductase glutathione activity and
      content of malondialydehyde (MDA), SH-compounds in protein and non-protein
      fraction and ascorbate were estimated. Activity of superoxide dismutase and
      catalase was significantly increased after 6 hours following methanol ingestion
      and persisted up to 2-5 days of intoxication. It was accompanied by significant
      decreased of reductase and peroxidase glutathione activities. The protein and non
      protein SH-groups were significantly decreased during 6 hours to 5 days following
      methanol ingestion. The liver MDA content was considerably increased. After 2
      days since methanol intoxication the liver vitamin C content was significantly
      decreased in comparison with the control group. The obtain results demonstrated
      that during methanol induced liver injury there are increase of lipid
      peroxidation and impairment of proantioxidant equilibrium in favour to
      prooxidant.

PMID- 9020553
TI  - Glyoxalase I (GLO I, EC 4.4.1.5) polymorphism in hemolysates and bloodstains.
AB  - Electrophoretic patterns of glyoxalase I (GLO I) phenotypes were evaluated in
      hemolysates and simulated case bloodstains in relation to duration and conditions
      of storage and type of substrate. The bloodstains deposited on different
      substrates were exposed to temperatures -20 degrees C, 4 degrees C, 18 degrees C,
      37 degrees C and 56 degrees C. Rapid decrease in the enzyme activity was found in
      the conditions of high temperature. Character of the substrate noticeably
      affected GLO I detectability.

PMID- 9020554
TI  - Influence of dipeptide derivatives of S-substituted cysteines on the time of
      fibrinolysis.
AB  - Amino acids containing sulphur, dipeptide derivatives of methionine and S
      substituted derivatives of cysteine are potent antifibrinolytic agents. The
      structural moiety of the substances responsible for the effect on the clot
      formation is not known. Present study was undertaken in order to evaluate the
      effect of some analogues of dipeptides containing S-substituted derivatives of
      cysteine with the formula A-Cys(S-X)-Y (where A-amino acid, X-benzyl, butyl,
      hexyl, nonyl and Y-OH or OMe) on clot dissolution under the antifibrinolytic test
      conditions. It has been found that dipeptide derivatives of S-substituted
      cysteine (except benzyl derivative) at low concentration evoke antifibrynolytic
      activity, while at high concentration they prevent clot formation. The results
      suggest that antifibrinolytic activity of tested compounds at low concentration
      may be due to the formation of antifibrinolitycally active conformation, while
      high concentration overcome the effect.

PMID- 9020555
TI  - Kallikrein-kinin system in patients with neoplastic diseases.
AB  - The concentrations of kininogens, prokallikrein, fibrinogen, plasma protein,
      proteinase inhibitor antigens, and the kininase, fibrinolytic and antipapain
      activities in plasma of 29 patients with various tumours (lung cancers,
      lymphomas, and others) during chemotherapy were measured. The same studies were
      performed on blood plasma of female patients operated on because of cervical or
      endometrial carcinoma (37 subjects) and submitted to subsequent local
      radiotherapy (before and after radiotherapy). A weak activation of kallikrein
      kinin system and significant decrease in kininase and fibrinolytic activities
      were found in those patients. It may suggest a role of bradykinin in prevention
      of therapy-induced hypercoagulability in patients with neoplastic diseases.

PMID- 9020556
TI  - Synthetic C-nucleosides. II. Synthesis of a 3-pyrrolecarboxamide analogue of the
      C-nucleoside.

PMID- 9020557
TI  - The effect of local radiotherapy on kallikrein activity in saliva secreted by
      parotid gland in patients with head and neck cancers.
AB  - The samples of parotid gland saliva, collected from control human subjects and
      those taken from patients with head and neck cancers were submitted to the assay
      of protein concentration and kininogenase and amidolytic kallikrein activities.
      No patients with parotid gland tumours were included. The effect of pilocarpine
      stimulation on these parameters was studied. It was found that the saliva
      secreted by parotid gland of the investigated patients contains less protein and
      lower kininogenase activity in comparison to control subjects. Pilocarpine
      administration resulted in an increase of protein concentration and a decrease of
      kallikrein activity both in control and investigated subjects. Radiotherapy did
      not evoke any significant changes in spontaneously secreted saliva. The
      radiotherapy resulted in a progressive decrease of protein concentration and
      kallikrein activity in saliva secreted by pilocarpine stimulated glands. The
      kallikrein activity per mg of protein contained in spontaneously secreted saliva
      increased significantly during radiotherapy but it distinctly decreased in the
      saliva of pilocarpine-treated patients. It allows to conclude that the parotid
      glands do not lose their ability to synthesize and secrete kallikrein during
      radiotherapy of head and neck cancers.

PMID- 9020558
TI  - Free fatty acids and triacylglycerol concentrations in the gastrointestinal
      mucosa of fasted-refed rats.
AB  - The aim of the study was to determine the free fatty acids and triacylglycerol
      concentrations in the gastric, duodenal, ileal and colonic mucosa of fasted-refed
      rats. As compared to fasted group, refeeding resulted in a significant increase
      of free fatty acids content in the mucosa of the stomach, ileum, and colon but
      not in the duodenum, while triacylglycerol concentration increased at that time
      only in the duodenum; in parallel with the mucosal lipid changes, it was observed
      a significant decline in plasma free fatty acids level. We suggest that plasma
      free fatty acids may be implicated in the formation of lipid balance during
      refeeding in the gastrointestinal mucosa.

PMID- 9020559
TI  - Influence of environmental factors on development of Bialystok newborns born in
      1987.

PMID- 9020560
TI  - The role of monocytes in the platelet release of von Willebrand factor.
AB  - Circulating blood monocytes, which are a source of foam cells contribute to the
      vascular lesions. Von Willebrand factor (vWF) is an adhesive multimeric
      glycoprotein that is synthesized only by endothelial cells and megakaryocytes. In
      the present study we assessed the ability of human platelets to secrete vWF after
      incubation with blood monocytes in vitro. Monocytes derived from blood of healthy
      adults were cultured and next incubated with washed platelets. von Willebrand
      factor antigen (vWF:Ag) was measured in the supernatant by Laurell
      immunoelectrophoresis. The study showed that Triton X-100 treated platelets
      released 82-112% of vWF:Ag. The levels of vWF:Ag in the supernatant with
      untreated platelets and incubated with monocytes without LPS were respectively 36
      48% and 45-72%. After incubation washed platelets with LPS stimulated monocytes a
      significant decrease in vWF:Ag level was observed (7-11%).

PMID- 9020561
TI  - The effect of X-radiation on the hypothalamo-hypophyseal neurosecretory system of
      the rat.
AB  - The aim of the study was to reveal alterations in the macrocellular
      neurosecretory system of the rat which occur under the influence of X-radiation.
      The experiment was carried out on 15 male Wistar rats, divided into 1 control and
      4 experimental groups. The animals were subjected to total-body-X-irradiation in
      a dose of 300R. Brains and cerebral pituitaries were collected after decapitation
      and fixed in Bouine's fluid. Staining with haematoxylin & eosin and paraldehyde
      fuchsin was applied. A reduction in the neurosecrete content was found after 7
      days following irradiation both in the area of perikarya and nerve processes of
      SON and PVN. In animals dissected on the 14th and 21st day following irradiation,
      a shift of neurosecrete along the neurosecretory path was observed (via nerve
      processes to the posterior lobe of cerebral pituitary). On the 28th day, the
      morphological picture of the system examined was similar to the control one. The
      above results indicate that initially X-radiation causes a decrease in the
      production of neurosecrete within SON and PVN; later, however, the amount of
      neurosecrete is increased, like in control nuclei.

PMID- 9020562
TI  - Assessment of beta-2-microglobulin concentration in serum and urine in rheumatoid
      arthritis.
AB  - Assessment of beta-2-microglobulin (beta-2-M) concentration in serum and urine
      was made in 50 patients with rheumatoid arthritis (RA). The most often noticed
      pathology was proteinuria. We observed a significant increase of beta-2-M
      concentration in serum of patients without rheumatoid factor and in patients with
      proteinuria. In all patients the concentration of beta-2-M in urine was
      significantly higher than in the controls. We did not observe any influence after
      treatment on beta-2-M concentration. The increase of the concentration of beta-2
      M may be a marker for the early damage of kidney in RA.

PMID- 9020563
TI  - The activity of alpha-amylase and its salivary isoenzymes in serum and urine of
      patients with neoplastic diseases of female reproductive organs.
AB  - The activities of alpha-amylase and its salivary isoenzymes were evaluated in
      serum and urine of 59 patients with ovary cancer, 10 women with endometrial
      carcinoma, 30 patients with cervical carcinoma and 20 women with other
      (nonmalignant) diseases of females reproductive system. An increased activity of
      alpha-amylase in serum was found in 39% of patients with ovarium carcinoma and in
      23% of patients with cervical carcinoma. The activity of salivary alpha-amylase
      in serum was elevated in 89% of patients with ovary carcinoma and in 63% of
      patients with cervical carcinoma and in 20% of patients with endometrial
      carcinoma. Serum and urine of women with nonneoplastic diseases of reproductive
      system demonstrates normal values of salivary alpha-amylase activity. These
      observations allow to conclude that the assay of salivary alpha-amylase may be
      useful as an additional index in diagnostics of ovary and cervical carcinomas.

PMID- 9020564
TI  - Focal solitary hypoechoic area in hepatic fatty infiltration: a cause of hepatic
      pseudomass in ultrasound examination.
AB  - A unusual pattern of hepatic fatty infiltration was detected sonographically in
      43 patients over a 2-year period. At appropriate gain settings and time gain
      compensations, the liver parenchyma demonstrated diffuse increased echogenicity
      except for a solitary hypoechoic area with relatively distinct margins, usually
      locate in the medial segment of the left hepatic lobe or right lobe in
      pericholecystic, perivascular or subcapsular locations. This hypoechoic focus
      varied in size between 15 and 50 mm and was typically ovoid, but was occasionally
      spherical or irregular in shape. Fourteen patients with such skip area underwent
      percutaneous needle biopsy because of concern that there was a space-occupying
      mass. Microscopic examination of specimens from the hypoechoic region revealed
      normal hepatic parenchymal cells, while tissue samples from the surrounding liver
      had high fat levels. In the remaining 29 patients, correlative radiologic studies
      supported the diagnosis of fatty liver and excluded a central-mass lesion. A
      localized area of normal hepatic tissue should be considered among the possible
      hypoechoic periportal area demonstrated within a fatty liver.

PMID- 9020565
TI  - Surgical treatment of prolapse of the rectum--evaluation of distant results.
AB  - In the years 1972-1995 41 patients suffering from prolapse of the rectum were
      operated according to the Moore method. The method is based on the observations
      which suggest that the cause of prolapse is intestinal intussusception which can
      be prevented by translocating the anus under the pubic joint. The observation
      time is from 1 to 23 years. Two patients were reoperated; one-as a result of a
      recurrence of rectal prolapse and one due to a post-operative adhesive ileus. One
      patient died as result of peritonitis following an overlooked microperforation in
      the rectal wall. In the case of the remaining patients, the treatment was fully
      successful. Regular defecation cycle as well as incontination of stool and flatus
      returned and the anal sphincters almost fully regained their tension in
      comparison to the pre-operative state. Early and distant results of surgery of
      prolapse of the rectum are satisfactory.

PMID- 9020566
TI  - Preliminary study on the effect of the selected calmodulin antagonists on the
      skin.
AB  - The aim of the study was to make a selection of the calmodulin antagonists, which
      could be useful in topical treatment of psoriasis. Four drugs were assessed:
      chlorpromazine, trifluoperazine, miconazole and ketoconazole. They were applied
      on the skin of guinea pigs, twice a day for the period of two weeks. Biopsy
      specimens from these sites were being taken for light microscopy, histoenzymatic
      examination and for evaluation of the proliferation activity of the epidermis
      (the AgNOR stain, after Ploton). A decrease in reaction activities for lactate
      dehydrogenase and succinic dehydrogenase as well as in the proliferation activity
      of the epidermis, could suggest an inhibitory effect of chlorpromazine and
      miconazole on the cell cycle and keratinization process.

PMID- 9020568
TI  - Autoantibodies--what do they recognize?

PMID- 9020567
TI  - Rudolf-Virchow-Preis 1996. Priestragerrede. Detection of surfactant protein gene
      expression by reverse transcriptase-polymerase chain reaction (RT-PCR) identifies
      metastases and occult tumor spread of pulmonary adenocarcinomas.
AB  - A highly sensitive assay using RT-PCR and primers specific for surfactant protein
      A (SP-A), B (SP-B), C (SP-C) and D (SP-D) genes was applied to detect nodal
      metastases and occult tumor spread of pulmonary adenocarcinomas. Transcripts of a
      367-bp long SP-B gene fragment were detected in all control lymph nodes and
      tonsils offering evidence of illegitimate transcription of the SP-B gene in cells
      of lymphatic tissue. SP-A, SP-C, and/or SP-D transcripts were detected in 30
      (83.3%) of 36 lymph nodes with histologically identifiable metastases of
      pulmonary adenocarcinomas and in 10 (55.5%) of 18 lymph nodes that were tumor
      free on histologic examination. These findings provide evidence of occult tumor
      spread in regionary lymph nodes which remains undetectable by conventional light
      microscopy but can be detected by RT-PCR. Gene expression of SP-A and SP-C was
      restricted to pulmonary adenocarcinomas but SP-D gene activity has been detected
      in pulmonary large cell carcinomas, one pulmonary adenosquamous carcinomas and in
      non-pulmonary adenocarcinomas as well.

PMID- 9020569
TI  - Myasthenia gravis.
AB  - Myasthenia gravis (MG) is the classical organ specific, autoantibody mediated and
      T cell dependent human autoimmune disease. It is almost invariably associated
      with pathological alterations of the thymus. These are described here with
      reference to distinct models of autoimmunization against the acetylcholine
      receptor (AChR). In MG with thymitis B cells are increased in the medulla forming
      germinal centers or diffuse B cell infiltrates. Intrathymic production of AChR
      specific autoantibodies is the result of a classical antigen-driven immune
      reaction that occurs completely inside the thymus and involves AChR on myoid
      cells as the triggering (myasthenogenic) antigen. In thymomas no intratumorous
      immune reaction occurs and the AChR is not the myasthenogenic antigen. Instead,
      an abnormal neurofilament that shares epitopes with the AChR is expressed in
      thymomas and may trigger AChR-specific, non-tolerogenic T cell selection by
      molecular mimicry. These data support the hypothesis that initial steps in the
      pathogenesis of MG take place within abnormal thymic microenvironments, be they
      inflammatory or neoplastic. The etiology of MG remains enigmatic.

PMID- 9020570
TI  - Autoimmunity and B-cell malignancies.
AB  - There is evidence indicating that autoreactive B cells constitute a substantial
      part of the B-cell repertoire. This autoreactive repertoire secrete the so called
      natural autoantibodies characterized by their broad reactivity mainly directed
      against very well conserved public epitopes. They fulfill the definition of an
      autoantibody since they are self-reactive, but they are not self-specific. As
      yet, NAA directed against determinants of polymorphism have not been reported.
      Their germinal origin is suggested by their early appearance during ontogeny,
      their expression of cross-reactive idiotopes and structural studies of their
      sequence. As for the physiological role of the repertoire, we can assume that it
      may play a major role as a first barrier of defense. It is presently unknown
      whether these polyreactive B cells could constitute a pre-immune template which
      through an antigen driven process may be involved in the production of immune
      high affinity antibodies. This autoreactive B cell repertoire frequently
      undergoes malignant transformation, although there is controversy concerning the
      reasons accounting for this. It has been postulated that the continuous challenge
      of this autoreactive repertoire by self-antigens could create propitious
      conditions for malignant transformation to occur. However, it can be
      alternatively postulated, that overexpression of certain genes reflect what
      happens during ontogeny, since V genes expression is a developmentally regulated
      phenomenon and not all V genes are expressed during fetal life. Some of the genes
      that are recurrently expressed by these malignancies are also over-expressed in
      fetal repertoires and even in the adult normal B cell repertoire. We do not know
      whether it is the challenge by self-antigens or whether alternatively this over
      expression simply reflects what happens with the fetal repertoire which could
      have selective advantages for malignization.

PMID- 9020571
TI  - Autoantigen receptors in extranodal non-Hodgkin B-cell lymphomas.
AB  - Extranodal lymphomas of B-cell origin show a biologic behavior different from
      nodal lymphomas and an unexplained preference of a specific histologic type, the
      so called MALT-type. The lymphoma cells of this type show specific colonization
      of lymphoid follicle centers and subepithelial plasma cell differentiation
      suggesting that the tumor is immunologically responsive in vivo to as yet
      unidentified signals. Their tumor immunoglobulin has been shown to recognize
      autoantigens but lacks reactivity with bacterial antigens. Recent studies provide
      certain evidence, that antigen may play a role in the pathogenesis of gastric
      MALT-type lymphoma. The malignant B cells responded to antigen-triggering in
      vitro and have undergone somatic hypermutation probably in response to antigen
      selection. Therefore it is possible, that the local stimulation of lymphoma
      precursor B-cells triggered either by exogenous (e.g. Helicobacter pylori) or
      endogenous (e.g. autoantigen) antigen in co-operation with the reactive
      inflammatory infiltrates establishes the local tumor growth until further
      mutagenic alterations guide tumor development and progression.

PMID- 9020572
TI  - Murine autoimmune gastritis and the gastric H,K-ATPase: insights from a new model
      and autoantibody detection system.
AB  - Human type A chronic gastritis or autoimmune gastritis (AIG) is associated with
      gastric H,K-ATPase-specific autoantibodies (HKAb). The pathogenic role of the
      HKAb and the triggering autoantigen(s) are unknown. In a mouse model, neonatal
      thymectomy (nTx) induces AIG, which is likely T cell mediated, although HKAb are
      always present. Our aim is to study the role of the H,K-ATPase in the initiation
      of AIG. The direct involvement of the H,K-ATPase in the onset of AIG is suggested
      by the following findings. AIG appears at the age of 1 month in susceptible
      BALB.D2 mice, i.e. the time at which H,K-ATPase expression reaches adult levels.
      A new HKAb assay system based on immunoprecipitation of native H,K-ATPase
      expressed in Xenopus oocytes has revealed that the early lesion is already
      associated with low titers of HKAb. Injection of gastric membranes, rich in H,K
      ATPase, into neonatal BALB.D2 mice without adjuvant induces a persisting AIG.
      This new model for AIG will provide the means to identify which H,K-ATPase
      subunit triggers AIG.

PMID- 9020573
TI  - The pathophysiology of spinal cord injury and its clinical implications.
AB  - The pathophysiology of spinal cord injury can be categorized as acute impact or
      compression. Acute impact injury is a concussion of the spinal cord. This type of
      injury initiates a cascade of events focused in the gray matter, and results in
      hemorrhagic necrosis. The initiating event is a hypoperfusion of the gray matter.
      Increases in intracellular calcium and reperfusion injury play key roles in
      cellular injury, and occur early after injury. The extent of necrosis is
      contingent on the amount of initial force of trauma, but also involves
      concomitant compression, perfusion pressures and blood flow, and administration
      of pharmacological agents. Preventing or quelling this cascade of events must
      involve mechanisms occurring in the initial stages. Spinal cord compression
      occurs when a mass impinges on the spinal cord causing increased parenchymal
      pressure. The tissue response is gliosis, demyelination, and axonal loss. This
      occurs in the white matter, whereas gray matter structures are preserved. Rapid
      or a critical degree of compression will result in collapse of the venous side of
      the microvasculature, resulting in vasogenic edema. Vasogenic edema exacerbates
      parenchymal pressure, and may lead to rapid progression of disfunction. Treatment
      of compression should focus on removal of the offending mass.

PMID- 9020574
TI  - Medical care of the neurosurgical patient.
AB  - Proper medical care before and after surgery play an important role in the
      overall care of patients requiring neurosurgery and will have an impact on the
      neurological recovery. Prevention of spinal cord destruction resulting from the
      cascade of events which occur secondary to central nervous system trauma is a
      critical part of a patient's preoperative care. High doses of methylprednisolone
      sodium succinate given within the first 8 hours of trauma are currently
      recommended to provide protection to neural tissue after trauma. Other promising
      drugs for patients with spinal trauma, such as 21-aminosteroids and GM-1
      gangliosides, may become available in the near future. Knowledge of potential
      complications after surgery and methods to prevent complications from occurring
      is an important part of the postoperative care of neurosurgical patients. This
      includes management of micturition and defecation dysfunction, management of
      postoperative pain, physical therapy to speed recovery, and providing good
      supportive care to the recumbent patient.

PMID- 9020575
TI  - Identification and management of brain tumors.
AB  - Brain tumors occur commonly in small animals. The clinical history and physical
      examination findings can strongly suggest their presence. Specifically, an older
      dog with onset of seizures and behavioral changes, or an older cat with
      behavioural changes and weakness, should be further evaluated for the presence of
      a brain tumor. A thorough neurological examination should be performed to
      localize the lesion(s). Groups of neurological signs will suggest the tumor to be
      cerebral, cerebellar, or brainstem. Cerebral tumors without brainstem signs carry
      the best prognosis, especially for cats. Patients suspected of having brain
      tumors should be imaged with computed tomography, or magnetic resonance imaging.
      Initial medical therapy includes anticonvulsants and glucocorticosteroids.
      Cerebral tumors not located on the floor of the calvarium can be successfully
      excised. These and other tumors can also be treated with radiation therapy.

PMID- 9020576
TI  - Surgical conditions of the cervical spine.
AB  - This article reviews the four most common surgical conditions of the cervical
      spinal cord other than vertebral fractures including atlantoaxial instability,
      cervical disc disease, caudal cervical spondylomyelopathy, and spinal cord
      tumors. Each disease is reviewed by signalment, history, neurological
      examination, differential diagnosis, pertinent diagnostic testing, treatment,
      postoperative care, and prognosis.

PMID- 9020577
TI  - Conditions of the thoracolumbar spine.
AB  - Neurological deficits suggesting trauma to the spinal cord in the thoracolumbar
      area are the most common clinical presentation of neurosurgical conditions. By
      far, the most common cause of thoracolumbar spinal cord dysfunction is
      intervertebral disc disease. Disc herniation and subsequent spinal cord
      compression usually requires prompt medical treatment, then referral for high
      detail radiographs, myelogram, and surgical decompression. Other causes of
      thoracolumbar spinal cord dysfunction include neoplasia, discospondylitis,
      fibrocartilaginous embolism, and degenerative myelopathy.

PMID- 9020578
TI  - Conditions of the lumbosacral spinal cord and cauda equina.
AB  - Lumbosacral conditions are now recognized as compromising a significant
      percentage of problems for dogs and cats with rear limb abnormalities. Diagnosis
      is based on logically ruling out the more common maladies and then performing
      specific diagnostic procedures that definitively show the lesion(s).

PMID- 9020579
TI  - Principles of vertebral fracture management.
AB  - Traumatic disruption of the spine and supporting soft tissue structures may
      result in vertebral fracture or luxation and subsequent spinal cord compromise.
      An understanding of the regional anatomy is important to the discussion of
      pathophysiology and treatment of traumatic disorders. Various traumatic forces
      result in disruption of specific anatomic structures and reflect inherent
      stability or instability of the vertebral column. The neurological examination,
      and sequential neurological examinations, reflect the degree of spinal cord
      damage and vertebral instability. Patients in whom radiographs show instability,
      have severe neurological signs or worsening neurological signs, should be treated
      surgically. Several spinal stabilization techniques are available and their
      choice is contingent on the location in the spinal column, size of the patient,
      and the surgeon's experience. The prognosis is determined primarily by the
      severity of neurological signs, and the stability of the fixation technique.

PMID- 9020580
TI  - Peripheral nerve injury.
AB  - Inadequate peripheral nerve regeneration as a result of trauma contributes
      greatly to the morbidity of surgical patients. Animals admitted as an emergency
      often have concurrent orthopaedic injuries that impair mobility and may mask
      peripheral nerve dysfunction if a thorough neurological examination is not
      performed. This article reviews the pertinent anatomy of the peripheral nervous
      system as well as the degenerative and regenerative responses that occur in
      traumatized nerves. Physical examination and electrodiagnostic techniques that
      characterize the extent of nerve impairment are described. The management of
      peripheral nerve lacerations for open and closed wounds is detailed, as well as
      the presenting clinical signs and prognosis for brachial plexus avulsions,
      sciatic nerve damage, and sacrococcygeal injury.

PMID- 9020581
TI  - The growing phospholipase A2 superfamily of signal transduction enzymes.

PMID- 9020582
TI  - The aconitase family: three structural variations on a common theme.
AB  - The aconitase family contains a diverse group of iron-sulphur (Fe-S) isomerases
      and two types of iron regulatory protein (IRP). Structural comparisons have
      revealed three architecturally distinct variants in which one of the four
      structural domains is covalently linked at either the amino- or carboxy-terminal
      end of a single polypeptide or else this domain exists as an independent subunit.

PMID- 9020583
TI  - How important is the molten globule for correct protein folding?
AB  - The molten globule (MG) state is widely considered to be an important
      intermediate in protein folding and to have a polypeptide backbone with a native
      like topology. The experimental evidence for this view was obtained largely,
      however, with MG proteins containing native-like constraints. When the four
      disulphide bonds of alpha-lactalbumin were allowed to rearrange to those favoured
      by the MG, opposite conclusions were obtained. Consideration of all the
      experimental data indicates that any tendency of this MG to be native-like is
      negligible relative to all the other topologies that it can adopt. Furthermore,
      the experimental data indicate that the MG is not the key to rapid protein
      folding.

PMID- 9020584
TI  - An exception that proves the rule.

PMID- 9020585
TI  - The structure of a domain common to archaebacteria and the homocystinuria disease
      protein.

PMID- 9020586
TI  - RB kinases and RB-binding proteins: new points of view.
AB  - The retinoblastoma protein (RB) binds to a variety of cellular proteins and
      suppresses cellular growth. Such interactions are regulated by phosphorylation
      during the cell cycle by several cyclin-dependent kinases, known as RB kinases.
      Clues to the specific physiological roles of different RB kinases have been
      obtained. Moreover, interesting functions of the RB protein, other than control
      of E2F activity, have been found.

PMID- 9020587
TI  - The protein kinases of budding yeast: six score and more.
AB  - The completion of the budding yeast genome sequencing project has made it
      possible to determine not only the total number of genes, but also the exact
      number of genes of a particular type 1-3. As a consequence, we now know exactly
      how many protein kinases are encoded by the yeast genome, a number of
      considerable interest because of the importance of protein phosphorylation in the
      control of so many cellular processes.

PMID- 9020588
TI  - Protein architecture, dynamics and allostery in tryptophan synthase channeling.
AB  - The alpha 2 beta 2 form of the tryptophan synthase bienzyme complex catalyses the
      last two steps in the synthesis of L-tryptophan, consecutive processes that
      depend on the channeling of the common metabolite, indole, between the sites of
      the alpha- and beta-subunits through a 25 A-long tunnel. The channeling of indole
      and the coupling of the activities of the two sites are controlled by allosteric
      signals derived from covalent transformations at the beta-site that switch the
      enzyme between an open, low-activity state, to which ligands bind, and a closed,
      high-activity state, which prevents the escape of indole.

PMID- 9020589
TI  - Catalytic hydroxyl/amine dyads within serine proteases.
AB  - The 'catalytic triad' mechanism, which involves a serine, histidine and aspartic
      acid, has become synonymous with serine proteases. However, recently,
      mechanistically novel serine proteases have been discovered. These proteases use
      hydroxyl/epsilon-amine or hydroxyl/alpha-amine 'catalytic dyads' as their
      reactive centers.

PMID- 9020590
TI  - False positives from the yeast two-hybrid system.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methods-reagents, available on the
      Internet. This month's column discusses false positives found when using the
      yeast two-hybrid system to isolate interactive proteins. For details on how to
      partake in the newsgroup, see the accompanying box.

PMID- 9020591
TI  - The Encyclopedia of Virology plus.

PMID- 9020592
TI  - HIV/AIDS: the global epidemic, December 1996.

PMID- 9020593
TI  - Comparison of propofol and methohexitone as an induction agent in anaesthesia for
      electroconvulsive therapy.
AB  - 30 patients who received electroconvulsive therapy were anaesthetized with either
      Propofol or Methohexitone in a randomized cross-over study. Recovery times were
      shorter in those who received Propofol. The decrease in diastolic pressure after
      induction was greater with Propofol than with Methohexitone. There was a greater
      increase in the blood pressure after the electroconvulsive therapy in those who
      received Methohexitone. The duration of convulsion was similar for both agents.

PMID- 9020594
TI  - Consequences of inadvertent microbial contamination of dextrose solutions.
AB  - Most intravenous infusion fluids and non-sterile liquid products contain dextrose
      which serves as a sweetener or an energy source for critically ill or traumatized
      patients. Hence dextrose was critically examined for stability in the presence of
      some micro-organism which are commonly known to contaminated i.v. infusion
      fluids. In the presence of these test organisms, the dextrose component of these
      solutions was found to be remarkably degraded with average rates of 0.065-3.153%
      per hour depending on the type of organism. Micro-organisms such as Ps.
      aeruginosa and E. coli gave low rates of degradation of 0.065-0.88% per hour
      while the values of 0.770-3.153% per hour were obtained for K. pneumonia; B-lac+
      Staph. aureus and B. subtilis. The degradation of dextrose by C. albicans
      however, increased with dextrose concentration with average rate of 1.147-1.21%
      per hour. The degradations were gradually accompanied by increases in total
      acidity and decreases in pH of the dextrose solutions. The variation in the rates
      of degradation of dextrose by the test organisms is attributable to their
      survival rates in dextrose solutions and it is of great significance especially
      at the low inoculum size of 100 cells/ml. The results thus obtained necessitate
      the maintenance of a high level of aseptic procedures to prevent inadvertent
      contamination of i.v. fluids and other glucose containing solutions during
      clinical and other use conditions.

PMID- 9020595
TI  - Psychiatric morbidity in patients with sickle cell anaemia.
AB  - The prevalence of mild psychiatric morbidity in 38 sickle cell anaemia patients
      who had been in steady state for more than three months was compared with that of
      a matched control. Psychiatric morbidity was assessed using Goldberg general
      health questionnaire and the Leeds self assessment for depression and anxiety.
      The prevalence rate of psychiatric morbidity among the patients was 63% and among
      the control 21%. The patients had mainly mixed anxiety and depressive symptoms.

PMID- 9020596
TI  - The prevalence of sickle cell trait in Sierra Leone. A laboratory profile.
AB  - Three thousand five hundred and twenty four (1527 male and 1997 female) samples
      were screened for the presence of the abnormal haemoglobin--Sickle Cell (HbS)
      between 1990-1993. 780 (22%) of these show sickle erythrocytes in a reduced
      oxygen environment. Electrophoretic differentiation of 344 samples positive from
      the metabisulphite screening test, revealed that 76 are of the homozygous form
      with 3 being HbSC. Noting the adverse consequences on the health status of those
      affected and the expense involved in the management of such patients, there is an
      urgent need for intervention.

PMID- 9020597
TI  - Natural fluoride and trace metal levels of ground and surface waters in the
      greater Accra region of Ghana.
AB  - In a study of levels of fluoride and trace metals in ten different stations of
      both surface and groundwaters in the Greater Accra Region, Ghana, groundwaters
      were found to have lower pH than surface water, resulting in groundwaters having
      higher concentrations of dissolved ions. Groundwaters had higher fluoride levels
      than surface waters. The correlation coefficient for fluoride on total alkalinity
      and for fluoride on sodium were 0.56 and 0.27 respectively which implied that
      rock weathering played a minor role in the recorded fluoride enrichment of the
      underground waters. A likely mechanism for the higher underground fluoride levels
      could be bacterial decay of plant materials resulting in the release of fluoride
      to the underground waters. The levels of Cu, Cd, Pb and Zn fell within the
      expected background ranges. 90% of the sites had Mn levels above the detection
      limits in both underground and surface waters. 70% of boreholes in Accra plains
      had Fe levels higher than the WHO recommended limits of 0.3 mg/l for drinking
      water. Generally, underground waters had higher concentration of fluoride and
      trace metals than surface waters.

PMID- 9020598
TI  - Ocular trauma in Lagos.
AB  - 104 patients were treated for ocular trauma in Lagos from January, to December,
      1986. These were cases that needed admissions and surgery. All of them were seen
      as emergencies. Minor injuries that were treated as day cases were not included
      in this study. There is need for recording all cases at the eye clinic level for
      accurate statistics. Traditional healers, environmental and social factors vary
      the causes and final visual results. Suggestions are made to improve on these set
      backs.

PMID- 9020599
TI  - The role of ions in goitre prevalence in two local government areas of Plateau
      State, Nigeria.
AB  - This study tried to show the contributory role of ions (cations and anions) to
      great contrast in the goitre prevalence between Bassa and Jos Local Government
      Areas, both of Plateau State, Nigeria. In pursuance of this, the concentration of
      cations (Ca++, Fe++, K+, Mg++, Na+, & Zn++) and anions (C1-, F, I-, & NO-3) in
      soil and drinking water in the two LGAs were determined and their results
      compared and correlated with the goitre prevalence of these areas. It was
      observed that both Bassa and Jos LGAs have very low but similar amounts of iodide
      ions in their soils. Besides, Bassa LGA contained more ions in both soil and
      drinking water than Jos LGA. In conclusion, the results appear to suggest that
      the higher ion contents of both soil and drinking water in Bassa LGA exacerbated
      the coexisting low iodide condition of the LGA, thus resulting in the higher
      goitre prevalence found in the LGA.

PMID- 9020600
TI  - Drug susceptibility profile of Salmonella typhi blood isolates in Port Harcourt,
      Nigeria.
AB  - A study of the drug susceptibility pattern of four blood isolates of Salmonella
      typhi in Port Harcourt, Nigeria, using the disc method, revealed that all strains
      were generally sensitive to all the Gram-negative drugs tested, except for
      nitrofurantoin, neomycin and streptomycin. Three strains were moderately
      sensitive to both streptomycin (10 mcg) and neomycin (30 mcg) and resistant to
      nitrofurantoin (300 mcg) while one strain was moderately sensitive to
      streptomycin and resistant to both neomycin and nitrofurantoin. The isolates were
      highly sensitive to trimethoprim/sulfamethoxazole (25 mcg), ampicillin (10 mcg),
      ciprofloxacin (30 mcg), ceftazidime (30 mcg) and chloramphenicol (30 mcg). It is
      suggested that these strains of S. typhi could be used to develop antigens for
      more accurate results of the Widal test in Nigeria.

PMID- 9020601
TI  - Incidence of Helicobacter pylori infection in Ghanaian patients with dyspeptic
      symptoms referred for upper gastrointestinal endoscopy.
AB  - Helicobacter pylori has been linked with peptic ulcer disease, non-autoimmune
      gastritis, non peptic ulcer dyspepsia and gastric carcinoma and lymphoma. This
      study looked at the incidence of H. pylori infection in Ghanaian patients with
      dyspeptic symptoms referred for upper gastro-intestinal endoscopy and its
      relationship to various pathologies. Detection was by the CLO urease test. A
      hundred and thirty (130) patients were studied. 75.4% tested positive for H.
      pylori infection and the incidence peaks in the 5th decades. While 23.5% H.
      pylori positive patients had active duodenal or gastric ulcer, 18.8% of H. pylori
      negative patients also had the ulcer. Out of 43 patients with normal oesophago
      gastro-duodenoscopy, 74.4% were H. pylori positive, 66.6% of gastric malignancies
      tested positive for H. pylori infection. It remains to be confirmed that
      eradication of H. pylori will relieve the peptic symptoms in affected patients
      with no ulcer disease.

PMID- 9020602
TI  - Prevalence of blindness in a rural ophthalmically underserved Nigerian community.
AB  - A blindness prevalence survey was performed in Ifedapo Local Government Area of
      Oyo state in Nigeria to provide baseline data for evaluation and monitoring of
      eye care services in the area. In the ten villages selected for the survey, an
      average urban migration rate of 27.8% per year was found. 1973 persons were
      examined. Three persons were blind in both eyes and 18 were blind in one eye
      alone. Eleven people suffered low-vision in both eyes, while 35 suffered low
      vision in one eye only. The community prevalence rate of blindness (WHO
      definition) was 0.15% and prevalence rate of low-vision (WHO definition) was
      0.56%. The three blind patients were age 70, 58 and 70 years respectively. They
      were a male and two females. The mean age of the low vision-group 56 years and
      the male:female ratio was 1:2. The major causes of low-vision and blindness were
      cataracts, senile macular degeneration, glaucoma, non-trachomatous corneal
      opacities and uncorrected refractive errors. It is reckoned that 58% of the
      blindness is treatable. Another 13% could have been avoided if good ophthalmic
      services were available. About 13% was irreversible and 13% of the aetiology of
      blindness was unknown.

PMID- 9020603
TI  - Computerized tomography measures of brain slice area and ventricular sizes in
      protein energy malnutrition: a preliminary study.
AB  - The brain tissues of thirty-eight Nigerian children suffering from severe protein
      energy malnutrition (PEM) were evaluated within 24 hours of admission by
      computerized tomography. The brain slice area (B.S.A.) in marasmus (10474 +/-
      1270) is significantly smaller than those of marasmic-kwashiokor (10940 +/- 1284)
      and kwashiokor (11866 +/- 669). Similarly also the BSA of the three clinical
      types were smaller than those of the control (13134 +/- 1199), (P < 001). There
      was poor correlation of brain slice area and other parameters measured with age,
      but a significantly higher (mean) brain slice area was noticed in the males
      (11910.82) than the females (10971.67) P < 0001, in both patients and control.
      Marasmic-Kwashiokor showed marked feature of cerebral shrinkage compared with the
      other categories of PEM in all the parameters measured.

PMID- 9020604
TI  - Scope and problems of day-care surgery in a plastic surgical unit.
AB  - Interest in day-care surgery is on the increase world-wide, with various surgical
      specialties embracing this mode of health service. In a period of 5 years
      (January 1989-December 1993), 286 patients attending a Plastic Surgical Unit were
      operated on a day care basis. This represented 22.7% of all cases done within the
      period. The most frequently performed procedure was keloid excision and
      suture/flap cover (29.7%) followed by inguinal hemiorrhaphy (10.8%)
      ganglionectomy (8%), excision of lipoma (8%), scar revision (5.2%), suture of
      skin lacerations (4.5%), breast lumps biopsy (5.9), release, grafting or plasty
      of flexion deformity of fingers (3.4%). Other problems dealt with on day care
      basis included repair of human bite losses of face (3.2%); Excision of
      gynaccomastia (3.1%) umbilical hernia repair (2.4%); breast augmentation with
      implant 0.3%. Excision of planter wart, hairy naevus, chronic neck folliculitis,
      sebaceous cyst, dermoid cyst and polydactylism constituted the rest of problems
      dealt with as day cases. Readmission represents failure of day care surgery and
      constituted 2.4% of all cases. This was due mainly to social factors and bleeding
      at home. Significant wound breakdown occurred in 0.69% of cases. We conclude that
      day care plastic surgery in our subregion is safe and effective.

PMID- 9020612
TI  - Healthcare of the future.

PMID- 9020611
TI  - Medical education should not be held hostage to managed care, but tuition should
      be managed.

PMID- 9020613
TI  - Today I cut down a tree.

PMID- 9020614
TI  - Bringing managed care into focus.

PMID- 9020615
TI  - Managed care and patient care: bridging the gap.

PMID- 9020616
TI  - Working for the plan: physician autonomy under managed care.

PMID- 9020617
TI  - Doctor-led managed care organizations--the answer for you?

PMID- 9020618
TI  - Professionalism in health care delivery.

PMID- 9020619
TI  - Managed care can be better care for all citizens: a primary care perspective.
AB  - The CPN seeks to enhance the care of patients by judicious expenditure of health
      care dollars, currently for the Unit "Community" Network, but ultimately also for
      other insurers who would enter risk-sharing relationships with the CPN.
      Improvements in health care delivery will be made in enhanced access to primary
      care, including telephone access to nurse triage; in collaboration and
      communication between the selected consultant and the referring primary care
      giver, including an electronic network allowing for selected information sharing;
      and in renewing medicine's collective commitment to care provided as close to
      home as possible, or in the home if this is the highest quality. The care of the
      uninsured remains a challenge and a normal obligation from which the CPN does not
      shrink. The economic realities of primary care delivery must be improved, with
      additional resources allocated being substantially rededicated to patient care.
      The patient's control of the selection of the site of health care and the absence
      of incentives to their primary care provider for a referral pattern different
      than the patient's choice will remain important to the CPN. The CPN hopes to
      provide the diplomacy between third party payers to enhance collaboration and
      minimize competition in the delivery of care in communities.

PMID- 9020620
TI  - Improving the cost-to-benefit ratio of in-vitro fertilization.
AB  - In-vitro fertilization (IVF) has been criticized for being too costly to permit
      ready access to needy patients, either through their own funds or through those
      of third party providers. European groups have managed to offer these procedures
      at a fraction of the cost incurred by their United States counterparts by
      streamlining their protocols. Accordingly, we present our methods for reducing
      the cost of IVF. The main modification was made by performing the IVF procedures
      in the clinic under i.m. analgesia, avoiding the costs of a surgery suite and
      anaesthesia. In addition, donor, oocyte, micromanipulation, and cryopreservation
      services were not offered, reducing overall personnel and equipment costs.
      Overall costs were reduced from customary levels of $7,000--$11,000 in the United
      States to $3,409 per cycle initiated, while maintaining good ongoing/delivered
      pregnancy rates (30.0% versus 18.6% nationally) per cycle reaching aspiration. We
      conclude that, through the elimination of less necessary and/or utilized
      procedures, IVF may be performed in a more cost-effective manner while
      maintaining good success rates. For the patients who desire IVF services not
      offered under such a system, referral to a more specialized IVF center is
      appropriate.

PMID- 9020621
TI  - Professional perceptions of availability and quality of mental health services in
      Wisconsin.
AB  - Eighty-six county coordinators and psychiatrists from predominantly rural
      counties reported their perceptions of availability and quality of 21 types of
      inpatient, outpatient, and transitional living services in Wisconsin for five
      target populations: adult, children, adolescent, geriatric, and minority. Their
      ratings and priorities for addressing needs indicated (a) that transitional
      living services are insufficient and of inadequate quality for all populations;
      (b) that availability and quality of inpatient and outpatient services are better
      for adults; (c) that general needs across all populations for additional and
      higher quality services are for services that address specialized problems, both
      inpatient and outpatient; (d) that children, adolescent, minority, and geriatric
      populations have limited access to needed services; (e) that available services
      for these four groups are most often inadequate; and (f) that the needs of
      children and adolescents should be given highest priority, particularly their
      needs for transitional services and inpatient and outpatient services for special
      problems. Actions and recommendations are discussed for professionals and
      advocates to increase awareness of needs for quality services for children and
      adolescents, for expanding public information, and for design of local-county
      quality programs, including professional education and continuing outreach to
      important constituencies and advocates.

PMID- 9020622
TI  - An emerging public health perspective on domestic violence: implications for
      Wisconsin physicians and health care organizations.
AB  - In this article, we provide a brief discussion of the health and health care cost
      consequences of the problem of domestic violence, and a review of some key
      reasons why physicians may often fail to recognize the signs of this violence and
      abuse in their patients. In Wisconsin, a variety of agencies, educational
      institutions and communities are in the process of developing and refining
      educational initiatives or multidisciplinary response efforts which have medical
      care components or implications. Collectively, the experience being gained by
      these various efforts throughout Wisconsin provides a solid foundation from which
      to further develop and enhance a public health perspective for responding to
      domestic violence. It is suggested that this perspective can help inform the
      state's physicians and health care organizations on how they can improve their
      individual and organizational responses to the problem of domestic violence.

PMID- 9020623
TI  - What's new in ... rehabilitation medicine.

PMID- 9020624
TI  - Community health planning--Oneida County, 1995.

PMID- 9020625
TI  - Issues in managed care contracting.

PMID- 9020627
TI  - Managing to care--not managed care.

PMID- 9020626
TI  - Diabetic Retinopathy Project.

PMID- 9020629
TI  - The speech clinician: 'your forgotten ally'.

PMID- 9020628
TI  - Are your fees keeping pace?

PMID- 9020630
TI  - Answering the 'where' questions.

PMID- 9020631
TI  - The electronic block between you and success.

PMID- 9020632
TI  - The future of dentistry.

PMID- 9020633
TI  - Expansion and renovation.

PMID- 9020634
TI  - The empowered dental team.

PMID- 9020635
TI  - Increase your kept-appointment rate.

PMID- 9020637
TI  - Are changes in the profession compromising dental ethics?

PMID- 9020636
TI  - A practical look at the subject of fees.

PMID- 9020638
TI  - The big switch--is it right for your practice?

PMID- 9020639
TI  - The road to economic freedom.

PMID- 9020641
TI  - Building a dream office.

PMID- 9020640
TI  - The right time to discuss fees--Part II.

PMID- 9020642
TI  - Common periodontal questions answered, but everything's open for debate.

PMID- 9020643
TI  - Claim more insurance profit.

PMID- 9020644
TI  - Office reflects practice philosophy.

PMID- 9020645
TI  - Hiring exceptional staff members.

PMID- 9020646
TI  - Common traits of the million-dollar practice.

PMID- 9020648
TI  - Evolving comprehensive care.

PMID- 9020649
TI  - Marketing infection control.

PMID- 9020647
TI  - Precious-metal scrap can boost your bottom line!

PMID- 9020650
TI  - A bad idea whose time has come.

PMID- 9020651
TI  - Optimum maintenance.

PMID- 9020652
TI  - Dental malpractice claims: causes and cures.

PMID- 9020653
TI  - Ten important steps for protection of your assets.

PMID- 9020655
TI  - 'Down-home' log facility.

PMID- 9020654
TI  - Preparing for your next lease.

PMID- 9020656
TI  - Clutter hampers success.

PMID- 9020657
TI  - Barbarians at the gate?

PMID- 9020658
TI  - Ultimate patient service.

PMID- 9020659
TI  - Test yourself with the valuemeter.

PMID- 9020660
TI  - The good news and bad news about insurance.

PMID- 9020661
TI  - A big move toward growth.

PMID- 9020662
TI  - Infection control.
AB  - Sterility. Infection control. Patient protection. It's all the same thing. It's
      required and it's costly. However, we need to turn it into a positive aspect of
      our practices. The old marketing axiom still applies-you have to market your
      marketing! Stop viewing patient protection as just one more overhead expense and
      begin to use it as a benefit that can help prove how committed to your patients
      you are.

PMID- 9020663
TI  - Check it out!

PMID- 9020664
TI  - Is your practice costing you too much?

PMID- 9020665
TI  - Latest fee survey shows more dentists advertising.

PMID- 9020666
TI  - The lowest common denominator.

PMID- 9020667
TI  - Health-care credit cards can increase case acceptance.

PMID- 9020668
TI  - Subtleties of contemporary dental marketing.

PMID- 9020669
TI  - Inner-office communication.

PMID- 9020670
TI  - Are changes in dentistry compromising ethics?--Part II.

PMID- 9020671
TI  - Take charge of your future.

PMID- 9020672
TI  - The EDO--every dental office will one day be there.

PMID- 9020673
TI  - Earthquake prompts father, son practice.

PMID- 9020674
TI  - Direct reimbursement--a practical approach that works.

PMID- 9020675
TI  - High-tech has arrived in dentistry.

PMID- 9020676
TI  - Give your office more credit.

PMID- 9020677
TI  - Shhhh!! Don't say that word!

PMID- 9020678
TI  - Technology overload?

PMID- 9020680
TI  - The 12 commandments of dental computing.

PMID- 9020679
TI  - Electronic vs. traditional recordkeeping.

PMID- 9020681
TI  - Opening your practice's profit window.

PMID- 9020682
TI  - Staff retention and the power of praise.

PMID- 9020683
TI  - Make hygiene profitable.

PMID- 9020685
TI  - Making every inch count.

PMID- 9020684
TI  - Passive investing for the active dentist.

PMID- 9020686
TI  - Biomedical research, data accumulation, and scientific etiquette.

PMID- 9020687
TI  - Log-linear allometry of fetal craniofacial growth in Down's syndrome.
AB  - Trisomy 21 develops as a result of nondisjunction of two homologous chromosomes
      during either the first or second meiotic division. One of the more important
      consequences of these genetic alterations is the predictable, although variable
      disturbance in the architecture of the craniofacial region [1]. Postnatal
      craniofacial morphology has been extensively studied in Down's syndrome (DS).
      However, little information is available on human prenatal development of the
      head and face in such patients. The time at which changes in craniofacial
      phenotype first emerge in Down's syndrome fetuses and at which physical growth
      begins to diverge from normal is unknown. To explore these questions, we compared
      prenatal craniofacial growth in 50 Down's syndrome fetuses with that of 555
      fetuses judged to be "typical for body weight and age" using the method of log
      linear allometry [2].

PMID- 9020688
TI  - Log-linear allometry of normal fetal craniofacial growth.
AB  - Normative data on human craniofacial growth during the fetal period and important
      to provide a broader perspective on normal morphogenesis as well as to serve as
      reference for analyzing craniofacial syndromes in which growth has gone awry.
      Over a 19-year period, the Teratology Unit at the University of Michigan Medical
      Center has collected data on 2,568 legally donated fetuses that have undergone
      necropsy examination at various gestational ages. From previous analyses, 609 of
      the total fetal population (25%) were designated as typical for age or body
      weight on the basis of normal morphology, absence of maceration, and general
      growth symmetry. Of the 609 fetuses reviewed, 54 were excluded secondary to
      incomplete data. The remaining 555 constitute the basis of this study. Seven
      craniofacial measurements were recorded, including head circumference (HC), brain
      weight, inner canthal and outer canthal distances, and distances from nasion to
      menton, outer canthus to tragus and auditory meatus to vertex. Statistical
      analysis was carried out using the single-factor allometric model of Sewall
      Wright. Size was estimated as the first unstandardized principal component of the
      logarithms of lengths and of cube roots of weights, and then allometry was
      expressed in the regressions of each log variable on size. Significant allometry
      was found as were significant differences in errors about the allometric
      relation, but no evidence for more than a single factor or of "nonlinearity" in
      the regression curves was noted. Although there were differences of specific
      allometric coefficients between the various measurements (i.e., the slope of the
      curve for IC was significantly smaller than the slope of the curve generated for
      HC), these specific growth rates remain in relatively strict proportion to one
      another from early in gestation (body weight, 54.2 gm) to later in gestation
      (body weight, 1,000 gm).

PMID- 9020689
TI  - Ethylene oxide gas sterilization does not reduce the osteoinductive potential of
      demineralized bone in rats.
AB  - It has been shown that different sterilization procedures of demineralized bone
      may influence its osteoinductive properties. The aim of this study was to
      evaluate the effect of ethylene oxide sterilization for 1, 3, and 6 hours on the
      osteoinductive potential of allogeneic demineralized bone implanted
      heterotopically in rats. Sixty male Wistar rats were randomly assigned to one of
      four groups, A through D, and four demineralized bone chips (2.8 mg) were
      implanted in a pouch created between the right oblique abdominal muscles in each
      animal. In Group A, the demineralized bone was implanted without prior
      sterilization of the material, whereas the demineralized bone implanted in Groups
      B, C, and D had been sterilized in ethylene oxide gas for 1, 3, or 6 hours,
      respectively, and aerated for 48 hours. At 4 weeks postoperatively, bone
      formation was evaluated quantitatively by strontium 85 uptake and qualitatively
      by light microscopy of histological sections. One-way analyses of variance at the
      0.05 level revealed no significant difference in strontium 85 uptake of the
      different groups, and no qualitative differences in osteoinduction could be
      detected by light microscopy. Ossicles consisting of bone and bone marrow were
      seen in the recovered implants of all groups.

PMID- 9020690
TI  - "Piggyback" osteotomies in craniomaxillofacial surgery.
AB  - The total correction of severe skeletal dysplasias in patients with craniofacial
      anomalies can often be limited by the use of standard osteotomy designs. In this
      report, we emphasize the concept of the "piggyback" osteotomy for the correction
      of severe skeletal dysplasias. The piggyback approach, which uses the tiering or
      stacking of one osteotomy segment on another, allows the reconstructive surgical
      team to address multiple skeletal problems in one operative setting adequately.
      The use of this approach throughout the entire craniomaxillofacial skeleton is
      illustrated with several clinical examples. The conceptual importance of the
      piggyback principal and the rationale behind its application are discussed.

PMID- 9020691
TI  - Treacher Collins syndrome: early surgical treatment of orbitomalar malformations.
AB  - In the past various materials have been used for the correction of the malar bone
      defect, such as cartilage, dermis fat, silicone, autograft, homograft, xenograft,
      and free bone transplantation. The disadvantages of inorganic implants are well
      known: dislocation, extrusion, and capsular contraction. The bony autograft has
      no growth potential, and children may need several complementary corrections.
      None of these procedures is totally satisfactory. To solve these problems malar
      reconstruction is performed with the help of a temporal bone flap. Two varieties
      of these flaps have been described: one anteriorly with a muscular pedicle
      vascularized by the deep temporal artery and one posteriorly with a galeal
      pedicle vascularized by the superficial temporal artery. The main advantage of an
      osteomuscular flap is the survival of bone once it has been transferred. The
      second advantage is related to the osteogenic potential of the cambium layer of
      the periosteum, which may prove to be an ongoing concern. Our series of patients
      includes 20 children. Correction of the eyelid coloboma was obtained by
      transposition and advancement of a superior palpebral flap.

PMID- 9020693
TI  - Commentary on correction of sagittal craniosynostosis.

PMID- 9020692
TI  - Effect of insulin-like growth factor type 1 on critical-size defects in diabetic
      rats.
AB  - A number of investigators have reported on the clinically significant
      relationship between diabetes mellitus and impaired wound healing. Diabetic
      patients have an increased frequency of infection, delayed scar formation, and
      poor bony union. Investigations completed in our laboratory have demonstrated
      that insulin-like growth factor type 1 (IGF-1), a somatomedin C, has shown
      promise for accelerating bony repair. The purpose of this study was to examine
      the effects of recombinant IGF-1 on standardized, critical-size calvarial defects
      in 25 adult, male streptozocin-induced diabetic rats. From our study, it appears
      that IGF-1 exerts a potentiating effect on the repair of bony defects in diabetes
      induced rats.

PMID- 9020694
TI  - Costochondral reconstruction of mandibular condyles in nongrowing primates.
AB  - The aim of this study was to develop a reproducible model in nongrowing animals
      to document morphological and histological changes after costochondral
      reconstruction of the mandibular condyle. Seven adult monkeys underwent a
      unilateral condylectomy followed by costochondral reconstruction. Dimensional
      changes of the thorax and reconstructed ramus-condyle unit were documented by in
      situ and radiographic analysis. Morphological and histological analysis were
      completed after removal at 4 (n = 2), 8 (n = 2), and 12 months (n = 3). In situ
      measurements demonstrated no dimensional changes of the thorax, but the
      reconstructed ramus-condyle unit decreased in height an average of 3.2 +/- 1.4
      mm. The original graft remained unchanged morphologically, but new bone and
      cartilage progressively encompassed it, creating a form similar to the native
      condyle. Histologically, the transplanted cartilage remained unchanged. However,
      the articulating surface progressively took the appearance of the native condyle.
      Results of this study indicated that, in nongrowing animals, the reconstructed
      ramus-condyle unit decreases in height slightly but remodels to a size and shape
      morphologically and histologically similar to the native condyle.

PMID- 9020695
TI  - Efficacy of hydroxyapatite ceramic as a carrier for recombinant human bone
      morphogenetic protein.
AB  - In this study, we investigated the efficacy of hydroxyapatite ceramic (HAP) as a
      carrier of bone morphogenetic protein (BMP) using porous HAP pellets artificially
      fabricated from limestone. After treatment with recombinant human BMP-2, the
      pellets were inserted beneath the cranial periosteum of rabbits, and the degree
      of osteogenesis was examined histologically. The degree of osteogenesis was also
      evaluated using image-analyzing procedures. Results showed that extensive bone
      formation had occurred around the pellets 3 weeks after insertion in the group
      that received pellets treated with recombinant human BMP alone as well as in the
      group that received recombinant human BMP in addition to type I collagen-treated
      HAP pellets. Subsequently, osteogenesis within the pellets slowly progressed over
      time, and by 9 weeks after insertion most of the pellet pores in both groups were
      filled with newly generated bone. The recombinant human BMP-collagen group,
      however, exhibited a significantly greater bone induction. These results
      indicated that if recombinant human BMP is used clinically in the future,
      artificially fabricated HAP would be a suitable carrier.

PMID- 9020696
TI  - Crouzon's disease correlates with low fibroblastic growth factor receptor
      activity in stenosed cranial sutures.
AB  - Reports have demonstrated that Crouzon's disease is associated with a gene on
      chromosome 10 coding for the fibroblastic growth factor (FGF) receptor 2. The
      purpose of this investigation was to evaluate the FGF receptor 2 levels in
      cranial sutures of children with Crouzon's disease and nonsyndromic, isolated
      craniosynostosis. Twelve children between the ages of 6 and 24 months were
      studied. Four patients had Crouzon's disease with coronal suture stenosis. The 8
      remaining had a nonsyndromic, isolated coronal stenosis. Stenosed and adjacent
      nonstenosed cranial sutures were removed at cranioplasty and promptly fixed,
      decalcified, and embedded in paraffin. Immunohistochemical analysis of cranial
      sutures was performed with labeled, specific anti-FGF receptor 2 antibodies. In
      children with Crouzon's disease, we found significantly lower levels of FGF
      receptor 2 staining in stenosed sutures compared with nonstenosed sutures. In
      addition, sutures from children with Crouzon's disease demonstrated lower levels
      of FGF receptor 2 activity in both stenosed and nonstenosed sutures compared with
      children with a nonsyndromic, isolated coronal stenosis. However, there were no
      significant differences in FGF receptor 2 staining between stenosed and
      nonstenosed sutures in children with a nonsyndromic, isolated coronal stenosis.
      These findings suggest that low FGF receptor 2 activity in cranial sutures
      correlates with Crouzon's disease. This work supports genetic studies and yet
      shows that patients with Crouzon's disease have low FGF receptor 2 activity in
      cranial sutures. The findings also suggest that there may be etiological
      differences between syndrome- and nonsyndrome-associated craniosynostoses in
      children.

PMID- 9020697
TI  - Occipitoparietal bone flap for mandibular reconstruction.
AB  - Mandibular reconstruction may prove to be a difficult problem. The use of
      vascularized bone flaps for mandibular reconstruction has shown better results
      than bone grafts because they offer solid bone union together with rapid recovery
      of form and function. The occipital vessels, from the external carotid artery and
      the jugular vein up to their site of emergence in the occipital fascia, have
      proved easy to dissect at the neck after section of sternocleidomastoid and
      splenius capitis longus and brevis muscles. We were able to obtain a long pedicle
      to move the fascia to distant sites with or without bone. Reconstruction was
      achieved with a full-thickness occipitoparietal bone flap, pedicled at the
      occipital vessels, released up to the external carotid artery to yield a long
      pedicle. We used this technique in four patients (age range, 8-14 years). We used
      vascular cranial bone for mandibular reconstruction. The cases included three
      resections for benign tumors (two fibromyxoma and relapsing aneurysmal bone cyst)
      and one hemifacial microsomia. No complications occurred. We describe some
      advantages with this procedure. A larger number of cases will allow us to draw
      further conclusions.

PMID- 9020699
TI  - Does "biological predeterminism" apply to patients born with craniofacial
      disorders?

PMID- 9020698
TI  - A simple method to harvest dural grafts.
AB  - A small rectangular wire loop was designed to harvest dural graft from rats. This
      loop was used successfully to take 40 dural grafts from 20 infant and 20 adult
      rats. The technique is presented in detail.

PMID- 9020700
TI  - Maxillofacial surgery within plastic surgery: "the Kazanjian Lecture, 1993".

PMID- 9020701
TI  - Interaction of craniofacial dysmorphology, growth, and prediction of surgical
      outcome.
AB  - Craniofacial surgery is a multidisciplinary specialty that often uses the
      expertise of many specialists including surgeons, orthodontists, geneticists, and
      anthropologists. The clinical experience gained by their collaboration enables
      predictions to be made of the ultimate success of the reconstructive surgery.
      Various patterns among surgical outcomes are noted as greater experience is
      gained. These observations prompted the following questions: Is there a way to
      classify patients according to surgical results? What factors underlie a
      successful response to surgery? In a clinical setting, we are faced with a
      spectrum of presentations of craniofacial dysmorphology. We propose that the
      results of surgical correction may be based on the cause of the condition and not
      necessarily on the degree or character of the dysmorphology. Craniofacial
      dysmorphologies are often grouped under the terms deformation, malformation,
      disruption, dysplasia, or syndrome. Our hypothesis is that a categorization of
      craniofacial dysmorphology can be proposed on the basis of the response of the
      individual to surgery. We propose that such a classification reflects real
      differences in cause. A poor response to surgery reflects a condition that
      includes a growth disorder. Alternatively, cases that respond best to surgery are
      those in which the growth process is not affected. In the latter cases, a
      dysmorphic face is surgically transformed into an acceptable morphology, and
      normative growth vectors maintain or improve postoperative facial appearance. It
      is our belief that the physiological differences underlying our categorization
      scheme have to do with embryological timing of insults or specific components of
      the ontogenic process. The divergence in the response to surgery among patients
      relates directly to the role of the growth process in the various types of
      dysmorphologies.

PMID- 9020702
TI  - Biodegradable polyglyconate plates and screws: a histological evaluation in a
      rabbit model.
AB  - Within the zygomatic arch, bilateral osteotomies were performed on 20 adult male
      New Zealand white rabbits. These were stabilized in an anatomical position with
      polyglyconate acid plates and screws. At 3, 4, 6, 9, and 12 months, rabbits were
      killed and their zygomatic complexes removed en bloc. Specimens were serially
      sectioned for standard histological examination. Although no gross reactions were
      noted throughout the course of this investigation, histological reactions were
      brisk. At 3 months, particulate material was surrounded by a foreign body giant
      cell-type reaction. The quantity of foreign material appeared to decrease by 4
      months, at which time the foreign body reaction was partially replaced by fibrous
      tissue. By 6 months, there was a thick periosteal scar at the osteotomy site with
      a few islands of persistent foreign material. These were primarily seen in small,
      irregular vesicular spaces surrounded by a large number of histiocytes with their
      characteristic foamy-cytoplasm. Although this foreign body reaction had subsided
      by 12 months, small foci of chronic inflammation still persisted.

PMID- 9020703
TI  - Biomechanical evaluation of the canine and porcine models for experimental
      craniofacial surgery.
AB  - This investigation compared the variation of the biomechanical properties of
      canine and porcine craniofacial bones in homotypical (same site in opposite sides
      of an animal) and heterotypical (same site in different animals) sites.
      Biomechanical analysis is a reliable method to assess bone healing, because
      fracture repair correlates closely with the changes in biomechanical properties.
      Paired bone fragments were harvested in nine dogs and nine minipigs from each
      side of the skull from three different sites-the frontal bone, the supraorbital
      rim, and the zygomatic arch- and submitted to torque to failure. Maximum torque,
      stiffness, and toughness were recorded and comparative analysis performed. A
      normal range of variation between paired craniofacial bones in two useful animal
      models is provided. The results showed that the variability between homotypic
      left and right sides was not significant, whereas the variability between
      heterotypic sites in separate animals was. Maximum torque was the most reliable
      of the three parameters considered, because the data fell over a much narrower
      range. We conclude that the use of the contralateral side is a valid control in
      experimental procedures that may alter the biomechanical properties of one side.

PMID- 9020704
TI  - Passive and active intracranial translocation of osteosynthesis plates in
      adolescent minipigs.
AB  - On the basis of the clinical and experimental proof that intracranial
      translocation of osteosynthesis plates occurs in infants after fixation on
      frontal bone, we conducted an animal study on four adolescent Gottingen minipigs.
      Our aim was to study the effects on intracranial translocation of two different
      types of osteosynthesis plates by comparing the plate-bone interface on the
      intact frontal bone treated with a multiple-point contact plate versus a
      conventional smooth one, paying special emphasis to the periosteum. Within a few
      weeks of implantation, osseous regeneration products surrounded the plate. Total
      invagination of plates with initial intracranial translocation occurred 12 to 16
      weeks postimplantation, regardless of plate design. In epiperiosteal fixation,
      intracranial translocation was delayed. The results revealed two mechanisms at
      play here: cranial growth-related passive intracranial translocation, which
      occurs regardless of plate design, and plate-dependent active intracranial
      translocation. In conclusion, we recommend that all metal osteosynthesis
      materials implanted in the infant cranium be removed as early as possible (within
      3 months).

PMID- 9020705
TI  - Critical review of microfixation in pediatric craniofacial surgery.
AB  - The migration or passive intracranial translocation of microplates and screws in
      the pediatric craniofacial patient has been reported. A retrospective review was
      undertaken to clarify the incidence of microplate translocation and identify
      potential clinical implications. Computed tomographic imaging demonstrated
      internalization of microfixation in 14 of 27 pediatric patients. Statistically
      significant factors for microplate translocation include longer plates (p < 0.05)
      and those placed in the temporal region (p < 0.001). Younger patients and those
      with syndromic craniofacial dysostosis also had a higher incidence of
      translocation. Specific complications relating to the translocation of
      microplates were not found in any patient. The direct effects of translocated
      microplates and screws on the underlying brain and dura remain unclear.

PMID- 9020706
TI  - "False" migration of rigid fixation appliances in pediatric craniofacial surgery.
AB  - Osseous fixation techniques have been widely used to provide rigid stabilization
      in the craniofacial skeleton. Reported sequelae of its usage has been limited to
      palpation of the screw-plate system and radiological imaging artifacts. Over the
      past 3 years we have identified miniplates, microplates, and wire sutures on the
      inner cranial table of the growing child. The observation of "false" migration of
      these appliances has provided the impetus to review these patients in more
      detail. Twenty patients underwent secondary cranial remodeling within a two-year
      period; 7 of these patients were seen to have "false" migration. There were no
      untoward sequelae in removal of these appliances, and no adverse neurological
      symptoms were seen.

PMID- 9020707
TI  - Influence of craniofacial surgery on the social attitudes toward the malformed
      and their handling in different cultures and at different times: a contribution
      to social world history.
AB  - A historic overview including the European, American, Asian, and African
      continents is given on attitudes toward and the handling of humans with
      congenital malformations in ancient cultures and on pertinent customs in some
      prehistoric peoples. Figures of early works of art showing malformed individuals
      are presented testifying to this worldwide and timeless problem of humankind. In
      parallel, analogous patient photographs from our hospital before and after
      reconstructive surgery are shown. Philosophies of ancient Greece, rome, and China
      on the subject of malformed infants essentially did not differ from the known
      attitudes of the less developed tribes in Europe and pre-Columbian America,
      although the means of elimination of unwanted offspring were rather passive
      (exposure) than active (manual killing). A radical change in attitudes and
      practices occurred with the spread of the Christian religion and its political
      installment in Europe. The care for the underprivileged including the malformed
      ones was considered a Christian duty to be performed with compassion and love. In
      our century, the clocks have been and apparently are turned back again. Atheistic
      and Darwinian influences, political atheism, and the belief in "higher ethics"
      issued by "superman" have led to a relapse into barbarism, also within the
      medical system. We, as craniofacial surgeons, are privileged to have the means to
      turn the clocks forward again by rehabilitating the physically most
      underprivileged: those with conspicuous craniofacial malformations. The necessary
      techniques exist and are applied, as the figures of patients from our hospital
      demonstrate, but the will and the emotional strength for their consequent
      application require more than our hands.

PMID- 9020708
TI  - Delayed development of an ectopic frontal sinus mucocele after pediatric cranial
      trauma.
AB  - We describe the delayed occurrence of a frontal sinus mucocele 14 years after the
      original trauma. The patient presented with a laterally displaced, enlarging mass
      that encroached on the dura. The sterile mucocele was removed, and the cranial
      defect was reconstructed with methyl methacrylate and wire mesh. Our experience
      confirms the known but rarely observed late development of a mucocele after
      pediatric facial trauma. To prevent the sequela of mucocele development, the
      mucosa of the rudimentary frontal sinus in the pediatric patient must be
      carefully sought and ablated during reconstructive procedures of the forehead
      when traumatic injury significantly disrupts the normal bony anatomy.

PMID- 9020709
TI  - Massive craniofacial osteolysis.
AB  - Involvement of the craniofacial skeleton by the process of massive osteolysis has
      been infrequently recorded. We describe a patient whose extent of
      craniomaxillofacial bony loss defied combined reconstruction by combined
      autogenous tissue and alloplastic materials. The clinical and radiographic
      features and management approaches to massive osteolysis are reviewed.

PMID- 9020711
TI  - The structure and function of regenerated bone.

PMID- 9020710
TI  - Intraoperative scalp management in craniofacial surgery.
AB  - A simple hair-braiding technique is presented as an adjunct for the
      intraoperative management of the scalp in patients undergoing craniofacial
      reconstruction with exposure through a coronal incision. The method is described,
      and its practical advantages over standard approaches are discussed.

PMID- 9020712
TI  - Some possibilities with our method for treating damage to and disorders of
      locomotor apparatus.

PMID- 9020713
TI  - What constitutes adequate bone formation in the craniofacial skeleton?

PMID- 9020714
TI  - Effect of mandibular distraction on the temporomandibular joint: Part 1, Canine
      study.
AB  - The effect of osteodistraction on the temporomandibular joint was evaluated in a
      canine model. Eleven mongrel dogs were used in the study. An intraoral expansion
      device was placed after an osteotomy was made at the angle of the mandible via an
      intraoral approach. The mandibles were expanded either fully to 20 mm or
      partially to 10 mm. After expansion, nine animals were immediately killed; the
      remaining two were maintained in fixation for an additional 10 weeks.
      Cephalometric radiographs and computed tomographic scans obtained preoperatively
      and before killing were evaluated. No gross temporomandibular joint deformation
      or bodily movement was noted in the expanded or contralateral, unexpanded side.
      The temporomandibular joints were harvested en bloc for gross and microscopic
      evaluation. Flattening of the posterior aspect of the expanded condylar head was
      noted, with thinning of the condylar cartilage. New bone deposition was noted,
      which was evident as anterior lipping. Condyles maintained in 10 weeks fixation
      showed reparative changes. No evidence of avascular necrosis, microfracture, or
      cystic degeneration was noted. This study indicates that the force of distraction
      can induce bony changes in the temporomandibular joint and that these effects are
      minimal and reversible.

PMID- 9020715
TI  - Effect of mandibular distraction on the temporomandibular joint: Part 2, Clinical
      study.
AB  - Mandibular lengthening by gradual distraction has been gaining popularity.
      However, the effect of osteodistraction on the temporomandibular joint has been
      evaluated in patients with craniofacial anomalies who underwent mandibular
      distraction. Five patients had unilateral expansion and five had bilateral
      expansion. The mandibles were expanded 1 mm per day until the pogonion was in the
      midline. Preoperative, immediate, 6-month, and 12-month panoramic and
      cephalometric radiographs were evaluated. In unilaterally expanded mandibles, the
      ipsilateral condyle increased in size and volume, became more upright, and was
      oriented in a more normal vertical axis. The contralateral unexpanded condyle did
      not show deformational changes. In those mandibles that were bilaterally
      expanded, both condyles increased in size and volume and became more symmetrical
      and upright. Osteodistraction appears to affect bone in both local and distant
      sites. The expanded condyles were stimulated to ensure a more nearly normal
      shape, size, and configuration.

PMID- 9020716
TI  - Distraction osteogenesis of the human craniofacial skeleton: initial experience
      with new distraction system.
AB  - Application of distraction osteogenesis to the human craniofacial skeleton in
      properly selected cases represents a major advance in the treatment of
      craniofacial deformities. We report our initial clinical experience with a system
      of miniature distraction devices that permitted maxillary, orbital, and
      mandibular distraction in a 4-month-old boy with unilateral craniofacial
      microsomia and anophthalmia. At 6 months of age, after maxillary repositioning
      and orbital expansion, a costochondral rib graft was used to construct the
      missing left mandibular ramus and condyle.

PMID- 9020717
TI  - Staged repair of secondary cleft palate deformities.
AB  - Despite improvements in cleft palate surgery, residual oronasal fistulas remain a
      frustrating problem for plastic and reconstructive surgeons because of a high
      incidence of failure when scarred and immobile neighboring palatal mucoperiosteum
      is used for secondary closure. Therefore, my colleagues and I have found it
      necessary to introduce additional tissue from regional sites to close persistent
      oronasal fistulas. Although each technique may have its successes, no one method
      can be consistently depended on to repair large palatal fistulas. Even with
      regional flaps, dehiscence from a scarred surgical site is quite frequent.
      However, these flaps may still provide satisfactory coverage with staged
      reconstruction because they will frequently close a significant percentage of the
      overall defects, which then may be reused to close the remaining defect.

PMID- 9020718
TI  - Johanson-Blizzard syndrome facial anomaly and its correction using a
      microsurgical bone graft and tripartite osteotomy.
AB  - The facial anomaly of Johanson-Blizzard syndrome and its correction are
      described. The facial anomaly was characterized by cleft-like bony defects
      located in the inferomedial portion of the orbit apart from the hypoplastic
      maxilla and the absence of nasal alae. Correction of the facial skeleton was
      performed using a free vascularized iliac bone graft and tripartite osteotomy to
      correct the shape of the orbit and elongate the severely hypoplastic maxilla.
      Those procedures were effective to a certain degree in correcting the facial
      anomaly of Johanson-Blizzard syndrome.

PMID- 9020719
TI  - Frontonasal encephalocele and associated congenital brain tumor.
AB  - A rare case of frontonasal encephalocele associated with a congenital brain tumor
      is presented. We describe our combined extracranial and intracranial approach to
      correction of frontonasal encephaloceles. A discussion of frontonasal
      encephaloceles and neonatal brain tumors follows, with a discussion of
      embryopathogenesis and surgical correction.

PMID- 9020720
TI  - Median lip fissure.
AB  - Forty-two cases of median lip fissures are reported. The majority of these had
      earlier been treated conservatively without healing. All cases were corrected by
      surgery, the first 10 by excision only, the remaining 32 by excision combined
      with Z-plasty. In the first group, one total and one partial relapse occurred; in
      the second group all patients healed uneventfully. Pedigrees were obtained and
      indicated that a hereditary component in the cause exists. The location of and
      the resistance to conservative treatment may suggest that these lesions that seem
      to be due to a weakness in the lip may be very discreet manifestations of the
      cleft, which, in more severe cases, was classified as no. 30 by Tessier.

PMID- 9020721
TI  - Blepharolabioanal syndrome.
AB  - A previously unreported syndrome of congenital craniofacial and anorectal
      anomalies affecting a woman and her two daughters is described. Features include
      bilateral cleft lip, cleft palate, bilateral upper and lower lid lag, and
      imperforate anus. The findings are consistent with an autosomal dominant pattern
      of inheritance. There were no identifiable intrauterine fetal insults. A detailed
      description of these anomalies, the subsequent surgical corrections, and a
      discussion of previously unreported syndromes with isolated features are the
      subject of this report.

PMID- 9020722
TI  - Geometric evaluation of mandibular distraction.
AB  - In planning mandibular distraction, the deficiency of the vertical ramus and body
      is measured. The position of the pin placement is evaluated by the following
      formula: [formula: see text] This is more accurately presented by the new
      formula. [formula: see text] In one patient the original formula evaluated the
      pin placement angle to be 9.94, compared with 9.92, in the more accurate but more
      complex new formula. When the gonial angle is obtuse, the difference is small.
      When the gonial angle is more acute, as in a normal gonial angle for a 2-year-old
      child--134 degrees--the difference is still only 0.1 degree. The original formula
      is simpler to use and is accurate enough for clinical use in mandibular
      distraction. The distraction distance is not the sum of the vertical ramal
      deficiency plus the body deficiency but is given by the following formula:
      [formula: see text] It would be accurate enough to plan the total distraction
      distance to be less than the sum of the two distances. The more acute the gonial
      angle is, the less the distraction distance will need to be.

PMID- 9020723
TI  - Central nervous system imaging in Crouzon's syndrome.
AB  - Although the need to prevent the secondary effects of craniosynostosis on the
      central nervous system is fundamental to the practice of craniofacial surgery,
      the detailed structural anatomy of the central nervous system in the syndromal
      craniosynostoses has become the subject of recent interest. A clinical and
      radiographic review of a population of 59 patients with Crouzon's syndrome
      determined the frequency of central nervous system deformities. Twelve percent of
      patients had evidence of decreased mental function. Ventriculomegaly on computed
      tomographic scan was present in 51% and found to be of three grades: mild,
      moderate, and severe (hydrocephalus). This was nonprogressive in 7 of the 11
      patients with follow-up computed tomographic scans. Ten patients underwent
      surgical release to increase intracranial space; however, 6 of these patients
      showed no progression in ventricular size. Nonventricular anomalies were found
      less frequently (14%). Central nervous system findings show fewer nonventricular
      anomalies than in Apert's syndrome patients, with a corresponding higher mental
      function. The principal anomaly of ventriculomegaly is not directly related to
      suture defect and may represent a primary brain abnormality. Recommendations are
      made for the assessment and management of patients with Crouzon's syndrome with
      reference to these areas.

PMID- 9020724
TI  - New option for anterior traction of the face by using a cervical collar.
AB  - This case required anteroposterior traction of the maxilla. Once none of the
      traditional methods could be used because of the lack of support in the chin and
      in the frontal region. Thus, we opted to use a cervical collar.

PMID- 9020725
TI  - Midforehead incision: an approach to the frontal sinus and upper face.
AB  - The coronal incision has established itself as the principal surgical approach to
      the forehead. It allows for a well-hidden scar and a wide field of surgical
      exposure. The midforehead incision, described in the brow-lift literature, is a
      cosmetically acceptable alternative to the coronal incision for patients with
      forehead wrinkles or who are at risk for male pattern baldness. In an analysis of
      33 consecutive open frontal sinus procedures, we compared patients who underwent
      i coronal approach to a midforehead approach for operative time, blood loss,
      length of hospital stay, and cosmetic result. There was a trend toward decreased
      operative time and decreased blood loss with the midforehead approach. The
      cosmetic result was acceptable in all patients. We advocate the use of a
      midforehead approach to the frontal sinus in patients with deep forehead creases
      and with hairline recession and elderly or infirmed patients who cannot tolerate
      prolonged procedures or significant blood loss.

PMID- 9020726
TI  - Reactivation of a mandibular lengthening device for maximal distraction.
AB  - A technique for reactivating the Howmedica mini-lengthening device is presented.
      This procedure, performed in the clinic, allows for mandibular distraction in
      excess of the standard maximum of 25 mm.

PMID- 9020727
TI  - A future domain distractor for the facial skeleton.
AB  - A new device was designed based on the Ilizarov principle. The design is a new
      configuration of the external components. The 0.9-mm pins are similar to those
      used in bone fixation during the last 15 years, are bicortical, and utilize hand
      torque for insertion.

PMID- 9020728
TI  - Use of temporary miniplate for fixation in cases of mandibular fracture.
AB  - Luhr miniplate is used for temporary fixation and adjustment so that ideal
      occlusion and fracture alignment can be achieved. In this procedure, the lower
      edge of the mandible is first temporarily fixed, and precise bone alignment is
      achieved through dynamic compression using the temporary miniplate. Afterward,
      one or more miniplates are attached on the ideal line to maintain structural
      integrity during bone restoration. This method is a simple restoration technique
      that allows temporary auxiliary fixation to assist precise attachment of the
      manipulative miniplate. No special instrument or devices are required. It is,
      therefore, quite beneficial as an auxiliary technique for reconstructive surgery
      of this type.

PMID- 9020730
TI  - The peer review process.

PMID- 9020729
TI  - Monobloc craniomaxillofacial distraction osteogenesis in a newborn with severe
      craniofacial synostosis: a preliminary report.
AB  - Severe craniofacial synostosis can be a devastating problem for a newborn infant.
      Reasons for early surgical intervention include cranial stenosis, hydrocephalus,
      inadequate globe and corneal protection, compromised airway patency, and feeding
      problems. In this preliminary report, we describe the management of severe
      craniofacial synostosis in a newborn infant by means of cranial and midfacial
      distraction osteogenesis.

PMID- 9020731
TI  - Recent advances in craniofacial genetics.

PMID- 9020732
TI  - A three-dimensional smooth surface analysis of untreated Crouzon's syndrome in
      the adult.
AB  - This study compares the three-dimensional smooth surface shape of five adult
      patients with Crouzon's disease with nine normal skulls. A new analysis method is
      described which is based on smooth surface curvature. Surface samples are
      subdivided by a common ridge curve structure. Three-dimensional images of an
      average normal and an average Crouzon skull are illustrated. Comparisons between
      groups are performed on landmarks, as well as ridge curve and surface patch
      midpoints. There was as much discriminant information in the ridge curves and
      surface patches between landmarks as there was at the landmarks themselves. When
      compared with normal samples, the Crouzon's syndrome sample exhibits the
      following major characteristics: The midface is concave and wide, with the
      piriform aperture in the center more recessed than the perifery of the midface.
      The forehead is recessed above a frontal sinus bulge. The orbits are shallow,
      wide, concave, and tilted inferiorly with a mild hypertelorism. These data
      suggest that advancement of large, one-piece osteotomy segments will not produce
      a normal face, and a multisegment approach should be considered.

PMID- 9020733
TI  - A new instrument design for orbital floor osteotomies performed by an intraoral
      approach.
AB  - A new osteotome is described that enables the creation of an osteotomy of the
      orbital floor by an intraoral approach. The osteotome is S shaped and 11 cm long,
      with a curved cutting edge that is inserted like a hook onto the orbital floor.
      The main body and striking head of the osteotome are located just outside of the
      oral cavity. The S shape of the handle allows for ease of both insertion and
      instrument use. The new osteotome makes it possible to follow a specifically
      designed osteotomy line along the orbital floor, ensuring a rapid and reliable
      procedure.

PMID- 9020735
TI  - Temporal fascial periosteal and musculoperiosteal flaps in the pig: design and
      blood flow assessment.
AB  - The availability of a vascularized periosteal flap with bone-forming potential
      could greatly enhance the reconstructive capabilities of the craniofacial
      surgeon. Previous observations seem to indicate that the bone-forming potential
      of periosteal flaps depends on the vascularity of the flap. The purpose of the
      present experiment was to design temporal fascial periosteal and
      musculoperiosteal flaps in the pig and to compare the periosteal blood flow with
      unoperated periosteum in the same location. The radioactive microsphere (15
      micron diameter) technique was used to measure periosteal capillary blood flow in
      periosteal flaps and unoperated control, randomized to each side of the head in
      nine pigs (Yorkshire; weight, 12-14 kg). The periosteum was (1) raised based on
      the temporalis muscle with vascular supply from the deep temporal vessels (n =
      6), (2) raised based on temporoparietal fascia-deep temporal fascia with blood
      supply from the superficial temporal vessels (n = 6), or (3) left intact (n = 6).
      The mean periosteal capillary blood flow rates in the intact periosteum (0.107 +/
      0.001 ml/min/g), the temporal musculoperiosteal flaps (0.081 +/- 0.01 ml/min/g),
      and temporal fascial periosteal flaps (0.087 +/- 0.012 ml/min/g) were not
      significantly different. These observations indicate that the blood flows for
      both musculoperiosteal and fascial periosteal flaps were comparable to control
      intact temporal periosteum.

PMID- 9020734
TI  - Polyglyconate fixation successfully stabilizes zygomatic osteotomies in a
      nonhuman primate.
AB  - Investigators have reported problems with metal plates and screws, including
      restriction of craniofacial growth necessitating secondary removal; bone
      resorption secondary to stress shielding; increased incidence of infection,
      extrusion, and palpability, especially in regions with minimal soft-tissue
      coverage; and interference with radiological studies and postoperative radiation
      therapy. Biodegradable rigid fixation can easily eliminate a majority of these
      problems because the material provides adequate fixation for a finite interval
      corresponding to bony repair. For this reason, there has been increasing interest
      in developing satisfactory biodegradable plate and screw systems. We tested a
      commercially developed polyglyconate plate and screw system to stabilize
      zygomatic osteotomies in a nonhuman primate model before embarking on clinical
      trials. In this experimental model, the stabilized segments revealed satisfactory
      alignment; in the control animals, the bony fragments became significantly
      displaced. This polyglyconate plate and screw system appears to have a promising
      role in the surgical correction of craniomaxillofacial deformities in humans, and
      clinical testing should commence.

PMID- 9020736
TI  - Firearm injuries in maxillofacial region reconstructive surgery.
AB  - Firearms induce severe morphological and structural alterations on both soft and
      bony tissues of the face. It is therefore essential to restore their previous
      functionality. In our experience, maxillofacial lesions due to firearm shooting
      must be divided, from a locational point of view, into those lesions involving
      the upper third, those involving the medium third, and those involving the lower
      third of the face. Lesions of soft and bony tissues must be evaluated precisely
      through instrumental diagnostic examinations and axial and coronal computed
      tomographic projection, preferably with a three-dimensional construction, to be
      able to restore the previous functional integrity of the maxillofacial region. At
      a subsequent surgical time, it may be necessary to plan aesthetic corrections for
      recovery of the previous facial harmony.

PMID- 9020737
TI  - Resorbable coupling fixation in craniosynostosis surgery: experimental and
      clinical applications.
AB  - The use of resorbable bone fixation devices composed of a copolymer of
      polyglycolic acid and polylactic acid were investigated in an animal model as
      well as in human application. We used resorbable plates and metallic microscrews
      in immature rabbits; plating of the coronal suture resulted in complete device
      resorption and increased interscrew distances (i.e., growth across the suture)
      after 8 postoperative months. In 20 infants with calvarial deformities, thin,
      straight resorbable plates were used for skeletal fixation after osteotomies and
      repositioning. A total of 231 fixation devices were implanted without
      complications after 12 postoperative months. These encouraging results have led
      to further clinical application in craniosynostosis deformities.

PMID- 9020738
TI  - The infant skull in Pfeiffer's syndrome.
AB  - A review of Pfeiffer's syndrome patients presenting in infancy identifies
      characteristic patterns of onset and progression of premature sutural fusion.
      Classic Pfeiffer's syndrome manifests symmetrical bicoronal synostosis; all other
      sutures are normal. The remaining patients, with a more extreme phenotypic
      expression, have superimposed on bicoronal synostosis progressive involvement of
      other cranial sutures, frequent hydrocephalus and craniolacunae, suggesting
      craniostenosis and intracranial hypertension. Although similar in clinical
      features and outcome, these patients have been subgrouped according to the
      presence or absence of a cloverleaf skull anomaly.

PMID- 9020739
TI  - Commentary on PAIT effect.

PMID- 9020740
TI  - Osteogenic potential of infant dural grafts in different recipient beds.
AB  - An experimental study in adult rats was designed to test whether infant dura,
      when transplanted as an isograft to different recipient beds, can maintain its
      osteogenic potential. There was bone regeneration in more than 50% of the defects
      in all animals in which infant dura was present. There was minimal bone
      regeneration in defects in which adult dura remained alone and in which the dural
      defect repaired with adult dural graft. Ectopic bone did not form on the
      abdominal fascia or in the abdominal muscles from either infant or adult dural
      transplantation.

PMID- 9020741
TI  - Pneumocephalus caused by fistulas of the mastoid air cells treated with a
      temporoparietal fascial flap.
AB  - Using a temporoparietal fascial flap and hydroxyapatite ceramics, we treated a
      patient for complications after a neurosurgical operation for glossopharyngeal
      neuralgia. These consisted of pneumocephalus and cerebrospinal fluid rhinorrhea
      resulting from fistulas of mastoid air cells associated with a subcutaneous dead
      space. By means of the temporoparietal fascial flap, we were able to fill the
      dead space and reinforce the repaired dural and mastoid lesion as well.
      Hydroxyapatite ceramics were also useful for closing the mastoid air cell
      fistulas.

PMID- 9020742
TI  - Bilateral cleft lip and palate associated with agenesis of the hand and distal
      forearm.
AB  - We report on a child who was born with an incomplete bilateral cleft lip and
      palate associated with agenesis of the left hand and distal forearm. No other
      anomalies were noted. The patient was the first child of a term pregnancy with a
      negative family history, and the mother took no prenatal medications.
      Ultrasonogram performed at 34 weeks' gestational age failed to detect any
      congenital anomalies. Thorough genetics evaluation, including chromosome
      analysis, showed no further abnormalities; the birth defects were believed to be
      nonsyndromic. To our knowledge, the association of bilateral cleft lip and palate
      with agenesis of the upper extremity has not been previously reported. Moreover,
      it is important to note that a prenatal ultrasonogram, even when performed late
      in the third trimester, may fail to detect these significant congenital
      anomalies.

PMID- 9020743
TI  - Percutaneous endoscopic sinus surgery for frontal sinusitis or a cyst.
AB  - Using percutaneous endoscopic surgery, we achieved good results in patients with
      frontal sinus cyst. The surgical procedure is described and discussed. The
      endoscopic system consisted of a needle-shaped rigid fiberscope (direct-vision
      and angle-vision types [30 degrees, 90 degrees]) 1.7 mm in diameter with a light
      source. A small incision was made at the eyebrow, the sinus was cleaned, and an
      opposite hole was made through the existing wound. This procedure permitted less
      invasive surgery under direct view of the surgical field compared with
      conventional percutaneous transnasal frontal sinus procedures. Postoperative
      patency of the sinus was also satisfactory. This percutaneous endoscopic
      procedure was designed for surgical maneuvers in the frontal sinus through a
      small, 3- to 5-mm incision. This technique is considered effective for the
      treatment of inflammatory disorders of the frontal sinus caused by positional
      abnormalities after trauma or recurrence after conservative transnasal surgery.

PMID- 9020745
TI  - Endoscopic nasofrontal disjunction.
AB  - Disjunction of the nasofrontal junction was performed under endoscopic control in
      three patients who underwent a monoblock nasal framework osteotomy and two
      patients who underwent a modified Le Fort type II osteotomy through a small
      midscalp incision, a stub wound at the root of the nose, and an
      intercartilaginous incision. A bilateral intercartilaginous incision and nasal
      root stub wound were used in one case. An osteotomy of the nasal root was
      performed using a specially designed detachable osteotomy consisting of a thin
      staff and large handle. The end of the staff was inserted through the access
      incision and pulled through a stub wound created in the nasal root. The staff was
      then attached to the handle, and the osteotomy was performed under endoscopic
      control. This approach minimizes the surgical scar, the area of the subperiosteal
      dissection, and postoperative swelling of the face, in comparison with the
      coronal approach.

PMID- 9020746
TI  - Endoscopic excision of forehead osteoma.
AB  - The endoscopic excision of a forehead osteoma is reported. This method leaves no
      scars in the forehead, results in positive excision of the tumor, and involves no
      complications such as nerve damage or vascular injury with direct endoscopic
      vision. It is considered to be an excellent procedure with respect to cosmetic
      results.

PMID- 9020744
TI  - Aesthetic and functional reconstruction in intraosseus hemangiomas of the zygoma.
AB  - The incidence of intraosseus hemangiomas is very low. The mandible, the zygoma,
      the maxilla, and the frontal bone are the most frequent areas of localization in
      the craniomaxillofacial region. Surgery, without preoperative embolization, is
      always the best treatment for intraosseus hemangiomas of the zygoma. The radical
      removal of the tumor frequently causes a contour defect that has to be corrected.
      Calvarial grafts provide a good solution to the problem of reconstruction of bone
      loss. They are easy to prepare, near to the implant zone, and they do not require
      changes in the patient's position during the operation. The implants fixed by
      micro- and minifixation systems provide a good functional and aesthetic result.
      We, after a review of the literature on intraosseus hemangiomas of the
      craniomaxillofacial region, report two cases of intraosseus hemangiomas of the
      zygoma in which removal of the tumor and reconstruction with calvarial grafts
      have been performed.

PMID- 9020747
TI  - Approaching the zygoma with an endoscope.
AB  - A hemicoronal or coronal incision is required in combination with a buccal
      incision to expose the zygoma, including zygomatic process of the temporal bone,
      and lateral orbital rim under direct visualization. An endoscope was used to
      expose zygoma in selected cases to reduce the length of the incision. The
      zygomatic bone and arch were exposed and corrected using an endoscope in eight
      cases of zygomatic fracture and one case of zygomatic reduction through a small
      incision just behind the temporal hairline together with a buccal incision. The
      results obtained were satisfactory with no complications. Clear, magnified
      endoscopic visualization made it possible to correct some deformities located in
      this area without using a coronal incision. Endoscopic procedures result not only
      in dramatically less postoperative scarring because of the small access
      incisions, but they also cause less damage to vascular and lymphatic circulation
      and, therefore, are associated with less postoperative edema. However, the
      fixation of the zygomatic arch using the percutaneous method with an endoscope is
      a complicated procedure that requires more time than conventional procedures.

PMID- 9020748
TI  - Resolving controversies related to plate and screw fixation in the growing
      craniofacial skeleton.

PMID- 9020749
TI  - Public health ... it's the healthiest state in the country.

PMID- 9020750
TI  - Public health ... let's talk about s-e-x.

PMID- 9020751
TI  - Education ... one doctor's technological advance is another's lost educational
      opportunity.

PMID- 9020752
TI  - Continuum of care ... can the Department of Veterans Affairs compete and beat for
      profit hospitals?

PMID- 9020753
TI  - Insurance ... men run up fewer, but bigger, health care bills.

PMID- 9020754
TI  - Litigation ... 4,600 hospitals nationwide had overcharged Medicare.

PMID- 9020755
TI  - Policy ... Health Care Finance Administration is restructuring.

PMID- 9020756
TI  - Benchmarking guide. Data rules.

PMID- 9020757
TI  - Buyer's remorse? After a shopping spree, Integrated Health must start living up
      to its name.

PMID- 9020758
TI  - Information systems. Ghost in the machine.

PMID- 9020759
TI  - Human resources. Aiming for ... no vacancy.

PMID- 9020760
TI  - Technology. Phone first.

PMID- 9020761
TI  - Physicians. Home-grown HMOs.

PMID- 9020762
TI  - HospitalPulse. August 1996.

PMID- 9020763
TI  - Structure of bacterial luciferase beta 2 homodimer: implications for flavin
      binding.
AB  - The crystal structure of the beta 2 homodimer of Vibrio harveyi luciferase has
      been determined to 2.5 A resolution by molecular replacement. Crystals were grown
      serendipitously using the alpha beta form of the enzyme. The subunits of the
      homodimer share considerable structural homology to the beta subunit of the alpha
      beta luciferase heterodimer. The four C-terminal residues that are disordered in
      the alpha beta structure are fully resolved in our structure. Four peptide bonds
      have been flipped relative to their orientations in the beta subunit of the alpha
      beta structure. The dimer interface of the homodimer is smaller than the
      interface of the heterodimer in terms of buried surface area and number of
      hydrogen bonds and salt links. Inspection of the subunits of our structure
      suggests that FMNH2 cannot bind to the beta 2 enzyme at the site that has been
      proposed for the alpha beta enzyme. However, we do uncover a potential FMNH2
      binding pocket in the dimer interface, and we model FMN into this site. This
      proposed flavin binding motif is consistent with several lines of biochemical and
      structural evidence and leads to several conclusions. First, only one FMNH2 binds
      per homodimer. Second, we predict that reduced FAD and riboflavin should be poor
      substrates for beta 2. Third, the reduced activity of beta 2 compared to alpha
      beta is due to solvent exposure of the isoalloxazine ring in the beta 2 active
      site. Finally, we raise the question of whether our proposed flavin binding site
      could also be the binding site for flavin in the alpha beta enzyme.

PMID- 9020764
TI  - Probing intermolecular main chain hydrogen bonding in serine proteinase-protein
      inhibitor complexes: chemical synthesis of backbone-engineered turkey ovomucoid
      third domain.
AB  - Intermolecular main chain H-bonding networks are frequently encountered at the
      interface of complexes of protein proteinase inhibitors and their cognate
      enzymes. Studies of X-ray crystal structures of many protein inhibitors complexed
      with serine proteinases have revealed that the amide NH group of the P1 residue
      in the inhibitor donates an H-bond to the carbonyl C = O group of Ser214 and
      Ser195 Oy in the enzyme (Ser125 and Ser221 in subtilisins, respectively). To
      probe the energetic contribution of this backbone H-bond in the complexes of
      OMTKY3 with several serine proteinases, native chemical ligation was used for the
      total synthesis of a backbone-engineered analog of OMTKY3, in which the amide
      peptide bond between Thr17 (P2) and Leu18 (P1) was replaced by an ester bond,
      i.e., -CONH-to-COO-. This chemical "mutation" effectively eliminated the backbone
      H-bond donated by the NH group of Leu18. By measuring association equilibrium
      constants for synthetic wild-type OMTKY3 and the backbone-engineered ester analog
      interacting with a panel of six serine proteinases, we have determined that the
      P1 NH-->O substitution weakens the binding of OMTKY3 to its cognate enzymes by an
      average of 15-fold, i.e., 1.5 +/- 0.3 kcal/mol. These results place a
      quantitative value on the contribution of the intermolecular backbone H-bond in
      enzyme-inhibitor recognition.

PMID- 9020765
TI  - Isolated calcium-binding loops of EF-hand proteins can dimerize to form a native
      like structure.
AB  - Helix-loop-helix fragments of EF-hand proteins are known to dimerize in solution,
      re-producing the characteristic structure of native protein domains [Shaw, G.S.,
      Hodges, R.S., & Sykes, B. D. (1990) Science 249, 280-283]. In this paper we
      present evidence that isolated calcium-binding loops can also dimerize, when
      saturated with lanthanide ions, interacting with each other in a similar way as
      do loops in intact proteins. A synthetic analogue of calcium binding loop III of
      calmodulin, AcDKDGDGYISAAE-NH2, has been studied by 1H NMR spectroscopy. For the
      La(3+)-saturated peptide, concentration dependent broadenings and shifts of
      certain signals have been observed indicating dimerization process of
      intermediate rate on the NMR time scale. Analysis of signal shape and position of
      the Tyr7 ring protons as a function of concentration makes it possible to
      determine the association and dissociation rate constants of the process for
      various temperatures within the range of 10-80 degrees C. The dimerization
      constant changes according to van't Hoff relationship with delta S = 233 J/mol.K
      and delta H = 62 kJ/mol. A distance of 11.4 +/- 0.4 A between the ions
      coordinated by dimer molecules has been determined by measurements of Tb(3+)-
      >Ho3+ luminescence energy transfer. This value suggests that the dimer structure
      is similar to that of two-loop structural elements in native EF-hand proteins.
      From a thermodynamic cycle it can be shown that La3+ ion binding to the peptide
      dimers must be highly cooperative. Therefore, cooperativity of ion binding to
      domains of EF-hand proteins is, at least partly, due to local interactions
      between binding loops.

PMID- 9020766
TI  - Contribution of the hydrophobic effect to the stability of human lysozyme:
      calorimetric studies and X-ray structural analyses of the nine valine to alanine
      mutants.
AB  - To clarify the contribution of the hydrophobic effect to the conformational
      stability of human lysozyme, a series of Val to Ala mutants were constructed. The
      thermodynamic parameters for the denaturation of these nine mutant proteins were
      determined using differential scanning calorimetry (DSC), and the crystal
      structures were solved at high resolution. The denaturation Gibbs energy (delta
      delta G) and enthalpy (delta delta H) values of the mutant proteins ranged from
      +2.2 to- 6.3 kJ/mol and from +7 to -17 kJ/mol, respectively. The structural
      analyses showed that the mutation site and/or the residues around it in some
      proteins shifted toward the created cavity, and the substitutions affected not
      only the mutations site but also other parts far from the site, although the
      structural changes were not as great. Correlation between the changes in the
      thermodynamic parameters and the structural features of mutant proteins was
      examined, including the five Ile to Val mutant human lysozymes [Takano et al.
      (1995) J. Mol. Biol. 254, 62-76]. There was no simple general correlation between
      delta delta G and the changes in hydrophobic surface area exposed upon
      denaturation (delta delta ASAHP). We found only a new correlation between the
      delta delta G and delta delta ASAHP of all of the hydrophobic residues if the
      effect of the secondary structure propensity was taken into account.

PMID- 9020768
TI  - Identification of a novel 97 kDa endonuclease capable of internucleosomal DNA
      cleavage.
AB  - The two steps of DNA digestion seen in apoptotic cells were recreated in nuclei
      isolated from 5123tc rat hepatoma cells. The initial DNA cleavage, into high
      molecular weight fragments (300-50 kb), was stimulated by magnesium ions alone,
      whereas the second step required both calcium and magnesium ions and produced the
      ladder of oligonucleosomes. Endonucleolytic activities involved in both steps of
      DNA cleavage could be separated under appropriate conditions since the magnesium
      modulated activity was tightly bound to the chromatin whereas the
      calcium/magnesium-dependent internucleosomal cleaving activity was easily
      extractable with a low ionic strength buffer. This calcium/ magnesium-dependent
      activity was attributed to a novel 97 kDa endonuclease which was also activated
      by manganese and cobalt and inhibited by millimolar concentrations of zinc,
      consistent with the properties ascribed to the apoptotic endonuclease.
      Furthermore, this activity became resistant to extraction with a low salt buffer
      in nuclei of apoptotic cells. Isoelectrofocusing revealed that the p97 protein
      existed in multiple forms of different isoelectric points (pI range 4.6-5.0),
      indicative of its postranslational modification. The p97 enzyme was present
      constitutively in a variety of cultured cells and rat tissues. It was active over
      a broad range of pH (6-9), but it was inactivated by reducing agents. In vitro,
      it displayed both endo- and exonucleolytic activities, and it was capable of both
      single- and double-stranded DNA cleavage. Rabbit polyclonal anti-p97 antibodies
      were generated and used to further distinguish this protein from other known
      cellular nucleases, namely, DNases I and II.

PMID- 9020767
TI  - Phosphotransfer site of the chemotaxis-specific protein kinase CheA as revealed
      by NMR.
AB  - Bacterial chemotaxis involves autophosphorylation of a histidine kinase and
      transfer of the phosphoryl group to response regulators to control flagellar
      rotation and receptor adaptation. The phosphotransfer domain, CheA1-134, of the
      chemotaxis-specific histidine autokinase CheA from Escherichia coli contains the
      site of phosphorylation, His48, and two other histidine residues, His26 and
      His67. Two-dimensional 1H-15N NMR techniques were applied to characterize the
      protonation states of these histidine residues and to evaluate the structural
      changes in the domain that occur upon phosphorylation of His48. The pKa of His48
      was determined to be 7.8 (in 50 mM NaPO4 buffer at 30 degrees C). At high pH, its
      imidazole ring exists primarily as the normally unfavored N delta 1H tautomer,
      suggesting hydrogen bond formation to the ring nitrogen atom(s) to stabilize this
      state. The pKa values and predominant tautomeric states of the imidazole rings of
      His26 (pKa approximately 7.1, N epsilon 2H tautomer) and His67 (pKa approximately
      6.5, N delta 1H tautomer) were also determined. His48 of CheA1-134 and CheA1-233
      was phosphorylated by full-length CheA. The phosphorylation site was confirmed to
      be the N epsilon 2 position in the imidazole ring. Phosphorylation of His48 only
      results in small changes in the amide 1H and 15N chemical shifts of a few
      residues from helices B and C, suggesting that only very small changes in
      structure are associated with phosphorylation of the phosphotransfer domain of
      CheA. These residues occupy a small surface area of the helix bundle and form the
      active site of the protein. At the active site, in addition to His48, residues
      Gly52, His67, and Glu70 are conserved in the CheA homologous phosphotransfer
      domains from 10 different organisms. Sequence comparison of these CheA homologs
      suggest that the phosphotransfer domains likely fold in a similar helix-bundle
      structure and the structural features at the active site are well-conserved.

PMID- 9020769
TI  - Purification, characterization, gene cloning, and expression of Saccharomyces
      cerevisiae redoxyendonuclease, a homolog of Escherichia coli endonuclease III.
AB  - Saccharomyces cerevisiae redoxyendonuclease (Scr), a homolog of Escherichia coli
      endonuclease III, was purified from yeast deficient in the major
      apurinic/apyrimidinic endonuclease, Apnl. Studies of this highly purified
      preparation of Scr have revealed a number of similarities between this protein
      and endonuclease III as well as provided further evidence for a common mechanism
      of action for this class of DNA glycosylase/AP lyases. We have employed a
      sensitive and specific assay for Scr which utilizes oligonucleotide substrates
      containing a single 5,6-dihydrouracil base lesion or an abasic site. These
      substrates were utilized to investigate the mode of action of Scr on damaged DNA
      and to compare the kinetic properties of the yeast enzyme with its E. coli
      counterpart. Furthermore, we have identified two distinct genes, SCR1 and SCR2,
      which encode highly homologous proteins with similar activities in yeast.
      Analysis of the deduced amino acid sequences of SCR1 and SCR2 suggests that S.
      cerevisiae possesses two similar enzymes encoded on separate chromosomes: one
      which bears an Fe-S binding motif, while the other does not. The potential
      biological roles of these two forms of Scr are discussed.

PMID- 9020770
TI  - Zinc site redesign in T4 gene 32 protein: structure and stability of cobalt(II)
      complexes formed by wild-type and metal ligand substitution mutants.
AB  - Phage T4 gene 32 protein (gp32) is a zinc metalloprotein which binds
      cooperatively and preferentially to single-stranded nucleic acids and functions
      as a replication and recombination accessory protein. Zn(II) coordination by gp32
      employs a His-Cys3 metal ligand donor set derived from the His64-X12-Cys77-X9
      Cys87-X2-Cys90 sequence in the ssDNA-binding core domain of the molecule.
      Crystallographic studies reveal that His64 and Cys77 are derived from two
      independent beta-strands within a distorted three-stranded beta-sheet and are
      relatively more buried from solvent than are Cys87 and Cys90, which are
      positioned immediately before and within, respectively, an alpha-helix. In an
      effort to understand the origin of the stability of the metal complex, we have
      employed an anaerobic optical spectroscopic, competitive metal binding assay to
      determine the coordination geometry and association constants (Ka) for the
      binding of Co(II) to wild-type gp32 and a series of zinc ligand substitution
      mutants. At pH 7.5, 25 degrees C, wild-type gp32 binds Co(II) with a Ka
      approximately 1 x 10(9) M-1. Competition experiments reveal that Ka for Zn(II) is
      3.0 (+/-1.0) x 10(11) M-1. We find that all non-native metal complexes retain
      tetrahedral or distorted tetrahedral coordination geometry but are greatly
      destabilized in a manner essentially of whether a new protein-derived
      coordination bond is formed (e.g., in H64C gp32) or not. Co(II) binding isotherms
      obtained for three His64 substitution mutants, H64C, H64D, and H64N gp32s,
      suggest that each mutant forms a dimeric Cys4 tetrathiolate intermediate complex
      at limiting [Co(II)]f, each then rearranges at high [Co(II)]f to form a
      monomolecular site of the expected geometry and Ka approximately 1 x 10(4) M-1.
      Like the His64 mutants, C77A gp32 appears to form at least two types of complexes
      over the course of a Co(II) titration: one with octahedral coordination geometry
      formed at low [Co(II)]f, with a second tetrahedral or five-coordinate site formed
      at higher [Co(II)]f. Apo C87S and C90A gp32s, in contrast, each form a single
      complex at all [Co(II)]f, consistent with Cys2-His-H2O tetrahedral geometry of Ka
      approximately (1-2) x 10(5) M-1. These studies reveal that the local protein
      structure restricts accommodation of a non-native metal complex in a ligand
      specific manner. The implications of this work for de novo design of zinc
      complexes in proteins are discussed.

PMID- 9020771
TI  - Antisense gene inhibition by C-5-substituted deoxyuridine-containing
      oligodeoxynucleotides.
AB  - Antisense oligodeoxynucleotides (ODNs) are capable of inhibiting gene expression
      via a RNase H mechanism in which the complementary RNA is degraded by RNase H. C
      5 propyne dU phosphorothioate ODNs bind selectively and with high affinity to RNA
      within cells leading to potent antisense inhibition of RNA translation. The
      effect that increasing steric bulk of C-5-substituted deoxyuridine analogs has on
      affinity for RNA and ability to inhibit gene expression is discussed. The
      relative binding affinity was measured by thermal denaturation (Tm) analysis, and
      antisense activity was determined by inhibition of SV40 T-antigen (TAg)
      expression in CV1 cells. The results show that antisense activity is not directly
      correlated to Tm measurements. In vitro analysis (RNase H cleavage, on-rates, and
      off-rates) and pre-formed ODN/RNA experiments indicate that RNase H activity and
      intracellular dissociation appear to be major determinants of the antisense
      potency of the various substituted ODNs. The results of our analysis point to the
      unique ability of C-5 propyne dU ODNs to selectively bind to RNA within cells and
      activate cleavage of RNA by RNase H leading to potent inhibition of gene
      expression.

PMID- 9020772
TI  - The origins of nonphotochemical quenching of chlorophyll fluorescence in
      photosynthesis. Direct quenching by P680+ in photosystem II enriched membranes at
      low pH.
AB  - In most plants and algae, a down-regulation of photosynthesis under "excess"
      light conditions occurs which is associated with a quenching of chlorophyll a
      fluorescence. This nonphotochemical quenching of chlorophyll a fluorescence most
      likely arises from a mechanism which protects photosystem II from excessive
      excitation and resulting photoinhibition. In this report, nonphotochemical
      quenching of variable chlorophyll a fluorescence was induced by low pH in
      photosystem II enriched spinach thylakoid membranes. The origin of quenching was
      investigated with picosecond fluorescence decay spectroscopy in samples suspended
      in buffers ranging from pH 6.5 to pH 4.0. The yield of a relatively slow
      (approximately 1.5 ns) fluorescence decay process associated with the photosystem
      II reaction center decreased with decreasing pH. There were no significant
      changes in the yield of faster decay components associated with photosystem II
      antenna chlorophyll a processes. These results suggest a reaction center based
      rather than antenna chlorophyll based mechanism for nonphotochemical quenching in
      these preparations. Measurements of the photosystem II absorption cross section
      revealed no decrease in the functional antenna size at low pH which also supports
      a reaction center quenching mechanism. The kinetics of electron transfer in
      photosystem II were investigated using a pump probe spectrometer which measured
      simultaneously the flash-induced absorbance change at 820 nm (formation of
      oxidized photosystem II reaction center pigment, P680+) and the variable
      fluorescence yield (formation of reduced photosystem II, electron acceptor, QA-).
      A large increase in the lifetime of P680+ at low pH was correlated with
      fluorescence quenching. After flash excitation of photosystem II the loss of
      fluorescence quenching occurred with the same kinetics as the reduction of P680+.
      In conflict with reaction center based quenching mechanisms based on charge
      recombination between P680+ and QA-, the oxidation rate of QA- was unaffected by
      low pH and under all conditions occurred at a slower rate than the reduction of
      P680+. Our data are discussed in terms of a model for low pH dependent
      nonphotochemical quenching in photosystem II based on direct quenching by P680+.

PMID- 9020773
TI  - Thermodynamic properties of a conformationally constrained intramolecular DNA
      triple helix.
AB  - We describe the thermodynamic properties of an intramolecular triple helix with
      two all-thymine linker loops in which the Hoogsteen strand is covalently
      crosslinked to the underlying Watson-Crick hairpin duplex by means of a disulfide
      bridge. We compare these properties to those of the corresponding intramolecular
      triplex without the disulfide crosslink. Optical and calorimetric measurements
      reveal that the uncrosslinked parent triplex melts in a biphasic manner above pH
      6, with the initial triplex to duplex transition (Hoogsteen strand release)
      occurring at lower temperatures than subsequent melting of the hairpin helix. By
      contrast, crosslinking increases the thermal stability of the Hoogsteen
      transition such that the triplex and underlying hairpin duplex melt as a single
      transition under all conditions studied. Model independent thermodynamic data
      obtained by differential scanning calorimetry reveals the crosslink-induced
      increase in triplex thermal stability corresponds to a free energy stabilization
      of about 3 kcal/mol, with this stabilization being entirely entropic in origin.
      In other words, the crosslink is enthalpically neutral, but nevertheless, induces
      a triplex stabilization of 3 kcal/mol due to a reduction in the entropy change
      associated with triplex melting. In an effort to define the origin(s) of this
      entropic impact, we measured the pH and ionic strength dependence of the melting
      transitions. From a comparison of the melting transitions at different pH values
      and ionic strengths, we estimate that 0.4 more protons are associated with the
      crosslinked triplex state than with the uncrosslinked triplex, and 1.3 fewer
      counterions are released on melting the crosslinked triplex. We discuss how such
      crosslink-induced changes in proton binding and counterion release, in
      conjunction with potential changes in hydration and conformational freedom, could
      combine to give rise to the observed changes in entropy.

PMID- 9020774
TI  - Specificity of aminoglycoside binding to RNA constructs derived from the 16S rRNA
      decoding region and the HIV-RRE activator region.
AB  - Aminoglycoside antibiotics can bind to many different types of RNA molecules. It
      was of interest to determine the nature of the selectivity of binding of
      aminoglycosides to important, biologically relevant RNA targets. Fluorescence
      anisotropy methods were developed to quantitatively measure aminoglycoside
      affinities to constructs of the HIV-1 RRE transcriptional activation region and
      the prokaryotic rRNA decoding region which is the natural antibacterial target of
      the aminoglycosides. A fluorescent analog of Rev34-50 (Fl-Rev34-50) was prepared
      and shown by fluorescence anisotropy measurements to bind to the HIV-1 RRE region
      with a stoichiometry of 1 and a dissociation constant of 7.6 nM. RRE RNA is a
      target for the arginine rich Rev protein, and the binding is known to be mimicked
      by Rev34-50. The binding is driven by a strongly negative enthalpic term.
      Aminoglycosides compete with Fl-Rev34-50 binding and competition experiments with
      semisynthetic aminoglycosides and neomycin B and tobramycin show binding
      affinities in the 1-2 microM range. The binding of aminoglycosides to this
      construct is thus not highly selective. A prokaryotic rRNA construct was also
      prepared and shown to bind a fluorescent dye labeled derivative of the antibiotic
      paromomycin (CRP) stoichiometrically with a dissociation constant of 0.16 microM.
      Competition experiments with other aminoglycosides showed binding in the
      micromolar range, with limited specificity for aminoglycoside type, suggesting
      that much of the aminoglycoside molecule is not involved in binding. The
      relatively modest specificity in the binding of aminoglycoside described above is
      to be contrasted to the subnanomolar affinities and specificity of aminoglycoside
      binding found using in vitro selected RNA molecules (Wang et al., 1996).

PMID- 9020775
TI  - Why is CMP-ketodeoxyoctonate highly unstable?
AB  - CMP-ketodeoxyoctonate (CMP-KDO) and analogs, including CMP-5-deoxy-5-fluoro-KDO,
      CMP-5-deoxy-KDO, and CMP-5-epi-KDO, were prepared from CTP and the corresponding
      KDO sugars catalyzed by CMP-KDO synthetase. These analogs were found to be much
      more stable than CMP-KDO (t1/2 = 0.57 h) yet less stable than CMP-sialic acid
      (t1/2 = 151 h). Fluorination at the 5-position of CMP-KDO has a 200-fold enhanced
      stability compared to the 156-fold enhancement for the 3R-fluoro analog, probably
      due to the loss of H-bonding interactions (for the 5-F derivative) and the cause
      of remote inductive effect (for the 3- and the 5-F analogs) on the glycosidic
      cleavage. Hydrolysis of CMP-KDO is perhaps facilitated by an intramolecular
      hydrogen bond from the 5-OH group with the phosphate oxygen as demonstrated by
      the 3-5-fold enhanced stability of CMP-5-epi-KDO and CMP-5-deoxy-KDO compared to
      CMP-KDO and by molecular modeling studies of water-solvated CMP-KDO. Hydrolysis
      of CMP-KDO also was found to be subject to a substantial solvent isotope effect
      (kH/kD = 2.7), which is significantly different from the reported solvent isotope
      effect for the hydrolysis of sialyglycosides (kH/kD = 0.86) and dependent on both
      buffer and magnesium ion concentrations. Considering these results and molecular
      modeling studies, it is proposed that the hydrolysis of CMP-KDO under neutral
      conditions proceeds through a glycosidic cleavage which occurs at the
      electronically favorable twist-boat conformation, facilitated by intramolecular H
      bonding interaction of the 4-, 5- and 7- (or 8-) OH groups and the phosphate
      oxygen and by the leaving group magnesium ion complexation.

PMID- 9020776
TI  - A single amino acid substitution, Gly117His, confers phosphotriesterase
      (organophosphorus acid anhydride hydrolase) activity on human
      butyrylcholinesterase.
AB  - The G117H mutant of human butyrylcholinesterase (EC 3.1.1.8) was expressed in
      Chinese hamster ovary cells. Substitution of Gly 117 with His to make the G117H
      mutant endowed butyrylcholinesterase with the ability to catalyze the hydrolysis
      of organophosphate esters. G117H was still able to hydrolyze butyrylthiocholine,
      benzoylcholine, and o-nitrophenyl butyrate, but in addition it had acquired the
      ability to hydrolyze the antiglaucoma drug echothiophate and the pesticide
      paraoxon. Wild-type butyrylcholinesterase was irreversibly inhibited by
      echothiophate and paraoxon, but G117H regained 100% activity within 2-3 min
      following reaction with these compounds. On a polyacrylamide gel, the same bands
      that stained for activity with butyrylthiocholine also stained for activity with
      echothiophate. G117H is the only enzyme known that hydrolyzes echothiophate.
      Diethoxyphosphorylated G117H aged with a half-time of 5.5 h, a rate 600 times
      slower than the rate of hydrolysis. Echothiophate and paraoxon were hydrolyzed
      with the same kcat of 0.75 min-1. This calculates to a rate acceleration of
      100,000-fold for hydrolysis of echothiophate and paraoxon by the G117H mutant
      compared to the nonenzymatic rate.

PMID- 9020777
TI  - Kinetic characterization of wild-type and S229A mutant MurB: evidence for the
      role of Ser 229 as a general acid.
AB  - X-ray derived structural data predicted that serine 229 was positioned to act as
      a proton donor to the developing C2 carbanion during the reduction of enolpyruvyl
      UDP-N-acetylglucosamine catalyzed by the bacterial peptidoglycan biosynthetic
      flavoenzyme MurB. To investigate this effect, a mutant where serine 229 was
      replaced by alanine was constructed and purified. Kinetic analysis of the two
      half-reactions for the mutant enzyme revealed a 9-fold decrease in the reduction
      of EFlox by NADPH and a dramatic 10(7)-fold decrease in the reoxidation of EFlred
      with the enolpyruvyl substrate. In addition, studies of S229A with the substrate
      analog, (E)-enolbutyryl-UDP-N-acetylglucosamine, showed a striking bias of the
      partitioning toward formation of the (Z) geometric isomer as opposed to formation
      of the reduced product UDP-methylmuramic acid, which was the predominant product
      in wild-type MurB. These studies provide evidence for the proposed role of this
      active-site serine as a general acid catalyst.

PMID- 9020778
TI  - X-ray crystal structures of the S229A mutant and wild-type MurB in the presence
      of the substrate enolpyruvyl-UDP-N-acetylglucosamine at 1.8-A resolution.
AB  - MurB catalyzes the second committed step in the synthesis of peptidoglycan, a key
      component of the bacterial cell wall. The crystal structures of both a S229A
      mutant and wild-type MurB in the presence of the substrate enolpyruvyl-UDP-N
      acetylglucosamine were solved and refined at 1.8 A resolution. The single point
      mutation of residue 229 from serine to alanine eliminated a hydroxyl group which
      has previously been proposed to play a critical role as a proton donor during the
      second half-reaction of MurB, namely, reoxidation of FADH2 and reduction of the
      enolpyruvyl substrate. The mutation also resulted in the loss of the water
      molecule-hydrogen bonded to the serine hydroxyl in the wild-type structure
      changing the hydrogen-bonding network with in the active site. Comparison of the
      wild-type and S229A mutant structures confirms that the dramatic kinetic defect
      of an approximately 10(7)-fold decrease observed for the Ser 229 Ala mutant in
      the second half-reaction [Benson, T.E., Walsh, C.T., & Massey, V. (1997)
      Biochemistry 36, 796-805] is a direct result of the loss of the serine hydroxyl
      moiety rather than other nonspecific active-site changes or general structural
      defects.

PMID- 9020779
TI  - Spectroscopic properties of Escherichia coli UDP-N-acetylenolpyruvylglucosamine
      reductase.
AB  - Purified uridine diphosphate N-acetylenolpyruvylglucosamine reductase (E.C.
      1.1.1.158) was analyzed by circular dichroism (CD) and UV-visible spectroscopy to
      establish the spectral properties of its tightly bound flavin adenine
      dinucleotide (FAD) cofactor. The polypeptide backbone displayed a single circular
      dichroic minimum at 208 nm and a single maximum at 193 nm. The CD spectrum of
      bound flavin exhibited a single major negative Cotton peak at 364 nm and two
      minor negative Cotton peaks at 464 and 495 nm. The protein was reversibly
      unfolded in 9.8 M urea and refolded in buffer in the presence of excess FAD. The
      refolded enzyme incorporated FAD and catalyzed full activity. The bound FAD
      displayed an absorption maximum at 464 nm with an extinction coefficient of
      epsilon 464 = 11700 M-1 cm-1. Anaerobic reduction with dithionite was complete at
      1 equiv. Anaerobic reduction with nicotinamide adenine dinucleotide phosphate,
      reduced form (NADPH), also was essentially complete at 1 equiv and produced a
      long-wavelength absorbance band characteristic of an FAD-pyridine nucleotide
      charge transfer complex. Photochemical bleaching in the presence of
      ethylenediaminetetraacetic acid (EDTA) followed exponential kinetics. None of the
      anaerobic reductive titrations produced a spectral intermediate characteristic of
      a flavin semiquinone, and all reduced enzyme species could be fully reoxidized by
      oxygen, with full recovery of catalytic activity. Photochemically reduced enzyme
      was reoxidized by titration with either NADP+ or uridine diphospho N
      acetylglucosamine enolpyruvate (UNAGEP). Reoxidation by NADP+ reached a chemical
      equilibrium, whereas reoxidation by UNAGEP was stoichiometric. Binding of NADP+
      or UNAGEP to the oxidized form of the enzyme produced a dead-end complex that
      could be titrated by following a 10-nm red shift in the absorption spectrum of
      the bound FAD. The Kd of NADP+ for oxidized enzyme was 0.7 +/- 0.3 microM and the
      Kd of UNAGEP was 2.7 +/- 0.3 microM. Solvent deuterium isotope effects on binding
      were observed for both NADP+ and UNAGEP, depending on the pH. At pH 8.5, the
      HKd/DKd was 2.2 for NADP+ and 3.9 for UNAGEP. No spectral changes were observed
      in the presence of a 40-fold excess of uridine diphospho N-acetylmuramic acid
      (UNAM) either aerobically or anaerobically. These studies have identified
      spectral signals for five steps in the kinetic mechanism, have indicated that
      product formation is essentially irreversible, and have indicated that hydrogen
      bonding or protonation contributes significantly to ground-state complex
      formation with the physiological substrate.

PMID- 9020780
TI  - Mechanism of human alpha-1,3-fucosyltransferase V: glycosidic cleavage occurs
      prior to nucleophilic attack.
AB  - alpha-1,3-Fucosyltransferase V (FucT V) catalyzes the transfer of 1-fucose from
      the donor sugar guanosine 5'-diphospho-beta-1-fucose (GDP-Fuc) to an acceptor
      sugar. A secondary isotope effect on the fucosyltransfer reaction with guanosine
      5'-diphospho-[1-2H]-beta-1-fucose (GDP-[1-2H]-Fuc) as the substrate was observed
      and determined to be Dv = 1.32 +/- 0.13 and DV/K = 1.27 +/- 0.07. Competitive
      inhibition of FucT V by guanosine 5'-diphospho-2-deoxy-2-fluoro-beta-1-fucose
      (GDP-2F-Fuc) was observed with an inhibition constant of 4.2 microM which
      represents the most potent inhibitor of this enzyme to date. Incubation of GDP-2F
      Fuc with FucT V and an acceptor molecule prior to the addition of GDP-Fuc had no
      effect on the potency of inhibition, indicating that GDP-2F-Fuc is neither an
      inactivator nor a slow substrate. Both the observed secondary isotope effect and
      the inhibition by GDP-2F-Fuc are consistent with a charged, sp2-hybridized,
      transition-state structure. A convenient and efficient synthesis of GDP-[1-2H]
      Fuc and GDP-2F-Fuc and a nonradioactive, fluorescence assay for
      fucosyltransferase activity have been developed.

PMID- 9020781
TI  - Identification of an A2a adenosine receptor domain specifically responsible for
      mediating short-term desensitization.
AB  - In an attempt to delineate the structural requirements necessary for agonist
      induced desensitization, we have stably expressed wild-type and mutant A2a
      adenosine receptors (A2aARs) in Chinese hamster ovary cells and examined the
      effects of agonist pretreatment on adenylyl cyclase activity in subsequently
      isolated membranes. Deletion of 95 amino acids from the carboxyl-terminus of the
      A2aAR, thereby removing 10 potential phosphorylation sites, failed to alter
      radioligand binding, adenylyl cyclase activation, or functional desensitization
      parameters as compared with the wild-type receptor. However, simultaneous
      mutation of Thr 298 and Ser 305 to Ala residues attenuated the desensitization
      observed in response to short-term (30 min) agonist treatment while not blocking
      the ability to desensitize after long-term (24 h) agonist exposure. Individual
      mutation of these residues revealed that mutation of Thr 298 alone was sufficient
      to diminish both short-term desensitization and agonist-stimulated receptor
      phosphorylation. These data suggest that while the majority of the A2aAR carboxyl
      terminus is dispensable with regard to observing functional desensitization, the
      integrity of Thr 298 is essential for observing agonist-stimulated receptor
      phosphorylation and short-term desensitization but not long-term desensitization
      of A2aAR function.

PMID- 9020782
TI  - Interactions of the nicotinic acetylcholine receptor transmembrane segments with
      the lipid bilayer in native receptor-rich membranes.
AB  - Proper ion channel function of the nicotinic acetylcholine receptor (nAChR)
      requires the interaction of the protein with distinct lipid species present in
      the receptor's membrane microenvironment. Two classes of lipid binding sites
      present at the protein-membrane interface have been postulated: annular binding
      sites primarily occupied by phospholipids and non-annular binding sites mainly
      occupied by cholesterol [Jones & McNamee (1988) Biochemistry 27, 2364-2374]. We
      investigated the binding of these lipids to the nAChR and potential dynamics of
      these interactions during events associated with signal transduction by electron
      spin resonance spectroscopy (ESR) using spin-labeled analogues of phospholipids,
      androstane, and stearic acid. Protein-lipid interactions were characterized in
      receptor-rich membranes prepared from Torpedo californica electric tissue
      preserving the native lipid environment of the nAChR. We found a strong
      preference of the receptor for the phosphatidylserine (PS) analogue as compared
      to the other probes. Up to 57% of PS were perturbed by the membrane protein,
      while the fraction of motionally restricted lipid for the other analogues was on
      the order of 30%. After removal of the extramembrane portions of the membrane
      bound receptor, we observed a loss of binding sites for the spin-labeled analogue
      of androstane and for stearic acid, but not for phospholipids and sphingomyelin
      analogues. Our results demonstrate the existence of topologically distinct lipid
      binding sites for different lipid species. In the case of cholesterol,
      extramembrane portions of the receptor are involved, whereas the transmembrane
      segments meet the requirements for the binding of phospholipids. Tyrosine
      phosphorylation of the nAChR did not affect protein-lipid interactions in samples
      of intact nAChR. Similarly, no significant changes were observed in the presence
      of carbamoylcholine at concentrations that caused rapid and quantitative
      desensitization of the nAChR.

PMID- 9020783
TI  - Dependence of the activity of phospholipase C beta on surface pressure and
      surface composition in phospholipid monolayers and its implications for their
      regulation.
AB  - We have examined the influence of surface pressure and phospholipid composition
      on hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2) by phospholipase
      C beta 1 (PLC beta 1) and PLC beta 2 in mixed composition phospholipid
      monolayers. Increasing the monolayer surface pressure from 15 to 36 mN/m reduced
      the rate at which PIP2 was hydrolyzed by PLC beta 1 and PLC beta 2 by 4-6-fold,
      although PLC beta 1 was more active than PLC beta 2, even at high surface
      pressure. Reduced enzyme activity was accompanied by an increase in reaction
      induction times, suggesting that increasing surface pressure reduced the
      penetration rate of the enzymes into the monolayer. Quantitation of interfacial
      enzyme concentration using 35S-labeled PLC beta 1 confirmed that less enzyme was
      associated with the monolayer at higher pressures. The relationship between PLC
      activity and substrate concentration was examined at a single surface pressure of
      30 mN/m. This relationship was not hyperbolic, and increases in the mole
      percentage (mol %) of PIP2 in the monolayer resulted in an upwardly-curving
      increase in PLC activity. Thus, PLC beta 1 activity increased 7-fold and PLC beta
      2 activity increased 4-fold when the mol % of PIP2 in the monolayer increased
      from 17.9% to 29%, increasing further thereafter. Paradoxically, increasing the
      mol % of PIP2 from 0 to 60% was accompanied by a 3-fold decrease in interfacial
      enzyme concentrations. Taken together, these data show that the catalytic
      activity of PLC beta involves some element of penetration of lipid interfaces,
      and suggest that the organization of the substrate facilitates PLC activity,
      giving credence to the substrate theory of interfacial activation of
      phospholipases. We present a hypothesis suggesting that PIP2 molecules coalesce
      into enriched lateral domains which favor PLC beta activity.

PMID- 9020784
TI  - Novel peptide-binding proteins and peptide transport in normal and TAP-deficient
      microsomes.
AB  - Most major histocompatibility complex (MHC) class I-binding peptides are
      translocated by TAP heterodimers, but some enter the ER lumen by alternative
      pathways. To further define mechanisms of peptide handling, we developed a system
      for the analysis of peptide-binding components in the ER membrane and lumen using
      iodinated cross-linkable peptide derivatives. Here we demonstrate that at least
      three proteins bind peptides in the ER lumen. Peptide cross-linking to these
      lumenal proteins can be used as an alternative method to monitor peptide
      transport. TAP and one other protein bind peptides on the cytoplasmic face of the
      ER. The presence of multiple peptide-binding proteins necessitates caution in
      interpreting traditional peptide-binding and transport assays. Finally, we
      demonstrate sequence-specific peptide transport in TAP-deficient cells
      transfected with only rat TAP1.

PMID- 9020785
TI  - Structural dynamics of water and the peptide backbone around the Schiff base
      associated with the light-activated process of octopus rhodopsin.
AB  - Difference Fourier transform infrared spectra were recorded for the formation of
      the photointermediates and isorhodopsin from octopus rhodopsin at low
      temperatures. Analysis was done for H bonding of the Schiff base, internal water
      molecules, and the peptide backbone. The imine hydrogen of the Schiff base was in
      the same H bonding state throughout the photointermediates and the unphotolyzed
      state. In contrast, H bonding of the hydrogen of the water molecule whose oxygen
      might be complexed with the imine hydrogen of the Schiff base was altered upon
      the formation of bathorhodopsin. The same water molecule was in a different H
      bonding state in the subsequent intermediates, lumirhodopsin and mesorhodopsin.
      These intermediates were also characterized by a decrease in the C = N bond order
      of the Schiff base as a reflection of distorted structure around the Schiff base.
      The polar N-H bond in these intermediates could be also ascribed to the Schiff
      base. Some changes in H bonding of water and the perturbation of the polyene
      chain in lumirhodopsin and mesorhodopsin were also observed in isorhodopsin. Acid
      metarhodopsin exhibited extensive changes in the H bonding states of the peptide
      backbone and internal water molecules. A large part of these changes was
      extinguished in alkaline metarhodopsin with the unprotonated Schiff base,
      suggesting interaction of the protonated Schiff base with the peptide backbone
      and intramembrane water molecules in acid metarhodopsin.

PMID- 9020786
TI  - Interaction of estramustine with tubulin isotypes.
AB  - The interaction of the antimitotic agent estramustine with bovine microtubule
      proteins and purified tubulin was investigated. Direct photoaffinity labeling of
      microtubule protein with [14C]estramustine resulted in the labeling of both alpha
      and beta-tubulin, and this was inhibited with unlabeled estramustine in a dose
      dependent manner. [14C]Estramustine was incorporated into both the soluble and
      polymerized forms of tubulin. The affinity constant for estramustine binding to
      tubulin was determined by equilibrium dialysis to be 23 +/- 5 mM. Estramustine
      did not affect [3H]vinblastine binding, and vinblastine had no effect on direct
      labeling with [14C]estramustine. Both rhizoxin and paclitaxel decreased the
      covalent labeling of tubulin with [14C]estramustine in a dose-dependent fashion
      and were noncompetitive inhibitors of the binding of estramustine to tubulin. The
      binding of colchicine to tubulin was not inhibited by estramustine as detected by
      fluorescence and DEAE filter assays. The estramustine binding site on tubulin is
      therefore distinct from that of colchicine and vinblastine and may at least
      partially overlap with the binding site for paclitaxel. In both bovine brain
      microtubules and cytoskeletal proteins from human prostatic carcinoma cells, the
      incorporation of [14C]estramustine into the beta III isotype of tubulin was found
      to occur with a reduced efficiency compared to that of the other beta-tubulin
      isotypes and alpha-tubulin. Since this isotype is overexpressed in estramustine
      resistant human prostate carcinoma cells, these results indicate that beta III
      tubulin may play a role in the response to the effects of estramustine.

PMID- 9020787
TI  - Analysis of the interaction of water with the manganese cluster of photosystem II
      using isotopically labeled water.
AB  - The association of water with the Mn of the water oxidizing complex was
      investigated using H2(17)O- and 2H2O-reconstituted lyophilized photosystem II
      particles. The pulsed electron paramagnetic resonance (EPR) technique of electron
      spin echo envelope modulation (ESEEM) was used to investigate the interaction of
      the magnetic 2H and 17O nuclei with the paramagnetic S2 state of the Mn complex
      and other photosystem II components. ESEEM offers a much more specific and
      sensitive detection of this type of interaction than continuous wave (CW) EPR.
      Unlike earlier reports using CW EPR, these experiments did not detect any
      interaction of water with the multiline EPR signal from the S2 state of the Mn
      complex. No signals indicating specific interaction of either H or O with the
      multiline signal were detected. Signals due to 2H and 17O were detected only at
      the Larmour frequency, indicating nonspecific "distant ENDOR" effects. A weak
      interaction with 17O was detected both in S1, when the Mn is EPR silent, and in
      S2, but only on the high-field side of g = 2. This interaction may be with the
      Rieske iron-sulfur center in the cytochrome b6f complex. The results were the
      same whether the multiline signal was generated by 200 K illumination of dark
      frozen samples, or by room temperature illumination in the presence of the
      inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Illumination at room
      temperature in the presence of an electron acceptor to allow multiple turnovers
      of the system with cycling of the S states did not result in the appearance of
      any new interactions. These results appear to exclude close (less than 6 A)
      binding of water to the Mn center giving rise to the multiline signal, and also
      to exclude mechanisms in which water oxidation involves the breaking and re
      formation of the mu-oxo bridges of the Mn complex. They cannot, however, exclude
      models in which water binding to the manganese complex and direct oxidation by
      the manganese complex occur in the higher S states, or are catalyzed by one
      bis(mu-oxo) Mn dimer while oxidizing equivalents are accumulated in the S2 state
      by a second bis(mu-oxo) Mn dimer.

PMID- 9020788
TI  - The iron-sulfur clusters 2 and ubisemiquinone radicals of NADH:ubiquinone
      oxidoreductase are involved in energy coupling in submitochondrial particles.
AB  - The behavior of ubisemiquinone radicals and the iron-sulfur clusters 2 of
      NADH:ubiquinone oxidoreductase (Complex I) in coupled and uncoupled
      submitochondrial particles (SMP), oxidizing either NADH or succinate under steady
      state conditions, was studied. Multifrequency EPR spectra revealed that the two
      new g2 lines of the clusters 2, only observed during coupled electron transfer
      under conditions where energy dissipation is rate-limiting [De Jong, A. M. Ph.,
      Kotlyar, A. B., & Albracht, S. P. J. (1994) Biochim. Biophys. Acta 1186, 163
      171], are the result of a spin-spin interaction of 2.8 mT. Investigation of the
      radical signals present in coupled SMP indicated that more than 90% of the
      radicals can be ascribed to two types of semiquinones which are bound to Complex
      I (QI-radicals) or ubiquinol:cytochrome c oxidoreductase (Complex III; QIII
      radicals). The presence of QIII-radicals, but not that of QI-radicals, was
      completely abolished by uncoupler. Part of the QI-radicals weakly interact with
      the clusters 2 of Complex I. This uncoupler-sensitive interaction can amount to a
      splitting of the radical EPR signal of at most 1 mT, considerably weaker than the
      2.8 mT splitting of the g2 lines of the clusters 2. We propose that the 2.8 mT
      splitting of these g2 lines results from an energy-induced spin-spin interaction
      between the two clusters 2 within the TYKY subunit of Complex I. The two clusters
      2 show no interaction during electron transfer is uncoupled SMP or in fully
      reduced anaerobic-coupled SMP. The results point to a direct role of the Fe-S
      clusters 2 and the QI-radicals in the mechanism of coupled electron transfer
      catalyzed by Complex I.

PMID- 9020789
TI  - Uncompetitive substrate inhibition and noncompetitive inhibition by 5-n-undecyl-6
      hydroxy-4,7-dioxobenzothiazole (UHDBT) and 2-n-nonyl-4-hydroxyquinoline-N-oxide
      (NQNO) is observed for the cytochrome bo3 complex: implications for a Q(H2)-loop
      proton translocation mechanism.
AB  - The cytochrome bo3 ubiquinol oxidase complex from Escherichia coli contains two
      binding sites for ubiquinone(ol) (UQ(H2)). One of these binding sites, the
      ubiquinol oxidation site, is clearly in dynamic equilibrium with the UQ(H2) pool
      in the membrane. The second site has a high affinity for ubiquinone (UQ),
      stabilizes a semiquinone species, and is located physically close to the low-spin
      heme b component of the enzyme. The UQ molecule in this site has been proposed to
      remain strongly bound to the enzyme during enzyme turnover and to act as a
      cofactor facilitating the transfer of electrons from the substrate ubiquinol to
      heme b [Sato-Watanabe et al. (1994) J. Biol. Chem. 269, 28908-28912]. In this
      paper, the steady-state turnover of the enzyme is examined in the presence and
      absence of inhibitors (UHDBT and NQNO) that appear to be recognized as
      ubisemiquinone analogs. It is found that the kinetics are accounted for best by a
      noncompetitive inhibitor binding model. Furthermore, at high concentrations, the
      substrates ubiquinol-1 and ubiquinol-2 inhibit turnover in an uncompetitive
      fashion. Together, these observations strongly suggest that there must be at
      least two UQ(H2) binding sites that are in rapid equilibrium with the UQ(H2) pool
      under turnover conditions. Although these data do not rule out the possibility
      that a strongly bound UQ molecule functions to facilitate electron transfer to
      heme b, they are more consistent with the behavior expected if the two UQ(H2)
      binding sites were to function in a Q(H2)-loop mechanism (similar to that of the
      cytochrome bc1 complex) as originally proposed by Musser and co-workers [(1993)
      FEBS Lett. 327, 131-136]. In this model, ubiquinol is oxidized at one site and
      ubiquinone is reduced at the second site. While the structural similarities of
      the heme-copper ubiquinol and cytochrome c oxidase complexes suggest the
      possibility that these two families of enzymes translocate protons by similar
      mechanisms, the current observations indicate that the Q(H2)-loop proton
      translocation mechanism for the heme-copper ubiquinol oxidase complexes should be
      further investigated and experimentally tested.

PMID- 9020790
TI  - Reactions of isocytochrome c2 in the photosynthetic electron transfer chain of
      Rhodobacter sphaeroides.
AB  - Rhodobacter sphaeroides strains lacking cytochrome c2 (cyt c2), the normal
      electron donor to P870+ in light-oxidized reaction center (RC) complexes, are
      unable to grow photosynthetically. However, spd mutations that suppress the
      photosynthetic deficiency of cyt c2 mutants elevate levels of the cyt c2 isoform,
      isocyt c2. We monitored photosynthetic electron transfer in whole cells, in
      chromatophores, and with purified components to ascertain if and how isocyt c2
      reduced light-oxidized RC complexes. These studies revealed that several
      fundamental aspects of photosynthetic electron transfer were similar in strains
      that use isocyt c2 and wild-type cells. For example, P870+ reduction accompanied
      cytochrome c oxidation. In addition, photosynthetic electron transfer was blocked
      by the well-known cyt bc1 complex inhibitors antimycin and myxothiazol. However,
      even at the increased isocyt c2 levels present in these strains (approximately
      40% that of cyt c2 in wild-type cells), there was little, if any, of the rapid (<
      5 microns) electron transfer to P870+ that is characteristic of cytochromes bound
      to RC complexes at the time of the light flash. Thus, it appears that isocyt c2
      function limits the in vivo rate of P870+ reduction. Indeed, at low ionic
      strength in vitro, the apparent affinity of isocyt c2 for RC complexes (KD
      approximately 40 microM) is significantly lower than that of cyt c2 (KD
      approximately 1.0 microM). This reduced affinity does not appear to result from
      an altered mode of RC binding by isocyt c2 since electrostatic interactions make
      similar overall contributions to the binding of both cyt c2 and isocyt c2 to this
      membrane-bound redox partner. Thus, sequence, structural, or local conformational
      differences between cyt c2 and isocyt c2 significantly alter their apparent
      affinities for this physiologically relevant redox partner.

PMID- 9020791
TI  - Cholesterol modifies the properties of surface films of
      dipalmitoylphosphatidylcholine plus pulmonary surfactant-associated protein B or
      C spread or adsorbed at the air-water interface.
AB  - Cholesterol is a substantial component of pulmonary surfactant (approximately 8
      wt % or approximately 14 mol % of surfactant lipids). This study investigated the
      effect of cholesterol on the way in which hydrophobic SP-B and SP-C modulated the
      adsorption of lipid into the air-water interface and their respreading from
      collapsed phase produced on overcompression of the surface film. The properties
      of binary spread monolayers of SP-B or SP-C plus cholesterol (CH) were consistent
      with miscibility between the hydrophobic proteins and the sterol. Results from
      surface pressure versus area measurements at 23 degrees C on spread monolayers of
      dipalmitoylphosphatidylcholine (DPPC) plus SP-B in the presence of 8 wt %
      cholesterol implied that CH did not significantly affect the properties of the
      films of SP-B/(DPPC/CH) compared to those of binary SP-B/DPPC monolayers. In
      contrast, CH appeared to enhance the mixing of SP-C with DPPC/CH in ternary SP
      C/(DPPC/CH) films compared to the miscibility of SP-C with DPPC in the SP-C/DPPC
      films. It is estimated that about 10 wt % SP-C might remain in the SP-C/(DPPC/CH)
      monolayers compressed to high surface pressures of about 72 mN/m, whereas SP-C at
      concentrations of > or = 5 wt % was squeezed out at pi approximately 50 mN/m from
      SP-C/DPPC films without cholesterol. Cholesterol reduced the stability of the
      films of SP-B/(DPPC/CH) and SP-C/(DPPC/CH) when they had been compressed to pi
      approximately 72 mN/m, in contrast to films of SP-B/DPPC and SP-C/DPPC which
      exhibited a relatively slow relaxation from the collapse pressure of 72 mN/m.
      Dynamic cyclic compression beyond collapse of SP-B/(DPPC/CH) and SP-C/(DPPC/CH)
      monolayers showed that cholesterol diminished their postcollapse respreading
      compared to the respreading of the protein/DPPC films without cholesterol.
      Cholesterol, at 8 wt %, inhibited the rate of adsorption to the air-water
      interface at 35 degrees C of aqueous dispersions of DPPC containing 2.5 or 5 wt %
      SP-B or SP-C. The results suggest that cholesterol has an apparent negative
      influence on the surfactant surface properties, which are generally considered to
      be important in surfactant function, although increasing protein concentrations
      can counteract some of the negative influences.

PMID- 9020792
TI  - Ion binding induces closed conformation in Pseudomonas 7A glutaminase
      asparaginase (PGA): crystal structure of the PGA-SO4(2-)-NH4+ complex at 1.7 A
      resolution.
AB  - Pseudomonas 7A glutaminase-asparaginase (PGA) catalyzes the hydrolysis of D- and
      L-isomers of glutamine and asparagine. X-ray quality type-1 crystals of PGA have
      been obtained from 2.0 M ammonium sulfate. The space group is C222(1) with unit
      cell dimensions a = 78.62, b = 135.80, and c = 137.88 A. The tetrameric molecule
      is located on a crystallographic 2-fold axis, and two subunits form the
      asymmetric portion of the unit cell. The structure was solved by the molecular
      replacement method and refined at 1.7 A resolution to an R = 19.9% with a good
      geometry of the model, G = 0.05. The resultant electron density maps enabled us
      to resolve individual constituent atoms of most residues and introduce minor
      revisions to the amino acid sequence. The catalytic loop, Thr20-Gly40, is in the
      closed conformation with excellent electron density in both subunits. A sulfate
      ion and an ammonium ion are bound in the substrate binding site and interect with
      the loop. This interaction appears to be responsible for the observed closed
      conformation. New arguments supporting Thr20 as the catalytic nucleophile in the
      asparaginase activity are proposed.

PMID- 9020793
TI  - Equilibrium and kinetic analyses of unfolding and refolding for the conserved
      proline mutants of tryptophan synthase alpha subunit.
AB  - To elucidate the role of conserved proline residues of the tryptophan synthase
      alpha subunit from Escherichia coli in stability and folding, equilibrium and
      kinetic studies of the unfolding-refolding induced by guanidine hydrochloride for
      six mutant alpha subunits (Pro-->Ala) were carried out by peptidyl circular
      dichroism and aromatic fluorescence measurements at pH 7 and 25 degrees C. These
      results were analyzed assuming the presence of one intermediate (I) state in the
      denaturation process. (I) For all mutant and wild-type proteins, the Gibbs energy
      change (delta Gni(H2O)) in water between the native (N) and I states coincided
      with the difference (delta G++u(H2O)-delta G++r(H2O)) between the activation
      Gibbs energy changes in water for the unfolding (delta G++u(H2O) and refolding
      (delta G++r(H2O) reactions. This means that the early folding intermediate of the
      alpha subunit corresponds to the equilibrium intermediate. Delta Gni(H2O) values
      of all mutant proteins decreased compared with that of the wild-type protein.
      Gibbs energy change (delta Gid(H2O) in water between I and the denatured (D)
      states was not substantially affected by the substitutions. Delta G++u(H2O) and
      delta G++r(H2O) decreased and increased, respectively, for all mutant proteins.
      (2) Six conserved prolines played roles in stability and folding of the alpha
      subunit in a different manner: prolines 28 and 96 by stabilizing the N state and
      prolines 28, 96, 132, and 207 by destabilizing the I state. The contributions of
      prolines 57 and 62 to the stability were marginal. (3) Cis proline 28 was not the
      origin of the slow phase in the refolding kinetics assumed to arise from the cis
      trans isomerization reaction of proline.

PMID- 9020794
TI  - Site-directed mutagenesis of the sodium pump: analysis of mutations to amino
      acids in the proposed nucleotide binding site by stable oxygen isotope exchange.
AB  - A model for the active site of P type ATPases has been tested by site-directed
      mutagenesis of amino acids in two conserved sequences of Mg(2+)-dependent and
      Na(+)- and K(+)-stimulated ATPase. The mutants K501R, K501E, D586E, D586N, P587A,
      and P588A were expressed in yeast cells and compared with wild type. In addition
      to previously published assays of adenosine 5'-triphosphate binding and
      hydrolysis, measurements of 18O exchange between Pi and water have been used to
      identify steps in the E2 half of the reaction cycle affected by the mutations.
      The study supports the prediction that K501 in the KGAP sequence interacts with
      adenosine 5'-triphosphate. However, quantitative comparisons of the effect of
      mutation K501E on the activity with the effects of mutations to an enzyme of
      known structure that also catalyzes phosphoryl group transfer make a direct role
      for the positive charge on the side chain of K501 in catalysis by stabilizing the
      transition state unlikely. No evidence for the predicted interaction between D586
      and the hydroxyl groups of ribose was found. However, the data do indicate that
      the spatial organization of the loop containing the DPPR sequence is critical for
      phosphorylation of the enzyme. A role for D586 in coordinating the Mg2+ that is
      required for activity is proposed.

PMID- 9020796
TI  - Apolipoprotein B gene regulatory factor-2 (BRF-2) is structurally and
      immunologically highly related to hepatitis B virus X associated protein-1 (XAP
      1).
AB  - Hepatic cell-specific expression of the human apolipoprotein B (apoB) gene is
      controlled by at least four cis-acting elements located between positions -128
      and +122 [Chuang, S. S., & Das, H. K. (1996) Biochem. Biophys. Res. Commun. 220,
      553-562]. The distal element (-128 to -85) appears to be liver specific because
      it shows positive activity in HepG2 cells and negative activity in HeLa cells.
      ApoB gene regulatory factor-2 (BRF-2) interacts with the sequence (-104 to -85).
      BRF-2 has been purified from rat liver nuclear extract, and its molecular weight
      has been determined to be approximately 120 kDa [Zhuang et al. (1992) Mol. Cell.
      Biol. 12, 3183-3191]. In this paper we report the isolation of two isoforms of
      BRF-2 by further purification using high-performance liquid chromatography. Both
      isoforms produced a single approximately 120-kDa band in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis detected by silver stain. The amino acid
      sequences of two tryptic peptides derived from HPLC-purified heavier BRF-2
      isoform were determined to be YLAIAPPIIK and ALYYLQIHPQELR. These two peptides
      were found to share 100% sequence homology with human hepatitis B virus X
      associated protein-1 (XAP-1) and monkey UV-damaged DNA-binding protein (UV-DDB).
      Anti-peptide antisera raised against two synthetic peptides of XAP-1 recognized a
      approximately 120-kDa polypeptide band in both BRF-2 isoforms in a western blot
      analysis. By using apoB promoter fragments containing various internal deletions
      and a substitution mutation as templates for gel mobility shift assays, we
      identified the region between -104 and -85 as crucial for binding by the high
      molecular weight form. In contrast, the lower molecular weight isoform bound to
      all apoB mutants tested. Anti-peptide 2 antiserum directed against XAP-1 was
      found to inhibit in vitro transcription of the apoB gene in rat liver nuclear
      extracts by 50%. These results suggest that BRF-2 and XAP-1 are structurally and
      immunologically highly related trans-activators of the apoB gene. We propose that
      BRF-2 exists both as a monomer (BRF-2M) and as a homooligomer. probably a
      homodimer (BRF-2D), in solution; oligomerization appears to be an essential step
      for imparting sequence-specificity to BRF-2 protein and thereby facilitating its
      role as a trans-activator of the apoB gene.

PMID- 9020795
TI  - Synthetic peptides from mouse Fc receptor (MoFc gamma RII) that alter the binding
      of IgG to MoFc gamma RII.
AB  - Fc receptors are transmembrane proteins, found on the surfaces of immune cells,
      that aid in the removal of foreign pathogens by binding to antibody-coated
      targets via the Fc regions of the antibodies. Using peptides synthesized on pins,
      overlapping dodecapeptides (170) were synthesized to cover the extracellular
      region of the mouse Fc receptor for IgG, moFc gamma RII. The peptides were
      screened for antibody binding activity by using multivalent immune complexes
      composed of anti-dinitrophenyl monoclonal mouse IgG1 (ANO6) and dinitrophenyl
      conjugated to human serum albumin (DNP-HSA). Assays were also carried out with an
      anti-moFc gamma RII monoclonal rat IgG (2.4G2). The peptides that interacted with
      these antibodies prompted the synthesis of two soluble peptides: peptide A [Fc
      gamma RII-(108-119), RCHSWRNKLLNRamide] and peptide B [Fc gamma RII-(153-165),
      CKGSLGRTLHQSKamide]. Monomeric S-alkylated (A, B), homodimeric (AA, BB),
      heterodimeric (AB), and scrambled homodimeric (CC, DD) forms of these peptides
      were synthesized and examined for their ability to inhibit immune-complex binding
      to immobilized soluble Fc gamma RII. Peptides AA and CC completely inhibited
      immune-complex binding while each of the other peptides partially inhibited
      binding (AB, 80%; A, 80%; BB, 65%; DD, 64%; B, 52%). The pair of monomeric moFc
      gamma RII peptides and the set of five dimeric peptides showed the same increase
      in binding inhibition with increasing net positive charge per residue. These
      results suggest that the Fc region of IgG binds to the solvent-exposed B/C and
      F/G loops of the moFc gamma RII receptor through predominantly electrostatic
      forces.

PMID- 9020797
TI  - Fluorescent probes attached to Cys 35 or Cys 84 in cardiac troponin C are
      differentially sensitive to Ca(2+)-dependent events in vitro and in situ.
AB  - The goal of the current study was to generate recombinant cTnC proteins with
      single Cys residues as sites for attachment of fluorescent probes that can
      distinguish between the structural effects of myosin cross bridges and direct
      Ca2+ binding to cTnC (cardiac and slow skeletal troponin C) in skinned fibers. We
      anticipated that cTnC proteins which retain the endogenous Cys 35 (cTnC(C35)) or
      Cys 84 (cTnC(C84)) would provide fluorescent probes with distinct
      microenvironments, since these residues are on opposite sides of the globular
      regulatory domain. In vitro experiments that showed IAANS (2-(4'
      (iodoacetamido)anilino)naphthalene-6-sulfonic acid) coupled to Cys 35 can induce
      unwanted structural perturbations as evidenced by a decreased affinity of site II
      for Ca2+ when IAANS-labeled cTnC(C35) is bound to cTnI. Important structural
      features involving Cys 35 in the inactive site I are suggested by a Ca(2+)
      dependent increase in reactivity of Cys 35 with sulfhydryl specific reagents when
      cTnC(C35) is associated with cTnI. These characteristics are not seen for
      cTnC(C84). When incorporated in situ into skinned cardiac muscle fibers, native
      cTnC with IAANS bound to both Cys 35 and Cys 84 showed a pCa50 of fluorescence
      which preceded that of force, while the pCa50 values of both force and
      fluorescence were coincident for IAANS-labeled cTnC(C84). Disruption of force
      producing myosin cross bridges had no effect on the pCa50 of fluorescence for
      IAANS-labeled cTnC(C84), but induced a rightward shift in the pCa50 of
      fluorescence for IAANS-labeled native cTnC. These data can be interpreted to
      indicate that cTnC with IAANS bound to both Cys 35 and C84 senses either myosin
      cross bridges or direct Ca2+ binding and myosin-induced cooperativity, while
      IAANS bound to Cys 84 alone senses conformations that are tightly coupled with
      force generation.

PMID- 9020798
TI  - The evolution of complexity in human brain development: an EEG study.
AB  - Analysis of the EEG as a signal from a deterministic non-linear system should, in
      principle, allow insights into the complexity of underlying brain activity. We
      examined the capability of this method to analyse the marked changes in brain
      activity during normal brain development. Resting EEGs of 54 healthy children
      (newborns to 14 years old) and of 12 normal adults were recorded digitally. The
      following parameters were calculated: correlation dimension, a measure of the
      complexity of the underlying system, and the first Lyapunov coefficient,
      indicating the system's 'unpredictability'. Analysis of variance (ANOVA) was
      performed with probands grouped by age. The subgroups of children older than 1
      year was further examined by regression analysis. In all analysed epochs,
      Lyapunov coefficients were significantly positive (P < 0.0001. t-test). The
      presence of non-linear dynamics was asserted statistically in 64-76% of examined
      epochs. A highly significant increase in correlation dimension with age was found
      in all examined leads (P < 0.0001, ANOVA). In all age groups, marked differences
      in correlation dimension in different brain regions became evident (P < 0.01
      0.0001, ANOVA). Evidence for the presence of non-linearity can be found even in
      newborns. Brain maturation was reflected in a marked and highly significant
      increase in correlation dimension (complexity). Our work indicates that non
      linear dynamics analysis is suitable for measuring complexity of brain activity
      during maturation and provides age-dependent normal values as a basis for further
      study.

PMID- 9020799
TI  - The significance of ictal depth EEG patterns in patients with temporal lobe
      epilepsy.
AB  - We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal
      lobe complex partial seizures. All patients had a minimum of 1 year follow-up
      following temporal lobectomy. We classified seizure onset pattern as rhythmic
      activity, attenuation, or repetitive spikes or spike wave complexes. The most
      common pattern of seizure onset was rhythmic activity and the next most common
      pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure
      onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns.
      The degree of hippocampal gliosis strongly predicted the type of seizure onset
      pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was
      associated with mild gliosis, and the repetitive spike pattern was associated
      with severe gliosis. We classified seizure onset as focal or regional based on
      the number of electrode contacts that were involved by the ictal EEG. A focal
      seizure onset was associated with an excellent outcome following temporal
      lobectomy.

PMID- 9020800
TI  - On-line EEG classification during externally-paced hand movements using a neural
      network-based classifier.
AB  - EEGs of 6 normal subjects were recorded during sequences of periodic left or
      right hand movement. Left or right was indicated by a visual cue. The question
      posed was: 'Is it possible to move a cursor on a monitor to the right or left
      side using the EEG signals for cursor control?' For this purpose the EEG during
      performance of hand movement was analyzed and classified on-line. A neural
      network in form of a learning vector quantizertion (LVQ) with an input dimension
      of 16 was trained to classify EEG patterns from two electrodes and two time
      windows. After two training sessions on 2 different days, 4 subjects showed a
      classification accuracy of 89-100%. For two subjects classification was not
      possible. These results show that in general movement specific EEG-patterns can
      be found, classified in real time and used to move a cursor on a monitor to the
      left or right. On-line EEG classification is necessary when the EEG is used as
      input signal to a brain computer interface (BCI). Such a BCI can be a help for
      handicapped people.

PMID- 9020801
TI  - Extensible biosignal (EBS) file format: simple method for EEG data exchange.
AB  - Increasing use of computer technology in EEG research requires the creation of
      standardized data formats to transmit, exchange, analyze or modify mainly EEG/MEG
      as well as mere general polygraphic data. The extensible biosignal file format
      (EBS) has been designed for easy use. The concept of the EBS format is a simple
      structure of variable size, consisting of one fixed and two variable headers and
      a data section. In the variable header, any information can be stored in
      attributes. The data are archived in one of 3 organizational forms: channel
      order, temporal order, or compressed. The format supports various data types,
      multiple biosignals (ECG, EEG, MEG, polygraph), annotations, processing history,
      location diagrams (CGM), 16 hit ISO 10646 character set, random access to large
      amounts of data, global or private extensions, self-identification, and multiple
      tools for conversion, modification and visualization which are freely available
      in source code.

PMID- 9020802
TI  - Technical implementation and clinical findings/results of monitoring oxygen
      saturation in patients referred for long-term EEG monitoring.
AB  - Recent technical developments allow the recording of a patient's oxygen
      saturation (SpO2) simultaneously with intensive long-term EEG monitoring (LTM).
      Clinically significant information from this enhanced multi-system physiological
      monitoring device can contribute to more accurate diagnoses in patients referred
      for LTM. This report covers the technical usage of combined SpO2/EEG recordings
      in a small group of patients. Clinically, the findings on the SpO2 monitor helped
      to define the diagnosis in many of these patients. In a few, the SpO2 changes
      were diagnostic in their own right and prompted referral to our Sleep Disorders
      Laboratory. From a research aspect, the details of the morphology and timing of
      the oxygen desaturations and EEG show several interesting relationships with
      respect to the dynamics of seizure semiology and respiratory physiology.

PMID- 9020803
TI  - Periodic electroencephalographic pattern in subacute sclerosing panencephalitis
      modified by preexisting damaged cerebral hemisphere.
AB  - We report a 15 year old girl with a childhood hemiplegia, who developed a recent
      progressive intellectual decline associated with elevated globulins and measles
      antibody titres in the cerebrospinal fluid, indicating a diagnosis of subacute
      sclerosing panencephalitis (SSPE). The magnetic resonance imaging revealed left
      hemispheric atrophy concordant with a long-standing right hemiplegia, and
      electroencephalography exhibited lateralized periodic complexes (PCs) over the
      right hemisphere concordant with left-sided myoclonic jerks. The modification of
      PCs in our patient due to preexisting damaged cerebral hemisphere illustrate that
      a fairly functional cortex and subcortical white matter are needed for the
      expression of the PCs of SSPE.

PMID- 9020804
TI  - On-line brain potential correlates of right parietal patients' attentional
      deficit.
AB  - EEG potentials evoked by cues and targets were recorded in Posner's visual cueing
      task from 10 patients with lesions of the right parietal cortex and from age
      matched healthy subjects. The patients' N1 component evoked by left-side cues was
      reduced at the right-parietal recording site, suggesting a general impairment in
      processing left-side visual input. As usual, patients' keypress responses were
      delayed when left targets were preceded by right cues. There were two correlates
      of this delay in the patients' EEG potentials evoked by the critical combination
      of right cue/left target: their mean amplitude 160-280 ms after target onset
      ('Nd') was less negative than with other combinations of cue and target, and the
      following frontal P300 was enhanced. The Nd reduction seems to be an on-line
      measure of patients' momentary decrease of attention for the left hemifield,
      while the frontal P300 might reflect the patients' attempts at reorienting. In
      conclusion, different components were sensitive to different aspects of the
      patients' disorder, suggesting the utility of this approach for developing
      detailed hypotheses on the mechanisms of attentional deficits involved in visual
      extinction and neglect.

PMID- 9020806
TI  - Increase of posterior cerebral artery blood flow velocity during threshold
      repetitive magnetic stimulation of the human visual cortex: hints for neuronal
      activation without cortical phosphenes.
AB  - To analyze the effects of low intensity repetitive transcranial magnetic
      stimulation over the occipital cortex on regional cerebral perfusion, bilateral
      simultaneous monitoring of posterior cerebral artery blood flow velocity was
      performed using transcranial Doppler ultrasonography in 14 healthy subjects.
      During 20 s of unilateral magnetic stimulation with 3 Hz and 6 Hz a significant
      increase of ipsilateral flow velocity was observed during both stimulus
      conditions (3 Hz, 10.2 +/- 3.7%; 6 Hz, 12.8 +/- 4.7%). A significantly smaller
      flow velocity increase occurred also in the contralateral posterior cerebral
      artery (3 Hz, 8.6 +/- 4.0%; 6 Hz, 10.6 +/- 4.1%). Flow velocity increases were
      similar to values reported in the literature for physiological activation
      paradigms so that excessive excitation of the visual cortex does not seem to
      occur during repetitive magnetic stimulation. The largest increase of flow
      velocity was observed in the ipsilateral posterior cerebral artery of 5 subjects
      who experienced phosphenes in the contralateral visual half-field during
      stimulation (14.3 +/- 4.1%: mean of 3 and 6 Hz stimulation). In the other 9
      subjects significant velocity increases indicated cortex activation in the
      absence of cortical phosphenes. The occurrence of maximum velocity responses
      within 2-3 heart beats following the first cortex stimulus points to a fast
      adjustment of cerebral perfusion in response to transcranial brain stimulation.

PMID- 9020805
TI  - Multichannel auditory event-related brain potentials: effects of normal aging on
      the scalp distribution of N1, P2, N2 and P300 latencies and amplitudes.
AB  - Event-related potentials (ERPs) were recorded at 17 leads in an auditory oddball
      paradigm in 172 normal healthy subjects aged between 20 and 88 years. With
      advancing age, N1 latency increased parietally (0.12 ms/year), P2 latency
      increased frontally (0.34 ms/ year) and N2 and P300 latencies increased all over
      the scalp (0.37 ms/year for N2; 0.92 ms/year for P300). P300 latency/age
      relationship was curvilinear with accelerated latency increase in elderlies (0.35
      ms/year for subjects below 60 years; versus 2.03 ms/year for subjects above 60
      years). With advancing age, standard tone ERP amplitudes were enhanced frontally
      (0.03 microV/year for N1; 0.07 microV/year for P2), N2 amplitudes were attenuated
      frontally (0.11 microV/year) and P300 amplitudes were attenuated parietally (0.15
      microV/year). Multichannel analysis demonstrated that ERP latencies and
      amplitudes depended on electrode location. Standard tone ERP latencies changed
      their topographic distribution with age, whereas target tone ERP latencies did
      not. While N1 amplitude distribution was unaffected by age, P2, N2 and P300
      topography changed significantly with age: P2 topography to a more frontal
      distribution and increased 'global field power'; N2 topography to a more parietal
      distribution: P300 topography to a more frontal and more equipotential
      distribution Thus, specific age effects on different ERP components were
      confirmed.

PMID- 9020807
TI  - Human long-latency responses to brief interaural disparities of intensity.
AB  - The electroencephalographic responses to abrupt changes in interaural differences
      of time (ITD) and intensity (IID) should provide important information on the
      dynamic characteristics and integrity of the binaural mechanisms detecting the
      azimuthal shifts of a sound image. However, a change in either or both of these
      cues to sound lateralization would stimulate not only the binaural mechanisms but
      also the monaural ones. There are several reports evidencing that in the case of
      ITD changes this problem can be overcome by using time-shifted noise or
      repetitive clicks. Any change in IID, however, will inevitably have a stimulating
      effect also on purely monaural mechanisms. Therefore, the stimulation techniques
      described in the literature so far for recording the long-latency responses
      related to IID mechanism cannot be regarded as being specific for binaural
      mechanisms. We used dichotically presented 100/s click trains which were
      amplitude modulated with a random sequence of 50 or 100 ms square wave-intervals,
      so that the sound intensities at the two ears simultaneously alternated between
      60 dB and 80 dB levels except during brief periods of time (50 ms) in which the
      interaural intensity balance was impaired, leading to an IID of 20 dB every 2 s.
      Owing to the fact that the cortical mechanisms remain unresponsive to repetitive
      stimuli presented with intervals shorter than a certain recovery period, this
      stimulus did not evoke any significant potential when it was presented
      monotically or diotically, yet it could produce lateral sound image shifts and
      therefore evoke pronounced long-latency responses when presented dichotically.
      The main components N1 and P2 of these shift responses and those of the pip
      responses, also recorded from the same subjects, were compared with respect to
      their midline distributions and hemispheric or bilateral asymmetries. The
      significant differences found between the shift and pip responses indicated that
      those evoked by the IID stimulation we designed should not be considered simply
      as a non-specific vertex potential.

PMID- 9020808
TI  - Expectancy and response strategy in a three-choice visual task.
AB  - We investigated the relationship between sensorial discrimination and motor
      response by means of movement-related potentials, in a task where subjects had to
      discriminate between 3 stimuli presented visually in a random way. The results
      indicate that subjects anticipate the response to each type of stimulus by
      following a probabilistic criterion in the absence of a warning stimulus. This
      criterion entails an erroneous lateralization of cerebral activation and a
      significant increase in reaction time, despite the reduction of errors.

PMID- 9020809
TI  - Long-term practice effects on a new skilled motor learning: an
      electrophysiological study.
AB  - Cortical functions concerned with the execution of skilled movements can be
      studied through complex interactive tasks. Skilled performance task (SPT) offers
      the greatest deal of information about the electrophysiological components
      reflecting pre-programming, execution of the movement and control of the results.
      Overall, these components are indicated as "movement-related brain
      macropotentials' (MRBMs). Among them, Bereitschaftspotential (BP) reflects
      cerebral processes related to the preparation of movement and skilled performance
      positivity (SPP) reflects control processes on the result of performance. There
      is some evidence supporting a training effect on MRBMs, but less clear is whether
      long-term practice of a skilled activity could modify learning strategies of a
      new skilled task. We recorded MRBMs in subjects trained for a long time to
      perform a highly skillful athletic activity, i.e. gun shooting, and in a group of
      control subjects without any former experience in skilled motor activities. Our
      findings demonstrated the existence of a relationship between pre-programming and
      performance control, as suggested by decrease of BP amplitude and increase of SPP
      amplitude in presence of high levels of performance. Long-term practice seems to
      develop better control models on performance, that reduce the need of a high
      mental effort in pre-programming a skilled action.

PMID- 9020810
TI  - The differential effects of extremity and movement side on the scalp distribution
      of the readiness potential (RP) and the stimulus-preceding negativity (SPN).
AB  - In a time estimation task subjects had to press a button 3 s after the
      presentation of a warning stimulus. Two seconds after the movement they were
      informed about their performance by a knowledge of results (KR) stimulus.
      Preceding the movement a readiness potential (RP) and prior to the presentation
      of the KR stimulus a stimulus-preceding negativity (SPN) was recorded. Movement
      side (left/right) and extremity (hand/foot) were varied within subjects to
      demonstrate that the RP but not the SPN is affected by such manipulations. The
      scalp distribution of the late part of the RP was affected by movement side and
      extremity. Yet it exhibited the expected lateral asymmetry only preceding a
      movement of the left hand or of the right foot. The scalp distribution of the SPN
      was not affected by extremity. The size of the right hemisphere preponderance of
      the SPN depended on movement side following a finger flexion, but not following a
      plantar flexion of the foot. The experimental design was intended to avoid the
      temporal overlap between movement-related and stimulus-related activity. Yet it
      is argued that both results of this experiment can best be explained by such an
      overlap.

PMID- 9020811
TI  - Brain potentials with old/new distinction of non-words and geometric figures.
AB  - Event-related potentials (ERPs) were recorded in a continuous memory recognition
      task. Readable non-words and abstract geometric figures were presented in an
      alternating manner with an inter-stimulus interval of 2.1 s. Probability of item
      repetition was 0.25, a lag of one item lay between initial presentation and
      repetition. OLD/NEW distinction was indicated by the subject's motor response.
      Using linked-mastoid electrodes for reference, material-specific hemispheric
      asymmetries of ERPs started 150 ms after stimulus onset in temporo-lateral and
      parietal recordings with ERPs elicited by non-words being lateralized to the left
      and those by figures to the right. Clear OLD/NEW ERP effects were found with non
      words: Starting about 200-250 ms after stimulus presentation, ERPs of formerly
      presented (OLD) items were more positive-going in recordings over the midline
      than ERPs of items that were new and to be repeated (NEW). In contrast, no local
      OLD/NEW ERP-difference was found with figures. In some brain regions, OLD/NEW ERP
      differences were larger over the left hemisphere compared to the right. This
      finding, however, did not differ between non-words and figures.

PMID- 9020812
TI  - Developmental changes in the alpha response system.
AB  - Evoked and event-related brain potentials (ERPs) may be regarded as originating
      from the reorganization of the spontaneous EEG rhythms. The main objective of the
      present research was to study the alpha responses in 6-11 year old children to
      determine whether the ability to reorganize alpha activity after external
      stimulation demonstrates developmental changes that could reflect variations in
      information processing with increased age. A total of 50 children aged 6-11
      years, divided into 5 age groups, and 10 young adults were assessed in a passive
      and an oddball condition. Alpha responses in the passive and non-target ERPs at
      Fz, Cz and Pz were analyzed to assess quantitatively the repeatability (phase
      locking) of the evoked alpha oscillations. The alpha responses in 6-11 year old
      children were different from those in adults: (1) adults had significantly lower
      amplitude and stronger phase-locking than children; (2) adults had maximal alpha
      amplitudes and phase-locking over the vertex, whereas children displayed maximal
      responses over the parietal site; (3) the phase-locking of eldest (10-11 year
      old) children was as strong as in adults. These findings indicate that the alpha
      response system is functionally involved in 6-11 year old children, though its
      development is not complete at the age of 11, and the magnitude and the phase
      locking parameters may relate to different functional aspects of the alpha
      response system. Thus, younger children do produce alpha responses during
      information processing, but are not able to engage this system as strongly as
      older children and adults.

PMID- 9020813
TI  - Chaotic behavior of EEG slow-wave activity during sleep.
AB  - The study of the dynamics of non-linear systems allows the evaluation of the
      correlation dimension which, in turn, provides an estimate of the number of
      variables needed to model the process. In such a view, the correlation dimension
      was calculated for the profiles of the EEG slow-wave activity during sleep
      obtained from 7 young normal controls and in their corresponding artificial
      stochastic signals. It was possible to evaluate the complexity of all the real
      profiles which exhibited an average dimension of 3.76 (SD 0.331), but not that of
      the artificial control ones. This allows us to conclude that sleep regulation
      might be considered as a deterministic non-linear process and that the already
      proposed two-process model of sleep regulation needs to include additional
      variables with non-linear interactions.

PMID- 9020814
TI  - Distributions and sources of magnetoencephalographic K-complexes.
AB  - Whole-head magnetoencephalographic (MEG) and midline electroencephalographic
      (EEG) signals were simultaneously recorded from 6 subjects during drowsiness and
      sleep to define the topography and source distribution of K-complexes. In light
      sleep, K-complexes were also triggered by infrequent tones. Distributions of
      spontaneous and triggered magnetic K-complexes did not differ systematically, nor
      did those evoked by right- and left-ear stimuli, but there were large intra- and
      interindividual differences. Minimum-norm estimates and current dipoles were used
      to characterize the source currents. Current direction and distribution varied
      remarkably between the K-complexes appearing in similar situations. In one
      subject, most K-complexes were adequately modelled with two current dipoles which
      were situated in the left and right inferior parietal lobes. In other subjects,
      the current distributions were more complex, suggesting several brain regions to
      be active during one K-complex; the dominant foci were in frontal and parietal
      lobes. Our results suggest that the K-complex is not a stereotyped response of
      the cortex to internal or external stimuli, comparable to evoked responses, but a
      diffuse and variable cortical reaction during which large areas of cortex may be
      active.

PMID- 9020815
TI  - Rapid eye movements density as a measure of sleep need: REM density decreases
      linearly with the reduction of prior sleep duration.
AB  - In the recovery nights from total and partial sleep deprivation there is a
      reduction of oculomotor activity during paradoxical sleep as compared to baseline
      nights. Aims of the present within-subjects study are to contribute in
      understanding the nature of the relationship between REM density and sleep need
      and to evaluate whether an inverse relationship exists between REM density and
      slow wave sleep (SWS) amount. Six healthy subjects were studied for 7 consecutive
      weeks with standard polysomnographic recordings. Variations in REM density were
      assessed in the recovery nights following a gradual sleep restriction, obtained
      by postponing the sleep onset time while maintaining the final awakening time
      constant. Results indicate that sleep curtailment decreases REM density in the
      ensuing recovery nights; the decrease is linearly related to the amount of sleep
      curtailment. The decrease in REM density parallels an increase in SWS, while no
      corresponding variation was found neither in the duration of paradoxical sleep
      nor in the latency of any other sleep stage. These results suggest that REM
      density could be used as a measure of sleep need.

PMID- 9020816
TI  - Ordinary least squares dipole localization is influenced by the reference.
AB  - It is shown empirically, analytically and in simulations that common and average
      referenced recordings differentially affect the accuracy of equivalent source
      estimates. This effect is mediated by the influence of the reference on noise
      correlations. The general conclusion of this analysis is that, if software only
      allows for ordinary least squares estimation (OLS), then average referencing
      should be preferred, although these estimates will still be sub-optimal. Optimal
      estimates are derived by generalized least squares (GLS) which accounts for
      correlated noise. With GLS, average and common referenced recordings give rise to
      comparable accuracy.

PMID- 9020817
TI  - MEG-compatible multichannel EEG electrode array.
AB  - We describe an EEG electrode array, which is designed to facilitate simultaneous
      multichannel EEG and MEG recordings. The special electrode design allows shorter
      preparation times and more reliable contacts than commercially available
      solutions. The electrode array is magnetically compatible with MEG and the low
      profile electrodes consume minimal space inside the magnetometer.

PMID- 9020819
TI  - The effect of current direction induced by transcranial magnetic stimulation on
      the corticospinal excitability in human brain.
AB  - Evoked spinal cord potentials (ESCPs) from the cervical epidural space and motor
      evoked potentials (MEPs) from the hand muscles were recorded simultaneously in 6
      subjects following transcranial magnetic stimulation in two different coil
      orientations on motor cortex. The onset latency of the MEPs was approximately 1
      ms shorter when the induced current flowed in a latero-medial direction (L-M
      stimulation) on the motor cortex as compared to a postero-anterior direction (P-A
      stimulation). Hence, L-M stimulation elicited an earlier component of the ESCPs
      than that induced by P-A stimulation. During general anesthesia with Sevoflurane,
      only the first component of the ESCPs could be elicited routinely following L-M
      stimulation. In contrast, all components of the ESCPs were dramatically
      attenuated following P-A stimulation. Moreover, first component latency of the
      ESCPs induced by L-M stimulation was almost the same as that induced by
      transcranial anodal electrical stimulation. These results suggest that if the
      induced current following transcranial magnetic stimulation flows in a latero
      medial direction on motor cortex, it preferentially stimulates the corticospinal
      tract non-synaptically (producing a D-wave). However, if the induced current
      flows in a postero-anterior direction, it preferentially stimulates the
      corticospinal tract trans-synaptically (producing I-waves). Therefore, the
      direction of magnetically induced current is crucial in determining corticospinal
      excitability in the human brain.

PMID- 9020818
TI  - Supplementary motor area in spatial coordination of bilateral movements: a new
      aspect to 'the SMA debate'?
AB  - To test whether the supplementary motor area's (SMA) role is confined to
      determining the 'temporal' but not the 'spatial' properties of a movement (H.H.
      Kornhuber et al., in: W.A. Hershberger (Ed.), Volitional Action, Elsevier,
      Amsterdam, 1989, pp. 107-168), movement-related scalp-recorded negative DC
      potential shifts were recorded in bilateral movements requiring complex spatial
      coordination. In such bilateral continuous rotation movements, the effect of the
      rotation sense (symmetrical vs. antisymmetrical), i.e. the direction in which an
      arm or a finger rotated in relation to the other, heavily affected DC shifts over
      the frontocentral midline. Antisymmetrical rotation of upper limb segments was
      associated with higher negative DC shifts than symmetrical rotation was. This was
      true for rotations in the sagittal plane, irrespective of whether the rotation
      involved predominantly proximal muscles (by a rotation predominantly in the
      shoulder) or only distal muscles (by a rotation in the metacarpo-phalangeal joint
      of the index finger). If these negative cortical DC-shifts over the frontocentral
      midline relate to activity of mesial frontocentral structures including the SMA,
      then the present results suggest that there is a role for these cerebral areas in
      spatial coordination of bilateral movements. Surprisingly, this was not the case
      for similar finger movements performed in the frontal plane. The results of the
      present study and particularly the considering of some fundamentals of
      theoretical physics and of Popper's philosophy of science, made us revise our
      assumption motivating the present study, that time and space would represent two
      orthogonal factors of a movement and that the contributions of a particular
      cerebral motor area (such as the SMA) to 'spatial parameters' versus 'temporal
      parameters' of a movement can thus be teased apart.

PMID- 9020820
TI  - Electrophysiological findings in patients who received radiation therapy over the
      brachial plexus: a magnetic stimulation study.
AB  - Clinical and electrophysiological findings of 47 asymptomatic females who
      received radiation therapy (RT) over their brachial plexus region are presented
      and compared with 8 radiation-induced brachial plexopathy (RBP) and 4 neoplastic
      brachial plexopathy (NBP) patients. In the asymptomatic group, abnormal findings
      were more frequent in patients whose post-RT period was longer than 1 year.
      Flexor carpi radialis H reflex was delayed or absent in 19 patients (52%) in this
      subgroup of asymptomatic cases, as compared to only 2 (18%) of the patients with
      post-RT periods of less than 1 year. Magnetic cervical nerve root stimulation was
      performed in 16 asymptomatic cases, with the conclusion that there was no
      significant difference between the irradiated and non-irradiated sides with
      regard to latencies, amplitudes and areas of the muscle responses. In spite of
      this, muscle response amplitudes and areas on both sides were significantly lower
      than those obtained from healthy controls. It was postulated that this finding
      resulted from hypoexcitability to magnetic stimulation produced by slight nerve
      root damage. Any part of the brachial plexus could be affected in RBP and NBP
      patients. Myokymic discharges were found at a high rate (87.5%) in RBP group.
      Cervical magnetic nerve root stimulation may have a diagnostic value in these
      patients in localizing the nerve lesion over the brachial plexus.

PMID- 9020821
TI  - Electromyographic and positional changes in the elbows of spastic hemiparetic
      patients during walking.
AB  - The displacement of the paretic elbow of hemiparetic patients into flexion during
      walking is an acknowledged associated reaction characteristic of upper limb
      spasticity. The main purpose of this study was to examine the step-dependent
      pattern and magnitude of the angular and electromyographic changes which take
      place during this flexion movement. Steps-related changes in elbow angle were
      measured on the paretic side of 14 hemiparetic patients during walking with a 4
      point cane. The EMG activity of the ipsilateral biceps and triceps brachii
      muscles was concomitantly recorded. The activity of the brachioradialis muscle in
      8 patients was monitored as well. In another trial, the angular and
      electromyographic activities were measured bilaterally in 7 patients during free
      walking. Flexion movement on the paretic side was characterized by a steep
      increase in flexion occurring during the first 4 steps, followed by a more
      gradual rise with successive stepping. Neither the electromyographic activity of
      the elbow flexor nor that of the extensor muscles was related to that flexion
      movement. The excursion into flexion on the non-paretic side was smaller than on
      the paretic side and incorporated flexion-extension fluctuations. The associated
      reaction at the paretic elbow during walking is a postural response which is
      triggered by the balance perturbation in the gait activity. It starts with a
      steep rise in flexion which seems to be reflexive in nature. The preservation of
      elbow flexion during walking may be an expression of stiffening of the elbow
      flexor muscles fibers.

PMID- 9020822
TI  - Anticipatory postural adjustments during self-initiated perturbations of
      different magnitude triggered by a standard motor action.
AB  - The purpose of the study was to define whether anticipatory postural adjustments
      scale with the magnitude of a self-triggered postural perturbation when a
      standard motor action triggers the perturbation. Standing subjects generated
      vertical forces of different magnitude with their extended arms against a bar
      connected through a rigid cord to the floor. They released the bar with a
      standard bilateral shoulder abduction. Anticipatory postural adjustments were
      seen as changes in the level and/or timing of the background activation of
      postural muscles. Muscles of the dorsal part of the legs and of the trunk
      demonstrated an anticipatory decrease in the level of activation, commonly
      leading to its complete disappearance. There was no relation between the
      magnitude of the unloading and the timing of the changes in the background
      activity of these muscles. Muscles of the frontal part of the legs and of the
      trunk demonstrated an anticipatory increase in their activity whose timing and
      amplitude correlated positively with the magnitude of the perturbation. We
      conclude that anticipatory postural adjustments can be scaled with respect to the
      magnitude of a self-triggered perturbation.

PMID- 9020823
TI  - Postpulse effects on blink reflex responses.
AB  - The technique of paired stimulation is routinely used in many laboratories in the
      assessment of the excitability recovery curve of the blink reflex. Other effects,
      such as prepulse inhibition or classical conditioning, can also be investigated
      with repeated presentation of pairs of time-locked stimuli. Regularly repeated
      presentations of an unpleasant stimulus may give rise to a transient excitability
      enhancement in neural structures in the reflex circuit. We have investigated
      whether such a transient shift in excitability can be demonstrated before the
      actual stimulus is applied. In 10 normal volunteers, we regularly alternated
      series of 5 trials containing an auditory tone of mild intensity with series of
      the same auditory tone followed by a relatively strong supraorbital nerve
      electrical stimulus. We calculated the habituation percentage of the orbicularis
      oculi responses to the auditory stimulus within a series and compared the results
      obtained in series containing the auditory tone alone with those from series
      containing the auditory tone followed by the electrical stimulus. Habituation was
      significantly less with paired stimulation than with the auditory tone alone, the
      mean area of the response to the 3rd trial in percentage of that to the first
      trial being 34.0 +/- 16.4% for paired stimuli, and 20.3 +/- 14.1% for auditory
      stimulus alone (P = 0.008). This effect, induced by the presence of an impending
      electrical stimulus on the response to a preceding stimulus, is defined as a
      postpulse effect in contradistinction to the prepulse effects induced by a weak
      stimulus on the response to a subsequent startle-eliciting stimulus. When a
      paradigm with a stimulus pair is used in human subjects, the possibility of
      effects occurring in both temporal directions should be taken into account. Blink
      reflex responses to a given stimulus may exhibit excitability changes induced by
      a preceding or by an impending stimulus.

PMID- 9020824
TI  - A comparison of computer-based methods for the determination of onset of muscle
      contraction using electromyography.
AB  - Little consensus exists in the literature regarding methods for determination of
      the onset of electromyographic (EMG) activity. The aim of this study was to
      compare the relative accuracy of a range of computer-based techniques with
      respect to EMG onset determined visually by an experienced examiner. Twenty-seven
      methods were compared which varied in terms of EMG processing (low pass filtering
      at 10, 50 and 500 Hz), threshold value (1, 2 and 3 SD beyond mean of baseline
      activity) and the number of samples for which the mean must exceed the defined
      threshold (20, 50 and 100 ms). Three hundred randomly selected trials of a
      postural task were evaluated using each technique. The visual determination of
      EMG onset was found to be highly repeatable between days. Linear regression
      equations were calculated for the values selected by each computer method which
      indicated that the onset values selected by the majority of the parameter
      combinations deviated significantly from the visually derived onset values.
      Several methods accurately selected the time of onset of EMG activity and are
      recommended for future use.

PMID- 9020825
TI  - A system-based study of the variation in the amplitude of the compound sensory
      nerve action potential recorded using surface electrodes.
AB  - This study arose from the impression that there is a wide variation in the
      amplitude of the compound sensory nerve action potential (SNAP) when recorded
      using surface electrodes. Both the physiological factors influencing the SNAP and
      the method of measurement itself can be viewed as inputs to a system that
      produces the recorded value as its output. Taking a systems approach to the
      analysis of the variation in the recorded value of the SNAP on repeat testing,
      the techniques of statistical process control and experimental design were used
      to study three electrodes. All showed wide variation of the results in a single
      control subject. Many different factors were studied but no single factor was
      found to be the cause for a significant amount of the variation. This finding,
      coupled to the wide variation demonstrated, has implications for the use of
      surface recording of the SNAP.

PMID- 9020826
TI  - Significance of A-waves recorded in routine motor nerve conduction studies.
AB  - The occurrence of A-waves during routine F-wave studies was investigated in 556
      consecutive patients referred to the Department of Clinical Neurophysiology at
      the University Hospital in Uppsala for various neuromuscular disorders.
      Altogether, 2367 nerves in the upper and lower extremities were studied. An A
      wave, with a nearly constant latency and a uniform shape on consecutive
      stimulations, could be recorded in 184 nerves (7.8%) out of 124 patients (22.3%).
      More than 50% of patients with A-waves had various types of polyneuropathies. Of
      all patients with polyneuropathy, 65% had at least one nerve with A-waves. A
      waves occurred somewhat less frequently in patients with radiculopathies. In
      other proximal local nerve lesions they were found less often and only
      exceptionally in patients with distal nerve lesions. A-waves were present in 6
      out of 10 patients with motor neurone diseases. There was no correlation between
      the number of A-waves found in one nerve or the number of nerves in a given
      patient with A-waves and the aetiology or severity of the underlying disease. A
      waves were found in 11 patients referred for various neurological symptoms in
      whom other neurophysiological findings were normal. This might be interpreted as
      an early sign of underlying disease because in 100 healthy controls no A-waves
      could be elicited, with the exception of 3 subjects who had A-waves in the
      abductor hallucis muscle when the tibial nerve was stimulated. We conclude that
      the appearance of A-waves should be considered a sign of either a local nerve
      lesion or a generalised neuropathy in all other nerves except for the tibial
      nerve.

PMID- 9020827
TI  - The effects of cortical stimulation, anesthesia and recording site on
      somatosensory evoked potentials in the rat.
AB  - The purpose of this study was to standardize the method of spinal cord monitoring
      with evoked potentials in the rat. Seventeen male Wistar rats were anesthetized
      with alpha-chloralose and urethane. Somatosensory evoked potential (SEP) and
      cerebellar evoked potential (CEP) following sciatic nerve stimulation were mapped
      at different time points after induction of anesthesia. SEP peaks at latencies of
      13-18 ms (P13, N18) were localized to an extremely small area over the sensory
      cortex. In contrasts, a negative peak of the SEP at 11 ms (N11) and the CEP were
      widely distributed over the cerebral or cerebellar surface. Anesthesia
      significantly influenced the cortical components of the SEP. In 10 rats, MEP or
      posterior fossa evoked potential (PFEP) following stimulation of the sensorimotor
      or cerebellar cortices respectively, were recorded at T9. Stimulation of
      different points produced little change on the waveforms of the MEP or PFEP.
      Successive recordings of MEP and SEP revealed that the P13-N18 complex of the SEP
      was markedly suppressed after MEP recordings were made. In conclusion, this study
      identified several factors which alter SEP waveforms in the rat including
      location of recording, anesthesia and sequence with respect to MEP recording. MEP
      by stimulation of the same sensory cortex as SEP recordings should not be used
      for concurrent monitoring, since cortical stimulation will change the waveforms
      of the SEP.

PMID- 9020828
TI  - Entering the total-genomic era.

PMID- 9020829
TI  - KVLQT1, the rhythm of imprinting.

PMID- 9020830
TI  - Insights from a lost visual pigment.

PMID- 9020831
TI  - Hox genes, arms and the man.

PMID- 9020832
TI  - Anticipating anticipation.

PMID- 9020833
TI  - IGF2 is parentally imprinted in human preimplantation embryos.

PMID- 9020834
TI  - Cholesterol, hedgehog and embryogenesis.

PMID- 9020835
TI  - International collaboration in genetics research.

PMID- 9020836
TI  - Structure and function in gene patenting.
AB  - The United States patent system treats DNA sequences as large chemical compounds
      in determining their patentability. This approach has been helpful to those who
      seek to patent previously unidentified DNA sequences, but it may prove less
      advantageous from the perspective of those who elucidate biological functions and
      disease relevance of previously identified genes. A current controversy over
      patent rights for DNA sequences encoding leptin receptors provides a useful case
      study for illustrating some of the issues that are likely to arise in applying
      doctrine derived from chemical patent cases in the context of gene discovery.

PMID- 9020837
TI  - A human candidate spermatogenesis gene, RBM1, is conserved and amplified on the
      marsupial Y chromosome.
AB  - Three genes, RBM1, DAZ and TSPY, map to a small region of the long arm of the
      human Y chromosome which is deleted in azoospermic men. RBM1, but not DAZ or
      TSPY, has a Y-linked homologue in marsupials which is transcribed in the testis.
      This suggests that RBM1 has been retained on the Y chromosome because of a
      critical male-specific function. Marsupial RBM1 is closely related to human RBM1,
      but, like the related autosomal gene hnRNPG, lacks the amplification of an exon.
      This suggests that RBM1 evolved from hnRNPG at least 130 million years ago and
      has undergone internal amplification in primates, as well as independent
      amplification in several therian [corrected] lineages.

PMID- 9020838
TI  - Complete inventory of the yeast ABC proteins.
AB  - The complete sequence of the yeast genome predicts the existence of 29 proteins
      belonging to the ubiquitous ATP-binding cassette (ABC) superfamily. Using binary
      comparison, phylogenetic classification and detection of conserved amino acid
      residues, the yeast ABC proteins have been classified in a total of six clusters,
      including ten subclusters of distinct predicted topology and presumed distinct
      function. Study of the yeast ABC proteins provides insight into the physiological
      function and biochemical mechanisms of their human homologues, such as those
      involved in cystic fibrosis, adrenoleukodystrophy, Zellweger syndrome, multidrug
      resistance and the antiviral activity of interferons.

PMID- 9020839
TI  - Functional transplant of megabase human immunoglobulin loci recapitulates human
      antibody response in mice.
AB  - We constructed two megabase-sized YACs containing large contiguous fragments of
      the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly
      germline configuration, including approximately 66 VH and 32 V kappa genes. We
      introduced these YACs into Ig-inactivated mice and observed human antibody
      production which closely resembled that seen in humans in all respects, including
      gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with
      somatic hypermutation enables the mice to generate high affinity fully human
      antibodies to multiple antigens, including human proteins. Our results underscore
      the importance of the large Ig fragments with multiple V genes for restoration of
      a normal humoral immune response. These mice are likely to be a valuable tool for
      the generation of therapeutic antibodies.

PMID- 9020840
TI  - A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal
      (BOR) syndrome and identifies a novel gene family.
AB  - A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at
      chromosome 8q13.3 by positional cloning and shown to underlie the disease. This
      gene is a human homologue of the Drosophila eyes absent gene (eya), and was
      therefore called EYA1. A highly conserved 271-amino acid C-terminal region was
      also found in the products of two other human genes (EYA2 and EYA3),
      demonstrating the existence of a novel gene family. The expression pattern of the
      murine EYA1 orthologue, Eya1, suggests a role in the development of all
      components of the inner ear, from the emergence of the otic placode. In the
      developing kidney, the expression pattern is indicative of a role for Eya1 in the
      metanephric cells surrounding the 'just-divided' ureteric branches.

PMID- 9020841
TI  - Characterization of the full fragile X syndrome mutation in fetal gametes.
AB  - Fragile X syndrome results from the expansion of the CGG repeat in the FMR1 gene.
      Expansion has been suggested to be a postzygotic event with the germline
      protected. From an analysis of intact ovaries of full mutation fetuses, we now
      show that only full expansion alleles can be detected in oocytes (but in the
      unmethylated state). Similarly, the testes of a 13-week full mutation fetus show
      no evidence of premutations while a 17-week full mutation fetus exhibits some
      germ cells with attributes of premutations. These data discount the hypothesis
      that the germline is protected from full expansion and suggest full mutation
      contraction in the immature testis. Thus, full expansion may already exist in the
      maternal oocyte, or postzygotic expansion, if it occurs, arises quite early in
      development prior to germline segregation.

PMID- 9020843
TI  - Defects in the rhodopsin kinase gene in the Oguchi form of stationary night
      blindness.
AB  - Oguchi disease is a recessively inherited form of stationary night blindness due
      to malfunction of the rod photoreceptor mechanism. Patients with this disease
      show a distinctive golden-brown colour of the fundus that occurs as the retina
      adapts to light, called the Mizuo phenomenon. Recently a defect in arrestin, a
      member of the rod phototransduction pathway, was found to cause this disease in
      some Japanese patients. As rhodopsin kinase works with arrestin in shutting off
      rhodopsin after it has been activated by a photon of light, it is reasonable to
      propose that some cases of Oguchi disease might be caused by defects in rhodopsin
      kinase. This report describes an analysis of the arrestin and rhodopsin kinase
      genes in three unrelated cases of Oguchi disease. No defects in arrestin were
      detected, but all three cases had mutations in the rhodopsin kinase gene. Two
      cases were found to be homozygous for a deletion encompassing exon 5, predicted
      to lead to a nonfunctional protein. The third case was a compound heterozygote
      with two allelic mutations, a missense mutation (Val380Asp) affecting a residue
      in the catalytic domain, and a frameshift mutation (Ser536(4-bp del)) resulting
      in truncation of the carboxy terminus. Our results indicate that null mutations
      in the rhodopsin kinase gene are a cause of Oguchi disease and extend the known
      genetic heterogeneity in congenital stationary night blindness.

PMID- 9020842
TI  - Promoter swapping between the genes for a novel zinc finger protein and beta
      catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations.
AB  - Pleiomorphic adenoma of the salivary glands is a benign epithelial tumour
      occurring primarily in the major and minor salivary glands. It is by far the most
      common type of salivary gland tumour. Microscopically, pleiomorphic adenomas show
      a marked histological diversity with epithelial, myoepithelial and mesenchymal
      components in a variety of patterns. In addition to a cytogenetic subgroup with
      normal karyotypes, pleiomorphic adenomas are characterized by recurrent
      chromosome rearrangements, particularly reciprocal translocations, with
      breakpoints at 8q12, 3p21, and 12q13-15, in that order of frequency. The most
      common abnormality is a reciprocal t(3;8)(p21;q12). We here demonstrate that the
      t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel,
      developmentally regulated zinc finger gene at 8q12, and the constitutively
      expressed gene for beta-catenin (CTNNB1), a protein interface functioning in the
      WG/WNT signalling pathway and specification of cell fate during embryogenesis.
      Fusions occur in the 5'-non-coding regions of both genes, exchanging regulatory
      control elements while preserving the coding sequences. Due to the
      t(3;8)(p21;q12), PLAG1 is activated and expression levels of CTNNB1 are reduced.
      Activation of PLAG1 was also observed in an adenoma with a variant translocation
      t(8;15)(q12;q14). Our results indicate that PLAG1 activation due to promoter
      swapping is a crucial event in salivary gland tumourigenesis.

PMID- 9020844
TI  - Mutation of HOXA13 in hand-foot-genital syndrome.
AB  - There are several human syndromes which involve defects of the limbs and the
      Mullerian ducts or its derivatives. The hand-foot-genital (HFG) syndrome is an
      autosomal dominant, fully penetrant disorder that was originally described by
      Stern et al. Additional reports describing other affected families have also been
      published. Limb anomalies include short first metacarpals of normal thickness,
      small distal phalanges of the thumbs, short middle phalanges of the fifth
      fingers, and fusion or delayed ossification of wrist bones. In the feet, the
      great toe is shorter due to a short first metatarsal and a small, pointed distal
      phalanx. Uterine anomalies are common in females with HFG, and typically involve
      a partially divided (bicornuate) or completely divided (didelphic) uterus,
      representing defects of Mullerian duct fusion. Urinary tract malformations in
      affected HFG females include a displaced urethral opening and malposition of
      ureteral orifices in the bladder wall; affected males may have hypospadias
      (ventrally misplaced urethral opening) of variable severity. We report the
      identification of a HOXA13 nonsense mutation in a family with hand-foot-genital
      syndrome. The mutation converts a highly conserved tryptophan residue in the
      homeodomain to a stop codon, which truncates 20 amino acids from the protein and
      likely eliminates or greatly reduces the ability of the protein to bind to DNA.

PMID- 9020845
TI  - Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith
      Wiedemann syndrome chromosomal rearrangements.
AB  - Genomic imprinting is an epigenetic chromosomal modification in the gamete or
      zygote causing preferential expression of a specific parental allele in somatic
      cells of the offspring. We and others have identified three imprinted human genes
      on 11p15.5, IGF2, H19, and p57KIP2, although the latter gene is separated by 700
      kb from the other two, and it is unclear whether there are other imprinted genes
      within this large interval. We previously mapped an embryonal tumour suppressor
      gene to this region, as well as five balanced germline chromosomal rearrangement
      breakpoints from patients with Beckwith-Wiedemann syndrome (BWS), a condition
      characterized by prenatal overgrowth and cancer. We isolated the upstream exons
      of the previously identified gene KVLQT1, which causes the familial cardiac
      defect long-QT (LQT) syndrome. We found that KVLQT1 spans much of the interval
      between p57KIP2 and IGF2, and that it is also imprinted. We demonstrated that the
      gene is disrupted by chromosomal rearrangements in BWS patients, as well as by a
      balanced chromosomal translocation in an embryonal rhabdoid tumour. Furthermore,
      the lack of parent-of-origin effect in LQT syndrome appears to be due to relative
      lack of imprinting in the affected tissue, cardiac muscle, representing a novel
      mechanism for variable penetrance of a human disease gene.

PMID- 9020846
TI  - A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and
      Lange-Nielsen cardioauditory syndrome.
AB  - The Jervell and Lange-Nielsen (JLN) syndrome (MIM 220400) is an inherited
      autosomal recessive disease characterized by a congenital bilateral deafness
      associated with a QT prolongation on the electrocardiogram, syncopal attacks due
      to ventricular arrhythmias and a high risk of sudden death. JLN syndrome is a
      rare disease, which seems to affect less than one percent of all deaf children.
      Linkage to chromosome 11p15.5 markers was found by analysing four consanguinous
      families. Recombinants allowed us to map the JLN gene between D11S922 and
      D11S4146, to a 6-cM interval where KVLQT1, a potassium channel gene causing
      Romano-Ward (RW) syndrome, the dominant form of long QT syndrome, has been
      previously localized. An homozygous deletion-insertion event (1244, -7 +8) in the
      C-terminal domain of this gene was detected in three affected children of two
      families. We found that KVLQT1 is expressed in the stria vascularis of mouse
      inner ear by in situ hybridization. Taken together, our data indicate that KVLQT1
      is responsible for both JLN and RW syndromes and has a key role not only in the
      ventricular repolarization but also in normal hearing, probably via the control
      of endolymph homeostasis.

PMID- 9020847
TI  - Moderate intergenerational and somatic instability of a 55-CTG repeat in
      transgenic mice.
AB  - Myotonic dystrophy (DM) is associated with the expansion of a (CTG)n
      trinucleotide repeat in the 3' untranslated region (UTR) of the DM protein kinase
      gene (DMPK). The (CTG)n repeat is polymorphic and varies in size between 5 and 37
      repeats in unaffected individuals whereas in affected patients there are between
      50 and 4,000 CTGs. The size of the (CTG)n repeat, which increases through
      generations, generally correlates with clinical severity and age of onset. The
      instability of the CTG repeat appears to depend on its size as well as on the sex
      of the transmitting parent. Moreover, mitotic instability analysis of different
      human DM tissues shows length mosaicism between different cell lineages. The
      molecular mechanisms of triplet instability remain elusive. To investigate the
      role of genomic sequences in instability, we produced transgenic mice containing
      a 45-kb genomic segment with a 55-CTG repeat cloned from a mildly affected
      patient. In contrast to other mouse models containing CAG repeats within cDNAs,
      these mice showed both intergenerational and somatic repeat instability.

PMID- 9020848
TI  - Hypermutable myotonic dystrophy CTG repeats in transgenic mice.
AB  - Myotonic dystrophy (DM) is one of a growing number of inherited human disorders
      associated with the expansion of triplet repeat DNA sequences. Expanded alleles
      are highly unstable in both the germline and soma, accounting in large part for
      the unusual genetics of this disorder, its phenotypic variability and probably,
      the progressive nature of the symptoms. However, the molecular mechanisms and the
      genetic factors modulating repeat stability in DM and the other human disorders
      associated with expanded repeats are not well understood. To provide a model
      system in which the turnover of triplet repeats could be studied throughout
      mammalian development, we have generated five transgenic mouse lines
      incorporating expanded CTG/CAG arrays derived from the human DM locus. Transgene
      analysis has revealed germline hypermutability, including expansions, deletions
      and parent-of-origin effects, somatic and early embryonic instability and
      segregation distortion. Mutational differences between lines and sexes
      demonstrate that stability, as in humans, is modulated by as yet unidentified cis
      and trans acting genetic elements.

PMID- 9020849
TI  - Instability of highly expanded CAG repeats in mice transgenic for the
      Huntington's disease mutation.
AB  - Six inherited neurodegenerative diseases are caused by a CAG/polyglutamine
      expansion, including spinal and bulbar muscular atrophy (SBMA), Huntington's
      disease (HD), spinocerebellar ataxia type 1 (SCA1), dentatorubral pallidoluysian
      atrophy (DRPLA) Machado-Joseph disease (MJD or SCA3) and SCA2. Normal and
      expanded HD allele sizes of 6-39 and 35-121 repeats have been reported, and the
      allele distributions for the other diseases are comparable. Intergenerational
      instability has been described in all cases, and repeats tend to be more unstable
      on paternal transmission. This may present as larger increases on paternal
      inheritance as in HD, or as a tendency to increase on male and decrease on female
      transmission as in SCA1 (ref. 15). Somatic repeat instability is also apparent
      and appears most pronounced in the CNS. The major exception is the cerebellum,
      which in HD, DRPLA, SCA1 and MJD has a smaller repeat relative to the other brain
      regions tested. Of non-CNS tissues, instability was observed in blood, liver,
      kidney and colon. A mouse model of CAG repeat instability would be helpful in
      unravelling its molecular basis although an absence of CAG repeat instability in
      transgenic mice has so far been reported. These studies include (CAG) in the
      androgen receptor cDNA, (CAG) in the HD cDNA, (CAG) in the SCA1 cDNA, (CAG) in
      the SCA3 cDNA and as an isolated (CAG) tract.

PMID- 9020850
TI  - Follicle stimulating hormone is required for ovarian follicle maturation but not
      male fertility.
AB  - Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family
      that includes luteinzing hormone (LH), thyroid stimulating hormone, and chorionic
      gonadotropin. These heterodimeric hormones share a common alpha subunit and
      differ in their hormone-specific beta subunit. The biological activity is
      conferred only by the heterodimers. FSH and LH are synthesized in the same cells
      of the pituitary, the gonadotrophs. FSH receptors are localized to Sertoli cells
      of the testes and granulosa cells of the ovary. Minimal data has been accumulated
      so far involving human mutations in the FSH beta, LH beta, or the gonadotropin
      receptor genes. There are no known mouse strains with mutations in the FSH beta
      gene. To generate animal models for human diseases involving the gonadotropin
      signal transduction pathway, we produced mice deficient in the FSH beta subunit
      and therefore in FSH using ES cell technology. FSH-deficient females are
      infertile due to a block in folliculogenesis prior to antral follicle formation.
      Although FSH was predicted to be necessary for spermatogenesis and Sertoli cell
      growth in males, FSH-deficient males are fertile despite having small testes. Our
      findings have important implications for male contraceptive development in
      humans.

PMID- 9020851
TI  - Men homozygous for an inactivating mutation of the follicle-stimulating hormone
      (FSH) receptor gene present variable suppression of spermatogenesis and
      fertility.
AB  - Gonadal function is controlled by the two pituitary gonadotropins, luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH). While LH mainly regulates
      gonadal steroidogenesis, FSH is considered essential for folliculogenesis in the
      female and spermatogenesis in the male. We recently discovered that an
      inactivating point mutation in the FSH receptor (R) gene causes a recessively
      inherited form of hypergonadotropic ovarian failure in homozygous females. This
      566C-->T mutation, predicting an alanine to valine substitution, is located in
      exon 7 of the FSHR gene, in the region encoding the extracellular domain of the
      receptor molecule. Functional testing showed a clear-cut reduction in ligand
      binding and signal transduction by the mutated receptor. Hence, lack of FSH
      function is incompatible with ovarian follicular maturation and female fertility.
      In the male, FSH is generally considered essential for the pubertal initiation of
      spermatogenesis and maintenance of quantitatively normal sperm production in
      adults. We report here the first characterization of males homozygous for an
      inactivating FSHR mutation. They have variable degrees of spermatogenic failure,
      but, surprisingly, do not show azoospermia or absolute infertility. These results
      question the essential role of FSH for the initiation of spermatogenesis, and
      demonstrate that FSH is more important for female than for male fertility.

PMID- 9020852
TI  - Mapping of a major genetic modifier of embryonic lethality in TGF beta 1 knockout
      mice.
AB  - The transforming growth factor beta 1 (TGF beta 1) signalling pathway is
      important in embryogenesis and has been implicated in hereditary haemorrhagic
      telangiectasia (HHT), atherosclerosis, tumorigenesis and immunomodulation.
      Therefore, identification of factors which modulate TGF beta 1 bioactivity in
      vivo is important. On a mixed genetic background, approximately 50% Tgfb1-/-
      conceptuses die midgestation from defective yolk sac vasculogenesis. The other
      half are developmentally normal but die three weeks postpartum. Intriguingly, the
      vascular defects of Tgfb1-/- mice share histological similarities to lesions seen
      in HHT patients. It has been suggested that dichotomy in Tgfb1-/- lethal
      phenotypes is due to maternal TGF beta 1 rescue of some, but not all, Tgfb1-/-
      embryos12. Here we show that the Tgfb1-/- phenotype depends on the genetic
      background of the conceptus. In NIH/Ola, C57BL/6J/Ola and F1 conceptuses, Tgfb1-/
      lethality can be categorized into three developmental classes. A major
      codominant modifier gene of embryo lethality was mapped to proximal mouse
      chromosome 5, using a genome scan for non-mendelian distribution of alleles in
      Tgfb1-/- neonatal animals which survive prenatal lethality. This gene accounts
      for around three quarters of the genetic effect between mouse strains and can, in
      part, explain the distribution of the three lethal phenotypes. This approach,
      using neonatal DNA samples, is generally applicable to identification of loci
      that influence the effect of early embryonic lethal mutations, thus furthering
      knowledge of genetic interactions that occur during early mammalian development
      in vivo.

PMID- 9020853
TI  - Selective inhibition of mutant human mitochondrial DNA replication in vitro by
      peptide nucleic acids.
AB  - Mitochondrila DNA (mtDNA) is the only extrachromosomal DNA in humans. It is a
      small (16.5 kb) genome which encodes 13 essential peptides of the respiratory
      chain, two rRNAs and 22 tRNAs. Defects of this genome are now recognized as
      important causes of disease and may take the form of point mutations or
      rearrangements. There is no effective treatment for patients with mtDNA
      mutations. In the majority of patients with mtDNA defects, both mutant and wild
      type molecules are present in the same cell-a phenomenon known as intracellular
      heteroplasmy. In addition, in the presence of heteroplasmy there is a threshold
      whereby a certain level of mutant mtDNA is necessary before the disease becomes
      biochemically and clinically apparent. Based on the presence of heteroplasmy and
      the recessive nature of these mutations, we believe it will be possible to treat
      patients by selectively inhibiting the replication of the mutant mtDNA, thereby
      allowing propagation of only the wild-type molecule. To confirm the validity of
      such an approach we synthesised peptide nucleic acids (PNAs) complementary to
      human mtDNA templates containing a deletion breakpoint or single base mutation,
      both mutations well documented to cause disease. Using an in vitro replication
      run-off assay under physiological conditions, the antigenomic PNAs specifically
      inhibited replication of mutant but not wild-type mtDNA templates. Furthermore,
      we have shown uptake of these PNAs into cultured human myoblasts. We believe that
      we have therefore established the potential value of antigenomic PNA therapy for
      patients with heteroplasmic mtDNA disorders.

PMID- 9020854
TI  - Retinopathy induced in mice by targeted disruption of the rhodopsin gene.
AB  - Retinitis pigmentosa (RP) represents the most common mendelian degenerative
      retinopathy of man, involving death of rod photoreceptors, cone cell
      degeneration, retinal vessel attenuation and pigmentary deposits. The patient
      experiences night blindness, usually followed by progressive loss of visual
      field. Genetic linkage between an autosomal dominant RP locus and rhodopsin, the
      photoreactive pigment of the rod cells, led to the identification of mutations
      within the rhodopsin gene in both dominant and recessive forms of RP. To better
      understand the functional and structural role of rhodopsin in the normal retina
      and in the pathogenesis of retinal disease, we generated mice carrying a targeted
      disruption of the rhodopsin gene. Rho-/- mice do not elaborate rod outer
      segments, losing their photoreceptors over 3 months. There is no rod ERG response
      in 8-week-old animals. Rho+/- animals retain the majority of their photoreceptors
      although the inner and outer segments of these cells display some structural
      disorganization, the outer segments becoming shorter in older mice. These animals
      should provide a useful genetic background on which to express other mutant opsin
      transgenes, as well as a model to assess the therapeutic potential of re
      introducing functional rhodopsin genes into degenerating retinal tissues.

PMID- 9020856
TI  - Modulation of muscle creatine kinase promoter activity by the inducible orphan
      nuclear receptor TIS1.
AB  - TIS1, an inducible orphan nuclear receptor, was originally isolated as a tumour
      promoter-inducible gene in mouse 3T3 cells and later shown to be induced by
      growth factors and other extracellular stimuli. We show here that TIS1 mRNA was
      expressed in proliferating C2C12 mouse skeletal muscle cells out that the level
      of TIS1 expression increased during muscle differentiation. Overexpression of
      TIS1 transactivated muscle creatine kinase (MCK) reporter genes containing as
      little as 80 bp of the proximal 5' flanking region. In contrast, a promoterless
      TIS1 construct and a frameshift mutant TIS1 construct were unable to
      transactivate the MCK reporter gene. Moreover, the effect exerted by TIS1
      appeared to be selective for the MCK promoter. Treatment of C2C12 cells with
      forskolin, which is known to induce TIS1 expression, also stimulated MCK reporter
      gene activity. Interestingly, in vitro translated TIS1 protein failed to bind to
      the MCK promoter region, suggesting that the transactivation effect of TIS1 may
      be mediated without direct interaction of the protein with the MCK promoter DNA.
      Collectively, these results suggest that changing levels of TIS1 may help to
      modulate the expression of MCK, and perhaps other muscle-specific genes, in
      response to physiological changes.

PMID- 9020855
TI  - Membrane protein secretases.
AB  - A diverse range of membrane proteins of Type 1 or Type II topology also occur as
      a circulating, soluble form. These soluble forms are often derived from the
      membrane form by proteolysis by a group of enzymes referred to collectively as
      'secretases' or 'sheddases'. The cleavage generally occurs close to the
      extracellular face of the membrane, releasing physiologically active protein.
      This secretion process also provides a mechanism for down-regulating the protein
      at the cell surface. Examples of such post-translational proteolysis are seen in
      the Alzheimer's amyloid precursor protein, the vasoregulatory enzyme angiotensin
      converting enzyme, transforming growth factor-alpha, the tumour necrosis factor
      ligand and receptor superfamilies, certain cytokine receptors, and others. Since
      the proteins concerned are involved in pathophysiological processes such as
      neurodegeneration, apoptosis, oncogenesis and inflammation, the secretases could
      provide novel therapeutic targets. Recent characterization of these individual
      secretases has revealed common features, particularly sensitivity to certain
      metalloprotease inhibitors and upregulation of activity by phorbol esters. It is
      therefore likely that a closely related family of metallosecretases controls the
      surface expression of multiple integral membrane proteins. Current knowledge of
      the various secretases are compared in this Review, and strategies for cell-free
      assays of such proteases are outlined as a prelude to their ultimate purification
      and cloning.

PMID- 9020857
TI  - Ktr1p is an alpha-1,2-mannosyltransferase of Saccharomyces cerevisiae. Comparison
      of the enzymic properties of soluble recombinant Ktr1p and Kre2p/Mnt1p produced
      in Pichia pastoris.
AB  - The yeast genome contains a KRE2/MNT1 family of nine related genes with amino
      acid similarity to the alpha 1,2-mannosyltransferase Kre2p/Mnt1p, the only member
      of this family whose enzymic properties have been studied. In this study, the
      enzymic properties of Ktr1p, another member of this family, were studied and
      compared to those of Kre2p/Mnt1p. Recombinant soluble forms of Kre2p/Mnt1p and
      Ktr1p lacking their N-terminal regions were expressed as secreted proteins from
      the methylotrophic yeast Pichia pastoris. After induction with methanol, the
      medium contained approx, 40 and 400 mg/l of soluble recombinant Kre2p/Mnt1p and
      Ktr1p respectively. Both recombinant proteins were shown to exhibit alpha 1,2
      mannosyltransferase activity. The enzymes have an absolute requirement for Mn2+
      and a similar K(m) for mannose (280-350 mM), methyl-alpha-mannoside (60-90 mM)
      and GDP-mannose (50-90 microM), but the Vmax was approx. 10 times higher for
      Kre2p/Mnt1p than for Ktr1p. The enzymes have similar substrate specificities and
      utilize mannose, methyl-alpha-mannoside, alpha-1,2-mannobiose and methyl-alpha
      1,2-mannobiose, as well as Man15-30GlcNAc, derived from mnn2 mutant
      glycoproteins, as substrates. The enzymes do not utilize alpha-1,6-mannobiose,
      alpha-1,6-mannotriose, alpha-1,6-mannotetraose, mammalian Man9GlcNAc or yeast
      Man9-10GlcNAc. These results indicate that Kre2p/ Mnt1p and Ktr1p are capable of
      participating in both N-glycan and O-glycan biosynthesis.

PMID- 9020858
TI  - Human tissue non-specific alkaline phosphatases: sugar-moiety-induced enzymic and
      antigenic modulations and genetic aspects.
AB  - To investigate the possible role(s) of glycans in human tissue non-specific
      alkaline phosphatase (TNAP) activity, the iso-enzymes were purified and treated
      with various exo- and endo-glycosidases. Catalytic activity, oligomerization,
      conformation and immunoreactivity of the modified TNAPs were evaluated. All TNAPs
      proved to be N-glycosylated, and only the liver isoform (LAP) is not O
      glycosylated. Usually, the kidney (KAP) and bone (BAP) isoenzymes are similar and
      cannot be clearly discriminated. Differences between the immunoreactivity of
      KAP/BAP and LAP with a BAP antibody were mainly attributed to the N-glycosylated
      moieties of the TNAPs. In addition, elimination of O-glycosylations moderately
      affects the TNAP reactivity. Interestingly, N-glycosylation is absolutely
      essential for TNAP activity, but not for that of the placental or intestinal
      enzymes. According to the deduced amino acid sequence of TNAP cDNA, Asn-213 is a
      possible N-glycosylation site, and our present findings suggest that this sugar
      chain plays a key role in enzyme regulation. With regard to the oligomeric state
      of alkaline phosphatase (AP) isoforms, the dimer/tetramer equilibrium is
      dependent on the deglycosylation of glycosyl-phosphatidylinositol(GPI)-free APs,
      but not GPI-linked APs. This equilibrium does not affect the AP conformation as
      observed with CD. With regard to TNAPs, no data were available on the gene
      expression or nature of the 5'-non-translated leader exon of human KAP, as
      opposed to BAP and LAP genes. cDNA sequencing revealed that cortex/medulla KAP is
      genetically related to BAP, and medulla KAP to LAP.

PMID- 9020859
TI  - Comparative studies of rat recombinant purple acid phosphatase and bone tartrate
      resistant acid phosphatase.
AB  - The tartrate-resistant acid phosphatase (TRAP) of rat osteoclasts has been shown
      to exhibit high (85-94%) identity at the amino acid sequence level with the
      purple acid phosphatase (PAP) from bovine spleen and with pig uteroferrin. These
      iron-containing purple enzymes contain a binuclear iron centre, with a tyrosinate
      to-Fe(III) charge-transfer transition responsible for the purple colour. In the
      present study, production of rat osteoclast TRAP could be achieved at a level of
      4.3 mg/litre of medium using a baculovirus expression system. The enzyme was
      purified to apparent homogeneity using a combination of cation-exchange,
      hydrophobic-interaction, lectin-affinity and gel-permeation chromatography steps.
      The protein as isolated had a purple colour, a specific activity of 428 units/mg
      of protein and consisted of the single-chain form of molecular mass 34 kDa, with
      only trace amounts of proteolytically derived subunits. The recombinant enzyme
      had the ability to dephosphorylate bone matrix phosphoproteins, as previously
      shown for bone TRAP. Light absorption spectroscopy of the isolated purple enzyme
      showed a lambda max at 544 nm, which upon reduction with ascorbic acid changed to
      515 nm, concomitant with the transition to a pink colour. EPR spectroscopic
      analysis of the reduced enzyme at 3.6 K revealed a typical mu-hydr(oxo)-bridged
      mixed-valent Fe(II)Fe(III) signal with g-values at 1.96, 1.74 and 1.60, proving
      that recombinant rat TRAP belongs to the family of PAPs. To validate the use of
      recombinant PAP in substituting for the rat bone counterpart in functional
      studies, various comparative studies were carried out. The enzyme isolated from
      bone exhibited a lower K(m) for p-nitrophenyl phosphate and was slightly more
      sensitive to PAP inhibitors such as molybdate, tungstate, arsenate and phosphate.
      In contrast with the recombinant enzyme, TRAP from bone was isolated
      predominantly as the proteolytically cleaved, two-subunit, form. Both the
      recombinant enzyme and rat bone TRAP were shown to be substituted with N-linked
      oligosaccharides. A slightly higher apparent molecular mass of the monomeric form
      and N-terminal chain of bone TRAP compared with the recombinant enzyme could not
      be accounted for by differential N-glycosylation. Despite differences in specific
      post-translational modifications, the recombinant PAP should be useful in future
      studies on the properties and regulation of the mammalian PAP enzyme.

PMID- 9020860
TI  - Decarboxylation of malonyl-(acyl carrier protein) by 3-oxoacyl-(acyl carrier
      protein) synthases in plant fatty acid biosynthesis.
AB  - In order to identify regulatory steps in fatty acid biosynthesis, the influence
      of intermediate 3-oxoacyl-(acyl carrier proteins) (3-oxoacyl-ACPs) and end
      product acyl-ACPs of the fatty acid synthase reaction on the condensation
      reaction was investigated in vitro, using total fatty acid synthase preparations
      and purified 3-oxoacyl-ACP synthases (KASs; EC 2.3.1.41) from Cuphea lanceolata
      seeds. KAS I and II in the fatty acid synthase preparations were assayed for the
      elongation of octanoyl- and hexadecanoyl-ACP respectively, and the accumulation
      of the corresponding condensation product 3-oxoacyl-ACP was studied by modulating
      the content of the reducing equivalentS NADH and NADPH. Complete omission of
      reducing equivalents resulted with either KAS in the abnormal synthesis of acetyl
      ACP from malonyl-ACP by a decarboxylation reaction. Supplementation with NADPH or
      NADH, separately or in combination with recombinant 3-oxoacyl-ACP reductase (EC
      1.1.1.100), led to a decrease in the amount of acetyl-ACP and a simultaneous
      increase in elongation products. This demonstrates that the accumulation of 3
      oxoacyl-ACP inhibits the condensation reaction on the one hand, and induces the
      decarboxylation of malonyl-ACP on the other. By carrying out similar experiments
      with purified enzymes, this decarboxylation was attributed to the action of KAS.
      Our data point to a regulatory mechanism for the degradation of malonyl-ACP in
      plants which is activated by the accumulation of the fatty acid synthase
      intermediate 3-oxoacyl-ACP.

PMID- 9020861
TI  - Purification of a protein from Agrobacterium tumefaciens strain A348 that binds
      phenolic compounds.
AB  - In order to induce tumours on dicotyledonous plants, the bacterium Agrobacterium
      tumefaciens needs to be able to sense signal molecules, i.e. phenolic compounds.
      In order to identify putative chemoreceptors or environmental sensors involved in
      vir gene induction, we undertook the purification of a phenol-binding protein by
      affinity chromatography on a syringamide Ultrogel A4 column equilibrated at pH
      5.6. A mild extraction of bacterial proteins with a Tris/HCl buffer at pH 9.0 led
      to the purification of a 39 kDa protein (Pbp39) with a pl of 4.3 after specific
      elution of the affinity matrix with sodium syringate. When the affinity
      chromatography was performed at neutral pH, barely any protein was isolated,
      indicating the importance of an acidic pH for optimal affinity. A microplate
      binding experiment revealed that both syringlyl biotinylated-BSA and sinapyl
      biotinylated-BSA bound at pH 5.6 to the plate coated with Pbp39.

PMID- 9020863
TI  - Vanadium oxoanions and cAMP-dependent protein kinase: an anti-substrate
      inhibitor.
AB  - Vanadium oxoions have been shown to elicit a wide range of effects in biological
      systems, including an increase in the quantity of phosphorylated proteins. This
      response has been attributed to the inhibition of protein phosphatases, the
      indirect activation of protein kinases via stimulation of enzymes at early steps
      in signal transduction pathways and/or the direct activation of protein kinases.
      We have evaluated the latter possibility by exploring the effects of vanadate,
      decavanadate and vanadyl cation species on the activity of the cAMP-dependent
      protein kinase (PKA), a serine/threonine kinase. Vanadate, in the form of
      monomer, dimer, tetramer and pentamer species, neither inhibits nor activates
      PKA. In marked contrast, decavandate is a competitive inhibitor (Ki = 1.8 +/- 0.1
      mM) of kemptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly), a peptide-based substrate. This
      inhibition pattern is especially surprising, since the negatively charged
      decavanadate would not be predicted to bind to the region of the active site of
      the enzyme that accommodates the positively charged kemptide substrate. Our
      studies suggest that decavanadate can associate with kemptide in solution, which
      would prevent kemptide from interacting with the enzyme. Vanadium(IV) also
      inhibits the PKA-catalysed phosphorylation of kemptide, but with an IC50 of 366
      +/- 10 microM. However, in this case V4+ appears to bind to the Mg(2+)-binding
      site, since it can substitute for Mg2+. In the absence of Mg2+, the optimal
      concentration of vanadium(IV) for the PKA-catalysed phosphorylation of kemptide
      is 100 microM, with concentrations above 100 microM being markedly inhibitory.
      However, even at the optimal 100 microM V4+ concentration, the Vmax and K(m)
      values (for kemptide) are significantly less favourable than those obtained in
      the presence of 100 microM Mg2+. In summary, we have found that oxovanadium ions
      can directly alter the activity of the serine/threonine-specific PKA.

PMID- 9020862
TI  - Isolation and characterization of the androgen-dependent mouse cysteine-rich
      secretory protein-1 (CRISP-1) gene.
AB  - In mice, cysteine-rich secretory protein-1 (CRISP-1) is mainly found in the
      epididymis and also, to a lesser extent, in the salivary gland of males, where
      androgens control its expression. We have now isolated and characterized
      overlapping phage clones covering the entire length of the CRISP-1 gene. DNA
      sequencing revealed that the gene is organized into eight exons, ranging between
      55 and 748 bp in size, and seven introns. All exon-intron junctions conformed to
      the GT/AG rule established for eukaryotic genes. The intron length, as determined
      by PCR, varied between 1.05 and 4.0 kb so that the CRISP-1 gene spans over 20 kb
      of the mouse genome. The transcription-initiation site was determined by primer
      extension and localized at the expected distance downstream of a consensus TATA
      box. Approximately 3.7 kb of the CRISP-1 promoter region were isolated and
      sequenced, and several stretches fitting the androgen-responsive element
      consensus were found. Those that most resembled the consensus were analysed by
      electrophoretic mobility-shift assay and found to form specific complexes with
      the liganded androgen receptor in vitro, but with different affinities. Putative
      binding elements for the transcription factors Oct, GATA, PEA3, CF1. AP-1 and AP
      3 were also found in the promoter region.

PMID- 9020864
TI  - Decreased carbonic anhydrase III levels in the liver of the mouse mutant 'toxic
      milk' (tx) due to copper accumulation.
AB  - The mouse mutant 'toxic milk' (tx) is characterized by marked hepatic
      accumulation of copper, similar to that found in patients with the genetic
      disorder of copper transport, Wilson disease. In addition, lactating tx females
      produce copper-deficient milk. To characterize further the biochemical basis of
      this defect, Western blots of tissue extracts from normal and tx mice were probed
      with various heavy-metal radioisotopes (63Ni. 65Zn and 64Cu). A 30 kDa Ni/Zn
      binding polypeptide was found to be markedly decreased in the livers of the tx
      mice. This protein was isolated from normal adult mice using a procedure based on
      Ni-chelation chromatography. The amino acid sequences of two CNBr peptides were
      identical with portions of the mouse skeletal muscle carbonic anhydrase III
      (CAIII) sequence. Two other peptides sequenced had closely related sequences to
      that of CAIII, but with two differences in 45 amino acids. These two peptides may
      be derived from a novel CAIII isoform, which we term CAIIIB to distinguish it
      from the published form, CAIIIA. We isolated a cDNA clone corresponding to CAIIIA
      and used this to show that CAIIIA mRNA was also decreased in the mutant liver,
      but not in muscle. Copper loading of normal mice also decreased hepatic CAIIIA
      mRNA, suggesting that the decrease in CAIII mRNA in the tx mouse liver is a
      secondary consequence of the high copper levels in the liver.

PMID- 9020865
TI  - Thiol oxidation by 2,2'-dithiodipyridine causes a reversible increase in
      cytoplasmic free Ca2+ concentration in pancreatic beta-cells. Role for inositol
      1,4,5-trisphosphate-sensitive Ca2+ stores.
AB  - 2,2'-Dithiodipyridine (2,2'-DTDP), a reactive disulphide that mobilizes Ca2+ from
      ryanodine-sensitive Ca2+ stores in muscle, induced a biphasic increase in
      cytoplasmic free Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells loaded
      with fura 2. This increase consisted of an early transient followed by a second,
      slower, rise. The [Ca2+]i transient was dependent on extracellular Ca2+ and
      disappeared on treatment with nimodipine. The reactive disulphide caused plasma
      membrane depolarization, as studied by the perforated-patch configuration of the
      patch-clamp technique. Hence membrane depolarization and opening of the L-type
      voltage-gated Ca2+ channels were responsible for the first transient in [Ca2+]i.
      The second slower increase in [Ca2+]i was prolonged but readily reversed by the
      disulphide-reducing agent 1,4-dithiothreitol. This increase in [Ca2+]i was not
      decreased by nimodipine or by omission of extracellular Ca2+, but was eliminated
      when the Ins(1,4,5)P3-sensitive Ca2+ pool was first depleted by carbachol.
      Ryanodine or its beta-alanyl analogue did not release Ca2+ from intracellular
      stores, and a high concentration of ryanodine did not inhibit Ca2+ release by
      2,2'-DTDP. The disulphide compound suppressed glucose metabolism and decreased
      the mitochondrial inner-membrane potential. We conclude that thiol oxidation by
      2,2'-DTDP affects Ca2+ homeostasis in beta-cells by multiple mechanisms. However,
      unlike the situation in muscle, in beta-cells 2,2'-DTDP releases Ca2+ from
      intracellular pools by mechanisms that do not involve activation of ryanodine
      receptors. Instead, in these cells the Ins(1,4,5)P3-sensitive intracellular Ca2+
      store comprises an alternative target for the Ca(2+)-mobilizing action of the
      reactive disulphide compound.

PMID- 9020866
TI  - Conformational changes in plant Ins(1,4,5)P3 receptor on interaction with
      different myo-inositol trisphosphates and its effect on Ca2+ release from
      microsomal fraction and liposomes.
AB  - The interaction of the only reported plant inositol trisphosphate receptor with
      different myo-inositol trisphosphates (InsP3 species), namely Ins(1,4,5)P3,
      Ins(1,3,4)P3, Ins(1,5,6)P3, and Ins(2,4,5)P3, were studied to assess the extent
      of Ca2+ mobilization from microsomes/vacuoles as well as liposomes in vitro.
      Ins(1,4,5)P3 and Ins(2,4,5)P3 bind with the receptor with comparable affinities,
      as evidenced from their dissociation constants (Kd approx. 100 nM at 5 degrees
      C), whereas the interaction between Ins(1,3,4)P3/Ins(1,5,6)P3 and the receptor
      was not detected even with these ligands at 5 microM. Ins(1,3,4)P3/Ins(1,5,6)P3
      isomers also do not elicit Ca2+ release from liposomes or microsomes/ vacuoles.
      The ability of any InsP3 to bind the receptor for Ins(1,4,5)P3 is a prime
      requirement for Ca2+ release. However, the comparison of binding affinities at a
      single temperature does not help to correlate it directly with the extent of Ca2+
      release from the intracellular stores because the concentration of Ca2+ released
      by Ins(1,4,5)P3 as estimated over a period of 20 s is 3500 +/- 200 nM/mg of
      protein and is about 4-fold higher than that by Ins(2,4,5)P3 under identical
      conditions. To understand the role of the receptor conformation in Ca2+ release
      by different isomers, we have probed the conformational change of the receptor
      when the different isomers bind to it. Accessibility of the tryptophan residues
      in the free and Ins(1,4,5)P3/Ins(2,4,5)P3-bound receptor was monitored by a
      neutral fluorescence quencher, acrylamide. The resulting Stern-Volmer-type
      quenching plots of the internal fluorescence indicate a change in the
      conformation of the receptor on binding to Ins(1,4,5)P3 and Ins(2,4,5)P3. It is
      also detected when far-UV CD spectra (205-250 nm) of the free and ligand
      [Ins(1,4,5)P3/Ins(2,4,5)P3]-bound receptor are compared. The results from CD
      spectroscopic studies further indicate that the conformational changes induced by
      the two isomers are different in nature. When thermodynamic parameters, such as
      enthalpy (delta H), entropy (delta S) and free energy (delta G), for the
      formation of the two InsP3-receptor complexes are compared, a major difference in
      the extent of changes in enthalpy and entropy is noted. All these findings taken
      together support the proposition that it is the overall interaction leading to
      the requisite conformational change in the receptor that determines the potency
      of the InsP3 isomers in their abilities of Ca2+ mobilization from the
      intracellular stores or reconstituted liposomes.

PMID- 9020867
TI  - Allosteric modulation of the activity of thrombin.
AB  - Substrates containing a P3 aspartic residue are in general cleaved poorly by
      thrombin. This may be partly due to an unfavourable interaction between the P3
      aspartate and Glu192 in the active site of thrombin. In Protein C activation and
      perhaps also thrombin receptor cleavage, binding of ligands at the anion-binding
      exosite of thrombin seems to improve the activity of thrombin with substrates
      containing a P3 aspartate. To investigate the importance of Glu192 and exosite
      binding in modulating thrombin's interactions with a P3 aspartate, peptidyl
      chloromethanes based on the sequence of the thrombin receptor (containing a P3
      aspartate) have been synthesized and the kinetics of their inactivation of alpha
      thrombin and the mutant Glu192-->Gln determined. The values of the inactivation
      rate constant (ki) for the chloromethanes containing a P3 aspartate were about
      two-fold higher with the Glu192-->Gln mutant. A peptide based on the sequence of
      hirudin (rhir52 65), which binds to the anion-binding exosite of thrombin, was an
      allosteric modulator of the amidolytic activity of the Glu192-->Gln mutant; a 5
      fold decrease in the K(m) value for the substrate D-Phe-pipecolyl-Arg-p
      nitroanilide was observed in the presence of saturating concentrations of rhir52
      65. This exosite-binding peptide also increased the ki values of chloromethanes
      containing a P3 aspartate with both alpha-thrombin and the Glu192-->Gln mutant.
      However, the increases in the ki values were greater with the Glu192-->Gln mutant
      (5-fold compared with 2-fold for alpha-thrombin). Thus exosite binding does not
      seem to mitigate putative unfavourable interactions between Glu192 and the P3
      aspartate. Moreover, increases in the ki caused by exosite binding were not
      unique to chloromethanes containing a P3 aspartate; increases of the same
      magnitude were also observed when the P3 position was occupied by the favourable
      D-phenylalanine in place of the unfavourable aspartate. The results obtained were
      consistent with exosite binding's causing changes in the conformation of the S2
      and/or S1 site of thrombin.

PMID- 9020868
TI  - Mutations within the propeptide, the primary cleavage site or the catalytic site,
      or deletion of C-terminal sequences, prevents secretion of proPC2 from
      transfected COS-7 cells.
AB  - PC2 is a neuroendocrine endoprotease involved in the processing of prohormones
      and proneuropeptides. PC2 is synthesized as a proenzyme which undergoes
      proteolytic maturation within the cellular secretory apparatus. Cleavage occurs
      at specific sites to remove the N-terminal propeptide. The aim of the present
      study was to investigate structural requirements for the transfer of proPC2
      through the secretory pathway. A series of mutant proPC2 constructs were
      transfected into COS-7 cells and the fate of the expressed proteins followed by
      pulse-chase analysis and immunocytochemistry. Human PC2 was secreted relatively
      slowly, and appeared in the medium primarily as proPC2 (75 kDa), together with
      much lower amounts of a processed intermediate (71 kDa) and mature PC2 (68 kDa).
      Mutations within the primary processing site or the catalytic triad caused the
      protein to accumulate intracellularly, whereas deletion of part of the
      propeptide, the P-domain or the C-terminal regions also prevented secretion.
      Immunocytochemistry showed that wild-type hPC2 was localized mainly in the Golgi,
      whereas two representative mutants showed a distribution typical of proteins
      resident in the endoplasmic reticulum. The results suggest that proenzyme
      processing is not essential for secretion of PC2, but peptides containing
      mutations that affect the ability of the propeptide (and cleavage sites) to fold
      within the catalytic pocket are not transferred beyond the early stages of the
      secretory pathway. C-terminal sequences may be involved in stabilizing such
      conformations.

PMID- 9020869
TI  - The beta-D-xylosidase of Trichoderma reesei is a multifunctional beta-D-xylan
      xylohydrolase.
AB  - An extracellular multifunctional beta-D-xylan xylohydrolase, previously described
      as beta-xylosidase, was purified from Trichoderma reesei RUT C-30 to physical
      homogeneity. The active enzyme was a 100 (+/-5) kDa glycosylated monomer that
      exhibited a pl of 4.7. Its activity was optimal at pH 4 and it was stable between
      pH 3 and 6. Its temperature-stability was moderate (70 degrees zero of activity
      remaining after 60 min at 50 degrees C) and optimal activity was observed at 60
      degrees C. It is capable of hydrolysing beta-1.4-xylo-oligosaccharides [degree of
      polymerization (DP) 2-7], the apparent Vmax increasing with increasing chain
      length. The enzyme also attacked debranched beech-wood (Lenzing) xylan and 4-O
      methylglucuronoxylan, forming xylose as the only end product. The K(m) for xylan
      was 0.7 g/l. For this reason we consider the enzyme to be a beta-D-xylan
      xylohydrolase. The enzyme also exhibits alpha-L-arabinofuranosidase activity on 4
      nitrophenyl alpha-L-arabinofuranoside, and evidence is presented that this is not
      caused by an impurity in the enzyme preparation. The beta-D-xylan xylohydrolase
      exhibits glycosyltransferase activity with xylo-oligosaccharides and at high
      concentrations of 4-nitrophenyl beta-D-xylopyranoside (4-Nph-beta-Xyl). The
      enzyme hydrolyses beta-1, 4-linkages preferentially to beta-1,3-linkages, and
      beta-1,2-linked xylo-oligosaccharides are not hydrolysed at all. The enzyme
      liberates terminal beta-1,4-xylopyranose residues linked to a 2-O-substituted
      xylopyranose residue, but not that linked to a 3-O-substituted xylopyranose
      residue. The enzyme does not attack methyl, methyl 1-thio-benzyl or butyl l-thio
      beta-D-xylopyranosides and 4-naphthyl, 2-naphthyl and phenyl beta-D
      xylopyranosides.

PMID- 9020870
TI  - Regulation of the thyroid NADPH-dependent H2O2 generator by Ca2+: studies with
      phenylarsine oxide in thyroid plasma membrane.
AB  - Pig thyroid plasma membranes contain a Ca(2+)-dependent NADPH:O2 oxidoreductase,
      the thyroid NADPH-dependent H2O2 generator. This provided the H2O2 for the
      peroxidase-catalysed synthesis of thyroid hormones. The effect of the tervalent
      arsenical, phenylarsine oxide (PAO), on the NADPH oxidase was studied. PAO caused
      two directly related dose-dependent effects with similar half-effect
      concentrations of PAO (3 nmol of PAO/mg of protein): (i) partial inactivation of
      H2O2 formation by the Ca(2+)-stimulated enzyme, and (ii) desensitization of the
      enzyme activity to Ca2+. PAO had no effect on membranes that had been Ca(2+)
      desensitized by alpha-chymotrypsin treatment. The NADPH oxidase in membranes
      treated with excess PAO had the same Vmax with and without Ca2+. This value was
      half the Vmax of the native enzyme. However, the K(m) for NADPH determined with
      Ca2+ (18 microM, identical with that of the native enzyme) was approx, one-third
      of the K(m) measured without Ca2+, showing the direct action of Ca2+ on the PAO
      enzyme complex. PAO had the same effects, partial inactivation and Ca2+
      desensitization, on the NADPH: ferricyanide oxidoreductase activity of the NADPH
      oxidase, suggesting that PAO acts on the flavodehydrogenase entity of the enzyme.
      Both partial inactivation and Ca2+ desensitization were completely and
      specifically reversed by 2.3-dimercaptopropanol, partly reversed by
      dithiothreitol and not reversed by 2-mercaptoethanol, indicating that PAO binds
      to vicinal thiol groups. These results suggest that thiol groups are involved in
      the control of thyroid NADPH oxidase by Ca2+; PAO bound to vicinal thiols might
      alter the structure of the enzyme so that electron transfer occurs without Ca2+
      but more slowly.

PMID- 9020871
TI  - Regulation of mdr2 P-glycoprotein expression by bile salts.
AB  - The phosphatidyl translocating activity of the mdr2 P-glycoprotein (Pgp) in the
      canalicular membrane of the mouse hepatocyte is a rate-controlling step in the
      biliary secretion of phospholipid. Since bile salts also regulate the secretion
      of biliary lipids, we investigated the influence of the type of bile salt in the
      circulation on mdr2 Pgp expression and activity. Male mice were led a purified
      diet to which either 0.1% (w/w) cholate or 0.5% (w/w) ursodeoxycholate was added.
      This led to a near-complete replacement of the endogenous bile salt pool (mainly
      tauromuricholate) by taurocholate or tauroursodeoxycholate respectively. The
      phospholipid secretion capacity was then determined by infusion of increasing
      amounts of tauroursodeoxycholate. Cholate feeding resulted in a 55% increase in
      maximal phospholipid secretion compared with that in mice on the control diet.
      Northern blotting revealed that cholate feeding increased mdr2 Pgp mRNA levels by
      42%. Feeding with ursodeoxycholate did not influence the maximum rate of
      phospholipid output or the mdr2 mRNA content. Female mice had a higher basal mdr2
      Pgp mRNA level than male mice, and this was also correlated with a higher
      phospholipid secretion capacity. This could be explained by the 4-fold higher
      basal cholate content in the bile of female compared with male mice. Our results
      suggest that the type of bile salts in the circulation influences the expression
      of the mdr2 gene.

PMID- 9020872
TI  - The YNT1 gene encoding the nitrate transporter in the yeast Hansenula polymorpha
      is clustered with genes YNI1 and YNR1 encoding nitrite reductase and nitrate
      reductase, and its disruption causes inability to grow in nitrate.
AB  - DNA sequencing in the phage lambda JA13 isolated from a lambda EMBL3 Hansenula
      polymorpha genomic DNA library containing the nitrate reductase-(YNR1) and
      nitrite reductase-(YNI1) encoding genes revealed an open reading frame (YNT1) of
      1524 nucleotides encoding a putative protein of 508 amino acids with great
      similarity to the nitrate transporters from Aspergillus nidulans and
      Chlamydomonas reinhardtii. Disruption of the chromosomal YNT1 copy resulted in
      incapacity to grow in nitrate and a significant reduction in rate of nitrate
      uptake. The disrupted strain is still sensitive to chlorate, and, in the presence
      of 0.1 mM nitrate, the expression of YNR1 and YNI1 and the activity of nitrate
      reductase and nitrite reductase are significantly reduced compared with the wild
      type. Northern-blot analysis showed that YNT1 is expressed when the yeast is
      grown in nitrate and nitrite but not in ammonium solution.

PMID- 9020873
TI  - Structure and expression of a cluster of glutathione S-transferase genes from a
      marine fish, the plaice (Pleuronectes platessa).
AB  - Glutathione S-transferases are involved in the detoxification of reactive
      electrophilic compounds, including intracellular metabolites, drugs, pollutants
      and pesticides. A cluster of three glutathione S-transferase genes, designated
      GSTA, GSTA1 and GSTA2, was isolated from the marine flatfish, plaice
      (Pleuronectes platessa). GSTA and GSTA1 code for protein products with 76% amino
      acid identity. GSTA2 appears to contain a single nucleotide deletion which would
      render any product non-functional. All of these genes consist of six exons of
      similar sizes and greater than 70% nucleotide identity, and are interrupted by
      five introns of differing sizes. GSTA and GSTA1 mRNAs were present in a range of
      tissues, while GSTA2 mRNA was no detected. Expression of GSTA mRNA was increased
      in plaice intestine and spleen by pretreatment with beta-naphthoflavone, and
      expression of both GSTA and GSTA1 mRNAs was increased in plaice liver and gill by
      pretreatment with the peroxisome proliferating agent perfluoro-octanoic acid.

PMID- 9020874
TI  - Kinetic and thermodynamic consequences of the removal of the Cys-77-Cys-123
      disulphide bond for the folding of TEM-1 beta-lactamase.
AB  - Class A beta-lactamases of the TEM family contain a single disulphide bond which
      connects cysteine residues 77 and 123. To clarify the possible role of the
      disulphide bond in the stability and folding kinetics of the TEM-1 beta
      lactamase, this bond was removed by introducing a Cys-77-->Ser mutation, and the
      enzymically active mutant protein was studied by reversible guanidine
      hydrochloride-induced denaturation. The unfolding and refolding rates were
      monitored using tryptophan fluorescence. At low guanidine hydrochloride
      concentrations, the refolding of the wild-type and mutant enzymes followed
      biphasic time courses. The characteristics of the two phases were not
      significantly affected by the mutation. Double-jump experiments, in which the
      protein was unfolded in a high concentration of guanidine hydrochloride for a
      short time period and then refolded by diluting out the denaturant, indicated
      that, for both the wild-type and mutant enzymes, the two refolding phases could
      be ascribed to proline isomerization reactions. Equilibrium unfolding experiments
      monitored by fluorescence spectroscopy and far-UV CD indicated a three-state
      mechanism (N<-->H<--U). Both the folded mutant protein (N) and, to a lesser
      extent the thermodynamically stable intermediate, H. were destabilized relative
      to the fully unfolded state, U. Removal of the disulphide bond resulted in a
      decrease of 14.2 kJ/mol (3.4 kcal/mol) in the global free energy of
      stabilization. Similarly, the mutation also induced a drastic increase in the
      rate of thermal inactivation.

PMID- 9020875
TI  - Glycosylation is essential for biosynthesis of functional gastric H+,K+-ATPase in
      insect cells.
AB  - The role of N-linked glycosylation in the functional properties of gastric H+,K+
      ATPase has been examined with tunicamycin and I-deoxymannojirimycin, inhibitors
      in glycoprotein biosynthesis and glycoprotein processing respectively.
      Tunicamycin completely abolished both K+-stimulated and 3-(cyanomethyl)-2-methyl
      8-(phenylmethoxy)-imidazo[1,2a]pyridine (SCH 28080)-sensitive ATPase activity and
      SCH 28080-sensitive phosphorylation capacity. The expression level of both H+,K+
      ATPase subunits remained unaffected. 1-Deoxymannojirimycin clearly affected the
      structure of the N-linked oligosaccharide moieties without affecting specific
      phosphorylation capacity. Purification of the functional recombinant enzyme from
      non-functional H+,K+-ATPase subunits coincided with purification of glycosylated
      beta-subunits and not of non-glycosylated beta-subunits. Transport of the H+,K+
      ATPase beta-subunit to the plasma membrane but not its ability to assemble with
      the alpha-subunit dependent on N-glycosylation events. We conclude that the
      acquisition, but not the exact structure, of N-linked oligosaccharide moieties,
      is essential for biosynthesis of functional gastric H+,K+-ATPase in insect cells.

PMID- 9020876
TI  - Hepatic lipase is localized at the parenchymal cell microvilli in rat liver.
AB  - Hepatic lipase (HL) is thought to be located at the vascular endothelium in the
      liver. However, it has also been implicated in the binding and internalization of
      chylomicron remnants in the parenchymal cells. In view of this apparent
      discrepancy between localization and function, we re-investigated the
      localization of HL in rat liver using biochemical and immunohistochemical
      techniques. The binding of HL to endothelial cells was studied in primary
      cultures of rat liver endothelial cells. Endothelial cells bound HL in a
      saturable manner with high affinity. However, the binding capacity accounted for
      at most 1% of the total HL activity present in the whole liver. These results
      contrasted with earlier studies, in which non-parenchymal cell (NPC) preparations
      had been found to bind HL with a high capacity. To study HL binding to the
      different components of the NPC preparations, we separated endothelial cells,
      Kupffer cells and blebs by counterflow elutriation. Kupffer cells and endothelial
      cells showed a relatively low HL-binding capacity. In contrast, the blebs,
      representing parenchymal-cell-derived material, had a high HL-binding capacity
      (33 m-units/mg of protein) and accounted for more than 80% of the total HL
      binding in the NPC preparation. In contrast with endothelial and Kupffer cells,
      the HL-binding capacity of parenchymal cells could account for almost all the HL
      activity found in the whole liver. These data strongly suggest that HL binding
      occurs at parenchymal liver cells. To confirm this conclusion in situ, we studied
      HL localization by immunocytochemical techniques. Using immunofluorescence, we
      confirmed the sinusoidal localization of HL. Immunoelectron microscopy
      demonstrated that virtually all HL was located at the microvilli of parenchymal
      liver cells, with a minor amount at the endothelium. We conclude that, in rat
      liver, HL is localized at the microvilli of parenchymal cells.

PMID- 9020877
TI  - P52PAI-1 gene expression in butyrate-induced flat revertants of v-ras-transformed
      rat kidney cells: mechanism of induction and involvement in the morphological
      response.
AB  - Sodium n-butyrate-induced flat reversion in v-K-ras oncogene-transformed rat
      kidney (KNRK) cells is associated with transcriptional activation of the p52PAI-1
      gene (which encodes the type-1 inhibitor of plasminogen activator). Butyrate
      initiated expression of p52PAI-1 mRNA and protein correlated with induced cell
      spreading and preceded development of cell-to-substrate focal adhesions. Such
      undersurface matrix contact structures, which are absent from parental KNRK
      cells, require proximal PAI-1 deposition for their stabilization. Stimulated
      p52PAI-1 expression by flat revertants (approximating 25-fold that of control
      cells) and the accompanying cytoarchitectural reorganization appeared to be
      programmed responses to butyrate as both events required de novo RNA and protein
      synthesis, metabolic characteristics consistent with a secondary pathway of gene
      regulation. To assess the relevance of p52PAI-1 induction to the process of flat
      reversion more critically, a molecular genetic approach was designed to maintain
      high-level constitutive p52PAI-1 synthesis in the absence of butyrate. KNRK cells
      transfected with a Rc/CMVPAI plasmid construct, in which expression of a p52PAI-1
      cDNA insert was driven by enhancer-promoter sequences from the immediate-early
      gene of human cytomegalovirus, formed colonies comprised of flat-revertant-like
      cells with a greater frequency than did cells transfected with the Rc/CMV vector
      alone (24.8% and 1.7% respectively). Comparative analysis of randomly selected
      Rc/ CMVPAI clones indicated that a 10-fold increase in immunoreactive p52PAI-1
      protein, relative to Rc/CMV isolates, correlated with generation of the flat
      phenotype. These data suggest that induced p52PAI-1 expression probably functions
      in the development of morphological revertants in the KNRK cell system.

PMID- 9020878
TI  - Neuropeptide Y modulates ATP-induced increases in internal calcium via the
      adenylate cyclase/protein kinase A system in a human neuroblastoma cell line.
AB  - The modulatory effects of neuropeptide Y (NPY) on ATP-induced increases in
      cytosolic free-calcium concentration ([Ca2+]i) were investigated in the CHP-234
      human neuroblastoma cell line. Pretreatment of cells with 100 nM NPY potentiated
      the increase in [Ca2+]i evoked subsequently by 20 microM ATP, compared with
      initial application of ATP in a control experiment, whereas a similar
      pretreatment with 1 microM NPY attenuated the subsequent response to ATP. Both
      actions of NPY were completely blocked by H-89 [N-[2-((3-(4-bromo-phenyl)-2
      propenyl)-amino)-ethyl]-5 isoquinoline sulphonamide dihydrochloride], a selective
      antagonist of protein kinase A. The effects of 100 nM NPY were mimicked by H-89,
      while forskolin and 8-Br-cAMP mimicked the effects of 1 microM NPY. Both basal
      and forskolin-stimulated cAMP levels were inhibited by 100 nM NPY and by 100 nM
      NPY(13-36), a selective agonist of the NPY Y2-receptor subtype. In contrast, at 1
      microM such inhibition was not observed for either NPY or NPY(13-36). It is
      concluded that NPY has a biphasic modulatory effect on increases in [Ca2+]i
      produced by ATP, which probably involves the cAMP/protein kinase A cascade.

PMID- 9020879
TI  - Reduced very-low-density lipoprotein fractional catabolic rate in apolipoprotein
      C1-deficient mice.
AB  - The function of apolipoprotein (apo) C1 in vivo is not clearly defined. Because
      transgenic mice overexpressing human apoC1 show elevated triacylglycerol (TG)
      levels [Simonet, Bucay, Pitas, Lauer and Taylor (1991) J. Biol. Chem. 266, 8651
      8654], an as yet unknown role for apoC1 in TG metabolism has been suggested. Here
      we investigated directly the effect of the complete absence of apoC1 on very-low
      density lipoprotein (VLDL)-TG lipolysis, clearance and production, by performing
      studies with the previously generated apoC1-deficient mice. On a sucrose-rich,
      low fat/low cholesterol (LFC) diet, apoC1-deficient mice accumulate in their
      circulation VLDL particles, which contain relatively lower amounts of lipids when
      compared with VLDL isolated from control mice. Lipolysis assays in vitro on VLDL
      from apoC1-deficient and control mice showed no differences in apparent K(m) and
      Vmax values (0.27 +/- 0.06 versus 0.24 +/- 0.03 mmol of TG/litre and 0.40 +/-
      0.03 versus 0.36 +/- 0.03 mmol of non-esterified fatty acid (NEFA)/min per litre
      respectively). To correct for potential differences in the size of the VLDL
      particles, the resulting K(m) values were also expressed relative to apoB
      concentration. Under these conditions apoC1-deficient VLDL displayed a lower, but
      not significant, K(m) value when compared with control VLDL (3.44 +/- 0.71 versus
      4.44 +/- 0.52 mmol of TG2/g apoB per litre). VLDL turnover studies with
      autologous injections of [3H]TG-VLDL in vivo showed that the VLDL fractional
      catabolic rate (FCR) was decreased by up to 50% in the apoC1-deficient mice when
      compared with control mice (10.5 +/- 3.4 versus 21.0 +/- 1.2/h of pool TG). No
      significant differences between apoC1-deficient and control mice were observed in
      the hepatic VLDL production estimated by Triton WR139 injections (0.19 +/- 0.02
      versus 0.21 +/- 0.05 mmol/h of TG per kg) and in the extra-hepatic lipolysis of
      VLDL-TG (4.99 +/- 1.62 versus 3.46 +/- 1.52/h of pool TG) in vivo. Furthermore,
      [125I]VLDL-apoB turnover experiments in vivo also showed a 50% decrease in the
      FCR of VLDL in apoC1-deficient mice when compared with control mice on the LFC
      diet (1.1 +/- 0.3 versus 2.1 +/- 0.1/h of pool apoB). When mice were fed a very
      high fat/high cholesterol (HFC) diet, the VLDL-apoB FCR was further decreased in
      apoC1-deficient mice (0.4 +/- 0.1 versus 1.4 +/- 0.4/h of pool apoB). We conclude
      that, in apoC1-deficient mice, the FCR of VLDL is reduced because of impaired
      uptake of VLDL remnants by hepatic receptors, whereas the production and
      lipolysis of VLDL-TG is not affected.

PMID- 9020880
TI  - Developmental and nutritional changes of ob and PPAR gamma 2 gene expression in
      rat white adipose tissue.
AB  - The ob gene encodes leptin, a hormone which induces satiety and increases energy
      expenditure. The peroxisome proliferator-activated receptor gamma 2 isoform (PPAR
      gamma 2) gene encodes a transcription factor which controls adipocyte
      differentiation and expression of fat-specific genes. We have studied the
      regulation of these two genes in white adipose tissue (WAT) during the suckling
      weaning transition. Suckling rats ingest a high-fat diet (milk). Fat-pad weight
      barely varied during the last week of suckling. ob mRNA levels, which were very
      low in 15-day-old rats, rose approximately 6-fold until weaning at 21 days. When
      the rats were weaned on to a standard (high-carbohydrate) laboratory chow,
      epididymal WAT enlarged approximately 7-fold, and ob mRNA kept increasing
      progressively and doubled between 21 and 30 days. This evolution contrasted with
      that of fatty acid synthase (FAS) mRNA, which increased sharply, but only after
      weaning. To distinguish between the influence of developmental and nutritional
      factors on ob expression, a group of rats was weaned on to a high-fat diet. This
      prevented the rise in glycaemia and insulinaemia and the decrease in plasma non
      esterified fatty acids which otherwise occurred at weaning. This also resulted in
      a slight (10-15%) decrease in food intake and body weight gain. Under this high
      fat diet, the rise of ob mRNA in WAT was augmented (3.7-fold in 30- versus 21-day
      old pups), whereas the normal rise in FAS mRNA levels was attenuated. Fat-pad
      weights and adipocyte cell size and number were roughly similar in high
      carbohydrate- and high-fat-weaned pups. mRNA levels of PPAR gamma 2, like those
      of ob, were low in the WAT of 15-day-old suckling pups, doubled at 21 days, and
      reached a maximum as soon as 23 days. This evolution further differed from that
      of ob mRNA in not being influenced by diet composition. In conclusion, ob
      expression markedly increases during the suckling-weaning transition, and this
      effect is accentuated by a high-fat diet. Qualitative nutritional changes in ob
      mRNA were correlated with neither acute changes in adipose-tissue mass, nor cell
      size/number, nor variations in insulinaemia. PPAR gamma 2 also increased during
      suckling, but rapidly reached a plateau after weaning and no longer changed
      thereafter. Unlike ob, PPAR gamma 2 was not influenced by the diet composition.

PMID- 9020881
TI  - Characterization of a partially structured state in an all-beta-sheet protein.
AB  - Cardiotoxin analogue III (CTX III) is a low-molecular-mass all-beta-sheet protein
      isolated from the Taiwan cobra (Naja naja atra) venom. A stable partially
      structured state similar to the "molten globule' state has been identified for
      CTX III in a 3% (w/v) solution of 2,2,2-trichloroacetic acid at 298 K. This
      stable state has been structurally characterized using a variety of techniques
      such as CD, 1-anilinonaphthalene-8-sulphonate fluorescence binding, Fourier
      transform IR and two-dimensional NMR spectroscopy techniques. Direct assignment
      of the homonuclear two-dimensional NMR spectra of the protein in 3%
      trichloroacetic acid showed that drastic structural perturbation had not taken
      place in the protein and that the 'intermediate' state retained a significant
      portion of the native secondary-structural interactions. It is found that about
      65% of the native beta-sheet structural contacts are maintained in the partially
      structured state of CTX III in 3% trichloroacetic acid.

PMID- 9020882
TI  - Organization of the human beta-1,2-N-acetylglucosaminyltransferase I gene
      (MGAT1), which controls complex and hybrid N-glycan synthesis.
AB  - UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (EC
      2.4.1.101; GlcNAc-T I) is a medial-Golgi enzyme which catalyses the first step in
      the conversion of oligomannose-type to N-acetyl-lactosamine- and hybrid-type N
      glycans and is essential for normal embryogenesis in the mouse. Previous work
      indicated the presence of at least two exons in the human GlcNAc-T I gene MGAT1,
      exon 2 containing part of the 5' untranslated region and the complete coding and
      3' untranslated regions, and exon 1 with the remainder of the 5' untranslated
      region. We now report the cloning and sequencing of a human genomic DNA fragment
      containing exon 1, which is between 5.6 and 15 kb upstream of exon 2. Transient
      transfection, ribonuclease protection and reverse transcriptase-mediated PCR
      indicated the absence of transcription start sites in intron 1 between exons 1
      and 2. Northern analysis, ribonuclease protection, primer extension analysis and
      rapid amplification of 5'-cDNA ends showed that there are multiple transcription
      start sites for exon 1 compatible with the expression by several human cell lines
      and tissues of two transcripts, a broad band ranging in size from 2.7 to 3.0 kb
      and a sharper band at 3.1 kb. The 5' flanking region of exon 1 has a GC content
      of 81% and has no canonical TATA or CCAAT boxes but contains potential binding
      sites for transcription factors Sp1, GC-binding factor and epidermal growth
      factor receptor-specific transcription factor. Chloramphenicol acetyltransferase
      (CAT) expression was observed on transient transfection into HeLa cells of a
      fusion construct containing the gene for CAT and a genomic DNA fragment from the
      5' flanking region of exon 1. It is concluded that MGAT1 is a typical
      housekeeping gene although there is, in addition, tissue-specific expression of
      the larger 3.1 kb transcript.

PMID- 9020883
TI  - Effect of pH on kinetic parameters of NAD+-dependent formate dehydrogenase.
AB  - To define in detail the molecular mechanism of NAD+-dependent formate
      dehydrogenase, the pH dependences of various kinetic and spectroscopic parameters
      have been studied: Vmax, Km (NAD+), Km (formate), inhibition constants for
      structural analogues of substrate (NO3-) and product (CNS-, CNO-, N3-), CD and
      fluorescence properties. The value of Vmax, rate-limiting hydride transfer, is
      nearly constant throughout the entire pH range of enzyme stability (6.0-11.2) but
      decreases below 6. The K(m) values for both substrates remain constant within the
      pH range 6-10. At pH values below 6 (for the coenzyme) and above 10 (for both
      substrate and coenzyme) the Km values increase. In the acidic range this change
      is attributed to the ionization of two carboxy groups (pK approx. 5.5-6.0)
      located at the NAD+-binding site of the enzyme active centre. The pH transition
      in the basic region (pK 10.5 +/- 0.2) has a conformational origin and affects the
      enzyme's affinity for substrates and anion inhibitors. A similar transition has
      been observed for formate dehydrogenases from yeast Candida boidinii and
      Hansenula polymorpha. The results complement the conclusions about the catalytic
      mechanism deduced from the crystal structure of the enzyme.

PMID- 9020884
TI  - The dependence of DNase I activity on the conformation of oligodeoxynucleotides.
AB  - We have developed a sensitive continuous assay for nucleases using proton
      release. The assay has been applied to the determination of the kinetics of DNase
      I acting on short, defined deoxyoligonucleotides. The dependence of Kcat/K(m) on
      sequence and structure of short oligonucleotide substrates has been measured:
      increasing lengths of AnTn sequences decrease the rate of cleavage. G.A
      mismatches in which the bases pair using imino protons are cleaved quite
      effectively by DNase I. In contrast, tandem G.A mismatches which use amino
      pairing and have BII phosphodiesters, are refractory to DNase I. Also, the DNA
      strands of DNA.RNA hybrid duplexes are not cleaved by DNase I. These results show
      that the global conformation of a duplex and the details of its minor groove
      affect the cleavage efficiency by DNase I. The assay has also been used to
      measure the inhibition constant of the minor-groove-binding ligand propamidine. A
      value of 3 microM has been determined for binding to the sequence
      d(CGCGAATTCGCG)2, showing that dissociation constants can be determined even when
      there are no convenient optical signals for titrations.

PMID- 9020885
TI  - Mechanism of glucose and maltose transport in plasma-membrane vesicles from the
      yeast Candida utilis.
AB  - Transport of glucose and maltose was studied in plasma-membrane vesicles from
      Candida utilis. The yeast was grown on a mixture of glucose and maltose in
      aerobic carbon-limited continuous cultures which enabled transport to be studied
      for both sugars with the same vesicles. Vesicles were prepared by fusion of
      isolated plasma membranes with proteoliposomes containing bovine heart cytochrome
      c oxidase as a proton-motive-force-generating system. Addition of reduced
      cytochrome c generated a proton-motive force, consisting of a membrane potential,
      negative inside, and a pH gradient, alkaline inside. Energization led to
      accumulation of glucose and maltose in these vesicles, reaching accumulation
      ratios of about 40-50. Accumulation also occurred in the presence of valinomycin
      or nigericin, but was prevented by a combination of the two ionophores or by
      uncoupler, showing that glucose and maltose transport are dependent on the proton
      motive force. Comparison of sugar accumulation with quantitative data on the
      proton-motive force indicated a 1:1 H+/sugar stoichiometry for both transport
      systems. Efflux of accumulated glucose was observed on dissipation of the proton
      motive force. Exchange and counterflow experiments confirmed the reversible
      character of the H+-glucose symporter. In contrast, uncoupler or a mixture of
      valinomycin plus nigericin induced only a slow efflux of accumulated maltose.
      Moreover under counterflow conditions, the expected transient accumulation was
      small. Thus the H+-maltose symporter has some characteristics of a carrier that
      is not readily reversible. It is concluded that in C. utilis the transport
      systems for glucose and maltose are both driven by the proton-motive force, but
      the mechanisms are different.

PMID- 9020886
TI  - Interleukin 1-beta-induced protein kinase C-zeta activation is mimicked by
      exogenous phospholipase D.
AB  - Interleukin 1-beta (IL1-beta) is a pleiotropic cytokine that stimulates a number
      of signal transduction pathways in cells, leading to different cellular
      responses. In this study we investigated the signal transduction pathways
      activated by IL1-beta in two different human cell lines: RD/TE671, a
      rhabdomyosarcoma, and EJ, a bladder-derived carcinoma. We showed that this
      cytokine induced the activation of protein kinase C-zeta (PKC-zeta) and the
      accumulation of a putative physiological PKC-zeta activator, phosphatidic acid
      [Limatola, Schaap, Moolenaar and van Blitterswijk (1994) Biochem. J. 304, 1001
      1008]. Exogenously supplied phospholipase D, which generated cellular
      phosphatidic acid, was able to mimic the cytokine effect, supporting the
      hypothesis that this lipid second messenger might contribute to cytokine-induced
      PKC-zeta activation. In addition, we show that IL1-beta stimulation of BOSC23
      cells, transiently overexpressing PKC-zeta, induced an increase in PKC-zeta
      autophosphorylation. These results give the first direct evidence that IL1-beta
      can activate this atypical PKC isoform and suggest that this enzyme might be
      involved in mediating some of the biological effects induced by IL1-beta.

PMID- 9020887
TI  - Mechanism of inactivation of myeloperoxidase by 4-aminobenzoic acid hydrazide.
AB  - Hypochlorous acid is the most powerful oxidant generated by neutrophils and is
      likely to contribute to the damage mediated by these inflammatory cells. The haem
      enzyme myeloperoxidase catalyses its production from hydrogen peroxide and
      chloride. 4-Aminobenzoic acid hydrazide (ABAH) is a potent inhibitor of
      hypochlorous acid production. In this investigation we show that, in the presence
      of hydrogen peroxide, ABAH irreversibly inactivates myeloperoxidase. ABAH was
      oxidized by myeloperoxidase, and kinetic analysis of the inactivation conformed
      to that for a mechanism-based inhibitor. Inactivation was exacerbated by
      concentrations of hydrogen peroxide greater than 50 microM and by the absence of
      oxygen. Hydrogen peroxide alone caused minimal inactivation. Reduced glutathione
      inhibited the oxidation of ABAH as well as the irreversible inhibition of
      myeloperoxidase. In the presence of oxygen, ABAH and hydrogen peroxide initially
      converted myeloperoxidase into compound III, which subsequently lost haem
      absorbance. In the absence of oxygen, the enzyme was converted into ferrous
      myeloperoxidase and its haem groups were rapidly destroyed. We propose that
      myeloperoxidase oxidizes ABAH to a radical that reduces the enzyme to its ferrous
      intermediate. Ferrous myeloperoxidase reacts either with oxygen to allow enzyme
      turnover, or with hydrogen peroxide to give irreversible inactivation.

PMID- 9020888
TI  - Polymorphism and structure of the gene coding for the alpha 1 subunit of the
      Artemia franciscana Na/K-ATPase.
AB  - Genomic clones coding for one of the two identified Artemia franciscana Na/K
      ATPase alpha subunits, the alpha 1 subunit, have been isolated. Several
      overlapping clones were obtained, although their restriction maps showed a large
      heterogeneity. Sequencing of their exons showed that they differ in up to 3.46%
      of their nucleotides in translated regions and 8.18% in untranslated regions.
      Southern blot analysis of DNA purified from different lots of A. franciscana
      cysts and from isolated individuals suggests that the variation is due to the
      existence of multiple Na/K-ATPase alpha 1 subunit alleles in A. franciscana. The
      Na/K-ATPase alpha 1 subunit gene is divided into 15 exons. Ten of the 14 introns
      are located in identical positions in this gene as in the human Na/K-ATPase alpha
      3 subunit gene. Analysis of the 5' flanking region of the gene has allowed
      identification of the transcription-initiation sites. The adjacent upstream
      region has been shown to have functional promoter activity in cultured mammalian
      cells, suggesting the evolutionary conservation of some of the promoter
      regulatory sequences.

PMID- 9020889
TI  - Correlation between calponin and myosin subfragment 1 binding to F-actin and
      ATPase inhibition.
AB  - Calponin is a thin-filament-associated protein that has been implicated in the
      regulation of smooth-muscle contractility. It binds to F-actin and inhibits the
      MgATPase activity of actomyosin. In the present work we have examined the effect
      of recombinant chicken gizzard alpha-calponin (R alpha CaP) on the binding of
      rabbit skeletal-muscle myosin subfragment 1 (S1) to F-actin and on the inhibition
      of its actin-activated MgATPase. We have found that binding of one R alpha CaP
      molecule to every three to four actin monomers is sufficient for maximal
      inhibition of acto-S1 ATPase. At this R alpha CaP/actin ratio R alpha CaP does
      not interfere with S1 binding to F-actin. At higher concentrations, R alpha CaP
      displaces S1 from F-actin and a 1:1 R alpha CaP-actin monomer complex is formed.
      R alpha CaP is also able to displace troponin I from its complex with F-actin
      which may reflect the amino acid sequence similarity between R alpha CaP and
      troponin I in their actin-binding regions.

PMID- 9020890
TI  - Ras activation in platelets after stimulation of the thrombin receptor,
      thromboxane A2 receptor or protein kinase C.
AB  - Several reports have indicated that the small G-protein Ras is not present
      immunologically in platelets. However, here we report the identification of Ras
      in platelets by immunoprecipitation with the Ras-specific monoclonal antibodies
      Y13-259 or Y13-238, followed by Western blotting. The presence of Ras was not due
      to contamination of samples with erythrocytes or leucocytes. Immunofluorescence
      studies indicated that Ras was present in a peripheral rim pattern in fixed,
      permeabilized platelets, suggesting an intracellular, plasma membrane location.
      Activation of platelets with the thrombin receptor peptide42-50, the
      prostaglandin H2/thromboxane A2 mimetic U46619 or phorbol 12-myristate 13-acetate
      induced a rapid increase in GTP-bound, activated Ras. In each case, this increase
      was inhibited by the protein kinase C (PKC) inhibitor bisindolylmaleimide GF
      109203X, suggesting that Ras is activated downstream of PKC in platelets. Thus
      the activation of Ras in platelets by agonists will now allow consideration of
      multiple potential Ras-dependent signal transduction pathways in platelet
      activation processes.

PMID- 9020891
TI  - Epitope mapping of a monoclonal antibody to human glutathione transferase P1-1
      the binding of which is inhibited by glutathione.
AB  - Although the three-dimensional structure of human glutathione transferase (GST)
      P1-1 crystallized with a GSH analogue has been reported, its structure in the non
      complexed form has not been determined. Four monoclonal antibodies to GST P1-1
      were produced to facilitate structural analysis. Of these, one, clone d-1 of
      IgG2a isotype, dose-dependently inhibited the activity of GST P1-1 but did not
      affect the activities of either GST A1-1 or M1-1. On immunoblotting, the antibody
      reacted strongly with GST P1-1 and weakly with rat GST-P and mouse GST-II,
      indicating cross-reactivity with Pi-class forms but preferential reactivity with
      GST P1-1. When GST P1-1 and the antibody were incubated in the presence of 60
      microM GSH, no inhibition of activity was found, whereas 1-chloro-2,4
      dinitrobenzene had no effect at concentrations up to 10 microM. The binding of
      GST P1-1 to antibody adsorbed to Protein A-Sepharose was also prevented by both
      0.1 mM GSH and N-ethylmaleimide treatment. Trypsin digests of GST P1-1 were
      resolved by HPLC and a peptide that reacted with the antibody was detected by
      absorption experiments. N-Terminal amino acid sequencing revealed the peptide to
      be in the C-terminal portion of the enzyme, stretching from amino acid residues
      198 to 208. A synthetic peptide of this sequence also absorbed the antibody.
      These results suggest that both GSH bound to the active site and N-ethylmaleimide
      bound to the cysteine residue repress antibody binding to the C-terminal region.
      Thus this antibody may be useful for examining the steric configuration of the C
      terminal and other regions of GST P1-1 in the absence of GSH.

PMID- 9020892
TI  - Inhibition of spermidine synthase gene expression by transforming growth factor
      beta 1 in hepatoma cells.
AB  - We screened genes responsive to transforming growth factor-beta (TGF-beta 1)
      protein in a human hepatoma cell line (Hep3B) using a PCR-mediated differential
      display technique, in order to investigate the mechanisms involved in TGF-beta
      induced growth suppression. We found a gene that was down-regulated by TGF-beta 1
      to be completely identical in an approx. 620 bp segment to the gene for the
      enzyme spermidine synthase, which mediates the conversion of putrescine into
      spermidine. Both spermidine synthase mRNA expression and its enzyme activity were
      decreased after TGF-beta 1 treatment of Hep3B cells. The inhibition of spermidine
      synthase gene expression by TGF-beta 1 protein was also observed in other
      hepatoma cell lines. The expression of genes for other biosynthetic enzymes in
      polyamine metabolism (ornithine decarboxylase and S-adenosylmethionine
      decarboxylase) was also inhibited to the same extent as for spermidine synthase,
      while the gene expression of spermidine/spermine N1-acetyltransferase, a
      catabolic enzyme, was relatively resistant to TGF-beta 1. Spermine levels in
      Hep3B cells were decreased by TGF-beta 1 treatment, although the levels of
      spermidine and putrescine were unchanged, probably due to compensation by
      remaining spermidine/spermine N1-acetyltransferase activity. Exogenously added
      spermidine or spermine, but not putrescine, partially antagonized the growth
      inhibitor effects of TGF-beta 1 on Hep3B cells. Our data suggest that down
      regulation of gene expression of the enzymes involved in polyamine metabolism,
      including spermidine synthase, may be associated with the mechanism of TGF-beta
      induced growth suppression.

PMID- 9020893
TI  - Sarco/endoplasmic reticulum Ca2+-ATPase isoforms: diverse responses to acidosis.
AB  - The effects of acidic pH on the kinetics of Ca2+-ATPase isoforms from
      intracellular membranes of skeletal muscle, cardiac muscle, cerebellum and blood
      platelets were studied. At neutral pH, all four Ca2+-ATPase isoforms exhibited
      similar Ca2+-concentration requirements for half-maximal rates of Ca2+ uptake and
      ATP hydrolysis. A decrease in the pH from 7.0 to 6.0 promoted a decrease in both
      the apparent affinity for Ca2+ [increasing half-maximal activation (K0.5)] and
      the maximal velocity (Vmax) of Ca2+ uptake. With skeletal muscle vesicles these
      effect were 5 to 10 times smaller than those observed with all the other
      isoforms. Acidification of the medium from pH 7.0 to 6.5 caused the release of
      Ca2+ from loaded vesicles and a decrease in the amount of Ca2+ retained by the
      vesicles at the steady state. With the vesicles derived from skeletal muscle
      these effects were smaller than for vesicles derived from other tissues. The rate
      of passive Ca2+ efflux from skeletal and cardiac muscle vesicles, loaded with
      Ca2+ and diluted in a medium containing none of the ligands of Ca2+-ATPase, was
      the same at pH 7.0 and 6.0. In contrast, the rate of Ca2+ efflux from cerebellar
      and platelet vesicles increased 2-fold after acidification of the medium. The
      effects of DMSO, Mg2+ with Pi and arsenate on the rate of Ca2+ efflux varied
      among the different preparations tested. The differences became more pronounced
      when the pH of the medium was decreased from 7.0 to 6.0. It is proposed that the
      kinetic differences among the Ca2+-ATPase isoforms may reflect different
      adaptations to cellular acidosis, such as that which occurs during ischaemia.

PMID- 9020894
TI  - Recoverin inhibits the phosphorylation of dark-adapted rhodopsin more than it
      does that of bleached rhodopsin: a possible mechanism through which rhodopsin
      kinase is prevented from participation in a side reaction.
AB  - In its resting state rhodopsin kinase is present in an inactive from and is
      activated after interaction with light-activated rhodopsin (Rho*). The activated
      rhodopsin kinase then phosphorylates Rho* but is also able to catalyse the
      phosphorylation of dark-adapted rhodopsin. A consequence of the latter behaviour
      of the activated kinase is that at low levels of bleach a large number of
      phosphoryl groups are incorporated per mol of Rho*. Recoverin- and Ca2+-dependent
      inhibition of rhodopsin kinase was found to be inversely related to the extent of
      bleaching; the lower the fraction of rhodopsin bleached, the greater the
      inhibition. The IC50 of recoverin is approx. 1 microM at a 0.2% level of bleach
      and about 5 microM in a fully bleached sample. The inhibitory effect of recoverin
      was studied separately on the phosphorylation of rhodopsin and Rho*. The
      formation of phosphorylated rhodopsin was inhibited 4.5-fold more strongly than
      that of phosphorylated Rho*. These results are interpreted to suggest that one of
      the roles of the recoverin-dependent regulation of the activity of rhodopsin
      kinase is to prevent the enzyme from participating in the unwanted
      phosphorylation of dark-adapted rhodopsin, directing it to fulfil its 'correct'
      function of quenching the transduction activity of Rho*.

PMID- 9020895
TI  - Nomenclature for sugar-binding subsites in glycosyl hydrolases.

PMID- 9020896
TI  - K-ras codon 12 and 61 point mutations in bromodeoxyuridine- and N
      nitrosomethylurea-induced rat renal mesenchymal tumors.
AB  - The mutagenic thymidine analog bromodeoxyuridine (BrdUrd) may incorrectly
      incorporate opposite deoxyguanine in DNA, then pair with deoxyadenosine during
      subsequent replication. It appears to preferentially target the 3'-G of 5'-NGGN
      3' sequences in mammalian cells in culture to induce G-->A transitions. Ras genes
      should therefore be vulnerable to activation by mutation at glycine codons 12
      (GGT) and/or 13 (GGC) by misincorporation of BrdUrd. There is limited evidence
      that BrdUrd may be carcinogenic or co-carcinogenic in rats: three renal
      mesenchymal tumors, a tumor known to be associated with activating mutations in
      the c-K-ras-2 oncogene, were reported in 87 rats treated with BrdUrd alone, while
      N-nitrosomethylurea (NMU) alone or NMU + BrdUrd resulted in incidences of 12/52
      and 26/76, respectively, against a zero incidence in untreated rats. We analyzed
      renal mesenchymal tumors from rats treated with BrdUrd for mutations in K-ras
      exons 1 and 2 and compared the prevalence and spectrum of mutations with those
      found in comparable tumors induced with NMU. DNAs from 22 paraffin-embedded renal
      mesenchymal tumors from rats treated 12-15 months earlier with BrdUrd (three
      specimens) or NMU (11 specimens) or both agents sequentially (eight specimens)
      were amplified by PCR. The base sequence of codons 12-13 and 59-63 of K-ras was
      determined by the dideoxynucleotide method. Sequencing results were confirmed by
      allele-specific oligonucleotide hybridization. Two of three tumors that appeared
      in rats given BrdUrd alone contained both a codon 12 GGT-->GAT transition and a
      codon 61 CAA-->CTA transversion. One tumor induced by NMU alone also showed a
      codon 12 GGT-->GAT mutation, while only wild type sequence could be demonstrated
      in the codon 12-13 region in the remaining ten such tumors. Three NMU-induced
      tumors also showed codon 61 CAA-->CTA mutations, while the remaining tumors had
      wild type sequence. While the GGT-->GAT transitions identified in tumors from
      BrdUrd-treated rats are consistent with BrdUrd mutagenesis by misincorporation,
      the co-occurrence of CAA-->CTA transversions, the overall low prevalence of
      mutations, and the lack of any difference in mutation spectrum between tumors
      induced by NMU and those that occurred in BrdUrd-treated rats suggests that in
      both groups the mutations that did occur did not result from a direct effect of
      either agent.

PMID- 9020897
TI  - Cytogenetic damage in exfoliated oral mucosal cells and circulating lymphocytes
      of patients suffering from precancerous oral lesions.
AB  - One hundred patients suffering from oral submucous fibrosis (OSF), oral
      leukoplakia (OL) and oral lichen planus (OLP) were studied for the cytogenetic
      damage in oral mucosal cells and in circulating lymphocytes along with their
      habit patterns. It was observed that OSF was largely associated with betel nut
      containing masticants while OL was associated with chewing or smoking habit. It
      was further observed that their exfoliated oral mucosal cells had significantly
      higher numbers of micronucleated (Mn) cells as compared to these of healthy
      normal subjects without any chewing or smoking habit. Similar cytogenetic damage
      in the form of increased sister chromatid exchanges (SCE) was observed in
      circulating lymphocytes indicating that the carcinogenic agents produce damage
      not only in target tissue but also in other host cells such as circulating
      lymphocytes.

PMID- 9020898
TI  - MHC class II antigen-associated invariant chain on renal cell cancer may
      contribute to the anti-tumor immune response of the host.
AB  - To investigate the association between renal cell cancer (RCC) and the host
      immune system, we examined the expression of invariant chain (Ii) and HLA-DR on
      renal cancer. Immunohistochemically, Ii was detected in 53 of the 60 cases of
      RCC. Significant correlation was found between the expression of Ii and the
      degree of lymphocyte infiltration. Flow cytometric analysis for HLA-DR and Ii on
      RCC cell line (ACHN) showed no positive cells, whereas interferon (IFN)-K
      treatment induced HLA-DR. Immunoprecipitation showed the presence of cytoplasmic
      Ii in ACHN cells. In addition, IFN-K-treated ACHN cells showed more intense
      signals than untreated cells. These results suggest that Ii associated with class
      II antigens on RCC may contribute to the anti-tumor immune response of the host
      and that IFN-K, which is administered for the treatment of cancer, may increase
      the immunogenicity of RCC.

PMID- 9020899
TI  - In vitro evaluation of Taxol combined with radiations in human squamous cell
      carcinoma spheroids.
AB  - The effect of Taxol on the radiation sensitivity of human squamous carcinoma of
      the head and neck region was determined in vitro, using clonogenic assays and
      multicellular tumor spheroids (MTS). Radiosensitivity parameters were determined
      by alpha and beta for clonogenic assays, and by the residual/control volume
      ratios at 2 Gy (RSV2) and the dose inducing 50% decrease in MTS number (SCD50)
      for spheroids. In HTB43 and CAL27 colonies, the combination was antagonist. In
      spheroids, Taxol induced a decrease of RSV2 and SCD50 in HTB43 and CAL27 MTS and
      their combinations with radiation were synergistic and additive, respectively.
      Therefore, the different results obtained by clonogenic assays and MTS may
      suggest higher drug incorporation through the multiple cell layers of the
      spheroids than in monolayers.

PMID- 9020900
TI  - Mistletoe lectins I, II and III induce the production of cytokines by cultured
      human monocytes.
AB  - The three mistletoe (Viscum album L.) lectins. ML I, ML II and ML III, were
      tested on their ability to enhance the secretion of the cytokines tumor necrosis
      factor (TNF)alpha, interleukin (IL)-1 alpha, IL-1 beta and IL-6 by human
      monocytes obtained from healthy donors. At lectin concentrations from 0.02 to
      20/pg ml (100-10,000-fold lower than those showing toxic effects), stimulations
      of cytokine production several-fold over control values were observed. The
      immunoactivating concentrations by the three lectins were found different for
      each donor. At toxic concentrations, the amounts of IL-1 alpha, IL-1 beta and to
      a less extent of TNF alpha in monocytes supernatants were particularly high. The
      data are discussed in relationship with the cytotoxic and immunoactivating
      effects of mistletoe lectins and their interest in cancer treatment.

PMID- 9020901
TI  - The effect of TGF-beta 1 on cell proliferation and proteoglycan production in
      human melanoma cells depends on the degree of cell differentiation.
AB  - The effect of transforming growth factor beta 1 (TGF-beta 1) on cell
      proliferation, colony formation in soft agar and synthesis and structure of
      proteoglycans was studied in three human melanoma cell lines at different stages
      of differentiation: SK-mel-1.36-1-5 (early), SK-mel-3.44 (intermediate) and SK
      mel-23 (late). TGF-beta 1 potently inhibited cell growth in monolayer as well as
      in soft agar. TGF-beta 1 increased the release of sulfated proteoglycans into the
      medium, including the cell-specific melanoma proteoglycan, mel-PG, and induced
      changes in disaccharide composition and sulfation of the glycosaminoglycan
      chains. In all the cases, the effect of TGF-beta 1 was more pronounced in the
      most undifferentiated cell line SK-mel-1.36-1-5 than in the SK-mel-3.44, whereas
      it had no effect on the most differentiated SK-mel-23 cells.

PMID- 9020902
TI  - Tiazofurin enhances the anabolism and toxicity of 5-fluorouracil.
AB  - Tiazofurin, a clinically active anticancer agent, is undergoing additional
      clinical testing in combination with other agents. We found that tiazofurin is an
      effective biochemical modulator of 5-fluorouracil anabolism. Pretreatment of
      cultured L1210 cells with tiazofurin at concentrations of 1-100 microM results in
      an increase in the rate of conversion of 5-fluorouracil to phosphorylated
      metabolites. Concentrations of tiazofurin effective in increasing 5-fluorouracil
      anabolism cause a corresponding increase in the 5-phosphoribosyl-1-pyrophosphate
      pool. Studies in mice show that tiazofurin increases the lethal toxicity of 5
      fluorouracil and increases the antitumor effectiveness of low doses of 5
      fluorouracil: however, the combination is not more effective than an optimal dose
      of 5-fluorouracil given alone. These results indicate that caution should be
      exercised in the concurrent use of tiazofurin with other drugs, particularly 5
      fluorouracil, that require 5-phosphoribosyl-1-pyrophosphate for activation or
      that are affected by a decrease in pyrimidine nucleotide synthesis.

PMID- 9020903
TI  - Liposome-delivered 131I-labelled Zn(II)-phthalocyanine as a radiodiagnostic agent
      for tumours.
AB  - 131I-Zn(II)-phthalocyanine (ZnPc) incorporated into unilamellar liposomes has
      been systemically injected to mice bearing a transplanted MS-2 fibrosarcoma.
      Biodistribution studies show that the pharmacokinetic behaviour of 131I-ZnPc is
      very similar to that defined for the parent molecule ZnPc including a serum half
      life of ca. 12 h, a high recovery from liver and spleen and minimal accumulation
      in kidney and brain. The most important pharmacokinetic parameter is represented
      by the high tumour/ muscle ratio of 131I-ZnPc concentration (ca. 9 at 24 h post
      injection). These results suggest the possible use of the radiolabelled
      derivative for a real-time non-invasive monitoring of the ZnPc concentration in
      the tumour and peritumoural tissue during photodynamic therapy.

PMID- 9020904
TI  - Effect of cis-unsaturated fatty acids on cellular oxidant stress in macrophage
      tumor (AK-5) cells in vitro.
AB  - Cis-unsaturated fatty acids (c-UFAs) induced decreased survival of macrophage
      tumor (AK-5) cells in vitro. The cytotoxic action of c-UfAs was associated with
      an increase in free radical generation and lipid peroxidation process. In
      addition, exposure of AK-5 cells to various c-UFAs for a short period (1 h)
      decreased the cellular concentrations of anti-oxidants: superoxide dismutase
      (SOD), catalase, glutathione peroxidase, glutathione reductase, glutathione and
      vitamin E. However, prolonged (24 h) exposure of AK-5 cells to c-UFAs enhanced
      the levels of SOD with little or no change in the concentrations of catalase,
      glutathione peroxidase and glutathione reductase. These results indicate that c
      UFAs can enhance free radical generation and lower the concentrations of various
      anti-oxidants in the tumor cells which may explain the cytotoxic action of c
      UFAs.

PMID- 9020905
TI  - Effect of aflatoxin B1-8,9-epoxide-DNA adducts on transcription of a supF gene
      fragment.
AB  - A linearized template, obtained from the vector pGEM-3Zf(+) containing a supF
      gene fragment, was treated with aflatoxin B1-8,9-epoxide (AFB1 epoxide) and
      transcription in vitro was then studied. The template functions of both strands
      of the supF gene were similarly inhibited as shown by transcription with both T7
      and SP6 RNA polymerases. This inhibition was dose-dependent and affected the
      elongation step more extensively than the initiation step. Gel electrophoretic
      analysis of RNA formed by T7 RNA polymerase indicated that template treated with
      different AFB1 epoxide doses yielded the same three major truncated RNA
      fragments. Sequence analysis showed that these major sites of RNA truncation
      occurred in the vicinity of adjacent guanine residues in the template.

PMID- 9020906
TI  - Nicotinamide-induced modification of hepatic MFO systems in tumour-bearing rats,
      treated with anti-cancer drugs.
AB  - Chemotherapeutic drugs like cyclophospamide (100 mg/kg b.wt.) and 5-fluorouracil
      (120 mg/kg b.wt.) caused significant inhibition in cytochrome P450 (cytP450)
      dependent hepatic microsomal drug metabolising enzymes in rats. A similar
      decrease in these enzyme activities was also seen in the host liver of tumour
      bearing animals. However, a non-toxic, endogenous (vitamin B3) metabolite,
      nicotinamide (100 mg/kg b.wt.) could effectively restore the hepatic drug
      metabolising enzyme levels back to control values in tumour-bearing animals
      treated with cyclophospamide and 5-fluorouracil.

PMID- 9020907
TI  - Expression of integrin subunits in normal and malignant human salivary gland cell
      clones and its regulation by transforming growth factor-beta 1.
AB  - In this study, we have examined the expression of integrin subunits in normal and
      malignant human salivary gland cell clones as well as its regulation by
      transforming growth factor-beta 1 (TGF-beta 1). By the analysis using
      immunofluorescence staining, an SV40 immortalized normal human salivary gland
      duct cell clone (NS-SVDC) with no tumorigenic ability by s.c. implantation into
      nude mice was identified to express the integrin beta 1, alpha 2, alpha 3 and
      alpha 6 subunits on the cell surface, while the expression of these subunits,
      except for beta 1 subunit, was reduced or completely diminished in a neoplastic
      human salivary gland duct cell clone (HSGc) with tumorigenic but not metastatic
      potential in nude mice and metastatic cell clones derived after in vitro exposure
      of HSGc to N-methyl-N-nitrosourea. In addition, immunoblot analysis also
      exhibited the same results as those obtained with immunofluorescence staining.
      The alpha 1 subunit was not demonstrable in any of the cell clones by both
      techniques. TGF-beta 1 augmented the expression of the beta 1 subunit in NS-SV
      DC, while HSGc and metastatic cell clones demonstrated no changes in the
      expression of the beta 1 subunit in response to TGF-beta 1. These findings,
      therefore, suggest that there is an inverse relationship between the malignancy
      and the expression mode of integrin subunits, especially alpha 2 subunit, in
      human salivary gland cell clones with varying degrees of malignant potential, and
      that TGF-beta 1 is a positive regulatory factor in the expression of the beta 1
      subunit in normal but not malignant cell clones.

PMID- 9020908
TI  - The cancer-promoting potential of fumonisin B1 in rat liver using
      diethylnitrosamine as a cancer initiator.
AB  - The cancer-promoting potential of fumonisin B1 (FB1) was investigated by feeding
      different dietary levels (10, 50, 100, 250, 500 mg FB1/kg) to diethynitrosamine
      (DEN)-initiated rats for 21 days. Dietary levels containing 50 mg FB1/kg and
      higher, markedly increased the number and size of the placental form of
      glutathione-S-transferase-positive (GSTP+) foci in the liver of the rats. The
      cancer-promoting activity of FB1 was associated with an inhibitory effect on
      partial hepatectomy (PH)-induced regenerative hepatocyte proliferation, as the
      incorporation of 3H-labelled thymidine was significantly (P < 0.05) reduced by
      those FB1-containing diets that exhibited cancer promotion. In vitro studies on
      the mitogenic activity of epidermal growth factor (EGF) in primary rat
      hepatocytes further supported the in vivo data in that FB1, similar to other
      cancer promoters such as phenobarbital and 2-acetylaminofluorene (2-AAF), alters
      growth stimulatory responses in primary hepatocytes. No significant (P > 0.05)
      changes in the sphinganine/sphingosine (Sa/So) ratio were observed in the liver
      of the rats fed the lowest FB1-containing diet (50 mg FB1/kg diet) that effected
      cancer promotion. The present study indicated that FB1 exhibited cancer-promoting
      activity in the absence of adverse hepatotoxic effects and at dietary levels that
      failed to effect cancer initiation.

PMID- 9020909
TI  - A comparative study on the effect of MNU on human lymphocyte cultures in vitro
      evaluated by O6-mdG formation, micronuclei and sister chromatid exchanges
      induction.
AB  - N-Nitroso-compounds are a large group of chemicals present in a number of
      environmental sources and many of them are mutagens as well as carcinogens in
      experimental animals. Among the known N-nitroso-compounds, N-nitroso-N-methylurea
      (MNU) is a strong mutagen. In this study an effort has been made to compare the
      ability of MNU to methylate the O6-guanosine site in DNA and to induce
      micronuclei and sister chromatid exchanges in human lymphocyte cultures in vitro.
      To quantitate O6-methyldeoxyguanosine (O6-mdG) a highly sensitive immunoassay,
      immuno-slot-blot (ISB), has been used. For the evaluation of micro nuclei (MN)
      the cytokinesis block micronucleus method has been used. Different concentrations
      (75, 100, 125 micrograms/ml) were tested. At the highest concentration tested for
      the MN induction, 125 micrograms/ml, the occurrence of binucleates and micro
      nuclei is higher than twice in relation to control and a reduction in NDI is also
      observed. The same concentrations were used for the estimation of sister
      chromatid exchanges (SCEs) induction. The mean number of SCEs at 125
      micrograms/ml is almost three times that of the control level. The concentrations
      tested for the quantitation of O6-mdG were 200, 300 and 400 micrograms/ml and
      this was done because for the test system we used and for the given experimental
      conditions the first indication of O6-mdG formation was at 200 micrograms/ml. Our
      results show that methylation of O6-guanosine increases with concentration and at
      400 micrograms/ml the concentration of O6-mdG is 5.83 fmol/microgram DNA, while
      at the control level it is 2.40 fmol/microgram DNA. Since O6-mdG formation is
      observed in higher concentrations than those of MN and SCE induction it would be
      interpreted that O6-mdG levels are not correlated with the studied cytogenetic
      effects although one has to take into consideration the total promutagenic
      lesions in DNA, induced by MNU, as well as AGT repair activity.

PMID- 9020910
TI  - Induction of rat hepatic cytochrome P4501A and P4502B by the methoxsalen.
AB  - The effect of methoxsalen, the inhibitor of the hepatic mixed function oxidase,
      on the expression of liver cytochrome P450s was examined in rats. Administration
      of methoxsalen to rats significantly increased the hepatic content of P450 and
      activities of microsomal ethoxyresorufin O-deethylase (EROD), methoxyresorufin O
      demethylase (MROD), pentoxyresorufin O-dealkylase (PROD), a representative
      activity of P4501A1, P4501A2 and P4502B1/2, respectively, in a dose-dependent
      manner. In contrast, there was no effect on the P4502E1 catalyzed aniline
      hydroxylase. In the time-course experiment, methoxsalen exhibited a biphasic
      effect on EROD, MROD, and PROD activities, an initial inhibitory phase was
      followed by a phase of induction following a single treatment. Immunoblot
      analysis using anti-rat liver P4501A and P4502B revealed that increase in the
      apoprotein levels of P4501A1/2 and P4502B1/2 by methoxsalen was consistent with
      those in enzyme activity levels. Levels of mRNA of P4501A1/2 and P4502B1/2 were
      also increased by methoxsalen in Northern blot analysis. These results
      demonstrated that methoxsalen acts as an inducer of the hepatic microsomal mixed
      function oxidase; selective induction of P4501A and P4502B families involved
      increases in mRNA levels.

PMID- 9020911
TI  - Differential expression of c-jun and c-myc in N-nitroso diethylamine-induced
      hepatic oncogenesis in AKR mice.
AB  - Expression of c-jun, c-myc, c-fos and c-Ha-ras was examined and correlated with
      the various stages of N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis
      in male AKR mice. The treated groups were given NDEA 100 ppm, in drinking water
      for 120 days. The histopathology along with the expression of oncogenes were
      studied at different durations of treatment such as after 1 day, 3 days, 6 days,
      9 days, 15 days, 20 days 30 days, 60 days, 90 days and 120 days of treatment. The
      results of histological investigation indicate mild hyperplasia and
      anisonucleosis at 30 days of treatment and prominent pathological features from
      60 days onwards until the appearance of hepatocarcinoma at 120 days even without
      the development of any preneoplastic or neoplastic nodule. The results of the
      Northern blot hybridization clearly indicate an increased expression of c-jun
      from 15 days onwards. This overexpression of c-jun at such an early stage
      indicates its association with the events earlier than the neoplastic changes.
      However, the persistent overexpression of c-jun at all durations of treatment
      indicates its association with the events during the later stage of
      hepatocarcinogenesis, whereas c-myc overexpression starts from 30 days of
      treatment and persists until the end of the experiment, i.e. 120 days of
      treatment. However, the results of densitometric quantification indicate that the
      extent of increase expression of c-myc is less than that of c-jun expression
      until 1 month of treatment, after which the induction of c-myc exceeds the
      expression of c-jun. Thus, the overexpression of c-myc from 2 months onwards
      might be playing a critical role in maintenance of the malignant phenotype. On
      the other hand, the expressions of c-fos and c-Ha-ras do not have any alteration
      during NDEA treatment. Thus, our data demonstrate the involvement of c-jun and c
      myc in NDEA-induced hepatocarcinogenesis in AKR mice.

PMID- 9020912
TI  - Enhanced antitumour effect of photodynamic therapy by microtubule inhibitors.
AB  - The combination of photodynamic therapy (PDT) and the microtubule (MT) inhibitor,
      vincristine (VCR) or taxol, was studied in the CaD2 mammary tumour model in mice.
      Meso-tetra(di-adjacent-sulphonatophenyl) porphine (TPPS2a) was used as a
      photosensitizer. An enhanced antitumour effect was found when VCR, at an almost
      non-toxic dose (1 mg/kg1, was injected i.p. into the mice 6 h before PDT, while
      no such enhanced effect was observed when the same dose of VCR was given either
      12 or 24 h before PDT or immediately before PDT. Furthermore, it was found that
      the number of mitotic cells increased 4-5-fold 6 h after the injection of VCR
      into the mice. VCR did not enhance the sensitivity of normal skin to PDT.
      Combination of PDT and taxol was also studied. The antitumour activity of PDT
      could be increased by taxol when the drug (35 mg/kg) was administered i.p. either
      6 h prior to PDT or immediately after or before PDT. No significant enhancement
      in PDT efficiency was found when PDT with photofrin was combined with VCR.

PMID- 9020913
TI  - Prediction of lymph node metastasis in gastric cancer patients with neural
      networks.
AB  - Artificial neural networks are a kind of pattern classifiers, with growing
      acceptance in medical and biological research. We applied a single layer
      perceptron to data of 4302 patients from National Cancer Centre in Tokyo and
      compared the results to the Maruyama diagnostic system (MDS) and classic
      statistical analysis with logistic regression. While logistic regression reached
      no sensitivity and a specificity of 1.00 in median, MDS had a sensitivity of 0.74
      and a specificity of 0.75 an median. The perceptron reached a median sensitivity
      of 0.81 and a median specificity of 0.71.

PMID- 9020914
TI  - Activation of ras oncogenes during hepatocarcinogenesis induced by N
      nitrosodiethylamine: possible involvement of PKC and GAP.
AB  - The expression of H-ras and N-ras was found to be increased in liver of rats fed
      with the carcinogen N-nitrosodiethylamine (NDEA). There were, however, variations
      in time at which these were expressed and in the extent of expression of the two
      genes. N-ras appeared to be more aggressive than H ras. This overexpression could
      be correlated with an inhibition in the functioning of GTPase activating protein
      (GAP). The activity of GAP in increasing the intrinsic GTPase activity of p21RAS
      was found to be much less in NDEA-treated rats as compared to that in control
      rats. It was observed that GAP isolated from NDEA-treated rats was extensively
      phosphorylated by protein kinase C, and this might be the reason for its
      decreased activity. It is speculated that phosphorylated GAP helps keep the
      p21RAS in the more active GTP-bound state.

PMID- 9020915
TI  - A urochordate putative homolog of human EB1, the protein which binds APC1.
AB  - The human EBI protein has been cloned by virtue of its interaction with the C
      terminus of the APC (adenomatous polyposis coli) protein, whose C-terminal
      truncated forms have been shown to accompany sporadic and familial forms of
      colorectal cancer. We have cloned a putative EBI homolog from Botryllus
      schlosseri (Urochordata. Ascidiacea). The deduced protein is 287 amino acids
      long, and is identical with 48% of the residues in human EBI and 24-25% in two
      yeast hypothetical proteins. We propose that such a high degree of conservation
      among EBI homologs is indicative of an essential regulatory mechanism in
      eukaryotic cells.

PMID- 9020916
TI  - DNA alterations in sporadic colorectal tumors do not correlate with tumor staging
      diagnosed by the TNM system.
AB  - Blood normal and tumor tissue samples of 23 patients with sporadic colorectal
      tumors were screened for DNA alterations in the tumor relevant genes APC, K-ras,
      DCC and p53. Six different microsatellite regions were analyzed for instability
      by a new developed non-radioactive method. Somatic DNA alterations were found in
      17 tumor samples: 13 carried single or multiple changes in single genes; six
      carried alterations in microsatellites; two tumors showed tumor suppressor gene
      mutations in addition to microsatellite changes. We found no indications of
      correlations between current genetic models of colorectal tumor progression and
      the established TNM system for histopathological tumor classification.

PMID- 9020917
TI  - Inhibition of peritoneal dissemination of colon carcinoma in syngeneic mice
      immunized with interleukin-2-producing cells.
AB  - We have examined the antitumor effect of murine colon carcinoma cells engineered
      to produce human interleukin-2 (IL-2) in syngeneic mice. Subcutaneous inoculation
      of retrovirally-transduced cells with IL-2 gene formed small tumors, but they
      became regressed spontaneously. Consequently, the inoculated mice showed
      prolonged survival. Histological examination of the tumors derived from IL-2
      producers revealed predominant infiltration of macrophages around tumor necrotic
      masses. Thus, inoculation of IL-2-producing cells could protect the mice from
      subsequent subcutaneous or intraperitoneal challenges with wild-type cells,
      suggesting the induction of acquired immunity due to the effect of tumor
      vaccination.

PMID- 9020918
TI  - High titers of antibodies to two human polyomaviruses, JCV and BKV, correlate
      with increased frequency of chromosomal damage in human lymphocytes.
AB  - Associations of antibody titers to the JC and BK human polyoma viruses and the
      frequency of chromosome aberrations (CA) in human peripheral blood lymphocytes
      were studied. Study group consisted of 33 workers occupationally exposed to low
      doses of ionizing radiation and 11 control persons. There were no statistically
      significant differences in the JC and BK virus titer values between two groups of
      donors. It was found that JC and BK virus titers explained approximately 6% of
      total inter-individual variation in CA frequency. Such factors as alcohol abuse,
      age and, in this special group, exposure to ionizing radiation explained an
      additional 53% of the total variation in CA frequency. In six clean-up workers
      and one control, rogue cell (cells with multiple chromosome-type aberrations)
      were found. The incidence of rogue cells correlated significantly with JC and BK
      virus titers as well as a history of recent acute respiratory disease.

PMID- 9020919
TI  - Protective effect of rutin, a flavonol glycoside, on the carcinogen-induced DNA
      damage and repair enzymes in rats.
AB  - Administration of hepatocarcinogens aflatoxin B1 and N-nitrosodimethylamine to
      rats caused single-strand breaks in nuclear DNA. Inclusion in the diet of rutin,
      a naturally occurring phenolic flavonoid glycoside, significantly reduced the
      appearance of such breaks. The protection against DNA damage was found to be
      reduction in the induction of repair enzymes polymerase, DNA polymerase beta and
      DNA ligase. Even associated with poly(ADP-ribose) a marginal dose of rutin was
      effective in this regard. Since DNA damage and inefficient repair are expected to
      initiate the process of carcinogenesis, modulation by rutin of these parameters
      emphasizes the protective role of this flavonoid against carcinogenesis induced
      by chemical carcinogens.

PMID- 9020920
TI  - Differential nuclear matrix-intermediate filament expression in human prostate
      cancer in respect to benign prostatic hyperplasia.
AB  - We have characterized the changes in composition of the nuclear matrix
      intermediate filament complex (NM-IF) isolated from prostate cancer (PCa),
      compared with benign prostatic hyperplasia (BPH). We prepared the NM-IF from ten
      patients undergoing radical retropubic prostectomy; the benign hyperplastic
      tissue was obtained from the prostate lobe contralateral to the cancer zone.
      Several quantitative and qualitative changes have been identified. Three new
      proteins of molecular weight 48, 47 and 29 kDa and isoelectric point 6.0, 4.9 and
      6.4, respectively, were detected in PCa, referred to here as P8, P5 and NM-1, P8
      was present in all ten of the tumors examined, P5 was expressed in 9/10 PCa;
      conversely, they were present in only one and two BPH, respectively; NM-1 was
      found in eight tumors out of nine and never in BPH. These proteins are expressed
      in moderately differentiated malignant cells, suggesting that the proteins of the
      NM-IF complex can be interesting biomarkers for prostate cancer. Immunoblot
      analysis shows that P8 and P5 proteins belong to the IF superfamily. This
      observation, taken together with previous data obtained by our and other groups,
      suggests that the characterization of NM-IF protein changes could also shed light
      on mechanistic aspects of cancer progression.

PMID- 9020921
TI  - Adenosine deaminase activity in patients with the intestinal type of gastric
      carcinoma.
AB  - Adenosine deaminase activity was studied in tissue slices taken endoscopically
      from gastric mucosa of patients with the intestinal type of gastric carcinoma.
      The enzyme activity was measured in mucosal homogenates by determination of
      ammonia liberated from substrate during 10-min incubation. It was found that: (1)
      the enzyme activity of de novo gastric cancer was significantly lower than that
      of recurrent cancer of the gastric remnant; and (2) the enzyme activity of
      uninvaded gastric mucosa surrounding the neoplastic lesion of non-operated
      stomach was significantly lower than of the gastric mucosa of partially resected
      stomach due to malignancy. Since the enzyme activity in gastric cancer and
      surrounding uninvaded gastric mucosa correlated well with the advance of
      neoplastic disease estimated by ultrasonography examination, we speculate that
      some systemic factors associated with tumor progression might be implicated in
      the regulation of adenosine deaminase activity.

PMID- 9020922
TI  - Relationship between the inhibition of azidopine binding to P-glycoprotein by MDR
      modulators and their efficiency in restoring doxorubicin intracellular
      accumulation.
AB  - Using three different cell lines exhibiting the MDR phenotype, we have studied
      the ability of eight different modulators to restore doxorubicin intracellular
      accumulation and to inhibit azidopine binding to membrane extracts. One cell line
      was of human origin (KB VI) and two of murine origin, overexpressing two
      different isoforms of the mdrl gene (C6 IV and C6 0.5). The modulators were
      distributed in different drug classes: cyclosporine A and PSC-833, quinine and
      quinidine, nifedipine and nicardipine, and verapamil and S-9788. We observed that
      there was no strict parallelism between restoration of doxorubicin intracellular
      accumulation and inhibition of azidopine binding. However, when considering
      separately each group of drugs, it appeared that the most potent drug in
      inhibiting azidopine labelling of P-glycoprotein (P-gp) was also the most potent
      in restoring doxorubicin accumulation. This indicates that azidopine binding
      cannot be used as a general screening test for the identification of new
      modulators, but rather at the level of the selection of potent analogues within a
      chemical family. The three cell lines behaved similarly, indicating that the
      structural diversity of P-pgs did not influence the efficiency and binding of
      modulators.

PMID- 9020923
TI  - Compensatory modulation of GAP activity in response to oncogenic stimulation.
AB  - GAP is a key negative regulator of the receptor tyrosine kinase (RTK) signal
      transduction pathway. The purpose of this study was to determine if expression or
      activity of GAP is modulated by hyperstimulation of the RTK pathway. It was found
      that cells forced to express wild-type Ha-ras, viral Ha-ras, or v-src exhibit
      increased GAP activity as compared to control cells. In addition, a novel GAP
      isoform appears in all ras-expressing NIH3T3 cell clones. These data indicate
      that there is compensatory regulation of GAP in response to an increase in RTK
      pathway activity.

PMID- 9020924
TI  - Inhibition of lung tumor cell growth in vitro and mouse lung tumor formation by
      lovastatin.
AB  - The HMG-CoA reductase inhibitor, lovastatin (LOV), has been reported to inhibit
      Ras farnesylation and the growth of Ras-transformed cells. Mouse lung tumors and
      human lung adenocarcinomas often have activating mutations in K-ras alleles. In
      the present study, we determined whether LOV inhibited the growth in vitro of
      mouse (C10, E9, LM1, LM2, and 82-132) and human (NCl-H125, H292, H441, H460, and
      H661) nor-transformed and neoplastically transformed lung epithelial cells and
      whether growth inhibition was related to cell transformation or K-ras activation.
      LOV inhibited the growth of mouse and human lung cells, but cell sensitivities
      were unrelated to neoplastic transformation or K-ras mutation. In addition, we
      evaluated whether LOV could inhibit the formation of lung adenomas induced by the
      tobacco-specific nitrosamine, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) in mice. LOV was administered in the diet at 0, 40, 160, or 400 ppm ad
      libitum to male strain A/J mice beginning 1 week after lung tumor induction with
      NNK (10 mumol/mouse). Mice were euthanized 6 months later. Enumeration of lung
      tumors revealed that LOV did not affect tumor incidence or size, but
      significantly reduced tumor multiplicity in a dose-related manner. These data
      suggest that LOV can suppress the formation of NNK-induced lung tumors, possibly
      at an early promotional stage. This suppression does not appear to be related to
      either the presence of mutated K-ras or to changes in K-ras expression.

PMID- 9020925
TI  - The 12-lipoxygenase gene-transfected MCF-7 human breast cancer cell line exhibits
      estrogen-independent, but estrogen and omega-6 fatty acid-stimulated
      proliferation in vitro, and enhanced growth in athymic nude mice.
AB  - The estrogen-dependent, linoleic acid (LA)-unresponsive, MCF-7 breast cancer cell
      line was transfected with 12-lipoxygenase (12-LOX) cDNA (MCF-7/12-LOX cells). The
      transfectant stably expressed high levels of 12-LOX mRNA and protein, and
      secreted large quantities of 12-hydroxyeicosatetraenoic acid when cultured with
      arachidonate. The transfectant grew in vitro in the absence of estrogen, and its
      growth was stimulated by LA. The MCF-7/12-LOX cells formed small solid tumors
      when injected into the mammary fat pads of ovariectomized nude mice. Despite this
      estrogen independence, MCF-7/12-LOX cell growth was stimulated further by
      estradiol both in vitro and in vivo, and to a greater extent than parental MCF-7
      cells.

PMID- 9020926
TI  - Role of tissue antioxidant defence in thyroid cancers.
AB  - Reactive oxygen species (ROS), consisting mainly of superoxide, hydrogen peroxide
      and hydroxyl radical, have been implicated in many diseases including cancer. ROS
      have been known to play an important role in the initiation and promotion of
      multistage carcinogenesis. The cellular antioxidant defence plays a crucial role
      in neoplastic disease. However, very little is known about the tissue antioxidant
      defence in thyroid cancers. We therefore undertook a study to assess the role of
      ROS in the pathogenesis of thyroid cancers. Our samples consisted of post
      operated thyroid tissues (normal, goiters, follicular adenomas, follicular
      carcinomas and papillary carcinomas). The parameters studied were lipid
      peroxidation (LP), antioxidant enzymes--superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPx)--and non-protein thiols (GSH). Compared to
      normal thyroid no changes were seen in goiters. LP was significantly higher in
      adenomas (16%) and carcinomas (60-69%). SOD was decreased by 15% in adenomas
      while in carcinomas it increased by 9-12%. GPx was raised in carcinomas by 10
      21%. Follicular carcinomas showed a 4% increase in CAT activity while GSH was
      raised in adenomas and papillary carcinomas by 17%. Thus, in adenomas (initial
      stage) involvement of superoxide radicals and in carcinomas (later stage)
      hydrogen peroxide and, possibly, hydroxyl radical involvement cannot be ruled
      out. These ROS may be responsible for elevated LP observed in adenomas and
      carcinomas.

PMID- 9020927
TI  - The skin as an organ of immunity.
AB  - During evolution, the skin has developed a specific immunological environment
      that is known as the skin immune system (SIS). A substantial number of
      immunological phenomena exemplify the special place the skin occupies as a
      peripheral immune organ. These include the continuous exposure to sun rays, with
      subsequent immunological consequences, an area of investigation known as
      photoimmunology. Also special is the presence of a dense network of dendritic
      antigen-presenting cells (Langerhans cells) in the epidermis, which are
      functionally related to the skin-specific phenomenon of the contact allergy type
      of delayed hypersensitivity. The acronym SIS is designed to give a complete
      picture of the skin's functions as an immunological organ, and includes the
      humoral systems in addition to the cellular subsets taking part in it. In this
      article, the history of the development of immunological concepts of skin is
      exemplified with some recently explored areas of immunodermatological research.

PMID- 9020928
TI  - Cadherins and Langerhans cell immunobiology.
AB  - Langerhans cells represent the epidermal contingent of a family of potent
      accessory cells termed 'dendritic cells'. Langerhans cells (and perhaps related
      cells in the dermis) are thought to be required for immune responses directed
      against foreign antigens and neoantigens that are encountered in skin. The 'life
      cycle' of the Langerhans cell is characterized by at least two distinct stages.
      Langerhans cells in epidermis (the 'sentinels') can ingest particulates and
      process antigens efficiently, but are weak stimulators of unprimed T cells. In
      contrast, Langerhans cells that have been induced to migrate to lymph nodes after
      contact with antigen in epidermis (the 'messengers') are not phagocytic and have
      limited antigen-processing capabilities, but are potent stimulators of naive T
      cells. If Langerhans cells are to fulfil both their 'sentinel' and 'messenger'
      roles, they must be able to persist in epidermis for considerable periods, and
      also be able to exit epidermis in a controlled fashion after exposure to antigen.
      Thus, regulation of Langerhans cell-keratinocyte adhesion represents a key
      control point in Langerhans cell trafficking and function. Langerhans cells
      express E-cadherin, a homophilic adhesion molecule that is prominently
      represented in epithelia. Keratinocytes also express this adhesion molecule, and
      E-cadherin clearly mediates adhesion of murine Langerhans cells to keratinocytes
      in vitro. We presume that E-cadherin is involved in the localization of
      Langerhans cells in epidermis. Murine thymocytes also express E-cadherin early in
      the course of their development, and it is likely that E-cadherin plays an as yet
      uncharacterized role in thymocyte-thymic epithelial cell adhesion and in T-cell
      development. Recently, it has also been demonstrated that some cutaneous T-cell
      lymphoma cell lines are E-cadherin+, so E-cadherin may also mediate clinically
      important leucocyte-epithelial interactions in disease states.

PMID- 9020929
TI  - The desmosome and hemidesmosome in cutaneous autoimmunity.
AB  - Epidermal blister formation is the hallmark of three cutaneous autoimmune
      diseases: pemphigus foliaceous (PF), pemphigus vulgaris (PV) and bullous
      pemphigoid (BP). In PF and PV, blistering is due to acantholysis (cell-cell
      detachment) in the subcorneal and suprabasal epidermal layers, respectively,
      while BP is characterized by detachment of the basal epidermal cells from the
      underlying dermis. For several years, we have focused our research efforts on
      elucidating the pathogenic mechanisms operating in these bullous diseases. Early
      studies performed by our research group and others revealed that in all three
      diseases, the patients produce autoantibodies that bind to target antigens
      located on the surface of cells that are undergoing detachment. Thus it was
      hypothesized that these anti-epidermal autoantibodies played a role in initiating
      blister formation. We recognized that elucidating the normal mechanisms of
      epidermal cell-cell and cell-dermis adhesion would help us understand the
      abnormal epidermal cell detachment seen in these patients. We hypothesized that
      under normal conditions these adhesive mechanisms in the epidermis are complex
      and dynamic and mediated by the interaction of cell surface molecules unique to
      each layer of the epidermis. Also, we postulated that PV, PF and BP
      autoantibodies may cause cell detachment by impairing the function of their
      respective epidermal cell surfaces. Support for this hypothesis has come from
      recent studies which showed that PV and PF autoantibodies recognize distinct, yet
      related, desmosomal glycoproteins in the cadherin family of calcium-dependent
      adhesion molecules. The epidermal antigen in PV is desmoglein-3 (dsg3), while in
      PF it is desmoglein-1 (dsg1). These anti-epidermal autoantibodies have been shown
      to be pathogenic in passive transfer experiments. Neonatal mice injected with
      these antibodies develop intraepidermal blisters characteristic of the
      corresponding human disease. Autoantibodies in BP react with BP180 and BP230, two
      major components of the hemidesmosome, a cell structure involved in dermal
      epidermal adhesion. Recent passive transfer mouse model studies performed in our
      laboratory have shown that anti-BP180 antibodies can induce subepidermal
      blistering in the experimental animals. Moreover, the pathogenic mechanism was
      shown to be dependent on complement activation and recruitment of neutrophils to
      the dermal-epidermal junction. In conclusion, desmosomal glycoproteins are the
      targets of autoimmune injury in PV and PF. The anti-epidermal autoantibodies may
      cause intraepidermal blisters by impairing the function of dsg1 and dsg3. In BP
      the hemidesmosome is the target. It appears that antiBP180 antibodies cause
      subepidermal blister formation by triggering a complement- and neutrophil
      mediated inflammatory process.

PMID- 9020930
TI  - Pathogenesis of cutaneous T-cell lymphoma: implications for the use of
      recombinant cytokines and photopheresis.
AB  - Cutaneous T-cell lymphoma (CTCL) is a clonally derived, skin invasive malignancy
      of CD4+ cells with the phenotype of mature helper T cells. We previously
      demonstrated that the leukaemic form of CTCL (Sezary), is characterized by
      prominent immunological defects including depressed cell-mediated immunity. We
      also demonstrated increased production of T-helper type 2 (Th2) cytokines (IL-4,
      IL-5) and deficient Th1 cytokines (IL-2 and IFN-gamma) by their peripheral blood
      mononuclear cells (PBMC) and detected IL-4 and IL-5 mRNA within lesional skin of
      patients with all stages of CTCL. A marked defect in IL-12 production has also
      been noted, which may also play a role in depressed cell-mediated immunity. These
      results suggested that the malignant CD4+ cells were Th2 cells. Thus, the immune
      aberrations have been attributed to the cytokine abnormalities triggered by the
      malignant T-cell population. Because CTCL responds to biological response
      modification, we focused on strategies for reversing the cytokine and immune
      defects by in vitro testing of novel biological response modifiers. Our results
      indicate that IFN-alpha potently suppresses the abnormal IL-4 and IL-5
      production, that IL-12 can correct the deficient IFN-gamma production and cell
      mediated cytotoxicity, and that retinoids can enhance IFN-gamma and IL-12
      production. We also studied the in vitro growth characteristics of the malignant
      CD4+ cells and determined that IL-12 and IFN-alpha significantly suppress growth
      of these cells. These studies led to a phase I trial of IL-12 to treat CTCL.
      Also, we have determined that photopheresis produces a high clinical response
      rate among Sezary syndrome patients. This therapy not only augments functions of
      monocytes but also induces the malignant T cells to undergo a high rate of
      apoptosis. We discuss how these therapies might be employed in concert to produce
      the optimum desired anti-tumour effect.

PMID- 9020931
TI  - Is psoriasis induced by streptococcal superantigens and maintained by M-protein
      specific T cells that cross-react with keratin?
AB  - The evidence that T lymphocytes play a key role in the pathogenesis of psoriasis
      is now compelling. Eruption of psoriatic skin lesions coincides with epidermal
      infiltration and activation of T cells, and spontaneous or treatment-induced
      resolution of the lesions is preceded by the reduction or disappearance of
      epidermal T cells. An upregulation has also been demonstrated for various
      molecules associated with T-cell mediated inflammation, and treatments
      selectively directed against T cells have proved very effective. Infections with
      group A beta-haemolytic streptococci have been associated with onset of acute
      psoriasis and exacerbation of chronic psoriasis. Such infections are also
      frequently accompanied by erythematous skin rashes. Also, recent reports indicate
      that streptococcal superantigens can induce expression of cutaneous lymphocyte
      antigens (CLA), believed to play a major role in enabling T cells to migrate to
      the skin. Furthermore, T-cell lines isolated from psoriatic lesions may show
      strong reactivity to streptococcal antigens. We have postulated that psoriasis is
      an autoimmune disease mediated by T cells reacting to epitopes that are common to
      streptococcal M-proteins and keratins. To investigate this possibility,
      circulating T cells from 12 patients with active psoriasis, paired controls, and
      six patients with atopic dermatitis were challenged in vitro with five synthetic
      20aa (amino acid) M-peptides: production of IFN-gamma and IL-4 was analysed by
      ELISPOT and RT-PCR techniques. Four of these peptides shared five to six aa
      sequences with several type I keratins and one did not. In 10 of the 12 psoriasis
      patients, measurable IFN-gamma production could be induced by one or more of the
      four peptides that share sequences with keratins. A borderline response was
      observed in only four of the 18 controls: the dermatitis patients were all
      negative. The only peptide that shared 6aa with keratins was the one that induced
      a response in the psoriatic patients most frequently, and four of them showed the
      strongest response to this peptide while none of the controls reacted to it. In
      all instances negligible responses were observed to the control peptide that did
      not share sequences with keratins. Except for PHA-stimulated controls, IL-4
      responses could not be detected by either ELISPOT or RT-PCR and there was
      generally good agreement between the two techniques. A marked reduction in the M
      peptide-induced IFN-gamma responses was observed in the psoriasis patients during
      remission induced by UVB treatment, while their responses to streptokinase
      streptodornase were not affected. Thus, active psoriasis is associated with a Th1
      type response to short peptides with epitopes shared by streptococcal M-protein
      and keratin. This is consistent with the hypothesis that psoriasis may be induced
      and exacerbated in susceptible individuals by M-protein-specific Th1-like cells
      that cross-react with human epidermal keratin.

PMID- 9020932
TI  - Atopic dermatitis: immunobiology and treatment with immune modulators.
AB  - Atopic dermatitis (AD), a chronic inflammatory skin disease, is frequently seen
      in patients with a personal or family history of asthma and allergic rhinitis.
      Population studies suggest an increasing prevalence of AD in children since World
      War II, with 10-15% of the population being affected by AD at some time during
      childhood. In patients with moderate to severe AD, involvement can be life-long,
      causing significant interference with school, work and social interactions. The
      term atopic dermatitis was introduced to reflect the close association between AD
      and respiratory allergy. During the past decade, extraordinary progress has been
      made in our understanding of the immunopathogenesis of allergic diseases. In
      particular, this constellation of inherited illnesses has now been demonstrated
      to be associated with activation of a specific group of cytokine genes
      encompassing IL-3, IL-4, IL-5, IL-13 and granulocyte-macrophage colony
      stimulating factor (GM-CSF). The molecular basis for selective activation of this
      cytokine gene cluster and the immunological consequences are now being pursued
      actively by many laboratories. However, it is clear that allergic diseases result
      from a polygenic inheritance pattern which involves not only cytokine gene
      activation but also activation of other less well defined gene products.
      Furthermore, the clinical expression of allergic diseases is highly dependent on
      a complex interaction between the host and its environment, e.g. allergen
      exposure. The genetic predisposition to develop allergic responses may be similar
      in patients with AD and other allergic diseases, such as asthma. However,
      targeting of the allergic immune response may relate to the organ in which
      allergen sensitization first occurs; the capacity of immune effector cells, e.g.
      T lymphocytes, to home preferentially to the skin versus the respiratory mucosa;
      and the programmed response of resident cells, e.g. epithelial cells, to injury
      and inflammation. This review examines the cellular and immunological mechanisms
      that are thought to play an important role in the pathogenesis of chronic AD. An
      understanding of the immunological basis of AD is likely to have important
      clinical implications in our approach to the management of this common illness,
      and the development of immunomodulators for its treatment.

PMID- 9020933
TI  - Vectors--shuttle vehicles for gene therapy.
AB  - Gene therapy is being considered for the treatment of various inherited and
      acquired disorders. The basic premise of this new therapeutic modality is
      manipulation of gene expression towards a therapeutic end. The early development
      of the field focused on a technique called ex vivo gene therapy in which
      autologous cells are genetically manipulated in culture prior to transplantation.
      Recent advances have stimulated the development of in vivo gene therapy
      approaches based on direct delivery of the therapeutic gene to cells in vivo. The
      rate-limiting technologies of gene therapy are the gene delivery vehicles, called
      vectors, used to accomplish gene transfer. The most efficient vectors are based
      on recombinant versions of viruses with retroviral vectors serving as prototypes.
      This viral vector system has been exploited in ex vivo approaches of gene therapy
      in which cultured, dividing cells are transduced with the recombinant virus
      resulting in integration of the proviral DNA into the chromosomal DNA of the
      recipient cell. The use of retroviral vectors in gene therapy has been restricted
      to ex vivo approaches because of difficulties in purifying the virion and the
      requirement that the target cell is dividing at the time of transduction. More
      recently, vectors based on adenoviruses have been developed for in vivo gene
      therapy. These viruses can be grown in large quantities and highly purified.
      Importantly, they efficiently transduce the recombinant genome into non-dividing
      cells. Applications include in vivo gene delivery to a variety of targets such as
      muscle, lung, liver and the central nervous system. Clinical trials of in vivo
      delivery with adenoviruses have been undertaken for the treatment of cystic
      fibrosis.

PMID- 9020934
TI  - Use of microgenomic technology for analysis of alterations in DNA copy number and
      gene expression in malignant melanoma.
AB  - Chromosome abnormalities in human malignancies have identified the genomic
      location of several important growth-regulatory genes, including cellular
      oncogenes and tumour suppressor genes. Melanomas are characterized by recurring
      chromosome alterations, and it is important to identify those genes whose altered
      expression may be causally related to melanocytic transformation. This short
      report presents an overview of strategies used which combine the materials and
      technologies of the Human Genome Project with clinically directed studies of
      melanoma biology. The Human Genome Project combines various technologies,
      including cytogenetic, physical mapping, genetic mapping and DNA sequencing, in
      order to identify all of the human genes, but especially the 4000 estimated to
      contribute to human disease. This report focuses first on advances in genome
      technology that provide information on chromosome rearrangements and DNA copy
      number changes. This includes a discussion of chromosome microdissection as well
      as the microexcision of tissue specimens to gain insights into chromosome regions
      altered in association with melanocyte transformation. Next, there is a brief
      discussion of the generation and characterization of subtracted cDNA sublibraries
      which allow the identification of genes uniquely expressed in association with
      the transformed phenotype of human melanoma cells. Finally, we briefly discuss
      the feasibility of using a recently developed system for parallel examination of
      multiple genes based upon robotic printing of cDNAs on glass slides, and
      simultaneous two-colour fluorescence hybridization to study the expression
      patterns of cDNAs for their association with melanoma tumour suppression. The
      combination of these varied molecular technologies may provide insights into
      previously unrecognized genes involved causally in the pathobiology of this
      important neoplasm, and may provide new targets for clinical intervention.

PMID- 9020935
TI  - Gene therapy for HIV infection.
AB  - HIV-1 is the causative agent of acquired immune deficiency syndrome (AIDS) and is
      a major international health concern. The limited effectiveness of current
      antiviral therapies has led to the search for alternative treatments. One
      emerging field of medical treatment is termed human gene therapy. In principle,
      human gene therapy calls for the engineering of the cells from a medical patient
      with an agent that can potentially result in a therapeutic benefit to the
      patient. It has been suggested that gene therapy technology may be applied as an
      anti-HIV-1 agent. The term 'intracellular immunization' was suggested for
      strategies that work within a potential HIV-1 target cell to inhibit the
      productive infection of that cell by HIV-1. Various strategies based on this
      intracellular approach have been proposed and include the use of antisense, and
      transdominant HIV proteins. Both of these approaches can inhibit HIV-1 in vitro
      and a clinical trial has been proposed to test their effectiveness in vivo.

PMID- 9020936
TI  - High-efficiency recovery of immature haematopoietic progenitor cells with
      extensive proliferative capacity from human cord blood cryopreserved for 10
      years.
AB  - Cord blood is enriched with haematopoietic stem and progenitor cells which have
      high levels of proliferative, replating and expansion capacity in vitro.
      Cryopreserved cord blood stored for up to a few years has been used as a source
      of transplantable cells for related and unrelated allogeneic stem cell
      transplantation. Information on retrieval of immature and mature subsets of
      viable haematopoietic progenitor cells from long-term cryopreserved cord blood is
      not yet available. We therefore assessed the recovery of cord blood cells stored
      frozen in liquid nitrogen for up to 10 years. Calculations of efficiency of
      recovery were possible because the exact same culture conditions were used for
      pre-freeze and post-thaw cells with the serum and growth factors presently used
      being of similar potency to those used for the studies 10 years ago. High
      efficiency recovery of immature and mature progenitors was found even though a
      relatively unsophisticated freezing procedure had been used. Recovery of
      nucleated cells averaged 88% and that of granulocyte-macrophage (CFU-GM),
      erythroid (BFU-E) and multipotential (CFU-GEMM) progenitors averaged from 74 to
      91% for different populations, with some samples in each category being recovered
      at 100%. Recovery of immature progenitors responsive to stimulation in vitro with
      a colony stimulating factor plus the potent co-stimulating cytokine, steel
      factor, was also demonstrated, although the per cent recovery of such cells could
      not be calculated directly as steel factor was not available 9-10 years ago when
      the cells were originally frozen. While the cell populations assayed are not
      considered to represent long-term narrow repopulating cells, the data presented
      demonstrate that cells with very high proliferative capacity can be stored long
      term in cryopreserved form.

PMID- 9020937
TI  - Gene therapy for haematopoietic and lymphoid disorders.
AB  - Gene transfer into haematopoietic stem cells (HSC) has been investigated for
      treatment of genetic disorders, conferral of chemotherapy resistance and
      insertion of genes to inhibit HIV-1 replication. Methods have been available for
      almost a decade to transduce murine HSC using high-titre retroviral vectors and
      stimulation of HSC proliferation with cytokines such as IL-3 and IL-6.
      Unfortunately, attempts to replicate the high efficiency of gene transfer using
      canine or simian gene transfer/bone marrow transplantation models have
      consistently shown that only a small fraction (0.1-1%) of reconstituting HSC are
      transduced using protocols similar to those which are successful in murine
      models. Initial clinical trials using retroviral-mediated gene transfer into
      human HSC also produced minimal transduction frequencies. The dicotomous results
      may reflect differences in the cell cycle kinetics of murine HSC versus those of
      larger mammals or the density of receptors for the retroviral vectors on the
      cells. Attempts to increase the fraction of HSC which are in active cell cycle, a
      prerequisite for retroviral-mediated transduction, have used either combinations
      of recombinant cytokines, culture on marrow stromal layers, or alternative
      sources for HSC, such as mobilized peripheral blood stem cells or umbilical cord
      blood. Other efforts have used retroviral vectors packaged with either the Gibbon
      Ape Leukemia virus envelope or the Vesicular Stomatitis Virus G protein. To date,
      none of these methods has produced a significantly increased frequency of long
      term reconstituting HSC. Results using adeno-associated virus (AAV)-based vectors
      for HSC transduction have been conflicting, with the stable persistence of non
      integrated virus particles making interpretation of results difficult using in
      vitro assays. Therefore, clinical trials may best be directed toward disorders
      that may benefit from a small fraction of genetically corrected HSC. These would
      include disorders where progeny of corrected HSC would be expected to have a
      selective survival advantage (e.g. SCID, WAS, HIV, chemoresistance) or where a
      small fraction of corrected cells can have a direct clinical benefit (e.g. CGD,
      MPS). Further basic research into HSC biology and gene delivery vectors must
      continue for wider application, such as haemoglobinopathies and some lysosomal
      storage diseases.

PMID- 9020938
TI  - [Esophageal cancer and multiple primary cancer].
AB  - Two hundred eleven cases, 27.1%, of multiple primary cancers of esophagus and
      other organs were found in 778 cases of esophageal cancers which were treated in
      our institution. Among them, double cancer accounted for 92.9%, triple cancer
      accounted for 6.6% and quadruple cancer for 0.5%. As for the other organ of
      esophageal double cancer. 59.9% of them were head and neck, 25.1% were stomach,
      4.9% were colon and rectum, and remaining included liver, breast, lymphoma lung
      kidney etc. Head and neck cancers consisted with hypopharynx, tongue, larynx,
      oral floor and gingiva regarding incidence in its order. For discovering of
      double cancer in esophagus and other organs, 1. head and neck, stomach, colon and
      rectum, lung, liver etc. should be investigated preoperatively in the patients of
      esophageal cancer, 2. Esophagus should be examined preoperatively in the patients
      of these cancers, 3. Screening of esophageal cancer should be performed in the
      patients of high risks of esophageal cancer. As for the multiple primary cancer
      of esophagus and other organs, the balance of treatment should be considered to
      take the priority of the cancer limiting the prognosis.

PMID- 9020939
TI  - [Treatment of malignant melanoma: recent advances and perspectives].
AB  - Because malignant melanoma is a highly malignant neoplasm, correct diagnosis and
      appropriate treatment are essential to improve the prognosis. In the present
      paper the author summarizes the advancements in the therapy of malignant
      melanoma, reviewing papers recently published in this field. It is noteworthy
      that a narrow excision margin has been recommended even for the surgery of this
      neoplasm. This narrow margin has been approved by the prospective randomized
      trial performed by the WHO melanoma study group. The study group also confirmed
      that elective lymph node dissection is not significant in the improvement of the
      prognosis, when compared to the delayed lymph node dissection. Considering these
      findings, the author proposes a revised guideline for the treatment of malignant
      melanoma according to UICC stages. A brief comment is made on a new drug,
      fotemustine, that has an effect on brain metastases. In addition, high response
      rates obtained by the Dartmouth regimen (BCDT regimen), including tamoxifen, an
      estrogen antagonist, are reported. "Sequential" biochemoimmunotherapy based on a
      new concept of rational combination of chemotherapeutic and biologic agents seems
      highly effective against metastatic melanoma, showing more than 50% response
      rates. In the regimens, chemotherapy including CDDP is followed by administration
      of the cytokines, IL-2 and IFN-alpha. These regimens possibly induce specific
      and/or non-specific immune reactions against melanoma cells, which may contribute
      to the high response rates.

PMID- 9020940
TI  - [Squamous cell carcinoma and basal cell carcinoma].
AB  - Both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are very common
      in skin malignancy. Operative therapy is the first choice at the treatment for
      SCC and BCC in early stage. After excision for large skin tumor, occasionally we
      use skin flap or musculocutaneous flap or free flap. At the old patient of Stage
      III and IV SCC and BCC, sometimes reduction surgery is useful at the combination
      therapy. Radiation as adjuvant therapy is sometimes useful for not only SCC but
      also BCC. The clinical efficacy of CA (C' A') chemotherapy (CDDP, ADM or CBDCA,
      EPI-ADM), was evaluated on Stage III, IV SCC and BCC. The response rate was 63%
      in SCC and 75% in BCC.

PMID- 9020941
TI  - [Primary cutaneous lymphoma--mycosis fungoides].
AB  - Malignant lymphoma of the skin is a type of extranodal lymphoma with a benign
      prognosis, in which the main organ involved is the skin. Some 80-90% of the cases
      in Japan show a T-cell phenotype. Mycosis fungoides and Sezary syndrome are
      common T-cell lymphomas of the skin. The tumor cells of mycosis fungoides, small
      and medium-sized cells with cerebriform nuclei, are detected in an epidermo-dermo
      junction. The tumor cells show CD3, CD4 and CLA, (cutaneous lymphocyte associated
      antigen) positivity. Various forms of topical therapy, such as topical steroid,
      photochemotherapy (PUVA), and interferons, have been indicated for the good-risk
      group (stages I A, I B and II A). Electron-beam irradiation, various
      chemotherapy, such as low-dose etoposide, low-dose MTX and CPT-11 and deoxy
      coformycin (DCF) plus IFNs, have been indicated for intermediate-risk group
      (stage II B, III and IV A). BRMs plus low-dose etoposide, electron-beam
      irradiation and a multiagent combination chemotherapy, such as MACOP-B, M-BACOD
      or ProMACE-CytaBOM, have been indicated for the high-risk group (stages IV A and
      IV B). Cutaneous B cell lymphoma (CBCL) can be diagnosed using a molecular
      biological assay. The tumor cells of CBCL do not express T-cell antigens such as
      CD2, CD3 and CD43 and show B-cell antigens such as sIg, CD19, CD20 and CD22.
      Electron-beam irradiation has been indicated for early-stage CBCL (stages I and
      II). An effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD
      or ProMACE-CytaBOM, is required for patients with advanced stage CBCL (stages III
      and IV).

PMID- 9020942
TI  - [Chemotherapy for advanced adenocarcinoma of the skin: experience with
      combination chemotherapy and a review of the literature].
AB  - Sweat gland carcinomas are rare malignant tumors of the skin, in addition, the
      diagnosis of primary sweat gland carcinoma is often difficult. Primary treatment
      consists of wide surgical excision with regional lymph node dissection, and the
      tumor is generally not radiosensitive. It has a potential for rapid growth and
      metastasis. Distant metastasis of sweat gland carcinomas is reputed to have a
      very poor prognosis because of the chemo-resistance. Most trials of chemotherapy
      have failed. Numerous single agents have been investigated in this disease, but
      in only one case did 5-fluorouracil result in complete response. Experience with
      combination chemotherapy in metastatic disease is limited; only several complete
      responses and partial responses were reported. In the literature, we found
      reports on several cases of sweat gland carcinoma with overt disease, which had
      been treated with different chemotherapeutic agents in various combinations.
      These studies have suggested the combined use of doxorubicin, cyclophosphamide,
      mitomycin C, vincristine, cisplatin, 5-fluorouracil, bleomycin and melpharan.
      Advanced extramammary Paget's disease is also adenocarcinoma of the skin. The
      recommended treatment for localized extramammary Paget's disease is wide margin
      resection. The role of therapy in advanced unresectable extramammary Paget's
      disease is unestablished. A review systemic chemotherapy of extramammary Paget's
      disease in the literature revealed a few complete responses and partial
      responses. We tried a new drug combination consisting of epirubicin, mitomycin C.
      vincristine, carbcplatin and 5-fluorouracil for advanced adenocarcinoma of the
      skin. Our two patients had excellent responses to this new regimen.

PMID- 9020943
TI  - [Efficiency of segmental SMANCS/Lip-TAE for hepatocellular carcinoma--comparative
      studies in the efficacy of segmental SMANCS/Lip-TAI].
AB  - We compared the segmental SMANCS/Lip-TAI and the segmental SMANCS/Lip-TAE and
      studied the effectiveness of both treatments and the influence and/or the side
      effects on liver function. In resected cases, we studied histopathologic
      examination. The response rate of the group treated by TAI was 28.6%, and that of
      the group treated by TAE was 76.5%. In the group treated by TAE, the therapeutic
      effects were good in nodular type HCC, using small doses of SMANCS. In both
      groups, the incidence and degree of side effects showed no significant
      difference. Hepatic insufficiency occurred in a few cases of the group treated by
      TAI. In resected cases, viable areas remained below the tumor capsule. In
      conclusion, segmental SMANCS/Lip-TAE seemed to be an effective treatment without
      any serious complications.

PMID- 9020944
TI  - [Evaluation of combination chemotherapy with 5-FU and CDDP for human gastric
      carcinoma transplanted into nude mice].
AB  - Combined chemotherapy of 5-FU and CDDP is useful for advanced or recurrent
      gastric cancer. To evaluate the efficacy of this chemotherapy, using human
      gastric carcinoma (NSC-30) maintained in the subcutaneous (sc) space in nude
      mice, we designed the following four experimental groups: 1) control group, 2) 5
      FU group, 3) CDDP group, and 4) combined therapy group of 5-FU and CDDP (FP
      group). 5-FU (150 mg/kg) was injected into the intraperitoneal space for seven
      days using AlZet osmotic pumps. CDDP (9 mg/kg) was injected into the
      intraperitoneal space at one time. The tumor growth of drug administered groups
      was inhibited compared with the control group, especially in the FP group. Body
      weight and general condition of nude mice did not differ between groups. We also
      measured tumor concentrations of 5-FU and thymidylate synthetase (TS) total,
      free, inhibition rate between 5-FU group and FP group. The tumor 5-FU
      concentration of FP group was slightly higher than in 5-FU group, but the TS
      inhibition rate was almost the same. In conclusion, this combined therapy using
      Alzet osmotic pump is a useful drug sensitivity test as a conventional system.

PMID- 9020945
TI  - [Granisetron versus granisetron plus methylprednisolone in the prevention of
      chemotherapy induced nausea and vomiting--in adjuvant chemotherapy, including
      CDDP against gastric cancer].
AB  - CDDP is one of the most effective drugs in chemotherapy for gastric cancer. We
      compared the antiemetic effect of a combination of granisetron and
      methylprednisolone with that of granisetron administered alone. Twenty
      postgastrectomy-patients who were to receive moderately emetogenic chemotherapy,
      including CDDP, were enrolled in randomized fashion to evaluate the efficacy and
      toxicity of two antiemetic regimens. The following antiemetic regimens were used:
      3 mg of granisetron given intravenously before chemotherapy (11 patients) or a
      combination of granisetron and 250 mg of methylprednisolone in the same manner (9
      patients). Granisetron combined with methylprednisolone tender to be more
      effective than granisetron alone. The adverse effects were very mild. Their
      efficacy against delayed emesis is still not entirely satisfactory.

PMID- 9020946
TI  - [Low-dose cisplatin added to continuous infusion of 5-fluorouracil or oral
      administration of UFT for inoperable advanced or recurrent colorectal cancer].
AB  - Combined chemotherapy with 5-FU or UFT and CDDP was performed in 22 cases with
      inoperable advanced or recurrent colorectal cancer. When in hospital, 5-FU 375
      mg/m2/day c.i.v.. (days 1-7) and CDDP 3.75 or 7.5 mg/m2/day i.v.. (days 1-5) were
      administered for as many weeks as possible, while for outpatients UFT 450
      mg/m2/day po (days 1-7) and CDDP 3.75 or 7.5 mg/m2/day div. (days 2 and 5 were
      given for as many weeks as possible. The performance status (PS) of the cases at
      the beginning of the chemotherapy was lower than 3 in 15 patients and over 3 in 7
      patients. The response rate in cases with no history of systemic 5-FU
      chemotherapy was 30%, and the mean NC period in all cases of NC was 170 days.
      Half of the symptoms were improved in cases with some symptoms before
      chemotherapy, and half of the patients whose PS was over 3 could leave the
      hospital after chemotherapy. Toxicity was seen in 80% of the cases, but those
      over grade 3 were seen in only 2 cases. The mean administration period of the
      chemotherapy was 180 days, which shows a high compliance of the method.

PMID- 9020947
TI  - [Usefulness of THP-COPBLM therapy in elderly patients with non-Hodgkin's
      lymphoma].
AB  - We studied the remission rate and adverse effects in THP-COPBLM therapy
      consisting of pirarubicin (THP), which is said to be less cardiotoxic than
      doxorubicin. Subjects were 21 non-Hodgkin's lymphoma (NHL) patients older than 70
      years of age. Of 21 patients, complete remission (CR) was achieved in 16 patients
      (76.2%) and partial remission in 2 patients (9.5%). Classified by stages, CR was
      achieved in 5 out of 6 patients in stage II, 7 out of 8 in stage III and 4 out of
      7 in stage IV. Two-year survival rate was 61.5%. Adverse effects were observed in
      7 patients (33.3%) with grade 3 or above leukocytopenia, 2 (9.5%) with
      thrombocytopenia and 1 (4.8%) with gastrointestinal symptoms. However, no
      abnormality in EKG was found, and the left ventricular ejection fraction in
      echocardiography did not differ before and after therapy. One patient each
      developed pneumonia and sepsis when they had granulocytopenia. THP-COPBLM therapy
      seemed useful in treatment of elderly patients with NHL. There were few adverse
      effects such as gastrointestinal symptoms or cardiotoxicity. However,
      leukocytopenia was observed in many patients despite combined use of G-CSF,
      suggesting the dose and administration method of THP should be studied further.

PMID- 9020948
TI  - [Bropirimine (U-54461S) early phase II clinical studies--to investigate the
      efficacy and safety of bropirimine treatment on various malignant tumors
      (urological, hematologic, and dermal cancers)].
AB  - Early Phase II clinical studies with bropirimine (U-54461S) having interferon
      (IFN) inducing and direct antiproliferative activities were conducted in patients
      with various solid tumors or hematologic neoplasm at 34 institutions nationwide.
      To investigate the safety and efficacy of the treatment, bropirimine was orally
      administered to the patients at the dose of 1g every two hours, three times a day
      for three consecutive days with a four day drug-free interval. Among the 65
      patients registered, 60 patients were eligible and 44 patients completed
      bropirimine treatment in accordance with the respective protocols. Complete
      response (CR) was observed in 7 cases, and partial response (PR) was observed in
      4 cases, so the efficacy rate was 25.0% (7 CRs + 4 PRs/44). Classified by target
      tumors, the efficacy rates were 12.9% (6 CRs/14) in bladder CIS, 33.3% 1 CR/3) in
      superficial bladder cancer. 11.1% 1 PR/9) in renal cell carcinoma, and 42.9% (3
      PRs/7) in malignant lymphoma, respectively. Adverse drug reactions frequently
      observed were influenza-like symptoms such as fever (60.0%) and generalized
      malaise (21.7%), gastrointestinal symptoms like anorexia (56.7%) and
      nausea/vomiting (43.3%), and adverse effects on the circulatory system such as
      tachycardia (15.0%) and abnormalities in ECG (11.7%). Most of these symptoms were
      relieved or improved. Abnormalities in laboratory tests observed frequently were
      adverse effects on the liver such as elevations in GPT (33.3%), in GOT (31.7%),
      and in LDH (18.3%) or on the blood system like a decrease in RBC (18.3%),
      leukopenia (26.7%), or neutropenia (25.0%). In conclusion, bropirimine treatment
      proved to be effective for bladder CIS in particular, suggesting that it will be
      promising for use in the treatment of the disease.

PMID- 9020949
TI  - [Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the
      bladder. Japan Bropirimine Study Group].
AB  - Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor
      agent that has interferon inducing and anti-proliferative activities, was
      conducted in patients with bladder CIS at 38 institutions nationwide. To
      investigate the efficacy and safety of the treatment, bropirimine was
      administered to the patients at the dose of 750 mg every two hours, three times a
      day, for three consecutive days with four-day drug withdrawal, based on the
      results of the preceding clinical studies up to early phase II. Among the 48
      patients registered, 41 patients were evaluable for antitumor efficacy. Complete
      response (CR) was observed in 17 of them, no change (NC) in 18 patients, and
      progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%.
      Classified by patient background, the efficacy rates were 58.3% (7/12) in
      patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder
      CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously
      given chemotherapeutic agents or BCG by intravesical or other routes. Adverse
      drug reactions frequently observed were influenza-like symptoms such as fever and
      generalized malaise and gastrointestinal symptoms like anorexia and
      nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in
      laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia
      were observed. These adverse effects were all tolerated by the patients. From the
      above results, bropirimine was considered to be a useful oral agent for the
      treatment of bladder CIS.

PMID- 9020950
TI  - [Intracellular distribution of bovine serum albumin-conjugated doxorubicin and
      multidrug resistance].
AB  - The intracellular distribution of bovine serum albumin (BSA)-conjugated [14C]
      doxorubicin (DXR) was investigated in a rat hepatoma cell line (AH66P) and its
      anthracycline resistant subline (AH66DR). After the conjugate had been taken up
      into the cells by endocytosis and degraded in the lysomes, active adducts with a
      molecular mass of approximately 2 kDa were distributed to target organellae such
      as nuclei and mitochondria. Drug accumulation in the nuclear fraction was lower
      in AH66DR cells than in AH66P cells, but the level of drug radioactivity in the
      DNA fraction, which was extracted from the same nuclear fraction, was higher in
      the AH66DR cells than in AH66P cells. It is presumed from these results that the
      intercalated level of the drug into DNA was sufficient to exhibit cytotoxicity
      against AH66DR cells as well as AH66P cells. A part of the active adducts was
      effluxed from AH66DR cells by P glycoprotein (Pgp) in the same manner as DXR
      because the efflux of the adducts was suppressed by verapamil, an inhibitor of
      Pgp. The IC50 values of BSA DXR conjugate was decreased from 120 nM to 2 nM for
      AH66DR cells and from 3 nM to 0.6 nM for AH66P cells by the co-treatment with 5/M
      verapamil, respectively.

PMID- 9020952
TI  - [A case of recurrent gallbladder cancer with marked response to arterial infusion
      chemotherapy and transarterial embolization].
AB  - A 50-year-old man with gallbladder cancer was treated by extended cholecystectomy
      and regional lymph node dissection. At 13 months after surgery, CEA showed high
      serum levels, and an enlarged liver tumor due to recurrence was demonstrated by
      computed tomography. After arterial infusion chemotherapy consisting of CDDP,
      epirubicin and 5-FU, the tumor size and serum level of CEA were significantly
      decreased. After this therapy and transcatheter arterial embolization, the liver
      tumor markedly responded and became undetectable. It was suggested that this
      therapy was effective for gallbladder cancer.

PMID- 9020951
TI  - [A case of lung adenocarcinoma associated with remarkably high levels of CA 19-9
      and lymphangitis carcinomatosa].
AB  - A 69-year-old male was admitted to our hospital because of dry cough. Chest X-P
      and CT scans showed a mass shadow in the right lung, thickening of pulmonary
      vessels and pleural effusion. Cytological examination of transbronchial brushing
      specimen revealed lung adenocarcinoma. Cancer cells were also detected in pleural
      effusion. High levels of CA 19.9 were noticed: 48,400 U/ml in serum and 395,000
      U/ml in pleural effusion, respectively. Two courses of combined chemotherapy
      (CDDP + VDS) were done. Concurrent chest radiation therapy (40 Gy) to primary
      tumor was also performed. After treatment the primary tumor decreased in size on
      CT scan analysis, but the patient suffered from respiratory failure due to the
      increase of sputa and pleural effusion and died 104 days after admission.

PMID- 9020953
TI  - [A case of advanced gastric cancer that responded to long-term administration of
      low-dose 5'-DFUR].
AB  - A 83-year-old female suffering from advanced gastric cancer with paraaortic lymph
      node metastases was administered low-dose 5'-DFUR (600 mg/day) orally. The
      primary tumor reduced in size fifty days after the start of the treatment, and
      the swelled lymph node disappeared on abdominal CT scan. Specimens obtained by
      endoscopical biopsy were highly susceptible to pathological degeneration of the
      cancer. Low-dose 5'-DFUR was effective both for the primary lesion of gastric
      cancer and for the lymph node metastases in this case.

PMID- 9020954
TI  - [A case of gastric malignant lymphoma with perforation during chemotherapy].
AB  - A 54-year-old male was admitted for loss of appetite lasting for about 3 months.
      The patient was diagnosed as malignant lymphoma in the stomach invading directly
      the pancreas, spleen and transverse colon. Chemotherapy, two cycles of VEPA.M,
      was selected as the initial treatment. After the first cycle of chemotherapy, the
      patient was discharged temporarily. During the second cycle, on an ambulant
      basis, the patient suddenly complained of severe pain and distension in the
      abdomen. Through the X-ray examination of the chest, free air was demonstrated in
      the bilateral subphrenic spaces. The patient was diagnosed as perforation of the
      gastrointestinal tract. Subsequently, total gastrectomy was performed.
      Pathological examination revealed no malignant cells in the stomach wall. It is
      suggested that the perforation was caused by weakening of the stomach wall
      following chemotherapy.

PMID- 9020955
TI  - [A case of colon cancer with local recurrence successfully treated by systemic
      and local intra-arterial chemotherapy using a combination of 5-fluorouracil,
      interferon-alpha 2A, leucovorin and carboplatin].
AB  - A 59-year-old man with colon cancer was diagnosed as having a local recurrence of
      the disease, forming a huge intra pelvic tumor, accompanied by pulmonary
      metastasis 16 months after hemicolectomy. He received alternate systemic and
      local chemotherapy consisting respectively of a 5-day course of continuous
      infusion of 5-FU 600 mg/m2/day, bolus injection of leucovorin (LV) 20 mg/m2/day,
      intramuscular injection of interferon (IFN)-alpha 2a 6 x 10(6) IU/day, and intra
      arterial administration of 5-FU, LV and carboplatin using reservoir catheter
      through pudendal artery, each repeated every 3 weeks. After 6 systemic and 8
      local treatments, metastatic lesions disappeared and the intra-pelvic tumor
      shrunk by 62%, indicating a partial response. The patient then underwent
      dissection of the intra-pelvic tumor. Pathological examination indicated a
      curative resection. Alternate systemic and local intra arterial chemotherapy
      using a combination of 5-FU, LV, IFN and and carboplatin is highly promising for
      metastatic colorectal cancer with local recurrence.

PMID- 9020956
TI  - [Study of anti-cancer drug delivery into the organs during resection of esophagus
      -an experimental study].

PMID- 9020957
TI  - [Chromosome copy number of a colon cancer cell line determined by two color
      fluorescence in situ hybridization].

PMID- 9020958
TI  - Review: proximity effects in the production of chromosome aberrations by ionizing
      radiation.
AB  - After ionizing radiation has induced double-strand DNA breaks (dsb), misrejoining
      produces chromosome aberrations. Aberration yields are influenced by "proximity'
      effects, i.e., by the dependence of misrejoining probabilities on initial dsb
      separations. We survey proximity effects, emphasizing implications for chromosome
      aberration-formation mechanisms, for chromatin geometry, and for dose-response
      relations. Evidence for proximity effects comes from observed biases for centric
      rings and against three-way interchanges, relative to dicentrics or
      translocations. Other evidence comes from the way aberration yields depend on
      radiation dose and quality, tightly bunched ionizations being relatively
      effective. We concludes (1) that misrejoining probabilities decrease as the
      distance between dsb at the time of their formation increases, and almost all
      misrejoining occurs among dsb initially separated by < 1/3 of a cell nucleus
      diameter; (2) that chromosomes occupy (irregular) territories during the G0/G1
      phase of the cell cycle, having dimensions also roughly 1/3 of a cell nucleus
      diameter, (3) that proximity effects have the potential to probe how much
      different chromosomes intertwine on move relative to each other: and (4) that
      incorporation of proximity effects into the classic random breakage-and-reunion
      model allows quantitative interrelation of yields for many different aberration
      types and of data obtained with various FISH painting methods or whole-genome
      scoring.

PMID- 9020959
TI  - Investigating the nature of chromatid breaks produced by restriction
      endonucleases.
AB  - It is a basic assumption of the breakage-and-reunion theory that the majority of
      open chromatid breaks seen at metaphase are the residue of unrejoined primary
      breaks that have neither restituted nor rejoined illegitimately to form exchange
      aberrations. If Chinese hamster chromosomes with BrdU sister-chromatid
      differentiation are irradiated, and chromatid aberrations scored from G2 cells,
      some 15-20% of open breaks show a colour-jump at the point of discontinuity,
      indicating a two-lesion intrachange origin. Since we see complete forms of
      several intrachanges whose incomplete forms will also look like breaks, but
      devoid of a colour-jump, it appears that a substantial proportion of observed
      breaks are intrachange derived. Experiments to date show that the colour-jump
      proportion is constant, irrespective of radiation dose, radiation quality, BrdU
      concentration and hamster cell origin. It is the same for the very low
      "spontaneous' breaks found in control samples. Restriction endonucleases (RE) can
      be introduced into cells by various poration methods, and are highly efficient at
      producing all types of aberrations. This is taken as strong evidence that DNA dsb
      are significant lesions triggering aberrations. One might anticipate, therefore,
      that observed breaks will be predominantly unrejoined dsb, and the proportion of
      colour-jump break correspondingly low. We tested this supposition using three RE;
      Alu 1, a blunt-end cutter, Sau3A 1, a cohesive-end cutter, both with a short life
      time in vivo, and Mbo 1, an isoschizomer of Sau3A 1, which has a long cutting
      life-time in vivo. Although there were differences in absolute yields of breaks,
      and of relative frequencies of aberration types recovered, the proportion of
      colour-jump breaks was as high as that in a parallel X-ray experiment, and fell
      well within the range encountered in all our previous experiments. It is
      difficult to reconcile this universal constancy of colour-jump breaks with the
      expectations of breakage-and-reunion theory, where the occurrence of two-break
      events must be a treatment variable. Rather, our results suggest that most open
      breaks are secondary, resulting from a regular intrachange processing mechanism.

PMID- 9020960
TI  - A rapid method for measuring pericentric inversions using fluorescence in situ
      hybridization (FISH).
AB  - We used three common fluorescent probes to measure pericentric inversion
      frequencies in 2.9 Gy 60Co gamma-irradiated human lymphocytes. For a given
      chromosome, the first probe is specific to one telomeric region, the second probe
      is specific to one subcentromeric region and the third probe is specific to the
      centromere. A pericentric inversion is made observable by the change in position
      (switching) of the fluorescent signals relative to the chromosome centromere. Our
      data showed equality between pericentric inversions and centric rings. The
      calculated whole-genome F-ratio of apparently simple translocations to
      pericentric inversions was 5.6.

PMID- 9020961
TI  - Estimation of minimal size of translocated chromosome segments detectable by
      fluorescence in situ hybridization.
AB  - Apparent non-reciprocal translocations are commonly observed using fluorescence
      in situ hybridization. We hypothesize that these are 'hidden' reciprocals due to
      one translocated segment being too small to detect. Assuming that the
      translocation breakpoints distribute randomly, the proportion of reciprocal to
      non-reciprocal exchanges can be used to estimate the minimal detectable size of
      translocated segments. To estimate segment size in this study, cytogenetic data
      for 120 A-bomb survivors were used. Among 2295 aberrant metaphases, 1629
      exhibited reciprocal translocations and 666 non-reciprocal. Of the non-reciprocal
      translocations, 501 showed only a painted chromosome segment, translocated to an
      unpainted chromosome with centromere, and 165 showed only an unpainted chromosome
      segment, translocated to a painted chromosome with centromere. On the basis of
      the above two assumptions, we obtained the most likely estimates for minimal
      detectable sizes: 11.1 +/- 0.8 Mb for the painted and 14.6 +/- 0.6 Mb for the
      unpainted chromosomes. The implications of these findings are discussed.

PMID- 9020962
TI  - Chromosomal sensitivity to clastogenic agents and cell cycle perturbations in
      Nijmegen breakage syndrome lymphoblastoid cell lines.
AB  - The relationship between chromosomal breakage and perturbations of cell cycle
      progression was investigated in lymphoblastoid cell lines established from a
      healthy donor, two subjects affected by Nijmegen Breakage Syndrome (NBS) and an
      ataxia-telangiectasia (AT) patient. The cytogenetic analysis revealed a similar
      chromosomal hypersensitivity in both NBS and AT cells exposed in the G1 phase to
      200 cGy X-rays or in G2 to 15-30 cGy. Similarly, no differences were observed in
      the frequency of chromatid-type aberrations induced in G2 by 1-2 pg/ml
      calicheamicin gamma 1I, a DNA double-strand break inducer. In addition, as
      observed in AT cells, the rate of G2 radiation-induced chromosomal damage was
      less enhanced in NBS than in control cells following 3-h incubation with
      inhibitors of DNA synthesis/repair (cytosine arabinoside, aphidicolin, DMSO,
      hydroxyurea, caffeine). This is suggestive of an altered DNA lesion-processing
      pathway common to both syndromes. Despite the close resemblance of cellular
      phenotypes in the two syndromes, the analysis of mitotic indices carried out at 2
      and 4 h postirradiation indicated that NBS sustained a G2-delay greater than that
      observed in AT cells, Furthermore, the flow cytometric analysis of 50-300 cGy
      irradiated cells at 10 and 20 h before harvesting showed that NBS cells sustained
      a G2/M phase arrest markedly lower than AT cells. Our data indicate that NBS and
      AT gene products are involved in a common pathway of radiation-induced
      chromosomal damage, but in a different one for cell cycle control after
      irradiation.

PMID- 9020963
TI  - Unstable and stable chromosomal aberrations in lymphocytes of people exposed to
      Chernobyl fallout in Bryansk, Russia.
AB  - Analyses of unstable and stable chromosomal aberrations in peripheral blood
      lymphocytes were used in the assessment of radiation exposure of residents of a
      village situated in the Chernobyl fallout-contamination zone of Bryansk, Russia.
      Blood samples were taken from subjects residing in villages with high (> 1100
      kBq/m2 137 Cs; Mirnyi) and very low (< 37 kBq/m2 137 Cs; Krasnyi Rog)
      contamination, 7 years after the Chernobyl accident. The groups were matched by
      age, sex, smoking habits and previous medical radiological exposures. A total of
      200 people (100 exposed, 100 controls) were analysed for the presence of unstable
      aberrations from Giemsa-stained slides. To study stable aberrations, chromosome
      painting analyses were performed on 100 subjects (50 exposed, 50 controls), using
      painting probes for chromosomes 1, 2 and 4 and a pancentromeric probe. People
      living in the contaminated area showed significantly higher rates of unstable
      chromosome-type aberrations but not chromatid-type aberrations in their
      lymphocytes, indicating radiation exposure as a causative factor for the observed
      difference. No significant differences were found in the aberration rates between
      the two areas by the chromosome painting method. The levels of chromosome
      exchanges were low in both populations, but consistently higher in Mirnyi
      compared with the control area. The magnitude of radiation exposure resulting
      from Chernobyl fallout was estimated on the basis of excess stable chromosomal
      aberrations in the lymphocytes of the Mirnyi population compared with the
      controls.

PMID- 9020964
TI  - In vitro micronucleus-centromere assay to detect radiation-damage induced by low
      doses in human lymphocytes.
AB  - One of the major drawbacks of the in vitro micronucleus (MN) assay for human
      lymphocytes is its reduced sensitivity for the detection of damage induced by low
      radiation doses, due to the high variability among the spontaneous MN
      frequencies. In this paper we investigated the enhancement of the sensitivity of
      the MN assay by analysing spontaneous and radiation-induced MN for the presence
      of centromeres. For this, in situ hybridization (FISH) with the human
      pancentromeric DNA probe, p82H, was performed. Our results revealed that a high
      percentage (73%) of the spontaneous MN contain a centromere. These centromere
      positive MN indicate the presence of a whole chromosome/chromatid. After in vitro
      irradiation with low doses (0.1-2 Gy) 60Co gamma-rays mainly centromere-negative
      MN were induced while only a very small number of additional centromere-positive
      MN were formed. This demonstrates that radiation-induced MN mainly contain
      acentric fragments pointing to the clastogenic action of ionizing radiation.
      Furthermore, our data show that the sensitivity of the MN assay for low dose
      detection is increased by scoring only centromere-negative MN.

PMID- 9020965
TI  - Radon daughter deposition on surfaces carrying alternating electric fields.
AB  - A theoretical model is proposed to explain the radon daughter deposition
      enhancements on surfaces subject to power frequency AC fields, recently reported
      by Henshaw et al. (1996). The effect of oscillatory contacts with the surface
      combined with turbulent diffusion is investigated within the framework of the
      convective-diffusion equation, through an approximation of the dividing surface.
      The fine and the course activity fractions are treated separately for flat-plate
      and wire-plane configurations. The results indicate maximum enhancement factors
      for 218Po in the range 1.7-3.3 for flat-plate and 5.2-15.5 for wire-plane
      configurations under typical indoor environmental conditions. While these compare
      favourably with the corresponding observed values, further analysis appears
      necessary to explain the greater enhancements observed in the case of 214Po.

PMID- 9020966
TI  - Mutation induction by high-density, 50-Hz magnetic fields in human MeWo cells
      exposed in the DNA synthesis phase.
AB  - Exposure of cultured human MeWo cells to high-density (400 mT at 50 Hz) extremely
      low frequency magnetic fields (ELF-MF) induced mutations in the hypoxanthine
      guanine phosphoribosyl transferase gene. Mutation induced by the ELF-MF increased
      during the DNA-synthesis phase in synchronously growing cells. DNA replication
      errors and/or disturbance of the mismatch repair systems caused by exposure to
      ELF-MF may be involved in the mutagenic effect.

PMID- 9020967
TI  - A new immunobiological view of radiation-promoted lymphomagenesis.
AB  - Whole-body irradiation produces T-cell leukaemias/ lymphomas (TCL) in some
      strains of inbred mice in an X-ray dose-related manner. Radiation biologists have
      related the rapid "initiation' and early appearance of preleukaemic cells in
      these mice to unrepaired DNA damage inflicted by radiation. Following initiation,
      radiation-altered thymic differentiation fosters multi-step transformation
      changes in proto-oncogenes and suppressor gene expression in individual clones of
      non-invasive preleukaemia cells as they progress to malignancy. The malignant
      clones arising from small numbers of initiated preleukaemia thymocytes become
      fully transformed only after several more months to a year after irradiation in
      those strains of mice which develop T-cell lymphomas. When the RFM mouse was
      subjected to sublethal whole-body X-ray, only 50% of the mice developed TCL by 6
      months, yet nearly all developed preleukaemia thymocytes. The T-cell-mediated
      immune response of the irradiated host has never been substantiated to contribute
      to malignant TCL development. Until recently, X-ray-induced TCL were not known to
      carry common tumour rejection antigens TATA. However, several studies have
      revealed that both preleukaemia cells and fully malignant TCL express an
      immunogenic, common oncofoetal glycoprotein, termed 44kD OFA. OFA-activated
      memory CD4 Tm and CD8 Ten. T-effector cells in irradiated mice expressing OFA. As
      most irradiated RFM mice exhibit preleukaemia thymocytes yet only half develop
      tumours, this finding implicates active host T-cell effector responses in X-ray
      initiated tumorigenesis. Further, the recent discovery of OFA-specific CD8 Ts
      clones in irradiated mice, which inhibited cytotoxicity of CD8 clones to OFA or
      TSTA, may explain which mice develop T-cell lymphomas.

PMID- 9020968
TI  - Comparative measurements of radiation-induced DNA double-strand breaks by graded
      voltage and pulsed-field gel electrophoresis.
AB  - We compared the ability of graded-voltage gel electrophoresis (GVGE) and pulsed
      field gel electrophoresis (PFGE), to resolve DNA containing double-strand breaks
      (dsb) induced in human MS751 cells after exposure to gamma-radiation. For
      quantitation, prelabelling of the cells with [2-14C]-thymidine prior to
      electrophoresis and subsequent scintillation counting of excised bands was found
      to give closely similar results to Southern blotting and radiolabelled probe
      hybridization followed by phosphorimager quantitation. Compared with PFGE, DNA
      subjected to GVGE migrated further and generated distinct DNA bands. Dsb were
      detected and quantifiable with GVGE at much lower doses than with PFGE the
      radiation dose limits were approximately 2 and 10 Gy respectively. At all doses
      used, the amounts of dsb detected by GVGF, were higher than those by PFGE. GVGE
      coupled with Southern hybridization and phosphorimager analysis is thus a more
      sensitive approach to assessing dsb and their relationship with radiation
      sensitivity. The approach is also convenient when processing large numbers of
      samples and has the additional advantage of avoiding cell prelabelling such as in
      the case of cells extracted directly from human tumour biopsies and normal
      tissues.

PMID- 9020970
TI  - Influence of low doses of gamma-irradiation on mouse skin collagen fibrils.
AB  - The structure of mouse skin collagen fibrils after treatment with 0.5, 1 and 2.5
      Gy gamma-irradiation was studied by electron microscopy. Animals were sacrificed
      1, 4 and 8 weeks after irradiation. Although there were areas where the normal
      parallel packing of fibrils was retained in some regions packing was interrupted
      by abnormal fibrils and in some cases helical twisting was apparent. Irradiated
      collagen fibrils had a lower mean diameter compared with normal and a large
      variability in width. The diameter of 0.5 Gy irradiated fibrils returned to
      normal by 4 or 8 weeks after irradiation. Clusters of abnormal fibrils were found
      when viewed in cross-sections. Their number and size was reversibly dependent on
      the dose level. All fibrils retained normal banding periodicity. Computer
      analysis of irradiated and control patterns led to the conclusion that 0.5-2.5 Gy
      gamma-irradiation had no considerable effect in modifying the charge distribution
      along the mouse skin collagen fibril.

PMID- 9020969
TI  - AM218, a new polyanionic polysaccharide, induces radioprotection in mice when
      administered shortly before irradiation.
AB  - We have shown that the polyanionic polysaccharide AM218 improves the survival
      rate of the potentially lethally irradiated mice. This radioprotective effect was
      highly dependent on the administration schedule, the most efficient protocol
      being that in which the drug was given shortly before irradiation. The
      haematopoietic implications in the pharmacological action of AM218 were confirmed
      by the improved recovery in the three peripheral blood lineages observed in the
      AM218-treated mice. However, because of a marked increase observed in the number
      of white blood cells during the period of highest mortality of the control
      irradiated mice, effects on the neutrophil lineage may account for the effects
      mediated by AM218 in the irradiated mice. Both in vitro and in vivo treatment
      with AM218 before irradiation improved the survival rate of CFU-GM progenitors,
      while no effects were observed on the CFU-S pool. This led us to postulate that
      the improved survival rate of the committed progenitors, at least the granulocyte
      macrophage progenitors, accounts for the radioprotective capacity of AM218.

PMID- 9020971
TI  - Electron microscopy of assembly intermediates of the snRNP core: morphological
      similarities between the RNA-free (E.F.G) protein heteromer and the intact snRNP
      core.
AB  - All four spliceosomal small nuclear ribonucleoproteins (snRNPs) U1, U2, U4/U6 and
      U5 contain a common structural element called the snRNP core. This core is
      assembled from the common snRNP proteins and the small nuclear RNA (snRNA). We
      have used electron microscopy to study the structure of two intermediates of the
      snRNP core assembly pathway: (1) the (E.F.G) protein complex, which contains only
      the smallest common proteins E, F and G; and (2) the subscore of U5 snRNP, in
      which the U5 RNA and the common proteins D1 and D2 are bound to the (E.F.G)
      protein complex. The general structure of the subscore was found to resemble that
      of the complete snRNP core, which contains the components of the subscore plus
      the common proteins B/B' and D3. Both the complete snRNP core and subscore
      particles are globular, with diameters of 7 to 8 nm. They show a characteristic
      accumulation of stain at the centre. However, some subscore images showed nicked
      outlines not seen with the complete snRNP cores. The (E.F.G) protein complex
      appeared as a ring, with an outer diameter of about 7 nm and a central hole 2 nm
      across. The molecular dimensions of the E, F and G proteins imply that the
      thickness of the (E.F.G) ring structure is only about 2 nm. Comparison of the
      (E.F.G) structure complex with the snRNP core and subcore structures implicates
      that a flat side of the ring-shaped (E.F.G) complex provides the assembly site(s)
      for the other components of the snRNP during core assembly: first for the D1 and
      D2 proteins (and probably the snRNA) during subscore formation, and then for the
      B/B' and D3 proteins in the completion of the snRNP core particle.

PMID- 9020972
TI  - Polyadenylation creates the discriminator nucleotide of chicken mitochondrial
      tRNA(Tyr).
AB  - In the chicken mitochondrial genome, the gene for tRNA(Tyr) overlaps by one
      nucleotide with the downstream tRNA(Cys) gene, which is located on the same
      strand. The overlapping nucleotide, a guanosine residue, thus encodes both the
      discriminator base of the tRNA(Tyr) and the 5'base of the tRNA(Cys). When cDNA
      clones of circularized forms of the tRNA(Tyr) are analyzed, the discriminator
      nucleotide is an adenosine residue rather than the genomically encoded guanosine.
      Thus, the tRNA(Tyr) is subjected to an RNA editing activity similar to that shown
      to exist in the mitochondria of two other animal species. Interestingly, some
      cDNA clones have several adenosine residues at their 3'-ends instead of the
      expected CCA-sequence. Furthermore, a review of sequence data from animal
      mitochondrial genomes suggests that only tRNAs whose discriminator bases are
      adenosines tend to have genes that overlap with downstream genes. Thus,
      polyadenylation seems to be a major component of the RNA editing machinery that
      affects overlapping genes in animal mitochondria.

PMID- 9020973
TI  - Direct visualization of extensibility in isolated titin molecules.
AB  - "Molecular combing" induced by a receding meniscus has been shown to extend
      individual titin molecules. Electron microscopy reveals that both ends of the
      molecule tend to attach to a mica substrate, probably due to their local positive
      charges. This leaves the remainder of the molecule free to be straightened and
      extended by forces of up to approximately 800 pN. A small region in the I-band
      part of the molecule, which probably corresponds to sequence high in P, E, V and
      K residues, is the most compliant and appears to extend by an unfolding of the
      polypeptide chain. Other parts of the molecule are also capable of extension.
      These mechanical extensions in titin are probably reversible.

PMID- 9020974
TI  - Two-dimensional crystallization of the light-harvesting I-reaction centre
      photounit from Rhodospirillum rubrum.
AB  - A stoichiometric unit of the light-harvesting complex I and the reaction centre
      (LHI-RC complex) has been isolated from a carotenoid-less mutant of the purple
      non-sulphur bacterium Rhodospirillum rubrum by mild solubilization of
      photosynthetic membranes with the phospholipid detergent
      diheptylphosphatidylcholine. Dialysis of the isolated LHI-RC complexes in the
      presence of added dioleoyl-sn-phosphatidylcholine produced ordered two
      dimensional crystals. Digital image processing revealed that the LHI-RC are
      packed together in a square lattice (a = b = 16.3 nm). The dimensions of the LHI
      ring are essentially identical with those determined from two-dimensional (2D)
      crystals of purified carotenoid-containing light-harvesting I complexes after
      analysis by cryo-electron microscopic techniques or from negatively stained 2D
      crystals of purified LHI complexes from a carotenoid-less mutant. Each LHI ring
      of the LHI-RC complex contains a central diffuse stain-excluding region, which is
      assigned to the reaction centre. The analysis of the LHI-RC 2D crystals strongly
      suggests that the geometry and subunit stoichiometry of the LHI ring is
      unaffected by the presence of a reaction centre that can probably assume various
      orientations within the ring.

PMID- 9020975
TI  - Acceleration of the folding of hen lysozyme by trifluoroethanol.
AB  - The refolding of a partially structured state of hen lysozyme formed in 60% (v/v)
      2,2,2-trifluoroethanol (TFE) has been studied using hydrogen exchange pulse
      labelling monitored by 2D 1H NMR, and by stopped flow fluorescence and CD
      measurements. The results are compared with similar studies of the refolding of
      the protein denatured in 6 M guanidine hydrochloride (GuHCl). Two conclusions
      have emerged from these studies. First, provided that the refolding conditions
      are identical, the two denatured states fold with very similar kinetics, despite
      the fact the extensive secondary structure is present in the TFE-denatured state
      but not in the protein denatured in 6 M GuHCl. This arises because of the rapid
      equilibration of structure in the species formed in the initial stage of folding.
      Second, whilst addition of GuHCl to the refolding buffer decreases the rate of
      folding, low concentrations of TFE increase the rate of folding. The result is
      consistent with slow steps in the refolding of lysozyme being associated
      primarily with the reorganisation of hydrophobic interactions rather than of
      hydrogen bonded structure.

PMID- 9020976
TI  - Energetics of nucleophile activation in a protein tyrosine phosphatase.
AB  - The nucleophilic attack by cysteine 12 in the low-molecular-weight protein
      tyrosine phosphatase is believed to be carried out by the thiolate anion form of
      this residue. We here study the energetics of proton transfer between the thiol
      group of cysteine 12 and a substrate phosphate oxygen atom, to examine the
      effects of the enzymic environment on the stability of the thiolate nucleophile.
      This is done by molecular dynamics and free energy perturbation simulations,
      utilizing the empirical valence bond method to describe the potential surface of
      the system. The calculations show that the protein environment significantly
      stabilizes the thiolate ion, thereby setting the stage for the nucleophilic
      attack. We compare these results with those from further simulations of a mutant
      enzyme, and demonstrate the importance of serine 19 in thiolate stabilization.

PMID- 9020977
TI  - Dual regulation of Escherichia coli secA translation by distinct upstream
      elements.
AB  - The regulation of the Escherichia coli secA gene, whose translation is auto
      repressed except when protein secretion becomes limiting, was investigated using
      a combination of genetic and biochemical approaches. Oligonucleotide-directed
      deletion and point mutagenesis was used to show that only the last quarter of the
      upstream gene, geneX, and the geneX-secA intergenic are essential for proper
      regulation. This region previously shown to contain a secretion-responsive
      element contains two predicted helices, helix I and II, the latter of which would
      occlude the secA Shine-Dalgarno sequence. Mutations that destabilized the lower
      portion of helix II increased secA basal expression, reduced auto-repression by
      SecA protein, but retained a normal pattern of derepression of secA expression
      during a protein export block. The introduction of compensatory mutations into
      helix II that were predicted to restore base-pairing restored secA regulation to
      wild-type levels or nearly so, suggesting that this helix does play a role in
      secA auto-regulation in vivo. In contrast, mutations in the lower portion of
      helix I decreased secA basal expression, reduced auto-repression by SecA protein,
      and abolished the responsiveness of secA expression to a protein export block. In
      this latter case introduction of compensatory mutations into helix I that were
      predicted to restore base-pairing did not restore proper secA regulation,
      indicating that specific nucleotides in this region are required for normal secA
      regulation. Primer-extension inhibition (toeprint) analysis with 30 S ribosoma
      subunits, tRNAMet, and a model segment of geneX-secA RNA carrying the relevant
      mutations was used to show that mutations that destabilized helix II increased
      ribosome binding at the secA translation initiation site, while mutations that
      perturbed helix I decreased ribosome binding at this site. Our results suggest
      strongly that there is a system of dual regulation of secA translation, whereby
      helix I serves as an activator element while helix II serves as a repressor
      element.

PMID- 9020978
TI  - Identification of elements on GeneX-secA RNA of Escherichia coli required for
      SecA binding and secA auto-regulation.
AB  - The protein translocation ATPase of Escherichia coli, SecA protein, auto
      regulates its translation by binding to its translation initiation region in
      geneX-secA mRNA. To analyze this regulation further the secondary structure of
      this portion of geneX-secA RNA was investigated utilizing structure-specific
      nucleases and chemical probing approaches. The results of this analysis were
      consistent with the existence of two adjacent helices, helix I and the lower
      portion of helix II, whose function in secA activation and repression,
      respectively, has been demonstrated. Binding of SecA protein to geneX-secA RNA or
      various mutant derivatives of this RNA was studied by measurement of affinity
      constants, RNA footprint analysis, and quantitation of auto-repression in vivo.
      This analysis showed that the SecA-binding site in geneX-secA RNA was remarkably
      large spanning a region of 96 nucleotides including a 3' portion of helix II, the
      secA translation initiation region and distal sequences. From the size of the
      SecA-binding site and the plasticity of its response to mutational alteration, it
      is suggested that SecA protein contains two distinct RNA-binding sites. Finally,
      it was shown that SecA binding was not sufficient to promote auto-regulation and
      that sequences both upstream (helix I) and within the binding site can contribute
      to auto-regulation without affecting SecA-binding affinity.

PMID- 9020979
TI  - Thymidine inhibits the growth-arrest-specific degradation of thymidine kinase
      protein in transfected L fibroblasts.
AB  - The expression of murine thymidine kinase (TK) is strictly dependent on the
      growth state of the cell. Expressing epitope-tagged TK in LTK cells, we have
      previously shown that low TK enzyme levels in G0 cells are in part due to a
      dramatic decrease in TK protein stability. Here we report that thymidine, one of
      the substrates of TK, is able to counteract the growth-arrest-specific decrease
      of TK expression. While TK mRNA levels and TK translation rate are almost
      unaffected by thymidine, the TK protein half-life rose more than sixfold after
      addition of the nucleoside to resting cells. The effect of thymidine is
      reversible and is independent of its presence during the protein synthesis of TK.
      Dideoxythymidine, a specific inhibitor of the TK enzyme activity, also has the
      capacity to increase TK protein levels in G0 cells, indicating that the substrate
      itself exerts the stabilising effect on the TK protein.

PMID- 9020980
TI  - A natural antibody missing a cysteine in VH: consequences for thermodynamic
      stability and folding.
AB  - While the disulfide bridge is highly conserved within the immunoglobulin fold, a
      few antibody variable domains lack one of the essential cysteine residues. In the
      levan binding antibody ABPC48 one of the essential cysteine residues (Cys H92) of
      the heavy chain variable domain is replaced by tyrosine. We expressed scFv
      fragments with the ABPC48 sequence and a mutant in which the VH disulfide bond
      has been restored in Escherichia coli, purified both proteins by antigen affinity
      chromatography and characterized them by equilibrium denaturation. While the
      ABPC48 protein was found to be significantly less stable than an average scFv
      molecule, the restored disulfide increased its stability above that of other,
      unrelated scFv fragments, explaining why it tolerates the disulfide loss.
      Surprisingly, we observed that under some refolding conditions, the unpaired
      cysteine residue of functional scFv of ABPC48 is derivatized by glutathione. It
      is easily accessible to other reagents and thus appears to be solvent-exposed, in
      contrast to the deeply buried disulfide of ordinary variable domains. This
      implies a very unusual conformation of stand b containing the unpaired Cys H22,
      which might be stabilized by interactions with the tyrosine residue in position
      H92.

PMID- 9020981
TI  - Solution structure of the esperamicin A1-DNA complex.
AB  - Esperamicin A1 is an enediyne antibiotic possessing antitumor activity associated
      with its ability to bind and, following activation, affect strand cleavage of
      DNA. We report on the solution structure of the esperamicin A1-d(C-G-G-A-T-C-C-G)
      duplex complex based on a combined analysis of NMR and molecular dynamics
      calculations including intensity refinement in a water box. The refined solution
      structures of the complex provide a molecular explanation of the sequence
      specificity for binding and cleavage by this member of the enediyne family of
      antitumor antibiotics. Esperamicin A1 binds to the DNA minor groove with its
      methoxyacrylyl-anthranilate moiety intercalating into the helix at the (G2-G3)
      (C6'-C7') step. The methoxyacrylyl-anthranilate intercalator and the minor groove
      binding A-B-C+ risaccharide moieties rigidly anchor the enediyne in the minor
      groove such that the pro-radical centers of the enediyne are proximal to their
      anticipated proton abstraction sites. Specifically, the pro-radical C-3 and C-6
      atoms are aligned opposite the abstractable H-5' (pro-S) proton of C6 and the H
      1' proton of C6' on partner strands, respectively, in the complex. The thiomethyl
      sugar B residue is buried deep in an edgewise manner in the minor groove with its
      two faces sandwiched between the walls of the groove. Further, the polarizable
      sulfur atom of the thiomethyl group of sugar B residue is positioned opposite and
      can hydrogen-bond to the exposed amino proton of G3' in the complex. There is
      little perturbation away from a right-handed Watson-Crick base-paired duplex in
      the complex other than unwinding of the helix at the intercalation site and
      widening of the minor groove centered about the enediyne-binding and anthranilate
      intercalation sites. Sequence-specific binding of esperamicin A1 to the d(C-G-G-A
      T-C-C-G) duplex is favored by the complementarity of the fit between the drug and
      the floor of the minor groove, good stacking between the intercalating
      anthranilate ring and flanking purine bases and intermolecular hydrogen-bonding
      interactions.

PMID- 9020982
TI  - Solution structure of the calicheamicin gamma 1I-DNA complex.
AB  - Calicheamicin gamma 1I is an enediyne antibiotic possessing antitumour activity
      associated with its ability to bind and following activation, affect double
      strand cleavage at oligopyrimidine-oligopurine tracts on DNA. Footprinting and
      chemical modification studies have identified the (T-C-C-T).(A-G-G-A) sequence as
      a preferred calicheamicin gamma 1I binding site and established the importance of
      the 5'-guanine residue as critical for high affinity binding. The sequence
      specificity of intermolecular recognition has been identified with the
      aryltetrasaccharide component of the drug together with an important contribution
      from the iodine atom on the thiobenzoate ring to the affinity of complex
      formation. Calicheamicin gamma 1I binds to the minor groove of the DNA duplex and
      in the process positions the enediyne ring to abstract hydrogen atoms from
      partner strands leading to double-strand cleavage. We report on the solution
      structure of the calicheamicin gamma 1I-DNA hairpin duplex complex containing a
      central (T-C-C-T).(A-G-G-A) segment based on a combined analysis of NMR and
      molecular dynamics calculations including intensity refinement in a water box.
      The refined solution structures of the complex provide a molecular explanation of
      the sequence specificity of binding and cleavage by this member of the enediyne
      family of antitumor antibiotics. Calicheamicin gamma 1I binds to the DNA minor
      groove with its aryltetrasaccharide segment in an extended conformation spanning
      the (T-C-C-T).(A-G-G-A) segment of the duplex. Further, the thio sugar B molecule
      and the thiobenzoate ring C molecule are inserted in an edgewise manner deep into
      the minor groove with their faces sandwiched between the walls of the groove. A
      range of intermolecular hydrophobic and hydrogen-bonding interactions account for
      the sequence specific recognition in the complex. These include critical
      intermolecular contacts between the iodine and sulfur atoms of the thiobenzoate
      ring of the drug with the exposed exocyclic amino protons of the 5' and 3'
      guanine bases, respectively, of the A-G-G-A segment on the DNA. The bound
      aryltetrasaccharide in turn positions the enediyne ring deep in the minor groove
      such that the pro-radical carbon centers of the enediyne are proximal to their
      anticipated proton abstraction sites. Specifically, the pro-radical C-3 and C-6
      atoms are aligned opposite the abstractable H-5' (pro-S) and H-4' protons on
      partner strands across the minor groove, respectively, in the complex. The DNA
      duplex is right-handed with Watson-Crick base-pairing in the complex. The helix
      exhibits a B-DNA type minor groove width at the aryltetrasaccharide binding-site
      while there is widening of the groove at the adjacent enediyne binding-site in
      the complex. The DNA helix exhibits localized perturbations at the binding-site
      as reflected in imino proton complexation shifts and specific altered sugar
      pucker geometrics associated with complex formation. Sequence-specific binding of
      calicheamicin gamma 1I to the (T-C-C-T).(A-G-G-A) containing DNA hairpin duplex
      is favored by the complementarity of the fit through hydrophobic and hydrogen
      bonding interactions between the drug and the floor and walls of the minor groove
      of a minimally perturbed DNA helix.

PMID- 9020983
TI  - Crystal structure of calf spleen purine nucleoside phosphorylase in a complex
      with hypoxanthine at 2.15 A resolution.
AB  - Trimeric calf spleen purine nucleoside phosphorylase has been complexed with
      hypoxanthine via phosphorolysis of inosine in the presence of phosphate. The
      resulting, "Michaelis" complex (three hypoxanthine molecules per trimer),
      presumed to be formed under these conditions, crystallized in the cubic space
      group P2(1)3, with unit cell dimension a = 94.11 A and one monomer in the
      asymmetric crystal unit; the biologically active trimer is located on the
      crystallographic 3-fold axis. High-resolution X-ray diffraction data were
      collected using synchrotron radiation (EMBL outstation, Hamburg, c/o DESY). The
      crystal structure has been determined by molecular replacement and refined at
      2.15 A resolution to an R-value of 0.18. In the hypoxanthine binding site, a cis
      peptide bond between Asn243 and Lys244 is observed. Side-chains of GIu201 and
      Asn243, as well as one integral water molecule located in the base binding site,
      form hydrogen bonds with the hypoxanthine N-1 H, N-7 H and O-6. A second water
      molecule links the base positions N-3 and N-9 with an adjacent pocket, which
      presumably is the phosphate-binding site. This pocket is filled completely by a
      cluster of six water molecules. Hence all possible donor/acceptor-positions of
      hypoxanthine are saturated by hydrogen-bonding to protein side-chains or integral
      water molecules. Purine nucleoside phosphorylase isolated form human tissues is a
      primary target for chemotherapeutic intervention, and the more stable calf enzyme
      has similar physico-chemical and kinetic properties, as well as response to
      inhibitors. Hence the high-resolution structure presented here may serve for
      design of inhibitors with potential pharmacological applications.

PMID- 9020984
TI  - MONSSTER: a method for folding globular proteins with a small number of distance
      restraints.
AB  - The MONSSTER (MOdeling of New Structures from Secondary and TEritary Restraints)
      method for folding of proteins using a small number of long-distance restraints
      (which can be up to seven times less than the total number of residues) and some
      knowledge of the secondary structure of regular fragments is described. The
      method employs a high-coordination lattice representation of the protein chain
      that incorporates a variety of potentials designed to produce protein-like
      behaviour. These include statistical preferences for secondary structure, side
      chain burial interactions, and a hydrogen-bond potential. Using this algorithm,
      several globular proteins (1ctf, 2gbl, 2trx, 3fxn, 1mba, 1pcy and 6pti) have been
      folded to moderate-resolution, native-like compact states. For example, the 68
      residue 1ctf molecule having ten loosely defined, long-range restraints was
      reproducibly obtained with a C alpha-backbone root-mean-square deviation (RMSD)
      from native of about 4. A. Flavodoxin with 35 restraints has been folded to
      structures whose average RMSD is 4.28 A. Furthermore, using just 20 restraints,
      myoglobin, which is a 146 residue helical protein, has been folded to structures
      whose average RMSD from native is 5.65 A. Plastocyanin with 25 long-range
      restraints adopts conformations whose average RMSD is 5.44 A. Possible
      applications of the proposed approach to the refinement of structures from NMR
      data, homology model-building and the determination of tertiary structure when
      the secondary structure and a small number of restraints are predicted are
      briefly discussed.

PMID- 9020985
TI  - When a module is also a domain: the role of the N terminus in the stability and
      the dynamics of immunoglobulin domains from titin.
AB  - In the course of a structural study of titin, a giant modular protein from
      muscle, we have reported that N-terminal extension of immunoglobulin-like (Ig
      like) domains from titin stabilizes this fold. In order to investigate the
      structural basis of such an effect, we have solved the structure of NEXTM5, which
      has six amino acids added to the sequence of M5, a domain for which full
      structure determination has been previously achieved. In the present work, the
      structures and the dynamics of M5 and NEXTM5 are compared in the light of data
      collected for these and other titin domains. In NEXTM5, three out of the six
      added residues are structured and pack against the nearby BC and FG loops. As a
      consequence, three new backbone hydrogen bonds are formed with the B strand,
      extending the A strand by two residues and decreasing the exposed surface area of
      the loops. Additional contacts which involve the side-chains give rise to a
      remarkable pH dependence of the stability. Interestingly, no correlation is
      observed on the NMR time-scale between the overall dynamics of the extended
      domain and its increased stability. The most noticeable differences between the
      two constructs are localised around the N terminus, which becomes more rigid upon
      extension. Since a similar pattern of contacts is observed for other domains of
      the immunoglobulin I-set, our results are of general relevance for this protein
      family. Our work might also inspire a more rational approach to the investigation
      of domain boundaries and their influence on module stability.

PMID- 9020986
TI  - Prion protein gene variation among primates.

PMID- 9020987
TI  - Mental health care systems and their characteristics: a proposal.
AB  - The last 30 years have seen a significant growth in health service evaluation
      literature in the field of mental health. Much of the best of this research has
      taken the form of random control trials of an experimental service against
      "standard' or generic care. Interpretation of these results has ben hampered by
      incomplete and inconsistent approaches to describing the experimental services,
      and often inadequate or completely non-existent characterization of the control
      service. In addition, the health care system in which the treatment programme is
      embedded is known to have important consequences for outcome. A proposal is
      advanced for a structured service description as a routine component for health
      services research reporting. Two worked examples are given, and a number of areas
      of ambiguity are highlighted.

PMID- 9020988
TI  - Determinants of self-rating and expert rating concordance in psychiatric out
      patients, using the affective subscales of the CPRS.
AB  - To investigate in more detail concordance between the recently developed
      Comprehensive Psychopathological Rating Scale (CPRS) and the recently developed
      Self-Rating Scale for Affective Syndromes (CPRS-S-A), a total of 101 psychiatric
      out-patients were assessed using these procedures and a diagnostic interview
      according to DSM-III-R. Depressive and anxiety syndromes were the most common
      diagnoses on Axis I. Approximately one-third of the patients had a diagnosis of
      clinical personality disorder on Axis II. The majority of the patients were
      assessed as predominantly manifesting either Cluster B or Cluster C traits. In
      general, the correlation between self- and expert-ratings was strong (0.83 for
      the Montgomery-Asberg Rating Scale (MADRS) depression subscale and 0.76 for the
      Brief Scale for Anxiety (BSA) anxiety subscale), but it tended to be weaker in
      the group of patients with clinical personality disorders. The correlation
      between the two ratings was also weaker in the group with predominantly Cluster B
      character traits than in the group with predominantly Cluster C traits or the
      group with no predominant traits, and weaker in the depressive group than in the
      anxiety group. However, personality disorder diagnoses were over-represented in
      the depressive group. The weaker correlations in the groups mentioned above may
      have been attributable to psychological factors and qualitative differences in
      cognitive and communicative style. The CPRS-S-A is considered to be a useful and
      reliable instrument for quantitative rating of symptoms in out-patients. Our
      results highlight the potential value of using appropriate self-assessment forms
      as complementary tools in clinical practice and research.

PMID- 9020989
TI  - A 22- to 25-year follow-up study of former child psychiatric patients: a register
      based investigation of the course of psychiatric disorder and mortality in 546
      Danish child psychiatric patients.
AB  - A total of 546 children and adolescents, aged 5 to 15 years, who were admitted as
      in-patients to psychiatric hospitals throughout Denmark between 1970 and 1973,
      were followed up with regard to later readmissions and mortality. Approximately
      one-third of the sample had at least one readmission after the age of 18 years;
      there was no significant difference between male and female subjects. Probands
      with three selected diagnoses, namely childhood neurosis, conduct disorder and
      maladjustment reactions, did have a significantly greater general risk of
      readmission to psychiatric hospital in adulthood than the background population.
      In total, 24 probands (22 male, and 2 female subjects) died during the study
      period. Eight subjects had committed suicide. The standard mortality rate was
      significantly increased.

PMID- 9020990
TI  - A double-blind randomized placebo-controlled study of the efficacy and safety of
      pirlindole, a reversible monoamine oxidase A inhibitor, in the treatment of
      depression.
AB  - The efficacy and safety of pirlindole (300 mg/day), a new reversible inhibitor of
      monoamine oxidase A, have been evaluated in a multicentre placebo-controlled
      double-blind randomized trial in 103 in-patients suffering from unipolar major
      depression (DSM-III-R 296.2, 296.3) over a 42-day period after a run-in placebo
      period of 6 days. Pirlindole produced a significantly greater decrease than
      placebo in the Hamilton depression score (from day 28), the Hamilton anxiety
      score (from day 28) and the Montgomery-Asberg depression score (on day 42). On
      day 42, the Hamilton depression score was < or = 7, > or = 8 and < or = 15, or >
      or = 16 in 21%, 45% and 34%, respectively, in the placebo group compared to 72%,
      24% and 3.4%, respectively, in the pirlindole group (P < 0.001). The differences
      between the two groups in terms of tolerance and safety were not statistically
      significant.

PMID- 9020991
TI  - Screening of somatization disorder: validation of the Spanish version of the
      Othmer and DeSouza test.
AB  - The objective of this study was to validate the Spanish version of the Othmer and
      DeSouza Screening Test for Somatization Disorder. We have designed a validity
      study using the Standardized Polyvalent Psychiatric Interview, an instrument
      specifically designed to diagnose psychiatric morbidity in medical settings as
      the 'golden rule'. The control group displayed 'functional' and 'presenting'
      somatization. The Othmer and DeSouza Screening Test, with a threshold of three
      symptoms, shows 88% sensitivity, 78% specificity and a misclassification rate of
      17%. It is concluded that Othmer and DeSouza's screening test, with a threshold
      of three symptoms, is a useful tool for the diagnosis of somatization disorder in
      medical and primary care settings in Spain. Discrepancies with US findings are
      discussed on a cross-cultural basis.

PMID- 9020992
TI  - Biological predictors of suicidality in schizophrenia.
AB  - The objective of this study was to determine whether polysomnographic rapid eye
      movement (REM) sleep abnormalities and cortisol response to the dexamethasone
      suppression test (DST) differentiate between schizophrenic patients with and
      without a history of suicidal behaviour. We assessed a sample of 96 schizophrenic
      in-patients at the end of a 2-week medication-free period with the DST,
      polysomnography, and an extensive clinical assessment battery. Patients
      exhibiting suicidal behaviour were significantly more likely to have increased
      total REM time and increased total REM activity. We found no significant
      relationship between suicidal behaviour and DST non-suppression. This study
      confirms a previous finding suggesting an association between REM sleep
      abnormalities and suicidal behaviour in schizophrenia. It is postulated that this
      observed association may be related to serotonergic dysfunction in schizophrenia.

PMID- 9020993
TI  - Atypical depressive symptoms and clusters in unipolar and bipolar depression.
AB  - In order to examine differences in the atypical symptoms of depression between
      unipolar and bipolar patients, we studied 109 depressed patients (79 unipolar and
      30 bipolar subjects) diagnosed with DSM-IV criteria. Patients were assessed using
      the Atypical Depression Diagnostic Scale (ADDS), a semi-structured interview that
      rates mood reactivity and other atypical depressive symptoms. Although atypical
      depression was common in this sample (28% of cases with definite atypical
      depression), no differences were found between the unipolar and bipolar patients
      in either the atypical symptom profile or the prevalence of an atypical
      depression diagnosis. The interrelationships between the atypical symptoms were
      also examined using a hierarchical cluster analysis. A five-cluster solution
      maximized differences between groups, with results suggesting that atypical
      depression may be a heterogeneous diagnosis.

PMID- 9020994
TI  - Married patients with eating disorders in Japan.
AB  - A total of 40 married and 22 unmarried female patients with eating disorders were
      studied in order to investigate the relationship between eating disorders and
      marriage. Eating disorders developed in 14 patients before marriage (premarital
      onset) and in 26 patients at the time of or after marriage (postmarital onset).
      The postmarital-onset group was characterized by a significantly higher age at
      onset, but was similar in age and duration of illness to the group of 22
      unmarried patients. However, the various clinical features of the three groups
      did not differ. For premarital-onset patients showed exaggerated clinical
      features after marriage, but the other patients showed no change in clinical
      features after marriage. In the postmarital-onset group, eating disorders were
      triggered in 18 patients (69%) by marital problems, separation or divorce. In
      contrast, eating disorders were triggered by dieting in order to lose weight in 8
      patients (57%) in the premarital-onset group and 12 patients (55%) in the
      unmarried group. These results suggest that marital conflict plays an important
      role in the development and continuation of eating disorders in married women.

PMID- 9020995
TI  - The content and characteristics of auditory hallucinations in Saudi Arabia and
      the UK: a cross-cultural comparison.
AB  - This study investigated the content and characteristics of auditory
      hallucinations reported by 75 patients in Saudi Arabia (SA) and the UK. Each
      patient was asked to report on the content and characteristics of their
      hallucinations with regard to several dimensions, including loudness, frequency,
      clarity and perceived validity. In general, the characteristics of the voices did
      not vary between the SA and UK patients, but the content differed between
      cultures. Much of the content of the hallucinations of SA patients was religious
      and superstitious in nature, whereas instructional themes and running commentary
      were common in the UK patients. The results suggest that cultural differences
      need to be taken into account when applying psychological methods to this group
      of patients.

PMID- 9020996
TI  - Heritability of personality disorder traits: a twin study.
AB  - Genetic and non-genetic influences on the hierarchy of traits that delineate
      personality disorder as measured by the Dimensional Assessment of Personality
      Problems (DAPP-DQ) scale were examined using data from a sample of 483 volunteer
      twin pairs (236 monozygotic pairs and 247 dizygotic pairs). The DAPP-DQ assesses
      four higher-order factors, 18 basic dimensions and 69 facet traits of personality
      disorder. The correlation coefficients for monozygotic and dizygotic twin pairs
      ranged from 0.26 to 0.56 and from 0.03 to 0.41, respectively. Broad heritability
      estimates ranged from 0 to 58% (median value 45%). Additive genetic effects and
      unique environmental effects emerged as the primary influences on these scales,
      with unique environmental influences accounting for the largest proportion of the
      variance for most traits at all levels of the hierarchy.

PMID- 9020997
TI  - A pilot evaluation of the EMBU Scale in Japan and the USA.
AB  - Cultural differences in parental attitudes and child-rearing practices among
      European countries have been demonstrated in previous studies using a scale for
      assessment of memories of upbringing (the EMBU). In this pilot study we evaluated
      the EMBU in two previously unstudied populations: a culturally homogeneous sample
      from Japan (n = 105) and a culturally mixed sample from Southern California (n =
      73). The results suggest that, compared to European parents, Japanese parents are
      more emotionally distant from their children, while the Southern Californians as
      a group scored similarly to the Europeans. Further studies are needed in order to
      establish the EMBU as a transcultural tool for assessment of parental rearing
      behaviour.

PMID- 9020998
TI  - Preservation of hypothalamic-pituitary-adrenal axis fast-feedback responses in
      depression.
AB  - Depression is associated with overactivity of the hypothalamic-pituitary-adrenal
      (HPA) axis, which may be attributable to defective negative feedback. Fast
      feedback is the earliest phase of this, and has previously been suggested to be
      abnormal. A total of 30 physically healthy volunteers, 15 patients with DSM-III-R
      major depression and an age- and sex-matched control group received a
      standardized challenge of hydrocortisone (5 micrograms kg-1 min-1) or placebo
      over a period of 1 h. ACTH1-39 responses to hydrocortisone challenge did not
      differ significantly between healthy volunteers and patients with major
      depression. The fast-feedback response to hydrocortisone challenge is preserved
      in major depression when ACTH is measured directly.

PMID- 9020999
TI  - Mortality in anorexia nervosa in Denmark during the period 1970-1987.
AB  - In this nation-wide register linkage study of the mortality among psychiatric in
      patients with anorexia nervosa who were admitted between 1970 and 1986 (n = 853),
      50 deaths were recorded during a mean follow-up period of 7.8 years (6680 person
      years of observation). Among male subjects, five of 63 probands died, and the
      mean age at death was 24.5 years (range 14.2-48.1 years). Among female subjects,
      45 of 790 probands died, and the mean age at death was 36 years (range 18.1-64.7
      years). The standardized mortality ratio (SMR) was 9.1 in both sexes. A
      significantly increased SMR was demonstrated in males up to 5 years after index
      admission, and for females up to 15 years. There was no mortality among childhood
      onset female subjects, but among males one death was recorded in this age group.
      In male subjects the highest SMR was found among those with index admission in
      the second decade of life, and in females among those with index admission in the
      third decade of life. The SMR was maximal during the first year after index
      admission. Suicide was the dominant cause of death among subjects who died from
      unnatural causes (18 of 22 cases). Among those who died from natural causes (24
      subjects), 13 individuals died from anorexia nervosa and 11 individuals died from
      other illnesses.

PMID- 9021000
TI  - Acute and transient psychotic disorder: comorbidity with personality disorder.
AB  - A study sample of 51 patients with acute and transient psychotic disorder (ATPD)
      (ICD-10) is presented. The findings suggest that, in hospital settings, ATPD is a
      non-frequent condition with onset in early adult life and most often associated
      with female sex, good premorbid social functioning and no or minor/moderate
      psychosocial stressors. The DSM-IV criteria distribute the patients into three
      diagnostic categories: schizophreniform disorder (41%), brief psychotic disorder
      (33%) and psychotic disorder not otherwise classified (25%). A high prevalence
      (63%) of personality disorders (PD) is revealed after recovery from the psychotic
      episode. The ATPD is not related to any specific PD, and in a substantial
      minority (37%) of cases no PD is found. The unspecified category is by far the
      most frequent PD in patients with ATPD. The sample will be followed up and
      reassessed.

PMID- 9021001
TI  - Elevated tryptophan levels in post-withdrawal alcoholics.
AB  - Changes in serotonin function and disturbances in tryptophan availability have
      been implicated in many psychiatric disorders, including alcoholism. In the
      present study we took serum free tryptophan samples from 31 healthy volunteer
      controls and from 42 DSM-III-R alcohol-dependent subjects who had abstained from
      alcohol for at least 2.5 weeks (range 2.5-104 weeks). We also measured the basal
      serum cortisol level at 09.00 hours for the same subjects and controls. There was
      a significant increase in the serum tryptophan level of the alcoholic subjects,
      by 43.7 mumol l-1 (range 29-63 mumol l-1), regardless of age of onset of
      alcoholism, family history of alcoholism or sociopathic traits, compared to the
      controls (33.0 mumol l-1, range 19-60 mumol l-1). There was also an increase in
      the basal serum cortisol level in the alcoholic subjects compared to the
      controls, but this was not related to the increase in tryptophan levels. These
      findings indicate a disturbance in serotonin precursor availability in post
      withdrawal alcoholics, and contribute to the evidence for involvement of the
      serotonin system in alcoholism.

PMID- 9021002
TI  - Specific P300 features in patients with cycloid psychosis.
AB  - In previous studies, low amplitudes and asymmetrical topography with right-sided
      peaks of the P300-evoked response have been repeatedly described in schizophrenic
      patients. A total of 18 patients with cycloid psychosis fulfilling the criteria
      of Perris and Brockington and 18 controls were investigated with a standard
      auditory odd-ball paradigm and multichannel-evoked potential recordings. Patients
      had normal P300 topographies and latencies but significantly higher amplitudes
      than controls. Higher than normal P300 amplitudes have not been described in any
      other psychiatric disorder until now, and indicate an enhanced level of arousal.
      Future studies are expected to shed light on the question of whether high P300
      amplitudes are transitory sequelae of the acute psychotic episode or a trait of
      cycloid psychosis.

PMID- 9021003
TI  - Anhedonia, depression and the deficit syndrome of schizophrenia.
AB  - A total of 29 deficit schizophrenics were compared with 121 non-deficit
      schizophrenics using the Physical Anhedonia Scale (PAS) and the abridged form of
      the Beck Depression Inventory (BDI). The results show that the deficit
      schizophrenics had a higher score on the PAS and lower score on the BDI than the
      non-deficit schizophrenics.

PMID- 9021004
TI  - Oestradiol treatment helped a depressed postmenopausal woman to stop her
      psychotropic medication: a case report.
AB  - We report the case of a postmenopausal woman who had severe depression with
      psychotic features. She was treated over a period of 10 years with heavy
      psychotropic medication. Hormone replacement therapy alone replaced the
      medication and had an even better effect on her affective symptoms. Increasing
      serum oestradiol levels were correlated with improvement in mood.

PMID- 9021005
TI  - Restless legs syndrome and paroxetine.
AB  - Restless legs syndrome is a frequent dyssomnia with well-known clinical features
      but uncertain origin and treatment. This paper describes a case of restless legs
      syndrome worsened by paroxetine. A possible pathogenic hypothesis related to the
      attributed neurochemical properties of the drug is proposed.

PMID- 9021006
TI  - Are blastogenetic anomalies sporadic?
AB  - Opitz [Birth Defects, 1993, 1:3-37] postulated that sporadic defects of
      blastogenesis generally are highly lethal and have a low recurrence risk. We have
      observed that mothers of infants with blastogenetic defects have more previous
      abortions than mothers of children with nonblastogenetic defects or than mothers
      of control infants. Thus the high lethality of blastogenetic abnormalities may be
      responsible for the spontaneous abortions, and there may be a potential for an
      increased recurrence risk in some cases. Our results also show that the increased
      rate of spontaneous abortions is not similar for all blastogenetic defects, since
      it is not elevated in mothers of infants with neural tube defects (NTD). Further,
      our analysis does not confirm the relationship between spontaneous abortions in
      the preceding pregnancy and the occurrence of NTD previously reported by other
      authors.

PMID- 9021007
TI  - Brain anomalies, retardation of mentality and growth, ectodermal dysplasia,
      skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye
      hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia
      (BRESEK/BRESHECK): new X-linked syndrome?
AB  - Two half brothers (maternally related) had a similar syndrome of
      microhydrocephaly in both brothers and dilatation of the spinal canal with fusion
      of thalami in one brother. Primordial growth delay was noted in both brothers,
      with severe mental retardation in the surviving brother. Both had ectodermal
      dysplasia with scaling, hyperkeratosis, and generalized alopecia, but normal
      sweat and sebaceous glands. Skeletal anomalies included hemivertebrae with
      abnormal segmentation in one and scoliosis with polydactyly in the other. Ears
      were apparently low set, large, and protruding, with mixed hearing loss in the
      brother who survived. Eye anomalies included maldevelopment of one eye in Patient
      1 and small optic nerves more noticeable on one side in Patient 2. Both had
      cryptorchidism and dysplastic/hypoplastic kidneys of varying severity that
      resulted in the early postnatal death of one sib. Manifestations present in only
      one or the other sib included submucous cleft palate, aganglionosis of the rectum
      and colon, agenesis of one testicle, and single umbilical artery. This syndrome
      has not been described previously and may be due to an X-linked mutation. The
      acronym BRESEK reflects the common findings, whereas BRESHECK denotes all
      manifestations of both patients: brain, retardation, ectodermal dysplasia,
      skeletal deformities, Hirschsprung disease, ear/eye anomalies, cleft
      palate/cryptorchidism, and kidney dysplasia/hypoplasia. In addition to an X
      linked mutation, a contiguous gene deletion or maternal mosaicism of an autosomal
      dominant gene must be considered.

PMID- 9021008
TI  - Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with
      neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies.
AB  - We report on two sibs with syndromal congenital iron storage disease. Prenatal
      symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies
      included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical
      course was marked by intractable diarrhoea, with normal histological and
      enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30
      days, and progressive liver failure, leading to death after a few months. The
      only metabolic anomaly was progressive hypermethioninemia. Pathologic examination
      of both children showed a similar pattern of multivisceral iron deposit
      compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis
      or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and
      hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The
      unusual course for neonatal hemochromatosis in both sibs combined with concordant
      extrahepatic anomalies suggest that they could have a specific iron storage
      syndrome with possible autosomal recessive inheritance, probably similar to the
      sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].

PMID- 9021009
TI  - Multiple epiphyseal dysplasia, ribbing type: a novel point mutation in the COMP
      gene in a South African family.
AB  - Multiple epiphyseal dysplasia is broadly categorised into the more severe
      Fairbank and the milder Ribbing types. In this paper we document mild MED in a
      South African kindred, and demonstrate that heterozygosity for a mutation in the
      cartilage oligomeric matrix protein (COMP) gene causes the condition. The
      mutation, C1594G, implies a N523K substitution, altering a residue at the
      carboxyl-terminal end of the calmodulin-like region of COMP. The identification
      of this mutation demonstrates that the spectrum of manifestations from mild MED
      through pseudoachondroplasia can all be produced by structural mutations in COMP.

PMID- 9021010
TI  - Autosomal recessive lateralization and midline defects: blastogenesis recessive
      1.
AB  - In this report, we present 2 sibships in which midline and lateralization
      anomalies are demonstrated. Because midline and lateralization processes are
      early embryological events, we suggest calling this sequence Blastogenesis
      Recessive 1 (BGR1). Since connexin 43 gene mutations were demonstrated in some
      polyasplenia patients and according to connexin 43 temporospatial tissue
      expression, we hypothesize that this gene could bear mutations responsible for
      the anomalies reported in these two sibships.

PMID- 9021011
TI  - Blastogenesis dominant 1: a sequence with midline anomalies and heterotaxy.
AB  - Lateralization defect is a heterogeneous condition with different modes of
      transmission (autosomal recessive, dominant or X-linked). Here, we report on 3
      additional families that contribute to the description of phenotypic anomalies of
      the autosomal dominant type. Phenotypic anomalies include: lateralization
      defects, cardiac malformations, diaphragmatic hernia, urologic and neurologic
      anomalies. We suggest calling this sequence BGD1 for blastogenesis dominant 1
      because the deleterious effect probably occurs during blastogenesis and involves
      not only lateralization but other defects as well.

PMID- 9021012
TI  - Paracentric inversion involving the long arm of chromosome 9 resulting in
      deletion of abl gene.
AB  - We report on a new chromosomal finding in a newborn male with hypertelorism,
      apparently low-set malformed ears with patent canal, micrognathia with narrow
      high-arched palate, bilateral webbing of neck with low posterior hairline, widely
      spaced nipples, and complex heart anomalies. Initially, what appeared to be a
      simple paracentric inversion of the long arm of chromosome 9, that is, 46,XY,
      inv(9)(q31q34) by routine GTG-banding technique was later determined to be a
      paracentric inversion with deletion of the band 9q34.1 by FISH technique using an
      abl unique sequence DNA probe. Thus the cytogenetic diagnosis was modified to
      46,XY,der(9) inv(9)(q31q34.1)del(q34.1). Nevertheless, the presence of telomeric
      repeat sequences in the inverted chromosome 9 suggests that either healing has
      occurred by adding [TTAGGG]n sequences to the non-telomeric end (q31) by the
      enzyme telomerase or telomeric sequences were not affected during this inversion
      process. This abnormality is a rare occurrence and has never been reported before
      either because of a high rate of lethality or it has been undetected by routine
      cytogenetic techniques. The other abnormal cases with apparent paracentric
      inversions could also have a complex nature with congenital anomalies associated
      with loss of "few" DNA sequences as exemplified here.

PMID- 9021013
TI  - Dominance and homozygosity.
AB  - Because of the high consanguinity rates in many communities in Israel we had the
      opportunity to study homozygosity for some dominant disorders. This experience
      and a review confirmed that in most cases homozygotes of dominant disorders are
      more severely affected than heterozygotes. In some cases molecular analysis
      allowed an understanding of the mechanisms involved. While heterozygosity for
      point mutations or deletions of PAX3 lead to similar manifestations (Waardenburg
      syndrome), in homozygotes the phenotype is much more severe, probably in direct
      relation to the loss of function. Charcot-Marie-Tooth 1A is caused by a
      duplication of PMP22 and further over-expression lead to a more severe disorder.
      In diseases in which the mutation leads to an abnormal structural protein, the
      homozygote may be as severely affected as the heterozygote (epidermolysis bullosa
      simplex) or more severely (achondroplasia, Marfan syndrome). The polyglutamine
      tract is translated in disorders caused by CAG triplet expansions. In homozygotes
      for Machado-Joseph disease the onset is earlier and the symptoms are more severe
      than in heterozygotes, while in Huntington disease homozygotes are affected like
      heterozygotes.

PMID- 9021014
TI  - A complex chromosome rearrangement with at least five breakpoints studied by
      fluorescence in situ hybridization.
AB  - A newborn infant with multiple congenital anomalies was diagnosed with an
      unbalanced translocation of chromosomes 1 and 5. Studies of parental chromosomes
      revealed a complex rearrangement in the patient's mother involving the exchange
      of terminal long arms between chromosomes 1 and 5 and the insertion of an
      interstitial segment from the same chromosome 5q into chromosome 2q by high
      resolution G-banding. Further study of the mother's chromosomes by fluorescent in
      situ hybridization (FISH) detected an additional insertion between the rearranged
      chromosomes 2 and 5, which was not revealed by G-banding. This led to the
      identification of a complex translocation-insertion between 3 chromosomes with at
      least 5 breaks [t(1;5;2)(1pter--> 1q42.3::5q23.2-->5qter;5pter-->5q21.2:: 2q33-->
      2q35::1q42.3-->1qter;2pter-->2q33::5q21 .2--> 5q23.2::2q35-->2qter)] and
      illustrates the value of FISH as an adjunct to standard cytogenetics,
      particularly in cases of complex rearrangements.

PMID- 9021015
TI  - Ritscher-Schinzel (3C) syndrome: documentation of the phenotype.
AB  - Ritscher-Schinzel syndrome or 3C (craniocerebello-cardiac) syndrome is
      characterized by cardiac defects, cerebellar vermis hypoplasia, and cranial
      defects. Nineteen cases were reported previously; however, the full spectrum of
      this disorder has not been determined. We have evaluated two unrelated males with
      this condition. Both had defects of the endocardial cushion and vermis hypoplasia
      with hypotonia. In addition, both had hypospadias, a previously undescribed
      finding of this disorders. Review of the previously reported cases and those
      described herein demonstrate: 1) Although varying degrees of vermis hypoplasia
      are accompanied by hypotonia, delayed gross motor function improves with
      advancing age leaving speech delay as the major neurodevelopmental handicap. 2)
      Two different types of cardiac anomalies occur: defects of the endocardial
      cushion ranging from anomalies of the mitral or tricuspid valves to complete AV
      canal, and/or conotruncal defects. 3) Postnatal growth deficiency was seen in
      most patients in whom longitudinal information was available. In our review of
      patients with vermis hypoplasia we ascertained a patient diagnosed as having
      "Joubert syndrome" who had most findings of the Ritscher-Schinzel syndrome and
      several other patients with "Dandy-Walker syndrome" who likely have had Ritscher
      Schinzel syndrome, suggesting that Ritscher-Schinzel syndrome is more common than
      has been appreciated. Careful search for the subtle facial changes characteristic
      of this disorder as well as coloboma, cleft palate/bifid uvula, short neck,
      syndactyly, and hypoplasia of the nails is warranted when evaluating children
      with Dandy-Walker malformation with or without clinical signs of Joubert
      syndrome.

PMID- 9021016
TI  - Delineation of a duplication map of chromosome 3q: a new case confirms the
      exclusion of 3q25-q26.2 from the duplication 3q syndrome critical region.
AB  - We report on the clinical, cytogenetic, and molecular characterization of a
      propositus and his mother with a duplication of 3q25-q26, minor anomalies, and
      mental retardation. The duplication, detected by cytogenetic analysis, was
      confirmed and delineated by comparative genomic hybridization and fluorescence in
      situ hybridization using probes previously mapped to the region. Comparison of
      the mapping data obtained in these patients and those obtained in patients that
      present with a typical dup(3q) syndrome phenotype shows that the segment
      duplicated in these patients lies proximally to the reported dup(3q) syndrome
      critical region, thus explaining the absence in our patients of the
      characteristic phenotype of dup(3q) syndrome patients. Accumulation of mapping
      data in patients with segmental duplications of 3q will eventually allow us to
      build a duplication map of the region and a genotype-phenotype correlation.

PMID- 9021017
TI  - Comparison of phenotype between patients with Prader-Willi syndrome due to
      deletion 15q and uniparental disomy 15.
AB  - Prader-Willi syndrome (PWS) is a complex multiple anomaly syndrome that has been
      shown to result from deficient expression of paternal chromosome 15(q11-q13). In
      most cases, it is caused either by deletion of this region in the paternally
      inherited chromosome 15 or by maternal uniparental disomy (UPD) of chromosome 15.
      In order to determine whether there are phenotypic differences between patients
      whose PWS is caused by these two different mechanisms, 54 affected individuals
      (37 with deletion, 17 with UPD) were personally examined and studied using
      molecular techniques. The previously recognized increased maternal age in
      patients with UPD and increased frequency of hypopigmentation in those with
      deletion were confirmed. Although the frequency and severity of most other
      manifestations of PWS did not differ significantly between the two groups, those
      with UPD were less likely to have a "typical" facial appearance. In addition,
      this group was less likely to show some of the minor manifestations such as skin
      picking, skill with jigsaw puzzles, and high pain threshold. Females and those
      with UPD were also older, on average. Possible mechanisms by which these
      differences could occur and the implications of these differences for diagnosis
      are described.

PMID- 9021018
TI  - Diaphragmatic hernia-exomphalos-hypertelorism syndrome: a new case and further
      evidence of autosomal recessive inheritance.
AB  - We describe a male patient with wide anterior fontanel and metopic suture,
      hypertelorism, down slanting palpebral fissures, bilateral iris coloboma,
      omphalocele, and bilateral absence of the diaphragm with herniation of abdominal
      organs causing pulmonary hypoplasia and death. Autopsy also showed intestinal
      malrotation. All findings in this case are consistent with those described as a
      newly recognized syndrome by Donnai and Barrow [1993]. Since the parents are
      first cousins, this case provides further evidence for the previously postulated
      autosomal recessive inheritance pattern. Follow-up on the patients and families
      reported by Donnai and Barrow [1993] also supports autosomal recessive
      inheritance.

PMID- 9021019
TI  - Transmission electron microscopy of chromosomes by longitudinal section
      preparation: application to fragile X chromosome analysis.
AB  - We developed a method for the preparation of ultrathin longitudinal sections of
      chromosomes enabling TEM studies of whole chromosomes. By using a novel "repeat
      chill" method of exposing the glass slide and plastic block interface to liquid
      nitrogen, it was possible to separate consistently hardened epoxy resin-embedded
      chromosome spreads from glass slides for ultrathin longitudinal sectioning of
      entire spreads and of individual chromosomes. The method was applied to analyze
      the fragile X chromosome. The ultrastructure of centromeres, telomeres, fragile
      sites and other chromosomal areas can now be studied in detail.

PMID- 9021020
TI  - Mild "duplication 6q syndrome": a case with partial trisomy (6)(q23.3q25.3).
AB  - We report on a female infant with partial 6q trisomy (46,XX,dir
      dup(6)(q23.3q25.3)) and phenotypic characteristics of the "duplication 6q
      syndrome," including intrauterine growth retardation, dolichocephaly, depressed
      nasal bridge, almond-shaped palpebral fissures, short neck, flexion-contractures
      of the wrists, and mild generalized hypertonia. Although clearly belonging to the
      described "duplication 6q syndrome," her features were milder than those found in
      the literature. Comparison of the phenotype of this child with other published
      reports indicates that specific phenotypic components of the duplication 6q
      syndrome cannot be attributed to duplication of a specific band or bands on 6q.

PMID- 9021021
TI  - Microcephaly, muscular build, rhizomelia, and cataracts: description of a
      possible recessive syndrome and some comments on the use of electronic databases
      in syndromology.
AB  - We report on a 7-year-old boy born of consanguineous parents with severe
      microcephaly (-5 SD) but borderline intelligence, juvenile cataract, muscular
      build, rhizomelic shortness of limbs predominantly of femora, advanced bone age,
      and micropenis. This combination of signs appears unique and may represent an
      undescribed, possibly autosomal recessive MCA syndrome. The use of LDDB and
      POSSUM in the workup of such "new syndromes" is reviewed. Three search strategies
      are discussed: single rare sign browsing, best combinatory fit using an array of
      key words, and combined rare signs scan. Pitfalls in the use of such databases
      and the some problems raised by inconsistent/ incomplete encoding in those two
      popular, highly useful syndromology retrieval systems are discussed.

PMID- 9021022
TI  - The neuroimaging findings in Sotos syndrome.
AB  - We reviewed the neuroimaging studies of 40 patients with classic Sotos syndrome.
      The studies consisted of CT scans only in 4 patients and one or more MRI scans in
      36 patients. The diagnosis of Sotos syndrome was made using well-established
      clinical criteria. The neuroimaging studies of each patient were evaluated
      subjectively by visual inspection and the chief findings were tabulated and
      grouped into five categories: 1) ventricular abnormalities, 2) extracerebral
      fluid spaces, 3) midline abnormalities, 4) migrational abnormalities, and 5)
      others. The most common abnormality of the cerebral ventricles was prominence of
      the trigone (90%), followed by prominence of the occipital horns (75%) and
      ventriculomegaly (63%). The supratentorial extracerebral fluid spaces were
      increased for age in 70% of the patients and the fluid spaces in the posterior
      fossa were increased in 70% also. A variety of midline abnormalities were noted
      but anomalies of the corpus callosum were almost universal. Gray matter
      heterotopias occurred in only 3 (8%) of 36 patients. Periventricular
      leukomalacia, presumably the result of prenatal or perinatal difficulties and
      unrelated to the basic condition, was the most common of the miscellaneous other
      abnormalities noted. The neuroimaging findings of Sotos syndrome are distinct
      enough to allow differentiation of this syndrome from other mental retardation
      syndromes with macrocephaly.

PMID- 9021023
TI  - Pattern of malformations in the axial skeleton in human trisomy 21 fetuses.
AB  - In the present study, we analyzed the development of the axial skeleton in human
      trisomy 21 fetuses and defined the fields in the axial skeleton affected in this
      form of aneuploidy. We investigated 31 human fetuses with trisomy 21, gestational
      ages 12-24 weeks, on the basis of radiographs of midsagittal tissue blocks of the
      axial skeleton, comprising the cranial base and the spine. Malformation or
      agenesis of the nasal bone was present in 19 of 31 fetuses. Nineteen cases had
      vertebral malformations. Fourteen fetuses had malformations in the cervical
      region, four in the thoracic and eight in the lumbosacral region. In 1 of 31
      fetuses, malformation was seen in the basilar part of the occipital bone. The
      basisphenoid component appeared scallop-shaped in 30 cases. The pattern of axial
      skeletal malformations in trisomy 21 fetuses recorded here has not been described
      previously. Comparison is made with our recent study of trisomy 18, where the
      pattern of axial skeletal malformations was quite different. It is recommended
      that axial skeletal radiography should be part of the autopsy of fetuses where
      chromosome abnormalities are known or suspected.

PMID- 9021024
TI  - Genetic disorders among Palestinian Arabs: 1. Effects of consanguinity.
AB  - Among Palestinian Arabs the rate of consanguinity is very high and some 44.3% of
      the marriages are between relatives (22.6% of them between first cousins). In
      almost 2,000 files from Palestinian Arab families who attended the genetics
      clinic in the Hadassah Medical Center; we were able to study the effects of
      consanguinity on different disorders. The consanguinity rate in families with
      dominant or X-linked disorders and chromosome aberrations was similar to the one
      observed in the general population. We did not find any significant differences
      in the rate of consanguineous marriages between the parents and grandparents of
      children affected with trisomy 21 and the general population. Thus, we were not
      able to confirm the suggestion that there is an increase risk for trisomies in
      children/grandchildren of consanguineous parents. Among the parents of patients
      with rare autosomal recessive disorders the consanguinity rate was much higher
      than the one of the general population (92.5%). Among the autosomal recessive
      disorders, which were relatively frequent in the population, there were fewer
      marriages between relatives; but in most cases the difference from rare disorders
      is relatively small. The importance of genetic factors in various congenital
      malformations, such as neural tube defects and cleft lip/palate or in various
      forms of infertility, was confirmed by the observation of a significantly higher
      consanguinity rate in the parents of these patients than is observed in the
      general population.

PMID- 9021026
TI  - Tetrasomy 5p mosaicism due to an extra i(5p) in a severely affected girl.
AB  - We present a case of mosaic 5p tetrasomy. The mosaicism 46,XX/47,XX,+i(5p) was
      found at different ratios in blood lymphocytes, skin fibroblasts, and
      chondrocytes. The origin of the extra isochromosome was confirmed by FISH. The
      clinical picture corresponds to that described in trisomy 5p patients, although
      it was more severe than the two previously reported cases of mosaic 5p tetrasomy.
      No correlation between clinical severity and proportion of tetrasomic cells in
      blood or fibroblasts was found in these cases.

PMID- 9021025
TI  - Proximal partial 5p trisomy resulting from a maternal (19;5) insertion.
AB  - We present a case with a partial duplication 5p11-->5p13.3 resulting from a
      maternal ins (19,5)(p11;p11-p13.3). The diagnosis was confirmed by FISH and
      complement component determinations. The clinical picture was similar to those
      described in patients with complete duplication of the short arm and in some
      patients with partial 5p duplications, affecting at least band 5p13. A special
      significance of band 5p13 in the clinical severity of 5p duplications is
      discussed.

PMID- 9021027
TI  - Problem of offering unsolicited clinical genetic advice and diagnoses to
      nonmedical friends and strangers.

PMID- 9021028
TI  - Photographic documentation of syndrome diagnosis.

PMID- 9021029
TI  - Association of a polymorphic variant of the Werner helicase gene with myocardial
      infarction in a Japanese population.
AB  - The Werner syndrome (WS) is a rare autosomal recessive progeroid syndrome
      characterized by the premature onset of multiple age-related disorders, including
      atherosclerosis, cancer, non-insulin-dependent diabetes mellitus (NIDDM), ocular
      cataracts and osteoporosis [Epstein et al., 1966]. The major cause of death (at a
      median age of 47) is myocardial infarction (MI) [Epstein et al., 1966]. The WS
      mutation involves a member (WRN) of the RecQ family of helicases and may perturb
      DNA replication, repair, recombination, transcription, or chromosomal segregation
      [Yu et al., 1996]. We now report data on 149 MI cases and age-matched controls
      suggesting that a polymorphic WRN variant is associated with increased risk for
      MI. Based on our data, homozygosity for a cysteine at amino acid 1367 (the most
      prevalent genotype) predicts a 2.78 times greater risk of MI (95% confidence
      intervals: 1.23 to 6.86). The variant was not significantly associated with
      NIDDM. The two alleles (cysteine vs. arginine) could influence helicase activity,
      turnover, macromolecular interactions or, alternatively, could be markers for
      haplotypes influencing WRN regulation or reflecting gene action at linked loci.
      However, given the caveats implicit in genetic association studies, it is
      imperative that the present results be replicated in independent populations.

PMID- 9021030
TI  - Patterns of meniscal injury in the anterior cruciate-deficient knee: a review of
      the literature.
AB  - The importance of addressing meniscal pathology associated with anterior cruciate
      ligament (ACL) insufficiency stems from the increased incidence of meniscal tears
      with chronic instability. The combined effect of instability and meniscal lesions
      can lead to the development of knee arthrosis. A predominance of lateral meniscal
      tears has been demonstrated with acute ACL rupture, whereas the incidence of
      medial meniscal tears increases significantly with chronic ACL insufficiency. The
      percentage of repairable meniscal tears is higher on the medial than the lateral
      side and decreases overall with the chronicity of ACL insufficiency. The
      likelihood of a successful meniscal repair is enhanced significantly when
      combined with ACL reconstruction. This review suggests that maximal meniscal
      preservation is best achieved with ACL reconstruction. This review suggests that
      maximal meniscal preservation is best achieved with ACL reconstruction shortly
      after injury and simultaneous repair of coexisting peripheral meniscus tears.

PMID- 9021031
TI  - Assessing the need for extensive supervised rehabilitation following arthroscopic
      ACL reconstruction.
AB  - To determine the necessity of extensive supervised therapy, we reviewed the
      records of 39 consecutive patients who underwent arthroscopic anterior cruciate
      ligament reconstruction using mid-1/3 bone-patellar tendon-bone autograft,
      followed by a minimal therapy program. This study group was subdivided into a
      noncompliant group averaging 1.7 visits over 6 months (range, 0 to 5), (subgroup
      I), and a minimally compliant group averaging 12 visits over 6 months (range, 5
      to 24), (subgroup II). Thirty patients who underwent similar surgeries and
      postoperative protocols, but participated in an extensive supervised outpatient
      therapy program, served as controls. The control group was fully compliant and
      averaged 60 visits over 6 months. After 6 months, the minimally compliant study
      subgroup was equivalent to the fully compliant control group in Lysholm score,
      patient satisfaction, and return to preoperative activity level. Both of these
      groups fared better in all of these indices than did the noncompliant subgroup.
      These results suggest that extensive supervised rehabilitation does not afford a
      measurable advantage over a minimally supervised program of two visits monthly.
      Complete noncompliance, however, was associated with suboptimal outcome.

PMID- 9021032
TI  - Unilateral insensate macrodactyly secondary to tuberous sclerosis in a child.
AB  - Primary localized gigantism of the hand is exceedingly rare and has been reported
      only twice in the literature. Both cases were associated with tuberous sclerosis
      in which the patients had normal sensation. In this case report, a very unusual
      combination of insensate and unilateral macrodactyly in a child with tuberous
      sclerosis is described using both physical and roentgenographic findings.

PMID- 9021033
TI  - Proximal dissection of a popliteal giant synovial cyst: a case report.
AB  - Giant synovial cysts in patients with rheumatoid arthritis are well-recognized
      soft-tissue masses adjacent to the knee. Cases involving the elbow, hip, and
      other synovial joints have been reported as well. Regardless of location, these
      expanding, space-occupying lesions usually present with nonspecific symptoms of
      swelling and pain. Less commonly, the original presentation may be related to the
      secondary effects of the cyst on nearby anatomic structures. We present a case of
      a giant synovial cyst originating posteriorly in the knee, which, rather than
      dissecting distally into the calf, dissected proximally into the posterior soft
      tissue of the thigh in a patient with long-standing rheumatoid arthritis.

PMID- 9021034
TI  - Synovial chondromatosis: a case study and brief review.
AB  - Synovial chondromatosis is a benign synovial neoplasm, most often monoarticular.
      A case involving a 25-year-old Hispanic woman with a 2-year history of joint
      stiffness, locking, and recurrent effusion is presented. The diagnostic
      evaluation included standard roentgenograms, magnetic resonance imaging,
      arthrocentesis, and arthrography. She underwent arthrotomy and synovectomy.
      Multiple small cartilaginous bodies were removed during the procedure. At 3-year
      follow-up, the patient has not reported any residual problems, except for mild
      joint stiffness. This paper will discuss the physical findings, diagnostic
      studies, and management of intra- or extra-articular synovial chondromatosis.

PMID- 9021035
TI  - Colles' fracture: efficacy of pins and plaster.
AB  - Colles' fracture of the distal radius is a common injury; however, controversy
      exists over the treatment of unstable fractures of this type. A retrospective
      analysis of patients with distal radius fractures treated with pins and plaster
      was performed to assess the effectiveness of the technique. The study group
      comprised 73 patients (10 men and 63 women) with an average age of 64.7 years
      (range, 51 to 82). Roentgenographic measurements of radial height, radial angle,
      and volar angle were compared at initial and final treatment. Medical records
      were reviewed for complications. A difference in radial height of 1.6 mm was
      observed from the first postoperative visit to the final assessment (P = .001);
      however, this was not believed to be clinically significant. The differences in
      the radial and volar angles were negligible and not statistically significant.
      The complication rate was 55%, with the most common complication being some
      degree of residual finger and wrist stiffness (39%). Pin tract infection occurred
      in only 1 patient. The use of pins and plaster is a feasible alternative in the
      management of low-energy distal radius fractures.

PMID- 9021036
TI  - Use of a 14-gauge needle as a wire guide.
AB  - A thin guide wire needs a long guide to keep the wire centered on the bone. A 14
      gauge needle makes an inexpensive guide.

PMID- 9021037
TI  - Declining sperm quality in European men.

PMID- 9021038
TI  - Declining sperm counts? More research is needed.

PMID- 9021039
TI  - Declining sperm counts in Italy during the past 20 years.

PMID- 9021040
TI  - Declining sperm counts in European men--fact or fiction?

PMID- 9021041
TI  - Is semen quality declining?

PMID- 9021042
TI  - Effect of continual light deprivation and alpha-2u-globulin replacement therapy
      on serum concentration of gonadotropins and testicular activity in rats.
AB  - Prolonged darkness caused a fall in testicular 17 beta-hydroxysteroid
      dehydrogenase (17 beta-HSD) activity and diminished spermatogenesis, serum levels
      of gonadotropins, testosterone and alpha 2u-globulin. Administration of alpha 2u
      globulin at a dose of 1.5 mg rat-1 per day for 7 days after 68 days of light
      deprivation, reversed the 17 beta-HSD activity and serum levels of gonadotropins,
      testosterone and alpha 2u-globulin, while spermatogenesis was restored to normal.
      The animals kept in prolonged darkness for 68 days and then received saline (7
      days in light-dark cycle, 14 L: 10 D), showed no significant changes of
      testicular activity, serum levels of gonadotropins, testosterone and alpha 2u
      globulin, when compared with dark-exposed animals (68 days) receiving rabbit
      serum (7 days in light-dark cycle, 14 L: 10 D). These results suggest that alpha
      2u-globulin plays an important role in testicular function in dark-exposed rats
      by inducing gonadotropins and testosterone secretion.

PMID- 9021043
TI  - Effect of fluctuations in temperature encountered during handling and shipment of
      human cryopreserved semen.
AB  - The effect of temperature fluctuations which cryopreserved spermatozoa may
      undergo during routine shipping and handling was evaluated in sperm frozen with
      two cryoprotectants. Sperm frozen in TEST-yolk buffer maintained motility better
      than those frozen in glycerol solution in all studies. Sperm motility was
      significantly compromised in samples stored more than one day in dry ice,
      regardless of the cryoprotectant, and more than two days in a liquid nitrogen
      shipping dewar if frozen in glycerol solution. Sperm motility was not compromised
      following exposure to room temperature for up to 3 min if TEST-yolk buffer was
      used as the cryoprotectant, but was compromised following 1 min exposure using
      glycerol cryoprotectant. This study describes the limits of non-ideal conditions
      that spermatozoa may undergo during shipping and handling, and demonstrates the
      effects of the cryoprotectant on those limits.

PMID- 9021044
TI  - In vitro effects of substance P and arginine-vasopressin on testosterone
      production in Leydig cells of short and long photoperiodic hamsters.
AB  - The aim of the present study was to determine the interaction between substance P
      (SP) and arginine-vasopressin (AVP) on basal and LH-stimulated testosterone
      production by Leydig cells isolated from hamsters kept under long or short days
      (LD-hamsters, SD-hamsters, respectively). SP inhibited the testosterone
      production of Leydig cells, its effect being more pronounced in the case of LH
      stimulated steroidogenesis in LD-hamsters. Similarly, the addition of AVP to the
      culture medium resulted in a diminution of basal, as well as LH-stimulated
      testosterone secretions. When Leydig cells were co-incubated with SP (10(-7) M)
      and AVP (10(-7) M), a strong inhibition of the testosterone production by 50-60%
      was established in LD-animals. However, even within the experimental
      circumstances in SD-hamsters, the modulation of testosterone production by SP and
      AVP was evident. The reported results suggest that there is an interference of
      two regulatory pathways, namely photoperiodic dependence and paracrine control of
      testicular steroidogenesis in hamsters.

PMID- 9021045
TI  - Affinity sites for beta-glucuronidase on the surface of human spermatozoa.
AB  - Glycosidases secreted by the epididymis become bound to the surface of
      spermatozoa during their transit through the epididymal duct. They are believed
      to play a role in mammalian fertilization. In the present report, we demonstrate
      that beta-glucuronidase binds to the surface of ejaculated human spermatozoa with
      high affinity and in a saturable manner. The binding is Ca(2+)-independent,
      inhibited by either mannose-6-phosphate, phosphomannan fragments from the yeast
      Hansenula holstii and alpha-mannosidase from the Dictyostelium discoideum,
      suggesting that phosphomannosyl receptors are involved in the recognition of the
      enzyme. The catalytic site of the enzyme is not involved in the binding. The
      localization of the beta-glucuronidase binding-sites is restricted to the surface
      of the sperm head. These results suggest that the spermatozoa could be the target
      for glycosidases present in the seminal plasma.

PMID- 9021046
TI  - Mitotic frequency in different early stages of testicular seminoma.
AB  - The proliferation behaviour of early seminoma was studied by analysis of the
      mitotic frequency in defined stages of tumour development: Carcinoma in-situ,
      intratubular seminoma, intratubular seminoma with interstitial seminoma cells and
      solid seminoma. It was shown that the mitotic frequency increased during the
      process of tumour development and that tumour cells in different tissue
      compartments show a different proliferation behaviour. The first stage example
      (CIS) showed a mitotic frequency of 0.65% while the second stage example
      (intratubular seminoma) showed a mitotic frequency of 0.84%. The separated
      analysis of the third stage example (intratubular seminoma with interstitial
      seminoma cells) showed a mitotic frequency of 1.45% for the intratubular
      compartment and 0.72% for the interstitial compartment. The fourth stage example
      (solid seminoma) showed a mitotic frequency of 3.59%. The finding that mitotic
      frequencies differ in the examined stage examples are interpreted as an
      adaptation process of the tumour cells to a changed tissue micro-environment.
      Considering that little experimental data exists on the biological behaviour of
      early seminoma cells this study adds information to the present knowledge of
      their proliferation kinetics.

PMID- 9021047
TI  - Flat plastic embedding and precise longitudinal sectioning of isolated testicular
      seminiferous tubules.
AB  - A method is presented for the flat plastic embedding and precise longitudinal
      semithin sectioning of dissected individual seminiferous tubules. Following
      standard aldehyde- and OsO4-fixation, individual resin-immersed tubules are
      polymerized in an exactly flat position between the plan surfaces of a glass
      slide and an inverted pre-polymerized resin block. Each embedded tubule thus lies
      directly at the even surface of the resulting block and can subsequently be
      sectioned along its longitudinal course. The morphology of continuous, up to
      approximately 20 mm-long tubule segments may thus be immediately surveyed by high
      resolution light-microscopy and, if required, be studied at the ultrastructural
      level as well.

PMID- 9021048
TI  - Acrosin activity in pelleted frozen sperm does not correlate with in vitro
      fertilization of oocytes.
AB  - Spermatozoa pelleted after swim-up were frozen and then analysed in batches for
      acrosin activity, using a spectrophotometric method, and expressed as microIU
      micrograms DNA-1. A total of 259 sperm samples were analysed and the acrosin
      activity compared with fertilization in vitro. Of these, 224 samples fertilized
      at least one oocyte and 35 samples failed to fertilize any oocyte. Analysis by
      Student's t-test indicated that there was a statistically significant difference
      (P = 0.02) in acrosin activity between the two groups. However, when samples that
      failed to fertilize were matched for concentration, motility and normal
      morphology with samples that fertilized, this significance was lost (P = 0.77).
      It is concluded that total acrosin in pelleted sperm frozen after regular swim
      up, does not correlate with fertilizing ability of spermatozoa used for
      insemination.

PMID- 9021049
TI  - Assessment of pain in herpes zoster: lessons learned from antiviral trials.
AB  - Pain typically accompanies acute herpes zoster and, in a proportion of patients,
      it persists well beyond rash healing. Pain must therefore be analyzed in trials
      of antiviral agents in herpes zoster, but different methods have been used to
      analyze pain in recent published trials. These reports are reviewed and their
      methodological strengths and weaknesses examined. Based on this review,
      recommendations for the design and analysis of future trials of antiviral agents
      in herpes zoster are proposed. The principal recommendation is that antiviral
      efficacy should be evaluated both by distinguishing post-herpetic neuralgia from
      acute pain and by considering pain as a continuum. The primary endpoint should
      address both the prevalence and duration of post-herpetic neuralgia and should be
      examined in those patients who have post-herpetic neuralgia. Adopting the
      proposed recommendations in design and analysis of future trials should
      facilitate comparison across trials of the efficacy of antiviral agents in the
      treatment of herpes zoster.

PMID- 9021050
TI  - Antireplicative and anticytopathic activities of prostratin, a non-tumor
      promoting phorbol ester, against human immunodeficiency virus (HIV).
AB  - Prostratin, a non-tumor-promoting phorbol ester, inhibited human immunodeficiency
      virus (HIV)-induced cell killing and viral replication in a variety of acutely
      infected cell systems. The potency and degree of cytoprotection was dependent on
      both viral strain and host cell type. Prostratin activated viral expression in
      two latently-infected cell lines, but had little or no effect on chronically
      infected cell lines. Prostratin caused a dose-dependent, but reversible, decrease
      in CD4 expression in the CEM-SS and MT-2 cell lines. This down-regulation of CD4
      was inhibited in a dose-dependent manner by the protein kinase C (PKC)
      antagonist, staurosporine. In addition, the cytoprotective and cytostatic effects
      of prostratin in CEM-SS cells acutely infected with HIV-1RF were reversed by
      bryostatin-1, a PKC agonist. Prostratin had no effect on reverse transcriptase or
      HIV-1 protease, nor did it inhibit the binding of gp120 to CD4. We conclude that
      prostratin inhibits HIV cytopathicity and replication through mechanism(s)
      involving PKC enzyme(s).

PMID- 9021051
TI  - Pharmacokinetics and anti-HIV-1 efficacy of negatively charged human serum
      albumins in mice.
AB  - Negatively charged albumins (NCAs, with the prototypes succinylated human serum
      albumin (Suc-HSA) and aconitylated human serum albumin (Aco-HSA)), modified
      proteins with a potent anti-human immunodeficiency virus type 1 (anti-HIV-1)
      activity in vitro, were studied for their pharmacokinetic behaviour in mice and
      their in vivo anti-HIV-1 efficacy in an HIV-1 infection model in mice. In
      contrast to the saturation kinetics found in rats, intravenous injections of 10
      300 mg/kg for both NCAs showed a linear correlation between the area under the
      curve (AUC) and the dose. The elimination t1/2 was 25 and 30 min for Suc-HSA and
      Aco-HSA, respectively. Preinjections of an excess of formaldehyde-treated albumin
      (Form-HSA) resulted in plasma levels that were 3- and 4-fold higher for Aco-HSA
      and Suc-HSA, respectively. These data indicate that elimination is at least
      partly (scavenger) receptor-mediated. Organ distribution studies 10 min after
      injection showed an accumulation in liver (Suc-HSA 17.3 +/- 6.6% of the dose; Aco
      HSA 20.9 +/- 2.3%) and lungs (Suc-HSA 12.7 +/- 10.5%; Aco-HSA 16.0 +/- 13.6).
      Intraperitoneal injection of 300 mg/kg Suc-HSA resulted in a final
      bioavailability of about 0.45. Suc-HSA was also evaluated for its in vivo
      neutralizing capacity in a human-to-mouse chimeric model for HIV-1 infection.
      Intraperitoneal injections of 300 and 3 mg/kg Suc-HSA, given 15-30 min before the
      mice were challenged with the virus, sufficed to protect these mice against
      infection with the HIV-1 IIIB strain.

PMID- 9021052
TI  - The role of genotypic heterogeneity in wild type virus populations on the
      selection of nonnucleoside reverse transcriptase inhibitor-resistant viruses.
AB  - Virus populations were selected in cell culture using two widely used protocols
      in order to evaluate the role of selection methodology on the genotype and
      phenotype of nonnucleoside reverse transcriptase inhibitor resistant viruses.
      Selection was performed by serial passage of virus in the presence of gradually
      increasing concentrations of antiviral compound or passage in the presence of a
      constant high concentration of compound. Using the CEM-SS cell line, the IIIB
      strain of HIV-1, and identical nonnucleoside reverse transcriptase inhibitors,
      resistant viruses were obtained and their phenotypic and genotypic properties
      were defined. Resistant virus populations containing the Y181C amino acid change
      in the reverse transcriptase were predominantly selected with each of the tested
      compounds. Several of the compounds selected secondary amino acid changes using
      both methods. A comparison of the resistant viruses selected in our laboratory
      using each of the two protocols with viruses reported by a second laboratory
      employing one of the two methods suggests that genotypic differences in the
      selected virus isolates may most likely result from the variation in the genetic
      composition of the respective wild type virus pools, rather than the specific
      selection methodology employed. These results imply that HIV may select a wide
      variety of amino acid changes to avoid the inhibitory effects of the
      nonnucleoside reverse transcriptase inhibitors and the selection of compounds for
      clinical use in combination with agents possessing non-overlapping resistance
      phenotypes will require evaluation of the agents against virus isolates
      possessing each of the mutations known to confer drug resistance.

PMID- 9021053
TI  - Inhibition of herpes simplex virus replication by retinoic acid.
AB  - The retinoic acid (RA) isomers all-trans-RA, 9-cis-RA and 13-cis-RA as well as
      other retinoids were tested for their ability to reduce the yield of herpes
      simplex virus-1 (HSV-1). RA isomers reduced HSV-1 replication whereas the other
      retinoids, retinol, retinal, beta-carotene and amide derivatives of RA were not
      inhibitory. All-trans-RA reduced the yield of HSV-1 by 100-fold at 5
      micrograms/ml but 9-cis-RA and 13-cis-RA reduced viral replication by 10-fold. At
      a concentration of 10 micrograms/ml all-trans-RA and 9-cis-RA reduced virus yield
      by 1000-fold while 13-cis-RA decreased HSV-1 production by 100-fold. RA isomers
      at a concentration of 10 micrograms/ml were not cytotoxic for the Vero cells used
      in these studies. Immunofluorescence studies showed that all-trans-RA treated
      cell cultures exhibited small foci of virus specific immunostaining while
      untreated cultures displayed intense HSV-1 immunoreactivity in virtually the
      entire cell population. RA-dependent inhibition of HSV-1 replication required the
      presence of RA with the virus. HSV-1 replication proceeded when RA was removed
      from infected cells. Treatment of cell cultures with RA did not induce gene
      expression for type-1 interferon (IFN) or for the type-1 IFN inducible genes
      studied suggesting that RA inhibition of HSV-1 replication is not mediated by
      IFN. These studies have established the ability of RA to reduce the replication
      of HSV-1 in vitro.

PMID- 9021054
TI  - Monovalent and polymeric 5N-thioacetamido sialosides as tightly-bound receptor
      analogs of influenza viruses.
AB  - A possible approach to the development of synthetic inhibitors of influenza virus
      attachment to host cells is based on the anchoring of the minimum receptor
      determinant of influenza virus, sialic acid, to a polymeric carrier. In this
      study, the effect of substitution of oxygen by sulphur in the 5N-acetyl moiety of
      sialic acid on the binding of monovalent and polymeric sialosides by A and B
      influenza virus strains was investigated. The polymeric inhibitor with pendant 5N
      thioacetylneuraminic acid residues was found to be more broadly active against
      different virus stains that the one prepared from the Neu5Ac ligand.

PMID- 9021055
TI  - Nuclease stability as dominant factor in the antiviral activity of
      oligonucleotides directed against HSV-1 IE110.
AB  - The anti-herpes simplex virus type 1 (anti-HSV-1) efficacy of a series of
      oligonucleotides was determined as a function of their chemical structure. All
      oligonucleotides consisted of the same sequence directed against the translation
      initiation codon of the HSV-1 immediate early gene. The oligonucleotides were
      modified with phosphorothioate linkage patterns according to various protection
      strategies against nucleolytic degradation. We show that nuclease resistance is
      the dominant factor that determines the antiviral efficacy in this series. A
      minimal protection strategy, consisting of end-capping and pyrimidine protection,
      has proven to be particularly useful, because it not only yields nuclease
      resistant oligonucleotides but also minimizes non-sequence-specific effects.

PMID- 9021056
TI  - Case-based reasoning: opportunities and applications in health care.

PMID- 9021057
TI  - Combining a neural network with case-based reasoning in a diagnostic system.
AB  - This paper presents a new approach for integrating case-based reasoning (CBR)
      with a neural network (NN) in diagnostic systems. When solving a new problem, the
      neural network is used to make hypotheses and to guide the CBR module in the
      search for a similar previous case that supports one of the hypotheses. The
      knowledge acquired by the network is interpreted and mapped into symbolic
      diagnosis descriptors, which are kept and used by the system to determine whether
      a final answer is credible, and to build explanations for the reasoning carried
      out. The NN-CBR model has been used in the development of a system for the
      diagnosis of congenital heart diseases (CHD). The system has been evaluated using
      two cardiological databases with a total of 214 CHD cases. Three other well-known
      databases have been used to evaluate the NN-CBR approach further. The hybrid
      system manages to solve problems that cannot be solved by the neural network with
      a good level of accuracy. Additionally, the hybrid system suggests some solutions
      for common CBR problems, such as indexing and retrieval, as well as for neural
      network problems, such as the interpretation of the knowledge stored in a neural
      network and the explanation of reasoning.

PMID- 9021058
TI  - Case-based learning of plans and goal states in medical diagnosis.
AB  - We introduce a case-based system, BOLERO, that learns both plans and goal states.
      The major aim is that of improving the performance of a rule-based diagnosis
      system by adapting its behavior using the most recent information available about
      a patient. On the one hand BOLERO gets knowledge from cases in the form of
      diagnostic plans that are represented as sequences of decision steps. The
      advantages of this representation include: (1) retrieval and adaptation of parts
      of plans (steps) appropriate to the current problem state; (2) generation of new
      plans not previously available in memory; and (3) learning from experience, both
      from successful or failed plans. On the other hand, since goal states are sets of
      final diagnosis likelihoods they are not known beforehand, i.e. goal states are
      not defined and the system has to learn to recognize them. For this reason BOLERO
      has a case-based method that uses solutions of past cases to recognize a
      diagnostic state as a goal state of a new planning problem. BOLERO and a rule
      based system are integrated into a meta-level architecture in which we emphasize
      the collaboration of both systems in solving problems. The rule-based system
      executes the plans generated by BOLERO. As a consequence of the execution of
      plans, the rule-based system furnishes BOLERO with new information with which
      BOLERO can generate a new plan to adapt the reasoning process of the rule-based
      system into correspondence with the recent available data. All the methods have
      been designed to be useful for medical diagnosis and have been tested in the
      domain of diagnosing pneumonia.

PMID- 9021059
TI  - Feasibility analysis of a case-based reasoning system for automated detection of
      coronary heart disease from myocardial scintigrams.
AB  - Myocardial perfusion scintigraphy is a noninvasive diagnostic method for the
      evaluation of patients with suspected or proven coronary artery disease (CAD). We
      utilized case-based reasoning (CBR) methods to develop the computer-based image
      interpretation system SCINA which automatically derives from a scintigraphic
      image data set an assessment concerning the presence of CAD. We compiled a case
      library of 100 patients who underwent both perfusion scintigraphy and coronary
      angiography to document or exclude the presence of CAD. The angiographic
      diagnosis of the retrieved nearest neighbor match of a scintigraphic input case
      was selected as the CBR diagnosis. We examined the effects of input data
      granularity, case indexing, similarity metric, and adaptation on the diagnostic
      accuracy of the CBR application SCINA. For the final prototype, sensitivity and
      specificity for detection of coronary heart disease were 98% and 70% suggesting
      that CBR systems may achieve a diagnostic accuracy that appears feasible for
      clinical use.

PMID- 9021060
TI  - Retrieving cases for treatment advice in nursing using text representation and
      structured text retrieval.
AB  - A nursing database which records patient details and treatments as fields in a
      standard database format is transformed into a collection, in text form, of
      patient case days with history. Each case is represented as text strings encoding
      the patient details, the current problems, treatments and their associated
      history. The cosine measure of similarity is used to compute a whole case
      similarity between a text query and the cases in text form. This standard text
      retrieval technique is used and compared to a simple rule base. In case-based
      reasoning, the similarity of cases is often computed by combining similarities of
      the case features involved. In this work the standard text retrieval function is
      modified to incorporate this case structure by combining individual matches of
      case components based on the cosine measure. The combination is based on a linear
      regression model for learning the weights assigned to the components of this
      retrieval function. For the 1355 records two tasks were tried: predicting the
      treatment for a new problem and predicting the treatment for a continuing problem
      when a change of treatment is required. Simple text retrieval was better than the
      rule base for one task and case structured retrieval was at least 18% better on
      both tasks. Further techniques are discussed.

PMID- 9021065
TI  - Gestalten of today: early processing of visual contours and surfaces.
AB  - While much is known about the specialized, parallel processing streams of low
      level vision that extract primary visual cues, there is only limited knowledge
      about the dynamic interactions between them. How are the fragments, caught by
      local analyzers, assembled together to provide us with a unified percept? How are
      local discontinuities in texture, motion or depth evaluated with respect to
      object boundaries and surface properties? These questions are presented within
      the framework of orientation-specific spatial interactions of early vision. Key
      observations of psychophysics, anatomy and neurophysiology on interactions of
      various spatial and temporal ranges are reviewed. Aspects of the functional
      architecture and possible neural substrates of local orientation-specific
      interactions are discussed, underlining their role in the integration of
      information across the visual field, and particularly in contour integration.
      Examples are provided demonstrating that global context, such as contour closure
      and figure-ground assignment, affects these local interactions. It is illustrated
      that figure-ground assignment is realized early in visual processing, and that
      the pattern of early interactions also brings about an effective and sparse
      coding of visual shape. Finally, it is concluded that the underlying functional
      architecture is not only dynamic and context dependent, but the pattern of
      connectivity depends as much on past experience as on actual stimulation.

PMID- 9021066
TI  - The effects of cortical lesions on recognition of object context in a visuomotor
      task in the Mongolian gerbil.
AB  - Two experiments were carried out in order to determine the effects of either
      parietal or temporal lesions on performance in a depth vision task in which
      gerbils normally use retinal image size (RIS) as a cue to distance. In the first
      experiment, gerbils were trained to jump to two training targets that differed in
      size and which were always presented with distinctive local features and in a
      particular spatial location. After lesions, gerbils were presented with further
      training trials and sets of probe trials in which they were presented with
      targets that differed in width from the training targets, and sets of local
      features and distal cues that either matched or mismatched those presented during
      training. Shams and temporal animals made predictable over- or underjumps when
      local feature and distal information matched, and stopped using retinal image
      size when they did not match. Parietal animals did not use retinal image size
      either during the match or the mismatch conditions. In a second experiment,
      gerbils with parietal lesions were shown capable of using retinal image size in a
      simpler task that did not contain distinguishing local features or distal cues.
      Taken together, these results suggest that parietal lesions in gerbils disrupt
      object recognition, when the purpose of the recognition process is to complete a
      distance estimate for a visuomotor act.

PMID- 9021067
TI  - Neural substrates of discriminative avoidance learning and classical eyeblink
      conditioning in rabbits: a double dissociation.
AB  - In a previous study, lesions of the deep cerebellar nuclei blocked classical
      eyeblink conditioning, but did not impair discriminative avoidance learning in
      rabbits. Here, was also found previously, lesions of the anterior and medial
      dorsal thalamic nuclei severely impaired discriminative avoidance learning.
      However, these lesions had no impact on discriminative eyeblink conditioning or
      reversal learning. These results complete the demonstration of a double
      dissociation, indicating distinct neural substrates for the acquisition of these
      learned behaviors. It is proposed that the two learning circuits identified by
      these studies mediate, respectively, acquisition of specific adaptive reflexes
      and whole-body, voluntary goal-directed movements.

PMID- 9021068
TI  - Dissociable effects of AMPA-induced lesions of the vertical limb diagonal band of
      Broca on performance of the 5-choice serial reaction time task and on acquisition
      of a conditional visual discrimination.
AB  - The aim of the present study was to investigate the role of the cholinergic
      innervation of the cingulate cortex in visual attentional function and
      acquisition of a visual conditional discrimination task. Following AMPA (alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) lesions of the vertical limb
      diagonal band of Broca (VDB) which provides the main cholinergic projection to
      cingulate cortex, animals were not significantly impaired on the 5-choice serial
      reaction time task. This task, which provides a continuous performance test of
      visual attention, has previously been shown to be sensitive to AMPA lesions of
      the nucleus basalis magnocellularis (nbM). In contrast to the results obtained
      for visual attentional function, lesions of the VDB did significantly affect the
      acquisition of a visual conditional discrimination. While showing a significant
      facilitation in the early learning stage of acquiring this task animals with
      lesions of the VDB were significantly impaired during the late stages of learning
      this task. This late learning deficit was not the result of the animals being
      unable to learn the task due to the presence of the lesion throughout task
      acquisition as the results of a second experiment revealed that when animals were
      pre-trained to 70% accuracy on the task and then lesioned, the impairment in late
      learning was still apparent. In light of the results presented in the
      accompanying paper (Bussey et al., Behav. Brain Res., 1996), these results
      suggest that the early learning effects may be due to cholinergic denervation of
      the anterior cingulate cortex while the late learning effects may be due to
      denervation of the posterior cingulate cortex. Taken together with previous work
      indicating a role for the nbM cholinergic system in visual attentional function,
      these results suggest a role for the cholinergic innervation of the cingulate
      cortex in conditional learning but not for continuous attentional performance.

PMID- 9021069
TI  - Dissociable effects of anterior and posterior cingulate cortex lesions on the
      acquisition of a conditional visual discrimination: facilitation of early
      learning vs. impairment of late learning.
AB  - Two experiments investigated the effects of quinolinic acid induced lesions of
      the anterior and posterior cingulate cortices on the acquisition and performance
      of a conditional visual discrimination (CVD) task, in which rats were required to
      learn a rule of the type: "If lights are flashing FAST, press the right lever; if
      SLOW press left". In Experiment 1, animals with lesions of the anterior cingulate
      cortex (ANT group) demonstrated a significant enhancement in learning during the
      early stages of task acquisition. Conversely, animals with lesions of the
      posterior cingulate cortex (POS group) were impaired in learning during the later
      stages of acquisition. There were no significant differences between the ANT and
      POS groups on the performance of the task when either variable inter-trial
      intervals or reduced stimulus durations were imposed. In Experiment 2, the
      specificity of the lesion effects for processes operative during the early and
      late stages of learning was tested. Animals were trained to a criterion of 70%
      correct choices on two consecutive sessions prior to lesioning, and subsequently
      allowed to continue to acquire the task to the mean asymptotic performance level
      of 85% correct choices on two consecutive sessions. Animals of the POS group were
      impaired in learning during this later stage of task acquisition, thus
      replicating the pattern of results obtained in Experiment 1. The animals in
      Experiment 2 were then tested following a 30-day retention interval and during
      extinction (removal of sucrose from the magazine). The extinction test revealed
      an impairment in the ability of animals in the ANT group to omit lever responses
      in the absence of reinforcement. These results indicate that the anterior and
      posterior cingulate cortices are functionally dissociable, and suggest that they
      may form part of complementary, but competing, learning and memory systems.

PMID- 9021070
TI  - Kindling of hippocampal field CA1 impairs spatial learning and retention in the
      Morris water maze.
AB  - We used two procedures to assess the spatial learning and memory of rats in the
      Morris water maze task subsequent to kindling of hippocampal field CA1: (1)
      seizures were kindled with stimulation of CA1 prior to training in the water maze
      (acquisition); and (2) maze training was imposed until performance stabilized,
      seizures were kindled with stimulation of CA1, and then performance in the maze
      was reassessed (retention). In both conditions, behavioral testing occurred 24 h
      after the last kindled seizure. When the effects of CA1 kindling on acquisition
      were tested, we found that kindling of generalized seizures with stimulation of
      field CA1 (kindling), but not kindling of non-convulsive or partial seizures
      (partial kindling), produced deficits in the water maze. When the effects of CA1
      kindling on retention were tested, however, we found that kindling of either
      partial or generalized seizures produced deficits in the water maze. The results
      suggest that the processing of spatial information is vulnerable to the long
      lasting changes in neural excitability associated with kindling.

PMID- 9021071
TI  - Problem solving and logical reasoning in the macaque monkey.
AB  - This study focuses on the performances of monkeys in a spatial problem-solving
      task that involves working memory. Two monkeys had to find, by trial-and-error,
      the touching order of 2 or 3 targets in a set of 3 or 4 fixed spatial targets.
      When a solution was found and performed 6 times, the order was changed and the
      animal had to resume a new search within the same set of targets. Thus, in a
      training session, many searches (up to 60) could be initialised. The data show
      that the animals conducted a methodical search for the hidden order and found the
      solution in a minimal number of trials. We conclude that the monkey is able to
      construct complex cognitive structures, similar to logical reasoning, to solve
      spatial problems of this type.

PMID- 9021072
TI  - Object discrimination learning and object-pattern discrimination transfer in
      visually deprived cats.
AB  - We used binocularly deprived cats (BD cats), control cats reared in the
      laboratory with open eyes (C cats) and normal wild cats (N cats). In stage 1, the
      cats were trained to discriminate a black ping-pong ball and a 3-dimensional
      cross of the same size and color for food reward. The BD cats learned slower than
      N cats. The difference between BD cats and C cats was statistically
      insignificant. A comparison of these data and previous data on discrimination of
      corresponding 2-dimensional black patterns (disk and cross) show that in
      discrimination learning the 3-dimensionality of stimuli is helpful for N cats,
      but not for BD cats. Thus, the objects and their patterns are for BD cats highly
      similar. In stage 2, the objects were replaced by corresponding 2-dimensional
      patterns (disk and cross). Pattern discrimination was learned slower by BD cats
      than by N cats. Thus, the objects and their patterns are for BD cats certainly
      not identical and BD cats are deficient in discrimination transfer of even highly
      similar pairs of visual stimuli.

PMID- 9021073
TI  - Spatial memory deficits in segmental trisomic Ts65Dn mice.
AB  - Spatial memory was assessed in the segmental trisomic 16 mouse (Ts65Dn), a
      potential model for Down syndrome (DS), using the 12-arm radial maze (RAM).
      Ts65Dn mice have a portion of mouse chromosome 16 syntenic to the distal end of
      human chromosome 21 triplicated. On each of 8 daily trials of the RAM, Ts65Dn
      mice made fewer correct choices than control mice and performed at or near chance
      levels, indicating a deficit in spatial working memory. On trials 9 and 10,
      Ts65Dn mice performed as well as control mice on the initial 12 choices, but
      required a greater number of choices to complete the RAM. The improved
      performance of Ts65Dn mice on trials 9 and 10 was lost when the animals were
      retested after a 50-day retention period, suggesting that long-term memory is
      also defective. These results are not likely explained by differences in either
      response bias or perceptual discrimination. Ts65Dn and control mice displayed
      comparable levels of performance in spontaneous alternation in a T-maze,
      demonstrating that simple spatial memory was not impaired. In the elevated plus
      maze, Ts65Dn mice did not display higher anxiety levels which could affect their
      performance in the RAM. In fact, Ts65Dn mice visited open arms on the elevated
      plus maze more frequently and spent more time on open arms than did control mice.
      Taken together, these results provide evidence for short- and long-term spatial
      memory deficits in Ts65Dn mice.

PMID- 9021074
TI  - Comparison of site-specific injections into the basal forebrain on water maze and
      radial arm maze performance in the male rat after immunolesioning with 192 IgG
      saporin.
AB  - In this study, we investigated the effects of 192 IgG saporin injections into the
      medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined
      injections into the MSA and NBM, on water maze and radial arm maze performance in
      the male rat. The results of the present study reveal a dissociation between the
      effects of 192 IgG saporin injections into the basal forebrain on the performance
      of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG
      saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze
      performance when compared to controls. In contrast, injections of 192 IgG saporin
      into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task.
      Overall, the disruption of spatial learning observed in this study was, however,
      relatively mild compared to deficits in spatial learning reported using less
      selective lesions of the cholinergic basal forebrain. Consequently, the results
      of this study suggest that a selective reduction in cholinergic transmission in
      the basal forebrain is, by itself, insufficient to account for the functional
      impairments observed in spatial learning in the rat. Although our data do support
      the use of 192 IgG saporin as a selective cholinergic toxin in the basal
      forebrain, they further suggests that assessment of spatial learning in the rat
      following 192 IgG saporin lesions of the basal forebrain in combination with
      lesions to other neurotransmitter systems, may be a more viable approach to the
      elucidation of the neuropathological mechanisms that are associated with the
      cognitive deficits seen in Alzheimer's disease.

PMID- 9021075
TI  - Visual orienting and alerting in rhesus monkeys: comparison with humans.
AB  - The behavioral capacities of the rhesus monkey for several sensory and cognitive
      tasks appear quite similar to those of humans. To evaluate the monkey's
      attentional capacities, we have compared monkey and human performance on a
      visuospatial attentional task, the cued target detection (CTD) paradigm. Animals
      were trained to fixate a small spot of light while a cue and a subsequent target,
      are flashed in the visual periphery. In valid trials, the cue and target appeared
      in the same spatial location; in invalid trials, the cue and target appeared in
      the opposite location; in double trials, two cues were presented and the target
      appeared in one of their locations; in no-cue trials, the cue was omitted and the
      target appeared in one location. In addition, we varied cognitive control over
      the task initiation by making the trial onset either self-paced or computer
      paced. Reaction times (RTs) to target presentation, response accuracy, and
      frequency of aborted trials were measured for all subjects. No significant
      species differences were found for the patterns of RTs for different trial types
      or for attentional dynamics, as indexed by the decreases in RT with increasing
      cue-target interval. However, humans and non-human primates reacted differently
      to changes in cognitive control. Humans shows significant increases in no-cue
      trial RTs in the auto-paced task compared to the self-paced, but no differences
      in overall RT between tasks; monkeys showed a significant faster overall RT for
      the self-paced than the computer-paced task, but no difference between no-cue
      RTs. The performance differences between species may be related to the training
      history of the animals or to known anatomical differences in cortical
      organization, especially in the parietal lobe.

PMID- 9021076
TI  - Tuberomammillary nucleus lesion facilitates two-way active avoidance retention in
      rats.
AB  - To evaluate whether the tuberomammillary nucleus might be involved in the
      acquisition and/or retention of a two-way active avoidance conditioning, rats
      were given a unilateral lesion of the tuberomammillary nucleus (E2 region) 24 h
      prior to the first conditioning session. Four learning sessions were performed:
      one acquisition and 3 retention sessions (short-term, 24 h; and long-term, 8 and
      18 days). Results showed that the lesion facilitated the long-term retention of
      conditioning, but no effects were observed on acquisition and short-term
      retention. Since rewarding intracranial electrical stimulation seems to be a
      consistent way to facilitate learning and memory processes, and tuberomammillary
      lesion has been shown to improve intracranial self-stimulation behavior (ICSS),
      we suggest that lesions in the present experiment could have facilitated two-way
      active avoidance retention by enhancing the function of brain reward mechanisms.

PMID- 9021105
TI  - A more rational basis for determining the activities used for radionuclide
      imaging?

PMID- 9021106
TI  - Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine
      D2 receptor images in schizophrenia.
AB  - This paper describes the application of a multivariate statistical technique to
      investigate striatal dopamine D2 receptor concentrations measured by iodine-123
      iodobenzamide (123I-IBZM) single-photon emission tomography (SPET). This
      technique enables the automatic segmentation of dynamic nuclear medicine images
      based on the underlying time-activity curves present in the data. Once the time
      activity curves have been extracted, each pixel can be mapped back on to the
      underlying distribution, considerably reducing image noise. Cluster analysis has
      been verified using computer simulations and phantom studies. The technique has
      been applied to SPET images of dopamine D2 receptors in a total of 20 healthy and
      20 schizophrenic volunteers (22 male, 18 female), using the ligand 123I-IBZM.
      Following automatic image segmentation, the concentration of striatal dopamine D2
      receptors shows a significant left-sided asymmetry in male schizophrenics
      compared with male controls. The mean left-minus-right laterality index for
      controls is -1.52 (95% CI -3.72-0.66) and for patients 4.04 (95% CI 1.07-7.01).
      Analysis of variance shows a case-by-sex-by-side interaction, with F=10.01, P=0.
      005. We can now demonstrate that the previously observed male sex-specific D2
      receptor asymmetry in schizophrenia, which had failed to attain statistical
      significance, is valid. Cluster analysis of dynamic nuclear medicine studies
      provides a powerful tool for automatic segmentation and noise reduction of the
      images, removing much of the subjectivity inherent in region-of-interest
      analysis. The observed striatal D2 asymmetry could reflect long hypothesized
      disruptions in dopamine-rich cortico-striatal-limbic circuits in schizophrenic
      males.

PMID- 9021107
TI  - Initial evaluation of 123I-5-I-R91150, a selective 5-HT2A ligand for single
      photon emission tomography, in healthy human subjects.
AB  - The mapping of 5-HT2 receptors in the brain using functional imaging techniques
      has been limited by a relative lack of selective radioligands. Iodine-123
      labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-io do
      2-methoxybenzamide (123I-5-I-R91150 or 123I-R93274) is a new ligand for single
      photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A
      receptors. This study reports on preliminary 123I-5-I-R91150 SPET, whole-body and
      blood distribution findings in five healthy human volunteers. Maximal brain
      uptake was approximately 2% of total body counts at 180 min post injection (p.i.
      ). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice
      multi-detector system SME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.)
      was seen in the cerebellum, a region free from 5HT2A receptors. In contrast,
      radioligand binding in the frontal cortex increased steadily over time, up to a
      peak at approximately 100-120 min p.i. Frontal cortex-cerebellum activity ratios
      reached values of 1.4, and remained stable from approximately 100 min p.i.
      onwards. Multi-slice SPET sequences showed a pattern of regional variation of
      binding compatible with the autoradiographic data on the distribution of 5-HT2A
      receptors in humans (cerebral cortex>striatum>cerebellum). These findings suggest
      that 123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the
      living human brain with SPET.

PMID- 9021108
TI  - Detection of acute inhalation injury in fire victims by means of technetium-99m
      DTPA radioaerosol inhalation lung scintigraphy.
AB  - Mortality and morbidity in fire victims are largely a function of injury due to
      heat and smoke. While the degree and area of burn together constitute a reliable
      numerical measure of cutaneous injury due to heat, as yet no satisfactory measure
      of inhalation injury has been developed. In this study, we employed technetium
      99m diethylene triamine penta-acetic acid (DTPA) radioaerosol lung scintigraphy
      (inhalation scan) to evaluate acute inhalation injury in fire victims. Ten normal
      controls and 17 survivors from a fire accident were enrolled in the study. All
      patients suffered from respiratory symptoms (dyspnoea and/or cough with sputum).
      99mTc-DTPA aerosol inhalation lung scintigraphy was performed in all subjects,
      using a commercial lung aerosol delivery unit. The degree of lung damage was
      presented as the clearance rate (k; %/min) calculated from the time-activity
      curve over the right lungs. In addition, the distribution pattern of the
      radioactivity in the lungs was evaluated and classified into two groups:
      homogeneous distribution and inhomogeneous distribution. A plain chest radiograph
      (CxR) and pulmonary function test (PFT) were performed in the same group of
      patients. The results showed that 6/17 (35.3%) patients had inhomogeneous
      distribution of radioactivity in their inhalation scans, and 11/17 (64.7%) had
      homogeneous scans. Five of the six patients with inhomogeneous scans were
      admitted for further management, and all patients with homogeneous scans were
      discharged from the emergency department and needed no further intensive care.
      The clearance rates of the right lung were 0.73%+/-0.13%/min for normal controls
      and 1.54%+/-0.58%/min for fire victims. The difference was significant, with a P
      value of less than 0.01. Using a cut-off value of 0.9%/min (all normal subjects
      were below 0. 9%/min), 14 (82.4%) patients had abnormal clearance rates of 99mTc
      DTPA from the lung. In contrast, only three (17.6%) patients had abnormal CxR and
      three (17.6%) had abnormal PFTs. We conclude that (1) conventional CxR and PFT
      are not good modalities for evaluating inhalation injury in fire victims because
      of their low sensitivity, and (2) 99mTc-DTPA radioaerosol inhalation scintigraphy
      can provide an objective evaluation of inhalation injury during a fire accident
      and may be useful in therapeutic decision-making and disease monitoring.

PMID- 9021109
TI  - Compartmental analysis of asialoglycoprotein receptor scintigraphy for
      quantitative measurement of liver function: a multicentre study.
AB  - A multicentre study on multicompartmental analysis of hepatic scintigraphy using
      technetium-99m labelled galactosyl serum albumin (GSA), which binds to the
      asialoglycoprotein receptor, was carried out at seven institutions in Japan.
      Seventy-four patients with liver disease received 3 mg (185 MBq) of 99mTc-GSA by
      intravenous injection. Sequential scanning was performed 30 min after injection
      to obtain anterior images of the heart and liver, followed by single-photon
      emission tomography (SPET). The indices included in this analysis were hepatic
      blood flow (Q) and maximal receptor binding rate (Rmax), which showed a good
      correlation with semiquantitative ratio indices for 99mTc-GSA, namely the
      retention rate in blood (HH15) and the hepatic uptake rate (LHL15). Q and Rmax
      also showed a significant correlation with other measures of hepatic function.
      When patients were grouped according to the severity of chronic liver damage
      (hepatocellular functional damage), Q was reduced in the moderate and severe
      groups, while Rmax was reduced in proportion to the functional stage. Both
      parameters showed no inter-institution difference using analysis of co-variance
      with the functional stage as a co-variant. With regard to the hepatic uptake
      rate, anterior planar images and SPET images gave similar results for Q and Rmax.
      Acquisition times of 15 or 30 min provided the same results. The
      multicompartmental model analysis permitted comparable results to be obtained at
      institutions using different gamma cameras, and is therefore considered a
      universally applicable method. These results indicate that Q and Rmax are useful
      general indices for evaluating the functional reserve capacity of the liver.

PMID- 9021110
TI  - Auxiliary liver transplantation in patients with fulminant hepatic failure:
      hepatobiliary scintigraphic follow-up.
AB  - Auxiliary liver transplantation (ALT), retaining in place the liver of the
      recipient, has been proposed as an alternative to liver replacement in patients
      with fulminant hepatic failure (FHF). Hepatobiliary scintigraphy (HS) has proved
      a unique tool for the separate assessment of graft and native liver function.
      Forty-eight HS scans were performed, following the injection of technetium-99m
      trimethyl-bromo-imino-diacetic acid, in six patients who underwent ALT for FHF.
      Quantitative parameters were derived from the time-activity curves of both the
      graft and the native liver. The function of the graft remained normal as long as
      the patients remained under immunosuppressive therapy (IST). The function of the
      native liver was almost completely absent in the 1st month in five patients, but
      it improved gradually in four of them. IST was then decreased in four patients
      and finally withdrawn in three. Spontaneous graft atrophy occurred in two
      patients and the graft was removed in two. All of the patients in whom IST was
      reduced had a normal global hepatic function and selective uptake (RU) >30% at
      that time. In ALT patients with FHF, HS can distinguish non-invasively the
      functional performance of both the donor and the recipient liver and its
      evolution with time.

PMID- 9021111
TI  - Comparison and histopathological correlation of three parathyroid imaging methods
      in a population with a high prevalence of concomitant thyroid diseases.
AB  - The aim of this prospective study was to evaluate the diagnostic utility of a
      technetium-99m sestamibi dual-phase protocol enhanced by single-photon emission
      tomography (SPET) and semiquantitative analysis in comparison to established
      preoperative staging procedures in patients with primary hyperparathyroidism.
      Twenty-eight (50%) out of 56 patients had superimposed thyroid disease, and 12
      patients had previously undergone neck surgery. Visual and semiquantitative
      analysis of planar 99mTc-sestamibi dual-phase imaging, SPET of the delayed phase,
      ultrasonography, and thallium-201 chloride-technetium-99m pertechnetate
      subtraction scintigraphy was further correlated with the histopathological
      examination of the surgical specimens. 99mTc-sestamibi dual-phase imaging
      achieved the highest sensitivity for side localization and precise localization
      compared with 201Tl-99mTc subtraction scintigraphy and ultrasonography, but the
      differences reached statistical significance only in comparison to
      ultrasonsography. Semiquantitative analysis did not enhance sensitivity. Adenoma
      detection by 99mTc-sestamibi dual-phase imaging was only correlated to serum
      calcium levels and osteocalcin, not to cell density or oxyphil cell count (SPET
      yielded additional information for the exact topographical localization of the
      parathyroid tumour in 22 (39%) patients with superimposed thyroid disease or
      previous neck surgery but did not enhance the overall detection rate.

PMID- 9021112
TI  - In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m
      sestamibi scan in untreated breast cancer patients.
AB  - Technetium-99m sestamibi is a transport substrate recognised by the multidrug
      resistant P-glycoprotein (Pgp). To test whether 99mTc-sestamibi efflux is
      enhanced in breast carcinomas overexpressing Pgp, we determined the efflux rates
      of 99mTc-sestamibi and Pgp levels in tumours from 30 patients with untreated
      breast carcinoma. Patients were intravenously injected with 740 MBq of 99mTc
      sestamibi and underwent a 15-min dynamic study followed by the acquisition of
      static planar images at 0.5, 1, 2 and 4 h. Tumour specimens were obtained from
      each patient 24 h after 99mTc-sestamibi scan and Pgp levels were determined using
      125I-MRK16 monoclonal antibody and in vitro quantitative autoradiography. All
      breast carcinomas showed high uptake of 99mTc-sestamibi and data from region of
      interest analysis on sequential images were fitted with a monoexponential
      function. The efflux rates of 99mTc-sestamibi, calculated from decay-corrected
      time-activity curves, ranged between 0.00121 and 0.01690 min-1 and were directly
      correlated with Pgp levels measured in the same tumours (r=0.62; P<0.001). Ten
      out of 30 breast carcinomas (33%) contained 5 times more Pgp than benign breast
      lesions and showed a mean concentration of 5.73+/- 1.63 pmol/g of tumour (group
      A). The remaining 20 breast carcinomas had a mean Pgp concentration of 1.29+/
      0.64 pmol/g (group B), equivalent to that found in benign breast lesions. 99mTc
      sestamibi efflux from tumours of group A was 2.7 times higher than that observed
      in tumours of group B (0.00686+/-0.00390 min-1 vs 0.00250+/-0.00090 min-1,
      P<0.001). The in vivo functional test with 99mTc-sestamibi showed a sensitivity
      and a specificity of 80% and 95%, respectively. In conclusion, the efflux rate of
      99mTc-sestamibi may be used for the in vivo identification of the multidrug
      resistant (MDR1) phenotype in untreated breast cancer patients.

PMID- 9021113
TI  - ECG-manifest and ECG-silent dipyridamole technetium-99m sestamibi SPET perfusion
      defects in patients with ischaemic heart disease.
AB  - At dipyridamole myocardial scintigraphy, perfusion defects are seldom backed up
      by significant ECG changes. This would suggest myocardial blood flow
      heterogeneity, rather than true ischaemia, as the cause of the scintigraphic
      abnormalities. Electrocardiographic surface mapping has been documented to be
      more accurate than standard 12-lead ECG in the detection of provoked ischaemia.
      Thus, to investigate the relationship between ECG changes and perfusion
      abnormalities, body surface maps were recorded during dipyridamole infusion in 55
      subjects (11 normals and 44 patients with ischaemic heart disease) undergoing
      dipyridamole technetium-99m sestamibi single-photon emission tomography (SPET).
      All had a normal resting ECG. The extent and severity of the sestamibi defect
      were quantified. New negative areas in the isointegral maps and rest-dipyridamole
      map differences >2 SD from normal limits were considered abnormal. After
      dipyridamole in normals, neither perfusion defects nor >/=1 mm ST segment
      depression on 12-lead ECG nor new negative areas in isointegral maps occurred. In
      patients, dipyridamole induced new perfusion defects in 35 (80%) but ST segment
      depression in only 18 (41%, P<0.001). Of the 35 patients with perfusion defects,
      17 (49%, group 1) showed ST segment depression, while the other 18 (51%, group 2)
      did not. Abnormal body surface maps were found in 100% of group 1 and 88% of
      group 2 patients (NS). In group 1, the provoked hypoperfusion was of greater
      extent (P=0.007) and severity (P=0.01) and the onset of map abnormalities was
      significantly earlier (P<0. 001) than in group 2; time to map abnormalities was
      also significantly shorter than time to ST segment depression (P=0.01). In the 35
      patients with complete scintigraphic, body map and angiographic data, the
      severity of reversible perfusion defect proved to be the strongest correlate of
      ST segment depression upon logistic regression analysis. Thus, sestamibi SPET
      abnormalities after dipyridamole are almost always associated with electrical
      changes on body surface maps, suggesting myocardial ischaemia as their cause. The
      much less common 12-lead ECG changes are slower to appear and reflect a more
      severe hypoperfusion.

PMID- 9021114
TI  - Metabolic myocardial viability assessment with iodine 123-16-iodo-3
      methylhexadecanoic acid in recent myocardial infarction: comparison with thallium
      201 and fluorine-18 fluorodeoxyglucose.
AB  - The best test presently available to ascertain residual viability within an
      infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to
      detect the persistence of some cellular metabolism. Rest reinjection of thallium
      201 is a less accurate alternative but is easy to perform. Iodinated fatty acids,
      which are used with standard gamma cameras, are proposed as markers of cellular
      metabolism. This study was performed to assess the value of 16-iodo-3
      methylhexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by
      comparison with FDG in patients with a recent myocardial infarction, and to
      evaluate its contribution compared with the 201Tl stress-redistribution
      reinjection technique. Stress-redistribution-reinjection 201Tl imaging, rest MIHA
      imaging and glucose-loaded FDG imaging were performed in 22 patients with recent
      myocardial infarction. Out of the 628 myocardial segments obtained from the left
      ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum
      uptake on stress 201Tl imaging), 177 of which were severely hypoperfused
      (relative uptake <0.50). Receiver operating characteristic (ROC) curves for
      predicting metabolic myocardial viability with FDG were derived from the results
      in respect of (a) 201Tl activity during exercise, redistribution and reinjection
      and (b) MIHA uptake, using the two FDG thresholds most commonly considered to
      define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused
      segments demonstrated that 201Tl reinjection was the most accurate test in
      predicting the presence of myocardial viability (area under the ROI curves=0.85
      and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively; P<0.05 vs other
      tests). The global predictive values of MIHA and 201Tl reinjection were,
      respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at
      the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments
      were considered, 201Tl reinjection remained the most accurate test (accuracy 0.84
      at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy
      of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the
      0.60 FDG threshold, P<0.05 vs 201Tl reinjection). In all circumstances, MIHA was
      less specific than 201Tl reinjection for the detection of metabolic viability. In
      conclusion, in patients with recent myocardial infarction, MIHA accurately
      detects the persistence of metabolic viability, but is not superior to 201Tl.

PMID- 9021115
TI  - The occurrence of false-positive technetium-99m sestamibi bull's eye defects in
      different reference databases. A study of an age- and gender-stratified healthy
      population.
AB  - Myocardial perfusion single-photon emission tomographic (SPET) imaging has been
      shown to be sensitive in the detection of coronary artery disease (CAD), whereas
      its specificity has been suboptimal. The aim of the present study was to study
      the frequency of abnormal bull's eye perfusion defects in a large age-stratified
      group of healthy subjects undergoing myocardial SPET assessed by comparison with
      two existing commercially available reference databases. One hundred and twenty
      eight healthy volunteers (76 males and 52 females) with a less than 5% likelihood
      of CAD underwent rest and exercise technetium-99m sestamibi SPET. The false
      positive response rate, defined as a significant reversible defect, was 12% when
      compared to the CEqual database and 29% when compared to the Cedars-Sinai
      database. With the CEqual program, rest defects occurred in 12% of the subjects.
      Defects occurred more often in women than in men, but the difference did not
      attain statistical significance. Significant defects were most frequent in the
      inferior wall and in women in the anterior wall as well. The distribution of
      defects was independent of age. Our results suggest that the specificity of 99mTc
      sestamibi myocardial SPET using commercially available reference files is
      suboptimal. The risk of obtaining a false-positive test result in subjects
      undergoing 99mTc-sestamibi myocardial SPET with a very low likelihood of CAD was
      higher than anticipated. With both reference files false-positive test results
      were most frequently observed in the inferior wall. Our data suggest that
      commercial reference files for myocardial SPET need to be optimised, and should
      be used with caution. The use of attenuation correction may prove to be a major
      step forward.

PMID- 9021116
TI  - Enhanced bilateral somatostatin receptor expression in mediastinal lymph nodes
      ("chimney sign") in occult metastatic medullary thyroid cancer: a typical site of
      tumour manifestation?
AB  - In medullary thyroid cancer (MTC), post-surgically elevated plasma calcitonin
      and/or carcinoembryonic antigen levels frequently indicate persisting metastatic
      disease, although conventional diagnostic procedures fail to localize the
      responsible lesions (occult disease). Somatostatin analogues have been used
      successfully in disease localization, but recently concerns have been raised that
      increased thoracic uptake of indium-111 pentetreotide in patients with previous
      external beam irradiation may represent a false-positive finding, caused by post
      irradiation pulmonary fibrosis. We recently examined seven patients with
      metastatic MTC by somatostatin receptor scintigraphy (six with occult and one
      with established disease). In four patients, all of whom had stable or slowly
      rising tumour marker levels over several years, a chimney-like bilateral
      mediastinal uptake of indium-111 pentetreotide was found. In two patients with
      persisting hypercalcitonaemia immediately after primary surgery, supraclavicular
      lymph node metastases were identified as the responsible lesions. None of these
      seven patients had prior external beam radiation therapy. In two cases,
      histological confirmation was obtained. In one patient, disease progression could
      be shown during follow-up. These data suggest that bilateral mediastinal lymph
      node involvement is a typical site of disease in slowly progressing occult
      metastatic MTC; the "chimney sign" may represent a typical finding with
      somatostatin analogues in such cases. Therefore, we believe that even in the case
      of prior external beam irradiation, mediastinal uptake of octreotide might
      represent metastatic MTC rather than radiation fibrosis.

PMID- 9021117
TI  - Breast cancer staging using technetium-99m sestamibi and indium-111 pentetreotide
      single-photon emission tomography.
AB  - We evaluated the clinical usefulness of single-photon emission tomography (SPET)
      with technetium-99m sestamibi and indium-111 pentetreotide in breast cancer
      staging. Fifteen patients with clinical and/or mammographic findings suggesting
      T1-2N0-1 breast cancer were studied. SPET images were acquired 20 min after 99mTc
      sestamibi injection and 4 and 24 h after 111In-pentetreotide injection. Patients
      underwent surgery the day after the later 111In-pentetreotide acquisition.
      Pathological examination showed 16 tumours in the 15 patients, with one bilateral
      carcinoma. The mean tumour diameter was 18.7 mm. Metastatic axillary involvement
      was found in 6/16 tumours, with a mean of five metastatic nodes per axilla. Both
      tracers correctly identified 15/16 primary tumours and five of the six cases of
      metastatic axillary node involvement. No difference between the tracers was
      observed in breast cancer staging. 99mTc-sestamibi seems to be the better tracer
      in terms of physical characteristics, execution time and cost-effectiveness. Our
      data suggest the future possibility of using nuclear medicine imaging to avoid
      axillary dissection in patients with T1 breast cancer.

PMID- 9021118
TI  - Localization of ectopic parathyroid glands using technetium-99m sestamibi
      imaging: comparison with magnetic resonance and computed tomographic imaging.
AB  - The aim of the study was to compare the accuracy of technetium-99m sestamibi
      imaging for localization of ectopic parathyroid glands in patients with
      hyperparathyroidism with that of magnetic resonance (MR) and computed tomographic
      (CT) imaging. Eleven patients with primary (n=3) or secondary (n=8)
      hyperparathyroidism were studied with 99mTc sestamibi parathyroid imaging CT and
      MR imaging. Images of the neck were acquired at 10 min and 2-3 after tracer
      injection. The three patients with primary hyperparathyroidism and five patients
      with secondary hyperparathyroidism underwent parathyroidectomy. The ectopic
      glands were confirmed by histopathological examination of the resected specimens.
      In respect of 20 parathyroid glands in the eight patients explored surgically,
      the sensitivity and specificity of sestamibi imaging were 70% (14/20) and 88%,
      respectively, those of CT, 40% (8/20) and 88%, and those of MR imaging, 60%
      (12/20) and 88%. Of these patients, three had parathyroid adenomas while five had
      hyperplasia (17 glands). Sestamibi imaging localized eight ectopic parathyroid
      glands, which were surgically confirmed (six were located in the thymus and two
      in the mediastinum). In one patient explored surgically, the ectopic gland was
      located outside the field of the MR coil. Although the remaining three cases of
      secondary hyperparathyroidism were not confirmed surgically, these patients
      demonstrated sestamibi uptake in five parathyroid glands, including three ectopic
      glands. MR images demonstrated abnormal parathyroid glands in the same regions as
      sestamibi imaging. Our data indicate that 99mTc-sestamibi imaging should be used
      initially to localize the ectopic parathyroid glands in patients with
      hyperparathyroidism for anatomical guidance prior to MR or CT imaging.

PMID- 9021119
TI  - Bone mineral density and bone scintigraphy in children and adolescents with
      osteomalacia.
AB  - In order to demonstrate the role of bone mineral density (BMD) measurement and
      bone scans in the management of patients with osteomalacia, radioisotope bone
      scintigraphy using technetium-99m methylene diphosphonate (MDP) and BMD
      measurements of the lumbar spine and femur by means of dual X-ray absorptiometry
      (DXA) were performed at the time of diagnosis and 6 months after therapy in 26
      Saudi patients (17 females and nine males). Their mean age was 13.5 years (range,
      5-16). BMD measurements were compared with those of normal Saudi subjects matched
      for age and sex. Bone scan showed an increase in tracer uptake throughout the
      skeleton ("superscan") in all children and demonstrated multiple stress fractures
      in eight. The mean BMD for the lumbar spine was 0.53 g/cm2 (Z-score, -3.1) and
      for the femoral neck 0.55 g/cm2 (Z-score, -2.8). Repeated bone scan and BMD after
      6 months of therapy with oral vitamin D, calcium and proper sun exposure
      demonstrated a significant increase (P<0.001) in BMD and healing of
      pseudofractures. In conclusion, as a non-invasive method with minimal radiation
      exposure, measurements of BMD in children with osteomalacia are to be recommended
      in the initial assessment of the severity of osteopenia and in the follow-up to
      monitor the response to therapy. Bone scintigraphy is valuable in demonstrating
      the site and severity of stress fractures.

PMID- 9021120
TI  - The effect of circulating antigen on the biodistribution of the engineered human
      antibody hCTM01 in a nude mice model.
AB  - Clinical studies are currently underway to assess the biodistribution and
      therapeutic potential of the genetically engineered human antibody hCTM01
      directed against polymorphic epithelial mucin (PEM) in patients with ovarian
      carcinoma. The present study was undertaken to assess the effect of circulating
      PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1
      transfected adenocarcinoma cell lines. Tumour xenografts were established from
      three cell lines: 413-BCR, which expressed antigen on the cell surface and also
      shed antigen into the circulation, E3P23, which expressed the antigen but did not
      shed into the circulation, and a negative control (410.4 MUCI). Groups of five
      mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then
      sacrificed, followed by assay of tissue uptake. The results showed a clear
      difference in the tumour and liver uptake, with the non-secreting cell line
      showing almost twice the tumour uptake and approximately 20% of the liver uptake
      of the secreting cell line.

PMID- 9021121
TI  - Impaired coronary circulation in acute myocardial infarction: a dipyridamole
      thallium-201 study.
AB  - Coronary flow reserve is not fully restored immediately after revascularization
      of an occluded vessel. The present study examined the coronary flow impairment in
      patients with acute myocardial infarction (AMI) after successful balloon
      angioplasty or spontaneous recanalization (without residual epicardial coronary
      stenosis). Fourteen patients underwent thallium-201 dipyridamole scintigraphy in
      the acute phase (mean 5.9 days) and in the chronic phase (mean 24. 6 days) after
      AMI. A 201Tl reinjection study was carried out only in the acute phase of AMI.
      The fill-in phenomenon was assessed by the %201Tl uptake in the infarct region
      after 201Tl reinjection, and positive (n=8) and negative (n=6) fill-in groups
      were distinguished. The %201Tl uptake increased from the acute phase study to the
      chronic phase study in the positive fill-in group (56.1%+/-4.1% to 74.4%+/-13.6%,
      P<0.001), whereas it decreased in the negative fill-in group (54.0%+/-10.6% to
      43.7%+/-9.9%, P<0.05). The change in %201Tl uptake following reinjection was
      significantly correlated with the improvement in regional ventricular wall motion
      in the chronic phase (r=0.85, P<0.001). We conclude that the impaired coronary
      flow reserve persisted after balloon angioplasty or spontaneous recanalization,
      which might indicate the presence of "microvascular stunning". The increase in
      %201Tl uptake predicted the change in ventricular wall motion.

PMID- 9021122
TI  - Regional cerebral perfusion in cardiovascular reflex syncope.
AB  - Little is known about the regional cerebral perfusion in subjects with presyncope
      or syncope, and the impact that autonomic nervous dysfunction has on it. Seven
      subjects with cardiovascular vasodepressor reflex syncope were studied. A
      baseline test was performed with the patients standing in the 70 degrees upright
      position, while the passive head-up tilt table test with and without isoprenaline
      infusion was employed for provocation. Regional cerebral perfusion was assessed
      by means of single-photon emission tomography with technetium-99m labelled V-oxo
      1,2-N, N1-ethylenedylbis-l-cysteine diethylester (baseline, and during blood
      pressure decline in the provocation test) and the autonomic nervous function by
      means of spectral analysis of heart rate variability (baseline, and before blood
      pressure decline in the provocation test). Every subject showed an abrupt decline
      in blood pressure in the provocation test (five with presyncope and two with
      syncope). The systolic and diastolic blood pressures decreased significantly
      (P<0.001) between the baseline and the provocation study time points
      (radiopharmaceutical injection and lowest systolic blood pressure). Mean cerebral
      perfusion as average count densities decreased upon provocation as compared with
      baseline (190+/-63 vs 307+/-90 counts/voxel, respectively, P=0.013).
      Hypoperfusion was most pronounced in the frontal lobe. These results suggest that
      cerebral perfusion decreases markedly during presyncope or syncope with systemic
      blood pressure decline in subjects with cardiovascular vasodepressor syncope.
      Furthermore, the autonomic nervous function remains unchanged before the systemic
      blood pressure decline.

PMID- 9021123
TI  - Highlights of the annual meeting of the European Association of Nuclear Medicine:
      Copenhagen 1996. Nuclear medicine 100 years after the discovery of radioactivity.

PMID- 9021124
TI  - Mutations in SPK1/RAD53 that specifically abolish checkpoint but not growth
      related functions.
AB  - SPK1/RAD53/SAD1/MEC2 encodes an essential protein kinase of Saccharomyces
      cerevisiae and is required for the execution of checkpoint arrest at multiple
      stages of the cell cycle. We have isolated two mutant alleles of SPK1 (spk1K227A
      and spk1-1A208P) that are defective for checkpoint-arrest functions but retain
      wild-type levels of SPK1-associated growth activity. Both mutations occur within
      conserved regions of the kinase domain of SPK1 resulting in a substantial
      reduction in the catalytic activity of Spk1. Thus, while minimal levels of Spk1
      kinase activity are capable of supporting normal rates of growth, higher levels
      are required for checkpoint functions. In addition, using deletional analysis we
      have identified a region within the N-terminus of Spk1 outside of the conserved
      kinase domain that is required for checkpoint functions. Interestingly, this
      region may be important in the regulation of Spk1 kinase activity.

PMID- 9021125
TI  - Deletion of flanking ARS elements does not affect meiotic recombination at the
      HIS4 locus in yeast.
AB  - The HIS4-BIK1 interval on chromosome III of Saccharomyces cerevisiae contains a
      hotspot for meiotic recombination. Previous reports demonstrated that the
      initiating lesion is a double-stranded break which is subsequently processed in
      an asymmetric manner. Data presented here show that the efficiency of initiation
      of meiotic recombination is unaffected by the deletion of flanking ARS elements,
      and that the distribution of recombinants is not altered in strains heterozygous
      for these deletions. These results suggest that the initiation of recombination
      is not affected by the time of replication of the hotspot at HIS4. The data also
      indicate that altering the direction of replication-fork movement through the
      HIS4 region does not affect meiotic recombination.

PMID- 9021126
TI  - Heat-shock response in Schizosaccharomyces pombe cells lacking cyclic AMP
      dependent phosphorylation.
AB  - Heat sensitivity at 48 degrees C was determined in log-phase cultures of control
      and pka1-disrupted cells of the fission yeast Schizosaccharomyces pombe grown at
      25 degrees C. Cells devoid of protein kinase A exhibited a considerable heat
      shock resistance as compared to control cells. Addition of cAMP to control cells
      prompted a further decrease in viability during heat shock. This effect was not
      observed with pka1-disrupted cells, suggesting that cAMP-dependent
      phosphorylation is involved in modulation of the heat-shock response. When
      control or pka1-disrupted cells were grown at 25 degrees C and then shifted to 37
      degrees C they acquired thermo-tolerance to a subsequent treatment at 48 degrees
      C both in the absence and in the presence of exogenous cAMP. Inhibition of
      protein synthesis during the adaptive treatment did not block the development of
      thermo-tolerance. However, the arrest in translation significantly prevented
      trehalose accumulation in control cells but only slightly affected trehalose
      increase in pka1-disrupted cells. These data indicate that heat resistance may be
      established in growing cells of S. pombe by at least two independent post
      translational mechanisms: a decrease in cAMP-dependent protein phosphorylation
      and a hitherto unknown process which may be independent of trehalose
      accumulation.

PMID- 9021128
TI  - Structural analysis of a Candida glabrata centromere and its functional homology
      to the Saccharomyces cerevisiae centromere.
AB  - A 451-bp fragment exhibiting centromere activity had been previously isolated
      from Candida glabrata genomic DNA. It contains three elements, CgCDEI, CgCDEII
      and CgCDEIII, highly homologous to those of Saccharomyces cerevisiae. In this
      study, the requirement of each element for centromere function was analyzed in
      detail. Deletion analysis identified a small fragment of 153 bp, which included
      all three elements, to be sufficient for centromere activity. Linker substitution
      analysis of CgCDEI and CgCDEIII revealed that both elements are required for
      centromere function. Some of the substitution mutations in CgCDEIII caused a
      complete loss of centromere activity. These results suggested a functional
      similarity of centromeres between C. glabrata and S. cerevisiae. However, the C.
      glabrata centromere did not function in S. cerevisiae cells, suggesting species
      specificity of the C. glabrata centromere. To examine whether species specificity
      of the centromeres between these two yeasts does exist, chimeric centromeres
      between the two species were constructed. Exchange of CgCDEII or CgCDEIII with
      CDEII or CDEIII of S. cerevisiae, respectively, increased C. glabrata centromere
      activity in S. cerevisiae, indicating participation of the two elements in
      determining the species specificity of centromere function.

PMID- 9021127
TI  - Identification of a Saccharomyces cerevisiae mitochondrial-DNA which can act as a
      promoter tightly regulated by carbon source when placed in the nucleus.
AB  - Screening of a promoter probe gene bank for DNA sequences that could act as
      inducible promoters following growth on non-fermentable carbon sources led to the
      identification of the mitochondrially encoded cytochrome oxidase subunit 1 gene
      (COX1) as an active sequence. Carbon-source regulation of this promoter was
      confirmed by a beta-galactosidase assay which showed a 31- and 180-fold induction
      of expression after growth on ethanol or lactate-based media respectively. Two
      elements matching the CCAAT-binding-factor motif, which is involved in activating
      transcription on non-fermentable carbon sources, were identified in the putative
      promoter. Expression was found to be reduced to low levels in otherwise isogenic
      hap3 and hap4 mutant strains. Thus, this mitochondrial DNA when placed in the
      nucleus can act as a promoter that is subject to strict carbon-source regulation.
      These observations are discussed both with respect to the origin of the S.
      cerevisiae COX1 gene in particular and with respect to the origin of introns in
      general.

PMID- 9021129
TI  - Cloning the Yarrowia lipolytica homologue of the Saccharomyces cerevisiae SEC62
      gene.
AB  - Yarrowia lipolytica SEC62 cDNA was cloned by functional complementation of a
      thermo-sensitive sec62 Saccharomyces cerevisiae mutant strain. The Y. lipolytica
      SEC62 promoter region was amplified by the inverse polymerase chain reaction
      (PCR). The cDNA codes for a 396 amino-acid protein with two potential trans
      membrane domains. Y. lipolytica Sec62p behaves as an integral membrane protein as
      shown by Western blotting. Y. lipolytica SEC62 cDNA is able to complement a S.
      cerevisiae sec62 null mutant strain confirming functional conservation, although
      only 53.6% amino-acid similarity is observed between Y. lipolytica and S.
      cerevisiae Sec62.

PMID- 9021130
TI  - Isolation and characterisation of a gene encoding protein disulphide isomerase,
      pdiA, from Aspergillus niger.
AB  - Current strategies to improve the secretion of heterologous proteins from
      Aspergillus niger include the manipulation of chaperones and foldases specific to
      the endoplasmic reticulum (ER). Here we report the isolation of a gene, pdiA,
      encoding a putative protein disulphide isomerase (PDI) from A. niger using the
      Saccharomyces cerevisiae PDI gene as a probe. Sequencing of a genomic clone and
      RT-PCR products predict a 515-aa protein comprising a 20-aa ER-translocation
      signal sequence and a 495-aa mature protein (Mr = 54.3 kDa). The predicted
      protein also contains two thiol oxidoreductase active sites with a -CGHC- motif
      and a carboxy terminal -HDEL ER-retention signal. Three introns were identified
      within the pdiA gene and Southern- and dot-blot analysis indicates that the gene
      is present in a single copy. Northern-blot analysis shows a transcript of the
      predicted size. Sequence homology to a motif associated with protein trafficking
      and the induction of chaperones has been identified in the pdiA promoter.
      Transcription of pdiA is induced 3-4-fold after treatment with tunicamycin, an
      inhibitor of N-linked glycosylation. The kinetics of induction suggest that pdiA
      expression is not part of the primary stress response.

PMID- 9021131
TI  - Cloning and characterization of a Neurospora crassa ribosomal protein gene, crps
      7.
AB  - A Neurospora crassa ribosomal protein gene, crps-7, was isolated from a genomic
      DNA library closely linked to the morphological gene ro-2. Sequence analysis and
      a computerized database search revealed a high degree of homology to the Xenopus
      laevis rps8 and rat rps7 gene, as well as to uncharacterized ORFs from two yeast
      species. Comparison with a nearly full-length cDNA clone revealed two introns,
      one of which is in a conserved position shared with the Xenopus gene. Although a
      number of sequence motifs common to other N. crassa ribosomal protein genes are
      present upstream of the crps-7 gene, mRNA abundance is not tightly regulated by
      carbon availability. Relative transcript levels during nitrogen limitation and
      thermal stress were also examined.

PMID- 9021133
TI  - Transient expression of the beta-glucuronidase gene after biolistic
      transformation of the anaerobic fungus Neocallimastix frontalis.
AB  - The rumen anaerobic fungus Neocallimastix frontalis was biolistically transformed
      using plasmids containing the bacterial beta-glucuronidase gene (GUS) fused to
      the promoter sequences of the enolase gene from N. frontalis. Multiple copies of
      the plasmids were precipitated onto tungsten particles and delivered into
      zoosporangia and a mycelial mat by a helium-driven biolistic device.
      Transformants were detected by histochemical assay for beta-glucuronidase. It was
      found that the enolase promoter sequences tested were responsible for the
      transient expression of the beta-glucuronidase gene. This is the first study
      presenting results on the transformation of an anaerobic fungus.

PMID- 9021132
TI  - Isolation and characterization of rad51 orthologs from Coprinus cinereus and
      Lycopersicon esculentum, and phylogenetic analysis of eukaryotic recA homologs.
AB  - In eubacteria, the recA gene has long been recognized as essential for homologous
      recombination and DNA repair. Recent work has identified recA homologs in
      archaebacteria and eukaryotes, thus emphasizing the universal role this gene
      plays in DNA metabolism. We have isolated and characterized two new recA
      homologs, one from the basidiomycete Coprinus cinereus and the other from the
      angiosperm Lycopersicon esculentum. Like the RAD51 gene of Saccharomyces
      cerevisiae, the Coprinus gene is highly induced by gamma irradiation and during
      meiosis. Phylogenetic analyses of eukarotic recA homologs reveal a gene
      duplication early in eukaryotic evolution which gave rise to two putatively
      monophyletic groups of recA-like genes. One group of 11 characterized genes,
      designated the rad51 group, is orthologous to the Saccharomyces RAD51 gene and
      also contains the Coprinus and Lycopersicon genes. The other group of seven
      genes, designated the dmc1 group, is orthologous to the Saccharomyces DMC1 gene.
      Sequence comparisons and phylogenetic analysis reveal extensive lineage- and gene
      specific differences in rates of RecA protein evolution. Dmc1 consistently
      evolves faster than Rad51, and fungal proteins of both types, especially those of
      Saccharomyces, change rapidly, particularly in comparison to the slowly evolving
      vertebrate proteins. The Drosophila Rad51 protein has undergone remarkably rapid
      sequence divergence.

PMID- 9021134
TI  - Intramolecular cross-overs generate deleted mitochondrial DNA molecules in
      Podospora anserina.
AB  - The unavoidable senescence process that limits the vegetative growth of Podospora
      anserina is always associated with an accumulation of various classes of
      circular, tandemly arranged, defective mitochondrial DNA molecules (senDNAs). The
      monomers of the senDNAs belonging to the so-called beta class share a common
      core, but differ in both their length and termini. To understand the mechanism
      leading to their formation, we have determined the junction sequence of 36 senDNA
      beta monomers present in various senescent cultures. In most cases, we observe
      that: (1) short direct repeats precisely bound the senDNA beta termini and (2)
      one copy of the repeats is retained in the senDNA sequence. Moreover, PCR
      analysis of the mitochondrial DNA of some of the senescent cultures, has allowed
      us to detect another genome which is exactly lacking the sequence of the senDNA
      beta found in the culture. These results demonstrate that an intramolecular
      unequal cross-over occurring between short direct repeats can generate deleted
      mtDNA molecules in P. anserina. In addition, the polymorphism displayed by one
      pair of repeats allows us to establish that this cross-over may be associated
      with a short conversion tract spanning a few (about 15) nucleotides.

PMID- 9021135
TI  - Contribution of various classes of defective mitochondrial DNA molecules to
      senescence in Podospora anserina.
AB  - The unavoidable arrest of vegetative growth in Podospora anserina (senescence
      process) is always correlated with rearrangements of the mitochondrial
      chromosome, mainly consisting in the amplification of particular regions as
      tandemly repeated circular molecules (senDNAs). One sequence systematically
      amplified in senescent cultures corresponds precisely to the first intron (intron
      alpha) of the cox1 gene; nevertheless, other regions (called beta and gamma) are
      also frequently amplified. The experiments presented in this paper show that
      cellular death is in some cases associated with the sole presence of large
      amounts of senDNA beta. In addition, we provide evidence that senDNA beta and
      senDNA alpha accumulate by different mechanisms, as previously proposed. This
      suggests that beta senDNAs have a lethal effect on the mycelium on their own and
      most likely have replicative properties independent of the presence of sequence
      alpha. These data do not fit well with the current opinion that gives an
      essential role to intron alpha in the senescence of P. anserina.

PMID- 9021136
TI  - Short inverted repeats function as hotspots of intermolecular recombination
      giving rise to oligomers of deleted plastid DNAs (ptDNAs).
AB  - We have determined the nucleotide sequences around the junction points of
      oligomeric-deleted ptDNAs possessing a head-to-head or tail-to-tail configuration
      from long-term cultured cell lines and albino plants. It was shown that DNA
      rearrangement occurred by direct fusion of deleted ptDNAs in an inverted
      orientation, which was linked by an asymmetrical sequence of 254-698 bp derived
      from either of the ptDNAs joined. It is notable that inverted repeats of 7-14 bp
      flank the asymmetrical sequences at each of the junction points. These features
      of the DNA sequence around the junction points are commonly observed in
      oligomeric ptDNA with a large-scale deletion regardless of the cell lines
      employed. It is suggested that the short inverted repeats are involved in the
      intermolecular recombination of ptDNA.

PMID- 9021137
TI  - Reduced requirement for RNA editing in the mitochondrial cox3 transcript of Olea
      europaea L.
AB  - Transcripts from the mitochondrial cox3 locus in Olea europaea L. are edited in
      ten nucleotide positions. Nine of these C-to-U transitions affect 3.4% of the
      genomically encoded amino-acid identity to specify a COXIII polypeptide better
      conserved in evolution. RNA editing of cox3 in olive tree mitochondria is, thus,
      less extensive than in the other higher plants so far investigated. This low RNA
      editing frequency might correlate with both the GC content observed in the cox3
      gene and the phylogenetic position of Olea.

PMID- 9021138
TI  - ORF7 of yeast plasmid pGKL2: analysis of gene expression in vivo.
AB  - ORF7 of Kluyveromyces lactis killer plasmid pGKL2 (k2) is capable of encoding a
      putative RNA polymerase subunit of 16 kDa. RNA analysis detected a single,
      plasmid-dependent ORF7 transcript of 550 nt indicating that the gene is
      transcribed mono-cistronically. Attempted one-step gene disruption of ORF7
      resulted in chromosomal integration of the marker gene rather than the formation
      of stable recombinant k2ORF7(0) deletion plasmids. Thus, ORF7 appears to be a
      potential cis-dominant locus the integrity of which is indispensable for plasmid
      stability. The ORF7 gene product was over-produced as a c-myc-tagged fusion
      protein in Escherichia coli. Western-blot analysis of total yeast protein
      extracts using an antibody against this Orf7-c-myc fusion product identified a
      protein band with an apparent molecular weight of 17 kDa. This protein
      corresponds in size to the predicted product and is only detectable in plasmid
      carrying killer yeasts.

PMID- 9021139
TI  - A high-resolution genetic map around waltzer on mouse chromosome 10 and
      identification of a new allele of waltzer.
AB  - A new autosomal recessive mouse mutation characterized by deafness and circling
      behavior was recovered during mutagenesis experiments with chlorambucil (CHL). On
      the basis of allelism tests and linkage analyses, this mutation appears to
      represent a new allele of waltzer (v) that maps to mouse Chromosome (Chr) 10. We
      have designated this new allele, Albany waltzer (vAlb). A high-resolution map of
      the region around v was constructed from data from two intersubspecific
      backcrosses involving Mus musculus castaneus. The analysis of 648 backcross mice
      has allowed vAlb to be localized 1.1 +/- 0.4 cM distal to D10Mit60 and 0.2 +/-
      0.2 cM proximal to a cluster of four markers, D10Mit172, D10Mit112, D10Mit48, and
      D10Mit196. An independent backcross was used to confirm the map order and
      distances in the vAlb backcross. The two linkage maps were consistent, indicating
      that the lesion in vAlb, which is presumed to be a deletion based on the known
      action of CHL, is small and has not significantly altered the map at this level
      of detection. Additionally, three genes (Ros1, Grik2, and Zfa) were eliminated as
      possible candidates for vAlb, and several SSLP markers were separated
      genetically.

PMID- 9021140
TI  - Characterization of the mouse neutrophil elastase gene and localization to
      chromosome 10.
AB  - Neutrophil elastase (NE), a serine proteinase, is considered to play a role in
      normal tissue turnover and host defense, NE may also cause tissue damage in acute
      and chronic inflammatory diseases. We have isolated and characterized the gene
      for mouse NE and determined its chromosomal location. The mouse NE gene has been
      localized by interspecific backcross analysis to Chromosome (Chr) 10. The gene
      for mouse NE is composed of 5 exons and 4 introns, similar to the human NE. Mouse
      NE shares the highly conserved exon size and intron-exon borders with human NE.
      The coding exons of the mouse NE gene predict a translation product in a pre-pro
      form, similar to human NE. Knowledge of the genomic organization and chromosomal
      location of mouse NE may allow us to further define mechanisms responsible for
      cell and tissue-specific expression of mouse NE.

PMID- 9021141
TI  - Structure and expression of the mouse casein gene locus.
AB  - The analysis of yeast artificial chromosomes (YACs) containing the complete mouse
      casein gene locus revealed the presence of five casein genes, alpha-, beta-,
      gamma-, delta-, and kappa-casein, in this order, in the locus. The alpha- and
      beta-casein genes are only 10 kb apart and have convergent transcriptional
      orientations. The distance between the beta-casein gene and the alpha s2-like
      gamma-casein gene is about 70 kb, and these genes have divergent transcriptional
      orientations. The gamma- and delta-casein genes, both encoding a alpha s2-like
      casein, are linked within 60 kb and convergently transcribed. The kappa-casein
      gene is located about 100 kb from the delta-gene. Except for the presence of the
      delta-casein gene, the organization of the mouse casein locus resembles that of
      the bovine locus, including the transcriptional orientation of the genes. In
      contrast to the other casein genes, which are strongly induced at mid-lactation,
      expression of the delta-casein gene is abruptly induced upon parturition.
      Comparative analysis of alpha s2-like sequences from various species suggests
      that the ancestral alpha s2-like gene duplicated around the time of radiation of
      the rodent and artiodactylid ancestors.

PMID- 9021142
TI  - An integrated genetic and physical map of the bovine X chromosome.
AB  - Genotypic data for 56 microsatellites (ms) generated from maternal full sib
      families nested within paternal half sib pedigrees were used to construct a
      linkage map of the bovine X Chromosome (Chr) (BTX) that spans 150 cM (ave.
      interval 2.7 cM). The linkage map contains 36 previously unlinked ms; seven
      generated from a BTXp library. Genotypic data from these 36 ms was merged into an
      existing linkage map to more than double the number of informative BTX markers. A
      male specific linkage map of the pseudoautosomal region was also constructed from
      five ms at the distal end of BTXq. Four informative probes physically assigned by
      fluorescence in situ hybridization defined the extent of coverage, confirmed the
      position of the pseudoautosomal region on the q-arm, and identified a 4.1-cM
      marker interval containing the centromere of BTX.

PMID- 9021143
TI  - A medium-density genetic linkage map of the bovine genome.
AB  - A cattle genetic linkage map was constructed which covers more than 95 percent of
      the bovine genome at medium density. Seven hundred and forty six DNA
      polymorphisms were genotyped in cattle families which comprise 347 individuals in
      full sibling pedigrees. Seven hundred and three of the loci are linked to at
      least one other locus. All linkage groups are assigned to chromosomes, and all
      are orientated with regards to the centromere. There is little overall difference
      in the lengths of the bull and cow linkage maps although there are individual
      differences between maps of chromosomes. One hundred and sixty polymorphisms are
      in or near genes, and the resultant genome-wide comparative analyses indicate
      that while there is greater conservation of synteny between cattle and humans
      compared with mice, the conservation of gene order between cattle and humans is
      much less than would be expected from the conservation of synteny. This map
      provides a basis for high-resolution mapping of the bovine genome with physical
      resources such as Yeast and Bacterial Artificial Chromosomes as well as providing
      the underpinning for the interpolation of information from the Human Genome
      Project.

PMID- 9021145
TI  - Mapping of a haploid transcribed and translated sperm-specific gene to the mouse
      X chromosome.

PMID- 9021144
TI  - Cosmid-derived markers anchoring the bovine genetic map to the physical map.
AB  - The mapping strategy for the bovine genome described in this paper uses large
      insert clones as a tool for physical mapping and as a source of highly
      polymorphic microsatellites for genetic typing, and was one objective of the
      BovMap Project funded by the European Union (UE). Eight-three cosmid and phage
      clones were characterized and used to physically anchor the linkage groups
      defining all the bovine autosomes and the X Chromosome (Chr). By combining
      physical and genetic mapping, clones described in this paper have led to the
      identification of the linkage groups corresponding to Chr 9, 12, 16, and 25. In
      addition, anchored loci from this study were used to orient the linkage groups
      corresponding to Chr 3, 7, 8, 9, 13, 16, 18, 19, and 28 as identified in
      previously published maps. Comparison of the estimated size of the physical and
      linkage maps suggests that the genetic length of the bovine genome may be around
      4000 cM.

PMID- 9021147
TI  - The identification of novel sequences expressed in the mouse notochord.

PMID- 9021146
TI  - A physical map of the mouse H2 Bat5/Db interval.

PMID- 9021148
TI  - Localization of Zap70, the gene for a T cell-specific protein tyrosine kinase, to
      mouse and rat chromosomes by fluorescence in situ hybridization and molecular
      genetic linkage analyses.

PMID- 9021149
TI  - Mapping of the ribonucleotide reductase genes (Rrm1, Rrm2) in the rat.

PMID- 9021150
TI  - Construction and characterization of a large insert porcine YAC library.

PMID- 9021151
TI  - Polymorphic CA-microsatellites for the integration of the bovine genetic and
      physical map.

PMID- 9021152
TI  - Localization of the cell death genes CPP32 and Mch-2 to human chromosome 4q.

PMID- 9021153
TI  - Cloning of the human NADH: ubiquinone oxidoreductase subunit B13: localization to
      chromosome 7q32 and identification of a pseudogene on 11p15.

PMID- 9021155
TI  - Sequence variation and chromosomal mapping of the murine Cdkn2a tumor suppressor
      gene.

PMID- 9021154
TI  - Isolation of the Pax9 cDNA from adult human esophagus.

PMID- 9021156
TI  - The effect of selective genotyping on QTL mapping accuracy.

PMID- 9021157
TI  - Gata2 maps to mouse chromosome 6.

PMID- 9021158
TI  - Genetic mapping of protein kinase C theta (Pkcq) to mouse chromosome 2.

PMID- 9021159
TI  - Linkage mapping of Emx2 to mouse chromosome 19.

PMID- 9021160
TI  - Mapping of the Simpson-Golabi-Behmel overgrowth syndrome gene (GPC3) to
      chromosome X in human and rat by fluorescence in situ hybridization.

PMID- 9021161
TI  - Localization of the beta-nerve growth factor gene (NGFB) to bovine chromosome 3.

PMID- 9021162
TI  - Genetic mapping of thyroglobulin on bovine chromosome 14.

PMID- 9021163
TI  - Genetic mapping of COL3A1 to bovine chromosome 2.

PMID- 9021164
TI  - Mapping the bovine factor H gene to chromosome 16 by SSCP analysis.

PMID- 9021165
TI  - Kininogen (KNG) is linked to loci on cattle chromosome 1 and extends the syntenic
      conservation with human chromosome 3.

PMID- 9021166
TI  - Identification and characterization of a microsatellite marker within murine
      Brca2 gene.

PMID- 9021167
TI  - Formation of reactive oxygen species and DNA strand breakage during interaction
      of chromium (III) and hydrogen peroxide in vitro: evidence for a chromium (III)
      mediated Fenton-like reaction.
AB  - The role of reactive oxygen species in causing DNA damage through interaction of
      chromium (III) and hydrogen peroxide was examined using plasmid relaxation assay
      and EPR spectroscopy. Marked DNA strand breakage was induced by CrCl3 plus H2O2
      in a phosphate buffer at pH 6-8.9; whereas, only slight DNA strand breakage was
      observed during similar treatment at pH less than 4. DNA breakage also increased
      as the reaction temperature and Cr(III)/H2O2 concentrations increased. Control
      experiments with Cr(III) or H2O2 alone did not cause DNA breakage. Sodium azide,
      D-mannitol, Tris-HCl, or catalase completely inhibited Cr(III)/H2O2-induced DNA
      breakage, but superoxide dismutase did not. The D2O enhancing effect on DNA
      breaks was not observed. Cr(III) pre-incubated with a 30-fold molar excess of
      EDTA did not cause any significant DNA breakage in the presence of H2O2. In a
      phosphate buffer containing Cr(III) and H2O2, singlet oxygen and hydroxyl
      radicals were detected using EPR spectrometry with the spin traps 2,2,6,6
      tetramethyl-4-piperidone and 5,5-dimethyl-1-pyrroline 1-oxide (DMPO),
      respectively. DMPO/.OH adducts and DNA breakage induced by Cr(III)/H2O2 were
      markedly higher than those induced by Cr(VI)/H2O2. Furthermore, ascorbate
      decreased Cr(III)/H2O2-induced DNA breakage. EPR studies revealed that ascorbate
      (mole ratio to Cr(III) = 0.5:1) attenuated the DMPO/.OH signal generated by
      Cr(III)/H2O2/DMPO, but a Cr(V) signal and ascorbate radicals were detected.
      NADPH, GSH, and GSSG also decreased DMPO/.OH generated by Cr(III)/H2O2/DMPO;
      however, they were less efficient than ascorbate and no Cr(V) signals were
      detected. This study shows that Cr(III)/H2O2 generates oxidative damage to DNA
      through a Fenton-like reaction: Cr(III) + H2O2-->Cr(IV) + .OH + OH.

PMID- 9021168
TI  - Combined effects of ethanol and cigarette smoke on hepatic and pulmonary
      xenobiotic metabolizing enzymes in rats.
AB  - The combined effects of ethanol (EtOH) and cigarette smoke (CS) on hepatic and
      pulmonary monooxygenase (MO) activities (aniline 4-hydroxylase (AH), aminopyrine
      N-demethylase (AMND), 7-ethoxyresorufin O-deethylase (EROD), p-nitroanisole O
      demethylase (p-NAOD)), lipid peroxidation (LP) and reduced glutathione (GSH)
      levels and glutathione S-transferase (GST) activities toward several substrates
      (l-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB),
      ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP)) were
      determined and compared with those of EtOH or CS alone in rats. When the male
      adult rats (225-275 g) were treated with 10% EtOH (v/v) in their drinking for 21
      days AH, AMND and EROD activities and LP and GSH levels increased significantly
      whereas GST activity for EAA decreased significantly in liver as compared to
      controls. EtOH did not change the hepatic p-NAOD and GST activities toward CDNB,
      DCNB and ENPP. In lung, EtOH increased GST activities toward CDNB and ENPP and LP
      level but decreased GST activity toward DCNB, significantly. No alterations were
      noted in pulmonary MO activities and GST activity toward EAA and GSH level by
      EtOH treatment. When the animals were exposed to CS five times a day, with 1 h
      intervals, for 3 days in a chamber where smoke and fresh air lead alternatively,
      AMND, EROD and p-NAOD activities, GST activity toward EAA and GSH level increased
      but LP level and GST activity for ENPP decreased significantly in liver. CS did
      not alter the hepatic AH and GST activities toward CDNB and DCNB. In lung, CS
      increased AH, EROD and p-NAOD activities and LP and GSH levels and decreased all
      the GST activities studied significantly. CS had no influence on pulmonary AMND
      activity. For the combined treatment, the animals were treated with 10% EtOH
      (v/v) in their drinking water for 21 days and during the last 3 days they were
      exposed to CS five times a day, with 1 h intervals, in a chamber where smoke and
      fresh air lead alternatively. In these animals, augmentation of elevations were
      noted in AH and p-NAOD activities and LP and GSH levels but not in EROD and AMND
      activities in liver. Combined treatment significantly decreased GST activity
      toward CDNB, ameliorated the alteration caused by either EtOH or CS treatment
      alone on GST activity toward EAA and potentiated the depression of GST activity
      toward ENPP to a greater degree. No change was observed in GST activity toward
      DCNB. In lung, combined treatment potentiated the elevations of AMND and p-NAOD
      activities and LP level and not those of AH and EROD activities. GST activities
      toward CDNB, DCNB and ENPP were highly elevated by the combined treatment. No
      changes were observed in pulmonary GSH level and GST activity for EAA by the
      combined treatment. These results reveal that the regulations of the hepatic and
      pulmonary MO and GST are differentially influenced by EtOH, CS and the combined
      treatment.

PMID- 9021169
TI  - The biotransformation of isoprene and the two isoprene monoepoxides by human
      cytochrome P450 enzymes, compared to mouse and rat liver microsomes.
AB  - The metabolism of isoprene was investigated with microsomes derived from cell
      lines expressing human CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, or
      CYP3A4. The formation of epoxide metabolites was determined by gas
      chromatographic analysis. CYP2E1 showed the highest rates of formation of the
      isoprene monoepoxides 3,4-epoxy-3-methyl-1-butene (EPOX-I) and 3,4-epoxy-2-methyl
      1-butene (EPOX-II), followed by CYP2B6. CYP2E1 was the only enzyme showing
      detectable formation of the diepoxide of isoprene, 2-methyl-1,2:3,4
      diepoxybutane. Both isoprene monoepoxides were oxidized by CYP2E1 to the
      diepoxide at similar enzymatic rates. In order to determine the relative role of
      CYP2E1 in hepatic metabolism, isoprene as well as the two monoepoxides were also
      incubated with a series of ten human liver microsomal preparations in the
      presence of the epoxide hydrolase inhibitor cyclohexene oxide. The obtained
      activities were correlated with activities towards specific substrates for
      CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A. The results were supportive for
      those obtained with single human P450 enzymes. Isoprene (monoepoxide) metabolism
      sowed a significant correlation with CYP2E1 activity, determined as chlorzoxazone
      6-hydroxylation. CYP2E1 is therefore the major enzyme involved in hepatic
      metabolism of isoprene and the isoprene monoepoxides in vitro. To investigae
      species differences with regard to the role of epoxide hydrolase in the
      metabolism of isoprene monoepoxides, the epoxidation of isoprene by human liver
      microsomes was compared to that of mouse and rate liver microsomes. The amounts
      of monoepoxides formed as a balance between epoxidation and hydrolysis, was
      measured in incubations with and without the epoxide hydrolase inhibitor
      cyclohexene oxide. Inhibition of epoxide hydrolase resulted in similar rates of
      monoepoxide formation in mouse, rat and man. Without inhibitor, however, the
      total amount of monoepoxides present at the end of the incubation period was
      twice as high for mouse liver microsomes than for rat and even 15 times as high
      as for human liver microsomes. Thus, differences in epoxide hydrolase activity
      between species may be of crucial importance for the toxicity of isoprene in the
      various species.

PMID- 9021170
TI  - Effects of arenastatin A and its synthetic analogs on microtubule assembly.
AB  - Inhibition of microtubule assembly by arenastatin A (1) and five synthetic
      analogs (3-7) was examined. Arenastatin A and the triamide 6 showed potent and
      moderately strong inhibitory activities, respectively (IC50; 2.3 microM for 1,
      7.8 microM for 6) and also depolymerized preformed microtubules. The other
      analogs tested showed no activity.

PMID- 9021172
TI  - Activity of a new triazole, Sch 56592, compared with those of four other
      antifungal agents tested against clinical isolates of Candida spp. and
      Saccharomyces cerevisiae.
AB  - Sch 56592 is a new triazole agent with potent, broad-spectrum antifungal
      activity. The in vitro activities of Sch 56592, itraconazole, fluconazole,
      amphotericin B, and flucytosine (5-FC) against 404 clinical isolates of Candida
      spp. (382 isolates) and Saccharomyces cerevisiae (22 isolates) were investigated.
      In vitro susceptibility testing was performed by a broth microdilution method
      performed according to National Committee for Clinical Laboratory Standards
      guidelines. Overall, Sch 56592 was very active (MIC at which 90% of isolates are
      inhibited [MIC90], 0.5 microgram/ml) against these yeast isolates. Sch 56592 was
      most active against Candida tropicalis, Candida parapsilosis, candida lusitaniae,
      and Candida stellatoidea (MIC90, < or = 0.12 microgram/ml) and was least active
      against Candida glabrata (MIC90, 2.0 micrograms/ml). Sch 56592 was 2- to 32-fold
      more active than amphotericin B and 5-FC against all species except C. glabrata.
      By comparison with the other triazoles, Sch 56592 was equivalent to itraconazole
      and greater than or equal to eightfold more active than fluconazole. On the basis
      of these results, Sch 56592 has promising antifungal activity, and further in
      vitro and in vivo investigations are warranted.

PMID- 9021171
TI  - Carbapenem-hydrolyzing beta-lactamases.

PMID- 9021173
TI  - Survival of anti-Clostridium difficile bovine immunoglobulin concentrate in the
      human gastrointestinal tract.
AB  - To be therapeutically active, oral hyperimmune bovine immunoglobulin concentrate
      (BIC) must survive its passage through the intestinal tract. This led us to study
      the gastrointestinal stability of orally administered BIC directed against
      Clostridium difficile toxins (BIC-C. difficile). BIC-C. difficile was stable at
      neutral pH in vitro but was degraded at low pH, particularly in the presence of
      pepsin. Healthy volunteers (n = 6) took BIC-C. difficile (45 or 8 g) as a single
      oral dose. Total bovine immunoglobulin G (IgG) and specific anti-C. difficile IgG
      were measured in the stool. BIC was given under the following conditions: in the
      fasting state, in the fed state, with antacid, during omeprazole therapy, or in
      enteric capsules (released at pH > 6). The mean fecal bovine IgG content of 3-day
      stool collections was similar in the fasting (536 mg; 3.8% of the ingested dose
      of BIC), fed (221 mg; 1.6%), and antacid (381 mg; 2.7%) groups. Omeprazole
      therapy was associated with increased fecal bovine IgG levels (1253 mg; 8.8%),
      but this difference did not reach statistical significance (P = 0.07).
      Administration of 8 g of BIC-C. difficile in enteric capsules resulted in
      substantially higher fecal bovine IgG levels (1,124 mg; 32.7% of the oral dose)
      than those obtained after administration of nonencapsulated BIC (22 MG; 0.6%; P =
      0.004). An inverse relationship was noted between intestinal transit time and
      fecal bovine IgG content (R = 0.83; P = 0.04 [data from omeprazole group]).
      Filtrates of stool samples collected after oral administration of BIC-C.
      difficile neutralized the cytotoxicity of C. difficile toxins A and B, whereas
      control stool filtrates did not. Bovine colostral IgG undergoes partial
      degradation in the intestinal tract. Exposure to acidic gastric secretions and
      prolonged colonic transit may both contribute to IgG degradation. Nonetheless,
      humans taking BIC-C. difficile orally have neutralizing antitoxin activity in
      their stool.

PMID- 9021174
TI  - Clinically used antimicrobial drugs against experimental pneumocystosis, singly
      and in combination: analysis of drug interactions and efficacies.
AB  - We analyzed single drugs and combinations of drugs used clinically in the
      treatment of opportunistic infections and other conditions for their activities
      against Pneumocystis carinii pneumonia in immunosuppressed rats. When they were
      used alone, atovaquone, rifabutin, and dapsone were more active than
      clarithromycin or trimethoprim. Drug combinations were evaluated for synergistic
      activity by an analysis of variance model for two-way factorial experiments and a
      response surface model. Atovaquone combined with trimethoprim trimethoprim and
      some combinations of dapsone and clarithromycin was synergistic; however, the
      activities of combinations of atovaquone and rifabutin, atovaquone and
      clarithromycin, and atovaquone and dapsone were simply additive. Lovastatin,
      which inhibits 3-hydroxy-methylglutaryl coenzyme A reductase, was inactive
      whether it was used alone or in combination with other agents. None of the
      synergistic drug combinations was as effective as trimethoprim-sulfamethoxazole.
      We conclude that the rat model can be used to test combinations of anti-P.
      carinii agents for synergistic activity by well-established statistical
      techniques. While some combinations of clinically used antimicrobial drugs have
      enhanced anti-P. carinii activity, further studies are needed before clinical
      trials can be contemplated.

PMID- 9021175
TI  - Immunodeficient and immunosuppressed mice as models to test anti-Pneumocystis
      carinii drugs.
AB  - Congenitally immunodeficient and immunosuppressed normal mice with naturally
      acquired Pneumocystis carinii infection were compared as models for testing anti
      P. carinii drugs. Among the immunodeficient mice, mice with severe combined
      immunodeficiency disease (scid), which lack B and T cells, had higher levels of
      P. carinii pneumonia than did microMT mice, which lack K cells. Normal mice
      administered dexamethasone in the drinking water had more extensive
      pneumocystosis than mice administered parenteral methylprednisolone or hybridoma
      cells making a monoclonal antibody to CD4 cells. The standard anti-P. carinii
      drugs trimethoprim (TMP)-sulfamethoxazole (SMX), pentamidine, and atovaquone,
      which work well in rats and humans, worked well in the mice. Clindamycin and
      primaquine were effective in the scid and microMT mice but not in the
      immunosuppressed normal mice. High doses of epiroprim, an analog of TMP, appeared
      to enhance the activities of low doses of SMX and dapsone, while high doses of
      TMP did not; however, further studies are needed before definitive conclusions
      about the actions of these drugs can be drawn. Taken together, the data obtained
      in this study support the growing body of literature suggesting that the mouse is
      a valid alternative to the rat as a model for testing anti-P. carinii drugs.
      Additional differences involving the activities of individual drugs in these
      models will probably emerge as more experience is gained.

PMID- 9021176
TI  - Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of
      pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis remains an important cause of morbidity and
      mortality among transplant recipients and patients receiving cancer chemotherapy.
      The lipid-associated formulation of amphotericin B (AmB), AmB lipid complex
      (ABLC), was evaluated for its prophylactic efficacy when it was administered as
      an aerosol in a rat model of pulmonary aspergillosis. Aerosol ABLC (aero-ABLC),
      in doses from 0.4 to 1.6 mg/kg of body weight given 2 days before infection,
      significantly delayed mortality compared to the mortality of rats given placebo
      (P < 0.001). At day 10 postinfection, 50% of rats in the 0.4-mg/kg group and 75%
      of rats in the 1.6-mg/kg group were alive, while all control animals had died. In
      a second trial aero-ABLC was more effective than an equivalent dose of aerosol
      AmB (aero-AmB) in prolonging survival, with 100% survival at day 14 postinfection
      in the ABLC group, compared to 62.5% survival in the AmB group. Mean
      concentrations of AmB in lungs were 3.7 times higher at day 1 (P < 0.002) and
      almost six times higher at day 7 (P < 0.001) after treatment with aero-ABLC than
      after treatment with a similar dose of aero-AmB. We conclude that aero-ABLC
      provided higher and more prolonged levels of the parent compound in the lungs
      than aero-AmB and was more effective in delaying mortality from aspergillosis in
      this model.

PMID- 9021178
TI  - Characterization of Mycoplasma hominis mutations involved in resistance to
      fluoroquinolones.
AB  - Fluoroquinolone-resistant mutants of Mycoplasma hominis were selected in vitro
      from the PG21 susceptible reference strain either by multistep selection on
      increasing concentrations of various fluoroquinolones or by one-step selection on
      agar medium with ofloxacin. The quinolone resistance-determining regions (QRDR)
      of the structural genes encoding the A and b subunits of DNA gyrase were
      amplified by PCR, and the nucleotide sequences of eight multistep-selected
      resistant strains were compared to those of susceptible strain PG21. Four high
      level resistant mutants that were selected on norfloxacin or ofloxacin contained
      a C-to-T transition in the gyrA QRDR, leading to substitution of Ser-83 by Leu in
      the GyrA protein. Analysis of the sequence of the gyrB QRDR of the eight
      multistep-selected mutants did not reveal any difference compared to that of the
      gyrB QRDR of the reference strain M. hominis PG21. Similar analyses of eight one
      step-selected mutants did not reveal any base change in the gyrA and gyrB QRDRs.
      These results suggest that in M. hominis, like in other bacterial species, a gyrA
      mutation at Ser-83 is associated with fluoroquinolone resistance.

PMID- 9021179
TI  - Uptake and intracellular activity of trovafloxacin in human phagocytes and tissue
      cultured epithelial cells.
AB  - The penetration of trovafloxacin into human polymorphonuclear leukocytes (PMNs),
      human peritoneal macrophages, and tissue-cultured epithelial cells (McCoy cells)
      was evaluated. The cellular concentration to extracellular concentration (C/E)
      ratios of trovafloxacin were greater than 9 for extracellular concentrations
      ranging from 0.5 to 25 micrograms/ml. The uptake of trovafloxacin by PMNs was
      rapid, reversible, nonsaturable, not energy dependent, and significantly
      increased at 4 degrees C. Ingestion of opsonized zymosan, but not opsonized
      Staphylococcus aureus, significantly increased the amount of PMN-associated
      trovafloxacin. This agent at concentrations of 0.5 and 1 microgram/ml induced a
      greater reduction in the survival of intracellular S. aureus in PMNs than
      ciprofloxacin and ofloxacin. It was concluded that trovafloxacin reaches
      concentrations within phagocytic and nonphagocytic cells several times higher
      than the extracellular ones, while it remains active in PMNs.

PMID- 9021177
TI  - SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the
      replicative cycle of human immunodeficiency virus.
AB  - From a series of macrocyclic diamides possessing the disulfide linkage, only SRR
      SB3, a compound that complexes with zinc, was found to inhibit human
      immunodeficiency virus type 1 (HIV-1; strain IIIB) replication at a concentration
      of 1.8 to 6.5 micrograms/ml in MT-4, CEM, and peripheral blood mononuclear cells.
      SRR-SB3 was toxic to MT-4 cells at a concentration of 15.9 micrograms/ml,
      resulting in a selectivity index of 9 in these cells. This macrolide was also
      effective against various other HIV-1 strains, including clinical isolates and
      HIV-1 strains resistant to protease inhibitors and nucleoside and nonnucleoside
      reverse transcriptase inhibitors. It was also active against various HIV-2
      strains, simian immunodeficiency virus (strain MAC251), and Moloney murine
      sarcoma virus, but not against viruses other than retroviruses. In addition, the
      compound was found to inhibit chronic HIV-1 infections in vitro. The compound in
      combination with other antiviral agents, such as zidovudine, zalcitabine, and
      stavudine, showed an effect that was between additive and synergistic. Time-of
      addition experiments indicated that SRR-SB3 acts at a late stage of the HIV-1
      replicative cycle.

PMID- 9021180
TI  - A zidovudine-resistant simian immunodeficiency virus mutant with a Q151M mutation
      in reverse transcriptase causes AIDS in newborn macaques.
AB  - The simian immunodeficiency virus (SIV)-newborn rhesus macaque model of AIDS can
      be used to study directly the virulence of viral mutants which are resistant to
      antiviral drugs. A viral mutant called SIVmac79A6.1, isolated from an SIV
      infected macaque after prolonged zidovudine treatment, was found to have a double
      base-pair change at codon 151 of reverse transcriptase, resulting in a glutamine
      to methionine substitution (Q151M). This mutation was associated with more than
      100-fold increased resistance to zidovudine and low-level cross-resistance to
      other dideoxynucleoside analogs. To determine whether this Q151M mutation affects
      viral virulence, four newborn macaques were inoculated intravenously with a
      biological clone of this drug-resistant SIVmac79A6.1 mutant; two of these animals
      were also treated orally with zidovudine. All four animals showed persistent
      viremia, and two of the four animals developed fatal immunodeficiency at 3 and 8
      months of age, respectively. The remaining two animals had CD4+ T-cell depletion
      and clinical symptoms of AIDS at 22 months. No phenotypic or genotypic reversion
      of virus to the wild type could be detected in any of the four animals. These
      results demonstrate that the Q151M mutation in SIV reverse transcriptase does not
      reduce viral virulence.

PMID- 9021182
TI  - Antibiotic resistance among clinical isolates of Haemophilus influenzae in the
      United States in 1994 and 1995 and detection of beta-lactamase-positive strains
      resistant to amoxicillin-clavulanate: results of a national multicenter
      surveillance study.
AB  - A total of 1,537 clinical isolates of Haemophilus influenzae were recovered in 30
      U.S. medical center laboratories between 1 November 1994 and 30 April 1995 and
      were characterized in a central laboratory with respect to serotype and beta
      lactamase production and the in vitro activities of 15 oral antimicrobial agents.
      Overall, 36.4% of the isolates were found to produce beta-lactamase. The rank
      order of activity of six cephalosporins on the basis of MICs was cefixime >
      cefpodoxime > cefuroxime > loracarbef > or = cefaclor > cefprozil. On the basis
      of current National Committee for Clinical Laboratory Standards (NCCLS)
      breakpoints ages of isolates found to be resistant or intermediate to these
      agents were as follows: 0.1, 0.3, 6.4, 16.3, 18.3, and 29.8, respectively
      (National Committee for Clinical Laboratory Standards. Methods for dilution
      antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. M7
      A4, 1995). Azithromycin was, on a weight basis, the most potent of the macrolides
      tested in this study, followed by erythromycin and then clarithromycin.
      Azithromycin was typically fourfold more active than erythromycin, which was, in
      turn, slightly more active than clarithromycin. However, when compared on the
      basis of the frequency of resistance determined by using current NCCLS
      breakpoints, there was essentially no difference between azithromycin and
      clarithromycin, i.e., 0.5 and 1.9%, respectively (P = 0.086). Interpretive
      breakpoints for erythromycin MIC tests versus H. influenzae have not been
      developed. Resistance to other non- beta-lactam agents was variable, as follows:
      trimethoprim-sulfamethoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%;
      and rifampin, 0.3%. Two conspicuous findings in this study were the
      identification of 39 strains H. influenzae that were beta-lactamase negative but
      ampicillin intermediate or resistant (BLNAR) and, even more surprisingly, 17 beta
      lactamase-positive isolates that were resistant to amoxicillin-clavulanate
      (BLPACR). Strains of H. influenzae in the first group have heretofore been very
      uncommon; organisms in the second group have not previously been described in the
      literature. The percentages of all study isolates comprised of BLNAR and BLPACR
      organisms were 2.5 and 1.1, respectively. Overall resistance to ampicillin was
      thus 38.9%, and that to amoxicillin-clavulanate was 4.5%.

PMID- 9021181
TI  - Line probe assay for rapid detection of drug-selected mutations in the human
      immunodeficiency virus type 1 reverse transcriptase gene.
AB  - Upon prolonged treatment with various antiretroviral nucleoside analogs such as
      3'-azido-3'-deoxythymidine, 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, (-)-
      beta-L-2', 3'dideoxy-3'thiacytidine and 2',3'-didehydro-3'-deoxythymidine,
      selection of human immunodeficiency virus type 1 (HIV-1) strains with mutations
      in the reverse transcriptase (RT) gene has been reported. We designed a reverse
      hybridization line probe assay (LiPA) for the rapid and simultaneous
      characterization of the following variations in the RT gene: M41 or L41; T69,
      N69, A69, or D69; K70 or R70; L74 or V74; V75 or T75; M184, I184, or V184; T215,
      Y215, or F215; and K219, Q219, or E219. Nucleotide polymorphisms for codon L41
      (TTG or CTG), T69 (ACT or ACA), V75 (GTA or GTG), T215 (ACC or ACT), and Y215
      (TAC or TAT) could be detected. In addition to the codons mentioned above,
      several third-letter polymorphisms in the direct vicinity of the target codons
      (E40, E42, K43, K73, D76, Q182, Y183, D185, G213, F214, and L214) were found, and
      specific probes were selected. In total, 48 probes were designed and applied to
      the LiPA test strips and optimized with a well-characterized and representative
      reference panel. Plasma samples from 358 HIV-infected patients were analyzed with
      all 48 probes. The amino acid profiles could be deduced by LiPA hybridization in
      an average of 92.7% of the samples for each individual codon. When combined with
      changes in viral load and CD4+ T-cell count, this LiPA approach proved to be
      useful in studying genetic resistance in follow-up samples from antiretroviral
      agent-treated HIV-1-infected individuals.

PMID- 9021183
TI  - In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal
      carbapenem.
AB  - ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial
      spectrum and a potent antipseudomonal activity. It showed high in vitro activity,
      comparable to those of meropenem and a new carbapenem, BO-2727, against
      methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at
      which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml.
      Against methicillin-resistant S. aureus, ER-35786 was the most active among the
      compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the
      family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER
      35786 inhibited 90% of strains tested at a concentration of < or = 1.56
      micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13
      micrograms/ml, and the compound was more active than meropenem. In addition, the
      activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime
      resistant P. aeruginosa was equal to or higher than that of the most active
      reference compound. The in vivo activity of ER-35786 was consistent with this in
      vitro activity. The in vivo activity of ER-35786 was highest for systemic
      infection models with methicillin-resistant S. aureus and beta-lactam-resistant
      P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786
      produced a greater reduction in the viable cell count in the lungs than did
      imipenem-cilastatin or meropenem.

PMID- 9021184
TI  - Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas
      aeruginosa in mice.
AB  - We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of
      fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine
      gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was
      induced by administering cyclophosphamide (CY) and ampicillin to specific
      pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of
      body weight per day twice a day after the second CY administration significantly
      increased the survival rate compared to that for control mice treated with
      saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased
      the survival rate (from 30% for control mice to 80% for treated mice). The
      bacterial counts in the liver and blood were both significantly lower in FOM(+)
      treated mice in comparison with those in liver and blood of saline-treated
      control mice. FOM(+) administration affected neither the bacterial colonization
      in the intestinal tract nor the leukocyte counts in the peripheral blood of the
      mice. After intravascular inoculation of P. aeruginosa, treatment of mice with
      FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or
      not enhance bacterial clearance from the blood of mice pretreated or not
      pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha,
      interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut
      derived sepsis. These results indicate that both FOM and FOM(+) have protective
      effects against P. aeruginosa bacteremia, despite a lack of specific activity of
      FOM(+), and suggest that FOM may possess immunomodulating activity and that it
      induces a protective effect. The protective mechanism is speculated to be that
      FOM modulates the vivo production of inflammatory cytokines.

PMID- 9021185
TI  - Characterization of the 6'-N-aminoglycoside acetyltransferase gene aac(6')-Im
      [corrected] associated with a sulI-type integron.
AB  - The amikacin resistance gene aac(6')-Im [corrected] from Citrobacter freundii
      Cf155 encoding an aminoglycoside 6'-N-acetyltransferase was characterized. The
      gene was identified as a coding sequence of 521 bp located down-stream from the
      5' conserved segment of an integron. The sequence of this aac(6')-Im [corrected]
      gene corresponded to a protein of 173 amino acids which possessed 64.2% identity
      in a 165-amino-acid overlap with the aac(6')-Ia gene product (F.C. Tenover, D.
      Filpula, K.L. Phillips, and J. J. Plorde, J. Bacteriol. 170:471-473, 1988). By
      using PCR, the aac(6')-Im [corrected] gene could be detected in 8 of 86 gram
      negative clinical isolates from two Belgian hospitals, including isolates of
      Citrobacter, Klebsiella spp., and Escherichia coli. PCR mapping of the aac(6')-Im
      [corrected] gene environment in these isolates indicated that the gene was
      located within a sulI-type integron; the insert region is 1,700 bases long and
      includes two genes cassettes, the second being ant (3")-Ib.

PMID- 9021186
TI  - Decoy approach using RNA-DNA chimera oligonucleotides to inhibit the regulatory
      function of human immunodeficiency virus type 1 Rev protein.
AB  - Human immunodeficiency virus type 1 (HIV-1) encodes two regulatory proteins, Tat
      and Rev, that bind to target RNA sequences. These are the trans-activation
      responsive (TAR) RNA and the Rev-responsive element (RRE), respectively. The Rev
      protein shifts RNA synthesis to viral transcripts by binding to the RRE within
      the env gene. In the present study we prepared a RNA-DNA chimera consisting of 29
      or 31 nucleotides to inhibit the Rev regulatory function by means of the decoy
      approach. The chimera oligonucleotides (anti-Rev oligonucleotides [AROs])
      contained an RNA "bubble" structure (13 oligonucleotides; the Rev-binding element
      in RRE) that bound Rev with a high affinity in an in vitro assay. The controls
      were RNA-DNA chimera oligonucleotides (negative control oligonucleotides [NCOs])
      similar to ARO, but without the bubble structure, that bound with considerably
      less affinity to Rev. When the inhibitory effects of these decoys on HIV-1
      replication were examined, we found that AROs, but no NCOs, reduced more than 90%
      of the HIV-1 production generated by productively infected human T-cell lines.
      The production of primary HIV-1 isolates in healthy donor-derived peripheral
      blood mononuclear cells was also similarly inhibited by AROs. In addition, the
      induction of viral mRNAs and antigens in latently HIV-1-infected ACH-2 cells by
      tumor necrosis factor alpha was specifically inhibited by AROs, but not by NCOs.
      No apparent cytotoxicity was caused by either decoy. Thus, the use of a Rev
      binding element-based decoy, the RNA-DNA chimera oligonucleotide, may represent a
      safer approach to gene therapy for reducing the virus load in HIV-1-infected
      individuals.

PMID- 9021187
TI  - Experimental evaluation of possible new short-term drug regimens for treatment of
      multibacillary leprosy.
AB  - Groups of nude mice, with both hind footpads infected with 10(8) Mycobacterium
      leprae organisms, were treated with 4-week courses of different drug
      combinations. The effect treatment on each group was evaluated by subinoculating
      footpad homogenates from the treated mice into groups of normal and nude mice for
      subsequent regrowth, assessed 1 year later. A combination of rifampin (RMP) with
      clarithromycin (CLARI), minocycline (MINO), and ofloxacin (OFLO) resulted in the
      complete killing of M. leprae after 3 weeks of treatment. A combination of
      sparfloxacin (SPAR) and RMP also resulted in a similar bactericidal effect after
      3 weeks of treatment. Other drug combinations showed variable effects. Very
      little or no effect was observed with any regimen if the treatment was given for
      less than 2 weeks. World Health Organization (WHO) multidrug therapy (MDT) given
      for 8 weeks was as effective as the two combinations described above. The results
      suggest that multidrug combinations consisting of RMP-OFLO (or SPAR)-CLARI
      (and/or MINO) are as effective as the WHO MDT for the treatment of experimental
      leprosy. Moreover, they imply that these combinations, which were found to be
      active in a 4-week experimental treatment protocol, could be administered as
      treatment to patients for a period of time shorter than the present 2-year
      regimen without a loss of effectiveness.

PMID- 9021188
TI  - Pneumocandin L-743,872 enhances the activities of amphotericin B and fluconazole
      against Cryptococcus neoformans in vitro.
AB  - Cryptococcus neoformans infections in patients with AIDS are often incurable,
      despite aggressive antifungal therapy. Combination regimens with additive or
      synergistic drugs could provide additional options for treating cryptococcal
      meningitis. We evaluated the efficacy of combination therapies using L-743,872, a
      pneumocandin antifungal drug, and amphotericin B or fluconazole against 18
      strains of C. neoformans, including 11 C. neoformans var. neoformans, 3 C.
      neoformans var. gattii, and 4 fluconazole-resistant isolates. The combination of
      subinhibitory concentrations of L-743,872 with amphotericin B significantly
      enhanced amphotericin B activity against C. neoformans as measured by turbidity
      (antifungal susceptibility studies using the National Committee of Clinical and
      Laboratory Standards method), quantitative CFU, and tetrazolium salt reduction
      assays. Similarly, the addition of subinhibitory concentrations of L-743,872 to
      fluconazole enhanced fluconazole activity, but the effect was less dramatic than
      for the pneumocandin-amphotericin B combination. A marked synergism was observed
      in all combinations of amphotericin B and L-743, 872 (fractional inhibitory
      concentration index [FIC] of < or = 0.5). Fluconazole-resistant strains showed a
      susceptibility to amphotericin B and L-743,872 which was comparable to that of
      susceptible isolates. Combinations of pneumocandin with fluconazole revealed
      different activities for the various strains, including synergism (FIC < 1.0),
      additivity (FIC = 1.0), and autonomy (FIC between 1.0 and 2.0). Combination
      studies with fluconazole and L-743,872 showed additive and autonomous activities
      against fluconazole-resistant isolates. No antagonistic interactions (FIC < 2.0)
      were observed for any combination of L-743,872 with either amphotericin B or
      fluconazole. The results of this study suggest that L-743,872 can enhance the
      efficacy of fluconazole or amphotericin B in vitro and indicate a potential role
      for L-743,872 in combination therapy against C. neoformans.

PMID- 9021189
TI  - Use of a fluorescent probe to assess the activities of candidate agents against
      intracellular forms of Encephalitozoon microsporidia.
AB  - Microsporidia are obligate intracellular protozoan parasites. Three species of
      the genus Encephalitozoon are among the microsporidia that infect immunodeficient
      humans. These species, Encephalitozoon cuniculi, Encephalitozoon hellem, and
      Encephalitozoon intestinalis, all develop in a parasitophorous vacuole within a
      host cell. The present study describes a method that uses the fluorescent probe
      calcein and confocal microscopy to detect drug-induced effects in Encephalitozoon
      infected green monkey kidney cells. The effects were as follows: (i) changes in
      parasite organization within the parasitophorous vacuole; (ii) swelling and gross
      morphological changes of parasite developing stages in situ; (iii) killing of
      developing parasite stages in situ, detected by their uptake of the fluorescent
      probe; and (iv) reduction in the viability of the host cell population, assessed
      by the loss of the probe. Verapamil and itraconazole were used to increase the
      vital dye loading by both uninfected and infected cells. Agents with known
      antimicrosporidial activity, albendazole and fumagillin, caused all three types
      of parasite changes at concentrations that had no detectable effect on host cell
      viability. The effective doses of albendazole and fumagillin that caused swelling
      and disorganization of parasite developing stages were 5 x 10(-7) and 10(-6) M
      respectively. Killing of developing stages was detected at 10-fold-higher
      concentrations for these agents and at 10(-5) M for metronidazole. This method
      can be used to screen candidate antimicrosporidial agents in infected cultured
      cells.

PMID- 9021190
TI  - Use of a new mouse model of Acinetobacter baumannii pneumonia to evaluate the
      postantibiotic effect of imipenem.
AB  - Acinetobacter baumannii is responsible for severe nosocomial pneumonia. To
      evaluate new therapeutic regimens for infections due to multiresistant strains
      and to study the pharmacodynamic properties of various antibiotics, we developed
      an experimental mouse model of acute A. baumannii pneumonia. C3H/HeN mice
      rendered transiently neutropenic were infected intratracheally with 5 x 10(6) CFU
      of A. baumannii. The mean log10 CFU/g of lung homogenate (+/- the standard
      deviation) were 9 +/- 0.9, 9.4 +/- 0.8, 8.6 +/- 1.2, and 7.7 +/- 1.4 on days 1,
      2, 3, and 4 postinoculation. The lung pathology was characterized by pneumonitis
      with edema and a patchy distribution of hemorrhages in the peribronchovascular
      spaces of both lungs. Abscesses formed on days 3 and 4. Four days after
      inoculation, subacute pneumonitis characterized by alveolar macrophage
      proliferation and areas of fibrosis was observed. The cumulative mortality on day
      4 was 85%. This new model was used to study the effects of 1, 2, or 3 50-mg/kg
      doses of imipenem. Imipenem concentrations in lungs were above the MIC for 2 h
      after the last dose. The in vivo postantibiotic effect (PAE) was determined
      during the 9-h period following the last dose; it decreased in duration with the
      number of doses: 9.6, 6.4, and 4 h after 1, 2, and 3 50-mg/kg doses,
      respectively. In contrast, no in vitro PAE was observed. This model offers a
      reproducible acute course of A. baumannii pneumonia. The presence of a prolonged
      in vivo PAE supports the currently recommended dosing intervals of imipenem for
      the treatment of human infections due to A. baumannii, i.e., 15 mg/kg three times
      a day.

PMID- 9021191
TI  - Relationships between antimicrobial effect and area under the concentration-time
      curve as a basis for comparison of modes of antibiotic administration: meropenem
      bolus injections versus continuous infusions.
AB  - In comparative studies of different modes of administration (MAs) simulated in in
      vitro dynamic models, only one dose of antibiotic is usually mimicked. Such an
      experimental design can provide a prediction of the antimicrobial effect (AME) of
      a given combination of drug, clinical isolate, and infection site, but may be
      inappropriate for accurate comparison of MAs. An alternative design providing
      comparison of different MAs with various antibiotic doses in a wide range and
      with evaluation of the respective relationships between AME and the AUC was
      proposed and examined. Two series of meropenem pharmacokinetic profiles, i.e.,
      monoexponentially decreasing concentrations (bolus doses) and constant
      concentrations (6-h continuous infusion), were in vitro simulated. The simulated
      initial concentrations (Co[from 0.62 to 48 micrograms/ml]) and steady-state
      concentrations (Css[from 0.016 to 8 micrograms/ml]) were chosen to provide
      similar AUC for 0 to 6 h (AUC0-6) ranges for both MAs (from 0.070 to 50.0
      micrograms.h/ml and from 0.09 to 48.0 micrograms.h/ml, respectively). The AME of
      meropenem on Staphylococcus aureus ATCC 25923 (MIC, 0.06 micrograms/ml) was
      determined at each time (t) point as a difference (E) between the logarithms of
      viable counts (N) in the control cultures without antibiotic (NC) and in cultures
      exposed to antibiotics (NA). Time courses of E observed at different Co of Css
      levels were compared in terms of the areas under the E-t curves (ABBCt). The
      finite values of the ABBCt observed by the end of the 6 -h observation period,
      which are equivalent to the area between bacterial count-time curves observed in
      the absence and presence of antibiotic (ABBC), were plotted versus the respective
      AUCs produced by each of the MAs. The ABBC versus AUC curves had a similar
      pattern: a plateau achieved at high AUCs followed by a steep rise in ABBC at
      relatively low AUCs was inherent in both of the MAs. The superiority of bolus
      dosing over the infusions could be documented only for meropenem concentrations
      below the MIC. At higher Co or Css (i.e., at an AUC of > or = 0.4
      micrograms.h/ml), the ABBC versus AUC curves plotted for each of the MAs could
      practically be superimposed. On the whole, both MAs appeared to be equiefficient
      in terms of the ABBC. These results suggest that AUC analysis of the AME may be a
      useful tool for comparing different MAs. Such comparative studies should be
      designed in a manner that provides the use of similar AUC ranges, since the AUC
      may be considered as a common pharmacokinetic denominator in comparing one MA or
      dosing regimen to another.

PMID- 9021192
TI  - Effects of benzoxazinorifamycin KRM-1648 on cytokine production at sites of
      Mycobacterium avium complex infection induced in mice.
AB  - Although various antimicrobial agents exhibit appreciable microbicidal activity
      in the early phase (weeks 2 t0 4) of Mycobacterium avium complex (MAC) infection
      induced in mice, progressive bacterial regrowth subsequently occurs. To clarify
      the reason for this pattern of changes, we studied changes in the levels of
      various cytokines in tissue at sites of infection (spleens and lungs) of MAC
      infected mice which were or were not given a benzoxazinorifamycin, KRM-1648
      (KRM). Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF
      alpha) and gamma interferon (IFN-gamma) in tissues temporarily increased at
      around weeks 2 to 4 after infection, rapidly decreased thereafter, and returned
      to normal by week 8. Similar but somewhat delayed changes were noted for levels
      of interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta),
      immunosuppressive cytokines with macrophage (M phi)-deactivating activity, in
      tissue, except that TGF-beta levels in the spleen remained high during weeks 4 to
      8. KRM treatment blocked the increase in the levels of all of those cytokines in
      tissue in the early phase of infection, most strongly at week 4. IL-6 levels were
      beneath the limit of detection throughout the observation period. Bacterial loads
      in the visceral organs decreased during the first 2 weeks, and KRM treatment
      markedly promoted this decrease. However, regrowth of MAC organisms began at
      weeks 2 to 4 and continued thereafter, even in KRM-treated mice. Splenocytes and
      splenic M phi s of MAC-infected mice (week 2) produced and/or released into the
      culture fluid significant amounts of TNF-alpha (in a cell-bound form), IFN-gamma,
      and IL-10, but not TGF-beta, during 3 days of cultivation. A substantial amount
      of TGF-beta was produced during 2 weeks of cultivation of peritoneal M phi s. KRM
      itself did not significantly affect the IL-10- and TGF-beta-producing ability of
      cultured M phi s. These findings suggest that IL-10 and TGF-beta play important
      roles in the regrowth of MAC organisms seen during the course of KRM treatment.

PMID- 9021193
TI  - The population dynamics of antimicrobial chemotherapy.
AB  - We present and analyze a series of mathematical models for the emergence of
      resistance during antibiotic treatment of an infected host. The models consider
      the population dynamics of antibiotic-sensitive and -resistant bacteria during
      the course of treatment and addresses the following problems: (i) the probability
      of obtaining a resistant mutant during the course of treatment as a function of
      antibiotic exposure; (ii) the conditions under which high, infrequent doses of an
      antibiotic are predicted to succeed in preventing the emergence of resistance;
      (iii) the conditions for the success of multiple drug treatment in suppressing
      the emergence of resistance and the relationship between antibiotic synergism and
      suppression of resistance; and (iv) the conditions under which nonadherence to
      the prescribed treatment regimen is predicted to result in treatment failure due
      to resistance. We analyze the predictions of the model for interpreting and
      extrapolating existing experimental studies of treatment efficacy and for
      optimizing treatment protocols to prevent the emergence of resistance.

PMID- 9021194
TI  - Properties of IRT-14 (TEM-45), a newly characterized mutant of TEM-type beta
      lactamases.
AB  - IRT-14 (TEM-45) is a new mutant TEM-type beta-lactamase that was isolated from
      clinical Escherichia coli P37 and that confers resistance to broad-spectrum
      penicillins with reduced sensitivity to beta-lactamase inhibitors. The MICs of
      amoxicillin alone and of amoxicillin combined with 2 micrograms of clavulanic
      acid or 2 micrograms of tazobactam per ml were 4,096, 2,048, and 1,024
      micrograms/ml, respectively. The strain was susceptible to cephalosporins,
      aztreonam, moxalactam, and imipenem. The enzyme was purified to homogeneity, and
      values of the kinetic parameters Kcat, Km, and Kcat/Km were determined for
      different substrates. This enzyme, with a pI of 5.2, was found to have reduced
      affinity for broad-spectrum penicillins and cephalosporins. The values of 50%
      inhibitory concentrations of clavulanic acid, sulbactam, tazobactam, and
      brobactam are correlated with the higher KmS for substrates. The resistance of E.
      coli P37 to mechanism-based inactivators results from a higher level of
      production of the TEM-derived enzyme due to the G-to-T substitution at position
      162 (G-162-->T) in the promoter region of blaTEM and from the structural
      modifications resulting from the Met-69-->Leu and Arg-275-->Gln substitutions
      that characterize IRT-14 beta-lactamase.

PMID- 9021195
TI  - A cytotoxicity assay for evaluation of candidate anti-Pneumocystis carinii
      agents.
AB  - A series of over 60 agents representing several different classes of compounds
      were evaluated for their effects on the ATP pools of Pneumocystis carinii
      populations derived from immunosuppressed rats. A cytotoxicity assay based on an
      ATP-driven bioluminescent reaction was used to determine the concentration of
      agent which decreased the P. carinii ATP pools by 50% versus untreated controls
      (IC50). A ranking system based on the IC50 value was devised for comparison of
      relative responses among the compounds evaluated in the cytotoxic assay and for
      comparison to in vivo efficacy. With few exceptions, there was a strong
      correlation between results from the ATP assay and the performance of the
      compound in vivo. Antibiotics, with the exception of trimethoprim
      sulfamethoxazole (TMP-SMX), were ineffective at reducing the ATP pools and were
      not active clinically or in the rat model of P. carinii pneumonia. Likewise,
      other agents not expected to be effective, e.g., antiviral compounds, did not
      show activity. Standard anti-P. carinii compounds, e.g., TMP-SMX, pentamidine,
      and dapsone, dramatically reduced ATP levels. Analogs of the quinone and
      topoisomerase inhibitor groups were shown to reduce ATP concentrations and hold
      promise for further in vivo investigation. The cytotoxicity assay provides a
      rapid assessment of response, does not rely on replicating organisms, and should
      be useful for assessment of structure-function relationships.

PMID- 9021196
TI  - Diarylsulfones, a novel class of human immunodeficiency virus type 1 integrase
      inhibitors.
AB  - A majority of reported human immunodeficiency virus type 1 integrase (HIV-1 IN)
      inhibitors are polyhydroxylated aromatic compounds containing two phenyl rings
      separated by aliphatic or aromatic linkers. Most inhibitors possessing a catechol
      moiety exhibit considerable toxicity in cellular assays. In an effort to identify
      nonhydroxylated analogs, a series of aromatic sulfones were tested for their
      ability to inhibit the 3' processing and strand transfer steps that are necessary
      for HIV replication. Several aromatic sulfones have previously been shown to have
      moderate activity against HIV-1 reverse transcriptase in cellular assays;
      however, their inhibitory potencies against IN have not been explored. In the
      present study, the inhibitory effect of a series of sulfones and sulfonamides
      against IN was determined. Among 52 diaryl sulfones tested, 4 were determined to
      be highly potent (50% inhibitory concentration [IC50], 0.8 to 10 micrograms/ml),
      5 had good potencies (IC50, 11 to 50 micrograms/ml), 10 showed moderate potencies
      (IC50, 51 to 100 micrograms/ml), and 33 were inactive (IC50, > 100 micrograms/ml)
      against IN. All of the active compounds exhibited similar potencies against HIV-2
      IN. Sulfa drugs, used extensively in treating Pneumocystis carinii pneumonia, a
      leading cause of morbidity and mortality in AIDs patients, were also examined.
      Among 19 sulfonamides tested, sulfasalazine (IC50, 50 micrograms/ml) was the most
      potent. We conclude that potent inhibitors of IN can be designed based on the
      results presented in this study.

PMID- 9021197
TI  - The human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein zinc
      ejection activity of disulfide benzamides and benzisothiazolones: correlation
      with anti-HIV and virucidal activities.
AB  - It has been shown previously by our group and others that a series of four
      disulfide benzamides with cellular anti-human immunodeficiency virus (HIV)
      activity can eject zinc from HIV type 1 nucleocapsid protein (NCp7) in vitro
      while analogs without antiviral activity do not. We also found that the zinc
      ejection activity correlates with the loss of the ability of NCp7 to bind to HIV
      psi RNA in vitro. These observations indicate that the antiviral disulfide
      benzamides may act at a novel retroviral target of action, i.e., the nucleocapsid
      protein. The present studies examine the relationship among disulfide benzamide
      structure, in vitro NCp7 zinc ejection activity, and antiviral activity for a
      larger series of compounds. All of the antiviral disulfide benzamides were found
      to eject NCp7 zinc, while some disulfide benzamides with zinc ejection activity
      are not antiviral. Utilizing the thiol reagent 5,5'-dithiobis(2-nitrobenzoic
      acid), it was determined that the o-amido-phenyl disulfides being studied cyclize
      in aqueous solution to form benzisothiazolones. A series of benzisothiazolones,
      which are stable in solution in the absence of dithiothreitol, were found to
      eject NCp7 zinc at a rate similar to that of their disulfide benzamide analogs
      and to possess similar antiviral activity. It was also found that the relative
      rates of HIV inactivation by various disulfide benzamides and benzisothiazolones
      correlate with their relative kinetic rates of NCp7 zinc ejection, which is
      consistent with the nucleocapsid protein being the target of action of these
      compounds.

PMID- 9021198
TI  - Differential distributions in tissues and efficacies of aztreonam and ceftazidime
      and in vivo bacterial morphological changes following treatment.
AB  - The differential tissue distributions of aztreonam and ceftazidime within fibrin
      clots infected with Pseudomonas aeruginosa, Enterobacter cloacae, and Serratia
      marcescens, their efficacies, and the in vivo bacterial morphological changes
      induced by these drugs were evaluated. Rabbits were given intravenously a single
      dose of 100 mg of either agents/kg of body weight. In the cores of the clots, the
      peak levels of both drugs were much lower than those observed in the peripheries
      and in serum. Aztreonam's half-lives within the peripheries and in the cores of
      the fibrin clots were up to six times higher than observed in serum, while
      ceftazidime's half-lives in clots were twice that observed in serum. This
      resulted in a much greater penetration ratio for aztreonam than for ceftazidime.
      Both drugs controlled the growth of P. aeruginosa in vivo, but E. cloacae and S.
      marcescens responded better to ceftazidime. Morphological changes were more
      abundant in the peripheries than in the cores of the clots. In the control group,
      P. aeruginosa's morphology in the cores was different than that in the
      peripheries of the clots. Against P. aeruginosa, aztreonam did induce
      morphological changes in the cores while ceftazidime did not. Electron
      microscopic studies revealed that morphological changes associated with aztreonam
      seemed different than those of ceftazidime. Along with elongation of bacteria,
      more bow tie and herniated bacteria were observed with aztreonam. Though both
      agents selectively affect PBP 3, as manifested by elongated bacteria, they induce
      in the peripheries of the clots thickening, breaks, and detachment in bacterial
      cell walls, alterations which are generally associated with antibiotics affecting
      PBP 1a and 1b.

PMID- 9021199
TI  - Hypothesis on the mechanism of resistance to fluconazole in Histoplasma
      capsulatum.
AB  - An AIDS patient with disseminated histoplasmosis who improved during treatment
      with fluconazole but remained fungemic and subsequently relapsed is described.
      Isolates obtained from blood during therapy showed a progressive increase in
      fluconazole MIC from 0.625 to 20 micrograms/ml. The pretreatment, or parent,
      isolate and the posttreatment, or relapse, isolate demonstrated identical genetic
      patterns by PCR fingerprinting with three different primers. Fluconazole was less
      potent inhibitor of the growth of the relapse isolate than of the pretreatment
      isolate (50% inhibitory concentration [IC50] = 11.7 microM), while itraconazole
      was more potent (relapse isolate IC50 = 0.0011 microM versus pretreatment isolate
      IC50 = 0.0064 microM). Neither the increased sensitivity to itraconazole nor the
      decreased activity of fluconazole on the growth of the relapse isolate results
      from changes in the intracellular content of these agents. To reach 50%
      inhibition of ergosterol synthesis in both the parent and relapse isolates, about
      2 nM itraconazole was needed; with fluconazole, 50% inhibition was achieved at
      20.9 microM and 55.5 microM, respectively. Resistance to fluconazole may develop
      during treatment and results from decreased sensitivity of ergosterol synthesis.

PMID- 9021200
TI  - In vitro evaluation of antibiotic diffusion from antibiotic-impregnated
      biodegradable beads and polymethylmethacrylate beads.
AB  - Antibiotic-impregnated beads are used in the dead bone space following
      debridement surgery to deliver local, high concentrations of antibiotics.
      Polymethylmethacrylate (PMMA), 2,000-molecular-weight (MW) polylactic acid (PLA),
      Poly(DL-lactide)-coglycolide (PL:CG; 90:10, 80:20, and 70:30), and the
      combination 2,000-MW PLA-70:20 PL:CG were individually mixed with clindamycin,
      tobramycin, or vancomycin. Beads were placed in 1 ml of phosphate-buffered saline
      (PBS) and incubated at 37 degrees C. The PBS was changed daily, and the removed
      PBS samples were stored at -70 degrees C until the antibiotic in each sample was
      determined by microbiological disk diffusion assay. Nondissolving PMMA beads with
      tobramycin and clindamycin had concentrations well above breakpoint sensitivity
      concentrations (i.e., the antibiotic concentrations at the transition point
      between bacterial killing and resistance to the antibiotic) for more than 90
      days, but vancomycin concentrations dropped by day 12. ALl PLA, PL:CG, and the
      2,000-MW PLA-70:30 PL:CG biodegradable beads release high concentrations of all
      the antibiotics in vitro for the period of time needed to treat bone infections
      (i.e., 4 to 8 weeks). Antibiotic-loaded PLA and PL:CG beads have the advantage of
      better antibiotic elution and the ability to biodegradable (thereby averting the
      need for secondary surgery for bead removal) compared to the PMMA beads presently
      used in the clinical setting.

PMID- 9021201
TI  - Inhibition of multiple phases of human immunodeficiency virus type 1 replication
      by a dithiane compound that attacks the conserved zinc fingers of retroviral
      nucleocapsid proteins.
AB  - The human immunodeficiency virus type 1 (HIV-1) nucleocapsid p7 protein contains
      two retrovirus-type zinc finger domains that are required for multiple phases of
      viral replication. Chelating residues (three Cys residues and one His residue) of
      the domains are absolutely conserved among all strains of HIV-1 and other
      retroviruses, and mutations in these residues in noninfectious virions. These
      properties establish the zinc finger domains as logical targets for antiviral
      chemotherapy. Selected dithiobis benzamide (R-SS-R) compounds were previously
      found to inhibit HIV-1 replication by mediating an electrophilic attack on the
      zinc fingers. Unfortunately, reaction of these disulfide-based benzamides with
      reducing agents yields two monomeric structures (two R-SH structures) that can
      dissociated and no longer react with the zinc fingers, suggesting that in vivo
      reduction would inactivate the compounds. Through an extensive drug discovery
      program of the National Cancer Institute, a nondissociable tethered dithiane
      compound (1,2-dithiane-4,5-diol, 1,1-dioxide, cis; NSC 624151) has been
      identified. This compound specifically attacks the retroviral zinc fingers, but
      not other antiviral targets. The lead compound demonstrated broad antiretroviral
      activity, ranging from field isolates and drug-resistant strains of HIV-1 to HIV
      2 and simian immunodeficiency virus. The compound directly inactivated HIV-1
      virions and blocked production of infectious virus from cells harboring
      integrated proviral DNA. NSC 624151 provides a scaffold from which medicinal
      chemists can develop novel compounds for the therapeutic treatment of HIV
      infection.

PMID- 9021202
TI  - Effects of some excitatory amino acid antagonists and drugs enhancing gamma
      aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice.
AB  - The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone
      derivative, were studied after intraperitoneal (i.p.) administration to Dilute
      Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound
      induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA)
      antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some
      compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against
      seizures induced by PEFLO were also evaluated. The present study demonstrated
      that both groups of compounds administered i.p. or intracerebroventricularly were
      able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)
      alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL
      82.0715), two compounds acting on the polyamine site of the NMDA receptor
      complex, were unable to provide any protection. The relationship between the
      different sites of action and the anticonvulsant activities of these derivatives
      were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be
      easily determined, potential interactions with the receptors of EAA exist. In
      fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were
      able to increase the threshold for the seizures or to prevent the seizures
      induced by PEFLO, while compounds acting at the polyamine site did not provide
      any protection. The AMPA-KA receptor antagonists were also able to exert
      anticonvulsant activity, but with minor potency in comparison to those of NMDA
      antagonists. In addition, the fact that compounds enhancing GABA-ergic
      neurotransmission were also able to protect the mice against seizures induced by
      PEFLO suggests an involvement of GABA system.

PMID- 9021203
TI  - Comparison of the bactericidal activities of piperacillin-tazobactam, ticarcillin
      clavulanate, and ampicillin-sulbactam against clinical isolates of Bacteroides
      fragilis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa.
AB  - Owing to the broad spectrum of activity afforded by beta-lactam-beta-lactamase
      inhibitor preparations, these agents are frequently selected as empiric therapy
      for the treatment of mixed infections such as intra-abdominal and diabetic foot
      infections, either alone or in combination with an aminoglycoside. Twelve healthy
      volunteers were enrolled in a randomized, open-label, four-way crossover trial
      comparing the bactericidal activities of piperacillin-tazobactam, ticarcillin
      clavulanate, and ampicillin-sulbactam against microorganisms commonly isolated
      from mixed infections. Subjects received the following regimes: (i) 3.375 g of
      piperacillin-tazobactam intravenously (i.v.) every 6 h (q6h) (ii) 4.5 g of
      piperacillin-tazobactam i.v. q8h, (iii) 3.1 g of ticarcillin-clavulanate i.v.
      q6h, and (iv) 3.0 g of ampicillin-sulbactam i.v. q6h. Serum bactericidal titers
      were determined and used to calculate the duration of measurable bactericidal
      activity over the dosing interval of each of the regimens against two clinical
      isolates of Bacillus fragilis, Escherichia coli, Enterococcus faecalis, and
      Pseudomonas aeruginosa. The percentage of the dosing interval over which drug
      concentrations in serum remained above the MIC for each organism was determined
      and compared with the observed duration of bactericidal activity was noted (r =
      0.78; P < 0.001). All of the regimens demonstrated good activity against B.
      fragilis and E. coli. Against E. faecalis and P. aeruginosa, however, all of the
      regimens provided bactericidal activity for less than 50% of the respective
      dosing intervals. These data suggest that use of shorter dosing intervals or
      continuous-infusion regimens should be considered in combination with an
      aminoglycoside to improve the bactericidal profiles of these agents for E.
      faecalis and P. aeruginosa.

PMID- 9021204
TI  - Expression of Escherichia coli TehA gives resistance to antiseptics and
      disinfectants similar to that conferred by multidrug resistance efflux pumps.
AB  - The genes tehAB located at 32.3 min on the Escherichia coli chromosome were
      initially identified by their ability to mediate resistance to potassium
      tellurite (128 micrograms of K2TeO3 per ml) when overexpressed with a high-copy
      number plasmid. The genes encode an integral membrane protein (TehA) of 36 kDa
      with 10 putative transmembrane segments and a second protein (TehB) of 23 kDa.
      Overexpression of TehAB results in hypersensitivity to dequalinium CI and methyl
      viologen (paraquat). Expression of TehA alone gives similar hypersensitivity.
      Overexpression of TehA gave resistance to tetraphenylarsonium CI, ethidium
      bromide, crystal violet and proflavin. The efflux of ethidium, measured by
      fluorescence quenching, revealed that TehA transported ethidium at twice the
      control rate and 10% of the rate of the highly resistant efflux transporter Emr
      Eco. Addition of tellurite had no effect on ethidium transport. In addition to
      the ethidium transport assay, a proflavin fluorescence assay which was
      approximately 200-fold more sensitive was also used. TehA was also found to have
      proflavin efflux activity. The addition of TeO32- to the proflavin transport
      assay on TehA caused a 20% increase in transport rate. Both ethidium and
      proflavin transport were found to be energy dependent.

PMID- 9021205
TI  - Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.
AB  - Cefuroxime is commercially available for parenteral administration as a sodium
      salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester
      of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any,
      antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the
      absorption of cefuroxime axetil in the small intestines of anesthetized rats was
      investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200
      microM). Oral absorption of cefuroxime axetil can apparently be described as a
      specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters
      characterizing absorption of prodrug in free solution were obtained: maximum rate
      of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17
      microM. Cefuroxime axetil transport was significantly reduced in the presence of
      the enzymatic inhibitor sodium azide. On the other hand, the prodrug was
      metabolized in the gut wall through contact with membrane-bound enzymes in the
      brush border membrane before absorption occurred. This process reduces the
      prodrug fraction directly available for absorption. From a bioavailability point
      of view, therefore, the effects mentioned above can explain the variable and poor
      bioavailability following oral administration of cefuroxime axetil. Thus, future
      strategies in oral cefuroxime axetil absorption should focus on increasing the
      stability of the prodrug in the intestine by modifying the prodrug structure
      and/or targeting the compound to the absorption site.

PMID- 9021206
TI  - Modeling of the change in CD4 lymphocyte counts in patients before and after
      administration of the human immunodeficiency virus protease inhibitor indinavir.
AB  - We investigated the relationships between changes in CD4 lymphocytes counts over
      24 weeks after the initiation of therapy with indinavir at dosages of > or = 2.4
      g/day (n = 15) in human immunodeficiency virus-positive patients and compared
      them to the baseline values. Starting CD4 count were linked to the time-weighted
      average CD4 cell count (return) through a nonlinear effect model. The diminution
      of destruction of CD4 cells after the initiation of indinavir therapy was
      estimated by fitting simultaneous differential equations to the data by using a
      linked lymph node (LN)-blood (BL) (two-compartment) system in which there is a
      constant rate of generation (R), first-order transfer rate constants (KLN-BL and
      KBL-LN) of compartment exchange, and first-order rate constants of CD4
      destruction in the absence and presence of indinavir (KLN-OUT1 and KLN-OUT2). The
      half-life of CD4 lymphocytes was calculated from the rate constants by standard
      two-compartment methods. The CD4 lymphocyte counts at the start and return were
      linked in a sigmoid-Emax model were the maximal effect (Emax) was at 574.6
      cells/microliters and 50% of the effect occurred at 157.1 cells/microliters (r2 =
      0.94; P < 0.001). The mean +/- standard deviation (median) KLN-OUT2 was 0.574 +/-
      0.202 (0.589), indicating that indinavir decrease the destruction of CD4 cells by
      circa 41 to 42%. The mean (median) CD4 half-life was 11.5 +/- 5.72 day (10.3
      days). In multivariate analysis, KLN-OUT2 was significantly correlated with
      starting the CD4 cells count and the change in the CD4 cell count on therapy. The
      relationship between CD4 lymphocyte half-life and the starting CD4 lymphocyte
      count was hyperbolic, with a rapid increase in half-life as the CD4 count
      decreased. On the basis of the calculated half-life, the average production
      (destruction) of CD4 lymphocytes was approximately 3 x 10(9) cells/day, with an
      individual variation of 44-fold. These findings suggest that (i) the CD4
      lymphocyte cell count at the start is significantly correlated to both the
      decrease in the destruction rate of CD4 cells and the degree of change in the CD4
      lymphocytes on therapy, (ii) the lower the initial CD4 lymphocyte count, the
      higher the amount of CD4 lymphocyte turnover and the lower the ability of the
      immune system to increase absolute CD4 lymphocyte levels after viral suppression,
      consistent with a decreased regenerative capacity with progression of disease;
      and (iii) the increase in CD4 lymphocytes is likely secondary to the expansion of
      proliferating pool of cells since our determinations are based on 24 weeks of
      effect.

PMID- 9021207
TI  - In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004.
AB  - Ketolides, a novel macrolide subclass, possess a mode of action that is similar
      to that of structurally related macrolide-lincosamide-streptogramin (MLS)
      compounds. By using reference in vitro tests, the in vitro activity of RU-64004
      was compared to those of six other MLS compounds against more than 800 clinical
      pathogens, including 356 gram-positive organisms. The spectrum of activity of the
      ketolide was most similar to that of clindamycin versus staphylococci and
      streptococci and superior to those of all macrolides tested against oxacillin
      resistant staphylococci and vancomycin-resistant (vanA, vanB, and vanC)
      enterococcal isolates. The activity of the ketolide was greater than those of the
      macrolides, azalides, or clindamycin tested against vancomycin-susceptible
      enterococci (MICs at which 90% of isolates are inhibited [MIC90S], 0.25 to 4
      micrograms/ml), penicillin-resistant pneumococci (MIC90, 0.25 micrograms/ml), and
      most beta-hemolytic streptococci. All Streptococcus pneumoniae and beta-hemolytic
      streptococcus strain were inhibited by ketolide concentrations of < or = 0.25
      micrograms/ml. Against 165 erythromycin-resistant strains, RU-64004 inhibited
      (MICs, < or = 0.5 micrograms/ml) approximately one-third of staphylococci, all
      streptococci, and slightly more than one-half of the enterococci. Quinupristin
      dalfopristin (a streptogramin combination) was active against all tested isolates
      with the exception of non-Enterococcus faecium enterococci, against which the
      ketolide exhibited greater potency (MIC50S, 0.03 to 2 micrograms/ml). The
      ketolide was also active against Haemophilus influenzae (MIC90, 2 micrograms/ml),
      Moraxella catarrhalis (MIC90, 0.12 micrograms/ml), pathogenic Neisseria spp.
      (MIC90, 0.5 micrograms/ml), and many gram-positive anaerobes (MIC90, 0.5
      micrograms/ml). RU-64004 may enhance the role of macrolide drugs in the treatment
      of some serious infections caused by MLS-resistant gram-positive organisms.

PMID- 9021208
TI  - Increased activation of the combination of 3'-azido-3'-deoxythymidine and 2'
      deoxy-3'-thiacytidine in the presence of hydroxyurea.
AB  - The intracellular phosphorylation of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'
      thiacytidine was increased two- to threefold by the addition of hydroxyurea (HU)
      to the single drugs or to the two drugs in combination. The ratios of drug
      triphosphate to competing cellular deoxynucleoside triphosphate were increased
      two- to threefold for both 3'-azido-3'-deoxythymidine and 2'-deoxy-3'
      thiacytidine in the presence of HU. These HU-induced increases in 3'-azido-3'
      deoxythymidine and 2'-deoxy-3'-thiacytidine metabolism may further enhance the
      anti-human immunodeficiency virus activity of these two drugs.

PMID- 9021209
TI  - In vitro activities of the oxazolidinone antibiotics U-100592 and U-100766
      against Staphylococcus aureus and coagulase-negative Staphylococcus species.
AB  - U-100592 and U-100766 are closely related antibiotics of the oxazolidinone class.
      Their in vitro activities were determined against 100 isolates of Staphylococcus
      aureus and 100 isolates of coagulase-negative Staphylococcus species by broth and
      agar dilution test methods. The MICs of both compounds by either test method at
      which 50 and 90% of isolates are inhibited were 2 and 4 micrograms/ml,
      respectively, for S. aureus and 1 to 2 micrograms/ml for coagulase-negative
      staphylococci. Time-kill assay with selected strains indicated a primarily
      bacteriostatic effect against staphylococci.

PMID- 9021210
TI  - Transferable hyperproduction of TEM-1 beta-lactamase in Shigella flexneri due to
      a point mutation in the pribnow box.
AB  - TEM-1 hyperproduction in two ampicillin-sulbactam-resistant Shigella flexneri
      strains was studied. In both strains the blaTEM gene was encoded as a single copy
      on a large conjugatively transferable plasmid. A single G-->T transversion at
      position 1 of the -10 consensus sequence was identified to be the mechanism of
      TEM-1 hyperproduction.

PMID- 9021212
TI  - Comparative evaluation of the inhibitory activities of the novel penicillanic
      acid sulfone Ro 48-1220 against beta-lactamases that belong to groups 1, 2b, and
      2be.
AB  - The inhibitory activity of the penicillanic acid sulfone Ro 48-1220 against group
      1, 2b, and 2be beta-lactamases was evaluated. Ro 48-1220 inhibited TEM and SHV as
      effectively as clavulanate and tazobactam. It also inhibited group 1 beta
      lactamases at lower concentrations than tazobactam. Ro 48-1220, at a
      concentration of 4 micrograms/ml, protected ceftriaxone and ceftazidime against
      strains producing group 1 and 2be beta-lactamases.

PMID- 9021211
TI  - Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective
      targeting of gyrase or topoisomerase IV by quinolones.
AB  - gyrA and parC mutations have been identified inn Streptococcus pneumoniae mutants
      stepwise selected for resistance to sparfloxacin, an antipneumococcal
      fluoroquinolone. GyrA mutations (at the position equivalent to resistance hot
      spot Ser-83 in Escherichia coli GyrA) were found in all 17 first-step mutants
      examined and preceded DNA topoisomerase IV parC mutations (at Ser-79 or Glu-83),
      which appeared only in second-step mutants. The targeting of gyrase by
      sparfloxacin in S. pneumoniae but of topoisomerase IV by ciprofloxacin indicates
      that target preference can be altered by changes in quinolone structure.

PMID- 9021213
TI  - Trovafloxacin, a new fluoroquinolone with potent activity against Streptococcus
      pneumoniae.
AB  - An in vitro study of the activity of 15 antibacterial agents against 202 recent
      pediatric isolates of Streptococcus pneumoniae from urban and rural Nebraska and
      rural Kentucky identified trovafloxacin, ofloxacin, clindamycin, and vancomycin
      as the most active agents and equally active against both penicillin-susceptible
      and--resistant strains. In contrast, six beta-lactams, three macrolides, and
      trimethoprim-sulfamethoxazole were less active overall, especially against
      penicillin-intermediate and--resistant strains. Trovafloxacin inhibited all
      strains at a concentration of < or = 0.25 micrograms/ml and was 8- to 16-fold
      more potent than ofloxacin or ciprofloxacin.

PMID- 9021215
TI  - Comparative in vitro activities of trovafloxacin (CP 99,219) and other
      antimicrobials against clinically significant anaerobes.
AB  - A total of 590 strains of clinically important anaerobes were tested to determine
      their susceptibility to trovafloxacin. Overall, trovafloxacin had a mode MIC of
      0.25 micrograms/ml and a MIC at which 90% of the isolates were inhibited of 1
      micrograms/ml and had activity comparable to that of metronidazole. Trovafloxacin
      was 8-, 8-, 16-, 32-, and 64-fold more active than ampicillin-sulbactam,
      clindamycin, ciprofloxacin, cefoxitin, and cefotetan, respectively. Of the
      Bacteroides fragilis group, 97% of the isolates were inhibited by trovafloxacin
      at 21 micrograms/ml, and trovafloxacin was more active than ciprofloxacin,
      cefoxitin, cefotetan, ampicillin-sulbactam, and clindamycin against Clostridium,
      Fusobacterium, Porphyromonas, and Prevotella strains.

PMID- 9021214
TI  - Fungicidal activity of cecropin A.
AB  - Cecropin A (CA) fungicidal properties were explored. Nongerminated and germinated
      Aspergillus spp. and Fusarium spp. conidia were treated with CA. CA achieved
      complete lethality at < or = 25 microM (99 micrograms/ml) for germinating, but
      not nongerminating, conidia of Aspergillus spp. CA achieved total lethality for
      nongerminated and germinating conidia of Fusarium spp at 1.5 microM (6
      micrograms/ml). MIC and minimal lethal concentration assays in buffered RPMI
      medium gave similar results.

PMID- 9021216
TI  - In vitro activity and spectrum of LY333328, a novel glycopeptide derivative.
AB  - Reference methods were used to determine the potency of LY333328, a semisynthetic
      glycopeptide derivative with a key N-alkylation substitution, against 833 strains
      (393 gram-positive strains and representative gram-negative bacilli) with various
      defined resistance mechanisms. The MICs at which 90% of the isolates are
      inhibited (MIC90S) (in micrograms per milliliter) of LY333328 and the percentages
      of strains at < or = 8 micrograms/ml were as follows: for oxacillin-susceptible
      Staphylococcus aureus, 2 and 100%, and for oxacillin-resistant Staphylococcus
      aureus, 4 and 100%; for oxacillin-susceptible Staphylococcus epidermis, 4 and
      100%, and for oxacillin-resistant Staphylococcus aureus, 8 and 96%; for
      Streptococcus serogroups A, B, C, and G, 0.25 to 1 and 100%; for Streptococcus
      pneumoniae < or = 0.015 to 0.06 and 100%; for Enterococcus faecalis, 2 and 100%;
      and for vancomycin-susceptible Enterococcus faecium, 0.25 and 100%, and for
      vancomycin-resistant Enterococcus faecium, 4 and 100%. LY333328 was not active
      (MIC50, > or = 16 micrograms/ml) against more than 400 representative strains of
      Enterobacteriaceae, pseudomonads, Acinetobacter spp., Stenotrophomonas
      maltophilia, Haemophilus influenzae, Moraxella catarrhalis, pathogenic Neisseria
      spp., and anaerobic gram-negative bacilli. Gram-positive anaerobes were LY333328
      susceptible (MICs, < or = 2 micrograms/ml). Test methods and conditions may have
      affected MICs of LY333328, with most (species variation) agar dilution MICs being
      greater than the broth microdilution MICs.

PMID- 9021217
TI  - Change in prevalence and antibiotic resistance of Enterococcus species isolated
      from blood cultures over an 8-year period.

PMID- 9021233
TI  - Incidence and studies on antigenic specificities of antineutrophil-cytoplasmic
      autoantibodies (ANCA) in poststreptococcal glomerulonephritis.
AB  - Sera from 210 patients with Acute Poststreptococcal Glomerulonephritis (APSGN)
      and 14 patients with streptococcal impetigo without glomerular disease were
      tested for the presence of IgG-ANCA using an indirect immunofluorescence assay
      (IIF) on ethanol fixed normal human neutrophils. In the group of nephritic
      patients, ANCA were detected by IIF in 9% (18 out of 210 cases) in an atypical
      diffuse cytoplasmic pattern (a-ANCA) in 14 cases and in a (p-ANCA) perinuclear
      staining in the remaining 4 cases. Longitudinal studies performed on six IIF
      positive patients, showed persistence of the phenomenon for up to six months,
      without relationship with activity of disease. No patient with streptococcal
      impetigo showed positivity on the IIF assay. Positive sera were analyzed on ELISA
      plates for their IgG reactivity against specific purified ANCA antigens:
      Proteinase-3 (PR3), Myeloperoxidase (MPO). Cathepsin-G and
      Bactericidal/Permeability Increasing Protein (BPI). Anti-MPO antibodies were
      present in 4 cases (3 a-ANCA and 1 p-ANCA). No reactivity was identified against
      PR-3, BPI and Catepsin-G in any of the samples. The presence of ANCA was
      significantly associated with a more severe glomerular disease as assessed by the
      serum creatinine and the crescents formation. Further studies are required to
      identify other antigenic specificities of these autoantibodies. Their absence in
      the streptococcal impetigo control group might suggest that their presence in
      APSGN could play some pathogenic role in kidney disease.

PMID- 9021234
TI  - Circulating levels of cytokines in poststreptococcal glomerulonephritis.
AB  - Cellular immune mechanisms are important in the pathogenesis of acute
      glomerulonephritis, as underlined by recent demonstrations of cytokine activity
      in the urine and in the renal tissue of some of these patients. Therefore, we
      decided to study circulating levels of IL-6, TNF alpha and PDGF measured by ELISA
      in 12 patients with acute poststreptococcal glomerulonephritis (PSGN) on
      admission, at the time of discharge from the hospital, 45 days and 3 months
      later. We also studied 9 patients with acute streptococcal pharyngitis without
      nephritis, during acute infection, 8 and 21 days later and 20 normal children
      (control group). On admission, patients with PSGN had increased IL-6 levels (12.4
      +/- 4 pg/ml vs control = 2.57 +/- 0.34 pg/ml, p < 0.05) which returned to normal
      at the time of discharge from the hospital, 8 to 17 days later. TNF alpha was
      also elevated in the acute phase (8.11 +/- 1.19 pg/ml vs 3.74 +/- 1.4 pg/ml in
      controls, p < 0.005) but significant individual variation was detected in serial
      determinations. Levels of PDGF were always normal. In acute streptococcal
      tonsillitis without nephritis, IL-6 and TNF alpha were increased at the time of
      active infection, but levels of IL-6 fell to the normal range after 1 week while
      the increase observed in association with PSGN develops 2 to 3 weeks after
      infection and followed the clinical course of the disease.

PMID- 9021235
TI  - Pathogenetic aspects of uncomplicated urinary tract infection: recent advances.
AB  - Urinary tract infections mostly are caused by Enterobacteriaceae; E. coli
      dominating in 80-90% for uncomplicated diseases. Microorganisms possessing the
      ability to colonize the uroepithelium (fimbriae/pili) and to cytotoxically damage
      cells and tissue (hemolysin) may initiate acute infection. Properties such as
      serum resistance, iron sequesteration, hydroxamate production and the presence of
      K-antigen are found in strains which persist in the host without initiating
      clinical symptoms. The ability of bacteria to adhere to cells of the epithelial
      boundary layer of the host organisms is of initial importance in the origin and
      progress of an infection. A variety of specific factors, e.g. glycolipids on the
      surface of the uroepithelium as well as cellular and humoral disorders of
      immunoreactions in the host determine the course of a disease. The immune
      response may ameliorate clinical symptoms and select urovirulent characteristics
      of the causative microorganism in recurrent diseases.

PMID- 9021237
TI  - Clinical and biochemical patterns of presentation in monolateral and bilateral
      calcium nephrolithiasis.
AB  - To investigate patterns of monolateral and bilateral nephrolithiasis, we enrolled
      196 patients with idiopathic calcium stone disease (ICaSD) and 36 with proven
      primary hyperparathyroidism (PHP). Monolateral disease occurred in 45 subjects
      with ICaSD and 3 with PHP. All had had three or more stone events. They were
      studied for a number of clinical and biochemical parameters. The expected
      prevalence of monolateral stone disease was calculated according to the binomial
      distribution of random events. Whereas the observed and expected prevalence of
      monolateral nephrolithiasis did not differ in PHP, the distribution did not
      follow a chance pattern in ICaSD, since monolateral disease was still frequent
      among patient with more than 6 episodes. To find out whether monolateral and
      bilateral ICaSD had distinct pathogenic mechanisms the two groups were compared
      for clinical and biochemical patterns: no differences emerged concerning
      metabolic derangements, urine saturation and diet-related biochemistries.
      Bilateral stone-formers had a higher recurrence rate, but a similar number of
      stone-operations or ESWL. In 81 of 151 bilateral idiopathic stone-formers in
      which we were able to assess the exact number of stone events in left and right
      kidney, the distribution of stones between kidneys did not differ from the
      binomial distribution. In conclusion, while PHP-associated nephrolithiasis
      presents predictable patterns, ICaSD comprises a subset in which the disease
      occurs monolaterally. These forms cannot be distinguished from bilateral forms
      with common clinical features or routine biochemistries.

PMID- 9021236
TI  - Ultrasonographic study of pancreatic cysts in autosomal dominant polycystic
      kidney disease.
AB  - Pancreatic cysts are an uncommon extrarenal clinical feature of autosomal
      dominant polycystic kidney disease (ADPKD). The prevalence of pancreatic cysts,
      sonographically assessed in ADPKD and in the different typs of ADPKD (PKD1 and
      PKD2) has not been reported. We have studied 173 ADPKD patients and 160 non
      affected family members and found a prevalence of pancreatic cysts, of 9% in
      ADPKD patients over 30 years of age. The presence of pancreatic cysts was related
      to the increasing age, to the female sex and to the type of ADPKD, found
      exclusively in PKD1 patients. No complications related to pancreatic cysts were
      recorded. Pancreatic cysts are an unusual feature of ADPKD and do not appear to
      contribute to morbidity or mortality.

PMID- 9021238
TI  - Increased plasma guanylin levels in patients with impaired renal function.
AB  - Guanylin, a 15-amino acid peptide, activates intestinal guanylate cyclase C
      receptor, thereby regulating intestinal fluid and electrolyte transport through
      the second messenger, cyclic GMP. To examine the role of the kidney in guanylin
      metabolism, we used a radioimmunoassay (RIA) to measure plasma concentrations of
      guanylin in 3 groups; normal individuals, patients who had renal disorders with
      normal or elevated serum creatinine levels (0.4 < Cre < 11.9 mg/dl), and patients
      who received hemodialysis (HD). The plasma concentration of immunoreactive
      guanylin in the normal individuals was 32.3 +/- 4.8 fmol/ml. The concentrations
      in 32 non-HD patients were correlated with their serum creatinine concentrations
      (r = 0.81, p < 0.0001). In 16 HD patients the plasma concentrations of
      immunoreactive guanylin before the start of HD were correlated with their
      dialysis duration (r = 0.63, p < 0.01). The plasma levels of immunoreactive
      guanylin in HD patients for whom EVAL membranes were used decreased one hour
      after the start of HD as compared with the prior levels. The plasma levels in HD
      patients for whom PC membranes were used showed no change. Ten kilodalton
      guanylin is the main component of guanylin molecules in the plasma and
      hemofiltrates of HD patients. These findings suggest that the kidney has a major
      role in the elimination and/or metabolism of guanylin. Uroguanylin, a member of
      the guanylin family that was recently isolated from human urine, also acts on the
      guanylate cyclase C receptor. Further studies of guanylin family peptides should
      provide a better understanding of the physiological roles of the kidney in the
      control of water and electrolyte balance.

PMID- 9021239
TI  - Effect of nifedipine on renal allograft function and survival beyond one year.
AB  - We previously reported that a calcium channel blocker supplemented
      immunosuppression produced excellent patient and graft survival rates in
      cadaveric kidney transplantation. We report here the long term outcome of
      patients treated with nifedipine-supplemented triple immunosuppression as
      compared with those of historical controls who were treated similarly without
      nifedipine. Study subjects included 111 patients transplanted in 1990-1994,
      treated with nifedipine and triple immunosuppression and with functioning grafts
      for more than one year (Nifedipine group). The results of cyclosporine (CyA)
      dose, blood pressure (BP), serum creatinine (Cr), and actuarial graft survival
      rate (GSR) up to 5 years posttransplant in these patients were compared with
      those of 52 patients transplanted in 1985-1990, treated similarly without calcium
      channel blockers (Control group). Donor sources, gender ratio, age distribution,
      causes of end stage renal disease, incidence of hypertension prior to
      transplantation and incidence of rejection in the first year between the groups
      were comparable. Throughout the study period the Nifedipine group had
      significantly lower serum Cr (1.5 +/- 0.7 vs. 1.8 +/- 0.7 mg/dl) and higher GSR
      (93.8% vs. 88% at 5 years) than the Control group. BP was comparable despite
      higher CyA doses in the Nifedipine group (4.3 +/- 1.1 vs. 3.3 +/- 1.1 mg/kg/day).
      We conclude that nifedipine is beneficial in improving long-term graft function
      and survival in kidney transplant recipients by mitigating CyA associated renal
      injury.

PMID- 9021240
TI  - Plasma concentrations of vitamin C, vitamin E and/or malondialdehyde as markers
      of oxygen free radical production during hemodialysis.
AB  - To investigate the effects of neutrophil activation during hemodialysis (HD),
      blood markers of oxygen free radical (OFR) activity were studied. Two groups of
      HD patients on standard cuprophane treatment were investigated after an overnight
      fast. In the first group (mean age 68 +/- 8 years; n = 6) vitamin supplementation
      was withdrawn two weeks prior to the study, whereas the second group (mean age 73
      +/- 3 years; n = 7) continued their normal vitamin intake. The two control
      groups, one consisting of age-matched subjects (mean age 72 +/- 2 years; n = 21),
      the other of younger subjects (mean age 36 +/- 7 years; n = 11), were asked to
      cease vitamin supplementation two weeks before the study and to fast overnight
      before blood sampling. Serial blood and dialysate samples were collected during
      HD in the vitamin-deprived patient group, and a single blood sample was collected
      in the other three groups. Plasma concentrations of vitamin C (total and reduced
      form), vitamin E (alpha-tocopherol) and malondialdehyde (MDA) were determined
      with newly adopted and validated HPLC methods. Basal plasma vitamin C
      concentrations were lower among vitamin-deprived HD patients than among age
      matched controls or vitamin-supplemented HD patients (22 +/- 6 microM versus 39
      +/- 19 microM and 34 +/- 10 microM, respectively). During a 3-hour HD session,
      the mean decrease in total vitamin C was 40%. Basal alpha-tocopherol
      concentrations did not differ significantly between vitamin-deprived HD patients
      and vitamin-supplemented HD patients or age-matched controls (39 +/- 5 microM
      versus 40 +/- 11 microM and 38 +/- 6 microM, respectively), but were lower in
      younger controls (33 +/- 4 microM). No alpha-tocopherol was detected in the
      dialysate, and its plasma concentration did not change significantly during a
      single HD session. Basal plasma MDA concentrations were higher in vitamin
      supplemented HD patients than in vitamin-deprived HD patients or age-matched
      controls (1.5 +/- 0.2 microM versus 0.9 +/- 0.2 microM and 1.1 +/- 0.2 microM,
      respectively). No MDA was detected in the dialysate, and its plasma concentration
      did not change significantly during a single HD session. Our results indicate an
      increased need of vitamin C supplementation in HD patients. The concentration of
      oxidized vitamin C seems to peak early during HD and may be of value as a marker
      of OFR production. alpha-tocopherol concentrations do not change during HD and do
      not differ from those in control subjects. MDA may increase over a longer period
      of time on dialysis, but does not change during a single HD treatment.

PMID- 9021242
TI  - Does pyuria indicate infection in asymptomatic dialysis patients?
AB  - It has been suggested that the finding of leukocyturia > 10 WBC/HPF in
      asymptomatic dialysis patients predicts a positive urine culture and hence
      indicates urinary tract infection. Seventeen asymptomatic ESRD patients
      contributed clean catch specimens. Nine patients had ten or more WBC/HPF. One of
      these grew a possible pathogen in pure culture (23% of specimens excluding those
      growing multiple organisms). Thus, leukocyturia is not a good marker for positive
      urine culture and moreover is not demonstrated to indicate infection even when
      positive cultures follow.

PMID- 9021241
TI  - Phlebotomy for pulmonary edema in dialysis patients.
AB  - STUDY OBJECTIVE: To assess the efficacy of phlebotomy in the treatment of
      pulmonary edema in hemodialysis patients. PROCEDURE: Maintenance hemodialysis
      patients presenting to the emergency room in respiratory distress from apparent
      pulmonary edema were assessed with regard to clinical response, change in blood
      pressure, change in hematocrit, and interval until the next hemodialysis
      treatment, RESULTS: Twenty-one patients underwent phlebotomy and seventeen
      improved markedly and did not require intubation or emergent dialysis.
      Hemodialysis was initiated 15.6 +/- 13.6 SD hours later. Four were able to have
      their treatment 24 or more hours later. Thirteen of 21 (62%) were hypertensive at
      the time of treatment and blood pressure tended to normalize in this subset. Four
      of 21 (19%) developed transient hypotension without permanent sequelae. Pre-mean
      hematocrit = 25.0 + 6.0 and post phlebotomy = 22.6 + 4.6 SD. All patients
      receiving phlebotomy survived to hospital discharge. CONCLUSION: Phlebotomy can
      often obviate the need for intubation or emergent dialysis in ESRD patients
      presenting with pulmonary edema.

PMID- 9021243
TI  - Measurement of total body water and urea kinetic modelling in peritoneal
      dialysis.
AB  - Studies of the effect of Kt/V (urea) on prediction of outcome in patients on
      peritoneal dialysis have shown conflicting results. We performed this study to
      examine the effects of the measurement of V by varying techniques on the
      calculation of Kt/V, using body water estimated by deuterium oxide dilution (D2O
      dilution) as the criterion method for estimation of V. Studies were performed in
      20 peritoneal dialysis patients. Kt was calculated from 24-hour dialysate and
      urine collections and V estimated by D2O dilution, Watson formulae, 58% of body
      weight, bioelectrical impedance (BIA) and 73% of fat-free mass estimated by DEXA.
      V was also measured in 35 healthy controls. Hydration, expressed as body water by
      D2O dilution as a percentage of fat-free mass estimated by DEXA did not differ
      between peritoneal dialysis patients 71.0 (4.9)% and a healthy control group 71.1
      (5.0)%. Mean Kt/V using D2O dilution was 2.14 (0.36). The other techniques
      resulted in a significantly lower Kt/V; Watson equations 2.01 (0.35), p < 0.005,
      BIA 1.93 (0.31), p < 0.0001, DEXA 2.06 (0.28), p < 0.05, 58% body weight 1.83
      (0.38), p < 0.0001. Limits of agreement of Kt/V by the simpler techniques
      compared with D2O dilution [mean difference of (other techniques -D2O dilution)
      as % of mean values +/- 95% limits of agreement] were Watson equation -5.9 +/-
      15.3%, BIA -10.1 +/- 15.5%, DEXA -3.4 +/- 13.5% and 58% body weight -9.9 +/-
      23.5%. Differences in Kt/V from estimates using D2O dilution were significantly
      negatively correlated with body fat for 58% body weight (r = -0.80, p < 0.0001)
      and the Watson formulae (r = -0.49, p < 0.05) but not for BIA or DEXA. We
      conclude that clinically significant variation in Kt/V may occur due to the
      estimation of V and may account for the uncertainty of the value of Kt/V as a
      predictor of outcome in peritoneal dialysis patients. Estimating V by BIA and
      DEXA did not have any benefit over the Watson formulae in terms of agreement with
      D2O dilution, though did avoid systematic errors related to body fat. Estimation
      of V as a fixed proportion of body weight is clearly inferior to the other
      techniques.

PMID- 9021244
TI  - Successful outcome of treating hemolytic uremic syndrome associated with cancer
      chemotherapy with immunoadsorption.

PMID- 9021245
TI  - Successful management of steroid-resistant nephrotic syndrome using ibuprofen.
AB  - We report the first case of the use of ibuprofen for the management of steroid
      resistant nephrotic syndrome. A 41 year-old man with nephrotic syndrome,
      secondary to focal segmental glomerulosclerosis, had persistent nephrotic range
      proteinuria despite aggressive treatment with steroids and cyclophosphamide. His
      steroid-resistant nephrotic syndrome resolved rapidly when he was
      serendipituously started on ibuprofen for the treatment of pericarditis. His
      proteinuria remained low at about 0.5 g/day over the next two years of treatment
      with ibuprofen and without any increase in his serum creatinine. He did not
      receive any ACE inhibitor or calcium channel blocker. An attempt to discontinue
      ibuprofen resulted in the relapse of his nephrotic syndrome. Upon restarting
      ibuprofen, his proteinuria decreased to less than 0.5 g/day again. We conclude
      that ibuprofen has been effective and safe for the management of nephrotic
      syndrome in this patient. However, careful monitoring is prudent to assess the
      potential adverse effects of ibuprofen on renal function with prolonged use.

PMID- 9021246
TI  - Membranoproliferative glomerulonephritis secondary to tuberculosis.

PMID- 9021247
TI  - Urinary kallikrein excretion in early diabetic nephropathy.

PMID- 9021248
TI  - The effect of needle gauges on recirculation: a reply to Hasbargen et al.

PMID- 9021249
TI  - Possible mechanism of progressive renal failure in Crow-Fukase syndrome.

PMID- 9021250
TI  - Detection of TGF-beta 1 in CAPD effluents.

PMID- 9021251
TI  - Severe pancitopenia associated with antithyroid drugs in a patient with Graves'
      disease and chronic renal failure.

PMID- 9021252
TI  - Overview of motor neuron disease: classification and nomenclature.
AB  - Amyotrophic lateral sclerosis (ALS), although a disease that has been well
      recognized for nearly 150 years, still causes problems of diagnosis and
      management, as there is no definitive diagnostic test, and the disease is
      pleomorphic. Research criteria were developed for the categorization of definite,
      probable, and possible ALS at the El Escorial Workshop (published in 1994). The
      principal features are upper and lower motor neuron signs at several levels of
      the neuraxis, without involvement of other neurological systems. Separation of
      ALS or motor neuron disease (MND) from the spinal muscular atrophies or
      hereditary spastic paraplegia can be difficult. The relatively rapid progression
      to death in an average of 5 years is one of the hallmarks of ALS. However, some
      cases are relatively more benign. The recent finding that mutations of the SOD1
      gene underlie about 20% of familial cases of ALS has allowed the recognition that
      all phenotypes can occur in different members of the same family with the same
      mutation, clarifying earlier suggestions that different phenotypes represent
      different diseases. Until the cause and cure of ALS are found, neurologists and
      rehabilitation specialists must continue to provide essential support for
      patients with this devastating disease.

PMID- 9021253
TI  - Epidemiology of ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder
      of unknown etiology. ALS onset is rare before age 40 and increases with age
      thereafter. Men are at higher risk than women (ratio 1.3:1). Other than age and
      gender, the only indisputable risk factor for ALS is genetic susceptibility, with
      familial cases occurring in about 10% of most case series. Genetic linkage
      studies have provided evidence that a mutant form of the gene that codes for
      Cu/Zn superoxide dismutase, an endogenous free radical scavenger, is important in
      15-20% of familial cases. Epidemiologic studies have identified associations of
      sporadic ALS with work in occupations that involve toxicant exposure.
      Environmental toxicants may act against a background of increased genetic
      susceptibility; however, genetically acquired biochemical defects have not been
      identified in sporadic ALS patients. Other epidemiologic theories of disease
      etiology have emphasized the potential role of physical trauma, electrical shock,
      and vigorous physical exertion, but evidence regarding these factors is
      inconsistent.

PMID- 9021254
TI  - Comparison of pathological alterations in ALS and a murine transgenic model:
      pathogenetic implications.
AB  - The first part of this paper summarizes the main pathological features of
      sporadic amyotrophic lateral sclerosis (ALS) and familial amyotrophic lateral
      sclerosis (FALS). In both diseases, the primary lesion consists of degeneration
      of both upper and lower motor neurons, resulting in severe neuronal loss,
      particularly in the spinal cord. An important difference between sporadic ALS and
      FALS is in the involvement of sensory and spinocerebellar projections in the
      latter. The second part of the paper will compare the familial form of ALS with
      its recently described transgenic murine model. The production of this model
      followed the discovery that FALS is tightly linked to several different mutations
      in the enzyme Cu,Zn superoxide dismutase (SOD), a ubiquitous enzyme involved in
      the dismutation of superoxide anion to hydrogen peroxide. A human transgene with
      one of the identified mutations was expressed in mice, and the resulting progeny
      developed clinical and pathological changes that, in the late stages of disease,
      were very similar to those in patients with FALS. There was, in fact, exquisite
      degeneration of motor neurons in spinal cord and brain stem, as well as
      degeneration of white matter tracts of the spinal cord, of the anterior roots and
      neurogenic atrophy of skeletal muscles, as described in patients with FALS.
      Beckman and colleagues postulated that mutations in SOD may alter the structure
      of the copper active site with resultant decrease in superoxide anion dysmutation
      while favoring an increase in reactivity with other radicals such as
      peroxynitrite. The formation of nitronium-like intermediate could damage
      proteins, particularly by nitration of tyrosine residues. Nitration of tyrosine
      kinases and altered phosphorilation of neurofilaments could be particularly
      damaging for motor neurons.

PMID- 9021255
TI  - Familial amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is inherited in ten percent of cases as a
      Mendelien trait. Familial ALS (FALS) is genetically heterogeneous and transmitted
      either as an autosomal dominant (DFALS) or an autosomal recessive (RFALS) trait.
      Fifteen percent of DFALS families have mutations in the gene for Cu,Zn superoxide
      dismutase (SOD1) which is coded on chromosome 21. These mutations result in
      decreased SOD1 activity and shortened half-life of the protein in most instances.
      Several observations suggest that the degeneration of motor neurons in DFALS is
      caused by the gain of a novel toxic function by mutated SOD1 rather than by the
      decrease of SOD1 activity. Possible mechanisms of the novel neurotoxic function
      of mutated SOD1 are discussed. The role of eventual neurofilament involvement in
      the pathogenesis of ALS is also discussed. The locus for one form of RFALS has
      been mapped to chromosome 2q33. FALS can also be associated with dementia and the
      gene locus for one form of hereditary ALS-dementia syndrome maps to chromosome
      17q21-22.

PMID- 9021256
TI  - Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis.
AB  - The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is unknown, but
      several observations suggest that glutamate could participate in selective motor
      neuron degeneration. Extracellular levels of glutamate are elevated in ALS.
      Synaptic concentrations of glutamate are regulated by high-affinity glutamate
      transport, and defects in glutamate transport have also been observed in ALS
      tissue. Three sodium-dependent glutamate transporters have now been identified: a
      neuronal transporter EAAC1, and two astroglial transporters GLT-1 and GLAST. The
      defect in glutamate transport in ALS appears to be relatively specific for the
      GLT-1 subtype. The role of chronic excess glutamate and glutamate transporter
      loss has been investigated in experimental paradigms, where it was found that
      excitotoxicity could account for selective motor neuron degeneration. These
      culture paradigms have demonstrated that motor neurons are sensitive to glutamate
      toxicity via non-NMDA receptors and that various agents (e.g., antioxidants,
      glutamate release inhibitors, non-NMDA receptor antagonists) can be
      neuroprotective. These experimental studies will provide a basis for
      understanding the primary and secondary role of glutamate in motor neuron death
      and will provide important insight into possible therapeutic interventions.

PMID- 9021257
TI  - Amyotrophic lateral sclerosis and viruses.
AB  - Amyotrophic lateral sclerosis (ALS) is a disease of unknown etiology. A number of
      theories have been pursued to explain the cause of ALS, including viral
      infection. This review examines the evidence implicating viruses in the
      pathogenesis of ALS, as well as current studies of naturally occurring and
      experimental models of virus-induced motor neuron disease (MND). The association
      of viruses and ALS remains to be established. The study of animal models of virus
      induced MND may shed light on processes relevant to the etiology of ALS.

PMID- 9021258
TI  - Increased intracellular calcium triggered by immune mechanisms in amyotrophic
      lateral sclerosis.
AB  - Although the causes of motor neuron degeneration and death in amyotrophic lateral
      sclerosis (ALS) is unknown, recent evidence suggests a prominent role for
      increased intracellular calcium, possibly triggered by autoimmune mechanisms. The
      presence in ALS patients of paraproteinemias, lymphomas, lymphoid cells in the
      central nervous system (CNS) and the availability of animal models of immune
      mediated motor neuron disease provide circumstantial evidence for autoimmunity.
      Direct evidence derives from the demonstration that ALS IgGs bind to voltage
      gated calcium channels in 75% of sporadic cases, but not in familial ALS cases,
      and that ALS IgGs increase N-type and P-type calcium currents in neuronal cells
      and in lipid bilayers. These same ALS IgGs are cytotoxic for a motor neuron cell
      line (VSC 4.1) in vitro. In addition, following passive transfer to mice in vivo,
      ALS IgGs produce ultrastructural and calcium changes in synaptic vesicles and
      mitochondria of motor axon terminals, as well as in rough endoplasmic reticulum
      and Golgi complex of motor neuron perikarya, but not in sensory neurons or
      Purkinje cells. The reason for the selective vulnerability of motor neurons is
      not clearly defined, but a prominent possibility is the physiological absence in
      motor neurons of the calcium-binding proteins calbindin-D28k and parvalbumin.
      These studies emphasize the central role of increased intracellular calcium in
      motor neuron cell death in sporadic ALS, and the role of autoimmunity in
      triggering such increases.

PMID- 9021259
TI  - Animal models of ALS.
AB  - Animal models of amyotrophic lateral sclerosis (ALS) provide a unique opportunity
      to study this incurable and fatal human disease both clinically and
      pathologically. This is particularly true for certain pathological and
      therapeutic studies that are impractical or impossible to perform in human
      patients. Nonetheless, postmortem ALS tissue remains the "gold standard" against
      which pathologic findings in animal models must be compared. Four natural disease
      models have been most extensively studied, including three mouse models: motor
      neuron degeneration (Mnd), progressive motor neuronopathy (pmn), wobbler, and one
      canine model: hereditary canine spinal muscular atrophy (HCSMA). The wobbler
      mouse has been the most extensively studied of these models with analyses of
      clinical, pathological (perikaryon, axon, muscle), and biochemical features.
      Experimentally induced ALS animal models have allowed controlled testing of
      various neurotoxic, viral and immune-mediated mechanisms. Molecular techniques
      have recently generated mouse models in which genes relevant to the human disease
      or motor neuron biology have been manipulated. The most clinically relevant of
      these is a transgenic mouse overexpressing the mutated SOD1 gene of FALS
      patients, which has already provided significant insights into mechanisms of
      motor neuron degeneration in this disease. Because no single animal model
      perfectly reflects all the clinical and pathological characteristics of ALS,
      study of selected features from the most relevant models will contribute to a
      better understanding of the pathogenesis and/or etiology of this disease.

PMID- 9021260
TI  - Emerging directions in ALS therapeutics: palliative therapies at the advent of
      the twenty-first century.

PMID- 9021261
TI  - Kohonen map as a visualization tool for the analysis of protein sequences:
      multiple alignments, domains and segments of secondary structures.
AB  - The method of Kohonen maps, a special form of neural networks, was applied as a
      visualization tool for the analysis of protein sequence similarity. The procedure
      converts sequence (domains, aligned sequences, segments of secondary structure)
      into a characteristic signal matrix. This conversion depends on the property or
      replacement score vector selected by the user. Similar sequences have small
      distance in the signal space. The trained Kohonen network is functionally
      equivalent to an unsupervised non-linear cluster analyzer. Protein families, or
      aligned sequences, or segments of similar secondary structure, aggregate as
      clusters, and their proximity may be inspected on a color screen or on paper.
      Pull-down menus permit access to background information in the established text
      oriented way.

PMID- 9021262
TI  - A general algorithm to compute multilocus genotype frequencies under various
      mating systems.
AB  - This paper provides a general method to derive algebraic expressions of genotype
      frequencies for multiple loci under various mating systems, including random
      mating, back-crossing, selfing, and full-sib mating. For each mating system,
      general equations are presented. In the case of three loci, comprehensive tables
      provide recurrence equations for genotype frequencies under random or self
      mating, and expected genotype frequencies after two generations of full-sib
      mating. Our results should prove useful in genetic linkage analysis.

PMID- 9021263
TI  - MulBlast 1.0: a multiple alignment of BLAST output to boost protein sequence
      similarity analysis.
AB  - The protein sequence similarity search has become a major tool for biologists.
      Various efficient and rapid programs and comparison matrices have been designed
      and refined in order to perform the scanning task (BLAST, FASTA, Automat, etc.).
      However, the final step of the search, the analysis of the results, is still
      tedious and time consuming. In order to optimize true-positive hit screening, we
      have developed a program which makes a multiple alignment from the BLAST search
      output. Conserved sequence segments are pointed out. It makes the recognition of
      already known as well as new sequence patterns easier. It allows at a glance a
      rapid identification of significant similarities, protein family signature and
      new sequence motifs. This alignment is written in a compatible format for the GCG
      programs LineUp and ProfileMake.

PMID- 9021264
TI  - Bi-De: an application for simulating phylogenetic processes.
AB  - Birth-Death (Bi-De) is an application for the Apple Macintosh which simulates the
      growth of phylogenetic trees using various models of lineage birth and death. The
      trees produced are intended to be analogous to those reconstructed from molecular
      sequence data. The user may define a constant birth rate and death rate or a
      function describing how these rates vary by time or population size.
      Instantaneous mass extinctions can also be simulated. The package allows the tree
      produced to be used as a template for the simulated evolution of molecular
      sequence data under a range of different transition models.

PMID- 9021265
TI  - Parallel hardware for sequence comparison and alignment.
AB  - Sequence comparison, a vital research tool in computational biology, is based on
      a simple O(n2) algorithm that easily maps to a linear array of processors. This
      paper reviews and compares high-performance sequence analysis on general-purpose
      supercomputers and single-purpose reconfigurable, and programmable co-processors.
      The difficulty of comparing hardware from published performance figures is also
      noted.

PMID- 9021266
TI  - The effects of social structure, geographical structure, and population size on
      the evolution of mitochondrial DNA: I. A simulation model.
AB  - A program simulating the distribution of variation in mitochondrial DNA in
      macaques is described. Empirical studies of the rates of nucleotide substitution
      and geographical patterning of mtDNA variation in these and other monkey species
      have demonstrated striking differences from equivalent measures of nuclear DNA
      and called into question the assumptions informing the use of mtDNA to elucidate
      phylogenetic relationships in organisms with relatively complex social
      organization. The model presented here incorporates social-structural variables
      as well as geographical structure and population size in order to clarify the
      determinants of the pattern of mtDNA evolution in macaques. The program, SHINES
      (Simulation of Hereditary Innovations in Neutral Evolution of Simians), employs
      an economical procedure for representing the haplotypes of the animals in the
      simulated population.

PMID- 9021267
TI  - Rule-based system for the fast identification of species of Indian Anopheline
      mosquitoes.
AB  - In a developing country like India, classification and identification of the
      species of Anopheline mosquitoes in control operations of mosquito-borne diseases
      is of paramount importance. The WHO monograph, which describes the taxonomic data
      in the form of a pictorial key is generally difficult to understand by a non
      taxonomist. Utilizing the principles of ID3 algorithm, a novel rule-based system,
      for the fast identification of unknown species of Indian Anopheline mosquitoes,
      is developed. The rule-based system is user-friendly, menu-driven and even a
      novice can make use of it in the identification of the unknown species with
      little practice. The above software is available on floppy disk and can be
      obtained with a minimum cost. This program can be ported on 5 1/4" or 3 1/2"
      floppy disk.

PMID- 9021268
TI  - Methods for comparing a DNA sequence with a protein sequence.
AB  - We describe two methods for constructing an optimal global alignment of, and an
      optimal local alignment between, a DNA sequence and a protein sequence. The
      alignment model of the methods addresses the problems of frameshifts and introns
      in the DNA sequence. The methods require computer memory proportional to the
      sequence lengths, so they can rigorously process very huge sequences. The
      simplified versions of the methods were implemented as computer programs named
      NAP and LAP. The experimental results demonstrate that the programs are sensitive
      and powerful tools for finding genes by DNA-protein sequence homology.

PMID- 9021270
TI  - A polynomial-time algorithm for a class of protein threading problems.
AB  - This paper presents an algorithm for constructing an optimal alignment between a
      three-dimensional protein structure template and an amino acid sequence. A
      protein structure template is given as a sequence of amino acid residue positions
      in three-dimensional space, along with an array of physical properties attached
      to each position; these residue positions are sequentially grouped into a series
      of core secondary structures (central helices and beta sheets). In addition to
      match scores and gap penalties, as in a traditional sequence-sequence alignment
      problem, the quality of a structure-sequence alignment is also determined by
      interaction preferences among amino acids aligned with structure positions that
      are spatially close (we call these 'long-range interactions'). Although it is
      known that constructing such a structure-sequence alignment in the most general
      form is NP-hard, our algorithm runs in polynomial time when restricted to
      structures with a 'modest' number of long-range amino acid interactions. In the
      current work, long-range interactions are limited to interactions between amino
      acids from different core secondary structures. Dividing the series of core
      secondary structures into two subseries creates a cut set of long-range
      interactions. If we use N, M and C to represent the size of an amino acid
      sequence, the size of a structure template, and the maximum cut size of long
      range interactions, respectively, the algorithm finds an optimal structure
      sequence alignment in O(21C NM) time, a polynomial function of N and M when C =
      O(log(N + M)). When running on structure-sequence alignment problems without long
      range intersections, i.e. C = 0, the algorithm achieves the same asymptotic
      computational complexity of the Smith-Waterman sequence-sequence alignment
      algorithm.

PMID- 9021269
TI  - LALNVIEW: a graphical viewer for pairwise sequence alignments.
AB  - LALNVIEW is a graphical program for visualising local alignments between two
      sequences (protein or nucleic acids). Sequences are represented by coloured
      rectangles to give an overall picture of their similarities. LALNVIEW can display
      sequence features (exon, intron, active site, domain, propeptide, etc.) along
      with the alignment. When using LALNVIEW through our Web servers, sequence
      features are automatically extracted from database annotations (SWISS-PROT,
      GenBank, EMBL or HOVERGEN) and displayed with the alignment. LALNVIEW is a useful
      tool for analysing pairwise sequence alignments and for making the link between
      sequence homology and what is known about the structure or function of sequences.
      LALNVIEW executables for UNIX, Macintosh and PC computers are freely available
      from our server (http:// expasy.hcuge.ch/sprot/lalnview.html).

PMID- 9021272
TI  - The PDBFINDER database: a summary of PDB, DSSP and HSSP information with added
      value.
AB  - MOTIVATION: The Protein Data Bank currently contains more than 4700 protein
      coordinate sets. It is often desirable to make a selection from these files based
      on a criterion like R-factor, experimental method, length of the amino acid
      sequence, or the number of homologous sequences in SWISSPROT. Doing this using
      the distributed form of the Protein Data Bank can be a tedious task, because (1)
      this requires reading one file for every single entry, and (2) not all of the
      information is present in a consistent computer readable way in all of the
      entries. RESULTS: The PDBFINDER database provides an easy to interpret file
      containing summary information about all Protein Data Bank files. Summary
      information from the DSSP (Definition of Secondary Structure of Proteins) and
      HSSP (Homology derived Secondary Structure of Proteins) databases is also
      included. Furthermore, where essential data were missing from the Protein Data
      Bank file, this information has been retrieved from the original literature.
      AVAILABILITY: The latest version of the PDBFINDER database can be downloaded by
      anonymous ftp from swift.embl-heidelberg.de, directory:/pdbfinder. CONTACT: E
      mail address hooft@embl-heidelberg.de.

PMID- 9021271
TI  - Correspondence discriminant analysis: a multivariate method for comparing classes
      of protein and nucleic acid sequences.
AB  - This report describes two applications of a multivariate method for studying
      classes of nucleotide or protein sequences: correspondence discriminant analysis
      (CDA). The first example is the discrimination between Escherichia coli proteins
      according to their subcellular location (membrane, cytoplasm and periplasm). The
      high resolution of the method made it possible to predict the subcellular
      location of E.coli proteins for whom this information is not known. The second
      example is discrimination between the coding sequences of leading and lagging
      strands in four bacteria: Mycoplasma genitalium, Haemophilus influenzae, E.coli
      and Bacillus subtilis. The programs used for computing the analysis are
      integrated in a publicly available package that runs on MacOS 7.x or Windows 95
      operating systems (http:/(/)biomserv.univ-lyonl.fr/ADE-4.html). These programs
      are also accessible through our World Wide Web server (http:/(/)biomserv.univ
      lyonl.fr/Net Mul.html).

PMID- 9021273
TI  - Fast sinogram computation and the sinogram-based alignment of images.
AB  - A direct Fourier method (DFM) to compute sinograms is described. Since the DFM is
      much faster than the customary rotation and projection process, novel uses of
      sinograms can be devised. As an example and an exercise on the properties of
      sinograms, a fast sinogram-based method to align large sets of images is
      described. The method is based on shift-invariant functions to detect rotations,
      and on tomographic reconstructions of cross-correlation functions to detect
      relative shifts. It has been implemented in a novel library, SIGNAL, used to
      align images of macromolecular assemblies observed in the electron microscope. A
      comparative analysis of the complexity of sinogram- and imagebased methods, as
      well as quite a few tests with EM images, show that SIGNAL runs faster, the
      accuracy being the same.

PMID- 9021274
TI  - A simple method for the removal of mains interference from pre-recorded
      electrophysiological data.
AB  - MOTIVATION: A common problem with electrophysiological recording is the
      contamination of the signal of interest with interference generated at mains
      frequency. Standard filtering techniques are often inappropriate because the
      signal of interest has components spectrally close to the mains frequency.
      RESULTS: A digital subtraction method is described for removing mains frequency
      interference from pre-recorded data. The data are first digitized with a sample
      rate that is some direct multiple of mains frequency. Next a 20 ms (for UK mains
      frequency) data set is constructed containing the average interference pattern.
      This is subtracted from each 20 ms window of the raw data. Finally, the mean
      value of the interference is added back to the raw data to restore the DC
      component. AVAILABILITY: A Windows program which implements the method for the
      EGAA data acquisition system (R.C.Electronics, Santa Barbara, CA) is available
      from the author. CONTACT: wjh@st-andrews.ac.uk

PMID- 9021275
TI  - SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular
      phylogeny.
AB  - SEAVIEW and PHYLO_WIN are two graphic tools for X Windows-Unix computers
      dedicated to sequence alignment and molecular phylogenetics. SEAVIEW is a
      sequence alignment editor allowing manual or automatic alignment through an
      interface with CLUSTALW program. Alignment of large sequences with extensive
      length differences is made easier by a dot-plot-based routine. The PHYLO_WIN
      program allows phylogenetic tree building according to most usual methods
      (neighbor joining with numerous distance estimates, maximum parsimony, maximum
      likelihood), and a bootstrap analysis with any of them. Reconstructed trees can
      be drawn, edited, printed, stored, evaluated according to numerous criteria.
      Taxonomic species groups and sets of conserved regions can be defined by mouse
      and stored into sequence files, thus avoiding multiple data files. Both tools are
      entirely mouse driven. On-line help makes them easy to use. They are freely
      available by anonymous ftp at biom3.univ-lyon1.fr/pub/ mol_phylogeny or
      http:@acnuc.univ-lyon1.fr/, or by e-mail to galtier@biomserv.univ-lyon1.fr.

PMID- 9021276
TI  - Image and volume data rotation with 1- and 3-pass algorithms.
AB  - Three different implementations of the 3-pass algorithm of image and volume data
      rotation are illustrated and discussed. The three protocols use interpolation in
      real domain, with a peculiar implementation of the Shannon reconstruction, or
      phase shifts in Fourier domain. Accuracy and speed of the three methods are
      compared with corresponding values obtained with a 1-pass method. The results
      indicate that for low or moderate accuracy, 1-pass is more convenient than 3-pass
      rotation for both accuracy and speed. Very accurate rotations can be obtained in
      reasonable time if all steps of 3-pass rotation are performed in the Fourier
      domain.

PMID- 9021277
TI  - Selection of amino acid parameters for Fourier transform-based analysis of
      proteins.
AB  - Fourier analysis of the parametric profile of a sequence for the detection and
      localization of the structural motifs that are characteristic for biologically
      related proteins has been proposed. In order to select parameters that are most
      appropriate for this analysis, the informational capacity of 226 physicochemical,
      thermodynamic, structural and statistical amino acid parameters was analyzed.
      Based on the results, obtained for the four functionally unrelated protein model
      groups (lysozyme c, HIV-1 gp120, tubulin and tau proteins, and steroid hormone
      receptors), the electron-ion interaction potential has been selected as the
      unique amino acid property that can be used in Fourier transform-based analysis
      of proteins, independently of their biological function.

PMID- 9021278
TI  - The role of leisure in stroke rehabilitation.
AB  - Stroke patients often fail to resume full lives, even if they make a good
      physical recovery, and social and leisure pursuits show a particular decline. The
      usual goals of rehabilitation are mobility and independence in self-care, but
      recovery in a broader sense may be impeded if health professionals concentrate
      exclusively on these. Leisure has been shown to be closely associated with life
      satisfaction and would be a worthwhile, and now measurable, goal of
      rehabilitation. Elderly people show a decline in leisure activity which has been
      studied extensively and may provide a useful model for the more rapid decline
      seen in stroke patients. Further research is needed to confirm the finding that
      specialized occupational therapy can be effective in raising leisure activity,
      and to show whether this will translate into improved psychological well-being.

PMID- 9021279
TI  - Coping with chronic neurological impairment: a contrastive analysis of
      Parkinson's disease and stroke.
AB  - This study aimed at a contrastive analysis of coping strategies and psychosocial
      alterations in patients with Parkinson's disease (PD) and stroke (CVA) and their
      relatives. Fifty-four PD and 50 CVA patients were investigated with a
      standardized semistructured interview to assess the severity of psychosocial
      changes following illness, the Freiburg Questionnaire on Coping with Illness, the
      Cornell Depression Scale and instruments to assess motor impairment. Psychosocial
      alterations were most prominent in the professional and emotional-cognitive
      domains. Degree of depression correlated with familial and emotional-cognitive
      alterations in both patient groups. Active problem-oriented coping and
      distraction predominated as coping styles. Religious relief and quest for sense
      were significantly more important for the PD patients. Coping styles did not
      correlate with degrees of depression, motor impairment or psychosocial
      alterations.

PMID- 9021280
TI  - Assessments of disability in women with rheumatoid arthritis in relation to grip
      force and pain.
AB  - The aim of this study was to assess disability with the Health Assessment
      Questionnaire (HAQ) and to evaluate the relationships between grip force, pain
      and difficulty in daily activities. Twenty women with rheumatoid arthritis were
      assessed with measurements of grip force and pain before and after grip test.
      Both the original HAQ version and an alternative rating model, not taking the use
      of assistive devices into account, were used. All patients reported pain which
      significantly increased after grip test and with a significant inverse
      correlation to grip force. All patients had assistive devices, on average 15
      devices (range 1-27). Ninety-one per cent of the patient's devices were in
      continued use, most frequently in the categories; Eating, Grip and Hygiene.
      Disability was significantly correlated to pain, grip force and use of assistive
      devices. When using the alternative ratings of 20 questions in HAQ, 8 of the 20
      questions showed significantly (p = 0.0003-0.0339) lower scoring, and the number
      of questions with significant correlations between grip force and disability
      increasing from 9 (r = 0.48-0.74, p = 0.039-0.001) to 14 questions (r = 0.47
      0.74, p = 0.047-0.001). Difference between intrinsic disability (without
      assistive devices) and actual disability (with such assistance) is not reflected
      in original HAQ. The present study indicates that assessment of actual disability
      by the alternative rating model is more often correlated to impairment (grip
      force) than disability assessed by original HAQ and can be considered to give a
      better assessment of actual disability than the original HAQ model.

PMID- 9021281
TI  - The short-term impact of Botox injections on speech disability in adductor
      spasmodic dysphonia.
AB  - This study investigates the impact of Botox injections on speech disability in a
      group of patients with adductor spasmodic dysphonia. Patient-perceived disability
      was assessed on the Speech Disability Questionnaire. A factor analysis on speech
      disability yielded five factors. Four of these, social isolation (p < 0.001),
      negative communication (p < 0.005), public avoidance (p < 0.05) and limited
      understanding (p < 0.01), showed significant change from prior to and one week
      post injection. Speech and language therapists' assessment also showed changes in
      voice quality over the same period. These findings are discussed in terms of the
      relationship between voice quality, disability and handicap, in adductor
      spasmodic dysphonia.

PMID- 9021282
TI  - Wheelchair users' experience of non-adapted and adapted clothes during sailing,
      quad rugby or wheel-walking.
AB  - The purpose of the present quasi-experimental post-test-design study was to
      compare 32 wheelchair users' (mostly para/tetraplegics) experience of wearing
      specially adapted clothes and non-adapted clothes for sailing, quad rugby or
      wheel-walking. Four existing assessment instruments were used: the Klein-Bell
      Activities of Daily Living Scale; a two-part Basic Information Questionnaire
      eliciting experience of effort, comfort and feeling of physical condition; the
      Experience Sampling Form for investigating the individuals' attitudes in terms of
      involvement and affective and activity mood states, and the Occupational Therapy
      Assessment of Leisure Time interview framework for collecting data about
      experience of leisure time. The wheelchair users all associated significantly
      greater comfort with use of the adapted clothes and, particularly the 'sailors',
      better physical condition. Overall, significantly greater involvement and more
      positive affect states were associated with the adapted clothes than with
      conventional garments, and mood state changed for the better. The wheelchair
      users set a higher priority upon work or leisure activities than upon
      independence in activities of daily living, and for this reason the Klein-Bell
      ratings showed great variation between the 'sailors' and the 'quad rugby players'
      (range 57%-93%), though these groups demonstrated more independence than the
      'wheel-walkers'. The results of the study confirm the value of adapting
      sportswear for handicapped people. Such adaptations should also be of benefit for
      other activities than those studied.

PMID- 9021283
TI  - Do it yourself: home-made aids for disabled elderly people.
AB  - We contacted the caregivers of patients admitted on a hospital respite care
      scheme and asked them about home-made or modified aids and appliances. Seven home
      made devices were discovered and inspected. They were an electric hoist, a
      builder's plastic skip used as a bath, a wheelchair support and tray made out of
      chipboard, stair rails made from old steel pipe, an improvised commode and a
      modified standard commode enabling the user to be cleaned in the sitting
      position. Several gadgets were innovative; others were dangerous. Two caregivers
      had injured themselves using the improvised aids. Others were at risk of injury.
      With an increasing tendency for Community Agencies to charge for equipment, more
      caregivers may design and build their own aids-some of which may be hazardous.
      Health professionals who visit elderly people at home should look for home-made
      gadgets with a view to promoting safety and discovering innovations which may
      help others.

PMID- 9021306
TI  - Epidemiologic methods in immunization programs.

PMID- 9021307
TI  - Epidemiologic aspects of human cryptosporidiosis and the role of waterborne
      transmission.

PMID- 9021308
TI  - Transmission of hepatitis C virus: rates, routes, and cofactors.

PMID- 9021310
TI  - Review of the evidence on fetal and early childhood antecedents of adult chronic
      disease.

PMID- 9021309
TI  - Mother-to-child transmission of human immunodeficiency virus type 1.
AB  - A great deal of progress has been made in our understanding of mother-to-child
      transmission of HIV-1. Standardization of case definitions and transmission rate
      calculation methodologies, and a broader array of diagnostic options for
      detection of infant HIV-1 infection, will enhance our ability to evaluate and
      compare cohorts worldwide. In the next decade, several intervention studies
      should be completed. Carefully designed intervention studies have the potential
      both to determine which interventions are effective as well as to add to our
      understanding of vertical transmission of HIV-1. Regional differences in vertical
      transmission rates reflect a variety of viral, host, and obstetric factors.
      Intervention strategies will probably need to be regionally designed, taking into
      consideration these factors. Further research on timing and correlates of
      vertical transmission is necessary to determine the extent to which specific
      clinical trials can be extrapolated to public health policy.

PMID- 9021311
TI  - Epidemiology of myopia.

PMID- 9021312
TI  - Cotinine as a biomarker of environmental tobacco smoke exposure.

PMID- 9021313
TI  - Nonsteroidal antiinflammatory drugs and colorectal cancer.

PMID- 9021314
TI  - Occupational risk factors for gastric cancer: an overview.

PMID- 9021315
TI  - Developmental dental defects associated with long breast feeding.
AB  - Despite its unequivocal advantages, breast feeding may be associated with
      undesired side-effects. Recently, we have shown an association between exposure
      via mother's milk to dioxins and developmental defects of the child's teeth. The
      present study was undertaken to analyze further the association between the
      duration of breast feeding and the occurrence of dental defects. For this
      purpose, 2 different populations were selected. The first population comprised 40
      children who had mineralization defects in the permanent 1st molars, and their
      age-living area- and sex-matched controls. The median duration of breast feeding
      was 9 months in the affected children compared to 6 months in the controls. The
      defects were more extensive after prolonged breast feeding. The second population
      consisted of 97 children whose mothers had been encouraged to extensive and
      prolonged breast feeding. Of these children, 24 had mineralization defects. They
      all had been breastfed longer than 8 months. In both study populations
      mineralization defects were associated with the duration of breast feeding. The
      result suggests that long breast feeding may increase the risk of mineralization
      defects in healthy children, possibly because of environmental contaminants that
      interfere with tooth development.

PMID- 9021316
TI  - Influence of dose and cessation of kiraiku, cigarettes and alcohol use on the
      risk of developing oral leukoplakia.
AB  - Data from a previously-reported study of oral leukoplakia-associated risk factors
      in a Kenyan population were further analyzed to determine the influence of dose
      and cessation. Specifically, risk analysis was made with respect to kiraiku (a
      traditional Kenyan type of home-made, hand-rolled tobacco product), cigarettes,
      and commercial beer. The relative risk (RR) of oral leukoplakia among those who
      smoked > 10 cigarettes was 14.7, as compared to 6.7 among those who smoked < or =
      10 cigarettes. With regard to duration, the RR increased from 7.4 in those who
      had smoked for < or = 15 years to 10.8 in those who had smoked for > or = 30
      years. Among those who had quit smoking, RR value was significant only in ex
      kiraiku smokers (RR = 4.9, 95% confidence interval (CI) = 2.3-20.4) and was
      dependent on both the duration of smoking and duration since quitting. For
      commercial beer, the RR was significant in consumers of > 10 bottles per drinking
      day (RR = 4.2, 95% CI = 1.0-3.9) and in those whose who drank for > or = 5 days
      per month (RR = 3.8, 95% CI = 1.0-15.1). Duration of beer consumption did not
      significantly influence the RR of oral leukoplakia. The RR in ex-beer consumers
      was not statistically significant. These findings suggest a dose-dependent
      association between oral leukoplakia and the use of tobacco and alcohol, in which
      the number of cigarettes smoked, the quantity of beer consumed, and the frequency
      of consumption were more important than the duration of use of these products.
      Furthermore, while oral leukoplakia due to cigarette smoking may regress
      completely, those due to kiraiku may persist for more than 10 years after
      cessation of these habits.

PMID- 9021317
TI  - Hypothetical mortality risk associated with spiral computed tomography of the
      maxilla and mandible.
AB  - In the present study, dose measurements have been conducted following examination
      of the maxilla and mandible with spiral computed tomography (CT). The
      measurements were carried out with 2 phantoms, a head and neck phantom and a full
      body phantom. The analysis of applied thermoluminescent dosimeters yielded
      radiation doses for organs and tissues in the head and neck region between 0.6
      and 16.7 mGy when 40 axial slices and 120 kV/165 mAs were used as exposure
      parameters. The effective dose was calculated as 0.58 and 0.48 mSv in the maxilla
      and mandible, respectively. Tested methods for dose reduction showed a
      significant decrease of radiation dose from 40 to 65%. Based on these results,
      the mortality risk was estimated according to calculation models recommended by
      the Committee on the Biological Effects of Ionizing Radiations and by the
      International Commission on Radiological Protection. Both models resulted in
      similar values. The mortality risk ranges from 46.2 x 10.6 for 20-year-old men to
      11.2 x 10(-6) for 65-year-old women. Using 2 methods of dose reduction, the
      mortality risk decreased by approximately 50 to 60% to 19.1 x 10(-6) for 20-year
      old men and 5.5 x 10(-6) for 65-year-old women. It can be concluded that a CT
      scan of the maxillofacial complex causes a considerable radiation dose when
      compared with conventional radiographic examinations. Therefore, a careful
      indication for this imaging technique and dose reduction methods should be
      considered in daily practice.

PMID- 9021318
TI  - Coordinated electromyographic activity of the human masseter and temporalis
      anterior muscles during mastication.
AB  - The present report aimed at evaluating the within- and between-subject
      electromyographic coordination between the masseter (M) and temporalis anterior
      (T) muscles during the performance of a standardized chewing task.
      Electromyographic activity of M and T muscles was recorded in 60 young healthy
      adults (30 men, 30 women) during two 15-s unilateral mastications of gum. Left
      right differential potentials (delta M = MR-ML, delta T = TR-TL) were computed
      and the square root of (delta M2 + delta T2) moduli were calculated. The maximum
      modulus relative to each masticatory cycle was located, and each modulus and
      differential potential were expressed as a % of the maximum modulus for each
      subject and chewing trial. For each subject and chewing side, the masticatory
      frequency was computed, and statistics of the moduli as %s of the maximum were
      determined by means of bivariate analysis. Within-subject repeatability of the
      unilateral chewing patterns was good. Mean population values for the modulus
      position (bivariate analysis), chewing frequency, and maximum modulus of the
      differential potentials (univariate statistics) were computed. A significant
      gender difference was found for the masticatory frequency, with larger values in
      men than in women. Conversely, no gender or side differences were found for the
      mean values of the maximum modulus or for the mean position of the percentage
      moduli. The chewing test applied allowed the evaluation of the neuromuscular
      coordination during the performance of a standardized physiologic activity. In
      particular, it quantified the within-subject and chewing side repeatability of
      the muscular pattern.

PMID- 9021319
TI  - Increased caries prevalence in 2.5-year-old children with cleft lip and/or
      palate.
AB  - The prevalence of dental caries was determined clinically in 2.5-year-old Dutch
      cleft lip and/or palate children (n = 76) and in children without congenital
      malformation (n = 75). The parents were given a structured questionnaire
      regarding the child's dietary habits, oral hygiene, fluoride exposure and social
      economic background. The prevalence of dental caries was higher in children with
      oral cleft than in children without oral cleft. Initial caries (white spots) was
      diagnosed in 17.1% of the subjects with oral cleft compared with 4.0% of the
      control subjects. Manifest caries (cavities) was found in 26.3% of the children
      with oral cleft compared with 5.3% of the controls. The dft score (manifest
      caries) was significantly higher for the oral cleft group (0.59 +/- 1.35) than
      for the control group (0.11 +/- 0.54). 52% of the total number of initial and
      manifest lesions were localized to the maxillary incisors. A multivariate
      analysis yielded initial caries, oral hygiene and treatment with preoperative
      infant orthopaedics as the variables significantly associated with manifest
      caries.

PMID- 9021320
TI  - Prediction of caries in pre-school children in relation to fluoride exposure.
AB  - The levels of salivary mutans streptococci and caries experience were used as
      predictors for caries incidence in 3 groups of pre-school children from areas
      with different levels of natural and topical fluoride exposure. Altogether 1022
      children, 4-5 years of age at baseline, were examined according to the WHO
      criteria and followed for 2 years. The low fluoride group (n = 374) had a low
      fluoride level in the piped water and no topical fluoride applications; the F
      varnish group (n = 442) had low water fluoride but semiannual topical
      applications of a fluoride varnish; the optimal fluoride group (n = 206) had an
      optimal level of fluoride in the drinking water and semiannual F-varnish
      applications. The number of salivary mutans streptococci was estimated and scored
      at baseline with the Strip mutans chair-side method. The sampling procedure was
      repeated in 337 children of the low fluoride group 3 weeks after baseline. In
      comparison with the low fluoride group, caries incidence was 30% and 60% lower in
      the F-varnish and the optimal fluoride group respectively. The caries predictive
      ability decreased with increasing fluoride exposure. The sum of sensitivity and
      specificity decreased from 151% (65% + 86%) in the low fluoride group to 131%
      (40% + 91%) in the optimal fluoride group. The positive predictive value was
      highest (62%) in the low fluoride group. Repeated salivary samplings at baseline
      did not improve the caries predictive power. The results suggest that the overall
      fluoride exposure should be taken into account when caries risk assessment
      strategies for preschool children are developed and implemented.

PMID- 9021321
TI  - Antiplaque, antibacterial, and anti-inflammatory properties of triclosan
      mouthrinses in combination with zinc citrate or polyvinylmethylether maleic acid
      (PVM-MA) copolymer.
AB  - The antibacterial agent triclosan has demonstrated antiplaque and antigingivitis
      activity in several clinical studies. Retention of antiplaque agents is of
      significance for their clinical effect. Triclosan has a relatively rapid
      clearance from the oral cavity, and attempts have been made to increase its oral
      retention. In the present clinical antiplaque study, it was found that 0.5%
      copolymer polyvinyl-methylether maleic acid (PVM-MA) or 0.5% zinc citrate, which
      are both added to commercial products, inhibited plaque formation to a similar
      degree when used in combination with 0.3% triclosan, 1.5% sodium lauryl sulfate
      (SL.S) and diluted propylene glycol (PG) in water (1:8). Plaque inhibition was
      significantly improved compared to a placebo solution. It was shown that these
      results could not be explained by an increase in antibacterial activity or by a
      change in the critical micellar concentration. The effect of the same solutions
      on SLS-induced inflammation on skin was also tested. It was seen that the
      triclosan/ zinc citrate solution and the control (triclosan/ethanol) decreased
      the inflammatory response, whereas the solutions containing triclosan in either
      propylene glycol (PG) or copolymer/PG did not exhibit any anti-inflammatory
      capacity.

PMID- 9021322
TI  - Acid anion profiles in dental plaque following consumption of cereal-based foods
      and fruits.
AB  - The aim of this study was to investigate the acid anions produced in plaque after
      chewing various cereal-based foods and fruits for one minute. Test foods were
      oranges, apples, bananas, Cornflakes, Branflakes, Weetabix, Alpen, white bread,
      wholemeal bread, rice and spaghetti, plus positive and negative controls of 10%
      sucrose and 10% sorbitol. 4 males and 3 females, aged 22-37 years, participated
      in the study .7 min from the start of chewing, 48-h plaque was collected from all
      accessible smooth surfaces, with no attempt to collect interproximal plaque, and
      centrifuged. Plaque fluid was withdrawn and analyzed by isotachophoresis for
      formate, succinate, lactate, acetate and propionate. At rest, acetate was the
      major anion present in plaque fluid, whereas following carbohydrate consumption,
      highest levels of lactate were detected followed by acetate. The amount of
      lactate only, detected in plaque fluid, was significantly correlated to the
      carbohydrate present in the food. It was concluded that important information
      regarding the acidogenicity of test foods is gained by studying the acid anion
      profile of plaque fluid.

PMID- 9021323
TI  - Electrophoresis of whole-cell soluble proteins of microorganisms isolated from
      bacteremias in endodontic therapy.
AB  - We have previously demonstrated that anaerobic bacteria are the microorganisms
      most frequently isolated from blood following endodontic therapy of teeth with
      apical periodontitis. Phenotypic characterisation of the isolates suggested that
      the bacteria in the blood originated from the root canal. The present experiment
      using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was
      carried out in an effort to verify these findings, and to further study the
      microorganisms involved in endodontic bacteremias. Soluble cellular proteins were
      extracted from 11 reference strains and 26 bacterial isolates recovered from the
      root canal and blood. These included Propionibacterium acnes, Peptostreptococcus
      prevotii, Fusobacterium nucleatum, Prevotella intermedia. Actinomyces israelii,
      Streptococcus intermedius, Streptococcus sanguis. The electrophoretic patterns
      mostly confirmed the identity of the isolates as determined by the biochemical
      and antimicrobial resistance tests. Furthermore, with this typing method the
      species Prevotella intermedia and Prevotella nigrescens could be differentiated.
      These species had been recovered from both root canal and blood. Also,
      differences between subspecies of Fusobacterium nucleatum became evident with SDS
      PAGE, and the results indicated that the organism recovered from the root canal
      and blood was Fusobacterium nucleatum subsp. vincentii. The electrophoretic
      patterns of the different organisms isolated from the root canal and the blood
      were similar, providing further evidence that the bacteria found in the blood
      originated from the root canal.

PMID- 9021324
TI  - Apoptosis in human and rat dental pulp.
AB  - Apoptotic cells were visualized in human premolar and rat molar pulps using
      either the TUNEL method, which stains DNA strand breaks by in situ nick end
      labeling, or labeling sections with an anti-transglutaminase antibody. Apoptotic
      cells were evident at the periphery of the pulp, mostly in a sub-odontoblastic
      location, and were more numerous in the crown than in the root region of the
      pulp. Most odontoblasts were unlabeled. A few apoptotic nuclei in the pulp of rat
      molars displayed the characteristics of chromatin condensation, as observed by
      electron microscopy. Many cell debris resembling apoptotic bodies were also
      observed. The 3 methods support the occurrence of apoptosis in the dental pulp.
      As this phenomenon was observed in healthy teeth apoptosis is probably involved
      in the regulation of the pulp cell population.

PMID- 9021325
TI  - Effect of cortical perforations of both graft and host bed on onlay incorporation
      to the rat skull.
AB  - The mechanisms involved in the integration of autogeneic bone grafts still
      attract much interest due to their clinical importance. The purpose of this study
      was to obtain data on the effects of a combination of cortical bone perforations
      both at the recipient site and the inner layer of a bicortical graft. 12 adult
      rats obtained femoral or tibial bicortical bone grafts from isogeneic donors to
      the tibia, one on each leg. On the experimental side, both the recipient bed and
      the inner cortical graft layer received multiple perforations (0.25 mm in
      diameter), while on the control side, only perforations of the recipient cortical
      bed were made. The findings were assessed by routine histology and
      immunohistochemical analysis for some bone and cartilage matrix proteins after 4
      and 20 weeks. The combined cortical perforations of the graft and the host bed
      induced a locally improved bony incorporation of the graft and a corticalization
      of the graft marrow, implying improved mechanical stability. The graft height
      persistence was similar between groups. Intense labelling of the bone matrix
      proteins was apparent in all bone tissue and by diversified intensity at its
      various components, demonstrating ongoing remodeling activities. PRELP and
      fibromodulin mainly outlined the soft tissues surrounding the graft and compact
      bone sealing off the graft marrow. Immunolabelling contributed a more delicate
      picture of the mechanisms involved in graft incorporation.

PMID- 9021326
TI  - Matrix metalloproteinases-1 and -8 and TIMP-1 mRNA levels in normal and diseased
      human gingivae.
AB  - Interstitial collagenases, including matrix metalloproteinase-1 (MMP-1) and -8
      (MMP-8), serve as initiators of extracellular matrix destruction in periodontal
      disease. Collagenase activities are mainly regulated by tissue inhibitors of
      metalloproteinases (TIMPs). We tested the effects of inflammation on MMP-1 and
      MMP-8 gene expression in periodontal disease. To determine the relative abundance
      of these mRNAs in gingiva, we used a reverse transcription-polymerase chain
      reaction (RT-PCR) assay. Gingival biopsies were divided into 2 groups; a control
      group and an inflamed group with severe gingivitis or periodontitis. The MMP-1
      mRNA levels were significantly elevated in inflamed gingiva, while the levels of
      the MMP-8 transcript were not different in the 2 groups and barely detectable by
      RT-PCR assay. The expression of the TIMP-1 gene was not altered, and remained
      higher than any of these other genes in both control and diseased gingivae. These
      results suggest that MMP-1 rather than MMP-8 may play an important role in the
      initiation of collagen degradation in periodontal disease. However, the
      possibility remains that MMP-8 plays an important role in periodontal tissue
      destruction, since the mRNA abundance and not the enzyme activity was assessed.

PMID- 9021327
TI  - Facilitated diffusion by iontophoresis of vasoactive agents to the rat incisor
      pulp.
AB  - The use of iontophoresis for facilitated diffusion of vasoactive agents into the
      dental pulp was investigated in lower incisor teeth of anaesthetized rats.
      Acetylcholine, carbachol and noradrenaline were iontophoresed with anodal and
      sodium nitroprusside with cathodal direct current through a superficial dentin
      exposure. Pulpal blood flow was measured with laser Doppler flowmetry. Current
      intensities below 100 microA of both polarities, using sodium chloride as a
      medium, caused no or minor afferent nerve-induced vasodilation, but excited
      sympathetic fibres of the pulp in a current-dependent manner. The current
      threshold for facilitated diffusion of acetylcholine was about 20 microA. The
      vascular responses to the cholinergic and noradrenergic drugs appeared within a
      minute after the onset of current and they were abolished by systemic
      administration of atropine and phenoxy benzamine, respectively. Iontophoresis of
      acetylcholine (40-100 microA for 20-120 s) caused a 3-fold increase of pulpal
      blood flow which was not dose-dependent; carbachol provoked a high-magnitude,
      long-lasting vasodilation and so did sodium nitroprusside. Noradrenaline caused a
      long-lasting vasoconstriction. In denervated rats iontophoresis of carbachol had
      effects similar to those seen in intact animals. None of the drugs used locally
      had any effect on systemic blood pressure. The results of this study indicate
      that iontophoresis can be used for delivery of vasoactive agents from an exposed
      dentin surface into the pulp in sufficient quantity to elicit drug-specific local
      vascular responses without causing systemic vascular effects.

PMID- 9021328
TI  - The blocking effect of iontophoretic administration of lidocaine on neurogenic
      vascular reactions in rat dental pulp.
AB  - The blocking effect of lidocaine on nerve-induced vascular reactions was
      investigated in lower incisor teeth of anaesthetized rats. Pulpal blood flow was
      measured with laser Doppler flowmetry. Monopolar electrical stimulation of the
      rat incisor evoked a biphasic vascular response: an initial vasoconstriction was
      followed by a long-lasting vasodilation. Iontophoresis of lidocaine on a
      superficially exposed dentin surface with 60 microA of anodal direct current for
      20 min blocked almost completely the stimulus-induced blood flow increase for
      about 25 min without any systemic effects. Iontophoresis of lidocaine with 40
      microA for 20 min was almost without effect. Topical application of a mixture of
      lidocaine and prilocaine (25 + 25 mg/ml) in deep dentinal cavities was also
      without effect on the neurogenic reactions. Intravenous administration of
      lidocaine at 5 and 10 mg/kg in rats pretreated with phenoxybenzamine reduced the
      stimulus-induced increase in blood flow by an average of 29% and 54%,
      respectively, whereas the remaining alpha-adrenoceptor resistant vasoconstriction
      was not influenced. The present results show that iontophoresis of lidocaine on
      exposed dentin blocks nerve-induced vascular responses without causing systemic
      effects.

PMID- 9021329
TI  - Prevention of etretinate-induced craniofacial malformations by vitamin B6 in the
      rat.
AB  - The preventive effect of vitamin B6 on etretinate-induced malformations in
      pregnant Sprague-Dawley rats was studied. The etretinate-induced malformation was
      produced by intraperitoneal administration of 10 mg/kg etretinate at embryonal
      day 8.5. Vitamin B6 was administered as intramuscular injections at embryonal day
      7.5 and 8.5. Vitamin B6 reduced the number and severity of facial clefts,
      micrognatia, meningocele, microtia and blood vessel anomalies. It is suggested
      that vitamin B6 induces suppressive effects on etretinate-induced teratogenesis
      when administered before or at the same time as the teratogen.

PMID- 9021330
TI  - Microanatomy of the moose temporomandibular joint (Alces alces; Linnaeus, 1758).
AB  - Temporomandibular joint (TMJ) histology was investigated in 8 female Scandinavian
      moose. 5 were 1-year-old with a carcass weight (cw) of 125-140 kg, and 3 were 2
      years-old (160-175 kg cw). The condylar articular surface consisted of a
      connective tissue lining with parallel collagen fibres. Numerous blood vessels
      were observed adjacent to the joint chamber. Below the fibrous layer, a
      proliferative cellular zone of undifferentiated mesenchymal cells was situated.
      These cells differentiated into chondroblasts and hypertrophied chondrocytes.
      Further down, an endochondral ossification process was initiated. Vertically
      directed invaginations were observed. A similar cellular organization was
      identified in the temporal component. However, the undifferentiated mesenchymal
      cell layer was discontinuous. The disc showed dense collagen bundles without main
      alignment. Vessels were identified throughout the entire disc. The results
      indicate that the cellular organization of the moose TMJ is similar to the TMJ
      histology found in other mammals but differences do occur.

PMID- 9021331
TI  - Bonding of resin cements to a metal substrate: influence of pretreatment on the
      adherence energy.
AB  - The adherence of resin cements to restoration as well as tooth structure is of
      prime importance for the longevity of cemented restorations. It was the aim of
      the study to investigate the effect of an acid and a base primer on (i) surface
      polarity of a nonprecious alloy and on (ii) adherence energy of resin cements
      bonded to the alloy. The beams were pretreated with a 3% acetone solution of
      either maleic acid or N,N-diethanol-p-toluidine, and the solvent evaporated. The
      polarity was determined by means of measurements of contact angles. The adherence
      energy was measured by means of the wedge test, according to which 2 beams were
      glued together with the resin cement. A wedge was introduced between the joined
      beams to create a fissure, and on the basis of the length of the fissure, the
      adherence energy was calculated. It was found that the polar component of the
      surface free energy of the alloy increased as a consequence of the pretreatments.
      The results also showed that the pretreatments gave rise to an increase in
      adherence energy of 11-15 J/m2, equivalent to relative increases of 22-54%. The
      observed increases in adherence energy may be due to an increase in polar
      interactions at the interface between adhesive and substrate.

PMID- 9021332
TI  - Effect of surface coatings on flexural properties of glass ionomers.
AB  - The purpose of this study was to investigate the change in flexural strength and
      fracture toughness of light-cured glass ionomer cements after long-term immersion
      in water, and to investigate the effect of surface coatings on their properties.
      2 resin-modified and 1 conventional glass ionomer cements were employed. For the
      flexural strength, a 25 x 2 x 2 mm stainless steel mold was used. For the
      fracture toughness (KtC), single edge notch specimens with dimensions 25 x 2.5 x
      5 mm and a 0.5 mm notch (a/W = 0.5) were prepared in a stainless steel mold.
      Specimens were subjected to the 3 point bending at 0.5 mm/min after storage in 37
      degrees C water for the periods of 1 h, 24 h, 1 wk, 1 month, and 6 months. The
      glass ionomer cements tended to exhibit an increase in mechanical properties over
      the 24-h period and then to maintain a constant strength. The surface protection
      of the resin-modified glass ionomer cement has some effect on the mechanical
      properties during early setting reactions, and it is desirable that the cement
      should be protected from direct water contact for at least 1 h after cement
      mixing.

PMID- 9021333
TI  - Carbon fiber reinforced root canal posts. Mechanical and cytotoxic properties.
AB  - The aim of this study was to compare the mechanical properties of a prefabricated
      root canal post made of carbon fiber reinforced composites (CFRC) with metal
      posts and to assess the cytotoxic effects elicited. Flexural modulus and ultimate
      flexural strength was determined by 3 point loading after CRFC posts had been
      stored either dry or in water. The bending test was carried out with and without
      preceding thermocycling of the CFRC posts. The cytotoxicity was evaluated by an
      agar overlay method after dry and wet storage. The values of flexural modulus and
      ultimate flexural strength were for dry stored CFRC post 82 +/- 6 GPa and 1154 +/
      65 MPa respectively. The flexural values decreased significantly after water
      storage and after thermocycling. No cytotoxic effects were observed adjacent to
      any CFRC post. Although fiber reinforced composites may have the potential to
      replace metals in many clinical situations, additional research is needed to
      ensure a satisfying life-span.

PMID- 9021334
TI  - Hypnosis compared with group therapy and individual desensitization for dental
      anxiety.
AB  - Effects of hypnotherapy (HT) and self-hypnosis training on extreme dental anxiety
      in adults aged 19-65 years were compared with group therapy (GT) and individual
      desensitization (SD) using scales of dental anxiety, dental beliefs, and fear of
      a next dentist (after specialist treatment). All experimental groups were
      demographically comparable and showed reduced anxiety and improved dental beliefs
      compared with 51 control patients. The 25 HT patients did not differ
      significantly in numbers of dropouts during training compared with the 30 GT
      patients or 68 SD patients. For patients completing treatment, HT (n = 22)
      reduced dental anxiety to the same degree as GT (n = 24) and SD (n = 60). HT and
      SD patients required more therapist hours per patient than did GT, but total
      dropouts at 1 yr after specialist treatment were significantly greater in HT (13/
      25) than for SD rehearsals (5/34) or SD video (8/32), but not GT (15/30).
      Hypnotizability was found to vary from patient to patient, with a direct
      relationship to time saved. But hypnotizability had an inverse relationship to
      STAI general anxiety level for those who went on to dentists after 1 year.
      Transference effects were noted for most HT dropout patients as an aversive
      response to continued dental treatment with other dentists than the specialist.

PMID- 9021335
TI  - Controlled study of the association of smoking with lactobacilli, mutans
      streptococci and yeasts in saliva.
AB  - The effect of smoking on salivary microbe levels was studied in 780 subjects by
      multivariate analysis, taking into account some confounding factors.
      Lactobacilli, mutans streptococci and yeasts were detected with Dentocult-LB,
      Dentocult-SM and Oricult-N tests. The explanatory variables considered were
      gender, presence of natural teeth, presence of removable denture, presence of
      decayed teeth, toothbrushing frequency, use of sugar in coffee or tea,
      consumption frequency of sugary products, secretion rate of stimulated and
      unstimulated saliva, buffering capacity of saliva, pH of saliva, oral hygiene and
      tobacco smoking habits. Smoking was strongly associated with higher lactobacilli
      counts and presence of yeasts, independently of oral status, hygiene or salivary
      factors. The relation between smoking and mutans streptococci was weaker. The
      overall associations of lactobacilli and yeasts with the study variables followed
      a very similar pattern.

PMID- 9021336
TI  - Inability of calcium hydroxide to induce reparative dentinogenesis at non
      peripheral sites of dog dental pulp.
AB  - The ability of 2 calcium hydroxide-containing materials to induce initiation of
      reparative dentinogenesis was tested at sites remote from the dentinogenically
      active regions of the pulp periphery. Pieces of the cements, Dycal and Life, were
      implanted in central parenchymal sites of dog dental pulps for periods of 6, 14
      and 42 days, respectively. Similar pieces were placed in peripheral capping sites
      as controls. The responses were analyzed by light and transmission electron
      microscopy. Induction of tubular dentin matrix lined with elongated and polarized
      odontoblast-like cells was only seen at peripheral capping sites. In response to
      the centrally implanted cements, only atubular hard tissue with lining fibroblast
      like cells was deposited.

PMID- 9021337
TI  - Expression of collagen and elastic fibers in duct-ligated submandibular glands of
      mice.
AB  - Atrophy of salivary glands may occur by ductal obstruction caused by calculus,
      infection or neoplastic processes, or as consequence of systemic diseases and
      aging. In the present work, we have used histochemical methods to study the
      expression of elastic and collagen fibers during experimental atrophy of the
      submandibular gland of mice. Glandular atrophy was accompanied by a rapid
      increase in collagen deposition in both septal and intralobular regions. The
      expression of elastic fibers was not significantly altered during atrophy: a
      discrete increase of elastic fibers was noted only around ductal structures. The
      results showed that experimental ductal obstruction is a useful in vivo model to
      study molecular events that take part in the remodeling of the extracellular
      matrix during atrophy of salivary glands.

PMID- 9021338
TI  - Age-dependent changes in insulin-like immunoreactivity in rat submandibular
      salivary glands.
AB  - In recent years, a growing interest had arisen in hormonal factors in salivary
      glands. We have investigated the changes in the content of an insulin-like
      immunoreactive (ILI) compound in the submandibular salivary glands of Sprague
      Dawley rats during physiological aging, in the range 15 days-27 months. The
      amount of ILI in the submandibular glands of young adult rats was found to be
      doubled in the post-natal period until the age of puberty and was maintained in
      senescence. No significant correlation was found between age-dependent variations
      in ILI levels of submandibular salivary glands and circulating insulin
      concentrations, further supporting previous indications that ILI is being
      synthesized in situ. It is possible that ILI could exert paracrine effects within
      the glands, as regards the development of other glandular structures during the
      first months of life, as well as the preservation of glandular function in
      senescent animals as well.

PMID- 9021339
TI  - Absence of binding of human salivary glycoprotein to human gingival fibroblast
      like cells in vitro.
AB  - The aim of this study was to determine whether human high molecular weight
      salivary glycoprotein binds in vitro to human gingival fibroblast-like cells.
      Primary monolayer cultures of 2 human gingival fibroblast-like cell lines were
      incubated with a high molecular weight fraction of salivary glycoprotein which
      expressed blood group A activity and glycoprotein-cell binding probed using an
      FITC-conjugated mouse monoclonal antibody to human blood group A antigen. Surface
      fluorescence of protein-treated cells was found to be no greater than that of
      untreated or serum-treated control cultures. As significant binding of salivary
      glycoprotein to gingival fibroblast-like cells does not occur in vitro, saliva
      mediated inhibition of fibroblast attachment to hydroxyapatite is not dependent
      on specific ligand-lectin interactions.

PMID- 9021340
TI  - X-ray diffraction study of crystalline phases of calcium sulphate in alginate
      impression materials.
AB  - In the present study the crystalline phases of calcium sulphate present in
      various commercially available alginate impression materials were identified by
      means of x-ray diffraction. The diffractograms obtained indicated that the
      predominant crystalline phase in most materials was calcium sulphate dihydrate
      and confirmed the presence of calcium sulphate hemihydrate in some products.

PMID- 9021341
TI  - Multistep treatment concept of transsexual patients.
AB  - Here we present a pragmatic multistep approach for the treatment of transsexual
      patients. The importance of an individually designed cross-gender hormone
      replacement therapy embedded in a multidisciplinary treatment concept, provided
      by psychiatrists, endocrinologists and surgeons, is demonstrated. Following this
      concept outcome of therapy has been improved in the last years. Over the last 5
      years we have gained substantial experience in the cross-gender hormone treatment
      of transsexual patients. By continuous follow-up examinations and therapy
      adjustment the risk of side effects accompanying this therapy has been
      significantly minimized. This report is designed as a guideline to the clinical
      endocrinologist for the handling and treatment of transsexual patients.

PMID- 9021342
TI  - The KID Study. III: Impact of inpatient rehabilitation on the metabolic control
      of type I and type II diabetics--a one-year follow-up.
AB  - The Kissingen Diabetes Intervention Study (KID) evaluated 1050 diabetic patients
      of the German Federal Insurance Institution for Salaried Employees (BfA) admitted
      for inpatient rehabilitation. The data for the prospective longitudinal study
      (which was collected in a single center) relate to the structure of the patient
      cohort, socio-economic and psychological factors and the mode of medical
      management at the time of admission and discharge. Data regarding the same
      variables was checked by random testing six and twelve months after discharge and
      used in this part of the study. This cohort of patients is especially interesting
      for aspects of health policy because it comprises rather young diabetics engaged
      in highly qualified professional work. Therapy modifications entailing a more
      intensive insulin regimen were necessary in 20.7% of all type I diabetics. Most
      of these alterations were maintained over the following 12 months of management
      by the general practitioner. Improvement of HbA1 levels was related to the number
      of daily insulin administrations. The results obtained during inpatient treatment
      in patients on ICT are maintained even one year after their discharge. For type I
      diabetics, the first training measure especially results in a long-term
      improvement of the metabolic situation, whereas patients who have already
      received training several times previously benefit continuously less with
      increasing repetition of training. After twelve months the intensified insulin
      therapy of type I diabetics had no further effect on the BMI or the already
      previously normal serum lipids. In 55.5% of all type II diabetics, the therapy
      had to be modified. Inpatient rehabilitation resulted in raising the low number
      of type II diabetics treated just with diet by 5.3%. This proportion was again
      slightly reduced 12 months later. During inpatient residence the number of
      overweight type II diabetics treated with drugs was reduced both in the group on
      oral hypoglycemics and in the group on pre-mixed insulin, according to the weight
      loss achieved. On the other hand, it was often necessary to intensify the usual
      insulin regimen twice daily in the group of younger patients with normal body
      weight. These modifications were maintained twelve months after the stay in
      hospital for most of these patients. Virtually all type II diabetics on oral
      hypoglycemics are overweight as a reflection of too early prescriptions of oral
      hypoglycemics which often neglects the chance of a dietary management only. In
      this group, therapy modifications were directed towards treatment with diet only
      and with oral hypoglycemics having an extra-pancreatic action. On metformin, the
      HbA1 was reduced by 0.3% and the BMI by 0.9 kg/m2 even 12 months later. In the
      90% of type II diabetics previously treated with sulphonylureas (almost
      exclusively glibenclamide), re-modification of therapy from metformin back to the
      old regimen (16:9%) was especially high. This is probably due to the uncertainty
      with and general restrictions in the prescription of metformin in the relevant
      period 1991 to 1995. The results 12 months after inpatient treatment show the
      small improvement of HbA1 and serum lipids as already seen in other larger
      interventional studies. The BMI does not change significantly within the
      relatively short follow-up period. The best long-term results are achieved by a
      combined therapy with sulphonylurea compounds and metformin. The KID study
      demonstrates major deficits in intensifying the insulin regimen of type I
      diabetics and in the individual adaptation to therapy of type II diabetes in
      Germany, even when younger patients of higher professional status are considered.
      Interventional inpatient rehabilitation improves their metabolic situation with
      lasting effect and can compensate deficits in outpatient management by the
      general practitioner. However, future concepts have to be improved at all levels
      of diabetic management, with a view to achieving an optimum interaction.

PMID- 9021343
TI  - Activation of human platelet protein kinase C-beta 2 in vivo in response to acute
      hyperglycemia.
AB  - Protein kinase C (PKC) is known to be activated in experimental model systems by
      elevated glucose and may play an important role in the pathogenesis of diabetic
      complications. Since there is no information about its role in humans in vivo we
      investigated the activation of PKC in human thrombocytes during infusion of
      glucose and insulin in normal controls and in 19 NIDDM patients by determining
      membrane and cytosol levels of PKC beta 2 using immune blots. In the 27 subjects
      investigated (8 controls, 19 NIDDM) membrane-associated levels of PKC beta 2
      increased significantly after 60 and 150 min (p < 0.005). In controls an increase
      of membrane and of cytosolic PKC beta 2 occurred upon elevation of glucose by 5.5
      mmol/L or more and the membrane association persisted for at least 60 min. In
      NIDDM glucose was elevated by 7.5-10 mmol/L during infusions. Increases of both
      membrane and cytosolic PKC beta 2 (< 20%-300%) occurred in 10 NIDDM patients
      suggesting that both, translocation and increased synthesis of PKC beta 2 were
      stimulated by glucose. Nine other patients showed no alteration (i.e. < 20%) of
      PKC beta 2. The 2 groups were similar regarding parameters of diabetes control,
      baseline glucose and glucose elevation during the test. However, the PKC beta 2
      responsive group had lower levels of serum triglycerides (1.39 +/- 0.19 vs. 2.32
      +/- 0.34 g/L; p = 0.038). To assess whether absolute levels of PKC were altered
      in human diabetes, platelet levels of PKC alpha, beta 1 and beta 2 were
      determined in 22 controls and 25 NIDDM subjects with poorly controlled diabetes
      (HbA1c = 9.8 +/- 0.36%). Cytosolic levels of PKC alpha were significantly
      decreased by 27% compared to controls in NIDDM but there was no change of PKC
      beta 1 or PKC beta 2. We conclude that 1. acute elevation of glucose by 5.5
      mmol/L or more can activate PKC beta 2 translocation in controls and NIDDM
      patients in vivo irrespective of parameters of metabolic control. 2. NIDDM
      patients differ in their PKC beta 2-responses to glucose and 3. poor metabolic
      control leads to moderate downregulation of PKC alpha suggesting continued
      activation.

PMID- 9021344
TI  - Dissociation of plasma and urinary steroid values after application of stressors,
      insulin, vasopressin, ACTH, or dexamethasone in the Mongolian gerbil.
AB  - The amounts of cortisol and testosterone in the plasma or urine of Mongolian
      gerbils exposed to stress factors or treated subcutaneously with insulin (2 IU),
      vasopressin (1 IU), ACTH (6 IU) or dexamethasone (50 micrograms) were determined.
      Increased plasma cortisol was observed in animals stressed by ether anesthesia or
      immobilisation (1-4 hours), or treated with insulin, vasopressin or ACTH.
      Cortisol levels were reduced after dexamethasone administration. Plasma
      testosterone was elevated in animals stressed by ether anesthesia or handling
      plus seizure; no other treatment altered testosterone levels. An augmented
      cortisol excretion, which lasted one day, occurred in gerbils immobilised for one
      as well as for four hours. A much more prolonged stimulation of cortisol
      excretion, lasting three days, was seen in animals receiving ACTH or
      dexamethasone plus ACTH. Testosterone excretion was stimulated by ACTH and
      dexamethasone plus ACTH; it was not influenced by any other treatment. The
      present study shows that analysis of circulating steroid levels is the only
      reliable approach to assess the secretory activity of Mongolian gerbil adrenals
      or testes. In some experimental conditions (e.g. after stressor application or
      ACTH treatment) cortisol excretion may be used as an index of adrenal secretory
      function. In contrast, the striking differences between cortisol values present
      in plasma and urine of peptide-or dexamethasone-treated gerbils indicate that
      urinary cortisol does not reflect short-term changes of adrenal function.
      Similarly, the striking differences of testosterone values in plasma and urine
      indicate that urinary testosterone monitoring cannot be used to determine the
      secretory activity of gerbil testes.

PMID- 9021345
TI  - The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion
      in healthy male subjects.
AB  - The effects of three doses of a special Agnus castus extract (BP1095E1)--extracts
      from 120 mg, 240 mg and 480 mg of drug per day--were examined within the
      framework of a placebo-controlled clinical study of tolerance and prolactin
      secretion in 20 healthy male subjects during a period of 14 days. There was good
      tolerance during the study as regards the following: adverse effects, the effects
      on blood pressure and heart rate, blood count, Quick's test, clinical chemistry
      as well as testosterone, FSH and LH values. During each study phase the 24-hour
      prolactin secretion profile was measured from the penultimate to the final day,
      and the amount of prolactin release was monitored an hour after TRH stimulation
      on the last day. A significant increase in the 24-hour profile was registered
      with the lowest dose in comparison to placebo, the opposite being the case with
      the higher doses, i.e. a slight reduction. In contrast to the administration of
      placebo, the 1-hour AUC after TRH stimulation resulted in a significant increase
      with the lowest dose and a significant reduction with the highest dose. The
      results suggest effects of the special Agnus castus extract which are dependent
      on the dose administered and the initial level of prolactin concentration.

PMID- 9021346
TI  - Radioimmunoassay for the detection of leptin in human serum.
AB  - Human leptin, which is encoded by the obese (ob) gene, is secreted specifically
      from adipocytes and is involved in the regulation of satiety and energy
      consumption. We developed a radioimmunoassay for the determination of leptin in
      human serum using polyclonal antibodies generated in rabbits against a C-terminal
      fragment of leptin, leptin(126-140), coupled to hemocyanin. The sensitivity of
      the assay was app. 5 pmol/l leptin(126-140) equivalent to 0.5 fmol/tube. The
      intra-assay variation at 100 pmol/l was less than 4.8% and the interassay
      variation less than 8.3%. Dilution curves of serum samples containing high levels
      of leptin(126-140) were parallel to the standard curve. Following G-50 Sephadex
      chromatography a single specific peak was detected at app. 16 kd. The assay
      procedure compared well to a commercially available assay (Linco, St. Louis, USA)
      using polyclonal antibodies directed against the intact recombinant protein (R =
      0.96; p < 0.0001). Serum levels were significantly higher than plasma levels
      (app.20%) over a wide range of the standard curve. Levels of serum leptin126-140
      immunoreactivity were not altered by meals and no day-to-day variation was found.
      In a group of 148 healthy female and 108 healthy male subjects with a BMI between
      18.2 and 40 kg/m2 there was a significant difference between sexes with higher
      circulating serum levels in female than in male subjects when tested for
      identical BMI (p < 0.001). Serum leptin levels in both male and female subjects
      were positively related to BMI (p < 0.001) when analysed for lean and obese
      subjects whereas in lean subjects this relation was not apparent. No relation of
      serum leptin levels and age was detectable in subjects with a BMI up to 30 kg/m2.
      These data support an important role of leptin in the regulation of body fat
      stores and BMI which is modulated by gender specific factors.

PMID- 9021347
TI  - Ligand-induced rapid desensitization causes structural alteration of rat ovarian
      LH/hCG receptor.
AB  - The role of the physical state of ovarian membranes was studied in the process of
      the early desensitization of the LH/hCG receptor. Thirty min after injection of a
      desensitizing dose of hCG to rats, the hCG-responsive adenylylcyclase activity
      was reduced, whereas hCG binding to ovarian membranes was still normal. Early
      desensitization decreased rigidity of membrane lipids, determined by fluorescence
      polarization of DPH. Possible structure-functional properties of the LH/hCG
      receptor were analyzed by thermal perturbation technique. Desensitization
      decreased thermal stability of the LH/hCG receptor in membranes and in
      proteoliposomes. Desensitization modified the quenching of protein fluorescence
      and intrinsic fluorescence spectral properties of membranes. The Stern-Volmer
      constants for control and desensitized membranes were found to be 4.3 and 5.5,
      respectively, indicating that desensitization elevated the accessibility of
      fluorophores for acrylamide. The changes of the physical properties of membranes
      resulting from desensitization was exhibited solely in the treatment with hCG in
      vivo, but not in vitro. The results suggest that the hCG-induced alteration of
      the physical state of luteal membranes may be a requirement for the induction of
      changes that lead to desensitization.

PMID- 9021348
TI  - Expression of GH, TSH beta, LH beta and FSH beta genes during fetal pituitary
      development in the pig.
AB  - The development of the anterior pituitary gland involves the proliferation and
      differentiation of ectodermal cells in Rathke's pouch to generate distinct cell
      types, each of which produces its corresponding trophic hormone. Studying
      pituitary development will therefore reveal novel aspects of organogenesis. In
      the present study, we examined by in situ hybridization the expression of genes
      for anterior pituitary hormones during development of the fetal pig pituitary. We
      found that the beta-subunit gene of thyroid-stimulating hormone (TSH beta) was
      first expressed at E40, (E = day of embryonal/fetal life), growth hormone (GH)
      mRNA appeared between E40 and E50, and the gonadotrophin genes (LH beta and FSH
      beta) were expressed at E50. The transcripts for TSH beta, LH beta and FSH beta
      were abundantly expressed at about E80, while GH mRNA continued to be richly
      expressed until after birth. The GH gene was first expressed in the mantle layer
      of the anterior lobe, while the TSH beta and gonadotrophin (LH beta and FSH beta)
      mRNAs were found in the central and the basal regions of the anterior lobe,
      respectively. All of these mRNAs (GH, TSH beta, LH beta, and FSH beta) remained
      concentrated until the end of gestation in the area where they first appeared.
      The distinctive pattern of developmental expression of these hormone genes in the
      fetal pig anterior pituitary makes this tissue an excellent system in which to
      study tissue-specific gene activation and regulation.

PMID- 9021349
TI  - The donor's right to retire. Second pregnancies and the donor's right to retire.

PMID- 9021350
TI  - Psychological factors relating to semen donation: a comment.

PMID- 9021351
TI  - Posthumous assisted reproduction. Posthumous assisted reproduction (PAR): cancer
      patients, potential cases, counselling and consent.

PMID- 9021352
TI  - Ethics of sex selection for family balancing. Why balance families?

PMID- 9021353
TI  - Time to revolutionize ovarian stimulation. Ovarian stimulation.

PMID- 9021354
TI  - Sequential step-up and step-down dose regimen: an alternative method for
      ovulation induction with follicle-stimulating hormone in polycystic ovarian
      syndrome.
AB  - This study was designed to compare both the effectiveness and safety of two low
      dose gonadotrophin regimens (step-up versus sequential step-up and step-down) for
      ovulation induction in polycystic ovarian syndrome (PCOS) patients. In all, 56
      infertile clomiphene citrate-resistant PCOS patients were included in this
      prospective randomized study. A total of 38 cycles were conducted with a classic
      step-up protocol, whereas for 35 cycles the follicle-stimulating hormone (FSH)
      threshold dose was reduced by half when the leading follicle reached 14 mm in
      diameter (sequential protocol). Serum oestradiol, progesterone and luteinizing
      hormone concentrations and follicular growth rate were evaluated during the
      cycle. At the time of human chorionic gonadotrophin administration, cycles
      treated with sequential protocol exhibited significantly lower oestradiol
      concentrations [434 +/- 45 versus 593 +/- 67 pg/ml (mean +/- SEM)] and the number
      of medium-sized (14-15 mm) follicles was significantly reduced (0.3 +/- 0.1
      versus 0.8 +/- 0.2) compared with cycles treated with the classic step-up
      protocol. Moreover, in these cycles serum luteal oestradiol concentrations were
      decreased significantly (350 +/- 77 versus 657 +/- 104 pg/ ml) compared with the
      classic step-up protocol. A sequential step-up and step-down protocol seems to be
      a safe and effective regimen for ovulation induction in PCOS patients. Decreasing
      the FSH dose following step-up follicular selection may be an alternative method
      to avoid multifollicular development.

PMID- 9021355
TI  - Effect of mifepristone (RU486) on the pituitary response to gonadotrophin
      releasing hormone in women.
AB  - Mifepristone interrupts folliculogenesis in women but the mechanism is not clear.
      Previous studies have investigated the effect of this compound on gonadotrophin
      secretion and have provided conflicting results. To study further the effect of
      mifepristone on basal and gonadotrophin-releasing hormone (GnRH)-induced
      gonadotrophin secretion, 12 normally ovulating women were investigated during two
      consecutive menstrual cycles, comprising an untreated cycle (control) and a cycle
      treated with mifepristone. All women were treated with mifepristone on days 2-8
      at the dose of 100 mg (group 1, eight women) or 10 mg per day (group 2, six
      women). Two women were treated with both regimens in two different cycles. On day
      8 of both cycles, the women received two GnRH pulses of 10 micrograms each 2 h
      apart. Blood samples in relation to the first GnRH pulse were taken at-15, 0, 30,
      60, 120, 150, 180 and 240 min. In group 1, the increase in luteinizing hormone
      (delta LH) in response to GnRH was significantly attenuated from 30 to 180 min,
      while the increase in follicle stimulating hormone (delta FSH) was attenuated
      only in response to the second GnRH pulse. No significant decrease in delta LH
      and delta FSH response to GnRH was seen during treatment with the 10 mg dose
      (group 2). In group 1, serum oestradiol and inhibin-A concentrations after day 8
      were lower than in the control cycles and the LH peak was postponed by 7 days on
      average. Basal LH values increased significantly on day 8 in both groups, while
      FSH values did not change significantly compared with the control cycles. A
      significant increase in serum progesterone and cortisol values occurred during
      the treatment only in group 1. Mid-luteal values of inhibin-A were significantly
      lower in cycles treated with 100 mg mifepristone than in the control cycles. We
      conclude that the disruption of folliculogenesis by mifepristone cannot be
      explained by a decrease in basal FSH concentrations during the critical period of
      follicle recruitment and selection. It is possible that mifepristone exerts its
      effect at the level of the ovary. It is also suggested that progesterone during
      the follicular phase of the cycle may participate in the control of the self
      priming action of GnRH on the pituitary.

PMID- 9021356
TI  - Midluteal immunoreactive alpha-inhibin serum concentrations as markers of luteal
      phase deficiency.
AB  - The present prospective clinical study was undertaken to determine the usefulness
      of midluteal phase serum immunoreactive alpha-inhibin concentrations as markers
      of luteal phase deficiency and whether they are better indicators of biopsy
      confirmed luteal phase defect than serum progesterone. Consecutive patients (n =
      138) with regular menstrual cycles attending our Infertility Clinic (experimental
      group) and 15 fertile women who were requesting contraception and had regular
      menstrual patterns (control group) were included. In all women (patients and
      controls), basal body temperature, midluteal serum concentrations of oestradiol,
      prolactin, progesterone and immunoreactive alpha-inhibin, and premenstrual
      endometrial biopsy were used in the same cycle to assess luteal function. Out-of
      phase secretory endometria were detected in 15 of the 138 patients. Thus,
      hormonal concentrations were compared between the following three groups of
      women: group 1 (n = 15), infertile patients with defective secretory endometria;
      group 2 (n = 123), infertile patients with normal secretory endometria; and
      controls (n = 15), fertile women with normal secretory endometria. Midluteal
      serum concentrations of progesterone, immunoreactive alpha-inhibin, oestradiol,
      and prolactin of the two groups studied were similar to those of the control
      group of fertile women. Our results indicate that midluteal serum inhibin
      determination does not accurately reflect histological maturation of the
      endometrium and it is not a better indicator of endometrial luteal phase
      deficiency than midluteal serum progesterone concentration.

PMID- 9021357
TI  - Diversity of the blocking effects of antisperm antibodies on fertilization in
      human and mouse.
AB  - The blocking effects of complement-dependent sperm immobilizing antibodies in the
      sera of infertile women and monoclonal antisperm antibodies against humans and
      mice on fertilization were investigated. The hemizona assay (HZA) and sperm
      penetration assay (SPA) were used to study the inhibitory effects of sera from 22
      infertile patients positive for sperm immobilizing antibodies. Use of these tests
      allowed us to differentiate whether the antibody blocked sperm-zona pellucida
      tight binding and/or sperm penetration into the ooplasm. The zona pellucida
      penetration assay (ZPA) was also used to study the effects of four monoclonal
      antibodies (mAbs) on human sperm penetration into the zona pellucida. Seven mAbs
      against murine spermatozoa were tested for their inhibitory effects on in-vitro
      fertilization (IVF) and HZA in mice. Of 22 patient sera with sperm immobilizing
      antibodies, 21 (95.5%) inhibited HZA attachment and penetration, whereas this did
      not occur in any of 13 patient sera without these antibodies. However, 19 of 22
      (86.4%) patient sera with sperm immobilizing antibodies and eight of 13 (61.5%)
      patient sera without these antibodies inhibited the SPA. Two (2C6, 1G12) of four
      mAbs against human spermatozoa showed strong inhibitory effects in all the assays
      (HZA, ZPA and SPA). One mAb (3B10) did not inhibit HZA but blocked ZPA and SPA.
      Another mAb (H6-3C4) seemed to have no inhibitory effects on fertilization. Two
      (Vx 5 and Vx 8) of seven mAbs against murine spermatozoa inhibited IVF in mice
      but did not block mouse HZA. These findings suggest that antisperm antibodies
      block fertilization at specific stages. Some of them may inhibit sperm
      capacitation and thus prevent all processes of fertilization that follow. Some
      other antibodies may not affect capacitation and sperm binding to zona pellucida
      but inhibit the acrosome reaction, followed by the blocking of sperm penetration
      through zona pellucida and ooplasm.

PMID- 9021358
TI  - The 60 kDa heat shock protein in human semen: relationship with antibodies to
      spermatozoa and Chlamydia trachomatis.
AB  - The presence of the 60 kDa heat shock protein (hsp60) in seminal fluid and its
      relationship to sperm autoimmunity or a localized immune response to Chlamydia
      trachomatis were examined. Semen from 64 male partners of infertile couples with
      no history of a chlamydial infection were investigated. Hsp60 was identified by
      an enzyme-linked immunosorbent assay (ELISA) using a monoclonal anti-hsp60
      antibody bound to wells of a microtitre plate and a polyclonal anti-hsp60
      antibody for detection. Antisperm antibodies on motile spermatozoa were detected
      by immunobead binding, while antichlamydial immuno-globulin (Ig) A and IgG in
      seminal fluid were identified by a commercial ELISA (SeroELISA: Savyon
      Diagnostics, Beer-Sheva, Israel). RNA was purified from isolated seminal round
      mononuclear cells and tested for hsp60-specific mRNA by a reverse transcription
      polymerase chain reaction ELISA. Hsp60 was present in semen from nine (14.1%)
      men, 12 (18.8%) men had antisperm autoantibodies. 16 (25.0%) were positive for
      antichlamydial IgA and 17 (26.6%) had detectable hsp60-specific mRNA. The
      presence of hsp60 in semen correlated with the occurrence of antichlamydial IgA
      (P = 0.0005), hsp60 mRNA (P = 0.04) and antisperm antibodies (P = 0.05). Thus,
      hsp60 was present in a soluble form in semen primarily in men with evidence of
      immune system activation within their genital tract. The role of hsp60 in
      promoting or inhibiting immune responses within the genital tract remains to be
      determined.

PMID- 9021359
TI  - Mitotic chromosomal anomalies among 1210 infertile men.
AB  - Detailed medical and clinical examinations were carried out on 1608 men attending
      an infertility clinic to determine if any of those exhibiting abnormal
      semenograms also had any other readily identifiable clinical condition. In all,
      1210 men showed abnormal semenograms according to World Health Organization
      criteria. Karyotyping of the white blood cells in these 1210 men revealed 44
      (3.6%) individuals with either autosomal or sex chromosomal aberrations. However,
      no single characteristic feature of their semenogram or clinical condition was of
      any diagnostic value to predict the existence of a chromosomal anomaly.

PMID- 9021360
TI  - Intracytoplasmic sperm injection in infertile patients with structural chromosome
      abnormalities.
AB  - In the present study we investigated the results of cytogenetic analysis in male
      and female patients included in an intracytoplasmic sperm injection (ICSI)
      programme for severe male infertility as well as in conceptuses resulting from
      these ICSI treatments. In the 261 couples treated, 11 male (4.2%) and three
      female (1.2%) abnormal karyotypes were found, all consisting of structural
      chromosome anomalies. Chromosomal translocation exhibited the highest frequency
      (eight males and two females), and there were also three cases of chromosomal
      inversion (two males and one female) and one male with one additional marker
      chromosome. There was no difference in fertilization rates among couples with
      abnormal (n = 14) and normal (n = 147) cytogenetic results, and the rates of
      clinical pregnancy per ICSI attempt were 25.0% (5/20) and 20.6% (78/ 378)
      respectively. In pregnancies obtained in couples with normal karyotypes, all of
      the 108 fetuses were free of chromosomal abnormalities. Among the eight fetuses
      from couples with chromosome structural anomalies, three out of five and two out
      of three inherited from the cytogenetic defects found in their father or mother
      respectively. In this series of 83ICSI pregnancies there were no chromosomal
      abnormalities other than those inherited from the parents. These findings suggest
      that normal pregnancy rates can be obtained by ICSI in cases of chromosomal
      translocation in couples with severe male infertility. However, until further
      evaluations of available data can be performed, cytogenetic analysis must be
      conducted prior to ICSI in men with low sperm counts, and genetic counselling
      must include prenatal diagnosis for all growing conceptuses.

PMID- 9021361
TI  - Microsurgery and in-vitro fertilization and embryo transfer for infertility
      resulting from pathological proximal tubal blockage.
AB  - The aim of this study was to evaluate the prognosis for the patients after the
      treatment of infertility resulting from proximal tubal blockage using
      microsurgical tubocornual anastomosis and in-vitro fertilization (IVF) and embryo
      transfer complementarily. A total of 59 microsurgical operations (1986-1992) for
      infertility resulting from pathological proximal tubal lesions were analysed. The
      cumulative live birth rate was 52% for tubocornual anastomosis, 58% for bilateral
      operations and 28% for two-site operations. In all, 35 singleton babies were
      born. Of the 32 operated patients who did not deliver within 2 years of surgery,
      21 were treated by 66 IVF cycles; 12 babies were born. The live birth rate was
      18% per cycle and 57% per patient. Combining both treatment methods the
      cumulative live birth rate was improved up to 69% in the group of tubocornual
      anastomoses, up to 75% in the group of bilateral operations, and up to 57% in the
      group of two-site operations. Complementary use of microsurgery and IVF and
      embryo transfer improves the prognosis for selected infertile patients with
      pathological proximal tubal blockage. In the absence of pregnancy, IVF and embryo
      transfer should be commenced 1 year after surgery.

PMID- 9021362
TI  - Higher pregnancy rates with a simple method for fallopian tube sperm perfusion,
      using the cervical clamp double nut bivalve speculum in the treatment of
      unexplained infertility: a prospective randomized study.
AB  - The object of this study was to evaluate the efficacy of the newly developed
      cervical clamp double nut bivalve (DNB) speculum used for Fallopian tube sperm
      perfusion (FSP) with 4 ml of the inseminate, in comparison with standard
      intrauterine insemination (IUI) using a volume of 0.5 ml of the inseminate.
      Couples with unexplained infertility (n = 104), undergoing 202 cycles, were
      enrolled in this study. Cycles were assigned randomly to either IUI (group A, n =
      92) or FSP + DNB speculum (group B, n = 110). Ovarian stimulation was achieved
      using three different ovarian stimulation protocols in both groups. The age and
      follicular development of the patients were similar in both groups. The serum
      hormonal measurements and the endometrial thickness was also similar on the day
      of human chorionic gonadotrophin (HCG) administration. The mean (+/-SD) number of
      motile spermatozoa inseminated was 44.83 +/- 16.57 x 10(6) in group A and 42.68
      +/- 13.44 x 10(6) in group B. In group A (IUI). 11 clinical pregnancies (presence
      of gestational sac with heart beats) occurred (11.95% per cycle). In group B (FSP
      + DNB speculum) 29 clinical pregnancies occurred (26.36% per cycle). These
      differences were statistically significant (P < 0.001). The results of this study
      for the treatment of unexplained infertility indicate that this simple, well
      tolerated, inexpensive method of using the DNB speculum for FSP is more
      successful than standard IUI.

PMID- 9021363
TI  - Incidence of spontaneous abortion in clomiphene pregnancies.
AB  - The purpose of this study was to determine whether the use of clomiphene results
      in a higher incidence of spontaneous abortion than occurs naturally in subfertile
      patients. Reproductive outcomes of 1744 clomiphene pregnancies were compared to
      outcomes of 3245 spontaneous pregnancies in a prospective study. Abortion was
      classified as clinical if a sac was seen on ultrasound or if it occurred after 6
      gestational weeks, and as preclinical if a quantitative human chorionic
      gonadotrophin (HCG) was > or = 25 mIU and no sac was seen or abortion occurred
      earlier. The overall incidence of abortion was higher for clomiphene pregnancies
      (23.7%), compared with spontaneous pregnancies (20.4%) (P < 0.01). Preclinical
      abortions were increased by clomiphene for all ages (5.8 versus 3.9%, P < 0.01)
      and for age > or = 30 years (8.0 versus 4.9%, P < 0.001), but not for age < 30
      years (3.7 versus 3.0%). Clinical abortions were increased by clomiphene for age
      < 30 years (15.9 versus 11.2%) (P < 0.01), but not for age > or = 30 years (20.1
      versus 22.3%) or all ages (18.0 versus 16.4%). Clinical abortions occurred 22%
      less often following clomiphene compared with spontaneous pregnancies for
      patients with luteal insufficiency (18.3 versus 23.6%, P < 0.05). We conclude
      that the increase in abortion due to clomiphene is small and may be related to
      different causes for women aged < 30 and > or = 30 years, and also that
      clomiphene may decrease clinical abortions in patients with luteal insufficiency.

PMID- 9021364
TI  - Expression of progesterone receptor mRNA in the endometrium during the normal
      menstrual cycle and in Norplant users.
AB  - The expression of endometrial progesterone receptor mRNA during the human
      menstrual cycle and in Norplant users was studied using digoxigenin-labelled
      ribonucleic probes for in-situ hybridization on 6 microns paraffin embedded
      endometrial sections. The staining intensity was scored blind semi
      quantitatively. Blood ovarian steroid concentrations were measured in Norplant
      users. All data were analysed by analysis of variance. Glandular progesterone
      receptor mRNA concentrations were low during the menstrual-to-early proliferative
      stage but increased during the early-to-mid to late-proliferative stage then
      declined non-significantly over the secretory stage. No such variation was
      observed in stromal cells. Progesterone receptor mRNA concentrations were lower
      in Norplant than controls during early-to-mid to late-proliferative stages (in
      glandular epithelium and stroma) and during secretory stage (in stroma only).
      Norplant subjects with amenorrhoea had higher concentrations of stromal
      progesterone receptor mRNA but lower plasma oestrogen concentrations than
      subjects with breakthrough bleeding. The pattern of variation in progesterone
      receptor mRNA concentrations during the normal menstrual cycle resembles the
      published pattern for the receptor protein. The results demonstrate: (i) a
      differential sensitivity of glandular and stromal progesterone receptors to
      steroid regulation; (ii) in contrast to previous findings of an increase in
      immunoreactive progesterone receptor protein in Norplant endometrium,
      progesterone receptor mRNA concentrations in these tissues were reduced; and
      (iii) there was significantly more progesterone receptor mRNA in subjects with
      amenorrhoea than in those with breakthrough bleeding.

PMID- 9021365
TI  - Statistical modelling reveals demography and time are the main contributing
      factors in global sperm count changes between 1938 and 1996.
AB  - Declining sperm count reports have caused enormous concern to both the scientific
      community and to society. We reproduced the linear regression analysis and the
      quadratic model analysis using the 50 year sperm count data published in
      Carlsen's report and found that neither model adequately described the data. The
      reported decline in sperm count could be due to observational bias and
      overinterpretation of linear regression. In fact only 36% of the total
      variability in sperm count was explained by the linear model and 42% by the
      quadratic model. The linear model was no longer valid when three new European
      reports on sperm counts were included in the analysis. The quadratic model,
      however, suggested an upward trend of sperm count after 1975 (R2 = 0.48, P <
      0.0001). Factors other than the 'passage of time' may have contributed to the
      initial decline of sperm count. An immediate candidate was demography. Our
      analysis showed that sperm counts in USA were significantly higher in 1938-1956
      compared with those in 1957-1974 and 1975-1988, but not in the European or
      Asian/African/South American countries. The variability of the USA sperm count
      (1938-1988) explained by the linear and quadratic models was found to be 71 and
      70% respectively. The quadratic model importantly indicated that the sperm count
      in USA decreases asymptotically towards a limiting value and global sperm counts
      could be increasing since 1970. The non-uniform nature of the global sperm count
      change suggested that local variations in pollution, diet but not global warming
      were important determinants of reproductive health.

PMID- 9021366
TI  - Intracytoplasmic sperm injection (ICSI) for severe semen abnormalities:
      dissecting the tail of spermatozoa at the tip.
AB  - Recently, several investigators have emphasized that damaging the membrane of
      spermatozoa by compressing the mid-piece or cutting the mid-portion of the tail
      prior to injection yields better results than using motile spermatozoa in
      intracytoplasmic sperm injection (ICSI). Here we report our experience using a
      modified immobilization technique of dissecting the tail of the spermatozoon at
      the tip in 78 cycles on 60 patients. In 55 treatment cycles purely using this
      modified technique, 468 mature oocytes were injected. A total of 35 oocytes
      (7.5%) were injured. Of the intact oocytes, 282 (65.1%) were normally fertilized
      and 266 (94.3%) subsequently cleaved. A single pronucleus was observed in 16
      (3.7%) oocytes, and three pronuclei were noted in 11 (2.5%) oocytes. Embryo
      transfers were performed in 54 cycles, and 18 women (32.7%) achieved clinical
      pregnancies. In 23 cycles, we compared the effects of these three immobilization
      techniques on the sibling oocytes obtained from the same patient regarding normal
      fertilization, abnormal fertilization, and embryo cleavage and quality. The
      results were comparable among them. Seven pregnancies (30.4%) were achieved in
      this series. Dissecting a sperm tail at the tip is easily and quickly performed
      and achieves permanent immobilization. Compression of the mid-piece is also easy,
      but usually takes several actions to achieve immobilization. Cutting the tail at
      the mid-portion requires more skill. Therefore, dissecting the tail of the
      spermatozoon at the tip may provide an alternative method to immobilize the
      spermatozoon permanently prior to ICSI.

PMID- 9021367
TI  - Pregnancy achieved by intracytoplasmic sperm injection using cryopreserved semen
      from a man with testicular cancer.
AB  - A successful pregnancy was achieved by intracytoplasmic sperm injection (ICSI)
      using cryopreserved semen from a man with testicular cancer. He was a victim of
      right testicular seminoma, and was azoospermic after right orchidectomy and
      radiotherapy. The wife had had three successive failures of intrauterine
      insemination (IUI) using semen that was cryopreserved before radiotherapy. The
      couple then underwent in-vitro fertilization (IVF) treatment. ICSI was performed
      because the sperm motility was extremely poor after thawing. Eight of 12 injected
      oocytes had normal fertilization and embryo cleavage. After replacement of four
      embryos, a singleton pregnancy developed. She delivered a healthy male baby at 39
      weeks gestation. In addition to IUI and IVF, ICSI further provides male patients
      with cancer an improved chance of fathering a child. Any men diagnosed with
      cancer who have not yet finished their families should have their spermatozoa
      frozen before treatment, regardless of its quality.

PMID- 9021368
TI  - A morphological and functional study of the effect of slow freezing followed by
      complete in-vitro maturation of primary mouse ovarian follicles.
AB  - Mechanically isolated intact early preantral follicles (100-130 microns diameter)
      from 14 day old mice were cryopreserved by a slow freezing protocol with dimethyl
      sulphoxide and then matured in vitro for 12 days after rapid thawing. Minor
      freeze damage observed after 1 day of in-vitro culture included ablation of the
      theca cell layer and granulosa cell dehydration, resulting in disruption of
      intercellular contacts with the oocyte and between granulosa cells. Of the
      follicles, 24% were irreversibly damaged and had a collapsed oocyte. The
      remaining majority of the follicles had an intact oocyte as evaluated by
      ultrastructural analysis. Follicles with an intact oocyte were cultured in vitro
      and, after an initial retarded development, the final number of fully grown
      oocytes ovulated in vitro was not different from that of unfrozen controls.
      Cryopreserved early preantral follicles matured in vitro responded to stimulus
      with human chorionic gonadotrophin in a similar way to controls, with
      mucification of the oocyte-cumulus complex, germinal vesicle breakdown and
      extrusion of the first polar body of the oocyte. These cryopreserved, in-vitro
      matured oocytes had the potential to fertilize and develop to hatched
      blastocysts.

PMID- 9021369
TI  - In-vitro maturation, fertilization and embryo development of immature oocytes
      from early preantral follicles from prepuberal mice in a simplified culture
      system.
AB  - A simplified culture system was developed for the in-vitro maturation of early
      preantral mouse ovarian follicles. The follicles were cultured singly in 20
      microliters droplets under oil in medium supplemented with recombinant follicle
      stimulating hormone (r-FSH) at 37 degrees C and 5% CO2 in air. The follicles grew
      and became attached to the bottom of the dish, progressively lost their spherical
      structure by outgrowth of the granulosa cells through the basal membrane and
      developed follicles with antral-like cavities. The normal three-dimensional
      follicular structure was lost but all components, i.e. theca, granulosa and
      oocyte, remained functional, as was proven by the oestradiol, inhibin and
      progesterone secretion patterns. Follicle survival exceeded 80% and histological
      analysis proved the absence of atresia and cell death in granulosa cells up to
      day 16. Oocytes of 55 (+/-4) microns diameter on the day of isolation reached 74
      (+/-3) microns by day 16 of culture. The optimal moment for inducing the final
      meiotic maturation with human chorionic gonadotrophin was investigated: the
      highest absolute numbers of metaphase II oocytes were obtained on days 12 and 14
      (39 and 41%). The fertilizing potential of the in-vitro matured oocytes was
      comparable to in-vivo matured controls. A 50% hatched-blastocyst development rate
      was observed.

PMID- 9021370
TI  - Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary
      during follicular development, ovulation and luteal formation.
AB  - Nitric oxide (NO) has emerged as one of several important intraovarian regulatory
      factors. In particular, NO has been implicated in the processes of ovulation and
      atresia-related apoptosis. The aim of the present study was to investigate the
      presence and distribution of the NO-generating nitric oxide synthase (NOS)
      enzymes in the ovary during follicular development, ovulation and luteal
      formation of the equine chorionic gonadotrophin (ECG)/human chorionic
      gonadotrophin (HCG)-primed rat. NADPH diaphorase activity was used as a
      histochemical marker for NOS within the ovary. Diaphorase reactivity was most
      abundant in the stroma (S) of the ovary and in the theca (T) layer of the
      follicle. In luteinized ovaries, weaker diaphorase reactivity was present within
      the corpora lutea (CL). Two different isoforms of NOS, the constitutively
      expressed endothelial NOS (eNOS) and the inducible isoform of NOS (iNOS), were
      immunolocalized in ovaries of immature rats and in ECG/HCG-primed rats during the
      periovulatory period from HCG injection until 2 days after ovulation. In
      addition, ovarian concentrations of eNOS and iNOS were quantified by
      immunoblotting. Immunoblotting with a monoclonal anti-eNOS antibody demonstrated
      the presence of eNOS mainly in the residual ovary (ROV) during the periovulatory
      period. In luteinized ovaries, higher concentrations of eNOS were seen in CL,
      while those in the ROV at this stage were lower than in the periovulatory ovary.
      Immature ovaries contained diminutive amounts of eNOS, detectable mostly in the
      ROV compartment. In contrast, iNOS was barely detectable during follicular
      development to the preovulatory stage. A slight elevation of iNOS was observed in
      the granulosa cells at 6 h after the HCG injection. The levels of iNOS during the
      luteal phase were also low. Immunohistochemical analysis using polyclonal eNOS
      and iNOS antibodies revealed the localization of these two isoforms primarily in
      the S and the T of the periovulatory ovary. In luteinized ovaries, positive
      immunoreactivity was also seen within the CL. With a monoclonal antibody against
      eNOS, intense immunoreactivity was observed in the S, T and within CL. There was
      a particularly strong staining in blood vessels. These data demonstrate the
      presence of an intraovarian NO-generating system. The localization of this system
      to the S, T and CL suggests a role for NO in the ovulatory process and in the
      regulation of CL function.

PMID- 9021371
TI  - Human follicular fluid inhibits the binding of human spermatozoa to zona
      pellucida in vitro.
AB  - The effect of human follicular fluid on human zona pellucida binding of
      spermatozoa was investigated using the hemizona binding assay (HZA). This effect
      was compared to that of progesterone, a known component of human follicular
      fluid. Exposure of spermatozoa to 25% pooled human follicular fluid for 1 h
      significantly reduced the number of spermatozoa bound to zona pellucida when
      compared to those without human follicular fluid treatment (149.1 +/- 30.7 versus
      177.1 +/- 33.8, P < 0.01). The same phenomenon was observed after 3 h of
      treatment. The corresponding numbers of bound spermatozoa were 140.4 +/- 19.1 and
      200.2 +/- 23.4 (P < 0.0001). Progesterone (1.0 microgram/ml) stimulated the zona
      pellucida-binding capacity of spermatozoa significantly under the same conditions
      (P < 0.01). The numbers of bound spermatozoa after 1 and 3 h progesterone
      treatment were 235.5 +/- 44.7 (control, 168.1 +/- 32.9) and 204.3 +/- 27.4
      (control, 162.3 +/- 20.1) respectively. HZA comparing the effects of human
      follicular fluid and progesterone at concentrations equivalent to those found in
      human follicular fluid using matching hemizonae confirmed the inhibitory effect
      of human follicular fluid on sperm binding to zona pellucida (80.4 +/- 28.4
      versus 149.8 +/- 35.2, P < 0.05). This inhibitory effect was also found in
      another eight individual human follicular fluid samples. Both human follicular
      fluid and progesterone did not affect the motility and viability of the treated
      spermatozoa when compared to the controls with the same incubation period.
      Although more spermatozoa underwent the acrosome reaction after 1 and 3 h of
      human follicular fluid treatment than in the control, the extent was comparable
      to those after progesterone treatment. These results suggested that human
      follicular fluid inhibited the zona pellucida-binding capacity of spermatozoa in
      vitro. This inhibitory effect of human follicular fluid was not mediated by
      progesterone, and did not result from the effects of human follicular fluid on
      sperm motility, viability and acrosome reaction.

PMID- 9021372
TI  - Non-enzymatic formation of formaldehyde in mouse oocyte freezing mixtures.
AB  - Three cryoprotectant solvents, dimethylsulphoxide, 1,2-propanediol and glycerol,
      were investigated for a non-enzymatic reaction product, formaldehyde. All three
      cryoprotectants demonstrated a direct relationship between increasing solvent
      molarity and increasing formaldehyde concentration which was independent of
      temperature and protein (bovine serum albumin). Medium composition significantly
      influenced the formaldehyde concentration with HTF > T6 > M16 = M2. The
      formaldehyde could be effectively removed by reduced glutathione, cysteine and
      dithiothreitol with cysteine being the most effective scavenging agent. A
      reaction mechanism for this scavenging is proposed. The combination of cysteine
      and cryoprotectant reduced the zona pellucida 'hardening' effect in mouse
      oocytes.

PMID- 9021373
TI  - Direct assessment of cryopreservation of human spermatozoa using a cryomicroscope
      and computer-aided sperm analysis.
AB  - Use of a cryostage has enabled direct observation of human spermatozoa as they
      are cryopreserved and thawed. Crystallization and recrystallization events are
      readily observed. In combination with computer-aided semen analysis (CASA)
      equipment it was possible to determine the consequence of altering the cooling,
      freezing and thawing rates of a temperature-rate profile on sperm motility.
      Increasing the cooling rate to 50 degrees C/min resulted in significantly lower
      pre-freeze to post-thaw ratios for average path velocity (VAP, 13%), mean
      straight line velocity (VSL, 35%), mean linearity (LIN, 28%) and straightness
      (STR, 24%), while the ratio of the number of cells crossing the field of view
      (NCF) significantly increased (30%) compared to a standard freeze-thaw
      temperature rate profile. The NCF pre-freeze to post-thaw ratio was associated
      with the percentage of cell recovery after cryopreservation. Faster thaw rates
      resulted in better survival of the cells, perhaps due to the shorter time during
      which recrystallization occurred. The NCF ratios were significantly higher (33
      and 30% for thaw rates of 50 and 100 degrees C/min respectively) than for the
      standard profile samples. Previous studies on cell survival have shown a link
      between the cooling and thaw rates. The cryostage should prove invaluable in
      future studies to identify the causes of cryodamage to spermatozoa. When used in
      combination with CASA, changes to sperm function during cryopreservation can be
      accurately measured.

PMID- 9021374
TI  - Scanning electron microscopy of the zona pellucida of human oocytes during
      intracytoplasmic sperm injection (ICSI).
AB  - During intracytoplasmic sperm injection (ICSI) approximately 10% of all injected
      oocytes degenerate. The reason for this process is unknown. It has been
      speculated that the mechanical procedure of the insertion of the ICSI needle
      induces injuries to the zona pellucida which lead to the death of the cell. By
      scanning electron microscope (SEM), it could be shown that the surface structure
      of mature oocytes is extremely elastic so that the injection needle penetrates
      the zona pellucida without destroying the mesh-like or more compact surface. No
      tissue pieces or zona fragments were detectable. After a culture time of 15 min
      the penetration site on the zona was no longer easily visible. We believe that
      oocyte degeneration is not caused by the penetration of a glass needle into the
      ooplasm but by an injury to the meiotic spindle or by an excessive dose of fluid
      [polyvinylpyrrolidone (PVP) or medium] during sperm injection.

PMID- 9021375
TI  - The protective action of polyvinylpyrrolidone-Percoll during the cryopreservation
      of mouse 2-cell embryos and its effect on subsequent developmental potential post
      thaw in vitro and in vivo.
AB  - The effects of cryopreservation, in media containing (FS3+) or omitting (FS3)
      polyvinylpyrrolidone (PVP) in the form of Percoll (PVP-Percoll), on the survival
      of 2-cell mouse embryos was studied. Survival and zona pellucida disruption post
      thaw, growth (assessed by in-vitro culture until the blastocyst stage) and
      development in vivo (assessed by implantation and living fetus rates and the
      birth of live progeny) were all investigated. Initial post-thaw survival showed
      no statistically significant difference (P > 0.05) between FS3+ (91.1 +/- 9.8%)
      and FS3 (84.5 +/- 6.6%). However, there was a statistically significant (P <
      0.05) reduction in the incidence of zona damage when the freezing solution
      contained PVP-Percoll compared to the control (3.6 +/- 1.0 and 8.7 +/- 0.6%
      respectively) and a statistically significant (P < 0.05) greater number of
      embryos developing in vitro to the blastocyst stage (84.8 +/- 7.1 and 72.3 +/-
      6.1% respectively). The rates of implantation were not significantly different:
      72.2 +/- 7.0% for FS3+ and 51.2 +/- 30.7% for the non-frozen control group. The
      percentage of live fetuses was also similar between the experimental and control
      groups: 27.4 +/- 10.6 and 24.3 +/- 11.3% respectively. We conclude that the
      presence of polymers can protect embryos against cryoinjury and that PVP in the
      form of PVP-Percoll provides a non-toxic alternative to PVP in its native form,
      during the cryopreservation of mouse 2-cell embryos.

PMID- 9021376
TI  - Alleviation of the '2-cell block' and development to the blastocyst of CF1 mouse
      embryos: role of amino acids, EDTA and physical parameters.
AB  - The role of amino acids, ethylenediaminetetraacetic acid (EDTA), transferrin,
      oxygen, glucose, glutamine, taurine and ammonium in CF1 mouse zygote development
      in culture was examined. Non-essential amino acids and glutamine were shown to
      alleviate the 2-cell block in culture, and acted in synergy with EDTA to
      facilitate development to the blastocyst stage. In the presence of amino acids
      and EDTA, transferrin conferred no beneficial effect. Development of zygotes was
      significantly impaired if amino acids were removed from the collection medium,
      even when they were subsequently cultured in the presence of amino acids. Zygote
      development to the blastocyst stage was significantly improved when modular
      incubator chambers were used compared to using a conventional incubator, and when
      an oxygen concentration of 7% was used as opposed to 20%. Addition of taurine to
      medium containing non-essential amino acids had no effect on embryo development,
      whereas the removal of glutamine and/or glucose from the culture medium
      significantly reduced blastocyst cell number. Removal of glucose from the culture
      medium also resulted in a significant decrease in implantations. Ammonium,
      generated from the breakdown of amino acids, significantly reduced blastocyst
      development. EDTA was found to confer its beneficial effects during the first 48
      h of culture, and indeed was inhibitory during the second 48 h, resulting in loss
      of subsequent viability. In summary, the data demonstrate that development of CF1
      zygotes to the blastocyst stage is readily achievable. In the presence of non
      essential amino acids and glutamine the removal of glucose is detrimental to CF1
      mouse embryo development in culture and reduces subsequent viability. Optimal
      development and maintenance of viability requires more than one culture medium to
      support the preimplantation period.

PMID- 9021377
TI  - Immunohistochemical localization of extracellular matrix proteins in luteal phase
      endometrium of fertile and infertile patients.
AB  - The lack of expression of certain components involved in cell adhesion and
      migration is believed to contribute to endometrial dysfunction and implantation
      failure. The purpose of this study was to investigate whether luteal phase
      endometrium in women with unexplained infertility differs, with respect to
      specific extracellular matrix (ECM) proteins, from endometrium of normal fertile
      women. A panel of monoclonal antibodies to collagen type IV, fibronectin and
      laminin was used to characterize the localization of ECM components in the
      different endometrial compartments. Precisely timed endometrial biopsies obtained
      at 4, 7, 10 and 13 days following the luteinizing hormone surge were obtained
      from 22 normal fertile women (group 1) and 24 women suffering from unexplained
      infertility (group 2). Paraffin-embedded sections were labelled using the
      streptavidin-biotin alkaline phosphatase technique. In group 1, collagen type IV,
      fibronectin and laminin were absent from the luminal epithelium but present in
      stromal cells and the basement membrane of glands and blood vessels. In group 2,
      these components were absent from all endometrial regions using equivalent titres
      of antibody to those used in group 1. This suggests that the endometrium of women
      with unexplained infertility demonstrates defects in the distribution of certain
      ECM glycoproteins. A possible consequence of this defect may be implantation
      failure.

PMID- 9021378
TI  - Endometrial pattern in diethylstilboestrol-exposed women undergoing in-vitro
      fertilization may be the most significant predictor of pregnancy outcome.
AB  - The objective of this study was to compare prospectively pregnancy outcome as it
      is related to ultrasonic endometrial echo pattern in women exposed to
      diethylstilboestrol (DES) in utero by their mother's consumption with women not
      exposed to DES, all of whom were undergoing in-vitro fertilization (IVF).
      Pregnancy outcome relative to endometrial thickness and pattern was evaluated in
      540 cycles of IVF including DES (n = 50) and non-DES-exposed (n = 490) women.
      Endometrial patterns were designated as p1 = solid; p2 = ring; and p3 =
      intermediate. DES patients exhibited p1 more often than the majority of the non
      DES-exposed group. There was no significant difference in endometrial thickness
      among the cycles where p1 was noted when comparing the DES (10.3 mm) with the non
      DES-exposed (10.7 mm) groups. Notably, within the group exhibiting p1, no
      pregnancies occurred in the 18 cycles of DES-exposed women compared with a 39.2%
      clinical pregnancy and 36.5% delivery rate in the non-DES-exposed controls (P <
      0.0001 and P = 0.008 respectively). Pregnancy rates were not significantly
      different in the cycles where the other endometrial patterns were found when
      comparing the two groups. The impact of uterine shape on pregnancy outcome was
      also investigated. A T-shaped uterine configuration was noted in 11 out of 18
      (61.1%) cycles of DES-exposed women with pattern p1 compared with nine out of 23
      (39.1%) with pattern p2. Of cycles where a T-shaped uterus was demonstrated, none
      out of 11 (0%) with pattern p1 compared with four out of nine (44.4%) with
      pattern p2 resulted in pregnancy (P = 0.026). These data suggest that endometrial
      pattern is one of the most significant variables for pregnancy outcome in DES
      exposed women undergoing IVF.

PMID- 9021379
TI  - Endometrial thickness: individual and mean growth profiles for different hormone
      replacement regimens.
AB  - Currently, there is a paucity of data describing endometrial growth, with most
      studies concentrating on endometrial thickness immediately prior to implantation
      or embryo transfer. This study looked at the individual and combined growth
      profiles of 67 volunteers receiving three different hormone replacement regimens.
      Each treatment regimen was in excess of that considered necessary for optimal
      growth, and all promoted an endometrial thickness that would be considered
      satisfactory for embryo transfer. Three patterns of growth were identified, but
      overall there was a decrease in the rate of endometrial growth with duration of
      treatment. As expected, analysis of variance did not show a significant
      difference between the mean growth profiles for the three hormone replacement
      regimens. The correlation (r = 0.45, P < 0.0001) between rank order on day 3 and
      day 10 of treatment indicates that interim analysis during early treatment cannot
      accurately predict later thickness, but a doubling of endometrial thickness can
      be expected in most cases. A relationship between endometrial thickness and
      either the treatment dose or serum concentrations of oestradiol was not found.
      These findings suggest that manipulation of endometrial growth is not possible by
      adjustment of either the treatment dose or serum concentration. The findings
      indicate that treatment beyond 12 days does not promote either a clinically
      significant increase in endometrial thickness of an excessive thickness,
      suggesting that maintenance of an oocyte recipient in a pseudo-follicular phase
      is unlikely to be disadvantageous to implantation.

PMID- 9021380
TI  - Leuprolide in a 3-monthly versus a monthly depot formulation for the treatment of
      symptomatic endometriosis: a pilot study.
AB  - An open-label randomized pilot study was conducted to evaluate the efficacy and
      acceptability of 6 months treatment with leuprolide in a 3-monthly versus a
      monthly i.m. depot injection for the relief of chronic pelvic pain in women with
      endometriosis. A total of 30 women aged 18-38 years were allocated to the 3
      monthly depot arm (n = 15) or to the monthly depot arm (n = 15) after
      laparoscopic diagnosis of pelvic endometriosis. Mean (SD) deep dyspareunia scores
      according to a 0-3 point verbal rating scale decreased from 1.8 (0.9) at baseline
      to 1.3 (0.7) at the end of treatment in the 3-monthly depot group and from 2.1
      (1.2) to 1.3 (0.7) in the monthly depot group. Corresponding values in non
      menstrual pain scores fell from 2.1 (0.6) to 1.1 (0.3), and from 2.1 (0.8) to 1.2
      (0.4) respectively, without statistically significant differences between the
      groups. Serum luteinizing hormone (LH) and 17 beta-oestradiol concentrations were
      significantly suppressed at 12 and 24 weeks compared with baseline values,
      without differences between the groups. The monthly depot caused a slightly more
      marked inhibition of serum follicle stimulating hormone (FSH) levels with respect
      to the 3-monthly preparation. Mean (SD) endometriosis scores at baseline and at 6
      month follow-up laparoscopy were respectively 32.8 (25.1) and 12.2 (9.3) in the 3
      monthly depot group and 29.0 (22.7) and 13.1 (15.3) in the monthly depot group
      (paired t-test, P < 0.05). Mean percentage decrease in lumbar spine bone mineral
      density was 5.2% in the former and 4.9% in the latter subjects. In the 3-monthly
      depot group, 13 women graded the tolerability of their treatment schedule as
      "good' compared with seven in the monthly depot group (chi 2 = 5.40, P = 0.02).

PMID- 9021381
TI  - Expression of the 60 kDa heat shock protein in peritoneal fluids from women with
      endometriosis: implications for endometriosis-associated infertility.
AB  - Proinflammatory cytokines and activated macrophages and T lymphocytes have been
      detected in peritoneal fluids of women with endometriosis and may impair
      fertility. Expression of the 60 kDa heat shock protein (hsp60) is one mechanism
      leading to a localized activation of macrophages and T lymphocytes and cytokine
      release. Peritoneal fluids, obtained from 68 women undergoing a diagnostic
      laparoscopy, were assayed for hsp60. As independent evidence of local immune
      activation, the fluids were analysed for interferon gamma (IFN gamma). Fluids
      were also tested for antibodies to Chlamydia trachomatis because a chronic
      asymptomatic infection by this organism may also release hsp60. At laparoscopy,
      26 women were diagnosed with pelvic adhesions, 19 had endometriosis, 16 had a
      visibly normal pelvis, four had ovarian cysts while three had myomas. The
      prevalence of hsp60 was higher in peritoneal fluids from the women with
      endometriosis than in the other subjects (P = 0.005). Hsp60 was detected in seven
      (36.8%) of the endometriosis patients and in only one each of the women with
      adhesions, a normal pelvis or an ovarian cyst; all women with myomas were
      negative. Detection of IFN gamma in peritoneal fluids was highly correlated with
      the presence of hsp60 (P = 0.0003). IFN gamma was present in seven of nine
      (77.8%) women with hsp60 and in only five of 40 (12.5%) women lacking hsp60.
      Women with pelvic adhesions had an increased prevalence of immunoglobulin G
      antibodies to C.trachomatis compared with the other women (P = 0.01). There was
      no relationship between evidence of exposure to C.trachomatis and hsp60 in
      peritoneal fluids. These data suggest that hsp60 may be released into the
      peritoneal fluid as a consequence of implanted ectopic endometrium. Hsp60
      mediated immune activation may be one mechanism leading to endometriosis
      associated infertility.

PMID- 9021382
TI  - Trophectoderm projections: a potential means for locomotion, attachment and
      implantation of bovine, equine and human blastocysts.
AB  - The behaviour of bovine, equine and human blastocysts was studied in vitro by
      time-lapse videomicrography and computer imaging. This study revealed that
      cytoplasmic extensions of the trophectoderm ['trophectoderm projections' (TEP)]
      were expressed by embryos of all three species, prior to or during zona escape.
      Bovine and human blastocysts escaped their zonae with a combination of
      blastocoele expansion, collapse and re-expansion coupled with the penetration of
      the zona pellucida by TEP. In equine embryos, after several cycles of blastocoele
      expansion and collapse, trophectoderm ruptured the zona with the concomitant
      appearance of TEP. This study provides documentation that TEP are expressed by a
      diverse range of mammalian species, bringing the total number of species in which
      this phenomenon is found to six, since TEP are also known to be expressed by
      guinea-pig, hamster and rhesus monkey blastocysts, representing rodents,
      ungulates and primates. In all species studied, the dynamic nature (extension,
      retraction, and angular movement) of the TEP was similar, moving in an undulating
      manner with rapid cycles of extension and retraction. Because TEP appear to be a
      general feature of mammalian blastocysts, they are implicated in one or more key
      events in early development, namely zona escape, attachment and/or implantation.

PMID- 9021383
TI  - Effect of platelet activating factor on embryonic development and implantation in
      the mouse.
AB  - Platelet activating factor (PAF) was administered to female mice in order to
      investigate its effect on ovulation rate and on oocyte quality including their in
      vitro embryonic development, implantation and uterine receptivity. In experiment
      1, 4-week-old female mice were assigned to receive PAF or phosphate buffered
      saline for 4 consecutive days. On the second day of this treatment, pregnant
      mares' serum gonadotrophin was administered and human chorionic gonadotrophin
      (HCG) 48 h later, after which copulation occurred. Oocytes were collected on the
      following day and evaluated. The mean number of oocytes and zygotes (two
      pronuclear stage embryos) recovered from the PAF-treated group was not different
      from the control group (31 versus 27), but the proportion of zygotes was higher
      in PAF-treated group than in controls (83 versus 68%, P < 0.05, PAF versus
      controls). Although the rate of in-vitro first cleavage was not different in the
      two groups (82 versus 69% respectively), hatching was higher in the PAF-treated
      group than control mice (99 versus 83%, P < 0.01). In experiment 2, the in-vitro
      developed blastocysts from experiment 1 were transferred into the uterus of day 3
      pseudopregnant PAF-treated or control recipients. Three different combinations of
      intrauterine transfer were performed; PAF embryo to control recipient (PAF-->C: n
      = 19), control embryo to PAF recipient (C-->PAF: n = 19), and control embryo to
      control recipient (C-->C: n = 22). Implantation and abortion were assessed on day
      19 posttransfer. The implantation rate of C-->PAF (23.7%) was lower than C-->C
      (31.1%, P < 0.05), but was not different from PAF-->C (31.2%). Further, C-->PAF
      showed a higher abortion rate per embryo (29.6%) than PAF-->C (12.7%, P < 0.05),
      but was not different from C-->C (24.4%). In the present study, PAF
      administration enables females to produce oocytes with a higher potential for
      fertilization, in-vitro development and implantation, but has a detrimental
      effect on uterine receptivity to embryos.

PMID- 9021384
TI  - Ectopic pregnancy after in-vitro fertilization is characterized by delayed
      implantation but a normal increase of serum human chorionic gonadotrophin and its
      subunits.
AB  - We studied the dynamics of serum human chorionic gonadotrophin (HCG) and its free
      alpha (HCG alpha) and beta (HCG beta) subunits in 49 early pregnancies achieved
      by in-vitro fertilization (IVF) and embryo transfer. Of the 49 early pregnancies,
      nine were normal singleton pregnancies, 11 were twin pregnancies, 11 were
      ectopic, eight ended in a clinical (spontaneous) abortion and 10 ended in a
      preclinical abortion. The HCG, HCG alpha and HCG beta concentrations in serum
      were measured on days 12, 19 and 26 after embryo transfer. Most ectopic
      pregnancies could be distinguished from singleton (and twin) pregnancies on the
      basis of low HCG concentrations by 12 days after embryo transfer, but clinical
      abortions could not be distinguished from singleton pregnancies. In general, the
      measurement of HCG alpha and HCG beta and the molar ratios of the various forms
      provided only marginal additional value to that obtained from HCG, but on days 19
      and 26 after embryo transfer HCG alpha was the most sensitive indicator of a
      normal pregnancy after IVF and embryo transfer. We conclude that in ectopic
      pregnancies the concentrations of HCG, HCG alpha and HCG beta increase as
      expected but 1.5 days later than in normal pregnancies. This appears to be the
      result of a delay in implantation.

PMID- 9021385
TI  - Intrauterine sonographic assessments of embryonal liver length.
AB  - Our purpose was to evaluate embryonal liver length measurement using intrauterine
      sonography with a specially developed 20 MHz flexible catheter-based high
      resolution real-time miniature (2.4 mm outer diameter) ultrasound transducer in
      early first-trimester pregnancy. A total of 36 women about to undergo therapeutic
      abortion at 7-9.9 weeks gestational age and one abnormal pregnancy with fetal
      hydrops at 9 weeks were studied. The normal range of embryonal liver length for
      each day of pregnancy was determined. A relationship between embryonal liver
      length and crown-rump length measurements is described. A linear relationship was
      found between the menstrual age and embryonal liver length (R2 = 93.3%), and a
      normal range of embryonal liver length for estimating the growth of the embryonal
      liver during early first trimester pregnancy was generated. A normogram of
      menstrual age as predicted by embryonal liver length was also generated.
      Embryonal liver length was curvilinearly correlated with crown-rump length (R2 =
      92.3%). Embryonal liver length value (6.4 mm) in a case of fetal hydrops at 9
      weeks was above the normal range. These results may provide an additional
      measurement for the estimation of gestational age in the early first trimester of
      pregnancy. In this limited series one embryonal liver enlargement was
      demonstrated and, thus, there is a potential for its use in the detection of
      embryonal congestive heart failure. The value and potential applications of this
      new embryonal parameter are discussed.

PMID- 9021386
TI  - A comparison of methotrexate versus laparoscopic surgery for the treatment of
      ectopic pregnancy: a cost analysis.
AB  - This study was a cost analysis of direct medical costs of the methotrexate
      management versus laparoscopic surgery in the treatment of ectopic pregnancy. A
      total of 40 patients treated from January 1991 to October 1994 with methotrexate
      were compared with another 40 patients treated at the same hospital by
      laparoscopy from April 1986 to June 1994. Medical records for all these patients
      were received and hospital databases were used to retrieve information on cost.
      Treatment cost included the primary treatment, hospitalization and outpatient
      follow-up necessitated by treatment, complications and secondary treatment in
      cases of treatment failure. The cost related to diagnosis was excluded. The
      direct medical costs for methotrexate and laparoscopy groups were based on
      success rates of 72.5 and 95% respectively. The total cost of methotrexate
      treatment was Canadian $35,180 compared with Canadian $73,440 for the
      laparoscopic treatment. The mean +/- SD cost per patient was Canadian $880 +/-
      160 in the methotrexate group compared with Canadian $1,840 +/- 150 in the
      laparoscopic group (P < 0.001). The mean +/- SE cost per patient with
      methotrexate success was Canadian $330 +/- 67 compared with Canadian $2,330 +/-
      220 per patient with methotrexate failure (P = 0.001). A complete assessment of
      methotrexate treatment, including cost-benefit and cost-effectiveness, is
      warranted.

PMID- 9021387
TI  - Oxygen promotes contraction by endothelin-1 in human umbilical artery.
AB  - The influence of oxygen on the contractile response to endothelin-1 in the human
      umbilical artery was investigated in vitro. Segments of human umbilical artery
      were suspended in organ baths to record the circular motor activity induced by
      endothelin-1 at a pO2 of 12 kPascal (kPa) or 45 kPa. Endothelin-1 induced a
      concentration-dependent contraction which was significantly larger at 45 kPa O2
      compared with the contractile response at 12 kPa O2.

PMID- 9021388
TI  - Cytogenetic characteristics of ectopic pregnancy.
AB  - During a 12 month period, tissue was collected from 30 surgically managed
      patients presenting with vital ectopic pregnancies. Chorionic villi of the
      removed tissue were successfully karyotyped by (semi-) direct chromosome
      technique in 22 cases. Only one abnormal chromosomal complement, a triploidy
      (69,XXX) was found. As controls, 10 cases of intrauterine pregnancies were
      investigated, all showing a normal karyotype. These findings do not suggest an
      important role for chromosome abnormalities in the aetiology of vital ectopic
      pregnancies.

PMID- 9021389
TI  - Inhibin in extra-embryonic coelomic and amniotic fluids and maternal serum in
      early pregnancy.
AB  - Inhibins are present in maternal serum during pregnancy. However, the presence of
      inhibins in the compartments surrounding the fetus in early pregnancy is not well
      defined. Using novel specific enzyme-linked immunosorbent assays we have
      demonstrated that the bioactive dimeric inhibin forms, inhibin-A and inhibin-B,
      and the immunoreactive inhibin forms containing pro- and alpha C sequences are
      present in different amounts in the extra-embryonic coelomic and amniotic fluids
      and maternal serum between 8-11 weeks gestation. Of the bioactive dimeric
      inhibins, both inhibin. A (mean +/- SEM 236.0 +/- 24.8 pg/ml) and inhibin-B (62.0
      +/- 8.6 pg/ml) are present in extra-embryonic coelom whereas no dimeric inhibin
      is present in the amniotic fluid and only inhibin-A (360.2 +/- 32.9 pg/ml) is
      present in maternal serum. Furthermore, pro-alpha C-related immunoreactivity is
      present at high concentrations in the extra-embryonic coelom (591.7 +/- 60.5
      pg/ml), amniotic fluid (452.4 +/- 76.8 pg/ml) and maternal serum (539.4 +/- 39.5
      pg/ml). These findings would indicate that at this stage of gestation inhibin-A,
      inhibin-B and immunoreactive pro- alpha C-containing inhibin production are
      likely to arise from different sources including the fetus, placenta and fetal
      membranes and maternal sources including the ovary. Inhibins may be important
      regulators of fetal and placental development and involved in the establishment
      of pregnancy.

PMID- 9021391
TI  - Spontaneous resolution of ectopic pregnancy in a surrogate after oocyte donation
      and frozen embryo transfer.
AB  - A case of tubal pregnancy in a young and healthy woman participating in a
      programme of in-vitro fertilization (IVF) gestational surrogacy is reported. The
      gestational surrogate was the 30 year old fertile sister of a 25 year old patient
      affected by stage 1 ovarian cancer. After mandatory oncological consultation, the
      donor was recommended to prospectively undergo controlled ovarian
      hyperstimulation cycles for embryo banking before being treated by total
      hysterectomy. Available embryos were cryopreserved and after adequate endometrial
      preparation using artificial cycles of hormone replacement therapy, three thawed
      frozen embryos were transferred to the surrogate. At 17 days following embryo
      transfer the surrogate was noted to have a negative beta-human chorionic
      gonadotrophin (HCG) serum concentration. All medication was suspended and a few
      days later normal menstrual bleeding occurred. After 2 weeks, the beta-HCG
      concentrations, performed as part of routine follow-up evaluation, were showing
      signs of trophoblast activity (236 mIU/ml). Taking into account the stable
      condition of the patient, a decision was made to undertake expectant management.
      At 43 days after embryo transfer, a complete tubal abortion was apparently seen
      in the posterior cul-de-sac by ultrasound associated with a subtle and short
      lasting pelvic pain. We stress that this ectopic gestation was able to maintain
      prolonged viability in conditions of absent corpus luteum and exogenous steroid
      supplementation.

PMID- 9021390
TI  - Regulation of vascular adaptation during pregnancy and post-partum: effects of
      nitric oxide inhibition and steroid hormones.
AB  - Treatment of pregnant rats with the nitric oxide synthase inhibitor NG-nitro-L
      arginine methyl ester (L-NAME), has been shown to produce symptoms similar to pre
      eclampsia (i.e. elevated blood pressure, proteinuria and fetal growth
      retardation). After L-NAME infusion is initiated on day 17 or 18 of gestation,
      the blood pressure proceeds in a biphasic pattern (immediate rise, followed by a
      decline, then increasing again in the post-partum period). The blood pressure
      actually begins to rise prior to delivery on days 21-22, i.e. after progesterone
      withdrawal occurs, suggesting that these responses may be regulated by changes in
      steroid hormone concentrations during pregnancy. Therefore, we evaluated the
      effects of the different steroid hormones: progestins (progesterone,
      promegestone, levonorgestrel), antiprogestins (mifepristone), 17 beta-oestradiol
      or androgens (testosterone, dihydrotestosterone) on systolic blood pressure in
      pregnant, non-pregnant female and normal male rats with and without L-NAME
      treatment and spontaneously hypertensive male rats. The animals received
      continuous infusions of L-NAME (150 mg/kg/day) or vehicle through osmotic mini
      pumps and daily s.c. injections of steroid hormones. In pregnant rats the pump
      was inserted on day 17 or 18 of gestation and steroid hormone injections were
      started on the first day following delivery at term and continued daily until
      post-partum day 10. In non-pregnant female or male rats steroid hormone
      injections were initiated 5 days after the L-NAME pump was inserted. Systolic
      blood pressure was measured daily from the tail with a pneumatic tail-cuff
      device. R5020 (1.5 mg/kg/day) significantly attenuated the blood pressure
      elevation induced by L-NAME during the post-partum period. Similarly, it lowered
      blood pressure in L-NAME treated non-pregnant female rats or male rats. R5020
      also lowered blood pressure in spontaneously hypertensive male rats. Progesterone
      (6 mg/kg/day) had similar effects on blood pressure in the post-partum period,
      although it also lowered the blood pressure in control animals. Interestingly,
      administration of two different doses of levonorgestrel (0.3 and 1.5 mg/kg/day)
      did not decrease the blood pressure in either L-NAME-infused rats or controls.
      Mifepristone (RU486, 30 mg/kg/day) further increased blood pressure in L-NAME
      treated rats post-partum. 17 beta-oestradiol (30 micrograms/kg/day) had no effect
      on blood pressure in either L-NAME infused rats in the post-partum period or
      controls, whereas both testosterone (0.3 mg/kg/day) and dihydrotestosterone (0.3
      mg/kg/day) significantly attenuated the blood pressure increase after L-NAME,
      while raising the blood pressure in vehicle-infused animals. These results
      suggest that the control of systemic blood pressure during pregnancy may be
      modulated by steroid hormones. Progesterone may be the steroid hormone with the
      major action on vascular tension during pregnancy.

PMID- 9021392
TI  - The effect of positive semen bacterial and Ureaplasma cultures on in-vitro
      fertilization success.
AB  - A total of 342 couples planning to undergo in-vitro fertilization (IVF) were
      examined for the presence of bacteria in semen prior to and during the procedure.
      Pregnancy rates were analysed retrospectively to ascertain any adverse affects if
      > 10000 colony forming units (CFU)/ml bacteria were detected in the semen sample.
      The most common bacteria isolated from semen were Enterococcus spp. (73%). The
      presence of these bacteria did not affect the pregnancy rate of the patients with
      positive cultures prior to (32%) or during (37%) the IVF procedure compared with
      those patients in whom no bacteria were detected (32%). Those patients with semen
      cultures positive for Escherichia coli prior to the IVF procedure, but which
      cleared after treatment had a higher pregnancy rate (60%) compared with those
      patients who were positive for E.coli at the time of the attempt. The group of
      patients with Staphylococcus aureus in the semen at the time of IVF also
      demonstrated a low pregnancy rate (17%). Of the patients. 36 (11%) had positive
      Ureaplasma cultures from the screening test carried out on the semen and 22%
      became pregnant after successful treatment. None of the three patients with
      persistently positive cultures became pregnant. In conclusion, the presence of
      Enterococcus in semen does not affect pregnancy rates following IVF. E.coli,
      S.aureus and Ureaplasma urealyticum may have a negative effect and should be
      treated.

PMID- 9021393
TI  - Infertility among human immunodeficiency virus-positive women: incidence and
      treatment dilemmas.
AB  - The increasing demand for fertility advice among human immunodeficiency virus
      (HIV)-positive women under our care led us to review the incidence of infertility
      and the ethical problems associated with its management. All HIV-positive women
      who attended the HIV outpatients clinic from October 1990 to the end of January
      1996 were studied. The main outcome measures were: the number of women undergoing
      infertility investigations before and after HIV diagnosis, their demographic and
      social details, and the outcome of these investigations. Most of the 183 women
      studied were in their reproductive years (mean age 32.7 +/- 6.7 years). Nine
      women had undergone infertility investigations, and/or treatment before HIV
      diagnosis, three of whom were diagnosed with HIV during routine testing prior to
      IVF treatment. Six declined further infertility treatment after discovering their
      HIV status. Eight women have undergone infertility investigations after HIV
      diagnosis but none have achieved pregnancy to date. Management decisions may have
      been hampered by ethical uncertainties in several cases. In conclusion therefore,
      as requests for infertility treatment from HIV-infected women occur and may
      become more common as the prevalence of HIV infection in women continues to rise,
      the ethical issues associated with the management of this problem demand urgent
      attention so that clear guidelines are available to aid treatment decisions.

PMID- 9021394
TI  - Endometrial stromal sarcoma diagnosed by operative hysteroscopy.
AB  - A 33 year old, para-2 woman had a 'submucous myoma' diagnosed in the uterine
      fundus during a diagnostic hysteroscopy because of dysfunctional bleeding. After
      pretreatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months,
      the myoma was resected through a resectoscope. Histological examination showed
      features of low-grade stromal sarcoma although no complete diagnostic certainty
      was reached. Due to the age of the patient and her wish to preserve fertility, it
      was decided not to perform extensive surgery but to perform hysteroscopy again in
      a follow-up visit after 3 months. Since the myoma had by this time recurred in
      the same place, it was decided to perform a total abdominal hysterectomy. The
      subsequent histopathological examination confirmed the growth of a low-grade
      stromal sarcoma. Following this diagnosis, the ovaries were removed
      laparoscopically and were found to be free of tumour.

PMID- 9021396
TI  - Sex selection experiments on man and other mammals.

PMID- 9021397
TI  - Infertile male patients are patients, not numbers.

PMID- 9021395
TI  - The application of positron emission tomography to the study of the normal
      menstrual cycle.
AB  - Positron emission tomography (PET) was used to investigate regions of the brain
      that are selectively affected during different phases of the normal menstrual
      cycle. A total of 10 healthy 18-29 year old female volunteers had PET
      measurements of brain glucose metabolism between days 5 and 9 of the follicular
      phase when plasma concentrations of oestradiol and progesterone were relatively
      low and between days 5 and 8 of the luteal phase when plasma concentrations of
      oestradiol and progesterone were relatively high. Automated algorithms were used
      to align the PET images in each individual, transform them into the coordinates
      of a brain atlas, control for variations in whole brain measurements and compute
      t-score maps of phase-related differences in regional glucose metabolism. The mid
      follicular phase was associated with significantly higher glucose metabolism in
      thalamic, prefrontal, temporoparietal and inferior temporal regions. The mid
      luteal phase was associated with significantly higher glucose metabolism in
      superior temporal, anterior temporal, occipital, cerebellar, cingulate and
      anterior insular regions. While this study should be considered to be
      exploratory, it provides normative data for future studies and illustrates how
      PET can be used to help characterize relationships between phases of the female
      life cycle, temporally related disorders and local functions of the living human
      brain.

PMID- 9021398
TI  - Staining of undecondensed sperm nucleii.

PMID- 9021399
TI  - In situ detection of tandem DNA repeat length.
AB  - A simple method for scoring short tandem DNA repeats is presented. An
      oligonucleotide target, containing tandem repeats embedded in a unique sequence,
      was hybridized to a set of complementary probes, containing tandem repeats known
      lengths. Single-stranded loops structures formed on duplexes containing a
      mismatched (different) number of tandem repeats. No loop structure formed on
      duplexes containing a matched (identical) number of tandem repeats. The matched
      and mismatched loop structures were enzymatically distinguished and
      differentially labeled by treatment with S1 nuclease and the Klenow fragment of
      DNA polymerase.

PMID- 9021400
TI  - Hinf I/Tsp509 I and BsoF I polymorphisms in the flanking regions of the human
      VNTR locus D1S80.
AB  - The minisatellite locus D1S80 (1p35-p36), is a highly polymorphic VNTR that also
      contains a Hinf I polymorphism in the 5' flanking region. Our data suggest that
      the Hinf I polymorphism is a G > T transversion 58 bases downstream from the
      forward primer. This G > T transversion also creates a Tsp509 I restriction site.
      Additionally, a G > C transversion polymorphism was identified in the 3' flanking
      region by the creation of a BsoF I restriction site immediately adjacent to the
      repeat region.

PMID- 9021401
TI  - Long range-inverse PCR (LR-IPCR): extending the useful range of inverse PCR.
AB  - The inverse PCR technique (IPCR) has proven to be very useful for the
      amplification of uncharacterized stretches of DNA upstream or downstream of
      regions that have already been cloned and sequenced. In practice, however,
      chromosome walking using standard IPCR is often a slow, repetitive process
      because only small DNA fragments are effectively amplified. The development of
      long and accurate PCR methodology has greatly expanded the range of DNA fragment
      sizes that is amenable to amplification by conventional PCR. We reasoned that
      combining long range PCR with IPCR would also extend the useful range of the IPCR
      technique. In this paper we demonstrate the utility of the hybrid, long range
      inverse PCR (LR-IPCR) technique by generating clones containing long stretches of
      DNA flanking endogenous chicken proviral elements.

PMID- 9021402
TI  - The application of microwave denaturation in comparative genomic hybridization.
AB  - Comparative genomic hybridization (CGH) is a powerful tool for analyzing
      unbalanced chromosomal rearrangements in a variety of tissues. However,
      reproducibility of the technique is poor. We have developed an alternative
      protocol involving microwave denaturation of the metaphase chromosome
      preparations prior to the hybridization step. The advantage of this method for
      CGH is the retention of the morphology of the chromosomes and hence an improved
      chromosome banding pattern. Furthermore, it results in a consistently strong
      hybridization which is not dependent on the batch of lymphocytes used to obtain
      the metaphase chromosome spreads. This procedure has also proved to be applicable
      to nucleic acid hybridizations in general. The protocol, its application and the
      results of this method in CGH is discussed. Furthermore preliminary results of
      this method in paint and DNA probe hybridizations to chromosome spreads and to
      RNA in tissue sections are presented.

PMID- 9021403
TI  - Detection of species-specific genetic markers in farm animals through random
      amplified polymorphic DNA (RAPD).
AB  - The potential use of random amplified polymorphic DNA (RAPD) was evaluated as a
      source of development of alternative genetic markers for studying variation in
      buffalo (Bubalus bubalis) and other related species of the Artiodactyla family
      Bovidae, in order to ascertain genetic relationships and diversities. Fourteen
      arbitrary primers were used to amplify DNA fragments in four species such as
      Indian Zebu cattle (Bos indicus), buffalo (Bubalus bubalis), sheep (Ovis aries)
      and goat (Capra hircus). Clear and distinct RAPD patterns with a higher level of
      polymorphism was detected between species, while fewer polymorphisms were found
      within the species. Species were subsequently scored for presence or absence of
      RAPD fragments and Jaccard's similarity coefficients were calculated to quantify
      the genetic divergence among the species. Wagner parsimony analysis of the RAPD
      data for 542 markers resulted in one most parsimonious tree which revealed very
      low similarity among the four species analysed.

PMID- 9021404
TI  - Killer cell inhibitory receptor interactions with HLA class I molecules:
      implications for alloreactivity and transplantation.
AB  - Human killer cell inhibitory receptors (KIR) are novel members of the
      immunoglobulin superfamily of cell surface glycoproteins, which are expressed by
      lymphocytes with natural killers (NK) and cytotoxic T-cell (CTL) phenotypes.
      These receptors have specificity for relatively conserved epitopes of HLA-A, -B,
      and -C class I antigens. Recent studies have identified KIR as being involved in
      the transmission of negative, inhibitory signaling events to the cytotoxic cell
      which prevent or diminish target cell lysis. KIR are thus likely to play an
      important role in the responses of alloreactive NK cells and CTL to allogeneic
      HLA antigens. In this article, we review the known structural and functional
      characteristics of KIR, suggest a possible mechanism for the transmission of
      intracellular negative signaling by these receptors, and discuss the relevance of
      KIR function and HLA specificity to the clinical transplantation of allogeneic
      tissues.

PMID- 9021405
TI  - Interaction between certain major histocompatibility complex class II and T-cell
      receptor V beta alleles promotes the antibody production to extractable nuclear
      antigen-related peptides.
AB  - Our objective was to study the interaction between major histocompatibility
      complex (MHC) class II and T-cell receptor (TCR) alleles in the recognition of
      extractable nuclear antigen-derived peptides in 32 patients with systemic lupus
      erythematosus and 173 of their family members. MHC genes were analyzed using
      sequence specific oligonucleotides, and TCR beta-chain gene polymorphism using
      restriction fragment-length polymorphism. One dominant peptide (as defined by
      enzyme-linked immunosorbent assay autoantibody reactivity) was identified in each
      antigen studied: peptide 1-20 in Sm-D, peptide 35-58 in U1-RNP-A, and peptide 304
      324 in the Ro/SSA 60 Kd protein. None of the MHC class II and TCR beta haplotypes
      was directly associated with any of the autoantibodies. Twenty-six subjects had
      antibodies to the peptide Sm-D1-20; nine of them were DRB1*0101/DQB1*0501. Among
      subjects with this haplotype, the number of responders was higher (p < 0.028, p
      corrected, pc = 0.336) in those with the 2-25-9 TCR beta haplotype than in the
      remainder. Conversely, the number of DRB1*04/DQB1*0302 responders was lower (p <
      0.030, pc = 0.360) among subjects with the 23-20-9 TCR beta haplotype than in
      those without. The odds ratios (OR) were 4.23 and 0.21, respectively. Of the 54
      subjects positive for anti-U1-RNP-A 35-38, 13 were DRB1*0101/DQB1*0501 and eight
      DRB1*04/DQB1*0302. The percentage of responders was higher (p < 0.041, pc =
      0.492, OR = 3.48) in the former group of subjects with the 2-25-9 TCR beta
      haplotype, and lower (p < 0.02, pc = 0.024, OR = 0.09) in the latter with the 23
      20-9 TCR beta haplotype. Three of the 12 anti Ro/SSA 60Kd 304-324-positive
      subjects were DRB1*0101/DQB1*0501. All had the 2-25-9 TCR beta haplotype (p <
      0.046, pc = 0.552, OR = 6.29) and none the 23-20-9 (p < 0.031, pc = 0.372, OR =
      0.10). The same combinations of genes were associated with high/low response
      toward the three peptides. These data provide evidence for an interplay of the
      MHC class II and TCR beta alleles in the control of specific autoantibody
      response to well-defined nuclear Ag peptides.

PMID- 9021406
TI  - Augmentation of immune response by an analog of the antigenic peptide in a human
      T-cell clone recognizing mutated Ras-derived peptides.
AB  - T-cells that recognize mutated p21 Ras are relevant to immune surveillance
      systems against cancer. We report here evidence that immune responses of a T-cell
      clone recognizing mutated p21 Ras can be augmented by an analog peptide. Using
      spleen cells from a gastric cancer patient, we established the CD4+ alpha beta
      Th1-like clone C27 that recognizes wild-type (3EYKLVVVGAGGVGKS17) and mutated p21
      Ras protein molecules and peptides, in an HLA-DR1-restricted manner. C27
      responded prominently to mutated Ras peptides carrying Val or Ala at position 12,
      as compared to wild-type and other mutated peptides. C27 also exhibited a much
      stronger response to a mutated p21 Ras whole-protein molecule-carrying Val at
      position 12, as compared with the wild-type protein. The proliferative response
      and production of GM-CSF, TNF-alpha, and IFN-gamma by C27 were further augmented
      by replacing the possible first DR anchor 4Tyr of the mutated Ras peptide with
      Trp, a more potent anchor residue for the DR1 molecule. Enhancement of peptide
      antigenicity by substituting the HLA anchor residue of an antigenic peptide
      recognized by tumor-reactive T-cells may prove to be a novel strategy for antigen
      specific cancer immunotherapy.

PMID- 9021407
TI  - Population genetic studies of HLA-E: evidence for selection.
AB  - HLA-E is a nonclassical, class I gene (Ib) of unknown function. The study was
      initiated to determine the amount and nature of the variation in the class Ib
      gene HLA-E in diverse ethnic groups. A single base-pair substitution (A-->G at
      382, exon 3) resulting in a change from an arginine (R) to a glycine (G) at codon
      107 was found. A glycine was present at position 107 in individuals from four ape
      species, suggesting that EG107 is the older of the two alleles. The two human
      alleles were present in all samples studied. The alleles were in linkage
      disequilibrium with HLA-A (W = 0.58), HLA-B (W = 0.59) and HLA-C (W = 0.55) in
      the Hutterites. The frequencies of the two HLA-E alleles were more equal than
      expectations based on neutrality in inbred and outbred Caucasian samples
      (Watterson's F = 0.506, p = 0.02 and F = 0.512, p = 0.047, respectively) and
      nearly significant in African-American and Hispanic samples (F = 0.513, p = 0.063
      and F = 0.508, p = 0.053). These data suggest that this polymorphism arose before
      the expansion of Homo sapiens and has been maintained in diverse populations by
      stabilizing selection.

PMID- 9021408
TI  - HLA-G gene transcriptional regulation in trophoblasts and blood cells:
      differential binding of nuclear factors to a regulatory element located 1.1 kb
      from exon 1.
AB  - The HLA-G antigen is specifically expressed on trophoblasts at the maternal-fetal
      interface, while expression of classical class I HLA-A, -B, -C products is
      repressed in this tissue. The transcriptional level of the HLA-G gene is high in
      trophoblast cells and in JEG-3 choriocarcinoma cells, is markedly reduced in
      blood cells, and is shown here to be undetectable in the YT2C2 NK cell line. In
      an attempt to understand molecular mechanisms controlling cell-specific
      transcriptional regulation of the HLA-G gene in these cells, we focused our study
      on protein interaction with a 244-bp region located over 1.1 kb from exon 1,
      which has been shown to direct HLA-G expression in transgenic mouse trophoblast.
      Three specific complexes were detected, two of which are found exclusively in
      cells showing HLA-G transcriptional activity. The YT2C2 nuclear extracts contain
      restricted DNA-binding activity of an additional factor which could correlate
      with repression of HLA-G transcription in these cells.

PMID- 9021409
TI  - Differential binding of peptides substituted at putative C-terminal anchor
      residue to HLA-DQ8 and DQ9 differing only at beta 57.
AB  - HLA-DQ8 (DQA1*0302-DQB1*0302: DQ beta 57 Ala) and (DQA1*0302-DQB1*0303: DQ beta
      57 Asp) differ only at beta 57, at which polymorphism reportedly confers distinct
      susceptibility to insulin-dependent diabetes mellitus (IDDM). To identify the
      differential peptide binding affected by beta 57, we determined DQ9-binding
      peptides by affinity-based selection of a phage random peptide library using the
      biotinylated DQ9 complex. Nonconservative single-residue substitution of high
      affinity DQ8- and DQ9-binding peptide (1KLPDYVLWSSSTVVGLGAAGA21) at the
      underlined residues significantly decreased the peptide binding to DQ8 and DQ9.
      Affinities of the wild-type 21-mer K4DYVLWSSSTV13 and K4AYAAWAAATA13 to DQ8 and
      DQ9 were practically the same. The K4DYVLWSSSTV13-based analogue peptides with
      substitutions at 12T showed that residues R, K, H, E, D, Q, N, T, S, V, L, I, F,
      M, W, and Y permitted binding to DQ8, whereas only R, T, V, L, I, F, M, W, and Y
      did so to DQ9. Thus, significant differences exist between DQ9 and DQ8, in that
      the majority of polar residues, regardless of their static charges at the residue
      12, permitted binding to IDDM-susceptible DQ8, which is not the case for DQ9. The
      affinities of K4DYVLWSSSXV13 AND K4AYAAWAAAAX13 (where X is T, A, K, D, or I)
      were almost equal to DQ8 and DQ9, suggesting the DQ8- and DQ9-binding peptide
      motifs could accept both the 8-mer and 9-mer frames depending on intervening
      sequences between N- and C-terminal anchor residues. The biochemical basis of
      peptide-HLA interactions determined by DQ beta 57 is discussed.

PMID- 9021410
TI  - HLA gene haplotype frequencies in bone marrow donors worldwide registries.
AB  - To calculate reliable HLA gene and haplotype frequencies of bone marrow donors in
      various regions in the world, we have analyzed the HLA-A, -B, and -DR phenotype
      frequencies of 18 bone marrow donor registries with a total of more than 300,000
      HLA-A, -B-typed donors. These registries were included in the 22nd edition of
      Bone Marrow Donors Worldwide. Maximum likelihood gene frequencies, Hardy-Weinberg
      equilibrium fit, and 2- and 3-locus haplotype frequencies were calculated as well
      as deltas, relative deltas, and their significance. Remarkable gene and haplotype
      frequency differences exist between the registries. The genetic distances between
      the different registries were used to draw phylogenetic trees that clearly show
      that the degree of similarity between registries is related to their geographic
      locations. The resulting frequencies can be used for the estimation of the
      probability of finding a hyplotypically identical related or unrelated bone
      marrow donor for an individual patient. Phylogenetic trees are useful
      representations of the similarity between donor pools and can also aid in the
      selection of donors.

PMID- 9021411
TI  - Nomenclature for factors of the HLA system, update July 1996. The WHO
      Nomenclature Committee for factors of the HLA system.

PMID- 9021412
TI  - Retooling for community health partnerships in primary care and prevention.

PMID- 9021413
TI  - Adult adjustment to chronic illness: a review of the literature.
AB  - The uncertain nature and erratic course of chronic illnesses pose unique
      challenges for those diagnosed. To help the growing numbers of nongeriatric
      adults clients with chronic illness, social workers are obliged to develop a
      substantial awareness surrounding the topic. An assessment of each client's
      developmental needs and an understanding of how that individual copes with
      emotional loss are critical to providing psychosocial assistance most
      effectively. This article surveys the current professional literature regarding
      adjustment to chronic illness and addresses its significance and implications for
      social workers.

PMID- 9021414
TI  - The value and use of the Qualified Medicare Beneficiary Program: early evidence
      from Tennessee.
AB  - The Qualified Medicare Beneficiary (QMB) Program eliminated the out-of-pocket
      costs of obtaining health care services under the Medicare program for some low
      income beneficiaries who were previously ineligible for Medicaid. The program is
      underused, and little is known about its effects. The article describes the QMB
      Program and compares program beneficiaries with others whose out-of-pocket
      payments are covered by Medicaid. Using Medicare claims data covering QMBs in
      Tennessee, we found that the program financed a relatively high rate of use of
      Medicare services and saved low-income Medicare beneficiaries hundreds of dollars
      per month in out-of-pocket costs. Social workers can promote the program and
      increase the use of its covered services appropriately, thereby by maximizing its
      potential benefits to low-income people.

PMID- 9021415
TI  - The case for integration of social work psychosocial services into rural primary
      care practice.
AB  - This article argues for health and mental health collaboration between social
      workers and rural primary care physicians and describes a study of physicians'
      attitudes toward integrated services. The physicians who expressed interest in a
      collaborative arrangement differed in practice characteristics, attitudes toward
      social workers, and endorsement of social work roles. Also, interested physicians
      treated significantly more patients, had the lowest proportion of patients over
      age 65, and endorsed as useful a significantly larger number of social work
      activities. If social workers aspire to collaborative arrangements in rural
      primary care, they must provide excellent services now, continue to work toward a
      better understanding of their broad mental health competencies, and be willing to
      provide services that conform to the expectations and limitations of primary
      care.

PMID- 9021416
TI  - A comprehensive Afrocentric rites of passage program for black male adolescents.
AB  - The health consequences for African American male teenagers of living in high
      risk environments are devastating. Given the existence of cultural barriers to
      health services use, culturally proficient programs that can engage African
      American male youths in preventive interventions and primary care are urgently
      needed. This article reviews the health status of African American male
      adolescents, noting that the leading health problems are preventable. The article
      then discusses two frameworks that are of value in social work practice with
      African American populations, cultural competence and empowerment; reviews of
      Afrocentric theory and Afrocentric social work; and describes a culturally
      proficient, Afrocentric program for African American male adolescents. Health
      social workers can take steps to increase their own cultural competence and that
      of the health care organizations in which they work.

PMID- 9021417
TI  - Engaging and retaining women in outpatient alcohol and other drug treatment: the
      effect of referral intensity.
AB  - Women with alcohol or other drug (AOD) problems experience a range of barriers to
      inpatient treatment. Although research in the general population shows that high
      intensity referrals are more effective than low-intensity referrals at engaging
      and retaining individuals in outpatient AOD treatment, the impact of referral
      intensity has not been assessed for women only. To examine this issue, a
      secondary analysis was conducted using an existing data set that included a
      sample of 109 women. Although intensity of referral was not related to entry into
      or relapse during treatment, high-intensity referral was associated with
      completion of treatment. In addition, women who relapsed during treatment were
      less likely to complete it, underscoring the need for relapse prevention
      training.

PMID- 9021418
TI  - Women living with HIV/AIDS: the dual challenge of being a patient and caregiver.
AB  - More than 60,000 women in the United States have been diagnosed with AIDS, and
      millions of women worldwide are infected with HIV. Most of these women will die
      at an early age, leaving their children motherless. During their HIV illness,
      women confront the challenge of being both patient and family caregiver. Little
      research has explored this dual challenge. The authors conducted semistructured
      one-hour interviews with HIV-positive women that focused on the impact of the HIV
      diagnosis on the women's lives. Significant factors emerging from the interviews
      included the impact of stigma associated with HIV/AIDS, disbelief of the
      diagnosis, the lack of a guardian for their children, the paucity of women's
      support groups, and barriers associated with seeking services. All women
      exhibited evidence of clinical depression. A model for multidisciplinary
      intervention is proposed that focuses on women's needs within their family
      systems.

PMID- 9021420
TI  - Of magic bullets and social justice: emerging challenges of recent advances in
      AIDS treatment.

PMID- 9021419
TI  - Addressing at-risk pregnant women's issues through community, individual and
      corporate grassroots efforts.

PMID- 9021421
TI  - We need to monitor changes.

PMID- 9021422
TI  - Detection of embolic signals using Doppler ultrasound: a new approach to cardiac
      embolism.
AB  - Cerebral embolism from cardiac, aortic or carotid cause can be detected by
      Doppler examination of carotid arteries or transcranial Doppler with long
      duration recordings. The signals detected called HITS (high intensity transient
      signals), which have been described in vitro and in vivo, have specific physical
      characteristics. This novel technique is considered promising in establishing the
      relationship between the discovery of embolic heart disease and its clinical
      neurological manifestations. In the evaluation of a stroke, the detection of HITS
      could provide evidence in support of an embolic cause. The areas of application
      of this new technique are many: screening for asymptomatic embolism in patients
      with an embolic cardiac disorder, and effects of antiplatelet and anticoagulant
      medications or surgical treatments.

PMID- 9021423
TI  - Right ventricular function before and after percutaneous balloon mitral
      valvuloplasty.
AB  - Aim of this study was to evaluate right ventricular performance in patients with
      mitral stenosis and its modification by balloon valvuloplasty. Right ventricular
      volumes of 24 patients with postrheumatic mitral stenosis were determined by
      thermodilution 1 or 2 days before and 1 or 2 days after valvuloplasty. Right
      ventricular ejection fraction at rest was 43 (36-47)% (median and interquartile
      range). Right ventricular end-diastolic volume was 100 (86-119) ml/m2. Supine
      bicycle exercise (50 Watt) reduced right ventricular ejection fraction to 30 (29
      37)% (P < 0.0001) and increased right ventricular end-diastolic volume to 124
      (112-141) ml/m2 (P < 0.0001). At rest, right ventricular ejection fraction
      correlated inversely with pulmonary vascular resistance (r = -0.64, P < 0.0001),
      while no significant correlation with mitral valve area was found. Valvuloplasty
      increased right ventricular ejection fraction at rest to 48 (44-50)% (P < 0.005),
      and during exercise to 42 (38-45)% (P < 0.0001). This improvement of right
      ventricular ejection fraction correlated inversely with the value of this
      parameter before valvuloplasty (r = -0.88, P < 0.0001) and with the gain in
      stroke volume (r = 0.57, P < 0.01). The right ventricular function curve,
      disturbed before commissurotomy, was reestablished by the procedure. In
      conclusion, at the here investigated stage of mitral stenosis right ventricular
      function is reversibly impaired. This is predominantly caused by the hemodynamic
      consequences of the valvular defect and not by an impairment of right ventricular
      myocardial function.

PMID- 9021424
TI  - Cardiorespiratory responses to exercise after repair of the univentricular heart.
AB  - The purpose of this study is to evaluate cardiorespiratory responses to exercise
      in patients with univentricular heart according to the type of repair used. Forty
      three patients with univentricular heart were divided into three groups: 15
      preoperative patients (group A), 18 who had Fontan repair (group B) and 10 who
      had ventricular septation (group C). Group C was further divided into two
      subgroups, 7 with normal atrioventricular valve function (group C1) and 3 with
      atrioventricular valve regurgitation (group C2). Cardiorespiratory variables were
      determined after performance of cardiopulmonary exercise testing. One-hundred-and
      twenty-five healthy subjects, age 5-26 years, served as controls. Oxygen uptake
      in group C1 at both ventilatory threshold and peak exercise was highest in all
      groups of univentricular heart (P < 0.05), while peak oxygen uptake in group C1
      was significantly lower vs controls (P < 0.001), and that in group B was
      significantly higher than that for group A. Although chronotropic incompetence
      was noted in all groups of univentricular heart, marked improvements in both the
      relationship between heart rate and oxygen uptake and in the ventilatory
      efficiency were observed after definitive repair. While ventilatory efficiency
      was still impaired in group B, there was no significant difference between that
      in group C1 and the control group. When patients with univentricular heart of the
      left ventricular type (Van Praagh's type A single ventricle) were analyzed
      separately, superior cardiorespiratory response after ventricular septation was
      also found. In view of these findings, the ventricular septation procedure is
      preferred to the Fontan method in patients with univentricular heart when
      morphological conditions are suitable for this procedure so as not to make
      residual complications, such as significant atrioventricular valve regurgitation.

PMID- 9021425
TI  - Arterial remodeling after experimental percutaneous injury is highly dependent on
      adventitial injury and histopathology.
AB  - BACKGROUND: The extent and nature of unfavorable geometric remodeling, especially
      related to the adventitia, has not been studied previously. The purpose of this
      study was to examine two methods of experimental arterial injury, characterize
      the extent of remodeling, and determine if remodeling is injury-specific.
      METHODS: Two methods for producing coronary stenoses in pigs were used: heat
      injury using thermal balloon angioplasty (resulting in adventitial fibrosis), and
      copper stent implantation (resulting in intense inflammation). Histomorphometric
      parameters included changes in neointimal thickness (delta neointima) from
      uninjured to injured sections, and differences in area circumscribed by the
      internal and external elastic laminas (delta internal elastic lamina area and
      delta external elastic lamina area, respectively). Remodeling was calculated for
      each lesion as the enlargement of the external elastic lamina area or internal
      elastic lamina area for incremental neointimal thickening, expressed as the
      slopes delta external elastic area/delta neointima and delta internal elastic
      lamina area/delta neointima. RESULTS: Remodeling indices for the heat lesions for
      the heat lesions were negative (delta internal elastic lamina area/delta
      neointima = 0.15, delta external elastic lamina area/delta neointima = 0.64) and
      indicated little remodeling in contrast to copper stent injury (delta internal
      elastic lamina area/delta neointima = 0.95, delta external elastic lamina
      area/delta neointima = 1.20). CONCLUSIONS: Remodeling in fibrotic compared to
      inflammatory lesions differs markedly, and may explain increased restenosis rates
      observed in thermal balloon angioplasty in patients. This formulation may be
      useful to study remodeling and restenosis following interventional technologies.

PMID- 9021426
TI  - Mild mitral regurgitation reduces exercise capacity in patients with idiopathic
      dilated cardiomyopathy.
AB  - We evaluated 30 patients with dilated cardiomyopathy (New York Heart Association
      functional Class II or III with medical treatment) to assess the effect of mild
      mitral regurgitation (MR) on exercise capacity in patients with congestive heart
      failure. They were classified into two groups based on results of left
      ventriculography: MR present (n = 10) and MR absent (n = 20). The severity of the
      MR by left ventriculography was grade I (mild) in all patients with MR. Steady
      state hemodynamic data and angiographic data did not differ significantly between
      the two groups. Heart rate and systolic blood pressure at rest and in response to
      symptom-limited exercise testing did not differ between the groups. However, the
      peak work load was significantly lower in the group with MR than that in the
      group without MR (101 +/- 32 vs. 142 +/- 29 W, respectively; p < 0.005). Peak
      oxygen uptake and peak oxygen pulse were also significantly lower in the group
      with MR than in that without MR (peak oxygen uptake: 18 +/- 23 +/- 5 ml/min/kg; p
      < 0.05, peak oxygen pulse: 6.6 +/- 2.6 vs. 9.5 +/- 2.7 ml/min/beat: p < 0.01,
      respectively). Thus, mild MR had a detrimental effect on the exercise capacity in
      patients with dilated cardiomyopathy.

PMID- 9021427
TI  - Coronary artery fistula in children and adults: a review of 25 cases with long
      term observations.
AB  - We studied 25 patients with coronary artery fistula between 1976 and 1994. Age
      ranged from 1 to 58 years. Twelve patients were symptomatic; seven had dyspnoea,
      four had angina, one had palpitation and one had syncope. Coronary arteries in
      four. Coronary artery fistula drained into right ventricle in 11, right atrium in
      nine, pulmonary artery in four and left ventricle in two. The Qp/Qs ranged from
      1.0 to 2.6 with a mean of 1.39 +/- 0.38. Five patients had associated cardiac
      anomalies. Two had atrial septal defects, one had patent ductus arteriosus, one
      had atresia of proximal right coronary artery and in one patient, the right
      coronary was arising from left coronary artery. Five patients underwent surgery
      without any operative mortality. Thirteen patients were followed-up medically for
      a mean period of 6.1 +/- 5.1 years. There were no complications related to
      coronary artery fistula during follow-up. In one patient coronary artery fistula
      closed spontaneously.

PMID- 9021428
TI  - Conversion of recent onset atrial fibrillation to sinus rhythm using a single
      oral loading dose of propafenone: comparison of two regimens.
AB  - A population of 105 patients with recent onset (< 72 h) atrial fibrillation was
      randomly treated with propafenone as a single oral loading dose of 450 mg
      (Regimen A) or 600 mg (Regimen B) or with placebo. A 24-h Holter was performed.
      Criteria of efficacy were conversion to sinus rhythm at 2, 4 and 8 h compared to
      placebo and also significant reduction of mean ventricular rate in persistent
      atrial fibrillation. After 2 h, regimen B was more effective than either regimen
      A (43% vs. 8%; p = 0.001) or placebo (11%; p = 0.004). At 4 h, both the active
      treatments were more effective than placebo (17% vs. 46% regimen A and 57% vs.
      regimen B; p < 0.04 and p < 0.001, respectively). Sinus rhythm resumed within 24
      h in 71%, 80% and 69% of the patients with regimen A, B and placebo, respectively
      (p = not significant). The mean ventricular rate reduction after 1 h was 8%, 11%
      and 4% for regimen A, B and placebo, respectively (p < 0.005 vs. regimen B), and
      17%, 25% and 6% respectively (p < 0.001 placebo vs. regimen A and B, p < 0.05
      regimen B vs. A) at 2 h. No major adverse effect occurred. Atrial flutter with
      1:1 atrioventricular conduction only in one case who received placebo.
      Propafenone acute oral administration is more effective than placebo in rapidly
      converting recent-onset atrial fibrillation to sinus rhythm and may be the
      treatment of choice in this setting limiting hospitalization and contributing to
      improved quality of life.

PMID- 9021429
TI  - Association of higher saturated fat intake with higher risk of hypertension in an
      urban population of Trivandrum in south India.
AB  - Saturated fat intake appears to be a risk factor of insulin resistance which is
      important in the pathogenesis of diabetes and cardiovascular disease. This study
      aims to demonstrate whether saturated fat intake may be a risk factor of
      hypertension. Cross-sectional survey in six randomly selected streets in
      Trivandrum city in south India was conducted to study 1497 randomly selected
      subjects (737 males and 760 females) of 25-64 years of age. The prevalence of
      hypertension by Joint National Committee V criteria (> 140/90 were 34.6% (n =
      255) in males and 30.7% (n = 234) in females. The consumption of food groups
      showed that they were within desirable limits. However, the intake of fruit,
      vegetable, legume and coconuts was lower and saturated fat intake higher (> 10%
      kcal/day), although total fat intake was within desirable limits. Total and
      saturated fat intake, and the consumption of coconut oil and butter, flesh foods,
      milk and yogurt as well as sugar and jaggery were significantly associated with
      hypertension. Total visible fat (> 20 g/day) intake was positively associated
      whereas fruit, vegetable, legume and coconut intake (< 400 g/day) was inversely
      associated with hypertension. Salt intake (> 8 g/day), smoking and illiteracy
      were not associated with hypertension. Multivariate logistic regression analysis
      showed that saturated fat intake, age and body mass index were independently and
      strongly associated with hypertension whereas fruits, vegetable, legume and
      coconuts, coconut oil and butter and alcohol (males) intakes were weakly
      associated with hypertension. The odds ratio indicate higher risk of hypertension
      due to higher intake of saturated fat in both sexes (mean: odds ratio, 1.07, 95%
      confidence interval 1.05-1.09; women, 1.08, 1.06-1.12, P < 0.01). Significant
      determinants of hypertension were higher saturated fat, particularly coconut oil,
      and lower fruit, vegetable, legume and coconuts, particularly legumes and
      coconuts in the diet, apart from conventional risk factors.

PMID- 9021430
TI  - Haemodynamic changes during dobutamine stress echocardiography in patients with
      and without ischaemia.
AB  - We studied haemodynamic changes during dobutamine stress echocardiography in 69
      patients (mean age 58 years, 6 female, 63 male) referred for investigation of
      chest pain. We used a standard protocol of 3 min stages using infusion rates of
      5, 10, 20, 30 and 40 micrograms/kg/min. Heart rate rose from 74 (13) to 123 (21)
      beats per min with the major increment occurring during the high dose phase of
      the study (> 20 micrograms/kg/min). Stroke volume was calculated as the product
      of left ventricular outflow tract cross-sectional area and the velocity integral
      of the continuous wave aortic signal. Mean stroke volume increased from 67.5 (22)
      ml pre-test to 82 (22) ml at 20 micrograms/kg/min dose (P < 0.0001) and 85 (21)
      ml at 40 micrograms/kg/min (P < 0.00001). Only 15 patients (26%) reached their
      maximal stroke volume by 10 micrograms/kg/min, 38 patients (65%) reached maximal
      stroke volume by 20 micrograms/kg/min. Patients with ischaemic responses tended
      to have a blunted rise in stroke volume from 67 (22) ml to 85 (22) ml at maximum
      compared with a rise from 69 (23) to 92 (19) ml in those without ischaemic (P =
      0.09). In conclusion, the early rise in cardiac output during dobutamine stress
      was mainly due to a rise in stroke volume and the later due to an increase in
      heart rate. Individual increases in stroke volume did not adequately
      differentiate between ischaemic and non-ischaemic results.

PMID- 9021431
TI  - Clinical epidemiology of acute myocardial infarction in Sharjah, United Arab
      Emirates.
AB  - Little published information about the clinical epidemiology of acute myocardial
      infarction (AMI) in the United Arab Emirates (UAE) is available. To fill this
      knowledge gap, all patients with confirmed AMI who were treated at the intensive
      care unit of the Kuwait Hospital, Sharjah, during 1991 were prospectively
      studied. This hospital, primarily for expatriate patients, provides outpatient
      and hospital care to expatriates for a nominal fee and to UAE citizens free of
      charge. It is estimated that about 80% of all expatriate AMI patients in Sharjah
      receive initial treatment at this hospital. Of all 153 were recorded in 30.2
      (39/129), 17.8 (27/152) and 14.6% (22/151) of the patients, respectively.
      Overall, 73.7% (112/152) of the patients were current cigarette smokers. Of all
      153 patients, 48.4, 35.9, 7.2 and 8.5% had anterior, inferior, lateral and
      'other' types of AMI, respectively. Of 152 patients with available data, 15
      (9.9%) died in the hospital. In a multivariate logistic regression model
      including all significant univariate correlates of in-hospital death (age,
      nationality, history of hypertension and current smoking practice) as independent
      variables, only being a current cigarette smoker was significantly related to a
      lower risk of in-hospital death in the study patients (O.R. = 0.27; 95% C.I.:
      0.08-0.96). Also, UAE Arab nationality and preexisting hypertension were notable,
      though nonsignificant, positive correlates of in-hospital death in this model.
      These finding should guide future in-depth studies of the clinical epidemiology
      of AMI in Sharjah and elsewhere in the UAE.

PMID- 9021432
TI  - Use of low molecular weight heparin in postangioplasty management.
AB  - The results of using low molecular weight heparin (LMWH) in postangioplasty
      management are examined. In comparison to intravenous unfractionated heparin,
      subcutaneous LMWH caused less groin complications and was simpler and cheaper to
      be administered by the medical personnel. The incidence of ischaemic
      complications after angioplasty including acute closure and myocardial
      infarction, however, remained similar and was not excessive. Subcutaneous
      administration of LMWH provides and alternative simple and cost-effective
      strategy for postangioplasty management.

PMID- 9021433
TI  - Localized right atrial tamponade after cardiac surgery.

PMID- 9021434
TI  - Pharmacokinetics and pharmacodynamics of enantiomers of ibuprofen and
      flurbiprofen after oral administration.
AB  - The main objective of this study was to develop a pharmacokinetic-pharmacodynamic
      (PK/PD) model for the analgesic effect of ibuprofen and flurbiprofen using
      subjective as well as objective parameters. Serum concentrations of the
      individual enantiomers after oral administration of racemic ibuprofen (400 mg)
      and flurbiprofen (100 mg) were monitored using reversed phase HPLC. The
      pharmacokinetic data of the S-enantiomer was linked to the effect data using a
      hypothetical effect compartment. The effect data were fitted to Emax model. PK/PD
      analysis were performed using both objective (evoked potentials) and subjective
      (pain intensity scale) parameters. Concentrations of S-ibuprofen were found to be
      consistently larger than of R-ibuprofen and differed in various pharmacokinetic
      parameters after oral administration of racemic ibuprofen. Pharmacokinetic
      parameters of the enantiomers of flurbiprofen, such as volume of administration
      and clearance, also differed. Comparison of cumulative effects calculated as the
      area under the effect-time curve (AUCE) showed a statistically significant
      difference from placebo for both ibuprofen and flurbiprofen using evoked
      potential values. However, using pain rating values ibuprofen AUCE did not differ
      statistically significant from placebo whereas flurbiprofen AUCE did. PK/PD
      modeling of both evoked potentials and pain rating data than in evoked potential
      data. Hence, EP monitoring may allow to evaluate analgesic activity with a
      smaller number of subjects than pain rating.

PMID- 9021435
TI  - Pharmacokinetics and bioequivalence of the main metabolites of selegiline:
      desmethylselegiline, methamphetamine and amphetamine after oral administration of
      selegiline.
AB  - A bioavailability study of 2 different selegiline preparations were conducted in
      20 healthy volunteers to test the bioequivalence. Almost no bioavailability study
      of selegiline has been published. As plasma levels of selegiline are very low and
      the elimination half-life is very short being about 9 minutes, therefore, a very
      sensitive and selective method for determining the 3 main metabolites
      desmethylselegiline (DMS), methamphetamine (MA) and amphetamine (A) was
      developed. After application of a single oral dose of 5 mg selegiline the Cmax
      values of DMS reached 5-6 ng/ml, of MA 6-7 ng/ml and of A about 2 ng/ml. The AUC
      infinity values were with DMS about 11 ng/ml x h +/- 4.5, with MA about 130 g/ml
      x h +/- 50 and with A about 50 ng/ml x h +/- 15. The 90% confidence interval was
      with logarithmic transformed AUC infinity values 92-107% with DMS, 89-107% with
      MA, and 84-104% with A. The logarithmic transformed Cmax values showed a 90%
      confidence interval of 92-127% with DMS, 91-101% with MA, and 90-103% with A. All
      relevant pharmacokinetic parameters showed bioequivalence with all 3 metabolites
      (DMS, MA, and A).

PMID- 9021436
TI  - Urinary 6 beta-hydroxycortisol and D-glucaric acid excretion rates are not
      affected by lansoprazole treatment.
AB  - Lansoprazole has been shown to induce cytochrome P450 1A (CYP1A) and CYP3A
      enzymes in human hepatocytes in vitro. In this study, urinary excretion of 6 beta
      hydroxycortisol (6 beta-OHF) and D-glucaric acid (D-GA) were used to investigate
      the potential enzyme-inducing property of lansoprazole in vivo. Twenty-four
      healthy female volunteers (aged 19-35 years), who were taking oral contraceptives
      containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel, were randomized
      in a cross-over design for the treatment with either 60 mg lansoprazole or
      placebo once daily during 2 subsequent menstrual cycles. Urinary excretion rates
      of 6 beta-OHF and D-GA were measured at days 14 and 21 of the menstrual cycles.
      Median pretreatment urinary excretion of 6 beta-OHF (212 and 218 micrograms/d, n
      = 24) and D-GA (20.1 and 32.7 mumol/d) did not significantly differ. Upon
      treatment median excretion of 6 beta-OHF was 255 and 241 micrograms/d (n = 23),
      and that of D-GA was 25.5 and 33.8 mumol/d, respectively. Thus, the relatively
      high dose of 60 mg/d lansoprazole failed to statistically significantly alter
      urinary excretion of 6 beta-OHF and D-GA, indicating that therapeutic doses of
      lansoprazole might not exhibit a phenobarbital-like induction in vivo.

PMID- 9021437
TI  - Oral fenoterol versus sustained release theophylline in adult asthmatics.
AB  - AIM: The question regarding the minimal effective oral dose of fenoterol remains
      unanswered. The present study was undertaken to compare the therapeutic effects
      of sustained release theophylline and a conventional low dose oral fenoterol in
      patients with asthma. PATIENTS AND METHODS: A double-blind, double-dummy,
      randomized, 2-phase, cross-over comparison between sustained-release theophylline
      (SR-T) and oral fenoterol 2.5 mg 3 times daily in 21 patients with stable
      bronchial asthma (mean age 51 years) was conducted. Each drug was administered
      for a 2-week period. All patients qualified with a > or = 15% reversibility in
      forced expiratory volume in 1 second (FEV1) following 200 micrograms of inhaled
      salbutamol. Spirometric tests and body plethysmography were done at baseline and
      at the end of each treatment period. Blood was drawn for routine laboratory
      analysis and serum theophylline concentration. During each treatment period the
      patient kept a diary of symptoms and the concurrent use of inhaled salbutamol was
      recorded. RESULTS: During SR-T administration trough serum concentrations were
      12.9 (1.5) mg/l mean (+/- SEM). SR-theophylline produced greater maximal changes
      in all parameters measured: FEV1, forced vital capacity, and specific airway
      resistance from the pretreatment and fenoterol phase, while fenoterol caused
      significant changes in none of the test variables. Patients showed an overall
      preference for SR-T over fenoterol (p < 0.05). CONCLUSIONS: Thus, 2.5 mg of
      fenoterol at 8-hour intervals did not prove to be an effective alternative to
      sustained release theophylline for management of patients with asthma. An
      appropriate dosing schedule for fenoterol needs to be redefined.

PMID- 9021439
TI  - Pharmacokinetics of tirilazad in healthy male subjects at doses above 6
      mg/kg/day.
AB  - The dose proportionality of tirilazad pharmacokinetics at dosages above 6.0
      mg/kg/day were assessed in 18 healthy male volunteers between the ages of 19 and
      46 years. Subjects were randomized to receive either 1.5 mg/kg, 3.0 mg/kg, or 4.0
      mg/kg tirilazad mesylate every 6 hours for 29 doses (daily doses of 6.0, 12.0,
      and 16.0 mg/kg/day for 7 days). Each drug dose was administered intravenously
      over 10 minutes. Plasma tirilazad, U-89678, and U-87999 (active reduced
      metabolites) were quantified by HPLC. Two subjects in the high dose group
      withdrew before the end of the study. Following the first dose of tirilazad, dose
      corrected pharmacokinetic parameters for all 3 compounds did not differ
      significantly among dose groups. After the final tirilazad the mean half-life of
      tirilazad was approximately 80 hours. Mean apparent tirilazad clearance did not
      differ significantly among groups. Mean U-89678 AUC0-6 following the last
      tirilazad dose did not differ significantly between the 6.0 and 12.0 mg/kg/day
      doses, but the value for the 16.0 mg/kg dose was higher than values from both
      lower doses (p = 0.044 and 0.056, respectively). Similar results were obtained
      for U-87999. The dose effects observed for the pharmacokinetics of these 2
      metabolites may have been a function of intersubject variability. When combined
      with previous data concerning the dose proportionally of tirilazad
      pharmacokinetics at doses less than 6.0 mg/kg/day, the data from the present
      study suggest that the pharmacokinetics of tirilazad are approximately linear
      over a dosage range of 1.0-16.0 mg/kg/day. Due to the inability to assess the
      plasma protein binding of tirilazad and its reduced metabolites, the clinical
      significance of the departure from linearity of the pharmacokinetics of U-89678
      and U-87999 cannot be directly assessed. Further study at higher doses will be
      needed to address this issue.

PMID- 9021438
TI  - Population pharmacokinetics of amikacin in geriatric patients studied with the
      NPEM-2 algorithm.
AB  - The population pharmacokinetics of amikacin were studied in 40 geriatric medicine
      patients (aged 59-95 years, average 78 years) by the NPEM-2 algorithm, using a 2
      compartment model. The fitted parameters were: renal clearance of amikacin,
      expressed as a fraction of creatinine clearance (CLS) and volume of the central
      compartment, expressed as a fraction of body weight (VS). The nonrenal clearance
      of amikacin (CLi) and the transfer constants between the 2 compartments (k12 and
      k21) were held constant. The distribution of each pharmacokinetic parameter was
      characterized by the median and the 50% dispersion factor (DF50) which is the
      interval between the 25th and 75th percentiles, divided by 1.32. The parameters
      were thus estimated by the following values: CLs = 0.91 +/- 0.45 and Vs = 0.29 +/
      0.10 l x kg-1. The volume of distribution was increased with respect to the
      usual value of 0.20 l x kg-1. The interindividual variability was high,
      particularly for clearance. Although the median value of CLs was close to unity,
      indicating that for most patients the elimination kinetics of amikacin followed
      that of creatinine, there was a slight probability to observe much higher values
      of CLs (up to 5), indicating that for some aged patients the elimination of
      amikacin was less altered than that of creatinine. These parameters were used as
      reference population values to estimate the pharmacokinetics of amikacin in a
      second group of 20 patients by the Bayesian method, with 2 blood samples per
      patient. For each patient the fitted parameters were able to predict the plasma
      concentrations of amikacin during the next 72 hours with no significant bias and
      a precision of 3.5 mg x 1(-1). This study confirms the ability of the NPEM-2
      algorithm to provide reference population values for use in Bayesian monitoring
      of aminoglycoside therapy.

PMID- 9021440
TI  - Predicting glomerular function from adjusted serum creatinine in renal transplant
      patients.
AB  - In 22 individuals with a renal graft the correlations between the renal clearance
      of polyfructosan (CLPF), renal creatinine clearance (CLcr)--established under the
      same conditions as CLPF--and the value of glomerular function predicted using the
      equation by Cocroft and Gault (PredCLcr) were followed up, at an interval of 2-3
      months, for 8-22 months. A significant linear correlation (r = 0.777, p < 0.001)
      was found between PredCLcr and CLPF as well as between PredCLcr and CLcr (r =
      0.801, p < 0.001). Equally significant correlations, however, were established
      when relating the serum concentrations of creatinine (Scr) to 1/CLPF (r = 0.784,
      p < 0.001) and Scr to 1/CLcr (r = 0.744, p < 0.001). The values of the
      PredCLcr/CLPF and PredCLcr/CLcr ratios during follow-up in one and the same
      individual may vary significantly. This fluctuation exceeds maximal error of the
      analytical methods employed in one third of the individuals examined. When
      considering stabilization or slow changes in graft function on the basis of
      PredCLcr and CLPF we found significant discrepancies in more than one half of the
      individuals examined (64%). The findings support the assumption that more
      accurate methods must be used to assess graft glomerular function on long-term
      follow-up.

PMID- 9021441
TI  - Changes in plasma cardiac natriuretic peptides concentrations during 1 year
      treatment with angiotensin-converting enzyme inhibitor in elderly hypertensive
      patients with left ventricular hypertrophy.
AB  - Plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) are
      high in patients with hypertension and congestive heart failure. The present
      study examined changes in plasma ANP and BNP concentrations during 1 year of
      monotherapy with enalapril in elderly hypertensive patients with left ventricular
      (LV) hypertrophy. Eight elderly hypertensive patients with LV hypertrophy were
      treated with enalapril for 1 year, during which time serial changes were recorded
      in LV mass index, LV systolic function, and plasma concentrations of ANP and BNP.
      Enalapril maintained systolic and diastolic blood pressure in the normal range
      for over 1 year. Treatment significantly reduced posterior wall thickness at 6
      months, and more so at 1 year, and tended to reduce septal wall thickness and LV
      mass index at 1 year. LV ejection fraction was slightly but significantly
      increased at 1 year. Plasma ANP and BNP, which were markedly elevated at study
      entry, both decreased after 1 year of enalapril. These results suggest that 1
      year of treatment with enalapril caused both a modest regression of LV
      hypertrophy and a modest improvement in LV systolic function in our selected
      group of elderly hypertensive patients. The drug reduced elevated plasma ANP and
      BNP levels but did not alter BUN and serum creatinine levels. Enalapril appears
      to be useful for the treatment of elderly hypertensive patients with LV
      hypertrophy.

PMID- 9021442
TI  - Bioequivalence of tolbutamide-containing tablet preparations.
AB  - The present crossover study was undertaken to investigate in 22 volunteers (15
      males, 7 females, aged 22-28 years) whether the 2 tolbutamide preparations
      (tolbutamide R.A.N. vs. rastinon Hoechst) are bioequivalent. After administering
      a single dose of one 1 g tablet of each preparation the plasma tolbutamide
      concentration was measured by HPLC over a time-period of 48 hours. The mean AUC0
      48 values are nearly identical (998.42 vs. 997.73 micrograms x h x ml-1), while
      the Cmax values (51.1 vs. 58.8 micrograms/ml) and the tmax values (4.55 vs. 3.82
      h) show slight differences. The Westlake intervals claimed to prove
      bioequivalence lies in the 95% confidence interval between the limits 0.972 and
      1.046 (AUC), 0.896 and 0.978 (Cmax), and 0.056 and 1.346 (tmax). For example,
      this is the result of the parametric analysis considering the randomization. In
      the case of the parameters of the multiplicative model (AUC and Cmax) the
      probability of correctly concluding bioequivalence (power) between the 2
      preparations reaches 2.0. Regarding maintenance therapy it is of minor importance
      that the maximum plasma tolbutamide concentrations is 0.7 h later observed with
      the test preparation than with the standard. The results of this study allow the
      conclusion that the 2 tablet preparations are bioequivalent.

PMID- 9021454
TI  - The history and evolution of keratomileusis.

PMID- 9021456
TI  - Corneal nerve recovery after photorefractive keratectomy and laser in situ
      keratomileusis.

PMID- 9021457
TI  - Corneal coupling principles.

PMID- 9021458
TI  - Nomogram generation for keratomileusis: an introduction to multivariate analysis
      and neural nets.

PMID- 9021455
TI  - Corneal wound healing in laser in situ keratomileusis.

PMID- 9021459
TI  - Surgical technique for laser-assisted in situ keratomileusis.

PMID- 9021460
TI  - Myopic laser-assisted keratomileusis: an overview of published results.

PMID- 9021461
TI  - Midinfrared photorefractive surgery: technical standards and clinical aspects.

PMID- 9021462
TI  - "Designer surgery" in the correction of astigmatism and hyperopia.

PMID- 9021463
TI  - Intrastromal corneal ring technology.

PMID- 9021464
TI  - The current status of phakic intraocular lenses.

PMID- 9021465
TI  - Photorefractive keratectomy for correction of astigmatism after penetrating
      keratoplasty.

PMID- 9021466
TI  - Corneal modulators and their use in excimer laser phototherapeutic keratectomy.

PMID- 9021467
TI  - Excimer laser phototherapeutic keratectomy.

PMID- 9021468
TI  - Methods for calculating the requisite phototherapeutic ablation for corneal scars
      and surface irregularities.

PMID- 9021469
TI  - Tampa trephine penetrating keratoplasty: a tissue-tab technique for corneal
      transplantation. The Tampa Trephine Study Group.

PMID- 9021495
TI  - Immediate surgery versus waiting list policy in revision total hip arthroplasty.
      An economic evaluation.
AB  - An economic evaluation was carried out using a decision tree that models the
      costs and consequences of surgery at the point of consultation versus a waiting
      list policy for candidates in need of revision hip arthroplasty. The theoretical
      scenarios looked at a 2-year period wherein the immediate surgery patients
      incurred costs for 2 years after surgery, whereas the waiting list patients
      incurred costs for 1 year before and 1 year after surgery. Outcome probabilities
      were defined and applied to each treatment group, as derived from the literature
      and expert opinion. Expenditures were derived from the literature, based on
      conservative estimates of predicted pre- and postsurgical behavior for each
      scenario. This analysis indicates the potential for both substantial savings in
      resources and improved patient outcome for immediate surgery over waiting lists.
      These savings would begin at the inception of the immediate surgery protocol.
      Sensitivity analysis indicates that the conclusion is valid over a wide range of
      expenditures and probabilities.

PMID- 9021496
TI  - Early failure of the porous coated anatomic cemented unicompartmental knee
      arthroplasty. Aids to diagnosis and revision.
AB  - Unicompartmental knee arthroplasty (UKA) is performed less frequently than total
      (tricompartmental) knee arthroplasty (TKA). This study examined the range of
      presenting symptoms and usefulness of diagnostic tests to determine the failure
      mode; the outcome of surgical revision of failed UKA is also reported. From a
      consecutive prospective series of 43 Porous Coated Anatomic (Howmedica,
      Rutherford, NJ) UKAs performed between 1985 and 1992 and followed for an average
      of 64 months, 12 cases have come to revision surgery (28%). The average time to
      failure was 37 months. Symptoms preceded revision surgery by an average of 10
      months. The most common presenting symptom was pain (100%), followed by swelling
      (92%), reduced range of motion (42%), instability (42%), and clicking (17%).
      Failure was caused by polyethylene wear in 50%, loosening of the femoral
      component in 42%, and progression of patellofemoral arthritis in one patient. The
      combination of single leg standing anteroposterior radiographs and supine lateral
      radiographs detected most causes of UKA failure. A bone scan was confirmatory in
      every case of suspected loosening of the femoral component. Arthroscopy diagnosed
      polyethylene wear in two cases and progression of joint arthritis in one case and
      was not helpful in one case. Revision surgery was done with primary TKA
      components, and follow-up periods averaged 27 months. Bone stock deficiency was
      found in 58%, but required bone-grafting in only one case. Revision surgery
      successfully restored pain-free function and range of motion in all cases. Two
      year postrevision Hospital for Special Surgery scores are equal to those for
      primary TKA. Survivorship analysis showed a 33% failure rate at 57 months after
      Porous Coated Anatomic UKA when revision was the endpoint and a 41% failure rate
      when unsatisfactory clinical status was the endpoint. Regular follow-up
      evaluation is suggested for the Porous Coated Anatomic UKA.

PMID- 9021497
TI  - Impaired quality of life 10 to 20 years after primary hip arthroplasty.
AB  - The functional results in terms of quality of life 10 to 20 years after cemented
      total hip arthroplasty due to primary arthrosis were evaluated in 187 patients
      with nonrevised hips by use of the Nottingham Health Profile questionnaire.
      Function was impaired compared with age- and sex-matched random control subjects.

PMID- 9021498
TI  - Fixation of ultrahigh-molecular-weight polyethylene liners to metal-backed
      acetabular cups.
AB  - Locking mechanisms and metal-liner interface surfaces of six modular acetabular
      systems were evaluated to determine their effect on micromotion and backside wear
      of the polyethylene liner. Rotational and axial motion between the metal shell
      and polyethylene liner was measured in the Duraloc (DePuy, Warsaw, IN), Harris
      Galante (Zimmer, Warsaw, IN), Impact (Biomet, Warsaw, IN), Lip Loc (Biomet),
      Precision Osteoloc (Howmedica, Rutherford, NJ), and Reflection (Smith & Nephew
      Orthopaedics, Memphis, TN) designs at the start of each test, and at 1 million, 5
      million, and 10 million cycles. At 10 million cycles, the Lip Loc and Reflection
      cups had significantly lower rim micromotion than the Duraloc and Harris-Galante
      cups (F < .0010). The Impact, Precision Osteoloc, and Reflection cups had
      significantly lower rim subsidence than the Harris-Galante cup (F < .0025). The
      Harris-Galante cup had significantly greater rotational micromotion than the Lip
      Loc cup (F < .0074), and had significantly greater interface slippage than the
      Impact and Reflection cups (F < .0070). The Lip Loc produced significantly lower
      dome micromotion than the Harris-Galante (F < .0300). The Lip Loc and Reflection
      cups had significantly less backside wear than the Duraloc and Harris-Galante
      cups (P < .0001), the Impact cup (P < .0243), and the Precision Osteoloc (P <
      .0027) cup.

PMID- 9021499
TI  - Large amounts of polyethylene debris in the interface tissue surrounding bipolar
      endoprostheses. Comparison to total hip prostheses.
AB  - A histologic and biochemical comparison of interface membranes around femoral
      components of bipolar endoprostheses (n = 17) and total hip prostheses (n = 17)
      inserted without cement was conducted. The patients' profiles were similar in
      both groups with respect to age, sex, primary diagnosis, weight, and the interval
      between primary and revision arthroplasty. Macroscopically, marked
      circumferential abrasion of the polyethylene insert in the retrieved bipolar cups
      was noted. Histologic analysis revealed significantly larger amounts of
      polyethylene debris in the bipolar group. The membranes from the bipolar group
      also produced significantly greater amounts of prostaglandin E2 (P < .05). The
      inflammatory membranes associated with large amounts of polyethylene debris may
      have contributed to aseptic loosening and osteolysis in patients with a bipolar
      hip prosthesis.

PMID- 9021500
TI  - Factors affecting cement strains near the tip of a cemented femoral component.
AB  - A generic three-dimensional finite-element model of the upper half of the femur
      containing a cemented femoral stem of a total hip arthroplasty was developed to
      study those factors influencing cement strains near the tip of a cemented femoral
      component. This generic model was verified through another three-dimensional
      finite-element model that had been created based on the precise geometry of a
      cadaver femur implanted with a contemporary cemented femoral component. This
      cadaveric femoral reconstruction had been created with strain gauges embedded in
      the cement mantle and was then loaded under conditions simulating single leg
      stance and stairclimbing. By use of the cement strains measured experimentally in
      the cadaver femur, and comparison of them with those obtained from the finite
      element model of that cadaver femur, it was possible to establish proper material
      properties, boundary conditions, and loading conditions for the generic model.
      The generic model was then modified parametrically to determine those factors
      that influence the strains occurring within the cement mantle near the tip of a
      cemented femoral component. These models suggest that the single factor that most
      adversely influenced peak strains at or near the tip of the prosthesis was a thin
      cement mantle. This effect was present both when the cement mantle was reduced in
      thickness and when a similar effect occurred by virtue of a varus or valgus
      placement of the stem. Factors that decreased the peak cement strains near the
      tip of the femoral stem included a more flexible stem and thicker cement mantles.
      This effect of a more flexible stem could be obtained by changing the modulus of
      the metal implant by uniformly reducing the thickness of the stem, or by tapering
      the stem within the same bone geometry. Thicker cement mantles reduced both the
      axial and the shear strains occurring at the tip of the prosthesis. The presence
      or absence of a hole in the tip of the prosthesis per se, as for a centralizer,
      had no significant effect on the peak cement strains seen around the tip of the
      prosthesis; however, truncating the tip of the prosthesis from a hemisphere to a
      flat profile, which resulted in a sharp corner at the tip of the prosthesis,
      produced a 35% increase in cement strains at the tip as a result of a stress
      concentration effect. Thus, the common way of modifying the tip to have a hole
      for a centralizer, which involved truncating the tip, increased the cement
      strains occurring near the tip of the prosthesis.

PMID- 9021501
TI  - 5- to 18-year follow-up study of cemented total knee arthroplasty for patients 55
      years old or younger.
AB  - Seventy-two cemented total knee arthroplasties were performed on 52 patients who
      were 55 years old or younger. Results on 68 knees in 50 patients with an average
      follow-up period of 9.92 years are reported. The average age of the patients was
      50.7 years (range, 30-55) at the time of surgery. The diagnosis was
      osteoarthritis in 37 knees, rheumatoid arthritis in 29 knees, and ankylosing
      spondylitis in 2 knees. The average preoperative Knee Society knee score was 23
      and the average follow-up knee score was 97. All knees were rated as good or
      excellent for knee score. The average latest function score was 75 (preoperative,
      36). Both knees in one patient required revision for loose components. This
      review demonstrates that cemented total knee arthroplasty in younger patients
      with osteoarthritis and rheumatoid arthritis can attain results comparable to the
      excellent results obtained in the older age groups.

PMID- 9021503
TI  - Collection of surgical specimens in total joint arthroplasty. Is routine
      pathology cost effective?
AB  - A retrospective review of 715 consecutive cases of total joint arthroplasty (283
      hips, 432 knees), performed for a variety of indications during 1992 and 1993,
      was undertaken to assess the cost effectiveness of routine pathologic
      examination. The charts were reviewed for preoperative, operative, and pathologic
      diagnosis, and any discrepancies in diagnosis were noted. Particular attention
      was paid to pathologic findings suggestive of neoplasia or rheumatoid arthritis
      that were not noted in the preoperative or operative diagnoses. Six of the 715
      cases fit into this category, but all failed to have any clinical significance.
      No alteration in patient care resulted from routine pathologic examination. This
      paper questions the necessity of routinely submitting pathologic specimens in
      uncomplicated total hip and knee arthroplasty.

PMID- 9021502
TI  - Cementless AGC revision of unicompartmental knee arthroplasty.
AB  - Twenty-eight patients (29 knees) who had revision of a failed unicompartmental
      knee arthroplasty to total knee arthroplasty were evaluated. All revisions were
      made with cementless technique using the AGC prosthesis (Biomet, Warsaw, IN).
      Major osseous defects were found in 20 knees, and bone-grafting was used to fill
      the defects. Aseptic loosening and progression of osteoarthrosis were the main
      reasons for revision. The median follow-up period was 38 months. Twenty knees
      were excellent or good, four fair, and five poor. One tibial component had been
      revised because of loosening. Three knees with instability had been reoperated
      with a thicker polyethylene component, but one of these patients still suffered
      from instability, and revision with a constrained prosthesis was planned. One was
      revised after a deep infection. Two tibial components were suspected to be loose
      because radiographs exposed fluoroscopically revealed a complete radiolucent line
      under the component. The results with cementless revision and bone-grafting are
      comparable to the results achieved after cemented revision, and cementless
      revision is recommended in young patients and in patients with major bone loss.

PMID- 9021505
TI  - Posterior cruciate recession in total knee arthroplasty.
AB  - Incremental recession of the posterior cruciate ligament (PCL), as a part of
      ligamentous balancing in total knee arthroplasty, is critical if the PCL is too
      tight. This study was undertaken to evaluate any possible untoward effects of PCL
      recession. Twenty-one patients who underwent simultaneous bilateral total knee
      arthroplasty between 1988 and 1992 with a PCL recession performed only on one
      side (necessary to balance the knee) served as the study group. The average
      follow-up period was 4 years. The patients were evaluated subjectively, by manual
      physical testing, by radiography, and by KT-1000 arthrometry (Medmetric, San
      Diego, CA). There were no significant differences between the recessed and
      nonrecessed knees. The conclusion is that PCL recession is appropriate and safe
      long-term for the patient in whom the PCL is found to be too tight at the time of
      knee arthroplasty.

PMID- 9021504
TI  - Synovial tissue examination by frozen section as an indicator of infection in hip
      and knee arthroplasty in community hospitals.
AB  - Twenty-five surgical synovial sections were examined in 18 consecutive patients
      undergoing revision hip or knee arthroplasty (9 hips and 9 knees). All cases were
      performed in either of two community hospitals, with frozen-section tissue
      examined by multiple general pathologists. By protocol, acute inflammation was
      defined as more than five neutrophils per 60x high-power fields on multiple
      areas. A positive culture was defined as-organism growth from any surgical
      specimen. In each case, three surgical cultures and three frozen-section
      specimens were harvested from the synovium at corresponding periprosthetic
      surgical sites before antibiotics were administered. The average age of the
      patients was 68 years (range 40-87 years). There were 11 positive surgical
      cultures, 9 with positive frozen sections of synovium for acute inflammation
      (sensitivity, 82%; 95% confidence interval, 78-100%). There were 14 negative
      cultures; 13 had negative surgical frozen sections (specificity, 93%; 95%
      confidence interval, 83-100%). The positive predictive value of the test was 82%.
      There was accurate correlation between frozen section and culture in 22 of 25
      cases (88%). In this community hospital setting, frozen section examination of
      surgical synovial tissue proved to be a reasonably sensitive and specific
      predictor of deep infection in revision hip and knee arthroplasty.

PMID- 9021506
TI  - Influence of lateral release on patellar tracking and patellofemoral contact
      characteristics after total knee arthroplasty.
AB  - The influence of lateral release of retinaculum on patellofemoral kinematics and
      contact characteristics after total knee arthroplasty was investigated in vitro.
      Lateral release altered the patellar tracking in patellar flexion, rotation,
      tilting, and translation. The contact force was decreased at high flexion angles.
      The contact area was slightly decreased and the contact region shifted laterally
      on the patellar button and medially on the femoral component at most of the
      flexion angles. The results suggest that the lateral release in total knee
      arthroplasty can change some patellar tracking and patellofemoral joint contact
      characteristics.

PMID- 9021507
TI  - Effect of total hip arthroplasty on cardiovascular fitness.
AB  - Thirty patients who underwent total hip arthroplasty and 18 patients with
      medically treated arthritis participated in this study. Both groups of patients
      underwent a cardiovascular fitness exercise test on entering the study and 6
      months, 1 year, and 2 years later. Fitness was assessed by patient performance on
      a graded maximal exercise test using a bicycle ergometer and metabolic cart. In
      the group of total hip arthroplasty patients, significant improvements in
      exercise duration (P = .011), maximum workload (P = .0013), peak oxygen
      consumption (P = .0036), and percentage of predicted maximum oxygen uptake
      achieved (P = .0002) were observed during the follow-up evaluation. In the group
      of control patients, decreases in exercise duration (P = .0001), maximum workload
      (P = .0001), and workload at anaerobic threshold (P = .0108) occurred without a
      significant change in the other measures of cardiovascular fitness. The results
      indicate that resumption of routine physical activities after total hip
      arthroplasty is associated with a corresponding improvement in cardiovascular
      fitness.

PMID- 9021508
TI  - Primary total knee arthroplasty using the Genesis Total Knee Arthroplasty System:
      3- to 6-year follow-up study of 105 knees.
AB  - This prospective study analyzed data from 105 primary total knee arthroplasties
      performed in 90 patients using the Genesis Total Knee Arthroplasty System. The 34
      men and 56 women with a mean age of 68.7 years (range, 41-86 years) were
      evaluated at a mean follow-up period of 4.25 years (range, 3-6 years). Fifty-five
      procedures (52%) used cemented femoral and tibial components, 49 (47%) used
      cementless femoral and cemented tibial components, and 1 (1%) used cementless
      femoral and tibial components. The preoperative mean pain and function scores
      were 50 (range, 12-79) and 41 (range, 5-80), respectively. At the most recent
      follow-up evaluation, the mean pain score increased to 97 (range, 67-100), and
      the mean function score increased to 88 (range, 40-100). Mean preoperative range
      of motion was 104 degrees (range, 50 degrees-130 degrees) and increased to 116
      degrees (range, 80 degrees-130 degrees) at most recent follow-up evaluation.
      Clinically, there were 100 excellent results (95%). 4 good results (4%), and 1
      poor result (1%).

PMID- 9021509
TI  - Femoral cortical remodeling after uncemented total hip arthroplasty. A
      prospective radiologic study of 26 hips followed for 2 to 4 years.
AB  - Twenty-six consecutive, hydroxyapatite-coated Bi-Metric femoral stem prostheses
      (Biomet, Warsaw, IN) were studied in 20 patients. The follow-up period averaged
      37 months (range, 24-48 months). Clinical rating (Harris score) was determined
      and radiography were taken at regular intervals. Digital imaging and computer
      assisted videodensitometry were used to quantify the cortical remodeling. The
      anteroposterior radiographs of the femur were scanned and digitized, and the
      pictures were analyzed by a digital image processing software program. The
      periosteal diameter, the cortices of the femur, and the total endosteal diameter
      in five regions were determined. The mean preoperative Harris score was 50 and
      improved to 97 at the latest follow-up evaluation. After surgery, there was
      hypertrophy of the periprosthetic cortical bone and an increase in the periosteal
      diameter. The medullary canal of the operated femur did not change.

PMID- 9021510
TI  - Enhanced stability of uncemented canine femoral components by bone ingrowth into
      the porous coatings.
AB  - The following questions were answered in this study: (1) What is the initial
      stability of proximally porous-coated canine femoral components? (2) Does bone
      ingrowth occur under these conditions? (3) Is the stability enhanced by tissue
      ingrowth in vivo? The stability of proximally porous-coated femoral components of
      canine total hip arthroplasties after 6 months to 2 years of in vivo service in
      dogs was measured in vitro using displacement transducers under loads simulating
      canine midstance. This was compared with the stability of identical components
      under the same loading conditions immediately after implantation in vitro in the
      contralateral femurs. The femurs were then sectioned and bone ingrowth into the
      porous coatings was quantified. The results showed that immediately after
      implantation the implants can move as much as 50 microns, but that the bone
      ingrowth into porous coatings of canine femoral components can occur even under
      such conditions. These data also suggested that the relative motion existing at
      the time of insertion can be reduced to very small amounts (< 10 microns) by bone
      ingrowth.

PMID- 9021511
TI  - Pseudomeniscus following total knee arthroplasty as a cause of persistent knee
      pain.
AB  - Persistent pain following total knee arthroplasty is an uncommon complication
      that may have any of several causes. In the case reported here, a patient who had
      undergone total knee arthroplasty developed a symptomatic pseudomeniscus that was
      successfully treated by arthroscopic debridement. Histopathologic analysis of the
      pseudomeniscus revealed a unique fibrocartilaginous structure, which may give
      insight into its pathogenesis. Symptomatic pseudomeniscus is one of several
      postoperative complications of total knee arthroplasty for which arthroscopy may
      be indicated.

PMID- 9021518
TI  - In situ hybridization: methods and applications.
AB  - In situ hybridization (ISH) combines molecular biological techniques with
      histological and cytological analysis of gene expression. RNA and DNA can be
      readily localized in specific cells with this method. ISH has been useful as a
      research tool, and recent studies have used this technique in the diagnostic
      pathology laboratory and in microbiology for the tissue localization in
      infectious agents. Other recent developments in the applications of ISH involve
      in situ polymerase chain reaction (PCR) and in situ reverse transcription (RT)
      PCR, which can be used to detect very low levels of nucleic acids in tissues by
      taking advantage of the powerful amplification capacity of PCR. In situ PCR will
      contribute significantly to progress in this field because of the marked increase
      in the sensitivity of this method.

PMID- 9021519
TI  - Molecular genetic analysis in the pathologic evaluation of solid tumors: theory
      and practice.

PMID- 9021520
TI  - New molecular diagnostic tests for two congenital forms of anemia.
AB  - Congenital hypoplastic anemias are a rare and heterogeneous group of disorders.
      This paper reviews new molecular diagnostic tests in two distinct forms of
      congenital anemias, anemia due to transplacental infection with B19 parvovirus
      and Fanconi anemia. In both instances, molecular assays making use of
      amplification of DNA by the polymerase chain reaction have been used to diagnose
      either a specific viral infection or gene mutation responsible for a disorder.
      Recognition of these entities has important prognostic and therapeutic
      implications.

PMID- 9021522
TI  - The micro-robotic laboratory: optical trapping and scissing for the biologist.
AB  - With the addition of tightly focused laser beams, microscopes have been turned
      into elaborate preparative tools that permit not only allow detailed observation
      of a specimen but also the capture, displacement, and microdissection of
      biological samples in vitro with astonishing ease and accuracy. Laser-Tweezers
      are used to capture and manipulate cells and organelles. LaserScissors are used
      to perform microdissections at the submicrometer level. After a short technical
      description of the instrumentation and its principles of operation, several
      examples of applications are given relevant to the field of clinical research
      that could only be achieved using such modern technology. For instance,
      LaserTweezers and LaserScissors offer a unprecedented means to study the immune
      response to cancer, to control the growth of nerve cells, or expand the
      significance of assisted reproductive technologies. It is suggested that newly
      developing procedures and assays using laser-assisted technologies will prove
      beneficial for future clinical laboratory testing.

PMID- 9021521
TI  - Molecular genetic testing for adult-onset disorders: the evolving laboratory,
      physician, patient interface.
AB  - Molecular genetics is providing the power to predict and diagnose a variety of
      diseases. This is an evolving field, with new information being gained at a very
      rapid rate. Ultimately the molecular tools should be available to prevent and/or
      cure a number of diseases with genetic etiology. The molecular genetics
      laboratory is playing a pivotal role in effecting the utilization of this
      technology. However, molecular genetic testing is in many ways unlike other
      clinical laboratory testing. The process of molecular genetic testing and
      counseling is complex. The laboratory offering molecular genetic testing must be
      able to assess pedigrees, decide the proper test to perform and provide
      interpretation of the tests results obtained. Although standards governing the
      use of high-complexity genetic tests are evolving it is clear that the laboratory
      offering these tests will have to have on staff personnel trained specifically in
      molecular genetics. The challenge will be to stay abreast of evolving technology
      as well as standards and recommendations governing the use of these tests. We
      will review the process of molecular genetic testing and the issues that must be
      considered by laboratories who offer these tests.

PMID- 9021523
TI  - Serum protein standardization project in Japan: evaluation of an IFCC reference
      material (RPPHS/CRM470) and establishment of reference intervals.
AB  - Reference preparation for proteins in human serum (RPPHS), also called Certified
      Reference Material 470 (CRM 470), was prepared by the international Federation of
      Clinical Chemistry (IFCC) and is intended to serve as a new international plasma
      protein reference material. It is now being introduced into Japan. RPPHS
      possesses many excellent properties, including safety, stability, and accuracy in
      value assignment. Moreover, the physicochemical properties of its proteins are
      identical to those of fresh serum, giving it immunochemical behavior that is
      commutable with that of existing reference materials and calibrators in given
      immunoassays. Reference intervals of 13 serum proteins were determined for the
      first time using nephelometry and a new working calibrator assigned from RPPHS,
      which seems certain to play a critical role in the global standardization of
      specific protein immunoassays.

PMID- 9021524
TI  - ELISPOT assay for Chlamydia-specific, antibody-producing cells correlated with
      conventional complement fixation and microimmunofluorescence.
AB  - Chlamydia antigens cross-reactive with pneumoniae (TWAR), psittaci, and
      trachomatis strains were used to evaluate the ELISPOT assay for detecting antigen
      specific, antibody-secreting cells (ASC). Human blood specimens from healthy and
      hospitalized persons were randomly collected and tested by coating the
      nitrocellulose membrane at the base of microtiter wells. Ficoll-separated
      mononuclear cells from blood specimens collected in EDTA were incubated in the
      wells with Iscove's growth medium in CO2 atmosphere at 37 degrees C. An IgG
      specific conjugate labeled with biotin was used in an avidin-peroxidase chromogen
      system for indicating the areas (spots) of immunologically committed lymphocytes.
      Positive specimens had median levels of ASC above 8 per 10(6) cells (range 15-23
      ASC/10(6) cells). Evidence that the ELISPOT is reliable, sensitive, and specific
      includes the following:(1) immunized animal and clinical human specimens in
      control experiments were selectively reactive in the presence of antigen, but
      negative without antigen, (2) serologically characterized reference sera
      demonstrated homologous rather than heterologous reactions with the antigens, (3)
      conventional complement fixation and microimmunofluorescence on serum fractions
      of clinical specimens correlated well (P < 0.02) with ELISPOT results that were
      both TWAR- and psittaci-positive, and (4) the array of specimens (from healthy
      donors, community hospitalized, and pulmonary service patients) selected for
      their increasing likelihood in that order for being positive due to illness was
      then confirmed and supported by their respectively increasing positivity rates
      (6, 15, and 25%) for TWAR/psittaci combined. The incidence of positive specimens
      for either TWAR or psittaci was greatest (23/54, 43%) in specimens from the
      hospitalized patients and least (8/33, 24%) in specimens from healthy
      individuals. These findings suggest that ELISPOT detects chalmydial antibody
      production at the cellular level. ELISPOT positivity thus indicates previous
      exposure and would favor earlier detection.

PMID- 9021525
TI  - Effects of treatment with angiotensin-converting enzyme inhibitor (ACEI) or
      angiotensin II receptor antagonist (AIIRA) on renal function and glomerular
      injury in subtotal nephrectomized rats.
AB  - The aim of this study was to determine if treatment with angiotensin-converting
      enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (AIIRA) might
      decrease urinary albumin excretion and prevent glomerular enlargement and
      glomerulosclerosis in subtotal (5/6) nephrectomized rats. Morphometric image
      analysis of glomeruli was also performed in the subtotal nephrectomized rats. The
      nephrectomized rats were treated with ACEI (enalapril 100 mg/l), AIIRA (L-158,809
      10 mg/l) or TRX (reserpine 5 mg/ l, hydralazine 80 mg/l, and hydrochlorothiazide
      25 mg/l) and euthanized at 16 weeks after renal ablation. Treatments were started
      at 2 weeks (early treatment: Group I) or 8 weeks (later treatment: Group II)
      after the ablation. ACEI and AIIRA treatments were equally and significantly
      effective in limiting albuminuria and progression of glomerular sclerosis. TRX
      was also as effective in decreasing urinary albumin excretion and preserving the
      renal function as ACEI or AIIRA in Group I. The improvement of albuminuria,
      glomerular enlargement and sclerosis after these treatments in Group II was
      significantly less than that in Group I. It appears that the early treatment with
      angiotensin converting enzyme inhibitor, angiotensin II receptor antagonist or
      reserpine, hydralazine and hydrochlorothiazide (TRX) may prevent glomerular
      injury in human patients with renal hypertension.

PMID- 9021526
TI  - Evaluation of two novel immunoassays designed to detect HIV antibodies in oral
      fluids.
AB  - The testing of oral fluid samples for the detection of HIV antibodies offers
      several advantages over the testing of blood. Our objective was to evaluate a new
      generation of rapid and simple assays designed specifically to detect HIV-1 and
      HIV-2 antibodies in oral fluids (saliva). Serum and oral fluid pairs were
      collected from 615 high- and low-risk individuals in the United States, Peru, and
      the ivory Coast. Two different oral fluid collection devices and rapid assay
      systems included: (1) the Orapette/SalivaCard HIV-1/ HIV-2 and (2) the Omni
      Sal/ImmunoCcmb II HIV-1 and HIV-2. The corresponding serum pairs were analyzed by
      conventional ELISAs, and all reactive sera were confirmed with HIV-1 and HIV-2
      Western blots. The results indicated a 100% sensitivity for both rapid oral fluid
      assays, including successful detection of HIV-2 antibodies. Specificities ranged
      from 99.8% to 100%. One sample produced a reactive result by the SalivaCard while
      being nonreactive by the other assays including the Western blots. Both assays
      performed excellently, indicating that antibodies to HIV can be detected reliably
      in oral fluids by simple and rapid assays. This combination of rapid testing
      technology and the use of easily collected oral fluid samples offers an efficient
      and accurate alternative to conventional testing and can be appropriately applied
      to a variety of testing situations for the laboratory diagnosis of HIV infection.

PMID- 9021527
TI  - Quantitation of soluble E-receptor of T lymphocytes in serum from HIV-1 positive
      patients.
AB  - Human T lymphocytes carry a membrane receptor for sheep erythrocytes (E) related
      to the CD2 molecule. The E-receptor is found in a soluble from (Rs) in serum and
      can be quantitated by "rocket electrophoresis" using an anti-Rs serum obtained by
      immunizing sheep with autologous erythrocytes coated with Rs. Increased serum
      levels of Rs are found in patients with diseases associated with
      immunodepression. In the present study, 14 asymptomatic HIV-1 seropositive
      individuals were investigated regarding their Rs levels and delayed
      hypersensitivity skin tests every 3 months for a period of 35 months. All these
      patients progressed to AIDS in this period. Rs serum levels have also been
      quantitated in 14 normal individuals. The mean Rs values in normal individuals,
      asymptomatic, and AIDS patients were, respectively: 4.8 +/- 1.5 mm (SD), 9.6 +/-
      1.9 mm (SD) and 11.3 +/- 2.4 mm (SD). An increase of Rs serum levels was observed
      when we compared normal individuals with CDC-II and CDC-IV clinical stage
      patients (P < 0.05, Mann-Whitney test) and CDC-II and CDC-IV patients, (P < 0.05,
      Wilcoxon test). We have observed a depressed delayed hypersensitivity response to
      ubiquitous antigens in CDC-IV patients. Our results indicate that Rs serum levels
      can be used as a progression marker in HIV infected patients.

PMID- 9021536
TI  - The Scottish tonsillectomy audit. The Audit Sub-Committee of the Scottish
      Otolaryngological Society.
AB  - Regional specialist societies offer a valuable mechanism for the conduct of
      medical audit. The experience of the audit sub-committee of The Scottish
      Otolaryngological Society in conducting an audit on laryngeal cancer encouraged
      us to undertake a larger audit of tonsillectomy practice in Scotland. Although
      the number of tonsillectomies performed has declined over the last 10 years, they
      still account for about 20 per cent of all operations performed by
      otolaryngologists and as such are a major consumer of resources (Personal
      communication-Directorate of Information Services, Information and Statistics
      Division. NHS in Scotland, Management Executive, Edinburgh). The Scottish
      tonsillectomy audit was devised to define current practice, review indications
      for surgery and recommend such modifications in practice as may be necessary to
      optimise patient care and the use of resources. Funding was obtained from the
      Clinical Resource and Audit Group (CRAG) of the Scottish Home and Health
      Department. Data on current practice was collected during the period February
      1992 to January 1993. Proformas were completed by medical, administrative and
      secretarial staff in all participating hospitals, collected by an audit secretary
      and passed to the relevant data collection centre. Data was then entered into a
      specially designed database before being forwarded to the audit co-ordinator
      based in Dundee for collation. Six and 12 months following surgery, all
      inpatients were sent a questionnaire to obtain data on the efficacy of the
      operation. Data were obtained from a total of 9,773 patients. Two thousand and
      seventy-nine of these were seen as both outpatients and inpatients, 4,309 were
      outpatients only and 3,385 were inpatients only. Four thousand, one hundred and
      one patients returned at least one follow-up questionnaire. The topics audited
      included source and reason for referral, indications for surgery, grade of staff
      involved, type of surgery and length of stay in hospital. In agreement with
      previous studies (H.M.S.O., 1989), differences were found in the rates of
      tonsillectomy performed in different Health Boards. Although the highest referral
      and operation rates were found in the Highland region, referral and operation
      rates did not correlate in all other areas. Recurrent tonsillitis was the most
      frequent principal reason for the decision to operate although there were
      differences between Health Boards for other indications including obstructive
      symptoms. Most patients had symptoms for two to three years although some
      patients had been affected for 40 years prior to being listed for tonsillectomy.
      Some are ENT services were consultant-based while others involved more junior
      staff. The grade of staff involved did not appear to affect the decision made at
      the Outpatient Department (OPD) or the outcome of the operation. Ninety-eight per
      cent of patients who returned the questionnaire were glad that the operation had
      been performed. Recommendations regarding changes in tonsillectomy practice are
      given.

PMID- 9021537
TI  - Frequency of hepatitis B virus e-minus mutants varies among patients from
      different areas of China.
AB  - Four hundred forty-six serum samples from HBsAg-positive chronic hepatitis B
      patients were collected from five areas in China (eastern coastal city, Shanghai;
      southwestern inland city, Chengdu; mid-inland city, Wuhan; southern island city,
      Haikou; and northeastern city, Changchun). Precore stop codon variants (e-minus
      mutants) were screened using a rapid method of polymerase chain reaction (PCR)
      amplification of a precore and partial core gene fragment (nucleotides 1785
      2172), followed by dot-blot hybridization with specific oligonucleotide probes
      (M0, and M1 + M2). The sequence of the M0 probe covered the distal precore region
      of wild-type virus (nucleotides 1887-1908), and the sequences of the M1 and M2
      probes were from sequences mutated at nt. 1898, (TGG-->TAG) with or without
      additional change at nt. 1901. A significantly lower incidence of the precore
      stop codon was found in anti-HBe-positive serum samples from Haikou (17.6%),
      whereas in other areas the percentages of this mutation in anti-HBe positive sera
      ranged from 47.4% to 78.9%. In HBeAg-positive samples, the rate of e-minus mutant
      in coexistence with wild-type virus was low in specimens from Haikou (9.5%) and
      Changchun (2.9%) compared to other areas in China. In contrast, coexistence of
      mutant and wild-type virus was frequently detected in samples from Wuhan (50.0%).

PMID- 9021538
TI  - In situ immune responses in Crohn's disease: a comparison with acute and
      persistent measles virus infection.
AB  - The implied aetiological association of measles virus with Crohn's disease would
      be supported by detection of an immune response to infected cells in affected
      tissues. This study sought to detect and characterise in situ immune responses to
      measles virus in both acutely and persistently infected tissues, and in
      particular, Crohn's granulomata. Tissue sections from patients with Crohn's
      disease (n = 17), tuberculosis (n = 9), acute intestinal ischaemia (n = 5), acute
      measles pneumonitis (n = 2), acute measles appendicitis (n = 1), subacute
      sclerosing panencephalitis (SSPE; n = 1), and measles inclusion body encephalitis
      (MIBE; n = 1), were examined. Single and double immunohistochemical labelling was
      performed to identify both cytotoxic lymphocytes (CD8, TIA, perforin, Leu 7,
      CD45RO, CD45RA) and macrophages (KP1). The relationship of these cells to measles
      infected cells was examined by double immunolabelling with antimeasles virus
      nucleoprotein antibody. In both acute measles appendicitis and SSPE, CD8+/TIA
      cytotoxic lymphocytes (CTL) targeted infected cells. In the cases of Crohn's
      disease (13/17), MIBE, fatal pneumonitis, and one tuberculous granuloma, that
      were positive for measles virus, infected cells appeared to be targeted by
      macrophages rather than CTL. CTL in both tuberculous and Crohn's granulomata were
      similar in their peripheral distribution, number, and phenotype. The data suggest
      that measles-specific CTL responses may be attenuated in Crohn's disease compared
      with acute measles appendicitis and SSPE, and secondly, that an abnormal
      macrophage response to persistent measles virus infection of the intestine may
      result in granulomatous inflammation.

PMID- 9021539
TI  - Outbreak of gastroenteritis in military recruits associated with serotype 3
      astrovirus infection.
AB  - A serotype 3 astrovirus was identified in stool samples from an outbreak of acute
      gastroenteritis that occurred among military recruits in France. Sixteen stools
      samples and eight pairs of acute- and convalescent-phase serum were collected
      from affected individuals. Astrovirus was detected in two stool samples by
      electron microscopy and in four stool samples by reverse transcriptase-polymerase
      chain reaction (RT-PCR). Seroconversion to the astrovirus present in one stool
      was detected in seven patients by using solid-phase immune electron microscopy
      (SPIEM) and dot blot. For three patients, the serological results were consistent
      with the PCR results, indicating that astrovirus was a cause of gastroenteritis
      in these young adults. This study describes the characterization of the serotype
      3 astrovirus associated with this outbreak. The virus has a buoyant density in
      cesium chloride of 1.365 gm/ml and contains two proteins immuno-precipitated with
      rabbit serum. Only the larger protein was recognized by immunoblotting using a
      convalescent-phase human serum. The protein composition of this virus differs
      from that reported for serotype 1 astrovirus, indicating heterogeneity in the
      capsid composition among astrovirus serotypes.

PMID- 9021540
TI  - Development of a reverse transcription-polymerase chain reaction assay for
      diagnosis of lymphocytic choriomeningitis virus infection and its use in a
      prospective surveillance study.
AB  - Lymphocytic choriomeningitis virus (LCMV), which is one of several arenaviruses
      that are pathogenic for humans, causes encephalitis and meningitis in man. In
      this study, single-stage and nested reverse transcription-polymerase chain
      reaction (RT-PCR) assays were developed that targeted the GPC and N genes of
      LCMV. Both assays detected < 1 TCID50 unit of LCMV. These assays were used to
      measure the incidence of LCMV infection by testing cerebrospinal fluid (CSF)
      samples with > or = 10 leukocytes/microl collected over 1 year from patients
      undergoing lumbar puncture for diagnostic reasons at two Birmingham hospitals.
      Samples were tested for the presence of LCMV RNA by using the RT- PCR assay and
      for LCMV-specific IgM antibody by using an ELISA assay. None of the specimens
      collected from 813 patients was positive by either assay. Although no cases of
      acute infection were detected, 4% (11/272) of serum collected from a subset of
      patients was positive for LCMV-specific IgG. A significantly greater rate of
      seropositivity was found among subjects over 60 years of age (9.4%; P < 0.025)
      than was found in younger subjects (2.4% at 30-59 years of age; 0% at < 30 years
      of age). These data suggest that serious central nervous system disease due to
      LCMV infection is not common in this population. The high rate of seropositivity
      in those over 60 years of age suggest that infection was once more common.

PMID- 9021541
TI  - Prevalence of antibodies to human caliciviruses (HuCVs) in Kuwait established by
      ELISA using baculovirus-expressed capsid antigens representing two genogroups of
      HuCVs.
AB  - Baculovirus recombinant-expressed antigens of Norwalk viruses (rNV) and a Mexico
      strain (rMX) of the Snow Mountain serogroup of human caliciviruses (HuCVs) were
      used in enzyme immunoassays to study the antibody prevalence among the Kuwaiti
      population and foreign workers employed in Kuwait. The antibody titers in 16
      different age groups which ranged from neonates to centenarians were investigated
      by testing eight different dilutions of each serum (1:200-1:25,600). The results
      indicate that NV infection is widespread in Kuwait and affects all age groups
      Ninety-eight percent of the 433 serum samples tested had antibodies to rNV. In
      the 50-79-year, old age group, the antibody levels to rNV were higher and
      significantly different from those in children 0-7 years old. In infants, the rNV
      antibodies did not diminish by 4 months of age and their titer steadily increased
      with age. When 414 of these sera samples were tested for antibodies to rMX, 96%
      positive serological responses were observed. Antibody titers to rMX were reduced
      in infants from 4 to 11 months; however, 95% of the samples were positive. These
      data indicate that children born in Kuwait are infected with Norwalk-like viruses
      at a very early age. Finally, antibodies to rNV and rMX were found in 98% of 151
      and in 95% of 148 foreign workers, respectively.

PMID- 9021542
TI  - Detection of HPV DNA in trichilemmomas by polymerase chain reaction.
AB  - Paraffin sections of 11 formalin-fixed trichilemmomas were investigated for the
      presence of human papillomavirus (HPV) DNA by the polymerase chain reaction (PCR)
      with the degenerated consensus primer pairs. PCRs were conducted with different
      annealing temperatures. When the annealing temperature was reduced from 55
      degrees C to 50 degrees C, amplification products of the expected size were
      obtained for all 11 cases investigated. Determination of the HPV type was
      performed by cloning and sequencing of the amplification products. The sequence
      analysis of the eleven cloned amplicons gave the following data: based on
      sequence comparison with published amino acid sequences, the best homology was
      found to epidermodysplasia verruciformis (EV)-associated HPVs (supergroup B). In
      four specimens an HPV type 23 related type was found; five specimens contained
      HPV sequences which did not match with one of the known HPV types, but had the
      closest homology to HPV types 15, 17, and 37. Three of the HPV variants which had
      not been characterised, displayed identical sequences. Two additional HPV
      amplification fragments displayed played 100% homology to HPV-6b. These results
      demonstrate, for the first time, the presence of HPV DNA in trichilemmomas. The
      sequence data suggest that HPV variants or types in trichilemmoma are members of
      the EV-associated HPV supergroup B.

PMID- 9021543
TI  - Age distribution of antibodies to human papillomavirus in children, women with
      cervical intraepithelial neoplasia and blood donors from South Africa.
AB  - Sera from 95 women with cervical intraepithelial neoplasia (CIN), 95 age-matched
      female blood donors, and 155 children aged between 1 and 12 years were tested by
      enzyme-linked immunosorbent assay (ELISA) for levels of serum IgG to three human
      papillomavirus (HPV) peptides (HPV-16 E2 [E2-16], HPV-18 E2 (E2-18], HPV-16 L1
      [L1-16]), as well as HPV-16 virus-like particles (VLP-16) and bovine
      papillomavirus type 1 virus-like particles (BPV-VLP). In the adult group
      antibodies to E2-16 and VLP-16 were significantly associated with CIN when
      compared to the blood donor controls (P = .039 and P = .002, respectively). In
      women with CIN there was an increase in seropositivity to E2-16 and a decrease in
      seropositivity to VLP-16 with age. Antibodies to HPV-16 E2 could therefore be an
      important marker of CIN in women over 40 years of age, whereas antibodies to VLP
      16 could be a marker for CIN in younger women. There was no correlation with CIN
      and antibodies to E2-18, L1-16, and BPV-VLP. In the children's sera antibodies
      were detected to E2-16 (44.5%), E2-18 (18.7%), L1-16 (20%), VLP-16 (4.5%), and
      BPV-VLP (5.1%). Between the ages of 3 and 12 years the prevalence of antibodies
      to E2-16 decreased with age. The presence of antibodies to HPV-16 in young
      children indicated infection with either HPV-16 or a related virus. HPV DNA
      isolation from children could help resolve this question.

PMID- 9021544
TI  - Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid
      with clinical outcome in Japanese encephalitis patients.
AB  - To investigate the prognostic role of tumour necrosis factor (TNF) in Japanese
      encephalitis virus (JEV) infection, we measured the immunoreactive forms of TNF
      concentrations in the serum and cerebrospinal fluid (CSF) of 47 laboratory
      confirmed cases of JE. It was observed that TNF levels were elevated (> 15
      pgm/ml) in all the 47 serum samples (range 19.4-923.8 pg/ml), while in 46/47 CSF
      samples TNF was elevated (range 10.8-376 pg/ml). The mean (SD) TNF levels in the
      serum of fatal cases was 234.34 pg/ml (304.40) as compared to the mean of 85.31
      pg/ml (SD 153.92) in nonfatal cases. Similar observations were also made with
      respect to the TNF levels in the CSF; the mean of fatal cases was 69.39 pg/ ml
      (SD 39.00) in contrast to the mean of 62.41 pg/ml (SD 75.25) of nonfatal cases.
      The increase in TNF levels did not show any correlation to the duration of
      illness. It was further observed that the mortality rate increased with
      increasing concentrations of TNF in the serum and CSF. Correlation of laboratory
      parameters to final outcome revealed that TNF concentrations above 50 pg/ ml in
      serum correlated significantly (P = .05) with a fatal outcome, whilst high levels
      of JEV-IgM antibodies (> 500 units) in the CSF correlated with a nonfatal outcome
      (P = .03). These results suggest that TNF can be used as a possible
      prognosticator of a fatal outcome in JEV infection.

PMID- 9021545
TI  - Intravascular fibrin thrombi and endothelial cell damage in central giant cell
      granuloma.
AB  - Two cases of central giant cell granuloma were studied ultrastructurally. The
      majority of vessels showed intravascular fibrin thrombi and endothelial cell
      damage, with gaps in their walls. Plasma, red cells and fibrin were seen
      subendothelially. The basal lamina was absent from endothelial cells where these
      components were in contact with their plasma membrane; otherwise it showed
      multiplication. It is suggested that the absence of basal lamina is the result of
      degeneration and that these vessels are probably venules and capillaries rather
      than lymphatics. Myofibroblasts were the dominant stromal cells. Giant cells had
      little phagocytic activity. It seems that the main function for the stromal cells
      is the repair of the haematoma and the damaged vessels. It is proposed that the
      term giant cell reparative granuloma is appropriate, but it should not be used
      indiscriminately for all jaw lesions containing giant cells.

PMID- 9021546
TI  - Cyclosporin A upregulates prostaglandin E2 production in human gingival
      fibroblasts challenged with tumor necrosis factor alpha in vitro.
AB  - The effect of cyclosporin A (CsA) on prostaglandin E2 (PGE2) production in human
      gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-alpha) was
      studied. TNF-alpha (1-100 ng/ml) dose-dependently stimulated PGE2 formation in 24
      h cultures. CsA (1-100 ng/ml) did not induce PGE2 formation itself but
      potentiated TNF-alpha induced PGE2 formation in gingival fibroblasts in a manner
      dependent on the concentrations of both CsA and TNF-alpha. TNF-alpha (10 ng/ml)
      stimulated the release of [3H]-arachidonic acid (AA) from prelabelled fibroblasts
      that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5
      20 microM/ml) to the cells resulted in enhanced PGE2 formation that was not
      potentiated by CsA (100 ng/ml). Furthermore, CsA (100 ng/ml) did not further
      increase the level of cyclooxygenase-2 mRNA induced by TNF-alpha (10 ng/ml),
      although PGE2 formation was enhanced. The results indicate that CsA and TNF-alpha
      act in concert on PGE2 formation in gingival fibroblasts, which may be of
      importance in the pathogenesis of gingival overgrowth induced by the drug.

PMID- 9021547
TI  - Immunohistochemical localization of fibroblast growth factor-1 (FGF-1), FGF-2 and
      fibroblast growth factor receptor-1 (FGFR-1) in pleomorphic adenoma of the
      salivary glands.
AB  - Fibroblast growth factor-1 (FGF-1) and FGF-2 are heparin-binding polypeptides
      that are potent mitogens for neoplastic cells. In this study, fibroblast growth
      factor-1 (FGF-1), FGF-2, and fibroblast growth factor receptor-1 (FGFR-1) were
      immunohistochemically analyzed in 10 patients with pleomorphic adenoma of the
      salivary gland by using specific monoclonal antibodies. The tumor tissues were
      histopathologically classified as: tubular, solid, myxoid or chondroid. Both FGF
      1 and FGF-2 were immunohistochemically identified in the tumor cells of all
      histological types. In addition, immunoreactive FGF-2 was also found in the
      basement membrane of tubular type tumor cells. Conversely, FGFR-1-positive tumor
      cells were essentially confined to the tubular and solid areas of tumors. Tumor
      cells in the myxoid and chondroid areas were FGFR-1 immunonegative. These results
      suggest that the co-expression of FGF and its receptor appears to be related to
      the proliferative activity of tumor cells in the tubular and solid areas, whereas
      loss of FGF receptor expression may be associated with the differentiation of
      tumor cells into myxoid and chondroid tissue types.

PMID- 9021548
TI  - Raised levels of circulating VCAM-1 and circulating E-selectin in patients with
      recurrent oral ulceration.
AB  - Endothelial cell (EC) adhesion molecules VCAM-1 (vascular cell adhesion molecule
      1), E-selectin and ICAM-1 (intercellular adhesion molecule-1) are essential for
      the binding of inflammatory cells to ECs. Recently, circulating forms of these
      molecules have been detected in a number of vasculitic disease processes.
      Recurrent oral ulceration (ROU) has some features of a vasculitic disease
      process. The purpose of this study was, therefore, to compare cVCAM-1, cE
      selectin and cICAM-1 levels in 50 patients with ROU and 50 age- and sex-matched
      controls. Levels of circulating adhesion molecules were quantified using specific
      "sandwich" ELISA assays. The cVCAM-1 and cE-selectin levels were significantly
      raised in ROU patients (P < 0.00005 and P < 0.05, respectively) but there was no
      significant increase in cICAM-1 levels. These findings may result from
      endothelial cell activation or damage at the ulcer site.

PMID- 9021549
TI  - Myocutaneous flaps in patients with head and neck cancer retain their
      immunological capacities in an activated functional state.
AB  - Free/pedicled myocutaneous flaps used as functional replacement after radical
      dissection of advanced stage squamous cell carcinomas of the oral
      cavity/oropharynx were examined by immunohistochemistry (APAAP-technique).
      Biopsies from eight patients were taken at the time of surgery and at 3 and 5
      months post-operatively. Fifteen monoclonal antibodies were used to detect
      surface antigens as markers of phenotypic changes of immune competent cells. In
      post-operative biopsies all antigens investigated increased significantly.
      Significantly higher numbers of CD45RO+ (P < 0.01) and CD45RA+ (P < 0.001)
      leukocytes were detectable. The majority of these leukocytes were TcR alpha/beta
      +/CD3+ T-cells, which increased in the CD4 (P < 0.05) and the CD8 (P < 0.001)
      subset. In addition, B-cells (P < 0.05), granulocytes (P < 0.05), NK cells (CD16+
      lymphocytic cells; P < 0.05) and mature macrophages (25F9+cells; P < 0.01) were
      increased. Intra- and subepidermally a significantly (P < 0.01) higher number of
      dendritic-/Langerhans cells (CD1a+) was detectable. In post-operative biopsies,
      the activation-associated antigens ICAM-1, VCAM and HLA-DR were expressed on
      significantly more mononuclear-/endothelial cells and on keratinocytes. Our
      findings indicate that the myocutaneous flaps still contained cells with
      immunological capacities.

PMID- 9021550
TI  - Antibodies to epithelial components in oral lichen planus (OLP) associated with
      hepatitis C virus (HCV) infection.
AB  - Oral lichen planus (OLP) is a common chronic inflammatory disorder sometimes
      associated with hepatitis C virus (HCV) infection. An increased prevalence of
      autoimmune markers has been reported in patients with HCV infection. The aim of
      the present study was to determine, by conventional indirect immunofluorescence,
      the nature and frequency of circulating antibodies to epithelial antigens in the
      sera of HCV-positive patients who also have OLP. The study comprised four groups:
      14 patients with OLP and HCV infection. 14 HCV-seronegative patients with OLP, 21
      HCV-seropositive patients without OLP and 18 healthy controls. We found a
      significant association between the concomitance of OLP and HCV infection and the
      presence of such antibodies. It is concluded that some patients with HCV
      associated OLP may have circulating antibodies to epithelial antigens, although
      their precise aetiological role in the development of this disease in HCV
      infection remains unknown.

PMID- 9021551
TI  - Effect of nicotine on arachidonic acid metabolites and epithelial parameters in
      rat oral mucosa.
AB  - This study examined the effects of nicotine on oral mucosal levels of eicosanoids
      and on histologic parameters, including keratinocyte proliferation. Surgically
      created canals in the mandibular lips of 20 male Sprague Dawley rats received
      either nicotine or saline in a cotton pellet twice daily for six weeks.
      Thromboxane B2 (TxB2) levels were depressed (P < 0.05) in nicotine treated
      tissues compared to saline treatment (5.8 +/- 1.0 vs 13.4 +/- 2.1 pg/mg). Within
      the nicotine group, TxB2 concentrations were lower (P < 0.05) at the nicotine
      site compared to the posterior site (18.3 +/- 5.4 pg/mg). There was also a trend
      towards reduced 6-keto-PGF1 alpha in the nicotine-treated tissues compared to
      saline-exposed sites. These alterations in cyclooxygenase metabolites were not
      accompanied by changes in epithelial proliferation or histologic parameters.
      12(S)-hydroxyeicosatetranoic acid (12-HETE) and leukotriene B4 (LTB4) were not
      affected by nicotine. Therefore, nicotine may not be directly responsible for the
      hyperplasia at habitual tobacco placement sites, but may contribute to
      alterations in cyclooxygenase products of arachidonic acid metabolism.

PMID- 9021552
TI  - Salivary gland scintigraphy with 99mTc-pertechnetate in Sjogren's syndrome:
      relationship to clinicopathologic features of salivary and lacrimal glands.
AB  - Salivary gland scintigraphy was performed on 52 patients who were suspected of
      having Sjogren's syndrome (SS), and the results were compared with
      clinicopathologic features of the salivary and lacrimal glands. The time-activity
      curves which were obtained from computer-assisted analysis of 99mTc-pertechnetate
      (99mTc) scintigraphy were classified into four types (normal, median, flat and
      sloped types). The stimulated parotid flow rate decreased and the incidence of SS
      related sialographic and histopathologic findings increased significantly as the
      scintigraphic abnormality advanced. In addition, the lacrimal gland function
      decreased and the proportion of patients diagnosed as having keratoconjunctivitis
      sicca (KCS) increased significantly as the scintigraphic abnormality advanced.
      These results indicate that the results of scintigraphy are related not only to
      the clinicopathologic features of the salivary glands but also to the lacrimal
      gland function in SS.

PMID- 9021553
TI  - Amyloid deposits in labial salivary glands identified by electron microscopy.
AB  - Abnormal proteinaceous deposits identified by light microscopy as amyloid in
      labial salivary gland biopsies were studied by transmission electron microscopy
      in order to establish their ultrastructural characteristics. Results showed fine
      fibrils approximately 10 nm in diameter located in close relation to the basal
      lamina of the secretory end-pieces and ducts as well as in the interstitial
      connective tissue stroma of labial salivary glands; these are the typical
      features of amyloid. Thus, the present study confirms the light microscopy
      diagnosis of amyloid deposits in labial salivary gland biopsies, supporting the
      use of lip biopsy as a readily accessible method for the diagnosis of secondary
      amyloidosis.

PMID- 9021554
TI  - Oral cryptococcosis: case report of salivary gland involvement in an AIDS
      patient.
AB  - Salivary cryptococcosis was disclosed at autopsy in an AIDS patient with
      disseminated C. neoformans infection. H & E staining was not suitable to
      demonstrate the occurrence of C. neoformans in many tissues; Alcian blue gave the
      best results.

PMID- 9021555
TI  - Childhood intussusception: ultrasound-guided Hartmann's solution hydrostatic
      reduction or barium enema reduction?
AB  - A comparison was made of the efficacy of ultrasound guided Hartmann's solution
      hydrostatic reduction on 23 patients (US group) with the same number of
      consecutive patients in whom hydrostatic reduction was done by barium enema (BE
      group) under fluoroscopy for childhood intussusception. The US group was
      diagnosed by ultrasound scan and reduction was attempted under the guidance of
      ultrasonography with Hartmann's solution at 100 mm Hg pressure. Excluded were
      patients older than 12 years, patients in shock, patients with peritonitis, bowel
      perforation, and gross abdominal distension as well as recurrent intussusception
      of more than three episodes. There were three patients excluded in this group.
      The diagnosis of intussusception and complete reduction were confirmed by
      gastrografin enema. This US group had three recurrences (3 of 26, 11.5%), one
      lead point (1 of 23, 4.4%), and 19 successful reductions (19 of 26, 73%).
      Incidentally, there were also three patients excluded in this period of barium
      enema reduction. There was only one recurrence (1 of 24, 4.2%), one leadpoint (1
      of 23, 4.4%), and 12 successful reductions (12 of 24, 50%) in these 23 BE
      patients. The success rates for the ileo-colic intussusceptions with Hartmann's
      solution reduction and barium enema reduction were 91% (19 of 21) and 55% (12 of
      22), respectively (P = .00865). There was no complication in either group, and
      the accuracy of diagnosing a complete reduction was 100% in both forms of
      reduction. Hence, ultrasound-guided hydrostatic reduction for childhood ileocolic
      intussusception is preferred because it is safe, accurate, has a higher success
      rate, and can avoid radiation exposure risk.

PMID- 9021556
TI  - The discovery and a study of the adventitia rectalis, a fibrous layer of the
      rectal wall.
AB  - In sacral anoplasty, it is frequently found that an outer layer of the rectal
      wall, which resembles the structure of the taenia bands of the colon, limits the
      elasticity of the rectum making it different from the small intestine, hence
      preventing the rectal stump from being advanced to reach the perineum. Results of
      autopsy studies on 40 human babies and 40 dogs showed that a special collagenous
      fibrous layer called adventitia rectalis was found to limit the free expansion of
      the rectal wall. This was responsible for keeping the rectum a straight tubular
      shape with a fixed volume. This tissue plays an important role in bowel movement
      by defining a threshold of intrarectal pressure in the bowel reflex of defecation
      and by transmitting the expulsive force from the abdomen above down to the anal
      opening. This discovery may explain why (1) in Hirschsprung's disease, the
      preservation of the rectal wall in Soave's or Rehbein's procedure or partial
      preservation in Duhamel's operation will preserve better bowel function; (2) in
      atresia ani, rectal tapering results in better bowel control than rectal pouch
      amputation; and (3) in sacral anoplasty, multiple releasing incisions of
      adventitia rectalis at different levels will lengthen the rectal stump to about
      double its original length to reach the perineal incision, and the divided fibers
      will soon regenerate.

PMID- 9021557
TI  - Histopathologic study of esophageal atresia and tracheoesophageal fistula in an
      animal model.
AB  - A histopathologic study of tracheoesophageal anomalies was conducted on an
      Adriamycin-treated animal model to determine how closely it resembles the human
      pattern. Adriamycin was administered (2 mg/kg body weight) to timed-pregnant rats
      on days 6 through 9 of gestation. The fetuses were recovered at term, dissected
      and prepared for histological studies. Dissection showed a similar range of
      variants of tracheoesophageal anomalies as seen in humans. Esophageal atresia
      with distal tracheoesophageal fistula was by far the most common type. Other
      varieties were seen such as esophageal atresia without a fistula, tracheal
      atresia and hypoplastic esophagus with atrophic mucosa, and muscle coat. Serial
      sectioning of the distal segment showed tracheobronchial elements extending to a
      variable distance from the origin of the fistula.

PMID- 9021558
TI  - Does calcitonin gene-related peptide act as a chemoattractant for rat
      gubernacular cells?
AB  - Calcitonin gene-related peptide (CGRP) receptors are located in the cremaster
      muscle of the gubernaculum of rats, and causes gubernacular contraction in vitro,
      suggesting that CGRP plays an important role in testicular descent. It has been
      postulated that CGRP released from the genitofemoral nerve acts as a
      "chemoattractant" for gubernacular migration to the scrotum. The aim of this
      study is to investigate whether the gubernacular cells of rats exhibit a
      chemotactic response to CGRP in vitro. Chemotaxis of gubernacular cells from
      Sprague-Dawley rats (1 to 6 days old) was measured using blind-well chambers. The
      migration of cells, which passed from the upper to the lower compartment through
      a polycarbonate filter, were counted using microscopy. The lower compartment
      included 10(-11), 10(-10), 10(-9), and 10(-8) M CGRP or phosphate buffered saline
      (PBS) as control. The chemotactic index (CI) was defined as the ratio of
      migration toward CGRP versus PBS as control. There was no significant migration
      even at varying CGRP concentrations. Isolated rat gubernacular cells therefore
      did not exhibit a chemotactic response to CGRP and the role CGRP plays in
      testicular descent still remains unclear. This result does not exclude the
      possibility that the gubernaculum responds to CGRP as a whole organ rather than
      as individual cells.

PMID- 9021559
TI  - Prenatal phthalate causes cryptorchidism postnatally by inducing transabdominal
      ascent of the testis in fetal rats.
AB  - Phathalate esters, which are commonly used as plasticizers for polyvinyl
      chloride, are also well known to disturb Sertoli cells. This study aims to show
      the effect of prenatally administered phthalate on testicular descent in pre- and
      postnatal rats. Pregnant rats were exposed to mono-n-butyl phthalate (MBP) by
      gavage from the 15th to the 18th gestational days. Rats administered with solvent
      only were used as controls. In 20-day-old fetuses (n = 15), the degree of
      transabdominal testicular ascent in relation to the bladder neck was thus found
      to be significantly higher in MBP-treated rats than that of the controls (n =
      19). In addition, in MBP-treated male offspring (n = 26), 22 rats showed either
      bilateral or unilateral cryptorchidism at the age of 30 to 40 days old, and the
      occurrence of cryptorchidism was 84.6%. By contrast, the occurrence of
      cryptorchidism was 0% in the control rats (n = 15, P < .001). It is therefore
      suggested that prenatal exposure to MBP may disturb the Sertoli cells and elevate
      the fetal testes relative to the bladder neck while also inducing cryptorchidism
      postnatally. Sertoli cells may thus play an important role in the transabdominal
      descent of the testis by secreting Mullerian-inhibiting substance (MIS), which is
      known to act as a putative mediator of the transabdominal phase.

PMID- 9021560
TI  - External anal sphincter dysfunction and postoperative bowel habits of patients
      with Hirschsprung's disease.
AB  - An electromyogram (EMG) of the external and sphincter (EAS) was obtained both
      before and after surgery in five patients with Hirschsprung's disease and eight
      normal control patients. The EMG, evoked by the transrectal stimulation of the
      pudendal nerve, was recorded at both the sacral and anal regions to investigate
      the deep and superficial EAS, respectively. In eight control patients, the EMG at
      the sacral region consisted of a polyphasic wave with apparently two or three
      major peaks, and the simple monophasic wave with one or two peaks was found at
      the anal region. Its peak corresponded to the early peaks in the sacral region.
      The mean onset latency of the EMG in the sacral region was 2.8 ms. Four patients
      with Hirschsprung's disease also exhibited responses that were similar to the
      controls, and their postoperative bowel habits were satisfactory. However, the
      remaining one patient, who still required a daily enema after surgery, exhibited
      an apparently different response, which was monophasic at both the sacral and
      anal regions with a long onset latency of 5.0 ms before and after surgery. It is
      postulated that some cases with Hirschsprung's disease might be associated with
      an EAS dysfunction before surgery, which possibly led to the development of
      postoperative bowel dysmotility.

PMID- 9021561
TI  - More than 10 years' follow-up to total colonic aganglionosis--severe iron
      deficiency anemia and growth retardation.
AB  - Seven cases of total colonic aganglionosis were reviewed with a follow-up period
      of 10 to 26 years, focusing on the relationship between the length of aganglionic
      ileum and postoperative metabolic disorders. Pulled-through ileum ranged from 0
      to 65 cm from the ileocecal valve, and suprapelvic side-to-side anastomosis was
      performed between the pulled-through ileum and 17 to 40 cm of aganglionic colon
      (left side and transverse colon, four; right side colon, one; no colonic patch,
      two). Hemoglobin level in three out of four patients with ileal involvement of
      more than 25 cm was below 11 g/dL (10.9, 7.7, 6.6 g/dL, respectively). Serum iron
      level was less than 30 micrograms/dL (27, 21, 20, 18 micrograms/dL, respectively)
      in four out of five patients with ileal involvement of more than 10 cm. Serum
      vitamin B12 level was below 100 (100, 46 pg/dL, respectively) in two patients
      whose pulled-through ileum was 45 cm and 65 cm, respectively from the ileocecal
      valve. One patient needs periodical parenteral iron therapy and one was treated
      as megaloblastic anemia. In the patients with ileal involvement of more than 25
      cm, both weight and height for age are very low at less than the fifth
      percentile, except for one patient whose side patch was at the right colon. One
      patient still needs parenteral nutritional support. Severe iron deficiency
      anemia, low level of B12, and growth retardation are apparent in the patients
      with total colonic aganglionosis with ileal involvement. Colonic side-to-side
      anastomosis does not substitute for the loss of terminal ileum.

PMID- 9021562
TI  - ret Proto-oncogene product is a useful marker of lineage determination in the
      development of the enteric nervous system in rats.
AB  - Detailed study of developmental changes in the enteric nervous system is
      necessary to disclose the pathogenesis of Hirschsprung's and allied disease, some
      of which have hypoplastic ganglia. Therefore experiments were undertaken to study
      the fate of neural crest cells that develop in the rat gut during ontogeny. A
      polyclonal antibody against ret proto-oncogene product (c-Ret protein) and
      various monoclonal antibodies against neural markers (tyrosine hydroxylase,
      dopamine beta hydroxylase, microtubule-associated protein 5, microtubule
      associated protein 2 and 160-kd neurofilaments) were used to identify neural
      crest-derived cells in rat embryos (10.5 to 15.5 days' gestation) and adult rats
      using a double immunostaining method. C-Ret protein was an early marker of
      lineage determination in the development of the enteric nervous system (11.5-day
      embryo: E 11.5). C-Ret-positive cells transiently coexpressed tyrosine
      hydroxylase, which also was observed in the vagal crest-derived precursors of
      enteric neurons (days E 11.5 to E 13.5). These cells also coexpressed other
      neural markers in the proximal gut. Expression of neural markers migrated to the
      distal intestine during development. This study found a discrepancy between the
      time when these markers appeared in the cranial and when they appeared in the
      caudal intestine. Tyrosine hydroxylase-positive cells did not appear in the
      postumbilical gut. The formation of the primitive neural network in the entire
      myenteric plexus at day E 15.5 was demonstrated by c-Ret protein. Other neural
      markers were lost or bad decreased immunoreactivity throughout the entire
      intestine of the E 15.5 and adult animals. In conclusion, (1) c-Ret protein is
      one of the earliest markers of lineage determination in the development of the
      enteric nervous system, (2) each neural marker is expressed at its own time and
      differs in spatial developmental lineage, (3) c-Ret protein and other neural
      markers are transiently expressed by a particular group of neural cells during
      the embryonic period, (4) there is a subpopulation of cells that has never
      transiently expressed tyrosine hydroxylase in the postumbilical gut, which may
      have originated from tissue other than the vagal crest, and (5) the primitive
      neural network in the myenteric plexus was completed at day E 15.5.

PMID- 9021563
TI  - Surgical strategy for the treatment of pyriform sinus fistula.
AB  - Pyriform sinus fistula recurs when a complete excision of the fistula has not
      been made. As a supportive technique for this radical operation, the authors
      performed an intraoperative endoscopic examination of the pyriform sinus for the
      cannulation or dye injection of the tract in four cases. In three cases, the
      sinuses were relatively long and ran outside the thyroid cartilage. The
      cannulation of the tract with a guide wire, in these cases, was useful for
      identifying the thin membranous tract. In one of these three cases sinus fistula
      recurred, but a complete excision of the tract was then performed by introducing
      a 10F Nelaton catheter over a guide wire, which allowed for easy handling of the
      remnant tract. In the remaining case, cannulation proved not to be useful because
      the tract was short and ran inside the thyroid cartilage. A short tract embedded
      within the inferior constrictor muscle could only be found through careful
      observation after repeated dye injections. The proper selection of the optimum
      supportive techniques as described above, are considered to be essential for
      performing a complete excision.

PMID- 9021564
TI  - Use of synaptophysin polyclonal antibody for the rapid intraoperative
      immunohistochemical evaluation of functional bowel disorders.
AB  - Intraoperative biopsies are essential for accurately distinguishing between
      Hirschsprung's disease (HD) and intestinal neuronal dysplasia (IND), and vital
      for determining the extent of abnormal bowel for surgical correction. IND can be
      associated with HD and can be a cause of postoperative complications. Routine
      hematoxylin and eosin (H&E) staining is sometimes inadequate for identification
      of ganglion cells in biopsy specimens and can be the cause of confusion. The
      authors found synaptophysin (SY) to be more specific as an indicator of abnormal
      bowel innervation and invaluable for surgical planning. Twenty patients (15 with
      HD, 3 with IND, and 2 with IND complicating HD) received biopsies
      intraoperatively. There was markedly reduced immunoreactivity (ie, a decreased
      number of SY-positive synapses) seen in the intestinal smooth muscle layers of
      transitional, aganglionic, and IND bowel segments, whereas immunoreactive
      synapses were abundantly present in the smooth muscle layers of ganglionic colon
      in HD. SY immunoreactivity also showed ganglion cells and hypertrophic nerve
      trunks clearly. Rapid SY staining is a simple and consistently reliable method
      for the intraoperative evaluation of the distribution of synapses in myenteric
      plexuses as well as smooth muscle layers.

PMID- 9021565
TI  - Hyaluronic acid of wound fluid in adult and fetal rabbits.
AB  - Fetal wound healing proceeds without fibrosis or scar formation in contrast to
      adult wound healing. The mechanisms responsible for this remarkable process are
      mediated in part through a fetal wound extracellular matrix rich in hyaluronic
      acid (HA). Polyvinylalcohol sponge (PVA) wound implants were placed
      pervertebrally at 24 days' gestation in fetal (N = 118) rabbits and in adult (N =
      44) rabbits, and then harvested at 1, 2, 3, 4, 5, and 7 days postwounding. To
      analyze the fetal and adult wound matrix, the HA concentration of wound fluid
      within the PVA sponge was quantitated using a newly developed assay. A
      significantly increased (P < .05) HA deposition on days 1 through 7 in the fetal
      wounds was found compared with the adult wound. These observations may suggest an
      important physiologic role in fetal wound healing by providing a more fluid and
      malleable matrix. These results, coupled with earlier findings of the lack of an
      acute inflammatory response in the fetus, further support the hypothesis that
      fetal response to injury is significantly different from adult response in this
      prescience of an implanted PVA sponge.

PMID- 9021566
TI  - Congenital malformations of the lung and mediastinum--a quarter century of
      experience from a single institution.
AB  - Congenital malformations of the lung are rare and vary widely in their
      presentation and severity. The authors reviewed 25 years of experience with
      specific reference to diagnosis, treatment, and outcome. From July 1970 to June
      1995, 70 patients were diagnosed with congenital malformations of the lung, which
      included sequestration (n = 20), foregut anomalies (n = 20), congenital lobar
      emphysema (CLE; n = 10), congenital cystic adenomatoid malformation (CCAM; n =
      5), benign lung cysts (n = 6), lung aplasia/ hypoplasia (n = 4), and other
      miscellaneous disorders (n = 5). All patients with pulmonary hypoplasia presented
      at birth. With the exception of one patient, infants with CCAM and CLE presented
      before 5 months of age. All other patients presented from birth to 16 years of
      age. A prenatal diagnosis was accurate in two patients. Although prompt surgical
      management is the rule, the exceptions were children with bilateral lung
      involvement. Corrective surgery was delayed in some patients in whom extended
      respiratory support was required or in whom the delay led to an increase in
      pulmonary reserve. Extracorporeal membrane oxygenation (ECMO) was used in two
      patients pre- and postoperatively to manage persistent pulmonary hypertension.
      This review, representing the largest series of congenital lung lesions, showed
      that (1) prenatal diagnosis is useful but generally does not change the outcome;
      (2) computerized tomography (CT) is the optimum postnatal diagnostic imaging
      modality if chest radiography is not definitive; (3) ECMO can be an adjunct in
      treating associated pulmonary hypertension; (4) pulmonary resection (lobectomy)
      is the surgical procedure of choice for most lesions; (5) expected survival is
      good; and (6) pulmonary hypertension is the most common cause of mortality.

PMID- 9021567
TI  - Pulmonary artery band migration producing endobronchial obstruction.
AB  - Pulmonary artery banding is used in infants to temporarily control excessive
      pulmonary blood flow. There are reports of band migration including intact bands
      eroding through the pulmonary artery. The patient presented here had
      bronchiectasis and eventual destruction of his right middle and lower lobes 5
      years after pulmonary artery banding and subsequent definitive cardiac corrective
      surgery. After undergoing a right middle and lower lobectomy, recurring
      postoperative respiratory distress prompted repeat bronchoscopy where the
      original pulmonary artery band was identified and removed. It is hypothesized
      that this band migrated through the pulmonary artery and into the
      tracheobronchial tree where it led to obstruction and subsequent destruction of
      the right middle and lower lobes. Awareness of this potential complication is
      important for pediatric surgeons who so often care for patients with a past
      history of cardiac surgery.

PMID- 9021568
TI  - A shape memory airway stent for tracheobronchomalacia in children: an
      experimental and clinical study.
AB  - The authors have designed a coil airway stent using a thermal shape-memory
      titanium-nickel alloy (SMA) to relieve airway collapse in children. A
      characteristic of alloy allowed the stent to be enclosed in the thin introducer
      tube and to position it bronchoscopically in the collapsed airway. When the stent
      is warmed to 37 to 40 degrees C, it expands to the memorized diameter and stents
      the airway. In eight rabbits, an experimental model of potentially fatal
      tracheomalacia was created by fracturing the tracheal cartilages. The stents of 6
      mm in diameter and 15 mm in length were placed, and then the stents were
      recovered to their original shape within 1 minute. All rabbits except one showed
      no respiratory symptoms during the follow-up period. Results of bronchoscopy
      performed 6 and 10 months after implantation showed satisfactory patency of the
      trachea. The rabbits were killed for histological evaluation 6 to 28 months after
      implantation. The specimens showed little proliferation of granulation and no
      dislodgement of the stents. This procedure was attempted in two children who had
      severe bronchomalacia. One 5-year-old patient underwent implantation with a stent
      of 5 mm in diameter and 25 mm in length into the left main bronchus. The patient
      was relieved from apneic attacks. The stent was removed 2 years after
      implantation after a remarkable improvement of ventilation. The other patient
      with left bronchomalacia, age 1 year 2 months, underwent implantation with a 5-mm
      x 20-mm stent. The animal experiment and clinical experience indicated that (1)
      this stent can be easily inserted and removed bronchoscopically, (2) the stent
      has good tissue compatibility and little interference of mucociliary function,
      and (3) the SMA stent is a promising therapeutic adjunct in the management of
      children with severe tracheobronchomalacia.

PMID- 9021569
TI  - Experience in tracheobronchial reconstruction with a costal cartilage graft for
      congenital tracheal stenosis.
AB  - Although successful surgical management of congenital tracheal stenosis has been
      reported, it is still controversial as to the best operative procedure. Eleven
      infants with congenital tracheal stenosis were evaluated to confirm the efficacy
      of tracheobronchial reconstruction with costal cartilage graft. Symptoms ranged
      from recurrent respiratory infection to severe respiratory failure. All infants
      had other congenital anomalies in addition to tracheal stenosis. Notably, five
      infants had pulmonary artery sling and four infants had patent ductus arteriosus.
      Definitive diagnosis was made by bronchoscopy, results of which showed complete
      tracheal rings in all patients with severely compromised tracheobronchial lumens.
      Five infants had elongated stenosis involving nearly the whole length of the
      trachea, and five infants had segmental stenosis involving nearly one half the
      length of the trachea. One infant had bilateral stenosis of the main bronchi.
      Early experience included two deaths from problems related to the repair. The
      involvement of the carina and the distal portion of the trachea was associated
      with increased complications and a higher mortality rate. Currently, our
      preferred technique facilitated by extracorporeal membrane oxygenation (ECMO)
      includes carinal reconstruction with a thin-wall intraluminal stent. Bronchoscopy
      is essential for accurate intraoperative incision of the trachea, post-operative
      airway management for several weeks, and removal of the intraluminal stent.

PMID- 9021570
TI  - Currarino triad: anorectal malformation, sacral bony abnormality, and presacral
      mass--a review of 11 cases.
AB  - Currarino et al, in 1981, described an association of a congenital anorectal
      stenosis, or another type of low anorectal malformation, an anterior sacral
      defect, and presacral mass. Eleven patients with this anomaly were treated at the
      Department of Pediatric Surgery, Seoul National University Children's Hospital
      from 1984 to 1995. Among these patients, low-type imperforate anus (IA) was seen
      in three cases and anorectal stenosis was present in eight cases. Presacral
      masses included seven teratomas, two meningoceles, one dermoid cyst, and one
      enteric cyst with dermoid cyst. All had a deformed sacrum. Among the eight with
      anorectal stenoses, posterior sagittal anorectoplasty (PSARP) with diverting
      colostomy was performed in seven cases, and repeated rectal dilatation was
      performed in one case. Among the three low-type IA, anoplasty was performed in
      two cases and PSARP was performed in one case. Although PSARP is a safe and
      satisfactory method facilitating the excision of the presacral mass, in
      meningoceles the repair should be performed before correction of anorectal
      malformation because of the risk of meningitis that can occur when surgeries are
      done simultaneously. In two cases, untethering of a tethered spinal cord was
      performed. All patients are continent. Because the incidence of Currarino triad
      is high when there is an anorectal stenosis (38% in the present series), the
      Currarino triad should be suspected in anorectal stenosis. Magnetic resonance
      imaging is a preferred diagnostic method because the incidence of association of
      tethered cord in this triad is high (18% in the present series).

PMID- 9021571
TI  - Pudendal-thigh flap vaginoplasty in the reconstruction of genital anomalies.
AB  - Children with abnormal genitalia associated with intersex anomalies or cloacal
      malformations require vaginal reconstruction. Although many procedures using skin
      grafts, skin flaps, and intestinal segments have been described, they all have
      disadvantages. In the present study 12 patients with genital defects who required
      vaginoplasty underwent surgery using a new technique using bilateral pudendal
      thigh flaps based on the posterior labial artery. There were six patients with
      congenital adrenal hyperplasia (CAH), three with vaginal atresia, two with
      cloacal deformities, and one with testicular feminizing syndrome. Four of the CAH
      patients and the two with cloaca underwent vaginoplasty as second-stage
      procedures. All other cases were treated with one-stage operations. This method
      of vaginoplasty can be combined with correction of other associated
      abnormalities, and it has proved to be simple and reliable with satisfactory
      functional and cosmetic results.

PMID- 9021572
TI  - Silo formation without suturing in gastroschisis: use of Steridrape for delayed
      repair.
AB  - Although primary repair is preferred for gastroschisis, this cannot be performed
      in many patients because of the visceroabdominal disproportion or other
      accompanying conditions. Several prosthetic materials are used for a silo or
      patch. When prosthetics are used, staged operations are necessary and infection
      is an inherent problem. However, these problems can be avoided by using
      Steridrape for a silo without suturing. The authors used the Steridrape to create
      a covering for two patients. The eviscerated bowel was irrigated and the
      abdominal wall was cleansed. A sheet of Steridrape was attached onto the
      abdominal wall and the herniated viscera was wrapped with it. A second sheet was
      applied over the first one. Antibiotics were administered and parenteral
      nutrition was started. The Steridrape covering was changed twice a week. In 1
      week the edema subsided remarkably and in 2 weeks the bowel had an almost normal
      appearance except for hyperemic serosa. Primary repair was performed on the 19th
      hospital day in patient 1, the 14th day in patient 2. Oral feeding was started 7
      days after repair in patient 1, and 22 days after repair in patient 2. Patient 2
      developed aspiration pneumonia during transport. Discharge was on the 18th day
      after surgery in patient 1 and the 50th day in patient 2. The patients are now 18
      months and 14 months old, respectively, and are doing well. Steridrape
      application in gastroschisis is economical, easy to perform, and is a better
      method to use when transporting the patient. It also facilitates drainage of
      purulent exudate, and allows the bowel to be inspected easily. This method has
      proved useful in treating two patients with gastroschisis.

PMID- 9021573
TI  - Clinical application of minimal residual neuroblastoma cell detection by reverse
      transcriptase-polymerase chain reaction.
AB  - The highly sensitive method to detect neuroblastoma (NB) cells using reverse
      transcriptase polymerase chain reaction (RT-PCR) was applied in the practical
      clinics, and its efficacy was assessed in the present study. Human tyrosine
      hydroxylase (TH), a rate-limiting enzyme in the catecholamine biosynthesis, was
      used as the marker for NB cells, and the expression of THmRNA was examined in 13
      samples (four peripheral blood and nine bone marrow) harvested from seven
      patients (four with stage IV, one with stage III, two with stage II) using RT-PCR
      with our original primers. The positive signals for NB cells were detected in
      four samples (one peripheral blood and three bone marrow) by the PCR method, but
      were undetectable by the conventional histological examinations. In the present
      series, a case that showed a positive signal for NB cells in the peripheral blood
      showed a remarkably unfavorable clinical course, indicating that the circulating
      NB cells detected by the PCR method can be a sign of the progressively advanced
      NB, and may define a new prognostic factor suggesting higher risk. In another
      case, the PCR detection for the residual NB cells in the bone marrow provided
      important supporting evidence to determine the necessity of the additional
      chemotherapy and the suitable timing for bone marrow transplantation. This
      detection also guaranteed the safety of the bone marrow for transplantation. The
      PCR method was considered to be very beneficial in the selected cases. However,
      some problems such as the false-negative results in the negative urinary
      vanillylmandelic acid secretor were also highlighted in the present study.

PMID- 9021574
TI  - The death of a child--the parent's perspective and advice.
AB  - Recognizing the grief of parents after they have lost a child is an integral part
      of the practice of pediatric surgery. Parents who have experienced the loss of a
      child suggest the following: (1) The feelings associated with the loss of a child
      are not understandable unless you have lost a child of your own. (2) If you have
      not experienced the loss of your own child you should not state "I understand."
      You can't (3) The death of a child places stress on the marriage. (4) Many
      marriages do not survive. If the marriage does survive it becomes stronger than
      before the child's death. (5) During the recovery the parents see themselves as
      "different people." (6) Mothers and fathers react to the death differently. (7)
      Some parents have initiated new, beneficial projects that are in some way related
      to the child's death. (8) Parents react adversely to "pat" explanations and
      platitudes. (9) Parents want their friends and relatives to remain available.
      (10) The dead child should remain as an integral part of the family and no
      attempt should be made to "forget." (11) The self-help group that is referred to
      most frequently is "The Compassionate Friends, Inc.," with headquarters in Oak
      Brook, Illinois.

PMID- 9021575
TI  - Biochemical and morphological changes in the liver during isolated liver
      perfusion with double bypass using automatic blood pumps.
AB  - Isolated organ perfusion is used in clinical practice for chemotherapy in adults
      with malignant tumors. However, it has not been performed in children because of
      the size mismatch with the adult circuits. The authors have previously studied
      isolated liver perfusion in small animals using the self-regulating
      extracorporeal membrane oxygenation circuit. The present study was designed to
      investigate the biochemical and morphological changes in the liver during
      isolated liver perfusion with double bypass using automatic blood pumps. Isolated
      liver perfusion was performed with bypass between the hepatic and portal veins in
      seven weanling Yorkshire swine weighing 8.2 to 12.2 kg, at a flow rate of 20
      mL/min/kg for up to 4 hours. Venous blood from the intestine and lower body was
      bypassed to the superior vena cava. As a result, perfusate glutamic pyruvic
      transaminase and lactate concentrations did not change during liver perfusion. On
      gross inspection, the surface of the liver was mottled. Microscopically, normal
      histology of the hepatic parenchyma and portal tract structures was preserved.
      Transmission electron microscopy showed no gross structural abnormalities in most
      of the hepatocytes for up to 4 hours. However, swelling of the mitochondria and
      smooth endoplasmic reticulum was seen occasionally in a very small number of the
      hepatocytes after more than 3 hours of perfusion. Glycogen granules decreased
      with time in some animals. Isolated liver perfusion at 20 mL/min/kg of perfusion
      flow can be performed safely for up to 4 hours with nearly intact hepatocellular
      function and morphology.

PMID- 9021577
TI  - Surgical treatment of testicular trauma: effects on fertility and testicular
      histology.
AB  - Unilateral testicular trauma in the postpubertal male can lead to alterations in
      semen analysis, but it is not clear what effect this has on fertility. To better
      understand how surgical treatment of testicular trauma affects both fertility and
      testicular histology the following study was performed. Eighty postpubertal Lewis
      rats were divided into eight equal groups with one group serving as a control. In
      the 70 remaining rats the left testicle was subjected to blunt or penetrating
      injury. The testicles were either left untreated, were removed, or were repaired
      with sutures or mesh before being returned to the scrotum. Following recovery,
      each male was allowed to mate to determine fertility. Fertility rates were
      significantly lower in all postinjury groups except the postinjury orchiectomy
      group. Histological analyses showed nonspecific inflammation, smaller tubules,
      and impaired spermatogenesis in all postinjury testicles regardless of the type
      of treatment. Contralateral testicles had no evidence of autoimmune injury and
      were essentially identical to the control group. In the postpubertal Lewis rat,
      unilateral testicular trauma leads to impaired fertility unless the injured
      testicle is removed soon after the injury. Various methods of repairing the
      injury did not improve fertility. In spite of the impaired fertility, the
      contralateral testicle appears histologically normal.

PMID- 9021576
TI  - Liver transplantation in children: the experience of Queen Mary Hospital, Hong
      Kong.
AB  - Seven living-related liver transplants (LRLT) and two reduced-size liver
      transplants (RSLT) were performed on eight children who suffered from end-stage
      liver disease, having previously undergone one to three abdominal operations.
      Their ages at initial transplantation ranged from 8 months to 11 years (mean 35
      months, median 12 months). Excluding the two older children aged 7 and 11 years,
      respectively, the rest of the children weighed 6 to 9.5 kg (mean 7.3 kg) at the
      time of the initial transplantation. Seven left lateral segments (S2 + 3) and two
      left lobes (S2 + 3 + 4) were used; of these the smallest graft had a graft-to
      recipient body weight ratio of 0.9%. The volunteer living donors were four
      mothers, two fathers and one sister who were selected after medical and
      psychiatric evaluations, and their suitability was confirmed by hematological,
      biochemical, and radiological criteria. During a follow-up period of 3 to 30
      months, all eight children are alive and well with normal liver function, one of
      them having undergone a retransplant LRLT because of hepatitis of undetermined
      etiology following a RSLT 1.5 years earlier. All seven donors had an uneventful
      postoperative course and were discharged on day 4 to 7 postoperatively. They have
      all resumed normal day-to-day activities. There were no complications in the
      donor group. A variety of complications occurred in the recipients, all of which
      were overcome. Operating microscope was used to perform all the arterial
      anastomoses using microvascular techniques. This method has proven to be a major
      factor in preventing arterial thrombosis even with the smallest of arterial
      anastomosis where a 1.5-mm diameter recipient artery was anastomosed to a 2.5-mm
      diameter donor hepatic artery.

PMID- 9021578
TI  - Brain concussion produces transient hypokalemia in children.
AB  - Hyperglycemia and hypokalemia caused by catecholamine discharge have been
      reported to occur in patients after severe head trauma. The aim of this
      prospective study was to evaluate whether a similar neuroendocrine and metabolic
      response is found in children after minor head trauma such as brain concussion
      (Glasgow Coma Scale (GCS) > or = 13). One hundred fifty patients aged 2 to 14
      years (average, 6 years) were divided into three groups (n = 50 in each group).
      Group 1 included patients admitted to the emergency department for brain
      concussion (Glasgow Coma Scale (GCS) > or = 13); group 2 included patients
      admitted for fractures of long bones without head injury; and group 3 were
      control patients electively admitted for hernia repair. All patients had complete
      physical and neurological examinations. Complete blood count and blood chemistry
      were obtained on admission. All blood tests were repeated at 6, 12, and 24 hours
      in patients belonging to group 1. An electrocardiogram was obtained in selected
      patients and catecholamine levels were measured in some patients. Statistical
      analysis was performed using analysis of variance (ANOVA). Serum potassium and
      sodium levels in patients with brain concussion (group 1) were 3.6 +/- 0.6 and
      136 +/- 3 mEq/L, respectively and were significantly lower (P < 0.01) than those
      in patients belonging to group 2, 4 +/- 0.4 and 138 +/- 3, respectively, and the
      controls (group 3), 4.2 +/- 0.5 and 140 +/- 2, respectively. Serum glucose level
      was 124 +/- 34 and 118 +/- 32 mg% in groups 1 and 2 and was significantly higher
      than that of the controls (group 3), 90 +/- 23 mg%. There was no correlation
      between serum electrolytes and GCS. No electrocardiogram changes or elevation of
      serum catecholamines were found. Hypokalemia resolved spontaneously within 24
      hours. All patients recovered without neurological sequalae. Transient
      hypokalemia frequently occurs in children even with minor head trauma. This
      hypokalemia resolves spontaneously, without treatment and within 24 hours.

PMID- 9021579
TI  - Digestive tract disorders associated with asplenia/polysplenia syndrome.
AB  - The authors reviewed experience gained over a 20-year period of asplenia or
      polysplenia syndrome, focusing on patients with associated digestive tract
      disorders (DTDs). Eleven of 27 patients (40%) with asplenia/polysplenia had
      associated DTDs. The DTDs comprised malrotation of the intestine in nine, both
      preduodenal portal vein and gastric volvulus in three, esophageal hiatal hernia
      in two, and biliary atresia in one. Laparotomy was carried out on four patients
      with symptoms of acute bowel obstruction and on one patient with biliary atresia.
      One patient with both malrotation and gastric volvulus, and another with only
      associated malrotation survived. Nine patients died, eight of cardiac
      insufficiency and one because of hepatic insufficiency. When infants are
      diagnosed with heterotaxia, they should be examined for other combined DTDs,
      because they may have a chance for survival if they undergo surgery when their
      condition is still stable.

PMID- 9021580
TI  - Mortality among infants with high-risk congenital diaphragmatic hernia in
      Singapore.
AB  - Several factors suggested to predict mortality in congenital diaphragmatic hernia
      (CDH) have not always been applicable in different centers. A retrospective
      review was conducted of 19 consecutive neonates in Singapore in whom CDH was
      diagnosed within 12 hours of birth to identify factors associated with mortality.
      Of the 19 cases, 15 (79%) were diagnosed using antenatal ultrasonography. Eight
      (42%) underwent primary repair at a median age of 23 hours (range, 12 to 50
      hours). Of the 19 infants, 15 died (mortality rate, 79%). Survivors until
      hospital discharge were compared with nonsurvivors. Antenatal diagnosis and
      stomach position in left-sided defects had no effect on outcome, although
      polyhydramnios tended to be associated with nonsurvival. Significant postnatal
      factors associated with mortality included a low arterial pH level, low initial
      arterial-alveolar oxygen ratio, high initial alveolar-arterial oxygen gradient,
      as well as high oxygenation and ventilation indices. These results reflect
      difficulty in oxygenation because of pulmonary hypoplasia despite evidence of
      adequate ventilation. There was no difference between survivors and nonsurvivors
      in either their initial or best postductal blood gases. The "Bohn quadrants" did
      not aid in predicting survival of infants who underwent repair because all eight
      such infants had best postductal carbon dioxide values of less than 40 mm Hg and
      ventilation indices of less than 1,000. Yet only four (50%) survived until
      hospital discharge. Large-scale evaluation of these factors may be required in
      the future to demonstrate their validity and reliability because of changing
      management strategies for CDH.

PMID- 9021581
TI  - Nitric oxide inhalation therapy for an infant with persistent pulmonary
      hypertension caused by misalignment of pulmonary veins with alveolar capillary
      dysplasia.
AB  - Misalignment of pulmonary veins with alveolar capillary dysplasia (MPV) has been
      reported to be a rare cause of persistent pulmonary hypertension of the newborn
      (PPHN) and to be fatal despite extracorporeal membrane oxygenation (ECMO). A full
      term female neonate with PPHN was brought to the hospital for ECMO therapy at 2
      days of age. On the 14th day of life, she was extubated early after the second
      run of ECMO, and underwent nitric oxide (NO) inhalation therapy in the incubator.
      She died of catheter-related sepsis on the 61st day of life. After autopsy
      findings revealed MPV, the longest survival with this disease was documented. NO
      inhalation therapy in the incubator may provide time for lung transplantation.

PMID- 9021582
TI  - Congenital right diaphragmatic hernias through posterolateral and anterolateral
      defects associated with extralobar pulmonary sequestration: a case report.
AB  - Multiple diaphragmatic hernias in the unilateral diaphragm are extremely rare.
      The authors report a neonate with diaphragmatic hernias through two defects in
      the right diaphragm: a posterolateral defect without a hernia sac and an
      anterolateral defect with one. After excision of the anterolateral hernia sac,
      each defect was closed. Histology studies showed extralobar pulmonary
      sequestration in the removed hernia sac. The presence of sequestrated pulmonary
      tissue indicates the possibility of interference with the closure of the
      pleuroperitoneal canal and muscularization in the diaphragm, which may result in
      multiple defects.

PMID- 9021583
TI  - Tracheal rupture after blunt chest trauma in a child.
AB  - Blunt traumatic tracheal rupture is a life-threatening injury. The authors report
      on a 14-year-old boy who suffered such an injury in a road accident, underwent
      surgery immediately, and survived. The relevant literature is reviewed.

PMID- 9021584
TI  - Childhood bronchial mucoepidermoid tumors.
AB  - A very rare case of a childhood bronchial mucoepidermoid tumor is presented. A 4
      year-old girl was hospitalized with prolonged pneumonia. Computed tomography of
      the chest showed a tumor with calcifications in the right upper lobe.
      Subsequently, the patient underwent right upper lobectomy. Histologically, the
      tumor was a low-grade mucoepidermoid tumor originating from the bronchus. Three
      years postoperatively there has been no evidence of disease. A review of the
      literature indicates that 30 cases of bronchial mucoepidermoid tumors in children
      have been reported. Symptoms result from associated bronchial obstruction.
      Children with recurrent or prolonged pneumonia should undergo aggressive
      diagnostic investigation by chest tomography or bronchoscopy. Appropriate therapy
      for childhood bronchial mucoepidermoid tumor is total resection of the lesion
      while sacrificing as little of the normal lung tissue as possible.

PMID- 9021585
TI  - Pyocolpos: diagnosis and treatment.
AB  - Pyocolpos is a rare complication of hydrocolpos. Hydrocolpos usually presents
      during adolescence and is associated with an imperforate hymen. The following is
      a case of a 3-month-old girl with pyocolpos. Her history was significant for a
      urinary tract infection (UTI) at 7 weeks of age. The authors believe that her UTI
      was caused by urinary retention secondary to hydrocolpos. A complete evaluation
      may have prevented the complication of pyocolpos.

PMID- 9021586
TI  - Caval thrombectomy for severe staphylococcal osteomyelitis.
AB  - Two children are presented in whom thrombosis of the inferior vena cava developed
      in association with an acute staphylococcal osteomyelitis. One case involved the
      left femur and the other the left ileum. Both children had diffuse bilateral
      staphylococcal pneumonia from presumed septic embolization. There were close
      similarities between their illness and management, except that the child who
      survived underwent a caval thrombectomy in the acute phase of her illness. It is
      hypothesized that the thrombectomy played an important role in her recovery.

PMID- 9021587
TI  - Highly differentiated teratoma and fetus-in-fetu: a single pathology?
AB  - A case of sacrococcygeal teratoma is presented with characteristics of fetus-in
      fetu. This pseudo-fetus presented a rudimentary single cavity heart, which beat
      at a different rate to that of the affected infant. X-ray examination showed no
      spinal column. This case confirms that fetus in fetu can be a remarkably complex,
      well-differentiated, highly organized teratoma.

PMID- 9021588
TI  - Colonic volvulus: a rare presentation of Hirschsprung's disease.
AB  - Although rare, patients with Hirschsprung's disease (HD) may be admitted with
      colonic volvulus. Among 302 patients with HD two patients were admitted with
      colonic volvulus (0.66%). Involved segments were cecum and sigmoid colon. During
      the same period, 11 patients including those with HD were diagnosed with colonic
      volvulus. An aganglionic segment below sigmoid colon, and a freely mobile
      mesosigmoid seem to be the cause of sigmoid volvulus. However, extension of
      aganglionosis above the sigmoid colon in addition to anatomic tendency seems to
      result in volvulus of proximal segments. Because HD has been associated with
      colonic volvulus, children who present with colonic volvulus should be suspect
      for underlying HD.

PMID- 9021589
TI  - Multicystic kidney in siblings.
AB  - Two siblings (one girl and one boy), with a left multicystic kidney in whom a
      renal abnormality had been recognized prenatally, are reported. A large renal
      mass was present in both patients and the second sibling also had hypertension.
      Early surgical resection was carried out with satisfactory clinical progress and
      resolution of the hypertension. Multicystic kidney is considered a developmental
      abnormality with a sporadic incidence. These cases and other reports of familial
      incidence in the literature indicate that there may also be a genetic basis for
      the abnormality.

PMID- 9021590
TI  - Granulocytic sarcoma of the scapula: an unusual presentation of acute
      myeloblastic leukemia.
AB  - The unusual presentation of acute myeloblastic leukemia as a scapular
      granulocytic sarcoma in an infant without systemic manifestations is reported for
      the first time. Granulocytic sarcoma as a presentation of leukemia should be
      considered in the differential diagnosis of scapular masses during childhood.
      Surgery is limited to obtain sufficient tissue for histopathologic diagnosis.

PMID- 9021591
TI  - Appendiceal perforation: a potentially lethal initial mode of presentation of
      Hirschsprung's disease.
AB  - In Hacettepe University Children's Hospital, between 1976 and 1993 two patients
      among 302 with Hirschsprung's disease were diagnosed with appendiceal perforation
      (AP) at initial admission. Both patients were less than 2 months of age. One of
      them was a boy with total colonic aganglionosis and the latter a girl with long
      segment disease. In both cases the site of AP was the base, and periappendicitis
      without mucosal involvement was detected. The present cases and review of the
      literature suggest that longer aganglionic segment carries a higher risk of AP.

PMID- 9021592
TI  - Emergency transjugular intrahepatic portosystemic shunt (TIPS) in an infant: a
      case report.
AB  - Since the first successful report regarding the feasibility of transjugular
      intrahepatic portosystemic shunt (TIPS) as an alternative to surgical
      decompression of portal hypertension, this method has been used extensively as a
      temporizing measure in controlling refractory variceal bleeding before liver
      transplantation in adults with cirrhosis. There are few reports of TIPS in
      pediatric patients because variceal bleeding in most of these patients can often
      be managed conservatively without invasive intervention. Recently, successful use
      of TIPS to treat complications of portal hypertension has been described in two
      children ages 10 and 13. To our knowledge, there are no reports of TIPS used in
      infants under the age of 1 year. The authors report a case in which TIPS was used
      to successfully control variceal bleeding in a 10-month-old infant before
      consideration for hepatic transplantation.

PMID- 9021593
TI  - Mesenteric neurofibroma in von Recklinghausen's disease.
AB  - The authors report the case of a 6-year-old boy admitted for surgical removal of
      a 5- x 4-cm neurofibroma over the left wrist. On routine clinical examination a
      mobile firm, nodular, central abdominal mass was discovered. At laparotomy a
      tumor (measuring 7 x 5 x 3 cm) arising from the ileal mesentery was found.
      Complete excision of the mass together with a segment of ileum, followed by end
      to-end bowel anastomosis was performed. Histological examination showed that the
      main elements of the mass consisted of wavy, long-spindled cells that crossed
      irregularly (pallisading negative). Special stains and immunocytochemistry for S
      100 protein confirmed the mass to be a neurofibroma of the mesentery. The patient
      had an uneventful postoperative course and no signs of recurrence or fresh tumor
      have been recognized in the 4 years since his operation.

PMID- 9021620
TI  - Wound healing and tissue repair of the surgical amputation of limbs.

PMID- 9021621
TI  - Design and pilot testing of the DVA/Seattle Footwear System for diabetic patients
      with foot insensitivity.
AB  - Clinical epidemiology studies suggest the majority of lower limb amputations were
      preceded by a minor traumatic event, often footwear-related, and lower limb
      ulcers. To reduce foot trauma and ulcers, the diabetic patient with foot
      insensitivity has unique footwear needs. To address these needs for patients not
      requiring custom shoes, the DVA/Seattle Footwear System was developed. The six
      components of this system include: 1) a specially designed shoe last based on the
      geometry of the diabetic foot and research findings on foot regions at highest
      risk of ulceration, 2) a depth-inlay shoe, "Custom Stride by PRS," designed to be
      paired with either a custom-fabricated cork insole or a preformed polyurethane
      insole, 3) a laser digitizing system that captures 3-D plantar foot contours, 4)
      DVA/Seattle ShapeMaker software adaptation for modifying plantar surface contours
      and applying free-form and template modifications to increase or relieve loading,
      5) software that translates files into code used by a milling machine to define
      the cutting path and carve cork blockers into custom insoles, and 6) a preformed
      polyurethane insole thicker than a typical insole to accommodate the extra volume
      and the interior dimensions of the shoe. A 6-month pilot cross-over trial of 24
      diabetic male veterans without prior foot ulcers was conducted to determine the
      feasibility of producing, and the safety of wearing, these depthinlay shoes and
      both types of insoles. During the first 4 weeks, patients were assigned to the
      study shoes and one type of insole. During the next 4 weeks, they wore the other
      type of insole, and during the final 4 months, they chose which pair of insoles
      to wear with the study shoes. Over 150 person-months of footwear observation
      revealed no breaks in the cutaneous barrier with use of either cork or
      polyurethane insoles and the study shoes. Patient compliance with the footwear
      was 88%. Patients were highly satisfied with the appearance, stability, and
      comfort of the shoes and the comfort of both types of insole. However, 75% of the
      patients noted that the study shoes felt heavier than their customary shoes.
      Further research is needed to determine the long-term effectiveness of footwear
      in prevention of foot ulcers in the population at highest risk for diabetic
      reulceration and amputation.

PMID- 9021622
TI  - Stair ambulation in persons with transtibial amputation: an analysis of the
      Seattle LightFoot.
AB  - The purpose of this study was to document gait patterns in a group of individuals
      with transtibial amputations (TTA) during stair ambulation, and to identify the
      functional limitations associated with this task. Ten persons with TTA fitted
      with a Seattle LightFoot prosthetic component, and 14 nondisabled subjects
      participated in this study. Electromyographic activity (EMG) of the vastus
      lateralis (VL), rectus femoris (RF), gluteus maximus (GMAX), semimembranosus
      (SMEMB), biceps femoris long head (BFLH), and biceps femoris short head (BFSH)
      was assessed using indwelling wire electrodes during ascending and descending
      stairs. Lower limb kinematics (VICON) and stride characteristics (Footswitch
      Stride Analyzer System) also were collected. Stride characteristics revealed that
      those with TTA had a significantly slower rate of stair ambulation and
      demonstrated stance phase asymmetry between limbs compared to the nondisabled.
      Kinematic analysis determined significant limitations in prosthetic ankle motion,
      which necessitated compensatory functions at the hip and knee to accomplish stair
      ascent and descent and resulted in significantly greater muscular effort
      (increased EMG intensity and duration) compared to nondisabled.

PMID- 9021623
TI  - Interface pressures and shear stresses at thirteen socket sites on two persons
      with transtibial amputation.
AB  - Residual limb/prosthetic socket interface pressures and shear stresses were
      measured at 13 sites on two subjects with unilateral transtibial amputation (TTA)
      using total-contact patellar-tendon-bearing prostheses. Maximal interface
      stresses during stance phase for each of 13 transducer sites were determined,
      then means for all steps calculated. Maximal pressure and resultant shear stress
      during stance phase were shown at anterior distal or mid-limb sites and the
      maxima occurred during the first 50% of stance phase. Anterior medial and lateral
      proximal sites showed their greatest pressure during the second 50%. At lateral
      mid-limb and popliteal fossa sites, resultant shear stress directions suggest
      that soft tissue was displaced toward the socket brim during weight-bearing.
      Results also suggest that skin across the distal tibial crest was in tension at
      the times of the first and second peaks in the shank axial force-time curve in
      all sessions. Significant difference (p < 0.05) in maximal stresses between
      sessions conducted > 3 weeks apart were apparent for both subjects.

PMID- 9021624
TI  - Noninvasive quantification of muscle oxygen in subjects with and without
      claudication.
AB  - The disabling pain of intermittent claudication (IC) arises from oxygen
      deprivation in the lower limbs during walking. Measurement of the oxygen
      deficiency within the limb tissue now appears possible with recently expanded
      understanding of the photon transport through tissue for photons in the visible
      and near infrared range. Noninvasive measurement consists of preferentially
      measuring photons that have traveled more deeply into limb tissues and that,
      therefore, may reach locations of ischemic tissue. Oxygen measurements appear to
      be possible up to a depth approaching 1.5 cm beneath the surface of the skin. The
      present study reports on data acquired from the limbs of 11 subjects with IC and
      12 subjects without IC. The subjects with IC are patients with clinical findings
      of claudication based upon segmental Doppler pressure profiles and subjective
      reports by the patient of pain during exercise. The subjects without IC are
      individuals with no prior history of ischemic vascular disease. The results
      consist of photon reflectance measurements at red and infrared wavelengths
      (approximately 660 nm and 880 nm respectively) taken before, during, and after
      exercise. Infrared reflectance indices are plotted as well as oxygenation indices
      generated from combining red and infrared reflectances. A compilation of exercise
      data shows responses that are generally consistent with the expected
      physiological responses to mild exercise in subjects with and without IC. We
      anticipate that the findings of this study may lead to an objective noninvasive
      testing procedure for measuring the ischemic and exercise-induced changes in
      muscle oxygenation in the presence of claudication. If the testing of ischemic
      hypoxia continues to show consistency and accuracy in determining the disability
      of the subjects with IC, future studies can more effectively test modes of
      conservative management, such as cessation of smoking, alternative exercise
      regimens, weight loss, and alternative pharmacological agents.

PMID- 9021625
TI  - Analysis of a vertical compliance prosthetic foot.
AB  - Mechanical testing of the Re-Flex VSP Foot was conducted on the pylon alone and
      on the pylon and forefoot system. Values for spring and damping correspond well
      to values reported in the literature for spring and damping of physiological
      limbs. Pylon stiffness was 49.4 kN/m for a 600 N subject and 91.4 kN/m for an 800
      N subject. The vertical stiffness of the pylon and forefoot together was 31.9
      kN/m and 37.8 kN/m, respectively. Gait parameters of two persons with transtibial
      amputation who used vertically compliant feet for walking, jogging in place, and
      curb descent were investigated. Ground reaction forces, vertical trunk movement,
      event timing, and pylon compression were observed. The spring-loaded telescoping
      pylon was immobilized for half the trials. The trials were repeated the following
      week with the vertical compliance feature mobilized. Significant differences in
      vertical trunk motion and timing were found between the prosthetic limb and
      normal limb, as might be expected. Vertical compliance appeared to cause little
      change in gait parameters during normal walking. The largest differences appeared
      during the higher impact events such as fast walking and jogging in place.

PMID- 9021626
TI  - Wheelchair rider injuries: causes and consequences for wheelchair design and
      selection.
AB  - An understanding of adverse incidents and injuries sustained by active wheelchair
      riders, who live and work in the mainstream of society, is needed to improve
      safety via wheelchair design, selection, and configuration. We interviewed 109
      riders who had experienced incidents, in order to identify the causes of
      incidents and injuries they suffered. Participants reported n = 253 incidents
      (53% in powered wheelchairs, 47% manual) occurring within a 5-year period,
      comprised of 106 (42%) "Tips and Falls," 84 (33%) "Component Failures," and 63
      (25%) "Other" events. Sixty-eight (27%) of the incidents caused injuries
      requiring medical attention, including 13 hospitalizations. Direction of Tips and
      Falls was associated with wheelchair type (manual or powered) and with different
      riding surfaces. Aspects of wheelchair stability, particularly the effects of
      wheelchair configuration and of different riding surfaces, are important
      engineering issues affecting wheelchair safety. Interpretation of the results
      highlights wheelchair stability mechanics. Potential design improvements are
      discussed.

PMID- 9021627
TI  - Direct bladder stimulation with suture electrodes promotes voiding in a spinal
      animal model: a technical report.
AB  - To determine the efficacy of a new electrode for direct bladder stimulation, five
      male cats were instrumented during anesthesia. Multistranded, 316LVM, stainless
      steel, wire electrodes were implanted on the bladder wall serosa above the
      trigone area. The electrodes were made with a needle attached to the end that was
      cut off after suturing the electrode in place. Additional instrumentation
      included tubes for pressure recording and filling, and hook electrodes for leg
      and pelvic floor EMG recording. Bladder filling and stimulation studies were
      conducted in tethered animals 1 to 2 weeks following recovery. Chronic studies
      were conducted following recovery in tethered animals. To test these electrodes
      in a spinal cord injury (SCI) model, a T-1 level complete lesion was performed on
      the above instrumented animals. Spinal animals had successful direct bladder
      stimulation that induced active contractions and voiding both before and after
      SCI, but voiding rates were higher more than 2 weeks after SCI and at larger
      initial bladder volumes. Optimum stimulation parameters consisted of 40 pulses
      per second, 300 microseconds to 1 ms pulse duration, a stimulation period of 3 to
      4 s, and 10 to 40 mA. Urethral resistance, indicated by a urethral function
      measure, showed that stimulation had no adverse effect on urethral function, and
      fluoroscopy showed an open membranous urethra during stimulation and voiding. The
      cat has a small penile urethra that is the flow rate controlling zone. The suture
      electrode did not corrode, erode into the bladder, or become dislodged, and
      appears suitable for chronic implantation.

PMID- 9021628
TI  - Instrumented objects for quantitative evaluation of hand grasp.
AB  - Two instrumented objects have been developed for quantitative assessment of
      functional tasks performed with the hand. These objects are useful for assessing
      neuroprosthetic hand grasp systems, and may also be useful in evaluating a
      variety of other upper limb disabilities and rehabilitation techniques. One
      object monitors grasp forced and object orientation during palmar prehension,
      allowing simulation of a drinking task or of manipulating a book. The second
      object monitors grasp force during lateral prehension for simulating eating or
      writing tasks. The two objects provide tools to analyze how a subject uses a hand
      grasp neuroprosthesis to perform activities of daily living. The objects will
      also be useful in comparing different methods of controlling the neuroprosthesis
      and in evaluating future changes in the neuroprosthetic system. Assessment trials
      with these two instrumented objects were performed quickly in an outpatient
      clinic setting.

PMID- 9021629
TI  - Influences of cane length on the stability of stroke patients.
AB  - The purpose of this study was to investigate the influence of cane length on the
      standing and walking stability of stroke patients. Ten stroke patients were used
      as subjects and evaluated by using two different cane lengths based on the
      measurements of the distance from distal wrist crease to the ground (WC cane),
      and the distance from greater trochanter to ground (GT cane). Force plates were
      used to determine the center of pressure (COP). The maximum sways, the total
      travel distances, and the mean travel speeds of the COP were analyzed for each
      patient standing and walking with and without canes. It was found that the total
      travel distance and the mean travel speed of the COP in the medial-lateral (M-L)
      direction were significantly lower when standing with a cane than when standing
      without one. It was also found that the values of these parameters and the
      maximum sways of the COP in both anterior-posterior (A-P) and M-L directions were
      significantly lower when standing with the WC cane than when standing with the GT
      cane. No significant difference was found in the maximum M-L sway, the total
      travel distance, and the mean travel speed of the COP in walking. These results
      suggest that the standing stability of stroke patients is improved by using
      canes, especially by using a WC cane, although no significant influence of using
      canes on the walking stability was detected. Based on the results of this study,
      the vertical distance from the wrist crease to ground is recommended as the
      appropriate cane length for stroke patients.

PMID- 9021630
TI  - Ocular outflow facility with emphasis on neuronal regulation of intraocular
      smooth muscles.

PMID- 9021631
TI  - Phenoxybenzamine discriminates between two distinct populations of histamine H1
      receptors in longitudinal muscle of guinea-pig ileum.
AB  - The longitudinal muscle of guinea-pig ileum was used as a test tissue.
      Progressive (up to 70 min) treatment with phenoxybenzamine (10(-6) M) inhibited
      progressively the response to histamine and progressively decreased the density
      of histamine H1-receptors. However, the 90 min treatment has no further
      significant inhibitory effect on the contractile response and did not decrease
      the density of the receptors. These results suggest that phenoxybenzamine
      discriminates between two distinct populations of H1-receptors. Furthermore, it
      was found that the presence of GTP gamma-S made some populations of H1-receptors
      resistant to phenoxybenzamine and facilitated an interaction of mepyramine with
      H1-receptors.

PMID- 9021632
TI  - Mechanisms of ionic currents involved in suppressive effect of isoprenaline on
      the action potential of guinea-pig vas deferens in normal Krebs solution.
AB  - The effects of beta-adrenoceptor stimulation by isoprenaline (ISO) on action
      potential and membrane current were studied in the guinea-pig vas deferens in
      normal Krebs solution by using a double sucrose gap method. In current-clamp
      experiments, ISO produced the membrane hyperpolarization by reducing the
      resistance and modified the pattern of multi-spike activity elicited by long
      depolarizing currents; an initial spike potential was reduced in the amplitude
      and the rate of rising phases and the slope of diastolic depolarization was
      slowered, leading to a prolongation of the spike discharge interval. In voltage
      clamp experiments, ISO greatly enhanced the late outward K+ current (Ik2) by
      increasing the conductance, but hardly affected the peak outward K+ current
      (Ik1). ISO also reduced the inward Ca2+ current (Ica) by decreasing the
      conductance (ga) as well as by reducing the driving force for Ca2+. While it
      increased the leakage conductance (g1) due to K+ associated with hyperpolarizing
      voltage steps. In the preparations treated with Ca2+ channel blocker such as D
      600, the enhanced effect of ISO on the Ik was still prominent, suggesting that
      Ca2+ and K+ channels appear to be independently regulated during beta
      adrenoceptor stimulation. These results suggest that ISO exerts depressant
      actions on the vas deferens muscle by reduction of the Ica as well as by
      prominent enhancement of the Ik2 via beta-adrenoceptor activation.

PMID- 9021633
TI  - Reflecting on the meaning of success.

PMID- 9021634
TI  - Body composition in clinically stable men with HIV infection.
AB  - Clinically stable HIV-infected men (N = 106) receiving investigational
      antiretrovirals were recruited. Subjects were divided into three HIV disease
      severity groups by CD4+ cell count. Standard measures of body composition were
      assessed, as well as serum measures of visceral protein stores and kilocalorie
      intake. Group 1 subjects (CD4+ T cells < 200) had significantly lower measures of
      body fat as compared with Group 2 (CD4 between 200 and 600) and Group 3 (CD4 >
      600) despite adequate kilocalorie intake. Group 2 and Group 3 were not
      significantly different from each other. Our entire cohort had significantly
      lower muscle mass compared to norms. Our data demonstrate that people with
      advanced HIV disease have reduced muscle and fat.

PMID- 9021635
TI  - Training people with HIV disease for involvement in community planning process:
      Project LEAP. Learning Empowerment Advocacy, Participation.
AB  - Social and political pressure, as well as public health theory, mandate inclusion
      of PLWHIV in community planning and policy development processes. Barriers to
      PLWHIV participation may be cognitive, instrumental, and/or affective. The
      authors report on development, implementation, and initial evaluation of a pilot
      project testing a psychoeducational intervention to increase organizational
      participation by people with HIV. Organizational participation by individual
      increased from a mean of 0.5 organizations at entry to 2.3 at follow-up.
      Evaluation data indicate that increases in self-esteem, self-confidence, and
      specific knowledge, along with demystification of organizational operations,
      networking, and modeling by project staff contributed to the outcome.

PMID- 9021636
TI  - Diagnosing HIV dementia: a retrospective analysis.
AB  - The purpose of this study was to determine the criteria by which the diagnosis of
      HIV dementia was made by providers in a public HIV outpatient clinic and
      hospital, and to evaluate the extent to which the providers' diagnosis confirmed
      or denied the presence of HIV dementia according to CDC recommendations.
      Retrospective chart analysis was conducted detailing symptomology, laboratory
      findings, and social characteristics of 103 HIV-infected patients from Nov 1,
      1990 to Dec 31, 1993. Seventy-eight patients were evaluated by providers and
      given a preliminary HIV dementia diagnosis; 25 patients received no preliminary
      diagnosis. On follow-up, 39 were confirmed diagnosis while 64 patients received
      no follow-up (confirmatory) diagnosis. Inability to pay attention or remember
      details, memory deficit, motor weakness, and mild disorientation were all found
      to be significantly associated with being evaluated by a provider. Substance use
      was prevalent. Inconsistent manner in which HIV-demented patients were identified
      highlights the need for a standardized evaluation of signs and symptoms known to
      be associated with HIV dementia.

PMID- 9021637
TI  - Strategies for using chart audit.

PMID- 9021638
TI  - Nutritional assessments--when? Who?

PMID- 9021639
TI  - HIV education: a challenge to adult learning theory and practice.
AB  - While there are enormous bodies of literature that separately address adult
      learning theory and HIV disease education, there is a scarcity of literature that
      examines the way adult learning theory and education about HIV disease intersect.
      The author's focus is on successful, creative methods of combining these bodies
      of information in order to provide continuing education for health professionals.
      A review of the literature combined with the reported experience of AIDS
      Education and Training Centers (AETCs) from across the country identify useful
      strategies for successful HIV education.

PMID- 9021640
TI  - Professional nursing education's response to the HIV/AIDS pandemic.
AB  - Nurse educators have a responsibility to ensure that nursing students learn to
      respond to the healthcare needs of society even if those needs are evolving as
      the student's education is occurring. This paper examines the issues and
      challenges the HIV/AIDS epidemic presents to nurse educators. It then explores
      ways in which nursing education programs have responded to these challenges and
      develops a balanced discussion of these responses.

PMID- 9021641
TI  - Patient education for behavior change: help from the Transtheoretical and Harm
      Reduction models.
AB  - Promoting healthy behaviors at all levels of prevention is an important component
      of nursing care in the HIV epidemic. This paper explores two models that can be
      used to support behavior change efforts: the Transtheoretical Model, which
      describes stages in the change process, and the Harm Reduction Model, which
      offers an incremental approach to helping clients move toward safer and healthier
      habits. A review of the literature shows that these holistic and caring models
      can be combined effectively to assist clients who are dealing with HIV-related
      issues. The resulting theory-based approach can help nurses maintain consistency
      and direction in educational interventions for behavior change.

PMID- 9021643
TI  - Promoting cultural competence in HIV/AIDS care.
AB  - The importance of cultural competence in providing health care to a diverse
      patient population is well-recognized throughout the health professions, though
      there is as yet no widely accepted set of criteria for establishing and
      maintaining cultural competence. In HIV/AIDS, where behavioral factors figure so
      prominently in transmission, prevention, and treatment, cultural appropriateness
      is crucial to providing patient education and nursing care. This article suggests
      some specific cultural competence training strategies and offers a broad
      conceptual framework for teaching and learning about the issues involved in
      cultural competence, with specific illustrations relating to HIV/AIDS.

PMID- 9021644
TI  - Morphological study of neurons in the nerve plexus on heart base of rats and
      guinea pigs.
AB  - The paper describes the morphological pattern of neurons in the nerve plexus on
      the heart base of rats and guinea pigs. The nerve plexus, containing the
      investigated neurons, lies beneath the pulmonary arteries on the myocardium of
      the left atrium. This plexus is not covered by the epicardium. Therefore,
      contrary to the subepicardiac nerve plexus the investigated plexus was termed the
      nerve plexus of the cardiac hilum (NPCH). The morphology of neurons in the NPCH
      was revealed by ionophoretic injection of Lucifer Yellow via an intracellular
      microelectrode in vitro. A total of 139 neurons in 31 rats and 15 guinea pigs
      were labeled with dye and examined without chemical fixation with a fluorescent
      microscope. In the NPCH of both species, two types of neuron were revealed:
      unipolar and multipolar. The unipolar predominated (61.2% of the labeled nerve
      cells), whereas the multipolar were encountered less frequently (38.8% of the
      sampled neurons). Morphometrically, both types were similar and there was no
      significant difference in their length or width. The dyed neurons of both types
      were divided into separate groups according to indentations on the surface of
      their soma. Most of the unipolar nerve cells were encompassed into a group of
      "smooth' neurons because the surface of their soma was without noticeable
      prominences or grooves. The rest of the unipolar neurons were distinguished from
      the 'smooth' by various types of unevenness of the surface of their body, such as
      spine-like sprouts and grooves of different depth. The latter were attached to
      another group, the 'unsmooths', which made up 22.4% of all the labeled cells. The
      multipolar neurons were subdivided into two groups according to the number of
      long processes. The first group included neurons with a single long process,
      whereas the other group encompassed the nerve cells with two or more processes.
      The latter groups made up 31.6% and 7.2%, respectively, of the total number of
      labeled nerve cells. The obtained data have shown that the neurons in the NPCH of
      the rats and guinea pigs are morphologically different, and therefore it is
      proposed that the function of the neurons in the diverse groups may also be
      different.

PMID- 9021645
TI  - Clathrin light chain and synaptotagmin I in rat sympathetic neurons.
AB  - Clathrin light chain (clathrin LC) and synaptotagmin I in sympathetic neurons in
      rat superior cervical ganglia (SCG) were studied using immunofluorescence and
      confocal microscopy. The distributions of clathrin LC and synaptotagmin I were
      compared with that of tyrosine hydroxylase (TH) and neuropeptide Y (NPY) in
      double label experiments. The influence of preganglionic regulation on the
      expression of clathrin LC and synaptotagmin I in post-ganglionic adrenergic
      neurons was investigated after cutting the cervical sympathetic trunk. In SCGs
      and irides of control animals, the calthrin LC- and synaptotagmin-I-positive
      structures were present in a granular pattern in nerve fibers and varicose
      terminals. In principal neurons, the two proteins were present in a perinuclear
      network (the Golgi complex). After decentralization, the synaptotagmin-I- and
      clathrin LC-positive granules normally present in preganglionic nerve terminals
      outlining the neuronal somata were no longer observed on day 1, but reappeared,
      and were increased above control in number and intensity, in axon bundles in the
      ganglia, on day 3 and up to day 28 post-decentralization. In irides, the
      fluorescence intensity and density of clathrin LC- and synaptotagmin-I-positive
      nerve terminals in the dilator plate, were semi-quantified using the confocal
      microscopy software. It was found that both proteins increased shortly after
      decentralization. Immunoblot data confirmed the immunohistochemical/confocal
      microscopy observations. Fast axonal transport of clathrin LC- and synaptotagmin
      I in preganglionic sympathetic neurons was demonstrated in crush-operated
      cervical sympathetic trunk. Both proteins rapidly accumulated proximally as well
      as distally to the crush, demonstrating fast anterograde and retrograde axonal
      transport (recycling). Thus, clathrin LC and synaptotagmin I are normally present
      in pre- as well as post-ganglionic sympathetic neurons. The colocalization of
      clathrin LC with synaptotagmin I in the Golgi complex of the adrenergic neurons
      may imply that clathrin participates in the synthesis/sorting of the fast
      transported materials in these neurons. Possible explanations for the increase of
      the two proteins after decentralization are discussed.

PMID- 9021646
TI  - The central respiratory effects of acetylcholine vary with CSF pH.
AB  - Hydrogen ion concentration [H+] centrally is a major determinant of ventilation.
      Its action involves central cholinergic mechanisms. The point(s) where increased
      [H+] induces its changes in the cholinergic system is unclear. If H+ acts
      presynaptically by increasing endogenous ACh synthesis and release, its effect
      should be absent when ACh is supplied exogenously. If H+ acts postsynaptically by
      changing ACh degradation or ACh receptor sensitivity, its effect should persist
      in the presence of exogenous ACh. We perfused the brain ventricular system in
      spontaneously breathing anesthetized dogs with progressively higher
      concentrations of ACh (0-52.8 mM) in cerebrospinal fluid (CSF) at pH 7.4 and CSF
      pH 7.1. Increasing concentrations of ACh increased ventilation > 4-fold in a
      linear manner in the presence of non-acidic and acidic CSF. With acidic CSF the
      ACh ventilatory response line was shifted to a higher y-intercept, resulting in a
      higher ventilation at any [ACh]. These findings are consistent with the
      hypothesis that central acidosis augments ventilation by postsynaptic cholinergic
      events.

PMID- 9021647
TI  - Central vasopressin is required for the complete development of
      deoxycorticosterone-salt hypertension in rats with hereditary diabetes insipidus.
AB  - It has been shown that vasopressin receptors are upregulated in the brain and
      that the central vasopressin pathway is involved in the development of
      deoxycorticosterone acetate (DOCA)-salt hypertension. However, it is unclear
      whether central vasopressin, in itself, is essential for this type of
      hypertension. To clarify this issue, the effect of centrally administered
      vasopressin on the development of DOCA-salt hypertension was studied in
      homozygous Brattleboro rats which genetically lack vasopressin. In homozygous
      Brattleboro rats, treatment with intracerebroventricular infusion of vasopressin
      (1 ng/h) alone or DOCA-salt (weekly subcutaneous injection of 30 mg/kg
      deoxycorticosterone acetate and 0.3% NaCl to drink) alone had no effect on
      systolic blood pressure (SBP). On the other hand, hypertension was partially
      restored in homozygous Brattleboro rats treated with intracerebroventricular
      infusion of vasopressin and DOCA-salt (SBP: 175 +/- 4 mmHg), although the
      magnitude of elevation of SBP was one-third of that in Long Evans rats treated
      with DOCA-salt (278 +/- 15 mmHg). These hypertensive homozygous Brattleboro rats
      showed an increase in fluid intake and urinary sodium excretion, as observed in
      DOCA-salt hypertensive Long Evans rats. These results suggest that central
      vasopressin is required for the complete development of DOCA-salt hypertension
      and the mechanism is, in part, due to enhanced sodium intake through the additive
      effect of central vasopressin and DOCA-salt.

PMID- 9021648
TI  - Cardiovascular autonomic nervous system tests: determination of normative values
      and effect of confounding variables.
AB  - OBJECTIVE: To determine normative values for heart rate variation to deep
      breathing (VAR) and Valsalva ratio (VAL) as well as the effect of various
      confounding variables on these measures using data from a large group of normal
      subjects collected from multiple centers. RESEARCH DESIGN AND METHODS: VAR and
      VAL were measured on 611 normal subjects, age range 9-79, from 63 centers and was
      analyzed at a single Autonomic Nervous System Reading Center. Using simple and
      stepwise logistic regression the effect of age, gender, height, weight, mean
      arterial blood pressure (MAP) and body mass index (BMI), on VAR and VAL was
      evaluated. RESULTS: The 95% normative values range (values at 2.5 to 97.5
      percentile) for VAR (n = 580) was 12.8-103.5 (mean 49.7) and for VAL (n = 425)
      was 1.31-2.97 (mean 1.97). No gender effect was found for either VAR or VAL (p >
      0.05). VAR correlated inversely with both age and MAP, while VAL correlated
      inversely with both age and BMI. Since age is the principal confounding variable
      for both VAR and VAL, normative values are also presented stratified by age.
      CONCLUSION: Normative values for VAR and VAL based on a large population sample
      are presented. However, the values presented may not be valid in patients with
      morbid obesity or malignant hypertension. These data are applicable for either
      individual patients or for use in multicenter research trials.

PMID- 9021649
TI  - Autonomic nervous system response patterns specificity to basic emotions.
AB  - The aim of this study was to test the assumption that the autonomic nervous
      system responses to emotional stimuli are specific. A series of six slides was
      randomly presented to the subjects while six autonomic nervous system (ANS)
      parameters were recorded: skin conductance, skin potential, skin resistance, skin
      blood flow, skin temperature and instantaneous respiratory frequency. Each slide
      induced a basic emotion: happiness, surprise, anger, fear, sadness and disgust.
      Results have been first considered with reference to electrodermal responses
      (EDR) and secondly through thermo-vascular and respiratory variations. Classical
      as well as original indices were used to quantify autonomic responses. The six
      basic emotions were distinguished by Friedman variance analysis. Thus, ANS values
      corresponding to each emotion were compared two-by-two. EDR distinguished 13
      emotion-pairs out of 15. 10 emotion-pairs were separated by skin resistance as
      well as skin conductance ohmic perturbation duration indices whereas conductance
      amplitude was only capable of distinguishing 7 emotion-pairs. Skin potential
      responses distinguished surprise and fear from sadness, and fear from disgust,
      according to their elementary pattern analysis in form and sign. Two-by-two
      comparisons of skin temperature, skin blood flow (estimated by the new non
      oscillary duration index) and instantaneous respiratory frequency, enabled the
      distinction of 14 emotion-pairs out of 15. 9 emotion-pairs were distinguished by
      the non-oscillatory duration index values. Skin temperature was demonstrated to
      be different i.e. positive versus negative in response to anger and fear. The
      instantaneous respiratory frequency perturbation duration index was the only one
      capable of separating sadness from disgust. From the six ANS parameters study,
      different autonomic patterns were identified, each characterizing one of the six
      basic emotion used as inducing signals. No index alone, nor group of parameters
      (EDR and thermovascular for instance) were capable of distinguishing each emotion
      from another. However, electrodermal, thermo-vascular and respiratory responses
      taken as a whole, redundantly separated each emotion thus demonstrating the
      specificity of autonomic patterns.

PMID- 9021650
TI  - Involvement of 5-hydroxytryptamine (5-HT)3 receptor mechanisms in regulation of
      basal pancreatic secretion in conscious rats.
AB  - The effects of 5-hydroxytryptamine (5-HT)3 receptor antagonists (azasetron and
      granisetron) on basal pancreatic exocrine secretion were examined in conscious
      rats. Rats were prepared with cannulae draining bile and pancreatic juice
      separately. Intravenous injection of azasetron significantly increased pancreatic
      fluid and protein outputs in a dose-dependent manner. These increases were
      completely abolished by treatment with atropine, but not affected by bilateral
      truncal vagotomy. Intravenous injection of granisetron also increased pancreatic
      secretion, significantly. Intragastric injection of azasetron increased
      pancreatic secretion, although a double dose was required to elicit the
      stimulatory effect compared with intravenous injection. It is concluded that 5
      HT3 receptor activity is involved in regulation of basal pancreatic secretion in
      conscious rats.

PMID- 9021651
TI  - Improved orthostatic tolerance in familial amyloidotic polyneuropathy with
      unnatural noradrenaline precursor L-threo-3,4-dihydroxyphenylserine.
AB  - Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous
      system, is a common complication of type I familial amyloidotic polyneuropathy
      (FAP). We investigated whether oral treatment with L-threo-3,4
      dihydroxyphenylserine (L-threo-Dops), a noradrenaline precursor, might be of
      therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years,
      who, because of severe orthostatic hypotension, were bedridden or constrained to
      a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and
      tilting time, defined as the interval (s) between the beginning of a 60 degrees
      head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred
      vision or near syncope) were determined before and at repeated intervals during
      oral treatment with L-threo-Dops, 100 mg bid, for 6 months. Before treatment
      supine mean BP was 80 (76-85) mmHg (mean and 95% CI), supine plasma noradrenaline
      was low, 59 (41-77) pg/ml and tilting time ranged from 38 to 118 s. In response
      to tilt, mean BP immediately fell by 36 (31-41) mmHg, whereas plasma
      noradrenaline increased by only 11 (0-21) pg/ml (p = 0.05). After 3 to 5 days of
      treatment with L-threo-Dops all patients experienced marked improvement of their
      orthostatic tolerance as reflected by their ability to walk freely around. This
      effect sustained throughout the six months of treatment. Plasma noradrenaline
      increased moderately by 37 (11-63) pg/ml (p = 0.02) and supine mean BP increased
      by 8.6 (5.8-12.4) mmHg (p < 0.001) during chronic treatment. Supine or nocturnal
      hypertension did not develop, the fall in mean BP in response to tilt diminished
      by 12.5 (6.5-17.3) mmHg (p < 0.001) and tilting time became longer than 600 s in
      all patients. Because of its efficacy, its sustained duration of action and the
      lack of side effects, L-threo-Dops is advocated to improve orthostatic tolerance
      in patients with autonomic insufficiency due to FAP.

PMID- 9021652
TI  - Interleukin-1 increases activity of the gastric vagal afferent nerve partly via
      stimulation of type A CCK receptor in anesthetized rats.
AB  - The response of mass activity of the gastric vagal afferent nerve to intravenous
      administration of interleukin-1 beta (IL-1 beta) and the involvement of
      cholecystokinin (CCK) in the response were investigated in pentobarbital
      anesthetized rats. Intravenous administration of 2 micrograms.kg-1 of IL-1 beta
      caused an increase in the afferent activity, which reached 150% of control
      activity by 30 min after administration and persisted for more than 80 min. The
      increase in the nerve activity was significantly reduced in animals pretreated
      with a type A CCK receptor antagonist. IL-1 beta also significantly increased the
      CCK concentration in systemic blood. Furthermore, it was confirmed that
      intravenous administration of CCK produced an increase in the nerve activity via
      the type A CCK receptor. These findings suggest that systemically applied IL-1
      beta increases CCK concentration in systemic blood secreted from mucosal
      endocrine cells of the small intestine, and that in turn CCK in the gastric blood
      flow augments or partly participates in the IL-1 beta-induced excitation of the
      gastric vagal afferent nerve via stimulation of the type A CCK receptor in the
      stomach. A possible involvement of IL-1-related excitation of the gastric vagal
      afferent nerve in IL-1-induced anorexia is discussed.

PMID- 9021653
TI  - A new method of assessing cardiac autonomic function and its comparison with
      spectral analysis and coefficient of variation of R-R interval.
AB  - A new non-linear method of assessing cardiac autonomic function was examined in a
      pharmacological experiment in ten healthy volunteers. The R-R interval data
      obtained under a control condition and in autonomic blockade by atropine and by
      propranolol were analyzed by each of the new methods employing Lorenz plot,
      spectral analysis and the coefficient of variation. With our method we derived
      two measures, the cardiac vagal index and the cardiac sympathetic index, which
      indicate vagal and sympathetic function separately. These two indices were found
      to be more reliable than those obtained by the other two methods. We anticipate
      that the non-invasive assessment of short-term cardiac autonomic function will
      come to be performed more reliably and conveniently by this method.

PMID- 9021654
TI  - Variation in mRNA expression of alpha-adrenergic, neurokinin and muscarinic
      receptors amongst four arteries of the rat.
AB  - Different mechanisms mediate constriction and dilation in different vascular
      beds. We have used reverse transcription-polymerase chain reaction to investigate
      whether specific patterns of receptor gene expression may underlie these variable
      responses. Total RNA, from the basilar, pulmonary, mesenteric and tail arteries
      of anaesthetised adult Wistar rats, was reverse transcribed and amplified using
      primers specific for the molecular subtypes of the alpha 1(A, B, D)- and alpha
      2(A, B, C)-adrenergic, neurokinin (NK1-NK3) and muscarinic (m1-m5), receptors.
      Results showed that the pattern of gene expression was variable with no two
      arteries having the same receptor profile. Messenger RNA for the alpha 1A, alpha
      1B, alpha 2B, NK1, NK3, m3 and m5 receptor subtypes were detected in all vessels
      studied while the remaining subtypes showed a variable expression amongst the
      arteries. This is the first description of mRNA for the m5 muscarinic receptor in
      peripheral tissue. The NK3 receptor was the major neurokinin receptor expressed
      in all vessels except the pulmonary artery, in which the NK1 receptor was also
      strongly expressed. We conclude that each artery expressed a specific receptor
      array which may permit some unique neural and hormonal controls.

PMID- 9021655
TI  - Distension-evoked ascending and descending reflexes in the isolated guinea-pig
      stomach.
AB  - Distension-evoked gastric reflexes were studied by intracellular recording from
      circular muscle cells in the gastric fundus, corpus and antrum in the isolated
      guinea-pig stomach. Localised electrical stimulation, 2 mm circumferential to the
      recording electrode, evoked inhibitory junctions potentials in all three gastric
      regions, sometimes followed by depolarisations in the antrum. In the mid corpus,
      the inhibitory responses were substantially reduced by Nw-nitro-L-arginine (100
      microM), unmasking excitatory junction potentials. Residual hyperpolarisations
      were blocked by apamin (0.5 microM) which also enhanced the amplitude of
      excitatory junction potentials. These excitatory junction potentials were
      abolished by hyoscine (1 microM). Thus transmission from inhibitory motor neurons
      is mediated by both nitric oxide and an apamin-sensitive mechanism. Transmission
      from excitatory motor neurons to the circular muscle is mediated by acetylcholine
      via muscarinic receptors. Balloon distension of 10 s duration of the fundus or
      antrum elicited inhibitory junction potentials in circular muscle cells of the
      mid corpus. These inhibitory junction potentials were blocked by tetrodotoxin
      (0.6 microM) and were greatly reduced by Nw-nitro-L-arginine (100 microM). The
      residual hyperpolarisations were blocked by apamin (0.5 microM). This indicates
      the presence of ascending and descending inhibitory reflex pathways in the
      stomach. In 3 out of 7 experiments, following blockade of inhibitory
      transmission, small nerve-mediated excitatory junction potentials were evoked by
      antral distension indicating the presence of an additional ascending excitatory
      reflex pathway. Distension of the corpus elicited prominent inhibitory junction
      potentials, sometimes followed by large depolarisations, in circular muscle cells
      in the fundus, but not in the antrum. This suggests that there is also an
      ascending inhibitory reflex pathway from the corpus to the fundus but no
      distension-sensitive descending reflex pathway from the corpus to the antrum.
      These results demonstrate that within the stomach there are reflex pathways which
      can be activated by localised distension and project at some distance orally and
      aborally within the gastric wall. It is likely that the inhibitory reflex
      pathways are involved in gastric adaptive relaxation which occurs when the
      intact, isolated stomach is distended. The excitatory reflex pathways from the
      antrum to the corpus are likely to be involved in the intrinsic excitatory reflex
      responses observed in the isolated intact stomach to distension and thus be
      involved in the mixing and emptying of gastric contents.

PMID- 9021656
TI  - Activation of P2x-purinoceptors in the nucleus tractus solitarius elicits
      differential inhibition of lumbar and renal sympathetic nerve activity.
AB  - Activation of P2x-purinoceptors in the nucleus tractus solitarius (NTS) via
      microinjection of alpha,beta-methylene ATP (alpha,beta-MeATP) elicits large dose
      dependent decreases in mean arterial pressure (MAP) and heart rate (HR) and
      preferential dilation of the iliac vascular bed in comparison to renal and
      mesenteric vascular beds. We investigated whether sympathoinhibition contributes
      to the depressor responses and whether differential changes in regional
      sympathetic output occur. In 43 chloralose/urethane anesthetized male Sprague
      Dawley rats, MAP, HR, renal (RSNA) and lumbar sympathetic nerve activity (LSNA)
      were recorded. Data were analyzed as both the maximum decrease and the integral
      of the decrease over the duration of the depressor response. Microinjection of
      alpha,beta-MeATP (25 and 100 pmol in 50 nl volume) into the subpostremal NTS
      caused significant and dose-dependent decreases in MAP, HR, RSNA and LSNA.
      However, the changes in RSNA were significantly greater than those observed in
      LSNA for both doses and both methods of analysis of data (maximum responses in
      delta %: 84 +/- 3 vs 62 +/- 4, and 93 +/- 3 vs 74 +/- 4 for low and high dose of
      alpha,beta-MeATP, respectively; integral responses in delta % x min: 32 +/- 4 vs
      18 +/- 3 and 179 +/- 7 vs 134 +/- 14 for low and high dose of alpha,beta-MeATP,
      respectively). Blockade of P2-purinoceptors in the NTS by the specific P2
      receptor antagonist suramin abolished responses to 100 pmol alpha,beta-MeATP and
      microinjections of vehicle did not alter neural nor hemodynamic parameters. We
      conclude that activation of P2x-purinoceptors in the NTS inhibits sympathetic
      nerve activity and evokes differential regional sympathetic responses. However,
      differential sympathoinhibition does not explain differential vascular responses
      to the activation of P2x-purinoceptors in the NTS.

PMID- 9021657
TI  - [Effect of fenitrothion on experimental allergic conjunctivitis].
AB  - The effect of fenitrothion on experimental allergic conjunctivitis was studied
      using guinea pigs. Guinea pigs were passively sensitized with anti-sera against
      ovalbumin (OVA) or Japanese cedar pollen. Eight days after the sensitization, 6 x
      10(-5) mg/kg to 6 mg/kg of fenitrothion were administered subcutaneously. Two
      days after the injection, OVA or Japanese cedar pollen was given in the
      conjunctival sac and the allergic conjunctivitis was examined. OVA or Japanese
      cedar pollen induced the allergic conjunctivitis, depending on the challenge
      dosage (OVA). However, no adverse effect of fenitrothion was observed on allergic
      conjunctivitis challenged with OVA or Japanese cedar pollen. An anti-allergic
      agent, ketotifen, suppressed the allergic intensity. These results indicate that
      fenitrothion has no adverse effect on the experimental allergic conjunctivitis.

PMID- 9021658
TI  - [Oral single-dose toxicity study of a new antineoplastic agent S-1, and its
      components, CDHP, and Oxo].
AB  - S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative
      containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of
      1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim
      of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over
      that produced by FT alone and reducing its dose-limiting gastrointestinal
      toxicity. As a part of the S-1 toxicity study, the single-dose toxicity of S-1 as
      well as that of its components, CDHP and Oxo, was investigated in mice, rats, and
      dogs. The following results were obtained. 1. In mice and rats, excretion of
      diarrheal stools, salivation, and alopecia were observed after S-1
      administration. In severe cases, the animals subsequently showed emaciation due
      to weight loss or suppressed weight gain, decreased spontaneous motor activity,
      an anemic appearance, bradypnea, prone position, and death. In the CDHP and Oxo
      treatment groups of rats, the only toxic signs were soft or diarrheal stools on
      the dosing day. 2. In dogs, vomiting and excretion of diarrheal, mucous, or soft
      stools was observed after S-1 administration. In the CDHP and Oxo treatment
      groups, excretion of soft and diarrheal stools and vomiting were observed
      relatively frequently from the dosing day until day 1. 3. In the pathological
      examination of the animals given S-1, mice and rats showed pulmonary
      congestion/edema, dark red discoloration of the mesenteric lymph nodes, atrophy
      of lymphatic tissues such as the thymus and lymph nodes, decreases of lymphocytes
      in the splenic white pulp and mesenteric lymph nodes, a decrease in bone marrow
      cells, congestion of the glandular stomach, and aggregates of bacteria in the
      lung, liver, or spleen. In dogs, abnormal changes were observed mainly in the
      lymphatic organs such as the thymus and lymph nodes. 4. The LD50 values of S-1 in
      terms of the amount FT they contained were estimated to be 549 mg/kg for
      mice(male), 441-551 mg/kg for rats (both sexes) and about 53 mg/kg for dogs
      (male). The LD50 values of CDHP and Oxo were 2000 mg/kg or higher for both rats
      (both sexes) and dogs (male). 5. Hematopoietic and lymphatic impairments,
      immunosuppression associated with respiratory were considered to be the cause of
      death from S-1. The toxicity of S-1 reflects the toxicity of 5-FU and was not
      found the different toxicity by the addition of CDHP and Oxo.

PMID- 9021659
TI  - [A 13-week oral repeated dose toxicity study of a new antineoplastic agent S-1 in
      rats].
AB  - S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative
      containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of
      1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim
      of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over
      that produced by FT alone and reducing its dose-limiting gastrointestinal
      toxicity. As a part of the S-1 toxicity study, a 13-week oral repeated dose
      toxicity study and a recovery study using male and female rats was conducted.
      Doses of S-1 were adjusted to deliver 1.5, 5, and 15 mg/kg/day as doses of FT,
      and FT was given at 15 mg/kg/day. The following results were obtained. 1. In
      clinical observation, edema of the limbs and face or swelling of the auricle of
      the ear and an anemic appearance were observed in both sexes in the 15 mg/kg/day
      group as dose of FT. Subsequently, males in this group developed severe anemia,
      decreased spontaneous motor activity, emaciation, and subnormal skin temperature,
      and many males died. In the survivors, keratosis of the palm, sole, or tail was
      observed, with necrosis and loss of the tail tip in the severe cases. 2. Body
      weight gain was suppressed from about week 2 of treatment in both sexes in the 15
      mg/kg/day group as dose of FT, and there was almost no weight gain after week 4
      5. Food consumption was consistently less than the control value for males in the
      15 mg/kg/day group as dose of FT throughout the treatment period. 3. No marked
      changes were observed in water intake and on opthalmologic examination. 4. In the
      fecal test for occult blood, a positive tendency was observed in both sexes in
      the 15 mg/kg/day group as dose of FT. 5. Urinalysis disclosed a slight increase
      in protein and decrease in sodium, potassium, and chloride in males, and an
      increase in protein in females in the 15 mg/kg/day group as dose of FT. 6.
      Hematologically, both sexes in the 15 mg/kg/day group as dose of FT showed
      decreases in red blood cell count, hemoglobin, and hematocrit, and increases in
      platelet count and fibrinogen, with a slight decrease in white blood cell count
      in males. 7. In the blood biochemical test, abnormal findings included increases
      in total cholesterol and free cholesterol, and decreases in non-esterified fatty
      acid and albumin in both sexes in the 15 mg/kg/day group as dose of FT. 8. In
      organ weight measurement, abnormal changes included a decrease in thymus weight
      in both sexes in the 5 mg/kg/day or higher dosage groups and a decrease in the
      testis weight in males and an increase in the liver weight in females in the 15
      mg/kg/day group as dose of FT. 9. Histopathologically, both sexes in the 15
      mg/kg/day group as dose of FT showed a decrease in the red pulp of the bone
      marrow, atrophy of the thymus, white pulp of the spleen, and testes. degeneration
      of the renal tubules, and ulcerative changes of the skin or oral mucosa. 10. The
      findings were unremarkable in the FT group. 11. During the recovery study, all
      the toxic effects tended to reverse. 12. The NOAEL of S-1 was estimated to be 1.5
      mg/kg/day as dose of FT for both sexes.

PMID- 9021660
TI  - [An oral repeated dose toxicity study of a new antineoplastic agent S-1 in dogs.
      I. A 13-week repeated dose toxicity study. II. An ophthalmologic toxicity
      recovery study].
AB  - S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative
      containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of
      1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim
      of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over
      that producted by FT alone and reducing its dose-limiting gastrointestinal
      toxicity. As a part of the S-1 toxicity study, a 13-week repeated dose toxicity
      study and a recovery study of opthalmologic effects were conducted in dogs. The
      following results were obtained. All S-1 doses are expressed in terms of their FT
      content. 1. Concerning the general condition, dark brown pigment was deposited on
      the sclera of the eye in all S-1 treated groups starting at the second week of
      treatment, and clouding of the cornea was noted in the 3 mg/kg/day group starting
      after 3-4 weeks of treatment. In the 3 and 6 mg/kg/day groups, general signs such
      as salivation, reduction in spontaneous movements, and sedation appeared, and 1
      male and 2 females of the 3 mg/kg/day group died or were moribund 4-5 weeks after
      treatment began. All animals of the 6 mg/kg/day died or were sacrificed within 2
      weeks of the start of the study. 2. Food consumption and body weight were reduced
      in the groups administered 1 mg/kg/day or more S-1. 3. No apparent drug-induced
      changes were observed on electrocardiography, urinalysis, fecal occult blood
      test, hematological examination, liver and kidney function tests, or ocular
      mucosa infection tests. 4. Blood biochemical examinations showed decreases in
      creatinine and chloride levels in males, an increase in LDH activity, and
      decreases in the albumin level and A/G ratio in females of the 3 mg/kg/day group.
      5. Organ weighing showed that the relative weight of the kidney was increased in
      males and females of the 3 mg/kg/day group. 6. Histopathological examination
      revealed melanin deposition in the conjunctiva or cornea and atrophy
      inflammation, neutrophil infiltration, and neovascularization in the corneal
      epithelium. Atrophy of lymphatic tissues, such as the thymus, spleen and various
      lymph nodes, and changes in the reproductive system such as aspermatogenesis and
      uterine atrophy, which are commonly observed side effects of anticancer drugs,
      were also noted. 7. In the group administered FT, vacuolation of the cerebral
      fornix and commissura anterior was observed in 1 animal, but no changes were
      observed in other examinations. 8. The toxic effects of S-1 appeared primarily in
      the eyes, lymphatic tissues, and reproductive organs, and deaths were ascribed to
      weakening due to exacerbation of the general effects accompanied by disorders of
      immunological function. The NOAEL of S-1 in this study was estimated to be the
      dose that delivered less than 0.5 mg/kg/day in both males and females. 9. Changes
      in the eye observed after S-1 administration are such as pigmentation of the
      sclera and white turbidity of the cornea. Though it may be produced vision
      decreased, these changes are considered to be unaccompanied by functional
      disorders and to be reversible.

PMID- 9021661
TI  - [A 26-week oral repeated dose toxicity study of a new antineoplastic agent S-1 in
      rats].
AB  - S-1 was administered to male and female rats by gavage for 26 weeks at 0, 1, 5,
      and 10 mg/kg/day followed by 5-week recovery period for the control, 5, and 10
      mg/kg/day groups. Treatment at 5 or 10 mg/kg/day in both sexes produced keratosis
      of the tail, palm or sole. Weight gain and average food consumption were lowered
      by the treatment. Urine showed increases in protein and epithelial or white blood
      cells and a decrease in specific gravity. The blood showed decreases in red blood
      cell count, hemoglobin, and hematocrit as well as increases in MCH, platelet
      count, fibrinogen, and MCV. A/G ratio, albumin, and chloride were decreased while
      total cholesterol, free cholesterol, triglycerides, and phospholipids were
      increased. Histopathologically, treatment-related changes at 5 and 10 mg/kg/day
      were observed mainly in the lymphoid tissues and kidneys. Those changes included
      atrophy in the lymphoid tissues and chronic nephropathy-like changes in the
      kidneys. Other changes in the 10 mg/ kg/day group, included acanthosis and/or
      inflammation in the epidermis of the tail, sole, or palm, degeneration and
      disarrangement of ameloblasts, and atrophy of the testes. In a recovery study,
      although some changes in the sole, palm, or tail, and the kidneys remained, they
      were less extensive than they had been at the end of the treatment period. Based
      upon these observations, the non-toxic dose level was estimated to be 1 mg/kg/day
      (2.3 mg/kg/day, as the summed doses of tegafur, CDHP, and Oxo) in both sexes.

PMID- 9021662
TI  - [A 52-week oral toxicity study of a new antineoplastic agent S-1 in dogs].
AB  - 52-week oral repeated-dose S-1 toxicity studies were conducted. Male and female
      dogs were orally treated with 0, 0.1, 0.5 or 2.5 mg/kg/day for 52 weeks and
      permitted to recover for 13 weeks. Furthermore, to estimate the no-toxic dose,
      male and female dogs were given S-1 orally for 52 weeks at doses of 0, 0.004 and
      0.02 mg/kg/day. The 2.5 mg/kg/day regimen produced one dead or moribund dog of
      each sex; black-brown patch (melanin deposition) and inflammatory changes in the
      eyes and skin; decreased in body weight gains; increases in MCV, MCH, monocyte
      ratio, and serum protein and uric acid; decreases in lymphocyte ratio and
      erythrocyte count, hematocrit, hemoglobin, albumin, A/G ratio, cholesterol
      (esterified, total and free), phospholipids, triglycerides, cholinesterase
      activity and creatinine; increases in relative liver and adrenal weights.
      Histopathological examinations revealed melanin deposits in superficial lymph
      nodes, increases in macrophage and plasma cell accumulation, and corneal atrophy
      accompanied by melanin deposits and capillary proliferation. A slight black-brown
      patch (melanin deposition) in the conjunctiva and skin was observed in the 0.1
      and 0.5 mg/kg/day groups. No drug-related changes were observed in groups that
      received 0.02 and 0.004 mg/kg/day. All changes observed during the treatment
      period disappeared during recovery except for melanin deposits in the conjunctiva
      and superficial lymph nodes, corneal opacity, and a few hematological and blood
      chemistry parameters. In conclusion, the no-toxic dose in these 52-week studies
      was estimated to be 0.02 mg/kg/day.

PMID- 9021663
TI  - [Reproductive and developmental toxicity study of a new antineoplastic agent, S-1
      (I)--Fertility study in rats by oral administration].
AB  - S-1 is a newly developed antineoplastic agent consisting of the mixture of
      tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo)
      in a molar ratio of 1:0.4:1. As part of a reproductive and developmental toxicity
      study of S-1, a fertility study was carried out in Sprague-Dawley rats. Twenty
      four male rats were administered S-1 orally starting at 64 days before mating and
      24 female rats were administered S-1 orally from 15 days before mating to day 7
      of pregnancy at doses of 0, 1, 4, or 7 mg/kg/day (as a dose of FT) in order to
      investigate the effect of S-1 on the reproductive ability and development of
      embryos and fetuses. There were no dose-related changes in clinical signs. Body
      weight gains and food consumption were decreased and were associated with the
      decreased weights of thymus, testis and epididymis in male rats receiving S-1 at
      the 7 mg/kg/day group. In females, the only organ affected was the kidney at 7
      mg/kg/day. There were no dose-related changes in copulation, fertility, pre
      implantation loss and implantation. Decreases in live fetal body weight and
      retardation of fetal ossification were observed in the 7 mg/kg/day group. There
      were no dose-related changes in post-implantation loss, and no fetal
      malformations were observed. The results suggest that the non-observed effects
      dose level of S-1 for general toxicity in male and female rats in 4 mg/kg/day,
      for reproductive toxicity in adults is more than 7 mg/kg/day, and for
      developmental toxicity in utero is 4 mg/kg/day.

PMID- 9021665
TI  - [Reproductive and developmental toxicity study of a new antineoplastic agent, S-1
      (III)--Teratological study in rabbits by oral administration].
AB  - S-1 is a newly developed antineoplastic agent consisting of the mixture of
      tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo)
      in a molar ratio of 1:0.4:1. As part of a reproductive and developmental toxicity
      study of S-1, a teratogenicity study was carried out in rabbits administered
      daily oral doses of S-1 0, 0.5, 1, or 1.5 mg/kg/day (as a dose of FT). S-1 was
      administered from day 6 to day 18 of pregnancy. Two additional studies were
      conducted in order to evaluate the effect on embryos or fetuses at higher S-1
      dosage. One study (additional study I) tested during organogenesis dividing it
      into 3 periods (Day 6-10, Day 10-14, and Day 14-18) at doses of 2, 4 or 6
      mg/kg/day. Another study (additional study II) tested during organogenesis
      dividing it into 4 periods (Day 8 x 9, Day 10 x 11, Day 12 x 13, and Day 14 x 15)
      at doses of 3 or 6 mg/kg/day due to many embryo deaths at high dose level in the
      additional study I. The results were as follows. 1. Teratogenicity study One dam
      died on day 16 of pregnancy and there was a weak teratogenic potential in the 1.5
      mg/kg/day group. There were no remarkable other changes in dams and fetuses. The
      non-observed effects dose level of S-1 for general toxicity in dams was 1
      mg/kg/day, for pregnancy in dams was 1.5 mg/kg/day, and for development of
      fetuses was 1 mg/kg/day under the conditions of this study. 2. Additional study I
      Abortion was observed at 6 mg/kg/day in the day 14-18 administration group.
      General toxicity in dams were observed in all administration groups. Fetal
      lethality was observed at 4 mg/kg/day or more in the day 6-10 and day 10-14
      groups, and at 6 mg/kg/day in the day 14-18 administration group. Inhibition of
      fetal growth was observed at 2 mg/kg/day in the day 10-14 group and at 2
      mg/kg/day or more in the day 14-18 administration group. There was a week
      teratogenic potential at 2 mg/kg/day or more in the day 10-14 groups and at 4
      mg/kg/day in the day 14-18 administration group. 3. Additional study II Abortion
      was observed at 6 mg/kg/day in the day 8-9, day 10-11, and day 12-13
      administration groups. General toxicity in dams were observed in all
      administration groups. Fetal lethality was observed at 3 mg/kg/day in the day 8-9
      group and at 6 mg/kg/day in all administration groups. Inhibition of fetal growth
      and teratogenic potential were clearly observed at 3 mg/kg/day in the day 8-9 and
      day 10-11 groups, and at 6 mg/kg/day in the day 12-13 and day 14-15
      administration groups. 4. In conclusion, when S-1 was administered at a low dose
      (< = or 1.5 mg/kg/day) during organogenesis effects were not detected clearly.
      When higher doses were administered (2-6 mg/kg/day), fetal lethality, inhibition
      of fetal growth, and teratogenicity were observed.

PMID- 9021664
TI  - [Reproductive and developmental toxicity study of a new antineoplastic agent, S-1
      (II)--Teratological study in rats by oral administration].
AB  - S-1 is a newly developed antineoplastic agent consisting of the mixture of
      tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo)
      in a molar ratio of 1:0.4:1. The teratogenic potential of S-1 was studied in rats
      given S-1 at the daily oral doses of 0, 1, 3, 5 and 7 mg/kg/day (as a dose of
      FT). S-1 was given from day 7 to day 17 of pregnancy. The study included
      postnatal evaluation of the growth, development, and reproductive performance of
      the F1 generation. In rats receiving 7 mg/kg of S-1, maternal body weight gain
      and food consumptions were reduced, stillbirths increased, livebirths decreased
      slightly and F1 viability decreased. Fetal body weights decreased significantly
      in rats receiving 5 mg/kg or more of S-1. External and skeletal anomalies did not
      increase, but hydrocephaly increased slightly and total number of visceral
      anomalies increased significantly in the fetuses of rats receiving 7 mg/kg of S
      1. Hydrocephaly was observed also in F1 offspring from the rats receiving 7 mg/kg
      of S-1 during lactation period. Body weight gains of F1 offspring from the rats
      receiving 7 mg/kg of S-1 during lactation period was reduced. Functional
      development, emotional tests, learning tests, reproductive performance of the F1
      generation and development of the F2 generation were not effected by the S-1
      administration. In conclusion, under the condition of this study, the non
      observed effect dose levels (NOELs) of S-1 for general toxicity for dams was 5
      mg/kg/day, however, NOELs of S-1 was determined to be 7 mg/kg/day or more for
      reproductive ability. The NOELs of S-1 for the offspring was established to be 3
      mg/kg/day.

PMID- 9021666
TI  - [Reproductive and developmental toxicity study of a new antineoplastic agent, S-1
      (IV)--Perinatal and postnatal study in rats by oral administration].
AB  - S-1 is a newly developed antineoplastic agent consisting in a molar ratio of
      1:0.4:1 mixture of tegafur (FT), 5-chloro-2, 4, dihydroxypyridine (CDHP) and
      potassium oxonate (Oxo) was administered orally to SD rats at doses of 0, 1, 4
      and 7 mg/kg/day (as a dose of FT) during the perinatal and postnatal periods to
      examine its effect on dams and postnatal growth of the offspring. A group as the
      control was treated only with medium (0.5% hydroxypropyl methylcellulose)
      solution. The administration of 7 mg/kg/day to dams caused suppression in body
      weight gains and in food consumption during the treatment period. No adverse
      effects of S-1 on the length of gestation, gestation index, delivery and nursing
      ability were found. The administration of 4 and 7 mg/kg/day caused suppression in
      body weight gains in offspring of both sexes. Significant decrease in kidney
      weights were observed in females of the 4 mg/kg/day group and in both sexes of
      the 7 mg/kg/day group. No adverse effects of S-1 were found in number of live
      offspring at birth, sex ratio of live offspring, number of dead offspring at
      birth, birth index, viability index, weaning index, incidence of external
      anomalies, general conditions, postnatal development, reflex responses, motor
      coordination, emotional behavior, learning ability, skeletons, necropsy findings
      or reproductive functions. No adverse effects of S-1 on F2 offspring were found
      in any treatment groups. Under the conditions of the present study, the non
      observed effect dose levels of S-1 was 4 mg/kg/day for general toxicology of
      dams, 7 mg/kg/day for reproductive ability of dams, 1 mg/kg/day for postnatal
      growth in F1 offspring and 7 mg/kg/day for postnatal growth in F2 offspring.

PMID- 9021667
TI  - [Antigenicity tests of a new antineoplastic agent S-1].
AB  - The antigenicity was tested of a new antineoplastic agent S-1 (a combination of
      tegafur (FT), CDHP and potassium oxonate (Oxo)) in mice and guinea pigs. 1. Male
      BALB/c or C3H/He mice were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP
      (or Oxo) and human serum albumin (HSA). S-1 was administered by oral gavage, and
      the other compounds were administered intraperitoneally with adjuvant (alum). In
      the heterologous passive cutaneous anaphylaxis (PCA) test, using Sprague-Dawley
      rats as recipients, no IgE antibodies against S-1, CDHP, or Oxo were detected to
      any serum obtained from the sensitized mice, and no eliciting antigenicities were
      seen for CDHP or Oxo. 2. Male Hartley guinea pigs were sensitized with S-1, CDHP,
      Oxo, and conjugates of CDHP (or Oxo) and HSA. S-1 was administered by oral
      gavage, and the other compounds were administered subcutaneously with Freund's
      complete adjuvant (FCA). The homologous PCA test, active systemic anaphylaxis
      test, and passive hemagglutination test showed no production of antibodies
      against S-1, CDHP, or Oxo in any sensitized guinea pig, and no eliciting
      antigenicities for CDHP or Oxo. 3. Female Hartley guinea pigs were sensitized
      with S-1 subcutaneously with FCA. The active cutaneous anaphylaxis test revealed
      that S-1 did not induce cell-mediated delayed type hypersensitivity. 4. These
      results indicated that S-1, Oxo, and CDHP were not antigenic in mice and guinea
      pigs.

PMID- 9021668
TI  - [Mutagenicity study of a new antineoplastic agent S-1, and its components, CDHP,
      and Oxo].
AB  - S-1 is a new antineoplastic agent of a fluorinated pyrimidine derivative
      containing tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium
      oxonate (Oxo) in a molar ratio of 1:0.4:1 with the aim of prolonging the
      effective plasma concentration of 5-fluorouracil (5-FU) and reducing its dose
      limiting gastrointestinal toxicity. As a part of the safety evaluation of S-1,
      reverse mutation tests using bacteria and chromosomal aberration tests using
      cultured cells, CHL/IU, were conducted to test the in vitro mutagenicity of S-1,
      CDHP and Oxo. All S-1 doses are expressed as the content of FT. 1. The reverse
      mutation tests were carried out on S-1 at 1.02-520 micrograms/plate, on CDHP at
      39.1-5000 micrograms/plate, and on Oxo at 78.1-5000 micrograms/plate using
      Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia
      coli WP2uvrA. None of the test compounds induced a significant increase over
      solvent controls in the number of mutant colonies in any tester strains in either
      system, with or without mammalian metabolic activation (S9 Mix). 2. For the in
      vitro chromosomal aberration tests, Chinese hamster lung cells (CHL/IU), were
      treated with S-1 at 27.5-220 micrograms/ml for 24 hr or at 6.88-27.5
      micrograms/ml for 48 hr without S9 Mix, and at 110-880 micrograms/ml with S9 Mix,
      with CDHP at 365-1460 micrograms/ml (10 mM), and with Oxo at 122-1950
      micrograms/ml (10 mM), with and without S9 Mix. S-1 with and without S9 Mix, and
      Oxo only for 48 h treatment without S9 Mix, induced chromosomal aberrations,
      while CDHP did not. 3. The present study indicates that S-1 was nonmutagenic in
      bacteria, but clastogenic in vitro. CDHP had no in vitro mutagenic or clastogenic
      activity. Oxo was positive in the in vitro chromosomal aberration test, but
      negative in the reverse mutation test.

PMID- 9021670
TI  - Relative bioavailability of zinc methionine and two inorganic zinc sources fed to
      cattle.
AB  - A 12-week experiment was conducted to compare supplemental ZnMet, ZnSO4, and ZnO
      on Zn, Cu and metallothionein (MT) concentrations in various fluids and tissues
      of 32 yearling cattle. Supplemental Zn (360 mg per day) was fed for four weeks,
      withdrawn for four weeks, and then resumed for another four weeks. Mineral (Zn
      and Cu) concentrations were determined in serum, liver, pancreas, kidney, bone,
      bone marrow (metacarpus), hair, hoof and neck muscle (sterno mandibularis), and
      Zn only in erythrocytes, skin and cornea. Metallothionein levels were determined
      in liver, pancreas and kidney. There were no treatment differences (p > 0.05) in
      serum or erythrocyte Zn content for all days of collection. Serum Cu
      concentrations tended to decrease with all treatments. There were no treatment
      differences (p > 0.05) in Zn and Cu tissue concentrations and liver, kidney and
      pancreas MT concentrations. Tissue Cu concentrations did not drop in the
      supplemented treatments when compared to controls. At adequate levels of dietary
      Zn, bioavailability of supplemental Zn sources may be less important than under
      conditions of limited dietary Zn or if very high levels of supplemental Zn are
      fed.

PMID- 9021669
TI  - [Immunotoxic effects of a new antineoplastic agent S-1 in mice--comparison with S
      1, UFT and 5-FU].
AB  - The immunotoxicity of S-1, which is a new antineoplastic agent, was investigated
      in BALB/c mice. S-1 contains tegafur (FT), CDHP, and potassium oxonate (Oxo) in a
      molecular ratio of 1:0.4:1. 5-fluorouracil (5-FU) and UFT were used as reference
      drugs. S-1 and reference drugs were administered by oral gavage for 7 days. The
      high dose employed in this study was determined as the maximally tolerated dose
      of a 9-day repeated-dose study in sarcoma 180-bearing mice. Decreased body weight
      was observed in mice treated with 5-FU and UFT but not in those treated with S-1.
      A significant decrease in thymus and spleen weight was observed in S-1-, UFT- and
      5-FU-treated mice, and the degree was same for the three drugs. Though the number
      of white blood cells decreased dose-dependently for the three drugs, S-1 had the
      weakest effect. The number of red blood cells also decreased, but the effect was
      not dose-dependent, and its magnitude was the same for the 3 drugs. S-1 induced a
      dose-dependent decrease in the IgM antibody PFC response to sheep erythrocytes.
      The delayed type hypersensitivity response used a footpad reaction method was
      significantly suppressed at the highest dose of S-1. 5-FU and UFT suppressed
      humoral and cell-mediated immunity in almost the same manner as S-1. The degree
      of suppressive effects was greater on the humoral immune response than on the
      cell-mediated immune response. The number of CFU-GM colonies was significantly
      decreased in the highest dose group of each drug and in a lower group as well in
      S-1-treated mice. This finding might reflect the fact that S-1 induced continuous
      high levels of 5-FU in the blood. Under these experimental conditions, S-1
      induced immunosuppressive effects in BALB/c mice, and the degree of suppression
      was almost same as that induced by 5-FU and UFT.

PMID- 9021671
TI  - Manganese levels in serum of healthy Venezuelan infants living in Merida.
AB  - Taking up where a previous paper had left off (10) the purpose of this study was
      to examine in further detail the serum concentration of manganese of 180
      apparently healthy Venezuelan infants (96 boys and 84 girls) ranging from 5 days
      to 12 months old, all residents of Merida. The flow injection analysis-atomic
      absorption spectrophotometric technique was used for the determination of
      manganese. The mean values of serum manganese were 0.42 +/- 0.12, 0.41 +/- 0.11,
      0.39 +/- 0.13, 0.39 +/- 0.1, 0.38 +/- 0.09, 0.37 +/- 0.11, 0.36 +/- 0.12 and 0.29
      +/- 0.10 microgram/L in infants 5 days and 1,3,5,7,10,11 and 12 months old,
      respectively. These values indicate that the average concentration of manganese
      in serum decreases with age, but the mechanism involved is not yet known, nor are
      the consequences of the decrease. The statistical analysis did not show any
      significant influence of sex on the serum value of the metal in the age range of
      5 days to 12 months.

PMID- 9021672
TI  - An evaluation of urinary measures of iodine and selenium status.
AB  - The aim of this study was to establish methodology for a survey of the iodine and
      selenium status of New Zealand residents, more specifically to investigate the
      correlation between fasting or random casual urine samples and 24 hour urines for
      iodine and selenium excretion. Sixty-two (31 M, 31 F) adults collected casual,
      fasting and 24 hour urine samples for analysis of iodide, selenium and
      creatinine. Plasma and serum samples were collected for analysis of selenium and
      glutathione peroxidase activity. Results indicated that fasting urine samples,
      but not casual urines, may give a reasonable estimate of urinary output of iodine
      and selenium on a population basis, but that 24 hour urines are necessary for
      diagnosis of iodine deficiency in an individual and for research purposes. The
      results for iodine also give no support for expressing iodine as the iodide
      creatinine ratio, although there was some indication that the selenium-creatinine
      ratio might be useful. Significant correlations between total daily excretion of
      selenium and iodine and also for urinary concentrations of the two trace elements
      in fasting and in 24 hour urine specimens may reflect a relationship of selenium
      and iodine to body size which may have implications for dietary requirements of
      these trace elements. Alternatively the correlations may reflect a relationship
      between dietary intake of the two trace elements in a country in which food
      concentrations are low, and this needs further investigation.

PMID- 9021673
TI  - Selenium and glutathione peroxidase reference values in whole blood and plasma of
      a reference population living in Valencia, Spain.
AB  - In order to assess the reference values for selenium nutritional status, adequate
      indicators (selenium concentration and glutathione peroxidase activity) were
      determined in whole blood and blood derivates of a healthy population (n = 287)
      from the province of Valencia, Spain. The reference population was selected by
      applying preestablished criteria. Selenium in whole blood and plasma was measured
      by graphite furnace atomic absorption spectrometry (GFAAS), with a deuterium
      correction, after addition of Pd/Mg(NO3)2 as the matrix modifier and appropriate
      dilution. Accuracy was checked by means of a reference material (Seronorm Trace
      Metals serum and whole blood). The population's reference intervals for selenium
      content at a 95% confidence level were: 53.03-108.96 and 66.71-119.4 mg/L for
      plasma and whole blood selenium concentration respectively. GPX activity was
      measured using a modification of the Paglia and Valentine method, and the
      reference intervals obtained ranged from 196 to 477 U/L in plasma, from 49 to 93
      U/gHb in erythrocytes and from 52 to 96 U/gHb in whole blood. The only
      statistically significant differences detected between men and women are for to
      the GPX activity in whole blood. The results obtained are in the range of values
      found by others authors in healthy populations residing in different European
      countries.

PMID- 9021674
TI  - Serum and tissue selenium contents related to renal disease and colon cancer as
      determined by electrothermal atomic absorption spectrometry.
AB  - Microwave digestion with nitric acid and hydrogen peroxide was applied to the
      determination of selenium in biological tissues by Electrothermal Atomic
      Absorption Spectrometry (ETAAS). Validation of this method is presented in terms
      of adequate recovery of selenium from standard reference materials and the method
      is applied to carcinogen human colon tissue. Ultramicrofiltration was used to
      study selenium protein binding and its fractionation and speciation in blood
      serum. These studies showed that 95% of the total selenium in serum seems to be
      bonded to high-molecular-weight proteins. Experiments with renal failure patients
      showed lower selenium levels than in the health population (0.57 +/- 0.23 mM
      versus 0.81 +/- 0.11 mM). A wider distribution pattern of total serum selenium
      concentration (from 0.1 to 1 mM) was clearly observed in renal failure patients.
      However, the ultramicrofiltrable selenium fraction was always constant, even in
      the presence of desferrioxamine (DFO).

PMID- 9021675
TI  - A comparison of the food composition table-based estimates of dietary element
      intake with the values obtained by inductively coupled plasma atomic emission
      spectrometry: an experience in a Japanese population.
AB  - In order to make quantitative comparison between food composition table-based
      estimates and instrumental measures by inductively coupled plasma atomic emission
      spectrometry (ICP-AES), total food duplicates were collected from 232 adult women
      in 10 study regions in 9 Prefectures in Japan. Daily dietary intake of 5
      elements, sodium (Na), potassium (K), phosphorus (P), calcium (Ca) and iron (Fe),
      were estimated from the weights of food items in each duplicate by use of food
      composition tables. Parallel to this the intakes were measured by wet-ashing of
      food duplicate homogenates followed by ICP-AES analysis. Because the emission
      intensity of K was significantly modified by Na co-present at various
      concentrations, K was measured after Na concentration was reduced to the value
      150 mg/L by dilution. The comparison of the two sets of the results, the
      estimated values and the measured values, showed that the estimated values were
      significantly larger than the measured values in the cases of Na, K, Ca and P
      (the ratio of the estimated to the measured values: 118% for Na, 115% for K, 109%
      for Ca; and 130% for Fe), whereas the two values essentially agreed with each
      other in the case of P (ratio: 93%). The differences were too large for any
      nutritional evaluation to be made when the method of Bland and Altman is applied.
      The significance of the differences in relation to nutritional evaluation of
      element intake is discussed.

PMID- 9021676
TI  - Aspects of protein bound copper in sheep plasma and its release in vitro
      especially after treatment with ammonium tetrathiomolybdate.
AB  - The distribution of protein-bound copper in sheep plasma between a globulin and
      an albumin fraction, as well as copper release in vitro by means of various
      agents, either from the above-mentioned fractions or from those formed after
      ammonium tetrathiomolybdate (TTM) treatment, were studied. Copper bound in both
      plasma globulin and albumin (CuGA) is 95.1% of the total plasma copper (CuT);
      copper release from the globulin fraction by means of trichloracetic acid (TCA)
      or cyanides (CN-) is relatively low, 17.1% and 25.8% respectively, while there is
      not any copper release after TTM treatment; however, the copper release from the
      albumin fraction by means of TCA and CN- is relatively high, 59.2% and 74.9%,
      respectively, while the treatment with TTM has the same effect of no copper
      release as mentioned above for the globulin fraction.

PMID- 9021677
TI  - Correlation of mercury and selenium in the human kidney.
AB  - The total mercury (Hg) and selenium (Se) concentrations were determined in kidney
      cortex samples of 195 deceased, non-occupationally burdened individuals. Mercury
      was determined by means of Cold-vapour Atomic Absorption Spectrometry (CV-AAS)
      and selenium by Graphite-Furnace Atomic Absorption Spectrometry (GF-AAS). The
      molar Se/Hg ratio is high (up to (a) 300) in cases with relatively low mercury
      concentrations [Hg]. The ratio decreases with increasing [Hg]. At [Hg] of 700
      1000 ng/g it reaches unity, where it remains constant even at larger [Hg]. Since
      in vitro mercury and selenium form relatively stable adducts, our results suggest
      the formation of a 1:1 Hg-Se compound that may explain mercury detoxification by
      selenium. This effect also results in the trapping of available selenium by
      mercury, too. Decreasing the reserve of free (i.e. not Hg-bound) selenium. The
      effect of this decrease of free selenium is under further investigation.

PMID- 9021678
TI  - The effects of fluorides and/or trace elements on the solubilities of enamel and
      cementum.
AB  - The purpose of this study is to determine the effects of fluorides and trace
      elements applied alone or in combination at different concentrations on the
      solubilities of enamel and cementum surfaces of the same teeth. The study has
      been performed on enamel and cementum surfaces of the impacted third molars
      extracted by surgical operation. Aqueous solutions of sodium fluoride, aluminum
      potassium phosphate, strontium chloride and titanium tetrachloride at different
      concentrations were applied to the surfaces. The solubilities of enamel and
      cementum and the depth of etchings have been calculated by means of the inorganic
      phosphorus in these etching solutions. According to the results, higher
      concentrations of fluoride and lower concentrations of strontium and titanium led
      to a significant reduction into solubilities of enamel and cementum. As certain
      combined applications of fluorides and trace elements decreased both of the
      enamel and cementum solubilities, it may be assumed that if such a treatment is
      beneficial during the adolescence of an individual, it may also be used when he
      is older.

PMID- 9021679
TI  - The graft-versus-leukemia effect of post-transplant donor leukocyte infusion.
AB  - Tumor relapse remains a major obstacle to the success of allogeneic bone marrow
      transplantation (BMT) as a treatment for leukemia. Due to limited treatment
      options, the outlook for most patients that relapse following allogeneic BMT has
      been poor. The infusion of normal immunocompetent leukocytes from the original
      marrow donor has become a promising new option for treating/preventing leukemia
      relapse in allogeneic BMT recipients. This form of treatment has often been
      referred to as donor leukocyte infusion (DLI) therapy. Our laboratory is using
      murine models of allogeneic BMT to address important unresolved issues regarding
      DLI therapy in an effort to make the treatment more effective. These include
      identification of the antileukemic effector cells, augmentation of the
      antileukemic effect, and understanding why graft-versus-host-disease (GVHD) is
      less severe than anticipated. This article reviews our work in murine models of
      DLI and introduces our current working hypotheses concerning DLI therapy.

PMID- 9021680
TI  - Immunomodulatory peptides with high binding affinity for class II MHC molecules
      for the prevention of graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) represents the major barrier to successful
      allogeneic bone marrow transplantation. Positive and negative selection studies
      have unequivocally demonstrated that donor T cells are responsible for the
      induction phase of GVHD. Inhibition of the early steps of T cell antigen
      recognition leading to graft-versus-host disease has become an area of intense
      investigation. Peptides with high binding affinity for class II MHC molecules
      have been shown to compete for the single class II binding site and to inhibit T
      cell proliferative responses in vitro. Recent work has extended this approach to
      the prevention of murine GVHD in vivo.

PMID- 9021681
TI  - T-cell-rich B-cell lymphoma--a distinct clinicopathologic entity?
AB  - T-cell-rich B-cell lymphoma is a particular variant of large B-cell lymphomas
      with the morphological hallmark of a small number of large neoplastic B-cells
      scattered in between a dense background of reactive T-lymphocytes, while
      histiocytes may be admixed in variable numbers. In the typical case, the
      neoplastic population resembles large germinal center cells including cells
      similar to the L+H-variants of Reed-Sternberg cells. The immunophenotype of these
      tumour cells is L26 + Leu-M1-BerH2-. Apart from these unifying features, the
      individual cases constitute a broad spectrum of various growth patterns, so that
      a multiplicity of different relations to other types of malignant lymphomas are
      discussed in the literature. This occurs to such an extent that it may be
      doubted, that one deals with a distinct and separate lymphoma entity. Moreover, a
      close relationship exists between T-cell-rich B-cell lymphoma and lymphocyte
      predominant Hodgkin's disease, because there are striking similarities between
      the two, and, in addition, coexistence of T-cell-rich B-cell lymphoma with
      Hodgkin's paragranuloma has been reported. It, therefore, seems conceivable that
      T-cell-rich B-cell lymphoma represents a developmental stage of lymphocyte
      predominant Hodgkin's disease. Be that as it may: There is no doubt that,
      presently, the nosological position of T-cell-rich B-cell lymphoma is unsettled
      and still remains to be clarified.

PMID- 9021682
TI  - The clinicopathological features of anaplastic large cell lymphomas expressing
      p80NPM/ALK.
AB  - The classification of malignant lymphoma has been based on morphological and
      immunophenotypical findings for a long time. Recently, as chromosomal and genomic
      abnormalities which closely relate to the specific subtypes of lymphoma are
      revealed, these factors becoming much more important in the evaluation of
      differences in clinicopathological features of the various lymphoma subtypes.
      Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma
      (NHL) involving large CD30+ neoplastic cells, which occasionally carries the
      chromosomal translocation t(2;5)(p23;q35). We have recently found a novel
      hyperphosphorylated 80-kDa protein tyrosine kinase, p80 which is expressed
      specifically in human ALCLs with this translocation. Subsequent cDNA cloning
      showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene
      and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene.
      In order to clarify the clinicopathologic features of p80-carrying ALCLs, we
      developed an anti-p80 polyclonal antibody, which immunoprecipitated,
      immunoblotted and immunostained p80 specifically. When paraffin sections of 105
      cases of ALCL were stained using the anti-p80 antibody, 30 were shown to be p80
      positive Clinicopathological comparison between p80-positive and p80-negative
      ALCLs revealed that the p80-positive cases occurred in a much younger patient age
      group and that the patients showed a far better 5-year survival rate. These data
      suggest that p80-positive ALCL is a distinct entity and should be differentiated
      from p80-negative ALCL.

PMID- 9021683
TI  - DNA cell content studies in multiple myeloma.
AB  - Here the current studies in cell DNA content of plasma cells (PC), from multiple
      myeloma (MM) patients is reviewed, focusing on two complementary aspects the
      detection of clonal abnormalities and the identification of the proliferative
      rate of PC. There is accumulating evidence that the measurement of cell DNA
      content by flow cytometry (FCM) is a useful parameter in the clinical evaluation
      of MM patients. Between 50 and 70% of MM patients display DNA aneuploidy, the
      majority of them being hyperdiploid. Comparing hyperdiploid with diploid
      patients, the former seem to display a better prognosis. Fluorescence in situ
      hybridization studies have confirmed that there is a high incidence of numerical
      chromosome abnormalities in MM and that trisomies are significantly more common
      than monosomies (84% vs 14%). The most frequent gains can be seen in chromosome 9
      and 15 while the most common monosomies are those of chromosome 13 and X in
      females. The possibility of analysing the cell cycle distribution by using a
      propidium iodide (PI)/CD38 double staining technique may be an alternative to
      other more laborious methods of assessing the PC labelling index. Thus, patients
      with > 3% S-phase PC detected by FCM have an adverse prognosis and this parameter
      is one of the most important independent prognostic criteria for predicting
      survival in MM patients. Moreover, the number of S-phase PC, together with other
      prognostic factors, such as beta 2microglobulin, age and performance status can
      be a very useful tool for stratifying patients into groups in order to establish
      risk-directed therapeutic protocols.

PMID- 9021684
TI  - The involvement of the candidate proto-oncogene NFKB2/lyt-10 in lymphoid
      malignancies.
AB  - NF-kappa B transcription factors regulate the expression of a variety of genes
      involved in immune responses and cell growth. In higher vertebrates, the NF-kappa
      B family encompasses five distinct members. Three NF-kappa B proteins, p65/RelA,
      RelB, and c-rel/Rel, have high transactivating potential in addition to their DNA
      binding activity. Two subunits, NF-kappa B1p50 and NF-kappa B2p52, coded
      respectively by the NFKB1 and NFKB2 genes, may only have DNA binding activity.
      Moreover, p50 and p52 subunits are translated as precursors, respectively p105
      and p100, which can be processed into the mature active forms by the removal of
      their carboxy-terminal ankyrin domain. The five proteins share a homologous amino
      terminal domain (rel domain) involved in DNA binding, dimerization, nuclear
      transport, and binding of regulatory subunits. All members form homo- and
      heterodimeric complexes with different DNA binding specificity and
      transactivating potential. Structural alterations of some members of the NF-kappa
      B gene family have been observed in lymphoid malignancies. In particular, the
      NFKB2 gene, localized on chromosome 10q24, represents a candidate proto-oncogene,
      since it has been found rearranged in certain types of lymphoma and more commonly
      in cutaneous lymphoma. Molecular analysis indicated that these rearrangements may
      occur as a consequence of chromosomal translocations or small internal
      chromosomal deletions. Rearrangements cluster within the carboxy-terminal ankyrin
      domain of the NFKB2 gene leading to the production of carboxy-terminally
      truncated proteins which, in some cases, are fused to heterologous protein
      domains. Experimental data showed that these abnormal proteins are constitutively
      localized in the nucleus, have lost the transcriptional repressor functions
      typical of normal NF-kappa B2p52 and may be capable of transactivation activity.
      These findings suggest that abnormal NFKB2 proteins may contribute to
      lymphomagenesis by altering the NF-kappa B system, both quantitatively and
      qualitatively, and leading to the activation of specific subsets of kappa B
      controlled genes.

PMID- 9021685
TI  - Quercetin and the growth of leukemic progenitors.
AB  - The bioflavonoid quercetin (3, 3', 4', 5-7-pentahydroxyflavone) inhibits in a
      dose-dependent manner the in vitro growth of acute leukemias and enhances the
      anti-proliferative activity of cytosine arabinoside. Quercetin exerts a blocking
      action of cell transition from the G0/G1 to the S phase of the cell cycle. Acute
      myeloid leukemias (AML)-M3,-M4 and -M5, and acute lymphoid leukemias (ALL) were
      more sensitive to quercetin than AML-M1 and -M2 subtypes. The sensitivity of
      leukemic progenitors to the growth inhibitory effect of quercetin significantly
      correlated with their clonogenic efficiency. We postulate that quercetin exerts
      its growth inhibitory action by interaction with type II estrogen binding sites
      and subsequent induction of Transforming Growth Factor-beta 1 expression and
      secretion. Finally quercetin is synergistic with hyperthermia in inducing
      apoptosis of leukemic cells sparing normal stem cell progenitors. Taken together
      these results stress the potential role of quercetin in the treatment of acute
      leukemias and its in vitro use in purging procedures for autologous bone marrow
      transplantation.

PMID- 9021686
TI  - Interferon-alpha and its effects on the cytokine cascade: a pro- and anti
      inflammatory cytokine.
AB  - Interferon-alpha (IFN alpha) has emerged as an important regulator of growth and
      differentiation, affecting cellular communication and signal transduction
      pathways as well as immunological control. The efficacy of IFN alpha has been
      demonstrated in many different diseases of viral, malignant, angiogenic,
      allergic, inflammatory, and fibrotic origin. Cytokines are pleiotropic and
      redundant molecules showing a wide variety of biologic functions on various
      tissues and cells, and several different cytokines exert similar and overlapping
      functions on certain cells. Data gained in the last years support this view also
      for IFN alpha. Initially thought to have mainly immunomodulating and
      proinflammatory effects, recent data suggest that IFN alpha has several anti
      inflammatory properties. These newly identified anti-inflammatory and
      immunosuppressive functions may help to explain some of the IFN mechanisms.

PMID- 9021687
TI  - Selective homing of human leukemic B-cell precursors to specific
      lymphohematopoietic microenvironments in SCID mice: a role for the beta 1
      integrin family surface adhesion molecules VLA-4 and VLA-5.
AB  - We used a SCID mouse xenograft model to study the in vivo growth patterns of
      primary leukemic cells from six patients with newly diagnosed B-cell precursor
      (BCP) acute lymphoblastic leukemia (ALL), including two patients with t(1;19)
      ALL, two patients with t(4;11) ALL, and two patients with t(9;22) ALL. Leukemic
      cells from these six patients caused overt leukemia in SCID mice with extensive
      multiple organ involvement. Leukemic BCP from SCID mice xenografted with leukemic
      cells from two t(9;22) ALL patients expressed very high levels of both VLA-4 and
      VLA-5 regardless of the tissue of origin. By comparison, in SCID mice xenografted
      with leukemic cells from the two patients with t(1;19) ALL and two patients with
      t(4;11) ALL, leukemic BCP from the bone marrow samples expressed high levels of
      VLA-4 as well as VLA-5, whereas the vast majority of leukemic BCP in the liver or
      spleen samples expressed neither of these adhesion molecules at significant
      levels. These results suggest that the expression of VLA-4 and VLA-5 on t(1;19)
      or t(4;11) leukemia cells likely determines their binding capacity to bone marrow
      stroma and may affect their migration to extramedullary tissues. Our findings are
      in accord with and extend previous studies which demonstrated that extracellular
      matrix and integrins influence development, compartmentalization, and migration
      of BCP during B-cell ontogeny. The described SCID mouse model system provides a
      unique opportunity to study the adhesion receptors which regulate the selective
      homing of human leukemic BCP to specific SCID mouse organs.

PMID- 9021688
TI  - Addition of etoposide to initial therapy of adult acute lymphoblastic leukemia: a
      combined clinical and laboratory study.
AB  - The role of high-dose etoposide in the initial treatment of newly diagnosed adult
      ALL was assessed in a combined clinical and laboratory study. Therapy on protocol
      JH8802 consisted of two induction modules, module 1 containing prednisone,
      vincristine, high-dose etoposide and L-asparaginase (L-asp), followed by module 2
      containing cytarabine (Ara-C) and daunorubicin (DNR). Patients achieving a
      complete remission (CR) underwent bone marrow transplantation (BMT) or intensive
      maintenance therapy. Results were compared to the preceding protocol (JH8302),
      which was similar except for omission of etoposide and L-asp. The CR rate
      following module 1 was 45% on protocol JH8802 and 9% on protocol JH8302 (p <
      0.0002). Nonetheless, the two protocols had similar CR rates following module 2
      (69% on protocol JH8302; 77% on JH8802) and indistinguishable survivals.
      Laboratory investigations performed on blasts harvested prior to chemotherapy
      revealed two factors that could potentially contribute to decreased etoposide
      sensitivity in ALL blasts. A flow microfluorimetry-based assay of nuclear DNR
      accumulation detected small P-glycoprotein (Pgp)-mediated decreases in drug
      accumulation in a quarter of the samples. Western blotting demonstrated that
      topoisomerase II was present in all samples but was diminished in amount compared
      to the Molt3 human ALL cell line. Immunoperoxidase staining with affinity
      purified antibodies revealed that topo II alpha, the target for etoposide, was
      detectable in only a minority of the blasts (median 7.5%, range < 1-35%) at
      diagnosis. These observations raise the possibility that alterations in drug
      accumulation and diminished target enzyme levels might both limit the long-term
      efficacy of a single course of high dose etoposide administered early in the
      treatment of adult ALL.

PMID- 9021689
TI  - Month-of-birth and incidence of acute lymphoblastic leukemia in children.
AB  - As a means of examining the virus-relatedness of acute lymphoblastic leukemia
      (ALL) in children, we investigated the association between month-of-birth and the
      occurrence of ALL in 1487 children aged 0-15 years at the time of diagnosis. Our
      hypothesis being that evidence of seasonal variation in births of ALL cases would
      suggest exposure to a transmissible etiologic agent during the perinatal period.
      The data were obtained from the Surveillance, Epidemiology, and End Results
      (SEER) Program and consisted of children diagnosed during the years 1973-1986.
      Aggregate monthly incidence rates of ALL stratified by month-of-birth, for each
      SEER site, all sites combined, and for broad geographic regions were calculated.
      No evidence for an association between month-of-birth and childhood ALL was
      found.

PMID- 9021690
TI  - Etoposide and mitoxantrone as a second cycle of consolidation therapy following
      high dose cytosine arabinoside and daunorubicin in patients with acute non
      lymphocytic leukemia in remission: a pilot study.
AB  - High dose cytosine arabinoside (ARA-C) has produced long term relapse free
      survival in 26% to 49% of patients when used as consolidation therapy of acute
      non-lymphocytic leukemia (ANLL) in first remission. However, the optimal
      consolidation regimen has not been defined. In this pilot study we attempted to
      confirm and extend our previous studies of high dose consolidation therapy by
      administering two cycles of consolidation chemotherapy to patients with ANLL in
      first remission. The first cycle was high dose ARA-C 3 gm/m2 over 1 hour every 12
      hours for 12 doses followed by daunorubicin 45 mg/m2/day for three days. The
      second cycle was etoposide 75 mg/m2/day for 10 days and mitoxantrone 12 mg/m2/day
      for three days. Twenty-three patients received high dose consolidation
      chemotherapy, 13 of whom received the proposed two cycles. The major reason for
      not receiving the planned second consolidation cycle was life threatening
      toxicity, primarily fungal infection, during the first consolidation cycle. By
      actuarial estimate, 46% of patients receiving consolidation chemotherapy were
      projected to be relapse free at 36 months. There were no deaths during
      consolidation. Survival was not improved in patients receiving etoposide and
      mitoxantrone as the second cycle of consolidation therapy as compared to patients
      receiving only one cycle of consolidation therapy.

PMID- 9021691
TI  - Screening for multidrug resistance in leukemia: cell reactivity to MRK-16
      correlates with anthracycline retention and sensitivity of leukemic cells.
AB  - The biologic and clinical importance of the multidrug resistance (MDR) that is
      related with the overexpression of the P170 glycoprotein (Pgp) is widely
      recognized. However, a major issue that has not yet been solved is the definition
      of the degree of Pgp expression which is associated with a significant decrease
      of the sensitivity of the cells to chemotherapy. For this reason we studied the
      leukemic cells from 83 cases of acute leukemia. Leukemic cells were fixed in PLP
      and treated with saponine. Pgp expression was assayed by flow cytometry, using
      the anti Pgp monoclonal antibody MRK-16. Results were expressed both as the
      number of positive cells and by the intensity of the reaction as defined by the
      mean fluorescence index (MFI), i.e. the ratio between the mean fluorescence
      intensity of the MRK-16 incubated cells and of the IgG2a incubated cells. Thus,
      Pgp expression was compared with the results of two in vitro tests of cell
      sensitivity to anthracyclines, daunorubicin (DNR) cell retention and DNR
      cytotoxicity. We found that it was not the number of MRK-16 positive cells, but
      the degree of the reaction with MRK-16 (MFI) that significantly related to the
      anthracycline toxicity tests. Therefore, we propose that for clinical purposes a
      quick and cheap determination of Pgp-related MDR in leukemic cells may be
      obtained by measuring the MFI with MRK-16 in a standard flow cytometry assay and
      that the assay may indeed be sufficient to estimate Pgp expression as well as the
      influence of Pgp on cell sensitivity to anthracyclines.

PMID- 9021692
TI  - High-dose hydroxyurea and G-CSF to collect Philadelphia-negative cells in chronic
      myeloid leukemia: preliminary results.
AB  - Five patients with Ph+ chronic myeloid leukemia and no detectable diploid cells
      in the marrow received 6 g hydroxyurea twice daily for 7 days followed by G-CSF
      to harvest Ph-cells 1-84 months after diagnosis. Three were in first chronic
      phase, and two in accelerated phase. One stopped hydroxyurea after 4 doses due to
      intractable vomiting and was not apheresed, while two stopped hydroxyurea after 9
      and 11 doses because of mucositis and skin rash. Two tolerated all doses; one
      with no significant side effects, and one with mucositis and painful plantar
      rash. The nadir leukocyte, neutrophil, and platelet counts were 0.4-0.8, 0-0.1,
      and 2-19 x 10(9)/L respectively. Apheresis was commenced when the leukocytes were
      1.2-3.8 x 10(9)/L 9-10 days after starting G-CSF, and 6 aphereses were performed.
      Four collections were 100% Ph+, and two 22% and 90% Ph-. The total nucleated
      cell, CD34+/CD34-subset, CD34+/CD33+ subset, and CFU-GM yields per kg per
      collection were 0.48-2.38 (median 1.18) x 10(8), 0-0.48 (median 0.012) x 10(6),
      0.028-10.19 (median 0.92) x 10(6), and 0.29-41.81 (median 21.78) x 10(4)
      respectively. We conclude that hydroxyurea in the dose we used is poorly
      tolerated, and is associated with significant adverse effects including severe
      myelosuppression. It is possible to harvest diploid cells during recovery, but
      achievement of Ph-negativity appears to be erratic and cell yields are poor.

PMID- 9021693
TI  - Retinoic acid syndrome: pulmonary computed tomography (CT) findings.
AB  - We report the pulmonary computed tomography (CT) findings in three patients with
      acute promyelocytic leukaemia who developed the retinoic acid syndrome following
      all-trans retinoic acid (ATRA) therapy. The most consistent CT findings were
      small, irregular peripheral nodules in the lung fields and pleural effusions. Two
      of the patients also showed evidence of reticular and ground glass shadowing as
      well as abnormal anterior mediastinal soft tissue. We report for the first time
      an association between ATRA and pneumothorax. We conclude that routine CT
      scanning may provide a sensitive means of early detection or monitoring of the
      syndrome and thereby may facilitate its management.

PMID- 9021694
TI  - Clinical and prognostic implications of bone lesions in childhood leukemia at
      diagnosis.
AB  - We studied 168 children with acute lymphoblastic leukemia (ALL) and 57 with acute
      nonlymphoblastic leukemia (ANLL) by retrospectively analyzing clinical symptoms,
      bone or joint involvement, and hematological findings to verify the clinical
      features and prognosis of children with acute leukemia who showed radiographic
      bone changes at the time of diagnosis. Of these, 36 with ALL (21.4%) and 6 with
      ANLL (10.5%) had symptoms referable to the bones or joints. Thirteen patients
      (7.7%) with ALL showed bone lesions radiographically. Phenotypically, 12 of the
      13 had common ALL, 8 were incorrectly diagnosed and had received treatment for
      osteomyelitis or juvenile rheumatoid arthritis for 1 to 7 months prior to
      diagnosis of ALL. Leukocyte count was nearly normal with few or no blasts, and
      anemia and thrombocytopenia were mild or absent in all patients. Twelve of them
      remained in a complete remission for 26 to 148 months. Our data suggest that
      children with bone lesions related to acute leukemia exhibit clinical features
      that mimic infectious or collagen disease at diagnosis, and may belong to a
      subgroup of ALL with a better prognosis.

PMID- 9021695
TI  - Analysis of IL-2, IL-4 and their receptors in clonally-related cell lines derived
      from a patient with a progressive cutaneous T-cell lymphoproliferative disorder.
AB  - Three clonally related T-cell lymphoma lines (PB-1, 2A, and 2B) were examined for
      expression of IL-2, IL-4, and their receptors. All three lines were derived from
      a single patient who had an atypical, progressive T-cell lymphoproliferative
      disorder involving primarily skin (Davis, T.H. et al. 1992, N. Engl. J. Med.
      326:1115). The PB-1 cell line was obtained from a relatively early, clinically
      indolent stage of the cutaneous lymphoma, whereas the 2A and 2B lines were
      established from a late, aggressive stage of the lymphoma. Reverse-transcriptase
      PCR performed with primer pairs specific for IL-2 and IL-4 showed that no mRNA
      coding for these cytokines was present in any of the lines with the exception of
      IL-4 mRNA in the 2A line. No IL-4 protein, however, was found in any of the cell
      lines including 2A by immunocytochemical staining with anti-IL-4 mAb.
      Accordingly, no bioactive IL-4 was present in the supernatants of these lines. In
      contrast, all three T-cell lymphoma lines contained mRNA for IL-2R alpha, IL-2R
      beta, IL-4R and common gamma chain. Immunocytochemical analysis revealed that
      only the PB-1 line stained strongly with mAbs specific for IL-2R alpha, IL-2R
      beta, and IL-4R whereas the 2A and 2B lines showed only limited staining with
      these mAbs. In contrast to expression of IL-2R alpha and IL-4R primarily on the
      cell surface, IL-2R beta was localized mainly in the cell cytoplasm. Testing
      supernatants of the cell lines by ELISA for the presence of soluble alpha chain
      of the IL-2R (sIL-2R) has shown that only PB-1 secreted a large amount of sIL-2R,
      whereas the 2A and 2B lines secreted lesser amounts. Furthermore, the PB-1 cells
      expressed a relatively large number of IL-4R as determined by IL-4 binding
      studies using an IL-4-alkaline phosphatase fusion protein. The remaining two
      lines displayed only limited binding of IL-4. Addition of IL-2 and/or IL-4 to the
      culture medium did not modulate growth of PB-1 and the other two lines. These
      findings may indicate that at least some types of T-cell lymphoma evolve from
      cells which lose the capacity to synthesize T-cell autocrine growth factors such
      as IL-2 and IL-4, and show progressive loss of receptors for these cytokines.

PMID- 9021696
TI  - The COP regimen is not a feasible treatment for advanced, refractory chronic
      lymphocytic leukemia.
AB  - The COP regimen has been widely used as a second-line treatment for advanced
      chronic lymphocytic leukemia (CLL). In this retrospective analysis of COP therapy
      24 patients with CLL were included. All but two patients had previously been
      treated with alkylating agents and had become refractory to the therapy. The
      overall response rate to COP was 25%. Three patients had CR (12.5%), three PR
      (12.5%), five SD (21%), four PD (17%), and nine patients died (37.5%) during the
      COP treatments. The cause of death was neutropenic sepsis in all cases. The
      median duration of responses was 18 months. The median survival of all patients
      was 9.5 months. The survival of responders was 24.5 and of non-responders only
      5.5 months. The COP regimen seems to have low efficacy in the treatment of
      refractory CLL and the toxicity of this regimen in the late disease phase appears
      to be unacceptable.

PMID- 9021697
TI  - Bcl-x gene expression in Hodgkin's disease.
AB  - Bcl-x is a Bcl-2-family protein that has been previously detected in cortical
      thymocytes, plasma cells, and activated lymphocytes. We report here on the high
      detection rate of the Bcl-x protein found in 86% of Hodgkin's disease samples and
      on the significance regarding its complex role among the Bcl-2-family of
      proteins: Bcl-x is known to heterodimerize with Bcl-2 (an anti-apoptosis protein)
      and with Bax, a potent inducer of cell death. Moreover, recent evidences show
      that Bcl-x may induce multiple drug resistance in vitro, suggesting that chemical
      or biological interactions with this protein may have potential therapeutic value
      in Hodgkin's disease.

PMID- 9021698
TI  - Autologous bone marrow transplantation in 44 patients with aggressive non
      Hodgkin's lymphoma at University "La Sapienza" of Rome.
AB  - High dose therapy followed by infusion of autologous bone marrow has become a
      major treatment option for an increasing number of poor prognosis non-Hodgkin's
      lymphoma (NHL) patients. In our study we analyzed the outcome of autologous bone
      marrow transplantation (ABMT) in 44 high grade NHL patients transplanted at our
      institution between 1985 and 1992. Median age was 31 years (range 12-61);
      nineteen were in partial remission (PR) after first line chemotherapy and 25 in
      sensitive relapse (SR). Of the 25 patients transplanted in SR, 14 relapsed after
      a median time of 5.5 months (range 1-26), 8 are in complete remission after a
      median follow up of 41.5 months and three died from toxicity. Of the 19 patients
      grafted in PR, 11 are alive and progression free after a median follow up of 52
      months, while 8 relapsed at a median time of 5 months. The overall progression
      free survival (PFS) projected at 6 years is 35% with a 47% PFS for patients
      transplanted in PR and 28% for patients in SR. In conclusion, high dose therapy
      and ABMT has achieved widespread use as salvage therapy for patients with
      relapsed/refractory high grade NHL. In particular, our experience confirms that
      myeloablative treatment is a safe and well tolerated procedure for patients in
      PR, that may be easily applied as early salvage therapy without major toxicities.

PMID- 9021699
TI  - Clinically-occult mixed cellularity Hodgkin's disease with Charcot-Leyden
      crystals.
AB  - Charcot-Leyden crystals (CLC) are rarely described in tissue. Because of the
      derivation of CLC from eosinophils, and the antineoplastic functions that
      eosinophils effect, it is plausible that CLC in neoplastic tissue specimens may
      be significant. We recently encountered a case in which Hodgkin's disease and CLC
      were unexpectedly found. We reviewed 31 cases of Hodgkin's disease for CLC and
      sought relationships between CLC incidence and morbidity or mortality. While
      various grades of eosinophilia were represented, CLC were encountered only in the
      case reported. The role of eosinophils and CLC in Hodgkin's disease is enigmatic.
      With clinicopathologic correlations from additional patients, it may be
      determined that CLC play a role in the natural history or prognosis of Hodgkin's
      disease.

PMID- 9021700
TI  - Stepdown single agent antibiotic therapy for the management of the high risk
      neutropenic adult with hematologic malignancies.
AB  - The standard of therapy for the high risk adult neutropenic host being treated
      with broad spectrum antibiotics for fever has been to continue intravenous
      antibiotics until neutropenia resolves. We performed a small, limited pilot study
      to determine if it is safe to switch these patients to oral monotherapy with
      ciprofloxacin. Ten patients with hematologic malignancies who had < or = 108
      granulocytes/mm3 after cytoreductive therapy and were afebrile for at least five
      days had intravenous antibiotics discontinued and were placed on oral
      ciprofloxacin. Eight patients were able to be discharged from the hospital and
      seven were treated without the need for reinstitution of intravenous therapy. Of
      the three failures, one developed fever with a new bloodstream infection and two
      developed fever with relapse of leukemia. Patients remained on ciprofloxacin an
      average of 14.5 days (range 4 to 35 days). Aggregate cost savings for the 10
      patients from this approach were estimated to be $11,400 for antibiotics and
      $88,800 for hospitalization. If corroborated in larger, randomized studies, the
      use of "stepdown monotherapy" may be a cost effective approach to the management
      of the stable neutropenic patient.

PMID- 9021701
TI  - Metastatic seminoma simulating malignant lymphoma in an HIV infected hemophiliac.
AB  - Although most common, malignant lymphoma and Kaposi's sarcoma are not the only
      malignancies encountered in lymph nodes from HIV-infected patients. An increased
      frequency of testicular germ cell tumors in HIV-infected individuals has been
      reported. We report here the first case, to our knowledge, of a metastatic
      seminoma in an HIV-infected hemophiliac. The atypical clinical presentation,
      cervical and axillary adenopathy, simulated malignant lymphoma. The diagnosis was
      first suspected when a fine needle aspiration biopsy from an enlarged cervical
      node revealed a mixture of benign appearing lymphocytes and loosely cohesive
      large tumor cells in a "tigroid" background. Immunocytochemistry and a subsequent
      excisional biopsy confirmed the cytologic diagnosis. Metastatic germ cell tumors
      should be considered in the differential diagnosis of HIV-related
      lymphadenopathy.

PMID- 9021703
TI  - Royal Marsden teaching cases. An elderly man with weight loss and anaemia.

PMID- 9021704
TI  - Lack of prognostic value of CD34 in adult AML.

PMID- 9021702
TI  - Infantile acute monocytic leukemia with tumor formation in the skin expressing
      adhesion molecules as seen by electronmicroscopy.
AB  - We report a case of infantile acute monocytic leukemia associated with solid
      tumors in the skin. Light microscopy showed that the tumor cells were mainly
      spindle-shaped and arranged in tandem. Immunohistochemical staining showed that
      fibronectin was detected in the extracellular matrix (and partially on the
      surface of tumor cells), integrin alpha 5 beta 1 on the cell surface, and
      vinculin and actin were detected in the cytoplasm of the tumor cells. Electron
      microscopy showed that the tumor cells had perpendicular transmembranous fibrils
      and closely situated collections of cytoplasmic microfilaments beneath the cell
      membrane suggesting fibronexus-like structures. We conclude that the expression
      of fibronectin, integrin alpha 5 beta 1, vinculin, cytoplasmic actin and
      fibronexus-like structure in leukemic cells indicate these cells possess an
      adhesive function. The mechanism of formation of the extramedullary solid tumors
      in this patients involved these adhesion molecules of the tumor cells.

PMID- 9021705
TI  - Why do drugs work in CLL?

PMID- 9021707
TI  - Cellular/cytogenetic events in CLL.

PMID- 9021706
TI  - What is the CLL B-lymphocyte?

PMID- 9021708
TI  - What does apoptosis mean in CLL?

PMID- 9021709
TI  - Innovative strategies for the treatment of CLL.

PMID- 9021710
TI  - Current strategies for the treatment of CLL.

PMID- 9021711
TI  - Determination of functional portal-systemic shunting in patients submitted to
      hepatic angiography.
AB  - Angiographic visualization of the hepatic vascular bed by selective angiography
      can be profitably complemented with the evaluation of functional portal-systemic
      shunting by D-sorbitol bioavailability. Seventeen patients requiring diagnostic
      arterial catheterization were studied: most of them had biopsy-proven liver
      cirrhosis. Patients were studied at rest and after overnight fasting on two
      subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol
      was administered by direct infusion (15 mg/min for 20 min) into the superior
      mesenteric artery and an antecubital vein, respectively. The fractional
      bioavailability (Fma) of D-sorbitol was calculated as the ratio between the net
      cumulative urinary outputs obtained after infusion through the catheter into the
      superior mesenteric artery and the systemic vein, respectively. A good
      correlation was found between the estimated fractional portal-systemic shunting,
      which in the present study ranged between 1.4% and 96.7%, and a suitable index
      scoring the clinical evidence of collateral circulation. Since the hepatic
      removal of D-sorbitol is not affected by sinusoidal capillarization and its
      hepatic extraction ratio is quite high and only slightly modified by reduction in
      the number or functional activity of hepatocytes, the measured Fma can be assumed
      as a parameter reflecting the entity of portal-systemic shunting. The test is
      safe and inexpensive, and appears potentially useful in several situations in
      which portal-systemic shunting is pathophysiologically relevant.

PMID- 9021712
TI  - Hepatitis C virus serotypes and liver pathology.
AB  - The present study aimed to analyze the pathology of chronic hepatitis C in
      relation to HCV serotype, and to speculate on possible differences in the
      pathogenesis of liver injury. Liver biopsies were investigated from 59
      consecutive patients in whom hepatitis C virus genotypes were determined by a
      serological genotyping assay that detects antibodies directed to epitopes encoded
      by the NS4 region. A morphological study was performed in each case,
      semiquantitatively scoring necro-inflammatory and fibrotic liver lesions. The
      prevalence of HCV serotypes was as follows: 26 of the 59 patients (44%) had type
      1 infection, 11 (19%) had type 2 and 20 (35%) had type 3. A significant
      association between intravenous drug abuse and serotype 3 infection was observed.
      Patients with HCV type 2 proved significantly older than patients with infection
      type 1 or 3, and more frequently they showed a more active liver disease, but no
      differences were found in the quality and acinar topographic distribution of all
      the morphological lesions scored. In conclusion, in chronic hepatitis C a more
      active liver disease can be related to HCV serotype 2 but the spectrum of liver
      lesions is independent of HCV types. From a morphological point of view, a
      different pathogenesis of liver injury related to different HCV types is
      unlikely.

PMID- 9021713
TI  - Expression of mRNA encoding intestinal type alkaline phosphatase in rat liver and
      its increase by fat-feeding.
AB  - The presence of types of alkaline phosphatase (ALP) other than the tissue non
      specific type enzyme in rat liver and its increase by fat feeding are known. In
      order to examine expression of intestinal type ALP in liver, specific
      oligonucleotide primers corresponding to two types of mRNAs of rat intestinal ALP
      (RTIN-1 and -2) were designed and amplified by means of the reverse transcriptase
      polymerase chain reaction (RT-PCR). It was found that RTIN-1 mRNA was expressed
      only in the intestine but not in the liver, while RTIN-2 mRNA was expressed both
      in the intestine and in the liver. By fat feeding, expression of RTIN-1 mRNA
      increased in the intestine and that of RTIN-2 mRNA increased both in the
      intestine and in the liver. Thus, it was concluded that rat liver expressed one
      of the intestinal type ALP (RTIN-2) which was enhanced by fat feeding.

PMID- 9021714
TI  - Localization of hyaluronan in human liver sinusoids: a histochemical study using
      hyaluronan-binding protein.
AB  - Circulating hyaluronan is mostly derived from lymph, fibroblast and Ito cells in
      the liver, and more than 90% of hyaluronan is degraded in hepatic sinusoidal
      endothelial cells. Thus, elevated serum hyaluronan is regarded as an indication
      of hepatic fibrosis with activated Ito cells and dysfunctional sinusoidal
      endothelial cells. We studied the distribution of hyaluronan in human liver
      sinusoids to determine the influences on elevated hyaluronan levels in sera.
      Histochemical examination was made using hyaluronan-binding protein (HABP) and
      serial sections of liver tissue for staining of alpha-smooth muscle actin (ASMA)
      (an indicator of activated Ito cells) and of ulex europaeus agglutinin I lectin
      (UEA-1) (closely related to hepatic sinusoidal capillarization). Positive
      staining, indicating the presence of hyaluronan, was noted in fibrous regions
      around the portal tracts, areas of focal necrosis in the liver parenchyma, and
      walls of the sinusoids in chronic hepatitis. In this group, hyaluronan-positive
      areas corresponded to positive ASMA staining and faint staining of UEA-1. On the
      contrary, in liver cirrhosis, UEA-1-positive areas were essentially identical to
      hyaluronan-positive areas and to ASMA-negative areas in sinusoidal walls.
      Hyaluronan and ASMA could be detected in the same areas of sinusoidal walls in
      chronic hepatitis, but not in liver cirrhosis. Hyaluronan appears to be mainly
      related to the staining of activated Ito cells in chronic hepatitis. Therefore,
      we concluded that in chronic hepatitis, the production of hyaluronan was
      accelerated in Ito cells; however, degradation of hyaluronan by sinusoidal
      endothelial cells continued. On the contrary, in liver cirrhosis, hyaluronan
      production decreased in Ito cells, and a marked transformation of sinusoidal
      endothelial cells with hepatic sinusoidal capillarization indicated loss of the
      ability to degrade hyaluronan. These different mechanisms in chronic hepatitis
      and liver cirrhosis may operate in the sinusoidal walls and may cause the
      elevation of hyaluronan in sera.

PMID- 9021715
TI  - Hepatocellular carcinoma in long-term oral contraceptive use.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies in certain
      parts of the world, particularly in Africa and Asia, but it is less commonly
      encountered in the United States. It is closely associated with chronic hepatitis
      B virus (HBV) and hepatitis C virus (HCV) infections, and almost always develops
      in a cirrhotic liver. In non-cirrhotic livers, HCC is found in about 20% of
      asymptomatic carriers of HBV and rarely in patients taking androgenic-anabolic or
      oral contraceptive (OC) steroids. We report four patients, who developed HCC
      after prolonged use of OC steroids. Whether OC steroids act as mutagen or co
      carcinogen in hepatocarcinogenesis is not clear. To exclude latent HCV and HBV
      infections which may occur in the absence of their serological markers, we
      employed polymerase chain reaction for the detection of HBV and HCV sequences in
      the tumor and non-tumorous liver tissue. Viral sequences of HBV and HCV were
      undetectable in all four cases. These findings suggest OC use as the only known
      risk factor in these cases and, therefore, strengthen its possible role in
      hepatocarcinogenesis.

PMID- 9021716
TI  - Hospital prevalence of asymptomatic primary biliary cirrhosis: 4-year study based
      on analysis of 4468 consecutive in-patients.
AB  - To assess the hospital prevalence of asymptomatic primary biliary cirrhosis
      (PBC), routine determination of serum alkaline phosphatase (AP), liver function
      tests (albumin, bilirubin, prothrombin time) and serum liver biochemistry
      (aminotransferases, gamma-glutamyltranspeptidase) were performed in 4468
      consecutive in-patients (2332 men, 2136 women; mean age 57 years, range 16-94
      years) admitted to our medical department from April 1991 to May 1995. In
      patients with an increase of serum AP levels, antimitochondrial antibody (AMA)
      testing, ultrasonography or CT scan, HIDA biliary scintiscan, bone scintiscan and
      endoscopic retrograde cholangio-pancreatography (ERCP) were performed to exclude
      any disorders other than PBC. Fourteen out of the 4468 patients (0.3%) showed an
      asymptomatic increase of AP levels (i.e., detected by chance at the entry and not
      earlier investigated). In 12 of 14 cases the increase of AP was not related to
      PBC. Asymptomatic PBC was found in 2 of 4468 patients (0.04%). When only the
      "risk group" (women over 40 years) is considered, the prevalence rate increases
      to 0.12% (2/1644 women). Our data, while not assessing the true prevalence of
      asymptomatic PBC in the general population, suggest that symptomless PBC is much
      more common than has been thus far supposed.

PMID- 9021717
TI  - Rsa I polymorphism at the cytochrome P4502E1 locus is not related to the risk of
      alcohol-related severe liver disease.
AB  - Ethanol-inducible cytochrome P4502E1 is the main pathway in the non-alcohol
      dehydrogenase oxidation of ethanol. Its coding gene, CYP2E1, is polymorphic at
      the Rsa I restriction site in the 5'-flanking region. The mutant genotype c2c2
      has a higher transcriptional activity than the genotype c1c1 or c1c2. Heavy
      drinkers carrying the c2 allele might be at a higher risk of alcoholic cirrhosis
      since they might synthesize greater amounts of acetaldehyde, the compound
      believed responsible for hepatotoxicity of ethanol. With the aim of establishing
      if the c2 allele increases the risk of cirrhosis in heavy drinkers, we studied 58
      (6 female) chronic heavy drinkers with liver cirrhosis and 137 healthy normal
      controls of the same ethnic (white Spaniards) origin. After extraction of DNA
      from white blood cells, alleles c1 and c2 of CYP2E1 were identified by
      restriction fragment length polymorphism (RFLP) with endonuclease Rsa I. Fifty
      six patients and 130 controls were classified as homozygous c1c1 and two and
      seven, respectively, as heterozygous c1c2. No homozygous c2c2 were detected. The
      c2 allele frequencies were 0.017 in patients and 0.026 in controls (non
      significant differences). We conclude that the Rsa I RFLP polymorphism is
      probably not related to the risk of cirrhosis in Spanish heavy drinkers.

PMID- 9021718
TI  - No significant influence of HLA determinants on susceptibility to hepatitis C
      virus infection in Caucasian patients with end-stage renal disease.
AB  - In hepatitis C, both susceptibility to infection and the course of disease may
      depend on differences in the immune response. As the major histocompatibility
      complex (MHC) plays a crucial role in antigen presentation, we investigated a
      possible relationship between susceptibility to hepatitis C virus (HCV) infection
      and human leucocyte antigen (HLA) alleles. Therefore, phenotype frequencies of
      HLA were compared in 186 anti-HCV positive patients with end-stage renal disease
      (ESRD) to 328 anti-HCV negative patients with ESRD. HLA class I alleles were
      determined serologically and HLA class II alleles (DRB1, DQA1, DQB1) by the
      polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) technique.
      Additionally, in anti-HCV positive patients we looked for a relationship between
      the activity of hepatitis C (indicated by elevation of transaminases or the
      presence of viremia) and HLA determinants. For the three criteria (antibody
      status, elevation of transaminases and viremia) a significant association to HLA
      alleles was not found in patients with ESRD. This suggests that neither
      susceptibility to HCV infection nor the biochemical activity of hepatitis and HCV
      RNA positivity seem to be strongly related to HLA status in Caucasian patients
      with end-stage renal disease.

PMID- 9021719
TI  - Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon
      efficacy in chronic hepatitis C.
AB  - To investigate the relationship between intrahepatic cytokine expression and
      interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1
      beta, -2, -4, -6, -8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha
      and TNF-beta mRNAs were investigated semiquantitatively by reverse transcription
      polymerase chain reaction using serial liver biopsies taken before and after IFN
      alpha treatment from 24 patients with CH(C), including 12 responders and 12 non
      responders. Before IFN treatment, IL-2, TNF-beta, IFN-gamma and IL-8 mRNA were
      associated with severe hepatitis activity whereas IL-4 mRNA was associated with
      weak hepatitis activity, regardless of IFN response. IL-2, TNF-beta and IFN-gamma
      mRNAs were significantly greater in IFN non-responders. After IFN treatment a
      complete response to IFN was significantly associated with the disappearance of
      these pro-inflammatory cytokines, whereas non-responders retained the expression
      of cytokine mRNA as before IFN treatment. Our results indicated that IFN-alpha
      treatment may modulate the intrahepatic cytokine network, and this may be one
      mechanism of IFN-alpha that reduces hepatitis activity, aside from an anti-viral
      effect. A difference in cytokine network may be involved in IFN response in
      CH(C).

PMID- 9021720
TI  - gamma-Glutamyl transpeptidase in normal and neoplastic prostate glands.
AB  - gamma-Glutamyl transpeptidase (GGT) is a cytoplasmic membrane-bound enzyme
      important in the metabolism of glutathione and other gamma-glutamyl compounds. It
      is present in highest levels in the kidney and is also expressed prominently in
      reproductive organs such as the prostate gland. Because GGT has never been
      examined in prostatic carcinoma, we used a new polyclonal antibody (GGT 129) for
      immunohistochemical localization of GGT in normal prostate gland and 72 prostatic
      carcinomas. The normal lining secretory cells of ducts and acini showed apical
      immunoreactivity for GGT, but the basal epithelial cells were negative. Most of
      the prostatic adenocarcinomas had GGT staining patterns and intensity similar to
      those of normal prostatic secretory cells, because the majority of neoplastic
      cells showed immunopositivity in more than 80% of the adenocarcinomas. In
      comparing the percentage of cells staining for GGT with clinicopathologic
      parameters, there was no correlation between the number of positive cells and the
      Gleason score, the percentage of intraglandular carcinoma, capsule penetration,
      or seminal vesicle invasion. Immunostaining for GGT lacks value as a prognostic
      factor and does not correlate with standard clinicopathologic parameters. GGT may
      be important, however, for growth and maintenance of both normal and neoplastic
      prostatic cells. Modulating GGT levels or administering drugs that can be
      activated by GGT may have therapeutic value.

PMID- 9021721
TI  - Immunoelectron microscopic demonstration of regulated pathway for calcitonin and
      constitutive pathway for carcinoembryonic antigen in the same cells of human
      medullary carcinomas of thyroid glands.
AB  - The human medullary carcinomas are well known to secrete calcitonin (CT) as a
      neuroendocrine peptide and carcinoembryonic antigen (CEA) as a serum protein that
      is integrated into the cell membrane. This ultrastructural study is designed to
      elucidate whether CT and CEA are secreted via two different intracellular
      secretory pathways, a regulated pathway and a constitutive pathway. The
      immunoelectron microscopic postembedding method, performed on four cases of the
      human medullary carcinomas of the thyroid using plastic embedding material,
      disclosed two distinct different localization patterns for CT and CEA. CT was
      localized exclusively in dense cored secretory granules. CEA was present in the
      cell membrane and in the secretory vesicles. The secretory granules were
      completely negative for CEA. The trans-Golgi networks were also positive for CT
      and CEA. Electron microscopic double staining confirmed these localization in the
      same carcinoma cells. These observations suggest the presence of two distinct
      pathways in the endocrine cancer cells, i.e., the regulated pathway for CT and
      the constitutive pathway for CEA.

PMID- 9021722
TI  - The role of prognostic markers (MiB-1, RB, and bcl-2) in the diagnosis of
      parathyroid tumors.
AB  - Assessment of the malignant potential of parathyroid tumors in the absence of
      metastasis can be difficult using morphologic criteria alone. The role of
      prognostic markers that may assist in evaluating aggressive behavior in these
      tumors has not been fully studied. We performed a retrospective study of 31
      parathyroid lesions, including 10 adenomas, 10 atypical lesions, and 11
      carcinomas, to evaluate the diagnostic and prognostic role of the MiB-1, p53, RB,
      and bcl-2 markers by immunohistochemical techniques. The mean tumor proliferative
      fraction (TPF), expressed as the number of MiB-1-positive nuclei per 1000 cells,
      was 20.3 in adenomas (range, 5-51), 20.0 in atypical lesions (range, 8-36), and
      79.8 in carcinomas (range, 4-133). Only 1 of 20 benign lesions had a TPF more
      than 40, and only 2 of 11 carcinomas had a TPF less than 40. One atypical lesion
      and two carcinomas showed scattered cells positive for p53. Patients with the
      adenoma with increased TPF and the atypical lesion with positive p53 have been
      free of disease for 16 months. bcl-2 was expressed in 7 (70%) of 10 adenomas, 2
      (20%) of 10 atypical lesions, and 4 (36%) of 11 carcinomas. Two of the 11
      carcinomas were RB negative, whereas all of the 20 benign lesions were RB
      positive. We conclude that high TPF (greater than 40 as measured by staining with
      MiB-1) strongly correlates with malignancy and, therefore, may be useful in the
      diagnosis of carcinomas. Negative RB stain, although not a common event, may be
      helpful to exclude benign lesions. Other tumor markers (p53 and bcl-2) were not
      useful in distinguishing malignant from benign lesions.

PMID- 9021723
TI  - Non-Hodgkin's lymphoproliferative disorders involving the spleen.
AB  - One hundred eight splenectomy specimens involved by lymphoid neoplasms were
      studied to assess the frequency and pattern of involvement of the various disease
      groups. Cases were classified by the Working Formulation as well as by the
      Revised European-American classification of lymphoid neoplasms. Including the
      more recently described disease entities, large cell/immunoblastic lymphomas were
      the most common neoplasm, both primarily and secondarily, to involve the spleen
      (33.3% of all cases). The next most common lymphoid neoplasm to involve the
      spleen was chronic lymphocytic leukemia/ small lymphocytic lymphoma, found in
      19.4% of cases, followed by follicular center cell lymphoma (13.0%),
      lymphoplasmacytoid lymphoma (9.3%), splenic marginal zone lymphoma (8.3%), mantle
      cell lymphoma (6.5%), and hairy cell leukemia (6.5%). The remaining 3.7% of cases
      included T-cell proliferations and one difficult-to-classify mixed cell lymphoma.
      More than 95% of the cases could be placed into one of three morphologic patterns
      of splenic involvement, i.e., 57.4% of spleens were involved by predominantly
      white pulp disease, 20.4% by predominantly nodular disease, without a
      predilection for white or red pulp, and 17.6% by predominantly red pulp disease.
      Although the white pulp and nodular patterns were primarily, but not exclusively,
      B-cell disorders, specimens with predominantly red pulp disease included all of
      the cases of hairy cell leukemia, as well as cases of both B- and T-cell
      lymphomas.

PMID- 9021724
TI  - Molecular detection of bone marrow involvement in intravascular lymphomatosis.
AB  - Intravascular lymphomatosis (IVL) is an extremely rare variant of aggressive non
      Hodgkin's lymphoma characterized by confinement of neoplastic lymphocytes within
      vascular spaces. Although IVL is potentially curable with combination
      chemotherapy, diagnosis is often delayed, in part owing to the negative bone
      marrow biopsy specimens that are typical of this disorder. We hypothesized that
      use of a more sensitive method of analysis might identify small clonal B-cell
      populations in histologically negative bone marrow biopsy specimens from patients
      with IVL. With use of a recently described assay for immunoglobulin heavy chain
      gene rearrangement based on the polymerase chain reaction, we demonstrated clonal
      B-cell populations in histologically negative marrow specimens from five (100%)
      of five patients with IVL. None of these specimens demonstrated molecular
      evidence of the t(14;18) associated with follicular lymphoma, providing no
      evidence for a common derivation of IVL and follicular lymphoma. In summary,
      molecular analysis of routine bone marrow biopsy sepcimens from patients in whom
      the diagnosis of IVL is entertained may facilitate prompt recognition of a lympho
      proliferative disorder and thereby permit timely therapeutic intervention.
      Moreover, these findings suggest that despite histologically negative staging
      bone marrow biopsy specimens, IVL typically disseminates early in its course,
      thus arguing against the use of localized therapy in this disorder.

PMID- 9021725
TI  - DCC genetic alterations and expression in endometrial carcinoma.
AB  - DCC (Deleted in Colorectal Carcinoma) is a candidate tumor suppressor gene
      located on the long arm of chromosome 18. DCC was initially identified and cloned
      during a search for the target gene located in a region of 18q that demonstrated
      loss of heterozygosity (LOH) in 70 to 80% of colorectal cancers. More recently,
      the region of 18q harboring the DCC gene has been shown to undergo LOH in
      approximately 14 to 30% of endometrial carcinomas. These findings suggest that
      DCC may be a target of LOH in at least some endometrial carcinomas and,
      therefore, may have a role in the pathogenesis of this common malignancy of the
      female genital tract. To address this possibility, we analyzed 26 cases of
      endometrioid endometrial carcinoma for DCC LOH and alterations in an AT
      microsatellite repeat located in an intron of the DCC gene. LOH was detected in
      one case (4%). Allelic shifts at the DCC AT repeat were detected in five (19%)
      additional cases. We also evaluated DCC protein expression by immunohistochemical
      analysis in normal, hyperplastic, and neoplastic endometrial tissues. Three
      proliferative and five secretory endometria and one simple endometrial
      hyperplasia demonstrated staining for DCC. Four of the 26 endometrioid
      endometrial carcinomas for which frozen tissue was available, including at least
      one from each histologic grade, and a case of endometrioid carcinoma confined to
      the endometrium completely lacked detectable staining for DCC. Although DCC LOH
      was infrequent in endometrial carcinomas, alterations of the gene (LOH or AT
      repeat alterations) were not uncommon (23% of our cases). In addition, DCC was
      expressed in normal endometrial tissue, whereas expression was lost in all of the
      five endometrial carcinomas. The combination of the genetic alterations and loss
      of DCC protein expression suggests that inactivation of the DCC gene may play a
      role in the pathogenesis of endometrial carcinoma.

PMID- 9021726
TI  - Gelatinases and inhibitors of gelatinases in pancreatic islets and islet cell
      tumors.
AB  - Pancreatic islets contain trace amounts of zinc to form insulin dimer, and matrix
      metalloproteinases (MMPs) are single-chain zinc-containing metallo-enzymes. By
      immunocytochemically staining pancreatic tissue, which contained exocrine duct
      adenocarcinoma, normal islets were incidentally found positive for gelatinase-A
      (MMP-2) and gelatinase-B (MMP-9), and for tissue inhibitor of metalloproteinase 1
      and 2 (TIMP-1 and TIMP-2). Normal islets from five pancreata were exclusively
      stained for two each of gelatinases and TIMPs. Twenty-two islet cell tumors were
      also stained for pancreatic hormones, gelatinases, and TIMPs, which included
      insulinomas, gastrinomas, glucagonomas, pancreatic polypeptide-omas (PPomas), and
      nonfunctioning tumor. In general, islet cell tumors were weakly stained for
      gelatinases and TIMPs, compared with normal islets in the adjacent pancreatic
      tissue. No clear difference in staining intensity among five kinds of islet cell
      tumors was observed. The selective immunolocalization of gelatinases and TIMPs in
      islet cells and islet cell tumors may suggest possible a structure-function
      relationship among zinc, gelatinases-TIMPs, and pancreatic hormones.

PMID- 9021727
TI  - Expression of type I interferon receptor in solid tumors of childhood.
AB  - Interferon alpha (IFN alpha) is used as an antineoplastic agent, both in
      hematopoietic malignancies and in solid tumors, because of its immunomodulatory
      action and direct antitumor activity. IFN alpha binds to specific cell-surface
      receptors that mediate its biologic activity. We studied the expression of IFN
      alpha receptors in pediatric solid tumors by use of the monoclonal antibody
      IFNaR3, which specifically recognizes the alpha subunit of the IFN Type I
      receptor. In three cell lines derived from those tumors, we determined the
      structure of the receptors by affinity cross-linking and immunoprecipitation
      techniques, and we determined their ability to mediate an antiproliferative
      effect. All of the tumor specimens studied by immunocytochemical analysis,
      including neuroblastomas, primitive neuroectodermal tumors, and
      rhabdomyosarcomas, stained positive for the IFN alpha receptor antibody, although
      in some cases immunoreactivity was weak. The three cell lines, derived from a
      neuroblastoma, a primitive neuroectodermal tumor, and a Ewing's sarcoma,
      respectively, showed the same pattern of IFN alpha receptor expression, both by
      affinity crosslinking and immunoprecipitation assays. Treatment with IFN alpha of
      those cell lines induces growth inhibition in vitro. These results suggest that
      IFN Type I receptor might be expressed in most solid tumors of childhood and that
      its structure is identical to the receptor expressed by the majority of
      hematologic malignancies.

PMID- 9021728
TI  - Expression of surfactant protein B precursor and surfactant protein B mRNA in
      adenocarcinoma of the lung.
AB  - Surfactant protein B (SP-B) is a 79-amino acid, hydrophobic protein that plays
      important roles in surfactant function and homeostasis. SP-B is produced in the
      respiratory epithelium by proteolytic processing of a glycosylated precursor (pro
      SP-B) of relative molecular mass 42,000 to 46,000. To develop diagnostic markers
      for pulmonary adenocarcinomas, we examined the incidence and distribution of pro
      SP-B and SP-B mRNA in paraffin sections of 35 non-small cell lung carcinomas (15
      adenocarcinomas, 15 squamous cell carcinomas, and 5 large cell carcinomas), using
      immunohistochemical techniques and in situ hybridization. Fifteen nonpulmonary
      adenocarcinomas were used as controls. Pro-SP-B and SP-B mRNA were detected in
      60% and 53% of pulmonary adenocarcinomas, respectively. Expression was seen in
      adenocarcinomas with acinar, papillary, bronchioloalveolar, and solid growth
      patterns. Squamous cell and large cell carcinomas of the lung and nonpulmonary
      adenocarcinomas did not contain pro-SP-B immunoreactivity or SP-B mRNA. The
      specificity of SP-B gene expression in adenocarcinomas of the lung supports the
      usefulness of pro-SP-B and SP-B mRNA in the study and diagnosis of these
      neoplasms.

PMID- 9021729
TI  - Encephalitozoon cuniculi microsporidiosis: infection of the brain, heart,
      kidneys, trachea, adrenal glands, and urinary bladder in a patient with AIDS.
AB  - A female AIDS patient, dying with widely disseminated Encephalitozoon cuniculi
      microsporidiosis, cytomegalovirus (CMV) disease, and Pneumocystis carinii
      infection, is described. Indirect immunofluorescent antibody staining studies and
      molecular analyses identified the microsporidian as the dog strain of E.
      cuniculi. Autopsy revealed necrotizing microsporidiosis of the adrenal glands and
      kidneys, with lesser involvement of the brain, heart, trachea, urinary bladder,
      spleen, and lymph nodes. Cellular targets included macrophages, epithelium,
      endothelium, and cardiac myocytes. Spore detection was enhanced by Gram-staining,
      polarization, and fluorescence chitin stains. Central nervous system microglial
      nodules were present and either contained microsporidia, CMV, or no identifiable
      pathogen. CMV disease was most severe in the central nervous system, trachea,
      adrenal glands, and colon, whereas the Pneumocystis carinii infection was focal
      in the lungs, lymph nodes, and spleen. This is the first demonstration of
      Encephalitozoon microsporidiosis of the brain, heart, and adrenal glands in a
      patient with AIDS. E. cuniculi should be included in the differential diagnosis
      of disseminated opportunistic infections in patients with AIDS.

PMID- 9021730
TI  - Detection of mycobacterial DNA in formalin-fixed, paraffin-embedded tissue
      specimens by duplex polymerase chain reaction: application to histopathologic
      diagnosis.
AB  - Granuloma is a chronic inflammatory process associated with noninfectious agents
      or infectious diseases such as tuberculosis. Determination of the causative agent
      might be occasionally difficult in histopathologic sections. In this study, we
      examined 60 specimens of granuloma or inflammatory lesions that were originally
      diagnosed as 51 cases of granulomatous inflammation, 6 of leprosy, and 3 of
      atypical mycobacteriosis. The diagnoses in the last two categories were made both
      histologically and clinically. All of the sections and DNA were prepared from
      formalin-fixed, paraffin-embedded blocks. Histopathologic and immunohistochemical
      findings were compared with the results of duplex polymerase chain reaction (PCR)
      using two primers to amplify mycobacterial-common 383-base pair (bp) DNA and
      Mycobacterium tuberculosis-complex-specific 240-bp DNA. Six samples of leprosy
      and three of atypical mycobacteriosis showed the 383-bp but not the 240-bp band.
      Among the 51 specimens of granulomatous inflammations, nine showed no band of
      even the beta-globin, the cases being excluded from this analysis. The 42
      specimens of granulomatous inflammation were subdivided into three categories by
      PCR: (1) 383- and 240-bp positive; (2) 383-bp positive and 240-bp negative; and
      (3) both negative. Category 1 included 32 specimens (76.2%), being considered as
      tuberculosis. One specimen was classified into Category 2, indicating possible
      atypical mycobacterium. Category 3 included nine specimens, composed of five of
      sarcoidosis and four other agent-induced granulomas, when compared with
      histologic and clinical findings. These findings indicate that the PCR assay
      using DNA extracted from paraffin-embedded materials provides useful information
      to differentiate tuberculosis from other type of granulomas.

PMID- 9021731
TI  - Correspondence re: Chieco P, Van Noorden C. Letter to the editor [in re Rubin EM,
      Derose PB, Cohen C. Comparative image cytometric DNA ploidy of liver cell
      dysplasia and hepatocellular carcinoma. Mod Pathol 1994;7:677]. Mod Pathol
      1996;9:84-5.

PMID- 9021732
TI  - Predicting and preventing oral cancer.

PMID- 9021733
TI  - Sensitive peptide sequence analysis: a faster weigh-in for biomolecules.

PMID- 9021734
TI  - Malaria genome project gets a funding boost.

PMID- 9021735
TI  - TB research; entering the post-genomic era.

PMID- 9021736
TI  - Naturally occurring cancer in pet dogs: important models for developing improved
      cancer therapy for humans.
AB  - It has been said that "dog is man's best friend'. Comparative oncologists are
      demonstrating that pet dogs could hold the keys for advances in cancer treatment
      in people. Specific types of cancer that arise spontaneously in pet dogs could
      serve as important models of human cancer, having much greater similarity to
      their counterparts in humans than many currently used experimentally induced
      tumor models. In vivo models that are relevant to human cancer are greatly
      needed, particularly for evaluating new strategies for cancer therapy, such as
      augmentation of the immune system or blockade of the metastatic cascade. In
      addition, pet dogs could also be used to identify environmental carcinogens by
      acting as sentinels of cancer induced by these toxins.

PMID- 9021737
TI  - Neuroinflammatory disease. IBC meeting on neuroinflammatory disease: research and
      treatment strategies. London, UK, 17 and 18 September 1996.
AB  - The conference focused on the impact of neuroinflammation in several important
      neurological illnesses. The similarities between the diseases were clearly
      brought out. It is unlikely that a single treatment for inflammation will emerge
      that will be useful in such diverse conditions. However, those who attended the
      conference felt that emphasizing the common features of these diseases was very
      useful. This highly successful meeting was organized by Drs V. Hugh Perry and
      Andy Gearing.

PMID- 9021738
TI  - Growth factors in angiogenesis: current interest and therapeutic potential.
AB  - Angiogenesis, the process of new blood vessel development, is an essential
      component of the body's physiology and contributes to the pathogenesis of a
      variety of diseases such as benign and malignant neoplasia and rheumatoid
      arthritis. Failure of this physiological response is also important in
      abnormalities of wound healing in diseases such as duodenal ulceration and
      diabetes. Angiogenesis is controlled by a variety of factors that initiate,
      control and terminate this complex, multi-stage process. This review covers those
      factors that are exciting much interest currently and have potential for
      incorporation into clinical medicine.

PMID- 9021740
TI  - Antisense technology and prospects for therapy of viral infections and cancer.
AB  - Eighteen years ago, antisense oligonucleotide therapeutics that can selectively
      knock out disease-causing genes could easily have been viewed as science fiction.
      Yet today, through much persistence and focused investment, the technology has
      nearly evolved to the point of realization. A number of first-generation
      antisense compounds have entered human clinical trials. Some of these compounds
      appear to work by an antisense mechanism to inhibit the expression of disease
      causing genes, while others probably work by unanticipated, yet clinically
      beneficial, mechanisms. In this review, the current status of antisense
      oligonucleotide development will be described as it relates to two areas of
      concentrated effort: antiviral and anticancer applications.

PMID- 9021739
TI  - Control of virus-induced lymphoproliferation: Epstein-Barr virus-induced
      lymphoproliferation and host immunity.
AB  - Epstein-Barr virus (EBV) is a latent herpesvirus that is associated with a number
      of tumors. EBV-infected cells show three patterns of latency ranging from type 1,
      where only one EBV-encoded antigen is expressed, to type 3, where all nine latent
      cycle proteins encoded by EBV are expressed. Malignancies exhibiting the type 3
      latency pattern are highly immunogenic and occur only in immunocompromised
      patients. It has recently been shown that adoptive immunotherapy with EBV
      specific cytotoxic T lymphocytes is an effective therapy for such tumors.
      Immunotherapy strategies and approaches to increase tumor immunogenicity are now
      being evaluated in tumors expressing type 2 latency.

PMID- 9021741
TI  - Gene therapy strategies for leukemia.
AB  - A number of diverse gene therapy strategies are being evaluated in the search for
      novel therapeutic approaches to leukemia. Antisense oligonucleotides, ribozymes
      and retroviral vectors are approaches directed at the molecular mechanisms of
      cancer. Transfer of genes encoding cytokines and human leukocyte antigens (HLAs)
      could also be used to elicit immunity against tumor cells. Gene marking
      strategies have been useful in elucidating the biology of disease relapse after
      autologous bone marrow transplantation. Suicide genes, such as the herpes simplex
      thymidine kinase gene, have been used to modulate graft-versus-host disease after
      allogeneic bone marrow transplantation. Although gene delivery remains a major
      challenge to gene therapy, some modifications have been implemented to overcome
      this issue. This review will summarize these gene therapy strategies aimed at
      increasing the survival of patients with leukemia.

PMID- 9021742
TI  - Efficient removal of loxP-flanked DNA sequences in a gene-targeted locus by
      transient expression of Cre recombinase in fertilized eggs.
AB  - The bacteriophage P1 Cre/loxP site-specific recombination system is a useful tool
      for engineering chromosomal changes in animal cells. Transient expression of the
      Cre recombinase gene directly introduced into fertilized eggs by pronuclear
      injection has been reported to provide an efficient method of transgene
      modulation in fertilized eggs. In the present study, we examined the efficacy of
      this method to remove loxP-flanked DNA sequences in a gene-targeted locus in
      fertilized eggs. We replaced a part of the T-cell receptor gamma (TCR V gamma)
      locus with homologous sequences containing a loxP-flanked neogene in mouse
      embryonic stem (ES) cells by gene-targeting technique. The resulting ES cell
      clones containing the mutant allele (V gamma LNL) were used to generate chimeric
      mice by blastocyst injection. Eight male chimeras were bred with superovulated
      wild-type female mice. One hundred and seventy-six fertilized eggs were
      collected, and subjected to pronuclear injection of the Cre expression plasmid,
      pCAGGS-Cre, of a covalently closed circular form. Three out of 11 pups inherited
      the targeted V gamma locus. The inherited targeted allele of these 3 mice was
      shown to have undergone Cre-mediated recombination, resulting in a deletion of
      the loxP-flanked sequences (V gamma delta) as shown by Southern blot analysis of
      DNA from tail biopsies. All 3 founder mutant mice were capable of transmitting
      the V gamma delta locus to their offspring. The other 8 pups carried only wild
      type alleles. There were no pups carrying the unrecombined V gamma LNL locus.
      Thus, the frequency of Cre-mediated recombination was 100% (3/3) with this
      method. In contrast, when closed circular pCAGGS-Cre plasmid was introduced into
      ES cells by electroporation, the recombination frequency of the V gamma LNL locus
      was 9.6%. These results indicated that our system based on transient expression
      of the Cre recombinase gene directly introduced into fertilized eggs by
      pronuclear injection provides a fast and efficient method for generating mutant
      mice with desired deletions or translocations in target genes.

PMID- 9021743
TI  - Ouabain sensitivity and expression of Na/K-ATPase alpha- and beta-subunit isoform
      genes during bovine early development.
AB  - The fluid movements that arise during blastocyst formation (cavitation) are, at
      least in part, driven by the Na/K-ATPase. In this study, the reverse
      transcriptase-polymerase chain reaction (RT-PCR) was used to survey bovine pre
      attachment embryos for transcripts encoding known isoforms of the Na/K-ATPase
      alpha- and beta-subunits, including isoforms not previously detected during the
      first week of mammalian development. Transcripts encoding the Na-K-ATPase alpha
      1, alpha 2, alpha 3 and beta 2 isoforms were detected throughout bovine
      preattachment development. This is the first indication that alpha 2, alpha 3 and
      beta 2 mRNAs are expressed during this early developmental interval. As in the
      mouse, beta 1-subunit transcripts were not detected until the morula stage and
      were also present in blastocysts. Thus, in two mammalian species an increase in
      abundance of beta 1 isoform transcripts in the morula stage is coincident with
      the onset of cavitation. Transcripts encoding the recently characterized alpha 4
      isoform were not detected. The sensitivity of bovine blastocysts to ouabain (a
      potent inhibitor of Na/K-ATPase) was determined by assessing the ability of
      bovine blastocysts to recover in ouabain supplemental culture medium following
      cytochalasin-induced blastocyst collapse. Re-expansion of bovine blastocysts was
      inhibited in all ouabain concentrations down to 10(-9) M. Mouse blastocysts, in
      contrast, were sensitive to ouabain at or above 10(-3)M. These results have
      established that transcripts encoding multiple isoforms of both the alpha and
      beta subunits of the Na/K-ATPase are expressed throughout early bovine
      development and that bovine blastocysts display a greater sensitivity to ouabain
      than murine blastocysts. Future analysis will determine the possible individual
      and collective roles of these isoforms during blastocyst formation.

PMID- 9021744
TI  - Expression of c-fos and jun protooncogenes in ovine trophoblasts in relation to
      interferon-tau expression and early implantation process.
AB  - Expression of c-fos and jun protooncogenes was analyzed in the ovine
      extraembryonic trophoblast from days 14-18 of gestation, using Northern and
      Western blotting and immunohistochemistry. This study was carried out in relation
      to the early implantation process and the expression of interferon-tau, which is
      secreted in large amounts for a few days before implantation. Our results
      demonstrated that c-fos, c-jun, and junB were differently expressed in the ovine
      trophoblast around the time of implantation. The c-fos mRNA and protein were
      detected at high levels prior to attachment and decreased thereafter, following
      the pattern of expression of interferon-tau, whereas c-jun expression was
      maintained at relatively high levels during the implantation process. By
      contrast, the levels of junB mRNA and protein decreased prior to attachment.
      Immunohistochemical studies indicated that JunB, like C-Fos and interferon-tau,
      was no longer expressed in the trophoblastic cells which had established cellular
      contacts with the uterine epithelium. A striking finding in this study is the
      temporal correlation between the accumulation of c-Fos and c-Jun proteins and the
      expression of the interferon-tau (days 14 and 15 of gestation). We also showed by
      gel-retardation assays that an AP-1-like site present in the promoter of one
      interferon-tau gene was functional in vitro, as judged by its ability to bind day
      15 trophoblast nuclear protein extracts. Nuclear proteins binding to this site
      had the characteristics of AP-1, as judged by the ability to be competed
      efficiently by a consensus TRE (12.0-tetradecanoyl phorbol 13-acetate-responsive
      element)-site oligonucleotide and by antibodies to c-Fos and Jun proteins. These
      results suggest that Fos and Jun could form regulatory complexes of interferon
      tau expression and/or are regulated by common mechanisms which are still unknown.

PMID- 9021745
TI  - Differential responses of bovine oocytes and preimplantation embryos to heat
      shock.
AB  - The authors sought to determine whether developmental differences in the
      magnitude of embryonic mortality caused by heat stress in vivo are caused by
      changes in resistance of embryos to elevated temperature. In this regard,
      responses of oocytes, two-cell embryos, four-to eight-cell embryos, and compacted
      morulae to heat shock were compared. An additional goal was to define further the
      role of cumulus cells and glutathione in thermoprotection of oocytes. In
      experiment 1, heat shock (41 degrees C for 12 hr) decreased the number of embryos
      developing to the blastocyst stage for two-cell (26% vs. 0%) and four- to eight
      cell (25% vs. 10%) embryos but did not affect morulae (37% vs. 42%). In
      experiment 2, exposure of two-cell embryos to 41 degrees C for 12 hr reduced the
      number of four- to eight-cell embryos present 24 hr after the end of heat shock
      (88% vs. 62%). In experiment 3, heat shock reduced the number of two-cell embryos
      developing to blastocyst (49% vs. 8%) but did not affect subsequent development
      of oocytes when heat shock occurred during the first 12 hr of maturation (46% vs.
      41% development to blastocyst); membrane integrity was not altered. In experiment
      4, oocytes were cultured with an inhibitor of glutathione synthesis, DL
      buthionine-[S,R]-sulfoximine (BSO), for 24 hr and exposed to 41 degrees C for the
      first 12 hr of maturation. Percentages of blastocysts were 35% (39 degrees C),
      18% (41 degrees C), 17% (39 degrees C + BSO), and 11% (41 degrees C + BSO). For
      experiment 5, oocytes were either denuded or left with cumulus intact and were
      then radiolabeled with [35S]methionine and [35S]cysteine at 39 degrees C or 41
      degrees C for 12 hr. Exposure of oocytes to 41 degrees C for 12 hr reduced
      overall synthesis of 35S-labeled TCA-precipitable intracellular proteins (18,160
      vs. 14,594 dpm/oocyte), whereas presence of cumulus increased synthesis (9,509
      vs. 23,246). Analysis by two-dimensional SDS PAGE and fluorography revealed that
      heat shock protein 68 (HSP68) and two other putative heat shock proteins, P71 and
      P70, were synthesized by all oocytes regardless of treatment. Heat shock did not
      alter the synthesis of HSP68 or P71 but decreased amounts of newly synthesized
      P70. Cumulus cells increased synthesis of P71 and P70. Results indicate there is
      a biphasic change in resistance to elevations in temperature as oocytes mature,
      become fertilized, and develop. Resistance declines from the oocyte to the two
      cell stage and then increases. Evidence suggests a role for cumulus cells in
      increasing HSP70 molecules and protein synthesis. Data also indicate a role for
      glutathione in oocyte function.

PMID- 9021746
TI  - Modifications made to culture medium by bovine oviduct epithelial cells: changes
      to carbohydrates stimulate bovine embryo development.
AB  - Co-culture remains a common method to support the development of bovine embryos,
      derived from IVM/IVF procedures. However, the mechanism by which somatic cells
      confer their benefit to the developing embryo remains undetermined. This study
      therefore analysed the changes made to the culture medium TCM-199, used in bovine
      embryo co-culture systems, by somatic cells and determined the effects of
      specific changes in medium composition on bovine embryo development in culture.
      Bovine oviduct epithelial (BOE), Buffalo rat liver (BRL) and fibroblast (3T3)
      cells were compared. The concentrations of glucose, L-lactate, pyruvate, amino
      acids, NH4+, H+ and the gas tensions of O2 and CO2 were measured in TCM-199
      supplemented with 10% fetal calf serum (FCS) prior to and directly following 48 h
      incubation periods with each cell type. All three somatic cell types modified the
      carbohydrate composition of the media in a similar manner with the greatest
      changes made by the BOE cells. Notable alterations were an increase in the levels
      of L-lactate and pyruvate and a reduction in glucose concentration, which in the
      case of the BOE cells, fell from 5.55 mM to 2.67 mM. In order to determine the
      relevance of such changes in carbohydrate concentrations on bovine embryo
      development, modifications were made to carbohydrate levels in synthetic oviduct
      fluid (SOF) medium and their effect on blastocyst development in vitro assessed.
      In SOF medium supplemented with amino acids and BSA (SOFaa), significantly more
      zygotes developed to the blastocyst stage (64%; P < 0.01) than in SOFaa medium
      with the concentrations of glucose, D/L-lactate and pyruvate equivalent to those
      in TCM-199 (11%). Interestingly, when the levels of carbohydrates in SOFaa
      mimicked those present in TCM-199 following a 48 h incubation with BOE cells, 57%
      of zygotes reached the blastocyst stage. This improvement was ascribed to the
      reduction in glucose and increases in D/L-lactate and pyruvate concentrations in
      the culture system. Results from this study demonstrate that BOE cells create an
      environment favourable to embryonic development. The analysis of media samples by
      enzymatic methods meant that only the biologically active L-isomer of lactate was
      quantified. However, in SOFaa, both the L-isomer and inactive D-isomer are
      present in equimolar amounts. As such, culture media in which D/L-lactate syrup
      is used actually contain only 50% biologically active lactate meaning that all
      D/L-lactate concentrations are reported at twice the effective concentration.
      Therefore the effect of D/L-lactate concentration on blastocyst development was
      subsequently determined in this study. Blastocyst development was poor (24-36%)
      until the total D/L-lactate was present in the culture system at concentrations
      equal to or greater than 0.82 mM. However, blastocyst cell numbers remained low
      (60.1 +/- 6.9 - 78.5 +/- 6.6) until a total D/L-lactate concentration of 3.3 mM.
      This data reinforces that embryo morphological appearance is not sensitive enough
      to be used as the sole criterion for assessing embryo development.

PMID- 9021747
TI  - Involvement of purine nucleotide synthetic pathways in gonadotropin-induced
      meiotic maturation in mouse cumulus cell-enclosed oocytes.
AB  - This study was carried out to test the hypothesis that purine nucleotide
      generating pathways are required for ligand-stimulated oocyte maturation in
      meiotically arrested cumulus cell-enclosed oocytes. Oocytes from hormonally
      primed, immature mice were cultured overnight in Eagle's minimum essential medium
      containing dibutyryl cyclic AMP (dbcAMP) (to maintain meiotic arrest), plus
      either mycophenolic acid or alanosine (inhibitors of guanyl and adenyl nucleotide
      production, respectively). Follicle-stimulating hormone (FSH) was added either at
      the outset of culture or after a 3-hr preincubation period. Under either of these
      conditions, the inhibitors suppressed FSH induction of germinal vesicle breakdown
      (GVB). In addition, the potency of FSH as an inducer of GVB was reduced following
      the 3-hr preincubation period, but this could be prevented if nucleotide
      precursors such as hypoxanthine, guanosine, or adenosine were included during the
      first 3 hr. Furthermore, preincubation had little effect on FSH induction of GVB
      when hypoxanthine was used to maintain meiotic arrest for the entire culture
      period. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, could not
      mimic this protective effect of hypoxanthine. Azaserine and aminopterin,
      inhibitors of purine de novo synthesis, blocked hormone-triggered maturation in
      dbcAMP-arrested oocytes, but had little effect on hypoxanthine-arrested oocytes.
      The effect of azaserine on dbcAMP-treated oocytes could be reversed by the
      inclusion of AICA riboside, a compound that can be taken up by cells and
      phosphorylated to form AICAR, which can enter the purine de novo pathway at a
      point distal to the sites of azaserine inhibition. FSH was stimulatory to purine
      de novo synthesis, while azaserine, aminopterin, hypoxanthine, and AICA riboside
      all suppressed de novo synthesis in the presence or absence of FSH, with dbcAMP
      having no effect. HPLC analysis of 14C-hypoxanthine metabolism in oocyte-cumulus
      cell complexes revealed that changes in the pattern of purine metabolism did not
      mediate the meiosis-inducing effect of FSH. These data support the conclusion
      that purine nucleotide-generating pathways are vital participants in the
      mechanism(s) regulating hormone-induced meiotic maturation, and that either the
      de novo or salvage pathway can fulfill this nucleotide requirement.

PMID- 9021748
TI  - Binding of boar spermatozoa to porcine oocytes: effect of low molecular weight 17
      kDa protein.
AB  - The effect of seminal plasma and low molecular weight ACR.3 (17 kDa) protein on
      boar spermatozoa-porcine oocyte binding was examined. Boar seminal plasma that
      contains the sperm-adhesive ACR.3 protein was added to spermatozoa prior to their
      coincubation with oocytes, and the binding capacity of the spermatozoa so treated
      was compared to that of untreated cells. Similarly, purified ACR.3 protein, that
      binds to the egg zona pellucida, was added to noncapacitated spermatozoa, and the
      binding capacity of treated and untreated cells was again evaluated. In the two
      cases, the treatment of spermatozoa reduced their capacity to bind to the zona
      pellucida. We propose that the reduction in binding is due to competition for the
      ACR.3 binding sites on the zona pellucida between the soluble ACR.3 protein and
      the ACR.3 protein attached to the sperm surface. Furthermore, sperm-ZP binding
      was examined in the presence of ACR.3 monoclonal antibody, which specifically
      reacts with ACR.3 protein. Preliminary results show that addition of ACR.3
      monoclonal antibody to a suspension of boar spermatozoa prior to their
      coincubation with oocytes did not markedly change sperm-zona binding in
      comparison with the control untreated spermatozoa. Our results suggest that ACR.3
      protein may mediate the primary sperm-egg zona pellucida binding, and that it is
      one of the likely candidates for the primary sperm-ZP binding protein.

PMID- 9021749
TI  - Injection of a porcine sperm factor triggers calcium oscillations in mouse
      oocytes and bovine eggs.
AB  - Fertilization in mammals is associated with the generation of intracellular
      calcium ([Ca2+]i) oscillations. The site of, or mechanism(s) utilized by, the
      sperm to initiate and maintain these Ca2+ responses is not known. In this study,
      we tested the hypothesis that a factor from the sperm is capable, upon release
      into the oocyte's cytosol, of initiating oscillations. A sperm factor, prepared
      from porcine semen, was injected into mouse oocytes and bovine eggs that had been
      loaded with fura-2 dextran, a fluorescent Ca2+ indicator. The resulting Ca2+
      responses were monitored and compared to those characteristic of each species.
      Our results show that injection of sperm factor triggered long-lasting [Ca2+]i
      oscillations, and that the observed patterns were species-specific. In mouse
      oocytes, sperm factor-induced [Ca2+]i rises exhibited high frequency, whereas in
      bovine eggs, Ca2+ responses were separated by long intervals. Further
      characterization of the sperm factor revealed that it was predominantly present
      in sperm preparations, that it contained a protein moiety, and that it was
      unlikely to be a protease. The intracellular Ca2+ channels/receptors through
      which the sperm factor-mediated Ca2+ release was investigated by using heparin, a
      competitive inhibitor of the inositol 1,4,5 trisphosphate receptor (InsP3R), and
      ryanodine, which binds the ryanodine receptor (RyR). The sperm factor appeared to
      stimulate InsP3R, at least in mouse oocytes, because sperm factor-induced
      oscillations were delayed or blocked in all oocytes by injection of heparin. RyR
      may be involved in the modulation of these oscillations, since addition of
      ryanodine modified Ca2+ responses to the sperm factor. The present results
      support the hypothesis that a factor from the sperm is involved in the generation
      of fertilization-associated [Ca2+]i oscillations.

PMID- 9021750
TI  - Follicle-oocyte atresia and temporal taphonomy in cold-stored domestic cat
      ovaries.
AB  - In vitro oocyte maturation followed by in vitro fertilization (IVM/IVF) success
      in the domestic cat remains inferior to commonly studied livestock or laboratory
      species. The objectives here were (1) to histologically assess atresia status of
      freshly excised follicle/oocyte complexes, and (2) to evaluate taphonomic change
      (deterioration after excision) of these complexes after ovarian cold storage for
      up to 48 h. After excision of 50 ovarian pairs, one ovary was preserved
      immediately and the other stored in phosphate buffered saline (4 degrees C) for
      4, 8, 12, 24, or 48 h before fixation and examination. Ovaries were classified as
      luteal if prominent corpora lutea (CL) were present or as follicular if antral
      follicles and no CL were present. Two classes of follicle-oocyte complexes
      (preantral and antral) were microscopically evaluated. Of the 2,280 complexes
      examined, 64.3% demonstrated clear evidence of slight to severe degeneration,
      with various stages being described and photographed for the first time. There
      was no histological evidence indicating distinctive morphological differences
      between oocytes recovered from follicular versus luteal donors. Storage of whole
      ovaries in cold saline inhibited taphonomic changes for 48 h after excision. In
      summary, there is marked variability in the number and quality of follicle
      populations in cat ovaries. A high percentage of full-sized follicular oocytes
      are undergoing atresia at any given time. However, additional gross degeneration
      as a result of cold-storage appears modest for up to 48 h. Nonetheless, this high
      level of natural atresia in the cat likely contributes to comparatively lower
      IVM/IVF success than in other species.

PMID- 9021751
TI  - Species-specific effect of oviductal glycoproteins on hamster sperm binding to
      hamster oocytes.
AB  - The secretory cells of the oviductal epithelium secrete a high-molecular-weight
      glycoprotein (OGP). OGPs from different mammalian species show similar
      immunological characteristics, their cDNAs show high homologies, and they
      associate with the zona pellucida of oviductal oocytes in vivo. The purpose of
      this study was to determine the effect of OGP obtained from different species on
      the binding of hamster sperm to hamster oocytes. Hamster oocytes were inseminated
      (30 min) in the presence or absence of homologous or heterologous OGPs, and sperm
      bound/oocyte were counted after removing loosely attached sperm. Ovarian oocytes
      had an average of 2.9 +/- 0.6 sperm bound/oocyte, whereas oviductal oocytes had
      36.3 +/- 2.7. Hamster OGP (0.1 mg/ml) significantly increased sperm binding to
      ovarian oocytes twofold and had no effect on sperm bound/oviductal oocytes. Human
      OGP (0.5 mg/ml) significantly decreased sperm binding to ovarian oocytes (0.9 +/-
      0.3 sperm bound/oocyte). This effect was dose dependent for oviductal oocytes and
      could be blocked by preincubating human OGP with a specific antibody to human
      OGP. The presence of baboon and cow OGP during the insemination of hamster
      oviductal oocytes also resulted in a significant decrease in sperm bound/oocyte,
      whereas the addition of hamster OGP to hamster oviductal oocytes had no effect.
      These results show that homologous OGP enhances sperm binding to the ZP, whereas
      heterologous OGP inhibits that effect. Thus, our results suggest that OGP plays a
      role in the species-specific characteristics of sperm/ZP interaction, and that
      one must use a homologous system (OGP and gametes from the same species) to study
      the biological effect of OGP.

PMID- 9021752
TI  - Nucleus ultrastructure and transcriptional activity of bovine oocytes in
      preantral and early antral follicles.
AB  - An understanding of the recruitment and growth of follicles within the bovine
      ovary is crucial to their successful exploitation in vitro. The aim of the
      present study was to describe the nuclear ultrastructure and transcriptional
      activity of primordial to early tertiary follicular oocytes from bovine adult
      ovaries. Small blocks of ovarian cortex were incubated in medium enriched with 3H
      uridine for 30 min. Subsequently, the tissue blocks were fixed in Karnowsky's
      fixative, dehydrated, epon embedded, sectioned (2 microns), processed for
      autoradiography, and examined under light microscopy. Sections showing preantral
      follicles with presumptive oocyte nucleoli were reembedded for transmission
      electron microscopy. The follicles were divided into five categories: 1) resting
      primordial, with a single layer of flattened granulosa cells, 2) activated
      primordial, with a single layer of flattened and some cuboidal granulosa cells,
      3) primary, with a single layer of cuboidal granulosa cells, 4) secondary, with a
      complete or incomplete bilayer of cuboidal cells, and 5) tertiary, with more than
      two layers of granulosa cells delineating one or more intercellular cavities. The
      granulosa cells of all follicle classes were transcriptionally active. However,
      the oocytes did not display transcriptional activity, as measured by the present
      means, until the secondary and tertiary follicular stages. The oocyte nucleolus
      was granular in the primordial follicles. Following follicular activation,
      fibrillar centres invaded the nucleolus and, in the early tertiary follicle,
      numerous fibrillar centres were distributed throughout the nucleolus. In
      conclusion, the oocyte nucleolar function is gradually activated at follicle
      activation, and oocyte transcription is initiated at approximately the time of
      the secondary follicle stage.

PMID- 9021753
TI  - Study of protein kinase C antagonists on cortical granule exocytosis and cell
      cycle resumption in fertilized mouse eggs.
AB  - Although pharmacological agonists of protein kinase C (PKC) stimulate some events
      of mammalian egg activation, including cortical granule (CG) exocytosis, it is
      not known if these events are dependent on PKC activation during the normal
      process of fertilization. In order to examine the potential role of PKC in CG
      exocytosis, this study investigated whether PKC agonists faithfully mimic CG
      release and whether PKC antagonists block fertilization-induced CG release in
      mature mouse eggs. Phorbol ester (TPA, 2.5 ng/ml) treatment resulted in an
      atypical pattern of CG release in which there was a greater net loss of CGs in
      the equatorial region of the egg than in the region opposite the spindle. This
      pattern also was in contrast to that during fertilization, in which CG release
      occurred randomly throughout the cortex. Fertilization experiments utilized two
      different PKC inhibitors, bisindolylmaleimide (5 microM) and chelerytherine (0.8
      microM), targeted to both the "conserved" substrate and ATP binding domains of
      PKC. Simultaneous use of both inhibitors at maximal concentrations (compatible
      with fertilization and above their IC50S) resulted in no detectable inhibition of
      CG release in treated fertilized eggs compared to controls. In addition no
      inhibition of anaphase onset was observed in treated fertilized eggs. Activity of
      the inhibitors was verified by demonstrating that they blocked the induction of
      CG loss by TPA. Moreover, 1 microM staurosporine, a potent but less specific
      antagonist of PKC, also did not block CG loss whereas the metaphase-anaphase
      transition was temporarily inhibited. The results indicate that TPA does not
      faithfully mimic CG release in fertilized eggs, that a role for PKC in CG release
      at fertilization remains to be established, and that other calcium-dependent
      effectors may be involved in CG exocytosis.

PMID- 9021754
TI  - Inhibition of rat brain protein kinase C by lipid soluble psychotropics.
AB  - Lipid soluble psychotropics inhibit brain PKC-catalyzed phosphorylation of
      exogenous and endogenous proteins to varying degrees. These drugs were better
      inhibitors of Ca2+/PL-dependent phosphorylation of histones (H) than that of
      Ca2+/PL-independent protamine sulfate (PrSO4): antidepressants/antipsychotics
      displayed IC50 of 0.1 to 0.16 mM towards H and 0.3 to 4.0 mM towards PrSO4
      phosphorylation. Sedatives/anesthetics were less efficient inhibitors with much
      higher IC50 of 1.3 to 40 mM. Phosphorylation of a Ca(2+)-dependent but PL
      independent p80 protein and of a cluster of Ca2+/PL-dependent proteins, p16-20,
      in brain was also inhibited by the antidepressants/antipsychotics but not by the
      sedatives/anesthetics. Phorbol ester binding studies revealed that these
      inhibitors do not compete for DAG binding site(s) on PKC. However, both drug-PL
      and drug-PKC interactions seem to be relevant in their mechanism of action.
      Furthermore, our data suggest that the hydrophobic nature of the propanamine side
      chain or its N-methylated version as well as the tricyclic nucleus influence drug
      PKC interaction. Although many of these drugs have other accepted modes of
      action, modulation of PKC activity in brain, may be yet another aspect to be
      considered in their mechanism of action.

PMID- 9021755
TI  - Serotonin synthesis increased in terminals four days after reserpine treatment:
      an autoradiographic study in rat brain.
AB  - The rate of 5-HT synthesis was determined in discrete rat brain regions 4 days
      after a single dose of reserpine (10 mg/kg) or reserpine carrier (controls),
      using an autoradiographic method with labelled alpha-methyl-L-tryptophan as a
      tracer. The results show that the rate of 5-HT synthesis was unchanged in the
      dorsal and median raphe, significantly decreased in the raphe magnus, and
      significantly increased in areas rich in serotonergic nerve terminals (i.e.,
      hypothalamus, hippocampus, median geniculate body, parietal and visual cortices).
      An increase in tryptophan hydroxylase activity could account for the increase in
      the rate of serotonin synthesis seen in some regions. Since the 5-HT synthesis
      rate showed regional variability there seems to be a need for regional studies of
      the effect of drugs on the 5-HT synthesis. In addition, the 5-HT synthesis rate
      was not significantly different from that in controls in many of the brain
      regions.

PMID- 9021757
TI  - Amino acid metabolism in rat hippocampus during the period of brain growth spurt.
AB  - We studied protein synthesis, lipid synthesis and CO2 production by oxidation of
      glycine, alanine and leucine by slices of rat hippocampus during the period of
      brain growth spurt. The metabolism of the three amino acids decreased with the
      age of the animals. A major reduction was observed in protein synthesis, which
      was 4 times higher at 7 days of age than at 21 days of age for all amino acids
      studied. Glycine oxidation to CO2 was twice as high as alanine oxidation and ten
      times higher than leucine oxidation. The major pathway of leucine utilization was
      incorporation into proteins. Glycine was the amino acid that had the highest
      metabolic rate.

PMID- 9021756
TI  - Metallothionein inducers protect against 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine neurotoxicity in mice.
AB  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces
      parkinsonism in human and non-human primates. Free radicals are thought to be
      involved in its mechanism of action. Recently, the participation of
      metallothionein as scavenger of free radicals has been proposed. In this work, we
      studied the effect of metallothionein inducers in MPTP neurotoxic action. Male
      swiss albino mice were pretreated either with cadmium (1 mg/kg) or dexamethasone
      (5 mg/kg), two well-known inducers of metallothionein synthesis, and 5 hours
      later with an MPTP administration (30 mg/kg). Treatment schedule was repeated
      daily for either 3 or 5 consecutive days. All animals were killed 7 days after
      the last administration, and striatal dopamine and homovanillic acid contents
      were analyzed as an end-point of MPTP neurotoxicity. Striatal dopamine content of
      cadmium plus MPTP-treated animals (3-days) increased by 32%, and 48% (5-days) vs
      MPTP-alone animals. Dexamethasone plus MPTP-treated group also showed increased
      dopamine levels 28% (3-days) and 43% (5-days). MPTP treatment reduced striatal
      metallothionein concentration (49% vs control animals). Dexamethasone and cadmium
      increased metallothionein concentrations in MPTP-treated groups, by 77% and 82%
      respectively. Results suggest that metallothionein induction provide a
      significant resistance factor against the deleterious effect of MPTP.

PMID- 9021758
TI  - Different administration schedules of the same dose of 2,5-hexanedione influence
      the development of neuropathy and the toxicokinetics.
AB  - The same total dose (1.2 g/kg/week) of 2,5-hexanedione (2,5-HD) was administered
      subcutaneously at 100 mg/kg/12 hr, 200 mg/kg/24 hr, and 400 mg/kg/48 hr to three
      groups of Donryu rats. The peripheral neuropathy induced by 2,5-HD was confirmed
      by clinical observation every day, and neurophysiological measurements every 4
      weeks. During the 15th week of this experiment, 2,5-HD concentrations in plasma
      0.5 to 24 hours after injection were determined. It was found that the greater
      the dose of 2,5-HD per treatment injected, the earlier peripheral neuropathy
      developed. Toxicokinetic analysis showed that both the values of the area under
      the plasma concentration versus time curve and the half life of 2,5-HD were
      increased, but the excretion parameters (Ke) were decreased, in animals treated
      with 200 mg/kg/24 hr and 400 mg/kg/48 hr 2,5-HD.

PMID- 9021759
TI  - Chronic administration of Oren-gedoku-to (TJ15) inhibits ischemia-induced changes
      in brain indoleamine metabolism and muscarinic receptor binding in the Mongolian
      gerbil.
AB  - We examined the effect of Oren-gedoku-to (TJ15), which is a traditional herbal
      Kampo prescription used as an anti-cerebral apoplexy agent on these changes.
      Chronic pre- and post-ischemia TJ15 oral administration almost completely
      abolished the ischemia-induced muscarinic receptor reduction and 5
      hydroxyindoleacetic acid level increase. These results suggest that TJ15 prevents
      cholinergic synaptic dysfunction and serotonergic presynaptic hyperactivity
      induced by transient ischemia.

PMID- 9021760
TI  - Age-related ischemia in the brain following bilateral carotid artery occlusion-
      collateral blood flow and brain metabolism.
AB  - Cerebral blood flow (CBF) and cerebellar blood flow (CeBF) were measured and
      correlated with brain lactate, pyruvate and adenosine triphosphate concentrations
      from groups representing 3-week old suckling (n = 10), 18-22-week old adult (n =
      9) and 70-week old aged (n = 7) Sprague-Dawley rats before and during bilateral
      carotid occlusion (BCO). The steal ratio, calculated as the ratio of %control CBF
      to %control CeBF, was 1.02 +/- 0.06 (mean +/- SEM) at 60 minutes of BCO in adult
      rats that exhibited normal levels of brain metabolites. By contrast, the ratios
      significantly decreased to 0.74 +/- 0.06 in suckling rats and 0.69 +/- 0.06 in
      aged rats with simultaneous increases by 2.4 to 2.9-fold of tissue lactate.
      Pyruvate and lactate/pyruvate ratio also increased by 1.4 to 1.8 times control in
      both suckling and aged rats. We conclude that there is age-related steal
      phenomenon occurring with blood flow during BCO. Ischemic derangement of the
      brain metabolism is in part related to poor blood supply from the posterior
      circulation in suckling and aged rats.

PMID- 9021761
TI  - Morphological and biochemical changes during programmed cell death of rat
      cerebellar granule cells.
AB  - Cultured cerebellar granule cells deprived of depolarizing concentrations of KCl
      and serum die by programmed cell death. Recently, it was shown that serum removal
      by itself can lead to oxidative stress and DNA fragmentation in these cells. We
      have modified the protocol which initiates cell death in such a way that only the
      effect of KCl withdrawal-induced cell death was observed. We have performed a
      series of experiments to correlate the structural and biochemical changes in this
      process of cell death. Significant morphological alterations occur in cell bodies
      and neurites during a 48-hour period of KCl removal. Cell viability dropped to
      53%, 34% or 10% of control levels, respectively, as a result of 1-, 2-, or 3-day
      KCl removal. A series of experiments was conducted to determine the change of
      total protein level, protein synthesis rate, RNA synthesis rate, and
      mitochondrial activity during the first 48 hours of KCl removal. These studies
      not only provide a picture correlating the morphological and biochemical changes
      in the process of programmed cell death, but also serve as a reference for future
      studies of this complex phenomenon.

PMID- 9021763
TI  - Non-muscarinic- and non-adrenergic-mediated effects of lindane on
      phosphoinositide hydrolysis in rat brain cortex slices.
AB  - The influence of lindane upon phosphatidylinositol hydrolysis in rat brain cortex
      slices has been investigated using anion-exchange chromatography in order to
      separate the water-soluble inositol metabolites. Acetylcholine, noradrenaline,
      and lindane induce the accumulation of myo-[2-3H]inositol as the water-soluble
      inositol metabolites. However, the cholinergic muscarinic antagonist atropine
      inhibited the stimulatory response of carbachol, but practically unmodified the
      effect that lindane has on inositol phosphate production. Also, prazosin anti
      alpha 1 adrenoreceptors blocked noradrenaline-induced phosphoinositide
      hydrolysis, but had no effect on lindane-induced increase of inositol phosphate
      levels. The results suggest that lindane does not exert a general effect on the
      receptor-stimulated formation of inositol phosphates by both muscarinic and alpha
      1-adrenergic agonists.

PMID- 9021762
TI  - Degradation of Alzheimer's beta-amyloid protein by human and rat brain
      peptidases: involvement of insulin-degrading enzyme.
AB  - We examined the degradation of Alzheimer's beta-amyloid protein (1-40) by soluble
      and synaptic membrane fractions from post mortem human and fresh rat brain using
      HPLC. Most of the activity at neutral pH was in the soluble fraction. The
      activity was thiol and metal dependent, with a similar inhibition profile to
      insulin-degrading enzyme. Immunoprecipitation of insulin-degrading enzyme from
      the human soluble fraction using a monoclonal antibody removed over 85% of the
      beta-amyloid protein degrading activity. Thus insulin-degrading enzyme is the
      main soluble beta-amyloid degrading enzyme at neutral pH in human brain. The
      highest beta-amyloid protein degrading activity in the soluble fractions occurred
      between pH 4-5, and this activity was inhibited by pepstatin, implicating an
      aspartyl protease. Synaptic membranes had much lower beta-amyloid protein
      degrading activity than the soluble fraction. EDTA (2mM) caused over 85%
      inhibition of the degrading activity but inhibitors of endopeptidases -24.11, 
      24.15, -24.16, angiotensin converting enzyme, aminopeptidases, and
      carboxypeptidases had little or no effect.

PMID- 9021764
TI  - Brain monoamine changes in rats after short periods of ozone exposure.
AB  - We have shown in our laboratory that cat's and rat's sleep disturbances are
      produced by 24 h of ozone (O3) exposure, indicating that the central nervous
      system is affected by this gas. To demonstrate the probable changes in brain
      neurotransmitters, we evaluated the monoamine contents of the midbrain and
      striatum of rats exposed to 1 part per million O3 for 1 or 3 hours periods. The
      results were compared with rats exposed to fresh air and to those exposed to 3
      hours of O3 followed by 1 or 3 hours of fresh air. We found a significant
      increase in dopamine (DA) and its metabolites noradrenaline (NA) and 3,4
      dihydroxyphenylacetic acid (DOPAC), as well as an increase in the 5
      hydroxyindolacetic acid (5-HIAA) contents of the striatum. There were no changes
      in homovanillic acid (HVA) and serotonin (5-HT) levels during O3 exposure.
      Additionally, an increase in DA, NA and 5-HIAA in the midbrain during O3 exposure
      was observed. Turnover analysis revealed that DA increased more than its
      metabolites in both the midbrain and striatum. However, the metabolite of 5-HT,
      i.e. 5-HIAA, increased more than its precursor, this reaching statistical
      significance only in the midbrain. These findings demonstrate that O3 or its
      reaction products affect the metabolism of major neurotransmitter systems as
      rapidly as after 1 h of exposition.

PMID- 9021765
TI  - In vitro effects of arachidonic and L-glutamic acids on the high-affinity choline
      transport in rat hippocampus.
AB  - A second messenger role for arachidonic acid (AA) in the regulation of the high
      affinity choline uptake (HACU) was suggested. It was reported that micromolar
      concentrations of AA applied in vitro decreased the HACU values and increased the
      specific binding of [3H]hemicholinium-3 ([3H]HCh-3). It was published that L
      glutamic acid (GA) applied in vivo produced a fall in the HACU values. In
      addition, GA liberates free AA. In this study, an ability of GA to influence in
      vitro the activity of presynaptic cholinergic nerve terminals via its effect on
      the release of AA is investigated in hippocampal synaptosomes of young Wistar
      rats. Millimolar concentrations of GA decrease both the high- and low-affinity
      choline uptake, the specific as well as nonspecific binding of [3H]HCh-3 and the
      activity of Na+, K(+)-ATPase. Kinetic analysis (Lineweaver-Burk and Scatchard
      plots) reveals a change in Vmax and Bmax, but not in KM and KD. It appears very
      likely that under normal conditions GA applied in vitro is not able to change
      markedly the choline transport via its effect on the release of AA. Results
      confirm the hypothesis about an indirect inhibitory role for glutamatergic
      receptors on cholinergic cells.

PMID- 9021766
TI  - Reduction in thermal hyperalgesia by intrathecal administration of glycine and
      related compounds.
AB  - We have previously shown in animal models that enhanced segmental glycine release
      is produced by neuroaugmentation techniques commonly used to control pain in
      humans. Our current hypothesis is that glycine administered intrathecally reduces
      the pain response evoked by the hotplate analgesia meter method. Neuropathic rats
      created by unilateral partial ligation of the sciatic nerve were treated with
      intrathecal infusion of glycine, strychnine, MK-801, or 5-7 DKA at 0.1 mumol for
      2 hours at a rate of 10 microliters/min. Time required for limb withdrawal at 42
      degrees C was significantly increased after glycine administration but not
      altered by strychnine, a specific glycine receptor antagonist. Administration of
      the NMDA receptor antagonist, MK-801, blocked the influence of glycine, with a
      less obvious antagonistic response from 5.7 DKA. Our results provide evidence
      that glycine and related compounds significantly modify thermal hyperalgesia, and
      may operate primarily through the NMDA receptor complex.

PMID- 9021767
TI  - The inhibitory effects of N omega-nitro-L-arginine methyl ester on nitric oxide
      synthase activity vary among brain regions in vivo but not in vitro.
AB  - We studied the effects of intracerebroventricular and intraperitoneal injection
      and the in vitro effects of N omega-nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of nitric oxide synthase, on the nitric oxide synthase activities of
      the cerebellum, brainstem, hypothalamus, hippocampus, and the remainder of the
      brain after dissections. Male rats were chronically implanted with lateral icv
      guide cannula. L-NAME was injected in doses of 0.2, 1, and 5 mg
      intracerebroventricularly, and 50 mg/kg intraperitoneally. L-NAME induced dose
      dependent suppression of NOS activities in each brain region. The threshold dose
      was 0.2 mg; 1 mg L-NAME completely abolished brain nitric oxide synthase activity
      90 min after the injection. Brain NOS activities returned to baseline level 48 h
      after the injection of 5 mg L-NAME. There were significant differences between
      the sensitivity of various regions to L-NAME after in vivo but not in vitro
      administration of the enzyme inhibitor. These findings indicate that
      intracerebroventricular injection of L-NAME is a useful tool for inhibiting brain
      nitric oxide synthase activities in vivo. The differences between the sensitivity
      of different brain regions to L-NAME as well as the relative fast recovery of
      nitric oxide synthase activities must be taken into account when L-NAME is
      administered intracerebroventricularly to rats.

PMID- 9021768
TI  - Melatonin effects on serotonin synthesis and metabolism in the striatum, nucleus
      accumbens, and dorsal and median raphe nuclei of rats.
AB  - This work examined the influence of the pineal gland and its hormone melatonin on
      the metabolism of serotonin (5-HT) in discrete areas of the forebrain, such as
      the striatum and the nucleus accumbens, and the midbrain raphe. The content of 5
      HT and its major oxidative metabolite, the 5-hydroxyindoleacetic acid (5-HIAA),
      as well as the in-vivo tryptophan hydroxylation rate were examined after long
      term pinealectomy (one month) and daily melatonin treatment (500 micrograms/kg;
      twice daily for ten days) in pinealectomized rats. Pinealectomy did not alter 5
      HT content in any of these brain areas, but it significantly increased the
      content of 5-HIAA in striatum and the 5-HIAA/5-HT ratio in nucleus accumbens. The
      normal values of these parameters were recuperated after administration of
      exogenous melatonin, but it also increased the rate of tryptophan hydroxylation
      in both areas. In addition, melatonin treatment decreased the levels of 5-HIAA in
      dorsal raphe nucleus. These data suggest that the pineal gland, through the
      secretion of melatonin, modulates the local metabolism of 5-HT in forebrain areas
      by acting on the oxidative deamination. Moreover, melatonin injected in
      pinealectomized rats derives in a more extended effect than pinealectomy and
      induces a stimulation of 5-HT synthesis in the striatum, probably due to a
      pharmacological effect. These results point to the striatum as a target area for
      the interaction between pineal melatonin and the serotonergic function, and
      suggest a differential effect of the melatonin injected on areas containing
      serotonergic terminals and cell bodies, which may relevant for the mode of action
      of melatonin and its behavioral effects.

PMID- 9021786
TI  - Standardization of terminology of lower urinary tract function: pressure-flow
      studies of voiding, urethral resistance, and urethral obstruction. International
      Continence Society Subcommittee on Standardization of Terminology of Pressure
      Flow Studies.

PMID- 9021769
TI  - Ubiquitin-mediated stress response in a rat model of brain transient
      ischemia/hypoxia.
AB  - Ubiquitin (Ub) is a small 76-residue protein, involved in intracellular protein
      degradation through a specific ATP-dependent system, which uses Ub as a tag to
      label proteins committed to be hydrolyzed by a specific 26 S protease. PGP-9.5 is
      another important component of the Ub system, i.e. a neuron-specific carboxyl
      terminal hydrolase, which recycles Ub from Ub-polypeptide complexes. We have
      investigated the expression of Ub and PGP-9.5 in rat hippocampal neurons in an
      early phase of reperfusion in a model of transient global brain ischemia/hypoxia
      (bilateral occlusion of common carotid arteries for 10 min accompanied by mild
      hypoxia-15% O2-for 20 min), by means of immunohistochemical methods using light
      and electron microscopy. The intensity of Ub and PGP-9.5 immunoreactivity was
      evaluated by image analysis. We have detected a marked increase of Ub
      immunoreactivity (UIR) in neurons of CA1, CA2, CA3, CA4, and dentate gyrus
      subfields 1 hr after ischemia/hypoxia (but not after hypoxia only), statistically
      significant as confirmed by image analysis. Such increase in immunoreactivity in
      ischemic/hypoxic rats was localized essentially in the nuclei of hippocampal
      neurons. There were no changes in PGP-9.5 immunoreactivity. The data suggest that
      in the present model of rat brain ischemia/hypoxia Ub is involved in the neuronal
      stress response.

PMID- 9021787
TI  - Bladder compliance in patients with benign prostatic hyperplasia.
AB  - Factors influencing bladder compliance were examined in 116 patients with benign
      prostatic hyperplasia (BPH), by evaluating patients' histories, response of
      isolated bladder strips to acetylcholine, and the effect of prostatic urethral
      anesthesia. Patients' age, frequency of micturition, and duration of voiding
      difficulty were not correlated with bladder compliance. Bladder compliance was
      significantly low in patients within 30 days after urinary retention, as compared
      with bladder compliance in patients without an episode of retention. More than 30
      days after retention, however, there was a tendency toward increased bladder
      compliance. Restricted to patients without an episode of retention, bladder
      compliance in the overactive detrusor group was found to be significantly lower
      than in the normal group. The responses to acetylcholine of bladder strips were
      compared between patients with low and normal-compliance bladders. The dose
      response curve of patients with low-compliance bladders did not differ from that
      of those with normal compliance bladders, even when patients with an episode of
      retention were excluded. After prostatic urethral anesthesia, a significant
      increase of bladder compliance was observed in patients with an overactive
      detrusor, while the increase was not significant in patients with a normal
      detrusor. Our results strongly suggest that easy irritability of the anatomically
      altered prostatic urethra, as well as bladder over-distension caused by urinary
      retention, are important factors affecting bladder compliance in BPH patients.

PMID- 9021788
TI  - Can simultaneous perineal sonography and urethrocystometry help explain urethral
      pressure variations?
AB  - OBJECTIVE: To correlate urodynamic with perineal sonographic findings in pressure
      variations. PATIENTS AND METHODS: In 15 women presenting with urethral pressure
      variations a urodynamic evaluation with water filling cystometry, urethral
      pressure at rest and during coughing and uroflowmetry were performed. During
      water filling cystometry, there were simultaneous perineal video-sonography and
      urethrocystometry. Video ultrasound images and urodynamic curves were
      simultaneously monitored on a computer screen. RESULTS: Simultaneous ultrasound
      and urodynamic evaluation in the 15 patients revealed movements in two areas
      leading to urethral pressure variations: activity of the pelvic floor muscles and
      of the urethral sphincter muscles. For the pelvic floor, we found either slow or
      fast contractions with, respectively, slow (15-30 cm H2O for 3-10 sec) or fast
      (30-130 cm H2O for 1-3 sec) urethral pressure changes. Urethral sphincter
      contractions were always fast, resulting in fast pressure changes of 30-170 cm
      H2O for 1-3 sec. CONCLUSION: Evaluation of simultaneous perineal sonography and
      urethrocystometry shows the association of urethral pressure variations and
      muscle activity. Urethral pressure variations are caused by the activity of
      urethral sphincter or pelvic floor muscles. With ultrasound the activity of the
      urethral sphincter muscle can directly be seen whereas pelvic floor muscle
      activity is indirectly visible. Pelvic floor muscle contractions are either fast
      or slow, whereas the urethral sphincter muscle contractions are always fast
      contractions.

PMID- 9021789
TI  - Urinary bladder control by electrical stimulation: review of electrical
      stimulation techniques in spinal cord injury.
AB  - Evacuation of urine in paraplegics without the need for catheters would be
      possible when voiding could be induced by eliciting a bladder contraction. A
      challenging option to obtain detrusor contraction is electrical stimulation of
      the detrusor muscle or its motor nerves. This article reviews the 4 possible
      stimulation sites where stimulation would result in a detrusor contraction: the
      bladder wall, the pelvic nerves, the sacral roots, and the spinal cord. With
      respect to electrode application, sacral root stimulation is most attractive.
      However, in general, sacral root stimulation results in simultaneous activation
      of both the detrusor muscle and the urethral sphincter, leading to little or no
      voiding. Several methods are available to overcome the stimulation-induced
      detrusor-sphincter dyssynergia and allow urine evacuation. These methods,
      including poststimulus voiding, fatiguing of the sphincter, blocking pudendal
      nerve transmission, and selective stimulation techniques that allow selective
      detrusor activation by sacral root stimulation, are reviewed in this paper.

PMID- 9021790
TI  - Corino-Andrade disease (familial amyloidotic polineuropathy type I) in Spain:
      urological and andrological disorders.
AB  - In our hospital, we have followed a group of patients with familial amyloidotic
      polyneuropathy (FAP), type I. This disease is characterized by a progressive
      sensitive-motor and autonomic polyneuropathy. The amyloid fibrils of FAP I
      contain a mutant transthyretin (TTR) molecule. More than 90% of TTR production
      occurs in the liver. Thus, therapy with liver transplantation has proved useful.
      All our patients received this treatment. In this study we describe the
      urological and andrological disorders caused by FAP type I in 12 patients with
      low bladder pressure and bladder neck obstruction with micturition disorders. In
      some males, it was accompanied by impotence and retrograde ejaculation produced
      by autonomic neuropathy. We believe hepatic transplantation may be the best
      treatment for this disease.

PMID- 9021792
TI  - Medical therapy of BPH revisited.

PMID- 9021791
TI  - Measures of Proscar, Hytrin, and Cardura side effects.
AB  - The importance of reporting correlations among side effects is examined using
      studies of BPH drugs as examples. The special relation of placebo effects in
      studying side-effects of drugs, as opposed to their efficacies, is introduced,
      and the need for special new controls is presented.

PMID- 9021806
TI  - Colony-stimulating factors after the treatment of pediatric malignant diseases.

PMID- 9021807
TI  - St. Jude Children's Research Hospital.

PMID- 9021808
TI  - Pediatric Oncology Center of the Catholic University of Rome, Italy.

PMID- 9021809
TI  - Present status of pediatric hematology-oncology in China.

PMID- 9021810
TI  - Overview of clinical studies of childhood acute lymphoblastic leukemia for more
      than ten years by the Japanese Children's Cancer and Leukemia Study Group.
AB  - Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed
      a series of protocols for treatment of acute lymphoblastic leukemia (ALL) in
      childhood. In the first randomized controlled study of the 811 protocol (1981
      1983) a comparison of conventional daily 6-mercaptopurine and methotrexate with a
      pulsed regimen of the two drugs was performed. The superiority of the pulsed
      regimen was shown. In the next 841 protocol (1984-1987) a comparison of two drugs
      and three drugs during induction therapy was conducted. The three-drug regimen
      resulted in a significantly higher event-free survival (EFS) rate. In the 874
      protocol (1987-1990) two regimens with or without cranial irradiation were
      randomly compared, and there was no significant difference between the two
      regimens for the standard-risk group. To further improve the EFS rate a risk
      group-directed protocol 911 was conducted starting in January 1991. Life-table
      analysis of serial CCLSG protocols revealed that the outcome of overall ALL has
      gradually improved with an increase of the EFS rate; 41.4% +/- 3.6% at 14 years
      for the 811 protocol, 51.3% +/- 3.5% at 11 years for the 841 protocol, 56.7% +/-
      3.1% at 8 years for the 874 protocol, and 78.2% +/- 3.1% at 4 years for the more
      recent 911 protocol.

PMID- 9021811
TI  - Differential diagnosis based on immunological-phenotyping in suspected malignant
      bone marrow involvement in childhood.
AB  - The diagnostic value of immunophenotyping (IP) as a first-line diagnostic method
      in diseases that infiltrate the childhood bone marrow (BM) or mimic infiltrated
      BM was examined. Two hundred and fifty unselected BM samples from 250 children
      suspected to have a malignancy infiltrating their BM were evaluated by means of
      IP and conventional morophological-cytochemical (MC) studies. We applied the
      alkaline phosphatase anti-alkaline phosphatase method for IP using a panel of
      monoclonal antibodies (Mabs) against leukocyte-associated antigens,
      neuroectodermal antigens, and intermediate filament antigens. Four cases of
      neuroblastoma, two cases of Ewing sarcoma, and one case of rhabdomyosarcoma were
      diagnosed by IP but not by MC studies. In nine cases of acute leukemia bone
      marrow blasts could not be ascribed to a specific lineage on the basis of blast
      morphology or histochemistry. Eight samples without morphological evidence of
      malignant infiltration revealed an increased percentage of immature B cell
      precursors (CD10+, TdT+) suggesting acute lymphoblastic leukemia. None of these
      children has developed malignant lymphoproliferative disease. Our data suggest
      that the immunological evaluation of BM in childhood is highly capable of
      discriminating between different malignant populations but it does not recognize
      malignancy and therefore supplements but cannot replace conventional methods for
      diagnosis.

PMID- 9021812
TI  - Flow cytometric analysis of platelet surface glycoproteins in the diagnosis of
      Bernard-Soulier syndrome.
AB  - The use of flow cytometry in the diagnosis of Bernard-Soulier syndrome (BSS) in
      patients with giant platelets and thrombocytopenia was investigated as an adjunct
      to ristocetin-induced platelet aggregation (RIPA) studies because of problems
      experienced with aggregation studies, particularly at the time of presentation,
      in the pediatric age group. Eight patients suspected of having BSS were studied
      with respect to platelet expression of glycoprotein Ib alpha (CD42b) and
      glycoprotein IIIa (CD61) using an EPICS Profile II flow cytometer. Twelve
      patients with normal platelet morphology and platelet counts were used as normal
      controls. One patient with Alport's syndrome, four patients with immune
      thrombocytopenic purpura (ITP), and one patient with Glanzmann thrombasthenia
      were also studied. In all eight patients suspected of having BSS, deficiency of
      glycoprotein Ib alpha was demonstrated. Normal expression was demonstrated in 12
      control patients, in one patient with giant platelets with Alport's syndrome, and
      in four patients with ITP. Absence of glycoprotein IIIa was demonstrated in
      Glanzmann thrombasthenia. In the pediatric age group one is able to demonstrate
      abnormalities of platelet membrane glycoprotien in patients with
      thrombocytopathias using flow cytometry. This method has the advantage of being
      rapid and can be performed on small volumes of blood suitable for pediatric
      practice.

PMID- 9021813
TI  - Antipyretic effect of parenteral paracetamol (propacetamol) in pediatric
      oncologic patients: a randomized trial.
AB  - The antipyretic efficacy of propacetamol, an intravenous prodrug of paracetamol,
      was evaluated in two pediatric prospective randomized studies. In the first, we
      compared one standard intravenous dose of propacetamol (30 mg/kg) to one standard
      intravenous dose of acetylsalicylic acid (ASA, 15 mg/kg) in 10 nononcologic
      patients with bacterial illnesses. In the second study, we compared two
      intravenous doses of propacetamol (30 mg/kg versus 15 mg/kg) in 24 oncologic
      patients with fever and neutropenia. No statistically significant differences in
      antipyretic efficacy were found between standard doses of propacetamol and ASA;
      even when half-doses of propacetamol (15 mg/kg) were used, good antipyretic
      efficacy was observed, which was not statistically different from that observed
      with the full dose. The use of propacetamol seems promising for patients (such as
      oncologic patients) who cannot receive enteral paracetamol formulas.

PMID- 9021814
TI  - Beta-thalassemia alleles in Aegean region of Turkey: effect on clinical severity
      of disease.
AB  - Beta (beta) globin gene analysis was performed in 54 homozygous beta-thalassemia
      patients followed up in the Pediatric Hematology Department of Medical School of
      Ege University. The spectrum of beta-thalassemia alleles and their effect on
      clinical severity of disease were investigated. Twelve different mutations were
      determined in our patients. The six most frequent alleles, IVSI-110 (G-A), IVSI-6
      (T-C), IVSI-I (G-A), IVSII-745 (C-G), Cd39 (C-T), and FSC8, account for 80.6% of
      all the disease genes. Eleven percent of the chromosomes could not be identified
      with the probes used in this study. In 38 patients both of whose beta-thalassemia
      alleles were identified, the beta-thalassemia alleles were found to be the major
      determinant of the clinical severity of disease. The clinical progress of disease
      was also closely related to the degree of iron overload.

PMID- 9021815
TI  - Bone marrow transplantation in patients with Fanconi anemia: experience with
      cyclophosphamide and total body irradiation conditioning regimen.
AB  - Eleven patients with Fanconi anemia (FA) underwent bone marrow transplantation
      (BMT) between March 1985 and May 1990 in a single institution. Ten patients
      received bone marrow from healthy full human leukocyte antigen (HLA) matched
      siblings and one patient from her father (one antigen mismatch). Ten patients
      were conditioned with cyclophosphamide (Cy) at a dose of 5 mg/kg per day for 4
      days followed by total body irradiation (TBI) for a total of 600 cGy over 3 days.
      Six of the 11 patients are alive and have normal reconstitution of their bone
      marrow. Median follow-up was 72 months (range 42-84). Three of the 10 patients
      who received Cy and TBI (two HLA compatible, one antigen mismatch) had graft
      failure. Five patients developed at least grade III acute graft-versus-host
      disease (GVHD). The rates of graft failure and GVHD are, however, still
      significantly high. Modification of the conditioning regimen and GVHD prophylaxis
      is needed to improve the outcome.

PMID- 9021816
TI  - Engraftment failure following bone marrow transplantation in children with
      thalassemia major using busulfan and cyclophosphamide conditioning.
AB  - Thirteen children older than 3 years of age with beta-thalassemia major underwent
      allogeneic bone marrow transplantation (BMT) from a full human leukocyte antigen
      (HLA) matched sibling donor in a single institution. These patients received
      busulfan (Bu). 16 mg/kg followed by cyclophosphamide (Cy) 200 mg/kg for
      conditioning. Eight of the 13 patients (Group 1) engrafted and have a median age
      of 13 years (range 5-15 years). The five patients (Group 2) who failed to engraft
      have a median age of 6 years (range 3-8 years). The association with the
      following factors was found to be statistically significant: age (older in Group
      1), duration of nadir of white blood count (WBC) of < or = .1 x 10(9)/L (longer
      in Group 1), and the dose of Bu administered to each patient calculated on the
      basis of body surface area (higher dose in Group 1). The high rate of engraftment
      failure (5 out of 13) may be related to the suboptimal systemic exposure of Bu in
      younger children leading to inadequate bone marrow ablation when the standard
      dose of 16 mg/kg is used.

PMID- 9021817
TI  - Spindle cell carcinoma of the tongue in a long-term survivor of childhood acute
      lymphoblastic leukemia.
AB  - A 25-year-old male previously treated (age 9 years) for acute lymphoblastic
      leukemia developed a spindle cell carcinoma of the tongue. Possible causes for
      the development of his second malignancy are discussed. A combination of scatter
      from cranial irradiation, poor oral hygiene, alcohol consumption, and cigarette
      smoking is likely to be contributory. Genetic predisposition can never be fully
      excluded.

PMID- 9021818
TI  - Epstein-Barr virus-associated malignant lymphoma with macroamylasemia and
      monoclonal gammopathy in a patient with Wiskott-Aldrich syndrome.
AB  - A 1-year-old boy with Wiskott-Aldrich Syndrome (WAS) who developed malignant
      lymphoma is described. He showed various complications such as atypical
      lymphocytosis, disseminated intravascular coagulation (DIC), intracranial
      hemorrhage, macroamylasemia, and monoclonal gammopathy (immunoglobulin A kappa
      chain). Epstein-Barr virus (EBV) DNA was detected in the tumor tissue, and the
      monoclonality of B cells from the tumor tissue was established. EBV-associated
      lymphoma is frequently observed in immunocompromised patients including those
      with WAS. The development of macroamylasemia, which is rare in childhood, is
      discussed in relation to lymphoma and monoclonal gammopathy. This case is unique
      in that the EBV-associated malignant lymphoma developed at an early age and was
      accompanied by macroamylasemia.

PMID- 9021819
TI  - Treatment of acute immune thrombocytopenia (ITP) in childhood with a single dose
      of intravenous immunoglobulin.

PMID- 9021820
TI  - Safety of dexrazoxane in children with all undergoing anthracycline therapy:
      preliminary results of a prospective pilot study.

PMID- 9021821
TI  - Prenatal sexing of human fetuses and selective abortion.

PMID- 9021822
TI  - Single umbilical artery--right or left? does it matter?
AB  - Ultrasonographic prenatal diagnosis of single umbilical artery (UA) is well
      documented, but the exact siding of the single UA and its correlation with the
      occurrence of other congenital malformations and the outcome of the baby remain
      unclear. We report our experience with 46 cases of prenatally diagnosed single
      UA. This is the first prospective study of a large number of consecutive
      pregnancies in which the side of the existing artery was identified in fetuses
      with a single UA. Most of the cases were identified by transvaginal sonography at
      14-16 weeks' gestation. A right artery was detected in 25 fetuses (54.3 per
      cent), and a left artery in 21 cases (45.7 per cent). Six fetuses (13 per cent)
      had associated anomalies, five of them in the urinary system. No correlation was
      found between the type or severity of the malformations and the side of the
      missing (or existing) UA. In our experience, the exact location of the single UA
      can be reliably determined by ultrasonography from the beginning of the second
      trimester of pregnancy. The selection process of the missing (or existing) vessel
      is likely to be random, even though a right single artery was seen slightly more
      often.

PMID- 9021823
TI  - Assay of gamma-glutamyl transpeptidase activity in amniotic fluid offers a
      possible prenatal diagnosis of biliary atresia in the rat model.
AB  - Muller et al. analysed gamma-glutamyl transpeptidase (GGTP) activity in the
      amniotic fluid of more than 2000 pregnant women for a prenatal diagnosis. They
      reported that at 18-19 weeks' gestation, two fetuses associated with lower
      amniotic fluid GGTP levels were diagnosed after birth as having biliary atresia
      (BA). If low GGTP values correlate closely with BA, chemical assay of amniotic
      fluid GGTP could possibly be used in the prenatal diagnosis of BA. A fetal model
      of cholestasis in the rat was created by the administration of the toxic
      cytopharmacological agent phalloidin on day 15 of gestation, after which amniotic
      fluid was aspirated and analysed for GGTP. Fetal liver specimens were examined
      histopathologically. In the normal rats, amniotic fluid GGTP values rose rapidly
      after 18 days 8 h, reaching a maximum value at 19 days of gestation.
      Significantly lower GGTP values were observed in the cholestasis models between
      18 days 16 h and 19 days 16 h of gestation (P < 0.05). Our data corroborate
      Muller et al.'s suggestion that fetuses with cholestasis might demonstrate lower
      GGTP values in their amniotic fluid at a given stage of gestation. Prenatal
      diagnosis of BA using the amniotic fluid GGTP assay therefore has considerable
      potential.

PMID- 9021824
TI  - Prenatal diagnosis, pathology, and genetic study of fetus in fetu.
AB  - We report the prenatal diagnosis, pathology, cytogenetics, and molecular studies
      of a retroperitoneal fetus in fetu. Prenatal ultrasonography of the host fetus in
      the third trimester showed an anencephalic, acardiac mass with identifiable
      extremities and spine within an intra-abdominal cystic mass. Pathological
      examination revealed a fetiform mass weighing 20 g with four extremities, digits,
      vertebral bodies, an oral cavity with developing teeth, primitive male external
      genitalia, a urinary bladder, a cloaca with an external opening, large
      intestines, a membranous capsule, and an umbilical cord with one artery, one
      vein, and Wharton's jelly. Histological examination demonstrated nerve bundles in
      the fibrocollagenous tissue below the cuboidal surface epithelium of the
      membranous capsule, and absence of lamina elastica interna and vasa vasorum in
      the single artery of the umbilical cord. Both the host infant and the fetus in
      fetu had a normal 46,XY karyotype. Molecular analysis using informative genetic
      markers showed no genetic difference between the host infant and the fetiform
      mass. We report this case as an unusual example of fetus in fetu in co-existence
      with an amnion-like membrane containing nerve bundles and with a well-formed
      umbilical cord. We demonstrate that fetus in fetu can be diagnosed prenatally if
      the fetiform mass has well-developed limbs and spine. We emphasize the necessity
      for suspicion of fetus in fetu when a well-defined encapsulated cystic mass with
      calcified solid components is detected prenatally in a fetus by ultrasonography.

PMID- 9021825
TI  - Criteria for fetal nuchal thickness cut-off: a re-evaluation.
AB  - An attempt has been made to establish a more effective cut-off criterion for
      nuchal thickness (NT) and to assess the optimal gestational period for the
      prediction of trisomies 21 and 18. Reference intervals were established for NT
      from the tenth to the 18th week, using either gestation-specific centiles or the
      parametric method. The measurements in 47 consecutive trisomy 21 and 18 trisomy
      18 cases were plotted against these intervals. Assaying different cut-off
      criteria for both the centile and the parametric methods, sensitivities and false
      positive rates for each gestational week were calculated and then compared with
      the commonly applied 'two-stepped' cut-off method (3 mm early, 6 mm later). The
      parametric method, based on a progressive rise, with +2.5 SD for the
      corresponding gestational week as a cut-off value, showed the best performance
      (likelihood ratio 38) in the prediction for trisomy 21. The optimal gestational
      age was the 12-18 week period, with an overall sensitivity of 62 per cent (23/37)
      for an average false-positive rate of 0.7 per cent. For trisomy 18, the most
      effective cut-off was also +2.5 SD, and 10-13 gestational weeks as the optimal
      period, achieving 86 per cent (6/7) sensitivity for a 1.9 per cent false-positive
      rate.

PMID- 9021826
TI  - Biochemical markers of trisomy 21 in amniotic fluid.
AB  - In a study of amniotic fluid from 91 Down's syndrome cases and 240 controls, we
      have shown that the median values of four biochemical markers (AFP, total hCG,
      free beta hCG, and unconjugated oestriol) in the amniotic fluid of pregnancies
      affected by Down's syndrome on the whole reflect those observed in the maternal
      serum of affected cases. The median MOM for AFP was lower than average (0.56), as
      was that for unconjugated oestriol (0.55), whilst those for total hCG (1.82) and
      free beta hCG (2.10) were increased on average. The width of the distribution of
      marker levels in amniotic fluid is similar to that in serum for free beta hCG and
      total hCG but between 1.5 and 2 times wider for unconjugated oestriol and AFP.
      Analysis of data by fetal sex showed a significantly higher median MOM in female
      control cases compared with male controls for the analytes free beta hCG, total
      hCG, and unconjugated oestriol, but not for AFP. Amongst the Down's syndrome
      cases, this trend was not statistically significant and we cannot confirm a
      previous study which reported that elevated levels of amniotic fluid total and
      free beta hCG were associated only with female fetuses.

PMID- 9021827
TI  - Between-pregnancy biological variability of maternal serum alpha-fetoprotein and
      free beta hCG: implications for Down syndrome screening in subsequent
      pregnancies.
AB  - In women who have an increased Down syndrome risk in a first pregnancy there is a
      five-fold greater chance of also having an increased Down syndrome risk in a
      second subsequent pregnancy. Similarly, in women who have a high alpha
      fetoprotein (AFP) level in the first pregnancy, suggesting an increased risk of a
      neural tube defect (NTD), there is also a five-fold greater chance of them also
      having a high result in a second subsequent pregnancy. Such a biological
      association of serum marker levels between pregnancies suggests that there are
      additional maternal or genetic factors influencing the levels of these serum
      markers, other than the physiological factors which in themselves are poorly
      understood. In theory, it is possible to correct for high/low marker results in a
      previous pregnancy and to do so, I estimate, would reduce the overall Down
      syndrome screening false-positive rate by about 0.2 per cent. There are
      insufficient data to make any prediction regarding the impact on detection rates.
      The small reduction in false-positive rate is unlikely to be a feature worth
      implementing in Down syndrome screening programmes.

PMID- 9021829
TI  - Prenatal diagnosis of facial malformations.
AB  - In a prospective study, 5407 pregnant women were screened by ultrasound to detect
      malformations of the fetal face. Of a total of 11 facial anomalies, eight were
      detected by prenatal ultrasound (72 per cent). Three pregnancies were terminated
      because of associated developmental abnormalities or aneuploidy. In all of them,
      the facial malformations were correctly diagnosed. When associated with other
      developmental abnormalities, facial malformations were picked up at a rate of 100
      per cent. Isolated facial malformations, by contrast, were detected in no more
      than 50 per cent of cases. Eight cases with suspected facial dysmorphism ended
      with the delivery of normal babies (specificity 99.8 per cent). None of them
      prompted karyotyping or any other invasive testing. Only two correctly detected
      facial malformations (bilateral cleft lips/palate) had a minor influence on
      obstetrical management. There would not have been disadvantages for the newborns
      in any of the cases if the malformations had been missed.

PMID- 9021828
TI  - Maternal serum alpha-fetoprotein and epithelial tumour marker concentrations are
      not increased by fetal sacrococcygeal teratoma.
AB  - Maternal serum alpha-fetoprotein (AFP) and total beta-human chorionic
      gonadotrophin (hCG) concentrations were measured at the 15th gestational week in
      ten pregnancies complicated by fetal sacrococcygeal teratoma. The findings
      corresponded to those in normal pregnancies. Similarly, third-trimester
      concentrations of cancer antigen 12-5, tumour-associated trypsin inhibitor, and
      the amino-terminal propeptide of type III procollagen in the maternal serum were
      not significantly elevated. Histologically mature and immature/malignant cases
      did not differ from each other as regards the above-mentioned parameters. This
      abnormality cannot be detected by maternal serum trisomy screening in the second
      trimester.

PMID- 9021830
TI  - Maternoembryonic transfusion and congenital malformations.
AB  - There is an increasing number of reports relating chorionic villus sampling (CVS)
      to transverse limb reduction defects or the oromandibular limb hypogenesis
      complex. In addition, a correlation has been established between the severity of
      the defect and the gestational age when CVS is performed. Several hypotheses have
      been proposed for the increased incidence of congenital malformations after CVS
      including vascular disruption. Recently, it has been suggested that
      maternoembryonic transfusion can occur after CVS and that this can lead to a
      local antibody-mediated reaction, followed by local pathogenetic cell
      degeneration, i.e., apoptotic cell death, due to vascular disruption. This
      increased apoptotic cell death will ultimately result in congenital
      malformations. This paper describes an experimental model that can explain the
      pathogenesis of congenital malformations after CVS. The model designed uses a
      whole rat embryo culture technique and intracardiac injection of antisera,
      mimicking transplacental transfusion after CVS. Injection of antibodies directed
      against blood group antigens is capable of inducing increased apoptotic cell
      death. Immunological staining gives evidence of involvement of antibody-mediated
      reactions in the occurrence of apoptotic cell death. The dorsal aortae in 10-day
      old rat embryos of 10-somite stages of development consist of a continuous
      endothelial cell layer. The effect of intracardiac injection of antisera on the
      dorsal aortae is only transient. Smaller vessels such as the pharyngeal arch
      arteries or arteries of the limbs still have fenestrated endothelium and are
      therefore more vulnerable to the pathogenetic effect of the reaction after
      transplacental transfusion causing vascular disruption. Development of the
      vascular pattern and differentiation of the vascular wall reduce the risk of
      severe malformations later on in pregnancy, although the risk of malformations
      remains throughout pregnancy. Thus, intracardiac injection of antisera simulating
      maternoembryonic transfusion such as after CVS can lead to an antibody-mediated
      reaction with vascular disruption early in pregnancy inducing apoptotic cell
      death. Increased cell death may ultimately result in congenital malformations,
      such as transverse limb defects or the oromandibular limb hypogenesis complex.

PMID- 9021831
TI  - Chorionic villus sampling and end-artery disruption of the fetus.
AB  - A fetus with transverse limb reduction defects and jejunal atresia after exposure
      to chorionic villus sampling (CVS) at 9 weeks of amenorrhoea is described. A
      theory involving disruption of end-arteries due to the CVS procedure is
      suggested.

PMID- 9021832
TI  - Severe limb reduction defects after uterine lavage at 7-8 weeks' gestation.
AB  - A 35-year-old multiparous Chinese woman underwent a uterine lavage procedure for
      prenatal sex determination at 7-8 weeks' gestation. The baby was delivered by
      elective Caesarean section because of breech presentation at 38 weeks' gestation.
      The child weighed 2425 g and had severe reduction defects of all four limbs. This
      case warrants advising prospective patients of a possible association and
      encouraging practitioners to mount a careful prenatal ultrasonography and
      postnatal follow-up of all pregnancies investigated by prenatal diagnostic
      uterine lavage.

PMID- 9021834
TI  - Syndromic forms of hydrometrocolpos.

PMID- 9021833
TI  - Maternal uniparental disomy for chromosome 22 in a child with generalized
      mosaicism for trisomy 22.
AB  - We report on a case of generalized mosaicism for trisomy 22. At chorionic villus
      sampling (CVS) in the 37th week of pregnancy, a 47,XX,+22 karyotype was detected
      in all cells. The indication for CVS was severe unexplained symmetrical
      intrauterine growth retardation (IUGR) and a ventricular septal defect (VSD) was
      noted. In cultured cells from amniotic fluid taken simultaneously, only two out
      of ten clones were trisomic. At term, a growth-retarded girl with mild dysmorphic
      features was born. Lymphocytes showed a normal 46,XX[50] karyotype; both
      chromosomes 22 were maternal in origin (maternal uniparental disomy).
      Investigation of the placenta post-delivery using fluorescence in situ
      hybridization showed a low presence of trisomy 22 cells in only one out of 14
      biopsies. In cultured fibroblasts of skin tissue, a mosaic 47,XX,+22[7]/46,XX[25]
      was observed. Clinical follow-up is given up to 19 months.

PMID- 9021835
TI  - A false-positive diagnosis of Turner syndrome by amniocentesis.

PMID- 9021837
TI  - Current awareness in prenatal diagnosis.

PMID- 9021836
TI  - An additional report of prenatal detection of mosaic isochromosome 20q at
      amniocentesis.

PMID- 9021838
TI  - Assessment of service needs of adult psychiatric inpatients: a systematic
      approach.
AB  - In this study, a systematic needs-assessment approach to evaluating the
      institutional and community service requirements of adult psychiatric inpatients
      is reported. The Community Placement Questionnaire (CPQ) was completed by
      professional staff on all patients between the ages of 18-65 residing in a
      publicly-funded psychiatric hospital. Of the 105 patients surveyed, 65.7% were
      considered potentially hard to place in the community (6.7% were nominated for
      permanent placement in the institution), and 34.3% were considered easy to place.
      The findings indicate that successful planning for community-based mental health
      services requires the four essential elements of the protected hospital
      environment, treatment, augmentation in psychosocial rehabilitation programming
      and availability of supports and services in the community. Specific strategies
      for transition from institutional-based care to community care are discussed.

PMID- 9021839
TI  - Clinical and human resource planning for the downsizing of psychiatric hospitals:
      the British Columbia experience.
AB  - Riverview Hospital, B.C.'s only and Canada's largest remaining provincial
      psychiatric hospital began a formal planned "downsizing" process in 1992. This
      initiative was an important element in the Province's strategic plan to shift to
      a more community-focused mental health system and to bring tertiary psychiatric
      services "closer to home" by redeveloping Riverview Hospital on three sites. The
      paper summarizes the literature pertaining to the "downsizing" of psychiatric
      hospital services in relation both to clinical and human resource planning. It
      describes the mental health system in B.C. and the service system context in
      which this exercise is occurring. It is based on the first three years of
      experience in identifying the major challenges and the strategies developed to
      meet these challenges. It draws some conclusions about the effectiveness of these
      strategies and it speculates about the likely future challenges as the
      "downsizing" process continues.

PMID- 9021840
TI  - Leadership crisis in psychiatric services: a change theory perspective.
AB  - In 1990, after twenty years of service, the psychiatrist who had been Director of
      Psychiatric Services at Alpha Hospital decided to take an early retirement. What
      followed was a dramatic leadership struggle, which peaked with the resignation
      (in the summer of 1992) of most of the hospital's psychiatrists. In the years
      since, there has been a great deal of healing. The psychiatrists are all back at
      work. Joint leadership of the services is established under the direction of a
      (psychiatrist) Clinical Director and a (non-psychiatrist) Administrative
      Director. Management of the programs and services has been reorganized to a much
      more efficient and effective system. And feelings among the key players are more
      trusting and collaborative. This paper will explore how this crisis may be
      understood in terms of change theory. It will also outline the process utilized
      to resolve the crisis, and will draw implications for other mental health
      administrators who, in these times of rapid and dramatic change, will undoubtedly
      confront similar challenges.

PMID- 9021841
TI  - Hospital downsizing and patients' assaults on staff.
AB  - Although the downsizing and closing of state mental hospitals is occurring with
      increasing frequency nationwide, there appears to be only one case study of the
      clinical impacts of downsizing state hospitals. In this study, Snyder reported a
      four-fold increase in frequency of assaults on staff as the hospital census
      decreased. The present paper is a second case study of state hospital downsizing
      and closing in which the frequency of assaults on staff decreased by 63%.
      Possible explanations for the two differing outcomes are considered, and some
      general guidelines for the downsizing and closing of state hospitals are
      proposed.

PMID- 9021842
TI  - Community Treatment Teams: an alternative to state hospital.
AB  - This article describes the implementation of Community Treatment Teams as a
      strategy to provide services to patients discharged from a state psychiatric
      hospital. The closing of Philadelphia State Hospital was the impetus for the
      development of an alternative long term care treatment system for the seriously
      mentally ill which was based on a variation of the community treatment team
      model. This article provides a description of the teams, their functioning,
      structure, and the impact they have had on the service system.

PMID- 9021843
TI  - Psychiatric survivors and nonsurvivors.

PMID- 9021845
TI  - Treatment of VA inpatients with diagnoses of substance abuse.

PMID- 9021844
TI  - Mental health parity: clarifying our objectives.

PMID- 9021846
TI  - High utilization of inpatient psychiatric services by older adults.

PMID- 9021847
TI  - Psychosocial predictors of HIV risk among adolescent offenders who abuse drugs.

PMID- 9021848
TI  - Integrating mental health into the Oregon Health Plan.

PMID- 9021849
TI  - Lack of insight among outpatients with schizophrenia.
AB  - OBJECTIVE: This study investigated the prevalence of lack of insight among
      outpatients with schizophrenia and the relationship between lack of insight and
      other variables, including whether patients received professional residential
      supervision. METHODS: A total of 87 stable outpatients with schizophrenia were
      drawn from community programs in a public-private mental health system. Subjects'
      clinical symptoms and insight about their illness were assessed using the
      Positive and Negative Syndrome Scale, a battery of neuropsychological tests, and
      the Social Functioning Scale. RESULTS: The illness insight of 43 subjects, or
      49.5 percent, was at least moderately impaired. Twenty-one subjects, or 25
      percent, had severe insight deficits. In a multiple regression analysis, 40
      percent of the variance in lack of insight was predicted by ratings of the
      severity of delusions, difficulty with abstract thinking, lack of social
      activities, and absence of anxiety. Patients who received professional
      residential supervision had more impaired insight than those living independently
      or with family. CONCLUSIONS: Insight deficits are common among stable outpatients
      engaged in community-based care. These deficits have implications for patients'
      use of limited services such as residential supervision.

PMID- 9021850
TI  - Outcomes of patients in a VA ambulatory detoxification program.
AB  - OBJECTIVE: The study examined outcomes of patients enrolled in a Veterans Affairs
      ambulatory detoxification program. METHODS: Descriptive statistical data were
      collected by routine clerical processes at a VA medical center. Patients'
      outcomes were operationally defined to include completion of the detoxification
      program, dropout or discharge, or re-enrollment in the program; admission to
      inpatient detoxification; and referral to, entry into, and completion of
      substance abuse rehabilitation after detoxification. Outcomes were determined for
      517 of the 577 patients consecutively referred to the program during nine months
      in 1995. Patients met established criteria for mild to moderate alcohol
      withdrawal syndrome. RESULTS: Of the 517 patients, 453 successfully completed
      outpatient detoxification. Twenty patients dropped out, 19 were discharged, 37 re
      enrolled, and 25 were admitted for inpatient detoxification. Of the 453 patients
      who completed outpatient detoxification, 434 were referred for further treatment;
      415 entered and 322 completed the next treatment phase. CONCLUSIONS: The
      completion rate for patients in the outpatient detoxification program and rates
      for continuing and completing further treatment were higher than in previous
      studies. Measures of poor short-term outcome (dropout, re-enrollment, and
      admission to inpatient detoxification) also compared favorably with previous
      studies. Unique factors contributing to outcomes included systematic screening,
      medical protocols for detoxification, psychosocial therapies, program-supported
      housing, and attention to patient satisfaction.

PMID- 9021851
TI  - The impact of hospitalization on clinical assessments of suicide risk.
AB  - OBJECTIVE: Clinicians' assessments of patients' suicide risk at admission to and
      discharge from a psychiatric hospital were examined to learn how clinical
      estimates of risk changed over the course of hospitalization and to identify
      which demographic and clinical characteristics were associated with higher
      estimates of risk at admission and discharge. METHODS: Seventy-one treating
      physicians evaluated risk of self-harm of 241 patients at admission to and
      discharge from a short-term inpatient unit. Risk within the next week (short-term
      risk) and within the next year (long-term risk) was estimated. At discharge and
      admission, the physicians also rated patients' symptoms using the Brief
      Psychiatric Rating Scale. Nurses rated self-directed aggression during
      hospitalization with the Overt Aggression Scale. RESULTS: Ratings of short-term
      risk were lower at discharge than at admission, whereas ratings of long-term risk
      showed relatively little change. At both discharge and admission, the estimated
      risk of self-harm was associated with a history of suicidal behavior and with
      acute symptoms, such as depression, anxiety, and emotional withdrawal. At
      discharge, the estimated risk was also associated with substance abuse, severity
      of psychosocial stressors, and living alone. CONCLUSIONS: Clinicians appeared to
      view their hospital-based interventions as influencing variables relevant to
      short-term risk of suicide but as having little impact on long-term risk.
      Implications are discussed for management of suicide risk and for medicolegal
      assertions regarding prevailing community practices that are made in litigation
      alleging negligent release of patients from hospitals.

PMID- 9021852
TI  - Clinical implications of respect for autonomy in the psychiatric treatment of
      pregnant patients with depression.
AB  - Major depression, as well as depressive symptoms that do not meet the full
      diagnostic criteria for a diagnosis of depression, can chronically and variably
      affect a woman patient's decisions about the management of pregnancy, including
      the decision about whether to continue a pregnancy. Depression also has potential
      adverse consequences for the pregnant woman and her pregnancy. However, little
      attention has been given to the ethical challenges posed by the psychiatric
      management of depression during pregnancy. The psychiatrist should balance
      respect for the autonomy of the depressed woman with beneficence-based
      obligations to the pregnant woman, and also to the fetus, when the fetus is
      viable. The authors recommend strategies for assessing the decision-making
      abilities of pregnant patients with depression and for enhancing their autonomy.
      They suggest that nondirective counseling should generally be used with pregnant
      patients with depression when the fetus is previable and that directive
      counseling is ethically justifiable when the fetus is viable.

PMID- 9021853
TI  - Utilization of neuroleptic drugs in Italian mental health services: a survey in
      Piedmont.
AB  - OBJECTIVE: This survey describes neuroleptic prescribing practices in Italian
      mental health services 15 years after implementation of a mental health reform
      law that shifted the focus of care from mental hospitals to community services.
      METHODS: The authors conducted a cross-sectional survey of neuroleptic
      prescribing practices in several psychiatric services throughout the Piedmont
      region in northern Italy. The relationship between dosing patterns and patients'
      characteristics was assessed using multiple regression analysis. RESULTS: Sixty
      six community mental health services and 14 psychiatric wards in general
      hospitals participated in the survey in 1991. Among the 3,823 psychiatric
      patients seen in these settings for whom survey data were available, 67 percent
      of outpatients and 84 percent of inpatients were prescribed neuroleptic drugs.
      Twenty-eight percent of outpatients and 45 percent of inpatients received more
      than one neuroleptic. The average daily dose of neuroleptics was low to moderate;
      89 percent of outpatients and 67 percent of inpatients received 500 mg of
      chlorpromazine equivalents or less. The neuroleptic dose was significantly
      associated with patients' age, education, diagnosis, length of treatment, and
      receipt of polypharmacy. CONCLUSIONS: This survey confirms the low to moderate
      neuroleptic dosing in Italian mental health services, both in outpatient and
      inpatient settings. However, it also documents the widespread use of
      polypharmacy, a pattern that has remained largely unchanged over the past 15
      years.

PMID- 9021854
TI  - The pattern-of-care model: a tool for planning community mental health services.
AB  - In periods of change, psychiatric services must project outcomes of decisions
      about service innovations and reductions, including budgetary implications. To
      support such decision making, a public-sector psychiatric service in Melbourne,
      Victoria, Australia, developed a modeling tool that combines data from its
      service activity database and budgetary information with modeling techniques
      based on use of a spreadsheet. The model is based on clients' use of three major
      service components: the inpatient unit, continuing clinical care and consultancy
      services, and crisis assessment and treatment services. It classifies clients
      according to patterns of care-that is, whether they used one, two, or three of
      the components, in various combinations. The authors report service use and
      financial data derived from the model for the financial year 1992-1993. They
      describe two scenarios for using the model to project changes in patterns of care
      and costs when new services are implemented. Such a model can clarify costs,
      including opportunity costs, of management decisions and facilitate participation
      of senior clinicians in active service planning within the realities of budgetary
      constraints.

PMID- 9021855
TI  - Assessment of the quality of life of patients with major depression.
AB  - OBJECTIVE: This study examined the relationship between a measure of quality of
      life and measures of depressive symptoms among patients with major depression.
      METHODS: One hundred patients with primary major depression and 61 control
      subjects from the San Diego Veterans Affairs Medical Center and surrounding area
      were compared using a variety of measures, including the Quality of Well-Being
      (QWB) scale, the Hamilton Rating Scale for Depression, and the Beck Depression
      Inventory. RESULTS: After analyses controlled for age, gender, family history of
      mental illness, and comorbid axis III diagnosis, subjects' scores on the QWB were
      significantly correlated with their scores on the Hamilton scale and Beck
      inventory. The severity of depressive symptoms was inversely related to quality
      of life as measured by the QWB, independent of the variables that were controlled
      for. CONCLUSIONS: The QWB is sensitive to symptoms of depression among patients
      diagnosed with major depression. The reduction in quality of life associated with
      psychiatric symptoms of depression is comparable to that observed among
      physically ill patients.

PMID- 9021856
TI  - Implementation of total quality management after reconfiguration of services on a
      general hospital unit.
AB  - In 1992 the New York State Office of Mental Health issued a statewide plan for
      mental health services to reduce the number of inpatient beds in state-run
      facilities from approximately 11,000 to between 6,000 and 8,000 by the year 2000.
      This reduction resulted in at least a 25 percent increase in psychiatric beds at
      local general hospitals. In 1992 Albany Medical Center Hospital's department of
      inpatient psychiatry established an interdisciplinary committee to address
      changes resulting from the reconfiguration of services to chronic mentally ill
      persons. The committee established procedures to use the principles of total
      quality management to respond to problems and to continuously improve the
      therapeutic milieu. The authors describe how these principles were used to create
      a patient satisfaction survey, to examine and improve part of the hospital
      admissions procedure, and to review and revise treatment planning documentation.
      A concurrent review committee reviews patients' records to ensure accuracy of
      documentation and quality of care.

PMID- 9021857
TI  - Incidence of HIV infection among patients with new-onset psychosis.
AB  - To assess the frequency of HIV testing and the incidence of HIV infection among
      patients with new-onset psychosis, the records of 811 patients referred to a
      military hospital for acute psychosis during a two-year period were reviewed.
      Records of 518 patients were excluded because they had known chronic psychotic
      illnesses, repeat admissions for recurrent affective disorders with psychotic
      features, delirium, dementia, or pre-existing HIV infection. Of the 293 patients
      with new-onset psychotic illness, 84 percent (N = 246) were tested for HIV
      antibodies. None were seropositive for HIV. Although patients with new-onset
      psychosis were commonly assessed for HIV infection to clarify their diagnosis,
      HIV infection was not associated with new-onset psychosis.

PMID- 9021858
TI  - Housing outcomes for homeless adults with mental illness: results from the second
      round McKinney program.
AB  - In the early 1990s the National Institute of Mental Health sponsored projects in
      four cities that served a total of 896 homeless mentally ill adults. Each project
      tested the effectiveness of different housing, support, and rehabilitative
      services in reducing homelessness. Most homeless individuals resided in community
      housing after the intervention. The proportion in community housing varied
      between sites. A 47.5 percent increase in community housing was found for those
      in active treatment conditions. At final follow-up, 78 percent of participants in
      community housing were stably housed. The findings indicate that effective
      strategies are available for serving homeless individuals with severe mental
      illness.

PMID- 9021859
TI  - A combined inpatient and partial hospital program.
AB  - This paper describes a combined inpatient and partial hospital program, with a
      ten-bed short-term inpatient unit and a partial hospital program that can
      accommodate 24 patients. Inpatients and partial hospital patients are treated
      together by the same staff in a program located in the partial hospital. The
      authors highlight features of the program that address the five elements of
      continuity: place, personnel, program, patient-peers, and plan for treatment. The
      discussion focuses on the importance of continuity in sustaining a combined unit;
      potential benefits for patients, families, staff, and trainees; attractiveness to
      third-party payers; and impediments to fully realizing the potential of the unit.

PMID- 9021860
TI  - Prevalence of dissociative disorders in an acute care day hospital population.
AB  - To estimate the prevalence of dissociative disorders in a day hospital and
      examine their relation to traumatic experiences, trained clinicians evaluated 70
      of 229 patients consecutively admitted to an acute care day hospital. They used
      the Mini-Structured Clinical Interview for DSM-III-R Dissociative Disorders and
      the Traumatic Experience Questionnaire. Six of the 70 patients (9 percent)
      received a definite diagnosis of a dissociative disorder. Five of the six
      patients reported a childhood history of sexual or physical abuse. The results
      show that dissociative disorders are not rare among general psychiatric patients
      in a day hospital setting and are associated with histories of childhood trauma.

PMID- 9021861
TI  - Social dominance and 22-year all-cause mortality in men.
AB  - OBJECTIVE: Research findings suggest that, in addition to hostility, social
      dominance-related variables may be related to morbidity and mortality. The
      purposes of the present study were to evaluate a) whether pressured social
      dominance (defined as a pattern of structured-interview-defined characteristics
      of verbal competition, immediateness of response, and fast speaking rate) was
      related to long-term health outcomes, namely, all-cause mortality, and b) whether
      individuals characterized by other patterns of structured-interview-derived
      characteristics also varied in terms of mortality. METHOD: The present study
      represents an analysis of the data from the 22-year mortality follow-up of 750
      men from the Western Collaborative Group Study. Cluster analytic techniques were
      used to classify individuals according to their speech and behavioral
      characteristics during a structured interview. Cox proportional hazards models
      were used to test the association between the behavioral characteristics and the
      risk of all-cause mortality. RESULTS: The pattern of characteristics reflecting
      pressured social dominance was found to be positively related to mortality (RR =
      1.6, 95% CI = 1.1-2.4, p < .02); this relation held after controlling for
      diastolic blood pressure, total cholesterol, and smoking status at study entry,
      and also after controlling for hostility. In addition, the pattern of
      characteristics in which hostility was salient was found to be positively related
      to mortality (RR = 1.5, 95% CI = 1.1-2.2, p < .02). Finally, a pattern of
      characteristics that suggests placid individuals who are neither hostile nor
      socially dominant was found to be significantly negatively related to mortality
      (RR = .638, 95% CI = .419-.974, p < .04). CONCLUSIONS: These results suggest
      that, in future research concerning psychosocial factors and long-term survival,
      attention should be given to social dominance as well as to hostility.

PMID- 9021862
TI  - Learning to have psychosomatic complaints: conditioning of respiratory behavior
      and somatic complaints in psychosomatic patients.
AB  - OBJECTIVE: Assuming a subjective similarity between the experience of a
      hyperventilation episode and inhaling CO2-enriched air, we tested whether a
      respiratory challenge in association with a particular stimulus could result in
      altered respiratory behavior and associated somatic complaints upon presenting
      the stimulus only. METHOD: Psychosomatic patients (N = 28) reporting
      hyperventilation complaints participated in a differential conditioning paradigm
      using odors with a positive or negative valence as conditioned stimuli (CS+ or CS
      ) and 7.4% CO2-enriched air as the unconditioned stimulus (US). Three CS+ and
      three CS-acquisition trials were run. During the test phase, two CS(+)- and two
      CS(-)-only trials were run, followed by two new test odors (with a positive or
      negative valence). Respiratory frequency, tidal volume, end-tidal fractional
      concentration of CO2, and heart rate were measured throughout the experiment.
      Somatic complaints were registered after each trial. RESULTS: We observed a)
      increased respiratory frequency and an elevated level of somatic complaints upon
      presenting the CS+ only; b) a selective association effect: conditioning was only
      apparent with the negatively valenced CS+ odor; (c) no generalization of
      respiratory responses and complaints to the new odors; (d) no conditioning effect
      on dummy complaints that are usually not reported when inhaling CO2; (e) in
      exploratory comparisons with normal subjects, stronger conditioning effects on
      typical hyperventilation complaints in patients, and, in female subjects, on
      respiratory frequency. CONCLUSION: Respiratory responses and psychosomatic
      complaints can be elicited by conditioned stimuli in a highly specific way. The
      findings are relevant for disorders in which respiratory abnormalities and/or
      psychosomatic complaints may play a role and for multiple chemical sensitivity.

PMID- 9021863
TI  - Screening for depression in diabetes using the Beck Depression Inventory.
AB  - OBJECTIVE: The purpose of this study was to determine the utility of the Beck
      Depression Inventory (BDI) as a screening tool for major depression in diabetes.
      METHOD: One hundred seventy-two diabetic outpatients (insulin-dependent diabetes
      mellitus [IDDM] = 59, or non-insulin-dependent diabetes mellitus [NIDDM] = 113)
      being evaluated for a treatment trial were studied. BDI scores were calculated
      for the complete 21-item measure as well as for the cognitive (13 items) and
      somatic (eight items) symptom subgroups. The presence of depression was
      determined using the National Institute of Mental Health Diagnostic Interview
      Schedule in accordance with the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-III-R) criteria. Receiver operating characteristic (ROC) analyses
      were used to evaluate the performance of the screening test in relation to the
      diagnostic standard. RESULTS: Depressed subjects were effectively discriminated
      from nondepressed subjects by using the full 21-item BDI, the cognitive items
      alone, or the somatic items alone (p < .001 for each comparison), although the
      cognitive items were more effective than the somatic items (p < .0005). BDI total
      scores between 12 and 14 inclusive displayed the best balance between sensitivity
      (0.90-0.82) and specificity (0.84-0.89), but a cutoff score > or = 16 for the
      entire 21-item measure exhibited the best balance between sensitivity and
      positive predictive value when prediction values were extrapolated to a diabetic
      population with a depression prevalence rate of 20%. This cutoff score would
      capture > 70% of the patients diagnosed with major depression yet provide > 70%
      certainty that a person screening positive actually has the psychiatric disorder.
      CONCLUSION: The BDI is an effective screening test for major depression in
      diabetic patients. Prospective studies are needed to confirm the test's precise
      performance characteristics in the general clinical setting.

PMID- 9021864
TI  - Physical and mental problems attributed to dental amalgam fillings: a descriptive
      study of 99 self-referred patients compared with 272 controls.
AB  - OBJECTIVE: The physical and mental symptomatology of 99 self-referred patients
      complaining of multiple somatic and mental symptoms attributed to dental amalgam
      fillings were compared with patients with known chronic medical disorders seen in
      alternative (N = 93) and ordinary (N = 99) medical family practices and patients
      with dental amalgam fillings (N = 80) seen in an ordinary dental practice.
      METHOD: The assessments included written self-reports, a 131-item somatic symptom
      checklist; Eysenck Personality Questionnaire, the General Health Questionnaire,
      and Toronto Alexithymia Scale. RESULTS: The dental amalgam sample reported
      significantly more physical symptoms from all body regions. Self-reports
      suggested that 62% suffered from a chronic anxiety disorder (generalized anxiety
      disorder or panic). Forty-seven percent suffered from a major depression compared
      with 14% in the two clinical-comparison samples and none in the dental control
      sample. Symptoms suggesting somatization disorder were found in 29% of the dental
      amalgam sample compared with only one subject in the 272 comparison subjects. One
      third of the dental amalgam patients reported symptoms of chronic fatigue
      syndrome compared with none in the dental control sample and only 2 and 6%,
      respectively, in the two clinical comparison samples. The dental amalgam group
      reported higher mean neuroticism and lower lie scores than the comparison groups.
      CONCLUSION: Self-referred patients with health complaints attributed to dental
      amalgam are a heterogeneous group of patients who suffer multiple symptoms and
      frequently have mental disorders. There is a striking similarity with the
      multiple chemical sensitivity syndrome.

PMID- 9021865
TI  - Circadian immune measures in healthy volunteers: relationship to hypothalamic
      pituitary-adrenal axis hormones and sympathetic neurotransmitters.
AB  - OBJECTIVE: The purpose of this study is to examine the circadian pattern of
      specific immunologic measures and to compare observed circadian rhythms of these
      measures with the well-established circadian rhythms of hypothalamic-pituitary
      adrenal axis hormones and sympathetic neurotransmitters. METHODS: Blood samples
      were collected every 2 hours for a total of 24 hours from nine healthy
      volunteers. The blood samples were assayed for hormones and immune measures,
      including adrenocorticotropic hormone (ACTH), cortisol, norepinephrine, and
      epinephrine. The immune measures included percentage and absolute number of
      neutrophils, lymphocytes, the lymphocyte subsets CD3+ (T cells), CD4+ (T
      helper/inducer), CD8+ (T suppressor/cytotoxic), CD56+ (natural killer [NK] cells)
      and NK cell activity (NKCA). RESULTS: The following immune measures exhibited a
      significant circadian rhythm: the percentages of neutrophils, CD4+ cells, and
      CD56+ cells; the absolute numbers of total lymphocytes, CD3+ cells, CD4+ cells,
      and CD8+ cells; and NKCA. Cross-correlations between the circadian rhythms of
      selected hormones and immune measures indicated a strong inverse association
      between the circadian rhythms of cortisol and the different T cell subsets on the
      one hand, and a strong direct association between the rhythms of cortisol and the
      percentage of CD56+ and NKCA on the other. Cross-correlations involving the
      circadian rhythms of norepinephrine and the same immune measures were in general
      much weaker and statistically nonsignificant. CONCLUSION: In healthy individuals,
      both enumerative and functional immune measures exhibit circadian rhythms that
      seem to be associated most closely with the circadian rhythm of cortisol.

PMID- 9021866
TI  - The role of stressor intensity and underlying vasculopathy in altering coronary
      reactivity in cardiomyopathic hamsters.
AB  - OBJECTIVE: Our previous work showed that stress sensitized the vessels of
      cardiomyopathic hamsters (CMHs), but only hamsters in the lesion-forming period
      of their life. We hypothesized that we would find an interaction between stressor
      intensity and microvascular vulnerability. METHOD: Male CMHs at ages of 1.5, 2.5,
      and 3.5 months were stressed with supine immobilization for five consecutive
      days. Stressor intensity was manipulated by immobilizing groups of CMHs at room
      temperature for 0 minutes, 15 minutes, 30 minutes, 1 hour, or 2 hours. CMHs were
      anesthetized and sacrificed 5 days after stress, and their hearts were perfused
      using a modified Langendorff system. Body weight changes and baseline coronary
      vascular resistance (CVR) were recorded, and CVR was also measured after coronary
      artery infusion of arginine vasopressin (AVP). RESULTS: Stress produced no effect
      on coronary vasculature in 1.5-month-old CMHs. In 2.5-month-old CMHs, only the
      two highest-intensity stressors enhanced coronary reactivity to AVP. In 3.5-month
      old CMHs, higher-intensity stressors produced a marginal AVP-induced increase in
      CVR; but this marginal increase was significantly lower than the increases seen
      with the two highest-stressor intensities in the 2.5-month-old CMHs. CONCLUSION:
      The stress-induced coronary hyperreactivity to AVP seen in 2.5-month-old CMHs
      diminished when microvascular vulnerability was lower in 3.5-month-old CMHs. For
      1.5-month-old CMHs, the resting CVR was extremely high, so that the addition of
      stress produced no further increase. Thus, stressor intensity interacted with
      microvascular vulnerability to alter the consequences of stress.

PMID- 9021867
TI  - Cognitive slowing and working memory difficulties in chronic fatigue syndrome.
AB  - OBJECTIVE: Patients with chronic fatigue syndrome (CFS) commonly report problems
      with attention, memory, learning, and speed of cognitive processing. This study
      attempted to evaluate these complaints using objective test criteria. METHOD: A
      test battery composed of six tests assessing these cognitive functions was given
      on two consecutive days. Twenty CFS patients were compared with 20 healthy
      control subjects and 14 patients with a history of major depression or dysthymia
      matched by age, intelligence, education level, and sex. RESULTS: Compared with
      control subjects, CFS patients consistently scored lower on tests in which motor
      and cognitive processing speeds were a critical factor, eg, reaction-time tasks.
      They also had more difficulty on working-memory tests in which rapid cognitive
      processing speed is also an important factor. The effort made on the first day of
      testing did not result in a decline in cognitive function on the following day.
      CFS patients did not qualify as having affective disorder by several different
      diagnostic criteria. Nonetheless, CFS patients' test performances did not differ
      from patients with a history of major depression or dysthymia. CONCLUSIONS: It is
      concluded that, although CFS and major depression and dysthymia have distinct
      clinical features, these disorders have slowed motor and cognitive processing
      speed in common.

PMID- 9021868
TI  - Globus hystericus--a somatic symptom of depression? The role of electroconvulsive
      therapy and antidepressants.
AB  - OBJECTIVE: An association of "globus hystericus" with depressive illness has
      already been established. Successful treatment with antidepressants has been
      previously reported but this is the first report of globus symptom responding to
      electroconvulsive therapy (ECT) followed by long-term remission on maintenance
      dose with tricyclic antidepressant. METHOD: A detailed retrospective study of an
      elderly patient's General Practice medical notes revealed 45-year history of
      recurrent globus symptom, interspersed with other somatic complaints. Patient's
      frequency of consultations with her family physician was noted before treatment
      and during the 5-year follow-up period. Using DSM-III diagnostic categories, the
      patient was diagnosed as suffering from major depressive disorder with globus
      symptom. The notes were insufficient to ascertain whether past episodes of globus
      occurred in a setting of depressive disorder. RESULTS: A prompt response of
      globus symptom to ECT was observed with 5-year symptom-free follow-up period as
      long as the patient remained on a maintenance dose of antidepressant. A marked
      reduction in frequency of medical consultations for other somatic complaints was
      noted. CONCLUSIONS: The case illustrates a strong association of globus symptom
      with depressive disorder and other somatic concerns. Patients with recurrent
      globus symptom and family history of depressive illness should be screened for a
      possibility of depressive disorder. ECT and antidepressants may be successfully
      used in treatment of globus in a setting of depressive illness. Long-term
      maintenance with antidepressive medication may keep at least some of these
      patients symptom-free. It is suggested that globus hystericus could be more
      appropriately viewed as a somatic symptom of depression rather than a conversion
      disorder.

PMID- 9021869
TI  - The treatment of posttraumatic stress disorder (PTSD)

PMID- 9021870
TI  - The treatment of posttraumatic stress disorder (PTSD)

PMID- 9021871
TI  - Chromatin and gene regulation at the onset of embryonic development.
AB  - Major transitions in chromosome and chromatin structure occur during development.
      Recent genetic and biochemical experiments demonstrate that these alterations in
      genome organization make significant contributions to establishing and
      maintaining states of differential transcriptional activity. Developmentally
      regulated changes in histone variants have a causal role in determining patterns
      of gene activity, directing the repression of specific eukaryotic genes.
      Chromosomal proteins such as Polycomb stabilize and maintain transcriptionally
      repressed states. Proteins regulating mitotic chromosome condensation have a role
      in determining the overall transcriptional activity of a chromosome. In this
      review, I place the developmental roles of these chromosomal constituents in a
      structural and functional context. Considerable insight now exists into the
      molecular mechanisms regulating chromosomal activity during development.
      Chromosomal architecture is emerging as a key controlling influence in the
      developmental regulation of gene expression. Recent genetic experiments using
      Caenorhabditis elegans, Drosophila melanogaster and the mouse have provided clear
      evidence for the functional differentiation of chromosomal structures during
      development. Chromosomes are visualized as highly specialized entities, within
      which the activity of particular domains is largely determined by defined
      structural proteins. At a more local level, the mechanisms regulating gene
      transcription during early embryogenesis in Xenopus and the mouse have been found
      to be dependent on the biochemical composition of individual nucleosomes. Thus,
      variation in the type and modification of chromosomal and chromatin structural
      proteins provides a dominant means of controlling the transcriptional activity of
      individual genes, individual chromosomal domains and of entire chromosomes. The
      focus of this review is to summarize these recent advances and to discuss their
      implications for developmental biology.

PMID- 9021872
TI  - Chromosomal insertion of foreign DNA.
AB  - The main route and, in most species, the only reliable route to the generation of
      transgenic animals is by microinjecting DNA into an early embryo, generally one
      of the pronuclei of a newly fertilized egg (a one-cell embryo). In most cases, a
      small number (perhaps 100) of identical cloned DNA molecules is introduced in
      this way. The weight of evidence supports the view that this DNA forms
      extrachromosomal concatemers (arrays), mainly of monomers orientated in the same
      direction, by rounds of homologous recombination. Since this occurs when a
      population of identical linear molecules is introduced, productive recombination
      can only take place after a population of circularly permuted monomers has been
      generated by circularization and random cleavage. Extrachromosomal recombination
      is known to occur by a nonconservative process in transfected mammalian cells in
      culture. Concatemeric molecules integrate into the chromosomes, more or less at
      random, by illegitimate recombination. This may occur during DNA replication,
      consistent with the very high observed frequency of transgenic founder animals
      that are mosaics of transgenic and nontransgenic cells. Foreign genes integrated
      in this way are frequently liable to chromosomal position effects, which can
      adversely affect expression. In the commercial arena this often necessitates the
      production of a large number of transgenic founders in the hope of obtaining one
      with a high expression level. Ways of approaching this practical problem are
      explored.

PMID- 9021873
TI  - Chromatin structure and gene expression in the preimplantation mammalian embryo.
AB  - The preimplantation period of mammalian development encompasses the formation of
      the zygote, the activation of the embryonic genome, the first cellular
      polarizations and the beginning of cellular differentiation. It is a period of
      transitions; protamines are replaced by histones, maternal control of development
      is succeeded by zygotic control, the highly methylated haploid parental genomes
      form a diploid genome which undergoes a wave of demethylation. It is also a
      period of manipulation of embryos for improvements in animal production; embryos
      are transferred, cryopreserved, cloned, microinjected with transgene constructs.
      This paper reviews the role that dynamic changes in chromatin structure and
      nuclear architecture play in the biological transitions of the preimplantation
      embryo. Data on the nature of these changes is presented, avenues of research
      that are opening up are discussed and potential applications in animal production
      are proposed.

PMID- 9021874
TI  - Multipoint linkage map from sperm typing data.
AB  - Sperm typing makes it possible to construct accurate multipoint linkage maps
      based on a theoretically unlimited number of meioses. The high sperm number from
      single individuals enables the dissection of hyper-recombinant regions and
      presents an ideal situation for studying recombination rate variability in
      mammals. Of particular relevance for livestock is the fact that fine structure
      mapping of functional genes by sperm typing can be used to identify the
      breakpoints between conserved syntenic groups in different species. This is
      important for the extrapolation of positional information from the highly
      developed human map to the lower density maps in farm animals.

PMID- 9021875
TI  - Moisaicism in the human preimplantation embryo.
AB  - Recent studies have revealed widespread mosaicism in the human preimplantation
      embryo at the nuclear and chromosomal level arising at fertilization and
      preimplantation development. Molecular cytogenetic analysis by fluorescent in
      situ hybridization (FISH), in particular, has for the first time made it possible
      to analyse all or almost all nuclei in cleavage stage embryos. The genotype of an
      individual is therefore not strictly defined at conception by the genotype of the
      germ cells. Rather it seems (at least in vitro) that the processes of
      fertilization, syngamy and the postzygotic mitotic divisions can be irregular. In
      some cases, therefore, the eventual genotype only emerges by a process of natural
      selection.

PMID- 9021876
TI  - The ovine callipyge locus: a paradigm illustrating the importance of non
      Mendelian genetics in livestock.
AB  - An inheritable muscular hypertrophy was recently described in sheep and shown to
      be determined by the callipyge (CLPG) gene mapped to ovine chromosome 18. We
      demonstrate in this work that the callipyge phenotype is characterized by a non
      Mendelian inheritance pattern, referred to as polar overdominance, in which only
      heterozygous individuals having inherited the CLPG mutation from their sire
      express the phenotype. The possible role of parental imprinting in the
      determinism of polar overdominance is envisaged.

PMID- 9021877
TI  - Nuclear transplantation in pigs: M-phase karyoplast to M-phase cytoplast fusion.
AB  - Porcine embryonic fibroblasts in M-phase were isolated from confluent cultures by
      selective detachment and fused to homologous metaphase II enucleated oocytes. The
      fusion products were analysed by light and electron microscopy (EM). The fusion
      treatment, per se, did not induce the disappearance of the maturation promoting
      factor (MPF) in the cloned embryos and the transferred chromatin remained
      condensed for up to 10 h. Spontaneous decondensation started after this time and,
      at about 20 h post-induction of fusion, a single large nucleus was present in the
      cytoplasm. The prolonged exposure of introduced chromatin to MPF resulted in a
      total morphological remodelling as assessed by the nucleolar morphology observed
      by EM in all the specimens.

PMID- 9021878
TI  - Immunoelectron microscope analyses of rat germinal vesicle-stage oocyte nucleolus
      like bodies.
AB  - Germinal vesicle (GV) stage oocytes isolated from rat ovaries were investigated
      by immunoelectron microscopy for the presence of several nuclear proteins in the
      prominent 'compact nucleoli' (nucleolus-like bodies named here NLB). Specific
      spliceosomal components including the Sm antigen of the nucleoplasmic small
      nuclear ribonucleoproteins (snRNP) and the non-snRNP splicing factor SC-35 were
      clearly detected in the dense finely fibrillar mass of the NLB. Moreover, the
      presence of small nuclear RNA (snRNA) in the NLB was demonstrated by means of an
      antibody which recognized the m3G-capped snRNA. The level of immunolabelling for
      the nuclear proteins fibrillarin and p80-coilin was relatively lower in the NLB.
      p80-coilin was distinctly localized, in small, poorly morphologically defined
      structural constituents in the nucleoplasm. Aggregates of intranuclear granules
      having similar antigenic composition to the NLB were also detected. Our
      observations suggested that the 'compact nucleoli' of rat GV oocytes represented
      nuclear compartments containing significant amounts of non-nucleolar,
      spliceosomal components. These NLB have a molecular composition closer to the
      composition of certain nuclear bodies than to the functional nucleoli of somatic
      cells. The NLB may represent a compartment in the mammalian oocyte, akin to the
      sphere organelle of the amphibian oocyte (also reported to contain spliceosomal
      components and a p80-coilin-related protein). Both structures may serve as
      temporary storage organelles for different maternal macromolecules, which support
      early embryonic development, inter alia of that involved in the maturation of pre
      mRNA to be transcribed from the embryonic genome.

PMID- 9021879
TI  - Isolation and characterization of maturation inhibiting compound in bovine
      follicular fluid.
AB  - The protein fraction which is responsible for the inhibition of maturation of
      bovine oocytes in vitro was isolated from cow follicular fluid by means of column
      chromatography on a Sephadex G-200 and a Sepharose 4B, both in 0.1 M ammonium
      acetate, pH 6.7. The molecular weight of the maturation inhibiting protein
      fraction is approximately 60 kDa. At a concentration of 2.0 mg/mL in cultivation
      medium, 100% of the oocytes were arrested at the germinal vesicle stage. At a
      concentration of 0.25 mg/mL, the protein fraction still had some meiosis
      inhibiting effects, but 56% of the oocytes were capable of maturing to the
      metaphase of the second meiosis (MII). Without compact cumulus the inhibiting
      fraction had no meiosis retarding effect on the oocytes. Cow follicular fluid
      also exhibited this inhibitory effect on oocyte maturation in vitro. However, the
      follicular fluid from follicles of 2.5-5.0 mm diameter showed higher meiosis
      inhibiting effects than the follicular fluid from follicles of 5-10 mm diameter.

PMID- 9021880
TI  - [Effect of weight of feature and frequency on recognition of butterfly patterns].
AB  - Three experiments are reported which deal with the nature of categorization of
      natural objects. Stimulus materials were schematic butterfly patterns. Systematic
      transformations were given to the original pattern to make stimulus instance. In
      Experiment 1, subjects were given a recognition memory task with recognition
      ratings. Recognition ratings were found to be related to family resemblance score
      (FRS: the sum of feature frequency in the category) rather than to transformation
      or subjective similarity to the original. In Experiment 2, subjects were given
      the recognition memory task while the FRS was kept constant. Weight of each
      feature affected recognition ratings differently, when FRS was kept constant. In
      Experiment 3, subjects were given the same task as in Experiment 2 while the FRS
      and the component frequency of each feature were kept constant. Again each
      feature affected recognition ratings differently. These findings suggest that
      both the frequency and weight of feature itself affect recognition ratings.

PMID- 9021882
TI  - [The estimation of the curvature of visual space with a visual triangle].
AB  - Triangular properties which Blank (1961) proposed are useful in investigating the
      geometry of visual space. With this method, however, it is not possible to
      estimate quantitatively the curvature of visual space. In the present article,
      hyperbolic and elliptic triangles are described with mathematical equations in
      the two and three dimensional Euclidean maps, and a method is proposed to
      estimate the curvature with triangular properties. Further, one experiment is
      conducted to find how the curvature changes according to the experimental
      conditions. Visual triangles are constructed in an eye level plane, a slanted
      plane and a horopter plane. The result shows that the curvature is negative in
      the eye level plane and in the slanted plane, but positive in the horopter plane.

PMID- 9021881
TI  - [An examination of support function of humor: construction of a preference scale
      for supportive humor].
AB  - In this study, we constructed a scale to measure individual preference for
      supportive humor, and examined whether the preference related to mental health.
      Two samples of female undergraduates cooperated with survey studies. In the
      first, a scale was constructed to measure preference for supportive kinds of
      humor, and relationships were examined between its score, hardiness to negative
      events, and depression, together with preference for other types of humor
      identified in a previous study (Ueno, 1992). In the second, the preference was
      correlated with hedonistic attitudes and private self-consciousness. Main
      findings were as follows: (1) Of the three types of humor (aggressive, playful,
      and supportive), only preference for supportive humor correlated with depression.
      (2) Hedonistic attitudes correlated with preference for each of the three types.
      (3) Private self-consciousness correlated only with preference for supportive
      humor.

PMID- 9021883
TI  - [On the function of swaddling as traditional infant-care practiced by Native
      South Americans].
AB  - Placing the infant in a device which restrained his/her movement was a
      traditional custom of infant caretaking in a number of parts of the world, and is
      still observed in some of them. An example of such practices, swaddling, was
      investigated with Native Americans, the Aymara, in Bolivia, and caretaking
      behaviors in 24 swaddling and 18 non-swaddling families were compared. Results
      did not support the notion that swaddling was a form of infant neglect on the
      part of caretakers. Swaddling caretakers actually exhibited as strong interest in
      the infant as non-swaddling caretakers, and spent more money on his/her clothes.
      The mother spent less time for infant care in the swaddling family. However,
      other members of the family took more time to take care of the infant than those
      in the non-swaddling family. It is argued that swaddling effectively encourages
      non-mother family members to participate in infant caretaking, in addition to
      serving a potentially beneficial function to protect infants from unsafe and
      unsanitary home environments.

PMID- 9021884
TI  - [Emotional and instrumental orientations in interpersonal attraction and their
      relationship to group norms in a group-work setting].
AB  - This study investigated the relationship between group norms and interpersonal
      attraction in group work setting. It may be assumed that interpersonal
      attraction, like group functions, has two conflictive orientations:
      instrumentality and emotionality. Relationship of the two orientations in
      interpersonal attraction to group norms was examined in two experiments. Results
      of Experiment 1, with 66 female university students, suggested that specific
      contents of group norms influenced both instrumental and emotional attraction.
      Experiment 2, with 60 female university students, indicated that emotional
      attraction had normative influence on task selection and goal setting.
      Conflicting dynamics of the two orientations in group-work setting are discussed.

PMID- 9021885
TI  - [A study on the concurrent validity of personality inventory from the view of the
      Five Factor Model concerning personality traits].
AB  - By using the Adjective Check List (ACL) in its Japanese version, the concurrent
      validity of a personality inventory is investigated through canonical correlation
      analysis and procrustes factor rotation from the view of the Five Factor Model
      concerning personality traits. After describing the objective of the present
      paper, the principles both of canonical correlation analysis and of incomplete
      orthogonal procrustes factor rotation to be used are explained. And, following
      the description concerning samples and data for analysis, the results both based
      on the scales and on the items of the personality inventory are presented. The
      important role of procrustes type of factor rotation in editing personality
      inventory is stressed before closing the discussion.

PMID- 9021886
TI  - [Independent and interdependent construal of the self: the cultural influence and
      the relations to personality traits].
AB  - The purpose of the present study was to investigate the independent and
      interdependent construal of the self in relation to the cultural difference and
      personality traits. A scale developed by Kiuchi (1995) to measure the person on
      the dimension of independent versus interdependent, the SII was administered to
      three groups of students. They were: (1) 81 college students who once lived in
      Europe or America, (2) 99 students of a college of music, and (3) 296
      undergraduates of other majors and backgrounds. Mean SII scores clearly showed
      that the first group gave the highest priority to independent construal of the
      self, the second music college group follows them, and the last group of regular
      undergraduates gave the highest priority to interdependent construal of the self.
      In addition, SII scores were shown to have significant correlations with social
      anxiety, self-monitoring, sex identity, and self-esteem. Implication of these
      results are discussed.

PMID- 9021887
TI  - [The individual difference of response to the negative side of self-enhancing
      presentation].
AB  - In this study, scales were developed to measure responses to negative aspects of
      others' and own self-enhancing presentation, and relationships among the scales
      and self-consciousness were examined. With factor analysis, the scale for
      responses to others' self-enhancing presentation was divided into three
      subscales: emotional, critical, and empathic. The scale for those of own self
      enhancing presentation was similarly divided into three: disliking, analytical,
      and accepting. The scales and self-consciousness scale (translated by Sakamoto,
      1989) were administered to 373 university and professional school students (204
      male and 169 female). The main findings were as follows: 1) Self-disliking and
      analytical subjects had high public self-consciousness and social anxiety, and
      tended to show high emotionality toward other's self-enhancing presentation. 2)
      Self-accepting subjects had high public self-consciousness, and responded
      empathically, but not emotionally, to other's self-enhancing presentation.

PMID- 9021888
TI  - [Effects of shock experience on aversiveness caused by the scream of other rats:
      overshadowing tests of the association assumption].
AB  - Distress responses of rats like screams are aversive for other rats. This study
      was conducted to determine some of the conditions affecting these aversive
      properties. Eighteen rats were trained to press a lever to obtain food on a FR4
      schedule, then assigned to Shock-experienced group (SE). Overshadow group (OS),
      and Control group (CNT). SE received three 1-second shocks (1 mA) a day for two
      days in a grid-floor box. The procedure for OS was the same as that for SE except
      that a 40-W lamp was lit 30 seconds before the onset of the shock. CNT received
      neither lights nor shocks. During the next eight days, rats received FR4 schedule
      with the same procedure as for training except that lights (40 W) or screams (65
      dB) were presented for 1 minute. When lights were presented, OS showed marked
      response suppression but SE and CNT showed little one. When screams were
      presented, SE revealed strong suppression although CNT and OS showed weak one.
      These results indicate that aversion to screams was determined by Pavlovian
      conditioning.

PMID- 9021889
TI  - [Self-acceptance as adaptively resigning the self to low self-evaluation].
AB  - In past studies, the concept of self-acceptance has often been confused with self
      evaluation or self-esteem. The purpose of this study was to distinguish these
      concepts, and operationally define self-acceptance as Carl Rogers proposed:
      feeling all right toward the self when self-evaluation was low. Self-acceptance
      as adaptive resignation, a moderating variable, therefore should raise self
      esteem of only those people with low self-evaluation. Self-acceptance was
      measured in the study as affirmative evaluation of own self-evaluation. Two
      hundred and forty college students, 120 each for men and women, completed a
      questionnaire of self-evaluative consciousness and self-esteem scales. Results of
      statistical analyses showed that among subjects with low self-evaluation, the
      higher self-acceptance, the higher the person's self-esteem. The same relation
      was not observed among those with high self-evaluation. Thus, it may be concluded
      that self-acceptance was adaptive resignation, and therefore meaningful to only
      those with low self-evaluation.

PMID- 9021890
TI  - [Social network and social support for married women and their spouses].
AB  - This study investigated various psychological aspects of social networks of
      married women and their spouses A survey data for 259 women and 185 men were
      analyzed, and main findings were as follows: 1. With marriage, support agents of
      women and men change extensively in their social networks. Wives have more
      variety in support agents within their social network, through children to their
      friends' parents. On the other hand, husbands' agents are likely to be confined
      to their wives and children. 2. Wives and husbands are similar in that their
      first choice for seeking advice is their spouse. A friend is the second choice
      for both of them. While parents, brothers and sisters serve as wives' third
      choice, there is no third for husbands. 3. Enrichment of wives' social network,
      based on a well-functioning relationship with husbands, leads to a lower degree
      of social isolation experienced by them.

PMID- 9021891
TI  - Chronic administration of the 5-HT1A receptor agonist 8-OH-DPAT differentially
      desensitizes 5-HT1A autoreceptors of the dorsal and median raphe nuclei.
AB  - The present study investigated alterations of the regulation of serotonin (5
      hydroxytryptamine; 5-HT) release by 5-HT1A autoreceptors following single and
      repeated treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n
      propylamino)-tetralin (8-OH-DPAT). Rats were pretreated with 8-OH-DPAT (1.0
      mg/kg, s.c.) for 1, 7, or 14 days. The ability of an acute challenge
      administration of 8-OH-DPAT (1.0 mg/kg, i.p.) to decrease 5-HT release in the
      ventral striatum and the ventral hippocampus of rats maintained under chloral
      hydrate anesthesia was examined 24 h after the last pretreatment injection using
      in vivo microdialysis. The decrease of 5-HT release in the striatum produced by
      the challenge dose of the 5-HT1A receptor agonist was diminished following 7 and
      14 days of pretreatment, but not after 1 day of pretreatment, with 8-OH-DPAT. In
      contrast, decreases of 5-HT release in the hippocampus by the 8-OH-DPAT challenge
      were not altered after 1 or 7 days of pretreatment, and only a trend for
      attenuation appeared after pretreatment for 14 days. The results of the present
      study indicate that desensitization of 5-HT1A autoreceptors regulating 5-HT
      release in different brain regions by repeated treatment with 8-OH-DPAT occurs at
      different rates.

PMID- 9021892
TI  - Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein
      partially purified from rat liver and rat brain membranes: an opioid/sigma
      receptor?
AB  - A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was
      partially purified from rat liver and rat brain membranes in an affinity
      chromatography originally designed to purify sigma receptors. Detergent
      solubilized extracts from membranes were adsorbed to Sephadex G-25 resin
      containing an affinity ligand for sigma receptors: N-(2- 3,4
      dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE).
      After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047
      was detected in the eluates. However, the protein was not the sigma receptor.
      [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds
      in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/
      )cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (
      )SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o
      tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein.
      Tryptic digestion and heat treatment of the affinity-purified protein abolished
      radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis
      (SDS/PAGE) of the partially-purified protein from the liver revealed a major
      diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and
      another polypeptide of > 97 kDa. This study demonstrates the existence of a novel
      protein in the rat liver and rat brain which binds opioids, benzomorphans, and
      haloperidol with namomolar affinity. The protein resembles the opioid/sigma
      receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther.,
      197:517-532.]. A high degree of purification of this protein has been achieved in
      the present study.

PMID- 9021893
TI  - Depression of early and late monosynaptic inhibitory postsynaptic potentials in
      hippocampal CA1 neurons following prolonged benzodiazepine administration: role
      of a reduction in Cl- driving force.
AB  - GABAergic synaptic responses were studied by direct, monosynaptic activation of
      GABAergic interneurons in the CA1 region of in vitro hippocampal slices from rats
      made tolerant to the benzodiazepine, flurazepam. Monosynaptic IPSPs were elicited
      in CA1 pyramidal neurons, following 1 week oral flurazepam administration, by
      electrical stimulation at the stratum oriens/stratum pyramidale or stratum
      radiatum/ stratum-lacanosum border < or = 0.5 mm from the recording electrode
      plane. Excitatory input to pyramidal cells and interneurons was eliminated by
      prior superfusion of the glutamate receptor antagonists, APV (50 microM) and DNQX
      (10 microM). GABAA receptor-mediated early IPSPs were further isolated by
      perfusion of the GABAB antagonist, CGP 35348 (25 microM) or by diffusion of Cs-
      from the recording electrode. GABAB receptor-mediated late IPSPs were
      pharmacologically isolated by perfusion of the GABAA antagonist, picrotoxin (50
      microM). There was a significant decrease in the amplitude of pharmacologically
      isolated early and late IPSPs in FZP-treated neurons without a change in passive
      membrane properties. A shift of the early IPSP, but not the late IPSP, reversal
      potential in FZP-treated neurons suggested that a change in the driving force for
      anions, presumably Cl, in CA1 neurons was one important factor related to the
      decreased early IPSP amplitude after prolonged activation of GABAA receptors by
      flurazepam. A decreased early IPSP amplitude accompanied by a decreased late IPSP
      amplitude suggested that presynaptic GABA release onto FZP-treated pyramidal
      cells may also be reduced. We conclude from these data that an impairment of
      GABAergic transmission in CA1 pyramidal neurons associated with the development
      of tolerance during chronic benzodiazepine treatment may be related to the
      regulation of both pre- and postsynaptic mechanisms at the GABA synapse.

PMID- 9021894
TI  - Dopamine D2-like sites in schizophrenia, but not in Alzheimer's, Huntington's, or
      control brains, for [3H]benzquinoline.
AB  - Although the basis of schizophrenia is not known, evidence indicates a possible
      overactivity of dopamine pathways. In order to detect any new dopamine receptor
      like sites which may be altered in schizophrenia, the present study used a new
      radioligand, a [3H]benzo[g]quinoline. The receptors were labelled by this ligand
      in the presence of other drugs to block the known dopamine D1, D2, D3, or D5
      receptors (no D4-selective ligands are available to block D4). Using this method,
      we found that schizophrenia brain striata had elevated levels of a D2-like site
      not detected in control human postmortem brains or in Alzheimer's, Huntington's,
      or Parkinson's disease brains. The ligand acted as an agonist at this D2-like
      site, because binding was abolished by guanine nucleotide. The binding of the
      ligand to the D4 receptor, however, was not sensitive to guanine nucleotide. The
      site differed from D2 itself, because S- and R-sulpiride were equally potent at
      the D2-like site. The D2-like sites were present in rat and mouse brain but were
      absent in brain slices from transgenic mice where D2 had been knocked out. The
      abundance of the receptor was not related to premortem use of antipsychotic
      drugs. Future research should examine the biochemical differences between the D2
      dopamine receptor and these D2-like sites in schizophrenia.

PMID- 9021895
TI  - P-[18F]-MPPF: a potential radioligand for PET studies of 5-HT1A receptors in
      humans.
AB  - The purpose of this study was to develop a radiopharmaceutical that could be used
      to selectively image 5-HT1A receptors with positron emission tomography (PET). No
      carrier-added 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[18F]
      fluorobenzamido]ethylpiperazine (p-[18F]-MPPF, 2) was synthesized by the
      nucleophilic substitution of the corresponding nitro precursor 1 with
      K[18F]/Kryptofix 2.2.2. in dimethyl sulfoxide (DMSO) at 140 degrees C for 20 min
      followed by purification with high-performance liquid chromatography (HPLC) in
      10% yield in a synthesis time of 90 min from end of bombardment (EOB). Specific
      activity was 1-4 Ci/microM. Biodistribution studies in rats showed that the
      initial uptake of 2 in the brain was high (0.7% dose/g tissue at 2 min). It was
      then rapidly eliminated. Rates of elimination were significantly slower in brain
      regions with high concentrations of 5-HT1A receptors (hippocampus, cortex, and
      hypothalamus) than in control regions. The maximum hippocampal/cerebellar ratio
      was 5.6:1 at 30 min postinjection. Uptake values in serotonergic, but not in
      control, regions were significantly reduced by prior treatment with either (+/-)
      8-OH-DPAT (2 mg/kg, i.v., 5 min prior) or WAY 100635 (1 mg/kg, i.v., 5 min
      prior). Radioactivity in the femur did not increase with time, suggesting that in
      vivo defluorination may not be the major route of metabol sm. PET studies of 2 in
      a monkey demonstrated selective uptake and retention of 2 in the hippocampus. The
      hippocampal/cerebellar ratio was 3:1 at 30 min postinjection. The ratio was
      reduced to 1:1 by administering (+/-)-8-OH-DPAT (2 mg/kg, i.v.) 23 min
      postinjection of 2. Analyses of arterial plasma by HPLC revealed that 20% of
      radioactivity in the plasma remained as the parent compound 2 at 30 min
      postinjection. The results suggest that p-[18F]-MPPF may be a useful radioligand
      for studying cerebral 5-HT1A receptors in humans with PET techniques.

PMID- 9021896
TI  - Binding of the [125I]3 beta-(iodophenyl)tropan-2 beta-carboxylic acid isopropyl
      ester to the dopamine transporter at a physiologically relevant temperature:
      mutually exclusive binding and different ionic requirements for various uptake
      blockers and substrates.
AB  - The present study describes the binding of cocaine analog [125I]3 beta
      (iodophenyl)tropan-2 beta-carboxylic acid isopropyl ester ([125I]RTI-121), a
      highly selective ligand for the dopamine transporter (DAT), to rat striatal
      synaptosomal membranes at 37 degrees C. Saturation analysis of [125I]RTI-121
      binding revealed a single binding site with similar affinity for RTI-121 at both
      50 and 134 mM NaCl. However, the density of binding sites was reduced at 134 mM
      NaCl. Various uptake blockers and substrates of the DAT monophasically inhibited
      the specific binding of [125I]RTI-121. Increasing the NaCl concentration from 50
      mM to 134 mM enhanced the affinity of the substrate dopamine and amphetamine for
      the DAT, without affecting that of the uptake blockers. At 134 mM NaCl, the
      copresence of GBR12935, BTCP, cocaine, amphetamine, or dopamine decreased the
      affinity of RTI-121 to the extent predicted by a model in which the binding of
      all compounds is mutually exclusive. This, along with a different NaCl
      sensitivity for blockers and substrates, suggests that the two categories of
      compounds recognize nonidentical but overlapping binding domains on the DAT. In
      contrast, the mutually exclusive binding with similar NaCl sensitivity for RTI
      121 and the other uptake blockers tested here suggests the involvement of common
      binding domains in the recognition of these blockers.

PMID- 9021897
TI  - Comparative evaluation of [3H]WIN 35428 and [3H]GBR 12935 as markers of dopamine
      innervation density in brain.
AB  - WIN 35428 and GBR 12935, two uptake blocker ligands of the membrane transporter
      for dopamine (DA), were evaluated as quantitative markers of DA innervation
      density in CNS tissue. From alternate rat brain slices respectively processed for
      either light microscope or film autoradiography, counts of DA axon terminals
      (varicosities) labeled by uptake/storage of [3H]DA were matched with
      densitometric measurements of the specific binding of [3H]WIN 35428 and [3H]GBR
      12935 in the same anatomical areas. The relation between the two parameters was
      examined in 1) the normal cingulate cortex; 2) the neostriatum severely DA
      denervated by unilateral intramesencephalic injections of 6-hydroxydopamine; and
      3) the neostriatum, partly DA-reinnervated by an intrastriatal graft of fetal
      mesencephalic neurons after prior 6-hydroxydopamine lesion. For technical
      reasons, the hyperdense DA innervation of normal striatum was not amenable to
      such correlative testing. Data were subjected to multilevel analysis. Specific
      [3H]WIN binding at 37 degrees C was tightly and linearly correlated with the
      number of DA varicosities over the full range of DA innervation densities tested.
      The regression lines for intact cortex and for DA-denervated as well as DA
      reinnervated neostriatum had the same slope and crossed the ordinate near zero.
      In contrast, [3H]GBR 12935 binding at 37 degrees C showed no correlation with the
      number of DA varicosities. A linear correlation could be obtained after
      incubation with [3H]GBR 12935 at 4 degrees C in the presence of ZnSO4, but the
      intercept of this regression line remained significantly above zero at origin,
      indicating extraneous binding to non-DA transporter sites. Providing that the
      hyperdense DA innervation of the normal neostriatum does not generate a
      particular problem in vivo as it does in vitro. WIN 35428, but not GBR 12935,
      might satisfy the selectivity and sensitivity requirements of a quantitative
      marker of DA innervation density for eventual use in positron emission
      tomographic studies.

PMID- 9021898
TI  - Methamphetamine induces apoptosis in immortalized neural cells: protection by the
      proto-oncogene, bcl-2.
AB  - Methamphetamine (METH) is an amphetamine analog that produces degeneration of the
      dopaminergic system in mammals. The neurotoxic effects of the drug are thought to
      be mediated by oxygen-based free radicals. In the present report, we have used
      immortalized neural cells obtained from rat mesencephalon in order to further
      assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested
      if the anti-death proto-oncogene, bcl-2 could protect against METH-induced
      cytotoxicity. METH caused dose-dependent loss of cellular viability in control
      cells while bcl-2-expressing cells were protected against these deleterious
      effects. Using flow cytometry, immunofluorescent staining, and DNA
      electrophoresis, we also show that METH exposure can cause DNA strand breaks,
      chromatin condensation, nuclear fragmentation, and DNA laddering. All these
      changes were prevented by bcl-2 expression. These observations provide further
      support for the involvement of oxidative stress in the toxic effects of
      amphetamine analogs. They also document that METH-induced cytotoxicity is
      secondary to apoptosis. These findings may be of relevance to the cause(s) of
      Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic
      pathway.

PMID- 9021899
TI  - Dopamine selects glutamatergic inputs to neostriatal neurons.
AB  - Glutamatergic synaptic potentials induced by micromolar concentrations of the
      potassium conductance blocker 4-aminopyridine (4-AP) were recorded
      intracellularly from rat neostriatal neurons in the presence of 10 microM
      bicuculline (BIC). These synaptic potentials originate from neostriatal cortical
      and thalamic afferents and were completely blocked by 10 microM 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) plus 100 microM D-2-amino-5-phosphonovaleric
      acid (2-APV). Their inter-event time intervals could be fitted to exponential
      distributions, suggesting that they are induced randomly. Their amplitude
      distributions had most counts around 1 mV and fewer counts with values up to 5
      mV. Since input resistance of the recorded neurons is about 40 M omega, the
      amplitudes agree to quantal size measurements in mammalian central neurons. The
      action of a D2 agonist, quinpirole, was studied on the frequency of these events.
      Mean amplitude of synaptic potentials was preserved in the presence of 2-10
      microM quinpirole, but the frequency of 4-AP-induced glutamatergic synaptic
      potentials was reduced in 35% of cases. The effect was blocked by the D2
      antagonist sulpiride (10 microM). Input resistance, membrane potential, or firing
      threshold did not change during quinpirole effect, suggesting a presynaptic site
      of action for quinpirole in some but not all glutamatergic afferents that make
      contact on a single cell. The present experiments show that dopaminergic
      presynaptic modulation of glutamatergic transmission in the neostriatum does not
      affect all stimulated afferents, suggesting that it is selective towards some of
      them. This may control the quality and quantity of afferent flow upon neostriatal
      neurons.

PMID- 9021900
TI  - Effect of the acute and chronic administration of the selective neurokinin2
      receptor antagonist SR 48968 on midbrain dopamine neurons in the rat: an in vivo
      extracellular single cell study.
AB  - In this study, we examined the effect of the acute and chronic administration of
      the selective neurokinin2 (NK2) receptor antagonist SR 48968 on the activity of
      spontaneously active dopamine (DA) cells in the substantia nigra pars compacta
      (SNC) and ventral tegmental area (VTA) in anesthetized, male rats. This was
      accomplished using the technique of in vivo, extracellular single cell recording.
      The intravenous (i.v.) administration of SR 48968 (10-1280 micrograms/kg) did not
      significantly alter the basal firing rate or pattern of either spontaneously
      active SNC or VTA DA neurons compared to control. However, the acute
      administration of 1 mg/kg, i.p., of SR 48968, but not its inactive enantiomer SR
      48965, produced a significant increase in the number of spontaneously active DA
      cells in the SNC (48%) and VTA (28%) compared to vehicle controls. The i.p.
      administration of SR 48968 did not alter the basal firing pattern of either SNC
      or VTA DA neurons compared to vehicle controls. The pretreatment of animals with
      1 mg/kg, i.p., of SR 48968 significantly potentiated the suppressant action of
      (+)-apomorphine on spontaneously active SNC and VTA DA cells. In contrast to its
      acute effects, the administration of 1 mg/kg, i.p. of SR 48968 once daily for 21
      days produced a significant decrease in the number of spontaneously active DA
      cells in the SNC and VTA. The decrease in the number of spontaneously active VTA
      DA cells was not reversed by (+)-apomorphine administration in fact, a further
      decrease in the number of VTA DA cells was observed. This suggests that the SR
      48968-induced decrease in the number of spontaneously active DA neurons may not
      be the result of depolarization block. Overall, these results suggest that the
      acute and chronic administration of SR 48968 alters the number of spontaneously
      active midbrain DA neurons in anesthetized rats.

PMID- 9021901
TI  - Expression of D1 receptor mRNA in projections from the forebrain to the ventral
      tegmental area.
AB  - In situ hybridization was combined with Fluoro-Gold retrograde labeling to
      determine if cells projecting from the forebrain to the ventral tegmental area
      (VTA) express D1 receptor mRNA. Cell counts were made in the prefrontal cortex,
      shell of the nucleus accumbens, and ventral pallidum to estimate the percentage
      of neurons projecting to the VTA that express D1 receptor mRNA. Retrogradely
      labeled cells were observed in the infralimbic and prelimbic regions of the
      prefrontal cortex, and up to 37% of the retrogradely labeled cells expressed D1
      receptor mRNA. Double-labeled cells constituted up to 89% of retrogradely labeled
      neurons in the rostral shell and up to 68% in the caudal shell of the nucleus
      accumbens. The number of retrogradely labeled cells in the ventral pallidum that
      were double-labeled ranged from 13% in the rostral to less than 10% in the caudal
      portions. These data provide anatomical support for a role of D1 receptors in the
      reciprocal innervation between the forebrain and VTA.

PMID- 9021902
TI  - Inhibition of dopamine re-uptake: significance for nigral dopamine neuron
      activity.
AB  - In the present study the effect of inhibition of the re-uptake of dopamine (DA)
      was analysed with respect to DA release and to the firing pattern of DA neurons
      in the substantia nigra (SN). Intravenous administration of GBR 12909 (0.5-8
      mg/kg), a specific and potent inhibitor of DA re-uptake, was found to dose
      dependently increase the DA concentration both in the SN and in the striatum, as
      measured by microdialysis. However, the drug failed to significantly affect the
      firing rate of the nigral DA neurons. In contrast, GBR 12909 dose-dependently
      induced a regularisation of the firing pattern, concomitant with a reduction in
      burst activity. An acute hemisection of the brain, which by itself produced a
      slight regularisation of the firing pattern of the nigral DA neurons without
      changing the firing rate of the ability of the DA neurons to fire in bursts, was
      found to prevent the regulatory action of GBR 12909. Pretreatment with the
      selective GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v., 5 min) did not
      significantly affect the firing rate, the regularity of the DA neurons, or their
      ability to fire in bursts. However, CGP 35348 markedly antagonised the ability of
      GBR 12909 to induce pacemaker-like firing or a decrease in burst activity of the
      nigral DA neurons. The results of the present study suggest that a striatonigral
      feedback projection may serve to control the activity of nigral DA neurons not
      primarily by regulating the firing rate, but, preferably, by modulating the
      firing pattern of the neurons. In this regard, activation of somatodendritic
      GABAB-receptors may form the final link in this feedback inhibitory control
      system.

PMID- 9021903
TI  - Do long-term results justify bridging to heart transplantation in patients with
      multi-organ dysfunction?
AB  - This retrospective study was performed to determine the influence of multi-organ
      dysfunction and the type of preoperative hemodynamic support on mortality after
      heart transplantation. All patients undergoing heart transplantation during a 6
      year period were divided into 3 groups: group A patients (n = 110) had stable
      hemodynamics on oral medication, group B recipients (n = 41) received continuous
      i.v. catecholamine application, and in group C (n = 21) mechanical hemodynamic
      support was necessary. In groups B and C elevated serum creatinine and
      transaminase levels-reflecting renal and hepatic dysfunction-were detected more
      often and the survival rate was worse during the first six months (A: 85%, B:
      71%, C: 52%, p < 0.01). In group C the prognosis of patients with multi-organ
      dysfunction was significantly worse compared to patients with normal renal and
      hepatic function (38% vs. 75%; p < 0.01). In recipients surviving for six months,
      there was no difference in long-term prognosis between the groups studied. It is
      concluded that heart transplantation in patients with multi-organ dysfunction on
      invasive hemodynamic support bears a significantly increased risk in the early
      postoperative period. In view of the current donor shortage the condition of
      other organs should be improved before transplantation as far as possible, even
      using long-term mechanical support.

PMID- 9021904
TI  - Heart transplantation in patients with diabetic end-organ damage before
      transplantation.
AB  - Diabetes mellitus with preexisting end-organ damage (EOD) is considered a
      contraindication for heart transplantation. The outcome of such patients has not
      been well characterized. Among 138 patients transplanted between 12/88 and 7/94,
      29 were diabetic (11 insulin-dependent); of these, 12 had preexisting EOD,
      defined as a creatinine clearance < or = 50 ml/min, a 24-hour urine protein
      concentration > or = 500 mg/L or typical symptoms of peripheral or autonomic
      polyneuropathy, and 17 had no EOD. We compared diabetics with and without EOD and
      non-diabetics (n = 109) for operative mortality, length of stay, serum
      creatinine, fasting glucose levels, and postoperative prednisone doses at 1,6,
      and 12 months. Actuarial survival and freedom from rejection and infection were
      analyzed. Both diabetic groups were significantly older than nondiabetics,
      Ischemic time, operative mortality, surgical technique, ICU- and total length of
      stay were similar. Actuarial survival and freedom from rejection were similar
      among the three groups. Infection rates including CMV did not differ. Serum
      creatinine levels increased in all groups compared to pretransplant levels (p =
      0.001), but without significant differences among the groups. Post-transplant
      glucose levels at 6 and 12 months were higher for diabetic patients with EOD than
      for those without or for nondiabetics (183, 153, and 94 mg/dl at 6 months, p =
      0.01; 202, 161, and 102 mg/dl at 12 months, p = 0.0001). Prednisone dosage was
      lower in diabetics with EOD at 6 months, but did not differ among the three
      groups at 12 months. The incidence of angiographically proven transplant
      vasculopathy did not differ at 1 and 2 years. Diabetics with preexisting EOD
      undergoing heart transplantation experience similar short- and intermediate-term
      results when compared to diabetics without EOD and nondiabetics. Metabolic
      control is more difficult to achieve, as indicated by higher fasting glucose
      levels. Larger and longer-term prospective studies have to confirm our findings,
      since the shortage of donor organs would increase if such patients were
      transplanted routinely.

PMID- 9021905
TI  - Mortality and worsening of prognostic profile during waiting time for valve
      replacement in aortic stenosis.
AB  - In a prospective study 99 consecutive patients with operative indication due to
      severe aortic stenosis (AS) were put on a surgical waiting list. The waiting-time
      to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There were
      58 men and 41 women with a mean age of 61 years (21-82 years). The patients were
      divided into three groups: group I (n = 81) with an uneventful stay on the
      waiting list (including one patient who declined the AVR offer); group II (n =
      11) with significant worsening of a prognostic index; and group III (n = 7) with
      patients who died during the waiting-time. The waiting-list death rate was 13.5
      +/- 5.0% patient-year-1 compared with a post-AVR death rate of 4.9 +/- 0.9%.
      patient-year-1 (p < 0.05) with a mean post-AVR follow-up of 5.7 years. According
      to their prognostic index at inclusion, group II patients had a predicted (by a
      Cox model) 7-year post-AVR survival probability of 72%, but only of 61% according
      to their prognostic index immediately preoperatively; their observed 7-year post
      AVR survival was 60%. Logistic regression analysis identified high age, short
      duration of symptoms, severe hypertrophy and strain in the ECG, female sex, and
      deranged left-ventricular diastolic function (related to severely increased left
      ventricular muscle mass) as independent predictors of death on the waiting-list
      and prognosis worsening. From a clinical viewpoint, the predictive models did not
      allow sufficiently accurate identification of the patients at risk during the
      waiting-time. The consequences of a surgical waiting-time averaging 6 months are
      serious for AS patients. The death rate is high and a subgroup worsen their
      prognostic profile, with significantly reduced post-AVR long-term survival as the
      result.

PMID- 9021906
TI  - Postoperative changes in myosin light chain and comparison with postoperative
      clinical variables in patients who have undergone valve surgery.
AB  - We measured the levels of creatine kinase-MB (CK-MB) and myosin light chain
      (MLCI) in 86 patients after double valve replacement to investigate whether
      measurement of the postoperative changes in myosin could be useful in patients
      undergoing valve surgery. In particular, we compared the postoperative levels of
      CK-MB and MLCI with the occurrence of postoperative low cardiac output syndrome
      (LOS). In both groups of patients (group I: without LOS, group II: with LOS), the
      peak CK-MB level was observed on postoperative day 1, and the peak myosin level
      on postoperative day 5. No significant differences were found in the
      postoperative levels of CK-MB between the two groups. On the other hand, a
      significant difference in the levels of MLCI on postoperative day 5 was observed
      (p < 0.05). Our results also showed that the peak level of CK-MB significantly
      correlated with the cardiopulmonary bypass time (r = 0.50), while the peak level
      of MLCI was significantly correlated with the postoperative cardiac index (r = 
      0.45). Our retrospective findings suggest that postoperative measurement of MLCI
      may be useful for estimating the postoperative myocardial impairment after valve
      surgery.

PMID- 9021908
TI  - The prevalence of lung cancer in vascular surgery patients.
AB  - Inhalative cigarette smoking is a major risk factor for atherosclerotic disease
      as well as primary carcinoma of the lung. On that account, this study was
      performed to determine the prevalence of primary lung cancer on admission in
      patients scheduled for vascular surgery. All patients presenting to our
      department for an intervention are screened for lung diseases. If this
      pretherapeutic examination suggests the existence of a lung tumor further
      diagnostic procedures are performed. Making use of a prospective computer
      assisted patient-documentation system, we analysed incidental findings of lung
      cancer in those patients admitted for elective surgery. Between Jan. 1st 1990 and
      October 31st 1994, we electively treated 2214 patients with the diagnosis of
      vascular stenosis (n = 1711/77.3%) or atherosclerotic aneurysms (n = 503/22.7%)
      in our department. In 16 of these patients (m:f = 13:3; age 50-72 [mean: 61.1]
      years) a carcinoma of the lung was detected during preoperative diagnostic
      procedures, a prevalence of 0.72%. All these patients were smokers, with a daily
      inhalative nicotine consumption averaging 25 cigarettes per day for a mean of 35
      years. 8 patients underwent a surgical (n = 6) or other invasive (n = 2) vascular
      interventions. In 8 patients no vascular intervention was performed because of
      the revealed lung carcinoma. The prevalence of lung cancer in a population of
      vascular patients in the present study is in accord with data of older
      investigations of high-risk groups. Only 2 out of 16 lung cancers were detected
      at a prognostically favourable stage. Smokers with symptoms of vascular disease
      should be carefully examined for signs of lung cancer.

PMID- 9021907
TI  - Prevention of atrial tachyarrhythmias after non-cardiac thoracic surgery by
      infusion of magnesium sulfate.
AB  - The possible role of magnesium sulfate (MgSO4) infusion in the prevention of
      atrial tachyarrhythmias after non-cardiac thoracic surgery was evaluated through
      a prospective study of two hundred patients who underwent non-cardiac thoracic
      surgery. The patients (who fulfilled the following requirements among others: no
      myocardial infarction in the previous six months, normal renal function, no use
      of digitalis or antiarrhythmic drugs, not undergone emergency operations or video
      assisted thoracic surgery), were randomly assigned to receive MgSO4 infusion in
      all circumstances (Mg group), or either no treatment or, if aged over 70 or in
      cases of pneumonectomy or an intrapericardial procedure, application of digoxin
      starting on the day of operation (control group). 95 patients were enrolled in
      the Mg group and 105 in the control group. 93 patients in the Mg group and 101 in
      the control group were evaluated. Post-operative atrial tachyarrhythmias, mainly
      atrial fibrillation, occurred in 10 patients (10.7%) in the Mg group and in 27
      (26.7%) patients in the control group (chi 2 = 7.009, df = 1. p = 0.008). It is
      concluded that infusion of MgSO4 is an effective means of reducing the incidence
      of atrial tachyarrhythmias after non-cardiac thoracic surgery.

PMID- 9021909
TI  - Open window thoracostomy in the treatment of esophageal or bronchopleural fistula
      with advanced mediastinitis and septic shock.
AB  - Mediastinitis and septic shock following esophageal or bronchopleural fistula are
      rare but serious conditions with a high mortality rate. Six patients were treated
      with open window thoracostomy (OWT) after primary suture repair and closed tube
      drainage had failed to cure the patient's condition. In all cases the clinical
      condition improved immediately. Two patients died later because of unrelated
      diseases. OWT should be considered in critically ill patients with broncho- or
      esophagopleural fistula when primary therapy fails to control the septic focus.

PMID- 9021910
TI  - Pericardiectomy for constrictive pericarditis using a percutaneous heparin-coated
      cardiopulmonary support system.
AB  - We report a case in which a percutaneous heparin-coated cardiopulmonary support
      system enabled a safe and effective pericardiectomy to be performed. It was
      employed when severe hypotension suddenly arose during the operation to treat
      constrictive pericarditis.

PMID- 9021911
TI  - Mitral insufficiency caused by systemic lupus erythematosus requiring valve
      replacement: three case reports and a review of the literature.
AB  - The increase of mitral valve insufficiency associated with systemic lupus
      erythematosus (SLE) seems to be related to the treatment with corticosteroids.
      Corticosteroids heal Libman-Sacks endocarditis, but thereby they lead to
      fibrotic, retracted leaflet tissue and thus to severe valvular dysfunction. We
      present three patients with SLE who underwent mitral valve replacement due to
      severe mitral insufficiency. All had been treated with corticosteroids for
      several years prior to the surgical intervention. Macroscopic and microscopic
      examination of the valves revealed no active endocarditis. Instead, fibrotic,
      retracted, and calcified valve leaflets could be observed in two cases, and
      ballooned and fibrotic leaflets in the third case. We compare our patients to 25
      cases with SLE reported in the literature so far, who also had to be submitted to
      mitral valve replacement. Postoperative outcome was uneventful in most cases and
      allows surgical intervention to be considered as a feasible treatment without
      major risk in patients with compensated organ function.

PMID- 9021912
TI  - Primary sternal tuberculosis treated by resection and reconstruction.
AB  - We report a case of primary mycobacterial sternal infection. An 81-year-old man
      with an infected parasternal sinus of non-specific pathology was treated with
      antibiotics for four months with only palliative effect. On hospital admission CT
      scan showed thickened first and second intercostal spaces and chest wall, but no
      bone involvement. At operation, the manubrium was found to be infected also. This
      was excised with the first three ribs anteriorly. Histology showed caseating
      granulomata. No other tuberculous foci were found in the patient.

PMID- 9021913
TI  - A case of malignant Triton tumor of the lung.
AB  - The present paper reports a 28-year-old male with an asymptomaticmalignant Triton
      tumor of the lung. Chest radiographs revealed a mass in the left hilum. The left
      lower lobe including the tumor and the mediastinal lymph node was resected. There
      was no metastasis or tumor recurrence during the one-year period following the
      surgical procedure. To our knowledge, this is the first case report of a primary
      pulmonary malignant Triton tumor.

PMID- 9021914
TI  - A case of malignant fibrous histiocytoma of the lung arising as a third primary
      tumor.
AB  - A case of primary malignant myxoid fibrous histiocytoma of the lung presenting as
      a solitary lung nodule in a 61-year-old man is presented. This tumor arose in a
      patient with a transitional-cell carcinoma of the urinary bladder and a well
      differentiated squamous-cell carcinoma of the larynx. The differential diagnosis
      between a primary lung tumor, versus a solitary metastasis is difficult and was
      supported by histological features and the lack of epithelial properties proved
      by immunohistochemistry. Tobacco was the only etiologic factor known in the
      patient.

PMID- 9021915
TI  - Intercostal hemangioma.
AB  - Chest wall tumors are uncommon and there have been only a few reports of
      intercostal hemangioma during the past 20 years. We treated a 33-year-old man who
      presented with intercostal hemangioma. We resected tumor and surrounding muscles
      beyond the limits of the lesion without removing any bone or lung tissue. The
      patient is free of any recurrence 3 years after surgery.

PMID- 9021916
TI  - Enhancement of immune response to naked DNA vaccine by immunization with
      transfected dendritic cells.
AB  - Immunization with plasmid DNA encoding various proteins promises to be a valuable
      vaccine approach especially if its immunogenicity could be optimized. In this
      study we show that the intramuscular delivery in dendritic cells (DC) of naked
      plasmid DNA encoding two proteins of herpes simplex virus (HSV) leads to the
      induction of significantly enhanced levels of resistance to viral challenge.
      Whereas DC transfected in vitro with DNA induced enhanced immunity, similarly
      transfected macrophage (M phi) populations lacked immunogenicity even though
      plasmid expression occurred in vitro. The enhanced immunity induced by DC
      delivered DNA appeared to be associated mainly with an increased Th1 CD4+ T cell
      response. Our results add evidence that DC are the essential antigen-presenting
      cell types involved in immune responses to intramuscularly administered DNA
      vaccines.

PMID- 9021917
TI  - Marked inhibition of the intracellular multiplication of Legionella pneumophila
      in monocytes isolated from carriers of human T lymphotrophic virus type I.
AB  - Intracellular growth patterns of Legionella pneumophila were examined in
      monocytes obtained from carriers of human T-lymphotropic virus type I (HTLV-1)
      and controls who were HTLV-1 seronegative. All subjects were seronegative for
      antibodies against L. pneumophila. Bacterial growth was determined 0, 1, 2,
      and/or 3 days after infecting peripheral blood mononuclear cells (PBMCs) with the
      bacteria. The intracellular growth of L. pneumophila was markedly inhibited in
      HTLV-1 carriers compared with normal controls. When the lymphocytes were depleted
      from the HTLV-1 carrier PBMC cultures before infection, this inhibition was
      abolished. Inhibition reappeared, however, when the 72-h culture supernatants of
      PBMCs from HTLV-1 carriers were added to the lymphocyte-depleted cultures.
      Culture supernatants of infected and uninfected PBMCs from HTLV-1 carriers
      exhibited markedly increased levels of interferon-gamma (IFN-gamma) and tumor
      necrosis factor alpha (TNF-alpha) compared with the HTLV-1 seronegative controls.
      In the HTLV-1 carriers, IFN-gamma was produced by the CD4+ lymphocytes, whereas
      TNF-alpha was secreted by the monocytes. Addition of anti-IFN-gamma or anti-TNF
      alpha antibodies to the HTLV-1 carrier PBMC cultures diminished the inhibition of
      intracellular growth of L. pneumophila. Results suggest that the monocytes are
      activated in HTLV-1 carriers. These findings may explain why an opportunistic
      infection by certain intracellular pathogens is rarely seen among HTLV-1
      carriers.

PMID- 9021918
TI  - IgM-mediated opsonization and cytotoxicity in the shark.
AB  - Two types of cytotoxic reactions have been observed using cells from the nurse
      shark: spontaneous cytotoxicity mediated by cells of the macrophage lineage and
      antibody-dependent killing carried out by a different effector cell population.
      Previous data showed that removal of phagocytic cells using iron particles
      abolished macrophage-mediated killing, but not antibody-dependent reactions. The
      current study used single cell assays and showed that the effector of antibody
      driven reactions was the neutrophil. Surprisingly, the mechanism of killing was
      shown to be phagocytosis mediated by both 7S and 19S immunoglobulin M (IgM).
      Reactions proceeded with as little as 0.01 microg of purified 19S or 7S IgM and
      were complete within 4-6 h. In contrast, purified immunoglobulin did not adsorb
      to macrophages and had no effect on target cell binding or cytotoxicity.
      Pretreatment of cells with cytochalasin D abolished the phagocytic reaction, but
      not spontaneous cytotoxicity. These data show that antibody-mediated killing
      results from opsonization and phagocytosis; the mechanism of macrophage killing
      is currently unknown. In addition, these data show that the shark neutrophil, not
      the macrophage lineage, carries a receptor for Fc mu.

PMID- 9021919
TI  - MIP-1 alpha contributes to the anticryptococcal delayed-type hypersensitivity
      reaction and protection against Cryptococcus neoformans.
AB  - Leukocyte infiltration into infected tissues is essential for the clearance of
      microorganisms. In animals with a cell-mediated immune (CMI) response to the
      infectious agent, as opposed to naive animals, leukocyte migration is greatly
      enhanced into sites of the organism or antigen. The role of the,chemotactic
      cytokine or chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), in
      the expression phase of the CMI response and in protection against Cryptococcus
      neoformans was assessed. With the use of a gelatin sponge model in mice as a
      means of detecting an anti-cryptococcal delayed-type hypersensitivity (DTH)
      reaction, we found that MIP-1 alpha levels in fluids from cryptococcal antigen
      (CneF)-injected sponges in immunized mice (DTH-reactive sponges) were
      significantly increased over levels of MIP-1 alpha in fluids from saline-injected
      control sponges at 12 and 24-30 h after injection. MIP-1 alpha levels peaked
      before increases in neutrophils and lymphocytes in the DTH-reactive sponges,
      suggesting that MIP-1 alpha was responsible, at least in part, for attracting
      these leukocyte types. Immunized mice treated with neutralizing antibody to MIP-1
      alpha before sponge injection with CneF had reduced numbers of neutrophils and
      lymphocytes in the DTH-reactive sponges and showed reduced clearance of C.
      neoformans from the lungs, spleens, livers, and brains when compared with
      controls. Furthermore, injection of rmMIP-1 alpha into sponges in naive mice
      resulted in an increase in the influx of neutrophils and lymphocytes into the
      sponges compared with saline-injected sponges. Together our findings provide
      solid evidence that MIP-1 alpha is a component of the anticryptococcal DTH
      reaction. In addition, MIP-1 alpha influences neutrophil influx and attracts
      lymphocytes into the DTH reaction site. Finally, we showed that MIP-1 alpha plays
      a role in protection against C. neoformans.

PMID- 9021920
TI  - Epinephrine attenuates down-regulation of monocyte tumor necrosis factor
      receptors during human endotoxemia.
AB  - Epinephrine inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)
      production by increasing intracellular cAMP concentrations. Because agents that
      increase cAMP levels can enhance TNF receptor expression in vitro, granulocyte
      and monocyte TNF receptors were determined by FACS-analysis in 7 normal humans
      who were receiving a constant 24-h infusion of epinephrine (30 ng/kg/min), and in
      15 normal subjects after intravenous injection of LPS (2 ng/kg), while they were
      receiving a continuous infusion of epinephrine started either 3 h (EPI-3) or 24 h
      (EPI-24) before LPS injection or an infusion of normal saline (LPS; n = 5 per
      group). Infusion of epinephrine per se did not influence TNF receptor expression.
      LPS induced a transient decrease in monocyte TNF receptors and a more sustained
      decrease in granulocyte TNF receptors (both P < 0.05). EPI-3 partly prevented LPS
      induced down-modulation of monocyte TNF receptors (P < 0.05 vs. LPS only), but
      did not affect LPS-induced down-modulation of granulocyte TNF receptors. EPI-24
      had no effect on TNF receptor expression. These data suggest that epinephrine not
      only influences the bioavailability of TNF by an effect on the production of this
      proinflammatory cytokine, but also by modulating the expression of its receptors.

PMID- 9021921
TI  - Preactivation exposure of RAW 264.7 cells to taurine chloramine attenuates
      subsequent production of nitric oxide and expression of iNOS mRNA.
AB  - Recent studies demonstrate that taurine chloramine (Tau-Cl) inhibits production
      of nitric oxide (NO) and other proinflammatory mediators in cultured macrophages
      when added to the media at the time of activation. Because Tau-Cl may react with
      various media constituents and it is difficult to measure Tau-Cl in complex
      solutions, we designed experiments to more carefully control cell exposure to
      various chloramines and NaOCl. RAW 264.7 cells were exposed to 1 mM of NaOCl, Tau
      Cl, or chloramine preparations of the following amino acids: L-alanine (L-Ala
      Cl), beta-alanine (beta-Ala-Cl), serine (Ser-Cl), or glycine (Gly-Cl) in Hanks'
      balanced salt solution (HBSS) for up to 2 h (37 degrees C, 5% CO2). The HBSS
      solution was then replaced with complete media containing interferon-gamma (IFN
      gamma) and lipopolysaccharide (LPS) for an additional 24 h before measuring cell
      viability. The chemical stability of NaOCl and each chloramine was evaluated
      after various times of preactivation exposure by measuring retention of each
      solution's UV absorption spectra and ability to oxidize KI. Cytotoxicity of each
      solution was evaluated by the maintained ability of RAW 264.7 cells to reduce
      MTT. Whereas Tau-Cl, beta-Ala-Cl, and Gly-Cl were stable chloramines, only Tau-Cl
      was not cytotoxic. L-Ala-Cl, Ser-Cl, and the highly reactive oxidant NaOCl were
      unstable and toxic. In further studies RAW 264.7 cells were exposed to Tau-Cl in
      HBSS for 2 h and the solution was then replaced with complete media containing
      IFN-gamma and LPS, taxol, lipoarabinomannan, or interleukin-2. Production of NO
      was measured 24 h later and was inhibited in activated cells that were previously
      exposed to Tau-Cl. Inhibition of NO production was dependent on Tau-Cl
      concentration and was accounted for by reduced expression of inducible nitric
      oxide synthase mRNA, regardless of activator combinations. These results support
      the idea that Tau-Cl has the potential to function as an inhibitory modulator of
      inflammations.

PMID- 9021922
TI  - CD18 adhesion blockade decreases bacterial clearance and neutrophil recruitment
      after intrapulmonary E. coli, but not after S. aureus.
AB  - Leukocyte emigration in the lung occurs by both CD18-dependent and -independent
      mechanisms that are stimulus specific. We examined the effect of CD18 blockade
      (mAb 60.3) on neutrophil (PMN) emigration into, and bacterial clearance from, the
      lung. After intravenous treatment with either mAb 60.3 or saline, rabbits were
      given an intralobar inoculation with 10(9) colony-forming units of either
      Staphylococcus aureus or Escherichia coli. Four hours after inoculation, lungs
      were lavaged to assess PMN emigration. CD18 blockade reduced PMN emigration to E.
      coli by 76% but only 45% to S. aureus. Experiments to determine bacterial
      recovery from the lungs at 4, 8, and 24 h after inoculation showed that CD18
      blockade impaired the early (4 h) clearance of E. coli but not S. aureus. These
      findings suggest that PMN emigration to intrapulmonary S. aureus is largely CD18
      independent. In contrast, intrapulmonary E. coli elicits CD18-mediated PMN
      emigration. CD18 blockade results in impaired clearance of E. coli but not S.
      aureus from the lung.

PMID- 9021923
TI  - Dual effects of soluble CD14 on LPS priming of neutrophils.
AB  - To evaluate the effect of soluble CD14 (sCD14) on human neutrophil response to
      lipopolysaccharide (LPS), we developed an LPS-priming assay that measures the
      chemiluminescence response to N-formyl-methionyl-leucyl-phenylalanine
      stimulation. Priming by 1 ng/mL rough LPS occurred in the presence of either
      serum or recombinant LPS-binding protein (LBP) only. Priming was completely CD14
      dependent because preincubation of the neutrophils with an anti-CD14 monoclonal
      antibody prevented priming. We hypothesize that sCD14 enhances LPS response in
      neutrophils, but this response is not as effective as LPS response via membrane
      CD14 (mCD14). In our experiments sCD14 is present in an excess compared with
      mCD14. Priming of neutrophils occurs with low LBP, supposedly via sCD14-LPS
      complexes. With high LBP, addition of sCD14 inhibited LPS-priming of neutrophils.
      In that case, LPS may be transported to sCD14, preventing a more effective
      response via mCD14. In this study we demonstrate that the effect of sCD14 on
      neutrophil response to LPS is a delicate balance between activation and
      inhibition depending on concentration of serum or LBP.

PMID- 9021924
TI  - Endothelial P-selectin and VCAM-1 each can function as primary adhesive
      mechanisms for T cells under conditions of flow.
AB  - This study demonstrates that endothelial P-selectin and vascular cell adhesion
      molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), are
      capable of supporting extensive primary adhesion of T cells under flow. To
      address this issue, we used human umbilical vein endothelial cells (HUVECs)
      stimulated with histamine, interleukin-4 (IL-4), or interferon-gamma (IFN-gamma)
      that provide essentially a P-selectin, VCAM-1, or ICAM-1 surface, respectively,
      in a physiologically relevant cell type. Monoclonal antibody (mAb) blockade
      studies were carried out to confirm the specificity of these adhesive
      interactions and rule out a number of other potentially important adhesion
      molecules. Quantitation of adhesion showed that almost all of the interacting T
      cells rolled on histamine-stimulated HUVECs or CHO-P cell monolayers. In
      contrast, approximately 20% of the total interacting T cells with 24-h IL-4
      treated HUVECs were firmly adherent. mAb blocking experiments revealed that T
      cell adhesion to IL-4-treated HUVECs is alpha 4-VCAM-1 dependent. Furthermore,
      mAb 4B9 directed against domain 1 of VCAM-1 eliminated adhesion, suggesting that
      alpha 4 integrins may not interact with either the alternatively spliced domain 4
      of VCAM-1 or fibronectin in this process. At a wall shear stress of 2 dyn/cm2,
      the mean T cell rolling velocities were significantly lower on 24-h IL-4
      activated HUVECs (10.2 +/- 2.6 microgm/s) compared with either CHO-P cells (15.6
      +/- 3.1 microm/s) or histamine-stimulated HUVECs (16.6 +/- 6.1 microm/s). ICAM-1,
      expressed on the surface of 24-h IFN-gamma-activated HUVECs pretreated with an
      anti-VCAM-1 mAb to eliminate any VCAM-1-dependent contribution, did not support T
      cell adhesion under shear conditions. Together these data indicate that T cell
      primary adhesion can be mediate d by both endothelial P-selectin and VCAM-1 but
      not ICAM-1. alpha 4 integrins are highly versatile molecules, capable of
      initiating T cell rolling interactions and mediating firm arrest on activated
      endothelium.

PMID- 9021925
TI  - Dynamic imaging of neutrophil migration in three dimensions: mechanical
      interactions between cells and matrix.
AB  - Fluorescence confocal microscopy was used to obtain three-dimensional (3-D)
      images of human neutrophils migrating through a 3-D matrix of amniotic membrane
      with a temporal resolution of 30-60 s and a spatial resolution of approximately 2
      microm in the z-dimension. Neutrophils migrating in response to a chemoattractant
      gradient within a 3-D matrix were apparently able to generate traction by use of
      lateral pseudopods inserted into footholds in the matrix as evidenced by matrix
      distortion. Similar anchored pseudopods were seen in cells migrating across
      polycarbonate membranes with 0.8-microm pores; the presence of these pores
      increased cell polarization and migration compared with cells on membranes
      without pores. Expansion of pseudopods distal to narrow constrictions in the
      matrix and porous filters was observed and appeared to be used to pull cells
      through the openings. Neutrophils deformed parts of the elastic amnion matrix
      during migration without permanently altering the substrate. Contact guidance of
      neutrophils crawling along matrix fibrils was also observed. These observations
      show that neutrophils migrating in 3-D are able to utilize mechanical structures
      in the matrix, not present on 2-D surfaces, to generate traction for locomotion.

PMID- 9021926
TI  - CD40-CD40L interactions provide "third-party" costimulation for T cell response
      against B7-1-transfected human breast tumor cells.
AB  - In this study we provide evidence that a human breast carcinoma cell line, MDA-MB
      231 (MDA), can be made immunogenic following B7 transfection and that full T cell
      activation is obtained through cooperation of T-B lymphocytes via CD40-CD40L
      interactions. Tumor cells transfected with either B7 gene (MDAB7), neomycin
      resistant gene only (MDAneo), or untransfected (MDA) were used in an allogeneic
      mixed lymphocyte tumor culture (MLTC) to investigate their ability to stimulate T
      cell proliferation and generate cytotoxic T lymphocytes (CTL). MDAB7 induced
      moderate T cell proliferation while MDAneo or MDA did not. Substantial T cell
      proliferation and de novo generation of cytolytic T cells was obtained only in
      response to MDAB7 when B cells were present during the MLTC. CD8+-purified T + B
      cells proliferated to a greater extent than whole T cell populations + B or CD4+
      + B in response to MDAB7. Addition of alpha-B7-1 or alpha-CD40 in the MLTC
      inhibited T cell proliferation by 65 and 40%, respectively, whereas T cell
      proliferation and generation of CTL was completely abrogated when MLTC was
      performed in the presence of both antibodies. These data suggest that the
      engagement of CD40L on T cells with CD40 on B cells provides a costimulatory
      signal which, in synergism with TCR-dependent MDAB7-T cell recognition (signal 1)
      and B7/CD28 interactions (signal 2), leads to full T cell activation.

PMID- 9021927
TI  - Fas involvement in human NK cell apoptosis: lack of a requirement for CD16
      mediated events.
AB  - Propriocidal regulation of T cells refers to apoptosis induced by interleukin-2
      (IL-2) activation with subsequent antigen receptor stimulation. We previously
      reported that natural killer (NK) cells also exhibit propriocidal death. Cell
      death can be induced following occupancy of the Fc gamma RIII (CD16) receptor
      when NK cells were pretreated with IL-2, IL-12, or IL-15. Here we show other
      triggering receptors on NK cells such as CD44, anti-NK-receptor antibodies, and
      pharmacological activation can result in the cell death signal. Requirement for
      cell interactions indicated that cell contact was required; however, unlike cell
      mediated lysis, extracellular calcium was not required. Like T cells, the process
      of cell death for NK cells was receptor-induced apoptosis. Activation-induced
      apoptosis of T cells is mediated by members of the tumor necrosis factor (TNF)
      cytokine superfamily. We examined the involvement of TNF receptor family members
      or Fas in this rapid cell death. Antibody directed against Fas, TNFR60, TNFR80,
      LTBR, and LT alpha failed to inhibit receptor-induced death. Therefore, NK cells
      appear to demonstrate a rapid apoptotic episode when CD16 is cross-linked, but
      the mechanism of this apoptosis is quite different than was observed in T cells
      with CD3. The direct examination of the Fas pathway on activated NK cells
      revealed that susceptibility required longer treatment times and IL-2 activation.
      This susceptibility was paralleled by increased Fas-ligand expression. Therefore,
      NK cells can demonstrate an apoptotic response to CD16, CD44, NK receptors, and
      Fas. The enumeration of ligands capable of eliciting NK cell death and the in
      vivo relevance of this observation require further study.

PMID- 9021929
TI  - Dexamethasone-induced suppression of apoptosis in human neutrophils requires
      continuous stimulation of new protein synthesis.
AB  - We examined the mechanisms of corticosteroid inhibition of cell death by
      apoptosis in human neutrophils. Suppression of apoptosis by dexamethasone was
      abolished by co-treatment with the protein synthesis inhibitor cycloheximide. At
      doses of 1 microg/mL cycloheximide did not reduce basal survival of neutrophils
      but effectively inhibited dexamethasone-induced increases in 24-h survival (24.4
      +/- 8.7 vs. 49.6 +/- 10%, P < 0.01). Similar results were obtained with
      actinomycin D, an inhibitor of mRNA synthesis. The factor(s) responsible for
      mediating increased survival following dexamethasone treatment is not active
      extracellularly because dexamethasone-treated neutrophil-conditioned medium (CM)
      had no effect on the survival of naive neutrophils when the direct effects of
      dexamethasone were neutralized with the steroid antagonist RU-486. In contrast,
      LPS-treated neutrophil CM significantly increased neutrophil survival even after
      addition of polymyxin b. The survival effect of dexamethasone required the
      continuous presence of the agonist because addition of RU-486 caused prompt
      development of apoptosis in dexamethasone-treated cells. When naive and
      dexamethasone-treated cells were examined by mRNA differential display, a limited
      number of cDNA bands were consistently and reproducibly detected that were
      increased in intensity, indicating up-regulation by dexamethasone. Thus,
      corticosteroid regulation of neutrophil apoptosis is a specific effect that
      depends on continuous stimulation of synthesis of a (protein) survival factor.

PMID- 9021928
TI  - Regulation of cytokine expression in macrophages and the Langerhans cell-like
      line XS52 by calcitonin gene-related peptide.
AB  - Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by
      Langerhans cells (LC) and macrophages, and LC are anatomically associated with
      CGRP-containing epidermal nerves. To determine whether CGRP may produce some of
      its functional effects through regulation of cytokine expression, we utilized
      enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine
      production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line
      XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to
      examine levels of mRNA for IL-10, IL-1 beta, and the 40-kDa subunit (p40) of IL
      12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) -induced release of IL-10 protein and the induced
      expression of IL-10 mRNA in these cells. However, it suppressed the induction of
      release of IL-1 beta protein and the induction of mRNA for IL-12 p40 and IL-1
      beta by LPS and GM-CSF. Regulation of cytokine expression in peritoneal
      macrophages was also examined. By ELISA, the LPS-induced expression of IL-10 was
      augmented by CGRP, whereas the induction of IL-1 beta was suppressed. Northern
      analysis demonstrated augmentation of LPS-induced IL-10 mRNA levels and
      inhibition of LPS-induced IL-1 beta mRNA by CGRP. CGRP inhibited the LPS-induced
      induction of IL-12 mRNA as assessed by RT-PCR. Up-regulation of B7-2 expression
      by LPS and GM-CSF was suppressed by CGRP in both XS52 cells and macrophages, as
      previously reported. This suppression, however, could be abrogated by co-culture
      with neutralizing antibodies to IL-10. Furthermore, the presence of neutralizing
      antibodies to IL-10 during exposure of epidermal cells (EC) to CGRP prevented the
      CGRP-mediated suppression of EC presentation of tumor-associated antigens (from
      the S1509a spindle cell carcinoma) for elicitation of delayed-type
      hypersensitivity in S1509a-immune mice. These data suggest that suppression of
      antigen-presenting function by CGRP is mediated, at least in part, by changes in
      cytokine expression that favor less robust antigen presentation for cell-mediated
      immunity.

PMID- 9021930
TI  - Taurine and inflammation--a new approach to an old problem?

PMID- 9021931
TI  - Treatment of hepatocellular carcinoma.

PMID- 9021932
TI  - Nitric oxide donors stimulate bile flow and glutathione disulfide excretion
      independent of guanosine 3',5'-cyclic [corrected] monophosphate in the isolated
      perfused rat liver.
AB  - Nitric oxide (NO) modulates several metabolic functions in hepatocytes, but the
      role of NO in bile secretion has not been clearly defined. In the present study,
      we examined the effects of NO on bile flow and biliary HC03- and glutathione
      excretion in the isolated perfused rat liver and assessed the role of guanosine
      3',5'-cyclic monophosphate (cGMP) in mediating these effects. The NO donors
      sodium nitroprusside (SNP) and S-nitroso-acetyl-penicillamine stimulated bile
      flow and increased both HCO3- and glutathione excretion. Increases in bile flow
      were linearly related to increases in biliary glutathione concentration and
      output (P < .0001), which were almost entirely caused by glutathione disulfide,
      whereas the excretion of reduced glutathione remained unchanged. NO donors
      increased cGMP concentrations in bile and perfusate, and the membrane-permeant
      cGMP analogue dibutyryl cGMP was also found to stimulate bile flow and HCO3-
      excretion. However, in contrast to the NO donors, dibutyryl cGMP did not increase
      glutathione excretion. Furthermore, the NO donors failed to stimulate bile flow
      in mutant TR- rats in which the canalicular transport of glutathione and
      glutathione conjugates is deficient, although dibutyryl cGMP increased bile flow
      and HCO3- excretion in the mutant rats as in normals. These findings indicate
      that exogenous sources of NO increase bile acid-independent bile flow by
      stimulating glutathione disulfide excretion, effects that are independent of
      cGMP.

PMID- 9021933
TI  - Cystic fibrosis transmembrane conductance regulator mediates the cyclic adenosine
      monophosphate-induced fluid secretion but not the inhibition of resorption in
      mouse gallbladder epithelium.
AB  - We have studied the physiological role of the cystic fibrosis (CF) gene product
      (cystic fibrosis transmembrane conductance regulator [CFTR]) in gallbladder
      epithelium using a knockout mouse model for CF. We found that normal mouse
      gallbladder epithelium expresses functional CFTR as shown by reverse
      transcription polymerase chain reaction (RT-PCR) analysis and Ussing chamber
      experiments. Gallbladders from Cftr -/- mice were structurally intact as shown by
      microscopic and physiological parameters but lacked the cyclic adenosine
      monophosphate (cAMP)-induced chloride current observed in normal gallbladders. In
      fluid transport measurements, normal and Cftr -/- gallbladders were equally
      active in basal resorption. The addition of forskolin, which activates CFTR anion
      channel activity through the cAMP system, resulted in net fluid secretion in
      normal gallbladders. In contrast, Cftr -/- gallbladders were unable to secrete
      fluid while a complete inhibition of resorption by forskolin was observed. We
      conclude that, in normal mouse gallbladder epithelium, cAMP-induced fluid
      secretion involves simultaneous inhibition of apical sodium chloride resorption
      and activation of CFTR. Our data support the hypothesis that gallbladder disease
      in CF is at least in part caused by a deficient secretory response to the
      endogenous cAMP-linked hormones VIP and secretin.

PMID- 9021934
TI  - Benzoic acid metabolism reflects hepatic mitochondrial function in rats with long
      term extrahepatic cholestasis.
AB  - Benzoic acid metabolism, which is primarily a function of liver mitochondria,
      depending on the concentration of adenosine triphosphate (ATP), coenzyme A (CoA),
      and glycine in the mitochondrial matrix, was investigated in both rats with long
      term cholestasis caused by bile duct ligation (BDL) and sham-operated control
      rats. In isolated liver mitochondria, hippurate production from benzoate in the
      presence of saturating glycine concentrations was reduced in BDL rats by 36% with
      L-glutamate as a source for ATP, by 21% in the presence of succinate, and by 31%
      in the presence of ATP plus oligomycine. This reduction in benzoate metabolism is
      in the same range as the previously observed reduction in the activity of the
      electron transport chain in liver mitochondria from BDL rats. The mitochondrial
      CoA pool, which can be rate-limiting for benzoic acid metabolism, was not
      different between BDL and control rats. The activity of benzoyl-CoA synthase, the
      enzyme catalyzing the rate-limiting step in benzoate metabolism, was reduced by
      25%, and the activity of benzoyl-CoA:glycine N-transferase was reduced by 66% in
      BDL rats. The activity of benzoyl-CoA synthase was significantly inhibited by
      lithocholate, suggesting that hepatic accumulation of hydrophobic bile acids
      could contribute to the observed reduction of benzoate metabolism in BDL rats.
      Benzoate metabolism was also studied in vivo by monitoring the urinary hippurate
      excretion after intraperitoneal administration of benzoate (100 micromol/100 g of
      body weight). The time course of hippurate excretion was not different between
      BDL and control rats. Hippurate excretion over 24 hours after benzoate
      administration averaged 89.7 +/- 4.0% of the administered dose in BDL and 74.4 +/
      6.9% (mean +/- SEM, difference not significant) in control rats. This finding
      could be explained by an increase in mitochondrial protein in BDL rats, averaging
      2.34 +/- 0.29 g per liver in BDL and 1.35 +/- 0.07 g per liver in control rats
      (mean +/- SEM, p < .05). Thus, the studies show that benzoate metabolism reflects
      mitochondrial function in BDL rats both in vivo and in vitro, and that
      mitochondrial proliferation compensates for the observed decrease in benzoic acid
      metabolism in isolated mitochondria in vitro.

PMID- 9021935
TI  - Expression of the rat liver Na+/taurocholate cotransporter is regulated in vivo
      by retention of biliary constituents but not their depletion.
AB  - Expression and function of the hepatic Na+/taurocholate cotransporter (ntcp) are
      down-regulated in several models of experimental cholestasis. To test whether
      retention and/or depletion of biliary constituents are involved in ntcp
      regulation, ntcp expression was quantified in several animal models with altered
      levels of these constituents. In choledochocaval fistula rats (CCF) (retention
      model), ntcp mRNA expression specifically declined after 1 and 3 days by 76 +/-
      4% (P < .005) and 31 +/- 9% (P < .05), respectively, returning to control levels
      by 7 days. However, protein expression as assessed by Western blotting remained
      unchanged for up to 7 days of CCF. In rats with bile fistulas (depletion model)
      for 0.5, 1, 2, 4, and 7 days, both ntcp protein and mRNA expression remained
      unaltered. Infusion of either taurocholate or taurochenodeoxycholate for 12 hours
      also did not effect ntcp mRNA expression in intact animals, probably because of
      its inability to increase serum and intrahepatic bile acid levels. In rats with
      selective bile duct ligation (SBDL), ntcp mRNA levels were down-regulated by 40
      +/- 10% (P < .05) only after 12 and 24 hours in ligated lobes, and mRNA levels
      returned to control values in these lobes after 2 and 4 days. ntcp mRNA
      expression remained unchanged in the nonobstructed lobes at any time. When data
      from CCF and SBDL rats were combined, serum bile acids correlated linearly with
      ntcp mRNA (r = .62, P < .0005) over a 0 to 110-micromol/L range. Our results
      indicate that ntcp is constitutively expressed and remains uneffected by either
      depletion or increased flux of biliary constituents. However, retention of
      biliary constituents results in rapid down-regulation of ntcp mRNA, consistent
      with the concept that hepatocytes may be protected from bile acid toxicity during
      cholestasis by this mechanism.

PMID- 9021936
TI  - Improvement in cholestasis-associated fatigue with a serotonin receptor agonist
      using a novel rat model of fatigue assessment.
AB  - Fatigue is a common complaint in patients with liver disease; however, the
      etiology of fatigue is poorly understood and no therapeutic options are available
      to treat it. Altered central neurotransmission, especially serotonergic, appears
      to play a role in the genesis of fatigue. In this study, we describe a rat model
      of fatigue assessment using a swim tank, and we used this model to document the
      degree of fatigue in rat models of cholestasis caused by bile duct resection
      (BDR) and of hepatitis caused by carbon tetrachloride (CCl4) administration.
      Fatigue was quantitated as the time spent floating and struggling over a 15
      minute period after placement in the swim tank, and an overall activity score was
      calculated. Using this technique, BDR rats exhibited significantly enhanced
      floating times and an overall reduction in activity score compared with
      noncholestatic controls (P < or = .01). On the other hand, CCl4-treated rats
      showed a marked variability in floating and struggling times and activity scores
      such that, overall, CCl4-treated rats were not significantly different from
      normal controls. Therefore, we used BDR and noncholestatic control rats to
      examine the effects of a serotonin (5HT1A) receptor agonist (LY293284) on
      cholestasis-associated fatigue. BDR rats treated with LY293284 (0.3 mg/kg
      subcutaneously 24, 5, and 1 hour before placement in the swim tank) showed marked
      reductions in floating times and an increase in overall activity scores compared
      with BDR controls (P < or = .001). LY293284 was without effect in noncholestatic
      animals. These results suggest that fatigue can be quantitated in rat models of
      liver disease and that 5HT1A receptor agonists may provide a useful therapeutic
      tool in the treatment of cholestatic liver disease-associated fatigue.

PMID- 9021937
TI  - Regional cerebral edema and chloride space in galactosamine-induced liver failure
      in rats.
AB  - The pathogenesis of cerebral edema, which is a major complication of fulminant
      hepatic failure, is poorly understood. In previous studies, increased regional
      brain water content was observed in rats at an early stage of acute liver failure
      caused by galactosamine. At a later stage when the animals had developed deep
      coma, brain water content was reduced, possibly as a result of generalized
      dehydration. In the present investigation, we have determined brain water content
      at a late stage of liver failure, 48 hours after galactosamine, in animals that
      had been maintained in fluid balance by continuous intraperitoneal infusion of
      glucose solution. In these animals, brain water content, determined from the
      ratio of wet to dry weight, showed a greater increase than that observed
      previously at the early stage (hindbrain region [cerebellum, pons, and brain
      stem] increased by 4.2%; forebrain region increased by 1.4% compared with
      controls). Regional analysis of brain water, using a tissue-specific gravity
      method, showed a significant increase in cerebellar gray matter water content.
      Analysis of chloride space showed the extra fluid to be mainly extracellular in
      the hindbrain region, but not in the forebrain region. Ultrastructural
      examination of capillaries in gray matter from cerebellum and cerebrum showed no
      evidence of gross disruption of the tight junctions. Swelling of the astroglial
      foot processes was observed in the cerebellar gray matter. These results suggest
      that both vasogenic and cytotoxic mechanisms of edema formation occur in the
      brain during liver failure.

PMID- 9021938
TI  - Neural networks as predictors of outcomes in alcoholic patients with severe liver
      disease.
AB  - We developed and evaluated neural networks as predictors of outcomes in alcoholic
      patients with severe liver disease using commonly available clinical and
      laboratory values. Hospital charts of 144 patients were reviewed. Nine variables
      (five laboratory, four clinical) were recorded along with in-hospital death or
      survival. Data were organized into separate development and validation sets.
      Neural network predictions of survival were compared with those of the Maddrey
      discriminant function and logistic regression models developed on the same data.
      Model performance was evaluated by comparing areas under receiver-operating
      characteristic (ROC) curves and the distributions of model scores. Survivors had
      significantly different laboratory and clinical characteristics, the most
      important being a higher prothrombin time, lower bilirubin, and lower incidence
      of encephalopathy. Neural network performance was significantly better than that
      of the Maddrey score (ROC areas, 81.5% vs. 73.8%; P = .04). The ROC area for
      neural networks was similar to that of logistic regression (ROC area 78.2%; P =
      .3), but the neural networks were more successful in classifying patients into
      low- and high-risk groups (P < .001). A neural network score with laboratory data
      from hospital-day 7 improved prognostic accuracy further to 84.3%. After
      adjusting for baseline risk, the neural network change in illness severity was
      still a significant predictor of mortality (P = .001). Neural networks using
      clinical and laboratory data showed a high prognostic accuracy for predicting
      mortality in alcoholic patients with severe liver disease.

PMID- 9021939
TI  - Risk factors for hemorrhage from gastric fundal varices.
AB  - The incidence and the risk factors of hemorrhage from gastric fundal varices (FV)
      have not been fully evaluated. We therefore conducted a retrospective and
      prospective study to define the incidence and risk factors for such episodes. We
      investigated 132 patients with cirrhosis and gastric FV. Of these 132 patients,
      15 patients had hemorrhagic FV at the time of enrollment. The clinical
      characteristics were compared between these patients and those without a first
      hemorrhage from FV. In the patients who had never previously bled, the incidence
      and risk factors were prospectively investigated. The size of FV was greater and
      red-spot on the FV were more prevalent in patients with hemorrhagic FV. Child's
      status was also more severe in these patients. In the 117 patients who had never
      bled, 34 hemorrhages from FV occurred during the follow-up period. The cumulative
      risk for such hemorrhage at 1, 3, and 5 years was 16%, 36%, and 44%,
      respectively. A multiple regression analysis (Cox's model) revealed the size of
      varices, red-spot on the FV, and Child's status to be statistically significant,
      as well as independent predictors for hemorrhage from FV. The endoscopic criteria
      (size of the largest varix and presence of red-spot), as well as the hepatic
      functional reserve, provide the most essential information for predicting a
      hemorrhage from FV. An estimation of the probability for hemorrhage from FV based
      on Cox's model may therefore be beneficial in the clinical management of patients
      with high-risk FV.

PMID- 9021940
TI  - Lack of renal effects of fish oil administration in patients with advanced
      cirrhosis and impaired glomerular filtration.
AB  - The treatment of renal failure in cirrhotic patients with ascites remains
      unsatisfactory. Recent studies have shown that the dietary supplementation with
      fish oil improves the renal function of normal subjects, as well as that of
      patients with renal failure of different etiologies. We have investigated the
      renal effects of a daily supplementation for 1 month of 12 g fish oil (27% C20:5
      n-3 eicosapentanoic acid [EPA], and 23% C22:6 n-3 docosahexanoic acid [DHA]) in a
      prospective study of cirrhotic patients with ascites, nine with normal renal
      function (group 1) and eight with renal failure (glomerular filtration rate [GFR]
      < 60 mL/min, group 2). Compliance with the dietary regimen was confirmed by fatty
      acid chromatography that showed increased plasma concentration of EPA (from 1.5
      +/- 0.7% to 3.7 +/- 0.8%, P = .024, in group 1; and from 0.53 +/- 0.3% to 2.9 +/-
      0.8%, P = .03, in group 2) and of DHA (from 2.1 +/- 0.4% to 3.4 +/- 0.3%, P =
      .008, in group 1; and from 1.45 +/- 0.5% to 3.8 +/- 0.4%, P = .05, in group 2).
      At the end of the study, in patients from group 1, the glomerular filtration rate
      increased by 19% (from 94 +/- 8 to 113 +/- 13 mL/min, P = .039), and the urine
      flow increased by 39% (from 0.85 +/- 0.14 to 1.12 +/- 0.2 mL/min, P = .039),
      while no changes occurred in the renal function of patients from group 2. No
      changes were observed in the urinary excretion of prostaglandin (PG) E2 or of 6
      keto prostaglandin-1-alpha (6-K-PGF1-alpha) nor in plasma renin activity (PRA) or
      the plasma concentration of aldosterone (PA) or antidiuretic hormone (ADH) in
      both groups. As far as undesirable effects of fish oils were considered, the mean
      arterial pressure (MAP) decreased in both groups (group 1: from 88.6 +/- 2 to
      85.3 +/- 2 mm Hg, P = .015; group 2: from 88.2 +/- 3 to 82.8 +/- 3 mm Hg, P =
      .05), and bleeding time displayed a significant increase when patients were
      considered collectively (from 744 +/- 89 to 872 +/- 106 seconds, P = .0068). In
      conclusion, the administration of fish oil for 1 month was unable to improve
      renal function in cirrhotic patients with ascites and renal failure. The
      occurrence of undesirable effects, such as the reduction of arterial pressure and
      the prolongation of bleeding time, argues against the use of fish oils in these
      patients.

PMID- 9021941
TI  - Associations between alleles of the major histocompatibility complex and type 1
      autoimmune hepatitis.
AB  - Susceptibility for type 1 autoimmune hepatitis has been associated with the major
      histocompatibility alleles DRB1*0301, DRB3*0101, DRB1*0401, and DRB4*0103,
      whereas the DRB1*1501 allele may protect from the disease. Our aim was to
      determine if these alleles or others influence clinical manifestations and
      prognosis. Eighty-six white patients were evaluated prospectively for immune
      features and outcomes. Class I alleles were determined by
      microlymphocytotoxicity, and class II alleles were assessed by polymerase chain
      reaction with sequence-specific oligonucleotide probes or sequence-specific
      primers. One hundred two white, normal subjects were typed in the same fashion.
      Patients with concurrent immunologic diseases were more commonly positive for
      DRB4*0103 than patients without these features (68% vs. 38%, P = .01). DRB1*0301
      (86% vs. 45%, P = .008) and the DRB1*0301-DRB3*0101 haplotype (79% vs. 42%, P =
      .02) occurred more commonly in patients who deteriorated during corticosteroid
      therapy. In contrast, DRB1*0401 and the DRB1*0401-DRB4*0103 haplotype were
      associated with a lower frequency of death from liver failure or the need for
      transplantation than patients with other alleles (0% vs. 37%, P = .03). Patients
      with DRB1*0301 differed from those with DRB1*0401 in that they were younger and
      failed treatment more commonly (27% vs. 5%, P = .04). We conclude that alleles
      associated with susceptibility to type 1 autoimmune hepatitis also influence its
      clinical features and prognosis. DRB4*0103 is associated with concurrent immune
      diseases, DRB1*0301 with a poor treatment response, and DRB1*0401 with a lower
      frequency of hepatic death or transplantation.

PMID- 9021942
TI  - Gene expression of glucokinase regulatory protein in regenerating rat liver.
AB  - The activity and messenger RNA (mRNA) levels of glucokinase, and the
      concentration and mRNA levels of its regulatory protein, were analyzed during
      liver regeneration. The activity of glucokinase and the concentration of its
      regulatory protein decreased to 30% and 50%, respectively, after liver resection,
      remaining low after 1 week. No significant variations in the level of these
      proteins were found in sham-operated animals. The regulatory protein/glucokinase
      molar ratio increased during the replicative phase, to a maximum at 48 hours. The
      mRNA levels of glucokinase and of its regulatory protein decreased rapidly after
      partial hepatectomy to minimum values at 6 hours (15%) and at 12 hours (4%),
      respectively, returning to normal values at 24 hours and 168 hours, respectively.
      Sham-operated animals showed a similar decrease in mRNA levels during the
      prereplicative phase of liver regeneration, suggesting that the initial effects
      observed in the gene expression of these proteins were due to surgical stress.
      During the replicative phase, a specific inhibition of the regulatory protein's
      gene expression was observed in the regenerating liver. A decrease in the content
      of regulatory protein and the glucokinase activity, and an increase in the molar
      ratio of these two proteins correlate with the observed decrease in glycolytic
      flux, providing further evidence that the phosphorylation of glucose is a control
      point in the glycolytic/gluconeogenic flux during liver regeneration.

PMID- 9021943
TI  - Isolation of oval cells from Long-Evans Cinnamon rats and their transformation
      into hepatocytes in vivo in the rat liver.
AB  - Oval cells function as compensatory cells in severe liver injury and are thought
      to be equivalent to liver stem/progenitor cells. We isolated oval cells from the
      liver of Long-Evans Cinnamon (LEC) rats by isopyknic centrifugation in a Percoll
      gradient. The cells were gamma-glutamyl transpeptidase (GGTP)-positive, alpha
      fetoprotein-positive, and cytokeratin (CK) 18- and CK 19-positive, but albumin
      negative in the cells. When oval cells were transplanted to the liver, they were
      transformed into hepatocytes. To evaluate albumin biosynthesis, we transplanted
      oval cells into the liver of Nagase analbuminemic and LEC double mutant rats. The
      albumin level in the serum of transplanted rats was increased and maintained for
      up to 10 weeks. These results indicated that the oval cells isolated from LEC
      rats can differentiate into hepatocytes in vivo.

PMID- 9021944
TI  - Chronic alcohol intoxication induces hepatic injury through enhanced macrophage
      inflammatory protein-2 production and intercellular adhesion molecule-1
      expression in the liver.
AB  - This study tested the hypothesis that prolonged consumption of alcohol directly
      or indirectly, through endotoxin influx in the circulation, stimulates the
      Kupffer cells to produce macrophage inflammatory protein-2 (MIP2) and up
      regulates the expression of adhesion molecules, i.e., CD18 on PMNs and its
      counter-receptor, intercellular adhesion molecule-1 (ICAM-1), on hepatic cells.
      As a result, enhanced sequestration and cell-cell interaction among these cell
      types may occur in the liver, which in turn could result in altered hepatic
      function and hepatotoxicity. This hypothesis was tested in alcohol-fed, specific
      pathogen-free, male Sprague-Dawley rats. After 16 weeks of feeding, endotoxin
      (0.2 +/- 0.043 EU/mL) and MIP2 (625 +/- 100 pg/mL) were detected in the sera of
      alcoholic rats but not in the pair-fed rats. Concomitantly, serum aspartate
      transaminase (AST) activity was significantly increased. Small lipid deposition
      and inflammatory-like changes in the liver were also observed. Isolated Kupffer
      cells from alcohol-fed rats released large amount of MIP2 (> 600 pg/10(6) Kupffer
      cells/24 hr) in vitro compared with Kupffer cells from pair-fed rats (< 150
      pg/10(6) Kupffer cells/24 hr). At the same time, the expression of CD18 and ICAM
      1 on polymorphonuclear neutrophils (PMNs) and hepatic cells was increased more
      than twofold. Monoclonal antibody 1F12, an anti-CD18 antibody, attenuated hepatic
      injury in vivo, and in PMN-hepatocyte coculture in vitro in the alcohol-fed
      group. Another factor that could contribute to hepatic injury was MIP2, which was
      cytotoxic to alcoholic hepatocytes in vitro. This was reversed by cycloheximide,
      thus suggesting the indirect hepatotoxic effect of MIP2. In addition, isolated
      PMNs and Kupffer cells from alcohol-fed rats released large amounts of
      superoxide, which may also play a role in hepatic injury. These results
      demonstrate that MIP2 and adhesion molecules may contribute, at least in part, in
      the initiation of hepatic injury during alcohol intoxication.

PMID- 9021945
TI  - Prenatal alcohol exposure affects galactosyltransferase activity and
      glycoconjugates in the Golgi apparatus of fetal rat hepatocytes.
AB  - Prenatal exposure to alcohol affects the morphological, structural, and
      functional features of the Golgi apparatus (GA), thus altering the glycosylation
      process in fetal hepatocytes. To elucidate the cellular mechanisms underlying
      these alterations, we have studied the effect of alcohol exposure in utero on the
      activity of liver galactosyltransferase, an enzyme involved in the glycosylation
      process, and on the hepatic glycoprotein sugar composition. For this, livers from
      21-day-old fetuses obtained from control and ethanol-fed rats were used.
      Galactosyltransferase (GT) activity was determined in isolated GA cis and trans
      fractions. Colloidal gold-labeled lectin cytochemistry was used to analyze sugar
      residues in hepatocytes at the subcellular level. Finally, the integrity of the
      GA after alcohol treatment was assessed by electron microscopy and by evaluating
      the distribution of the Golgi beta-COP, a protein involved in vesicular
      trafficking. Prenatal alcohol exposure induces a significant increase in both
      liver weight and total protein content in the trans Golgi. Moreover, this
      treatment decreases the activity of galactosyltransferase, increases alpha-L-Fuc
      residues, and reduces the number of alpha-Man, GlcNAc(beta1,4,GlcNAc)1,2, GalNAc
      alpha1,3GalNAc, alpha-GalNAc, and a-Gal residues. Alcohol exposure also causes
      the Golgi cisternae to disappear in about 30% of the hepatocytes, and reduces 75%
      the number of anti-Golgi beta-COP protein binding sites. Our results suggest that
      the decrease in galactosyltransferase activity, the alterations in the
      oligosaccharide chain composition, and the reduction in the amount of Golgi beta
      COP protein could be involved in the alterations in the glycosylation process, as
      well as in the accumulation of hepatic proteins observed after prenatal alcohol
      exposure. These alterations could contribute, therefore, to the alcohol-induced
      injury in the developing liver.

PMID- 9021946
TI  - Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in
      relation to liver pathology.
AB  - Liver lipid peroxidation, nonheme iron, antioxidants, and protein oxidation were
      investigated in experimental alcohol-induced liver disease in the rat. Wistar
      male rats were intragastrically and continuously infused for 4 weeks with a high
      fat diet plus an ethanol or an isocaloric amount of dextrose, maintaining a high
      blood alcohol level (200-300 mg%). This model induced fatty liver, spotty
      necrosis, and focal inflammation. This pathology was associated with an enhanced
      lipid peroxidation and a decrease in the major antioxidant factors. Hepatic alpha
      tocopherol and glutathione concentrations were significantly decreased in ethanol
      fed rats. Glutathione peroxidase (GPx) was also decreased, whereas glutathione S
      transferase (GST) was unaffected. The nonheme iron level was significantly
      decreased. Protein oxidation was assessed through three parameters: protein
      thiols, protein carbonyl groups, and the activity of glutamine synthetase (GS), a
      centrilobular enzyme particularly susceptible to free-radical-mediated damage.
      Ethanol-fed rats had decreased protein thiol concentrations and reduced GS
      activity, together with increased protein carbonyls. A significant correlation
      between GS activity and the pathological score was observed. This study confirms
      the ethanol-related increase in lipid peroxidation and shows that ethanol impairs
      the hepatic antioxidant potential. Furthermore, evidence of oxidative protein
      damage is given, including decreased activity of a key enzyme of ammonia
      metabolism. These protein disturbances may contribute to the pathogenesis of the
      observed liver damage.

PMID- 9021947
TI  - Kupffer cells generate superoxide anions and modulate reperfusion injury in rat
      livers after cold preservation.
AB  - This study was designed to determine the source of reactive oxygen species (ROS)
      and whether Kupffer cells modulate the injury of perfused rat liver after cold
      preservation. The livers of male Lewis rats pretreated with schizophyllan glucan
      (SPG) (10 mg/kg, SPG group) or gadolinium chloride (5 mg/kg; Gd group) and
      untreated rats (control group) were preserved in University of Wisconsin solution
      for 0, 12, and 24 hours at 4 degrees C and then perfused for 60 minutes with
      oxygenated Krebs-Henseleit bicarbonate buffer. Real-time chemiluminescence (CL)
      of the liver during perfusion was measured using a sensitive photomultiplier, and
      reperfusion injury was assessed by measuring lipid peroxidation and lactate
      dehydrogenase release. CL intensity reached a peak within 5 minutes of
      reperfusion, and superoxide dismutase completely inhibited this CL in all groups.
      In the control group, the total CL intensity was high after 24 hours of
      preservation. It significantly (P < .05 vs. control group) increased in the SPG
      group, while it decreased in the Gd group after 12 and 24 hours of preservation.
      The total CL intensity decreased by 70% (when diphenyliodonium chloride (100
      micromol/L; an NADPH oxidase inhibitor) was added to the perfusate before
      preservation of untreated rats. Lipid peroxidation and lactate dehydrogenase
      release significantly (P < .05) deteriorated in the SPG group, while they
      ameliorated in the Gd group after 24 hours of preservation. These results
      demonstrate that Kupffer cells primarily generate superoxide anions and modulate
      the organ injury in the initial phase of reperfusion after cold preservation.

PMID- 9021948
TI  - Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates
      collagen synthesis in human hepatic stellate cells: role of nitric oxide.
AB  - Experimental evidence indicates that the lipid peroxidation of biological
      membranes is often associated with the development of liver fibrosis. We have
      studied the effect of neutrophil-derived reactive oxygen species (ROS) on
      collagen synthesis by human hepatic stellate cells (HSC), the major source of
      collagen in the liver, in a coculture system. Lipid peroxidation in the
      cocultures was evaluated in terms of either malondialdehyde (MDA) production or
      the formation of MDA/4-hydroxynonenal protein adducts. The expression of cellular
      messenger RNAs (mRNAs) was evaluated by either Northern blotting or RNAse
      protection assay. Nitric oxide (NO) synthase activity in cells was measured by
      [3H]citrulline formation from [3H]arginine. In vitro exposure of HSC to ROS
      resulted in the early induction of lipid peroxidation and was associated with a
      marked increase (threefold) of procollagen I mRNA expression and synthesis. The
      addition of antioxidants, such as vitamin E or superoxide dismutase (SOD),
      impaired this stimulation. The inhibition of neutrophil NO formation by N(G)
      monomethyl-L-arginine made the ROS-induced stimulation of procollagen I more
      evident. The addition of xanthine/xanthine oxidase X/XO, a superoxide anion
      donor, to HSC cultures strongly increased procollagen I synthesis. This
      stimulation was hampered by the addition of both SOD and sodium nitroprusside (an
      NO donor). The contribution of HSC to the production of NO in our coculture
      system was negligible, because inducible NO synthase (iNOS) mRNA was almost
      undetectable in these cells, and also because the amount of NO produced by HSC
      stimulated with tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide
      (LPS) was 500 times less than that synthesized by neutrophils. In conclusion,
      these results indicate that neutrophil-derived ROS may contribute to the
      development of hepatic fibrosis associated with alcoholic hepatitis. NO produced
      by neutrophils may exert a "protective" antioxidant effect by operating as a
      scavenger of superoxide anion.

PMID- 9021949
TI  - Oxidative stress-mediated apoptosis of hepatocytes exposed to acute ethanol
      intoxication.
AB  - The present study was designed to investigate whether acute ethanol intoxication
      increases the production of active oxidants, and subsequently promotes apoptosis
      of hepatocytes. Hepatocytes were isolated from male Wistar rats, and cultured in
      the presence or absence of ethanol. The fluorescence in situ nick end labeling
      method and an enzyme-linked immunosorbent assay (ELISA) system to quantify
      fragmented DNA were used to estimate apoptotic change in hepatocytes. Nuclear
      morphological alterations and membrane barrier dysfunction of hepatocytes were
      assessed by staining with Hoechst 33342 and propidium iodide (PI). Intracellular
      glutathione level was determined as the fluorescence of monochlorobimane (MCLB),
      which forms conjugate with glutathione to become fluorescent. Ethanol (100
      mmol/L) increased the amount of fragmented DNA and the number of apoptotic
      hepatocytes in vivo as well as in vitro. These ethanol-induced alterations in
      hepatocytes were attenuated by simultaneous incubation with either 4
      methylpyrazole, an inhibitor of alcohol dehydrogenase, or dimethylthiourea, an
      intracellular oxidant scavenger. Diethyl maleic acid (DMA), a glutathione
      depletor, enhanced the induction of apoptotic change, and decreased membrane
      barrier function in ethanol-treated hepatocytes, whereas ethanol per se did not
      increase the number of PI-positive hepatocytes. Furthermore, combination of
      ethanol and DMA but not ethanol alone decreased the hepatocyte MCLB fluorescence.
      Taken together, the present study suggests that active oxidants produced during
      ethanol metabolism mediate fragmentation of DNA in hepatocytes, and that
      intracellular antioxidants such as glutathione play a critical role in the
      cytoprotective mechanisms of hepatocyte against lethal cell death, ie, apoptosis,
      induced by ethanol.

PMID- 9021950
TI  - Altered hepatocellular Ca2+ regulation during hemorrhagic shock and
      resuscitation.
AB  - The present study evaluated the effect of the benzothiazepine Ca2+ channel
      blocker diltiazem (DZ) on altered hepatocellular Ca2+ regulation and oxidant
      injury during hemorrhagic shock/resuscitation. In anesthetized, male Sprague
      Dawley rats, hemorrhagic shock was induced by rapid blood withdrawal and
      maintaining the mean arterial blood pressure at 40 mm Hg over 60 minutes. Rats
      were then resuscitated with 60% of shed blood and threefold the shed blood volume
      of Ringer's lactate. At the end of ischemia, and 60 or 300 minutes after
      resuscitation, hepatocytes were isolated by liver collagenase perfusion.
      Hepatocellular Ca2+ exchange (Ca2+ex), rate of cellular Ca2+ influx (Ca2+in), and
      Ca2+ membrane flux (Ca2+flux) were determined using 45Ca incubation techniques.
      Hepatocyte oxidant injury was evaluated by fluorometrically measuring
      thiobarbituric acid reactive substances and oxidized/reduced glutathione. Both
      hemorrhage and hemorrhage/resuscitation increased hepatocellular Ca2+in, Ca2+ex,
      and Ca2+flux. In contrast to control and sham-operated rats, in vitro stimulation
      by the Ca2+ agonist epinephrine (100 nmol/L) of hepatocytes from either
      hemorrhaged or resuscitated rats did not further increase Ca2+in. Administration
      of DZ (.8 mg/kg) with resuscitation significantly decreased cellular Ca2+ex and
      Ca2+flux, but did not restore impaired epinephrine-induced Ca2+in. DZ prevented
      hepatocyte lipid peroxidation and glutathione oxidation. These findings suggest
      hepatocellular Ca2+ overload and impaired Ca2+ signaling during
      hemorrhage/resuscitation. Increased Ca2+ uptake could be because of a receptor
      gated Ca2+ influx and/or oxygen-free radical induced membrane Ca2+ leaks.

PMID- 9021951
TI  - Membrane potential of hepatic mitochondria after acute cocaine administration in
      rats--the role of mitochondrial reduced glutathione.
AB  - Cocaine hepatotoxicity may be mediated by oxidative damage, possibly involving
      mitochondrial injury. The effect of an acute dose of cocaine in rats on the
      mitochondrial level of reduced glutathione, nicotinamide adenine dinucleotide
      (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), important
      determinants in cellular defense against oxidative stress, was investigated.
      Under these conditions, the extent of lipid peroxidation was assessed as
      thiobarbituric acid reactive substances formation and the energy transducing
      capability of the inner mitochondrial membrane was evaluated by membrane
      potential measurements. Female Wistar albino rats were given an acute 50 mg/kg
      intraperitoneal dose of cocaine and, 6 hours later, hepatic and mitochondrial
      biochemical analyses were made. Rats administered intraperitoneally, 7.5 hours
      before the sacrifice, a specific inhibitor of glutathione synthesis, L-buthionine
      (S,R)-sulphoximine, either alone or in combination with cocaine, underwent in
      parallel the same determinations. Cocaine intoxication did not impair
      mitochondrial functions, although a significant increase of lipid peroxidation
      occurred. By contrast the combination of L-buthionine-(S,R)-sulphoximine with
      cocaine induced a severe derangement of mitochondrial functional efficiency, a
      large depletion of reduced glutathione, and a further enhancement of lipid
      peroxidation. The mitochondrial functional anomalies were largely restored by the
      use of cyclosporin A, ethyleneglycotetraacetic acid (EGTA) and glutathione
      methylmonoester. A nonspecific calcium dependent inner membrane permeabilty
      transition (pore opening) accounted for the partial loss of mitochondrial coupled
      functions at a period of cocaine intoxication when no cell damage occurred. The
      level of mitochondrial glutathione played a critical role in protecting inner
      membrane functional integrity against cocaine-induced oxidative stress.

PMID- 9021952
TI  - Regulation of rat liver S-adenosylmethionine synthetase during septic shock: role
      of nitric oxide.
AB  - We investigated the modulation of rat liver S-adenosylmethionine (SAM) synthetase
      in a model of acute sepsis. Our results show that animals treated with bacterial
      lipopolysaccharide experience a marked decrease in liver SAM synthetase activity.
      No changes were detected in the hepatic levels of SAM synthetase protein,
      suggesting that inactivation of the existing enzyme was the cause of the observed
      activity loss. Lipopolysaccharide treatment resulted in the expression of calcium
      independent/cytokine-inducible nitric oxide (NO) synthase in liver and the
      accumulation in plasma of the NO-derived species nitrite and nitrate. NO
      implication in the in vivo regulation of SAM synthetase was evaluated in animals
      treated with the NO donor molecule 3-morpholinosydnonimine. The analysis of liver
      enzymatic activity, along with protein and messenger RNA levels yielded results
      similar to those obtained with lipopolysaccharide treatment. To assess directly
      the sensitivity of SAM synthetase to NO, the rat liver-purified high- and low
      molecular weight forms of the enzyme were exposed to various doses of 3
      morpholinosydnonimine and other NO donors such as S-nitroso-N
      acetylpenicillamine, resulting in a dose-dependent inhibition of enzymatic
      activity. This effect was reversed by addition of the reducing agents beta
      mercaptoethanol and glutathione. Finally, cysteine 121 was identified as the site
      of molecular interaction between NO and rat liver SAM synthetase that is
      responsible for the inhibition of the enzyme. To reach this conclusion, the 10
      cysteine residues of the enzyme were changed to serine by site-directed
      mutagenesis, and the effect of NO on the various recombinant enzymes was
      measured.

PMID- 9021953
TI  - Relative impact of HLA phenotype and CD4-CD8 ratios on the clinical expression of
      hemochromatosis.
AB  - Hemochromatosis is a hereditary iron-overload disease linked to HLA. The clinical
      expression of hemochromatosis is influenced by sex and age. However, other
      factors must account for the notorious heterogeneity of expression of the disease
      independent of sex, age, and HLA phenotype. The present study attempts to clarify
      some of these additional factors based on exhaustive statistical analysis of data
      collected from 43 selected patients with hemochromatosis. The statistical
      analysis focused on three groups of variables: the first group included variables
      reflecting the clinical expression of the disease; the second group represented
      the biochemical and hematological values at the time of diagnosis; and the third
      group consisted of the independent variables sex, age, HLA phenotype, and T-cell
      subset profile, i.e., the percentages and total numbers of CD4+ and CD8+ cells
      and the CD4-CD8 ratios. The results show that the relative expansion of the two
      main T-cell subsets, in the context of the HLA phenotype, correlates
      significantly with the clinical expression of hemochromatosis and the severity of
      iron overload. The present findings substantiate further the postulate that T
      cells have a role in the regulation of iron metabolism.

PMID- 9021954
TI  - Characterization of a swelling-activated anion conductance in homozygous typing
      cell hepatoma cells.
AB  - Liver cell volume and intracellular ion concentrations are maintained within a
      narrow physiologic range by regulated changes in membrane ion permeability. These
      studies of homozygous HTC hepatoma cells, a model liver cell line, evaluate the
      relationship between cell volume and membrane ion permeability, and assess the
      possibility that cell swelling allows the efflux of the intracellular osmolite
      taurine through the opening of a conductive pathway. Cell swelling induced by
      exposure to hypotonic solutions (203 mOsm) caused a rapid increase in cell
      volume, followed by recovery toward basal values. Volume recovery was inhibited
      by Cl- depletion or by exposure to the putative Cl- channel blocker 5-nitro-2-(3
      phenylpropyl-amino) benzoic acid (NPPB) (25 micromol/L). Swelling increased the
      efflux rates of 36Cl (181% +/- 15%, P < .01) and 125I (310% +/- 21%, P < .01). In
      whole cell patch clamp recordings, cell swelling induced by 1) exposure to
      hypotonic solution or 2) intracellular perfusion with hypertonic sucrose
      containing solutions activated an anion-selective current which was outwardly
      rectified and showed time-dependent inactivation at depolarizing potentials. The
      current density at -80 mV increased proportionally with increases in the
      transmembrane osmotic gradient from basal values of -1 pA/pF to maximal values of
      70 pA/pF with 100 mmol/L sucrose in the pipette. Basal taurine permeability was
      low, but cell swelling increased the efflux of [1,2-3H]taurine to 1,587% +/- 172%
      of basal levels (P < .05). Intracellular perfusion with hypertonic solutions
      activated currents carried by anionic taurine, with an estimated taurine/Cl-
      permeability ratio of .88 +/- .17 for whole cell currents. These studies
      demonstrate that the HTC membrane anion permeability is closely coupled to
      changes in cell volume, and that the recovery from swelling depends upon
      activation of anion-selective conductance pathways permeable to both Cl- and
      taurine.

PMID- 9021955
TI  - The in vivo effect of hepatotrophic factors augmenter of liver regeneration,
      hepatocyte growth factor, and insulin-like growth factor-II on liver natural
      killer cell functions.
AB  - Fine balanced sequential changes of the levels of circulating hepatotrophic
      factors are essential for normal liver regeneration. Our recent studies have
      indicated that liver-resident natural killer (NK) cells are important regulators
      of liver regeneration and have raised the possibility that hepatotrophic factors
      might mediate their activities through NK cells. In the present study, we
      assessed the effects of in vivo administration of three hepatotrophic factors
      (augmenter of liver regeneration [ALR], insulin-like growth factor-II [IGF-II],
      and hepatocyte growth factor [HGF]) on NK cells in normal rats. Each of the
      three, given over a 1-day period in doses known to produce hepatotrophic
      activity, induced inhibition of NK cell cytotoxic activities in the population of
      mononuclear leukocytes (MNL) in the liver, but not in MNL from the spleen or
      peripheral blood. In contrast to these results obtained by the whole animal
      treatment, the three molecules had no effect on NK cell functions when added to
      cultures of MNL from the livers, spleens, or blood of untreated rats. These data
      support and extend our previously advanced hypothesis that ALR and other
      hepatotrophic factors play an important role in liver regeneration by regional
      regulation of NK cells through some as-yet-unknown intermediary mechanism.

PMID- 9021956
TI  - The anti-inflammatory drug sodium salicylate inhibits nitric oxide formation
      induced by interleukin-1beta at a translational step, but not at a
      transcriptional step, in hepatocytes.
AB  - Recent evidence suggests that nitric oxide (NO) mediates cellular injury under
      the pathological conditions such as endotoxemia in the liver of rats. Regulation
      of NO production is crucial for improving the hepatic dysfunction. We have
      previously reported that, in cultured rat hepatocytes, a single cytokine
      interleukin-1beta (IL-1beta) stimulated a release of nitrite, an oxidation
      product of NO, into culture medium dose- and time-dependently. The objective of
      this study was to investigate an ability of the anti-inflammatory drug NaSA to
      affect the production of NO in hepatocytes. IL-1beta increased levels of
      inducible NO synthase (iNOS) messenger RNA (mRNA) with a maximal effect at 8
      hours in primary cultures of rat hepatocytes. Nuclear factor-kappaB (NF-kappaB),
      that is an important nuclear factor protein in iNOS gene transcription in
      response to inflammatory mediators, also appeared in the nuclear fraction of
      hepatocytes 1 hour after addition of IL-1beta. Sodium salicylate markedly
      inhibited the NO formation induced by IL-1beta, but did not affect NF-kappaB
      activation and iNOS mRNA induction. Western blot analysis revealed that sodium
      salicylate (NaSA) blocked a step of iNOS protein synthesis. These findings
      indicate that NaSA may reduce hepatic injury by preventing the induction of NO
      formation in response to IL-1beta at the posttranscriptional step.

PMID- 9021957
TI  - Assessment of the longevity of the liver using a rat transplant model.
AB  - To assess the longevity of the liver, arterialized, orthotopic liver grafts were
      performed using syngeneic male BN/BiRij rats. Young (5-month-old) livers were
      transplanted into 5-month-old recipients (group I, n = 27), and old (28-month
      old) livers were transplanted into 5-month-old rats (group II, n = 28). Recipient
      survival after transplantation was similar in both groups. The average age of the
      livers at the time of death was 16.7 months in group I and 39.1 months in group
      II. Four of the livers in group II survived for more than 4 years (48.1 to 52.4
      months). Early deaths (less than 1 year) after transplantation were most commonly
      caused by biliary obstruction and cholangitis in both groups. Late deaths (more
      than 1 year) after grafting were mainly from heart failure or tumors. None of the
      animals died of liver failure or liver disease. Weight gain in the rats, total
      serum protein levels, and alanine transaminase levels after transplantation did
      not differ significantly between the two groups. There was a trend for the
      histological features of aging of the liver-fibrosis, bile duct proliferation,
      and pigment deposition-to become more prevalent as the livers became very old
      (mean age, 46 months). Nevertheless, typical aging changes, as individual
      findings, were absent in nearly half of the oldest organs. The alterations in
      morphology had no apparent effect on the ability of the livers to sustain the
      lives of the recipients. The liver of the BN/BiRij rat was capable of surviving
      far beyond the maximum life span of BN/BiRij rats, and rats in general. It did
      not become diseased in the process.

PMID- 9021958
TI  - Preoperative determination of the surgical procedure for hepatectomy using
      technetium-99m-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy.
AB  - Technetium-99m-diethylenetriaminepentaacetic acidgalactosyl human serum albumin
      (Tc-GSA) is a new liver scintigraphy agent which binds to the asialoglycoprotein
      receptors. We evaluated the preoperative assessment for hepatectomy using Tc-GSA
      liver scintigraphy. Ninety patients with hepatocellular carcinoma were admitted
      for elective hepatectomy. Tc-GSA scintigraphy was conducted after the intravenous
      injection of Tc-GSA, and maximal removal rate of Tc-GSA (GSA-Rmax) was calculated
      using a radiopharmacokinetic model. Measurement of GSA-Rmax, conventional liver
      function, and 15-minute retention rate of indocyanine green (ICGR15) was carried
      out preoperatively. The relationships between liver functions, histological
      activity index (HAI), ICGR15, and GSA-Rmax values were estimated. A significant
      correlation was obtained between GSA-Rmax and ICGR15 (r = .534, P < .0001).
      Preoperative discrepancies between GSA-Rmax and ICGR15 values were seen in 15
      patients. In these cases, the GSA-Rmax values correlated well with the total HAI
      scores (r = .595, P < .02), but no significant correlation was seen between the
      ICGR15 and HAI scores. Two patients died of postoperative liver failure within 2
      months of the operation. These two patients were found to have severe
      discrepancies between their preoperative GSA-Rmax and ICGR15 values. We concluded
      that GSA-Rmax might be useful for selecting candidates for hepatectomy and that
      extended hepatectomies (di- and tri-segmentectomy) are high-risk surgical
      procedures in the case of low GSA-Rmax scores (below 0.35).

PMID- 9021959
TI  - Nicardipine as antihypertensive therapy in liver transplant recipients: results
      of long-term use.
AB  - Arterial hypertension is frequent in liver transplant recipients on cyclosporine
      A (CsA). Nicardipine is a calcium channel blocker (CCB) that has been shown to be
      efficient in controlling postoperative hypertension. However, its use has been
      limited in organ recipients because of its reported interaction with CsA
      metabolism. In this report, we studied the results of the long-term use of
      nicardipine after liver transplantation. Forty-nine consecutive liver transplant
      recipients with a follow-up longer than 2 years were studied. Immunosuppressive
      regimen was based on CsA and prednisone. Patients with immediate postoperative
      hypertension received intravenous nicardipine, secondarily switched to oral
      nicardipine (group 1, n = 27). Patients with delayed hypertension (i.e., >2 weeks
      posttransplant) received other antihypertensive drugs which did not interact with
      CsA metabolism. These patients and those without hypertension formed group 2 (n =
      22). The two groups were similar for age, sex, body weight, and transplantation
      indications. Interaction of nicardipine with CsA metabolism was confirmed.
      Whereas cyclosporine blood levels were similar in both groups at any time during
      the study, the mean cyclosporine daily dose required to achieve such levels was
      30% lower in group 1 compared with group 2 (P < .01). This resulted in a
      significant cost-containment. The use of nicardipine was not associated with an
      increased incidence of graft rejection or CsA toxicity episodes. The results in
      liver transplant recipients showed that nicardipine interacts with CsA
      metabolism, leading to a 30% reduction in CsA dose and does not increase the risk
      of CsA toxicity or graft rejection. Nicardipine can be used safely for the
      treatment of arterial hypertension after liver transplantation with a potential
      cost-containment.

PMID- 9021960
TI  - Fulminant hepatitis B virus: recurrence after liver transplantation in two
      patients also infected with hepatitis delta virus.
AB  - Liver transplantation for hepatitis B virus (HBV)-related liver disease is
      complicated by HBV recurrence and, consequently, poor patient and graft survival.
      Patients transplanted for hepatitis delta virus (HDV)-related cirrhosis are
      reported to have a diminished incidence of HBV recurrence and improved graft
      survival. However, only a few reported HDV-infected patients had active HBV
      replicative disease before liver transplantation. In our experience, we
      transplanted two HDV-infected patients, both of whom had active HBV replication
      before liver transplantation. In one patient, hepatitis B surface antigen (HBsAg)
      recurred four months after transplantation. Two months later, Hepatitis Be
      antigen (HBeAg) and HBV-DNA became positive, and the patient died of fulminant
      recurrent hepatitis B and hepatitis delta. In the other patient, HBV persisted
      after transplantation, and 2 months later the patient required retransplantation
      for fulminant recurrent hepatitis B and hepatitis delta. With the second graft,
      the patient remained free of HBV infection for 1 year. Thereafter, the patient
      experienced HBV recurrence with active replication and died of fulminant
      hepatitis B and delta recurrence. In the first case and in the second graft of
      the second case, hepatitis B immunoglobulin (HBIG) immunoprophylaxis was
      administered in an attempt to prevent recurrence of HBV. The literature suggests
      that an HDV infection inhibits the replication of HBV and therefore plays a role
      in preventing the recurrence of HBV and improving survival. Our experience with
      two patients suggests that HDV infection, in the presence of active HBV
      replication, may not play a protective role.

PMID- 9021961
TI  - Relation of disease activity during chronic hepatitis C infection to complexity
      of hypervariable region 1 quasispecies.
AB  - We studied the heterogeneity in the E2/NS1 hypervariable region 1 of the
      hepatitis C virus (HCV) genome in relation to the natural course after infection.
      The subjects were composed of 38 chronic hepatitis C carriers who had been
      followed for 9 to 218 months after the onset of non-A, non-B (type C) hepatitis,
      being tested monthly for serum alanine aminotransferase levels. The complexity of
      the sequence heterogeneity was assessed by single-strand conformation
      polymorphism analysis. The quasispecies complexity had no relation to the route
      of infection, the time from infection and the duration of aminotransferase
      elevation after the onset. However, it had a significant relationship with the
      degree of aminotransferase elevation in the course of the disease. The
      quasispecies complexity was directly correlated with the first peak of serum
      aminotransferase at the onset (r = .48, P < .01) and the mean aminotransferase
      levels during the period of persistent aminotransferase elevation (r = .58, P <
      .01). Twenty-three of the 38 patients were further followed for 24 months with
      biweekly alanine transaminase (ALT) tests. Their aminotransferase levels remained
      within the normal range during follow-up, and no significant change was seen in
      the quasispecies complexity after this asymptomatic period. However among the 23
      patients, the quasispecies complexity increased in six cases (26%) and decreased
      in five (22%). A significant direct relation was seen between changes in the
      quasispecies complexity and the mean aminotransferase levels during the
      asymptomatic period (r = .55, P = .01). These findings suggest that the
      development of the HCV quasispecies nature may be related to the severity of the
      hepatitis in the course of infection.

PMID- 9021962
TI  - Treatment of chronic hepatitis C with interferon alfa-n3: a multicenter,
      randomized, open-label trial.
AB  - We studied the antiviral effectiveness and safety of interferon alfa-n3, a
      natural alpha interferon which contains multiple interferon species, in the
      treatment of previously untreated patients with chronic hepatitis C. Seventy
      seven patients were randomized to receive either 1.0, 2.5, 5.0, or 10.0 million
      units (MU) of interferon alfa-n3 three times a week for 24 weeks and were then
      followed for an additional 24 weeks. At the end of therapy, 67% of patients in
      the 10 MU group normalized serum alanine transaminase (ALT) levels and 59% had no
      hepatitis C virus (HCV) RNA detected by polymerase chain reaction. At the end of
      the follow-up period, 44% of patients in the 10 MU group maintained normal ALT,
      and 24% had nondetectable HCV RNA. Lower doses were much less effective.
      Interferon alfa-n3 was well tolerated and no patient developed neutralizing anti
      interferon antibodies during or after the treatment period. Interferon alfa-n3
      appears to be effective against hepatitis C virus and deserves further study in
      larger randomized controlled trials.

PMID- 9021963
TI  - Detection of type 2-like T-helper cells in hepatitis C virus infection:
      implications for hepatitis C virus chronicity.
AB  - One striking clinical feature of hepatitis C virus (HCV) infection is that more
      than 50% of patients with acute hepatitis C will develop chronic infection. To
      investigate its possible mechanisms, we examined the activation of type 2-like T
      helper (Th2-like) cells relating to the development of chronicity. Peripheral
      blood CD4+ T-cell proliferation and cytokine secretion in response to a panel of
      recombinant HCV antigens including core (C22), envelope 1 (E1), E2, nonstructural
      (NS) protein 4 (C100), fusion protein of NS3 and NS4 (C200), and NS5 were assayed
      in 17 patients with acute hepatitis C. All six patients with self-limited disease
      had a significant CD4+ T-cell proliferation to C22, E1, C100, C200, and NS5,
      running parallel with the antigen-stimulated secretion of interleukin (IL)-2 and
      interferon gamma (IFN-gamma), but not with interleukin (IL)-4 and IL-10,
      indicating predominant Th1 responses. Among the remaining 11 patients who
      developed chronicity, 6, 2, and 9 cases showed a specific CD4+ T-cell response to
      C22, C100, and C200, respectively, and the responses were significantly lower
      than those of cases with recovery in terms of stimulation index (SI) (P < .05)
      and of antigen-stimulated IL-2 and IFN-gamma production. Importantly, IL-4 and IL
      10 (Th2 responses) were detectable, and C22-specific Th2-like T-cell clones could
      be generated from patients with chronicity. The data suggested that activation of
      Th2 responses in acute hepatitis C patients may play a role in the development of
      chronicity.

PMID- 9021964
TI  - A specific antibody response to HCV E2 elicited in mice by intramuscular
      inoculation of plasmid DNA containing coding sequences for E2.
AB  - As the chimpanzee, the only reliable animal model for hepatitis C virus (HCV)
      infection, is impractical for early stage testing of HCV vaccine candidates, we
      have evaluated the immune response in mice to an experimental plasmid based HCV
      vaccine. We used this system because DNA vaccines can be rapidly constructed
      without the necessity of large scale protein production and purification. In this
      preliminary study we tested the immune response in mice to HCV envelope
      glycoprotein, E2, induced by a eukaryotic expression plasmid. Protein expression
      was monitored by immunofluorescence in transfected tissue culture cells. Each
      mouse was inoculated intramuscular with 100 microg plasmid DNA and some mice were
      boosted after 5 weeks. Among 12 BALB/C mice inoculated, 10 developed antibody to
      E2 by the second week. The antibody levels increased steadily before reaching a
      plateau in mice receiving the booster, but in the nonboosted mice the antibody
      declined over time. The serum from one mouse was tested against a series of
      overlapping peptides covering most of E2. This serum contained antibodies
      recognizing two distinct epitopes beginning at amino acid 57 and amino acid 113
      but no antibody was directed against peptides representing the hypervariable
      region of E2, antibody to which is thought to be important in HCV neutralization.
      We have shown that the use of plasmid based vaccines can induce a specific immune
      response in mice against HCV antigens. This system should be useful as the first
      step in vaccine development.

PMID- 9021965
TI  - Demonstration of duck hepatitis B virus in bile duct epithelial cells:
      implications for pathogenesis and persistent infection.
AB  - Hepatitis B virus (HBV) has been demonstrated in bile duct epithelial cells
      (BDEC) during chronic infection. The persistence of virus in BDEC may play an
      important role in disease pathogenesis, and may be at least partly responsible
      for the relapse phenomenon observed in antiviral treatments using nucleoside
      analogues. The aims of this study were to examine the morphological changes
      within the liver in the duck hepatitis B model following bile duct ligation
      (BDL), and to assess the effect of biliary hyperplasia upon viral DNA and
      proteins. Seven-day-old ducklings, congenitally infected with the duck hepatitis
      B virus (DHBV), were subject to BDL. The pathological and virological changes
      were then followed at 5, 10, 15, and 20 days after ligation. All results were
      compared with age-matched unligated control birds congenitally infected with
      DHBV. To assess the early morphological changes, additional animals were
      sacrificed at 1, 2, 3, and 4 days post-BDL. The proportion of DHBV-infected BDEC,
      was examined by immunohistochemistry and in situ hybridization. BDL induced rapid
      biliary hyperplasia, with a doubling time for BDEC of 1.3 days. The proliferated
      BDEC displayed immunohistochemical features identical to resting BDEC. More than
      50% of BDEC in unligated controls, and more than 46% of proliferated BDEC in
      ligated animals were positive for DHBV DNA and structural proteins. The intensity
      of immunohistochemical staining and in situ hybridization signal in the BDEC was
      consistently greater than that of the hepatocytes, both before and after BDL. BDL
      induces biliary hyperplasia in the duck model, and BDEC division does not reduce
      the viral burden in infected cells.

PMID- 9021966
TI  - Induction of cytotoxic T-cell response against hepatitis C virus structural
      antigens using a defective recombinant adenovirus.
AB  - A replication-defective recombinant adenovirus (RAd), RAdCMV-CE1, containing core
      and E1 genes of hepatitis C virus (HCV) was constructed. RAdCMV-CE1 was able to
      express core and E1 proteins both in mice and human cells. Immunization of BALB/c
      mice with RAdCMV-CE1 induced a specific cytotoxic T-cell response against the two
      HCV proteins. This response was characterized using a panel of 60 synthetic 14-
      or 15-mer overlapping peptides (10 amino-acid overlap) spanning the entire
      sequence of these proteins. Five main epitopes were found in the core protein,
      four of which had been previously described either in mice or humans. One single
      novel epitope was found in E1. Fine mapping of this E1 determinant, showed that
      octamer GHRMAWDM is the minimal epitope recognized by cytotoxic T lymphocytes
      (CTL). The cytotoxic T-cell response was H-2d restricted, lasted for at least 100
      days, and was mediated by T cells with the classic CD4-CD8+ phenotype. This work
      demonstrates that replication-defective recombinant adenoviruses can efficiently
      express HCV proteins and are able to induce an in vivo cytotoxic T-cell response
      against a diversity of epitopes from HCV antigens. These vectors should be taken
      into consideration in the design of vaccines and also as a means to stimulate
      specific T-cell responses in chronic HCV carriers.

PMID- 9021967
TI  - Acute sporadic non-A, non-B, non-C, non-D, non-D, non-E hepatitis.
AB  - Patients presenting with clinical and laboratory features consistent with a
      diagnosis of acute non-A, non-B hepatitis were evaluated for evidence of
      hepatitis C or hepatitis E infection and for evidence of severe or prolonged
      disease. Antibody to hepatitis C virus (anti-HCV) was detected in 75 of 108 (69%)
      patients, antibody to hepatitis E virus (anti-HEV) in three patients (3%), and
      neither antibody in 31 (29%) patients. One patient had both anti-HCV and anti
      HEV. HCV RNA was not detected in sera from any of 20 patients with seronegative
      (non-ABCDE) hepatitis, but in all 10 patients with anti-HCV who were tested by
      polymerase chain reaction (PCR). Compared with patients with acute hepatitis C,
      those with non-ABCDE hepatitis had a lower incidence of parenteral risk factors
      (6% vs. 70%; P < .001), higher peak serum bilirubin levels (45% vs. 5% with peak
      levels > 15 mg/dL; P < .001), more prolonged jaundice (25% vs. 0% with peak
      bilirubin >5 weeks after onset; P < .01), more severe prothrombin time
      abnormalities (26% vs. 0% with >3 second prolongation; P < .001), more severe
      hypoalbuminemia (39% vs. 9% with albumin <3 g/dL; P < .01), and more frequent
      major clinical complications (13% vs. 0% with encephalopathy; P < .01; 10% vs. 0%
      with death or transplant; P = .024). Patients with acute non-ABCDE hepatitis were
      less likely to develop chronic hepatitis than those with acute hepatitis C (23%
      vs. 68%; P < .05). Thus, patients with acute non-ABCDE hepatitis are
      epidemiologically distinct from those with acute hepatitis C and have a
      significantly more severe acute illness.

PMID- 9021968
TI  - Hepatic drug delivery and gene therapy.
AB  - On September 21-22, 1995, an international meeting entitled "Targeting of Novel
      Therapeutics to the Liver and GI Tract" was held at the Natcher Conference Center
      on the campus of the National Institutes of Health. The conference was sponsored
      by the National Institute of Diabetes and Digestive and Kidney Diseases through
      the Division of Digestive Diseases and Nutrition and Digestive Diseases
      Interagency Coordinating Committee (DDICC). Section 440A of Public Law 94-562 in
      1976 created the DDICC for the purpose of coordinating the digestive disease
      related research activities of relevant federal health agencies into a
      coordinated program aimed at combating digestive diseases. As part of this
      federal effort, an assessment of the "state of the art" for targeted drug
      therapeutics to the liver and gene therapy was undertaken through the conference,
      cochaired by Dr. Mark Zern (Thomas Jefferson Medical College) and Dr. Flossie
      Wong-Staal (University of California, San Diego, CA). The conference was divided
      into four sessions: Session I was Vectors and Techniques; Session II was Liver
      and Metabolic Diseases; Session III was Hepatitis and GI Disease; and Session IV
      was Approaches for HIV Infection. This summary focuses on the new technologies
      and the studies directly pertaining to liver disease. Table 1 lists the
      techniques and their applications. Table 2 describes viral vectors that have been
      employed for the purpose of hepatic gene therapy. Table 3 summarizes the studies
      presented as posters at the conference.

PMID- 9021969
TI  - Is fatigue associated with cholestasis mediated by altered central
      neurotransmission?

PMID- 9021970
TI  - Hemochromatosis and "HLA-H": definite!
AB  - BACKGROUND/AIMS: Hereditary hemochromatosis (HH), which affects some 1 in 400 and
      has an estimated carrier frequency of 1 in 10 individuals of Northern European
      descent, results in multi-organ dysfunction caused by increased iron deposition,
      and is treatable if detected early. Using linkage-disequilibrium and full
      haplotype analysis, we have identified a 250kb region more than 3 megabases
      telomeric of the major histocompatibility complex (MHC) that is identical-by
      descent in 85% of patient chromosomes. Within this region, we have identified a
      gene related to the MHC class I family, termed HLA-H, containing two missense
      alterations. One of these is predicted to inactivate this class of proteins and
      was found homozygous in 83% of 178 patients. A role of this gene in
      hemochromatosis is supported by the frequency and nature of the major mutation
      and prior studies implicating MHC class I-like proteins in iron metabolism.

PMID- 9021971
TI  - The hepatitis B virus X protein: the quest for a role in viral replication and
      pathogenesis.
AB  - Although the biological importance of hepatitis B virus X protein (HBX) in the
      life cycle of hepatitis B virus has been well established, the cellular and
      molecular basis of its function remains largely undefined. Despite the
      association of multiple activities with HBX, none of them appear to provide a
      unifying hypothesis regarding the true biological function of HBX. Identification
      and characterization of cellular targets of HBX remain an essential goal in the
      elucidation of the molecular mechanisms of HBX. Using the Saccharomyces
      cerevisiae two-hybrid system, we have identified and characterized a novel
      subunit of the proteasome complex (XAPC7) that interacts specifically with HBX.
      We also showed that HBX binds specifically to XAPC7 in vitro. Mutagenesis studies
      have defined the domains of interaction to be critical for the function of HBX.
      Furthermore, overexpression of XAPC7 appeared to activate transcription by itself
      and antisense expression of XAPC7 was able to block transactivation by HBX.
      Therefore, the proteasome complex is possibly a functional target of HBX in
      cells.

PMID- 9021972
TI  - Biliary excretion of 400- to 1,000-d polyethylene glycol will influence the
      calculation of small intestinal absorption in portacaval-shunted rats.

PMID- 9021973
TI  - Antipyrine clearance and response to interferon therapy in chronic hepatitis.

PMID- 9021974
TI  - Redistribution of canalicular cell membrane enzyme in hepatocytes following their
      isolation and during early cell culture.

PMID- 9021991
TI  - Germinal center B cells rescued from apoptosis by CD40 ligation or attachment to
      follicular dendritic cells, but not by engagement of surface immunoglobulin or
      adhesion receptors, become resistant to CD95-induced apoptosis.
AB  - Germinal centers (GC) constitute a specialized microenvironment essential for the
      formation of memory B cells, B cell affinity maturation and isotype switching.
      Within the GC, the B cells closely interact with follicular dendritic cells (FDC)
      and T cells, which both provide stimuli to the B cells that prevent their entry
      into apoptosis and promote their differentiation into memory cells or plasma
      cells. Cross-linking of B cell immunoglobulin (Ig) receptors by antigen,
      stimulation of the integrin adhesion molecules LFA-1 and VLA-4 on the B cell
      through interaction with their counter receptors ICAM-1 and VCAM-1 on the FDC and
      cross-linking of CD40 on the B cells through interaction with the CD40 ligand
      (CD40L) on T cells have been shown to prevent entry into apoptosis of GC B cells.
      Triggering of CD95, on the other hand, has been shown to induce apoptosis. We
      therefore investigated the interaction between adhesion-mediated signals, Ig,
      CD40, and CD95. The spontaneous apoptosis of GC B cells was not further increased
      by adding anti-CD95. However, CD95 stimulation did result in apoptosis of GC B
      cells in the presence of anti-Ig or adhesion-mediated rescue signals, which
      indicates that CD95 expressed on GC B cells is functionally active. In contrast,
      anti-CD95 was unable to induce apoptosis in cells rescued via CD40 stimulation,
      suggesting an important role for CD40L expressed on GC T cells in apoptosis
      regulation. We also studied apoptosis of B cells adhering to FDC, and found that
      B cells that interact with FDC were also rescued from CD95-induced apoptosis. A
      human CD40.Fc mu fusion protein that blocks CD40 ligation failed to inhibit this
      effect. Our studies therefore indicate that neither CD40, Ig receptors, nor
      adhesion receptors mediate rescue from apoptosis by FDC.

PMID- 9021992
TI  - Functional relevance during lymphocyte migration and cellular localization of
      activated beta1 integrins.
AB  - The state of integrin activation can be assessed by monoclonal antibodies (mAb)
      that selectively recognize integrins in their active form. We demonstrate herein
      that the expression of the epitope recognized by mAb HUTS-21 is induced on T
      lymphoblasts upon binding of soluble vascular cell adhesion molecule (VCAM)-1 and
      an 80-kDa tryptic fragment of fibronectin (FN80) to the beta1 integrins very late
      activation antigen (VLA)-4 and VLA-5, and that this effect is dependent on ligand
      concentration and is specific for beta1 integrins. On T lymphoblasts adhering to
      immobilized fibronectin, the HUTS-21 epitope localized exclusively to sites of
      integrin binding to fibronectin. These results indicate that mAb HUTS-21
      recognizes a ligand-induced binding site (LIBS) on the common beta1 subunit of
      VLA proteins. Engagement of beta1 integrins through this LIBS epitope inhibited T
      lymphoblast movement on fibronectin, as determined by quantitative time-lapse
      video microscopy studies. Furthermore, the HUTS-21 mAb also prevented T
      lymphoblast-directed migration through gradients of substratum-immobilized beta1
      integrin ligands such as fibronectin or VCAM-1, whereas it did not affect
      migration on intercellular adhesion molecule (ICAM)-1. This anti-LIBS mAb
      stimulated cell adhesion through postreceptor events, without affecting receptor
      affinity for ligand, and appears to interfere with cell migration by a mechanism
      distinct from that of other anti-beta1 activating antibodies.

PMID- 9021993
TI  - Expression of pro-inflammatory cytokines by TCR alpha beta+ and TCR gamma delta+
      T cells in an experimental model of colitis.
AB  - An inflammatory bowel disease (IBD) comparable to human ulcerative colitis is
      induced upon transfer of T cell-depleted wild-type (F1) bone marrow into
      syngeneic T cell-deficient (tg epsilon26) mice (F1 --> tg epsilon26). Previously
      we have shown that activated CD4+ T cells predominate in transplanted tg
      epsilon26 mice, and adoptive transfer experiments verified the potential of these
      cells to cause disease in immunodeficient recipient mice. Using flow cytometry
      for the detection of intracellular cytokine expression, we demonstrate in the
      present study that large numbers of CD4+ and CD8+ TCR alphabeta+ T cells from the
      intraepithelial region and lamina propria of the colon of diseased, but not from
      disease-free mice, produced interferon-gamma (IFN-gamma) and tumor necrosis
      factor-alpha (TNF-alpha). Large numbers of T cells from peripheral lymphoid
      tissues of these animals also expressed IFN-gamma and TNF-alpha, but few
      expressed interleukin-4, demonstrating a strong bias towards Th1-type T cell
      responses in these animals. TCR gammadelta+ T cells, typically minor constituents
      of the inflammatory infiltrate of the colon in F1 --> tg epsilon26 mice, also
      expressed IFN-gamma at a high frequency upon CD3 stimulation. In light of these
      findings we examined the potential involvement of TCR gammadelta+ T cells by
      testing their ability to induce colitis in tg epsilon26 mice. We report here that
      tg epsilon26 mice transplanted with T cell-depleted bone marrow from TCR
      alpha(null) and TCR beta(null) animals developed IBD. Furthermore, disease in
      these mice correlated with the development of peripheral and colonic TCR
      gammadelta+ T cells capable of IFN-gamma production. These results suggest that
      IFN-gamma may be a common mediator of IBD utilized by pathogenic T cells of
      distinct phenotype.

PMID- 9021994
TI  - Split activity of interleukin-10 on antigen capture and antigen presentation by
      human dendritic cells: definition of a maturative step.
AB  - Human CD1+ CD14- dendritic cells (DC) can be derived from CD14+ monocytes using
      granulocyte/monocyte colony-stimulating factor and interleukin (IL)-4. We have
      previously shown that IL-10 pre-treatment of such DC significantly inhibited
      their antigen-presenting capacity to CD4+ T cell clones. In this study, we
      further analyze how IL-10 influences antigen presentation. We first investigated
      whether IL-10 could alter the early stage of antigen presentation, the capture of
      antigen. This can be mediated by mannose receptor (MR)-mediated endocytosis and
      by fluid-phase uptake through macropinocytosis. IL-10-treated DC showed an
      enhancement of both mechanisms of antigen capture, as indicated by the increase
      of fluorescein isothiocyanate-dextran uptake through MR and lucifer yellow
      uptake. However, IL-10-treated DC, irradiated or glutaraldehyde-fixed, were less
      efficient than untreated DC in stimulating mixed leukocyte reaction as well as in
      inducing the activation of peptide-specific T cell clones, indicating that IL-10
      achieves its effects mainly by modifying the cell surface phenotype of DC. HLA
      class I and II, as well as intercellular adhesion molecule (ICAM)-1, lymphocyte
      function-associated antigen-3, B7-1, B7-2 and ICAM-3 expression were either
      significantly increased or essentially unchanged, and the ability to bind the
      epitope recognized by the T cell clones was also unaffected regardless of IL-10
      treatment. Our study also indicates that as-yet unidentified accessory molecules
      may play an essential role in T cell activation. Thus, the IL-10-treated DC
      possess an increased capacity to capture antigen, with a concomitant decreased
      stimulatory activity. Our study suggests that IL-10-treated DC have the
      characteristics of highly immature DC (high capture ability, low stimulatory
      potency) and may represent an early maturative step of human DC of monocytic
      origin.

PMID- 9021995
TI  - Human T lymphocytes bind to germinal centers of human tonsils via integrin
      alpha4/VCAM-1 and LFA-1/ICAM-1 and -2.
AB  - Binding of T lymphocytes within the different compartments of the secondary
      lymphoid organs is crucial for the function of the cellular and the humoral
      immune response. It is still not known which adhesion molecules guide T cells to
      the distinct areas of the lymphoid microenvironment. In the current study an in
      situ adhesion assay was used to define the receptors for binding of T cells to
      human tonsils. The T cell lines Jurkat and MOLT-4 and normal, activated T cells
      were found to bind exclusively to germinal centers. Jurkat cells used the
      receptor pair integrin-alpha4 (VLA-4alpha)/VCAM-1, whereas activated MOLT-4 cells
      and normal T cells bound via both adhesion pathways, namely via integrin
      alpha4/VCAM-1 and LFA-1/ICAM-1 and -2. It is suggested that these adhesion
      mechanisms are involved in the migration of T cells into the germinal centers of
      secondary lymphoid organs and that they influence the selection of B cells by
      apoptosis.

PMID- 9021996
TI  - The influence of granulocyte/macrophage colony-stimulating factor on dendritic
      cell levels in mouse lymphoid organs.
AB  - To ascertain whether the development of dendritic cells (DC) in mouse lymphoid
      organs is dependent on granulocyte/macrophage colony-stimulating factor (GM-CSF),
      we determined the number of DC in the thymus, spleen and lymph nodes of normal
      mice, of mice with the genes coding for GM-CSF or its receptor inactivated, and
      of transgenic mice with excessive levels of GM-CSE DC were extracted from the
      tissues and enriched prior to flow cytometric analysis. The total DC level and
      the incidence of DC expressing lymphoid-related markers (CD8(hi) CD11b(lo)) and
      myeloid-related markers (CD8(lo) CD11b(hi)) were monitored. Both in GM-CSF null
      mice, and GM-CSF receptor null mice, DC of all surface phenotypes were present in
      all lymphoid organs; only small decreases in DC levels were recorded, except for
      the lymph nodes of GM-CSF receptor null mice which showed a more pronounced
      (threefold) decrease in DC numbers. Since the GM-CSF receptor null mice lacked
      the beta chain common to the GM-CSF, interleukin (IL)-3 and IL-5 receptors, the
      development of DC in the absence of GM-CSF was not due to common beta chain
      mediated developmental signals elicited by IL-3 or IL-5. In GM-CSF transgenic
      mice, there was only a 50 % increase in DC numbers in thymus and spleen,
      paralleling an increase in overall cellularity, but a more pronounced (threefold)
      increase in DC numbers in lymph nodes. There was no evidence that GM-CSF had a
      selective effect on any particular DC subpopulation defined by CD8 or CD11b
      expression. We conclude that the development of most lymphoid tissue DC can
      proceed in the absence of GM-CSF, although this cytokine can produce some
      elevation of DC levels. It is not clear whether the enhancing effect of GM-CSF is
      direct or an indirect effect mediated by other cytokines.

PMID- 9021997
TI  - Interferon-gamma rescues HLA class Ia cell surface expression in term villous
      trophoblast cells by inducing synthesis of TAP proteins.
AB  - Human placental trophoblast cells that constitute the materno-fetal interface
      during pregnancy escape maternal alloimmune attack. The different trophoblast
      cell subpopulations have developed efficient regulatory mechanisms to prevent
      expression of beta2-microglobulin-associated HLA class Ia molecules at their cell
      surface. We previously reported the presence of HLA class Ia messages in villous
      cytotrophoblast cells and in the syncytiotrophoblast differentiated in vitro
      purified from term placenta. In this study, we found that these transcripts are
      translated in heavy chain proteins that are endoglycosidase H sensitive and thus
      retained in the endoplasmic reticulum or cis-Golgi. Moreover, these class Ia
      heavy chains can be co-immunoprecipitated with the chaperone protein calnexin
      resident in the endoplasmic reticulum. When these trophoblast cells are treated
      with interferon (IFN)-gamma, part of the class Ia heavy chains become
      endoglycosidase H resistant, demonstrating that they have left the endoplasmic
      reticulum. Furthermore, after such a treatment, these heavy chains are detectable
      at the cell surface of these trophoblast cells, as assessed by two-color flow
      cytometry analysis and immunoprecipitation of cell surface biotinylated proteins
      using the W6/32 anti-HLA class I monoclonal antibody (mAb). IFN-gamma treatment
      induces a significant enhancement of the transcription of transporters associated
      with antigen processing (TAP1 and TAP2) rather than an increase of HLA class I or
      beta2-microglobulin messages. Finally, we demonstrate that an anti-TAP1 mAb co
      immunoprecipitates TAP1 proteins and HLA class Ia heavy chains in these IFN-gamma
      treated trophoblast cells. Thus, the constitutive absence of HLA class Ia cell
      surface expression in term villous cytotrophoblast and syncytiotrophoblast is
      likely to be due to a lack of transporter proteins that participate in the proper
      assembly of these molecules in the endoplasmic reticulum. Such a defect can be
      modified upon IFN-gamma treatment.

PMID- 9021998
TI  - Co-receptor-independent signal transduction in a mismatched CD8+ major
      histocompatibility complex class II-specific allogeneic cytotoxic T lymphocyte.
AB  - The contribution of co-receptors in signal transduction upon T cell receptor
      (TCR)-mediated recognition of major histocompatibility complex (MHC) class II
      antigen by mature T lymphocytes expressing TCR derived from the apparently co
      receptor-independent, I-Ak-specific allogeneic CD8+ CTL clone QM11 has been
      examined. Mature double-negative, CD8+ and CD4+ bulk T cell lines and clones
      expressing TCR(QM11) were developed from TCR(QM11) transgenic mice. All these T
      cells, irrespective of co-receptor expression, showed specific lytic activity on
      cells expressing I-Ak. Furthermore, co-receptorless mutants were obtained from a
      CD4+ and CD8+ clone. The responses of these co-receptorless mutants upon specific
      recognition of the alloantigen, as judged by cytolytic activity, granule
      exocytosis, lymphokine production, proliferation, and tyrosine phosphorylation of
      the zeta chain, were comparable to those of the original clones. Thus, the
      results proved the co-receptor independence of the recognition of I-Ak by
      TCR(QM11) and further indicated there is no indispensable unique signal
      transduced by co-receptors. However, when the amount of the available antigen was
      limited by anti-I-Ak antibody, the CD4+ T cell clone showed a remarkable
      resistance to the inhibition whereas the mismatched CD8+ clone was readily
      inhibitable. The anti-I-Ak-resistant component of the CD4+ clone showed
      dependency on the CD4 molecule. Taken collectively, the results indicate that the
      role played by a co-receptor molecule in mature T cells is purely quantitative
      amplification of the signal through the formation of a TCR/MHC/co-receptor
      ternary complex, and also indicate that the role of co-receptor molecules as TCR
      independent adhesion molecules is at best minimal.

PMID- 9021999
TI  - Antigen presentation by interferon-gamma-treated thyroid follicular cells
      inhibits interleukin-2 (IL-2) and supports IL-4 production by B7-dependent human
      T cells.
AB  - The consequence of recognition of antigen on antigen-presenting cells that are
      induced to express major histocompatibility complex (MHC) class II molecules
      following an inflammatory process is still not clear. In this study, we have
      investigated the outcome of antigen presentation by epithelial cells and we have
      used as a model thyroid follicular cells (TFC) that are known to express MHC
      class II molecules in autoimmune thyroid diseases and acquire the capacity to
      present autoantigens to T cells infiltrating the thyroid gland. The result show
      that MHC class II-expressing TFC were unable to stimulate a primary T cell
      alloresponse, using CD4+ T cells from three HLA-mismatched responders. Phenotypic
      analysis showed that TFC, after incubation with interferon-gamma, do not express
      the costimulatory molecules B7-1 (CD80) and -2 (CD86). Addition of murine DAP.3
      cells expressing human B7-1 (DAP.3-B7) to cultures containing peripheral blood
      CD4+ T cells and DR1-expressing TFC led to a proliferative response, suggesting
      that the failure of TFC to stimulate a primary alloresponse was due to a lack of
      co-stimulation. Similarly, HLA-DR-restricted, influenza-specific T cell clones
      dependent on B7 for co-stimulation did not respond to peptide presented by TFC;
      again the lack of response could be overcome by co-culture of TFC with DAP.3-B7.
      Furthermore, recognition of antigen on TFC inhibited interleukin-2 (IL-2)
      production in the B7-dependent T cells. In contrast, in T helper type 0 (Th0) T
      cells, IL-4 release was not affected by TFC presentation. In addition, antigen
      presentation by TFC favored IL-4 production relative to IL-2 production by B7
      independent Th0 clones. These results suggest that antigen presentation by MHC
      class II+ TFC may induce tolerance in autoreactive Th1 cells but may
      simultaneously favors a Th2 response in uncommitted T cells, and thereby support
      autoantibody production.

PMID- 9022000
TI  - The cytoplasmic domain of rat NKR-P1 receptor interacts with the N-terminal
      domain of p56(lck) via cysteine residues.
AB  - NKR-P1 is a type II transmembrane protein which acts as an activation receptor on
      natural killer (NK) cells. The cytoplasmic domains of the CD4, CD8 and 4-1BB
      receptors contain the sequence Cys-X-Cys-Pro which is directly involved in
      coupling to another pair of cysteines in the N-terminal domain of the src family
      tyrosine kinase p56(lck). The cytoplasmic domain of NKR-P1 in rodents also
      contains the Cys-X-Cys-Pro sequence, but the capacity of the receptor to bind
      p56(lck) is presently unknown. We tested for direct coupling between these
      proteins using both protein biochemistry and the yeast two-hybrid technique.
      Immunoprecipitation studies showed that p56(lck) can be co-immunoprecipitated
      with NKR-P1 from a rat NK tumor cell line. In addition, the cytoplasmic domain of
      NKR-P1 interacted with the N-terminal domain of p56(lck) in yeast as assessed by
      reporter gene activation. Integrity of the cysteine pairs in both proteins was
      critical in mediating the interaction. The experiments suggest that the
      association of p56(lck) with NKR-P1 is somewhat weaker than the p56(lck)
      association with CD8alpha, but of much lower avidity than between CD4 and
      p56(lck). This could reflect a higher activation threshold for the NKR-P1 and CD8
      receptors, which are involved in cytolytic responses, compared to CD4 which is
      involved in T cell helper function.

PMID- 9022001
TI  - Integrin alpha chain cytoplasmic tails regulate "antibody-redirected" cell
      adhesion, independently of ligand binding.
AB  - Here we describe a novel "antibody-redirected cell adhesion" (ARCA) assay. This
      assay measures heterotypic cell-cell adhesion, resulting from antibody bridging
      between Fc gamma receptors type II (CD32) on leukocytes, and clustered integrins
      on adherent cell monolayers. This ARCA activity, facilitated by integrins alpha3
      beta1 or alpha4 beta1, required an intact cytoskeleton, but did not involve
      typical integrin ligand binding sites or divalent cations. Furthermore, deletion
      of the alpha4 cytoplasmic tail almost completely abrogated integrin ARCA
      activity, suggesting an alteration of integrin recruitment into adhesive sites.
      If two or more tail residues were present after the conserved GFFKR motif, then
      ARCA activity was largely restored. Although alpha4 tail deletion caused loss of
      ARCA activity, it had no effect on the binding of VCAM-1 to intact alpha4
      transfected K562 cells. In conclusion, the integrin alpha chain tail can
      positively regulate integrin-dependent cell adhesion by a receptor
      recruitment/clustering mechanism independent of conventional integrin ligand
      binding considerations.

PMID- 9022002
TI  - Cyclophosphamide-induced blood and tissue eosinophilia in contact sensitivity:
      mechanism of hapten-induced eosinophil recruitment into the skin.
AB  - The mechanism leading to selective production and accumulation of eosinophils in
      certain allergic skin diseases is unknown. Cyclophosphamide treatment (150 mg/kg)
      of BALB/c mice 48 h before sensitization with picryl chloride (PCl) resulted in
      striking blood and tissue eosinophilia, maximal at 13 days. Blood eosinophilia
      was not induced by the sensitization with oxazolone and 2,4-dinitrofluorobenzene.
      Challenge with 1 % PCl, but not croton oil caused preferential eosinophil
      accumulation into the dermis, which was associated with the enhanced expression
      of vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells. Intravenous
      administration of anti-VCAM-1 monoclonal antibody abrogated eosinophil
      infiltration. In this murine model, we examined the role of several cytokines,
      including chemokines in inducing selective tissue eosinophilia in vivo. Local
      administration of antibodies against interleukin (IL)-1beta, IL-4, tumor necrosis
      factor (TNF)-alpha, and RANTES, but not against IL-5 before challenge inhibited
      hapten-induced eosinophil recruitment. Intradermal injection of recombinant (r)IL
      1beta, rIL-4, rTNF-alpha, rRANTES, and rMIP-1alpha induced marked eosinophil
      accumulation. Nonetheless, intradermal rIL-5 was not a chemoattractant for
      eosinophils in vivo. Our findings suggest that IL-1beta, IL-4, TNF-alpha, and
      RANTES contribute to the selective accumulation of eosinophils in contact
      sensitivity reaction. Although circulating IL-5 can activate eosinophils and
      prolong their survival, locally secreted IL-5 is not crucial for inducing
      eosinophil recruitment into the skin.

PMID- 9022003
TI  - V alpha domain modulates the multiple topologies of mouse T cell receptor V
      beta20/staphylococcal enterotoxins A and E complexes.
AB  - The superantigens staphylococcal enterotoxin A and E (SEA and SEE) both contact
      major histocompatibility complex (MHC) class II molecules on two sites located on
      the alpha and beta chains. We have investigated the role of the T cell receptor
      (TCR) alpha chain in the modulation of the various topologies of TCR/SEA (or
      SEE)/class II complexes. For this purpose, we have used three mouse V beta20 T
      cell lines expressing different V alpha domains and two T cell hybridomas
      expressing mouse V beta1 or V beta11 segments. The response of these T cells to
      SEA and SEE was studied in the context of presentation by wild-type human MHC
      class II molecules; or by mutants on MHC, in each of the two superantigen binding
      sites (position alpha39K and beta81H) to which the superantigens can still bind
      but with an altered conformation. Although V beta20 T cell lines are efficiently
      stimulated using SEA and SEE presented by wild-type HLA-DR1 molecules, our
      results show that the nature of the TCR V alpha domain can affect differently the
      recognition of the toxins bound to mutant class II molecules. This suggests that
      various functional topologies exist for both SEA and SEE/class II complexes and
      that the T cell response to each of these complexes can be modulated by the V
      alpha domain of the TCR. Interestingly, the recognition of SEA and SEE is
      achieved in different fashions by a given V beta20 T cell line.

PMID- 9022004
TI  - A transgenic T cell receptor restores thymocyte differentiation in interleukin-7
      receptor alpha chain-deficient mice.
AB  - Interleukin-7 (IL-7) receptor alpha chain-deficient (IL-7R alpha-/-) mice have
      severely depleted lymphocyte populations and thymocyte development is arrested at
      the double-negative (DN) stage. We show that thymocyte development in these mice
      can be reconstituted by the introduction of a transgenic T cell receptor (TCR),
      implying that one function of the IL-7R alpha chain is to initiate TCR gene
      rearrangement. Expression of the recombinase-activating genes RAG1 and RAG2 was
      greatly reduced in the IL-7R alpha-/- thymuses, and in DN thymocytes from the TCR
      transgenic IL-7R alpha-/- mice, but was restored in double-positive thymocytes
      from the TCR transgenic IL-7R alpha-/- mice. These data suggest that the IL-7R
      alpha chain controls RAG expression and initiation of TCR beta chain VDJ
      rearrangement in DN cells. In contrast, once cells have progressed beyond the DN
      stage of development the IL-7R alpha chain becomes no longer essential for RAG
      expression.

PMID- 9022005
TI  - A gamma delta T cell specific surface receptor (WC1) signaling G0/G1 cell cycle
      arrest.
AB  - Three monoclonal antibodies (mAb; SC-6, SC-12, and SC-29) reactive with the
      gammadelta T cell-restricted antigen WC1 were obtained immunizing mice with an
      ovine interleukin (IL)-2-dependent gammadelta T cell line. These mAb strongly
      inhibited DNA synthesis in IL-2-dependent gammadelta T cell lines with cell cycle
      arrest in G0/G1 phase, but did not induce apoptosis. The mAb-induced growth
      arrest was reversible, either by removing the mAb or by co-culture with mitogen
      or anti-CD3 in the presence of IL-2. In contrast, addition of phorbol ester,
      ionomycin and IL-2 had no effect on the mAb-induced growth arrest. The
      observations define a biologically important role for the cell surface molecule
      WC1 in the regulation of gammadelta T cell proliferation and also provide a
      suitable system to study the relevant signal transduction events.

PMID- 9022007
TI  - X-SCID B cell responses to interleukin-4 and interleukin-13 are mediated by a
      receptor complex that includes the interleukin-4 receptor alpha chain (p140) but
      not the gamma c chain.
AB  - This study investigates the effect of interleukin (IL)-4 mutant proteins and a
      monoclonal antibody to the IL-4 receptor alpha chain on IL-4 and IL-13 response
      by B cells from X-linked severe combined immunodeficiency (X-SCID) patients in
      which the common gamma chain (gamma c chain) gene mutations have been fully
      characterized and no gamma c chain expression was detected. In this gamma c chain
      gene knockout model, it was confirmed that the gamma c chain is essential for B
      cell responses to IL-2 but not for IL-4 or IL-13. Dose-response curves for X-SCID
      and normal B cell responses to IL-4 were indistinguishable, showing that the loss
      of the gamma c chain did not diminish the sensitivity of B cells to IL-4. The
      mutant protein IL-4(Y124D) and an antibody to the IL-4R alpha chain both
      inhibited responses of X-SCID B cells to IL-4 and IL-13, showing that X-SCID B
      cell responses to these cytokines are mediated by a receptor complex that
      includes the IL-4R alpha chain but not the gamma c chain. Another mutant protein,
      IL-4(R88D), which has greatly reduced affinity for IL-4R alpha, was found to
      inhibit responses by normal B cells to IL-4 but not to IL-13. IL-4(R88D), did
      not, however, inhibit X-SCID B cell responses to IL-4. This result is consistent
      with IL-4(R88D) inhibition of responses mediated by receptor complexes that
      include the gamma c chain. We propose that X-SCID B cells responses to IL-4 are
      mediated by an IL-13 receptor complex comprised of the IL-4R alpha chain
      associated with the recently cloned IL-13R binding protein. This model has major
      implications for understanding normal B cell responses to IL-4.

PMID- 9022006
TI  - Regulated production of the interferon-gamma-inducible protein-10 (IP-10)
      chemokine by human neutrophils.
AB  - Interferon-gamma (IFN-gamma)-inducible protein-10 (IP-10), a member of the C-X-C
      sub-family of chemokines, is known to be produced by monocytes, lymphocytes,
      keratinocytes and endothelial cells in response to IFN-gamma. Here, we show that
      human polymorphonuclear neutrophils (PMN) also have the ability to produce IP-10.
      IFN-gamma alone had a modest effect on IP-10 mRNA accumulation, whereas tumor
      necrosis factor-alpha (TNF-alpha), yeast particles opsonized with IgG (Y-IgG),
      lipopolysaccharide (LPS), and formyl-methionyl-leucyl-phenylalanine (fMLP) all
      failed to up-regulate IP-10 gene expression. However, stimulation of neutrophils
      with IFN-gamma in combination with either TNF-alpha or LPS (but not with Y-IgG or
      fMLP) resulted in a considerable induction of IP-10 mRNA transcripts, as well as
      in the extracellular release of the protein. In contrast, the best inducer of IP
      10 release from peripheral blood mononuclear cells was IFN-gamma alone.
      Furthermore, mRNA stabilization analyses demonstrated that IP-10 mRNA isolated
      from PMN stimulated with IFN-gamma only, or with IFN-gamma plus either TNF-alpha
      or LPS, had similar half-lives. Finally, we found that interleukin-10, a known
      inhibitor of chemokine production in PMN, moderately suppressed the extracellular
      production of IP-10 in neutrophils stimulated with IFN-gamma plus either LPS or
      TNF-alpha. Since IP-10 is a potent chemoattractant for activated T lymphocytes,
      the ability of neutrophils to produce IP-10 might contribute to the evolution and
      progression of the inflammatory response.

PMID- 9022008
TI  - CD21 augments antigen presentation in immune individuals.
AB  - CD21 (complement receptor 2, CR2) binds the C3 degradation products, iC3b and
      C3d, which are covalently linked to antigen or immune complexes in the process of
      complement activation. The ability of antigen-nonspecific B cells to present
      immune complexes containing high titers of acquired antibodies was tested.
      Influenza virus was incubated with serum from immune donors to create complement
      containing complexes. These bound specifically to CD21 on transfected fibroblasts
      and B cell lines, as measured by microcytofluorimetry. Binding of immune
      complexes was ablated by inactivation of serum complement. In addition, the
      immunoglobulin in immune human serum blocked influenza binding to cells in the
      absence of complement, implying a minimal role for immunoglobulin-Fc receptor
      interactions in this system. Significant immune complex binding required a
      threshold level of CD21 expression, suggesting that only those cells with the
      highest levels of CD21 are likely to participate in the processing of
      macromolecular antigens. B cells pulsed with complement-influenza complexes
      elicited an augmented response from a panel of influenza-specific, class II
      restricted T cell clones, as compared with those which had bound immunoglobulin
      influenza complexes lacking complement. This enhanced response did not require
      CD35. In addition, B cell lines expressing higher levels of CD21 were more
      efficient in processing antigen than those with lower levels. These findings
      suggest that presentation of antigen by B cells in immune individuals is
      dependent on the binding of complement-antigen immune complexes to CD21.

PMID- 9022009
TI  - Direct and sequential switching from mu to epsilon in patients with Schistosoma
      mansoni infection and atopic dermatitis.
AB  - Immunoglobulin isotype switching to IgE in patients infected with Schistosoma
      mansoni and patients with atopic dermatitis was studied. Patients with parasitic
      infections or allergic diseases have a higher production of IgE. We found a four
      fold increased production of I epsilon RNA in both patient groups as compared to
      control donors. The increased expression of germ-line transcripts correlates with
      higher serum IgE levels. Nested primer polymerase chain reaction was used to
      generate S mu/S epsilon fragments from DNA of patient peripheral blood
      mononuclear cells. Twenty-nine out of fourty sequenced switch fragments had
      undergone direct joining from S mu to S epsilon whereas seven fragments showed
      mono sequential switching from S mu via either S mu, S gamma2, S gamma4 or S
      epsilon to S epsilon and four fragments demonstrated double sequential switch: S
      mu/S mu/S gamma1/S epsilon, S mu/S gamma2/S epsilon/S epsilon or S mu/S gamma1/ S
      gamma2/S epsilon. The sequential switching had occurred either via deletions or
      inversions. Mapping of the breakpoints showed hot spots for recombination within
      S mu, S gamma1 and S epsilon. To our knowledge, this is the first in vivo study
      in humans demonstrating that switching to IgE can occur from sequential
      rearrangements via gamma1, gamma2 or gamma4.

PMID- 9022010
TI  - Thymic stromal organization is regulated by the specificity of T cell
      receptor/major histocompatibility complex interactions.
AB  - The thymic architecture is normally compartmentalized into a central medulla
      surrounded by a peripheral cortical region. We investigated how
      compartmentalization of the thymic stroma is regulated using T cell receptor
      (TCR)-transgenic mouse models. Our studies show that the signals generated by
      TCR/peptide/major histocompatibility complex interactions regulate thymic stromal
      cell compartmentalization. In TCR-transgenic mice, normal stromal cell
      compartmentalization occurs when the transgenic TCR is expressed on a background
      that does not result in skewing toward either positive or negative selection. In
      models representing strong positive selection, the thymic stromal elements do not
      fully organize into a central medulla. Instead, small medullary foci are
      dispersed throughout the thymus with some regions residing directly under the
      capsule. The highest degree of disorganization in medullary epithelial regions is
      observed in TCR-transgenic mice that exhibit negative selection. Although the
      medullary foci lack central organization, the expression in these regions of
      CD80, CD86 and CD40, as well as the clustering of dendritic cells, is similar to
      that observed in medullae of wild-type mice. Thus, the organization of the
      medulla appears to occur in two stages: (1) small medullary epithelial regions
      that are dispersed in fetal thymi expand and associate with antigen-presenting
      cells, and (2) the expanded medullary foci organize into a central medullary
      compartment. Our data suggest a model in which this second stage of stromal cell
      organization is increasingly inhibited as the normal balance of TCR-mediated
      signals is skewed by higher-avidity interactions between thymocytes and antigen
      presenting cells.

PMID- 9022011
TI  - Regulation of interleukin-12 receptor beta1 chain expression and interleukin-12
      binding by human peripheral blood mononuclear cells.
AB  - The interleukin-12 receptor (IL-12R)beta1 chain is an essential component of the
      functional IL-12R on both human T and natural killer cells. In this report it is
      shown that activation of human peripheral blood mononuclear cells (PBMC) with
      anti-CD3 monoclonal antibody (mAb) or phytohemagglutinin resulted in the up
      regulation of IL-12Rbeta1 expression and IL-12 binding. Kinetic studies revealed
      that maximum expression of IL-12Rbeta1 and IL-12 binding occurred on days 3-4.
      Anti-CD3-induced expression of IL-12Rbeta1 chain and IL-12 binding by PBMC was
      augmented by anti-CD28 mAb, indicating that the potentiating effect of anti-CD28
      on T cell responses to IL-12 could be mediated, at least in part, by the
      enhancement of IL-12R expression. Among 16 cytokines tested, IL-2, IL-7 and IL-15
      markedly induced IL-12Rbeta1 expression and IL-12 binding on resting PBMC,
      whereas IL-1alpha and tumor necrosis factor-alpha had a minimal enhancing effect.
      In contrast, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-alpha,
      IFN-gamma, granulocyte/macrophage colony-stimulating factor and transforming
      growth factor (TGF)-beta2 had no detectable enhancing effect. Anti-CD3-induced
      expression of IL-12Rbeta1 and of low-affinity IL-12 binding sites was partially
      inhibited by TGF-beta2, IL-10 and IL-4; however, TGF-beta2 and IL-10 completely
      abolished anti-CD3-induced expression of high-affinity IL-12 binding sites.
      Consistent with the reduction of high affinity IL-12 binding sites, PBMC
      activated with anti-CD3 mAb in the presence of TGF-beta2 or IL-10 failed to
      produce IFN-gamma or to proliferate in response to IL-12. These results suggest
      that Th2 cell-derived cytokines can inhibit IL-12-induced biological functions by
      inhibiting IL-12R expression and that expression of a second subunit of the IL
      12R (IL-12Rbeta2), required for the formation of high-affinity IL-12 binding
      sites, may be more highly regulated by TGF-beta2 and IL-10 than is expression of
      IL-12Rbeta1.

PMID- 9022012
TI  - Blockade of CD28/B7 co-stimulation by mCTLA4-Hgamma1 inhibits antigen-induced
      lung eosinophilia but not Th2 cell development or recruitment in the lung.
AB  - We have studied the role of the CD28/B7 co-stimulatory pathway in the development
      of a Th2-type lung immune response. Mice injected two or three times
      intraperitoneally with ovalbumin in alum adjuvant and then re-exposed to the same
      antigen by intranasal (i.n.) inoculation show infiltration of the lung tissue and
      appearance in the broncho-alveolar lavage (BAL) fluid of significant numbers of
      eosinophils and lymphocytes, in a pattern which is reminiscent of asthmatic
      inflammation. The accumulation of eosinophils in the airways is completely
      dependent on interleukin (IL)-5 secretion by CD4+ T cells. We have used mice
      transgenic for a soluble form of murine CTLA-4 (mCTLA4-Hgamma1) which binds to B7
      molecules on antigen-presenting cells, thereby preventing their interaction with
      T cell-expressed CD28. mCTLA4-Hgamma1-transgenic mice immunized intraperitoneally
      and challenged i.n. with ovalbumin failed to generate any eosinophil
      infiltration, suggesting that little or no IL-5 was secreted in the lungs of
      these mice. In contrast with the complete lack of eosinophils, the numbers and
      phenotypes of infiltrating lymphocytes were comparable in the lungs of mCTLA4
      Hgamma1-transgenic and normal mice. Also, lung lymphocytes from immunized mCTLA4
      Hgamma1-transgenic and normal mice could be shown to secrete comparable amounts
      of IL-4 and IL-5 when stimulated in culture in the absence of mCTLA4-Hgamma1. We
      conclude that mCTLA4-Hgamma1 can efficiently block the production of IL-5 during
      in vivo responses and inhibit eosinophil recruitment, but that it does not block
      the development of CD4+ T cells into Th2 cells with the potential to secrete IL
      5.

PMID- 9022013
TI  - Pattern of usage and somatic hypermutation in the V(H)5 gene segments of a
      patient with asthma: implications for IgE.
AB  - The V(H)5 family contains two functional genes, V5-51 and V(H)32, and appears to
      be over-represented in IgE antibodies from patients with allergic disease.
      Previous sequence analysis of V(H)5 gene segments in IgE has revealed a
      substantial level of somatic hypermutation, with evidence for hotspots. To assess
      characteristics of V(H)5 gene behavior, V(H)5 gene segments in combination with C
      mu, C gamma, C alpha, and C epsilon have been amplified from blood B lymphocytes
      of a patient with atopic asthma. Sequence analysis revealed strong preferential
      usage of one of the two V(H)5 gene segments (V5-51) by IgM, IgG, and IgA. In
      contrast, IgE used both genes equally. Levels of somatic mutation were higher
      following all isotype switches, particularly to IgA. Mutational hotspots were
      identifiable in all isotypes, leading to several common replacement amino acids.
      The dominant mutational site in IgM was a common hotspot at Ser31. IgG, IgA, and
      IgE-derived sequences had mainly common hotspots, with few distinct sites. The
      results indicate that mutational hotspots are a feature of the V(H)5 gene, are
      identifiable at an early stage of somatic hypermutation, and are not a unique
      feature of IgE. Generation of IgE antibodies appears to involve three processes:
      the preferential use of V(H)5 genes, consistent with superantigen stimulation;
      the accumulation of somatic mutations in common hotspots, some of which are in
      complementarity-determining regions (CDR); and the acquisition of non-hotspot
      mutations in CDR, accounting for approximately 50% of replacement amino acids in
      these sites, and presumably contributing to affinity maturation.

PMID- 9022014
TI  - Human Th1 cells preferentially induce interleukin (IL)-1beta while Th2 cells
      induce IL-1 receptor antagonist production upon cell/cell contact with monocytes.
AB  - The role of human T cells in the induction and regulation, upon cell/cell
      contact, of inflammatory responses by monocytic cells was investigated. The
      production of interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1Ra) by the
      monocytic THP-1 cell line was measured upon contact with either Th1 or Th2 cell
      clones. CD4+ T cell clones specific for purified protein derivative of
      Mycobacterium tuberculosis, predominantly Th1 [high interferon (IFN)-gamma and
      low IL-4 producers], or tetanus toxoid, predominantly Th2 (low IFN-gamma and high
      IL-4 producers), were generated. Cell membranes from antigen-stimulated, but not
      from resting T cell clones induced dose-dependent cytokine production by THP-1
      cells. Th1 clones induced higher levels of IL-1beta production (484-806 pg/ml)
      than did Th2 clones (21-114 pg/ml). In contrast, Th1 clones induced lower levels
      of IL-IRa (0.9-7.8 ng/ml) than did Th2 clones (7.0-49.6 ng/ml). Similar results
      were obtained when T cell clones were activated by cross-linked CD3 and CD28. IL
      1beta production by THP-1 cells correlated with IFN-gamma production by T cell
      clones but was unaffected by IFN-gamma neutralization. IL-1Ra production by THP-1
      cells correlated with IL-4 production by T cells and was partially inhibited by
      IL-4 neutralization. These data indicate that activated Th1 and Th2 cells express
      different molecules on the cell surface able to induce distinct pro-inflammatory
      (IL-1beta) or anti-inflammatory (IL-1Ra) responses in monocytes. This
      differential induction of molecules with opposite effects on inflammation
      stresses the functional heterogeneity in CD4+ T cells.

PMID- 9022015
TI  - Human leukocyte antigen phenotype imposes complex constraints on the antigen
      specific cytotoxic T lymphocyte repertoire.
AB  - The memory response to the immunodominant Epstein-Barr virus (EBV) epitope
      FLRGRAYGL, which associates with HLA B8, is exceptionally restricted, being
      dominated by cytotoxic T lymphocytes (CTL) with a single, public T cell receptor
      (TCR). CTL clones that express this receptor fortuitously cross-react with the
      alloantigen HLA B44. However, of the two major subtypes of this HLA, B*4402 and
      B*4403, that differ by a single amino acid, only the former is recognized by
      these mature CTL clones. Individuals heterozygous for HLA B8 and B*4402 use
      alternative TCR for the EBV determinant since the dominant TCR is potentially
      self-reactive. We now demonstrate that this clonotype is also essentially absent
      from the repertoire of CTL directed against the viral epitope in seven from seven
      unrelated individuals heterozygous for HLA B8 and B*4403. Thus immune tolerance
      of these CTL recognizing HLA B*4402 is associated with expression of either
      B*4402 or B*4403. This suggests that tolerance in the human T cell compartment
      requires a lower threshold of recognition than for effector function, thus
      providing a buffer zone minimizing the risk of autoimmunity. These data also
      illustrate the potential for non-restricting HLA molecules to bias dramatically
      the T cell repertoire used for specific immune responses. Such influences may be
      the basis of the "protective" effects of certain HLA alleles in susceptibility to
      autoimmune disorders.

PMID- 9022016
TI  - Bacille Calmette Guerin and interleukin-12 down-modulate interleukin-4-producing
      CD4+ NK1+ T lymphocytes.
AB  - Early production of interleukin-12 (IL-12) by macrophages and of IL-4 from CD4+
      NK1+ T cells influence development of the acquired immune response against
      infectious agents, namely differentiation of interferon-gamma-secreting T helper
      1 (Th1) cells against intracellular pathogens and of IL-4-producing Th2 cells
      against helminths. Evidence has been presented for transient convertibility of
      Th1 and Th2 cells in the presence of the polarizing cytokines IL-4 or IL-12,
      respectively. Moreover, it is likely that IL-4 dominates over IL-12, suggesting
      that Th2 cell development is preferred in the presence of both cytokines.
      Mycobacterium bovis Bacille Calmette Guerin (BCG) and IL-12 are potent inducers
      of Th1 responses. Here we show that BCG and IL-12 down-modulate IL-4-producing
      CD4+ NK1+ TCR alpha/beta(intermediate) liver lymphocytes. Our data provide
      further insights into the mechanisms by which BCG and IL-12 may promote
      unrestricted development of Th1 responses in vivo: BCG and IL-12 not only provide
      the positive stimuli for Th1 cell differentiation, but also interfere with
      antagonizing signals.

PMID- 9022017
TI  - A novel peripheral CD4+ CD8+ T cell population: inheritance of CD8alpha
      expression on CD4+ T cells.
AB  - In this study we show the inheritance of a CD4+ CD8+ peripheral Tcell population
      in the H.B15 chicken strain. A large proportion of alphabeta T cells in
      peripheral blood (20-40%), spleen (10-20%) and intestinal epithelium (5-10%)
      coexpress CD4 and CD8alpha, but not CD8beta. CD4+ CD8alpha alpha cells are
      functionally normal T cells, since they proliferate in response to mitogens and
      signals delivered via the alphabeta T cell receptor as well as via the CD28 co
      receptor. These cells induce in vivo a graft versus host-reaction, providing
      further evidence for their function as CD4+ T cells. The CD4+ CD8alpha alpha T
      cell population was found in 75% of the first progeny and in 100% of further
      progenies, demonstrating that coexpression of CD4 and CD8 on peripheral T cells
      is an inherited phenomenon. In addition, cross-breeding data suggest a dominant
      Mendelian form of inheritance. The hereditary expression of CD8alpha on
      peripheral CD4+ T cells in chicken provides a unique model in which to study the
      regulation of CD4 and CD8 expression.

PMID- 9022018
TI  - Identification and analysis of the chicken CD3epsilon gene.
AB  - The chicken T cell receptor CD3epsilon gene was isolated using a degenerate
      polymerase chain reaction. The 1883 bp long cDNA encoded a transmembrane protein
      of 16.9 kDa lacking N-linked glycosylation sites. Comparison of the chicken and
      mammalian CD3epsilon proteins revealed low homology in the extracellular domain
      with clusters of similarities located around the N-terminal cysteine residue and
      proximal to the transmembrane region. The high conservation of the cytoplasmic
      domain included motifs important for signal transduction. The alignment of all
      CD3gamma, CD3delta and CD3epsilon proteins allowed the identification of highly
      conserved residues and motifs. Southern blot analysis indicated the presence of a
      single copy CD3epsilon gene. The expression of the CD3epsilon transcript was
      limited to T cells and natural killer cells. A recessive mutation of the
      CD3epsilon gene in the CB chicken strain enabled the mapping of the epitope
      recognized by the CT3 monoclonal antibody. This analysis of the first non
      mammalian CD3epsilon gene provides novel information about evolutionary conserved
      structural features and its expression in natural killer cells.

PMID- 9022019
TI  - Human naive B cells cultured with EL-4 T cells mimic a germinal center-related B
      cell stage before generating plasma cells. Concordant changes in Bcl-2 protein
      and messenger RNA levels.
AB  - The T cell-dependent B cell response in vivo occurs in organized
      microenvironments. Alternative routes exist in that early plasma cells are
      generated in the T zone while others emerge later from the germinal center (GC)
      reaction. We investigated whether B cell stages resembling those defined in
      vivo/ex vivo might be induced in an in vitro system in which naive human B cells
      are activated by EL-4 T cells and cytokines. Adult peripheral blood- or cord
      blood-derived B cells were found to mimic an early activated stage (CD38(low),
      IgD+, increased CD5+) followed by a centroblastic GC-related stage (CD38(int),
      CD77+, CD95(Fas)+, Bcl-2 protein(low)) before differentiating into
      morphologically typical, CD38(high), Fas- plasma cells of an immature type (Bcl
      2(low), VLA-5-). The GC-related cells and the plasma cells exhibited spontaneous
      apoptosis in medium, the former also undergoing anti-Fas antibody-induced
      apoptosis in medium as well as during CD40L exposure in the EL-4 cultures. These
      Bcl-2(low) cells maintained a high viability in contact with EL-4 cells. Thus,
      some, major B cell stages with typical functional features as described for cells
      in vivo/ex vivo are sequentially generated in this in vitro system and the
      kinetics of the changes can be analyzed in a synchronized cell population. With
      regard to previous apparently conflicting observations on the Bcl-2 mRNA level in
      GC B cells, we performed competitive reverse-transcription polymerase chain
      reaction. Concordant changes in Bcl-2 mRNA and protein levels were found, i.e.
      during Bcl-2 down-regulation in the GC-related B cells in ongoing EL-4 cultures
      or in medium, and during a more modest up-regulation upon contact with fresh EL-4
      cells. Regulation of Bcl-2 protein, therefore, predominantly occurred at the mRNA
      steady-state level.

PMID- 9022020
TI  - gamma delta cells involved in contact sensitivity preferentially rearrange the
      Vgamma3 region and require interleukin-7.
AB  - Ptak and Askenase showed that both alphabeta and gammadelta cells are required
      for transfer of contact sensitivity (CS). This study confirms that day 4 immune
      cells depleted of gammadelta cells fail to transfer CS to trinitrochlorobenzene
      (TNP-Cl) systemically and demonstrates that administration of anti-gammadelta
      monoclonal antibodies (mAb) in vivo abolishes the CS reaction. Moreover,
      gammadelta cells accumulate at the antigen challenge site: these cells have the
      unusual phenotype CD8alpha+, CD8beta-, IL-4 R+ which we suggest is due to their
      state of activation. Following immunization with contact sensitizer on the skin,
      the absolute number of gammadelta cells increases in the regional lymph nodes
      with a peak at 4 days. Of the gammadelta cells, 80 %, both in the lymph nodes of
      TNP-Cl-immune mice and accumulating at the antigen challenge site are Vgamma3+.
      The gammadelta cells expressing Vgamma3, which is characteristic of dendritic
      epithelial T cells (DETC), obtained 4 days after sensitization, proliferate in
      response to interleukin (IL)-7, but only poorly to IL-2 and IL-4. They also
      respond to concanavalin A and immobilized anti-gammadelta mAb, but not to haptens
      or heat-shocked syngeneic spleen cells. Furthermore, injection of mice with mAb
      to IL-7 inhibits accumulation of Vgamma3+ cells both in the lymph nodes after
      skin sensitization and at the antigen-challenge site. Altogether, these results
      strongly support the view that DETC are related to, or the original source of,
      the gammadelta cells found in the lymph node after skin sensitization and at the
      site of challenge, and that IL-7 is implicated in these phenomena.

PMID- 9022021
TI  - Genetic defect in T lymphocyte-specific homing into peripheral lymph nodes.
AB  - Lymphocytes circulating in the bloodstream home into lymph nodes (LN). T cells
      predominate in peripheral LN (PLN) and B cells in spleen or mucosal tissue, e.g.
      Peyer's patches (PP). DDD/1 mice are unique in marked paucity of LN cells,
      especially T cells. T cell frequency in PLN was 20-40% in this strain, compared
      to 60-80% in others. Immunohistochemistry confirmed the low density of T cells in
      the subcortical area but normal colonization of B cells in cortical area in PLN
      of DDD/1. In contrast, the T cell content of peripheral blood and spleen was
      higher in DDD/1 but that in PP was not significantly different compared to other
      strains. It was thus concluded that this abnormality in DDD/1 results from a
      homing defect of T cells into PLN but not from lymphopenia. Genetical analysis
      showed that the defect in T cell-specific homing was regulated by a single
      autosomal recessive gene, tentatively designated plt (paucity of lymph node T
      cells). Reciprocal bone marrow transplantation indicated that the plt phenotype
      may arise from some defect in PLN stroma but not in lymphocytes. An in vivo
      homing assay using fluorescence-labeled lymphocytes demonstrated that the homing
      defect was specific for T cells but not for B cells. A Stamper-Woodruff assay
      revealed that the binding between lymphocytes and PLN high endothelial venules
      was normal and that L-selectin and its ligand, peripheral node vascular addressin
      (PNAd), were expressed and functioned normally in DDD/1. These results taken
      together indicate that the T cell-specific homing into PLN is disturbed at a post
      adhesion stage in DDD/1. The product of the plt locus may play a pivotal role at
      this stage.

PMID- 9022022
TI  - Overexpression of mitogen-activated protein kinase kinase kinase reversed cAMP
      inhibition of NF-kappaB in T cells.
AB  - cAMP inhibits T cell activation by acting as an antagonist for selective kinases
      and transcriptional factors. We have recently demonstrated that cAMP inhibited c
      Jun N-terminal kinase (JNK) but left the mitogen-activated protein (MAP) kinase
      cascade almost unaffected in T lymphocytes. In accordance with recent reports, we
      also observed a selective suppression of nuclear factor NF-kappaB activation by
      cAMP. The possible link between the JNK cascade and NF-kappaB activation was
      demonstrated by the fact that the active form of MAP kinase kinase kinase
      (deltaMEKK), a constitutive activator of JNK, induced NF-kappaB but not AP-1,
      Oct, and NF-AT in T cells. In contrast, the induction of MAP kinase kinase (MEK)
      MAP kinase did not stimulate NF-kappaB activity. The specific activation of NF
      kappaB by a single MEKK-JNK cascade was thus unusual, given that the activation
      of other transcriptional elements in T cells requires at least two signal
      pathways. This was further confirmed by the fact that cAMP inhibition of NF
      kappaB activation was reversed by overexpression of deltaMEKK.

PMID- 9022023
TI  - Major histocompatibility complex recognition by immune receptors: differences
      among T cell receptor versus antibody interactions with the VSV8/H-2Kb complex.
AB  - The surface residues of the VSV8/Kb complex important for recognition by N15 and
      N26 alphabeta T cell receptors (TCR) were mapped by mutational analysis and
      compared to each other and with epitopes of well-characterized Kb specific
      monoclonal antibodies (mAb). Three features of immune receptor recognition
      emerge. First, the footprints of the two TCR on VSV8/Kb are similar with more
      than 80 % overlap between sites. Given that only 8 of 14 surface exposed VSV8/Kb
      residues identified as critical for TCR interaction are in common, the chemical
      basis of the N15 and N26 interactions is nevertheless distinct. Second, the
      cognate peptide is a major focus of TCR recognition: mutation at any of the three
      exposed side chains (at p1, p4 or p6) abrogates interaction of both TCR as
      measured by functional T cell activation. Third, in contrast to TCR, mAb bind to
      discrete segments on the periphery of the alpha1 and/or alpha2 helices without
      orientational restriction. These findings suggest that unlike soluble antibodies,
      surface membrane receptor-ligand interactions on opposing cells (i.e. TCR
      peptide/ MHC, CD8-MHC) limit the orientational freedom of the TCR in the immune
      recognition process.

PMID- 9022024
TI  - The propensity to apoptosis of centrocytes and centroblasts correlates with
      elevated levels of intracellular myc protein.
AB  - In this study, we investigated the c-myc expression by tonsillar germinal center
      (GC) B cells using reverse transcriptase-polymerase chain reaction, flow
      cytometry, Western blot and in situ immunohistochemical methods. The results
      obtained demonstrate elevated levels of c-myc mRNA and of Myc protein in GC B
      cells compared to those of the other resting or activated tonsillar B cells.
      Separation of GC B cells into centroblasts and centrocytes revealed that, while
      differing in their cell cycle status, surface marker expression and morphology,
      the two cell types had the same propensity to apoptosis and elevated Myc protein
      expression, thus reinforcing the notion of a close correlation between these two
      events. Based upon these observations and other considerations it is proposed
      that elevation of Myc proteins confers to GC B cells a particular propensity to
      apoptosis, while the subsequent decision between progression into the cell cycle
      or programmed cell death is dictated by other signals that are delivered in the
      GC and perhaps operate at the level of other proto-oncogenes.

PMID- 9022025
TI  - CD28-mediated induction of proliferation in resting T cells in vitro and in vivo
      without engagement of the T cell receptor: evidence for functionally distinct
      forms of CD28.
AB  - JJ316 and JJ319 are rat CD28-specific monoclonal antibodies (mAb) of the gamma1
      kappa isotype with identical co-stimulatory potency. At a concentration 100-1000
      fold higher than that required for co-stimulation, JJ316, but not JJ319 induces
      massive proliferation of all T cell subsets in vitro without T cell receptor
      (TCR) triggering. "Direct" stimulation by JJ316 is fully blocked by JJ319,
      indicating that it is not due to cross-reactivity of JJ316 with the TCR complex
      or other activating receptors. JJ316 binds much more slowly to primary T cells
      than JJ319, whereas both antibodies bind with similar kinetics to CD28
      transfected L-929 cells, suggesting that JJ316 binding to T cells requires
      redistribution or a conformational change of CD28. In vivo, JJ316 but not JJ319
      induces rapid and transient proliferation of most CD4 T cells and, indirectly, of
      B cells. These data show that TCR engagement is not an absolute prerequisite
      either in vitro or in vivo for the induction of T cell proliferation through CD28
      and suggest that mAb JJ316 is able to stimulate resting T cells directly by
      recruiting CD28 molecules from an inactive to an active form.

PMID- 9022026
TI  - CD73 mediates lymphocyte binding to vascular endothelium in inflamed human skin.
AB  - Inflammatory diseases of the skin are characterized by abundant lymphocytic
      infiltrates at the site of inflammation, which are critical for the perpetuation
      of chronic disease. Lymphocytes gain entry to the site of inflammation by the use
      of adhesion molecules, which recognize their counterparts on vascular endothelial
      cells. CD73 is a lymphocyte differentiation antigen, which has recently been
      shown to mediate lymphocyte binding to cultured endothelial cells. Here, we have
      examined its expression and function in inflammatory situations using
      inflammatory skin diseases as a model. In several idiopathic and allergic
      disorders of the skin, a vast majority of the skin-infiltrating lymphocytes were
      found to express CD73. However, on the circulating lymphocytes of these patients
      the expression of CD73 does not differ from that of healthy individuals. Of the
      peripheral blood lymphocytes (PBL) of patients, 13 % are CD73+; of these, 9 %
      express the cutaneous lymphocyte antigen (CLA), 32 % express CD45RO, and 86 % are
      L-selectin+. Only 1% of PBL express both CLA and CD73. In contrast, most skin
      infiltrating lymphocytes express both molecules, which led us to investigate the
      role of CD73 in the skin-homing behavior of these cells. In the frozen-section
      adhesion assay, when PBL were treated with the anti-CD73 monoclonal antibody 4G4,
      their binding to the vascular endothelium in inflamed skin was inhibited by 70 %.
      Taken together, our results demonstrate that CD73+ lymphocytes preferentially
      accumulate into inflamed skin and, most importantly, that CD73 is involved in
      lymphocyte binding to vessels in inflamed skin. In the future, these findings may
      offer new means to treat inflammatory disorders of the skin.

PMID- 9022027
TI  - Prevention of autoimmune diabetes mellitus in NOD mice by transgenic expression
      of soluble tumor necrosis factor receptor p55.
AB  - The non-obese diabetic (NOD) mouse represents a relevant animal model of
      autoimmunity for insulin-dependent diabetes mellitus. The pathogenic role of
      tumor necrosis factor (TNF) in insulitis and beta cell destruction observed in
      these mice remains controversial, since injections of TNF or of anti-TNF
      antibodies have been reported to exert protection or acceleration of diabetes,
      depending on the timing of administration. In this study, we demonstrate that, in
      contrast to the non-transgenic littermates, NOD mice with permanent
      neutralization of TNF by high blood levels of soluble TNF receptor p55-human
      FcIgG3-fusion molecules resulting from the expression of a transgene are
      protected from spontaneous diabetes. They are also protected from accelerated
      forms of disease caused by transfer of NOD spleen cells or cyclophosphamide
      injections. This protection is associated with a marked decrease in the severity
      and incidence of insulitis and in the expression of the adhesion molecules MAdCAM
      1 and ICAM-1 on the venules of pancreatic islets. These data suggest a central
      role for TNF-alpha in the mediation of insulitis and of the subsequent
      destruction of insulin-secreting beta-cells observed in NOD mice. They may be
      relevant to cell-mediated autoimmune diseases in general, in which treatment with
      soluble TNF receptors might be beneficial.

PMID- 9022028
TI  - A critical role for interleukin-1 receptor accessory protein in interleukin-1
      signaling.
AB  - Interleukin-1 (IL-1) is a central molecule in inflammation and immune responses
      whose pleiotropic activities are mediated by the type I IL-1 receptor (IL-1RI).
      The IL-1RI alone on the cell surface is silent after binding of the ligand. We
      show that the recently identified IL-1RI accessory protein (IL-1RAcP) converts
      the silent into a fully functional IL-1RI complex. Although transfection of IL
      1RAcP into IL-1RAcP-deficient EL4D6/76 cells did not alter the binding kinetics
      or dissociation constants of the 125I-labeled IL-1alpha/IL-1RI complex, a very
      early event, internalization of the activated receptor complex, and a late event,
      IL-1-stimulated IL-2 production, were successfully restored. Therefore,
      recruitment of IL-1RAcP is a critical early step in the signaling cascade
      mediated by the IL-1RI activation complex.

PMID- 9022029
TI  - Accumulation of somatic hypermutation and antigen-driven selection in rapidly
      cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high
      frequency during the primary anti-hapten response in mice.
AB  - Well-developed germinal centers (GC) contain rapidly dividing surface
      immunoglobulin-negative (sIg-) B cells (centroblasts), and most of their progeny
      are sIg+ B cells (centrocytes) in a resting state. It has been predicted that
      somatic hypermutation occurs in centroblasts, whereas antigen-driven selection
      takes place in centrocytes. The present analysis indicates that murine GC B cells
      bearing sIg with specificity for an immunizing antigen are in a rapidly cycling
      state and increase exponentially in number to occupy spleen GC at high frequency
      during the 1st week after primary immunization; however, the number of these
      cells is significantly reduced in the 2nd week of immunization. During that
      period, these proliferating sIg+ GC B cells accumulate somatic hypermutations
      with nucleotide exchanges indicative of affinity maturation. These sIg+ GC B
      cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting
      activity which results in T cell activation in vitro. These observations indicate
      that the sIg+ GC B cells accumulate somatic hypermutations and undergo antigen
      driven selection through proliferation, probably upon activation by T cells. This
      sIg+ GC B cell population may represent cell cycling centrocytes; however, the
      possibility that these may represent centroblasts undergoing re-expression of sIg
      could not be excluded.

PMID- 9022030
TI  - Constitutive macropinocytosis allows TAP-dependent major histocompatibility
      complex class I presentation of exogenous soluble antigen by bone marrow-derived
      dendritic cells.
AB  - Dendritic cells expanded from mouse bone marrow (BMDC) with
      granulocyte/macrophage-colony-stimulating factor have potent T cell-stimulatory
      properties both in vitro and in vivo. This has been well documented for major
      histocompatibility complex (MHC) class II-restricted responses, and more recently
      using peptide-loaded and protein-pulsed DC for CD8 responses following adoptive
      transfer in mice. An unresolved question concerns the capacity of BMDC to present
      exogenous antigen on MHC class I molecules, an unconventional mode of MHC class I
      loading for which there is now considerable evidence, particularly in
      macrophages. Here, we show that BMDC exhibit high levels of macropinocytosis
      driven by constitutive membrane ruffling activity. Up to one-third of actively
      ruffling and macropinocytosing BMDC transferred pinocytosed horseradish
      peroxidase into the cytosol following a 15-min pulse, suggesting that they might
      be capable of presenting exogenous soluble antigen on MHC class I molecules. We
      show that BMDC presented exogenous ovalbumin to a T cell hybridoma more
      effectively, more rapidly, and at lower exogenous antigen concentrations than BM
      macrophages on a cell-for-cell basis. Presentation was TAP dependent, brefeldin A
      sensitive, and blocked by inhibitors of proteasomal processing, demonstrating use
      of the classical MHC class I pathway. Although effective presentation of
      exogenous antigen by BMDC occurred in the absence of agents which stimulate
      macropinocytosis, treatment with phorbol myristate acetate (PMA) enhanced both
      pinocytosis and MHC class I presentation by BMDC. Finally, PMA-stimulated BMDC
      exposed to exogenous ovalbumin in vitro were able to prime an antigen-specific
      cytotoxic T lymphocyte response following adoptive transfer in vivo.

PMID- 9022031
TI  - Redox regulation of apoptosis: impact of thiol oxidation status on mitochondrial
      function.
AB  - The probability that a cell will undergo apoptosis is in part dictated by the
      cellular redox potential, which is mainly determined by the reduction and
      oxidation of thiol residues on glutathione and proteins. We and others have
      recently shown that mitochondria play a critical role in the apoptotic cascade.
      Here, we address the question as to whether thiol modification regulates
      apoptosis and in which cellular compartment apoptosis-regulatory thiols are
      localized. To resolve this problem, we employed the divalent thiol-reactive agent
      diamide, which causes thiol cross-linking and thus mimics disulfide bridge
      formation, and a panel of monovalent thiol-reactive compounds (which impede
      disulfide bridge formation due to thiol oxidation), one of which is specifically
      targeted to the mitochondrial matrix. Our data indicate that thymocyte apoptosis
      induced by diamide mimics natural apoptosis in the sense that mitochondrial
      transmembrane potential (delta psi(m)) disruption precedes nuclear chromatin
      degradation; that monovalent thiol-reactive compounds inhibit apoptosis induced
      by diamide, glucocorticoids, irradiation, and topoisomerase inhibition; that the
      critical thiols determining cell fate after exposure to diamide, glucocorticoids,
      or DNA damage are likely to be located in the mitochondrial matrix; and that
      thiol oxidation and reduction are critical for apoptosis induction by some
      stimuli (glucocorticoids, DNA damage), but not by Fas/CD95 cross-linking. Taken
      together, these findings suggest that, at least in some pathways of apoptosis,
      mitochondrial thiols constitute a critical sensor of the cellular redox
      potential.

PMID- 9022032
TI  - Alterations in intracellular reactive oxygen species generation and redox
      potential modulate mast cell function.
AB  - The administration of mercuric chloride (HgCl2), gold compounds, or D
      penicillamine to Brown Norway (BN) rats causes a T helper (Th)2 cell-associated
      autoimmune syndrome characterized by the production of a number of
      autoantibodies, marked elevation of serum IgE concentration, and tissue injury in
      the form of a vasculitis and arthritis. We have recently shown that the same
      compounds in vitro sensitize BN rat peritoneal mast cells for IgE-triggered
      mediator release and interleukin-4 mRNA production. We wished to test the
      hypothesis that these agents influence mast cell function via an effect on
      intracellular reactive oxygen species (ROS) production/redox balance. Mast cells
      were obtained from BN rats by peritoneal washout. Incubation with HgCl2, gold
      compounds or D-penicillamine (the latter only in the presence of copper ions) led
      to the intracellular production of ROS as shown by the oxidative production of
      the fluorescent compound 2',7'-dichlorofluorescein. Mast cells were more
      sensitive than splenocytes to this effect. Direct oxidative stress (exposure to
      H2O2) produced a similar sensitization for mediator release to that caused by
      HgCl2. Inhibition of ROS formation by desferrioxamine or catalase diminished the
      enhancement of IgE-mediated serotonin release caused by HgCl2, as did
      replenishment of intracellular glutathione. 2-Mercaptoethanol exacerbated the
      toxicity of HgCl2, perhaps due to the formation of a lipophilic complex that
      enhanced HgCl2 uptake. Blocking of glutathione synthesis increased the toxicity
      of HgCl2, but also abolished any sensitizing effect on mediator release. These
      results support three main predictions of our hypothesis: (1) the compounds known
      to influence mast cell function all lead to the generation of ROS within the mast
      cell; (2) direct oxidative stress causes sensitization for mediator release by
      the mast cell; and (3) modulation of ROS production/redox balance within the mast
      cell modulates the effects of these compounds on mast cell function. The balance
      of oxidative/antioxidative influences may play an important role in the
      modulation of mast cell function, particularly in the context of chemically
      induced autoimmunity.

PMID- 9022033
TI  - Targeted disruption of the V(H) 81X gene: influence on the B cell repertoire.
AB  - We have generated a mutant mouse in which the most D-proximal V(H) gene (V(H)81X)
      has been disrupted by introducing a neomycin-resistance gene into the V(H)81X
      exon by means of gene targeting in embryonic stem cells. The mutant mice
      generated are unable to express the V(H)81X gene but appear to display a normal
      pattern of B cell differentiation as well as normal numbers of bone marrow and
      peripheral B cells from fetal life all through ontogeny. They mount normal immune
      responses to several different antigens tested. In contrast, the distribution of
      V(H) gene rearrangements in the V(H)7183 family is altered in homozygous mutant
      mice. Thus, the antibody repertoire of the targeted mice is modified, at least as
      far as the expression of V(H)7183 genes is concerned.

PMID- 9022034
TI  - Early B cell factor binds to a site critical for lambda5 core enhancer activity.
AB  - The pre-B cell-specific expression of the lambda5 gene is regulated at the level
      of transcription. The 5' region of the lambda5 gene has been shown to contain an
      enhancer that activates heterologous promoters. Here, we show that this enhancer,
      B(lambda5), also acts as a lineage- and tissue-restricted enhancer on its own
      promoter. We define the enhancer core, b(lambda5), that carries around 50% of the
      total enhancer activity. We also demonstrate that the transcription factor early
      B cell factor (EBF) binds to a DNA motif in the lambda5 core enhancer which is
      crucial for enhancer activity, suggesting that lambda5 is a second target gene of
      EBF.

PMID- 9022035
TI  - Direct interaction of Syk and Lyn protein tyrosine kinases in rat basophilic
      leukemia cells activated via type I Fc epsilon receptors.
AB  - Activation of rat mast cells through the receptor with high affinity for IgE (Fc
      epsilonRI) requires a complex set of interactions involving transmembrane
      subunits of the Fc epsilonRI and two classes of nonreceptor protein tyrosine
      kinase (PTK). the Src family PTK p53/p56(lyn) (Lyn) and the Syk/ZAP-family PTK
      p72(syk) (Syk). Early activation events involve increased activity of Lyn and Syk
      kinases and their translocation into membrane domains containing aggregated Fc
      epsilonRI, but the molecular mechanisms responsible for these changes have
      remained largely unclear. To determine the role of Fc epsilonRI subunits in this
      process, we have analyzed Syk- and Lyn-associated proteins in activated rat
      basophilic leukemia (RBL) cells and their variants deficient in the expression of
      Fc epsilonRI beta or gamma subunits. Sepharose 4B gel chromatography of
      postnuclear supernatants from Nonidet-P40-solubilized antigen (Ag)- or
      pervanadate-activated RBL cells revealed extensive changes in the size of
      complexes formed by Lyn and Syk kinases and other cellular components. A fusion
      protein containing Src homology 2 (SH2) and SH3 domains of Lyn bound Syk from
      lysates of nonactivated RBL cells; an increased binding was observed when lysates
      from Ag- or pervanadate-activated cells were used. A similar amount of Syk was
      bound when lysates from pervanadate-activated variant cells deficient in the
      expression of Fc epsilonRI beta or gamma subunits were used, suggesting that Fc
      epsilonRI does not function as the only intermediate in the formation of the Syk
      Lyn complexes. Further experiments have indicated that Syk-Lyn interactions occur
      in Ag-activated RBL cells under in vivo conditions and that these interactions
      could involve direct binding of the Lyn SH2 domain with phosphorylated tyrosine
      of Syk. The physical association of Lyn and Syk during mast-like cell activation
      supports the recently proposed functional cooperation of these two tyrosine
      kinases in Fc epsilonRI signaling.

PMID- 9022036
TI  - Cytotoxic T lymphocytes express a beta3 integrin which can induce the
      phosphorylation of focal adhesion kinase and the related PYK-2.
AB  - Fibronectin has been shown to stimulate tyrosine phosphorylation of a number of
      proteins in the 115-125 kDa range and facilitate degranulation by alloantigen
      specific cytotoxic T lymphocyte (CTL) clones in response to substimulatory
      amounts of anti-CD3 or anti-T cell receptor (TCR). The current study was
      initiated to further characterize integrin expression and usage by these CTL
      clones. We demonstrate that vitronectin and fibrinogen, but not laminin or
      collagen, are also able to both facilitate degranulation in the presence of
      substimulatory anti-CD3 and stimulate tyrosine phosphorylation of these 115-125
      kDa proteins, with a 115-kDa protein being the most prominently phosphorylated.
      These results implicate the expression and usage of the vitronectin receptor,
      alpha beta3 integrin, by these CTL clones. We demonstrate by both flow cytometry
      and immunoprecipitation that CTL clones do in fact express beta3 integrin.
      Immobilized antibody to beta3 stimulates the phosphorylation of the 115-125-kDa
      proteins, suggesting that engagement of beta3 transmits the same signal into
      these cells as fibronectin or vitronectin. The fibronectin and vitronectin
      induced phosphorylation as well as adhesion to either fibronectin or vitronectin
      can be significantly inhibited with antibodies to beta3 integrins. Finally, we
      are able to immunoprecipitate 115-kDa proteins with antiserum to focal adhesion
      kinase and a related kinase, called PYK-2, that becomes phosphorylated in
      response to vitronectin or immobilized anti-beta3. Taken together, these results
      demonstrate that CTL express and use beta3-integrins as signaling molecules which
      can augment TCR-mediated stimulation.

PMID- 9022037
TI  - The proteasome-specific inhibitor lactacystin blocks presentation of cytotoxic T
      lymphocyte epitopes in human and murine cells.
AB  - We describe the effect of the proteasome specific inhibitor lactacystin on the
      metabolic stability of influenza nucleoprotein (NP) and on the generation of
      antigens presented by human and murine class I molecules of the major
      histocompatibility complex to cytotoxic T lymphocytes (CTL). We show that cells
      treated with lactacystin fail to present influenza antigens to influenza-specific
      CTL, but retain the capacity to present defined epitopes expressed as peptides
      intracellularly by recombinant vaccinia viruses. This block in antigen
      presentation can be overcome by expressing the viral protein within the lumen of
      the endoplasmic reticulum, confirming the specificity of lactacystin for
      cytosolic proteases. We also show that the effect of lactacystin on antigen
      presentation correlates with the block of breakdown of a rapidly degraded form of
      the influenza NP linked to ubiquitin. These results demonstrate that proteasome
      dependent degradation plays an important role in the cytosolic generation of CTL
      epitopes.

PMID- 9022038
TI  - Lack of F1 anti-parental resistance in H-2b/d F1 hybrids devoid of beta2
      microglobulin.
AB  - F1 hybrid mice often reject parental hematopoietic grafts, a phenomenon known as
      hybrid resistance. Hybrid resistance is mediated by natural killer (NK) cells and
      although the molecular interactions responsible for this phenomenon are largely
      unknown, one hypothesis suggests that parental cells are rejected because they
      fail to express a complete set of host major histocompatibility complex (MHC)
      class I molecules. Inherent in this theory is that NK cells in the F1 hybrid are
      instructed by self MHC class I molecules to form an NK cell repertoire capable of
      reacting against cells lacking these self MHC class I molecules. Here, we show
      that C57BL/6 x DBA/2 mice (H-2b/d) devoid of beta2-microglobulin (beta2m) are
      incapable of rejecting beta2m-/- parental C57BL/6 cells (H-2b) both in vivo and
      in vitro. From this, we conclude that the development of an NK cell repertoire,
      at least in F1 mice of the H-2b/d haplotype, requires expression of MHC class I
      molecules complexed with beta2m.

PMID- 9022039
TI  - Serum amyloid A gene expression level in liver in response to different
      inflammatory agents is dependent upon the nature of activated transcription
      factors.
AB  - Serum amyloid A (SAA) is highly induced during many inflammatory episodes. The
      induction mechanism in response to turpentine and lipopolysaccharide (LPS), two
      major inducers of this gene, was investigated. Here we present evidence that
      although both agents triggered expression, SAA mRNA synthesized in the turpentine
      injected rabbit liver is many-fold higher compared to that found in LPS-injected
      rabbit liver. We demonstrate that differential level of activation of C/EBP and
      NF-kappaB that interact with the proximal promoter of SAA gene is responsible for
      the differential expression. A very high level of C/EBP induction with little or
      no activation of NF-kappaB factors was noted when turpentine was used as the
      inducer. LPS, on the other hand, activated NF-kappaB and C/EBP, which were
      detected only at the early phase of induction process. These results indicate
      that different pathways might be activated for the regulation of hepatic
      expression of SAA by different inflammatory agents. One of the pathways,
      triggered by LPS, requires participation of both NF-kappaB and C/EBP. A second
      pathway, triggered by turpentine, involves only C/EBP family of transcription
      factors.

PMID- 9022040
TI  - The murine L-plastin gene promoter: identification and comparison with the human
      L-plastin gene promoter.
AB  - Plastins (or fimbrins) are a family of actin-binding proteins that are conserved
      from yeast to humans. In mammals, three tissue-specific plastin isoforms have
      been identified. The L isoform (L-plastin) is normally expressed only in
      leukocytes but is also found in >90% of neoplastic nonleukocyte human cells.
      Because L-plastin expression in tissue-specifically regulated in both humans and
      rodents, it is likely that similar mechanisms regulate L-plastin gene expression
      in human and rodent cells and that they could be identified by comparing the
      function and nucleotide sequences of the human and murine L-plastin gene
      promoters. Previously, we reported the isolation and characterization of the
      human L-plastin gene promoter. In this study, we isolated a murine L-plastin 5'
      end cDNA and used it as a probe to isolate several murine genomic clones. A
      representative clone contained 7 kb of the flanking region, 0.1 kb of the first
      exon, and 9.9 kb of the first intron. A continuous 1,354-bp sequence was
      identified around the first exon. Five transcription initiation sites were found
      40 to 73 bp downstream from a perfect TATA box. Alignment of the sequence with
      its human counterpart revealed approximately 60% homology in a 1-kb region
      spanning the first exon and the flanking region. The TATA box, one ER binding
      site, and two ETS binding sites were completely conserved. An Sp1 binding
      sequence in the human promoter was partially conserved in the murine promoter but
      could still bind to Sp1. A second ER binding sequence, lying 5' adjacent to the
      TATA box in the human promoter, was conserved only at the 3' half-site in the
      murine promoter; the 5' half-site was changed into a potential AP1 binding site.
      This AP1/ER hybrid sequence was incapable of binding to ER. However, both human
      and murine promoters were found to function equally well in either human or
      murine leukocytes.

PMID- 9022041
TI  - The inducible lactose operator-repressor system is functional in the whole
      animal.
AB  - Mouse liver cell lines that bear a stably integrated lactose operon repressor
      (lacI) gene and a Ha-ras gene linked to a lactose operator-containing SV40 early
      promoter were generated. When grown in medium containing more than 0.1 mM
      isopropyl beta-D-thiogalactoside (IPTG), the Ha-ras gene was induced up to 20
      fold. Maximum induction of Ha-ras gene expression occurred after 12 h of
      exposure. The tumorigenicity of these cell lines in syngeneic mice was enhanced
      when the mice were maintained on drinking water containing 12.5 mM IPTG. Ha-ras
      gene expression in tumors was strongly induced in the presence of IPTG in vivo.
      Induction of Ha-ras gene expression in mice was consistently observed after 48 hr
      of exposure to drinking water containing IPTG. This system provides an approach
      for studying the function of oncogene in vivo as well as other genes of interest.

PMID- 9022042
TI  - The mouse prosaposin locus: promoter organization.
AB  - Prosaposin is a multifunctional protein that, when secreted, functions as a
      neurotrophic agent and, when retained in the lysosomes, is processed to essential
      glycosphingolipid hydrolase activator proteins. The prosaposin locus is
      temporarily and spatially regulated at the transcriptional and post-translational
      levels. The prosaposin gene has been partially characterized, but the 5' region
      has not. RACE, S1 nuclease protection, and sequence analysis were used to
      characterize the first intron and first exon as well as the 5'-flanking regions
      from murine P1 clones. The first intron is approximately 15 kb in length and the
      complete gene is approximately 25 kb. The transcriptional initiation sites are
      located 87 and 94 bp 5' to the ATG in exon 1. Using luciferase as a reporter gene
      and transfection into NS20Y, NIH-3T3, or SF-7 Sertoli cell cultures, deletion
      constructs from the 5' putative promoter region were shown to contain positive
      and negative regulatory elements within 2,400 bp 5' to the transcription start
      site. A negative regulatory element is located between 742 and 310 bp 5' to the
      transcription start site. These studies provide insight into the regulation of
      this unique "lysosomal" locus.

PMID- 9022043
TI  - Germ cell-somatic cell dichotomy of a low-density lipoprotein receptor gene
      family member in testis.
AB  - Members of the low-density lipoprotein receptor (LDLR) supergene family interact
      with a large number of diverse ligands. One of the relevant receptors is the
      recently characterized LDLR relative with eight ligand-binding repeats, termed
      LR8, which exists in two splice variant forms. The gonads, relying on receptor
      mediated lipoprotein supply for steroidogenesis, and on interplay of germ cells
      with somatic cells, provide a particularly attractive setting to study details of
      the expression of LR8. Here we show by polymerase chain reactions and Northern
      analysis, as well as by in situ hybridization, that the longer of the two splice
      variants (LR8+), containing an additional region defining an O-linked sugar
      domain, is produced in the somatic cells of chicken testis, whereas the shorter
      form lacking this domain (LR8-) is expressed in the male germ cells.
      Interestingly, as shown by transcript analysis and at the functional level by
      ligand blotting, LR8- expression in the spermatoids increases with germ cell
      maturation, but is absent from ejaculated sperm. This constitutes a scenario
      reminiscent of the situation in growing vitellogenic oocytes, which express very
      high levels of LR8-, but lack the receptor following ovulation. Thus, the cell
      specific expression of different LR8 splice variants may relate to the
      requirements of extensive communication and cooperation between germ cells and
      somatic cells in the gonads.

PMID- 9022044
TI  - Involvement of an octamer-like sequence within a crucial region of the androgen
      dependent Slp enhancer.
AB  - Androgen dependence of the mouse sex-limited protein (Slp) gene is conferred by
      an enhancer encompassing a consensus hormone response element (HRE) and sites for
      several nonreceptor factors. The footprint IV (FPIV) region of the enhancer plays
      a key role in hormone- and tissue-specific response, both in vitro and in vivo.
      We characterized FPIV-binding factors by methylation interference analysis and UV
      cross-linking of several complexes evident in gel mobility-shift assays. The
      footprinting analysis revealed that distinct base contacts within the multiple
      nuclear protein-DNA complexes occurred primarily within a sequence similar to an
      octamer transcription factor (Oct-1) binding site. With additional data on
      approximate molecular weights from UV cross-linking, several plausible candidates
      were tested for their DNA binding and functional activity at FPIV. Oct-like
      protein binding in gel-shift assays with several cell and tissue extracts was
      evident using specific competitors and antibodies, but was lower in affinity for
      FPIV than for an Oct-1 consensus site. Site-directed mutation of the FPIV
      sequence to a consensus Oct-1 element within the Slp enhancer context increased
      Oct-1 binding in vitro, but greatly reduced hormonal induction in vivo. This
      suggested that Oct-1 is not directly involved in response, or alternatively, that
      Oct-1 bound to the lower-affinity site interacts with neighboring factors
      significantly differently than Oct-1 bound to a consensus sequence. A sequence
      overlapping the Oct-like element that was similar to a hepatic nuclear factor-4
      (HNF-4) site showed no ability to bind HNF-4 in vitro, nor the related orphan
      receptor, chicken ovalbumin upstream promoter factor (COUP-TF). Intriguingly,
      however, expression of COUP-TF in transfection had a dramatic inhibitory effect
      on response of the androgen-specific enhancer (C' delta9), but did not affect
      other enhancer configurations that can also be induced by glucocorticoid (C
      'delta2). This underscores that, despite extensive sequence identity of C' delta9
      and C' delta2, components of the androgen-specific transcription complex differ
      significantly from that of one that is more generally steroid responsive.

PMID- 9022045
TI  - The transcriptional and translational control of diazepam binding inhibitor
      expression in rat male germ-line cells.
AB  - The diazepam binding inhibitor [DBI, also known as acyl-CoA-binding protein,
      (ACBP), or endozepine] is a 10-kD protein that has been suggested to be involved
      in the regulation of several biological processes such as acyl-CoA metabolism,
      steroidogenesis, insulin secretion, and gamma-aminobutyric acid type A
      (GABA(A))/benzodiazepine receptor modulation. DBI has been cloned from
      vertebrates, insects, plants, and yeasts. In mammals, DBI is expressed in almost
      all the tissues studied. Nevertheless, DBI expression is restricted to specific
      cell types. Here we have studied DBI gene expression in the germ-line cells of
      rat testis. The DBI gene was intensively transcribed in postmeiotic round
      spermatids from stages VI to VIII of the seminiferous epithelial cycle. A
      prominent, spermatid-specific upstream transcription initiation site was
      identified in addition to the multiple common transcriptional initiation sites
      found in the somatic tissues. However, no DBI protein was detected in round
      spermatids, suggesting that the DBI transcripts were translationally arrested.
      The DBI protein was detected in the late spermatogenic stages starting from
      elongating spermatids from step 18 (stage VI) onward. The DBI protein was also
      detected in mature spermatozoa and in ejaculated human sperms. The majority of
      DBI was located at the middle piece of the spermatozoons tail enriched with
      mitochondria. On the basis of this observation and the well-established role of
      DBI in acyl-CoA metabolism, we propose that DBI expression in spermatozoa
      reflects the usage of fatty acids as a primary energy source by spermatozoa. The
      biological function of DBI in spermatozoa could thus be related to the motility
      function of sperm.

PMID- 9022046
TI  - Human uteroglobin gene: structure, subchromosomal localization, and polymorphism.
AB  - Human uteroglobin (hUG) or Clara cell 10-kD protein (cc10 kDa) is a steroid
      dependent, immunomodulatory, cytokine-like protein. It is secreted by mucosal
      epithelial cells of all vertebrates studied. The cDNA encoding hUG and the 5'
      promoter region of the gene have been characterized previously. Here, we report
      that the structure of the entire hUG gene is virtually identical to those of
      rabbit, rat, and mouse. It is localized on human chromosome 11q12.3-13.1, a
      region in which several important candidate disease genes have been mapped by
      linkage analyses. Our data indicate that candidate genes for atopic (allergic)
      asthma and Best's vitelliform macular dystrophy are in closest proximity to the
      hUG gene. To determine whether hUG gene mutation may be involved in the
      pathogenesis of these diseases, we studied two isolated groups of patients, each
      afflicted with either atopy or Best's disease, respectively. We detected a single
      base-pair change in the hUG gene in Best's disease patients and normal controls
      but no such change was detected in atopy patients. This alteration in hUG gene
      sequence in Best disease family appears to be a polymorphism. Although the
      results of our investigation did not uncover mutations in hUG gene that could be
      causally related to the pathogenesis of either of these diseases, its
      conservation throughout vertebrate phyla implies that this gene is of
      physiological importance. Moreover, the close proximity of this gene to several
      candidate disease genes makes it an important chromosomal marker in cloning and
      characterization of those genes.

PMID- 9022047
TI  - Genomic structure and promoter region of the murine Janus-family tyrosine kinase,
      Jak3.
AB  - Genomic DNA sequences encoding the murine Janus family tyrosine kinase Jak3 were
      isolated to determine the intron-exon structure of the gene and to investigate
      the phylogeny of Jak-family kinases. The murine Jak3 gene comprises approximately
      15 kbp of genomic DNA and consists of 23 exons. The organization of sequences
      encoding the pseudo-kinase domain of Jak3 is similar to the intron-exon structure
      encoding catalytic domains of Src-family tyrosine kinases, whereas the pattern of
      introns-exons encoding the Jak3 kinase domain shows no structural similarity to
      that of other tyrosine kinase genes. Genomic analysis further indicates that
      alternative splicing gives rise to different forms of the murine Jak3 mRNA
      encoding different isoforms of the Jak3 protein. Analysis of Jak3 intron-exon
      structure also suggests that a mutation in the human JAK3 gene responsible for a
      severe combined immune deficiency (SCID) phenotype results from aberrant splicing
      of the JAK3 transcript. Finally, potential regulatory sequences in the upstream
      region of the murine Jak3 gene were analyzed and are discussed in relation to the
      known expression pattern of Jak3.

PMID- 9022048
TI  - Expression and alternative processing of a chicken gene encoding both growth
      hormone-releasing hormone and pituitary adenylate cyclase-activating polypeptide.
AB  - The chicken growth hormone-releasing hormone (GRF) gene was isolated, sequenced,
      and characterized. In addition, three different mRNAs were isolated from juvenile
      and adult brain. The first cDNA encoded for a GRF(1-46), the second cDNA encoded
      for a GRF(1-43) due to a sliding intron boundary, and the third skipped exon four
      and encoded only GRF(33-46). We also determined that juvenile chicken mRNA
      encoding GRF is expressed in the brain and gonads, but not in the pituitary,
      heart, liver, kidney, crop, small intestine, large intestine, eye, and muscle.
      This gene is also interesting in terms of evolution because another neuropeptide,
      pituitary adenylate cyclase-activating polypeptide (PACAP), is encoded within the
      same gene (grf/pacap) in chicken, but on a separate gene (pacap) in mammals. We
      showed previously that these two neuropeptides were encoded in the same cDNA in
      fish, but the present evidence in chicken suggests a gene duplication in stem
      mammals.

PMID- 9022049
TI  - A novel technique for the study of Ras activity: electroporation of [alpha
      32P]GTP.
AB  - An efficient, simple, and reproducible procedure for the assessment of Ras
      activity present in adherent mammalian cells is described. [alpha-32P]GTP was
      introduced by in situ electroporation into mouse C3H10T1/2 fibroblasts or their
      ras(val12)-transformed derivatives. After a 3-hr incubation at 37 degrees C, Ras
      was immunoprecipitated from cell extracts and the Ras-bound GTP/GTP + GDP ratio
      was determined by thin-layer chromatography. Contrary to Streptolysin-O
      permeabilization, the cells are not affected in any detectable way by the
      procedure, so that [alpha-32P]GTP binding and conversion to [alpha-32P]GDP can be
      studied over a period of time for the measurement of steady-state Ras activity.
      The results show that careful control of electric field intensity results in a
      great increase in the efficiency and specificity of labelling compared to the
      addition of [32P]orthophosphate to the culture medium, while the GTP/GTP + GDP
      ratios obtained were essentially the same as after in vivo labeling.

PMID- 9022050
TI  - Endocytosis of the rat somatostatin receptors: subtype discrimination, ligand
      specificity, and delineation of carboxy-terminal positive and negative sequence
      motifs.
AB  - Endocytosis of the five rat somatostatin receptor subtypes (SSTR1-5) was
      investigated in transfected HEK cells by biochemical ligand binding assays and
      confocal microscopic analysis. Phenylarsine oxide-sensitive internalization of
      SSTR1-3 is dependent on SST-14 or SST-28, whereas only the octacosapeptide
      triggers this reaction with SSTR5. SSTR4 is not internalized with either SST.
      Internalized SSTR3 is cycled back to the plasma membrane while endocytosed rho
      Ala1-SST-14 remains inside the cell. Delineation of sequence motifs responsible
      for internalization of SSTR3 revealed multiple serines and a threonine (Ser-341,
      Ser-346, Ser-351, and Thr-357) within the carboxy-terminal tail of which Ser-351
      and Thr-357 were the most effective ones. Chimeras in which various segments of
      the carboxyl terminus of SSTR4 were replaced by the corresponding regions of
      SSTR3 were internalized as long as they contain the Ser/Thr motif. However, this
      internalization reaction was suppressed when the chimeras were extended by the
      carboxyl terminus of SSTR4 (residues 320-384), suggesting the presence of a
      negative control element in that region. Step-wise truncation of the carboxyl
      terminus of wild-type SSTR4 revealed a motif of three amino acid residues Glu-Thr
      Thr (SSTR4-330-332) that is responsible for preventing internalization and may be
      important in regulating endocytosis of this receptor subtype.

PMID- 9022051
TI  - Reactivation and graded axial expression pattern of Wnt-10a gene during early
      regeneration stages of adult tail in amphibian urodele Pleurodeles waltl.
AB  - Adult urodele amphibians such as Pleurodeles waltl are able to regenerate their
      amputated limbs or tail. The mechanisms implicated in growth control and
      formation of the blastema are unknown but it has been proposed that regeneration
      in newts may proceed through reactivation of genes involved in embryonic
      development. Knowing the role of Wnt genes in the patterning of the primary and
      secondary axes of the vertebrate embryo, we suspected that some of these genes
      could be involved in axial pattern during newt tail regeneration. Pwnt-10a gene,
      cloned from a newt tail regenerate cDNA library, showed an expression pattern
      compatible with such a role in tail regenerates. Pwnt-10a, which is highly
      expressed during embryonic development (from gastrula to tailbud-stage) and
      weakly expressed in the adult tail, is strongly re-expressed during tail
      regeneration. In the blastemal mesenchyme Pwnt-10a transcripts exhibited a graded
      distribution along the antero-posterior axis, the mRNA accumulation being maximal
      in the caudal most part corresponding to the growing zone. These findings
      strongly support the view that Pwnt-10a may act in cooperation with other factors
      to control growth and patterning in newt tail regeneration. Until now Wnt-10a was
      only known to be involved in central nervous system development; our results
      suggest that this gene may also play a role in other developmental processes.

PMID- 9022052
TI  - Epidermal growth factor system is a physiological regulator of development of the
      mouse fetal submandibular gland and regulates expression of the alpha6-integrin
      subunit.
AB  - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha)
      regulate branching morphogenesis of fetal mouse submandibular gland (SMG)
      rudiments in vitro. The EGF system (EGF, TGF-alpha, and their shared receptor,
      EGFR) also regulates expression of integrins and their ligands in the
      extracellular matrix. We show here that inhibition of EGFR tyrosine-kinase
      activity by a tyrphostin retards in vitro development of SMGs. Using total RNA
      isolated from pooled SMGs taken from intact mouse fetuses, mRNA transcripts for
      EGF, TGF-alpha, and EGFR were detected by reverse transcription-polymerase chain
      reaction (RT-PCR), and age-dependent variations in the levels of these mRNA were
      quantitatively determined by nuclease protection assays. These findings suggest
      that the EGF system is operative in the in vivo development of this gland. alpha6
      Integrin subunit was localized by immunofluorescence at the basal surface of
      epithelial cells. Branching morphogenesis of cultured SMG rudiments was inhibited
      by anti-alpha6 antibodies. Synthesis of alpha6-subunit in cultured SMGs, detected
      by metabolic labeling and immunoprecipitation, was increased by EGF and
      drastically reduced by tyrphostin. RT-PCR revealed that mRNAs for alpha6- and
      beta1- and beta4-integrin subunits are expressed at all ages between embryonic
      day 13 and postnatal day 7. These findings suggest that 1) the EGF system is a
      physiologic regulator of development of fetal mouse SMG, and 2) one mechanism by
      which it acts may be by regulating expression of integrins, which in turn control
      interaction of epithelial cells with the extracellular matrix.

PMID- 9022053
TI  - Inhibition of eFGF expression in Xenopus embryos by antisense mRNA.
AB  - We studied the effects in Xenopus embryos of overexpression of antisense RNA
      complementary to the messenger RNA of eFGF. We show that the expression of sense
      RNA can be severely depressed in the presence of an excess of antisense RNA. This
      occurs by both partial destruction of the message and by a depression of
      translation of the residual message. The diminution of inducing activity of eFGF,
      measured in animal cap assays either by activation of the Brachyury gene or by
      morphology, parallels the reduction of translation. Endogenous eFGF expression is
      reduced to a similar extent, again by a combination of mRNA destruction and
      inhibition of translation. This shows that the overexpression of antisense RNA
      is, contrary to general opinion, a potentially useful technique for studying gene
      function in Xenopus embryos. However, in the case of eFGF, there is little or no
      overall phenotypic effect on whole embryos. This is probably because of the
      presence of several other FGFs with overlapping expression domains in the early
      embryo.

PMID- 9022054
TI  - Skeletal development in transgenic mice expressing a mutation at Gly574Ser of
      type II collagen.
AB  - Skeletal development of transgenic mice with a type II collagen mutation was
      analyzed and compared with wild-type littermates. The single base substitution in
      Col2a1 resulted in a glycine to serine mutation within the helical domain and
      corresponded to one previously identified in a patient with the lethal human
      chondrodysplasia, hypochondrogenesis (Horton et al. [1992] Proc. Natl. Acad. Sci.
      U.S.A. 89:4583-4587). Skeletal staining of embryos from 14.5 through 18.5 days of
      gestation demonstrated a dwarf phenotype in the transgenic embryos, most notably
      short limb bones and vertebral column that was first detected at 15.5 days post
      coitus. In addition to the reduced length, the extent of ossification was less in
      the transgenic mice. The architecture of the long bone growth plate was abnormal
      in the transgenic tissue, in particular there was no discernible proliferative
      zone. There were few stacks of characteristically flattened cells and the overall
      length of the growth plate in the mutant embryos was reduced. At the
      ultrastructural level, there were fewer collagen fibrils present in the
      transgenic mouse cartilage compared to that of wild-type littermates.
      Ultrastructural localization of collagen types II, IX and XI revealed a similar
      pattern between the transgenic and wild-type pups, suggesting that the collagen
      fibrils present in the matrix of littermates with both phenotypes had a similar
      composition. Skeletal analysis and cartilage histochemistry indicated that effect
      of the type II collagen mutation was to reduce the density of the collagen
      fibrils within the cartilage matrix which was associated with delayed bone
      formation and resulted in a short-limbed phenotype.

PMID- 9022055
TI  - Restricted expression of cadherin-8 in segmental and functional subdivisions of
      the embryonic mouse brain.
AB  - We have cloned full-length cDNA of a novel mouse cadherin ("mCad8"). The deduced
      amino acid sequence of the mature form of mCad8 shows 98.2% identity with the
      sequence of human cadherin-8. The expression of mCad8 was studied by in situ
      hybridization in mouse embryos of 9.5-14 days gestation (E9.5-E14). Results show
      that mCad8 expression is restricted to particular subdivisions of the early
      central nervous system (CNS) and to the thymus. In the CNS, mCad8 expression was
      observed from E11.5. In the telencephalon, mCad8 is expressed by the ventricular
      layer of the ganglionic eminence, by cortical areas, and by cells at the caudato
      pallial angle. In the diencephalon, the margins of one mCad8-positive area
      correspond to the borders of the ventral thalamic neuromere, as confirmed by
      mapping the expression of gene regulatory proteins (Dlx-2, Pax-6, and Gbx-2). In
      the rhombencephalon, two large groups of mCad8-expressing cells were seen in the
      pons and in an area of the lateral basal plate of the myelencephalon. These
      groups of cells extend from the intermediate zone to the mantle zone at E12.5 and
      later form the anlage of the pontine and the facial nuclei. In conclusion, the
      expression of mCad8 reflects, in part, the neuromeric organization of the early
      embryonic CNS. In the mantle layer, mCad8 is expressed by developing gray matter
      structures, such as brain nuclei, suggesting a role for mCad8 in brain
      morphogenesis.

PMID- 9022056
TI  - STAT signaling is active during early mammalian development.
AB  - Cytokine activation of gene expression can be mediated through signal transducer
      and activator of transcription (STAT) signaling pathways resulting in expression
      of target genes. Because many cytokines have important regulatory roles during
      early development, we wanted to ascertain whether STAT signaling was also active
      at this time and could therefore have important roles in mediating developmental
      processes. We have found that Stat1 and Stat3 mRNAs are present in both maternal
      and extraembryonic tissues during early postimplantation stages of murine
      development. Furthermore, analyses of STAT activity in E4.5-E9.5 decidual
      swellings by electrophoretic mobility shift assay demonstrated that Stat3 protein
      was active during this early developmental period. The identification of
      activated Stat3 demonstrates that STAT signaling functions during early
      postimplantation development in the mouse are likely to be important during early
      embryogenesis.

PMID- 9022057
TI  - Differential expression of transcripts encoding retinoid binding proteins and
      retinoic acid receptors during placentation of the mouse.
AB  - We report the distribution of transcripts from genes encoding the retinol binding
      protein (RBP), the cellular retinol binding proteins (CRBP I, II) and retinoic
      acid binding proteins (CRABP I, II), the retinaldehyde dehydrogenase type 2
      (RALDH-2), the retinoic acid receptors (RARs), and the retinoid X receptors
      (RXRs) in mouse placental tissues from 6.5 to 19.5 days postcoitum (dpc). During
      early placentation, RBP and RALDH-2 gene expression are restricted to the
      endoderm of the visceral yolk sac and the outer uterine epithelium, respectively,
      whereas CRBP I transcripts are detected in the visceral yolk sac and in the
      presumptive chorioallantoic placenta. By 15.5 dpc, CRBP I expression is down
      regulated in the yolk sac where CRBP II becomes strongly expressed. Expression of
      CRBP II is also detected in the trophoblastic giant cells. Throughout
      placentation, the expression patterns of the CRABP I and II genes partly overlap
      in the decidual tissue and the vacuolar zones of the decidua, suggesting a role
      for these binding proteins in sequestering free retinoic acid from maternal
      blood, thus regulating its availability to the embryo. RAR alpha is ubiquitously
      expressed in all placental tissues, except in trophoblastic giant cells, at all
      stages studied. During early placentation, RAR beta and RAR gamma are co
      expressed in the decidua but differentially expressed in the chorionic region
      (RAR beta, 10.5 to 12.5 dpc) and the presumptive labyrinth (RAR gamma, 7.5 to
      12.5 dpc). During the same stages, RXR alpha is strongly expressed in the
      presumptive placenta. RAR gamma remains weakly expressed in the labyrinth until
      15.5 dpc, whereas RXR alpha exhibits a strong expression in this zone until
      birth, suggesting a role for these receptors in the development and function of
      the definitive placenta.

PMID- 9022058
TI  - Isolation and characterization of the platelet-derived growth factor beta
      receptor promoter.
AB  - The PDGFbeta r gene has been implicated in many physiological processes including
      development and wound healing. Aberrant expression of the receptor is seen in
      many pathological conditions such as atherosclerosis and inflammatory diseases.
      To study the mechanisms of PDGFbeta r regulation, we identified the regulatory
      regions of the gene. We have cloned and characterized the promoter region of the
      platelet-derived growth factor beta receptor (PDGFbeta r). We isolated a 4.5 Kb
      genomic fragment which confers PDGFbeta r tissue-specific promoter activity. This
      fragment can direct transcription of a luciferase reporter gene in a cell
      specific manner which correlates well with the known pattern of expression of the
      PDGFbeta r. The specificity of this clone was demonstrated by its high activity
      in NIH 3T3 fibroblasts and lack of activity in N-MUNG epithelial cells, a pattern
      that parallels the expression of the endogenous PDGFbeta r. We have defined a 614
      bp region encompassing the 5' untranslated region of the gene which includes the
      basal promoter region. We generated transgenic mice that carry the
      chloramphenicol acetyltransferase (CAT) reporter gene under the control of the
      4.5 Kb promoter. The expression pattern of the reporter gene was compared to that
      of the endogenous PDGFbeta r gene. The promoter was able to direct reporter gene
      expression with the same temporal and spatial pattern as the endogenous PDGFbeta
      r. The most prominent expression was in condensing mesenchyme of developing blood
      vessels, bone and tissues adjacent to epithelium. We conclude that this clone
      contains the regulatory regions sufficient to direct expression of the PDGFbeta
      r. The further analysis of this promoter will help elucidate the transcriptional
      regulation of expression of the PDGFbeta r, and provide a useful tool for
      directing expression of heterologous genes.

PMID- 9022059
TI  - Fibroblast growth factor receptors and regeneration of the eye lens.
AB  - If the eye lens of the adult newt, Notophthalmus viridescens, is removed, a new
      lens will regenerate and only from the dorsal, not the ventral, iris. The source,
      pigmented epithelial cells, would normally no longer divide, but upon lentectomy
      they do re-enter the cell cycle and form lens. The cause for this capability is
      unknown, but the mitogenic Fibroblast Growth Factors and their receptors may be
      involved. We have demonstrated that FGF receptors are present and operative in
      lens regeneration, since receptor-directed mitotoxins inhibit regeneration;
      heterogeneity and differential density in FGF-binding and receptor localization
      in iris sectors is also present. We propose that the spatial distribution of FGF
      receptors, especially the amphibian homolog of FGFR-3, is important in initiation
      of regeneration of eye lens.

PMID- 9022060
TI  - Induction of Hsp72 and transient nuclear localization of Hsp73 and Hsp72
      correlate with the acquisition and loss of thermotolerance in postimplantation
      rat embryos.
AB  - A number of cell culture studies have indicated that there is a positive
      correlation between the induction and decay of thermotolerance and the kinetics
      of Hsp72 expression. In this study, we have demonstrated that, in gestational day
      10 embryos, induction and decay of thermotolerance occur over an 8 hr period. To
      test the hypothesis that there is a correlation between loss of thermotolerance
      and the decline of Hsp72 or Hsp73 gene products over time, expression levels of
      both Hsp72 and constitutively expressed Hsp73 mRNAs and proteins were examined at
      several time points following exposure to a thermotolerance-inducing exposure of
      42 degrees C. Our results indicated that Hsp72 mRNA was strongly induced 1 hr
      after exposure but no longer detectable by 8 hr. Although our Western blot
      results indicated that Hsp72 protein was present beyond 8 hr after exposure,
      Northern blot analysis showed that Hsp72 mRNA was no longer present 5 hr after
      exposure to 42 degrees C. The latter finding indicates that no new Hsp72 can be
      synthesized at this time point and beyond. Although there was very little or no
      induction of Hsp73, immunohistochemical analysis revealed a dramatic, transient
      shift in intracellular localization of Hsp73 protein, as well as Hsp72. Under non
      stress conditions, Hsp73 was cytoplasmically localized but localization was
      largely nuclear 1 hr after exposure, when thermotolerance was demonstrable. Hsp73
      and Hsp72 proteins were no longer localized in the nucleus by 8 hr, when
      thermotolerance was no longer detectable. Thus, the induction of Hsp72 and the
      transient nuclear localization of both Hsp72 and Hsp73 correlate with the
      kinetics of thermotolerance in the postimplantation rat embryo.

PMID- 9022061
TI  - Expression of the mouse fibronectin gene and fibronectin-lacZ transgenes during
      somitogenesis.
AB  - Fibronectins (FNs) are essential for the proper development of embryonic
      mesenchymal tissues. A lacZ reporter gene has been fused to 4.9 kbp of DNA from
      the rat FN gene 5' flanking region, and this construct has been microinjected
      into fertilized mouse embryos to investigate the cis elements needed for the
      temporal and spatial regulation of FN in vivo. Histochemical staining of embryos
      for beta-galactosidase activity demonstrated that four independent lines shared a
      specific pattern of lacZ expression, reflecting the activity of the fibronectin
      sequences contained within the transgene. Specifically, somites stained
      positively for lacZ, but expression was spatially and temporally non-uniform,
      with higher levels in more caudal somites after a total of ca. 13 somite pairs
      had formed. This rostral-caudal gradient of lacZ expression in somites of embryos
      beyond this stage resembled the distribution of endogenous FN mRNA, as detected
      by whole mount in situ hybridization. The transgene was not expressed in the
      developing heart where endogenous FN mRNA was detected. Unexpectedly, highly
      localized staining was observed within the neural tube beginning at ca. E10-10.5,
      and two of the lines exhibited additional areas of staining due to the individual
      integration sites. Thus, the 4.9 kbp FN fragment appears to recapitulate closely
      the complex pattern of FN expression observed during somitogenesis. A smaller
      fragment of 0.9 kbp also directed lacZ expression in caudal somites at E9.5,
      suggesting that these sequences are sufficient to establish the spatio-temporal
      pattern.

PMID- 9022062
TI  - Metalloproteinases regulate parietal endoderm differentiating and migrating in
      cultured mouse embryos.
AB  - Extracellular matrix (ECM) adhesion and proteolysis play important roles in
      embryonic development. In previous work (Behrendtsen et al. [1992] Development
      114:447-456) we showed that gelatinase B activity is rate-limiting for
      trophoblast-mediated invasion and degradation of ECM in culture. In the present
      study, we show that metalloproteinases (MMPs) have distinct roles in migration
      along ECM as opposed to invasion through ECM. We investigated the role of ECM
      proteolysis in the differentiation and migration of parietal endoderm (PE), the
      first embryonic migratory cell type, adhering to ECM surfaces. Gelatinase B was
      the major MMP of PE; mRNA and protein were detected in PE of 7.5- and 8.5-day
      embryos. Using cultures of inner cell masses (ICMs) isolated from mouse
      blastocysts, we found that inhibitors of metalloproteinases, specifically, tissue
      inhibitor of metalloproteinases (TIMP)-1 and a peptide hydroxamic acid stimulated
      outgrowth and differentiation of PE from ICMs cultured on fibronectin, but
      inhibitors of plasminogen activators did not. TIMP-1 increased the number of PE
      cells and mean distance migrated and increased expression of the PE
      differentiation marker vimentin; the increase in cell number was not at the
      expense of other cell types. The stimulatory effect of TIMP-1 was most marked on
      low concentrations of substrate fibronectin, decreasing as concentrations of
      fibronectin increased. TIMP-1 also stimulated the outgrowth of PE in blastocyst
      cultures and in ICM/trophectoderm co-cultures; in ICM/trophectoderm co-cultures
      TIMP-1 stimulated PE differentiation on higher concentrations of fibronectin than
      was permissive for ICMs cultured alone. These data indicate that
      metalloproteinase inhibitors preserved the migration-inducing status of the ECM.
      We conclude that metalloproteinases have distinct roles in invasive activity
      through ECM barriers and migratory activity along ECM surfaces.

PMID- 9022063
TI  - Expression of murine Lhx5 suggests a role in specifying the forebrain.
AB  - A LIM homeobox gene, Lim5, is known to be expressed in the forebrain of Xenopus
      and zebrafish (Toyama et al. [1995] Dev. Biol. 170:583-593). Results from
      developmental and comparative studies of its mouse ortholog, Lhx5, indicate that
      this gene may play important roles in forebrain development. Lhx5 expression is
      detected in the most anterior portion of the neural tube at the headfold stage,
      overlapping partially with Otx2 expression domain. After neural tube closure,
      Lhx5 is expressed as a transverse stripe, covering most of the diencephalic
      primordium. This expression recedes to restricted areas as Dlx gene expression
      occurs. By midgestation, both genes, Lhx5 and Dlx5, are expressed in the
      diencephalon and ventral telencephalon in an alternating complementary pattern.
      It may be that Dlx inhibits Lhx5, and this may represent a step of early
      regionalization of the forebrain. Lhx5 is also expressed in midbrain, hindbrain,
      and spinal cord, overlapping extensively with Lhx1 starting from day E10.5 of
      gestation. The early, persistent, and dynamic expression of Lhx5 suggests a
      regulatory function in forebrain formation.

PMID- 9022064
TI  - Cellular localisation of transforming growth factor-beta 2 and -beta 3 (TGF
      beta2, TGF-beta3) in damaged and regenerating skeletal muscles.
AB  - Regeneration involves a number of cellular processes: revascularisation, invasion
      by haemopoietic cells, removal of necrotic tissue and finally reformation of the
      tissues. These processes have been extensively studied in vitro and are known to
      be affected by various growth factors. However, it has proven difficult to
      extrapolate the in vitro results to the in vivo situation. This is partially
      because the response of cells to growth factors is dependent on which other
      regulatory factors are present. The locations of various growth factors within
      regenerating skeletal muscles have been studied but information is not available
      for the transforming growth factor-beta2 (TGF-beta2) or TGF-beta3, even though
      the TGF-betas are putative regulators of revascularisation, inflammation and the
      formation of connective tissue and muscle fibres. In this paper, the cellular
      locations of TGF-beta2 and TGF-beta3 in freeze-lesioned skeletal muscle were
      examined using immunohistochemistry. The amounts and locations of the TGF-betas
      varied depending on the stage of degeneration/regeneration. The first isoform of
      TGF-beta to appear within the lesion was TGF-beta2, which accumulated at the
      junctions between the viable and necrotic portions of fibres. The production of
      TGF-beta2 by the damaged fibres occurred immediately prior to the inflammatory
      reaction. However, these two events are probably independent of each other as the
      TGF-beta2-rich necrotic tissue was not preferentially phagocytosed. The
      haemopoietic cells contained TGF-beta3 immunoreactivity and the lesioned area
      became progressively rich in TGF-beta3 as the macrophages accumulated in the
      lesion and removed the TGF-beta2-rich necrotic tissue. In vitro, the TGF-betas
      are potent inhibitors of myogenic fusion and have been postulated to control the
      onset of myotube formation in vivo. Consistent with this idea, the formation of
      myotubes did not occur until the TGF-beta3-positive haemopoietic cells had
      migrated from the ghosts of necrotic fibres. In contrast, fusing satellite cells
      and newly formed myotubes contained strong TGF-beta2 immunoreactivity. This
      observation, coupled with the recent report that satellite cells require
      functional TGF-beta receptors to fuse in vivo, suggests that TGF-beta2 may
      stimulate myotube formation in vivo.

PMID- 9022065
TI  - Insulin and the arginine paradox.

PMID- 9022066
TI  - IFN-gamma, IGIF, and IDDM.

PMID- 9022067
TI  - Cell adhesion and angiogenesis.

PMID- 9022068
TI  - Arthropod- and host-specific gene expression by Borrelia burgdorferi.

PMID- 9022069
TI  - High density lipoproteins, but not other lipoproteins, provide a vehicle for
      sterol transport to bile.
AB  - Unesterified cholesterol (UC) that is taken up by the liver from lipoproteins is
      rapidly mixed by exchange with liver UC. Thus, it is not possible to quantitate
      the transport of UC from different lipoproteins into bile using radiolabeled UC.
      However, plant sterols do not exchange with UC and are secreted in bile with the
      same kinetics as UC. To compare the contribution to bile of sterols from
      different lipoproteins, we perfused isolated rat livers with VLDL, LDL, and HDL
      that were obtained from patients with hereditary phytosterolemia and were rich in
      plant sterols. After 30-min recirculating perfusions, hepatic concentrations of
      plant sterols were not different after different lipoproteins were perfused.
      However, biliary plant sterol secretion was markedly different: with the
      perfusion of either VLDL or LDL there was no increase in plant sterols in bile,
      but with perfusion of HDL, the secretion of plant sterols was increased two- to
      threefold (P = 0.0005). The increase in biliary plant sterols was detected 5-10
      min after HDL was added to perfusates and was similarly large for each of three
      individual plant sterols that was tracked. Results show that when sterol
      transport from lipoproteins into bile can be determined, only HDL provides a
      vehicle for UC elimination in bile that is consistent with its putative function
      in reverse cholesterol transport.

PMID- 9022070
TI  - Diet-induced obese mice develop peripheral, but not central, resistance to
      leptin.
AB  - Leptin administration reduces obesity in leptin-deficient ob/ob mice; its effects
      in obese humans, who have high circulating leptin levels, remain to be
      determined. This longitudinal study was designed to determine whether diet
      induced obesity in mice produces resistance to peripheral and/or central leptin
      treatment. Obesity was induced in two strains of mice by exposure to a 45% fat
      diet. Serum leptin increased in proportion to body weight (P < 0.00001). Whereas
      C57BL/6 mice initially responded to peripherally administered leptin with a
      marked decrease in food intake, leptin resistance developed after 16 d on high
      fat diet; mice on 10% fat diet retained leptin sensitivity. In AKR mice,
      peripheral leptin significantly decreased food intake in both 10 and 45% fat-fed
      mice after 16 d of dietary treatment. However, after 56 d, both groups became
      resistant to peripherally administered leptin. Central administration of leptin
      to peripherally leptin-resistant AKR mice on 45% fat diet resulted in a robust
      response to leptin, with a dose-dependent decrease in food intake (P < 0.00001)
      and body weight (P < 0.0001) after a single intracerebroventricular infusion.
      These data demonstrate that, in a diet-induced obesity model, mice exhibit
      resistance to peripherally administered leptin, while retaining sensitivity to
      centrally administered leptin.

PMID- 9022071
TI  - Leptin accelerates the onset of puberty in normal female mice.
AB  - The fat-derived hormone, leptin, is proposed to serve as an adipostatic signal to
      the brain to reduce food intake and body weight. In addition to its effects on
      body weight, chronic leptin treatment restores puberty and fertility to ob/ob
      mice with total leptin deficiency, and acute treatment substantially corrects
      hypogonadism in mice starved for 2 d without affecting body weight. Leptin may
      therefore be a critical signal, linking adiposity and reproduction. Since body
      weight and adiposity appear to play a critical role in the timing of puberty in
      humans and rodents, and leptin levels rise with increasing adiposity, we studied
      the effects of once daily injections of recombinant leptin on the onset of
      puberty in female mice weaned on day 21 and fed ad libitum. There was a linear
      increase in body weight during the study period, which was not altered by the
      dose of leptin used. Mice injected with leptin had an earlier onset of three
      classic pubertal parameters (i.e., vaginal opening, estrus, and cycling) compared
      with saline-injected controls. Leptin is the first peripheral molecule
      demonstrated to accelerate the maturation of the reproductive axis in normal
      rodents. We propose that leptin is the signal that informs the brain that energy
      stores are sufficient to support the high energy demands of reproduction, and may
      be a major determinant of the timing of puberty.

PMID- 9022072
TI  - CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival.
AB  - Although anatomical barriers and soluble mediators have been implicated in immune
      privilege, it appears that the apoptotic cell death of Fas+ cells by tissue
      associated CD95 ligand (Fas ligand, FasL) is an important component. One clinical
      example of the function of an immune privileged site is the success of human
      corneal transplants, where a very high percentage of transplants accept without
      tissue matching or immunosuppressive therapy. Since the mouse cornea expresses
      abundant Fas ligand and immune privilege has been implicated in the success of
      these transplants, we examined the role of FasL in corneal transplantation. Our
      results show that human corneas express functional FasL capable of killing Fas+
      lymphoid cells in an in vitro culture system. Using a mouse model for corneal
      allograft transplantation, FasL+ orthografts were accepted at a rate of 45%,
      whereas FasL- grafts, or normal grafts transplanted to Fas- mice, were rejected
      100% of the time. Histological analysis found that FasL+ grafts contained
      apoptotic mononuclear cells indicating the induction of apoptosis by the graft,
      while rejecting FasL- corneas contained numerous inflammatory cells without
      associated apoptosis. Taken together our results demonstrate that FasL expression
      on the cornea is a major factor in corneal allograft survival and, thus, we
      provide an explanation for one of the most successful tissue transplants
      performed in humans.

PMID- 9022073
TI  - Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas)
      receptor/ligand system and involves activation of wild-type p53.
AB  - Chemotherapeutic drugs are cytotoxic by induction of apoptosis in drug-sensitive
      cells. We investigated the mechanism of bleomycin-induced cytotoxicity in
      hepatoma cells. At concentrations present in the sera of patients during therapy,
      bleomycin induced transient accumulation of nuclear wild-type (wt) p53 and
      upregulated expression of cell surface CD95 (APO-1/Fas) receptor in hepatoma
      cells carrying wt p53 (HepG2). Bleomycin did not increase CD95 in hepatoma cells
      with mutated p53 (Huh7) or in hepatoma cells which were p53-/- (Hep3B). In
      addition, sensitivity towards CD95-mediated apoptosis was also increased in wt
      p53 positive HepG2 cells. Microinjection of wt p53 cDNA into HepG2 cells had the
      same effect. In contrast, bleomycin did not enhance susceptibility towards CD95
      mediated apoptosis in Huh7 and in Hep3B cells. Furthermore, bleomycin treatment
      of HepG2 cells increased CD95 ligand (CD95L) mRNA expression. Most notably,
      bleomycin-induced apoptosis in HepG2 cells was almost completely inhibited by
      antibodies which interfere with CD95 receptor/ligand interaction. These data
      suggest that apoptosis induced by bleomycin is mediated, at least in part, by p53
      dependent stimulation of the CD95 receptor/ligand system. The same applies to
      other anti-cancer drugs such as cisplatin and methotrexate. These data may have
      major consequences for drug treatment of cancer and the explanation of drug
      sensitivity and resistance.

PMID- 9022074
TI  - Direct glucocorticoid inhibition of insulin secretion. An in vitro study of
      dexamethasone effects in mouse islets.
AB  - The direct effects of glucocorticoids on pancreatic beta cell function were
      studied with normal mouse islets. Dexamethasone inhibited insulin secretion from
      cultured islets in a concentration-dependent manner: maximum of approximately 75%
      at 250 nM and IC50 at approximately 20 nM dexamethasone. This inhibition was of
      slow onset (0, 20, and 40% after 1, 2, and 3 h) and only slowly reversible. It
      was prevented by a blocker of nuclear glucocorticoid receptors, by pertussis
      toxin, by a phorbol ester, and by dibutyryl cAMP, but was unaffected by an
      increase in the fuel content of the culture medium. Dexamethasone treatment did
      not affect islet cAMP levels but slightly reduced inositol phosphate formation.
      After 18 h of culture with or without 1 microM dexamethasone, the islets were
      perifused and stimulated by a rise in the glucose concentration from 3 to 15 mM.
      Both phases of insulin secretion were similarly decreased in dexamethasone
      treated islets as compared with control islets. This inhibition could not be
      ascribed to a lowering of insulin stores (higher in dexamethasone-treated
      islets), to an alteration of glucose metabolism (glucose oxidation and NAD(P)H
      changes were unaffected), or to a lesser rise of cytoplasmic Ca2+ in beta cells
      (only the frequency of the oscillations was modified). Dexamethasone also
      inhibited insulin secretion induced by arginine, tolbutamide, or high K+. In this
      case also the inhibition was observed despite a normal rise of cytoplasmic Ca2+.
      In conclusion, dexamethasone inhibits insulin secretion through a genomic action
      in beta cells that leads to a decrease in the efficacy of cytoplasmic Ca2+ on the
      exocytotic process.

PMID- 9022076
TI  - The vascular effects of L-Arginine in humans. The role of endogenous insulin.
AB  - This study aimed at evaluating whether increased availability of the natural
      precursor of nitric oxide, L-arginine, could influence systemic hemodynamic and
      rheologic parameters in humans and whether the effects of L-arginine are mediated
      by endogenous insulin. 10 healthy young subjects participated in the following
      studies: study I, infusion of L-arginine (1 g/min for 30 min); study II, infusion
      of L-arginine plus octreotide (25 microg as i.v. bolus + 0.5 microg/min) to block
      endogenous insulin and glucagon secretion, plus replacement of basal insulin and
      glucagon; study III, infusion of L-arginine plus octreotide plus basal glucagon
      plus an insulin infusion designed to mimic the insulin response of study I. L
      Arginine infusion significantly reduced systolic (11+/-3, mean+/-SE) and
      diastolic (8+/-2 mmHg, P < 0.001) blood pressure, platelet aggregation (20+/-4%),
      and blood viscosity (1.6+/-0.2 centipois, P < 0.01), and increased leg blood flow
      (97+/-16 ml/min), heart rate, and plasma catecholamine levels (P < 0.01). In
      study II, plasma insulin levels remained suppressed at baseline; in this
      condition, the vascular responses to L-arginine were significantly reduced,
      except for plasma catecholamines which did not change significantly. In study
      III, the plasma insulin response to L-arginine was reestablished; this was
      associated with hemodynamic and rheologic changes following L-arginine not
      significantly different from those recorded in study I. These findings show that
      systemic infusion of L-arginine in healthy subjects induces vasodilation and
      inhibits platelet aggregation and blood viscosity. These effects are mediated, in
      part, by endogenous released insulin.

PMID- 9022075
TI  - Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to
      convert hydroxy-amino acids into glycolaldehyde, 2-hydroxypropanal, and acrolein.
      A mechanism for the generation of highly reactive alpha-hydroxy and alpha,beta
      unsaturated aldehydes by phagocytes at sites of inflammation.
AB  - Reactive aldehydes derived from reducing sugars and lipid peroxidation play a
      critical role in the formation of advanced glycation end (AGE) products and
      oxidative tissue damage. We have recently proposed another mechanism for aldehyde
      generation at sites of inflammation that involves myeloperoxidase, a heme enzyme
      secreted by activated phagocytes. We now demonstrate that human neutrophils
      employ the myeloperoxidase-H202-chloride system to produce alpha-hydroxy and
      alpha,beta-unsaturated aldehydes from hydroxy-amino acids in high yield.
      Identities of the aldehydes were established using mass spectrometry and high
      performance liquid chromatography. Activated neutrophils converted L-serine to
      glycolaldehyde, an alpha-hydroxyaldehyde which mediates protein cross-linking and
      formation of Nepsilon-(carboxymethyl)lysine, an AGE product. L-Threonine was
      similarly oxidized to 2-hydroxypropanal and its dehydration product, acrolein, an
      extremely reactive alpha,beta-unsaturated aldehyde which alkylates proteins and
      nucleic acids. Aldehyde generation required neutrophil activation and a free
      hydroxy-amino acid; it was inhibited by catalase and heme poisons, implicating
      H202 and myeloperoxidase in the cellular reaction. Aldehyde production by
      purified myeloperoxidase required H202 and chloride, and was mimicked by reagent
      hypochlorous acid (HOCl) in the absence of enzyme, suggesting that the reaction
      pathway involves a chlorinated intermediate. Collectively, these results indicate
      that the myeloperoxidase-H202-chloride system of phagocytes converts free hydroxy
      amino acids into highly reactive alpha-hydroxy and alpha,beta-unsaturated
      aldehydes. The generation of glycolaldehyde, 2-hydroxypropanal, and acrolein by
      activated phagocytes may thus play a role in AGE product formation and tissue
      damage at sites of inflammation.

PMID- 9022077
TI  - Inhibition of T cell apoptosis in the rheumatoid synovium.
AB  - Synovial T cells in rheumatoid arthritis are highly differentiated and express a
      phenotype suggesting susceptibility to apoptosis (CD45RB dull, CD45RO bright, Bcl
      2 low, Bax high, Fas high). However, no evidence of T cell apoptosis was found in
      synovial fluid from any of 28 patients studied. In contrast, synovial fluid from
      10 patients with crystal arthritis showed substantial levels of T cell apoptosis.
      The failre of apoptosis was not an intrinsic property of rheumatoid synovial T
      cells, as they showed rapid spontaneous apoptosis on removal from the joint.
      Synovial T cells from rheumatoid arthritis and gout patients could be rescued
      from spontaneous apoptosis in vitro either by IL-2R gamma chain signaling
      cytokines (which upregulate Bcl-2 and Bcl-XL) or by interaction with synovial
      fibroblasts (which upregulates Bcl-xL but not Bcl-2). The phenotype of rheumatoid
      synovial T cells ex vivo (Bcl-2 low, Bcl-xL high) suggested a fibroblast-mediated
      mechanism in vivo. This was confirmed by in vitro culture of synovial T cells
      with fibroblasts which maintained the Bcl-xL high Bcl-2 low phenotype. Synovial T
      cells from gout patients were Bcl-2 low Bcl-xL low and showed clear evidence of
      apoptosis in vivo. Inhibition experiments suggested that an integrin-ligand
      interaction incorporating the Arg-Gly-Asp motif is involved in fibroblast
      mediated synovial T cell survival. We propose that environmental blockade of cell
      death resulting from interaction with stromal cells is a major factor in the
      persistent T cell infiltration of chronically inflamed rheumatoid synovium.

PMID- 9022079
TI  - Increased accumulation of the glycoxidation product N(epsilon)
      (carboxymethyl)lysine in human tissues in diabetes and aging.
AB  - N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification
      of glycated proteins, has been suggested to represent a general marker of
      oxidative stress and long-term damage to proteins in aging, atherosclerosis, and
      diabetes. To investigate the occurrence and distribution of CML in humans an
      antiserum specifically recognizing protein-bound CML was generated. The oxidative
      formation of CML from glycated proteins was reduced by lipoic acid,
      aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and
      desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney,
      intestine, intervertebral discs, and particularly in arteries provided evidence
      for an age-dependent increase in CML accumulation in distinct locations, and
      acceleration of this process in diabetes. Intense staining of the arterial wall
      and particularly the elastic membrane was found. High levels of CML modification
      were observed within atherosclerotic plaques and in foam cells. The preferential
      location of CML immunoreactivity in lesions may indicate the contribution of
      glycoxidation to the processes occurring in diabetes and aging. Additionally, we
      found increased CML content in serum proteins in diabetic patients. The strong
      dependence of CML formation on oxidative conditions together with the increased
      occurrence of CML in diabetic serum and tissue proteins suggest a role for CML as
      endogenous biomarker for oxidative damage.

PMID- 9022078
TI  - Differential human multiple myeloma cell line responsiveness to interferon-alpha.
      Analysis of transcription factor activation and interleukin 6 receptor
      expression.
AB  - Although IFN-alpha is commonly used as maintenance treatment for multiple myeloma
      patients, its effectiveness is varied. In this study, we have used a panel of IL
      6 responsive myeloma cell lines that vary remarkably in responsiveness to IFN
      alpha. Three cell lines were growth arrested by IFN-alpha; however, IFN-alpha
      significantly stimulated growth of the fourth cell line, KAS-6/1. Our studies
      have focused on elucidating the mechanism of differential IFN-alpha
      responsiveness. First, we have shown that IFN-alpha-stimulated growth of the KAS
      6/1 cells did not result from induction of autocrine IL-6 expression. Second,
      analysis of Stats 1, 2, and 3 and IFN regulatory factor-1 (IRF-1) and IRF-2
      activation failed to reveal differences between the IFN-alpha growth-arrested or
      growth-stimulated cells. Third, although IFN-alpha treatment of the IFN-alpha
      growth-inhibited cell lines reduced IL-6 receptor (IL-6R) expression, IFN-alpha
      also reduced KAS-6/1 IL-6R expression. Finally, although IFN-alpha treatment
      reduced IL-6R numbers on each cell line, analysis of Stat protein activation
      revealed that the receptors were still functional. We conclude that myeloma cell
      responsiveness to IFN-alpha is heterogeneous and that mechanisms of IFN-alpha
      mediated growth inhibition other than IL-6R downregulation must exist in myeloma.
      Identification of these mechanisms may allow development of agents that are more
      universally effective than IFN-alpha.

PMID- 9022080
TI  - Active stage of autoimmune diabetes is associated with the expression of a novel
      cytokine, IGIF, which is located near Idd2.
AB  - Recently, interferon-gamma-inducing-factor (IGIF) has been described as a novel
      monokine that is a more potent interferon-gamma (IFN-gamma) inducer than IL-12.
      By cloning IGIF from affected tissue and studying IGIF gene expression, we
      describe for the first time a close association of this cytokine with an
      autoimmune disease. The non-obese diabetic (NOD) mouse spontaneously develops
      autoimmune insulitis and diabetes which can be accelerated and synchronized by a
      single injection of cyclophosphamide. IGIF mRNA was demonstrated by reverse
      transcriptase PCR in NOD mouse pancreas during early stages of insulitis. Levels
      of IGIF mRNA increased rapidly after cyclophosphamide treatment and preceded a
      rise in IFN-gamma mRNA, and subsequently diabetes. Interestingly, these kinetics
      mimick that of IL-12p40 mRNA, resulting in a close correlation of individual mRNA
      levels. Cloning of the IGIF cDNA from pancreas RNA followed by sequencing
      revealed identity with the IGIF sequence cloned from Kupffer cells and in vivo
      preactivated macrophages. When extending our study to macrophages of the spleen
      we observed that NOD mouse macrophages responded to cyclophosphamide with IGIF
      gene expression while macrophages from Balb/c mice treated in parallel did not.
      The IGIF gene position is located within the Idd2 interval on mouse chromosome 9
      and therefore it is a candidate for the Idd2 susceptible gene. We conclude that
      IGIF expression is abnormally regulated in autoimmune NOD mice and closely
      associated with diabetes development.

PMID- 9022081
TI  - Molecular and mutation trends analyses of omp1 alleles for serovar E of Chlamydia
      trachomatis. Implications for the immunopathogenesis of disease.
AB  - Serovars E, F, and D are the most prevalent Chlamydia trachomatis strains
      worldwide. This prevalence may relate to epitopes that enhance infectivity and
      transmission. There are numerous major outer membrane protein (MOMP) gene (omp1)
      variants described for D and F but few for E. However, omp1 constant regions are
      rarely sequenced yet, they may contain mutations that affect the
      structure/function relationship of the protein. Further, differentiating variants
      that occur as a result of selection from variants that contain random mutations
      without biologic impact is difficult. We investigated 67 urogenital E serovars
      and found 11 (16%) variants which contained 16 (53%) nonconservative amino acid
      changes. Using signature-pattern analysis, 57 amino acids throughout MOMP
      differentiated the E sequence set from the non-E sequence set, thus defining E
      strains. Four E variants did not match this signature-pattern, and, by phenetic
      analyses, formed new phylogenetic branches, suggesting that they may be
      biologically distinct variants. Our analyses offer for the first time a unique
      approach for identifying variants that may occur from selection and may affect
      infectivity and transmission. Understanding the mutation trends, phylogeny, and
      molecular epidemiology of E variants is essential for designing public health
      control interventions and a vaccine.

PMID- 9022082
TI  - Immunologic and hematopoietic effects of CD40 stimulation after syngeneic bone
      marrow transplantation in mice.
AB  - CD40 is a molecule present on multiple cell types including B lymphocyte lineage
      cells. CD40 has been shown to play an important role in B cell differentiation
      and activation in vitro, although little is known concerning the effects of CD40
      stimulation in vivo. We therefore examined the effects of CD40 stimulation in
      mice using a syngeneic bone marrow transplantation (BMT) model in an effort to
      augment B cell recovery after high dose therapy with hematopoietic
      reconstitution. After the BMT, mice were treated with or without 2-6 microg of a
      soluble recombinant murine CD40 ligand (srmCD40L) given intraperitoneally twice a
      week. A significant increase in B cell progenitors (B220+/ surface IgM-) was
      observed in the bone marrow of mice receiving the srmCD40L. The treated
      recipients also demonstrated improved B-cell function with increases in total
      serum immunoglobulin and increased splenic mitogen responsiveness to LPS being
      noted. Additionally, srmCD40L treatment promoted secondary lymphoid organ
      repopulation, accelerating germinal center formation in the lymph nodes. Total B
      cell numbers in the periphery were not significantly affected even with
      continuous srmCD40L administration. Lymphocytes obtained from mice treated with
      the ligand also had increases in T cell mitogen and anti-CD3 mAb responsiveness
      and acquired the capability to produce IL-4. Surprisingly, treatment with
      srmCD40L also produced hematopoietic effects in mice, resulting in an increase of
      BM and splenic hematopoietic progenitor cells in the mice after BMT. Treatment
      with srmCD40L significantly increased granulocyte and platelet recovery in the
      peripheral blood. Incubation of BMC with srmCD40L in vitro also resulted in
      increased progenitor proliferation, demonstrating that the hematopoietic effects
      of the ligand may be direct. Thus, stimulation of CD40 by its ligand may be
      beneficial in accelerating both immune and hematopoietic recovery in the setting
      of bone marrow transplantation.

PMID- 9022083
TI  - Retinoic acid inhibits the regulated expression of vascular cell adhesion
      molecule-1 by cultured dermal microvascular endothelial cells.
AB  - The regulated expression of cell adhesion molecules (CAM) on endothelial cells is
      central to the pathogenesis of various inflammatory processes. Retinoic acid and
      synthetic derivatives have been demonstrated to exert antiinflammatory effects in
      cutaneous diseases. To determine modes of retinoid action in the modulation of
      inflammatory responses, we explored effects of all-trans-retinoic acid (t-RA) on
      the TNFalpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1),
      intercellular adhesion molecule-1 (ICAM-1), and E-selectin in cultured human
      dermal microvascular endothelial cells. Pretreatment with t-RA specifically
      prevented TNFalpha-induced VCAM-1 expression, but not ICAM-1 and E-selectin
      induction. t-RA significantly reduced VCAM-1-dependent T cell binding to TNFalpha
      treated human dermal microvascular endothelial cells as well. This differential
      modulation of TNFalpha-induced CAM expression by t-RA was reflected at steady
      state mRNA levels and in nuclear run-on studies. In transcriptional activation
      studies, the TNFalpha-mediated activation of the human VCAM-1 promoter was
      inhibited after t-RA treatment, while the ICAM-1 promoter activation was
      unaffected, indicating that the selective inhibition of CAM expression is
      regulated in part at the level of gene transcription. Furthermore, the
      transcriptional inhibition by t-RA appears to be mediated by its effects upon the
      activation of NF-kappaB-dependent complex formation. Analysis of protein-DNA
      binding assays revealed marked inhibition of specific NF-kappaB-dependent binding
      to the tandem NF-KB sites of the VCAM-1 promoter, but not to the functional NF
      kappaB motif of the ICAM-1 promoter. The specific inhibition of cytokine-mediated
      VCAM-1 gene expression in vitro may provide a potential basis by which retinoids
      exert their biological effects at sites of inflammation in vivo.

PMID- 9022084
TI  - The exchange between proglycogen and macroglycogen and the metabolic role of the
      protein-rich glycogen in rat skeletal muscle.
AB  - The aim of this study is to determine if proglycogen and macroglycogen are
      kinetically related in rat skeletal muscle. Eight groups of anesthetized fasted
      rats (seven hepatic-occluded and one nonoccluded) were intravenously infused with
      [3-3H]glucose at a rate of 1.7 microCi x min(-1) for 20 min. At the end of
      infusion, hindlimb muscles were excised and rapidly frozen in liquid nitrogen.
      Proglycogen was extracted by precipitation in 10% TCA; and macroglycogen as a
      part of total glycogen by precipitation in 20% KOH-65% ethanol. Along with the
      tracer, the occluded rats were also infused with: saline (group 1); insulin at
      rates ranging from 5 to 50 mU x min(-1) (groups 2 to 5); and insulin at a rate of
      10 mU x min(-1) plus glucose at rates of 10.2 and 20.4 micromol x min(-1),
      respectively (groups 6 and 7). The infusion regimens resulted in up to 30-fold
      difference in whole-body glucose utilization among the rats. In the rats infused
      with saline and insulin at a rate of 5 mU x min(-1), [3H]glucose was found to be
      exclusively incorporated into proglycogen. Incorporation into macroglycogen was
      found in the rats infused with insulin at rates > 10 mU x min(-1). Supplementary
      glucose infusion increased the synthesis of [3H]proglycogen (four- to sixfold),
      and equilibrated the two extractable forms of glycogen in the insulin-infused
      rats. In the saline-infused nonoccluded rats, only proglycogen was found to be
      labeled. In conclusion, our data indicate that in the intact and hepatic-occluded
      rats, proglycogen in the skeletal muscles may undergo synthesis and degradation
      of its own more readily than exchange between itself and depot macroglycogen.

PMID- 9022085
TI  - A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat
      pancreatic secretion.
AB  - The mechanisms by which short-term ethanol administration alters pancreatic
      exocrine function are unknown. We have evaluated the effects of ethanol
      administration on pancreatic secretion of digestive enzymes. In our studies,
      anesthetized as well as conscious rats were given ethanol at a rate sufficient to
      cause the blood ethanol concentration to reach levels associated with clinical
      intoxication. Ethanol was administered over a 2-h period during which blood
      ethanol levels remained stably elevated. We report that intravenous
      administration of ethanol results in a transient increase in pancreatic amylase
      output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in
      amylase output can be completely inhibited by the CCK-A receptor antagonist L
      364,718 and partially inhibited by the muscarinic cholinergic antagonist
      atropine. The ethanol-induced rise in amylase output can be completely prevented
      by instillation of trypsin into the duodenum or by lavage of the duodenum with
      saline during ethanol administration. Furthermore, the intraduodenal activity of
      a CCK-releasing factor is increased by infusion of ethanol. These studies
      indicate that administration of ethanol causes rat pancreatic exocrine secretion
      to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing
      factor which is present within the duodenal lumen. These observations lead us to
      speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic
      digestive enzyme secretion may play a role in the events which link ethanol abuse
      to the development of pancreatic injury.

PMID- 9022086
TI  - Activation of large conductance potassium channels inhibits the afferent and
      efferent function of airway sensory nerves in the guinea pig.
AB  - Sensory nerves play an important role in airway disease by mediating central
      reflexes such as cough, and local axon reflexes resulting in the peripheral
      release of neuropeptides. We have tested whether the benzimidazolone compound,
      NS1619, an opener of large conductance calcium-activated potassium (BK Ca)
      channels, inhibits the activity of sensory fibers, and central and local airway
      reflexes in guinea pig airways. In in vitro single fiber recording experiments,
      NS1619 applied to identified receptive fields in the trachea inhibited the firing
      of A(delta)-fibers evoked by hypertonic saline and distilled water, and
      bradykinin-evoked firing of C-fibers. Electrically evoked nonadrenergic
      noncholinergic contractions of isolated bronchi mediated by the release of
      neurokinin A (NKA) from C-fibers, but not those elicited by exogenous NKA, were
      inhibited by NS1619. These effects of NS1619 were prevented by iberiotoxin, a
      selective blocker of BK Ca channels. In conscious guinea pigs, cough evoked by
      aerosolized citric acid was also inhibited by NS1619. These data show that BK Ca
      channel activation inhibits sensory nerve activity, resulting in a reduction of
      both afferent and efferent function. BK Ca channel openers may therefore be of
      potential benefit in reducing neurogenic inflammation and central reflexes seen
      during inflammatory conditions of the airways, and may represent a new class of
      antitussive drug.

PMID- 9022087
TI  - Alternative expression of platelet glycoprotein Ib(beta) mRNA from an adjacent 5'
      gene with an imperfect polyadenylation signal sequence.
AB  - Glycoprotein (GP) Ib is a major component of the platelet membrane receptor for
      von Willebrand factor, designated the GP Ib-IX-V complex. GP Ib is composed of
      two subunits (GP Ib(alpha) and GP Ib(beta)) each synthesized from separate genes.
      The 206 amino acid precursor of GP Ib(beta) is synthesized from a 1.0-kb mRNA
      expressed by megakaryocytes and was originally characterized from cDNA clones of
      human erythroleukemic (HEL) cell mRNA, a cell line exhibiting megakaryocytic-like
      properties. The cell line CHRF-288-11 also exhibits megakaryocytic-like
      properties, but synthesizes two related GP Ib(beta) mRNA species of 3.5 and 1.0
      kb. We performed cDNA cloning experiments to identify the origin of the 3.5-kb
      transcript and determine its relationship to the 1.0-kb GP Ib(beta) mRNA found in
      megakaryocytes, platelets, and HEL cells. Our cloning experiments demonstrate
      that the longer transcript results from a nonconsensus polyadenylation
      recognition sequence, 5'AACAAT3', within a separate gene located upstream to the
      platelet GP Ib(beta) gene. In the absence of normal polyadenylation the more 5'
      gene uses the polyadenylation site within its 3' neighbor, the platelet GP
      Ib(beta) gene. This newly identified 5' gene contains an open reading frame
      encoding 369 amino acids with a high degree of sequence similarity to an
      expanding family of GTP-binding proteins.

PMID- 9022088
TI  - Neutrophil margination, sequestration, and emigration in the lungs of L-selectin
      deficient mice.
AB  - These studies tested the hypothesis that L-selectin plays a role in neutrophil
      traffic in the lungs, particularly in neutrophil margination, sequestration, and
      emigration, using L-selectin-deficient mice. No defect in neutrophil margination
      within either capillaries or arterioles and venules was observed in uninflamed
      lungs of L-selectin-deficient mice. The initial rapid sequestration of
      neutrophils within the pulmonary capillaries 1 min after intravascular injection
      of complement fragments was not prevented. In contrast, L-selectin did contribute
      to the prolonged neutrophil sequestration (> or = 5 min). Interestingly,
      neutrophil accumulation within noncapillary microvessels required L-selectin at
      both 1 and 5 min after complement injection. During bacterial pneumonias, L
      selectin played a role in neutrophil accumulation within noncapillary
      microvessels in response to either Escherichia coli or Streptococcus pneumoniae
      and within capillaries in response to E. coli but not S. pneumoniae. However, L
      selectin was not required for emigration of neutrophils or edema in response to
      either organism. These studies demonstrate a role for L-selectin in the prolonged
      sequestration of neutrophils in response to intravascular complement fragments,
      in the intracapillary accumulation of neutrophils during E. coli-induced
      pneumonia, and in the accumulation of neutrophils within noncapillary
      microvessels when induced by either intravascular complement fragments or

PMID- 9022089
TI  - Differentiation of glucose toxicity from beta cell exhaustion during the
      evolution of defective insulin gene expression in the pancreatic islet cell line,
      HIT-T15.
AB  - Chronic exposure of HIT-T15 cells to supraphysiologic glucose concentration
      diminishes insulin gene expression and decreased binding of two critical insulin
      gene transcription factors, STF-1 and RIPE-3b1 activator. To distinguish whether
      these changes are caused by glucose toxicity or beta cell exhaustion, HIT-T15
      cells grown from passage 75 through 99 in media containing 11.1 mM glucose were
      switched to 0.8 mM glucose at passage 100. They regained binding of STF-1 and
      RIPE-3b1 activator and had a partial but minimal return of insulin mRNA
      expression. In a second study, inclusion of somatostatin in the media-containing
      11.1 mM glucose inhibited insulin secretion; however, despite this protection
      against beta cell exhaustion, dramatic decreases in insulin gene expression, STF
      1 and RIPE-3b1 binding, and insulin gene promoter activity still occurred. These
      data indicate that the glucotoxic effects caused by chronic exposure to
      supraphysiologic concentration of glucose are only minimally reversible and that
      they are not due simply to beta cell exhaustion. These observations carry with
      them the clinical implication that Type II diabetic patients who remain
      hyperglycemic for prolonged periods may have secondary glucose toxic effects on
      the beta cell that could lead to defective insulin gene expression and worsening
      of hyperglycemia.

PMID- 9022091
TI  - Bilateral nonarteritic anterior ischemic optic neuropathy.

PMID- 9022090
TI  - Nitric oxide (NO) modulates the neurogenic control of blood pressure in rats with
      chronic renal failure (CRF).
AB  - Increased sympathetic nervous system (SNS) activity plays a role in the genesis
      of hypertension in rats with chronic renal failure (CRF). Because nitric oxide
      (NO) modulates the activity of the SNS, a deficit of NO synthesis could be
      responsible for the increased SNS activity in these animals. In the present
      study, we evaluated the effects of L-arginine and L-NAME on blood pressure and
      SNS activity-in Sprague Dawley 5/6 nephrectomized or sham-operated rats. SNS
      activity was determined by measuring norepinephrine turnover rate in several
      brain nuclei involved in the regulation of blood pressure. In the same brain
      nuclei, we measured NO content and nitric oxide synthase (NOS) gene expression by
      semiquantitative measurements of NOS mRNA reverse transcription polymerase chain
      reaction. In CRF rats, norepinephrine turnover rate was increased in the
      posterior hypothalamic nuclei, locus coeruleus, paraventricular nuclei, and the
      rostral ventral medulla, whereas NOS mRNA gene expression and NO2/NO3 content
      were increased in all brain nuclei tested. L-NAME increased blood pressure and NE
      turnover rate in several brain nuclei of both control and 5/6 nephrectomized
      rats. In CRF rats, a significant relationship was present between the percent
      increment in NOS mRNA gene expression related to the renal failure, and the
      percent increase in norepinephrine turnover rate caused by L-NAME. This suggests
      that endogenous NO may partially inhibit the activity of the SNS in brain nuclei
      involved in the neurogenic regulation of blood pressure, and this inhibition is
      enhanced in CRF rats. In summary, the increase in SNS activity in the posterior
      hypothalamic nuclei and in the locus coeruleus of CRF rats is partially mitigated
      by increased local expression of NOS m-RNA.

PMID- 9022092
TI  - Silicone frontalis slings for correction of blepharoptosis.

PMID- 9022093
TI  - Canalicular function after "one-stitch" repair.

PMID- 9022094
TI  - Surface characterization of intraocular lenses.

PMID- 9022095
TI  - Usage of "pathology".

PMID- 9022096
TI  - Tasks performed by certified ophthalmic medical personnel.

PMID- 9022097
TI  - More pieces for the age-related macular degeneration puzzle.

PMID- 9022098
TI  - The five-year incidence and progression of age-related maculopathy: the Beaver
      Dam Eye Study.
AB  - PURPOSE: The aim of the study was to describe the incidence and progression of
      retinal drusen, retinal pigmentary abnormalities, and signs of late age-related
      maculopathy. POPULATION: A population of 3583 adults (range, 43-86 years of age
      at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period.
      METHODS: Characteristics of drusen and other lesions typical of age-related
      maculopathy were determined by grading stereoscopic color fundus photographs
      using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: There was a
      statistically significant increased incidence of age-related maculopathy lesions
      with age (P < 0.05). Individuals 75 years of age or older had a significantly (P
      < 0.01) higher 5-year incidence of the following characteristics than people 43
      to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or =
      250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal
      pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs.
      0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the
      incidence of early age-related maculopathy was 2.2 times (95% confidence interval
      1.6, 3.2) as likely in women 75 years of age or older compared with men this age.
      At follow-up, late age-related macular degeneration was more likely to develop in
      eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary
      abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions.
      CONCLUSIONS: These population-based estimates document the high incidence of
      signs of age-related maculopathy in people 75 years of age or older, and in women
      compared with men that age. The findings demonstrate that the presence of soft
      drusen and pigmentary abnormalities significantly increases the risk for the
      development of geographic atrophy and exudative macular degeneration.

PMID- 9022099
TI  - Surgical removal of subfoveal choroidal neovascularization in presumed ocular
      histoplasmosis: stability of early visual results.
AB  - PURPOSE: The authors assess the stability of visual acuity outcomes after the
      surgical removal of subfoveal choroidal neovascularization in a large series of
      patients with presumed ocular histoplasmosis syndrome (POHS). METHODS: A
      retrospective study of 117 consecutive patients undergoing vitrectomy between
      February 1990 and December 1994 was performed. All patients underwent the
      surgical removal of subfoveal choroidal neovascularization due to POHS and had at
      least 3 months of follow-up. Postoperative Snellen visual acuity was the primary
      study endpoint. RESULTS: With a median follow-up of 13 months (range, 3-46
      months), 35% of patients had postoperative visual acuity of 20/40 or better, and
      40% had improvement of three or more Snellen lines after surgery. In a subset of
      54 eyes followed for at least 1 year, 91% showed stable or improved vision
      between the 3- and 12-month time points, and 85% showed stable or improved vision
      between 3 months and final visit. CONCLUSION: Follow-up of a large number of
      patients appears to confirm initially encouraging results and to suggest
      stability of beneficial effect after the surgical removal of subfoveal choroidal
      neovascularization in POHS.

PMID- 9022100
TI  - Retinal detachment after branch retinal vein occlusion: influence of the type of
      break on the outcome of vitreous surgery.
AB  - BACKGROUND: Branch retinal vein occlusion (BRVO) is occasionally complicated by
      two types of retinal breaks (retinal holes without vitreous traction or retinal
      traction tears) that may lead to a rhegmatogenous retinal detachment (RRD). The
      authors describe surgical results of vitrectomy for RRD after BRVO and
      investigate whether there is any difference between clinical features or surgical
      results from eyes with the two types of retinal breaks. PATIENTS AND METHODS: The
      authors retrospectively studied 25 patients (25 eyes) who underwent vitrectomy
      for RRD after BRVO. Twelve of 25 eyes (48%) had a detachment secondary to one or
      more retinal holes (group I), and 13 of the eyes (52%) had one or more retinal
      tears (group II). RESULTS: Seventeen of the eyes (68%) achieved total retinal
      reattachment after the initial surgery; 22 (88%) did so by the time of final
      examination. Patients with retinal holes achieved more favorable final vision
      than those with retinal tears (P = 0.0391). A higher rate of preoperative macular
      detachment (P = 0.0112) and a higher rate of recurrent retinal detachment after
      initial vitrectomy (P = 0.0302) were the factors associated with the reduced
      final visual acuity in patients with retinal tears. The increased rate of
      recurrent retinal detachment in patients with retinal tears was associated with a
      higher rate of existing preretinal neovascular membranes (P = 0.0112) and a trend
      toward an increased incidence of intraoperative iatrogenic retinal breaks.
      CONCLUSION: Among patients who undergo vitrectomy for RRD after BRVO, better
      surgical results are expected in eyes with retinal holes without vitreous
      traction than in those with retinal traction tears. This difference is thought to
      be due to the difference in vitreoretinal anatomy between eyes with the two types
      of retinal breaks.

PMID- 9022101
TI  - Perifoveal capillary network in patients with acute central retinal vein
      occlusion.
AB  - PURPOSE: Reduction of visual acuity in patients with central retinal vein
      occlusion (CRVO) is often caused by macular edema and ischemia. The major
      causative factor for macular changes may be a disturbance in the macular
      microcirculation. The authors studied the perifoveal microcirculation in patients
      with central retinal vein occlusion to quantify the extent of circulatory
      deficiency in the macular circulation. METHODS: Twenty-four patients (8 men, 16
      women) with recently diagnosed CRVO were included in this study. The following
      data were quantified: mean capillary blood velocity (CBV), foveal avascular zone
      (FAZ), and mean perifoveal intercapillary area (PIA). RESULTS: In patients with
      CRVO, the mean flow velocity was significantly reduced compared with healthy
      subjects (1.63 +/- 0.220 mm/sec vs. 2.89 +/- 0.41 mm/sec, P < 0.01). The FAZ and
      the mean PIA characterizing capillary density were significantly enlarged in CRVO
      (5548 +/- 1151 microm2 vs. 3872 +/- 529 microm2; P < 0.01). CONCLUSIONS: The
      present study demonstrates that CRVO not only led to a decrease in capillary
      blood velocities, but also to an enlargement of perifoveal intercapillary areas
      in early stages of the disease.

PMID- 9022102
TI  - Congenital malignant teratoid neoplasm of the eye and orbit: a case report and
      review of the literature.
AB  - BACKGROUND: Medulloepithelioma is a tumor of the primitive medullary epithelium
      overlying the ciliary body. Most become evident early in life, and they may be
      malignant, although distant metastases are rare. The purpose of this report is to
      describe a unique case of congenital malignant teratoid neoplasm of the eye and
      orbit. METHOD: A patient with a congenital malignant teratoid tumor of the eye
      and orbit is described, and a detailed histopathologic study of the ocular
      findings with a review of the literature is presented. RESULTS: Histopathologic
      study showed that the lesion was a malignant teratoid neoplasm with a large
      orbital extension. Several intracranial structural abnormalities were identified.
      CONCLUSION: The tumor described herein must be added to the differential
      diagnosis of congenital orbital masses. The clinician should be alert to the
      association of this lesion with complex intracranial abnormalities.

PMID- 9022103
TI  - Unilateral retinoblastoma in an adult: report of a case and review of the
      literature.
AB  - PURPOSE: The authors report the clinical, cytologic, and histopathologic findings
      of a unilateral retinoblastoma occurring in a 26-year-old woman. This tumor
      usually affects young children; the mean age at the time of diagnosis usually
      ranges from 10 to 25 months. METHODS: Histopathologic examination of the
      enucleated right eye included using standard techniques, as well as
      immunohistochemical stains of formalin-fixed, paraffin-embedded tissues. RESULTS:
      Histologic examination of sections of the eye showed a retinal tumor that was
      centered in the equatorial region and had the typical features of a poorly
      differentiated retinoblastoma. Focal choroidal invasion and seeding of the
      anterior and posterior chambers were observed. Immunoreactivity of the tumor
      cells for neuron-specific enolase confirmed that the tumor is a neuronal neoplasm
      consistent with retinoblastoma. CONCLUSION: Retinoblastoma occurring in adults is
      a rare finding. In most large series of retinoblastomas, no adults are included.
      Only eight patients 20 years of age or older with retinoblastomas have been
      documented previously. In the current case, the patient had no evidence of
      orbital recurrence or metastasis 6 years after enucleation of the eye. It may be
      important for clinicians to consider this diagnosis when confronted with a
      retinal mass of unknown etiology in adults.

PMID- 9022104
TI  - Atypical, severe toxoplasmic retinochoroiditis in elderly patients.
AB  - BACKGROUND: The diagnosis of toxoplasmic retinochoroiditis is based primarily on
      characteristic ocular findings, with supportive serologic evidence. Clinical
      recognition of atypical presentations is critical for timely antiparasitic drug
      therapy. METHODS: Case histories were reviewed for seven presumed immunocompetent
      elderly patients with atypically severe (multifocal or diffuse or both)
      toxoplasmic retinochoroiditis. Three cases initially were misdiagnosed as acute
      retinal necrosis syndrome. The correct diagnosis was confirmed in each case by
      response to antiparasitic drug therapy, polymerase chain reaction studies of
      intraocular specimens, or histopathologic analysis. RESULTS: The patients ranged
      in age from 69 to 82 years (median, 74 years). Only three patients had
      intercurrent medical conditions that may be associated with subtle immune
      dysfunction (diabetes mellitus and hepatitis C). The extensive necrotizing
      retinochoroiditis in each patient was nonhemorrhagic and not associated with
      occlusive retinal arteritis. Despite prompt response to antiparasitic drug
      therapy, prolonged treatment usually was required, and four patients had
      retinitis reactivation after discontinuing treatment. Significant visual loss
      accompanied the infection in most eyes. CONCLUSION: Toxoplasmosis should be
      considered as a cause of multifocal or diffuse necrotizing retinitis or both in
      elderly patients. Older patients may be more susceptible to severe ocular
      Toxoplasma infections because of age-related decline in cell-mediated immunity
      and chronic underlying diseases.

PMID- 9022105
TI  - Scleritis-associated uveitis.
AB  - PURPOSE: Anterior uveitis may accompany scleritis. This study was undertaken to
      analyze the incidence, characteristics, and meaning of uveitis in the course of
      scleritis. METHODS: Patient characteristics, scleritis type, ocular
      complications, and specific systemic diseases were evaluated in patients with
      scleritis-associated uveitis; comparisons were made between patients with
      scleritis-associated uveitis and patients with scleritis without uveitis.
      RESULTS: Seventy three (42%) of 172 patients with scleritis had anterior uveitis.
      Scleritis-associated uveitis ranged from mild to moderate intensity and always
      was related to the presence of active scleritis. Patients with scleritis
      associated uveitis had more necrotizing scleritis (37%, P = 0.0001), decrease in
      vision (49%, P = 0.0046), peripheral ulcerative keratitis (22%, P = 0.0095), and
      glaucoma (19%, P = 0.0313) than did patients with scleritis without uveitis.
      Patients with scleritis-associated uveitis did not have any specific associated
      systemic disease more often than did patients with scleritis without uveitis.
      CONCLUSION: Extension of scleral inflammation to the anterior uveal tract is a
      consequence of a more severe disease with possible ocular complications that may
      cause progressive visual loss. The occurrence of anterior uveitis in the course
      of scleritis entails a poor ocular prognosis. The authors believe, therefore,
      that the anterior uveal tract should be evaluated at every follow-up visit of a
      patient with scleritis, so that emergence of this important prognostic condition
      (anterior uveitis) may be detected promptly and systemic therapy instituted
      appropriately.

PMID- 9022107
TI  - Clear lensectomy and implantation of a low-power posterior chamber intraocular
      lens for correction of high myopia: a four-year follow-up.
AB  - PURPOSE: To evaluate the 4-year postoperative outcomes of patients who are highly
      myopic who underwent clear lensectomy via phacoemulsification and low power
      posterior chamber intraocular lens implantation. METHODS: The authors performed
      surgery in 52 eyes of 30 patients in which prophylactic retinal treatment, clear
      lensectomy, and posterior chamber intraocular lens implantation were used to
      treat high myopia of 12 diopters (D) or greater. A total of 49 eyes of 28
      patients were evaluated at the 4-year postoperative timeframe. Visual acuity,
      complications, and refractive stability were assessed. RESULTS: The incidence of
      retinal detachment through 4 years was 1.9%. No new macular complications were
      observed. Two patients had posterior vitreous detachment without clinical impact
      between 1 and 4 years after surgery. The incidence of neodymium:YAG (Nd:YAG)
      capsulotomy was 36.7%. The mean postoperative spherical equivalent was -0.92 D.
      Four patients had a myopic shift of 0.50 D to 1.00 D from the 1- to 4-year
      timeframe. Corrected visual acuity of 20/40 or better was achieved in 82% of eyes
      that had undergone Nd:YAG capsulotomy versus 56% of untreated eyes. Uncorrected
      visual acuity of 20/100 or better was achieved in 82% of eyes treated with the
      Nd:YAG laser versus 62% of untreated eyes. CONCLUSION: Visual acuity and
      refractive outcomes with clear lensectomy are favorable. Retinal detachment
      remains the major concern of this procedure. Continuous follow-up of these
      patients is necessary.

PMID- 9022106
TI  - Use of laser flare photometry to assess and monitor inflammation in uveitis.
AB  - PURPOSE: Laser flare photometry (LFP) is a new quantitative method for the
      evaluation of aqueous flare, making flare the only inflammatory parameter that
      can be evaluated precisely and objectively. The aim of this study was to
      characterize the inflammatory pattern of acute human leukocyte antigen-B27 (HLA
      B27)-related anterior uveitis and to determine further clinical use and
      limitations of LFP in posterior inflammation. METHODS: In the first part of the
      study, 78 episodes of HLA-B27-related acute anterior uveitis were analyzed to
      determine mean pretreatment (initial) flare, mean flare evolution, need for
      additional periocular steroids, and mean duration of an episode. In the second
      part of the study, the use of LFP was further tested in posterior inflammation,
      first by analyzing the predictive value of a subclinical LFP-detected flare
      increase for disease recrudescence in posterior scleritis, and then by exploring
      clinical applications for LFP in posterior uveitis, where LFP was essential
      either in the establishment of a diagnosis or in guiding therapeutic decisions.
      RESULTS: Mean initial flare in HLA-B27-related acute anterior uveitis was 160 +/-
      22 photons/msec, and mean duration of an episode was 18.5 +/- 15 days. A 50% and
      90% flare reduction occurred after 2 and 8 days, respectively. In posterior
      scleritis, LFP was accurate in monitoring response to systemic steroid therapy
      and a small flare increase was predictive for disease recrudescence in five of
      six cases (predictive value 0.83, sensitivity 100%). In posterior uveitis, LFP
      was sensitive to monitor systemic treatments and to establish a diagnosis in
      unclear cases by measuring the effect of a selective therapy (therapeutic trial)
      on the flare level. CONCLUSION: In acute anterior HLA-B27-associated uveitis, LFP
      represented a potential improvement in management by allowing precise adjustment
      of therapy. In uveitis of the posterior segment, our data confirm the validity of
      LFP to monitor response and adjust systemic therapy and to detect disease
      recurrence in patients with a sufficient pretreatment level of associated blood
      aqueous barrier disruption (flare).

PMID- 9022108
TI  - Ocular ultrasound in Alagille syndrome: a new sign.
AB  - BACKGROUND: Alagille syndrome (AS) is one of six forms of familial intrahepatic
      cholestasis, all of which present with neonatal jaundice and paucity of
      intrahepatic bile ducts. Differentiation of these individual syndromes is crucial
      as their treatments and prognoses vary. It is the ophthalmic features, posterior
      embryotoxon on particular, that distinguish AS. METHODS: The authors performed
      full ocular examination, including A- and B-scan ultrasound, refraction, and,
      where possible, fluorescein angiography in 20 unrelated children with AS and 8
      with non-AS-related cholestasis. RESULTS: There was ultrasound evidence of optic
      disc drusen in at least one eye in 95% and bilateral disc drusen in 80% of
      patients with AS but in none of the patients who were non-AS at the time of
      examination. Independent review of hard-copy scans suggested drusen in at least
      one eye in 90% of the cases and bilateral drusen in 50%, although this latter
      figure rose to 65% on review of the angiograms. This is markedly higher than the
      incidence in the normal population (0.3%-2%). Axial lengths were shorter than
      expected for the older age group (older than 10 years of age), but this was not
      associated with gross ametropia. CONCLUSION: This strong association of AS and
      optic disc drusen has not been reported previously and represents not only the
      first significant association between a systemic condition and disc drusen but
      also a possibly useful tool in the diagnosis of AS, especially in young children.

PMID- 9022110
TI  - Lower eyelid recession combined with ptosis surgery in patients with poor ocular
      motility.
AB  - BACKGROUND: The authors treated ten patients (13 eyelids) with visually
      significant blepharoptosis and compromised corneal protective mechanisms
      resulting from paresis of ocular motility and absent Bell phenomenon. METHODS:
      Traditional upper eyelid surgery consisting of frontalis suspension (6 eyelids)
      or levator aponeurosis advancement (7 eyelids) was used. In all patients, the
      ptosis repair was combined with maximum recession of the lower eyelid, using a
      posterior lamellar scleral spacer graft. The goal was to maintain a narrow,
      vertical, interpalpebral fissure to allow for eyelid closure, but to reposition
      this opening centrally over the pupil. RESULTS: Postoperatively, all patients
      achieved significant improvement in superior visual field, with no associated
      keratopathy. Complications were few, minor, and transient. The postoperative
      cosmetic appearance was acceptable in all patients. CONCLUSIONS: This combined
      procedure allows repair of fair- to poor-function ptosis in patients in whom
      ptosis surgery previously has been considered risky. For the authors, this
      technique has been proven safe and effective and should be considered in any
      patient population with compromised corneal protective mechanisms.

PMID- 9022109
TI  - Dacryocystorhinostomy with intraoperative mitomycin C.
AB  - PURPOSE: To observe the effect of intraoperative mitomycin C on the size of the
      osteotomy site after dacryocystorhinostomy.: METHODS: A total of 15 eyes of 14
      patients diagnosed with primary acquired nasolacrimal duct obstruction were
      assigned randomly to either a mitomycin C group or a control group. The surgical
      procedures in both groups were exactly the same, except that in the patients in
      the mitomycin C group, a piece of neurosurgical cottonoid soaked with 0.2 mg/ml
      mitomycin C was applied to the osteotomy site and then after 30 minutes was
      removed transnasally. Nasoendoscopic findings were recorded at the completion of
      the surgery and at 1 month, 3 months, and 6 months after surgery for the two
      groups. A computer-aided digitizer was used to calculate the surface area of the
      osteotomy site, and a Student's t test was used to compare the difference between
      the two groups. RESULTS: All patients in the mitomycin C group remained symptom
      free after removal of their silicone tube (100% success), and there was one
      patient in the control group who had recurrent epiphora (87.5% success). Septo
      osteotomy adhesion was found in two patients in the control group (25%), but
      there was no such adhesion found in the patients in the mitomycin C group. In the
      mitomycin C group, the average final surface area of the osteotomy at the end of
      the sixth postoperative month was 27.10 +/- 5.78 mm2, whereas that of the control
      group was only 10.83 +/- 3.37 mm2. Although the immediate postoperative surface
      area of the osteotomy showed no significant difference between the two groups, a
      statistically significant difference was noted at 6 months. CONCLUSION:
      Intraoperative mitomycin C is effective in maintaining a larger osteotomy size.
      This modification may possibly improve success rates over the traditional
      dacryocystorhinostomy procedure.

PMID- 9022111
TI  - Projectile metallic foreign bodies in the orbit: a retrospective study of
      epidemiologic factors, management, and outcomes.
AB  - PURPOSE: Intraorbital projectile metallic foreign bodies are associated with
      significant ocular and orbital injuries. The authors sought to evaluate
      epidemiologic factors, the incidence of associated ocular and orbital injury, and
      the nature and necessity of surgical intervention in these cases. METHODS: Charts
      of all patients with projectile intraorbital metallic foreign bodies seen at our
      institution (27) over the preceding 7 years were evaluated with respect to age,
      sex, type of injury, associated ocular and orbital injuries, location of the
      projectile (anterior, epibulbar, or posterior), postinjury visual acuity, and
      surgical intervention. RESULTS: The majority of patients were male, between the
      ages of 11 and 30, and had BB pellet injuries. Thirteen projectiles were lodged
      anteriorly, 4 were in an epibulbar position, and the remaining 10 were posterior
      to the equator. Twelve of 13 anterior, and 4 of 4 epibulbar foreign bodies were
      removed surgically, whereas only 2 of 10 posterior foreign bodies required
      surgery. No case of surgical intervention resulted in a decrease of visual
      acuity. Associated ocular injuries were both more common and severe in patients
      with posteriorly located foreign bodies. Final visual acuity was better at
      presentation and at discharge in patients with anteriorly located foreign bodies.
      CONCLUSION: Intraorbital projectile metallic foreign bodies can be a source of
      significant ocular morbidity. Management of these cases is dependent on the
      location of the projectile. Ancillary radiographic studies can be helpful.
      Surgery to remove the projectile should be considered in each case, but foreign
      bodies that are not readily accessible often may be left safely in place. Closer
      regulation of the pellet gun industry, with an emphasis on education and
      protective eyewear use, would be helpful in reducing these injuries.

PMID- 9022112
TI  - Comparison of visual function in fellow eyes after bilateral nonarteritic
      anterior ischemic optic neuropathy.
AB  - PURPOSE: Although previous studies have examined the risk of bilaterality of
      nonarteritic ischemic optic neuropathy (NAION), none have compared extensively
      the extent of visual loss between fellow eyes. The authors examined cases of
      bilateral NAION to determine the extent of vision loss in the second eye compared
      with that in the first eye. METHODS: Thirty-one cases of bilateral NAION were
      reviewed. Variables included age, gender, and the presence of comorbid disease.
      Visual function was assessed by Snellen visual acuity, color vision, and pattern
      and mean deviation of the visual fields. RESULTS: No correlation was detected
      between the extent or pattern of visual loss in fellow eyes. No significant
      difference in visual function existed between first and second eyes for the
      patients overall. Patients who retained better visual function in the second eye
      were significantly older than those who retained better visual function in the
      first eye (visual acuity, P = 0.0005; color vision, P = 0.07; mean deviation, P =
      0.02). In patients older than 50 years of age (25 of 31 cases), the second eye
      had significantly better visual acuity (P = 0.04) and less Humphrey visual field
      mean deviation (P = 0.04) than the first eye. CONCLUSION: Visual function in the
      second eye correlated poorly with that of the first eye. Older patients with
      bilateral NAION retained better visual function in the second eye than in the
      first eye. For younger patients, the extent of visual loss in the second eye
      could not be predicted based on the visual loss in the first eye.

PMID- 9022113
TI  - The association of strabismus, amblyopia, and refractive errors in spasmus
      nutans.
AB  - PURPOSE: Spasmus nutans is a condition that includes asymmetric nystagmus and
      occurs during the amblyogenic period. Because specific alterations in early
      visual experience are known to be associated with changes in visual development,
      relations between spasmus nutans and abnormal visual sequelae were examined.
      METHODS: The records of 18 patients with spasmus nutans were reviewed
      retrospectively. The incidence of strabismus, amblyopia, anisometropia, and
      astigmatism was compared with published age-matched control subjects. RESULTS:
      There was a significantly higher incidence of strabismus (10 of 18) and amblyopia
      (8 of 18) of the eye with the greater amplitude of nystagmus. No correlation of
      refractive error with lateralization of nystagmus could be established. Twelve of
      18 patients required spectacles for improvement in visual acuity and for
      treatment of amblyopia. Best-corrected visual acuity averaged 1.20 Snellen lines
      poorer than age-adjusted normative values; however, loss of visual acuity was, in
      most cases, symmetric and not related to lateralization of nystagmus. CONCLUSION:
      Early detection and treatment of anticipated abnormal visual issues in patients
      with spasmus nutans will optimize visual outcomes.

PMID- 9022114
TI  - Delay of corneal wound healing in patients treated with colchicine.
AB  - BACKGROUND: Colchicine has a known adverse effect on wound healing through its
      inhibitory effect on tubulin-dependent cell functions and through collagenase
      activation. In the cornea, it has been shown in animal and in vitro studies to
      inhibit epithelium mitosis, fibroblast mitosis and migration, as well as to
      reduce collagen deposition. The authors report on two patients with corneal
      ulcers refractory to conventional treatment while the patients were undergoing
      oral colchicine therapy. CASE REPORTS: The first patient was an 86-year-old woman
      who had been treated with oral colchicine because of rheumatoid arthritis. She
      was admitted to the authors' department with a deep corneal ulcer in the right
      eye for which she had been treated for 3 weeks with local antibiotics without any
      improvement. The second patient, a 60-year-old woman, was hospitalized because of
      a corneal ulcer in her left eye. She had been receiving oral colchicine therapy
      for mixed connective tissue disease. Treatment with local antibiotics was
      initiated but the condition of the eye worsened, ultimately resulting in corneal
      perforation. RESULTS: Withdrawal of oral colchicine therapy was followed by rapid
      corneal wound healing in both patients. CONCLUSION: The findings in these two
      patients suggest that colchicine may delay corneal wound healing. The authors
      suggest that in patients with corneal ulcers refractory to conventional treatment
      who are receiving colchicine, cessation of colchicine therapy should be
      considered.

PMID- 9022115
TI  - Herpes simplex virus keratitis among patients who are positive or negative for
      human immunodeficiency virus: an epidemiologic study.
AB  - PURPOSE: The authors compare the incidence and clinical course of herpes simplex
      virus (HSV) keratitis among patients who are positive and negative for human
      immunodeficiency virus (HIV). METHODS: A retrospective cohort study was designed.
      Outcomes measured in both groups included incidence of HSV keratitis, lesion type
      (epithelial vs. stromal), lesion location (central vs. peripheral), treatment
      time, time to first recurrence, and recurrence rate. RESULTS: There was no
      statistically significant difference between the groups for any of the outcomes
      measured except for recurrence rate. The recurrence rate was 2.48 times more
      frequent among patients positive for HIV (1 recurrence per 587 person-days of
      follow-up among patients positive for HIV vs. 1 per 1455 person-days among
      patients negative for HIV). CONCLUSIONS: Except for recurrence rate, the
      incidence and clinical course of HSV keratitis in this study were no different
      among patients positive and negative for HIV.

PMID- 9022116
TI  - Detection of antichlamydial antibodies in tears: a diagnostic aid?
AB  - OBJECTIVES: The antibody response in sera and tears of 167 patients with
      suspected chlamydial conjunctivitis was compared with the antibody response in
      sera and tears of 45 patients with symptoms of urogenital chlamydial infection to
      discover whether and which type of antichlamydial antibody detected in tears may
      be of diagnostic help in chlamydial conjunctivitis. METHODS: Diagnosis was based
      on chlamydial antigen detection from the conjunctiva and urogenital tract, done
      by a direct immunofluorescence assay, McCoy cell culture, and polymerase chain
      reaction. Additionally, antichlamydial immunoglobulin A (IgA) and immunoglobulin
      G (IgG) were determined in sera and tears of all patients by an immunoperoxidase
      assay. RESULTS: Two hundred twelve patients were examined--167 with
      conjunctivitis, 45 with symptoms of urogenital chlamydial infection. Cell
      culture, direct immunofluorescence assay, and polymerase chain reaction brought
      identical results. Conjunctival specimens taken from 33 (20%) of the patients
      with conjunctivitis were Chlamydia antigen positive; specimens taken from 134
      (80%) were negative. Antichlamydial antibodies were found in tears of 29 (88%) of
      the patients with conjunctivitis whose specimens were Chlamydia antigen positive.
      Fifty-four (40%) of the patients with conjunctivitis whose specimens were
      Chlamydia antigen negative had antichlamydial antibodies in their tears. Twenty
      five patients with urethritis (56%) were Chlamydia antigen positive in urethral
      swabs; 20 (44%) were negative. Antichlamydial antibodies were found in the tears
      of eight (32%) of the Chlamydia antigen-positive and two (10%) of the Chlamydia
      antigen-negative patients with urethritis. In contrast to patients with
      conjunctivitis, findings for patients with urethritis always were negative for
      antichlamydial IgG in the tears. CONCLUSION: Antichlamydial antibodies in tears
      were seen significantly more often in patients with conjunctivitis than in those
      with urethritis (P < or = 0.05). Antichlamydial IgG was found only in tears of
      patients with conjunctivitis. Therefore, the authors conclude that the detection
      of antichlamydial IgG in the tears might be helpful for diagnosis in patients
      with suspected chlamydial conjunctivitis who have antigen-negative conjunctival
      swabs.

PMID- 9022117
TI  - Brimonidine tartrate: a one-month dose response study.
AB  - BACKGROUND: Brimonidine tartrate is a relatively selective alpha2-agonist that
      effectively reduces mean intraocular pressure (IOP) and the incidence of IOP
      spikes after laser trabeculoplasty. The authors were interested in evaluating the
      dose response of brimonidine when applied topically for a longer duration in
      patients with elevated IOPs. METHODS: The authors conducted a 1-month,
      multicentered, double-masked, randomized, placebo-controlled, parallel clinical
      study in 194 patients with ocular hypertension or glaucoma (mean IOP, 25.6 +/-
      3.2 mmHg). The authors administered three concentrations of brimonidine (0.08%,
      0.2%, and 0.5%) or placebo bilaterally every 12 hours for 1 month. The authors
      evaluated the following parameters: IOP, heart rate, blood pressure, visual
      acuity, pupil size, basal tear secretion as well as patient comfort at baseline,
      day 1, week 1, week 3, and week 4. RESULTS: All concentrations of brimonidine
      significantly reduced IOP, compared to baseline and placebo, at all follow-up
      visits. Maximum mean IOP decreases from baseline of 20.8%, 27.2%, and 30.1% were
      observed for the 0.08%, 0.20%, and 0.5% treatment groups, respectively. On days 1
      and 21, the 0.2% and 0.5% treatment groups exhibited significantly greater IOP
      decreases than did the 0.08% group. After the initial steep decline in IOP, the
      effect decreased slightly and stabilized at day 14 at the level that was
      maintained throughout the study. The most frequent side effects reported were
      fatigue and dry mouth. No significant changes in heart rate were reported.
      Statistically significant decreases in mean blood pressure without clinical
      symptoms were observed within the 0.2% and 0.5% treatment groups. CONCLUSION:
      Brimonidine 0.2% is well tolerated, efficacious, and shows potential as an agent
      in the long-term treatment of elevated IOP.

PMID- 9022119
TI  - Intermediate-term outcome of variable dose mitomycin C filtering surgery.
AB  - PURPOSE: Trabeculectomy with adjunctive mitomycin C is associated with high
      success rates in studies with follow-up of less than 1 year. This report
      evaluates the visual and intraocular pressure (IOP) outcome in eyes after
      trabeculectomy with adjunctive mitomycin C 1 to 3 years after surgery in a
      predominantly white group (98.1%). METHODS: The records of 157 eyes of 157
      consecutive patients, aged 18 or older, who underwent mitomycin C
      trabeculectomies for uncontrolled glaucoma of various causes were reviewed. All
      surgeries were performed between April 1991 and June 1993. The concentration of
      mitomycin C varied from 0.2 to 0.5 mg/ml and was applied for 30 seconds to 5
      minutes (only one patient received 0.2 mg/ml). Of the 157 eyes, 110 eyes were at
      high risk for failure (previous surgeries or inflammatory glaucoma). Thirty-nine
      eyes had preoperative IOP < or = 21 mmHg. RESULTS: The mean preoperative IOP was
      29.4 +/- 10.3 mmHg. This was reduced to 13.0 +/- 7.6 mmHg at 1 year, 11.5 +/- 6.4
      mmHg at 2 years, and 13.4 +/- 7.3 mmHg at 3 years. Cumulative survival rate by
      life-table analysis was 94.2% +/- 1.9% at 1 year, 92.1% +/- 2.4% at 2 years, and
      88.7% +/- 4.0% at 3 years, where failure was defined as reoperation for control
      of IOP. Complications included cataract formation-progression (n = 31), hyphema
      (n = 26), choroidal detachment (n = 21), hypotony maculopathy (n = 5), and
      endophthalmitis (n = 2). Vision deteriorated in 29 eyes and improved by 2 or more
      Snellen visual acuity lines in 29 eyes. CONCLUSION: The IOP reduction after
      mitomycin C filtering surgery is sustained in the intermediate-term, 1 to 3
      years, follow-up period.

PMID- 9022118
TI  - A comparison of dorzolamide and timolol in patients with pseudoexfoliation and
      glaucoma or ocular hypertension.
AB  - PURPOSE: The purpose of the study is to compare the efficacy and safety profile
      of 2.0% dorzolamide (three times daily) and 0.5% timolol (twice daily) for up to
      6 months in patients with glaucoma or ocular hypertension associated with
      pseudoexfoliation. The additive effects of dorzolamide and timolol in patients
      requiring add-on therapy also was evaluated. METHODS: This was a double-masked,
      randomized, parallel comparison study at 15 Scandinavian sites. One hundred
      eighty-four patients with pseudoexfoliation and either glaucoma or ocular
      hypertension who were 21 to 85 years of age were studied. The treatment groups
      were 2.0% dorzolamide three times daily and 0.5% timolol maleate twice daily.
      RESULTS: At 6 months, the mean percent reduction in intraocular pressure of 2%
      dorzolamide and 0.5% timolol was 24% and 29%, respectively, at morning peak and
      21% and 23%, respectively, at afternoon trough. The additional intraocular
      pressure-lowering effect of adding 2.0% dorzolamide twice daily to patients
      receiving timolol was 14% and 15%, at peak and trough, respectively. There were
      no differences between treatment groups in the incidence of clinical adverse
      experiences, and dorzolamide was not associated with the systemic adverse effects
      typically ascribed to the use of oral carbonic anhydrase inhibitors. CONCLUSION:
      Two percent dorzolamide (three times daily) was effective and well tolerated in
      patients with glaucoma or ocular hypertension associated with pseudoexfoliation
      over the course of 6 months; 0.5% timolol (twice daily) had a greater level of
      intraocular pressure-lowering activity than did dorzolamide, although the
      difference between the two treatments became less pronounced during the study
      period. Finally, 2.0% dorzolamide (twice daily) produced additional lowering of
      intraocular pressure when given with 0.5% timolol (twice daily).

PMID- 9022120
TI  - Glaucoma in phakomatosis pigmentovascularis.
AB  - BACKGROUND: Sturge-Weber syndrome, Klippel-Trenaunay-Weber syndrome, and
      oculodermal melanocytosis are neural crest disorders in which glaucoma is known
      to occur. Phakomatosis pigmentovascularis is a neural crest disorder that is
      found almost exclusively in Asians and has not been described previously in the
      ophthalmic literature. METHODS: The authors describe nine patients with combined
      oculodermal vascular malformations (five pigmentovascularis, two Klippel
      Trenaunay-Weber, two Sturge-Weber) and oculodermal melanocytosis. RESULTS: Ocular
      melanocytosis was present bilaterally in seven patients and unilaterally in two.
      Of the 16 hyperpigmented eyes, 13 also had episcleral vascular malformations
      (EVM). Congenital glaucoma developed in all 10 eyes that had total melanocytosis
      and EVM. Ocular hypertension developed in one eye with diffuse melanocytosis but
      partial EVM in childhood. Glaucoma did not develop in one eye with extensive EVM
      but partial melanocytosis or in the four eyes with ocular melanocytosis but not
      EVM. CONCLUSION: When oculodermal melanocytosis and nevus flammeus (phakomatosis
      pigmentovascularis) occur together, with each extensively involving the globe,
      there is a strong predisposition for congenital glaucoma. When one or both are
      present with only partial involvement, elevated intraocular pressure may develop
      later in life, and patients should be followed-up at regular intervals for the
      development of glaucoma. The vascular malformations appear to play a more
      important role in the predisposition to glaucoma than does the oculodermal
      melanocytosis.

PMID- 9022121
TI  - Early stage human colorectal cancer: prognostic value of nm23-H1 protein
      overexpression.
AB  - Nm23 gene codifies for a nucleoside diphosphate kinase allowing the intracellular
      transduction of the signals. In colorectal cancer nm23 protein expression seems
      related to the progression of the disease. By immunohistochemistry we have
      studied the intracytoplasmatic nm23 H1 protein expression in 20 patients affected
      by colorectal cancer at initial stage. In 12 cases it resulted elevated and in
      four the disease recurred. The overexpression was not correlated with other
      prognostic factors. Nm23 H1-positive patients affected by colorectal cancer at
      initial stage could be considered at risk for disease recurrence and included in
      a more frequent follow-up protocol.

PMID- 9022122
TI  - Effects of oleanolic acid and ursolic acid on inhibiting tumor growth and
      enhancing the recovery of hematopoietic system postirradiation in mice.
AB  - Two triterpene acids, oleanolic acid (OA) and ursolic acid (UA) were examined for
      their ability to inhibit the tumor growth and modify hematopoiesis after
      irradiation in three experimental systems: (a) in vivo anti-tumor activity of
      implanted tumor by ascitic cells was found to be augmented by addition of OA and
      UA at a high concentration and inhibited in a dose-dependent manner; (b) in the
      sublethal whole-body irradiated mice treated with the drugs in the 30 min
      preirradiation period, enhanced effects of OA and UA on peripheral leukocytes
      were observed by a different significance, and (c) when these chemicals were
      administered i.p. to mice 30 min before 4 Gy irradiation, both OA and UA enhanced
      the postirradiation responses of splenic blastogenesis by PHA. UA was a more
      potent tumorigenic inhibitor than OA. Combining with the gamma-irradiation,
      however, there was no significant synergetic effect on their anti-tumor activity.
      The beneficial effects of OA and UA on hematopoiesis and immunocompetence under
      this study, suggested they might partially play a role in anti-cancer and,
      furthermore, with the ability to decrease undesirable radiation damage to the
      hematopoietic tissue after radiotherapy.

PMID- 9022123
TI  - Enhancing effects of captafol on the development of GST-P-positive liver cell
      foci in a medium-term bioassay, and protection by L-cysteine of the enhancement
      in rats.
AB  - The modifying effects of captafol and protective effects of L-cysteine on the
      development of glutathione S-transferase placental form-positive (GST-P +) foci
      of the liver and expression of proliferating cell nuclear antigen (PCNA) in the
      kidney were investigated in a medium-term bioassay using D-galactosamine (DGA) in
      rats. Male 6-week-old F344 rats were initially given a single i.p. injection (200
      mg/kg) of diethylnitrosamine (DEN) and after 2 weeks on basal diet, received two
      i.p. injections of DGA (300 mg/kg) at the ends of weeks 2 and 5, and were fed a
      diet supplemented with test chemicals for weeks 3-8. Animals in group 1 were
      given 1500 ppm captafol in the diet, while group 2 received 1500 ppm captafol in
      diet as well as 1500 ppm L-cysteine in drinking water, animals in control group
      being given basal diet alone. Positive results regarding increased numbers and
      areas of GST-P + liver cell foci were obtained in rats treated with captafol
      alone. On the other hand, significant reduction by L-cysteine in the areas of GST
      P + liver cell foci initiated by DEN and promoted by captafol was observed. In
      addition, the PCNA-labelling indices of renal tubule cells were elevated in rats
      treated with captafol alone and significantly reduced in rats treated
      simultaneously with L-cysteine. The protocol used in the present study therefore
      allowed the in vivo determination of promoting effects of captafol and inhibitory
      influence of L-cysteine by analyzing GST-P + foci in the livers as marker
      lesions, within a relatively short period of 8 weeks. Thus, this bioassay
      protocol could have applicability as a new in vivo assay system for the screening
      of hepatic carcinogenic or anti-carcinogenic agents.

PMID- 9022124
TI  - Expression of basic fibroblast growth factor and its mRNA in advanced uterine
      cervical cancers.
AB  - To know the potential of growth, invasion and metastasis of uterine cervical
      cancer cells associated with neovascularization, the expression of basic
      fibroblast growth factor (FGF) and its mRNA in uterine cervical cancers and
      normal uterine cervices as controls were determined by enzyme-linked
      immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction
      Southern blot (RT-PCR-SB), respectively. Then, the relations between the
      expression and the histological grading and clinical staging in cervical cancers
      were analyzed. The levels of basic FGF and its mRNA were significantly higher in
      advanced primary uterine cervical cancers, regardless of histological type.
      Therefore, this status might contribute to the acceleration of growth, invasion,
      and metastasis with neovascularization in advanced uterine cervical cancers.

PMID- 9022125
TI  - Molecular mechanisms regulating TNF-alpha production by tumor-associated
      macrophages.
AB  - The molecular mechanisms that regulate the production and/or functional activity
      of intratumoral tumor necrosis factor-alpha (TNF-alpha) remain poorly defined. To
      begin to address this issue we have examined the level of TNF-alpha mRNA and
      protein produced by macrophages present within immunogenic Fsa-R and non
      immunogenic Fsa-N tumors grown in syngeneic Lps(d) C3H/HeJ and Lps(n) C3H/HeN
      mice. The results obtained indicate that macrophages isolated from tumors grown
      in Lps(d) C3H/HeJ mice express 5-10-fold less TNF-alpha than equivalent cells
      present in tumors grown in Lps(n) C3H/HeN mice. These data suggest that the
      mechanisms that operate within the tumor microenvironment to induce the
      production of TNF-alpha act, at least in part, via the same signal transduction
      pathway that is defective in Lps(d) C3H/HeJ mice. Interestingly, despite such
      differences in TNF-alpha production, tumors inoculated into C3H/HeJ and C3H/HeN
      mice grew at a similar rate and contained an almost identical proportion of
      macrophages. Moreover, tumor cells purified from tumors grown in C3H/HeJ and
      C3H/HeN mice produced similar quantities of the TNF-alpha-inducible cytokine GM
      CSF. Thus, although differences in the level of TNF-alpha produced within tumors
      grown in C3H/HeN and C3H/HeJ mice are readily demonstrable, such differences
      appear to have little direct impact on the outcome of tumor growth.

PMID- 9022126
TI  - Kinetics of arylamine N-acetyltransferase in tissues from human breast cancer.
AB  - N-Acetyltransferase activity and Michaelis-Menten kinetic constants were
      determined in cancerous and non-cancerous breast tissues from 30 female patients
      with breast cancer. The results derived from tissue cytosol showed that 12 rapid,
      ten intermediate and eight slow acetylators based on p-aminobenzoic acid and 2
      aminofluorene for substrates. The mean apparent Km values for the monomorphic
      substrate p-aminobenzoic acid and polymorphic substrate 2-aminofluorene were:
      55.0 +/- 18.7, 114.0 +/- 30.0, and 137.0 +/- 37.2 microM; and 62.5 +/- 23.7,
      166.0 +/- 67.0, and 239.0 +/- 76.6 microM for the slow, intermediate, and rapid
      enzymes, respectively. Compared to the enzymes from slow acetylators, the rapid
      acetylators exhibited mean apparent Vmax values eight- and ten-fold greater for p
      aminobenzoic acid and 2-aminofluorene, respectively. A similar trend was obtained
      from the blood cytosols of cancerous patients and healthy volunteers. N
      Acetyltransferase activity of breast cancerous and non-cancerous tissues were 1.5
      and 2.2-fold different between rapid and slow acetylator with p-aminobenzoic
      acid and 2-aminofluorene as substrates, respectively. In breast cancerous
      tissues, 75% and 70% of the cytosolic N-acetyltransferase activity were inhibited
      under 2 mM of tamoxifen as substrates of 2-aminofluorene and p-aminobenzoic acid,
      respectively. Similar results were also found in non-cancerous tissues and blood
      samples from breast cancer patients and healthy volunteers. The effect of 1 mM
      tamoxifen on the N-acetyltransferase activity from breast cancerous tissues with
      positive estrogen receptor was 1.6-fold higher than that of negative estrogen
      receptor. This is the first demonstration to show that anti-estrogen drug can
      affect N-acetyltransferase activity in breast cancerous tissues. Therefore, this
      finding may provide a clue to the use of tamoxifen in prevention of human breast
      cancer.

PMID- 9022127
TI  - Human squamous carcinoma cell invasion in organ-cultured skin.
AB  - In a previous study we showed that normal human epidermal keratinocytes were
      capable of invading the dermis of organ cultured skin when the tissue was treated
      with an exogenous source of epithelial growth factors (Fligiel and Varani (1993)
      Invasion Metastasis, 13, 225-233). Here we examined human squamous carcinoma
      cells from three different tumors for ability to invade the dermis in the same
      model. Invasion occurred in 40-80% of the tissues, depending on the tumor line,
      and was observed with equal frequency under both growth factor-free conditions
      and in the presence of exogenous growth factors. These data demonstrate that
      malignant human epithelial cells have the capacity to invade the dermis of organ
      cultured skin. Unlike normal keratinocytes, there appears to be no exogenous
      growth factor requirement for invasion by the malignant cells.

PMID- 9022128
TI  - Combination of melatonin and tamoxifen as a chemoprophylaxis against N-nitroso-N
      methylurea-induced rat mammary tumors.
AB  - The effect of melatonin (Mel) and or tamoxifen (Tam) was evaluated on a mammary
      tumor model induced in 50 day old female Sprague-Dawley rats by a single
      intraperitoneal (i.p.) injection of a direct carcinogen, N-nitroso-N-methylurea
      (NMU) (50 mg/kg b.wt./rat). These animals were treated with either Mel 200
      microg/rat per day, orally in drinking water and/or Tam (s.c.) 60 microg/rat per
      week or 180 microg/rat per week. The total observation period was 300 days post
      NMU administration in all the animals. The mean latency period of tumor
      appearance and tumor incidence was recorded. The mean latency period was
      significantly lengthened in all the treated groups as compared to that in the
      only NMU-administered rats (P < 0.001). Highly significant suppression of tumor
      incidence was observed in Mel + Tam180 group (P < 0.001). The other two groups
      i.e. Mel + Tam60, and Tam180 also showed significant suppression of tumor
      incidence (P < 0.01). Eight weeks after the initiation of treatment regimen, we
      observed marked reduction in [3H]thymidine incorporation into mammary gland DNA
      of Mel- and/or Tam-treated groups of animals as compared to the age-matched
      controls and NMU-administered rats, which correlated positively with the sparse
      mammary gland development seen in the whole mount preparations. The result of the
      combined therapy is highly promising and warrants clinical evaluation in the
      prophylaxis of breast carcinogenesis in humans.

PMID- 9022129
TI  - Cripto expression in human urological tumors.
AB  - The expression of cripto, a novel transforming gene of the epidermal growth
      factor superfamily, was immunohistochemically examined in 20 cases of urinary
      bladder, one ureter, three renal pelvic, 18 kidney, nine prostate, three adrenal
      and four testicular tumors. Three cases of urinary bladder carcinomas, two of
      grade 2 and one of grade 3 transitional cell carcinoma which were T1a and T3b,
      and INF beta and INF gamma, respectively, showed positive binding of specific
      antibody, along with one cortical carcinoma of the adrenal gland positive
      staining. None of the ureter, renal pelvic, kidney, prostate or testicular tumors
      showed positive staining. These results indicate that cripto is not frequently
      expressed in urological tumors.

PMID- 9022130
TI  - Molecular analysis of the secretory phospholipase A2 gene, a candidate of Mom1
      gene, in neuroblastomas.
AB  - Mice with hereditary intestinal polyposis have mutations of the APC gene which
      causes formation of multiple polyps. At least one other gene influences the
      susceptibility for development of polyps in mice, and the locus was named Mom1.
      The causative gene for the Mom1 locus has recently been cloned and was found to
      be identical to the secretory type II phospholipase A2 (PLA2S-II) gene. Although
      the mechanism of contribution of PLA2S-II to formation of polyps is unclear,
      abnormalities of the PLA2S-II gene contribute to cellular transformation in mice.
      We speculated that this gene could contribute to tumorigenesis in human
      neoplasms. The human homologue of this gene maps to 1p35-36.1. Chromosomal
      deletions involving this region are frequently observed in neuroblastomas. We
      analyzed 19 neuroblastomas to detect point mutations of the PLA2S-II gene by PCR
      single strand conformational polymorphism (SSCP). A polymorphism was detected at
      codon 32; no point mutations were found in the coding region of the gene.
      Moreover, in cases that were heterozygous at codon 32, three samples had
      hemizygous deletion of the gene. Taken together, PLA2S-II is frequently
      hemizygously deleted, but no point mutations are observed in neuroblastomas.

PMID- 9022131
TI  - Effects of administered route on tissue distribution and antitumor activity of
      polyethyleneglycol-coated liposomes containing adriamycin.
AB  - Tissue distribution, antitumor activity and side effects after intraperitoneal
      administration of polyethyleneglycol-coated liposomes containing adriamycin (PEG
      LADR) were examined and compared to that after intravenous treatment. Plain
      liposomes (PLADR) and PEG-LADR appeared to maintain blood circulation by
      intraperitoneal injection and suggested usefulness in passive targeting. Because
      of the accumulation of ADR in the pancreas found after intraperitoneal treatment,
      this administered route of PLADR and PEG-LADR was expected to be useful as a
      method of targeting the pancreas. The side effects of ADR in the heart and liver
      were suppressed by the liposomalization and PEG-modification. The antitumor
      effect of ADR was increased by the liposomalization, and PEG-modification after
      intraperitoneal administration was superior to that after intravenous
      administration. The slowly disappearing pattern of PLADR and PEG-LADR from the
      abdominal cavity was similar. It is suggested that PLADR and PEG-LADR were
      absorbed intact from the abdominal cavity and transferred into the blood
      circulation.

PMID- 9022132
TI  - Protein phosphatase-2A association with microtubules and its role in restricting
      the invasiveness of human head and neck squamous cell carcinoma cells.
AB  - The role of protein phosphatase-2A (PP-2A) in regulating the motility and
      adhesion of human head and neck squamous cell carcinomas (HNSCC) was
      investigated. Immunofluorescent staining of these HNSCC cells showed PP-2A can co
      localize with microtubules. That the PP-2A influences motility was shown by the
      increase in HNSCC cell migration through laminin and vitronectin when PP-2A was
      selectively inhibited with low dose okadaic acid, and by the reduction in
      invasion through these same matrix components by elevators of PP-2A activity.
      Motility of HNSCC cells through collagen I or fibronectin was not modulated by PP
      2A. The reduction in HNSCC migration through vitronectin or laminin that resulted
      from treatment with PP-2A elevators was associated with an increase in cellular
      adhesiveness to these same ECM components. These studies show the association of
      PP-2A with the cellular cytoskeleton and its role in restricting the invasiveness
      of tumor cells through select extracellular matrix components.

PMID- 9022133
TI  - Induction of invasive squamous cell carcinomas in the forestomach of (C3H x
      MSM)F1, MSM, and C3H mice by N-methyl-N-nitrosourea and mutational analysis of
      the H-ras and p53 genes.
AB  - Genetic analysis of tumors developing in F1 hybrids between genetically separate
      strains of mice makes it possible to search for loss of heterozygosity (LOH),
      information on which provides clues to finding tumor-suppressor genes. For this
      purpose, however, reproducible carcinogenic conditions for the organ of interest
      need to be first determined. In the present study, a forestomach model of
      squamous cell carcinomas (SCCs), induced in (C3H x MSM)F1 mice by N-methyl-N
      nitrosourea (MNU), was established and mutational changes in the H-ras and p53
      genes were examined in tumors. Male (C3H x MSM)F1, MSM and C3H mice were given
      MNU by i.g. intubation once a week at a dose of 0.03 mg/g body weight for 10
      weeks, then kept without further treatment. At experimental weeks 38-46, markedly
      invasive SCCs were observed in the forestomach at incidences of 9/14 (64.3%),
      9/16 (56.3%), and 2/10 (20.0%), respectively. In the three strains of mice, DNA
      analysis of SCCs by PCR-SSCP analysis followed by direct DNA sequencing revealed
      low incidences of point mutations in the H-ras (4/20, 20%) and p53 (3/20, 15%)
      genes. The results demonstrate the usefulness of the present animal experimental
      protocol for induction of high grade SCC in the forestomach of (C3H x MSM)F1
      mice, and suggest the possibility that point mutations in the H-ras or p53 genes
      may play some role in pathways leading to the development of such lesions.

PMID- 9022134
TI  - Induction of aberrant crypt foci in C57BL/6N mice by 2-amino-9H-pyrido[2,3
      b]indole (A alphaC) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx).
AB  - The inductions of aberrant crypt foci (ACF) by two carcinogenic heterocyclic
      amines (HCAs), 2-amino-9H-pyrido[2,3-b]indole (A alphaC) and 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx), were studied in the large intestine of
      C57BL/6N mice. Seven-week-old mice were fed a diet supplemented with 500 or 800
      ppm of A alphaC, or 400 or 600 ppm of MeIQx for 7 weeks, followed by a basal diet
      for another 7 weeks. A alphaC at 800 ppm induced 8.0 +/- 1.9 and 7.8 +/- 2.5 ACF
      in female and male mice, respectively. MeIQx at 600 ppm induced 2.8 +/- 1.8 and
      1.6 +/- 0.8 ACF in females and males, respectively. At lower concentrations of A
      alphaC and MeIQx, many fewer ACF were induced. No ACF were induced in the control
      group. The size of ACF (number of aberrant crypts/ACF) in all experimental groups
      was between 1.0 and 1.5. More than half the A alphaC-induced ACF were located in
      the region about 20-40% of the distance from the ileocecal portion to the anus.
      Although both of these HCAs were reported to induce tumors in the liver and other
      organs, but not in the large intestine, of CDF1 mice, these findings suggest that
      both these HCAs, and especially A alphaC, induce large intestinal tumors in
      C57BL/6N mice.

PMID- 9022135
TI  - Tumor growth, weight loss and cytokines in SCID mice.
AB  - It has been proposed that immunoregulatory cytokines play a role in the onset and
      development of cancer cachexia, although evidence supporting this theory remains
      inconclusive. In the present study, SCID mice were implanted with one of two
      tumor cell lines known to induce weight loss in rats. Growth of the Morris 7777
      hepatoma was associated with weight loss as well as increased levels of tumor
      necrosis factor and interleukins 1 and 6 in spleen cells of tumor-bearing mice.
      Growth of the MCA sarcoma did not induce weight loss, nor did it increase
      cytokine expression in spleen cells of tumor-bearing mice. We conclude that
      increased cytokine expression is associated with weight loss in tumor-bearing
      SCID mice, and immune activation for cytokine expression does not require the
      presence of T or B cells.

PMID- 9022137
TI  - Investigation of c-myc and K-ras amplification in renal clear cell
      adenocarcinoma.
AB  - Tumour DNA samples isolated from 36 patients with renal clear cell carcinoma were
      investigated for c-myc and K-ras amplification, using a quantitative dot-blot
      hybridization. The characteristic clinical and histological parameters involved
      in the statistical analysis were age, sex, histological grade of the tumour, the
      TNM staging system, tumour size and weight, vascular invasion and the quality of
      life. The goal of the study was to estimate the prevalence as well as the
      prognostic value of the amplification of the oncogenes in question. Amplified c
      myc (2.47-fold on the average) was found in three specimens (8.3%), showing
      slight correlation with intravasation (P > 0.05, n.s.). K-ras amplification (2.93
      fold) detected in six tumours (16.6%) was shown to significantly correlate with
      both histological grade (2.2 vs. 1.8, P < 0.05) and tumour size (15 vs. 8 cm, P <
      0.05). In cases with amplified K-ras also lymph node involvement was somewhat
      more frequent (P > 0.05, n.s.). No coamplification of these oncogenes was
      observed. The results of the study suggest that K-ras amplification may account
      for a more rapid progression of the disease.

PMID- 9022136
TI  - Alteration of midkine expression associated with chemically-induced
      differentiation in human neuroblastoma cells.
AB  - Midkine (MK), a neurotrophic polypeptide of which expression is developmentally
      regulated in embryogenesis, is expressed in malignant tumor tissues including
      neuroblastoma (NB). A retinoic acid analogue, E5166, and dibutyryl cyclic AMP
      (dbcAMP) are known to induce differentiation in NB cells. This study showed that
      MK mRNA expression increased in association with differentiation by E5166, but
      not by dbcAMP in SK-N-SH and KP-N-RTBM1 human NB cell lines. We concluded that MK
      could be an important factor in differentiation of NB cells, and further, that
      there could be at least two pathways in differentiation of NB cells at molecular
      mechanism.

PMID- 9022138
TI  - Growth inhibition of MCF-7 and MCF-10A human breast cells by alpha-tocopheryl
      hemisuccinate, cholesteryl hemisuccinate and their ether analogs.
AB  - The growth inhibitory properties of alpha-tocopheryl hemisuccinate (vitamin E
      succinate) and related compounds were examined in MCF-7 human breast tumor cells
      and MCF-10A normal-like human breast cells since they have been suggested to be
      an effective antitumor compound. The data showed that both alpha-tocopherol
      hemisuccinate and a structurally-similar compound, cholesteryl hemisuccinate,
      inhibited the growth of MCF-7 and MCF-10A cells, while alpha-tocopherol,
      cholesterol, cholesteryl sulfate and Tris succinate had little effect on cell
      growth. The ether analogs of the succinate esters, alpha-tocopheryloxybutyric
      acid and cholesteryloxybutyric acid, also inhibited growth of MCF-7 and MCF-10A
      cells, indicating that hydrolysis of the succinate esters by esterases is not
      required for the antiproliferative effects. The antiproliferative effects of
      these succinate esters and ethers may be related to their physiochemical
      properties that allow incorporation into cell membranes.

PMID- 9022140
TI  - Carcinogen-induced alteration in liver epidermal growth factor receptor
      distribution during the promotion stage of hepatocarcinogenesis in rat.
AB  - Changes in hepatic membrane binding capacity for epidermal growth factor (EGF)
      were assessed during 2-acetylaminofluorine (2-AAF)-induced hepatocarcinogenesis.
      An overall decrease in membrane EGF binding levels was observed throughout the
      period of 2-AAF administration. Immunochemical studies indicated the decreases in
      EGF binding levels were paralleled by decreases in tissue EGF receptor levels.
      Immunohistochemical studies showed that the losses in hepatic EGF receptor levels
      were not uniform throughout the liver during the early, promotion stage of cancer
      development. During the promotion stage, preneoplastic liver nodules were found
      to display a higher level of EGF receptor than surrounding hepatic tissue. This
      resistance to 2-AAF-mediated down-regulation of EGF receptor may confer a
      proliferative advantage to the developing nodule relative to the surrounding
      liver tissue. Similar immunochemical and immunohistochemical analysis of
      hepatocarcinomas at late stages of 2-AAF-induced hepatocarcinogenesis indicated a
      uniform loss of EGF receptor in tumor and surrounding tissue. These studies
      indicate that carcinogen-mediated changes in EGF binding levels are different
      during the multistage process of hepatocarcinogenesis, and that resistance to
      down-regulation of EGF receptor among preneoplastic nodules may have a role in
      providing a selective growth advantage to initiated cell populations. EGF
      receptor may be useful as a dynamic marker assessing the development of hepatic
      tumors.

PMID- 9022139
TI  - Prevention of mammary preneoplastic transformation by naturally-occurring tumor
      inhibitors.
AB  - Aberrant hyperproliferation (AH) is a late occurring post-initiational event that
      precedes mammary tumorigenesis in vivo. Experiments on the spontaneously
      immortalized, non-tumorigenic murine mammary epithelial C57/MG and MMEC cells
      were designed to validate AH as an in vitro cellular marker for preneoplastic
      transformation. Colony forming efficiency (% CFE) in anchorage-independent
      conditions of growth represented the quantitative parameter for AH. C57/MG and
      MMEC cells, upon treatment with chemical carcinogens or transfection with
      oncogenes, exhibited at least a 60-300-fold increase in AH relative to that seen
      in appropriate untreated controls. Transplantation of mammary epithelial cells
      initiated either by chemical carcinogens or by oncogenes into mammary fat pads of
      syngeneic mice produced rapidly growing tumors at the transplant site within 4-6
      weeks. The tumor-derived T1/Pr1 and myc3/Pr1 cell lines (positive controls)
      exhibited at least an 800-900-fold increase in AH. Treatment of initiated cells
      with naturally occurring tumor inhibitors eicosapentaenoic acid (EPA), indole-3
      carbinol (I3C), (-)epigallocatechin gallate (EGCG), squalene (SQE), and perillyl
      alcohol (PA) at non-toxic doses, resulted in a 70-99% inhibition of AH, depending
      on the initiator and the chemopreventive test compound. Upregulation of AH in
      initiated mammary epithelial cells in vitro prior to tumorigenesis in vivo, and
      persistent inhibition of AH by diverse naturally occurring tumor inhibitors,
      provides evidence for AH as a cellular surrogate endpoint for induction and
      modulation of mammary neoplastic transformation.

PMID- 9022141
TI  - Tumour vessel damage resulting from laser-induced hyperthermia alone and in
      combination with photodynamic therapy.
AB  - This study examined tumour vessel injury resulting from laser-induced
      hyperthermia alone and in combination with photodynamic therapy (PDT) in the
      treatment of rat liver tumours by means of scanning electron microscopy. A total
      of 18 Wistar rats were divided into three groups. Group I (six animals) underwent
      hyperthermia for 15 min (15-min hyperthermia). Group II (six animals) underwent
      hyperthermia for 30 min (30-min hyperthermia). Group III (six animals) received
      the combined treatment of PDT and 30-min hyperthermia. For PDT, delta-amino
      laevulinic acid at a dose of 60 mg/kg of body weight was intravenously
      administered 60 min before irradiation at 635 nm. The morphological results
      indicated that 15-min hyperthermia gave rise to an increase in permeability of
      the vessels in the treated tumour. Thirty-min hyperthermia caused extreme oedema
      of vascular endothelial cells and restrictive openings of tumour branch vessels.
      The combined therapy of PDT and hyperthermia destroyed tumour vasculature. Large
      breaks of the inner wall of the treated tumour vessels were deeply involved in
      the basement membrane of the vessel. The results indicate that there may be a
      close link between inhibition of tumour growth and degree of damage to tumour
      vessels.

PMID- 9022142
TI  - A study of tobacco carcinogenesis, LIII: carcinogenicity of N'-nitrosonornicotine
      (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mink (Mustela
      vison).
AB  - In an earlier study, young male and female mink (Mustela vison) were found to be
      highly susceptible to the carcinogenic effect of N'-nitrosonornicotine (NNN). In
      this follow-up study we tested (i) the importance of the age of the animals with
      regard to the carcinogenic effect of NNN, (ii) the carcinogenic activity of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and (iii) the combined
      carcinogenic effect of NNN plus NNK. (I) In the previous study, the latency of
      nasal tumor induction by NNN (11.9 mM) averaged 84 +/- 40 weeks upon twice weekly
      applications, starting at the age of 3 weeks and continuing for 38 weeks. In this
      bioassay, giving NNN in 28 weeks but starting at the age of 3 months, it took, on
      the average, 97 +/- 29 weeks to induce malignant nasal tumors, primarily
      esthesioneuroepithelioma with invasion of the brain. (ii) NNK (6.3 mM), given by
      s.c. injection, induced nasal carcinoma with invasion of the forebrain after 77
      +/- 39 weeks. (iii) NNN (11.9 mM) plus NNK (6.3 mM) led to the same type of
      carcinoma but at an accelerated pace, namely after 71 +/- 57 weeks. This study
      supports the earlier observation that tobacco-specific N-nitrosamines induce
      malignant tumors of the nasal cavity with invasion of the brain, dependent to
      some degree on the age of the mink at first application. NNK appears to be a
      stronger carcinogen than NNN in mink which follows the observations made with
      mice, rats and hamsters. It is suggested that combined administration of NNN with
      NNK induces a stronger carcinogenic effect than NNN or NNK given alone.

PMID- 9022143
TI  - P53 gene mutations in osteosarcomas in the dog.
AB  - Osteosarcomas in 18 dogs were examined for the presence of p53 mutations in exons
      4-8 by single strand conformation polymorphism (SSCP) analysis, followed by
      sequence analysis in tumors demonstrating abnormal bands in the SSCP analysis.
      P53 mutations were found in four of the primary tumors in 17 dogs. Metastases
      studied in two of these dogs in which the primary tumor contained only wild type
      p53 did not contain mutations, nor those of one dog in which the primary tumor
      was not studied. The alterations that were found included three missense
      mutations and one 3 bp insertion.

PMID- 9022144
TI  - Subcutaneous, omentum and tumor fatty acid composition, and serum insulin status
      in patients with benign or cancerous ovarian or endometrial tumors. Do tumors
      preferentially utilize polyunsaturated fatty acids?
AB  - The relationships between the fatty acid composition of cancerous endometrium and
      ovary, and peripheral adipose tissues were studied in Israeli Jewish women, and
      are presented together since no differences were shown between them. The results
      suggest a mobilization of linoleic acid from subcutaneous and omental depots and
      its incorporation into tumors accompanied by a high degree of desaturation. High
      blood insulin concentrations characterized patients with stage I and II disease,
      and low concentrations characterized patients with advanced degrees of
      malignancy.

PMID- 9022145
TI  - Induction of peroxisomal enzymes in rat liver by dehydroepiandrosterone sulfate.
AB  - Male F-344 rats, when treated with either 150 mg/kg or 300 mg/kg body weight of
      DHEAS for 14 days, produced a dose-dependent increase in liver weight and
      peroxisomal beta-oxidation activity, characteristic of peroxisomal proliferation.
      Contrary to previous observations in vitro, we also found a significant increase
      in catalase activity in rat liver with the higher dose of the steroid.
      Furthermore, the in vivo induction of peroxisomal beta-oxidation by DHEAS
      observed in our study was significantly less than reported in vitro, and also
      unlike previously reported in vitro results, was approximately equivalent to DHEA
      administered in vivo.

PMID- 9022146
TI  - Decreased expression and rare somatic mutation of the CIP1/WAF1 gene in human
      hepatocellular carcinoma.
AB  - CIP1/WAF1, a critical downstream effector of tumor suppressor p53, encodes a
      cyclin-dependent kinase inhibitor. By Northern blot analysis, the CIP1/WAF1 mRNA
      level in the tumor was significantly lower than that in the corresponding normal
      liver from 19 Japanese patients with hepatocellular carcinoma (P < 0.05). In the
      tumor from only one out of 19 patients (5%), somatic mutations of the CIP1/WAF1
      as well as that of p53 gene were identified by RT-PCR/SSCP analysis. These
      results suggest that the decreased CIP1/WAF1 expression is involved in the
      carcinogenesis or the progression of hepatocellular carcinoma.

PMID- 9022147
TI  - Expression of alpha2-macroglobulin receptor/low density lipoprotein receptor
      related protein on surfaces of tumour cells: a study using flow cytometry.
AB  - alpha2-Macroglobulin receptor/low density lipoprotein receptor-related protein
      (alpha2 MR/LRP) is a multifunctional cell surface receptor that binds and
      endocytoses several structurally and functionally distinct ligands. Very little
      is known about the expression and function of alpha2 MR/LRP in tumour cells. The
      aim of this study was to quantify the number of alpha2 MR/LRP on surfaces of
      human tumour cells by flow cytometry. Using human alpha2 MR/LRP monoclonal
      antibody 8G1, human peripheral blood lymphocytes (negative control cells),
      monocytes (positive control cells), human neonatal foreskin fibroblast cells
      (NFF) (positive control cells), three human breast cancer cell lines (BT-20, T
      47D, and MCF-7), two human ovarian tumour cell lines (JAM, and CI80-13S), and
      five human melanomas (MM418c1, MM253c1, A2058, MM138, MM370) were indirectly
      labelled with goat anti-mouse IgFITC. The fluorescent signals of stained cells
      were measured by flow cytometry. Using Quantum Simply Cellular bead standards,
      the number of alpha2 MR/LRP binding sites per cell was assessed. The flow
      cytometric method to quantify of alpha2 MR/LRP described here is simple and
      reliable. All the human tumour cell lines so far examined express alpha2 MR/LRP
      at different levels from approximately 300 to approximately 10000 sites per cell.

PMID- 9022148
TI  - Differential response of photosensitized young and old human erythrocytes to
      photodynamic activation.
AB  - It has recently been proposed that photosensitized erythrocytes may play an
      important role in the delivery and targeting of agents such as photosensitizers
      and chemotherapeutics for use in cancer treatment. It has been suggested that
      loading of photosensitized erythrocytes with chemotherapeutic agents would
      provide an ideal means of combining both treatment modalities. The recent
      application of real-time confocal laser scanning microscopy to the study of
      immediate effects of photodynamic activation on photosensitized erythrocytes has
      enabled us, in this study, to distinguish between the differential susceptibility
      of age-density resolved sub-populations of human erythrocytes to photodynamic
      activation. In this study we demonstrate that younger (low age-density) sub
      populations of photosensitized erythrocytes are less susceptible than older (high
      age-density) sub-populations to photodynamic activation. We also demonstrate that
      this phenomenon is exhibited by cells photosensitized using hematoporphyrin
      derivative and rose bengal as photosensitizers. In both cases no significant
      difference in uptake of photosensitizer by both populations could be observed
      using absorbance spectrophotometry. The study suggests that age-density
      resolution of erythrocytes prior to loading and photosensitization might provide
      a means of enhancing the release of loaded components from the photosensitized
      system and this would, in turn, enhance the potential use of photosensitized
      erythrocytes as delivery or targeting systems for use in combination cancer
      therapies.

PMID- 9022149
TI  - Fluorescent diagnosis of experimental gastric cancer using a tumor-localizing
      photosensitizer.
AB  - To clarify the usefulness of fluorescent diagnosis for gastric cancer, we
      assessed the sensitivity and specificity of the tumor-localizing photochlorine
      photosensitizer ATX-S10 in combination with a new fluorescence diagnostic system.
      Into the submucosa of the stomachs of five rabbits, VX-2 tumor cells originating
      from squamous cell carcinoma were injected. After 3 weeks, three rabbits (Group
      I) were sacrificed 3 h after intravenous injection of ATX-S10 at a dose of 20
      mg/kg, and their stomachs were observed by the Hg-lamp-induced fluorescence
      diagnostic system. The other two rabbits (Group II) were also sacrificed without
      injection of ATX-S10 and observed by the same method. In all cases in Groups I
      and II, gastric cancers that were invaded from the submucosa to the serosa were
      recognized histologically. The concentration of ATX-S10 examined by high
      performance liquid chromatography (HPLC) in the gastric cancer was significantly
      higher than in the normal stomach. Fluorescent spectroscopy could detect 630 nm
      fluorescence selectively, consistent with the cancerous tissue of Group I.
      Moreover, fluorescent images were detected in only the exposed area of cancerous
      tissue and were undetected in the surrounding normal mucosa. Conversely, no
      fluorescent images could be detected in the stomachs of Group II. It is suggested
      that a fluorescence diagnostic system using ATX-S10 may become useful for the
      diagnosis of the existence or extension of carcinoma of the gastrointestinal
      tract.

PMID- 9022150
TI  - Enhancement of metastasis of prostate adenocarcinoma cells by immune-suppressive
      cyclosporine A.
AB  - The rate and extent of metastasis by prostate adenocarcinoma-III cells was
      enhanced in Lobund-Wistar rats by administration of immune-suppressive
      cyclosporine A. PA-III cells spread from the subcutaneous PA-III-derived tumor,
      through ipsilateral lymph nodes, to the lungs in which they developed secondary
      tumors. Swollen lymph nodes, compacted with PA-III cells, indicate that the
      'normal' host-engendered level of intravascular non-specific restraints to
      metastasis were abrogated by CSA.

PMID- 9022151
TI  - Adriamycin induces apoptosis in rat thymocytes.
AB  - Apoptosis is a controlled form of cell death accompanied by distinct
      morphological and biochemical changes. In this study the nature of cytotoxicity
      induced by adriamycin (ADM) in rat thymocytes was evaluated. Morphological and
      biochemical changes characteristic of apoptosis were found to precede adriamycin
      induced cell death. Our findings demonstrate the involvement of c-Myc, c-Jun,
      antioxidant enzymes CuZn superoxide dismutase and catalase, and perhaps poly ADP
      ribosylation in ADM-induced cell death.

PMID- 9022152
TI  - The lethal (2) giant larva (l(2)gl), a recessive oncogene, is required during
      embryonic and post-embryonic development in Drosophila.
AB  - Recessive oncogenes have genetic functions important for the regulation of tissue
      growth and differentiation. Defining the role of these genes in normal
      developmental and physiological processes is important to the development of the
      accurate models of the normal regulation of growth and differentiation. We report
      here a genetic analysis of the requirement for the lethal (2) giant larva
      function during development. The results demonstrate that the lethal (2) giant
      larva function is required during embryonic and post-embryonic development to
      maintain the normal developmental capacity.

PMID- 9022153
TI  - Characterization of rabbit DNA microsatellites extracted from the EMBL nucleotide
      sequence database.
AB  - Microsatellite polymorphisms are invaluable for mapping vertebrate genomes. In
      order to estimate the occurrence of microsatellites in the rabbit genome and to
      assess their feasibility as markers in rabbit genetics, a survey on the presence
      of all types of mononucleotide, dinucleotide, trinucleotide and tetranucleotide
      repeats, with a length of about 20 bp or more, was conducted by searching the
      published rabbit DNA sequences in the EMBL nucleotide database (version 323). A
      total of 181 rabbit microsatellites could be extracted from the present database.
      The estimated frequency of microsatellites in the rabbit genome was one
      microsatellite for every 2-3 kb of DNA. Dinucleotide repeats constituted the
      prevailing class of microsatellites, followed by trinucleotide, mononucleotide
      and tetranucleotide repeats, respectively. The average length of the
      microsatellites, as found in the database, was 26, 23, 23 and 22 bp for mono-, di
      , tri- and tetranucleotide repeats, respectively. The most common repeat motif
      was AG, followed by A, AC, AGG and CCG. This group comprised about 70% of all
      extracted rabbit microsatellites. About 61% of the microsatellites were found in
      non-coding regions of genes, whereas 15% resided in (protein) coding regions. A
      significant fraction of rabbit microsatellites (about 22%) was found within
      interspersed repetitive DNA sequences.

PMID- 9022154
TI  - Intra- and interbreed genetic variations of mitochondrial DNA major non-coding
      regions in Japanese native dog breeds (Canis familiaris).
AB  - Mitochondrial DNA (mtDNA) major non-coding regions were amplified from 73 dogs of
      eight Japanese native dog breeds and from 21 dogs of 16 non-Japanese dog breeds
      by the polymerase chain reaction and their DNA sequences were determined. A total
      of 51 nucleotide positions within the non-coding region (969-972 base pairs)
      showed nucleotide variations of which 48 were caused by transition. These
      nucleotide substitutions were abundant in the region proximate to tRNA(Pro). In
      addition to the nucleotide substitutions, the dog mtDNA D-loop sequences had a
      heteroplasmic repetitive sequence (TACACGTAGCG) involving size variation. The DNA
      sequences of the non-coding region were classified into four different groups by
      phylogenetic analysis and the deepest branchpoints of this dog phylogeny was
      calculated to about 100,000 years before the present. Phylogenetic analysis
      showed that Japanese native dog breeds could not be clearly delimited as distinct
      breeds. Many haplotypes found in members of some clustering groups were seen in
      each dog breed, and interbreed nucleotide differences between Japanese dog breeds
      were almost the same as the intrabreed nucleotide diversities.

PMID- 9022155
TI  - The relative abundance of a salivary protein, bSP30, is correlated with
      susceptibility to bloat in cattle herds selected for high or low bloat
      susceptibility.
AB  - Pasture bloat is a serious economic and animal welfare problem in cattle grazed
      on legumes in New Zealand. Analysis of salivary proteins from dairy cattle in
      herds bred for either low or high susceptibility to bloat has resulted in the
      identification of a 30 kilodalton protein, which we term bSP30, whose relative
      abundance is negatively correlated with bloat score (r = -0.40 +/- 0.12). From 74
      animals sampled, relative abundance of bSP30 was 66 +/- 15% higher in the low
      susceptibility herd than in the high-susceptibility herd. Relative abundance of
      bSP30 also varied significantly within individuals, according to feeding or time
      of day, and from day to day. A sequence homology search of 38 amino acids derived
      from three tryptic fragments of the protein suggests that the amino acid sequence
      of bSP30 has not been described previously. Amino acid analysis indicates that
      bSP30 is not a member of the proline-rich family of salivary proteins. The
      function of bSP30 is unknown but it is conceivable that it plays a role in the
      aetiology of bloat.

PMID- 9022156
TI  - Comparison of protein markers and microsatellites in differentiation of cattle
      populations.
AB  - Five cattle populations, representing four breeds, were analysed for 14 protein
      markers and five microsatellite loci. The breeds studied were Brown Swiss and
      three autochthonous Spanish cattle: Avilena-Negra Iberica (A-NI), two populations
      (A-NI 1 and A-NI 2) from different, reproductively isolated, locations;
      Sayaguesa; and Morucha. A total of 752 animals were examined for biochemical
      polymorphisms, of which 488 were also DNA typed. Genetic parameters and
      phylogenetic trees were obtained separately for each group of markers and results
      were compared. Estimates of heterozygosity and genetic distances from
      microsatellites were greater than those obtained using protein markers. The
      overall topology of the two dendrograms was similar. A-NI 1 and A-NI 2
      populations were grouped together, related to Morucha, and the three of them
      related to Sayaguesa. Brown Swiss appeared in a separate branch from Spanish
      cattle. These results support the usefulness of microsatellites in the study of
      genetic relationships among closely related populations and breeds.

PMID- 9022157
TI  - Syntenic assignment of dopamine tautomerase (DCT) to bovine chromosome 12.
AB  - Heterologous primers were used to amplify an exon and intron-containing segment
      of the bovine homologue of the human dopachrome tautomerase gene. After
      confirmation of homology by sequence analysis (exon sequence similarity greater
      than 90%), bovine-specific primers were developed for synteny mapping purposes.
      The dopachrome tautomerase gene was assigned to bovine chromosome 12 (BTA12) with
      97% concordance to the coagulation factor 10 locus. Together with previous
      synteny mapping of bovine chromosome 12 genes, fms-related tyrosine kinase,
      esterase D and 5-hydroxytryptamine receptor 2, this assignment further indicates
      conservation between human chromosome 13q and bovine chromosome 12.

PMID- 9022158
TI  - Optimization of single-strand conformation polymorphism and sequence analysis of
      the mitochondrial control region in Pagellus bogaraveo (Sparidae, Teleostei):
      rationalized tools in fish population biology.
AB  - We report the isolation and sequencing of 400-550 base pairs (bp) of the
      mitochondrial DNA (mtDNA) control region of eight species of Sparidae
      (Perciformes, Teleostei). This sequence information allowed us to design specific
      primers to one of these species (Pagellus bogaraveo). The new set of primers was
      used to test a rationalized approach to study the mtDNA nucleotide variability at
      the intraspecific level. The single-strand conformation polymorphism (SSCP)
      technique was applied to detect sequence variation in two non-overlapping
      fragments of the control region of 32 individuals of P. bogaraveo. To assess the
      sensitivity of the method, the nucleotide sequence of the analysed region was
      determined for all the specimens. The results showed that, for one of the two
      fragments, SSCP analysis was able to detect 100% of the underlying genetic
      variability. In sharp contrast, nucleotide variation of the second DNA fragment
      was completely unresolved by SSCP under different experimental conditions. This
      suggests that the resolution power of SSCP is crucially dependent on the nature
      of the fragment subjected to the analysis; therefore, a preliminary test of the
      sensitivity of the method should be performed on each specific DNA fragment
      before starting a large-scale survey. A rationalized approach, combining the SSCP
      technique and a simplified sequencing procedure, is proposed for studying
      intraspecific polymorphism at the mtDNA control region in fish.

PMID- 9022159
TI  - Lack of association of bovine MHC class I alleles with carcass and reproductive
      traits.
AB  - The present study was carried out to examine whether a relationship between
      bovine major histocompatibility complex (BoLA) class I alleles and carcass traits
      or reproductive performance exists in Braunvieh and Fleckvieh AI (artificial
      insemination) bulls. The influence of BoLA class I (BoLA-A) alleles on
      deregressed breeding values for net growth rate, carcass index and thigh volume
      was assessed in Braunvieh crosses and Fleckvieh bulls with a gene substitution
      model. The reproductive traits: non-return rate and interval between first and
      last insemination of daughters (female fertility), as well as non-return rate of
      inseminated cows (male fertility), were only investigated in Fleckvieh animals.
      No influence of the BoLA-A region on the traits evaluated could be demonstrated.
      An improper, i.e. less restrictive analysis would have led to spurious results.

PMID- 9022160
TI  - A bovine polymorphic microsatellite locus IDVGA68 (D16S23) assigned to BTA 16.

PMID- 9022161
TI  - Detection of four porcine Y-specific markers by RAPD.

PMID- 9022162
TI  - Polymorphism characterization of five canine microsatellites.

PMID- 9022163
TI  - A caprine dinucleotide repeat: microsatellite CHI AE54.

PMID- 9022164
TI  - A PCR-based diagnostic test for the endogenous retroviral element ev-B6 of
      chickens.

PMID- 9022165
TI  - Dinucleotide polymorphism at the bovine potassium voltage gated channel locus
      (KCNA4).

PMID- 9022166
TI  - A diallelic tetranucleotide repeat, (GT3)5 or 6, within intron 1 of the ovine
      interferon-gamma-gene.

PMID- 9022167
TI  - Sequencing of a novel cDNA and mapping to bovine chromosome 3 by single-strand
      conformation polymorphism (SSCP).

PMID- 9022168
TI  - Two microsatellites on pig chromosome 7.

PMID- 9022169
TI  - A polymorphic porcine dinucleotide repeat S0532 (BHT487) at chromosome 13q48.

PMID- 9022170
TI  - A polymorphic porcine dinucleotide repeat S0531 (BHT10) at chromosome 1p22.

PMID- 9022171
TI  - Anonymous sheep microsatellite markers McM4, McM105, McM126, McM380, McM541 and
      McM554.

PMID- 9022172
TI  - Four polymorphic microsatellites in turbot Scophthalmus maximus.

PMID- 9022173
TI  - Mapping two bovine marker loci, IDVGA66 (D16S34) and IDVGA76 (D14S35) by SSCP.

PMID- 9022175
TI  - Progress towards an alanine/ESR therapy level reference dosimetry service at NPL.
AB  - This paper describes work being carried out at the National Physical Laboratory
      towards the establishment of an alanine reference dosimetry service for
      radiotherapy applications. A precision fused quartz holder has been constructed
      to allow precise positioning of alanine dosimeters in the ESR cavity. A novel
      method of signal analysis based on spectrum fitting has been developed to
      minimize the effect of baseline distortions. Data are also presented on the
      relative response of alanine to 60Co gamma rays and high energy photons (4-12
      MeV).

PMID- 9022176
TI  - One year of experience with alanine dosimetry in radiotherapy.
AB  - Commercially available alanine dosimeters from different manufacturers were
      purchased for this study. The response of the detectors was evaluated with 60Co
      gamma radiation in the dose range 0.2-200 Gy, using a small EPR spectrometer
      dedicated to dosimetry. The batch sensitivity, inter-specimen scattering and
      background signal for the different selection of dosimeters were evaluated. The
      usefulness of the alanine dosimetry system for clinical routine is illustrated by
      in vivo measurements during 192Ir brachytherapy of cervix carcinoma.

PMID- 9022177
TI  - Alanine-ESR in vivo dosimetry: a feasibility study and possible applications.
AB  - A new alanine-ESR dosimeter has been developed at AERIAL in order to study its
      potential use in radiotherapy. Alanine-ESR results are compared with ion chamber
      for depth-dose measurements. A good concordance has been found between
      provisional dosimetry and absorbed dose during high dose rate and intra operative
      treatments. The results of the experiments indicate that alanine-ESR dosimetry is
      suited to check dose optimisation routines and seems to be a promising in vivo
      dosimetry technique.

PMID- 9022178
TI  - Alanine-ESR dosimetry for radiotherapy. IAEA experience.
AB  - At present, the most commonly used transfer dosimeters for radiotherapy
      applications are TL dosimeters. They are being used for intercomparison between
      SSDLs (about 70) and the IAEA dosimetry laboratory. However, there are some
      undesirable characteristics of this dosimetry system. We have a study in progress
      at the IAEA to evaluate the alanine-ESR system as an alternative to TLDs. There
      are several desirable qualities which make alanine an attractive dosimeter.
      Preliminary data suggest that the alanine-ESR dosimetry system has the potential
      to replace TLDs for intercomparison amongst SSDLs in the therapy-level dose
      region.

PMID- 9022179
TI  - The extension of the range of NIM alanine/ESR dosimetric system to therapy level.
AB  - The NIM alanine/ESR dosimetric system, which was designed for industrial
      radiation processing, has been improved to be suited for applications in therapy
      dose range. Two different procedures of dose intercomparisons between IAEA and
      NIM were carried out with the improved system in the range of 2.5 to 100 Gy. In
      the first procedure, a set of NIM alanine dosimeters were irradiated at IAEA
      dosimetric laboratory and part of dosimeters marked "for evaluated" were
      evaluated using the rest of those with "known dose" given by IAEA. Most of
      evaluated doses agreed with IAEA doses within 1%. In the second procedure, all
      above dosimeters were evaluated on the base of NIM dosimetry. The results
      indicated that the doses determined by NIM agreed with those given by IAEA within
      3% on the average.

PMID- 9022180
TI  - Alanine EPR dosimeter response in proton therapy beams.
AB  - We report a series of measurements directed to assess the suitability of alanine
      as a mailable dosimeter for dosimetry quality assurance of proton radiation
      therapy beams. These measurements include dose-response of alanine at 140 MeV,
      and comparison of response vs energy with a parallel plate ionization chamber.
      All irradiations were made at the Harvard Cyclotron Laboratory, and the
      dosimeters were read at NIST. The results encourage us that alanine could be
      expected to serve as a mailable dosimeter with systematic error due to
      differential energy response no greater than 3% when doses of 25 Gy are used.

PMID- 9022181
TI  - A response of L-alpha-alanine and standard bone powder on 3.4 MeV/amu 59Co ion
      beams.
AB  - Dosimetric response of microcrystaline L-alpha-alanine and standard bovine bone
      powder on 3.4 MeV/amu 59Co ions (LET approximately 5500 eV/nm) was investigated.
      The long-lived paramagnetic centers created by ion beams were measured after 51
      and 420 days. Relative sensitivity compared to gamma rays was estimated at 0.2
      for L-alpha-alanine and 0.15 for standard bovine bone powder.

PMID- 9022182
TI  - Multifrequency electron paramagnetic resonance of irradiated L-alanine.
AB  - The radical generated by gamma-irradiation of crystalline L-alanine was examined
      by continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) at 1.8,
      3.2, 4.9, 9.1 and 19.4 GHz. The spin-flip satellite lines that make a prominent
      contribution to the saturated spectra at 9.1 GHz are less conspicuous at lower
      frequencies because of overlap with the allowed transitions. The spin-lattice
      relaxation times measured by long-pulse saturation recovery and phase memory
      times measured by electron spin echo increase with increasing microwave
      frequency.

PMID- 9022183
TI  - Numerical signal treatment for optimized alanine/ESR dosimetry in the therapy
      level dose range.
AB  - Electron spin resonance (ESR) spectra of alanine detectors irradiated to absorbed
      doses below 5 Gy are affected by a varying non-linear background which mainly
      influences the lower limit of detection in alanine/ESR dosimetry. A mathematical
      method based on fast Fourier transform is described capable of filtering
      simultaneously background and noise in the frequency domain of ESR spectra. It
      provides clearer alanine/ESR signals down to 50 mGy. Even in non-irradiated but
      long-term stored alanine detectors an ESR signal could be observed similar to
      irradiated alanine (pre-signal). A linear ESR signal vs absorbed dose
      relationship was found above 200 mGy, after correction for background and pre
      signal. The number of repeated ESR read-out cycles and hence the time required
      for a precise and reliable low-dose evaluation have significantly been reduced.
      The method has been worked out for the therapy-level dosimetry range and tested
      on a Bruker ESP 300 and for comparison Bruker EMS 104 ESR spectrometer.

PMID- 9022184
TI  - Verification of occupational doses at the first nuclear plant in the former
      Soviet Union.
AB  - Mean annual occupational exposures are reported for radiation workers at the
      first Russian industrial nuclear facility 'Mayak', South Ural region, for the
      period 1948-1988. The underlying individual doses originate from the register of
      the in-plant radiation safety department and are based on local film dosimetry
      results. Differentiation is made between personnel working at reactor and
      radiochemical processing plants. Verification of summed film doses is performed
      by means of ESR dose reconstruction using extracted teeth from selected
      individuals. Explanations are given for observed discrepancies between the
      reconstructed individual doses and original integrated film dosimetry results.
      The research potential of combined dose information from specific tooth enamel
      and dentine are shown.

PMID- 9022185
TI  - The first international intercomparison of EPR-dosimetry with teeth: first
      results.
AB  - Intercomparison of EPR-dosimetric techniques using tooth enamel had been
      performed in order to check whether the results produced by different
      laboratories are consistent and accurate. Participants were supposed to evaluate
      doses applied to pulverized enamel samples, using routine techniques from their
      laboratories. The intercomparison has demonstrated a great variety of methods
      used for dose reconstruction. Peculiarities of experimental approaches are
      discussed systematically in terms of procedure for recording the EPR-spectra,
      determination of the amplitude of the radiation induced signal, determination of
      the dose, and error propagation.

PMID- 9022186
TI  - An approach to the assessment of overall uncertainty of determination of dose
      using an ESR technique.
AB  - An approach to the assessment of overall uncertainty of dose reconstruction by
      means of an ESR with additive dose technique is proposed. This approach takes
      account of uncertainties caused by different sources giving a quantitative
      measure of uncertainty of the determined dose. Dose is determined as an interval
      assessment rather than a deterministic value, allowing for the analytical
      estimation of both the mean value and the 95% confidence intervals. The effects
      of the number of additional irradiations and the value of dose increment on the
      uncertainty of dose determination are analyzed.

PMID- 9022187
TI  - Aspects of retrospective ESR dosimetry (invited paper).
AB  - A review is given on the major technological and methodological aspects of
      retrospective ESR dosimetry with tooth enamel. Topics include the collection and
      preparation of samples, the evaluation, treatment and interpretation of the ESR
      signals, and the procedure of dose reconstruction. Two pathways are described to
      differentiate between doses from different internal and external sources. They
      are based on dose comparisons as evaluated from different tooth issues or from
      dose vs age dependencies obtained by ESR dosimetry from populations with
      different exposure conditions. The concepts given are illustrated by recently
      achieved ESR doses that were reconstructed from teeth of radiation workers and
      members of the public of the Southern Urals region, Russia.

PMID- 9022188
TI  - Tooth enamel as a detector material for retrospective EPR dosimetry.
AB  - Different methods of spectra evaluation and dose reconstruction in retrospective
      EPR dosimetry with tooth enamel have been compared in this study. Experiments
      with teeth irradiated with known doses have shown that dosimetry above 1 Gy using
      a dose effect curve is, with a standard deviation of 10%, the best method. As a
      second result it is shown that dosimetry down to 100 mGy with a standard
      deviation of 15% is possible.

PMID- 9022190
TI  - Optimal registration conditions for tooth EPR dosimetry at low accumulated dose.
AB  - The spectrum registration under rapid passage conditions (the second harmonic
      phase quadrature of the absorption signal) allows one to enhance substantially
      the sensitivity of tooth enamel and bone EPR dosimetry at a low accumulated dose.
      In the present work the dependencies of the radiation and background signals on
      EPR spectrometer parameters are described and the optimal conditions in RPM for
      EPR dosimetry are obtained.

PMID- 9022189
TI  - Preparation-induced errors in EPR dosimetry of enamel: pre- and post-crushing
      sensitivity.
AB  - Polyakov et al. (1995) showed errors in dose estimation as a function of grain
      size for enamel grains given beta irradiation after crushing. We tested the
      effect of gamma irradiation applied to the specimens before and after crushing.
      We confirmed Polyakov's observations and found that post-crushing irradiation
      altered the slope of the dose-response curve of the hydroxyapatite signal and
      produced a grain-size-dependent offset. No changes in the slope of the dose
      response curve were seen in enamel caps irradiated whole before crushing.

PMID- 9022191
TI  - Metamorphic modifications and EPR dosimetry in tooth enamel.
AB  - It is shown that metamorphic modifications in tooth enamel have an essential
      influence on the results of EPR dosimetry. The metamorphic modifications in
      minerals of biological origin proceed more quickly than in usual natural
      minerals. The approaches which at present are applied for reconstruction of doses
      connected with Chernobyl accident need additional investigation.

PMID- 9022192
TI  - Estimation of accumulated dose of radiation by the method of ESR-spectrometry of
      dental enamel of mammals.
AB  - ESR-spectrometry was used to investigate radiation-induced paramagnetic centers
      in enamel of mammals: carnivores (polar bear and fox), ungulates (reindeer,
      European bison, moose), and man. Values at half the microwave power saturation of
      the radiation signal, P1/2, evaluated at room temperature, was found to range
      from 16 to 26 mW for animals and man. A new approach to discrimination of the
      radiation induced signal from the total ESR spectrum of reindeer enamel is
      proposed. 'Dose-response' dependencies of enamel of different species mammals
      were measured within the dose range from 0.48 up to 10.08 Gy. Estimations of
      'radiosensitivity' enamel of carnivores and ungulates showed good agreement with
      radiosensitivity enamel of man by ESR method.

PMID- 9022193
TI  - Gamma-ray dose assessment after the 1994 radiation accident in Kiisa (Estonia):
      preliminary results.
AB  - Dose reconstruction using thermoluminescence (TL) of quartz, extracted from the
      ceramic plant pots, and using EPR of the sugar samples, was performed after the
      1994 radiation accident in the village Kiisa (Estonia). A gamma-ray source 137Cs
      was located during approx. 28 days in one of the village dwelling houses. On the
      basis of preliminary results, some important details of the history of the
      accident have been clarified. It was shown, that the gamma-ray source most of the
      time was placed in the kitchen table drawer. Thus, the absorbed dose rate of
      whole-body exposure for three inhabitants of the house in Kiisa was defined by
      this location of the source.

PMID- 9022195
TI  - Radiation dosimetry of an accidental overexposure using EPR spectrometry and
      imaging of human bone.
AB  - On 11 December 1991 a radiation accident occurred at an industrial accelerator
      facility. A description of the facility and details of the accident are reported
      in Schauer et al., 1993a). In brief, during maintenance on the lower window
      pressure plate of a 3 MV potential drop accelerator, an operator placed his
      hands, head, and feet in the radiation beam. The filament voltage of the electron
      source was turned 'off', but the full accelerating potential was on the high
      voltage terminal. The operator's body, especially his extremities and head, were
      exposed to electron dark current. At approx. 3 months post-irradiation, the four
      digits of the victim's right hand and most of the four digits of his left hand
      were amputated. Electron paramagnetic resonance (EPR) spectrometry was used to
      estimate the radiation dose to the victim's extremities. Extremity dose estimates
      ranged from 55.0 Gy (+/- 4.7 Gy) to 108 Gy (+/- 24.1 Gy).

PMID- 9022194
TI  - ESR dosimetry of a deceased radiation worker.
AB  - A case of overexposure of an industrial radiographer using 192Ir sources and
      having a filmbadge dosimeter record of 104 mSv has been examined with ESR
      dosimetry of postmortem tooth and bone specimens. ESR measurements of the tooth
      enamel showed an intense signal of CO2- and gave the equivalent dose (ED) of 14
      Gy by the additive dose method using gamma-rays from a source of 60Co. The doses
      for a finger bone and humerus were 14.7 and 7.0 Gy, respectively. It was
      concluded that he had been exposed to radiation repeatedly over 10 yr and that
      ESR dosimetry can give a life-long cumulative dose for personnel using radiation.

PMID- 9022196
TI  - EPR-based dosimetry of large dimensional radiation fields (Chernobyl experience
      and new approaches).
AB  - On the basis of EPR signal investigations using irradiated materials as gamma
      radiation sensors, the method of dimensionally quasi-continual dosimetric long
      cords was developed and applied in the investigation of the destroyed Chernobyl
      Unit-4. The study of irradiated quartz with different initial and post
      irradiation defect concentrations is discussed for dosimetric practical use as
      well as for fundamental understanding.

PMID- 9022198
TI  - Radiation induced paramagnetic centers in human tooth enamel as studied by ENDOR.
AB  - ENDOR and ENDOR-induced-EPR techniques were applied to a study of radiation
      defects in human tooth enamel. Matrix ENDOR signal was observed correspondent to
      minimal distances from paramagnetic center to 1H nuclei of 5.5 A and 31P that of
      6 A. A hole in 1H ENDOR spectrum taken from the left wing of EPR line appears at
      high dose, which was tentatively ascribed to a part of traps with disturbed
      spatial properties by surrounding radiation defects.

PMID- 9022197
TI  - ESR and TL dosimetry systems: comparative measurements for human phantom.
AB  - Mixtures of small fragments of tooth enamel as well as thermoluminescence (TL)
      dosimeters were placed into the tissue-equivalent phantom of the human head with
      skeleton (approximately at the level of the jaws) and irradiated using 137Cs low
      dose-rate gamma therapeutic sources ('SELEKTRON' LDR 137Cs). Phantom, samples of
      teeth and TL detectors were irradiated behind water tank to produce scattered
      irradiation. The same irradiation with the same geometry was performed in air
      too. For gamma-spectrometry 137Cs sources with very low activity were used but
      with the same geometry as therapeutic sources. The absorbed dose in enamel was
      estimated with the help of ESR spectrometer 'ESP-300 E' (Brucker). The samples of
      tooth enamel were partially used for preliminary dose evaluation by ESR signal
      before starting of experiment. TL dosimetry was performed by TL reader model 8800
      (HARSHAW) using TL dosimeters calibrated with 137Cs. The paper presents data
      obtained in comparative aspects.

PMID- 9022199
TI  - Proton dosimetry in bone using electron spin resonance.
AB  - We have studied the ESR response of proton-irradiated (in vitro) bone. The ESR
      response as a function of proton (E = 105 MeV) dose to bone was linear from 0 to
      50 Gy and similar to the photon (E = 6 MV) dose response. The ESR depth response
      (Bragg) curve was depressed as compared to a depth-response curve determined with
      a parallel plate ionization chamber (PPIC). There was a short-term ESR signal
      fade in the Bragg peak region, likely attributable to the organic component in
      bone. We are continuing to investigate these latter two effects.

PMID- 9022200
TI  - A 3D- and 4D-ESR imaging system for small animals.
AB  - A new version of in vivo ESR-CT system composed of custom-made 0.7 GHz ESR
      spectrometer, air-core magnet with a field-scanning coil, three field-gradient
      coils, and two computers enables up- and down-field, and rapid magnetic-field
      scanning linearly controlled by computer. 3D-pictures of distribution of
      nitroxide radicals injected in brains and livers of rats and mice were obtained
      in 1.5 min with resolution of 1 mm. We have also succeeded in obtaining spatial
      time imagings of the animals.

PMID- 9022201
TI  - Current status of the EPR method to detect irradiated food.
AB  - This review gives a brief outline of the principles of the EPR detection method
      for irradiated foods by food type. For each food type, the scope, limitations and
      status of the method are given. The extensive reference list aims to include all
      which define the method, as well as some rarely cited works of historical
      importance.

PMID- 9022202
TI  - Influencing factors on ESR bone dosimetry.
AB  - This paper reports on the influence that temperature during irradiation and dose
      rate have on the radiation-induced free-radical yield and time stability in non
      de-proteinized bone. Bone from chicken legs was irradiated in the 253-293 K
      temperature range and with two different sources (60Co, 0.6 Gy/s and 12 MeV
      electrons, 6 x 10(6) Gy/s). Temperature influences type and number of radicals,
      while radical concentration seems to slightly decrease with dose rate.

PMID- 9022203
TI  - Use of ESR for the detection of irradiated dates (Phoenix dactylifera L.).
AB  - One variety (Aple) of Libyan dry dates (Phoenix dactylifera L.) was irradiated in
      a 60Co source to absorbed doses of 0.8, 1.0, 1.5 and 2.0 kGy. Unirradiated date
      stone contains a radical with a single line g = 2.0045, feature A. Irradiation to
      a dose of 2.0 kGy (the recommended dose for fruits in U.K.) induces the formation
      of additional radicals with signals g = 1.9895 and 2.0159, feature C. The single
      line having g = 2.0045 decays in both unirradiated and irradiated samples whereas
      the additional signals g = 1.9895 and 2.0159 remain almost unchanged over a
      period of time 15 months stored at room temperature and 4 degrees C.

PMID- 9022204
TI  - Influence of sample treatment on ESR signal of irradiated citrus.
AB  - ESR spectra of the hard seed cover and kernel coating of irradiated orange and
      tangerine fruits were obtained under different sample drying conditions to
      analyze the effect of treatment on ESR line at g = 2.0033 (line A). The spectra
      shows almost the same lines that appear in stalks, achenes, seeds and skins of
      fresh fruit. The peak-to-peak intensity of the line A of the spectra shows a
      linear variation with dose in the range studied (up to 5 kGy) under controlled
      sample preparation. Q-band ESR spectra shows that this line is composed for three
      different lines from different species. A1, A2 and A3. The A2 and A3 lines are
      associated with dose but grow also during drying of the sample and are probably
      due to 'cellulosic' components of the seed cover. The A1 line appears only when
      sample is dried and is probably associated with the quinones of the internal
      kernel coat.

PMID- 9022205
TI  - Identification of irradiated mangoes by means of ESR spectroscopy.
AB  - Samples of mango varieties Tommy Atkins, Haiden and Ataulfo were irradiated with
      60Co gamma radiation at doses in the range 0.15-1.0 kGy, and stored at room
      temperature for lapses of time up to 72 h. They were then studied by ESR
      spectrometry. Results show that the ESR signal of the irradiated samples is
      higher than that of the unirradiated samples, and this is found even at the
      minimum radiation dose of 0.15 kGy. The ESR signal remained stable during the
      storage time. The ESR signals obtained for hydroheated mangoes show insignificant
      differences with respect to the control samples.

PMID- 9022206
TI  - Effect of irradiation dose, storage time and temperature on the ESR signal in
      irradiated oat, corn and wheat.
AB  - Results obtained for electron-irradiated oat, corn and wheat kernels are
      discussed. The applied irradiation doses were up to 160 kGy. For doses up to
      approx. 50 kGy the number of free radicals produced by the irradiation is linear
      with the absorbed dose; moreover, the decay at room temperature in the dark or in
      the presence of light is quite similar. These facts point to the possible use of
      these kernels as dosimeters. An analysis of the free radical decay as a function
      of time and temperature shows the contribution of at least three types of
      radicals, whose half-lifes, radiochemical yields and activation energies are
      given.

PMID- 9022207
TI  - In vivo EPR: an effective new tool for studying pathophysiology, physiology and
      pharmacology.
AB  - The development of spectrometers working at lower frequencies with improved
      resonators now permits the routine use of non-invasive EPR spectroscopy in vivo.
      The capabilities of EPR spectra to reflect environmental conditions, combined
      with the use of paramagnetic materials as selective non-toxic labels, has led to
      increasingly widespread and productive applications of the technique to complex
      problems involving physiology, pharmacology and pathophysiology. Some of the
      especially promising applications in which EPR techniques uniquely appear to
      provide valuable information are illustrated, including the measurement of oxygen
      and oxygen gradients, monitoring of the metabolism of xenobiotics, monitoring
      pharmacokinetics of drugs, measurement of perfusion, measurement of pH,
      recognition and labeling of receptors, and characterization of drug releasing
      systems.

PMID- 9022208
TI  - Gamma-sterilization-induced radicals in biodegradable drug delivery systems.
AB  - Electron paramagnetic resonance (EPR) spectroscopy (1.2 and 9.25 GHz, 25 degrees
      C) was used to characterize free radicals in gamma-ray sterilized biodegradable
      polymers of the type which are in clinical use. Free radicals were detected in
      all irradiated polymer samples. The temperature of irradiation (25 degrees C vs
      dry ice temperature) had only a minor influence on the yield of radicals and the
      shape of the EPR spectra. In contrast, the composition of the polymers and the
      drugs incorporated in them did strongly influence the amount of radiation-induced
      free radicals and their reactivity. In general, polymers with high melting points
      and crystallinity had the highest yields of radicals observable at room
      temperature. We were able to use the free radicals induced by the usual
      sterilization procedures to follow the penetration of water and the degradation
      of the polymers in vitro and in vivo. The ability of in vivo EPR to follow drug
      delivery noninvasively and continuously in vivo, using the free radicals induced
      in the usual sterilization process indicates that this approach could be applied
      immediately for the characterization of these drug delivery systems in
      experimental animals and in the near future should be able to be used in human
      subjects.

PMID- 9022209
TI  - EPR/ENDOR investigations of gamma-irradiated steroid hormone single crystals.
AB  - The molecular structure of free radicals formed in certain gamma-irradiated
      steroid hormones and cholesterol determined by electron spin resonance (ESR) and
      electron nuclear double resonance studies has been reviewed. The influence of
      intermolecular interactions and hydrogen bonds on the structure of the radicals
      formed, as well as the effect of substitution of hydroxyl group on the alpha
      hyperfine splitting tensor have also been analyzed.

PMID- 9022210
TI  - The effect of lethal doses of radiation in vivo on the lipid microviscosity of
      tumor nuclear membranes.
AB  - The changes in the microviscosity of the nuclear membranes of tumor and liver
      cells of tumor hosts with developing Erlich ascites carcinoma at different times
      after irradiation of lethal dose has been studied by spin probe method. Using two
      iminoxyl radicals localized in various lipid regions, it was shown that the
      character and degree of changes in microviscosity, estimated from rotational
      correlation time for spin probes, indicate the different response to irradiation
      of liver and tumor cells.

PMID- 9022211
TI  - In vivo autoradiography of radioiodinated (R)-3-quinuclidinyl (S)-4-iodobenzilate
      [(R, S)-IQNB] and (R)-3-quinuclidinyl (R)-4-iodobenzilate [(R,R)-IQNB].
      Comparison of the radiolabelled products of a novel tributylstannyl precursor
      with those of the established triazene and exchange methods.
AB  - Radioiodinated (R,S)-IQNB and (R,R)-IQNB are prepared either from a triazene
      precursor or using an exchange reaction. In both cases the radiochemical yield is
      low. The product of the exchange reaction also suffers from having a fairly low
      specific activity. A new method for preparing radioiodinated (R,S)-IQNB and (R,R)
      IQNB from a tributylstannyl precursor has recently been developed. This method is
      more convenient and much faster than the triazene and exchange methods, and it
      reliably results in a high radiochemical yield of a high specific activity
      product. In rat brain, the in vivo properties of the radioiodinated products of
      the tributylstannyl method are identical to those of the corresponding
      radioiodinated (R,S)-IQNB and (R,R)-IQNB prepared using the triazene and exchange
      methods. Dissection studies of selected brain regions show that at 3 h post
      injection (R,S)-[125I]IQNB prepared by all three methods have indistinguishable %
      dose g-1 values in all brain regions studied. Autoradiographic comparison of
      coronal slices through the anteroventral nucleus of the thalamus, through the
      hippocampus and through the pons at 2 h post injection shows that (R,S)
      [125I]IQNB prepared by the triazene and tributylstannyl methods have
      indistinguishable patterns of binding.

PMID- 9022212
TI  - Validation of the limulus amebocyte lysate (LAL) test for routine PET
      radiopharmaceuticals.
AB  - The kinetic turbidimetric limulus amebocyte lysate test was validated as method
      for detecting endotoxins in short-lived radiopharmaceutical samples. Using this
      method, radiopharmaceuticals can be released for administration to humans after
      the test, without extensive loss of radioactivity. Inhibition or enhancement on
      the LAL results by the product samples were examined in more detail and
      eliminated.

PMID- 9022213
TI  - A rather intense source of fast neutrons for small scale activation.
AB  - A thick beryllium target has been developed for installation onto a small proton
      cyclotron (CTI RDS 112), providing an intense source of fast neutrons for
      activation purposes. Careful attention was paid to cooling and irradiation
      geometry, allowing cubic centimeter scale samples to approach the proton beam
      strike surface to within 5 mm. This proximity assures approximately equal to
      10(11) neutron/s passing through the irradiated sample when 20 microgramsA of 11
      MeV protons are incident on the beryllium primary target.

PMID- 9022214
TI  - Effect of gamma radiation on the survival of fungal and actinomycetal florae
      contaminating medicinal plants.
AB  - This study evaluates the effect of gamma radiation on the viability of fungi and
      actinomycetes that contaminate medicinal plants. The relationship between the
      total lipids of some fungi and actinomycetes and their sensitivity to gamma
      radiation is also investigated. The date reveal that the viable counts of these
      florae decrease approximately exponentially with the radiation dose, the
      effective dose for the elimination of these microorganisms being about 5 kGy for
      all the medicinal plants under study. Response of pure cultures of fungi and
      actinomycetes isolated from medicinal plants to increasing absorbed doses of
      gamma radiation indicate that an increase in radioresistance is in the following
      order: Streptomyces rimosus, Fusarium solani, Nocardia kuroishii. F. oxysporum,
      A. fumigatus, A. flavus, A. parasiticus and A. ochraceus. The total lipid
      contents of molds and actinomycetes have been reported to be increased by
      increasing the radio-resistance of microorganisms, and hence there is a
      relationship between the radio-sensitivity of microorganisms and the total lipid
      mass of flora mycelia.

PMID- 9022215
TI  - Availability of essential trace elements in Ayurvedic Indian medicinal herbs
      using instrumental neutron activation analysis.
AB  - Specific parts of several plants (fruits, leaves, stem, bark, and roots) often
      used as medicines in the Indian Ayurvedic system have been analysed for 20
      elements (As, Ba, Br, Ca, Cl, Co, Cr, Cu, Fe, K, Mn, Mo, Na, P, Rb, Sb, Sc, Se,
      Sr and Zn) by employing instrumental neutron activation analysis (INAA). The
      samples were irradiated with thermal neutrons in a nuclear reactor and the
      induced activity was counted using high resolution gamma ray spectrometry. Most
      of the medicinal herbs have been found to be rich in one or more of the elements
      under study.

PMID- 9022216
TI  - Discriminant analysis of normal and malignant breast tissue based upon INAA
      investigation of elemental concentration.
AB  - Discriminant analysis of six trace element concentrations measured by
      instrumental neutron activation analysis (INAA) in 26 paired-samples of malignant
      and histologically normal human breast tissues shows the technique to be a
      potentially valuable clinical tool for making malignant-normal classification.
      Nonparametric discriminant analysis is performed for the data obtained. Linear
      and quadratic discriminant analyses are also carried out for comparison. For this
      data set a formal analysis shows that the elements which may be useful in
      distinguishing between malignant and normal tissues are Ca, Rb and Br, providing
      correct classification for 24 out of 26 normal samples and 22 out of 26 malignant
      samples.

PMID- 9022217
TI  - Kinetics of phosphatidylinositol-specific phospholipase C with vesicles of a
      thiophosphate analogue of phosphatidylinositol.
AB  - 1,2-Dimyristoyloxypropane-3-thiophospho(1D-1-myo-inositol) (D-thio-DMPI) was
      synthesized as a substrate for the continuous spectrophotometric assay of
      phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus cereus.
      Release of thio-diglyceride is followed by a coupled reaction with 4,4'
      dithiopyridine to produce a chromophore, 4-thiopyridine, measured by its
      absorption at 324 nm. Sonicated vesicles of D-thio-DMPI gave sigmoidal Michaelis
      Menten kinetics with PI-PLC as a function of bulk concentration of substrate
      (Hill plot: Vmax = 132 mumol min-1 mg-1, apparent Km = 0.115 mM, h = 1.8).
      Addition of dimyristoyl phosphatidylcholine (DMPC) or dimyristoyl
      phosphatidylmethanol to vesicles of D-thio-DMPI resulted in an initial increase
      in rate followed by a decrease at higher concentrations of non-substrate lipid.
      Binding of PI-PLC to vesicles of DMPC with 10 mol% of N-dansyl
      phosphatidylethanolamine was demonstrated by fluorescence resonance energy
      transfer from tryptophan in the enzyme to the dansyl lipid probe.

PMID- 9022219
TI  - Effects of distearoylphosphatidylglycerol and lysozyme on the structure of the
      monoolein-water cubic phase: X-ray diffraction and Raman scattering studies.
AB  - X-ray diffraction and Raman scattering spectroscopy have been used to study phase
      transitions and changes in molecular organization of the cubic Pn3m monoolein
      (MO)-H2O phase upon introducing low amounts of distearoylphosphatidylglycerol
      (DSPG) and lysozyme (LSZ). X-ray diffraction measurements indicated a phase
      transition Pn3m-Im3m brought about by DSPG and LSZ, however DSPG also induced
      formation of the lamellar phase. Raman spectra have demonstrated that
      incorporation of DSPG into the lipid bilayer decreases the mobility of acyl
      chains and increases the number of hydrogen-bonded C=O groups of MO. On the other
      hand, LSZ exerts identical effect on the latter parameter, while no effect on the
      state of acyl chains order was observed. This result and differential scanning
      calorimetric measurements indicate that LSZ is located in the water channel
      system of the cubic phase. The results are discussed on the basis of an infinite
      periodical lipid bilayer structure and lipid parameter concepts.

PMID- 9022220
TI  - Bicontinuous cubic phase: a model for investigating the effects on a lipid
      bilayer due to a foreign substance.
AB  - Biological effects of foreign substances are usually caused by their interaction
      within lipid bilayers with the membrane lipids. It is therefore desirable in many
      situations to determine the effects and the partition of xenobiotic substances,
      as well as drugs, added to amphiphile-water systems. Bicontinuous cubic liquid
      crystals provide three-dimensional isotropic matrices with symmetries easily
      obtained by X-ray diffraction, and were shown to be a useful tool for an initial
      investigation of the molecular properties possessed by a foreign substance. The
      concept is illustrated by adding the transdermal penetration enhancer Azone (n
      dodecyl-caprolactam) to V2-phases in the glycerol monooleate (GMO)-water system.
      The weakly polar, water immiscible, Azone is known to favour reversed types of
      phases in liquid crystals. In the present investigation, Azone was shown to
      prefer the lipid bilayer interior, with about 19% anchored in the lipid-water
      interfacial region. Some dependence of its location on water concentration was
      indicated. The unexpected swelling behaviour of monoacylglycerols in water (L2-
      >L alpha-->V2) were postulated to result from the lipids changing their polar
      headgroup conformation, thus allowing for an increase in packing parameter upon
      increasing the water content.

PMID- 9022221
TI  - Increase in hydroxy fatty acids in human low density lipoproteins with age.
AB  - The content of hydroxy fatty acids in low density lipoprotein (LDL) of healthy
      volunteers aged between 22 and 87 years without any signs of atherosclerosis or
      other age-dependent diseases was investigated. The level of hydroxy fatty acids
      obtained from LDL increases during life time: clinically healthy persons between
      56 and 66 years showed a 3- to 4-fold increase compared to young volunteers. This
      level increased in samples of probands aged 68 to 74 years compared to samples of
      young people for a factor of 10-20 and in samples of probands aged 78 to 87 years
      for a factor of 30-40. These hydroxy acids--generated mainly from hydroperoxy
      acids on linoleic acid and only partly from arachidonic acid--are obviously
      parameters of the LDL oxidation stage. About 90% of the total amount of hydroxy
      fatty acid were free fatty acids. The distribution patterns of the monohydroxy
      derivatives of linoleic and arachidonic acid indicate that they originate mainly
      from autocatalytic processes. The individual level of hydroxy acids is probably
      an indicator of the biological age.

PMID- 9022222
TI  - An integrative model for the study of developmental competencies in minority
      children.
AB  - In this article a conceptual model for the study of child development in minority
      populations in the United States is proposed. In support of the proposed model,
      this article includes (a) a delineation and critical analysis of mainstream
      theoretical frameworks in relation to their attention and applicability to the
      understanding of developmental processes in children of color and of issues at
      the intersection of social class, culture, ethnicity, and race, and (b) a
      description and evaluation of the conceptual frameworks that have guided the
      extant literature on minority children and families. Based on the above
      considerations, an integrative conceptual model of child development is
      presented, anchored within social stratification theory, emphasizing the
      importance of racism, prejudice, discrimination, oppression, and segregation on
      the development of minority children and families.

PMID- 9022223
TI  - Infant sensitivity to adult eye direction.
AB  - Adult eye direction was manipulated while adults interacted with 3-6 month-olds
      over closed-circuit television (Experiment 1) or in person (Experiment 2).
      Infants received 4 1-min interaction periods. For experimental groups, adult eye
      contact was maintained during Periods 1 and 3, and averted during Periods 2 and 4
      (by viewing infants on a television monitor to maintain contingency). Control
      infants received eye contact during all periods. Experimental infants' smiling
      declined whenever adults looked away; their visual attention simply decreased
      across periods. Control infants showed little change in gaze or smiling across
      periods. The implications of these results for Baron-Cohen's model of infant
      theory of mind and Morton and Johnson's 2-process theory of infant face
      perception are discussed.

PMID- 9022225
TI  - Children's memory of an occurrence of a repeated event: effects of age,
      repetition, and retention interval across three question types.
AB  - Children's memory of the final occurrence of a repeated event was examined
      whereby each occurrence had the same underlying structure but included
      unpredictable variations in the specific instantiations of items across the
      series. The event was administered by the children's teachers at the kindergarten
      or school. The effects of repetition (single vs. repeated event), age (4-5 vs. 6
      8-year-olds), retention interval (1 week vs. 6 weeks), and the frequency of
      specific instantiations of items were examined across 3 question types.
      Repetition increased the number of items recalled on a level that was common to
      all occurrences in response to general probes and reduced the likelihood that
      children would report details that did not occur in the event. However,
      repetition also reduced the number of correct responses about which instantiation
      was included in the occurrence and decreased the consistency of responses across
      repeated questioning. Most errors were intrusions of details from other
      occurrences; usually references to instantiations of items that had occurred
      frequently throughout the series. The younger children showed a poorer ability to
      discriminate between the occurrences than the older children, but age differences
      were less evident at the longer retention interval. The results are discussed in
      relation to current theories of memory and children's eyewitness testimony.

PMID- 9022224
TI  - Imitation or exploration? Young infants' matching of adults' oral gestures.
AB  - The claim that very young infants can imitate rests largely on reports that
      infants match adult displays of mouth opening (MO) and tongue protrusion (TP).
      Recent reviews suggest that only tongue protruding is reliably matched by young
      infants. This study tests the proposal that infants' "imitation" of tongue
      protruding reflects a coincidental match between a sight that infants find
      interesting and a behavior by which infants express interest. In Study 1, 4-week
      old infants who looked longer at a nonsocial light display also produced TPs at
      higher rates than infants showing less interest. In Study 2, 4-week-old infants
      showed more interest (looked longer at) a tongue-protruding adult face than a
      mouth-opening face. Study 3 tracked 2 infants' responses to interesting objects
      for several weeks before and after the onset of manual reaching. Both infants
      produced tongue protrusions in response to objects within reach before but not
      after reaching developed. Together, the results of the 3 studies suggest that
      infants' tongue protrusions in response to a tongue-protruding adult reflect very
      early attempts at oral exploration of interesting objects.

PMID- 9022226
TI  - Memory and processing speed in preterm children at eleven years: a comparison
      with full-terms.
AB  - This study examined the effects of prematurity on 11-year-olds' performance on 2
      specific aspects of cognition--memory and processing speed, using a new computer
      administered battery, the Cognitive Abilities Test (CAT: Detterman). Preterms
      performed more poorly than their full-term controls on all memory tasks; this
      relative deficit was associated with the presence and severity of neonatal
      Respiratory Distress Syndrome (RDS). Preterms were also slower on selected
      aspects of processing speed but not on motor speed. Memory and processing speed,
      taken together, accounted for much of the 10-point difference in WISC-R IQ
      between groups.

PMID- 9022227
TI  - Development of arithmetical competencies in Chinese and American children:
      influence of age, language, and schooling.
AB  - The arithmetical competencies of more than 200 Chinese or American kindergarten,
      first-, second-, or third-grade children were assessed toward the beginning and
      toward the end of the U.S. school year. All children were administered a paper
      and-pencil test of addition skills, a digit span measure, and an addition
      strategy assessment. The addition strategy assessment provided information on the
      types of strategies the children used to solve simple addition problems as well
      as information on the speed and accuracy of their strategy use. Information on
      the number of math instruction periods across times of measurement was also
      obtained for each of the first-, second-, and third-grade children. The pattern
      of arithmetical development across the academic year and across the Chinese and
      American children suggests that a mix of cultural and maturational factors
      influence the emergence of early arithmetical competencies and that the Chinese
      advantage in early mathematical development is related to a combination of
      language- and school-related factors.

PMID- 9022228
TI  - Seriation, conservation, and theory of mind abilities in individuals with autism,
      individuals with mental retardation, and normally developing children.
AB  - Seriation, conservation, and theory of mind abilities were examined in
      individuals with autism (N = 16), mental retardation (N = 16), and in normally
      developing children (N = 16). Seriation tasks included seriation of tubes,
      blocks, and flat squares. Conservation tasks included conservation of area,
      number, substance, quantity, and weight. Theory of mind tasks involved predicting
      false belief and understanding value and fact beliefs. Participants with autism
      performed better than participants with mental retardation on seriation, while no
      differences emerged between these groups on conservation and false belief.
      Individuals with autism performed less well than individuals with mental
      retardation on the value and fact belief tasks; however, when verbal ability was
      held as a covariant, the difference was no longer significant. Normally
      developing children performed better than the other two groups on all tasks.
      These results suggest that autism does not involve a specific impairment in
      theory of mind and that theory of mind deficits are not unique to autism.

PMID- 9022229
TI  - Imitation and pantomime in high-functioning adolescents with autism spectrum
      disorders.
AB  - A study was designed to test 2 alternative hypotheses--a symbolic hypothesis and
      an executive function hypotheses--for the imitation and pantomime deficits found
      in previous studies of autism. The subjects were 17 adolescent high-functioning
      subjects with autism spectrum disorders and 15 clinical comparison subjects who
      were matched on chronological age and verbal IQ. Meaning and sequence were
      manipulated in facial and manual imitation tasks. Sequence was manipulated in the
      pantomime and control tasks. Recognition memory and motor control tasks were
      matched to the experimental tasks. The results provided no support for the
      symbolic deficit hypothesis; meaning aided rather than hindered the performance
      of the group with autism. Partial support for the executive deficit hypothesis
      was found. There were no group differences on motor control tasks, and few on the
      memory control tasks, arguing against deficits in motor initiation, basic motor
      coordination, or visual recognition memory.

PMID- 9022230
TI  - Social responsivity: judging signals of young children with and without
      developmental delays.
AB  - This was an experimental study of the ability of adults to detect 1 social signal
      that is important in social interactions, children's glances or looks at their
      social partners. Adult judges were either parents of children with developmental
      delays, parents of nondelayed children, or nonparents with little experience with
      children. Each participant viewed 120 videotaped episode in which very young
      children's looks (of 2 types, either a focus on parent's face or nonface focus)
      occurred or no looking occurred. Half the episodes featured children with
      documented developmental delays and half featured nondelayed children.
      Participants made judgments about the occurrence of a look in each episode and
      rated their confidence in each judgment. Participants made more accurate and
      quicker responses to social looks by children without than those with
      developmental delays. Accuracy effects were qualified by interactions with type
      of look. Participants were more confident of their judgments of looks for
      nondelayed toddlers than those with delays. Signal detection statistics indicated
      that looks of delayed toddlers were harder to identify and that judges set a more
      stringent criterion for responding to those looks. No effects of judges' level of
      experience with delayed or nondelayed children were found. Implications of these
      findings for social interaction involving individuals with developmental delays
      are discussed.

PMID- 9022231
TI  - Referring and reporting research participants at risk: views from urban
      adolescents.
AB  - Researching developmental risks of urban youth raises ethical concerns when an
      investigator discovers a participant is in jeopardy. This study collected data on
      147 seventh, ninth, and eleventh graders' views of 3 investigator options: (1)
      taking no action and maintaining confidentiality, (2) reporting the problem to a
      concerned parent or adult, and (3) facilitating adolescent self-referrals.
      Participants judged these options within the context of 5 risk domains: substance
      abuse, child maltreatment, life-threatening behaviors, delinquency, and shyness.
      Judgments of reporting options were related to grade and ratings of risk
      severity, but not to moral reasoning. Confidentiality was viewed favorably for
      risk behaviors of low perceived severity or for which the consequences of adult
      discovery might introduce greater risk. Confidentiality was viewed unfavorably
      and reporting to adults favorably for child maltreatment and threats of suicide.
      Self-referral was viewed favorably across all grades and risk behaviors.
      Implications of adolescent perspectives for research ethics are discussed.

PMID- 9022232
TI  - The relationship between parenting types and older adolescents' personality,
      academic achievement, adjustment, and substance use.
AB  - The purpose of the present study was to examine Baumrind's T3 conceptual
      framework using a multiple informant design and an older adolescent population.
      With 178 college students and their families as participants, the present study
      found many of the predicted relations between parents' child-rearing style
      (Authoritative, Democratic, Nondirective, Nonauthoritarian-Directive,
      Authoritarian-Directive, and Unengaged) and their adolescent children's behavior
      in the 4 domains assessed: personality, adjustment, academic achievement, and
      substance use. The differences between parenting types on the criterion measures
      were not as large as reported in Baumrind's study, and significant effects were
      predominantly due to the poor scores from children with Unengaged and
      Authoritarian-Directive parents. The results are discussed in terms of their
      implications for the Authoritative parenting type, the utility of using a
      typology, and areas for future research.

PMID- 9022233
TI  - Neither too sweet nor too sour: problem peers, maternal control, and problem
      behavior in African American adolescents.
AB  - This study examined whether maternal control protects African American
      adolescents from the negative influence of problem peers. Two forms of control
      were examined, behavioral control and psychological control. It was hypothesized
      that there would be a curvilinear relation between control and adolescent problem
      behavior, with the strength of the relationship and the amount of control optimal
      for adolescent development varying by the level of peer problem behavior. In
      general, data supported this model, particularly in regard to behavioral control,
      where the predicted curvilinear interaction occurred even after controlling for
      initial levels of problem behavior. The predicted curvilinear interaction between
      psychological control and peer problem behavior was statistically significant if
      initial levels of problem behavior were not controlled for but was not
      significant after controlling for initial problem behavior. These findings
      suggest that high-quality parenting can play a modest but critical role in the
      face of environmental adversity.

PMID- 9022234
TI  - Not just "ghosts in the nursery": contemporaneous intergenerational relationships
      and parenting in young African-American families.
AB  - The association of the mother-grandmother relationship with parenting of
      preschoolers was examined in a sample of 96 African-American multigenerational
      families. Mother-grandmother and parent-child interactions were assessed at home
      with videotaped problem-solving tasks. The Scale of Intergenerational
      Relationship Quality (SIRQ), a global observational coding system, was developed
      to assess the quality of the mother-grandmother relationship via observational
      ratings of mothers' and grandmothers' discussion of conflict. It yielded 4
      factors: Emotional Closeness (connectedness), Positive Affect (upbeat tone),
      Grandmother Directness (demandingness and clarity), and Individuation (balance of
      autonomy and mutuality). Regression analyses controlling for socioeconomic
      background variables showed that SIRQ factors, particularly Individuation, were
      consistently related to mothers' parenting. Relationship effects varied when
      interacted with age and coresidence. The importance of a multigenerational,
      contextual perspective for research and intervention with young African-American
      mothers is discussed.

PMID- 9022235
TI  - Sibling differences in problem behavior and parental treatment in nondivorced and
      remarried families.
AB  - This article examines within-family differences in parenting and problem behavior
      in nondivorced and remarried families, with a specific focus on whether sibling
      differences are magnified and whether the links between differential treatment
      and sibling adjustment are stronger in remarried families. Multimethod
      assessments of parenting and problem behavior were done on 516 families with 2
      same-sex adolescent siblings. The remarried families included those in which one
      or neither sibling was the mother's stepchild and one or both siblings were the
      father's stepchildren. Within-family differences in parenting and problem
      behavior were greatest in remarried families where siblings did not share the
      same biological parent. Differential treatment was also more strongly related to
      problem behavior in this family context, with the mother's biological child and
      father's stepchild at greater risk. Results are discussed in terms of the
      differing experiences of biological children and stepchildren in remarried
      households.

PMID- 9022236
TI  - Appraisals of negative events by preadolescent children of divorce.
AB  - This study investigated the appraisals of the significance of negative events
      made by 256 preadolescent children of divorce. Appraisals were assessed by a 24
      item self-report scale. Confirmatory factor analysis of this scale found support
      for a 3-dimensional model: negative self-appraisal, negative other-appraisal, and
      material loss. Differentiation between the dimensions of appraisal increased with
      age in both cross-sectional and over-time data. Evidence for convergent and
      discriminant validity of the self-report measure of appraisals was found with
      scores derived from children's open-ended descriptions of their appraisals. Cross
      sectional structural equation models found significant paths between negative
      appraisal and psychological symptoms, over and above the direct effects of the
      traditional life event measure of stress. Structural equation modeling of
      longitudinal (5.5 months) data found a significant path from Time 1 appraisal to
      Time 2 anxiety for the older children.

PMID- 9022237
TI  - Adolescent paid labor and relationships with parents: early work-family linkages.
AB  - Earnings represent an important mechanism by which changes occur in the
      adolescent-parent relationship. The present study examines adolescent earnings
      and multiple dimensions of relationships with parents by drawing on 4 waves of
      data from the Iowa Youth and Families project. Dynamic models based on the
      multiple perspectives of adolescent and parent are estimated with hierarchical
      equations. Between the seventh and tenth grades, rural adolescent earnings and
      nonleisure spending are related to time spent with the family, less parental
      monitoring, and more sharing of advice within the family. Earnings and nonleisure
      spending have positive associations with the affective quality of the adolescent
      parent relationship. These results are discussed in terms of the multifaceted
      dimensions of adolescent work experiences and their implications for the life
      course.

PMID- 9022238
TI  - Interactions between family environment and friendship and associations with self
      perceived well-being during early adolescence.
AB  - Using a sample of 138 early adolescents and their parents, we examined the
      hypothesis that family and friendship measures would moderate each other's
      associations with measures of children's perceptions of their adjustment and well
      being. Family environment was assessed by asking parents to complete the Family
      Adaptability and Cohesion Scale II. A sociometric nomination procedure and the
      Friendship Quality Scale were completed by the subjects as assessments of
      reciprocity and quality in their best friendship relations. The Perceived
      Competence Scale for Children was used to assess children's adjustment. Stronger
      associations were observed between the family measures and the adjustment
      measures in children without a close friendship than in children with such a
      relationship. Also, friendship was more strongly linked to outcome measures for
      children from low adaptive and low cohesive families than for children in more
      adaptive and cohesive families. These findings indicate that experiences in the
      family and friendship domains interact in their associations with children's
      impressions of their adjustment during early adolescence.

PMID- 9022239
TI  - Reciprocal negative affect in parent-child interactions and children's peer
      competency.
AB  - The relationship between preschool children's peer competency and the exchange of
      reciprocal negative affect displays during physical play with parents was
      examined. Teacher ratings of children's peer competency were obtained from
      children's preschools. Parents and children (41 families) were observed during a
      physical play paradigm called "the hand game" which permitted physically
      stimulating play, yet which also permitted clear recording of participants'
      facial expressions. Interactions were coded second by second for 8 min using a
      system of 12 mutually exclusive and exhaustive codes to categorize the affect
      displayed by participants. Fathers who typically responded to their children's
      negative affect displays with negative affect of their own had children who
      shared less, were more aggressive, and avoided others. Implications of the
      findings for theories of family-peer relationships are discussed.

PMID- 9022240
TI  - Parents' reactions to children's negative emotions: relations to children's
      social competence and comforting behavior.
AB  - The purpose of this study was to examine the relations of mothers' and fathers'
      reported emotion-related practices to parents' and teachers' reports of third- to
      sixth-grade children's social skills, popularity, and coping, as well as the
      quantity and quality of children's comforting of an infant. Mothers' problem
      focused reactions tended to be positively associated with children's social
      functioning and coping, whereas maternal minimizing reactions tended to be linked
      to lower levels of social competence and high levels of avoidant coping. There
      were few findings for fathers' reactions, although fathers reported fewer problem
      focused reactions with socially competent, in contrast to less competent,
      daughters. Emotion-focused and problem-focused maternal reactions, as well as
      encouragement of the expression of emotion, were associated with boys' children's
      comforting behavior, although a moderate level of maternal encouragement of the
      expression of emotion was associated with quality of girls' comforting.

PMID- 9022241
TI  - Behavioral, affective, and social correlates of involvement in cross-sex
      friendship in elementary school.
AB  - The purpose of this study was to compare children with and without cross-sex
      friends on measures of social and cognitive competence, endorsement of sex-role
      stereotypes, and family composition. Subjects were 723 third and fourth graders
      (377 girls, 346 boys) from diverse socioeconomic backgrounds; 35% were African
      American. Measures included sociometric assessments of peer acceptance,
      friendship, and behavioral reputation, as well as self-reports of perceived self
      competence and endorsement of sex-role stereotypes. In addition, teachers
      completed ratings of children's social and cognitive competence. In all, 92
      children, about 14% of the sample, had one or more reciprocal opposite-sex
      friends; for 21 of these children, their cross-sex friendships were their primary
      or only friendships. African American children were more likely than European
      American children to have opposite-sex friends. Involvement in cross-sex
      friendships was unrelated to the gender make-up of the classroom but was related
      to family structure. Comparisons of the children who had primarily or only cross
      sex friends to matched groups of children who had only same-sex friends and to
      children who had cross-sex friends secondarily to same-sex ones revealed a number
      of differences between the groups in social competence and relationships with
      peers. Overall, children with primarily opposite-sex friends had poorer social
      skills than other children with friends, although they were less stereotyped
      about sex roles than other children, and were better adjusted than children with
      no friends on most measures. In contrast, children involved in opposite-sex
      friendship secondarily to same-sex friendship were as well adjusted socially as
      children with only same-sex friendships. These results suggest that children with
      cross-sex friends differ among themselves, depending on the primacy of the cross
      sex relationship.

PMID- 9022242
TI  - Effects of friendship and gender on peer group entry.
AB  - Effects of hosts' conflicting motives (to win a game vs. to be a good friend) on
      peer group entry processes and outcomes were examined. Subjects were 68 triads
      (35 female) of 10-12-year-old predominantly White children. Two host friends
      played a game for a large prize that was forfeited for a smaller prize if the
      guest (a friend or nonfriend of both hosts) was included. Hosts admitted guest
      friends more often than nonfriends (44% vs. 26%), suggesting that friendship
      norms prescribe self-sacrifice. Hosts behaved similarly with guest friends and
      nonfriends, but guest friends were more active than nonfriends, reflecting
      freedom derived from friendship security. Female hosts admitted guests more often
      than male hosts (51% vs. 21%), consistent with communal and agentic gender role
      prescriptions for girls and boys, respectively. Results suggest that hosts'
      friendship obligations and psychological orientation affect their response to a
      newcomer in a group entry situation.

PMID- 9022243
TI  - The role of overt aggression, relational aggression, and prosocial behavior in
      the prediction of children's future social adjustment.
AB  - 2 limitations of past research on social adjustment were addressed: (1) the
      tendency to focus on forms of aggression that are typical of boys (e.g., overt
      aggression) and to neglect forms that are more typical of girls (e.g., relational
      aggression) and (2) the tendency to study negative behaviors (e.g., aggression),
      to the exclusion of positive behaviors (e.g., prosocial acts). Using a
      longitudinal design (n = 245; third- through sixth-grade children, 9-12 years
      old), assessments of children's relational aggression, overt aggression,
      prosocial behavior, and social adjustment were obtained at 3 points during the
      academic year. Findings showed that, as has been demonstrated in past research
      for overt aggression, individual differences in relational aggression were
      relatively stable over time. Additionally, relational aggression contributed
      uniquely to the prediction of future social maladjustment, beyond that predicted
      by overt aggression. Finally, prosocial behavior contributed unique information
      (beyond that provided by overt and relational aggression) to the prediction of
      future social adjustment.

PMID- 9022244
TI  - Relational aggression, overt aggression, and friendship.
AB  - This study (n = 315 9-12-year-olds) was conducted to assess whether the social
      problems that relationally and overtly aggressive children typically experience
      in the peer group context are also exhibited in the dyadic, friendship context.
      The qualities of children's friendships (e.g., levels of intimacy) and of the
      importance of those qualities (e.g., the importance of intimacy) were assessed
      with self-report instruments adapted from past research. Results indicated that
      the friendships of relationally aggressive children were characterized by
      relatively high levels of intimacy, exclusivity/jealousy, and relational
      aggression within the friendship context. In contrast, the friendships of overtly
      aggressive children were characterized by engaging together in aggressive acts
      toward those outside the friendship. In addition, overtly aggressive children
      placed relatively high importance on these coalitional acts and on companionship
      with their friends. Implications for our understanding of aggressive children and
      for our knowledge of children's friendships are discussed.

PMID- 9022245
TI  - Coping socialization in middle childhood: tests of maternal and paternal
      influences.
AB  - A theoretical model of parental socialization of children's coping behavior is
      described and tested with 310 elementary school children (M age = 10.5 years).
      Mothers and fathers reported on the coping suggestions they made to their
      children, their own coping strategies, and their perceptions of the family
      environment. Children reported on their relationships with their parents and on
      their usual coping behavior. Children's coping efforts were associated with
      family environment, the quality of the parent-child relationship, parent's own
      coping, and parent coping suggestions, though these relationships differed by
      gender and were quite specific. Maternal data were more strongly associated with
      children's coping than paternal data, and active and support coping were
      predicted more successfully than avoidance strategies. Analyses supported a model
      of direct, rather than mediated, effects on children's coping. There was modest
      support for the interactive effects of maternal coaching and modeling on girls'
      active coping and boys' avoidant coping.

PMID- 9022246
TI  - Openness in adoption and the level of child participation.
AB  - There is great controversy regarding the impact of openness in adoption,
      especially the impact of such an arrangement on adopted children. Three
      indicators of the level of child participation in the openness arrangement were
      examined: (a) level of openness reported by adoptive parents, (b) level of
      information adopted children reported having about their birthparents, and (c)
      whether adoptive parents have withheld any pertinent information gained through
      communication with the birthmother from the adopted child. 171 children (90
      males, 81 females; mean age = 7.99) wee studied to assess how that participation
      influenced their conceptual understanding of what adoption means, general self
      worth, satisfaction with level of openness, and curiosity about birthparents.
      Overall it does not appear that providing information about a child's
      birthparents will confuse the child about the meaning of adoption or lower the
      child's self-esteem, but neither will it move them to levels of understanding
      that are beyond their cognitive capabilities to reach.

PMID- 9022247
TI  - School leaving: a longitudinal perspective including neighborhood effects.
AB  - Using 1970 and 1980 census data from 202 tracts in the Chicago metropolitan
      region, we examine whether neighborhoods influence the likelihood of high school
      graduation for a cohort of African-American children followed from 1966 to 1993.
      Neighborhood-level variables included percent living below poverty and percent in
      white collar occupations. We test for the possible direct, indirect, and
      interactive effects of these neighborhood indicators on the likelihood of school
      dropout. Our examination found the advantage of living in a neighborhood
      characterized by a high percentage of residents who work in white-collar
      occupations. Male adolescents who lived in a middle-class neighborhood were more
      likely to graduate from high school, even with family background, early school
      performance, adolescent family supervision, and adolescent marijuana use
      controlled. These findings are consistent with findings from three other studies.
      However, living in a poverty census tract did not seem to influence the
      likelihood of high school graduation or school leaving over and above the impact
      of family and individual characteristics. There also were no neighborhood effects
      for females.

PMID- 9022248
TI  - Patterns of change in early childhood aggressive-disruptive behavior: gender
      differences in predictions from early coercive and affectionate mother-child
      interactions.
AB  - The present study focused on mother-child interaction predictors of initial
      levels and change in child aggressive and disruptive behavior at school from
      kindergarten to third grade. Aggression-disruption was measured via annual
      reports from teachers and peers. Ordinary least-squares regression was used to
      identify 8 separate child aggression trajectories, 4 for each gender: high
      initial levels with increases in aggression, high initial levels with decrease in
      aggression, low initial levels with increases in aggression, and low initial
      levels with decreases in aggression. Mother-child interaction measures of
      coercion and nonaffection collected prior to kindergarten were predictive of
      initial levels of aggression-disruption in kindergarten in both boys and girls.
      However, boys and girls differed in how coercion and nonaffection predicted
      change in aggression-disruption across elementary school years. For boys, high
      coercion and nonaffection were particularly associated with the high-increasing
      aggression trajectory, but for girls, high levels of coercion and nonaffection
      were associated with the high-decreasing-aggression trajectory. This difference
      is discussed in the context of Patterson et al.'s coercion training theory, and
      the need for gender-specific theories of aggressive development is noted.

PMID- 9022249
TI  - Quality of care at school-aged child-care programs: regulatable features,
      observed experiences, child perspectives, and parent perspectives.
AB  - This study investigates children's experiences at 30 school-aged child-care
      (SACC) programs. Regulatable features such as total enrollment, child-staff
      ratio, and staff education were assessed via director report. Observers recorded
      positive/neutral and negative staff-child interactions, and rated programs in
      terms of flexibility and age appropriateness. Negative staff-child interactions
      were more frequent when child-staff ratios were larger and when staff had less
      formal education. The presence of a greater number of different types of program
      activities was associated with staff having more frequent positive interactions
      with children and with observers rating programs as flexible and age appropriate.
      These regulatable and observed features were examined in relation to children's
      (N = 180) and parents' (N = 152) perceptions of program psychosocial climate.
      Children's reports of overall climate, emotional support from staff, and
      autonomy/privacy provisions were predicted by program features. Children reported
      poorer program climate when programs had larger enrollments and when observers
      recorded more frequent negative staff-child interactions. Children had more
      positive program perceptions when programs offered a greater variety of
      activities. Children's reports of program climate in addition to observed child
      staff ratios were associated with parental perceptions of the programs. Parents
      had more positive perceptions when child-adult ratios were smaller and when their
      children reported more positive climates. This study suggests a convergence
      between observer, child, and parent about factors contributing to quality of
      after-school programs.

PMID- 9022250
TI  - Culture and class influences on Anglo and Puerto Rican mothers' beliefs regarding
      long-term socialization goals and child behavior.
AB  - These 2 studies examine culture and socioeconomic status as simultaneous possible
      sources for group differences in mothers' beliefs regarding desirable and
      undesirable long-term socialization goals and child behavior. In Study 1, 100
      mothers of young toddlers aged 12-24 months from 5 sociocultural groups
      participated: middle- and lower-class Anglo, middle- and lower-class island
      Puerto Rican, and lower-class migrant Puerto Rican. Results indicate that culture
      and socioeconomic status contribute independently to group differences, but that
      cultural effects appear to be stronger. Study 2 examined cultural differences in
      perceptions of behaviors using middle-class Anglo and Puerto Rican mothers only.
      The findings support those of Study 1, suggesting that Anglo and Puerto Rican
      mothers place differential value on the constructs of Self-Maximization and
      Proper Demeanor, even when socioeconomic status is controlled for. The findings
      of these studies have important implications for the culturally sensitive study
      of the relation between parental beliefs and behaviors.

PMID- 9022251
TI  - Japanese and United States preschool children's responses to conflict and
      distress.
AB  - Japanese and U.S. preschool children's responses to hypothetical interpersonal
      dilemmas were examined as a function of culture, gender, and maternal child
      rearing values. U.S. children showed more anger, more aggressive behavior and
      language, and underregulation of emotion than Japanese children, across different
      contexts of assessment. Children from the 2 cultures appeared more similar on
      prosocial and avoidant patterns, though in some contexts U.S. children also
      showed more prosocial themes. Girls from both cultures expressed more prosocial
      themes and sometimes more anger than boys. Maternal encouragement of children's
      emotional expressivity was correlated with anger and aggression in children. It
      was more characteristic of U.S. than Japanese mothers, while emphasis on
      psychological discipline (reasoning; guilt and anxiety induction) was more
      characteristic of Japanese than U.S. mothers. The relevance of a conceptual
      framework that focuses on differences in Eastern and Western cultures in self
      construals regarding independence and interdependence is considered.

PMID- 9022252
TI  - The internal working model of the self, attachment, and competence in five-year
      olds.
AB  - The present studies examine some of the correlates of the self in the lives of
      young children. In Study 1, the connection is tested between young children's
      internal working model of self and their competence, social acceptance,
      behavioral adjustment, and behavioral manifestations of self-esteem. Ninety-five
      kindergartners aged between 51 and 76 months (Mage = 5 years, 3 months)
      participated in the study. An adapted version of the Puppet Interview was used to
      assess the representation of self. Affective quality (positiveness) of self and
      openness to admit imperfections were rated independently. Results show
      significant and positive relations of the positiveness of self with competence
      and social acceptance, with behavioral adjustment to school, and with behavioral
      manifestations of self-esteem, all rated by the teacher. In Study 2, Bowlby's
      assumption was tested that the working model of self is closely intertwined with
      the working model of attachment to mother. Subjects were 50 children aged between
      55 months and 75 months (Mage = 5 years, 5 months). The working model of child
      mother attachment was assessed through an Attachment Story Completion Task. The
      working model of self was measured via the Puppet Interview. Results show a
      positive and strong connection between the security of the child-mother
      attachment representation and the positiveness of self. The results of the two
      studies contribute to the validation of the adapted Puppet Interview. The Puppet
      Interview seems to be a promising instrument for assessing the representation of
      self in young children.

PMID- 9022254
TI  - Individual differences, daily fluctuations, and developmental changes in amounts
      of infant waking, fussing, crying, feeding, and sleeping.
AB  - Measures of the amounts of time infants spent asleep, awake-content, feeding,
      fussing, and crying at 2, 6, 12, and 40 weeks of age were examined using
      multilevel analysis. This method enables the proportion of the variance in each
      behavior due to individual differences to be compared to the proportion due to
      age changes (development) and to day-to-day fluctuations at each age in the same
      infants. Day-to-day fluctuations were found to account for the largest proportion
      of the variance in amounts of sleeping, fussing, and crying (between 44% and
      53%), testifying to the importance of instability in these behaviors as a
      characteristic of infancy. Against this background, both development and
      individual differences explained substantial proportions of the variance, with a
      somewhat different picture in each area of behavior. Amounts of waking and
      feeding were mainly accounted for by development, and no evidence of enduring
      individual differences was found. For sleeping, development and individual
      difference each contributed approximately a quarter of the variance, and the
      amounts infants slept remained moderately stable from 6 weeks to 9 months of age.
      Crying decreased linearly with age, with development accounting for 38% and
      individual difference 15% of the variance. Fussing proved a more stable
      characteristic than crying, and "high fussers" at 6 weeks of age were
      particularly likely to retain this characteristic at 9 months, whereas amount of
      crying in the first 3 months did not predict 9-month behavior. The study's
      clinical, conceptual, and methodological implications are discussed.

PMID- 9022253
TI  - The impact of postnatal depression and associated adversity on early mother
      infant interactions and later infant outcome.
AB  - The impact of maternal depression and adversity on mother-infant face-to-face
      interactions at 2 months, and on subsequent infant cognitive development and
      attachment, was examined in a low-risk sample of primiparous women and their
      infants. The severe disturbances in mother-infant engagement characteristic of
      depressed groups in disadvantaged populations were not evident in the context of
      postpartum mood disorder in the present study. However, compared to well women,
      depressed mothers were less sensitively attuned to their infants, and were less
      affirming and more negating of infant experience. Similar difficulties in
      maternal interactions were also evident in the context of social and personal
      adversity. Disturbances in early mother-infant interactions were found to be
      predictive of poorer infant cognitive outcome at 18 months. Infant attachment, by
      contrast, was not related to the quality of 2-month interactions, but was
      significantly associated with the occurrence of adversity, as well as postpartum
      depression.

PMID- 9022255
TI  - Prenatal maternal reactivity to infant cries predicts postnatal perceptions of
      infant temperament and marriage appraisal.
AB  - In a sample of 60 primiparous women, cardiac response and ratings of subjective
      aversiveness to recordings of unfamiliar infant cries were studied at 32 weeks'
      gestation. Regression analyses were used to examine relations between cardiac
      acceleration and subjective aversiveness and 3 groups of postnatal dependent
      variables: perception of infant temperament, the mother's emotional state, and
      her appraisal of her marriage. Mothers who prenatally rated the cry recordings as
      more aversive postnatally described their 3-month-old infants as more
      fussy/difficult and unpredictable. With statistical control for prenatal
      variation on the emotional state and marital outcome measures, cardiac
      acceleration predicted later marital quality. Women who showed greater cardiac
      acceleration to the cries described their postnatal marital relationships more
      negatively.

PMID- 9022256
TI  - Fetal neurobehavioral development.
AB  - The ontogeny of fetal autonomic, motoric, state, and interactive functioning was
      investigated longitudinally in a sample of 31 healthy fetuses from 20 weeks
      through term. Fetal heart rate and movement data were collected during 50 min of
      doppler-based fetal monitoring at 6 gestational ages. Measures of fetal heart
      rate and variability, activity level and vigor, behavioral state, and reactivity
      were derived from these digitized data. Weighted least squares analyses were
      conducted to model the developmental patterns and to examine the role of maternal
      and fetal covariates. With advancing gestation, fetuses displayed slower heart
      rate, increased heart rate variability, reduced but more vigorous motor behavior,
      coalescence of heart rate and movement patterns into distinct behavioral states,
      and increasing cardiac responsivity to stimulation. Male fetuses were more active
      than female fetuses, and greater maternal stress appraisal was associated with
      reduced fetal heart variability. An apparent period of neurobehavioral transition
      exists between 28 and 32 weeks. Fetal research methods are evaluated.

PMID- 9022257
TI  - Fetal antecedents of infant temperament.
AB  - This study established the emergence of stable individual differences in
      neurobehavioral functioning prior to birth and examined their relation to
      subsequent infant temperament. Fetal heart rate and movement were recorded
      longitudinally for 31 fetuses at 6 gestational ages beginning at 20 weeks'
      gestation. Maternally reported temperament data were collected at 3 and 6 months.
      Moderate stability in all measures except reactivity was apparent at some time
      before birth. By 36 weeks, fetal neurobehavior accounted for between 22% and 60%
      of the variance in prediction of temperament scores. In general, more active
      fetuses were more difficult, unpredictable, unadaptable, and active infants.
      Higher fetal heart rate was associated with lower emotional tone, activity level,
      and predictability. We conclude that features of fetal neurobehavior provide the
      basis for individual differences in reactivity and regulation in infancy.

PMID- 9022258
TI  - Discriminant validity of the adult attachment interview.
AB  - The Adult Attachment Interview is a semi-structured interview developed to
      investigate adults' attachment representations. Subjects are asked to describe
      their parents as caregivers, explain these descriptions, describe how their
      parents typically responded to distress, and discuss their current relationships
      with their parents. They are also asked to describe any significant losses and/or
      instances of abuse during childhood. Scoring focuses on the accessibility of
      early experiences to memory and the coherence and plausibility of the subject's
      narrative. Discriminant validity is always an important issue with such measures
      because IQ and other cognitively loaded variables offer plausible alternative
      interpretations or represent important correlates that should be treated as
      covariates when the measure is used. In addition, complex, multifaceted
      interviews always pose the risk of assessing general social adjustment rather
      than a more narrowly defined construct. This study examines the discriminant
      validity of the AAI vis(-)a-vis intelligence, social desirability, discourse
      style, and general social adjustment in a sample of 53 native-English-speaking,
      married women with preschool children. They were assessed with the AAI, a written
      IQ test, the Social Adjustment Scale, the Employment Experience Interview
      (discourse style), and a measure of social desirability. There were modest but
      significant correlations with IQ scores and social adjustment. There was no
      relation between AAI classifications and discourse style or social desirability.
      These results substantially strengthen the case for interpreting the AAI as an
      attachment-related measure.

PMID- 9022259
TI  - A pattern classification procedure integrating the multivariate statistical
      analysis with neural networks.
AB  - A new procedure integrating multivariate statistical analysis with artificial
      neural networks (ANN) for complex pattern classification is proposed. Firstly, a
      specially designed statistical analysis algorithm called correlative component
      analysis (CCA) was used to identify the classification characteristics (CC) from
      original high-dimensional pattern information. These CC were then used as input
      data to the ANN for pattern classification. The proposed new procedure not only
      effectively decreased the dimensionality of original patterns, but also took
      advantage of the self-learning power of the ANN. Further, a typical example of
      classifying natural spearmint essence was employed to verify the effectiveness of
      the new pattern classification method. The study showed that this novel
      integrated procedure provides better results than those obtained using individual
      methods separately.

PMID- 9022260
TI  - Hormone-induced changes in cell shape: role of cytoskeletal proteins.
AB  - Shape is a characteristic phenotype for a given cell. It is affected by various
      physiological and pathological factors. Hormones, which are the chemical
      messengers affecting a wide range of biological phenomena, also alter cell
      morphology by influencing the expression and post-translational modifications of
      cytoskeletal proteins. The assembly/disassembly of cytoskeletal proteins and
      their interactions with intracellular components, the plasma membrane and
      extracellular matrix, is mainly responsible for determining cell shape. The role
      of hormones in the induction of altered cell shape due to changes in the
      cytoarchitecture in varied biological tissues under both in vivo and in vitro
      conditions, are discussed in this review.

PMID- 9022261
TI  - The possible role of yeast cell walls in modifying cellular response to
      chlorhexidine diacetate.
AB  - The relative porosity (RP) and thickness of cell walls of Saccharomyces
      cerevisiae depended upon the age of culture, the RP decreasing and the cell wall
      thickness increasing in older cultures. Chlorhexidine diacetate (CHA) produced
      cytological changes in S. cerevisiae cells, involving dense and granular
      cytoplasmic constituents, withdrawal of the interior from the cell wall and a
      general loss of the typical cellular organization. Cell wall mannan is unlikely
      to play a role in limiting the entry of CHA into yeast cells but changes in
      glucan composition, wall thickness and RP might be involved in determining the
      sensitivity of cells to the biguanide.

PMID- 9022262
TI  - Effect of granulocyte-macrophage colony stimulating factor and granulocyte colony
      stimulating factor on prolactin and adrenocorticotropic hormone secretion in
      rats: dose- and time-response in vivo studies.
AB  - The in vivo effect of granulocyte-macrophage colony stimulating factor (GM-CSF)
      and granulocyte colony stimulating factor (G-CSF) on the plasma levels of
      prolactin (PRL) and adrenocorticotropic hormone (ACTH) in rats were studied. The
      administration of 10 micrograms/kg G-CSF at 45 min (p < 0.05) and 90 min (p <
      0.01) or 10 micrograms/kg GM-CSF at 45 and 90 min (p < 0.01) stimulated the
      secretion of ACTH. Moreover, G-CSF administration only, in doses of 10
      micrograms/kg at 45 min (p < 0.05) and 90 min (p < 0.01) augmented PRL secretion
      into the blood. These experiments suggest that the human colony stimulating
      factors (GM-CSF and G-CSF) activate the anterior pituitary gland in vivo to ACTH
      secretion, but only G-CSF positively influenced PRL release in rats.

PMID- 9022263
TI  - Effect of plant extracts and systemic fungicide on the pineapple fruit-rotting
      fungus, Ceratocystis paradoxa.
AB  - Antifungal activities of extracts of sixteen plants were tested against
      Ceratocystis paradoxa which causes soft rot of pineapples. Xanthium strumarium
      was the most effective followed by Allium sativum. The effectiveness of various
      extracts against C. paradoxa was in the decreasing order of Meriandra
      bengalensis, Mentha piperita, Curcuma longa, Phlogacanthus thyrsiflorus, Toona
      ciliata, Vitex negundo, Azadirachta indica, Eupatorium birmanicum, Ocimum sanctum
      and Leucas aspera. Extracts of Cassia tora, Gynura cusimba, Calotropis gigantea
      and Ocimum canum showed poor fungitoxicity. Ethanol was suitable for extraction
      of the inhibitory substance from X. strumarium. Acetonitrile was highly toxic to
      this fungus. Millipore filter-sterilized extracts had a more inhibitory effect on
      the fungus than the autoclaved samples. Treatment of pineapple fruits infested
      with C. paradoxa by X. strumarium extract reduced the severity of the disease.

PMID- 9022264
TI  - Neutrophil activation in nickel sensitized subjects.
AB  - Conflicting results were obtained from the evaluation of nickel-mediated effects
      on immunoresponsiveness. A reduction of B cell polyclonal response, mixed
      lymphocyte reaction, T lymphocyte proliferation and natural killer cytotoxicity
      was evident following nickel salt exposure. On the contrary, an enhancement of
      cytokine release, T cell proliferative capacity and adhesion molecule expression
      was found in nickel sensitized donors. In addition, under different experimental
      conditions, respiratory burst induction and myeloperoxidase release by
      polymorphonuclear cells (PMN) in a group of individuals exhibiting nickel
      hypersensitivity were investigated. Results provide evidence that nickel allergic
      individuals displayed a significant increase of superoxide anion (O2-) generation
      by suspended PMN in comparison with similar cell suspensions from healthy donors,
      but this was not the case when adherent neutrophils were used as effector cells.
      PMN from nickel sensitized donors exhibited a significant enhancement of hydrogen
      peroxide (H2O2) and myeloperoxidase release. The results imply the occurrence of
      neutrophil activation in nickel hypersensitivity, which in turn may be
      responsible for the low frequency of life-threatening infections in these
      subjects.

PMID- 9022265
TI  - Investigation on the taxonomic status of Steganacarus magnus and Steganacarus
      anomalus (Acari:Oribatida) using mitochondrial DNA sequences.
AB  - To test the previously suggested synonymization of S. anomalus with the older S.
      magnus, a fragment of the mitochondrial COI gene was amplified via the polymerase
      chain reaction and sequenced. The sequence variation was examined in a total of
      327 base pairs for four steganacarid mite populations, two of which belong to S.
      anomalus, one to S. magnus and one to S. hirsutus. The sequence variation
      suggests that S. magnus and S. anomalus are not distinct species and that the
      population from Fioreta (Siena) is more similar to that from Apulia than to the
      nearer population from the Apuan Alps. The results show the usefulness of this
      molecular approach as a tool for determining taxonomic status and for suggesting
      faunistic movements in the past millions of years.

PMID- 9022266
TI  - Survival of six species of African ticks in relation to saturation deficits.
AB  - The survival of unfed males and females of six species of African ticks was
      monitored at five different saturation deficits at constant temperature (25
      degrees C). The survivorship curves for each species comprised a pre-mortality
      period, prior to when ticks started to die and a mortality period corresponding
      to a rapid increase in the mortality rate. Longevity was defined as pre-mortality
      plus mortality. A negative correlation between the longevity of the ticks and the
      saturation deficits was found with ticks surviving longer at lower deficits. The
      survival of males and females was similar. At low saturation deficits (2-4 mmHg)
      Amblyomma hebraeum survived the longest periods (74 weeks). Some correlation was
      found between the tick survival under dehydrating conditions and habitat
      associations. Rhipicephalus appendiculatus and Haemaphysalis leachii, the most
      mesic in distribution, had the shortest longevity (21 and 13 weeks, respectively)
      at high saturation deficits (7-21 mmHg). Hyalomma marginatum rufipes, the most
      xerophilic in distribution, had the longest survival (39.3 +/- 10.5 weeks) at
      high saturation deficits. Other factors apart from the adult survival should be
      taken into account when accounting for the tick distribution, in particular the
      tolerance of earlier developmental stages to desiccation.

PMID- 9022267
TI  - Vitellogenin concentrations in the haemolymph and ovaries of Ixodes scapularis
      ticks during vitellogenesis.
AB  - The vitellogenin and vitellin concentrations in the haemolymph and ovaries of
      Ixodes scapularis females were determined using a double sandwich enzyme-linked
      immunosorbent assay. The level of vitellogenin in the haemolymph began to
      increase just prior to tick detachment from the host and continued to increase
      until 2 days after detachment. There was a slight decrease in the vitellogenin
      level 4 days after detachment, but a second peak was observed approximately 5
      days after oviposition. Subsequent to oviposition, the vitellogenin levels in the
      haemolymph quickly decreased. The concentration of vitellogenin in the haemolymph
      ranged from 1.55 to 11.48 micrograms microliters-1 during the period after
      dropping from the host through oviposition. The concentration of vitellin in the
      ovaries began to increase as the female began rapid engorgement (0.03 mg per
      female) and declined after oviposition (0.1 mg per female).

PMID- 9022268
TI  - Dynamics of Borrelia burgdorferi infection in nymphal Ixodes ricinus ticks during
      feeding.
AB  - We report the sequential development events of Borrelia burgdorferi in
      histological sections of Ixodes ricinus nymphs before, during and after feeding.
      During the blood meal a decrease of approximately 50% in the number of infected
      ticks was recorded (eight out of 76, 11%) in comparison with the infection rate
      of unfed ticks (12 out of 56, 21%). Spirochetes were detected in tick salivary
      glands only after 2 days of attachment. From day 3 until drop-off, the number of
      infected ticks increased to 31% (15 out of 49). A quadratic logistic regression
      analysis showed that the variation in the number of infected ticks was
      significant, but only during the blood meal. The drop in the percentage of
      infected ticks during the first hours following attachment to the host is
      explained by our observation of spirochetes in the faces of the ticks. The
      increase in the infection rate of replete ticks may be due to an uptake of
      spirochetes from the host skin at the feeding site.

PMID- 9022269
TI  - Inheritance of weight in Rhipicephalus appendiculatus ticks (Acari:Ixodidae) in
      the laboratory.
AB  - A selection of the 10% lightest and 10% heaviest males and females of a
      population of individually weighed Rhipicephalus appendiculatus Neumann adults
      was made in two experiments. The offspring of homologous pairs were followed
      until the next adult stage (light x light, control x control and heavy x heavy).
      The engorged nymphal weights, unfed adult weights, engorged female weights of the
      parents, egg mass weights, egg weights, larval scutal lengths, engorged larval
      weights, unfed nymphal weights, engorged nymphal weights and adult weights of the
      progeny were determined. No significant differences could be demonstrated between
      the two lines for egg weight, larval scutal length, engorged larval weight and
      unfed nymphal weight. Significant differences were found between the egg masses,
      engorged nymphal weights and adult weights of the two lines. The heritability
      coefficients of body weight determined from adult to adult were 0.14 and 0.10,
      respectively, during the first and second experiments. Considering females and
      males separately, the coefficients were 0.10 and 0.18 during the first experiment
      and 0.12 and 0.09 during the repeat experiment respectively.

PMID- 9022270
TI  - Identification of human skin from a tissue fragment by detection of squamous cell
      carcinoma-related antigen using an enzyme immunoassay.
AB  - A new method of identifying human skin from a tissue fragment by detection of
      squamous cell carcinoma-related (SCC) antigen, using an enzyme immunoassay, was
      developed. When an extract was prepared from 0.1 g human skin homogenized with 1
      ml of phosphate buffered saline, this method was able to detect SCC antigen in
      extracts diluted 10(2)-fold. There was no difference in the detection limit
      between individuals. Species specificity was good, and there was no cross
      reaction observed with skins from animals. Our method could also discriminate
      between skin and other organs or tissues, except for esophagus and lung. A
      practical case to which this method was applied is presented.

PMID- 9022271
TI  - Paternity testing by the detection of D1S80 VNTR using fluorescence image
      analyzer (Dualcolour system).
AB  - An improved method for DNA polymorphism typing of D1S80 VNTR locus and its
      application to paternity testing are described. For accurate estimation of the
      length of polymorphic DNA fragments, the size marker was labeled with
      fluorescence different from that of PCR primers, and co-electrophoresed as an
      internal standard. The dualcolour system of fluorescence image analyzer was used
      to detect the fragments and determine their size. This internal marker method
      could successfully overcome the problems of band pattern distortion and tailing,
      besides it allows easy and accurate interpretation of the DNA types. Our results
      indicate that the internal marker method is much more accurate than the method of
      using size marker in gel, even with the presence of distortion or tailing of the
      band patterns. Family studies applying this method showed complete agreement
      between the observed and predicted types.

PMID- 9022272
TI  - Bone-dust in autopsies: reduction of spreading.
AB  - During autopsies, an open oscillating saw produces large quantities of respirable
      bone-dust, which is able to carry microbes over several metres. Experiments were
      done using a modified (open) undulation saw (spray tube to moisten the saw-blade
      with water). Saw-dust was asservated with culture media. Colonies were identified
      macroscopically. Microbes in the air were quantified (per unit of time). A
      remarkable reduction of saw-dust is done by an integrated spray tube using water.
      There remains a contamination at the head of the autopsy table in the level of
      the table top. We found a complete decontamination 150 cm above the floor. No
      spreading of particles carrying microbes was seen over distances of more than 1.5
      m. The risk of an airborne infection is minimal when using a manual saw (absence
      of grinding-dust). The modified type of an 'oscillating saw with a spray-tube'
      may be considered a practicable compromise between a manual saw and an
      unprotected undulation saw. It is necessary to complete the precautions against
      airborne infections by breath masks and safety-goggles.

PMID- 9022273
TI  - Mesh-sided cots--yet another potentially dangerous infant sleeping environment.
AB  - Two cases of accidental asphyxia involving an 11.5 month old boy and a 3.5 month
      old boy who each died after being trapped between the elastic mesh side of their
      cots and the cot mattress are reported. In both cases the original cot mattress
      has either been replaced or augmented by a less well fitting, thicker mattress.
      Particular problems that exist with these type of mesh sided cots are the
      potential for considerable stretching of the side of the cot admitting the
      relatively larger, poorly supported infant head, with elastic recoil of the mesh
      holding the head in potentially dangerous positions. To help determine whether
      accidental asphyxia has occurred, death scene examination in cases of sudden
      infant death during sleep should include reconstruction of the position of the
      body in the cot or bed, with careful examination of the structure of the cot/bed.

PMID- 9022274
TI  - Distribution of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4
      methylenedioxyamphetamine (MDA) stereoisomers in a fatal poisoning.
AB  - This communication presents the quantitation and differential distribution of the
      enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its physiologically
      active metabolite 3,4-methylenedioxyamphetamine (MDA) in a fatal poisoning
      following insufflation of MDMA, cocaine and heroin. Animal studies have
      demonstrated the stereoselective pharmacokinetics and neurotoxicity of these
      compounds; however, enantiomeric distributions have not been reported in humans.
      Quantitation of MDMA and MDA enantiomer was by gas chromatography/mass
      spectrometry (GC/MS) following chiral derivatization with N-trifluoroacetyl-L
      triproyl chloride (LTPC). The decedents' blood concentration of S(+)-MDMA was
      slightly less than that of R(-)-MDMA (1.3 vs. 1.6 mg/l, respectively), while the
      S(+)- and R(-)-MDA blood concentrations were identical (0.8 mg/l). Both primary
      routes of excretion, bile and urine, had greater concentrations of R(-)-MDMA than
      the S(+) isomer. These fluids also contained twice the concentration of S(+)-MDA
      than the R(-)-isomer. These data indicate that S(+)-MDMA is metabolized and
      eliminated faster than R(-)-MDMA. The results appear to support the findings in
      animals regarding stereoselective metabolism of MDMA.

PMID- 9022275
TI  - Outer ear temperature and time of death.
AB  - From a research sample of 138 corpses, divided into four subgroups of ambient
      storage temperature (0-5 degrees C, 6-10 degrees C, 11-15 degrees C and 16-23
      degrees C) four linear regression formulae of actual versus estimated post-mortem
      interval were obtained ('interval' formulae) using a single outer ear temperature
      measurement on both sides. This method showed the best correlation coefficient
      among five other methods previously proposed for time of death determination
      (rectal temperature, vitreous K+, CSF K+, blood log NA+/K+ and log Cl-), however
      its results were less accurate than those obtained with a multivariate equation
      combining several of the above mentioned methods. Eventually an equation
      expressing time of death (TOD) as a function of outer ear temperature (OE T
      degrees) and ambient temperature was also established from the whole research
      sample ('global' formulae). On a different sample of 141 corpses the regression
      formulae ('interval' and 'global') for the outer ear temperature were compared to
      three methods based on a single rectal temperature measurement ('rule of thumb' 1
      and 2, Henssge nomogram) and therefore useful at the scene; the results of all
      methods were compared within the four subgroups of ambient temperature as well as
      in three subgroups of different post-mortem interval lengths (< 7 h, < 10 h, < 15
      h). In all cases the outer ear temperature formulae provided better results than
      the rectal temperature methods (especially Henssge nomogram and rule of thumb 1).
      Moreover they did not show any post-mortem plateau which was present in almost
      30% of cases when rectal temperature was measured in corpses kept at ambient
      temperature above 15 degrees C. Our results show that outer ear temperature
      measurement is the method which provides the best simplicity/quality ratio and
      should therefore be proposed for use at the scene when conditions are similar to
      those of our experiment (within buildings). A software equipped thermometer is
      required in order to use in each case the appropriate formula and confidence
      interval.

PMID- 9022276
TI  - Identification by frontal sinus pattern in forensic anthropology.
AB  - The authors report forensic cases from the literature, as well as two personal
      homicide cases, of identification through comparison of frontal sinus
      radiographs. A general discussion about identification using frontal sinus X-rays
      is presented, pointing out the reliability of the method, in reference to the
      uniqueness of the frontal sinus in humans, but also some difficulties, especially
      in reference to the distance, orientation and angle of the X-ray technique.

PMID- 9022277
TI  - Calponin.
AB  - Calponin is a troponin-T like protein purified from chicken gizzard smooth
      muscle. It binds to actin, myosin, Ca(2+)-binding proteins and tropomyosin and
      inhibits the actomyosin ATPase as well as the movement of actin filaments over
      myosin in vitro. These properties have led to the proposal that calponin may be
      involved in the Ca(2+)-dependent regulation of actin-myosin interaction and
      consequently of smooth muscle contraction. Calponin is localized in both the
      contractile and the cytoskeletal parts of the smooth muscle cell and may have a
      structural function in smooth muscle cells. It may also regulate the pool of free
      actin available for cytoskeleton organization. In vitro calponin function is
      modulated by its interaction with a Ca(2+)-binding protein and/or by its
      phosphorylation. This suggests that calponin may play an important role in signal
      transduction from the membrane receptor to the contractile proteins in smooth
      muscle.

PMID- 9022278
TI  - NADPH oxidase.
AB  - Superoxide is instrumental in the killing of microorganisms by phagocytic cells.
      It is generated by the NADPH oxidase system, a membrane-bound electron transport
      complex which pumps electrons from NADPH in the cytoplasm across the wall of the
      phagocytic vacuole to molecular oxygen. Superoxide deficiency results in the
      genetically inherited condition Chronic Granulomatous Disease (CGD), in which the
      patient is abnormally susceptible to infection. In recent years many of the
      underlying genetic defects in CGD have been identified and are providing
      important insights into the structure and mechanism of the NADPH oxidase complex.

PMID- 9022279
TI  - Molecular mechanisms of hemoglobin switching.
AB  - The developmental regulation of the human beta-globin cluster embodies all
      aspects of transcriptional control of eukaryotic genes. The cis-acting sequences
      within the cluster, distal regulatory regions and trans-acting factors all
      contribute to provide stringent temporal and tissue-specific expression. This
      review will examine the individual regulatory mechanisms which govern globin gene
      expression and highlight recent advances which expand our understanding of these
      dynamic interactions.

PMID- 9022280
TI  - Angiotensinogen: molecular biology, biochemistry and physiology.
AB  - Angiotensinogen is the only known substrate for the enzyme renin. Angiotensin II,
      the end product of the reaction, is an extremely potent vasoconstrictor and a
      major determinant of salt and water homeostasis. It is also a growth factor.
      Angiotensinogen has been identified as a non-inhibitory member of the serine
      proteinase inhibitor family. Although the most abundant source of plasma
      angiotensinogen is the liver, the use of Northern blotting and reverse
      transcriptase PCR techniques has confirmed angiotensinogen mRNA expression in a
      wide range of tissues, including the kidney, brain, vascular tissue, adrenal
      gland, placenta and leucocytes. The sequencing of the rat and human
      angiotensinogen genes has increased our understanding of this protein and its
      role in physiology and the pathogenesis of human disease. Early observations on
      the regulation of angiotensinogen are now explicable at the molecular level, with
      the identification of the core promoter, hormone and acute phase responsive
      elements and tissue-specific enhancers. The role of angiotensinogen in the
      aetiology of hypertensive disorders has been tested in transgenic animals, and in
      case-controlled genetic association and linkage studies. This review examines our
      current understanding of angiotensinogen, in the light of recent advances.

PMID- 9022281
TI  - Binding and internalization of the melanocyte stimulating hormone receptor ligand
      [Nle4, D-Phe7] alpha-MSH in B16 melanoma cells.
AB  - The current study aims to ascertain the fate of the melanocyte stimulating
      hormone (MSH) receptor and its ligand [Nle4, D-Phe7] alpha-MSH (NDP-MSH)
      following binding to murine B16 melanoma cells. Cells were incubated with [125I]
      NDP-MSH for up to 180 min and binding, internalization and degradation
      determined. Intracellular trafficking of the radiolabel was assessed using
      Percoll density gradient centrifugation of homogenized cells. Receptor down
      regulation and receptor mRNA levels were also measured over 96 hr after exposure
      to 1 microM ligand. NDP-MSH accumulation increased with time in a temperature
      dependent manner and was inhibited by excess peptide. The ligand was rapidly
      internalized and translocated to the lysosomal compartment where it was degraded.
      Internalization was accompanied by a loss or down-regulation of cell surface
      receptors, suggesting internalization of the NDP-MSH-receptor complex. No
      recycling of the receptors between the plasma membrane and intracellular
      compartments could be detected in this cell-line. Approximately 15% of the
      surface receptors were resistant to down-regulation, possibly indicating receptor
      heterogeneity. Down-regulation persisted for up to 96 hr and was accompanied by a
      decrease in MSH receptor mRNA levels 48 hr after treatment. However, before this
      time, transcript levels were the same in treated and control cells. In contrast
      to what was seen with NDP-MSH, cell surface receptors removed with trypsin were
      rapidly replaced. These results show that NDP-MSH not only induced MSH receptor
      internalization but also inhibited receptor turnover, resulting in a prolonged
      down-regulation. It is concluded that, in B16 cells, the MSH receptor undergoes
      ligand-dependent internalization, resulting in a prolonged down-regulation.

PMID- 9022282
TI  - Gastrin and gastrin receptor antagonists bind to both N- and C-terminal halves of
      the 78 kDa gastrin-binding protein.
AB  - A 78 kDa gastrin-binding protein (GBP) has previously been identified as the
      target of the anti-proliferative effects of non-selective gastrin/cholecystokinin
      receptor antagonists on colorectal carcinoma cell lines. The GBP was related in
      sequence to a family of fatty acid oxidation enzymes possessing enoyl CoA
      hydratase and 3-hydroxyacyl CoA dehydrogenase activity. This study aims to define
      the binding site for gastrin and gastrin antagonists in greater detail. The N-
      and C-terminal halves of the porcine GBP were expressed independently as
      glutathione S-transferase fusion proteins in E. coli. Affinities of gastrin and
      gastrin antagonists for the fusion proteins were measured by competition for 125I
      [Nle15]-gastrin binding in a covalent cross-linking assay. The N- and C-terminal
      fusion proteins bound gastrin with affinities of 9.9 +/- 6.1 and 71 +/- 48
      microM, respectively (n = 3). These values were 40-fold and 300-fold lower than
      the affinity of the full-length GBP for gastrin (0.23 +/- 0.15 microM). In
      contrast, the affinities of the N- and C-terminal halves for the antagonists
      proglumide (22 +/- 13 and 10 +/- 4 mM, respectively) and benzotript (350 +/- 90
      and 400 +/- 160 micro M, respectively) were similar to each other and to the
      affinities of proglumide and benzotript for the full-length GBP (5.1 +/- 3.6 mM
      and 200 +/- 120 microM, respectively). It is concluded that proglumide and
      benzotript bind independently to both the hydratase and dehydrogenase active
      sites of the GBP, while a single molecule of gastrin may bind simultaneously to
      both active sites. A model is proposed which is consistent with these data, and
      which will assist in the development of more potent and selective GBP
      antagonists.

PMID- 9022283
TI  - Overexpression and functional analysis of a mitogen-inducible nuclear GTPase
      activating protein, Spa-1.
AB  - The two Ras-related GTPases called Rap1 and Rsr1, which share 50% sequence
      identity with Ras GTPases are known to be activated by two distinct mammalian
      GAPs, i.e. cytosolic GAP3c of 55 kDa and membrane-bound GAP3m of 85 kDa. Recently
      we have cloned a gene encoding a 68 kDa (p68) protein product, which is
      associated with chromosomes during interphase. The N-terminal 190 amino acids
      share 43% sequence identity with the second half of the GTPase activating domain
      (residues 210-397) of GAP3m. The N-terminal fragment of 209 amino acids of Spa-1
      (called Span-N) was overproduced in E. coli as a glutathione S-transferase (GST)
      fusion protein and affinity purified. Rap1 and Rsr1 GTPase stimulatory activity
      of Spa-1 was tested and compared with GAP3m. Spa-1 preferentially stimulates Rsr1
      GTPase rather than Rap1 GTPase, while GAP3m has a preference for Rap1 GTPase.
      This suggests that although Spa-1 and GAP3m stimulate GTPase of Rap1 family
      members, they differ in affinity for them. By mutational analysis it was also
      found that amino acid residues 10-183 are enough for Rap GAP activity of Spa-1.

PMID- 9022284
TI  - Isolation and identification of porcine embryonic basic protein as a fragment of
      pregnancy-associated glycoprotein-2.
AB  - Between days 11 and 12 of gestation, the porcine conceptus undergoes a
      metamorphosis from a spherical blastocyst to an elongate thread-like form. During
      this process, the conceptus secretes a variety of products. One of these products
      is protein previously referred to as porcine embryonic basic protein (BP). This
      protein has been shown to be a major secreted product between days 13 and 18. In
      this study, we report a simple two-step procedure to isolate BP from day 15
      porcine conceptus conditioned medium, utilized ion-exchange chromatography and
      reverse-phase HPLC. Purified BP was subjected to Edman degradation amino-terminal
      sequencing and a 25 amino acid residue sequence was obtained. Comparing the N
      terminal sequence of BP to sequences in the GenBank database determined that BP
      shared amino acid homology with porcine pregnancy-associated glycoprotein-2 (PAG
      2). The region of identity corresponded to an internal site of PAG-2, suggesting
      BP was a proteolytic fragment of PAG-2. The purified protein was confirmed to be
      BP by Western blot using a previously characterized anti-BP antiserum. Also, the
      BP was immunolocalized with the trophectoderm of day 11 blastocysts. Staining
      intensity was diminished in spherical blastocysts compared to elongated
      blastocysts. Although the function of PAG-2 and its cleavage product BP are
      unknown, the large quantity produced by the porcine conceptus and its sequence
      conservation across species may indicate a necessary role in early pregnancy.

PMID- 9022285
TI  - Liver protein kinase C isozymes: properties and enzyme role in a vertebrate
      facultative anaerobe.
AB  - Protein kinase C was purified to homogeneity from liver of the anoxia-tolerant
      turtle (Trachemys scripta elegans). Two isozymes were present and were identified
      as PKC alpha and PKC beta by hydroxylapatite chromatography and cross-reaction
      with specific antibodies to the mammalian isozymes. Kinetic characterization of
      the isozymes showed that both required phospholipids and Ca2+ for activation and
      both were inhibited by low concentrations of PKC inhibitors. The PKC alpha was
      activated more strongly by phosphatidylinositol and lysophosphatidylinositol
      compared with PKC beta. Treatment with trypsin did not activate turtle PKC
      isozymes, but generated inactive PKC beta, whereas PKC alpha was resistant to
      inactivation. Anoxia exposure of turtles in vivo, via submergence in N2-gassed
      water at 7 degrees C, altered the activity and subcellular distribution of PKC in
      liver. After 1 hr of anoxic exposure at 7 degrees C, the activity of membrane
      bound PKC had increased by 2.4-fold and represented a translocation of 40% of PKC
      beta and more than 80% of PKC alpha from the cytosol to the membrane-associated
      fraction. With longer submergence, however, membrane-bound PKC activity was
      suppressed again. This two-phase response to anoxia by PKC suggests that an
      activation of PKC, through its translocation to the membrane, is important in
      mediating the initial metabolic responses to submergence, which include an
      activation of glycogenolysis during the hypoxia transition period. With sustained
      anoxia exposure, the subsequent reduction of PKC activity may be part of the
      overall mechanism of metabolic rate depression that allows endurance of prolonged
      anoxia.

PMID- 9022286
TI  - Purification and characterization of glutathione S-transferases of rat uterus.
AB  - Glutathione S-transferases (GSTs) provide protection to cells against
      electrophilic xenobiotics as well as lipid hydroperoxides and 4-hydroxynonenal
      generated during lipid peroxidation. The catalytic properties of the alpha class
      GSTs are well suited for detoxification of electrophilic products of lipid
      peroxidation. An immunologically distinct subgroup of the alpha class GST
      isozymes having high activity towards 4-hydroxynonenal has been recently
      identified in several mammalian tissues [Zimniak et al. (1994) J. Biol. Chem.
      269, 992-1000]. Since oxidative stress can exert deleterious effects during
      gestation, the present studies were performed to determine whether the rat
      homolog of this group of GSTs, rGST 8-8, is expressed in gravid rat uterus, where
      it may function as a defense mechanism against oxidative stress. GSTs were
      purified by GSH-affinity chromatography. Individual GST isozymes were separated
      by column isoelectric focusing and their immunologic identities were established
      using highly specific polyclonal antibodies in Western blot analysis. Their
      expression was quantified and kinetic properties were characterized. Rat uterus
      contained an alpha class GST (pI 9.8), a pi class GST (pI 8.1), two mu class GSTs
      (pI 6.7 and 6.2) and rGST 8-8. This result indicated that rGST subunits 1, 2, 3,
      4, 7 and 8 are present in rat uterus. The relative abundance of rGST 8-8 in the
      gravid rat uterus was found to be about three-fold higher as compared with that
      previously seen in rat liver. Higher relative abundance of rGST8-8 in gravid rat
      uterus suggests that it may play a protective role against the deleterious
      effects of lipid peroxidation during gestation.

PMID- 9022287
TI  - Potato lectin: a three-domain glycoprotein with novel hydroxyproline-containing
      sequences and sequence similarities to wheat-germ agglutinin.
AB  - Potato (Solanum tuberosum) tuber lectin is a chitin-binding, hydroxyproline-rich
      glycoprotein, which may be involved in the defence mechanism of the plant. We had
      previously obtained evidence that it consists of at least two very dissimilar
      domains. The aim was to use a combination of accurate determinations of molecular
      weight and protein sequencing to gain more accurate information on the domains.
      Accurate determinations of the molecular weight of the lectin by a MALDI mass
      spectrometer have shown that the subunit molecular weight is 65,500 (+/- 1100)
      and that of a totally deglycosylated sample is 31,250 (+/- 30). This means that
      the lectin is 52.3 (+/- 1)% carbohydrate with a considerable number of glycoforms
      being present. Partial sequences and other analyses are consistent with the
      existence of three distinct domains. These are: (1) an N-terminal region which is
      rich in proline but poor in hydroxyproline; (2) a glycosylated region with a
      glycosylated molecular weight of 45,300 (+/- 1100) and a deglycosylated molecular
      weight of 11,050 (+/- 50) which is extremely rich in glycosylated hydroxyproline
      residues with a similar sequence to extensins; and (3) a cystine-rich domain
      which has the sugar binding site shows partial conservation of a repeated motif
      common to many chitin-binding proteins of the hevin family including wheat-germ
      agglutinin. The closest similarity seems to be to the sequence of potato basic
      chitinase.

PMID- 9022288
TI  - Bone morphogenic protein-4.
AB  - Bone morphogenic protein-4 (BMP-4) is one of nine structurally related BMPs
      belonging to the transforming growth factor-beta (TGF-beta) superfamily of
      secreted proteins. Mature BMP-4 is a dimer that binds to a multimeric
      transmembrane receptor with serine/threonine kinase activity. Although discovered
      because it stimulates bone formation in adult mammals, BMP-4 has important roles
      as a signalling molecule in embryonic tissues, including the developing central
      and peripheral nervous system, musculature and skeleton. It participates in an
      ancient signalling pathway also found in insects and worms. Nevertheless, the
      main practical application of BMPs is for stimulating repair of bone, and their
      use in humans is currently being assessed.

PMID- 9022289
TI  - Glycation of collagen: the basis of its central role in the late complications of
      ageing and diabetes.
AB  - The most serious late complication of ageing and diabetes mellitus follow similar
      patterns in the dysfunction of retinal capillaries, renal tissue, and the
      cardiovascular system. The changes are accelerated in diabetic patients owing to
      hyerglycaemia and are the major cause of premature morbidity and mortality. These
      tissues and their optimal functioning are dependent on the integrity of their
      supporting framework of collagen. It is the modification of the properties by
      glycation that results in many of the damaging late complications. Initially
      glycation affects the interactions of collagen with cells and other matrix
      components, but the most damaging effects are caused by the formation of glucose
      mediated intermolecular cross-links. These cross-links decrease the critical
      flexibility and permeability of the tissues and reduce turnover. In contrast to
      the renal and retinal tissue, the cardiovascular system also contains a
      significant proportion of other fibrous connective tissue protein elastin, and
      its properties are similarly modified by glycation. The nature of these glycation
      cross-links is now being unravelled and this knowledge is crucial in any attempt
      to inhibit these deleterious glycation reactions.

PMID- 9022290
TI  - Identification of five hemoglobins in B6C3F1 mice by mass spectrometry and
      sequence analysis.
AB  - The aim of the work is to identify and characterize the hemoglobins found in
      B6C3F1 mice using mass spectrometry. The primary structures are compared to those
      reported for BALB/c mice. Individual hemoglobin chains were isolated by reverse
      phase high performance liquid chromatography (RP-HPLC). The molecular masses of
      the globins were determined using electrospray ionization (ESI) and matrix
      assisted laser desorption ionization (MALDI). The purified globin chains were
      enzymatically cleaved and the resulting peptides were separated by RP-HPLC. The
      chains were identified by N-terminal sequencing and mass spectrometry (MALDI).
      Selected peptides were analysed by Edman degradation. ESI analysis indicates that
      B6C3F1 mice have two alpha-globin chains (alpha-1 and alpha-2) and at least three
      beta-globin chains, beta-1, beta-2 and beta-3. This is one additional alpha- and
      one additional beta-globin chain than reported in the literature for BALB/c mice.
      Mass and sequence analysis of enzymatically generated peptides showed variations
      in the amino acid sequence in the alpha-1, alpha-2, beta-2 and beta-3 chains
      compared to the BALB/c mouse hemoglobins (alpha, beta (minor) and beta (major)).
      The study showed that mass spectrometry in combination with traditional protein
      chemistry is able to identify and locate minor protein sequence variations.

PMID- 9022291
TI  - Phorbol ester (12-O-tetradecanoylphorbol 13-acetate) prevents ornithine
      decarboxylase inhibition and apoptosis and L1210 leukemic cells exposed to TGF
      beta 1.
AB  - Previous studies have shown that growth suppression and apoptosis of leukemic
      cells exposed to TGF-beta 1 is associated with the inhibition of ornithine
      decarboxylase (ODC)--the key enzyme of polyamine pathway. The aim of the present
      study was to evaluate the influence of 12-O-tetradecanoylphorbol 13-acetate (TPA)
      -a potent ODC inducer on antiproliferative and apoptotic effects of TGF-beta 1 in
      L1210 leukemic cells. Cells were incubated in 2% FCS/RPMI-1640 medium,
      supplemented with TGF-beta 1 (2 ng/ml). TPA (100 ng/ml) or alpha
      difluoromethylornithine (DFMO) (5 mM). Cell proliferation, apoptosis and necrosis
      were evaluated using [methyl-3H] thymidine, electron microscopy, electrophoresis
      of DNA and trypan blue exclusion. Expression and activity of ODC were determined
      by RT-PCR and measurement of 14CO2 release from L-1-14C ornithine, respectively.
      TGF-beta 1 inhibited proliferation and induced apoptotic and necrotic cell death
      in L1210 leukemic cells. The above effects were associated with the inhibition of
      ODC expression and activity, measured 2 and 4 hr after TGF-beta 1 administration,
      respectively. The presence of DFMO, an irreversible inhibitor of ODC, led to
      apoptotic fragmentation of DNA, similar to that observed in TGF-beta 1-treated
      cultures. Administration of TPA simultaneously with TGF-beta 1 significantly
      reduced antiproliferative, apoptotic and necrotic effects of TGF-beta 1, and
      prevented its inhibitory action of ODC expression and activity. It is concluded
      that: down-regulation of ODC expression may be one of the early events associated
      with TGF-beta 1-evoked suppression of growth and apoptosis; ODC is involved in
      the mechanism of protective action of TPA on TGF-beta 1-related growth inhibition
      of L1210 leukemic cells.

PMID- 9022292
TI  - Specific stimulation of alpha 2-6 sialyltransferase activity by a novel cytosolic
      factor from rat colon.
AB  - A factor present in the 100,000 g supernatant from the homogenate of rat colon
      stimulated the activity of purified Gal beta 1-4GLcNAc alpha 2,6
      sialyltransferase [alpha 2-6ST(N)] from rat liver and alpha 2-6ST(N) from either
      liver microsomes or Golgi membrane. The stimulation of alpha 2-6ST(N) activity by
      the colon factor using protein acceptors was about four-fold and highly
      reproducible when the reaction product of the alpha 2-6ST(N) was assayed by
      either precipitation or affinity chromatography. In contrast, the colon factor
      did not stimulate the Gal beta 1-4GlcNAc alpha 2,3 sialyltransferase [alpha 2-3ST
      (N)], from rat jejunum microsomes or purified Gal beta 1-3GalNAc alpha 2,4
      sialyltransferase [alpha 2-3ST (O)] from porcine liver, of purified beta 1,4
      galactosyltransferase (GT) from bovine milk. In addition to rat colon, the 100,00
      g supernatant from the homogenates of rat brain and kidney also stimulated the
      alpha 2-6ST(N) activity. The stimulation of alpha 2-6ST(N) by the colon factor
      resulted in a decrease in the Km (by about two-fold) and an increase in Vmax
      (about 2- to 3-fold) for desialylated alpha 1 acid glycoprotein and CMP-[14C]N
      acetylneuraminic acid. The stimulation of alpha 2-6ST(N) activity by the colon
      factor was temperature dependent, protease sensitive and was inhibited by CTP,
      but did not need the presence of either metal ions or detergent. The cytosolic
      factor was partially purified by ion-exchange chromatography with the retention
      of the activator activity in the peaks containing low molecular weight proteins,
      but the activity was lost on attempts to further purification. A specific marked
      stimulation of the alpha 2-6ST(N) activity by cytosolic factors in certain
      tissues might suggest a physiological role for these factors in the regulation of
      alpha 2-5ST(N) activity.

PMID- 9022293
TI  - Chirality differences in amino acid retention and release from acid-extractable
      pool of cultured mammalian cells.
AB  - In previous work, no chiral differences were found between D and L enantiomers of
      Leu in their ability to displace one another from the acid-extractable pool in
      mammalian cells. Recent evidence suggested otherwise. Our aim is to examine
      whether, in physiological range, D-amino acids have an equivalent ability to
      displace L-amino acids from the acid-extractable pool of HeLa cells, and vice
      versa. In the Millimolar range, D-Leu and L-Leu have similar uptake and
      displacement properties with regard to the acid-extractable pool in HeLa cells,
      despite only the latter isomer being incorporated into protein. Below millimolar
      concentration however, a distinct difference was found in the displacement of
      tritium-labelled L-Leu from the pool by unlabelled D-Leu compared with unlabelled
      L-Leu. Thus, unlabelled L-Leu in the external medium at 10(-4) or 10(-5) M
      displaced and equivalent amount of label from the pool ad D-Leu introduced at a
      concentration approx. one order of magnitude higher, respectively. Reciprocal
      experiments, in which the acid-extractable pool was preloaded with 3H-D-Leu,
      confirmed this finding. The chirality difference was noted whether pool
      prelabelling was carried out at 37 or 0 degrees C; but in order to avoid the
      complications of active transport mechanisms, the competition work reported here
      was done at 0 degrees C. Similar chirality differences were observed with other
      hydrophobic amino acids, including His, Ile, and Phe, such as, preferential
      displacement by the L-Leu racemer compared with the D-Leu racemer below mM
      levels. This was also true for the D and L forms of the non-utilisable isomer of
      Leu, norleucine (nLeu). We conclude that D-forms of hydrophobic amino acids have
      lower affinity for similar or the same intracellular binding sites involved in
      the acid-extractable pool than in their L-forms. The significance of these
      findings to amino acid pools in cells, and to the predominance of L-forms of
      amino acids in the biosphere is considered

PMID- 9022294
TI  - Phosphorylation of a 25 kDa protein is induced by thermostable direct hemolysin
      of Vibrio parahaemolyticus.
AB  - Thermostable direct hemolysin (TDH) is a possible virulence factor produced by
      Vibrio parahaemolyticus. Although TDH has a variety of biological activities,
      including hemolytic activity, the biochemical mechanism of action remains
      uncertain. Here we analysed biochemical events, especially phosphorylation,
      caused by TDH in erythrocytes, and found that TDH caused significant
      phosphorylations of proteins on erythrocyte membrane. Phosphorylation of proteins
      was studies using [gamma-32P] ATP and SDS-PAGE. A number of protein kinase
      inhibitors were tested, to determine which types of kinases were involved in the
      phosphorylation events. TDH induced the phosphorylation of two proteins on
      membranes of human erythrocyte that are sensitive to TDH. The estimated molecular
      weight of these proteins was 25 and 22.5 kDa. Interestingly, the 22.5 kDa, but
      not the 25 kDa protein, was phosphorylated on the membrane of TDH-insensitive
      (resistant) horse erythrocytes. Moreover, a mutant TDH (R7), which retained
      binding ability but lost hemolytic activity, also phosphorylated only the 22.5
      kDa protein on human erythrocyte membranes. Among the protein kinase inhibitors
      used the protein kinase C inhibitors, (staurosporine and calphostin C) showed
      marked inhibition of phosphorylation of 25kDa protein. In addition to
      phosphorylation, these protein kinase C inhibitors suppressed hemolysis by TDH.
      These results indicate that the phosphorylation of the 25 kDa protein seems to be
      essential for the hemolysis by TDH after it binds to erythrocyte membranes.

PMID- 9022295
TI  - Primary culture of chicken hepatocytes in serum-free medium (pH 7.8) secreted
      albumin and transferrin for a long period in free gas exchange with atmosphere.
AB  - To study liver functions of chicken, we examined the primary culture of chicken
      hepatocytes, and found an easy method of long-term culture with free atmosphere
      exchange. Chicken hepatocytes were obtained by collagenase perfusion and cultured
      at 37 degrees C as a monolayer without substratum in serum-free L-15 medium (pH
      7.8) with free atmosphere exchange. The amounts of albumin and transferrin in
      medium were assayed by ELISA. The culture of chicken hepatocytes was maintained
      in the serum-free L15-medium )pH 7.) and 37 degrees C with free atmosphere
      exchange for 20 days. The amount of albumin secreted in the medium decreased to
      low levels early in culture; however, this was followed by marked increase from
      day 9 to day 17 of culture. The amount of transferrin was constant until day 6,
      then it too increased with further culture. We reported an easy method for the
      simple monolayer culture of chicken hepatocytes in serum-free L12 medium (pH 7.8)
      with free atmosphere exchange over an extended period. Expression of liver
      specific functions, viz. albumin and transferrin synthesis, was observed after 1
      week of culture.

PMID- 9022296
TI  - The effects of in vivo and in vitro non-enzymatic glycosylation and glycoxidation
      on physico-chemical properties of haemoglobin in control and diabetic patients.
AB  - The erythrocyte deformability, which is related to erythrocyte internal
      viscosity, was suggested to depend upon the physico-chemical properties of
      haemoglobin. In the present study we employed ESR spectroscopy on order to
      explore further the extent to which the in vivo or in vitro glycation and/or
      glycoxidation might affect haemoglobin structure on conformation. We revealed
      that under both in vivo and in vitro conditions the attachment of glucose induced
      a mobilization of thiol groups in the selected domains of haemoglobin molecules (
      the increased h+1/h0 parameter of maleimide spin label, MSL; 0.277 +/- 0.021 in
      diabetics vs 0.338 +/- 0.017 in controls, n = 12, P < 0.0001). The relative
      rotational correlation time (tau c) of two spin labels, TEMPONE and TEMPAMINE,
      respectively, in erythrocyte insides (5.22 +/- 0.42 in diabetics, n = 21 vs 4.79
      +/- 0.38, n = 16 in controls, P < 0.005) and in the solutions of in vitro
      glycated haemoglobin, were increased. Neither oxidation nor crosslinking of thiol
      groups was evidenced in glycated and/or oxidized haemoglobin. In addition,
      erythrocyte deformability was found to be reduced in type 2 diabetic patients
      (6.71 +/- 1.08, n = 28 vs 7.31 +/- 0.96, n = 21, P < 0.015). In conclusion, these
      observations suggest that: the attachment of glucose to haemoglobin might have
      decreased the mobility of the Lys-adjacent Cys residues, thus leading to the
      increased h+1/h0 parameter of MSL. Such structural changes in haemoglobin owing
      to non-enzymatic glycosylation may contribute to the increased viscosity of
      haemoglobin solutions (r = 0.497, P < 0.0035) and the enhanced internal viscosity
      of diabetic erythrocytes (r = 0.503, P < 0.003). We argue that such changes in
      haemoglobin, and consequently in red blood cells, might contribute to the
      handicapped oxygen release under tissue hypoxia in the diabetic state.

PMID- 9022297
TI  - Metabolism of adenosine and deoxyadenosine by human erythrocytes and CCRF-CEM
      leukemia cells.
AB  - Human lymphocytes lacking adenosine deaminase die and T-cell leukemias are killed
      by deoxycoformycin (dCf), an inhibitor of adenosine deaminase, due to impaired
      metabolism of dAdo. The initial metabolism of exogenous adenosine (Ado) and
      deoxyadenosine (dAdo) has been compared in human erythrocytes and CCRF-CEM
      leukemia cells and the data obtained have been simulated using kinetic constants
      obtained in vitro for the enzymes involved. Cells were mixed with 3H-labelled Ado
      and dAdo, samples were taken at 3 sec intervals and progress curves for the 3H
      labelled metabolites formed were determined by quantitative two-dimensional thin
      layer chromatography. Erythrocytes rapidly take up Ado and the predominant
      metabolite after 60 sec is hypoxanthine (Hyp), while for dAdo, deoxyinosine
      (dIno) predominates. By contrast, leukemia cells convert to Ado predominantly to
      AMP, while dAdo is converted first to Hyp and the to AMP. The presence of dCf had
      little effect upon Ado metabolism by induced accumulation of dAdo. Erythrocytes
      rapidly degrade Ado and dAdo to Hyp, although the phosphorolysis of dIno is
      relatively slow. Human CCRF-CEM leukemia cells convert most of the Ado or dAdo to
      AMP after 60 sec. For dAdo, the sequence of reactions would be dAdo-->dIno-->Hyp-
      >IMP-->sAMP-->AMP. dCf does not significantly affect the conversion of Ado-->AMP,
      but dCf blocks AMP accumulation from dAdo, consistent with the reaction sequence
      shown above. A computer model has been developed for the metabolism of Ado and
      dAdo, but some of the kinetic constants determined in vitro for this model do not
      pertain to intact cells.

PMID- 9022298
TI  - Influence of phospholipid composition on excretion of beta-lactamase from a
      stringent/relaxed Escherichia coli K 12 strain pair.
AB  - In comparison to stringent (relA+) controlled Escherichia coli cells, relaxed
      (relA) controlled E. coli cells excreted more recombinant beta-lactamase into the
      culture medium. The analysis of the composition of phospholipid fractions of the
      cells yielded increased levels of phosphatidylserine in relaxed controlled cells.
      We added various phospholipid vesicles to growing cells in order to influence the
      excretion rate via their incorporation in the membranes. The addition of vesicles
      to phosphatidic acid, phosphatidylglycerol and phosphatidylserine reduced the
      excretion of beta-lactamase whereas vesicles of phosphatidylethanolamine and
      phosphatidylcholine decreased or increased the excretion of beta-lactamase in
      dependence on the individual fatty acid residues of the added phospholipids. The
      lower the degree of saturation of the added phospholipids the more permeable was
      the cell envelope for beta-lactamase.

PMID- 9022299
TI  - Longitudinal monitoring of latent and active human cytomegalovirus infections in
      peripheral blood of heart transplant recipients by single-tube nested RT-PCR.
AB  - PCR is a sensitive diagnostic tool for the detection of human cytomegalovirus
      (HCMV) DNA in the peripheral blood of immunosuppressed transplant recipients.
      However, its specificity as a prognostic marker for clinical disease is
      unclassified, because infections considered to be latent may be detected by this
      method. In order to diagnose active viral infections, we used reverse
      transcription-PCR (RT-PCR) to identify HCMV mRNA in blood. We developed a single
      tube nested RT-PCR with preformed PCR mixtures embedded in a trehalose matrix.
      Blood samples of 48 heart transplant recipients were investigated for HCMV DNA. 8
      patients detected to be HCMV DNA positive after transplantation were investigated
      in longitudinal monitoring for at least 6 months. HCMV mRNA was found in 5
      patients who developed HCMV related symptoms during the period of RNA detection.
      There was no clear relation between the onset of DNA detection and the first
      demonstration of mRNA. In 2 patients HCMV DNA could be detected 74 and 81 days
      before the appearance of mRNA, suggesting long persistence until active infection
      is started. In 3 patients HCMV mRNA disappeared during or immediately after the
      end of ganciclovir therapy. In contrast, HCMV DNA was detectable continuously for
      prolonged periods after therapy, indicating that the persistence of HCMV DNA is
      not influenced by ganciclovir treatment. In summary, HCMV DNA detection seems to
      be a reliable early marker for the differentiation of persistent and active HCMV
      infections in immunosuppressed patients. Our data show that viral mRNA detection
      is probably a better predictor of the effectiveness of antiviral therapy than
      viral DNA detection.

PMID- 9022300
TI  - Molecular cloning and homology modeling of protocatechuate 3,4-dioxygenase from
      Pseudomonas marginata.
AB  - The genes that encode the alpha and beta subunits of protocatechuate 3,4
      dioxygenase (3,4-PCD [EC 1.13.11.3]) were cloned from a Pseudomonas marginata
      genomic library. These genes pcaG and pcaH, were found when screening the library
      for hydrolase genes. The two open reading frames of the PCD genes could be
      identified adjacent to an esterase gene by sequence homology. A 1.7-kb KpnI/ApaI
      fragment, carrying pcaG and pcaH, was subcloned and the genes were functionally
      expressed in Escherichia coli. The deduced amino acid sequence shows high
      homology to previously determined amino acid sequences of bacterial
      protocatechuate 3,4-dioxygenases. A homology model based on the available crystal
      structure of the protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa
      shows high similarity with the binding and catalytic sites.

PMID- 9022301
TI  - Transfer of attaching and effacing from a strain of enteropathogenic Escherichia
      coli to E. coli K-12.
AB  - The ability to cause attaching and effacing (AE) lesions in intestinal epithelial
      cells is an essential virulence trait of enteropathogenic E. coli (EPEC) that
      requires several chromosomal genes acting in concert with one another. In this
      study, we show that the ability to cause AE lesions can be transferred by
      conjugal mating from a high frequency recombinant (Hfr) derivative of a rabbit
      EPEC strain, E. coli RDEC-1, to a strain of E. coli K-12. Although the recipient
      acquired a considerable amount of donor DNA during the transfer process, it
      expressed the AE phenotype phenotype only weakly. The findings suggest the AE is
      a multigene phenomenon, the genes for which may not reside on a single region of
      the bacterial chromosome.

PMID- 9022302
TI  - Labeling Salmonella live vaccine strains with the lux operon from Vibrio fischeri
      improves their detection and discrimination from wild type.
AB  - Genetic labeling of Salmonella live vaccine strains, ZoosaloralR H and TAD
      Salmonella vacR T, with part of or the entire lux operon of the marine bacterium
      Vibrio fischeri allows for detection and discrimination of these vaccine strains
      in the course of routine bacteriological culture procedures, without disturbance
      of such procedures and without the requirement for extra materials and working
      steps. The label is either plasmid coded or chromosomally integrated by a Tn5
      transposon vector. One of the plasmid constructs contains a truncated lux operon
      raising the requirement for the exogenous addition of the aldehyde substrat of
      the luciferase to induce light production. All strains constructed produced light
      sufficiently bright to detect their colonies on the surface of a routinely used
      plate in the dark with the naked eye.

PMID- 9022303
TI  - Enumeration of bacterial and yeast colonists of apple fruits and identification
      of epiphytic yeasts on pear fruits in the Pacific Northwest United States.
AB  - A procedure for the isolation of diverse culturable microflora for the estimation
      of the population size of yeasts and bacteria on the surface of pome fruits is
      described. Maximum numbers of morphologically distinct colonies of both yeasts
      and bacteria were recovered from apple fruit surfaces when fruits were shaken for
      5 min in sterile phosphate buffer plus tween, sonicated for 5 min, and aliquots
      of the buffer plated onto diluted yeast malt agar and diluted nutrient broth
      agar, respectively. The yeast and bacterial populations on the surface of
      unsprayed Golden Delicious apple fruits were approximately 8.0 x 10(3) and 9.5 x
      10(4) colony forming units (cfu) per cm2, respectively. The densities of yeasts
      on the surface of pear fruits collected from Yakima, Wa, Cascade Locks, Medford,
      and Hood River, OR, were approximately 7.3 x 10(3), 6.4 x 10(3), 4.1 x 10(3), and
      9.9 x 10(2) cfu.cm-2, respectively. The highest number of morphologically
      different yeast isolates were recovered from pear fruits from Cascade Locks and
      Hood River, Oregon and Yakima, Washington. Aureobasidium pullulans was present on
      fruits in all pear orchards sampled whereas Cryptococcus albidus and Rhodotorula
      glutinis were isolated from 80% of the orchards. Other yeasts colonizing pear
      fruit surfaces in 20-60% of the orchards were Cryptococcus infirmo-miniatus,
      Cryptococcus laurentii, Debaryomyces hansenii, Rhodotorula aurantiaca, R.
      fujisanensis, R. minuta and Sporobolomyces roseus.

PMID- 9022304
TI  - Strains of the genus Serratia as beneficial rhizobacteria of oilseed rape with
      antifungal properties.
AB  - Isolates of Serratia have been isolated from the rhizosphere of oilseed rape. The
      percentage of Serratia in this microenvironment was determined as 12.4% of the
      total antifungal bacteria. Serratia liquefaciens, S. plymuthica and S. rubidaea
      were found. All of the isolates showed an antifungal activity against different
      phytopathogenic fungi in vitro but the efficiency of strains was different. The
      antifungal mechanisms of 18 selected strains were investigated. Direct antifungal
      effect may be based on antibiosis (production of prodigiosin and pyrrolnitrin)
      and production of lytic enzymes (chitinases and beta-1,3-glucanases). Potent
      siderophores were secreted by the strains to improve the availability of iron. No
      strain was able to produce cyanide. Most of the strains secrete the plant growth
      hormone indole-acetic-acid which can directly promote the growth of roots. The
      mechanisms were specific for each isolate.

PMID- 9022305
TI  - [Retinal and optic nerve transplantation].

PMID- 9022306
TI  - [Current topics in glaucoma].
AB  - Among the many factors involved in the development of glaucoma, the elevation of
      intraocular pressure (IOP) is the most important. The treatment of glaucoma aims
      to lower IOP in order to maintain visual function. New anti-glaucoma drugs,
      latanoprost and nipradilol, have been shown to effect a reduction in IOP equal to
      that achieved with the equivalent dosage of timolol, with no adverse systemic
      side effects. The mechanism of the reduction of IOP by these drugs mainly
      involves the increase of uveoscleral outflow. The success rate of filtering
      surgery for glaucoma has been increased by using antimetabolites such as
      mitomycin C (MMC) and 5-fluorouracil (5-FU). The use of MMC during surgery has
      resulted in a better outcome than with 5-FU. Normal tension glaucoma (NTG) cases
      are reported to constitute more than 60% of total glaucoma cases in Japan. NTG is
      different from primary open-angle glaucoma not only in IOP but also in the
      pattern of the visual field defect, cupping and peripapillary atrophy of the
      optic nerve head (ONH). The first choice of treatment for NTG is using drugs for
      reducing IOP and, if necessary, argon laser trabeculoplasty. In addition to these
      treatments a drug for increasing the blood circulation in the brain,
      brovinecamine fumarate, has shown beneficial effects in the treatment of NTG. NTG
      patients whose visual field can be shown by static perimetry to be deteriorating
      are indicated for filtering surgery. The results of filtering surgery for NTG
      have been confirmed that it is more effective than drugs for maintaining the
      visual field. We have developed an instrument using the laser speckle phenomenon
      for determining the microcirculation in the eye, as well as in the ONH,
      noninvasively, quantitatively, and repetitively. With the same instrument, the
      effects of anti-glaucomadrugs on ocular circulation, especially in the ONH, can
      also be determined. Timolol has no effect on the circulation in the ONH, but
      carteolol and betaxlol increase the circulation significantly. The Ca(+2)
      blocker, nilvadipine, increases the circulation in the ONH. These findings
      indicate that the drugs increasing the ONH circulation many be beneficial for the
      control of glaucoma.

PMID- 9022308
TI  - [Optic nerve regeneration by nerve transplantation].
AB  - The optic nerve fibers of adult mammals, once injured, can not regenerate
      spontaneously. However, from recent studies it has become clear that when their
      extracellular environment is replaced with that of the peripheral nervous system,
      namely surrounded with Schwann cells, they can regenerate their axons through the
      grafted nerve. Previous studies on the optic nerve regeneration by peripheral
      nerve transplantation have been done mostly in rats or hamsters. With an
      expectation of clinical application in future, we studied the optic nerve
      regeneration of adult cats because a great deal of knowledge on the optic nerve
      fibers and retinal ganglion cells had been accumulated. From recent series of
      studies we have obtained following results. 1. Retinal ganglion cells that
      regenerated axons constitute 2--4% of the total population, and among several
      types of ganglion cells, alpha cells have the greatest capacity for axonal
      regeneration. The ability of alpha cells for axonal regeneration is related to
      their relative resistance to axotomy. 2. Retinal ganglion cells with regenerated
      axons preserve their original dendritic fields, but their axons are thinner than
      normal, and mostly unmyelinated. 3. Single unit activities recorded from teased
      fibers of regenerated axons revealed that the units have mostly normal receptive
      field properties, enabling us to classify them into Y, X or W cells. 4. Amplitude
      reduction of pattern reversed electroretinogram (ERG) after the optic nerve
      section was slowed, to some extent, by the peripheral nerve transplantation. How
      we can reconnect these regenerated optic nerve fibers to the target neurons in
      the central visual system is a matter for future study.

PMID- 9022307
TI  - [Cellular and molecular biology of ischemic retina].
AB  - We introduce our studies on the retinal ischemia in light of both pre- and post
      Noell viewpoints. For several years now, we have employed in vivo intraretinal
      microelectrodes for this field of experiments. This series of studies on the cat
      eye revealed that the sensory retina as well as the retinal pigment epithelium is
      severely damaged after only a ten-minute stoppage of blood flow. This phenomenon
      in usually masked in the routine electroretinogram, a mass electrical response of
      the retina monitored from the ocular surface. Our studies, employing cultured
      amacrine cells from embryonic rat eyes, revealed that ischemic changes in neural
      cells are induced by an increase in extracellular glutamate. Among the glutamate
      analogs, N-methyl-D-aspartate (NMDA) is responsive to this change. An influx of
      calcium through NMDA receptor channels activates nitric oxide synthase (NOS),
      inducing intracellular nitric oxide (NO) in selected amacrine cells. Nitric oxide
      reacts with free radicals in the cell and induces peroxinitrite, which is toxic.
      This cascade triggered by ischemia is interrupted by extracellular zinc,
      magnesium, hemoglobin, nitroprusside, s-nitrosocysteine, and some NMDA
      antagonists. In terms of clinical application, there is a possibility that
      dihydroxyphenylalanine (DOPA), superoxide dismutase (SOD), and catalase (CAT), as
      well as vitamins B6 and B12, are important candidates for administration before
      an ischemic attack for prevention of damage to the retinal neurons. Gene
      expression of NOS, interleukin (IL)-1, IL-6, tumor necrosing factor (TNF), and
      transforming growth factor (TGF)-beta in the ischemic retina was investigated in
      order to discover reaction substances common to ischemic change and inflammation.

PMID- 9022309
TI  - [Axonal regeneration of retinal ganglion cells].
AB  - We have developed retinal culture system of adult mammals to investigate neural
      regeneration from adult retinal ganglion cells (RGC). In this culture system,
      neurites were regenerated from RGCs of adult retinal explants. Investigation of
      neurotrophic effects on the neural regeneration showed that some interleukins and
      neurotrophins enhanced neurite regeneration from adult rat RGCs. We also found
      that the adult human retina had the ability of neural regeneration and that
      neurotrophins enhanced this ability. A novel neurotrophic factor secreted by
      adult rat hepatocytes also enhanced neurite regeneration not only in adult mice
      but also in aged RGCs. This result indicated the novel hepatocyte secreted factor
      is an activator which enhances neural regeneration of the aged retina. We
      concluded that even adult aged RGCs had the ability of axonal regeneration after
      injury and that neurotrophic factors might enhanced these abilities. Therefore
      neurotrophic factors might have practicable applications in drug treatments for
      intractable disease of the neural retina and optic nerve. Future progress of
      neuroscience is expected to rescue the retina from various diseases, and to
      render possible the transplantation of the retina and optic nerve.

PMID- 9022310
TI  - [Retinal pigment epithelial cell transplantation: perspective].
AB  - Age-related macular degeneration is one of the most serious diseases in elderly
      people because of its disasterous visual outcome and its prevalence. Even if the
      submacular and choroidal neovascular membranes could be surgically excised,
      severe damage or evacuation of retinal pigment epithelium is inevitable in the
      operated area. Pigmentary dystrophy is also a devastating hereditary eye disease
      with severe visual disturbance. Up to now, there have been no effective
      treatments for either of them. We conducted basic experiments on retinal pigment
      epithelium (RPE) culture, transplantation of the cells to the subretinal space of
      animals, especially, the Royal College of Surgeon's (RCS) rat, a model of
      hereditary retinal degeneration, and observed their effects in preventing
      photoreceptor cell death. 1) We reviewed recent reports of RPE function in
      relation to cytokine production and autocrine/paracrine function of these
      ligands. Some cytokines with strong mitogenic effects as nerve trophic/growth
      factors were able to rescue photoreceptor cell death in dystrophic, ischemic, and
      light-damaged retinas in the rats. We transplanted allograft pigmented RPE from
      Long Evans rats or xenograft, human and bovine RPE into the subretinal space of
      RCS rats, and could observe the retardation of the photoreceptor cell death. 2)
      As a source of human transplantable RPE in clinical practice, we could use
      patients' own RPE cells as autografts or those from aborted human fetus eyes as
      allografts. At present, we cannot use RPE cells from different species as
      xenografts. We tried to obtain enough RPE cells for culture in vitro from
      patients with large or giant retinal tears, but were unsuccessful. Cells were
      easily obtained from fetus eyes, and could be cultured and transplanted as fresh,
      primary, or multiple passage cells. We also tried cryopreservation of these cells
      for up to 3 months. Enzymatic expression of tyrosinase, tyrosinase related
      protein I and II and some other enzymes was examined by proliferating chain
      reaction to detect possible transformation during the procedure. The cell
      characteristics were well preserved. In the future, if these RPE cells could be
      safely kept and available in deep-frozen condition, we could use them clinically
      at the appropriate time and in appropriate numbers for patients as an "RPE bank"
      just like an "eye bank" for corneal transplantation. 3) Immunological reaction is
      very important if we consider this technique for clinical application. Up to now,
      in experimental animals, no immunological reaction has been reported even for
      xenograft human RPE in rats, in funduscope and histological examination, because
      the intraocular space is an immunologically privileged site. But transplantation
      of human RPE cells with a collagen sheet into the anterior chamber in rabbits
      caused a definite reaction detected by suppression of the electroretinogram and
      macrophage infiltration into the subretinal space, not only in the operated eye
      but also in the contralateral non-operated eye. These results suggest that we
      must be cautious in clinical use of heterogeneous RPE transplantation. The
      expression of MHC class II cells was observed in the course of photoreceptor cell
      degeneration in the RCS rats but it was suppressed if they were rescued by the
      transplantation of human cultured RPE in these animals. 4) For clinical
      application of this technique, autografts are naturally much better than the xeno
      grafts or allografts. We tried to use iris pigment epithelium (IPE) for
      transplantation because it consists of pigmented cells of neural origin and
      enough could be obtained with ease by peripheral iridectomy. We also tried
      transfection of a vector (pCNX2) or vector-inserted cDNA of rat bFGF into the rat
      IPE and transplanted into the subretinal space of RCS rats. These transfected
      cells expressed strong mRNA of bFGF. The photoreceptors were well preserved and
      immunological reaction could not be detected by funduscopical or histological
      examinat

PMID- 9022311
TI  - [49th annual meeting of the Japanese Association for Thoracic Surgery. October 15
      17, 1996. Kyoto, Japan. Abstracts].

PMID- 9022312
TI  - [Long-term effect of a beta-adrenergic agonist on Na+/K(+)-ATPase activity in rat
      lung explants].
AB  - To test the long-term effect of a beta-adrenergic agonist on Na+/K(+)-ATPase
      activity in rat lung explants, we measured the activity in lung explants kept
      continuously in the presence or absence of 0.1 mM terbutaline for 5 days. Once it
      was clear that this agent increased Na+/K(+)-ATPase activity, we then performed a
      similar measurement in cultured alveolar type II cells from rats. Continuous
      exposure to 0.1 mM terbutaline enhanced the enzyme activity in those cells, and
      this enhancement was completely blocked by 0.01 mM of the beta-antagonist
      propranolol. Western blotting showed that this increase in Na+/ K(+)-ATPase
      activity in the cells could involve modulation of protein expression. We conclude
      that beta-adrenergic agonists can increase Na+/K(+)-ATPase activity in alveolar
      type II cell in lung explants by modulating expression of the enzyme in a long
      period of time.

PMID- 9022313
TI  - [Infiltration of inflammatory cells and expression of adhesion molecules in
      bronchial mucosa of patients with asthma].
AB  - To study the infiltration of inflammatory cells and the expression of adhesion
      molecules, I examined bronchial tissue from atopic patients with asthma. T
      lymphocytes, macrophages, neutrophils, eosinophils, and mast cells in samples of
      bronchial mucosa were stained with monoclonal antibodies. The expression of
      adhesion molecules (ICAM-1, VCAM-1, ELAM-1, and PADGEM) in epithelium,
      endothelium, or both, were observed. Samples were obtained by biopsy from
      patients with asthma and from healthy control subjects. The numbers of mucosal T
      lymphocytes, eosinophils, and mast cells were significantly higher in tissue from
      the patients than in tissue from the control subjects. Immunostaining for ICAM-1
      was observed in both the epithelium and endothelium, but staining for VCAM-1 ELAM
      1, and PADGEM was seen only in the endothelium. Expression of adhesion molecules
      except ELAM-1 was found to differ significantly between patients and control
      subjects. Expression of VCAM-1 in endothelium correlated significantly with the
      number of eosinophils, and expression of ICAM-1 in epithelium correlated
      significantly with the number of mast cells. These results suggest that
      expression of adhesion molecules in bronchial mucosa play an important role in
      the migration of inflammatory cells in patients with asthma.

PMID- 9022314
TI  - [Surfactant protein A in bronchoalveolar lavage fluid from patients with
      idiopathic interstitial pneumonia].
AB  - We measured the levels of surfactant protein A (SP-A) in bronchoalveolar lavage
      fluid from patients with idiopathic interstitial pneumonia and from healthy
      volunteers. The SP-A levels in the patients who were smokers (1.4 +/- 0.2
      micrograms/ml) were significantly (p < 0.05) lower than those in the patients who
      were nonsmokers (3.0 +/- 0.5 micrograms/ml). However, SP-A levels did not differ
      significantly between patients and volunteers who were smokers, or between
      patients and volunteers who were nonsmokers. The ratios of SP-A to phospholipid
      in patients who were smokers and in those who were non-smokers did not differ
      significantly from those in volunteers who were smokers and volunteers who were
      non smokers. The total number of alveolar macrophages in bronchoalveolar lavage
      fluid did not significantly correlate with the level of SP-A, although the
      percentage of alveolar macrophages correlated negatively (p < 0.05) with the
      level of SP-A. The low level of SP-A in patients with idiopathic interstitial
      pneumonia who are smokers may weaken the host defense functions in peripheral
      airways and may contribute to the poor outcomes in these patients.

PMID- 9022315
TI  - [Six patients with pneumonitis related to blended Chinese traditional medicines].
AB  - We encountered six patients with pneumonitis related to blended chinese
      traditional medicine (Kampo). The duration of treatment with kampo ranged from 14
      to 110 days (mean: 38 days). The most common complaints were dyspnea, fever, and
      dry coughing. Fine crackles were heard at the bases of both lungs. Abnormal
      laboratory findings included high values of C-reactive protein and glutamic
      oxaloacetic transaminase in all patients, lactate dehydrogenase in 5 patients,
      and eosinophil count in 1 patient. Chest X-ray films and CT films revealed
      diffuse reticulo-nodular interstitial shadows with consolidation in both lung
      fields in 3 patients and pleural effusion in 1 patient. Bronchoalveolar lavage
      was done in 4 patients; examination of the lavage fluid showed lymphocyte
      alveolitis, either pure or associated with neutrophilia and eosinophilia in 3
      patients. Inverted CD4/CD8 lymphocyte ratios were found in 3 patients.
      Transbronchial lung biopsy was done in 4 patients and specimens from 3 of those 4
      showed organizing pneumonitis with thickening of alveolar septa. Lymphocyte
      stimulation tests were positive in 4 patients. Discontinuation of the drug (2
      patients) or administration of corticosteroids (4 patients) was followed by rapid
      improvement. Patients being treated with kampo preparations should be observed
      for signs and symptoms of drug-induced pneumonitis.

PMID- 9022316
TI  - [Psychological and physiological changes accompanying pulmonary rehabilitation in
      patients with chronic pulmonary emphysema].
AB  - In 14 patients with chronic pulmonary emphysema, the relations between changes in
      psychological status associated with pulmonary rehabilitation and exercise
      tolerance were studied with the Cornell Medical Index and the Yatabe-Guiford
      Personality Inventory. Although the scores on the latter did not change, the
      cardio-respiratory score on the Cornell Medical Index improved significantly (p <
      0.05). The only index of exercise tolerance that improved significantly was the
      distance walked in 10 minutes (p < 0.05). The changes in the scores of "Lack of
      Objectivity" and "Rhathymia" correlated negatively with the change in the
      distance walked in 10 minutes (R = -0.80, p < 0.01; R = -0.81, p < 0.01). The
      change in psychological status that accompanied pulmonary rehabilitation has been
      related to the improvement in the distance walked in 10 minutes.

PMID- 9022317
TI  - [Clinico-pathological analysis of airway abnormalities in patients with chronic
      eosinophilic pneumonia].
AB  - Chronic eosinophilic pneumonia is characterized by infiltration of eosinophils
      into alveolar spaces. Patients with this condition may also have asthmatic
      episodes, chronic coughing, and bronchorrhea, even after the infiltrative opacity
      on the chest roentgenogram resolves. We used computed tomography, pulmonary
      function tests, and biopsies to evaluate the airways of 11 patients with chronic
      eosinophilic pneumonia. The tomograms showed bronchial wall thickening in all
      patients at the time of the onset of symptoms and ten months later. Centrilobular
      peribronchovascular interstitial thickening was detected in four patients, 10
      months after the onset. Pulmonary function tests showed that small airway
      dysfunction remained 13 months after the onset. Pathological analysis revealed
      airway abnormalities that included basement membrane thickening and cellular
      infiltration 2 years after the onset. These results show that airway changes had
      not resolved even after roentgenographic opacities had disappeared. More
      attention should be given to treatment of airway disease associated with chronic
      eosinophilic pneumonia, and to whether these changes in the airway are similar to
      those seen in bronchiolitis obliterans organizing pneumonia.

PMID- 9022318
TI  - [Defensin in plasma and in bronchoalveolar lavage fluid from patients with acute
      respiratory distress syndrome].
AB  - We measured the levels of defensins, antimicrobial peptides, and cytotoxic
      peptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar
      lavage fluid (BALF) from patients with the acute respiratory distress syndrome
      (ARDS). High levels of plasma defensins were observed in samples from patients
      with ARDS. Samples of BALF from patients with ARDS also had more neutrophils and
      higher concentrations of defensins than did samples from healthy volunteers and
      from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis. In
      addition, the concentration of interleukin (IL)-8 in BALF was higher in patients
      with ARDS than in other subjects. A significant correlation was found between the
      concentration of defensins and that of IL-8 in BALF from patients with ARDS.
      These findings suggest that the lung injury in ARDS is caused by defensins
      released by neutrophils that accumulate in the lungs.

PMID- 9022319
TI  - [Clinicopathological study of pulmonary hamartoma with special reference to 6
      patients who also had another tumor].
AB  - We studied 22 patients in whom intrapulmonary hamartoma was diagnosed between
      1975 and 1994. Twelve were men and 10 were women, and their ages ranged from 20
      to 72 years (averaged: 52.5). The sizes of the hamartomas ranged from 5 mm to 3
      cm. Five patients also had other types of cancer (ling 3, colon 1, thyroid 1) and
      one had a mediastinal tumor (1). In those 6 patients, the hamartomas had to be
      distinguished from intrapulmonary metastasis. In 2 of those 6, thoracoscopic
      surgery was useful for obtaining sufficient materials for diagnosis. In one
      patient immunohistochemical analysis with anti-PCNA (proliferative cell nuclear
      antigen) antibody was useful in distinguishing leiomyomatous hamartoma from
      benign metastatic leiomyoma.

PMID- 9022320
TI  - [Matured mediastinal teratoma with high levels of tumor markers in cystic fluid].
AB  - A 42-year-old woman was admitted to Gifu Municipal Hospital because of an
      abnormal mediastinal shadow on a chest X-ray film. The serum CA125 level was
      slightly high 38 U/L, normal: < 35 U/L. Preoperative examination of fluid from a
      cyst revealed a high level of carcinoembryonic antigen (550 ng/ ml). The tumor
      resected was 11 x 9 x 5 cm. Microscopic examination revealed a matured teratoma
      containing pancreatic cells, collagenous tissues, squamous epithelia, and hair
      follicle-like tissues. Biochemical analysis of the cystic fluid revealed high
      levels of eight tumor markers: carcinoembryonic antigen, CA125, CA19-9, SLX,
      Ferritin, NSE TPA, and elastase 1. Samples stained positively for the tumor
      markers carcinoembryonic antigen CA125, CA19-9, and NSE by ABC
      immunohistochemical staining. The serum carcinoembryonic antigen levels had
      decreased to the normal level within two weeks after the surgery. The high levels
      of tumor markers and materials in the cystic fluid may have been related to the
      biological characteristics of the various cell components in this matured
      teratoma.

PMID- 9022321
TI  - [Squamous cell carcinoma of unknown origin affecting mediastinal lymph nodes].
AB  - A 65-year-old woman was admitted to the hospital because of an abnormal shadow on
      a chest X-ray film. Chest CT scans showed enlargement of the right mediastinal
      lymph nodes. However, no primary lesion was detected despite thorough
      examination. Mediastinoscopic biopsy revealed that the tumor was a lymph-node
      metastatic lesion of a squamous cell carcinoma of unknown origin. A thoracotomy
      was done and the mass was completely resected. Radiotherapy was given after the
      operation. We have followed the patient for 1 year since the operation, but no
      primary lesion has yet been detected. Metastasis of cancer of unknown origin to
      hilar or mediastinal lymph nodes is extremely rare, and only 6 cases have been
      reported previously in the Japanese medical literature.

PMID- 9022322
TI  - [Sjogren's syndrome complicated by thymoma].
AB  - A 43-year-old woman with a history of Sjogren's syndrome was admitted to our
      hospital because of dyspnea due to anemia. Her chest X ray film on admission
      revealed an anterior mediastinal tumor. We diagnosed this tumor as a thymoma
      based on a chest CT scan and magnetic resonance imaging. Because the latter
      indicated that the thymoma may have involved the mediastinal great vessels,
      preoperative chemotherapy with cisplatin, doxorubicin hydrochloride, vincristine
      sulfate and cyclophosphamide. Thereafter the tumor was successfully resected
      along with part of the right pleura. Thymoma as a complication of Sjogren's
      syndrome is rare. Here we also discuss the treatment of thymoma and the
      combination of these two diseases.

PMID- 9022323
TI  - [Sarcoidosis in an 82-year-old woman who presented with ocular symptoms].
AB  - An 82-year-old woman with blurred vision consulted an ophthalmologist. She was
      admitted to the hospital (internal medicine) for further examination because of
      uveitis and cataracts. A chest X-ray film and a CT scan showed interstitial
      infiltration in the right middle lung field, and a Ga-scintigram showed abnormal
      accumulation in the same area. The mediastinal lymph nodes were not swollen, and
      the left lung appeared to be normal. We diagnosed her illness as sarcoidosis
      because the CD4/CD8 of bronchoalveolar lavage fluid from the right B4 was greater
      than 5.0 and because examination of a specimen obtained by transbronchial lung
      biopsy from the right B4 showed many non caseous epithelioid granulomas. In
      contrast bronchoalveolar lavage fluid from the left B4 had a CD4/CD8 of less than
      2.0 and examination of a biopsy specimen from the left B4 showed normal lung
      tissue. The lesion in this patient was only in the right lung, and was classified
      as Stage 3. However, because the lung fibrosis and the reduction in pulmonary
      function were minimal, the disease in this case did not fit the conventional
      classification into stages.

PMID- 9022324
TI  - [Pulmonary actinomycosis--diagnosis and therapy based on past reports of
      actinomycosis].
AB  - A 57-year-old man who complained of bloody sputum was admitted to the hospital
      because of a spherical mass on a chest X-ray film. Despite a detailed
      examination, no definitive diagnosis was obtained, and a left lower lobectomy was
      done. Histopathologic examination of tissue from the resected lobe revealed
      sulfur granules and branching filamentous bacteria, and therefore pulmonary
      actinomycosis was diagnosed. Examination of reports published in Japan in the
      last five years suggested a slight increase in the frequency of diagnosis before
      treatment of actinomycosis and a slight decrease in the frequency of surgical
      treatment. However, these changes are not surprising because the frequency of
      surgical treatment is 58%. These findings suggest that pulmonary actinomycosis
      should be included in the differential diagnosis of a mass on a chest X-ray film.

PMID- 9022325
TI  - [Eosinophilic pneumonia presenting as a mass shadow].
AB  - A 35-year-old man underwent routine chest roentgenography and a mass shadow was
      seen in the left lung field. Examination of a transbronchial lung biopsy specimen
      revealed that many eosinophils had infiltrated under the bronchial mucosa and
      into the alveolar septum. The total serum IgE concentration was high, and skin
      tests with Aspergillus antigen and serum precipitating antibodies against
      Aspergillus were positive. The mass lesion disappeared without any therapy, and a
      cystic lesion remained. Mediators released from eosinophils were thought to have
      damaged the lung tissue. We should have administrated corticosteroids as soon as
      possible.

PMID- 9022326
TI  - [Diffuse malignant mesothelioma associated with asbestos pleurisy].
AB  - Asbestos pleurisy is relatively uncommon among patients who present with pleural
      fluid. Association of diffuse malignant mesothelioma with asbestos pleurisy has
      not been reported in Japan, although 10 cases have been reported in the world
      literature. We encountered a 51-year-old man in whom diffuse malignant
      mesothelioma developed during a 5-year course of asbestos pleurisy. Mesothelial
      cells in patients with asbestos pleurisy are likely to be exposed to asbestos for
      a long time, which may increase the risk that mesothelioma will develop.

PMID- 9022327
TI  - [Repeated pneumonia in the middle lobe caused by congenital bronchoesophageal
      fistula].
AB  - A 52-year-old woman was admitted to our hospital because of repeated episodes of
      pneumonia in the middle lobe. She had also experienced coughing during meals. The
      history and chest CT findings suggested the presence of a bronchoesophageal
      fistula. An upper GI series revealed a fistula between an esophageal diverticulum
      and the superior segment bronchus of the right lower lobe. Fiberoptic
      bronchoscopy done immediately after the upper GI series revealed barium sulfate
      leaking from the superior segment bronchus of the right lower lobe into the
      middle lobe bronchus. These findings indicated that the repeated pneumonia in the
      middle lobe was caused by a congenital bronchoesophageal fistula. Examination of
      the resected fistula showed that it was a Braimbridge type I bronchoesophageal
      fistula. Although of at least 49 cases of congenital bronchoesophageal fistulas
      with esophageal diverticula have been reported in the Japanese medical
      literature, we know of no previous case in which such a fistula was associated
      with middle-lobe pneumonia.

PMID- 9022328
TI  - [Summer-type hypersensitivity pneumonitis in a family].
AB  - We encountered a family in which three of the five members (The parents and a
      daughter) had summer-type hypersensitivity pneumonitis that occurred in late
      summer. All three patients had a productive cough and shortness of breath. Chest
      roentgenograms of the mother and daughter (but not the father) showed diffuse
      small nodular shadows in both lung fields. Examination of bronchoalveolar lavage
      fluid from all three patients showed very high total cell counts, high
      percentages of T lymphocytes, and low ratios of CD4(+)-to-CD8+ cells. Microscopic
      examination of transbronchial biopsy specimens obtained from the daughter
      revealed infiltration of mononuclear cells with characteristic Masson bodies in
      alveolar septa, and granulomas in the interstitium. Both mother and daughter were
      positive for serum anti-Trichosporon cutaneum (serotype II) antibody, but the
      father, who was a current smoker was not. Thus, both mother and daughter were
      given the diagnosis of summer-type hypersensitivity pneumonitis, and in the
      father that diagnosis was strongly suspected.

PMID- 9022329
TI  - [Selenium deficiency associated with cardiac dysfunction in three patients with
      chronic respiratory failure].
AB  - We encountered three patients with chronic respiratory failure who had heart
      failure of cardiac arrhythmias and low levels of serum selenium. All three had
      tracheostomies and had received long-term parenteral nutrition that had not
      included selenium. All three also had refractory cardiac dysfunction, which was
      manifested in edema, heart failure, and various tachycardias. We suspected that
      selenium deficiency had caused their cardiac dysfunction. Serum selenium
      concentrations were found to be much lower than normal in all three, so 100
      micrograms/day of selenium was administered in addition to their tube feedings.
      Cardiac function improved after replacement of selenium. These cases show the
      need for preventing selenium deficiency in patients with chronic respiratory
      failure during long-term administration of parenteral nutrition.

PMID- 9022330
TI  - [Tropical eosinophilia in a man from Sri Lanka].
AB  - A 21-year-old man from Sri Lanka came to Japan in August 1992 and worked as a
      painter. He had often complained of dyspnea on exertion before coming to Japan.
      He was admitted to Ogaki Municipal Hospital in June 1993 for further examination
      of persistent coughing, dyspnea, and fever. A chest X-ray film showed bilateral
      diffuse reticulonodular shadows. Blood examinations revealed marked eosinophilia
      (9440/mm3) with elevation of the serum IgE level (4982 IU/ml). IgG enzyme-linked
      immunosorbent assay showed a high titer against Dirofilaria immitis. Microfilaria
      were not detected in blood sampled at night. He was given a diagnosis of tropical
      eosinophilia. We could not give diethyl-carbamazine. Filariasis is seldom
      encountered in Japan, but we emphasize that parasitic disease such as tropical
      eosinophilia must be considered in the differential diagnosis if the patient is
      from a tropical area where filariasis is common.

PMID- 9022331
TI  - [A case of enlarging rounded atelectasis difficult to distinguish from a
      pulmonary neoplasm].
AB  - A 55-year-old man with occupational exposure to asbestos presented with a chest
      roentgenographic abnormality that was found during a physical check-up. Computed
      tomography disclosed pleural thickening and a pulmonary mass in the left lower
      lobe. A fine-needle biopsy was done, but the presence of a malignant lesion was
      not confirmed. The patient was asymptomatic. He was observed closely, and 10
      months later computed tomography showed that the mass had enlarged. A fine-needle
      biopsy was done again, but no evidence of malignancy was found. We suspected that
      it was rounded atelectasis, but could not rule out a neoplasm. An exploratory
      thoracotomy was done, and the histopathological findings showed that the mass was
      lung tissue with alveolar wall fibrosis that had resulted in thickening of the
      wall. The mass was diagnosed as rounded atelectasis. Rounded atelectasis requires
      no special treatment, but if the mass increases in size as in the case of this
      patient, an exploratory thoracotomy is required.

PMID- 9022332
TI  - [Pneumocystis carinii pneumonia associated with high levels of serum KL-6].
AB  - In May 1995, a 52-year-old man complaining of fever and dyspnea was admitted to a
      hospital. Based on clinical and radiographic findings, hypersensitivity
      pneumonitis was suspected. Steroid pulse therapy was unsuccessful, and he was
      then transferred to our hospital. A chest X-ray film showed bilateral ground
      glass shadows and a high-resolution CT scan showed cystic air spaces. The number
      of CD4-positive lymphocytes in peripheral blood was very low. A test for anti
      human immunodeficiency virus antibody was positive and Pneumocystic carinii was
      found in bronchoalveolar lavage fluid. The acquired immunodeficiency syndrome and
      Pneumocystis carinii pneumonia were diagnosed. In this patient, the level of
      serum KL-6, a new marker of interstitial pneumonitis, was very high, and KL-6 was
      expressed on type II pneumocytes. The level of serum KL-6 may be useful as a
      marker of the activity of Pneumocystis carinii pneumonia.

PMID- 9022333
TI  - [Pulmonary cavernous hemangioma--identification of its endothelial cell origin by
      immunohistological staining].
AB  - A 45-year-old woman was referred to our hospital because of a tumorous shadow in
      the S10 segment of the left lung. A chest computed tomography (CT) scan showed a
      nodular lesion with a slightly irregular margin and no contrast enhancement. CT
      guided aspiration biopsy was tried but did not result in a histological
      diagnosis. The tumor was excised during video-assisted thoracoscopic surgery.
      Histological examination of the specimen revealed cavernous hemangioma. Most
      cells lining the lumen of the cavernous structure stained positively for von
      Willebrand factor antibody and negatively for anti-epithelial membrane antigen
      antibody, which suggests that the tumor was associated with endothelium. To the
      best of our knowledge, this is the first report of a case in which the diagnosis
      of pulmonary cavernous hemangioma was confirmed with an immunohistological study.

PMID- 9022335
TI  - [Immune system and diseases that vary with circumstance and physical condition].
AB  - Empirically we all know that our immune system varies depending on environmental
      factors and physical conditions. However, such recognition has remained at an
      empirical level for a long time without the accumulation of scientific data. The
      major reason is that the substance and its receptor that connect physical
      conditions with the immune system have previously been obscure. Adrenergic and
      cholinergic receptors on leukocytes may be important in understanding that
      relationship. Furthermore, we have to consider the mutually antagonistic
      functions of granulocytes and lymphocytes in the body. All stimuli from
      environmental factors change our physical conditions and subsequent changes in
      the autonomic nervous system influence our immune system through adrenergic
      receptors on granulocytes and cholinergic receptors on lymphocytes.
      Overactivation of granulocytes induces purulent diseases or tissue destruction,
      whereas overactivation of lymphocytes induces allergic diseases.

PMID- 9022336
TI  - [Environmental allergens and allergic diseases].
AB  - Prevalence of allergic diseases in Japan has been increasing these 30 years.
      About 3%/5% of adult/ child general population are suffering from bronchial
      asthma these days. Housedust-mite, pollen, fungi and food have been identified as
      causative allergen. But recent change of life style in Japan is thought as the
      most important cause of increase of allergic diseases, such as change from life
      in wooden houses to concrete buildings. A full-day air-conditioning is
      comfortable not only for residents but also for microorganisms such as mite and
      fungi. Therefore, chance to expose to these allergens has been increasing. It is
      well-known that mite allergen is the most important causative allergen of
      bronchial asthma. Allergen analysis made us possible to measure the amount of
      allergen contents in our environment. It is known that 2 micrograms of Der 1
      allergen of mite per 1 g of dust is enough to sensitize the host and 10
      micrograms per 1 g dust can induce asthma attack. As mite allergens are rich in a
      sleeping mattress, asthma patients with mite allergy sometimes get asthma attack
      during sleeping at night. Pet dander such as cat and hamster are also popular
      causative allergens of asthma. About 30% of asthma patients show positive
      immediate skin response to these allergens. Releasing the pet from patients' home
      sometimes brought immediate relief from their symptoms.

PMID- 9022337
TI  - [Autoimmune diseases and stress proteins].
AB  - The heat shock protein(hsp), one of the most conserved and ubiquitous proteins in
      a wide range of species from bacteria to mammals, is strongly immunogenic. High
      conservation and potent immunogenicity, taken along with the fact that hsp is the
      target molecule of some gamma/delta T cells place it at the interface between
      immunity and tolerance. The role of hsp on autoimmune and inflammatory disorders
      has been vigorously investigated. There are accumulated lines of evidence
      suggestive of the possible involvement of hsp in clinical disorders but they
      still remain circumstantial. Two questions must be addressed before the exact
      role of hsp in these settings is established: 1) Why a conserved protein such as
      hsp is so immunogenic? 2) Why a ubiquitous protein can be a target of an organ
      specific autoimmunity? Our data indicated that antibodies against highly
      conserved hsp60 in the sera from patients with autoimmune diseases, highlighted
      by rheumatoid arthritis, were directed mainly against epitopes specific for
      bacteria such as E. coli. The role of intestinal flora on the pathogenesis of
      rheumatoid arthritis has long been pursued and our data might support these
      lines.

PMID- 9022338
TI  - [Stress and psychosomatic disease].
AB  - Psychosomatic disease has become almost synonymous with stress-related diseases.
      It is defined as a somatic disorder with influences from various types of stress.
      The physical reactions to stress are generally divided into three principal
      areas:those affecting the autonomic nervous system, the endocrine system or the
      immune system. However, recent studies show that these three areas actually
      affect one another and this, in turn, affects the body's homeostasis. In the
      stress-filled environment we live in, on-going research on psychosomatic disease
      and stress will continue to play a vital role in the diagnosis and treatment of
      disease.

PMID- 9022339
TI  - [Relations between stress in daily life and hypertensive cardiovascular
      accidents].
AB  - Hypertensive patients with cardiovascular disorders can encounter dangerous
      stress even during ordinary daily activities. Numerous cardiovascular
      accidents(ischemic heart attacks and strokes) occur during the morning hours,
      which are, therefore, from this perspective, the most dangerous part of the 24
      hour day. During the morning, both blood pressure and heart rate rise suddenly.
      Total peripheral resistance(TPR) also increases, whereas baroreceptor
      sensitivity(BRS) decreases in patients with essential hypertension. The following
      haemodynamics factors may contribute to these phenomena. During sleep, no food or
      drink is ingested; consequently, plasma volume decreases(hematocrit therefore
      increases), and the autonomic nervous system becomes unbalanced(the LF/HF ratio
      in heart rate variability increases); and BI[= Pd x RR/ (Pd0 x RR0)-1] decreases
      (Pd = diastolic blood pressure, RR = pulse interval, Pd0 = base Pd during
      sleeping hours, RR0 = base RR during sleeping hours) in the morning. These
      haemodynamics changes during the morning hours may diminish coronary blood flow.

PMID- 9022341
TI  - [Development of novel clinical tests and their contribution to laboratory
      diagnosis--ligase chain reaction].
AB  - There are several methods that have been developed for the detection of a small
      amount of nucleic acids. Ligase chain reaction(LCR) is a highly sensitive assay
      for the detection of a specific DNA sequence. LCR utilizes four
      oligodeoxynucleotides(probes) complementary to each of target DNA strands and
      repeats a thermalcycling amplification step. Two pairs of oligodeoxynucleotides
      renature adjacent to one another on each of the separated target DNA strands,
      resulting in nick formation. A thermostable DNA ligase joins the nick covalently.
      Each ligated product can serve as a template sequence in subsequent rounds of
      thermalcycling (denaturation, annealing/ligation). In this manner LCR accumulates
      the ligated products exponentially by repeating thermalcycling. One of the
      distinctive features of LCR is to be able to detect a known point-mutation
      easily. Gap-LCR, a modified LCR, has been developed to improve the sensitivity
      and the specificity of the standard LCR by setting up gaps (3 < or = nucleotides)
      at the ligatable 3' and 5' termini of the probes. The gap-LCR probes form a short
      gap after annealing of the probes to the target DNA. The gap is filled in by a
      thermostable DNA polymerase and the resultant nick is sealed by a thermostable
      DNA ligase to generate the ligated probes. Gap-LCR repeats this step on
      thermalcycling and accumulates the LCR products in an exponential fashion.

PMID- 9022342
TI  - [Determination of malondialdehyde-modified LDL(MDA-LDL) and its potential
      usefulness].
AB  - Numerous studies have indicated that oxidative modification of low-density
      lipoprotein(LDL) plays a critical role in the pathogenesis of atherosclerosis.
      Malondialdehyde-modified LDL(MDA-LDL) is one of the candidates which is the
      oxidative product of LDL. However, the existence of MDA-LDL in the circulation
      has been in dispute. Therefore, for the assessment of oxidized-LDL in human
      serum, we developed a sensitive enzyme-linked-immunosorbent assay(ELISA) for the
      detection of MDA-LDL. In our method, monoclonal antibody against MDA-LDL, ML25
      was used. ML25 recognized MDA-LDL as well as MDA-modified proteins by a solid
      phase competitive enzyme immunoassay. Therefore, to establish an ELISA method
      which is specific for detection of MDA-LDL, ML25 was combined with apoB-specific
      antibody (AB16) as the second antibody. Using this method, MDA-LDL was detectable
      in the sera of 314 healthy individuals. The concentration of MDA-LDL preferably
      ranged from 20 to 80 units/l when the absorbance with artificially prepared MDA
      LDL at the concentration of 1 mg/l was defined as 1 unit/l. Furthermore, assays
      for lipoprotein subfractions separated by density-gradient ultracentrifugation
      revealed that MDA-LDL was mainly distributed in the LDL fraction as expected, and
      MDA-LDL/apoB ratio showed a peak at small, dense LDL fractions. This finding
      seems to be quite interesting since an elevated level of small, dense LDL has
      been reported to be associated with an increased risk of atherosclerosis. We
      concluded that our method is useful for specific detection of MDA-LDL in human
      serum and might be an elevation method for atherogenicity.

PMID- 9022343
TI  - [Complete cholesteryl ester transfer protein deficiency increases oxidized-LDL in
      plasma].
AB  - Malondialdehyde-modified LDL(MDA-LDL) is one of the major oxidative LDL. MDA-LDL
      was determined by enzyme immunoassay in patients with complete and partial
      cholesteryl ester transfer protein(CETP) deficiency. Significantly increased
      serum MDA-LDL levels and MDA-LDL/apoB ratios in the LDL fraction were observed in
      patients with complete CETP deficiency but not for those with partial CETP
      deficiency. The present results may indicate that patients with complete CETP
      deficiency have a higher risk for atherosclerosis than those with partial CETP
      deficiency and normal.

PMID- 9022344
TI  - [Clinical application of gene technology for diagnosis and treatment of
      leukemia].
AB  - Recently, clinical application of gene technology in oncology and hematology has
      been markedly advanced. Pathogenesis of leukemic transformation has been thought
      that it was resulted from cumulation of activation or mutation in oncogenes or
      onco-suppressor genes. As a matter of fact, many specific chromosomal
      abnormalities in leukemias have been thought to be due to production of chimeric
      fusion gene by translocation and activation in some kinds of oncogenes under
      specific regulatory genes after translocation. In addition to those, inactivation
      of onco-suppressor genes, such as RB gene or p53 gene, may be also related to
      leukemogenesis in some leukemias. Laboratory examinations using molecular
      technology are being necessary for clinical diagnosis and treatment in many
      hematological disorders. The examinations detecting rearrangement of major BCR or
      minor BCR in Ph1 positive leukemias, TCR in T cell malignancy, immunoglobulin in
      B cell malignancy, PML-RAR alpha fusion gene in APL have become routine for
      diagnosis of some leukemias. Moreover, these examinations are useful for
      judgement of treatment effects and evaluation of minimal residual diseases. In
      this paper, we also discuss the usefulness and importance of these technology
      especially in stem cell transplantation and cytokine therapy, and the future
      possibility in this technology for gene therapy.

PMID- 9022345
TI  - [Hematological evaluation of megakaryocytic vacuolar degeneration in patients
      with idiopathic thrombocytopenic purpura].
AB  - Variable degrees of vacuolar degeneration of the cytoplasm of megakaryocytes(MEG)
      have been recognized in patients with idiopathic thrombocytopenic purpura(ITP).
      It has been questioned whether this degeneration is specific to the disease, as
      it is not seen in all patients, and few reports have examined its physiological
      relationship to the disease process. This study examined the vacuolation and its
      relationship to platelet count(PLTc) by image analysis, measuring the vacuolar
      area and the MEG area. However, it was inappropriate to evaluate the vacuolar
      area alone, since variations in the MEG area among patients influenced the
      vacuolar area. When the proportion of the vacuolar area relative to total MEG was
      defined as %VAC, the value for ITP patients was higher than in control cases (p <
      0.05). However, there was no correlation between %VAC and PLTc. It was thought
      that this reflected the previous reports doubting the disease specificity of this
      feature. When all the ITP patients were generalized, the age at onset was wide,
      and both chronic type and repetitive type cases were included. However, in 4 ITP
      cases in which it was possible to follow the treatment progress, the %VAC was
      well correlated with the change in PLTc. It was concluded that MEG cytoplasmic
      vacuolation in ITP is morphologically meaningful if it can be followed over the
      course of treatment.

PMID- 9022346
TI  - [Analysis of mechanism of increased platelet counts during preoperative
      autologous blood donation].
AB  - Autologous blood transfusion is advantageous in that it eliminates the risk of
      transfusion-transmitted infection or complications caused by the immune reaction.
      Increased platelet counts after repeated phlebotomy are commonly observed. This
      study was carried out to clarify the mechanism of increased platelets during
      preoperative autologous blood donation. Eleven patients of elective surgery in
      which is in good preoperative condition and there is no emergency were selected
      for this study. Blood cell counts, platelet size distribution(PDW, MPV, P-LCR)
      and serum concentration of erythropoietin(EPO), interleukin-3(IL-3) and
      interleukin-6(IL-6)were measured. A transient increase in platelet was seen in
      almost patients during preoperative autologous blood donation. No marked changes
      in platelet size distribution and serum concentration of EPO, IL-3 and IL-6.
      These results suggest that increased platelet counts during preoperative
      autologous blood donation might be caused by some specific cytokines related to
      megakaryocyte differentiation such as c-MPL ligand.

PMID- 9022347
TI  - [Study of serum thrombomodulin(TM) levels in patients with hyper- or hypo-
      thyroidism].
AB  - We studies a relationship between the serum levels of thrombomodulin(TM) and the
      thyroid functions. Serum TM levels were measured in 48 patients with Graves'
      disease, 17 patients with primary hypothyroidism, 7 patients with subacute
      thyroiditis, 5 patients with painless thyroiditis and 2 patients with systematic
      Refetoff syndrome. These patients did not have malignant tumor, kidney failure,
      or blood vessel injury. Control sera were obtained from 42 healthy subjects.
      Serum levels of TM in patients with untreated Graves' disease were significantly
      higher(p < 0.001) compared with those in controls. Serum levels of TM in patients
      with hypothyroidism were not significantly changed as compared with those of
      controls. There were a positive correlation between the serum levels of TM and
      FT3 as well as FT4. Serial determinations of the serum levels of TM and thyroid
      function(FT3, FT4 and TH) in patients with Graves' disease during treatment
      showed that both the serum levels of TM and thyroid hormones (FT3 and FT4)
      lowered progressively during treatment. After normalization of serum FT3 and FT4,
      the serum TM levels returned to normal. However, the serum levels of TM in
      patients with destructive thyroiditis and Refetoff syndrome were normal in spite
      of high serum levels of thyroid hormones. These data suggest that an increase in
      serum levels of TM is not the direct result of thyroid hormones themselves but is
      the result of the prolonged hypermetabolic state induced by their peripheral
      activities. Thyroid hormones may stimulate the synthesis or metabolism of TM on
      the surface of vascular endothelial cells in the patients with Graves' disease.

PMID- 9022348
TI  - [Detection of HPV-DNA in the various uterocervical lesion by the in situ
      polymerase chain reaction].
AB  - The causal association of human papilloma virus(HPV) with cervical cancer has
      been supported by multiple lines of evidence. Therefore, in the case of
      dysplasia, the presence of HPV-DNA should be detected and its subtypes
      identified. This is important in the determination of the prognosis for cervical
      disease. We reported a study in which the localization and types of HPV in
      cervical diseases was identified by in situ polymerase chain reaction(PCR), using
      biotin-labelled DNA probes. The in situ PCR, used by us was modified of Nuovo's
      method. We used biopsy materials of 18 CIN and 9 SCC cases(total 27 cases), all
      of which had been detected HPV-DNA by Southern blot hybridization, but not
      detected by in situ hybridization. A positive intranuclear reaction was detected
      in 13 of 18 CIN cases and 6 of 9 SCC cases(total 19 positive cases). Molecular
      biological techniques are the most reliable methods for detecting specific tumor
      genes and virus DNA. In situ hybridization has the advantage of enabling
      recognition of the cellular localization of the DNA in histologic specimens, but
      its sensitivity in inferior to the other techniques such as Southern blot, Dot
      blot and PCR. In situ PCR method possesses the advantages of both PCR and in situ
      hybridization in being highly sensitive and enabling visualization of the
      cellular localization of the DNA. In our present study, we succeeded to detect
      HPV-DNA in cervical biopsies of CIN and SCC cases by the in situ PCR.

PMID- 9022349
TI  - [Evaluation of one of the third generation reagents for anti-HCV antibody
      measurement in comparison with three second generation methods].
AB  - It is important to measure anti-HCV antibody(HCV.Ab) in blood to diagnose and
      treat viral hepatitis C patients. We evaluated one of the third generation
      reagents, Entymun-Test anti-HCV(Boehringer mannheim), which was developed to
      minimize false-positive reactions, and compared these results to findings
      obtained with three second generation tests for HCV.Ab. Coefficients of variation
      in the Entymum-Test assay were good(within-run, 1.1 approximately 1.8%; between
      run, 2.5 approximately 7.5%). Four interfering substances(bilirubin C, bilirubin
      F, lipid and hemoglobin) hardly affected the HCV.Ab measurement. The HCV.Ab
      indices of healthy donors(n = 61) were distributed below the cut-off
      index(C.O.I). Sensitivity of the third generation test was the same as that of
      second generation tests, calculated from the results of dilution tests. Index of
      the dilution test in the third generation test formed a plateau until four-fold
      dilution, but there was no prozone phenomenon. Among the third generation test
      and three second generation tests, the former had the lowest positive percentage
      in serum HCV.Ab. Moreover, findings of HCV-RNA agreed more with the results of
      the third generation test among the four tests. As a result, the third generation
      test appeared to minimize false-positive results and improve specificity.

PMID- 9022350
TI  - [The 69th congress of the Japanese Biochemistry Society. August 26-30, 1996.
      Sapporo City, Japan. Abstracts].

PMID- 9022351
TI  - Acute oral toxicity of the herbicide BUREX EKO in pheasants.
AB  - The aim of this study was to determine the acute LD50, clinical symptoms and
      pathological changes of acute BUREX EKO intoxication in pheasants according to
      OECD No 205. Medium lethal dose (LD50) of BUREX EKO in pheasant is 3.84 ml/kg
      body weight with the upper level of reliability 4.50 ml and lower level of
      reliability 3.27 ml/kg body weight. As far as the calculation to the effective
      substance is concerned it is 1077 mg of chloridazone per kg body weight with the
      interval of reliability from 919 to 1263 mg/kg body weight. Calculated the
      effective substance of chloridazone (3.84 ml is LD50 of BUREX EKO which contains
      1077 mg of chloridazone) BUREX EKO can be classified as the moderately toxic
      substance to pheasants. There were following clinical symptoms of the BUREX EKO
      intoxication in pheasants: apathy, drowsiness, incapability to move, ruffled
      feathers, slight diarrhoea, strenuous respiration, tonico-clonical cramps before
      death, decease with the head expressively bent rearwards. There was a relatively
      fast beginning of rigor mortis in dead pheasants. Pathologico-anatomical
      dissection of the pheasants obtained under conditions of acute intoxication did
      not reveal any changes on the organs of both experimental and control pheasants
      which would be immediately connected with the effect of the administered
      substance. Hyperaemia was recorded by histologico-pathological investigation of
      the liver and kidneys. No changes on the brain and intestine wall were recorded.

PMID- 9022352
TI  - Influence of microorganisms on the environmental fate of radionuclides.
AB  - Microorganisms have a significant influence on the environmental fate of
      radionuclides in aquatic and terrestrial ecosystems with a multiplicity of
      physico-chemical and biological mechanisms effecting changes in mobility and
      speciation. Physico-chemical mechanisms of removal include association with
      extracellular materials, metabolites and cell walls which are features of living
      and dead organisms. In living cells, some physico-chemical processes are
      reversible, influenced by metabolism and changing environmental conditions.
      Metabolism-dependent mechanisms of radionuclide immobilization include sulphide
      precipitation, transport and intracellular compartmentation and/or sequestration
      by proteins and peptides. In addition, chemical reduction to less soluble forms
      can result in immobilization. Microbial processes involved in radionuclide
      solubilization include autotrophic and heterotrophic leaching, and complexation
      by siderophores and other metabolites. Such mechanisms are important components
      of biogeochemical cycles for radionuclides and should be considered in any
      analyses of environmental radionuclide contamination. In addition, several
      microorganism-based biotechnologies are receiving interest as potential treatment
      methods.

PMID- 9022353
TI  - Analysing ancient DNA.
AB  - Much of what we know about extinct organisms comes from traits that are not
      preserved in the fossil record. Until recently, morphological analysis was the
      only tool available for scientists to determine relationships for extinct fossil
      organisms. We now know that "ancient' DNA can be preserved in the remains of
      extinct organisms. By targeting specific gene sequences, it may be possible to
      deduce biochemical characteristics and through sequence comparisons, to estimate
      the extent of evolutionary divergence. By comparing the amount and type of these
      changes, one could estimate how quickly some DNA 'evolves' relative to other
      segments, or which genes have the most flexibility or are more conserved over
      time. The compilation of these data would yield greater understanding of the
      physiology of extinct organisms and provide a much clearer picture of genetic
      change over time, and the mechanics behind 'evolution'.

PMID- 9022354
TI  - [Infections in neutropenic patients].

PMID- 9022355
TI  - [45th meeting of the American College of Cardiology. Orlando, 24-27 March 1996].

PMID- 9022356
TI  - [Navelbine (Vinorelbin)--current trends and results. Satellite symposium of the
      22nd German Cancer Congress. Berlin, 20 February 1996].

PMID- 9022357
TI  - [Tumor pain. Fentanyl TTS: a transdermal system for tumor pain therapy].

PMID- 9022358
TI  - [Present and future role of calcium antagonists in cardiac protection and
      treatment of coronary artery disease. Nice, 14-16 March 1996].

PMID- 9022359
TI  - [Therapy of senile osteoporosis. Osteoporosis symposium. Quarnbeck, 26-28 April
      1996].

PMID- 9022360
TI  - [Tamsulosin--the first selective alpha 1A-adrenergic receptor blocker in the
      treatment of BPH (benign prostatic hypertrophy)].

PMID- 9022361
TI  - [Alendronate (Fosamax 10 mg). The first amino-bisphosphate for the therapy of
      osteoporosis in postmenopausal women].

PMID- 9022362
TI  - [Chemotherapy of ovarian and breast cancer with Taxol].

PMID- 9022363
TI  - [Prospective study of safety, tolerability and contrasting effectiveness of a new
      dimer blood-isotonic contrast medium (Visipaque) on 35,033 patients. Lecture at
      the German Radiologic Congress 1996. Wiesbaden, 18 May 1996].

PMID- 9022364
TI  - [New trends in the management of heart failure. Symposium, Buhl, 5-7 February
      1993].

PMID- 9022365
TI  - [Drug premedication--routine or necessity?].

PMID- 9022366
TI  - [Myocardial insufficiency. Strategies in intensive care].

PMID- 9022367
TI  - [Peridural administration of opioids: state of the art].

PMID- 9022368
TI  - [PDE-III-inhibitors in intensive care. Strategy for the management of myocardial
      insufficiency].

PMID- 9022369
TI  - [Differential volume substitution therapy].

PMID- 9022370
TI  - [Strategies in premedication].

PMID- 9022371
TI  - German Congress on Anesthesiology. Yearly Meeting of the German Societyfor
      Anesthesiology and Intensive Care. Symposium: Sufentanil in anesthesia and
      intensive care. Nurnberg, 15 June 1994.

PMID- 9022372
TI  - [Quality assurance and quality management].

PMID- 9022373
TI  - [Topiramate: a broad-spectrum antiepileptic drug? Sixth meeting of the European
      Neurological Society. Den Haag, 8 June 1996].

PMID- 9022375
TI  - [Use of the spectrum of effects of gestagens in the practice of endocrinology.
      Jenapharm Symposium, Weimar, 21 March 1996].

PMID- 9022374
TI  - [Navelbine (Vinorelbin)--current trends and results. Satellite-Symposium on
      occasion of the 22nd German Cancer Congress. Berlin, 20 February 1996].

PMID- 9022376
TI  - [Alendronate (Fosamax 10 mg). The first amino-biphosphate for the treatment of
      women with postmenopausal osteoporosis].

PMID- 9022377
TI  - [Topotecan--a new principle of effectiveness in oncology. 4th Salzburg Symposium
      on Quality of Life. 15-17 December 1995].

PMID- 9022378
TI  - [News in the therapy of onychomycoses (Itraconazole)].

PMID- 9022379
TI  - [Modern topical corticoids--strong yet gentle to the skin].

PMID- 9022380
TI  - [Excessive immune reactions. Effective suppression with Loratadine].

PMID- 9022381
TI  - [Hydroxy pyridone as antimycotic agent].

PMID- 9022382
TI  - [Rhinoconjunctivitis. Highly selective therapy using topical H1-blockers].

PMID- 9022383
TI  - [Focusing on therapy of systemic mycoses].

PMID- 9022384
TI  - [Protection of the heart with beta blockaders].

PMID- 9022385
TI  - [Treatment of type II diabetics. The most neglected patient as well as the
      patient difficult to accept guidance].

PMID- 9022386
TI  - [Amiodarone in arrhythmia].

PMID- 9022387
TI  - [Avoiding compliance problems. Selection of the right drugs is important].

PMID- 9022388
TI  - [Management of dyspepsia. Management plan aimed at prevention of upper abdominal
      complaints].

PMID- 9022389
TI  - [Micrometastases and their relation to monoclonal antibodies].

PMID- 9022390
TI  - [Glaucoma. Current problems. Continuing education courses at the Ophthalmologic
      Clinic of the Eppendorf University Hospital, 9 December 1995].

PMID- 9022391
TI  - [Compliance determines therapeutic success in schizophrenia. Strategy in initial
      therapy].

PMID- 9022392
TI  - [Pharmacotherapy of alcoholism].

PMID- 9022393
TI  - [Topiramate--a new anti-epileptic agent].

PMID- 9022394
TI  - [Alpha-dihydroergocryptine; experiences--perspectives].

PMID- 9022395
TI  - [Nuclear medicine. Technetium-99m-Tetrofosmin--a reliable perfusion marker for
      myocardial scintigraphy].

PMID- 9022396
TI  - [Paget disease--an orphan of German medicine?].

PMID- 9022397
TI  - [Talperison in spasticity and and muscle rigidity].

PMID- 9022398
TI  - [ICD-10 (International Classification of Diseases): a new way with speed bumps?
      Discussed on the example of depression, anxiety and sleep disorders].

PMID- 9022399
TI  - [Topiramate: a broad-spectrum antiepileptic drug? Sixth meeting of the European
      Neurological Society. Den Haag, 8 June 1996].

PMID- 9022400
TI  - [Current aspects in the therapy of prostatic cancer].

PMID- 9022401
TI  - [Tacrolimus--a new perspective in kidney transplantation].

PMID- 9022402
TI  - [Short-term therapy of acute respiratory and ORL infections with Clarithromycin].

PMID- 9022403
TI  - [Cardiac insufficiency. Which therapeutic possibilities have long-term results].

PMID- 9022404
TI  - [Surfactant update. International Symposium on current aspects and developments].

PMID- 9022405
TI  - [LDL-reduction lowers mortality rates. Living longer with less cholesterol].

PMID- 9022406
TI  - [Bone transplantation: autologous material does not satisfy needs].

PMID- 9022407
TI  - [Cholesterol lowering--Quo vadis? WOS (West of Scotland)--study of pravastin--a
      milestone in the prevention of myocardial infarct?!].

PMID- 9022408
TI  - [A break-through in infarct prevention. WOS (West-of-Scotland)-study confirms
      effectiveness of early intervention using Pravastin].

PMID- 9022409
TI  - [Fosinopril in the cardiovascular management of elderly patients].

PMID- 9022410
TI  - [New events in the therapy of osteoporosis].

PMID- 9022411
TI  - [ACE-inhibitors: the indication spectrum grows wider].

PMID- 9022412
TI  - [Hypertension and stroke. With special emphasis on antihypertensive therapy].

PMID- 9022413
TI  - [Cancer therapy facing radical change: ambulatory care or partial
      hospitalization, whenever possible?].

PMID- 9022414
TI  - [Therapeutic management of asthma: what is safe? What is new? What is being done
      incorrectly].

PMID- 9022415
TI  - [Navelbine (Vinorelbin)--current trends and results. Satellite Symposium on
      occasion of the 22nd German Cancer Congress. Berlin, 20 February 1996].

PMID- 9022416
TI  - [Oncology--a common language, new perspectives. Lilly Oncology Global Medical
      Conference, Indianapolis, 1996].

PMID- 9022417
TI  - [Growth hormone for severely burnt patients].

PMID- 9022418
TI  - Out of hours primary care.

PMID- 9022419
TI  - Epilepsy: getting the diagnosis right.

PMID- 9022420
TI  - Lack of oats toxicity in coeliac disease.

PMID- 9022421
TI  - Hysterectomy: will it pay the bills in 2007?

PMID- 9022422
TI  - Drinking before sedation.

PMID- 9022423
TI  - Non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary
      disease.

PMID- 9022424
TI  - Don't treat shackled patients.

PMID- 9022425
TI  - Court hears assisted suicide debate.

PMID- 9022426
TI  - Hormone scandal hits France.

PMID- 9022427
TI  - Baby milk companies accused of breaching marketing code.

PMID- 9022428
TI  - Retrospective study of concussive convulsions in elite Australian rules and rugby
      league footballers: phenomenology, aetiology, and outcome.
AB  - OBJECTIVES: To study the ictal phenomenology, aetiology, and outcome of
      convulsions occurring within seconds of impact in violent collision sport.
      DESIGN: Retrospective identification of convulsions associated with concussive
      brain injury from case records from medical officers of football clubs over a 15
      year period. SUBJECTS: Elite Australian rules and rugby league footballers. MAIN
      OUTCOME MEASURES: Neuroimaging studies, electroencephalography,
      neuropsychological test data, and statistics on performance in matches to
      determine presence of structural or functional brain injury. Clinical follow up
      and electroencephalography for evidence of epilepsy. RESULTS: Twenty two cases of
      concussive convulsions were identified with four events documented on television
      videotape. Convulsions began within 2 seconds of impact and comprised an initial
      period of tonic stiffening followed by myoclonic jerks of all limbs lasting up to
      150 seconds. Some asymmetry in the convulsive manifestations was common, and
      recovery of consciousness was rapid. No structural or permanent brain injury was
      present on clinical assessment, neuropsychological testing, or neuroimaging
      studies. All players returned to elite competition within two weeks of the
      incident. Epilepsy did not develop in any player over a mean (range) follow up of
      3.5 (1-13) years. CONCLUSIONS: These concussive or impact convulsions are
      probably a non-epileptic phenomenon, somewhat akin to convulsive syncope. The
      mechanism may be a transient traumatic functional decerebration. In concussive
      convulsions the outcome is universally good, antiepileptic treatment is not
      indicated, and prolonged absence from sport is unwarranted.

PMID- 9022429
TI  - Popularity of less frequent follow up for breast cancer in randomised study:
      initial findings from the hotline study.
AB  - OBJECTIVE: To compare the experiences of patients with breast cancer who were
      conventionally monitored with those in whom routine follow up was restricted to
      the time of mammography. DESIGN: Randomisation to conventional schedule of clinic
      visits or to visits only after mammography. Both cohorts received identical
      mammography and were invited to telephone for immediate appointments if they
      detected symptoms. SETTING: Combined breast clinic, Chelsea and Westminster
      Hospital. SUBJECTS: 211 eligible outpatients with a history of breast cancer.
      MAIN OUTCOME MEASURES: Acceptability of randomisation, interim use of telephone
      and general practitioner, satisfaction with allocation to follow up. RESULTS: Of
      211 eligible patients, 196 (93%) opted for randomisation in the study. Of these,
      55 were under 50 years, 78 were diagnosed fewer than five years before, 90 had
      stage T2-4 tumours, and 71 had involved axillary nodes. Patients who did not
      participate were more likely to be under 50 years, to be two to five years after
      diagnosis, and to have had aggressive primary disease. Twice as many patients in
      both groups expressed a preference for reducing rather than increasing follow up.
      No increased use of local practitioner services or telephone triage was apparent
      in the cohort randomised to less frequent follow up by specialists. CONCLUSIONS:
      Reducing the frequency of routine follow up has so far proved popular among
      patients with breast cancer at standard risk in this cohort. A multicentre study
      is needed to determine the effectiveness and cost-effectiveness of routine follow
      up with respect to disease outcomes.

PMID- 9022430
TI  - Weight loss in people with Alzheimer's disease: a prospective population based
      analysis.

PMID- 9022431
TI  - Prevalence of hepatitis C antibodies among healthcare workers of two teaching
      hospitals. Who is at risk?

PMID- 9022432
TI  - Severe persistent visual field constriction associated with vigabatrin.

PMID- 9022433
TI  - Observational study of a general practice out of hours cooperative: measures of
      activity.
AB  - OBJECTIVE: To evaluate an out of hours cooperative of general practitioners
      compared with a deputising service. DESIGN: Observational study of two services
      in overlapping geographical areas. SETTING: A general practice cooperative in
      Kensington, Chelsea, and Westminster and a deputising service operating in that
      area and the neighbouring area of Brent and Harrow. SUBJECTS: All patients
      contacting a doctor at either service in an eight week period beginning 1
      September 1995. MAIN OUTCOME MEASURES: Patients' age and sex; rates of home
      visiting, telephone advice, and attendance at a primary centre; hospital
      admission rates; prescribing rates; times of patient cells; and response times.
      RESULTS: Data were collected on 5812 patient contacts. Doctors from the
      cooperative visited 32.0% (1253/ 3920) of patients, offered telephone advice to
      57.8% (2267), and saw 7.1% (278) of patients at the primary care centre. By
      contrast, the deputising service visited 76.3% (1444/1892) of patients and gave
      telephone advice to 19.3% (365). Doctors from the cooperative prescribed drugs to
      fewer patients (37.6%; 1473/3915) than did the deputising service (51.7%;
      941/1821) (odds ratio 0.56 (95% confidence interval 0.50 to 0.63) adjusted for
      age and sex) and admitted 8.7% (339/ 3888) of patients to hospital compared with
      6.8% (128/1889) from the deputising service (odds ratio 1.30 (1.05 to 1.61)
      adjusted for age and sex). Response times for the deputising service were faster
      (median time to visit 65 minutes) than for the cooperative (median time to visit
      75 minutes) but the time to first contact with a doctor was shorter for the
      cooperative because most people initially received telephone advice. CONCLUSIONS:
      The cooperative in this study dealt with patient contacts very differently from
      the way the deputising service dealt with contacts, fewer patients being visited
      and fewer receiving prescriptions. The data presented enable other out of hours
      services to compare their own performance using a standard data collection and
      analysis program.

PMID- 9022434
TI  - Comparison of out of hours care provided by patients' own general practitioners
      and commercial deputising services: a randomised controlled trial. I: The process
      of care.
AB  - OBJECTIVE: To compare the process of out of hours care provided by general
      practitioners from patients' own practices and by commercial deputising services.
      DESIGN: Randomised controlled trial. SETTING: Four urban areas in Manchester,
      Salford, Stockport, and Leicester. SUBJECTS: 2152 patients who requested out of
      hours care, and 49 practice doctors and 183 deputising doctors (61% local
      principals) who responded to those requests. MAIN OUTCOME MEASURES: Response to
      call, time to visit, prescribing, and hospital admissions. RESULTS: 1046 calls
      were dealt with by practice doctors and 1106 by deputising doctors. Practice
      doctors were more likely to give telephone advice (20.2% v 0.72% of calls) and to
      visit more quickly than deputising doctors (median delay 35 minutes v 52
      minutes). Practice doctors were less likely than deputising doctors to issue a
      prescription (56.1% v 63.2% of patients) or to prescribe an antibiotic (43.7% v
      61.3% of prescriptions issued) and more likely to prescribe genetic drugs (58.4%
      v 32.1% of drugs prescribed), cheaper drugs (mean cost per prescription pounds
      3.28 v pounds 5.04), and drugs in a predefined out of hours formulary (49.8% v
      41.1% of drugs prescribed). There was no significant difference in the number of
      hospital admissions. CONCLUSIONS: By contrast with practice doctors, deputising
      doctors providing out of hours care less readily give telephone advice, take
      longer to visit at home, and have patterns of prescribing that may be less
      discriminating.

PMID- 9022435
TI  - Comparison of out of hours care provided by patients' own general practitioners
      and commercial deputising services: a randomised controlled trial. II: The
      outcome of care.
AB  - OBJECTIVE: To compare the outcome of out of hours care given by general
      practitioners from patients' own practices and by commercial deputising services.
      DESIGN: Randomised controlled trial. SETTING: Four urban areas in Manchester,
      Salford, Stockport, and Leicester. SUBJECTS: 2152 patients who requested out of
      hours care, and 49 practice doctors and 183 deputising doctors (61% local
      principals in general practice) who responded to the requests. MAIN OUTCOME
      MEASURES: Health status outcome, patient satisfaction, and subsequent health
      service use. RESULTS: Patients seen by deputising doctors were less satisfied
      with the care they received. The mean overall satisfaction score for practice
      doctors was 70.7 (95% confidence interval 68.1 to 73.2) and for deputising
      doctors 61.8 (59.9 to 63.7). The greatest difference in satisfaction was with the
      delay in visiting. There were no differences in the change in health or overall
      health status measured 24 to 120 hours after the out of hours call or subsequent
      use of the health service in the two groups. CONCLUSIONS: Patients are more
      satisfied with the out of hours care provided by practice doctors than that
      provided by deputising doctors. Organisation of doctors into large groups may
      produce lower levels of patient satisfaction, especially when associated with
      increased delays in the time taken to visit. There seem to be no appreciable
      differences in health outcome between the two types of service.

PMID- 9022436
TI  - Reliability and validity of a new measure of patient satisfaction with out of
      hours primary medical care in the United Kingdom: development of a patient
      questionnaire.
AB  - OBJECTIVE: To develop a reliable, valid measure of patient satisfaction with out
      of hours care suitable for large scale service evaluation. DESIGN: Focus group
      meetings and semistructured interviews with patients to identify issues of
      importance to patients and possible questionnaire items; interviews and two pilot
      studies to test and identify new questionnaire items; modification or removal of
      items to eliminate ambiguity and reduce non-response and skewed responses;
      questionnaire survey of out of hours care. SETTING: Greater Manchester and
      Leicester. SUBJECTS: 11 general practice patients participated in the focus
      groups and 28 in the semistructured interviews; 41 in the preliminary interviews;
      41 and 378 in the postal pilots; and 1466 in the survey of out of hours care.
      RESULTS: A 32 item questionnaire was developed. Component analysis indicated
      seven scales (satisfaction with communication and management, doctor's attitude,
      continuity of care, delay until visit, access to out of hours care, initial
      contact person, telephone advice) related to overall satisfaction and containing
      issues identified as important to patients. Levels of reliability were
      satisfactory, Cronbach's alpha correlation coefficient exceeding 0.60 for all
      scales. CONCLUSION: A reliable, valid measure of patient satisfaction has been
      developed, suitable for large scale evaluation of out of hours care.

PMID- 9022437
TI  - Nurse telephone triage in out of hours primary care: a pilot study. South
      Wiltshire Out of Hours Project (SWOOP) Group.

PMID- 9022438
TI  - Changing the pattern out of hours: a survey of general practice cooperatives.

PMID- 9022439
TI  - Paediatric anaesthesia.

PMID- 9022440
TI  - Role of molecular cell biology in understanding disease.
AB  - Molecular techniques have revolutionised our knowledge of cell and tissue
      function in both health and disease. We already have new and powerful treatments
      based on an understanding of communication between cells by messenger molecules
      called cytokines. Furthermore, there is great therapeutic promise in defining
      molecules which regulate cell adhesion, motility, proliferation, survival, and
      death. Rational manipulation of cell and tissue function for therapeutic ends may
      be much closer than you think.

PMID- 9022441
TI  - Prevalence of concomitant disease in patients with iron deficiency anaemia.

PMID- 9022442
TI  - Diabetes and hypertension in Britain's ethnic minorities: implications for the
      future of renal services.
AB  - Diabetes and hypertension are much more prevalent among Britain's 2.5 million
      Asian and African-Caribbean population than among the white population and are
      major contributors to end stage renal failure. Asians and African-Caribbeans have
      threefold to fourfold higher acceptance rates on to renal replacement therapy
      than white people, and in some districts they comprise up to half of all patients
      receiving such treatment. Their greater need for renal replacement treatment is
      accompanied by difficulties of tissue matching in cross racial transplants and a
      shortage of donor organs. The aging of ethnic minority populations will increase
      local need for renal services significantly. Measures to control diabetes,
      hypertension, and secondary complications in Asian and African-Caribbean
      communities will contribute both to safeguarding health and to economies in
      spending on renal services. Education about diabetes and hypertension,
      modification of behavioural risk factors, early diagnosis, effective glycaemic
      and blood pressure control, and early referral for signs of renal impairment are
      essential preventive measures. Primary and community health care professionals
      have a critical role to play here.

PMID- 9022443
TI  - Association of use of a log book and experience as a preregistration house
      officer: interview survey.
AB  - OBJECTIVE: To determine whether use of a log book improved the experiences of
      preregistration house officers. DESIGN: Confidential questionnaire and interview
      survey of preregistration house officers carried out as part of University of
      London inspection process. MEASURES: Preregistration house officers were asked to
      rate educational and pastoral elements of their posts and about the use made of
      previously distributed log books. SUBJECTS AND SETTING: Preregistration house
      officers in North Thames. RESULTS: The incumbents of 535 of 560 (95%)
      preregistration house officer posts in the region were surveyed between June 1994
      and July 1995, 490 by questionnaire and interview, 45 by questionnaire alone.
      House officers who had discussed the log book with their consultant expressed
      more satisfaction with their induction, consultant supervision and feedback, and
      formal and informal education and were more likely to recommend their job to a
      friend. CONCLUSION: Preregistration house officers who had discussed the log book
      with their consultant expressed more satisfaction with the educational elements
      of their jobs. The structured discussion with their consultant about the job and
      their performance seemed to make the difference.

PMID- 9022444
TI  - Commentary: educational initiatives deserve randomised controlled trials.

PMID- 9022445
TI  - Funding the NHS. A little local difficulty?
AB  - The media have been full of reports of crisis in the NHS. Although national
      analyses suggest that the NHS should be able to cope within the increases in
      spending it has been given, local pressures can leave parts of the service
      struggling. Firstly, the change to allocation of funds on the basis of population
      needs has meant that some authorities and trusts have had effective cuts in their
      budgets, requiring them to trim services. Secondly, the government's insistence
      on an annual 3% increase in efficiency may have resulted in authorities taking
      short term measures that actually decrease efficiency in the long term. Thirdly,
      health authorities have had to bear the costs of national targets such as
      reducing waiting lists and junior doctors' hours as well as local problems such
      as higher numbers of mentally disordered offenders. However, all these factors
      can be controlled by national or local management and so their impact is not
      inevitable.

PMID- 9022446
TI  - Data are not now collected by ethnic group in South Africa.

PMID- 9022447
TI  - Dealing with patients with HIV infection. Isolation is impractical and
      unnecessary.

PMID- 9022448
TI  - Dealing with patients with HIV infection. Such bigotry should not have been
      published.

PMID- 9022449
TI  - Dealing with patients with HIV infection. Eliminating poverty and ignorance is
      the solution.

PMID- 9022450
TI  - Dealing with patients with HIV infection. Few authors have the courage to stand
      up and be counted.

PMID- 9022451
TI  - Having some lifesaving skills must be better than having none.

PMID- 9022452
TI  - Clinical effects of anticoagulants in suspected acute myocardial infarction.
      Adding heparin seems justified.

PMID- 9022453
TI  - Clinical effects of anticoagulants in suspected acute myocardial infarction.
      Reduced intensity of anticoagulation may be indicated.

PMID- 9022454
TI  - Clinical effects of anticoagulants in suspected acute myocardial infarction. Use
      of anticoagulants in suspected acute myocardial infarction in Europe varies.

PMID- 9022455
TI  - Case for lack of metabolic effects has not been made.

PMID- 9022456
TI  - Authors' arguments about infertility services were based on a misunderstanding.

PMID- 9022457
TI  - Investigations to diagnose cause of dizziness in elderly people. Clinical
      assessment in the surgery is not adequate.

PMID- 9022458
TI  - Investigations to diagnose cause of dizziness in elderly people. Algorithm should
      ask whether patient is taking drugs that may cause dizziness.

PMID- 9022459
TI  - Implementing guidance on hepatitis B for applicants to medical school is time
      consuming.

PMID- 9022460
TI  - Predicting adverse cardiac events after myocardial infarction and thrombolysis.
      External validity of authors' conclusions is doubtful.

PMID- 9022461
TI  - Predicting adverse cardiac events after myocardial infarction and thrombolysis.
      Study does not justify replacement of exercise testing with radionuclide imaging.

PMID- 9022462
TI  - Varicella vaccine in pregnancy. Testing should be offered to women without a
      history of chickenpox.

PMID- 9022463
TI  - Varicella vaccine in pregnancy. Varicella zoster immunoglobulin should be given
      after exposure to the virus.

PMID- 9022464
TI  - Methods of surveying patients' satisfaction. Patients should help decide the
      wording and design of questionnaires.

PMID- 9022465
TI  - Methods of surveying patients' satisfaction. Patients' satisfaction is based
      firmly on their expectations.

PMID- 9022466
TI  - Deprivation payments to general practitioners. Scores are calculated relative to
      national average.

PMID- 9022467
TI  - Deprivation payments to general practitioners. Payments bear little relation to
      practices' actual level of deprivation.

PMID- 9022468
TI  - Deprivation payments to general practitioners. Standard of service provided by
      practice should also be taken into account.

PMID- 9022470
TI  - Deprivation payments to general practitioners. New group has been formed to try
      to bring about change.

PMID- 9022469
TI  - Deprivation payments to general practitioners. Scores should be based on
      enumeration districts, and payments should be phased in gradually.

PMID- 9022471
TI  - Microbiologists are available 24 hours a day to give advice.

PMID- 9022472
TI  - Decision to resect an adrenal mass depends on size of mass and age of patient.

PMID- 9022473
TI  - Pessimistic views of the NHS. Doctors should stop seeing themselves as victims.

PMID- 9022474
TI  - Pessimistic views of the NHS. Joint commissioning is the way forward.

PMID- 9022475
TI  - Gulf war illness.

PMID- 9022476
TI  - Outbreaks of E coli.

PMID- 9022477
TI  - Pig transplants postponed.

PMID- 9022478
TI  - Cervical carotid or vertebral artery dissection.

PMID- 9022479
TI  - Antiphospholipid (Hughes') syndrome.

PMID- 9022480
TI  - Time to look again at sight tests.

PMID- 9022481
TI  - London's mental health services in crisis.

PMID- 9022482
TI  - New authority to monitor xenotransplantation experiments.

PMID- 9022483
TI  - Hay fever drug to be banned by the FDA.

PMID- 9022484
TI  - E coli inquiry calls for stricter laws on selling meat.

PMID- 9022485
TI  - French patient contracts AIDS from surgeon.

PMID- 9022486
TI  - US medicine marches slowly toward UK solution.

PMID- 9022487
TI  - Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women
      with recurrent miscarriage associated with phospholipid antibodies (or
      antiphospholipid antibodies)
AB  - OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads
      to a higher rate of live births than that achieved with low dose aspirin alone in
      women with a history of recurrent miscarriage associated with phospholipid
      antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin
      antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial.
      SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median
      age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4
      (range 3-15)) and persistently positive results for phospholipid antibodies.
      INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000
      U of unfractionated heparin subcutaneously 12 hourly. All women started treatment
      with low dose aspirin when they had a positive urine pregnancy test. Women were
      randomly allocated an intervention when fetal heart activity was seen on
      ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks'
      gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments.
      RESULTS: There was no significant difference in the two groups in age or the
      number and gestation of previous miscarriages. The rate of live births with low
      dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies)
      with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to
      8.10)). More than 90% of miscarriages occurred in the first trimester. There was
      no difference in outcome between the two treatments in pregnancies that advanced
      beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were
      delivered before 37 weeks' gestation. Women randomly allocated aspirin and
      heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6%
      to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly
      higher rate of live births in women with a history of recurrent miscarriage
      associated with phospholipid antibodies than that achieved with aspirin alone.

PMID- 9022488
TI  - Variations in use of cardiology services in a health authority: comparison of
      coronary artery revascularisation rates with prevalence of angina and coronary
      mortality.
AB  - OBJECTIVE: To explore the relation between rates of coronary artery
      revascularisation and prevalence of angina to assess whether use of health
      services reflects need. DESIGN: Prevalence of angina symptoms determined by
      postal questionnaire on 16750 subjects (18 to 94 years). Comparison of data on
      use of coronary artery revascularisation with prevalence of symptoms and
      mortality from coronary heart disease. SETTING: Health authority with population
      of 530000. SUBJECTS: Patients admitted to hospital for coronary heart disease;
      patients who died; and patients undergoing angiography, angioplasty, or coronary
      artery bypass graft. Cohort of 491 people with symptoms from survey. MAIN OUTCOME
      MEASURES: Pearson's product moment correlation coefficients for relation between
      variables. RESULTS: Overall, 4.0% (95% confidence interval 3.7% to 4.4%) of
      subjects had symptoms. Prevalences varied widely between electoral wards and were
      positively associated with Townsend score (r = 0.79; P < 0.001), as was
      mortality, but the correlation between admission rates and Townsend score was
      less clear (r = 0.47; P < 0.01). Revascularisation rate and Townsend score were
      not associated. The ratio of revascularisation to number experiencing symptoms
      was inversely related to Townsend score (r = 0.67; P < 0.001). The most deprived
      wards had only about half the number of revascularisations per head of population
      with angina than did the more affluent wards. In affluent wards 11% (13/116) of
      those with symptoms had coronary angiograms compared with only 4% (9/216) in
      poorer wards (chi 2 = 4.96; P = 0.026). Townsend score also inversely correlated
      with revascularisations per premature death from coronary heart disease (r =
      0.55; P < 0.01) and revascularisations per admission for myocardial infarction (r
      = 0.47; P < 0.01). CONCLUSION: The use of interventional cardiology services is
      not commensurate with need, thus exhibiting the inverse care law.

PMID- 9022489
TI  - Relation between bed use, social deprivation, and overall bed availability in
      acute adult psychiatric units, and alternative residential options: a cross
      sectional survey, one day census data, and staff interviews.
AB  - OBJECTIVES: To examine the relation between bed use, social deprivation, and
      overall bed availability in acute adult psychiatric units and to explore the
      range of alternative residential options. DESIGN: Cross sectional survey,
      combined with one day census data; ratings by and interviews with staff;
      examination of routine data sources. SETTINGS: Nationally representative sample
      of acute psychiatric units. SUBJECTS: 2236 patients who were inpatients on census
      day. MAIN OUTCOME MEASURES: Bed occupancy levels, judged need for continuing
      inpatient care, reasons preventing discharge, scores on the Health of the Nation
      outcome scales. RESULTS: Bed occupancy was related to social deprivation and
      total availability of acute beds (r = 0.66, 95% confidence interval 0.19 to 0.88,
      F = 8.72, df = 2.23; P = 0.002). However, 27% (603/2215) of current inpatients
      (61% (90/148) of those with stays of > 6 months) were judged not to need
      continuing admission. The major reasons preventing discharge were lack of
      suitable accommodation (37% (176/482) of patients in hospital < 6 months v 36%
      (31/86) of those in hospital > 6 months); inadequate domiciliary based community
      support (23% (113) v 9% (8)); and lack of long term rehabilitation places (21%
      (100) v 47% (40)). Scores on the Health of the Nation outcome scale were
      generally consistent with these staff judgments. CONCLUSIONS: The shortage of
      beds in acute psychiatric units is related to both social deprivation and the
      overall availability of acute beds. Patients currently inappropriately placed on
      acute admission wards should be relocated into more suitable accommodation,
      either in hospital or in the community. A range of provisions is required; simply
      providing more acute beds is not the answer.

PMID- 9022491
TI  - Evaluating the reliability of causes of death in published clinical research.

PMID- 9022490
TI  - Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with
      necropsy follow up.
AB  - OBJECTIVE: To investigate the contribution of neuroleptic drugs to cognitive
      decline in dementia. DESIGN: Two year prospective, longitudinal study consisting
      of interviews every four months, with necropsy follow up. SETTING: Community
      settings in Oxfordshire. SUBJECTS: 71 subjects with dementia, initially living at
      home with informant. MAIN OUTCOME MEASURES: Cognitive function (score from
      expanded minimental state examination); behavioural problems (physical
      aggression, hallucinations, persecutory ideas, and disturbance of diurnal
      rhythm); and postmortem neuropathological assessment (cortical Lewy body
      pathology). RESULTS: The mean (SE) decline in cognitive score in the 16 patients
      who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v
      9.3 (1.3), P = 0.002). An increased rate of decline was also associated with
      aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of
      neuroleptics and severity of persecutory ideas were independently associated with
      more rapid cognitive decline when all other variables were adjusted for. The
      start of neuroleptic treatment coincided with more rapid cognitive decline:
      median rate of decline was 5 (interquartile range 8.5) points per year before
      treatment and 11 (12) points per year after treatment (P = 0.02). Cortical Lewy
      body pathology did not account for association between neuroleptic use and more
      rapid decline. CONCLUSIONS: Neuroleptic drugs that are sometimes used to treat
      behavioural complications of dementia may worsen already poor cognitive function.
      Randomised controlled trials are needed to confirm a causal relation.

PMID- 9022492
TI  - Case-control study of stroke and the quality of hypertension control in north
      west England.
AB  - OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension
      control in routine general practice across an entire health district. DESIGN:
      Population based matched case-control study. SETTING: East Lancashire Health
      District with a participating population of 388,821 aged < or = 80. SUBJECTS:
      Cases were patients under 80 with their first stroke identified from a population
      based stroke register between 1 July 1994 and 30 June 1995. For each case two
      controls matched with the case for age and sex were selected from the same
      practice register. Hypertension was defined as systolic blood pressure > or = 160
      mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two
      occasions within any three month period or any history of treatment with
      antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and
      quality of control of hypertension assessed by using the mean blood pressure
      recorded before stroke) and odds ratios of stroke (derived from conditional
      logistic regression). RESULTS: Records of 267 cases and 534 controls were
      examined; 61% and 42% of these subjects respectively were hypertensive. Compared
      with non-hypertensive subjects hypertensive patients receiving treatment whose
      average pre-event systolic blood pressure was controlled to < 140 mm Hg had an
      adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those
      fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or
      poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds
      ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure
      were similar; both were independent of initial pressures before treatment. Around
      21% of strokes were thus attributable to inadequate control with treatment, or 46
      first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of
      stroke was clearly related to quality of control of blood pressure with
      treatment. In routine practice consistent control of blood pressure to below
      150/90 mm Hg seems to be required for optimal stroke prevention.

PMID- 9022493
TI  - Information needed to decide about cardiovascular treatment in primary care.
AB  - There is growing consensus that treatment of cardiovascular risks should be based
      on multiple rather than single factors and on absolute rather than relative
      risks. Thresholds for treatment should reflect the level of absolute risk at
      which the benefits and hazards of treating outweigh the benefits and hazards of
      not treating. Once a decision has been made to initiate a treatment programme,
      clinicians need to know the patient's absolute risk. At this level of risk do the
      benefits of treatment outweigh the hazards? Given this information, which
      treatment option does the patient prefer? Using cardiovascular disease as an
      example, I review some measures that assist decision making in primary care.
      Practice guidelines should routinely include accessible presentation of treatment
      outcomes on benefit, hazard, and costs for a range of absolute risks. These
      measures enable patients and their doctors to weigh the pros and cons of
      treatment in their particular circumstances.

PMID- 9022494
TI  - Women's need for information before attending genetic counselling for familial
      breast or ovarian cancer: a questionnaire, interview, and observational study.
AB  - OBJECTIVES: To describe women's information needs prior to genetic counselling
      for familial breast or ovarian cancer. DESIGN: Prospective study including
      semistructured telephone interviews before genetic counselling, observations of
      consultations, completion of postal questionnaires, and face-to face interviews
      within two months of counselling. SUBJECTS: 46 women attending genetic
      counselling for familial breast or ovarian cancer. MAIN OUTCOME MEASURES:
      Subjects' understanding of process and content of genetic counselling before
      attending and attitudes about their preparation for the counselling session.
      RESULTS: Although all women interviewed before the clinic expected to discuss
      their risk of developing cancer and risk management options, there was evidence
      of a lack of knowledge about the process and content of genetic counselling, 17
      (37%) women said they did not know what else would happen. Most women interviewed
      after counselling viewed it positively, but 26 (65%) felt they had been
      inadequately prepared and 11 (28%) felt that their lack of preparation meant that
      they could not be given an accurate estimation of their risk of cancer.
      CONCLUSIONS: Some women felt that they did not obtain optimum benefit from
      genetic counselling because they were inadequately prepared for it. We suggest
      that cancer family history clinics should provide women with written information
      about the process and content of genetic counselling before their clinic
      attendance.

PMID- 9022495
TI  - Screening for asymptomatic colorectal cancer.

PMID- 9022496
TI  - Carotid dissection causing stroke in a child with migraine.

PMID- 9022497
TI  - Systemic lupus erythematosus [clinical inference].

PMID- 9022498
TI  - Funding the NHS. Is the NHS sustainable?
AB  - The survival of the NHS lies largely in the hands of government, and this article
      suggests steps that it should take to deal with pressures on the NHS in terms of
      funding, managing efficiency, and demands. Changes to the system of funding may
      be unfeasible, but management could be improved by research to allow greater
      understanding of the local effects of national policies. Alternatively health
      authorities could be given more freedom to manage funds, although this would have
      to be accompanied by stiff sanctions for those who failed. Demand could be
      contained by strengthening policies to ensure that new technologies are cost
      effective. The government could try to reduce demands arising from increased
      expectations by encouraging informed public debate about priorities and
      influencing the availability of private health care. All these efforts should be
      guided by the values underpinning the NHS, which should be debated and decided
      collectively and confirmed in a new charter for NHS's 50th anniversary in 1998.

PMID- 9022499
TI  - Suspension of nurse who gave drug on consultant's instructions. What has happened
      to clinical freedom?

PMID- 9022500
TI  - Suspension of nurse who gave drug on consultant's instructions. Doctor and nurse
      were subjected to "macho management".

PMID- 9022501
TI  - Suspension of nurse who gave drug on consultant's instructions. Ethics of giving
      drug treatment covertly needs further discussion.

PMID- 9022502
TI  - Suspension of nurse who gave drug on consultant's instructions. Engage staff in
      programmes to raise ethical awareness.

PMID- 9022503
TI  - Suspension of nurse who gave drug on consultant's instructions. Over a third of
      psychiatrists had given a drug surreptitiously or lied about a drug.

PMID- 9022504
TI  - Suspension of nurse who gave drug on consultant's instructions. Concealed
      administration of drug treatment may represent thin end of the wedge.

PMID- 9022505
TI  - Criticism of study of childhood leukaemia near French nuclear reprocessing plant
      is unfounded.

PMID- 9022506
TI  - Study design and nature of diabetes may explain findings of Finnish study.

PMID- 9022507
TI  - Data on eligibility for thrombolytic treatment can indeed be generalised.

PMID- 9022508
TI  - Promoting health in prisons. NHS would provide an inferior service.

PMID- 9022509
TI  - Promoting health in prisons. Prison service for England and Wales has been
      designated a WHO collaborating centre.

PMID- 9022510
TI  - Do fetuses feel pain? Can fetal suffering be excluded beyond reasonable doubt?

PMID- 9022511
TI  - Do fetuses feel pain? We should give them the benefit of the doubt.

PMID- 9022512
TI  - Computerised automatic warnings about drug interactions are now available.

PMID- 9022513
TI  - Differences in mortality between African Caribbean and European people with non
      insulin dependent diabetes. Authors' method of assigning ethnic group was wrong.

PMID- 9022514
TI  - Differences in mortality between African Caribbean and European people with non
      insulin dependent diabetes. Lack of ethnic differences in renal complications of
      diabetes is puzzling.

PMID- 9022515
TI  - Differences in mortality between African Caribbean and European people with non
      insulin dependent diabetes. Absolute risk of coronary heart disease is not low in
      African Caribbeans.

PMID- 9022516
TI  - IgA content of immunoglobulin preparation was overstated.

PMID- 9022517
TI  - High voltage power lines and risk of cancer. Conclusions are unjustified.

PMID- 9022518
TI  - Doctors, nurses, and terminal care. Nurses need to accept more responsibility,
      and doctors need better training.

PMID- 9022519
TI  - Doctors, nurses, and terminal care. Medical students in Cambridge do two nursing
      shifts.

PMID- 9022520
TI  - Treating shackled patients. Patient's best interest in receiving most appropriate
      treatment without delay must prevail.

PMID- 9022521
TI  - Treating shackled patients. Superficiality of editorial gives rise to more anger
      than do shackles.

PMID- 9022522
TI  - Treating shackled patients. Assumption that shackles will not be used should be
      ignored only in exceptional cases.

PMID- 9022523
TI  - Prediction of total subcutaneous abdominal, intraperitoneal, and retroperitoneal
      adipose tissue masses in men by a single axial magnetic resonance imaging slice.
AB  - To develop a simplified but accurate method for determining the masses of various
      abdominal adipose tissue compartments, we studied the predictive value of masses
      of intraperitoneal, retroperitoneal, and subcutaneous abdominal adipose tissue
      determined on single axial abdominal magnetic resonance imaging (MRI) slices
      taken at various intervertebral levels from the 12th thoracic to 1st sacral
      vertebra (identified on a sagittal section) for the respective total masses of
      each compartment calculated from contiguous 10-mm thick MRI slices covering the
      entire abdomen in 49 men (26 without diabetes and 23 with non-insulin-dependent
      diabetes mellitus). The MRI slice at the intervertebral level between the lumbar
      (L) 2 and 3 vertebrae showed the highest and most consistent predictive value for
      all three compartments (R2 = 0.85 for all). Furthermore, compared with other
      intervertebral levels, the L2-L3 level had a higher amount of intraperitoneal and
      retroperitoneal adipose tissue mass. We conclude that determining the masses of
      various abdominal adipose tissue compartments at the L2-L3 intervertebral level
      by MRI is an acceptably reliable and accurate method for studying abdominal
      adiposity in men.

PMID- 9022524
TI  - The effect of aspartame as part of a multidisciplinary weight-control program on
      short- and long-term control of body weight.
AB  - This study investigated whether the addition of the high-intensity sweetener
      aspartame to a multidisciplinary weight-control program would improve weight loss
      and long-term control of body weight. One hundred sixty-three obese women were
      randomly assigned to consume or to abstain from aspartame-sweetened foods and
      beverages during 16 wk of a 19-wk weight-reduction program (active weight loss),
      a 1-y maintenance program, and a 2-y follow-up period. Women in both treatment
      groups lost approximately 10% of initial body weight (10 kg) during active weight
      loss. Among women assigned to the aspartame-treatment group, aspartame intake was
      positively correlated with percentage weight loss during active weight loss (r =
      0.32, P < 0.01). During maintenance and follow-up, participants in the aspartame
      group experienced a 2.6% (2.6 kg) and 4.6% (4.6 kg) regain of initial body weight
      after 71 and 175 wk, respectively, whereas those in the no-aspartame group gained
      an average of 5.4% (5.4 kg) and 9.4% (9.4 kg), respectively. The aspartame group
      lost significantly more weight overall (P = 0.028) and regained significantly
      less weight during maintenance and follow-up (P = 0.046) than did the no
      aspartame group. Percentage weight losses at 71 and 175 wk were also positively
      correlated with exercise (r = 0.32, P < 0.001; and r = 0.34, P < 0.01,
      respectively) and self-reported eating control (r = 0.37, P < 0.001; and r =
      0.33, P < 0.01, respectively). These data suggest that participation in a
      multidisciplinary weight-control program that includes aspartame may facilitate
      the long-term maintenance of reduced body weight.

PMID- 9022525
TI  - Differences in macronutrient selections in users and nonusers of an oral
      contraceptive.
AB  - One of the problems inherent in using women in clinical research is the effect
      that oral contraceptive (OC) use might have on physical indexes. Although weight
      gain is frequently reported as a side effect of OC use, there is little empirical
      evidence that such weight gain actually occurs. The current study investigated
      differences in energy balance [ie, dietary intake, resting energy expenditure
      (REE), and physical activity] between groups of users and nonusers of OCs. Each
      group completed a protocol that covered one menstrual cycle and consisted of
      daily recording of dietary intake, measurement of REE once during each phase of
      the menstrual cycle, and reporting of physical activity over the entire cycle.
      Comparisons indicate that there was a marginal interaction (P = 0.06) of OC use
      with total energy intake, indicating a different pattern of intake for the two
      groups. There were qualitative between-group differences such that the OC group
      consumed a greater percentage of energy as fat (P = 0.02) and a lesser percentage
      of energy as carbohydrate (P = 0.008). No group differences were found in the
      percentage of energy consumed as protein, but both groups consumed significantly
      less protein during menses (P = 0.008). There were no significant differences in
      REE. Both groups of women reported marginally more activity (P = 0.09) during
      menses than during the luteal phase.

PMID- 9022526
TI  - Delayed clamping of the umbilical cord improves hematologic status of Guatemalan
      infants at 2 mo of age.
AB  - Iron deficiency anemia is a serious health problem that affects the physical and
      cognitive development of children. Therefore, it is important to develop cost
      effective interventions to improve the hematologic status of the millions of
      children affected by this condition worldwide. We studied 69 Guatemalan infants
      who had been randomly assigned to one of three groups at the time of delivery: 1)
      cord clamping immediately after delivery (n = 21); 2) clamping when the cord
      stopped pulsating, with the infant placed at the level of the placenta (n = 26);
      or 3) clamping when the cord stopped pulsating, with the newborn placed below the
      level of the placenta (n = 22). Maternal and infant hematologic assessments were
      performed at the time of delivery and 2 mo postpartum. At baseline the groups had
      similar socioeconomic, demographic, and biomedical characteristics and the
      newborns had similar hematocrit status. Two months after delivery, infants in the
      two groups with delayed cord clamping had significantly higher hematocrit values
      and hemoglobin concentrations than did those in the early-clamping group. The
      percentage with hematocrit values < 0.33 was 88% in the control group compared
      with 42% in group 2 and 55% in group 3 (P = 0.01). These results suggest that
      waiting until the umbilical cord stops pulsating (approximately 1 min after
      delivery) is a feasible low-cost intervention that can reduce anemia in infants
      in developing countries.

PMID- 9022527
TI  - Body fat estimation in late pregnancy and early postpartum: comparison of two-,
      three-, and four-component models.
AB  - Accurate methods for determining body fat mass during reproduction are necessary
      to evaluate energy balance. However, determination of fat mass is complicated
      during pregnancy by the accretion of water, which invalidates assumptions
      underlying standard two-compartment models. The extent to which the variability
      in body water during pregnancy invalidates use of pregnancy-corrected two
      compartment models for determination of fat mass in individual women is unknown.
      Moreover, it is unclear whether body water returns to nonpregnant values by 2 wk
      postpartum, which is frequently used as the baseline in studies of postpartum
      women. The present study uses a four-component model as a criterion for
      evaluating two- and three-component models. Fifty-six healthy, normotensive women
      between the ages of 19 and 35 y were studied at 36 +/- 1 wk gestation and 15 +/-
      2 d postpartum. Total body water (TBW), total body potassium (TBK), body density,
      and bone mineral content were measured by deuterium dilution, whole-body
      potassium counting, hydrodensitometry, and dual-energy X-ray absorptiometry
      (postpartum only), respectively. At 2 wk postpartum, hydration and density of fat
      free mass (FFM) had not returned to nonpregnant values, and differed between
      lactating and nonlactating women (P < 0.05). Accordingly, standard TBW and body
      density estimates of fat mass differed from four-component estimates at both time
      points (P < 0.005). Moreover, our data indicate that even when pregnancy-specific
      values for hydration or density of FFM are used in TBW and body density models,
      individual fat mass estimates may differ by > 3 kg from the four-component value.
      Fat mass by TBK may differ by > 10 kg from fat mass by the four-component model
      during pregnancy, and by 6 kg postpartum. Use of standard two-compartment models
      to estimate fat mass results in significant error both during pregnancy and at 2
      wk postpartum. Pregnancy-corrected two-compartment models produce reliable mean
      fat mass estimates during pregnancy, but individual fat mass estimates may vary
      widely from four-component values.

PMID- 9022528
TI  - Validation of single daytime samples of human milk to estimate the 24-h
      concentration of lipids in urban Guatemalan mothers.
AB  - The large within- and between-sample variability in breast milk lipid content
      greatly complicates the collection of representative samples in field studies.
      The main purpose of this study was to validate the ability of individual daytime
      samples to predict the 24-h lipid concentration of breast milk. We also studied
      maternal, child, and other factors (time of day and interval between feeds)
      associated with the within- and between-mother variability in milk lipid content.
      Fifty-two primiparous urban Guatemalan women between 1 and 4 mo postpartum were
      studied. Milk samples were collected during six 2-h intervals from 0600 to 1800,
      and throughout the night when the child breast-fed. On average, the 24-h pooled
      milk samples contained 4.2 +/- 0.92% (mean +/- SD) lipids and the best
      concordance with this value was obtained with samples collected between 0600 and
      0800 (concordance correlation coefficient = 0.60, P < 0.05). None of the
      regression equations to predict the 24-h lipid content of breast milk based on
      daytime samples reached a sufficiently high predictive power to be recommended
      for the estimation of individual child intake. Time of day and time elapsed since
      the last feeding were significant determinants of diurnal variations in milk
      lipid content, whereas between-mother variability was explained by maternal
      weight (P = 0.05) and body mass index (P < 0.05). For the collection of milk
      samples in surveys and pre-post studies, we recommend standardization of time of
      day and interval between feeds.

PMID- 9022529
TI  - Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein
      concentrations in hypercholesterolemic men.
AB  - This study examined the effects of garlic and fish-oil supplementation (alone and
      in combination) on fasting serum lipids and lipoproteins in hypercholesterolemic
      subjects. After an initial run-in phase, 50 male subjects with moderate
      hypercholesterolemia were randomly assigned for 12 wk to one of four groups: 1)
      900 mg garlic placebo/d + 12 g oil placebo/d; 2) 900 mg garlic/d + 12 g oil
      placebo/d; 3) 900 mg garlic placebo/d + 12 g fish oil/d, providing 3.6 g n-3
      fatty acids/d; and 4) 900 mg garlic/d + 12 g fish oil/d. In the placebo group,
      mean serum total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and
      triacylglycerols were not significantly changed in relation to baseline. Mean
      group total cholesterol concentrations were significantly lower with garlic+fish
      oil (-12.2%) and with garlic (-11.5%) after 12 wk but not with fish oil alone.
      Mean LDL-C concentrations were reduced with garlic+fish oil (-9.5%) and with
      garlic (-14.2%) but were raised with fish oil (+8.5%). Mean triacylglycerol
      concentrations were reduced with garlic+fish oil (-34.3%) and fish oil alone (
      37.3%). The garlic groups (with and without fish oil) had significantly lower
      ratios of total cholesterol to high-density-lipoprotein cholesterol (HDL-C) and
      LDL-C to HDL-C. In summary, garlic supplementation significantly decreased both
      total cholesterol and LDL-C whereas fish-oil supplementation significantly
      decreased triacylglycerol concentrations and increased LDL-C concentrations in
      hypercholesterolemic men. The combination of garlic and fish oil reversed the
      moderate fish-oil-induced rise in LDL-C. Coadministration of garlic with fish oil
      was well-tolerated and had a beneficial effect on serum lipid and lipoprotein
      concentrations by providing a combined lowering of total cholesterol, LDL-C, and
      triacylglycerol concentrations as well as the ratios of total cholesterol to HDL
      C and LDL-C to HDL-C.

PMID- 9022530
TI  - Desaturation and interconversion of dietary stearic and palmitic acids in human
      plasma and lipoproteins.
AB  - Dietary saturated fatty acids are implicated as a risk factor for
      atherosclerosis. The conversion of the major dietary saturated fatty acids
      stearic acid (18:0) and palmitic acid (16:0) to monounsaturated fatty acids in
      whole plasma and lipoprotein fractions is reported for seven healthy adult humans
      over 6 d using [U-13C]stearic acid (18:0*) and [U-13C]palmitic acid (16:0*) and
      high-precision mass spectrometry. A tracer dose (28-32 mg) of 18:0* or 16:0* was
      loaded into an emulsion and orally administered before breakfast. Serial blood
      samples were collected on day 1 and fasting blood was drawn daily until day 7.
      Overall conversion of 18:0 to 18:1 was approximately 14%, whereas that of 18:0 to
      16:0 was approximately 2% in plasma up to 144 h. Conversion of 16:0 to 16:1 was <
      2%, whereas conversion of 16:0 to 18:0 was approximately 6%. No other fatty acid
      metabolites were detected for 18:0* or 16:0*. The conversion products were
      observed mainly in chylomicrons and very-low-density lipoproteins, indicating
      that the intestine and liver have comparable roles in desaturating 18:0 and 16:0.
      Overall, these data indicate that dietary 18:0 desaturation is severalfold
      greater than 16:0 desaturation. The low level (14%) of 18:0 desaturation in
      omnivorous adults may have little influence on blood lipid profiles relevant to
      atherosclerosis risk.

PMID- 9022531
TI  - n-3 fatty acids and urinary excretion of nitric oxide metabolites in humans.
AB  - Fish oils rich in n-3 fatty acids have been shown to augment endothelium
      dependent vasodilation in human peripheral and coronary arteries. This suggests
      that n-3 fatty acids may enhance arterial nitric oxide production. To explore
      this hypothesis we measured total urinary nitrate output in healthy volunteers
      supplemented with a fish oil concentrate (FOC; n = 15) or purified
      eicosapentaenoic acid (EPA; n = 14) in a placebo-controlled, parallel-group
      study. The FOC contained 41% EPA and 23% docosahexaenoic acid (DHA) ethyl esters,
      whereas EPA was 91% pure; the placebo contained olive oil ethyl esters. Doses
      were 5 g placebo, 5 g FOC, and 3 g EPA to keep the total n-3 fatty acid content
      equal in the latter two groups. The placebo period was 2 wk long and was followed
      by a 3-wk n-3 fatty acid phase. At the end of each period, 24-h urine collections
      and fasting blood samples were obtained. Serum and urinary nitrate concentrations
      were measured in a blinded fashion. The FOC produced a 43% increase in daily,
      creatinine-adjusted, nitrate excretion rates (P < 0.029). Because serum nitrate
      concentrations were not different, these findings suggest that FOC
      supplementation may stimulate systemic nitric oxide synthesis. The lack of effect
      with EPA supplementation suggests that this component of the FOC is not likely to
      be an active component. If confirmed, these observations suggest another
      mechanism whereby n-3 fatty acids may be antiatherogenic.

PMID- 9022532
TI  - Retinal and brain accretion of long-chain polyunsaturated fatty acids in
      developing felines: the effects of corn oil-based maternal diets.
AB  - A study was carried out in domestic felines to determine whether corn oil-based
      maternal diets are an adequate source of essential fatty acids to support normal
      accumulation of long-chain polyunsaturated fatty acids in the brains and retinas
      of offspring and whether these diets have any subsequent effect on visual
      function. Female domestic felines were acclimated to one of six different defined
      diets 1 mo before mating and maintained on the diets throughout pregnancy and
      lactation. Four diets contained only corn and hydrogenated coconut oils as their
      source of fat in ratios of 1:9, 3:7, 6:4, and 9:1, respectively. Two reference
      diets also contained the long-chain polyunsaturated fatty acids arachidonate
      (20:4n-6) and docosahexaenoate (22:6n-3). When the offspring were 8 wk old,
      electroretinograms were obtained and the a- and b-wave implicit times were
      determined. The results showed that animals raised in litters in which the
      maternal diets were devoid of 20:4n-6 and 22:6n-3 had an increase in a- and b
      wave implicit times compared with the controls. In the rod outer segments and
      brains of these animals, there were lower amounts of 22:6n-3 and higher amounts
      of long-chain n-6 polyunsaturated fatty acids compared with control animals.
      These findings showed that although corn oil-based diets were capable of
      maintaining 20:4n-6 concentrations in the developing brain and retina, only those
      diets containing 22:6n-3 could support a high accumulation of docosahexaenoic
      acid in these tissues. Moreover, low amounts of 22:5n-6 in the brains of animals
      in all of the corn oil-diet groups suggested that young felines have a low
      biosynthetic capacity to produce this fatty acid or 22:6n-3. These findings
      suggest that in juvenile felines, maintenance of 22:6n-3 status in the nervous
      system is important for optimal retinal function.

PMID- 9022533
TI  - Continuous 24-h L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine oral-tracer
      studies at an intermediate phenylalanine intake to estimate requirements in
      adults.
AB  - The daily rates of whole-body phenylalanine oxidation (phe-ox) and hydroxylation
      (phe-OH) were determined in young men (n = 10) receiving [13C]phenylalanine and
      [2H2]tyrosine via primed constant oral infusion (four also received
      simultaneously [2H4]tyrosine and [2H3]leucine via primed constant intravenous
      infusions) continuously for 24 h (first 12 h fast and then 12 h fed). The
      subjects were given a diet supplying a proposed requirement phenylalanine intake
      (six subjects: 39 mg phenylalanine.kg-1.d-1 without tyrosine; four subjects: 36
      mg phenylalanine plus 6.8 mg tyrosine), based on an otherwise adequate L-amino
      acid mixture for 6 d before the tracer study. Our hypothesis was that the
      subjects would be in approximate body phenylalanine equilibrium at these intakes.
      Estimates of the daily rate of phe-ox were 26.9 +/- 7.5 mg.kg-1.d-1 (17.2 +/- 5.2
      and 9.7 +/- 3.2 mg.kg-1.d-1 during the 12-h fast and fed periods, respectively),
      and for phe-OH they were 32.1 +/- 11.9 mg.kg-1.d-1 (21.7 +/- 10.5 and 10.4 +/-
      2.5 mg.kg-1.d-1 during the 12-h fast and fed periods, respectively). The daily
      phenylalanine balance was approximately neutral (P > 0.05) when based on phe-ox
      or phe-OH (+4.73 +/- 7.34 and -0.41 +/- 12.6 mg.kg-1.d-1, respectively). In
      comparison with recent, comparable 24-h tracer studies at deficient (22 mg.kg-1.d
      1) and generous (100 mg.kg-1.d-1) phenylalanine intakes, these results support
      the hypothesis that a phenylalanine intake of 39 mg.kg-1.d-1 (without significant
      tyrosine) approximates the mean requirement in healthy adults. This contrasts
      with the upper requirement value of 14 mg.kg-1.d-1 for the total of the aromatic
      amino acids proposed in 1985 by FAO/WHO/UNU.

PMID- 9022534
TI  - Splanchnic and whole-body leucine kinetics in young and elderly men.
AB  - Whole-body and splanchnic protein metabolism were determined in six young (mean
      age: 22.7 y) and six old (68.2 y) men before and during a standardized meal (41.8
      kJ/kg) containing 15.6% protein, by using a combination of intravenous
      ([13C]leucine) and oral ([2H3]leucine) tracers. In the postabsorptive state,
      leucine flux and oxidation were similar in both groups when corrected for lean
      body mass (mean +/- SEM: 1.80 +/- 0.09 compared with 1.79 +/- 0.07 mumol.kg-1.min
      1 and 0.55 +/- 0.02 compared with 0.49 +/- 0.04 mumol.kg-1.min-1 for young and
      old men, respectively, NS). The pattern of response to the meal was also similar
      in young and old men: increased flux and oxidation, decreased protein breakdown,
      and unchanged protein synthesis. Splanchnic extraction of dietary leucine was
      twice as high in elderly men (50 +/- 11% compared with 23 +/- 2%, P < 0.05), was
      inversely related to plasma leucine concentration (r = -0.771, P < 0.01), and was
      positively related to body mass index (r = 0.861, P < 0.001). In conclusion, in
      elderly men there is higher leucine extraction by the gut, liver, or both during
      feeding, which could lead to a lower peripheral availability of dietary leucine.

PMID- 9022535
TI  - Erythrocyte vitamin E and plasma ascorbate concentrations in relation to
      erythrocyte peroxidation in smokers and nonsmokers: dose response to vitamin E
      supplementation.
AB  - Many human degenerative diseases involve free radical processes that nutritional
      antioxidants may ameliorate or prevent, but the optimum intake of such nutrients
      has yet to be established. Requirement will depend in part on the level of
      exposure to exogenous and endogenous reactive oxygen species. Smokers incur a
      sustained degree of oxidant stress from both of these sources, increasing their
      requirements for vitamins E and C. Male smokers (n = 50) from a Scottish
      population with habitually low vitamin E and vitamin C intakes consistently had
      lower plasma ascorbate concentrations (P < 0.02) and greater susceptibility to
      hydrogen peroxide-stimulated erythrocyte peroxidation in vitro (P < 0.001) than
      did nonsmokers (n = 50) from the same population. Erythrocyte vitamin E
      concentrations increased in a dose-dependent manner during 20 wk of
      supplementation with 70, 140, 560, and 1050 mg D-alpha-tocopherol/d. In smokers
      each dose was associated with a significant decrease in susceptibility of
      erythrocytes to peroxidation (P < 0.001). However, red cells of nonsmokers
      receiving the 1050-mg supplement had an increased susceptibility to peroxidation.
      Moreover, prolonged supplementation with D-alpha-tocopherol in nonsmokers induced
      a decline in plasma ascorbate concentration (P < 0.02) in association with an
      increasing erythrocyte vitamin E uptake (P < 0.001), and in nonsmokers receiving
      1050 mg, the susceptibility to peroxidation also increased (P < 0.001). Thus,
      vitamin E may have prooxidant activity in nonsmokers at high and prolonged
      intakes.

PMID- 9022536
TI  - No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on
      oxidative DNA damage estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion
      in smokers.
AB  - The protective effect of fruit and vegetables against cancer has been related to
      their high antioxidant content. However, results from intervention trials have
      not been conclusive on the protective effect of antioxidant supplementation. In a
      randomized placebo-controlled trial we investigated the effect of dietary
      supplementation with antioxidants on a biomarker of oxidative DNA damage with
      mechanistic relation to carcinogenesis. One hundred forty-two smoking men aged 35
      65 y were randomly assigned to one of the following seven treatments for 2 mo:
      100 mg D-alpha-tocopheryl acetate plus 250 mg slow-release ascorbic acid twice a
      day (n = 20), 100 mg D-alpha-tocopheryl acetate twice a day (n = 20), 250 mg
      ascorbic acid twice a day (n = 21), 250 mg slow-release ascorbic acid twice a day
      (n = 21), 30 mg coenzyme Q10 in oil three times a day (n = 20), 30 mg coenzyme
      Q10 as granulate three times a day (n = 20), or placebo twice a day (n = 20). The
      trial outcome was the urinary excretion rate of 8-oxo-7, 8-dihydro-2'
      deoxyguanosine (8-oxodG)-a repair product of oxidative DNA damage. Two months of
      supplementation did not result in significant changes in the urinary excretion
      rate of 8-oxodG in any group. The lack of effect of antioxidant supplementation
      on the excretion rate of 8-oxodG, despite substantial increases in plasma
      antioxidant concentrations, agrees with the results from recent large
      intervention studies with cancer as an endpoint. The cancer-protective effect of
      fruit and vegetables seems to rely not on the effect of single antioxidants but
      rather on other anticarcinogenic compounds or on a concerted action of several
      micronutrients present in these foods.

PMID- 9022537
TI  - Identification of biotin sulfone, bisnorbiotin methyl ketone, and tetranorbiotin
      l-sulfoxide in human urine.
AB  - In previous studies using the HPLC and avidin-binding assay, five unidentified
      avidin-binding substances were observed in human urine. The present study
      investigated the identity of these substances. Urine was collected before and
      after intravenous administration of 18.5 mumol biotin to healthy adults. Unknown
      substances 1 and 3 were initially identified as biotin sulfone and bisnorbiotin
      methyl ketone, respectively, by coelution with authentic standards on HPLC.
      Identities were confirmed by thin-layer chromatography and by derivatization with
      p-dimethyl-aminocinnamaldehyde. As expected for biotin metabolites, the urinary
      excretion of biotin sulfone and bisnorbiotin methyl ketone increased with biotin
      administration. The urinary excretion of biotin sulfone increased 21-fold from
      0.2 nmol/h before to 4.2 nmol/h after administration; the excretion of
      bisnorbiotin methyl ketone increased 130-fold from 0.4 to 51.8 nmol/h. At
      presumed steady state in free-living subjects (n = 6), biotin sulfone and
      bisnorbiotin methyl ketone accounted for 3.6% and 7.9% of total biotin excretion,
      respectively. Traces of tetranorbiotin-l-sulfoxide were also identified by using
      thin-layer chromatography and derivatization with p-dimethylaminocinnamaldehyde.
      However, tetranorbiotin-l-sulfoxide was not detectable in urine by the HPLC and
      avidin-binding assay because this metabolite has weak avidin-binding affinity. We
      conclude that biotin sulfone and bisnorbiotin methyl ketone are present in
      measurable quantities in human urine; their quantitation should allow more
      accurate studies on human biotin metabolism and turnover.

PMID- 9022538
TI  - Ornithine alpha-ketoglutarate metabolism after enteral administration in burn
      patients: bolus compared with continuous infusion.
AB  - Ornithine alpha-ketoglutarate (OKG) has been successfully used as an enteral
      supplement in the treatment of catabolic states, including burn injury. However,
      specific questions remain unanswered concerning burn patients, including OKG
      metabolism and metabolite production, appropriate mode of administration, and
      dose. We thus performed a kinetic study and followed plasma ornithine and OKG
      metabolite concentrations on day 7 postburn in 42 (35 men, 7 women) consecutive
      burn patients aged 33 +/- 2 y with a mean (+/-SEM) total burn surface area (TBSA)
      of 31 +/- 1%. Patients were randomly assigned to receive OKG as a single bolus
      (10 g; n = 13) or in the form of a continuous gastric infusion (10, 20, or 30 g/d
      over 21 h; n = 13) or an isonitrogenous control (n = 16). Plasma pharmacokinetics
      of ornithine followed a one-compartment model with first-order input (r = 0.993,
      P < 0.005). OKG was extensively metabolized in these patients (absorption
      constant = 0.028 min-1, elimination half-life = 89 min), with the production of
      glutamine, arginine, and proline; proline was quantitatively the main metabolite
      [in OKG bolus, area under the curve (AUC)0-7h: proline, 41.4 +/- 5.6 mmol.min/L;
      glutamine, 20.4 +/- 5.7 mmol.min/L; and arginine, 7.3 +/- 1.9 mmol.min/L].
      Proline production was dose-dependent and quantitatively similar between modes of
      OKG administration. Glutamine and arginine production were not dose-dependent and
      were higher in the bolus group than in the infusion group. Overall, the bolus
      mode of OKG administration appeared to be associated with higher metabolite
      production compared with continuous infusion in burn patients, especially for
      glutamine and arginine.

PMID- 9022539
TI  - Separate effects of the coffee diterpenes cafestol and kahweol on serum lipids
      and liver aminotransferases.
AB  - The coffee diterpene cafestol occurs in both robusta and arabica beans. It is
      present in unfiltered coffee brews and raises serum concentrations of
      cholesterol, triacylglycerols, and alanine aminotransferase in humans. The
      effects are linear with the cafestol dose. Unfiltered coffee also contains the
      related compound kahweol, which occurs only in the major coffee strain arabica.
      The activity of kahweol is unknown. In a randomized, double-blind crossover
      study, we gave 10 healthy male volunteers either pure cafestol (61-64 mg/d) or a
      mixture of cafestol (60 mg/d) and kahweol (48-54 mg/d) for 28 d. Relative to
      baseline values, cafestol raised mean (+/-SEM) total serum cholesterol
      concentrations by 0.79 +/- 0.14 mmol/L (31 +/- 5 mg/dL), low-density-lipoprotein
      (LDL) cholesterol by 0.57 +/- 0.13 mmol/L (22 +/- 5 mg/dL), fasting triacy
      glycerols by 0.65 +/- 0.12 mmol/L (58 +/- 11 mg/dL), and alanine aminotransferase
      by 18 +/- 2 U/L (all P < 0.01). Relative to cafestol alone, the mixture of
      cafestol plus kahweol increased total cholesterol by another 0.23 +/- 0.16 mmol/L
      (9 +/- 6 mg/dL) (P = 0.08), LDL cholesterol by 0.23 +/- 0.16 mmol/L (9 +/- 6
      mg/dL) (P = 0.09), triacylglycerols by 0.09 +/- 0.10 mmol/L (8 +/- 9 mg/dL) (P =
      0.20), and alanine aminotransferase by 35 +/- 11 U/L (P = 0.004). Thus, the
      effect of cafestol on serum lipid concentrations was much larger than the
      additional effect of kahweol, and the hyperlipidemic potential of unfiltered
      coffee mainly depends on its cafestol content. Both cafestol and kahweol raised
      alanine aminotransferase concentrations, and their hyperlipidemic effect thus
      seems not to be coupled with their effect on liver cells.

PMID- 9022540
TI  - Acute effects of exercise on postprandial lipemia: a comparative study in trained
      and untrained middle-aged women.
AB  - Repeated episodes of exaggerated postprandial lipemia may hasten the progression
      of atherosclerosis. The purpose of this study was to compare the lipemic response
      to a high-fat meal in trained and untrained women in the presence and absence of
      the acute effects of exercise. Nine endurance-trained and thirteen untrained
      women aged 40.4 +/- 3.3 and 43.8 +/- 4.3 y (mean +/- SD), with maximal oxygen
      uptake of 50.3 +/- 5.9 and 31.7 +/- 3.6 mL.kg-1.min-1, and a body mass index
      (kg/m2) of 22.2 +/- 0.9 and 22.9 +/- 2.3, respectively, underwent two trials,
      each over 2 d. Subjects did not exercise during the 2 d leading up to a trial. On
      day 1 they either walked for 90 min at 60% of maximal oxygen uptake (exercise),
      or refrained from exercise (control). On day 2 venous blood and expired air
      samples were obtained in the fasted state and for 6 h after consumption of a high
      fat meal (1.70 g fat, 1.65 g carbohydrate, and 0.25 g protein/kg fat-free mass).
      Exercise decreased lipemia as determined by the mean (+/-SEM) area under the
      plasma triacylglycerol concentration versus time curve: trained, 6.96 +/- 0.48
      compared with 4.87 +/- 0.33 mmol.h/L; untrained, 8.36 +/- 0.83 compared with 7.01
      +/- 0.79 mmol.h/L (control and exercise trials, respectively, both P < 0.05).
      Lipemia differed significantly between groups in the presence of this acute
      effect of exercise but not in its absence. Exercise decreased insulinemia in
      trained women (543 +/- 25 compared with 433 +/- 24 pmol.h/L, P < 0.01) but had no
      effect in untrained women (592 +/- 34 compared with 585 +/- 47 pmol.h/L). Total
      oxidation of fat over the 6-h postprandial period was enhanced by exercise, and
      to a similar degree in each group of women.

PMID- 9022541
TI  - Orthotopic liver transplantation reverses the adverse nutritional changes of end
      stage liver disease in children.
AB  - The changes in growth and body composition after orthotopic liver transplantation
      (OLT) were studied in 61 children [median age at OLT 3.49 y (range: 0.04-14.5 y),
      26 boys and 35 girls] who had survived > or = 1 y post-OLT. Height, weight,
      midarm circumference (MAC), triceps skinfold thickness (TSF), and subscapular
      skinfold thickness (SSF) were measured at OLT, 3 and 6 mo later, then annually up
      to 5 y. SD scores (SDS) were derived from population standards. Results are
      reported as mean SDS +/- SEM. At OLT the children were short and malnourished
      (height: -0.98 +/- 0.22; weight -0.82 +/- 0.18; MAC: -1.77 +/- 0.21; TSF: -1.27
      +/- 0.17; SSF: -1.49 +/- 0.17). By 3 mo post-OLT, there was a sustained
      improvement in MAC (-0.73 +/- 0.22), TSF (-0.48 +/- 0.18), and SSF (-0.50 +/-
      0.18). Weight SDS (-0.48 +/- 0.20) improved by 6 mo without significant change in
      height SDS. The three children with Alagille syndrome were smaller (height,
      weight, and MAC) than children with other diagnoses but did show catch-up growth.
      Fulminant hepatic failure was not associated with growth failure before or after
      OLT. Infants (n = 14) were smaller and more malnourished at OLT (smaller skinfold
      thicknesses and lower weight SDS) than those who received transplants at an older
      age. By 1 y post-OLT, the only persisting difference was in TSF. Abnormal liver
      function at 1 y post-OLT (n = 8) and repeated episodes of steroid-treated
      rejection (n = 13) were associated with worsening height and weight SDS. The use
      of tacrolimus for graft salvage from rejection (n = 6) was not associated with
      growth failure. In conclusion, end-stage liver disease has a more adverse effect
      on MAC, TSF, and SSF than on height and weight, but a marked and rapid
      improvement occurred post-OLT. Children who were most severely malnourished and
      growth restricted at the time of OLT showed the greatest catch-up growth after
      OLT.

PMID- 9022542
TI  - Apolipoprotein E phenotype and diet-induced alteration in blood pressure.
AB  - The purpose of the study was to answer the following two questions. First, are
      the diet-induced changes in the plasma cholesterol concentration associated with
      a change in blood pressure? Second, is the possible diet-induced change in blood
      pressure related to the apolipoprotein E (apo E) phenotype? Two hundred employees
      of our hospital volunteered and among those, 23 subjects with the apo E3 (E3,3)
      and 21 with the apo E4 phenotype (E4,3 or 4,4) were selected. The apo E groups
      were age- and sex-matched. Study subjects were healthy, had normal body weights,
      and their mean (+/-SD) age was 37.9 +/- 7.7 y. The total energy derived from
      dietary fat was 37%, 26%, and 38% during the baseline, low-fat, and high-fat diet
      periods, respectively. The two intervention diets were consumed by the study
      subjects for 4 wk at a time. During the trial blood pressure was measured once a
      week with an automatic device under standardized conditions. Systolic, diastolic,
      and mean arterial pressures were significantly reduced during the low-fat diet
      period compared with baseline, but not compared with the high-fat diet period
      among the apo E4 subjects only (-6%, -4.5%, and -6%, respectively). The high-fat
      diet was associated with elevation of blood pressure among 70% of study subjects.
      A slight but significant positive correlation was noted between the plasma total
      cholesterol concentration and blood pressure, more so among the apo E4 subjects.
      Furthermore, age was correlated with blood pressure response in apo E4 subjects.
      In conclusion, both the systolic and diastolic blood pressures were significantly
      altered during the different diet periods. The dietary response of blood pressure
      seemed to differ between subjects with the apo E4 and those with the apo E3
      phenotype.

PMID- 9022543
TI  - Relation of plasma phospholipid and cholesterol ester fatty acid composition to
      carotid artery intima-media thickness: the Atherosclerosis Risk in Communities
      (ARIC) Study.
AB  - We examined the relation of fatty acid composition of plasma phospholipids and
      cholesterol esters with carotid artery intima-media thickness (a measure of
      atherosclerosis) in 2872 white men and women aged 45-64 y from the Minneapolis
      center of the Atherosclerosis Risk in Communities Study. In both men and women,
      average carotid intima-media thickness was associated significantly (P < 0.01)
      and positively with saturated (SFA) and monounsaturated fatty acid composition,
      and inversely with polyunsaturated fatty acid (PUFA) composition and the ratio of
      PUFAs to SFAs in both phospholipids and cholesterol esters. These associations
      were independent of age, cigarette smoking, low-density-lipoprotein (LDL)
      cholesterol, high-density-lipoprotein (HDL) cholesterol, body mass index,
      diabetes, and hypertension in men; but in women, only SFAs and PUFAs in the
      cholesterol esters and the ratio of PUFAs to SFAs were independently associated.
      The plasma fatty acid pattern is associated with carotid atherosclerosis in a
      direction generally consistent with the dietary fat-coronary artery disease
      relation. These results support recommendations to reduce dietary saturated fat
      to prevent cardiovascular disease.

PMID- 9022544
TI  - Efficacy of multiple dietary therapies in reducing cardiovascular disease risk
      factors.

PMID- 9022545
TI  - Cigarette smoking and antioxidant vitamins: the smoke screen continues to clear
      but has a way to go.

PMID- 9022546
TI  - Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory
      bowel disease.
AB  - The ability of inflammatory bowel disease (IBD) patients to tolerate dairy
      products and the guidance they receive from physicians and nutritionists on this
      subject are important considerations in the management of their IBD. Although
      most affected persons are able to consume a glass of milk daily without
      discomfort, additional consideration must be given to specific factors that can
      be relevant to certain individuals. The declaration by patients that they are
      "dairy sensitive" may be related to lactose intolerance or malabsorption, the
      long-chain triacylglycerol content of milk, allergy to milk proteins, as well as
      psychologic factors and the misconception that dairy products can be detrimental
      to their health. The prevalence of lactose malabsorption is significantly greater
      in patients with Crohn disease involving the small bowel than it is in patients
      with Crohn disease involving the colon or ulcerative colitis. In the latter
      colonic conditions the prevalence of lactose malabsorption is mainly determined
      by ethnic risk, which is based on genetic factors. In addition, lactose
      malabsorption in Crohn disease of the small bowel may be determined by factors
      other than lactase enzyme activity, such as bacterial overgrowth and/or small
      bowel transit time. Physicians differ widely in the advice they give their
      patients: some dogmatically advise avoidance of dairy products when the diagnosis
      is made whereas others discount the possible role of dairy in the management of
      IBD. IBD patients avoid dairy products more than they would need to based on the
      prevalence of lactose malabsorption and/or milk intolerance, probably partly
      because of incorrect patient perceptions and arbitrary advice from physicians and
      authors of popular diet books. Adequate scientific and clinical information is
      now available to permit recommendations about the intake of dairy products for
      each IBD patient.

PMID- 9022547
TI  - Nutrition coverage on medical licensing examinations in the United States.
AB  - The 1985 National Academy of Sciences report Nutrition Education in US Medical
      Schools recommended that the National Board of Medical Examiners (NBME), who
      develops the US Medical Licensing Examination (USMLE), cover basic nutrition
      knowledge. According to the NBME, the USMLE includes nutrition on their Step 1
      and 2 exams; however, this coverage has been questioned. To document whether the
      NBME adequately addresses nutrition, the 1986 Part I and Part II and the 1993
      Step 1 and step 2 exams, which replaced the Part I and II exams, were reviewed by
      five nutrition professionals. This review identified the nutrition-related areas
      of the two-part exams and how the extent of nutrition coverage changed from 1986
      to 1993. Nutrition items were coded on four dimensions: 1) specific nutrition
      related topic area, 2) normal or abnormal scenario, 3) related organ system, and
      4) importance in clinical medicine. The percentage of nutrition-related items, as
      identified by the nutrition professionals, increased from 9% on the 1986 Part I
      exam to 11% on the 1993 Step 1 exam and from 6% on the 1986 Part II exam to 12%
      on the 1993 Step 2 exam. The percentage of nutrition items related to vitamin
      deficiencies increased from 1986 to 1993 on both halves of the exam. Nutrition
      coverage on the USMLE Step 1 and Step 2 seems adequate in amount, however, the
      content and appropriateness of the items were not evaluated. The observed
      increased focus on vitamin deficiencies should be further considered.

PMID- 9022548
TI  - Call for endorsement of a petition to the Food and Drug Administration to always
      add vitamin B-12 to any folate fortification or supplement.

PMID- 9022549
TI  - Relation between choline and carnitine homeostasis.

PMID- 9022550
TI  - beta-Carotene, malondialdehyde, and cystic fibrosis.

PMID- 9022551
TI  - Vitamins may have different effects at different intakes.

PMID- 9022552
TI  - Weighing the evidence: the Canadian experience.
AB  - The Canadian Task Force on the Periodic Health Examination created a hierarchy of
      evidence that has been used for the past 18 y to evaluate the scientific evidence
      for and against the preventability of each condition reviewed. The methodology
      developed by the task force may be applicable to study of the preventive aspects
      of dietary sodium and health. This paper describes the history and modus operandi
      of the task force.

PMID- 9022553
TI  - Genetic and nongenetic determinants of salt sensitivity and blood pressure.
AB  - Salt sensitivity is characterized by an alteration of kidney function that
      necessitates higher arterial pressure to excrete a given amount of sodium and is
      expressed as a reduction in the slope of the pressure-natriuresis relation.
      Excess renal exposure to catecholamines, angiotensin II, aldosterone, and other
      mineralocorticoids all reduce the sensitivity of the pressure-natriuretic
      relation and lead to salt sensitivity. Inhibition of these pathways has opposite
      effects, as do excess circulating atrial natriuretic peptide and overactivity of
      various intrarenal paracrine systems, including vasodilator and natriuretic
      products of arachidonic acid metabolism, such as prostaglandin E2 and kinins.
      Salt sensitivity can also be inherited and ongoing studies are attempting to
      identify the genes that contribute to this trait. Abnormalities of renal function
      of Dahl salt-sensitive rats appear to precede the hypertension resulting from
      high salt intake. Although polymorphic differences have been identified between
      the Dahl salt-sensitive rat and normotensive rats, the specific genes
      contributing to the salt sensitivity have not yet been determined.

PMID- 9022554
TI  - Overview of dietary sodium effects on and interactions with cardiovascular and
      neuroendocrine functions.
AB  - The battle over salt has changed over the centuries from one of where to find
      salt sources to one of how much salt to use in a healthful manner. Many questions
      were answered by the INTERSALT Study across numerous countries and, yet, many
      questions persist. It is a love-hate relationship, an approach-avoidance
      paradigm. We need it but in excess it may cause harm. Questions that still remain
      are, Who is salt sensitive? What are the most appropriate and relevant models to
      study? What are the functional differences of the many salt effects? Can the data
      support a single public policy on dietary sodium recommendations? The following
      review examines some of these questions and the interaction of neural,
      neuroendocrine, renal, and social factors in the great salt debate. Dietary
      sodium can alter peripheral and central neurotransmitter concentrations, receptor
      density, and sensitivity. Low-sodium diets can produce acute neuroendocrine and
      neural compensations that are different from the chronic effects of low dietary
      sodium. Chronic high- or low-sodium diets may also cause trophic hormonal changes
      that can influence resistance vessel structure and, consequently, blood pressure.
      Both human and animal studies suggest a genetic basis for salt sensitivity. In
      some cases stress unmasks the salt sensitivity. For instance, the social context
      can modulate blood pressure responses to a high-sodium diet. Therefore, 24-h
      monitoring of blood pressure becomes important, especially in salt-sensitive
      persons.

PMID- 9022555
TI  - Dietary sodium chloride and potassium have effects on the pathophysiology of
      hypertension in humans and animals.
AB  - A diet high in NaCl can raise blood pressure in susceptible people and animals,
      probably by similar mechanisms. The possibly harmful effects of a high-NaCl diet
      are not unexpected because both prehistoric humans and mammals evolved in a low
      NaCl environment. Evolutionary forces molded mammals to adapt well to a low
      sodium intake; modern high NaCl intakes go against this adaptation. A high-NaCl
      diet can cause premature mortality by raising blood pressure in susceptible
      people. We have new evidence that in hypertension, a high-NaCl diet can cause a
      great increase in mortality even though it does not cause a further blood
      pressure rise, partially because of multiple small cerebral infarcts. Recent
      evidence also indicates that a high-potassium diet reduces the rise of blood
      pressure caused by a high-NaCl diet, whereas a low-normal potassium intake
      encourages an NaCl-induced blood pressure rise. The combination of a tendency by
      the kidneys to retain NaCl together with a high NaCl intake can produce a blood
      pressure rise. This combination tends to cause NaCl retention, which can trigger
      blood pressure rises in susceptible humans and animals. Such blood pressure rises
      can augment renal NaCl excretion and regain the previous NaCl balance. In Dahl
      salt-sensitive rats several renal abnormalities encourage sodium retention. By
      analogy, renal "abnormalities" are probably present in people susceptible to
      hypertension.

PMID- 9022556
TI  - Heterogeneous responses to changes in dietary salt intake: the salt-sensitivity
      paradigm.
AB  - Blood pressure responses to increases and decreases in dietary salt intake are
      heterogeneous. In some hypertensive individuals, decreases in blood pressure with
      salt restriction are clinically significant and approach that achieved with
      medication. In others, little or no change in blood pressure occurs, whereas in
      still others, blood pressure may actually increase with salt restriction. The
      heterogeneous responses are partly acquired and involve the influences of age,
      the intake of other electrolytes, and the influence of certain medications.
      Genetic predisposition may also play a substantial role because salt sensitivity
      is increased in black individuals and in persons with non-insulin-dependent
      diabetes mellitus. Some uncommon but readily diagnosed salt-sensitive genetic
      syndromes, such as glucocorticoid-remediable aldosteronism and Liddle syndrome,
      have been identified. Short-term volume expansion and contraction and longer-term
      dietary interventions appear to be reproducible and may be used to identify salt
      sensitive and salt-resistant individuals; however, these maneuvers are cumbersome
      and cannot be used on a large scale. Molecular genetic techniques for identifying
      individuals with salt-sensitive and salt-resistant essential hypertension are not
      yet available, but if the putative gene polymorphisms are identified, such
      techniques may replace the current trial-and-error methods.

PMID- 9022557
TI  - Blood pressure response to sodium in children and adolescents.
AB  - The predisposition to primary hypertension is composed of genetic factors, and
      aberrant mechanisms leading to the clinical expression of hypertension may be
      operational in children and adolescents. Dietary composition may play a role in
      the expression of hypertension. The effects of diet on blood pressure in the
      young may be indirect, reflecting the relation of diet with growth and body
      composition. Alternatively, there may be a direct effect of a specific dietary
      factor, such as sodium, on mechanisms regulating blood pressure. The average
      daily sodium intake by children and adolescents exceeds recommended amounts.
      Despite the high sodium intake among children, there are few data showing that
      decreasing sodium intake lowers blood pressure. Children who do express blood
      pressure sensitivity to sodium intake also have related risk factors for
      cardiovascular disease such as a positive family history or obesity. Prospective
      data are needed in children with characteristic risk factors to determine whether
      sodium intake contributes to the pathogenesis of hypertension and whether this
      course can be modified by alterations in diet.

PMID- 9022558
TI  - Nature and role of observational studies in public health policy concerning the
      effects of dietary salt intake on blood pressure.
AB  - Does dietary sodium in excess of a specified daily consumption substantively
      elevate blood pressure in normotensive people? Does lowering the daily
      consumption of sodium reduce blood pressure in normotensive people? Sound
      observational and interventional studies can address these questions, but there
      are substantial differences in the ability of various research designs to provide
      clear, bias-free answers. I summarize established scientific principles for
      addressing issues of causation and the effects of interventions and compare
      observational and interventional designs. Observational studies are important in
      exploring the possible determinants of health problems but are subject to bias
      and cannot directly assess the effects of interventions. They are superseded by
      sound interventional studies, particularly randomized controlled trials, in
      answering the key questions concerning causes and benefits of intervention.

PMID- 9022559
TI  - The INTERSALT Study: background, methods, findings, and implications.
AB  - The INTERSALT Study is a standardized, worldwide epidemiologic study of large
      sample size (n = 10079 men and women aged 20-59 y from 32 countries) that tested
      both within- and cross-population prior hypotheses on 24-h sodium excretion and
      blood pressure. For individuals, a significant, positive, independent linear
      relation between 24-h sodium excretion and systolic blood pressure (SBP) was
      found. With multivariate adjustment for underestimation, the estimated effect of
      a sodium intake higher by 100 mmol/d was higher SBP/DBP (diastolic blood
      pressure) by approximately 3-6/0-3 mm Hg. This relation prevailed for both men
      and women, for younger and older people, and for 8344 people without
      hypertension. In tests of prior cross-population hypotheses (n = 52),
      significant, independent relations were found between sample 24-h median urinary
      sodium excretion and sample median SBP and DBP, prevalence rate of hypertension,
      and slope of SBP and DBP from age 20 to 59 y (median sodium intake greater by 100
      mmol/d was associated with a 30-y increase in SBP/DBP, i.e., at the age of 55 y
      compared with 25 y, of 10-11/6 mm Hg. The INTERSALT results, which agree with
      findings from other diverse studies, including data from clinical observations,
      therapeutic interventions, randomized controlled trials, animal experiments,
      physiologic investigations, evolutionary biology research, anthropologic
      research, and epidemiologic studies, support the judgment that habitual high salt
      intake is one of the quantitatively important, preventable mass exposures causing
      the unfavorable population-wide blood pressure pattern that is a major risk
      factor for epidemic cardiovascular disease.

PMID- 9022560
TI  - Randomized trials of sodium reduction: an overview.
AB  - We updated a previously published overview of randomized clinical trials testing
      the effects of reducing sodium intake. We excluded trials that had confounded
      designs, enrolled preadolescent study populations, tested intakes outside the
      usual range for the US population, or reported neither systolic nor diastolic
      blood pressure. Thirty-two trials with outcome data for 2635 subjects were
      included. Two reviewers abstracted information independently and differences were
      reconciled. Pooled blood pressure differences between treated and control groups
      were highly significant for all trials combined and for trials in hypertensive
      and normotensive subjects pooled separately. The effects on blood pressure of
      lowering sodium in hypertensive and normotensive subjects, respectively (each
      trial weighted according to sample size), were -4.8/-2.5 and -1.9/-1.1 mm Hg
      (systolic/diastolic). Median differences in sodium excretion between sodium
      reduction and control groups in these subgroups were -77 and -76 mmol/24 h,
      respectively. Weighted linear-regression analyses across the trials showed dose
      responses, which were more consistent for trials in normotensive subjects. These
      associations were, per 100 mmol Na/24 h, -5.8/-2.5 and -2.3/-1.4 mm Hg in
      hypertensive and normotensive subjects, respectively. There is no evidence that
      sodium reduction as achieved in these trials presents any safety hazards. The
      blood pressure reduction that would result from a substantial lowering of dietary
      sodium in the US population could reduce cardiovascular morbidity and mortality.

PMID- 9022561
TI  - Efficacy of nonpharmacologic interventions in adults with high-normal blood
      pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials
      of Hypertension Prevention Collaborative Research Group.
AB  - Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults,
      aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the
      feasibility and blood pressure-lowering effects of seven nonpharmacologic
      interventions (weight loss, sodium reduction, stress management, and
      supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18
      mo, weight loss and sodium reduction were well-tolerated and produced significant
      declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg
      for weight loss and sodium reduction, respectively, at 18 mo). None of the other
      interventions lowered blood pressure significantly at either the 6- or 18-mo
      follow-up visits. These results suggest that both weight loss and sodium
      reduction provide an effective means to prevent hypertension. The long-term
      effects of both of these interventions are being tested in phase 2 of the trial.

PMID- 9022562
TI  - Salt and blood pressure in community-based intervention trials.
AB  - This article reviews community-based salt intervention trials. In the Belgian
      Salt Intervention Trial, a controlled 5-y intervention in two Belgian towns
      resulted in a reduction in urinary sodium of 17 mmol/24 h (P < 0.001) in adult
      (aged > or = 20 y) women in the intervention town, which differed from the
      concurrent trend (an increase of 8 mmol/24 h) in the control town (P = 0.01).
      However, both systolic (-7.5 compared with -7.9 mm Hg) and diastolic (-2.3
      compared with -3.0 mm Hg) pressures declined to the same extent in women of the
      two towns. In adult men in the intervention town, decreases were observed in
      urinary sodium (-12 mmol/24 h) and in systolic (-5.6 mm Hg) and diastolic (-2.4
      mm Hg) blood pressures, but these trends were the same in the control town (-12
      mmol/24 h, -4.9 mm Hg, and 0.2 mm Hg, respectively). The Belgian study and the
      four other community-based salt intervention trials reviewed show that, in
      general, salt intake in the long-run cannot be restricted below 5 g/24 h. More
      moderate salt restriction may constitute a more realistic goal, but its influence
      on blood pressure in the community at large is probably trivial.

PMID- 9022563
TI  - Adverse effects of short-term, very-low-salt diets in subjects with risk-factor
      clustering.
AB  - Obesity is associated with risk-factor clustering, including risk factors for
      hypertension, hyperinsulinemia, resistance to insulin's lowering of glucose and
      fatty acid concentrations, and a complex dyslipidemia. Obese hypertensive
      subjects are presumed to be salt sensitive because of the antinatriuretic actions
      of insulin. However, in our studies obese hypertensive subjects aged < 45 y were
      not more salt sensitive than were lean individuals. Subjects with the greatest
      evidence for risk-factor clustering had higher renin and aldosterone
      concentrations, which increased with salt restriction. The greater rise of fatty
      acids and activation of the renin-angiotensin system may explain the larger
      elevations of blood pressure, insulin, and triacylglycerol with salt restriction
      in high-risk subjects than in low-risk subjects. Regardless of mechanism, the
      adverse effects of short-term, very-low-salt diets in high-risk subjects suggest
      that continued moderation in advice for universal salt restriction is
      appropriate.

PMID- 9022564
TI  - Drug interactions and consequences of sodium restriction.
AB  - Dietary sodium restriction has several clinical benefits, particularly that of
      enhancing the antihypertensive action of diuretics and other blood pressure
      lowering drugs. In individuals who form hypercalciuric stones, sodium restriction
      along with thiazide diuretics helps to reduce urinary calcium. However, there are
      adverse consequences of sodium restriction, particularly in elderly patients with
      impaired sodium conservation mechanisms. Ischemic and nephrotoxic injuries are
      induced more readily in sodium-depleted animals and patients because of impaired
      renal hemodynamics and activation of the renin-angiotensin system. Acute renal
      failure can be precipitated by sodium restriction and concomitant angiotensin
      converting enzyme inhibitors, nonsteroidal antiinflammatory drugs, and
      immunosuppressive drugs. Dietary sodium restriction in animals enhances the
      chronic nephrotoxicity of cyclosporine and tacrolimus, whereas similar doses of
      these drugs do not produce structural damage in salt-replete animals. Maneuvers
      that block angiotensin II protect against renal scarring and drug-induced
      arteriolopathy in this model. Sodium restriction can enhance the renal tubular
      reabsorption of drugs such as lithium, leading to toxic blood concentrations.
      Calcium antagonists may have better efficacy when prescribed to salt-replete
      hypertensive persons. Finally, there is evidence that activation of the renin
      angiotensin system by sodium depletion will enhance the growth of cysts in animal
      models of cystic renal disease. In individual patients, the effects of sodium
      restriction by diet should balance anticipated benefits against any possible
      adverse consequences.

PMID- 9022565
TI  - Urinary sodium excretion and myocardial infarction in hypertensive patients: a
      prospective cohort study.
AB  - Reduced-sodium diets are frequently recommended for hypertensive patients. To
      determine the relation of sodium intake to subsequent cardiovascular disease, 24
      h urinary excretion of sodium, potassium, and creatinine and plasma renin
      activity (PRA) were measured in 2937 mildly and moderately hypertensive patients
      unmedicated for > or = 3-4 wk. Morbidity and mortality in these treated subjects
      were ascertained. Subjects were stratified by sex-specific quartiles of urinary
      sodium excretion; race, cardiovascular status, and blood pressure before and
      during treatment were similar for each stratum. Patients with lower urinary
      sodium excretion were thinner, excreted less potassium, and had higher PRA.
      During an average 3.8-y follow-up, 55 myocardial infarctions (MIs) occurred.
      Incidence of MIs and urinary sodium excretion were inversely associated in the
      total population and in males but not in females. In males, age- and race
      adjusted MI incidence in the lowest compared with the highest quartile of urinary
      sodium excretion was 11.5 compared with 2.5 (RR: 4.3; 95% CI: 1.7, 10.6). No
      association was observed between mortality from causes other than cardiovascular
      disease (n = 11) and urinary sodium excretion. There was a significant linear
      trend in proportions of MI by quartile of urinary sodium excretion, with a
      breakpoint after the lowest quartile. In Cox multivariate analysis, the logarithm
      of PRA, age, systolic blood pressure, and cholesterol as continuous variables, as
      well as left ventricular hypertrophy and smoking, had a direct association and
      urinary sodium excretion an inverse, independent association (P = 0.036) with
      incidence of MI.

PMID- 9022566
TI  - Effect of dietary sodium restriction on overall nutrient intake.
AB  - Sodium restriction, widely prescribed for hypertensive persons and recommended
      for the broader US population, may result in nutrient alterations that could
      either beneficially or detrimentally affect overall diet quality. Most dietary
      sodium comes from meats (including poultry and fish), grains, and dairy products.
      These three groups also provide most dietary calcium, iron, magnesium, and
      vitamin B-6. Thus, reduced consumption of foods that are primary sodium sources
      could concurrently reduce the dietary content of these other nutrients below
      recommended daily intakes. This consequence of sodium restriction has not been
      specifically addressed in clinical trials. Although intake of most food groups
      was significantly reduced by a sodium-restricted diet in the Hypertension
      Prevention Trial, three other large clinical trials reported differing effects of
      sodium restriction on simultaneous energy and nutrient intakes. In the largest
      study of the effects of a sodium-restricted diet on intake of all major
      nutrients, sodium reduction was accompanied by lower energy intake and,
      concomitantly, lower intakes of total fat, saturated fat, protein, carbohydrate,
      and calcium. Present data are inadequate for determining the potential nutrient
      alterations of a broad prescription of sodium restriction. Difficulties in
      interpreting the available data result from the combination of sodium restriction
      with other interventions, intensive sodium reduction measures that do not reflect
      clinical implementation, poor compliance with sodium restriction, lack of
      analysis of changes in patterns of food intake, and interventions that are too
      short to reflect stable dietary patterns.

PMID- 9022567
TI  - The taste for salt in humans.
AB  - Accumulating evidence indicates that the taste of salt is innately appealing to
      humans, although responses to salty foods are strongly influenced by
      environmental factors. Except in instances of severe, prolonged sodium depletion,
      a sodium-specific appetite has not been documented in humans. Limited data reveal
      no clear association between early exposure to salt and various hedonic responses
      to salt later in life, but recent exposure markedly alters a person's preferred
      salt content of foods. Restricting exposure for 8-12 wk can enhance the appeal of
      reduced-sodium foods in both normotensive and hypertensive individuals. Although
      the appeal of the taste of salt is one factor contributing to its intake, the
      extent to which such a hedonic shift promotes long-term adherence to a reduced
      sodium diet has not been determined. There is little evidence supporting a
      relation between either taste sensitivity or hedonic responses to salt and blood
      pressure.

PMID- 9022568
TI  - Compliance to a low-salt diet.
AB  - Community intervention projects, efforts at single centers, and multicenter,
      prospective, dietary salt-restriction trials suggest that such an intervention is
      neither easy to achieve nor simple to maintain. Community-wide interventions
      based on advertisements, pamphlets, posters, radio messages, instructions in
      schools or other institutions, and cooperation from food suppliers such as
      butchers and bakers resulted in a slight decrease in salt consumption, mostly in
      normotensive women. A demonstration project at a single center showed that
      lowering salt intake long-term by 50% in hypertensive patients was feasible. That
      study included self-administered, positive-feedback devices to indicate adherence
      and a role for a household partner in achieving compliance. Multicenter
      intervention trials also indicate that reducing salt intake in the long term is
      feasible. However, in all intervention trials the subjects were highly selected,
      stable, generally married male volunteers. An elaborate training program
      involving many health care professionals was necessary and recidivism was common.
      Successful intervention requires specific goals and delegated responsibilities on
      the part of the health care team, careful assessment of the patient and the risk
      factors, as well as motivation for behavioral change, a specific plan for
      implementation, repetitive educational efforts, and a built-in monitoring
      mechanism.

PMID- 9022569
TI  - Sodium intake trends and food choices.
AB  - Since 1980 General Mills Inc has regularly conducted studies of the mean daily
      intake of 25 nutrients from nationally representative samples of 4000 American
      households (approximately 10,000 individuals). This paper examines trends in
      sodium consumption derived from these studies. Calculated estimates of both
      discretionary and nondiscretionary intake indicate that overall sodium
      consumption has declined since the early 1980s. Shifts in food sources of sodium
      have occurred over the 10-y study period, with the greatest amounts of sodium
      coming from meats and mixed dishes. Greater interest in the sodium content of the
      diet is predicted because of the daily value listing on the new food label and
      the National Heart, Lung and Blood Institute's campaign to reduce sodium intake.
      Until an acceptable alternative for the salty taste from sodium chloride is
      available, offering reduced-sodium alternatives and gradually reducing the sodium
      content of existing products appears to be the food industry's best approach to
      meet consumers' concerns about sodium.

PMID- 9022570
TI  - Dietary sodium and blood pressure: interactions with other nutrients.
AB  - This paper reviews the evidence that salt sensitivity of blood pressure is
      related both to the anion ingested with sodium as well as to other components of
      the diet. In several experimental models of salt-sensitive hypertension and in
      humans, blood pressure is not increased by a high sodium intake provided with
      anions other than chloride. Salt-induced increase of blood pressure depends on
      the concomitant ingestion of both sodium and chloride. Both epidemiologic and
      clinical evidence suggest that sodium chloride-induced increases of blood
      pressure are augmented by diets deficient in potassium or calcium. In
      experimental animals, a high intake of simple carbohydrates also augments sodium
      chloride sensitivity of blood pressure. These observations indicate that the
      effect of dietary sodium on blood pressure is modulated by other components of
      the diet.

PMID- 9022572
TI  - The role of ultrasound in deep venous thrombosis.

PMID- 9022571
TI  - Role of adequate dietary calcium intake in the prevention and management of salt
      sensitive hypertension.
AB  - During the past decade, a credible body of evidence has emerged supporting the
      concept that maintaining an adequate dietary mineral intake, specifically of
      calcium, magnesium, and potassium, protects against high blood pressure in
      humans. Observational and interventional studies in humans and extensive use of
      laboratory models showed that a significant portion of blood pressure variability
      in response to sodium chloride can be linked to the adequacy of the mineral
      content of the diet. This review summarizes the observational data from several
      large databases showing that when adults meet or exceed the recommended dietary
      allowances of calcium, potassium, and magnesium, the simultaneous ingestion of a
      diet high in sodium chloride is not associated with elevated arterial pressure.
      In fact, a higher sodium chloride intake in these adults is most likely
      associated with the lowest blood pressure in the society. This interaction
      between adequacy of mineral intake and protection against salt sensitivity in
      humans provides an important opportunity for further improving blood pressure
      control in our society. Educating individuals to maintain, on a daily basis,
      adequate intakes of calcium, potassium, and magnesium rather than limit their
      sodium chloride is a viable health recommendation that individuals can implement
      to reduce their risk of sodium chloride-induced hypertension.

PMID- 9022573
TI  - Teaching radiology on the internet.

PMID- 9022574
TI  - Pictorial review: imaging of peripheral nerve tumours.
AB  - The ultrasound, computed tomography and magnetic resonance features of
      extracranial nerve tumours are reviewed. Characteristic locations and appearances
      help to define nerve tumours although the imaging findings of nerve and other
      soft tissue tumours overlap.

PMID- 9022576
TI  - Spiral CT and the pre-operative assessment of pancreatic adenocarcinoma.
AB  - AIM: To determine the value of spiral computed tomography (CT) in the pre
      operative assessment of pancreatic carcinoma. PATIENTS AND METHODS: Fifty
      patients with proven pancreatic carcinoma referred for pancreatoduodenectomy
      underwent pre-operative spiral CT using a dedicated pancreatic protocol to
      determine tumour resectability. Twenty-eight patients subsequently underwent
      surgical exploration. RESULTS: Pre-operative imaging suggested that 15 tumours
      were resectable, and macroscopic clearance was complete in 13 giving a positive
      predictive value (PPV) of 87%. PPV of irresectability was 92%. CT underestimated
      locally advanced disease (n = 2), missed small hepatic metastases (n = 1), and
      lymphadenopathy (n = 1). CT overestimated SMV encasement in 1 case, otherwise
      prediction of vascular patency and compromise was correct. The conspicuity of
      small resectable carcinomas was improved by spiral scanning. CONCLUSION: The
      optimised pancreatic parenchymal enhancement and vascular opacification achieved
      by spiral CT improves tumour detection of small carcinomas, allows accurate
      assessment of peripancreatic vessels, and reliably predicts both resectable and
      irresectable disease. CT remains inherently limited in the prediction of early
      extrapancreatic non-vascular spread and of lymphatic metastases.

PMID- 9022575
TI  - Myometrial invasion of endometrial carcinoma: assessment with dynamic MR and
      contrast-enhanced T1-weighted images.
AB  - AIM: To evaluate the usefulness of dynamic magnetic resonance (MR) imaging in
      assessing the depth of myometrial invasion, compared with conventional T2
      weighted and contrast-enhanced T1-weighted imaging. PATIENTS AND METHODS: Forty
      patients with endometrial carcinoma were examined with T2-weighted images,
      dynamic studies and contrast-enhanced T1-weighted images, preoperatively. We
      evaluated enhancement patterns of myometrium and tumour, and compared MR findings
      with histological results concerning the depth of myometrial invasion. RESULTS:
      In assessing the depth of myometrial invasion, the accuracy of T2-weighted
      images, dynamic studies and contrast-enhanced T1-weighted images was 58%, 85% and
      68%, respectively. The tumour-myometrial contrast of dynamic studies was higher
      than that of other images. In addition, subendometrial enhancement (SEE) was
      frequently observed in dynamic studies in post-menopausal women, which was an
      important landmark in detecting myometrial invasion. CONCLUSION: We consider that
      dynamic MR imaging has greater advantage in assessing myometrial invasion than T2
      weighted or contrast-enhanced T1-weighted imaging.

PMID- 9022577
TI  - Effect of HIV status on chest radiographic and CT findings in patients with
      tuberculosis.
AB  - AIM: To compare the chest radiographic and chest CT findings of tuberculosis
      according to HIV status. PATIENTS AND METHODS: Ninety-eight HIV-tested patients
      with cultures positive for Mycobacterium tuberculosis (Mtb) between January 1991
      and December 1993 whose clinical charts and radiographic records were available
      for review formed the study population. There were 67 HIV-positive patients (51
      men, 16 women) and 31 HIV-negative patients (23 men, 8 women). Chest CT scans
      were available for review in 15 HIV-positive and four HIV-negative patients.
      RESULTS: On chest radiographs, HIV-positive patients had mediastinal
      lymphadenopathy (60% vs. 23%) and atypical infiltrates (55% vs. 10%)
      significantly more frequently than HIV-negative patients. Conversely, HIV
      negative patients had infiltrates typical for reactivation tuberculosis (77% vs.
      30%) and cavitation (52% vs. 18%) significantly more frequently than HIV-positive
      patients. The chest CT scans showed a similar trend, but significant differences
      were only seen regarding more frequent bilateral mediastinal lymphadenopathy in
      HIV-positive patients and more frequent cavitation in HIV-negative patients.
      CONCLUSION: This study demonstrates significant differences in chest radiographic
      and chest CT appearances of tuberculosis according to HIV status. HIV-positive
      patients have more frequent atypical infiltrates and mediastinal lymphadenopathy,
      and less frequent cavitation and infiltrates typical for reactivation
      tuberculosis than do HIV-negative patients.

PMID- 9022578
TI  - Arteriovenous shunting in hepatocellular carcinoma: its prevalence and clinical
      significance.
AB  - Arteriovenous shunting has been reported in hepatocellular carcinoma (HCC) and is
      a recognized contraindication to treatment by transcatheter arterial
      chemoembolization. This study aims to determine the prevalence of arteriovenous
      shunting in patients presenting with HCC and the development of shunts in those
      with inoperable HCC being treated with repeated chemoembolization. In a group of
      292 Chinese patients (251 men, 41 women; mean age 54.7 years) presenting with
      HCC, hepatic angiograms demonstrated arteriovenous shunting in 91 cases (31.2%);
      shunting into the portal vein was observed in 84 (28.8%) and shunting into the
      hepatic vein in seven (2.4%). The hepatic angiograms of a separate group of 171
      Chinese patients (144 men, 27 women: mean age 55.4 years) undergoing
      chemoembolization for inoperable HCC were analysed. Arteriovenous shunting
      developed during treatment in 20 patients (11.7%). Of these 20 patients, one had
      shunting into the hepatic vein while 19 (11.1%) had arterioportal shunting.
      Arteriovenous shunting occurred through the tumour or portal vein tumour thrombus
      in 13 patients, and occurred at sites remote from the tumour in the other seven
      patients. Shunting disappeared on repeat angiograms in three patients. Various
      postulated mechanisms responsible for arteriovenous shunting in HCC are reviewed.
      The recognition of development of arteriovenous shunting during chemoembolization
      of HCC is important as it has a direct bearing on patient management and
      prognosis.

PMID- 9022579
TI  - Possibility of differentiating small hyperechoic liver tumours using contrast
      enhanced colour Doppler ultrasonography: a preliminary study.
AB  - We performed a preliminary study to investigate the possibility of
      differentiating small hyperechoic liver tumours, including hepatocellular
      carcinomas (HCCs), haemangiomas and focal fatty lesions, by administering a
      galactose-based contrast agent (SH/TA-508 (Levovist)) during colour Doppler
      ultrasonography (US). Ten patients (age range: 48-81 years) with small liver
      tumours (four HCCs, four hemangiomas and two focal fatty lesions) of less than 20
      mm in diameter presented with hyperechoic masses with no intratumoural colour
      signals on conventional colour Doppler US. All patients subsequently underwent
      colour Doppler US with this contrast agent. Colour Doppler images of the tumours
      were assessed before and after the intravenous injection of 8 ml of the contrast
      agent at a concentration of 400 mg/ml. Prior to injection of the contrast agent,
      no intratumoural colour signals were observed in any cases. After injection,
      intratumoural colour signals appeared in all HCCs and in two haemangiomas with
      tumour-margin enhancement. The enhanced colour signals appeared to be related to
      cardiac contraction in the HCCs, but not in the haemangiomas. In the remaining
      two haemangiomas, only tumour-margin enhancement was observed. In the focal fatty
      lesions, neither intratumoural nor tumour-margin enhancement was observed. These
      results, although preliminary, suggest that the detection of colour Doppler
      signals is improved by using a contrast agent and the differences between
      enhanced colour signals from HCCs and haemangiomas may help differentiate
      hyperechoic HCCs from other hyperechoic tumours, including haemangiomas and focal
      fatty lesions.

PMID- 9022580
TI  - MRI in the investigation of Morton's neuroma: which sequences?
AB  - Morton's 'neuroma' is a painful focus of peri-neural fibrosis, which may affect
      the interdigital nerves of the feet. Clinical diagnosis and localization may be
      inaccurate. Computed tomography (CT), ultrasound and magnetic resonance imaging
      (MRI) have been used to confirm the diagnosis pre-operatively. Recently, MRI
      using T1-weighted sequences with fat saturation after i.v. Gadolinium DTPA has
      been suggested as the most effective MR sequence for depiction of Morton's
      neuroma of the neuroma of the forefoot. Our results show that T1-weighted axial
      and coronal images with an axial FSE T2-weighted sequence detect neuromata more
      consistently than an enhanced T1 fat suppressed sequence.

PMID- 9022581
TI  - Neuro-endoscopic third ventriculostomy: evaluation with magnetic resonance
      imaging.
AB  - We have performed a prospective study of the use of magnetic resonance (MR)
      imaging in 14 patients undergoing neuro-endoscopic third ventriculostomy. MR
      imaging was undertaken prior to the endoscopy and serial studies were carried out
      after the procedure. MR imaging provides important information concerning the
      morphology of the third ventricle and allows the identification of an appropriate
      puncture site in the floor of the third ventricle. In particular, the
      relationship of the third ventricular floor to the basilar artery is well
      demonstrated. Following an endoscopic septostomy, MR imaging allows visualisation
      of any change in ventricular size. A cerebro-spinal fluid (CSF) flow void in the
      anterior inferior third ventricle, sometimes extending into the suprasellar
      cisterns was frequently demonstrated and this was found to be a more constant
      feature than reduction in ventricular size. MR imaging provides an indispensable
      tool for both planning and follow-up of endoscopic third ventriculostomy.

PMID- 9022582
TI  - Clinical audit and standard setting for symptomatic breast imaging in South
      Thames region.
AB  - Audit is recognized as an important part of the UK National Health Service Breast
      Screening programme. This paper describes a simple method of auditing breast
      imaging in symptomatic women which was applied in the South Thames (East) Region
      of England. No appropriate standards were available before this audit started.
      Standards were set at the end of the first cycle by the Regional Radiology Audit
      Committee and these were used in the second cycle of this audit. A comparison
      between hospitals which organize both breast screening and symptomatic imaging
      and those with units providing symptomatic breast imaging only shows no
      significant difference in the accuracy diagnosis and the false negative and false
      positive rates between the two. However non-screening units, are significantly
      more likely to issue an equivocal radiology report (P = 0.000001). Measures to
      reduce the incidence of equivocal reporting, by prospectively issuing an audit
      grade with the report and double reporting of equivocal images are recommended.

PMID- 9022583
TI  - Intravascular contrast media: can we justify the continued use of ionic contrast
      agents?
AB  - Cost has been the major factor preventing the universal conversion to non-ionic
      contrast agents. We assessed the costs and potential benefits of making this
      change in our department. During a 10-month-period the use of all intravascular
      contrast agents and reaction rates were audited prospectively. One thousand three
      hundred and ninety-four examinations were included. A local protocol for the use
      of ionic and non-ionic contrast media was already in place, based on the Royal
      College of Radiologists Guidelines. For each patient the contrast agent used,
      risk factors, and presence or absence of a contrast reaction were recorded. Non
      ionic contrast agent usage exceeded ionic by a factor of 10. Patients receiving
      ionic agents intravenously had a reaction rate of 16.8% compared with 2.7% for
      non-ionic contrast media. The use of ionic contrast media was subsequently
      suspended and the effect of this on overall costs assessed by retrospectively and
      prospectively analysing hospital expenditure on contrast agents. No increase in
      costs was found. The reasons for this are two-fold. Firstly in our institution
      the protocol in place and the nature of the workload resulted in relatively small
      volumes of ionic contrast media being used compared with non-ionic agents.
      Secondly, since our department is a bulk purchaser of non-ionic agents,
      substantial discounts could be negotiated. The benefits of non-ionic contrast
      media are well recognized and our experience suggests that cost may no longer be
      a barrier to conversion to these lower risk agents.

PMID- 9022584
TI  - Retention balloon catheters and barium enemas: attitudes, current practice and
      relative safety in the UK.
AB  - Balloon catheters have been associated with increased morbidity and mortality
      leading some to believe they should be banned, yet others find them both useful
      and safe if used properly. Questionnaires were sent to all Consultant
      Radiologists in the UK to document current practice. Particular attention focused
      on whether eight safety aspects are considered during their use. In this entirely
      retrospective study complications with both balloon and standard tip catheters
      were recorded during the 3-year-period 1992 to 1994 to assess their relative
      safety. Twenty-two percent of UK Radiologists routinely used a rectal balloon.
      This was not associated with any increase in mortality, but extraperitoneal
      rectal perforation was increased by a factor of 2.5. The routine use of retention
      balloon catheters may not be justified.

PMID- 9022585
TI  - MR imaging of segmental renal infarction: an experimental study.
AB  - An experimental study was performed in 12 rabbits to evaluate the magnetic
      resonance (MR) imaging findings of segmental renal infarction. Three or four MR
      examinations were performed at 6 h, 1 day, 3 days, 1 week, 2 weeks, and 4 weeks
      following the ligation of segmental artery of the left kidney. The signal
      intensities of the infarcted area on both T1- and T2-weighted (T1W and T2W,
      respectively) images were lower than those of the non-affected area in the 6 h
      group, and pathological examination showed mild interstitial oedema and
      haemorrhage. The signal intensities of the lesion became higher on T1W images and
      higher or mixed on T2W scans in the 1 day group, in which the pathological
      findings were intense interstitial haemorrhage, interstitial oedema, and early
      coagulative necrosis. The signal intensities of the lesion on both pulse
      sequences were also higher in the 3 day and 1 week groups in which pathological
      examination showed progressive coagulative necrosis. The signal intensities of
      the lesions in the 2 and 4 week groups were lower on both pulse sequences, and
      the pathological finding was organizing fibrosis. Post-contrast T1W images
      demonstrated well the extent of the infarction in all but two cases, in which the
      signal intensities of the lesions were higher on pre-contrast T1W scans.

PMID- 9022586
TI  - Case report: granulocytic sarcoma (GS) presenting as acute cord compression in a
      previously undiagnosed patient.

PMID- 9022587
TI  - Case report: sacral insufficiency fractures masking malignancy.

PMID- 9022588
TI  - Case report: acute radiculopathy due to a haemorrhagic lumbar synovial cyst.

PMID- 9022589
TI  - Case report: magnetic resonance imaging (MRI) appearances of benign schwannoma of
      the larynx.

PMID- 9022590
TI  - PEG--is the E necessary? A comparison of percutaneous and endoscopic gastrostomy.

PMID- 9022591
TI  - True massive thymic hyperplasia.

PMID- 9022592
TI  - Prolactin disorders.
AB  - OBJECTIVE: To review the pathophysiology, clinical manifestations, current
      diagnostic procedures, and treatment options for disorders involving PRL
      production. Common clinical dilemmas are discussed in a pragmatic fashion to
      guide the practitioner. DESIGN: A world literature search of basic sciences and
      medical articles from the last three decades was performed using computerized
      MEDLINE. Recent endocrine and reproductive endocrine textbooks also were
      reviewed. Studies were selected for their degree of contribution to the basic
      sciences and clinical understanding of the disorder and for the quality of their
      study design and content. The information was summarized and grouped according to
      its relevance and application to specific sections of the manuscript. Studies
      were evaluated and critically used to support the views of the authors and to
      suggest specific clinical management strategies. RESULT(S): Disorders derived
      from abnormal PRL production are relatively common in clinical practice.
      Infertility, menstrual disorders, and galactorrhea are the most frequent
      manifestations encountered in women. Although frequently benign, the disorder
      occasionally may have severe consequences. CONCLUSION(S): An understanding of the
      underlying physiology and pathophysiology coupled with the awareness of the
      heterogeneous presentation of this disorder should help the clinician to approach
      it successfully.

PMID- 9022593
TI  - Apoptosis and the ovary: a fashionable trend or food for thought?

PMID- 9022594
TI  - Management of ambiguous genitalia in pseudohermaphrodites: new perspectives on
      vaginal dilation.
AB  - OBJECTIVE: To evaluate vaginal size and sexual activity after different
      techniques of feminization of external genitalia in patients with
      pseudohermaphroditism. DESIGN: Retrospective clinical study. SETTING:
      Pseudohermaphrodite patients seen at our institution. PATIENT(S): Three female
      and 20 male pseudohermaphrodites raised as females. INTERVENTION(S): Bilateral
      orchidectomy, feminization of external genitalia (clitoridectomy or
      clitoroplasty, urogenital sinus enlargement), and/or neovaginoplasty or vaginal
      dilation with acrylic molds. MAIN OUTCOME MEASURE(S): Psychological evaluation,
      vaginal size, and quality of intercourse. RESULT(S): All patients referred sexual
      drive to men. Fifty percent of the patients who were submitted to neovaginoplasty
      referred pain or bleeding during sexual intercourse. On the other hand, 87% of
      the patients who were submitted to vaginal dilation with acrylic molds, after
      genitoplasty or not, referred satisfactory sexual intercourse. All patients who
      were submitted to clitoroplasty referred orgasm and 29% of the patients submitted
      to clitoridectomy referred no orgasm. Of three patients with congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency, two became pregnant and delivered
      normal children through cesarian section. CONCLUSION(S): In pseudohermaphrodites
      with female social sex, surgical correction of external genitalia performed in
      childhood and vaginal dilation with acrylic molds performed when they wished to
      start having sexual intercourse resulted in best outcome.

PMID- 9022595
TI  - Observer variability in the diagnosis and management of the hysterosalpingogram.
AB  - OBJECTIVE: To determine the reproducibility of hysterosalpingogram (HSG)
      interpretation and clinical management recommendations among trained observers.
      DESIGN: Fifty HSG films were distributed to five fertility practitioners with a
      mean of 20 years clinical experience. Each observer evaluated components of
      uterine and tubal status and provided clinical recommendations for hysteroscopy
      and laparoscopy. SETTING: University hospital-affiliated reproductive endocrine
      practice. INTERVENTION(S): None MAIN OUTCOME MEASURE(s): The level of agreement
      among observers for each uterine and tubal category as determined by the
      kappa(kappa) statistic. Determinants of clinical recommendation for further
      diagnostic studies were assessed. RESULT(S): The level of agreement between
      observers as determined by kappa ranged from 0.645 in the hydrosalpinx category,
      indicating fair reliability, to 0.111 for pelvic adhesions, indicating poor
      reliability. The composite kappa for uterine status was 0.345 whereas the
      composite kappa for tubal status was 0.430. Agreement among observers concerning
      management showed marginal reproducibility with a kappa of 0.261. Overall, more
      than one abnormality of either the cavity or the fallopian tubes led to a
      diagnostic recommendation for further workup in > or = 90% of cases.
      CONCLUSION(S): In a group of five experienced clinicians, there was considerable
      variability in the interpretation as well as the clinical management of the HSG.
      Physicians caring for infertile couples should be aware of this discrepancy and
      should, if possible, review carefully both the original films as well as the
      report of the attending radiologist in formulating their diagnostic evaluation
      and management plan.

PMID- 9022596
TI  - Changing trends in the diagnosis of endometriosis: a comparative study of women
      with pelvic endometriosis presenting with chronic pelvic pain or infertility.
AB  - OBJECTIVE: To compare demographic, epidemiologic, and medical data and to
      evaluate diagnostic trends in women with endometriosis and chronic pelvic pain
      symptoms or endometriosis and infertility. DESIGN: Retrospective analysis.
      SETTING: Institute for the Study and Treatment of Endometriosis. PATIENT(S): Six
      hundred ninety-three consecutive patients with endometriosis and chronic pelvic
      pain (n = 357) or endometriosis and infertility (n = 336). INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Demographic and epidemiologic parameters, diagnostic
      trends. RESULT(S): Women with pelvic symptoms were younger, had less formal
      education, more frequent family history, and higher frequency and intensity of
      pelvic complaints. Mean ages at first symptom and diagnosis were lower in the
      pain group, but stage of endometriosis at first diagnosis was more advanced. The
      mean "diagnostic delay" was longer in the pelvic pain than in the infertile group
      (6.35 versus 3.13 years), but it decreased during three consecutive 5-year
      intervals in both groups, and there was also a gradual decrease in the frequency
      of advanced endometriosis at the time of first diagnosis. CONCLUSION(S):
      Demographic and epidemiologic parameters in women with endometriosis differ,
      depending whether chronic pelvic pain or infertility are the presenting symptoms.
      In the pain group, diagnostic delay is longer and endometriosis at diagnostic
      laparoscopy more advanced, indicating progressiveness of the disease. During the
      last 15 years, diagnostic delay steadily decreased and the frequency of advanced
      endometriosis at first diagnosis declined.

PMID- 9022597
TI  - Changes in the menstrual bleeding of users of a subdermal contraceptive implant
      of nomegestrol acetate (Uniplant) do not influence sexual frequency, sexual
      desire, or sexual enjoyment.
AB  - OBJECTIVE: To evaluate the effect of menstrual changes induced by a nomegestrol
      acetate subdermal contraceptive implant (Uniplant; Thermex, Bahia, Brazil) on
      users' sexuality. DESIGN: Prospective observational survey. SETTING: San Borja
      Arriaran Hospital, University of Chile, School of Medicine. PATIENT(S): Normally
      cycling healthy women and their partners. INTERVENTION(S): Structured interview
      before and during use of the contraceptive. MAIN OUTCOMES MEASURE(S): Sexual
      frequency, desire, and enjoyment; perception of health; and contraceptive
      satisfaction. RESULT(S): During the use of the implant more women reported
      irregular cycles (32% versus 11%) and vaginal spotting (38% versus 19%).
      Frequency of sexual relations was unchanged (2.3 versus 2.5/wk) but the percent
      of couples engaging in sexual relations during vaginal spotting increased (28%
      versus 11%). There was no significant difference in the percent of men or women
      who reported an increase, or decrease, in perceived sexual desire, sexual
      enjoyment, or perception of health during the use of Uniplant. CONCLUSION(S):
      Despite the alterations in menstrual cyclicity and the occurrence of spotting,
      the use of a contraceptive subdermal implant of nomegestrol acetate did not
      effect desire for, enjoyment of, or frequency of sexual relations in users.

PMID- 9022599
TI  - Effects of clomiphene citrate on the endometrial thickness and echogenic pattern
      of the endometrium.
AB  - OBJECTIVE: To study the effects of clomiphene citrate (CC) on the endometrium by
      ultrasound and to reveal the echogenic difference between the control cycle and
      the CC cycle. DESIGN: Retrospective study of patients before and during a CC
      treatment. SETTING: Department of Obstetrics and Gynecology, Yamaguchi University
      School of Medicine, Ube, Yamaguchi, Japan. PATIENT(S): Seventy-nine infertile
      women who had a spontaneous ovulation and a normal luteal function.
      INTERVENTION(S): Patients received 50 mg/d CC between days 5 and 9 of the
      menstrual cycle. MAIN OUTCOME MEASURE(S): Endometrial thickness, echogenic
      pattern of the endometrium, serum E2 content, and E2 and P receptor contents in
      the endometrium. RESULT(S): Endometrial thickness was significantly thinner
      during the CC cycle (7.6 +/- 1.4 mm, mean +/- SD, n = 79) than during the control
      cycle (8.5 +/- 1.7 mm, n = 79) on late proliferative days, but there was no
      significant difference on midsecretory days (10.8 +/- 2.2 mm during the CC cycle,
      n = 79; 11.2 +/- 2.2 mm during the control cycle, n = 79). The echogenic
      patterns, however, were different between the two cycles on midsecretory days.
      Moreover, the incidence in which patients showed a grade 3 endometrium on
      midsecretory days was significantly higher during the conceived CC cycle compared
      with the not-conceived CC cycle. Serum E2 levels were significantly higher, but
      E2 receptor contents in the endometrium were significantly lower during the CC
      cycle (67 +/- 46 fmol/mg, n = 13) compared with the control cycle (123 +/- 89
      fmol/mg, n = 15) on late proliferative days. CONCLUSION(S): Clomiphene citrate
      affected the echogenic pattern of the endometrium, and most of the endometrium
      showed a grade 3 pattern on midsecretory days during the conceived CC cycle.
      Under the CC treatment, the comfortable endometrium for embryos might be
      different from the control cycle.

PMID- 9022598
TI  - Neuroendocrine mechanism of anovulation in users of contraceptive subdermal
      implant of nomegestrol acetate (Uniplant).
AB  - OBJECTIVE: To evaluate a nomegestrol acetate subdermal contraceptive implant's
      (Uniplant; Thermex, Monaco) effect on the hypothalamus-pituitary-ovarian axis.
      DESIGN: A prospective clinical trial. SETTING: San Borja-Arriaran Clinical
      Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling
      healthy women. INTERVENTION(S): Insertion of Uniplant. MAIN OUTCOME MEASURE(S):
      Luteinizing hormone pulse and endocrine profiles were assessed before, 48 hours
      after insertion, and after prolonged use of the implant. RESULT(S): Anovulation
      was noted in 100% of users in the first month. Seventy percent of subjects
      demonstrated follicular development with the absence of ovulation and an
      endocrine profile similar to the follicular phase: (LH pulse/8 hours 6.85 +/-
      0.67, LH amplitude 3.54 +/- 0.65 mIU/mL (conversion factor to SI unit, 1.00), and
      E2 193 +/- 29.4 pg/mL (conversion factor to SI unit, 3.67), whereas 30%
      demonstrated no follicular activity with an endocrine profile similar to the
      luteal phase: (LH pulse/8 hours; 3.66 +/- 0.66, LH amplitude 5.76 +/- 1.73
      mIU/mL, and E2 67.5 +/- 4 pg/mL. Clinical characteristics, serum gonadotropin
      concentration, and LH pulse characteristics failed to predict which subjects
      would initiate or remain devoid of follicular activity. CONCLUSION(S): Uniplant
      results in anovulation via two mechanisms: hypothalamic suppression in subjects
      who lack follicular development, and likely suppression of the pituitary LH surge
      in subjects who initiate follicular activity.

PMID- 9022600
TI  - Vascular endothelial growth factor plasma levels correlate to the clinical
      picture in severe ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To assess the potential involvement of vascular endothelial growth
      factor in the hyperpermeability characterizing the ovarian hyperstimulation
      syndrome (OHSS). DESIGN: A controlled clinical study that followed the kinetics
      of vascular endothelial growth factor in the plasma of patients with severe OHSS
      from the time of admission to the hospital and until clinical resolution.
      SETTING: Women hospitalized with severe OHSS in a tertiary medical center.
      PATIENT(S): Seven patients with severe OHSS after ovulation induction for IVF and
      seven controls who had received a similar ovulation induction regimen and did not
      develop the OHSS. INTERVENTION(S): Three blood samples were obtained from each
      OHSS patient: upon hospitalization for severe OHSS, when significant clinical
      improvement was evident, and on the first follow-up visit after the patients'
      discharge. Ascitic fluid was obtained from all OHSS patients by therapeutic
      paracentesis during the active phase of the syndrome. Blood samples were drawn
      from the control patients 4 to 6 days after ET. All samples were assayed for
      vascular endothelial growth factor levels, hematocrit, E2 levels, and white blood
      cell count. MAIN OUTCOME MEASURE(S): Vascular endothelial growth factor levels
      were assayed by ELISA. Estradiol was determined by RIA. RESULT(S): Compared with
      the controls, high levels of vascular endothelial growth factor were detected in
      the plasma of all patients admitted for severe OHSS. Levels dropped significantly
      along with clinical improvement, reaching minimum values after complete
      resolution. A statistically significant correlation was found between plasma
      vascular endothelial growth factor levels and certain biologic characteristics of
      OHSS and of capillary leakage such as leukocytosis and increased hematocrit.
      Ascitic fluid obtained from the study patients also contained high vascular
      endothelial growth factor levels. CONCLUSION(S): These findings suggest the
      involvement of vascular endothelial growth factor in the pathogenesis of
      capillary leakage in the OHSS.

PMID- 9022601
TI  - Localization of laminin, fibronectin, E-cadherin, and integrins in endometrium
      and endometriosis.
AB  - OBJECTIVE: To compare the localization of adhesion proteins (laminin and
      fibronectin) and their receptors of the integrin family in endometriosis and
      endometrium. DESIGN: An immunohistochemical study. SETTING: University Hospital,
      Department of Gynecology and Department of Cell Biology. PATIENT(S): Eighteen
      endometriosis patients undergoing laparoscopy for pain or infertility and nine
      control patients undergoing laparoscopy for sterilization or hysterectomy. MAIN
      OUTCOME MEASURE(S): The expression of adhesion glycoproteins (laminin and
      fibronectin), their receptors alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1,
      alpha 5 beta 1, and alpha 6 beta 1, and E-cadherin was determined by
      immunohistochemistry on frozen sections. RESULT(S): The distribution of both
      adhesive glycoproteins, laminin and fibronectin, and their receptors was
      identical in endometriosis and endometrium. Fibronectin receptors (alpha 4 beta
      1, alpha 5 beta 1) displayed distinct expression patterns in endometrium and
      endometriosis. No endometrial glands showed positive staining for the alpha 5
      chain, whereas this integrin subunit was detected in almost all endometriotic
      lesions. The integrin alpha 4 chain was present in all endometriotic glands but
      was absent from endometrial glands in the proliferative phase of the cycle.
      CONCLUSION(S): No difference in cell adhesion molecule localization nor receptors
      was observed between endometriotic and endometrial samples, except for
      fibronectin receptors. Their expression persisted around endometriotic glands but
      not in endometrium. These results suggest that fibronectin receptors could play a
      role in the persistence of endometriotic lesions, despite menstruation in
      corresponding eutopic endometrium.

PMID- 9022602
TI  - Endothelin levels decrease after oral and nonoral estrogen in postmenopausal
      women with increased cardiovascular risk factors.
AB  - OBJECTIVE: To establish levels of plasma endothelin-1 in postmenopausal women
      with increased CV risk as compared with healthy premenopausal women and to
      measure the effects of different forms of estrogen replacement on plasma
      endothelin-1. DESIGN: Prospective randomized study. SETTING: University of
      Southern California Medical Center. PATIENT(S): We studied 18 postmenopausal
      women (mean age 53.4 +/- 4.9 years) with total cholesterol levels > 240 mg/dL
      divided into those with and without hypertension as well as in 10 healthy
      premenopausal women. INTERVENTION(S): The postmenopausal women were randomized to
      receive oral estrone sulfate, transdermal E2, or placebo for 30 days. MAIN
      OUTCOME MEASURE(S): We measured the endothelin-1 levels and total cholesterol at
      baseline and after 30 days of estrogen treatment. RESULT(S): In the
      postmenopausal women, endothelin-1 was higher (4.58 +/- 0.46 pg/mL) compared with
      premenopausal levels (2.80 +/- 0.46 pg/mL). In hypertensive postmenopausal women,
      endothelin-1 was 5.56 +/- 0.44 pg/mL. After estrogen, plasma endothelin-1 values
      decreased from 5.38 +/- 0.66 to 4.82 +/- 0.9 pg/mL with oral estrone sulfate,
      4.84 +/- 0.25 to 4.54 +/- 0.49 pg/mL with transdermal E2, and did not change
      after placebo 4.76 +/- 0.71 to 4.81 +/- 0.46 pg/mL. In evaluating hypertensive
      women alone with estrogen therapy, plasma endothelin-1 showed the greatest
      decrement from 5.39 +/- 0.49 to 4.4 +/- 0.59 pg/mL (18.4%). The decrease in
      endothelin-1 with estrogen, which was statistically significant for the entire
      group, did appear to be influenced by the route of administration. Baseline
      plasma endothelin-1 levels were correlated positively to plasma cholesterol
      levels with a correlation coefficient of 0.632. CONCLUSION(S): These data provide
      another potential mechanism explaining the cardioprotective effects of hormone
      replacement therapy.

PMID- 9022603
TI  - A prospective, randomized study to assess the tolerance and efficacy of
      intramuscular and subcutaneous administration of recombinant follicle-stimulating
      hormone (Puregon).
AB  - OBJECTIVE: To compare local tolerance and clinical efficacy after i.m. or s.c.
      injection of recombinant FSH (Puregon; NV Organon, Oss, The Netherlands). DESIGN:
      An open-label, prospective, randomized, group-comparative, multicenter study.
      SETTING: Twelve IVF clinics in 10 countries. PATIENT(S): Two hundred eighteen
      infertile pituitary-suppressed women undergoing IVF-ET were randomized, of whom
      195 (i.m., n = 77; s.c., n = 118) received recombinant FSH. INTERVENTION(S): One
      cycle of controlled ovarian hyperstimulation induced by either i.m. or s.c.
      injection of recombinant FSH, followed by IVF-ET. MAIN OUTCOME MEASURE(S): Local
      tolerance symptoms, number of oocytes retrieved, ongoing pregnancy rate.
      RESULT(S): The incidences after i.m. injection of bruising, pain, redness,
      swelling, and itching were 37.7%, 31.2%, 13.0%, 7.8%, and 6.5%; after s.c.
      injection, the corresponding figures were 54.2%, 28.0%, 16.1%, 5.9%, and 3.4%.
      Only bruising was significantly lower in the i.m. group, which could be
      attributed to the more visible superficial injection site with s.c.
      administration. The overall occurrence of local symptoms were 63.6% after i.m.
      injection and 68.6% after s.c. injection. The mean numbers of oocytes recovered
      were 9.8 (i.m) and 10.4 (s.c.) and the ongoing pregnancy rates per attempt were
      27.1% (i.m.) and 26.1% (s.c.), respectively. CONCLUSION(S): There were no marked
      differences in local tolerance symptoms and clinical efficacy between i.m. and
      s.c. administration of recombinant FSH.

PMID- 9022604
TI  - Follow-up of a cohort of 422 children aged 6 to 13 years conceived by in vitro
      fertilization.
AB  - OBJECTIVE: To contact the total cohort of children conceived by IVF-ET
      consecutively in our center between June 1981 and December 1988. DESIGN:
      Retrospective study. SETTING: Infertility unit of the department of Obstetrics
      and Gynecology, Antoine Beclere Hospital, Clamart, France. PATIENT(S): Complete
      information was obtained on 370 children. The percentage lost for follow-up was
      9%. INTERVENTION(S): To assess the children's well-being, telephone interviews of
      the parents and questionnaires sent to the parents and/or pediatrician were used.
      MAIN OUTCOME MEASURE(S): Surgical procedures, malformation, height and weight,
      school performance. RESULT(S): The physical growth of these children showed no
      major pathological features, with only 2.2% of them being below 2 SD for weight
      and 0.3% for height. The rates of malformation were not significantly different
      between these children and the general population. School performance was good,
      with 92.2% presenting encouraging outcome. Fifty-eight percent of the parents of
      children aged 6 to 10 years old did not inform their children about the IVF nor
      did 34% of the parents of children aged 11 to 13. Subsequent to the birth of the
      IVF child, 30 patients (8.9%) had a spontaneous pregnancy. However, five of them
      (15.1%) were ectopic. CONCLUSION(S): This study reports, for the first time,
      reassuring data on the long-term assessment of a large group of older IVF-ET
      children conceived consecutively, with a low percentage of subjects lost for
      follow-up.

PMID- 9022605
TI  - A triplet pregnancy after in vitro fertilization is a procedure-related
      complication that should be prevented by replacement of two embryos only.
AB  - OBJECTIVE: To investigate whether the incidence and obstetric outcome of triplet
      pregnancies after IVF treatment justify strict limitation of the number of
      embryos to be replaced to two. DESIGN: Retrospective analysis. SETTING: A
      transport IVF program. PATIENT(S): All patients who had more than one embryo
      replaced. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Obstetric outcome,
      pregnancy. RESULT(S): High-order pregnancies occurred in 24 cases (23 triplets
      and 1 quadruplet). Three patients opted for selective embryo reduction (12.5%).
      Three triplet pregnancies spontaneously reduced to twins. Comparison of 18
      triplets, reaching at least 20 weeks' gestation, with 54 twin pregnancies shows a
      higher perinatal mortality in the triplet group, causing 6 out of 18 patients to
      be confronted with at least one perinatal death. Triplets were born at a lower
      gestational age, had a lower birth weight, and a higher hospital admission rate
      of longer duration. Replacement of two, three, or four embryos did not lead to
      differences in pregnancy rates in the population studied. When a pregnancy
      occurred after replacement of three embryos, the risk of having a triplet
      pregnancy was 7.5%. CONCLUSION(S): The obstetric outcome of triplet pregnancies
      in our population indicates that triplet pregnancies after IVF treatment have to
      be prevented. Selective embryo reduction is acceptable for few patients only and
      can therefore not be seen as a solution. Replacement of three embryos results in
      triplet pregnancy in an unacceptably high percentage. Replacement of two embryos
      only gives acceptable IVF results and is the method chosen in the IVF program in
      Rotterdam to prevent triplet pregnancies.

PMID- 9022606
TI  - Progesterone levels on the day of human chorionic gonadotropin do not predict
      pregnancy outcome from the transfer of fresh or cryopreserved embryos from the
      same cohort.
AB  - OBJECTIVE: To analyze the differences in pregnancy rates (PRs) from the transfer
      of fresh and cryopreserved embryos from the same cohort of oocytes based on serum
      P levels on the day of hCG administration and the day after. DESIGN:
      Retrospective analysis. SETTING: Infertility patients stimulated for IVF-ET in an
      academic center. PATIENT(S): Three hundred thirty-three patients with fresh
      transfer and at least one transfer of cryopreserved embryos from the same cohort
      of recruited oocytes. All stimulations were down-regulated with a GnRH agonist in
      a long protocol before gonadotropin stimulation. MAIN OUTCOME MEASURE(S):
      Clinical PR. RESULT(S): The clinical PR in fresh cycles was 24% for the P < or =
      0.9 ng/mL group (group A; conversion factor to SI unit, 3.18) and 34% for the P >
      0.9 ng/mL group (group B). Group B patients were younger, received fewer ampules
      of gonadotropins, had higher peak E2 levels, and had more mature oocytes. There
      were no significant differences in the P levels on the day of hCG between
      patients who conceived in both fresh and cryopreserved cycles and any other
      combination of pregnancy outcome sequence. CONCLUSION(S): These findings suggest
      that serum P level cutoffs, on the day of hCG and the day after, as a means of
      making clinical decisions with respect to cancelling the fresh transfer and
      cryopreservation of all embryos for future transfer should be questioned.

PMID- 9022607
TI  - Incidence of apoptotic bodies in membrana granulosa of the patients participating
      in an in vitro fertilization program.
AB  - OBJECTIVE: To investigate the incidence of apoptotic bodies in mural granulosa
      cell masses and cumulus cell masses. DESIGN: Nonrandomized, prospective study.
      SETTING: Department of Obstetrics and Gynecology, Yamagata University School of
      Medicine, Yamagata, Japan. PATIENT(S): One hundred twenty-nine normally ovulating
      women underwent ovulation induction for IVF-ET with GnRH analogue (GnRH-a) and
      gonadotropins. INTERVENTION(S): Patients underwent follicle aspiration after the
      administration of hCG. MAIN OUTCOME MEASURE(S): The nuclei of recovered granulosa
      cells were examined by fluorescence microscopy and the incidence of apoptotic
      bodies was tabulated. RESULT(S): The incidence of apoptotic bodies was
      significantly higher in mural granulosa cell masses than in cumulus cell masses
      in the entire group of 129 patients. Both incidence of apoptotic bodies of mural
      granulosa cell masses and cumulus cell masses were significantly higher in
      patients with less than six follicular oocytes compared with patients with six or
      more oocytes. Nonpregnant patients showed significantly higher incidence of
      apoptotic bodies in mural granulosa cell masses compared with pregnant patients.
      CONCLUSION(S): These results indicate that mural granulosa cell masses and
      cumulus cell masses may have different functions in follicular maturation. The
      incidence of apoptotic bodies in mural granulosa cell masses can be used as an
      indicator of success of IVF.

PMID- 9022608
TI  - An increased vulnerability to stress is associated with a poor outcome of in
      vitro fertilization-embryo transfer treatment.
AB  - OBJECTIVE: To evaluate the association between the vulnerability to stress and
      the treatment outcome of couples undergoing IVF-ET. DESIGN: Controlled,
      prospective clinical study. SETTING: The Assisted Reproduction Unit of the
      Department of Obstetrics and Gynecology, University of Modena. PATIENT(S): Forty
      nine infertile women consecutively admitted to standard superovulation treatment.
      Mean age was 33.9 years, duration of infertility was 6.3 years. Reasons for
      assisted reproduction were mechanical factor in 22 cases, sperm problem in 9
      cases, and endocrine disorder in 6 cases. In 12 cases, infertility was
      unexplained. More than 55% already had an IVF-ET attempt. INTERVENTION(S): The
      day of oocyte pick-up, subjects were submitted to Stroop Color and Word test, a
      task measuring the ability to cope with a cognitive stressor, involving
      attentional and sympathoadrenal systems. Systolic (SBP) and diastolic blood
      pressure, as well as heart rate (HR) were measured at baseline, during the test,
      and 10 minutes after the end of testing. MAIN OUTCOME MEASURE(S): The evidence of
      a biochemical pregnancy (beta-hCG value 12 days after ET) define the success and
      failure groups. RESULT(S): Sixteen women (33%) had a biochemical pregnancy, 12
      also had ultrasound evidence. Eight gave birth to healthy infants. Age,
      education, causes, and duration of infertility were similar in the success and
      failure groups. The latter were more involved in a job outside home than the
      former. Moreover, they had a lower number of both fertilized oocytes and
      transferred embryos. In response to the Stroop test, every subject reported an
      increase of cardiovascular parameters. However, women becoming pregnant showed a
      lower response of both SBP and HR than women who failed. CONCLUSION(S): Both a
      major cardiovascular vulnerability to stress and working outside home are
      associated to a poor outcome of IVF-ET treatment.

PMID- 9022609
TI  - Induction of acrosome reaction in human spermatozoa accelerates the time of
      pronucleus formation of hamster oocytes after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To assess the relationship between the incidence of acrosome reaction
      (AR) and the timing of pronucleus (PN) formation after intracytoplasmic sperm
      injection (ICSI). DESIGN: Prospective study. SETTING: Infertility Research
      Center, Jeil Women's Hospital. MAIN OUTCOME MEASURE(S): Human semen obtained from
      fertile donors was prepared by one of the following methods: washing only (washed
      control); Percoll gradient; pentoxifylline; human follicular fluid (FF);
      pentoxifylline + FF; or platelet-activating factor (PAF) treatment. The AR of
      each group was assessed by fluorescein isothiocyanate-conjugated Pisum sativum
      agglutinin or Arachis hypogea agglutinin. Spermatozoa of washed control,
      pentoxifylline + FF, and PAF treated groups, with significantly higher AR rate
      than others, were injected into mature hamster oocytes. Spermatozoon-injected
      oocytes were cultured for 6, 9, 12, or 15 hours. Then they were stained with
      Toluidine blue for PN formation examination under a light microscope. RESULT(S):
      Acrosome reaction rates of washed control, Percoll gradient, pentoxifylline, FF,
      pentoxifylline + FF, and PAF treated groups were 10.5% +/- 2.6%, 10.3% +/- 1.7%,
      16.4% +/- 1.8%, 24.8% +/- 5.6%, 28.4% +/- 3.8%, and 33.3% +/- 5.2%, respectively.
      Pronuclear formation rate in washed control, pentoxifylline + FF, and PAF treated
      groups were 5.6% (3/54), 19.0% (11/58), and 18.9% (10/53) at 6 hours; 32.7%
      (18/55), 51.8% (29/56), and 57.4% (31/54) at 9 hours; 36.1% (22/61), 53.6%
      (30/56), and 50.0% (27/54) at 12 hours; and 47.2% (25/53), 64.8% (35/54), 53.6%
      (30/56) at 15 hours after ICSI. Pronuclear formation rate was significantly
      higher in pentoxifylline + FF, and PAF treated groups than that in the washed
      control group at 6 and 9 hours after ICSI. CONCLUSION(S): Pronuclear formation of
      oocytes takes place faster on those that were injected with acrosome-reacted
      spermatozoon than those injected with acrosome-intact spermatozoon. It could be
      concluded that induction of the AR of spermatozoa accelerates the time of PN
      formation and early development of the embryo in ICSI.

PMID- 9022610
TI  - Potential enhancement of endometrial receptivity in cycles using controlled
      ovarian hyperstimulation with antiprogestins: a hypothesis.
AB  - OBJECTIVE: To manipulate the luteal endometrial progression by the use of
      antiprogestins. DESIGN: Prospective controlled clinical trial. SETTING: The IVF
      program of the University of Southern California School of Medicine, Los Angeles,
      California. PATIENT(S): Thirteen oocyte donors and 20 oocyte recipients.
      INTERVENTION(S): Controlled ovarian hyperstimulation of oocyte donors,
      administration of two doses of 2.5 mg of RU486 to the study group, and
      endometrial biopsies. MAIN OUTCOME MEASURE(S): Serum E2 and P levels, histologic
      dating of the endometrium, endometrial ultrastructure by scanning electron
      microscopy. RESULT(S): No difference in serum E2 or P levels was noted after
      RU486 administration. The histologic dating was advanced in oocyte donors as
      compared with recipients undergoing artificial cycles but returned to normal (in
      phase) after RU486. Pinopods were noted in all recipient biopsies and in donors
      treated with RU486 but in only one of four biopsies in donor controls.
      CONCLUSION(S): Cycles with controlled ovarian hyperstimulation are associated
      with high early luteal P levels and advanced endometrial histology. Low doses of
      RU486 may correct the precocious luteinization and restore endometrial
      receptivity.

PMID- 9022611
TI  - Effects of cancer on spermatozoa quality after cryopreservation: a 12-year
      experience.
AB  - OBJECTIVE: To determine whether type of cancer and response to treatment was
      related to prefreeze or post-thaw semen quality and to predict post-thaw sperm
      motility from prefreeze motility. DESIGN: Retrospective study. SETTING: Tertiary
      care institution. PATIENT(S): One hundred six cancer patients cryopreserving
      their semen specimens. INTERVENTION(S): Computer-assisted semen analysis was
      performed before and after cryopreservation on each patient specimen. MAIN
      OUTCOME MEASURE(S): The relationship of sperm motility and motion characteristics
      to type of cancer and patient's response to treatment. RESULT(S): Prefreeze and
      post-thaw semen quality did not differ between patients presenting with
      testicular cancer and Hodgkin's disease. Patients with leukemia or advanced soft
      tissue cancer had a higher prefreeze and post-thaw motility and higher total and
      motile sperm count than testicular and Hodgkin's disease patients. A prefreeze
      sperm motility of > or = 15% could predict a post-thaw motility of > 10%.
      CONCLUSION(S): Prefreeze or post-thaw semen quality in cancer patients is not
      affected (except the prefreeze motile sperm count within the testicular cancer
      patients) by the type of disease. Prefreeze motility can predict post-thaw
      motility. Cryopreservation of semen should be offered to cancer patients
      irrespective of the type of disease.

PMID- 9022612
TI  - Persistence or reappearance of nonmotile sperm after vasectomy: does it have
      clinical consequences?
AB  - OBJECTIVE: To determine the percentage of patients with nonmotile sperm 12 weeks
      after vasectomy, to estimate the time needed for eventual azoospermia in these
      patients, and to record the percentage of patients with recurrence of nonmotile
      sperm after initial azoospermia after vasectomy. DESIGN: A review of the semen
      analysis of vasectomies performed in a 2-year period. Semen analysis in a group
      of volunteers from 4 months until 24 months after vasectomy. SETTING: Vasectomies
      performed in an outpatient department of the University Hospital of Maastricht.
      PATIENT(S): Men referred by the general practitioner for a vasectomy.
      INTERVENTION(S): Vasectomy. MAIN OUTCOME MEASURE(S): Amount and motility of sperm
      in postvasectomy semen samples. RESULT(S): Nonmotile sperm was found in 33% of
      the patients 12 weeks after vasectomy. The mean time to azoospermia was 6.36
      months. Nonmotile sperm after initial azoospermia was found in 5 of 65 patients.
      CONCLUSION(S): Azoospermia as a criterion for sterility leads to unnecessary
      prolonged semen analysis in a large percentage of the vasectomized patients.
      Reappearance of nonmotile sperm was found in an unexpectedly high percentage.

PMID- 9022613
TI  - A potential role for cadmium in the etiology of varicocele-associated
      infertility.
AB  - OBJECTIVE: To determine whether mannose ligand receptor and acrosome reaction
      deficits in sperm from men with varicocele are related to the transition metal
      content of their semen. DESIGN: Cadmium and zinc in semen and blood plasma were
      assayed for fertile males, men without varicocele who required intracytoplasmic
      sperm injection to achieve fertilization, and men evaluated for potential
      varicocele-associated infertility. The relationship between actin cytoskeletal
      distributions and acrosome status was determined for fertile donor sperm in the
      presence and absence of exogenous cadmium. SETTING: University hospital-based
      molecular biology research laboratory. PATIENT(S): Patients from two university
      hospital-based IVF-assisted reproductive technology programs and two male urology
      private practices. INTERVENTION(S): Fertile donor sperm were exposed to exogenous
      cadmium during capacitating incubations followed by culture at temperatures up to
      41 degrees C. MAIN OUTCOME MEASURE(S): Metal ion levels in semen and blood plasma
      were determined by graphite furnace atomic absorption spectroscopy. Motile sperm
      were examined for mannose ligand binding and the ability to undergo spontaneous
      and induced acrosome reactions. Unfixed, Triton-permeabilized sperm were probed
      with antiactin and antimyosin antibodies. RESULT(S): Cadmium was elevated and
      zinc was decreased in the seminal plasma of men with varicocele. The content of
      these metals in semen and blood was not correlated. Cadmium exposure in vitro
      reduced mannose receptor expression, acrosome exocytosis, and cytoskeletal
      formation by fertile donor sperm. CONCLUSION(S): Defects in transition metal
      regulation or excessive cadmium exposure are involved in varicocele-associated
      infertility.

PMID- 9022614
TI  - Field trial of a diluent for the transportation of human semen at ambient
      temperatures.
AB  - OBJECTIVE: To examine the ability of a citrate-yolk buffer extender to preserve
      human semen samples at ambient temperatures over a 25- to 30-hour period. DESIGN:
      Human semen samples were diluted 1:1 with citrate-yolk buffer or homologous
      seminal plasma and transported at ambient temperature between two distant
      locations (London to Edinburgh, United Kingdom). Various criteria of semen
      quality then were assessed before and after 25 to 30 hours storage and
      transportation in these diluents. SETTING: An institutional research laboratory
      and a private fertility clinic. PATIENT(S): Samples were provided by 21 donors of
      unknown fertility and 7 asthenozoospermic patients. INTERVENTION(S): The diluent
      used to preserve human semen comprised an egg yolk buffer supplemented with
      fructose and citrate. MAIN OUTCOME MEASURE(S): Aspects of semen quality assessed
      included movement, hyaluronate penetration, viability, acrosome reaction, and
      reactive oxygen species generation. RESULT(S): The deterioration of semen quality
      at ambient temperatures could be prevented by the presence of citrate-yolk
      buffer, permitting the accurate analysis of oxidative stress and human sperm
      function, 25 to 30 hours postejaculation. CONCLUSION(S): Citrate-yolk buffer
      offers considerable promise as a medium for the ambient temperature storage and
      transportation of human semen.

PMID- 9022615
TI  - Autoimmunogenicity of the human sperm protein Sp17 in vasectomized men and
      identification of linear B cell epitopes.
AB  - OBJECTIVE: To assess whether human sera positive for antisperm antibodies have
      detectable levels of Sp17 autoantibodies and to determine the linear B cell
      epitopes to which these are raised for both native and recombinant Sp17. DESIGN:
      Enzyme-linked immunoaborbent assays were performed against recombinant HSp17 on
      15 serum samples from prevasovasostomy and postvasovasostomy patients. Positive
      sera then were used in mimotope analyses to determine HSp17 immunodominant linear
      B cell epitopes. These were compared with the linear B cell epitopes of
      recombinant HSp17. SETTING: University research laboratory. PATIENT(S): Fifteen
      vasectomized or vasovasostomized men. MAIN OUTCOME MEASURE(S): Serum antibody
      reactivity to human Sp17. RESULT(S): Sera from vasectomized and vasovasostomized
      men exhibit Sp17 antibodies raised predominantly to two immunodominant linear B
      cell epitopes (amino acids 4 to 19 and amino acids 118 to 127), which differed
      from those of recombinant HSp17 (amino acids 52 to 79 and amino acids 124 to
      136). CONCLUSION(S): The results show that Sp17 is an antigen to which
      vasectomized men raise autoantibodies. Two linear B cell epitopes predominate in
      native Sp17 and these differ from (but overlap with) those of the bacterially
      expressed recombinant protein.

PMID- 9022616
TI  - Selectivity of the human sperm-zona pellucida binding process to sperm head
      morphometry.
AB  - OBJECTIVE: To obtain quantitative measures of morphometric selectivity of the
      human spermzona pellucida binding process as determined by light microscopy.
      DESIGN: Fully automated sperm head morphometric based on a 32-dimensional
      parameterization of images of Shorr-stained sperm. Zona pellucida selected sperm
      removed from reinseminated oocytes that previously failed IVF. SETTING: Academic
      research group associated with a tertiary infertility service. PATIENT(S): Semen
      samples from 51 infertile patients. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Differences in morphometric parameter means observed before and after
      swim-up and binding to zonae pellucidae. RESULT(S): Significant differences
      between insemination and bound sperm were observed in 17 parameter means and 21
      standard deviations. The sperm-zona pellucida binding process preferentially
      selects sperm heads with a large anterior region with relatively low optical
      density, as well as high axial symmetry and minimal neck anomalies. Bias against
      sperm with pyriform morphology was not observed. CONCLUSION(S): A causal link has
      been established between sperm head morphometry, particularly within the
      acrosomal region, and the ability of sperm to bind to the human zona pellucida.
      As sperm-zona binding is necessary for fertility, it is possible to derive a
      physiologically based assessment for clinical diagnosis of male infertility using
      the "zona-preferred" morphometry results.

PMID- 9022617
TI  - Mouse in vitro fertilization, embryo development and viability, and human sperm
      motility in substances used for human sperm preparation for assisted
      reproduction.
AB  - OBJECTIVE: To investigate the endotoxin content and effects on mouse IVF and
      embryo development and human sperm motility of human sperm separation substances.
      DESIGN: One-cell and zona-free two-cell mouse embryo bioassays and Limulus
      Amoebocyte Lysate endotoxin tests and mouse oocyte parthenogenetic activation,
      IVF, preimplantation and postimplantation embryo development, and human sperm
      motility were performed in control medium or medium containing Percoll, Nicodenz,
      or the washings from Sperm Prep sephadex columns. SETTING: Research Laboratories,
      Sinai Hospital of Baltimore, Baltimore, Maryland. MAIN OUTCOME MEASURE(S):
      Endotoxin levels, embryo development, and sperm motility. RESULT(S): Mouse embryo
      bioassays indicated negative endotoxin levels in Percoll and Nicodenz but Limulus
      Amoebocyte Lysate assays had positive gel formation. Mouse IVF and
      preimplantation development was equivalent in control and Percoll- and Nicodenz
      containing medium; none had parthenogenetic properties but postimplantation
      development was reduced for embryos grown in the presence of Percoll or Nicodenz.
      Human sperm remained motile in the presence of Percoll or Nicodenz. Sperm Prep
      column washes were toxic to mouse gametes and embryos and human sperm and had gel
      formation with the Limulus Amoebocyte Lysate assay. CONCLUSION(S): Percoll and
      Nicodenz, but not Sperm Prep sephadex column washes, were compatible with mouse
      preimplantation and postimplantation embryo development and human sperm motility.

PMID- 9022618
TI  - Comparison of the ultrasonic scalpel to CO2 laser and electrosurgery in terms of
      tissue injury and adhesion formation in a rabbit model.
AB  - OBJECTIVE: To determine the relative effect of an ultrasonic scalpel on
      reproductive tissue compared with CO2 laser and electrosurgery. DESIGN:
      Prospective, randomized animal study. SETTING: University laboratory setting.
      ANIMALS: Sixteen New Zealand White rabbits. INTERVENTION(S): A steel scalpel, an
      ultrasonic scalpel, a CO2 laser, or electrosurgery were used to perform an
      ovarian wedge resection and to remove the distal uterine horn. A 3-cm
      longitudinal incision also was made in the uterine horn. MAIN OUTCOME MEASURE(S):
      The number of 1-second bursts of needle-tip electrosurgery required for
      hemostasis, the depth and degree of coagulation necrosis, degree of fibrin
      deposition, and postoperative adhesion formation. RESULT(S): The amount of
      electrosurgery needed to achieve hemostasis was less for any of the four power
      techniques than for the steel scalpel, with the exception of the ultrasonic
      scalpel at level 5 when used on the ovary. The depth (range: 0.30 to 0.38 mm) and
      the degree of coagulation necrosis was not different for any of the power
      techniques. The fibrin score was greatest for the ultrasonic scalpel at level 5
      in both the ovarian tissue and the uterine tissue. There was no difference in
      adhesion scores for the power techniques and the steel scalpel. CONCLUSION(S):
      The ultrasonic scalpel at level 3 is not different from either CO2 laser or
      electrosurgery in terms of hemostatic properties, coagulation necrosis, or
      adhesion formation in the rabbit model.

PMID- 9022619
TI  - Congenital absence of the uterus and vagina is not commonly transmitted as a
      dominant genetic trait: outcomes of surrogate pregnancies.
AB  - OBJECTIVE: To determine the inheritance pattern of congenital absence of the
      uterus and vagina in affected women undergoing surrogacy IVF with this disorder.
      DESIGN: Retrospective study. SETTING: A hospital-based reproductive endocrinology
      and infertility center. PATIENT(S): Women diagnosed with congenital absence of
      the uterus and vagina undergoing IVF with subsequent transfer of embryos to a
      surrogate uterus. INTERVENTION(S): Questionnaires were sent to all infertility
      treatment centers performing surrogate procedures. MAIN OUTCOME MEASURE(S):
      Number, gender, and frequency of congenital anomalies in progeny. RESULT(S):
      Thirty-two of 53 surveyed programs responded (60%). One hundred sixty-two IVF
      cycles were performed, and 34 liveborn children were delivered (half female). No
      congenital anomalies were found, except for one male child with a middle ear
      defect and hearing loss. CONCLUSION(S): These results strongly suggest that
      congenital absence of the uterus and vagina, if genetically transmitted, is not
      inherited commonly in a dominant fashion.

PMID- 9022620
TI  - Effective treatment of severe menstrual migraine headaches with gonadotropin
      releasing hormone agonist and "add-back" therapy.
AB  - OBJECTIVE: To determine the efficacy of treating women with severe menstrual
      migraine headaches with GnRH agonist (GnRH-a) therapy, alone and combined with
      continuous estrogen-progestin "add-back." DESIGN: Nonrandomized, prospective
      treatment study. SETTING: Outpatient clinic in a university medical center.
      PATIENT(S): Five women who had repetitive, severe, migraine headaches limited to
      the perimenstrual period were selected carefully. INTERVENTION(S): After 2 months
      of basal evaluation, all subjects received GnRH-a (leuprolide acetate depot
      formulation, 3.75 mg IM, monthly) for 10 months. Beginning with the 5th month,
      "add-back" therapy (the addition of transdermal E2, 0.1 mg daily, and oral
      medroxyprogesterone acetate, 2.5 mg daily) was initiated. MAIN OUTCOME
      MEASURE(S): Patients rated headache severity from 0 (absent) to 3 (severe) each
      day; these were combined each month to obtain a cumulative score for that month.
      In addition, patients were asked their overall assessment of the treatments.
      RESULT(S): The mean headache scores for the GnRH-a treatment months (4.0 +/- 1.5,
      mean +/- SEM) and for the GnRH-a and "add-back" treatment months (3.1 +/- 0.7)
      were each significantly lower than those of the control months (15.3 +/- 2.4).
      The patients uniformly found both treatments to be well tolerated and near
      curative for their condition. CONCLUSION(S): Gonadotropin-releasing hormone
      agonist administration, alone or with "add-back" therapy, is a very effective
      treatment for carefully selected patients with severe, perimenstrual migraine
      headaches.

PMID- 9022621
TI  - Ovarian resistance to luteinizing hormone: a novel cause of amenorrhea and
      infertility.
AB  - OBJECTIVE: To report the clinical, hormonal, and histopathological features of a
      woman with ovarian resistance to LH. DESIGN: Clinical study. SETTING: University
      hospital. PATIENT(S): A woman with amenorrhea, sister of a patient with male
      pseudohermaphroditism due to Leydig cell hypoplasia. INTERVENTION(S): Blood
      drawing before and after GnRH stimulation and also after dexamethasone and hCG
      administration, pelvic ultrasound, and ovarian biopsy. MAIN OUTCOME MEASURE(S):
      Karyotype, gonadotropin and steroid measurements, follicular diameter, ovarian
      histology, and sequencing of the LH receptor gene. RESULT(S): Patient had normal
      female external genitalia, normal breast development at puberty, rare episodes of
      vaginal bleeding, and infertility. The karyotype was 46,XX. She had elevated
      serum LH levels, whereas E2 and P concentrations were in the range seen in the
      early follicular phase. Pelvic ultrasound revealed a slightly hypoplastic uterus
      and enlarged polycystic ovaries. A normal follicular reserve for age, antral
      follicles, and absence of corpora lutea or albicans were observed on ovarian
      biopsy. Exon 11 of the LH receptor gene had a normal sequence. CONCLUSION(S): In
      our patient with ovarian resistance to LH, FSH stimulated follicular development
      until the preovulatory stage, but E2 levels remained in the early follicular
      phase range, still sufficient for normal pubertal feminization. Apparently, LH is
      necessary for ovulation and corpus luteum formation.

PMID- 9022622
TI  - An ectopic pregnancy developing in a previous caesarian section scar.
AB  - OBJECTIVE: To report the diagnosis and management of an ectopic pregnancy (EP)
      developing in a caesarean section scar. DESIGN: Case report. SETTING: University
      medical school. PATIENT(S): A patient with a previous history of two caesarean
      sections developing an EP. INTERVENTION(S): Methotrexate (MTX) was administered
      locally under ultrasonographic guidance. MAIN OUTCOME MEASURE(S): Weekly
      screening of blood hCG levels and yolk sac resorption by endovaginal sonography.
      RESULT(S): The diagnosis was suspected by vaginal echography and confirmed by
      magnetic resonance imaging. Local injection of KCl and MTX provoked a progressive
      resorption of the pregnancy. Human chorionic gonadotropin was undetectable on day
      82. CONCLUSION(S): To prevent uterine rupture in cases of an EP developing in a
      caesarean section scar, a medical approach can be proposed.

PMID- 9022623
TI  - What is the radiation exposure to patients during a gynecoradiologic procedure?
AB  - OBJECTIVE: To evaluate the risk of radiation exposure to infertility patients
      during a gynecoradiologic procedure. DESIGN: Retrospective clinical study.
      SETTING: Medical school-affiliated infertility center. PATIENT(S): Three hundred
      thirty-two consecutive infertility patients undergoing a gynecoradiologic
      procedure. INTERVENTION(S): Patients underwent a gynecoradiologic procedure as
      part of their infertility workup and the fluoroscopic exposure time was analyzed.
      MAIN OUTCOME MEASURE(S): The fluoroscopic exposure (rad time) during
      gynecoradiologic procedures, including hysterosalpingogram (HSG), selective
      salpingography, tubal catheterization, and others. RESULT(S): The rad time (mean
      +/- SD) was 63 +/- 54 seconds for normal HSG (n = 94, range 17 to 404 seconds),
      100 +/- 61 seconds for abnormal HSG (n = 53, range 28 to 272 seconds), 111 +/- 57
      seconds for unilateral selective salpingography (n = 36, range 31 to 324
      seconds), 142 +/- 74 seconds for bilateral selective salpingography (n = 87,
      range 40 to 430 seconds), 176 +/- 77 seconds for unilateral tubal catheterization
      (n = 27, range 70 to 342 seconds), and 239 +/- 82 seconds for bilateral tubal
      catheterization (n = 30, range 110 to 381 seconds). Five patients had other
      procedures, such as lysis of intrauterine adhesions (n = 2) and resection of an
      uterine septum (n = 3), for which the rad time was in a range of 180 to 300
      seconds. CONCLUSION(S): The radiation exposure of patients during a
      gynecoradiologic procedure, using previously described standard techniques, is
      well within established margins of safety.

PMID- 9022625
TI  - The disappearing Y chromosome--"I told you so!".

PMID- 9022624
TI  - Ability of an anti-luteinizing hormone-releasing hormone vaccine to inhibit
      gonadotropins in postmenopausal women.
AB  - OBJECTIVE: To determine the effects of immunization with an anti-LH-releasing
      hormone (LH-RH) vaccine in postmenopausal women. DESIGN: Pilot clinical study.
      SETTING: Normal human volunteers in a medical research-training environment.
      PATIENT(S): Three postmenopausal women with a mean age of 60 years, 5 years of
      amenorrhea, and severe hypoestrogenism with elevated serum LH and FSH.
      INTERVENTION(S): Intramuscular immunization with 300 micrograms LH-RH equivalent
      of the vaccine in two occasions 1 month apart. MAIN OUTCOME MEASURE(S): Patients
      were followed for clinical assessment and serum LH, FSH, and anti-LH-RH titers at
      regular monthly intervals for 7 months. RESULTS(S): The injection of the anti-LH
      RH vaccine followed by a booster injection 1 month later resulted in a sharp
      decrease, 60 days after the first injection, of both serum gonadotropins,
      accompanied by an increase in anti-LH-RH antibody titers, which were reversible
      after 180 days in the absence of further booster immunization. CONCLUSION(S):
      Active immunization offer a safe option to induce antibody response, which in the
      present regime employed was of about 6-months duration. This procedure opens new
      possibilities for its use as an affordable therapeutic agent in some hormone
      dependent clinical conditions.

PMID- 9022626
TI  - "The coming of wonders".

PMID- 9022627
TI  - What's new in cardiac surgery.

PMID- 9022628
TI  - What's new in colon and rectal surgery.

PMID- 9022630
TI  - What's new in endocrine surgery.

PMID- 9022629
TI  - What's new in critical care and metabolism.

PMID- 9022631
TI  - What's new in gastrointestinal surgery and hepatobiliary diseases.

PMID- 9022632
TI  - What's new in gynecologic and obstetrical surgery.

PMID- 9022633
TI  - What's new in neurosurgery.

PMID- 9022634
TI  - What's new in surgical oncology.

PMID- 9022635
TI  - What's new in ophthalmology.

PMID- 9022636
TI  - What's new in orthopaedic surgery.

PMID- 9022637
TI  - What's new in otolaryngology.

PMID- 9022638
TI  - What's new in pediatric surgery.

PMID- 9022639
TI  - What's new in plastic surgery.

PMID- 9022640
TI  - What's new in general thoracic surgery.

PMID- 9022641
TI  - What's new in transplantation.

PMID- 9022642
TI  - What's new in trauma and burns.

PMID- 9022643
TI  - What's new in urology.

PMID- 9022644
TI  - What's new in vascular surgery.

PMID- 9022645
TI  - Habitual, toxic, and lethal concentrations of 103 drugs of abuse in humans.
AB  - BACKGROUND: Poisoning caused by drugs of abuse or commonly used addictive
      medicines occurs with relative frequency and often leads, either directly or
      indirectly, to death. The interpretation of the blood and urine concentrations
      is, however, a complex and difficult problem. METHODS: We have reviewed the
      published data and subjected them to selection and unification on the basis of
      conservative criteria and our own experience. RESULTS: A compilation of the
      concentrations of 103 drugs of abuse in whole blood, serum/plasma, and urine,
      during habitual or therapeutic use and as found in toxic or lethal poisoning is
      given. CONCLUSIONS: The table presented can be helpful in interpretation of the
      drug concentrations encountered in clinical, toxicological, and forensic cases.

PMID- 9022646
TI  - Surveillance of loperamide ingestions: an analysis of 216 poison center reports.
AB  - BACKGROUND: Loperamide was approved for nonprescription use in 1988. While
      efficacy is well documented, there are few data on loperamide overdose and
      management. METHODS: Eight poison centers participated in a prospective study
      enrolling 216 patients. RESULTS: Where the amount ingested was known, it ranged
      from 0.03 to 0.94 mg/kg. One- to 3-year-olds were involved in 57.9% of
      ingestions. Ingestion was unintentional in 182 cases (84.3%), including 59
      patients with therapeutic errors (27.3% of all cases). Dispensing cup errors were
      implicated in 23 cases; 15 patients assumed the dispensing cup was the unit of
      measure. No symptoms developed in 63.0%; 27.8% had related symptoms. No related
      symptoms were life-threatening, and no fatalities occurred. The most frequent
      symptoms were drowsiness (15.7%), vomiting (4.2%), and abdominal pain or burning
      (3.7%). The frequency of related symptoms was compared in patients receiving the
      most frequently utilized decontamination modalities: ipecac alone, activated
      charcoal alone, lavage and activated charcoal, and ipecac and activated charcoal.
      Compared to the 112 patients who received no decontamination, only the ipecac
      treated group demonstrated a significant reduction in the frequency of related
      symptoms; 13.9% of patients given ipecac alone (without other gastric
      decontamination) had related symptoms compared to 33.0% of patients who received
      no decontamination. Three patients received naloxone for CNS symptoms related to
      loperamide; two responded and the response of the third was unknown. CONCLUSION:
      Within the range of doses implicated in this study (up to 0.94 mg/kg), there were
      no life threatening clinical effects and no fatalities. Development of a
      management protocol is complicated by the absence of a predictable clinical
      response in each dose range. The data suggest that children over six months with
      single acute ingestions up to 0.4 mg/kg, and possibly higher, can be safely
      managed at home, without gastric decontamination.

PMID- 9022647
TI  - Poison center data and the Pollyanna phenomenon.

PMID- 9022648
TI  - Carbamate poisoning in early childhood and in adults.
AB  - OBJECTIVE: Retrospective evaluation of the clinical course of carbamate poisoning
      in young children and adults. DESIGN: Thirty-six children aged 1 to 8 years
      (median 2.5 years) and 24 adults aged 17 to 41 years (median 22 years) ingested
      rat poison resulting in carbamate poisoning. The ingested poisons in all cases
      were positively identified as methomyl or aldicarb by gas chromatography-mass
      spectrometry. RESULTS: Symptoms of intoxication in children were compared to
      those in adults with similar depression of the serum cholinesterase. The
      predominant symptoms in young children were central nervous system depression and
      hypotonia. The most common muscarinic effect was diarrhea. In adults, the main
      signs were miosis and fasciculations. Fasciculations in children were less
      frequent. Central nervous system depression, hypotonia, and diarrhea were
      uncommon in adults. CONCLUSION: Based on a relatively large number of carbamate
      poisonings in young children, we conclude that the clinical presentation differs
      from adult poisoning manifestations. The absence of classic muscarinic effects
      does not exclude the possibility of carbamate poisoning in young children with
      central nervous system depression.

PMID- 9022649
TI  - Central and peripheral neurotoxic effects of chronic methyl bromide intoxication.
AB  - OBJECTIVE: To examine all methyl bromide poisonings reported to the Marseille
      Poison Centre and to describe more precisely the infrequent cases of chronic,
      nonacute exposure. DESIGN: Retrospective observational cohort. METHOD: Data
      retrieval from the French Poison Centres National Data Bank (ARIT) which contains
      all the cases of poisonings collected by the Marseille Poison Centre (Hot Line
      observations, Toxicovigilance, Toxicological intensive care unit). All methyl
      bromide poisonings 1973-1994 were examined to evaluate to frequency of the
      different circumstances. RESULTS: Of the 89 methyl bromide intoxications studied,
      there were two cases of chronic exposure: two workers presented with neurological
      signs of cerebello-vestibular and pyramidal deficits, visual troubles and
      peripheral neuropathy of the lower limbs at the end of a season of exposure
      during which no acute incident involved. In one patient, the symptoms improved
      within five months; in the other, paresthesia were still present two years later
      and were associated with visual after-effects. CONCLUSION: The incidence of
      chronic methyl bromide intoxication is low. The risk for chronic exposure or
      persistent toxic effects may be masked by the severity of the acute toxic
      effects. The development of peripheral neuropathy immediately after the central
      neurological signs was noted in our two subjects. A dying back axonopathy may
      explain this unique chronological evolution.

PMID- 9022650
TI  - Accidental intoxication with methylene dianiline p,p'-diaminodiphenylmethane:
      acute liver damage after presumed ecstasy consumption.
AB  - BACKGROUND: MDA is the abbreviation for methylene dianiline (p,p'
      diaminodiphenylmethane; 4,4'-methylenedianiline; CAS 101-77-9); and for
      methylendioxyamphetamine (MDMA, N, alpha-dimethyl-1,3-benzodioxole-5-ethanamine;
      CAS 42542-10-9). While the former is used for the production of polyurethane
      foams, the latter is a psychometric drug, which is becoming increasingly popular
      in the techno scene. METHODS: We report six participants of a technoparty (1
      female, 5 males, ages 17-25) who were admitted to the hospital with severe
      colicky abdominal pain and subsequently developed symptoms of hepatotoxicity.
      They had ingested an alcoholic beverage that had been spiked with a powdery
      substance they dubbed MDA. RESULTS: All patients showed similar clinical
      symptoms, with an identical time course. Acute jaundice developed within 2 days
      after ingestion. Enzymes indicating cholestasis increased steadily over 7 days
      and reached peak values of 800 U/L (AP) and 380 U/L (GGT), whereas transaminases
      remained moderately elevated. Between days 5 and 7, all patients became febrile
      for one day, their body temperatures rising up to 40 degrees C. There was no
      evidence for hemolysis or an infectious hepatitis. Toxicological analysis
      revealed the presence of p,p'-diaminodiphenylmethane (4,4'-methylenedianiline) at
      a concentration of 130 mg/L in one of two urine extracts examined. CONCLUSIONS:
      The analytical data indicate that the participants of the technoparty assumed the
      aniline-derivative, the cause of Epping Jaundice, was methylendioxyamphetamine
      because the same abbreviation, MDA, is used for both compounds. An overview of
      the acute liver toxicity of aniline derivatives is given and the possibility of
      amphetamine-induced liver damage is discussed.

PMID- 9022651
TI  - Experimental studies of methemoglobinemia due to percutaneous absorption of
      sodium nitrite.
AB  - OBJECTIVE: Methemoglobin formation caused by a liniment solution containing
      sodium nitrite (30 g/L and 140 g/L) was studied in rats with normal or abraded
      skin, by measuring the methemoglobin concentration before and after application
      of liniment solutions with differing nitrite concentration. METHODS: Each
      liniment solution (120 microL) was applied. Methemoglobin was measured for 180
      minutes using a hemoximeter. Simultaneously, arterial blood pressure and
      cutaneous blood flow was measured by laser Doppler flowmetry and a pressure
      transducer. RESULTS: After the application of each liniment solution to normal
      skin, the methemoglobin concentration was not significantly modified depending on
      the time after application. Application of liniment solution to abraded skin (140
      g/L) resulted in a marked increase in methemoglobin concentration. A remarkable
      decrease in arterial blood pressure and subcutaneous blood flow were observed
      after application of liniment solution to abraded skin (140 g/L). CONCLUSIONS:
      Each of these findings are characteristic of nitrite and they imply the
      percutaneous absorption of nitrite. Regardless of the nitrite concentration, the
      methemoglobin concentration was consistently higher in abraded skin than in
      normal skin.

PMID- 9022652
TI  - Brain mercury in neurodegenerative disorders.
AB  - BACKGROUND: Trace element neurotoxicity has long been invoked as an etiologic
      factor for Alzheimer's disease. This study was conducted to determine the
      concentrations of mercury in seven different brain regions from deceased patients
      histologically confirmed with Alzheimer's disease or multiple sclerosis as
      compared to control subjects without known central nervous system and renal
      disorders. Brain mercury concentrations in all deceased subjects can arise from
      amalgam restorations, diet, and the working environment. METHODS: Autopsy frozen
      specimens (control, Alzheimer's disease and multiple sclerosis) from seven brain
      regions, which included frontal cortex, temporal cortex, occipital cortex,
      putamen, hippocampus, corona radiata and corpus callosum were assayed for the
      concentrations of selenium using instrumental neutron activation analysis and
      mercury using radiochemical neutron activation analysis. RESULTS: We found that
      the concentrations of mercury and the mercury/selenium molar ratios were
      significantly lower in the hippocampi of multiple sclerosis patients as compared
      to aged-matched controls. However, no statistically significant differences were
      detected for the concentrations of mercury and the mercury/ selenium molar ratios
      for the remaining six brain regions among these groups. CONCLUSIONS: Since brain
      mercury concentrations from deceased subjects with either Alzheimer's disease or
      multiple sclerosis are not significantly higher than controls, the present study
      provides no scientific support that mercury plays a significant role in the
      pathogenesis of these neurologic disorders.

PMID- 9022653
TI  - Does concurrent acute ethanol ingestion during omeprazole therapy affect
      pituitary gonadal axis in male subjects?
AB  - OBJECTIVE: Literature suggests that both ethanol and omeprazole may affect the
      endocrine system. We studied the effect of concurrent use of ethanol and
      omeprazole on the pituitary gonadal axis in healthy males. METHODS: Serum
      testosterone, luteinizing hormone, and follicle stimulating hormone levels were
      assessed in a fasting state before and after ingestion of 0.5 g/kg bodyweight of
      ethanol. Subjects then received omeprazole therapy (20 mg 2x/d for one week)
      followed by assessment of hormone levels before and after ethanol ingestion as
      done previously. RESULTS: Total testosterone levels before and after ethanol at
      baseline declined an average of 46.6 ng/dL (n = 8; p = NS). The testosterone
      levels before and after ethanol following omeprazole therapy rose an average of
      55.4 ng/dL (n = 8; p = NS). There was no significant difference in the change of
      ethanol induced testosterone concentrations as a result of omeprazole therapy.
      Similarly the free testosterone, follicle stimulating hormone, and luteinizing
      hormone were also not affected by ethanol or omeprazole alone or in combination.
      CONCLUSIONS: We conclude that omeprazole and/or acute ingestion of ethanol do not
      affect the pituitary gonadal axis in healthy male subjects.

PMID- 9022654
TI  - Orellanine poisoning: rapid detection of the fungal toxin in renal biopsy
      material.
AB  - BACKGROUND: Mushroom poisoning by some species of the Cortinarius (Agaricales)
      often lead to irreversible renal failure caused by the nephrotoxin orellanine. In
      1994 and 1995, six poisoning outbreaks involving ten individuals in Northern
      Italy and in Austria were investigated. METHODS: A total of 87 clinical samples
      (urine and blood samples including renal biopsy material of three patients) were
      examined for the presence of orellanine by thin layer chromatography. RESULTS:
      Orellanine can be detected after a relatively long period following poisoning by
      performing a simple thin layer chromatography technique using small quantities of
      renal biopsy material. No toxin was found in urine or blood samples. CONCLUSIONS:
      Orellanine is rapidly concentrated in the kidneys in a relatively soluble form
      and cannot be detected in urine, blood and dialysis fluids at the time when first
      symptoms appear.

PMID- 9022655
TI  - Renal failure caused by mushroom poisoning.
AB  - BACKGROUND: In the Pacific Northwest region of the US and in southwestern British
      Columbia, Canada, isolated cases of renal failure have occurred following
      ingestion of wild mushrooms. We report four cases in which toxic mushrooms were
      mistaken for the edible pine mushroom or matsutake (Tricholoma magnivelare). CASE
      REPORTS: Gastrointestinal symptoms started five to eight hours after ingestion
      and continued for several days. Three of the four patients were found to be in
      renal failure when they presented to the emergency department 5-6 days post
      ingestion. One patient, an elderly diabetic, had renal dysfunction the day
      following ingestion. All patients received hemodialysis and supportive care and
      regained renal function. DISCUSSION: Symptoms and time of onset are similar to
      those reported in previous cases of Amanita smithiana poisoning. This suggests
      that the mushroom involved in these cases may also be Amanita smithiana which
      contains nephrotoxic compounds. In one of the cases, stem ends of the mushrooms
      were available for examination. Cellular elements conforming to those described
      as being present in the species Amanita smithiana were seen on light microscopy.
      CONCLUSION: Mushroom field guides warn against mistaking Amanita smithiana for
      pine mushrooms. They are similar in size, color and habitat. It appears possible
      that Amanita smithiana mushrooms were eaten instead of pine mushrooms in these
      cases.

PMID- 9022656
TI  - Evaluation of a colloidal metal immunoassay device for the detection of tricyclic
      antidepressants in urine.
AB  - BACKGROUND: The sensitivity and selectivity of a colloidal metal immunoassay
      device (Triage Plus TCA) which is designed for the rapid detection of tricyclic
      antidepressant drugs in urine at a total tricyclic antidepressant concentration
      of 1000 ng/mL or greater were evaluated. METHODS: The sensitivity of the Triage
      Plus assay was determined by adding known amounts of amitriptyline,
      nortriptyline, imipramine, desipramine, doxepin and desmethyl-doxepin to drug
      free urine. The selectivity of the assay was determined by adding known
      concentrations of 32 drugs or drug metabolites commonly encountered in emergency
      department admissions to drug free urine. Triage Plus results from clinical urine
      specimens containing either amitriptyline, nortriptyline, imipramine,
      desipramine, doxepin and desmethyl-doxepin were compared to those obtained with
      thin layer chromatography and high performance liquid chromatography. RESULTS:
      Triage Plus yielded a positive response to gravimetrically prepared urines of
      tricyclic antidepressant at the stated cut-off value (1,000 ng/mL), and at 80%
      (800 ng/mL) and 50% (500 ng/mL) of the cut-off with amitriptyline, nortriptyline,
      imipramine, desipramine and doxepin. Other tricyclic antidepressant drugs,
      clomipramine and protriptyline were positive at 1000 ng/mL. Significant cross
      reactivity was observed only with cyclobenzaprine at 1000 ng/mL. No significant
      cross reactivity was found at 1.0 g/L for 32 drugs commonly encountered in
      emergency department admissions. A 95% (70/74) agreement of positive tricyclic
      antidepressant results was observed between Triage Plus and thin layer
      chromatography. Discordant urines were found by high performance liquid
      chromatography to contain tricyclic antidepressant concentrations below the cut
      off value of the colloidal metal assay. CONCLUSION: Triage Plus was found to be
      an accurate device for the detection of tricyclic antidepressants in urine at the
      stated cut-off value of 1000 ng/mL tricyclic antidepressant. With the exception
      of cyclobenzaprine, significant cross-reactivity was not observed with other
      drugs commonly encountered in emergency department admissions.

PMID- 9022657
TI  - Intravenous self-administration of metallic mercury: report of a case with a 5
      year follow-up.
AB  - CASE REPORT: A case of intravenous self-administration of elementary mercury is
      presented. The increase urinary excretion of mercury after treatment with 2,3
      dimercaptopropane-1-sulfonate is reported on a 5-year follow-up. No biochemical
      abnormalities in hepatic or renal function nor clinical pulmonary malfunction
      have been detected, despite the persistence of metallic densities in the body.
      The only persistent symptoms are tremor and lower extremity weakness. Any long
      term benefits of 2,3-dimercaptopropane-1-sulfonate treatment remains to be
      determined.

PMID- 9022658
TI  - Effect of charcoal hemoperfusion on clearance of pentamidine isethionate after
      accidental overdose.
AB  - BACKGROUND: Pentamidine isethionate is an antimicrobial agent effective in the
      treatment of Pneumocystis carinii pneumonia, trypanosomiasis and leishmaniasis.
      Severe and fatal toxicity is reported with pentamidine use. CASE REPORT: A
      patient received an accidental overdose (40 times the prescribed dose) of
      intravenous pentamidine due to a pharmacy mixing error. Charcoal hemoperfusion
      was utilized to attempt to lower the serum concentration of pentamidine and
      lessen toxicity. RESULTS: Measurement of pentamidine concentrations in the
      patient's blood demonstrates a beneficial effect of hemoperfusion. CONCLUSIONS:
      Charcoal hemoperfusion may represent a useful modality in the management of
      pentamidine isethionate overdosage.

PMID- 9022659
TI  - Syndrome of inappropriate secretion of antidiuretic hormone in two elderly women
      with elevated serum fluoxetine.
AB  - OBJECTIVE: Fluoxetine is widely prescribed for depressed patients. Hyponatremia
      secondary to inappropriate secretion of antidiuretic hormone has been reported in
      a few cases associated with routine use of fluoxetine, especially in elderly
      patients. The mechanism has been postulated to be linked to the inappropriate
      secretion of antidiuretic hormone. Serum concentrations of antidiuretic hormone
      and fluoxetine have not been reported in previously published reports. CASE
      REPORT: We report two new cases of severe and reversible hyponatremia associated
      with routine use of fluoxetine therapy in two elderly women. Fluoxetine-induced
      inappropriate secretion of antidiuretic hormone was confirmed by elevated serum
      concentrations of antidiuretic hormone and fluoxetine.

PMID- 9022660
TI  - Treatment of severe thallium intoxication.
AB  - CASE REPORT: We report a successfully treated case of severe thallium
      intoxication. In spite of very high serum thallium (5,240 micrograms/L),
      symptomatology was minor and recovery complete. Prussian Blue was administered,
      diuresis was enhanced by intravenous fluids and a prolonged hemodialysis was
      started early. High blood flows (300 mL/min) and intravenous potassium chloride
      supplements, to mobilize thallium from the tissues, resulted in good clearances
      (96 to 150 mL/min). In order to prevent the well known complications, we
      recommend aggressive treatment of severe thallium intoxication.

PMID- 9022661
TI  - Exfoliative dermatitis associated with diltiazem.
AB  - BACKGROUND: Exfoliative dermatitis due to calcium channel blockers is a known but
      infrequent response. CASE REPORT: A 77-year-old woman began treatment with
      diltiazem for angina pectoris. Three days later, severe exfoliative dermatitis
      developed. CONCLUSION: The present case and the others previously reported
      emphasize the need for greater awareness of the occurrence of adverse cutaneous
      reactions including toxic epidermal necrolysis, Stevens-Johnson syndrome and
      cutaneous vasculitis due to calcium channel blockers including diltiazem.

PMID- 9022662
TI  - Pemoline induced acute choreoathetosis: case report and review of the literature.
AB  - BACKGROUND: Pemoline is an oxazolidine derivative that is structurally different
      from amphetamines and used in the treatment of attention deficit disorder.
      Pemoline has not been commonly associated in the literature as a cause of acute
      movement disorders. The following case describes two children acutely poisoned
      with pemoline who experienced profound choreoathetosis. CASE REPORT: Two, 3-year
      old male, identical twin siblings presented to the emergency department after
      found playing with a an empty bottle of pemoline originally containing 59
      tablets. The children had a medical history significant for attention deficit
      disorder previously treated with methylphenidate without success. This was their
      first day of pemoline therapy. The choreoathetoid movements began 45 min to 1 h
      after ingestion. The children gave no history of prior movement disorders and
      there was no family history of movement disorders. The children received
      gastrointestinal decontamination and high doses of intravenous benzodiazepines in
      an attempt to control the choreoathetoid movements. Despite treatment, the
      children continued to have choreoathetosis for approximately 24 hours. Forty
      eight hours after admission, the children appeared to be at their baseline and
      were discharged home. CONCLUSION: Pemoline associated movement disorder has been
      rarely reported in the acute toxicology literature. The possibility of
      choreoathetoid movements should be considered in patients presenting after
      pemoline overdose.

PMID- 9022663
TI  - Toxic inhalation of ethylene glycol: a pharmacological improbability.

PMID- 9022664
TI  - Alpha-interferon induced severe pneumonitis.

PMID- 9022665
TI  - Sulfonylurea ingestions: hospitalization not mandatory.

PMID- 9022667
TI  - Structure and transcriptional regulation of human alpha-mannosidase IIX (alpha
      mannosidase II isotype) gene.
AB  - Golgi alpha-mannosidase II is a key enzyme of N-glycan processing. Its genetic
      defect is associated with HEMPAS (hereditary erythroblastic multinuclearity with
      positive acidified serum lysis test). We previously cloned cDNAs of human alpha
      mannosidase II (alpha-MII) and its isotype, alpha-mannosidase IIX [alpha-MIIX,
      Misago, M., Liao, Y. F., Eto, S., Mattei. M. G., Moremen. K. W. & Fukuda, M. N.
      (1995) Proc. Natl Acad. Sci. USA 92, 11766-11770]. Constitutive expressions of
      alpha-MII and alpha-MIIX mRNA were shown in various human tissues. To investigate
      the transcriptional regulation of alpha-MIIX gene, we characterized the cosmid
      clone of 40-kb that includes the 5'-flanking sequence. This clone contains at
      least eight exons which encode 396 amino acid residues of a total of 1139 amino
      acid residues of alpha-MIIX. Primer-extension analysis revealed multiple
      transcription-initiation sites in the range from -70 to -58 relative to the
      translation-initiation site. No canonical TATA or CAAT boxes were observed, but a
      (G + C)-rich region was found in close proximity to the transcription-initiation
      site. To localize the transcriptional regulatory region of this gene, various
      regions of the 5' sequences were fused to the luciferase gene, and transient
      expression assays were conducted in human melanoma G-361 cells. These studies
      indicated that sequence from -12 to + 11 relative to the most distal 5'
      transcription-initiation site was involved in the promoter function. Within this
      region, the sequence GGGCGT similar to the consensus sequence of the Sp1 binding
      site, is present at positions -12 to -7. Enhancer activities were found in the
      region upstream of this site, notably from -4300 to -252. Thus, the alpha-MIIX
      promoter located in a CpG island is also regulated by upstream elements,
      indicating the complexity of alpha-MIIX gene expression.

PMID- 9022666
TI  - Pancreatic development and maturation of the islet B cell. Studies of pluripotent
      islet cultures.
AB  - Pancreas organogenesis is a highly regulated process, in which two anlage
      evaginate from the primitive gut. They later fuse, and, under the influence of
      the surrounding mesenchyme, the mature organ develops, being mainly composed of
      ductal, exocrine and endocrine compartments. Early buds are characterized by a
      branching morphogenesis of the ductal epithelium from which endocrine and
      exocrine precursor cells bud to eventually form the two other compartments. The
      three compartments are thought to be of common endodermal origin; in contrast to
      earlier hypotheses, which suggested that the endocrine compartment was of
      neuroectodermal origin. It is thus generally believed that the pancreatic
      endocrine-lineage possesses the ability to mature along a differentiation pathway
      that shares many characteristics with those of neuronal differentiation. During
      recent years, studies of insulin-gene regulation and, in particular, the tissue
      specific transcriptional control of insulin-gene activity have provided
      information on pancreas development in general. The present review summarizes
      these findings, with a special focus on our own studies on pluripotent endocrine
      cultures of rat pancreas.

PMID- 9022668
TI  - Substrate specificity and inhibitor sensitivity of Ca2+/S100-dependent twitchin
      kinases.
AB  - Myosin-associated giant protein kinases of the titin/witchin-like superfamily
      have previously been implicated in the regulation of muscle function, based on
      genetic and physiological studies. We find that recombinant constitutively active
      Caenorhabditis elegans and Aplysia twitchin kinase fragments differ in their
      catalytic activities and peptide-substrate specificities, as well as in their
      sensitivities to the naphthalene sulfonamide inhibitors 1-(5
      chloronaphthalenesulfonyl)-1H-hexahydro-1,4-diazepine (ML-7) and 1-(5
      iodonaphthalenesulfonyl)-1H-hexahydro-1,4-diazepine (ML-9). The constitutively
      active Aplysia twitchin kinase fragment has a remarkably high activity (Vmax >
      100 mumol.min-1.mg-1) towards some substrate peptides. The autoinhibited forms of
      these twitchin kinases can be activated in a Ca(2+)-dependent manner by the
      dimeric form of the S100A1 protein (S100A1(2)). The twitchin kinase S100A1(2)
      binding site can also bind Ca2+/calmodulin but neither kinase is activated by
      calmodulin. The data provide a functional basis for the ongoing crystallographic
      study of twitchin kinase fragments.

PMID- 9022669
TI  - Molecular cloning and characterization of a transcription factor for the C-type
      natriuretic peptide gene promoter.
AB  - Our previous studies on the promoter function of the human C-type natriuretic
      peptide (CNP) gene revealed the existence of two GC-rich cis elements essential
      for gene transcription in rat pituitary-derived GH3 cells. To isolate
      transcription factors that bind to those GC-rich elements, we screened a lambda
      ZAP cDNA library derived from GH3 cells by Southwestern screening. Several
      positive clones with specific binding abilities were obtained, and one was
      identical as TSC-22, a speculated transcriptional modulator stimulated by
      transforming growth factor beta (TGF-beta) of unknown function. TSC-22
      significantly enhanced CNP promoter activity in GH3 cells. We further cloned a
      1.8-kb full-length human TSC-22 cDNA from a fetal kidney cDNA library by a
      combination of polymerase chain reaction and the rapid amplification of the cDNA
      ends technique. In adults, human TSC-22 mRNA was highly expressed in brain, lung
      and heart. TSC-22 gene expression in GH3 and human aortic endothelial cells was
      stimulated by cytokines including TGF-beta, in correlation with the CNP mRNA
      increase. These results suggest that TSC-22 is a transcriptional regulator of the
      CNP gene and transmits signals from cytokines, such as TGF-beta, to CNP gene
      expression.

PMID- 9022670
TI  - Pituitary adenylate-cyclase-activating polypeptide stimulates proto-oncogene
      expression and activates the AP-1 (c-Fos/c-Jun) transcription factor in AR4-2J
      pancreatic carcinoma cells.
AB  - Pituitary adenylate-cyclase-activating polypeptide (PACAP) has been shown to
      possess mitogenic activity in various tumor cells. The present study was designed
      to investigate signal transduction mechanisms and expression of the proto
      oncogenes c-fos and c-jun linked to the mitogenic effect of PACAP in the
      pancreatic carcinoma cell line AR4-2J. PACAP-(1-27)-peptide and PACAP-(1-38)
      peptide, but not the structurally related vasoactive intestinal polypeptide
      (VIP), potently stimulated [3H]thymidine incorporation and cell number at doses
      of 0.1-10 nM. Both molecular forms of PACAP strongly increased formation of cAMP
      and inositol trisphosphate, elevated cytosolic Ca2+ levels and induced mitogen
      activated protein (MAP) kinase activity. Quantitative reverse-transcription PCR
      revealed that PACAP-(1-27)-peptide and PACAP-(1-38)-peptide elevated c-fos mRNA
      levels 50-100-fold, whereas c-jun mRNA levels increased only moderately (2-3
      fold). The effect of PACAP on c-fos and c-jun expression in AR4-2J cells was
      rapid (20 min), transient (1-2 h), dose-dependent IC50, 0.5 nM) and was abolished
      by the specific PACAP receptor antagonist PACAP-(6-38)-peptide or inhibitors of
      protein kinase C or tyrosine kinases. Compared with PACAP, epidermal growth
      factor and gastrin equipotently stimulated c-fos transcription whereas VIP,
      secretin, forskolin or phorbolester showed only marginal effects. Both PACAP (1
      27)-peptide and PACAP-(1-38)-peptide strongly increased the DNA binding activity
      of the c-fos/ c-jun heterodimer transcription factor AP-1 at 10 nM and also
      stimulated AP-1 transcriptional activity up to 20-fold in AR4-2J cells. These
      findings indicate that the mitogenic effect of PACAP mediated via activation of
      the GTP-binding protein coupled PACAP/VIP-1 (PV1) receptor is linked to the MAP
      kinase cascade, increased expression of the proto-oncogenes c-fos and c-jun and
      activation of the heterodimeric transcription factor AP-1.

PMID- 9022671
TI  - Molecular basis of residue 192 participation in determination of coagulation
      protease specificity.
AB  - Residue 192 (chymotrypsin numbering system) in thrombin, activated protein C, and
      factor Xa contributes to the specificity of these enzymes toward their substrates
      and inhibitors. A Glu192-->Gln mutation in both thrombin and activated protein C
      yielded enzymes that reacted better with some, but not all, of their natural
      substrates and inhibitors. To determine whether the specificity change is due to
      productive interactions of Gln192 with substrates and inhibitors or elimination
      of repulsive electrostatic interactions, we prepared forms of thrombin, des-(1
      45)-factor Xa and activated des-(1-45)-protein C with Glu, Gln, or Met at
      position 192 and compared their activities toward inhibitors and substrates. All
      mutants had nearly normal amidolytic activity. The Glu192-->Gln and Glu 192-->Met
      mutations of thrombin and activated des-(1-45)-protein C increased the second
      order rate constant (k2) of inhibition by alpha 1-antitrypsin about 700-fold and
      170-fold for thrombin, and 185-fold and 150-fold for activated des-(1-45)-protein
      C, respectively. [E192]faxtor Xa, but not [M192]factor Xa, was resistant to
      inhibition by alpha 1-antitrypsin. Glu-->Gln or Glu-->Met mutants of both
      thrombin and activated des-(1-45)-protein C were effectively inhibited by tissue
      factor pathway inhibitor (K1 < 200 nM) and, except for [M192]thrombin, by bovine
      pancreatic trypsin inhibitor (K1 < 60 nM). With respect to substrate cleavage,
      Glu192-->Gln and Glu192-->Met mutations of activated des-(1-45)-protein C both
      inactivated factor Va 2-3-fold faster than activated des-(1-45)-protein C.
      Thrombin and [M192]thrombin activated protein C at similar slow rates compared to
      rapid activation by [Q192]thrombin. The Gln192-->Met mutants of des-(1-45)-factor
      Xa activated prethrombin 1.8-11-fold slower than wild-type enzyme. With
      thrombomodulin or factor Va present, these differences in protein C and
      prethrombin 1 activation rates were decreased to about 2-fold. We conclude that
      residue 192 contribution to enzyme specificity is achieved by both productive and
      repulsive interactions and that the magnitude and nature of the participation
      varies among enzymes, substrates and inhibitors.

PMID- 9022672
TI  - Intermolecular and intramolecular interactions of the 33-kDa protein in
      photosystem II.
AB  - Intermolecular and intramolecular interactions of the extrinsic 33-kDa protein in
      photosystem II were investigated by cross-linking with a water-soluble
      carbodiimide as cross-linking agent. This zero-length cross-linker is known to
      cross-link the 33-kDa protein to the chlorophyll-alpha-binding protein CP47
      [Bricker, T. M., Odom, W. R. & Queirolo, C. B. (1988) FEBS Lett. 231, 111-117;
      Enami, I., Kaneko, M., Kitamura, N., Koike, H., Sonoike, K., Inoue, Y & Katoh, S.
      (1991) Biochim. Biophys. Acta 1960, 224-232]. In this work, cross-linking was
      observed not only to CP47 but also to a small intrinsic subunit. In addition,
      through the use of a high-resolution SDS-gel system, three intramolecular cross
      linked products of the 33-kDa protein were detected. To search for additional
      cross-linking sites that might not be accessible to the cross-linker in intact
      photosystem II, the isolated 33-kDa protein was activated for cross-linking and
      subsequently bound to CaCl2-washed photosystem II. In the complementary
      experiment, CaCl2-washed photosystem II was activated, then reconstituted with
      the 33-kDa protein. The results of the cross-linking reactions demonstrated that
      all carboxylic acid groups involved in cross-linking were located on the 33-kDa
      protein and all primary amines were located on intrinsic membrane proteins. No
      cross-linking other than those observed in cross-linking experiments with intact
      photosystem II were observed. This indicated that the 33-kDa protein is bound to
      CP47 and a small subunit but not to the photosystem II reaction centre. This
      observation is consistent with the finding that cross-linking was independent of
      the presence or absence of the manganese cluster. Possible residues on the 33-kDa
      protein and CP47 involved in cross-linking are suggested.

PMID- 9022674
TI  - Primary structures of fungal fructosyl amino acid oxidases and their application
      to the measurement of glycated proteins.
AB  - Fructosyl amino acid oxidase (FAOD), which is active toward model compounds of
      the glycated proteins in blood, N epsilon-fructosyl N sigma-Z-lysine and N
      fructosyl valine, was purified to homogeneity from Aspergillus terreus GP1.
      Though the enzyme did not use glycated proteins directly as its substrate, it
      used glycated human serum albumin (HSA) when HSA was treated with a protease.
      Linear relationships between both the concentration and the increase in
      absorbance and the glycation rate of glycated HSA and the increase in absorbance
      were observed. cDNAs coding for FAODs were cloned from cDNA libraries of A.
      terreus GP1 and Penicillium janthinellum AKU 3413. The coding region for both
      fungal FAODs consisted of 1314 bp encoding 437 amino acids. The sequence of a
      dinucleotide-binding motif, GXGXXG, was in the deduced N-terminal region and a
      similar sequence to that the active site of bacterial sarcosine oxidases was
      found near the C-terminal region of FAOD. The of C-terminal tripeptides SKL and
      AKL of FAODs from A. terreus and P. janthinellum, respectively, represent typical
      peroxisomal-targeting signals. Finally, FAOD protein was produced in Escherichia
      coli transformants in an active form, and at the same level as in the original
      fungi.

PMID- 9022673
TI  - Chemical synthesis and characterization of maurotoxin, a short scorpion toxin
      with four disulfide bridges that acts on K+ channels.
AB  - Maurotoxin is a toxin isolated from the venom of the Tunisian chactoid scorpion
      Scorpio maurus. It is a 34-amino-acid peptide cross-linked by four disulfide
      bridges. Maurotoxin competes with radiolabeled apamin and kaliotoxin for binding
      to rat-brain synaptosomes. Due to its very low concentration in venom (0.6% of
      the proteins), maurotoxin was chemically synthesized by means of an optimized
      solid-phase technique. The synthetic maurotoxin was characterized. It was lethal
      to mice following intracerebroventricular injection (LD50, 80 ng/mouse). The
      synthetic maurotoxin competed with 125I-apamin and 125I-kaliotoxin for binding to
      rat-brain synaptosomes with half-maximal effects at concentrations of 5 nM and
      0.2 nM, respectively. Synthetic maurotoxin was tested on K+ channels and was
      found to block the Kv1.1, Kv1.2, and Kv1.3 currents with half-maximal blockage
      (IC50) at 37, 0.8 and 150 nM, respectively. Thus, maurotoxin is a scorpion toxin
      with four disulfide bridges that acts on K+ channels. The half-cystine pairings
      of synthetic maurotoxin were identified by enzymatic cleavage. The pairings were
      Cys3-Cys24, Cys9-Cys29, Cys13-Cys19 and Cys31-Cys34. This disulfide organization
      is unique among known scorpion toxins. The physicochemical and pharmacological
      properties of synthetic maurotoxin were indistinguishable from those of natural
      maurotoxin, which suggests that natural maurotoxin adopts the same half-cystine
      pairing pattern. The conformation of synthetic maurotoxin was investigated by
      means of circular dichroism spectroscopy and molecular modeling. In spite of its
      unusual half-cystine pairings, the synthetic-maurotoxin conformation appears to
      be similar to that of other short scorpion toxins.

PMID- 9022675
TI  - In vivo modulation of annexins I, II and V expression by thyroxine and
      methylthiouracil.
AB  - Regulation of annexin concentration and localization were investigated in thyroid
      tissues of hypothyroid [methylthiouracil (MeSur) treatment], euthyroid (control)
      and hyperthyroid [thyroxine (T4) treatment] rats. A low level of circulating
      thyroid hormones induces a decrease of total thyroid calcium-binding protein
      concentration when compared with the concentration in unstimulated animals.
      Conversely, concentrations of annexins I, II and V increase. The accumulation of
      these proteins in two subcellular compartments (cytosolic and particulate
      fractions) can be reversed by addition of thyroid hormones. The finding of a
      specific increase in annexins concentration in thyroid-hormone-deficient rats,
      with a general decrease of the total calcium-binding protein content points to a
      very important role of these proteins in the cells. Furthermore, hyperthyroidisnt
      gives opposite results. To investigate the transduction pathway of annexins I-,
      II- and V-induced biosynthesis by thyroid hormones in thyroid glands, we used
      cultured pig thyroid cells as in vitro model system. In previous work [16], we
      have shown that annexin concentrations and localization are under TSH control via
      the adenylate cyclase pathway. In the presence of MeSur (in the culture medium),
      the protein-binding iodine remains low, indicative of weak thyroid hormone
      synthesis (data not shown) and that the annexins content is unchanged. These
      results suggest that, in thyroid tissue, an indirect mechanism links thyroid
      hormones to annexin expressions via the TSH feed-back loop, and excludes
      autocrine regulation.

PMID- 9022676
TI  - Expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor
      nuclear translocator (Arnt) in adult rabbits known to be non-responsive to
      cytochrome P-450 1A1 (CYP1A1) inducers.
AB  - Induction of aryl hydrocarbon hydroxylase by aryl hydrocarbons occurs only in
      neonatal rabbits and not in adult rabbits [Kahl, G. F., Friederich, D. E.,
      Bigelow, S. W., Okey, A. B. & Nebert, D. W. (1980) Dev. Pharmacol. Ther. 1,137
      162]. In the present study, we isolated cDNA clones encoding aryl hydrocarbon
      receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) from
      adult rabbits. The deduced amino acid sequences of rabbit AhR and Arnt showed 80%
      and 94% identities with those of human AhR and Arnt, respectively. Rabbit AhR
      mRNA was predominantly expressed in the lung and liver. In contrast, rabbit Arnt
      mRNA was expressed at almost the same level in all tissues except for the heart,
      liver, and small intestine. Gel shift analysis showed that the AhR. Arnt complex
      could bind to the consensus xenobiotic-responsive element, which indicates that
      AhR expressed in adult rabbit liyers possessed binding activity to the consensus
      xenobiotic-responsive element in vitro, although aryl hydrocarbons did not induce
      the activity of AHH in adult rabbits. We propose that the incapability of adult
      rabbits to induce cytochrome P-450 1A1 (CYP1A1) is caused by factors other than
      AhR and Arnt.

PMID- 9022677
TI  - The recombinant alpha isoform of protein kinase CK1 from Xenopus laevis can
      phosphorylate tyrosine in synthetic substrates.
AB  - The cDNA coding for protein kinase CK1 alpha has been cloned from a Xenopus
      laevis cDNA library. The derived amino acid sequence of the protein contains 337
      amino acids and has a calculated molecular mass of 38874 Da. The sequence is
      identical to that of the human CK1 alpha and to the bovine CK1 alpha, except that
      it is 12 amino acids longer than the latter protein. Southern blotting with a 264
      bp probe demonstrates that four or more fragments are obtained upon digestion of
      genomic DNA with EcoR1 and Hind3, suggesting that X. laevis possesses a family of
      related CK1 genes. CK1 alpha was expressed in Escherichia coli as a glutathione
      transferase fusion protein (GT-CK1 alpha) and certain of its characteristics were
      determined. The recombinant GT-CK1 alpha fusion protein was found to have
      apparent Km values for ATP (12 microM), casein (1.5 mg/ml) and the specific
      peptide substrate RRKDLHDDEEDEAMSITA (180 microM) which are similar to those of
      the rat liver CK1 enzyme. The recombinant CK1 alpha activity is weakly inhibited
      by heparin, but strongly inhibited by poly(Glu80:Tyr20). This inhibition is
      competitive and shows an approximate K1 of 5 microM. CK1 alpha can phosphorylate
      the tyrosine residues of poly(Glu80:Tyr20) and the tyrosine residue in the
      synthetic peptide RRREEEYEEEE. This kinase preparation also autophosphorylates in
      serine, threonine and weakly in tyrosine.

PMID- 9022678
TI  - Activation of signaling pathways in HL60 cells and human neutrophils by
      farnesylthiosalicylate.
AB  - Effects of the farnesylcysteine mimetic, farnesylthiosalicylate on the activation
      of myeloid cells were studied. In dimethyl-sulfoxide-differentiated HL60 cells
      and in human neutrophils farnesylthiosalicylate (< or = 20 microM) dose
      dependently elevated cytosolic Ca2+ concentrations, suggesting phospholipase-C
      mediated release of the ion from intracellular stores. In human neutrophils, in
      addition to the production of inositol trisphosphate, farnesylthiosalicylate
      induced activation of the NADPH oxidase and translocation of the cytosolic
      oxidase components p47-phox and p67-phox to the membrane. The calcium signal,
      inositol-trisphosphate production and superoxide generation elicited by
      farnesylthiosalicylate were partially blocked by treatment of the cells with
      pertussis toxin, consistent with participation of pertussis-toxin-sensitive and
      pertussis-toxin-resistant elements. In HL60 cells, farnesylthiosalicylate (< or =
      20 microM) did not activate NADPH oxidase but dose-dependently augmented PMA
      elicited activity of the enzyme. This effect was resistant to pertussis-toxin
      treatment. In vitro augmentation of PKC-mediated phosphorylation of histone and
      cytosolic p47-phox by farnesylthiosalicylate and the finding that downregulation
      of PKC abrogated potentiation of NADPH oxidase activity by farnesylthiosalicylate
      were compatible with the involvement of PKC in the response of HL60 cells to
      farnesylthiosalicylate. It is suggested that the effects of
      farnesylthiosalicylate on myeloid cells reflect interaction of the analog with
      prenylcysteine-docking sites on cellular signaling elements.

PMID- 9022679
TI  - Glutamine inhibits the lowering effect of glucose on the level of
      phosphoenolpyruvate carboxykinase mRNA in isolated rat hepatocytes.
AB  - The expression of phosphoenolpyruvate carboxykinase (P-pyruvate CK) was shown to
      be decreased by hypoosmolarity and increased by glutamine in perfused liver from
      fed rats [Newsome, W. P., Warskulat, U., Noe, B., Wettstein, M., Stoll, B.,
      Gerok, W. & Haussinger, D. (1994) Biochem, J. 304, 555-560]. This work was
      undertaken to specify the mechanisms of glutamine action, using isolated
      hepatocytes from rats that had been starved for 24 h. At low concentrations (up
      to 5 mM), glutamine elicited a decrease in the level of P-pyruvate CK mRNA
      through cell swelling and, at higher concentrations, an increase in the mRNA
      level was observed. Experiments with combinations of glucose and glutamine or
      glucose and various amino acids demonstrated that glutamine counteracted the
      inhibitory effect of glucose on P-pyruvate CK mRNA at a transcriptional, level,
      and strongly suggested that the amide group of glutamine was involved in this
      effect. The metabolism of glucose was required for the reinforcement of the
      apparent stimulatory effect of glutamine, as demonstrated by the use of various
      sugars. Glucosamine, but not mannosamine, increased the level of P-pyruvate CK
      mRNA, as did glucose plus glutamine. These results suggest that the pathway
      leading from glucosamine-6-phosphate production might be responsible, at least
      partly, for the effect observed on P-pyruvate CK mRNA.

PMID- 9022680
TI  - Interleukin-1 beta induces nuclear factor kappa B in epithelial cells
      independently of the production of reactive oxygen intermediates.
AB  - A large body of work has been devoted to tumor necrosis factor alpha or
      interleukin-1 beta (IL-1 beta) signaling leading to the activation of the
      transcription factor nuclear factor-kappa B (NF-kappa B) in various cell types.
      Several studies have indicated that NF-kappa B activation depends strictly on the
      production of reactive oxygen intermediates. In this report, we first
      demonstrated that IL-1 beta is a potent activator of NF-kappa B in various
      epithelial transformed cell lines (OVCAR-3, SKOV-3, MCF7 A/Z). In these cells, IL
      1 beta rapidly induces NF-kappa B through a complete degradation of I kappa B
      alpha, while H2O2 activates NF-kappa B with slower kinetics through a partial
      degradation of I kappa B-alpha, p100 and p105. We showed that IL-1 beta-mediated
      induction of NF-kappa B in OVCAR-3 and in other epithelial cell lines does not
      proceed through the production of reactive oxygen intermediates, while the same
      cytokine activates NF-kappa B in lymphoid cells through the intracellular
      generation of H2O2. Our study demonstrated that several signaling pathways lead
      to the activation of NF-kappa B, following IL-1 beta treatment in different cell
      types.

PMID- 9022681
TI  - Identification of differentially expressed genes during hepatocytes development
      and characterization of their prenatal hormonal induction.
AB  - Upon birth, the liver acquires new functions as a result of the initiation of
      expression of key enzymes. One example is the initiation of gluconeogenesis which
      depends on the induced appearance of phosphoenolpyruvate carboxykinase (P
      pyruvate-CK) at birth. To characterize other genes that undergo such regulation,
      a differential screening was performed on a cDNA library from well-differentiated
      hepatoma cells. The pattern of tissue-specific and developmental-specific
      expression was determined for seven genes. Three clones, out of which two encode
      for the known genes alcohol dehydrogenase class I (ADH) and phenylalanine 4
      monooxygenase (PAH) and a new gene (clone 116-3), exhibited a pattern of
      expression similar to that of the P-pyruvate-CK gene, i.e. their expression was
      liver and kidney specific and induced in the liver upon birth. Determination of
      the sequence of clone 116-3 revealed that it belonged to the UDP
      glucuronosyltransferases type 2 (UGT2) family and thus was named UGT2B-rH4. To
      examine whether expression of the various genes could be prematurely induced by
      hormones in the fetal liver, either high levels of cAMP or low levels of insulin
      were induced in utero. The results demonstrated that cAMP induced a marked
      expression only of the genes for P-pyruvate-CK and ADH but not of those for PAH
      or UGT2B-rH4, while insulin deficiency induced premature expression of all four
      genes. We suggest that a set of genes whose expression is specifically induced in
      the liver upon birth can be prematurely induced by the hormones in utero.

PMID- 9022682
TI  - Studies on the biosynthesis of ovothiol A. Identification of 4-mercaptohistidine
      as an intermediate.
AB  - The recent discovery of N1-methyl-4-mercaptohistidine (ovothiol A), a small
      aromatic thiol, in Crithidia fasciculata made it possible to study its
      biosynthesis in an organism which can be cultured in large quantities and under
      defined growth conditions. Radiolabeling experiments using intact cells indicated
      that the methyl group in ovothiol A is derived from methionine, while 35S was
      incorporated from either cysteine or methionine. Three lines of evidence
      suggested that transsulfuration preceded the methylation step: (a) Crithidia
      fasciculata failed to convert radiolabeled N pi-methylhistidine to ovothiol A.
      (b) Ovothiol A was poorly separated from a component which was labeled by
      [14C]histidine and by [35S]cysteine, but not by [methyl-3H] methionine. (c)
      Dialysed crude extracts of C. fasciculata catalysed the conversion of histidine
      to a thiolated species in the presence of pyridoxal phosphate, iron and cysteine
      in the absence of S-adenosylmethionine. The product of the in vitro reaction was
      isolated as the bimane derivative. Structural analysis using 1H and 13C-NMR
      spectroscopy confirmed its identity as the bimane derivative of 4
      mercaptohistidine.

PMID- 9022683
TI  - NMR studies of the Escherichia coli Trp repressor.trpRs operator complex.
AB  - To understand the specificity of the Escherichia coli Trp repressor for its
      operators, we have begun to study complexes of the protein with alternative DNA
      sequences, using 1H-NMR spectroscopy. We report here the 1H-NMR chemical shifts
      of a 20-bp oligodeoxynucleotide containing the sequence of a symmetrised form of
      the trpR operator in the presence and absence of the holorepressor. Deuterated
      protein was used to assign the spectrum of the oligodeoxynucleotide in a 37-kDa
      complex with the Trp holorepressor. Many of the resonances of the DNA shift on
      binding to the protein, which suggests changes in conformation throughout the
      sequence. The largest changes in shifts for the aromatic protons in the major
      groove are for A15 and G16, which are thought to hydrogen bond to the protein,
      possibly via water molecules. We have also examined the effect of DNA binding on
      the corepressor, tryptophan, in this complex. The indole proton resonance of the
      tryptophan undergoes a downfield shift of 1.2 ppm upon binding of DNA. This large
      shift is consistent with hydrogen bonding of the tryptophan to the phosphate
      backbone of the trpR operator DNA, as in the crystal structure of the holoprotein
      with the trp operator.

PMID- 9022684
TI  - Biosynthesis and processing of type XVI collagen in human fibroblasts and smooth
      muscle cells.
AB  - The alpha 1(XVI) collagen chain, recently identified by cDNA cloning, exhibits
      structural similarity to a subgroup of collagens that associate with collagen
      fibrils. Recombinant alpha 1(XVI) collagen chains produced in embryonic kidney
      cells are able to form stable homotrimers, which are rapidly converted into
      smaller polypeptides after secretion into the culture medium. In this study, we
      investigated the biosynthesis of native type XVI collagen by immunoprecipitation
      of metabolically labeled human cells. Dermal fibroblasts and arterial smooth
      muscle cells were precipitated with three antibodies raised against distinct
      regions in the N- and C-terminal part of the human alpha 1(XVI) collagen chain. A
      disulfide-bonded polypeptide of 220 kDa was obtained from the culture medium,
      cells and extracellular matrix with all three antibodies. This polypeptide is
      sensitive to bacterial collagenase digestion and partially resistant to pepsin
      digestion, suggesting that it is the endogenous alpha 1(XVI) collagen chain.
      Pulse/chase experiments showed that the newly synthesized alpha 1(XVI) chains are
      secreted into the medium and deposited in the extracellular matrix in a time
      dependent manner. Unlike the recombinant chain, the native type XVI collagen does
      not undergo extensive proteolytic processing upon secretion. Both cell types
      deposit a substantial amount of the newly synthesized alpha 1(XVI) chain into the
      extracellular matrix, in which the 220-kDa polypeptide is the only product
      immunoprecipitated. There is little evidence for the presence of another
      constituent chain. The data are consistent with a nomotrimeric chain composition
      for type XVI collagen. No apparent difference exists in the rate of synthesis and
      secretion between fibroblasts and smooth muscle cells. Indirect
      immunofluorescence microscopy showed an extracellular distribution of type XVI
      collagen, which is located close to cells but not associated with fibrillar
      structures.

PMID- 9022685
TI  - Purification, characterization and subcellular localization of a type-1 ribosome
      inactivating protein from the sarcocarp of Cucurbita pepo.
AB  - The flesh of the fruit of Cucurbita pepo contains a type-1 ribosome-inactivating
      protein (RIP), which we named pepocin. Pepocin was purified to apparent
      homogeneity by acid fractionation, ion-exchange chromatography and adsorption
      chromatography. The protein was found to have a molecular mass of 26 kDa and a pI
      of about 9.9. It does not contain glycosidic linkages. The protein inhibits
      protein synthesis in a rabbit-reticulocyte lysate with an IC50 (concentration
      causing 50% inhibition) of 15.4 pM, and depurinates 28S rRNA in the ribosomes of
      the lysate in a manner identical to that of ricin A-chain and other RIP. The
      enzyme is also active on wheat-germ ribosomes and on Escherichia coli ribosomes.
      The sequence of the N-terminal 20 amino acids of the protein reveals a close
      relationship to other RIP. Immunoelectron-microscopic localization of pepocin in
      the sarcocarp shows that the protein is predominantly localized in intercellular
      spaces. In addition, the immunolocalized signals are observed in leaf
      intercellular spaces.

PMID- 9022686
TI  - Mutational analysis of the nor gene cluster which encodes nitric-oxide reductase
      from Paracoccus denitrificans.
AB  - The genes that encode the hc-type nitric-oxide reductase from Paracoccus
      denitrificans have been identified. They are part of a cluster of six genes
      (norCBQDEF) and are found near the gene cluster that encodes the cd1-type nitrite
      reductase, which was identified earlier [de Boer, A. P. N., Reijnders, W. N. M.,
      Kuenen, J. G., Stouthamer, A. H. & van Spanning, R. J. M. (1994) Isolation,
      sequencing and mutational analysis of a gene cluster involved in nitrite
      reduction in Paracoccus denitrificans, Antonie Leeu wenhoek 66, 111-127]. norC
      and norB encode the cytochrome-c-containing subunit II and cytochrome b
      containing subunit I of nitric-oxide reductase (NO reductase), respectively. norQ
      encodes a protein with an ATP-binding motif and has high similarity to NirQ from
      Pseudomonas stutzeri and Pseudomonas aeruginosa and CbbQ from Pseudomonas
      hydrogenothermophila. norE encodes a protein with five putative transmembrane
      alpha-helices and has similarity to CoxIII, the third subunit of the aa3-type
      cytochrome-c oxidases. norF encodes a small protein with two putative
      transmembrane alpha-helices. Mutagenesis of norC, norB, norQ and norD resulted in
      cells unable to grow anaerobically. Nitrite reductase and NO reductase (with
      succinate or ascorbate as substrates) and nitrous oxide reductase (with succinate
      as substrate) activities were not detected in these mutant strains. Nitrite
      extrusion was detected in the medium, indicating that nitrate reductase was
      active. The norQ and norD mutant strains retained about 16% and 23% of the wild
      type level of NorC, respectively. The norE and norF mutant strains had specific
      growth rates and NorC contents similar to those of the wild-type strain, but had
      reduced NOR and NIR activities, indicating that their gene products are involved
      in regulation of enzyme activity. Mutant strains containing the norCBQDEF region
      on the broad-host-range vector pEG400 were able to grow anaerobically, although
      at a lower specific growth rate and with lower NOR activity compared with the
      wild-type strain.

PMID- 9022687
TI  - Unfolding kinetics of bovine trypsinogen.
AB  - The unfolding kinetics of bovine trypsinogen were studied by a fluorescence
      detected stopped-flow technique at pH 5.8. Trypsinogen unfolding appeared to be a
      rather complex reaction. Two phases, fast (with a time constant in the
      millisecond range) and slow, were detected in the range 2-7 M guanidium chloride
      (GdmCl). The natural logarithm of the rate constant of the slow phase exhibited
      strong dependence on [GdmCl], changing from hundreds of seconds at low denaturant
      concentration to about 20 ms at 7 M GdmCl. The curvature of this dependence
      further suggests a complex mechanism of unfolding. Generally, similar kinetics
      were observed for the trypsinogen.Ca complex. Small differences could be noticed,
      however, for the fast phase. In agreement, Ca2+ influenced only this stage of the
      reaction. Analysis of the dependence of the time constant of the fast phase on
      [CaCl2] indicates that at 4 M GdmCl, trypsinogen.Ca unfolds about sixfold slower
      than free zymogen, and that native trypsinogen at 4 M GdmCl still exhibits high
      affinity for Ca2+. Limited data on trypsin unfolding show virtually an identical
      dependence of the slow phase on [GdmCl]; the fast phase, however was not
      observed. Moreover, in the 3-4.5 M GdmCl range, a separate phase was detected. It
      is postulated that this phase is a manifestation of the activation-domain
      unfolding. The Eyring plots for the fast phase of . trypsinogen and
      trypsinogen.Ca unfolding are linear, indicating little change in heat capacity
      for this stage of reaction. The slow step of unfolding, however, shows
      significant curvature which indicates a substantial increase in heat capacity.

PMID- 9022688
TI  - Structural characterisation of human recombinant glycohormones follitropin,
      lutropin and choriogonadotropin expressed in Chinese hamster ovary cells.
AB  - The alpha and beta chains from human recombinant gonadotropins follitropin,
      lutropin and choriogonadotropin expressed in CHO cells have been structurally
      characterised both at the protein and at the carbohydrate level by using advanced
      mass spectrometric procedures. The three alpha chains share the same amino acid
      sequence while they display different glycosylation patterns. The oligosaccharide
      structures detected belong to the complex-type glycans with different degree of
      sialylation. Partial proteolytic processing occurred at the N-terminus of the
      follitropin beta chain and at the C-terminus of the lutropin beta chain. The N
      linked glycans from the three beta chains were found to contain fucosylated and
      sialylated diantennary and triantennary complex-type structures. The follitropin
      beta chain showed the presence of N-acetyllactosamine repeats on the antennae.
      The overall structure of the recombinant glycohormones corresponds to their
      natural counterparts with the exception that sulphated terminal glycosylation is
      missing.

PMID- 9022689
TI  - Photoaffinity labelling of a DNA-binding site on the globular domain of histone
      H5.
AB  - We have labelled a DNA-binding site on the globular domain of histone H5 (GH5) by
      ultraviolet-activated cross-linking of a self-complementary 5-bromodeoxyuridine
      (5BrU)-substituted oligonucleotide with the sequence 5'-AGCGA5BrUATCGCT-3'. Cross
      linking was to His62, mainly to the protein backbone. This observation provides
      further support for the mode of binding of GH5 to DNA proposed on the basis of
      the similarity between the X-ray crystal structure of GH5 and the DNA-bound
      structures of catabolite activator protein and hepatic nuclear factor 3 gamma
      [Ramakrishnan, V. (1994) Curr. Opin. Struct. Biol. 4. 44-50].

PMID- 9022690
TI  - Location of cysteine and cystine residues in S-ribonucleases associated with
      gametophytic self-incompatibility.
AB  - S-Ribonucleases (S-RNases) that cosegregate with S-alleles in the styles of
      solanaceous and rosaceous plants are associated with gametophytic self
      incompatibility (GSI). The amino acid sequences of many S-RNases have been
      derived from cDNA sequences, but the state of half-cystines has not been
      clarified. We report the locations of the two free cysteine residues and four
      disulfide bridges of tobacco S6-RNase and of the four disulfide bridge of
      Japanese pear S4-RNase. The protein was first S-pyridylethylated at a low pH to
      selectively modify the free cysteines without thiol-disulfide exchange. The S
      pyridylethylated protein (PE-protein) was digested with Achromobacter protease I
      (API) at pH 6.5 then analyzed by liquid chromatography/electrospray-ionization
      mass spectrometry (LC/ESI-MS). This analysis showed that tobacco S6-RNase has two
      free cysteine residues, Cys77 and Cys95, and four disulfide bonds at Cys16-Cys21,
      Cys45-Cys94, Cys153-Cys182 and Cys165-Cys176. Similarly, four disulfide bonds
      were identified for pear S4-RNase, which bears no free cysteine, at Cys15-Cys22,
      Cys48-Cys92, Cys156-Cys195 and Cys172-Cys183. The eight cysteines forming these
      four disulfide bonds are conserved in all the known S-RNases, indicative that
      these cross-links are important in stabilizing the tertiary structures of the
      self-incompatibility-associated glycoproteins in the solanaceous and rosaceous
      families. The LC/ ESI-MS analysis also provided some structural informations
      regarding sugar chains attached to the S-RNases.

PMID- 9022691
TI  - Primary structure of stallion seminal plasma protein HSP-7, a zona-pellucida
      binding protein of the spermadhesin family.
AB  - The primary-structure of HSP-7, a 14-kDa protein isolated from stallion seminal
      plasma, has been determined, HSP-7 belongs to the spermadhesin protein family,
      shares 98% sequence identity with the boar seminal plasma protein AWN, and, like
      its boar homolog, displays zona-pellucida-binding activity. Despite these
      conserved structural and functional features, the equine and porcine
      spermadhesins differ in their topography on spermatozoa.

PMID- 9022692
TI  - Pregnenolone-7 beta-hydroxylating activities of yeast-expressed mouse cytochrome
      P450-1A1 and mouse-tissue microsomes.
AB  - In many tissues from different species, pregnenolone and dehydroepiandrosterone
      (DHEA) are hydroxylated mainly at the 7 alpha position by a cytochrome P450
      (P450)-containing microsomal enzyme complex. In addition, 7-hydroxysteroids have
      been shown to activate immune processes in mice. The reported production of 7
      beta-hydroxypregnenolone and 7 beta-hydroxy-DHEA was not supported by formal
      identification, and the P450 responsible for 7 alpha-hydroxylation and 7 beta
      hydroxylation of pregnenolone and DHEA have not been identified. Based on results
      of analyses by crystallization to constant specific activity and gas
      chromatography/mass spectrometry, we report that mouse-liver and mouse-brain
      microsomes carried out 7 beta-hydroxylation of pregnenolone and DHEA, and that
      yeast-expressed mouse cytochrome P450-1A1 (P450 1A1) transformed pregnenolone
      into 7 beta-hydroxypregnenolone (Km = 25.1 +/- 0.4 microM, turnover number = 979
      +/- 30 pmol.min-1.nmol-1 mouse P450 1A1). Neither 7-hydroxy derivatives of DHEA
      nor 7 alpha-hydroxypregnenolone was produced by P450 1A1. The presence of P450
      1A1 in liver and brain microsomes was shown by Western blot analysis, and
      induction of mouse P450 1A1 by beta-naphthoflavone resulted in increased 7 beta
      hydroxylation of pregnenolone in liver microsomes. Studies of the brain-microsome
      7 beta-hydroxylating enzyme with pregnenolone or DHEA gave Km of 5.0 microM and
      4.9 microM, respectively, and Vmax of 4.5 pmol.min-1.mg-1 and 6.1 pmol.min-1.mg
      1, respectively, and showed the absence of cross-inhibitions between the two
      steroids. These findings indicate that, in addition to unidentified P450, P450
      1A1 is involved in 7 beta-hydroxylation of pregnenolone and may contribute in
      part to the production of the 7-hydroxylated steroids necessary for activation of
      immune defenses.

PMID- 9022693
TI  - Two potential indole-3-acetaldehyde dehydrogenases in the phytopathogenic fungus
      Ustilago maydis.
AB  - The phytopathogenic basidiomycetc Ustilago maydis produces indole-3-acetic acid
      (IndCH2COOH) and indole-3-pyruvic acid (Ind-Prv) from tryptophan. Indole-3
      acetaldehyde (IndCH2CH2O) is the common intermediate in the conversion of Ind-Prv
      and tryptamine to IndCH2COOH. We purified an enzyme (Iad1) from U. maydis that
      catalyzes the NAD(+)-dependent conversion of IndCH2CH2O to IndCH2COOH and
      isolated corresponding cDNA and genomic clones. The identity of the cDNA clone
      was confirmed by expression in Escherichia coli and demonstration of enzymatic
      activity. In U. maydis, iad1-null mutants were generated by gene replacement. The
      ability to convert IndCH2CH2O to IndCH2COOH was at least 100-fold reduced in U.
      maydis iad1-null mutants grown in medium with glucose as carbon source. However,
      the iad1-null mutants were not diminished in their capacity to produce IndCH2COOH
      from tryptophan, indicating that IndCH2COOH formation from tryptophan apparently
      proceeds in the absence of IndCH2CH2O dehydrogenase activity under these
      conditions. Iad1 expression was strongly induced during growth on ethanol while
      under these conditions iad1-null mutants were unable to grow. This reveals that
      iad1 is primarily engaged in the conversion of ethanol to acetate. In iad1-null
      mutants we detected an additional NAD(+)-dependent IndCH2CH2O dehydrogenase
      activity that was induced during growth on L-arabinose but repressed in the
      presence of D-glucose. In arabinose-containing medium the conversion of
      tryptophan to IndCH2COOH was approximately 5-fold reduced in wild-type strains
      but 10-15-fold reduced in iad1-null mutant strains compared to IndCH2COOH
      formation in glucose-containing medium. In addition, the formation of Ind-Prv
      from tryptophan was abolished in wild-type and iad1-null mutant strains. During
      growth on arabinose, the conversion of tryptamine to IndCH2COOH was strongly
      favored suggesting that the glucose-repressible IndCH2CH2O dehydrogenase is
      required to convert IndCH2CH2O derived from tryptamine to IndCH2COOH.

PMID- 9022694
TI  - Lipid-binding properties of synthetic peptide fragments of human apolipoprotein A
      II.
AB  - Human apolipoprotein A-II (apo A-II) consists of three potential amphipathic
      helices of 17 residues each, which contribute to the lipid-binding properties of
      this apolipoprotein. The conformation and lipid-binding properties of these
      peptides, either as single-helix or as two-helix peptides, were investigated by
      turbidity, fluorescence, electron-microscopy and circular-dichroism measurements,
      and are compared in this article. The lipid affinity of shorter C-terminal
      segments of apo A-II was compared with those of the single-helix or two-helix
      peptides, to define the minimal peptide length required for stable complex
      formation. The properties of the apo-A-II-(13-48)-peptide were further compared
      with those of the same segment after deletion of the Ser31 and Pro32 residues,
      because the deleted apo-A-II-(13-30)-(33-48)-peptide, is predicted to form a long
      uninterrupted helix. The single helices of apo A-II could not form stable
      complexes with phospholipids, and the helix-turn-helix segment spanning residues
      13-48 was not active either. The apo-A-II-(37-77)-peptide and the apo-A-II-(40
      73)-peptide could form complexes with lipids, which appear as discoidal particles
      by negative-staining electron microscopy. The shortest C-terminal domain of apo A
      II able to associate with lipids to form stable complexes was the apo-A-II-(40
      73)-peptide, which consisted of the C-terminal helix, a beta-turn and part of the
      preceding helix. The shorter apo-A-II-(49-77)-peptide, and the helical apo-A-II
      (13-30)-(33-48)-peptide, could also associate with phospholipids. The complexes
      formed were, however, less stable, as they dissociated outside the transition
      temperature range of the phospholipid. These data suggest that the C-terminal
      pair of helices of apo A-II, which is the most hydrophobic pair, is responsible
      for the lipid-binding properties of the entire protein. The N-terminal pair of
      helices of apo A-II at residues 13-48 does not associate tightly with lipids. The
      degree of internal similarity and the cooperativity between the helical segments
      of apo A-II is thus less pronounced than in apo A-I or apo A-IV. The N-terminal
      and C-terminal domains of apo A-II appear to behave as two distinct entities with
      regard to lipid-protein association.

PMID- 9022695
TI  - Biosynthesis of acylpeptidolactones of the daptomycin type. A comparative
      analysis of peptide synthetases forming A21978C and A54145.
AB  - A21978C and A54145 are antibacterial 13-residue peptides with a medium-chain
      acylated amino terminus and a 10-residue lactone ring; they are produced by
      strains of Streptomyces roseosporus and Streptomyces fradiae, respectively. The
      structural differences in their peptide chains, which include amino acid
      replacements and modifications (L-Glu2-->L-Asn, L-Asn(OH)3-->L-Asp, Sar5-->Gly, L
      Ala6-->L-Orn, L-Lys8-->D-Ala, L-Asp(OMe)9-->L-Asp, L-Asn11-->D-Ser, and L-lle13-
      >L-Kyn; Sar = sarcosine; L-Orn = L-ornithine, L-Kyn = L-kynurenine), reside in
      the multienzymatic templates directing their biosynthesis. We have examined the
      peptide synthetases employing immunodetection and substrate activation detected
      by the amino-acid-dependent ATP-PP1-exchange reaction. Two different antibodies
      specific for actinomycin synthetase 2 and a peptide sequence characteristic of
      acyl-CoA-synthetases/peptide synthetases were applied. For the A21978 system two
      peptide synthetases of 670 and 240 kDa were detected, together with two similar
      proteins of 630 and 440 kDa occurring in varying amounts. The latter are
      suggested to be degradation products of an unstable multienzyme. Activation of L
      Asp, L-Thr, Gly, L-Orn, L-Ala and L-Ser were assigned to the high-molecular-mass
      components of 670, 630 and 440 kDa. The 240-kDa protein was purified to
      homogeneity and shown to catalyse activation of L-kynurenine. The A54145 system
      consisted of three peptide synthetases of 690, 590 and 250 kDa. Activations of L
      Asn. L-Thr and Gly were found. The 250-kDa synthetase was capable of activating
      isoleucine and valine. Both systems thus show a comparable organisation;
      implications for the modular construction of their peptide synthetases are
      discussed.

PMID- 9022696
TI  - Exploring the substrate specificities of alpha-2,6- and alpha-2,3
      sialyltransferases using synthetic acceptor analogues.
AB  - The acceptor specificities of rat liver Gal(beta 1-4)GlcNAc alpha-2,6
      sialyltransferase, recombinant full-length human liver Gal(beta 1-4)GlcNAc alpha
      2,6-sialyltransferase, and a soluble form of recombinant rat liver Gal(beta 1
      3/4)GlcNAc alpha-2,3-sialyltransferase were studied with a panel of analogues of
      the trisaccharide Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-O)(CH2)7CH3. These
      analogues contain structural variants of D-galactose, modified at either C3, C4
      or C5 by deoxygenation, fluorination, O-methylation, epimerization, or by the
      introduction of an amino group. In addition, the enantiomer of D-galactose is
      included. The alpha-2,6-sialyltransferases tolerated most of the modifications at
      the galactose residue to some extent, whereas the alpha-2,3-sialyltransferase
      displayed a narrower specificity. Molecular dynamics simulations were performed
      in order to correlate enzymatic activity to three-dimensional structure.
      Ineffective acceptors for rat liver alpha-2,6-sialyltransferase were shown to be
      inhibitory towards the enzyme; likewise, the alpha-2,3-sialyltransferase was
      found to be inhibited by all non-substrates. Modified sialyloligosaccharides were
      obtained on a milligram scale by incubation of effective acceptors with one of
      each of the three enzymes, and characterized by 500-MHz 1H-NMR spectroscopy.

PMID- 9022697
TI  - Structures of the antigenic O-polysaccharides of lipopolysaccharides produced by
      Actinobacillus actinomycetemcomitans serotypes a, c, d and e.
AB  - Actinobacillus actinomycetemcomitans is a gram-negative capnophilic coccobacillus
      that has been implicated in the etiology of certain forms of early-onset
      periodontitis as well as non-oral infections, mostly bacterial endocarditis. Five
      distinct serotypes of A. actinomycetemcomitans have been described. Although the
      O-polysaccharide (O-PS) of lipopolysaccharide (LPS) has been shown to define the
      serologic specificity for this species, only the structure of the O-PS of
      serotype b has been characterized. The focus of the current study was to define
      the structures of the O-PS of A. actinomycetemcomitans serotypes a, c, d and e.
      Structure determination was accomplished through the use of methylation,
      periodate oxidation, and one-dimensional and two-dimensional NMR methods. The O
      PS of A. actinomycetemcomitans (OMZ-542) serotype d had [alpha]D +15 degrees and
      was composed of D-glucose, D-mannose and L-rhamnose (L-Rha) in a molar ratio of
      1:2:1. Methylation, periodate oxidation, and two-dimensional 1H-NMR and 13C-NMR
      studies showed that the antigenic O-PS was a high-molecular-mass polymer composed
      of repeating tetrasaccharide units with the structure: [formula: see text] The O
      PS of the LPS produced by A. actinomycetemcomitans (ATCC 29523) serotype a had
      [alpha]D +150 degrees and was found to contain 6-deoxy-D-talose (6dTalp) and O
      acetyl (2:1) and was a high-molecular-mass polymer composed of O-acetyl
      substituted repeating disaccharide units with the structure: [formula: see text]
      The O-PS of the LPS of A. actinomycetemcomitans (SUNY 67) serotype c had [alpha]D
      -170 degrees and was composed of 6-deoxy-L-talose and O-acetyl (2:1). Structural
      analysis showed that the O-PS was a high-molecular-mass polymer of repeating
      disaccharide units with the structure: [formula: see text] The O-PS of the LPS of
      A. actinomycetemcomitans (OMZ 534) serotype e had [alpha]D +57 degrees and was
      composed of 2-acetamido-2-deoxy-D-glucose and L-rhamnose (1:1) and by chemical
      and NMR analysis was found to be a polymer of repeating disaccharide units with
      the structure: -->4)-alpha-D-GlcpNAc-(1-->3)-alpha-L-Rhap-(1-->.

PMID- 9022698
TI  - The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which
      catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and
      NADPH as cofactors and is inhibited by palmitoyl-CoA.
AB  - Reduction of enoyl-acyl-carrier-protein (ACP) substrates by enoyl-ACP reductase
      is a key regulatory step in fatty acid elongation of Escherichia coli. Two enoyl
      ACP reductase activities have been described in E. coli, one specific for NADH,
      the other for NADPH as cofactor. Because of their distinct enzymatic properties,
      these activities were ascribed to two different proteins. The NADH-dependent
      enoyl-ACP reductase of E. coli has previously been identified as the FabI
      protein, which is the target of a group of antibacterial compounds, the
      diazaborines. We now demonstrate that both enoyl-ACP reductase activities reside
      in FabI. In crude cell extracts of FabI-overproducing strains, both NADH
      dependent and NADPH-dependent enoyl-ACP reductase activities are increased.
      Mutations in the fabI gene that lead either to temperature-sensitive growth or
      diazaborine resistance result in the reduction of both activities. When FabI is
      purified in pH 6.5 buffers, the protein exhibits NADH-dependent and NADPH
      dependent reductase activities. Both enzymatic activities are inhibited by
      diazaborine. The NADPH-dependent enoyl-ACP reductase activity, however, turned
      out to be approximately eight times more resistant to diazaborine. The difference
      in sensitivity indicates that binding of either NADPH or NADH to FabI results in
      distinct changes in the configuration of the protein or, alternatively, it is
      different due to the different charge of the cofactors. These effects might be
      responsible for the differences in the enzymatic properties. Both reductase
      activities of the FabI protein are inhibited by physiologically relevant
      concentrations of palmitoyl-CoA, which might be important in regulating
      endogenous fatty acid biosynthesis in E. coli in the presence of exogenous fatty
      acids.

PMID- 9022699
TI  - Membrane-bound c-type cytochromes in Heliobacillus mobilis. Characterisation by
      EPR and optical spectroscopy in membranes and detergent-solubilised material.
AB  - The spectral and electrochemical parameters, as well as the orientations of the
      heme plane with respect to the membrane plane, of the c-type hemes present in
      membrane fragments from Heliobacillus mobilis were characterised by optical and
      EPR spectroscopy. Cytochrome C53, was thereby shown to represent at least four
      and possibly five heme species with the following characteristics: Em = -60 mV +/
      10 mV, g, = 2.92, 60 degrees; Em = +90 mV +/- 10 mV, g, = 2.92, 90 degrees; Em =
      +120 mV +/- 20 mV, g, = 3.03; and Em = +170 mV +/- 20 mV, g, = 3.03. The latter
      component may correspond to two hemes with redox midpoint potentials of Em = +160
      mV +/- 20 mV and Em = +180 mV +/- 20 mV (all Em values at pH 7.0). For the heme
      species having g, peaks at g approximately 3.03, determination of individual
      orientations was precluded due to the superposition of several differently
      oriented hemes. About one copy of each heme was found to be present per
      photosynthetic reaction centre, with the exception of the +120 mV component for
      which a stoichiometry of 2 hemes/reaction centre was obtained. The heme proteins
      were detergent-solubilised and partially purified. Three c-type cytochromes that
      migrated with apparent molecular masses of 18, 29 and 50 kDa were detected on
      SDS/PAGE. Optical redox titrations at pH 7.0 showed redox midpoint potentials of
      +160 mV +/- 10 mV for the 18-kDa cytochrome, and -60 mV +/- 10 mV, with possible
      contributions around +160 mV, for the 50-kDa cytochrome. A tentative attribution
      of heme species observed in membranes to the isolated heme proteins is presented.
      The results obtained on H. mobilis are compared with those reported for green
      sulphur bacteria.

PMID- 9022700
TI  - Blockade of the alpha 2-macroglobulin receptor/low-density-lipoprotein-receptor
      related protein on rat liver parenchymal cells by the 39-kDa receptor-associated
      protein leaves the interaction of beta-migrating very-low-density lipoprotein
      with the lipoprotein remnant receptor unaffected.
AB  - The nature of the liver binding site which is responsible for the initial
      recognition and clearance of chylomicron-remnants and beta-migrating very-low
      density lipoprotein (beta-VLDL) is under active dispute. We have investigated the
      effect of the 39-kDa receptor-associated protein (RAP) on the recognition site
      for activated alpha 2-macroglobulin and beta-VLDL on rat liver parenchymal cells
      in vivo and in vitro in order to analyze whether both substrates are recognized
      and internalized by the same receptor system. Radiolabelled trypsin-activated
      alpha 2-macroglobulin (alpha 2M-T) was cleared rapidly by the liver (maximal
      uptake of 80.8 +/- 1.0% of the injected dose). Prior injection of 5, 15, or 50 mg
      gluthathione-S-transferase-linked RAP (GST-RAP)/kg rat reduced the liver uptake
      to 62.2 +/- 2.3%, 59.3 +/- 1.1%, or 2.9 +/- 0.1% of the injected dose,
      respectively. Concurrently the serum decay was strongly delayed after injection
      of 50 mg GST-RAP/kg rat but this did not affect the serum decay and liver uptake
      of 125I-beta-VLDL. Binding studies with isolated liver parenchymal cells in vitro
      demonstrated that the binding of 125I-alpha 2M-T was 98% inhibited by GST-RAP
      with an IC50 of 0.3 microgram/ml (4.2 nM), whereas the binding of 125I-beta-VLDL
      and 125I-beta-VLDL + recombinant apolipoprotein E (rec-apoE) was unaffected by
      GST-RAP up to 50 micrograms/ml (700 nM). Also, the cell association and
      degradation of alpha 2M-T was blocked by RAP, while the association and
      degradation of beta-VLDL and beta-VLDL + rec-apoE were not influenced. The
      inhibitory effect of RAP on the cell association and degradation of alpha 2M-T
      lasted for 1-2 h of incubation at 37 degrees C. The binding of the radioiodinated
      RAP to isolated liver parenchymal cells was highly efficiently coupled to
      lysosomal degradation. Upon in vivo injection into rats, 125I-labeled RAP is
      rapidly cleared from the serum and taken up by the liver, which is also coupled
      to efficient degradation. Since RAP blocks binding of all known ligands to the
      alpha 2-macroglobulin receptor/low-density lipoprotein receptor-related protein
      (the alpha 2Mr/LRP) and at high concentrations the binding to the LDL receptor,
      we conclude that the initial binding and internalization of beta-VLDL by rat
      liver parenchymal cells is not mediated by the alpha 2Mr/LRP. The properties of
      binding of beta-VLDL to rat liver parenchymal cells points to an apoE-specific
      recognition site for lipoprotein remnants which differs from the alpha 2Mr/LRP,
      proteoglycans and the LDL receptor and is tentatively called the lipoprotein
      remnant receptor.

PMID- 9022701
TI  - Cloning, sequencing, mapping and hyperexpression of the ribC gene coding for
      riboflavin synthase of Escherichia coli.
AB  - The gene coding for riboflavin synthase of Escherichia coli has been cloned by
      marker rescue on a 6-kb fragment that has been sequenced. The riboflavin synthase
      gene is identical to the ribC locus and codes for a protein of 213 amino acids
      with a mass of 23.4 kDa. It was mapped to a position at 37.5 min on the physical
      map of the E. coli chromosome. The 3' end of the ribC gene is directly adjacent
      to the cfa gene, which codes for cyclopropane-fatty-acid synthase. This gene is
      followed by two open reading frames designated ydhC and ydhB, which are predicted
      to code for putative proteins with 403 amino acids and 310 amino acids,
      respectively. The gene ydhC is similar to genes coding for resistance against
      various antibiotics (cmlA, bcr) and probably codes for a transmembrane protein.
      The protein specified by ydhB shows sequence similarity to a large family of DNA
      binding proteins and probably represents a helix-turn-helix protein. The ydhB
      gene is directly adjacent to the regulatory gene purR. A 288-bp segment of the
      cfa gene has earlier been mapped incorrectly to a position adjacent to greA at 67
      min. The ribC gene was hyperexpressed in recombinant E. coli strains to a level
      of about 30% of cellular protein. The protein was purified to homogeneity by
      chromatography. The specific activity was 26000 nmol.mg-1.h-1. The protein
      sediments at a velocity of S20 = 3.8 S. Sedimentation-equilibrium centrifugation
      indicated a molecular mass of 70 kDa, consistent with a trimer structure. The
      primary structure of riboflavin synthase is characterized by internal sequence
      similarity (25 identical amino acids in the C-terminal and N-terminal parts
      suggesting two structurally similar folding domains.

PMID- 9022702
TI  - In vitro alpha-complementation of beta-galactosidase on a bacteriophage surface.
AB  - Surface display of large multimeric non-secreted proteins is advantageous on the
      bacteriophage lambda compared with the widely used filamentous phage systems. A
      model system, the alpha-complementation of beta-galactosidase, was used for both
      further general characterization of protein-protein interactions on the lambda
      tail tube surface and for specifically probing the structure of the phage
      displayed beta-galactosidase tetramer. In this complementation system, dimeric
      enzymatically inactive N-terminal deletion mutants of beta-galactosidase (alpha
      acceptors) interact with peptides whose sequences span the region of the deletion
      (alpha-peptides) with the subsequent formation of tetramers and restoration of
      activity. The lambda phage could tolerate incorporation into their tail tubes of
      a limited number of copies of V protein (gpV) subunits C-terminally modified with
      an active alpha-peptide. Purified alpha-peptide phage showed specific in vitro
      alpha-complementation with an alpha-acceptor extract; the features of this
      reaction suggested that each complemented monomer can directly associate with an
      alpha-peptide displayed within the same tail tube structure. In contrast to the
      alpha-peptide, attempts to surface display an alpha-acceptor protein in a similar
      manner were unsuccessful. The implications of this work for surface-display cDNA
      libraries are discussed.

PMID- 9022703
TI  - A conserved sequence region of scorpion toxins rendered immunogenic induces
      broadly cross-reactive, neutralizing antibodies.
AB  - Scorpion toxins constitute a family of proteins with a high degree of sequence
      diversity but a common mode of action. Neutralization of the toxic effects of
      scorpion stings by serotherapy is limited due to the various serotypes expressed
      by these proteins. We explored the possibility of raising antibodies to conserved
      parts of the toxins which could recognize several members of the family. We
      established the variability profile of a set of 25 scorpion toxin sequences, then
      evaluated systematically by peptide-scanning methods the antigenicity of one
      scorpion toxin. The most conserved regions were generally very poorly antigenic.
      One exception was the N-terminal region, which is both conserved and antigenic.
      Antibodies were raised in rabbits against an eight-residue synthetic peptide
      mimicking the N-terminal region. These peptide antibodies were cross-reactive
      with several scorpion toxins belonging to different serotypes and neutralized
      both the pharmacological effects (binding to rat brain synaptosomes) and the
      biological activity (toxicity in mice) of the parent toxin. The molecular model
      of the toxin indicates that antibody binding to residues 1-8 probably either
      masks some residue(s) of the N-terminus critical for the biological activity or
      overlaps with the epitope previously defined by neutralizing monoclonal antibody.
      These findings could open the way for new therapeutic strategies for the medical
      care of envenomations.

PMID- 9022704
TI  - Anaerobic crystallisation of an isopenicillin N synthase.Fe(II).substrate complex
      demonstrated by X-ray studies.
AB  - Isopenicillin N synthase (IPNS) was cocrystallised with ferrous sulphate and its
      substrate, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (Aad-Cys-Val). Vital
      to the successful procedure was the maintenance of a rigorously anaerobic
      environment. Hanging-drop vapour-diffusion crystallisation experiments, using
      lithium sulphate as the precipitant produced three crystal forms. Form I
      crystals, with a plate habit, diffracted X-rays to at least 0.11-nm resolution at
      the European Synchrotron Radiation Facility and belong to the space group
      P2(1)2(1)2(1), with unit-cell dimensions a = 4.68, b = 7.15, c = 10.10 nm. Their
      asymmetric unit contains a single IPNS.Fe(II).Aad-Cys-Val complex with a solvent
      content of 38.5%. Form II crystals, with a hexagonal habit, diffract X-rays to at
      least 0.21 nm resolution at the European Synchrotron Radiation Facility and
      belong to the space group P3(1)21, with unit-cell dimensions a = 10.10, b =
      10.10, c = 11.567 nm. Their asymmetric unit also contains a single
      IPNS.Fe(II).Aad-Cys-Val complex with a solvent content of 69.5%. Form III
      crystals, needles, do not show well-ordered diffraction. Although all three forms
      were initially produced in crystallisation experiments under identical
      conditions, appropriate micro and streak seeding allows selective crystallisation
      of form I or form II crystals. Extended X-ray-absorption fine-structure studies
      on a crystalline slurry of the form I crystals demonstrate the presence of an Fe
      S(Aad-Cys-Val) bond length of 0.234 +/- 0.003 nm.

PMID- 9022705
TI  - Evidence for glycosylation of the juvenile-hormone-binding protein from Galleria
      mellonella hemolymph.
AB  - The juvenile-hormone-binding protein (JHBP) from Galleria mellonella hemolymph,
      which is a member of the high-affinity/low-molecular-mass group of JHBP proteins,
      was found to be glycosylated. Glycosylation was confirmed by the following
      evidence. Carbohydrate gas-liquid chromatography analysis of the purified JHBP
      preparations showed the presence of a low amount of sugars (Man and GlcNAc were
      the major components). The JHBP electrophoretic band blotted onto nitrocellulose
      was stained with GlycoTrack (a reagent kit used for the detection of protein
      glycosylation) and showed strong binding of concanavalin A (ConA). JHBP was
      fractionated on a ConA-Sepharose 4B column into ConA-bound (strongly stained with
      ConA) and ConA-unbound (hardly stained with ConA) portions. Both fractions showed
      juvenile-hormone-binding activity and were glycosylated, as revealed by staining
      both of them with GlycoTrack. Electrospray-ionization mass spectrometry of JHBP
      suggested the presence of a small amount of presumably nonglycosylated protein
      (24988 Da) and five glycoforms, two of which (containing Man2GlcNAc, or
      Man2Fuc1GlcNAc2 chain) were not bound or were weakly bound to ConA, and three
      (with Man3GlcNAc2, Man5Fuc1GlcNAc2, or Man5GlcNAc2, chain) were present in the
      fraction strongly bound to ConA. In conclusion, the monosugar composition,
      GlycoTrack staining, ConA-binding properties and molecular mass analyses of JHBP
      supplied convincing evidence for its glycosylation and some information on the
      character of the oligosaccharide chains.

PMID- 9022706
TI  - Pre-tRNA 3'-processing in Saccharomyces cerevisiae. Purification and
      characterization of exo- and endoribonucleases.
AB  - We investigated ribonucleases from Saccharomyces cerevisiae which are active in
      pre-tRNA 3'-processing in vitro. Two pre-tRNA 3'-exonucleases with molecular
      masses of 33 and 60 kDa, two pre-tRNA 3'-endonucleases with molecular masses of
      45 kDa/60 kDa and 55 kDa and 70-kDa 3'-pre-tRNase were purified from yeast whole
      cell extracts by several successive chromatographic purification steps. The
      purified exonucleases are non-processive 3'-exonucleases that catalyze the
      exonucleolytic processing of 3'-trailer sequences of pre-tRNAs to produce mature
      tRNAs. The 45-kDa/60-kDa 3'-endonuclease is tRNA-specific and catalyzes the
      processing of pre-tRNAs in a single endonucleolytic step. Two isoenzymes of this
      activity (p45 and p60) were identified by chromatography. The second
      endonuclease, p55, is dependent on monovalent ions and cleaves about three
      nucleotides downstream the mature 3'-end. All of the purified 3'-pre-tRNases
      accept homologous as well as heterologous pre-tRNA substrates. Pre-tRNAs carrying
      a 5'-leader are processed with almost the same efficiency as those lacking this
      5'-leader. Mature tRNAs carrying the CCA 3'-sequence and tRNA pseudogene products
      carrying mutations in the mature domain are processed by the 3'-exonucleases, not
      by the 3'-endonucleases. The specific endonuclease p45/p60 discriminates between
      UUUOH as a 3'-flank, which is cleaved, and the CCA 3'-end of mature tRNAs, which
      is not cleaved. This study suggests that several 3'-pre-tRNases are active on
      tRNA precursors in vitro and might therefore in pre-tRNA 3'-processing in yeast,
      partly in a cooperative manner.

PMID- 9022707
TI  - The lipase from Staphylococcus aureus. Expression in Escherichia coli, large
      scale purification and comparison of substrate specificity to Staphylococcus
      hyicus lipase.
AB  - The genes coding for the mature part of the lipases from Staphylococcus aureus
      NCTC8530 and Staphylococcus hyicus have been cloned and overexpressed in
      Escherichia coli as fusion proteins with an N-terminal hexa-histidine tag. The
      enzymes accumulated in the cytoplasm and were purified using sequential
      precipitation with protamine sulphate and ammonium sulphate, followed by metal
      affinity and hydroxyapatite chromatography. The yield of pure lipase was 4.5 mg/g
      wet cells for S. aureus lipase and 13 mg/g for S. hyicus lipase. The purified
      enzymes need calcium for activity, albeit with different affinities, and a low
      residual activity was found in the absence of calcium. In contrast to S. hyicus
      lipase, not only strontium but also barium can replace calcium with full
      retention of activity of S. aureus lipase. Whereas S. hyicus lipase is optimally
      active at pH 8.5, the optimum pH for enzymatic activity for S. aureus lipase was
      found to be pH 6.5. The S. aureus lipase has a narrow substrate specificity:
      short-chain triacylglycerols and acyl esters of both p-nitrophenol and
      umbelliferone are readily degraded, whereas medium- and long-chain lipids, as
      well as phospholipids, are poor substrates. In contrast, S. hyicus lipase prefers
      phospholipids as substrate and hydrolyses neutral lipids irrespective of their
      chain length. The results are discussed in view of the large sequence similarity
      between both lipases.

PMID- 9022708
TI  - Mathematical models for determining metabolic fluxes through the citric acid and
      the glyoxylate cycles in Saccharomyces cerevisiae by 13C-NMR spectroscopy.
AB  - We propose, first, a practical method for studying the isotopic transformation of
      glutamate or any other metabolite isotopomers in the citric acid and the
      glyoxylate cycles; second, two mathematical models, one for evaluating the flux
      through the citric acid cycle and the other for evaluating the flux through the
      latter coupled to the glyoxylate cycle in yeast. These models are based on the
      analysis of 13C-NMR spectra of glutamate obtained from Saccharomyces cerevisiae,
      NCYC strain, fed with 100% enriched [2-13C]acetate. The population of each
      glutamate isotopomer, the change in intensity of each multiplet component or the
      enrichment of any glutamate carbon is expressed by a specific analytical equation
      from which the flux in the citric acid and the glyoxylate cycles can be deduced.
      The aerobic metabolism of 100% [2-13C]acetate in acetate-grown S. cerevisiae
      cells was studied as a function of time using 13C-NMR. 1H-NMR and biochemical
      techniques. The C1 and C6 doublet and singlet of labeled trehalose increase
      continuously with time indicating that there is no isotopic transformation
      between trehalose isotopomers even though the corresponding formation rates are
      different. By contrast, the glutamate C4 singlet increases then decreases with
      time. The C4 doublet, which is lower than the singlet for t < 60 min, increases
      continuously and becomes higher than the singlet for t > 90 min. A similar
      observation was made for the C2 resonance singlet and doublet. In addition, the
      glutamate C2 multiplet consists of only seven instead of nine peaks as in random
      labeling. These results agree well with our models and demonstrate that, in the
      presence of acetate, anaplerotic carbon sources involved in the synthesis of
      acetyl-CoA are negligible in yeast. The flux in the citric acid cycle was deduced
      from a plot of the C4 area versus incubation time, while the flux within the
      glyoxylate cycle was determined from the relative intensity of the glutamate C4
      doublet and singlet. The fluxes in the citric acid and the glyoxylate cycles were
      found to be comparable. The proportion of glutamate in isotopic exchange with the
      citric acid cycle is about 2.5% min1 in yeast.

PMID- 9022709
TI  - Purification and spectroscopic characterization of a recombinant chloroplastic
      hemoglobin from the green unicellular alga Chlamydomonas eugametos.
AB  - Hemoglobins (Hb), which have the important task of delivering molecular oxygen by
      facilitating its reversible binding to the heme, are now thought to have evolved
      in all groups of organisms including prokaryotes, fungi, plants and animals. Our
      recent finding of a light-inducible chloroplastic Hb in the green unicellular
      alga Chlamydomonas eugametos has further extend this idea, while raising
      questions about the function that an Hb could play in a high oxygen environment
      such as in the chloroplast. In order to understand the role played by this new
      Hb, we have undertaken its biochemical characterization. To facilitate the
      characterization of Chlamydomonas Hb, which represents less than 0.01% of the
      soluble protein in the green alga, the protein has been expressed in Escherichia
      coli and purified to apparent homogeneity. The purified recombinant protein
      possesses a non-covalently bound iron-protoporphyrin IX heme. The oxy form of the
      recombinant Hb. purified directly from bacterial cells, is very stable, with a
      measured half-life of 7 days at pH 8 and has an ultraviolet/visible spectrum
      similar to those of the related cytoplasmic Hbs of the ciliated protozoa
      Paramecium and Tetrahymena and of the cyanobacterium Nostoc commune. In contrast
      to what has been reported for oxymyoglobins and oxyhemoglobins, the dioxygen
      molecule bound to the L1637 Hb can be reduced by the electron-transfer mediator
      phenazine methosulfate in the presence of NADPH, indicating that the heme pocket
      of Chlamydomonas Hb may be more accessible to small molecules. With regard to
      this we found that when the small reducing agent sodium dithionite is used to
      reduce the met form, it must be removed anaerobically from the Hb prior to
      oxygenation of the protein to stably produce the oxy form. Otherwise, the oxy
      form is obtained readily from the met form under an oxygenic atmosphere when
      ferredoxin and ferredoxin NADP+ reductase are used to enzymically reduce the Hb.
      Finally, the spectra of the deoxy and met forms were unusual, the heme being
      partly low-spin at physiological pH. These results confirm the existence of a
      reversible oxygen-binding protein in the chloroplast of C. eugametos. The unusual
      spectral and biochemical properties of the protein may reflect a specialized
      function for this Hb.

PMID- 9022711
TI  - Identification and characterization of three isotypes of protein phosphatase
      inhibitor-2 and their expression profiles during testis maturation in rats.
AB  - cDNAs for three isotypes of inhibitor-2(I-2), I-2 alpha 1, I-2 alpha 2 and I-2
      beta were isolated from a rat testis library. I-2 alpha 2 and I-2 beta are new
      forms. The former is an alternatively spliced form of I-2 alpha 1, encoding a
      protein with substitution of three amino acids for 14 amino acids of the I-2
      alpha 1 protein at the C-terminus. The latter is derived from a different gene
      and encodes a 126-amino-acid protein having highly conserved regions with the I-2
      alpha 1 protein from amino acid positions 22-47 and 111-126. I-2 alpha 2 and I-2
      beta are expressed exclusively in the testis, and the expressions of all three
      forms of I-2 coincide with sperm cell maturation. The half-maximal inhibitory
      concentration of the GST-I-2 alpha 2 fusion protein on the PP1 gamma 2 catalytic
      subunit is the same as that of GST-I-2 alpha 1, being 10 nM. However, the half
      maximal inhibitory concentration of GST-1-2 beta is 100-fold higher, being 1
      microM. GST-I-2 beta showed no competition with GST-I-2 alpha 1. and its
      biological significance is unknown.

PMID- 9022710
TI  - Temporins, antimicrobial peptides from the European red frog Rana temporaria.
AB  - A cDNA library from the skin of Rana temporaria has been screened using a cDNA
      fragment probe that encodes the signal peptide of the precursor of esculentin
      from the skin secretion of Rana esculenta. With this approach, the cDNAs encoding
      the precursors of three peptides were isolated. Subsequently, the peptides
      predicted from the sequence of the cloned cDNAs as well as several structurally
      related peptides could be isolated from the skin secretion of R. temporaria.
      These peptides, which were named temporins, have a length of 10-13 residues and
      show some sequence similarity to hemolytic peptides isolated from Vespa venom
      [Argiolas, A. & Pisano, J. J. (1984) J. Biol. Chem. 259, 10106-10111]. Natural
      and synthetic temporins have antibacterial activity against gram-positive
      bacteria, but they are not hemolytic. Temporins are the smallest antibacterial
      peptides hitherto found in nature.

PMID- 9022712
TI  - Effects of ultraviolet-B radiation on photosystem II of the cyanobacterium
      Synechocystis sp. PCC 6083.
AB  - The effects of ultraviolet-B radiation (280-320 nm) on photosystem II of
      Synechocystis sp. PCC 6303 were investigated at the functional and structural
      levels. Loss of oxygen-evolving and electron-transport activity, measured by
      various techniques including Clark electrode polarography, fluorescence induction
      and fluorescence relaxation after a single turnover flash, are discussed in terms
      of two types of damage caused by ultraviolet-B radiation: (a) depletion of the
      plastoquinone pool; (b) perturbation and degradation of the D1 protein, with
      cleavage in the second transmembrane segment. These findings are in full
      agreement with those obtained, both in vivo and in vitro for higher plants for
      which a donor-side mechanism involving the water-splitting Mn cluster has been
      proposed for the main cleavage of the D1 protein. At the structural level,
      complete disruption of the photosystem II core is documented as a consequence of
      (or in parallel with) degradation of the D1 protein. From this point of view,
      ultraviolet-B-induced photoinhibition is unlike the visible-induced type and less
      susceptible to repair by synthesis and reinsertion of new D1 protein.

PMID- 9022713
TI  - cDNA cloning, expression and characterization of nitric-oxide synthase from the
      salivary glands of the blood-sucking insect Rhodnius prolixus.
AB  - Rhodnius prolixus, a blood-sucking bug, is a unique insect that is known to
      produce nitric oxide (NO) in the salivary glands to use as a vasodilator for
      blood sucking. We report here the cloning of the NO synthase (NOS) cDNA from
      these salivary glands and its expression in a baculovirus system. This cDNA
      encodes a protein of 1174 amino acids with a calculated molecular mass of 132,331
      Da. The primary structures of mammalian NOS, including the putative cofactor
      recognition sites for heme, tetrahydrobiopterin (BH4), calmodulin. FMN, FAD and
      NADPH are all conserved in salivary-gland NOS. Recombinant salivary-gland NOS
      differed from nerve NOS and endothelial NOS in that it lacked a large N-terminal
      domain and an N-terminal myristylation sequence, respectively. Salivary-gland NOS
      produced in a baculovirus system showed NOS activity and demonstrated that
      salivary-gland NOS was soluble and was Ca2+ and calmodulin dependent, similarly
      to mammalian constitutive NOS isoforms. Recombinant salivary-gland NOS was
      purified to near homogeneity and migrated at 130 kDa on SDS/PAGE.

PMID- 9022714
TI  - Structure/function relationships in human phenylalanine hydroxylase. Effect of
      terminal deletions on the oligomerization, activation and cooperativity of
      substrate binding to the enzyme.
AB  - Amino-terminal and carboxy-terminal deletion mutagenesis have been used to
      identify structurally and functionally critical regions of recombinant wild-type
      human phenylalanine hydroxylase (wt-hPAH; Ser2-Lys452). The wild-type form
      consisted of dimeric and tetrameric forms in equilibrium, and only the isolated
      tetrameric form showed positive cooperativity of substrate (L-Phe) binding (Hill
      coefficient h = 2.2, S0.5 = 154 microM). The deletion mutants lacking the carboxy
      terminal 24 amino acids hPAH (Ser2-Gln428) and hPAH(Gly103-Gln428) formed
      catalytically active dimers, and incubation with L-Phe did not promote the
      formation of tetramers, a characteristic property of dimeric wt-hPAH. The
      carboxyterminus thus seems to contain a motif required for dimer-dimer
      interaction in wt-hPAH. The deletion mutants hPAH(Asp112-Lys452), hPAH(Ser2
      Gln428) and hPAH(Gly103-Gln428) were all activated by prior incubation with L
      Phe, but did not reveal any positive cooperativity of substrate binding (h =
      1.0). The activation by L-Phe was accompanied by a measurable conformational
      change (as probed by intrinsic fluorescence spectroscopy) only in the enzyme
      forms containing the amino-terminal sequence. i.e. wt-hPAH and the Ser2-Gln428
      mutant. The amino-terminal deletion mutants hPAH(Asp112-Lys452) and hPAH(Gly103
      Gln428) revealed high specific activity, increased apparent affinity for L-Phe
      (S0.5 = 60 microM) and a tryptophan fluorescence emission spectrum similar to
      that of the L-Phe-activated wt-hPAH. Moreover, prior incubation of the enzyme
      forms with lysophosphatidylcholine, a commonly used activator of the PAH, only
      increased the activity of those forms containing the wt-hPAH amino-terminal
      sequence. Our results are compatible with a model in which incubation of wt-hPAH
      with L-Phe induces both a conformational change (with cooperativity in the
      tetrameric enzyme) which relieves the inhibition imposed by the amino-terminal
      domain to the high-affinity binding of L-Phe, and an additional activation, as
      observed for the truncated forms lacking the amino-terminal.

PMID- 9022715
TI  - Molecular cloning of Limulus alpha 2-macroglobulin.
AB  - The American horseshoe crab Limulus polyphemus contains alpha 2-macroglobulin
      (alpha 2M) in the hemolymph plasma and hemocytes. alpha 2M from Limulus shows
      many of the typical characteristics of mammalian alpha 2M, including the presence
      of an internal thiol-ester, reactivity with a diversity of endopeptidases, a
      unique proteinase-trapping mechanism, and reactivity with the mammalian alpha 2M
      receptor. Additionally, Limulus alpha 2M has the unique property that it
      regulates the limulin-based hemolytic system of the plasma. A cDNA encoding
      Limulus alpha 2M has been obtained from a hemocyte cDNA library. The open reading
      frame encodes an N-terminal signal sequence of 25 amino acid residues and a
      mature protein of 1482 residues. The entire amino acid sequence is similar to
      those of the mammalian alpha 2Ms (28-29% identity) and contains common features
      found in mammalian alpha 2Ms. a bait region, an internal thiol-ester site, and a
      receptor-binding domain. However, the N-terminal portion (positions 24-105) has
      no sequence similarity with those of mammalian alpha 2Ms, and it is structurally
      related to that of the human complement factor C8 chain, consistent with a role
      for Limulus alpha 2M in host defense. The component sugar analysis of Limulus
      alpha 2M showed the existence of a complex type of oligosaccharide chain similar
      to those of mammalian alpha 2M. However, unlike mammalian alpha 2M, no sialic
      acid was detected in Limulus alpha 2M and it contained approximately 3 mol/mol N
      acetylgalactosamine, suggesting the presence of O-linked sugar chains, which have
      not been found in mammalian alpha 2M. Expression of alpha 2M was detected in
      hemocytes, but not in hepatopancreas, heart, stomach, intestine, coxal gland,
      brain and skeletal muscle. Furthermore, immunoblotting of large and small
      granules of the hemocytes with antiserum against alpha 2M indicated the presence
      of the alpha 2M in large granules. Trypsin-treated Limulus alpha 2M, but not the
      native alpha 2M, displaced methylamine-treated human 125I-alpha 2M from the human
      alpha 2M receptor with a Kd of 30 nM, suggesting conservation of the proteinase
      clearance mechanisms between mammalian and arthropod evolutionary lineages.

PMID- 9022716
TI  - Hepatic production of 1,5-anhydrofructose and 1,5-anhydroglucitol in rat by the
      third glycogenolytic pathway.
AB  - A unique anhydrohexulose, 1,5-anhydrofructose (1,5AnFru) has been detected in rat
      livers. Here we describe a microanalytical method for 1,5AnFru using GC/MS and
      report results on the distribution and production of 1,5 AnFru in rats. The
      highest levels of 1,5AnFru were found in the liver (0.43 microgram/g wet tissue)
      and appreciable amounts were detected in adrenal gland and spleen (0.12
      microgram/g and 0.09 microgram/g, respectively). Other organs contained lower
      amounts while plasma contained virtually no detectable 1,5AnFru. We also
      demonstrated that 1,5AnFru is produced in the cytosol fraction of rat liver
      homogenate when an alpha-1,4-glucan or glycogen was added; 1,5AnFru was readily
      reduced to 1,5-anhydroglucitol with NADPH or at a reduced efficiency with NADH in
      the presence of a Mono Q chromatographic fraction obtained from the same cytosol
      preparation. Based on these results, we propose the existence of a third
      degradation pathway, in addition to the phosphorolytic and hydrolytic reaction
      sequences, from glycogen to 1,5-anhydroglucitol via 1,5AnFru in mammals. However,
      the physiological significance of 1,5AnFru and this putative minor glycogenolytic
      pathway in mammals remains obscure.

PMID- 9022717
TI  - Glucocorticoid receptor lacking the tau 1 transactivation domain is a gene
      specific regulator of the wild-type glucocorticoid-receptor activity.
AB  - The glucocorticoid receptor (GR) contains a major transactivation function (tau
      1), located in the N-terminal domain. tau 1 contributes to about 80% of the
      ligand-inducible transcriptional activity of GR. In this study, we show that GR
      devoid of tau 1 (symbol: see text] GR) can inhibit activation of gene expression
      by wild-type GR but this does not occur for all target genes. Activation of the
      mouse mammary tumor virus promoter by wild-type GR in transiently transfected
      chinese hamster ovary (CHO) cells lacking endogenous GR was repressed by
      cotransfecting [symbol: see text] GR. This effect was proportional to the amount
      of transfected [symbol: see text] GR and was not due to squelching. A moderate
      expression level of stably transfected [symbol: see text] GR mutant was also
      shown to repress the transcriptional activity of endogenous GR present in rat
      skeletal myoblast L8 cells. Glucocorticoid mediated down regulation of endogenous
      GR gene expression can be blocked by the [symbol: see text] GR mutant in stably
      transfected L8 cells. In contrast, no inhibition was observed on glucocorticoid
      induction of the endogenous glutamine synthetase gene in L8 cells. However,
      glucocorticoid induction of a reporter gene driven by the chicken glutamine
      synthetase promoter was inhibited by [symbol: see text] GR in L8 cells. Stable
      expression of wild-type GR in CHO cells rendered the cells glucocorticoid
      responsive with regard to glutamine synthetase induction but coexpression of
      [symbol: see text] GR did not repress induction of the endogenous glutamine
      synthetase gene expression by wild-type GR. Expression of [symbol: see text] GR
      alone in CHO cells did not render the glutamine synthetase gene glucocorticoid
      responsive, indicating that [symbol: see text] GR has no transcriptional activity
      on the glutamine synthetase gene. We conclude from these results that the
      structure of glucocorticoid-response elements within target genes may be very
      critical for the ability of the mutant receptor to exhibit a dominant negative
      effect.

PMID- 9022718
TI  - Cytopathology today: challenges and opportunities.

PMID- 9022719
TI  - Automated screening for cervical cancer: diagnostic decision procedures.

PMID- 9022720
TI  - Our journey towards improved accuracy in cytology: the role of new technologies.

PMID- 9022721
TI  - Comparison of the CytoRich system with conventional cervical cytology.
      Preliminary data on 2,032 cases from a clinical trial site.
AB  - OBJECTIVE: To compare the CytoRich system with conventional cervical cytology in
      a university medical center hospital laboratory. STUDY DESIGN: The CytoRich
      system combines liquid preservation, selective reduction of blood/inflammation,
      thin-layer preparation and discrete staining. Two thousand thirty-two parallel
      conventional and CytoRich samples were examined as part of a multicenter trial of
      the CytoRich/AutoCyte systems. Same-patient conventional and CytoRich slides were
      submitted to separate cytotechnologists blindly. The results were compared, and
      all nonmatching sample pairs were reviewed again. A consensus diagnosis was
      derived for all cases. The initial readings of the CytoRich and conventional
      smears were compared with each other and with the consensus diagnosis. RESULTS:
      Of the 148 squamous intraepithelial lesions (SILs) found by either method, 85%
      were found by CytoRich, while only 58.5% were found by conventional smear. As
      compared with the consensus diagnosis, CytoRich slides had 86.7% sensitivity for
      SIL and 99.1% specificity, while the conventional slides had 63.6% sensitivity
      and 99.7% specificity. Consensus review resulted in upgrading to SIL in 1.8% of
      conventional slides and 1.4% of CytoRich slides. The biopsy correlation results
      were similar for the two methods. CONCLUSION: The CytoRich system affords
      excellent cellular presentations and superior sensitivity for SILs when compared
      to the conventional technique.

PMID- 9022722
TI  - Clinical trials of the CytoRich specimen-preparation device for cervical
      cytology. Preliminary results.
AB  - OBJECTIVE: To obtain preliminary data on the Roche CytoRich thin-layer system for
      the preparation of gynecologic cytology specimens, derived from a preclinical
      startup evaluation of the instrument and comparing the CytoRich method to
      conventional smears. STUDY DESIGN: At six different clinical sites, 286 pairs of
      conventional and CytoRich slides derived from the same patient sample were
      compared for the following: final Bethesda classification diagnosis, specimen
      adequacy and presence of microorganisms. RESULTS: The study showed agreement
      between the methods for an exact Bethesda diagnosis in 78% and agreement within
      one Bethesda diagnosis category in 95%. The CytoRich method diagnosed more cases
      of squamous intraepithelial lesion (SIL) than did the conventional method, and
      the differences in SIL detection were statistically significant. The CytoRich
      method identified similar numbers of cases with microorganisms as did the
      conventional smears, and the CytoRich system improved overall specimen adequacy
      as compared to the conventional method, with fewer cases of unsatisfactory and
      less-than-optimal smears. CONCLUSION: The CytoRich method may improve the overall
      sensitivity and specificity of the cervical cytology procedure. Clinical trials
      to verify these preliminary data are ongoing.

PMID- 9022723
TI  - The ThinPrep Pap test. A review of clinical studies.
AB  - OBJECTIVE: To review the literature describing the use of the ThinPrep system in
      gynecologic cytology. STUDY DESIGN: Clinical trials of the ThinPrep Beta and the
      ThinPrep 2000 performed in the United States were reviewed. In each a single
      sample was used to first prepare a conventional slide and the remainder to
      perform a ThinPrep cervical cytologic test. Slides were examined in a blind
      fashion by cytotechnologists and classified according to Bethesda System
      terminology. RESULTS: The ThinPrep test provided significantly more effective
      detection of low grade intraepithelial neoplasia or more severe diagnoses without
      loss of diagnostic specificity. The ability of the ThinPrep system to detect
      infection and reactive cellular changes was equivalent to or better than that of
      the conventional cytologic smear. Specimen adequacy was significantly enhanced
      with the ThinPrep test by reducing the number of cases classified as
      "Satisfactory but limited by...". CONCLUSION: The ThinPrep test offers increased
      detection of cervical disease and a clear improvement in specimen adequacy. In
      addition to potentially lowering the false negative rate of cervical smears,
      collection of cells in liquid medium allows additional testing, such as human
      papillomavirus typing and computer imaging, to provide a more comprehensive
      diagnosis than that obtainable with the cervical cytologic test.

PMID- 9022724
TI  - Specimen adequacy of ThinPrep sample preparations in a direct-to-vial study.
AB  - OBJECTIVE: To assess specimen adequacy of the ThinPrep slide preparation method
      in routine use. STUDY DESIGN: Two studies, a feasibility study of 299 women and a
      clinical study of 499 women, were conducted. A broom-type collection device was
      used and rinsed directly into Pre-servCyt vials. Slides were prepared with the
      ThinPrep 2000 device, screened and classified according to the Bethesda System.
      The proportion of ThinPrep slides described as "Satisfactory But Limited By: No
      Endocervical Component (SBLB:No ECC)" was then compared to the proportion of
      SBLB: No ECC slides found on conventional smears in a previously conducted
      clinical trial of over 7,000 patients. RESULTS: For the feasibility study the
      proportion of ThinPrep slides described as SBLB: No ECC was 9.36% as compared to
      the clinical trial combined rate of 9.4% for conventional smears. For the
      clinical study, 4.96% of ThinPrep slides were SBLB:No ECC as compared to the 4.4%
      SBLB:No ECC rate for conventional smears from the same clinical trial. The
      proportions were statistically equivalent for both studies. CONCLUSION: It is
      expected that the rate of representing endocervical component will be maintained
      when the ThinPrep preparation method is used routinely in place of the
      conventional cytologic smear method.

PMID- 9022725
TI  - AutoPap 300 QC system scoring of cervical smears without "epithelial cell
      abnormalities".
AB  - OBJECTIVE: To examine four morphologic features other than epithelial abnormality
      to identify if they are associated with a high quality control (QC) score with
      the AutoPap 300 QC system. STUDY DESIGN: A total of 180 slides (140 with a high
      QC score and 40 with a low QC score [the control group]) were manually reviewed,
      and four morphologic features were assessed while blind to the QC score, as
      follows: adequacy, epithelial fragments and clumps, cytohormonal pattern, and
      diagnostic categories within normal limits and benign cellular changes (BCC).
      RESULTS: Both atrophy and a diagnosis of BCC were associated with a high QC score
      at a statistically significant level. CONCLUSION: Certain characteristics of the
      slide population submitted for AutoPap QC review could have an impact on the
      overall laboratory workload (QC review rate). There are opportunities to optimize
      the workload of the laboratory when using AutoPap for QC selection.

PMID- 9022726
TI  - Enhancing the performance of the AutoPap 300 QC system with optimal staining and
      presentation of cervical smears.
AB  - OBJECTIVE: To optimize the staining and presentation of slides for the AutoPap
      300 QC System, an automated cytology screening system which examines
      conventionally prepared cervical smears, and to assess subsequent scanning and
      scoring rates and compare them to those of laboratories not adopting these
      changes. STUDY DESIGN: In this study, procedures were developed for optimal
      presentation and staining of slides for the AutoPap System in response to
      observations made in preclinical trials. Three thousand eight hundred fifty-five
      slides were then submitted to the device for analysis in a prospective, blind,
      clinical evaluation study. The scanning and scoring rates were compared to those
      of a cohort of 12,525 slides that were analyzed in other laboratories which had
      not adopted these procedures. RESULTS: Two hundred forty (6.2%) slides failed
      scanning due to physical defects. An additional 70 slides (2.0% of scanned
      slides) did not complete scoring due to staining limitations. The laboratories in
      the clinical trials that had not adopted these preanalytic method changes had
      higher scanning failure rates due to physical limitations (15.0%) and incomplete
      scoring rates due to staining limitations (6.2%). CONCLUSION: The present study
      demonstrated that the performance of the AutoPap 300 is enhanced by meticulous
      attention to preanalytic staining and presentation procedures.

PMID- 9022727
TI  - AutoPap system performance in screening for low prevalence and small cell
      abnormalities.
AB  - OBJECTIVE: To summarize the design principles of the AutoPap System evaluation
      score by evaluating slides having a low prevalence of abnormal cells and small
      cell abnormalities and assessing the evaluation score as a diagnostic tool. STUDY
      DESIGN: Data from two clinical studies conducted using the AutoPap System and
      data obtained from the evaluation score training slides were analyzed to
      demonstrate the effectiveness of the evaluation score. The clinical studies
      included a prospective, intended-use study involving approximately 13,000 slides
      and a comprehensive sensitivity study using approximately 1,200 slides from five
      laboratories. The evaluation score training set consisted of 4,174 slides from 10
      laboratories. RESULTS: The robust design of the AutoPap evaluation score was
      demonstrated by similar detection capabilities and sensitivities to slides having
      either a low or high prevalence of abnormal cells. No significant difference in
      performance was detected between the small cell slides and the comparison groups
      of carcinoma in situ and invasive squamous carcinoma having normal-sized abnormal
      cells. In addition, the evaluation scores corresponded well to the diagnostic
      severity of the slides.

PMID- 9022728
TI  - PAPNET Testing System. Technical update.
AB  - OBJECTIVE: To extensively test the functional integrity of the PAPNET Testing
      System, a computer-assisted cervical smear rescreening device, to ensure
      performance and reliability. STUDY DESIGN: Various system and subsystem testing
      methodologies were used to verify that the PAPNET Scanning Station performed
      according to specifications. Using synthetic and biologic slides, proper
      operation of the system in its intended use environment was verified. An
      automated system test was employed to demonstrate the ability of the system to
      detect cytologic abnormality. Several tests were performed throughout the
      production process and normal operation to ensure subsystem operations. RESULTS:
      The testing methodologies were shown to provide accurate measurements of scanning
      performance. CONCLUSION: Methodical testing and implementation of technologic
      enhancements ensure system performance and reliability. When used with
      microscopy, PAPNET testing provides the means to improve the accuracy of cervical
      cytology.

PMID- 9022729
TI  - Negative cervical smears before CIN 3/carcinoma. Reevaluation with the PAPNET
      Testing System.
AB  - OBJECTIVE: To test the effectiveness of the PAPNET testing system in identifying
      false negative smears, using archival cervical cytologic smears from women with
      histologically proven diagnoses of high grade lesions and carcinoma of the
      uterine cervix. STUDY DESIGN: Forty-six negative smears from women who developed
      a high grade cervical intraepithelial lesion (CIN 3) or carcinoma of the uterine
      cervix within three years were retrieved from the archives, plus 20 consecutive
      control smears for each case. The smears were analyzed with the PAPNET testing
      system, and the selected cells were reviewed by a cytotechnologist using a strict
      protocol. RESULTS: With the PAPNET testing system, 9 of 46 (20%) smears were
      positive. Seven were reclassified as low grade and two reclassified as high grade
      squamous intraepithelial lesion (SIL). One of the 31 initially positive smears in
      the control group of 920 smears was not recognized as such. In the control group
      of 889 negative smears, 14 newly identified positive cases (1.6%) were detected,
      all low grade SIL. CONCLUSION: The PAPNET testing system is a good tool for
      detecting false negative smears and, when used as an adjunct to conventional
      screening, can reduce the false negative rate.

PMID- 9022730
TI  - Quality assurance in cervical cytology screening. Comparison of rapid rescreening
      and the PAPNET Testing System.
AB  - OBJECTIVE: To assess the performance of the PAPNET Testing System and compare the
      sensitivity of this automated device with that of rapid rescreening. STUDY
      DESIGN: In this study, 1,000 cervical smears previously diagnosed by our
      laboratory as negative were seeded with 20 particularly "difficult" cases. We
      submitted this seeded set of smears for rapid rescreening and to PAPNET to
      determine cases that could be detected by rapid rescreening, PAPNET or both.
      RESULTS: Rapid rescreening detected 9 of the 20 cases (45%). The PAPNET system
      identified 19/20 (95%). This investigation found PAPNET rescreening to be more
      effective than rapid rescreening in detecting the seeded difficult cases.
      CONCLUSION: Use of the PAPNET Testing System in tandem with rapid rescreening can
      reduce the rate of false negatives in diagnostically difficult cervical cytologic
      smears.

PMID- 9022731
TI  - Consistency of a double PAPNET scan of cervical smears.
AB  - OBJECTIVE: To determine the reproducibility and accuracy of the PAPNET system in
      finding and presenting abnormal and atypical cells. STUDY DESIGN: To assess the
      potential variation of a double PAPNET scan on the same cervical smear, 516
      cervical smears from women with abnormal histologic diagnoses were scanned twice
      via PAPNET and reviewed by two independent examiners in a double-blind trial.
      RESULTS: The false negative rate of 5.7% in conventional screening was reduced to
      0.4% and 0.8%, respectively, by PAPNET testing. The resulting concurrence of the
      first and the second PAPNET reviews was 99.2%, indicating the accuracy,
      sensitivity and consistency of this supplemental test. CONCLUSION: The results
      obtained demonstrate the reproducibility and accuracy of the system in finding
      and presenting abnormal and atypical cells.

PMID- 9022732
TI  - Simulation of primary cervical cancer screening by the PAPNET system in an
      unscreened, high-risk community.
AB  - OBJECTIVE: To evaluate the performance of the PAPNET system as a primary cervical
      cancer screening modality in an unscreened population with a high prevalence of
      cervical cancer and its precursor lesions. STUDY DESIGN: Consecutive cervical
      smears from 3,106 women, screened and reported in the usual manner, were
      submitted for analysis by the PAPNET system. The original manual screening
      diagnoses were compared with those obtained by PAPNET analysis. By inclusion of
      normal and abnormal smears, this evaluation not only provided quality assurance
      for the laboratory but also simulated primary screening by automation. RESULTS:
      Comparison of the two methods of screening showed statistically significant
      superiority of the PAPNET over conventional screening (89.6% vs. 63.8%,
      respectively) in low grade lesions, including atypical squamous and atypical
      glandular cells of uncertain significance (ASCUS and AGUS, respectively) and low
      grade squamous intraepithelial lesion. Conversely, there was no significant
      difference between PAPNET and manual detection (87.5% vs. 94.6%) for more
      significant abnormalities, including high grade squamous intraepithelial lesions
      and invasive carcinoma. CONCLUSION: The PAPNET system, which would probably not
      be affordable as a quality assurance modality only in the public health sector of
      this country, was shown to be more than sufficiently effective as a primary
      screening method for the large numbers of women likely to undergo cervical cancer
      screening in anticipated mass population programs.

PMID- 9022733
TI  - Clinical validation of interactive cytologic screening. Automating the search,
      not the interpretation.
AB  - OBJECTIVE: To evaluate the effectiveness of the PAPNET Testing System in
      improving cervical smear screening accuracy as measured during routine screening.
      STUDY DESIGN: A review of several recently published studies on the effectiveness
      of PAPNET testing in clinical use. System performance was retrospectively and
      prospectively evaluated and compared to the conventional method of testing. The
      use of PAPNET rescreening to identify smears having more significant
      abnormalities than had been initially diagnosed was investigated. RESULTS: New
      studies demonstrate that PAPNET testing increases the detection of significant
      lesions and improves cytotechnologist performance in routine clinical practice.
      Less variable diagnostic results are achieved with PAPNET testing as compared to
      conventional methods. The system is effective in identifying atypical smears
      having more serious abnormalities. CONCLUSION: When used as a supplemental method
      in routine practice, as studies have shown, PAPNET testing can reduce
      interobserver variability and increase the detection of abnormality.

PMID- 9022734
TI  - Laser scanning cytometry in pathology of solid tumors. A review.
AB  - OBJECTIVE: To review application of laser scanning cytometry (LSC) to analyze
      several different parameters of human solid tumors in relation to the cell cycle.
      STUDY DESIGN: Tissue sections of cytology specimens were stained for specific
      parameters and analyzed by LSC. RESULTS: Examples of LSC analysis of the
      expression of ER, Ki-67, cyclin B1, BrdUrd and ploidy are given. CONCLUSION: LSC
      provides rapid, high-precision measurement of the chosen parameters or
      constituents of each cell in a population of cells and correlates those
      measurements with the visual image of the corresponding cell.

PMID- 9022735
TI  - Multiparameter immunophenotypic analysis of fine needle aspiration biopsies and
      other hematologic specimens by laser scanning cytometry.
AB  - OBJECTIVE: To test the new laboratory technology of laser scanning cytometry with
      respect to immunophenotyping of all types of hematologic and lymphoreticular
      specimens and particularly those of limited size, such as fine needle aspiration
      biopsies and hypocellular body fluids. STUDY DESIGN: Over the course of two
      years, 343 hematologic and lymphoreticular specimens of all types were
      immunophenotyped by laser scanning cytometry using methodologies modified from
      those of conventional flow cytometric immunophenotyping. Results for all cases
      were corroborated with histology and/or cytology and, for some cases,
      immunohistochemistry and/or flow cytometric immunophenotyping. RESULTS: Over 98%
      of the 343 cases were successfully immunophenotyped by laser scanning cytometry.
      These included many hypocellular specimens, such as 38 fine needle aspiration
      biopsies and 33 body fluid specimens. CONCLUSION: Laser scanning cytometry is a
      new laboratory technology with several significant advantages relative to flow
      cytometry for immunophenotypic analysis of hematologic malignancy. The laboratory
      techniques are simplified, and antibody usage is reduced by 80%. Even more
      important, full-panel immunophenotyping with multiple antibodies can be performed
      on specimens as small as 50,000 cells total, making the technology particularly
      relevant to cytopathology. After immunophenotypic analysis, specimens can be
      stained for light microscopic examination, and individual cells meeting user
      defined antigenic or physical characteristics can be automatically relocalized.

PMID- 9022736
TI  - Slide-based laser scanning cytometry.
AB  - OBJECTIVE: To show that laser scanning cytometry (LSCM) can provide data
      equivalent to flow cytometry (FCM) data and furnish a number of benefits,
      including cell relocation for visualization and several additional measurement
      features that may make it more suitable than FCM for pathology laboratories.
      STUDY DESIGN: A laser scanning cytometer, the LSC, was developed. Several
      instruments, at sites in the United States and Japan during the last two years,
      provided data characterizing the instrument and its usefulness. RESULTS: Data
      describing the sensitivity, precision, accuracy, utility of added measurement
      features and cell relocation capabilities of the LSC are presented. The data
      illustrate the applicability of the LSC to multiparameter DNA ploidy studies,
      resolution of phases of the cell cycle and cytogenetics. CONCLUSION: Because it
      is microscope based and measures cells on a slide, not in a flow chamber; records
      the position of each cell on the slide; and has higher resolution, LSCM provides
      a number of benefits that may make it more suitable than FCM for pathology
      laboratories.

PMID- 9022737
TI  - Utility of the TracCell system in mapping Papanicolaou-stained cytologic
      material.
AB  - BACKGROUND: Much attention has been directed toward commercial application of
      automation technology to support both quality and productivity enhancement in
      cervical cytology screening. The introduction of a fully automated precision
      microscopy workstation, the AcCell Series 2000, (Accu-Med International, Inc.,
      Chicago, Illinois, U.S.A.) has made it possible to effectively incorporate
      automated prescreening systems that support the human screener. SYSTEM DESIGN:
      The TracCell 2000 slide mapping system (AccuMed) is a fully automated, stand
      alone prescreening device for Papani-colaou-stained cytologic material, such as
      cervical cytology specimens. The system locates the areas of the slide that do
      not require review and maps material in the remaining areas; it finds the optimal
      focal plane, calculates a preferred routing path for human review and determines
      speed adjustment relative to material density variation. Through slide bar coding
      identification, this information is transmitted to the AcCell precision
      microscopy workstation for presentation of the specimen to the human screener.
      DISCUSSION: By making it possible to automatically guide the human screener to
      the material of interest, the TracCell system eliminates the need to review empty
      space and irrelevant areas of the slide. This has the immediate advantage of
      improved productivity. In addition, by reducing the need to review neutral
      background material, the system increases the signal-to-noise ratio, thus
      contributing to a sustained level of vigilance in the screener. The system also
      addresses operator fatigue through computer-assisted focus and speed variation.
      This instrument is for investigational use only. The performance characteristics
      of the device have not been established.

PMID- 9022738
TI  - The AcCell series 2000 as a support system for training and evaluation in
      educational and clinical settings.
AB  - Providing effective training, retraining and evaluation programs, including
      proficiency testing programs, for cytoprofessionals is a challenge shared by many
      academic and clinical educators internationally. In cytopathology the quality of
      training has immediately transferable and critically important impacts on
      satisfactory performance in the clinical setting. Well-designed interactive
      computer-assisted instruction and testing programs have been shown to enhance
      initial learning and to reinforce factual and conceptual knowledge. Computer
      systems designed not only to promote diagnostic accuracy but to integrate and
      streamline work flow in clinical service settings are candidates for educational
      adaptation. The AcCell 2000 system, designed as a diagnostic screening support
      system, offers technology that is adaptable to educational needs during basic and
      in-service training as well as testing of screening proficiency in both locator
      and identification skills. We describe the considerations, approaches and
      applications of the AcCell 2000 system in education programs for both training
      and evaluation of gynecologic diagnostic screening proficiency.

PMID- 9022739
TI  - Using a CompuCyte Pathfinder to evaluate cytotechnology student diagnostic
      performance.
AB  - OBJECTIVE: To determine whether the Pathfinder Cytology System facilitates
      comparison of initial student diagnoses to rescreener diagnoses; provides a
      platform for collection, storage and retrieval of data on student screening
      performance; and generates a student screening "score." STUDY DESIGN: Using two
      CompuCyte Pathfinder units networked to a PC server and printer, eight
      cytotechnology students prescreened 1,224 gynecologic cases and entered their
      results into the Pathfinder database. Five staff cytotechnologists rescreened the
      cases and entered their diagnoses. The database containing the initial and
      rescreen diagnoses were transferred to a modified scoring grid that computed a
      screening "score" for each of the students. RESULTS: Student diagnoses matched
      cytotechnologist target diagnoses in 1,107 to 1,224 total cases (90.4%). Of these
      1,107 cases, 996 (81.3%) were reported as "within normal limits" (negative) by
      both student and cytotechnologist, and 111 (9.1%) were target diagnosed as
      abnormal (atypical squamous cells of undetermined significance [ASCUS] or above)
      by both student and cytotechnologist. Of 117 remaining cases, 112 (9.2%) were
      considered minor discrepancies (one-step discrepancy--e.g., benign cell change
      reactive vs. ASCUS--favor reactive), and 5 (0.4%) were considered significant
      discrepancies (two or more diagnostic categories of difference between student
      and cytotechnologist-within normal limits vs. low grade squamous intraepithelial
      lesion). The modified scoring grid developed by CompuCyte for this study was able
      to compute a numerical score for each student. CONCLUSION: Our preliminary
      assessment indicated that Pathfinder will facilitate evaluation of student
      performance. The system shows potential for eliminating the "paper trail" and
      manual dotting required for traditional student evaluation and, with the addition
      of a scoring program, may be standardized for use in both educational and
      clinical settings.

PMID- 9022740
TI  - Impact of the Pathfinder in a cytology laboratory.
AB  - OBJECTIVE: To assess the value of Pathfinder (CompuCyte, Cambridge,
      Massachusetts, U.S.A.) in improving adequacy and accuracy of screening and
      supporting quality control programs. STUDY DESIGN: The investigations were
      carried out on cervical cytologic smears only. Screening adequacy was assessed
      through the evaluation of percentage of slide coverage, percentage of overlapping
      and amount of elapsed time on smears screened with or without the Pathfinder by
      junior (426 cases) and senior (1,552 cases) screeners. Screening accuracy was
      investigated by comparing the performances of the same observer when reexamining,
      with the Pathfinder, a series of 1,051 cases already evaluated without the
      Pathfinder at least three months earlier. The review process was analyzed by both
      monitoring the elapsed time for relocation of manually or electronically marked
      cells (824 fields in 80 smears) and by comparing diagnostic discrepancies after
      the review of two series (74 + 74 cases) of randomly selected negative cases
      screened with or without Pathfinder. RESULTS: Pathfinder-assisted screening
      increased the number of cases with optimal slide coverage (> or = 90% of
      screenable area) and optimal overlapping (between 15% and 20%) by both junior (P
      < .00001 and P < .00001) and senior (P < .00001 and P < .0003) screeners. It also
      improved screening accuracy by decreasing the number of cases "unsatisfactory for
      evaluation" (P < .00001) (as a consequence of better coverage and overlapping)
      and the number of diagnostic discrepancies detected after review (P = .05).
      During the latter process, the time elapsed for relocation of electronically
      marked fields, as compared to manually marked ones, was greatly reduced (1 hour,
      25 minutes saved for revision of 40 smears). CONCLUSION: In these preliminary
      studies, the Pathfinder was a useful tool for both education and diagnosis
      (screening and review) in a cytology laboratory.

PMID- 9022741
TI  - Using the Pathfinder system to reduce missed abnormal cervical cytologic smear
      cases in a rescreening program.
AB  - OBJECTIVE: To evaluate the effect of Pathfinder (CompuCyte Corp., Cambridge,
      Massachusetts, U.S.A.), a process control instrument for microscopes used by
      cytotechnologists to monitor the mechanical aspects of their screening process,
      on the false negative cervical cytologic smear rate as detected in daily quality
      assurance rescreening. STUDY DESIGN: Pathfinder was put into routine use in a
      large cytology laboratory. After cytotechnologists were trained in its use, they
      monitored their time spent screening each slide, the area (percent) of the slide
      screened and the average percentage of overlap of fields of view. The number of
      abnormal cases missed in screening before and after the introduction of
      Pathfinder was determined by rescreening a random 10% of the "negative" cases.
      The evaluation took place over a nine-month period. RESULTS: A decrease in the
      number of missed abnormal cases was identified. The false negative rate for
      atypical cells of undetermined significance (ASCUS) fell from 37/2,336 (1.6%) to
      12/1,772 (0.7%), for a 56% decrease. The change in the number of squamous
      intraepithelial lesion cases, even over a nine-month period, was too small for
      comment. CONCLUSION: The effect of the continuous feedback and process
      standardization provided by the Pathfinder system was a decrease in the number of
      abnormal cases missed. This was due primarily to a marked decrease in the number
      of ASCUS cases missed. The Pathfinder provides a number of innovative management
      tools to ensure consistent high quality screening.

PMID- 9022742
TI  - Cellular fixation. A study of CytoRich Red and Cytospin Collection Fluid.
AB  - OBJECTIVE: To test a new fixative system (Roche Image Analysis System, Inc.
      [RIAS]) that may create a background free of blood and blood products, and to
      determine if the CytoRich Red system has a potential for automation of
      nongynecologic cytology. We compared the amount of red blood cells, background
      material and diagnostic ability in 40 bloody specimens prepared using the
      CytoRich Red system and our routine fixative, Cytospin Collection Fluid (Shandon,
      Inc.). STUDY DESIGN: Thirty bloody, nongynecologic specimens and 10 fresh FNA
      surgical specimens were prepared by adding specimen to equal volumes (10 mL) of
      CytoRich Red Fixative and Cytospin Collection Fluid. After initial
      centrifugation, the specimens were resuspended and cytocentrifuged using the
      Cytospin III (Shandon, Inc.) and the Hettich Universal cytocentrifuge. To test
      system dependency, specimens from each fixative were prepared using the alternate
      method of cytocentrifugation. Slides from both fixatives were stained,
      coverslipped and reviewed for the presence of red blood cells, background and
      diagnostic ability. RESULTS: Of the 40 CytoRich Red specimens, 92.5% (37) had
      little or no red blood cells as compared to 22.5% (9) of the 40 Cytospin
      Collection Fluid specimens. Seventy five percent (30) of the 40 CytoRich Red
      specimens showed reduction of background material in contrast to 15% (6) of the
      40 Cytospin Collection Fluid specimens. Diagnostic ability using CytoRich Red was
      enhanced by the reduction of red blood cells and background material. CytoRich
      Red performed equally as well with each cytocentrifugation device. CONCLUSION:
      CytoRich Red reduces red blood cells and background. Nuclear and cytoplasmic
      stain appear improved. This allows better evaluation of the cytologic features
      and interpretation of bloody specimens. It is non-system dependent and can be
      used with any method of preparation. Also, the reduction of background and blood
      lends itself to adaptation in the automation of nongynecologic cytology.

PMID- 9022743
TI  - Multiparameter absorption measurements in automated microscopy. Simultaneous
      quantitative determination of DNA and nuclear antigen.
AB  - OBJECTIVE: To test a dual DNA-nuclear antigen staining method for multiparameter
      absorption image analysis. STUDY DESIGN: MCF 7 cells, grown on glass slides,
      served as a model to test the staining technique. For DNA, Feulgen-based CAS
      quantitative DNA staining, and for nuclear antigen, alkaline phosphatase-based
      immunocytochemical staining with CAS Red as the chromogen, were used. MIB-1,
      estrogen and progesterone receptors were used as examples of nuclear antigen
      staining. Measurements were performed with the DISCOVERY image analyzer. RESULTS:
      Scatterplots, in which the nuclear antigen content was plotted against the DNA
      content, were obtained. Immunostain-positive and -negative populations could be
      discriminated. These cells were visualized in image galleries. The DNA histograms
      of the positive and negative cells showed no change in coefficient of variation
      or integrated optical density ratio of the G0, G1 and G2 + M peaks as compared to
      single DNA staining. The intensity of the immunostain increased as compared to
      the single immunostaining result. CONCLUSION: This staining technique allows the
      simultaneous accurate measurement of costained DNA and antigen within the same
      nucleus. This opens the possibility for studies in which nuclear antigen
      expression is monitored during the cell cycle or in cells of different ploidy
      classes. Identified cells can also be visualized by presentation in an image
      gallery or by relocation on the slide. This can support the analysis of clinical
      samples, where cytometric data can be correlated with and confirmed by visual
      diagnosis.

PMID- 9022744
TI  - Differential diagnosis of Hurthle cell neoplasms on fine needle aspirates. Can we
      do any better with morphometry?
AB  - OBJECTIVE: To determine the value of computerized interactive morphometry in the
      preoperative prediction of malignancy in fine needle aspirates of Hurthle cell
      neoplasms. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle
      aspiration smears of histologically proven Hurthle cell adenomas (HCA) (n = 10)
      and Hurthle cell carcinomas (HCC) (n = 9) were studied by interactive
      computerized morphometry. The measured features included the areas, perimeters
      and shape factors of individual cells, nuclei and nucleoli; the nucleocytoplasmic
      and nucleolonuclear ratios; and the eccentricities of nuclei and nucleoli.
      RESULTS: Only nucleolar features showed statistically significant differences
      between HCA and HCC. These features were the nucleolar area and its standard
      deviation, the nucleolar form factor and circularity, and the nucleolonuclear
      ratio. The most effective, albeit imperfect, discrimination was achieved by the
      nucleolar form factor. CONCLUSION: Nucleolar features, such as size, variation in
      size and roundness, may be more effective than cellular or nuclear features in
      differentiating between HCA and HCC in fine needle aspiration smears.

PMID- 9022745
TI  - Automated rescreening in cervical cytology. Mathematical models for evaluating
      overall process sensitivity, specificity and cost.
AB  - OBJECTIVE: To develop mathematical models to assist decision makers with the
      difficult task of evaluating the use of automated rescreening in the process of
      screening cervical smears. STUDY DESIGN: Using assumptions about incidence, per
      smear screening costs, and the sensitivity and specificity of cytotechnologists,
      pathologists and the rescreening device, basic probability models were developed
      to describe the overall sensitivity, specificity and cost of the screening
      process. RESULTS: The optimal screening policy is highly dependent on
      assumptions, and an automated system can significantly affect the overall system
      cost and accuracy. CONCLUSION: Mathematical planning models are valuable tools to
      assist decision makers in the design of a screening process for cervical smears.

PMID- 9022746
TI  - Dissecting the free energy of drug binding to DNA.
AB  - Advances in polyelectrolyte theory have provided a simple and straightforward
      basis for dissecting the free energy of ligand binding to DNA into its
      polyelectrolyte and non-electrostatic contributions. Experimental determination
      of the ligand-DNA binding constant as a function of monovalent salt concentration
      is required to provide the quantity (delta lnK(obs)/delta ln[MX]), from which
      delta Gpe may be calculated. delta Gpe is the contribution to the observed
      binding free energy from the polyelectrolyte effect. delta Gpe is entropic in
      origin, and results from the release of DNA-bound cations upon ligand binding.
      The non-electrostatic free energy contribution, delta Gt, is independent of salt
      concentration, and reflects the contribution of hydrogen bonding and hydrophobic
      and van der Waals interactions to the stability of the ligand-DNA complex. When
      comparing the affinity of different ligands for DNA, it is delta Gt that should
      be compared, since the effect of ligand charge may then be removed from
      consideration.

PMID- 9022747
TI  - Novel DNA-directed alkylating agents consisting of naphthalimide, nitrogen
      mustard and lexitropsin moieties: synthesis, DNA sequence specificity and
      biological evaluation.
AB  - Novel DNA-directed alkylating agents comprising naphthalimide, nitrogen mustard
      and lexitropsin moieties have been designed, synthesized and characterized. Their
      properties have been evaluated with respect to DNA binding ability, sequence
      preference, influence of flanking sequences on alkylation efficiency and
      cytotoxic potency against KB human nasopharangeal tumour cells. The results
      indicate that, in contrast to distamycin and bis-benzimidazole-bearing nitrogen
      mustard moieties where DNA alkylation is directed to adenine N3 sites in the
      minor groove, the naphthalimide nitrogen mustards alkylate DNA at accessible
      guanine N7 sites within the major groove. Structural factors that may affect
      cytotoxic efficacy are discussed.

PMID- 9022748
TI  - Synthesis, antiviral and antiproliferative activity of a new class of 5-(alkyl or
      arylthio)-6-vinyl uracils.
AB  - Uracil derivatives bearing substituted or unsubstituted vinyl groups at position
      C6 and alkyl- or arylthio groups at position C5 were synthesized and tested in
      vitro for antiviral and antiproliferative activity. None of the compounds were
      active against HIV-1. However, some of them inhibited the proliferation of
      leukemia, lymphoma and solid tumor-derived cell lines at micromolar
      concentrations. The maximum potency of antiproliferative activity correlates with
      the presence of unsubstituted vinyl groups and alkyl- or arylthio substituents.

PMID- 9022749
TI  - Molecular origins of selectivity in the interaction of amsacrine-4-carboxamide
      with GC-rich sequences in DNA.
AB  - To determine the molecular origins of the preferential binding of an antitumour
      amsacrine-4-carboxamide derivative to GC-rich sequences in DNA, we have used the
      polymerase chain reaction to synthesize a series of oligodeoxynucleotides in
      which the position of the purine 2-amino group is varied and then investigated
      the binding of the drug to normal and modified DNA molecules by means of DNase I
      footprinting. The results indicate that the 2-amino group of guanine represents
      an important but not unique element which directs selective binding of amsacrine
      4-carboxamides to GC-rich sequences.

PMID- 9022750
TI  - Prodrugs of thymidylate synthase inhibitors: potential for antibody directed
      enzyme prodrug therapy (ADEPT).
AB  - Prodrugs of quinazoline antifolate thymidylate synthase (TS) inhibitors have been
      designed and synthesized for use in antibody-directed enzyme prodrug therapy
      (ADEPT). The syntheses of the alpha-linked dipeptides of two potent thymidylate
      synthase inhibitors, ZD1694 [N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-
      ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid] and ICI198583 ?N-[4-[N-[(2
      methyl-3,4-dihydro-4-oxo-6-quinazolinyl) methyl]-N-prop-2-ynylamino]benzoyl]-L
      glutamic acid? are described. The alpha-carboxyl of the glutamic acid has been
      linked through an amide bond to an L-alanine or an L-glutamic acid. The alpha
      linked L-dipeptide prodrugs were designed to be activated to their corresponding
      thymidylate synthase inhibitors at a tumour site by prior administration of a
      monoclonal antibody conjugated to the enzyme carboxypeptidase A (CPA). The
      viability of a colorectal cell line was monitored with the potential prodrugs in
      the presence or absence of CPA or with the parent drugs alone. All the dipeptides
      had greatly decreased cytotoxicity, with a deactivation of approximately 100-fold
      for the ZD1694 prodrugs and approximately 20-200-fold for the ICI198583 prodrugs.
      Activation of the alpha-linked L-alanine dipeptides with CPA led to a
      cytotoxicity enhancement of approximately 10-100 fold.

PMID- 9022751
TI  - Macrophage recognition of LDL modified by levuglandin E2, an oxidation product of
      arachidonic acid.
AB  - Levuglandin (LG) E2, a secoprostanoic acid levulinaldehyde derivative, is a
      product of free radical oxidation that forms covalent adducts with lysyl residues
      on proteins. Treatment of LDL with LGE2 leads to uptake and degradation by mouse
      peritoneal macrophages. Oxidized LDL, but not acetyl LDL efficiently competed for
      binding and uptake of LGE2-modified 125I-LDL. This result suggests that LGE2
      modified LDL was recognized by a class of scavenger receptor that demonstrated
      ligand specificity for oxidized LDL but not for acetyl LDL.

PMID- 9022752
TI  - Covalent inhibition of digestive lipases: an in vitro study.

PMID- 9022754
TI  - Long-chain saturated fatty acids can be alpha-oxidised by a purified enzyme (M(r)
      240,000) in cucumber (Cucumis sativus).
AB  - An enzyme (M(r) 240,000) with high fatty acid alpha-oxidation activity has been
      purified from the fruit of cucumber (Cucumis sativus). The specific alpha
      oxidation activity in the purified fraction was 370 nmol/min per mg protein
      determined as liberation of 14CO2 from [1-14C]palmitic acid. alpha-Oxidation
      activity was observed both in the 12,000 x g pellet and 150,000 x g pellet by
      differential fractionation of cucumber homogenate. The enzyme was purified about
      220-fold to near homogeneity from a 12,000 x g fraction by solubilisation with
      Triton X-100R, ammonium sulphate precipitation, hydrophobic interaction and anion
      exchange chromatographies and Superose 12 gel filtration. The molecular mass of
      the native enzyme was 240,000, and the major subunit molecular mass of 40,000
      indicated an oligomeric structure.

PMID- 9022753
TI  - Epidermal growth factor enhances transcription of human arachidonate 12
      lipoxygenase in A431 cells.
AB  - Epidermal growth factor (EGF), determined by immunoprecipitation and Western blot
      analysis, increased both enzyme activity and protein level of 12-lipoxygenase in
      the solubilized microsomes of human epidermoid carcinoma A431 cells,
      respectively. The EGF-induced expression of 12-lipoxygenase mRNA was inhibited by
      transcription inhibitors such as actinomycin D and 5,6-dichlorobenzimidazole
      riboside. Promoters of different lengths for human 12-lipoxygenase gene were used
      to prepare the luciferase fusion vectors. These construct plasmids were
      transiently transfected into A431 cells, and the induction of luciferase
      expression by EGF was examined. A 4- to 6-fold increase in luciferase reporter
      activity stimulated by EGF for 18 h treatment was observed in plasmids with the
      5'-flanking region length of -951 bp and that of -224 bp upstream from
      translation starting site. The time-dependent induction of luciferase activity by
      EGF paralleled the EGF-induced enzyme activity and expression of 12-lipoxygenase
      protein. Taken together, the results of this study indicate that EGF enhanced the
      transcription of the human 12-lipoxygenase gene, resulting in an increase in the
      amount and activity of 12-lipoxygenase.

PMID- 9022755
TI  - Fatty acid unsaturation in the red alga Porphyridium cruentum. Is the methylene
      interrupted nature of polyunsaturated fatty acids an intrinsic property of the
      desaturases?
AB  - Polyunsaturated fatty acids (PUFAs) exogenously supplied to the red microalga
      Porphyridium cruentum were incorporated into cellular lipids. All the C18 PUFAs
      studied were desaturated by a delta 6-desaturase and all the C20 PUFAs by a delta
      5-desaturase. The latter enzyme desaturated even 20:2(11, 14) to 20:3(5, 11, 14)
      and 20:3(11, 14, 17) to 20:4(5, 11, 14, 17). We infer the existence of several
      fatty acid desaturases, with different chain length specificities. Furthermore,
      the introduction of double bonds in a methylene interrupted pattern, at least for
      alpha-type desaturase such as the delta 5- and delta 6-desaturases, is not an
      intrinsic property of the enzyme but a consequence of the arrangement of the pre
      existing double bonds in the fatty acid substrate.

PMID- 9022756
TI  - Differential inhibition of lipolysis by 2-bromopalmitic acid and 4-bromocrotonic
      acid in 3T3-L1 adipocytes.
AB  - Two inhibitors of fatty acid oxidation, 2-bromopalmitic acid (Br-C16) and 4
      bromocrotonic acid (Br-C4) were examined for their effect on lipolysis in 3T3-L1
      adipocytes. Both agents inhibited in a dose-dependent manner the rate of
      oxidation of exogenously added [1-14C]palmitate with similar time-courses,
      reaching a plateau at 3-9 h. While Br-C16 at 50 microM and 100 microM inhibited
      palmitate oxidation by approximately 40% and 60%, respectively, pretreatment with
      both concentrations inhibited lipolysis in washed cells in an almost identical
      manner. The magnitude of inhibition increased with time of pretreatment. On the
      other hand, like inhibition of fatty acid oxidation, inhibition of lipolysis by
      Br-C4 pretreatment was dose-dependent with maximal inhibition reached after 3 h
      pretreatment. The finding that isoproterenol- and dibutyryl cAMP-stimulated
      lipolysis were similarly suppressed by either Br-C4 or Br-C16 pretreatment,
      suggesting that a step distal to cAMP formation was involved. In addition, while
      the inhibitory effect of Br-C16 was not significantly influenced, the inhibition
      of lipolysis caused by Br-C4 was attenuated by pretreating cells with crotonic
      acid, octanoate, or palmitate. The longer chain-length of the fatty acids the
      cells were exposed, the stronger attenuation of the inhibition caused by Br-C4
      was observed. Moreover, whereas pretreatment with Br-C16 was without effect,
      pretreatment with Br-C4 significantly decreased hormone-sensitive lipase (HSL)
      activity in cell extracts, albeit to an extent much smaller than its inhibitory
      effect on lipolysis. In conclusion, these results indicate that irreversible
      inhibition of lipolysis by Br-C16 or Br-C4 cannot be attributed to their effect
      on fatty acid oxidation. Some factor capable of modulating HSL activity seems to
      be involved.

PMID- 9022757
TI  - Alterations of fatty acyl turnover in macrophage glycerolipids induced by
      stimulation. Evidence for enhanced recycling of arachidonic acid.
AB  - Glycerophospholipid biosynthesis by the de novo pathway was assessed in mouse
      peritoneal macrophages by pulse-labeling with [U-14C]glycerol.
      Phosphatidylcholine (PC), which amounts to about 35% of total cellular
      phospholipids, exhibited the highest rate of glycerol uptake, followed by
      phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Remodeling of PC
      molecular species by deacylation/reacylation was established by determining the
      redistribution of glycerol label over 2 h after a 1 h pulse of [U-14C]glycerol
      and by determining incorporation of 18O from H2(18)O-containing media. These data
      suggest that stearic and arachidonic acid enter PC primarily by the remodeling
      pathway but that small amounts of highly unsaturated molecular species, including
      1,2-diarachidonoyl PC, are rapidly synthesized de novo, and subsequently
      remodeled or degraded. Treatment of the cells with the ionophore A23187 resulted
      in the selective enhancement of arachidonate turnover in PC, PI and neutral
      lipid, as well as enhanced de novo PI synthesis. [U-14C]Glycerol labeling
      experiments suggest that arachidonic acid liberated by Ca(2+)-dependent
      phospholipase A2 activity is also reacylated in part through de novo glycerolipid
      biosynthesis, leading to the formation and remodeling of 1,2-diarachidonoyl PC
      and other highly polyunsaturated molecular species.

PMID- 9022758
TI  - Exogenous phosphatidic acid with saturated short-chain fatty acyl groups induces
      superoxide anion release from guinea pig peritoneal polymorphonuclear leukocytes
      by three different mechanisms.
AB  - Treatment of suspensions of guinea pig peritoneal polymorphonuclear leukocytes
      (PMN) with four species of phosphatidate (PA) containing short-chain fatty acids
      induced sustained superoxide anion (O2-) production after a lag time. The rank
      order of efficiency of these PAs in triggering O2- production was PA8:0 [1,2
      dioctanoyl-sn-glycerol-3-phosphate (GP)] > PA10:0 (1,2-didecanoyl-GP) > PA6:0
      (1,2-dicaproyl-GP) > > PA12:0 (1,2-dilauroyl-GP). The O2- release from PMN
      stimulated with PA10:0 or PA12:0, but not with PA6:0 or PA8:0, was lowered by the
      addition of 1 mM extracellular Ca2+. Studies with various inhibitors showed that
      the mechanism of multiphasic O2- production induced by PA8:0 depended on its
      concentration: 1 and 3 microM PA8:0 induced O2- production constantly after a lag
      time through a protein kinase-dependent mechanism that was inhibited by 100 nM
      staurosporine. With concentrations of PA of 10 microM or more, an additional
      mechanism that was independent of protein kinase became operative and predominant
      over the protein kinase-dependent one. This protein kinase-independent mechanism
      was inhibited selectively by 80 microM TMB-8. Concentrations of 30, 60 and 100
      microM PA first elicited transient O2- production via another protein kinase
      dependent mechanism that was more sensitive to H-7 than to staurosporine, and
      then sustained O2- production, mainly driven by the protein kinase-independent
      mechanism. Metabolism of exogenously added [14C]PA8:0 in intact PMN was examined
      in the presence and absence of propranolol. Results suggest that PA itself is
      more important rather than its degradation products such as diacylglycerol, in
      inducing O2- production via three different mechanisms described above.

PMID- 9022759
TI  - Induction of cyclooxygenase-1 in a human megakaryoblastic cell line (CMK)
      differentiated by phorbol ester.
AB  - Human megakaryoblastic cells (CMK line) are known to differentiate to mature
      megakaryocyte-like cells by treatment with 12-O-tetradecanoylphorbol 13-acetate
      (TPA). There are two isozymes of prostaglandin-forming cyclooxygenase enzyme.
      Constitutive cyclooxygenase-1 and inducible cyclooxygenase-2 were followed during
      differentiation of CMK cells. Treatment of the cells with 0.1 microM TPA for 4
      days resulted in a 5-20-fold increase in cyclooxygenase activity. Northern and
      Western blot analyses revealed that cyclooxygenase-1 mRNA and protein increased
      in parallel with the enzyme activity. In contrast, cyclooxygenase-2 mRNA was
      detected only at 3 h. Furthermore, most of the increased cyclooxygenase activity
      was immunoprecipitated with anti-cyclooxygenase-1 antibody, and was not affected
      by a cyclooxygenase-2-specific inhibitor, NS-398. These results indicated that
      cyclooxygenase-1 rather than cyclooxygenase-2 was predominantly induced depending
      on TPA. The enzyme thus induced was localized by immunoelectron microscopy in
      nuclear envelope and endoplasmic reticulum of the CMK cells.

PMID- 9022760
TI  - MR assessment of normal brain development in neonates and infants: comparative
      study of T1- and diffusion-weighted images.
AB  - PURPOSE: This study was designed to compare the sensitivity of T1- and diffusion
      weighted images for the assessment of brain maturation in human brains. METHODS:
      T1- and diffusion-weighted images were obtained in 32 children without
      neurological abnormalities or growth retardation. The ages at which signal
      intensity changes of white matter on T1-weighted images and diffusional
      anisotropy appeared were compared. RESULTS: In the optic radiation, diffusional
      anisotropy was observed in neonates < 1 month old, whereas signal intensity
      became high after 1 month old. In the frontal lobe, diffusional anisotropy began
      to appear after 1 month of age, but signal intensity became high after 6 months
      of age. These visual findings were confirmed statistically by quantitative
      analysis using signal intensity ratios and anisotropic ratios. Similar findings
      were observed in the external capsule and the genu of the corpus callosum.
      CONCLUSION: In conclusion, diffusional anisotropy is a sensitive indicator of
      brain maturation in neonates and infants and precedes signal intensity change on
      T1-weighted images.

PMID- 9022761
TI  - Application of magnetization transfer imaging for intracranial lesions of
      tuberous sclerosis.
AB  - PURPOSE: Our goal was to assess the effectiveness of magnetization transfer
      imaging (MTI) and the usefulness of the magnetization transfer ratio (MTR) in
      tuberous sclerosis (TS). METHOD: T2- and T1-weighted SE images with saturation
      pulse on/off before and after gadolinium enhancement in 10 patients with TS were
      obtained. The numbers of subependymal nodule (SEN), cortical tuber, and white
      matter (WM) abnormality detected on T1-, proton density, T2-, and MT T1-weighted
      SE images were compared. The contrast-to-noise ratio (C/N) on T1-, MT T1-, Gd T1
      , and Gd MT T1-weighted SE images and MTR (1-Msat/MO) on each set of
      saturation/nonsaturation images for each lesions were calculated. Mean MTRs
      (mMTRs) of WM and gray matter (GM) from seven normal volunteers were also
      obtained. RESULTS: MT T1-weighted SE images always depicted all lesions seen on
      conventional MRI and allowed depiction of more SENs (n = 80), cortical tubers (n
      = 197), and WM abnormalities (n = 82) than did T1-weighted (n = 58/85/33), proton
      density (n = 41/108/36), or T2-weighted (n = 48/121/46) SE images. The best C/N
      was obtained from Gd MT T1-weighted SE images in SENs and from MT T1-weighted SE
      images in other lesions. mMTRs of normal WM and GM were 36.43 and 29.42%,
      respectively. Cortical tubers and WM abnormalities had measured MTRs that were
      statistically equal to MTRs of GM in normal subjects (p < 0.005). MTRs of SENs
      showed lower mean (25.55%) and greater diversity (SD +/- 5.30), compared with
      MTRs of other lesions and normal GM and WM. One SEN with MTR of 20.72% was
      pathologically confirmed to be subependymal giant cell astrocytoma (SGCA). Nine
      SENs had measured MTR below 20.72% and six nodules among these were located in
      the region of the foramen of Monro, which is the characteristic location of SGCA.
      CONCLUSION: MTI may be effective in detecting all cranial lesions of TS. MTR may
      increase the specificity of MRI because it can differentiate the histopathologic
      subtypes and track and evolution of SEN into SGCA.

PMID- 9022763
TI  - Active hemorrhage of intracranial aneurysms: diagnosis by CT angiography.
AB  - Two cases of active hemorrhage from an intracranial aneurysm demonstrated by CT
      angiography are presented. In each case, extraluminal opacified blood was seen
      entering a recent hemorrhage surrounding the aneurysm, simulating a vascular
      structure. This is a potential pitfall in the interpretation of CT angiograms in
      patients with recent subarachnoid hemorrhage.

PMID- 9022762
TI  - Short-term CT and MR changes in brain tumors following 125I interstitial
      irradiation.
AB  - PURPOSE: The study was undertaken to assess characteristic short-term CT and MR
      changes in brain tumors following 125I interstitial irradiation. METHOD: Sixteen
      patients were included who had both CT and MR control examinations at regular
      intervals over a period of 18 months following treatment. Two groups were
      distinguished: low grade tumors (11 cases) and high grade malignancies (5
      patients). 125I seeds were used as temporary implants. The cumulative dose was 50
      60 Gy. RESULTS: In some patients of both groups, a low attenuation spheric
      structure with a contrast-medium-enhanced ring and a diameter of 6-8 mm was
      observed. There was no edema around the structure, which represents a zone of
      tissue necrosis at the site of the temporary 125I implant. Tumors in both groups
      were completely destroyed, some decreased in size, and others were unchanged.
      Pseudotumor necrosis with accompanying edema occurred in two patients with low
      grade astrocytoma, the diameter of which was > 4 cm. CONCLUSION: The behavior of
      cerebral tumors and their appearance on CT and MR images after interstitial
      irradiation seem to be variable. Decrease in tumor size may take place at
      different intervals after therapy. Brachytherapy of tumors with a diameter of > 4
      cm may produce space-occupying radionecrosis.

PMID- 9022764
TI  - Regional body FDG-PET in postoperative recurrent hyperparathyroidism.
AB  - PURPOSE: The use of preoperative imaging studies in patients with persistent or
      recurrent hyperparathyroidism after initial operation is generally accepted to
      improve the success rate and minimize the morbidity from reoperative surgery. The
      purpose of this study was to define the performance of FDG-PET for the
      localization of hyperfunctioning parathyroid tissue prior to reoperation. METHOD:
      Twenty patients with biochemical evidence of recurrent or persistent
      hyperparathyroidism following previous neck surgery were investigated. Regional
      body PET imaging of the neck and upper chest (axial field of view 27.5 cm) was
      acquired 45 min after 5-10 mCi FDG was given intravenously. RESULTS: Subsequent
      surgery revealed solitary parathyroid adenomas in 14 patients, seven hyperplastic
      glands in 2 patients, and parathyroid carcinoma in 1 patients. FDG-PET correctly
      identified 79% (11/14) of the parathyroid adenomas, 29% (2/7) of the hyperplastic
      glands, and the parathyroid carcinoma. FDG-PET was negative in 79% (30/38) of the
      surgically identified normal parathyroid glands. Eight false-positive findings
      led to a positive predictive value of 64%. CONCLUSION: These preliminary data
      suggest that regional body FDG-PET is a promising procedure in the evaluation of
      patients with persistent or recurrent postoperative hyperparathyroidism.

PMID- 9022765
TI  - CT findings of laryngeal tuberculosis: comparison to laryngeal carcinoma.
AB  - PURPOSE: Our goal was to describe the appearance of laryngeal tuberculosis using
      CT, with the intent of identifying features distinguishing laryngeal tuberculosis
      and carcinoma. METHOD: CT scans of 12 patients with laryngeal tuberculosis were
      analyzed retrospectively. Clinical symptoms, laryngoscopic exams, and presence of
      pulmonary tuberculosis on chest radiographs were also reviewed. RESULTS: In
      laryngeal tuberculosis, bilateral involvement was noted in nine patients (75%),
      while unilateral involvement was seen in three (25%). Diffuse thickening of the
      free margin of the epiglottis was a characteristic and frequent finding in
      tuberculosis (n = 6, 50%). No deep submucosal infiltration of the preepiglottic
      and paralaryngeal fat spaces was seen even when there was extensive involvement
      of the laryngeal mucosa. Cartilage destruction was not found in any case.
      CONCLUSION: Characteristic CT findings of laryngeal tuberculosis include
      bilateral involvement, thickening of the free margin of the epiglottis, and good
      preservation of the preepiglottic and paralaryngeal fat spaces even in the
      presence of extensive mucosal involvement. By comparison, laryngeal carcinoma
      presented unilateral involvement, infiltration of the preepiglottic and
      paralaryngeal fat spaces by a submucosal mass, cartilage destruction, and
      extralaryngeal invasion.

PMID- 9022766
TI  - Cerebral infarction after envenomation by viper.
AB  - A case of cerebral infarction after viper bite is described; the patient also had
      features of diffuse encephalopathy. Findings on MRI were suggestive of subacute
      hemorrhagic infarcts. Possible mechanisms for cerebral infarction in these
      circumstances were discussed. The mechanism of cerebral infarction in this case
      seemed to be vasospasm due to the action of the toxin, hemorrhagin, present in
      the venom.

PMID- 9022767
TI  - MRI of leptomeningeal melanocytosis in a patient with neurofibromatosis.

PMID- 9022768
TI  - Fibrous dysplasia of a parietal bone.

PMID- 9022769
TI  - CT of hemorrhagic complications of anticoagulant therapy.
AB  - Anticoagulant therapy is commonly used in patients at risk for, or known to have,
      thromboembolic disease. Although complications of therapy are uncommon in most
      patients, in others it may result in complications with substantial morbidity and
      occasionally may be life threatening. This essay reviews the role of
      anticoagulant therapy and defines the potential complications that may occur in
      the chest, abdomen, musculoskeletal system, and CNS. Specific pitfalls in
      diagnosis as well as complications of the bleeding process are discussed and
      illustrated. The role of CT scanning in the diagnosis and triage of these
      patients is clearly defined through select cases and clinical dilemmas.

PMID- 9022770
TI  - Combined hepatocellular and cholangiocarcinoma: correlation between CT findings
      and clinicopathological features.
AB  - PURPOSE: The purpose of this study was to clarify characteristics of combined
      hepatocellular and cholangiocarcinoma (HCC-CC) on CT and clinicopathological
      examinations. METHODS: Dynamic incremental CT was performed on 15 combined HCC-CC
      patients. CT of the early phase was started at 30 s and of the late phase at 120
      140 s, after the start of contrast medium injection at a rate of 3 ml/s. The
      images and clinicopathological findings were retrospectively compared. RESULTS:
      Lesions grossly resembling HCC (HCC type, n = 6) were well enhanced in the early
      phase and changed to low attenuation areas in the late phase. In lesions grossly
      resembling CC (CC type, n = 9), 8 of 9 lesions were enhanced only at the
      peripheral portions in the early phase and changed to low attenuation areas or
      had only central portions enhanced in the late phase. The other CC-type lesion
      was not enhanced in either the early or the late phase. In all 15 cases, there
      was no dilatation of the intrahepatic bile ducts. Hepatitis B virus surface
      antigen was positive in five cases. Hepatitis C virus antibody was positive in 10
      cases. Serum alpha-fetoprotein (AFP) levels were > or = 200 ng/ml in seven cases.
      CONCLUSION: In the CC type, enhanced CT images were compatible with CC, but
      positivities for virus markers and serum AFP levels were almost equivalent to
      those in HCC. Therefore, the CC type can be diagnosed as combined HCC-CC by
      evaluating virus markers and serum AFP levels with CT. In addition, no
      association of intrahepatic bile duct dilatation was considered to be a
      characteristic feature of combined HCC-CC.

PMID- 9022771
TI  - Intrahepatic cholangiocarcinoma: MRI and pathologic correlation in 14 patients.
AB  - PURPOSE: Our goal was to determine the MR features of intrahepatic
      cholangiocarcinoma and to correlate them with pathologic findings in a surgical
      series. METHOD: MRI in 14 patients with intrahepatic cholangiocarcinoma who had
      undergone resection was reviewed. All patients had T1- and T2-weighted SE
      sequences. Contrast-material-enhanced MRI was performed in 12 cases. Comparison
      between findings at MRI and pathologic examination was made. RESULTS: MRI
      depicted all the lesions but one satellite nodule of 2 cm diameter. All lesions
      were hypointense relative to the liver on T1-weighted images. On T2-weighted
      images, the tumors were predominantly isointense or slightly hyperintense
      relative to liver parenchyma in nine cases (64%) and were strongly hyperintense
      in five cases (36%). Central hypointense areas or bands were seen in eight cases.
      No capsule was detected. On contrast-enhanced MR studies, all lesions had
      progressive and concentric filling with contrast material. Associated findings
      such as vascular encasement, focal liver atrophy, or dilatation of intrahepatic
      bile ducts were observed in 10 cases (71%). Comparison with pathologic
      examination revealed that lesion signal intensity on T2-weighted MR images was
      due mostly to the amount of fibrosis, necrosis, and mucous secretion within the
      lesion. The nine isointense or slightly hyperintense lesions contained abundant
      fibrosis and had a low content of mucous secretion or necrosis, whereas the five
      hyperintense lesions contained low or moderate fibrosis and prominent mucous
      secretion and/or necrosis. CONCLUSION: Our study suggests that the MR features of
      intrahepatic cholangiocarcinoma are well correlated with pathologic findings, but
      are nonspecific. Associated findings may strengthen the diagnosis of intrahepatic
      cholangiocarcinoma at MRI.

PMID- 9022772
TI  - MRI for staging of gastric carcinoma: first results of an experimental
      prospective study.
AB  - PURPOSE: Our goal was to define the accuracy of MRI in the staging of gastric
      carcinomas. METHOD: Twenty consecutive surgical specimens were imaged immediately
      after gastrectomy for gastric carcinoma. Imaging was performed with a 1.0 T
      imaging system. T1-weighted, T2-weighted, and opposed phase images were acquired
      and analyzed for tumor infiltration of the gastric wall and the presence of
      perigastric lymph nodes. T and N stages were classified according to the
      International Union Against Cancer classification. Finally histopathologic
      staging of the specimens was compared with staging by MRI. RESULTS: In gastric
      specimens, three to five layers of the gastric walls were visible. There were
      typical signal intensity patterns on T1-weighted, T2-weighted, and opposed phase
      images. Tumor diagnosis and lymph node detection were best achieved by opposed
      phase imaging. Nineteen of 20 (95%) carcinomas were localized by MRI; T staging
      accuracy was 65%. The sensitivity to detect metastatic lymph nodes was 87%,
      specificity 60%. N staging accuracy (nodes positive versus negative) was 80%.
      CONCLUSION: High resolution MRI of gastric tumors is possible ex vivo. MRI
      enabled differentiation of up to five layers of the gastric wall, and therefore
      staging of gastric carcinomas is technically possible. However, to evaluate the
      exact role of MRI as a staging tool of gastric carcinomas, a correlation between
      MR morphology and the histologic structure of the gastric wall has to be achieved
      first.

PMID- 9022773
TI  - Efficacy of helical CT in T-staging of gastric cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the performance of helical CT
      in preoperative T-staging in patients with gastric cancer. METHOD: A total of 71
      patients with an established diagnosis of gastric cancer [75 lesions, 46 early
      (T1) and 29 advanced (T2 or more) cancers] were evaluated with helical CT.
      Helical CT was performed with 5-mm slice thickness at 5-mm/s table
      incrementation. Using the volumetric data by helical scanning, axial CT images (5
      mm slice thickness at 5-mm intervals) and multiplanar reconstruction (MPR) images
      were obtained. CT findings were compared with histopathologic studies of the
      resected specimen. RESULTS: Sensitivity of helical CT for gastric cancer was 26%
      (12 of 46) for early and 100% (29 of 29) for advanced cancer. Three lesions were
      misdiagnosed as gastric cancer by helical CT. Histopathologically, all early
      gastric cancers detected by helical CT were either polypoid or elevated types or
      showed massive invasion of the submucosal layer. The differentiation between T1
      cancer with massive submucosal invasion and advanced cancer was difficult. The
      differentiation between T2 and T3 cancer was possible in 73% (19 of 26) and
      between T1/T2 and T3/T4 (extraserosal invasion) in 83% (34 of 41). Overall T
      staging was correct in 66% (27 of 41). MPR images improved the detection rate
      (three lesions) or increased confidence in T-staging (eight lesions) over axial
      CT images. CONCLUSION: When helical CT detected gastric cancer that was not a
      polypoid or elevated type with underlying normal-appearing gastric wall, it was
      either T1 cancer with massive invasion of the cancer cells into the submucosal
      layer or advanced cancer. However, differentiation between these two stages was
      difficult on CT. Diagnosis of serosal invasion was not markedly improved by
      helical CT. MPR images increased confidence in the staging of certain gastric
      cancers, such as those in locations where CT images are susceptible to partial
      volume averaging effects.

PMID- 9022774
TI  - MR appearance and spectral features of injected ethanol in the liver: implication
      for fast MR-guided percutaneous ethanol injection therapy.
AB  - PURPOSE: Our goal was to evaluate several fast MR strategies for monitoring
      ethanol distributions so that percutaneous ethanol injection might be guided with
      MRI. METHOD: Fast RF spoiled GRE sequences (SPGR) and T2-weighted rapid
      acquisition with relaxation enhancement (RARE) sequences with and without
      spectroscopic-quality water suppression techniques were assessed for their
      ability to depict the distribution of injected ethanol in ex vivo pig liver. A
      line scan Carr-Purcell-Meiboom-Gill spectroscopic imaging sequence was used to
      validate observations and measure spectral relaxation characteristics of the
      ethanol signal in liver. Injected deuterated ethanol was also tested as an
      alternative possibility to depict the distribution of ethanol. RESULTS: The water
      suppressed T2-weighted RARE sequence depicted the distribution of ethanol better
      than other sequences. Deuterated ethanol appeared as a signal void on all
      sequences. CONCLUSION: Water-suppressed T2-weighted RARE sequences could be
      useful to rapidly monitor MR-guided PEI.

PMID- 9022776
TI  - MnDPDP as a negative hepatic contrast agent: evaluation of STIR imaging compared
      with T1-weighted SE and GE techniques.
AB  - Our goal was to assess the utility of manganese dipyridoxyl diphosphate (MnDPDP)
      as a negative hepatic contrast agent in short inversion time IR MRI (STIR).
      Twenty patients with focal liver lesions (15 with metastatic disease, 5 with
      hemangiomas) underwent MRI (T1-weighted SE, breath-hold GE, and STIR sequences)
      before and after infusion of MnDPDP (5 mumol/kg). We then compared the results
      obtained with each sequence for hepatic parenchymal enhancement, lesion-to-liver
      contrast-to-noise ratio (C/N) measurements, and the number of focal liver lesions
      observed in pre- and postcontrast images. Hepatic enhancement values of 25.3 +/-
      9.7 and 33.6 +/- 2.7% (mean +/- SEM) were obtained for the T1-weighted SE and GE
      sequences, respectively. The STIR sequence showed 78.9 +/- 2.1% negative
      enhancement (decrease of parenchymal signal intensity). Although a significant (p
      < 0.0001) C/N increase was seen after MnDPDP administration for all sequences,
      STIR showed the highest increase (149.0 +/- 25.5%) compared with T1-weighted SE
      (58.5 +/- 12.7%) and GE (83.3 +/- 7.2%) sequences. Similarly, more lesions for
      all sequences were detected, but again STIR showed the greatest postcontrast
      increase (29.0%). MnDPDP is an effective hepatic contrast agent. As both the
      negative hepatic enhancement and the increase in lesion-to-liver C/N were
      superior with the STIR sequence when compared with the positive enhancement and
      C/N values produced by the T1-weighted sequences, it should be considered for
      inclusion in the imaging protocol for patients with focal liver disease.

PMID- 9022777
TI  - Hepatic undifferentiated embryonal sarcoma: MR findings.
AB  - We report the MR findings of undifferentiated embryonal sarcoma of the liver. A
      15-year-old boy presented with a palpable mass in the right upper quadrant of the
      abdomen. A T1-weighted MR image showed a well defined hypointense mass with
      scattered high signal intensities in the left hepatic lobe. On T2-weighted
      imaging, the tumor changed to a hyperintense mass. Postcontrast T1-weighted
      imaging showed irregular enhancement of the solid portion of the mass. MR
      findings are correlated with those of angiography, US, CT, and pathology.

PMID- 9022775
TI  - Splenic parenchymal complications of pancreatitis: CT findings and natural
      history.
AB  - PURPOSE: Splenic parenchymal complications of pancreatitis are unusual and
      potentially life threatening. They usually require splenectomy in patients in
      poor condition. The present study describes natural history of splenic
      parenchymal complications and the role of CT scan in diagnosis and follow-up.
      METHOD: A retrospective study of 16 consecutive patients with splenic
      complications diagnosed by CT during staging of pancreatitis was performed. The
      presence and importance of splenic infarct, abscess, subcapsular collection, and
      hemoperitoneum were correlated with the patients' symptoms, type of management,
      and follow-up. RESULTS: No specific symptomatology was observed except in two
      cases of acute and massive hemoperitoneum. Fourteen infarcts, 11 subcapsular
      collections, 1 abscess, and 3 hemoperitoneums were observed. Four patients
      underwent splenectomy including two as an emergency for hemodynamic instability.
      Twelve patients were conservatively and successfully managed. CONCLUSION: Most
      splenic parenchymal complications of pancreatitis regress spontaneously and may
      be managed conservatively. Surgical indication is based mainly on clinical
      findings. CT is useful for detection and follow-up of these complications.

PMID- 9022778
TI  - Multiple mesenteric lymphatic cysts: an unusual feature of mesenteric
      panniculitis (sclerosing mesenteritis).

PMID- 9022779
TI  - Biliary infarct (Charcot-Gombault necrosis): CT and pathologic features.

PMID- 9022780
TI  - Sclerosing omentitis: CT demonstration.

PMID- 9022781
TI  - CT angiography: thoracic vascular imaging with interactive volume rendering
      technique.

PMID- 9022782
TI  - Localized benign fibrous tumors of the pleura: MR appearance.
AB  - PURPOSE: Our goal is to describe the MR findings in benign localized fibrous
      tumors of the pleura. METHOD: Chest radiographs, CT scans, and MR images of four
      patients with localized benign fibrous tumors of the pleura were retrospectively
      reviewed and correlated with the pathologic findings. RESULTS: Tumors ranged from
      4 to 18 cm in their largest diameter. Three tumors were located in the
      diaphragmatic region, and one was within the left major fissure. All tumors were
      round to ovoid, pedunculated, and well delineated. On T1-weighted SE MR images,
      tumors showed low signal intensity. All tumors had heterogeneous but
      predominantly low signal intensity on proton-density-weighted images and lower
      signal intensity on T2-weighted images. CONCLUSION: Localized benign fibrous
      tumors of the pleura were characterized by low signal intensity on all MR
      sequences that is explained by high collagen content within the tumors' stroma
      and should suggest the diagnosis preoperatively.

PMID- 9022783
TI  - Evaluation of coronary artery stenoses using electron-beam CT and multiplanar
      reformation.
AB  - PURPOSE: We assessed the diagnostic value of electron-beam CT with multiplanar
      reformation for coronary artery stenoses. METHOD: Thirty-seven patients who
      underwent conventional coronary angiography were evaluated with ECG-triggered
      thin section electron-beam CT with intravenous contrast enhancement. Multiplanar
      reformation of a stack of the images was performed to visualize coronary
      arteries. Two observers blind to the results of conventional coronary angiography
      independently evaluated the reformatted images. RESULTS: The sensitivity and
      specificity for the detection of significant lesions were 100 and 100% in the
      left main coronary artery, 83 and 84% in the left anterior descending artery, 67
      and 96% in left circumflex artery, 63 and 79% in the right coronary artery, and
      74 and 94% for total results, respectively. All false-positive results in the
      left anterior descending artery were caused by wall calcification, and in the
      right coronary artery, 83% of the false-positive results were caused by small
      slice gaps in noncalcified segments. CONCLUSION: Electron-beam CT was feasible
      for the detection of coronary artery stenoses. For interpretation of reformatted
      images, calcification and slice gaps should be taken into consideration.

PMID- 9022784
TI  - MRI of the breast in the differential diagnosis of mastitis versus inflammatory
      carcinoma and follow-up.
AB  - PURPOSE: Our goal was to evaluate the potential of dynamic MRI in differentiating
      mastitis and inflammatory breast carcinoma. Furthermore, we evaluated the
      potential of breast MRI to follow up mastitis patients under antibiotic
      treatment. METHOD: Twenty-one cases of dynamic breast MR (11 mastitis, 10
      inflammatory carcinomas) were reviewed. All patients had a history consistent
      with either mastitis or inflammatory breast carcinoma. The final diagnosis was
      histologically confirmed. RESULTS: Ninety percent of the inflammatory carcinomas
      were found to enhance > 100% in the first minute compared with 55% for mastitis.
      There is no significant difference between mastitis and inflammatory carcinoma.
      CONCLUSION: While breast MR cannot currently be used definitively to distinguish
      inflammatory carcinoma from mastitis, the differences in dynamic enhancement may
      prove to be useful in follow-up of presumed mastitis in problematic cases. If
      after biopsy the diagnosis remains unclear, breast MR may help to (a) demonstrate
      the success of the antibiotic treatment and (b) diagnose coexisting or
      confounding inflammatory carcinoma.

PMID- 9022785
TI  - Bronchioloalveolar carcinoma with widespread ground-glass shadow on CT in two
      cases.
AB  - Two cases of bronchioloalveolar carcinomas are presented. In both cases, chest CT
      demonstrated widespread ground-glass shadows. The findings on CT revealed tumor
      tissue character with tumor cell proliferation along the alveolar wall and air in
      the alveoli.

PMID- 9022786
TI  - Implementation and validation of a fully automatic system for intra- and
      interindividual registration of PET brain scans.
AB  - PURPOSE: Stereotactic coordinate spaces and methods to adapt subjects to that
      space are required when performing averaging of functional studies across
      subjects. METHODS: A rapid and fully automatic method to perform intersubject
      registration and adaptation to a previously defined coordinate space has been
      developed and implemented. The implementation has been performed within an
      existing software developed to facilitate manual registration and adaptation,
      thus offering a versatile combination of automatic and manual tools. Furthermore,
      a novel measure, based on the F-statistic for intersubject (block) differences,
      for the assessment of intersubject goodness of fit was suggested and validated.
      RESULTS: The intra- and intersubject registration was validated by its
      application to data from six human subjects participating in an activation study.
      The registration was performed both manually and automatically, and the results
      indicated that the automatic method performed at least as well as the manual. The
      block F-statistic was lower for the automatic method, and the z-scores were not
      significantly different for the methods. The localization of activated regions
      showed good agreement and differed by an average of 6 mm between the methods.
      CONCLUSION: It is concluded that the suggested method is a valuable alternative
      to the current manual approach.

PMID- 9022787
TI  - A new computer-assisted method for the quantification of enhancing lesions in
      multiple sclerosis.
AB  - PURPOSE: Our goal is to describe a new computerized method for the detection and
      quantification of enhanced multiple sclerosis (MS) lesions. METHOD: Gd-DTPA
      enhanced, thin section, T1-weighted images of seven patients (involving 336 slice
      images) with definite MS were analyzed using a new method based on the theory of
      "fuzzy connected components," developed and implemented on the 3DVIEWNIX software
      system. Four neuroradiologists selected "true" lesions from the computer-detected
      potential lesions with a yes/no response to the program query on 2 different
      days. The enhanced lesion volume and number of enhancing lesions for each image
      and each observer were subsequently computed. Additional studies involving 720
      slices were conducted to determine lesions that were missed by the system.
      RESULTS: The intra- and interobserver variability in the system was 0%. It took
      approximately 1 min of operator time per 3D study. The system output has no false
      positives and a mean false-negative volume of 1.3%. CONCLUSION: The novel system
      calculates enhancing lesion volume and the number of enhancing lesions with very
      little operator time, inter- and intraoperator variability, or false-positive and
      false-negative volumes. Computer-based quantification of enhancing lesion volume
      is an important objective measure of the activity of MS. The system is now in
      routine use in clinical investigations that study the role of enhancing lesions
      in the MS disease.

PMID- 9022788
TI  - The effect of helical CT on X-ray attenuation.
AB  - PURPOSE: Conventional CT has been shown to have wide variability in measured CT
      attenuation, both temporally within the same scanner and between different
      scanners. Many radiologists have raised the concern that the increased noise and
      multiple variables associated with helical CT may lead to degradation in
      resolution, specifically causing errors in CT number values. This study was
      designed to specifically evaluate the performance of both types of CT scanning in
      this regard. METHOD: A Picker PQ2000 helical CT scanner was used to scan a
      phantom containing multiple tissue-equivalent densities, allowing the measurement
      of CT attenuation of soft tissue, distilled water, cortical bone, medullary bone,
      air, and fat with a variety of techniques. A Catphan phantom was imaged with a
      variety of slice thicknesses (2, 4, and 8 mm), phantom positions (isocenter, y =
      +20 cm), and pitches (1.0, 1.5, 2.0) using both conventional and helical
      sequences. The entire image set was repeated with two additional annuli placed
      around the Catphan phantom to simulate the abdomen and the calvarium. The
      attenuation measurements of the same imaging parameters for helical versus
      conventional CT were statistically compared. RESULTS: No statistical differences
      were found for the CT numbers based on scan type (conventional versus helical)
      for all sequences and gantry positions tested, including helical CT with pitches
      > 1.0. Greater CT number variability was found with the extremes of tissue
      density such as with air and especially cortical bone, but were not statistically
      significant. The addition of the abdominal and calvarial annuli created a greater
      variation in CT attenuation values, but again were not statistically significant.
      CONCLUSION: The measurement of X-ray attenuation does not vary significantly with
      the use of the helical technique.

PMID- 9022789
TI  - A phantom study: evaluation of renal artery stenosis using helical CT and 3D
      reconstructions.
AB  - PURPOSE: We studied which set of CT parameters and modeling parameters yielded
      accurate measurements of three graded artificial renal artery stenoses. METHOD:
      An acrylic phantom resembling the abdominal aorta and renal arteries was
      constructed. Stenotic segments had diameters of 1.8, 3.2, and 4.8 mm; nonstenotic
      segment diameter was 6.3 mm. Helical scans were done using 1 and 3 mm collimation
      at pitches of 1, 1.5, and 2. 3D renderings were produced and measured.
      Multifactorial and regression tree analysis were used to determine the accuracy
      of the 3D renderings. Mean squared error (MSE) was used to compare true diameter
      with measured diameter. RESULTS: Collimation of 1 mm produced an MSE of 0.55
      versus an MSE of 1.35 for 3 mm collimation. Stenosis grade was the next most
      important parameter in the 1 mm subgroup and viewing direction in the 3 mm
      collimation subgroup. In the 1 mm subgroup, high and mid grade stenoses had an
      MSE of 0.52 versus low grade stenosis that had an MSE of 0.61. Pitch was a fourth
      order effect. CONCLUSION: Collimation of 1 mm combined with a pitch ratio as high
      as 2:1 is superior to 3 mm collimation. Shaded surface modeling was the single
      best choice for rendering 3D data. Stenosis grade interacted strongly with user
      controllable parameters.

PMID- 9022790
TI  - Multiplanar image reconstruction and 3D imaging using a musculoskeletal phantom:
      conventional versus helical CT.
AB  - PURPOSE: Our goal was to perform a detailed comparison of the relative
      performances of helical CT (pitches 1.0, 1.5, and 2.0) and conventional
      (overlapped and nonoverlapped) CT in detailed 3D and MPR musculoskeletal imaging.
      METHOD: A specially designed bone fragment phantom was imaged with multiple slice
      thicknesses using conventional (overlapped and nonoverlapped) and helical
      (varying pitch and slice index) CT. Studies were randomized, blinded, and graded
      using predetermined criteria by 10 radiologists. Statistical analysis included an
      assessment of raw image scores, a separate testing using duplicate copies of the
      conventional images as gold standards, and a multivariate model based upon the
      results of both scoring systems. RESULTS: When assessing raw scores of the
      images, conventional scans were consistently scored more favorably than helical
      studies. Decreasing the slice index improved conventional CT studies and helical
      studies with a pitch of 1.0, but showed no effect on helical studies with a pitch
      of > 1.0. When using the conventional studies as gold standards, the helical
      studies were consistently graded as poorer than conventional overlapped and
      nonoverlapped studies. CONCLUSION: For detailed musculoskeletal 3D and MPR work,
      helical CT may not adequately compare with conventional CT and offers no
      discernible advantage, particularly for pitches of > 1.0.

PMID- 9022791
TI  - Aunt Minnie's corner. Small bowel intussusception due to metastatic melanoma.

PMID- 9022792
TI  - Structure-based design of a new bisintercalating anthracycline antibiotic.
AB  - A new bisintercalating anthracycline antibiotic, WP631, has been designed and
      synthesized. The rational design of the new compound was based upon the geometry
      of monomeric anthracyclines bound to DNA oligonucleotides observed in high
      resolution crystal structures. Monomeric units of daunorubicin have been linked
      through their reactive 3' NH2 substituents on the daunosamine moieties to form
      the new bisanthracycline WP631. Viscosity studies confirmed that WP631 binds to
      DNA by bisintercalation. Differential scanning calorimetry and UV melting
      experiments were used to measure the ultratight binding of WP631 to DNA. The
      binding constant for the interaction of WP631 with herring sperm DNA was
      determined to be 2.7 x 10(11) M-1 at 20 degrees C. The large, favorable binding
      free energy of -15.3 kcal mol-1 was found to result from a large, negative
      enthalpic contribution of -30.2 kcal mol-1. A molecular model was generated that
      shows the favorable stereochemical fit of the linker in the DNA minor groove. The
      cytotoxicity of WP631 was compared to that of doxorubicin using MCF-7-sensitive
      and MCF-7/VP-16 MRP-mediated multidrug-resistant cell lines. These initial
      studies showed that while WP631 is slightly less cytotoxic than doxorubicin in
      the sensitive cell line, it appears to overcome MRP-mediated multidrug resistance
      and was much more cytotoxic against the MCF-7/VP-16 cell line than was
      doxorubicin. The design of new potential anticancer agents based on known
      structural principles was found to produce a compound with significantly
      increased DNA binding affinity and with interesting biological activity.

PMID- 9022793
TI  - Syntheses and structure-activity relationships of taxoids derived from 14 beta
      hydroxy-10-deacetylbaccatin III.
AB  - A series of new taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III was
      synthesized by means of the beta-lactam synthon method. Most of the new taxoids
      thus synthesized possess excellent cytotoxicity against human ovarian (A121), non
      small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines, and
      several of these taxoids show subnanomolar IC50 values which are severalfold to 1
      order of magnitude better than those of paclitaxel and docetaxel. Modifications
      at the 3'- and 3'-N-positions exert marked effects on the activity. For the
      substituents at C-3', the cytotoxicity decreases in the order 2-furyl
      approximately 2-methyl-1-propenyl > or = 2-methylpropyl > (E)-1-propenyl > or = n
      propyl > phenyl > > 2,2-dimethylpropyl. For the 3'-N substituents, the activity
      decreases in the order t-BuOCO > Ph > n-hexanoyl. A significant increase in the
      cytotoxicity against the doxorubicin-resistant human breast cancer cell line MCF7
      R that expresses the multidrug resistance (MDR) phenotype is observed by the
      proper modification of the substituent at C-10. The observed remarkable effects
      of the substituents at C-10 on the activity against MCF7-R can be ascribed to the
      effective inhibition of the binding of these new taxoids to P-glycoprotein that
      is responsible for MDR.

PMID- 9022794
TI  - Synthesis and structure-activity relationships of nonaromatic taxoids: effects of
      alkyl and alkenyl ester groups on cytotoxicity.
AB  - Several new nonaromatic taxoids are synthesized by means of the beta-lactam
      synthon method. These include taxoids modified with 3-methylbut-2-enoate, 3
      methylbutanoate, and cyclohexanecarboxylate groups in place of the benzoate at
      the C-2 position. In addition, taxoids with 2-methylprop-1-enyl, 2-methylpropyl,
      (E)-prop-1-enyl, and cyclohexyl groups at the C-3' position are also prepared in
      combination with the modifications at C-2. The alkyl and alkenyl ester groups at
      C-2 displayed pronounced effects on the in vitro cytotoxicity. Two of the fully
      aliphatic taxoids possess similar or stronger activity than paclitaxel and
      docetaxel. It is clear that the 2-benzoate does not play a unique role, and
      replacement with the appropriate alkyl and alkenyl groups provides taxoids with
      equivalent or superior activity.

PMID- 9022796
TI  - 5-HT1A-versus D2-receptor selectivity of flesinoxan and analogous N4-substituted
      N1-arylpiperazines.
AB  - We investigated the structural requirements for high 5-HT1A affinity of the
      agonist flesinoxan and its selectivity versus D2 receptors. For this purpose a
      series of arylpiperazine congeners of flesinoxan were synthesized and evaluated
      for their ability to displace [3H]-8-OH-DPAT and [3H]spiperone from their
      specific binding sites in rat frontal cortex homogenates and rat striatum,
      respectively. Variations were made in the N4-substituent and the arylpiperazine
      region. Effects of N4-substitution in the investigated compounds appeared to be
      quite similar for 5-HT1A- and D2-receptor affinity. Lipophilicity at a distance
      of four carbon atoms from the piperazine N4 atom seems to be the main
      contributing factor to affinity for both receptors. Our data show that the amide
      group in the flesinoxan N4-substituent is unlikely to interact with the 5-HT1A
      receptor but, instead, acts as a spacer. In contrast to the structure-affinity
      relationships (SARs) of the N4-substituents, selectivity for 5-HT1A versus D2
      receptors was gained by the arylpiperazine substitution pattern of flesinoxan.
      Restriction of flexibility of the N4-(benzoylamino)ethyl substituent and its
      effect on 5-HT1A-receptor affinity and activity were also studied. Our data show
      that in the bioactive conformation, the N4-[(p-fluorobenzoyl)amino]ethyl
      substituent is probably directed anti-periplanar relative to the HN4 atom. These
      results were used to dock flesinoxan (1) and two of its congeners (27 and 33)
      into a model of the 5-HT1A receptor that we previously reported. Amino acid
      residues surrounding the N4-[(p-fluorobenzoyl)amino]ethyl substituent of
      flesinoxan and its congeners are also present in D2 receptors. In contrast,
      several residues that contact the benzodioxane moiety differ from those in D2
      receptors. These observations from the 3D model agree with the 5-HT1A SAR data
      and probably account for the selectivity of flesinoxan versus D2 receptors.

PMID- 9022795
TI  - Analogues of N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine
      (PT523) modified in the side chain: synthesis and biological evaluation.
AB  - Four heretofore undescribed side chain analogues of N alpha-(4-amino-4
      deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine (PT523, 4) were synthesized via
      straightforward methods of antifolate chemistry, and their properties were
      compared with those of PT523 and two related compounds with the aim of defining
      the contribution of the hemiphthaloyl-L-ornithine moiety to the exceptional in
      vitro antitumor activity of this novel non-polyglutamatable aminopterin analogue.
      The IC50 values of N alpha-(4-amino-4-deoxypteroyl)-N beta-hemiphthaloyl-L-2,3
      diaminopropanoic acid (10) and N alpha-(4-amino-4-deoxypteroyl)-N gamma
      hemiphthaloyl-L-2,4- diaminobutanoic acid (9) against A549 human non-small-cell
      lung carcinoma cells in culture were 23 and 22 nM, whereas those of PT523 and N
      alpha-(4-amino-4-deoxypteroyl)-N epsilon-hemiphthaloyl-L-lysine (8) were 1.3 and
      5.2 nM. A decrease in the in vitro activities of 8 and 9 relative to PT523 was
      also observed against the panel of cell lines used by the National Cancer
      Institute to screen new drugs. However the potency of 8 and 9 remained several
      times greater than that of the historical control methotrexate against many of
      the cell lines in the screening panel. In an in vivo tumor model, SCC-VII murine
      squamous cell carcinoma, 9 and methotrexate were well tolerated as 5-day
      continuous infusions at doses of 0.52 and 0.75 mg/kg/day, whereas the highest
      tolerated dose of PT523 on this schedule was 0.19 mg/kg/day, in agreement with
      its lower IC50 in culture. To assess the importance of the hemiphthaloyl group in
      PT523, N alpha-(4-amino-4-deoxypteroyl)-N delta-isophthaloyl-L-ornithine (11), N
      alpha-(4-amino-4-deoxypteroyl)-N delta-terephthaloyl-L-ornithine (12), and N
      alpha-(4-amino-4-deoxypteroyl)-N delta-(4,5-dichlorohemiphthaloyl)-L-ornithine
      (13) were also synthesized. The IC50 values of 11 and 12 against A549 cells were
      45 and 3300 nM, as compared with 1.3 nM for PT523 and 23 nM for methotrexate. In
      a clonogenic assay against SCC25 human squamous cell carcinoma cells, the IC50
      values of 11 and 12 were 2.9 and 72 nM, as compared with 0.3 nM for PT523 and 27
      nM for methotrexate. Thus, activity was decreased by moving the aromatic carboxyl
      group in PT523 to the meta position and was further diminished by moving it to
      the para position. The IC50 of the halogenated analogue 13 against SCC25 human
      head and neck squamous carcinoma cells was 18 nM, suggesting lack of tolerance
      for this 4,5-disubstitution in the phthaloyl moiety. Our results suggest that the
      combination of a hemiphthaloyl group and three CH2 groups in the side chain are
      critical determinants of the potent in vitro activity of PT523.

PMID- 9022797
TI  - Nicotinamide derivatives as a new class of gastric H+/K(+)-ATPase inhibitors. 1.
      Synthesis and structure-activity relationships of N-substituted 2-(benzhydryl-
      and benzylsulfinyl)nicotinamides.
AB  - A new series of N-Substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides 7
      and 8 were synthesized. Upon acid activation in the acidic environment of the
      parietal cell, these compounds are converted into their active forms, 2,3-dihydro
      3-oxoisothiazolo[5,4-b]pyridines 5, which inhibit gastric H+/K(+)-ATPase.
      Inhibitory activities against [14C]aminopyrine accumulation stimulated by
      dibutyryl cAMP in isolated rabbit parietal cells in vitro and histamine-induced
      gastric acid secretion in pylorus-ligated rats by intraduodenal administration in
      vivo were evaluated, and the structure-activity relationships were examined.
      Among the compounds synthesized, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4
      pyridyl)nicotinamide (8b) showed potent inhibitory activities in vitro and in
      vivo equivalent to those of omeprazole, a typical H+/K(+)-ATPase inhibitor.
      Moreover, 8b was much more stable at neutral and weakly acidic pH than
      omeprazole, lansoprazole, and pantoprazole. Compound 8b is considered to be a
      promising agent for treating acid-related gastrointestinal disorders.

PMID- 9022798
TI  - Potent and selective non-benzodioxole-containing endothelin-A receptor
      antagonists.
AB  - The benzodioxole ((methylenedioxy)benzene) group is present in a number of
      endothelin (ET) receptor antagonists thus far reported. As part of our own
      endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N
      dibutylacetamido)-4-(1,3-benzodioxol-5- yl)-2-(4-methoxyphenyl)pyrrolidine-3
      carboxylic acid (A-127722). This is a potent antagonist, binding to the ETA and
      ETB receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and
      also contains the aforementioned benzodioxole. While this compound was seemingly
      optimized at its N-terminus, no effort had been directed toward understanding the
      contributions to binding affinity or receptor subtype selectivity conferred by
      the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists.
      Oxygenated benzenes, such as p-anisyl, were potent compounds with IC50s in the
      low-nanomolar range. Simple deletion of either of the two oxygen atoms
      (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar
      affinity for the ETA receptor. Additionally, the compounds showed enhanced
      selectivity, binding to the ETB receptor subtype in the micromolar range. This
      paper describes the development of this novel class of compounds.

PMID- 9022799
TI  - (3R)-N-(1-(tert-butylcarbonylmethyl)-2,3-dihydro-2-oxo-5-(2-pyridyl)-1H-1,4
      benzodiazepin-3-yl)-N'-(3-(methylamino)phenyl)urea (YF476): a potent and orally
      active gastrin/CCK-B antagonist.
AB  - A number of new 1,4-benzodiazepin-2-one-based gastrin/CCK-B receptor antagonists
      related to the archetypal analogue L-365,260, and more closely to the recently
      reported compound YM022, have been synthesized and evaluated for biological
      activity. The compounds were screened for their ability to inhibit the binding of
      [125I]CCK-8 to gastrin/CCK-B receptors prepared from rat brains and that of [3H]L
      364,718 to CCK-A receptors from rat pancreas, and were shown to be potent and
      selective ligands for the gastrin/CCK-B receptor. Functional studies in vivo
      demonstrated the compounds to be antagonists of the receptor as evidenced by
      their ability to inhibit pentagastrin-induced gastric acid secretion in
      anesthetized rats. More extensive evaluation in vivo included determination of
      ED50 values in the rat acid secretion model for selected compounds and an
      examination of the effect of these compounds on pentagastrin-induced gastric acid
      secretion in Heidenhain pouch dogs following oral and intravenous administration.
      Two compounds, i.e. (3R)-N-[1-[(tert-butylcarbonyl)methyl]-2,3-dihydro-2-oxo-5-(2
      pyri dyl) -1H-1,4-benzodiazepin-3-yl]-N'-[3-(methylamino)phenyl]urea, 15c
      (YF476), and (3R)-N-[1-[(tert-Butylcarbonyl)methyl]-2,3-dihydro-2-oxo-5- (2
      pyridyl)-1H-1,4-benzodiazepin-3-yl]-N'-[3-(dimethylamino)phenyl ]urea
      hydrochloride, 15d, showed potent dose-dependent effects in both models with the
      former showing excellent oral bioavailability and an ED50 of 21nmol/kg po in
      dogs. 15c is currently under clinical investigation for the treatment of gastro
      oesophagal reflux disease (GORD).

PMID- 9022800
TI  - Polyanion inhibitors of human immunodeficiency virus and other viruses. 5.
      Telomerized anionic surfactants derived from amino acids.
AB  - omega-Acryloyl anionic surfactants, whose polar heads are derived from amino
      acids, have been telomerized to prepare polyanions of a predetermined molecular
      weight. The main goal of this study was to verify whether the antiviral activity
      is influenced by the degree of polymerization of the polyanions. The oligomeric
      polyanions were evaluated for their activity against human immunodeficiency virus
      (HIV-1 or HIV-2) and various other RNA and DNA viruses. With regard to their anti
      HIV activity, a minimum number of anionic groups was necessary to achieve an
      inhibitory effect. Moreover, to be active the overall conformation of the
      polyanion must be such that the anionic groups are located on the external site
      of the molecule. With some of the polyanions, a 50% inhibition concentration
      (IC50) as low as 1 microgram/ mL, or even 0.1 microgram/mL, was noted against HIV
      1 in CEM-4 and MT-4 cells, respectively. The most potent polyanions also proved
      active against human cytomegalovirus and herpex simplex virus at concentrations
      of 5-10 and 20-40 micrograms/mL, respectively. No activity was observed against
      any of the other viruses tested (i.e., vesicular stomatitis, Sindbis, Semliki
      forest, parainfluenza, Junin, Tacaribe, Coxsackie, polio, reo, and vaccinia). No
      toxicity for the host cells was observed at concentrations up to 200
      micrograms/mL.

PMID- 9022801
TI  - Polyanion inhibitors of human immunodeficiency virus and other viruses. 6.
      Micelle-like anti-HIV polyanionic compounds based on a carbohydrate core.
AB  - A new class of polyanionic compounds, inhibitors of human immunodeficiency virus,
      was obtained from radical addition of mercapto acid or mercapto ester on a
      perallylated carbohydrate under UV irradiation with a catalytic amount of AIBN.
      Unlike the polyanions that we have previously prepared by polymerization
      reactions, the compounds are structurally well defined. Polyanions bearing 16
      carboxylate groups showed a 50% inhibitory concentration (IC50) of 0.1-4.1
      micrograms/mL against HIV-1 in MT-4 cells while not being toxic to the host cells
      at concentrations up to 125 micrograms/mL. The most potent polyanions also proved
      active against human cytomegalovirus at concentrations of 1-14 micrograms/mL. No
      activity was observed against any of the other viruses tested (i.e., herpes
      simplex virus, vesicular stomatitis virus, Sindbis, Semliki forest, parainfluenza
      3, Junin, Tacaribe, Coxsackie B4, polio-1, reo-1, or vaccinia virus).

PMID- 9022802
TI  - Cross-linking and sequence specific alkylation of DNA by aziridinyl quinones. 2.
      Structure requirements for sequence selectivity.
AB  - The cytotoxicities and DNA sequence selectivity for guanine-N7 alkylation of 22
      mono- and disubstituted 2,5-diaziridinyl-1,4-benzoquinones have been
      investigated. Several quinones produced patterns of alkylation following
      reduction with a selectivity for 5'-TGC-3' sequences. This sequence selectivity
      appeared to be dependent only on the presence of a hydrogen in position-6 of the
      quinone. A computer model, based on published crystallographic data, was used to
      explain this selectivity. The sequence selective quinones were generally more
      cytotoxic that the quinones which reacted randomly.

PMID- 9022803
TI  - Selectin-ligand interactions revealed by molecular dynamics simulation in
      solution.
AB  - Through a computer modeling and simulation technique, we investigated the binding
      mode of a complex of E-selectin-GSC-150, which is a novel selectin blocker. GSC
      150 is the 3'-sulfated Lewis X derivative with a long, branched alkyl chain.
      Initial attempts to construct a model for E-selectin-GSC-150 complex were
      performed based on a previously reported model of E-selectin-sialyl Lewis X
      (sLex) complex [Kogan, T.P.; Revelle, B.M.; Tapp, S.; Scott, D.; Beck, P.J.J.
      Biol. Chem. 1995, 270, 14047-14055]. In our model, the carbohydrate portion of
      GSC-150 interacted with the protein in a similar manner as that of sLex reported
      previously. Interestingly, each of the branched alkyl chains extended on the
      surface of E-selectin and interacted with two different hydrophobic portions. One
      of these hydrophobic portions consists of Tyr44, Pro46, and Tyr48. Another
      portion forms a shallow cavity, and it consists of Ala9, Leu114, and the alkyl
      moieties of the side chains of Lys111, Lys112, and Lys113. A subsequent 200-ps
      molecular dynamics simulation in solution revealed that the interactions involved
      in the sugar portion of the ligand were relatively weak, whereas the hydrophobic
      interactions involved in the branched alkyl chains were fairly stable in
      solution. These results suggest that the branched alkyl chain serves as an
      "anchor" for the tight binding of GSC-150 on the surface of E-Selectin. This is
      the first attempt to evaluate the dynamics of E-Selectin-ligand interactions in
      solution, and it sheds light on the nature of ligand recognition by selectins.

PMID- 9022804
TI  - Analogues of methotrexate in rheumatoid arthritis. 1. Effects of 10
      deazaaminopterin analogues on type II collagen-induced arthritis in mice.
AB  - Carbonation of the dianions (LDA) of 5-methylthiophene-2-carboxylic, 2
      methylpyridine-5-carboxylic, and 3-methylpyridine-6-carboxylic acids provided the
      respective carboxy heteroarylacetic acids. The crude diacids were directly
      esterified in MeOH-HCl to afford the diesters. Alkylation of the sodio anions
      with ethyl iodide yielded the appropriate alpha-ethyl diesters. The anions of the
      various diester substrates were then alkylated by 2,4-diamino-6-(bromomethyl)
      pteridine followed by ester saponification at room temperature to afford the
      respective 2,4-diamino-4-deoxy-10-carboxy-10-deazapteroic acids. The 10-carboxyl
      group was readily decarboxylated by heating in DMSO at temperatures of 110-135
      degrees C to give the diamino 10-deaza heteropteroic acid intermediates. Coupling
      with diethyl L-glutamate followed by ester hydrolysis afforded the target
      aminopterins. The analogues were evaluated for antiinflammatory effect in the
      mouse type II collagen model. The thiophene analogue of 10-ethyl-10
      deazaaminopterin was found to be an effective inhibitor in terms of reduced
      visual evidence of inflammation and swelling as determined by caliper
      measurement.

PMID- 9022805
TI  - Analogues of methotrexate in rheumatoid arthritis. 2. Effects of 5
      deazaaminopterin, 5,10-dideazaaminopterin, and analogues on type II collagen
      induced arthritis in mice.
AB  - Twenty-six compounds derived from the 5-deaza- and 5,10-dideazaaminopterin series
      of aminopterin analogues were evaluated for antiarthritic activity in the mouse
      type II collagen model. New compounds in the 5-deaza series were prepared by
      alkylation of an appropriate N-substituted (4-aminobenzoyl)-L-glutamic acid
      dialkyl ester or N-(5-amino-2-thenoyl)-L-glutamate diester with a 2,4-diamino-5
      alkyl-6-(bromomethyl)-5-deazapteridine. The resultant 5-deazaaminopterin diesters
      were saponified to provide the target 5-deaza analogues. 5,10-Dideazaaminopterins
      were synthesized by similar alkylation of the carbanions of appropriate 4
      carboxyphenylacetic, (5-carboxy-2-thienyl)acetic, or (5-carboxy-2-pyridyl)acetic
      acid dimethyl esters. The diesters of the 2,4-diamino-4-deoxy-10-carboxy-5,10
      dideazapteroic acid types so obtained were saponified and then readily
      decarboxylated by heating in Me2SO solution to provide the 2,4-diamino-5,10
      dideazapteroic acid-type intermediates. Peptide coupling with diethyl L-glutamate
      followed by ester hydrolysis at room temperature afforded the new 5,10
      dideazaaminopterin analogues. 5-Deazaaminopterins bearing an alkyl substituent at
      the 5-position were generally quite effective as antiinflammatory agents. Thus 5
      propyl-5-deazaaminopterin, 5-methyl-10-propargyl-5-deazaaminopterin, 5-methyl-10
      allyl-5-deazaaminopterin, 5-ethyl-5-deazamethotrexate, and 2,5-disubstituted
      thiophene analogue of 5-methyl-5-deazaaminopterin showed potencies greater than
      methotrexate by intraperitoneal or oral administration and were active over a
      considerably broader dose range. Useful activity in the 5,10-dideaza series was
      only observed for 5,10-dideazaaminopterin and its 10-methyl analogue. Alkyl
      substitution at C-5 or C-10 was generally detrimental to antiinflammatory
      activity in this series.

PMID- 9022806
TI  - Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT
      089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor
      ligand with cognition-enhancing properties.
AB  - 2-Methyl-3-(2(S)-pyrrolidinylmethoxy)pyridine, ABT-089 (S-4), a member of the 3
      pyridyl ether class of nicotinic acetylcholine receptor (nAChR) ligands, shows
      positive effects in rodent and primate models of cognitive enhancement and a
      rodent model of anxiolytic activity and possesses a reduced propensity to
      activate peripheral ganglionic type receptors. The profiles of S-4, its N-methyl
      analogue, and the corresponding enantiomers across several measures of
      cholinergic channel function in vitro and in vivo are presented, together with in
      vitro metabolism and in vivo bioavailability data. On the basis of its biological
      activities and favorable oral bioavailability, S-4 is an attractive candidate for
      further evaluation as a treatment for cognitive disorders.

PMID- 9022807
TI  - Correlation of constitutive activation of raf-1 with morphological transformation
      and abrogation of tyrosine phosphorylation of distinct sets of proteins in human
      squamous carcinoma cells.
AB  - We and others have reported an association between raf-1 protein serine/threonine
      kinase activity and transformation of mammalian cells. Because constitutive
      tyrosine phosphorylation of specific polypeptides is, in general, indicative of
      the transformed state of cells, we investigated the effect of activation of raf-1
      on phosphotyrosine-containing proteins in a human head and neck squamous cell
      carcinoma-derived cell line, PCI-06A. raf-1 expression and activity were
      modulated in PCI-06A cells by means of stable DNA transfection of either the
      entire coding domain of the human c-raf-1 cDNA (in the sense or antisense
      orientation) or a fragment of c-raf-1 cDNA coding for the kinase domain of raf-1.
      Our data showed that constitutive activation of raf-1 correlated with
      morphological transformation, whereas the inhibition of raf-1 expression and
      activity had no detectable effect on cell morphology as compared with the
      untransfected cells. Immunoprecipitation of whole-cell lysates with anti
      phosphotyrosine antibody followed by anti-phosphotyrosine immunoblotting revealed
      four phosphotyrosine-containing proteins of approximately 129, 120, 110, and 63
      kDa (I-IV, respectively) in the antisense c-raf-1 cDNA-transfected cells showing
      relatively diminished raf-1 activity but not in the transfectants expressing
      activated raf. We concluded that tyrosine phosphorylation of I-IV proteins is
      abrogated in PCI-06A squamous carcinoma cells transformed with constitutively
      active raf-1 protein kinase.

PMID- 9022808
TI  - Extended lifespan and immortalization of human fibroblasts induced by X-ray
      irradiation.
AB  - The induction of immortalization of human fibroblasts by carcinogens is a very
      rare process. Hybrids between immortal cells and normal fibroblasts senesce,
      indicating that immortal cells must lose one or more senescence genes for
      immortalization. To examine the possible involvement of multiple gene alterations
      in extended lifespan or immortalization of normal human fibroblasts, normal human
      fibroblasts (WHE-7 cells) and skin fibroblasts (MDAH 087 cells) derived from a Li
      Fraumeni syndrome patient with a mutated p53 allele were periodically irradiated
      with x rays. All six unirradiated control MDAH 087 cell cultures ceased growing
      by 37 population doublings (PD) and senesced. In contrast, one of six MDAH 087
      cultures irradiated one to three times with x rays (2 or 4 Gy at 2 Gy/min) grew
      continuously for over 450 PD, indicating that the cells were immortal. All 12 WHE
      7 cell cultures that were irradiated under the same conditions and all 20
      unirradiated control WHE-7 cultures did not become immortal. Single-stranded DNA
      conformation analysis and DNA sequencing revealed that no additional mutations
      were induced by x-ray irradiation in exons 2-10 of the p53 gene of the immortal
      cells (LCS-4X2 cells) and that loss of the wild-type p53 gene was necessary but
      not sufficient for immortalization. Karyotypic analysis and chromosome painting
      analysis demonstrated that a high percentage (more than 98%) of LCS-4X2 cells had
      lost chromosome 6. Irradiation of WHE-7 cells nine times with x rays (2 Gy at 2
      Gy/min) extended the cells' lifespans but did not immortalize them. These cells
      (X9 cells) exhibited a nonrandom karyotypic alteration, monosomy 6, that was
      confirmed by loss of heterozygosity for a polymorphic dinucleotide repeat
      sequence on chromosome 6. DNA analysis showed that X9 cells had no mutations in
      exons 2-10 of the p53 gene. DNA fingerprint analysis with a multi-locus probe
      detected DNA rearrangements in LCS-4X2 cells and X9 cells, indicating that both
      cells could have mutations at a gene or genes other than the p53 gene. The
      results are consistent with our previous findings that cells with a mutation in
      one gene involved in cellular senescence (i.e., the p53 gene in Li-Fraumeni
      fibroblasts) are prone to immortalization. Furthermore, we conclude that
      immortalization of normal human fibroblasts is a multistep process involving loss
      or inactivation of multiple genes, such as p53 and a gene on chromosome 6. Loss
      of a gene on chromosome 6 without p53 alterations extends cellular lifespan
      without immortalizing the cells.

PMID- 9022809
TI  - ASPB10 insulin induction of increased mitogenic responses and phenotypic changes
      in human breast epithelial cells: evidence for enhanced interactions with the
      insulin-like growth factor-I receptor.
AB  - The human insulin analogue ASPB10 has been reported to have increased affinity
      for the insulin receptor and to cause breast cancer in female rats. In the study
      reported here, we investigated whether ASPB10 has an increased mitogenic potency
      and induces a transformed phenotype in cultured human breast cells. In both MCF
      10 cells (a non-malignant human breast line) and MCF-7 cells (a human breast
      cancer cell line), ASPB10 was approximately twofold more potent than insulin in
      competing for 125I-insulin binding but sevenfold to tenfold more potent than
      insulin in competing for 125I-insulin-like growth factor (IGF)-I binding. In
      addition, ASPB10 was twofold more potent than insulin in stimulating insulin
      receptor autophosphorylation but significantly more potent in stimulating IGF-I
      receptor autophosphorylation in both cell lines. Moreover, ASPB10 was
      approximately sevenfold more potent than insulin in stimulating the growth of MCF
      10 and MCF-7 cells. This increased mitogenic effect of ASPB10 was significantly
      inhibited (but not abolished) when cells were cultured in the presence of alpha
      IR3, a monoclonal antibody to the IGF-I receptor. ASPB10, but not insulin, caused
      phenotypic changes (focus formation) in MCF-10 cells. Neither agent caused colony
      formation in soft agar in MCF-10 cells, but ASPB10 was more potent than insulin
      in stimulating colony formation in MCF-7 cells. These observations indicate that
      in human breast cells, ASPB10 has enhanced mitogenic effects and induces
      phenotypic changes as a consequence of its activation of both insulin and IGF-I
      receptors.

PMID- 9022810
TI  - Regulation of the transcription factor AP-1 in benign and malignant mouse
      keratinocyte cells.
AB  - The mouse benign keratinocyte cell line 308 was previously shown to have less AP
      1 DNA binding and transactivation ability than its malignant variant 10Gy5.
      Because elevated AP-1 activity in 10Gy5 appears to be critical for its malignant
      phenotype, we were interested in examining the molecular mechanisms that regulate
      activator protein 1 (AP-1) in this system. In both 308 and 10Gy5 cells, c-fos,
      fra-2, c-jun, jun B, and jun D were capable of binding to an AP-1 DNA binding
      site as determined by antibody clearance gel mobility shift assays. By western
      analysis, jun B steady-state nuclear and cytoplasmic protein levels were reduced
      in 10Gy5 cells as compared with 308 cells and jun B steady-state mRNA levels were
      similar in the two cell lines. The rate of jun B protein synthesis was decreased
      in 10Gy5 cells in comparison with 308 cells. Gel mobility shift experiments
      indicated that AP-1 inhibitory proteins were not present in the cytoplasm of 308
      cells. Oxidation-reduction posttranslational modification was not a major
      mechanism of AP-1 regulation in these cells as shown by 12-O-tetradecanoylphorbol
      13-acetate-responsive element (TRE) gel mobility shift assay of nuclear protein
      treated with a reducing agent and by western analysis for ref-1 protein. Overall
      phosphorylation of AP-1 proteins in 308 and 10Gy5 cells was examined by 32P
      orthophosphate labeling and immunoprecipitation. A difference in jun B protein
      overall phosphorylation was observed in the two cell lines. Our experiments
      suggest that decreased jun B protein levels may be a mechanism that results in
      elevated AP-1 activity in malignant 10Gy5 cells.

PMID- 9022811
TI  - Activation of AP-1 by okadaic acid in mouse keratinocytes associated with
      hyperphosphorylation of c-jun.
AB  - Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, is also
      a potent mouse skin tumor promoter. The effects of OA on regulation of c
      jun/activator protein-1 (AP-1) transcriptional activation were investigated in
      mouse keratinocytes. AP-1 DNA binding to the jun 12-O-tetradecanoylphorbol-13
      acetate-response element (TGACATCA) as determined by gel shift analysis was
      strongly induced by OA (100 ng/mL) at 6 and 12 h. Preincubation of nuclear
      extracts with anti-c-jun antibody demonstrated that c-jun was a major component
      of the DNA-bound AP-1 complex induced by OA in 308 cells. Transfection of a c-jun
      promoter-reporter construct demonstrated that AP-1 transactivation was induced by
      OA. The mRNA level of the c-jun proto-oncogene was dramatically increased by 6
      and 12 h of OA treatment. Furthermore, a significant induction of c-jun protein
      was stimulated by 6 and 12 h of OA treatment. Upon further analysis, it was found
      that OA induced a significant accumulation of Ser 73-phosphorylated c-jun protein
      in 308 cells. In summary, our data suggest that skin tumor promotion by OA is due
      at least in part to increased AP-1 DNA binding and transactivation mediated by c
      jun hyperphosphorylation.

PMID- 9022812
TI  - Definition by specific antisense oligonucleotides of a role for protein kinase C
      alpha in expression of differentiation markers in normal and neoplastic mouse
      epidermal keratinocytes.
AB  - Epidermal keratinocyte differentiation is a tightly regulated, stepwise process
      that requires protein kinase C (PKC) activation. Studies using cultured mouse
      keratinocytes induced to differentiate with Ca2+ have indirectly implicated the
      alpha isoform of PKC in upregulation of "late" (granular cell) epidermal
      differentiation markers. Activation of this isoform is also implicated in the
      suppression of "early" differentiation markers keratin (K) 1 and 10 that
      characterizes the neoplastic phenotype produced by the v-Ha-ras oncogene. We used
      antisense oligonucleotides (AS) to directly address the role of PKC alpha in
      regulating expression of these markers in normal and v-Ha-ras-transduced primary
      keratinocytes and a keratinocyte cell line (SP-1) containing an activating
      mutation of the c-Ha-ras gene. Transfection of PKC alpha AS reduced the PKC alpha
      protein level in a dose-dependent manner, with a maximum effect at doses of 100
      nM or higher. Immunoblot analysis with antibodies against PKC alpha, PKC delta,
      PKC epsilon, and PKC eta confirmed that PKC alpha AS selectively reduced the
      level of PKC alpha but not the other isoforms. In vitro kinase assays also
      revealed suppression of Ca(2+)-dependent PKC activity, which is the PKC alpha
      activity in this cell type, after transfection of PKC alpha AS. When PKC alpha AS
      treated normal keratinocytes were stimulated to terminally differentiate with
      Ca2+, induction of the late differentiation markers loricrin, filaggrin, and SPR
      1, as well as transglutaminase K mRNA, was suppressed when compared with their
      induction in scrambled AS-treated controls. In neoplastic v-Ha-ras-transduced
      keratinocytes and SP-1 cells, transfection of PKC alpha AS, but not the scrambled
      AS control, selectively downregulated PKC alpha and restored differentiation
      specific expression of K1. These findings directly confirm that PKC alpha is an
      important component of the signaling pathway regulating terminal differentiation
      of normal keratinocytes and that activation of PKC alpha contributes to the
      altered differentiation program of neoplastic murine keratinocytes.

PMID- 9022813
TI  - Characterization of the rat neurofibromatosis 2 gene and its involvement in
      asbestos-induced mesothelioma.
AB  - The neurofibromatosis 2 (NF2) tumor suppressor gene was recently implicated in
      the genesis of human mesothelioma. To investigate the role of this tumor
      suppressor gene in rat asbestos-induced mesothelioma, a commonly used model for
      the human disease, we characterized the rat homologue of NF2 and examined rat
      chrysotile-induced primary mesotheliomas and cell lines derived from chrysotile-
      and crocidolite-induced mesotheliomas for alterations in this gene. The coding
      sequence obtained for the rat NF2 gene had 90% nucleotide homology with the human
      NF2 gene. The rat NF2 gene was ubiquitously expressed as a 4.4-kb transcript in
      normal rat tissues as well as in rat mesothelioma cell lines. Reverse
      transcription-polymerase chain reaction analysis to examine splicing of NF2 exons
      in mesothelioma cells indicated that the exon splicing pattern was similar in
      normal and neoplastic cells. To determine if mutations had occurred in the NF2
      coding region in rat mesotheliomas, single-strand conformation polymorphism
      analysis and direct sequencing were used to screen 10 primary tumors and six
      tumor cell lines. No DNA sequence alterations were observed in any of the rat
      mesothelioma samples examined. These findings contrast with data reported
      previously for human mesotheliomas, in which the NF2 gene was found to be mutated
      in 40% of cases. Taken together, these data suggest that the role of NF2 in the
      development of rodent asbestos-induced mesothelioma may differ significantly from
      the role in the human disease.

PMID- 9022814
TI  - Development of postgraduate centres in the UK.

PMID- 9022815
TI  - The expanding role of ultrasound.

PMID- 9022817
TI  - Ovarian ultrasound.
AB  - Ovarian ultrasound is applicable to all ages, from the fetus through childhood
      and adolescence to the premenopausal and finally postmenopausal women.
      Indications include the chance finding of an ovarian lesion in the fetus, the
      diagnosis of ovarian pathology resulting in symptoms and the uses of follicle
      monitoring in infertility and screening for ovarian cancer in high-risk groups.

PMID- 9022816
TI  - Scrotal ultrasound.
AB  - Ultrasound is the most sensitive imaging method available for demonstration of
      the scrotal contents. The main indications for the use of ultrasound are scrotal
      masses and pain. Solid intratesticular masses are typically malignant, whereas
      solid epididymal masses are usually benign.

PMID- 9022818
TI  - Ultrasound of the neonatal brain.
AB  - Cranial ultrasound is currently the primary imaging modality employed in the
      assessment of the neonatal brain. Due to recent technological advances it is now
      possible to examine the developing cerebral surface, to assess sulcal-gyral
      maturation, and to investigate subtle changes in cerebral blood flow and
      parenchymal perfusion. This review discusses the currently accepted and the more
      controversial indications for neonatal transcranial ultrasound.

PMID- 9022819
TI  - Nuclear cardiology.

PMID- 9022820
TI  - Magnetic resonance imaging.

PMID- 9022821
TI  - Stress echocardiography.

PMID- 9022822
TI  - Continuous electrocardiographic monitoring.

PMID- 9022823
TI  - Sacrospinous vault fixation.

PMID- 9022824
TI  - Decision-making in surgery: the management of obstructive jaundice.

PMID- 9022825
TI  - Sevoflurane.
AB  - Sevoflurane is a new inhalational anaesthetic agent which can be administered via
      a conventional vapourizer. Its solubility allows rapid induction, control and
      emergence from anaesthesia. It may find a use in day case and paediatric
      anaesthesia. This article reviews the agent and discusses the relevant physical
      properties that make it suitable for this role.

PMID- 9022826
TI  - Safety among health-care workers in the NHS.
AB  - Within the health service one sometimes comes across the perception that the
      environment is by its very nature a safe environment. This is not necessarily so.
      The hospital environment contains man hazards, some of which may potentially be
      lethal, or cause disability or long-term ill health. This article looks at the
      importance of good health and safety in the health-care environment, and reviews
      the types of hazards and problems that might be present, and the legal
      requirements that apply.

PMID- 9022827
TI  - Molecular biology series 3. Tools of molecular biology: gene cloning.

PMID- 9022828
TI  - Cholesterol embolization after systemic streptokinase.

PMID- 9022829
TI  - G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases
      and arrestins.
AB  - G-protein-coupled receptors (GPCRs) represent a large family of proteins that
      transduce extracellular signals to the interior of cells. Signalling through
      these receptors rapidly desensitized primarily as the consequence of receptor
      phosphorylation, but receptor sequestration and downregulation can also
      contribute to this process. Two families of serine/threonine kinases, second
      messenger dependent protein kinases and receptor-specific G-protein-coupled
      receptor kinases (GRKs), phosphorylate GPCRs and thereby contribute to receptor
      desensitization. Receptor-specific phosphorylation of GPCRs promotes the binding
      of cytosolic proteins referred to as arrestins, which function to further
      uncouple GPCRs from their heterotrimeric G-proteins. To date, the GRK protein
      family consists of six members, which can be further classified into subgroups
      according to sequence homology and functional similarities. The arrestin protein
      family also comprises six members, which are subgrouped on the basis of sequence
      homology and tissue distribution. While the molecular mechanisms contributing to
      GPCR desensitization are fairly well characterized, little is known about the
      mechanism(s) by which GPCR responsiveness is reestablished, other than that
      receptor sequestration (internalization) might be involved. The goal of the
      present review is to overview current understanding of the regulation of GPCR
      responsiveness. In particular, we will review new evidence suggesting a
      pleiotropic role for GRKs and arrestins in the regulation of GPCR responsiveness.
      GRK-mediated phosphorylation and arrestin binding are not only involved in the
      functional uncoupling of GPCRs but they are also intimately involved in promoting
      GPCR sequestration and as such likely play an important role in mediating the
      subsequent resensitization of GPCRs.

PMID- 9022830
TI  - Antiplatelet effect of demethyldiisoeugenol.
AB  - A semisynthetic chemical compound, demethyldiisoeugenol, concentration
      dependently inhibited platelet aggregation and ATP release stimulated by thrombin
      (0.1 U/mL), platelet-activating factor (2 ng/mL), arachidonic acid (100 microM),
      collagen (10 micrograms/mL), and U46619 (1 microM) in rabbit washed platelets.
      The IC50 values of demethyldiisoeugenol on the inhibition of platelet aggregation
      induced by these five agonists were 157.3 +/- 22.3, 156.2 +/- 12.9, 53.6 +/- 4.7,
      54.5 +/- 3.9, and 87.7 +/- 3.2 microM, respectively. Demethyldiisoeugenol also
      inhibited thromboxane B2 formation induced by thrombin, platelet-activating
      factor, arachidonic acid, and collagen, and prostaglandin D2 formation was
      induced by arachidonic acid. The rising intracellular Ca2+ concentration
      stimulated by these five platelet aggregation inducers was inhibited by
      demethyldiisoeugenol, while formation of inositol monophosphate was unaffected.
      Platelet cAMP and cGMP levels were unchanged by demethyldiisoeugenol. It is
      concluded that demethyldiisoeugenol may directly inhibit both intracellular
      calcium mobilization and cyclooxygenase activity in platelets.

PMID- 9022831
TI  - Pharmacokinetic, angiographic, and histologic comparison of catheter-directed
      chemoembolization versus systemic chemotherapy in a canine model.
AB  - Chemotherapy with selective intraarterial embolization may promote sustained
      contact of the drug with the tumor and thus could be more effective in the
      treatment. In this phenomenon, pharmacokinetics of a drug such as mitomycin C
      (MMC) play a significant role in guiding the therapy. Therefore, we have compared
      the pharmacokinetics of MMC and assessed angiographic, morphologic, and
      histologic changes in the kidney following intravenous MMC versus renal artery
      infusion with and without embolization with embolic agents, Rhizoma Bletillae
      (RB) and Gelfoam (GF). Dogs randomly divided into four groups underwent selective
      infusion protocols. Blood samples from renal and common iliac veins were analyzed
      for MMC levels. Angiography and pathology were performed at 4 days. Intravenous
      MMC (IV-MMC) caused significantly lower renal vein MMC levels than intraarterial
      MMC (IA-MMC) and GF + MMC. RB + MMC produced the lowest MMC levels in both veins
      (p < 0.05). Common iliac MMC levels were not significantly different after IV
      MMC, IA-MMC, or GF + MMC. Angiographic and histologic studies showed extensive
      bleeding, necrosis, and vasculitis with thrombosis of the target kidneys after RB
      + MMC, GF + MMC, or IA-MMC, but not IV-MMC. Selective Rhizoma Bletillae
      chemoembolization can decrease systemic levels of MMC. Gelfoam does not provide
      sustained local release of MMC or decrease systemic levels of MMC compared with
      intravenous infusion. Selective renal MMC infusion without an effective embolic
      agent does not reduce systemic levels compared with intravenous delivery.

PMID- 9022832
TI  - Caco-2 cell disaccharidase activities are unaffected by gestational hormones.
AB  - We previously reported that lactose handling was significantly improved during
      late-phase pregnancy in women with a genetically determined adult-type
      hypolactasia. However, the adaptive mechanisms underlying the enhanced lactose
      digestion during pregnancy are not clear. Progesterone therapy has been
      associated in animals with increased intestinal lactase activity. To investigate
      the potential role of progesterone and estrogen as modulators of human lactase
      activity during pregnancy, we employed the human-derived intestinal epithelial
      Caco-2 cell line. Measurements of lactase and sucrase activities were performed
      in parallel with DNA content in progesterone- and estrogen-treated cells after 5,
      10, and 30 days of confluency. Caco-2 monolayer DNA content was observed to
      increase with duration of culture to an equivalent extent in both hormone-treated
      and control cultures. Lactase and sucrase activities were similarly unaltered by
      incubation with either progesterone or estrogen, at any time point tested. These
      data demonstrate that gestational hormones do not influence intestinal cell
      number nor disaccharidase activity in Caco-2 cells, at the doses tested. Although
      these studies were carried out in a malignant cell line, our data suggest that
      the improved lactose handling observed during pregnancy is probably related to
      prolonged intestinal transit.

PMID- 9022833
TI  - Verapamil blockade of the paradoxic bradycardia in rats induced by inferior vena
      cava occlusion during the administration of isoproterenol or calcium: the role of
      Ca2+.
AB  - It has been postulated that the vasodepressor reaction results from a vigorous
      ventricular contraction in the face of a reduced cardiac volume. Paradoxic
      bradycardia is a major manifestation of vasodepressor reactions. Allowing for the
      possible extrapolation between paradoxic bradycardia in rats and vasodepressor
      reactions, we examined calcium's role, an essential component of cardiac
      contraction, in the paradoxic bradycardia reaction. Paradoxic bradycardia was
      induced in rats by inferior vena cava occlusion during an isoproterenol infusion,
      and we examined calcium's role by studying whether verapamil inhibits and CaCl2
      causes paradoxic bradycardia, respectively. The maximum changes in R-R were
      measured during 60 s of inferior vena cava occlusion under the following
      conditions: (i) in control, the rate accelerated (R-R-21.8 +/- 2.4 ms (mean +/-
      SE), p < 0.001); (ii) during isoproterenol, paradoxic bradycardia occurred (R-R
      98.0 +/- 8.1 ms, p < 0.001), and this was inhibited by verapamil (R-R 5.0 +/- 2.1
      ms, p > 0.05) and restored by CaCl2 (R-R 109.3 +/- 6.5 ms, p < 0.001); (iii)
      during CaCl2 (without isoproterenol), paradoxic bradycardia also occurred (R-R
      82.1 +/- 22.9 ms, p < 0.001), and this was also inhibited by verapamil (R-R -18.5
      +/- 4.7 ms, p < 0.001). We conclude that verapamil inhibits the inferior vena
      cava occlusion induced paradoxic bradycardia caused by either isoproterenol or
      calcium, and these findings support the concept that increased cardiac
      contractile force triggers a vasodepressor reaction.

PMID- 9022834
TI  - Muscle aspartyl protease (cathepsin D) activity: detection using a chromophoric
      substrate and relation to wasting in DBA/2 mice implanted with leukemic L1210
      tumor cells.
AB  - The relationship between skeletal muscle aspartyl protease activity (APA) and
      wasting was investigated in male DBA/2 mice inoculated with L1210 tumor cells.
      Using the peptidic substrate H-Pro-Thr-Glu-Phe-Phe(NO2)-Arg-Leu-OH, which is
      specific for aspartyl proteases, proteases, proteolytic activity was detected in
      a number of tissues including muscle by using a crude extraction procedure for
      isolation of lysosomal enzymes. Biochemical characterization and increased muscle
      levels following either fasting or injection of endotoxin (ETX) suggest that the
      enzyme is likely cathepsin D. The wasting syndrome accompanying the tumor was
      measured by comparing the weight of the skinned hind limb in treated and control
      animals. DBA/2 mice inoculated intraperitoneally with L1210 cells developed
      multiple solid tumors in the peritoneum and ascites; maximal tumor burden was
      reached by 16 days. There was a significant reduction in hind limb weight (16 +/-
      2%; mean +/- SE) and significant increase (31 +/- 8%) in muscle APA associated
      with the development of ascites and solid tumors. Plasma APA activity was
      substantially increased (240 +/- 33%), while liver and spleen APA were increased
      (10-20%) but not significantly. Chronic pepstatin administration, 30 mg.kg-1.day
      1, for 7 days concurrent with the initiation of observable ascites and solid
      tumor formation (7 days post-inoculation), completely inhibited hind limb weight
      loss and alleviated the tumor-dependent increase of APA in both plasma and muscle
      without altering tumor development. Delaying the administration of pepstatin by 3
      days resulted in less of an inhibition (33 +/- 13%) of hind limb weight loss.
      Thus, cathepsin D or a similar aspartyl protease appears to be of key importance
      in the wasting syndrome associated with cachexia.

PMID- 9022835
TI  - Okadaic acid enhances prepulse facilitation of cardiac alpha 1-subunit but not
      endogenous calcium channel currents in Xenopus laevis oocytes.
AB  - Xenopus laevis oocytes can be selected to express relatively high levels of
      endogenous Ca currents. These currents are facilitated by prepulses. Facilitated
      endogenous Ca currents are unaffected by okadaic acid, RpcAMPS or the
      dihydropyridine (DHP) antagonist (+) PN 200-110. The endogenous currents and
      facilitation of endogenous currents by depolarizing prepulses are fully blocked
      by 1 mM Cd2+. In contrast, oocytes injected with mRNA encoding for the rabbit
      cardiac alpha 1-subunit express prepulse-facilitated Ca channel currents that are
      highly enhanced by the phosphoprotein phosphatase inhibitor okadaic acid (3-fold)
      and blocked by RpcAMPS and the DHP antagonist (+) PN 200-110. While okadaic acid
      selectively stimulates prepulse facilitation of cardiac alpha 1-subunit Ca
      currents, the DHP agonist (+) SDZ 202-791 largely increases (5-fold) both the
      control (before prepulse) and facilitated currents (after prepulse). (+) SDZ 202
      791 did not prevent the effect of RpcAMPS or okadaic acid on facilitation of
      cardiac alpha 1-subunit, suggesting that DHP stimulation is independent of
      phosphorylation leading to channel facilitation. The enhancement of prepulse
      facilitation of cardiac alpha 1L-subunit Ca channel current by okadaic acid can
      be accounted for by a speeding up in the rates of onset during the prepulse.
      Inhibition of phosphoprotein phosphatases by okadaic acid has only modest effects
      on the rates of recovery of cardiac alpha 1-subunit Ca channel current from
      facilitation in the time immediately following the prepulse.

PMID- 9022836
TI  - Effects of acute and long-term administration of prolactin on bone 45Ca uptake,
      calcium deposit, and calcium resorption in weaned, young, and mature rats.
AB  - The acute effect of prolactin on bone 45Ca uptake and the long-term effect on
      calcium turnover in femur, tibia, sternum, and lumbar vertebrae 5 and 6 were
      evaluated in weaned, young, and mature female Wistar rats. A dose-dependent
      increase in 45Ca uptake at 60 min after intraperitoneal administration of 0.01
      and 0.02 mg prolactin/100 g body weight was seen in femur of mature rats and in
      femur, tibia, and vertebrae of weaned rats. In contrast, bones of young rats were
      less responsive and responded only to the higher dose of prolactin. Daily
      subcutaneous injection of 0.25 mg prolactin/100 g body weight for 2 weeks in
      weaned rats enhanced calcium deposit in femur while increasing calcium resorption
      in all four bones. Young rats responded to prolactin only by enhancing calcium
      deposit in femur, tibia, and sternum. Mature rats, on the other hand, responded
      by increasing calcium resorption from all four bones while enhancing calcium
      deposit in femur, tibia, and sternum. It could be concluded that effects of
      prolactin varied with bone type and age of animals. Prolactin, in general,
      enhanced calcium turnover in both compact and trabecular bones of mature rats.
      Young rats responded to prolactin by increasing the rate of calcium deposit,
      whereas weaned rats increased calcium release. Nevertheless, all three age groups
      exhibited a net gain in calcium after 2 weeks of prolactin administration.

PMID- 9022837
TI  - Beta-adrenergic responsiveness of papillary muscles in the rat postinfarction
      model.
AB  - Rats in which ligation of the left anterior descending (LAD) coronary artery did
      not result in an infarct visible to the naked eye have generally been called sham
      operated controls and have been used to evaluate changes in the characteristics
      of the remaining viable myocardium of rats where myocardial infarction was
      present. Whether these sham-operated rats are equivalent to normal controls or
      whether they have been altered by the surgery is unknown. The purpose of this
      study was to evaluate potential differences in papillary muscle mechanical
      characteristics and responsiveness to beta-adrenergic stimulation in control,
      open-chest, sham-operated (aborted infarct), and infarct rats 4 weeks after
      surgery. Absence of significant myocardial damage was verified by morphologic
      examination in sham-operated hearts: myocardial infarction scar was 1.5 +/- 0.6%
      (mean +/- SE) of circumference, no infarct being transmural. Basal contractile
      indices were decreased in papillary muscles in infarct rats compared with the
      three other groups. The response in contractile indices of infarct muscles to
      isoproterenol was also less compared with the other three groups. However,
      although basal contractility was the same in muscles from sham-operated, open
      chest, and controls, the responsiveness of sham-operated muscles to isoproterenol
      was less: change in total tension of 2.9 +/- 1.2% vs. 9.5 +/- 2.7% for controls
      and 9.3 +/- 2.4% for open-chest (p < 0.05). Percent change in maximum rate of
      tension development (+dT/dt) was also less in muscles from sham-operated versus
      control muscles (21 +/- 2 vs. 33 +/- 6%; p < 0.05). Twitch configuration changed
      similarly with isoproterenol in all four groups. Thus, although contractility is
      unaffected by sham operation, beta-adrenergic responsiveness of tension
      generating indices is modified.

PMID- 9022838
TI  - Mechanism of the contractile effect of diaspirin-cross-linked hemoglobin in rat
      isolated aorta strip denuded of endothelium as revealed using an oil-immersion
      procedure.
AB  - Diaspirin-cross-linked hemoglobin (DCLHb) is a chemically modified hemoglobin
      (Hb) (i.e., alpha-subunits are cross-linked by a covalent bond) currently being
      tested as a potential oxygen-carrying blood substitute. It was examined for
      possible vasoactive properties, using the rat isolated aorta strip denuded of
      endothelium. In this experimental model, DCLHb (1.6-155 microM) was found to be
      inactive as a vasoconstrictor when added to the Krebs medium but to elicit
      contractile responses once the Krebs medium containing DCLHb was replaced by
      mineral oil, a procedure that favors the sequestration of a fixed amount of DCLHb
      within a substantially reduced volume of extracellular fluid. The contractile
      activity of DCLHb in our experimental model (i.e., prior exposure of tissues to
      drugs in the Krebs medium followed by replacement of the Krebs medium by mineral
      oil) was mimicked by methemoglobin and metmyoglobin, but not by cytochrome c,
      albumin, hemin, hematin, Fe2+, and a variety of hemorphins. It was abolished by
      indomethacin, SQ-29548 (prostaglandin H2-thromboxane A2 receptor antagonist),
      thiourea, or N-2-mercaptopropionylglycine (MCPG), reduced partially by verapamil,
      but not affected by dazmegrel, MK-886 (leukotriene biosynthesis inhibitor),
      dimethylsulfoxide, vitamin C or E, deferoxamine, NG-nitro-L-arginine, naloxone,
      and a variety of other drug receptor antagonists (e.g., prazosin) and protease
      inhibitors (e.g., pepstatin). Rat aorta strips denuded of endothelium exhibited
      contractile responses to arachidonic acid added in the Krebs medium (i.e., with
      no mineral oil added afterwards). Such contractile activity was reduced by SQ
      29548, thiourea, or MCPG. Addition of U-46619 (prostaglandin H2-thromboxane A2
      mimetic) to the Krebs medium also elicited contractile responses in rat aorta
      strips denuded of endothelium. Such contractile activity was reduced by SQ-29548,
      thiourea, or verapamil but not by MCPG. Within the limitations of our
      experimental approach, these results suggest that (1) the contractile activity of
      DCLHb in rat aorta strips denuded of endothelium following replacement of the
      Krebs medium by mineral oil involves the participation of a secondary mediator,
      which could be a vasoconstrictor metabolite of arachidonic acid; (2) the
      participation of reactive oxygen species, potential degradation products of DCLHb
      (e.g., heme, Fe2+, hemorphins), or other mediators in the contractile activity of
      DCLHb is unlikely; and (3) Ca2+ entry into target cells might be involved in the
      process by which DCLHb elicits its contractile activity in our experimental
      model.

PMID- 9022839
TI  - Twenty weeks of weight training increases lean tissue mass but not bone mineral
      mass or density in healthy, active young women.
AB  - Twenty young women (20.3 +/- 1.0 years) participated in a weight training program
      in which upper and lower body exercises were done twice per week for 20 weeks.
      Ten other women (20.2 +/- 0.4 years) served as a control group. Training resulted
      in significant (p < 0.05) increases in arm curl (73%), bench press (33%), and leg
      press (23%) lifting performance. Whole body (3.7%), trunk (3.0%), arm (9.7%), and
      leg (3.3%) lean tissue mass also increased significantly, based on measurements
      made by dual energy x-ray absorptiometry (DEXA). Changes in the control group
      were small and nonsignificant. In contrast, training did not increase DEXA
      measured bone mineral content (BMC) and density (BMD) in a whole body measure nor
      in arm, leg, ribs, thoracic and lumbar spine, and pelvis segments. Similarly, hip
      BMC and BMD at femoral neck, trochanter, intertrochanter, and Ward's triangle
      sites, and total hip did not increase with training. The data indicate that a
      resistance training program that effectively increases strength and lean tissue
      mass in young women may fail to increase BMC or BMD over a 20-week training
      period.

PMID- 9022840
TI  - The epidemiology and control of nematode parasites and Oestrus ovis in the winter
      rainfall area.

PMID- 9022843
TI  - Selected laboratory parameters of thoroughbreds.
AB  - Selected haematological, blood chemical and serological variables were
      investigated in healthy Thoroughbreds (n = 45) in training. Haemoglobin
      concentration, haematocrit, red, white and differential cell counts as well as
      serum concentrations of total and ionized calcium, sodium, potassium, chloride,
      urea, creatinine, total protein, albumin, inorganic phosphorus, total bilirubin,
      iron, glucose, magnesium, alkaline phosphatase, gamma-glutamyltransferase,
      lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine
      kinase were found to be within ranges previously reported for horses. No
      statistically significant difference was found between the haematocrit (Ht) of
      horses n = 44; mean = 0.44; SD = 0.02) of different performance or between those
      of different age groups. A significant difference was found between the Ht of
      males (mean = 0.43; SD = 0.02) and females (mean = 0.45; SD = 0.02) and between
      quiet (mean = 0.44; SD = 0.02) and excitable (mean = 0.46; SD = 0.02) horses. No
      significant difference in red cell potassium concentration was found between
      horses of different performance. Cortisol, insulin, parathormone (C-terminal),
      aldosterone and folate concentrations respectively varied between 89-204 (mean =
      144.4; SD = 25.47) nmol l-1, 4.2-23 (mean = 10; SD = 4.30) m U l-1, 65.2-91.4
      (mean = 79.46; SD = 9.34) pmol l-1, less than 138 to 379 pmol l-1 and 9.4-21.5
      (mean 14.5; SD = 2.87) nmol l-1. Vit B12 concentrations exceeded 1400 pmol l-1.
      Blood lead concentrations in all animals were below 15 ug l-1. Fifteen (33.3%) of
      the horses were carriers of babesiosis. Laboratory findings concerning these
      horses did not differ from those of the other horses.

PMID- 9022842
TI  - The bent-leg syndrome in sheep. II. Association with genetic markers.
AB  - Comprehensive blood typing (17 factors) and electrophoretic protein markers
      (haemoglobins, transferrins and albumins) were determined on S.A. Mutton Merino
      sheep (n = 275). The frequencies of these genetic markers were compared between
      ram lambs with normal and ram lambs with bent-legs and in a second trial between
      non-affected ewes and their lambs and ewes and lambs which were considered to be
      carriers of genetic factors resulting in the bent-leg syndrome. The presence of
      blood factors 2, 3 and 13 and the absence of factors 8, 10 and 17 is possibly
      linked to the bent-leg syndrome. Although the frequencies of TFA and TFD alleles
      were higher in the suspected carrier animals than non-affected animals, no
      definite linkage to the bent-leg syndrome was found. Haemoglobin and albumin type
      showed no correlation with the bent-let syndrome.

PMID- 9022844
TI  - Overberg Research Projects. VII. Anthelmintic sales in the Swellendam area of the
      southern Cape.
AB  - In the Swellendam area, benzimidazoles held 34.5% of the market for sheep and
      goat nematocides in 1988, ivermectin 30.1%, levamisole 13.7%, combination
      products 13.5%, salicylanilides 6.8% and morantel 1.4%, while products containing
      benzimidazole accounted for 48.1% of sheep and goat nematocide sales. The sheep
      and goat nematocide and cestocide markets in the Swellendam area totalled
      1,386,280 and 94,080 therapeutic doses respectively, costing R448 887,10 and R79
      242,02, while the cattle anthelmintic market totalled 12,209 therapeutic doses,
      costing R30 520,22. A mean of 3.45 therapeutic doses of nematocide were purchased
      for sheep and goats during 1988 at a per capita cost of R1.12 at December 1988
      prices. Furthermore, the mean per capita expenditure on anthelmintics against
      both the nematodes and cestodes of these animals, amounted to R1.31. Nematocides
      used for sheep and goats in this market segment, cost 36 cents per dose. The mean
      escalation of anthelmintic prices between January and December 1988 was 10%,
      ranging from -6 to 30%.

PMID- 9022846
TI  - Serological studies of bovine respiratory syncytial virus in feedlot cattle in
      South Africa.
AB  - Serum antibody titres to bovine respiratory syncytial virus were determined in
      cattle (n = 282). Samples were obtained at various feedlots and were collected in
      the 1989 and 1990 winter seasons, during the course of investigations into
      outbreaks of respiratory tract infections in feedlot cattle. Results of the
      survey revealed an antibody prevalence of 43% to bovine respiratory syncytial
      virus. Titres ranged from 1:10 to 1:1280 as determined by the indirect
      fluorescent antibody test. The results also indicate that bovine respiratory
      syncytial virus is probably widespread in feedlot cattle in South Africa, and
      that this virus may be a contributing factor in the bovine respiratory complex.

PMID- 9022845
TI  - Overberg Research Projects. VIII. The productivity of Merino ewes subjected to
      different internal parasite control programmes in the winter rainfall region of
      South Africa.
AB  - Suckling Merino lambs on lucerne pasture, demonstrated no appreciable mass gain
      when compared with untreated controls, despite regular treatment with
      anthelmintics. This was ascribed to severe parasitic challenge. After weaning and
      transfer to wheat stubble fields with no parasitic challenge, however, the live
      mass of the untreated lambs, still harbouring a residual burden of nematodes, was
      depressed. Control sheep produced 1.2 kg less wool than regularly-treated sheep,
      but produced finer wool which had a higher market value. Regularly-treated ewes
      (F1) produced 12.1% more lambs, but their mean live mass was 2.6 kg lower than
      that of ewes treated less frequently. The overall financial benefit was in favour
      of the group which received fewer anthelmintic treatments and was due mainly to
      the higher market value of the finer wool produced by these apparently stressed
      animals.

PMID- 9022847
TI  - Septicaemic Erysipelothrix rhusiopathiae infection in the Little Swift (Apus
      affinis).
AB  - Erysipelothrix rhusiopathiae was found to be the causal organism of high
      mortality in a colony of Little Swifts (Apus affinis (Gray), occupying the
      vertical walls of high-rise buildings. The mortality continued for a period of
      about 4 weeks. Negative post-mortem findings necessitated a diagnosis based on
      bacterial examination during which the causal organism was isolated in pure
      culture from the liver, spleen and heart blood of affected birds.

PMID- 9022848
TI  - Serological survey for bovine leptospirosis in the Volksrust district.
AB  - Serum samples (n = 860) from cattle in the Volksrust district were tested for
      Leptospira antibody titres. Seventeen (2%) of the animals were positive for
      leptospirosis, while 9(1%) animals showed suspect reactions. Titres against L.
      hardjo, L. pomona, and L. tarassovi were the most prevalent.

PMID- 9022849
TI  - Survey for antibodies to selected viruses in laboratory mice in South Africa.
AB  - Serum samples (n = 184) from 3 conventional laboratory mouse colonies were tested
      for antibodies with an indirect fluorescent antibody (IFA) test to Theiler's
      murine encephalomyelitis virus (TMEV), encephalomyocarditis virus (EMCV), and
      reovirus Type 3. The percentage of mice with antibodies to reovirus Type 3, were
      comparable in all 3 groups, namely 40, 46 and 60%. Antibodies to TMEV showed the
      greatest variation, namely 0, 10 and 31%, whereas antibodies to EMCV were
      confirmed in only one colony (7%). In addition, 98 serum samples from 2 other
      colonies yielded 69% animals positive for rotavirus with the IFA test.

PMID- 9022850
TI  - Effect of a growth promoter on preweaning growth of beef steer calves.
AB  - The influence of a growth promoter on preweaning growth of beef steer calves in
      the Kalahari thornveld and shrub bushveld was investigated. Calves (n = 40)
      implanted with a testosterone propionate-oestradiolbenzoate compound at an
      average age of 120 d, attained a higher (P < 0,005) weaning mass (256,7 vs 239,1
      kg) and superior gains (93,9 vs 79,9 kg) over the trial period than the control
      group (n = 40).

PMID- 9022851
TI  - Lead poisoning in a dog.
AB  - A case of lead poisoning caused by ingestion of a lead roof-washer is described
      in a one-year-old, spayed Fox Terrier bitch, presented with nervous signs, and
      basophilic stippling of red blood cells. Blood concentrations of lead were in the
      low toxic range. Radiography of the abdomen revealed radio-dense objects in the
      stomach, which on gastrotomy included a lead roof-washer. Prior to removal of the
      foreign bodies, the dog showed remarkable improvement on non-specific symptomatic
      treatment alone, and recovered well after surgery, only to die unexpectedly
      several hours later. Concentrations of lead in the liver and kidneys were
      extremely high, and histology revealed typical intracellular inclusions and organ
      degeneration. In the light of these findings, it is suggested that all cases of
      suspected or confirmed lead poisoning be given specific chelation therapy.

PMID- 9022852
TI  - Polycythaemia vera in a dog.
AB  - An 8-month-old Dachshund showed signs of severe depression and intermittent, mild
      generalised seizures. A diagnosis of polycythaemia vera was made and the clinical
      signs ascribed to the hyperviscosity associated with this condition. Treatment by
      phlebotomy was initiated before the dog died.

PMID- 9022853
TI  - Gold Medal of the SAVA: 1990. Prof. D. R. Osterhoff.

PMID- 9022854
TI  - Silver Medal of the SAVA: 1990. Prof. C. M. Veary.

PMID- 9022855
TI  - Nursing care of the small animal neurological patient.
AB  - Nursing care of long-term recumbent small animals, with emphasis on the
      neurological patient, is described. Principles of general nursing care,
      particularly nutritional support and the prevention and treatment of urinary
      complications, are of major concern in any weak or recumbent patient. The
      estimation of nutritional requirements and adjustments, information on South
      African commercial liquid diets and practical rehabilitation are described.

PMID- 9022856
TI  - Chemical and elemental comparison of two formulations of oleoresin capsicum.
AB  - In-custody deaths following the application of pepper spray weaponry by law
      enforcement personnel have increased in California over the last few years.
      Oleoresin capsicum (OC), an oily extract of hot peppers, is the active ingredient
      in the spray, but little detailed information on product mixtures is available.
      Since OC extracts contain a multitude of natural compounds at irregular
      concentrations, there could be considerable, variation in overall chemical
      composition among the different formulations of both 'natural' and 'synthetic' OC
      preparations. This was confirmed by organic and inorganic analyses performed on
      OC sprays produced by two manufacturers licensed for distribution within the
      state of California. The results indicated that the differences could lead to
      considerable inconsistency in weapon effectiveness, and suggested that more
      comprehensive studies are warranted.

PMID- 9022867
TI  - Intraclass correlation among measures related to tobacco use by adolescents:
      estimates, correlates, and applications in intervention studies.
AB  - Tobacco intervention studies that employ a community trial design require
      adjustment to the usual analytic methods to account for the allocation of intact
      social groups to study conditions and the positive intraclass correlation (p)
      that is inevitable in such a design. In the absence of valid estimates of the
      relevant p, investigators seeking to establish an appropriate sample size could
      only guess about the magnitude of the problem. We recently published estimates of
      p for common measures of adolescent tobacco use, but those estimates were
      unadjusted for potential covariates and so represented an upper limit on the
      magnitude of p. This report demonstrates how estimates of intraclass correlation
      may be substantially reduced through regression adjustment for easily measured
      covariates. Results show that both the p and the residual variance can be
      reduced, by an average of 20 and 11%, respectively, offering greater efficiency
      for investigators who plan future studies and who are able to measure those
      covariates in their studies. Future work should seek both to replicate this work
      and to extend it; for example, to cohort designs where the improvements might be
      even greater.

PMID- 9022868
TI  - Predicting problem drinking in college students: gender differences and the CAGE
      questionnaire.
AB  - Adolescents and young adults are among the highest users of alcohol and other
      drugs in the United States. One of the tools most commonly employed in screening
      for problem drinking and alcohol dependence is the CAGE questionnaire. Research
      has indicated, however, that not only may the CAGE be a poor detection device for
      identifying youthful substance abuse, but it may particularly lack strength in
      the detection of alcohol abuse by young women. The current study examined the
      predictive power of the CAGE relative to other common assessment indicators of
      youthful substance abuse in a sample of college students. It focused on the
      relative predictive power of the CAGE in detecting a high level of drinking
      related problems. In addition, the interaction of gender and a positive CAGE
      score was included in the logistic regression analysis to test the hypothesis
      that the CAGE is predictive for men but not for women. Results suggest that the
      CAGE is a relatively weak predictor of alcohol-related problems in this sample of
      college students, and it lacks predictive power for detecting, problems in
      college women. Issues concerning substance-abuse assessment in young people are
      discussed, with special consideration given to gender differences.

PMID- 9022869
TI  - Training chemical dependency counselors to treat nicotine dependence.
AB  - To test the effectiveness of providing chemical dependency (CD) staff with a
      knowledge-and-skills-building workshop on treatment of nicotine dependence, we
      employed a nested cross-sectional design with six outpatient CD programs in
      Nebraska (3 intervention, 3 control sites). Data on tobacco counseling provided
      by CD staff were obtained by telephone from sequential samples of smokers
      currently receiving alcohol treatment at each participating site. Intervention
      site clients with clinic visits after the staff training workshop were no more
      likely than intervention-site clients with clinic visits before the workshop to
      report having been counseled about their smoking (OR = 0.95, 95% confidence
      interval (CI): 0.74-1.21). However, control-site clients were significantly more
      likely to report having been counseled about smoking during the second half of
      the study (OR = 2.15, 95% CI: 1.49-3.08), even though staff training was not
      provided at control sites until data collection had been completed. These
      findings suggest that in some alcohol treatment programs simple monitoring of
      staff counseling practices may be sufficient to increase the frequency of
      attention to tobacco. In others, more intensive efforts might be needed to shift
      CD staff toward more consistent treatment of nicotine dependence.

PMID- 9022870
TI  - Current dieting, weight loss history, and weight suppression: behavioral
      correlates of three dimensions of dieting.
AB  - The present study investigated three dimensions of dieting (current dieting,
      history of dieting, weight suppression) and behaviors related to energy balance
      in a community sample of 999 women. The three dimensions, current dieting status,
      history of dieting, and weight suppression, were examined in relation to dietary
      intake, eating behaviors, physical activity, and weight concerns. Twenty-two
      percent of the women were current weight loss dieters, 8.3% were currently
      dieting for weight maintenance, and 69.3% were not currently dieting. Twenty
      eight percent of the women were weight suppressers. Current dieting for weight
      loss or weight maintenance was associated with lower percent of kilocalories from
      fat (33% vs. 35% among nondieters), less frequent consumption of sweet foods,
      more frequent consumption of vegetables and fruits, more frequent self-weighing,
      and lower tolerance for weight gain prior to taking action (10 lb vs. 14 lb among
      nondieters). Current dieters and those with an extensive history of dieting self
      reported a greater number of healthy and unhealthy weight loss practices during
      the past year, and they scored higher on measures of low-fat eating behaviors and
      restrained eating. Weight suppression was associated with higher physical
      activity levels and low-fat eating behaviors. Distinguishing weight suppression
      from current dieting status may provide insight into the behaviors related to
      successful weight loss maintenance, whereas measures of dieting history might be
      useful in clinical contexts.

PMID- 9022871
TI  - The effect of drink familiarity on tolerance to alcohol.
AB  - Cues associated with familiar alcoholic drinks such as beer may, through repeated
      association with the unconditioned stimulus properties of alcohol, acquire the
      status of classically conditioned stimuli. It has been proposed that such drug
      related conditioned stimuli mediate drug tolerance. Thus, the aim of the present
      experiment was to test this proposition on cognitive, subjective, and
      psychophysiological indicators of alcohol tolerance using human subjects. Two
      groups of subjects received alcohol in the form of a familiar drink (beer) or an
      unfamiliar drink (blue peppermint mixture). Both drinks contained the same dose
      of alcohol and were consumed at the same rate. Although conditioned heart rate
      and skin conductance responses occurring while subjects looked at and tasted the
      test drinks were weak, there were strong indicators of conditioned tolerance on
      the performance measures following consumption. Subjects who consumed the
      unfamiliar drink were significantly poorer on cognitive and motor tasks, and they
      rated themselves more intoxicated than did those who consumed the familiar drink.

PMID- 9022872
TI  - The impact of caffeine use on tobacco cessation and withdrawal.
AB  - Continuous caffeine consumption with smoking cessation has been associated with
      more than doubled caffeine plasma levels. Such concentrations may be sufficient
      to produce caffeine toxicity symptoms in smoking abstinence conditions. To test
      whether caffeine abstinence influences smoking cessation, 162 caffeine-using
      smokers were enlisted from American Lung Association smoking cessation programs.
      Volunteers were randomly assigned by clinic to caffeine-use and caffeine
      abstinence conditions and measured for 3 weeks post-smoking cessation, at 6
      months and one year. Results showed a significant linear increase in caffeine
      sputum levels across 3 weeks post cessation for those who quit smoking and
      continued using caffeine. Three weeks after cessation, concentrations reached
      203% of baseline for the caffeine user. Typical nicotine withdrawal symptoms
      occurred during the first 16 days of cessation. The caffeine abstainers, but not
      continued users of caffeine, reported increased fatigue during the first 3 days
      of cessation. Among complete caffeine abstainers, compared with caffeine users,
      there was a significant increase in fatigue, a decrease in stimulation, and a
      marginal increase in caffeine craving immediately following tobacco cessation.
      There were no differences between the groups on other withdrawal symptoms or in
      cessation success at 16 days, 6 months, or 12 months.

PMID- 9022873
TI  - Heavy drinking, alcohol-dependent vs. nondependent methadone-maintenance clients:
      a follow-up study.
AB  - This study of methadone-maintenance clients interviewed approximately 1 year
      after discharge from treatment revealed that outcomes differed between heavy
      drinking clients who are alcohol dependent and those who are not. Alcohol
      dependent clients seem to benefit more from treatment but continue to have severe
      cocaine-use problems, suggesting they also may be cocaine dependent. The results
      emphasized the value in differentiating between these types of drinking clients,
      and they suggest that failure to do so may account for earlier contradictory
      results about the role alcohol consumption has in treatment outcomes for
      methadone-maintenance clients.

PMID- 9022874
TI  - Identification of adolescents at risk for smoking initiation: validation of a
      measure of susceptibility.
AB  - Primary prevention of smoking in adolescents requires effective screening
      instruments for identifying those adolescents who are most likely to experiment
      with cigarettes. This study investigated the predictive value of a measure of
      susceptibility to smoking (the lack of a firm commitment not to smoke) for
      predicting smoking initiation 1 and 2 years later among 687 seventh-grade
      nonsmokers. Results showed that susceptible adolescents were approximately two to
      three times more likely to experiment with cigarettes during the ensuing 2 years
      than were nonsusceptible adolescents. At the lower levels of smoking, these
      relationships persisted even after controlling for psychosocial variables.
      Measures of susceptibility to smoking could be an effective tool for identifying
      adolescents at increased risk of experimenting with cigarettes or assessing their
      readiness for smoking-prevention programs.

PMID- 9022875
TI  - The utility of novelty seeking, harm avoidance, and expectancy in the prediction
      of drinking.
AB  - To test the hypothesis that two temperament scales (Novelty Seeking and Harm
      Avoidance) are differentially related to alcohol expectancies and drinking
      patterns, 140 adolescents from an inpatient psychiatric facility completed
      several self-report questionnaires measuring temperament, alcohol expectancies,
      and alcohol consumption. Moderated multiple regression analyses indicated that
      Novelty Seeking was significantly related to frequency of drinking and problem
      drinking, but that Harm Avoidance was not related to these variables. Results of
      the MANOVA indicated that high novelty seeking and low harm avoidant (Type 2)
      individuals had a significantly higher frequency of drinking than did individuals
      who were high on Harm Avoidance and low on Novelty Seeking (Type 1). Results also
      showed that expectancy and Novelty Seeking contributed significant independent
      and overlapping variance in the prediction of amount of drinking. Although
      Novelty Seeking was related to expectations of social functioning, other
      hypothesized relationships between temperament and expectancy were not supported.

PMID- 9022876
TI  - Do as I say: parent smoking, antismoking socialization, and smoking onset among
      children.
AB  - This study examined relationships between smoking and antismoking practices of
      parents and early onset of smoking among elementary-grade children. The parent
      practices we investigated were direct modeling of cigarette smoking and
      antismoking socialization variables, such as setting rules to eliminate cigarette
      smoking in the home, awareness of children's smoking behaviors, and making clear
      the disciplinary consequences of cigarette smoking. Surveying a sample of 1.213
      third- and fifth-grade children, we found (1) children's risk of early onset of
      smoking increases with level of exposure to parent smoking models; (2) if one or
      both parents are current smokers, children who have never tried smoking have
      significantly greater risk of intending to smoke, perceiving easy access to
      cigarettes, and being ambivalent about smoking; (3) risk rates for children of
      former smokers indicate that parents' quitting smoking does not eradicate the
      effects of parent modeling; and (4) children whose parents engage in antismoking
      socialization have significantly lower rates of smoking onset, even if parents
      are current smokers. The implications of these results for preventive
      intervention and future research are discussed.

PMID- 9022877
TI  - Alcohol expectancies: effects of gender, age, and family history of alcoholism.
AB  - To explore the effects of gender, age, and positive (FH+) and negative (FH-)
      family history of alcoholism on alcohol-related expectancies, the Alcohol
      Expectancy Questionnaire (AEQ) was administered to 627 college students (female n
      = 430). In an attempt to control for consumption effects, only individuals who
      described themselves as heavy drinkers were included in the study. A 2 (Family
      History) x 2 (Gender) x 2 (Age Range) multivariate analysis of variance (MANOVA)
      was conducted on the six scales of the AEQ. Results indicated that FH+ females
      under the age of 20 years reported stronger expectancies of social and physical
      pleasure than did FH- females. Results also suggested that females over the age
      of 20 reported significantly lower expectancies of global, positive effects
      compared to all other subjects, regardless of family history of alcoholism.
      Finally, both male and female subjects under the age of 20 reported greater
      expectancies of global, positive effects, sexual enhancement, feelings of
      increased power and aggression, and social assertion compared to individuals over
      the age of 20. These results indicate that alcohol-related expectancies vary as a
      function of age, gender, and family history of alcoholism.

PMID- 9022878
TI  - Spousal violence and cognitive functioning among men recovering from multiple
      substance abuse.
AB  - Experimental research suggests that substance use is associated with increased
      aggression, and other research suggests that substance use is also a risk factor
      in spousal violence. In addition, neuropsychological status is associated with
      both spousal violence and substance abuse. This study builds on previous work
      demonstrating an association between lower levels of performance on a brief
      neuropsychological test battery and higher levels of total couple, husband-to
      wife, and severe husband-to-wife violence for 31 married men recovering from
      multiple substance abuse.

PMID- 9022879
TI  - Incorporating social support into a community-wide smoking-cessation contest.
AB  - Social support for smoking cessation has been identified as a key factor
      differentiating which individuals are most likely to quit smoking. Attempts to
      enhance social support in clinic-based programs have generally been unsuccessful.
      This study investigated a strategy for increasing the involvement of supportive
      others among participants in a community-based smoking-cessation contest. These
      smokers were undertaking quit attempts without the supportive environment offered
      in clinic-based group programs. Subjects included 734 adult smokers who had
      participated in a smoking-cessation contest in their local community. Contest
      participants had the option of designating a "support person" who would assist
      them in quitting smoking and be eligible for prizes if the participant was a
      contest winner. Follow-up was by telephone survey 3 months after the end of the
      contest. No differences were observed in demographic or smoking history variables
      between those who did and did not elect to name a support person. A relatively
      high proportion (60%) of contest participants elected to identify a support
      person and self-reported smoking-cessation rates were significantly better among
      those who named a support person than among those who did not. Identifying a
      support person was a particularly effective strategy for those with smoking or
      nonsupportive spouses.

PMID- 9022880
TI  - A bi-directional theory of addiction: examining coping and the factors related to
      substance relapse.
AB  - The results from this study supported a bi-directional theory of addiction for a
      sample of Black, inner-city, working-class, male substance abusers. Using
      structural equations modeling, at 6 months posttreatment we found that (a) the
      reciprocal effect emotional and psychological distress and substance relapse had
      on one another existed within the context of their bi-directional relationship
      with social instability, and (b) effective coping skills and resources moderated
      the negative effects that emotional and psychological distress, social structure,
      and substance relapse had on one another. These findings led us to three
      suggestions treatment professionals can use to counteract recidivism.

PMID- 9022881
TI  - Effects of gestation dating in Down's screening.

PMID- 9022882
TI  - Evidence-based clinical biochemistry.

PMID- 9022883
TI  - Proposals for setting generally applicable quality goals solely based on biology.

PMID- 9022884
TI  - Enzyme standardization--the way forward?

PMID- 9022886
TI  - Steroid profiling.

PMID- 9022885
TI  - Glycated haemoglobin analysis.

PMID- 9022887
TI  - Clinical indications for the use of urinary steroid profiles in neonates and
      children.
AB  - For a number of rare adrenal disorders, some of which are life threatening in
      childhood, laboratories need access to specialist endocrine investigations.
      Measurements of hormones in blood samples may be diagnostic in some cases but not
      all of the requisite steroid hormone assays are available. Multiple plasma
      steroid measurements may be required to prove the nature of a steroid
      biosynthetic disorder but in newborn children immunoassays, performed without
      prior solvent extraction, can be misleading. A urine steroid profile by gas
      chromatography coupled with mass spectrometry examines many steroid metabolites
      simultaneously and provides specific diagnostic information. A urine steroid
      profile can provide precise information of the secretory nature of tumours and
      causes of virilization, salt loss and hypertension often from a spot urine sample
      rather than a 24 h collection. However, a steroid profile is not helpful in
      making a diagnosis in neonatal genetic males with poorly developed genitalia.

PMID- 9022888
TI  - The effects of gestation dating on the calculation of patient-specific risks in
      Down's syndrome screening: multivariate case.
AB  - When screening for Down's syndrome using biochemical markers, the measurements
      are adjusted for the gestational age of the fetus because the concentrations of
      the markers are known to change with gestational age. This adjustment is
      performed by referring each marker measurement to the population median for that
      marker for the appropriate estimated gestational age group. The measurement of
      gestational age is subject to error, whichever method is used, and so the
      population median used is usually the median of a mixture of distributions for
      different true gestational ages. Most screening programmes aim for a specific
      number of weeks and this produces a concentrated distribution of true gestational
      ages. This fact, combined with dating errors, leads to an asymmetric mixture for
      each gestational age group and hence to bias in the estimates of the medians. In
      a previous communication we have shown how the proportions in this mixture
      distribution can be estimated and how the true medians corresponding to a true
      gestational age can be estimated. The calculations presented were performed using
      a single marker, and the details of our method were restricted to this situation.
      This paper extends the method to the multimarker situation and, as expected,
      leads to a gain in the detection rate for a specified false positive rate. The
      true patient-specific risk estimates are again markedly different from the quoted
      nominal value obtained by ignoring the dating errors. The data set on which the
      method is illustrated uses two markers, although the technique generalises in an
      obvious way to more than two.

PMID- 9022889
TI  - Micro-extraction of commonly abused benzodiazepines for urinary screening by
      liquid chromatography.
AB  - We have developed a micro-extraction procedure for the analysis of seven commonly
      prescribed benzodiazepines (chlordiazepoxide, diazepam, lorazepam, nitrazepam,
      nordiazepam, oxazepam, and temazepam) in urine using liquid chromatography. The
      method is reliable and sensitive, uses small volumes (100 microL) of urine and is
      suitable for the detection and quantification of low concentrations of
      benzodiazepines. The micro-extraction procedure allowed rapid sample processing,
      which is important for routine sample handling. The limit of detection for the
      seven benzodiazepines ranged from 0.10-0.71 mg/L and recovery of the different
      benzodiazepines was good, ranging from 70-105%. Between- and within-assay
      coefficients of variation ranged from 6.3% to 13.8%, and 2% to 3.5%,
      respectively. Chlordiazepoxide chromatographed poorly (between assay coefficient
      of variation 35.4%, within-assay 7%), and we set the cut-off value for this
      compound at 5.0 mg/L.

PMID- 9022890
TI  - Benzodiazepine misuse by drug addicts.
AB  - Using a high-performance liquid chromatography method, we measured seven commonly
      prescribed benzodiazepines (chlordiazepoxide, nitrazepam, nordiazepam, oxazepam,
      lorazepam, temazepam and diazepam) in 100 urine samples obtained from patients
      attending the Leeds Addiction Unit. All of the urines selected for investigation
      were positive for benzodiazepines using an EMIT (Enzyme Immunoassay) screen.
      Forty-four of the urines contained a range of benzodiazepines, none of which had
      been prescribed. Nitrazepam was detected most frequently (61 urine samples), but
      had not been prescribed to any of the patients in this study. Chlordiazepoxide
      was detected in 49 urine samples, although it had been prescribed to only five
      patients. Temazepam was detected in 28 urine samples. Fourteen patients providing
      21 urine samples had been prescribed temazepam for treatment. However, temazepam
      was detected in only 14 of these samples. Multiple benzodiazepine abuse was
      evident from the high rate of detection of unrelated benzodiazepines.

PMID- 9022891
TI  - Evaluation of Bionike one-step tests for the detection of drugs of abuse in
      urine.
AB  - Bionike one-step tests were used to screen urine samples for amphetamines,
      methamphetamines, benzodiazepines, cannabinoids, methadone and opiates, and
      results were compared with those obtained using enzyme multiplied immunoassay
      technique d.a.u. assays. Taking into consideration different threshold levels and
      possible differences in cross-reactivities, there was good agreement between the
      methods. Results of Bionike tests correlated well with amphetamines, methadone
      and opiates detected in urine using gas chromatography-mass spectrometry. Bionike
      methods are rapid, simple to use, and relatively inexpensive for on-site testing
      of individual drugs or groups of drugs in urine.

PMID- 9022892
TI  - Assessment of an automated immunoassay based on kinetic interaction of
      microparticles in solution for determination of opiates and cocaine metabolite in
      urine.
AB  - A recently introduced automated immunoassay which is based on kinetic interaction
      of microparticles in solution (Roche ONLINE), was evaluated for the detection of
      cocaine metabolite benzoylecgonine (BE) and opiates in human urine. Cross
      reactivity for the opiates morphine (100%), codeine (88%), 6-monoacetylmorphine
      (88%), and morphine 3-glucuronide (72%) was assessed. Analytical recovery
      evaluated on blank urines spiked with 0, 250, 300, 350, and 500 micrograms/L of
      morphine and BE (n = 10), varied from 85.2 to 100.2% for opiates and from 81.4 to
      93.1% for the cocaine metabolite. The within-day precision ranged from 1.4 to
      4.7% for morphine and from 4.2 to 4.8% for BE. The repeatability of the standards
      over 1 month was 1.0-3.3% for opiates and 1.7-5.1% for BE, and thus allowing
      measurements to continue over 30 days without re-calibration. This method
      compared favourably with the SYVA EMIT d.a.u system and gas chromatography/mass
      spectroscopy (GC/MS) methods.

PMID- 9022893
TI  - Serum total antioxidant activity after myocardial infarction.
AB  - Serum total antioxidant activity (TAA), albumin and uric acid were measured on
      admission, and for the next 2 days in 56 patients suffering myocardial
      infarction, 20 of whom received streptokinase. The 'antioxidant gap', the
      difference between the serum TAA and the sum of the serum albumin and uric acid
      activity, was calculated. No significant changes in serum total antioxidant
      activity were observed in either group of patients between admission, day 1 and
      day 2. However, a decline in the 'antioxidant gap' after myocardial infarction
      was associated with a significantly higher mortality.

PMID- 9022894
TI  - Ovarian steroids regulate the expression of basic fibroblast growth factor and
      its mRNA in fibroblasts derived from uterine endometrium.
AB  - The role of stromal cells in basic fibroblast growth factor (FGF) supply for
      endometrial neovascularization during the menstrual cycle was investigated. The
      concentrations of intracellular and secreted FGF, and FGF mRNA expression were
      determined in fibroblasts derived from uterine endometrium as a substitute for
      stromal cells. The influence of sex steroids on protein and mRNA expression was
      investigated. The concentration of FGF and its mRNA expression in the fibroblasts
      was significantly increased by oestradiol, and these increased concentrations
      were diminished by progesterone. It is suggested that oestrogen stimulates FGF
      secretion from the stromal cells, an effect which is inhibited by progesterone.
      Therefore, endometrial neovascularization might be partially regulated by stromal
      derived FGF under the influence of sex steroids, through a paracrine cell-to-cell
      interaction.

PMID- 9022895
TI  - Evaluation of a new, rapid and automated immunochemiluminometric assay for the
      measurement of serum intact parathyroid hormone.
AB  - The Immulite parathyroid hormone (PTH) immunochemiluminometric assay (ICMA) was
      evaluated by measuring serum PTH concentrations in 134 volunteers and 25 patients
      with various diseases affecting bone and mineral metabolism and comparing with
      those measured by the Nichols Allegro immunoradiometric (IRMA) assay. Although
      the assays were highly correlated (r = 0.99. P < 0.0001), there were
      discrepancies at lower PTH concentrations which may be explained by the lower
      limit of detection of the ICMA assay. The anti-coagulants EDTA and heparin
      appeared to have significant effects on PTH measurement particularly at lower
      concentrations. Sera assayed by ICMA diluted out more uniformly than in the IRMA
      and there was no cross reactivity with parathyroid hormone-related peptide in
      either the IRMA or ICMA. Delays of up to 8 h in specimen handling did not appear
      to affect PTH measurements. The enhanced sensitivity of the Immulite ICMA intact
      PTH assay confers an advantage in the diagnosis of both hyper- and hypocalcaemia,
      while the shorter incubation times, automation and lack of radioactivity are
      important practical advantages.

PMID- 9022896
TI  - Near-patient testing by proxy.

PMID- 9022897
TI  - Six alternative methods to the lecithin/sphingomyelin ratio in amniotic fluid for
      assessing fetal lung maturity.

PMID- 9022898
TI  - Bilirubinuria, conjugated hyperbilirubinaemia and delta bilirubinaemia following
      acute haemolysis.

PMID- 9022899
TI  - Critical care hypercalcaemia.

PMID- 9022900
TI  - Fibrates and HDL cholesterol.

PMID- 9022901
TI  - The short Synacthen test: with 1 microgram or 250 micrograms ACTH?

PMID- 9022902
TI  - Seasonal growth patterns in rural Nepali children.
AB  - This paper reports on the prevalence of growth retardation, the impact of
      seasonality on height and weight gains, and significant relationships between
      growth velocity, nutritional status and morbidity, for a population living at
      subsistence level in rural Nepal. Monthly variation in growth pattern was
      examined for 71 boys and girls 0-49 months of age. At the height of the monsoon
      season, 71% of children were moderately stunted, but none was wasted (mean -2.61
      SD height-for-age and -0.91 SD weight-for-height by reference to NCHS z-score
      values). Measures of stunting deteriorated from moderate to severe after 1 year
      of age. No differences by sex or ethnicity were detected. Environmental changes
      from the winter to the monsoon seasons were reflected in significant losses of
      weight and lower weight-for-height z-scores, especially for 0-35 month-olds,
      although height for 12-35-month-olds continued to be gained over this period.
      Growth velocity was significantly related to previous growth status (thinner and
      shorter children did not show catch-up in height or weight) and to morbidity
      reported over the period of observation. The prevalence of illnesses rose six
      fold from the winter to the monsoon, and children with a high frequency of
      illnesses experienced a significant shortfall in weight and height increments. A
      poor diet and recurrent illnesses explain the slow and uneven growth of these
      children. Despite an increase in women's agricultural workloads in the monsoon
      season, childcare patterns per se do not seem to adversely affect small children.
      Small stature through later childhood and in adults is one consequence of the
      growth pattern seen at these young ages.

PMID- 9022903
TI  - Maturity-associated variation in peak oxygen uptake in active adolescent boys and
      girls.
AB  - Maturity-associated variation in peak O2 uptake was considered in a longitudinal
      sample of 47 boys and 40 girls who were enrolled in sports schools. The children
      were followed annually from 11 to 14 years of age. O2 uptake and heart rate were
      measured during a maximal exercise test on a cycle ergometer. For boys,
      individual velocity curves were used to operationally define maturity groups:
      early-decreasing velocities from 11 to 14 years, n = 9; average-velocities
      reaching a peak and then decreasing, n = 7; and late-increasing velocities from
      11 to 14 years, n = 31. The distributions of stages of genital and public hair
      development were consistent with early, average and late maturity status
      designation based on velocities of stature growth. Prospectively collected ages
      at menarche were used to define maturity groups in girls: early--< 12.0 years, n
      = 7, 10.8 +/- 0.6 years; average--12.0.12.9 years, n = 20, 12.4 +/- 0.3 years;
      and late-- > or = 13.0 years, n = 13, 13.5 +/- 0.4 years. Early maturing boys had
      a greater O2 uptake at each observation period. Early and average maturing girls
      did not differ in maximal O2 uptake, but both had greater O2 uptake than late
      maturers. When expressed per unit body mass, differences among the three maturity
      groups of boys were reduced and not significant. Late maturing girls tended to
      have greater maximal O2 uptake per unit body mass than early and average maturing
      girls, but the differences were not significant at all ages. However, with body
      mass at the first observation as the covariate in analyses of covariance, the
      three maturity groups of boys differed significantly in peak VO2 at each
      observation, while the three maturity groups of girls did not. Thus, removing the
      confounding effect of body mass on O2 uptake by simply dividing the measured
      values by mass is of limited utility.

PMID- 9022904
TI  - Longitudinal study of ontogenetic allometry of oxygen uptake in boys and girls
      grouped by maturity status.
AB  - The utility of removing the confounding effect of body mass on oxygen uptake by
      simply dividing the measured values by mass has been questioned: Allometric
      transformation or calculation of covariance analysis have been proposed as more
      appropriate alternatives. This study hypothesized that scaling factors for
      individual youths differ with maturity status. Peak oxygen uptake (peak VO2)
      during exercise on a bicycle ergometer, stature and body mass were measured at
      annual intervals in 47 active boys and 31 active girls from 11 to 14 years of
      age. All subjects attended sport schools during the study. The children were
      classified into two maturity categories, early and average (for the sake of
      sample size and consistency between sexes), and late on the basis of individual
      stature velocities in boys and age at menarche in girls. Individual data for peak
      VO2 were normalized for differences in body mass by double logarithmic
      transformation and regression analysis (ontogenetic allometry). Individual
      allometric coefficients (mean +/- SD) for boys showing a good fit were,
      respectively, 0.799 +/- 0.239 and 0.536 +/- 0.141 in early and average maturing
      boys combined and in late maturing boys. Logarithmic transforms of VO2 and mass
      were highly related (r > 0.90) in 10 of 16 early and average maturers, and in 18
      of 31 late maturers. Corresponding individual allometric coefficients in girls
      were more variable, and the logarithmic transforms of VO2 and mass were not
      highly related (r < 0.70). Similar results were obtained for the relationships
      between the logarithmic transforms of VO2 and stature. The evidence thus suggests
      that in boys scaling VO2 for body mass varies with maturity status of the
      individual, and that there is considerable inter-individual variation in scaling
      coefficients during early and mid-adolescence. The increase in peak VO2 in active
      girls 11-14 years is not related to the increase in body mass or stature in the
      majority.

PMID- 9022905
TI  - Menopause-associated differences in female fat patterning estimated by dual
      energy X-ray absorptiometry.
AB  - The aim of the present study was to describe and quantify the typical changes in
      fat patterning from premenopause to postmenopause. The absolute and relative fat
      and lean body mass were estimated using dual-energy X-ray absorptiometry in 461
      healthy non-obese females between the ages of 18 and 64 years (x = 43.2).
      Significant differences (p < 0.001) in absolute and relative fat mass, body
      weight and body mass index between pre-, peri- and postmenopausal females were
      observed. Postmenopausal women were significantly heavier (BMI, x = 26.8) than
      perimenopausal (BMI, x = 24.4) and younger and older premenopausal women (BMI, x
      = 22.8) and showed significantly higher fat percentages (fat% x = 38.1) in
      comparison to perimenopausal (x = 36.8) and premenopausal females (x = 31.4).
      Three indices, upper body composition index, lower body composition index and fat
      distribution index were calculated. Typical differences in fat distribution
      patterns between females of differential menopausal status were found. During the
      premenopausal phase a more gynoid type of fat distribution prevailed, during the
      postmenopausal phase a more android kind of fat distribution occurred
      predominantly. The fat distribution during the perimenopause can be interpreted
      as less gynoid than during the premenopause.

PMID- 9022906
TI  - Adult height and menarcheal age of young women in Greece.
AB  - Several factors contribute to the attainment of adult height, including genetic
      and environmental variables. To assess the relationship between menarcheal age
      and adult height, measured height was regressed on recalled menarcheal age in 286
      young women, 18-24 years old, candidates for recruitment in the Greek army.
      Height was significantly associated with menarcheal age (b = 0.52, 95% CI = 0.04
      1.00, p = 0.03). Joint evaluation of age, body mass index (BMI) and menarcheal
      age as predictors of final height revealed that only age at menarche represents
      an independent predictor of final height. Finally, education in completed years
      of schooling and place of birth or residence did not influence adult height, and
      no interaction between age at menarche and these factors was observed in the
      present study. These data suggest that adult height of Greek women is
      independently associated with menarcheal age, whereas BMI, place of birth or
      residence and educational level do not seem to play a role of comparable
      significance.

PMID- 9022907
TI  - Accuracy of short-term recall of age at menarche.
AB  - This study was conducted as part of the third annual follow-up of a cohort of 657
      girls to test the accuracy of short-term recall of age at menarche. During the
      first and second annual follow-ups of the cohort, 101 girls had reported
      menarche. We sent questionnaires to these subjects at the third annual follow-up
      and asked them to recall the month and year of their menarche. Eighty-eight
      respondents returned their questionnaires with the relevant information. Overall,
      59.1% of the respondents were able to recall their menarche with the exact month
      and year. The mean recall interval was 430 days. When the data were grouped by
      the interval of recall, higher accuracy was observed with a shorter interval of
      recall. With a mean interval of recall of 323 days, 66.1% of the subjects were
      able to recall their menarche correctly, whereas with a mean interval of 649
      days, only 44.8% of the subjects were able to recall correctly.

PMID- 9022908
TI  - No evidence for saltation in human growth.

PMID- 9022909
TI  - The induction of polyclonal B-cell activation and interleukin-1 production by the
      75-kDa cell surface protein from Porphyromonas gingivalis in mice.
AB  - The immunobiological activities of 75-kDa protein, fimbrial protein and
      lipopolysaccharide lipopolysaccharide prepared from whole cells of Porphyromonas
      gingivalis 381 were compared. The 75-kDa protein was mitogenic for BALB/c nu/nu,
      BALB/c and lipopolysaccharide-responsive C3H/HeN mouse spleen cells and for
      lipopolysaccharide-non-responsive C3H/HeJ mouse spleen cells. The response was
      significant in BALB/c mouse spleen cells incubated with 1-100 micrograms/ml of
      the 75-kDa protein. Furthermore, the 75-kDa protein exhibited polyclonal B-cell
      activation in murine spleen cells, which was similar to the lipopolysaccharide of
      P. gingivalis. In contrast, fimbriae from P. gingivalis did not, or only weakly,
      activated murine spleen cells. C3H/HeN mouse macrophages exposed to 10
      micrograms/ml of the 75-kDa protein released large amounts of interleukin-1 (IL
      1), which were maximal for 48 h, whereas IL-6 activity in macrophage supernatants
      was not detected throughout the culture period. These results suggest that the 75
      kDa protein is a potent polyclonal B-cell activator and that it stimulates IL-1
      production from murine peritoneal macrophages as well as lipopolysaccharide,
      which may play an important part in the inflammatory response during the
      development of periodontal diseases.

PMID- 9022910
TI  - Low molecular-weight proteins in human gingival crevicular fluid.
AB  - Samples of gingival crevicular fluid (GCF) were collected in 30 volunteers with
      inflamed gingiva, using either capillary tubes (cGCF) or Durapore strips (sGCF).
      They were examined, together with samples of serum from the same patients, by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis and/or by two
      dimensional electrophoresis, followed by silver staining. The results confirmed
      that the distribution of the major proteins in GCF is similar to that found in
      serum. However, an 8.5 kDa protein was found in gingival fluid but not in serum.
      The low molecular-weight protein appears to decrease with time of fluid sampling
      with both techniques, and does not originate either from blood or from the
      cellular fraction of GCF. Two-dimensional electrophoretic analysis suggested that
      it may consist of several polypeptides.

PMID- 9022911
TI  - Morphometry and autoradiography of altered rat enamel protein processing due to
      chronic exposure to fluoride.
AB  - Female Sprague-Dawley rats had 6 weeks of 0 (control), 75 or 100 parts/10(6)
      sodium fluoride in their drinking water. Whole mandibular incisors were removed,
      fixed, demineralized and sections prepared for light-microscopic morphometric
      analysis of dose-related alterations in enamel protein retention. Other rats
      given 0 and 75 parts/10(6) only (control and experimental groups) were used for
      autoradiographic evaluation of alterations in enamel protein removal 35S
      methionine was applied directly over secretory ameloblasts at the end of the
      fifth week of fluoride exposure. Incisors were removed either 5 or 7 days later
      and processed for autoradiographic analysis. The results indicated: (1) extended
      retention of enamel proteins in fluoride-exposed maturation enamel as well as
      reduced enamel protein synthesis and/or secretion in the secretory stage; (2)
      negative linear correlation between extended enamel protein retention and reduced
      enamel protein secretion among groups; and (3) repression of enamel protein
      removal. The data are also consistent with the concept that the fluoride effect
      is multifactorial.

PMID- 9022912
TI  - Postnatal development of substance P-, calcitonin gene-related peptide- and
      neuropeptide Y-like immunoreactive nerve fibres in the synovial membrane of the
      rat temporomandibular joint.
AB  - The postnatal (0-24 days) development of substance P (SP)-, calcitonin gene
      related peptide (CGRP)- and neuropeptide Y(NPY)-like immunoreactive (LI) nerves
      in the rat temporomandibular joint (TMJ) was investigated immunohistochemically.
      Immediately after birth, SP- or CGRP-LI nerves were observed in most disc
      attachments. A few NPY-LI nerves were observed around the large blood vessels in
      the joint capsule. From days 3 to 6, the SP- or CGRP-LI nerves were first found
      close to the anterior, lateral, medial (third day) or posterior (sixth day)
      peripheral portion of the disc. The synovial cells (type A and B) first appeared
      at the anterior peripheral portion of the disc (sixth day), and then at the
      posterior, lateral and medial portions (seventh day). NPY-LI nerves were found
      around the blood vessels at the disc attachment on the sixth day, and then
      entered into the peripheral portion of the disc from days 10 to 14. At 14 days a
      few NPY-LI nerves were first found close to the blood vessels in the sublining
      layer of the synovial membrane. From days 18 to 24, a few NPY-LI nerves were
      located in the superficial layer of the synovial membrane. The central portion of
      the disc did not contain any nerves from days 0 to 24. Thus SP- or CGRP-LI
      sensory nerves are shown to innervate the rat TMJ at an earlier age than NPY-LI
      sympathetic nerves, which may modulate the regulation of blood flow in the joint
      capsule, disc and synovial membrane. However, it is considered that the disc
      itself does not contribute to the transportation of the afferent sensory
      information. Furthermore, from the fact that SP- or CGRP-LI nerves were found
      earlier than the appearance of the synovial cells, it is suggested that these
      nerves may be associated with the growth and proliferation of synovial cells.

PMID- 9022913
TI  - Cellular, biochemical and molecular characterization of the bovine
      temporomandibular joint disc.
AB  - The cellular and collagenous components of the bovine temporomandibular joint
      (TMJ) disc have been isolated and analysed. In the central regions of the disc,
      significant amounts of type I, II, IX and XII collagen were found. The identity
      of these molecules was verified with collagenase digestions, Western blot
      analysis and Northern blot analysis (for type II collagen). Cells isolated from
      the TMJ disc synthesized alkaline phosphatase, proteoglycans and collagen in
      culture; however, the basal rate of synthesis for these molecules was lower than
      that for isolated osteoblasts, articular and growthplate chondrocytes. The TMJ
      disc cells proliferated more rapidly in culture than osteoblasts or chondrocytes.
      Transforming growth factor-beta stimulated proliferation by 250%, whereas
      prostaglandin E2 had no effect.

PMID- 9022915
TI  - Continuous overnight observation of human premolar eruption.
AB  - Such observation was made possible by transmitting the image of a mobile ceramic
      ruling on the erupting maxillary second premolar to a video-microscope via a
      coaxial fibreoptic cable. The cable was inserted into a reference bar secured to
      the adjacent first molar and first premolar. The image of the ruling was
      superimposed with the image from a surveillance camera focused on the patient and
      continuously recorded on video-tape along with the participant's blood pressure,
      pulse rate, electromyographic activity and occlusal contact sounds. Overnight
      data from 12 individuals clearly revealed a circadian rhythm in eruption during
      the prefunctional spurt. On average, the maxillary second premolar erupted 41
      microns during an 11-h overnight observation, with almost all the eruption
      occurring in the late evening from 8 p.m. to 1 a.m. After 1 a.m., eruption
      typically ceased, with a tendency for intrusion to occur until 7 a.m. Sleep
      increased the rate of eruption during the late evening, but did not influence the
      eruption rate during the early morning. Haemodynamic changes, including blood
      pressure and pulse rate, did not have a significant impact on the rhythm of
      eruption. The observed eruption rhythm is most probably caused by changing
      hormone levels and their effect on the periodontal ligament. The late-evening
      eruption of human premolars coincides with the late-evening secretion of growth
      hormone and thyroid hormone typically found in humans.

PMID- 9022914
TI  - Response of rat salivary glands to mastication of pelleted vitamin A-deficient
      diet.
AB  - Interpretation of previous studies of the effects of hypovitaminosis. A on
      salivary glands is confounded by the atrophic effects of liquid or powdered
      diets. The purpose of this study was to reevaluate the effects of vitamin. A
      deficiency on the morphology and function of rat salivary glands using a pelleted
      diet that promotes physiological levels of masticatory stimulation. Profound
      vitamin A deficiency resulted in a marked decrease in stimulated parotid
      secretion. Histological evaluation demonstrated the development of squamous
      metaplasia in the ducts of parotid, submandibular and sublingual salivary glands;
      however, atrophy was observed only in serious salivary glands. In the parotid
      gland the degree of atrophy corresponded to the decrease in stimulated secretion.
      Mild hypovitaminosis A (before the development of squamous metaplasia in ducts)
      was associated with distinctly different effects. The parotid gland was
      moderately enlarged. There was also a significant increase in stimulated
      secretion, which was not explained by changes in gland size, muscarinic receptor
      number or affinity, or receptor-mediated calcium signalling.

PMID- 9022916
TI  - Antagonistic effect of D-myo-inositol-1,2,6-trisphosphate (PP56) on neuropeptide
      Y-induced vasoconstriction in the feline dental pulp.
AB  - Intra-arterial injection of neuropeptide Y (NPY) (1.3-2.0 micrograms/kg) resulted
      in decreases of pulpal blood flow by 37.7 +/- 5.7% (mean +/- SEM). The intra
      arterial injection of D-myo-inositol-1,2,6-trisphosphate (PP56) (0.3 mg/kg) alone
      changed pulpal blood flow by 1.0%. The effect of NPY in the presence of PP56
      resulted in significantly smaller decreases in pulpal blood flow ranging from
      27.2 +/- 5.4 to 16.6 +/- 3.5% from control as compared with NPY alone. In effect,
      PP56 partially blocked the decreases in pulpal blood flow caused by NPY. The
      electrical stimulation of the sympathetic nerve alone resulted in decreases in
      pulpal blood flow of 41.7 +/- 6.2%. The electrical stimulation of the sympathetic
      nerve following the intra-arterial administration of PP56 decreased pulpal blood
      flow by 23.1 +/- 6.0% from control, significantly less than the sympathetic nerve
      stimulation alone. PP56 attenuated the decrease in pulpal blood flow caused by
      the sympathetic nerve stimulation by 44.4 +/- 11.0%. Similarly, the combination
      of PP56 and phentolamine followed by electrical stimulation of the sympathetic
      nerve reduced the decrease in pulpal blood flow caused by the sympathetic nerve
      stimulation alone by 43.0 +/- 8.6%. These results provide evidence that the non
      peptide PP56 is capable of antagonizing vasoconstriction caused by NPY in the
      feline dental pulp. In addition, they show functional evidence that NPY as well
      as noradrenaline are released from the sympathetic nerve endings during its
      stimulation and cause vasoconstriction.

PMID- 9022917
TI  - A histological study on the effect of different periods of orthodontic force on
      the innervation and dimensions of the cat periodontal ligament.
AB  - Using light microscopy, the numbers of myelinated axons in the periodontal
      ligament of the cat mandibular canine were counted after orthodontic forces had
      been applied for either 3 days or 12 weeks, and also 8 weeks after removal of a
      force that had been applied for the previous 12 weeks. After 3 days no
      significant changes in axon number were recorded, but after 12 weeks there were
      significantly fewer myelinated axons in the periodontal ligament of the
      experimental teeth than in the control teeth. This reduction was not reversed
      after an 8 week recovery period. The width of the ligament was measured in an
      attempt to correlate regions of nerve fibre degeneration with areas of
      compression or tension, and the tooth root circumference was measured to assess
      the extent of any root resorption. It appeared that axon degeneration occurred
      both in areas of compression and tension. Root resorption had occurred after 12
      weeks of applied force and there was no significant change after the 8 week
      recovery period. These findings support the view that nerve injury occurs as a
      result of orthodontic force and may possibly be permanent.

PMID- 9022918
TI  - Use of a paper-strip absorption method to measure the depth and volume of saliva
      retained in embrasures and occlusal fussae of the human dentition.
AB  - Embrasures and occlusal fossae are regions of the human dentition that readily
      retain saliva, as well as dental plaque and dietary substrates. In this study, a
      wax filling and weighing technique was used to determine the volumes of these
      irregularly shaped spaces, and a paper-strip absorption method was developed for
      measuring the thickness and amounts of saliva therein. The volumes were measured
      on dental stone models prepared from alginate impressions of the maxillary arches
      of each of eight individuals and on an acrylic maxillary denture representative
      of the shape and alignment of normal-sized adult teeth. Embrasure volumes in the
      two cases were similar and ranged between 4.0 and 16.4 microliters for the
      individual participants, and between 4.8 and 14.9 microliters for the denture.
      Occlusal fossae volumes of posterior teeth determined on the denture ranged
      between 6.0 and 9.8 microliters. The paper-strip absorption method for the
      thickness or amount of saliva in embrasures or fossae consisted of the absorption
      of the saliva in these sites on to filter-paper strips and the measurement of the
      collected volumes electronically with a Periotron 6000 micro-moisture meter.
      Residual saliva for the embrasures between the two central incisors and the
      second premolar and first molar ranged between 0.12 and 0.56 with means of 0.28
      and 0.37 microliter, respectively, for the same eight participants. Corresponding
      saliva Vmax volumes were 0.48 and 0.63 microliter, respectively. Further paper
      strip absorption measurements of saliva in embrasures and fossae showed a linear
      relation between Periopaper dipstick values and embrasure saliva volumes when
      these were less than 1 microliter. This range includes most residual saliva
      volumes normally found in these sites in vivo. For volumes of saliva greater than
      1 microliter, small increments in dipstick values in embrasures corresponded to
      very large changes in total embrasure volumes, which reflects their exponential
      widening beyond about that point. For saliva thickness measurements, a blue food
      dye was used to construct a standard curve relating depth of saliva in embrasures
      and fossae (measured with an electronic micrometer) to Periopaper dipstick scores
      (measured with the Periotron). The relation was linear for both sites, with r
      values of 0.98 and 0.99, respectively (p < 0.001 for each), and was used to
      convert extensive in vivo depth measurements of embrasures and fossae determined
      in microlitres by the dipstick method in an earlier study to thicknesses in
      millimetres here. In the earlier study, residual saliva on oral mucosal and
      smooth dentition surfaces was quantified by the blotting method. Together with
      the method developed here, it should now be possible to measure the saliva,
      residual or otherwise, on all oral surfaces whether uniform or irregular in
      shape.

PMID- 9022919
TI  - Typing of mutans streptococci by arbitrarily primed polymerase chain reaction.
AB  - The discriminative power of the arbitrarily primed polymerase chain reaction (AP
      PCR) in differentiating between Streptococcus mutans and Strep. sobrinus species,
      serotypes and clones was investigated. Mutans streptococcal isolates (12(7))
      obtained from 65 individuals (1-10 isolates per individual) were AP-PCR typed
      separately with two random primers, OPA-05 and OPA-13. Bacterial cell lysates
      were used as a template in PCR reactions, which made AP-PCR easy and fast to
      perform. Eighty-one isolates from 19 individuals were also ribotyped to compare
      the discriminative ability of ribotyping and AP-PCR techniques. AP-PCR performed
      with the two primers differentiated between Strep. mutans and Strep. sobrinus
      isolates, but neither primer detected serotype-specific amplification products.
      OPA-05 distinguished two main AP-PCR patterns among Strep. mutans isolates and
      one main pattern among Strep. sobrinus isolates, whereas OPA-13 found one main AP
      PCR pattern among Strep. mutans isolates and two main patterns among Strep.
      sobrinus isolates. Ribotyping and AP-PCR revealed 40 and 33 different types among
      81 selected isolates, respectively. Both techniques detected intra-individual
      heterogeneity in 16 out of 19 participants. The results indicate that AP-PCR has
      good discriminative ability in differentiating between mutans streptococcal
      clones and that the technique is suitable for epidemiological studies on mutans
      streptococci.

PMID- 9022920
TI  - Expression of bone sialoprotein mRNA by cells lining the mouse tooth root during
      cementogenesis.
AB  - Adhesion molecules are considered to have an active role in controlling cell
      differentiation, although the mechanisms involved have yet to be determined. The
      developing tooth provides an excellent model to use for determining the
      factors/processes regulating cell differentiation. The studies presented here
      focused specifically on the timed and spatial expression of a bone-associated
      adhesion molecule, bone sialoprotein, during tooth root development. Mandibular
      tissues in the first molar region of CD-1 mice, at sequential stages of
      development, were analysed by in situ hybridization. The results demonstrate
      distinct expression of bone sialoprotein in surrounding bone at early stages of
      tooth development. At stages of active cementogenesis, bone sialoprotein
      transcripts were specific to cells lining the root surface, with limited
      expression in the surrounding connective tissue (periodontal ligament) region.
      The strong expression of bone sialoprotein, a mineral-specific protein having the
      capacity to act as a nucleator of hydroxyapatite in vitro, by cells lining the
      root surface at early stages of cementogenesis suggests that this molecule is
      operative in the cell/matrix events that accompany cementum formation.

PMID- 9022921
TI  - Effects of pulsatile versus non-pulsatile pulpal pressure simulations on
      diffusional transport across human dentine in vitro.
AB  - The influence of a simulated pulsatile pulpal pressure on the diffusion of NaCl
      through slices of human dentine (n = 12) was evaluated in vitro. The average
      hydraulic conductance of the slices of dentine was 0.0131 +/- 0.0031
      microliter/cm2 per min per cmH2O(x +/- SD). A 1 mol/l NaCl solution was placed on
      one side of the slices of dentine and deionized water on the other side. The time
      needed to reach a steady state and the quantity of NaCl that diffused through the
      slice were successively measured on the same slice of dentine, under three
      conditions: without pressure simulation, with a static pressure of 1.5 kPa, and
      with a pulsatile pressure varying from 1.2 to 1.8 kPa. The pressure was applied
      to the deionized water. When a static pressure was applied, the time required to
      reach a steady state increased from 24 to 30 h. When a pulsatile pressure was
      applied the time required to reach a steady state decreased from 24 to 12 h. No
      statistically significant difference was found between the quantity of NaCl that
      had diffused when the steady state was reached.

PMID- 9022922
TI  - Changes in the chemical composition of the bovine temporomandibular joint disc
      with age.
AB  - The bovine temporomandibular joint disc is a fibrocartilaginous structure
      composed largely of collagen and proteoglycans. Little is known about changes in
      its composition accompanying growth and maturation. Discs were collected from
      immature foetuses (3-5 months), mature foetuses (6-8 months, adolescents (18
      months), young adults (2-3 yr) and mature adults (over 4 yr), dissected free of
      fibrous attachments, and separated into outer and inner tissues. For the outer
      tissues the major findings were that: (1) water content in postnatal specimens
      was less than in prenatal specimens: (2) collagen content (relative to tissue dry
      weight) increased up to adolescence with little change thereafter; (3) total
      glycosaminoglycan, chondroitin sulphate and hyaluronic acid contents decreased
      during foetal development and then remained relatively constant, and (4) dermatan
      sulphate (the major glycosaminoglycan at all ages) decreased at maturity while
      keratan sulphate increased slightly. Results for the inner tissues were similar
      except that: (1) total glycosaminoglycan content was much higher in postnatal
      animals; (2) chondroitin sulphate was the major glycosaminoglycan after birth;
      and (3) keratan sulphate, which was barely detectable in the foetal specimens,
      increased rapidly after birth. Evidence was also obtained for changes in the
      copolymeric nature of galactosaminoglycans in the inner tissue. These findings,
      especially the different pattern of age-related changes in outer (presumably non
      compressed) and inner (presumably compressed) tissue, suggest that the disc has
      the capacity to continually modify its composition in response to the mechanical
      stresses placed on it.

PMID- 9022923
TI  - Metabolism of extracellular ATP by rat parotid cells.
AB  - ATP hydrolysis and the products of ATP metabolism were measured in intact rat
      parotid acini. The purpose was to determine the contribution of extracellular
      enzymes in metabolizing ATP and its metabolites. The total enzyme activity
      accounting for extracellular ATP breakdown was at least 75% dependent on added
      divalent cations, consistent with the presence of ectoATPase. Approximately 50%
      of the added ATP was hydrolysed in 1 h by the cells and this percentage was
      independent of cell protein concentration from 80 to 296 micrograms/ml and
      independent of ATP concentration from 4 to 80 microM. ADP. AMP and adenosine were
      identified as metabolites. Cell adenosine uptake was not a factor in controlling
      the levels of extracellular adenosine. Generation of adenosine was limited under
      conditions of higher rates of ATP hydrolysis. Studies in parotid cell membranes
      showed that very little feedback inhibition of ectoATPase was observed. 5'
      Nucleotidase was present at levels of activity of 0.06-0.19 mumol/mg protein/h in
      intact acini. The results confirm the presence of ectonucleotidases which can
      generate ADP, AMP and adenosine. Ectonucleotidase could contribute to reducing
      the effect of extracellular ATP on the parotid cell.

PMID- 9022924
TI  - An immunohistochemical study of regional differences in the distribution of type
      I and type II collagens in rat mandibular condylar cartilage.
AB  - The mammalian temporomandibular joint is a highly specialized diarthrodial joint
      under multidirectional compressive and tensile forces. In such a complicated
      biomechanical environment, the phenotypic expression of extracellular matrix may
      vary in different regions of the mandibular condylar cartilage. To test this
      hypothesis, immunohistochemical techniques were used to examine the localization
      of type I and type II collagens in various anterioposterior regions of the
      condylar cartilage of 4-week-old rats. In the posterosuperior region, which is
      mainly subjected to compressive forces, a strong reaction for type II collagen
      was observed in the cartilaginous layer (maturative and hypertrophic cell
      layers), and a rather weak reaction was observed for type I collagen in the
      precartilaginous and cartilaginous layers, compared with the reactions in other
      peripheral regions. Proceeding anteriorly, staining for type I collagen
      increased, while that for type II collagen decreased. In posteroinferior
      cartilage, which is subjected mainly to tensile forces because of its direct
      attachment to the retrodiscal pad, staining for type I collagen was strong, and
      that for type II collagen was faint in the cartilaginous layer. These results
      demonstrate that marked regional differences exist in the phenotypic expression
      of two major collagen components in mandibular condylar cartilage, which may
      reflect the local functional environment and cellular response.

PMID- 9022925
TI  - Effects of a functional agar surface on in vitro dentinogenesis induced in
      proteolytically isolated, agar-coated dental papillae in rat mandibular incisors.
AB  - In an attempt to study the effects of a three-dimensional agar surface on in
      vitro dentinogenesis both in the growing end and in incisally cross-cut pulp, the
      possible expression of odontoblast phenotype was investigated morphologically,
      autoradiographically and immunohistochemically. Explants were incubated for 8
      days. In the growing end, during the last 4 days, mitotic cells differentiated
      into [3H]-thymidine-labelled, tubular matrix-forming cells. In cross-cut pulp,
      however, during the first 4 days, mitotic cells differentiated into [3H]
      thymidine-labelled, tubular matrix-forming cells. Electron microscopy
      demonstrated that, in both regions, tubular matrix-forming cells had
      characteristics similar to those of primary odontoblasts. When agar was incubated
      alone, exogenous fibronectin was deposited on it rapidly. After 12 h, endogenous
      fibronectin appeared on explant peripheral cells. Collagen and materials reacting
      positively to periodic acid-Schiff (PAS) were first interposed between agar and
      explant after 4 days. After 8 days, an inner immunonegative layer corresponding
      to materials reacting positively to PAS or toluidine blue and an outer
      immunopositive layer of fibronectin or collagen were visible adjacent to the rows
      of elongated columnar cells. In the presence of Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP),
      a competitive inhibitor of attachment of cells to fibronectin, explants became
      detached from the agar surface, and no dentinogenesis occurred. These results
      indicate that, when in contact with an agar surface that becomes modified by
      fibronectin and/or by a complex of fibronectin with deposited matrix, dental
      mesenchymal cells progressively differentiate into tubular matrix-forming cells.
      Possibly the functional agar surface has the important role of providing a
      foothold for cell attachment, which is the first step towards in vitro
      odontoblast differentiation. This system of inducing tubular matrix-forming cells
      constitutes a useful model for the study of in vitro dentinogenesis.

PMID- 9022926
TI  - The distribution of fibronectin and laminin in the murine periodontal membrane,
      indicating possible functional roles in the apical migration of the junctional
      epithelium.
AB  - Periodontal tissue shows various morphological changes with ageing. A typical
      example of these changes is the apical migration of the junctional epithelium.
      The distribution of fibronectin and laminin was investigated by immunofluorescent
      and immunoelectron-microscope methods in mice to clarify any possible functional
      roles of these proteins in the apical migration of junctional epithelium. Apical
      migration begins in 20-week-old mice, and then progresses with increasing age
      until the mice reach 80 weeks. In the apical tip of the junctional epithelium,
      fibronectin was demonstrated in the sub-epithelial fibrillar matrix, preceding
      the progression of apical migration. Fibronectin was also demonstrated in
      association with the stromal side of focal contacts between epithelial cells and
      basement membrane. Therefore, these focal contacts are assumed to be fibronectin
      receptors. There was no apparent relation between the localization of laminin and
      the migration of the junctional epithelium. These results suggest that the
      fibronectin provides a provisional matrix for the apical migration of junctional
      epithelium, but laminin does not appear to play a major part in that migration.

PMID- 9022927
TI  - Genetic heterogeneity of autosomal dominant amelogenesis imperfecta demonstrated
      by its exclusion from the AIH2 region on human chromosome 4Q.
AB  - Amelogenesis imperfecta (AI) is a group of hereditary enamel defects,
      characterized by large clinical diversity. On the basis of differences in
      clinical manifestation and inheritance pattern, 14 different subtypes have been
      recognized. A locus for autosomal dominant AI (ADAI) of local hypoplastic type
      was recently mapped to the region between D4S392 and D4S395 on the long arm of
      chromosome 4. To test whether the chromosome 4 locus is responsible for other
      forms of AI as well, a linkage study was carried out with 17 families
      representing at least five clinical forms of ADAI. Admixture tests for
      heterogeneity performed with the marker D4S2456 gave statistical support for
      genetic heterogeneity of ADAI with the odds 78:1. Linkage to the ADAI locus on
      chromosome 4q (AIH2) could only be demonstrated with families expressing the
      local hypoplastic type, and there was no support for heterogeneity within that
      group of families. Furthermore, linkage could be excluded for five families with
      other clinical forms of ADAI. The data therefore demonstrated that ADAI is
      genetically heterogeneous, and that at least two loci for it exist.

PMID- 9022928
TI  - An immunocytochemical study of the carbonic anhydrase I isoenzyme in human oral
      Merkel cells.
AB  - Merkel cells in human buccal mucosa and hard palate possess the carbonic
      anhydrase I isoenzyme (CAI). CAI colocalized immunocytochemically with a range of
      Merkel cell cytokeratins, namely CK 7, 8, 18, 19 and 20. No other cells in the
      oral epithelium were immunoreactive for the CAI antibody. The presence of the
      enzyme may be related to the function of sensory receptors that produce a
      sustained response to a maintained mechanical stimulus.

PMID- 9022929
TI  - Effect of mechanical removal of the pulp upon the retention of odontoblasts
      around the pulp chamber of human third molars.
AB  - The pulp chambers of 11 freshly extracted human third molars were exposed by
      cutting off the roots apical to the cervical margin and the pulps were either
      removed with forceps and discarded or left in situ. The teeth were fixed,
      demineralized, divided longitudinally, embedded in resin and 2-micron sections
      stained with toluidine blue were examined by light microscopy. In pulp-removed
      specimens the percentage retention of the odontoblast layer with the predentine
      varied near the longitudinal division but when sectioned deeper all six specimens
      displayed 100% retention. The intactness of the retained odontoblast layer was
      mostly good as judged by the mutual close apposition of the distal ends of the
      cell bodies and their relation to the predentine. The retention of the
      odontoblast layer with the predentine may be due to the distribution of
      fibronectin, which others have shown is present between odontoblasts, and between
      odontoblasts and predentine, but lacking beneath the odontoblast layer.

PMID- 9022947
TI  - The measurement of tissue protein turnover.
AB  - Tissue protein turnover can be assessed by a number of semi-, quantitative and
      qualitative methods. There are a number of static indices of the state of
      turnover of protein, for example amount of RNA per DNA or protein, the state of
      aggregation of ribosomes (i.e. the polyribosome index), the abundance of mRNA for
      particular proteins, and the enzymatic activity of proteins such as proteases,
      ribonuclease, etc. In addition, the concentration of particular amino acids such
      as glutamine or non-re-utilizable amino acids, formed post-translationally, such
      as 3-methylhistidine or hydroxyproline, are able to provide snapshot indices.
      However, since turnover is a dynamic process it should, ideally, be probed using
      methods such as the incorporation of tracer amino acids into protein or the
      dilution of tracer amino acids in the free pool by protein breakdown. The
      combination of tracer and tissue or limb balance methods is especially powerful
      since all the dynamic processes can potentially be quantified. The use of stable
      isotopes to label metabolic tracers has dramatically increased the feasibility of
      carrying out measurements of protein synthesis and breakdown and there has been a
      substantial growth in the application of the methods to a wide variety of tissues
      sampled by biopsy or at operation. Summaries of a number of currently feasible
      methods are provided, together with commentary on the relative efficacy of the
      methods and of the instrumental techniques required. There is also a discussion
      of suitable tracer labels and amino acids, plus a summary of the most reliable
      current values for protein turnover in a variety of tissues. The review also
      contains descriptions of potential methods which have not yet been applied in
      human beings but which are feasible, given the current recent increases in the
      accuracy and sensitivity of instrumentation for measurement of stable isotope
      labelling.

PMID- 9022948
TI  - Radiolabelled-tyrosine for the measurement of protein synthesis rate in vivo by
      positron emission tomography.
AB  - The amino acid incorporation rate, generally described as protein synthesis rate
      or PSR, can be assessed in vivo using carboxylic-labelled amino acids such as L
      [1-11C]tyrosine and PET. In animals, labelled tissue metabolites are below 4% of
      total tissue radioactivity and are therefore neglected in the model. Labelled
      plasma metabolites on the other hand rise continuously to 50% of total plasma
      radioactivity at 40 minutes. After correction of the total plasma radioactivity
      for the metabolite fraction, a Patlak analysis may be performed to calculate the
      PSR. A number of applications in the field of oncology were presented. The use of
      L-[1-11C]tyrosine in the study of metabolic disease was also discussed. It is
      concluded that the application of [11C]tyrosine-PET in a clinical setting is of
      interest for an increasing number of diseases.

PMID- 9022949
TI  - The role of substrates in the regulation of protein metabolism.
AB  - Substrates are powerful modulators of amino acid and protein turnover in vivo
      (Table 4). Intravenous infusions of amino acids exert a protein-anabolic effect,
      because they directly inhibit endogenous protein degradation and stimulate
      protein synthesis at the whole-body level. A stimulation of protein synthesis has
      been observed also at the forearm level. These changes resulted in an improvement
      of body and tissue protein balance, which is the ultimate goal of any nutritional
      intervention aimed at preserving body protein stores. In humans acute intravenous
      infusions of carbohydrates do not appear to affect either protein degradation or
      leucine oxidation. However, animal studies support the view that glucose
      availability spares essential amino acids at least in the fetus. The effects of
      hypercaloric refeeding with high-carbohydrate diets may, however, result in
      increased protein turnover. Lipids, in the form of long-chain fatty acids,
      inhibit endogenous protein breakdown and may suppress leucine oxidation in the
      whole body. They do not affect protein synthesis. In contrast, medium-chain fatty
      acids apparently increased leucine oxidation, and therefore increased net protein
      catabolism. Ketone bodies may be anabolic provided that fatty acid concentrations
      are not concurrently decreased.

PMID- 9022950
TI  - Post-prandial protein metabolism.
AB  - Current post-prandial studies of amino acid metabolism and utilization are
      consistent with a feeding mechanism mediated primarily by insulin and amino
      acids, with the balance between protein conservation and net deposition dependent
      on the amino acid supply [1-13C]leucine post-prandial kinetic tracer studies of
      leucine oxidation, non-oxidative disappearance and endogenous appearance allow
      study of the regulation of whole-body amino acid oxidation, protein synthesis and
      proteolysis. On the basis of these studies it appears that for leucine oxidation,
      the main determinant of the efficiency of protein utilization, the overriding
      regulatory influence is substrate availability rather than insulin. Such
      substrate sensitivity is manifest throughout the physiological range of insulin
      down to the lowest insulin levels observed suggesting that a basal insulin need
      is not an important part of regulation of this important catabolic pathway. The
      key protein turnover response is an inhibition of proteolysis sufficient to limit
      any increases in amino acid levels thus limiting any increase in amino acid
      oxidation. It appears that the influences of amino acids and insulin on
      proteolysis are separate and additive and may both be receptor mediated so that
      extracellular amino acid levels can regulate intracellular levels. It is likely
      that protein synthesis is regulated by intracellular amino acid levels but post
      prandial stimulation through increases in amino acid levels appears to be
      unhelpful because of parallel increases in amino acid oxidation. Evidence for any
      influence of insulin on protein synthesis has yet to be unequivocally identified.

PMID- 9022951
TI  - The hormonal control of protein metabolism.
AB  - While all the hormones described have regulatory effects on the rates of protein
      synthesis and breakdown there is a complex interaction between them in this
      control process. Insulin, GH and IGF-I play a dominant role in the day-to-day
      regulation of protein metabolism. In humans insulin appears to act primarily to
      inhibit proteolysis while GH stimulates protein synthesis. In the post-absorptive
      state IGF-I has acute insulin-like effects on proteolysis but in the fed state,
      or when substrate is provided for protein synthesis in the form of an amino acid
      infusion, IGF-I has been shown to stimulate protein synthesis. Growth hormone and
      testosterone have an important role during growth but continue to be required to
      maintain body protein during adulthood. Thyroid hormones are also required for
      normal growth and development. The hormones glucagon, glucocorticoids and
      adrenaline are all increased in catabolic states and may work in concert to
      increase protein breakdown in muscle tissue and to increase amino acid uptake in
      liver for gluconeogenesis. While increased glucocorticoids result in reduced
      muscle mass the effects of glucagon may be predominantly in the liver resulting
      in increased uptake of amino acids. In contrast to the catabolic effect of
      adrenaline on glucose and lipid metabolism, studies to date suggest that
      adrenaline may have an anti-catabolic effect on protein metabolism. Despite this
      adrenaline increases the production of the gluconeogenic amino acid alanine by
      muscle and its uptake by the splanchnic bed. There is considerable interest in
      the use of anabolic hormones, either alone or in combination, in the treatment of
      catabolic states. GH combined with insulin has been shown to improve whole-body
      and skeletal muscle kinetics while GH combined with IGF-I has a greater positive
      effect on protein metabolism in catabolic states than either hormone alone. If
      catabolic states are to be treated successfully a greater understanding of the
      role of the catabolic hormones in these states and the possible treatment of
      these states with anabolic hormones is required.

PMID- 9022952
TI  - Protein metabolism in pregnancy.

PMID- 9022953
TI  - Protein metabolism in diabetes mellitus.
AB  - Insulin deficiency is a protein catabolic state. In vivo studies have shown that
      insulin enhances short-side-chain amino acid intracellular uptake, stimulates
      transcription and translation of RNA, increases the gene expression of albumin
      and other proteins and inhibits liver protein breakdown enzymes. In IDDM patients
      most of the whole-body protein turnover studies have shown that insulin
      deficiency increases protein breakdown and increases amino acid oxidation and
      that these effects are reversed by insulin treatment. Recent studies have
      demonstrated that a substantial increase in leucine transamination during insulin
      deprivation contributes to leucine catabolism in IDDM patients. Protein synthesis
      in the insulin-deprived state is also increased although to a lesser extent than
      protein breakdown, and this increased whole-body protein synthesis is reduced
      with an insulin infusion; thus the effects of insulin are largely mediated
      through its effects on protein breakdown. The metabolic derangements in diabetes
      frequently involve disturbances in substrates and hormones other than insulin.
      The observed effects of insulin deficiency in diabetic patients vary in different
      body compartments; most of the effects of insulin on protein synthesis appear to
      occur in non-muscular tissues especially in the splanchnic area. In addition,
      insulin has a differential effect on hepatic protein synthesis, i.e. inhibits
      fibrinogen synthesis and promotes albumin synthesis. Insulin's anticatabolic
      effect in IDDM patients is largely due to its inhibition of protein breakdown.
      The net protein anabolism due to insulin occurs largely in skeletal muscle. In
      patients with NIDDM these effects are not noted, presumably because of residual
      endogenous insulin secretion. In fact, treatments that result in improvement of
      glucose metabolism in obese NIDDM patients do not affect protein metabolism.

PMID- 9022954
TI  - Protein metabolism in critical illness.
AB  - In summary, protein metabolism of critically ill patients is a field open to new
      investigations that will help us to understand better the mechanism behind
      'autocannibalism', which is still today associated with mortality. Although the
      underlying disease is the major determinant of mortality, nutritional depletion
      will add morbidity, an addition that grows over time in the ICU. With
      conventional treatment the velocity of the catabolic process can at best be
      slowed down and the patient be bought time for other types of treatment to work.
      New forms of specific nutrition and adjuvant therapies may give us tools to
      prevent muscle depletion, without endangering the supply of essential substrates
      to the tissues in the splanchnic area. Muscle is at present a limiting organ for
      the ICU patient in two respects. A depleted muscle can no longer provide enough
      substrates for the splanchnic organs to maintain intestinal integrity and to
      maintain a high immunocompetence. In addition, a depleted muscle will be restored
      back to normal only very slowly; in elderly patients restoration may not even
      occur at all. The effects of an attenuation of muscle depletion on rehabilitation
      time have yet to be evaluated. An understanding of protein metabolism may be the
      key to better patient care in the ICU in the future.

PMID- 9022955
TI  - Protein metabolism and liver disease.
AB  - In health, the liver orchestrates the metabolism of proteins and amino acids.
      When the liver is diseased, the regulation of protein metabolism is frequently
      disturbed. The manifestations of disturbed protein metabolism in liver disease
      are varied and change with disease aetiology and severity. The hallmarks of
      protein and amino acid metabolism in liver disease are lowered concentrations of
      circulating branched-chain and increased concentrations of circulating aromatic
      amino acids with concomitantly altered amino acid kinetics. The changes in amino
      acid kinetics in liver disease are characterized by increased endogenous leucine
      flux, an indicator of protein breakdown, and leucine oxidation in the post
      absorptive state (when calculated using a reciprocal-pool model and normalized
      for body cell mass). In addition, the increase in whole-body protein synthesis in
      response to an amino acid infusion may be attenuated in patients with cirrhosis.
      These changes are often accompanied by clinically apparent muscle wasting,
      manifest as protein-calorie malnutrition, and associated low levels of
      hepatically synthesized plasma proteins. While the pathogenesis of these changes
      in protein and amino acid metabolism has not been elucidated, altered levels of
      circulating hormones, known to affect protein metabolism, are probably important.
      Lowered levels of micronutrients and trace metals and elevated levels of
      cytokines may also play a role.

PMID- 9022956
TI  - Methods for the treatment of collagenous tissues for bioprostheses.
AB  - Collagenous tissue as a biomaterial possesses many favourable characteristics and
      advantages over synthetic materials. The resemblance to human tissue suggests
      that it has a performance advantage over alternative materials. This advantage
      has been exploited to produce clinical devices that have been implanted in
      patients for more than a quarter of a century. The method of treating collagenous
      tissue for bioprostheses has developed from crude exposure of tissue to chemicals
      to a sophisticated level of considering the biochemical, chemical, engineering
      and clinical aspects of the process. This review focuses on the various chemical
      and physical treatments that have made the bioprostheses possible, highlighting
      the chemical agents and the cross-linking mechanism involved.

PMID- 9022957
TI  - Vascular endothelial cell responses to different electrically charged
      poly(vinylidene fluoride) supports under static and oscillating flow conditions.
AB  - We investigated the effect of electrically charged surface copolymers on
      endothelialization of four types of poly(vinylidene fluoride) (PVDF) copolymer
      surface films with different electrical characteristics. PVDF films without a
      surface charge, with a remanent surface (5 and 7 microC) and with piezoelectric
      characteristics were studied through the secretion by an endothelial cell (EC)
      line culture, under static and oscillating flow conditions of prostacyclin (PGI2)
      and thromboxane (TXA2), two metabolites which have directly opposing actions on
      platelet function. The surface electrical properties of PVDF are suitable for
      promoting cell adhesion. Secretion of thrombomodulatory mediators varied,
      depending on the surface electrical charge and on the molecular structure of the
      PVDF substrate. Under static conditions the ECs respond to the substrates by a
      similar increase of PGI2. Under oscillating flow conditions, the ratio of PGI2 to
      TXA2 is higher with the piezoelectric PVDF film. The piezoelectricity generated
      from shear stress along the entire length of the fibres may be appropriate in
      vivo to keep the [PGI2]/[TXA2] ratio at a level which could counteract the build
      up of surface deposits which could be at the origin of thrombosis.

PMID- 9022958
TI  - Vascugraft polyurethane arterial prosthesis as femoro-popliteal and femoro
      peroneal bypasses in humans: pathological, structural and chemical analyses of
      four excised grafts.
AB  - Following positive results obtained in in vitro studies and in vivo implantations
      in animals, a clinical trial using the Vascugraft polyurethane arterial
      prosthesis as a below-knee substitute was undertaken in 15 patients. Eight grafts
      became occluded during the first year, and segments from four of them were
      explanted and made available for pathological, structural and chemical
      investigations. The implantation periods ranged from 21 to 358 days. Failures
      were associated with kinking (one case), possible anastomotic mismatch between
      the graft and the artery (one case), and poor run-off (two cases). No organized
      collagenous internal encapsulation was noted; however, endothelial-like cells
      were observed at the anastomotic site of one graft. No significant structural
      degradation of the prostheses was observed in those grafts implanted for 21, 38
      and 46 days. Some deteriorations in the fibrous structure were observed on the
      external surface of the prosthesis implanted for 358 days. High-resolution carbon
      C1s analysis by ESCA demonstrated a 60 to 80% decrease in carbonate content on
      the surface of all explanted prostheses. Chemical analyses of each polyurethane
      graft by IR, SEC and DSC revealed no significant chemical changes. The clinical
      performance of the Vascugraft prosthesis for below-knee implantation proved to be
      no more impressive than that of expanded polytetrafluorethylene, the currently
      accepted reference. The decision by B. Braun Melsungen AG to end this program is
      therefore to be regarded as highly professional.

PMID- 9022959
TI  - Surface characterization of poly(alpha-hydroxy acid) microspheres prepared by a
      solvent evaporation/extraction process.
AB  - This work constitutes the first attempt to characterize the wettability of
      poly(alpha-hydroxy acid) (PAHA) microspheres in situ, prepared according to a
      complex process involving emulsification, solvent evaporation, washing and freeze
      drying. The analysis of the flotation profile of the microspheres has allowed us
      to determine both advancing and receding contact angles at the
      microsphere/air/water interface and furnished information on the organization of
      poly(vinyl alcohol) (PVA) and bovine serum albumin (BSA) at the surface of the
      PAHA coating. By the comparison of contact angles measured from model surfaces
      obtained by sampling pure PAHA, PVA, BSA and mixed PVA/PAHA monolayers on glass
      and poly(methyl methacrylate) (PMMA) substrates, it was concluded that the
      emulsifier (PVA or BSA) was strongly anchored to the surfaces of the
      microspheres. The use of BSA to formulate the microspheres from a single oil-in
      water emulsion led to dry particles having a hydrophobic surface. The unfolding
      of the hydrophilic segments of the BSA embedded at the surface of the
      microspheres, following immersion in water, increased the wettability of the
      microspheres by water. The same qualitative results were obtained when PVA was
      used to stabilize single emulsions. On the other hand, microspheres formulated
      from a double water-in-oil-in-water emulsion displayed no modifications of their
      wettability when immersed in water. This can be explained by the absence of
      mobility of the hydrophilic segments of the emulsifier which are blocked in the
      surface or at the subsurface of the polymer matrix.

PMID- 9022960
TI  - Histological evaluation of the biocompatibility of a glass-ionomer cement in rat
      alveolus.
AB  - A type III glass-ionomer cement (Vidrion F), currently used as fast-setting
      lining material and fissure sealant, was implanted into rat dental alveolus
      immediately after tooth extraction and its biocompatibility was analysed in terms
      of incorporation into alveolar bone in the wound healing process. Histological
      and histometric evaluation of trial areas adjacent to the implants showed that by
      week 1 the glass-ionomer granules were encircled by a conspicuous capsule
      surrounded by immature connective tissue. By week 3 the implants were surrounded
      by a less prominent fibrous capsule and most of the tested area was occupied by
      mature trabecular bone. By week 6 the fibrous capsule was thinner and the tested
      area was almost totally covered by bone, which was in close contact with the
      implanted material in several places. Quantitative data confirmed progressive new
      bone formation in parallel with a decrease in the percentage fraction of
      connective tissue in the trial areas around the implants. The results revealed
      that the tested material is biologically compatible, being progressively
      incorporated into alveolar bone in the wound healing process. The quantitative
      evaluation of alveolar wound healing around a glass-ionomer implant may provide
      an experimental model for future comparative studies carried out with other
      biomaterials.

PMID- 9022961
TI  - Dynamic compaction: a new process to compact therapeutic agent-loaded calcium
      phosphates.
AB  - The sintering stage in the classical process of preparing bone substitution
      materials prevents therapeutic agents from being loaded into calcium phosphate
      powder. However, dynamic compaction, a new process, requires no external heat,
      allowing the therapeutic agent to be incorporated into ceramics. This report
      presents the results of an in vitro study of therapeutic agents associated with
      calcium phosphate powder and involving this new process. A mixture of vancomycin
      lyophilized powder (0.15 g) and biphasic calcium phosphate (BCP) powder (1.85 g)
      was compacted. In addition, 2 ml of human growth hormone (1 mg ml-1) were
      associated with BCP powder by physical adsorption on bead surfaces before
      compaction. Detection by monoclonal antibodies and sodium dodecyl sulphate
      polyacrylamide gel electrophoresis demonstrated the structural integrity of the
      two therapeutic agents after consolidation. This new compaction process should be
      useful in developing ceramics that contain a therapeutic agent.

PMID- 9022963
TI  - Composite titanium dental implant fabricated by electro-discharge compaction.
AB  - An electro-discharge compaction (EDC) fabrication window was established for
      producing commercially pure porous titanium dental implants of 4 mm diameter and
      7 mm length with a solid titanium cap. The optimum input energy was in the range
      of 0.58-0.87 kJ g-1 for a powder column of 0.500 g. Input energy greater than
      0.58 kJ g-1 resulted in an implant torque strength exceeding 30 N-cm (the
      retaining screw tightening torque), while input energy greater than 0.72 kJ g-1
      exceeded 46.7 N-cm torque strength (at this level the retaining screw failed
      prior to the implant). The integrity of the internally threaded hole and
      hexagonal head of the cap were maintained throughout the EDC process. The EDC
      process did not after the strength and/or microstructure of the components, and
      the bead-cap interface was stronger than the bead-bead interface. EDC implants
      produced within the aforementioned window have sufficient compressive strengths
      and other physical properties to meet the requirement for titanium dental
      implants.

PMID- 9022962
TI  - In vivo study of a calcium phosphate cement consisting of alpha-tricalcium
      phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide.
AB  - Prehardened calcium phosphate cement consisting of alpha-tricalcium phosphate
      (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate
      monoxide (TeCP) was implanted in rabbit mandibles and back muscles, and studied
      histologically and microradiographically. In the mandibles, new bone formation
      occurred around the implants and increased in quantity the longer the implant
      period lasted. Histology, microradiography and scanning electron microscopy (SEM)
      demonstrated direct contact of bone and cement. Bone response to this cement was
      essentially the same as to hydroxyapatite (HA) ceramics, known as a biocompatible
      bone substitute. Material resorption was recognized, which increased with the
      implant period and was greater in the surface bound by soft tissue than the
      surface bound by bone tissue. In the back muscles, however, no calcified tissue
      formation occurred. Resorption proved to be faster than in the case of the
      mandible implants. It was concluded that the cement, in prehardened form, has
      good biocompatibility and is a promising material as a bone substitute.

PMID- 9022964
TI  - Wound healing phenomena in titanium fibre mesh: the influence of the length of
      implantation.
AB  - In previous experiments a new type of percutaneous device for implantation in
      soft tissue was designed, containing a sintered titanium fibre mesh. The devices
      are inserted by a so-called "two-phase' surgical technique with an intervening
      healing period of 3 months between insertion of the subcutaneous and percutaneous
      parts. From a clinical point of view, this time interval is too long. The aim of
      this study was to investigate whether it was possible to reduce the intervening
      healing period. The implants were inserted in the backs of nine goats. In each
      goat, six implants were placed with intervals of 1 week. Consequently, at the end
      of the experiment, in each goat six implants were present with implantation
      periods ranging from 1 to 6 weeks. After 6 weeks, the animals were killed and the
      implants with surrounding tissue were processed histologically. Analysis
      demonstrated that during the first 2 weeks an inflammatory response was present.
      Thereafter, no difference in tissue response was found between the various
      implantation periods. In conclusion, the experiment suggests that for titanium
      mesh percutaneous devices a 3-week healing period is sufficient between the
      installation of the subcutaneous and percutaneous parts.

PMID- 9022965
TI  - Photo-immobilization of dipyridamole (Persantin) at the surface of polyurethane
      biomaterials: reduction of in-vitro thrombogenicity.
AB  - Dipyridamole is a well-known vasodilator and a powerful inhibitor of activation
      and aggregation of blood platelets. Moreover, dipyridamole is essentially non
      toxic. The drug is used extensively in clinical anti-coagulation regimes, for
      example pre- and post-coronary angioplasty procedures. Recently, we have found
      that photochemical, covalent coupling of dipyridamole to polyurethane surfaces
      leads to improved thromboresistance in vitro. This phenomenon is now studied in
      more detail. Both qualitative and more quantitative biochemical experiments were
      performed in order to characterize the in vitro blood compatibility of a set of
      polyurethane surfaces onto which dipyridamole was immobilized. First, scanning
      electron microscopy was used to examine the morphology of platelets which adhered
      during incubation with platelet-rich plasma. These experiments showed that
      immobilization of dipyridamole leads to a clearly decreased number of adherent
      platelets and to a largely diminished propensity of the surface to activate
      adherent platelets. Secondly, an in vitro thrombogenicity assay was run. These
      experiments showed that the thromboresistance increased with increasing surface
      density of immobilized dipyridamole. A short spacer chain separating dipyridamole
      from the polymer surface, was found to improve the thromboresistance further.
      Such a spacer chain apparently increases the efficacy of the immobilized drug.
      Collectively, the present results further substantiate the idea that dipyridamole
      retains its inhibitory activity with respect to activation and aggregation of
      blood platelets, when the compound is covalently attached to a polymer surface.
      The possible utility of these findings with respect to the development of an
      artificial blood vessel prosthesis is discussed briefly.

PMID- 9022966
TI  - Fabrication of microcapsules using poly(ethylene adipate) and a blend of
      poly(ethylene adipate) with poly(hydroxybutyrate-hydroxyvalerate): incorporation
      and release of bovine serum albumin.
AB  - Spherical reservoir-type microcapsules composed of poly(ethylene adipate) (PEAD)
      and 20% poly-epsilon-caprolactone (PCL II), poly(hydroxybutyrate-hydroxyvalerate)
      (P(HB-HV)); 10.8% HV) 20% PCL II and a blend of P(HB-HV)/PEAD 20% PCL II
      containing bovine serum albumin (BSA; surrogate protein)-loaded agarose have been
      fabricated using a double emulsion technique with solvent evaporation. P(HB-HV)
      and PEAD microcapsules had microporous and smooth surfaces, respectively, while
      blend microcapsules contained a mixture of the two. Irrespective of the
      fabrication polymer, microcapsules were generated in high yield (> 75%) and BSA
      incorporation had no significant effect on microcapsule size distribution (8-200
      microns). The loss of BSA, both by partitioning into aqueous continuous phase and
      through the micropores of P(HB-HV) microcapsules as BSA-loaded agarose during the
      precipitation of the fabrication polymer concomitant with solvent evaporation,
      resulted in low encapsulation efficiencies (< 15%). In all cases BSA release
      could be monitored for up to 26 d and the amount and duration of BSA release from
      P(HB-HV) 20% PCL II microcapsules was influenced as much by micropore number and
      diameter as by the extent of reservoir loading, while BSA release from smooth
      PEAD microcapsules was assumed to be the result of an acute increase in membrane
      porosity.

PMID- 9022967
TI  - Release of residual methyl methacrylate into water from glass fibre-poly(methyl
      methacrylate) composite used in dentures.
AB  - The aim of this study was to determine the release of residual methyl
      methacrylate (MMA) into water from heat-cured and chemical-cured test specimens
      of continuous glass fibre-poly(methyl methacrylate) (PMMA) composite fabricated
      from experimental glass fibre reinforcement. The glass fibre concentration of the
      test specimens was 12% by weight. The residual MMA was extracted from the storage
      water of the test specimens (n = 5 per group) and its concentration was
      determined by high-performance liquid chromatography. The results revealed that
      release of residual MMA from heat-cured test specimens with glass fibre
      reinforcement was significantly higher than that from unreinforced test specimens
      (P = 0.003), while in chemical-cured test specimens with and without glass fibre
      reinforcement the amount of MMA released did not differ (P = 0.501). In general,
      however the test specimens made from chemical-cured PMMA released more residual
      MMA than specimens made from heat-cured PMMA (P < 0.001). This study suggests
      that the use of glass fibre reinforcement in heat-cured denture PMMA
      statistically increases the release of residual MMA from the material, but it is
      questionable whether it has clinical significance.

PMID- 9022968
TI  - Properties of triple helix formation with oligodeoxyribonucleotides containing 8
      oxo-2'-deoxyadenosine and 2'-modified nucleoside derivatives.
AB  - The ability of homopyrimidine oligonucleotides containing 8-oxo-2'-deoxyadenosine
      (dAOH), 2'-methoxyuridine (Um), 2'-fluorouridine (Uf), 2'-methoxycytidine (Cm),
      and 2'-fluorocytidine (Cf) to form stable, triple-helical structures with
      sequences containing the recognition site for the class II-S restriction enzyme,
      Ksp632-I, was studied as a function of pH. The 8-oxo-2'-deoxyadenosine
      substituted oligomers were shown to bind within the physiological pH range in a
      pH-independent fashion, without a compromise in specificity. In particular, the
      substitutions of three deoxycytidine residues with 8-oxo-2'-deoxyadenosine showed
      higher endonuclease inhibition than the substitution of either one or two
      deoxycytidine residues with 8-oxo-2'-deoxyadenosine. In contrast, the
      oligonucleotides containing 2'-modified nucleosides (Uf, Um, Uf-Cf, Um-Cm, dAOH
      Uf, and dAOH-Um) bind in a pH-dependent manner to the target duplex.

PMID- 9022969
TI  - An efficient synthesis of methyl tetra-O-hexyl gentiooctaoside, an octaosyl
      analogue of ANP receptor antagonist HS-142-1.
AB  - Methyl 0-(3-0-hexyl-beta-D-glucopyranosyl)-(1->6)-[0-(beta-D-glucopyranosyl)-(1 
      >6)-0-(3-0-hexyl-beta-D-glucopyranosyl)-(1->6)3-beta-D- glucopyranoside, a 3-0
      hexyl analogue of the octaosyl component of fungal lipooligosaccharide HS-142-1,
      was stereo- and regioselectively synthesized as a potent antagonist for the
      tetrameric atrial natriuretic peptide (ANP) receptors.

PMID- 9022970
TI  - Slow reversible inhibitions of rabbit muscle aldolase with substrate analogues:
      synthesis, enzymatic kinetics and UV difference spectroscopy studies.
AB  - Various dihydroxyacetone-phosphate (DHAP) analogues bearing an aromatic ring or
      beta-dicarbonyl structures were synthesized. Their capacity to form a stabilized
      iminium ion or conjugated enamine in the reaction catalyzed by rabbit muscle
      aldolase (EC 4.1.2.13) were investigated by enzymatic kinetics and UV difference
      spectroscopic techniques. Whereas the aromatic derivative led to competitive
      inhibition without detectable iminium ion formation, slow reversible inhibitions
      of aldolase by beta-dicarbonyl compounds was shown to have taken place.
      Conjugated enamine formation at the active site of the enzyme was detected by
      their specific absorbances close to 317 nm.

PMID- 9022972
TI  - Synthesis, NMR spectroscopy study, and antimuscarinic activity of a series of 2
      (acyloxymethyl)-1,3-dioxolanes.
AB  - A series of 1,3-dioxolane-based ligands, bearing hydroxymethyl or ester
      functionalities, was synthesized and tested as potential muscarinic antagonists.
      The compounds display moderate to low affinity for the three receptor subtypes M1
      M3, with some of them showing a significant selectivity for the M3 subtype. The
      configurational and conformational properties were studied using NOE experiments
      and vicinal coupling constants. The 1H and 13C NMR chemical shifts show
      stereochemically dependent trends. Quantitative analysis of conformer populations
      showed that the exocyclic CH2N CH3)3 group is prevalently in a pseudo-axial
      orientation in the cis isomers and in a pseudo-equatorial orientation in the
      trans isomers.

PMID- 9022971
TI  - C2-symmetrical tetrahydroxyazepanes as inhibitors of glycosidases and HIV/FIV
      proteases.
AB  - C2-Symmetrical tetrahydroxyazepanes were synthesized as inhibitors for
      glycosidases. Tetrahydroxyazepane 1 is a non-specific inhibitor of various
      glycosidases, while compounds 2, 3 and 4 specifically inhibit beta-N
      acetylglucosaminidase, beta-glucosidase, and alpha-fucosidase, respectively, with
      Ki in the micromolar range. Compound 1 is not an inhibitor of HIV/FIV proteases,
      but its 3,6-difluorobenzyl derivatives are moderate inhibitors of both enzymes.

PMID- 9022973
TI  - Hexose keto-C-glycoside conjugates: design, synthesis, cytotoxicity, and
      evaluation of their affinity for the glucose transporter Glut-1.
AB  - The design, synthesis, cytotoxicity, and biological evaluation of carbohydrate/C
      glycoside conjugates are described. The design concept is predicted on the idea
      that physiological barriers like the blood brain barrier could be crossed
      selectively by using glucose or glucose derivative/drug conjugates. The study
      demonstrates that, (1) carbohydrates and C-glycosides can be bonded at
      nonanomeric positions by the reaction of carbohydrate triflates with C-glycoside
      alkoxydes in the presence of DMPU; (2) there is a structure-activity relationship
      between the cytotoxicity of the conjugate and the nature of the carbohydrate
      residue; and (3) peracetylated hexose keto-C-glycoside conjugates are the most
      cytotoxic keto-C-glycosides.

PMID- 9022974
TI  - Structure-activity relationships of 2-aryl-2,5-dihydropyridazino [4,3-b]indol
      3(3H)-ones at the benzodiazepine receptor.
AB  - A large series of 2-aryl-2,5-dihydropyridazino[4,3-b]indol-3(3H)ones (PIs)
      carrying properly selected substituents at the indole and N2-phenyl rings was
      prepared and tested as central benzodiazepine receptor (BZR) ligands and
      potential (anti)convulsant agents. Stereoelectronic requirements for high
      receptor affinity were detected by means of 2-D and 3-D QSAR analyses. BZR
      affinities and pharmacological profiles of the compounds were examined in
      comparison with some other pyridazinoindolones recently described by us and with
      pyrazoloquinoline (PQ) analogues. An anticonvulsant activity greater than PQs was
      generally observed for PIs. Notably, in the test of audiogenically induced
      seizures, one compound showed a potency comparable to that of diazepam.

PMID- 9022975
TI  - The anticonvulsant activities of functionalized N-benzyl 2-acetamidoacetamides.
      The importance of the 2-acetamido substituent.
AB  - Recent studies have demonstrated that substituted N-benzyl 2-acetamidoacetamides
      provide significant protection against maximal electroshock (MES)-induced
      seizures in mice and rats. In this study, we investigated whether the 2-acetamido
      moiety was necessary for anticonvulsant activity. Ten derivatives of the known
      anticonvulsant, N-benzyl 2-acetamido-2-phenyl-acetamide were prepared in which
      the 2-acetamido group was replaced by hydrogen, methyl, oxygen, and halogen
      substituents. Evaluation of these compounds in the MES-induced seizure test
      demonstrated that both the hydroxy and the methexy compounds provided full
      protection against MES-induced seizures in mice given ip at 100 mg/kg. Moreover,
      evaluation of the individual stereoisomers for the hydroxy compound showed that
      the principal activity resided in the (R)-isomer. These findings demonstrated
      that the 2-acetamido substituent is important but not obligatory for the
      prevention of MES-induced seizures. Further supporting evidence was provided by
      comparing the pharmacological activities of N-benzyl 2,3-dimethoxypropionamide
      with N-benzyl 2-acetamido-3-methoxypropionamide. The ED50 value for the former in
      the MES test was 30 mg/kg (i.p.), which compared favorably with phenobarbital
      (ED50 = 22 mg/kg), but the ED50 value for N-benzyl 2-acetamido-3
      methoxypropionamide was 8.3 mg/kg.

PMID- 9022976
TI  - Non-peptidic inhibitors of human neutrophil elastase: the design and synthesis of
      sulfonanilide-containing inhibitors.
AB  - A novel series of pivaloyloxy benzene derivatives has been identified as potent
      and selective human neutrophil elastase (HNE) inhibitors. Convergent syntheses
      were developed in order to identify the inhibitors which are intravenously
      effective in an animal model. A compound of particular interest is the
      sulfonanilide-containing analogues. Structure-activity relationships are
      discussed. Structural requirements for metabolic stabilization are also
      discussed.

PMID- 9022977
TI  - Synthesis and structure-activity relationships of cephalosporins, 2-isocephems,
      and 2-oxaisocephems with C-3' or C-7 catechol or related aromatics.
AB  - A series of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' catechol
      containing (pyridinium-4-thio)methyl groups and 2-isocephems with C-7 catechol
      related aromatics have been prepared and evaluated for antimicrobial activity. It
      turns out that these compounds have highly potent activity against Gram-negative
      bacteria, especially resistant pathogens such as Pseudomonas aeruginosa. The most
      active compound of the series was (6S,7S)-7-[2-(2-aminothiazol-4-yl)-2-[(Z)-[(1,5
      dihydroxy-4-pyr idon-2-yl) methoxy]imino]acetamido]-3-[[[(4-methyl-5
      carboxymethyl)thiazol-2- yl] thio]methyl]-8-oxo-1-aza-4-thiabicyclo [4.2.0] oct-2
      ene-2-carboxylic acid which exhibited potent in vitro activity against clinically
      isolated P, aeruginosa and Acinetobacter baumanii which is also resistant to many
      anti-infectives, and good in vivo efficacy against clinically isolated P
      aeruginosa.

PMID- 9022978
TI  - Ligand recognition in mu opioid receptor: experimentally based modeling of mu
      opioid receptor binding sites and their testing by ligand docking.
AB  - For three-dimensional understanding of the mechanisms that control potency and
      selectivity of the ligand binding at the atomic level, we have analysed opioid
      receptor-ligand interaction based on the receptor's 3D model. As a first step, we
      have constructed molecular models for the multiple opioid receptor subtypes using
      bacteriorhodopsin as a template. The S-activated dihydromorphine derivatives
      should serve as powerful tools in mapping the three-dimensional structure of the
      mu opioid receptor, including the nature of the agonist-mediated conformational
      change that permits G protein-coupling to "second messenger' effector molecules,
      and in identifying specific ligand-binding contacts with the mu opioid receptor.
      The analyses of the interactions of some opioid ligands with the predicted ligand
      binding sites are consistent with the results of the affinity labeling
      experiments.

PMID- 9022979
TI  - Tachykinin NK-1 receptor probed with constrained analogues of substance P.
AB  - The action of rotameric probes introduced either in position 7 or 8 in the
      sequence of substance P (SP) was investigated, i.e. L-tetrahydroisoquinoleic acid
      (Tic), L-fluorenylglycine (Flg), L-diphenylalanine (Dip), the diastereoisomers of
      L-1-Indanylglycine (Ing) and L-benz[f]indanylglycine (Bfi), the Z- and E-isomers
      of dehydrophenylalanine and dehydronaphthylalanine (delta ZPhe, delta EPhe, delta
      ZNal, ENal) and L-O,O'-dimethylphenylalanine (Dmp). The aim of this study was the
      topographical characterization of the binding subsites of human NK-1 receptor
      expressed in CHO cells, especially the S7 and S8 subsites, corresponding to
      residues Phe7 and Phe8 of substance P. According to the binding potencies of
      these substituted-SP analogues, the S7 binding subsite is smaller than the S8
      subsite: the S7 subsite accepts only one aromatic nucleus, while the S8 can
      accommodate three coplanar nuclei altogether. These findings are compatible with
      the idea that the S8 binding subsite may reside in the extracellular loops of the
      hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the
      production of both inositol phosphates and cyclic AMP. As already quoted for
      septide, [pGlu6, Pro9]SP(6-11), discrepancies are observed between affinity (K1)
      and activity (EC50) values for IPs production. While a weak correlation between
      K1 and EC50 values for IPs production could be found (r = 0.70), an excellent
      correlation could be demonstrated between their affinities (K1) and their
      potencies (EC50) for cAMP production (r = 0.97). The high potency (EC50) observed
      for "septide-like' molecules on PI hydrolysis, compared to their affinity is not
      an artefact related to the high level of NK-1 receptors expressed on CHO cells
      since a good correlation was found between EC50 values obtained for PI hydrolysis
      and those measured for spasmogenic activity in guinea pig ileum bioassay (r =
      0.94).

PMID- 9022981
TI  - Synthesis and biological evaluation of 2-amino-2-deoxy- and 6-amino-6-deoxy
      cyclomaltoheptaose polysulfates as synergists for angiogenesis inhibition.
AB  - 2-Amino-2-deoxy-cyclomaltoheptaose was prepared from beta-cyclodextrin
      perbenzoate [heptakis(2,3,6-tri-O-benzoyl)cyclomaltoheptaose] by a series of
      reactions including selective de-O-benzoylation at C-2 of one of the
      perbenzoylated D-glucopyranosyl moieties, oxidation to the 2-ulose derivative,
      oxime formation, and reduction to the 2-amino-2-deoxy-D-glucose moiety. This
      compound and 6-amino-6-deoxycyclomaltoheptaose accessible from beta-cyclodextrin
      through the known procedure were sulfated to give polysulfated
      aminocyclomaltoheptaose derivatives (3, 5). Employing beta-cyclodextrin
      polysulfate as a reference compound, the synergistic effects of 3 and 5 for
      cortexolone or angiogenesis inhibitory activity were examined by rabbit-corneal
      micropocket assay system. In contrast to the significant anti-angiogenesis
      activity of the beta-cyclodextrin polysulfate-cortexolone pair, neither 3 nor 5
      showed any cooperative activity with cortexolone in the inhibition of basic FGF
      induced angiogenesis.

PMID- 9022980
TI  - Enzymatic synthesis of S-adenosyl-L-methionine on the preparative scale.
AB  - The problems inherent in the enzymatic and chemical synthesis of S-adenosyl-L
      methionine (SAM) led us to develop an efficient, simple method for the synthesis
      of large amounts of labeled SAM. Previously, we reported that the problem of
      product inhibition of E. coli SAM synthetase encoded by the metK gene was
      successfully overcome in the presence of sodium p-toluenesulfonate (pTsONa). This
      research has now been expanded to demonstrate that product inhibition of this
      enzyme can also be overcome by adding a high concentration of beta
      mercaptoethanol (beta ME), acetonitrile, or urea. In addition a recombinant
      strain of E. coli has been constructed that expresses the yeast SAM synthetase
      encoded by the sam2 gene. The yeast enzyme does not have the problem of product
      inhibition seen with the E. coli enzyme. Complete conversion of 10 mM methionine
      to SAM was achieved in incubations with either the recombinant yeast enzyme and 1
      molar potassium ion or the E. coli enzyme in the presence of additives such as
      beta ME, acetonitrile, urea, or pTsONa. The recombinant yeast SAM synthetase was
      used to generate SAM in situ for use in the multi-enzymatic synthesis of
      precorrin 2.

PMID- 9022983
TI  - Use of BOP-Cl in the presence of Boc-amino monothioacids for the thioacylation of
      imino acid residues.
AB  - BOP-Cl was found to be an efficient coupling reagent for the introduction of
      thiopeptide bonds on imino acid residues (Pro, Sar). Boc-amino monothioacids were
      coupled at moderate temperature (0 degree C-RT) with fair yields and with
      retained optical purity. The mechanism of the coupling reaction is discussed.

PMID- 9022982
TI  - Muscarinic thioligands with cyclopentane nucleus.
AB  - Some thio- and the benzoyl-derivatives of deoxamuscarine were synthesized and
      tested as muscarinic agonists using radioligand binding assays and functional
      tests. In comparison with deoxamuscarine, used as reference compound, no
      dimension/distance modification is tolerated for correct lipophilic pocket
      recognition. The substitution of the ammonium group with a sulphonium group
      significantly decreased muscarinic potency. The so-called 'muscarinic sub-site'
      accepts relatively bulky functions as long as it is bound to the cyclopentane
      carrier by an oxygen bridge. Esterification of this moiety increases the M2
      subtype selectivity, while etherification heightens that of M3.

PMID- 9022984
TI  - Quantitative structure-activity relationships of nicotine analogues as neuronal
      nicotinic acetylcholine receptor ligands.
AB  - Quantitative structure-activity relationships of 34 pyrrolidine-modified nicotine
      agonists are investigated for their binding affinity toward neuronal nicotinic
      acetylcholine receptor. The results indicate that a large substituent at the R1,
      R2, and R3 position is detrimental to the binding affinity. Likewise, a large
      substituent at the R2 alpha or R3 alpha position as well as a hydrogen bond
      accepting substituent at the R2 beta position are not beneficial to the binding.

PMID- 9022985
TI  - Nonenzymatic sequence-specific cleavage of duplex DNA via triple-helix formation
      by homopyrimidine phosphorothioate oligonucleotides.
AB  - Phenanthroline was attached covalently to the 5'-terminus of the unmodified and
      modified (3'-terminal phosphorothioate) oligonucleotide sequences,
      TTTTTTCTTCTCTTTCC (OP-17 mer) and TTTTTTTCTTCTCTTTCsC (OPRp-17 mer or OPSp-17
      mer) via a phosphoramidite bond. Simian virus 40 DNA contains a single target
      site for these oligonucleotides. In the presence of copper ions, the efficient
      double-stranded cleavage at 37 degrees C and pH 7.0 was observed by agarose gel
      electrophoresis. The asymmetric distribution of the cleavage sites on the two
      strands revealed that the cleavage reaction took place in the minor groove, even
      though the linker was located in the major groove. Of particular interest are the
      3'-terminal phosphorothioate oligonucleotide-phenanthroline derivatives (Rp or
      Sp), which were found to have cleavage activities of the same order as for the
      oligonucleotide phenanthroline (OP-17 mer). Furthermore, the OPSp-17 mer was
      intact after incubation in 10% fetal bovine serum for 24 h, whereas, the OPRp-17
      mer was slightly more unstable than the OPSp-17 mer. However, the OP-17 mer was
      completely degraded. An increased resistance to nucleases has been observed by
      the introduction of phosphorothioate groups on the 3'-terminus of oligonucleotide
      phenanthroline derivatives. This stabilization should help us to design much more
      efficient chemical recognition enzymes and antisense nucleic acid based anti
      viral therapies, which could be used as tools in cellular biology.

PMID- 9022986
TI  - Chemoprevention of carcinogen-DNA binding: the relative role of different
      oxygenated substituents on 4-methylcoumarins in the inhibition of aflatoxin B1
      DNA binding in vitro.
AB  - Eighteen 4-methylcoumarins bearing methoxy/hydroxy/acetoxy functionalities have
      been reported to effectively inhibit the rat liver microsome-mediated aflatoxin
      B1-DNA binding in vitro. The contribution of functionality on coumarin nucleus
      towards the inhibition of AFB1-DNA binding is in the order acetoxy > hydroxy >
      methoxy. The results illustrate the structure-activity relationship.

PMID- 9023010
TI  - Suppression of insulin receptor activation by overexpression of the protein
      tyrosine phosphatase LAR in hepatoma cells.
AB  - Protein-tyrosine phosphatases (PTPases) play an essential role in the regulation
      of reversible tyrosine phosphorylation of cellular proteins that mediate insulin
      action. In order to explore the potential role of the transmembrane PTPase (LAR)
      in insulin receptor signal transduction, we overexpressed the full-length LAR
      protein in McA-RH7777 rat hepatoma cells and found that modest increases in the
      abundance of LAR protein expression downregulated a number of insulin-stimulated
      cellular responses closely related to the activation of the receptor kinase. An
      increase in LAR protein of 2.4-fold over the level in control cells caused a 40%
      reduction in insulin receptor autophosphorylation in intact cells, without an
      alteration in insulin receptor mass or a change in the insulin-stimulated
      receptor kinase activity measured with partially purified receptors in vitro. In
      addition, insulin-stimulated tyrosine phosphorylation of the endogenous insulin
      receptor substrates IRS-1 and Shc were decreased to 57% and 73% of control,
      respectively, and IRS-1 associated phosphatidylinositol 3'-kinase activity was
      reduced to 47% of control of the cells overexpressing LAR. The present results,
      taken with our recent data demonstrating that reducing the abundance of LAR by
      expression of antisense mRNA enhances insulin receptor signal transduction (Kulas
      D. T., et al. J. Biol. Chem. 270:2435, 1995), supports the hypothesis that LAR
      acts as a physiological modulator of insulin action in insulin-sensitive hepatoma
      cells.

PMID- 9023011
TI  - Involvement of a pertussis-toxin sensitive G protein in the induction of gene
      expression by insulin.
AB  - Binding of insulin to its receptor triggers multiple cellular responses,
      including changes in metabolism and in gene expression, resulting from the
      activation of multiple signalling pathways. Pertussis toxin has been shown to
      block an insulin-stimulated phospholipase C, resulting in an inhibition of the
      synthesis of phospholipid second messengers by insulin. In the present study, we
      investigated the significance of this pathway for the induction of growth-related
      genes by insulin treatment of H35 hepatoma cells. We found that pertussis toxin
      dramatically inhibits the induction of c-fos mRNA by insulin. Although c-jun and
      ornithine decarboxylase induction were also inhibited by pertussis toxin, they
      were much less sensitive than c-fos. These results indicate an important for
      lipid second messengers in mitogenic signalling by insulin and further
      demonstrate distinct roles for this pathway in the induction of c-fos and c-jun.

PMID- 9023012
TI  - Mastoparan causes cell permeabilisation and delayed activation of DNA synthesis
      in Swiss 3T3 fibroblasts.
AB  - Mastoparan, a tetradecapeptide from wasp venom, preferentially activates the
      heterotrimeric G proteins, Go and Gi by promoting GDP/GTP exchange. The peptide
      was originally identified as a potent secretagogue and has since been shown to
      promote DNA synthesis in Swiss 3T3 fibroblasts. Here, we have shown that
      mastoparan (10-20 microM), either alone or in combination with the co-mitogen
      insulin, had no effect on DNA synthesis when incubated with cells for 24 h.
      However, in the presence of insulin, the peptide evoked a small increase in DNA
      synthesis after incubation for 40 h. Thus, unlike other mitogens, mastoparan
      caused a delayed activation of DNA synthesis. At concentrations of mastoparan (15
      17.5 microM) which promoted DNA synthesis, the peptide caused a rapid release of
      lactate dehydrogenase from the cells. These data suggest that the mitogenic
      action of mastoparan occurs by a mechanism distinct from that of physiological
      mitogens.

PMID- 9023013
TI  - Basic fibroblast growth factor-stimulated arachidonic acid release in rat
      pancreatic acini: sequential action of tyrosine kinase, phospholipase C, protein
      kinase C and diacylglycerol lipase.
AB  - This study was performed to evaluate the effect of human recombinant basic
      fibroblast growth factor on arachidonic acid release from rat pancreatic acini
      and to determine the cellular mechanism involved. From enzymatic assays, basic
      fibroblast growth factor did not significantly stimulate phospholipase A2
      activity, whereas it significantly increased diacylglycerol lipase activity.
      Validity of phospholipase A2 or diacylglycerol lipase inhibitors was confirmed by
      their ability to inhibit phospholipase A2 or diacylglycerol lipase activities.
      Basic fibroblast growth factor increased intracellular accumulation and
      extracellular release of arachidonic acid from metabolically labelled acinar
      cells in a concentration- and time-dependent manner. This effect was maximal with
      50 pM basic fibroblast growth factor and became significant after a 5-min
      incubation period. The protein tyrosine kinase inhibitor, 0.5 mM genistein,
      inhibited arachidonic acid release in basic fibroblast growth factor-stimulated
      acini, whereas 100 microM vanadate, a protein tyrosine phosphatase inhibitor,
      enhanced arachidonic acid release. Two phospholipase A2 inhibitors, mepacrine and
      aristolochic acid, failed to attenuate basic fibroblast growth factor-stimulated
      arachidonic acid release. A diacylglycerol lipase inhibitor RHC 80267 at 150
      microM and 50 microM completely inhibited 50 pM basic fibroblast growth factor
      induced intracellular accumulation and extracellular release of arachidonic acid,
      respectively. Furthermore, basic fibroblast growth factor stimulated arachidonic
      acid release was also inhibited by 10 microM U73122 and by 100 nM staurosporine,
      phospholipase C and protein kinase C respective inhibitors. Wortmannin, an
      inhibitor of basic fibroblast growth factor-stimulated phospholipase D, did not
      affect arachidonic acid release. 100 nM 4 beta-phorbol 12-myristate 13-acetate
      also increased arachidonic acid release, an effect also inhibited by
      staurosporine. Taken together, these data demonstrate activation of
      diacylglycerol lipase and arachidonic acid release in pancreatic acini upon
      stimulation by basic fibroblast growth factor, and strongly indicate that
      arachidonic acid release in response to basic fibroblast growth factor depends
      upon the sequential action of tyrosine kinase, phospholipase C, protein kinase C
      and diacylglycerol lipase but not from phospholipase A2 not phospholipase D
      activation.

PMID- 9023014
TI  - A common low-affinity binding site for primary prostanoids on bovine aortic
      endothelial cells.
AB  - [3H]PGE2 and [3H]PGF2 alpha were shown to bind with similar binding capacity and
      dissociation constants to bovine aorta endothelial cells. The similarity in the
      binding parameters suggests that both agonists may bind to the same binding site.
      Displacement of [3H]PGE2 performed with PGE2, PGF2 alpha or U-46619, a
      thromboxane agonist, shows that all three prostanoids displaced the bound
      [3H]PGE2 with comparable potency (IC50 = 10(-7) M). These results indicated that
      the three different prostanoids, which serve as specific agonists to different
      prostanoid receptors, also compete for the same binding site in bovine
      endothelial cells with similar affinity. Comparison of the displacement of
      [3H]PGE2 or [3H]PGF2 alpha by a number of prostaglandin agonists and antagonists
      further supports the notion that the natural prostanoids bind with similar
      affinities to the same binding site. Thus, sulprostone, an EP1/EP3 agonist,
      displaced bound [3H]PGE2 and [3H]PGF2 alpha with IC50 of about 10(-7) M. On the
      other hand, thromboxane antagonists (BAY u-3405 and GR-32191B), EP1 specific
      antagonist (SC-19220) EP1/DP antagonist (AH-6809) and iloprost, a stable
      prostacyclin agonist, failed to displace bound [3H]PGE2 or [3H]PGF2 alpha at a
      concentration range of 10(-9)-10(-6) M. Gradual increase of sodium fluoride
      (NaF), a general activator of G binding proteins, or incubation of permeabilized
      cells with GTP gamma S resulted in a decrease in [3H]PGE2 binding, suggesting
      that the binding site represents a low-affinity common prostanoid receptor which,
      similar to other prostanoid receptors, is probably coupled with G binding
      proteins.

PMID- 9023015
TI  - An inositolphosphate glycan released by TGF-beta mimics the proliferative but not
      the transcriptional effects of the factor and requires functional receptors.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional polypeptide
      that regulates a number of cellular processes including cell growth and
      deposition of extracellular matrix protein. Despite the fact that the signal
      transduction by TGF-beta has been intensively studied, the molecular mechanisms
      of that pathway are not clear. We have studied the possibility that an
      inositolphosphate glycan (IPG) is involved in transmission of the TGF-beta 1
      signal. We show that TGF-beta 1 induces IPG release in both rabbit articular
      chondrocytes (RAC), which are growth stimulated by the factor and Mv1Lu cell
      line, which is growth inhibited. This release requires functional TGF-beta
      heteromeric receptors in these two cell types. We also demonstrate that IPG
      mimics TGF-beta 1-induced growth stimulation in mesenchymal cells (+100%) and
      growth inhibition in epithelial cells (-80%). Moreover TGF-beta receptor I (T
      beta R-I) is not required for inhibition of proliferation induced by IPG since
      derivated mutants of the Mv1Lu cell line lacking T beta R-I intracellular domain
      (R-1B) are significantly inhibited (-65%). Additionally, we show that IPG does
      not take part in the signalling pathway that leads to activation of matrix gene
      transcription. These results suggest that TGF-beta effects on growth regulation
      and extracellular matrix synthesis implicate two different signalling pathways,
      IPG being only involved in growth regulation.

PMID- 9023016
TI  - Activation of a cyclic nucleotide phosphodiesterase 4 (PDE4) from rat thymocytes
      by phosphatidic acid.
AB  - The cytosolic cyclic nucleotide phosphodiesterase (PDE) activity from rat
      thymocytes was resolved into five peaks by HPLC. Only two forms of the cAMP
      specific PDE4 were found to be sensitive to physiologically relevant phosphatidic
      acid (PA) concentrations. PA activated the PDE4-peak 3 form, the fatty acid
      composition and unsaturation degree determining the efficiency of PA. The PDE4
      peak 2 form was inhibited only by PA with saturated fatty acyl groups. PDE4
      activation was specific of anionic phospholipids, a free phosphate group in the
      phospholipid molecule being required for maximum activation. These results
      suggest that PA may contribute to the lowering of cAMP level required in the
      early steps of a lympho-proliferative response, thus regulating immune functions
      through PDE4 activation.

PMID- 9023017
TI  - Regulation of motility of cells from marine sponges by calcium ions.
AB  - Sponges are known not to contain muscle and nerve cells. Since sponge cells are
      characterized by high motility we determined the effect of intracellular calcium
      ion concentration ([Ca2+]i) on their motility. Addition of the Ca2+ ionophore
      ionomycin to dissociated cells from the marine sponge Suberites domuncula caused
      in Ca(2+)-containing artificial seawater (ASW) an increase in motility from 0.2
      micron/min (absence of the ionophore) to 3.7 microns/min (presence of ionomycin).
      When the experiments were performed in Ca(2+)-free medium, no effect of ionomycin
      could be observed. In parallel experiments the changes of [Ca2+]i using the dye
      Fura-2 were measured. The experiments revealed that ionomycin causes an influx of
      Ca2+ into the cytosol of cells suspended in Ca(2+)-containing artificial
      seawater. In contrast, if cells were suspended in Ca(2+)-free artificial
      seawater, no increase of [Ca2+]i occurred. Incubation of cells in the presence of
      inhibitors, specific for endoplasmatic Ca(2+)-ATPase in mammals such as
      thapsigargin, cyclopiazonic acid, or 2,5 di-t-butylhydrochinone, did not
      influence the [Ca2+]i if cells were suspended in Ca(2+)-free artificial seawater.
      From these data we conclude that the [Ca2+]i is primarily regulated through
      channels in the plasma membrane. In addition we summarize experimental evidence
      indicating that the [Ca2+]i is involved in the control of cell motility. From the
      marine sponge Geodia cydonium a partial sequence of the myosin cDNA has been
      cloned. The deduced amino acid sequence comprises highest homology to nonmuscle
      myosin type II found in higher invertebrates and vertebrates. Taken together,
      these data show that the [Ca2+]i level in sponge cells can be modulated by
      incubation with ionomycin. An increase of the Ca2+ level parallels with higher
      motility of cells, suggesting an activation of Ca(2+)-dependent protein kinases
      of myosin type II. Investigations on the ionomycin-activated influx of Ca2+ into
      the cytosol revealed that predominantly the Ca2+ channels in plasma membrane
      control the level of [Ca2+]i.

PMID- 9023018
TI  - Sexually abused children in a national survey of parents: methodological issues.
AB  - In a national survey of 1,000 parents, which primarily concerned disciplinary
      practices and violence toward their children, two questions were asked about
      whether the children had been sexually abused. This was to assess the feasibility
      of epidemiological research on contemporaneous sexual abuse using parental
      interviews rather than the usual adult retrospective approach. From these
      questions, rates of sexual abuse for children currently 0-17 were estimated at
      1.9% in the last year and 5.7% ever. The cases making up these rates included a
      nearly equal number of boys and girls and no female victims between the ages of 9
      and 12, a distribution different from those generally obtained by other
      epidemiological methods, but due possibly in this case to normal sampling
      variation. Cases were more likely to be disclosed for children whose parents had
      themselves been sexually abused, who were from lower income households, or who
      were living with only one biologic parent. Although some of the findings suggest
      caution in generalizing about child sexual abuse from survey samples of parents,
      the method is worthy of exploration if only to gain better epidemiologic data
      about parent knowledge, reaction, reporting, and coping strategies.

PMID- 9023019
TI  - Encopresis and sexual abuse in a sample of boys in residential treatment.

PMID- 9023020
TI  - Crocodile talk: attributions of incestuously abused and nonabused sisters.
AB  - This study is a qualitative analysis of the attributions of sisters (abused and
      nonabused sister dyads, n = 10 and abused sister dyads, n = 10) who grew up in an
      incestuous family. While the sibling subsystem is reported to be the most
      important and enduring relational environment in the life of the family, little
      is known about the cognitions and attributions of siblings, regarding incest.
      This study examines the attributions of participants regarding the general
      sibling group, victim selection and nonselection, as well as attributions
      regarding jealousy, protection, and guilt within the sister relationship.

PMID- 9023021
TI  - Factors affecting utilization of treatment services by sexually abused girls.
AB  - This study describes the naturalistic therapy experiences of a sample of sexually
      abused girls and the relationship of these experiences to demographic factors,
      abuse experiences, psychopathology, and family functioning. The sample consisted
      of 81 sexually abused girls, aged 6 to 16, participating in a longitudinal study
      of the effects of sexual abuse. Results indicated strong effects for abuse
      experiences and child psychopathology on the total amount of therapy received.
      Patterns of treatment utilization were associated with ethnic minority status,
      but these differences are confounded by differing abuse experiences for racial
      groups in the sample. Other patterns of treatment utilization are discussed, as
      well as issues for further research and implications for treatment providers.

PMID- 9023022
TI  - A study of potential risk factors for sexual abuse in childhood.
AB  - Research aimed at identifying risk factors for childhood sexual abuse (CSA) is
      crucial for the development of preventative strategies. This study examined the
      relationship between a number of possible risk factors and CSA in a community
      sample of women using multivariate analysis and carefully operationalized
      variables. The variables significantly associated with CSA were physical abuse,
      having a mother who was mentally ill, not having someone to confide in, and being
      socially isolated. With the exception of physical abuse, different predictors
      emerged for abuse before and after age 12. Social isolation and experiencing the
      death of a mother were significant predictors for abuse before age 12, while the
      predictors of CSA after age 12 were physical abuse and a mentally ill mother. For
      abuse perpetrated by a family member, the significant predictors of CSA were
      physical abuse, having no one to confide in, having no caring female adult, and
      having an alcoholic father. For girls abused by someone outside of the family,
      the significant predictors were physical abuse, social isolation, mother's death,
      and having an alcoholic mother. While CSA can happen to any child, this study
      highlights circumstances that may increase the chances of abuse and should form
      the basis of prevention and intervention strategies.

PMID- 9023023
TI  - Reports of severe physical punishment and exposure to animal cruelty by inmates
      convicted of felonies and by university students.
AB  - A self-report questionnaire designed to assess abusive childhood environments and
      exposure to animal cruelty was administered to 314 inmates in a prisoner
      classification center. Although high rates of physical punishment characterized
      the entire sample, persons charged with violent, but nonhomicidal crimes reported
      more severely punitive childhood histories than those charged with homicidal
      crimes, sex offenses, and nonviolent offenses. Some exposure to animal cruelty
      was widespread in the sample, but there was no association between experiencing
      animal cruelty and the type of crime committed. Moreover, there were only modest
      associations between animal cruelty experiences and the aversive childhood
      histories of the subjects, as well as the subjects' reported use of physical and
      sexual coercion in dating and intimate relationships. To determine whether the
      high base rate of exposure to animal cruelty was unique to the incarcerated
      sample, a follow-up study was completed with university undergraduates.
      Widespread exposure to some animal cruelty was reported by undergraduates; there
      were modest associations between reporting animal cruelty and reporting punitive
      and acrimonious childhood histories. In general, the findings were consistent
      with the hypothesis that there is an association between punitive childhood
      histories and antisocial behavior but not consistent with the hypothesis that
      exposure to animal cruelty is importantly related to antisocial behavior or child
      maltreatment.

PMID- 9023024
TI  - Maltreatment, conscience functioning and dopamine beta hydroxylase in emotionally
      disturbed boys.
AB  - OBJECTIVE: Identify associations among early maltreatment, sufficiencies, and
      psychopathological interferences in the domains of conscience functioning and low
      serum dopamine beta hydroxylase activity. METHOD: Nineteen emotionally disturbed
      boys screened for maltreatment experiences were compared according to age at
      onset of maltreatment, enzyme activity, and their conscience functioning in the
      domain of moral valuation. They were also compared in conscience functions to 19
      age and sex matched normal counterparts. RESULTS: Subjects who endured
      maltreatment prior to 36 months had developmental delays and interferences with
      functioning in more conscience domains than those who were either spared such
      experiences or who endured maltreatment later in life. Subjects with low enzyme
      activity had significantly more interference with authority and peer valuation
      than subjects with high enzyme activity. Greater interference with valuation was
      associated with lower enzyme activity and more frequent abuse prior to 36 months.
      CONCLUSIONS: Psychosocial sequelae of early maltreatment have been identified in
      the domains of conscience. An association has been established between
      pathological interference in the domain of moral valuation and a putative
      neurobiologic sequelae of early maltreatment. Implications for future research in
      the psychobiology of maltreatment are discussed.

PMID- 9023025
TI  - Child-care personnel's failure to report child maltreatment: some Swedish
      evidence.
AB  - Professionals who are legally required to report suspicions of child abuse and
      neglect to child protective agencies have often been found not to do so. In this
      article, 341 child-care institutions in three suburbs of Stockholm were surveyed
      for suspected child abuse. Of the 3,737 children attending these child-care
      institutions, 3% (N = 112) were suspected of being maltreated. Of these suspected
      cases, only 37% were reported to the Child Protective Agencies (CPA).
      Furthermore, interviews with the directors of the nursery schools revealed that
      there was a considerable delay in reporting suspicions of child abuse to the CPA.
      A follow-up study conducted approximately 5 years after the suspicions were first
      identified showed that 43% of the suspected children were still unknown to the
      CPA. Data also indicates that one possible reason for the low degree of reporting
      is the way in which the reports have been processed by the CPA.

PMID- 9023026
TI  - Discriminant validity of the TSC-40 in an outpatient setting.
AB  - This study examines the discriminant validity of the Trauma Symptom Checklist
      (TSC-40) in a clinical sample. The TSC-40 was developed as a research instrument
      for assessing the impact of a history of sexual victimization. Previous validity
      studies used nonclinical samples of women (Elliott & Briere, 1992; Gold, Milan,
      Myall, & Johnson, 1994). In the present study, the TSC-40 was administered to 103
      men and 79 women requesting services at two outpatient clinics. Information about
      sexual victimization was collected from the client during intake and from the
      therapist after the client had received 6 months of therapy. A history of CSA was
      associated both with high symptom levels across symptom dimensions, and,
      specifically, with elevation on the trauma subscale of the TSC-40. The findings
      support the view that, in a clinical setting, CSA is associated both with
      generalized distress and with PTSD symptoms.

PMID- 9023027
TI  - Organization of child disability services.

PMID- 9023028
TI  - Early intervention for young children with developmental delay: the Portage
      approach.
AB  - It is now 20 years since the Portage Home Teaching model of early intervention
      was introduced into the UK. In this paper, an overview of the Portage Model and
      rationale is provided, achievements over the past two decades are noted and
      related research and evaluation studies are reviewed. A number of areas for
      future development are also highlighted. These include: issues of quality
      control; the multi-cultural dimension of Portage; multi-agency collaboration;
      professional training needs of Portage personnel; and influencing central
      government policy relating to families who have a young child with special needs.

PMID- 9023029
TI  - Beyond child development centres: care coordination for children with
      disabilities.
AB  - A specific model of care coordination for children with disabilities is
      described, comprising parental empowerment, a defined client population,
      individual tailoring of service based on assessment of need, inter-agency
      collaboration beyond existing team boundaries, continuity of named professional
      contact across transitions important to families, and a named care coordinator.
      The first stages of local implementation of the model are described for children
      with a disability making the transition into nursery school provision.
      Qualitative findings from interviews with families and care coordinators are
      presented, and the possibility of care coordinators providing a Named Person
      function is examined.

PMID- 9023030
TI  - Improving services to Asian families and children with disabilities.
AB  - There is a clear need to improve the delivery of services to Asian families and
      their children with disabilities. This paper describes some of the key points
      where communication and access may break down. It offers principles to guide
      assessments of children, and makes recommendations on ways of working with
      interpreters, monitoring uptake of services and strategies for supporting and
      informing Asian families.

PMID- 9023031
TI  - Evaluating family-centred service using a measure of parents' perceptions.
AB  - This article describes the use of a newly-developed measure of parents'
      perceptions of health care providers' behaviours (Measure of Processes of Care
      MPOC) to evaluate the family centredness of children's rehabilitation services.
      The measure was developed with the participation of more than 1600 parents of
      children with chronic neurodevelopmental conditions throughout Ontario. It
      assesses five domains: enabling and partnership; providing general information;
      providing specific information about the child; coordinated and comprehensive
      care; and respectful and supportive care. By comparing the perceptions of parents
      receiving services from three different types of organizations or programmes, we
      demonstrated that the MPOC can pick up differences between parents in their
      experiences of caregiving. We also demonstrated that the MPOC is able to detect
      differences in how parents view the family-centredness of services provided by
      individual centres. The data indicate that the MPOC has appreciable utility in
      providing programmes and services with a description of their current level of
      family-centred service as perceived by parents. The strengths, limitations and
      potential uses of the measure in other contexts are discussed.

PMID- 9023033
TI  - Issues in multidisciplinary teamwork for children with disabilities.
AB  - This paper presents a review of key issues surrounding multidisciplinary work in
      relation to the care of children with disabilities and their families. The
      discussion is based on experience of working in a child development team and
      research visits to teams around Britain at the beginning of the 1990s. An
      outstanding feature of child disability services is their organizational
      diversity. The research found that district interagency planning groups were a
      rarity, as were multiagency management groups for teams. Thus it was rare for
      teams to have clear lines of external accountability. Similarly leadership and
      management structures within the teams had a profound influence on their
      effectiveness. Issues are highlighted for identifying good practice and for
      further development of services.

PMID- 9023032
TI  - The relationship between audit, research and policy: lessons from a community
      paediatric audiology service.
AB  - The pace of medical change is in danger of paralysing the process of decision
      making, particularly in services where clinical improvements occur more slowly
      than the introduction of new interventions. Audit within an individual district
      enables staff to monitor progress towards desired goals and standards but rarely
      generates sufficient data to inform decision making about major policy changes.
      The paper describes how the findings from nine audits of a community paediatric
      audiology service over a 13-year period were combined with reviews of the
      literature, resulting in a series of changes to a children's audiological
      service. The interest and commitment of all the staff involved were maintained by
      involving them in the process and using them as a valuable source of qualitative
      data. Audit must be thorough and should be based on precise case definition and
      comprehensive casefinding if the results are to be meaningful. It is a more
      powerful means of achieving improvements in systems if it is combined with
      research evidence, and a readiness to change the system if the agreed goals are
      not being attained.

PMID- 9023034
TI  - Child development teams: are they fulfilling their purpose?
AB  - Child development teams (CDTs) have been in existence for a quarter of a century,
      yet little is known of how they function or what they do. This paper originated
      in a national seminar on how CDTs function and what they seek to achieve. It
      discusses the wide range of practice in CDTs across Britain and the apparent
      deficiencies in service provision for certain types of disability. Since each
      child has a unique set of needs, the composition of the team must be flexible and
      responsive to the changing circumstances of each child. The need for a
      philosophical shift to take account of changing parental expectations is
      stressed. There is a need for further research on a number of topics, including:
      the patterns of service provision and the differences between districts; the
      implementation of what is already known about standards of good practice; the
      possible role of a charter for disabled children and their families; the training
      needs of future CDT professionals.

PMID- 9023035
TI  - Acceptability of bio-engineered vaccines.
AB  - For hundreds of years bacterial and viral vaccines have been-in a way
      bioengineered and were generally well received by the public, the authorities,
      and the medical profession. Today, additional tools, e.g. molecular biology,
      enable new approaches to the development of better and safer products. Various
      vaccines derived from gene technology have now been licensed for commercial use
      and are acknowledged within the scientific community. Acceptance by the public
      and the politicians is, however, negatively influenced by the discussions
      encompassing gene manipulation in man and animals, transgenic plant, and "novel
      food". Lack of information leads to confusion and fear. Concurrently, the absence
      of spectacular and life-threatening epidemics limits the perceived value of
      immune prophylaxis and its benefits. Scientists in institutes and industry are in
      a position to stimulate acceptability of bio-engineered vaccines by following
      some simple rule: (1) adherence to the principles of safety; (2) establishment of
      analytical and control methods; (3) well functioning regulatory and reporting
      systems; (4) demonstration of usefulness and economic benefits; (5) open
      communication; and (6) correct and prudent wording.

PMID- 9023036
TI  - Adjuvanticity of pGPL-Mc and LRS in the immune responses of monkeys to oral
      immunization with diphtheria and tetanus toxoids.
AB  - Experiments were carried out to examine the adjuvanticity of polar
      glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) or the London rocket seed
      (LRS) when combined with diphtheria and tetanus toxoids in an oral immunization
      of the African green monkey. The results showed that none of the monkeys
      receiving diphtheria and tetanus toxoids combined with 25 mg/kg of pGPL-Mc showed
      an increase in the the level of diphtheria antitoxin (DA) on the third and sixth
      weeks following the first and the second immunizations. One monkey from this
      group responded with increased seroneutralizing antibodies 3 weeks after the
      third feeding. On the other hand, one monkey, 3 weeks after the first
      immunization, and three monkeys, 3 weeks after the second and third oral
      vaccinations, showed an increase in specific anti-diphtheria antibody responses
      when the toxoids were combined with 25 mg/kg of LRS. The anti-diphtheria
      antitoxin responses of monkeys receiving diphtheria and tetanus toxoids combined
      with 50 mg/kg of pGPL-Mc or 50 mg/kg of LRS were significantly enhanced compared
      to the groups administered 25 mg/kg of the two adjuvants. The increase was
      observed in four out of five pGPL-Mc administered and in three out of five LRS
      receiving monkeys. The results show that pGPL-Mc induced the highest titres of
      anti-diphtheria antitoxin compared to LRS, whereas the level of anti-diphtheria
      antitoxin titre of the two monkeys receiving the toxoids alone was less than 0.1
      i.u./ml of serum throughout the experiment. According to the statistical
      analyses, no significant differences were recorded between the diphtheria
      antitoxin responses of monkeys following the first, second or third
      administration of LRS-adjuvated diphtheria and tetanus toxoids. However, a
      significant difference (P < or = 0.05) was observed in the diphtheria antitoxin
      response between the first and the second immunization of monkeys administered
      with toxoids adjuvated with 50 mg/kg of pGPL-Mc. The tetanus antitoxin responses
      of all monkeys were less than 0.1 i.u. of antitoxin per millilitre of serum
      throughout the study, which is considered not to be protective. However, we have
      recorded an anti-tetanus antitoxin titre of more than 0.2 i.u./ml of serum in one
      monkey that received diphtheria and tetanus toxoids combined with 50 mg/kg of
      pGPL-Mc.

PMID- 9023037
TI  - Effect of serum from breast- or formula-fed infants on polymorphonuclear
      leukocyte function.
AB  - The aim of the present study was to determine the influence of serum from formula
      and breast-fed infants on neutrophil function (as measured by the attachment and
      phagocytosis of Candida albicans) as well as the chemoattractant activity of the
      serum. The results indicate that: (a) serum from breast-fed infants induces a
      greater chemoattractant activity in neutrophils than serum from 3-month-old
      formula-fed infants; (b) the highest values of the attachment capacity were
      obtained after incubation of neutrophils with serum from 1-month-old breast-fed
      infants; and (c) serum from breast-fed infants induces a greater phagocytic
      capacity against C. albicans in neutrophils than serum from formula-fed infants.

PMID- 9023038
TI  - Phenotype and serotype of Pasteurella multocida isolates from diseases of dogs
      and cats in Zimbabwe.
AB  - A variety of disease manifestations, comprising skin bite wounds, pyothorax,
      respiratory and genitourinary tract infections, in 202 dogs and cats presented to
      the University Clinic, were investigated for the presence of Pasteurella
      multocida. Of these, 25-42% of various cases (69) were found to be infected with
      P. multocida. P. multocida-associated respiratory tract infections were more
      common than bite wounds or genitourinary tract infections. The regimen of
      treatment consisted of those antibiotics, sensitivity to which had been confirmed
      in vitro. Following detailed characterization of the isolates of P. multocida, in
      order to assign them to the reclassified taxa of Pasteurella, a preponderance of
      P. multocida subspecies multocida and septica were recorded. There did not appear
      to be a correlation between the reclassified taxa and their serotypes. Certain
      strains of different species or subspecies belonged to a common serotype and vice
      versa. However, the strains which were serotyped belonged to capsular type A,
      except for a solitary isolate from a cat which was capsular type D. Type D is
      known to cause atrophic rhinitis and does not appear to have been isolated either
      from a dog or a cat. Two strains, one from a dog and another from a cat, were
      identified as group EF-4 bacteria. This group of organisms has been incriminated
      in human wounds resulting from dog/cat bites, and has so far not been reported in
      Africa. Three different species, P. stomatis, P. dagmatis and P. multocida
      subspecies multocida were simultaneously isolated from a case of chronic
      bronchitis in a dog. There was no evidence of any relationship between disease
      manifestation in a host and the isolation of a particular taxon of Pasteurella,
      except that P. canis and Pasteurella taxon 16 were only isolated from dogs.

PMID- 9023039
TI  - Bacterial strains isolated from eggs and their resistance to currently used
      antibiotics: is there a health hazard for consumers?
AB  - In order to study the putative transfer of antibiotic resistance from poultry to
      humans, hens' eggs were examined for the presence of various pathogens.
      Staphylococcus, Enterobacter, Escherichia, Proteus and Pseudomonas spp. were the
      most frequently isolated genera. Sensitivity tests, performed with the Kirby
      Bauer technique, showed the presence of resistant strains of Staphylococcus
      aureus (to penicillin-G, tetracycline, erythromycin, clindamycin, cefalosporins,
      oxacillin, gentamycin, chloramphenicol and tobramycin), Enterococcus faecalis (to
      ampicillin, ciprofloxacin, clindamycin, gentamycin and tetracyclin), Escherichia
      coli (to tetracycline, erythromycin, ampicillin and cefalosporins), Enterobacter
      cloacae (to ampicillin, amoxycillin plus clavunalic acid, erythromycin and
      tetracycline), Pseudomonas stutzeri (to erythromycin and chlorampenicol) and
      Citrobacter freundii (to ampicillin, amoxycillin plus clavunalic acid,
      cefalosporins and co-trimoxazole).

PMID- 9023040
TI  - Experimental and natural infection with Bartonella henselae in domestic cats.
AB  - Domestic cats were experimentally infected with culture propagated Bartonella
      henselae by intradermal (i.d.) and intravenous (i.v.) routes. Cats were more
      efficiently infected by the i.d. (8/8 cats) than by the i.v. (2/16) route.
      Bacteremia was detected 1-3 weeks following inoculation and lasted for most cats
      for 1-8 months. However, one naturally infected cat was observed for 24 months
      and was found to be cyclically bacteremic, with bacterial levels varying one
      hundred fold or more from one period to another. No clinical or hematologic
      abnormalities were observed in any of the infected cats, even at the peak of
      bacteremia. Two cats that had become abacteremic were resistant to reinfection
      when inoculated with B. henselae a second time. Horizontal transmission through
      intimate contact between bacteremic and susceptible cats did not occur, and
      antibody positive bacteremic queens did not transmit the infection to their
      kittens in utero, peri-partum or post-partum. Only four of the 18 kittens
      acquired detectable levels of maternal antibody following nursing, which
      disappeared by 6 weeks of age. These studies indicate that B. henselae exists in
      an almost perfect host-parasite relationship with its feline host, but that most
      cats can ultimately rid themselves of the infection. The susceptibility of cats
      to intradermal infection and the lack of direct cat-cat transmission are
      compatible with possible arthropod vectors.

PMID- 9023041
TI  - Structural polypeptides of different clinical strains of avian adenovirus type-1.
AB  - The polypeptides of two liver strains, two ovarian strains and one standard
      strain of avian adenovirus-1 (AAV-1) were analysed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE), Western blot using polyclonal
      antibodies to all the strains and isoelectric focusing (IEF). All the strains had
      11 polypeptides and molecular weight varied between 9 and 100 kDa. The
      polypeptide pattern was similar in all the strains as revealed by SDS-PAGE and
      Western blot. However, some differences among the strains on the basis of
      isoelectric point of polypeptide were observed by IEF.

PMID- 9023042
TI  - Humoral immune response of chicks to different clinical isolates of avian
      adenovirus type-1.
AB  - The humoral immune response of 7-day-old chicks to different strains of avian
      adenovirus (AAV) type-1 was determined by counter immunoelectrophoresis (CIE) and
      enzyme-linked immunosorbent assay (ELISA). In CIE antibody was detected 14 days
      post-infection (PI) whereas in ELISA antibody was detected 7 days PI. The ELISA
      titre reached its peak at 21 days PI in all groups. The pattern of immune
      response among the groups was found to be similar.

PMID- 9023044
TI  - Echinococcosis.
AB  - Hydatids, the intermediate stages, or metacestodes, of the tapeworm genus,
      Echinococcus, present a major immunological problem; they survive, grow and
      metastasize in immunized hosts which are protected against reinfection and
      possess effector mechanisms capable of killing the parasite. Explanations for
      this state of concomitant immunity have been made from investigations of
      avoidance strategies, genetics and quantitative hydatid growth. The latter study
      suggests that the host-parasite relationship is sustained as a dynamic
      equilibrium between parasite growth and acquired immunity, the balance being
      subject to mutual regulation and including the possibility of spontaneous
      rejection of the parasite. Two immunoregulatory, or cytokine-like, factors have
      been detected in hydatids of Echinococcus spp. One appears to be a mediator of
      the previously reported mitogenic effects of hydatids. Recent evidence has linked
      these effects to generation of T-suppressor populations. The second factor
      interferes with the interaction of macrophages and T-cells, mimics the effect of
      metacestode infection in impairing the accessory action of macrophages in
      lymphoproliferative responses, and is suppressive for rosette-forming cell
      responses against third-party antigens. It is suggested that these factors form
      part of a primary homeostatic mechanism regulating hydatid growth and immunity.

PMID- 9023043
TI  - Evaluation of protective efficacy of an Actinobacillus pleuropneumoniae serotype
      1 lipopolysaccharide-protein conjugate in mice.
AB  - Actinobacillus pleuropneumoniae is the causative agent of porcine
      pleuropneumonia. The major adhesin of A. pleuropneumoniae has previously been
      identified as a lipopolysaccharide (LPS), and more recently, we demonstrated that
      high molecular mass LPS were involved in A. pleuropneumoniae adherence to porcine
      respiratory tract cells. We postulated that immunization with a LPS-based vaccine
      may confer a protective immunity. The high molecular mass O-polysaccharides
      obtained after acid hydrolysis and chromatographic separation were conjugated to
      bovine serum albumin (BSA) as a protein carrier. Groups of mice were injected
      twice with the following antigen preparations: whole-cell preparation, outer
      membrane preparation, O-polysaccharide-BSA conjugate, hydrolyzed LPS and
      phenol/water extracted LPS. A combination of different adjuvants was also used
      during these immunization procedures to induce a stronger immunological response
      to the polysaccharide antigen. Two weeks after the second injection, the mice
      were challenged intranasally with either homologous A. pleuropneumoniae serotype
      1 strain or a serotype 5 strain. The highest survival rate, up to 80%, compared
      to the control groups (P < 0.05), was recorded when the mice were injected twice
      with 15 micrograms of carbohydrates of O-polysaccharide-BSA conjugate mixed with
      the saponin-derived adjuvant Quil A. Survival rates of between 60 and 70%, twice
      those observed in the control groups immunized with PBS, were recorded in mice
      injected with the O-polysaccharide-BSA conjugate mixed with other adjuvant
      preparations such as alhydrogel, peanut oil and Freund's incomplete adjuvant.
      However, the protection induced by the conjugate antigen preparation was serotype
      specific, because mice challenged with a serotype 5 strain were killed. Taken
      together, these results confirm the important role of A. pleuropneumoniae LPS in
      pathogenesis.

PMID- 9023045
TI  - Biochemical characterization of FMDV A10 and A22 subtypes by PAGE and IEF.
AB  - Both polyacrylamide gel electrophoresis (PAGE) and iso-electric focusing (IEF)
      have been standardized using the sucrose density gradient purified 146S particles
      of FMD virus subtypes A10 and A22. Differences in the molecular weights of
      structural proteins (VP1, VP2 and VP3 of two subtypes (A10 and A22) of FMDV have
      been revealed in PAGE but no appreciable differences in the pI of VP1, VP2 and
      VP3 is found in IEF.

PMID- 9023046
TI  - Integrin expression on cell adhesion function and up-regulation of P125FAK and
      paxillin in metastatic renal carcinoma cells.
AB  - Integrins from normal human renal cortex epithelial cells (RCEC) and from four
      renal carcinoma lines (metastatic Caki-1, non-metastatic Caki-2, metastatic ACHN,
      and non-metastatic 769-P) were compared by immunoprecipitation with specific anti
      integrin antibodies. Integrin alpha 2 was present in normal RCEC, but absent in
      all four tumor lines. There was a 2.0-3.0 fold decrease of alpha 3 and beta 1 in
      localized tumor lines, and a further 5.0-7.0 fold decrease in metastatic lines
      over their expression in normal renal cells. No alpha V was detected in Caki-1
      cells. The greatest adhesion of all cells occurred in the presence of a
      stimulatory anti-alpha 3 antibody, mediated by specific matrix proteins employed
      as substrates, while anti-beta 1 treatment dramatically inhibited cell attachment
      on collagen IV, plasma fibronectin, laminin and merosin substrates. In addition,
      the mRNA expression of focal adhesion kinase (p125FAK) and paxillin were up
      regulated (2.0-2.5 fold increase) in the metastatic Caki-1 cells over normal
      RCEC. The alteration of integrin subunits alpha 2, alpha 3, alpha V, beta 1, as
      well as p125FAK and paxillin may contribute to the pathogenicity and/or
      metastatic propensity of renal epithelial tumors. The up-regulation of paxillin
      independently or in concert with p125FAK as shown in this study indicates its
      significant role as a potential marker of metastasis in renal carcinoma cells.

PMID- 9023047
TI  - Partial characterization of ovine skeletal muscle proteoglycans and collagen.
AB  - Ovine longissimus dorsi and biceps femoris muscles were analyzed for proteoglycan
      content, collagen and lysine aldehyde-derived collagen crosslinking
      concentrations at 2-4 days, six-month-old, and six-year-old stages of
      development. Tissue extracted proteoglycan molecular sieve distribution on a
      Sephacryl S-200HR column revealed two proteoglycan populations with estimated
      relative molecular weight ranges of 200,000 to 250,000 daltons and 23,000 to
      70,000 daltons. The molecular sieve distribution was similar between the two
      muscles within a developmental age, but changed as a function of developmental
      age. Primary culture from both the longissimus dorsi and biceps femoris muscle
      liberated proteoglycans into the culture medium. In contrast to the tissue
      extracted proteoglycans, at the six-year-old stage of development, culture medium
      liberated proteoglycan Sephacryl S-200HR molecular sieve distribution differed
      between the two muscles. In both the tissue extracted and medium liberated
      proteoglycans at all developmental stages, nitrous acid deamination demonstrated
      the presence of heparan sulfate. Immunoblot analysis of the tissue extracted
      proteoglycans indicated the presence of decorin at each developmental stage.
      Longissimus dorsi and biceps femoris collagen concentrations (5.13 +/- 0.9 vs.
      5.53 +/- 1.5%, respectively) and crosslink concentrations (0.07 +/- 0.01 moles
      HP/mole collagen) were initially similar between the two muscles; however, by six
      months the muscles differed in both collagen concentration (1.72 +/- 0.5 and 2.53
      +/- 0.7%, respectively) and crosslinking (0.24 +/- 0.02 and 0.27 +/- 0.03 moles
      HP/mole collagen, respectively). At six years of age, both the longissimus dorsi
      and biceps femoris exhibited slightly elevated collagen concentrations (2.49 and
      3.05%, respectively) while crosslinking values were decreased relative to values
      at six-months of age (0.11 +/- 0.01 and 0.18 +/- 0.01 moles HP/mole of collagen,
      respectively). The results from this study indicate that skeletal muscle
      proteoglycans and collagen show developmental changes, which suggests that they
      are subject to developmental regulation.

PMID- 9023048
TI  - Biochemistry of periodontal connective tissues and their regeneration: a current
      perspective.

PMID- 9023049
TI  - Polarized FT-IR microscopy of calcified turkey leg tendon.
AB  - Polarized Fourier transform infrared microscopy (FT-IRM) was used to assess the
      orientation of mineral and matrix components of the normally calcified turkey leg
      tendon. Two groups of tendon, < 16 weeks of age (young) and > 60 weeks of age
      (old), were analyzed. Linear sequences from calcified, non-calcified, and
      transitional regions of the tendons were examined. Spectra collected in the
      "parallel polarization" mode were acquired with the electric vector of the
      infrared radiation parallel to the collagen fiber axis whereas spectra collected
      in the "perpendicular polarization" mode were acquired with the electric vector
      of the infrared radiation perpendicular to this axis. The v2 carbonate (850-890
      cm-1) and v1, v3 phosphate (900-1180 cm-1) contours of the tendon mineral as well
      as the collagen amide I, II, and III bands of the extracellular matrix all
      displayed marked dichroism. The CO3(2-) ions substituted for PO4(3-) (878 cm-1,
      type B substitution) in the tendon mineral displayed parallel dichroism while the
      CO3(2-) ions substituted for OH (871 cm-1, type A substitution) in the tendon
      mineral displayed perpendicular dichroism. These orientational effects for both
      sites of carbonate substitution were greater in the older animals. The
      polarization properties of the v1, v3 phosphate contour were analyzed by use of
      an empirical anisotropy parameter (A), the value of which monitors the degree of
      orientation. This index significantly increased in the older animals indicating
      that aging produces a more highly oriented mineral. The amide I, II, and III
      contours of the collagen extracellular matrix also exhibited marked dichroism.
      The amide I component exhibits perpendicular dichroism while the amide II and III
      components exhibit parallel dichroism. The current study demonstrates the ability
      of polarized FT-IRM to assess the orientation of the mineral and matrix
      components of calcified tissue at the microscopic level.

PMID- 9023050
TI  - Collagen and proteoglycan production by bovine fetal and adult chondrocytes under
      low levels of calcium and zinc ions.
AB  - The experiments described herein tested the effects of CaCl2 and ZnCl2, added at
      various concentrations in the culture medium, upon the synthesis of collagen and
      proteoglycan by adult and fetal (articular, epiphyseal and hypertrophic) bovine
      chondrocytes maintained in high density multilayer cultures. CaCl2 concentrations
      below 0.5 mM or the addition of 1-50 microM ZnCl2 to the medium selectively
      promoted the production of collagen by all four populations of chondrocytes but
      had no effect on fibroblasts. Further, these changes had no statistically
      significant effect on the incorporation of 35S-sulfate into macromolecules or on
      the synthesis of gelatinase A, measured by gelatin zymography. The addition of
      CaCl2 and ZnCl2 at these concentrations did not result in a change in the
      relative proportion of non-crosslinked 3H-collagen molecules (synthesized in the
      presence of beta-aminopropionitrile) partitioning in the cell layer and medium
      compartments, and did not appreciably alter the pattern of collagens synthesized
      by any of the cell populations. The hypertrophic cells synthesized high levels of
      collagen type X in the presence as well as absence of exogenously added cations.
      However, CaCl2 at 10 mM caused a marked upregulation of collagen type X synthesis
      by a preparation of chondrocytes derived from the entire growth plate, consistent
      with the view that calcium at that concentration stimulated the differentiation
      of some of the cells into hypertrophic chondrocytes.

PMID- 9023051
TI  - The effect of compressive loading on proteoglycan turnover in cultured fetal
      tendon.
AB  - A fibrocartilaginous tissue develops in tendon at the point where the tendon
      wraps under bone and is subjected to transverse compressive loading in addition
      to tension. This tissue is characterized by a high level of large proteoglycan
      (aggrecan), which could accumulate because of increased synthesis, diminished
      turnover, or both. To examine the effect of loading on proteoglycan turnover
      segments of fetal tendon in sterile culture were subjected to cyclic, uniaxial
      compression loading to 30% of initial thickness once every 6 sec. for 72 h, and
      then allowed to incorporate 35S-sulfate for 12 h. The rate of loss of newly
      synthesized 35S-proteoglycans from tissue was determined during subsequent
      culture for up to 12 days, with or without continued loading. Proteoglycan was
      lost from fetal tendon segments rapidly during the first 3 days of culture and
      slowly thereafter. Loss of newly-synthesized proteoglycan from adult tendon
      fibrocartilage was linear, with a half life of 12 d. Segments of fetal tendon
      subjected to cyclic compression before labeling synthesized more proteoglycan.
      These segments lost a greater percent of labeled proteoglycan to medium during a
      subsequent 12-day culture period than matched segments that had not experienced
      loading. Analysis of medium and tissue proteoglycans by SDS polyacrylamide gel
      electrophoresis and sieve chromatography indicated that small proteoglycans
      (decorin and biglycan) were retained in both loaded and non-loaded tissue whereas
      large proteoglycans (migrating in the Vo of a Sepharose CL-4B column) were
      readily lost. It is concluded that the 3-day loading regimen did not diminish
      turnover of large proteoglycan. To the contrary, although synthesis of large
      proteoglycan was enhanced by the loading regimen, these proteoglycans were still
      rapidly lost from the fetal tissue.

PMID- 9023052
TI  - p53/TGF-beta/cancer: an intriguing connection.

PMID- 9023053
TI  - Trans-signaling by cytokine and growth factor receptors.
AB  - Although ligand-induced dimerization or oligomerization of receptors is a well
      established mechanism of growth factor signaling, increasing evidence indicates
      that biological responses are often mediated by receptor trans-signaling
      mechanisms involving two or more receptor systems. These include G protein
      coupled receptors, cytokine, growth factor and trophic factor receptors. Greater
      responsiveness and inhibitory signaling responses are provided when different
      signaling pathways merge through receptor trans-signaling.

PMID- 9023054
TI  - Leptin and OB-R: body weight regulation by a cytokine receptor.
AB  - There has been intense recent interest in the molecules and pathways governing
      mammalian body weight regulation. Leptin (OB), an ancestral member of the
      cytokine family, is an adipocyte-secreted circulating hormone exhibiting weight
      regulatory properties. Recently, the leptin receptor (OB-R) was identified and
      shown to exhibit sequence homology and functional similarity to members of the
      class I cytokine receptor family. The mechanisms governing OB-R triggering and
      signal transduction have begun to be elucidated, providing new insight into the
      pathways controlling mammalian body weight homeostasis.

PMID- 9023055
TI  - Functions of fibroblast growth factors in vertebrate development.
AB  - Fibroblast growth factors (FGFs) are a class of secreted polypeptide ligands
      which mediate diverse cellular responses during embryonic, fetal, and postnatal
      vertebrate development. The purposes of this review are to provide a condensed
      overview of FGFs and their receptors, to catalog and categorize the functions of
      FGFs in vertebrate development, to present recent discoveries relating to the
      interplay of FGFs with other secreted ligands in the control of tissue growth and
      patterning, and to discuss several potential directions for future research in
      the field.

PMID- 9023056
TI  - Signal transduction by members of the transforming growth factor-beta
      superfamily.
AB  - Transforming growth factor-beta (TGF beta) superfamily members exert their
      diverse biological effects through their interaction with heteromeric receptor
      complexes of transmembrane serine/threonine kinases. Both components of the
      receptor complex, known as receptor I and receptor II are essential for signal
      transduction. The composition of these complexes can vary significantly due to
      the promiscuous nature of the ligands and the receptors, and this diversity of
      interactions can yield a variety of biological responses. Several receptor
      interacting proteins and potential mediators of signal transduction have now been
      identified. Recent advances, particularly in our understanding of the function of
      Mothers against dpp-related (MADR) proteins, are providing new insights into how
      the TGF beta superfamily signals its diverse biological activities.

PMID- 9023058
TI  - Chemokine-leukocyte interactions. The voodoo that they do so well.
AB  - Leukocyte recruitment from the circulation into inflammatory tissues requires a
      series of soluble and cell-bound signals between the responding leukocyte and
      vascular endothelial barrier. Chemotactic factors are believed to be responsible
      for this selective adhesion and transmigration. A superfamily of small, soluble,
      structurally-related molecules called 'chemokines' have been identified and shown
      to selectively promote the rapid adhesion and chemotaxis of a variety of
      leukocyte subtypes both in vivo and in vitro. Chemokines are produced by almost
      every cell type in the body in response to a number of inflammatory signals, in
      particular those which activate leukocyte-endothelial cell interactions. These
      molecules also appear to play important roles in hematopoesis, cellular
      activation, and leukocyte effector functions. In addition, chemokines have been
      found in the tissues of a variety of disease states characterized by distinct
      leukocytic infiltrates, including rheumatoid arthritis, sepsis, atherosclerosis,
      asthma, psoriasis, ischemia/reperfusion injury, HIV replication, and a variety of
      pulmonary disease states. This review will primarily focus on the role of
      chemokines in cell adhesion and trafficking as well as their role as effector
      molecules.

PMID- 9023057
TI  - Stress activated cytokines and the heart.
AB  - The ability of myocardium to successfully compensate for, and adapt to, stress
      ultimately determines whether the heart will decompensate and fail, or whether it
      will instead maintain preserved function. Despite the importance of the
      myocardial response to environmental stress, very little is known with respect to
      the biochemical mechanisms that are responsible for mediating and integrating the
      stress response in the heart. In the present review we will summarize recent
      experimental material which suggests that cytokines that are expressed within the
      myocardium in response to a environment injury, namely tumor necrosis factor
      alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), may play an
      important role in initiating and integrating homeostatic responses within the
      heart. However, these 'stress-activated' cytokines all have the potential to
      produce cardiac decompensation when expressed at sufficiently high
      concentrations. Accordingly, the theme that will emerge from this discussion is
      that the short-term expression of stress-activated cytokines within the heart may
      provide the heart with an adaptive response to stress, whereas long-term
      expression of these molecules may be frankly maladaptive by producing cardiac
      decompensation.

PMID- 9023060
TI  - Treatment planning considerations for adult patients.
AB  - Orthodontic treatment planning depends on determining specific treatment
      objectives before beginning treatment. Selecting specific treatment objectives
      aids in the selection of appropriate mechanotherapy for the patient. In adult
      patients, this is particularly important. With the exception of orthognathic
      surgery, orthodontic treatment in adults must rely exclusively on tooth movement
      because no skeletal growth potential exists. Therefore, the orthodontic movements
      must be achieved with greater precision. Finally, the medical and dental
      histories of the adult patient may further increase the complexity of treatment.
      Coordinating orthodontic therapy with periodontists, restorative dentists, and
      other specialists is often necessary.

PMID- 9023059
TI  - Development, maturation, and aging of the alveolar bone. New insights.
AB  - Osteoblasts and bone tissue of the mandibular and maxillary alveolar processes
      substantially differ from osteoblasts and bone in other parts of the skeleton.
      These differences are apparent during embryonic development, maturation, and
      aging of these bones. The cellular and molecular basis for these differences is
      still not clear, but it is unfolding at record speed.

PMID- 9023061
TI  - Esthetic considerations in orthodontic treatment of adults.
AB  - Improvement in appearance is the primary reason that adults seek orthodontic
      care. Proper recognition of the dental and facial esthetic defects at the outset
      of treatment is the most important key to esthetic success and is, therefore,
      essential to satisfying the patients' needs. Division of the face and dentition
      into separate dimensions (transverse, vertical, anteroposterior) can be a useful
      way of systematically breaking down a complex problem into its component parts so
      that the optimal treatment plan can be developed for a given patient. For the
      adult patient, optimizing treatment involves a multidisciplinary team, including
      the orthodontist and general dentist and possibly an oral surgeon, a
      periodontist, and an endodontist. Proper coordination of treatment and
      communication between team members makes the difference between success and
      failure when ideal esthetics are the goal. Involvement of the patient in
      selection of alternate treatment plans will be essential to his or her
      satisfaction.

PMID- 9023062
TI  - The importance of determination of jaw position in orthodontic diagnosis and
      treatment planning for adult patients.
AB  - The basic data needed for orthodontic diagnosis and treatment planning include
      color prints of soft tissue facial profile, intraoral dental arches, and
      occlusion; cephalometric and panoramic radiographs; and dental casts. Hand-wrist
      and TMJ radiographs are also necessary in some circumstances. If orthodontic
      diagnosis and treatment plans are made only from the dental alignments and
      occlusion from the static or hand-assembled dental casts, the diagnosis and
      treatment planning made may be wrong in some cases. Clinically, it is necessary
      to find the centric relation of the lower jaw and to transfer the jaw
      relationship to the articulator. Correct diagnosis and orthodontic treatment
      planning may then be made from the findings of the occlusal relationship from the
      articulator accompanied with the information on skeletal age and craniofacial
      characteristics from the hand-wrist and cephalometric radiographs. Four clinical
      cases have been presented to demonstrate the importance of determination of jaw
      position in orthodontic diagnosis and treatment planning in adult patients.

PMID- 9023063
TI  - Correction of deep overbite in adults.
AB  - Deep overbite is one of the most common features of adult malocclusions.
      Treatment of deep overbites involves a careful diagnosis, treatment plan, and
      mechanics plan. Pure intrusion of upper or lower incisors alone or in combination
      with flaring and extrusion of posterior teeth are common methods to correct deep
      overbites. This article describes appliance systems and biomechanical
      considerations necessary for intrusion of incisors.

PMID- 9023064
TI  - Esthetic orthodontic appliances and bonding concerns for adults.
AB  - This article has described application of bonding procedures for adults in
      everyday practice. Depending on the materials and the technique employed, one can
      achieve satisfactory bonding. The techniques used to debond orthodontic brackets
      safely have been described. The bonded retainer, particularly in the mandibular
      arch, can easily be applied using the technique described. These retainers offer
      an advantage because of the high patient acceptance owing to convenience and
      esthetic reasons. Bonding on porcelain veneers and gold crowns has been
      described. Although silane pretreatment to the porcelain surface yields
      satisfactory results, the technique for bonding to gold has not yet been fully
      perfected.

PMID- 9023065
TI  - Lingual orthodontics.
AB  - The history of lingual orthodontics is discussed. Laboratory and clinical
      techniques are reviewed in detail. Two case reports with photographs are also
      included.

PMID- 9023067
TI  - Antisense confirmation of mu- and kappa-opioid receptor mediation of morphine's
      effects on body temperature in rats.
AB  - Previous studies showed that parenterally administered morphine at 4-16 mg/kg
      markedly increased body temperature in the rat, but higher doses of morphine (>
      or = 30 mg/kg, subcutaneously, sc) caused a profound decrease in body
      temperature. Based on the use of selective opioid agonists and antagonists, we
      postulated that these effects were due to morphine's actions on mu and kappa
      receptors, respectively. In the present study, we sought to determine whether an
      antisense (AS) oligodeoxynucleotide (oligo) against cloned mu or kappa opioid
      receptors could affect morphine-induced body temperature changes. AS oligos were
      directed against nucleotides 1-18 of the coding region of the mu receptor and 4
      21 of the coding region of the kappa receptor. Male SD rats were surgically
      implanted with intracerebroventricular (icv) cannulae. Rats received icv
      injections of vehicle or oligo in the animal colony room on days 1, 3 and 5.
      Either AS oligo or missense (MS) oligo was infused in a volume of 5 microliters
      over 30 s to freely moving animals. On day 6, the rats were tested. The results
      showed that icv treatment with an AS oligo against mu opioid receptors, but not
      an MS oligo against the mu opioid receptor or an AS oligo against the kappa
      opioid receptor, significantly attenuated the hyperthermia normally produced by a
      relatively low dose of morphine administered sc. In addition, treatment with an
      AS oligo against kappa receptors, but not an MS oligo against kappa opioid
      receptor or an AS oligo against the mu opioid receptor, significantly blocked the
      hypothermia induced by a high dose of morphine. This study confirms our earlier
      postulate that morphine at 4 mg/kg, sc, induces an increase in body temperature
      primarily via mu opioid receptors in the brain and a high dose (30 mg/kg) of
      morphine administered sc produces a decrease primarily through kappa opioid
      receptors in the brain.

PMID- 9023068
TI  - Development of an adherence/competence rating scale for individual drug
      counseling.
AB  - This paper reports on the development of a 43 item rating scale that assesses
      therapist adherence and competence in individual drug counseling (IDC) for the
      treatment of cocaine dependence. Three independent judges rated 41 audiotaped IDC
      sessions from the pilot/training phase of the NIDA collaborative cocaine study.
      Judges also rated 11 tapes of Cognitive sessions and ten tapes of Supportive
      Expressive psychodynamic sessions. Interjudge reliability for the total scale
      score and subscales ranged from 0.55 to 0.89 and internal consistency
      coefficients ranged from 0.43 to 0.95. Ratings indicated that IDC counselors used
      IDC techniques more frequently and competently than did therapists from other
      modalities.

PMID- 9023069
TI  - Characterization of the decline in alcohol consumption by aminopeptidase
      inhibition.
AB  - Bestatin, an aminopeptidase inhibitor, prolongs the action of angiotensin and
      enkephalin. Previous studies have shown that bestatin can reduce alcohol intake
      in heterogeneous as well as genetically selected alcohol preferring 'P' rats, but
      more detailed studies of the characteristics of this effect have not yet been
      done. In experiment 1, daily injections of 10, 20 or 40 mg/kg bestatin for 12
      days produced a uniform reduction in alcohol intake (approximately 40%) which did
      not recover following suspension of bestatin, but did recover following a 7 day
      period of morphine-stimulated alcohol drinking. In experiment 2, the lower end of
      the dose range was explored (2.5, 5, 10 mg/kg) and a dose-dependent effect was
      observed with a threshold dose of 5 mg/kg. Again, alcohol drinking did not
      recover following suspension of the 10 mg/kg dose of bestatin. Using a limited
      access procedure, bestatin reduced the intake of a preferred sodium chloride
      solution but not an avidly-consumed glucose solution indicating that while
      bestatin's effect was selective, it was not specific to alcohol. In the final
      experiment, the role of angiotensin and enkephalin was explored by pretreating
      animals with losartan (5, 10, 20 mg/kg), an angiotensin receptor blocker and
      naltrexone, (0.25, 0.5, 1 mg/kg) an opiate receptor blocker. Both agents produced
      significant but rather small attenuations in bestatin's effect suggesting that
      other factors are involved in its action. These findings further characterize the
      inhibitory effect of bestatin on alcohol intake in rodents. In addition, the
      novel finding of a carry-over inhibition of alcohol intake in the bestatin-free
      period adds further impetus to the recommendation that this drug, which has been
      safely used in humans, might be examined as a possible therapeutic agent for
      alcohol abuse.

PMID- 9023070
TI  - Age-specific patterns of hallucinogen use in the US population: an analysis using
      generalized additive models.
AB  - Although there has been growing concern in recent years about an escalation in
      the use of LSD and other hallucinogens, little is known about the distribution of
      the use of these drugs in the United States population. In order to fill this
      gap, we used generalized additive models to analyze data from the 1988, 1990, and
      1992 National Household Survey on Drug Abuse, to compare the age-specific
      prevalence of hallucinogen use by level of socio-economic indicators. In
      addition, we used survival analysis to compare patterns in the onset of use. Use
      of hallucinogens in the past year was highest at the age of 19 years for each of
      the NHSDA surveys, but use was not linked to enrollment in school at this age.
      Past year prevalence was highest among whites and respondents with high family
      income. The onset of hallucinogen use was most likely to occur between ages 15-19
      years, regardless of birth cohort. These results indicate a stable pattern since
      hallucinogens were made widely available in the late 1960s, in which the
      transition from adolescence to adulthood has been the period of highest risk for
      hallucinogen use.

PMID- 9023071
TI  - Neighborhood environment and opportunity to use cocaine and other drugs in late
      childhood and early adolescence.
AB  - We hypothesized that neighborhood disadvantage might function as a determinant of
      "exposure opportunity', an intermediate step on a path toward starting to use
      drugs illicitly. Testing this hypothesis, we analyzed self-report data gathered
      in 1992 by means of confidential interviews with 1416 urban-dwelling middle
      school participants in a longitudinal field study. Within this epidemiologic
      sample, 50 youths said that someone actively had offered them a chance to take
      cocaine or smoke crack; tobacco had been offered to 395 youths; alcohol to 429
      youths. Using multiple logistic regression to hold constant grade, sex, minority
      status, and peer drug use, we found a moderately potent association between
      neighborhood disadvantage and exposure to cocaine: youths living in the most
      disadvantaged neighborhoods (highest tertile) were an estimated 5.6 times more
      likely to have been offered cocaine, as compared to those in relatively
      advantaged neighborhoods (P = 0.001). By comparison, there were weaker but
      statistically significant associations involving tobacco exposure opportunity
      (odds ratio, OR = 1.7, P = 0.004) and alcohol exposure opportunity (OR = 1.9, P =
      0.0005). Future research will clarify the etiologic significance of neighborhood
      disadvantage in pathways leading toward illicit drug use.

PMID- 9023072
TI  - Outcome of a second episode of methadone maintenance.
AB  - This paper reports the treatment progress of methadone maintenance clients who
      were discharged or withdrew from treatment and then were readmitted for a second
      episode of treatment. Thirty-nine clients in a contingency contract condition
      remained in treatment long enough (6 months) during both the initial and a second
      treatment episode, to be exposed to discharge sanctions that were part of the
      contingency contract. Of these clients 34 failed treatment during the initial
      treatment episode. Nine (26%) of these initial treatment failures improved their
      performance in the second episode compared to the first, and only one (20%) of
      five initial treatment successes who left treatment during their first treatment
      episode for non-contract reasons showed a poorer performance (failing the second
      after succeeding in the first episode). Of 17 clients in a condition that applied
      no contingencies for positive urines, three of 14 (21%) who failed during the
      initial treatment episode improved their performance, and two of three (67%) who
      succeeded during the initial treatment episode failed in the second episode. For
      a subset of clients the efficacy of contingency contracting may not be realized
      until it is reapplied during a subsequent admission.

PMID- 9023073
TI  - Intrathecally administered flumazenil and PK 11195 precipitate abstinence
      syndrome in freely moving diazepam dependent rats.
AB  - The central and peripheral benzodiazepine (BZ) receptor antagonists, flumazenil
      (FLU) and PK 11195 (PK), administered intrathecally (IT) to diazepam (DZ)
      dependent rats produced a precipitated abstinence syndrome. The scores for
      abstinence increased with increasing dose of FLU but not with increasing dose of
      PK. Twitches and jerks increased with increased doses of both. Head and body
      tremors were produced by FLU, but not by PK. Neither FLU nor PK precipitated
      abstinence in controls. In DZ-dependent rats IT administered FLU and PK did not
      significantly change the spectral content and the total power of the EEG. The
      data indicate that an abstinence syndrome is precipitated at the spinal level in
      DZ-dependent rats and that both central and peripheral BZ receptors are involved.

PMID- 9023074
TI  - Gender differences among opioid abusers: pathways to disorder and profiles of
      psychopathology.
AB  - This study focused on gender differences in childhood disorders and severity of
      adult psychosocial impairment among 106 females and 95 males seeking treatment
      for opiate addiction. Results indicated that as compared to males, female addicts
      reported significantly lower levels of conduct problems and higher levels of
      internalizing problems during childhood; these differences held even after
      controlling for comorbid adult psychiatric diagnosis. Findings also revealed that
      female addicts were at a disadvantage relative to males in terms of overall
      severity of psychiatric distress. Concomitantly, however, females showed less
      social deviance-on a range of illegal behaviors-as compared to men. Results were
      discussed in terms of implications for treatment planning: they underscore the
      need to consider gender differences in pathways to, and nature of, adult
      psychopathology among addicted individuals.

PMID- 9023075
TI  - Prevalence and correlates of the injection of methadone syrup in Sydney,
      Australia.
AB  - A sample of 312 heroin users was interviewed on their injection of methadone
      syrup. Methadone injecting was widespread, with 52% of subjects having injected
      methadone syrup, 29% in the preceding six months. Males and females were equally
      likely to report methadone injecting. Forty per cent of current methadone
      injectors reported weekly or more frequent methadone injecting over the preceding
      six months. A history of methadone injecting was associated with abscesses and
      infections in injection sites, having been diagnosed with a venous thrombosis and
      a history of heroin overdose. Current methadone injectors were in poorer general
      health, had more injection-related symptoms, higher levels of psychological
      distress, were more likely to have recently passed on used injecting equipment
      and to have recently committed criminal acts. Implications for the reduction in
      the prevalence of methadone injecting and associated harm are discussed.

PMID- 9023076
TI  - Ramification of microglia, monocytes and macrophages in vitro: influences of
      various epithelial and mesenchymal cells and their conditioned media.
AB  - Microglial cells are able to switch between an "active" amoeboid and a ramified
      "resting" morphology during development and after experiencing lesions. We have
      previously shown that in vitro microglial morphology is controlled by their
      cellular environment, i. e. cells become ramified in astrocyte coculture but
      amoeboid on monolayers of fibroblasts. In the present study we have extended the
      analysis of the control of macrophage morphology by maintaining macrophages of
      different origins in coculture with different epithelial or mesenchymal cells and
      their conditioned media. Microglia, monocytes and spleen macrophages seeded onto
      monolayers of astrocytes, kidney epithelia or hepatoma cells developed the
      ramified morphology but remained amoeboid in fibroblast coculture. Ramification
      was also induced by media conditioned by these cells as well as by phorbolic
      esters, i.e. activators of protein kinase C. In double coculture assays, even
      small numbers of fibroblasts were able to override the "epithelial" influence.
      Likewise, microglia remained amoeboid, when incubated on several constituents of
      the extracellular matrix. These results indicate that macrophage ramification is
      an active process initiated by diffusible factors secreted by various epithelial
      cells, possibly acting upon a protein-kinase-C-related receptor. We interprete
      the modification of macrophage morphology as a functional adaptation to the
      surrounding type of tissue that is enforced by its constituent cells. Thus, the
      specific morphologies of microglia, hepatic von Kupffer's cells or peritubular
      kidney macrophages could be explained by similar epithelium-macrophage
      interaction.

PMID- 9023077
TI  - Influence of elevated expression of rat wild-type PMP22 and its mutant
      PMP22Trembler on cell growth of NIH3T3 fibroblasts.
AB  - The peripheral myelin gene PMP22 is the rat and human homologue of the murine
      growth-arrest-specific gene gas3. The biological function of PMP22 is unknown,
      but recent progress in the analysis of rat Schwann cells expressing altered
      levels of PMP22 revealed that one role of PMP22 is as a negative growth
      modulator. We have investigated the influence of rat PMP22 (rPMP22) and a mutant
      of PMP22 (rPMP22(Tr)) resembling the murine trembler mutation on cell growth of
      retrovirus-vector-infected mouse NIH3T3 cells. Transduced cells carrying the two
      different sense constructs expressed rPMP22 and rPMP22(Tr )mRNAs and proteins.
      Elevated levels of rPMP22 and rPMP22(Tr )significantly reduced fibroblast growth
      as judged by proliferation assays. Despite a negative modulatory influence of
      rPMP22 and rPMP22(Tr )on cell proliferation, cell cycle analyses by flow
      cytometry did not reveal an influence of rPMP22 or rPMP22(Tr )on the synchronous
      progression of resting NIH3T3 cells from G0 into S phase. However, cell cycle
      analyses by flow cytometry of asynchronously dividing cultures demonstrated that
      the expression of rPMP22 and rPMP22(Tr )increased the fraction of cells in the G1
      phase of the cell cycle. Furthermore, cell death analyses revealed that, in
      contrast to control cells and cells carrying the rPMP22(Tr )construct, a
      significantly increased fraction of NIH3T3 cells expressing rPMP22 exit the
      proliferation compartment showing hallmarks of programmed cell death. These
      results indicate that (i) rPMP22 and rPMP22(Tr )act as negative modulators of
      proliferation in murine fibroblasts probably through extension of the G1 phase of
      the cell cycle and (ii) rPMP22 but not rPMP22(Tr )promotes programmed death of
      these cells.

PMID- 9023078
TI  - Fibroblast growth factor-2 (FGF-2) and FGF-receptor (FGFR-1) immunoreactivity in
      embryonic spinal autonomic neurons.
AB  - The development of the nervous system appears to be under the control of multiple
      growth factors, neurotrophins and cytokines, which may be expressed either
      continuously or transiently throughout defined stages of cellular generation,
      proliferation or differentiation. Fibroblast growth factor (FGF) cytokines and
      their receptors are abundantly expressed in the embryonic nervous system but
      their localization at autonomic levels in the fetal spinal cord has not yet been
      detailed. Immunoreactivity to FGF-2, probably the best characterized member of
      the FGF family (FGF-1 to FGF-10) and of one of its high affinity receptors, FGFR
      1, was found in autonomic neurons at embryonic day E14, the peak day of
      generation and proliferation in the common ventral motoneuron pool. It was also
      continuously present throughout the investigated subsequent stages (E15 to
      postnatal day P30). Immunogold electron microscopy revealed the cytoplasmic
      localization of FGF-2 and FGFR-1 in intermediolateral neurons, the major group of
      sympathetic preganglionic neurons in the spinal cord. In these neurons,
      immunocytochemistry from E14 onwards showed the co-distribution of both markers
      at the period of axonal outgrowth to peripheral targets, e.g. the adrenal
      medulla. Our findings suggest autocrine and/or paracrine actions of FGF-2 for
      sympathetic preganglionic development but do not support its role as a target
      derived neurotrophic factor for autonomic neuron development.

PMID- 9023079
TI  - Oxytocin innervation of spinal preganglionic neurons projecting to the superior
      cervical ganglion in the rat.
AB  - The paraventricular nucleus of the hypothalamus is a major integrative nucleus
      for relaying information from the suprachiasmatic nucleus to the autonomic
      system. The precise pathway by which this information can influence autonomic
      functions, such as melatonin synthesis in the pineal gland, is not clear. In the
      present study, we used a retrograde tracer injected in the superior cervical
      ganglion to identify spinal preganglionic neurons. One of the main
      neurotransmitters present in descending projections of the paraventricular
      nucleus of the hypothalamus, oxytocin, was detected with immunocytochemistry to
      visualise possible contacts with the neurons located in the intermediolateral
      column of the spinal cord and projecting to the superior cervical ganglion.
      Although many appositions could be seen at the light-microscopic level, this
      abundance could not be confirmed at the electron-microscopic level. The
      implications of these observations for the overall timing message received by the
      spinal preganglionic neurons are discussed.

PMID- 9023080
TI  - The distribution of GABA and glycine immunostaining in the cochlear nucleus of
      the mustached bat (Pteronotus parnellii).
AB  - The distribution of neuronal elements immunoreactive for gamma-aminobutyric acid
      (GABA) and glycine in the cochlear nucleus of the mustached bat Pteronotus
      parnellii has been studied by means of the postembedding technique on serial
      semithin sections. Our goal has been to identify similarities and differences in
      the organization of putatively inhibitory circuits between a highly specialized
      echolocating bat and previously studied non-echolocating mammals. The results
      reveal a basically conserved pattern of putatively GABAergic and glycinergic
      elements in the bat cochlear nucleus, and subtle but distinct modifications in
      certain inhibitory circuits. As in other mammals, immunoreactive cells possibly
      representing local interneurons are most abundant in the dorsal cochlear nucleus.
      These include single-GABA-immunoreactive cells and double-labeled cells in the
      superficial layers and single-glycine-labeled cells in the deep layers.
      Coincident with the phylogenetic trend toward a reduced lamination of the dorsal
      cochlear nucleus in bats, there is a clear reduction in the numbers of local
      interneurons of the superficial layer. In contrast, the tuberculoventral system
      of the deep layer appears hypertrophied. As in other mammals, the ventral
      cochlear nucleus contains a few large single-glycine-immunoreactive cells and
      scattered double-labeled cells. Immunoreactive puncta are abundant throughout the
      cochlear nucleus complex with no trends indicating a differential strength of
      inhibitory inputs to regions representing the various harmonics of the
      echolocating signal.

PMID- 9023081
TI  - Expression and characterization of the "laminin binding protein" in hydra.
AB  - Recently, a cDNA was isolated from hydra with extensive homology to a mammalian
      and invertebrate gene which codes for a protein called laminin binding protein
      (LBP). In this paper we describe the protein expression of the hydra LBP in
      Escherichia coli. On SDS gels the recombinant hydra LBP displayed an apparent
      molecular mass of 43 kDa, although the calculated mass, including six additional
      histidines, is 33.7 kDa. Polyclonal antibodies were produced against the hydra
      recombinant LBP. The antiserum reacted with a 42-kDa and a 43-kDa protein from
      Hydra vulgaris and from a multiheaded mutant of Chlorohydra viridissima,
      respectively. In hydra, LBP RNA and protein were highly expressed in cells with
      short cell cycles, such as all cells of the interstitial cell lineage, less in
      slowly cycling epithelial cells, and at very reduced levels or not at all in
      differentiated cells. Higher expression in the multiheaded mutant of C.
      viridissima than in H. vulgaris, the cells of which differ in doubling time, hint
      at a function in cell proliferation. This is supported by the finding that in
      vitro hydra LBP is a substrate for the cell-cycle-specific kinase CDC2. 

PMID- 9023082
TI  - 5-HT-like immunoreactivity in the brains of plethodontid and salamandrid
      salamanders (Hydromantes italicus, Hydromantes genei, Plethodon jordani,
      Desmognathus ochrophaeus, Pleurodeles waltl): an immunohistochemical and biocytin
      double-labelling study.
AB  - The distribution of 5-HT-like-immunoreactive cell bodies and fibres was studied
      in the brains of the salamanders Hydromantes italicus, H. genei, Plethodon
      jordani, Desmognathus ochrophaeus (family Plethodontidae), and Pleurodeles waltl
      (family Salamandridae). In addition, double-labelling experiments with biocytin
      were carried out to identify the relationship between serotonergic fibres and
      neurons involved in the processing of sensory and sensorimotor information. In
      all species, 5-HT-immunopositive somata are found in the ventral thalamus close
      to the ventricle forming the paraventricular organ. In the hypothalamus, cells
      are labelled in the ependymal layer around the infundibular recess and at the
      lateral edge of the periventricular grey. In the pretectum, a few immunoreactive
      cells are situated dorsolaterally in the grey matter. In the tegmentum and
      medulla oblongata, cells of the raphe nuclei are regularly distributed along the
      midline; labelled perikarya are occasionally found in the cervical spinal cord. 5
      HT-like-immunoreactive fibres are widely distributed throughout the nervous
      system. Densely arborizing fibres are found in the olfactory bulb, striatum and
      amygdala. Distinct fibre projections extend in the ventral thalamus and tectum.
      Biocytin tracing of striatal and tectal projection neurons and ascending
      reticular neurons combined with the demonstration of 5-HT suggest that the
      striatum, the tectum and the ascending activating system are strongly influenced
      by 5-HT. 

PMID- 9023083
TI  - Anally projecting neurons exhibiting immunoreactivity to galanin, nitric oxide
      synthase and vasoactive intestinal peptide, detected by confocal laser scanning
      microscopy, in the intestine of the Atlantic cod, Gadus morhua.
AB  - The projections of enteric neurons showing immunoreactivity for vasoactive
      intestinal peptide (VIP), nitric oxide synthase (NOS) and galanin were
      investigated in the myenteric plexus of the intestine of the Atlantic cod, Gadus
      morhua. Quantification of immunoreactive material on the proximal and distal side
      of a myotomy was performed by means of confocal laser scanning microscopy. NOS
      immunoreactivity was reduced anal to the myotomy, whereas there was an
      accumulation of immunoreactivity for VIP and for galanin oral to the cut. These
      results suggest the presence of VIP, NOS and galanin in neurons with oral-to-anal
      projections along the intestine of the cod. Since descending neurons in the
      myenteric plexus of many other vertebrates also contain these substances, we
      conclude that the oral-to-anal projections of neurons containing VIP, NOS and
      galanin are highly conserved features and important for the descending phase of
      intestinal peristalsis on an evolutionary basis. 

PMID- 9023084
TI  - Growth hormone as an in vitro phagocyte-activating factor in the gilthead sea
      bream (Sparus aurata).
AB  - The stimulatory action of growth hormone on gilthead sea bream phagocyte-enriched
      cultures was demonstrated in vitro for the first time in a fish species.
      Phagocytes consisted mainly of macrophages, with a small number of neutrophils
      and eosinophils. Macrophages were unequivocally identified by their esterase
      staining and the lack of myeloperoxidase staining. Cells primed with recombinant
      rainbow trout GH showed clear morphological (light- and scanning electron
      microscopic) and functional differences from non-primed cells. Stimulated
      phagocytes exhibited numerous branched lamellipodia, abundant membrane ruffles,
      increased spreading, and cell size. When incubated with sheep red blood cells,
      the phagocytic index and phagocytic capacity was also enhanced in primed cells. A
      bell-shaped dose-response curve (1.5-500 nM) was obtained when the metabolic
      activity of growth-hormone-activated cells was measured. This finding suggests
      that the homodimerization of the growth hormone receptor is a characteristic
      feature both in mammals and fish. 

PMID- 9023085
TI  - Crustacean hyperglycaemic hormone in the nervous system of the primitive
      crustacean species Daphnia magna and Artemia salina (Crustacea: Branchiopoda).
AB  - Crustacean hyperglycaemic hormone-immunoreactive neuronal systems are detected in
      the central and peripheral nervous systems of two entomostracan crustaceans,
      Daphnia magna and Artemia salina, by immunocytochemistry using specific antisera
      against crustacean hyperglycaemic hormones of the decapod crustaceans Orconectes
      limosus and Carcinus maenas. In D. magna, four small putative interneurones are
      detected in the brain. In the thorax, ten bipolar peripheral neurones are stained
      by both antisera. They are obviously segmental homologues with centrally
      projecting axons that form interdigitating varicose fibres and terminals in
      putative neurohaemal areas next to the surface of the anterior part of the
      thoracic ganglia. Similar immunopositive neurones occur both in the central and
      peripheral nervous systems of A. salina. A total of five groups of neurones occur
      in the protocerebrum, the deutocerebrum and the mandibular ganglion. Some of the
      protocerebral neurones are bipolar and project to the dorsal frontal organ. A
      single pair of peripheral multipolar neurones in the maxillary segment projects
      centrally into the ventral nerve cord and innervates unidentified somatic muscles
      and tissues in the maxillary and the first appendage segments. None of the brain
      neurones in both species show similarities to decapod X-organ sinus gland
      neurosecretory neurones. Chromatography of brain extracts of D. magna combined
      with immunodot blotting revealed two strongly immunoreactive fractions at
      retention times close to that of the crustacean hyperglycaemic hormone of
      crayfish. Moreover, preabsorption controls suggest that the cross-reacting
      peptides of D. magna and A. salina are structurally closely related to those of
      decapods. 

PMID- 9023086
TI  - Is there an orientation-dependent excursion of the Muller body in the
      "statocystoid" of Loxodes?
AB  - The ciliate Loxodes possesses a number of vesicles at its anterior dorsal margin.
      These so-called Muller vesicles contain a spherical inclusion (Muller body) in
      which lie crystals of barium salts. The Muller body is connected via a stalk to
      the wall of its vesicle. It is presumed to function as a stato-organelle and to
      respond by visible motions to changes of the direction of gravity. We have
      attempted to document the motion of the Muller body with respect to the direction
      of the gravity vector. Living cells moving in a horizontal or a vertical plane
      have been viewed under the light microscope with differential interference
      contrast, documented on video film, and sequences of single frames have been
      evaluated. Apparent excursions of the Muller body by about 1.5 MUm, corresponding
      to a deviation of 10 degrees  at the base of the stalk, are observed in cells
      moving in a horizontal plane. No larger excursions have been seen in the vertical
      plane. Implications of this result for a model of the stato-organelle are
      discussed.

PMID- 9023087
TI  - Time course of mitosis and collateral growth following coronary microembolization
      in the porcine heart.
AB  - In ischaemic porcine myocardium, the growth of collateral vessels by angiogenesis
      is observed in clusters in the vicinity of focal necroses. Because mitosis of
      endothelial cells is a prerequisite for angiogenesis, the purpose of this study
      has been to evaluate the time course of mitosis as an indicator of vascular
      growth in a porcine model of coronary microembolization. Ischaemia was induced by
      injection of 25-microm microspheres in the left circumflex artery, followed by
      tissue collection from non-ischaemic and ischaemic areas of the same heart after
      24, 72 or 168 h microembolization. Tissue was studied by histone H3 in-situ
      hybridization, PCNA/cyclin immunohistochemistry and electron microscopy. The
      number of blood vessels in ischaemic myocardium was compared with that in normal
      control tissue. Capillary growth started as early as 24 h after
      microembolization, as indicated by increasing numbers of proliferating, histone
      H3- and PCNA/cyclin-positive cells in the necrotic inflammatory foci of the
      ischaemic area. At 72 h and 168 h, the number of blood vessels was significantly
      higher in ischaemic than in normal myocardium, whereas at 168 h, mitosis of cells
      was, as in normal myocardium, a rare event. Coronary microembolization of porcine
      myocardium thus leads to an increased cellular proliferation rate between 24 h
      and less than 7 days after the onset of microembolization, followed by enhanced
      capillary growth. In-situ hybridization with histone H3 and PCNA/cyclin
      immunohistochemistry seem to be reliable markers for proliferation and vascular
      growth in non-cancerogenic tissue.

PMID- 9023089
TI  - Microdeletions in the Y chromosome of infertile men.
AB  - BACKGROUND: Some infertile men with azoospermia or severe oligospermia have small
      deletions in regions of the Y chromosome. However, the frequency of such
      microdeletions among men with infertility in general is unknown. We sought to
      determine the prevalence of Y-chromosome microdeletions among infertile men and
      to correlate the clinical presentation of the men with specific deletions.
      METHODS: We studied 200 consecutive infertile men. Each man was evaluated
      comprehensively for known causes of infertility, and Y-chromosome microdeletions
      were studied with use of the polymerase chain reaction to amplify specific
      regions of the chromosome. The Y chromosomes of 200 normal men were also
      analyzed. RESULTS: Fourteen infertile men (7 percent) and four normal men (2
      percent) had microdeletions of the Y chromosome. Nine of the infertile men had
      azoospermia or severe oligospermia (sperm concentration, <5 million per
      milliliter), four had oligospermia (sperm concentration, 5 million to <20 million
      per milliliter), and one had normospermia (sperm concentration, > or = 20 million
      per milliliter). The size and location of the deletions varied and did not
      correlate with the severity of spermatogenic failure. The fathers of six
      infertile men with microdeletions were studied; two had the same deletions as
      their sons, and four had no deletions. CONCLUSIONS: A small proportion of men
      with infertility have Y-chromosome microdeletions, but the size and position of
      the deletions correlate poorly with the severity of spermatogenic failure, and a
      deletion does not preclude the presence of viable sperm and possible conception.

PMID- 9023091
TI  - Life-threatening Cache Valley virus infection.

PMID- 9023090
TI  - Treatment of traumatic brain injury with moderate hypothermia.
AB  - BACKGROUND: Traumatic brain injury initiates several metabolic processes that can
      exacerbate the injury. There is evidence that hypothermia may limit some of these
      deleterious metabolic responses. METHODS: In a randomized, controlled trial, we
      compared the effects of moderate hypothermia and normothermia in 82 patients with
      severe closed head injuries (a score of 3 to 7 on the Glasgow Coma Scale). The
      patients assigned to hypothermia were cooled to 33 degrees C a mean of 10 hours
      after injury, kept at 32 degrees to 33 degrees C for 24 hours, and then rewarmed.
      A specialist in physical medicine and rehabilitation who was unaware of the
      treatment assignments evaluated the patients 3, 6, and 12 months later with the
      use of the Glasgow Outcome Scale. RESULTS: The demographic characteristics and
      causes and severity of injury were similar in the hypothermia and normothermia
      groups. At 12 months, 62 percent of the patients in the hypothermia group and 38
      percent of those in the normothermia group had good outcomes (moderate, mild, or
      no disabilities). The adjusted risk ratio for a bad outcome in the hypothermia
      group was 0.5 (95 percent confidence interval, 0.2 to 1.2). Hypothermia did not
      improve the outcomes in the patients with coma scores of 3 or 4 on admission.
      Among the patients with scores of 5 to 7, hypothermia was associated with
      significantly improved outcomes at 3 and 6 months (adjusted risk ratio for a bad
      outcome, 0.2; 95 percent confidence interval, 0.1 to 0.9 at both intervals),
      although not at 12 months (risk ratio, 0.3; 95 percent confidence interval, 0.1
      to 1.0). CONCLUSIONS: Treatment with moderate hypothermia for 24 hours in
      patients with severe traumatic brain injury and coma scores of 5 to 7 on
      admission hastened neurologic recovery and may have improved the outcome.

PMID- 9023092
TI  - Images in clinical medicine. Digoxin-induced bidirectional ventricular
      tachycardia.

PMID- 9023093
TI  - Differences in the use of psychiatric outpatient services between the United
      States and Ontario.
AB  - BACKGROUND: The relation between health insurance and the use of mental health
      services is unclear. We compared the use of outpatient services for psychiatric
      problems in the United States and Ontario, Canada, among young and middle-aged
      adults according to self-reports of disorders listed in the Diagnostic and
      Statistical Manual of Mental Disorders (third edition, revised) and to other
      indicators of need. METHODS: We analyzed two general-population surveys carried
      out separately in the United States and Ontario in 1990 that used identical
      assessments of need for services and questions about their use by persons 15 to
      54 years of age. RESULTS: Respondents in the United States were significantly
      more likely than those in Ontario to report having had psychiatric disorders,
      poor mental health, or workdays lost or cut short because of psychiatric problems
      in the previous year. A significantly higher proportion of respondents in the
      United States (13.3 percent) than in Ontario (8.0 percent) had obtained
      outpatient treatment in the previous 12 months for psychiatric problems. However,
      an analysis of subgroups found that the higher probability of the use of services
      in the United States was confined to people with less severe mental illness. The
      average number of visits did not differ significantly between the two countries
      among patients who had similar numbers of psychiatric disorders over the same
      time periods. There was a stronger match in Ontario than in the United States
      between the use of services and the measures of perceived need we considered.
      CONCLUSIONS: Although the mental health care system in the United States provides
      treatment to a larger proportion of the population than that in Ontario, the
      match between some measures of need and treatment is not as strong in the United
      States. Any plans to expand coverage for psychiatric disorders in the United
      States must address this problem.

PMID- 9023094
TI  - The management of Paget's disease of bone.

PMID- 9023095
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 6-1997. A 69-year-old man with a complex medical history and
      severe abdominal pain.

PMID- 9023096
TI  - End of the oldest controversy in medicine. Are we ready to conclude the debate on
      digitalis?

PMID- 9023097
TI  - The Y chromosome and spermatogenesis.

PMID- 9023098
TI  - Improving outpatient psychiatric care.

PMID- 9023099
TI  - The English sweating sickness, 1485 to 1551.

PMID- 9023100
TI  - Comparison of picornaviral IRES-driven internal initiation of translation in
      cultured cells of different origins.
AB  - We recently compared the efficiency of six picornaviral internal ribosome entry
      segments (IRESes) and the hepatitis C virus (HCV) IRES for their ability to drive
      internal initiation of translationin vitro. Here we present the results of a
      similar comparison performed in six different cultured cell lines infected with a
      recombinant vaccinia virus expressing the T7 polymerase and transfected with
      dicistronic plasmids. The IRESes could be divided into three groups: (i) the
      cardiovirus and aphthovirus IRESes (and the HCV element) direct internal
      initiation efficiently in all cell lines tested; (ii) the enterovirus and
      rhinovirus IRESes are at least equally efficient in several cell lines, but are
      extremely inefficient in certain cell types; and (iii) the hepatitis A virus IRES
      is incapable of directing efficient internal initiation in any of the cell lines
      used (including human hepatocytes). These are the same three groups found when
      IRESes were classified according to their activitiesin vitro, or according to
      sequence homologies. In a mouse neuronal cell line, the poliovirus and other type
      I IRESes were not functional in an artificial bicistronic context. However,
      infectious poliovirions were produced efficiently after transfection of these
      cells with a genomic length RNA. Furthermore, activity of the type I IRESes was
      dramatically increased upon co-expression of the poliovirus 2A proteinase,
      demonstrating that while IRES efficiency may vary considerably from one cell type
      to another, at least in some cases viral proteins are capable of overcoming cell
      specific translational defects.

PMID- 9023101
TI  - Abasic site binding by the human apurinic endonuclease, Ape, and determination of
      the DNA contact sites.
AB  - The mutagenic and lethal effects of abasic sites in DNA are averted by repair
      initiated by 'class II' apurinic (AP) endonucleases, which cleave immediately
      5'to abasic sites. We examined substrate binding by the human AP endonuclease,
      Ape protein (also called Hap1, Apex or Ref-1). In electrophoretic mobility-shift
      experiments, Ape bound synthetic DNA substrates containing single AP sites or
      tetrahydrofuran (F) residues. No complexes were detected with single-stranded
      substrates or unmodified duplex DNA. In EDTA, the concentration of Ape required
      to shift 50% of duplex F-DNA was approximately 50 nM, while the addition of 10 mM
      MgCl2 nearly eliminated detectable F-DNA@Ape complexes. Filter-binding studies
      demonstrated a half-life of approximately 50 s at 0 degrees C for F-DNA@Ape
      complexes in the presence of EDTA, and <15 s after the addition of Mg2+. The DNA
      recovered from F-DNA@Ape complexes was intact but was rapidly cleaved upon
      addition of Mg2+, which suggests that these protein-DNA complexes are on the
      catalytic pathway for incision. Methylation and ethylation interference
      experiments identified DNA contacts critical for Ape binding, and Cu-1, 10
      phenanthroline footprinting suggested an Ape-induced structural distortion at the
      abasic site prior to cleavage.

PMID- 9023102
TI  - Forced evolution of a regulatory RNA helix in the HIV-1 genome.
AB  - The 5'and 3'end of the HIV-1 RNA genome forms a repeat (R) element that encodes a
      double stem-loop structure (the TAR and polyA hairpins). Phylogenetic analysis of
      the polyA hairpin in different human and simian immunodeficiency viruses suggests
      that the thermodynamic stability of the helix is fine-tuned. We demonstrated
      previously that mutant HIV-1 genomes with a stabilized or destabilized hairpin
      are severely replication-impaired. In this study, we found that the mutant with a
      destabilized polyA hairpin structure is conditionally defective. Whereas reduced
      replication is measured in infections at the regular temperature (37 degrees C),
      this mutant is more fit than the wild-type virus at reduced temperature (33
      degrees C). This observation of a temperature-dependent replication defect
      underscores that the stability of this RNA structure is critical for function. An
      extensive analysis of revertant viruses was performed to further improve the
      understanding of the critical sequence and structural features of the element
      under scrutiny. The virus mutants with a stabilized or destabilized hairpin were
      used as a starting point in multiple, independent selections for revertant
      viruses with compensatory mutations. Both mutants reverted to hairpins with wild
      type stability along various pathways by acquisition of compensatory mutations.
      We identified 19 different revertant HIV-1 forms with improved replication
      characteristics, providing a first look at some of the peaks in the total
      sequence landscape that are compatible with virus replication. These experiments
      also highlight some general principles of RNA structure building.

PMID- 9023103
TI  - The structure of 3'-O-anthraniloyladenosine, an analogue of the 3'-end of
      aminoacyl-tRNA.
AB  - 3'-O-Anthraniloyladenosine, an analogue of the 3'- terminal aminoacyladenosine
      residue in aminoacyl-tRNAs, was prepared by chemical synthesis, and its crystal
      structure was determined. The sugar pucker of 3'-O-anthraniloyladenosine is 2'
      endo resulting in a 3'-axial position of the anthraniloyl residue. The nucleoside
      is insynconformation, which is stabilized by alternating stacking of adenine and
      benzoyl residues of the neighboring molecules in the crystal lattice. The
      conformation of the 5'-hydroxymethylene in 3'-O- anthraniloyladenosine is gauche
      gauche. There are two intramolecular and two intermolecular hydrogen bonds and
      several H-bridges with surrounding water molecules. The predominant structure of
      3'-O-anthraniloyladenosine in solution, as determined by NMR spectroscopy, is 2'
      endo,gauche-gauche and anti for the sugar ring pucker, the torsion angle around
      the C4'-C5'bond and the torsion angle around the C1'-N9 bond, respectively. The
      2'-endo conformation of the ribose in 2'(3')-O-aminoacyladenosine, which places
      the adenine and aminoacyl residues in equatorial and axial positions,
      respectively, could serve as a structural element that is recognized by enzymes
      that interact with aminoacyl-tRNA or by ribosomes to differentiate between
      aminoacylated and non-aminoacylated tRNA.

PMID- 9023104
TI  - tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic
      sequence.
AB  - We describe a program, tRNAscan-SE, which identifies 99-100% of transfer RNA
      genes in DNA sequence while giving less than one false positive per 15 gigabases.
      Two previously described tRNA detection programs are used as fast, first-pass
      prefilters to identify candidate tRNAs, which are then analyzed by a highly
      selective tRNA covariance model. This work represents a practical application of
      RNA covariance models, which are general, probabilistic secondary structure
      profiles based on stochastic context-free grammars. tRNAscan-SE searches at
      approximately 30 000 bp/s. Additional extensions to tRNAscan-SE detect unusual
      tRNA homologues such as selenocysteine tRNAs, tRNA-derived repetitive elements
      and tRNA pseudogenes.

PMID- 9023105
TI  - Xp54, the Xenopus homologue of human RNA helicase p54, is an integral component
      of stored mRNP particles in oocytes.
AB  - In investigating the composition of stored (maternal) mRNP particles in Xenopus
      oocytes, attention has focussed primarily on the phosphoproteins pp60/56, which
      are Y-box proteins involved in a general packaging of mRNA. We now identify a
      third, abundant, integral component of stored mRNP particles, Xp54, which belongs
      to the family of DEAD-box RNA helicases. Xp54 was first detected by its ability
      to photocrosslink ATP. Subsequent sequence analysis identifies Xp54 as a member
      of a helicase subfamily which includes: human p54, encoded at a chromosomal
      breakpoint in the B-cell lymphoma cell line, RC-K8; Drosophila ME31B, encoded by
      a maternally-expressed gene, and Saccharomyces pombe Ste13, cloned by
      complementation of the sterility mutant ste13. Expression studies reveal that the
      gene encoding Xp54 is transcribed maximally at early oogenesis: no transcripts
      are detected in adult tissues, other than ovary. Using a monospecific antibody
      raised against native Xp54, its presence in mRNP particles is confirmed by
      immunoblotting fractions bound to oligo(dT)-cellulose and separated by rate
      sedimentation and buoyant density. On isolating Xp54 from mRNP particles, it is
      shown to possess an ATP-dependent RNA helicase activity. Possible functions of
      Xp54 are discussed in relation to the assembly and utilization of mRNP particles.

PMID- 9023106
TI  - Multi-organ characterization of mitochondrial genomic rearrangements in ad
      libitum and caloric restricted mice show striking somatic mitochondrial DNA
      rearrangements with age.
AB  - Mitochondrial DNA (mtDNA) rearrangements have been shown to accumulate with age
      in the post-mitotic tissues of a variety of animals and have been hypothesized to
      result in the age-related decline of mitochondrial bioenergetics leading to
      tissue and organ failure. Caloric restriction in rodents has been shown to extend
      life span supporting an association between bioenergetics and senescence. In the
      present study, we use full length mtDNA amplification by long-extension
      polymerase chain reaction (LX-PCR) to demonstrate that mice accumulate a wide
      variety of mtDNA rearrangements with age in post mitotic tissues. Similarly,
      using an alternative PCR strategy, we have found that 2-4 kb minicircles
      containing the origin of heavy-strand replication accumulate with age in heart
      but not brain. Analysis of mtDNA structure and conformation by Southern blots of
      unrestricted DNA resolved by field inversion gel electrophoresis have revealed
      that the brain mtDNAs of young animals contain the traditional linear, nicked,
      and supercoiled mtDNAs while old animals accumulate substantial levels of a
      slower migrating species we designate age-specific mtDNAs. In old caloric
      restricted animals, a wide variety of rearranged mtDNAs can be detected by LX-PCR
      in post mitotic tissues, but Southern blots of unrestricted DNA reveals a marked
      reduction in the levels of the age- specific mtDNA species. These observations
      confirm that mtDNA mutations accumulate with age in mice and suggest that caloric
      restriction impedes this progress.

PMID- 9023108
TI  - DNA binding and subunit interactions in the type I methyltransferase M.EcoR124I.
AB  - The type I DNA methyltransferase M.EcoR124I consists of two methylation subunits
      (HsdM) and one DNA recognition subunit (HsdS). When expressed independently, HsdS
      is insoluble, but this subunit can be obtained in soluble form as a GST fusion
      protein. We show that the HsdS subunit, even as a fusion protein, is unable to
      form a discrete complex with its DNA recognition sequence. When HsdM is added to
      the HsdS fusion protein, discrete complexes are formed but these are unable to
      methylate DNA. The two complexes formed correspond to species with one or two
      copies of the HsdM subunit, indicating that blocking the N-terminus of HsdS
      affects one of the HsdM binding sites. However, removal of the GST moiety from
      such complexes results in tight and specific DNA binding and restores full
      methylation activity. The results clearly demonstrate the importance of the HsdM
      subunit for DNA binding, in addition to its catalytic role in the
      methyltransferase reaction.

PMID- 9023107
TI  - Wild-type but not mutant p53 activates the hepatocyte growth factor/scatter
      factor promoter.
AB  - p53 transactivates the expression of a variety of genes by binding to specific
      DNA sequences within the promoter. We have investigated the ability of wild-type
      p53 and a non-DNA binding p53 mutant to activate the hepatocyte growth
      factor/scatter factor (HGF/SF) promoter using chloramphenicol acetyltransferase
      reporter constructs. We also used deletion sequences of the HGF/SF promoter to
      identify which regions, if any, were responsible for p53 binding. Our results
      show that wild-type but not mutant p53 activates the HGF/SF promoter when using 
      3000 and -755 bp upstream of the HGF/SF gene. This activation is lost when
      promoter sequences covering -365 and -239 bp are used. Analysis of the DNA
      sequence between -365 and -755 bp shows one putative p53 half-site with 80%
      homology to the consensus sequence and another half-site 3 bases downstream of
      this with 100% homology to the consensus sequence. In contrast to previously
      identified p53 binding DNA sequences, the downstream half-site is inverted. We
      propose that the HGF/SF promoter can be activated by wild-type p53 in vivo and
      that this could be as a result of a novel form of sequence-specific DNA binding.

PMID- 9023109
TI  - The p53 status of Chinese hamster V79 cells frequently used for studies on DNA
      damage and DNA repair.
AB  - Chinese hamster lung fibroblast V79 cells have been widely used in studies of DNA
      damage and DNA repair. Since the p53 gene is involved in normal responses to DNA
      damage, we have analyzed the molecular genetics and functional status of p53 in
      V79 cells and primary Chinese hamster embryonic fibroblast (CHEF) cells. The
      coding product of the p53 gene in CHEF cells was 76 and 75% homologous to human
      and mouse p53 respectively, and was 95% homologous to the Syrian hamster cells.
      The V79 p53 sequence contained two point mutations located within a presumed DNA
      binding domain, as compared with the CHEF cells. Additional immunocytochemical
      and molecular studies confirmed that the p53 protein in V79 cells was mutated and
      nonfunctional. Our results indicate that caution should be used in interpreting
      studies of DNA damage, DNA repair and apoptosis in V79 cells.

PMID- 9023110
TI  - The 5' terminal oligopyrimidine tract confers translational control on TOP mRNAs
      in a cell type- and sequence context-dependent manner.
AB  - TOP mRNAs are vertebrate transcripts which contain a 5'terminal oligopyrimidine
      tract (5'TOP), encode for ribosomal proteins and elongation factors 1alpha and 2,
      and are candidates for growth-dependent translational control mediated through
      their 5'TOP. In the present study we show that elongation factor 2 (EF2) mRNA is
      translationally regulated in a growth-dependent manner in cells of hematopoietic
      origin, but not in any of three different non-hematopoietic cell lines studied.
      Human beta1-tubulin mRNA is a new member of the family which contains all the
      hallmarks of a typical TOP mRNA, yet its translation is refractory to growth
      arrest of any of the examined cell lines. Transfection experiments indicate that
      the first 29 and 53 nucleotides of the mRNAs encoding EF2 and beta1-tubulin,
      respectively, contain all the translational cis-regulatory elements sufficient
      for ubiquitously conferring growth-dependent translational control on a reporter
      mRNA. These results suggest that the distinct translational regulation of TOP
      mRNAs reflects downstream sequences which can override the regulatory features of
      the 5'TOP in a cell type-specific manner. This notion is further supported by the
      fact that mutations within the region immediately downstream of the 5'TOP of
      rpS16 mRNA confer onto the resulting transcripts growth-dependent translational
      control with a cell type specificity similar to that displayed by EF2 mRNA.

PMID- 9023111
TI  - The fission yeast UVDR DNA repair pathway is inducible.
AB  - In addition to nucleotide excision repair (NER), the fission yeast
      Schizosaccharomyces pombe possesses a UV damage endonuclease (UVDE) for the
      excision of cyclobutane pyrimidine dimers and 6-4 pyrimidine pyrimidones. We have
      previously described UVDE as part of an alternative excision repair pathway,
      UVDR, for UV damage repair. The existence of two excision repair processes has
      long been postulated to exist in S.pombe, as NER-deficient mutants are still
      proficient in the excision of UV photoproducts. UVDE recognizes the
      phosphodiester bond immediately 5'of the UV photoproducts as the initiating event
      in this process. We show here that UVDE activity is inducible at both the level
      of uve1+ mRNA and UVDE enzyme activity. Further, we show that UVDE activity is
      regulated by the product of the rad12 gene.

PMID- 9023112
TI  - Mammalian cDNA and prokaryotic reporter sequences silence adjacent transgenes in
      transgenic mice.
AB  - The ovine beta-lactoglobulin gene is expressed efficiently and at high levels in
      the mammary gland of transgenic mice. In contrast, when this gene is linked to a
      second gene construct comprising a mammalian cDNA or a CAT reporter sequence it
      fails to be expressed in the majority of transgenic lines generated. We suggest
      that mammalian cDNAs and prokaryotic reporter sequences can serve as active foci
      for gene silencing in the mammalian genome.

PMID- 9023114
TI  - Influence of the nature of the porphyrin ligand on the nuclease activity of
      metalloporphyrin-oligonucleotide conjugates designed with cationic, hydrophobic
      or anionic metalloporphyrins.
AB  - The synthesis of metalloporphyrin-oligonucleotide conjugates with different
      metalloporphyrin moieties are described as well as the comparison of their in
      vitro nuclease efficiency toward a single-stranded DNA target. Between cationic,
      anionic and hydrophobic manganese porphyrins covalently linked to the
      oligonucleotide, the best nuclease activity was obtained with the cationic ones,
      suggesting that the affinity of the cleaver to the DNA target is a key factor.

PMID- 9023113
TI  - Rodent UV-sensitive mutant cell lines in complementation groups 6-10 have normal
      general excision repair activity.
AB  - Mammalian nucleotide excision repair is the primary enzymatic pathway for
      removing bulky lesions from DNA. The repair reaction involves three main steps:
      (i) dual incisions on both sides of the lesion; (ii) excision of the damaged base
      in an oligonucleotide 24-31 nt in length; (iii) filling in of the post-excision
      gap and ligation. We have developed assays that probe the individual steps of the
      reaction. Using these methods (assays for incision, excision and repair patch
      synthesis), we demonstrate that the mammalian excision nuclease system removes
      bulky lesions by incising mainly at the 22nd-25th phosphodiester bonds 5'and the
      3rd-5th phosphodiester bonds 3'of the lesion, thus releasing oligonucleotides
      primarily 26-29 nt in length. The resulting excision gap is filled in by DNA
      polymerases delta and epsilon as revealed by the 'phosphorothioate repair patch
      assay'. When these assays were employed with cell-free extracts from the
      moderately UV-sensitive rodent mutants in complementation groups 6-10, we found
      that these mutants are essentially normal in all three steps of the repair
      reaction. This leads us to conclude that these cell lines have normal in vitro
      repair activities and that the defects in these mutants are most likely in genes
      controlling cellular functions not directly involved in general excision repair.

PMID- 9023115
TI  - Characterization of multigene families in the micronuclear genome of Paramecium
      tetraurelia reveals a germline specific sequence in an intron of a centrin gene.
AB  - In Paramecium, as in other ciliates, the transcriptionally active macronucleus is
      derived from the germline micronucleus by programmed DNA rearrangements, which
      include the precise excision of thousands of germline-specific sequences
      (internal eliminated sequences, IESs). We report the characterization of
      micronuclear versions of genes encoding Paramecium secretory granule proteins
      (trichocyst matrix proteins, TMPs) and Paramecium centrins. TMP and centrin
      multigene families, previously studied in the macronuclear genome, consist of
      genes that are co-expressed to provide mixtures of related polypeptides that co
      assemble to form respectively the crystalline trichocyst matrix and the
      infraciliary lattice, a contractile cytoskeletal network. We present evidence
      that TMP and centrin genes identified in the macronucleus are also present in the
      micronucleus, ruling out the possibility that these novel multigene families are
      generated by somatic rearrangements during macronuclear development. No IESs were
      found in TMP genes, however, four IESs in or near germline centrin genes were
      characterized. The only intragenic IES is 75 bp in size, interrupts a 29 bp
      intron and is absent from at least one other closely related centrin gene. This
      is the first report of an IES in an intron in Paramecium.

PMID- 9023116
TI  - A high affinity binding site for the HIV-1 nucleocapsid protein.
AB  - The nucleocapsid protein (NC) of HIV-1 is a small zinc finger protein that
      contributes to multiple steps of the viral life cycle, including the proper
      encapsidation of HIV RNA. This is accomplished through an interaction between NC
      and a region at the 5'-end of the RNA, defined as the Psi element. However, the
      specificity of NC for Psi or for RNA in general is not well understood. To study
      this problem, we used SELEX to identify high affinity RNA ligands that bind to
      NC. A 'winner' molecule (SelPsi), as well as a subregion of Psi RNA, were further
      characterized to understand the interaction between NC and SelPsi and its
      relationship to the interaction between NC and Psi. The comparison makes
      predictions about the sequence and structure of a high affinity binding site
      within the HIV-1 Psi element.

PMID- 9023117
TI  - Basal transcription factors TBP and TFIIB and the viral coactivator E1A 13S bind
      with distinct affinities and kinetics to the transactivation domain of NF-kappaB
      p65.
AB  - Transactivation domains (TADs) are able to contact several components of the
      basal transcription apparatus and co-activator molecules. In order to study these
      interactions in biophysical detail, binding of the well-characterized TAD from
      the human transcription factor NF-kappaB p65 (RelA) to the basal transcription
      factors TBP and TFIIB and the viral co-activator protein E1A 13S was chosen as a
      model system to investigate the kinetics and affinities of such protein-protein
      interactions by surface plasmon resonance analysis. The TAD of NF-kappaB p65
      showed remarkably different affinities and kinetics in binding to the various
      proteins. The real-time kinetic measurements revealed an association rate
      constant (kass) of 2.3 x 10(6)/M/s for the interaction between the p65 TAD and
      TBP. The association rate constants of the p65 TAD were much weaker for TFIIB
      (6.8 x 10(4)/M/s) and for the E1A 13S protein (4.9 x 10(4)/M/s). The dissociation
      rate constants (kdiss) were determined to be 7.9 x 10(-4)/s for TBP, 1.6 x 10(
      3)/s for TFIIB and 1.3 x 10(-3)/s for the E1A protein. Accordingly, the
      calculated dissociation constants (Kd) differed between 3.4 x 10(-10)M for the
      strongly binding TBP protein and 2.3 x 10(-8)M and 2.6 x 10(-8)M for the weaker
      binding TFIIB and E1A 13S proteins respectively. Non-linear analysis of the
      appropriate part of the sensorgrams revealed monophasic association and
      dissociation kinetics for binding between the p65 TAD and all three interaction
      partners. The remarkable differences in protein affinities add another aspect to
      a more detailed understanding of formation of the transcription preinitiation
      complex. The co-transfection of TBP and E1A 13S stimulated NF-kappaB p65
      dependent gene expression, showing the biological significance of these
      interactions.

PMID- 9023118
TI  - Enzymatic activities involved in the DNA resynthesis step of nucleotide excision
      repair are firmly attached to chromatin.
AB  - In this study the role of nuclear architecture in nucleotide excision repair
      (NER) was investigated by gentle dismantling of the cell and probing the
      capability of chromatin to carry out repair in vitro. The rationale behind this
      approach is that compartmentalization of NER at nuclear structures would make the
      enzymatic activities refractory to extraction by buffers that solubilize cellular
      membranes. In order to obtain intact chromatin primary human fibroblasts were
      encapsulated in agarose microbeads and lysed in isotonic buffers containing the
      non-ionic detergent Triton X-100. Under these conditions the majority of cellular
      proteins diffuse out of the beads, but the remaining chromatin is able to
      replicate and to transcribe DNA in the presence of triphosphates and Mg2+. UV
      irradiation of confluent repair-proficient human fibroblasts prior to lysis
      stimulated the incorporation of deoxynucleotide triphosphates in Triton X-100
      isolated chromatin, even under stringent lysis conditions. In addition,
      experiments with UV-sensitive xeroderma pigmentosum (complementation groups A and
      C) and Cockayne's syndrome fibroblasts (complementation group A) revealed that
      this repair synthesis was due to global genome repair activity. Transcription
      coupled repair was only detectable in cells permeabilized by streptolysin O
      (SLO). Repair synthesis in Triton X-100-isolated chromatin amounted to 15% of the
      total repair synthesis as measured in SLO-permeabilized cells. To allow the
      detection of these activities in vitro, presynthesis complexes have to be formed
      in intact cells, indicating that chromatin from Triton X-100-lysed cells is
      unable to initiate NER in vitro. Our data indicate that the components involved
      in the resynthesis step of NER are tightly associated with chromatin. A
      substantial fraction of total proliferating cell nuclear antigen (PCNA), which is
      required for the resynthesis step in NER, has been reported to become Triton X
      100 non-extractable and tightly associated with nuclear structures after UV
      irradiation of cells. We propose that Triton X-100-resistant repair synthesis
      might be mediated by this chromatin-bound fraction of total PCNA.

PMID- 9023119
TI  - A new method for straightening DNA molecules for optical restriction mapping.
AB  - We have developed an improved method of straightening DNA molecules for use in
      optical restriction mapping. The DNA was straightened on 3
      aminopropyltriethoxysilane-coated glass slides using surface tension generated by
      a moving meniscus. In our method the meniscus motion was controlled mechanically,
      which provides advantages of speed and uniformity of the straightened molecules.
      Variation in the affinity of the silanized surfaces for DNA was compensated by
      precoating the slide with single-stranded non-target blocking DNA. A small amount
      of MgCl2 added to the DNA suspension increased the DNA-surface affinity and was
      necessary for efficient restriction enzyme digestion of the straightened surface
      bound DNA. By adjusting the amounts of blocking DNA and MgCl2, we prepared slides
      that contained many straight parallel DNA molecules. Straightened lambda phage
      DNA (48 kb) bound to a slide surface was digested by EcoRI restriction
      endonuclease, and the resulting restriction fragments were imaged by fluorescence
      microscopy using a CCD camera. The observed fragment lengths showed excellent
      agreement with their predicted lengths.

PMID- 9023121
TI  - A novel tetracycline-dependent expression vector with low basal expression and
      potent regulatory properties in various mammalian cell lines.
AB  - The tetracycline-dependent expression system has gained increasing popularity for
      the expression of any gene of interest. Careful choice of the expression vector
      has been suggested to exploit the full potential of this system. A novel
      tetracycline-sensitive expression vector based on a modified mouse mammary tumor
      virus promoter achieved considerably improved regulatory properties in a series
      of cell lines tested under transient and stable conditions. Therefore, the
      applicability of the tetracycline-dependent expression system can be largely
      enhanced by careful adaptation of the expression vector to the host cell line.

PMID- 9023120
TI  - Intronic and exonic sequences modulate 5' splice site selection in plant nuclei.
AB  - Pre-mRNA transcripts in a variety of organisms, including plants, Drosophila and
      Caenorhabditis elegans, contain introns which are significantly richer in
      adenosine and uridine residues than their flanking exons. Previous analyses using
      exonic and intronic replacements between two nonequivalent 5'splice sites in the
      469 nt long rbcS3A intron 1 provided the first evidence indicating that, in both
      tobacco and Drosophila nuclei, 5'splice site selection is strongly influenced by
      the position of that site relative to the AU transition point between exon and
      intron. To differentiate between two potential models for 5'splice site
      recognition, we have expressed a completely different set of intronic and exonic
      replacement constructs containing identical 5'splice sites upstream of beta
      conglycinin intron 4 (115 nt). Mutagenesis and deletion of the upstream 5'splice
      site demonstrate that intronic AU-rich sequences function by promoting
      recognition of the most upstream 5'splice site rather than by masking the
      downstream 5'splice site. Sequence insertions define a role for AG-rich exonic
      sequences in plant pre-mRNA splicing by demonstrating that an AG-rich element is
      capable of promoting downstream 5'splice site recognition. We conclude that AU
      rich intronic sequences, AG-rich exonic sequences and the 5'splice site itself
      collectively define 5'intron boundaries in dicot nuclei.

PMID- 9023122
TI  - PCR-mediated direct gene disruption in Schizosaccharomyces pombe.
AB  - We have examined the feasibility and efficiency of PCR-mediated direct gene
      disruptions in the fission yeast Schizosaccharomyces pombe. In the present study,
      the S.pombe ura4+ gene was amplified by PCR with oligonucleotides that had short
      flanking regions ( approximately 40 bp) to the target gene. Using this purified
      PCR product we were able to disrupt genes in an S. pombe strain bearing aura4
      deletion, with an efficiency ranging between 1 and 3% among selected
      transformants. The results indicated that despite S.pombe's preference for non
      homologous or illegitimate recombination, even very short stretches of homologous
      regions could be used to target genes at a defined frequency in this organism.
      The successful disruption of four independent genes (sts1+, gcs1+, gsh2+and
      hmt1+) by this method further demonstrates that, despite the relatively low
      efficiency, the method is very feasible, and it's simplicity, especially when
      coupled to phenotype-based screening, should greatly facilitate disruption of
      genes in S.pombe.

PMID- 9023123
TI  - Transcriptional modulation of viral reporter gene constructs following induction
      of the cellular stress response.
AB  - In this study, we report that commonly used methods of transient transfection
      induce the cellular stress response and a recovery period is required following
      transfection when analyzing cellular stress responsive genes. Four transfection
      methods were examined for their ability to induce the stress response by
      measuring the expression of heat shock protein (hsp) 72. We demonstrate that
      electroporation increases expression of hsp 72 in HUT 78 cells. Additionally,
      DEAE-dextran and liposome-mediated transfection resulted in increased hsp 72
      expression in an adherent cell line (HeLa). Liposome-mediated transfection
      differentially induced cell stress, dependent on the transfection time in serum
      free culture conditions. The stress responsiveness of two viral promoters, the
      HTLV-1 long terminal repeat and CMV immediate early transcriptional unit were
      examined. We found the maximal stress-mediated enhancement of transcription with
      both promoters did not occur until the cells recovered for 24 h following
      transfection.

PMID- 9023124
TI  - A simple and rapid method for isolation of high quality genomic DNA from fruit
      trees and conifers using PVP.
AB  - Because DNA degradation is mediated by secondary plant products such as phenolic
      terpenoids, the isolation of high quality DNA from plants containing a high
      content of polyphenolics has been a difficult problem. We demonstrate an easy
      extraction process by modifying several existing ones. Using this process we have
      found it possible to isolate DNAs from four fruit trees, grape (Vitis spp.),
      apple (Malus spp.), pear (Pyrus spp.) and persimmon (Diospyros spp.) and four
      species of conifer, Pinus densiflora, Pinus koraiensis,Taxus cuspidata and
      Juniperus chinensis within a few hours. Compared with the existing method, we
      have isolated high quality intact DNAs (260/280 = 1.8-2.0) routinely yielding 250
      500 ng/microl (total 7.5-15 microg DNA from four to five tissue discs).

PMID- 9023125
TI  - Cardiac enzyme availability and hospital length of stay.

PMID- 9023126
TI  - Optical tweezers and immunoassay.

PMID- 9023127
TI  - Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency.
AB  - Pharmacogenetics is the study of the linkage between an individual's genotype and
      that individual's ability to metabolize a foreign compound. Differences in
      metabolism of therapeutics can lead to severe toxicity or therapeutic failure by
      altering the relation between dose and blood concentration of the
      pharmacologically active drug. Phenotypes exhibiting poor and ultraextensive
      metabolism result from genetic variance (polymorphism) of enzymes involved in
      metabolism. Thus, in pharmacogenetic studies one applies genotyping of
      polymorphic alleles encoding drug-metabolizing enzymes to the identification of
      an individual's drug metabolism phenotype. This knowledge, when applied to dosing
      or drug selection, can avoid adverse reactions or therapeutic failure and thus
      enhance therapeutic efficiency. More than 25 commonly prescribed medicines are
      metabolized by the cytochrome P-4502D6 (CYP2D6) isoenzyme, and polymorphism of
      the CYP2D6 gene affects the therapeutic management of up to 17% of individuals in
      some ethnic groups. In this review, we summarize and update information
      concerning drug-metabolizing genotypes with emphasis on CYP2D6 genotyping
      techniques that can be applied by the clinical laboratory for linking human
      genetics to therapeutic management.

PMID- 9023128
TI  - C677T mutation of methylenetetrahydrofolate reductase gene determined in blood or
      plasma by multiple-injection capillary electrophoresis and laser-induced
      fluorescence detection.
AB  - We constructed an assay to detect the common C677T mutation in the
      methylenetetrahydrofolate reductase gene. The mutation creates a Hinfl
      recognition site detected by restriction cleavage of a 198-bp fragment amplified
      in the polymerase chain reaction (PCR). Digested samples were subjected to
      capillary electrophoresis with laser-induced fluorescence detection (CE-LIF),
      with hydroxypropylmethylcellulose as the sieving matrix and SYBR Green I as the
      fluorescent dye. After amplification but before digestion, we added to the PCR
      mixture a fragment with the HinfI recognition site and a 15-bp truncation at the
      3' end. Using this procedure, we could (a) verify completeness of digestion and
      monitor injection, (b) assign genotypes on the basis of pattern recognition, and
      (c) develop a multiple-injection mode with simultaneous separation of as many as
      eight samples. A seminested PCR protocol in combination with CE-LIF allowed
      genotyping of plasma/serum samples 20 years old.

PMID- 9023129
TI  - Stability of long-chain and short-chain 3-hydroxyacyl-CoA dehydrogenase activity
      in postmortem liver.
AB  - Inherited enzyme defects in mitochondrial fatty acid oxidation (FAO) are
      associated with acute metabolic crisis and sudden death. Necropsy findings may be
      subtle, yielding no diagnosis and precluding genetic counseling. Preliminary
      identification of an FAO disorder requires the use of sophisticated tools (e.g.,
      GC/MS) and specific body fluids, and the diagnosis rests on molecular analysis or
      enzyme assay. At present, confirmation of long-chain or short-chain 3-hydroxyacyl
      CoA dehydrogenase deficiency relies on measurement of enzyme activity. Here, we
      report our examination of the effect of storage temperature (25, 4, -20, and -70
      degrees C) and the postmortem interval on enzyme activities in rat and human
      liver. Enzyme activity decreases 50% in 30 h in samples stored at 25 degrees C,
      whereas 55 h at 4 degrees C is required to reach this value; freezing minimizes
      this loss. Regardless of rate of degradation, however, the short-chain to long
      chain activity ratio remains constant--which should make it possible to
      differentiate postmortem degradation from enzyme deficiency.

PMID- 9023130
TI  - Human prostate-specific glandular kallikrein is expressed as an active and an
      inactive protein.
AB  - A polymorphism in the human prostate-specific glandular kallikrein (hKLK2) gene
      was described by direct sequencing (by PCR) of genomic DNAs isolated from
      prostatic cancer tissue, benign prostatic hyperplasia tissue, and blood leukocyte
      specimens. Results showed two forms of human prostate-specific glandular
      kallikrein protein (hK2), a consequence of a change from C to T at base 792 in
      the hK2 coding region. Producing the two forms as recombinant proteins in insect
      cells demonstrated that Arg226-hK2 (CC genotype) is an active protein and Trp226
      hK2 (TT genotype) is inactive. Polymorphism studies of 36 patients with prostatic
      diseases identified only 1 with the TT genotype. The same kind of polymorphism
      was not detected in the human prostate-specific antigen (hKLK3) gene. Arg226-hK2
      possessed only trypsin-like enzyme activity, whereas recombinant human prostate
      specific antigen (hPSA) had only chymotrypsin-like activity. Monoclonal and
      polyclonal antibodies raised against hPSA purified from seminal plasma detected
      both active and inactive hK2. Thus, because inactive as well as stable hK2
      protein may be present, a lack of trypsin-like activity in hPSA standards is not
      enough to confirm that the materials are free of hK2 contamination.

PMID- 9023132
TI  - Passage of silver ions through membrane-mimetic materials, and its relevance to
      treatment of burn wounds with silver sulfadiazine cream.
AB  - Treatment of acute burn wounds with silver sulfadiazine has raised concern of
      potential silver toxicity. As the wound heals, a barrier forms between the silver
      sulfadiazine and the blood, but this membrane is not impenetrable, and so silver
      absorption is still possible. In this work, we have modeled chemical systems to
      investigate the transport of silver sulfadiazine and silver chloride through
      cellulose, chitosan, collagen, and polyethylene membranes into the following
      media: synthetic serum electrolyte solution (SSES), SSES plus glutathione, and
      human serum, to simulate some of the chemical processes occurring at a burn wound
      during healing. Our results clearly indicate that membranes can retard the
      movement of silver ions, especially those that have silver-binding properties.
      This suggests that silver absorption at a healing wound will be minimized by
      entrapment of silver in the growing membrane network, and thus the likelihood of
      silver toxicity will be reduced.

PMID- 9023131
TI  - Plasma and erythrocyte vitamin E content in asymptomatic hypercholesterolemic
      subjects.
AB  - The present study was designed to assess plasma and erythrocyte vitamin E
      concentrations in 57 asymptomatic hypercholesterolemic (HC) men compared with 56
      normocholesterolemic (NC) men. Vitamin E concentrations were determined by using
      a reversed-phase HPLC method. Compared with NC subjects, HC men had a
      significantly lower red blood cell (RBC) vitamin E content in spite of their
      normal plasma vitamin E concentration. This study demonstrates that total plasma
      vitamin E concentration is not a suitable predictor of cell vitamin E status and
      suggests an abnormal transfer of tocopherol between plasma and RBCs in HC men.
      Moreover, the RBCs of HC men were more susceptible to a peroxidative stress. The
      strong correlation between RBC susceptibility to oxidation and RBC vitamin E
      content suggests that the low RBC vitamin E content found in HC men has
      physiological consequences on the RBC oxidation.

PMID- 9023133
TI  - Screening children exposed to lead: an assessment of the capillary blood lead
      fingerstick test.
AB  - We describe results of a 3-year study in which 499 paired venous and capillary
      blood specimens, collected by fingerstick on the same day, were analyzed for lead
      (BPb) and erythrocyte protoporphyrin (EP). False-positive rates (FPRs) and the
      proportion of false positives were calculated at four BPb thresholds. At the 100
      microg/L threshold, the FPR for all data was 13%, but the proportion of false
      positives was only 5%. The log ratios of capillary-to-venous BPb data indicate
      that, with the exception of eight outliers, two subpopulations exist that follow
      a log-normal distribution. These two subpopulations, the "core" (n = 303) and
      "shifted" (n = 188) groups, on average generated a positive bias at 100 microg/L
      BPb of 8.6% and 30.3%, respectively. The log ratios of capillary-to-venous EP
      data followed a normal distribution, indicating that capillary EP is not
      statistically different from venous EP.

PMID- 9023134
TI  - Uniform solid-phase extraction procedure for toxicological drug screening in
      serum and urine by HPLC with photodiode-array detection.
AB  - In this HPLC-diode-array detection method for toxicological drug screening, a
      mixed-mode solid-phase extraction procedure is optimized for isolation of a broad
      range of drugs from serum and urine. Basic, neutral, and weakly acidic drugs are
      uniformly recovered. The extract from the solid-phase cartridge is readily
      injected to a reversed-phase HPLC column for separation by gradient elution.
      Unknown drugs and metabolites in urine and serum samples from acute drug
      poisoning cases are rapidly identified by matching their retention times and
      ultraviolet spectra with hundreds of reference compounds in the library. Urine
      metabolites of common toxicants from various medications and drugs of abuse are
      recorded, with their changes of retention times and ultraviolet spectra as
      related to their metabolic transformations. Glucuronide conjugates of common
      benzodiazepines, tricyclic antidepressants, and beta-blockers are examined
      directly without chemical or enzymatic hydrolysis. The system is reliable for
      diverse clinical investigations of drug overdoses, drug-induced psychoses, and
      substance abuse.

PMID- 9023135
TI  - Impact of CK-MB testing policies on hospital length of stay and laboratory costs
      for patients with myocardial infarction or chest pain.
AB  - We obtained data on hospital length of stay (LOS) and total laboratory charges
      for Medicare patients admitted to 82 hospitals in Massachusetts during 1994. Five
      Diagnosis Related Groups (DRGs) were selected: surviving acute myocardial
      infarction (AMI) with, and without, complications; AMI with death; angina
      pectoris; and chest pain. The hospitals were grouped according to their
      laboratory policies for testing CK-MB (e.g., frequency of assay runs; information
      obtained by telephone survey). The study was conducted to determine whether there
      was an association between turnaround times for results and LOS for cardiac DRGs.
      The mean LOS for AMIs with complication for 1513 patients admitted to 22
      hospitals whose laboratories perform CK-MB testing once or twice daily was 8.4
      days [95% confidence interval (CI): 8.2-8.7]. In contrast, the mean LOS for
      hospitals with CK-MB test policies of at least 3 runs daily or random-access stat
      was significantly (P <0.05) lower, 7.7 days (CI: 7.4-8.0 and 7.5-7.9,
      respectively). Overall laboratory charges were lower in the hospitals with
      shorter LOS. With one exception, there was no significant difference in LOS
      between patients with DRGs of angina pectoris or chest pain or other AMI DRGs.
      For AMI, a CK-MB testing policy that produces shorter turnaround times may be
      justified because of an association with reductions in LOS and overall laboratory
      costs.

PMID- 9023136
TI  - Medians for second-trimester maternal serum alpha-fetoprotein, human chorionic
      gonadotropin, and unconjugated estriol; differences between races or ethnic
      groups.
AB  - Second-trimester maternal serum alpha-fetoprotein (AFP), human chorionic
      gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in
      screening fetuses at high risk for Down syndrome or open neural tube defects
      (ONTD). For test interpretation, individual patient values of these three
      analytes are related to population-derived median values. We evaluated data from
      >21000 pregnancies to determine the extent of race-specific differences in median
      concentrations. For samples at most gestational ages, median AFP, hCG, and uE3
      values for white, black, Hispanic, and other patients were all significantly
      different. Differences remained significant even when data were corrected for
      patient weights. For each analyte, the extent of the variation was not the same
      at different gestational ages. Differences in median values across race/ethnicity
      groups appear to have only a small impact in Down syndrome screening but it may
      be appropriate to use alternative sets of AFP medians or adjustment factors to
      AFP medians for some Asian populations receiving ONTD screening.

PMID- 9023137
TI  - Critical difference between serial measurements of CK-MB mass to detect
      myocardial damage.
AB  - To assess the critical difference in serial measurements of CK-MBmass and the
      ability of this critical difference to detect myocardial damage, we studied 110
      patients in whom an acute myocardial infarction (AMI) had been ruled out. Blood
      samples were drawn at 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 h after onset of
      symptoms. With a critical difference of 72.6%, an increase of >2.0 microg/L
      between two CK-MBmass measurements was determined to be significant. Twenty-three
      of the non-AMI patients had an increase in CK-MBmass >2.0 microg/L, but five of
      these did not have an abnormal concentration of troponin T (i.e., not >0.1
      microg/L). Also among the 110 non-AMI patients, 22 did have an abnormal troponin
      T value, 18 of whom (82%) also had CK-MBmass increased by >2.0 microg/L. In 20 of
      the 23 patients with an increase in CK-MBmass >2.0 microg/L, this increase was
      detected from the values for two samples collected at 5 and 12 h after onset of
      symptoms. In conclusion, using the critical difference for CK-MBmass defined as
      an increase >2.0 microg/L detected myocardial damage in patients without AMI.

PMID- 9023138
TI  - Increased serum concentration of carbohydrate-deficient transferrin in patients
      with combined pancreas and kidney transplantation.
AB  - Serum concentration of carbohydrate-deficient transferrin (cCDT) is used for
      laboratory diagnosis and follow-up of chronic alcohol abuse. In analyzing by
      CDTect-RIA (Pharmacia) sera from outpatients with combined pancreas and kidney
      transplantation and no excessive alcohol consumption, we found above-normal
      values for cCDT and CDT/transferrin ratios (CDT/Tf) in more than half of the
      samples. Isoelectric focusing of these samples showed distinct bands of
      carbohydrate-deficient isotransferrins, supporting the abnormal findings from the
      CDTect assay. In contrast, diabetics and outpatients who had received only kidney
      transplants showed normal values for cCDT, CDT/Tf, and isotransferrin patterns.
      Increased serum Tf, sialidase-producing microorganisms, and immunosuppressive
      medication were eliminated as causes of these abnormal cCDT and CDT/Tf results.
      Successful pancreas transplantation leads to hyperinsulinemia and normoglycemia,
      in contrast to hypoinsulinemia and hyperglycemia in the patients who receive
      kidney transplants alone. These factors may have pathogenic importance for CDT
      increase, yielding results falsely interpreted as positive with respect to
      alcohol abuse in patients with combined pancreas and kidney transplantation.

PMID- 9023139
TI  - Two-dimensional gel electrophoresis detects prostate-specific antigen-alpha1
      antichymotrypsin complex in serum but not in prostatic fluid.
AB  - We investigated the interaction between prostate-specific antigen (PSA) and 1
      antichymotrypsin (ACT) in prostatic secretions, identifying PSA and ACT in human
      serum, prostatic fluid, and seminal plasma by two-dimensional gel electrophoresis
      (2-D PAGE). Both PSA and ACT were detected in all three body fluids, but PSA-ACT
      complex was detected only in serum. Moreover, the 2-D PAGE Western blot staining
      profile for ACT from serum differed from that for prostatic fluid or seminal
      plasma. Incubation of prostatic fluid with purified ACT led to formation of PSA
      ACT complex. Incubation of prostatic fluid with purified PSA, however, failed to
      form the complex, suggesting that the ACT in prostatic fluid was inactive or
      inhibited. Given that physiological concentrations of zinc inhibited the
      formation of PSA-ACT complex, we consider zinc a possible physiological inhibitor
      of the formation of the PSA-ACT complex. These results indicate that the failure
      to detect the PSA-ACT complex in prostatic fluid could be related to the
      inactivation of ACT, the presence of inhibitors (e.g., zinc), or simply the
      PSA:ACT ratio in the fluid.

PMID- 9023140
TI  - Clinical evaluation of serial blood processing at point of care.
AB  - The Axial Separation Module (ASM), which separates whole-blood specimens serially
      in Axial Process Containers (APC), was evaluated for clinical performance at the
      University of Virginia Health Sciences Center (UVA HSC) in a community-based
      outpatient laboratory (North Ridge Clinic). We hypothesized that moving the task
      of blood separation to point of care would reduce specimen turnaround time within
      the main laboratory. Blood drawn into an APC was separated in the ASM at point of
      care at the North Ridge Clinic. Blood drawn into a Vacutainer Tube was separated
      in a conventional centrifuge at the main laboratory. Turnaround time was
      calculated for the "chem 17" test from files stored in our laboratory information
      system. Blood serially separated at point of care yielded turnaround time savings
      for specimens originating from the North Ridge Clinic. Average turnaround time
      decreased by 24%. Phlebotomists found no appreciable workload increase from
      incorporating the ASM as a point-of-care blood separation device. Phlebotomists
      also found that they could immediately detect hemolysis. We concluded that serial
      separation at point of care reduces specimen turnaround time at the main
      laboratory. The ASM/APC was found to be better suited for point-of-care blood
      separation than a conventional centrifuge. We speculate that immediate blood
      separation has the potential to improve the quality of analytical results.

PMID- 9023141
TI  - Competitive enzyme immunoassay with monoclonal antibody for homovanillic acid
      measurement in human urine samples.
AB  - A fast competitive enzyme immunoassay (EIA) for measuring homovanillic acid in
      human urine samples was developed with a monoclonal antibody and
      acetylcholinesterase as enzyme label. Enzyme detection was performed by an easy
      colorimetric assay. Monoclonal antibodies were screened on the basis of
      sensitivity, specificity, and correlation studies. EIA has a detection limit of
      0.5 micromol/L, a CV <10% in the 1.25-10 micromol/L range, and intra- and
      interassay CVs of <10%. Cross-reactivity with vanillylmandelic acid was 0.5% and
      <8% for other structurally related catecholamine metabolites. Parallelism of the
      EIA was shown in dilution studies and the correlation with routine HPLC assay in
      62 normal and pathologic samples was EIA = 1.492 (HPLC) - 3.46, S(y/x), = 47.52,
      range = 4-1800 micromol/L, r2 = 0.977. Additional data concerning the validity of
      this assay were provided by HPLC analysis of urinary immunoreactive material.

PMID- 9023142
TI  - Fluid elements--a concept for automation of diagnostic tests.
AB  - Constructs consisting of a channel, a membrane, and an absorber are designed for
      autonomously carrying out various liquid-handling functions of analytical tests.
      These so-called fluid elements can be used to set up various circuits for
      conducting several kinds of analytical tests. To demonstrate the feasibility of
      this concept, we constructed such a circuit and used it to perform, with two
      handling steps, an ELISA of hepatitis B surface antigen. The detection limit of
      the assay was comparable with those of state-of-the-art ELISAs for screening
      blood, and results could be obtained within a total test time of 20 min. We
      anticipate that this concept of automation may also serve as a basis for new,
      highly simplified immunoanalyzers.

PMID- 9023143
TI  - Optical tweezers-based immunosensor detects femtomolar concentrations of
      antigens.
AB  - We used optical tweezers (optical trapping technology) to measure the force
      required to separate antigen-antibody bonds. Under competitive-binding
      conditions, we used the force determination to detect and measure protein antigen
      concentrations as small as 1 fmol/L (10(-15) mol/L).

PMID- 9023144
TI  - Whole-blood test for total cholesterol by a self-metering, self-timing disposable
      device with built-in quality control.
AB  - A whole-blood test for total cholesterol has been developed that is performed in
      a low-cost disposable flow device without user intervention (after sample
      addition). The device meters the sample, separates plasma from erythrocytes, and
      precisely times plasma flow into various reagent compartments, including a
      quality-assurance chamber. Test results are displayed as a well-defined and
      easily readable color bar. A quality-control window attests to the integrity of
      the test components. Here, we describe the assembly and individual functions of
      the device and report its performance characteristics. Precision and accuracy
      studies in four clinical studies at independent locations yielded total
      imprecision of <5% and an average bias of 1.35% vs the Abell-Kendall method.

PMID- 9023145
TI  - Comparison of methods for measurement of apolipoprotein B and cholesterol in low
      density lipoproteins.
AB  - We describe a new method for the direct measurement of LDL-apolipoprotein (apo) B
      by using a commercial kit that isolates LDL by immunoseparation. We evaluated
      immunoseparation of LDL for apo B and cholesterol measurement in 46 dyslipidemic
      patients with LDL-cholesterol (LDL-C) between 1.5 and 8.2 mmol/L, 11 of whom had
      plasma triglyceride (TG) concentrations >4.0 mmol/L. There was a reasonable
      correlation (r = 0.94, n = 40) between LDL-apo B obtained after immunoseparation
      and d >1.006 kg/L apo B obtained after ultracentrifugation. LDL-C by the
      immunoseparation method also correlated well (r = 0.98, n = 46) with the d >1.006
      kg/L cholesterol after ultracentrifugation. These results show that
      immunoseparation can be used to determine LDL-apo B, even in hypertriglyceridemic
      samples. This method may provide a quick and simple alternative for the
      identification of hyperapobetalipoproteinemia, even when TG concentrations are
      high.

PMID- 9023146
TI  - Serum ionized magnesium in chronic alcoholism: is it really decreased?
AB  - Chronic alcoholism is associated with a marked deficit in total magnesium (tMg).
      However, little is known about the status of the physiologically active form,
      ionized magnesium (iMg). We assessed serum iMg (measured with two ion-selective
      electrodes, AVL 988-4 and NOVA CRT) and tMg concentrations in chronic alcoholics
      at admission (n = 31) and after abstinence (n = 13) and compared these results
      with those for a control group (n = 40). At admission, the tMg and NOVA iMg
      concentrations in alcoholics (0.78 +/- 0.020 and 0.38 +/- 0.016 mmol/L,
      respectively) were significantly less (P <0.001) than in the controls (0.85 +/-
      0.008 and 0.50 +/- 0.006 mmol/L). The AVL iMg results, however, did not differ
      significantly between the two groups: 0.53 +/- 0.013 vs 0.56 +/- 0.006 mmol/L,
      respectively (P >0.05). The mean iMg between the two analyzers differed
      significantly in both groups (P <0.001). After 3 weeks of abstinence, the
      alcoholics showed a significant increase in tMg (P <0.001) and in both NOVA and
      AVL iMg values (P <0.01 for each). tMg concentrations were positively correlated
      with the AVL iMg values in both alcoholics and controls but correlated positively
      with the NOVA iMg results only in the controls. Thus, the altered status of iMg
      is instrument-dependent, and the usefulness of the measurement in alcoholics is
      yet to be determined.

PMID- 9023147
TI  - Automated selection of statistical quality-control procedures to assure meeting
      clinical or analytical quality requirements.

PMID- 9023148
TI  - Rapid screening for alpha1-antitrypsin Z and S mutations.

PMID- 9023149
TI  - Quantitative immunological detection of total estrogen receptor (cytosolic and
      nuclear) in term decidua of preeclampsia: a preliminary study.

PMID- 9023150
TI  - Speciation of arsenic in serum, urine, and dialysate of patients on continuous
      ambulatory peritoneal dialysis.

PMID- 9023152
TI  - Preparing for Critical Care Analyses in the 21st Century, 16th international
      symposium.

PMID- 9023151
TI  - Lipemia interference with a rate-blanked creatinine method.

PMID- 9023153
TI  - Cardiac troponins T and I before and after renal transplantation.

PMID- 9023154
TI  - Profound hypercalcemia in continuous veno-venous hemofiltration dialysis with
      trisodium citrate anticoagulation and hepatic failure.

PMID- 9023155
TI  - Thyroglobulin IRMA Pasteur immunoassay: sensitivity of the assay and interference
      from thyroglobulin autoantibodies.

PMID- 9023156
TI  - Apparent positive interference from an etoposide metabolite, but not etoposide,
      in measuring urinary vanillylmandelic acid.

PMID- 9023157
TI  - Serum cardiac troponin I, creatine kinase (CK), and CK-MB in early posttraumatic
      rhabdomyolysis.

PMID- 9023158
TI  - Age and referral to coronary angiography after an abnormal treadmill thallium
      test.
AB  - This study investigated the association between age and referral to coronary
      angiography among ambulatory adults with an abnormal treadmill thallium scan. The
      subjects studied were 416 consecutive adults who were > or = 30 years old, under
      the care of cardiologists, and had an abnormal treadmill thallium scan between
      1990 and 1993 at the Cleveland Clinic Foundation. The primary end point was
      performance of coronary angiography within 90 days of the treadmill test.
      Coronary angiography was performed in 163 subjects. Coronary angiography was
      performed in 46% of patients aged 30-49 years, in 53% of those aged 50 to 64
      years, in 33% of those aged 65 to 74 years, and in only 18% of those aged > or =
      75 years (chi2 test for trend, p < 0.0001). After adjustment for potential
      confounders, age remained associated with a lower rate of referral to angiography
      (p < 0.0001). During 2 years of follow-up 34 deaths occurred (14 cardiac), with
      particularly high mortality rates among those aged >74 years (cumulative rate
      31%, 95% confidence interval 16% to 47%). The number of abnormal thallium scan
      segments was predictive of death (p = 0.02). These data suggest that increasing
      age is associated with a lower rate of referral to coronary angiography after an
      abnormal treadmill thallium test.

PMID- 9023159
TI  - Higher prevalence and greater severity of coronary disease in short versus tall
      men referred for coronary arteriography.
AB  - The incidence of myocardial infarction is higher in short individuals than in
      tall ones. To test whether the prevalence and severity of coronary disease is
      greater in short than in tall individuals, we compared a group of short men
      (height < [mean height - one SD]) to a group of tall men (height > [mean height +
      one SD]) drawn from a sample of 1046 consecutive men referred for coronary
      arteriography. Short men had a higher frequency of > or = 50% diameter stenosis;
      more diseased vessels (1.61 +/- 1.09 vs 1.15 +/- 1.11, p = 0.0004); a higher
      frequency of three-vessel disease (26.8% vs 16.1%, p = 0.04); and more total
      occlusions (40.1% vs 27.3%, p = 0.03). By multivariate analysis, height
      independently predicted > or = 50% lesions in the right coronary artery (p =
      0.01) and left anterior descending artery (p = 0.06); three-vessel disease (p =
      0.04); total occlusion (p = 0.04); and the number of diseased vessels (p =
      0.005). This higher prevalence and greater severity of coronary disease may
      explain the higher incidence of and deaths caused by myocardial infarction
      previously reported in short men.

PMID- 9023160
TI  - Dependency of premature ventricular contractions on heart rate.
AB  - To identify a method for characterizing the dynamic behavior of ventricular
      arrhythmias at different heart rates, 201 consecutive patients with frequent
      premature ventricular contractions (PVCs) underwent two 24-hour
      electrocardiographic monitoring periods. The percentage of PVCs for each cycle
      length was calculated and then analyzed by linear regression analysis. On the
      basis of the significance of the p value, and the positive or negative value of
      the slope, we identified three trends: a tachycardia-enhanced pattern (p < 0.01,
      slope negative), a bradycardia-enhanced pattern (p < 0.01, slope positive), and
      an indifferent pattern (p > 0.01). During the first monitoring period, a
      tachycardia-enhanced pattern was present in 56 patients (28%), a bradycardia
      enhanced pattern was present in 49 patients (24%), and an indifferent pattern was
      present in 96 patients (48%). This relationship was reproducible in 41 of the
      patients with a tachycardia-enhanced pattern (73%), in 29 of the patients with a
      bradycardia-enhanced pattern (59%), and in 70 patients with an indifferent
      pattern (72%). In conclusion, it is possible to identify a spontaneous trend
      between the incidence of ventricular arrhythmias and the length of the preceding
      cardiac cycle that seems to remain stable over time.

PMID- 9023161
TI  - Exaggerated blood pressure response to exercise in children with increased low
      density lipoprotein cholesterol.
AB  - Arterial vascular responses are characteristically altered with
      hypercholesterolemia: conduit vessels manifest increased stiffness, and conduit
      and resistance vessels demonstrate impaired endothelium-dependent dilation and
      augmented vasoconstriction to neurohumoral stimulation. These changes should be
      reflected in an exaggerated blood pressure increase in response to exercise. To
      evaluate this hypothesis, we compared the blood pressure response to treadmill
      exercise in children with hypercholesterolemia and children with normal lipid
      levels. In a preliminary retrospective study, 15 hypercholesterolemic boys 10 to
      18 years old underwent treadmill exercise testing, and their blood pressure
      results were compared with those of 32 normolipidemic children in the same age
      group who had undergone treadmill exercise electively in the same time period. In
      the second phase, 10 hypercholesterolemic boys and 10 normolipidemic age-matched
      boys were evaluated prospectively according to the same protocol. Treadmill
      exercise involved a modified Bruce protocol with heart rate and blood pressure
      measured before exercise, immediately after exercise, and throughout recovery.
      Office blood pressures were normal in all children, with no significant
      difference between groups. With treadmill exercise, all subjects achieved >95% of
      predicted maximum heart rate and endurance times, maximum oxygen consumption, and
      maximum respiratory ratio did not differ between groups. Results of the
      retrospective and prospective groups were similar and were therefore combined.
      Children with increased low-density lipoprotein (LDL) cholesterol had
      significantly higher systolic and diastolic blood pressures immediately before
      treadmill exercise (systolic 120 +/- 13 mm Hg vs 113 +/- 13 mm Hg, p < 0.03;
      diastolic 68 +/- 8 mm Hg vs 63 +/- 9 mm Hg, p < 0.01). After exercise, blood
      pressures were again significantly higher in the subjects with high LDL
      cholesterol (systolic 182 +/- 20 mm Hg vs 160 +/- 23 mm Hg, p < 0.0003; diastolic
      77 +/- 12 mm Hg vs 72 +/- 9 mm Hg, p < 0.03). At the end of recovery, systolic
      blood pressures remained significantly higher in subjects with high LDL
      cholesterol (120 +/- 9 mm Hg vs 112 +/- 12 mm Hg, p < 0.005). In this study,
      children with severely increased LDL cholesterol had an exaggerated blood
      pressure response to exercise when compared with normolipidemic control subjects.
      The study findings suggest that control of arterial vascular tone may already be
      altered in children with hypercholesterolemia.

PMID- 9023162
TI  - Cardiovascular responses to dynamic submaximal exercise in children previously
      treated with anthracycline.
AB  - This study assessed the long-term (5-year) outcome of pediatric low-dose
      anthracycline therapy on the circulatory response to moderate exercise. Thirteen
      patients (13 +/- 4 years old) and 15 age-matched control subjects completed a
      maximal cycle ergometer protocol as well as two 5-minute cycling tests at 33% and
      66% maximal oxygen uptake (V(O2)max) for determination of cardiac index (carbon
      dioxide rebreathing). V(O2)max was lower in patients than in control subjects
      (1.3 +/- 0.5 L/min vs 2.3 +/- 0.6 L/min) (p< 0.05). Smaller relative increases in
      cardiac index for similar increases in relative exercise intensities were found
      in patients (33% V(O2)max, 73% vs 116%; 66% V(O2)max, 115% vs 192%), as a result
      of smaller increases in stroke index from rest (33% V(O2)max, 33% vs 54%; 66%
      V(O2)max, 33% vs 69%; p< 0.05). Similarly, despite normal resting systolic
      function, patients exhibited a lower stroke index and higher heart rate for any
      given value of oxygen uptake (milliliters per minute per square meter). Children
      who had survived cancer exhibited stroke index impairment during exercise similar
      in intensity to that of recreational activities or play, attesting to a limited
      inotropic reserve.

PMID- 9023163
TI  - Effects of commonly used adrenergic agonists on left ventricular function and
      systemic vascular resistance in young piglets.
AB  - This study compared the effects of high-dose infusions of various adrenergic
      agonists on cardiovascular function in piglets. We hypothesized that agonists
      would have different effects on systolic, diastolic, and vascular functions. Nine
      anesthetized 3-week-old piglets underwent cardiac catheterization. Manometric and
      conductance catheters measured pressures and volumes. Data were acquired at rest
      and during infusions of epinephrine, norepinephrine, dopamine, dobutamine,
      isoproterenol, and phenylephrine. End-systolic elastance, preload-recruitable
      stroke work, cardiac output, the maximum and minimum derivatives of left
      ventricular pressure, the relaxation constant tau, peak filling rate, and end
      diastolic stiffness were obtained. Contractile efficiency and the cardiac
      output/pressure-volume area ratio were calculated. Regression was used for
      analysis of variance; p < 0.05 was considered significant. All agonists increased
      indexes of contractility. beta-Adrenergic agonists enhanced relaxation.
      Isoproterenol and dopamine increased efficiency. No drug changed diastolic
      stiffness. Therefore both alpha-adrenergic and beta-adrenergic agonists have
      inotropic effects in the 3-week-old piglet. Some beneficial effects of beta
      agonists on cardiac output may be due to enhancement of relaxation and to
      afterload reduction. Various agents exert different effects on the cardiovascular
      system, and these differences may be clinically important.

PMID- 9023164
TI  - Angiotensinogen gene polymorphism in Japanese patients with hypertrophic
      cardiomyopathy.
AB  - To examine the contribution of the renin-angiotensin system to hypertrophic
      cardiomyopathy (HCM), we studied 96 patients with HCM (mean age 50 years, 55%
      male), 105 of their unaffected siblings and offspring, and 160 healthy subjects
      without known hypertension and left ventricular hypertrophy (LVH) who were
      frequency matched to cases by age and sex. Patients were divided into familial or
      sporadic HCM (FHCM or SHCM) groups with or without affected members of their
      family. The region of interest in the angiotensinogen (AGT) gene, the missense
      mutation with methione-to-threonine amino acid substitution at codon 235 in
      angiotensinogen (M235T), was amplified by polymerase chain reaction with the use
      of allele-specific oligonucleotide primers flanking the polymorphic region of the
      AGT gene to amplify template deoxyribonucleic acid prepared from peripheral
      leukocytes. The T allele frequency was higher in the SHCM group than in
      unaffected siblings and offspring (88% vs 78%, X2 = 4.6, p < 0.05). The M allele
      frequency was higher in unaffected siblings and offspring than in patients with
      SHCM (23% vs 12%, X2 = 4.6, p < 0.05). The T allele frequency among unaffected
      siblings and offspring was similar to that observed in healthy subjects (78% vs
      78%). We conclude that HCM, especially in sporadic cases, is partially determined
      by genetic disposition. The molecular variant of angiotensinogen T235 seems to be
      a predisposing factor for cardiac hypertrophy in HCM and carries an approximately
      twofold increased risk.

PMID- 9023165
TI  - Expansion of Wiktor stents by oversizing versus high-pressure dilatation: a
      randomized, intracoronary ultrasound-controlled study.
AB  - Two strategies to achieve optimal expansion of Wiktor stents in coronary
      arteries, oversizing at normal balloon pressures (group 1) and high-pressure
      dilatation (group 2), were compared. We randomly assigned 20 symptomatic patients
      with de novo coronary artery stenoses of <15 mm length to one of the two
      treatment groups. Intracoronary ultrasound catheter pull-backs after stent
      implantation showed incomplete stent attachment with one or two struts protruding
      into the vessel lumen in 3 of 10 patients in group 1 but in no patient after high
      pressure dilatation in group 2 (p<0.01). Recross and high-pressure dilatation of
      the 3 stents in group 1 achieved complete attachment of all stents. Minimal
      luminal diameter was comparable between the groups (2.61 +/- 0.34 mm in group 1
      after stent delivery, and 2.68 +/- 0.45 mm in group 2 after high-pressure
      dilatation). Minimal luminal area (expressed as a percentage of the reference
      cross-sectional area) was slightly but insignificantly greater in the high
      pressure group (91.1% +/- 25.6% vs 85.5% +/- 15.1%). We conclude that
      implantation of Wiktor stents at normal inflation pressures does not reliably
      result in complete attachment of all struts to the vessel wall.

PMID- 9023166
TI  - Radiographic detection of single-leg fracture in Bjork-Shiley Convexo-Concave
      prosthetic valves: a phantom model study.
AB  - Cineradiography can identify patients with single-leg fractured Bjork-Shiley
      Convexo-Concave valves, although little is known about the sensitivity and
      specificity of this technique. We evaluated three normal and six (0 microm gap)
      single-leg fractured Bjork-Shiley valves that were placed in a working phantom
      model. Valves were randomly imaged a total of 33 times and duplicated into a 120
      valve series with a 1:9 ratio of abnormal/normal valves. Six reviewers
      independently graded each valve and demonstrated markedly different rates of
      identifying the fractured valves. Average sensitivity at the grade that
      clinically results in valve explanation was 47%. Among the normal valves, a
      correct identification was made 96% (range 91% to 99%) of the time. Present
      radiographic technology may have significant difficulty in identifying true
      single-leg fracture in Bjork-Shiley valves with limb separations that are common
      among clinically explanted valves.

PMID- 9023167
TI  - Rotational coronary atherectomy with adjunctive balloon angioplasty: evaluation
      of lumen enlargement by quantitative angiographic analysis.
AB  - To evaluate the mechanisms of lumen enlargement and the respective contributions
      of rotational coronary atherectomy (RA) and adjunctive percutaneous transluminal
      coronary balloon angioplasty (PTCA), serial measurements were recorded in 70
      consecutive patients by quantitative coronary angiography before RA, after RA,
      after adjunctive PTCA, and 24 hours later. Minimal luminal diameter (MLD)
      increased from 0.85 +/- 0.31 mm to 1.42 +/- 0.27 mm (p < 0.001) after RA and to
      2.20 +/- 0.46 mm (p < 0.001) after PTCA. Minimal luminal area (MLA) increased
      from 0.64 +/- 0.50 mm2 to 1.63 +/- 0.60 mm2 (p < 0.001) after RA and to 3.97 +/-
      1.68 mm2 (p < 0.001) after PTCA. Both 24-hour MLD and MLA showed a trend toward
      reduced values (2.07 +/- 0.45 mm and 3.52 +/- 1.70 mm2, respectively) when
      compared with immediate results after PTCA. The absolute gains in MLD after RA
      and after PTCA were 0.56 +/- 0.24 mm and 0.79 +/- 0.38 mm, respectively (p <
      0.01). The absolute gains in MLA after RA and after PTCA were 0.99 +/- 0.49 mm2
      and 2.34 +/- 1.41 mm2, respectively (p < 0.001). The respective contributions of
      RA and PTCA are highly variable, but in general, balloon dilatation accounts for
      most of the gain in lumen area and therefore is not an adjunctive but a primary
      technique.

PMID- 9023168
TI  - Angiographic predictors of neointimal thickening after successful coronary wall
      healing following percutaneous revascularization.
AB  - This study was undertaken to characterize, by intracoronary ultrasound technique,
      the neointimal thickening at follow-up of treated coronary segments after
      successful arterial wall repair and to compare the findings with serial
      angiographic studies. We selected for study 81 patients with single-vessel
      coronary disease successfully treated by percutaneous revascularization who were
      angiographically and ultrasonically reevaluated at a mean follow-up time of 22 +/
      21 months; 23 had been treated by balloon angioplasty, 27 by directional
      atherectomy, and 31 by elective Palmaz-Schatz stent implantation. The late
      maximal neointimal thickness varied between 0.1 and 1.5 mm (mean 0.65 +/- 0.31
      mm), and the neointimal area ranged between 0.97 and 14.9 mm2 (mean 5.19 +/- 3.14
      mm2). The neointimal repair was thinner in patients who obtained a better acute
      angiographic result immediately after treatment and in stented (3.4 +/- 1.8 mm2)
      versus dilated (7.8 +/- 4.1 mm2) or resected (5 +/- 1.6 mm2, p < 0.001) segments.
      On the contrary, the repaired neointimal layer was thicker in those patients who
      angiographically exhibited less late luminal loss or even expansion and in those
      evaluated after a longer time since treatment. The acute gain and the time
      influence resulted in independent predictors of the degree of neointimal
      thickness. These findings suggest that two reparative mechanisms of the coronary
      wall may operate in close relation.

PMID- 9023169
TI  - Transthoracic three-dimensional echocardiographic reconstruction of left and
      right ventricles: in vitro validation and comparison with magnetic resonance
      imaging.
AB  - Two-dimensional (2D) echocardiographic and angiographic measurements of
      ventricular volumes are limited by geometric assumptions concerning cavity shape.
      We compared in vitro the accuracy of a three-dimensional (3D) echocardiographic
      system suitable for transthoracic imaging to magnetic resonance imaging (MRI) in
      the measurement of left and right ventricular volumes. Ventricular cast volumes
      from 14 excised formalin-fixed sheep hearts filled with an agarose solution were
      compared with data derived from 3D echocardiography and MRI. Left and right
      ventricular volumes from 3D echocardiographic reconstructions agreed well with
      actual volumes without significant underestimation or overestimation. MRI
      progressively underestimated left ventricular volumes as these increased and
      systematically underestimated right ventricular volumes. Our echocardiographic
      system designed for 3D transthoracic imaging combines excellent measurements of
      left and right ventricular volumes and the computed reconstruction of tomographic
      slices with the full spatial resolution of the original 2D images. Thus in this
      in vitro model, 3D echocardiography exhibited greater accuracy than MRI.

PMID- 9023170
TI  - Presyncopal sympathetic withdrawal is the same in patients with vasodepressor
      syncope and controls who faint on head-up tilting.
AB  - Head-up tilt provokes vasodepressor syncope in patients with this disorder but
      may also cause fainting in unaffected subjects. The aims of this study were to
      examine autonomic function and sequential changes in heart rate variability and
      plasma catecholamines during graded head-up tilt in patients with vasodepressor
      syncope compared with healthy subjects. Studies were performed in 10 patients and
      15 control subjects. Eight negative controls completed the study; presyncope or
      syncope developed in seven positive controls and all 10 patients. The negative
      control group showed a progressive increase in mid-frequency from the supine
      position to end tilt. Patients and positive controls showed significant and
      similar falls in mid-frequency in the presyncope period. The rise in plasma
      norepinephrine was blunted in patients and positive controls, whereas plasma
      epinephrine increased more in these groups compared with the negative control
      group. In conclusion, the patterns of heart rate variability and catecholamine
      changes could not be distinguished in patients and positive control subjects.

PMID- 9023171
TI  - Diagnostic value of exercise electrocardiography and angina after coronary artery
      stenting. Benestent Study Group.
AB  - To determine whether metallic stent implantation within a coronary artery
      modifies the accuracy of angina or exercise test results in predicting stenosis,
      we studied 172 patients assigned to stent implantation and 153 patients assigned
      to balloon angioplasty enrolled in the Benestent trial comparing de novo stenting
      with conventional balloon angioplasty. Sensitivity and specificity curves were
      constructed for the prediction of percentage diameter stenosis and minimal lumen
      diameter. Receiver-operator curves were constructed for comparison of diagnostic
      accuracy. Identical exercise load and duration were achieved in the two groups,
      despite a better angiographic result in patients treated with a stent. Similarly,
      the diagnostic accuracy of clinical symptoms or exercise test results as a
      function of the angiographic results were similar in patients with and patients
      without a stent. The intersection points of the sensitivity and specificity
      curves for recurrent angina or ST-segment depression were 72% to 77%. The
      corresponding cut-off points for percentage diameter stenosis were, respectively,
      52% and 50% for patients with and without a stent (1.35 and 1.50 mm for minimal
      lumen diameter). We conclude that the presence of an intracoronary stent does not
      affect the diagnostic accuracy of recurrent angina or exercise-induced ST
      depression in predicting residual stenosis. We also conclude that exercise
      tolerance is similar after balloon angioplasty, with or without stenting, despite
      a better angiographic outcome in the group receiving a stent, suggesting a
      minimal threshold beyond which the patient is no longer at risk for ischemia
      during exercise.

PMID- 9023172
TI  - Hereditary bundle branch defect: right bundle branch blocks of different causes
      have different morphologic characteristics.
AB  - Hereditary bundle branch defect is an autosomal dominant genetic disease that, in
      a large Lebanese family, was mapped to the long arm of chromosome 19. Affected
      individuals have various combinations of conduction defects such as right bundle
      branch block, left or right QRS frontal-axis deviation, or atrioventricular
      blocks. We now further characterize this disease with the presentation of a two
      decade follow-up and analysis of electrocardiographic features and mutation
      carrier status. The conduction block may be overt in the first year of life, and
      among affected individuals, there is a worsening of the conduction block in 5% to
      15% of cases, leading to complete atrioventricular block and possibly to sudden
      death. A group of individuals had QRS anomalies in right precordial leads such as
      rsr's', rss', or rSr', which may account for partial right bundle branch blocks.
      In this group, which we referred to as having an "r' pattern," 53% were actually
      mutation carriers, and 19% evolved toward a complete fascicular block. By
      contrast, mutation carriers with a normal electrocardiogram remained normal. The
      QRS morphologic appearance in the right precordial leads of affected individuals
      and r' pattern mutation carriers is notable for the absence or weakness of
      negative forces resulting in a rsR' or rR' morphology. In addition, an r' pattern
      is highly suggestive of a mutation carrier status in the presence of a broad r
      wave in aVR and s in V6 or a frontal-axis deviation. Finally, mutation carriers
      demonstrate a conduction block significantly more often in males than females
      (75% and 50%, respectively). This incomplete penetrance and slow evolution
      suggest that the actual prevalence of hereditary bundle branch defect is very
      much underestimated.

PMID- 9023173
TI  - Echocardiographic diagnosis of anomalous origins of the pulmonary arteries from
      the pulmonary trunk (crossed pulmonary arteries).

PMID- 9023174
TI  - Iatrogenic coronary septal artery-to-right ventricular fistula complicating
      percutaneous transluminal coronary angioplasty with spontaneous resolution.

PMID- 9023175
TI  - Cloning and characterization of the Helicobacter pylori flbA gene, which codes
      for a membrane protein involved in coordinated expression of flagellar genes.
AB  - Flagellar motility has been shown to be an essential requirement for the ability
      of Helicobacter pylori to colonize the gastric mucosa. While some flagellar
      structural components have been studied in molecular detail, nothing was known
      about factors that play a role in the regulation of flagellar biogenesis. We have
      cloned and characterized an H. pylori homolog (named flbA) of the lcrD/flbF
      family of genes. Many proteins encoded by these genes are known to be involved in
      flagellar biogenesis or secretion of virulence-associated proteins via type III
      secretion systems. The H. pylori flbA gene (2,196 bp) is capable of coding for a
      predicted 732-amino-acid, 80.9-kDa protein that has marked sequence similarity
      with other known members of the LcrD/FlbF protein family. An isogenic strain with
      a mutation in the flbA gene was constructed by disruption of the gene with a
      kanamycin resistance cassette and electroporation-mediated allelic exchange
      mutagenesis. The mutant strain expressed neither the FlaA nor the FlaB flagellin
      protein. The expression of the FlgE hook protein was reduced in comparison with
      the wild-type strain, and the extent of this reduction was growth phase
      dependent. The flbA gene disruption was shown to downregulate the expression of
      these flagellar genes on the transcriptional level. The flbA mutants were
      aflagellate and completely nonmotile. Occasionally, assembled hook structures
      could be observed, indicating that export of axial flagellar filament components
      was still possible in the absence of the flbA gene product. The hydrophilic part
      of the FlbA protein was expressed in Escherichia coli, purified, and used to
      raise a polyclonal rabbit antiserum against the FlbA protein. Western blot
      experiments with this antiserum indicated that the FlbA protein is predominantly
      associated with the cytoplasmic membrane in H. pylori. The antiserum cross
      reacted with two other proteins (97 and 43 kDa) whose expression was not affected
      by the flbA gene disruption and which might represent further H. pylori homologs
      of the LcrD/FlbF protein family.

PMID- 9023177
TI  - Survival during exposure to the electrophilic reagent N-ethylmaleimide in
      Escherichia coli: role of KefB and KefC potassium channels.
AB  - The role of the KefB and KefC potassium efflux systems in protecting Escherichia
      coli cells against the toxic effects of the electrophile N-ethylmaleimide has
      been investigated. Activation of KefB and KefC aids the survival of cells exposed
      to high concentrations (> 100 microM) of NEM. High potassium concentrations
      reduce the protection afforded by activation of KefB and KefC, but the possession
      of these systems is still important under these conditions. The Kdp system, which
      confers sensitivity to the electrophile methylglyoxal, did not affect the
      survival of cells exposed to NEM. Survival is correlated with the reduction of
      the cytoplasmic pH upon activation of the channels. In particular, the kinetics
      of the intracellular pH (pHi) change are crucial to the retention of viability of
      cells exposed to NEM; slow acidification does not protect cells as effectively as
      rapid lowering of pHi. Cells treated with low levels of NEM (10 microM) recover
      faster if they activate KefB and KefC, and this correlates with changes in pHi.
      The pHi does not significantly alter the rate of NEM metabolism. The possible
      mechanisms by which protection against the electrophile is mediated are
      discussed.

PMID- 9023176
TI  - A role for cpeYZ in cyanobacterial phycoerythrin biosynthesis.
AB  - Pigment mutant strain FdR1 of the filamentous cyanobacterium Fremyella
      diplosiphon is characterized by constitutive synthesis of the phycobiliprotein
      phycoerythrin due to insertional inactivation of the rcaC regulatory gene by
      endogenous transposon Tn5469. Whereas the parental strain Fd33 harbors five
      genomic copies of Tn5469, cells of strain FdR1 harbor six genomic copies of the
      element; the sixth copy in FdR1 is localized to the rcaC gene. Electroporation of
      FdR1 cells yielded secondary pigment mutant strains FdR1E1 and FdR1E4, which
      identically exhibited the FdR1 phenotype with significantly reduced levels of
      phycoerythrin. In both FdR1E1 and FdR1E4, a seventh genomic copy of Tn5469 was
      localized to the cpeY gene of the sequenced but phenotypically uncharacterized
      cpeYZ gene set. This gene set is located downstream of the cpeBA operon which
      encodes the alpha and beta subunits of phycoerythrin. Complementation experiments
      correlated cpeYZ activity to the phenotype of strains FdR1E1 and FdR1E4. The
      predicted CpeY and CpeZ proteins share significant sequence identity with the
      products of homologous cpeY and cpeZ genes reported for Pseudanabaena sp. strain
      PCC 7409 and Synechococcus sp. strain WH 8020, both of which synthesize
      phycoerythrin. The CpeY and CpeZ proteins belong to a family of structurally
      related cyanobacterial proteins that includes the subunits of the CpcE/CpcF
      phycocyanin alpha-subunit lyase of Synechococcus sp. strain PCC 7002 and the
      subunits of the PecE/PecF phycoerythrocyanin alpha-subunit lyase of Anabaena sp.
      strain PCC 7120. Phycobilisomes isolated from mutant strains FdR1E1 and FdR1E4
      contained equal amounts of chromophorylated alpha and beta subunits of
      phycoerythrin at 46% of the levels of the parental strain FdR1. These results
      suggest that the cpeYZ gene products function in phycoerythrin synthesis,
      possibly as a lyase involved in the attachment of phycoerythrobilin to the alpha
      or beta subunit.

PMID- 9023178
TI  - Genetic characterization of the pdu operon: use of 1,2-propanediol in Salmonella
      typhimurium.
AB  - Salmonella typhimurium is able to catabolize 1,2-propanediol for use as the sole
      carbon and energy source; the first enzyme of this pathway requires the cofactor
      adenosyl cobalamin (Ado-B12). Surprisingly, Salmonella can use propanediol as the
      sole carbon source only in the presence of oxygen but can synthesize Ado-B12 only
      anaerobically. To understand this situation, we have studied the pdu operon,
      which encodes proteins for propanediol degradation. A set of pdu mutants
      defective in aerobic degradation of propanediol (with exogenous vitamin B12)
      defines four distinct complementation groups. Mutations in two of these groups
      (pduC and pduD) eliminate propanediol dehydratase activity. Based on mutant
      phenotypes, a third complementation group (pduG) appears to encode a cobalamin
      adenosyl transferase activity. No function has been assigned to the pduJ
      complementation group. Propionaldehyde dehydrogenase activity is eliminated by
      mutations in any of the four identified complementation groups, suggesting that
      this activity may require a complex of proteins encoded by the operon. None of
      the mutations analyzed affects either of the first two genes of the operon (pduA
      and pduB), which were identified by DNA sequence analysis. Available data suggest
      that the pdu operon includes enough DNA for about 15 genes and that the four
      genetically identified genes are the only ones required for aerobic use of
      propanediol.

PMID- 9023179
TI  - X-ray photoelectron spectroscopy analysis of whole cells and isolated cell walls
      of gram-positive bacteria: comparison with biochemical analysis.
AB  - The surface chemical composition of whole cells and isolated cell walls of four
      coryneform bacteria and of a Bacillus brevis strain has been determined by X-ray
      photoelectron spectroscopy (XPS). The XPS data were converted into concentrations
      of model compounds: peptides, polysaccharides, and hydrocarbonlike compounds. The
      composition of the surface of B. brevis differed markedly from that of
      coryneforms: the peptide concentration was about twice higher in the former case,
      which is attributed to the presence of an S-layer at the cell surface; in
      contrast, the surface of coryneforms was rich in hydrocarbonlike compounds (about
      40%), which was concomitant with a high water contact angle. The peptide surface
      concentration of the isolated cell walls of the five strains deduced from XPS
      data fitted well with the total peptide content determined by biochemical
      analysis, which supports the validity of XPS to determine the overall
      macromolecular composition of the bacterial cell surface. Compared to biochemical
      analysis of isolated cell walls, XPS analysis of whole cells provides information
      which concerns directly the cell surface (2- to 5-nm-thick layer) and is less
      subject to alteration via losses of cell wall constituents or contamination by
      intracellular compounds.

PMID- 9023180
TI  - The Cpx two-component signal transduction pathway is activated in Escherichia
      coli mutant strains lacking phosphatidylethanolamine.
AB  - The CpxA-CpxR two-component signal transduction pathway of Escherichia coli was
      studied in a mutant (pss-93) lacking phosphatidylethanolamine (PE). Several
      properties of this mutant are comparable to phenotypes of cpxA point mutants,
      indicating that this two-component pathway is activated in PE-deficient cells. In
      contrast to point mutants, cpx operon null mutants have a wild-type phenotype. By
      use of this information, a cpx operon null allele was introduced into a pss-93
      mutant. Certain altered properties of PE-deficient mutants, which were consistent
      with activation of the Cpx pathway, returned to the wild-type phenotype, namely,
      active accumulation of proline and thiomethyl-beta-D-galactopyranoside was
      partially restored to wild-type levels, increased resistance to amikacin returned
      to wild-type sensitivity, and high levels of degP expression returned to
      repressed wild-type levels. Elevated levels of acetyl phosphate and nlpE gene
      product can result in activation of the Cpx pathway. However, inactivation of the
      nlpE gene or mutations eliminating the ability to make acetyl phosphate did not
      alter the high level of degP expression in pss-93 mutants. We propose that the
      lack of PE results in an alteration in cell envelope structure or physical
      properties, leading to direct activation of the Cpx pathway.

PMID- 9023181
TI  - Altered transcription activation specificity of a mutant form of Bacillus
      subtilis GltR, a LysR family member.
AB  - A mutation (gltR24) that allows Bacillus subtilis glutamate synthase (gltAB) gene
      expression in the absence of its positive regulator, GltC, was identified.
      Cloning and sequencing of the gltR gene revealed that the putative gltR product
      belongs to the LysR family of transcriptional regulators and is thus related to
      GltC. A null mutation in gltR had no effect on gltAB expression under any
      environmental condition tested, suggesting that gltR24 is a gain-of-function
      mutation. GltR24-dependent transcription of gltAB, initiated at the same base
      pair as GltC-dependent transcription, was responsive to the nitrogen source in
      the medium and required the integrity of sequences upstream of the gltAB promoter
      that are also necessary for GltC-dependent expression. Expression of the gltC
      gene, transcribed divergently from gltA from an overlapping promoter, was not
      affected by GltR. Both wild-type GltR and GltR24 negatively regulated their own
      expression. The gltR gene was mapped to 233 degrees on the B. subtilis
      chromosome, very close to the azlB locus.

PMID- 9023182
TI  - Enzymology of oxidation of tropic acid to phenylacetic acid in metabolism of
      atropine by Pseudomonas sp. strain AT3.
AB  - Pseudomonas sp. strain AT3 grew with dl-tropic acid, the aromatic component of
      the alkaloid atropine, as the sole source of carbon and energy. Tropic acid-grown
      cells rapidly oxidized the growth substrate, phenylacetaldehyde, and phenylacetic
      acid. Crude cell extracts, prepared from dl-tropic acid-grown cells, contained
      two NAD+-linked dehydrogenases which were separated by ion-exchange
      chromatography and shown to be specific for their respective substrates, dl
      tropic acid and phenylacetaldehyde. Phenylacetaldehyde dehydrogenase was
      relatively unstable. The stable tropic acid dehydrogenase was purified to
      homogeneity by a combination of ion-exchange, molecular-sieve, and affinity
      chromatography. It had a pH optimum of 9.5 and was equally active with both
      enantiomers of tropic acid, and at this pH, phenylacetaldehyde was the only
      detectable product of tropic acid oxidation. The formation of phenylacetaldehyde
      from tropic acid requires, in addition to dehydrogenation, a decarboxylation
      step. By analogy with NAD+-specific isocitrate and malate dehydrogenases,
      phenylmalonic semialdehyde, a 3-oxoacid, would be expected to be the precursor of
      phenylacetaldehyde. Other workers have established that isocitrate and malate
      dehydrogenases catalyze the decarboxylation of enzyme-bound or added 3-oxoacid
      intermediates, a reaction that requires Mn2+ or Mg2+ ions. Studies with tropic
      acid dehydrogenase were hampered by lack of availability of phenylmalonic
      semialdehyde, but in the absence of added divalent metal ions, both enantiomers
      of tropic acid were completely oxidized and we have not, by a number of
      approaches, found any evidence for the transient accumulation of phenylmalonic
      semialdehyde.

PMID- 9023183
TI  - Critical base pairs and amino acid residues for protein-DNA interaction between
      the TyrR protein and tyrP operator of Escherichia coli.
AB  - In Escherichia coli K-12, the repression of tyrP requires the binding of the TyrR
      protein to the operator in the presence of coeffectors, tyrosine and ATP. This
      operator contains two 22-bp palindromic sequences which are termed TyrR boxes.
      Methylation, uracil, and ethylation interference experiments were used to
      identify the important sites in the TyrR boxes that make contacts with the TyrR
      protein. Methylation interference studies demonstrated that guanines at positions
      +8, -5, and -8 of the strong TyrR box and positions +8, -4, and -8 of the weak
      box are close to the TyrR protein. Uracil interference revealed that strong van
      der Waals contacts are made by the thymines at position -7 and +5 of the top
      strands of both strong and weak boxes and that weaker contacts are made by the
      thymines at positions +7 (strong box) and -5 and +7 (weak box) of the bottom
      strand. In addition, ethylation interference suggested that the phosphate
      backbone contacts are located at the end and central regions of the palindrome.
      These findings are supported by our results derived from studies of symmetrical
      mutations of the tyrP strong box. Overall, the results confirm the critical
      importance of the invariant (G x C)(C x G)8 base pairs for TyrR recognition and
      also indicate that interactions with (T x A)(A x T)7 are of major importance. In
      contrast, mutations in other positions result in weaker effects on the binding
      affinity of TyrR protein, indicating that these positions play a lesser role in
      TyrR protein recognition. Alanine scanning of both helices of the putative helix
      turn-helix DNA-binding motif of TyrR protein has identified those amino acids
      whose side chains play an essential role in protein structure and DNA binding.

PMID- 9023184
TI  - Mutational analysis of protein binding sites involved in formation of the
      bacteriophage lambda attL complex.
AB  - Bacteriophage lambda site-specific recombination requires the formation of higher
      order protein-DNA complexes to accomplish synapsis of the partner attachment
      (att) sites as well as for the regulation of the integration and excision
      reactions. The att sites are composed of a core region, the actual site of strand
      exchange, and flanking arm regions. The attL site consists of two core sites (C
      and C'), an integration host factor (IHF) binding site (H'), and three contiguous
      Int binding arm sites (P'1, P'2, and P'3). In this study, we employed
      bacteriophage P22 challenge phages to determine which protein binding sites
      participate in attL complex formation in vivo. The C', H', and P'1 sites were
      critical, because mutations in these sites severely disrupted formation of the
      attL complex. Mutations in the C and P'2 sites were less severe, and alteration
      of the P'3 site had no effect on complex formation. These results support a model
      in which IHF, bound to the H' site, bends the attL DNA so that the Int molecule
      bound to P'1 also interacts with the C' core site. This bridged complex, along
      with a second Int molecule bound to P'2, helps to stabilize the interaction of a
      third Int with the C core site. The results also indicate that nonspecific DNA
      binding is a significant component of the Int-core interactions and that the
      cooperativity of Int binding can overcome the effects of mutations in the
      individual arm sites and core sites.

PMID- 9023185
TI  - AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces
      cerevisiae.
AB  - Autophagocytosis is a starvation-induced process responsible for transport of
      cytoplasmic proteins to the vacuole. In Saccharomyces cerevisiae, autophagy is
      characterized by the phenotypic appearance of autophagic vesicles inside the
      vacuole of strains deficient in proteinase yscB. The AUT1 gene, essential for
      autophagy, was isolated by complementation of the sporulation deficiency of a
      diploid aut1-1 mutant strain by a yeast genomic library and characterized. AUT1
      is located on the right arm of chromosome XIV, 10 kb from the centromere, and
      encodes a protein of 310 amino acids, with an estimated molecular weight of 36
      kDa. Cells carrying a chromosomal deletion of AUT1 are defective in the
      starvation-induced bulk flow transport of cytoplasmic proteins to the vacuole.
      aut1 null mutant strains are completely viable but show decreased survival rates
      during starvation. Homozygous delta aut1 diploid cells fail to sporulate. The
      selective cytoplasm-to-vacuole transport of aminopeptidase I is blocked in
      logarithmically growing and in starved delta autl cells. Deletion of the AUT1
      gene had no obvious influence on secretion, fluid phase endocytosis, or vacuolar
      protein sorting. This supports the idea of autophagocytosis as being a novel
      route transporting proteins from the cytoplasm to the vacuole.

PMID- 9023186
TI  - Carbon source-dependent synthesis of SecB, a cytosolic chaperone involved in
      protein translocation across Escherichia coli membranes.
AB  - SecB is a cytosolic chaperone involved in protein translocation across
      cytoplasmic membranes in Escherichia coli. It has been shown to be required for
      efficient translocation of a subset of precursor proteins but is not essential
      for cell viability. This study investigated whether synthesis of SecB is growth
      rate dependent. Interestingly, the total amount of SecB synthesized in the cells
      was relatively small. Moreover, the levels of SecB were found to be carbon source
      dependent since more SecB was produced in cells grown in glycerol media than in
      cells grown in glucose media, regardless of the growth rate. This is in contrast
      to the other Sec proteins, whose synthesis is growth rate dependent and not
      related to glucose as a carbon source. In addition, cyclic AMP (cAMP) partially
      relieves the lower levels of SecB observed in glucose medium, a compensatory
      effect that depends on the presence of both cya and crp gene products. Thus, the
      glucose-dependent synthesis of SecB may be related to the cAMP-cAMP receptor
      protein complex-mediated activation.

PMID- 9023187
TI  - Conservation of msp, the gene encoding the major outer membrane protein of oral
      Treponema spp.
AB  - The major surface protein (Msp) of Treponema denticola has been implicated as a
      mediator of the interaction between the spirochete and the gingival epithelium in
      periodontal diseases. Previous studies showed that the Msp of T. denticola ATCC
      35405 had porin activity, depolarized epithelial cell membranes, bound to
      extracellular matrix components of epithelial cells, and formed a regular
      hexagonal surface array in the treponemal outer membrane. The gene encoding Msp
      in ATCC 35405 was recently cloned, sequenced, and expressed in Escherichia coli
      (J. C. Fenno, K.-H. Muller, and B. C. McBride, J. Bacteriol. 178:2489-2496,
      1996). In the present study, we identified genes encoding Msp-like proteins in
      several oral spirochetes. A prominent heat-modifiable Msp-like protein having an
      apparent molecular mass of between 43 and 64 kDa was present in all oral
      spirochete strains tested. Antibodies raised against the ATCC 35405 Msp reacted
      strongly with the Msp proteins of T. denticola ATCC 35404 and T. vincentii,
      reacted very weakly with the Msp protein of T. denticola ATCC 33520, and did not
      react with T. denticola OTK, T. socranskii, and T. pectinovorum. The msp loci of
      the T. denticola strains and T. vincentii were identified in analyses using PCR
      with oligonucleotide primers derived from the DNA sequence flanking msp in ATCC
      35405. Southern blot analysis showed at least three groups of related msp DNA
      sequences. Comparison of DNA sequences of the 5' and 3' ends of the msp genes
      showed high sequence homology in the flanking regions and signal peptide coding
      regions, while the homologies between regions encoding the mature peptide were as
      low as 50%. The entire msp DNA sequences of T. denticola ATCC 33520 and OTK were
      determined, and the deduced Msp amino acid sequences were compared to the
      sequence of the previously reported Msp of ATCC 35405. The results show that the
      msp locus is conserved in oral treponemes but that there are significant
      differences between the mature Msp peptides of different strains. Further studies
      of the antigenic domains, functional domains, and physical structures of Msp
      proteins, based on these results, will enhance understanding of the role of Msp
      in the cytopathology associated with oral spirochetes.

PMID- 9023188
TI  - Characterization and regulation of the gene encoding nitrite reductase in
      Rhodobacter sphaeroides 2.4.3.
AB  - Nitrite reductase catalyzes the reduction of nitrite to nitric oxide, the first
      step in denitrification to produce a gaseous product. We have cloned the gene
      nirK, which encodes the copper-type nitrite reductase from a denitrifying variant
      of Rhodobacter sphaeroides, strain 2.4.3. The deduced open reading frame has
      significant identity with other copper-type nitrite reductases. Analysis of the
      promoter region shows that transcription initiates 31 bases upstream of the
      translation start codon. The transcription initiation site is 43.5 bases
      downstream of a putative binding site for a transcriptional activator. Maximal
      expression of a nirK-lacZ construct in 2.4.3 requires both a low level of oxygen
      and the presence of a nitrogen oxide. nirK-lacZ expression was severely impaired
      in a nitrite reductase-deficient strain of 2.4.3. This suggests that nirK
      expression is dependent on nitrite reduction. The inability of microaerobically
      grown nitrite reductase-deficient cells to induce nirK-lacZ expression above
      basal levels in medium unamended with nitrate demonstrates that changes in oxygen
      concentrations are not sufficient to modulate nirK expression.

PMID- 9023189
TI  - Saccharomyces cerevisiae exhibits a yAP-1-mediated adaptive response to
      malondialdehyde.
AB  - Malondialdehyde (MDA) is a highly reactive aldehyde generally formed as a
      consequence of lipid peroxidation. MDA has been inferred to have mutagenic and
      cytotoxic roles and possibly to be a participant in the onset of atherosclerosis.
      Wild-type Saccharomyces cerevisiae acquires resistance to a lethal dose (5 mM) of
      MDA following prior exposure to a nonlethal concentration (1 mM). This response
      was completely inhibited by cycloheximide (50 microg ml(-1)), indicating a
      requirement for protein synthesis for adaptation. Furthermore, we have examined
      the roles of glutathione (GSH), mitochondrial function, and yAP-1-mediated
      transcription in conferring resistance and adaptation to MDA. A yap1 disruption
      mutant exhibited the greatest sensitivity and was unable to adapt to MDA,
      implicating yAP-1 in both the adaptive response and constitutive survival. The
      effect of MDA on GSH mutants indicated a role for GSH in initial resistance,
      whereas resistance acquired through adaptation was independent of GSH. Likewise,
      respiratory mutants (petite mutants) were sensitive to MDA but were still able to
      mount an adaptive response similar to that of the wild type, excluding
      mitochondria from any role in adaptation. MDA was detected in yeast cells by the
      thiobarbituric acid test and subsequent high-pressure liquid chromatography
      separation. Elevated levels were detected following treatment with hydrogen
      peroxide. However, the MDA-adaptive response was independent of that to H2O2.

PMID- 9023190
TI  - Differential inactivation of alcohol dehydrogenase isoenzymes in Zymomonas
      mobilis by oxygen.
AB  - Zymomonas mobilis is endowed with two isoenzymes of fermentative alcohol
      dehydrogenase, a zinc-containing enzyme (ADH I) and an iron-containing enzyme
      (ADH II). The activity of ADH I remains fully conserved, while ADH II activity
      decays when anaerobic cultures are shifted to aerobiosis. This differential
      response depends on the metal present on each isoenzyme, since pure preparations
      of ADH I are resistant to oxidative inactivation and preparations of zinc
      containing ADH II, obtained by incubation of pure ADH II with ZnCl2, showed no
      modification of the target for oxidative damage (His277-containing peptide). It
      was consistently found that the activity of the zinc-containing ADH II, once
      submitted to oxidative treatment, was fully restored when iron was reintroduced
      into the enzyme structure. These results indicate that zinc bound to these
      proteins plays an important role in the protection of their active centers
      against oxidative damage and may have relevant biochemical and physiological
      consequences in this species.

PMID- 9023191
TI  - Analysis of the boundaries of Salmonella pathogenicity island 2 and the
      corresponding chromosomal region of Escherichia coli K-12.
AB  - We recently identified a pathogenicity island (SPI2) located at 30.7 centisomes
      on the Salmonella typhimurium chromosome. SPI2 contains genes encoding a type III
      secretion system whose function is distinct from that of the type III secretion
      system encoded by a pathogenicity island (SPI1) at 63 centisomes which is
      involved in epithelial cell entry. An analysis of the boundaries of SPI2 and
      comparison with the corresponding region of the Escherichia coli chromosome
      revealed that SPI2 inserted adjacent to the tRNA(Val) gene. The E. coli
      chromosome contains 9 kb of DNA at the region corresponding to the SPI2 insertion
      point which appears to be absent in S. typhimurium. The distribution of SPI1 and
      SPI2 was examined in various Salmonella isolates. In contrast to type III
      secretion system genes of SPI1, those of SPI2 are not present in Salmonella
      bongori, which diverged at the first branch point in the Salmonella lineage.
      These and other data indicate that SPI2 was acquired by a Salmonella strain
      already harboring SPI1 by horizontal transfer from an unknown source.

PMID- 9023192
TI  - Cloning, sequencing, and analysis of a gene cluster from Chelatobacter heintzii
      ATCC 29600 encoding nitrilotriacetate monooxygenase and NADH:flavin
      mononucleotide oxidoreductase.
AB  - Nitrilotriacetate (NTA) is an important chelating agent in detergents and has
      also been used extensively in processing radionuclides. In Chelatobacter heintzii
      ATCC 29600, biodegradation of NTA is initiated by NTA monooxygenase that oxidizes
      NTA to iminodiacetate and glyoxylate. The NTA monooxygenase activity requires two
      component proteins, component A and component B, but the function of each
      component is unclear. We have cloned and sequenced a gene cluster encoding
      components A and B (nmoA and nmoB) and two additional open reading frames, nmoR
      and nmoT, downstream of nmoA. Based on sequence similarities, nmoR and nmoT
      probably encode a regulatory protein and a transposase, respectively. The NmoA
      sequence was similar to a monooxygenase that uses reduced flavin mononucleotide
      (FMNH2) as reductant; NmoB was similar to an NADH:flavin mononucleotide (FMN)
      oxidoreductase. On the basis of this information, we tested the function of each
      component. Purified component B was shown to be an NADH:FMN oxidoreductase, and
      its activity could be separated from that of component A. When the Photobacterium
      fischeri NADH:FMN oxidoreductase was substituted for component B in the complete
      reaction, NTA was oxidized, showing that the substrate specificity of the
      reaction resides in component A. Component A is therefore an NTA monooxygenase
      that uses FMNH2 and O2 to oxidize NTA, and component B is an NADH:FMN
      oxidoreductase that provides FMNH2 for NTA oxidation.

PMID- 9023193
TI  - Specific DNA cleavage mediated by the integrase of conjugative transposon Tn916.
AB  - The conjugative transposon Tn916 encodes a protein called INT(Tn916) which, based
      on DNA sequence comparisons, is a member of the integrase family of site-specific
      recombinases. Integrase proteins such as INT(lambda), FLP, and XERC/D that
      promote site-specific recombination use characteristic, conserved amino acid
      residues to catalyze the cleavage and ligation of DNA substrates during
      recombination. The reaction proceeds by a two-step transesterification reaction
      requiring the formation of a covalent protein-DNA intermediate. Different
      requirements for homology between recombining DNA sites during integrase-mediated
      site-specific recombination and Tn916 transposition suggest that INT(Tn916) may
      use a reaction mechanism different from that used by other integrase
      recombinases. We show that purified INT(Tn916) mediates specific cleavage of
      duplex DNA substrates containing the Tn916 transposon ends and adjacent bacterial
      sequences. Staggered cleavages occur at both ends of the transposon, resulting in
      5' hydroxyl protruding ends containing coupling sequences. These are sequences
      that are transferred with the transposon from donor to recipient during
      conjugative transposition. The nature of the cleavage products suggests that a
      covalent protein-DNA linkage occurs via a residue of INT(Tn916) and the 3'
      phosphate group of the DNA. INT(Tn916) alone is capable of executing the strand
      cleavage step required for recombination during Tn916 transposition, and this
      reaction probably occurs by a mechanism similar to that of other integrase family
      site-specific recombinases.

PMID- 9023194
TI  - Biological function of the dTDP-rhamnose synthesis pathway in Streptococcus
      mutans.
AB  - We have cloned a new gene locus that comprises three genes concerned with the
      biosynthesis of the serotype c-specific polysaccharide antigen in Streptococcus
      mutans. The genes encode proteins exhibiting significant homology to the rfbA,
      rfbB, and rfbD gene products that are involved in the anabolism of dTDP-L
      rhamnose from D-glucose-1-phosphate. This anabolism pathway pertains to
      biosynthesis of the O antigen of lipopolysaccharide in gram-negative bacteria.
      The cell extract of Escherichia coli expressing each of the cloned genes of S.
      mutans exhibited enzymatic activity corresponding to the homologous counterpart
      of the rfb gene products. Rhamnose was not detected in the cell wall preparation
      purified from the mutant in which each of the three cloned genes was
      insertionally inactivated. Rabbit antiserum against S. mutans serotype c-specific
      antigen did not react with the autoclaved extracts from these mutants. These
      results indicate that the gene products identified in the present study are
      involved in the dTDP-L-rhamnose synthesis pathway and that the pathway relates to
      the biosynthesis of the serotype-specific polysaccharide antigen of S. mutans.
      Southern hybridization analysis revealed that genes homologous to the cloned
      genes involved in the dTDP-L-rhamnose synthesis pathway were widely distributed
      in a variety of streptococci. This is the first report of the biological function
      of the dTDP-rhamnose pathway in streptococci.

PMID- 9023195
TI  - A conserved glutamate residue, Glu-257, is important for substrate binding and
      transport by the Escherichia coli mannitol permease.
AB  - The mannitol permease, or D-mannitol-specific enzyme II of the
      phosphoenolpyruvate-dependent carbohydrate phosphotransferase system (PTS) of
      Escherichia coli, both transports and phosphorylates its substrate. Previous
      analyses of the amino acid sequences of PTS permeases specific for various
      carbohydrates in different species of bacteria revealed several regions of
      similarity. The most highly conserved region includes a GIXE motif, in which the
      glutamate residue is completely conserved among the permeases that contain this
      motif. The corresponding residue in the E. coli mannitol permease is Glu-257,
      which is located in a large putative cytoplasmic loop of the transmembrane domain
      of the protein. We used site-directed mutagenesis to investigate the role of Glu
      257. The properties of proteins with mutations at position 257 suggest that a
      carboxylate side chain at this position is essential for mannitol binding. E257A
      and E257Q mutant proteins did not bind mannitol detectably, while the E257D
      mutant could still bind this substrate. Kinetic studies with the E257D mutant
      protein also showed that a glutamate residue at position 257 of this permease is
      specifically required for efficient mannitol transport. While the E257D permease
      phosphorylated mannitol with kinetic parameters similar to those of the wild-type
      protein, the Vmax for mannitol uptake by this mutant protein is less than 5% that
      of the wild type. These results suggest that Glu-257 of the mannitol permease and
      the corresponding glutamate residues of other PTS permeases play important roles
      both in binding the substrate and in transporting it through the membrane.

PMID- 9023196
TI  - Cloning and sequence of cymA, a gene encoding a tetraheme cytochrome c required
      for reduction of iron(III), fumarate, and nitrate by Shewanella putrefaciens MR
      1.
AB  - The cymA gene, which encodes a tetraheme cytochrome c, was cloned from Shewanella
      putrefaciens MR-1. This gene complemented a mutant which had a TnphoA insertion
      in cymA and which was deficient in the respiratory reduction of iron(III),
      nitrate, fumarate, and manganese(IV). The 561-bp nucleotide sequence of cymA
      encodes a protein of 187 amino acids with a predicted molecular mass of 20.8 kDa.
      No N-terminal signal sequence was readily apparent; consistent with this, a
      cytochrome with a size of 21 kDa was detected in the wild type but was absent in
      the insertional mutant. The cymA gene is transcribed into an mRNA; the major
      transcript was approximately 790 bases, suggesting that it is not part of a
      multicistronic operon. This RNA transcript was not detected in the cymA mutant.
      The CymA protein was found in the cytoplasmic membrane and soluble fraction of MR
      1, and it shares partial amino acid sequence homology with multiheme c-type
      cytochromes from other bacteria. These cytochromes are ostensibly involved in the
      transfer of electrons from the cytoplasmic membrane to acceptors in the
      periplasm. The localization of the fumarate and iron(III) reductases to the
      periplasm and outer membrane of MR-1, respectively, suggests the possibility of a
      similar electron transfer role for CymA.

PMID- 9023197
TI  - The dnaK operon of Bacillus subtilis is heptacistronic.
AB  - In 1992, we described the cloning and sequencing of the dnaK locus of Bacillus
      subtilis which, together with transcriptional studies, implied a tetracistronic
      structure of the operon consisting of the genes hrcA, grpE, dnaK, and dnaJ. We
      have repeated the Northern blot analysis, this time using riboprobes instead of
      oligonucleotides, and have detected a heat-inducible 8-kb transcript, suggesting
      the existence of additional heat shock genes downstream of dnaJ. Cloning and
      sequencing of that region revealed the existence of three novel heat shock genes
      named orf35, orf28, and orf50, extending the tetra- into a heptacistronic operon.
      This is now the largest dnaK operon to be described to date. The three new genes
      are transcribed as a part of the entire dnaK operon (8.0-kb heptacistronic heat
      inducible transcript) and as part of a suboperon starting at an internal
      vegetative promoter immediately upstream of dnaJ (4.3-kb tetracistronic non-heat
      inducible transcript). In addition, the Northern blot analysis detected several
      processing products of these two primary transcripts. To demonstrate the
      existence of the internal promoter, a DNA fragment containing this putative
      promoter structure was inserted upstream of a promoterless bgaB gene, resulting
      in the synthesis of beta-galactosidase. Challenging this transcriptional fusion
      with various stress factors did not result in the activation of this promoter. To
      assign a biological function to the three novel genes, they have each been
      inactivated by the insertion of a cat cassette. All of the mutants were viable,
      and furthermore, these genes are (i) not essential for growth at high
      temperatures, (ii) not involved in the regulation of the heat shock response, and
      (iii) sporulation proficient. Blocking transcription of the suboperon from the
      upstream heat-inducible promoter did not impair growth and viability at high
      temperatures.

PMID- 9023198
TI  - Functional domains of Agrobacterium tumefaciens single-stranded DNA-binding
      protein VirE2.
AB  - The transferred DNA (T-DNA) portion of the Agrobacterium tumefaciens tumor
      inducing (Ti) plasmid enters infected plant cells and integrates into plant
      nuclear DNA. Direct repeats define the T-DNA ends; transfer begins when the VirD2
      endonuclease produces a site-specific nick in the right-hand border repeat and
      attaches to the 5' end of the nicked strand. Subsequent events liberate the lower
      strand of the T-DNA from the Ti plasmid, producing single-stranded DNA molecules
      (T strands) that are covalently linked to VirD2 at their 5' ends. A. tumefaciens
      appears to transfer T-DNA into plant cells as a T-strand-VirD2 complex. The
      bacterium also transports VirE2, a cooperative single-stranded DNA-binding
      protein, into plant cells during infection. Both VirD2 and VirE2 contain nuclear
      localization signals that may direct these proteins, and bound T strands, into
      plant nuclei. Here we report the locations of functional regions of VirE2
      identified by eight insertions of XhoI linker oligonucleotides, and one deletion
      mutation, throughout virE2. We examined the effects of these mutations on
      virulence, single-stranded DNA (ssDNA) binding, and accumulation of VirE2 in A.
      tumefaciens. Two of the mutations in the C-terminal half of VirE2 eliminated
      ssDNA binding, whereas two insertions in the N-terminal half altered
      cooperativity. Four of the mutations, distributed throughout virE2, decreased the
      stability of VirE2 in A. tumefaciens. In addition, we isolated a mutation in the
      central region of VirE2 that decreased tumorigenicity but did not affect ssDNA
      binding or VirE2 accumulation. This mutation may affect export of VirE2 into
      plant cells or nuclear localization of VirE2, or it may affect an uncharacterized
      activity of VirE2.

PMID- 9023199
TI  - Molecular and phylogenetic characterization of isopropylmalate dehydrogenase of a
      thermoacidophilic archaeon, Sulfolobus sp. strain 7.
AB  - The archaeal leuB gene encoding isopropylmalate dehydrogenase of Sulfolobus sp.
      strain 7 was cloned, sequenced, and expressed in Escherichia coli. The
      recombinant Sulfolobus sp. enzyme was extremely stable to heat. The substrate and
      coenzyme specificities of the archaeal enzyme resembled those of the bacterial
      counterparts. Sedimentation equilibrium analysis supported an earlier proposal
      that the archaeal enzyme is homotetrameric, although the corresponding enzymes
      studied so far have been reported to be dimeric. Phylogenetic analyses suggested
      that the archaeal enzyme is homologous to mitochondrial NAD-dependent isocitrate
      dehydrogenases (which are tetrameric or octameric) as well as to isopropylmalate
      dehydrogenases from other sources. These results suggested that the present
      enzyme is the most primitive among isopropylmalate dehydrogenases belonging in
      the decarboxylating dehydrogenase family.

PMID- 9023200
TI  - Biochemical and serological evidence for an RNase E-like activity in halophilic
      Archaea.
AB  - Endoribonuclease RNase E appears to control the rate-limiting step that mediates
      the degradation of many mRNA species in bacteria. In this work, an RNase E-like
      activity in Archaea is described. An endoribonucleolytic activity from the
      extreme halophile Haloarcula marismortui showed the same RNA substrate
      specificity as the Escherichia coli RNase E and cross-reacted with a monoclonal
      antibody raised against E. coli RNase E. The archaeal RNase E activity was
      partially purified from the extreme halophilic cells and shown, contrary to the
      E. coli enzyme, to require a high salt concentration for cleavage specificity and
      stability. These data indicate that a halophilic RNA processing enzyme can
      specifically recognize and cleave mRNA from E. coli in an extremely salty
      environment (3 M KCI). Having recently been shown in mammalian cells (A.
      Wennborg, B. Sohlberg, D. Angerer, G. Klein, and A. von Gabain, Proc. Natl. Acad.
      Sci. USA 92:7322-7326, 1995), RNase E-like activity has now been identified in
      all three evolutionary domains: Archaea, Bacteria, and Eukarya. This strongly
      suggests that mRNA decay mechanisms are highly conserved despite quite different
      environmental conditions.

PMID- 9023201
TI  - Utilization of phosphocholine from extracellular complex polysaccharide as a
      source of cytoplasmic choline derivatives in Penicillium fellutanum.
AB  - Penicillium fellutanum produces a phosphorylated, choline-containing
      extracellular polysaccharide, peptidophosphogalactomannan (pP(x)GM) [where x is
      the number of phosphodiester residues]). The 13C-methyl-labeled pP(x)GM ([methyl
      13C]pP(x)GM) was prepared from the cultures supplemented with L-[methyl
      13C]methionine and was used as a probe to monitor the fate of phosphocholine in
      this polymer. The addition of [methyl-13C]pP(x)GM to growing cultures in low
      phosphate medium resulted in the disappearance within 5 days of [methyl
      13C]phosphocholine and N,N'-dimethylphosphoethanolamine from the added [methyl
      13C]pP(x)GM. Two 13C-methyl-enriched cytoplasmic solutes, choline-O-sulfate and
      glycine betaine, were found in mycelial extracts, suggesting that phosphocholine
      containing extracellular pP(x)GM of P. fellutanum is a precursor of intracellular
      choline-O-sulfate and glycine betaine. The mycelia cultured in low-phosphate (2
      mM) medium contained glycine betaine and 1.5-fold more choline-O-sulfate than
      those grown in high-phosphate (20 mM) medium. The high levels of extracellular
      nonspecific phosphocholine:phosphocholine hydrolase and acid phosphomonoesterase
      observed in the low-phosphate culture medium are likely related to the release of
      phosphocholine from pP(x)GM and hydrolysis of phosphocholine, respectively. These
      results suggest that extracellular pP(x)GM of P. fellutanum provides phosphate
      needed as the environment becomes depleted of this nutrient. Choline, in excess
      of that needed immediately, is stored in the cytoplasm in forms that can be
      reutilized.

PMID- 9023202
TI  - Purification and molecular characterization of glycylglycine endopeptidase
      produced by Staphylococcus capitis EPK1.
AB  - A novel staphylolytic enzyme, ALE-1, acting on Staphylococcus aureus, was
      purified from a Staphylococcus capitis EPK1 culture supernatant. The optimal pH
      range for staphylolytic activity was 7 to 9. ALE-1 contains one Zn2+ atom per
      molecule. Analysis of peptidoglycan fragments released by ALE-1 indicated that
      the enzyme is a glycylglycine endopeptidase. The effects of various modulators
      were determined, and we found that o-phenanthroline, iodoacetic acid,
      diethylpyrocarbonate, and Cu2+ reduced the staphylolytic activity of ALE-1. beta
      Casein, elastin, and pentaglycine were poor substrates for ALE-1. Molecular
      cloning data revealed that ALE-1 is composed of 362 amino acid residues and is
      synthesized as a precursor protein which is cleaved after Ala at position 35,
      thus producing a mature ALE-1 of 35.6 kDa. The primary structure of mature ALE-1
      is very similar to the proenzyme form of lysostaphin. It has the modular design
      of an N-terminal domain of tandem repeats of a 13-amino-acid sequence fused to
      the active site containing C-terminal domain. Unlike lysostaphin, ALE-1 does not
      undergo processing of the N-terminal repeat domain in broth culture. ale-1 is
      encoded on the plasmid. Protein homology search suggested that ALE-1 and
      lysostaphin are members of the novel Zn2+ protease family with a homologous 38
      amino-acid-long motif, Tyr-X-His-X(11)-Val-X(12/20)-Gly-X(5-6)-His.

PMID- 9023203
TI  - VirB1, a component of the T-complex transfer machinery of Agrobacterium
      tumefaciens, is processed to a C-terminal secreted product, VirB1.
AB  - During genetic transformation of plant cells by Agrobacterium tumefaciens, 11
      VirB proteins and VirD4 are proposed to form a transmembrane bridge to transfer a
      DNA-protein complex (T-complex) into the plant cytoplasm. In this study, the
      localization of the first product of the virB operon, VirB1, was studied in
      detail. While full-length VirB1 localized mostly to the inner membrane, an
      immunoreactive VirB1 product was found as soluble processed form, designated
      VirB1*. Equal amounts of VirB1* could be detected in concentrated culture
      supernatants versus associated with the cell. VirB1* was purified from the
      supernatant of vir-induced cells by ammonium sulfate precipitation and Q
      Sepharose chromatography. Sequence analysis of the N terminus of VirB1* localized
      the processing site after amino acid 172 of VirB1. Cell-associated VirB1* was
      partly removed by vortexing, suggesting a loose association with the cell or
      active secretion. However, cross-linking and coimmunoprecipitation showed a close
      association of cell-bound VirB1* with the VirB9-VirB7 heterodimer, a membrane
      associated component of the T-complex transfer machinery. Homologies of the N
      terminal part of VirB1 to bacterial transglycosylases suggest that it may assist
      T-complex transfer by local lysis of the bacterial cell wall, whereas the exposed
      localization of the C-terminal processing product VirB1* predicts direct
      interaction with the plant. Thus, VirB1 may be a bifunctional protein where both
      parts have different functions in T-complex transfer from Agrobacterium to plant
      cells.

PMID- 9023204
TI  - The lipoprotein VirB7 interacts with VirB9 in the membranes of Agrobacterium
      tumefaciens.
AB  - VirB9 and VirB7 are essential components of the putative VirB membrane channel
      required for transfer of the T-complex from Agrobacterium tumefaciens into
      plants. In this report, we present a biochemical analysis of their interaction
      and cellular localization. A comparison of relative electrophoretic mobilities
      under nonreducing and reducing conditions suggested that they form thiol
      sensitive complexes with other proteins. Two-dimensional gel electrophoresis
      identified one complex as a heterodimer of VirB9 and VirB7 covalently linked by a
      disulfide bond, as well as VirB7 homodimers and monomers. Immunoprecipitation
      with VirB9-specific antiserum isolated the heterodimeric VirB9-VirB7 complex.
      Incubation with reducing agent split the complex into its constituent VirB9 and
      VirB7, which further confirmed linkage via cysteine residues. The interaction
      between VirB9 and VirB7 also was observed in the yeast two-hybrid system.
      Membrane attachment of VirB9-VirB7 may be conferred by lipoprotein modification,
      since labeling with [3H]palmitic acid in A. tumefaciens verified that VirB7 is a
      lipoprotein associated with VirB9. VirB9 and VirB7 showed equal distribution
      between inner and outer membranes, in accord with their proposed association with
      the transmembrane VirB complex.

PMID- 9023205
TI  - Role of enzymes of homologous recombination in illegitimate plasmid recombination
      in Bacillus subtilis.
AB  - The structural stability of plasmid pGP1, which encodes a fusion between the
      penicillinase gene (penP) of Bacillus licheniformis and the Escherichia coli lacZ
      gene, was investigated in Bacillus subtilis strains expressing mutated subunits
      of the ATP-dependent nuclease, AddAB, and strains lacking the major recombination
      enzyme, RecA. Strains carrying a mutation in the ATP-binding site of the AddB
      subunit exhibited high levels of plasmid instability, whereas a comparable
      mutation in the A subunit did not affect plasmid stability. Using an alternative
      plasmid system, pGP100, we were able to demonstrate that the differences in
      stability reflected differences in initial recombination frequencies. Based on a
      comparison of endpoint sequences observed in the various hosts, we speculate that
      at least two different mechanisms underlie the deletion events involved, the
      first (type I) occurring between nonrepeated sequences, and the second (type II)
      occurring between short direct repeats (DRs). The latter event was independent of
      single-strand replication intermediates and the mode of replication and possibly
      requires the introduction of double-strand breaks (DSBs) between the repeats. In
      the absence of functional AddAB complex, or the AddB subunit, DSBs are likely to
      be processed via a recA-independent mechanism, resulting in intramolecular
      recombination between the DRs. In wild-type cells, such DSBs are supposed to be
      either repaired by a mechanism involving AddAB-dependent recombination or
      degraded by the AddAB-associated exonuclease activity. Plasmid stability assays
      in a recA mutant showed that (i) the level of deletion formation was considerably
      higher in this host and (ii) that deletions between short DRs occurred at higher
      frequencies than those described previously for the parental strain. We propose
      that in wild-type cells, the recA gene product is involved in recombinational
      repair of DSBs.

PMID- 9023206
TI  - Sequence analysis and recombinant expression of a 28-kilodalton Treponema
      pallidum subsp. pallidum rare outer membrane protein (Tromp2).
AB  - In this study, we report the cloning, sequencing, and expression of the gene
      encoding a 28-kDa Treponema pallidum subsp. pallidum rare outer membrane protein
      (TROMP), designated Tromp2. The tromp2 gene encodes a precursor protein of 242
      amino acids including a putative signal peptide of 24 amino acids ending in a
      type I signal peptidase cleavage site of Leu-Ala-Ala. The mature protein of 218
      amino acids has a calculated molecular weight of 24,759 and a calculated pI of
      7.3. The predicted secondary structure of Tromp2 shows nine transmembrane
      segments of amphipathic beta-sheets typical of outer membrane proteins.
      Recombinant Tromp2 (rTromp2) was expressed with its native signal peptide, using
      a tightly regulated T7 RNA polymerase expression vector. Under high-level
      expression conditions, rTromp2 fractionated exclusively with the Escherichia coli
      outer membrane. Antiserum raised against rTromp2 was generated and used to
      identify native Tromp2 in cellular fractionations. Following Triton X-114
      extraction and phase separation of T. pallidum, the 28-kDa Tromp2 protein was
      detected prominently in the detergent phase. Alkali and high-salt treatment of
      purified outer membrane from T. pallidum, conditions which remove peripherally
      associated membrane proteins, demonstrated that Tromp2 is an integral membrane
      protein. Whole-mount immunoelectron microscopy of E. coli cells expressing
      rTromp2 showed specific surface antibody binding. These findings demonstrate that
      Tromp2 is a membrane-spanning outer membrane protein, the second such protein to
      be identified for T. pallidum.

PMID- 9023207
TI  - DNA-binding determinants of sigma 54 as deduced from libraries of mutations.
AB  - PCR mutagenesis was used to obtain libraries of mutations in the region between
      amino acids 300 and 400 in the DNA-binding domain of Escherichia coli sigma 54.
      Two hundred changes that did not alter function were identified. These were
      compared with a somewhat smaller number of changes that did alter function.
      Several important regions were identified. Single point mutations in two of
      these, near amino acids 363 and 383, destroyed the ability of sigma to bind DNA,
      as assayed by band shift analysis. A third segment from amino acids 327 to 347 is
      also a candidate for contributing to DNA binding. Comparison with data in the
      literature leads to testable proposals for the complex mode of DNA binding that
      is associated with sigma 54.

PMID- 9023208
TI  - Further characterization and in situ localization of chain-like aggregates of the
      gliding bacteria Myxococcus fulvus and Myxococcus xanthus.
AB  - For the first time, chain-like aggregates, called "strands," have been enriched
      from crude cell wall preparations of liquid-grown vegetative cells of two strains
      of Myxococcus xanthus. These strands are highly isomorphic to macromolecular
      structures, previously described for Myxococcus fulvus (Lunsdorf and Reichenbach,
      J. Gen. Microbiol. 135:1633-1641, 1989). The strands are morphologically composed
      of ring elements, consisting of six or more peripheral protein masses and
      possibly three small central masses. The ring elements are linked by two parallel
      strings of filamentous proteins, called elongated elements, which keep the ring
      elements at a constant distance. The overall dimensions of the ring elements are
      16.6 +/- 1.0 nm (n = 55) for M. xanthus Mx x48 and 16.4 +/- 1.5 nm (n = 37) for
      M. xanthus DK 1622. The distance between the ring elements, as a measure of the
      length of the elongated elements, is 16.6 +/- 1.1 nm (n = 59) for strain Mx x48
      and 15.5 +/- 0.6 nm (n = 41) for strain DK 1622. Characteristically, the strands
      and oligomeric forms thereof show a strict association with the outer membrane.
      In situ studies of freeze-fractured cells of M. fulvus showed ring elements,
      isomorphic to those described for M. xanthus, within the periplasm; they appeared
      in parallel rows just below the outer membrane but not in direct contact with the
      cytoplasmic membrane. A three-dimensional model summarizes the morphological
      data. It is hypothesized that the chain-like strands, as building blocks of a
      more complex belt-like continuum, represent the peripheral part of the gliding
      machinery, which transforms membrane potential energy into mechanical work.

PMID- 9023209
TI  - Dimerization specificity of P22 and 434 repressors is determined by multiple
      polypeptide segments.
AB  - The repressor protein of bacteriophage P22 binds to DNA as a homodimer. This
      dimerization is absolutely required for DNA binding. Dimerization is mediated by
      interactions between amino acids in the carboxyl (C)-terminal domain. We have
      constructed a plasmid, p22CT-1, which directs the overproduction of just the C
      terminal domain of the P22 repressor (P22CT-1). Addition of P22CT-1 to DNA-bound
      P22 repressor causes the dissociation of the complex. Cross-linking experiments
      show that P22CT-1 forms specific heterodimers with the intact P22 repressor
      protein, indicating that inhibition of P22 repressor DNA binding by P22CT-1 is
      mediated by the formation of DNA binding-inactive P22 repressor:P22CT-1
      heterodimers. We have taken advantage of the highly conserved amino acid
      sequences within the C-terminal domains of the P22 and 434 repressors and have
      created chimeric proteins to help identify amino acid regions required for
      dimerization specificity. Our results indicate that the dimerization specificity
      region of these proteins is concentrated in three segments of amino acid sequence
      that are spread across the C-terminal domain of each of the two phage repressors.
      We also show that the set of amino acids that forms the cooperativity interface
      of the P22 repressor may be distinct from those that form its dimer interface.
      Furthermore, cooperativity studies of the wild-type and chimeric proteins suggest
      that the location of cooperativity interface in the 434 repressor may also be
      distinct from that of its dimerization interface. Interestingly, changes in the
      dimer interface decreases the ability of the 434 repressor to discriminate
      between its wild-type binding sites, O(R)1, O(R)2, and O(R)3. Since 434 repressor
      discrimination between these sites depends in large part on the ability of this
      protein to recognize sequence-specific differences in DNA structure and
      flexibility, this result indicates that the C-terminal domain is intimately
      involved in the recognition of sequence-dependent differences in DNA structure
      and flexibility.

PMID- 9023211
TI  - Hook-length control of the export-switching machinery involves a double-locked
      gate in Salmonella typhimurium flagellar morphogenesis.
AB  - During flagellar morphogenesis in Salmonella typhimurium, the genes involved in
      filament assembly are expressed fully only after completion of hook-basal body
      assembly. This coupling of gene expression to morphogenesis is achieved by
      exporting the flagellum-specific anti-sigma factor, FlgM, out of the cell through
      the mature hook-basal body structure. Therefore, the flagellum-specific export
      apparatus must be able to sense the assembly state of the flagellar structure and
      to turn on FlgM export at a specific stage of hook assembly. It has been
      suggested that FlhB may act as the molecular switch which mediates this ordered
      export. Here, I report genetic evidence that in addition to FlhB, the product of
      a newly identified gene, rflH, is involved in the negative regulation of FlgM
      export. FlgM is released through the basal body structure lacking the hook and
      the filament only when the flhB and rflH genes are both defective. Therefore, the
      export gate for FlgM should be double locked by FlhB and RflH. The rflH gene is
      located at around 52 min, where no flagellum-related gene has been found. I
      propose a revised model of the export-switching machinery which consists of two
      systems, the hook-length signal transduction pathway and the double-locked gate
      for FlgM export.

PMID- 9023210
TI  - Identification and characterization of the dTDP-rhamnose biosynthesis and
      transfer genes of the lipopolysaccharide-related rfb locus in Leptospira
      interrogans serovar Copenhageni.
AB  - Immunity to leptospirosis is principally humorally mediated and involves
      opsonization of leptospires for phagocytosis by macrophages and neutrophils. The
      only protective antigen identified to date is the leptospiral lipopolysaccharide
      (LPS), which biochemically resembles typical gram-negative LPS but has greatly
      reduced endotoxic activity. Little is known about the structure of leptospiral
      LPS. A 2.1-kb EcoRI fragment from the chromosome of serovar Copenhageni was
      cloned in pUC18 in Escherichia coli, after which flanking regions were cloned
      from a genomic library constructed in bacteriophage lambda GEM12. Sequence
      analysis identified four open reading frames which showed similarity to the rfbC,
      rfbD, rfbB, and rfbA genes, transcribed in that order, which encode the four
      enzymes involved in the biosynthesis of dTDP-rhamnose for the assembly of LPS in
      Salmonella enterica, E. coli, and Shigella flexneri. An additional open reading
      frame downstream of the rfbCDBA locus showed similarity with the
      rhamnosyltransferase genes of Shigella and Yersinia enterocolitica but not
      Salmonella. Comparison of deduced amino acid sequences showed up to 85%
      similarity of the leptospiral proteins with those of other gram-negative
      bacteria. Polyacrylamide gel electrophoresis of recombinant clones identified the
      putative RfbCDBA proteins, while reverse transcriptase-mediated PCR analysis
      indicated that the rfbCDBA gene cluster was expressed in Leptospira. Moreover, it
      could restore normal LPS phenotype to a defined rfbB::Tn5 mutant of S. flexneri
      which was deficient in all four genes, thereby confirming the functional
      identification of a part of the leptospiral rfb locus.

PMID- 9023212
TI  - An Na+-pumping V1V0-ATPase complex in the thermophilic bacterium Clostridium
      fervidus.
AB  - Energy transduction in the anaerobic, thermophilic bacterium Clostridium fervidus
      relies exclusively on Na+ as the coupling ion. The Na+ ion gradient across the
      membrane is generated by a membrane-bound ATPase (G. Speelmans, B. Poolman, T.
      Abee, and W. N. Konings, J. Bacteriol. 176:5160-5162, 1994). The Na+-ATPase
      complex was purified to homogeneity. It migrates as a single band in native
      polyacrylamide gel electrophoresis and catalyzes Na+-stimulated ATPase activity.
      Denaturing gel electrophoresis showed that the complex consists of at least six
      different polypeptides with apparent molecular sizes of 66, 61, 51, 37, 26, and
      17 kDa. The N-terminal sequences of the 66- and 51-kDa subunits were found to be
      significantly homologous to subunits A and B, respectively, of the Na+
      translocating V-type ATPase of Enterococcus hirae. The purified V1V0 protein
      complex was reconstituted in a mixture of Escherichia coli
      phosphatidylethanolamine and egg yolk phosphatidylcholine and shown to catalyze
      the uptake of Na+ ions upon hydrolysis of ATP. Na+ transport was completely
      abolished by monensin, whereas valinomycin stimulated the uptake rate. This is
      indicative of electrogenic sodium transport. The presence of the protonophore
      SF6847 had no significant effect on the uptake, indicating that Na+ translocation
      is a primary event and in the cell is not accomplished by an H+-translocating
      pump in combination with an Na+-H+ antiporter.

PMID- 9023213
TI  - Characterization of the fimA gene encoding bundle-forming fimbriae of the plant
      pathogen Xanthomonas campestris pv. vesicatoria.
AB  - The fimA gene of Xanthomonas campestris pv. vesicatoria was identified and
      characterized. A 20-mer degenerate oligonucleotide complementary to the N
      terminal amino acid sequence of the purified 15.5-kDa fimbrillin was used to
      locate fimA on a 2.6-kb SalI fragment of the X. campestris pv. vesicatoria 3240
      genome. The nucleotide sequence of a 1.4-kb fragment containing the fimA region
      revealed two open reading frames predicting highly homologous proteins FimA and
      FimB. FimA, which was composed of 136 amino acids and had a calculated molecular
      weight of 14,302, showed high sequence identity to the type IV fimbrillin
      precursors. fimB predicted a protein product of 135 amino acids and a molecular
      weight of 13,854. The open reading frame for fimB contained near the 5' end a
      palindromic sequence with a terminator loop potential, and the expression level
      of fimB in vitro and in Xanthomonas was considerably lower than that of fimA. We
      detected an efficiently transcribed fimA-specific mRNA of 600 bases as well as
      two weakly expressed, longer mRNA species that reacted with both fimA and fimB. A
      homolog of fimA but not of fimB was detected by Southern hybridization in strains
      of X. campestris pv. vesicatoria, campestris, begoniae, translucens, and
      graminis. A fimA::omega mutant of strain 3240 was not significantly reduced in
      virulence or adhesiveness to tomato leaves. However, the fimA mutant was
      dramatically reduced in cell aggregation in laboratory cultures and on infected
      tomato leaves. The fimA mutant strain also exhibited decreased tolerance to UV
      light.

PMID- 9023214
TI  - Ti plasmid conjugation is independent of vir: reconstitution of the tra functions
      from pTiC58 as a binary system.
AB  - Two regions of the nopaline-type Ti plasmid pTiC58 are important for conjugal
      transfer of this element to recipient bacteria. These two regions were cloned
      into two independent replicons to produce a binary transfer system. For one
      region, oriT/tra, we constructed two derivatives, pFRtra and pDCtra-5. Each
      contains the oriT site and the two flanking, divergently transcribed tra operons
      that encode the DNA processing functions associated with the relaxosome. These
      two plasmids also carry traR, which encodes the transcriptional activator
      necessary for expression of transfer genes. The two plasmids differ by the
      amounts of traB sequence or sequence downstream of traG present in the construct.
      The second replicon, pPLE2, carries the traI/trb region. The traI gene confers
      production of the Agrobacterium tumefaciens N-acyl homoserine lactone
      autoinducer, while the remaining genes in the trb operon encode components of the
      mating bridge. Donors harboring the two plasmids mobilized the transfer of the
      plasmid carrying the oriT/tra region to an A. tumefaciens recipient at
      frequencies similar to that at which the intact Ti plasmid transferred. Plasmid
      pFRtra, which encodes most of traB, was mobilized at a frequency almost 10-fold
      higher than was pDCtra-5, which lacks most of the gene. A. tumefaciens donors
      also mobilized pFRtra to Escherichia coli and Pseudomonas fluorescens recipients
      at frequencies similar to those observed with A. tumefaciens recipients.
      Rhizobium meliloti harboring the binary system also transferred the oriT/tra
      component to these recipients. However, E. coli or P. fluorescens donors
      harboring the binary system did not transfer pFRtra to any of the recipients.
      Furthermore, while the A. tumefaciens and R. meliloti donors produced high levels
      of the autoinducer, the P. fluorescens and E. coli donors produced only trace
      amounts of this signal molecule. These results indicate that the tra system of
      pTiC58 is fully contained within the characterized tra and trb regions of the Ti
      plasmid, that conjugation does not require functions encoded by the vir system
      for maximal activity, and that while the Ti plasmid tra system recognizes diverse
      gram-negative bacteria as recipients, of the hosts tested, it functions only in
      members of the family Rhizobiaceae.

PMID- 9023215
TI  - Molecular characterization of glucokinase from Escherichia coli K-12.
AB  - glk, the structural gene for glucokinase of Escherichia coli, was cloned and
      sequenced. Overexpression of glk resulted in the synthesis of a cytoplasmic
      protein with a molecular weight of 35,000. The enzyme was purified, and its
      kinetic parameters were determined. Its Km values for glucose and ATP were 0.78
      and 3.76 mM, respectively. Its Vmax was 158 U/mg of protein. A chromosomal glk
      lacZ fusion was constructed and used to monitor glk expression. Under all
      conditions tested, only growth on glucose reduced the expression of glk by about
      50%. A fruR mutation slightly increased the expression of glk-lacZ, whereas the
      overexpression of plasmid-encoded fruR+ weakly decreased expression. A FruR
      consensus binding motif was found 123 bp upstream of the potential
      transcriptional start site of glk. Overexpression of glk interfered with the
      expression of the maltose system. Repression was strongest in strains that
      exhibited constitutive mal gene expression due to endogenous induction and, in
      the absence of a functional MalK protein, the ATP-hydrolyzing subunit of the
      maltose transport system. It was least effective in wild-type strains growing on
      maltose or in strains constitutive for the maltose system due to a mutation in
      malT rendering the mal gene expression independent of inducer. This demonstrates
      that free internal glucose plays an essential role in the formation of the
      endogenous inducer of the maltose system.

PMID- 9023216
TI  - Yersinia pestis LcrV forms a stable complex with LcrG and may have a secretion
      related regulatory role in the low-Ca2+ response.
AB  - Yersinia pestis contains a virulence plasmid, pCD1, that encodes many virulence
      associated traits, such as the Yops (Yersinia outer proteins) and the
      bifunctional LcrV, which has both regulatory and antihost functions. In addition
      to LcrV and the Yops, pCD1 encodes a type III secretion system that is
      responsible for Yop and LcrV secretion. The Yop-LcrV secretion mechanism is
      believed to regulate transcription of lcrV and yop operons indirectly by
      controlling the intracellular concentration of a secreted repressor. The activity
      of the secretion mechanism and consequently the expression of LcrV and Yops are
      negatively regulated in response to environmental conditions such as Ca2+
      concentration by LcrE and, additionally, by LcrG, both of which have been
      proposed to block the secretion mechanism. This block is removed by the absence
      of Ca2+ or by contact with eukaryotic cells, and some Yops are then translocated
      into the cells. Regulation of LcrV and Yop expression also is positively affected
      by LcrV. Previously, LcrG was shown to be secreted from bacterial cells when the
      growth medium lacks added Ca2+, although most of the LcrG remains cell
      associated. In the present study, we showed that the cell-associated LcrG is
      cytoplasmically localized. We demonstrated that LcrG interacts with LcrV to form
      a heterodimeric complex by using chemical cross-linking and copurification of
      LcrG and LcrV. Additionally, we found that small amounts of LcrV and YopE can be
      detected in periplasmic fractions isolated by cold osmotic shock and spheroplast
      formation, indicating that their secretion pathway is accessible to the periplasm
      or to these procedures for obtaining periplasmic fractions. We propose that the
      cytoplasmically localized LcrG blocks the Yop secretion apparatus from the
      cytoplasmic side and that LcrV is required to remove the LcrG secretion block to
      yield full induction of Yop and LcrV secretion and expression.

PMID- 9023217
TI  - Cloning and functional analysis of the P97 swine cilium adhesin gene of
      Mycoplasma hyopneumoniae.
AB  - Colonization of the swine respiratory tract by Mycoplasma hyopneumoniae is
      accomplished by specific binding to the cilia of the mucosal epithelial cells.
      Previous studies have implicated a 97-kDa outer membrane-associated protein, P97,
      that appeared to mediate this interaction. In order to further define the role of
      P97 in adherence to porcine cilia, the structural gene was cloned and sequenced,
      and the recombinant products were analyzed. Monoclonal antibodies were used to
      identify recombinant clones in a genomic library expressed in an opal suppressor
      host because of alternate codon usage by mycoplasmas. The gene coding for P97 was
      then identified by Tn1000 mutagenesis of recombinant clones. DNA sequence
      analysis revealed an open reading frame coding for a 124.9-kDa protein with a
      hydrophobic transmembrane spanning domain. The N-terminal sequence of purified
      P97 mapped at amino acid position 195 of the translated sequence, indicating that
      a processing event had occurred in M. hyopneumoniae. Both recombinant P97 protein
      expressed in an Escherichia coli opal suppressor host and M. hyopneumoniae bound
      specifically to swine cilia, and the binding was inhibited by heparin and
      fucoidan, thus supporting the hypothesis that P97 was actively involved in
      binding to swine cilia in vivo.

PMID- 9023218
TI  - Translation of the mRNA for the sporulation gene spoIIID of Bacillus subtilis is
      dependent upon translation of a small upstream open reading frame.
AB  - We report the existence of a small open reading frame (usd) that is located
      between the promoter and coding sequence for the sporulation gene spoIIID in
      Bacillus subtilis. The mRNA from the usd-spoIIID operon contains an inverted
      repeat sequence that is predicted to form a stem-loop structure that would
      sequester the ribosome binding site for spoIIID. A mutation eliminating the
      ribosome binding site for the upstream open reading frame caused an
      oligosporogenous phenotype and interfered with the translation, but not the
      transcription, of the downstream gene spoIIID. We propose that efficient
      synthesis of SpoIIID requires that the putative stem-loop structure be disrupted
      by translation through the upstream open reading frame.

PMID- 9023219
TI  - Expression, inducer spectrum, domain structure, and function of MopR, the
      regulator of phenol degradation in Acinetobacter calcoaceticus NCIB8250.
AB  - Degradation of phenol by Acinetobacter calcoaceticus NCIB8250 involves (sigma54
      dependent expression of a multicomponent phenol hydroxylase and catechol 1,2
      dioxygenase encoded by the mop operon. Complementation of a new mutant deficient
      in phenol utilization yielded the regulatory locus mopR. It is located in
      divergent orientation next to the mop operon. MopR is constitutively expressed at
      a low level from a sigma70-type promoter and belongs to the NtrC family of
      regulators. The amino acid sequence is similar to that of XylR regulating xylene
      degradation and to that of DmpR regulating dimethylphenol degradation in
      Pseudomonas spp. However, it shows a different effector profile for substituted
      phenols than DmpR. MopR activates phenol hydroxylase expression in the presence
      of phenol in Escherichia coli, indicating that it binds the effector. The phenol
      binding A domains of MopR and DmpR have fewer identical residues than the A
      domains of DmpR and XylR, despite the fact that XylR recognizes different
      effectors. This suggests that sequence conservation in the A domain does not
      reflect the potential to bind the respective effectors. Overexpression of the
      MopR A domain in the presence of wild-type MopR causes loss of mop inducibility
      by phenol, establishing its negative transdominance over MopR. Deletion of 110
      residues from the N terminus did not affect transdominance of the truncated
      domain, whereas deletion of 150 residues abolished it completely. This result
      establishes the distinction of two subdomains, A(N) and A(C), which together
      constitute the A domain. The C-terminal portion of the A domain, A(C), shows
      considerable affinity for the C domain, even in the presence of the trigger
      phenol.

PMID- 9023220
TI  - MalFGK complex assembly and transport and regulatory characteristics of MalK
      insertion mutants.
AB  - MalK is a peripheral cytoplasmic membrane protein that has multiple activities in
      Escherichia coli. It associates with integral cytoplasmic membrane proteins MalF
      and MalG to form the maltose transport complex (MalFGK), a member of the ATP
      binding cassette (ABC) superfamily of proteins. In addition, MalK participates in
      two different regulatory pathways which modulate mal gene expression and MalFGK
      transport activity. We have created a set of malK mutations for analysis of the
      protein's structure and folding. These mutations, distributed throughout malK,
      are all similar insertions of 31 codons. The ability of each mutant to function
      in maltose transport and MalK-dependent regulation was characterized.
      Furthermore, we have exploited a sensitive biochemical assay to classify our MalK
      insertion mutants into two additional categories: MalFGK complex assembly
      proficient and complex assembly defective. The regions containing the insertions
      in the assembly-proficient class should correspond to areas within MalK that are
      surface exposed within the MalFGK complex. Affected regions in assembly-deficient
      mutants may be involved in critical structural contacts within the complex. One
      mutant apparently blocks assembly at an intermediate stage prior to
      oligomerization of the final MalFGK complex. This work contributes to the
      analysis of ABC transport proteins and to the study of the assembly process for
      hetero-oligomeric membrane proteins.

PMID- 9023221
TI  - The terminal quinol oxidase of the hyperthermophilic archaeon Acidianus
      ambivalens exhibits a novel subunit structure and gene organization.
AB  - A terminal quinol oxidase has been isolated from the plasma membrane of the
      crenarchaeon Acidianus ambivalens (DSM 3772) (formerly Desulfurolobus
      ambivalens), cloned, and sequenced. The detergent-solubilized complex oxidizes
      caldariella quinol at high rates and is completely inhibited by cyanide and by
      quinolone analogs, potent inhibitors of quinol oxidases. It is composed of at
      least five different subunits of 64.9, 38, 20.4, 18.8, and 7.2 kDa; their genes
      are located in two different operons. doxB, the gene for subunit I, is located
      together with doxC and two additional small open reading frames (doxE and doxF)
      in an operon with a complex transcription pattern. Two other genes of the oxidase
      complex (doxD and doxA) are located in a different operon and are cotranscribed
      into a common 1.2-kb mRNA. Both operons exist in duplicate on the genome of A.
      ambivalens. Only subunit I exhibits clear homology to other members of the
      superfamily of respiratory heme-copper oxidases; however, it reveals 14
      transmembrane helices. In contrast, the composition of the accessory proteins is
      highly unusual; none is homologous to any known accessory protein of cytochrome
      oxidases, nor do homologs exist in the databases. DoxA is classified as a subunit
      II equivalent only by analogy of molecular size and hydrophobicity pattern to
      corresponding polypeptides of other oxidases. Multiple alignments and
      phylogenetic analysis of the heme-bearing subunit I (DoxB) locate this oxidase at
      the bottom of the phylogenetic tree, in the branch of heme-copper oxidases
      recently suggested to be incapable of superstoichiometric proton pumping. This
      finding is corroborated by lack of the essential amino acid residues delineating
      the putative H+-pumping channel. It is therefore concluded that A. ambivalens
      copes with its strongly acidic environment simply by an extreme turnover of its
      terminal oxidase, generating a proton gradient only by chemical charge
      separation.

PMID- 9023223
TI  - Nitrogenase activity and regeneration of the cellular ATP pool in Azotobacter
      vinelandii adapted to different oxygen concentrations.
AB  - The in vivo activity of nitrogenase under aerobiosis was studied with
      diazotrophic chemostat cultures of Azotobacter vinelandii grown under glucose- or
      phosphate-limited conditions at different dilution rates (Ds, representing the
      growth rate mu) and different dissolved oxygen concentrations. Under steady-state
      conditions, the concentration as well as the cellular level of ATP increased in
      glucose-limited cultures when D was increased. Irrespective of the type of growth
      limitation or the dissolved oxygen concentration, the steady-state concentrations
      of ATP and of dinitrogen fixed by nitrogenase increased in direct proportion to
      each other. Specific rates of dinitrogen fixation as well as of the regeneration
      of the cellular ATP pool were compared with specific rates of cellular
      respiration. With glucose-limited cultures, the rate of regeneration of the ATP
      pool and the rate of respiration varied in direct proportion to each other. This
      relationship, however, was dependent on the dissolved oxygen concentration. As
      compared to the phosphate-sufficient control, phosphate-limited cultures
      exhibited the same nitrogenase activity but significantly increased respiratory
      activities. Rates of ATP regeneration and of cellular respiration of phosphate
      limited cultures did not fit into the relationship characteristic of glucose
      limited cultures. However, a linear relationship between the rates of dinitrogen
      fixation and ATP regeneration was identified irrespective of the type of growth
      limitation and the dissolved oxygen concentration. The results suggest that the
      ATP supply rather than cellular oxygen consumption is of primary importance in
      keeping nitrogenase activity in aerobic cultures of A. vinelandii.

PMID- 9023222
TI  - Characterization of the rcsB gene from Erwinia amylovora and its influence on
      exoploysaccharide synthesis and virulence of the fire blight pathogen.
AB  - RcsB belongs to a family of positive regulators of exopolysaccharide synthesis in
      various enterobacteria. The rcsB gene of the fire blight pathogen Erwinia
      amylovora was cloned by PCR amplification with consensus primers, and its role in
      exopolysaccharide (EPS) synthesis was investigated. Its overexpression from high
      copy-number plasmids stimulated the synthesis of the acidic EPS amylovoran and
      suppressed expression of the levan-forming enzyme levansucrase. Inactivation of
      rcsB by site-directed mutagenesis created mutants that were deficient in
      amylovoran synthesis and avirulent on host plants. In addition, a cosmid which
      complemented rcsB mutants was selected from a genomic library. The spontaneous E.
      amylovora mutant E8 has a similar phenotype and was complemented by the cloned
      rcsB gene. The rcsB region of strain E8 was also amplified by PCR, and the
      mutation was characterized as a nine-nucleotide deletion at the start of the rcsB
      gene. Nucleotide sequence analysis of the E. amylovora rcsB region and the
      predicted amino acid sequence of RcsB revealed extensive homology to rcsB and the
      encoded protein of other bacteria such as Escherichia coli and Erwinia stewartii.
      In all three organisms, rcsB is localized adjacent to the rcsC gene, which is
      transcribed in the opposite direction of rcsB. The E. amylovora rcsB gene has now
      been shown to strongly affect the formation of disease symptoms of a plant
      pathogen.

PMID- 9023224
TI  - Investigation of ribosome binding by the Shiga toxin A1 subunit, using
      competition and site-directed mutagenesis.
AB  - The enzymatic subunit of Shiga toxin (StxA1) is a member of the ribosome
      inactivating protein (RIP) family, which includes the ricin A chain as well as
      other examples of plant toxins. StxA1 catalytically depurinates a well-conserved
      GAGA tetra-loop of 28S rRNA which lies in the acceptor site of eukaryotic
      ribosomes. The specific activities of native StxA1, as well as mutated forms of
      the enzyme with substitutions in catalytic site residues, were measured by an in
      vitro translation assay. Electroporation was developed as an alternative method
      for the delivery of purified A1 polypeptides into Vero cells. Site-directed
      mutagenesis coupled with N-bromosuccinimide modification indicated that the sole
      tryptophan residue of StxA1 is required for binding it to the 28S rRNA backbone.
      Northern analysis established that the catalytic site substitutions reduced
      enzymatic activity by specifically interfering with the capacity of StxA1 to
      depurinate 28S rRNA. Ribosomes were protected from StxA1 by molar excesses of
      tRNA and free adenine, indicating that RIPs have the capacity to enter the
      acceptor site groove prior to binding and depurinating the GAGA tetra-loop.

PMID- 9023225
TI  - The 32-kilobase exp gene cluster of Rhizobium meliloti directing the biosynthesis
      of galactoglucan: genetic organization and properties of the encoded gene
      products.
AB  - Proteins directing the biosynthesis of galactoglucan (exopolysaccharide II) in
      Rhizobium meliloti Rm2011 are encoded by the exp genes. Sequence analysis of a 32
      kb DNA fragment of megaplasmid 2 containing the exp gene cluster identified
      previously (J. Glazebrook and G. C. Walker, Cell 56:661-672, 1989) revealed the
      presence of 25 open reading frames. Homologies of the deduced exp gene products
      to proteins of known function suggested that the exp genes encoded four proteins
      involved in the biosynthesis of dTDP-glucose and dTDP-rhamnose, six
      glycosyltransferases, an ABC transporter complex homologous to the subfamily of
      peptide and protein export complexes, and a protein homologous to Rhizobium NodO
      proteins. In addition, homologies of three Exp proteins to transcriptional
      regulators, methyltransferases, and periplasmic binding proteins were found. The
      positions of 26 Tn5 insertions in the exp gene cluster were determined, thus
      allowing the previously described genetic map to be correlated with the sequence.
      Operon analysis revealed that the exp gene cluster consists of five
      complementation groups. In comparison to the wild-type background, all exp
      complementation groups were transcribed at a substantially elevated level in the
      regulatory mucR mutant.

PMID- 9023226
TI  - Purification and preliminary characterization of (E)-3-(2,4-dioxo-6-methyl-5
      pyrimidinyl)acrylic acid synthase, an enzyme involved in biosynthesis of the
      antitumor agent sparsomycin.
AB  - Sparsomycin is an antitumor antibiotic produced by Streptomyces sparsogenes.
      Biosynthetic experiments have previously demonstrated that one component of
      sparsomycin is derived from L-tryptophan via the intermediacy of (E)-3-(4-oxo-6
      methyl-5-pyrimidinyl)acrylic acid and (E)-3-(2,4-dioxo-6-methyl-5
      pyrimidinyl)acrylic acid. An enzyme which catalyzes the conversion of (E)-3-(4
      oxo-6-methyl-5-pyrimidinyl)acrylic acid to (E)-3-(2,4-dioxo-6-methyl-5
      pyrimidinyl)acrylic acid has been purified 740-fold to homogeneity from S.
      sparsogenes. The molecular mass of the native and denatured enzyme was 87 kDa,
      indicating that the native enzyme is monomeric. The enzyme required NAD+ for
      activity but lacked rigid substrate specificity, since analogs of both NAD+ and 3
      (4-oxo-6-methyl-5-pyrimidinyl)acrylic acid could serve as substrates. The enzyme
      was very weakly inhibited by mycophenolic acid. Monovalent cations were required
      for activity, with potassium ions being the most effective. The enzyme exhibited
      sensitivity toward diethylpyrocarbonate and some thiol-directed reagents, and it
      was irreversibly inhibited by 6-chloropurine. The properties of the enzyme
      suggest it is mechanistically related to inosine-5'-monophosphate dehydrogenase.

PMID- 9023227
TI  - Replication and segregation of a miniF plasmid during the division cycle of
      Escherichia coli.
AB  - Replication of the miniF plasmid pML31 was examined during the division cycle of
      Escherichia coli growing with doubling times between 40 and 90 min at 37 degrees
      C and compared to the replication of plasmid pBR322 and the minichromosome pAL70.
      The replication pattern of pML31 was indistinguishable from that of pBR322 at all
      growth rates and very different from the cell-cycle-specific replication of the
      minichromosome. It is concluded that both pML31 and pBR322 plasmids can replicate
      at all stages of the division cycle, with a probability of replication that
      increases gradually, but perhaps not exponentially, during the cycle. In
      contrast, the modes of segregation of pML31 and pBR322 plasmids into daughter
      cells at division appeared to differ, raising the possibility that pML31 may
      segregate in a nonrandom fashion similar to that of chromosomes and
      minichromosomes.

PMID- 9023228
TI  - Evidence that KpsT, the ATP-binding component of an ATP-binding cassette
      transporter, is exposed to the periplasm and associates with polymer during
      translocation of the polysialic acid capsule of Escherichia coli K1.
AB  - KpsT utilizes ATP to effect translocation of the polysialic acid capsule of
      Escherichia coli K1. We have previously proposed a mechanistic model for the
      action of this protein. Here, we provide evidence to support two predictions of
      the model: that KpsT associates with polymer and that KpsT is accessible from the
      periplasmic surface of the inner membrane.

PMID- 9023229
TI  - Identification of the epitope for a highly cross-reactive monoclonal antibody on
      the major sigma factor of bacterial RNA polymerase.
AB  - A highly cross-reactive monoclonal antibody (MAb), 2G10, was found to react in a
      conserved region of Escherichia coli RNA polymerase sigma70. The epitope was
      localized to amino acids 470 to 486, which included part of conserved region 3.1.
      The epitope for MAb 3D3, a MAb which maps close to the 2G10 epitope, was also
      determined.

PMID- 9023230
TI  - Plasmid virulence gene expression induced by short-chain fatty acids in
      Salmonella dublin: identification of rpoS-dependent and rpo-S-independent
      mechanisms.
AB  - The Salmonella plasmid virulence spvABCD genes are growth phase regulated and
      require RpoS for maximal expression in stationary phase. We identified a growth
      phase-independent expression of spv which is mediated by short-chain fatty acids.
      During this fatty acid-mediated expression of spv, RpoS is required for induction
      only during exponential phase. In stationary phase, an rpoS-independent mechanism
      is responsible for expression of spv.

PMID- 9023231
TI  - Role of His243 in the phosphatase activity of EnvZ in Escherichia coli.
AB  - EnvZ undergoes autophosphorylation at His243 and subsequently transfers the
      phosphate group to OmpR. EnvZ also possesses an OmpR-phosphate phosphatase
      activity. We examined the role of His243 in the phosphatase function by replacing
      His with either Val, Tyr, Ser, Asp, or Asn. EnvZH243V and EnvZH243Y were both
      shown to possess phosphatase activity in vitro. In addition, the mutant proteins
      were able to reduce the high level of OmpR-phosphate present in the envZ473
      strain. These results indicate that His243 of EnvZ is not essential for
      stimulating the dephosphorylation of OmpR-phosphate.

PMID- 9023232
TI  - Two cistrons of the gerC operon of Bacillus subtilis encode the two subunits of
      heptaprenyl diphosphate synthase.
AB  - The two proteins (GerC1 and GerC3) encoded by the gerC locus of Bacillus
      subtilis, which has been shown to be involved in vegetative cell growth and spore
      germination, were identified as dissociable heterodimers of the heptaprenyl
      diphosphate synthase involved in the biosynthesis of the side chain of
      menaquinone-7.

PMID- 9023233
TI  - The inactivated plasmid inititator protein RepC/RepC* may have a regulatory role.
AB  - During replication of the plasmid pT181, the initiator protein RepC is modified
      by the addition of an oligodeoxynucleotide, giving rise to a new form, RepC*.
      Here we show that during in vitro replication, RepC* is radioactively labeled,
      suggesting that the source of the RepC* oligodeoxynucleotide is the newly
      synthesized pT181 DNA. The RepC/RepC* heterodimer retains its ability to bind the
      pT181 double-strand origin and, therefore, it may act as a competitive inhibitor
      of the RepC homodimer during replication.

PMID- 9023235
TI  - Turn angle and run time distributions characterize swimming behavior for
      Pseudomonas putida.
AB  - The swimming behavior of Pseudomonas putida was analyzed with a tracking
      microscope to quantify its run time and turn angle distributions. Monte Carlo
      computer simulations illustrated that the bimodal turn angle distribution of P.
      putida reduced collisions with obstacles in porous media in comparison to the
      unimodal distribution of Escherichia coli.

PMID- 9023236
TI  - The development of otolaryngic allergy in the United States.

PMID- 9023234
TI  - bmr3, a third multidrug transporter gene of Bacillus subtilis.
AB  - A third multidrug transporter gene named bmr3 was cloned from Bacillus subtilis.
      Although Bmr3 shows relatively low homology to Bmr and Blt, the substrate
      specificities of these three transporters overlap. Northern hybridization
      analysis showed that expression of the bmr3 gene was dependent on the growth
      phase.

PMID- 9023237
TI  - Davis et al.: "Modification of cochlear potentials produced by streptomycin
      poisoning and extensive venous obstruction." (Laryngoscope 1958;68:596-627).

PMID- 9023238
TI  - Ketorolac tromethamine and hemorrhage in tonsillectomy: a prospective,
      randomized, double-blind study.
AB  - Ketorolac tromethamine (KT) is a nonsteroidal, antiinflammatory analgesic. Its
      nonsedating property makes it an attractive analgesic for sleep apnea patients
      undergoing uvulopharyngopalatoplasty, but its antiplatelet activity makes the
      potential for postoperative hemorrhage a concern. A prospective, randomized,
      double-blind study was designed to evaluate the bleeding risk of KT using adult
      tonsillectomy patients as the model. Patients were randomized into two groups
      receiving Meperidine (MP) (controls) or KT for the first postoperative day.
      Posttonsillectomy bleeding rates of 7% (3/43) in the MP group and 18.9% (7/37) in
      the KT group were demonstrated, but this difference was not statistically
      significant. The number of KT doses administered had no effect on the incidence
      of bleeding or the number of cases requiring return to the operative suite for
      hemostasis. Although this study did not attain statistical significance, the
      trend towards increased hemorrhage with KT is worrisome. This study and other
      reports in the literature support the manufacturer's warning that the use of KT
      is contraindicated in major surgery.

PMID- 9023239
TI  - Computed tomography and magnetic resonance diagnosis of allergic fungal
      sinusitis.
AB  - The objective of this study was to describe CT and MR findings in patients with
      allergic fungal sinusitis (AFS). CT and MR images were examined from 10 patients
      with histologically proven AFS. All patients demonstrated CT evidence of central
      sinus high attenuation and T2-weighted MR signal void corresponding to surgically
      proven areas of thick inspissated allergic mucin. AFS is a distinct clinical
      entity with a highly specific radiographic appearance based on CT and MRI.

PMID- 9023240
TI  - Autologous fat injection into the vocal folds: technical considerations and long
      term follow-up.
AB  - Numerous materials have been used over the years for vocal fold augmentation.
      Early use of bioreactive compounds, such as paraffin, gave way to relatively
      inert substances, such as Teflon. More recently biocompatible materials, such as
      collagen and autologous fat, have gained wider acceptance. Autologous fat, in
      particular, is an easily obtainable source for potential rehabilitation of
      scarred, paralytic, and atrophic vocal folds. However, long-term systematic
      follow-up has been lacking. Since 1991 we at the University of Kansas Center for
      Voice and Swallowing Disorders have employed autologous fat for vocal fold
      augmentation, primarily for either paralysis or repair of a volume-deficient
      vocal fold segment. Twenty-two patients have completed > or = 1 year of follow-up
      studies, including graded video-laryngostroboscopy, electroglottography,
      computerized acoustic analysis, and blinded perceptual analysis by two speech
      language pathologists. Statistically significant improvement was demonstrated in
      many parameters tested, frequently improving with time. Although the volume
      deficient group had more "normal" values, the paralysis group had greater
      improvement in many variables using fat injection. We conclude that while
      autologous fat injections of the vocal fold may have long-term benefits, certain
      technical considerations and criteria of selection of patients are critical for
      success.

PMID- 9023241
TI  - Time course of recovery after Epley maneuvers for benign paroxysmal positional
      vertigo.
AB  - The canalith repositioning maneuver (CRP) of Epley is an effective treatment for
      benign paroxysmal positional vertigo (BPPV). While CRP has been advocated by some
      as a "single treatment" for BPPV, others have had less uniform results for this
      self-limited disorder. In order to better define the role of CRP in relieving
      vertigo, we studied the time course of recovery in 27 consecutive cases of BPPV.
      We recorded nystagmus after each head maneuver and at each evaluation until
      complete resolution took place, using absence of nystagmus as a strict criterion
      for cure. We found that while 93% of patients improved, many had persistent
      nystagmus at the first evaluation, and in only 63% was resolution clearly related
      to a CRP session. We believe that in certain cases, the effect of CRP may be due
      to adaptive conditioning, rather than particle redistribution.

PMID- 9023242
TI  - Reliability of disposable intraoperative facial nerve stimulators.
AB  - Facial nerve injury is one major morbidity of surgery performed along the course
      of this nerve. Surgeons frequently employ stimulators to identify and protect the
      nerve. Both disposable devices as well as larger, reusable stimulators are
      available. Despite their common use, relatively little documentation exists
      regarding the safety and reliability of these devices. We tested the electrical
      output of the four disposable, single-use motor nerve stimulators that are
      marketed in the United States. We found that each produced consistent stimulus
      output over time. One stimulator slightly exceeded the manufacturer's listed
      output while three devices produced significantly less voltage and current than
      specified by the manufacturer.

PMID- 9023243
TI  - Myringotomized mice develop myringosclerosis in the pars flaccida and not in the
      pars tensa.
AB  - The development of myringosclerosis has been correlated with increased production
      of oxygen-derived free radicals. For the present study, we used a null mutant
      mouse lacking extracellular superoxide dismutase to test the hypothesis that
      increased production of free radicals can cause the development of
      myringosclerosis. Null mutant mice and wild-type, control mice were
      myringotomized and kept in ambient air for 3 weeks. Both groups developed
      myringosclerosis in the pars flaccida, but not in the pars tensa. The sclerotic
      lesions were visible in both the light and the electron microscope but not in the
      otomicroscope. In particular, the localization of the sclerotic deposits was
      found beneath both the inner and outer epidermal epithelium. No difference
      concerning the extent or number of sclerotic lesions between the null mutant and
      the wild-type mice could be distinguished.

PMID- 9023244
TI  - Hydrogen peroxide in acute otitis media in guinea pigs.
AB  - Evidence has emerged that oxygen free radicals contribute to middle-ear mucosa
      damage in acute otitis media (AOM). Streptococcus pneumoniae is the most common
      pathogen in AOM and produces hydrogen peroxide, a free radical intermediate, as
      it grows. To better characterize the mechanism of free radical damage in AOM, an
      experiment was conducted to examine the production of hydrogen peroxide. Thirty
      two guinea pigs were injected transtympanically with bacteria in the left
      (infected) middle ear and sterile saline into the right (control) middle ear.
      Middle-ear fluid was removed and analyzed for quantity of hydrogen peroxide.
      Results indicated significantly greater hydrogen peroxide levels in infected
      versus control middle-ear fluid at 6, 12, and 24 h. Likely sources of hydrogen
      peroxide include both the neutrophil response to infection and pneumococcal
      growth and death.

PMID- 9023245
TI  - Demonstration of autoantibodies to the endolymphatic sac in Meniere's disease.
AB  - Recent evidence suggests that immune mechanisms may underlie some cases of
      Meniere's disease. This study was conducted to determine whether an autoimmune
      mechanism is involved. Sera from 30 patients with Meniere's disease were reacted
      with human endolymphatic sacs and examined by indirect immunohistochemistry and
      fluorescence microscopy. Three of the samples (10%) showed positive staining,
      indicating immunoglobulin G (IgG) binding against the sac. No positive staining
      occurred when sera from healthy individuals or phosphate-buffered saline was used
      as a control. Clinical data showed an association between immunoreactivity and
      extent of disease (worse hearing over a shorter disease course and bilateral
      involvement). This study suggests that, in some cases of Meniere's disease,
      autoantibodies directed against human endolymphatic sac are present in the sera,
      supporting the theory that a specific autoimmune reaction takes place in a
      minority of patients with Meniere's disease.

PMID- 9023246
TI  - Differential expression of transthyretin in papillary tumors of the endolymphatic
      sac and choroid plexus.
AB  - Aggressive papillary tumors of the temporal bone, occurring sporadically or as
      part of von Hippel-Lindau disease, have been shown to originate within the
      endolymphatic sac or duct. Also implicated as a potential precursor from which
      some of these tumors may arise is ectopic choroid plexus epithelium. To aid in
      the differentiation between papillary tumors of endolymphatic sac and duct origin
      and those arising from choroid plexus, an immunohistochemical study using stains
      for transthyretin (TTR), cytokeratins, S-100 protein, epithelial membrane antigen
      (EMA), and glial fibrillary acidic protein (GFAP) was carried out on archival
      specimens of normal and neoplastic endolymphatic sac and duct and choroid plexus
      epithelium. Transthyretin, a marker for choroid plexus epithelium, was found to
      show differential expression between choroid plexus papillomas and aggressive
      papillary tumors of the endolymphatic sac or duct. Therefore the use of TTR in
      concert with other immunohistochemical stains appear to aid in the
      differentiation between intracranial and intratemporal papillary tumors arising
      from choroid plexus and endolymphatic sac or duct epithelium.

PMID- 9023247
TI  - Comparison of anti-heat shock protein 70 (anti-hsp70) and anti-68-kDa inner ear
      protein in the sera of patients with Meniere's disease.
AB  - The 68-kDa antigen detected in the sera of patients with autoimmune inner ear
      disease is known to represent the highly inducible heat shock protein 70 (hsp70).
      To evaluate the existence of anti-hsp70 in the sera of patients with Meniere's
      disease and to develop a more reliable method to detect this antibody, the sera
      of patients and controls were examined. Bovine kidney (MDBK) cells were cultured
      and some of them were heat shocked. Proteins in the cells were separated using
      sodium dodecyl sulfate polyacrylamide gel electrophoresis. Sera were reacted
      simultaneously with the blots of non-heat-shocked cells and heat-shocked cells.
      The serum was considered positive if the band in the 70-kDa location was denser
      in the lane with heat-shocked cells relative to non-heat-shocked cells. Presence
      of the antibody against the 68-kDa protein was compared with the result of
      immunoblotting with MDBK cells. In immunoblotting with MDBK cells, 33.3% of
      patients with Meniere's disease had anti-hsp70, while in the control group, only
      5% had this antibody. Of the 60 cases, 13 were positive against both hsp70 and
      the 68-kDa protein, whereas 7 were positive only against hsp70 and 6 only against
      the 68-kDa protein. These differences appeared to result from the greater
      sensitivity of the differential anti-hsp assay and from difficulties in
      interpreting the results in blots with bovine inner ear extracts because of
      faint, broad, or overlapping multiple bands. Quite a number of patients with
      Meniere's disease have anti-hsp70, and it may be indicative of an immune etiology
      of the disease. The Western blot using heat-shocked and non-heat-shocked cells
      could be a reliable method to detect this antibody.

PMID- 9023248
TI  - Localization of inducible heat shock protein mRNA in the guinea pig cochlea with
      a nonradioactive in situ hybridization technique.
AB  - Cell types of the guinea pig cochlea that contain mRNA of the inducible heat
      shock protein (HSP72) were determined with an in situ hybridization technique,
      using a biotinylated oligonucleotide probe. Staining was present in the spiral
      limbus, spiral prominence, stria vascularis, and organ of Corti (supporting,
      pillar, outer hair, and interdental cells). In sections digested with pepsin,
      only spiral ganglion cells stained. The pattern of staining was similar in normal
      and heat-stressed animals. Therefore, HSP72 mRNA is present in many guinea pig
      cochlear cell types, some of which have not previously been shown to contain
      HSP72 protein. Differences in HSP72 mRNA and protein staining may be attributable
      to stress or processing techniques, but they may also suggest mechanisms unique
      to guinea pigs and primates, who normally express the inducible form of HSP.

PMID- 9023249
TI  - In situ hybridization for Aspergillus and Penicillium in allergic fungal
      sinusitis: a rapid means of speciating fungal pathogens in tissues.
AB  - Allergic fungal sinusitis (AFS) is a serious form of sinonasal fungal disease
      that is commonly associated with Aspergillus or Dematiaceous fungi. This study
      was performed to determine the incidence of Aspergillus or Penicillium in AFS by
      using in situ hybridization (ISH) for Aspergillus and Penicillium ribosomal RNA
      (rRNA). The Fontana-Masson melanin stain (FMMS) was also used to detect pigmented
      fungi (A. niger and Dematiaceous fungi). ISH was performed on 26 patients: 17 AFS
      cases with histologic evidence of fungi, 5 AFS cases without histologic evidence
      of fungi, 3 cases of invasive fungal sinusitis (IFS), and 1 case of fungus ball.
      Nine AFS specimens with histologic evidence of fungi were ISH positive.
      Positivity was also noted in two of three IFS cases, while no staining was seen
      in the fungus ball and in six AFS specimens without fungi demonstrable by silver
      stains. Six ISH-positive cases were FMMS positive, suggesting A. niger. Five ISH
      negative AFS specimens were FMMS positive, suggesting Dematiaceous fungi. In
      summary, many AFS patients in our institution demonstrate Aspergillus/Penicillium
      organisms. Ancillary techniques may help identify fungi responsible for AFS if
      cultures are negative or not performed. ISH for rRNA is a useful means for
      rapidly speciating fungi in human tissues.

PMID- 9023250
TI  - Clinical classification as a guide to treatment of sinusitis in children.
AB  - Evaluation of all 153 children undergoing CT scan of the paranasal sinuses for
      recalcitrant sinusitis symptoms between January 1988 and July 1992 was performed.
      Clinical categorization into groups of patients presenting with chronic sinusitis
      (CS) and recurrent acute sinusitis (RAS) was based upon pattern of disease and
      presentation. Clinical symptoms and signs, radiological examination, treatment,
      and outcome were compared between these distinct clinical groups. Eighty-two
      (55%) children were categorized as RAS and 68 (45%) as CS. Children with CS
      presented more frequently with a persistent cough, purulent nasal discharge,
      immune deficiency, and more severe mucosal disease on CT than children with RAS.
      Medical therapy successfully controlled the symptoms of sinusitis in 79 (96%)
      with RAS versus 27 (40%) with CS. Surgery was performed in 44 children: 3 (3.6%)
      with RAS versus 41 (60%) with CS, p < 0.01. At a mean follow-up of 2.0 years,
      >80% of all the children were either asymptomatic or improved regardless of
      treatment modality. These data support the use of clinical classification as a
      guide to medical versus surgical therapy in children with sinusitis.

PMID- 9023251
TI  - One-stage reconstruction of partial laryngopharyngeal defects.
AB  - Advanced-stage lesions of the hypopharynx or tongue base often involve the
      larynx. The difficulty of reconstructing large partial laryngopharyngeal defects
      can result in total laryngectomy being performed to avoid the assumed problems
      with aspiration. This article describes the first reported experience using the
      pectoralis musculocutaneous flap for primary one-stage reconstruction of
      laryngopharyngeal defects following resection of advanced-stage lesions, to
      reconstruct both the laryngeal and the pharyngeal components of the defect. In
      this group of 21 patients, there were 16 with hypopharyngeal and 5 with tongue
      base cancers. Two had received prior treatment, and all received some form of
      postoperative radiotherapy and/or chemotherapy. Six patients experienced
      complications, including two fistulae, three wound infections, two myocardial
      infarctions, and one colon perforation. There were no instances of stenosis of
      the reconstructed segment. The length of hospitalization ranged from 9 to 60
      days, the average being 17 days. Forty-seven percent (21) of the patients were
      not tolerating an oral diet at the time of discharge. However, 15 patients (71%)
      ultimately were eating by mouth, with 13 (62%) achieving an oral intake of
      liquids and solids. This analysis supports the hypothesis that the pectoralis
      major musculocutaneous flap is an effective one-stage primary reconstruction
      technique for laryngopharyngeal defects in patients either who have received
      prior therapy or who will receive postoperative therapy.

PMID- 9023252
TI  - Prognostic features in tall cell papillary carcinoma and insular thyroid
      carcinoma.
AB  - Tall cell papillary carcinoma (TCPC) and insular carcinoma (IC) are variants of
      thyroid carcinoma that are considered to be more aggressive than well
      differentiated papillary or follicular carcinoma. To determine the clinical
      significance of these diagnoses, we evaluated 65 patients with these tumors.
      There were 30 TCPCs, 27 ICs, and 8 ICs or TCPCs with focal anaplastic carcinoma
      (FAC). Forty-two patients (27 TCPCs, 14 ICs, and 1 FAC) are alive and free of
      disease. Nine patients with IC are alive with distant metastases. Ten patients (2
      TCPCs, 2 ICs, and 7 FACs) died of disease. Univariate analysis of disease-free
      interval determined that, as for all thyroid carcinomas, patient age, tumor size,
      extrathyroidal extension, and lymph node metastases were significant for
      prognosis. ICs did significantly worse than TCPCs. Focal anaplastic
      dedifferentiation predicted a worse prognosis. Multivariate analysis for disease
      free interval showed age, number of lymph node metastases, and tumor type to be
      significant. Analysis of the same factors for prediction of mortality showed that
      TCPC and IC were not significantly different. These data suggest that TCPC is
      less aggressive than IC, which often results in disseminated disease. Focal AC
      predicts poor survival.

PMID- 9023253
TI  - Endoscopic CO2 laser excision of large or recurrent laryngeal saccular cysts in
      adults.
AB  - Saccular cysts are uncommon disorders that represent cystic dilatation of the
      laryngeal saccule. They are distinguished from laryngoceles by their lack of
      lumenal continuity with the endolarynx, and the fact that they are not air
      filled. Voice change is the most common clinical presentation in adults, whereas
      airway compromise is more common in infants. Management recommendations range
      from observation of asymptomatic lesions, to endoscopic marsupialization or
      excision, to excision through a laryngotomy or the thyrohyoid membrane. The
      literature states that large or recurrent saccular cysts require the exposure
      afforded by a transcervical approach. This report describes complete endoscopic
      laser excision of large, symptomatic saccular cysts in seven adults. Four of the
      seven patients were referred with recurrent cysts after the failure of endoscopic
      marsupialization procedures. None required tracheotomy, and only three of seven
      were observed overnight in the hospital. Surgical technique with emphasis on
      complete excision, pre- and postoperative radiographic and surgical anatomy, and
      treatment outcome are discussed.

PMID- 9023254
TI  - Quantitative evaluation of the effects of thyroarytenoid muscle activity upon
      pliability of vocal fold mucosa in an in vivo canine model.
AB  - Stiffness of the vocal fold is a significant factor in determining mucosal wave
      propagation and in the control of the fundamental frequency of phonation. We
      measured pliability of the vocal fold mucosa in an in vivo canine model as an
      index of stiffness while the histological layer-by-layer structure of the vocal
      fold was not disrupted. The point 1 mm below the free edge showed a maximal
      pliability that gradually diminished toward the tracheal side and reached a
      minimum. When the thyroarytenoid (TA) muscle contracted, pliability of the mucosa
      was significantly increased (P < 0.001). Mucosal pliability of the excised larynx
      was significantly increased compared with that in vivo (P < 0.001). The point of
      minimal pliability in the absence of TA muscle contraction did not shift after
      excision of the larynx, while TA muscle contraction caused a downward shift of
      the point of minimal pliability. Mucosal pliability can thus be used to
      quantitatively assess the effects of TA muscle contraction on stiffness of the
      vocal fold mucosa.

PMID- 9023255
TI  - Kikuchi's disease: report of three cases and an overview.
AB  - We describe, to our knowledge, the first native Finnish patients with Kikuchi's
      histiocytic necrotizing lymphadenitis. The diagnosis was based in all cases on
      histopathological findings in open biopsy. The disease was first detected in
      Japan in 1972, but in Scandinavia, until this decade, there had been no cases
      reported. Our patients were young, otherwise healthy women who had cervical
      lymphadenopathy, fever, and fatigue as their main symptoms. In two of them, the
      disease was mild and subsided spontaneously within 2-6 months. One patient with
      more fulminant lymphadenopathy was treated with antimicrobial and
      antiinflammatory drugs. She became symptomless in 3 months. The cause of
      Kikuchi's disease is unknown. A viral or postviral hyperimmune reaction has been
      proposed as its etiology. Malignant lymphoma and systemic lupus erythematosus are
      differential diagnoses. Histopathological findings are pathognomonic and
      pathologists must be aware of its typical characteristics.

PMID- 9023256
TI  - Tubeless laryngotracheal surgery in infants and children via jet ventilation
      laryngoscope.
AB  - We present the first use of tubeless superimposed combined high- and low
      frequency jet ventilation (SHFJV) with a jet laryngoscope in laryngotracheal
      surgery in infants and children. Twenty-eight patients underwent 53 operative
      procedures. The average age of the patients was 7.3 years. The most common
      diagnoses were laryngeal papillomatosis and subglottic stenosis. The duration of
      jet ventilation averaged 33 min. The gas exchange was sufficient in each case.
      The advantages of SHFJV in the surgery of the laryngotracheal area in infants and
      children are optimal view at the larynx and trachea, maximum space for the
      handling, application of the laser without risks, no time limitation, suitability
      for stenosis, and neither anesthetic nor surgical complications.

PMID- 9023257
TI  - Endoscopic repair of type IA laryngeal clefts.

PMID- 9023258
TI  - Platysma myocutaneous flap reconstruction.

PMID- 9023259
TI  - Direct block of voltage-sensitive sodium channels by genistein, a tyrosine kinase
      inhibitor.
AB  - Genistein, an isoflavone inhibitor of tyrosine-specific protein kinases, was
      shown to specifically block the 22Na+ influx through voltage-sensitive Na+
      channels in cultured rat brain neurons, whereas other tyrosine kinase antagonists
      such as lavendustin A, compound 5, tyrphostin A47 and an erbstatin analog were
      inactive at concentrations known to block kinase activity in other neuronal
      systems. Dose-response curves for genistein indicated a half-maximum effect at 60
      microM. Daidzein, an inactive analog of genistein, had a similar inhibitory
      effect on the 22Na+ influx with a half-maximum effect at 195 microM. The time
      course of genistein action was rapid, because maximum effect on 22Na+ influx was
      obtained in less than 20 s at 100 microM. Analysis of Na+ currents by the whole
      cell recording technique showed that 20 microM genistein reduced the sodium
      current and shifted the voltage dependence of both activation and inactivation
      curves. No competition with [3H]saxitoxin binding was observed, whereas the
      binding of [3H]batrachotoxinin A 20-alpha-benzoate to rat brain synaptosomal
      membranes was partially inhibited, which suggested a direct or allosteric
      interaction with neurotoxin binding site 2. These data taken together clearly
      indicate that the inhibition of voltage-sensitive sodium channels by genistein is
      not mediated by tyrosine kinase inhibition.

PMID- 9023260
TI  - Acetaldehyde as well as ethanol is metabolized by human CYP2E1.
AB  - Acetaldehyde was oxidized by rat and human hepatic microsomes in the presence of
      NADPH. We designated this NADPH-dependent oxidation system MAOS (microsomal
      acetaldehyde-oxidizing system), to distinguish it from the NAD-dependent
      acetaldehyde oxidation system of acetaldehyde dehydrogenase in mitochondria and
      cytosol. This activity was increased 2.3-fold by giving rats ethanol. Judging
      from the Vmax/Km values, the metabolic capacity of rat hepatic microsomes for
      MAOS activity was increased 24-fold by ethanol. The acetaldehyde oxidation
      activity of eight forms of purified rat cytochrome P450 was investigated in a
      reconstituted system. CYP2E1 had the highest level, followed by CYP1A2 and 4A2.
      Immunoinhibition studies showed that an anti-CYP2E1 antibody inhibited 90% of the
      MAOS activity in rats given ethanol. NADPH-dependent acetate formation was 12% or
      33.6% of the NAD-dependent acetate formation in liver homogenates of control rats
      and those treated with ethanol, respectively. We investigated human MAOS activity
      further. Among the 10 forms of human cytochrome P450 expressed in yeast, CYP2E1
      had especially high acetaldehyde oxidation activity. The correlation of MAOS
      activity with the levels of immunoreactive CYP2E1 in individual human microsomes
      was highly significant (r2 = 0.88, P < .01). These results indicate that hepatic
      CYP2E1 mainly contributes to MAOS in rats and humans, the pathway of which may
      play an alternative role against acetaldehyde in the liver after alcohol
      consumption together with acetaldehyde dehydrogenase in the metabolism of
      acetaldehyde.

PMID- 9023261
TI  - Adenosine A1 receptor blockade does not abolish the cardioprotective effects of
      the adenosine triphosphate-sensitive potassium channel opener bimakalim.
AB  - There has been controversy regarding whether ATP-sensitive potassium channel
      activation protects hearts through adenosine A1 receptor activation or the
      converse. We addressed this issue by determining the effect of the adenosine A1
      receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) on the
      cardioprotective activity of the ATP-sensitive potassium channel opener
      bimakalim. In isolated rat hearts subjected to 25 min of global ischemia and 30
      min of reperfusion, bimakalim significantly reduced lactate dehydrogenase release
      and improved postischemic recovery of contractile function. Bimakalim increased
      the time to the onset of ischemic contracture (EC25 = 1.2 microM), compared with
      vehicle, and 10 microM DPCPX had no effect on this protective action (EC25 = 1.1
      microM). The 10 microM concentration of DPCPX was sufficient to abolish the
      bradycardic and cardioprotective effects of the adenosine A1 receptor agonist (R)
      (-)-N6-(2-phenylisopropyl)adenosine. DPCPX alone had no effect on the severity of
      ischemia/reperfusion damage. Glyburide completely abolished the cardioprotective
      effects of bimakalim. Bimakalim (1 microg/kg, intracoronarily) given over four
      periods of 5 min, interspersed with 10-min drug-free periods, before a 60-min
      occlusion and 3-hr reperfusion significantly reduced infarction size in
      anesthetized dogs (25 +/- 5 and 8 +/- 2% of the left ventricular area at risk for
      vehicle- and bimakalim-treated groups, respectively). DPCPX had no effect on the
      infarction-sparing activity of bimakalim (9 +/- 3% of the left ventricular area
      at risk). The protective effect of bimakalim was not accompanied by marked
      hemodynamic changes or by changes in regional myocardial blood flow. The results
      of this study suggest that the cardioprotective effects of ATP-sensitive
      potassium channel openers are not dependent on adenosine A1 receptor activation
      in rat or dog models of ischemia.

PMID- 9023262
TI  - The reinforcing and discriminative stimulus effects of the novel cocaine analog
      2beta-propanoyl-3beta-(4-tolyl)-tropane in rhesus monkeys.
AB  - 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT), is a cocaine analog that inhibits
      dopamine uptake, binding with high affinity and selectivity to the dopamine
      transporter. In the present study, the behavioral effects of PTT were evaluated
      in two models of cocaine abuse: drug self-administration and drug discrimination.
      In the first experiment, rhesus monkeys (n = 3) were trained to self-administer
      cocaine (0.03 and 0.1 mg/kg/injection, i.v.) under a fixed-interval 5-min
      schedule. Presession administration of PTT (0.03-0.3 mg/kg, i.v.) or cocaine (0.3
      3.0 mg/kg, i.v.) were evaluated. At both self-administered doses of cocaine, PTT
      decreased response rates and total session intakes and was approximately 0.5 to
      1.0 log units more potent than cocaine. In experiment 2, the reinforcing effects
      of PTT (0.003-0.1 mg/kg/injection) were evaluated in a separate group of monkeys
      (n = 4) responding under a fixed-interval 5-min schedule of cocaine (0.03
      mg/kg/injection) presentation. When substituted for cocaine, PTT maintained
      response rates similar to saline-maintained rates and significantly lower than
      rates maintained by cocaine (0.003-0.3 mg/kg/injection). Total session PTT intake
      was significantly lower than cocaine intake. In experiment 3, the discriminative
      stimulus effects of PTT (0.003-0.1 mg/kg, i.m.) were evaluated in monkeys (n = 3)
      trained to discriminate cocaine (0.2 mg/kg, i.m.) from saline (0.5 ml). PTT
      substituted for cocaine in a dose-dependent manner and was 0.5 to 1.0 log units
      more potent than cocaine. At the highest PTT dose, cocaine-appropriate responding
      was observed 8 to 24 hr after the injection. These results demonstrated that the
      long-acting indirect dopamine agonist PTT was effective in decreasing cocaine
      self-administration and in abuse liability testing showed a unique behavioral
      profile, not functioning as a reinforcer when substituted for cocaine and
      producing discriminative stimulus effects similar to cocaine.

PMID- 9023263
TI  - Quantitative evaluation of brain distribution and blood-brain barrier efflux
      transport of probenecid in rats by microdialysis: possible involvement of the
      monocarboxylic acid transport system.
AB  - This study was performed to evaluate quantitatively the brain distribution and
      the efflux transport across the blood-brain barrier of probenecid, using in vivo
      microdialysis and in situ brain perfusion techniques. The brain interstitial
      fluid (ISF)-to-plasma cerebrospinal fluid (CSF)-to-plasma and brain tissue-to
      plasma unbound concentration ratios of probenecid at steady state were less than
      unity, which suggests restricted distribution in the brain. An uphill
      concentration gradient from ISF to plasma and a downhill concentration gradient
      from CSF to ISF were observed. Kinetic analysis revealed that the efflux
      clearance from brain ISF to plasma (0.0373 ml/min/g brain) was significantly
      greater than the influx clearance from plasma to brain (0.00733 ml/min/g brain).
      The ratio of the ISF concentration (Cisf) to the plasma unbound concentration
      (Cp,f) of probenecid was increased 2- to 3-fold by salicylate (3.7 mM) and
      benzoate (3.6 mM), which are accepted as substrates of the monocarboxylic acid
      transport system, compared with the same ratio for the control. In addition, the
      ratio Cisf/Cp,f was increased by treatment with N-ethylmaleimide, a sulfhydryl
      modifying agent, whereas p-aminohippuric acid and choline did not produce
      increasing effects on Cisf/Cp,f. These data suggest that the restricted
      distribution of probenecid in the brain may be ascribed to efficient efflux from
      the brain ISF, which may be regulated by the monocarboxylic acid transport system
      at a relatively high ISF concentration.

PMID- 9023264
TI  - Dopamine receptor subtypes: differential regulation after 8 months treatment with
      antipsychotic drugs.
AB  - Regulation of dopamine receptor subtypes was determined after long-term (8 mo)
      administration of typical and atypical antipsychotic drugs using 3H-nemonapride,
      3H-raclopride, 3H-spiperone, 3H-7-hydroxy-N,N-di-n-propyl-2-aminotetralin, 3H
      SCH23390 and 125I-sulpiride in vitro receptor autoradiography. Drug-induced
      receptor upregulation was remarkably different across the various D2-like
      receptor radioligands. Chronic haloperidol treatment resulted in a strong
      increase in 3H-nemonapride, 3H-spiperone and 125I-sulpiride binding to striatal
      areas, whereas 3H-raclopride binding was marginally affected. Raclopride
      treatment elevated striatal binding of 3H-nemonapride and 3H-spiperone to a
      lesser extent, and did not alter 3H-raclopride binding. Clozapine treatment did
      not affect the binding of the tritiated radioligands. These differences suggest
      that 3H-nemonapride and 3H-spiperone are binding to an additional subset of D2
      like receptors, not recognized by 3H-raclopride. 3H-Nemonapride binding in the
      presence of 300 nM raclopride uncovered a striatal binding site (designated as D4
      like receptor), that was up-regulated after chronic haloperidol, raclopride and
      clozapine treatment. The 125I-sulpiride binding sites in the prefrontal cortex
      were also up-regulated by the three antipsychotics. In contrast, 3H-spiperone
      binding sites were down-regulated in the prefrontal and dorsolateral cortical
      area. Chronic antipsychotic treatment did not affect Dl-like or D3 dopamine
      receptor subtype binding.

PMID- 9023265
TI  - Adenosine triphosphate attenuates renal sympathetic nerve activity through left
      ventricular chemosensitive receptors.
AB  - We previously reported that ATP, but not adenosine, administered i.v. attenuates
      the baroreflex-mediated increase in sympathetic nerve activity in response to
      arterial hypotension by a vagal afferent mechanism. It was not elucidated in that
      study which vagal afferent endings are involved. Mongrel dogs were anesthetized
      with alpha-chloralose, thoracotomy was performed and a 27-gauge hypodermic needle
      was inserted into the left circumflex coronary artery. The left renal sympathetic
      nerves were isolated and placed on a bipolar silver electrode for measurement of
      renal sympathetic nerve activity (RSNA). Dose-response effects of intracoronary
      or i.v. infusion of ATP (100, 200 or 400 microg/kg/min) on RSNA and mean arterial
      pressure were studied in neuraxis-intact and cervically vagotomized dogs. RSNA
      was increased dose-dependently with decreasing mean arterial pressure during the
      i.v. ATP infusion. Elevation of RSNA was attenuated by higher intracoronary ATP
      infusion rates, despite the fact that mean arterial pressure was decreased dose
      dependently. Left ventricular end-diastolic pressure, however, remained
      unchanged. This suppression of RSNA by the intracoronary ATP infusion was
      completely abolished by bilateral cervical vagotomy. Our data suggest that ATP
      attenuates reflex increases in sympathetic nerve activity by possibly stimulating
      ventricular chemoreceptors with cardiac vagal afferents.

PMID- 9023266
TI  - High-affinity agonist binding is not sufficient for agonist efficacy at 5
      hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex
      model.
AB  - In this study, the relationship between high-affinity agonist binding and second
      messenger production was examined at native and mutant 5-hydroxytryptamine2A
      receptors. At native 5-hydroxytryptamine2A receptors all agonists, with the
      exception of quipazine, discriminated between high- and low-affinity states of
      the receptor, as determined by analysis of competition binding assays. There was
      no correlation between the ability of selected agonists to label the high
      affinity agonist state and to augment phosphoinositide hydrolysis. Quipazine,
      which did not discriminate between the affinity states of the receptor, behaved
      as a full agonist. Similar results were obtained when a point mutation (F340L) of
      a highly conserved phenylalanine located in transmembrane domain VI was examined.
      With the F340L mutant, most of the agonists tested labeled significantly fewer
      high-affinity sites, compared with the native receptor. There was no significant
      relationship between high-affinity agonist binding and second messenger
      production. Bufotenine and 4-iodo-3,5-dimethoxyphenylisopropylamine labeled
      similar percentages of high-affinity agonist binding sites (22% vs. 26%), but 4
      iodo-3,5-dimethoxyphenylisopropylamine behaved as a full agonist, whereas
      bufotenine was devoid of detectable agonist activity. The inability of selected
      agonists to activate phosphoinositide hydrolysis was not due solely to lower
      agonist affinity for the mutant receptor, because the binding affinity of
      quipazine was unchanged by the F340L mutation but quipazine had no detectable
      agonist activity at the mutant receptor. Our results demonstrate that the ability
      of an agonist to promote the high-affinity state of the 5-hydroxytryptamine2A
      receptor is not correlated with its ability to augment second messenger
      production. These results are consistent with recent models of G protein-receptor
      functioning (e.g., modified ternary complex model) that predict that additional
      transition states of the receptor-ligand complex are essential for agonist
      efficacy.

PMID- 9023267
TI  - Characterization of haloperidol and trifluperidol as subtype-selective N-methyl-D
      aspartate (NMDA) receptor antagonists using [3H]TCP and [3H]ifenprodil binding in
      rat brain membranes.
AB  - [3H]TCP and [3H]ifenprodil binding to N-methyl-D-aspartate (NMDA) receptors in
      rat forebrain membranes was used to compare the inhibition of haloperidol and
      trifluperidol with that of ifenprodil and eliprodil. In the [3H]TCP binding
      assay, inhibition curves of ifenprodil, eliprodil, haloperidol and trifluperidol
      revealed two affinity states in the presence of glutamate, glycine and
      spermidine. The potency of these agents to inhibit the high-affinity fraction of
      the binding agreed with the results of other studies investigating their potency
      to block glutamate-induced current at recombinant NR1a/NR2B NMDA receptors
      expressed in Xenopus oocytes. These agents also inhibited [3H]ifenprodil binding
      in a biphasic manner, whether in the absence or the presence of either the sigma
      site ligand GBR-12909 or spermidine. Spermidine reduced the fraction of high
      affinity sites labeled with [3H]ifenprodil. The only alteration in the affinity
      was a decrease in the IC50 value of haloperidol to inhibit the high-affinity
      fraction of [3H]ifenprodil binding. GBR-12909 also reduced the fraction of
      [3H]ifenprodil sites inhibited by these compounds with high affinity, with no
      change in the affinity for either fraction. These data suggest that spermidine is
      neither a competitive antagonist at the fraction of the binding inhibited by
      these agents with high affinity, nor is this fraction of the binding to sigma
      sites. Haloperidol and trifluperidol represent a new class of agent that
      interacts at a site that is labeled by [3H]ifenprodil as well as [3H]TCP in rat
      brain membranes and that closely reflects ifenprodil's voltage-independent site
      on the recombinant NR1a/NR2B subtype of the NMDA receptor.

PMID- 9023268
TI  - Evidence that tolerance and dependence of guinea pig myenteric neurons to opioids
      is a function of altered electrogenic sodium-potassium pumping.
AB  - Ouabain acutely depolarizes most types of cells through inhibition of
      electrogenic Na+,K+ pumping and is a useful tool with which to study conditions
      that affect electrogenic pumping. Intracellular recording techniques were used
      with neurons of the guinea pig myenteric plexus/longitudinal muscle preparation
      exposed to ouabain. Of 35 S neurons exposed to ouabain (1 microM), 15 were
      hyperpolarized by 10 +/- 2 mV, 11 were depolarized by 8 +/- 2 mV and the
      remaining neurons had no change in membrane potential. The nonselective potassium
      channel antagonist tetraethylammonium chloride (TEA; 0.5 mM) alone evoked modest
      (<5 mV) and inconsistent changes in the resting membrane potential of S neurons.
      However, in the presence of TEA, the hyperpolarizing response to 1 microM ouabain
      was eliminated, and the proportion of cells depolarized by ouabain increased from
      31% to 83%. Glibenclamide (10 microM) and 100 nM iberiotoxin did not change the
      pattern of membrane potential changes induced by 1 microM ouabain. Calcium-free
      buffer eliminated the hyperpolarization and potentiated the depolarization
      induced by 1 microM ouabain. Ouabain (5 microM), in either the presence or
      absence of TEA, induced depolarization in all neurons tested (mean, 15-16 mV),
      indicating a predominant effect of inhibition of electrogenic pumping. These data
      suggest that ouabain may directly or indirectly activate myenteric S neuron
      calcium-sensitive potassium channels as well as inhibit the Na+,K+ pump and that
      TEA will antagonize the former effect. Chronic exposure (morphine pellets) of
      guinea pigs to morphine resulted in a partial depolarized state of myenteric
      neurons, as previously reported. Ouabain (5 microM), either with or without TEA,
      depolarized neurons from chronically morphine-treated guinea pigs very little (5
      6 mV) in comparison with naive neurons (15-16 mV). This supports the conclusion
      that the depolarized state of morphine-tolerant neurons is associated with a
      reduction in electrogenic Na+,K+ pumping.

PMID- 9023269
TI  - Delta-1 opioid receptor-mediated antinociceptive properties of a nonpeptidic
      delta opioid receptor agonist, (-)TAN-67, in the mouse spinal cord.
AB  - The effects of enantiomorphs of TAN-67 (2-methyl-4a alpha-(3-hydroxyphenyl)
      1,2,3,4,4a,5,12,12a alpha-octahydro-quinolino[2,3,3-g]isoquinoline), (-)TAN-67
      and (+)TAN-67, given intrathecally (i.t.) on antinociceptive response with the
      tail-flick test were studied in male ICR mice. (-)TAN-67 at doses from 17.9 to
      89.4 nmol given i.t. produced a dose- and time-dependent inhibition of the tail
      flick response, whereas its enantiomer (+)TAN-67 even at smaller doses (1.8, 4.5
      and 8.9 nmol) given i.t. decreased the latencies of the tail-flick response. In
      addition, (+)TAN-67 at higher doses (17.9-89.4 nmol) given i.t. produced
      scratching and biting pain-like responses. The antinociceptive response induced
      by i.t.-administered (-)TAN-67 was mediated by the stimulation of delta-1 but not
      by delta-2, mu or kappa opioid receptors, because the effect was blocked by the
      i.t. pretreatment with BNTX, but not by naltriben, [D-Phe-Cys-Tyr-[D-Try-Orn-Thr
      Pen-Thr-NH2 or nor-binaltorphimine dihydrochloride. Pretreatment with (-)TAN-67
      given i.t. 3 hr earlier attenuated the tail-flick inhibition induced by
      subsequent i.t. administration of (-)TAN-67 and by [D-Pen2,5]enkephalin (DPDPE).
      However, the tail-flick inhibition induced by [D-Ala2]deltorphin II, [D
      Ala2,NMePhe4,Gly5-ol]enkephalin and U50,488H were not affected by (-)TAN-67
      pretreatment. Conversely, pretreatment with DPDPE given i.t. 3 hr earlier
      attenuated the tail-flick inhibition induced by subsequent i.t. administration of
      (-)TAN-67 and by DPDPE. However, the tail-flick inhibition induced by [D
      Ala2]deltorphin II was not affected by i.t. DPDPE pretreatment. It is concluded
      that (-)TAN-67 given i.t. produces delta-1 opioid receptor-mediated
      antinociception; on the other hand, its enantiomer (+)TAN-67 produces
      hyperalgesia. Present studies provide other evidence that delta-1 opioid
      receptors exist separated from delta-2 opioid receptor.

PMID- 9023270
TI  - Differential inhibition of murine prostaglandin synthase-1 and -2 by nonsteroidal
      anti-inflammatory drugs using exogenous and endogenous sources of arachidonic
      acid.
AB  - Mouse embryonic fibroblasts (10T1/2) and Chinese hamster ovary (AS52) cell lines
      that stably express murine prostaglandin G/H synthase (PGHS)-1 or -2 were used to
      compare the effects of exogenous and endogenous arachidonic acid (AA) on isozyme
      selective inhibition by acetylsalicylic acid, indomethacin, and N-[2
      cyclohexyloxyl-4-nitrophenyl] methanesulfonamide (NS-398). The rationale for
      developing in vitro systems that identify PGHS-2-selective inhibitors is the
      belief that inhibition of this isoform accounts for the therapeutic benefits of
      nonsteroidal anti-inflammatory drugs (NSAIDs). Conversely, inhibition of PGHS-1
      is believed to cause the toxic effects of NSAIDs, such as gastric and renal
      damage. When exogenous AA was used, acetylsalicylic acid was a 5- to 10-fold more
      potent inhibitor of PGHS-1, whereas indomethacin was a 4- to 5-fold more potent
      inhibitor of PGHS-2. Within the dose range tested (1 x 10(-6) microM to 100
      microM), NS-398 was highly selective for PGHS-2. When calcium ionophore A23187
      was used to mobilize endogenous AA, acetylsalicylic acid and indomethacin
      equipotently inhibited both PGHS-1 and PGHS-2 isozymes. NS-398 remained highly
      selective for PGHS-2 in 10T1/2 and AS52 cells but also effectively (100%)
      inhibited PGHS-1 in AS52 cells. Pharmacological data derived using endogenous AA
      correlated better with the anti-inflammatory efficacy of these NSAIDs in
      laboratory animals and with the therapeutic/toxic activities of these NSAIDs in
      rheumatoid arthritic patients. Therefore, screening for PGHS-selective NSAIDs may
      best be conducted in intact cells that express high levels of each isozyme using
      endogenous sources of AA.

PMID- 9023271
TI  - NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel
      blocker pharmacology.
AB  - The potencies of various N-methyl-D-aspartate(NMDA) receptor channel blockers
      were determined at recombinant NMDA receptors containing differing combinations
      of NR1 and NR2 subunits expressed in Xenopus laevis oocytes. When the NR1 subunit
      was varied (NR1e/NR2A or NR1b/NR2A), none of the 9 channel blockers tested
      displayed a statistically different affinity. In contrast, altering NR2
      composition changed the affinities of several channel blockers. Three of 10
      compounds displayed significantly higher affinities for NR1b/NR2C receptors than
      NR1b/NR2A receptors, and three of five compounds had higher affinity at NR1b/NR2C
      than NR1b/NR2B receptors. Both MK-801 and N-[1-(2-thienyl)cyclohyxyl]piperidine
      displayed identical affinities at all receptor subunit combinations tested.
      However, these two compounds displayed significantly slower rates of blockade and
      unblockade at NR1b/NR2C than at NR1b/NR2A receptors, perhaps reflecting the
      shorter mean open times of NR1/NR2C receptors. NR1b/NR2B and NR1b/NR2A were
      distinguished by one of five compounds tested. Taken together, these results
      indicate that NR2 subunits impart differing pharmacological profiles to NMDA
      receptors; thus, it may be possible to develop NMDA receptor channel blocker
      antagonists of greater subtype selectivity.

PMID- 9023272
TI  - The phosphodiesterase type 4 (PDE4) inhibitor CP-80,633 elevates plasma cyclic
      AMP levels and decreases tumor necrosis factor-alpha (TNFalpha) production in
      mice: effect of adrenalectomy.
AB  - Rolipram was previously reported to elevate plasma cyclic adenosine 3',5'
      monophosphate (cAMP) and inhibit serum tumor necrosis factor-alpha (TNF-alpha)
      production in mice. CP-80,633, a new cyclic nucleotide phosphodiesterase (PDE4)
      inhibitor, has been shown to augment intracellular cAMP levels and to inhibit
      TNFalpha release from human monocytes in vitro. This study was undertaken to
      determine the effect of p.o. CP-80,633 on plasma cAMP levels and
      lipopolysaccharide-induced TNFalpha production in mice with and without adrenal
      glands. CP-80,633 dose-dependently (3-32 mg/kg p.o.) elevated plasma cAMP levels
      and decreased systemic TNFalpha production in response to i.p. injection of
      lipopolysaccharide. Elevated plasma cAMP levels can be detected for up to 4 hr.
      CP-80,633 (10 mg/kg p.o.) caused a 6-fold increase in the plasma cAMP level, a 2
      fold increase in the plasma epinephrine level and a greater than 95% reduction in
      TNFalpha production. Unlike CP-80,633, neither vinpocetine, dipyridamole, SKB
      94,120 nor zaprinast, at 100 mg/kg p.o., modified the cAMP response, which
      suggests that this response is mediated by inhibition of PDE4. Adrenalectomy
      reduced the cAMP response and completely blocked the epinephrine response;
      however, the levels of plasma cAMP in the CP-80,633-treated mice (10 mg/kg p.o.)
      remained elevated (vehicle: 47.3 +/- 6.8 vs. CP-80,633: 98.4 +/- 10.3 pmol/ml, n
      = 7, P < .05). This effect is mimicked by treatment of control mice with
      propranolol, which demonstrates that beta adrenoreceptors contribute to the cAMP
      response. Removal of adrenal glands significantly increased the LPS-induced
      elevation of serum TNFalpha. The ability of CP-80,633 to block the TNFalpha
      response was only slightly affected by adrenalectomy (ED50 = 1.2 mg/kg in
      controls vs. 3.9 mg/kg in adrenalectomized mice). Taken together, these results
      show that CP-80,633, when given p.o. to mice, is capable of elevating plasma cAMP
      and inhibiting TNFalpha production and that adrenal catecholamines contribute
      significantly to the effect of CP-80,633 on the cAMP response but only slightly
      to its effect on the systemic TNFalpha response.

PMID- 9023273
TI  - Aging and drug interactions. III. Individual and combined effects of cimetidine
      and cimetidine and ciprofloxacin on theophylline metabolism in healthy male and
      female nonsmokers.
AB  - The individual and combined effects of cimetidine and ciprofloxacin on
      theophylline metabolism were examined in healthy young and elderly male and
      female nonsmokers. Single-dose studies of theophylline pharmacokinetics were
      performed at base line and on the fifth day of each of three treatment regimens
      consisting of 400 mg cimetidine every 12 hr, 500 mg ciprofloxacin every 12 hr and
      the combination of cimetidine and ciprofloxacin. Base-line theophylline plasma
      clearance and formation clearance of theophylline metabolites decreased with age
      in both gender groups to a similar extent (20% less in elderly men than in young
      men; 24% less in elderly women than in young women). Individually, cimetidine and
      ciprofloxacin produced proportionate declines in plasma theophylline clearance
      that were similar among the four groups (range, 23.4-32.7% decrease). The
      combined regimen yielded further impairment in theophylline elimination compared
      with each agent alone (range, 35.9-42.6% decrease). Cimetidine was a nonselective
      inhibitor of theophylline metabolic pathways in young men, but it exerted a
      greater inhibitory effect on N-demethylation pathways in the other groups.
      Ciprofloxacin inhibited N-demethylations of theophylline to a greater extent than
      the hydroxylation pathway. Coadministration of these two inhibitors further
      reduced the formation of theophylline metabolites. The proportionate reduction in
      formation clearance of theophylline metabolites was similar among the four
      groups. Thus, the response to inhibition of theophylline metabolism by cimetidine
      and ciprofloxacin is not influenced by age or gender.

PMID- 9023274
TI  - Cisplatin-induced nephrotoxicity in porcine proximal tubular cells: mitochondrial
      dysfunction by inhibition of complexes I to IV of the respiratory chain.
AB  - Cisplatin-induced nephrotoxicity was studied in porcine proximal tubular cells,
      focusing on the relationship between mitochondrial damage, reactive oxygen
      species (ROS) and cell death. Cisplatin specifically affected mitochondrial
      functions: complexes I to IV of the respiratory chain were inhibited 15 to 55%
      after 20 min of incubation with 50 to 500 microM, respectively. As a result,
      intracellular ATP was decreased to 70%. The mitochondrial glutathione (reduced
      form) (GSH)-regenerating enzyme GSH-reductase (GSH-Rd) activity was reduced by
      20%, which contributed to a 70% reduction of GSH levels and ROS formation. The
      residual electron flow through the mitochondrial respiratory chain was the source
      of ROS because additional inhibition of the complexes I to IV reduced ROS
      formation. Because cisplatin affects both GSH-Rd and complexes I to IV, cells
      were incubated with N,N'-bis(2-chloroethyl)-N-nitrosourea (inhibitor of GSH-Rd)
      and inhibitors of the different complexes. Only N,N'-bis(2-chloroethyl)-N
      nitrosourea with rotenone (complex I inhibitor) induced ROS formation, which
      indicates that inhibition of complex I and inhibition of the GSH-Rd is probably
      the cause of ROS formation. However, the resulting ROS is not the cause of cell
      death because diphenyl-p-phenylene-diamine and deferoxamine, which completely
      prevented ROS, could not prevent cell death. Similarly, the antioxidants did not
      completely prevent the decrease in activity of complexes I to IV, ATP or GSH
      levels. In conclusion, ROS formation does occur during cisplatin-induced
      toxicity, but it is not the direct cause of cell death.

PMID- 9023275
TI  - Positive feedback modulation of acetylcholine release from isolated rat superior
      cervical ganglion.
AB  - The effects of selective nicotinic acetylcholine (ACh) receptor (nAChR) agonists
      and antagonists on the stimulation-evoked release of [3H]ACh were studied in rat
      isolated superior cervical ganglion loaded with [3H]choline and superfused in a 2
      ml chamber. Nicotine and 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), but not
      cytisine, increased the stimulation (2 Hz)-evoked release of [3H]ACh in a
      concentration-dependent manner. The rank order of potency to increase stimulation
      evoked release for the nAChR agonists (nicotine > DMPP >> cytisine) suggests that
      the beta4 subunit of nAChRs is not involved in the release. The finding that
      alpha-bungarotoxin was effective in preventing the effect of DMPP and itself
      significantly reduced the release indicates that the alpha7 subunit is located
      presynaptically and may be involved in the positive feedback modulation.
      Hexamethonium inhibited the effect of DMPP with an apparent dissociation constant
      (Kd) of 11.5 +/- 1.5 microM. Hexamethonium and other nAChR antagonists, i.e., (+)
      tubocurarine (100 microM), mecamylamine (3 microM), dihydro-beta-erythroidine (3
      microM), pancuronium (10 microM) and alpha-bungarotoxin (2 microM), also
      decreased the stimulation-evoked release of [3H]ACh. The effect of hexamethonium
      was independent of stimulation frequency (2, 10 and 30 Hz) applied. Atropine
      enhanced the stimulation-evoked release of ACh, indicating that there is negative
      feedback modulation of ACh release associated with neuronal activity. In
      contrast, when the nicotinic positive feedback was prevented by hexamethonium,
      atropine failed to enhance the release. These findings indicate that muscarinic
      receptor-mediated inhibition of ACh release functions in cases in which the
      release is enhanced by ACh via stimulation of presynaptic nAChRs. A similar
      interaction was found between A1 receptor-mediated reduction and nAChR-mediated
      positive feedback modulation of [3H]ACh release. The results suggest the presence
      of positive feedback modulation of ACh release via presynaptic nAChRs in rat
      superior cervical ganglion.

PMID- 9023276
TI  - Morphine tolerance and dependence in the rat intestine in vivo.
AB  - There has been no previous demonstration of opioid tolerance and dependence with
      respect to the propulsive and contractile activities of the gut in vivo. In the
      experiments described herein, morphine was administered continuously (1 mg/kg/hr
      s.c., 72 hr) and/or by bolus injection (2 mg/kg) and intestinal motility and
      transit were evaluated in unanesthetized rats. Tolerance in intestinal motility
      (contractions) and propulsion (transit) was measured in two ways, i.e., by
      measuring the time required for motility and propulsion to return to control
      values and by measuring the loss of effectiveness of bolus morphine administered
      to animals receiving continuous infusion of the opiate. The dose of morphine
      chosen for continuous administration (1 mg/kg/hr s.c. via Alzet minipumps) was
      based on the dose at which morphine inhibited intestinal propulsion by 50%.
      Morphine (1 mg/kg/hr) decreased the frequency of contractions in, and propulsion
      along, the small bowel and colon and produced mild antinociception. The frequency
      of duodenal and colonic contractions returned to normal within 13 to 16 hr. After
      24 hr of morphine treatment, the inhibitory effects of bolus doses of morphine on
      motility and transit were diminished; the effects were eventually lost (48 hr).
      Similarly, the antinociceptive effects of bolus doses of morphine were diminished
      by 18 hr and lost by 24 hr. Naloxone (0.1 mg/kg s.c.) given to morphine-tolerant
      animals (72 hr) resulted in an increase in the frequency and amplitude of
      contractions in the colon, an increase in the propulsive activity of the small
      intestine and colon and diarrhea. These results provide direct demonstration of
      opioid tolerance and dependence of contractile and propulsive activity in the rat
      intestine in vivo.

PMID- 9023278
TI  - Active transport of nitrofurantoin across a mouse mammary epithelial monolayer.
AB  - The antibiotic nitrofurantoin is transported against an electrochemical gradient
      into milk. A monolayer of CIT3 cells, a subline of the Comma 1D normal mouse
      mammary epithelial cell line, transports [14C]-nitrofurantoin against a
      concentration gradient from the basal to the apical solution when grown on
      membrane filters. In a side-by-side diffusion chamber with well-stirred solutions
      on both sides, the transfer rate is 50% higher in the basal-to-apical than in the
      apical-to-basal direction. Nonlabeled nitrofurantoin (500 microM) in the basal
      chamber equalized the transport in both directions, suggesting that a specific
      transporter is responsible for the basal-to-apical increment in flux. From
      inhibition studies, the apparent affinity of this transporter for nitrofurantoin
      is 50 microM. Changes in pH between 6.4 and 7.8 had no effect on the active
      transport component of the flux but did affect the passive flux component.
      Passive flux of the nonionized molecule was 2.6 times faster than that of the
      ionized molecule, but the ionized molecule did appear to cross the membrane
      passively. Our findings show that nitrofurantoin is actively transported across a
      mammary epithelial cell monolayer by a transporter whose affinity for
      nitrofurantoin does not depend on the anionic charge on nitrofurantoin. The pH
      dependence of a parallel passive pathway suggests that both nonionized and
      ionized forms of nitrofurantoin cross the membranes of the mammary epithelial
      cell by passive diffusion.

PMID- 9023277
TI  - Active transport of nitrofurantoin across the mammary epithelium in vivo.
AB  - Nitrofurantoin is a commonly used urinary tract antibiotic that has been found at
      high concentrations in human milk. In vivo studies in rats were carried out to
      determine the mechanism by which this drug crosses the mammary epithelium.
      Lactating rats were gavage-fed with nitrofurantoin, and their milk and plasma
      levels of the antibiotic were measured at intervals up to 8 hr. The average milk
      to-plasma (M/P) ratio, calculated from the areas under the milk and plasma
      curves, respectively, was 23 compared with a ratio predicted to be about 0.3 on
      the basis of lipid partitioning and protein binding determinations. M/P ratios
      for two nitrofurantoin congeners were also calculated. The neutral compound
      furazolidone had a M/P ratio of about 1, as predicted, whereas the basic compound
      furaltadone had a M/P ratio of 3.49 compared with a predicted ratio of 1.4. These
      data suggest that nitrofurantoin and, to a lesser extent, furaltadone are
      actively transported across the mammary epithelium into milk.

PMID- 9023279
TI  - Sino-aortic denervation causes right atrial beta adrenoceptor down-regulation.
AB  - Rat isolated right atria obtained 1 wk after sinoaortic denervation were less
      sensitive to the chronotropic actions of beta-agonists than were tissues obtained
      from animals that underwent sham surgery or no surgery at all. The potencies, but
      not the maximal responses for two high efficacy agonists, norepinephrine and
      isoproterenol, were reduced about 3- to 4-fold. Sino-aortic denervation (SAD)
      caused about a 3-fold decrease in potency and about a 60% decrease in maximal
      response for a low efficacy agonist, prenalterol. The changes in the actions of
      these agonists occurred in the absence of any changes in the subtype of beta
      receptor mediating the chronotropic response. The results of analyses of the data
      for prenalterol showed that SAD caused a decrease in the operational efficacy of
      this agonist without any changes in its KD value for beta-1 adrenoceptors. SAD
      had no effect on the responses of the tissue to blockade of uptake 1 and uptake
      2, suggesting no compensatory changes in the removal processes caused the
      decreased potency. The results of radioligand binding assays showed that SAD
      caused a decrease in the maximal binding of 125I-cyanopindolol without altering
      its KD. Also, the results of competition binding assays confirmed the lack of
      effect of SAD on the KD for prenalterol. The SAD-induced changes in the actions
      of agonists acting at right atrial beta-1 receptors were caused by a down
      regulation of beta-1 adrenoceptors, which probably occurred in response to SAD
      induced increases in sympathetic tone.

PMID- 9023281
TI  - Nonpeptide endothelin receptor antagonists. VIII: attentuation of acute hypoxia
      induced pulmonary hypertension in the dog.
AB  - It has been proposed that endothelin-1 (ET-1), a potent endogenous vasoactive
      peptide, may play an important role in the regulation of pulmonary blood flow.
      The purpose of the present study was to characterize the effects of ET-1 and a
      nonpeptide mixed ET(A) and ET(B) receptor antagonist, SB 209670, in isolated
      segments of the canine pulmonary artery and to examine the effects of SB 209670
      in a canine model of acute hypoxia-induced pulmonary hypertension. In isolated
      segments of the pulmonary artery, SB 209670 (3-300 nM) produced a concentration
      dependent antagonism of contraction elicited by ET-1 (pA2 = 8.9; slope = 0.9) and
      had no effect on phenylephrine responses. In addition, SB 209670 antagonized the
      small, endothelium-dependent relaxation induced by sarafotoxin 6c in
      phenylephrine (10 microM)-precontracted vessels (pKB = 8.6). In anesthetized
      dogs, the driving pressure across the pulmonary circulation increased
      approximately 100% during the hypoxic period (area under the curve [AUC] = 267.1
      +/- 25.3 mm Hg x min). SB 209670 treatment (3 and 30 microg/kg/min i.v.) reduced
      pulmonary vascular resistance and produced a profound dose-related inhibition of
      hypoxia-induced pulmonary hypertension (AUC = 158.3 +/- 22.7 mm Hg x min and 50.1
      +/- 4.9 mm Hg x min, respectively). None of the other hemodynamic or arterial
      blood gas parameters differed significantly in the vehicle and treatment groups.
      In addition, SB 209670 produced a significant reversal of hypoxia-induced
      pulmonary hypertension (AUC = 267.1 +/- 25.3 mm Hg x min vs. 167.8 +/- 23.4 mm Hg
      x min) when administered at the plateau of the hypoxic response. It was found
      that SB 209670 administration significantly elevated plasma levels of ET-1-LI (>
      or = 25-fold). These results suggest that ET-1 is an important mediator of
      hypoxia-induced pulmonary hypertension in the dog and that SB 209670, a potent
      and selective mixed ET(A) and ET(B)receptor antagonist in the pulmonary
      circulation, may represent an important therapeutic approach to the treatment of
      pulmonary hypertension.

PMID- 9023280
TI  - Voltage-dependent calcium channels as targets for convulsant and anticonvulsant
      alkyl-substituted thiobutyrolactones.
AB  - Alkyl-substituted thiobutyrolactones increase or decrease gamma-aminobutyric
      acidA responses at or near the picrotoxin site, but they are structurally similar
      to ethosuximide, which prompted us to determine the actions of thiobutyrolactones
      on voltage-dependent Ca++ currents. We measured Ca++ currents in cultured
      neonatal rat dorsal root ganglion neurons in the absence and presence of the
      anticonvulsant alpha-ethyl,alpha-methyl-gamma-thiobutyrolactone (alpha-EMTBL) and
      the convulsant beta-ethyl,beta-methyl-gamma-thiobutyrolactone (beta-EMTBL). Low
      voltage-activated (T-type) currents were reduced in a concentration-dependent
      manner, with a maximal reduction of 26% and 30% by alpha-EMTBL and beta-EMTBL,
      respectively. alpha-EMTBL reduced high-voltage-activated currents in a
      concentration- and voltage-dependent manner: maximal responses were 7% when
      evoked from -80 mV, with more rapid current inactivation; 29% when evoked from 
      40 mV, with little effect on current inactivation. beta-EMTBL increased high
      voltage-activated currents < or = 20% at 10 to 300 microM, but reduced currents
      at higher concentrations; the latter action was similar to that of alpha-EMTBL in
      its magnitude and voltage dependence. Block of N-type channels with omega
      conotoxin GVIA (10 microM) reduced the effect of alpha-EMTBL and eliminated its
      voltage dependence. The L-type current component was also reduced by alpha-EMTBL,
      with little effect on P- or Q-type current components. The related compound,
      alpha-ethyl,alpha-methyl-gamma-butyrolactone, had no effect on Ca++ currents. We
      conclude that thiobutyrolactones affect voltage-dependent Ca++ currents in a
      concentration- and voltage-dependent manner, with greater potency on low-voltage.
      activated channels. Both the ring structure and the position of its alkyl
      substitutions determine the identity of the targeted Ca++ channel subtypes and
      the manner of regulation.

PMID- 9023282
TI  - Evidence against a cytochrome P450-derived reactive oxygen species as the
      mediator of the nitric oxide-independent vasodilator effect of bradykinin in the
      perfused heart of the rat.
AB  - The coronary vasodilator effect of bradykinin (BK) in the rat is independent of
      NO but dependent on activation of phospholipases with involvement of cytochrome
      P450 mono-oxygenase (P450) and stimulation of Ca++-activated K+ channels,
      implicating an unidentified hyperpolarizing factor generated via P450 metabolism
      of arachidonic acid (AA). Because P450 activity also generates free radicals,
      such as superoxide, which can lead to the formation of hydrogen peroxide and
      hydroxyl radicals, which are vasoactive, we addressed the contribution of
      superoxide to the vasodilator effect of BK in the rat heart. Using rat renal
      microsomes as a source of P450, we verified that P450-dependent metabolism of AA
      generated superoxide, as detected by chemiluminescence with lucigenin. The signal
      was almost abolished by inhibition of P450 with clotrimazole and the superoxide
      scavenger 4,5-dihydroxy-1,3-benzene sulfonic acid. However, base-line superoxide
      formation, detected by chemiluminescence, in cardiac slices and perfused hearts
      was unchanged in response to BK or AA. Furthermore, in perfused hearts treated
      with nitroarginine and indomethacin to eliminate NO and prostaglandins and
      elevate perfusion pressure, dose-dependent vasodilator responses to BK were
      unaffected by superoxide dismutase plus catalase, a combination that abolished
      dilator responses to hydrogen peroxide. Similarly, the superoxide scavengers 4,5
      dihydroxy-1,3-benzene sulfonic acid and 4-hydroxy-2,2,6,6-tetramethylpiperidine
      noxyl were without effect on vasodilator responses to BK. Thus, the coronary
      vasodilator action of BK is independent of superoxide or its derivatives, which
      can be excluded as hyperpolarizing factors mediating NO-independent vasodilation
      in the rat.

PMID- 9023283
TI  - Pharmacological activity and safety profile of P10358, a novel, orally active
      acetylcholinesterase inhibitor for Alzheimer's disease.
AB  - 1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-1(H)-indol-5-yl methyl carbamate
      (P10358) is a potent, reversible acetylcholinesterase inhibitor that produces
      central cholinergic stimulation after oral and parental administration in rats
      and mice. P10358 is a 2.5 times more potent acetylcholinesterase inhibitor than
      THA in vitro (IC50 = 0.10 +/- 0.02 microM vs. IC50 = 0.25 +/- 0.03 microM). It
      also inhibits butyrylcholinesterase activity as potently as THA (IC50 = 0.08 +/-
      0.05 microM vs. IC50 = 0.07 +/- 0.01 microM). Ex vivo, P10358 (0.2 - 20 mg/kg,
      p.o.) produced dose-dependent inhibition of brain acetylcholinesterase activity.
      At 10 and 20 mg/ kg, it produced profound and long-lasting hypothermia in mice.
      P10358 enhanced performance in rats in a step-down passive avoidance task (0.62
      and 1.25 mg/kg) and in a social recognition paradigm (0.32, 0.64 and 1.25 mg/kg)
      in mice. It reversed scopolamine-induced deficits in the Morris Water maze in
      rats (1.25 and 2.5 mg/kg) and a higher dose elevated striatal homovanillic acid
      levels. These behavioral and biochemical effects are consistent with central
      cholinergic stimulation. Hemodynamic studies in the rat demonstrated a 16-fold
      separation between behaviorally active doses (1.25 mg/kg) and those that elevated
      arterial pressure (20 mg/kg). Lethality in rats occurred at an oral dose of 80
      mg/kg, but not at lower doses. Chemically, P10358 is an N-aminoindole and may not
      have the hepatotoxic liability associated with aminoacridine structure of
      tacrine. P10358 had weak affinity (>10 microM) at a variety of aminergic and
      peptidergic receptors and uptake carriers. These properties suggest that P10358
      may be a safe and promising symptomatic treatment for Alzheimer's disease.

PMID- 9023284
TI  - Comparison between alpha-1 adrenoceptor-mediated and beta adrenoceptor-mediated
      inotropic components elicited by norepinephrine in failing human ventricular
      muscle.
AB  - The purpose of our study was to investigate the inotropic response to the
      endogenous agonist norepinephrine mediated through alpha-1 adrenoceptors and to
      compare this response to that mediated through beta-adrenoceptors in failing
      human ventricular myocardium. We studied ex vivo the inotropic effect of
      norepinephrine in isometrically contracting trabecular myocardium from both
      ventricles of explanted hearts. By studying influence of appropriate adrenoceptor
      blockers, qualitative characteristics of the inotropic response and sensitivity
      of the inotropic response to cholinergic stimulation, it was revealed that
      norepinephrine evoked both alpha-1 and beta adrenoceptor-mediated inotropic
      effects in failing human ventricle myocardium. Quantitatively the inotropic
      responses to norepinephrine varied markedly between preparations, but the mean
      responses elicited through the respective adrenoceptor systems were of comparable
      magnitude. Concomitant stimulation of alpha-1 and beta adrenoceptors by
      norepinephrine alone revealed a contribution of an alpha-1 adrenoceptor-mediated
      component to the final and unopposed inotropic response. Differential sensitivity
      of the two adrenoceptor systems to norepinephrine depending on etiology of heart
      failure and possibly also thyroid status was observed. It is concluded that
      norepinephrine evokes an alpha-1 adrenoceptor-mediated inotropic effect
      comparable to that evoked through the beta adrenoceptors in failing human
      ventricular myocardium, and that this alpha-1 adrenoceptor-mediated inotropic
      effect may be of functional importance.

PMID- 9023285
TI  - Inhibition by omeprazole of proguanil metabolism: mechanism of the interaction in
      vitro and prediction of in vivo results from the in vitro experiments.
AB  - Both the antimalarial prodrug proguanil and the gastric proton pump inhibitor
      omeprazole are substrates for cytochrome P450 (CYP)2C19 and CYP3A. However, the
      relative contribution of each enzyme to proguanil bioactivation to cycloguanil
      and to the metabolism of omeprazole, as well as their potential to interact,
      remains to be examined. The bioactivation of proguanil to its active metabolite
      cycloguanil was studied in vitro in human liver microsomes and in vivo in 12
      healthy subjects, in the absence and in the presence of omeprazole. The formation
      of cycloguanil from proguanil exhibited biphasic kinetic behavior in four of six
      human livers, indicating that at least two enzymes are responsible for this
      metabolic step. Cycloguanil formation activity did not correlate with
      immunoreactive CYP3A4 content or with CYP3A4 activity, as measured by
      testosterone 6beta-hydroxylation, suggesting that CYP3A4 plays a limited role in
      cycloguanil formation. Furthermore, troleandomycin (10 microM) inhibited only 10
      to 17% of cycloguanil formation at proguanil concentrations of 100 and 500
      microM. At a proguanil concentration of 20 microM, omeprazole at 10 microM
      inhibited cycloguanil formation in vitro by 47 +/- 59%. These in vitro results
      were consistent with the results of our in vivo study in healthy subjects, which
      showed a 32 +/- 11% decrease in proguanil apparent oral clearance and a 65 +/- 8%
      decrease in proguanil partial metabolic clearance to cycloguanil in the presence
      of omeprazole (both P < .001). We conclude that in vitro studies of proguanil
      metabolism and interactions are predictive of in vivo situations, that CYP2C19 is
      the main enzyme responsible for proguanil bioactivation to cycloguanil and that
      omeprazole inhibits this biotransformation in vitro and in vivo by inhibiting
      this enzyme.

PMID- 9023286
TI  - Differential development and characterization of rapid acute neuronal tolerance
      to the depressant effects of ethanol on cerebellar Purkinje neurons of low
      alcohol-sensitive and high-alcohol-sensitive rats.
AB  - Rapid acute neuronal tolerance (RANT) to the depressant effects of ethanol (EtOH)
      is a desensitization of EtOH-induced depression of neuronal firing that develops
      over the first 5 to 7 min of EtOH exposure. This phenomenon has been hypothesized
      to play a role in acute behavioral insensitivity to EtOH and is expressed by
      cerebellar Purkinje neurons in animals selectively bred for insensitivity to EtOH
      induced ataxia, such as low-alcohol-sensitive (LAS) rats and short-sleep mice.
      Purkinje neurons of animals bred for high sensitivity to EtOH-induced behavioral
      ataxia, such as high-alcohol-sensitive (HAS) rats and long-sleep mice, only
      infrequently express such acute tolerance to EtOH-induced depression of neuronal
      activity. However, because higher EtOH doses are required to depress Purkinje
      neuron activity in LAS rats than in HAS rats, it was not known whether the higher
      EtOH doses that depress LAS neurons would also induce RANT to EtOH in HAS rats,
      which were generally not exposed to such high EtOH doses in previous studies.
      Furthermore, the conditions for development and maintenance of RANT to EtOH had
      not been characterized. We found that RANT to EtOH-induced depression of
      cerebellar neurons principally developed within 5 min of EtOH application and
      recovered within 20 min of the last EtOH exposure and that neurons in HAS rats
      did not develop acute tolerance to the higher EtOH doses that were effective in
      LAS rats. We conclude that this rapid tolerance contributes to the acute EtOH
      sensitivity difference between LAS and HAS rats.

PMID- 9023287
TI  - Size-dependent permeability of hydrophilic probes across rabbit colonic
      epithelium.
AB  - Colon-specific delivery of metabolically labile molecules, such as proteins and
      peptides, is of particular interest in pharmaceutical research. Among the factors
      that may influence the permeability of drug molecules across colonic mucosa are
      their molecular weight and geometry. The purpose of this study was to evaluate
      the influence of molecular geometry on in vitro permeability across rabbit distal
      colonic epithelia. Permeability of radiolabeled hydrophilic probes with different
      molecular weights and geometries across isolated rabbit distal colonic tissue was
      evaluated by means of the Ussing chamber technique. The hydrodynamic radii of the
      probes (an indicator of molecular geometry) were estimated by theoretical models
      as well as dynamic light scattering. We conducted the permeability studies in the
      presence and absence of the epithelial cells to evaluate the contribution of the
      underlying connective tissue to the overall in vitro permeability across the
      colonic mucosa. The rank order of the permeability of the markers was mannitol >
      lactulose > polyethylene glycol (PEG) 400 > PEG 900 > PEG 4000, which is
      consistent with their molecular weights and estimated hydrodynamic radii. The
      permeability of inulin, a polyfructose molecule with a molecular weight of about
      5000, however, was approximately the same as that of PEG 900 (molecular weight
      about 900). When the epithelial cells were removed, for the homologous series of
      PEGs, the permeabilities were proportional to their free diffusion coefficients
      in water. It appears that for the PEG and lactulose probes, theoretical
      estimation of the hydrodynamic radii, which assumes the molecules to be spherical
      in shape, provides a good basis for the dependence of permeability on geometry.
      The relatively high permeability of inulin seems to be due to its compact
      structure. The PEG permeability values in the absence of epithelial cells, in
      combination with their diffusion coefficients, indicate that the underlying
      connective tissue does not contribute to the overall permeability of these
      molecules across colonic mucosa in vitro.

PMID- 9023288
TI  - Central injection of a new corticotropin-releasing factor (CRF) antagonist,
      astressin, blocks CRF- and stress-related alterations of gastric and colonic
      motor function.
AB  - The influence of central injection of a new corticotropin releasing factor (CRF)
      antagonist, astressin, [cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]r/ hCRF12-41)],
      on exogenous and endogenous CRF-induced gastric ileus and stimulation of bowel
      discharges was investigated in conscious rats. Intracisternal (ic) CRF (0.6
      microg) reduced gastric emptying of a noncaloric solution to 17.1 +/- 4.9%
      compared with 50.1 +/- 4.6% in control group injected i.c. with vehicle.
      Astressin (1,3 and 10 microg, i.c.) dose dependently prevented ic CRF-induced
      delayed gastric emptying by 33, 100 and 100%, respectively, and had no effect on
      basal gastric emptying. Abdominal surgery with cecal manipulation (1 min) reduced
      gastric emptying to 19.8 +/- 5.5% 3 hr postsurgery compared with 59.9 +/- 5.2%
      after anesthesia alone plus i.c. vehicle. Astressin (1,3 and 10 microg, i.c.)
      prevented postoperative gastric ileus by 56, 93 and 92%, respectively.
      Intracerebroventricular CRF (0.6 microg) and water-avoidance stress stimulated
      pellet output (number/60 min) to 5 +/- 1 and 11 +/- 2, respectively, compared
      with no fecal pellet output after i.c.v. vehicle and no exposure to stress.
      Astressin (3 and 10 microg, i.c.v.) blocked exogenous CRF action by 47 and 63%,
      respectively, and colonic response to stress by 0 and 54%, respectively. These
      data indicate that astressin injected into the CSF at low doses (1-10 microg) has
      an antagonistic action against CRF and stress-related alterations of
      gastrointestinal motor function, without an intrinsic effect in these in vivo
      systems. Astressin may be a useful tool to explore functional CRF-dependent
      physiological pathways in specific brain nuclei.

PMID- 9023290
TI  - Effect of lobaric acid on cysteinyl-leukotriene formation and contractile
      activity of guinea pig taenia coli.
AB  - Lobaric acid, a constituent of the lichen Stereocaulon alpinum, was investigated
      for effects on the smooth muscle taenia coli from guinea pigs. Inhibitory effects
      of lobaric acid on spontaneous contractile activity and on contractile activity
      stimulated by ionophore A23187 were studied. In addition, the activity of lobaric
      acid on ionophore-induced generation of cysteinyl-leukotrienes in taenia coli was
      determined by enzyme immunoassay. Lobaric acid significantly reduced spontaneous
      contractile activity of the muscle and inhibited contractions caused by ionophore
      A23187 with an effective dose of 5.8 microM. Increased contractility caused by
      leukotriene D4 was not influenced by lobaric acid. Lobaric acid inhibited the
      formation of cysteinyl-leukotrienes as determined by enzyme immunoassay with an
      effective dose of 5.5 microM.

PMID- 9023289
TI  - Differential involvement of serotonin 2A/C and thromboxane A2/prostanoid
      receptors in high- vs. low-shear rate arterial thrombosis in rabbits.
AB  - Experiments performed in 226 pentobarbitone-anesthetized rabbits were designed to
      investigate the involvement of thromboxane/prostanoid and 5-hydroxytryptamine (5
      HT)2A/C receptors during arterial thrombus formation in distinct low- and high
      shear rate thrombosis models. Antithrombotic activities of the
      thromboxane/prostanoid receptor antagonist SQ 29,548 and two chemically distinct
      5-HT2A/C receptor antagonists, ritanserin and ketanserin, were assessed first in
      low-shear rate (approximately 600 sec(-1)) arterial thrombosis, produced by
      insertion of a silk thread as thrombogenic substrate into the central section of
      an extracorporeal arteriovenous shunt established between the left carotid artery
      and the right jugular vein (n = 77), and second in high-shear rate (approximately
      40,000 sec(-1)) arterial thrombosis, produced by critical stenosis and local
      endothelial injury of a carotid artery, characterized by cyclic flow reductions
      (CFRs) due to recurrent platelet aggregation and subsequent dislodgement of the
      thrombus (n = 149). Under low shear rate, SQ 29,548 (10-2500 microg/kg plus 10
      2500 microg/kg/hr i.v.), but not ritanserin or ketanserin (both at 2500 microg/kg
      i.v.), dose-dependently inhibited thrombus formation. In contrast, under high
      shear rate, SQ 29,548 (10-160 microg/kg plus 10-160 microg/kg/hr i.v.) and both
      ritanserin and ketanserin (both at 10-2500 microg/kg i.v.) dose-dependently
      reduced CFR frequency, with ID50 values of 35 microg/kg (95% confidence limits,
      24-58 microg/kg), 77 microg/kg (95% confidence limits, 40-132 microg/kg) and 89
      microg/kg (95% confidence limits, 36-285 microg/kg) i.v., respectively.
      Furthermore, local infusion of the stable thromboxane A2 analog U-46619 (0.63
      microg/kg/min) or 5-HT (20.8 microg/kg/min) proximal to the site of injury and
      stenosis in rabbits pretreated with either SQ 29,548 (40 microg/kg plus 40
      microg/kg/hr i.v.) or ritanserin (160 microg/kg i.v.), respectively, restored CFR
      frequency to vehicle group levels in animals whose CFR frequency was previously
      reduced. The inhibitory activity of ketanserin and ritanserin on CFRs could not
      be attributed to 5-HT1B/D or alpha-1 adrenoceptor antagonist properties or to any
      hypotensive activity. These results provide firm evidence that
      thromboxane/prostanoid receptors are involved in arterial thrombosis in rabbits
      independently of the shear rate, whereas 5-HT2A/C receptors play a major role
      only in high-shear rate thrombus formation.

PMID- 9023291
TI  - LY303870, a centrally active neurokinin-1 antagonist with a long duration of
      action.
AB  - The selective neurokinin (NK)-1 antagonist LY303870 has high affinity and
      specificity for human and guinea pig brain NK-1 receptors labeled with 125I
      substance P. It has approximately 15- to 30-fold lower affinity for rat and mouse
      brain NK-1 receptors, consistent with previously reported species differences in
      the affinities of nonpeptide antagonists for NK-1 receptors. In vivo, LY303870
      blocked the characteristic, caudally directed, biting and scratching response
      elicited by intrathecal administration of the selective NK-1 agonist Ac
      [Arg6,Sar9,Met(O2)11]substance P6-11 in conscious mice. The potentiation of the
      tail-flick response elicited by intrathecal administration of the NK-1 agonist
      [Sar9,Met(O2)11]substance P in rats was also selectively blocked by LY303870.
      When tested in a model of persistent nociceptive activation induced by tissue
      injury (the formalin test), LY303870 blocked licking behavior in the late phase
      of the formalin test, in a dose-dependent manner. After oral administration of 10
      mg/kg, the blockade of the late-phase licking behavior was evident for at least
      24 hr. Ex vivo binding studies in guinea pigs showed that orally administered
      LY303870 potently inhibited binding to central and peripheral NK-1 receptors
      labeled with 125I-substance P. This inhibition was long-lasting, consistent with
      other in vivo activities. LY306155, the opposite enantiomer of LY303870, was less
      active in all of the functional assays. In rodents, LY303870 did not exhibit any
      neurological, motor, cardiovascular, gastrointestinal or autonomic side effects
      at doses of < or = 50 mg/kg p.o. Thus, LY303870 is a potent, centrally active, NK
      1 antagonist in vivo, with long-lasting oral activity.

PMID- 9023292
TI  - Neutrophils accentuate renal cold ischemia-reperfusion injury. Dose-dependent
      protective effect of a platelet-activating factor receptor antagonist.
AB  - This study was undertaken to evaluate whether the renal damage induced by cold
      ischemia-reperfusion was worsened by neutrophils (PMN), and if blockade of
      platelet-activating factor (PAF) could effectively decrease this injury. After
      flushing with EuroCollins, 85 kidneys from Sprague-Dawley rats underwent either
      no cold ischemia or a 4-h cold ischemia, and then were reperfused for 75 min at
      37 degrees C and 100 mm Hg in an isolated perfusion circuit. Reperfusion was
      performed with a Krebs-Henseleit solution containing 4.5% albumin, with and
      without human PMN (7.5 x 10(5) cells/ml) and with and without addition of a PAF
      receptor antagonist (BN 52021). Hemodynamic and functional parameters were
      continuously assessed during reperfusion. At end of the study, PAF production was
      evaluated. Presence of PMN during reperfusion of nonischemic kidneys produced no
      alteration of functional parameters or PAF production. After 4-h cold ischemia,
      the presence of PMN during reperfusion produced a significant worsening of plasma
      flow rate, glomerular filtration rate and sodium reabsorption in comparison with
      kidneys reperfused without PMN. Also, higher production of PAF was observed in
      the kidneys reperfused with PMN than in the kidneys reperfused without PMN. After
      4-h cold ischemia, addition of BN 52021 during reperfusion in the presence of PMN
      significantly increased the plasma flow rate, glomerular filtration rate and
      sodium reabsorption in comparison with kidneys reperfused without this PAF
      antagonist. This effect was dose dependent. After 4-h cold ischemia, addition of
      BN 52021 during reperfusion in the absence of PMN produced no significant effect
      on functional parameters in comparison with kidneys reperfused without this PAF
      antagonist. These results indicate that PMN contribute to renal cold ischemia
      reperfusion injury evaluated in the isolated perfused kidney. Treatment with a
      PAF receptor antagonist attenuated this injury in a dose-dependent manner, which
      suggests that it is mediated by PAF.

PMID- 9023293
TI  - Nitrous oxide enhances Na+/Ca++ exchange in the neuroblastoma cell line SK-N-SH.
AB  - Changes in the concentration of cytosolic free calcium ([Ca++]i) play fundamental
      roles in the initiation and regulation of many neuronal processes. Altered
      regulation of [Ca++]i has been implicated in the action of some anesthetics. We
      investigated the effects of nitrous oxide (N2O) on Ca++ mobilization and membrane
      potential in the human neuroblastoma cell line SK-N-SH. [Ca++]i was monitored by
      fluorescence spectrophotometry of cells loaded with fura-2 or fluo-3. N2O
      reversibly suppressed carbachol-stimulated increases in [Ca++]i. N2O also
      inhibited increases in [Ca++]i induced by calcium ionophore or depolarization
      suggesting a mechanism involving enhanced efflux or sequestration of cytosolic
      Ca++. The inhibitory effect of N2O was attenuated when the transmembrane Na+
      gradient was altered either by suspending cells in nominally Na(+)-free buffer or
      by pretreating cells with ouabain. The inhibitory effect of N2O was also
      attenuated by the Na+/Ca++ exchange inhibitor 3,4-dichlorobenzamil. The effects
      of N2O on membrane potential were measured fluorimetrically using bis(1,3
      dibutylthiobarbituric acid)-trimethine oxonol. In the presence of N2O, resting
      membrane potential was hyperpolarized, a condition that would favor Ca++ efflux
      mediated by the electrogenic Na+/Ca++ exchanger. Taken together, these findings
      indicate that N2O suppresses carbachol-stimulated increases in [Ca++]i by
      enhancing Na+/Ca++ exchange activity. Enhancement of neuronal Na+/Ca++ exchange
      may contribute to the anesthetic action of N2O.

PMID- 9023294
TI  - Biochemical and pharmacological activities of SR 142948A, a new potent
      neurotensin receptor antagonist.
AB  - SR 142948A, 2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methylc
      arbamoyl)-2-isopropylphenyl)-1H-pyrazole3-carbonyl]amino] adamantane-2-carboxylic
      acid, hydrochloride, a new and extremely potent neurotensin (NT) receptor
      antagonist, has been characterized in comparison with SR 48692. This selective
      compound possesses nanomolar affinities for NT receptors, recognizes the two
      binding sites described for the NT receptor and fully displaces [3H]SR 48692
      specific binding. SR 142948A antagonizes the classical in vitro NT effects, i.e.,
      inositol monophosphate formation in HT 29 cells (IC50 = 3.9 nM) or intracellular
      calcium mobilization in Chinese hamster ovary cells transfected with the human
      receptor. It dose-dependently (0.04-640 x 10(-3) mg/kg p.o.) inhibits the turning
      behavior induced by unilateral intrastriatal injection of NT in mice, with the
      biphasic profile previously seen for SR 48692. At 0.1 mg/kg (i.p.), it completely
      antagonizes NT-evoked acetylcholine release in the rat striatum. In contrast to
      SR 48692, SR 142948A (p.o.) blocks both hypothermia and analgesia induced by
      i.c.v. injection of NT (mice and/or rats) but is unable to modify the dopamine
      release evoked by NT injection into the ventral tegmental area. In summary, SR
      142948A retains the properties of the lead compound SR 48692 (no intrinsic
      agonist activity, oral bioavailability, long duration of action and good brain
      access), reveals a wider spectrum of activity than SR 48692 (probably due to the
      inhibition of NT receptor subtypes) and represents an additional tool for further
      exploration of the therapeutic potential of this class of compounds.

PMID- 9023295
TI  - In vivo and in vitro evidence for nonrestricted transport of 2',7'-bis(2
      carboxyethyl)-5(6)-carboxyfluorescein tetraacetoxymethyl ester at the blood-brain
      barrier.
AB  - 2' ,7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein tetraacetoxymethyl ester
      (BCECF-AM), a fluorescence reagent for the measurement of intracellular pH with a
      molecular weight of 809 Da, was used to test the hypothesis that the blood-brain
      barrier (BBB) does not restrict the influx of substrate with a molecular weight
      greater than 600 Da. Using cultured bovine brain capillary endothelial cells
      (BCEC), the influx rate of BCECF-AM was found to be 151 +/- 2 microl/min/mg
      protein and was extrapolated to give 446 +/- 7 microl/min/g brain as a BBB
      permeability surface area product (PS). No significant saturation was observed
      for the initial in vitro uptake of BCECF-AM into BCEC at concentrations 0.1, 1.0
      and 5.0 microM. The apparent activation energy of the initial uptake of BCECF-AM
      was found to be 5.09 kcal/mol. These results suggest that BCECF-AM is transported
      into the BBB by passive diffusion. The in vivo BBB PS value was also found to be
      295 +/- 48 microl/min/g brain and 132 +/- 24 microl/min/g brain by the in situ
      brain perfusion and the carotid artery injection methods, respectively. No
      significant efflux of BCECF-AM from the brain was observed over a 120 sec washout
      period, suggesting that BCECF-AM is immediately hydrolyzed to BCECF, a
      hydrophilic analogue, in the brain after crossing the BBB. The octanol/water
      partition coefficient of BCECF-AM was found to be 5.66 +/- 0.27. The BBB PS value
      of BCECF-AM was predicted to be 105 microl/min/g brain, based on the relationship
      between the BBB PS value and the value of partition coefficient divided by the
      square root of the molecular weight. These results demonstrate that BCECF-AM
      transport across the BBB is not restricted despite its large molecular size.

PMID- 9023296
TI  - Genetic differences in behavioral sensitivity to a neuroactive steroid.
AB  - Recent work found that lower endogenous levels of the gamma-aminobutyric acid
      agonist, neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha
      THP) may be correlated with increased ethanol withdrawal severity in the
      selectively bred Withdrawal Seizure-Prone and -Resistant mice. The present
      studies were conducted to determine whether decreased sensitivity to
      3alpha,5alpha-THP was correlated with ethanol withdrawal hyperexcitability in
      another genetic mouse model, namely the C57BL/6 (B6) and DBA/2 (D2) inbred
      strains. These strains also differ in ethanol withdrawal severity (D2 >> B6). B6
      and D2 male mice were injected with 3alpha,5alpha-THP (0-10 mg/kg i.p.) 15 min
      before the timed tail vein infusion of pentylenetetrazol. B6 mice were more
      sensitive than D2 animals to the anticonvulsant effect of 3alpha,5alpha-THP.
      Subsequent studies measured sensitivity to several of the pharmacological effects
      of 3alpha,5alpha-THP. B6 and D2 male mice were injected with 3alpha,5alpha-THP (0
      32 mg/kg) before testing for locomotor activation (total number of entries) and
      anxiolysis (percent open arm entries) on the elevated plus maze, muscle
      relaxation (impairment of forelimb grip strength), ataxia (impairment of Rotarod
      performance) and seizure susceptibility to pentylenetetrazol. B6 mice were more
      sensitive than D2 animals to the anxiolytic, locomotor stimulant and
      anticonvulsant effects of 3alpha,5alpha-THP. In contrast, D2 mice were more
      sensitive than B6 mice to 3alpha,5alpha-THP-induced muscle relaxation and ataxia.
      Plasma 3alpha,5alpha-THP levels did not differ in the B6 and D2 mice injected
      with this steroid, suggesting that the strain differences were not
      pharmacokinetic. Collectively, the results in selectively bred Withdrawal Seizure
      Prone and -Resistant mice and B6 and D2 inbred strains suggest that genetic
      differences in neuroactive steroid sensitivity and biosynthesis may contribute to
      ethanol withdrawal severity.

PMID- 9023297
TI  - Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve
      injury evoked allodynia in the rat.
AB  - Neuropathic pain remains a significant clinical problem. Current understanding
      implicates the spinal cord dorsal horn N-methyl-d-aspartate (NMDA) receptor
      apparatus in its pathogenesis. Previous reports have described NMDA antagonist
      reduction of nerve injury-induced thermal hyperalgesia and formalin injection
      related electrical activity. We examined a panel of spinally administered NMDA
      antagonists in two models: allodynia evoked by tight ligation of the fifth and
      sixth lumbar spinal nerves (a model of chronic nerve injury pain), and the
      formalin paw test (a model wherein pretreatment with drug may preempt the
      development of a pain state). A wide range of efficacies was observed. In the
      nerve injury model, order of efficacy (expressed as percent of maximum possible
      effect +/- S.E.), at the maximum dose not yielding motor impairment, was
      memantine (96 +/- 5%) = AP5 (91 +/- 7%) > dextrorphan (64 +/- 11%) =
      dextromethorphan (65 +/- 22%) > MK801 (34 +/- 8%) > ketamine (18 +/- 6%). For the
      formalin test, the order of efficacy was AP5 (86 +/- 9%) > memantine (74 +/- 5%)
      > or = MK801 (67 +/- 16%) > dextrorphan (47 +/- 16%) > dextromethorphan (31 +/-
      12%) > ketamine (17 +/- 15%). In the nerve injury model, no supraspinal action
      was seen after intracerebroventricular injections of dextromethorphan and
      ketamine. NMDA antagonists by the spinal route appear to be useful therapeutic
      agents for chemically induced facilitated pain as well as nerve injury induced
      tactile allodynia. It is not known what accounts for the wide range of
      efficacies.

PMID- 9023298
TI  - Effects of uricosuric and antiuricosuric agents on urate transport in human brush
      border membrane vesicles.
AB  - Inhibition of [14C]-urate uptake by uricosuric and antiuricosuric agents was
      investigated in human brush-border membrane vesicles, urate being transported
      either by anion exchange mechanisms or by voltage sensitive pathway. The IC50 for
      drugs on [14C]-urate uptake in vesicles loaded with 1 mM cold urate or with 5 mM
      lactate was, respectively: 0.7 and 0.3 microM for benzbromarone; 6 and 4 microM
      for salicylate; 133 and 13 microM for losartan; 520 and 190 microM for
      sulfinpyrazone and 807 and 150 microM, for probenecid. The IC50 ratio for [14C]
      urate uptake in exchange for cold urate or for lactate varied from about 1 for
      salicylate to 10 for losartan, supporting the hypothesis that two distinct anion
      exchangers are involved in urate transport. Application of Hill equation revealed
      that urate/anion exchangers have more than one binding site, possibly two binding
      sites with high cooperativity, for benzbromarone and sulfinpyrazone, but only one
      for probenecid, salicylate and losartan. The uricosuric diuretic, tienilic acid
      was 10 to 50 times more potent than hydrochlorothiazide, chlorothiazide and
      furosemide, for inhibiting [14C]-urate uptake in exchange for cold urate. This
      higher potency is the reason of its uricosuric properties. All uricosuric agents,
      as well as the antiuricosuric agents, pyrazinoate and ethambutol, had a much
      lower potency for inhibiting [14C]-urate uptake through the voltage sensitive
      pathway (apical secretory step) than through the urate/anion exchangers. This
      suggests that antiuricosuria, induced by pyrazinoate and ethambutol, as well as
      by low concentrations of uricosuric agents, does not result from an inhibition of
      the apical voltage sensitive pathway.

PMID- 9023299
TI  - Antiinflammatory and analgesic activity of an inhibitor of neuropeptide
      amidation.
AB  - 4-Phenyl-3-butenoic acid (PBA) has been shown in vitro to be a turnover-dependent
      inactivator of peptidylglycine alpha-monooxygenase (PAM), the rate-limiting
      enzyme involved in the formation of amidated neuropeptides from their glycine
      extended precursors. In the studies reported herein, we have shown that PBA
      produces a dose-dependent (50-500 mg/kg s.c.) inhibition of serum PAM activity in
      normal rats without affecting peptidylamidoglycolate lyase activity. Because
      amidated neuropeptides such as substance P and calcitonin gene-related peptide
      are involved in acute inflammation, we evaluated the effects of PBA on
      carrageenan-induced inflammation in rats. The acute administration of PBA (s.c.
      or i.p.) produced a dose-related inhibition of edema with maximum inhibition
      (67%) observed at 2 hr postphlogistic agent. In addition, the continuous
      administration of PBA to animals over a 7-day period using osmotic pumps not only
      inhibited hind paw swelling induced by carrageenan but also inhibited serum PAM
      activity and reduced tissue levels of substance P in hind paws. These results
      demonstrate for the first time a correlation between the antiinflammatory
      activity produced by an inhibitor of peptide amidation with its ability to
      inhibit serum PAM activity and lower endogenous tissue levels of substance P.
      Moreover, these results confirm our contention that PAM is an excellent
      pharmacological target for controlling the acute inflammatory response. We also
      demonstrate the ability of PBA to inhibit phenyl-p-quinone and acetylcholine
      induced writhing in mice without affecting the spinally mediated tail immersion
      assay in rats. Because this analgesic effect was extremely rapid (within 15 min),
      PBA may be producing this effect by a mechanism other than peptide amidation.

PMID- 9023300
TI  - Inhibition of reinforcing effects of morphine and motivational aspects of
      naloxone-precipitated opioid withdrawal by N-methyl-D-aspartate receptor
      antagonist, memantine.
AB  - The present study focused on the effects of 1-amino-3,5-dimethyladamantane
      (memantine), a clinically used, low-affinity N-methyl-D-aspartate channel
      blocker, on the motivational impact of morphine and morphine withdrawal syndrome.
      Memantine (7.5 mg/kg) inhibited the acquisition as well as the expression of
      morphine-induced conditioned place preference. However, memantine did not affect
      significantly the acquisition or expression of conditioned place preference
      induced by food presentation. In addition, at the dose that blocked morphine
      induced conditioned place preference, memantine by itself produced neither
      conditioned place preference nor conditioned place aversion. Memantine attenuated
      the negative motivational aspects of morphine withdrawal as assessed by
      conditioned place aversion produced by a low dose (0.1 mg/kg) of naloxone in
      morphine-dependent rats. Drug discrimination studies revealed that the inhibitory
      effects of memantine on morphine-induced conditioned place preference could not
      be attributed to the attenuation by memantine of the interoceptive cue produced
      by morphine. In addition, the inhibitory effects of memantine on the expression
      of morphine-induced conditioned place preference seemed not to be related to
      effects on memory retrieval, as revealed in the Morris water maze spatial task.
      These data suggest that memantine at a low, pharmacologically relevant dose of
      7.5 mg/kg blocks the reinforcing effects of morphine and aversive effects of
      morphine withdrawal in rats, which suggests a new potential clinical indication
      for this agent in the treatment of opioid abuse.

PMID- 9023301
TI  - The effect of hydralazine on the development of tolerance to continuous
      nitroglycerin.
AB  - It has been reported that nitroglycerin (GTN) tolerance can be prevented by the
      concurrent administration of hydralazine. Although the mechanism of this effect
      remains unknown, it is possible that hydralazine modifies counter-regulatory
      responses to nitrate administration. To address this question, we examined the
      impact of hydralazine therapy on the development of tolerance during sustained
      therapy with GTN. Twenty normal volunteers and 18 patients with chronic heart
      failure (mean ejection fraction 30 +/- 2%) were treated for 1 week with
      hydralazine or placebo in a randomized double-blind fashion. Hydralazine therapy
      (or placebo) was continued, and subjects then received continuous transdermal GTN
      for 5 to 7 days. On the first and last day of transdermal GTN therapy, standing
      HR, systolic blood pressure and hematocrit responses were assessed. HR and blood
      pressure responses to sublingual GTN (0.6 mg) were also evaluated before and
      during sustained transdermal GTN therapy. Significant loss of the hemodynamic
      effects of transdermal GTN occurred during sustained therapy in both the normal
      volunteer and heart failure groups. Hydralazine had no effect on the development
      of tolerance to the hemodynamic effect of GTN in either group. In both,
      transdermal GTN therapy was associated with a significant fall in hematocrit that
      persisted for the entire treatment period. Hydralazine had no effect on this
      response. These data suggest that hydralazine therapy does not prevent loss of
      systemic arterial effects or prevent plasma volume expansion during sustained
      transdermal GTN therapy.

PMID- 9023302
TI  - Early nociceptive events influence the temporal profile, but not the magnitude,
      of the tonic response to subcutaneous formalin: effects with remifentanil.
AB  - Injection of dilute formalin into the hindpaw produces brief (phase 1) and
      persistent (phase 2) nociceptive responses in the rat. We recently reported that
      ongoing peripheral nerve input is required for the expression of behavioral and
      cardiovascular responses during phase 2. Here we evaluated the contribution of
      central and peripheral sensitization mechanisms, generated during phase 1, to the
      magnitude and temporal profile of phase 2. During phase 1, we administered
      analgesic doses of an ultrashort-acting opioid, remifentanil (i.v. administration
      from 0-5 min after 5.0% formalin injection), or anesthetic concentrations of
      halothane (2.1%). Inhibition of phase 1 did not reduce the magnitude of flinching
      and cardiovascular responses during phase 2, but it did delay their onset and/or
      termination. Longer remifentanil infusions (0-15 or 0-30 min) produced even
      longer delays (up to 30 min) in the onset and termination of flinching during
      phase 2; however, when remifentanil was administered during the early part of
      phase 2 (15-30 or 15-45 min), it did not prolong the time to termination of phase
      2. Continuous infusion (10 mg/kg/hr i.v.) of a peripherally acting opiate
      antagonist, naloxone methiodide, did not reduce the antinociception produced by
      remifentanil during phase 1 but almost completely reversed the delay in the onset
      and termination of phase 2. We conclude that central sensitization mechanisms
      during phase 1 do not influence the magnitude of phase 2. We also hypothesize
      that remifentanil interacts with peripheral opioid receptors to impede the
      formalin-evoked synthesis and/or release of proinflammatory compounds during
      phase 1 and thus delay phase 2.

PMID- 9023303
TI  - Disposition of amodiaquine and related antimalarial agents in human neutrophils:
      implications for drug design.
AB  - The development and clinical use of 4-aminoquinoline antimalarial agents such as
      amodiaquine have been limited by toxicity to neutrophils. We have investigated
      the chemical basis of amodiaquine-induced toxicity and compared the findings with
      those for established antimalarial drugs proposed for human use. Amodiaquine,
      like chloroquine, mefloquine and halofantrine, was lysosomotropic and accumulated
      in human neutrophils. Amodiaquine did not lead to impairment of either cellular
      function or cell viability at therapeutic levels. In contrast to other
      antimalarial agents, amodiaquine (because it contains a 4-aminophenol function)
      depleted glutathione in activated neutrophils, by formation of an electrophilic
      quinoneimine metabolite. Bioactivation was accompanied by the expression of a
      drug-related antigen on the cell surface, which was recognized by drug-specific
      antibodies, suggesting that a type II hypersensitivity reaction is responsible
      for the observed toxicity. Similar bioactivation and accumulation were observed
      for the structurally related amopyroquine. The effects of chemical modifications
      at the 3'- and 5'-positions, which are known to enhance antimalarial activity,
      were also investigated. The introduction of a lipophilic 5'-chlorophenyl group
      and 3'-t-butyl group blocked bioactivation but enhanced cellular accumulation,
      with resultant impairment of function and neutrophil viability, whereas
      introduction of a second cationic dialkylamino group (bis-mannich compounds)
      blocked bioactivation and reduced cellular accumulation, without producing
      noticeable effects on cellular function and viability. These data provide a
      chemical rationale for the idiosyncratic agranulocytosis observed with
      amodiaquine, and they suggest that similar toxicity might be anticipated for
      amopyroquine but is less likely with bis-mannich antimalarial agents such as
      pyronaridine.

PMID- 9023304
TI  - Effects of LY215490, a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptor antagonist, on the micturition reflex in the rat.
AB  - The effects of glutamate receptor antagonists on urinary bladder and external
      urethral sphincter- (EUS) electromyogram (EMG) activity were evaluated in
      unanesthetized decerebrate rats. In normal rats, LY215490, an alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, in small
      i.v. doses (1-3 mg/kg) decreased bladder contraction amplitude (BC-Amp) by 29%
      and EUS-EMG by 41%; whereas a large dose (10 mg/kg) completely abolished bladder
      and EUS-EMG activity. LY215490 injected intrathecally in small doses (0.01-0.1
      microg) decreased BC-Amp by 20% and EUS-EMG by 62%; whereas large doses (1-10
      microg) completely abolished bladder and EUS-EMG activity. LY215490 (0.1 microg
      i.t.) increased bladder capacity by 28% and decreased voiding efficiency by 44%.
      Combined i.t. administration of small doses of LY215490 (0.1 microg) and MK-801
      (1 microg), an N-methyl-D-aspartate (NMDA) receptor antagonist, which
      individually had little effect on BC-Amp, markedly suppressed bladder activity.
      In chronic spinal rats, LY215490 (10 mg/kg i.v.) abolished EUS-EMG activity and
      decreased BC-Amp by 41%. Intrathecal injections of LY215490 were also less
      effective in chronic spinal rats; a 10-microg dose producing only a partial block
      (53%) of BC-Amp, but complete block of EUS-EMG. In chronic spinal rats, MK-801 (1
      mg/kg i.v.) abolished EUS-EMG activity and decreased BC-Amp by 36%. Pretreatment
      with MK-801 (1 mg/kg i.v.) did not enhance the effect of LY215490 on bladder
      activity in chronic spinal rats. These data suggest that AMPA glutamate receptors
      have a major role in the excitatory pathways controlling bladder and EUS activity
      in spinal cord intact rats. However, in chronic spinal rats, AMPA and NMDA
      receptors are essential for EUS reflexes, but are responsible for only a part of
      reflex bladder activity.

PMID- 9023305
TI  - Effects of sarafotoxin S6c on antidiuresis and norepinephrine overflow induced by
      stimulation of renal nerves in anesthetized dogs.
AB  - We previously reported that endothelin (ET) may function as an inhibitory
      modulator of renal noradrenergic neurotransmission (Suzuki et al., J. Cardiovasc.
      Pharmacol. 19: 905-910, 1992). In our study, we examined the effect of
      sarafotoxin S6c (S6c), a selective ET(B) receptor agonist, on changes in renal
      function and norepinephrine overflow induced by renal nerve stimulation (RNS) in
      anesthetized dogs. RNS at a low frequency (0.5-2.0 Hz) caused significant
      decreases in urine flow, urinary excretion of sodium and fractional excretion of
      sodium and increased norepinephrine secretion rate, without affecting systemic
      and renal hemodynamics. RNS at a high frequency (2.5-5.0 Hz), which diminishes
      renal hemodynamics, produced more potent decreases in urine formation and
      increase in norepinephrine secretion rate than seen with low frequency RNS. When
      S6c (1 ng/kg/min) was infused intrarenally, there was a slight and transient
      increase in renal blood flow, and then this response was followed by a gradual
      reduction. S6c administration produced increase in the basal level of urine flow
      with no apparent effects on urinary excretion of sodium and fractional excretion
      of sodium. During S6c infusion, low frequency RNS-induced antidiuretic action and
      increase in norepinephrine secretion rate were markedly attenuated.
      Qualitatively, similar results were observed in the case of high frequency RNS.
      In addition, high frequency RNS-induced decreases in glomerular filtration rate
      and filtration fraction were significantly suppressed by S6c infusion. Taken
      together with our previous findings, it seems likely that ET plays an important
      role as an inhibitory modulator of renal noradrenergic neurotransmission, through
      ET(B) receptor mechanisms.

PMID- 9023306
TI  - Common quantitative trait loci for alcohol-related behaviors and central nervous
      system neurotensin measures: hypnotic and hypothermic effects.
AB  - Genetic correlations were found between high-affinity neurotensin receptor
      (NTR(H)) densities and NT-immunoreactivity (NT-ir) levels in specific brain
      regions and sensitivity to hypnotic and hypothermic effects of ethanol in LSXSS
      recombinant inbred strains of mice. Simple sequence length polymorphisms were
      used to identify quantitative trait loci (QTL) influencing hypnotic and
      hypothermic sensitivity to ethanol, NTR(H) and low-affinity neurotensin receptor
      densities and NT-ir levels in LSXSS recombinant inbred strains. Common QTL for
      NTR(H) receptor densities, NT-ir levels and these ethanol actions were
      identified. One of the QTL (chromosome 2, 80 cM) for NTR(H) density and hypnotic
      sensitivity is linked to the NTR(H) gene, Ntsr. Also, QTL for NTR(H) density were
      found in common with confirmed QTL for hypnotic sensitivity on chromosomes 1 (43
      cM), 11 (57 cM) and 15 (56 cM) and with an unconfirmed QTL on chromosome 3 (19
      cM). Two common QTL for NT-ir levels, but not NTR(H) or low-affinity neurotensin
      receptor receptors, and ethanol-induced hypothermia were observed on chromosomes
      4 (43 cM) and 6 (41 cM). Two common QTL for NT-ir levels and sleep time were
      identified on chromosomes 3 (19 cM) and 9 (55 cM). Common QTL indicate that genes
      regulating NT receptor and/or NT-ir expression may be the same as those
      regulating sensitivity to ethanol.

PMID- 9023307
TI  - Common quantitative trait loci for alcohol-related behaviors and central nervous
      system neurotensin measures: locomotor activation.
AB  - We have analyzed LSXSS recumbinant inbred for ethanol-induced activity using 2.0
      g/kg ethanol and a new method we call ethanol activation slope. The ethanol
      activation slope provides a robust dose-response measure of ethanol activation,
      independent of both activity after saline and the inhibitory effects of ethanol
      on locomotor activity. These behavioral data were used in a quantitative trait
      locus analysis to map chromosomal loci involved in ethanol-induced locomotor
      activity. We tentatively identified seven loci that mediate the low-dose
      stimulatory effect of ethanol and six loci involved in locomotion after 2.0 g/kg
      ethanol. Only one of the loci are in common between the two behaviors. We also
      compared the behavioral quantitative trait locus to those previously identified
      that are involved in regulating central nervous system neurotensin levels and
      neurotensin receptor densities. Six chromosomal regions were identified that
      regulate at least one central nervous system neurotensin measure and an ethanol
      induced locomotor behavior. The identification of loci controlling both central
      nervous system neurotensin levels or neurotensin receptor densities and ethanol
      induced locomotor activity strengthens the proposal that neurotensin regulates,
      in part, ethanol-induced behaviors and central nervous system sensitivity to
      ethanol.

PMID- 9023308
TI  - Identification of cytochrome P450 isoforms involved in citalopram N-demethylation
      by human liver microsomes.
AB  - Studies to assess the enzyme kinetic behavior and to identify the cytochrome P450
      (CYP) isoform(s) involved in the major metabolic pathway (N-demethylation) for
      citalopram (CIT), a selective serotonin reuptake inhibitor, were performed using
      human liver microsomes and cDNA-expressed human cytochrome P450 isoforms. The N
      demethylation activities showed significant correlations with the alpha- and 4
      hydroxylation activities of triazolam (r(s) = 0.818 and 0.851, respectively; P <
      .01) in 10 different human liver microsomes. Anti-CYP3A antibodies and
      ketoconazole strongly inhibited CIT N-demethylation. In addition, there was a
      significant correlation between CIT N-demethylation and (S)-mephenytoin 4'
      hydroxylation (r(s) = 0.773, P < .05), although little inhibition was observed in
      the presence of anti-CYP2C antibodies or (S)-mephenytoin. cDNA-expressed CYP3A4
      and CYP2C19 catalyzed CIT N-demethylation, whereas no appreciable activities were
      observed for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6 and CYP2E1. The percentage
      contributions of CYP3A4 and CYP2C19 to the overall N-demethylation of CIT in
      human liver microsomes were estimated using a relative activity factor;
      respective values of 70% and 7% were calculated for microsomes obtained from
      livers from putative extensive metabolizers for (S)-mephenytoin 4'-hydroxylation.
      These results suggest that CYP3A4 is the major isoenzyme and CYP2C19 is the minor
      form involved in the major metabolic pathway for CIT in human liver microsomes.

PMID- 9023309
TI  - Naloxone-reversible antinociception by paracetamol in the rat.
AB  - Paracetamol at the dose of 400 mg/kg i.p. displayed antinociceptive activity in
      the hot-plate test and the formalin test. Moreover, it induced a significant
      increase in brain serotonin (5-HT) concentration and a reduction in the number of
      5-HT2 receptors in cortical membranes. Pretreatment with naloxone abolished this
      antinociceptive activity both in the hot-plate test and in the first phase of the
      formalin test without affecting the serum concentration of paracetamol. At the
      same time, naloxone prevented the increase in 5-HT concentration in the central
      nervous system and the reduction in 5-HT2 receptors in cortical membranes.
      Competition experiments demonstrated that paracetamol possesses affinity for
      [3H]naloxone binding sites. The action of morphine on nociception and on the
      serotonergic system was similar to that of paracetamol; all morphine-induced
      effects were blocked by naloxone. These data provide further evidence for a
      central antinociceptive effect of paracetamol and support the hypothesis that
      paracetamol exerts its antinociceptive activity through the serotonergic system.
      Moreover, our results point to the relationship between serotonergic and
      opiatergic systems in the antinociceptive activity of paracetamol.

PMID- 9023310
TI  - Nitric oxide and the neurotoxic effects of methamphetamine and 3,4
      methylenedioxymethamphetamine.
AB  - The role of nitric oxide (NO) in the long-term, amine-depleting effects of
      methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) was
      investigated in the rodent central nervous system. The NO synthase inhibitor N(G)
      nitro-L-arginine methyl ester (L-NAME) antagonized the dopamine- and serotonin
      depleting effects of both METH and MDMA. The protective actions of L-NAME in METH
      treated mice were reversed by prior administration of the NO generator isosorbide
      dinitrate. However, pretreatment with N(G)-monomethyl-L-arginine or N(G)-nitro-L
      arginine, two other NO synthase inhibitors, failed to block the neurotoxic
      effects of METH or MDMA. L-NAME was also the only NO synthase inhibitor that
      antagonized the hyperthermic effects of METH, reducing colonic temperatures in
      mice by a mean of 3 degrees C, in comparison with control. Moreover, if the
      hypothermic effects of L-NAME in METH-treated mice were prevented by raising the
      ambient room temperature, the dopamine-depleting actions of the stimulant were
      fully restored. The latter findings suggest that it is the hypothermic actions of
      L-NAME, rather than its NO inhibitory properties, that are responsible for the
      prevention of neurotoxicity. Together with the results of the N(G)-monomethyl-L
      arginine and N(G)-nitro-L-arginine experiments, the data suggest that NO plays
      little or no role in the toxic mechanism of action of METH or MDMA.

PMID- 9023311
TI  - Carrier-mediated active transport of the glucuronide and sulfate of 6-hydroxy-5,7
      dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) into rat liver:
      quantitative comparison of permeability in isolated hepatocytes, perfused liver
      and liver in vivo.
AB  - The hepatic uptake of glucuronic acid and sulfate conjugates of 6-hydroxy-5,7
      dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040), a dual
      inhibitor of 5-lipoxygenase and thromboxane A2 synthetase, was investigated in
      rats. The biliary excretion clearance values for the glucuronide and the sulfate,
      obtained after i.v. administration of E3040, were similar and corresponded to
      approximately 30% of the hepatic blood flow rate. The influx clearance values of
      E3040 conjugates in the presence of 3% bovine serum albumin, measured by a
      multiple indicator dilution method in the perfused liver, were 1.20 ml/min/g
      liver for the glucuronide and 0.74 ml/min/g liver for the sulfate, which were
      twice and equal to the normal hepatic plasma flow rate, respectively, which
      suggests the presence of an efficient transport system(s). The uptake of E3040
      conjugates into the isolated hepatocytes is mediated by Na(+)-independent active
      transport system(s), which is inhibited by dibromosulfophthalein and bile acids.
      The uptake for the sulfate had high-affinity and high-capacity transport activity
      (Km = 25 microM; Vmax = 7.8 nmol/min/10(6) cells) compared with that for the
      glucuronide (Km = 59 microM; Vmax = 2.2 nmol/min/10(6) cells). The uptakes of
      E3040 conjugates (glucuronide, sulfate) exhibited a mutual competitive
      inhibition. It is suggested that both conjugates share a multispecific organic
      anion transporter located on the sinusoidal membrane.

PMID- 9023312
TI  - Nonpeptide endothelin receptor antagonists. IX. Characterization of endothelin
      receptors in guinea pig bronchus with SB 209670 and other endothelin receptor
      antagonists.
AB  - In this study the endothelin (ET) receptors mediating contractions produced by ET
      1, ET-3 and the selective ET(B) ligands sarafotoxin 6c (S6c) and BQ-3020 in
      guinea pig bronchus were investigated using SB 209670, a nonpeptide, mixed
      ET(A)/ET(B) receptor antagonist, and the peptide ET receptor antagonists BQ-123
      (ET(A) receptor-selective), BQ-788 (ET(B) receptor-selective) and RES-701 (ET(B)
      receptor-selective). SB 209670 (10 microM) antagonized concentrations induced by
      ET-1 (pK(B) = 6.1). In contrast, BQ-788 (10 microM) and BQ-123 (10 microM),
      either alone or in combination, were without significant effect on ET-1
      concentration-response curves. SB 209670 (10 microM) and BQ-788 (10 microM)
      antagonized S6c concentration-response curves with pKB values of 6.6 and 5.5,
      respectively, whereas RES-701 (10 microM) and BQ-123 (10 microM) were without
      effect. SB 209670 (10 microM) was about a 10-fold less potent antagonist of
      contractions produced by ET-3 (pK(B) = 5.4) than of those elicited by S6c. BQ-788
      (10 microM), RES-701 (10 microM) and BQ-123 (10 microM) were without effect on ET
      3 concentration-response curves. BQ-788 (10 microM) had similar potencies for
      inhibition of contractions induced by S6c (pK(B) = 5.8) and BQ-3020 (pK(B) =
      6.25). These data indicate that contractions induced by ET-1, ET-3, S6c and BQ
      3020 in guinea pig bronchus appear to be mediated predominantly via stimulation
      of ET(B) receptors. However, these receptors are not very sensitive to the
      standard ET(B) receptor antagonists BQ-788 and RES-701, which suggests that
      responses produced by these ligands in this tissue involve activation not of the
      classical ET(B) receptor, but rather of an atypical ET receptor population. The
      results also provide additional evidence that the potencies of ET receptor
      antagonists depend upon the specific ET agonist.

PMID- 9023313
TI  - Biotransformation of parathion in human liver: participation of CYP3A4 and its
      inactivation during microsomal parathion oxidation.
AB  - Studies in rat liver have shown that cytochrome P450 (CYP) enzymes mediate the
      oxidative biotransformation of the phosphorothioate pesticide parathion to
      paraoxon and 4-nitrophenol. Transfer of the phosphorothioate thionosulfur atom to
      the CYP apoprotein results in amino acid modification and enzyme inactivation.
      Our study investigated the role of human hepatic CYP in parathion oxidation and
      their relative susceptibilities to inhibition and inactivation. Rates of
      parathion oxidation varied about 10-fold in microsomes from 23 individual livers
      (1.72-18.33 nmol total metabolites/mg protein/min). Linear regression of rates of
      parathion oxidation with those of other microsomal CYP reactions implicated
      CYP3A4 in the reaction. Thus, parathion oxidation was correlated strongly with
      testosterone 6beta-hydroxylation (r2 = 0.95, n = 11), but not with activities
      mediated by CYP 1A2, 2C9 or 2E1. CYP 3A4 expressed in lymphoblastoid cell lines
      was an efficient catalyst of parathion oxidation, although CYP 1A2 and 2B6 also
      catalyzed the activity. The CYP3A4 inhibitors ketoconazole and
      triacetyloleandomycin decreased the observed rate of microsomal parathion
      oxidation, but chemicals known to interact preferentially with other human CYP
      were essentially noninhibitory. P450 was lost during parathion biotransformation
      in human hepatic microsomes. Thus, incubation (10 min) of parathion (25 microM)
      with NADPH-supplemented microsomes led to an apparent 19 +/- 4% decrease in holo
      P450 content. Several CYP-specific oxidation reactions were inhibited and
      inactivated by parathion. Testosterone 6beta-hydroxylation (mediated by CYP3A4),
      7-ethylresorufin O-deethylation (CYP1A2) and tolbutamide methyl hydroxylation
      (CYP2C9/10), but not aniline 4-hydroxylation (CYP2E1), were inhibited effectively
      by parathion. Preincubation of microsomes with parathion and NADPH intensified
      the extent of inhibition (i.e., elicited inactivation) of reactions mediated by
      3A4 and 1A2 and, to a lesser extent, 2C9. In summary, these findings strongly
      implicate CYP 3A4 as the principal catalyst of parathion oxidation in human
      liver, although other CYP may play a lesser role. During parathion oxidation
      CYP3A4 undergoes significant inactivation. In view of the role of this enzyme in
      the oxidation of many therapeutic agents, exposure to phosphorothioate pesticides
      may adversely affect drug elimination in humans.

PMID- 9023314
TI  - [3H]inositol polyphosphate metabolism in muscarinic cholinoceptor-stimulated
      airways smooth muscle: accumulation of [3H]inositol 4,5 bisphosphate via a
      lithium-sensitive inositol polyphosphate 1-phosphatase.
AB  - Agonist-stimulated phosphoinositide hydrolysis is the principal mechanism
      underlying pharmacomechanical coupling in airways smooth muscle. In bovine
      tracheal smooth muscle, activation of muscarinic cholinoceptors results in
      sustained phospholipase C-mediated PtdIns(4,5)P2 hydrolysis but transient
      Ins(1,4,5)P3 accumulation, which implies agonist-stimulated metabolism of
      Ins(1,4,5)P3. To investigate the metabolic fate of Ins(1,4,5)P3 in bovine
      tracheal smooth muscle, we developed a [3H]inositol-labeling protocol wherein
      more than 98% of the [3H]inositol polyphosphates that accumulated over a 0 to 30
      min incubation with 100 microM carbachol in the presence of 5 mM LiCl were
      derived from [3H]Ins(1,4,5)P3 and wherein the Ins(1,4,5)P3 3-kinase (EC
      2.7.1.127) and 5-phosphatase (EC 3.1.3.56) pathways generated a set of mutually
      exclusive [3H]-inositol polyphosphate isomers. Under these conditions, the 5
      phosphatase pathway was shown to be the dominant route for [3H]Ins(1,4,5)P3
      metabolism at all time intervals measured, especially at early times (0-300 sec),
      where it accounted for more than 85% of [H]Ins(1,4,5)P3 metabolism. We also
      observed accumulation of a novel agonist and LiCl-sensitive [3H]InsP2 isomer
      identified as [3H]Ins(4,5)P2. The presence of a LiCI-sensitive inositol
      polyphosphate 1-phosphatase (EC 3.1.3.57) was demonstrated, and high LiCl
      concentrations (30 mM) caused a significant enhancement of [3H]Ins(1,4)P2
      accumulation and a corresponding decline in [3H]Ins4P levels. Because nearly
      identical bell-shaped LiCl concentration-response curves were obtained for
      [H]Ins4P and [3H]Ins(4,5)P2 accumulation, and [3H]Ins(4,5)P2 was not generated
      under conditions expected to stimulate phospholipase D, these data suggest that
      the most likely precurser of [3H]Ins(4,5)P2 is [3H]Ins(1,4,5)P3. This is the
      first demonstration of Ins(4,5)P2 accumulation in a non-neuronal cell type, and
      the foregoing data suggest a novel route of formation via an Ins(1,4,5)P3 1
      phosphatase, which would represent an additional pathway for [H]Ins(1,4,5)P3
      removal.

PMID- 9023315
TI  - Pharmacokinetic-pharmacodynamic contributions to the convulsant activity of
      pefloxacin and norfloxacin in rats.
AB  - The purpose of this investigation was to compare the convulsant activity of two
      quinolones differing, respectively, by the presence (pefloxacin) or absence
      (norfloxacin) of a methyl group on the piperazine moiety at the position 7 of
      their parent nuclei and consequently by their lipophilicity. An in vivo model was
      used, which can distinguish between ease in reaching pharmacological receptors at
      the central nervous system level, and ability to interact with these receptors.
      Male Sprague-Dawley rats (approximately 230g-300g) received an i.v. infusion of
      pefloxacin or norfloxacin at one of four different rates: 480, 960, 1440 and 1920
      micromol/hr, until the onset of maximal seizures. This occurred after an average
      of 12.7 to 69.4 min. We found enough evidence to suggest that in these conditions
      the contribution of pefloxacin metabolites, including norfloxacin, to its
      convulsant activity was negligible. Doses of pefloxacin and concentrations in
      cerebrospinal fluid and plasma (total and unbound) at the pharmacodynamic
      endpoint were all independent of infusion rate, whereas only cerebrospinal fluid
      concentrations of norfloxacin were independent of infusion rate. The overall
      cerebrospinal fluid concentration of norfloxacin (47.3 +/- 9.9 micromol/liter)
      was about 8-fold lower than that of pefloxacin (380 +/- 27 micromol/liter),
      indicating that on average the "intrinsic convulsant activity" of norfloxacin is
      8-fold greater than that of pefloxacin. However, total doses of pefloxacin and
      norfloxacin at the onset of maximal seizures were in the same order of magnitude
      (1500-2000 micromol/kg), suggesting that the higher ability of the more
      lipophilic pefloxacin to reach central nervous system compensates for its lower
      intrinsic convulsant activity.

PMID- 9023316
TI  - An ICAM-1 antisense oligonucleotide prevents and reverses dextran sulfate sodium
      induced colitis in mice.
AB  - Mice treated p.o. with 5% dextran sodium sulfate develop a mild to moderate
      colitis characterized by focal areas of inflammation and crypt abscesses.
      Immunohistological analysis of colons from dextran sodium sulfate-treated mice
      revealed an increased expression of intercellular adhesion molecule 1 (ICAM-1)
      and infiltration of lymphocyte function antigen 1-positive cells. A murine
      specific antisense oligonucleotide, ISIS 3082, was used to determine the role of
      ICAM-1 expression in the development of colitis. Prophylactic treatment of
      dextran sodium sulfate-treated mice with ISIS 3082 reduced the clinical signs of
      colitis in a dose-dependent manner, with maximal effects occurring at a dose of 1
      mg/kg/day. Reductions in ICAM-1 immunostaining and infiltrating leukocytes were
      observed in colons of animals treated with 1 mg/kg ISIS 3082. Scrambled control
      oligonucleotides failed to modify the course of the disease. The ICAM-1
      oligonucleotide also diminished the clinical severity of colitis in mice with
      established colitis. The toxicity of ISIS 3082 was assessed in normal CD-1 mice
      by administering the oligonucleotide intravenously every other day for 2 weeks.
      At pharmacologically relevant doses of ISIS 3082 (1 and 10 mg/kg), there were no
      signs of toxicity with respect to body and organ weights, clinical chemistry or
      hematology. At a dose of oligonucleotide 20- to 100-fold greater than maximal
      pharmacological doses, the oligonucleotide produced an increase in liver and
      spleen weights; a mild chronic inflammation in liver, lung and lymph nodes;
      monocytosis and an elevation of serum liver transaminases. These data suggest
      that an antisense oligonucleotide that reduces ICAM-1 expression could be
      effective in the therapy of inflammatory bowel disease in humans and that such an
      oligonucleotide would be safe at pharmacologically relevant doses.

PMID- 9023317
TI  - Slow-release clodronate in prevention of inflammation and bone loss associated
      with adjuvant arthritis.
AB  - The effects of slow-release calcium clodronate on rat adjuvant arthritis were
      investigated using two different dosing schedules. In prophylactic treatment,
      calcium clodronate was given on the same day as the adjuvant injection, and in
      therapeutic treatment, calcium clodronate administration was delayed until the
      animals had active disease, to day 14 postadjuvant. Calcium clodronate was given
      as single i.m. injections into the thigh muscles. Arthritis index, histopathology
      of hindpaw, quantitative histomorphometry, bone mineral density and serum
      osteocalcin, alkaline phosphatase and calcium were studied. Calcium clodronate
      given therapeutically decreased the severity of paw swelling slightly more than
      prophylactic treatment, a result seen as lower scores of arthritis index.
      Histopathological evaluation of hindpaws showed that calcium clodronate protected
      against inflammation-induced bone loss and reactive bone formation in the
      hindpaw, but not against inflammatory changes involving articular cartilage.
      Quantitative histomorphometric analysis of the distal femur indicated that
      trabecular bone area was decreased by 86% in arthritic rats compared with normal
      untreated controls. Both the prophylactic and the therapeutic treatment with
      calcium clodronate prevented this osteopenia (P < .001). Bone mineral density
      measured by computed tomography was also significantly reduced in distal femoral
      metaphysis in adjuvant arthritic rats, but restoration to virtually normal values
      occurred with calcium clodronate (P < .001). In both dosing schedules, we
      observed a suppression of arthritis, which was associated with a decrease in paw
      swelling and an inhibition of the severe osteopenia in the distal femoral
      metaphysis. The long duration of action after a single injection of calcium
      clodronate indicates that the insoluble salt remains at the injection site and is
      released slowly into the bloodstream.

PMID- 9023318
TI  - The effect of inhibitors of inducible nitric oxide synthase on chronic colitis in
      the rhesus monkey.
AB  - GI inflammation is associated with an increase in nitric oxide production and
      expression of the inducible isoform of nitric oxide synthase (iNOS). Using a
      spontaneous model of chronic colonic inflammation in rhesus monkeys, which shares
      morphological and clinical features with ulcerative colitis, we assessed the
      therapeutic benefit of administration of iNOS inhibitors. Sixteen colitic rhesus
      monkeys underwent an endoscopy procedure before commencement of the trial, and
      biopsies from three sites of the colon and plasma were collected. Monkeys were
      randomly assigned to three treatment groups and were administered by oral bolus
      60 mg/kg/day L-N 6-(1-Iminoethyl) lysine, 60 mg/kg/day aminoguanidine or a
      placebo (0.9% NaCl) twice daily. Monkeys were sacrificed after 10 days, coIonic
      tissue from multiple sites was dissected and processed for histological and
      biochemical analysis. In rhesus colitis, diarrhea was characterized by a
      significant increase in fecal water content and daily fecal output. iNOS was
      localized immunohistochemically in plasma cells and neutrophils in the colonic
      mucosa and lamina propria, paralleled by enhanced iNOS gene expression determined
      by reverse-transcriptase polymerase chain reaction. Only L-N 6-(1-iminoethyl)
      lysine administration resulted in a significant reduction in systemic nitric
      oxide production, and neither of the iNOS inhibitors significantly reduced the
      histological inflammatory score nor ameliorated diarrheal symptoms. From these
      findings, we conclude that in this chronic, spontaneous model of colonic
      inflammation, administering iNOS inhibitors with this treatment regimen did not
      provide any major therapeutic benefit.

PMID- 9023319
TI  - Self-injurious behavior and dopaminergic neuron system in neonatal 6
      hydroxydopamine-lesioned rat: 1. Dopaminergic neurons and receptors.
AB  - Dopaminergic neuronal circuits underlying self-injurious behavior (SIB) were
      investigated in neonatal 6-hydroxydopamine (6-OHDA)-induced dopamine-depleted
      rats. The extent of damaged dopamine neuronal areas was investigated by
      quantitative analysis of tyrosine hydroxylase (TH) immunocytochemistry and the
      biochemical quantification of dopamine levels in three groups; neonatal 6-OHDA
      treated rats showing SIB (the SIB(+) group), neonatal 6-OHDA-treated rats not
      showing SIB (SIB(-) group) and neonatal saline-treated controls (control group).
      In the SIB(+) group, both dorsal and ventral mesostriatal dopaminergic neuron
      systems were severely destroyed, but the mesocortical dopaminergic neuron system
      and intrahypothalamic dopaminergic neuron system remained intact. In SIB(-)
      group, the dorsal mesostriatal dopaminergic neuron system was severely destroyed,
      but the ventral mesostriatal dopaminergic neuron system was only partially
      impaired. The effect of neonatal 6-OHDA treatment on dopaminergic receptors was
      analyzed by quantitative in vitro receptor autoradiography using [3H]SCH-23390
      for the D1 site and [3H]YM-09151-2 for the D2 site. Although D1 and D2 binding
      was not altered in the dorsal and ventral striatum, cerebral cortex and
      hypothalamus, the D1 binding in the substantia nigra pars reticulata was
      increased in the SIB(+) group compared with the SIB(-) or control groups. The D1
      binding assay using the membrane preparation of the nigral homogenates, revealed
      that the KD did not change, but the Bmax in the SIB(+) group was higher than that
      in the SIB(-) or control groups (P < .05). These results suggest that the region
      specific change of dopaminergic neurons and receptors underlies the manifestation
      of SIB.

PMID- 9023320
TI  - Self-injurious behavior and dopaminergic neuron system in neonatal 6
      hydroxydopamine-lesioned rat: 2. Intracerebral microinjection of dopamine
      agonists and antagonists.
AB  - Intracisternal 6-hydroxydopamine treatment to newborn rats caused massive and
      permanent damage of brain dopaminergic neurons, and many of these animals show
      self-injurious behavior (SIB) when loaded by systemic injection of L
      dihydroxyphenuylalanine (L-DOPA) or D1 agonist, SKF-38393. SIB occurred at life
      long time in neonatal 6-hydroxydopamine-lesioned rats, because SIB confirmed rats
      at 4 to 6 wk all showed SIB at 3 to 5 mo and at 12 to 13 mo after L-DOPA loading.
      To elucidate the brain locus important for the induction and cessation of SIB, in
      our study, we microinjected dopamine agonists and antagonists into various
      dopamine neuron innervating areas. L-DOPA-induced SIB was inhibited by the
      injection of a D1 antagonist, SCH-23390 (5 microg), into the bilateral substantia
      nigra, but not into the bilateral caudate-putamen or nucleus accumbens. The
      microinjection of YM-09151-2 (10 microg), a D2 antagonist, into these regions
      could not stop SIB. For examining the important area for the induction of SIB, we
      microinjected SKF-38393, D1 agonist, and/or LY-141865, D2 agonist (each 1 microg)
      into bilateral (or ipsilateral) caudate-putamen and substantia nigra. SIB was
      induced only in the case of D1 and D2 receptors in both the bilateral caudate
      putamen and bilateral substantia nigra being stimulated simultaneously by the
      mixed application of SKF-38393 and LY-141865. SIB was not induced by the sole
      injection of SKF-38393 into bilateral caudate-putamen or bilateral substantia
      nigra. These observations suggest that both caudate-putamen and nigral D1- and D2
      like receptors are important for the induction of SIB, but, for cessation of SIB,
      up-regulated nigral D1 receptor is crucial.

PMID- 9023321
TI  - The long-acting parenteral iron chelator, hydroxyethyl starch-deferoxamine, fails
      to protect against alcohol-induced liver injury in rats.
AB  - We studied the effect of the long-acting parenteral iron chelator, hydroxyethyl
      starch deferoxamine (HES-DFO) on liver nonheme iron, lipid peroxidation and
      pathologic changes in the liver in the intragastric feeding rat model for
      alcoholic liver disease. Male Wistar rats (225-250 g) were fed liquid diet and
      ethanol for 2 months. In control pair-fed animals, ethanol was isocalorically
      replaced by dextrose. Two additional groups of animals (dextrose and ethanol fed)
      received HES-DFO (25 mg deferoxamine equivalents/kg, three times a week). The
      blood ethanol level in the ethanol-fed animals was maintained between 150 and 350
      mg/dl. For each animal, the levels of hepatic nonheme iron, lipid peroxidation
      and pathologic changes were evaluated. Ethanol administration caused fatty liver,
      necrosis and inflammation. Addition of HES-DFO to the ethanol diet increased the
      severity of pathologic changes, particularly necrosis and inflammation. The
      nonheme iron in alcohol-fed animals was significantly higher (18.3 +/- 4.3 microg
      liver) than in pair-fed dextrose controls (12.5 +/- 1.5 microg, P < .05).
      Addition of HES-DFO significantly increased nonheme iron levels in the dextrose
      fed rats (17.1 +/- 2.0 microg/g, P < .02) but not in ethanol-fed rats (20.0 +/-
      2.0). Ethanol increased levels of conjugated dienes; these levels were not
      altered by HES-DFO. The most significant observations in this study were: 1) the
      higher hepatic nonheme iron content in ethanol-fed rats compared with pair-fed
      dextrose controls; 2) the absence of changes in hepatic nonheme iron levels or
      lipid peroxidation in ethanol-fed groups treated with HES-DFO; and 3) the
      worsening of liver injury in ethanol-fed rats by HES-DFO.

PMID- 9023322
TI  - Evidence that the organic cation/H+ exchanger in the brush border membrane of dog
      kidney is a 41-kDa protein.
AB  - Organic cation (OC+)/H+ exchangers are found in several mammalian tissues and in
      numerous organisms. In the kidney OC+/H+ exchange activity is localized to the
      brush border membrane of the proximal tubule cells of the nephron and is believed
      to be responsible for the efflux of numerous xenobiotics from the tubule cell
      into the tubular fluid. The objective of the present study was to identify the
      OC+/H+ exchanger in brush border membrane vesicles isolated from dog kidney by
      photoaffinity labeling. The results show that [3H]azidopine is an ideal
      photoaffinity labeling reagent; in the dark it binds reversibly, but irreversibly
      after photoactivation. The photoaffinity labeling reaction is efficient, specific
      and sensitive. Our findings are consistent with the conclusions that a 41-kDa
      protein is the exchanger and that it is present at a concentration of 780 +/- 140
      fmol/mg membrane protein (n = 4). A 49-kDa protein is labeled to some extent as
      well. The relationship between the 41- and 49-kDa proteins has not been resolved.

PMID- 9023323
TI  - Distribution of clodronate in the bone of adult rats and its effects on
      trabecular and cortical bone.
AB  - Distribution of clodronate in cancellous and cortical bone of the femur and in
      cancellous bone of lumbar vertebrae in adult rats was examined by means of
      quantitative autoradiography. In addition, the effects of clodronate on
      cancellous and cortical bone were evaluated by bone histomorphometry. Six-month
      old male rats were given a mixture of unlabeled and 14C-labeled disodium
      clodronate subcutaneously on 5 consecutive days at cumulative doses of 125 mg/50
      microCi/kg or 250 mg/100 microCi/kg and followed up for 2, 23 or 79 days after
      the last dose. The highest activity of 14C-clodronate was found in the primary
      spongiosa of the distal femoral metaphysis and in the cortical bone of the
      femoral diaphysis. Radioactivity in the lumbar vertebra was found to be about
      half of that in the femur. No marked decrease in radioactivity was found in bone
      specimens taken after the follow-ups. In these specimens, however, labeled
      clodronate originally incorporated into the primary spongiosa was situated
      further away from the growth plate because of longitudinal bone growth. A cross
      section of the femoral shaft showed that incorporation of clodronate was more
      prominent into the periosteal surface than into the endocortical surface. No
      marked histological effects were seen, except for an increase in the mineralized
      hard tissue area in the primary spongiosa of the distal femur.

PMID- 9023324
TI  - Tolerance to mu-opioid receptor agonists but not cross-tolerance to gamma
      aminobutyric acid(B) receptor agonists in arcuate A12 dopamine neurons with
      chronic morphine treatment.
AB  - The present study examined the potential for cross-tolerance development between
      mu-opioid and gamma-aminobutyric acidB receptor agonists, in hypothalamic arcuate
      neurons, resulting from chronic morphine treatment. Intracellular recordings were
      made in hypothalamic slices prepared from ovariectomized female guinea pigs. The
      mu-opioid receptor agonist D-Ala2,N-Me-Phe4,Gly-ol5-enkephalin and the gamma
      aminobutyric acidB receptor agonist baclofen produced dose-dependent membrane
      hyperpolarizations of arcuate neurons. The reversal potential for both agonist
      induced hyperpolarizations was near -95 mV, indicative of the activation of an
      underlying K+ conductance. Coadministration of maximally effective concentrations
      of D-Ala2,N-Me-Phe4,Gly-ol5-enkephalin and baclofen produced a response that was
      not additive, indicating a convergence onto a common K+ channel. In arcuate
      neurons, including a subset that was immunopositive for tyrosine hydroxylase,
      chronic morphine treatment for 4 to 7 days produced a 3.2-fold reduction in the
      potency, with no change in the efficacy, of D-Ala2,N-Me-Phe4,Gly-ol5-enkephalin.
      In contrast, it affected neither the potency nor the efficacy of baclofen.
      Therefore, chronic morphine exposure does not produce cross-tolerance between mu
      opioid and gamma-aminobutyric acidB receptor agonists in A12 dopamine neurons,
      suggesting that convergence upon a common effector is not a sufficient criterion
      for the development of cross-tolerance between receptor systems.

PMID- 9023326
TI  - Effects of cyclosporine or FK506 in chronic colitis.
AB  - The objective of this study was to quantitatively characterize the effects FK506
      on the pathophysiology observed in a model of chronic granulomatous colitis in
      rats and compare these effects to those obtained with cyclosporin A (CyA).
      Chronic granulomatous colitis was induced in female Lewis rats via intramural
      (subserosal) injections of peptidoglycan/polysaccharide (PG/PS) into the distal
      colon. Rats then received daily injections (i.m.) of either vehicle for CyA (0.5
      ml/kg cremophor), CyA in vehicle (25 mg/kg), saline (0.5 ml/kg) or FK506 (1 mg/kg
      in saline), beginning 7 days after PG/PS injection and continuing for an
      additional 2 weeks. On day 21, we found that the intramural injection of PG/PS
      produced a chronic colitis that was associated with hepatic and splenic
      granulomatous inflammation. Daily treatment with CyA or FK506 beginning 7 days
      after the induction of colitis resulted in significant inhibition in colonic
      mucosal permeability, colonic myeloperoxidase activity and plasma nitrate/nitrite
      levels when compared with their vehicle or untreated controls. In some instances,
      we noticed a significant vehicle-dependent anti-inflammatory activity. The
      incidence of peritoneal adhesions as well as the presence of hepatic and splenic
      granulomas induced by PG/PS were also significantly reduced in both the CyA- and
      FK506-treated groups. Taken together, these data suggest that immunosuppressive
      therapy is effective at attenuating both the colitis as well as the
      extraintestinal inflammation induced by PG/PS. We conclude that FK506 may be
      useful in the treatment of certain types of inflammatory bowel disease.

PMID- 9023325
TI  - Induction of prostaglandin H synthase-2 and tumor necrosis factor-alpha in human
      amnionic WISH cells by various stimuli occurs through distinct intracellular
      mechanisms.
AB  - These studies examined the signal transduction mechanisms by which prostaglandin
      (PG) E2 production can occur in human amnionic WISH cells in response to the
      stimuli okadaic acid, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha,
      phorbol-12-myristate-13-acetate (PMA) or combinations of PMA with IL-1beta or TNF
      alpha. We also investigated whether WISH cells are capable of producing TNF-alpha
      or IL-1beta in response to stimulation, because these cytokines can be produced
      in an autocrine fashion to perpetuate an inflammatory response. Our data indicate
      that the magnitude of PGE2 production induced by a given stimulus correlated
      temporally with the level of PGH synthase-2 (PGHS-2) protein. PMA or IL-1beta
      induced PGE2 production 2 to 4 hr after treatment, whereas the combination of
      these agents produced the most rapid induction 2 hr after treatment. Only okadaic
      acid induced the production of both PGE2 and TNF-alpha, after a lag of 12 to 18
      hr. PGE2 production by all stimuli was inhibited by dexamethasone, the IL-1
      receptor antagonist (IL-1ra), the specific PGHS-2 inhibitor NS-398 and the
      protein kinase inhibitor staurosporin. In contrast, TNF-alpha production in
      response to okadaic acid was inhibited by the TNF-converting enzyme inhibitor GI
      129471 and staurosporin but was unaffected by either IL-1ra, dexamethasone or NS
      398. We conclude that WISH cells are capable of producing bioactive
      proinflammatory mediators such as TNF-alpha and PGE2 through separable
      intracellular signal transduction mechanisms. The ability of IL-1ra to reduce
      PGE2 production caused by all stimuli used suggests an autocrine role for IL-1 in
      PGHS-2 induction in these cells.

PMID- 9023327
TI  - Oxidative stress regulates the expression and activity of transcription factor
      activator protein-1 in rat conceptus.
AB  - The transcription factor activator protein-1 (AP-1), composed of the Fos and Jun
      families of proto-oncogenes, is induced in response to extracellular signals as
      part of an immediate-early gene response. We hypothesize that teratogens such as
      oxidative stress induce AP-1 activity in the rat conceptus and that this AP-1
      response may either trigger abnormal development or protect the embryo against
      insult. To test this hypothesis, the AP-1 response was assessed in whole embryos
      in culture. There was a significant elevation in the oxidized to reduced
      glutathione ratio in the embryo and yolk sac within 0.25 hr of the initiation of
      culture, peaking at 0.5 hr; this is indicative of heightened oxidative stress. At
      0.5 hr protein oxidation was also enhanced, as demonstrated by increased protein
      reactivity with 2,4-dinitrophenylhydrazine. In the conceptus, the steady-state
      concentrations of c-fos, c-jun, junB and junD mRNAs were induced, peaking at 0.5
      hr and returning to base line by 1 to 2 hr in the embryo and by 1 to 6 hr in the
      yolk sac. Electrophoretic mobility shift assays showed enhanced AP-1 DNA-binding
      activity in both the embryo (elevated by 0.5 hr and persisting for 1 hr) and the
      yolk sac (persisting for 3 hr). Thus, there are tissue-specific differences in
      the duration of the AP-1 response in the conceptus. Addition of the antioxidants
      catalase and superoxide dismutase, but not vitamin E, prevented the rise in the
      oxidized to reduced glutathione ratio and also inhibited the induction of AP-1
      mRNAs and DNA-binding activity. The AP-1 response to oxidative stress may
      determine how the conceptus responds to insult.

PMID- 9023328
TI  - Glucocorticoids regulate the expression of adenosine A1 but not A(2A) receptors
      in rat brain.
AB  - The effect of adrenalectomy on the expression of adenosine receptors and their
      mRNA in rat brain was examined using quantitative autoradiography and in situ
      hybridization. 1,3-[3H]Dipropyl-8-cyclopentylxanthine ([3H]DPCPX), a selective
      adenosine A1 receptor antagonist, and [3H]CGS 21680, a selective adenosine A(2A)
      receptor agonist, were used as radioligands. One week after adrenalectomy, the
      expression of mRNA for adenosine A1 receptors was significantly decreased, as was
      the number of binding sites for [H]DPCPX. These effects were significantly
      counteracted by replacement treatment with dexamethasone (1.5 mg/kg i.p., twice
      daily). Addition of GTP caused a similar increase of [3H]DPCPX binding in sham
      operated rats, adrenalectomized rats and rats adrenalectomized and treated with
      dexamethasone. Moreover, no differences in displacement of [3H]DPCPX by the
      adenosine receptor agonist N6-(R-phenylisopropyl)adenosine were found among these
      groups. Adrenalectomy did not significantly affect the number of [3H]CGS 21680
      binding sites in striatum or the mRNA encoding adenosine A(2A) receptors. No
      changes in the affinity of [3H]CGS 21680 for adenosine A(2A) receptors or in the
      potency of the adenosine receptor agonist 2-chloroadenosine to displace [3H]CGS
      21680 were found. Dexamethasone treatment decreased cAMP formation induced by the
      nonselective adenosine agonist 5'-N-ethylcarboxamidoadenosine in Jurkat cells,
      which express adenosine A(2B) receptors, but did not alter it in PC-12 cells,
      which express mostly A(2A) receptors. The results suggest that endogenous
      corticosteroids positively regulate the expression of adenosine A1 receptors, at
      least partly at the transcriptional level. In contrast, corticosteroids do not
      regulate the expression of adenosine A(2A) receptors.

PMID- 9023329
TI  - Affinity and selectivity of PD156707, a novel nonpeptide endothelin antagonist,
      for human ET(A) and ET(B) receptors.
AB  - We have determined the affinity and selectivity of a new nonpeptide antagonist
      PD156707 (sodium 2-benzo(1,3ioxol-5-yl-4-(4-methoxy-pheny l)-4-oxo-3-(3,4,5-trime
      tho xybenzyl)-but-2-enoate) for human endothelin (ET)(A) and ET(B) receptors. In
      human coronary artery and saphenous vein the affinity of the ET(A) receptor for
      PD156707 was 0.15 +/- 0.06 nM and 0.5 +/- 0.13 nM, respectively. Competition
      experiments in human left ventricle and kidney revealed that PD156707 had 1,000-
      to 15,000-fold selectivity for the ET(A) receptor over the ET(B) receptor. This
      selectivity was confirmed autoradiographically. In human coronary artery, mammary
      artery and saphenous vein PD156707 (3-300 nM) potently antagonized the
      vasoconstrictor responses to ET-1. The pA2 values estimated from the Gaddum
      Schild equation were 8.07 +/- 0.09, 8.45 +/- 0.11 and 8.70 +/- 0.13,
      respectively. The concentration-response curves to ET-1 were shifted to the right
      in parallel fashion, without reduction of the maximum response. However, the
      regression lines fitted to the resulting Schild data deviated significantly from
      one. PD156707 appeared to be a more effective antagonist at lower concentrations
      than at the higher ones. It is possible that PD156707, a sodium salt, was
      reverting to a less soluble form which results in underestimation of its potency.
      These data show that PD156707 is a potent and selective antagonist at human ET(A)
      receptors and will be useful in clarifying the role of the endothelin peptides in
      human cardiovascular disease.

PMID- 9023330
TI  - Different B1 kinin receptor expression and pharmacology in endothelial cells of
      different origins and species.
AB  - In bovine aortic endothelial cells (BAECs), we previously demonstrated B1 and B2
      kinin receptor-mediated increases in intracellular guanosine-3',5'-cyclic
      monophosphate (cGMP). In this study, the B2 kinin receptor agonist bradykinin
      increased cGMP in rat microvascular coronary endothelial cells (RMCECs) and human
      umbilical vein endothelial cells (HUVECs), which could be prevented with the
      specific B2 kinin receptor antagonist icatibant but not with the B1 kinin
      receptor antagonist des-Arg9-[Leu8]bradykinin or with the nonpeptide kinin
      receptor antagonist WIN 64338. B2 kinin receptor mRNA could be detected in all
      three cell types using reverse transcription-polymerase chain reaction and
      subsequent Southern blotting. The B1 kinin receptor agonist des-Arg9-bradykinin
      increased cGMP in RMCECs but not in HUVECs. The response in RMCECs could be
      prevented by des-Arg9-[Leu8]bradykinin as well as by WIN 64338 but not by
      icatibant. In BAECs, the B1 kinin receptor-mediated cGMP synthesis could be
      prevented by icatibant and desensitized by preincubation with des-Arg9-bradykinin
      as well as bradykinin. We detected B1 kinin receptor mRNA in RMCECs and HUVECs
      but not in BAECs. In HUVECs, the detection of B1 kinin receptor mRNA is in
      contradiction to the cGMP measurements. In BAECs, the atypical B1 kinin receptor
      pharmacology, the heterologous desensitization of the receptor and the failure to
      detect B1 kinin receptor mRNA cannot be explained by a typical B1 kinin receptor
      subtype. Thus, B2 kinin receptors with similar pharmacology are constitutively
      expressed in each of the three endothelial cell types. However, the endothelial
      cell types are heterogeneous in the expression of typical B1 kinin receptors and
      the pharmacology of the B1 kinin receptor-mediated responses.

PMID- 9023331
TI  - SNAREs and regulated vesicle exocytosis.

PMID- 9023332
TI  - Scaling laws for fully developed turbulent flow in pipes: discussion of
      experimental data.
AB  - We compare mean velocity profiles measured in turbulent pipe flows (and also in
      boundary layer flows) with the predictions of a recently proposed scaling law; in
      particular, we examine the results of the Princeton "super-pipe" experiment and
      assess their range of validity.

PMID- 9023333
TI  - Structural correlations in protein folding funnels.
AB  - While the overall energy landscape of a foldable protein can be described by
      means of a few parameters characterizing its statistical topography, specific
      energetic terms subtly bias the representative structures giving rise to residue
      pair correlations as in a liquid. We use a free energy functional incorporating
      an inhomogeneous pair contact energy along with a contact formation entropy and a
      cooperativity contribution to determine residue-specific contact probabilities in
      the denatured state and the transition state ensemble. The predicted "hot
      residues" for the theoretical transition state ensemble reasonably agree with
      experiment for chymotrypsin inhibitor 2, and generally a strong correlation
      exists with the measured kinetic effects of mutating residues not involved in
      highly solvent-exposed regions.

PMID- 9023334
TI  - Geometrics of knowledge.
AB  - It is argued that knowledge representations formalized through pattern theoretic
      structures are geometric in nature in the following sense. The configurations and
      resulting patterns appearing in such representations exhibit invariances with
      respect to the similarity groups and are characterized topologically through
      their connection types. Starting with a special pattern from microbiology, it is
      shown how the basic pattern theoretic concepts are introduced in general and what
      their function is in representing knowledge. Variance/invariance of the patterns
      is discussed in geometric language. The measures on the configuration spaces are
      implemented by difference/differential equations which are used as a basis for
      computer algorithms.

PMID- 9023336
TI  - Hydrogen peroxide-mediated alteration of the heme prosthetic group of
      metmyoglobin to an iron chlorin product: evidence for a novel oxidative pathway.
AB  - Treatment of metmyoglobin with H2O2 is known to lead to the crosslinking of an
      active site tyrosine residue to the heme [Catalano, C. E., Y. S. Choe, and P. R.
      Ortiz de Montellano (1989) J. Biol. Chem. 264, 10534-10541]. We have found in
      this study that this reaction also leads to an altered heme product not
      covalently bound to the protein. This product was characterized by visible
      absorption, infrared absorption, and mass and NMR spectrometry as an iron chlorin
      product formed from the saturation of the double bond between carbon atoms at
      positions 17 and 18 of pyrrole ring D with concomitant addition of a hydroxyl
      group on the carbon atom at position 18 and lactonization of the propionic acid
      to the carbon atom at position 17. Studies with the use of (18)O-labeled H2O2,
      O2, and H2O clearly indicate that the source of the added oxygen on the heme is
      water. Evidently, water adds regiospecifically to a cationic site formed on a
      carbon atom at position 18 after oxidation of the ferric heme prosthetic group
      with peroxide. Prolonged incubation of the reaction mixture containing the iron
      hydroxychlorin product led to the formation of an iron dihydroxychlorin product,
      presumably from a slow addition of water to the initial iron hydroxychlorin. The
      iron chlorin products characterized in this study are distinct from the meso
      oxyheme species, which is thought to be formed during peroxide-mediated
      degradation of metmyoglobin, cytochrome P450, ferric heme, and model ferric
      hemes, and give further insight into the mechanism of H2O2-induced heme
      alterations.

PMID- 9023335
TI  - Transcriptional repression at a distance through exclusion of activator binding
      in vivo.
AB  - The yeast repressor Rme1p acts from distant binding sites to block transcription
      of the chromosomal IME1 gene. Rme1p can also repress the heterologous CYC1
      promoter when Rme1p binding sites are placed 250-300 bp upstream of CYC1
      transcriptional activator binding sites (UAS1 and UAS2). Here, in vivo
      footprinting studies indicate that Rme1p acts over this distance by preventing
      the binding of the CYC1 transcriptional activators to UAS1 and UAS2. Inhibition
      of activator binding by Rme1p has the same genetic requirements as repression:
      both depend upon sequences flanking the Rme1p binding sites and upon Rgr1p and
      Sin4p, two subunits of the RNA polymerase II-associated Mediator complex that are
      required for normal nucleosome density. Thus Rme1p may alter chromatin to prevent
      binding of transcriptional activators to distant DNA sequences.

PMID- 9023337
TI  - Binding of SecB to ribosome-bound polypeptides has the same characteristics as
      binding to full-length, denatured proteins.
AB  - The interaction of the chaperone SecB with ribosome-bound polypeptides that are
      in the process of elongation has been studied using an in vitro protein synthesis
      system. The binding is characterized by the same properties as those demonstrated
      for the binding of SecB to full-length proteins that are in nonnative
      conformation: it is readily reversible and has no specificity for the leader
      peptide. In addition, it is shown that the growing polypeptide chains must
      achieve a critical length to bind tightly enough to allow their isolation in
      complex with SecB. This explains the longstanding observation that, even when
      export is cotranslational, it begins late in synthesis. Furthermore, the required
      length is approximately the same as the length that defines the binding frame
      within denatured, full-length proteins bound to SecB.

PMID- 9023338
TI  - The activation process of the alpha1B-adrenergic receptor: potential role of
      protonation and hydrophobicity of a highly conserved aspartate.
AB  - In this study, a quantitative approach was used to investigate the role of D142,
      which belongs to the highly conserved E/DRY sequence, in the activation process
      of the alpha1B-adrenergic receptor (alpha1B-AR). Experimental and computer
      simulated mutagenesis were performed by substituting all possible natural amino
      acids at the D142 site. The resulting congeneric set of proteins together with
      the finding that all the receptor mutants show various levels of constitutive
      (agonist-independent) activity enabled us to quantitatively analyze the
      relationships between structural/dynamic features and the extent of constitutive
      activity. Our results suggest that the hydrophobic/hydrophilic character of D142,
      which could be regulated by protonation/deprotonation of this residue, is an
      important modulator of the transition between the inactive (R) and active (R*)
      state of the alpha1B-AR. Our study represents an example of quantitative
      structure-activity relationship analysis of the activation process of a G protein
      coupled receptor.

PMID- 9023339
TI  - Stochastic mechanisms in gene expression.
AB  - In cellular regulatory networks, genetic activity is controlled by molecular
      signals that determine when and how often a given gene is transcribed. In
      genetically controlled pathways, the protein product encoded by one gene often
      regulates expression of other genes. The time delay, after activation of the
      first promoter, to reach an effective level to control the next promoter depends
      on the rate of protein accumulation. We have analyzed the chemical reactions
      controlling transcript initiation and translation termination in a single such
      "genetically coupled" link as a precursor to modeling networks constructed from
      many such links. Simulation of the processes of gene expression shows that
      proteins are produced from an activated promoter in short bursts of variable
      numbers of proteins that occur at random time intervals. As a result, there can
      be large differences in the time between successive events in regulatory cascades
      across a cell population. In addition, the random pattern of expression of
      competitive effectors can produce probabilistic outcomes in switching mechanisms
      that select between alternative regulatory paths. The result can be a
      partitioning of the cell population into different phenotypes as the cells follow
      different paths. There are numerous unexplained examples of phenotypic variations
      in isogenic populations of both prokaryotic and eukaryotic cells that may be the
      result of these stochastic gene expression mechanisms.

PMID- 9023340
TI  - The Dr1/DRAP1 heterodimer is a global repressor of transcription in vivo.
AB  - A general repressor extensively studied in vitro is the human Dr1/DRAP1
      heterodimeric complex. To elucidate the function of Dr1 and DRAP1 in vivo, the
      yeast Saccharomyces cerevisiae Dr1/DRAP1 repressor complex was identified. The
      repressor complex is encoded by two essential genes, designated YDR1 and BUR6.
      The inviability associated with deletion of the yeast genes can be overcome by
      expressing the human genes. However, the human corepressor DRAP1 functions in
      yeast only when human Dr1 is coexpressed. The yDr1/Bur6 complex represses
      transcription in vitro in a reconstituted RNA polymerase II transcription system.
      Repression of transcription could be overcome by increasing the concentration of
      TATA-element binding protein (TBP). Consistent with the in vitro results,
      overexpression of YDR1 in vivo resulted in decreased mRNA accumulation.
      Furthermore, YDR1 overexpression impaired cell growth, an effect that could be
      rescued by overexpression of TBP. In agreement with our previous studies in
      vitro, we found that overexpression of Dr1 in vivo also affected the accumulation
      of RNA polymerase III transcripts, but not of RNA polymerase I transcripts. Our
      results demonstrate that Dr1 functions as a repressor of transcription in vivo
      and, moreover, directly targets TBP, a global regulator of transcription.

PMID- 9023341
TI  - The folding pathway of a protein at high resolution from microseconds to seconds.
AB  - We have documented the folding pathway of the 10-kDa protein barstar from the
      first few microseconds at the resolution of individual residues from its well
      characterized denatured state. The denatured state had been shown from NMR to
      have flickering native-like structure in the first two of its four alpha-helices.
      phi-value analysis shows that the first helix becomes substantially consolidated
      as the intermediate is formed in a few hundred microseconds, as does the second
      to a lesser extent. A native-like structure then is formed in a few hundred
      milliseconds as the whole structure consolidates. Peptide fragments corresponding
      to sequences containing the first two helices separately and together as a helix
      loop-helix motif have little helical structure under conditions that favor
      folding. The early stages of folding fit the nucleation-condensation model that
      was proposed for the smaller chymotrypsin inhibitor 2, which is a single module
      of structure and folds by two-state kinetics. The early stages of the multistate
      folding of the larger, multimodular, barnase have proved experimentally
      inaccessible. The folding pathway of barstar links those of CI2 and barnase to
      give a unified scheme for folding.

PMID- 9023342
TI  - Transient up-regulation of P2Y2 nucleotide receptor mRNA expression is an
      immediate early gene response in activated thymocytes.
AB  - In studies designed to understand the roles of P2 nucleotide receptors in
      differentiation of T lymphocytes, we observed a transient and protein synthesis
      independent enhancement of mRNA expression for the G protein-coupled P2Y2
      receptor in mouse thymocytes after the addition of steroid hormone or T cell
      receptor (TCR) crosslinking by anti-TCR mAb. Conversely, dexamethasone-induced
      increases in mRNA expression for the ligand-gated ion channel P2X1 receptor was
      detected in rat, but not mouse, thymocytes, raising questions about the
      previously suggested role of P2X1 receptors in thymocyte apoptosis. Flow
      cytometry analysis of thymocyte subsets excluded the possibility that the
      observed increases in P2Y2 receptor mRNA expression were due to the enrichment of
      steroid-treated cells with an P2Y2 mRNA-rich thymocyte subset. Triggering of TCR
      mediated intracellular signaling pathways through crosslinking of TCR or by
      addition of phorbol ester and Ca2+ ionophore also resulted in the up-regulation
      of P2Y2, but not P2X1, receptor mRNA. It is proposed that the rapid increase of
      P2Y2 receptor mRNA expression could be a common early event in responses of T
      cells to different activating stimuli. Taken together with the recently
      discovered ability of nucleotide receptor-initiated signaling to antagonize or
      enhance the effects of TCR crosslinking or steroids on thymocytes, the observed
      rapid up-regulation of P2Y2 receptor mRNA expression may reflect an immediate
      early gene response where newly expressed cell surface nucleotide receptors
      provide regulatory feedback signaling from extracellular ATP in the T cell
      differentiation process.

PMID- 9023343
TI  - Selective packaging of cargo molecules into endoplasmic reticulum-derived COPII
      vesicles.
AB  - Coated vesicles transport proteins from the endoplasmic reticulum (ER) to the
      Golgi apparatus. The formation of transport vesicles in vitro requires the
      incubation of an ER-membrane fraction with three protein fractions collectively
      known as coat protein II (COPII; Sar1p, Sec23p/Sec24p, and Sec13p/Sec31p). We
      used this assay to investigate how targeting [v-SNARE, vesicle-soluble NSF (N
      ethylmaleimide-sensitive factor) attachment protein receptor], putative adapter
      (e.g., Emp24p), and cargo molecules are captured into ER-derived COPII vesicles.
      Analysis of fusion proteins strongly suggests that the cytoplasmic domain of the
      v-SNARE protein Sec22p is required for its packaging into ER-derived COPII
      vesicles. We examined the packaging requirements for various molecules by
      individually titrating each of the COPII components. More Sar1p (the GTP-binding
      protein that initiates vesicles budding) is needed to package the membrane
      associated v-SNAREs and Emp24p than is needed to package the soluble secretory
      protein glycosylated pro-alpha-factor (gp alphaF). Microsomes prepared from a
      strain overproducing Sec12p (the nucleotide exchange protein that recruits Sar1p
      to the ER) produce vesicles containing gp alphaF without the addition of
      exogenous Sar1p, whereas the v-SNAREs and Emp24p are not efficiently packaged
      under these conditions. Addition of Sar1p to these microsomes leads to increased
      packaging of v-SNAREs and Emp24p with no increase in the packaging of gp alphaF.
      Finally, we show that membranes prepared from strains with mutations in the SEC16
      gene are more defective for the packaging of v-SNARE molecules and Emp24p than
      they are for the packaging of gp alphaF. These results point to the possibility
      that diverse signals or adapters participate in the capture of secretory and
      membrane cargo molecules into COPII transport vesicles.

PMID- 9023344
TI  - The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein
      phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic
      translation initiation factor 2 and preclude the shutoff of protein synthesis by
      double-stranded RNA-activated protein kinase.
AB  - In human cells infected with herpes simplex virus 1 the double-stranded RNA
      dependent protein kinase (PKR) is activated but phosphorylation of the alpha
      subunit of eukaryotic translation initiation factor 2 (eIF-2) and total shutoff
      of protein synthesis is observed only in cells infected with gamma(1)z34.5-
      mutants. The carboxyl-terminal 64 aa of gamma(1)34.5 protein are homologous to
      the corresponding domain of MyD116, the murine growth arrest and DNA damage gene
      34 (GADD34) protein and the two domains are functionally interchangeable in
      infected cells. This report shows that (i) the carboxyl terminus of MyD116
      interacts with protein phosphatase 1alpha in yeast, and both MyD116 and
      gamma(1)34.5 interact with protein phosphatase 1alpha in vitro; (ii) protein
      synthesis in infected cells is strongly inhibited by okadaic acid, a phosphatase
      1 inhibitor; and (iii) the alpha subunit in purified eIF-2 phosphorylated in
      vitro is specifically dephosphorylated by S10 fractions of wild-type infected
      cells at a rate 3000 times that of mock-infected cells, whereas the eIF-2alpha-P
      phosphatase activity of gamma(1)34.5- virus infected cells is lower than that of
      mock-infected cells. The eIF-2alpha-P phosphatase activities are sensitive to
      inhibitor 2. In contrast to eIF-2alpha-P phosphatase activity, extracts of mock
      infected cells exhibit a 2-fold higher phosphatase activity on [32P]phosphorylase
      than extracts of infected cells. These results indicate that in infected cells,
      gamma(1)34.5 interacts with and redirects phosphatase to dephosphorylate eIF
      2alpha to enable continued protein synthesis despite the presence of activated
      PKR. The GADD34 protein may have a similar function in eukaryotic cells. The
      proposed mechanism for maintenance of protein synthesis in the face of double
      stranded RNA accumulation is different from that described for viruses examined
      to date.

PMID- 9023345
TI  - Demonstration of mechanical connections between integrins, cytoskeletal
      filaments, and nucleoplasm that stabilize nuclear structure.
AB  - We report here that living cells and nuclei are hard-wired such that a mechanical
      tug on cell surface receptors can immediately change the organization of
      molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by
      micromanipulating bound microbeads or micropipettes, cytoskeletal filaments
      reoriented, nuclei distorted, and nucleoli redistributed along the axis of the
      applied tension field. These effects were specific for integrins, independent of
      cortical membrane distortion, and were mediated by direct linkages between the
      cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the
      nucleus at low strain; however, tearing of the actin gel resulted with greater
      distortion. In contrast, intermediate filaments effectively mediated force
      transfer to the nucleus under both conditions. These filament systems also acted
      as molecular guy wires to mechanically stiffen the nucleus and anchor it in
      place, whereas microtubules acted to hold open the intermediate filament lattice
      and to stabilize the nucleus against lateral compression. Molecular connections
      between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore
      provide a discrete path for mechanical signal transfer through cells as well as a
      mechanism for producing integrated changes in cell and nuclear structure in
      response to changes in extracellular matrix adhesivity or mechanics.

PMID- 9023346
TI  - Activation of the cell death program by inhibition of proteasome function.
AB  - Activation of proteolytic enzymes, including cysteine proteases of the ced-3/ICE
      family, is a characteristic feature of the apoptotic program. In contrast, the
      role of the proteasome as the major nonlysosomal machinery to degrade or process
      proteins by ATP/ubiquitin-dependent proteolysis in this process is less clear. In
      human leukemic HL60 cells, inhibition of proteasome-mediated proteolysis by
      specific proteasomal inhibitors leads to the rapid induction of apoptosis as
      judged by morphological changes as well as by nuclear condensation and DNA
      fragmentation. HL60 apoptosis is due to activation of CPP32, a member of the ced
      3/ICE family of cysteine proteases, and appears to occur independently from ICE
      activity. HL60 apoptosis is accompanied by an increase in the concentration of
      the cyclin-dependent kinase inhibitor p27Kip1. Labeling of the cells by the TUNEL
      technique demonstrates that HL60 cells undergoing apoptosis are primarily in the
      G1 phase of the cell cycle. Proteasomal activity therefore appears to be required
      in proliferating, but not in quiescent, HL60 cells for cell survival as well as
      normal progression through the cell cycle.

PMID- 9023348
TI  - DNA double-strand-break sensitivity, DNA replication, and cell cycle arrest
      phenotypes of Ku-deficient Saccharomyces cerevisiae.
AB  - In mammalian cells, the Ku heterodimer is involved in DNA double-strand-break
      recognition and repair. We have established in yeast a connection between Ku
      activity and DNA double-strand-break damage repair, and a connection between Ku
      activity and commitment to DNA replication. We generated double-stranded DNA
      breaks in yeast cells in vivo by expressing a restriction endonuclease and have
      shown that yeast mutants lacking Ku p70 activity died while isogenic wild-type
      cells did not. Moreover, we have discovered that DNA damage occurs spontaneously
      during normal yeast mitotic growth, and that Ku functions in repair of this
      damage. We also observed that mitotically growing Ku p70 mutants have an
      anomalously high DNA content, suggesting a role for Ku in regulation of DNA
      synthesis. Finally, we present evidence that Ku p70 function is conserved between
      yeast, Drosophila, and humans.

PMID- 9023347
TI  - Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways.
AB  - The switch from a quiescent tumor to an invasive tumor is accompanied by the
      acquisition of angiogenic properties. This phenotypic change likely requires a
      change in the balance of angiogenic stimulators and angiogenic inhibitors. The
      nature of the angiogenic switch is not known. Here, we show that introduction of
      activated H-ras into immortalized endothelial cells is capable of activating the
      angiogenic switch. Angiogenic switching is accompanied by up-regulation of
      vascular endothelial growth factor and matrix metalloproteinase (MMP) bioactivity
      and downregulation of tissue inhibitor of MMP. Furthermore, we show that
      inhibition of phosphatidylinositol-3-kinase leads to partial inhibition of tumor
      angiogenesis, thus demonstrating that activated H-ras activates tumor
      angiogenesis through two distinct pathways. Finally, we show evidence for two
      forms of tumor dormancy.

PMID- 9023349
TI  - Nef proteins encoded by human and simian immunodeficiency viruses induce the
      accumulation of endosomes and lysosomes in human T cells.
AB  - The nef gene of human and simian immunodeficiency viruses encodes a 27-32-kDa
      myristoylated protein that is expressed at high levels early after infection.
      Many functions have been ascribed to the Nef protein, including the down
      regulation of cell surface CD4 and a role in viral infectivity. This report
      describes a novel effect of the Nef protein on human T cells. Electron microscopy
      was used to examine human T cell lines stably expressing functionally active
      simian or human immunodeficiency virus type 1 Nef proteins. These studies
      revealed that the subcellular morphology of Nef-expressing cells was dramatically
      altered as compared with control cells. The Nef-expressing cells contained
      numerous membrane-bound vesicles prominently displayed throughout the cytoplasm.
      The vesicles were analyzed by immunoelectron microscopy (IEM) and by the
      accumulation of internalized nonspecific membrane tracer, and thus identified as
      late endosomes and lysosomes. The accumulation of endosomes and lysosomes in
      response to the expression of Nef was a consistent finding, observed with several
      different viral isolates and human T cell lines.

PMID- 9023350
TI  - Cell-cell contact changes the dynamics of lamellar activity in nontransformed
      epitheliocytes but not in their ras-transformed descendants.
AB  - We investigated the structural and functional alterations of active lamellae
      during initial cell-cell collision and establishment of cell-cell contacts in
      wounded cultures of nontransformed rat epitheliocytes (IAR-2 line) and their ras
      transformed descendants (C4 line). Typically, the leading edges of nontransformed
      cells formed multiple transient contacts followed by establishment of small,
      stable contacts that would undergo lateral expansion. Formation and expansion of
      the contact area was accompanied by accumulation of the cell-cell adhesion
      molecules E-cadherin, beta-catenin, and plakoglobin. During lateral expansion,
      the circumferential bundles of actin filaments, characteristic of IAR-2 cells,
      disassembled at the site of stable contact forming a concave arc-like actin
      bundle between adjacent cells at the expanding edge. Pseudopodial activity was
      completely inhibited in the contact zone and partially inhibited at the free
      lamellar edges adjacent to the zone of contact. Con A-coated beads on the plasma
      membrane at the zone of contact stopped undergoing centripetal transport but now
      moved along the cell-cell boundary. On the other hand, ras-transformed cells
      developed overlapping lamellae and exhibited no detectable change in activity of
      lamellae, localization of adhesion molecules, and organization of the actin
      cytoskeleton. We propose that contact-induced reorganization of cell surface
      adhesion molecules and the underlying cortical cytoskeleton leads to development
      of lateral traction that may be an essential element in inducing expansion of the
      contact and in inhibiting local pseudopodial activity.

PMID- 9023351
TI  - Targeted disruption of the mouse alpha A-crystallin gene induces cataract and
      cytoplasmic inclusion bodies containing the small heat shock protein alpha B
      crystallin.
AB  - alpha A-crystallin (alpha A) and alpha B-crystallin (alpha B) are among the
      predominant proteins of the vertebrate eye lens. In vitro, the alpha-crystallins,
      which are isolated together as a high molecular mass aggregate, exhibit a number
      of properties, the most interesting of which is their ability to function as
      molecular chaperones for other proteins. Here we begin to examine the in vivo
      functions of alpha-crystallin by generating mice with a targeted disruption of
      the alpha A gene. Mice that are homozygous for the disrupted allele produce no
      detectable alpha A in their lenses, based on protein gel electrophoresis and
      immunoblot analysis. Initially, the alpha A-deficient lenses appear structurally
      normal, but they are smaller than the lenses of wild-type littermates. alpha A-/-
      lenses develop an opacification that starts in the nucleus and progresses to a
      general opacification with age. Light and transmission electron microscopy reveal
      the presence of dense inclusion bodies in the central lens fiber cells. The
      inclusions react strongly with antibodies to alpha B but not significantly with
      antibodies to beta- or gamma-crystallins. In addition, immunoblot analyses
      demonstrate that a significant portion of the alpha B in alpha A-/- lenses shifts
      into the insoluble fraction. These studies suggest that alpha A is essential for
      maintaining lens transparency, possibly by ensuring that alpha B or proteins
      closely associated with this small heat shock protein remain soluble.

PMID- 9023352
TI  - Inherited somatic mosaicism caused by an intracisternal A particle insertion in
      the mouse tyrosinase gene.
AB  - A recessive, fully penetrant mutation (c(m1OR)) at the mouse albino locus that
      results in coat-color mottling has been characterized at the molecular level.
      Restriction mapping and DNA sequencing analyses provide evidence that mutants
      carry a 5.4-kb intracisternal A particle (IAP) element insertion upstream of the
      tyrosinase (Tyr) promoter. Northern blot analysis and reverse transcription-PCR
      results show that the tyrosinase gene is expressed at much lower levels in mutant
      than in wild-type mice. The mutant Tyr gene still retains the tissue-specific
      expression pattern, and the Tyr transcript is not initiated from the IAP long
      terminal repeat promoter. We propose that the IAP insertion isolates the promoter
      of the tyrosinase gene from upstream cis-acting regulatory elements, leading to a
      substantially decreased level of Tyr gene expression in mutants.

PMID- 9023354
TI  - An alpha-E-catenin gene trap mutation defines its function in preimplantation
      development.
AB  - Catenins are proteins associated with the cytoplasmic domain of cadherins, a
      family of transmembrane cell adhesion molecules. The cadherin-catenin adhesion
      system is involved in morphogenesis during development and in the maintenance of
      the integrity of different tissue types. Using a gene trap strategy, we have
      isolated a mouse mutation for the gene encoding the alpha-E-catenin. This form of
      the alpha-catenin appears frequently coexpressed with E-cadherin in epithelial
      cell types. The mutation obtained eliminates the carboxyl-terminal third of the
      protein but nevertheless provokes a complete loss-of-function phenotype.
      Homozygous mutants show disruption of the trophoblast epithelium (the first
      differentiated embryonic tissue), and development is consequently blocked at the
      blastocyst stage. This phenotype parallels the defects observed in E-cadherin
      mutant embryos. Our results show the requirement of the alpha-E-catenin carboxy
      terminus for its function and represent evidence of the role of the alpha-E
      catenin in vivo, identifying this molecule as the natural partner of the E
      cadherin in trophoblast epithelium.

PMID- 9023353
TI  - Role of the Xlim-1 and Xbra genes in anteroposterior patterning of neural tissue
      by the head and trunk organizer.
AB  - Anteroposterior patterning of neural tissue is thought to be directed by the
      axial mesoderm which is functionally divided into head and trunk organizer. The
      LIM class homeobox gene Xlim-1 is expressed in the entire axial mesoderm, whereas
      the distinct transcription factor Xbra is expressed in the notochord but not in
      the prechordal mesoderm. mRNA injection experiments showed that Xenopus animal
      explants (caps) expressing an activated form of Xlim-1 (a LIM domain mutant named
      3m) induce anterior neural markers whereas caps coexpressing Xlim-1/3m and Xbra
      induce posterior neural markers. These data indicate that, in terms of neural
      inducing ability, Xlim-1/3m-expressing caps correspond to the head organizer and
      Xlim-1/3m plus Xbra-coexpressing caps to the trunk organizer. Thus the expression
      domains of Xlim-1 and Xbra correlate with, and possibly define, the functional
      domains of the organizer. In animal caps Xlim-1/3m initiates expression of a
      neuralizing factor, chordin, whereas Xbra activates embryonic fibroblast growth
      factor (eFGF) expression, as reported previously; these factors could mediate the
      neural inducing and patterning effects that were observed. A dominant-negative
      FGF receptor (XFD) inhibits posteriorization by Xbra in a dose-dependent manner,
      supporting the suggestion that eFGF or a related factor has posteriorizing
      influence.

PMID- 9023355
TI  - The analysis of ontogenetic trajectories: when a change in size or shape is not
      heterochrony.
AB  - Heterochrony has become a central organizing concept relating development and
      evolution. Unfortunately, the standard definition of heterochrony--evolutionary
      change in the rate or timing of developmental processes--is so broad as to apply
      to any case of phenotypic evolution. Conversely, the standard classes of
      heterochrony only accurately describe a small subset of the possible ways that
      ontogeny can change. I demonstrate here that the nomenclature of heterochrony is
      meaningful only when there is a uniform change in the rate or timing of some
      ontogenetic process, with no change in the internal structure of that process.
      Given two ontogenetic trajectories, we can test for this restricted definition of
      heterochrony by asking if a uniform stretching or translation of one trajectory
      along the time axis superimposes it on the other trajectory. If so, then the
      trajectories are related by a uniform change in the rate or timing of
      development. If not, then there has been change within the ontogenetic process
      under study. I apply this technique to published data on fossil Echinoids and to
      the comparison of human and chimpanzee growth curves. For the Echinoids, some
      characters do show heterochrony (hypermorphosis), while others, which had
      previously been seen as examples of heterochrony, fail the test--implying that
      their evolution involved changes in the process of development, not just the rate
      at which it proceeded. Analysis of human and chimpanzee growth curves indicates a
      combination of neoteny and sequential hypermorphosis, two processes previously
      seen as alternate explanations for the differences between these species.

PMID- 9023356
TI  - dissatisfaction, a gene involved in sex-specific behavior and neural development
      of Drosophila melanogaster.
AB  - Few mutations link well defined behaviors with individual neurons and the
      activity of specific genes. In Drosophila, recent evidence indicates the presence
      of a doublesex-independent pathway controlling sexual behavior and neuronal
      differentiation. We have identified a gene, dissatisfaction (dsf), that affects
      sex-specific courtship behaviors and neural differentiation in both sexes without
      an associated general behavioral debilitation. Male and female mutant animals
      exhibit abnormalities in courtship behaviors, suggesting a requirement for dsf in
      the brain. Virgin dsf females resist males during courtship and copulation and
      fail to lay mature eggs. dsf males actively court and attempt copulation with
      both mature males and females but are slow to copulate because of maladroit
      abdominal curling. Structural abnormalities in specific neurons indicate a role
      for dsf in the differentiation of sex-specific abdominal neurons. The egg-laying
      defect in females correlates with the absence of motor neuronal innervation on
      uterine muscles, and the reduced abdominal curling in males correlates with
      alteration in motor neuronal innervation of male ventral abdominal muscles.
      Epistasis experiments show that dsf acts in a tra-dependent and dsx-independent
      manner, placing dsf in the dsx-independent portion of the sex determination
      cascade.

PMID- 9023357
TI  - Combined effects of insulin treatment and adipose tissue-specific agouti
      expression on the development of obesity.
AB  - The agouti gene product is a secreted protein that acts in a paracrine manner to
      regulate coat color in mammals. Several dominant mutations at the agouti locus in
      mice cause the ectopic, ubiquitous expression of agouti, resulting in a condition
      similar to adult-onset obesity and non-insulin-dependent diabetes mellitus. The
      human agouti protein is 85% homologous to mouse agouti; however, unlike the mouse
      agouti gene, human agouti is normally expressed in adipose tissue. To address
      whether expression of agouti in human adipose tissue is physiologically relevant,
      transgenic mice were generated that express agouti in adipose tissue. Similar to
      most humans, these mice do not become obese or diabetic. However, we found that
      daily insulin injections significantly increased weight gain in the transgenic
      lines expressing agouti in adipose tissue, but not in nontransgenic mice. These
      results suggest that insulin triggers the onset of obesity and that agouti
      expression in adipose tissue potentiates this effect. Accordingly, the
      investigation of agouti's role in obesity and non-insulin-dependent diabetes
      mellitus in mice holds significant promise for understanding the pathophysiology
      of human obesity.

PMID- 9023358
TI  - Normal cerebellar development but susceptibility to seizures in mice lacking G
      protein-coupled, inwardly rectifying K+ channel GIRK2.
AB  - G protein-gated, inwardly rectifying K+ channels (GIRK) are effectors of G
      protein-coupled receptors for neurotransmitters and hormones and may play an
      important role in the regulation of neuronal excitability. GIRK channels may be
      important in neurodevelopment, as suggested by the recent finding that a point
      mutation in the pore region of GIRK2 (G156S) is responsible for the weaver (wv)
      phenotype. The GIRK2 G156S gene gives rise to channels that exhibit a loss of K+
      selectivity and may also exert dominant-negative effects on G(betagamma)
      activated K+ currents. To investigate the physiological role of GIRK2, we
      generated mutant mice lacking GIRK2. Unlike wv/wv mutant mice, GIRK2 -/- mice are
      morphologically indistinguishable from wild-type mice, suggesting that the wv
      phenotype is likely due to abnormal GIRK2 function. Like wv/wv mice, GIRK2 -/-
      mice have much reduced GIRK1 expression in the brain. They also develop
      spontaneous seizures and are more susceptible to pharmacologically induced
      seizures using a gamma-aminobutyric acid antagonist. Moreover, wv/- mice exhibit
      much milder cerebellar abnormalities than wv/wv mice, indicating a dosage effect
      of the GIRK2 G156S mutation. Our results indicate that the weaver phenotypes
      arise from a gain-of-function mutation of GIRK2 and that GIRK1 and GIRK2 are
      important mediators of neuronal excitability in vivo.

PMID- 9023359
TI  - Site-directed mutations reveal long-range compensatory interactions in the Adh
      gene of Drosophila melanogaster.
AB  - Long-range interactions between the 5' and 3' ends of mRNA molecules have been
      suggested to play a role in the initiation of translation and the regulation of
      gene expression. To identify such interactions and to study their molecular
      evolution, we used phylogenetic analysis to generate a model of mRNA higher-order
      structure in the Adh transcript of Drosophila melanogaster. This model predicts
      long-range, tertiary contacts between a region of the protein-encoding sequence
      just downstream of the start codon and a conserved sequence in the 3'
      untranslated region (UTR). To further examine the proposed structure, site
      directed mutations were generated in vitro in a cloned D. melanogaster Adh gene,
      and the mutant constructs were introduced into the Drosophila germ line through P
      element mediated transformation. Transformants were spectrophotometrically
      assayed for alcohol dehydrogenase activity. Our results indicate that
      transformants containing a silent mutation near the start of the protein-encoding
      sequence show an approximately 15% reduction in alcohol dehydrogenase activity
      relative to wild-type transformants. This activity can be restored to wild-type
      levels by a second, compensatory mutation in the 3' UTR. These observations are
      consistent with a higher-order structure model that includes long-range
      interactions between the 5' and 3' ends of the Adh mRNA. However, our results do
      not fit the classical compensatory substitution model because the second mutation
      by itself (in the 3' UTR) did not show a measurable reduction in gene expression.

PMID- 9023360
TI  - Bacterial infection as assessed by in vivo gene expression.
AB  - In vivo expression technology (IVET) has been used to identify > 100 Salmonella
      typhimurium genes that are specifically expressed during infection of BALB/c mice
      and/or murine cultured macrophages. Induction of these genes is shown to be
      required for survival in the animal under conditions of the IVET selection. One
      class of in vivo induced (ivi) genes, iviVI-A and iviVI-B, constitute an operon
      that resides in a region of the Salmonella genome with low G+C content and
      presumably has been acquired by horizontal transfer. These ivi genes encode
      predicted proteins that are similar to adhesins and invasins from prokaryotic and
      eukaryotic pathogens (Escherichia coli [tia], Plasmodium falciparum [PfEMP1]) and
      have coopted the PhoPQ regulatory circuitry of Salmonella virulence genes.
      Examination of the in vivo induction profile indicates (i) many ivi genes encode
      regulatory functions (e.g., phoPQ and pmrAB) that serve to enhance the
      sensitivity and amplitude of virulence gene expression (e.g., spvB); (ii) the
      biochemical function of many metabolic genes may not represent their sole
      contribution to virulence; (iii) the host ecology can be inferred from the
      biochemical functions of ivi genes; and (iv) nutrient limitation plays a dual
      signaling role in pathogenesis: to induce metabolic functions that complement
      host nutritional deficiencies and to induce virulence functions required for
      immediate survival and spread to subsequent host sites.

PMID- 9023361
TI  - 5-Methylcytosine is not a mutation hot spot in nondividing Escherichia coli.
AB  - Spontaneous deamination of 5-methylcytosine (5meC) causes hot spots of CxG -->
      TxA mutations in Escherichia coli and in human cells. In E. coli, the resulting
      TxG mispairs can be corrected to CxG by very short patch (VSP) repair, which
      requires the product of gene vsr. Mutation hot spots in genes of replicating vsr+
      bacteria are attributable to low Vsr activity. To determine the rate of
      deamination of 5meC and the efficiency of VSP repair in nondividing bacteria, we
      used kanamycin-sensitive (KanS) lysogens containing a lambda kan- prophage.
      Deamination of a 5meC in the kan- gene resulted in mutation to kanamycin
      resistance (KanR). Lysogens containing a single lambda kan- prophage per
      bacterial genome were grown in synthetic medium with limiting amino acids and
      stored at 15 degrees C or 37 degrees C. In the absence of VSP repair, KanR
      mutants accumulated at the rate of approximately 1.3 x 10(-7) per bacterium per
      day at 37 degrees C. This is similar to the 5meC --> T mutation rate reported for
      DNA in solution. In vsr+ bacteria, the KanR accumulation rate was 3 x 10(-9) per
      bacterium per day, which is not significantly higher than the rate observed when
      the target cytosine was unmethylated. The increase in KanR mutants was barely
      detectable in vsr+ cultures stored at 15 degrees C for 4 months. It is likely
      that mutation hot spots at 5meC in rapidly dividing cells are attributable to
      insufficient time for TxG correction in the interval between deamination of 5meC
      and subsequent DNA replication. DNA synthesis occurred in bacteria starved for
      amino acids and this synthesis was not highly mutagenic.

PMID- 9023362
TI  - Escherichia coli DNA polymerase II catalyzes chromosomal and episomal DNA
      synthesis in vivo.
AB  - We have investigated a role for Escherichia coli DNA polymerase II (Pol II) in
      copying chromosomal and episomal DNA in dividing cells in vivo. Forward mutation
      frequencies and rates were measured at two chromosomal loci, rpoB and gyrA, and
      base substitution and frameshift mutation frequencies were measured on an
      F'(lacZ) episome. To amplify any differences in polymerase error rates, methyl
      directed mismatch repair was inactivated. When wild-type Pol II (polB+) was
      replaced on the chromosome by a proofreading-defective Pol II exo- (polBex1),
      there was a significant increase in mutation frequencies to rifampicin resistance
      (RifR) (rpoB) and nalidixic acid resistance (NalR) (gyrA). This increased
      mutagenesis occurred in the presence of an antimutator allele of E. coli DNA
      polymerase III (Pol III) (dnaE915), but not in the presence of wild-type Pol III
      (dnaE+), suggesting that Pol II can compete effectively with DnaE915 but not with
      DnaE+. Sequencing the RifR mutants revealed a G --> A hot spot highly specific to
      Pol II exo-. Pol II exo- caused a significant increase in the frequency of base
      substitution and frameshift mutations on F' episomes, even in dnaE+ cells,
      suggesting that Pol II is able to compete with Pol III for DNA synthesis on F
      episomes.

PMID- 9023363
TI  - Expression genetics in cancer: shifting the focus from DNA to RNA.
AB  - Expression genetics is a conceptually different approach to the identification of
      cancer-related genes than the search for mutations at the genome level. While
      mutations lie at the heart of cancer, at least in its early stages, what is
      recognized here are phenotypic changes usually many steps removed from the
      initiating mutation. Classically cancer geneticists have concentrated on genomic
      changes and have ignored the productive potential of examining downstream events
      based on screening for differential gene expression between tumor cells and well
      matched normal counterparts. Genes involved in cancer affect the normal functions
      of many cellular processes: not only proliferation but cell-cell and cell-matrix
      interactions, DNA repair, invasion and motility, angiogenesis, senescence,
      apoptosis, and others. Yet very few cancer-related genes affecting these
      processes have been identified in human cancers by classical methods to find
      mutated genes despite enormous efforts. I report here our success in readily
      isolating more than 100 candidate tumor suppressor genes from human tissue,
      estimated to represent roughly 20% of the total genes recoverable by this
      approach. Half of the genes are unknown and the other half include
      representatives of most known cancer processes. Because their expression is lost
      during cancer progression, they may be useful tumor markers for diagnosis and
      prognosis. Because these genes are not mutated, they provide opportunities for
      pharmacological intervention by inducing their reexpression.

PMID- 9023364
TI  - Reduction in receptors for bombesin and epidermal growth factor in xenografts of
      human small-cell lung cancer after treatment with bombesin antagonist RC-3095.
AB  - Antagonists of bombesin/gastrin-releasing peptide (BN/GRP) have been developed to
      inhibit the stimulatory effects of BN/GRP on the mitogenesis of tumor cells such
      as human small-cell lung carcinoma (SCLC). The mode of action of these
      antagonists is not completely understood. In this study, we evaluated the effect
      of BN/GRP antagonist RC-3095 on receptors for BN/GRP and epidermal growth factor
      (EGF) in H-128 human SCLC line xenografted into nude mice. Treatment with RC
      3095, administered s.c. at a dose of 20 microg/day per animal for 4 weeks caused
      a 70% reduction in tumor volume and weight. Membrane receptors for BN/GRP and EGF
      were characterized in untreated and treated animals. In the control group, [125I
      Tyr4]BN was bound to a single class of specific, high affinity binding sites with
      a dissociation constant (Kd) = 6.55 +/- 0.93 nM and maximal binding capacity
      (Bmax) = 512.8 +/- 34.8 fmol/mg membrane protein. Therapy with RC-3095 decreased
      the concentration of BN/GRP receptors on H-128 SCLC tumor membranes. Specific,
      high affinity binding sites for EGF with Kd = 1.78 +/- 0.26 nM and Bmax = 216.8
      +/- 19.6 fmol/mg membrane protein were also found on the untreated H-128 SCLC
      tumors. Treatment with RC-3095 significantly decreased Bmax of receptors for EGF.
      Our results indicate that the suppression of growth of H-128 SCLC by BN
      antagonist RC-3095 is accompanied by a decrease in the number of receptors for
      both BN/GRP and EGF. These observations are in agreement with the results
      obtained in other experimental cancers. The findings on antagonist RC-3095
      reinforce the view that both BN/GRP and EGF receptors participate in a cascade of
      events involved in the growth of SCLC and other cancers. Although the complete
      mechanisms of action of antagonist RC-3095 remain to be elucidated, the antitumor
      effect could be the result of the fall in the EGF receptor number, which might
      lead to a decrease in EGF receptor autophosphorylation.

PMID- 9023365
TI  - Foreign (M13) DNA ingested by mice reaches peripheral leukocytes, spleen, and
      liver via the intestinal wall mucosa and can be covalently linked to mouse DNA.
AB  - Food-ingested foreign DNA is not completely degraded in the gastrointestinal
      tract of mice. Phage M13mp18 DNA as a test molecule devoid of homology to mouse
      DNA was pipette-fed to or added to the food supply of mice. The fate of this
      foreign DNA in the animals was followed by several methods. In 84 animals,
      fragments of M13mp18 DNA were detected in the contents of the small intestine,
      the cecum (until 18 h), the large intestine, or the feces. In 254 animals,
      M13mp18 DNA fragments of up to 976 bp were found in blood 2-8 h after feeding. In
      buffer-fed control animals, M13mp18 DNA could not be detected. M13mp18 DNA
      fragments were traced by PCR in peripheral leukocytes and located by fluorescent
      in situ hybridization in about 1 of 1000 white cells between 2 and 8 h, and in
      spleen or liver cells up to 24 h after feeding, but not later. M13mp18 DNA could
      be traced by fluorescent in situ hybridization in the columnar epithelial cells,
      in the leukocytes in Peyer's patches of the cecum wall, in liver cells, and in B
      cells, T cells, and macrophages from spleen. These findings suggest transport of
      foreign DNA through the intestinal wall and Peyer's patches to peripheral blood
      leukocytes and into several organs. Upon extended feeding, M13mp18 DNA could be
      recloned from total spleen DNA into a lambda vector. Among about 2.5 x 10(7)
      lambda plaques, one plaque was isolated that contained a 1299 nucleotide pair
      fragment (nt 4736-6034) of sequence-identified M13mp18 DNA. This fragment was
      covalently linked to an 80 nt DNA segment with 70% homology to the mouse IgE
      receptor gene. The DNA from another lambda plaque also contained mouse DNA,
      bacterial DNA, and rearranged lambda DNA. Two additional plaques contained
      M13mp18 DNA fragments of at least 641 (nt 2660-3300) or 794 (nt 4640-5433)
      nucleotide pairs. The medical and evolutionary implications of these observations
      may be considerable.

PMID- 9023366
TI  - Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide
      in the pathogenesis of cystic fibrosis lung disease.
AB  - An unresolved question in cystic fibrosis (CF) research is how mutations of the
      CF transmembrane conductance regulator, a Cl ion channel, cause airway mucus
      obstruction leading to fatal lung disease. Recent evidence has linked the CF
      transmembrane conductance regulator mutation to the onset and persistence of
      Pseudomonas aeruginosa infection in the airways, and here we provide evidence
      directly linking P. aeruginosa infection to mucus overproduction. We show that P.
      aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin
      gene MUC 2 in epithelial cells via inducible enhancer elements and that this
      effect is blocked by the tyrosine kinase inhibitors genistein and tyr-phostin AG
      126. These findings improve our understanding of CF pathogenesis and suggest that
      the attenuation of mucin production by lipopolysaccharide antagonists and
      tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.

PMID- 9023367
TI  - HIV Rev-dependent binding of SF2/ASF to the Rev response element: possible role
      in Rev-mediated inhibition of HIV RNA splicing.
AB  - Production of the structural and enzymatic proteins of type 1 human
      immunodeficiency virus (HIV-1) is controlled by the rev regulatory gene product.
      The 116-amino acid Rev protein acts by binding to the Rev response element (RRE),
      a complex RNA stem-loop structure located within the env gene of HIV. Rev exerts
      a series of posttranscriptional effects, including the inhibition of viral RNA
      splicing, the activation of nuclear export of incompletely spliced viral RNAs,
      and the enhancement of translation of RRE-containing RNAs. Our studies now
      demonstrate that at least one member of the SR family of splicing factors,
      SF2/ASF, specifically binds to a subregion of the RRE in vitro in a Rev-dependent
      manner. Furthermore, expression of high levels of SF2/ASF inhibits Rev function
      and impairs HIV replication in vivo. Both the in vitro binding of SF2/ASF to the
      Rev/RRE complex and the in vivo inhibition of Rev action by SF2/ASF are abrogated
      by mutation of the N-terminal RNA recognition motif but are not affected by
      mutation of the C-terminal arginine-serine-rich domain. These findings suggest
      that Rev inhibition of HIV splicing likely involves recruitment of the essential
      splicing factor SF2/ASF to the Rev/RRE complex. However, these inhibitory effects
      of Rev on viral RNA splicing are apparently overcome by augmenting the
      intracellular levels of SF2/ASF expression.

PMID- 9023368
TI  - Vascular endothelial growth factor/vascular permeability factor is an autocrine
      growth factor for AIDS-Kaposi sarcoma.
AB  - Kaposi sarcoma (KS) is the most common tumor associated with HIV-1 infection and
      develops in nearly 30% of cases. The principal features of this tumor are
      abnormal vascularization and the proliferation of endothelial cells and spindle
      (tumor) cells. KS-derived spindle cells induce vascular lesions and display
      enhanced vascular permeability when inoculated subcutaneously in the nude mouse.
      This finding suggests that angiogenesis and capillary permeability play a central
      role in the development and progression of KS. In this study, we show that AIDS
      KS cell lines express higher levels of vascular endothelial growth
      factor/vascular permeability factor (VEGF/VGF) than either human umbilical vein
      endothelial cells or human aortic smooth muscle cells. AIDS-KS cells and primary
      tumor tissues also expressed high levels of Flt-1 and KDR, the receptors for
      VEGF, while the normal skin of the same patients did not show any expression. We
      further demonstrate that VEGF antisense oligonucleotides AS-1 and AS-3
      specifically block VEGF mRNA and protein production and inhibit KS cell growth in
      a dose-dependent manner. Furthermore, growth of KS cells in nude mice was
      specifically inhibited by VEGF antisense oligonucleotides. These results show
      that VEGF is an autocrine growth factor for AIDS-KS cells. To our knowledge, this
      is the first report that shows that VEGF acts as a growth stimulator in a human
      tumor. Inhibitors of VEGF or its cognate receptors may thus be candidates for
      therapeutic intervention.

PMID- 9023369
TI  - Nested DNA inversion as a paradigm of programmed gene rearrangement.
AB  - Programmed gene rearrangements are employed by a variety of microorganisms,
      including viruses, prokaryotes, and simple eukaryotes, to control gene
      expression. In most instances in which organisms mediate host evasion by large
      families of homologous gene cassettes, the mechanism of variation is not thought
      to involve DNA inversion. Here we report that Campylobacter fetus, a pathogenic
      Gram-negative bacterium, reassorts a single promoter, controlling surface-layer
      protein expression, and one or more complete ORFs strictly by DNA inversion.
      Rearrangements were independent of the distance between sites of inversion. These
      rearrangements permit variation in protein expression from the large surface
      layer protein gene family and suggest an expanding paradigm of programmed DNA
      rearrangements among microorganisms.

PMID- 9023370
TI  - An infectious arterivirus cDNA clone: identification of a replicase point
      mutation that abolishes discontinuous mRNA transcription.
AB  - Equine arteritis virus (EAV) is a positive-strand RNA virus that uses a
      discontinuous transcription mechanism to generate a nested set of six subgenomic
      mRNAs from which its structural genes are expressed. A stable bacterial plasmid
      (pEAV030) containing a full-length cDNA copy of the 12.7-kb EAV genome was
      constructed. After removal of a single point mutation in the replicase gene, RNA
      transcripts generated in vitro from pEAV030 were shown to be infectious upon
      electroporation into BHK-21 cells. A genetic marker mutation was introduced at
      the cDNA level and recovered from the genome of the progeny virus. The potential
      of pEAV030 as a tool to express foreign genes was demonstrated by the efficient
      expression of the chloramphenicol acetyltransferase (CAT) reporter gene from two
      different subgenomic mRNAs. The point mutation that initially rendered the full
      length clone noninfectious was found to result in a particularly intriguing
      phenotype: RNA carrying this mutation can replicate efficiently but does not
      produce the subgenomic mRNAs required for structural protein expression. To our
      knowledge, this mutant provides the first evidence that the requirements for
      arterivirus genome replication and discontinuous mRNA synthesis are, at least
      partially, different and that these processes may be separated experimentally.

PMID- 9023371
TI  - Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t
      SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses.
AB  - Neurotransmitter release requires the specific docking of synaptic vesicles to
      the presynaptic plasma membrane followed by a calcium-triggered fusion event.
      Herein we report a previously unsuspected interaction of the synaptic vesicle
      protein and likely calcium sensor synaptotagmin with the plasma membrane t-SNARE
      SNAP-25. This interaction appears to resolve the apparent paradox that synaptic
      vesicles are capable of docking even when VAMP (vesicle-associated membrane
      protein) or syntaxin is cleaved or deleted and suggests that two species of v
      SNAREs (VAMP and synaptotagmin) and two species of t-SNAREs (SNAP-25 and
      syntaxin) interact to functionally dock synaptic vesicles.

PMID- 9023373
TI  - GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines,
      and somata in the CA1 region of the hippocampus.
AB  - Electron microscopic analysis of the CA1 region of the rat hippocampus revealed
      that specific immunoreactivity (IR) for a G protein-gated, inwardly rectifying
      potassium channel (GIRK1) was present exclusively in neurons and predominantly
      located in spiny dendrites of pyramidal cells. Within stratum lacunosum
      moleculare and the superficial stratum radiatum, GIRK1-IR was often present
      immediately adjacent to asymmetric (excitatory-type) postsynaptic densities in
      dendritic spines. The subcellular localization of GIRK1-IR in the Golgi apparatus
      of pyramidal cell somata and in the plasma membrane of dendrites and dendritic
      spines confirms the hypothesis that GIRK1 is synthesized by pyramidal cells and
      transported to the more distal dendritic processes. G protein-coupled receptor
      activation of a dendritic potassium conductance would attenuate the propagation
      of excitatory synaptic inputs and thereby produce postsynaptic inhibition. Thus,
      these results show that the GIRK family of channels joins the list of voltage
      sensitive channels now known to be expressed in dendritic spines.

PMID- 9023372
TI  - Activation of calcium-dependent potassium channels in mouse [correction of rat]
      brain neurons by neurotrophin-3 and nerve growth factor.
AB  - The neurotrophins are signaling factors that are essential for survival and
      differentiation of distinct neuronal populations during the development and
      regeneration of the nervous system. The long-term effects of neurotrophins have
      been studied in detail, but little is known about their acute effects on neuronal
      activity. Here we use permeabilized whole-cell patch clamp to demonstrate that
      neurotrophin-3 (NT-3) and nerve growth factor activate calcium-dependent,
      paxilline-sensitive potassium channels (BK channels) in cortical neurons.
      Application of NT-3 or nerve growth factor produced a rapid and gradual rise in
      BK current that was sustained for 30-50 min; brain-derived neurotrophic factor,
      ciliary neurotrophic factor, and insulin-like growth factor-1 had no significant
      effect. The response to NT-3 was blocked by inhibitors of protein kinases,
      phospholipase C, and serine/threonine protein phosphatase 1 and 2a. Omission of
      Ca2+ from the extracellular medium prevented the NT-3 effect. Our results
      indicate that NT-3 stimulates BK channel activity in cortical neurons through a
      signaling pathway that involves Trk tyrosine kinase, phospholipase C, and protein
      dephosphorylation and is calcium-dependent. Activation of BK channels may be a
      major mechanism by which neurotrophins acutely regulate neuronal activity.

PMID- 9023374
TI  - Reconstitution of stretch-activated cation channels by expression of the alpha
      subunit of the epithelial sodium channel cloned from osteoblasts.
AB  - Osteoblasts respond to repetitive strain by activating stretch-activated,
      nonselective cation channels (SA-CAT) and increasing matrix protein production.
      SA-CAT channels are thought to be responsible for mechano-transduction in
      osteoblasts, although the molecular identity of the SA-CAT channel has previously
      been unknown. We have demonstrated that both the UMR-106 osteoblast-like cell
      line and human osteoblasts in primary culture express the alpha-subunit of the
      epithelial sodium channel (alpha-ENaC). The ENaC gene product is closely related
      to a class of proteins that confer touch sensitivity to Caenorhabditis elegans
      and are referred to as degenerins. A cDNA clone was obtained of the entire coding
      region of rat alpha-ENaC (alpha-rENaC). Sequence analysis indicated that the
      osteoblast clone's sequence was identical to that originally cloned from rat
      colon. The alpha-rENaC cDNA was cloned into an expression plasmid and transfected
      into LM(TK-) cells, a null cell for SA-CAT activity. Stable transfectants
      expressed mRNA and the expected 74-kDa protein corresponding to alpha-rENaC.
      Reconstitution of alpha-rENaC resulted in the expression of a 24.2 +/- 1.0 psec
      SA-CAT channel (P(Na):P(K) = 1.1 +/- 0.1). The channel is calcium permeable
      (P(Na):P(Ca) = 1.4 +/- 0.1) and highly selective for cations over anions
      (P(Na):P(Cl) >> 20). The channel is only active after negative pressure is
      applied to cell attached patches, cell swelling, or patch excision. These results
      represent the first heterologous expression of an SA-CAT channel in a mammalian
      cell system and provide evidence that the ENaC/degenerin family of proteins are
      capable of mediating both transepithelial sodium transport and are involved in
      signal transduction by mechano-sensitive cells such as osteoblasts.

PMID- 9023375
TI  - Functional nonequality of the cardiac and skeletal ryanodine receptors.
AB  - Dihydropyridine receptors (DHPRs), which are voltage-gated Ca2+ channels, and
      ryanodine receptors (RyRs), which are intracellular Ca2+ release channels, are
      expressed in diverse cell types, including skeletal and cardiac muscle. In
      skeletal muscle, there appears to be reciprocal signaling between the skeletal
      isoforms of both the DHPR and the RyR (RyR-1), such that Ca2+ release activity of
      RyR-1 is controlled by the DHPR and Ca2+ channel activity of the DHPR is
      controlled by RyR-1. Dyspedic skeletal muscle cells, which do not express RyR-1,
      lack excitation-contraction coupling and have an approximately 30-fold reduction
      in L-type Ca2+ current density. Here we have examined the ability of the
      predominant cardiac and brain RyR isoform, RyR-2, to substitute for RyR-1 in
      interacting with the skeletal DHPR. When RyR-2 is expressed in dyspedic muscle
      cells, it gives rise to spontaneous intracellular Ca2+ oscillations and supports
      Ca2+ entry-induced Ca2+ release. However, unlike RyR-1, the expressed RyR-2 does
      not increase the Ca2+ channel activity of the DHPR, nor is the gating of RyR-2
      controlled by the skeletal DHPR. Thus, the ability to participate in skeletal
      type reciprocal signaling appears to be a unique feature of RyR-1.

PMID- 9023376
TI  - Role of leptin in hypothalamic-pituitary function.
AB  - A defect in the structure of the obese gene is responsible for development of
      obesity in the ob/ob mouse. The product of expression of the gene is the protein
      hormone leptin. Leptin causes weight loss in ob/ob and normal mice, it is
      secreted by adipocytes, and it is an important controller of the size of fat
      stores by inhibiting appetite. The ob/ob mouse is infertile and has a pattern of
      gonadotropin secretion similar to that of prepubertal animals. Consequently, we
      hypothesized that leptin might play a role in the control of gonadotropin
      secretion and initiated studies on its possible acute effects on hypothalamic
      pituitary function. After a preincubation period, hemi-anterior pituitaries of
      adult male rats were incubated with leptin for 3 hr. Leptin produced a dose
      related increase in follicle-stimulating hormone (FSH) and luteinizing hormone
      (LH) release, which reached peaks with 10(-9) and 10(-11) M leptin, respectively.
      Gonadotropin release decreased at higher concentrations of leptin to values
      indistinguishable from that of control pituitaries. On the other hand, prolactin
      secretion was greatly increased in a dose-related manner but only with leptin
      concentrations (10(-7)-10(-5) M). Incubation with leptin of median eminence
      arcuate nuclear explants from the same animals produced significant increases in
      LH-releasing hormone (LHRH) release only at the lowest concentrations tested (10(
      12)-10(-10) M). As the leptin concentration was increased, LHRH release decreased
      and was significantly less than control release at the highest concentration
      tested (10(-6) M). To determine if leptin can also release gonadotropins in vivo,
      ovariectomized females bearing implanted third ventricle cannulae were injected
      with 10 microg of estradiol benzoate s.c., followed 72 hr later by microinjection
      into the third ventricle of leptin (0.6 nmol in 5 microl) or an equal volume of
      diluent. There was a highly significant increase in plasma LH, which peaked 10-50
      min after injection of leptin. Leptin had no effect on plasma FSH concentrations,
      and the diluent had no effect on either plasma FSH or LH. Thus, leptin at very
      low concentrations stimulated LHRH release from hypothalamic explants and FSH and
      LH release from anterior pituitaries of adult male rats in vitro and released LH,
      but not FSH, in vivo. The results indicate that leptin plays an important role in
      controlling gonadotropin secretion by stimulatory hypothalamic and pituitary
      actions.

PMID- 9023377
TI  - The structure and function of a soybean beta-glucan-elicitor-binding protein.
AB  - beta-Glucan elicitor (GE), released from the cell wall of the phytopathogenic
      fungus Phytophthora megasperma by soybean glucanases, causes defense reactions in
      soybean. A GE-binding protein (GEBP) was purified from the membrane fraction of
      soybean root cells, and its cDNA was isolated. Expression of the cDNA clone in
      tobacco suspension cultured cells and in Escherichia coli conferred GE-binding
      activity to both. An antibody against the recombinant protein was found to
      inhibit the GE binding with the soybean cotyledon membrane fraction as well as
      the resulting accumulation of phytoalexin. Immunolocalization assays indicated
      that the GEBPs are located in the plasma membrane of root cells. These results
      suggest that the cDNA encodes a GE receptor and may mediate the signaling of the
      elicitor.

PMID- 9023380
TI  - The role of radiotherapy in Sweden--a landmark study by the Swedish Council on
      Technology Assessment in Health Care.

PMID- 9023379
TI  - Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci.
AB  - Using the generalized stepwise mutation model, we propose a method of estimating
      the relative mutation rates of microsatellite loci, grouped by the repeat motif.
      Applying ANOVA to the distributions of the allele sizes at microsatellite loci
      from a set of populations, grouped by repeat motif types, we estimated the effect
      of population size differences and mutation rate differences among loci. This
      provides an estimate of motif-type-specific mutation rates up to a multiplicative
      constant. Applications to four different sets of di-, tri-, and tetranucleotide
      loci from a number of human populations reveal that, on average, the non-disease
      causing microsatellite loci have mutation rates inversely related to their motif
      sizes. The dinucleotides appear to have mutation rates 1.5-2 times higher than
      the tetranucleotides, and the non-disease-causing trinucleotides have mutation
      rates intermediate between the di- and tetranucleotides. In contrast, the disease
      causing trinucleotides have mutation rates 3.9-6.9 times larger than the
      tetranucleotides. Comparison of these estimates with the direct observations of
      mutation rates at microsatellites indicates that the earlier suggestion of higher
      mutation rates of tetranucleotides in comparison with the dinucleotides may stem
      from a nonrandom sampling of tetranucleotide loci in direct mutation assays.

PMID- 9023378
TI  - Arabidopsis thaliana CBF1 encodes an AP2 domain-containing transcriptional
      activator that binds to the C-repeat/DRE, a cis-acting DNA regulatory element
      that stimulates transcription in response to low temperature and water deficit.
AB  - Recent efforts have defined a cis-acting DNA regulatory element in plants, the C
      repeat/dehydration responsive element (DRE), that stimulates transcription in
      response to low temperature and water deficit. Here we report the isolation of an
      Arabidopsis thaliana cDNA that encodes a C-repeat/DRE binding factor, CBF1 (C
      repeat/DRE Binding Factor 1). Analysis of the deduced CBF1 amino acid sequence
      indicates that the protein has a molecular mass of 24 kDa, a potential nuclear
      localization sequence, and a possible acidic activation domain. CBF1 also has an
      AP2 domain, which is a DNA-binding motif of about 60 aa present in the
      Arabidopsis proteins APETALA2, AINTEGUMENTA, and TINY; the tobacco ethylene
      response element binding proteins; and numerous other plant proteins of unknown
      function. The transcript levels for CBF1, which appears to be a single or low
      copy number gene, did not change appreciably in plants exposed to low temperature
      or in detached leaves subjected to water deficit. Binding of CBF1 to the C
      repeat/DRE was demonstrated in gel shift assays using recombinant CBF1 protein
      expressed in Escherichia coli. Moreover, expression of CBF1 in yeast was found to
      activate transcription of reporter genes containing the C-repeat/DRE as an
      upstream activator sequence but not mutant versions of the DNA element. We
      conclude that CBF1 can function as a transcriptional activator that binds to the
      C-repeat/DRE DNA regulatory element and, thus, is likely to have a role in cold-
      and dehydration-regulated gene expression in Arabidopsis.

PMID- 9023382
TI  - Palliative use of ionizing radiations.

PMID- 9023381
TI  - Radiotherapy in Sweden--a study of present use in relation to the literature and
      an estimate of future trends.
AB  - This report addresses the role of radiotherapy for treating solid tumors. It is
      based on a systematic and critical review of the scientific literature, covering
      close to 1700 published studies, involving more than 700000 patients. The report
      also compares current practice in radiotherapy with scientific evidence and
      estimates the cost of radiotherapy. The review of the literature shows there is a
      fairly solid basis for conclusions about appropriate practices in radiotherapy.
      There are about 650 studies available which are judged to be of high scientific
      quality, covering more than half a million patients. This article is a summary of
      the complete report, which appears as Supplement 6 and 7 of this issue. A third
      volume, 'Critical Issues in Radiotherapy' is available at SBU.

PMID- 9023383
TI  - A comparison of the physiological effects of RSU1069 and RB6145 in the SCCVII
      murine tumour.
AB  - The physiological and therapeutic effects of the bioreductive agent RSU1069 (80
      mg/kg i.p.) and its prodrug RB6145 (240 mg/kg i.p.) were investigated in the
      SCCVII tumour. Using laser Doppler flowmetry it was found that RSU1069 produced a
      significant 30% reduction in tumour blood flow 30 min after administration, while
      RB6145 had no effect. Tumour oxygenation, measured with an Eppendorf oxygen
      electrode, was unchanged by either agent except for a reduction in values less
      than 2.5 mmHg at 30 min after injection. Neither agent significantly altered
      tumour energy metabolism, assessed by 31P magnetic resonance spectroscopy. Both
      agents significantly increased tumour glucose content by a factor of 1.6-1.7 at
      30 min after injection, but had no effect on glucose-6-phosphate or lactate
      levels. Tumour growth was significantly delayed by heating (42.5 degrees C, 60
      min), and although neither RSU1069 nor RB6145 alone had any effect on tumour
      growth they produced a similar enhancement of the tumour response to heat. The
      therapeutic effects are consistent with the known conversion in vivo of one third
      of the pro-drug RB6145 to its active product RSU1069, however the physiological
      effects of the two agents in the SCCVII tumour are not identical.

PMID- 9023384
TI  - Prognostic significance of TGF-alpha expression in breast cancer.
AB  - A series of breast cancer biopsies from 204 women were analysed
      immunohistochemically for the expression of transforming growth factor alpha (TGF
      alpha). Expression of TGF-alpha was intense in 119 cases (58%), weak in 63 (31%),
      and totally absent in 22 (11%) of the cases. No correlation was observed between
      the expression of TGF-alpha and tumour size, metastasis at diagnosis,
      histological type and grade, ER and PR status, DNA index, S-phase fraction or the
      expression of TGF-beta1 or beta2. However, the expression of TGF-alpha was
      significantly related to axillary lymph node metastasis and to low survival
      probability during the follow-up. These data support the earlier observations on
      the in vitro studies, suggesting that TGF-alpha most probably exerts an in vivo
      growth stimulation of female breast cancer cells.

PMID- 9023385
TI  - Methodological aspects of flow cytometry DNA analysis in endometrial carcinoma,
      with special reference to sampling and reproducibility.
AB  - Two adjacent paraffin-embedded sections manifested concordance in ploidy status
      in 96% of cases (45/47), and the standard deviation (SD) for SPF was 2.7%.
      Analysis of 'micro-heterogeneity', within a distance of < or = 700 microm,
      yielded results for concordant ploidy status in 94% of cases, and the SD for SPF
      was 1.9% (n = 17). Frozen and paraffin-embedded material yielded concordant
      results for ploidy status in 87% (39/45) of cases, and SPF values were
      significantly lower (mean difference 1.5%) in the frozen samples. Diagnostic and
      repeat curettage material yielded concordant results for DNA ploidy status in 85%
      (40/47) of cases, and no significant difference in mean SPF (12% vs. 11%) was
      found. Discordant DNA ploidy results were attributable to small differences in
      the DNA histograms influencing the interpretation of near-diploid, near
      tetraploid and small non-diploid cell populations, and the influence of debris on
      SPF estimation. On the basis of our findings and the practical advantage we
      recommend paraffin-embedded material from diagnostic curettage for FCM DNA
      analysis; the results are available sooner and the handling and transportation of
      tumor samples is more convenient.

PMID- 9023386
TI  - Serum cholesterol and apolipoprotein B levels may reflect disease activity in
      ovarian cancer patients.
AB  - Data in the literature demonstrates increased receptor-mediated uptake of low
      density lipoprotein (LDL) in many types of malignant cells compared with normal
      cells. In acute leukemia, an inverse correlation has been demonstrated between
      disease activity and plasma cholesterol. To explore whether this is true also for
      ovarian cancer a case-control study was performed. We serially collected blood
      samples and assayed serum cholesterol and apolipoprotein B (the receptor
      recognizing moiety of LDL) in 10 patients with ovarian cancer. At diagnosis, the
      patients had lower mean cholesterol levels compared with 6 healthy women. An
      increase was found after primary surgery and after successful initial
      chemotherapy. The 5 patients who are in complete remission after a mean follow-up
      time of 79 months had higher cholesterol and apolipoprotein B levels at their
      last visit than at diagnosis. In contrast, a reduction of the two analytes was
      found in the patients who died from their ovarian cancer 15 to 28 months after
      diagnosis. The results may open a possibility for targetted chemotherapy in
      ovarian cancer with LDL as a drug carrier.

PMID- 9023387
TI  - Changes in radiation sensitivity and steroid receptor content induced by hormonal
      agents and ionizing radiation in breast cancer cells in vitro.
AB  - Possible influences of tamoxifen and estradiol on in vitro radiation sensitivity
      and cellular receptor content after irradiation and/or tamoxifen treatment were
      studied in breast cancer cell lines; estrogen receptor (ER) and progesterone
      receptor (PgR) positive cell lines MCF-7 and MCF-7/TAM(R)-1 and the ER and PgR
      negative cell line MDA-MB-231. The tamoxifen resistant MCF-7/TAM(R)-1 cells were
      more resistant to ionizing radiation than the MCF-7 and MDA-MB-231 cells.
      Exposure to tamoxifen made the MCF-7 cells more radiation resistant, while
      estradiol made the MDA-MB-231 cells more radiation sensitive. A radiation dose of
      6 Gy reduced the ER content in cytosol in both MCF-7 and MCF-7/TAM(R)-1 cells,
      but brought no alterations to the PgR content. In MCF-7/TAM(R)-1 cells tamoxifen
      exposure significantly increased the ER and reduced the PgR content, an effect
      not observed in the MCF-7 cells. To conclude, the present study indicates that
      irradiation and tamoxifen may modify the ER and PgR content in cytosol in breast
      cancer cells. Hormonal treatment may alter the radiation sensitivity, even in ER
      negative cells, suggesting that hormonal agents may act both via receptor and non
      receptor binding mechanisms.

PMID- 9023388
TI  - Skin treatment with bepanthen cream versus no cream during radiotherapy--a
      randomized controlled trial.
AB  - In several radiotherapy departments, dexpanthenol cream (Bepanthen 'Roche') has
      been used extensively to ameliorate acute radiotherapy skin reactions. The
      evidence base for this practice is obscure as no randomized trials have been
      performed. In the present clinical prospective study of 86 patients we have
      compared Bepanthen cream with no topical ointment at all. The cream was applied
      on randomly selected parts of treatment fields in laryngeal and breast cancer
      patients, and so each patient acted as his own control. Seven patients were
      withdrawn from analysis. Scoring of skin reactions in 16 laryngeal and 63 breast
      cancer patients was performed without knowledge of which area that had been given
      cream or not. Endpoints were a modified skin reaction grading according to
      EORTC/RTOG, and itching/pain in treated fields. The study did not indicate any
      clinically important benefits of using Bepanthen cream for ameliorating
      radiogenic skin reactions under the conditions applied.

PMID- 9023389
TI  - Cervical cytology: perspectives from both sides of the Atlantic.

PMID- 9023390
TI  - Is cervical screening working? A cytopathologist's view from the United Kingdom.
AB  - This article considers the NHS cervical screening program and the controversies
      which have attended the introduction of comprehensive screening in a partially
      screened population of women in whom the underlying risk of disease was unknown.
      The increase in screening coverage which has taken place since 1988 has coincided
      with a period of high prevalence of cervical cancer and its precursors among
      women in the screening age group, against which background the recent fall in
      mortality and incidence of the disease has been a far greater achievement than
      generally recognized. The success of the program is considered in the context of
      the expectations and limitations of the test itself, and the high standards
      required for screening to be effective.

PMID- 9023391
TI  - Gastric epithelial dysplasia and adenoma: historical review and histological
      criteria for grading.
AB  - Gastric epithelial dysplasia (GED) hypothetically is a straight-forward concept:
      dysplastic epithelium replacing the normal gastric epithelium of the stomach.
      However, since its inception several decades ago, the term GED has become
      progressively complex and confusing because of differences in definitions and
      nomenclature that have been based on cytological, microscopic, endoscopic, or
      gross features. This has resulted in the terms "dysplasia," "adenoma," "flat
      adenoma," and "depressed adenoma." Some authors have also included reactive
      changes under the term "dysplasia."

PMID- 9023393
TI  - The extent and multicentricity of high-grade prostatic intraepithelial neoplasia
      in clinically localized prostatic adenocarcinoma.
AB  - High-grade prostatic intraepithelial neoplasia (PIN) is considered the most
      likely precursor of invasive prostatic adenocarcinoma, and is characterized by
      cellular proliferations within preexisting ducts and glands with cytological
      changes mimicking cancer. The extent and multicentricity of this clinically
      important histopathologic lesion have not been fully defined. We sought to
      determine whether the extent and zonal distribution of PIN are related to
      prostate cancer. A total of 195 whole-mounted radical prostatectomy specimens
      were evaluated. All patients had clinically localized cancer, and none had
      received preoperative therapy. The zonal location and multicentricity of PIN were
      recorded, and the volume of PIN was measured using a grid-counting method
      according to pattern (tufting, micropapillary, cribriform, and flat) and spatial
      proximity to cancer (less than or equal to 2 mm from cancer, and greater than 2
      mm from cancer). The results were correlated with patient age, prostate volume,
      cancer volume, pathological stage, and Gleason grade. High-grade PIN was
      identified in 86% of cases, usually with multiple architectural patterns of PIN
      in each positive case: tufting (97% of cases), micropapillary (66% of cases),
      cribriform (19% of cases), and flat (21% of cases). The mean volume of PIN was
      1.32 cm3 (standard error [SE], 0.10; range, 0 to 8.12 cm3), and was greater for
      PIN within 2 mm of cancer (mean, 1.0 cm3) than for PIN more than 2 mm from cancer
      (mean, 0.3 cm3). PIN was usually multicentric (64.5% of cases) and located in the
      nontransition zone (63%) or all zones (36%) of the prostate. There was a positive
      correlation of total volume of PIN and volume of cancer, but this correlation was
      significant only for PIN within 2 mm of cancer. The volume of PIN was positively
      correlated with age, pathological stage, and Gleason score; most of these
      positive correlations were caused by PIN within 2 mm of cancer rather than that
      greater than 2 mm from cancer. Our results indicate that the extent and zonal
      distribution of high-grade PIN and carcinoma are strongly associated, and that
      PIN is frequently multicentric. This supports the hypothesis that PIN is a
      premalignant lesion.

PMID- 9023392
TI  - Relevance of cytogenetic and fluorescent in situ hybridization analyses in the
      clinical assessment of soft tissue sarcoma.
AB  - Soft tissue sarcomas are a heterogeneous group of malignant tumors displaying a
      wide range of clinical presentations, morphological features, and biological
      behaviors. These characteristics and the recent development of differentiated
      treatment regimens for the different types of soft tissue sarcomas call for
      refined histological classification using additional ancillary approaches such as
      cytogenetic and molecular genetic analyses. We coupled classical cytogenetics and
      fluorescent in situ hybridization (FISH) on both metaphases and interphase nuclei
      to show the feasibility of this approach to characterize tumor type-specific
      chromosome rearrangements in soft tissue sarcomas of different histotype. In 35
      cases analyzed, we detected the presence of specific chromosome rearrangements
      such as t(X;18) in synovial sarcoma (SS), t(12;16) in myxoid liposarcoma (MLS),
      t(11;22) in peripheral primitive neuroectodermal tumors (pPNET), t(2;13) in
      alveolar rhabdomyosarcoma (ARMS) and ring chromosomes in dermatofibrosarcoma
      protuberans (DFSP). In several cases, the presence of these cytogenetic
      rearrangements was of help for a differential diagnosis. The FISH analysis using
      painting probes not only confirmed the cytogenetic results but also allowed the
      identification of tumor-specific chromosome changes in those cases presenting low
      mitotic index or with poor quality chromosomes. Moreover, in the absence of
      analysable metaphases, FISH was successfully performed on interphase nuclei.
      Taken together, these results indicate both the diagnostic and clinical relevance
      of a molecular cytogenetic analysis in the study of soft tissue sarcomas.

PMID- 9023394
TI  - Pancreatic-polypeptide cell hyperplasia associated with pancreatic or duodenal
      gastrinomas.
AB  - An immunohistochemical investigation of pancreatic-polypeptide (PP) cells in the
      PP-rich region of the pancreas, of ventral embryological origin, was performed in
      three female patients affected by or previously operated on for functioning
      duodenal or pancreatic gastrinomas not associated with multiple endocrine
      neoplasia syndrome. A pronounced PP-cell hyperplasia showing histological
      patterns of endocrine cell dysplasia and focal adenomatosis as defined by Jaffe
      et al was found in all cases. Morphometric analysis showed that in these patients
      the fraction of ventral-type pancreatic lobules occupied by PP-immunoreactive
      cells was 14.77 +/- 5.73%, 8.94 +/- 2.92%, and 10.83 +/- 5.64%, respectively.
      These values were three to five times higher than the upper values found in
      controls (mean, 2.20%; range, 1.54 to 2.93%; P < .0001). PP-cell hyperplasia may
      contribute for the increased circulating levels of PP found in gastrinoma
      patients. In this regard, elevation of fasting blood PP was found in one of four
      determinations done in one patient, indicating that PP-cell hyperplasia may be
      responsible for, at least, transient PP hypersecretion. In one of our patients,
      PP-cell hyperplasia was found 15 years after normalization of gastrin levels by
      removal of a single pancreatic gastrinoma. This finding is against a trophic role
      for hypergastrinemia in the development of PP-cell hyperplasia. In one of two
      patients in whom the pancreatic regions of dorsal embryological origin (ie, body
      and tail of the gland) were examined, ventral-type, PP-rich islets were
      frequently encountered, a finding at variance with their exceptional detection in
      control cases. This finding suggests that PP cell hyperplasia of the PP-rich
      pancreatic region may be a feature of a more diffuse disorder of PP cell
      development in the pancreas of gastrinoma patients.

PMID- 9023395
TI  - Detection of the Mbcr/abl translocation in chronic myeloid leukemia by
      fluorescence in situ hybridization: comparison with conventional cytogenetics and
      implications for minimal residual disease detection.
AB  - The correlation between the detection of the Philadelphia chromosome by
      conventional cytogenetics and the identification of Mbcr/abl translocation by
      fluorescence in situ hybridization (FISH) in both metaphase and interphase cells
      is prospectively analyzed in a group of 21 chronic myeloid leukemia (CML)
      patients. To gain insight into the sensitivity and specificity of the detection
      of the bcr/abl translocation by FISH, a group of 10 healthy volunteers was also
      studied. Our results show that for the detection of bcr/abl translocation in CML
      patients, FISH is more sensitive than conventional cytogenetics because it
      detects significantly higher proportions of cells carrying the translocation both
      in metaphase (P < .0002) and interphase nuclei (P < .003). Moreover, in the
      metaphases of the controls analyzed, no bcr/abl+ chromosome was detected that
      makes the colocalization of bcr and abl signals in the CML patients highly
      specific. Conversely, in control interphase nuclei, a small proportion of cells
      (ranging between 0% and 3%, mean value of 1.7% +/- 0.9%) displaying
      colocalization of both signals is usually detected. This limits, at least for the
      moment, the routine use of FISH for the detection of minimal residual disease in
      CML patients at levels lower than 10(-1).

PMID- 9023396
TI  - Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in
      gastrointestinal stromal tumors.
AB  - The DNA content and proliferative index of 61 gastrointestinal stromal tumors
      (GIST) were measured by image analysis and correlated with the lesion's
      clinicopathological features and patient's survival. DNA analysis was performed
      on cytospin single-cell preparations obtained from the paraffin-embedded tissue
      blocks. MIB-1 was the proliferation marker used on paraffin sections. DNA
      aneuploidy was detected in 12 tumors (18%), and high MIB-1 index (>22%) in 12
      lesions (18%). DNA aneuploidy and high MIB-1 index statistically correlated with
      high mitotic rate (> or = 5 x 10 high-power field [HPF]) (P < .001) and with the
      presence of necrosis (P < .05). The patient's survival was significantly
      correlated with DNA ploidy (P < .01), MIB-1 index (P < .00001), mitotic rate (P <
      .00001), presence of necrosis (P < .0001), and size of the tumor (P < .01).
      Multivariate regression analysis showed that only MIB-1 index was an independent
      parameter in predicting the clinical outcome for patients with GIST. The mitotic
      rate was the only other independent prognostic factor when MIB-1 index was not
      allowed to enter the model.

PMID- 9023397
TI  - B-cell gene rearrangement in benign and malignant lymphoid proliferations of
      mucosa-associated lymphoid tissue and lymph nodes.
AB  - The polymerase chain reaction (PCR) with polyacrylamide gel electrophoresis was
      used to study patterns of immunoglobulin heavy chain (IgH) gene rearrangement
      (GR) in formalin-fixed, paraffin-embedded specimens of lymphomas and reactive
      conditions of mucosa-associated lymphoid tissue (MALT) and lymph node. DNA
      amplification was performed directly on sections obtained from paraffin blocks.
      Five patterns of PCR products were observed: a single band, two or more discrete
      bands, smearing, a single band overlying a smear, and two or more bands over a
      smear. A pure polyclonal pattern (smear) was observed in all of the reactive
      lymph nodes but in only 15% of cases of Helicobacter pylori (HP) gastritis with
      lymphoid hyperplasia, 25% of cases of HP gastritis without lymphoid hyperplasia,
      and 37% of colonic specimens of various types. Patterns consisting of multiple
      bands with or without background smearing were common in gastritis, colitis, and
      gastric lymphomas. Single bands or dominant bands were present in all lymph node
      and salivary gland lymphomas, 12 of 14 cases of gastric lymphoma, and 17 of 20
      cases of HP gastritis with lymphoid hyperplasia. These bands were reproducible in
      deeper sections from the same paraffin block or similar areas sampled in
      different blocks in all of the lymph node and salivary gland lymphomas, 11 of 12
      gastric lymphomas, but only 1 of 17 cases of HP gastritis with lymphoid
      hyperplasia. Bands were also found in 3 of 20 cases of HP gastritis without
      lymphoid hyperplasia and 17 of 38 colonic specimens, but these were not
      reproducible. The complexity of patterns of IgH GR in acquired MALT compared with
      lymph nodes may be the result of a relative paucity of B-cell clones or
      preferential proliferation of B-cell clones with a limited area of distribution.

PMID- 9023398
TI  - Low prevalence of human papillomavirus infection in esophageal squamous cell
      carcinomas from North America: analysis by a highly sensitive and specific
      polymerase chain reaction-based approach.
AB  - Several studies have documented the frequent occurrence of human papillomavirus
      (HPV) DNA in esophageal squamous cell carcinomas (ESCC) in patients from
      geographic regions where the incidence of this type of cancer is high, such as
      parts of China. However, the prevalence of HPV infection in ESCC in patients from
      low incidence geographic regions, such as North America, remains controversial.
      Therefore, this study evaluates the prevalence of HPV in ESCC in patients from
      North America, a region where the population is considered at low risk for the
      development of this neoplasm. ESCCs in 51 patients from three North American
      cities were analyzed for the presence of HPV DNA by a highly sensitive and
      specific polymerase chain reaction (PCR) method. Tumor DNA was extracted from
      formalin-fixed, paraffin-embedded tissue specimens and assayed by PCR using an L1
      HPV consensus sequence primer, as well as HPV 16 and HPV 18 E7 region primers.
      The use of consensus primers to the L1 region allows for detection of most known
      HPV types and many novel HPV types. Appropriately sized reaction products were
      analyzed by restriction fragment length polymorphism (RFLP) to confirm the
      presence and type of HPV, and to exclude products produced by amplification of
      human DNA sequences. After complete analysis, only one case (2%) of ESCC was HPV
      DNA positive. This case was independently confirmed using L1 and E7 consensus
      primers as HPV type 16 and was the only case that tested positive with either
      assay. These results show that, in contrast to geographic regions where ESCC is
      prevalent, HPV infection occurs infrequently in association with ESCC in patients
      from North America.

PMID- 9023399
TI  - The potential role of mast cells in lung allograft rejection.
AB  - To perform a retrospective pilot study of the potential role of mast cells in
      acute and chronic rejection of the lung allograft, transbronchial biopsies of 29
      patients with acute rejection and six patients with bronchiolitis obliterans were
      stained with antibodies to mast cell tryptase. The number of mast cells per unit
      area were counted, and compared with a control group of normal lung biopsies
      stained in a similar fashion. Increasing grades of acute rejection were
      associated with progressively more mast cells per high-power microscopic field.
      The presence of bronchiolitis obliterans was accompanied by the greatest numbers
      of mast cells. Mast cells may play a role in the acute rejection response to the
      lung allograft and in the development of bronchiolitis obliterans.

PMID- 9023400
TI  - Distribution of extracellular matrix components in adamantinoma of long bones
      suggests fibrous-to-epithelial transformation.
AB  - Adamantinoma of long bones is a rare skeletal tumor of unknown origin with
      epithelial and fibrous elements. The ill-defined distinction between the two
      components in some cases earlier led to the assumption that these might be
      derived from the same (mesenchymal) stem cell. In this study, we investigated the
      distribution of extracellular matrix components in 21 adamantinomas by
      immunohistochemistry, to gain information on the interaction between the
      epithelial and fibrous parts of the tumor. Collagens I and III, and fibronectin
      were generally present in the (osteo-)fibrous tissue of adamantinoma but lacked
      in the epithelial aggregates. There was a clear relation between the
      identification of the epithelial and fibrous components at the histological
      level, and the staining for basement membrane proteins collagen IV and laminin.
      Prominent areas with cohesive epithelial growth were surrounded by continuous
      basement membranes, whereas less distinct epithelial islands contained membrane
      interruptions or had no surrounding basement membrane at all. Tenascin stained
      intensely surrounding demarcated epithelial aggregates, but weakly or absent more
      distantly. Osteofibrous dysplasia (OFD)-like tumors displayed local spicular
      density or pericellular staining of basement membrane factors in fields of
      isolated keratin-positive cells. These findings suggest that in adamantinoma
      individual epithelial cells transform from the osteofibrous tissue and thereafter
      form clusters of epithelium, as can be recognized in classic adamantinoma. This
      is in analogy to the development of the glandular component of biphasic synovial
      sarcoma. The fibrous part of adamantinoma is, however, believed to be of benign
      nature. These results further substantiate the hypothesis of osteofibrous
      dysplasia being a potential precursor lesion of adamantinoma.

PMID- 9023401
TI  - Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung.
AB  - In lung carcinomas, the proliferative activity, as detected by Ki-67 antigen
      immunostaining of surgical specimens, is a valuable factor predicting clinical
      evolution and response to treatment. We investigated whether bronchial endoscopic
      and fine-needle aspiration (FNA) biopsies of lung carcinoma can provide a
      reliable estimation of the tumor proliferative fraction (TPF). In 66 resectable
      lung carcinomas, sections of preoperative bronchial or FNA biopsies and the
      corresponding surgical specimens were stained in parallel for Ki-67 using MIB-1
      monoclonal. The mean TPF was 44.7% in the surgical specimens, 40.3% in bronchial
      biopsies, and 26.3% in FNAs. When the scores of biopsy and resected specimen of
      each individual tumor were compared, a significant correlation between the TPFs
      of preoperative and postoperative specimens was found (r = .79). In both biopsy
      and surgical specimens, a high TPF was associated with squamous cell carcinoma
      histological type and high-grade (poorly differentiated) tumors. In addition, a
      significantly (P < .05) lower disease-free interval was found in patients
      affected by highly proliferating tumors (irrespective of the tumor stage). We
      conclude that the proliferative activity of lung cancer can be reliably assessed
      in bronchial or FNA biopsies. This information could help to select chemotherapy
      protocols in nonresectable lung carcinomas.

PMID- 9023402
TI  - Distribution of endothelin immunoreactivity in human kidney correlates with
      antemortem acute renal failure: a possible postmortem immunohistochemical test.
AB  - The role of endothelin in the normal kidney function, as well as in disease
      states, has been studied in animal models. In addition, it was shown previously
      that endothelial, mesangial, and epithelial components of the nephron produce
      endothelins, in particular ET-1. We performed immunohistochemistry for ET-1
      reactivity on 31 autopsy and four surgically removed kidneys. Eighteen cases had
      clinical diagnoses of acute renal failure (ARF) In the remaining 17 cases with
      normal or unchanged renal function before death or surgery, ET-1 immunoreactivity
      was present in tubular epithelium, with the most intense staining in the
      medullary collecting tubules. In 13 of 18 cases of ARF, tubular staining was
      either replaced or accompanied by interstitial reactivity in the inner and outer
      medulla, corresponding to the location of the vasa recta and interlobular
      arteries identified by factor VIII immunostaining. Controlled autolysis performed
      on normal kidney over 72 hours postmortem produced tubular epithelial degradation
      with reduced epithelial cell endothelin reactivity, but not an interstitial
      pattern. In situ hybridization for ET mRNA localized expression to tubular and
      collecting duct epithelium in both normal and acute renal failure cases. The
      change in the localization of ET-1 immunoreactivity from tubular epithelium to
      the interstitium in these ARF cases does not appear to be the result of increased
      vascular endothelial production of endothelin. This altered immunoreactivity
      pattern for ET-1 may be a marker of antemortem tubular damage and can be used as
      an adjunct in the autopsy diagnosis of ARF.

PMID- 9023403
TI  - Malignancy after retinoblastoma: secondary cancer or recurrence?
AB  - The risk of second malignancy after retinoblastoma is reported to be as high as
      20% at 10 years after initial diagnosis. This incidence may be an overestimate
      because of difficulties in distinguishing a second malignancy from recurrent
      tumor. We encountered a patient with bilateral retinoblastoma who developed a
      temporal mass 3.5 years after initial treatment for what had first been diagnosed
      as rhabdomyosarcoma; further study suggested that it was recurrent retinoblastoma
      manifesting as primitive neuroectodermal tumor (PNET) with multilineage
      differentiation. Chromosome 13 abnormalities were compatible with either
      rhabdomyosarcoma or recurrent retinoblastoma. To determine how often second
      malignancies in retinoblastoma patients may be confused with recurrent primary
      tumor, we reviewed our experience at Children's Hospital of Pittsburgh. Of 43
      retinoblastoma patients seen between 1951 and 1992, presumed second malignancies
      were documented in four, including the current case. Of the three other second
      tumors, one had both neural and skeletal muscle differentiation; another was
      diagnosed as rhabdomyosarcoma unclassifiable as embryonal or alveolar; the last
      was an osteosarcoma. Only the osteosarcoma was clearly a second neoplasm; two and
      perhaps three of the other cases may be recurrent retinoblastoma. The distinction
      between second malignancy and recurrent retinoblastoma may be difficult but is
      worth determining, because treatment may differ, depending on the correct
      designation.

PMID- 9023404
TI  - Endothelial and macrophage upregulation of urokinase receptor expression in human
      renal cell carcinoma.
AB  - The binding of urokinase-type plasminogen activator (u-PA) to a specific cell
      surface receptor (uPA-R) has been shown to enhance plasminogen activation, a
      process involved in extracellular matrix degradation and cell migration during
      angiogenesis and tumor growth. We investigated the expression of u-PA and uPA-R
      in renal cell carcinomas (n = 11). By immunohistochemistry using monoclonal and
      polyclonal anti-uPA-R antibodies, we found that tumoral capillary endothelial
      cells (von Willebrand factor and CD31 positive cells) overexpressed uPA-R,
      whereas vascular endothelial cells of the normal human kidney do not. In
      addition, tumor-associated macrophages (CD68-positive cells) strongly expressed
      uPA-R. In contrast, few tumoral cells and stromal fibroblasts expressed uPA-R. By
      in situ hybridization using a cDNA S35-labeled probe specific for uPA-R, we
      confirmed the local expression of uPA-R messenger RNA. We also detected the
      induction of u-PA in tumoral capillary endothelial cells and in tumor-associated
      macrophages. In two cases, tumoral cells themselves were also stained by anti-u
      PA antibodies in focal areas. Finally tissue-type plasminogen activator (t-PA)
      was also overexpressed by tumoral capillary endothelial cells as compared with
      endothelial cells of normal human kidney vessels. These findings indicate an
      active invasive phenotype of endothelial cells in renal cell carcinoma and
      suggest a role for the plasminogen activation system in tumoral angiogenesis and
      invasion.

PMID- 9023405
TI  - Microsatellite alterations indicating monoclonality in atypical hyperplasias
      associated with breast cancer.
AB  - One model of breast tumorigenesis postulates a sequential evolution from normal
      to proliferative epithelium and eventually to neoplasia, but genetic data to
      support this progression have been limited. We wished to determine whether
      atypical hyperplasia (AH), a proliferative lesion conventionally classified and
      treated as benign, but associated with an increased risk of developing carcinoma,
      might show evidence of genetic abnormalities. Using the polymerase chain reaction
      (PCR), we examined DNA extracted from 12 separate AH lesions, from six breast
      cancer patients' paraffin-embedded tissue specimens, for alterations in
      microsatellite repeat sequences. Five of 12 AH lesions, from three of six
      patients, demonstrated alterations in microsatellite sequences in patterns
      indicating that the AH lesions are monoclonal or contain a substantial monoclonal
      component. We conclude that a subset of AH lesions from patients with breast
      cancer are characterized by monoclonal microsatellite alterations; therefore,
      they may already be neoplastic. This finding lends support to one postulated
      sequence of breast tumorigenesis and suggests that some type of genetic
      instability may play a role early in breast tumor development.

PMID- 9023406
TI  - Expression of messenger RNAs for metalloproteinases 2 and 9, type IV collagen,
      and laminin in nonneoplastic and neoplastic endometrium.
AB  - In this study, we analyzed the messenger RNA (mRNA) synthesis of matrix
      metalloproteinases (MMPs) 2 and 9, and their main substrates laminin and type IV
      collagen by in situ hybridization in nonneoplastic, hyperplastic, and neoplastic
      endometrial tissues. In nonneoplastic endometrium stromal synthesis of MMP2,
      laminin and type IV collagen messenger RNA (mRNA) could be detected throughout
      the cycle. Their synthesis was strongest in the late secretory and decidualized
      endometrium. In epithelial cells, only laminin mRNA synthesis was observed. MMP9
      mRNA was expressed in only stromal and epithelial cells of the decidualized
      endometrium. In hyperplastic and neoplastic endometrium, the expression of MMP2,
      MMP9, laminin, and type IV collagen mRNA was variably present in stromal cells,
      whereas epithelial cells expressed only laminin mRNA, except for one case of a
      grade III carcinoma, which also showed signals for MMP2 and MMP9 mRNAs in the
      carcinoma cells. The presence of MMP2, laminin, and IV collagen mRNA in normal
      endometrium reflects their importance in the tissue response and matrix
      remodeling during the proliferative and secretory phases of the menstrual cycle.
      Their mRNA synthesis follows a similar pattern, suggesting that it is associated
      with hormonal changes during the menstrual cycle. According to the results, MMP9
      does not participate in tissue remodeling during the secretory or proliferative
      phases, but like MMP2, it is found in the neoplastic endometrial stroma,
      suggesting that it contributes to the invasion of malignant endometrial cells.

PMID- 9023407
TI  - Hamartomas in the setting of chronic epilepsy: a clinicopathologic study of 13
      cases.
AB  - Hamartomas are a poorly defined group of lesions and a rare cause of chronic
      epilepsy. We studied 13 patients, nine males and four females, whose cause of
      seizures was attributed to a hamartoma. The patients ranged in age from 6 to 33
      years (mean, 21 years). Seizure duration before surgery ranged from 1.5 to 22
      years (mean, 10 years). Seven hamartomas were located on the right side and six
      on the left. Six were located in the frontal lobe, five in the temporal lobe, and
      two in the occipital lobe. Twelve patients underwent gross total resection of the
      lesion and one a partial resection. All consisted of a circumscribed,
      disorganized collection of glial cells, primarily astrocytes. Rarely a neuronal
      component was admixed. One lesion contained an increased number of small blood
      vessels. Eight (62%) hamartomas contained eosinophilic granular bodies, and focal
      microcalcification was observed in three lesions (23%). Adjacent cortical
      architectural abnormalities (cortical dysplasia) were identified in eight (62%)
      resection specimens. Necrosis, mitoses, and prominent cytological atypia were
      absent in all lesions. Differential diagnostic considerations include low grade
      astrocytoma, ganglioglioma, dysembryoplastic neuroepithelial tumor, and cortical
      dysplasia. Postoperatively, 10 patients (77%) had complete resolution or greater
      than 90% reduction of seizure frequency. Two patients (16%) developed recurrent
      seizures 8 and 13 months postoperatively. One patient who underwent a partial
      resection showed no decrease in seizure frequency. No lesion recurrence on
      imaging studies has been observed in the 12 patients who underwent gross total
      resection of their hamartoma during 1 to 51 months (mean, 14 months) follow-up.
      We conclude that hamartomas seen in the setting of chronic epilepsy are generally
      low-grade lesions that respond well to gross total resection. Circumscription and
      lack of significant cytological atypia help distinguish these lesions from other
      neoplastic causes of epilepsy. Hamartomas that arise in the setting of chronic
      epilepsy appear to be associated with increased incidence of cortical
      architectural abnormalities (cortical dysplasia) and represent maldevelopmental
      lesions.

PMID- 9023408
TI  - Prognostic value of p53 in non-small cell lung cancer: relationship with
      proliferating cell nuclear antigen and cigarette smoking.
AB  - p53 mutations are among the most frequent genetic alterations reported in human
      lung cancer. Although the prognostic value of altered p53 expression is still
      debated, it is accepted widely that estimation of the proliferation rate has an
      important prognostic role. Moreover, an association between certain types of
      human lung cancers and tobacco use is well known. Drawing from this background,
      we investigated the immunohistochemical expression of mutant oncogenic p53
      protein, and related it to the smoking history of 61 patients with non-small cell
      lung carcinoma (NSCLC) and to the expression pattern of proliferating cell
      nuclear antigen (PCNA), which is considered to be an important negative
      prognostic factor in several neoplasms. We found p53 overexpression in 22 (36.1%)
      specimens, including 16 squamous carcinomas (41%) and six (27.2%)
      adenocarcinomas. PCNA nuclear staining was detected in 98.4% of the specimens,
      and a significantly higher PCNA expression score was found in all of the p53
      positive samples. When the patient survival time was compared, p53 accumulation
      had a statistically significant negative prognostic value (P < .001). This was
      supported by a Kaplan-Meier survival percentage plot of immunohistochemically p53
      undetectable specimens and p53-detectable specimens. These latter patients had a
      greatly reduced survival time. A relationship was established between p53
      immunohistochemical detection and the smoking history of the patients. None of
      the specimens from the nonsmoking patients expressed immunohistochemically
      detectable p53 protein. Altered p53 expression was detected in 40.7% of smoking
      patients. Our findings support the hypothesis of involvement of p53 mutations in
      tobacco-induced carcinogensis and indicate that altered p53 expression plays an
      important prognostic role in NSCLC in smokers.

PMID- 9023409
TI  - T- and T/natural killer-cell lymphomas of the salivary gland: a
      clinicopathologic, immunohistochemical and molecular study of six cases.
AB  - Primary salivary gland lymphomas are almost always of B lineage, with most being
      represented by low grade B-cell lymphoma of mucosa-associated lymphoid tissue.
      This study characterizes the rare non-B-cell lymphomas of the salivary gland
      based on an analysis of six cases. All patients were men, with a mean age of 53.5
      years. They presented with submandibular or parotid mass, which on histological
      examination showed extensive interstitial infiltration by small, medium-sized, or
      large lymphoid cells. There was prominent invasion and expansion of the ducts and
      acini in five cases. Angioinvasion was evident in two cases. Three cases were of
      T lineage and were CD56 negative; one of these cases expressed CD30. Three cases
      showed an immunophenotype of CD2+ CD3(f)- CD3(p)+ CD56+, consistent with
      T/natural killer (NK) cell lymphoma. In situ hybridization for Epstein-Barr virus
      (EBV)-encoded early nuclear RNA (EBER) showed positive reaction exclusively in
      the three CD56+ cases. Clonal T-cell populations were shown in two CD56-negative
      cases by polymerase chain reaction on paraffin sections using primers for the T
      cell-receptor (TCR) gamma-chain gene, but not in the other four cases (the three
      CD56+ cases and one CD56- case). Four patients (two CD56+ and two CD56-) died
      within 3 years, and two were disease free at 4 and 1.5 years, respectively. This
      study shows that salivary gland T- or T/NK-cell lymphomas cannot be reliably
      distinguished from B-cell lymphomas on morphological grounds alone, because both
      can show prominent lymphoepithelial lesions. It appears that T/NK-cell lymphomas,
      which are often extranodal in localization and strongly associated with Epstein
      Barr virus (EBV), show a predilection to involve the salivary glands as well.

PMID- 9023410
TI  - Cerebral palsy and thrombi in placental vessels of the fetus: insights from
      litigation.
AB  - Fetal vessels in the placentas of 11 of 15 infants with cerebral palsy contained
      thrombi. An alternate basis for the injury was identified in the four placentas
      without thrombi. Autopsy findings in one infant who died at age 1 month confirmed
      the presence of cerebral thrombi and infarcts. It is concluded that thrombotic
      events in utero may explain the pathogenesis of many instances of cerebral palsy
      and that identification of a coagulopathy in parents could potentially identify
      those at risk and provide a basis for preventive treatment during pregnancy.

PMID- 9023411
TI  - Perinodular hydropic degeneration of a uterine leiomyoma: a diagnostic challenge.
AB  - Perinodular hydropic degeneration of a uterine leiomyoma is a rare form of the
      more common hydropic change observed in leiomyomas. With minimal discussion in
      the surgical pathology literature, appropriate evaluation may be challenging
      because the differential diagnosis includes other uncommon uterine disorders such
      as intravenous leiomyomatosis, diffuse leiomyomatosis, myxoid leiomyosarcoma,
      endometrial stromal sarcoma, angiofibroma, and angiomyxoma. We describe such a
      diagnostic challenge in a 42-year-old woman with a left adnexal mass discovered
      during an annual examination. With only three cases of perinodular hydropic
      degeneration previously reported, this case is the first with extrauterine
      extension and was initially concerning for a more aggressive process.

PMID- 9023412
TI  - Blood cyst of the pulmonary valve in an adult: report of a case and review of the
      literature.
AB  - We report a case of a blood cyst originating from the pulmonary valve cusp of a
      43-year-old Japanese woman with pulmonary stenosis. Cineangiography revealed a
      pedunculated tumor on the arterial surface of the pulmonary valve. It was
      successfully removed by a transpulmonary artery approach. The cyst contained old
      blood and calcified thrombi, and its wall consisted of collagenous fibrous
      tissue. Immunohistochemically, a monolayer of flat cells lining the cyst was
      confirmed as endothelium using antibodies to von Willebrand factor and CD34, as
      well as UEA-I lectin. To the best of our knowledge, blood cysts of the pulmonary
      valve are rare and only 10 such cases have been reported, including six pediatric
      cases. This case is the oldest and fifth adult patient with a blood cyst found on
      the pulmonary valve. A possible histogenesis is discussed.

PMID- 9023413
TI  - Aneurysmal cyst of soft tissue: report of a case with serial magnetic resonance
      imaging and biopsy.
AB  - We report a case of an extraosseous aneurysmal cyst arising in the left
      retroclavicular soft tissue of a 29-year-old woman. A magnetic resonance imaging
      (MRI) scan showed a solid lesion within soft tissue, abutting the clavicle
      without bone involvement. An incisional biopsy was interpreted as showing
      osteoclast rich nodular fasciitis with prominent vascularity. A second MRI 5
      months later showed intralesional cystic change with areas of increased signal on
      T2-weighted images, still without any bony defect. The lesion was excised.
      Histological examination revealed large vascular spaces lined focally by giant
      cells. The remainder of the lesion was composed of an admixture of spindle cells
      and osteoclast-like giant cells. The histological and ultrastructural appearance
      was that of an aneurysmal bone cyst; however, in view of the lack of any bony
      involvement, a diagnosis of aneurysmal cyst of soft tissue was made. Primary
      aneurysmal cysts of soft tissue are rare; this is the third well-documented case
      in the literature, and the first to describe both the MRI appearance and the
      histological evolution from a solid to multiloculated lesion.

PMID- 9023414
TI  - Interlaboratory reproducibility of the interpretation of flow cytometric DNA
      histograms.

PMID- 9023415
TI  - HLA-A locus-restricted and tumor-specific CTLs in tumor-infiltrating lymphocytes
      of patients with non-small cell lung cancer.
AB  - HLA class I restriction and tumor specificity of cytotoxicity in the IL-2
      activated tumor-infiltrating lymphocytes from 16 patients with non-small cell
      lung cancer were investigated. Six HLA class I-restricted and tumor-specific CTL
      lines were established: (i) HLA A2-restricted and adenocarcinoma-specific CTLs in
      three (two A0201+ and one A0206+) patients with adenocarcinoma, (ii) HLA A3101-
      and A3302-restricted and adenocarcinoma-specific CTLs in an HLA A3101/3302+
      patient with adenocarcinoma, and (iii) HLA A3302-restricted CTLs and (iv) HLA
      A2402-restricted CTLs recognizing tumors with different types of histology in an
      HLA A3302+ patient with adenocarcinoma and an HLA A2402+ patient with squamous
      cell carcinoma (SCC), respectively. The three HLA A2-restricted CTL lines
      recognized 4, 4, or 6 of 15 HLA A2+ adenocarcinoma cell lines that originated
      from lung, stomach, colon, and breast with different subtypes (HLA A0201, A0206,
      and A0207), respectively. Furthermore, the CTLs of an HLA A0206+ patient
      recognized five different fractions of peptides eluted from an HLA A0201+
      adenocarcinoma cell line. These results showed evidence of the existence of HLA
      class I-restricted and tumor-specific CTLs recognizing peptide antigens on HLA-A
      alleles of adenocarcinoma or SCC in tumor sites of a substantial number of
      patients with non-small cell lung cancer.

PMID- 9023416
TI  - Down-modulation of CD8 beta-chain in response to an altered peptide ligand
      enables developing thymocytes to escape negative selection.
AB  - Mice expressing a Kb-restricted transgenic T cell receptor (TCR) and a naturally
      occurring MHC class I variant molecule, Kbm8, were used to study thymic
      selection. The transgenic TCR was specific for the major peptide determinant from
      ovalbumin (OVA(257-264)), while Kbm8 has a mutation that alters the position 2
      binding pocket of the Kb molecule, abolishing antigenic peptide presentation and
      positive selection of transgenic T cells. Peptide presentation was restored by
      identifying a position 2 analog peptide with Kbm8-binding capacity. In
      combination with Kbm8, the E2 peptide variant was capable of deleting immature
      double-positive thymocytes in suspension culture. Similarly, addition of
      exogenous E2 peptide to fetal thymic organ culture resulted in efficient deletion
      of double-positive thymocytes. However, there remained a population of CD8 single
      positive T cells that exhibited impaired responsiveness to the antigenic peptide
      and lacked expression of the CD8 beta-chain. These results suggest a mechanism
      whereby developing thymocytes bearing an alphabetaTCR can modify their expression
      of the CD8 coreceptor to escape thymic deletion and achieve self-tolerance.

PMID- 9023417
TI  - Suppression of myelopoiesis and myeloid leukemia cell line proliferation by a
      novel bone marrow-derived factor, reptimed.
AB  - Bone marrow is the major site of hematopoiesis in the adult mammal. Bone marrow
      contains a highly organized microenvironment for the support of hematopoietic
      stem and progenitor cells, including the production of growth factors. Bone
      marrow cells also produce negative regulatory factors which may regulate
      hematopoiesis and inflammatory responses. In this paper we describe Reptimed, a
      unique bone marrow-derived factor with inhibitory activity for myelopoiesis and
      in vitro growth of myeloid cell lines. Reptimed was partially purified from bone
      marrow supernatants using a combination of solid-phase extraction and size
      exclusion chromatography. Reptimed is < 1000 Da MW and is water soluble. Reptimed
      inhibited growth of granulocyte-macrophage and macrophage colonies as well as
      proliferation of several myeloid leukemia cell lines. Reptimed may be part of a
      hemoregulatory circuit.

PMID- 9023418
TI  - Immunoactive products of placenta. VI. Induction of transient murine T cell
      anergy by a low-molecular-weight compound obtained from supernatants of human
      placental cultures.
AB  - A low-molecular-weight material present in human placental supernatant
      (lymphocyte proliferation inhibiting factor, LPIF, or filtrate) can induce
      tolerance/hyporesponsiveness in vivo. We already knew from previous experiments
      that this material acted only on preactivated or malignant T cells, and even the
      malignant cells could be rescued from its action if cells were washed quickly
      after contact. To understand the mechanisms of its action, we have set up systems
      of specific stimulation. The material inhibits anti-Vbeta-specific stimulation.
      In a mixed lymphocyte reaction if responder cell populations from a first MLR
      performed in the presence of LPIF are harvested, extensively washed to discard
      suppressor molecules, and restimulated by related or third-party lymphocytes in
      an H2-incompatible combination, the response to a third-party stimulator (a
      primary one) is unaffected by prior exposure to the material, which nevertheless
      renders the population unresponsive to restimulation by the original MHC
      stimulating haplotype. Cells triggered by anti-Vbeta6 antibodies in the presence
      of LPIF are unable to undergo restimulation by the very same anti-Vbeta6 MoAb,
      while they conserve their capacity to proliferate in a primary fashion in
      response to the unrelated anti-Vbeta8 MoAb. When analyzed by FACS using anti
      Vbeta FITC-conjugated MoAbs, cells that are unresponsive or blocked in their
      proliferation by the action of the filtrate after anti-Vbeta stimulation are
      still live and unexpectedly transiently hyperexpress the TcR. These findings
      confirm the requirement for T cell stimulation for suppression to be enacted and
      demonstrate that such is exerted by anergy rather than by clonal deletion, at
      least in vitro.

PMID- 9023419
TI  - Terminal differentiation of human germinal center B cells in vitro.
AB  - In order to define an in vitro culture system allowing growth of single human
      germinal center B cells (GC-B), we have studied the proliferation and
      differentiation of human tonsillar GC-B, and subsets thereof, when cultured
      together with murine EL-4 thymoma cells in the "EL-4 system." The cells were
      analyzed and compared to resting tonsillar B cells with respect to phenotypic
      changes, proliferation, Ig secretion, intracellular Ig levels, and growth
      abilities under limiting dilution conditions. It was found that GC-B
      differentiated terminally to Ig-secreting cells with the phenotypic features of
      plasma cells in a similar manner to tonsillar resting B cells. The GC-B
      proliferated for 4-5 days, followed by a loss of GC-B phenotype and an increase
      in intracellular immunoglobulin levels. Over a 10-day culture period a larger
      proportion of the Ig produced by GC-B was IgG and IgA, as compared to resting B
      cells, indicating that these cells switched isotype more easily or had already
      switched in the germinal center prior to the culture period. Analysis of
      frequencies of Ig-producing cells revealed that 1/3.8 of GC-B and less than 1/10
      of the centroblast B cell subpopulation (CB-B) differentiated toward Ig-producing
      cells when cultured in the EL-4 system whereas 1/1.25 and 1/1.5 of peripheral
      blood B cells (PBL-B) and resting tonsillar B cells did so, respectively. Taken
      together, these findings show that tonsillar GC-B differentiate in a similar
      manner to resting B cells when cultured in the EL-4 system, and we conclude that
      these conditions allow manipulation of GC-B in single cell cultures in vitro.

PMID- 9023420
TI  - Simultaneous production of T helper-1-like cytokines and cytolytic activity by
      tumor-specific T cells in ovarian and breast cancer.
AB  - Cytotoxic T-cell (CTL) cultures were generated from five ovarian cancer patients
      (OvCTL) and from three breast cancer patients (BrCTL). All CTL lines were T-cell
      receptor (TcR) alphabeta+ and predominantly CD8+ (73 +/- 13%). These CTL lines
      preferentially recognized autologous tumor cells in an HLA class I-restricted,
      and in part HLA-A2-restricted, manner. In addition, the CTL lines recognized
      allogeneic HLA-A2+ ovarian and breast tumor cells. Specific recognition was
      determined by T-cell-mediated cytotoxicity as well as cytokine release. Coculture
      of irradiated autologous tumor cells with OvCTL induced secretion of IFN-gamma,
      GM-CSF and TNF-alpha, but not IL-4, indicating a T helper-1-type response.
      Similar results were obtained when OvCTL and BrCTL were stimulated with
      histologically matched HLA-A2+ tumor cells. Also, BrCTL stimulated with HLA-A2+
      but not HLA-A2- ovarian tumor cells produced significant levels of GM-CSF and TNF
      alpha. Finally, the Her2/neu peptide p654-662, earlier identified as a tumor
      antigen in both ovarian and breast cancer, induced cytotoxicity as well as the
      specific release of IFN-gamma and TNF-alpha but not IL-4 by OvCTL and BrCTL.
      Thus, tumor-specific recognition by CTL was verified by cytotoxicity and cytokine
      release. The secretion of Th1-like cytokines as opposed to Th2-like cytokines
      suggest that therapeutically OvCTL and BrCTL could potentially enhance the
      endogenous immune response to tumor.

PMID- 9023421
TI  - Three cell subsets are required for the transfer of delayed-type hypersensitivity
      reaction by antigen-specific T cell lines.
AB  - Antigen (trinitrochlorobenzene)-specific T cell lines were obtained by repeated
      stimulation of lymph node cells from immune mice with antigen in vitro. These T
      cell lines, consisting of more than 90% CD4+ Vbeta8.2+ and 6 to 9% gammadelta+ T
      lymphocytes, transfer contact sensitivity (CS) locally when injected at the same
      site as the challenge antigen, but fail to mediate a systemic passive transfer
      when injected i.v. Injection of T cell lines together with spleen cells from mice
      immunized 1 day beforehand (1-day cells) allowed a successful, specific systemic
      transfer of CS. Phenotypic analysis showed that the 1-day immune cell was
      alphabeta+, gammadelta-, sIg-, CD3+, CD4-, CD8-, CD5+, B220 (CD45R)+, Thy 1.2+.
      The effect of 1-day immune cells occurred through a mechanism involving IL-4, as
      1-day immune cells failed to allow systemic transfer of CS by T cell lines in
      recipient mice treated with mAb to IL-4. These observations strongly indicate
      that three cell subsets are required for the systemic passive transfer of CS by T
      cell lines: alphabeta+ CD4+, gammadelta+, and a third cell subset, which is
      CD45R+, alphabeta+, CD3+, but double (CD4, CD8) negative.

PMID- 9023423
TI  - Human natural killer cells account for non-MHC class I-restricted cytolysis of
      porcine cells.
AB  - Despite similarities in the cellular response to allografts and xenografts, some
      aspects of the xenogeneic immune response are unique. We find that both freshly
      isolated and primed human peripheral blood lymphocytes manifest MHC unrestricted
      cytolysis of porcine cells. While natural antibody-mediated mechanisms account
      for variable levels of cytotoxicity, reproducible killing in the absence of human
      serum is attributable to natural killer (NK) cells. This was shown by cold target
      inhibition with K562 cells, increased antiporcine cytotoxicity after enrichment
      for CD56+ cells, and significantly reduced lytic activity after depletion of
      CD56+ cells. Increased anti-porcine cytotoxicity after mixed culture of human and
      porcine cells was due to differentiation of NK cells to lymphokine-activated
      killer (LAK) cells and was IL-2 dependent. After depletion of NK cells, T-cell
      mediated anti-porcine cytotoxicity could also be demonstrated. We conclude that
      the human anti-porcine cellular cytotoxic response is due to multiple cell types
      that include T cells in addition to NK and LAK cells.

PMID- 9023422
TI  - Ly1- (CD5-) B cells produce interleukin (IL)-10.
AB  - Interleukin (IL)-10 enhances humoral immunity by inhibiting macrophage activation
      and promoting the development of Th2 cytokine synthesis. In this study we
      investigated the ability of conventional Ly-1- (CD5-) B cells to produce IL-10
      protein. Highly purified normal, naive splenic B cells from both BALB/c and
      C57BL/6 mice produced IL-10 in response to stimulation with the mitogen LPS. In
      addition, B cells from antigen primed mice also produced IL-10 upon antigen
      restimulation in vitro, as analyzed by ELISA and by bioassay. Removal of Ly-1+ B
      cells did not appreciably reduce IL-10 production, indicating that conventional
      Ly-1- B cells produced IL-10. These results indicate that normal Ly-1- B cells
      produce significant quantities of IL-10 during mitogen- or antigen-driven immune
      responses. The production of IL-10 by conventional B cells may enhance their
      capacity to promote humoral immune responses.

PMID- 9023424
TI  - CD72 ligation regulates defective naive newborn B cell responses.
AB  - The biological basis for reduced Ig production by naive newborn B cells compared
      to adult peripheral blood B cells is not fully understood. In a Con A + IL-2 T
      cell-dependent system using "competent" adult T cells, adult B cells produced
      large amounts of IgM, IgG, and IgA, while cord B cells were restricted to low
      levels of only IgM production. Cord B cell activation was also diminished. The
      contribution of specific B-T cell contact-mediated events to the diminished cord
      B cell response in this system, using mAbs to CD40, CD28, CD80, and CD72, were
      investigated, as well as regulation of B cell Ig production by cytokines.
      alphaCD72 ligation increased cord B cell activation and IgM production, but did
      not affect adult B cells. Blocking alphaCD40 mAb inhibited cord B cell Ig
      production completely, but only partly inhibited adult B cell Ig production even
      at high concentration, suggesting a greater sensitivity of cord B cells to
      disruption of the CD40-CD40L interaction. Addition of IL-10 did not increase cord
      B cell Ig production, while adult B cell Ig production was increased. However,
      combined addition of IL-10 and alphaCD72 significantly increased cord B cell Ig
      production over that in the presence of either alphaCD72 or IL-10 alone, but had
      no effect on adult B cells over that of IL-10 alone. These data suggest that the
      diminished T cell-dependent response of cord B cells is due to reduced or absent
      CD72 ligation. CD72 ligation plays an important role in the induction of primary
      responses by naive B cells. CD72 modulation of naive B cell sensitivity to IL-10
      stimulation may have implications in the induction of class switch, which is
      deficient in newborn B cells. Since all T cells express CD5 constitutively, these
      data also suggest the existence of another ligand for CD72.

PMID- 9023426
TI  - N-acetyl-leucinyl-leucinyl-norleucinal inhibits lipopolysaccharide-induced NF
      kappaB activation and prevents TNF and IL-6 synthesis in vivo.
AB  - The effects of N-acetyl-leucinyl-leucinyl-norleucinal (ALLN), a potent inhibitor
      of proteolysis catalyzed by proteasomes, on the activation of NF-kappaB in vitro
      and in vivo have been examined. Confirming earlier observations, ALLN inhibits
      the activation of NF-kappaB in macrophage cultures stimulated with LPS, resulting
      in the intracellular accumulation of IkappaB and p105. The synthesis of TNF, a
      reaction dependent upon NF-kappaB activation, is blocked by ALLN. Treatment of
      mice with LPS results in the induction of TNF and IL-6 within 90 min followed by
      lethal shock at 24 hr. In mice pretreated with ALLN, serum TNF and IL-6 levels
      were significantly lower than those in untreated animals. These studies suggest
      that the proteasome is a novel target for the identification of agents that may
      be useful in the treatment of those diseases whose etiology is dependent on the
      activation of NF-kappaB.

PMID- 9023425
TI  - A shift in the requirement for CD4+ T cells in the generation of AKR/Gross MuLV
      specific CTL in AKR.H-2b:Fv-1b mice occurs prior to the onset of age-dependent
      CTL nonresponsiveness.
AB  - In the current study, the elimination of CD4+ T cells from B6 mice, by treatment
      with anti-CD4 monoclonal antibody, had little effect on their ability to mount an
      AKR/Gross (MuLV)-specific CTL response. In contrast, for AKR.H-2b:Fv-1b mice,
      there was a shift as the mice aged from 5 to 7 weeks to a requirement for CD4+ T
      cells for AKR/Gross MuLV-specific CTL generation. When CD4+ T-cell-depleted AKR.H
      2b:Fv-1b responder mice were immunized at 5 weeks of age they were able to elicit
      a strong anti-AKR/Gross MuLV CTL response. However, if the CD4+ T-cell depletion
      was done at 6 weeks and then the mice were primed in vivo, their antiviral CTL
      responsiveness was markedly decreased. Following CD4+ T-cell depletion at 7 weeks
      the mice were totally incapable of generating anti-AKR/Gross MuLV-specific CTL.
      AKR/Gross MuLV-specific CTL isolated from AKR.H-2b:Fv-1b mice recognized the
      class I-restricted immunodominant epitope (KSPWFTTL) and three subdominant
      epitopes, previously identified as CTL epitopes for B6 mice. Analysis of IL-2,
      IFN-gamma, IL-4, and IL-10 lymphokine profiles in supernates harvested from MLTC
      wells, and the results of supernate transfer experiments, suggested that the age
      dependent shift to CD4+ T-cell dependence in AKR.H-2b:Fv-1b mice does not
      correlate with an obvious change in the in vitro lymphokine profiles. Experiments
      in which exogenous IL-2 was used to supplement in vitro cultures containing CD4+
      T-cell-depleted 7-week responder mice suggested that the CD4+ T-cell requirement
      was at the in vivo priming stage of antiviral CTL generation. These data
      suggested a fundamental change in virus-specific CTL which correlates with slight
      aging in the AKR.H-2b:Fv-1b mouse strain. To our knowledge, this is the first
      report of a shift in the requirement for CD4+ T lymphocytes for the generation of
      virus-specific CTL over such a short period of time. Moreover, it is of interest
      that this shift in CD4+ T-cell-dependence by antiviral CTL occurs just prior to
      the onset of CTL nonresponsiveness in the AKR.H-2b:Fv-1b mouse strain.

PMID- 9023427
TI  - Corpus callosum: sex or size?

PMID- 9023428
TI  - Multiple foci in parietal and frontal cortex activated by rubbing embossed
      grating patterns across fingerpads: a positron emission tomography study in
      humans.
AB  - Somatosensory representations occupy parietal postcentral gyral (S1) and lateral
      sulcal-opercular cortex (S2). To address the issue of possible multiple
      activation foci in these regions and possible differences due to stimulating skin
      directly or through an imposed tool, we studied changes in cerebral blood flow
      with positron emission tomography during passive tactile stimulation of one or
      two fingertips. Restrained fingers were rubbed with embossed gratings using a
      rotating drum stimulator in 11 subjects. For different scans, gratings touched
      the skin directly for optimal stimulation of cutaneous receptors (called skin
      mode stimulation) or indirectly through an imposed guitar plectrum snugly fitted
      to the same fingers (called tool mode stimulation). The latter was expected to
      stimulate deep receptors better. Subjects estimated roughness after each scan.
      Direct skin contact activated statistically validated foci in both hemispheres.
      On the contralateral side these foci occurred in the anterior and posterior limbs
      of the postcentral gyrus and on the ipsilateral side only in the posterior limb.
      Tool mode stimulation activated one contralateral focus that was in the posterior
      limb of the postcentral gyrus. These results suggest at least two maps for distal
      fingertips in S1 with the anterior and posterior foci corresponding,
      respectively, to activations in area 3b and the junction between areas 1 and 2.
      In contralateral S2, skin mode stimulation activated a peak that was anterior and
      medial to a focus associated with tool mode stimulation. The magnitude of PET
      counts contralateral to stimulation was greater in the anterior S1 and the S2
      regions during initial scans but reversed to more activation in the posterior S1
      during later scans. These short-term practice effects suggest changes in neural
      activity with stimulus novelty.

PMID- 9023429
TI  - Structure of the human sensorimotor system. I: Morphology and cytoarchitecture of
      the central sulcus.
AB  - We have studied the morphology of the central sulcus and the cytoarchitecture of
      the primary sensorimotor cortex in 20 human brains obtained at autopsy. Although
      the surface appearance of the central sulcus varies greatly from brain to brain
      (and between hemispheres of individual brains), its deep structure is remarkably
      consistent. The fundus of the central sulcus is divided into medial and lateral
      limbs by a complex junction midway between the sagittal and Sylvian fissures.
      Based on functional imaging studies, this junction appears to be a structural
      hallmark of the sensorimotor representation of the distal upper extremity. We
      also identified and measured area 4 (primary motor cortex) and area 3 (primary
      somatic sensory cortex) in Nissl-stained sections cut orthogonal to the course of
      the central sulcus. Although the positions of the cytoarchitectonic boundaries in
      the paracentral lobule showed considerable interindividual variation, the
      locations of the borders of areas 4 and 3 along the course of the sulcus were
      similar among the 40 hemispheres examined. In addition to describing more
      thoroughly this portion of the human cerebral cortex, these observations provide
      a basis for evaluating lateral symmetry of the human primary sensorimotor cortex.

PMID- 9023430
TI  - Structure of the human sensorimotor system. II: Lateral symmetry.
AB  - We have evaluated the lateral symmetry of the human central sulcus, brainstem and
      spinal cord using quantitative histological and imaging techniques in specimens
      from 67 autopsy cases. Our purpose was to determine whether the preferred use of
      the right hand in the majority of humans is associated with grossly discernible
      asymmetries of the neural centers devoted to the upper extremities. In the
      accompanying report, we described a consistent set of morphological features in
      the depths of the central sulcus that localize the sensorimotor representation of
      the distal upper extremity. Measurements of the cortical surface in this region,
      and indeed throughout the entire central sulcus, showed no average lateral
      asymmetry. Cytoarchitectonic measurements of area 4 and area 3 confirmed this
      similarity between the left and right hemispheres. The medullary pyramids, which
      contain the corticospinal tracts, were also symmetrical, as were the cross
      sectional areas of white and gray matter in the cervical and lumbar enlargements
      of the spinal cord. Finally, we found no lateral difference in the size and
      number of motor neurons in the ventral horns at these levels of the cord. Based
      on these several observations, we conclude that the preferred use of the right
      hand in humans occurs without a gross lateral asymmetry of the primary
      sensorimotor system.

PMID- 9023431
TI  - The relationship between corpus callosum size and forebrain volume.
AB  - Using high-resolution in vivo magnetic resonance morphometry we measured
      forebrain volume (FBV), midsagittal size of the corpus callosum (CC) and four CC
      subareas in 120 young and healthy adults (49 women, 71 men). We found moderate
      linear and quadratic correlations, indicating that the CC and all CC subareas
      increase with FBV both in men and women (multiple r2 ranging from 0.10 to 0.28).
      Allometric equations revealed that these increases were less than proportional to
      FBV (r2 ranging from 0.02 to 0.30). Absolute CC measurements, as well as CC
      subareas relative to total CC or FBV (the latter measures termed the CC ratios),
      were further analyzed with regard to possible effects of handedness, gender, or
      handedness by gender interaction. Contrary to previous reports, left-handers did
      not show larger CC measurements compared to right-handers. The only apparent
      influence of gender was on the CC ratios, which were larger in women. However,
      smaller brains had larger CC ratios which were mainly independent of gender, a
      result of the less than proportional increase of callosal size with FBV. We
      suggest that the previously described gender differences in CC anatomy may be
      better explained by an underlying effect of brain size, with larger brains having
      relatively smaller callosa. This lends empirical support to the hypothesis that
      brain size may be an important factor influencing interhemispheric connectivity
      and lateralization.

PMID- 9023432
TI  - Prenatal development of calbindin D-28K in human visual cortex.
AB  - The distribution of the calcium-binding protein calbindin D-28K (CB) was
      investigated in human fetal primary visual cortex. CB is present in Cajal-Retzius
      cells of layer I, in sparse neurons of the ventricular and intermediate zones
      (VZ, IZ), and in tangential fibres in IZ by 15 weeks (W) of gestation. Cajal
      Retzius cells lose their staining by 30W. CB appears in layers II-VI mainly from
      26W, following an inside-outside sequence. Until 34W, CB labelling is in somata
      and neuropil located primarily in layers IVA, IVC and V. Then reactive perikarya
      and puncta increase in layers II-IVA and deep IVB and C, but are reduced in
      infragranular layers from 34W to term. From 30W positive somata form clusters in
      the cell-rich bands in layers IV and V and labelled neuropil in layers III and IV
      has a periodic pattern from 34W. Also from 34W, numerous lightly reactive
      pyramidal cells are present in layers II to IVA in primary, but not secondary,
      visual cortex. Our results show precocious expression of CB before full laminar
      differentiation of the cortex and that some of this expression is transient.

PMID- 9023433
TI  - Prefrontal deficits in attention and inhibitory control with aging.
AB  - Event-related potentials and behavioral measures were obtained from young and
      elderly subjects while they performed two different auditory delayed match-to
      sample tasks. In each experiment, subjects had to indicate whether an initial and
      a subsequent test sound were identical in two different conditions: one filled
      with distracting tone pips and one with no distractors. Electrophysiologically,
      elderly subjects had reduced attention-related activity over frontal regions. In
      addition, the distracting stimuli elicited an enhanced primary auditory evoked
      response in the elderly. The percentage of perseverative errors on the Wisconsin
      card sorting test, a putative measure of frontal lobe function, was positively
      correlated with the amplitude of the primary auditory evoked response in elderly
      subjects. Behaviorally, elderly subjects were impaired by distractors at long but
      not short delays. Taken together, these results suggest that increased
      distractibility and impaired sustained attention with aging may be due to altered
      prefrontal cortex function. These data support the loss of prefrontal suppression
      over the primary auditory regions with aging.

PMID- 9023434
TI  - Stimulus-dependent modulations of correlated high-frequency oscillations in cat
      visual cortex.
AB  - The hypothesis that correlated neural activity is involved in the cortical
      representation of visual stimuli was examined by recording multi-unit activity
      and local field potentials from neurons with non-overlapping receptive fields in
      areas 17 and 18. Using coherence functions, correlations of oscillatory patterns
      (35-100 Hz) of neural signals were investigated under three stimulus conditions:
      (i) a whole field grating or a long bar moving across both receptive fields; (ii)
      masking the region between both receptive fields while stimulating the remaining
      visual field; and (iii) two separate stimuli simultaneously moving in opposite
      directions. Coherences of oscillations were found to be significantly higher in
      the first stimulus condition than in the other two conditions. Since different
      visual stimuli were reflected in the coherence of neural activity, we concluded
      that correlated neural activity is a potential candidate for coding of sensory
      information.

PMID- 9023435
TI  - Visual pathways for object-oriented action and object recognition: functional
      anatomy with PET.
AB  - The purpose of this study was to identify the functional anatomy of the
      mechanisms involved in visually guided prehension and in object recognition in
      humans. The cerebral blood flow of seven subjects was investigated by positron
      emission tomography. Three conditions were performed using the same set of
      stimuli. In the 'grasping' condition, subjects were instructed to accurately
      grasp the objects. In the 'matching' condition, subjects were requested to
      compare the shape of the presented object with that of the previous one. In the
      'pointing' condition (control), subjects pointed towards the objects. The
      comparison between grasping and pointing showed a regional cerebral blood flow
      (rCBF) increase in the anterior part of the inferior parietal cortex and part of
      the posterior parietal cortex. The comparison between grasping and matching
      showed an rCBF increase in the cerebellum, the left frontal cortex around the
      central sulcus, the mesial frontal cortex and the left inferior parietal cortex.
      Finally, the comparison between matching and pointing showed an rCBF increase in
      the right temporal cortex and the right posterior parietal cortex. Thus object
      oriented action and object recognition activate a common posterior parietal area,
      suggesting that some kind of within-object spatial analysis was processed by this
      area whatever the goal of the task.

PMID- 9023436
TI  - The autonomic-related cortex: pathology in Alzheimer's disease.
AB  - Alzheimer's disease (AD) causes progressive deterioration of cognition and
      behavior. Memory dysfunction is the hallmark, but there are also changes in
      behavior, emotion and autonomic functions, which cannot be explained simply as a
      consequence of memory impairment. These observations suggest that the natural
      disease process of AD involves not only memory-related neural structures, but
      also specific neural systems related to other behaviors, emotion and autonomic
      functions. Since recent evidence has indicated a primary role for ventromedial
      frontal (VMF) cortex in such functions, we examined laminar distribution of
      neurofibrillary tangles and Alz 50 immunoreactive neurons in subdivisions of VMF
      cortex in 20 AD patients and seven age-matched controls. The densities of
      pathological changes were: (i) highest in the posteromedial mesocortical regions,
      particularly Brodmann's area 25 (A25), posterior orbitofrontal cortex (POF) and
      anterior insula (AI); (ii) of comparable severity between posteromedial
      mesocortical regions and most temporal cortices, excluding only the entorhinal
      cortex and temporal pole; and (iii) located predominantly in layer III and
      especially layer V. Further analysis demonstrated selective pathology in layer V
      of A25, POF and AI that would disrupt direct cortico-autonomic projections. This
      is the first study to detail severe AD pathology in these autonomic-related
      cortices, which could contribute to the behavioral changes, emotional disturbance
      and autonomic dysregulation that often accompany AD.

PMID- 9023437
TI  - [Residual activity or defect reversibility on stress-redistribution-reinjection
      201T1 SPECT: which is the better marker of myocardial viability?].
AB  - Although both residual T1 activity and defect reversibility are used as a marker
      of myocardial viability on stress-redistribution-reinjection T1 (T1-RI) imaging,
      it is not yet fully understood which marker better predicts reversible
      dysfunction after revascularization. The aim of this study was to assess the
      comparative efficacies of these criteria for prediction of functional recovery
      after revascularization. Twenty-five patients (LVEF 41%) who underwent successful
      revascularization were studied with T1-RI SPECT and gated blood pool scintigraphy
      before revascularization. The gated blood pool study was repeated at mean 2
      months after revascularization. The left ventricular myocardium was divided into
      9 segments and the mean regional activities were calculated for each segment. In
      this study, two independent criteria were used as a viability index; (A) the
      presence of residual T1 activity (> 50% of peak) on the final image (reinjection
      image), (B) reversible defect (> 10% increase on the subsequent images) or normal
      T1 uptake (> 80% of peak) on the initial image. Functional recovery occurred in
      51 of 88 dysfunctional segments. The presence of residual T1 activity was a
      highly sensitive (96%) but poorly specific (35%) marker of reversible
      dysfunction, while a reversible defect or normal T1 uptake was a less sensitive
      (67%) but more specific (59%) predictor of functional recovery. In conclusion,
      defect reversibility provides unique information on myocardial viability which
      cannot be obtained by assessing residual T1 activity alone.

PMID- 9023438
TI  - [An improved automated synthesis and in vivo evaluation of PET radioligand for
      serotonin re-uptake sites: [11C]McN5652X].
AB  - Carbon-11 labeled serotonin (5-HT) re-uptake inhibitor, [11C]McN5652X [(6S, 10bR)
      trans-(+)-1,2,3,5,6,10b-hexahydro-6-[4-(methylthio)phenyl] pyrrolo-[2,1-a]
      isoquinoline], has recently been reported to be favorable for studying human 5-HT
      re-uptake site by positron emission tomography (PET) because of its rapid and
      high specific binding characteristics as radioligands. [11C]McN5652X has been
      synthesized by S-methylation of the corresponding des-methyl precursor A with
      [11Cliodemthane. One serious disadvantage of this procedure, however, is the lack
      of stability of A. The improved method for the synthesis of A has been desired.
      We have found that the decomposition of A is significantly reduced by adding a
      protecting agent for SH groups, dithiothreitol (DTT), into the reaction medium
      immediately after the demethylation of McN5652X. By using this stabilized
      precursor A, we have developed an automated procedure giving [11C]McN5652X with
      98.6 +/- 0.4% radiochemical purity in high specific activity (181.3 +/- 7.4
      GBq/mumol). Preclinical evaluation of the product was carried out by injecting
      the solution of [11C]-McN5652X obtained by this procedure into mice.
      [11C]McN5652X showed the high accumulation into mouse thalamus, striatum and
      cerebral cortex, organs known to have high level of 5-HT receptor density, after
      intravenous injection. Human PET studies also showed the high uptakes of this
      radioligand into the thalamus, striatum and midbrain.

PMID- 9023439
TI  - [The serial change of the 123I-BMIPP SPECT in patients with hypertrophic
      cardiomyopathy].
AB  - We studied the serial change of 123I-BMIPP SPECT in the process of hypertrophic
      cardiomyopathy (HCM). In 16 patients with HCM, the imaging data were acquired 15
      minutes after injection of 111 MBq 123I-BMIPP. The SPECT image was divided into
      17 segments and the severity of the defect in each segment was scored visually
      using defect score, a 4-point grading system (score 0 = normal, score 1 = mildly
      decreased uptake, score 2 = moderately decreased uptake, score 3 = severely
      decreased uptake or defect). Each patient underwent this examination twice with
      interval of 25 +/- 14 months. In the first examination, we observed reduced
      uptake in 14 cases (88%), and often found it in septal portion of anterior or
      posterior wall. In the second examination, compared with the first study, total
      defect score (TDS: the summation of defect score of 17 segments) had increased in
      7 cases (44%) of 16 cases, decreased in only 1 case (6%), and unchanged in 8
      cases (50%). The regional defect score often increased in septal portion of
      anterior and posterior walls, and the high score area widespread toward the
      septum. There was no difference between TDS unchanged group and TDS worsened
      group in the point of background (age, family history of HCM), the interval of
      the two studies, and the findings of echocardiography (Dd, Ds, %F). In TDS
      worsened group (n = 7), clinically only 1 case became progressed stage. In others
      there were no progression in each clinical, echocardiographic, or 201Tl
      scintigraphic findings. This study revealed that myocardial fatty acid metabolic
      disorder often progresses during short interval in patients with HCM. In
      conclusion, the serial examination of 123I-BMIPP SPECT may contribute to an
      estimation of the stage or the prognosis in HCM.

PMID- 9023440
TI  - [A case of bilateral adrenal neuroblastomas detected by bone scintigraphy].
AB  - A 7-month-old girl, who had been resected the left adrenal neuroblastoma 20 days
      ago, underwent bone scintigraphy with 90mTc-HMDP to survey bone metastases. The
      bone scan demonstrated avid uptake in the right adrenal gland, in which 123I-MIBG
      also accumulated. However, the degree of 123-I-MIBG uptake in the right adrenal
      gland was not necessary higher compared to that in the normal adrenal glands in 7
      patients after resection of hemilateral neuroblastomas. Reviewing the
      preoperative abdominal CT, a swelling of the right adrenal gland had been
      overlooked because of the small size of 10 x 12 mm in diameter. The follow-up CT
      after surgery revealed a more growth of the right adrenal gland, accompanied by
      reelevation of urine vanilmandelic acid. This patient was thus diagnosed as
      bilateral neuroblastomas. Because bone scintigraphy frequently shows abnormal
      uptake in primary neuroblastomas, it has potentially diagnostic value for early
      detection of bilateral adrenal neuroblastomas.

PMID- 9023441
TI  - [A case of transient tic disorder with abnormal findings on 99mTc-HMPAO SPECT].
AB  - We report a case of transient tic disorder with abnormal findings on 99mTc-HMPAO
      SPECT. The patient was 5-year-old girl with vocal and motor tic. There was no
      evidence of structural abnormality on magnetic resonance imaging (MRI).
      Electroencephalogram (EEG) showed spikes and sharp waves on both frontal lobes
      and parietal lobes (left-side dominant). 99mTc-HMPAO SPECT demonstrated focal
      regions of hyperperfusion in the both frontal lobes, both parietal lobes and
      right temporal lobe corresponding to the abnormal findings detected by EEG. It
      also demonstrated an area of hyperperfusion in the right basal ganglia. It is
      suggested that 99mTc-HMPAO SPECT is useful for the diagnosis and the
      understanding of the clinical state of tic disorder.

PMID- 9023442
TI  - [Effectiveness of the radioactive strontium (89Sr) chloride agent, SMS.2P for
      pain palliation in patients with metastatic bone tumor in phase III multicenter
      clinical trial].
AB  - The phase III clinical trial of strontium-89 chloride agent (SMS.2P) was
      performed in 90 patients with painful bone metastases secondary to prostate (53),
      breast (18) and other types of cancer (19). Some patients experienced a transient
      increase in pain or nausea and vomiting. However both symptoms subsided and
      serious side effects were not observed in any of the patients. As reported, we
      confirmed some abnormal changes in peripheral blood picture. A decrease in the
      number of white blood cells and platelets was considered to be partly a result of
      bone marrow suppression due to 89Sr irradiation. Pain was substantially improved
      after 89Sr therapy in 58% of the patients and there was some alleviation in 12%.
      The release from pain was accompanied by an improved quality of life for these
      patients including sleep patterns and morbidity. Some patients were able to
      resume their former life styles. Most of the improved patients experienced pain
      relief from days to one week following 89Sr therapy and in half cases, this
      remained effective for 2 or 3 months. There were even cases in which the pain
      relief continued over an observation period of time of clinical study.

PMID- 9023443
TI  - [Development of a new statistical evaluation method for brain SPECT images].
AB  - The purpose of this study was to develop a new statistical evaluation method for
      Brain SPECT images. First, we made normal brain image databases using 99mTc-ECD
      and SPECT in 10 normal subjects as described previously. Each SPECT images were
      globally normalized and anatomically standardized to the standard brain shape
      using Human Brain Atlas (HBA) of Roland et al. and each subject's X-CT. Then,
      mean and SD images were calculated voxel by voxel. For the next step, 99mTc-ECD
      SPECT images of a patient were obtained, and global normalizing and anatomical
      standardization were performed as the same way. Then, a statistical map was
      calculated as following voxel by voxel; (P-Mean)/SD x 10 + 50, where P, Mean and
      SD indicate voxel value of patient, mean and SD images of normal databases,
      respectively. We found this statistical map was helpful for clinical diagnosis of
      brain SPECT studies.

PMID- 9023444
TI  - [Basic study of continuous repetitive data acquisition using a phantom].
AB  - We evaluated the appropriate rotation rate in the continuous reverse collection
      mode of single photon emission computed tomography (SPECT), in phantoms and in
      volunteers. Since a SPECT examination generally takes 15 minutes, the rotation
      rate was changed from 1, to 3, 6, 9 and 12/15 minutes. A lower rotation rate
      resulted in clearer visualization of the lattice and less variance of data in
      each collection direction in a columnar phantom, and higher image homogeneity and
      clearer visualization of the defective area in a myocardial phantom. There was a
      correlation represented by regression equation y = 0.0243x2 - 0.7843x + 98.136 r2
      = 0.9802 between the rotation rate and variance of data in each collection
      direction. There was also a correlation represented by the regression equation y
      = -0.0034x2 + 0.0157 + 1.2394 r2 = 0.9943 between the rotation rate and the total
      count corrected with that obtained in the step mode (conventional collection).
      Better 99mTc-1,2-bis[bis(2-ethoxyethyl) phosphino]ethane (Tetrofosmin) myocardial
      scintigraphy images were obtained at a lower rotation rate in a normal volunteer.
      In conclusion, a rotation rate of 3-6/15 minutes may be appropriate in continuous
      reverse collection.

PMID- 9023445
TI  - Social factors leading to juvenile delinquency.
AB  - According to the White Paper on Crime 1994 published by the Ministry of Justice
      in Japan, the delinquent rate in Japan was highest when juveniles were
      approximately 14 to 16 years old, and declined as they grew older. The analysis
      of juvenile offenders in Japan showed that 70% of them had two living parents,
      90% of them from families which were financially stable or affluent. The
      breakdown of their parents attitudes showed, however, that 48.2% were classified
      as neglectful, followed by harshness at 30.3% and spoiling or overprotection at
      17.3% in 1993 in Japan. In the following, social factors leading to juvenile
      delinquency were reviewed. Factors leading to juvenile delinquency were
      classified into social factors, school factors and home factors, and recent
      findings concerning those three factors were explained. A fairly clear outlook on
      the efforts required by society, schools and families to reduce juvenile
      delinquency was shown by revealing important factors leading juveniles to
      delinquency.

PMID- 9023446
TI  - Advances and usefulness of ultra-thin bronchofiberscopes.
AB  - We developed new types of ultra-thin bronchofiberscopes, BF-2.2T and BF-2.7T to
      observe and photograph lesions of 2 mm or less in bronchioli. BF-2.2T and BF-2.7T
      can be bent to achieve a vertical range of 120 degrees. BF-2.7T has an additional
      channel for biopsy and can be used to collect cells. The ultra-thin
      bronchofiberscopes allowed us to observe all cases of peripheral pulmonary
      carcinoma and to collect cells. We are now studying IL-6, IL-8 and mRNA in cell
      specimens collected from patients with lung cancer using the ultra-thin
      bronchofiberscopes. The development of the ultra-thin bronchofiberscopes have
      allowed remarkable advances in clinical practice and research because these
      endoscoped allow bronchioles to be observed directly and to collect bronchial
      epithelial cells from necessary areas for subsequent incubation and cytological
      assessment.

PMID- 9023447
TI  - Vibrating probes: new technology for investigation of endolymph homeostasis.
AB  - It is well known that the function of the cochlear and vestibular labyrinth
      depends on the high concentration of potassium (K+) in the luminal fluid,
      endolymph. Homeostasis of endolymphatic ion composition has been attributed to
      the stria vascularis and vestibular dark cells but with little prior experimental
      basis. The extremely small domain of each epithelial cell type bounding the
      endolymphatic space has precluded study of ion fluxes from these cells. The
      voltage-sensitive and (+)-selective vibrating probes were adapted recently for
      the demonstration of electrogenic K+ secretion and its regulation by stria
      vascularis and vestibular dark cell epithelium. The isolated stria vascularis and
      vestibular dark cell epithelium are known to produce a transepithelial current
      directed toward the endolymphatic side and this current has been shown to be
      sensitive to bumetanide, an inhibitor of the Na(+)-Cl(-)-K+ cotransporter. The
      vibrating probes were used to demonstrate that this current is carried by K+ and
      that the K+ flux is also sensitive to bumetanide. Several other agents and
      maneuvers which alter the transepithelial current (e.g. apical DIDS and
      basolateral hypotonic challenge) were found to produce similar changes in the K+
      flux. The technique holds the promise of discovery of the contribution to the
      homeostasis of endolymph of other cell types in the inner ear.

PMID- 9023448
TI  - Pathology of acquired immunodeficiency syndrome (AIDS) in children.
AB  - OVERVIEW: Acquired Immunodeficiency Syndrome (AIDS) was first described to occur
      in children in 1983. With experience of increasing number of cases of AIDS,
      pathologic lesions in various organs and tissues such as lungs, brain, G.I.
      tract, heart, blood vessels, lymph nodes, spleen, bone marrow, etc. became
      evident in autopsy and biopsy specimens. These pathologic lesions were classified
      into four groups based on known or suspected pathogenesis: 1) Primary lesions due
      to Human Immunodeficiency (HIV) infection itself (lymph nodes, brain, etc) 2)
      associated lesions related to direct or indirect sequelae of HIV infection
      (Opportunistic infections, PLH/LIP complex, etc) 3) lesions of undetermined
      pathogenesis, (cardiomyopathy, arteriopathy, thrombocytopenia, nephropathy, etc)
      4) lesions of multifactorial pathogenesis (villous atrophy of intestine, thymic
      lesions, etc). UPDATE: In recent years the emphasis of pathologic study is on the
      reactive and neoplastic proliferative disorders. These disorders include nodal
      and extranodal lymphoproliferative lesions (such as myoepithelial sialadenitis,
      malignant lymphomas, etc), smooth muscle tumors (SMTs), Kaposi's sarcoma, Human
      Papilloma virus associated genital lesions and miscellaneous tumors. In a recent
      study, it has been shown that Epstein-Barr virus (EBV) may be related to the
      pathogenesis of SMTs. The most recently recognized lymphoproliferative lesions
      include those of mucosa associated lymphoid tissue (MALT) of salivary glands,
      lungs and tonsils. The MALT lymphomas in children with AIDS are responsive to
      therapy and tend to take an indolent clinical course. Therefore recognition of
      MALT lymphomas as a distinctive lesion in pediatric AIDS is of practical
      importance. In this view of increasing incidence of HIV and HPV infections in
      adolescent females seen in certain countries attention should also be focused on
      early detection of HPV related genital lesions so that their possible progression
      to intraepithelial and invasive cervical carcinoma can be prevented.

PMID- 9023449
TI  - Ventricular arrhythmias and sudden cardiac death: an insight from recent
      multicenter randomized clinical trials.
AB  - While post-myocardial infarct patients with frequent ventricular premature
      contractions or nonsustained ventricular tachycardia (NSVT) are at an increased
      risk of sudden arrhythmic death, the empirical use of antiarrhythmic agents for
      such patients is no longer justified after the results of the Cardiac Arrhythmia
      Suppression Trial. A series of major breakthroughs in the design and clinical
      application of the implantable cardioverter defibrillator (ICD) have taken place
      over the past two decades since its invention by M Mirowski. Although there is a
      general consensus for the effectiveness of the ICD therapy in aborting sudden
      arrhythmic death, it is unknown whether the use of the ICD therapy results in
      prolonged survival. Three randomized clinical trials directed to the survivors of
      cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation
      (VF) are currently in progress, comparing the ICD therapy with drug therapy
      (amiodarone, beta blockers, and sotalol). Already over seventeen hundred patients
      have been randomized and followed in these three clinical trials. All three
      trials continue currently indicating no emergence of statistically significant
      differences in total mortality between the two therapy groups. Prophylactic
      application of the ICD has been studied in the MADIT (Multicenter Automatic
      Defibrillator Implantation Trial)--the first randomized clinical trial dealing
      with implantable defibrillators. This study enrolled post-transmural infarct
      patients having documented NSVT, left ventricular dysfunction (ejection fraction
      35% or lower) and inducible and nonsuppressible NSVT. The study was recently
      terminated because of an emergence of a highly significant lower mortality with
      the ICD therapy than with conventional drug therapy. The future for patients at
      an increased risk of sudden cardiac death is much brighter with future refinement
      of the ICD system and antiarrhythmic drug therapy, and with further improvement
      in the therapy directed at the underlying structural heart disease.

PMID- 9023450
TI  - The ultrastructural localization of NADPH-diaphorase in the cerebral arteries of
      rats.
AB  - The ultrastructural localization of nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d), which has been considered to be a neuronal nitric oxide
      synthase (NOS), was explored in the vascular endothelial cells and perivascular
      nerves of the cerebral arteries in the rat. In order to detect NADPH-d activity,
      2-(2'-benzothiazolyl)-5-styryl-3-4-(4'-phthalhydrazidyl) tetrazolium chloride was
      utilized as a substrate for NADPH-d histochemistry at the electron microscopic
      level. In vascular endothelial cells, NADPH-d positive deposits were observed on
      the nuclear envelope and the endoplasmic reticulum (smooth or rough surfaced).
      Positive deposits were seen on distinct membrane portions of the endoplasmic
      recticulum (ER) in the perivascular nerves (axons), but no positive materials
      were observed either in the cytoplasm of the endothelial cells or in the axoplasm
      of the perivascular nerves. It was concluded that NOS is located on the membranes
      of the ER and the nuclear envelope, and that NOS may play substantial roles in
      the regulation of the cerebral vessels.

PMID- 9023451
TI  - Comparative study of epidurally administered clonidine and buprenorphine on
      anesthetic requirement and electroencephalographic activity.
AB  - The author investigated the effects of epidurally administered buprenorphine
      (BPN) and clonidine (CLO) on the potentiation of halothane anesthesia in terms of
      the minimum alveolar concentration (MAC), hemodynamics, and
      electroencephalographic activity in the patients undergoing lower abdominal
      surgery. Thirty-four women (ASA-1) were studied after the epidural administration
      of either 10 ml saline (group A, n = 8), 10 ml saline with 0.4 mg BPN (group B, n
      = 13), or 10 ml saline with 150 micrograms CLO (group C, n = 13). The MAC of
      halothane was reduced by 32% in group B (p < 0.05), and by 23% in group C (p <
      0.05) compared with group A. The delta activity on the electroencephalogram (EEG)
      was more dominant in groups B and C 20 and 30 minutes after the administration of
      BPN and CLO compared with group A. The alpha activity in group A was
      significantly greater than that in the other groups. The delta activity in groups
      B and C was increased significantly compared with group A. The blood pressure was
      significantly lower after the epidural administered of CLO in group C, compared
      with groups A and B. The study concluded that epidurally administered CLO
      significantly reduce the MAC of halothane and also resulted in significant
      acceleration of delta activity on the EEG, as did BPN. The mechanisms by which
      the central nervous system (CNS) is depressed by epidural BPN and CLO are
      different, but this may have resulted from their direct action on the CNS via the
      systemic and spinal absorption of BPN and CLO.

PMID- 9023452
TI  - Laparoscopic presacral neurectomy utilizing contact-tip Nd: YAG laser.
AB  - The performance of the presacral neurectomy with a standard laparoscopic approach
      utilizing a Contact-tip Nd: YAG Laser with the GRP6 sapphire scalpel tip is
      feasible, effective, and safe. Patients suffering from severe disabling
      dysmenorrhea have had complete relief of their symptoms with up to an eighteen
      month follow up. The resection of the presacral nerve plexus is associated with
      significant relief of symptoms. The pain impulses from the uterus which travel
      through the inferior hypogastric plexus into the intermediate hypogastric plexus
      and the superior hypogastric plexus can be interrupted by the performance of this
      procedure in a laparoscopic manner. The intermediate hypogastric plexus which is
      composed of two or three trunks lying on the vertebral body of L5 is the most
      appropriate place for the resection. The presacral neurectomy is not appropriate
      treatment for relief of lateral or back pain. Patients with midline pain will
      experience significant relief by the use of this procedure. In conclusion, the
      performance of the presacral neurectomy utilizing the Contact-tip Nd: YAG Laser
      with GRP6 sapphire tip combined with other conservative surgery for resection of
      endometriosis does offer relief of dysmenorrhea and other pelvic pain and is an
      alternative for women wishing further childbearing and those who do not wish a
      hysterectomy. Twenty women in whom this procedure has been performed have
      reported a decrease in pain level from 9.4 (scale of 0 = no pain to 10 =
      disabling pain) to 2.0 with follow up to 18 months. There have been no
      complications with this procedure.

PMID- 9023453
TI  - Minimally differentiated acute myeloid leukemia, AML-M0, terminated in candidial
      fungemia.

PMID- 9023454
TI  - Synthetic lipid A produces antitumor effect in a hamster pancreatic carcinoma
      model through production of tumor necrosis factor from activated macrophages.
AB  - The antitumor effect and biological activities of a newly synthesized lipid A
      analogue (ONO-4007) were investigated in a hamster pancreatic carcinoma model.
      Marked and dose-dependent inhibition of tumor growth was achieved by i.p.
      injection twice a week for 3 weeks of 10, 30 or 50 mg/kg of ONO-4007. Endogenous
      tumor necrosis factor (TNF) activities induced by ONO-4007 were significantly
      greater in tumor than in serum, spleen and liver. TNF production by macrophages
      stimulated with ONO-4007 after culture was much greater when culture was
      performed in the presence of hamster pancreatic carcinoma cells (no cell-to-cell
      contact). It was further found that the cytotoxic activity of TNF secreted by
      macrophages cultured with cancer cells was inhibited in the presence of anti-TNF
      neutralizing antibodies. These findings suggest that ONO-4007 displays antitumor
      effects by stimulating production of endogenous TNF in tumor macrophages,
      possibly through activation by soluble macrophage-stimulating factors in cancer
      cells.

PMID- 9023455
TI  - Antibody mediated ligation of platelet/endothelial cell adhesion molecule-1
      (PECAM-1) on neutrophils enhances adhesion to cultured human dermal microvascular
      endothelial cells.
AB  - We investigated the effects on leukocyte adhesion to cultured human dermal
      microvascular endothelial (DMvE) cell by antibody mediated ligation of
      platelet/endothelial cell adhesion molecule-1 (PECAM-1) on neutrophils.
      Preincubation of neutrophils with anti-PECAM-1 antibody markedly enhanced their
      adhesion to DMvE cells, while the adhesion-increasing action was cancelled out by
      anti-CR3 or anti-LFA-1 beta (CD18) antibody. These findings suggest that ligation
      of PECAM-1 on neutrophils increases their adhesion to cultured DMvE cells
      depending on the beta 2 integrin family, and PECAM-1 may have a crucial role in
      dermal inflammation.

PMID- 9023456
TI  - Tyrosine phosphorylation of protein kinase C delta-isoform and its association
      with membrane.
AB  - Stimulation of CHO cells stably overexpressing the delta-isoform of protein
      kinase C (delta PKC) by phorbol ester resulted in the tyrosine phosphorylation
      and association of the enzyme with particulate fraction. This tyrosine
      phosphorylation of delta PKC occurred preferentially in the enzyme
      prephosphorylated at serine/threonine residue(s). The enzymatic activity of
      tyrosine-phosphorylated delta PKC was dependent on both phospholipid and
      diacylglycerol which is the same as the non-tyrosine-phosphorylated form, and no
      significant difference was observed between the two forms for their kinetic
      properties and specific activities. When delta PKC was phosphorylated at tyrosine
      in vitro, phosphatidylserine and either diacylglycerol or phorbol ester were
      needed for the maximal rate of the reaction, suggesting that the tyrosine
      phosphorylation is a consequence of, but not a prerequisite for the enzyme
      activation. The tyrosine-phosphorylated delta PKC was associated with the
      particulate fraction, and presumably exists as a large complex in the membrane of
      the stimulated cells. It may be possible that the tyrosine phosphorylation is
      related to sustained activation and/or targeting of the delta PKC isoform.

PMID- 9023457
TI  - Non clamping anastomosis of the ascending and arch aneurysm using retrograde
      cerebral perfusion.
AB  - Twelve consecutive patients requiring surgery for replacement of ascending aortic
      aneurysms (n = 3), ascending arch aortic aneurysms (n = 2), or type A aortic
      dissections (n = 7) were treated without aortic cross clamping. Retrograde
      cerebral perfusion (RCP) with circulatory arrest (mean RCP time: 46.0 +/- 15.9
      minutes, range 20 to 65 minutes) and continuous retrograde cardioplegia (mean
      cardiac ischemic time: 134.4 +/- 39.7 minutes, range: 40 to 180 minutes) were
      employed. In the patients with aortic dissection, the intimal tear at the origin
      of the brachiocephalic artery (BCA) was resected completely, the aortic wall was
      trimmed and closed with Teflon felt. The distal anastomosis was created using an
      open technique. Air and debris were completely evacuated by returning blood from
      the cerebral vessels and femoral artery. Then the artificial graft was clamped,
      and cardiopulmonary bypass resumed. The proximal anastomosis was performed during
      rewarming. The operations were elective in seven cases, and emergent in five
      cases. Graft replacement of the ascending aorta was performed in ten patients
      (including two BCA reconstructions). The remaining two patients were treated by
      patch repair (n = 1), primary anastomosis (n = 1). There were no perioperative
      deaths. One patient had a transient neurological deficit. The distal false lumen
      was occluded completely in five of seven patients with aortic dissections. The
      other two patients had a secondary tears in the descending aorta. Thus retrograde
      cerebral perfusion and continuous retrograde cardioplegia without aortic cross
      clamping is an effective technique in the replacement of the ascending and arch
      aorta.

PMID- 9023458
TI  - Factors affecting appearance patterns of hip-flexion contractures and their
      effects on postural and gait abnormalities.
AB  - Hip flexion contractures accompanying various orthopedic and neurologic
      conditions not only limits the physical activities of the patients but also
      distorts their postures and gait patterns. The purposes of this study were to
      characterize the appearance patterns of flexion contracture at the hip joints and
      to elucidate how this disability affects their postural and gait abnormalities.
      Seventy-eight patients (mean age of 68.1 +/- 10.5 years) with hemiplegia, femoral
      neck fractures, osteoarthritis of the hip and other conditions causing hip
      flexion contractures were studied. The presence and degree of hip flexion
      contracture were estimated in the supine position using the Thomas maneuver with
      a goniometer. Relationship between appearance patterns and 12-survey variables
      was also analyzed statistically. As a result, it was revealed that whether lack
      of mobility caused by hip flexion contracture was compensated for by pelvic tilt
      an an increase of lumbar lordosis or not was affected by four factors. It was
      also revealed that whether it appeared unilaterally or bilaterally was affected
      by five factors. In addition, some postural and gait abnormalities caused by hip
      flexion contracture were observed in many patients. These results suggest that
      clinical pictures of the patient's posture and gait abnormality depend on his
      ability to regulate the position of the trunk and knees as well as the mobility
      of his spine.

PMID- 9023459
TI  - Inulin and oligofructose do not influence the absorption of cholesterol, or the
      excretion of cholesterol, Ca, Mg, Zn, Fe, or bile acids but increases energy
      excretion in ileostomy subjects.
AB  - OBJECTIVE: To investigate the effects of inulin and oligofructose on cholesterol
      absorption and excretion of cholesterol, bile acids, energy, nitrogen and
      minerals in man. DESIGN: Double-blind cross-over study. SETTING: Metabolic
      kitchen with policlinic visits, Sahlgrenska Hospital, Goteborg, Sweden. SUBJECTS:
      Patients with conventional ileostomy because of ulcerative colitis.
      INTERVENTIONS: 7 g of inulin, 17 g of oligofructose and 7 g of sucrose were added
      to a controlled diet during three experimental periods of three days each.
      Ileostomy effluents were collected and analysed. Differences between experimental
      and control diet were investigated with the Wilcoxon's sign and values test.
      RESULTS: Inulin and oligofructose were recovered in the ileostomy effluent to 88%
      (95% CI, 76-100%) and 89% (64-114%) respectively. Dry solid excretion increased
      by 14.4 g (11.3-17.5) on inulin, and by 14.7 g (13.0-16.4 g) on oligofructose and
      energy excretion increased 245 kJ (190-307 kJ) on inulin and 230 kJ (214-315 kJ)
      on oligofructose compared to control diet (P < 0.05). Cholesterol absorption,
      excretion of cholesterol, bile acids, nitrogen, fat, calcium, magnesium, zinc and
      iron were not affected by inulin and oligofructose. CONCLUSIONS: Inulin and
      oligofructose are not digested in the small intestine. They do not affect mineral
      excretion and hence hardly mineral absorption. They do not increase fat or
      nitrogen excretion from the small intestine. Any physiological effect of inulin
      and oligofructose is probably mediated through other mechanisms than altered
      excretion from the small intestine.

PMID- 9023460
TI  - Body mass index reference curves for children aged 3-19 years from Verona, Italy.
AB  - OBJECTIVE: To compile curves for Body Mass Index (BMI) for Italian children and
      adolescents. DESIGN: Cross sectional study. SETTING: All primary and secondary
      schools of Verona, Italy between October 1986 and January 1987. SUBJECTS: 20,796
      males and 21,073 females children, aged 3-19 y. METHODS: Weight and height were
      measured using Salus balances, and age in days was calculated between the date of
      measurement and that of birth: centiles of BMI by age were calculated by the LMS
      method of Cole (1990). RESULTS: The centiles obtained were similar to those
      obtained in UK by Cole et al, 1995. Compared to Cachera's data for France and
      Hammer's for USA, our BMI values are higher, though closer to the American than
      the French ones.

PMID- 9023461
TI  - Evaluation of oro-coecal transit time: a comparison of the lactose-[13C,
      15N]ureide 13CO2- and the lactulose H2-breath test in humans.
AB  - OBJECTIVE: The lactulose H2-breath test is the most widely used non-invasive
      approach for evaluation of orocoecal transit time (OCTT). In the present study,
      doubly-labelled lactose-[13C, 15N]ureide (DLLU) was synthesized to investigate
      the OCTT in comparison to the conventional lactulose H2-breath test. Additionally
      the bacterial breakdown rate (BBR) and rate of elimination and the metabolic
      pathways of the cleavage products of DLLU (13CO2, [15N]urea, and 15NH3) were
      investigated. DESIGN AND SUBJECTS: In a first study, DLLU was administered as a
      single oral-pulse-labelling (dosage: one gram) either without and after
      pretreatment of five grams of unlabelled lactoseureide (LU) on the day prior to
      the study to twelve healthy adult volunteers after breakfast. Breath and urine
      were collected in one and two hour-intervals, respectively, over a one-day
      period. 13C-enrichment in breath as well as 15N-enrichment in urine fractions
      were measured by continuous flow-isotope ratio mass spectrometry (CF-IRMS). In a
      second study, lactulose was administered to the same subjects (dosage: ten
      grams). Breath was collected in quarter, half and one hour-intervals over a ten
      hour-period. Hydrogen concentration in breath was analysed using an
      electrochemical detector. RESULTS: The comparison of the lactose-[13C]ureide
      13CO2-breath test and the lactulose H2-breath test showed that the mean increase
      of the 13C-enrichment in CO2 occurred 1.18 h later than the mean increase of H2
      in breath. The resulting OCTTs derived from the two methods were 3.02 +/- 1.4 and
      1.84 +/- 0.5 h (P < 0.05) and the corresponding BRs were 9.63 +/- 3.4 and 6.07 +/
      1.7 h (P < 0.01), respectively. The 15N-enrichment of urinary urea and ammonia
      without and after pretreatment with LU started between two and three hours after
      DLLU-administration. The cumulative percentage urinary excretion of the 15N- and
      13C-tracer was 29.9% and 13.6% respectively, and was slightly increased after LU
      pretreatment to 32.1% and 14.6% of the dose administered. A total of 35.2% of the
      13C was found to be exhaled and remained approximately constant after LU
      pretreatment (36.2%). CONCLUSIONS: The use of the lactulose H2-breath test for
      evaluation of the OCTT showed a statistically significant shortening of 1.18 h in
      comparison to the lactose-[13C]ureide 13CO2-breath test in healthy adults. The
      most important limitations of the lactulose H2-breath test are its low
      specificity and sensitivity due to dose-dependent accelerations of OCTT,
      interfering H2-rise from malabsorbed dietary fibre and H2-non-producers. In
      contrast, our lactose-[13C]ureide 13CO2-breath test was confirmed to avoid these
      disadvantages and to yield reliable results. This test is recommended especially
      if higher sensitivity and specificity is required, if IRMS-technique is available
      and if lactulose H2-tests lead to insufficient results.

PMID- 9023462
TI  - A longitudinal study of the growth of matched pairs of vegetarian and omnivorous
      children, aged 7-11 years, in the north-west of England.
AB  - OBJECTIVE: To assess the ability of a meat free diet to support normal growth of
      children. DESIGN: A one year longitudinal observational case--comparison study of
      growth. SETTING: Children were recruited mainly through schools from Merseyside
      and all measurements were taken in their homes. SUBJECTS: Fifty 'free-living'
      children following meat free diets, aged 7-11 y (expected to be pre-pubertal),
      were compared with a control group of 50 omnivores matched for age, sex and
      ethnic group. INTERVENTION: None. MAIN OUTCOME MEASURES: Height, weight, upper
      arm skinfold thicknesses and mid-upper arm circumference measurements were taken
      at baseline and one year later. The increments over one year were each analysed
      using a multiple stepwise regression model which derived predicted increments
      controlled for a variety of factors other than the diet factor. RESULTS: Of all
      the anthropometric measurements examined only the predicted height increment of
      the vegetarians was slightly greater than that of the omnivores (difference in
      predicted height increment = 0.47 cm, P = 0.05). This difference was only
      apparent after allowing for father's height, maternal smoking habit and number of
      siblings. A tendency for the vegetarians to be leaner than the omnivores was not
      significant at the 5% level and both the vegetarian and omnivorous groups lay
      close to the 50th percentiles for both height and weight (Child Growth
      Foundation, 1994). CONCLUSIONS: The results suggest that these children who
      followed a meat free diet and conventional lifestyles grew at least as well as
      children who ate meat.

PMID- 9023463
TI  - The impact of vitamin A supplementation on physical growth of children is
      dependent on season.
AB  - OBJECTIVE: To determine the impact of vitamin A supplementation on physical
      growth in young children. DESIGN: Randomized, double blind, placebo controlled
      trial. SETTING: Urban slum community clinic. SUBJECTS: 900 children, aged 12-59
      months, attending the community clinic with diarrhea of < or = 7 d were included
      in the trial. INTERVENTION: Each child was given a single dose capsule containing
      200,000 IU vitamin A or placebo at enrollment. MAIN OUTCOME MEASURES: Mean
      increments in weight and height during the 90 d period post supplementation.
      RESULTS: In all children, the mean increments in weight following supplementation
      were 0.66 kg (s.d. 0.5) and 0.64 kg (s.d. 0.6) in the vitamin A and placebo
      groups (P = 0.5). The mean increments in height were also similar in the two
      treatment groups (P = 0.5). Serum vitamin A was measured in 40 randomly selected
      children in each group; the proportion of subclinical deficiency (serum retinol <
      20 micrograms/dl) was 62.5% in those enrolled during summer (April through July)
      as compared to 21.1% in those enrolled during the remaining cooler months of the
      year (P = 0.02). In the children supplemented with vitamin A during summer, the
      mean increment in weight was 140 g more than those who received placebo (95%
      confidence interval CI 30-250); there was also a significant reduction in the
      proportion of children who were wasted (< -2 weight-for-height Z-score) at end
      study (Odds Ratio 0.53, 95% CI 0.28-1.0, P = 0.03). There was no significant
      impact of vitamin A on height increments in children supplemented during summer.
      CONCLUSION: Vitamin A supplementation in 12-59 month old children improves weight
      gain in the subsequent three months only in the summer season, but not during the
      rest of the year.

PMID- 9023464
TI  - Margarine intake and risk of nonfatal acute myocardial infarction in Italian
      women.
AB  - OBJECTIVES: Since a relation between trans-fatty acids and cardiovascular
      diseases has been described, we examined the relationship between margarine
      intake and nonfatal acute myocardial infarction (AMI) in Italian women. DESIGN:
      Hospital-based case-control study. SETTING: Northern Italy between 1983 and 1992.
      SUBJECTS: Cases were 429 women, aged 18-74 y, in hospital with diagnosis of AMI
      and 866 controls in hospital for acute, non-cardiovascular, non-neoplastic, non
      digestive, non-hormone-related conditions. ANALYSIS: Odds ratios (OR), with their
      95% confidence intervals (CI), were computed by unconditional multiple logistic
      regression analysis, including terms for age, education, body mass index,
      smoking, alcohol and coffee drinking, menopausal status, hormone replacement
      therapy and history of diabetes, hypertension and hyperlipidemia. RESULTS: Medium
      or high intake of margarine was associated with an increased risk of AMI
      (multivariate OR 1.5, 95% CI 1.0-2.2). Analysis in separate strata of covariates
      indicated that the association was independent of body mass index, history of
      hypertension and hyperlipidemia, and was greater in older women and in current
      smokers. CONCLUSIONS: If real, the association with margarine could explain about
      6% of AMI in this population of Italian women.

PMID- 9023465
TI  - The impact of zinc supplementation on Schistosoma mansoni reinfection rate and
      intensities: a randomized, controlled trial among rural Zimbabwean
      schoolchildren.
AB  - OBJECTIVES: To assess the effect of zinc supplementation on susceptibility to S.
      mansoni reinfections among schoolchildren. DESIGN: Randomized, double-blind,
      placebo-controlled trial. SETTING AND SUBJECTS: 313 rural Zimbabwean
      schoolchildren (144 boys and 169 girls), 11-17 y). INTERVENTIONS: Supplementation
      with zinc (30 or 50 mg) or placebo on schooldays for 12 months. Due to drought, a
      food programme was in operation during the last eight months of the study.
      OUTCOME MEASURES: S. mansoni and S. haematobium reinfection rates and
      intensities. RESULTS: There was no difference in reinfection rates between the
      zinc and placebo groups (25 vs 29%, P = 0.46). However, the median intensity of
      S. mansoni reinfection, although low in both groups, was significantly lower in
      the zinc than in the placebo group (7 vs 13 eggs per gram of faeces, P = 0.048).
      No difference in either S. haematobium reinfection rates or intensities were
      seen. CONCLUSIONS: Zinc supplementation reduced the intensity of S. mansoni
      reinfections. Although the intensities of reinfection were very low, the finding
      probably reflects a biological effect of zinc that could be of public health
      importance in settings with higher transmission.

PMID- 9023466
TI  - The impact of zinc supplementation on growth and body composition: a randomized,
      controlled trial among rural Zimbabwean schoolchildren.
AB  - OBJECTIVES: To assess the effect of zinc supplementation on growth and body
      composition among schoolchildren. DESIGN: Randomized, double-blind, placebo
      controlled trial. SETTING AND SUBJECTS: 313 rural Zimbabwean schoolchildren (144
      boys and 169 girls, 11-17 y). INTERVENTIONS: Supplementation with zinc (30 or 50
      mg) or placebo on schooldays for 12 months. Due to drought, a food programme was
      in operation during the last eight months of the study. VARIABLES: Weight,
      height, upper arm circumference, triceps skinfold thickness, and weight-for-age,
      height-for-age, weight-for-height, arm muscle-area-for-age and arm fat-area-for
      age Z-scores. RESULTS: Significant effects on weight gain (0.51 vs 0.14 kg, P =
      0.01), weight-for-age Z (-0.08 vs -0.14, P = 0.01) and arm muscle area-for-age Z
      score (0.10 vs 0.01, P = 0.03) were seen over the first three months, whereas no
      effects were seen over the full 12 months. CONCLUSIONS: Zinc deficiency impairing
      lean body mass and weight gain was documented. However, the effect of zinc seen
      over the first three months vanished during the last nine months when the food
      programme was in operation. Zinc deficiency may have persisted, but another
      nutrient may have become growth limiting during the last nine months.

PMID- 9023467
TI  - Eating habits, food and health related attitudes and beliefs reported by French
      students.
AB  - OBJECTIVES: To assess eating habits and some food related behaviours, beliefs and
      knowledge in educated young French adults. DESIGN: A standardized questionnaire
      administered in university classes. SETTING: University or 'Grandes Ecoles' of
      Paris and Dijon. SUBJECTS: 660 male and female French students. INTERVENTIONS:
      International survey; questionnaire composed of three major sections: (1) Health
      related attitudes such as substances used, dieting, health practices; (2) Beliefs
      concerning behaviour and health, including eating habits; (3) Knowledge, namely
      relevance of factors to diseases such as cancer or cardiovascular diseases.
      RESULTS: Gender, self-perception of body size, BMI and attempts to lose weight
      affected a number of behaviours. Average BMI corresponded to standard values.
      'Healthy' behaviours were often reported such as: avoiding fat and cholesterol,
      efforts to eat fruit and fiber. The French students showed a low frequency of
      snacking and a high regularity in having breakfast, especially respondents with
      lower BMI (females < or = 23 and males < or = 24.5 kg/m2). Beliefs about the
      importance of behaviours were closely associated with the performance of the
      behaviours. Awareness of the role of eating factors in cardiovascular diseases
      was observed. CONCLUSION: The meal and snack pattern in French students is very
      close to the traditional model. More food- and health-related behaviours and
      attitudes are reported by women than men. Some of them could be due to a genuine
      motivation for prevention and health in females or else to a greater wish to be
      thin. 'Desire to lose weight' is often reported although BMI values are normally
      low in this young population. Beliefs in the importance of a behaviour for health
      are correlated with the reported performance of the behaviours.

PMID- 9023468
TI  - Determinants of bone mineralization in 8 to 20 year old Finnish females.
AB  - OBJECTIVES: To study the determinants of bone mass and density in Finnish girls
      and young women. DESIGN: A cross-sectional study. SUBJECTS: One hundred and
      seventy six 8 to 20 year old female volunteers living in the city of Tampere,
      Finland. METHODS: Calcium intake was estimated from a 7 d calcium intake diary
      (CaD). Bone mineral content (BMC) and areal density (BMD) were measured by dual
      energy X-ray absorptiometry (DXA) at the lumbar spine, femoral neck and distal
      radius. Volumetric bone mineral apparent density (BMAD) was estimated from these
      DXA data. In addition, anthropometric characteristics, isometric muscle strength,
      and the Tanner stage were determined. Menstrual status and physical activity
      level were assessed by a questionnaire and personal interview. RESULTS: Body
      weight and Tanner stage were the most important determinants of BMC and BMD.
      Physical activity was the only not growth-related factor associated with BMC, BMD
      and BMAD. Therefore, it was examined in detail between the PA and NA groups. Site
      specific benefits varied from 5-7% for the BMC (lumbar spine and radius) and BMD
      (lumbar spine and femoral neck) and was about 5% for the BMAD (femoral neck).
      CONCLUSIONS: Body weight seems to be the most important determinant of the BMC
      and BMD of growing Finnish girls, but during puberty exercise may beneficially
      affect BMD at the loaded skeletal sites. Exercise may increase femoral BMAD
      during peripubertal years. There was no association between calcium intake and
      the bone variables, but the high level so calcium intake in all age groups of the
      study was likely to explain the lack of association.

PMID- 9023469
TI  - Evaluation of energy intake estimated by a diet history in three free-living 70
      year old populations in Gothenburg, Sweden.
AB  - OBJECTIVE: To evaluate the credibility of estimates of energy intake from a Diet
      History (DH) by cut off limits for the multiple of energy intake and basal
      metabolic rate (EI/BMRest) and by physical activity levels (PAL, total energy
      expenditure = TEE/BMR). DESIGN: Cohort study. SETTING: Departments of Geriatric
      Medicine and Clinical Nutrition, Goteborg University, Gothenburg, Sweden.
      SUBJECTS: 369 males and 440 females from three representative cohorts of free
      living individuals from the gerontological and geriatric population studies--H70.
      RESULTS: Man values for EI/BMR(est) was 1.50 and 1.60 in males and 1.48 and 1.49
      in females according to Schofield, Schofield and James (1985) and DHSS 41 (1991),
      respectively. A significant trend was seen when the sample was stratified at
      different levels of EI/BMR(est) with higher body weight, lower EI, higher
      proportion of energy from protein and lower of proportion energy from fat in the
      group with the lower values of EI/BMR(est). A significant difference was shown
      regarding food choice expressed as proportion of energy from ten defined food
      groups with respect to different EI/BMR(est) values. Lean body mass (LBM) by
      bioelectric impedance (BIA) correlated well with BMR according to DHSS 41 (1991),
      0.90 for males and 0.87 for females. CONCLUSION: Energy intake was underreported
      with the DH method--especially in over-weight individuals. Reported food choice
      varied with EI/BMR values. EI/BMR(est) limits are useful for detecting
      underestimation of habitual energy intake.

PMID- 9023470
TI  - The assessment of bioavailability of micronutrients: introduction.

PMID- 9023471
TI  - Bioavailability of iron.

PMID- 9023472
TI  - Bioavailability of iodine.

PMID- 9023473
TI  - Bioavailability of calcium and magnesium.

PMID- 9023474
TI  - Bioavailability of zinc.

PMID- 9023475
TI  - Bioavailability of selenium.

PMID- 9023476
TI  - Bioavailability of copper.

PMID- 9023477
TI  - Bioavailability of vitamin C.

PMID- 9023478
TI  - Bioavailability of Thiamin.

PMID- 9023479
TI  - Bioavailability of riboflavin.

PMID- 9023480
TI  - Bioavailability of vitamin B-6.

PMID- 9023481
TI  - Bioavailability of vitamin B12.

PMID- 9023482
TI  - Bioavailability of folate.

PMID- 9023483
TI  - Bioavailability of biotin.

PMID- 9023484
TI  - Bioavailability of pantothenic acid.

PMID- 9023485
TI  - Bioavailability of niacin.

PMID- 9023486
TI  - Bioavailability of flavonoids.

PMID- 9023487
TI  - Bioavailability of vitamin A.

PMID- 9023488
TI  - Bioavailability of vitamin D.

PMID- 9023489
TI  - Bioavailability of vitamin E.

PMID- 9023490
TI  - Bioavailability of carotenoids.

PMID- 9023491
TI  - Use and abuse of emergency department facilities.

PMID- 9023492
TI  - Approach to head trauma in childhood in a district general hospital.
AB  - The authors compared the management of children with head trauma in a general
      hospital in two different periods (1984-85 and 1988-90). In the first period 233
      cases were retrospectively evaluated; no guidelines were available at that time.
      In the second period 709 paediatric patients were treated following a protocol
      with indications for hospital admission and diagnostic procedures. In the
      clinical classes of milder symptoms (S0, S1, S2) a statistically significant
      reduction of hospital admission (p < 0.05) and skull radiography (p < 0.001) was
      achieved with the protocol without increasing the number of diagnostic errors,
      the incidence of clinical worsening because of an intracranial lesion was the
      same in the two periods (1.28% vs 1.27%). From our data and from the literature
      it emerges that it is necessary to clearly distinguish the children from 10 to 14
      years of age from the rest of the paediatric population for major risk of
      intracranial complications, as in this group the presence of a skull fracture
      represents a high risk factor, predictive of an intracranial haematoma. In the
      children under 10 years, the history and the clinical status have greater
      importance in establishing the diagnostic procedure to be followed. The
      asymptomatic cases (S0) or those with mild symptoms (S1) can be sent home with an
      instruction sheet explaining the symptoms of possible complications, without any
      further diagnostic procedures.

PMID- 9023493
TI  - A survey of treatment routines and educational level of health care providers in
      the initial phase of suspected acute myocardial infarction in Sweden in 1994.
      Swedish Working Group on Early Heart Attack Care.
AB  - The aim of this survey was to explore treatment routines with regard to early
      heart attack care at various hospitals in Sweden. All the hospitals in Sweden
      with a coronary care unit or its equivalent were sent a postal enquiry about
      early heart attack care including use of various medications and educational
      level of health care providers. In all, 84 of 86 hospitals (98%) answered the
      enquiry. Prior to hospital admission, 10% of the hospitals used thrombolytic
      agents, 10% used beta-blockers and 55% used aspirin. In only 4% of hospitals was
      thrombolytic treatment initiated in the emergency department and in 17% beta
      blockers were initiated. The proportion of acute myocardial infarction (AMI)
      patients who received thrombolytic treatment varied from 10% to more than 80%,
      with a mean value of 41%. The proportion of AMI patients who received intravenous
      beta-blockade varied from 0 to 93%, with a mean value of 24%. This survey
      indicates that the vast majority of hospitals in Sweden use thrombolytic agents
      in more than 30% of AMI patients and aspirin in more than 80% of AMI patients.
      The use of intravenous beta-blockade is lower than expected. Considering the
      strong association between the delay before instituting therapy and outcome, it
      is surprising that treatment is not initiated more frequently outside hospital or
      in the emergency department.

PMID- 9023494
TI  - An audit of in-hospital crash team interventions outside critical care areas.
AB  - All in-hospital interventions by the crash team of our hospital were recorded and
      evaluated retrospectively from 1 January 1992 to December 1994 and prospectively
      for 1995. The most frequent diagnosis was some type of cardiac arrest with a
      maximal incidence of 32.4% in 1994. Intubation was required in 58.7% of the cases
      in 1995. Outcome is better on surgical wards and for emergencies in the catheter
      laboratory compared with medical wards. The inappropriate overruling of the 'do
      not attempt resuscitation' (DNAR) policy eventually resulted in one survivor. We
      identified at least five cardiac arrest patients with an unacceptable delay in
      advanced life support. Our in-hospital critical incident registry resulted in a
      better policy for appropriate and timely intensive care unit referral.

PMID- 9023495
TI  - Emergency department walk-in patients study.
AB  - We conducted a 25-week study of the emergency department's (ED) walk-in patients
      at a university hospital, covering 20% of the total period by a Latin square
      method of 6-h blocks. One thousand eight hundred walk-in patients entered the
      study group. The walk-in population represents approximately 44% of the total ED
      population. Our results reveal that the study population was predominantly male,
      aged less than 40 years but somewhat younger than the general population and had
      a relatively stable place of abode. Trauma and medical patients were respectively
      46% and 53%. Eight-six per cent of the trauma patients came to the ED on their
      own initiative and less than 3 h after the accident or injury, while 43% of the
      medical patients were referred by a medical practitioner and had a relatively
      longer duration of symptoms. Forty-eight per cent of the medical patients visited
      the ED 12 h after the onset of symptoms. Although this study only concerned ED
      walk-in patients, the admission rate of medical patients is relatively high: 47%
      as opposed to the trauma patients' 10%. About 10% of the walk-in patients were
      classified as 'symptoms, signs and ill-defined conditions' according to the
      International Classification of Diseases 9. Fifty-two per cent of these patients
      were discharged home. This group of patients requires further investigation.

PMID- 9023496
TI  - Temporary observation in emergency medicine.
AB  - Modern emergency medicine requires the use of temporary observation (TO) to
      direct diagnostic and therapeutic decisions. The position of TO in the hospital
      structure has been well defined in the legal sense, inasmuch as it provides the
      preparatory stage for the final specialized medical treatment the patient will
      receive after admission. TO has become indispensable in emergency medicine to
      provide prompt treatment of critically ill patients and to clarify as rapidly as
      possible uncertain cases to avoid unnecessary admissions and transfers. To
      operate effectively, the service of TO must be provided well-trained staff,
      suitable physical facilities and support services, and access to rapid specialty
      consultations within the emergency room environment.

PMID- 9023497
TI  - Different clinical manifestations of meningococcaemia: three patient reports.
AB  - Neisseria meningitidis, a ubiquitous Gram-negative diplococcus, is responsible
      for a spectrum of clinical manifestations. This is illustrated by the history of
      three patients recently admitted to our hospital. Because of the possibly rapid
      and dramatic evolution, awareness for meningococcal diseases remains obligatory.
      Adequate antibiotic treatment instituted as soon as the diagnosis is suspected
      and early application of aggressive supportive care can lead to more favourable
      outcome.

PMID- 9023498
TI  - Comparative study of the efficacy of lysine acetylsalicylate, indomethacin and
      pethidine in acute renal colic.
AB  - The aim of this study was to compare the analgesic efficacy of intravenous lysine
      acetylsalicylate 1.8 g, indomethacin 100 mg and pethidine 100 mg in acute renal
      colic in a randomized double-blind clinical trial. One hundred and fifty patients
      with acute renal colic were divided into three groups. The first group received
      lysine acetylsalicylate 1.8 g, the second group received indomethacin 100 mg and
      the third group received pethidine 100 mg. The degree of pain relief was recorded
      5, 15, 30 and 60 min after intravenous administration of the drugs. There was no
      statistically significant difference between the degree of analgesia provided by
      pethidine and indomethacin. Lysine acetylsalicylate was less effective than
      indomethacin and pethidine. It is concluded that intravenous indomethacin is an
      effective alternative to intravenous pethidine in the treatment of acute renal
      colic. Intravenous lysine acetylsalicylate is inferior to intravenous
      indomethacin in treatment of acute renal colic.

PMID- 9023499
TI  - How to evaluate an emergency medical dispatch system and identify areas for
      improvement?

PMID- 9023500
TI  - Survival after laceration of the superior vena cava from blunt chest trauma.
AB  - Laceration of the superior vena cava is an unusual result of blunt trauma and is
      almost invariably lethal. A case caused by a high speed road traffic accident is
      presented; the factors relating to survival are discussed.

PMID- 9023501
TI  - A rare case of diplopia: medial inferior pontine syndrome or Foville's syndrome.
AB  - A case of medial inferior pontine syndrome or Foville's syndrome is described.
      The patient presented to the emergency department with an acute history of
      slurred speech, vertigo and diplopia as major complaints. He also mentioned the
      appearance of weakness and numbness in his left leg. The physical examination
      revealed a crossed neurological deficit (ipsilateral cranial nerve deficit with
      contralateral motor weakness) which is typical for posterior circulation stroke
      in the brainstem territory. In our patient the lesion was located in the right
      medial inferior pontine region. All the symptoms and signs disappeared within 24
      hours confirming the importance of a detailed physical and neurological
      examination of each patient presenting at the emergency department with a
      neurological deficit.

PMID- 9023502
TI  - Early electrocardiographic signs in acute massive pulmonary embolism.
AB  - As a result of the increasing accuracy in diagnosing acute pulmonary embolism by
      isotopic ventilation-perfusion scintigraphy and pulmonary arterial angiography,
      the electrocardiographic changes associated with acute cor pulmonale are being
      abandoned as a diagnostic tool for this life-threatening disease. Nevertheless,
      certain electrocardiographic findings can raise the suspicion of pulmonary
      embolism. In our view the electrocardiogram does have some merits in the
      emergency work-up of a patient with a high suspicion of pulmonary embolism. In
      this case report we emphasize the importance of the electrocardiographic findings
      which forwarded the diagnosis of pulmonary embolism. Hence the necessary invasive
      diagnostic and therapeutic measures, i.e. pulmonary arterial angiography and
      thrombolytic therapy, can be taken immediately after admission to the emergency
      department.

PMID- 9023503
TI  - Starling: the formulation of his hypothesis of microvascular fluid exchange and
      its significance after 100 years.

PMID- 9023504
TI  - The medullary raphe nuclei: a system for integration and gain control in
      autonomic and somatomotor responsiveness?

PMID- 9023505
TI  - An early transient current is associated with hyposmotic swelling and volume
      regulation in embryonic chick cardiac myocytes.
AB  - Hyposmotically induced changes in membrane conductance were measured in embryonic
      chick cardiac myocytes using conventional and perforated patch-clamp recording
      techniques; simultaneous measurements of cell volume were made from the video
      image of the voltage-clamped cell. Hyposmotic challenge was associated with a
      rapid, transient current coincident with the onset of cell swelling; cell volume
      subsequently recovered towards control values (regulatory volume decrease; RVD).
      The transient swelling-induced current (I(swell)) reversed at +15 mV, and was not
      found to be carried exclusively by any single ion in the physiological solutions.
      I(swell) was abolished by gadolinium (Gd3+), a blocker of stretch-activated ion
      channels, and was absent when the cytoskeleton was disrupted by treatment with
      cytochalasin B. I(swell) was also prevented when intracellular [Ca2+] was
      buffered with BAPTA AM. Under those experimental conditions which prevented the
      generation of I(swell), cell volume regulation failed so that the cells remained
      swollen in hyposmotic solution. Our data reveal a functional relationship between
      I(swell) and RVD, whereby I(swell) is a necessary prerequisite, although not
      exclusively sufficient, for volume recovery following cell swelling. We propose
      that I(swell) is an important early signalling event which activates subsequent
      mechanisms to regulate cell volume.

PMID- 9023506
TI  - Osmotic flow transients during acetylcholine stimulation in the perfused rat
      submandibular gland.
AB  - Osmotic stress was applied to the perfused rat submandibular gland during steady
      state fluid secretion. Alterations of perfusate osmolarity, by addition or
      withdrawal of sucrose or NaCl, caused transient changes in secretory rate during
      continuous stimulation with 1 microM acetylcholine (ACh). Hyposmotic perfusates
      transiently increased, and hyperosmotic perfusates transiently reduced, the
      secretory rate. The transients were attributed to changes in osmotic flow
      resulting from changes in the instantaneous transepithelial osmotic gradient. The
      time course of the change in interstitial osmolarity was determined by using a Cl
      electrode to record the changes in interstitial Cl- concentration following a
      step change in perfusate Cl- concentration. From the calculated changes in
      interstitial osmolarity and the resulting changes in secretory rate, the osmotic
      water permeability of the secretory pathway was estimated to be greater than 15.0
      +/- 1.2 microliter (mosmol 1-1)-1 min-1 (g wet weight)-1 (9.8 x 10(-6) +/- 0.8 x
      10(-6) l atm-1s-1g-1). The transepithelial gradient required to sustain steady
      state, ACh-evoked secretion would therefore be less than 16 mosmol l-1 NaCl,
      which is consistent with previous micropuncture data indicating that the luminal
      fluid is approximately isosmotic.

PMID- 9023507
TI  - L-type calcium current in catecholamine-induced cardiac hypertrophy in the rat.
AB  - This study investigates whether an increase in L-type calcium current (ICa) could
      explain the prolongation of the action potential associated with the cardiac
      hypertrophy produced by repeated administration of isoprenaline. Hypertrophy was
      induced by daily injection of isoprenaline (5 mg/kg i.p.) for 7 days in male
      Wistar rats. Under whole-cell voltage-clamp conditions, ICa was evoked in Na(+)-
      and K(+)-free solution, by step depolarizations from a holding potential of -45
      mV in single left ventricular myocytes isolated from control and hypertrophied
      rat hearts. In the test group, heart weight to body weight ratio and cell
      membrane capacitance were increased by 30 and 34%, respectively. Peak ICa was
      increased by 26% (control, -1.46 +/- 0.06 nA, n = 17; hypertrophy, -1.85 +/- 0.13
      nA, n = 19; P < 0.02). However, when normalized for cell capacitance, there was
      no significant difference in peak current density (control, -12.1 +/- 0.5 pA/pF;
      hypertrophy, -11.5 +/- 0.6 pA/pF). The voltage dependence of ICa was similar in
      both cell types. No change was observed either in the steady-state activation or
      inactivation kinetics, or in the time course of inactivation. The recovery from
      inactivation of ICa, when fitted with monoexponential function with time constant
      tau rec, was not changed significantly by hypertrophy (control, tau rec = 115 +/-
      23 ms, n = 9; hypertrophy, tau rec = 120 +/- 12 ms, n = 15). The increased
      calcium current occurs in parallel with the increase in cell size. The prolonged
      action potential duration seen in this model must be explained by changes in
      currents other than L-type calcium current.

PMID- 9023508
TI  - Effect of the potassium channel opener ZM260384 on skeletal muscle function
      during restricted blood flow in the anaesthetized cat.
AB  - The aim of the present experiment was to determine whether the potassium channel
      opener 2-(2,2-bis(difluoromethyl)-6-nitro-3,4-dihydro-2H-1, 4-benzoxazine-4
      yl)pyridine-N-oxide (ZM260384) was capable of accelerating the decline in
      skeletal muscle function during restricted blood flow in vivo. Cats (3.0-4.5 kg
      body weight) were anaesthetized with alphaxalone-alphadalone and breathed
      spontaneously following tracheotomy. Isometric tension was measured in the
      extensor digitorum longus-anterior tibialis (EDL-TA) muscle group. Ischaemia was
      induced by perfusing the hindlimb with the animal's own blood at a rate of 12.5
      ml min-1 using a roller pump and stimulating the common peroneal nerve to induce
      repetitive submaximal tetanic contractions in the EDL-TA. The number of
      stimulation voltage increments required each minute to maintain a constant level
      of submaximal mechanical output and the time to exhaustion were used as indices
      of the rate of tension decline. The rate of tension decline in the ischaemic EDL
      TA in the presence of ZM260384 at 3 mg kg-1, a maximally hypotensive dose
      predicted to be within the dose range required to exert direct effects on
      skeletal muscle, was measured and compared with the rate of tension decline in
      the presence of ZM260384 at 0.03 mg kg-1, also maximally hypotensive dose but
      below the predicted dose range for skeletal muscle effects. The number of voltage
      increments per minute was 1.93 +/- 0.07 and 1.48 +/- 0.14 (P < 0.05) in the
      presence of 3 and 0.03 mg kg-1 ZM260384, respectively. Time to exhaustion was
      17.5 +/- 4.2 and 7.2 +/- 0.8 min (P < 0.05) in the presence of 3 and 0.03 mg kg-1
      ZM260384, respectively. Given that there was no difference between these two
      groups in any haemodynamic variable measured, the results of the present study
      suggest that ZM260384 (3 mg kg-1) increases the rate of isometric force loss in
      ischemic skeletal muscle in vivo.

PMID- 9023509
TI  - Effects of nitric oxide on diaphragmatic muscle endurance and strength in pigs.
AB  - The aim of the study was to evaluate the effects of nitric oxide (NO) on
      diaphragmatic fatigue in fifteen anaesthetized, mechanically ventilated pigs,
      divided into three groups. The animals were pre-treated with indomethacin (3 mg
      kg-1, i.v.) to block the cyclo-oxygenase pathway. To group 1 pigs (n = 6) NG
      nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 i.v.) was administered as a
      bolus to block endogenous NO production, while group 2 pigs (n = 6) were infused
      with sodium nitroprusside (SNP, 0.023 mg kg-1, i.v.), a donor of NO. Group 3 pigs
      (n = 3) were used as the controls. We evaluated diaphragmatic strength by
      measuring the transdiaphragmatic pressure (P di) generated during bilateral
      phrenic nerve stimulation at 10, 20, 30 and 50 Hz, 15 V, while the diaphragmatic
      endurance was assessed by a 30s stimulation at 10 Hz, 15 V. Diaphragmatic index
      was assessed as the ratio of peak force between single twitches performed before
      and after the 30 s stimulation west. We also evaluated mean systemic (MAP) and
      pulmonary (MPAP) arterial pressures, pulmonary wedge pressure (PW), systemic
      (SVR) and pulmonary vascular resistance (PVR) and cardiac output (CO). L-NAME
      increased MAP, MPAP, PW, SVR and PVR, but decreased CO. SNP caused a decrease in
      MAP, MPAP, PW and SVR, while PVR and CO did not change. The main finding of this
      study was that diaphragmatic strength was not significantly weakened after L-NAME
      administration, except at 10 Hz, while it did not change after SNP infusion.
      However, both L-NAME and SNP caused significant decreases in diaphragmatic
      endurance capacity. The fatigue appearing after L-NAME is probably correlated
      with a decline in diaphragmatic blood flow, as evidenced by the increase in SVR
      and the decrease in CO, and consequently in oxygen supply. In contrast, the
      decrease in endurance capacity after SNP infusion can be attributed to a direct
      action of NO on skeletal muscle.

PMID- 9023510
TI  - Mechanical behaviour of rat skeletal muscle during fatiguing stretch-shortening
      cycles.
AB  - The effects of muscle fatigue on the mechanical efficiency of muscle work
      performance were studied in situ, in stretch-shortening cycles that resembled
      physiological conditions. The experiments were performed on the medial
      gastrocnemius muscles of seven rats. To calculate efficiency, a simple Hill-type
      model was used, consisting of the contractile component (CC) and the series
      elastic component (SEC). Mechanical efficiency was defined as the external work
      done by the muscle-tendon complex divided by the external work done upon the
      muscle-tendon complex plus work done by the CC. The fatiguing protocol consisted
      of a l Hz stretch-shortening cycle with a 0.3 duty factor (i.e. the muscle was
      stimulated for 300 ms in each cycle). In total, 240 cycles were imposed. The
      mechanical performance (work, force and mechanical efficiency) was determined
      throughout the fatiguing process. Fatigue reduced muscle power and force
      production to approximately 17 and 30%, respectively. SEC stiffness increased,
      but did not have any effect on muscle performance and probably reflects altered
      cross-bridge characteristics. Mechanical efficiency was enhanced during the
      imposed stretch-shortening cycles from 0.74 to 0.83. As a result of the lower
      peak forces, proportionally less series elastic energy was wasted during the
      relaxation period of each strength-shortening cycle in the fully fatigued
      muscles. These results indicate that, in vivo, the timing of muscle contractions
      in the fresh and the fatigued state may be different in order to perform muscle
      work efficiently. After a period of 30 min recovery, the condition of the muscles
      had (partially) returned to the fresh state in all aspects.

PMID- 9023511
TI  - Organization of the sural cutaneous input regulating the discharge of triceps
      surae gamma-motoneurones in the cat.
AB  - The organization of the cutaneous afferent influence on the discharge of gamma
      motoneurones has been investigated in the decerebrated, spinal cat. gamma
      Motoneurone discharges were recorded from cut nerve filaments. Time and frequency
      domain analyses were used to reveal the strength of coupling between gamma
      motoneurone discharge and cutaneous afferents excited by natural skin
      stimulation. Time domain analysis (cross-correlation) was also used to reveal the
      sigh (facilitation or inhibition) and time course of the cutaneous influence on
      individual gamma-motoneurones. Mechanical stimulation of discrete areas of skin
      within the sural nerve field caused facilitation or inhibition of individual
      gamma-motoneurones supplying the gastrocnemius and soleus muscles. In a few
      cases, a gamma-motoneurone facilitated by stimulation at one site could be
      inhibited from another location. The effect of cutaneous afferent stimulation was
      not evident in the decerebrated cat with intact spinal cord. The intensity of
      facilitation and inhibition was mapped for the sural nerve field. Facilitation
      had focus of highest intensity to stimulation applied between the calcaneum and
      lateral malleolus. The focus for inhibition was either the same as for
      facilitation or, more frequently, tended to be lateral and dorsal to the
      calcaneum at the edge of the sural field. Cutaneous stimulation at the edge of
      the sural field could also reduce the coherence between the discharges of gamma
      motoneurones, particularly at low frequencies of association (1-5 Hz), indicating
      disfacilitation of other sources of afferent input. The results reveal a detailed
      pattern of cutaneous inputs to the fusimotor system that could participate in a
      wide range of behavioural adjustments to stretch or contact of the skin at the
      heel.

PMID- 9023512
TI  - Quantification of efflux into the blood and brain of intraventricularly perfused
      [3H]thymidine in the anaesthetized rabbit.
AB  - Studies using choroid plexuses incubated in vitro have led to the conclusion that
      pyrimidine deoxyribonucleosides, such as thymidine, enter the brain predominantly
      through the blood-cerebrospinal fluid (CSF) barrier across the choroid plexuses.
      In order to examine this hypothesis, ventriculocisternal perfusions were carried
      out to determine the magnitude of the passage of [3H]thymidine from the CSF into
      the brain and blood. These experiments demonstrated that approximately 50% of the
      [3H]thymidine was eliminated from the CSF perfusate, some 41.6 +/- 5.6% passing
      into the blood and only 7.6 +/- 0.6% to the brain. Efflux into both the blood and
      brain was saturable, with a Km of 17.8 microM and a Vmax of 0.46 nM min-1, and
      partially nitrobenzylthioinosine (NBMPR) sensitive. However, a non-saturable
      component did exist (Kd, 13.8 microliters min-1). Overall, the rapid removal of
      [3H]thymidine from the CSF and its low uptake from the CSF into the brain
      suggests that the choroid plexuses would be an inefficient pathway for the entry
      of this pyrimidine deoxyribonucleoside into the brain.

PMID- 9023513
TI  - Acetylcholine-evoked potassium transport in the isolated guinea-pig pancreas.
AB  - In this study, K+ concentration was measured in effluent samples from superfused
      guinea-pig pancreatic pieces in control conditions and during stimulation with
      ACh, employing the technique of flame photometry. ACh (10(-7)-10(-5) M) evoked a
      dose-dependent and sustained increase in K+ concentration in the effluent (K+
      release). The removal of Ca2+ from the superfusing medium and the addition of 10(
      4) M EGTA caused a significant (P < 0.05) reduction in the ACh-evoked K+ efflux.
      Replacement of extracellular Cl- in the superfusing physiological salt solution
      with NO3- abolished the ACh-induced K+ efflux. In contrast, when Cl- was replaced
      with Br-, ACh still evoked marked K+ release. Pretreatment of pancreatic segments
      with the loop diuretic furosemide (10(-4) M) resulted in an inhibition of K+
      efflux elicited by ACh. Stimulation of pancreatic segments with the Na(+)-K(+)
      ATPase inhibitor ouabain (10(-3) M) caused a large efflux of K+. In the
      continuous presence of ouabain, ACh application elicited no further change in the
      K+ release. The results indicate that ACh-evoked K+ release from guinea-pig
      pancreatic segments is sensitive to ouabain, Cl-, furosemide and extracellular
      Ca2+ and that only the basal efflux is augmented by ouabain. The findings provide
      further evidence that a diuretic-sensitive coupled Na(+)-K(+)-Cl- cotransport
      system operates in the guinea-pig pancreas, as it does in other similar
      transporting epithelia, to bring about K+ mobilization.

PMID- 9023514
TI  - The validity of the recollection technique in micropuncture experiments on the
      rat kidney.
AB  - We tested the accuracy of the micropuncture technique by performing total
      collections of tubular fluid followed by immediate recollections from the same
      site. We studied thirty-one Wistar rats under different conditions of hydration
      and during maintenance infusions. To assure constancy of body fluid volumes the
      experiments were performed during continuous reinfusion of urine. Overall we
      performed 190 paired collections and immediate recollections from 147 proximal
      and 43 distal tubules. The mean values measured during the first collection were
      not different from the paired means obtained by recollection. Mean values (+/-
      S.E.M.) for first collection and recollection were: single nephron glomerular
      filtration rate (SNGFR), 34.7 +/- 1.3 vs. 34.2 +/- 1.3 nl min-1, P > 0.42;
      percentage reabsorption, 74 +/- 1 vs. 73 +/- 1, P > 0.53; absolute reabsorption,
      26.4 +/- 1.2 vs. 25.9 +/- 1.2 nl min-1, P > 0.47; collection rate, 8.4 +/- 0.6
      vs. 8.3 +/- 0.4 nl min-1, P > 0.92. When subdivided according to different
      physiological conditions and sampling sites, the results for the paired
      collection-recollection means were still not significantly different. The
      regression between collected and recollected SNGFRs had a slope of 0.96, r =
      0.85, P < 0.0001. In order to exclude the possibility that urine reinfusion per
      se could obscure putative differences in collection-recollection pairs, the
      effect of urine reinfusion was separately evaluated. We measured the differences
      obtained in collection-recollection pairs before and during urine reinfusion in
      twenty-eight tubules from eleven rats, a sample size that allows the detection of
      10% difference as significant. While SNGFR did not change, percentage
      reabsorption fell significantly from 76 +/- 3% before infusion to 60 +/- 3%
      during reinfusion, P < 0.003. We conclude that the recollection technique yields
      a reproducible estimate of SNGFR and tubular reabsorption, independent of the
      sampling site and of the technique used for fluid maintenance. Thus, it can be
      used to study the effect of different manoeuvres on the rate of proximal tubular
      transport. Urine infusion per se depresses proximal transport compared with that
      measured during maintenance with equivalent amounts of isotonic saline.

PMID- 9023515
TI  - Glucose, lactate and oxygen metabolism in the fetal pig during late gestation.
AB  - Using [U-14C]glucose tracer, rates of umbilical uptake, utilization and
      production of glucose, and of CO2 production from glucose carbon, were measured
      in seven chronically catheterized fetal pigs, when the sow was in the fed state,
      between 100 and 113 days of gestation (term, 114 +/- 2 days). At the same time,
      rates of umbilical O2 and lactate uptake were determined in all seven fetuses by
      the Fick principle. The mean fetal rates of umbilical glucose uptake, glucose
      utilization and CO2 production from glucose carbon were 38.4 +/- 4.2, 41.3 +/-
      5.2 and 126.9 +/- 12.6 mumol min-1 (kg fetal body weight)-1, respectively (n =
      7), No glucose production was therefore detected in the fetuses. Production of
      CO2 from glucose carbon accounted for 37.3 +/- 3.4% (n = 7) of the umbilical O2
      uptake, which averaged 340 +/- 13 mumol min-1 kg-1 (n = 7). There was also
      significant umbilical lactate uptake in the fetal piglets when the sow was in the
      fed state (32.6 +/- 10.4 mumol min-1 kg-1, n = 7, P < 0.05). No significant
      changes in fetal glucose, O2 or lactate metabolism were observed with increasing
      age towards term. The fetal rates of glucose metabolism and of umbilical uptake
      of O2 and lactate were not correlated with fetal blood glucose level. Hence,
      glucose is used for both oxidative and non-oxidative metabolism in utero and is
      an important, although not the sole, source of carbon for metabolic processes in
      the fetal pig during late gestation.

PMID- 9023516
TI  - The role of carotid chemoreceptors in the effects of hypoxia on renal blood flow
      in the late gestation sheep fetus.
AB  - Previous studies of the effect of hypoxia on fetal renal haemodynamics have
      demonstrated a fall, a rise or no change in renal blood flow (RBF). The
      underlying mechanisms are not understood but involve a balance between neural
      vasoconstrictor and opposing vasodilator mechanisms. Since carotid chemoreflex
      mechanisms contribute to vasoconstriction in other fetal vascular beds and in the
      adult renal vasculature, we examined their effects on RBF during 1 h of acute
      hypoxia in late gestation fetal sheep (n = 12). Renal blood flow was measured
      continuously and urine collected at 15 min intervals. Seven fetuses underwent
      bilateral section of the carotid sinus nerves (CSD fetuses). During hypoxia CSD
      fetuses showed a transient initial rise in RBF (P < 0.05) and then a subsequent
      fall (P < 0.05) to levels comparable with that recorded in intact fetuses. There
      was no change in urine output in either intact or CSD fetuses during hypoxia.
      Thus the initial fall in RBF during hypoxia is a carotid chemoreflex but other
      mechanisms, e.g. vasoconstrictor hormones, contribute to the sustained response.

PMID- 9023517
TI  - Effect of diets varying in nitrogen or phosphorus content on indicators of bone
      growth in lambs.
AB  - Growing lambs were fed diets low in nitrogen and phosphorus (LNLP), low in
      nitrogen and high in phosphorus (LNHP), high in nitrogen and low in phosphorus
      (HNLP) or high in nitrogen and phosphorus (HNHP) and the effects on bone growth
      and on blood and urinary bone marker levels or excretion rates were monitored.
      Plasma calcium concentrations were higher, and phosphorus concentrations lower,
      in lambs fed the low phosphorus diets but there were no differences in plasma
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations. Lambs fed both low
      phosphorus diets (LNLP and HNLP) had lower plasma osteocalcin and higher bone
      specific alkaline phosphatase concentrations than those fed the high phosphorus
      diets. Urinary pyridinoline and deoxypyridinoline excretion were also affected by
      treatment, with their rates of excretion being highest in lambs fed the diet low
      in both nitrogen and phosphorus (LNLP). Lambs fed the low phosphorus diets were
      lighter in weight at slaughter and had lighter bones that were less well
      mineralized than those fed the high phosphorus diets. Reducing the nitrogen
      content of the diet appeared to have little effect on bone composition. These
      results suggest that bone markers that have proved useful in the diagnosis and
      treatment of bone disease are sensitive to variation in nutrient supply and may
      prove useful in early detection of nutrient deficiencies that affect bone growth.

PMID- 9023518
TI  - Differential responses of glycogen synthase to ischaemia and ischaemic
      contraction in human skeletal muscle.
AB  - The importance of metabolic changes associated with contraction in the activation
      of glycogen synthase (GS) during recovery from exercise in human skeletal muscle
      has been investigated. Subjects underwent two experimental treatments: 15 s of
      ischaemic isometric contraction at 66% of maximal force, and 40 min circulatory
      occlusion. Biopsies were taken from the quadriceps femoris muscle at rest, at the
      end of each treatment, and 5 min post-treatment. The decreases in phosphocreatine
      (approximately 50%), and increases in glucose 6-phosphate (approximately 3-fold)
      and lactate (approximately 8-fold) were similar during contraction and occlusion,
      indicating similar degrees of anaerobic ATP turnover and glycogen breakdown.
      Glycogen breakdown during each treatment was estimated to correspond to < 5% of
      the basal muscle glycogen content. GS fractional activity decreased approximately
      10% after contraction and approximately 30% after occlusion (P < 0.05 vs.
      contraction). During recovery from contraction, GS fractional activity increased
      to 20% above the rest value, whereas no further change occurred during recovery
      from occlusion (P < 0.001 vs. recovery from contraction). These data demonstrate
      that the increase in GS fractional activity during recovery from isometric
      contraction does not require significant glycogen breakdown during the
      contraction, and is not a consequence of the measured metabolic changes
      associated with the contraction.

PMID- 9023519
TI  - Dissociation between metabolic and contractile responses during intermittent
      isometric exercise in man.
AB  - This study examines the temporal changes in high-energy phosphate and metabolic
      levels, and in force-generating capacity, during and after voluntary submaximal
      repetitive isometric exercise (RIE). Eight male subjects performed one-legged RIE
      with the knee extensors at 40% maximum voluntary contraction (MVC) target force
      (duty cycle: 6 s contraction, 4 s rest) in a 48 cm bore whole body 1.5 T
      superconducting magnet. Phosphocreatine (PCr), inorganic phosphate (P(i)), ATP
      and pH were measured every 9 s. Force-generating capacity was repeatedly measured
      using MVC force and electrically stimulated contractions (sequential train of
      impulses of 1-100 Hz). During RIE, MVC declined gradually by 56 +/- 5% (mean +/-
      S.E.M.). Electrically stimulated force also declined, with a disproportionally
      large drop in low-frequency force, seen as a decline from 0.76 +/- 0.02 to 0.33
      +/- 0.02 in 20:50 Hz force ratio. The PCr decline during RIE was 65 +/- 9%, in
      most subjects seen as a rapid initial drop followed by less or no further decline
      to exhaustion. pH declined in parallel by 0.18 +/- 0.04 units, whilst ATP levels
      remained unchanged throughout the exercise. PCr, P(i) and pH recovered to near
      control values within 5 min of exhaustion. Force, however, was not fully restored
      after 30 min recovery. The results support the hypothesis that fatigue from
      submaximal RIE is unrelated to changes in P(i) and H+ levels. The decline in
      20:50 Hz force ratio implies that fatigue may be associated with excitation
      contraction coupling impairment. No sudden changes were observed in mechanical or
      metabolic factors at exhaustion. Exhaustion was probably not caused by lack of
      substrates for ATP resynthesis, since pH had decreased only marginally.

PMID- 9023520
TI  - Intracellular pH and H+ buffering capacity in guinea-pigs with left ventricular
      hypertrophy induced by constriction of the thoracic aorta.
AB  - Intracellular pH (pHi) was measured in left ventricular myocytes from hearts
      hypertrophied by constriction of the thoracic aorta. There was a continuous
      relation between an increase in heart-to-body weight ratio and a decrease in pHi
      (mean +/- S.D., 7.06 +/- 0.18 pH units in control hearts vs. 6.87 +/- 0.17 pH
      units in hypertrophied hearts). Intracellular H+ buffering capacity (beta)
      increased as pHi fell, but the value of beta was independent of hypertrophy per
      se.

PMID- 9023521
TI  - Is human skeletal muscle capillary supply modelled according to fibre size or
      fibre type?
AB  - Analysis of muscle supply usually relies on estimating either the numerical
      capillary to fibre ratio or capillary density. Both indices are scale dependent,
      i.e. they vary with fibre size. We have examined the use of an alternative
      approach based on the anatomical supply area of individual capillaries, which
      allows the calculation of a local capillary to fibre ration or density based on
      area, rather than number of fibres. The results suggest that, in human skeletal
      muscle, capillary supply is primarily scaled according to fibre size, and is
      relatively independent of fibre type.

PMID- 9023522
TI  - How can evidence-based medicine help patients in general practice?

PMID- 9023523
TI  - The long-term use of benzodiazepines: patients' views, accounts and experiences.
AB  - BACKGROUND: Although a decrease in new prescribing has occurred for anxiolytic
      benzodiazepines, concerns have been raised that a 'core' of long-term users has
      been left behind. Typically, elderly people represent this 'core', using the
      benzodiazepines as hypnotics. OBJECTIVE: The present study focuses on the reasons
      why hypnotic benzodiazepines are used for protracted lengths of time. By
      examining patient experiences and cognitions, a deeper understanding may be
      gained of why patients continue to use benzodiazepines. METHODS: Elderly, long
      term users of benzodiazepine hypnotics were interviewed using a semi-structured
      interview procedure. A comparison group of non-users of the drugs were given a
      brief interview to collect comparative data. Interview data were analysed from
      transcripts using qualitative methodology; statistical comparisons between the
      groups were made using non-parametric statistics. RESULTS: The long-term users
      had significantly fewer hours of sleep per night than the non-users. There was
      some evidence of tolerance and a suggestion that symptoms of withdrawal were
      maintaining continual use. None of the long-term users had clean knowledge of
      what their doctors thought of their use of benzodiazepines. CONCLUSIONS: The data
      suggest that the power of the doctor may not be utilized to its full potential in
      the prevention of long-term use, that at least 50% of elderly benzodiazepine
      users would like to discontinue use, and that patients need information and
      advice on how to discontinue these drugs.

PMID- 9023524
TI  - "I've been crying my way"--qualitative analysis of a group of female patients'
      consultation experiences.
AB  - BACKGROUND AND OBJECTIVES: What do women patients, sick-listed for biomedically
      undefined musculoskeletal disorders, expect and experience when they consult a
      doctor? With the purpose to learn more about this, a qualitative interview study
      was conducted. METHODS: Twenty women participated. They were patients at an urban
      health care centre in northern Sweden. Data were gained through repeated, semi
      structured interviews, and analysed according to grounded theory. RESULTS: The
      participants described an atmosphere of distrust in the consultation. They had
      felt ignored, disregarded and rejected by doctors, and had worked out strategies
      to keep up medical attention in their search for a creditable diagnosis. They
      were somatizing, claiming under cover, and pleading, to catch the doctor's
      interest. In addition, they upheld their self-respect by mystifying and
      martyrizing themselves and their symptoms, and by condemning physicians as
      ignorant. DISCUSSION: The patient's consultation experiences are discussed from
      different aspects; the biomedical framework, the power asymmetry, and the
      gendered positions of patient and doctor. The findings indicate the importance of
      making doctors aware of the context behind frustrations in doctor-patient
      interaction.

PMID- 9023525
TI  - General practice receptionists' attitudes and beliefs towards preventive medicine
      before and after training and support interventions.
AB  - OBJECTIVES: Receptionists are an integral part of the primary care service. We
      aimed to discover their views on preventive medicine issues. METHOD: One hundred
      and fifty receptionists from general practices in Sydney, Australia, completed a
      questionnaire on their attitudes and beliefs towards preventive medicine and
      brief intervention for alcohol. They were matched according to practice variables
      into a control, no, minimal, or maximal training and support condition. In all
      conditions except the control condition, receptionists received 5 minutes of
      initial training in implementing a brief intervention programme; the amount of
      ongoing support varied across conditions. Attitudes and beliefs were re-assessed
      3 months later. RESULTS AND CONCLUSIONS: The results indicated that when no
      training and support were given, receptionists developed negative views towards
      being involved in preventive medicine activities. When training and support were
      provided, these negative effects were abolished.

PMID- 9023526
TI  - Differences in meanings of health: and exploratory study of general practitioners
      and their patients.
AB  - OBJECTIVES: Many health-related behaviours, particularly non-compliance with
      medical advice, seem irrational to professionals. 'Health' is a planned goal of
      health care but the extent to which doctors and patients agree about its meaning
      is unknown. We hypothesized that general practitioners (GPs) construe health as
      an absence of disease (medical model) to a greater extent than their patients in
      general and that asthmatic patients construe health in a manner biased to
      preserve their self-esteem. METHOD: Forty-eight patients with asthma, 48 matched
      well patients and 34 GPs each gave up to six personal definitions of 'health'.
      Their definitions were classified into nine categories of meaning. RESULTS:
      Results showed significant differences in the ways in which general practitioners
      and patients defined 'health' (chi-squared between GPs and asthmatics was 98, df
      = 7, P < 0.0001; chi-squared between GPs and well patients was 85, df = 7, P <
      0.0001). As hypothesized, the category of meaning used most by general
      practitioners was an absence of disease, whereas patients expressed the meaning
      of health in terms of 'being able', 'taking action' and 'physical well-being'.
      Support for the second hypothesis, although consistent, was weak. CONCLUSIONS:
      The way in which differences in beliefs provide a basis for understanding
      apparently irrational patient behaviours is discussed in the context of social
      identity theory. Implications for doctor-patient communication and the
      psychological validity of subjective health status and quality of life measures
      are also noted.

PMID- 9023528
TI  - Sampling for qualitative research.
AB  - The probability sampling techniques used for quantitative studies are rarely
      appropriate when conducting qualitative research. This article considers and
      explains the differences between the two approaches and describes three broad
      categories of naturalistic sampling: convenience, judgement and theoretical
      models. The principles are illustrated with practical examples from the author's
      own research.

PMID- 9023527
TI  - General practitioners' views about the need for a stress support service.
AB  - OBJECTIVES: We wished to determine general practitioners' (GPs') views regarding
      the need for a stress support service. METHOD: A postal questionnaire survey of
      GPs' views (n = 274) about the need for a stress support service, and what form
      such a service might take, was undertaken on Tyneside. RESULTS: A response rate
      of 79.5% was achieved with one reminder. A majority (78.8%) were in favour of a
      stress support service for GPs, the most popular options for the service being
      independently accessed counsellors and stress management groups. Over 90% of
      respondents thought that support should be available to any doctor, and 65% that
      is should be available to all primary health care team members. The five most
      commonly mentioned causes of stress were: time and workload problems; on call;
      expectations and demands of patients; administration and paperwork; and
      complaints and fear of litigation. CONCLUSIONS: The survey demonstrated
      widespread concern amongst GPs on Tyneside about stress levels and considerable
      interest in the idea of stress support. However, a variety of approaches would be
      required to meet the range of perceived needs, and any such services should be
      made accessible to all practitioners regardless of whether they are actually
      suffering from stress, as well as to other members of the primary health care
      team.

PMID- 9023529
TI  - Sampling for qualitative research using quantitative methods. 1. Measuring GPs'
      attitudes towards discussing smoking with patients.
AB  - BACKGROUND: Interview studies which employ qualitative methodology are often
      concerned with classifying behaviours or attitudes and an ideal sample of
      research subjects displays variety in the attitudes or behaviours under scrutiny.
      OBJECTIVE: This paper describes the development of a questionnaire which measures
      GPs' attitudes towards discussing smoking with patients with the intention of
      using this instrument to select GPs with diverse views for a qualitative
      interview study. METHOD: Thirteen attitude statements with an accompanying Likert
      type scale were completed by 327 GPs in one FHSA area. Factor analysis of
      responses produced two subscales: 'perceived efficacy' and 'enthusiasm'.
      Reliability and validity of these were examined. RESULTS: Each subscale had good
      internal reliability and preliminary exploration of construct validity supported
      the notion that the subscales were valid. CONCLUSION: The use of this type of
      instrument in sampling GPs for qualitative studies could be effective for
      selecting subjects with a diversity of views towards the research topic.

PMID- 9023530
TI  - Sampling for qualitative research using quantitative methods. 2. Characteristics
      of GPs who agree to video-taping of consultations.
AB  - BACKGROUND AND OBJECTIVES: Studies using video-recordings of GPs' consultations
      have been important in investigating GPs' clinical behaviour. Unfortunately, the
      characteristics of participating GPs are rarely described, making it difficult to
      assess how representative they are or how generalizable the studies' results can
      be. This paper documents the recruitment of 53 GPs to a research project which
      involved video-recording their consultations to determine how GPs approach the
      topic of smoking cessation with patients. METHODS: The Attitudes to Smoking
      Advice Questionnaire was used to select GPs with diverse attitudes towards
      discussing smoking with patients. RESULTS: Out of 123 GPs who were eligible to
      take part, 53 (43.1%) agreed. GPs who agreed to become research subjects were
      younger, more likely to work in teaching or training practices and more likely to
      be current members of the RCGP. CONCLUSIONS: When planning studies which utilize
      video-recordings of GPs' consultations, researchers should give consideration to
      how this apparent self-selection by participating GPs could influence research
      results.

PMID- 9023531
TI  - Facing future challenges in general practice: a clinical method with computer
      support.
AB  - This paper proposes a clinical method for general practice which is patient
      centred and which ensures that the doctor's agenda is supported to secure 'best
      practice'. It encompasses self-learning for GPs which is patient-focused and
      describes the encouragement and support of patient self-care. The method attempts
      to be pragmatic and usable within GPs' available time. The method, however, is
      not solely focused on the GP; it encompasses the primary health care team and the
      patient. It uses clinical information systems to assist in the management of the
      patient care plan, to supply information to the GP and patient, in order to aid
      shared decision making and to quality assure clinical activity. It goes further
      by extending the care process to handle 'virtual' encounters in which the
      clinical information systems play a central role.

PMID- 9023534
TI  - The method of Balint group work and its contribution to research in general
      practice.

PMID- 9023533
TI  - Measuring man: some problems of method.

PMID- 9023535
TI  - The application of anthropological methods in general practice research.

PMID- 9023536
TI  - The use of historical study in medical research.

PMID- 9023537
TI  - Qualitative research: challenges for integration support and dissemination.

PMID- 9023539
TI  - A galectin links the aggregation factor to cells in the sponge (Geodia cydonium)
      system.
AB  - The cDNA for the full-length lectin from the marine sponge Geodia cydonium was
      cloned. Analysis of the deduced aa sequence revealed that this lectin belongs to
      the group of galectins. The full-length galectin, which was obtained also in a
      recombinant form, has an M(r) of 20,877; in the processed form it is a 15 kDa
      polypeptide. The enriched aggregation factor from G.cydonium also was determined
      to contain, besides minimal amounts of the galectin, a 140 kDa polypeptide which
      is involved in cell-cell adhesion. Monoclonal antibodies have been raised against
      this protein; Fab' fragments prepared from them abolished cell-cell
      reaggregation. Cell reaggregation experiments revealed that the aggregation
      factor is an essential component in the aggregation process but it requires
      likewise the presence of the galectin. Antibodies against the galectin blocked
      the aggregation factor-mediated cell adhesion. A plasma membrane component was
      identified (a 29 kDa polypeptide) which interacted with the aggregation factor in
      the presence of galectin; binding could be blocked both by antibodies against the
      galectin as well as against the aggregation factor. Immunohistochemical analysis
      revealed that spherulous cells contain the galectin but not the aggregation
      factor. By laser scanning microscopy, it is shown that both the aggregation
      factor and the galectin are located at the rim of the cells. From these data we
      conclude that the G.cydonium aggregation factor binds to the cells via a galectin
      bridge.

PMID- 9023540
TI  - Inhibition of glycoprotein processing by L-fructose and L-xylulose.
AB  - A number of unusual and rare carbohydrates were tested as potential inhibitors of
      various glycosidases, as well as inhibitors of N-linked oligosaccharide
      processing. The best inhibitors of several arylglycosidases and of glucosidase I
      were L-xylulose and L-fructose. Both of these sugars showed some inhibitory
      activity towards yeast alpha-glucosidase but were inactive against beta
      glucosidase and other arylglycosidases. The inhibition of yeast alpha-glucosidase
      by L-xylulose was of a competitive nature and required a concentration of 1 x 10(
      5) M for 50% inhibition. Both L-xylulose and L-fructose also inhibited the
      purified soybean glucosidase I, with 50% inhibition occurring at about 1 x 10(-4)
      M, but showed no inhibitory activity against soybean glucosidase II. When
      influenza virus-infected MDCK cells were raised in the presence of L-xylulose,
      there was a dose-dependent inhibition in the formation of complex types of
      oligosaccharides on the viral glycoproteins consistent with the inhibition of the
      processing glucosidase I. This inhibition resulted in the occurrence of
      oligosaccharides on the viral glycoproteins that were characterized as
      Glc3Man9(GlcNAc)2 structures. L-Fructose also inhibited glycoprotein processing
      in cell culture, and the inhibition resulted in the formation of similar
      oligosaccharides to those seen with L-xylulose. However, L-fructose was a poorer
      inhibitor than L-xylulose and required much higher concentrations for the same
      degree of inhibition. Neither of these compounds inhibited protein synthesis or
      the formation of lipid-linked saccharides in culture MDCK cells, even when tested
      at concentrations of 5 mg/ml (about 30 mM) of culture media.

PMID- 9023541
TI  - Cloning and analysis of the MNN4 gene required for phosphorylation of N-linked
      oligosaccharides in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae MNN4 gene, which is involved in mannosylphosphate
      transfer from GDP-mannose to N-linked oligosaccharide, has been cloned from a
      lambda phage containing a yeast chromosome XI DNA fragment. The MNN4 ORF encodes
      a protein of 1178 amino acids. The deduced amino acid sequence shows a topology
      of type II membrane proteins and has a unique repeated sequence of lysine and
      glutamic acid at the C-terminus. Disruption and overexpression of MNN4 led to a
      decrease and increase, respectively, of the mannosylphosphate content in cell
      wall mannans prepared from both mnn4 and wild type strains. A dramatic decrease
      of mannosylphosphate occurs in delta mnn4 mutans. The results from genetic and
      biochemical experiments combine to suggest that Mnn4p is required to mediate
      mannosylphosphate transfer in both the core and outer chain portions of N-linked
      oligosaccharides.

PMID- 9023542
TI  - Dolichyl-phosphomannose synthase from the archae Thermoplasma acidophilum.
AB  - Archae (formerly Archaebacteria) comprise an entire kingdom of organisms placed
      halfway between prokaryotes and eucaryotes in evolution. This class of organisms
      lacks murein cell wall and is devoid of organelles, yet Archae synthesize and
      export N-linked and O-linked glycoproteins utilizing only the plasma membrane.
      Study of glycosylation systems in Archae is extremely interesting because the
      plasma membrane must perform many functions normally carried out by the
      endoplasmic reticulum and Golgi in eucaryotes. This report represents the first
      glycosyl transferase system enzyme demonstrated from archae showing a functional
      relationship with homologous eucaryotic enzymes. Archae dolichyl-phosphoryl
      mannose synthase was purified 1070-fold from Thermoplasma acidophilum by column
      chromatography on Sephacryl S-200, Cibacron blue 3GA-agarose, Octyl-Sepharose,
      and hydroxylapatite in the presence of 0.2% polioxyethylene 9 lauryl ether. The
      enzyme activity was stimulated by MgCl2 (20 mM optimum) and exhibited a pH
      optimum at 6.0. Although the native polyisoprenoid has not been isolated or
      characterized, the enzyme prefers dolichyl phosphate (dol-P) to C55-polyisoprenol
      as an acceptor, and the Km value for dol-P was calculated to be 2.6 microM.
      Amphomycin, an inhibitor of dol-P-Man synthase, blocked mannosyl transfer to the
      endogenous lipids, proteins, and to dol-P; 100 micrograms/ml amphomycin inhibited
      97% of mannosyl transfer to dol-P, and 50% to endogenous acceptors, indicating
      direct transfer from GDP-mannose to some intermediates or final structures. The
      size range of [3H]Man-oligosaccharides from acid-labile manno-lipid product was
      from dp 1 to 4. dol-P-Man synthase activity could be correlated directly with a
      42 kDa band on SDS/polyacrylamide gel electrophoresis.

PMID- 9023543
TI  - Ultrastructure of Kurloff body proteoglycans after high pressure freezing,
      cryosubstitution and postembedding staining with cuprolinic blue.
AB  - Very high pressure freezing and cryosubstitution of Kurloff cells preserves the
      ultrastructural morphology of Kurloff bodies, particularly the myelin figures, as
      shown by embedding in epoxy resin and conventional postembedding staining. It
      also preserves the Kurloff body proteoglycans as more expanded spindle-like
      shapes than does fixation with formaldehyde at atmospheric pressure. But,
      proteoglycans were not discernible in the Kurloff body matrix on either unstained
      or conventionally stained thin sections. The Kurloff body skeleton of
      proteoglycans in their native expanded shape was stained with the electron-dense
      cationic ministain cuprolinic blue, using thin sections embedded in LR white. The
      mean equatorial diameter of the spindles was 20-30 nm, while the collapsed
      filaments produced by aldehyde fixation were about 10-15 nm wide. The spindles
      were often about 200-300 nm long but could be much longer, depending on the plane
      of the section. Thus, high pressure freezing, freeze substitution, embedding in
      LR white, and staining with cationic dyes such as phthalocyanins seems to be a
      convenient way of visualizing intracellular proteoglycans that are well preserved
      and in very much like their native expanded state.

PMID- 9023544
TI  - Ion exchange HPLC microanalysis of chondroitin sulfate: quantitative
      derivatization of chondroitin lyase digestion products with 2-aminopyridine.
AB  - Sulfated glycosaminoglycans such as chondroitin sulfate are composed of three
      structural domains, a linkage oligosaccharide, connecting the chain to the core
      protein, a variably sulfated disaccharide repeat structure within the chain and a
      nonreducing terminal, and these domains may confer specific functions on
      particular chain populations. We report here a new and highly sensitive method
      for the detection and quantitation of all nonreducing terminal residues and
      internal disaccharides obtained by chondroitinase ABC or ACII digestion of
      aggrecan chondroitin sulfate. The procedure involves a quantitative reductive
      animation of the reducing ends of sulfated mono- and disaccharide chondroitinase
      products with 2-aminopyridine and boranedimethylamine. All derivatized
      saccharides can be separated and quantitated by fluorescence in a single
      chromatographic step on an AS4A anion exchange column, eluted with a gradient (0
      500 nM) of sodium trifluoroacetate. The reproducibility and stability of the
      derivatisation, together with the sensitivity of the chromatography system,
      allowed for routine quantitation in the range of 3-500 pmol of reducing group
      (corresponding to about 1.5-250 ng of disaccharide or 0.75-125 ng of
      monosaccharide). Moreover, the fluorescence yield (fluorescence area units per
      pmol of reducing group) was virtually identical for all saccharides analyzed.
      Application of this method to an analysis of aggrecan purified from calf
      epiphyseal cartilage and from rat chondrosarcoma chondrocyte cultures allowed a
      precise identification and quantitation of the internal disaccharides and the
      nonreducing terminal structures, together with an estimation of the number
      average molecular weight of CS chains in these aggrecan preparations.

PMID- 9023545
TI  - Structure/activity studies of anti-inflammatory peptides based on a conserved
      peptide region of the lectin domain of E-, L- and P-selectin.
AB  - Previously, it was established that the peptide YYWIGIRK-NH2 inhibits both
      myeloid cell adhesion to selectins in vitro and neutrophil influx into
      inflammatory sites in vivo (Briggs et al., 1995). Initial structure/activity
      studies revealed that at least one Y residue at the N-terminus of the peptide was
      essential for these bioactivities but that the C-terminal K residue was
      unnecessary for inhibitory activity. We have now synthesized a new series of
      peptides which contain single residue substitutions at each position of the
      reference peptide, YYWIGIR-NH2, and have tested these peptides for inhibitory
      activity in a selectin cell binding assay. In addition, peptides containing
      single D-amino acids at selected positions, or an all D-configured reference
      peptide sequence, or the retro-inverso version (rigiwyy-NH2) of the reference
      peptide sequence have also been analyzed for inhibitory activity in the same
      assays. Finally, the ability of the reference peptide and a specifically designed
      control sequence (YY(AIB)IGIR-NH2) to discriminate between potential synthetic
      saccharide ligands, including sialyl-Lewis x, Lewis x, and sialyl-N-acetyl
      lactosamine, was investigated using isothermal titration calorimetry. The results
      of these studies demonstrate that whereas many single amino acid substitutions
      are tolerated in the peptide without complete loss of inhibitory activity,
      substitution at some positions (e.g., the W residue) results in relatively
      inactive compounds, clearly pointing to the importance of these residues in
      making critical contacts with the appropriate saccharide ligand. Titration
      calorimetry revealed that the reference peptide does not discriminate between
      Lewis x or sialyl-Lewis x in vitro, but binds these saccharides with nearly 40
      fold higher affinity (KD 25 microM) than the nonfucosylated trisaccharide, sialyl
      N-acetyl-lactosamine. We can infer from these studies that the presence of a
      sialyl group per se, is not a requisite for complex formation between the
      reference peptide and its saccharide ligand. Substitution of single D-amino acid
      residues at various positions in the reference peptide sequence reduces or
      eliminates all inhibitory properties. However, the all D-configured peptide or
      the retro-inverso peptide sequence have greater activity than the all L
      configured reference peptide in the in vitro biological assays, and each was an
      effective inhibitor of neutrophil infiltration in a thioglycolate-induced mouse
      peritonitis model. These results, combined with the results of titration, allow
      us to conclude that binding between the reference peptide and its saccharide
      ligand, which affords its inhibitory properties, is mediated by the presence of a
      contiguous, nonpolar surface, or face, presented at the N-terminus of the
      reference peptide, likely encompassing the sequence YYWI. Furthermore, the W
      plays a critical role in binding, probably through formation of an essential
      hydrogen bond with a suitably juxtaposed group carried on the saccharide ligand.

PMID- 9023546
TI  - Identification of a GDP-L-fucose:polypeptide fucosyltransferase and enzymatic
      addition of O-linked fucose to EGF domains.
AB  - An assay of GDP-fucose:polypeptide fucosyltransferase has been established. The
      enzyme catalyzes the reaction that attaches fucose through an O-glycosidic
      linkage to a conserved serine or threonine residue in EGF domains. The assay uses
      recombinant human factor VII EGF-1 domain as acceptor substrate and GDP-fucose as
      donor substrate. Synthetic peptides with sequences taken from five proteins
      previously shown to contain O-linked fucose (Harris and Spellman, 1993;
      Glycobiology, 3, 219-224) did not serve as efficient acceptor substrates. These
      synthetic peptides did not compromise complete EGF domains and did not contain
      all six cysteine residues that define the EGF structure. Therefore, the enzyme
      appears to require more than just a consensus primary sequence and likely
      requires that the EGF domain disulfide bonds be properly formed. The enzymatic
      reaction showed linear dependency of its activity on time, amount of enzyme, and
      substrates. Although the enzyme did not exhibit an absolute requirement for Mn2+,
      enzymatic activity did increase ten fold in the presence of 50 mM MnCl2. The in
      vitro glycosylation reaction resulted in complete conversion of the acceptor
      substrate to glycosylated product, and characterization of the purified product
      by electrospray mass spectrometry revealed that one fucose was added onto the
      polypeptide. Most of the enzymatic activity was found to be in the soluble
      fraction of CHO cell homogenates. However, when enzyme was prepared from rat
      liver in the presence of protease inhibitors, 37% of the activity was recovered
      by Triton X-100 extraction of the membrane particles after extensive aqueous
      washes. The result suggests that the enzyme is probably a membrane protein and,
      by analogy with other glycosyltransferases, probably has a 'stem' region that is
      very susceptible to proteolysis.

PMID- 9023547
TI  - Comparative cross-linking activities of lactose-specific plant and animal lectins
      and a natural lactose-binding immunoglobulin G fraction from human serum with
      asialofetuin.
AB  - Plant and animal lectins bind and cross-link certain multiantennary
      oligosaccharides, glycopeptides, and glycoproteins. This can lead to the
      formation of homogeneous cross-linked complexes, which may differ in their
      stoichiometry depending on the nature of the sugar receptor involved. As a
      precisely defined ligand, we have employed bovine asialofetuin (ASF), a
      glycoprotein that possesses three asparagine-linked triantennary complex
      carbohydrate chains with terminal LacNAc residues. In the present study, we have
      compared the carbohydrate cross-linking properties of two Lac-specific plant
      lectins, an animal lectin and a naturally occurring Lac-binding polyclonal
      immunoglobulin G subfraction from human serum with the ligand. Quantitative
      precipitation studies of the Lac-specific plant lectins, Viscum album agglutinin
      and Ricinus communis agglutinin, and the Lac-specific 16 kDa dimeric galectin
      from chicken liver demonstrate that these lectins form specific, stoichiometric
      cross-linked complexes with ASF. At low concentrations of ASF, 1:9 ASF/lectin
      (monomer) complexes formed with both plant lectins and the chicken lectin. With
      increasing concentrations of ASF, 1:3 ASF/lectin (monomer) complexes formed with
      the lectins irrespective of their source or size. The naturally occurring
      polyclonal antibodies, however, revealed a different cross-linking behavior. They
      show the formation of 1:3 ASF/antibody (per Fab moiety) cross-linked complexes at
      all concentrations of ASF. These studies demonstrate that Lac-specific plant and
      animal lectins as well as the Lac-binding immunoglobulin subfraction from
      specific stoichiometric cross-linked complexes with ASF. These results are
      discussed in terms of the structure-function properties of multivalent lectins
      and antibodies.

PMID- 9023549
TI  - Evaluation of the early processing routes of N-linked oligosaccharides of
      glycoproteins through the characterization of Man8GlcNAc2 isomers: evidence that
      endomannosidase functions in vivo in the absence of a glucosidase blockade.
AB  - Since it has become apparent that the early processing of the N-linked
      oligosaccharides of glycoproteins can proceed by several routes, we undertook to
      determine whether the isomeric nature of Man8GlcNAc2, which is the first
      intermediate with the potential for structural diversity, can provide information
      relating to the pathways utilized in various intact cultured cells as well as in
      the total membrane fraction derived from these cells (BW5147.3, HepG2, HL60, F-9,
      and MDCK). With the use of kifunensine (KIF) to block processing by Golgi
      mannosidase I, it could be shown that a substantial amount of Man8GlcNAc2
      components in which the terminal mannose is missing in the alpha 1,3-linked and
      alpha 1,6-linked chain (isomers A and C, respectively) are produced, although in
      the absence of the inhibitor only the B-isomer, in which the mannose of the
      middle chain has been excised, was apparent. Our findings in vivo and in vitro
      suggest that the distinctive Man8GlcNAc2 product of endomannosidase (isomer A)
      and of ER mannosidase II (isomer C) are not evident in the absence of KIF, since
      they are rapidly degraded by Golgi mannosidase I, which is located in an
      intracellular compartment distal to the other two enzymes and itself exclusively
      generates the Man8GlcNAc2 isomer B. Investigations carried out in HepG2 cells
      indicated that glycoproteins with N-linked oligosaccharides whose processing has
      been blocked by KIF at the Man8GlcNac2 isomer A and C stage can nevertheless be
      effectively secreted. The observation that isomer A of Man8GlcNAc2 is a specific
      product of endomannosidase action made it possible to demonstrate the action of
      this enzyme in vivo without employing a glucosidase blockade and to show that a
      substantial amount of the deglucosylation of N-linked oligosaccharides is carried
      out by this enzyme.

PMID- 9023548
TI  - Targeting of active rat alpha 2,3-sialyltransferase to the yeast cell wall by the
      aid of the hsp 150 delta-carrier: toward synthesis of sLe(x)-decorated L-selectin
      ligands.
AB  - Interactions between selectins and their oligosaccharide-decorated ligands play a
      crucial role in the initiation of leukocyte extravasation. We have shown that
      synthetic multivalent sialyl Lewis x glycans inhibit strongly the adhesion of
      lymphocytes to endothelium at sites of inflammation. However, enzyme-assisted
      synthesis of these oligosaccharides si hampered by the lack of sufficient amounts
      of specific glycosyltransferases. We report here the construction of
      Saccharomyces cerevisiae strains expressing the soluble catalytic ectodomain of
      rat Gal(beta)1-3/4GlcNac alpha 2,3-sialyltransferase (ST3Ne) fused to the C
      terminus of the hsp150 delta-carrier polypeptide. The hsp150 delta-carrier, which
      is an N-terminal fragmented of a natural secretory protein of yeast, is able to
      confer secretion-competence to several heterologous proteins, which otherwise
      remain in the yeast endoplasmic reticulum. The ST3Ne portion of the hsp 150 delta
      ST3Ne fusion protein adopted an enzymatically active conformation and was N
      glycosylated and disulfide-bonded. Hsp150 delta-ST3Ne was secreted with a half
      time of about 7.5 min and remained intercalated in the cell wall, which covers
      the yeast plasma membrane. About 110 mU of sialyltransferase per litre was
      produced in 16 h. Whole live yeast cells were able to transfer sialic acid from
      CMP-NeuNAc to N-acetyllactosamine yielding alpha 2,3-sialyl-N-acetyllactosamine,
      as evidenced by paper chromatography, cleavage by linkage-specific sialidase, and
      NMR analysis. Our data suggest that yeast cells externalizing mammalian
      glycosyltransferases with the aid of the hsp150 delta-carrier could provide a
      source of enzymes for synthesis of valuable oligosaccharides.

PMID- 9023550
TI  - Structural characterization of novel oligosaccharides of cell-surface
      glycoproteins of Trypanosoma cruzi.
AB  - Affinity-purified glycopeptides were prepared from Trypanosoma cruzi using the
      carbohydrate-specific monoclonal antibody WIC29.26. These glycopeptides contain
      rhamnose, fucose, xylose, and galactose, in the ratio 1:1:2:3. A series of
      oligosaccharides was released from the glycopeptides by mild acid hydrolysis,
      while, in contrast, no oligosaccharides were released by either peptide N
      glycosidase F or conventional base-catalyzed beta-elimination and reduction. This
      suggested the presence of a phosphodiester linkage between the carbohydrate and
      peptide, which was further supported by the detection of phosphothreonine in the
      glycopeptides. The mild acid liberated (MAL) fraction was resolved into two major
      acidic oligosaccharides (MAL-P1 and MAL-P2), two minor neutral oligosaccharides
      (MAL-P1b and MAL-P2b) and a neutral fraction (MAL-N1), consisting of Gal and Xyl
      monosaccharides. The MAL-P1 and MAL-P2 oligosaccharides proved to be hexa- and
      hepta-saccharides that shared a common xylose reducing terminus, but differed by
      one galactofuranose residue, and their negative charge was shown to be due to the
      presence of cyclic-phosphate attached to nonreducing terminal galactofuranose
      residues. The MAL-P1b and MAL-P2b oligosaccharides appeared to be
      nonphosphorylated versions of MAL-P1 and MAL-P2. Partial structures of MAL-P1 and
      MAL-P2 are suggested, based on compositional analyses, electrospray mass
      spectrometry, and tandem mass spectrometry before and after permethylation. The
      origin and significance of these unique trypanosomatid glycoconjugates is
      discussed.

PMID- 9023551
TI  - Aggressive angiomyxoma: reappraisal of its relationship to angiomyofibroblastoma
      in a series of 16 cases.
AB  - Aggressive angiomyxoma is a distinctive soft tissue tumor associated with a high
      risk of local recurrence but lacks metastatic potential. This tumour occurs
      nearly exclusively in the soft tissues of the pelvis and perineum of adult women.
      The line of differentiation is not firmly established, but a
      fibroblastic/myofibroblastic origin has been proposed. We report 16 new cases of
      aggressive angiomyxoma of the pelvic soft tissue in women. In all cases bundles
      of cells, most often adjacent to vessels, with histological features of smooth
      muscle cells were identified. In 11 of 14 cases the myoid bundles were
      immunoreactive for desmin; they were also positive for smooth muscle actin in 10
      of 11 cases. In 13 of 14 cases lesional stromal cells showed immunoreactivity for
      desmin. Three cases showed areas with histological features similar to those of
      angiomyofibroblastoma of the vulva, thus representing previously undescribed
      morphological overlap between these two entities. We conclude that aggressive
      angiomyxoma and angiomyofibroblastoma are related neoplasms in a spectrum of
      tumours showing myofibroblastic origin. Furthermore, the demonstration of
      immunoreactivity for desmin in aggressive angiomyxomas implies that this antibody
      is not helpful in discriminating between these two tumours, and the principal
      means of distinction remains histomorphological analysis.

PMID- 9023552
TI  - The endometrial deficient secretory phase.
AB  - The deficient secretory phase is a functional abnormality of the endometrium that
      has hitherto been poorly recognized. Endometrial curettings form 34 cases were
      examined in detail by histology. We also performed morphometric analyses of
      epithelial cell nuclei and assessed the oestrogen and progesterone receptor
      status of these cases compared with controls. Clinicopathological correlations
      were examined. The cases showing the deficient secretory phase were characterized
      histologically by the presence of elongated, hyperchromatic glandular cell
      nuclei, diminished or no secretory activity in the second half of the menstrual
      cycle and poorly developed stroma. Morphometry confirmed that the nuclei were
      different in shape from those seen at any time during the normal menstrual cycle
      and from basal endometrium. Nuclear expression of oestrogen and progesterone
      receptors in formalin-fixed and paraffin-embedded sections was reduced. It is
      apparent from this study that the endometrial appearances described represent a
      definable condition that may be linked to menstrual irregularities and, in some
      circumstances, infertility; it should be more widely recognized.

PMID- 9023553
TI  - Production and characterization of a new monoclonal antibody effective in
      recognizing the CD3 T-cell associated antigen in formalin-fixed embedded tissue.
AB  - Phenotypic analysis of lymphoproliferative disorders is now considered mandatory
      for accurate classification which is the basis for optimum patient management.
      This is presently carried out in most cases using a range of antibodies
      recognizing B and T-cell antigens effective in paraffin sections, and an antibody
      to CD 3 is currently a key member of such panels, indicating T-cell phenotype.
      Current antibodies to CD3 are polyclonal with the inherent disadvantages of this
      type of reagent compared to monoclonal antibodies. In this study, we have used a
      recombinant fusion protein representing part of the epsilon subunit of the CD3
      molecule to generate a novel monoclonal antibody (NCL-CD3-PS1) effective in
      paraffin sections. The antibody has been characterized biochemically and by
      immunohistochemistry using a wide range of normal and pathological tissues.
      Lineage and phenotype specificity have been supported in our study and results
      from other laboratories are awaited with interest.

PMID- 9023554
TI  - Quantification of immunocompetent cells in testicular germ cell tumours.
AB  - The immunocompetent cells present in the different histological patterns of 43
      testicular germ cell tumours were evaluated. CD3 + and CD45RO + (UCHL1 +) T
      lymphocytes, CD68 + and MAC 387 + macrophages, CD20 + (L26 +) B lymphocytes, and
      kappa and lambda + plasma cells were counted. The number of immunocompetent cells
      per mm2 of tumour tissue, excluding the necrotic areas, was evaluated.
      Microscopic fields were randomly selected by two observers. In order to guarantee
      randomization each surface was divided into parts, numbered through a lattice,
      and some fields were chosen via a random numbers table. This procedure yielded
      significantly different counts from those obtained on subjective selection. The
      number of T-lymphocytes and macrophages was higher in seminomas than in the non
      seminomatous testicular germ cell tumours (P < 0.05) Embryonal carcinomas had
      more T-lymphocytes than immature teratomas. No significant differences were found
      among testicular germ cell tumours with regards to the B-lymphocytes, with the
      exception of the high number of B-lymphocytes in mature teratomas. Kappa + and
      lambda + plasma cells were few in the testicular germ cell tumours. Randomization
      in the quantification of immunocompetent cells in testicular germ cell tumours is
      a good means for evaluation of immune response in all the tumour mass, not only
      in the areas with the most intense inflammatory cell infiltrate, and permits
      comparison of testicular germ cell tumours with other malignant tumours. Study of
      immunocompetent cells in every histological type of testicular germ cell tumour
      is useful in comparing them with other extra-testicular germ cell tumours.

PMID- 9023555
TI  - Activated cytotoxic lymphocytes in lymph nodes from human immunodeficiency virus
      (HIV) 1-infected patients: a light and electronmicroscopic study.
AB  - Persistent generalized lymphadenopathy often develops during HIV-infection. It is
      characterized by follicular hyperplasia which progresses over time to follicular
      involution and finally lymphocyte depletion. To determine whether activated
      cytotoxic T cells (CD8+) are present in the hyperplastic germinal centres, light
      and electronmicroscopic immunogold labelling with monoclonal antibodies were used
      to localize two cytotoxic molecules, perforin and TIA-1. Perforin and TIA-1
      positive cells were detected in the follicles and paracortex of lymph nodes from
      HIV-infected patients, whereas labelling was seen only in cells of the paracortex
      in the hyperplastic lymph nodes from HIV-negative patients. Cytotoxic granules,
      staining positive for perforin and TIA-1, were identified by transmission
      electronmicroscopy, often in proximity to follicular dendritic cells within the
      hyperplastic germinal centres of only HIV-positive patients. These cytotoxic
      cells may play a role in the follicular dendritic cell loss and concomitant
      follicular involution that occur during the evolution of HIV disease.

PMID- 9023556
TI  - Chronic lymphocytic sialoadenitis in HCV-related chronic liver disease:
      comparison of Sjogren's syndrome.
AB  - With the aim of morphologically characterizing chronic sialoadenitis in patients
      with hepatitis C virus (HCV) chronic liver disease, labial salivary gland
      biopsies from 22 chronic HCV liver disease and from 10 primary Sjogren's syndrome
      patients were compared. Only focus score (number of aggregates with more than 50
      lymphocytes per 4 mm2 of glandular tissue) and grading of inflammation were able
      to discriminate significantly between the two patient groups. Duct ectasia,
      acinar depletion, presence of lymphoid aggregates with less than 50 lymphocytes
      and of lymphoid infiltration within intralobular salivary duct epithelium were
      evident in both disease groups and appeared to be non-specific, mostly age
      related changes. In both patient groups plasma cell and lymphocyte typing showed
      similar features: T-lymphocytes represented most of the lymphoid population, B
      lymphocytes were few unless follicles were present. Higher focus score values
      were associated with a plasma cell switch from an IgA to an IgM and/or IgG
      predominance. A greater morphological similarity was seen between biopsies of the
      primary Sjogren's syndrome group and those of female rather than male chronic HCV
      liver disease patients. Salivary gland tissue in HCV patients responds to damage
      in a fashion similar to primary Sjogren's syndrome, the only difference being a
      lesser degree of inflammation.

PMID- 9023557
TI  - Immunohistochemical phenotype of malignant mesothelioma: predictive value of
      CA125 and HBME-1 expression.
AB  - Histological diagnosis of malignant mesothelioma and differentiation from
      adenocarcinoma is often difficult. Definitive pathological confirmation of
      malignant mesothelioma requires demonstration of an appropriate
      immunohistochemical phenotype. Selection of an optimum panel of
      immunohistochemical antibodies for the reliable identification of malignant
      mesothelioma is hindered by the absence of a specific immunohistochemical label
      for mesothelioma cells. Recently, we have found that the ovarian carcinoma cell
      antibody CA125 labels malignant mesothelioma cells, and the antibody HBME-1 has
      been developed as a sensitive mesothelial cell marker. We have compared the
      immunohistochemical staining patterns achieved with CA125 and HBME-1 to those
      obtained using a panel of eight further antibodies in 17 malignant mesotheliomas
      and 14 primary and secondary adenocarcinomas within lung and pleura. CA125
      labelled malignant mesothelioma cells in 15 of 17 cases (88%), and adenocarcinoma
      cells in seven of 14 cases (50%). HBME-1 labelled mesothelioma cells in all 17
      cases (100%) but also labelled adenocarcinoma cells in 10 of 14 cases (71%).
      BerEP4 positively labelled one malignant mesothelioma but was negative in the
      remaining 16 cases and positively labelled nine of 14 adenocarcinomas (64%).
      Monoclonal anti-CEA, AUA-1, CA19.9 and LeuM1 labelled no malignant mesotheliomas
      and were positive in 10 (71%), nine (64%), eight (57%) and six (43%) of 14 cases
      of adenocarcinoma, respectively. Diastase-PAS staining detected neutral mucin in
      none of the malignant mesotheliomas but in 10 (71%) of the 14 adenocarcinomas. We
      conclude that CA125 and HBME-1 do not label mesothelial cells with sufficient
      specificity to be useful for differentiating malignant mesothelioma from
      adenocarcinoma, although negative staining with HBME-1 makes a diagnosis of
      malignant mesothelioma unlikely. As there remains an absence of a specific
      positive mesothelial cell marker this distinction is still most reliably made
      using a panel of antibodies including at least two of the following: anti-CEA,
      AUA-1, BerEP4, LeuM1 and CA19.9, in combination with histochemical assessment of
      neutral mucin production.

PMID- 9023558
TI  - p53-protein and Ki-67-antigen expression are both reliable biomarkers of
      prognosis in thick stage I nodular melanomas of the skin.
AB  - The maximum tumour thickness is the most important prognostic factor in malignant
      melanomas of the skin. However, the clinical outcome of thick nodular melanomas
      remains unpredictable. Therefore, we investigated possible prognostic markers in
      this subset of melanomas. From a melanoma data base, 12 patients with thick (> 3
      mm) stage I nodular melanomas of the skin were identified, who were still without
      signs of progression after five years of follow-up. These tumours were compared
      to randomly selected series of 12 cases, who did not survive the first five years
      after removal of the tumours. We performed immunostaining for the p53-protein and
      the proliferation associated Ki-67-antigen. For quantification of immunostaining
      the tumours were entirely scanned. In addition, all tumours were investigated for
      any differences with conventionally applied prognostic features: the tumour
      thickness: the level of invasion; the prognostic index (tumour thickness
      multiplied by mitotic count); and the mean volume-weighted mean nuclear volume.
      We demonstrated significant differences between survivors and non-survivors
      exclusively in respect of the staining indices for p53 and Ki-67 (P < 0.03 and
      0.02, respectively). With both antibodies the tumours of survivors showed lower
      counts as compared to non-survivors survivors. However, within both groups we
      found no significant correlations between the p53- and Ki-67-staining results. We
      conclude that immunostaining for p53-protein and Ki-67-antigen is helpful to
      identify individuals with thick nodular melanomas who are at risk of metastatic
      disease.

PMID- 9023559
TI  - Clear cell dermatofibroma.
AB  - This series presents six cases of a rare variant of dermatofibroma, characterized
      by marked clear cell change. All lesions occurred on the lower extremities of
      middle-aged adults (four women, two men), mostly with the clinical diagnosis of
      fibrohistiocytic lesion. Histological examination revealed well circumscribed,
      faintly stained dermal to subcutaneous lesions which were due to the overwhelming
      presence of clear cells (> 90%), some with prominent PAS-positive cytoplasmic
      granulation. Overlying epidermal hyperplasia as well as storiform arrangement of
      spindle cells, sclerotic collagen and some interspersed lympho-histiocytic
      infiltrate at the periphery of the lesion indicated the fibrohistiocytic origin.
      Individual histopathological peculiarities included: bizarre giant cells in two
      cases, perifollicular arrangement and haemangiopericytoma-like features with iron
      deposition in one case each. Immunohistochemically three of four lesions showed
      moderate reactivity for factor XIIIa and two of four with an anti-metallothionen
      marker E9, but were otherwise negative with a broad panel of markers.
      Electronmicroscopy in two cases revealed large pools of glycogen beside focal,
      prominent endoplasmic reticulum and lysosomes in some granular cells, but only
      optically translucent cells in cases of clear cells. Recognition of clear cell
      dermatofibroma is important as the differential diagnosis includes some entities
      with more serious outcome/considerations such as metastases of renal cell
      carcinoma, xanthogranulomatous reactions, balloon cell naevus/melanoma and clear
      cell sarcoma.

PMID- 9023560
TI  - Metastatic carcinoma of the prostate presenting as parotid tumour.
AB  - Two patients are described in each of whom metastatic prostatic carcinoma
      presented as a tumour of the parotid gland. In one, primary prostate cancer had
      been diagnosed three years prior to the appearance of what was believed
      clinically to be an unrelated salivary lesion. In the other a neck swelling was
      the first indication of disease, although subsequent investigation revealed
      widespread metastases. Biopsy of each tumour showed an adenocarcinoma with
      immunohistochemical expression of prostate markers. These cases, and the six
      previous reports, illustrate the need to consider metastatic carcinoma from the
      prostate in the assessment of any malignant tumour of the salivary glands in men
      of advancing years.

PMID- 9023561
TI  - Myositis ossificans-like lesion of nerve.
AB  - An unusual ossifying lesion arising within the median nerve of a young adult male
      is presented. While ectopic ossification has been described in a large number of
      sites, intraneural ossification is an uncommon event and usually occurs in
      association with a pre-existing intraneural neoplasm. This case, in contrast,
      bears striking histopathological resemblance to myositis ossificans with
      prominent zonation. We believe that this may represent the first example of a
      benign myositis ossificans-like lesion of nerve.

PMID- 9023562
TI  - Intestinal malakoplakia associated with paracoccidiodomycosis: a new association.

PMID- 9023563
TI  - Papillary mullerian cystadenofibroma of the vagina.

PMID- 9023564
TI  - Histological changes of parathyroid adenoma after percutaneous injection of
      ethanol.

PMID- 9023565
TI  - CD30+ anaplastic large-cell lymphoma, null type, with signet-ring appearance.

PMID- 9023566
TI  - Giant cell angiofibroma of the orbit.

PMID- 9023567
TI  - Smooth muscle tumours of the pleura.

PMID- 9023568
TI  - Cancerization of phyllodes tumour.

PMID- 9023569
TI  - Methylene chloride induced mouse liver and lung tumours: an overview of the role
      of mechanistic studies in human safety assessment.
AB  - B6C3F1 mice exposed to high dose levels of methylene chloride by inhalation for 2
      years had an elevated incidence of liver and lung tumours. These tumours were not
      increased in rats or hamsters exposed under the same or similar conditions. This
      paper gives an overview of research conducted over the last 10 years into the
      mechanism of action of methylene chloride as a mouse carcinogen and into the
      relevance of the mouse data to humans exposed to this chemical. Data are
      presented on the comparative metabolism and pharmacokinetics of methylene
      chloride in mice, rats, hamsters and humans, on the toxicity of methylene
      chloride to the target organs in the mouse, and on the genotoxicity of methylene
      chloride in vitro and in vivo. The enzyme which activates methylene chloride to
      its carcinogenic form has been isolated, sequenced, and cloned, and its
      distribution studied within cells, organs and between species. Evidence has been
      obtained to show the methylene chloride caused cancer in mice as a result of
      interactions between metabolites of the glutathione S-transferase pathway and
      DNA. Damage to mouse lung Clara cells and increased cell division are believed to
      have influenced the development of the lung tumours. The species specificity was
      a direct consequence of the very high activity and specific cellular and nuclear
      localisation of a theta class glutathione S-transferase enzyme which was unique
      to the mouse. Consequently, DNA damage was not detectable in rats in vivo, or in
      hamster and human hepatocytes exposed to cytotoxic dose levels of methylene
      chloride in vitro. These results provide evidence that the mouse is unique in its
      response to methylene chloride and that it is an inappropriate model for human
      health assessment.

PMID- 9023570
TI  - Serotonin syndrome due to venlafaxine and maintenance tranylcypromine therapy.
AB  - A number of novel serotonergic antidepressants have been introduced to clinical
      practice over the last decade. These medications are felt to be safe alternatives
      to the traditional tricyclic antidepressants and monoamine oxidase inhibitors,
      particularly in the overdose setting. Serious adverse reactions and drug
      interactions have been appreciated and fatalities have been reported. We describe
      the development of the serotonin syndrome in a 60 year old female on chronic
      tranylcypromine treatment following the inadvertent ingestion of a single dose of
      venlafaxine. Manifestations included and altered mental status that progressed to
      hyperthermia and coma. She recovered quickly and without complications. Health
      care providers and poison specialists need to be aware that this potentially
      serious syndrome can be precipitated by a single dose of a serotonin reuptake
      inhibitor in patients being treated with a monoamine oxidase inhibitor.

PMID- 9023571
TI  - Effects of pyridostigmine on acetylcholinesterase in different muscles of the
      mouse.
AB  - 1. Pyridostigmine bromide was administered subcutaneously in mice, in a dose of
      4.0 or 2.0 mu moles/kg, and the activity of the predominant (G1, G4 and A12)
      molecular forms of acetylcholinesterase were examined in diaphragm, extensor
      digitorum longus (EDL), and soleus muscles at 3 h, 6 h, 24 h and 5 days. 2. In
      diaphragm, no effect was apparent after the low dose, but after the high dose
      there was a reduction in activity of the functional A12 form at 24 h, followed by
      an increase which had overshot the control level at 5 days. 3. In the fast EDL,
      after the low dose, all three molecular forms were decreased at 3 h but had
      returned to normal by 6 h. This effect was not apparent after the high dose. 4.
      In the slow soleus the low dose caused a significant increase in total enzyme
      activity at 5 days, but the high dose caused significant increases in all
      molecular forms at 3 hours. 5. Thus pyridostigmine had delayed effects on the
      levels of acetylcholinesterase. The three muscles displayed different
      sensitivities to the drug, but the changes were consistent with initial
      inhibition of the activity leading to down-regulation of the enzyme followed by
      up-regulation, which could overshoot the normal levels.

PMID- 9023572
TI  - In vitro drug adsorption to charcoal, silicas, acrylate copolymer and silicone
      oil with charcoal and with acrylate copolymer.
AB  - 1. The relative binding constants of four drugs to charcoal, silicone oil silicas
      and acrylate copolymers was studied using an in-vitro binding technique. 2. The
      maximum adsorption capacity (K2) was chosen as a measure of the degree of binding
      and calculated by fitting to the Langmuir equation. 3. Charcoal alone was shown
      to be the most effective of the adsorbents chosen. The possible use of silicone
      oils as an adsorbent delivery vehicle in treatment of overdose is discussed.

PMID- 9023573
TI  - Rifampicin and isoniazid increase acetaminophen and isoniazid cytotoxicity in
      human HepG2 hepatoma cells.
AB  - Acetaminophen (APAP) induced a concentration-dependent (0-30 mM) cytotoxic effect
      in human HepG2 hepatoma cells which was significantly increased when
      intracellular reduced glutathione (GSH) content was decreased. The cytotoxic
      effect of APAP (0-30 mM) was significantly lower in a day 3-treated compared to
      day 1-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 5 microM 3
      methylcholanthrene (3MC), 50 microM rifampicin (RFP) or 1 mM isoniazid (INH)
      significantly increased 15-30 mM APAP cytotoxicity, of about 15-20% for INH and
      RFP and 35-50% for 3MC. The cytotoxicity of 10 mM APAP was also increased (about
      20%) by a 3-day preincubation with INH but was not affected by 3MC and RFP. INH
      induced a concentration-dependent (0-40 mM) cytotoxic effect in day-1 treated
      HepG2 cells and not significantly affected by decreases in intracellular GSH
      concentrations. INH was not cytotoxic in day 3-treated HepG2 cells. A 3-day
      preincubation of HepG2 cells with 50 mM RFP or 1 mM INH significantly increased
      10-40 mM INH cytotoxicity, respectively of about 10% and 10-25%. A 3-day
      preincubation with 3MC did not modify the cytotoxic effect of INH at these
      concentrations. This is to our knowledge the first report of increases by INH and
      RFP of APAP of INH cytotoxicity in vitro in hepatocellular cells of human origin.
      It is in accordance with clinical observations of severe hepatotoxicity
      associated with APAP or INH usage in patients receiving multiple drug therapy
      (INH, RFP) for tuberculosis or in alcoholics.

PMID- 9023574
TI  - Pharmacokinetics of verapamil in overdose.
AB  - The information on the pharmacokinetics of verapamil in overdose is scanty. We
      report two adults who ingested 3.2 g and 4 g of verapamil, respectively. Both
      patients had hypotension and a severe bradycardia. The highest plasma verapamil
      concentration in these patients was about 2200 ng/ml and 2700 ng/ml,
      respectively. The decline in plasma verapamil and norverapamil concentrations
      followed first-order kinetics, and the half-life of verapamil was 7.8 h and 15.1
      h, respectively. The free fraction of verapamil (non-protein bound) was higher at
      total concentrations exceeding 2000 ng/ml (12-15%) than at lower concentrations
      (2-6%). There seems to be no marked saturation of the metabolism of verapamil in
      acute poisoning. The apparent concentration-dependent changes in the free
      fraction may be due to therapeutic measures.

PMID- 9023575
TI  - Flexibility in the dental curriculum. FDI Working Group.

PMID- 9023576
TI  - Innovative aspects of the 5th year BDS curriculum in Hong Kong.
AB  - In 1990, partially in response to the UK's proposal of a one-year vocational
      training, the BDS course in Hong Kong was extended from four years and one term
      in duration to a full five-years. The 5th year curriculum was intended to be as
      close to vocational training in nature as possible. The Board of
      Multidisciplinary Studies in the BDS 5-Year Curriculum was set up one year prior
      to the implementation of the course. The course was enthusiastically received by
      both students and teaching staff. The most successful and innovative aspects of
      the course included the new Family Practice Clinic, the elective programme where
      all students visited overseas dental institutions and the documentation of cases
      using log books in the final comprehensive examination. A post examination
      questionnaire validated the success of the programme.

PMID- 9023577
TI  - Training examiners for a national epidemiological survey of oral mucosal lesions.
AB  - Ensuring the validity and reliability of data collected in epidemiological
      surveys is an important consideration. The purpose of the present report is to
      describe a training and calibration programme for 16 examiners taking part in a
      national survey of oral mucosal lesions and to present an evaluation of the
      results. The programme included the distribution of a pictorial manual to
      participants and a series of lectures followed by three diagnostic sessions, two
      using slides and the last involving patients. At the final session, the trainees
      classified 88 per cent of 16 patients correctly in comparison with the definitive
      diagnoses of the trainer, and their sensitivity on recording oral carcinoma,
      leukoplakia and lichen planus was at least 0.88. However, correctly classifying
      submucous fibrosis on the basis of slides alone proved problematic. At the
      conclusion, the diagnostic accuracy of two examiners for all types of lesion
      remained appreciably lower than the majority. Training strategies for various
      types of study are discussed. The method reported is considered to represent a
      model approach to training and calibrating examiners for this type of survey
      work.

PMID- 9023578
TI  - Needs, demands and manpower balance. Dentists/populations. FDI Commission, 1996.

PMID- 9023579
TI  - Women as dental patients: are there any gender differences?
AB  - There is an increasing awareness that gender differences affect both health and
      disease. This review looks at gender differences as they pertain to the mouth.
      Not only does pregnancy, the menstrual cycle and the menopause affect the oral
      tissues but there are also gender differences in regard to patterns of dental
      disease as women access dental care differently and react to health promotion in
      a more positive manner. Women live longer and are therefore more likely to be on
      drugs which complicate treatment. Care must also be taken in prescribing drugs
      during pregnancy and lactation and attention must be paid to the interaction of
      drugs with oral contraceptives. Certain systemic diseases such as Sjogrens
      syndrome, rheumatoid arthritis and anorexia nervosa which have specific oral
      manifestations are especially common in women. Although oral cancer is mainly a
      problem among men the rise in smoking among young women poses a problem for the
      future. HIV/AIDS can be diagnosed on the basis of oral lesions and this may be of
      great importance in the event of a pregnancy. Although facial pain and facial
      arthromyalgia (temporomandibular joint dysfunction) pain are common in the
      population, women come forward for treatment much more frequently. Burning
      syndrome is especially common among post menopausal women and urgently needs more
      research.

PMID- 9023580
TI  - Women as leaders.
AB  - The role of women as leaders has undergone considerable review in recent years,
      both outside and within the dental profession. Growing awareness of gender as an
      issue in leadership has focused attention on leadership styles and qualities with
      particular emphasis on the differences between male and female approaches.
      Further research is proposed, specifically on leadership within the dental
      profession. Trends are identified which lead to optimistic conclusions as to the
      future involvement of women in leadership in dentistry.

PMID- 9023581
TI  - Oral rehydration therapy--a dental perspective.
AB  - Sugar-based Oral Rehydration Therapy (ORT) is still the conventional treatment
      for diarrhoeal diseases. The WHO/UNICEF, and other groups endorse and actively
      promote its use for all cases of diarrhoea. Despite the deleterious effects of
      sugars promotion on dental health, and the incontrovertible role of sugars as the
      major factor responsible for the present upsurge in dental caries prevalence in
      the developing countries, the search for an ideal Oral Rehydration Solution (ORS)
      has so far completely ignored any dental considerations. Of the presently
      available rehydration solutions, the cereal or food-based solutions offer greater
      advantages over the sugar based solutions. Further research efforts must be
      directed at non-sugar based ORT, and funding organisations should give support to
      researchers and research institutions working to replace sugars with cereal
      flours, improve food-based ORS, or develop novel approaches to ORT that are based
      on non-cariogenic ingredients. Policy makers, researchers and health care workers
      generally must always consider, in addition to other factors, the dental
      implications of their recommendations on ORT.

PMID- 9023582
TI  - Tooth wear in three ethnic groups in Sabah (northern Borneo).
AB  - The prevalence and associated aetiologies of tooth wear were investigated in
      three ethnic groups in Sabah (Northern Borneo) using the Tooth Wear Index (TWI).
      The number of surfaces with enamel wear only, dentine exposed for less than a
      third or dentine exposed for more than a third were categorised into the TW
      minimal, moderate or severe respectively. A structured questionnaire was used to
      elicit medical/dental history, oral hygiene practices, satisfaction with body
      image, diet and other personal habits/details. The sample comprised of a self
      selected sample of 148 dental hospital attenders; 47 (32 per cent) each of ethnic
      Chinese and Malay and 54 (36 per cent) of ethnic Kadazan, matched for age and
      with a similar number of scoreable teeth per subject. Dentine exposure within the
      total sample was a common finding (95 per cent TW with moderate, 41 per cent TW
      severe). The Kadazan group had significantly (P < 0.05) more surfaces with severe
      tooth wear than the Chinese or Malay. Tobacco chewing was positively associated
      (rho = +0.4, P < 0.05) with both moderate and severe tooth wear, as was the habit
      of crushing/eating bones. Neither carbonated beverages or fresh fruit intake were
      associated with tooth wear, but their frequency of consumption was low. The
      buccal and occlusal surfaces of the posterior teeth were the most severely worn.
      Generally, wear was greater in the upper anterior sextant compared to the lower
      anterior sextant, with the exception of the lower incisal edges in the Kadazan
      group. Tooth wear into dentine was a common occurrence, especially among the
      Kadazan subjects and least among the Chinese subjects. The aetiological factors
      associated with this tooth wear are different to those encountered in Western
      cultures.

PMID- 9023583
TI  - Induction of B cell proliferation and NF-kappa B activation by a water soluble
      glycan from Lentinus lepideus.
AB  - Many immune modulating compounds have been isolated from fungal extracts, but the
      molecular mechanisms of their action have rarely been elucidated. In this study
      we isolated a proteoglycan from cultured mycelia of Lentinus lepideus and tested
      its effects on murine spleen cells. The acidic-polysaccharide fraction was
      obtained by extraction with hot water followed by purification using DEAE
      cellulose anion exchange. The molecular mass of the compound was determined by
      Sepharose CL-4B gel filtration to be approximately 47 kDa. When cultured in the
      presence of the compound, spleen cells from C3H mice underwent rapid cell
      proliferation and cell aggregation. Treatment with the compound also caused a 10
      fold increase in [3H]-thymidine incorporation compared to a control, confirming
      cell proliferation. Flow cytometry analysis indicated that the affected cell
      population was mainly B cells. As one approach to understanding the molecular
      mechanism of this action, we investigated the effects of the compound on cellular
      transcription factors which are known to control the proliferation of immune
      cells. Using gel retardation assays, we found that the compound significantly
      activated NF-kappa B but not AP-1 in spleen cells. Taken together, the data
      suggest that the proteoglycan compound is a biological response modifier that
      stimulates B cell proliferation, probably by regulating cellular transcription
      factors such as NF-kappa B.

PMID- 9023584
TI  - In vivo effects of fluconazole on lymphocyte subpopulations of the thymus and
      spleen in mice: flow cytometry analysis.
AB  - Fluconazole is a triazole compound developed for the therapy of fungal
      infections, especially for systemic fungal infections. In this study 2.5 and 5.0
      mg oral doses of fluconazole per kg of body weight were administered to mice for
      3-28 days, followed by lymphocyte phenotyping by flow cytometry analysis on a
      Becton-Dickinson FACScan. The results show that administration of fluconazole
      neither reduced body and organ weights nor thymocyte and spleen cell count. In
      the thymus and spleen the distribution of all the lymphocyte subpopulations
      studied was unchanged. These results suggest that fluconazole has no in vivo
      effects on the quantity of lymphocyte subpopulations in mice. The results tend to
      support the use of fluconazole in immunosuppressed patients.

PMID- 9023585
TI  - Effect of retinoids on dermal inflammation and on arachidonic acid mobilization
      and metabolism in murine 3T6 fibroblasts retinoids, arachidonate release and
      metabolism.
AB  - Retinoids have shown anti-inflammatory activity in some animal models and human
      diseases, although the mechanism by which retinoids elicit this activity is
      unknown. In this study, retinoids significantly attenuated, in a dose-dependent
      fashion, murine ear oedema induced by phorbol 12-myristate 13-acetate (PMA) or
      oxazolone. Dexamethasone inhibited both oedemas whereas ketoprofen reduced only
      that induced by PMA. PMA application or oxazolone-induced contact
      hypersensitivity markedly increased production of eicosanoids such as 6-keto-PGF1
      alpha or LTB4. The anti-oedematous effects of retinoids were accompanied by
      inhibition of tissue eicosanoid levels. Besides, retinoids showed toxic effects
      on culture fibroblasts caused by an irritant effect on plasma membrane. However,
      when we used subtoxic doses, we demonstrated that retinoids in vitro could
      inhibited arachidonate mobilization and eicosanoid biosynthesis induced in
      fibroblast cultures by PMA, calcium ionophore A23187 or bradykinin. Thus, this
      paper reports the ability of retinoids to inhibit skin inflammatory processes
      induced by tumour promotors or immunological stimuli. Moreover, we have
      demonstrated that retinoids at non-cytotoxic doses may inhibit eicosanoid
      generation and arachidonic acid mobilization in 3T6 fibroblasts.

PMID- 9023586
TI  - The effect of nicotine on murine CD4 T cell responses.
AB  - T cells were exposed to various concentrations of nicotine or smokeless tobacco
      extract (STE) during in vitro immune responses in order to examine effects upon
      expression of T cell costimulatory counter-receptors, CD28 and CTLA-4, and
      cytokine production. Splenic mononuclear cells (SPM) were exposed to 1:10(2) to
      1:10(3) dilutions of STE or 1-100 micrograms/ml nicotine during 48 and 72 h of
      stimulation with anti-CD3. Expression of CD28 and CTLA-4 was evaluated with flow
      cytometry and production and expression of IL-2, IL-4, IL-10 and IFN-gamma were
      evaluated using ELISA and RT-PCR. The data here indicate that the percentage of
      CD4+ T cells expressing CD28 declined while percentage and intensity of CTLA-4
      expression increased with exposure to a 1:10(2) dilution of STE during the T cell
      response. Exposure to nicotine decreased the percentage of CD4+ T cells
      expressing both CD28 and CTLA-4 and decreased the intensity of CD28 expression.
      Responding T cells exposed to nicotine produced significantly less Th1 cytokines,
      IL-2 and IFN-gamma, but significantly more Th2 cytokines, IL-4 and IL-10.
      Cytokine specific mRNA expression was only slightly affected by the exposure to
      nicotine. Thus, exposure of T cells to physiological concentrations of STE or
      nicotine can alter the T cell expression of CD28 and CTLA-4, and the CD4 T cell
      cytokine expression pattern.

PMID- 9023587
TI  - Tumor-derived recognition factor (TDRF) induces production of TNF-alpha by murine
      macrophages, but requires synergy with IFN-gamma alone or in combination with IL
      2 to induce nitric oxide synthase.
AB  - A constitutively produced soluble activity, designated tumor-derived recognition
      factor (TDRF), from L1210, P815 and EL4 tumor targets, was previously shown to
      synergize with interferon-gamma (IFN-gamma) and subactivating concentrations of
      interleukin-2 (IL-2) to induce murine macrophage production of tumor necrosis
      factor-alpha (TNF-alpha) and nitric oxide (NO) for cytotoxicity of the target of
      origin. Another study had suggested that TDRF upregulated both TNF-alpha receptor
      (TNF-alpha R) and IFN-gamma receptor (IFN-gamma R) mRNA synthesis, as well as
      increased TNF-alpha and IFN-gamma binding to their receptors. In the present
      study, we have further characterized the concentration-dependent macrophage
      activating potential of TDRF alone and in synergy with IFN-gamma or IFN-gamma and
      subactivating concentrations of IL-2. Higher concentrations of TDRF acted
      independently on inflammatory C3H FeJ mouse macrophage to induce expression of
      TNF-alpha mRNA and release of TNF-alpha, but failed to induce nitric oxide
      synthase (NOS) mRNA expression and NO generation. At lower concentrations, TDRF
      synergized with either IFN-gamma alone or in combination with IL-2 to stimulate a
      dose-related increase in the expression of TNF-alpha mRNA and secretion of TNF
      alpha, as well as increased induction of NOS mRNA and cytotoxic NO generation by
      macrophage. MCA tumor targets which did not produce TDRF activity were killed by
      macrophage that had been activated by exogenously added L1210-derived TDRF in
      synergy with IFN-gamma or in combination with subactivating concentrations of IL
      2, but not by TDRF alone. Taken together, our results indicate that TDRF acted
      independently in a dose-dependent fashion to induce macrophage synthesis and
      release of TNF-alpha, but in the absence of IFN-gamma or in combination with IL-2
      failed to induce the NOS enzyme which was necessary for cytotoxic NO generation.
      Thus TDRF appears to be a sufficient second signal for IFN-gamma-primed
      macrophage or alternatively a sufficient third signal for IFN-gamma and IL-2
      treated macrophage to culminate the activation process for NOS mRNA synthesis and
      NO-mediated tumor cytotoxicity.

PMID- 9023588
TI  - In vivo indomethacin reverse exercise-induced immunosuppression in rats.
AB  - The effect of oral indomethacin on the immunosuppressive effect of exercise was
      examined in exercised untrained female Wistar rats immunized with sheep red blood
      cell (SRBC) antigens. Intensity of the 1 h exercise was controlled by 0-50 kPa
      air pressure, generated by a compressor located at the bottom of a water tank,
      during continuous swimming of the rats, previously immunized with SRBC. After 48
      72 h, depending on the ip (intraperitoneal) or iv (intravenous) route of SRBC
      immunization, the exercise suppressed humoral PFC response and augmented
      phagocytosis of peritoneum macrophages. These effects occurred only when exercise
      was performed at 48 h after antigen injection. Animals receiving indomethacin,
      however, did not show any exercise-related suppression of the PFC response. The
      data suggest a relationship between exercise-induced immunosuppression and
      possible increased in vivo prostaglandin synthesis during the intense exercise.
      Overall, exercise-related suppression of humoral PFC response was dependent on
      the intensity of the exercise, was time specific, and was reversible by
      pharmacological blockade of the cyclooxygenase pathway of prostaglandin
      synthesis.

PMID- 9023589
TI  - Methimazole inhibits peripheral lymphocyte proliferation by inducing S-quiescent
      phase arrest.
AB  - The influence of methimazole (MTI) on the mitogenic proliferation of human blood
      lymphocytes was studied in vitro to evaluate the potential immunomodulatory
      activity of this antithyroid drug. The effects of the drug on the lymphocyte cell
      cycle were assessed by multiparametric flow cytometry. Although MTI induced an
      increase in the number of lymphocytes in the synthesis and G2M compartments, it
      failed to stimulate proliferation as the cells tended to accumulate in the
      quiescent S compartment. The effect was dose-dependent over a range from 0.1 to
      100 mM. These in vitro results indicate that MTI possesses immunosuppressive
      activity.

PMID- 9023590
TI  - Chagas' disease: enhancement of systemic inflammatory reaction in
      cyclophosphamide treated mice.
AB  - An explanation was sought for the fact that an enhancement of myocarditis occurs
      when Trypanosoma cruzi infected mice is treated with cyclophosphamide (CY).
      Several schedules were tested in mice and two polar models were achieved--one
      presenting parasite exacerbation without inflammatory reaction and the other
      presenting only cellular infiltrate in function of timing and different dosage of
      drug. In those receiving the drug after infection, an enhancement of the parasite
      load was detected and it was associated with an inflammatory reaction when mice
      were treated every other day with low doses of CY (3 mg/kg), but such
      inflammation was not present if a single dose of 200 mg/kg was used 5 days after
      infection. On the other hand, in schedules using 200 mg/kg of CY 2 days before
      infection an enhancement of myocarditis was observed on day 12 post infection,
      but this was not associated with parasite proliferation. Finally when employing a
      single intermediate dose of 40 mg/kg, a parasite load as well as a myocarditis
      enhancement was observed. A correlation between blood monocytes rebound and the
      intensity of myocarditis has been observed, and the varying time of drug
      injection suggested that this cellular infiltrate modulates the parasite load. If
      the immunosuppressive period of the drug occurred during parasite tissue
      invasion, parasite load amplification would occur without myocarditis. This was
      achieved using a single dose (200 mg/kg) of CY five days after infection, since
      monocytosis occurs 7-8 days after drug injection, allowing for parasite
      multiplication in tissues. The present data bring a strong suggestion that the
      modulation of myocarditis and parasite load are directly correlated with the
      leukocytes rebound occurring after the depression period promoted by CY
      treatment.

PMID- 9023591
TI  - Correlation between inhibited alternative complement activity and the protective
      effect induced by Nocardia lysozyme digest (NLD) during Klebsiella pneumoniae
      infection in mice.
AB  - Nocardia lysozyme digest (NLD) was administered intraperitoneally (i.p.) at a
      dose of 500 micrograms/kg to normal and immunosuppressed mice for 3 consecutive
      days prior to inoculation with Klebsiella pneumoniae. A protective effect was
      observed when the pathogen was injected subcutaneously and intravenously, as
      opposed to an aggravating effect obtained in the case of intraperitoneal
      inoculation The i.p. administration of NLD partially restored the
      immunosuppression caused by cyclophosphamide but did not change cobra venom
      induced deterioration of the infection. The results obtained could be regarded as
      a consequence of the lowered alternative pathway serum complement activity and
      the crucial role of the diminished level of complement in the peritoneal cavity.

PMID- 9023592
TI  - An immunotoxicity screening study on salmeterol in rats.
AB  - Salmeterol, a long-acting beta 2-adrenoreceptor agonist without known
      immunotoxicity, was studied in a 28-day repeated dose toxicity test in Wistar
      rats. Several immunotoxicity screening parameters were incorporated in the study
      protocol to investigate the immunotoxic potential of the compound. Male rats were
      orally treated with 0, 0.2, 2 and 20 mg salmeterol/kg body weight/day. At the 20
      mg/kg/day dose level, intubation errors occurred because the animals tried to
      resist intubation. Some of these animals died intercurrently. Therefore, the
      magnitude of the dose was lowered to 10 mg/kg/day at day 9 of treatment. Body
      weight and bone marrow cellularity were not affected. Hematological parameters
      were not altered either, except for platelet counts, that were decreased at all
      dose levels. Also liver weights were decreased at all dose levels tested.
      Absolute thymic weights were decreased at the 2 and 20/10 mg/kg/day dose levels.
      No treatment-related (histo)pathological lesions were seen in the (non)lymphoid
      organs. Serum IgM levels were increased at the 0.2, and IgG at the 2 and 20/10
      mg/kg/day dose levels, respectively. B cell numbers in the spleen were decreased
      at all dose levels tested. The data indicate that the test battery applied to
      salmeterol is able to detect low immunotoxic potential. Further research is
      needed to elucidate whether salmeterol interferes with immune responses in rats
      upon antigenic challenge.

PMID- 9023593
TI  - Achievement of near-normal body weight as the prerequisite to normalize sex
      hormone-binding globulin concentrations in massively obese men.
AB  - OBJECTIVE: To investigate the effects of weight loss on sex hormone-binding
      globulin (SHBG) in massively obese males and whether normal SHBG concentrations
      could be obtained regardless or not of the achievement of normal body weight
      values. DESIGN AND SUBJECTS: Sera were collected for SHBG determination from 63
      massively obese men, partly before they underwent biliopancreatic diversion (pre
      op group = 11) and partly during the post-surgical follow up (post-op group =
      52), and twenty normal weight healthy control men. MEASUREMENTS: Serum SHBG was
      measured using a noncompetitive liquid-phase immunoradiometric assay. RESULTS:
      Baseline general characteristics were similar in both obese groups. Obese
      patients in the post-op group had lost 46.4 +/- 2.9 kg since they had undergone
      operation, namely during a mean period of 14.9 +/- 13.8 (range 1-58) months
      follow up. Obese groups had significantly lower SHBG than normal weight controls
      (66.2 +/- 18.6 nmol/l). However, pre-op obese (19.9 +/- 5.5 nmol/l) had
      significantly lower values than post-op obese subjects (45.5 +/- 24.8 nmol/l; P <
      0.001). There were a highly significant correlation between SHBG and individual
      BMI values (r = -0.629; P < 0.001). Moreover, the post-op obese with BMI values
      lower or equal to 28 had significantly higher SHBG concentrations than those with
      BMI greater than 28 (62.8 +/- 22.2 nmol/l vs 32.1 +/- 19.6 nmol/l; P < 0.001),
      but not significantly different with respect to normal weight controls.
      CONCLUSIONS: Massively obese men weight loss can completely reverse SHBG
      abnormalities, which can be restored to the normal range when near-normal body
      weight is achieved. Since reduced SHBG concentrations can be an independent risk
      factor for the development of diabetes and cardiovascular disease, this
      represents an additional benefit of weight loss program in massively obese
      individuals.

PMID- 9023594
TI  - Deviations from maximum weight predict high-density lipoprotein cholesterol
      levels in runners: the National Runners' Health Study.
AB  - OBJECTIVE: The inverse relationship between adiposity and high-density
      lipoprotein (HDL) cholesterol is well established, however, we believe that its
      usual representation lacks an important dimension. The purpose of this study is
      to test whether the relationship depends upon past weight history in addition to
      current weight. DESIGN: Physician-supplied medical data were compared to
      questionnaires from a national cross-sectional survey. SUBJECTS: 6847 men who ran
      between zero and 171 km per week. MEASUREMENTS: Self-reported current weight,
      greatest lifetime weight and body circumferences were compared to physician
      supplied data for plasma concentrations of HDL cholesterol, low-density
      lipoprotein (LDL) cholesterol, and triglycerides. RESULTS: Current HDL
      cholesterol levels were greatest in those runners with the greatest weight loss
      since their maximum lifetime weight and the greatest reductions in circumference
      of their waist, hip, and chest since their maximum weight. Plasma levels of
      triglycerides, LDL-cholesterol, and total cholesterol/HDL-cholesterol were also
      significantly lower for runners showing the greatest decreases in total and
      regional adiposity since their maximum weight. The results remained significant
      when adjusted for current body mass index and running mileage. CONCLUSION: These
      results suggest that the lipoprotein concentrations of runners are in part
      dependent upon whether the current weight is relatively high or low within the
      historical range of weights experienced by the individual.

PMID- 9023595
TI  - Cognitive effects of a long-term weight reducing diet.
AB  - OBJECTIVE: To investigate if long-term caloric restriction under controlled
      conditions adversely affects cognitive function in obese women. SUBJECTS:
      Healthy, premenopausal women between 23-42 y. Dieting group: n = 14. CONTROL
      GROUP: n = 11. DESIGN: Longitudinal weight loss study (repeated measures within
      subject design) with 3 weeks of baseline, 15 weeks of 50% caloric restriction,
      and 3 weeks of weight stabilization. MEASUREMENTS: Computerized cognitive
      function tests (sustained attention, short-term memory, simple reaction time,
      motor performance and attentional focus), height, body weight, body composition
      (TOBEC) and behavioral questionnaires (Dutch Eating Behaviour Questionnaire,
      Eating Attitudes Test, and State-Trait Anxiety Inventory). RESULTS: Dieting women
      lost 12.3 +/- 5.5 kg (mean +/- s.d.) of body weight. Controlled long-term caloric
      restriction significantly slowed simple reaction time but did not diminish
      sustained attention, motor performance or immediate memory. Word recall
      performance significantly improved by 24% at the end of caloric restriction.
      CONCLUSIONS: The slowing of simple reaction time is a short-term and long-term
      consequence of caloric restriction. In contrast to previous short-term dieting
      studies, sustained attention and immediate memory were not impaired with long
      term caloric restriction.

PMID- 9023596
TI  - VLCD versus LCD in long-term treatment of obesity.
AB  - OBJECTIVE: To compare the long-term effects of three different programs including
      initial 6 weeks (V)LCD diets 420 kcal/d, 530 kcal/d, 880 kcal/d) on sustained
      weight loss, attrition and obesity associated conventional cardiovascular risk
      factors. DESIGN: Prospective, randomized clinical 52 weeks trial. Two weeks of a
      booster (V)LCD period after week 26. SETTING: University outpatient obesity
      clinic. SUBJECTS: Ninety-three middle-aged obese patients (30 men), initial mean
      BMI 38.7 kg/m2, age 20-65 y, from the waiting list. MAIN OUTCOME MEASURES: Weight
      loss pattern, attrition, reported side effects, blood pressure, blood glucose and
      serum lipid levels. Repeated frequent measurements up to week 26, intermittently
      up to final measurements at week 52. RESULTS: One year attrition (30-45%),
      sustained weight loss (8-15% of initial body weight) and changes in obesity
      associated risk parameters were similar in all three group. Fewer adverse events
      were reported in the LCD group. CONCLUSION: The results compare favorably with
      most previous reports of similar design. VLCD (420 kcal or 530 kcal/ d and LCD
      880 kcal/d) were equally effective in long term treatment of obesity. The
      tendency to less side effects with LCD suggests that such preparations deserve
      further attention.

PMID- 9023597
TI  - Maximal secretory capacity of somatotrope cells in obesity: comparison with GH
      deficiency.
AB  - OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in
      obesity and to compare it with that in hypopituitaric patients with GH
      deficiency. DESIGN: Stimulation with GHRH. (1 microgram/kg i.v.), combined with
      arginine (ARG, 0.5 g/kg i.v.), which strongly potentiates the GH response to the
      neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of
      the GH response to GHRH + ARG was evaluated in a second session. SUBJECTS: Forty
      five patients with simple obesity (OB 11 male and 34 female, age 40.5 +/- 1.8 y,
      BMI 38.8 +/- 1.1 kg/m2), 49 patients with hypopituitarism (GHD, 23 male and 26
      female, 43.6 +/- 2.4 y, 24.7 +/- 0.7 kg/m2) and 44 normal young volunteers (NS,
      25 male and 19 female, 33.8 +/- 1.0 y, 21.6 +/- 0.3 kg/m2) were studied.
      MEASUREMENTS: GH levels were assayed by IRMA method, basally at -60 and 0 min,
      and than every 15 min up to +120 min. Basal IGF-I levels were assayed by RIA
      method, after acid-ethanol extraction. RESULTS: IGF-I levels in OB were lower (P
      < 0.005) than those in NS but higher (P < 0.005) than those in GHD. Mean peak GH
      response to GHRH + ARG in OB was clearly lower than that in NS (P < 0.005) and
      higher (P < 0.005) than that in GHD. Sixty-percent OB and 100% GHD showed peak GH
      responses lower than the minimum normal limit in NS (16.5 micrograms/l) while 4%
      OB and only 53% GHD with GH responses lower than 3 micrograms/l, the limit under
      which GH replacement therapy of severe deficiency is allowed. Good
      intraindividual reproducibility of the GH response to GHRH + arginine test was
      present in all groups (OB: r = 0.78, P < 0.0001; GHD: r = 0.57, P < 0.003; NS: r
      = 0.74, P < 0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope
      cells is clearly less than normal in the obese but still more than is seen in GHD
      subjects. However, in about 50% of obese patients, the pituitary GH releasable
      pool overlaps with that of hypopituitaric patients with GH deficiency. Thus, even
      when the maximal secretory capacity of somatotrope cells is evaluated by a potent
      and reproducible provocative tests such as GHRH + arginine, overweight has to be
      taken in a great account as the cause of severely impaired GH response in
      patients with suspected GH deficiency.

PMID- 9023598
TI  - Body fat distribution before and after weight gain in anorexia nervosa.
AB  - OBJECTIVE: To study abdominal fat distribution in anorexia nervosa subjects and
      to assess the effects of initial weight regain on abdominal fat distribution.
      DESIGN: Longitudinal, clinical study. The baseline measurement was acquired
      within four days of admission to the eating disorders clinic. All patients were
      treated by re-feeding, reinforced by psychotherapy. Following weight regain of at
      least 5 kg, a second body fat distribution evaluation was performed. Of the 21
      subjects evaluated at baseline, 14 achieved the goal of body weight regain and
      were retested. PATIENTS: Fourteen subjects (age: 18-38 y; body mass index: 11.5
      18.3; relative body weight: 54.9-88.3%). MEASUREMENTS: Total, subcutaneous and
      visceral abdominal adipose tissue areas at the L4-L5 level were evaluated by
      computed tomography. RESULTS: At baseline the subjects showed a higher proportion
      of visceral adipose tissue (% visceral adipose tissue = 55.3 +/- 26.1). A
      significant association was observed between body weight and both subcutaneous
      adipose tissue and total adipose tissue. A regain of body weight of 7.3 +/- 1.6
      kg was accompanied by a significant increase in total adipose tissue, comprising
      both subcutaneous and visceral adipose tissue. The increase observed in
      subcutaneous adipose tissue, however, was significantly greater than for visceral
      adipose tissue (212.6% vs 116.8%, respectively, P < 0.01). CONCLUSION: The
      results of the current study show a higher proportion of visceral adipose tissue
      than subcutaneous adipose tissue in anorexia nervosa subjects. With regain of
      body weight there is a preferential regain of subcutaneous adipose tissue. These
      data demonstrate a redistribution of abdominal adipose tissue with weight regain
      in anorexia nervosa subjects.

PMID- 9023599
TI  - The effect of sucrose- and aspartame-sweetened drinks on energy intake, hunger
      and food choice of female, moderately restrained eaters.
AB  - OBJECTIVE: To compare the effects of aspartame-sweetened and sucrose-sweetened
      soft drinks on food intake and appetite ratings of female restrained eaters.
      SUBJECTS: Fourteen female students, shown to have eating restraint. METHODS:
      Subjects were given four drinks (330 ml) of aspartame-sweetened lemonade, sucrose
      sweetened lemonade and carbonated mineral water on three separate days. Seven of
      the subjects were informed of the drink type they were consuming on each
      occasion. MEASUREMENTS: Appetite ratings were recorded and energy and
      macronutrient intakes were measured during the study day and day after leaving
      the department. RESULTS: During the first study day energy intake was lower
      whilst drinking the sucrose-sweetened lemonade compared with the aspartame
      sweetened lemonade, although neither differed significantly from energy intakes
      during the day the drank water. When the calories from the sucrose-sweetened
      lemonade were included (1381 kJ, 330 Kcal) energy intake did not differ between
      treatments. The following day energy intake was significantly higher after the
      aspartame-sweetened lemonade compared with both sucrose-sweetened lemonade and
      the water due to an increase in the amount of carbohydrate consumed and resulted
      in a higher total energy intake over the two days studied. Knowledge of the drink
      types had no effect on energy intake or macronutrient intake. Appetite ratings
      did not differ between drinks and were not affected by knowledge of the drink
      types. CONCLUSION: These results suggest that in females with eating restraint,
      substituting sucrose-sweetened drinks for diet drinks does not reduce total
      energy intake and may even result in a higher intake during the subsequent day.

PMID- 9023600
TI  - Coronary atherosclerosis and myocardial hypertrophy in relation to body fat
      distribution in healthy women: an autopsy study on 33 violent deaths.
AB  - OBJECTIVE: To determine the relationship between cardiovascular pathology and
      body fat distribution in healthy women with no ante mortem clinical evidence of
      cardiovascular disease. SUBJECTS: Thirty-three female forensic autopsy cases of
      sudden death from violent causes. METHODS: Body height and weight, the
      circumferences of the waist and hip and the thicknesses of the subscapular and
      abdominal subcutaneous fat were measured, and Body Mass Index (BMI) and Waist-to
      Hip ratio (WHR) were calculated. Omental, mesenterial and perirenal fat deposits
      were weighted. Heart weight was indexed to height (2.7), the degree of coronary
      narrowing was determined in each artery, and myocardial collagen volume fraction
      and myocyte cross-sectional area were measured. RESULTS: The degree of coronary
      narrowing, heart weight in absolute terms and indexed to height (2.7), myocyte
      cross-sectional area and all the measures of obesity were significantly
      positively correlated with age. Regression of coronary narrowing on measures of
      obesity indicated that a quadratic model fitted the data for BMI, waist
      circumference and intra-abdominal fat better than a linear one. After adjusting
      for age, the degree of coronary narrowing was related to tertiles of BMI, waist
      circumference, WHR and intra-abdominal fat, the severity of the narrowing being
      most marked in the second tertile of BMI (24.0-31.0), waist circumference (80-96
      cm) and intra-abdominal fat (500-1700 g), but in the third tertile of WHR (over
      0.92). Regression on heart weight/height (2.7) on the aforementioned measures of
      obesity indicated a clearly linear association and heart weight indexed to height
      (2.7) was related to tertiles of BMI, waist circumference and WHR, and also to
      tertiles of intra-abdominal fat. CONCLUSIONS: The results suggest that body
      fatness and abdominal accumulation of fat are associated with the severity of
      coronary atherosclerosis and myocardial hypertrophy in women with no clinical
      evidence of cardiovascular disease, but the relationship between coronary lesions
      and BMI is not linear. Both coronary lesions and myocardial hypertrophy are more
      advanced as the numerical value for WHR increases in women. Future autopsy
      studies should be directed at young women with increased WHR in order to
      determine their risk of developing life-threatening lesions in the
      atherosclerosis-prone regions of the coronary tree.

PMID- 9023601
TI  - Is leptin sensitivity the link between smoking cessation and weight gain?
AB  - The known association between smoking cessation and weight gain, and the
      suggested role of leptin in the control of body weight, led to the present study
      which examined the association between smoking and serum leptin concentrations.
      Mean serum leptin levels, independent of body mass index (BMI), were calculated
      in male smokers and non-smokers from Nauru, Western Samoa and Mauritius. Smokers
      were generally leaner than non-smokers, and of similar ages. Levels of physical
      activity and glucose tolerance status were similar for smokers and non-smokers in
      Nauru and Western Samoa, while in Mauritius smokers were more active and less
      likely to be diabetic. Leptin concentrations in smokers were significantly lower
      than in non-smokers, even after adjusting for BMI, waist/hip ratio (WHR) or waist
      girth (P < or = 0.04). This association was independent of diabetes status.
      Smoking, via nicotinic mechanisms, may modify the sensitivity of hypothalamic
      leptin receptors and consequently modulate leptin synthesis and reduce body
      weight.

PMID- 9023602
TI  - Dieting, weight and health in adolescents in The Netherlands.
AB  - OBJECTIVE: To estimate the prevalence of dieting and the relationship between
      dieting, nutritional habits, and health among young adolescents in the
      Netherlands. METHODS: Out of 1359 secondary school children, aged 13 through 15
      y, who were invited for a routine health assessment by school doctors or nurses
      as part of the Child Health Monitoring System, 1279 (94%) responded and data were
      analyzed. RESULTS: Among secondary school children 13% of girls and 5% of boys
      were dieting at the time of the health assessment. Half of the dieting pupils
      were at risk of overweight, while the other half were within the normal weight
      range. The mean preferred weight of the dieting pupils was not lower than the
      mean actual weight of the non-dieting pupils. Dieting pupils skipped meals more
      often and consumed less sweets and salty snacks, soft drinks and bread than non
      dieting pupils. School absence due to illness was relatively high in dieting
      boys, and medicine use was high in dieting girls. CONCLUSION: As in other Western
      countries, dieting is a common practise among young adolescents in the
      Netherlands, especially in girls. "Unhealthy' dietary practices, like skipping
      breakfast, are already present at early age, therefore preventive programs should
      be targeted at young adolescents.

PMID- 9023603
TI  - Nutritional status in adults in the pluri-ethnic population of New Caledonia. The
      CALDIA Study Group.
AB  - OBJECTIVE: To describe the nutritional status (body mass index (BMI) and waist
      hip ratio (WHR)) of the population of New Caledonia in relation to ethnicity and
      urban-rural environment. DESIGN: Diabetes screening survey in two rural provinces
      of New Caledonia and in the suburbs of Noumea. SUBJECTS: 8875 subjects aged 30-59
      y, Europeans, Melanesians and Polynesians. MEASUREMENTS: BMI, WHR. RESULTS:
      Obesity (BMI > or = 27 kg/m2 in men, 25 kg/m2 in women) was highly prevalent in
      all groups, but varied according to ethnicity: respectively, 43% and 52% in
      Europeans, 46% and 72% in Melanesians, 72% and 83% in Polynesians. In the urban
      area, mean WHR values, adjusted for age and BMI, were significantly higher than
      in rural areas, especially in Melanesians. CONCLUSION: Both ethnicity and urban
      rural environment are linked to the amount and distribution of adiposity, which
      appeared worsened in the urban area in Europeans, and even more in Melanesians.

PMID- 9023604
TI  - Accuracy of 1-, 5- and 10-year body weight recall given in a standard
      questionnaire.
AB  - OBJECTIVE: Estimation of the accuracy of 1, 5 and 10 y body weight recall.
      DESIGN: Comparison of information on body weight history from a patient
      questionnaire with measured body weights retrieved in general practitioners'
      records. SUBJECTS: Among 729 newly diagnosed diabetic patients record information
      on measured body weight was found for 86, 141 and 122 patients recalling their
      body weight 1,5 and 10 y ago, respectively. Median age was 63.6 y. Median body
      mass index was 31.1 kg/m2. RESULTS: No average deviation between 1 y body weight
      recall and the corresponding measured weights is observed, but 5 and 10 y recall
      underestimates the measured weights by 1.89 kg and 1.98 kg on an average,
      respectively. On the individual level the agreement is less satisfactory with
      increasing variability the further back in time you go. The recall does not vary
      with age and sex and it is independent of weight status, marital status, smoking
      habits and self-reported health status in this obese group of individuals.
      CONCLUSIONS: The findings suggest that data from three standard questions may
      contribute with useful information on near weight history, independent of age,
      sex and current body weight.

PMID- 9023605
TI  - Plasma lipids, dehydroepiandosterone sulphate and insulin concentrations in
      elderly overweight angina patients, and effect of weight loss.
AB  - OBJECTIVE: To investigate the effect of moderate weight loss in older overweight
      subjects with angina pectoris on plasma dehydroepiandosterone sulphate (DHEAS),
      urinary steroid metabolites, insulin and plasma lipid concentrations. DESIGN:
      Single stranded study of dietitian led dietary intervention for weight loss in a
      volunteer outpatient group of 41 subjects with angina (22 males, 19 females), BMI
      29.1 s.d. 4.2 kg/m2 aged 61.3 s.d. 6.5 y. MEASUREMENTS: Body weight and
      composition by anthropometry, REE by indirect calorimetry, dietary intake by
      seven day inventory, plasma DHEAS, insulin and lipids. RESULTS: After 12 weeks
      dietary supervision there were reductions in body weight (3.3 s.d. 2.3 kg, BMI
      1.2 s.d., P = 0.00001) and in reported energy intake (-1179 s.d. 1393 kJ daily, P
      = 0.0001. No significant change was seen in plasma DHEAS or insulin but there
      were reductions in plasma cholesterol (-0.5 s.d. 0.6 mmol/l, P = 0.0001) HDL
      cholesterol (-0.1 s.d. 0.1 mmol/l, P = 0.0048) and triglyceride (-0.1 mmol/l s.d.
      0.5, P = 0.055). CONCLUSION: Weight loss of 4% body weight by conventional
      dietary means over 12 weeks does not alter plasma DHEAS, urinary steroid
      metabolites or insulin concentrations, but does reduce plasma cholesterol in
      older moderately overweight subjects with angina.

PMID- 9023607
TI  - The influences of height and age on waist circumference as an index of adiposity
      in adults.
AB  - OBJECTIVES: To assess the influences of height and age on the differences in
      waist circumference between individuals of different stature. SUBJECTS: 3319
      males and 4358 females from four studies in the UK and the Netherlands.
      MEASUREMENTS: Waist circumference, body weight, height, and age. RESULTS: Linear
      regression analysis of log10 height as the independent variable on log10 waist as
      the dependent variable was used to determine the optimal index powers (OIP) (p)
      to minimize the influence of height in the relationships of waist/height(p). Six
      out of eight samples of men and women had OIP of height not significantly
      different from zero, with the remaining two groups had OIP between 0.15-0.58,
      indicating that height had very limited influence on the differences in waist
      circumference measurement between individuals. Age adjustment increased the
      relationship between waist and height, with OIP of 0.19-0.89 in men and 0.02-0.58
      in women. Without age adjustment, height explained 0.3-3.5% and 0.1-2.5% variance
      in waist in men and in women respectively, and the corresponding variances were
      0.4-7.5% in men and 0.0-2.6% in women with age adjustment. A similar analysis of
      weight and height showed the OIP of height in weight/height(p) ratio ranged from
      1.32-2.25 in men, and 0.87-1.74 in women without age adjustment, and from 1.47
      2.24 in men and 1.25-1.96 in women with age adjustment. CONCLUSION: Height and
      age had limited influences on the differences in waist between Caucasian subjects
      of different stature. Waist alone may be used to indicate adiposity or to reflect
      metabolic risk factors. In contrast, the influence of height on body weight is
      important.

PMID- 9023606
TI  - Lipolysis in human fat cells obtained under local and general anesthesia.
AB  - OBJECTIVES: As adipose tissue is usually obtained during local or general
      anesthesia in clinical studies, these two forms of anesthesia were presently
      compared as regards lipolysis induced by catecholamines in isolated human fat
      cells. DESIGN: Fat samples from the abdominal subcutaneous region were obtained
      first during local anesthesia (lidocaine) given so that the anesthetic agent did
      not influence lipolysis and second, during gastric banding under general
      anesthesia (propofol) immediately after skin incision. SUBJECTS: Eleven obese
      patients, drug free and otherwise healthy. MEASUREMENTS: Isolated fat cells were
      incubated in the presence or absence of increasing concentrations of different
      lipolysis agents, acting at adrenoceptor or various post-receptor levels in the
      lipolytic cascade. Glycerol release to the incubation medium was measured as an
      index of lipolysis. RESULTS: All agonists caused a concentration dependent
      increase (terbutaline, dobutamine, CGP 12177, forskolin, dibutyryl cyclic AMP,
      isoprenaline and noradrenaline) or inhibition (clonidine) of glycerol release.
      The comparison of data from local and general anesthesia procedures showed no
      statistical difference in glycerol response for any of the drugs used.
      CONCLUSIONS: Adrenergic regulation of lipolysis is not influenced by the mode of
      sampling, at least not in subcutaneous fat cells of obese subjects obtained
      during local anesthesia with lidocaine as compared to general anesthesia with
      propofol.

PMID- 9023608
TI  - Psychiatry's culture.
AB  - Culture remains an ambiguous concept for psychiatry: deprecated by the assumption
      that it is secondary to biomedical reality, yet at the same time some notion of
      'culture' has served to represent the modern against the primitive. Contemporary
      clinical understandings of culture derive from imperial medicine which had
      applied the accepted distinction between the biological form and the cultural
      content of psychopathology to local illnesses which could not easily be fitted
      into the European nosology. The later concept of culture-bound pathology, like
      the psychoanalysts' 'modal personality', only imperfectly escaped from evaluative
      assumptions of 'development', but it is difficult to argue that psychiatry
      provided British colonial administrations with any significant ideological
      justification.

PMID- 9023610
TI  - Child abuse: a universal 'diagnostic' category? The implication of culture in
      definition and assessment.
AB  - The professionalisation of the care and protection of children in the West has
      resulted from a complex of events that are particular to Europe, and that reflect
      Western cultural beliefs about the self, subjective experience and interpersonal
      connections. Attempts to universalise Western definitions of 'child abuse' fail
      to take into account the cultural and social realities of 'non-Western' children
      and families. Clinical material is presented from two South Asian families in
      Britain, and attributions of meaning by Western professionals and the South Asian
      family are discussed.

PMID- 9023609
TI  - The cultural origins of western depression.
AB  - Focusing on the British cultural vocabulary of guilt, fatigue, energy, stress and
      depression; this paper argues that such vocabularies have their own unique
      histories and meanings; deeply embedded, in this instance, within "white British
      and western European" institutions. Predicated on a western epistemology, these
      constructs developed in response to prevailing concerns at different periods in
      western history; but are now assumed to be universal natural entities that await
      further scientific research and investigation. The cross-cultural validity of
      depression as a universal disorder is therefore dubious and needs an extensive re
      examination.

PMID- 9023611
TI  - From PTSD to voices in context: from an "experience-far" to an "experience-near"
      understanding of responses to war and atrocity across cultures.
AB  - This paper examines some of the difficulties of exporting the Western concept of
      Post Traumatic Stress Disorder (PTSD) to non-Western cultures. Using data drawn
      from Guatemala where I lived and worked among Quiche Mayan war widows,
      illustrates how culturally-specific understandings of events and reactions to
      them affect the well-being (or otherwise) of people exposed to extreme adverse
      events. The paper turns to the voices of the widows, who experienced and survived
      intense political conflict, explaining their experiences of violence within their
      particular context.

PMID- 9023612
TI  - Clinical examples of cross-cultural work in a community learning disability
      service.
AB  - The debate on the correct application of the terms race and ethnicity continues
      while community care takes place in a multicultural society. The impact of mental
      illness and mental handicap (currently referred to as learning disability) on
      different ethnic groups partly depends on societal influences which also
      determine the policy for service organisation. As the treatment and support of
      the mentally handicapped has moved away from the custodial care of yesteryear,
      professionals must ensure that their practice is sensitive to the religion,
      ethnicity and languages of the communities they serve. This paper describes
      examples of psychiatric clinical practice with two families of Greek and Kuwaiti
      background, in the setting of a community learning disability team.

PMID- 9023613
TI  - Thrombolysis after acute myocardial infarction.
AB  - Appropriate use of a thrombolytic agent may save 20 to 30 lives per 1000
      treatments. Thrombolysis should be considered in all patients presenting with
      cardiac chest pain lasting more than 30 minutes for up to 12 hours after symptom
      onset. ECG criteria include ST elevation of at least 1 mm in limb leads and/or at
      least 2 mm in two or more adjacent chest leads or left bundle branch block. There
      is no upper age limit. All patients should also receive oral aspirin and
      subcutaneous (intravenous with rt-PA) heparin. Other adjuvant treatments have
      been reviewed previously in this journal. Streptokinase is the drug of choice
      except where there is persistent hypotension, previous streptokinase or APSAC at
      any time, known allergy to streptokinase, or a recent proven streptococcal
      infection. In these circumstances the patient should receive rt-PA. Additional
      indications for rt-PA, based on subset analysis by the GUSTO investigators,
      include patients with ALL of the following: age less than 75 years, presentation
      within four hours of symptom onset, and ECG evidence of anterior acute myocardial
      infarction. Treatment should be initiated as soon as possible. The greatest
      benefit is observed in patients treated early, pain to treat intervals of less
      than one hour make possible mortality reductions of nearly 50%. "When" matters
      more than "where": fast tracking to the CCU is one option but A&E initiated
      thrombolysis is feasible and timely. Prehospital thrombolysis is appropriate in
      certain geographical situations. The development of practical guidelines for
      thrombolysis represents the most comprehensive example of evidence based
      medicine. Streptokinase was first shown to influence outcome in acute myocardial
      infarction nearly 40 years ago. More recently alternative regimes have been
      evaluated in several prospective randomised controlled trials yielding pooled
      data on nearly 60,000 patients. However, systematic review of cumulative data
      reveals a statistically significant mortality gain for intravenous streptokinase
      over placebo which could have been identified as early as 1971-at least 15 years
      before it became generally used in clinical practice.

PMID- 9023614
TI  - Initial assessment and outcome of head injured patients transferred to a regional
      neurosurgical service: what do we miss?
AB  - OBJECTIVE: To assess the level of missed extracranial injuries in patients
      transferred to a regional neurosurgical service for ongoing head injury
      management. METHODS: A three year prospective study conducted under the auspices
      of the Scottish Trauma Audit Group. All patients were followed during their
      hospital stay by independent audit staff, their injuries being recorded and
      scored using established criteria. RESULTS: 115 head trauma patients were
      transferred during the study period. 15 patients died (13% mortality). Eight of a
      total of 87 separate, scorable extracranial injuries were missed (error rate 9%),
      none of which was serious. There were no missed injuries in patients who died.
      77% of patients were managed by an accident and emergency doctor of at least
      registrar grade. CONCLUSIONS: In contrast to other published series, this study
      has shown a low rate of missed extracranial injuries in a group of patients whose
      initial assessment is notoriously difficult. Early involvement by an experienced
      accident and emergency doctor may play an important part in the overall
      management of such patients.

PMID- 9023615
TI  - Radiography for head trauma in children: what guidelines should we use?
AB  - OBJECTIVE: To audit the appropriateness of skill radiography in children
      attending an accident and emergency (A&E) department with head injuries. METHODS:
      569 children presenting to a large teaching hospital A&E unit were
      retrospectively audited. The indications for radiography according to British
      published guidelines and American published guidelines were compared with the
      actual requests for radiography. The criteria for admission from the two
      guidelines were also compared with the actual admissions. RESULTS: 50% of
      children presenting with head injury actually had skull radiography. If British
      guidelines for the use of skull radiography had been complied with, 63% of
      children should have had radiography, but if American guidelines had been used,
      18% would have required radiography. All the actual fractures identified were in
      this 18%. CONCLUSIONS: The British guidelines overinvestigate children with head
      injury. This seems to have been recognised clinically, and the doctors did not
      adhere to the guidelines. Neither did they adhere to the American guidelines,
      which would have resulted in a further reduction in radiography. All the
      fractures identified were covered by the American guidelines. The American
      guidelines for skull radiography can be safely used in a British A&E unit.

PMID- 9023616
TI  - A national census of those attending UK accident and emergency departments with
      asthma. The UK National Asthma Task Force.
AB  - OBJECTIVE: To obtain a representative national picture of the type of people with
      asthma attending accident and emergency (A&E) departments in the UK, the reasons
      why they attend, and to determine the proportion admitted to hospital. DESIGN: A
      national census involving questionnaires. SETTING: 100 A&E departments throughout
      the UK. SUBJECTS: All those with asthma attending because of asthma during a one
      week period in September 1994. RESULTS: Details were obtained about 1292
      attendances. About half of all attendances were by adults and half by children,
      and 87.8% were previously diagnosed asthmatics; 18.8% of adult attenders were
      unemployed. Perceived severity of asthma was the reason for attendance in 65.5%,
      but 11.5% reported non-availability, or perceived non-availability, of the
      general practitioner (GP) as the reason for attending. One fifth of adults had
      been kept awake by their asthma for over three nights before attendance. 425 of
      the 1292 attenders (32.9%) had been admitted to hospital in the previous 12
      months and 316 (24.5%) had attended the A&E department in the previous three
      months. Only 24.6% of attenders had had contact with their general practitioner
      in the previous 24 h. 61.6% of under-5 attenders (n = 341) were admitted to
      hospital; the figures for those aged 5-15 and 15+ years and above were 265
      (41.4%) and 665 (38.7%). CONCLUSIONS: Many people with asthma attend A&E
      departments without first having seen their GP. In many adult cases the asthma,
      while severe, is not acute, but a high proportion of both adults and children are
      admitted to hospital. Many of these attendances and admissions are repeat
      attendances. To enhance the quality of care provided to those with asthma may
      require easier access to primary care, enhanced patient education, or enhanced
      health professional education. Further study is needed of a variety of potential
      interventions.

PMID- 9023617
TI  - Patients telephoning A&E for advice: a comparison of expectations and outcomes.
AB  - OBJECTIVE: To investigate the expectations of patients when they phone the
      accident and emergency (A&E) department, how this relates to the advice they
      receive, the action they subsequently take, and their satisfaction with the
      service. SETTING: The study was undertaken at an inner city hospital in south
      east London. METHODS: 597 calls to the department were documented during the
      study period, and callers for whom a phone number had been recorded were followed
      up by structured interviews carried out by a trained interviewer within 72 h of
      the call. Up to three attempts were made to contact each patient. The interviews
      were conducted at various times of the day to avoid excluding people with
      different work or social patterns. RESULTS: The interviewer was able to contact
      203 patients within 72 h of their call to the A&E department. Of these 197 (97%)
      agreed to participate. Almost two thirds stated that when they phoned A&E they
      anticipated receiving self care advice; 11% expected to be advised to see or
      contact their general practitioner. Only a quarter of callers stated that they
      had expected to be told to attend A&E. There was disagreement between the advice
      that nurses documented as having been given, the advice the caller recalled
      receiving, and the action the patient subsequently took. Even so, 107 (55%)
      callers were very satisfied and 62 (32%) were satisfied, while 11 (6%) were
      dissatisfied with the telephone consultation; 15 (8%) were unsure. In all, 170
      (87%) thought the advice they received was helpful. CONCLUSIONS: Understanding
      the reasons why patients phone A&E departments and their expectations should
      contribute to developing more responsive and effective services.

PMID- 9023618
TI  - Organ donation in the accident and emergency department: a study of relatives'
      views.
AB  - OBJECTIVE: To determine whether recently bereaved people would object to being
      asked about organ donation immediately after the death of their relative.
      METHODS: A telephone interview of 78 recently bereaved relatives of people who
      had died in an inner city accident and emergency (A&E) department; 68 (87%)
      agreed to participate in the study and were sent a questionnaire. Outcome
      measures were views on being asked about organ donation in the A&E department
      immediately after the death of a relative and knowledge of the possibility for
      organ donation in A&E after a sudden death. RESULTS: 37 questionnaires were
      returned: 27 (72.9%) of those who responded would not have minded being asked,
      five would have minded, and five did not know or did not fill in the
      questionnaire; 29 were aware that organs could be donated following a death in
      A&E. Only six people had discussed organ donation before the bereavement. Only
      two of the people who died and seven of their relatives carried a donor card.
      Sixteen had heard about the NHS donor register. CONCLUSIONS: Most those
      responding would not have minded being asked about organ donation following a
      sudden death. More education is needed in two main areas: (1) to raise public
      awareness about the shortage of donor organs; (2) to improve the medical and
      nursing confidence in discussing these difficult issues sensitively but more
      openly and frequently.

PMID- 9023619
TI  - Cardiopulmonary arrest in general wards: a retrospective study of referral
      patterns to an intensive care facility and their influence on outcome.
AB  - OBJECTIVE: To analyse the effect on outcome of referral to specialist facilities
      after cardiopulmonary arrest in a general ward. METHODS: A retrospective analysis
      of resuscitation records of 743 patients in whom cardiopulmonary resuscitation
      was performed in a general ward between 1988 and 1992. After successful initial
      cardiopulmonary resuscitation, patients were identified as transferred to
      coronary care unit (CCU) or intensive care unit (ITU), or as staying in a general
      ward. MAIN OUTCOME MEASURE: Survival to discharge home. RESULTS: There were 322
      initial survivors, of whom 148 (20% of the overall total) survived to be
      discharged from hospital; 63% of those transferred to CCU and 48% of those
      transferred to ITU survived to discharge, compared with 28% of those who stayed
      on the ward (P < 0.001). Of those aged less than 65 years, 75% survived to
      discharge after transfer to CCU and 54% after transfer to ITU, compared with 44%
      of those who stayed on the ward (P = 0.023); the respective figures for those
      over 65 years were: CCU 25%, ITU 34%, ward 25% (P = 0.014). Only half of those
      aged more than 65 years were transferred to a specialist facility, compared with
      90% of those aged less than 65. CONCLUSIONS: Transfer to a specialist care
      facility after resuscitation from cardiopulmonary arrest has an influence on
      outcome. Age as an independent factor is not an appropriate criterion to use in
      deciding on transfer. The decision to arrange transfer must always be taken by
      the most experienced person available, and in line with peer reviewed guidelines.

PMID- 9023620
TI  - A comparison of glucagon and glucose in prehospital hypoglycaemia.
AB  - OBJECTIVE: To compare intramuscular glucagon with intravenous glucose in the
      prehospital management of hypoglycaemia in adults. METHODS: In the first part of
      the trial all UK ambulance services were asked how their personnel treat
      prehospital episodes of hypoglycaemia. In the second part, two protocols for
      treating prehospital hypoglycaemia were studied. In phase 1, intramuscular
      glucagon 1 mg was used. In phase 2, intravenous glucose 25 g was used; if
      intravenous access was not possible, intramuscular glucagon was given. RESULTS:
      33 out of 43 respondent ambulance services (76.7%) only use glucagon for
      prehospital hypoglycaemia; the remaining services use glucose and glucagon. In
      the second part of the study the median duration from diagnosis to full
      orientation (Glasgow coma score 15) was 28 minutes (95% confidence interval 18 to
      49 minutes) in phase 1 and 11 minutes (95% confidence interval 8 to 19 minutes)
      in phase 2. This difference is statistically significant (P < 0.005). On-scene
      times were not significantly different. CONCLUSIONS: Intravenous glucose is the
      treatment of choice in prehospital hypoglycaemia but glucagon should also be
      available for intramuscular use when intravenous access is not possible.

PMID- 9023621
TI  - Titrated intravenous opioids from the same syringe: an infection risk?
AB  - OBJECTIVE: (1) To compare the rate of contamination of syringes prepared under
      laminar flow conditions in pharmacy with those prepared by nurses in the
      emergency department; (2) to determine whether the time elapsed since preparation
      or number of doses given affected the contamination rate; (3) to determine
      whether any adverse effects resulted from bacterially contaminated drugs.
      METHODS: Prospective, blinded trial exploring the effect of method of
      preparation, time since preparation, and number of doses given on contamination
      rates and infective adverse events associated with bacterially contaminated
      specimens. RESULTS: The rate of bacterial contamination was 12% (95% confidence
      interval 6% to 18%). There was no difference in contamination rate in respect of
      method of preparation, number of doses given, or time since preparation. No
      infective complications were identified. CONCLUSIONS: Abandonment of titrated
      intravenous opioids is not justified by the results. However, there is concern
      about the use of this technique of pain control for immunocompromised patients
      and those with prosthetic heart valves.

PMID- 9023622
TI  - Opportunities for emergency medicine training in Australia.
AB  - Opportunities exist for graduates from the United Kingdom to undertake some of
      their emergency medicine training in Australia. Guidelines for graduates are
      presented on when to travel, how to find a position, what information one should
      obtain about a position, and how to acquire the necessary visa and medical
      registration. A successful visit takes some time to plan and requires cooperation
      between the negotiating parties. The graduate who undertakes training abroad can
      expect to benefit professionally and personally. The development of an
      international exchange network for trainees would streamline the process and
      broaden the appeal to graduates of completing some of their emergency medicine
      training in another country.

PMID- 9023623
TI  - Ocular superglue injury.
AB  - OBJECTIVE: To determine the incidence of ocular injuries associated with
      superglue. METHODS: A retrospective review of patients attending an accident and
      emergency department over a 12 month period with ocular superglue injuries.
      RESULTS: 14 patients who suffered ocular injuries due to superglue were
      identified. No patients had long term complications from their injury. Management
      is discussed. CONCLUSIONS: Superglue eye injuries do not appear to cause long
      term morbidity.

PMID- 9023624
TI  - Neuralgic amyotrophy presenting to an accident and emergency department.
AB  - Two patients with neuralgic amyotrophy (Parsonage-Turner syndrome) are described.
      Problems arising from the shoulder girdle commonly present to accident and
      emergency (A&E) departments. Neuralgic amyotrophy is an infrequent neuromuscular
      disorder which predominantly affects the shoulder girdle. Characterised by severe
      pain followed by muscle weakness, atrophy, and variable sensory deficits, the
      diagnosis is based on history and physical findings and is confirmed by
      electromyography. The prognosis is excellent and treatment is supportive using
      analgesia and physiotherapy.

PMID- 9023625
TI  - Potassium permanganate poisoning--a rare cause of fatal self poisoning.
AB  - Attempted suicide by self poisoning is common because of the ready availability
      of drugs, whether prescribed or bought over the counter. In some cases, the
      ingestion of seemingly innocuous household products or chemicals can result in
      death. Potassium permanganate is an example. Poisoning with potassium
      permanganate can be fatal when a significant amount is ingested, as shown by a
      patient who suffered both the corrosive and systemic toxic effects of this
      chemical.

PMID- 9023626
TI  - Inadvertent intracranial insertion of a nasogastric tube in a non-trauma patient.
AB  - Complications following nasogastric intubation in patients with basal skull
      fractures are well documented. This report is of a rare cause of inadvertent
      intracranial placement of a nasogastric (NG) tube in a non-trauma patient. The
      patient subsequently died. The use of NG tubes, their place in airway management,
      and lessons to be learned from this case are discussed.

PMID- 9023627
TI  - Traumatic asphyxia in children.
AB  - Two cases of traumatic asphyxia in young children are reported. The first was a 2
      year old child run over at low speed by the front wheels of a delivery van. He
      made an uncomplicated recovery. The second child was pinned to the floor by an
      empty chest of drawers in an unwitnessed accident. He was discovered in cardiac
      arrest and resuscitation was unsuccessful. The outcome following traumatic
      asphyxia is a product of duration of compression and the weight involved.
      Considerable weight can be tolerated for a short period, whereas a comparatively
      modest weight applied for a longer period may result in death.

PMID- 9023628
TI  - Neck pain as a presenting symptom in malignant hypertension.
AB  - Neck pain, unrelated to trauma, is relatively common and is usually presumed to
      be musculoskeletal in origin. A patient presented with an unusual and serious
      cause of neck pain-malignant hypertension. The mechanism of the neck pain may be
      incipient tonsillar herniation of the cerebellum caused by raised intracranial
      pressure.

PMID- 9023629
TI  - Necrotising fasciitis as a complication of steroid injection.
AB  - Necrotising fasciitis is described as a complication of steroid injection of a
      painful shoulder in a previously well female. This case highlights a very rare
      life threatening emergency after steroid injection. Early recognition,
      resuscitation, and aggressive surgical management are essential to prevent
      mortality in this condition.

PMID- 9023630
TI  - Oesophageal "cross"--a sinister foreign body.
AB  - A young jail inmate purposely ingested a foreign body formed of sewing needles,
      specially designed to be arrested in the gut and cause perforation. Immediate
      surgical removal of such ingested foreign objects is recommended because the
      chances of distal passage are nil.

PMID- 9023631
TI  - Guidelines for imaging children with head injuries in A&E departments.

PMID- 9023632
TI  - Acute pain management for children in A&E.

PMID- 9023633
TI  - Childhood accidents.

PMID- 9023634
TI  - Topical analgesia for children.

PMID- 9023635
TI  - Fasting before Bier's block.

PMID- 9023637
TI  - GPs in A&E.

PMID- 9023636
TI  - Fasting before Bier's block.

PMID- 9023638
TI  - Paramedic care: the case for minimum intervention.

PMID- 9023639
TI  - HIV-proteinase inhibitors in the management of HIV-infection.

PMID- 9023640
TI  - Effects of omeprazole and amoxycillin on the human oral and gastrointestinal
      microflora in patients with Helicobacter pylori infection.
AB  - Fourteen patients with Helicobacter pylori infection were treated with omeprazole
      capsules 20 mg and amoxycillin capsules 1000 mg twice daily for 14 days and 14
      patients with omeprazole capsules 20 mg and placebo twice daily for 14 days.
      Samples from saliva, dental plaque and faeces and biopsies from antrum and corpus
      were analysed in order to determine the ecological changes in the normal
      microflora. Several microorganisms were affected by both treatment regimens. Two
      patients were colonised with enterobacteria in the oral cavity and stomach during
      the omeprazole plus amoxycillin treatment. A general increase in the number of
      microorganisms from gastric mucosa was observed in both treatment groups. A
      selection of resistant enterobacteria and an increase in beta-lactamase
      production was observed in the faecal samples during the omeprazole plus
      amoxycillin treatment. Eradication of H. pylori in the omeprazole-amoxycillin
      group was 50% and in the omeprazole placebo group 0% four weeks after treatment.
      No viable H. pylori were cultivated in the saliva, dental plaque or faecal
      samples. Treatment with omeprazole 20 mg and amoxycillin 1000 mg twice daily for
      14 days altered the normal microflora in the oral, gastric and intestinal tract
      and antibiotic resistant microorganisms increased in numbers in the intestinal
      microflora.

PMID- 9023641
TI  - Mechanisms responsible for reduced susceptibility to imipenem in Bacteroides
      fragilis.
AB  - The mechanisms responsible for reduced susceptibility to imipenem (MIC 2-16 mg/L)
      were investigated in eight strains of Bacteroides fragilis. All the strains
      produced elevated levels of beta-lactamase. Four B. fragilis strains produced
      metallo-beta-lactamase capable of marked imipenem hydrolysis, and these enzymes
      were shown to be responsible for resistance. There was evidence, from testing
      susceptibility to imipenem in the presence of clavulanic acid, that increased
      resistance in two strains was associated with susceptibility to beta-lactamases
      other than metallo-enzymes. With the remaining two strains there was no evidence
      of enzymic breakdown of imipenem. Neither of these strains showed evidence of
      decreased permeability to nitrocefin as judged by a method which takes into
      account the substrate concentration in the periplasmic space. A low molecular
      weight PBP, that was not seen in fully sensitive strains of B. fragilis, was
      detected in four strains in which reduced susceptibility to imipenem was not
      associated with metallo-beta-lactamase activity.

PMID- 9023642
TI  - Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with
      haematological malignancies.
AB  - The efficacy of oral itraconazole 2 x 200 mg capsules daily for prevention of
      systemic mycoses was investigated in granulocytopenic patients with
      haematological malignancies. Of 241 patients, 197 were evaluable for prophylactic
      efficacy, and 214 for adverse events. Patients with similar characteristics
      receiving oral amphotericin B as antifungal prophylaxis, observed over 15 months
      before introduction of itraconazole, served as control group (n = 223). With
      itraconazole prophylaxis, 13 cases of aspergillosis (9 proven, 1 probable, 3
      possible; 7%) and no systemic yeast infection occurred, compared with 14 episodes
      of aspergillosis (9 proven, 2 probable, 3 possible; 6%) and 3 proven systemic
      yeast infections (Candida albicans, Candida norvegensis, Trichosporon beigelii)
      in the historical group. Adverse events were observed in 13% of evaluable
      patients receiving itraconazole. In four patients with acute lymphoblastic
      leukaemia receiving itraconazole and vincristine simultaneously, severe vinca
      alkaloid-induced neurotoxicity occurred. Plasma concentrations of itraconazole
      and hydroxyitraconazole were measured in 64 patients. After eight days of
      itraconazole the median drug concentration was adequate (700 ng/mL), but there
      was a marked individual variation (229-2861 ng/mL). In comparison with a
      historical group, antifungal prophylaxis with itraconazole reduced the incidence
      of systemic yeast infections, but the frequency of aspergillosis was similar.
      However, a general increasing incidence of aspergillus infections at our hospital
      over the last four years should be considered in the assessment of study results.

PMID- 9023643
TI  - The Etest for antimicrobial susceptibility testing of Bartonella henselae.
AB  - The in-vitro susceptibility of 10 isolates of Bartonella henselae was assessed
      using the Etest. The organisms, one reference human strain and nine feline
      isolates, were grown on chocolate agar and the Etests read at days 5, 8 and 11.
      Six antibiotics, erythromycin, azithromycin, doxycycline, ciprofloxacin,
      rifampicin and vancomycin were evaluated. The results correlated well with
      published results using agar dilution. The results confirmed the high in-vitro
      susceptibility of B. henselae to erythromycin, azithromycin, doxycycline and
      rifampicin and to a lesser extent ciprofloxacin. The majority of isolates were
      resistant to vancomycin. Although in-vitro results of B. henselae susceptibility
      testing may not necessarily correlate with clinical response, the Etest may be a
      simpler way for laboratories to monitor for the development of resistance
      particularly in the setting of relapsing infection.

PMID- 9023644
TI  - A comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural
      fluid in humans: a study of once daily administration by intramuscular and
      intravenous routes.
AB  - Pleural fluid and serum pharmacokinetics of ceftriaxone were performed in
      thirteen patients with pleural effusion. One gram of ceftriaxone was administered
      once daily intravenously in six patients and intramuscularly in seven patients.
      Ceftriaxone concentrations were measured in serum and pleural fluids in both
      groups on the first day of administration and in four patients of the
      intramuscular group on the fourth day of administration. The mean serum peak
      concentration at 1 h was 199 mg/L (S.E.M. 63.2) in the iv group and 80.5 mg/L
      (S.E.M. 12.0) in the im group. The mean serum trough concentrations in the two
      groups at 24 h were 27.5 mg/L (S.E.M. 12.6) and 29.7 mg/L (S.E.M. 5.2)
      respectively. In the pleural fluid, mean peak concentration was 20.1 mg/L (S.E.M.
      4.7) at 6 h in the iv group and 15.3 mg/L (S.E.M. 5.1) at 12 h in the im group.
      The mean trough concentration was 9.6 mg/L (S.E.M. 1.9) and 13.3 mg/L (S.E.M.
      3.1) at 24 h in the two groups respectively. On the fourth day of intramuscular
      administration the serum and pleural fluid peak and trough concentrations were
      higher when compared with the first day, consistent with a cumulative effect. The
      serum and pleural fluid concentrations of ceftriaxone following intravenous and
      intramuscular administration were well above the MIC90 of most common respiratory
      pathogens indicating good penetration into extracellular spaces. Further, these
      serum and pleural fluid antibiotic concentrations could be maintained even after
      a single intramuscular injection of the drug, thus indicating its usefulness as a
      parenteral mode of therapy on a domicilliary basis with a significant cost-saving
      potential. In conclusion, intramuscular administration of ceftriaxone would
      appear to be a convenient method of administering parenteral therapy in lower
      respiratory tract infections in the hospital and community, with pharmacokinetics
      very similar to those exhibited by the intravenous route.

PMID- 9023645
TI  - Pharmacodynamics and pharmacokinetics of A-80556 using microdialysis in a
      Streptococcus pneumoniae meningitis model.
AB  - Using microdialysis in a rabbit model of Streptococcus pneumoniae meningitis, the
      pharmacokinetics and pharmacodynamics of a new fluoroquinolone, A-80556, were
      determined. A-80556 (10 mg/kg iv) was administered to four rabbits. Saline was
      given to four separate control animals. A microdialysis probe perfused the CSF (2
      microL/min) and effluent was collected at 0-0.25, 0.25-1, 1-2, 2-4, and 4-6 h
      after injection of A-80556. Seven blood samples were collected and analyzed by
      HPLC. At 0, 2, 4 and 6 h 300 microL of CSF was withdrawn for pharmacodynamic
      measurements. Plasma A-80556 concentrations demonstrated AUC0-infinity 2.40 +/-
      0.272 micrograms.h/mL; T1/2 beta 1.07 +/- 0.011 h; Vd 6.35 +/- 0.50 L/kg; and Cl1
      4.23 +/- 0.48 L/h.kg. Penetration into the CSF was 18.21%. Pharmacodynamics using
      time-kill curves showed a 3-log reduction in bacterial counts in CSF at 2 h after
      administration continuing for the remaining four hours of the experiment. These
      results demonstrate that microdialysis can be used for determination of drug
      penetration and efficacy in experimental S. pneumoniae meningitis.

PMID- 9023646
TI  - The efficacy of antibiotics enhanced by electrical currents against Pseudomonas
      aeruginosa biofilms.
AB  - Low electrical currents are reported to enhance the activity of tobramycin and
      biocides against biofilm bacteria. We report that the activity of those
      antibiotics to which the bacterium is susceptible in its planktonic state may be
      enhanced by a low electrical current against the more resistant biofilm cells.
      Pseudomonas aeruginosa biofilms were formed on a dialysis membrane suspended
      between two parallel electrode plates in an electrical colonisation cell.
      Ciprofloxacin, polymyxin B and piperacillin were tested on biofilms at ten times
      their MIC for 12 h in the presence of 0 (control) and 9 mA/cm2 current density.
      At these concentrations the antibiotics alone reduced the biofilm population, but
      in the presence of an electrical current the population was further reduced by
      ciprofloxacin and polymyxin B though not by piperacillin. Exposure of the
      planktonic bacteria to the same concentrations of antibiotics demonstrated that
      ciprofloxacin and polymyxin B reduced the population to below 1% after 12 h and
      below 0.1% after 24 h, while piperacillin was bacteriostatic. The results suggest
      that the electrical current can enhance the activity against biofilms of only
      those antibiotics that are effective against planktonic cells.

PMID- 9023647
TI  - Optimising antimicrobial drug use in surgery: an intervention study in a Dutch
      university hospital.
AB  - Following a one-month prospective study of antimicrobial drug use in surgical
      departments, new guidelines were implemented. The review was repeated after two
      years. In both study periods, one third of patients were prescribed antimicrobial
      drugs. Prophylactic antibiotic consumption decreased from 0.75 to 0.53 defined
      daily doses/operation. Compliance with guidelines improved from 32% to 79%.
      Duration of prophylaxis > 24 h decreased from 21% to 8%. Single dose prophylaxis
      increased from 34% to 80%. Quality of the prophylactic courses improved, as
      evaluated by experts using established criteria. For prophylaxis, cost savings
      amounted to 57%. Better quality of therapeutic courses was associated with a cost
      increase of 15%. Indicators of satisfactory outcome with the new policy were a
      stable median length of stay (5.5 days in the first review and 5.0 days after
      intervention) and a reduction in the number of nosocomial infections treated with
      antimicrobial drugs/100 bed days (1.0 before intervention vs 0.77 after
      intervention).

PMID- 9023648
TI  - Potential effects of amoxycillin/clavulanic acid and ticarcillin/clavulanic acid
      on human granulocyte activity: a comparative study.
AB  - The efficacy of an antimicrobial agent in the therapy of infection depends upon
      the interaction of bacteria, antibiotic and phagocytes. The influence of both
      ticarcillin/clavulanic acid and amoxycillin/clavulanic acid on the phagocytic and
      bactericidal activity of human PMNs in vitro was investigated. The results show
      that clavulanic acid, with its beta-lactamase inhibitory properties, potentiated
      the efficacy of both ticarcillin and amoxycillin, resulting in a significantly
      increased susceptibility of a beta-lactamase producing strain of Klebsiella
      pneumoniae to phagocytic and microbicidal activities of human PMNs. Overall,
      amoxycillin/clavulanic acid showed greater enhancement of the killing of K.
      pneumoniae by human PMNs.

PMID- 9023649
TI  - The tolerance and pharmacokinetics of clinafloxacin (CI-960) in healthy subjects.
AB  - The single-dose tolerance and pharmacokinetics of clinafloxacin, a new
      fluoroquinolone antibacterial agent, were evaluated in healthy volunteers. Single
      oral doses of 25, 50, 100, and 200 mg were well tolerated. Adverse events after
      placebo and clinafloxacin were similar, with mild drowsiness, dizziness,
      headache, and rash being reported most frequently. The frequency and intensity of
      side-effects did not increase with dose. Clinafloxacin was rapidly absorbed, with
      Cmax occurring at approximately 40 min postdose. Plasma concentrations increased
      proportionately and, following 100 or 200 mg doses, remained above MIC90s
      required for most nosocomial pathogens for at least 12 h. Clinafloxacin
      elimination half-life averaged 5.2 h and renal clearance was approximately 200
      mL/min. About 50% of the administered dose was excreted unchanged in the urine.

PMID- 9023650
TI  - Resistance to bismuth among gram-negative bacteria is dependent upon iron and its
      uptake.
AB  - Bismuth antimicrobial action is poorly understood. Many trivalent metals possess
      antibacterial activity, especially under low iron conditions. Protection of
      bacteria from the deleterious effects of bismuth and other trivalent metals was
      demonstrated in iron-fortified media. Near-equimolar quantities of Fe3+
      neutralized the growth-inhibitory effects of 250 microM Bi3+. Resistance to
      bismuth action also depended on the production of virulence-related siderophores.
      Escherichia coli, Aeromonas hydrophila or Pseudomonas aeruginosa producing
      aerobactin, amonabactin or pyoverdin respectively, were most resistant to Bi3+.
      Enterochelin or pyochelin producers were less resistant to Bi3+, but more
      resistant than strains lacking siderophores. Purified pyoverdin restored Bi3+
      resistance in a mutant lacking this siderophore, but not in one lacking the
      pyoverdin receptor. Bismuth-treated bacteria exhibited unique outer membrane
      proteins, similar in size to iron-repressible proteins. Thus, resistance to the
      inhibitory action of Bi3+ among Gram-negative bacteria is inversely related to
      iron concentration and strongly dependent on iron transport mechanisms. The data
      suggest that bismuth action is largely a nonspecific, competitive interference
      with iron-transport, related primarily to atomic valence Furthermore, resistance
      to Bi3+ among bacteria is predictive of virulence.

PMID- 9023652
TI  - Inhibition of the respiration of multi-drug resistant clinical isolates of
      Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of
      freshly diagnosed tuberculosis.
AB  - Chlorpromazine and thioridazine are phenothiazines employed in the treatment of
      psychosis. These agents inhibited the respiration of clinical isolates of
      Mycobacterium tuberculosis resistant to streptomycin, rifampin, isoniazid,
      ethambutol and/or pyrazinamid, all first line drugs. Since any adverse reaction
      to thioridazine is generally less severe than to chlorpromazine, the possibility
      is attractive that thioridazine may have a potential in the initial management of
      patients with newly diagnosed tuberculosis with an as yet undetermined antibiotic
      susceptibility profile.

PMID- 9023651
TI  - The activities of four anticancer alkyllysophospholipids against Leishmania
      donovani, Trypanosoma cruzi and Trypanosoma brucei.
AB  - The in-vitro activities of four anticancer alkyllysophospholipids, ET-18-OCH3
      (edelfosine), hexadecylphosphocholine (miltefosine), ilmofosine and SRI 62-834,
      were determined with ED50 values for Leishmania donovani and Trypanosoma cruzi
      amastigotes between 0.2 and 5.0 microM and for Trypanosoma brucei trypomastigotes
      between 7.0 and 50.8 microM. In BALB/c mice miltefosine and ilmofosine were the
      most active compounds with ED50 values of 2.9 and 14.5 mg/kg x 5 doses against L.
      donovani and a suppressive effect on T. cruzi infections at 30 mg/kg x 5 doses.

PMID- 9023653
TI  - Bactericidal activity, post antibiotic effect and modified controlled effective
      regrowth time of meropenem at high concentrations.
AB  - The effect of increasing meropenem concentrations up to 250 mg/L, as might occur
      if 3 g was given as a single daily intravenous dose, was investigated in terms of
      bactericidal activity, post antibiotic effect (PAE) and modified controlled
      effective regrowth time (mCERT). Increasing the meropenem concentration above 50
      mg/L did not result in increased bacterial killing, while concentrations over 75
      mg/L did not result in longer PAE or mCERT.

PMID- 9023654
TI  - Bactericidal activity of trovafloxacin (CP-99,219).
AB  - Trovafloxacin was found to be a typical quinolone producing a biphasic dose
      response against Escherichia coli, Staphylococcus aureus or Streptococcus
      pneumoniae. A reduced rate of kill was seen against Enterococcus faecalis, which
      is also typical of the quinolones. However, the bactericidal activity of
      trovafloxacin against S. aureus and S. pneumoniae was greater than most other
      quinolones previously tested. The enhanced bactericidal activity of trovafloxacin
      against S. aureus may be explained by the possession of a very strong
      bactericidal mechanism B. Trovafloxacin may prove to be a quinolone of choice
      against S. aureus infections.

PMID- 9023655
TI  - In-vitro bactericidal activity of cefpirome in combination with vancomycin
      against Staphylococcus aureus and coagulase-negative staphylococci.
AB  - In an in-vitro study of the bactericidal activity of cefpirome in combination
      with vancomycin against 11 clinical isolates of staphylococci, cefpirome at a
      concentration of 0.25 times the MIC acted synergistically with vancomycin (at a
      concentration of 0.5, 1 or 2 times the MIC) against Staphylococcus aureus and
      coagulase-negative staphylococci susceptible or resistant to methicillin.
      Moreover, increasing the cefpirome concentration to 0.5 or 1 times the MIC
      combined with vancomycin at the same concentration (0.5 or 1 times the MIC)
      improved the bacterial killing rate; a bactericidal effect was obtained in 9 or
      24 h instead of in 24 or 48 h, respectively.

PMID- 9023656
TI  - The in-vitro activity of an antifungal antibiotic benanomicin A in comparison
      with amphotericin B.
AB  - Benanomicin A showed a broad antifungal spectrum, inhibiting the growth of all
      test strains of 41 yeasts, 23 dimorphic fungi, 23 dematiaceous fungi, 16
      aspergilli, and 19 dermatophytes, with the exception of 12 zygomycetic strains.
      The MIC values of benanomicin A were comparable to those of amphotericin B
      against Cryptococcus. Rhodotorula, Trichosporon, Geotrichum, Sporothrix, and some
      dermatophytes, but were two to eightfold higher than those of amphotericin B
      against other fungal pathogens tested. The action of benanomicin A was
      fungicidal.

PMID- 9023657
TI  - Characterisation of DNA gyrase and measurement of drug accumulation in clinical
      isolates of Acinetobacter baumannii resistant to fluoroquinolones.
AB  - Twelve clinical isolates of Acinetobacter baumannii highly resistant to
      pefloxacin (MIC > or = 32 mg/L) and to ciprofloxacin (MIC > or = 16 mg/L), were
      studied. A susceptible isolate used as a reference (MIC of 0.032 and 0.25 mg/L
      for ciprofloxacin and pefloxacin, respectively) accumulated 85 mg of pefloxacin
      per litre of cell volume within 10 min, from a solution containing 10 mg/L of
      antibiotic. One resistant isolate accumulated the same amount of pefloxacin,
      while the 11 others accumulated between 40 and 70 mg/L of cell volume. The
      differences between reference and resistant isolates with respect to
      ciprofloxacin and sparfloxacin accumulation were less pronounced. There were no
      apparent differences in the outer membrane protein profiles of susceptible and
      resistant isolates. DNA gyrase was isolated from four A. baumannii and the
      minimum concentration of fluoroquinolones, required to inhibit gyrase-catalysed
      supercoiling of plasmid DNA was 5- to 80-fold higher for the resistant isolates
      than for the reference strain. Although most isolates showed some degree of
      reduced fluoroquinolone accumulation, a DNA gyrase mutation was more likely to be
      the main mechanism of the high level resistance encountered.

PMID- 9023658
TI  - Killing kinetics of meropenem against penicillin-resistant pneumococci.
AB  - The killing kinetics of meropenem against sixteen clinical isolates of
      pneumococci (12 penicillin-resistant, three penicillin-intermediate and one
      penicillin-sensitive) were studied. Meropenem was tested at 1x, 2x and 4x the MIC
      for each individual isolate. The results showed a good bactericidal activity with
      rapid killing of pneumococci (killing > 3 log10 cfu/mL was obtained for nine
      strains). This strategy needs clinical assessment and might prove to be a
      suitable alternative to penicillin and cephalosporins for the treatment of mixed
      infections involving multiresistant pneumococci.

PMID- 9023659
TI  - Bolus or infusion teicoplanin for intravascular catheter associated infections in
      immunocompromised patients?
AB  - An unexpected low efficacy of teicoplanin in the treatment of coagulase negative
      staphylococcal (CNS) infections on a regional Bone Marrow Transplant (BMT) Unit
      led to a retrospective study. CNS infections treated with gylcopeptides in BMT
      patients with in-dwelling central venous lines between May 1990 and May 1995 were
      reviewed. Efficacy rates of 50% for teicoplanin compared with 80% for vancomycin
      despite comparable antibiotic susceptibility. Glycopeptides have bactericidal
      action which is time dependent. Teicoplanin was administered by bolus injection
      during the study period and it is suggested that this observed difference in
      efficacy is caused by the short duration of exposure of luminal bacteria.

PMID- 9023660
TI  - Trends in-original research published from the United Kingdom in the
      antimicrobial chemotherapy literature, 1980-1994.
AB  - There is a feeling that the contribution of researchers from the United Kingdom
      in the antimicrobial chemotherapy area is in decline, and we, therefore, reviewed
      publications in the Journal of Antimicrobial Chemotherapy (JAC) and Antimicrobial
      Agents and Chemotherapy (AAC) in 4 of the last 14 years. In absolute numbers the
      total number of UK first author publications in these two journals were 103, 78,
      107 and 82 in 1980, 1985, 1990 and 1994 respectively. The percentage of first
      author papers from the UK in JAC was 35%, 21%, 24%, 23% and in AAC was 5.7%,
      4.9%, 5.1% and 4.7% for the years 1980, 1985, 1990 and 1994 respectively. Within
      the UK there has been a relative decline in the number of publications produced
      by NHS hospital departments and an increase in those produced by universities.
      Ten institutions (four universities, two pharmaceutical companies and four NHS
      departments) produced almost half of the UK publications. There is no room for
      complacency about the state of British antimicrobial research and the relative
      decline in the NHS hospital sector's contribution, the largest contributor
      numerically, even before the full impact of the ongoing NHS reforms, is cause for
      concern.

PMID- 9023662
TI  - In-vitro and in-vivo activities of antibiotics on Yersinia enterocolitica.

PMID- 9023661
TI  - In-vitro activity of antimicrobial agent combinations against multiresistant
      Acinetobacter baumannii.

PMID- 9023663
TI  - Non-enzyme mediated beta-lactam resistance in Haemophilus influenzae.

PMID- 9023664
TI  - Identification of mec-related oxacillin resistance in staphylococci by the Etest.

PMID- 9023665
TI  - The comparative efficacy and safety of teicoplanin and vancomycin.

PMID- 9023666
TI  - Insertion of a carbapenemase gene cassette into an integron of a Pseudomonas
      aeruginosa plasmid.

PMID- 9023667
TI  - Review: Ca2+ channel sub-types in peripheral efferent autonomic nerves.

PMID- 9023668
TI  - Effect of clenbuterol on the modulation of noradrenaline release in the rat tail
      artery.
AB  - 1. Exposure of rat tail arteries to clenbuterol, a beta 2-adrenoceptor agonist,
      for 20 or 90 min, did not change or increase, respectively, tritium overflow
      induced by electrical field stimulation in arteries preincubated with [3H]
      noradrenaline (NA). This facilitatory effect was antagonized by propranolol. 2.
      Phentolamine increased the evoked overflow four-fold, which was not modified by
      90 min incubation with clenbuterol. In rats pretreated with clenbuterol for 2
      weeks, the stimulated overflow was not enhanced by this beta 2-agonist, and the
      increase produced by phentolamine was markedly diminished. 3. Contractile
      responses induced by electrical field stimulation were not modified or increased
      (only at low frequencies) by preincubation with clenbuterol for 20 or 90 min,
      respectively. This effect was inhibited by propranolol. 4. In arteries
      precontracted with 5-hydroxytryptamine, clenbuterol (10 nM-10 microM) produced
      small relaxations, which were reduced by propranolol plus phentolamine and not
      modified by phentolamine or 90 min exposure to clenbuterol. 5. These results
      indicate that prolonged exposure of rat tail arteries to clenbuterol produces a
      facilitation of NA release mediated by activation of presynaptic beta 2
      adrenoceptors, which may be involved on the enhancement of contractile responses
      to electrical stimulation induced by clenbuterol. However, chronic treatment with
      this beta-agonist desensitizes these receptors.

PMID- 9023669
TI  - Effect of several bicyclic peptide and cyclic pseudopeptide tachykinin NK2
      receptor antagonists in the human isolated urinary bladder.
AB  - 1. We have studied several tachykinin NK2 receptor antagonists, bearing a
      monocyclic pseudopeptide (MEN 10,508, MEN 10,573, MEN 10,581, MEN 10,612, MEN
      10,619 and MEN 10,677), or bicyclic peptide (MEN 10,627, MEN 10,692, MEN 10,771,
      MEN 10,882 and MEN 10,993) structure, on the human isolated urinary bladder
      detrusor muscle against neurokinin A as an agonist, and compared their affinities
      in this preparation with those for NK2 receptors expressed in the rabbit isolated
      pulmonary artery and hamster isolated trachea. 2. In the human bladder, all the
      antagonists tested produced a concentration-dependent and competitive antagonism
      of neurokinin A-mediated contractions: among the cyclic pseudopeptides MEN 10,677
      (pKB = 8.0) was the most potent antagonist, while among the bicyclic analogues it
      was MEN 10,993 (pKB = 8.8). 3. In general, the bicyclic peptide antagonists
      tested were more potent than the monocyclic pseudopeptide compounds, either in
      the human urinary bladder or in the rabbit pulmonary artery or hamster trachea,
      showing a nanomolar affinity for the human NK2 receptor. 4. A highly significant
      correlation was found between the estimated pKB values of all the antagonists
      tested in the human urinary bladder and rabbit pulmonary artery (r2 = 0.94, n =
      12, P < 0.01), whereas no linear correlation was found between pKB values
      measured in the human urinary bladder and hamster trachea (r2 = 0.52, n = 12, P >
      0.05): these observations provide further pharmacological evidence for receptor
      homology between the human and rabbit NK2 receptor. 5. The present results point
      out the class of NK2 receptor antagonists bearing a bicyclic peptide structure,
      like MEN 10,627, as candidates for testing in pathological conditions, such as
      bladder hyperactivity, for which preclinical evidence indicates that a
      therapeutic effect could result from the block of the tachykinin NK2 receptor.

PMID- 9023670
TI  - Oxidized low-density lipoproteins inhibit endothelium-dependent relaxations in
      isolated large and small rabbit coronary arteries.
AB  - 1. Previous studies suggest that oxidatively modified low-density lipoproteins
      (oxLDL) contribute to the impairment of endothelium-dependent vasodilation in the
      large arteries of hypercholesterolaemic animals, whereas this may not be the case
      with regard to the impairment of coronary resistance vessels. For this reason,
      the effect of lipoproteins on coronary resistance arteries has been examined in
      this study. 2. The influence of lipoproteins on endothelium-dependent relaxation
      induced by acetylcholine (ACh) or sodium nitroprusside in PGF2 alpha
      preconstricted rings from the large (1st order branch) and small coronary
      arteries (3rd order branch) and the aorta of New Zealand White rabbits, was
      investigated. 3. The sensitivity to ACh was greater in the large compared with
      the small diameter coronary arteries. 4. Endothelium-dependent relaxations were
      unaffected by native LDL. Oxidized LDL (0.5 and 1 mg protein mL-1) caused a
      reversible inhibition of relaxations in both preconstricted small and large
      coronary arteries which was overcome at high ACh concentrations. Similar
      inhibitions were found in the aorta. 5. Endothelium-independent relaxations
      elicited by sodium nitroprusside in the large and small coronary arteries were
      unaffected by the oxidized lipoproteins, indicating that soluble guanylate
      cyclase activity was unaltered. 6. It is concluded that inhibition of endothelium
      dependent relaxation in the small diameter coronary arteries in
      hypercholesterolaemia may arise from products of oxidative modification of LDL
      present in the artery itself or released upstream from proximal lesions.

PMID- 9023671
TI  - Changes in cardiovascular responsiveness to dopexamine and beta 1- and beta 2
      adrenoceptor function after the chronic treatment of beta-adrenoceptor
      antagonists and agonists in anaesthetized dogs.
AB  - 1. The studies were designed to investigate the changes in responsiveness to beta
      adrenoceptor agonists induced by chronic administration of beta-adrenoceptor
      antagonists and agonists. 2. Dose-response curves for dopexamine, isoprenaline,
      noradrenaline and impromidine on heart rate, blood pressure and myocardial
      contractility (dP/dt:integrated isometric tension) were obtained in untreated
      dogs and compared to those measured in dogs which had been pretreated with
      propranolol (8 mg kg-1 day-1), atenolol (6 mg kg-1 day-1), isoprenaline (0.5
      microgram kg-1 min-1) or noradrenaline (0.5 microgram kg-1 min-1) for 14 days. 3.
      Propranolol pretreatment significantly enhanced the inotropic and chronotropic
      responses to isoprenaline. There were noticeable, but non-significant increases
      in inotropic sensitivity to noradrenaline and dopexamine, especially at higher
      dose levels. In the atenolol treatment group, there were significant increases in
      inotropic responses to dopexamine and isoprenaline and in depressor responses to
      isoprenaline. 4. Thus, chronic administration of propranolol increased responses
      mediated by both beta 1- and beta 2-adrenoceptors, whereas, atenolol selectively
      enhanced the inotropic responsiveness to dopexamine, which is mediated mainly by
      beta 2-adrenoceptors. 5. Isoprenaline pretreatment caused a significant decrease
      in inotropic sensitivity to dopexamine, isoprenaline and noradrenaline and a
      significant reduction in chronotropic responses to dopexamine. The tendency to
      reduced depressor responses to isoprenaline and dopexamine failed to reach
      significance. Pretreatment with noradrenaline decreased only the inotropic
      response to noradrenaline. 6. Thus, chronic isoprenaline treatment reduced the
      responsiveness of both beta 1- and beta 2-adrenoceptors, while chronic
      noradrenaline infusion only reduced beta 1-adrenoceptor-mediated responses. 7.
      There was no significant change in any of the dose-response curves to impromidine
      after any beta-adrenoceptor antagonist or agonist treatment. This indicates that
      there was no non-specific alteration in responsiveness and that the observed
      changes were likely to be associated with specific alterations in beta
      adrenoceptor number or function.

PMID- 9023672
TI  - McN-A-343 increases renal sympathetic nerve activity and blood pressure by a
      muscarinic and a non-muscarinic mechanism in the rat.
AB  - 1. Intravenous administration of the putative M1 muscarinic agonist McN-A-343 to
      conscious rats evokes an increase in mean arterial pressure (MAP) which can be
      blocked by muscarinic receptor antagonists. The present study was undertaken to
      evaluate the increase in MAP and renal sympathetic nerve activity (RSNA) evoked
      by intravenous administration of McN-A-343 to urethane-anaesthetized rats. 2. McN
      A-343 (0.1-0.3 mg kg-1) evoked a concurrent increase in MAP and RSNA which could
      be inhibited by the nonselective muscarinic receptor antagonist methylatropine or
      the selective M1 muscarinic receptor antagonist telenzepine. Administration of
      higher doses of McN-A-343 (0.3-1.2 mg kg-1) in the presence of muscarinic
      receptor blockade evoked brief bursts in RSNA accompanied by increases in MAP. 3.
      The increases in MAP, but not the increases in RSNA, evoked by all doses of McN-A
      343 could be attenuated by the selective alpha 1-adrenoceptor antagonist
      prazosin. Adding the selective alpha 2-adrenoceptor antagonist yohimbine to
      prazosin did not further inhibit the pressor response to the low doses of McN-A
      343. 4. The irreversible alpha-adrenoceptor and NPY receptor antagonist
      benextramine also attenuated the pressor response evoked by the low doses of McN
      A-343 but not the increases in RSNA. However, when combined with muscarinic
      receptor blockade, benextramine completely inhibited the brief bursts in RSNA,
      and thus also the increases in MAP, evoked by the high doses of McN-A-343. 5. The
      pressor response remaining after the administration of high doses of McN-A-343 to
      rats pretreated with prazosin and methylatropine was inhibited by treatment with
      alpha,beta-methylene ATP. 6. These results show that McN-A-343 evokes increases
      in RSNA by muscarinic and non-muscarinic mechanisms. Furthermore, the subsequent
      increase in MAP is primarily dependent upon activation of vascular alpha 1
      adrenoceptors, but may also involve activation of P2 alpha receptors.

PMID- 9023673
TI  - [Lesion-related factors associated with restenosis after percutaneous
      transluminal coronary angioplasty in the absence of patient-related factors].
AB  - Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is one of
      the biggest problems in the treatment of coronary artery disease. Although many
      studies have been performed on lesion-related factors, they are influenced by
      patient-related factors such as smoking, hyperlipidemia, and the presence of
      acute coronary syndrome. In this study, lesion-related factors were assessed in
      the absence of other factors by univariate and multivariate analysis. One hundred
      and nine lesions were reviewed in 37 consecutive patients with both restenotic
      lesion(s) and non-restenotic one(s) confirmed by coronary arteriography performed
      4.4 +/- 2.2 months after PTCA. Angiographic findings before and immediately after
      angioplasty were compared between restenotic and non-restenotic lesions. The
      overall lesion-restenosis rate was 42%. Univariate analysis revealed that
      calcified lesions (p < 0.05), multiple irregularities (p < 0.01) before
      angioplasty, residual percentage stenosis (p < 0.05), and angiographical
      intraluminal haziness (p < 0.05) were related to restenosis. Intimal dissection
      after PTCA was not associated with restenosis. Multivariate analysis with
      multiple logistic regression revealed that multiple irregularities (t = 2.8) was
      the most predictive of restenosis before PTCA and residual percent stenosis (t =
      2.6) after the procedure. Coronary lesions with calcification or multiple
      irregularities indicate high risk of restenosis after PTCA. Optimal dilatation of
      the lesions without intraluminal haziness regardless of intimal dissection is
      important to prevent restenosis.

PMID- 9023674
TI  - [Identification of predictive factors associated with recurrent restenosis after
      second percutaneous transluminal coronary angioplasty].
AB  - The predictive factors of a second restenosis after repeated percutaneous
      transluminal coronary angioplasty (PTCA) were investigated by review of the
      records of 100 consecutive patients who underwent second angioplasty for
      restenosis of the same site. PTCA was successful in 97 (97%) of these patients,
      but 38 patients (39%) developed a second restenosis (recurrent restenosis group)
      and 59 did not (no recurrent restenosis group). The clinical, angiographic and
      procedural factors at the second PTCA of the two groups of patients were
      compared. The major risk factors (hypertension, diabetes mellitus,
      hyperlipidemia) and type and morphology of the lesion (eccentricity,
      calcification, length, bend) at repeat PTCA did not differ significantly between
      the recurrent restenosis and no recurrent restenosis groups. The mean intervals
      from the initial to the second PTCA were significantly shorter in the recurrent
      stenosis group than in the no recurrent restenosis group (2.1 +/- 1.1 vs 3.4 +/-
      1.3 months, p < 0.001). Sixteen (76%) of 21 patients had a second restenosis at
      an interval between the two PTCAs of < 3 months, compared with 22 (29%) of 76
      patients with an interval of > or = 3 months (p < 0.001). Patients who undergo a
      second angioplasty procedure within 3 months from the previous procedure at the
      same site have a much higher risk of recurrent restenosis and these patients may
      benefit from an alternative therapeutic approach.

PMID- 9023675
TI  - [Indication for percutaneous transluminal coronary angioplasty based on quality
      of life of patients with angina pectoris].
AB  - The changes in quality of life (QOL) before and after percutaneous transluminal
      coronary angioplasty (PTCA) were investigated to establish criteria for
      determining whether patients with angina pectoris should undergo PTCA. The QOL
      was surveyed twice by self-completed questionnaire for QOL by Iida and Kohashi
      (QUIK) before and about 4 months after PTCA in 84 patients (mean age 62.8 +/-
      10.1 years) with angina pectoris. High QUIK score reflects a poor QOL, of which
      the internal consistency was 0.86, demonstrating high reliability. The subjects
      were classified into three groups according to the changes of total QUIK score
      before and after PTCA (I: QOL improved 31.0%, II: QOL unchanged 48.8%, III: QOL
      worsened 20.2%). Age, gender, total QUIK score prior to PTCA, presence of anginal
      pain, complications extent and degree of coronary artery stenosis, and left
      ventricular ejection fraction were compared between the three groups. The total
      QUIK score prior to PTCA in the improved QOL group was higher than that in the
      worsened QOL group (11.6 vs 5.1, p < 0.01). Most patients showing a poor QOL
      prior to PTCA demonstrated an improvement in their QOL after PTCA. The number of
      patients with anginal pain prior to PTCA was high in the improved QOL group
      (35.8%, p < 0.05). Percutaneous transluminal coronary angioplasty might not
      aggravate QOL (12.1%, p = 0.1) in patients with single-vessel disease. In
      patients with multivessel disease, PTCA might not improve (35.3%) but also might
      aggravate QOL (25.5%). Multivariate analysis showed that PTCA improved QOL in
      male or sixty-ager patients and in patients with a total QUIK score of 10 or more
      prior to PTCA (p < 0.01). The total QUIK score, presence of anginal pain and
      extent of coronary artery stenosis prior to PTCA, gender and age are factors
      predicting QOL after PTCA. The adaptation of PTCA for those patients should be
      prudently and inclusively taken into consideration to extend their QOL.

PMID- 9023676
TI  - [Semi-supervised exercise using a step machine at home after myocardial
      infarction].
AB  - Home exercise programs for patients with myocardial infarction effectively
      improve their ability to exercise as well as quality of life. However, there are
      no efficient methods for monitoring the patient's clinical status or conveying
      the physician's instructions to the home setting. To resolve these problems, we
      developed a computer-based, automated, telemetry system comprised of central and
      peripheral computers and telephone line. Five myocardial infarction patients were
      evaluated for peak oxygen uptake (peak VO2) and anaerobic threshold (AT) before
      hospital discharge. At home, the patients performed 10-min exercise using a step
      machine. Patient data including blood pressure, pulse rate, and electrocardiogram
      before and after exercise were stored in the peripheral computer, and the central
      computer automatically retrieved the data through the phone line. If the current
      heart rate was less than the heart rate at AT, extreme changes in blood pressure
      were noted or dangerous arrhythmias appeared, appropriate instructions were
      indicated on the display of the peripheral computer. Following these
      instructions, the patients continued home exercise programs for 6 months. Peak
      VO2 and AT increased significantly in all patients (peak VO2: baseline 24 +/- 3.3
      ml/kg/min, 6 months later 33.3 +/- 3.7 ml/kg/min, p < 0.01, AT: baseline 15.2 +/-
      2.7 ml/kg/min, 6 months later 18.5 +/- 2.8 ml/kg/min, p < 0.01). The computer
      based automated telemetry system combined with a step machine facilitated
      effective prescription and monitoring of exercise programs at home.

PMID- 9023677
TI  - [Changes in the extent of mitral regurgitation during hemodialysis: color Doppler
      echocardiographic study].
AB  - The changes in the extent of mitral regurgitation (MR) during maintenance
      hemodialysis patients were studied in six patients with MR by color Doppler
      echocardiography. M-mode, two-dimensional and color Doppler echocardiography were
      performed before and every hour during hemodialysis. The severity of MR was
      evaluated by a semiquantitative grading system and maximal MR area. Hemodialysis
      removed 2.1 +/- 0.9/body fluid. Blood pressure and heart rate did not change
      systematically by hemodialysis. Left atrial, left ventricular end-diastolic and
      end-systolic dimensions were significantly decreased by hemodialysis (p < 0.05).
      Stroke volume and left ventricular wall stress were also significantly decreased
      (p < 0.01). MR area was significantly smaller at the end of hemodialysis compared
      to pre-hemodialysis (49.0 +/- 20.5 vs 171.0 +/- 49.2 mm2, p < 0.05). During
      hemodialysis, the extent of MR was continuously decreased. In two out of six
      patients, the MR jet disappeared. The extent of MR may depend on the fluid volume
      removed by hemodialysis because the MR area diminished more as more fluid was
      removed. No major disorders of the mitral complex were detected when the MR area
      was decreased rapidly to less than 60 mm2 in response to the removal of a small
      amount of fluid. The dry weight should be determined as the body weight when MR
      is as small as possible by color Doppler echocardiography.

PMID- 9023678
TI  - Serial histopathologic myocardial findings in a patient with ectopic atrial
      tachycardia-induced cardiomyopathy.
AB  - A 17-year-old woman was found to have ectopic atrial tachycardia by her
      physician. Echocardiography and cardiac catheterization revealed findings
      resembling dilated cardiomyopathy at the time of initial presentation. The
      tachycardia was controlled with atenolol only at a dose of 50 mg/day. However, at
      the age of 22, the presence of ectopic atrial tachycardia was once again
      confirmed. We successfully performed catheter ablation for persistent ectopic
      atrial tachycardia. Serial echocardiographic findings showed the left ventricular
      dimension and function appeared to return to normal 1 year postablation. However,
      despite pharmacologic control and catheter ablation therapy, histopathology
      revealed myocardial fibrosis presumably representing permanent damage of the
      heart secondary to tachycardia 1 year postablation.

PMID- 9023679
TI  - Abnormal echo adjacent to the pulmonary artery in a 70-year-old man.

PMID- 9023691
TI  - Value of axillary ultrasonography and sonographically guided puncture of axillary
      nodes: a prospective study in 144 consecutive patients.
AB  - The value of axillary sonography in 144 consecutive patients was prospectively
      studied. Abnormal lymph nodes were demonstrated in 72 axillae, only half (36 of
      72) of which were clinically detected. In comparison with intraoperative findings
      in 47 patients with breast carcinoma, the sensitivity of sonography in detecting
      malignant nodes was 92%, the specificity 95%, and the positive and negative
      predictive value 96% and 91%, respectively. In 42 patients a sonographically
      guided node puncture was performed. Evidence of malignancy was found in 38
      (90.5%). In 14 (33%) of them, cyto-histology pointed to a clinically undetected
      primary malignancy.

PMID- 9023692
TI  - Sonographic and Doppler flow characteristics of ovarian tumors of low-malignant
      potential.
AB  - OBJECTIVE: To outline the sonographic and color Doppler flow imaging
      characteristics of ovarian tumors of low-malignant potential (OCLMP). METHODS:
      Fourteen women with ovarian tumors of low-malignant potential were compared with
      26 women with ovarian cystadenomas and 23 with ovarian carcinomas. RESULTS:
      Sonographically, more complex structures and echogenic lesions were found in the
      OCLMP and malignant tumors than in the cystadenomas, and the difference was
      statistically significant. Color blood flow imaging revealed a similar resistant
      index (RI) in the OCLMP (0.487 +/- 0.07) and cystadenomas (0.489 +/- 0.09) when
      compared with statistically significant lower RI in the ovarian carcinomas (0.391
      +/- 0.05) (P < 0.001). CONCLUSIONS: Among young women, the combination of a
      complex ovarian mass with turbid fluid and echogenic lesions whose color Doppler
      flow imaging registers in the low range (RI < 0.5) should raise the suspicion of
      an ovarian tumor of low-malignant potential.

PMID- 9023693
TI  - Thyroid autonomy with color-coded image-directed Doppler sonography: internal
      hypervascularization for the recognition of autonomous adenomas.
AB  - In a prospective study, we assessed the possibility of recognizing autonomous
      adenomas of the thyroid with color-coded image-directed Doppler sonography using
      internal hypervascularization in thyroid nodules for identification. Fifty-three
      patients with thyroid nodules underwent additional CCDS examination and nuclear
      scintigraphy (reference). Of 29 patients having autonomous adenomas, 28 patients
      presented internal hypervascularization in their nodules resulting in a
      sensitivity of 96% and a specificity was 75%. Interestingly CCDS detected six
      adenomas in patients showing normal laboratory data (bTSH, TT3, FT4). CCDS could
      be used to exclude focal adenomas with a negative predictive value of 94%. The
      positive predictive value for adenoma was 82%.

PMID- 9023694
TI  - Evaluation of vascular patterns of cervical lymph nodes with power Doppler
      sonography.
AB  - Power Doppler sonography was used to evaluate 105 benign and malignant cervical
      lymph nodes in 60 patients. Three main vascular patterns were identified: type I
      (single vascular pole), type II (hypertrophic vascular pole), and type III
      (mainly peripheral vascularity). The first one was related to chronic
      inflammation (sensitivity 85%, specificity 90%); the second and third were
      related, to a lesser extent, to acute inflammation and neoplasm (sensitivity 68%
      and 55%, specificity 47% and 91%, respectively). The authors conclude that the
      sensitivity and specificity of power Doppler sonography cannot compete with those
      of fine-needle aspiration biopsy in the diagnosis of adenopathy.

PMID- 9023695
TI  - "String sign" of portal vein as precursor of portal thrombosis: color Doppler
      ultrasonographic study of one case.

PMID- 9023696
TI  - Primary hyperparathyroidism: functioning hemorrhagic parathyroid cyst.

PMID- 9023697
TI  - Amputation stump neuroma: ultrasound features.

PMID- 9023698
TI  - Tuberous sclerosis presenting as bilateral flank masses in an infant.

PMID- 9023699
TI  - Three-dimensional ultrasound and hysteroscopy in the evaluation of intrauterine
      retained fetal bones.

PMID- 9023700
TI  - JSID Tanioku Memorial Lecture 1996. Genetic disorders of keratins and their
      associated proteins.
AB  - It has recently been demonstrated that genetic defects in keratin genes cause a
      number of different skin disorders, including epidermolysis bullosa simplex
      (EBS), epidermolytic hyperkeratosis (EH), the EH form of epidermal nevi,
      epidermolytic and non-epidermolytic forms of palmoplantar keratoderma (EPPK and
      PPK) and pachyonychia congenita (PC). In this review, I describe the research
      that led to this discovery.

PMID- 9023701
TI  - Immunolocalization of epimorphin in skin.
AB  - Epimorphin was originally identified as a mesenchymal cell surface-associated
      protein that modulates epithelial morphogenesis in embryonic skin and lung
      epithelia. A previous report which utilized embryonic mouse skin, showed that
      epimorphin was localized non-homogeneously in a region adjacent to the epidermis
      and in a mesenchymal cell condensation located in front of growing hair
      follicles. We report herein a further detailed localization of this protein in
      adult mouse skin using immunoelectron microscopy. Epimorphin was found to be
      localized on the undersurface of basal cells, in the cytoplasm of cell processes
      of fibroblasts, as well as on the plasma membrane of fibroblasts, endothelial
      cells, pericytes, perineurium and endomysium. Our present finding indicated that
      epimorphin is one of the factors involved in multiple biological functions in a
      variety of structures derived from various origins and that it is not a specific
      epithelial morphogenetic factor.

PMID- 9023702
TI  - Healing of full-thickness wounds in pigs: effects of occlusive and non-occlusive
      dressings associated with a gel vehicle.
AB  - This study, based upon a pig model, was conducted to investigate the effects of
      moist and dry healing conditions on wound closure (epithelialization, granulation
      tissue, contraction) of full-thickness wounds. Thirty-two full-thickness square
      wounds (3 cm x 3 cm) covered with either an occlusive polyurethane dressing
      (Tegaderm) or a non-occlusive dressing (Melolin) were evaluated. The effect of
      the presence or the absence of a gel (3% Idroramnosan) was also investigated with
      both dressings. The dressings were renewed twice a week. The time required for
      wound closure was 19.2 +/- 1.6 days for Tegaderm and 26.6 +/- 3.0 days (means +/-
      SD) for Melolin, respectively. The healing time of the full-thickness porcine
      wounds was significantly (P < 0.001) reduced by the occlusive dressing.
      Equivalent results were found with the 3% gel, indicating that the gel can be
      used as a neutral vehicle. The healing rate, calculated according to Gilman's
      method, was also significantly (P < 0.001) enhanced by the occlusive dressing.
      This progression was 0.073 +/- 0.004 cm/day and 0.050 +/- 0.009 cm/day (means +/-
      SD) for Tegaderm and Melolin, respectively. The contribution of contraction to
      wound closure was similar in all wounds, indicating that the occlusive dressing
      did not have an effect on wound contraction. Histological evaluation was
      performed on full-thickness skin biopsies of whole wound harvested from the time
      of wound closure to 3 months after. At any time point, no significant
      histological variations were observed between the different treated wounds. This
      study demonstrates in a porcine model that for full-thickness wounds, as for
      split-thickness wounds, occlusive dressing enhances healing rate and shortens the
      time for wound repair. The shortened healing time is a function primarily of the
      effect of occlusive dressing on epithelialization, especially the third phase of
      wound resurfacing.

PMID- 9023703
TI  - Overlapping cases with psoriasis and Sjogren syndrome: a study of lymphocyte
      response to staphylococcal enterotoxin B.
AB  - Sjgren syndrome (SjS) is an auto-immune disease and immunological mechanisms have
      recently been suggested in the pathogenesis of psoriasis; however, co-existence
      of these diseases is relatively rare. To determine whether or not there exist the
      nature of common underlying abnormalities, five patients with psoriasis and SjS
      were studied. Two patients had psoriasis vulgaris (PV), two had psoriasis
      arthropathica (PA), and the other had generalized pustular psoriasis (GPP).
      Lymphocyte response against staphylococcal enterotoxin B was examined by 3H
      thymidine incorporation. In one patient with GPP, T-cell receptor (TCR) V beta
      repertoire of infiltrating T-cells into the lesional skin was examined by reverse
      transcriptase-polymerase chain reaction (RT-PCR). Stimulation index (S.I.) level
      of patients with psoriasis and SjS did not show any significant increases
      compared with patients with psoriasis or SjS alone; however, one patient with PV
      and SjS, who showed several serological immune imbalances, demonstrated a
      significant increase of S.I. level. Analysis of TCR V beta repertoire of the
      lesion of GPP showed strong expression of V beta 14 and 16 with mild expression
      of V 13-2 and 19, which may suggest that TCR V beta repertoire became oligoclonal
      in case of complication of these two disorders. In conclusion, our data did not
      suggest any common immunological responses to staphylococcal enterotoxin in
      induction of both psoriasis and SjS.

PMID- 9023704
TI  - Identification of K1/K10 and K5/K14 keratin pairs in human melanoma cell lines.
AB  - Keratin expression in cultured malignant melanoma cells has been studied only
      rarely. Moreover, no studies have reported of universality of keratin expression
      in human malignant melanoma cells. In this study, therefore, we analyzed keratin
      expression in eight cell lines. Using a low-salt aqueous solution without high
      salt and Triton X-100, as a washing buffer for keratin extraction, followed by
      two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and immunological
      analysis, we demonstrated keratin expression in all eight human malignant
      melanoma cell lines. The keratin polypeptide expressions common to all melanoma
      cells were K1, K5, K10 and K14. In addition, K8, K13, K17 and K18, respectively,
      were detected in individual cells. A measure of keratin expression universality
      in malignant melanoma cells may have implications regarding their invasive and
      metastatic behaviors, co-expressed with vimentin.

PMID- 9023705
TI  - Localization of monocyte chemotactic and activating factor (MCAF/MCP-1) in
      psoriasis.
AB  - The monocyte chemotactic protein-1 (MCAF) also termed MCP-1, a strong chemotactic
      factor towards monocytes, is produced by several cell types present in the skin.
      The in situ presence of MCAF/MCP-1 protein in the skin has, however, not yet been
      established. Using immunohistochemical techniques we have investigated the
      distribution of MCAF in skin from patients with different types of psoriasis and
      normal healthy volunteers. We report the novel finding that psoriasis has strong
      positive immunostaining for MCAF located to all the layers of the epidermis,
      except the stratum granulosum, in pustular, guttate and chronic plaque psoriasis.
      In the dermis, infiltrating cells in the perivascular aggregates and the blood
      vessels stained positive for MCAF. No significant differences were observed
      between the different subtypes of psoriasis except that strongly positive
      infiltrating cells were observed in the epidermal pustules in pustular psoriasis.
      In normals positive staining was observed in all the layers of the epidermis and
      in a few perivascular cells and blood vessels in the dermis. Where present in
      normal and diseased skin, eccrine ducts of sweat glands and sebaceous glands
      stained positive for MCAF. Arrector pili muscles were in all cases negative.
      These findings are consistent with a role for MCAF in attracting inflammatory
      cells, including monocytes, into the skin in psoriasis.

PMID- 9023706
TI  - Efficacy of Cafon gel on cutaneous infection with herpes simplex virus (HSV)-2
      and acyclovir-resistant HSV in mice.
AB  - Caffeine is known to inhibit replication of herpes simplex virus (HSV)-1 and the
      therapeutic efficacy of caffeine (Cafon) gel has been shown in a mouse model
      cutaneously infected with HSV-1. In this study we examined the inhibitory effect
      of caffeine on infection with HSV-2 and acyclovir-resistant HSV-1 strains,
      thymidine kinase (TK)-deficient and phosphonoacetic acid (PAA)-resistant HSV-1 in
      vitro and in vivo. Caffeine inhibited plaque formation of HSV-2 and acyclovir
      resistant HSV-1 strains and their EC50 values ranged from 0.42 to 1.11 mg/ml.
      Topical treatment with Cafon gel was significantly effective in retarding the
      development of skin lesions caused by cutaneous infection with HSV-2 and PAA
      resistant HSV-1 and in reducing the virus yield of the skin infected with TK
      deficient HSV-1. The results suggested that Cafon gel would be useful for the
      topical treatment of cutaneous infection with HSV-2 and acyclovir-resistant HSV
      strains.

PMID- 9023707
TI  - High blood pressure and end-organ damage.
AB  - BACKGROUND: Findings from numerous epidemiologic and clinical studies worldwide
      attest to a strong, graded, consistent relationship between blood pressure level
      and cardiovascular-renal diseases, subclinical and clinical, nonfatal and fatal.
      OBJECTIVE: This review summarizes results from selected prospective observational
      studies, primarily from US populations, and from randomized clinical trials.
      Review Analyses from the Multiple Risk Factor Intervention Trial (MRFIT) subjects
      (middle-aged men) and the Framingham Heart Study (middle-aged and elderly men and
      women) clearly establish that systolic blood pressure is a more powerful
      predictor of cardiovascular events than diastolic pressure. Wherever the full
      range of blood pressure has been examined, for example for systolic pressure in
      the MRFIT subjects and for diastolic pressure in pooled data from nine
      epidemiologic studies, the associations for coronary heart disease and stroke are
      seen to extend over the whole range, including 'normotensive' levels. In MRFIT,
      this continuous relationship has also recently been shown for end-stage renal
      disease and both systolic and diastolic pressure. Data from Framingham document
      further associations with peripheral vascular disease, congestive heart failure,
      and both electrocardiographic and echocardiographic left ventricular hypertrophy.
      Several studies are row available demonstrating a relationship between
      hypertension and carotid wall intimal-medial thickness. Finally, the causal
      nature of the relationships with major cardiovascular events is supported by the
      results of 17 large-scale randomized trials of blood-pressure-lowering using
      primarily diuretic- and beta-blocker-based drug regimens. CONCLUSIONS: These
      trials have demonstrated highly significant reductions in fatal and nonfatal
      stroke and major coronary heart disease. There are few trial data, however, on
      health benefits from further reducing blood pressure among normotensive persons.

PMID- 9023708
TI  - Twenty-four-hour blood pressure control: a brief review of aspects of target
      organ protection.
AB  - BACKGROUND: The increasing availability of ambulatory blood pressure monitoring
      has shifted interest in blood pressure measurement from the doctor's office to
      the entire 24-h period. Routine office blood pressure recordings correlate poorly
      with left ventricular mass, a sign of early target-organ damage. In contrast,
      ambulatory blood pressure or estimates of 24-h blood pressure load show a good
      correlation with left ventricular mass. STUDY FINDINGS: Circadian blood pressure
      rhythms may be important in determining future cardiovascular events. For
      example, patients who maintain high nocturnal blood pressures (non-dippers)
      experience more cardiovascular sequelae than do nocturnal dippers, with women non
      dippers having the greatest risk. Longer-acting antihypertensive drugs may return
      circadian blood pressure rhythms to normal by converting non-dippers to dippers.
      Adequate control of blood pressure toward the end of each 24-h cycle may reduce
      the early morning rise in cardiovascular events associated with awakening and
      ambulation. RECENT ADVANCES: Recent improvements in the estimation of trough to
      peak ratio have provided a useful arithmetic index for comparing the
      antihypertensive effects of different compounds over 24-h dosing intervals. Long
      acting agents have now been identified in each of the major classes of
      antihypertensive drugs, making it now possible to maximize target-organ
      protection by achieving good 24-h blood pressure control in most hypertensive
      patients.

PMID- 9023709
TI  - Renal protection and angiotensin converting enzyme inhibition in microalbuminuric
      type I and type II diabetic patients.
AB  - BACKGROUND: Many studies have emphasized the role of antihypertensive drugs and
      in particular angiotension converting enzyme (ACE) inhibitors in the retardation
      of diabetic nephropathy. Although these studies have focused predominantly on
      patients with overt proteinuria, more recently a number of investigators have
      explored the role of ACE inhibitors in both type I and type II diabetic patients
      with an earlier phase of diabetic renal disease known as microalbuminuria. These
      agents are now being considered as renoprotective agents not only in hypertensive
      patients but also in those with 'normal' blood pressure. Initially, studies in
      type I diabetic patients showed that ACE inhibition was effective in retarding
      the increase in albuminuria which was observed in placebo treated groups. More
      recently, several multi-centre placebo controlled studies have been performed
      suggesting that prolonged treatment not only reduced albuminuria but also
      preserved renal function. The role of ACE inhibition in microalbuminuric type II
      diabetic patients is less well characterised although several studies have
      recently described beneficial effects of ACE inhibition on albuminuria and
      possibly on renal function. REVIEW: Although ACE inhibitors have been clearly
      shown to reduce urinary albumin excretion in diabetic patients, the issue as to
      whether they confer a specific benefit over other classes of antihypertensive
      agents remains controversial. Several meta-analyses have suggested that ACE
      inhibitors are more potent at decreasing albuminuria or proteinuria than other
      antihypertensive agents, for a given reduction in blood pressure. The Melbourne
      Diabetic Nephropathy Study Group has instituted a study which is placebo
      controlled and is confined to normotensive type I and type II diabetic patients.
      The ACE inhibitor perindopril has been compared not only with placebo but also
      with the dihydropyridine calcium channel blocker, nifedipine. Preliminary
      analysis reveals that after 12 and 24 months of treatment, perindopril is more
      effective in reducing albuminuria than placebo or nifedipine. CONCLUSION: ACE
      inhibitors are a promising class of antihypertensive agents in diabetic patients
      with microalbuminuria. These drugs should be considered as first line agents in
      such patients, even in the absence of systemic hypertension.

PMID- 9023710
TI  - Clinical benefit of angiotensin converting enzyme inhibition after acute
      myocardial infarction: myocardial reperfusion revisited.
AB  - BACKGROUND: Beneficial effect has been reported from angiotensin converting
      enzyme (ACE) inhibition after acute myocardial infarction (AMI) in several
      experimental and large clinical studies showing improvements in haemodynamics,
      left ventricular remodelling and mortality. However, this benefit has not been
      prospectively evaluated after AMI effectively reperfused using current coronary
      recanalization techniques. CLINICAL ISSUE: The clinical relevance of reperfusion
      therapies including thrombolysis or percutaneous transluminal coronary
      angioplasty relates to their ability to limit infarct size and left ventricular
      dysfunction and reduce infarct-related morbidity and mortality. The clinical
      issue is to determine whether ACE inhibitors should be routinely proposed as an
      adjunct therapy in patients with a patent infarct-related vessel after AMI.
      RESULTS OF RECENT STUDIES: Three placebo-controlled randomized trials addressed
      this issue in evaluating the left ventricular remodelling process (i.e. left
      ventricular volumes and ejection fraction changes) during a 3 to 4-month follow
      up period. The Captopril and Thrombolysis Study and the Captopril plus Tissue
      plasminogen activator after Myocardial Infarction trials failed to show any
      significant preventive effect of early captopril therapy on remodelling in
      patients admitted for anterior AMI and treated with conventional use of
      streptokinase and alteplase, respectively. In the Salvage from Perindopril in
      Reperfused Infarction Trial, no beneficial effect on global left ventricular
      remodelling was observed from perindopril therapy in a population with effective
      myocardial reperfusion confirmed at angiography and moderately depressed left
      ventricular function. However, in this study ACE inhibition seemed to favourably
      alter remodeling in a subgroup of AMI patients with anterior location and large
      infarct size despite successful reperfusion. CONCLUSION: Recommendation for ACE
      inhibition as a routine adjunct therapy to reperfusion techniques is not
      supported by current data on short-term left ventricular function changes.

PMID- 9023711
TI  - Effects of angiotensin converting enzyme inhibition on vascular remodelling of
      resistance vessels in hypertensive patients.
AB  - BACKGROUND: Essential hypertension is known to be associated with a decrease in
      the lumen diameter and an increase in the wall thickness-to-lumen diameter ratio
      of the resistance vessels. Recently, it has been clarified that this alteration
      does not necessarily involve vascular growth, but could be due to a rearrangement
      of the same amount of material, a phenomenon now termed 'eutrophic remodelling'.
      OBJECTIVES: This review summarizes work aimed at determining the extent to which
      angiotensin converting enzyme (ACE) inhibitor treatment is able to normalize
      these abnormalities, and whether this is desirable. RESULTS: In essential
      hypertension, the changes seen in subcutaneous resistance vessels appear to be
      mainly due to eutrophic remodelling and only a small portion to growth. In
      addition, rat studies indicate that eutrophic remodelling, rather than growth, is
      found in all vascular beds. Antihypertensive treatment of hypertensive rats with
      ACE inhibitors causes a dose-dependent regression of the media: lumen ratio.
      Clinical studies have now confirmed these findings, showing that when previously
      untreated essential hypertensive patients are treated with the ACE inhibitor
      perindopril the abnormal structure of resistance vessels regresses towards normal
      values; in contrast, treatment with a beta-blocker does not affect the abnormal
      vascular structure. CONCLUSION: The available evidence indicates that ACE
      inhibitors are able to normalize the abnormal resistance vessel structure seen in
      essential hypertension, and suggests that this effect may not only be dependent
      on their ability to reduce blood pressure.

PMID- 9023712
TI  - Contribution of prevention to vascular cerebral disease management.
AB  - BACKGROUND: Epidemiological studies suggest that significant reductions in the
      incidence of stroke, as with coronary heart disease, can be expected by reducing
      the prevalence or shifting the distribution of risk factors across the entire
      population. Thus, identifying risk factors and intervening to control or modify
      them remains the most important means of further reducing the incidence and case
      fatality of stroke in developed countries, and controlling the emerging epidemic
      of cardiovascular disease in developing countries. All people should be
      encouraged to stop smoking, reduce weight, and increase physical activity and the
      consumption of fruit and vegetables. METHODS: The high-risk strategy involves the
      identification and management of people at high risk of developing stroke.
      Therapies of proven benefit in the prevention of stroke among certain individuals
      are blood pressure lowering therapy, antiplatelet therapy, anticoagulation
      therapy and carotid endarterectomy. Evidence is mounting that aggressive
      treatment of hypercholestrolaemia and hyperglycaemia is also effective in
      reducing the risk of stroke, but the role of aspirin and carotid endarterectomy
      in the primary prevention of stroke remains uncertain. This article will review
      strategies for the prevention of stroke, except blood pressure lowering therapy,
      which is discussed elsewhere, and address some of the questions about which
      individuals have the most to gain from various interventions.

PMID- 9023713
TI  - Perindopril treatment in the prevention of stroke in experimental animals.
AB  - OBJECTIVE: To determine the effect of perindopril treatment and treatment
      withdrawal in the prevention of stroke in male stroke-prone spontaneously
      hypertensive rats (SPSHR). DESIGN: After weaning at 4 weeks of age, male SPSHR
      were given a Japanese-style rat diet which induces stroke in these animals.
      Beginning at 6 weeks of age, SPSHR were treated with either distilled water
      (control) or different daily dosages of perindopril (1 or 4 mg/kg) by gavage for
      24 weeks followed by treatment withdrawal. Additional subgroups were treated with
      the 4 mg/kg dose for different durations (B, 12 or 24 weeks) before treatment
      withdrawal. Treatment effects on blood pressure, heart rate and body weight were
      studied during the treatment period and after the withdrawal of the treatment.
      Myogenic and mechanical properties of the middle cerebral arteries were studied
      in control SPSHR that had developed stroke, in treated SPSHR at the end of the
      treatment period, and at certain intervals after the withdrawal of the treatment.
      METHODS: Systolic blood pressure, heart rate and body weight of control and
      treated SPSHR were determined at regular intervals before, during and after the
      treatment withdrawal periods until they died from stroke, or until 42 or 43 weeks
      of age when the study was terminated. Functional studies of the cerebral arteries
      were carried out using a pressurized artery system. At necropsy, macroscopic and
      microscopic examinations were made of the kidneys and brain. RESULTS: Untreated
      SPSHR usually died of stroke-related complications by 14 weeks of age. The middle
      cerebral arteries from these animals had lost their ability to contract in
      response to pressure increase. Chronic treatment of SPSHR with perindopril when
      initiated at 6 weeks of age attenuated the sharp blood pressure rise, and
      prevented the development of stroke during the treatment period. This was
      associated with the preservation of the myogenic response of the middle cerebral
      arteries to pressure increase, and the prevention of tissue damage in the kidneys
      and brain. After withdrawal of the treatment, SPSHR treated for a longer period
      (12 or 24 weeks) also survived longer than those treated for a shorter period (8
      weeks). The subsequent loss of myogenic response in the middle cerebral arteries
      was associated with the development of stroke and death in these treatment
      withdrawal groups. CONCLUSION: Chronic treatment with perindopril is beneficial
      for the prevention of stroke in SPSHR, through the preservation of the myogenic
      response properties of the cerebral arteries, and the attenuation of tissue
      damage in the brain and kidneys.

PMID- 9023714
TI  - Blood pressure control after acute stroke.
AB  - BACKGROUND: Although long-term blood pressure control is known to prevent stroke,
      acute blood pressure reduction after stroke is associated with worse neurological
      and functional outcome. VASOACTIVE DRUG TREATMENT AFTER STROKE: Chronic blood
      pressure reduction for secondary prevention of stroke is presently being tested
      within the PROGRESS trial. This study uses angiotensin-converting enzyme (ACE)
      inhibitor-based treatment (perindopril) versus placebo. ACE inhibitors may reduce
      blood pressure without adversely affecting cerebral blood flow. We have recently
      reported elsewhere that perindopril 4 mg once daily, initiated within 2-7 days of
      acute ischaemic stroke, reduces blood pressure without adverse effects on
      cerebral blood flow as measured by Doppler ultrasound. Nevertheless, the optimal
      policy with regard to blood pressure management in the first 48 h after acute
      stroke remains uncertain. CONCLUSIONS: A clinical trial is proposed to establish
      whether it is better to maintain pre-existing antihypertensive therapy or to
      discontinue this temporarily.

PMID- 9023715
TI  - Blood pressure and the prevention of stroke.
AB  - RELATIONSHIP BETWEEN BLOOD PRESSURE AND STROKE: Data from prospective
      observational studies indicate that usual levels of blood pressure are directly
      and continuously related to the risk of initial stroke. A prolonged difference in
      usual blood pressure levels of just 9/5 mmHg is associated with approximately a
      one-third difference in stroke risk, with similar proportional effects in
      hypertensives and normotensives. Recent data from studies of individuals with a
      history of cerebrovascular disease indicate a similar association between blood
      pressure and the risk of recurrent stroke. EFFECTS OF TREATMENT ON STROKE: The
      results of randomized trials of blood pressure-lowering drugs in hypertensive
      patients suggest that much or all of the long-term potential stroke avoidance
      associated with prolonged blood pressure differences can be achieved within just
      a few years of beginning treatment. Overall, in 17 randomized trials of
      antihypertensive treatment a net blood pressure reduction of 10-12 mmHg systolic
      and 5-6 mmHg diastolic conferred a reduction in stroke incidence of 38% (SD 4),
      with similar reductions in fatal and non-fatal stroke. Because the proportional
      effects of treatment were similar in higher and lower risk patient groups, the
      absolute effects of treatment on stroke varied in direct proportion to the
      background risk of stroke. The greatest potential benefits were observed among
      those with a history of cerebrovascular disease; however, the results of the
      trials conducted in patients with a history of stroke or transient ischaemic
      attack, although promising, were not definitive. New trials are required to
      determine more reliably the effects of blood pressure lowering in patients with
      cerebrovascular disease.

PMID- 9023716
TI  - PROGRESS--perindopril protection against recurrent stroke study: status in July
      1996. PROGRESS Management Committee.
AB  - OBJECTIVES: The primary objective of PROGRESS is to determine reliably the
      efficacy of lowering blood pressure for the prevention of stroke in patients with
      a history of cerebrovascular disease. DESIGN: PROGRESS is a randomized, double
      blind, placebo-controlled trial investigating the effects on the incidence of
      stroke and other major cardiovascular events and dementia of treatment with the
      angiotensin-converting enzyme inhibitor perindopril, alone or in combination with
      the diuretic indapamide. METHODS: The study population comprises 6000
      normotensive or hypertensive patients with a history of stroke or transient
      ischaemic attack within the previous 5 years. The study is being conducted in
      over 160 centres in seven regions: Australia and New Zealand, The People's
      Republic of China, France and Belgium, Italy, Japan, Sweden and the United
      Kingdom. Computerized randomization to active treatment or placebo is performed
      by fax direct to Auckland, New Zealand. The primary study outcome is total stroke
      and secondary outcomes include fatal or non-fatal stroke, total major
      cardiovascular events and deaths, cognitive function and disability. Patients
      will be followed for a minimum of 4 years after randomization. RESULTS: By 16
      July 1996, 162 local clinical centres had been registered across the seven
      regions, and 1682 patients, 49% with a history of hypertension, had been randomly
      assigned to receive active treatment or placebo, with 65% allocated to the
      combination of perindopril and indapamide or double placebo, and 35% to
      perindopril alone or single placebo. Three months after randomization, the blood
      pressure difference between the treatment and control groups among the first 182
      patients randomized was 11.9 mmHg (systolic) and 3.9 mmHg (diastolic). Six
      strokes and two non-stroke cardiovascular deaths have been recorded after a total
      of 3174 patient-months of follow-up. CONCLUSIONS: Observations made so far
      confirm that full recruitment into the study is feasible and that treatment with
      perindopril and indapamide is well tolerated in the study population. The blood
      pressure differences between control and treatment groups recorded so far suggest
      that the study should have the power to achieve its primary objectives, provided
      compliance with treatment is satisfactory and 6000 patients are successfully
      recruited and followed for 4-5 years.

PMID- 9023717
TI  - Neural transmitter release: from quantal secretion to exocytosis and beyond. The
      Fenn Lecture.

PMID- 9023718
TI  - The morphology of synapses.

PMID- 9023719
TI  - Molecular mechanisms in synaptic vesicle recycling.

PMID- 9023720
TI  - Ultrastructural basis for gene expression at the synapse: synapse-associated
      polyribosome complexes.
AB  - This review summarizes what is known about the protein synthetic machinery that
      is selectively localized beneath postsynaptic sites on the dendrites of CNS
      neurons. This machinery, made up of polyribosomes and associated membranous
      cisterns, allows a local synthesis of key proteins at individual postsynaptic
      sites.

PMID- 9023721
TI  - Ultrastructure of synapses in the first-evolved nervous systems.
AB  - The phylum Cnidaria represents the first group of animals to evolve a
      recognizable nervous system. A comparison of the ultrastructural features of
      synaptic loci in animals representing all four classes of the cnidaria has
      provided an overview of the first-evolved synapses that can be compared
      morphologically to synapses in higher forms. Synapses in these watery jellylike
      animals with unmyelinated axons are sparse and difficult to fix well. However, we
      now have sufficient evidence to define an early synapse as one with paired
      electron dense plasma membranes separated by a 13-25 nm gap containing intracleft
      filaments and with vesicles on one or both sides of the synaptic cleft. The
      vesicles are of three types: dense-cored, clear, and opaque. Neuromuscular
      synapses resemble neuronal synapses and lack the postsynaptic specializations of
      higher animals. However, some coelenterates, such as the jellyfish Chrysaora,
      have a postsynaptic cisterna in the muscle. Neuromuscular and neuronematocyte
      synapses can have either clear or dense-cored vesicles. Opaque vesicles at two
      way interneuronal synapses and at neuromuscular synapses in the oral sphincter
      muscle of sea anemones can be labelled with antisera to the neuropeptides Antho
      RFamide (Antho-Arg-Phe-NH2) and Antho-RWamides (Antho-Arg-Trp-NH2) I and II,
      respectively. That suggests that neuropeptides evolved as neurotransmitters early
      in the animal kingdom. The basic differences between first evolved synapses and
      synapses of higher animals are the lack of postjunctional folds at neuromuscular
      synapses and the presence of fewer and somewhat larger synaptic vesicles,
      generally containing granular cores, in the more primitive animals.

PMID- 9023722
TI  - Genetic analysis of cholinergic nerve terminal function in invertebrates.
AB  - Genetic analysis of nerve terminal function is proving fruitful and studies on
      invertebrates are making a substantial impact. In this survey, particular
      emphasis has been placed on cholinergic chemical synaptic transmission. The
      advanced genetics of Drosophila melanogaster and Caenorhabditis elegans with
      their rich diversity of behavioural and biochemical mutants is providing new
      insights into the functions of key molecular components of synapses. A 'space
      invader' mutant of Periplaneta americana permits investigations of competition
      between neurons during synaptogenesis and its impact on neurotransmitter release.
      The growing importance of the C. elegans genome as a major research resource is
      emphasized in this survey.

PMID- 9023723
TI  - Reinnervation of frog sympathetic ganglia after selective denervation of B or C
      neurons.
AB  - Selective transection of the B or C preganglionic nerve fibres respectively
      innervating the B and C sympathetic neurons was carried out on the last two
      ganglia of the sympathetic chain of the frog Rana esculenta. At different times
      thereafter, the cross-reinnervation of one type of denervated neuron by nerve
      endings sprouting within the ganglia from intact fibres innervating the other
      type was investigated by both the quantitative morphology of the synaptic
      contacts and related structures and electrophysiological recordings of ganglionic
      transmission. As there are no fine ultrastructural criteria for distinguishing B
      from C neurons, the overall density of synapse, simple contact, and 'vacated'
      postsynaptic differentiation profiles was measured in the two cases of selective
      section and compared with the values for normal ganglia, therefore permitting the
      progress of cross-reinnervation with time for each type of neuron to be followed.
      At ten days after section of the C preganglionic fibres, immunocytochemistry
      showed that there were no anti-LH-RH-like peptide containing fibres within the
      ganglia. The B myelinated preganglionic fibres were able to reinnervate the
      denervated C neurons, with return to normal values of synaptic density and fully
      efficient transmission at two months in all tested C neurons. However, the
      latency of orthodromic action potentials was close to that of normally innervated
      B neurons. In contrast, the C non-myelinated preganglionic fibres reinnervated
      the denervated B neurons with limited efficiency, the synaptic density being two
      thirds the normal value after five months, while subthreshold excitatory
      postsynaptic potentials or action potentials were only recorded in 44% of the
      tested B neurons. The latency of these orthodromic responses was close to that of
      normally innervated C neurons. It is postulated that the poor cross-reinnervation
      of B neurons could be due to insufficient sprouting of C fibres and/or lack of
      'affinity' between C fibres and B neurons. In addition, these experiments
      demonstrated that the subsynaptic apparatus, fairly characteristic of frog
      ganglionic synapses, is present in both types of sympathetic neurons, although
      predominantly in B neurons.

PMID- 9023724
TI  - Synaptic dysplasia in sympathetic autonomic ganglia.

PMID- 9023725
TI  - How to count synapses unbiasedly and efficiently at the ultrastructural level:
      proposal for a standard sampling and counting protocol.
AB  - After almost 40 years, there is still no consensus on criteria for identifying
      different types of synapse seen in electron microscopical thin sections or on
      methods for counting them unbiasedly in 3D. This review proposes a procedure
      which meets these aims and could be adopted as a standard best-practice sampling
      and counting convention. It deals exclusively with unbiased stereological methods
      for counting particles in 3D space because these are efficient and applicable to
      arbitrary particles regardless of their size, shape and orientation. Methods
      based on individual sections are excluded because arbitrary particles cannot be
      counted unbiasedly with such sections. Model-based methods (e.g. treating
      synaptic membrane densities as circular disks) are excluded because they are not
      unbiased in general and now have limited (mainly historical) interest only. For
      unbiased counting, the absolute minimum requirement is a pair of parallel
      sections (dissector). The following protocol is recommended for future studies on
      synapse number: (1) use para(membrane) densities as synaptic counting units, (2)
      do not qualify definition of the counting unit by reference to a minimum number
      of synaptic vesicle profiles, (3) sample and count synapses unbiasedly using the
      dissector, and (4) in preference convert number per volume into absolute number
      or, in this is not possible, estimate a synapse-to-neuron ratio.

PMID- 9023726
TI  - Unbiased stereological estimation of the total number of synapses in a brain
      region.
AB  - Modern stereological methods have been used to make unbiased estimates of the
      total number of synapses in the striatum radiatum of the hippocampal CA1 region
      of five rabbits. The approach used involved a two stage analysis and is generally
      applicable to all parts of the nervous system. During the first stage of the
      analysis, the reference volume was estimated by point counting, at the light
      microscope level, according to the Cavalieri principle. During the second stage,
      the numerical density of synapses was estimated with dissectors at the electron
      microscopic level. The total number of synapses was calculated as the product of
      the numerical density and the volume of the region. The sampling with points and
      dissectors was carried out in all three dimensions of the entire CA1 region in a
      manner that ensured that all parts of the region and all synapses within it had
      equal probabilities of being sampled. An analysis of the precision of the
      estimate of total synapse number has been performed in terms of the variances of
      volume and synaptic numerical density at different levels of sampling, i.e. at
      the level of points, sections, individual animals and group of animals. Detailed
      descriptions of the procedures used to estimate the total number of synapses,
      evaluate the precision of the estimates, and optimize the sampling scheme are
      provided.

PMID- 9023727
TI  - Comparative evaluation of synaptophysin-based methods for quantification of
      synapses.
AB  - Development, ageing, and a variety of neurological disorders are characterized by
      selective alterations in specific populations of nerve cells which are, in turn,
      associated with changes in the numbers of synapses in the target fields of these
      neurons. To begin to delineate the significance of changes in synapses in
      development, ageing, and disease, it is first essential to quantify the number of
      synapses in defined regions of the CNS. In the past, investigators have used EM
      methods to assess synapse numbers or density, but these approaches are costly,
      labour intensive, and technically difficult, particularly in autopsy material. To
      begin to define reliable strategies useful for studies of both animals and
      humans, we used three techniques to measure synaptophysin-immunoreactivity in rat
      brain. The levels of synaptophysin protein were determined by Western blots of
      five hippocampal subregions; the intensity of synaptophysin-immunoreactivity in
      dentate gyrus and stratum oriens was determined by optical densitometry of
      immunocytochemically stained sections; and the total number of synaptophysin
      immunoreactivity presynaptic boutons in dentate gyrus and stratum oriens was
      assessed by unbiased stereology. Each approach has advantages and disadvantages.
      Western blotting is the least time-consuming of the three methods and allows
      simultaneous processing of multiple samples. In systematically sampled
      histological sections, both densitometry and stereology allow precise definition
      of the region of interest, and the stereological optical dissector method allows
      quantitation of the numbers of synaptophysin-immunoreactive boutons. Stereology
      was the only method that clearly demonstrated greater synaptophysin
      immunoreactivity in the dentate gyrus as compared to stratum oriens. The use of
      systematic sampling and the dissector technique offer a high degree of anatomical
      resolution (lacking in Western blot methods) and has quantitative advantage over
      the greyscale-based density approach. Thus, at present, stereology is the most
      useful method for estimating synaptic numbers in defined regions of the brain.

PMID- 9023728
TI  - Cerebellar choline acetyltransferase positive mossy fibres and their granule and
      unipolar brush cell targets: a model for central cholinergic nicotinic
      neurotransmission.
AB  - A subset of cerebellar mossy fibres is rich in choline acetyltransferase, the
      rate-limiting enzyme for the synthesis of acetylcholine. These choline
      acetyltransferase-positive mossy fibres are concentrated in the
      vestibulocerebellum and originate predominantly from the medial vestibular
      nucleus. The granular layer of the vestibulocerebellum is also enriched in
      unipolar brush cells, an unusual type of small neuron that form giant synapses
      with mossy fibres. In this immunocytochemical light and electron microscopic
      study, we explored whether choline acetyltransferase-positive mossy fibres
      innervate unipolar brush cells of the rat cerebellum. We utilized monoclonal
      antibodies to rat choline acetyltransferase of proven specificity, and
      immunoperoxidase procedures with 3,3'-diaminobenzidine tetrahydrochloride as the
      chromogen. A high density of choline acetyltransferase-positive fibres occurred
      in the nodulus and ventral uvula, where they showed an uneven, zonal
      distribution. Immunostained mossy fibre rosettes contained high densities of
      round synaptic vesicles and mitochondria. They formed asymmetric synaptic
      junctions with dendritic profiles of both granule cells and unipolar brush cells.
      The synaptic contacts between choline acetyltransferase-immunoreactive mossy
      fibres and unipolar brush cells were very extensive, and did not differ from
      synapses of choline acetyltransferase-negative mossy fibres with unipolar brush
      cells. Analysis of a total area of 1.25 mm2 of the nodulus from three rats
      revealed that 14.2% of choline acetyltransferase-immunoreactive mossy fibre
      rosettes formed synapses with unipolar brush cells profiles. Choline
      acetyltransferase-positive rosettes accounted for 21.7% of the rosettes forming
      synapses with unipolar brush cells. Thus, the present data demonstrate that
      unipolar brush cells are innervated by a heterogeneous population of mossy
      fibres, and that some unipolar brush cells receive cholinergic synaptic input
      from the medial vestibular nucleus. The ultrastructure of these synapses is
      compatible with the possibility that choline acetyltransferase-positive mossy
      fibres co-release acetylcholine and glutamate. As the granular layer of the
      vestibulocerebellum contains nicotinic binding sites, the choline
      acetyltransferase-positive mossy fibres may be a model for studying nicotinic
      neurotransmission in the CNS.

PMID- 9023729
TI  - Ultrastructural view of central catecholaminergic transmission:
      immunocytochemical localization of synthesizing enzymes, transporters and
      receptors.

PMID- 9023730
TI  - Functional consequences of changes in NMDA receptor subunit expression during
      development.

PMID- 9023731
TI  - Neuromuscular transmission at an active zone: the secretosome hypothesis.

PMID- 9023732
TI  - The role of synapses in cortical computation.
AB  - The synapse, first introduced as physiological hypothesis by C.S. Sherrington at
      the close of the nineteenth century, has, 100 years on, become the nexus for
      anatomical and functional investigations of interneuronal communication. A number
      of hypotheses have been proposed that give local synaptic interactions specific
      roles in generating an algebra or logic for computations in the neocortex.
      Experimental work, however, has provided little support for such schemes.
      Instead, both structural and functional studies indicate that characteristically
      cortical functions, e.g., the identification of the motion or orientation of
      objects, involve computations that must be achieved with high accuracy through
      the collective action of hundreds or thousands of neurons connected in recurrent
      microcircuits. Some important principles that emerge from this collective action
      can effectively be captured by simple electronic models. More detailed models
      explain the nature of the complex computations performed by the cortical circuits
      and how the computations remain so remarkably robust in the face of a number of
      sources of noise, including variability in the anatomical connections, large
      variance in the synaptic responses and in the trial-to-trial output of single
      neurons, and weak or degraded input signals.

PMID- 9023733
TI  - Differential expression of NGFI-B and RNR-1 genes in various tissues and
      developing brain of the rat: comparative study by quantitative reverse
      transcription-polymerase chain reaction.
AB  - NGFI-B and RNR-1 are closely related transcription factors that constitute a
      distinct subclass within the steroid/thyroid hormone receptor superfamily. They
      have been implicated in neuronal differentiation, neuroendocrine regulation of
      adrenocortical function and T-cell apoptosis. In this study, we measured and
      compared NGFI-B and RNR-1 mRNA levels in various adult rat tissues and in the
      developing rat brain by means of the quantitative reverse transcription
      polymerase chain reaction. The use of RNA standards synthesized in vitro allowed
      direct comparison of the amount of the transcripts of these two genes. We
      demonstrated that the transcripts of both genes were present in all tissues
      examined although the expression levels widely varied. We found the highest
      constitutive expression of both genes in the pituitary. High levels of NGFI-B
      were also expressed in the cerebral cortex, muscle, ventral prostate, thymus and
      adrenal glands, whereas high levels of RNR-1 expression were restricted to the
      pituitary and cerebral cortex. These findings were consistent with the notion
      that NGFI-B and RNR-1 are involved in various signal transduction systems in
      diverse cell types. The amount of NGFI-B mRNA was greater than that of RNR-1 mRNA
      in all adult rat tissues, with the highest ratio of NGFI-B relative to RNR-1
      expression in the muscle and leukocytes. In contrast, fetal rat brain showed
      relatively high RNR-1 gene expression. These findings suggested that the NGFI-B
      and RNR-1 genes are differentially expressed in a tissue-specific and
      developmentally regulated manner.

PMID- 9023734
TI  - The milk-ejection reflex in the peri-partum rat: effects of oestradiol and
      progesterone on basal milk-ejection frequency and the facilitatory response to
      central oxytocin.
AB  - Experiments were undertaken to examine the effects of ovarian steroids on the
      functional characteristics of the milk-ejection reflex during late pregnancy.
      Basal milk-ejection frequency and response to i.c.v. oxytocin (OT) were compared
      in different experimental groups, using intramammary pressure recordings obtained
      in suckling tests under urethane anaesthesia. Ovariectomy (OVX) on day 20 of
      pregnancy significantly (P < 0.05) increased milk-ejection frequency on day 22,
      compared with sham-OVXed animals. I.c.v. injection of 2.2 ng OT during suckling
      had no consistent effect on milk ejection in either of these groups. Pretreatment
      with oestradiol (5 micrograms per day, s.c.) or progesterone (5 mg per day, s.c.)
      both resulted in a fall in milk-ejection frequency compared to oil-treated OVXed
      controls. However, whereas oestradiol-treated OVXed rats showed a facilitatory
      response to i.c.v. OT, with a significant (P < 0.05) increase in milk-ejection
      frequency in the 20 min period after injection, progesterone-treated OVXed rats
      showed only a delayed decrease in milk-ejection frequency (significant at P <
      0.05 between 20-40 min after injection). Oil-treated OVXed rats showed no
      significant response to i.c.v. OT at any stage. Electrophysiological recordings
      from supraoptic OT neurones confirmed that bursting activity was increased by
      i.c.v. injection of OT in oestradiol-treated, but not progesterone-treated rats.
      Further experiments with hysterectomized ovariectomized rats indicated that the
      difference in response to i.c.v. OT in oestradiol- vs progesterone-treated rats
      was not related to changes in the timing of birth induced steroid treatments.
      These findings demonstrate the ability of ovarian steroids to alter the
      characteristics of the milk-ejection reflex in the peri-partum rat. In
      particular, the rise in oestradiol and fall in progestesterone near term, may
      contribute to programming of the facilitary response to central OT in preparation
      for lactation.

PMID- 9023735
TI  - The noradrenergic innervation of identified hypothalamic magnocellular somata and
      its contribution to lactation-induced synaptic plasticity.
AB  - Despite several studies showing that the rat supraoptic (SON) and paraventricular
      (PVN) nuclei are innervated by noradrenergic afferents, the respective
      contribution of these inputs to the oxytocinergic and vasopressinergic neuronal
      populations remains to be clearly defined. In the present study, we used the
      unbiased disector method to estimate the numerical density of noradrenergic
      varicosities on identified oxytocinergic and vasopressinergic somata in the rat
      SON and PVN. The analysis was carried out on semithin (1 micron) plastic sections
      cut from vibratome slices (50 microns) of the SON and PVN which had been double
      labelled for noradrenaline (NA) and oxytocin- or vasopressin-related neurophysin.
      These preparations displayed many noradrenergic varicosities which electron
      microscopy showed to represent, in the main, synaptic boutons. Our quantitative
      analysis revealed that noradrenergic varicosities contacted oxytocinergic and
      vasopressinergic somata to a similar extent in male and female rats, under basal
      conditions of hormone secretion. The incidence of these axo-somatic contacts was
      similar in the SON and PVN. In contrast, in lactating rats, in which oxytocin
      secretion is enhanced, there was a significant increase in the density of
      noradrenergic varicosities apposed to oxytocinergic somata, in both nuclei. Our
      observations indicate that, in male and female rats under normal conditions,
      noradrenergic afferents innervate each type of neurosecretory somata, in both
      magnocellular nuclei, in a similar fashion. They reveal, moreover, that
      noradrenergic afferents participate in lactation-induced structural plasticity of
      synapses impinging on oxytocinergic somata.

PMID- 9023736
TI  - Immunotargeted lesions of paraventricular CRF and AVP neurons in developing rats
      reveal the pattern of maturation of these systems and their functional
      importance.
AB  - Pituitary ACTH secretion in the rat is controlled by a number of hypothalamic
      secretagogues, like CRF and AVP and by inhibitory feedback provided by
      glucocorticoids. During development, little is known about the precise regulation
      of ACTH release by hypothalamic neuropeptides and glucocorticoids. We used
      immunotargeted chemical PVN lesions to investigate the role of CRF and AVP
      neurons of the hypothalamic paraventricular nucleus (PVN) in the control of ACTH
      secretion in neonatal rats under basal conditions and 5 days after adrenalectomy
      (ADX). Neonates aged day (d) 4 or d14 were injected over the PVN with ricin A
      toxin associated with either non-specific antibodies (IgG/Tx), or monoclonal
      antibodies directed towards CRF (CRF/Tx) or AVP (AVP/Tx). Rats from each group
      received either sham surgery (SHAM) or were adrenalectomized (ADX). Pups were
      sacrificed 5 days after PVN treatment and adrenal surgery (d9 or 19). Plasma ACTH
      and corticosterone (B) levels were measured by RIAs. Changes in CRF and AVP
      expression in the PVN and other brain regions were determined by
      immunohistochemistry (ICC) and in situ hybridization. Injection of the toxin
      associated with IgGs did not have non specific effects on body weight gain,
      neuropeptide expression or plasma ACTH and B secretion compared to intact,
      uninjected rats. Lesions of CRF or AVP neurons greatly reduced peptide expression
      and mRNA levels in the PVN and median eminence at both ages. However, the
      specificity of the lesion was greater in older than in young pups. At both ages,
      we observed a dissociation between the morphological effects of the lesions and
      hormonal responses. In d14-19 pups, CRF and AVP lesions prevented ADX-induced
      changes in mRNA levels and peptide expression but did not reduce ACTH secretion
      under basal or stimulated (post ADX) conditions. However, CRF and AVP lesions
      increased the expression of CRF in the central amygdala and the bed nucleus of
      the stria terminalis. Lesions with AVP also stimulated CRF expression in the PVN.
      Thus, these compensatory changes could take over some of the hypophysiotropic
      actions of the damaged PVN neurons. In young pups (d4-9), we did not observe the
      typical increase in CRF and AVP mRNA levels and peptide expression found after
      ADX in older pups or adults. Lesions of the CRF neurons also affected the AVP
      system and reciprocally. We suggest that this could be explained by a high degree
      of colocalization of CRF and AVP observed in parvocellular and small, immature
      magnocellular neurons in young pups. The lesions did not affect basal or ADX
      induced ACTH secretion, suggesting that during the early neonatal period, the
      pituitary is the major site of glucocorticoid inhibitory feedback on ACTH
      secretion and that the hypothalamus does not exert a tonic control over basal
      pituitary secretion. These results unravel ontogenetical differences in the
      regulation of ACTH secretion by hypothalamic CRF and AVP. During the first 10
      days of life, within the adrenal stress hyporesponsive period, hypothalamic CRF
      and AVP neurons are not sensitive to glucocorticoid feedback and basal ACTH
      secretion appears to be relatively independent from hypothalamic input. After the
      second week of life, maturation of glucocorticoid receptors, neuronal phenotype
      and connections of the PVN to other brain structures (bed nucleus of the stria
      terminalis, central amygdala) allows for the full expression of corticosterone
      effect on hypothalamic neurons and for compensatory changes to occur following
      lesions. These results emphasize the extraordinary capacity of the developing
      central nervous system to adapt to changes in functionning of some neuronal areas
      critical for homeostatic balance and the important potential role of intra
      hypothalamic and extrahypothalamic relationships in maintaining control over ACTH
      and glucocorticoid production during development.

PMID- 9023737
TI  - Heterogeneity of pituitary folliculo-stellate cells: implications for interleukin
      6 production and accessory function in vitro.
AB  - The population of folliculo-stellate (FS) cells of the rat anterior pituitary has
      been shown to be ultrastructurally and immunohistochemically heterogeneous. Based
      on the overlap of ultrastructural characteristics, the localization in the
      anterior pituitary and the co-expression within the same cel of the S-100 protein
      (a marker for FS cells) and MHC-class II determinants (an immune marker) we
      concluded that a partial overlap exists between the population of FS cells and
      the monocyte-derived dendritic cells (DC). In this report we describe that
      interleukin-6 (IL-6) immunoreactivity was found in situ in stellate cells of the
      rat, mouse and human anterior pituitary at a very low density (< 1% of the
      cells); the topography was reminiscent of the distribution of FS cells. In the
      present study we also analyse three different pituitary cell separation methods,
      in order to study the functional heterogeneity of the FS cells in vitro, and to
      verify whether functionally distinct subpopulations exist within the FS cell
      group. Production of bioactive IL-6 was measured in conditioned media of rat
      anterior pituitary cells separated by (i) bovine serum albumin (BSA) gradient
      sedimentation at 1 g, (ii) Nycodenz gradient and (iii) a magnetic cell separation
      (MACS) technique. Production of bioactive IL-6 by cell cultures of 1 to 4 days
      was correlated with the proportional number of S100 immunoreactive and S100
      producing cells, but was not correlated with the proportional number of MHC-class
      II expressing (OX6-positive) dendritic cells (DC). The distribution pattern of
      OX6-positive DC was found to partly overlap with the distribution pattern of S100
      positive cells in the BSA gradient. Co-sedimentation of S100-positive FS cells
      and MHC-class II-expressing DC was not restricted to the top fractions of the BSA
      gradient, but was also found in the low density Nycodenz fraction. MACS
      separation of the rat anterior pituitary cells resulted into a population
      enriched in OX6 and OX62 positive DC and a population devoid of such cells, while
      S100+ cells were equally divided into these two subpopulations. Although there
      was a significantly decreased production of IL-6 as compared to that of an
      original pituitary cell population, both MACS separated populations were equal in
      IL-6 production. The diminution in IL-6 production in both populations may be the
      result of an impediment of paracrine communication due to the MACS separation
      into these two populations. Our data also show that a subpopulation of FS cells
      was capable of stimulating T cell proliferation in vitro. Concomitantly with the
      distribution pattern of S100- and OX6-immunoreactive cells in the BSA and
      Nycodenz gradient fractions, we found a similar pattern of stimulation of T cell
      proliferation. Unlike the IL-6 production pattern, the T cell stimulating
      capacity was present in the MHC-class II-enriched cell population but absent in
      the MHC-class II-depleted cell population. These findings-together with earlier
      in situ histochemical data-suggest that there is an OX6+ S100- subpopulation of
      FS cells in the anterior pituitary that in itself is capable of stimulating T
      cell proliferation in vitro, and acts as lymphoid DC. There is also an S100+ OX6-
      population that is unable to stimulate T cell proliferation in vitro. Both
      populations are able to produce IL-6, but probably need stimuli from other
      subpopulations of pituitary cells (or exogeneous stimuli) to produce maximal
      amounts of IL-6.

PMID- 9023738
TI  - Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y
      gene expression induced by zinc deficiency in the rat.
AB  - Dietary zinc-deficiency induces a striking reduction and a cyclic pattern of food
      intake in rodents. To elucidate the mechanisms for these effects, we studied the
      hypothalamic content, synthesis, and distribution of galanin (GAL) and
      neuropeptide Y (NPY) during zinc deficiency and refeeding in the rat. In Wistar
      rats, three weeks of zinc-deprivation consistently induced a reduction and a
      cyclic pattern of night- and day-time food intake, as well as of water intake.
      This was accompanied in zinc-deficient (ZD) rats, and to a lesser extent in pair
      fed (PF) rats, by a decrease of hypothalamic GAL mRNA concentration (CTR: 100 +/-
      8, ZD: 61 +/- 4, PF: 78 +/- 2 arbitrary densitometric units, ADU, P < 0.01) and
      an increase of hypothalamic NPY (CTR: 100 +/- 11, ZD: 154 +/- 10, PF: 126 +/- 4
      ADU, P < 0.05), without peptide modification. The two neuropeptidergic systems
      were not affected by the cycles of feeding, with the exception of the NPY
      immunoreactivity in the suprachiasmatic nuclei (geniculo-hypothalamic tract),
      that was inversely correlated to the food intake in both ZD and PF animals. In a
      second experiment, we showed that zinc-repletion for 4 days suppressed the
      behaviour induced by a two-week zinc-deprivation, and reversed the increase of
      NPY mRNA in ZD animals. We finally demonstrated that zinc-deficiency induced a
      similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY
      is constitutively up-regulated, no change of NPY synthesis was observed in ZD
      rats, suggesting that the increase observed in Wistar is adaptative rather than
      instrumental to the abnormal food intake. In conclusion, we have further
      characterized the cyclic feeding behaviour of the zinc-deficient Wistar rats, and
      shown in these animals a decreased activity of the GAL system and an increased
      activity of the NPY system, likely corresponding to a compensatory response of
      the two neuropeptidergic systems, as observed in food-deprived animals. As
      spontaneous food intake of ZD rats does not increase, a resistance to NPY could
      also be present. These behavioural and neuropeptidergic changes were partially
      reversed by reintroduction of zinc in the diet. In Zucker rats, the same
      behaviour occurred despite an insensitivity of the NPY system to the zinc
      deficiency. In addition, we describe a nutritional regulation of the NPY
      immunoreactivity in the geniculo-hypothalamic tract, that could constitute the
      substrate of circadian rhythm modulation by timed feeding.

PMID- 9023739
TI  - Osmotic modulation in glutamatergic excitatory synaptic inputs to neurons in the
      supraoptic nucleus of rat hypothalamus in vitro.
AB  - To clarify influence of osmotic stimulation on the excitatory synaptic inputs to
      the neurosecretory cells of the supraoptic nucleus (SON), the blind patch
      technique was used in rat hypothalamic slice preparations. Stable whole-cell
      recordings were made from 22 neurons in the SON. To observe spontaneous
      excitatory postsynaptic currents (sEPSCs) in the SON neurons, membrane potentials
      were clamped between -50 and -90mV. The effects of hypertonic stimulation on the
      frequency of the sEPSCs were tested in 18 SON neurons. Bath application of
      mannitol 30 or 60 mM increased the frequency of the sEPSCs. During the
      application of mannitol (60 mM), the frequency of the sEPSCs increased in 12 of
      15 neurons without a change in amplitude. Hypertonic stimulation with NaCl (30
      mM) had similar effects to that of mannitol. The increased frequency of miniature
      EPSCs (mEPSCs) during mannitol application persisted in the presence of TTX in
      all 8 SON neurons tested with no change in amplitude. Both the non-NMDA
      antagonist CNQX at 10-30 microM (n = 6) and the non-selective glutamate
      antagonist kynurenic acid at 1 mM (n = 3) almost completely blocked the EPSCs
      while the NMDA antagonist AP-5 at 10 microM had no effect on the frequency of the
      EPSCs in the 4 neurons tested. During application of CNQX, mannitol (60 mM) was
      added to the perfusion medium in 3 SON neurons. Under these conditions, mannitol
      had no effect on the frequency of EPSCs. We conclude that hypertonic stimulation
      directly influences glutamatergic inputs to the neurosecretory cells of the SON
      by an action on the presynaptic terminals and enhances the excitatory synaptic
      events.

PMID- 9023740
TI  - Transient suppression of resting corticosterone levels induces sustained increase
      of AVP stores in hypothalamic CRH-neurons of rats.
AB  - Previous studies showed that various stressors can induce delayed (days) and long
      lasting (weeks) increases of vasopressin (AVP) stores in terminals of CRH neurons
      in the external zone of the median eminence (ZEME) in adult rats. Here we tested
      whether this long-lasting neuroplastic change can be induced by mechanisms other
      than stressor provoked transsynaptic activation of CRH neurons. Single i.v.
      administration of a CRH antibody to adult rats causes a delayed (at least 1 day)
      and long-lasting (3 weeks) increase (2-3 fold) of AVP stores in the ZEME without
      affecting CRH stores. It suppresses ether-induced ACTH-responses for at least 8
      days. In contrast, resting pm levels of ACTH and corticosterone (CORT) were
      suppressed only during the first 2 days. Suppletion of CORT levels on day 1 and
      2, attenuates the antibody induced AVP-increase by 57%. CRH-immunoneutralization
      did not affect the AVP stores in CORT supplemented ADX rats. Thus, long-term
      increases of AVP stores induced by CRH-immunoneutralization largely depend on
      short-term suppression of pm CORT levels. Accordingly, single administration of
      metyrapone, which causes a transient suppression of pm CORT levels, increases AVP
      (1.5 fold) but not CRH stores one week later. We conclude that transient
      activation of hypothalamic CRH neurons results in long-lasting increases in AVP
      co-expression irrespective of the nature of the activating stimulus.

PMID- 9023763
TI  - Properties of cloned KATP channels mimic those of beta-cells.

PMID- 9023764
TI  - Cross-bridge detachment and attachment following a step stretch imposed on active
      single frog muscle fibres.
AB  - 1. The time course of cross-bridge detachment-attachment following a step stretch
      was determined in single frog muscle fibres (at 4 degrees (1 and 2.1 microns
      sarcomere length) by imposing, under sarcomere length control by a striation
      follower, test step releases of various amplitudes (2-13 nm per half-sarcomere)
      at successive times (4-55 ms) after a conditioning stretch of approximately 4 nm
      per half-sarcomere. 2. The comparison with the control tension transients,
      elicited by releases not preceded by the conditioning stretch, shows that, early
      after the conditioning stretch, the quick tension recovery following small
      releases is depressed and the quick tension recovery following large releases is
      potentiated. Both effects are expected as a consequence of the strain produced in
      the cross-bridges by the conditioning stretch. 3. These effects disappear and the
      tension transient is reprimed, indicating substitution of freshly attached cross
      bridges for strained cross-bridges, with a time constant of approximately 10 ms.
      4. A novel multiple-exponential equation, based on the hypothesis of complete
      substitution of freshly attached cross-bridges for the cross-bridges that
      underwent the stretch, has been used to fit the whole tension transient following
      step stretches of different sizes (2-6 nm per half-sarcomere). For a stretch of 4
      nm, the time constant of the exponential process responsible for cross-bridge
      detachment (tau d, 9.3 ms) almost coincides with the time constant of repriming
      as measured by the double-step experiments. The time constant of the exponential
      process representing the cumulative effects of attachment and force generation
      (tau 3) is 13.6 ms. 5. For stretches of different sizes the amount of quick
      tension recovery attributable to the reversal of the working stroke elicited by
      the stretches is estimated by subtracting, from the original tension transient,
      the contribution to tension recovery due to detachment-attachment of cross
      bridges as estimated by the multiple-exponential analysis. Following this
      calculation, the structural change in the myosin heads responsible for the
      reversal of the working stroke can be 2 nm at maximum, suggesting that the
      elastic component in the cross-bridges is at least twice as rigid as previously
      thought.

PMID- 9023765
TI  - Effects of reduced muscle glycogen concentration on force, Ca2+ release and
      contractile protein function in intact mouse skeletal muscle.
AB  - 1. The purpose of this study was to examine the effects of reduced glycogen
      concentration on force, Ca2+ release and myofibrillar protein function during
      fatigue in skeletal muscle. Force and intracellular free Ca2+ concentration
      ([Ca2+]i) were measured in single mammalian skeletal muscle fibres during fatigue
      and recovery. Glycogen was measured in bundles of 20-40 fibres from the same
      muscle under the same conditions. 2. Fatigue was induced by repeated maximum
      tetani until force was reduced to 30% of initial. This was associated with a
      reduction in muscle glycogen to 27 +/- 6% of control values. In fibres allowed to
      recover for 60 min in the presence of 5.5 mM glucose (n = 6), tetanic (100 Hz)
      force recovered fully but tetanic [Ca2+]i remained at 82 +/- 8% of initial
      values. This prolonged depression in Ca2+ release was not associated with
      decreased muscle glycogen since glycogen had recovered to pre-fatigue levels (157
      +/- 42%). 3. To examine the responses under conditions of reduced muscle glycogen
      concentration, fibres recovered from fatigue for 60 min in the absence of glucose
      (n = 6). After glucose-free recovery, the decreases in tetanic force and [Ca2+]i
      were only partially reversed (to 64 +/- 8% and 57 +/- 7% of initial values,
      respectively). These alterations were associated with a sustained reduction in
      muscle glycogen concentration (27 +/- 4% of initial values). 4. In another set of
      fibres, fatigue was followed by 50 Hz intermittent stimulation for 22.6 +/- 4
      min. With this protocol, tetanic force and [Ca2+]i partially recovered to 76 +/-
      9% and 55 +/- 6% of initial levels, respectively. These changes were associated
      with a recovery of muscle glycogen (to 85 +/- 10%). 5. During fatigue, Ca2+
      sensitivity and maximum Ca(2+)-activated force (Fmax) were depressed but these
      alterations were fully reversed when muscle glycogen recovered. When glycogen did
      not recover, Ca2+ sensitivity remained depressed but Fmax partially recovered.
      The altered myofibrillar protein function is probably due to alterations in
      inorganic phosphate levels or other metabolites associated with reduced levels of
      muscle glycogen. 6. These data indicate that the reductions in force, Ca2+
      release and contractile protein inhibition observed during fatigue are closely
      associated with reduced muscle glycogen concentration. These findings also
      suggest that the changes in Ca2+ release associated with fatigue and recovery
      have two components-one which is glycogen dependent and another which is
      independent of glycogen but depends on previous activity.

PMID- 9023766
TI  - Mitochondria accumulate Ca2+ following intense glutamate stimulation of cultured
      rat forebrain neurones.
AB  - 1. In cultures of rat forebrain neurones, mitochondria buffer glutamate-induced,
      NMDA receptor-mediated Ca2+ influx. Here, we have used the fluorescent calcium
      indicator, indo-1 AM to record [Ca2+]i from single cells. We varied either the
      glutamate concentration or the duration of exposure to investigate the cellular
      mechanisms recruited to buffer [Ca2+]i within different stimulation protocols. 2.
      For a 15 s stimulus, the recovery time doubled as the glutamate concentration was
      raised from 3 to 300 microM. Changing the duration of exposure from 15 s to 5 min
      increased the recovery time tenfold even when the glutamate concentration was
      held at 3 microM. 3. We used a selective inhibitor of the mitochondrial Na(+)
      Ca2+ exchange, CGP-37157. When applied immediately after a 15 s, 100 microM
      glutamate challenge, CGP-37157 consistently caused a rapid fall in [Ca2+]i
      followed by a slow rise after the drug was washed out. A similar pattern was seen
      with the 5 min, 3 microM glutamate stimulus. The effects of CGP-37157 are
      consistent with the release of substantial mitochondrial Ca2+ stores during
      recovery from an intense glutamate stimulus. 4. These studies suggest that
      mitochondria become progressively more important for buffering glutamate-induced
      Ca2+ loads as the stimulus intensity increases. The recovery of [Ca2+]i to
      baseline following glutamate removal is critically regulated by the release of
      Ca2+ from mitochondrial stores via mitochondrial Na(+)-Ca2+ exchange. The data
      highlight a previously under-appreciated role for [Na+]i in the regulation of
      [Ca2+]i in central neurones.

PMID- 9023767
TI  - Intracellular pH and calcium in frog early distal tubule: effects of transport
      inhibitors.
AB  - 1. The K+ channels of the apical membrane of the diluting segment (early distal
      tubule, EDT) of the frog are involved in the regulation of transepithelial NaCl
      transport. These channels are sensitive to pHi and intracellular Ca2+ (Ca2+i).
      Inhibition of transport by furosemide (frusemide) results in a compensatory
      increase in K+ channel activity. The aims of the present study were to determine
      whether pHi or Ca2+i were altered by furosemide, and to identify the means by
      which such changes were brought about. 2. Experiments were performed using
      single, microperfused EDT segments. Measurements of pHi and Ca2+i were made using
      the intracellular fluorescent probes, 2',7'-bis(carboxyethyl)-5,6
      carboxyfluorescein (BCECF) and fura-2, respectively. 3. Furosemide increased pHi
      and Ca2+i. The intracellular alkalinization was the result of an alkaline shift
      in the set-point of the basolateral Na(+)-H+ exchanger. This response was
      dependent upon the increase in Ca2+i. 4. The increase in Ca2+i produced by
      furosemide was due to the release of Ca2+ from intracellular stores. Depletion of
      these stores, by 2,5-di-t-butylhydroquinone (TBQ) and caffeine, prevented the
      furosemide-induced changes in Ca2+ and pH. 5. Furosemide-induced activation of
      Na(+)-H+ exchange was prevented by the calmodulin antagonist, W-7. 6. Thus
      furosemide elicits a rise in Ca2+i which, via calmodulin, results in activation
      of Na(+)-H+ exchange. The resulting intracellular alkalinization would be
      expected to increase channel activity.

PMID- 9023768
TI  - Regulation of intracellular pH in salamander retinal rods.
AB  - 1. We measured intracellular pH (pHi) in rods isolated from the retina of the
      axolotl salamander, Ambystoma mexicanum, using the fluorescent indicator 2',7'
      bis(carboxyethyl)-5(and -6)-carboxyfluorescein (BCECF). 2. The light exposures
      associated with data acquisition had no marked effect on pHi. There was no sharp
      change between the value obtained from the first exposure of dark-adapted rods
      and subsequent readings. Increasing the acquisition frequency from 1 to 10 min-1
      either had no effect, or brought about a slow acidification, which was stopped or
      reversed when the low frequency was restored. 3. In nominally HCO3(-)-free
      solution at pH 7.5, the rods had a steady-state pHi of 7.09 +/- 0.02 (n = 46) and
      a buffering power (beta i) of 24 +/- 1 mM (pH unit)-1 (n = 48). The buffering
      power was virtually constant in the pH range 6.6-8.0. In the same range, pHi
      dependent linearly on perfusion pH (pHo) with regression coefficients of 0.4-0.5.
      4. There were no significant differences between the inner and outer segment of
      intact rods as regards steady-state pHi or responses to experimental treatments.
      5. Recovery from an intracellular acid load imposed by sodium propionate or an
      NH4Cl prepulse in nominally bicarbonate-free perfusate was completely blocked by
      decreasing the extracellular Na+ concentration to 7 mM, and slowed by 86% by
      applying 1 mM amiloride. 6. Introduction of 2% CO2-13 mM HCO3- caused an
      alkalinization that was often preceded by a transient acidification. Steady-state
      pHi was on average 0.1 pH units higher than in nominally bicarbonate-free
      solution. The mean acid extrusion rate, calculated on the assumption that CO2
      HCO3- behaves as an open system, was 19% higher (31 +/- 2 mM h-1) than in a
      solution buffered only by Hepes (26 +/- 2 mM h-1). 7. In the presence of CO2-HCO3
      , 100 microM 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) decreased
      the acid extrusion rate by 20% on average. Lowering the extracellular Cl
      concentration to 7 mM raised pHi, but did not significantly affect the acid
      extrusion rate. 8. We conclude that retinal rods regulate pHi by both Na(+)-H+
      exchange and mechanism(s) involving HCO3(-)-Cl- exchange. In the present
      conditions, the Na(+)-H+ exchanger appears as the dominant mechanism for acid
      extrusion.

PMID- 9023769
TI  - Potassium currents in acutely isolated human hippocampal dentate granule cells.
AB  - 1. Properties of voltage- and Ca(2+)-dependent K+ currents were investigated in
      thirty-four dentate granule cells acutely isolated from the resected hippocampus
      of eleven patients with therapy-refractory temporal lobe epilepsy (TLE). 2. When
      intracellular Ca2+ was strongly buffered with 11.5 mM EGTA-1 mM Ca2+ in the
      recording pipette, K+ currents (IK) with a slow activation and biexponential time
      dependent decay could be elicited, which showed a threshold for activation around
      -30 mV. 3. A contribution of Ca(2+)-dependent K+ currents became apparent with
      intracellular solution containing 1 mM BAPTA-0.1 mM Ca2+. Superfusion of low-Ca2+
      extracellular solution blocked 43% of outward currents in this recording
      configuration. Outward current components could also be blocked by substituting 5
      mM Ba2+ for extracellular Ca2+ (78%), or by application of 100 microM Cd2+ (25%).
      4. The Ca(2+)-dependent K+ currents could be pharmacologically subdivided into
      two components. One component was sensitive to 500 microM tetraethylammmonium
      (TEA; 41%) and 10 nM charybdotoxin (CTX; 47.2%). The blocking effects of 10 nM
      CTX and 500 microM TEA were not additive, suggesting that both agents block the
      same conductance. A second, smaller outward current component was blocked by 50
      nM apamin (13%). 5. A transient A-type K+ current could be observed in six
      neurones and showed a fast monoexponential time-dependent inactivation with a
      steady-state voltage dependence that was distinct from that of IK. The A-type
      current was blocked by 4-aminopyridine (4-AP) but not by TEA or low-Ca2+
      solution. 6. We conclude that outward currents in human hippocampal dentate
      granule cells can be separated into at least four types by their kinetic and
      pharmacological properties. These include at least one voltage-dependent current
      similar to those observed in mammalian hippocampal neurones, and two Ca(2+)
      dependent K+ currents that most probably correspond to SK- and BK-type currents.
      A classical A-type current could be detected in some patients with Ammon's horn
      sclerosis (AHS) but not in patients with lesion-associated TLE.

PMID- 9023770
TI  - Properties of cloned ATP-sensitive K+ currents expressed in Xenopus oocytes.
AB  - 1. We have studied the electrophysiological properties of cloned ATP-sensitive K+
      channels (KATP channels) heterologously expressed in Xenopus oocytes. This
      channel comprises a sulphonylurea receptor subunit (SUR) and an inwardly
      rectifying K+ channel subunit (Kir). 2. Oocytes injected with SUR1 and either
      Kir6.2 or Kir6.1 exhibited large inwardly rectifying K+ currents when cytosolic
      ATP levels were lowered by the metabolic inhibitors azide or FCCP. No currents
      were observed in response to azide in oocytes injected with Kir6.2, Kir6.1 or
      SUR1 alone, indicating that both the sulphonylurea receptor (SUR1) and an inward
      rectifier (Kir6.1 or Kir6.2) are needed for functional channel activity. 3. The
      pharmacological properties of Kir6.2-SUR1 currents resembled those of native beta
      cell ATP-sensitive K+ channel currents (KATP currents): the currents were > 90%
      blocked by tolbutamide (500 microM), meglitinide (10 microM) or glibenclamide
      (100 nM), and activated 1.8-fold by diazoxide (340 microM), 1.4-fold by pinacidil
      (1 mM) and unaffected by cromakalim (0.5 mM). 4. Macroscopic Kir6.2-SUR1 currents
      in inside-out patches were inhibited by ATP with a Ki of 28 microM. Kir6.1-SUR1
      currents ran down within seconds of patch excision preventing analysis of ATP
      sensitivity. 5. No sensitivity to tolbutamide or metabolic inhibition was
      observed when SUR1 was coexpressed with either Kir1.1a or Kir2.1, suggesting that
      these proteins do not couple in Xenopus ocytes. 6. Our data demonstrate that the
      Xenopus oocyte constitutes a good expression system for cloned KATP channels and
      that expression may be assayed by azide-induced metabolic inhibition.

PMID- 9023772
TI  - Solvent-dependent rate-limiting steps in the conformational change of sodium
      channel gating in squid giant axon.
AB  - 1. The time course of sodium currents (INa) in squid giant axon was analysed
      using viscous non-electrolyte solutions on both sides of the axolemma. It slowed
      reversibly as the non-electrolyte concentration increased. The activation,
      deactivation (closing) and inactivation processes were slowed in a similar
      manner. The gating current of the sodium channel was also slowed to the same
      extent as the activation time constant. 2. The voltage dependence observed in a
      time constant vs. voltage relationship and a chord conductance vs. voltage
      relationship (activation curve), did not change significantly. 3. The gating
      kinetics have a similar temperature dependence in non-electrolyte solutions,
      showing that the basic gating mechanism did not change in these solutions and
      only a slight increase in the activation free energy was one of the main causes
      of slowing. 4. Eight non-electrolytes, formamide, ethylene glycol, glycerol,
      erythritol, glucose, sorbitol, sucrose and polyethylene glycol (mean molecular
      weight 600) were used. The amount of slowing was correlated with the gram
      concentration (g l-1) of non-electrolytes, but not with molar concentration (M)
      and solution osmolarity (osmol l-1). 5. The percentage changes of the time
      constant were expressed as a function of the relative change in solution
      viscosity, eta/eta0. The proportionality constants alpha in the relationship
      alpha (eta/eta0), and gamma in the relationship 100 (eta/eta0)gamma, obtained
      using different non-electrolytes, were close to 100% and 1, respectively. The
      simplest model to explain the results assumes that a slowing of a global
      conformational change is a consequence of sequential viscosity-dependent
      movements of local structures (viscosity model). 6. Values of alpha and gamma
      deviated frequently from those in an ideal case, i.e. 100% for alpha and 1 for
      gamma, and they scattered, having a tendency to decrease as a function of
      molecular weight. 7. The slowing was also expressed as an exponential function of
      the solution osmolarity. A predicted solute-inaccessible volume Va ranged (in nm3
      per molecule) between 0.09 and 1.45. The value of Va increased as a logarithmic
      function of the molecular weight of the non-electrolyte. 8. This solute
      inaccessible volume should be distributed in all hydrophilic parts of the sodium
      channel protein, but is not located in the channel conducting pore itself. The
      slowing of gating could be explained by a model in which a rate-limiting step is
      a hydration process that occurs after local small structural changes have exposed
      new, unhydrated faces (transient hydrated-states model). 9. Considering the
      opposite dependencies of parameters alpha (or gamma) and beta on the molecular
      weight, sodium channel gating is likely to reflect a combination of these two
      models, which are coupled in microscopic segment movements. We emphasize with
      this combination of models that fluctuating hydrophilic structures play an
      important role in determining time constants in the gating process.

PMID- 9023771
TI  - Modulation of Na+,K(+)-ATPase activity by a tyrosine phosphorylation process in
      rat proximal convoluted tubule.
AB  - 1. In the rat kidney proximal convoluted tubule, epidermal growth factor and
      insulin have been reported to stimulate Na+ reabsorption. Because most of the
      effects of these growth factors are mediated by a process of tyrosine
      phosphorylation and Na+,K(+)-ATPase drives Na+ reabsorption, the influence of
      tyrosine kinases and tyrosine phosphatases on Na+,K(+)-ATPase activity located in
      the proximal convoluted tubule was evaluated. 2. Activation of receptor tyrosine
      kinases by epidermal growth factor and insulin stimulated ouabain-sensitive 86Rb+
      uptake. The effects of epidermal growth factor and insulin were prevented by
      genistein, a tyrosine kinase inhibitor, but were unaffected by GF109203X, a
      protein kinase C inhibitor. 3. Inhibition of tyrosine phosphatases by
      orthovanadate (10(-7) and 10(-6)M) mimicked the effects of activation of receptor
      tyrosine kinases: stimulation of the ouabain-sensitive 86Rb+ uptake and of the
      hydrolytic activity of Na+,K(+)-ATPase under rate-limiting Na+ concentration, and
      absence of modification of the maximal activity (Vmax) of the enzyme. The effects
      of orthovanadate and insulin on the ouabain-sensitive 86Rb+ uptake were not
      additive. 4. The present results show that both activation of receptor tyrosine
      kinases and inhibition of tyrosine phosphatases stimulate the Na+,K(+)-ATPase
      activity through a common mechanism. Thus, a tyrosine phosphorylation process
      directly controls the Na+,K(+)-ATPase activity and contributes to the
      physiological control of water and solute reabsorption in the proximal convoluted
      tubule.

PMID- 9023773
TI  - Channel modulation by tyrosine phosphorylation in an identified leech neuron.
AB  - 1. We have examined the effects of tyrosine phosphorylation on a spontaneously
      active cation channel that also participates in the modulation of pressure
      sensitive (P) neurons in the leech. Cation channel activity in cell-attached or
      isolated, inside-out membrane patches from P cells in culture was monitored
      before and after treatments that altered the level of tyrosine phosphorylation.
      2. In cell-attached recordings from intact P cells, bath application of
      genistein, an inhibitor of tyrosine kinases, resulted in a 6.6 +/- 2.6-fold
      increase in channel activity with no change in the mean open time or amplitude.
      Daidzein, an inactive form of genistein, was without effect. Addition of
      pervanadate, a membrane-permeant inhibitor of tyrosine phosphatases, had no
      effect on its own and blocked the effect of subsequent addition of genistein. 3.
      In inside-out P cell membrane patch recordings, exposure to a catalytically
      active fragment of a tyrosine phosphatase resulted in a 10.3 +/- 3.6-fold
      increase in channel activity with no change in the mean open time or amplitude.
      Orthovanadate had no effect on channel activity and, when added with the
      phosphatase, prevented the increase in activity. 4. Our results demonstrate that
      the basal activity of cation channels is increased by tyrosine dephosphorylation,
      suggesting a constitutive modulation of channel activity under resting
      conditions.

PMID- 9023774
TI  - Purinoceptor-operated cationic channels in human B lymphocytes.
AB  - 1. Using the patch clamp method in the outside-out configuration, purinoceptor
      dependent unitary currents were measured in tonsillar and transformed tonsillar
      human B lymphocytes. 2. Single channel currents were evoked by ATP4-, the free
      acid form of ATP, and by 2',3' O-benzoyl-4-benzoyl-ATP (BzATP) in the micromolar
      concentration range, but not by 10 mM ADP3- or 0.5 mM Mg(2+)-bound ATP. 3. The
      channels could be activated and deactivated several times for as long as 30 min
      even in the absence of intracellular ATP, GTP, or glucose. 4. The channels were
      selective for small cations and had a conductance of 9 pS with Cs+ as the
      intracellular and Na+ as the extracellular monovalent cation. 5. The half-maximal
      activation of the channels was obtained by 114 microM ATP4- and by 16 microM
      BzATP. The increase in the open probability after raising the ATP4- concentration
      was mainly due to a decrease in the times the channels spend in the closed state.
      6. It is concluded that human B lymphocytes possess cationic channels directly
      gated by extracellular ATP4-. Their agonist binding characteristics are typical
      for P2z purinoceptors, but their permeation behaviour is different from the large
      non-specific pores formed by ATP4- in fibroblasts, macrophages and mast cells.

PMID- 9023775
TI  - Brain-derived neurotrophic factor and nerve growth factor potentiate excitatory
      synaptic transmission in the rat visual cortex.
AB  - 1. The effect of brain-derived neurotrophic factor (BDNF) and nerve growth factor
      (NGF) on excitatory synaptic transmission in the developing visual cortex was
      studied by whole-cell patch-clamp recordings from rat brain slices. 2. Both
      neurotrophins induced a rapid increase in the amplitude of impulse-evoked
      excitatory postsynaptic currents (EPSCs). BDNF also increased the frequency of
      spontaneous EPSCs. 3. Analysis of the currents revealed that alpha-amino-3
      hydroxy-5-methyl-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA)
      receptor-mediated components contributing to the EPSC peak amplitude were equally
      potentiated by the neurotrophins. 4. When synaptic transmission was studied by
      minimal stimulation of intracortical afferents, neurotrophins induced a decrease
      in the occurrence of release failures. 5. A number of neurones were insensitive
      to the effects of the neurotrophins, possibly related to the considerable
      heterogeneity of neuronal types and to the uneven distribution of neurotrophin
      receptors in the visual cortex. 6. The probability of neurotransmitter release
      represents a rapidly modifiable synaptic feature by which neurotrophins can
      potentiate the efficacy of excitatory synaptic transmission in the visual cortex.

PMID- 9023776
TI  - Protein kinase A-mediated enhancement of miniature IPSC frequency by
      noradrenaline in rat cerebellar stellate cells.
AB  - 1. Cellular mechanisms underlying the enhancement by noradrenaline (NA) of
      inhibitory postsynaptic currents (IPSCs) were studied at inhibitory synapses in
      the molecular layer of the cerebellum. IPSCs were obtained from stellate cells in
      rat cerebellar slices using tight-seal whole-cell recording. 2. Miniature IPSCs
      (mIPSCs) were recorded in the presence of tetrodotoxin (TTX; 100 nM). NA (10
      microM) markedly increased the frequency of mIPSCs, but did not alter their mean
      amplitude. Bath application of the inhibitor of adenylyl cyclase 9-(tetrahydro-2'
      furyl) adenine (SQ 22,536; 300 microM), of the wide spectrum protein kinase
      inhibitor staurosporine (1 microM), and of the Rp-diastereomer of adenosine-3',5'
      cyclic monophosphothioate (Rp-cAMPS; 500 microM), a specific inhibitor of cAMP
      dependent protein kinase (PKA), inhibited the mIPSC frequency increase induced by
      NA. 3. The increase in mIPSC frequency was not attenuated by Cd2+ (100 microM), a
      blocker of voltage dependent calcium channels. However, after a 12-15 min pre
      incubation in Ca(2+)-free saline, the effect of NA on mIPSCs was markedly
      inhibited. If Ca2+ ions were readmitted in the presence of NA, enhancement of the
      mIPSC frequency was largely restored. 4. Application of the membrane permeant
      analogue of cAMP, 8-Br-cAMP (1 mM), together with the inhibitor of cAMP
      phosphodiesterase, 3-isobutyl-1-methylxanthine (IBMX; 100 microM), caused a
      frequency increase of mIPSCs. Forskolin also mimicked the stimulatory effect of
      NA on mIPSC frequency. The effects of both 8-Br-cAMP and forskolin persisted in
      Ca(2+)-free saline, suggesting that the modulation of transmitter release does
      not require Ca2+ influx. 5. On the whole, the results indicate that the
      potentiation of mIPSC frequency by NA is mediated through the sequential
      activation of adenylyl cyclase and protein kinase A (PKA), and that PKA modulates
      the vesicle release mechanism rather than Ca2+ influx. The lack of effect of NA
      after prolonged incubation in Ca(2+)-free solution may be due to an inhibition of
      adenylyl cyclase by a gradual lowering of the cytosolic presynaptic Ca2+
      concentration.

PMID- 9023777
TI  - Pacemaker activity in a sensory ending with multiple encoding sites: the cat
      muscle spindle primary ending.
AB  - 1. A combined physiological, histological and computer modelling study was
      carried out on muscle spindles of the cat tenuissimus muscle to examine whether
      there was any correlation between the functional interaction of putative encoding
      sites, operated separately by static and dynamic fusimotor neurones, and the
      topological structure of the preterminal branches of the primary sensory ending.
      2. Spindles, whose I a responses to stretch and separate and combined static and
      dynamic fusimotor stimulation were recorded in physiological experiments, were
      located in situ. Subsequently the ramifications of the sensory ending were
      reconstructed histologically, and the topology of the branch tree was used in
      computer simulations of I a responses to examine the effect of the electronic
      separation of encoding sites on the static-dynamic interaction pattern. 3.
      Interactions between separate static and dynamic inputs, manifest in responses to
      combineed stimulation, were quantified by a coefficient of interaction (Ci)
      which, by definition, was 1 for strictly linear summation of separate inputs and
      zero for maximum occlusion between inputs. 4. For the majority of spindles static
      dynamic interactions were characterized by pronounced occlusion (C1 < 0.35). In
      these spindles putative encoding sites (the peripheral heminodes of the branches
      supplying the intrafusal fibres activated by individual fusimotor efferents) were
      separated by a minimum conduction path of between three and ten myelinated
      segments (2-9 nodes of Ranvier). In contrast, significant summation (C1,
      approximately 0.7) was found in only one spindle. In this case putative encoding
      sites were separated by a single node. 5. Occlusion was not due to encoder
      saturation and it could not be accounted for by any other known physiological
      mechanisms (intrafusal fatigue or unloading). It is therefore attributed to
      competitive pacemaker interaction between encoding sites which are largely
      selectively operated by static and dynamic fusimotor efferents. 6. Model
      simulations of real preterminal-branch tree structures confirmed that short
      conduction paths between encoding sites were associated with manifest summation,
      whereas longer minimum conduction paths favoured pronounced occlusion. 7. In the
      extreme, occlusion could be so pronounced as to give rise to negative values of
      C1 during critical segments of response cycles. This was associated with lower
      discharge rates during combined static and dynamic stimulation than the higher of
      the individual stimulation effects. This phenomenon is referred to as
      hyperocclusion. Computer simulations demonstrated that hyperocclusion could be
      accounted for by a slow ionic adaptation process. e.g. by a very slowly
      activating K+ conductance.

PMID- 9023778
TI  - Role of ganglionic cotransmission in sympathetic control of the isolated bullfrog
      aorta.
AB  - 1. The relation between preganglionic activity and arterial tone was studied in
      preparations of bullfrog lumbar sympathetic ganglia 7-10 and the dorsal aorta. 2.
      Two or more stimuli evoked contractions when applied to the preganglionic C, but
      not the B pathway. Contractions were blocked when transmission in ganglia 9 and
      10 was disrupted by cutting the sympathetic chain or adding (+)-tubocurarine.
      Contractions were antagonized by postganglionic action of guanethidine, but not
      by phentolamine or suramin. 3. Aortic responses to short trains (10-100 stimuli)
      were half-maximal at 0.3-0.5 Hz, saturated near 1 Hz and had a minimum latency of
      8.9 s. By contrast, responses to 300 stimuli were half-maximal at 1 Hz and became
      2.5-fold larger at 10 Hz. 4. Exogenous luteinizing hormone releasing hormone
      (LHRH) potentiated preganglionically evoked contractions. Endogenous LHRH
      mediated contractions evoked by 10 Hz stimulation in (+)-tubocurarine. These
      responses had a longer latency than in normal Ringer solution and were blocked by
      [D-pGlu1, D-Phe2, D-Trp3.6]-LHRH. The LHRH antagonist did not alter contractions
      evoked by continuous stimulation in normal Ringer solution or by bursts of
      stimuli in hexamethonium. 5. Exogenous neuropeptide Y (NPY) potentiated
      neurogenic contractions and responses to adrenaline. Benextramine blocked
      contractions produced by nerve stimulation, adrenaline and NPY, but not ATP. 6.
      The results show that contractions of the isolated aorta are tuned to
      physiological frequencies of activity in sympathetic C neurones. Peptidergic
      cotransmission in the ganglia can increase arterial tension, but not during
      synchronous activation of primary nicotinic synapses. It is suggested that the
      physiological role of LHRH arises from interactions with subthreshold nicotinic
      EPSPs and that postganglionic release of NPY shifts frequency tuning of the
      circuit during prolonged activity.

PMID- 9023779
TI  - Intestinal blood flow is controlled by both feed arteries and microcirculatory
      resistance vessels in freely moving rats.
AB  - 1. In freely moving rats, intestinal blood flow, aortic blood pressure and blood
      pressure at the base of mesenteric arcades were measured simultaneously so as to
      determine the role of feed arteries and of the microcirculation in the control of
      intestinal vascular resistance. Segmental resistances of feed arteries (Rfeed)
      and of microcirculatory vessels (Rmicro) were calculated. 2. At rest, Rfeed and
      Rmicro were 32 and 68%, respectively, of the total intestinal vascular
      resistance. 3. Injection of noradrenaline (2 micrograms i.v,) increased Rfeed by
      151% and Rmicro by 243%. Angiotensin II (400 ng i.v.) did not increase Rfeed
      significantly, but increased Rmicro by 239%. Conversely, serotonin (15 micrograms
      i.v.) increased Rfeed by 414% but did not affect Rmicro significantly. 4.
      Spontaneous physical activity increased Rfeed by 29% and Rmicro by 39%, while
      sudden environmental stress increased Rfeed by 116% and Rmicro by 129%. Infused
      noradrenaline (1 microgram min-1 i.v.) or adrenaline (0.8 microgram min-1 i.v.)
      reduced intestinal flow by 21 and 16% respectively, while noradrenaline, but not
      adrenaline, increased intestinal resistances. 5. alpha 1-Blockade with prazosin
      (0.1 mg i.v.) reduced Rfeed and Rmicro by 43 and 16%, respectively. Thereafter,
      environmental stress decreased Rfeed by 24% while Rmicro was unaffected.
      Intravenous noradrenaline and adrenaline responses were attenuated. 6. We
      conclude that in freely moving rats, mesenteric feed arteries, as well as
      microcirculatory vessels, are true resistance vessels, and that both participate
      in the control of intestinal blood flow.

PMID- 9023780
TI  - The shape of indicator dilution curves used for cardiac output measurement in
      man.
AB  - 1. In six patients arterial plasma lithium concentration-time curves were
      recorded following injection of lithium chloride into the right or left atrium.
      2. Lognormal curve fitting was used to derive the areas under the first pass
      dilution curves. 3. Subjecting the curves produced by left atrial injection to a
      delay and sequential filtering produced curves that closely approximated those
      produced by right atrial injection. 4. We conclude that the transfer function of
      the right heart and lungs is equivalent to a delay and sequential filtering, that
      the primary indicator dilution curve is closely approximated by a lognormal curve
      and that loss of lithium in the lungs following right atrial injection is
      clinically insignificant.

PMID- 9023781
TI  - The decrease of maximal oxygen consumption during hypoxia in man: a mirror image
      of the oxygen equilibrium curve.
AB  - 1. Endurance athletes (E) undergo a marked reduction of arterial O2 saturation
      (Sa,O2) at maximal exercise in normoxia, which disappears when they breathe
      hyperoxic mixtures. In addition, at a given level of hypoxia, the drop in maximal
      O2 consumption (VO2,max) is positively related to the individual normoxic
      VO2,max. 2. These data suggest that the curve relating VO2,max to PI,O2 may be
      steeper and perhaps less curved in E than in sedentary subjects (S) with low
      VO2,max values because of the greater hypoxaemia in the latter, whence the
      hypotheses that (i) the relationship between VO2,max and PI,O2 may be set by the
      shape of the oxygen equilibrium curve; and (ii) the differences between E and S
      may be due to the different position on the oxygen equilibrium curve on which
      these subjects operate. These hypotheses have been tested by performing a
      systematic comparison of the VO2,max or Sa,O2 vs. PI,O2 relationships in E and S.
      3. On ten subjects (five S and five E), VO2,max was measured by standard
      procedure during cycloergometric exercise. Sa,O2 was measured by finger-tip
      infrared oximetry. Arterialized blood PO2 (Pa,O2) and PCO2 (Pa,CO2) were
      determined in 80 microliters blood samples from an ear lobe. The subjects
      breathed ambient air or a N2-O2 mixture with an inspired O2 fraction (FI,O2) of
      0.30, 0.18, 0.16, 0.13 and 0.11, respectively, VO2,max was normalized with
      respect to that obtained at the highest FI,O2. 4. The relationships between Sa,O2
      or normalized VO2,max and FI,O2 (or PI,O2) had similar shapes, the data for E
      being systematically below and significantly different from those for S. Linear
      relationships between Sa,O2 and normalized VO2,max, statistically equal between E
      and S, were found. 5. We conclude that the relationships between either VO2,max
      or Sa,O2 and FI,O2 (or Pa,O2) may indeed be the mirror images of one another,
      implying a strict link between the decrease of VO2,max in hypoxia and the shape
      of the oxygen equilibrium curve, as hypothesized.

PMID- 9023782
TI  - Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in
      inflammation.
AB  - 1. The present study tested the hypothesis that the level of xanthine oxidase is
      elevated in injured human skeletal muscle in association with inflammatory
      events. Seven male subjects performed five bouts of strenuous one-legged
      eccentric exercise. Muscle biopsies from both the exercised and the control leg,
      together with venous blood samples, were obtained prior to exercise and at 45
      min, 24, 48 and 96 h after exercise. The time courses of xanthine oxidase
      immunoreactivity and indicators of muscle damage and inflammation were examined.
      2. The number of xanthine oxidase structures observed by immunohistological
      methods in the exercised muscle was up to eightfold higher than control from day
      1 to day 4 after exercise (P < 0.05). The increase was attributed to an enhanced
      expression of xanthine oxidase in microvascular endothelial cells and an invasion
      of leucocytes containing xanthine oxidase. 3. The concentration of plasma
      interleukin-6 was significantly higher 90 min after exercise than before exercise
      (P < 0.05) and remained higher than pre-exercise levels throughout the 4 days. On
      day 4 the plasma creatine kinase activity was approximately 150-fold higher (P <
      0.05) than resting levels. 4. Despite the increase in xanthine oxidase in the
      muscle there were no detectable changes in the levels of muscle malondialdehyde
      or in plasma antioxidant capacity up to 4 days post-exercise. 5. It is concluded
      that eccentric exercise leads to an increased level of xanthine oxidase in human
      muscle and that the increase is associated with secondary inflammatory processes.
      The increase in xanthine oxidase in the muscle occurs mainly in microvascular
      endothelial cells, but occurs also via infiltrating leucocytes containing
      xanthine oxidase. A role for leucocytes in xanthine oxidase induction in
      endothelium is proposed.

PMID- 9023783
TI  - Spindle and motoneuronal contributions to the phase advance of the human stretch
      reflex and the reduction of tremor.
AB  - 1. The human stretch reflex is known to produce a phase advance in the EMG
      reflexly evoked by sinusoidal stretching, after allowing for the phase lag
      introduced by simple conduction. Such phase advance counteracts the tendency to
      tremor introduced by the combined effect of the conduction delay and the slowness
      of muscle contraction. The present experiments confirm that the EMG advance
      cannot be attributed solely to the phase advance introduced by the muscle
      spindles, and show that a major additional contribution is provided by the
      dynamic properties of individual motoneurones. 2. The surface EMG was recorded
      from biceps brachii when two different types of sinusoidally varying mechanical
      stimuli were applied to its tendon at 2-40 Hz. The first was conventional
      sinusoidal displacement ('stretch'); the spindle discharge would then have been
      phase advanced. The second was a series of weak taps at 103 Hz, with their
      amplitude modulated sinusoidally ('modulated vibration'). The overall spindle
      discharge should then have been in phase with the modulating signal, since the
      probability of any individual 1 a fibre responding to a tap would increase with
      its amplitude. The findings with this new stimulus apply to motoneurone
      excitation by any rhythmic input, whether generated centrally or peripherally. 3.
      The sinusoidal variation of the EMG elicited by the modulated vibration still
      showed a delay-adjusted phase advance, but the value was less than that for
      simple stretching. At 10 Hz the difference was 70-80 deg. This was taken to be
      the phase advance introduced by the spindles, very slightly underestimated
      because of the lags produced by tendon compliance in transmitting sinusoidal
      stretch to the muscle proper. The adjusted phase advance with modulated vibration
      was taken to represent that introduced by the reflex centres, undistorted by
      tendon compliance. At 10 Hz the reflex centres produced about the same amount of
      phase advance as the muscle spindles. 4. At modulation frequencies above 10 Hz
      the adjusted central phase advance remained approximately constant. However, when
      the frequency was reduced to below 6 Hz the central phase advance decreased. The
      depth of EMG modulation (reflex gain) also fell rapidly, starting from a slightly
      higher frequency. Thus the central phase advance mechanisms behave like a high
      pass filter. 5. A simple model of the motoneurone, incorporating synaptic noise
      and an after-hyperpolarization, was tested with sinusoidal inputs and gave a
      phase advance over a wide range of frequencies. The effect was tightly linked to
      two particular facets of the motor discharge; these were the ratio between the
      stimulus frequency and the mean firing rate (the 'carrier frequency' of the
      unit), and the coefficient of variation of the interspike interval distribution.
      The gain rose to a maximum at the carrier frequency, while the phase advance
      showed a maximum at 0.8 of the carrier. The more regular the discharge, the
      greater were these effects. The phase advance might increase to above 90 deg,
      showing that the motoneurone potentially provides a major contribution to the
      phase advance of the stretch reflex. Related effects have already been observed
      in other neuronal models and for the discharge of the muscle spindle, without
      their significance for the motoneurone being appreciated. In essence, a
      rhythmically firing neurone is particularly affected by a rhythmic stimulus when
      the two frequencies approximately coincide. 6. Recording from single human motor
      units confirmed the role of the 'carrier frequency' in determining the phase
      advance with sinusoidal inputs. In particular, for both stretching and modulated
      vibration, the phase advance of the response elicited by a fixed sinusoidal
      stimulus changed appropriately when the firing rate of the unit varied
      'spontaneously' over a long recording period. 7. Thus a combination of modelling
      and experiment has shown that the motoneurones themselves produce a significant
      phase advance.

PMID- 9023784
TI  - Latent addition in motor and sensory fibres of human peripheral nerve.
AB  - 1. The time constants of motor and sensory nerve fibres were studied in normal
      human ulnar nerves by the method of latent addition, using threshold tracking to
      follow the recovery of excitability after brief conditioning current pulses. The
      60 microseconds test and conditioning stimuli were applied at the wrist, and the
      conditioning stimuli were set to 90, 60, 30, -30, -60 and -90% of the control
      threshold current. Compound muscle action potentials were recorded from abductor
      digiti minimi, and sensory nerve action potentials from the little finger. 2.
      Recovery from depolarizing conditioning pulses was slower than recovery from
      hyperpolarizing pulses and strongly dependent on conditioning pulse amplitude.
      The voltage dependence of latent addition was attributed to subthreshold
      activation of sodium channels (local response). 3. Motor and sensory nerve
      excitability generally recovered from -90% hyperpolarizing pulses as the sum of
      two exponential components, although the slow component was negligible in some
      motor nerves. The fast component (time constant 43.3 +/- 2.0 microseconds, mean
      +/- S.E.M., n = 9) was similar between motor and sensory fibres in the same
      subject. It showed no consistent voltage dependence, and was attributed to a
      passive input time constant of the fibres. The slow component of recovery from
      hyperpolarizing pulses was greater in sensory than in motor fibres and was
      voltage dependent: it could be greatly increased in motor and sensory fibres by
      steady depolarization. It was attributed to a regenerative membrane current,
      active at the resting potential in sensory and at least some motor nerves. 4. The
      latent addition responses were compared with the computed responses of four
      theoretical models. Both motor and sensory responses were well fitted by a model
      in which a fraction of the sodium channels (less in motor than in sensory fibres)
      were activated at potentials 20 mV more negative than normal and at half the
      normal rate, and did not inactivate. 5. It is concluded that the differences in
      latent addition between motor and sensory fibres are primarily due to differences
      in non-classical, voltage-dependent ion channels, active close to the resting
      potential. These "threshold channels' may help to account for the longer strength
      duration time constant of sensory fibres, for their lower rheobase, and for their
      greater tendency to fire repetitively.

PMID- 9023785
TI  - The electroencephalographic sleep pattern in schizophrenic patients treated with
      clozapine or classical antipsychotic drugs.
AB  - The effects of antipsychotic agents on sleep were tested by examining the
      nocturnal electroencephalographic recordings of 14 drug-naive schizophrenic
      patients and comparing these with recordings from 12 patients treated with
      clozapine and 10 treated with classical neuroleptics (haloperidol: n = 7;
      flupentixol: n = 3). In both of the treated groups, sleep continuity measures and
      rapid eye movement (REM) density were significantly higher than in the drug-naive
      group. Clozapine-treated patients showed significantly more stage two sleep, more
      stable non-REM sleep (stages two, three and four) and less stage one than
      patients treated with haloperidol or flupentixol. Clozapine had no effect on the
      amount of REM sleep. Although mean REM latency was almost twice as long in the
      clozapine compared with the other two groups, this difference was not
      statistically significant. The present study suggests considerable differences
      between the influence of typical and atypical antipsychotic agents on sleep.
      However, the results of this cross-sectional study should be confirmed using a
      longitudinal intraindividual approach.

PMID- 9023786
TI  - Cultured skin fibroblasts as a cell model for investigating schizophrenia.
AB  - Cultured skin fibroblasts, among other non-neuronal cells (e.g. platelets,
      lymphocytes, red blood cells), provide an advantageous system for investigating
      dynamic molecular regulatory processes underlying abnormal cell growth,
      metabolism, and receptor-mediated signal transduction, without the confounding
      effects of disease state and its treatment in a variety of brain disorders,
      including schizophrenia, and are useful for studies of systemic biochemical
      defects with predominant consequences for brain function. These cells are also
      useful for studying aspects of neurotransmitter functions because the cells
      express enzymes involved in their metabolism, as well as their receptors with
      complete machinery for signal transduction. These processes also function
      predictably with receptors that are transfected in fibroblasts. This review will
      focus on the use of cultured skin of which have also been studied in post-mortem
      brains. These mechanisms might involve DNA processing and mitogenesis, cell-cell
      adhesion molecules, actions of growth factors, oxidative damage, and membrane
      phospholipid derived second messengers. This review will further discuss the
      implications of these processes to clinical and structural brain abnormalities.
      An understanding of these biochemical processes might help establish therapeutic
      implications and identify the risk for illness through experimental strategies
      such as epidemiology, family pedigree and high risk populations. Finally, despite
      some methodological limitations, skin fibroblasts are relatively easy to grow and
      maintain as primary cultures or as immortalized cell lines for long periods of
      time for use in investigating newly identified biochemical abnormalities.

PMID- 9023787
TI  - A randomized, double-blind comparison of a rapidly escalating dose of venlafaxine
      and imipramine in inpatients with major depression and melancholia.
AB  - A double-blind, randomized, parallel study in 167 hospitalized patients with
      major depression and melancholia was conducted to determine if rapidly escalated
      doses of venlafaxine produced an earlier response, compared with rapidly
      escalated doses of imipramine. The daily dose of venlafaxine was rapidly
      increased to 375 mg/day over a five-day period, was maintained at this level for
      10 days, and then was reduced to 150 mg/day for the remainder of the study. The
      imipramine dose was rapidly increased to 200 mg/day over five days and was
      maintained at this level to the end of the study. The primary efficacy variables
      were time to response and time to sustained response on the HAM-D and MADRS. No
      differences in the response rates on the HAM-D or MADRS were observed between
      treatments. However, among patients who demonstrated a response on the HAM-D,
      there was a significantly faster onset of response (p = 0.036) and sustained
      response (p = 0.018) in the venlafaxine group. The median time to response on the
      HAM-D among responders was 14 days with venlafaxine and 21 days with imipramine.
      However, no differences between treatments were observed among responders on the
      MADRS (median time to response: 15 days for venlafaxine, 18 days for imipramine).
      Study events were reported in 69% of venlafaxine-treated patients and 76% of
      imipramine-treated patients. In severely depressed patients with melancholia, a
      faster onset of response was observed with venlafaxine on the HAM-D, but not the
      MADRS, and maximal tolerated doses of venlafaxine and imipramine were comparable
      for overall efficacy. These results confirm and extend previous observations and
      suggest that venlafaxine may have an early onset of action and may produce a
      rapid response in hospitalized patients with severe depression complicated by
      melancholia.

PMID- 9023788
TI  - Moclobemide versus fluoxetine for double depression: a randomized double-blind
      study.
AB  - The efficacy and tolerability of the selective reversible monoamine oxidase A
      inhibitor, moclobemide (300 mg/day) and the selective serotonin uptake inhibitor,
      fluoxetine (200 mg/day), were compared in a six-week single-centre double-blind
      fixed-dose study in patients (n = 42) with double depression (DSM-III-R:
      dysthymia with superimposed major depressive episode) using weekly assessment on
      the Hamilton depression rating scale (HDRS-17 items) and clinical global
      impression (CGI) scale. The primary efficacy outcome measure was a decrease > or
      = 50% in end of treatment HDRS score, secondary measures were the mean total
      endpoint HDRS scores and percentages of CGI very good and good responses.
      Tolerability was measured by the frequency and severity of volunteered adverse
      events. There were no significant differences in secondary efficacy outcome
      measures, but more patients achieved a > or = 50% decrease in HDRS score on
      moclobemide (71% vs 38%, p < 0.05). The only adverse event was mild transient
      anxiety (n = 1) with moclobemide. The results suggest that moclobemide and
      fluoxetine are equally well tolerated and at least similar in efficacy in double
      depression. Evidence that moclobemide may be more effective requires confirmation
      in a larger comparative study incorporating a placebo control group.

PMID- 9023789
TI  - Hostility changes following antidepressant treatment: relationship to stress and
      negative thinking.
AB  - It is unclear whether changes in hostility following treatment are primarily
      related to improvement in depressive symptoms or are also closely associated with
      reductions in negative thinking or perceived stress. We evaluated 94 outpatients
      with major depression before and after eight weeks of fluoxetine treatment by
      administering the Symptom Questionnaire (SQ) Hostility Scale, the Hamilton Rating
      Scale for Depression (HAM-D), the Cognitions Questionnaire (CQ) and the Perceived
      Stress Scale (PSS). We observed significant elevations in scores on these
      questionnaires in depressed patients as compared to normal controls. Following
      treatment with fluoxetine, there was a statistically significant reduction in
      scores on all four questionnaires. We observed that changes in SQ Hostility were
      significantly positively related to changes in both depression severity and
      perceived stress, with these relationships remaining significant after adjusting
      for gender and baseline SQ Hostility. The relationship between SQ Hostility
      changes and reductions in negative thinking became significant only after
      adjusting for gender and baseline SQ hostility. Our results suggest that the
      marked decrease in hostility following antidepressant treatment is related to a
      reduction in depressive symptoms, stress levels and negative thinking.

PMID- 9023790
TI  - Impaired binocular depth inversion in patients with alcohol withdrawal.
AB  - Binocular depth inversion represents an illusion of visual perception. Such
      inversion does not occur in all cases, especially when objects with a higher
      degree of familiarity (e.g. photographs of faces) are displayed. Cognitive
      factors are assumed to override the binocular disparity cues of stereopsis. We
      tested the hypothesis that during alcohol withdrawal the human CNS is unable to
      correct the implausible perceptual hypothesis. Measurements of binocular depth
      inversion in perception of 3D objects were performed in 10 patients with mild
      alcohol withdrawal and in 11 healthy volunteers. The binocular depth inversion
      scores were highly elevated in the patients group in comparison to the healthy
      volunteers. The data demonstrates a strong impairment of binocular depth
      inversion in alcohol withdrawal and support the view that alcohol withdrawal may
      be accompanied by a disorganization of the interaction between sensory input and
      generation of perceptual hypotheses.

PMID- 9023791
TI  - Relationship between impairment of prenatal brain growth and family history of
      psychosis in schizophrenia.
AB  - Recently McNeil et al. (1993b), showed that schizophrenics had smaller head
      circumference (HC) at birth than controls. This small head size at birth was
      observed more commonly among schizophrenics without a family history of psychosis
      than among familial schizophrenics, suggesting that some prenatal environmental
      factors, rather than genetic factors, are related to the impaired brain growth in
      utero. We attempted to replicate this finding in 100 Japanese schizophrenics (DSM
      III-R), using contemporaneous data on body measures at birth. Conversely, in the
      current study, HC at birth was found to be significantly smaller in
      schizophrenics with a family history of psychosis (N = 19) than those without (N
      = 81). A multiple regression analysis, controlling for gender, gestational age,
      maternal age, birth order and year of birth, yielded an overall reduction of
      about 1 cm in HC at birth among familial schizophrenics compared with non
      familial schizophrenics. When HC at birth in family history positive and negative
      groups was compared separately with the local population norms with adjustment
      for gender and gestational age, familial and non-familial schizophrenics were
      both found to have significantly smaller HC at birth, although the difference was
      less marked for the latter. These results suggest that schizophrenics have
      delayed cerebral development in utero, and that genes which operate on prenatal
      neurodevelopment may play an important role in the aetiology of schizophrenia,
      although it is possible that some environmental factors may also be involved in
      the impaired brain growth.

PMID- 9023792
TI  - Comparing correlated kappas by resampling: is one level of agreement
      significantly different from another?
AB  - Researchers comparing diagnostic systems or screening tests frequently need to
      compare indices of agreement such as the kappa coefficient. While asymptotic
      methods exist for comparing kappas derived from independent samples, no
      satisfactory approach exists for comparing kappas derived from the same or
      related samples. Resampling methods for comparing kappa coefficients obtained
      from the same sample are presented. Easily undertaken using readily available
      software, these methods are illustrated by application to a small sample of
      psychiatric data, as well as to several thousand samples of simulated data. An
      acceptable type I error rate was exhibited. Resampling techniques-easily
      implemented and making few assumptions-deserve wider application in psychiatric
      research.

PMID- 9023793
TI  - Interactive computer-based cognitive training in patients with Alzheimer's
      disease.
AB  - The present paper presents data from ten patients suffering from mild to moderate
      Alzheimer's disease (AD), all of whom were trained to use an interactive computer
      based program. Using photographs of the patient and his or her personal
      surroundings, an everyday task of relevance to the patient was simulated on a PC
      touch screen, which the patient was trained to operate. After three weeks of
      training (three to four sessions a week), the patients needed less help in
      performing the programs, they became faster, and eight out of ten made fewer
      mistakes. The results were most pronounced in patients with a poor performance at
      the beginning, and there was no difference between early-onset (EO) and late
      onset (LO) AD patients. Although the training was generally well received, there
      was no evidence of a general cognitive improvement, and it remains an open
      question whether the results achieved with PC training can be transferred to real
      life situations.

PMID- 9023794
TI  - Failings of the purchaser-provider split.

PMID- 9023795
TI  - Causes of death associated with psychiatric illness.
AB  - BACKGROUND: A prospective cohort analysis of mortality, among entrants to a
      population-based psychiatric case register, was undertaken to identify specific
      causes of death responsible for the increased risk of mortality previously
      reported in this large group of unselected patients. METHODS: The analysis was
      based on a study population of 16,871 cases, aged 15-89 years, from Worcester and
      Kidderminster Health Districts, entering the case register between 1974 and 1984
      and generating a total of 85,073 patient-years (PYR) of observation. The
      underlying cause of death was coded to the relevant revision of the International
      Classification of Diseases (ICD). Numbers of deaths observed in the study
      population were compared with the number of deaths expected on the basis of
      mortality rates for England and Wales. Comparisons were made for eight main
      causes of death, aggregated at Chapter level of the ICD, and 11 categories of
      psychiatric diagnoses. Two indices of mortality were used for evaluation:
      relative risk (RR) = observed deaths/expected deaths; and excess mortality rate
      (EMR) = (observed-expected deaths)/PYR. RESULTS: RRs were significantly raised
      for accidents, including suicides, as anticipated, and for various main causes of
      death. The increased risk of accidental death was found across the majority of
      the 11 psychiatric diagnostic groups although the EMRs were low at less than
      5/1000 PYR. Deaths from respiratory disorders gave rise to the highest RRs after
      accidental deaths, and were responsible for substantial excess mortality among in
      patients and patients with psychotic illnesses (especially dementia). The largest
      numbers of deaths of both sexes were due to diseases of the circulatory system,
      with a 40 per cent excess of observed over expected values in the whole series.
      The excess was due mainly to deaths of in-patients and of patients with psychotic
      diagnoses. No excess of deaths owing to neoplasms was found for either in
      patients or out-patient groups. CONCLUSIONS: The findings that psychiatric
      illness is associated with an increased risk of death from "natural' causes and
      that the level of risk was related to the severity and to the diagnostic category
      of the illness have implications for patterns of care and use of resources.

PMID- 9023796
TI  - Part I of Membership of the Faculty of Public Health Medicine (MFPHM). Trends
      over time and factors associated with success in recent years.
AB  - BACKGROUND: The examination for Membership of the Faculty of Public Health
      Medicine (MFPHM) Part I, has been held for nearly 20 years. It aims 'to test the
      candidate's knowledge and understanding of the basic sciences of public health'.
      This paper presents simple statistics from the earliest years up to June 1995 and
      additional information on more recent sittings. METHOD: The number of people
      taking the examination and the proportion passing were obtained for every sitting
      from February 1978 to June 1995. Further data have been extracted for all
      sittings of the examination since the current regulations were introduced. The
      variables included were pass or fail as the outcome variable, date of birth,
      gender of candidate, postgraduate qualifications, present post of employer, and
      attendance at a formal academic course. RESULTS: The number of candidates has
      ranged from 12 to 115, the proportion passing from 42 per cent to 93 per cent.
      During the period from June 1992 to June 1995, 472 people applied to sit the
      examination. Of these 33 withdrew, leaving 439 person attempts. The overall
      proportion passing was 270/439 (61.5 per cent). Factors associated with success
      include being female, being a UK graduate, attending an academic course and
      having more experience in the specialty. CONCLUSION: Candidates and their tutors
      are reminded of the need for adequate preparation for the examination. The
      authors welcome comments on how monitoring should be carried out in the future.

PMID- 9023797
TI  - The prevalence of and risk factors for neck pain in Hong Kong Chinese.
AB  - BACKGROUND: Neck pain has been found to be a prevalent musculoskeletal complaint
      among Caucasians living in Europe and North America. The prevalence of and risk
      factors for this condition have not been studied among Chinese living in
      urbanised cities. The objective of this study was to describe the prevalence of
      and risk factors for neck pain in Hong Kong Chinese. METHODS: A household survey
      was conducted in two housing blocks, one being government-subvented housing and
      the other being private housing. Eight hundred men and women who were 30 years
      and older were interviewed on the occurrence and characteristics of neck pain,
      occupations and recreational activities. The life-time and one-year prevalence of
      neck pain were calculated, and the odds ratio (OR) and 95 per cent confidence
      intervals (95 per cent CI) for various risk factors were derived by logistic
      regression. RESULTS: The one-year prevalence of neck pain was 15 per cent and 17
      per cent in men and women, respectively. The OR was 1.6 (95 per cent CI = 1.2
      2.4) for living in private housing and 2.1 (95 per cent CI = 1.1-4.0) for working
      as managers and professionals. Subjects with neck pain spent more time reading
      and a history of trauma to the neck was a significant risk factor for subsequent
      pain (OR = 5.6, 95 per cent CI = 3.3-9.4). CONCLUSION: Neck pain is a prevalent
      problem in Hong Kong Chinese, particularly among subjects of a high socioeconomic
      status. There was little association between life-style and neck pain, although
      subjects with neck pain spent more time in reading.

PMID- 9023798
TI  - Regional variations in the utilization rate of vaginal and abdominal
      hysterectomies in the United Kingdom.
AB  - BACKGROUND: Large geographic variations in hysterectomy rates are well known;
      however, very little is known about geographic variations in the route of the
      procedure, i.e. whether it is performed abdominally or vaginally. We compared
      utilization rates for abdominal and vaginal hysterectomies for the 14 Regional
      Health Authorities of England, and Northern Ireland over a three-year period.
      METHODS: Data were collected in the form of hospital episode statistics and small
      area analysis techniques were used to document regional variations. RESULTS:
      Large regional differences in the utilization of vaginal hysterectomies were
      recorded. Three areas in particular (Northern Ireland, Yorkshire and NW Thames)
      displayed high vaginal to abdominal ratios. Northern Ireland recorded the highest
      ratio (0.366), Mersey Regional Health Authority the lowest (0.139). The use of
      the vaginal route was found to increase with age, and was the most common route
      for the > 65 years age group. CONCLUSION: Despite an increasing volume of
      evidence advocating the use of the vaginal route, there appears to be a
      resistance to its use, except in older women. The role of physician practice
      style, and in particular group clinical judgement, is highlighted as being
      significantly involved in explaining the observed geographic variations.

PMID- 9023799
TI  - Promoting breastfeeding: a view of the current position and a proposed agenda for
      action in Scotland.
AB  - The prevalence of breastfeeding in Scotland is the second lowest in Europe. There
      is good evidence that breastfeeding results in decreased gastrointestinal, and to
      a lesser extent respiratory infections, in the first year of life, and reduced
      serious infections in low-birthweight babies. Published evidence for the
      effectiveness of interventions which seek to promote successful breastfeeding
      within populations is scanty and of poor quality, although numerous studies have
      highlighted hospital practices which discourage and undermine breastfeeding.
      Changing these poor practices has been shown to be achievable and can lead to
      improved breastfeeding rates. Experience in other industrialized countries such
      as Canada, Australia and Norway has shown that substantial increases in
      breastfeeding are achievable through combined government and health service
      action over a period of one or two decades. We recommend a combination of
      government and health service action to promote breastfeeding in Scotland
      including: implementation of the International Code on Marketing of Breastmilk
      Substitutes; reviews of health professional basic and in-service training in
      breastfeeding management, maternity leave and allowances, and workplace
      facilities for breastfeeding mothers; promotion of the Baby Friendly Initiative;
      development of community support for breastfeeding mothers; routine collection of
      breastfeeding data to support annual monitoring of breastfeeding rates; and
      support for research on the effectiveness of strategies which seek to promote
      breastfeeding.

PMID- 9023800
TI  - The costs and effectiveness of surveillance of communicable disease: a case study
      of HIV and AIDS in England and Wales.
AB  - BACKGROUND: In England and Wales, surveillance of communicable disease is carried
      out and co-ordinated by the Public Health Laboratory Service (PHLS). The
      surveillance of HIV infection and AIDS is undertaken by the PHLS AIDS Centre at
      the Communicable Disease Surveillance Centre (CDSC). Epidemiological data derived
      from surveillance are not, however, a free good: they are a resource with an
      associated opportunity cost and should therefore be open to economic appraisal
      alongside other users of health care resources such as medical interventions.
      This paper assembles information on the current surveillance of HIV and AIDS in
      England and Wales, and explores methods for performing an economic evaluation of
      such activities. METHODS: An examination of the cost and effectiveness of the
      PHLS AIDS Centre's epidemiological surveillance mechanisms for HIV and AIDS in
      England and Wales was undertaken. The total costs of each component of
      surveillance of HIV and AIDS in England and Wales were calculated. Two categories
      of cost were estimated: peripheral costs incurred by reporters in reporting AIDS
      cases or HIV infections or by laboratories in collecting samples; and central
      costs incurred by the PHLS AIDS Centre in processing and analysing incoming data.
      Using these cost data and information from a cost-effectiveness register, the
      additional health gains that would have to be obtained from surveillance to make
      the programme broadly cost-effective in comparison with other accepted uses of
      health service resources were then estimated. RESULTS: In the financial year 1993
      1994 the total costs of surveillance were estimated to be 1.4 million pounds. To
      avoid being considered relatively cost-ineffective at least 3.5 infections per
      annum need to be averted. To be considered favourably cost-effective,
      approximately 9.5 infections per annum need to be averted. CONCLUSIONS: In 1993
      1994, expenditure on surveillance of HIV and AIDS accounted for less than 1 per
      cent of the total allocation of resources to the National Health Service for all
      HIV and AIDS activities. Given these cost estimates, the number of infections
      which surveillance would have to contribute towards preventing in order to be
      considered cost-effective is low.

PMID- 9023802
TI  - Assessing the risk from environmental cadmium exposure.
AB  - BACKGROUND: Previous soil surveys by Environmental Health Officers had found high
      soil cadmium (Cd) concentrations in gardens next to a battery factory in
      Worcestershire. This study was set up to determine whether this had resulted in
      high Cd levels in the blood and urine of local residents. METHODS: A sample of
      residents (n = 39) living next to the factory were matched by age and sex to
      employees of North Worcestershire Health Authority. A questionnaire was used to
      determine potential Cd exposure. The levels of Cd in blood, urine and garden soil
      were measured. RESULTS: None of the members of the study group had a blood or
      urine Cd concentration above the levels estimated to cause harm. Only one member
      of the comparison group, but all members of the study group, had soil in their
      gardens with a Cd concentration above the recommended level. Adjusting for
      smoking status and other confounders by using logistic regressional analysis
      showed that being in the study group did not confer a greater risk of having an
      elevated blood or urine Cd concentration. The greatest influence on Cd
      concentrations was a current smoking habit. CONCLUSIONS: No evidence was found to
      show that the high soil cadmium concentrations had adversely affected the health
      of local residents. Specific issues raised during the implementation of this
      study were the resource implications of assessing environmental exposure and the
      difficulties in recruiting the study group. Health Authorities and local
      government need to be fully aware of similar problems they might encounter before
      investigating a potential environmental health hazard.

PMID- 9023801
TI  - The prevention and management of stroke.
AB  - The Government's Health of the nation strategy demands a reduction in the level
      of ill-health and death caused by stroke. This review describes the present state
      of knowledge on the prevention and management of stroke. Effective intervention
      in stroke has a number of major implications, including: health education for the
      public; education of health professionals (general practitioners, consultants and
      others); availability of guidelines and protocols; access to specialist advice,
      investigations and their interpretation, and rapid treatment, including surgery;
      availability of specially trained nurses for screening and monitoring; and
      availability of specialist multidisciplinary teams in hospitals and the
      community.

PMID- 9023803
TI  - Adolescents' use of prescribed drugs and over-the-counter preparations.
AB  - BACKGROUND: The objectives of this paper are to present data on the self-reported
      use of prescribed and over-the-counter drugs among young people aged 11-12 and 14
      15 years and to examine factors associated with the use of prescribed drugs, over
      the-counter painkillers and cough and cold treatments. METHOD: Data were
      collected from a representative sample of pupils aged 11-12 years old and 14-15
      years old attending 85 schools in Trent Region. Results are based on replies from
      approximately 8500 pupils in each year group. Pupils were asked to self-report
      usage by ticking a list of prescribed and non-prescribed drugs or medicines.
      RESULTS: Girls aged 14-15 years are more likely than others to have used at least
      one of the drugs in the previous week, with 40 per cent of girls in this age
      group having used a non-prescribed painkiller. Young people with a long-term
      illness or previous injuries are more likely to report having used prescribed
      drugs and/or over-the-counter painkillers. Family car-ownership, a proxy for
      socio-economic status, is not associated with the use of those drugs examined in
      more detail. CONCLUSIONS: The levels of use of over-the-counter drugs,
      particularly those with potential side effects, indicate that further studies are
      needed to examine patterns of use in more detail and that health education about
      self-medication is appropriate among young people aged 11-12 years and above.

PMID- 9023804
TI  - Provision of environmental control systems in the north west of England.
AB  - BACKGROUND: Environmental control systems (ECS) enhance the independence of
      housebound severely physically disabled people and offer them the prospect of a
      greater quality of life. A Department of Health scheme has provided ECS to
      severely disabled people. Provision and quality of provision in the North West
      were examined. METHODS: Audit of five years' prescriptions within the North West
      of England was carried out. Postal questionnaires were sent to 41 voluntary and
      self-help groups. Additional qualitative data were collected by contacting
      manufacturers and voluntary group advisors. RESULTS: Eighty per cent of people
      referred for assessment received an ECS. However, there was geographical
      variation in referral rates and a bias toward younger people. There were
      unexplained variations among the assessors. The commonest diagnoses resulting in
      referral were multiple sclerosis, motor neurone disease and muscular dystrophy.
      Many other conditions, such as stroke and arthritis, for which an ECS might
      produce benefit were under-represented. There were some problems with the quality
      of the service, especially with the timescale of provision. CONCLUSION: It is
      concluded that doctors and other professionals need a heightened awareness of the
      categories of person who can benefit from an ECS. Clarification of criteria and
      training are required if assessors are to be more consistent. Moreover, the
      mechanism of provision needs review. Public health physicians should re-evaluate
      their roles in provision, and should concentrate on commissioning an appropriate
      and good quality service rather than on co-ordination of the scheme.

PMID- 9023805
TI  - Setting targets for CABG surgery in the north western region.
AB  - BACKGROUND: A national target for coronary artery bypass graft (CABG) operations
      of 300 per million population was established by the Department of Health in
      1987. Regional Health Authorities were required in 1993-1994 to achieve this
      target. The 1990-1991 Regional all-ages CABG rate was 239 per million population.
      The North Western Region planned to devolve the purchasing of certain services,
      including cardiac surgery, to districts in April 1993. Three districts had
      provider units within their boundaries. No means existed for estimating the
      appropriate operation rate, according to need, for district populations. A method
      was therefore devised for calculating guideline targets. METHODS: Based on the
      assumption that the ischaemic heart disease standardized mortality ratio (IHD
      SMR) is a valid proxy of the need for CABG operations and using a linear
      regression model, the existing district IHD SMRs and IHD hospitalization rates
      were used to derive guideline targets for districts, taking account of the need
      to raise the average operation rate for the Region to 300 per million population.
      Further targets using alternative Poisson regression model and weighting formulae
      were also derived. RESULTS: The derived operation targets based on the linear
      regression model were lower than the existing operation rate in the three
      provider districts and in the biggest provider's two neighbours. In all other
      districts, except one, targets were higher than the existing number of
      operations. The two further analyses produced essentially similar results.
      CONCLUSIONS: In the North Western Region wide variations in CABG operation rates
      existed. Access to CABG surgery in the North Western Region appears to depend on
      proximity to the provider districts. Operation rates should reflect need. This
      paper presents a method for deriving targets which take account of need.

PMID- 9023806
TI  - The use and cost of hospital services by London AIDS patients with different AIDS
      defining conditions.
AB  - BACKGROUND: Contracting for HIV service provision is now an established part of
      the National Health Service commissioning process. AIDS is a heterogeneous
      condition, comprising various opportunistic illnesses which require different
      services and which have different resource implications. This study describes the
      use of hospital services and associated costs for the management of different
      AIDS defining conditions. METHOD: A retrospective case-notes analysis was
      performed, of 335 AIDS patients treated at St Mary's Hospital, London, between 1
      January 1983 and 30 September 1989, as well as a costing exercise of 37 clinical
      departments to calculate HIV-related costs. RESULTS: Mean age at time of AIDS
      diagnosis for these predominantly homosexual men was 38 years. Use of services
      varied, as did associated costs-from 8163 pounds per patient-year for patients
      with Constitutional Disease to 42,124 pounds for those with Cytomegalovirus
      Disease Most diagnostic categories showed a shift over the study period from an
      in-patient- to an out-patient-based service. Patients diagnosed after 1987 had
      overall lower costs per patient-year compared with those diagnosed before 1987:
      whereas out-patient costs for most groups had increased, in-patient expenditure
      decreased. For most categories, in-patient care costs and out-patient drugs
      prescribed provided the greatest proportion of total costs. Average costs per in
      patient day ranged from 334 pounds to 433 pounds, and average costs per out
      patient visit ranged from 99 pounds to 411 pounds for different AIDS defining
      conditions. CONCLUSIONS: Different opportunistic illnesses of symptomatic HIV
      disease have different treatment and resource implications. Casemix will need to
      be taken into consideration when contracting for HIV services, including extra
      contractual referrals.

PMID- 9023807
TI  - The public health uses of the Scottish Community Health Index (CHI).
AB  - Each of the 15 Health Boards in Scotland maintains a computer file of its
      residents who are registered with a general practitioner; this is known as the
      Community Health Index or CHI. The CHI allows a variety of demographic data and
      indicators of health to be analysed on either a geographic or general practice
      base, or both simultaneously. The considerable potential of the CHI as a public
      health tool may be of interest to health authorities outside Scotland which are
      developing wider uses for their own family practitioner registers.

PMID- 9023808
TI  - Building health promotion into health care reform in Russia.
AB  - The health care system of the former Soviet Union, despite serious flaws, did
      provide the basis for community health activities, and for mandatory immunization
      and periodic health examinations for which primary care physicians were
      responsible. Since 1991, a new system of mandatory health insurance has been put
      into place. Health care funding has decreased substantially, owing to economic
      conditions. However, there is not yet widespread acceptance either of the strong
      association between personal behaviour and health consequences, nor of the
      importance of individual responsibility for one's health. To summarize, efforts
      at health promotion and disease prevention in Russia face numerous barriers:
      severe financial constraints owing to the general economic situation; social
      upheaval with loss of previous constraints on behaviour; cultural characteristics
      that include fatalism and encouragement of heavy alcohol and tobacco consumption;
      lack of acceptance of individual responsibility for health; lack of role
      modelling by the medical community; lack of critical appraisal of benefit and
      cost-effectiveness for preventive interventions; low priority for health care,
      and for prevention specifically. Disease prevention and health education must be
      built into the reformed health care system, to promote health for the Russian
      population.

PMID- 9023809
TI  - Cardiac rehabilitation in Scotland: is current provision satisfactory?
AB  - BACKGROUND: Cardiac rehabilitation is an effective intervention, lowering
      mortality following myocardial infarction and reducing morbidity in patients with
      coronary heart disease. However, its level of provision was unclear. This study
      aimed to provide a comprehensive description in Scotland. METHODS: A national
      survey of hospital, general practice and community sources was conducted in 1994
      to identify cardiac rehabilitation programmes in Scotland. Detailed information
      about each programme was collected by computer-assisted telephone interviews.
      RESULTS: Sixty-nine programmes were identified, providing out-patient cardiac
      rehabilitation to 4980 patients and in-patient cardiac rehabilitation to 8920
      patients. This represented 17 per cent and 30 per cent of patients admitted to
      hospital with coronary heart disease (excluding heart failure), respectively.
      There was considerable geographical variation in provision and dependence on
      sources outside the health service for much funding. CONCLUSIONS: Despite
      evidence of benefits from randomized trials, the overall provision of cardiac
      rehabilitation in Scotland was low. Considerable inequity was demonstrated
      between different health board areas. There is opportunity for better provision,
      which would improve care for many patients with coronary heart disease.

PMID- 9023810
TI  - Quarterly Communicable Disease Review April to June 1996. From the PHLS
      Communicable Disease Surveillance Centre.

PMID- 9023811
TI  - Screening and the new genetics: a public health perspective on the ethical
      debate.

PMID- 9023812
TI  - Anorectal disease: risk factors and delay in presentation in the United Arab
      Emirates.

PMID- 9023813
TI  - A pilot study of the use of clinical guidelines to determine appropriateness of
      patient placement on intensive and high dependency care units.

PMID- 9023814
TI  - Is there a Th2 bias in human pregnancy?

PMID- 9023815
TI  - There is a bias against type 1 (inflammatory) cytokine expression and function in
      pregnancy.

PMID- 9023816
TI  - Population genetic studies of HLA-G: allele frequencies and linkage
      disequilibrium with HLA-A1.
AB  - HLA-G is a class I gene that is expressed in the extravillous cytotrophoblast.
      Although the function of this gene is still unknown, its expression at the
      maternal-fetal interface suggests that HLA-G may play a key role in the induction
      of tolerance during pregnancy. Preliminary to our studies of the effects of HLA-G
      polymorphisms on pregnancy outcome, we have defined HLA-G alleles in the
      Hutterites. We report here the presence of nine HLA-G alleles that differ with
      respect to nucleotide sequences, including four groups of alleles that differ
      with respect to amino acid sequences, and striking linkage disequilibrium between
      HLA-G and HLA-A alleles. The levels and sites of polymorphism in HLA-G suggest
      that this gene had a unique evolutionary history and may perform nonclassical
      functions at the maternal-fetal interface.

PMID- 9023817
TI  - Differential regulation of TGF-beta 2 by hormones in rat uterus and mammary
      gland.
AB  - Previous work from this laboratory has shown that transforming growth factor beta
      2 (TGF-beta 2) mRNA is abundant in the pregnant uterus. In the present study, we
      examined the synthesis and secretion of TGF-beta 1,2 and 3 in the rat uterus and
      mammary gland and show differential secretion and expression of TGF-beta 2 in a
      tissue specific manner. Elevated levels of TGF-beta 2 were detected in late
      pregnant maternal plasmas (> 100 pM), and in the milk (> 500 pM) during early
      lactation. High concentrations of TGF-beta 2 (> 200 pM) were also detected in
      uterine fluids collected from ovariectomized adult rats after high dose estrogen
      treatment. TGF-beta 2 mRNA levels were elevated in lobuloalveolar epithelial
      cells isolated from pregnant mammary gland. Three major transcripts of 3.5, 4.0,
      and 4.7 kb were seen, of which the 4.7 kb, dominates. Mammary glands of estrogen
      treated ovariectomized rats showed a similar pattern of TGF-beta 2 transcripts.
      In contrast, four major TGF-beta 2 mRNA transcripts of 5.7, 4.7, 4.0, and 3.5 kb,
      with the dominant species of 4.0 and 5.7 kb, were observed in uteri from the
      estrogen treated animals up to 48 h after the last estrogen injection. This
      suggests that TGF-beta 2 is regulated in a tissue specific manner. We conclude
      that the secretion of TGF-beta 2 is tightly regulated by hormones and that
      estrogen and prolactin are critical factors in the tissue-specific regulation of
      the local production of TGF-beta 2 in the mammary gland and female reproductive
      tract.

PMID- 9023818
TI  - Transfer of heterologous immunoglobulin into the uterine lumen of pigs.
AB  - Transfer of circulating heterologous immunoglobulin G (IgG) into the uterine
      lumen of pigs has not been reported. The present study determined if ovine IgG
      (oIgG) could be transferred into the uterine lumen of pigs. Six gilts (nonparous
      female pigs) were injected i.v. with either immune sheep serum (25 or 50 ml) to
      porcine uteroferrin (Uf) or non-immune sheep serum (50 ml) on days 9, 11 and 13
      of the estrous cycle. Serum was collected daily from days 9 to 15 and uterine
      flushings were collected at hysterectomy on day 15. An ELISA detecting oIgG was
      used to determine levels of oIgG in pig sera and uterine flushings. High oIgG
      levels in serum (ranging from 87 +/- 11 to 141 +/- 14 micrograms/ml) were
      maintained by injecting the gilts at 48 h intervals with ovine antiserum to
      porcine Uf. Serum concentrations of oIgG did not differ (P > 0.05) regardless of
      whether immune or non-immune sera or different doses of immune serum were
      injected. oIgG in uterine flushings (2 +/- 1 micrograms/uterine flushing) was
      detectable when the samples were concentrated 40-fold, but were lower (P < 0.01)
      than serum levels of oIgG (107 +/- 10 micrograms/ml). Results indicate that small
      amounts of circulating heterologous IgG can be transferred into the uterine lumen
      of pigs. However, passive immunization may not result in titers high enough to
      examine in vivo functions of proteins secreted into the uterine lumen of pigs.

PMID- 9023819
TI  - TNF alpha concentrations and mRNA expression are increased in preeclamptic
      placentas.
AB  - Tumor necrosis factor-alpha (TNF alpha), a cytokine produced mainly by
      macrophages, is involved in immunoregulation, the modulation of cell growth and
      differentiation, as well as in the induction of oxygen free radicals. In
      preeclamptic placentas, lipid peroxides are increased as compared to normal
      placentas. If TNF alpha was abnormally increased in preeclamptic placentas, it
      might contribute to the increased oxidative stress and the formation of lipid
      peroxides. We hypothesized that TNF alpha levels would be higher in preeclamptic
      than in normal placentas. We determined: (1) the levels of TNF alpha protein in
      whole placental tissue; (2) the concentrations of TNF alpha protein and lipid
      peroxides in the medium after 48 h of incubation of whole placental villi; (3)
      mRNA expression of TNF alpha. Placental TNF alpha protein levels were measured by
      ELISA, lipid peroxides by a spectrophotometric method specific for peroxides, and
      TNF alpha mRNA expression by RT-PCR. RESULTS: (1) TNF alpha tissue levels were
      significantly higher in preeclamptic than in normal placentas, P < 0.05. (2)
      Concentrations of both TNF alpha and lipid peroxides were higher in the
      incubation medium of preeclamptic than normal placentas, P < 0.05. (3) TNF alpha
      concentrations in the incubation medium were positively correlated with lipid
      peroxide concentrations, r = 0.608. (4) TNF alpha mRNA was expressed in
      preeclamptic placentas, but not in normal placentas. CONCLUSIONS: TNF alpha
      protein concentrations and mRNA expression are higher in preeclamptic than normal
      placentas and this is associated with increased lipid peroxidation.

PMID- 9023820
TI  - Characterization of anti-sperm antibodies and their coding cDNA sequences by
      Epstein-Barr virus transformed B cell lines from lymphocytes of infertile women
      possessing anti-sperm antibodies.
AB  - Epstein-Barr virus (EBV)-transformed B cell lines that produce human antisperm
      antibodies were established using peripheral blood lymphocytes (PBLs) from
      infertile women with sperm immobilizing antibodies in their sera. We obtained
      three stable cell populations (designated B1, B2, D5) of transformed PBLs
      originating from three different patients. They produced IgM sperm-reacting
      antibodies directed against the tail of live, methanol-fixed and NaIO4-treated
      human spermatozoa. The established antisperm antibodies recognized
      noncarbohydrate sperm membrane antigens with different specificity and
      distribution in the male reproductive system. Antisperm antibody-B2 corresponding
      antigen appears to be specific for the male reproductive system. This antigen is
      excreted from the epithelial cells of the ductus epididymidis and bound to the
      spermatozoa in the lumen of the ductus. Antisperm antibodies B1 and D5
      corresponding antigens were expressed on the spermatozoa in the seminiferous
      tubules and were common to the secretions of the ductus epididymidis, prostate
      and some other somatic organs. The cDNA of the immunoglobulin heavy chain genes
      were analyzed by reverse transcription polymerase chain reaction (RT-PCR) using
      RNA extracted from these clones. The immunoglobulin heavy chain cDNA sequences of
      these antisperm antibodies showed extremely high homology to previously reported
      immunoglobulin germline DNA sequences, implying that these antisperm antibodies
      might be natural autoantibodies rather than antibodies stimulated by external
      antigen.

PMID- 9023821
TI  - National Institutes of Health Consensus Development Conference Statement:
      cervical cancer, April 1-3, 1996. National Institutes of Health Consensus
      Development Panel.
AB  - OBJECTIVE: The objective was to provide physicians and the general public with a
      responsible assessment of current screening, prevention, and treatment approaches
      to cervical cancer. PARTICIPANTS: A non-Federal, nonadvocate, 13-member panel
      representing the fields of obstetrics and gynecology, gynecologic oncology,
      radiation oncology, and epidemiology participated. In addition, 28 experts in
      obstetrics and gynecology, gynecologic oncology, radiation oncology, gynecologic
      surgery, and psychology presented data to the panel and a conference audience of
      500. EVIDENCE: The literature was searched through Medline, and an extensive
      bibliography of references was provided to the panel and the conference audience.
      Experts prepared abstracts with relevant citations from the literature.
      Scientific evidence was given precedence over clinical anecdotal experience.
      CONSENSUS PROCESS: The panel, answering predefined questions, developed their
      conclusions based on the scientific evidence presented in open forum and the
      scientific literature. The panel composed a draft statement that was read in its
      entirety and circulated to the experts and the audience for comment. Thereafter,
      the panel resolved conflicting recommendations and released a revised statement
      at the end of the conference. The panel finalized the revisions within a few
      weeks after the conference. CONCLUSIONS: Carcinoma of the cervix is causally
      related to infection with the human papillomavirus (HPV). Reducing the rate of
      HPV infection by changes in sexual behaviors in young people and/or through the
      development of an effective HPV vaccine would reduce the incidence of this
      disease. Papanicolaou smear screening remains the best available method of
      reducing the incidence of and mortality from invasive cervical cancer. Persons
      with stage IA1 disease have a high cure rate with either simple hysterectomy or,
      where fertility preservation is an issue, by cone biopsy with clear margins. For
      patients with other stage I or stage IIA disease, radical surgery or radiation
      treatment is equally effective. These patients should be carefully selected to
      receive one treatment or the other but not both, because their combined use
      substantially increases the cost of and morbidity from treatment. Women with more
      advanced, nonmetastatic disease should be treated with radiation. Recurrent
      cervical cancer confined to the pelvis should be treated with the modality not
      previously received. Radiation therapy is recommended to palliate symptoms in
      patients with metastatic disease.

PMID- 9023822
TI  - Epidemiology of cervical cancer.
AB  - Cervical cancer is a major public health problem through-out the world, and
      despite important declines in incidence and mortality observed in developed
      countries in the last 20 years, those indicators remain almost unchanged in
      developing countries. In addition, a recent increase in cervical cancer among
      women under age 50 years is being observed in some areas, particularly for
      adenocarcinoma, without a clear explanation. Marked socioeconomic and ethnic
      differences are evident in incidence, mortality, and survival from the disease,
      with the less affluent groups having a much higher impact. Epidemiologic research
      has concluded that certain types of human papillomaviruses are the central cause
      of cervical cancer and its precursors, and this has opened the door to the
      possibility of developing vaccines. However, many aspects of the epidemiology
      still need to be elucidated, and the development of clinically applicable
      vaccines will require a number of years to be achieved. Therefore, renewed
      efforts at improving screening programs are necessary, particularly among women
      in the lower socioeconomic regions and groups. In this paper, we present the
      descriptive epidemiology of invasive cervical cancer, with particular emphasis on
      the situation in the United States, based on the latest data from the National
      Cancer Institute's Surveillance, Epidemiology, and End Results Program (up to
      1992). In addition, a brief overview is made of current ideas on the role of
      human papillomaviruses and other risk factors for the disease.

PMID- 9023823
TI  - Screening patterns for cervical cancer: how best to reach the unscreened
      population.
AB  - Although the mortality rate for cervical cancer in the United States has declined
      steadily since the introduction of the Pap smear for screening in 1945, recent
      statistics show a rising incidence, with the number of new cases expected in 1996
      representing a record high since the mid-1980s. Part of the rising incidence may
      be because of increasing numbers of women in the United States who did not
      receive screening or having inadequate screening with the Pap smear. This paper
      will examine the recent patterns of cervical cancer screening in the United
      States, with particular attention to defining which populations are not being
      screened. Barriers to screening in these populations will be defined and grouped
      into four categories: lack of knowledge, economic, cultural, and belief system;
      and logistical. Successful approaches that have been used to overcome these
      barriers in screening programs targeted at the "hard to reach" population will be
      described.

PMID- 9023824
TI  - Cervical human papillomavirus infection and intraepithelial neoplasia: a review.
AB  - Cervical human papillomavirus (HPV) infections and intraepithelial neoplasias are
      precursors to cervical cancer, the second most common cancer in women worldwide.
      HPV satisfies the epidemiologic criteria for causality; the role of other
      cofactors is under study. Natural history studies show that most low-grade
      lesions (productive HPV infections) regress or persist, whereas high-grade
      lesions (those with integrated HPV DNA) progress. Immunobiologic studies
      demonstrate that infection peaks in the early 20s, leading to a 10- to 20-year
      period of persistent infection, before finally progressing to a preinvasive or
      invasive lesion. Papanicolaou (Pap) screening has lowered the morbidity and
      mortality from cervical cancer in every country in which screening programs have
      been introduced. The diagnostic strategy for an abnormal Pap smear includes
      colposcopy; the role of HPV DNA testing in screening or diagnosis remains
      unclear. Patients are treated with cervical ablation, cone biopsy, or
      chemopreventive agents. Efforts to strengthen screening and prevention, as well
      as new directions for research, are needed.

PMID- 9023825
TI  - Histopathologic prognostic factors in early stage cervical carcinoma.
AB  - The pathologist makes extensive assessments in cases of early stage carcinoma of
      the cervix. The following parameters are known to affect prognosis: capillary
      lymphatic space invasion, depth of invasion, size of gross tumor, histologic
      type, grade (in adenocarcinoma), involvement by tumor of pelvic or para-aortic
      lymph nodes, and lymphoid response and immune status. These findings, along with
      clinical stage, best predict tumor behavior. Other observations are under
      investigation to evaluate their usefulness.

PMID- 9023826
TI  - Integration of diagnostic imaging in the clinical management of cervical cancer.
AB  - Diagnostic imaging plays multiple roles during the initial assessment, treatment,
      and surveillance follow-up of patients with cervical cancer. Clarification of
      pretreatment disease extent aids in understanding prognosis, may influence
      selection of treatment modalities, and permits outcome comparison between
      different therapeutic interventions employed in similar groups of patients.
      Recently, use of historically important imaging assessments has declined
      precipitously, coincident with the increased use of contemporary imaging
      modalities not yet acknowledged by the International Federation of Gynecology and
      Obstetrics staging. In the United States, approximately 50% of the patients with
      invasive cancer will receive all, or a portion, of their initial treatment with
      radiation therapy. Clarification of the target volumes for radiotherapy,
      including both teletherapy and brachytherapy components, enables delivery of
      radiation therapy, with maximal confidence that all identifiable cancer is within
      the treatment field and normal tissues are excluded to the greatest extent
      possible. Imaging assessments can help select patients most likely to benefit
      from aggressive salvage therapies. Identification of sites of recurrence provides
      guidance for refinements in existing therapies and is an important element in the
      prospective evaluation of new treatments. As postmortem examination of patients
      who have died of cancer becomes a rare event, antemortem imaging can serve as an
      alternative to the traditional autopsy in determining cause of death and ultimate
      patterns of failure. Future challenges for diagnostic imaging include addressing
      the need for disciplined, prospective evaluation of emerging imaging technologies
      and, when sensible, rational integration of widely available, standardized
      imaging modalities into algorithms for initial staging and subsequent monitoring
      of patients treated for invasive cervical cancer.

PMID- 9023827
TI  - What is the appropriate management of early stage cervical cancer (International
      Federation of Gynecology and Obstetrics stages I and IIA), surgical assessment of
      lymph nodes, and role of therapeutic resection of lymph nodes involved with
      cancer?
AB  - It is well recognized that lesion size, tumor volume, depth of stromal invasion,
      and lymphatic space permeation are all important predictors of lymph node
      involvement in early stage cervical cancer. Pelvic lymph node involvement is the
      most important (negative) predictor of survival for these patients with early
      stage cervical cancer. The number of involved nodes and the size of involved and
      unresected nodes may also be prognostically significant. It is uncertain whether
      lesion size, tumor volume, depth of stromal invasion, or lymphatic space
      permeation are independent negative predictors of survival when correcting for
      lymph node positivity. Lymphadenectomy has traditionally been considered a
      diagnostic procedure. There is accumulating evidence to suggest that
      lymphadenectomy may have therapeutic benefit for patients with cervical cancer
      metastatic to lymph nodes. This hypothesis awaits further evidence.

PMID- 9023828
TI  - Management of stage IA cervical carcinoma.
AB  - Approximately 10%-15% of women with stage I cervical cancer have microinvasive
      lesions (stage IA). In studying these patients, we aim to identify the cancers
      that have little or no chance of harboring metastatic disease from the primary
      site. These patients may be treated by more conservative means, thereby lowering
      morbidity and cost and preserving the women's fertility. The diagnosis of stage I
      cervical cancer is surrounded by controversies concerning the diagnostic
      criteria, the low level of agreement among pathologists interpreting the same
      material, and the limited evidence in the literature for definitions of risk
      factors. The available information suggests that women with squamous cell lesions
      that invade at a 3-mm depth or less and who have no evidence of lymph-vascular
      invasion may be successfully treated with cervical conization. Women with a depth
      of invasion of more than 3 mm or with lymph-vascular invasion should be treated
      with methods that address the potential for disease in the lymph nodes and
      paravaginal tissues.

PMID- 9023829
TI  - Primary surgery for stage IB-IIA cervical cancer, including short-term and long
      term morbidity and treatment in pregnancy.
AB  - Radical hysterectomy and pelvic lymphadenectomy are indicated for the treatment
      of cervical carcinoma that is localized clinically to the cervix and upper
      vagina. Intraoperative complications have been reported in 1.1%-7.4% of patients.
      Long-term complications include bladder dysfunction (2% at 3 years), urinary
      fistula (vesical, 0.8%; ureteral, 1.2%), stress urinary incontinence (29%),
      ureteral stricture (1%), rectal dysfunction (80%), severe constipation (5.3%),
      lymphocysts (20% by ultrasonography; 2% clinically), and lymphedema (10%). The
      operative mortality is 0.7%. The 5-year survival rate for patients with stage IB
      disease is 85.7% and for stage IIA is 69.6%. The recurrence rate is 27.2%.
      Recurrences are distributed equally between the pelvis and extrapelvic sites.
      Radical hysterectomy is the treatment of choice for pregnant patients with early
      cervical cancer. It affords termination or delivery of the pregnancy at the same
      time that the treatment is provided. For patients with stage I disease treated
      with radical hysterectomy, the survival rate is 92.1%.

PMID- 9023830
TI  - Primary radiotherapy for stage IB or IIA cervical cancer.
AB  - Patients with carcinoma of the cervix (stages IB-IIA) have a tumor that is
      confined to the cervix and upper vagina. These patients, however, may have a
      tumor that ranges in diameter from less than 1 cm to as large as 10 cm. The
      survival for all patients with stage IB disease is 86%; for those with stage IIA
      disease, it is 72%. Reports of radiotherapy alone for small stage IB or IIA
      cervical cancer indicate a cure rate of greater than 90% and a severe
      complication rate of less than 5%. Bulky cervical cancers of stages IB-IIA
      treated with high doses of radiation have survival and complication rates that
      are dependent on tumor size, and no survival benefit has been demonstrated with
      the addition of a hysterectomy. Elective para-aortic irradiation has been
      demonstrated to be of benefit in this patient population. The quality of life for
      patients treated with radiotherapy alone depends on many factors.

PMID- 9023831
TI  - Stress and quality of life following cervical cancer.
AB  - Significant progress has been made in understanding the psychologic and
      behavioral aspects of cervical cancer. Descriptive data indicate acute trauma and
      disruption with the diagnosis and treatment, yet the majority of women return to
      precancer life. The notable exception to this is sexual functioning, which
      remains an area of significant morbidity. Future research will need to test
      variables that predict which women will be vulnerable to sexual dysfunction.
      Sexual self-concept (sexual self-schema), which is the extent to which a woman
      has a positive view of her own sexuality, appears to provide valuable
      information. The identification of such variables is an important step toward
      designing interventions for enhancing quality of life for patients with cervical
      cancer.

PMID- 9023832
TI  - New surgical approaches to treatment of cervical cancer.
AB  - PURPOSE: Our goal was to evaluate laparoscopic pelvic lymph node dissection, para
      aortic lymph node sampling, and laparoscopic radical vaginal hysterectomy
      (Schauta) in the treatment of early stage cervical cancer. MATERIALS AND METHODS:
      In a retrospective study of 37 patients treated in the period between October
      1993 and February 1996, we evaluated operative time, blood loss, length of
      hospital stay, lymph node count, and morbidity. Radical abdominal hysterectomy
      was compared with laparoscopic pelvic lymph node dissection and para-aortic lymph
      node sampling. Improvement over time was analyzed. RESULTS: Mean operative time
      was 225 minutes, blood loss was 525 mL, and the average hospital stay was 3 days.
      This information was compared with a radical abdominal hysterectomy and pelvic
      and para-aortic lymph node dissection, where the operative time was 210 minutes,
      blood loss was 1500 mL, and the hospital stay was 9.7 days. Blood transfusion was
      required in 11% of patients compared with a range of 35%-95% reported in the
      literature for radical abdominal hysterectomy. The mean pelvic lymph node count
      was 35; the mean para-aortic lymph node count was 11. Two patients had
      cystotomies repaired at surgery without lengthening hospital stay or subsequent
      complication. Two patients had ureteral vaginal fistulae treated by a ureteral
      stent, which was removed 6 weeks later without further operative procedures or
      urinary damage. When the data were correlated with the length of experience using
      the analysis of variance test and linear regression, operative time, blood loss,
      and hospital costs significantly improved over time. Patient charges averaged
      $14,868.00 and estimated hospital costs averaged $6449.00. CONCLUSION:
      Laparoscopic pelvic lymph node dissection and para-aortic lymph node sampling can
      be performed with adequate lymph node counts and lower morbidity. Laparoscopic
      Schauta allows shorter hospital stay than radical abdominal hysterectomy, with
      significantly less blood loss and markedly fewer blood transfusions. Morbidity is
      higher early in the surgeon's experience but decreases over time.

PMID- 9023833
TI  - Adjuvant therapy after primary surgery for stage I-IIA carcinoma of the cervix.
AB  - Radical hysterectomy and bilateral pelvic lymph node dissection is commonly used
      as a primary management option for treatment of stage IB/IIA carcinoma of the
      cervix. Overall cure rates approach 85%. However, a spectrum of relapse risk
      exists, depending on the presence or absence of primary tumor and nodal-related
      prognostic factors. Known factors include number and location of lymph nodes;
      size of primary, deep invasion in the cervix; capillary lymphatic space
      involvement; occult parametrial involvement; and positive or close surgical
      margins. Biologic determinants have yet to be identified. No systematic analysis
      has examined various combinations of prognostic factors to precisely define
      associated levels of risk and to predict the sites of relapse. Decreased local
      control and survival rates in some high-risk subgroups, usually those with nodal
      positivity, has led to the exploration of adjuvant therapies. Compiled data from
      retrospective series have defined the overall patterns of failure. Seventy-two
      percent of those relapsing have a component of pelvic failure, while 42%
      experience relapse in the pelvis alone. Fifty-eight percent have a component of
      distant failure but only 28% have distant disease alone. Adjuvant treatment
      options include pelvic radiotherapy, extended-field radiotherapy,
      chemoradiotherapy, and chemotherapy. Trials of adjuvant chemotherapy are too few
      to evaluate the use of available agents. Pelvic radiotherapy has been shown to
      reduce the relapse risk when surgical margins are close or positive. It also
      reduces the risk of pelvic relapse and improves the relapse-free interval but has
      no apparent impact on overall survival in the groups that have been selected for
      treatment. The apparent lack of benefit may relate to the choice of patients with
      nodal involvement who, despite high risk of pelvic failure, most likely have a
      predominant pattern of distant failure. Maximization of the survival benefit of
      pelvic radiotherapy requires the identification and treatment of the subgroup
      with a predominant pattern of pelvic failure, such as that examined in
      Gynecologic Oncology Group protocol 92. These may be patients with primary tumor
      related, high-risk factors but negative nodes. Extended-field irradiation for
      microscopically involved para-aortic nodes provides a cure in 25%-40% of the
      patients. Further studies of prognostic factors and their relationship to sites
      of failure after surgery are necessary to define the benefits of currently
      available adjuvant therapies with respect to local control, survival, and quality
      of life, and also to direct future studies. New, effective systemic agents are
      required for those at high risk of developing distant disease.

PMID- 9023834
TI  - Adjuvant surgery after radiotherapy.
AB  - Investigators disagree about the role of adjuvant hysterectomy after irradiation
      of bulky stage IB cervical carcinomas, although the benefit of combined treatment
      has never been clearly demonstrated. Studies that have correlated outcome with
      initial tumor diameter suggest that central recurrences are rare after
      irradiation of tumors less than 5 cm in diameter, leaving little room for
      improvement with additional local treatment. Early studies suggested that
      adjuvant hysterectomy may improve pelvic disease control for patients with bulky
      endocervical tumors, but these results may have reflected the selection of tumors
      with relatively favorable characteristics for combined treatment. Several studies
      have suggested that central pelvic disease can be controlled in more than 90% of
      patients with bulky endocervical tumors if they are treated with adequate doses
      of irradiation. Although published studies are somewhat limited by their
      retrospective designs, the available data do not support the added cost and
      morbidity of adjuvant hysterectomy in the routine treatment of patients with
      bulky early stage cervical carcinomas.

PMID- 9023835
TI  - Optimal management of locally advanced cervical carcinoma.
AB  - Locally advanced or recurrent cervical cancer is highly responsive to treatment
      and at least moderately curable with effective aggressive treatment. Radiation
      therapy is the mainstay of treatment for patients with this cancer. The roles for
      surgery and chemotherapy are as yet unproved, and both modalities are currently
      under investigation for their potential roles in the management of these
      conditions. Exenterative surgery clearly has an established utility for central
      pelvic failures after prior radiation therapy. Postsurgical pelvic recurrences
      are rarely successfully treated for cure, but considerable palliative effect is
      possible. The roles of intraoperative irradiation, sensitizing chemotherapy, and
      radical resection with interstitial irradiation are all under investigation at
      this time. Much has been learned over the past several decades about what
      parameters are important for successful radiation therapy for cervical cancers of
      stages IIB-IVA. While the traditional staging work-up for these patients included
      excretory urography, barium enema, examination under anesthesia, cystoscopy, and
      proctoscopy, there is now good evidence that computed tomography scan with
      intravenous contrast and office examination and biopsy are sufficient, with
      cystoscopy reserved for those few patients in whom clinical or imaging data
      suggest a higher risk of involvement. Surgical lymph node staging, especially of
      para-aortic lymph nodes, may be worthwhile in certain settings (e.g., for entry
      into research protocols), but it has no demonstrated role in routine clinical
      practice. Evidence is clear and convincing that effective treatment for these
      disease stages requires the inclusion of intracavitary brachytherapy. The role of
      interstitial brachytherapy is less clear, although there are some fervent
      advocates of this procedure. The debate continues about the use of low-dose-rate
      versus high-dose-rate brachytherapy. Treatment dose, volume, and length of
      treatment course are all important variables with outcome implications. The
      central disease requires a total dose of 8000-9000 cGy for maximal control
      probability, with larger tumors requiring the higher doses. The three-dimensional
      treatment volume must adequately surround the cancer and its likely routes of
      spread. Overall treatment time should be kept as short as possible, within the
      limits of conventional, tolerable fractionation. The potential theoretical
      advantage of hyperfractionated external-beam irradiation has yet to be verified
      in this disease but is of interest. It will be tested in an upcoming Gynecologic
      Oncology Group clinical trial. The negative prognostic significance of hypoxia in
      cervical cancers in general has been reported recently. While tumor cell hypoxia
      is almost certainly a problem in this disease, hypoxic cell sensitizers have not
      yet been found to improve treatment results. In clinical practice, reoxygenation
      probably occurs in these tumors. The role of paraaortic lymph node elective
      irradiation has been of interest for more than 20 years and was the subject of
      two randomized trials with quite different results. The Radiation Therapy
      Oncology Group trial found significantly improved survival in the treatment group
      assigned to receive paraaortic irradiation, when compared with the pelvic
      treatment group. However, a similar study by the European Organization for
      Research and Treatment of Cancer found no difference. The results of treatment
      today are substantially improved from those seen two decades ago. About 75% of
      patients with stage IIB disease and fully 50% of patients with stage IIIB disease
      are now cured with conventional irradiation alone. Clearly, there is still a need
      for further improvement. Of patients with urinary bladder involvement, 10%-20%
      are long-term survivors, as are 25%-30% of patients with para-aortic lymph node
      metastases. While these improvements are significant, there is clearly room for
      further progress. (ABSTRACT TRUNCATED)

PMID- 9023836
TI  - Neoadjuvant chemotherapy before surgery in cervical cancer.
AB  - Eighteen phase II clinical trials have demonstrated the relative ease of
      administering intravenous neoadjuvant chemotherapy before radical surgery in
      patients with cervical cancer. Toxicity has been modest, with the exception of
      occasional severe bleomycin-induced pulmonary toxic effects. All regimens tested
      have been cisplatin based with no clearly superior combination. Overall objective
      response rates were 85% for patients with International Federation of Obstetrics
      and Gynecology stage IB or IIA disease, 88% for those with stage IIB disease, 74%
      for those with stage III disease, and 47% for those with stage IV disease. There
      was a corresponding decrease in clinical complete response rates with increasing
      stage from 28% for those with stage IB or IIA disease to 7% for those with stage
      IV disease. Operability was also stage dependent: 94% for patients with stage IB
      and IIA disease, 74% for patients with stage IIB disease, and 58% for patients
      with stage III or IV disease. All inoperable patients received primary radiation
      therapy. Fifty-five percent of operable patients received postoperative radiation
      therapy. Most phase II trials using historical controls demonstrated comparable
      survival. Only a few trials showed improved survival with the use of neoadjuvant
      chemotherapy before radical surgery. To date, there has been only one reported
      prospective trial of neoadjuvant chemotherapy before surgery. Patients with stage
      IB disease were randomly assigned to receive radical hysterectomy and pelvic
      lymphadenectomy with or without neoadjuvant chemotherapy. A survival advantage
      was present only in patients with a tumor volume of greater than 60 cm3.
      Randomized, prospective trials of neoadjuvant chemotherapy followed by radiation
      therapy have shown either no advantage or a statistically significant reduction
      in survival when neoadjuvant chemotherapy is administered before radiation
      therapy. In light of this finding and the operability of only 58% of the patients
      with stage III or IV disease, it would be prudent to limit neoadjuvant trials to
      patients with stage I or II disease with an initial tumor volume of greater than
      60 cm3. Four such trials either are under way or are approved an awaiting
      activation.

PMID- 9023837
TI  - Concomitant and neoadjuvant chemotherapy in conjunction with radiotherapy in the
      management of locally advanced cervical cancer.
AB  - Radiotherapy is standard treatment for women with locally advanced cervical
      cancer (stage IIB-IVA). Radiotherapy fails to control disease progression within
      the irradiated field in more than 40% of patients. The disease bulk is a major
      factor limiting the curative probability of pelvic radiotherapy. Chemotherapy has
      been integrated with pelvic radiotherapy with the goal of improving local tumor
      control and treating microscopic metastases outside the radiotherapy field.
      Simultaneous chemotherapy and radiotherapy, neoadjuvant chemotherapy followed by
      radiotherapy, and adjuvant chemotherapy after radiotherapy, have been
      investigated. Hydroxyurea during pelvic radiotherapy has been reported to be
      associated with an improved progression-free (P = .05) and survival (P = .066)
      advantage. Several randomized trials of concomitant radiotherapy with
      fluorouracil, mitomycin, or cisplatin have been completed, but no results are
      published. Neoadjuvant chemotherapy with cisplatin-containing regimens followed
      by radiotherapy has been studied in several randomized trials. Although tumor
      response after chemotherapy is reported in more than 50% of patients, no
      improvement in local disease control or in survival has been noted overall. In
      one large trial, neoadjuvant chemotherapy was inferior to standard pelvic
      radiotherapy in terms of local control and survival. Adjuvant chemotherapy after
      radiotherapy has been little studied, and no randomized trials have been
      reported. The results of trials in progress or completed but not yet reported
      will determine further clinical research directions. Chemotherapy during and
      after pelvic radiation therapy has been little studied.

PMID- 9023838
TI  - Is there a radiobiologic basis for improving the treatment of advanced stage
      cervical cancer?
AB  - The success of radiotherapy in eradicating the primary tumor in patients with
      locally advanced cervical cancer is limited by normal tissue tolerance.
      Systematic recording of morbidity and treatment parameters is therefore very
      important for radiobiologic treatment optimization and clinical decision making.
      There is substantial evidence that fractionation schedules employing large doses
      per fraction lead to a loss of therapeutic ratio. A similar argument could be
      used for high-dose-rate (HDR) brachytherapy that should also be administered in
      small dose fractions. However, HDR brachytherapy might convey some advantage to
      physical dose distribution that should be weighed against the radiobiologic
      advantages of low-dose-rate (LDR) continuous irradiation. Increasing overall
      treatment time reduces local control probability, whereas a shorter overall
      treatment time by accelerated fractionation may improve the therapeutic ratio, at
      least in fast-growing tumors. Hypoxia and reduced oxygen delivery are associated
      with poor radiation response. Anemia should be compensated, if necessary. The
      role of hypoxic modification needs to be further explored. In the future, the
      therapeutic ratio may also be improved by the use of chemical and biologic
      response modifiers. Tumors are heterogeneous with respect to intrinsic
      radiosensitivity, proliferation parameters, and extent of hypoxia. Until a
      detailed prognostic profile can be obtained for each patient, optimal curative
      radiotherapy must aim for a sufficient dose, short overall treatment time,
      hypoxic modification, and LDR or low dose per fraction.

PMID- 9023839
TI  - Radiotherapy for the treatment of locally recurrent cervical cancer.
AB  - Following radical hysterectomy for stage I-IIA cervical carcinoma, 10%-15% of
      women will have a recurrence. Sixty percent of these recurrences will be located
      in the pelvis alone. The treatment of a localized pelvic recurrence depends on a
      number of factors, but primarily the history of previous radiation therapy (RT)
      to the pelvis and the location of the recurrence. For patients without a history
      of prior treatment, RT with or without chemotherapy can lead to disease-free
      survival rates of 20%-50% and local control rates of 20%-60%, and should be
      considered first-line treatment. For those with a history of previous RT and
      sidewall or nodal recurrences, a combination of surgery and brachytherapy or
      intraoperative radiotherapy may improve survival for these women who were
      previously considered incurable. However, this requires special expertise and
      technology not available at most centers.

PMID- 9023841
TI  - Chemotherapy for stage IVB or recurrent cancer of the uterine cervix.
AB  - Numerous drugs and drug combinations have been evaluated, largely in phase II
      trials, for the treatment of carcinoma of the uterine cervix. There clearly is a
      need for effective chemotherapy for this disease, but the results to date have
      unfortunately not met that need. Cisplatin is active but overrated. Drug
      combinations have not shown a consistent advantage and require careful study,
      with the initial focus on maximizing the complete response rate in women with no
      or minimal prior chemotherapy and with adequate sample size to have confidence
      about the results. The patient populations under treatment need to be carefully
      defined with respect to potential prognostic factors for response and survival,
      so that results will be more reproducible. The few large, randomized trials
      completed so far have failed to show a survival benefit with combination
      chemotherapy; in fact, there does not appear to have been a comparison of
      chemotherapy with best supportive care. Systemic therapy of cervical cancer
      remains experimental.

PMID- 9023840
TI  - Surgery for the treatment of locally recurrent disease.
AB  - BACKGROUND AND METHODS: Total pelvic exenteration is a salvage procedure done in
      the effort to eliminate completely pelvic cancer. Low colorectal anastomosis and
      continent urinary diversion are two new procedures that allow complete pelvic
      evisceration without the need for external appliances. From 1984 through 1994, 67
      patients have undergone rectosigmoid colectomy and low-colorectal anastomosis.
      Sixteen patients underwent surgery as part of a total pelvic exenteration for
      recurrent cervical cancer, and 51 patients underwent surgery for either primary
      or recurrent ovarian carcinoma as part of an optimal debulking procedure. Between
      1988 and 1995, 55 patients have received continent urinary diversion with the
      Miami Pouch. Fifty-two patients underwent surgery for recurrent cervical cancer,
      two patients for advanced vulvar cancer, and one patient for a vesico-vaginal
      fistula. All of the patients with recurrent cervical cancer had previously
      received radiation therapy for gynecologic cancer. RESULTS: Of the 16 patients
      with recurrent cervical cancer who had a low colorectal anastomosis, 14 had a
      temporary colostomy. Of these 14 patients, eight had a colostomy takedown and
      have maintained fecal continence. Of the 51 patients with ovarian cancer who had
      a low colorectal anastomosis, all achieved fecal continence. With the Miami
      Pouch, a urinary continence rate of 86% was obtained. Twenty-four (44%) patients
      had early complications, including ureteral obstruction, ureterocolonic
      anastomotic leak, reservoir cutaneous fistula, small bowel obstruction, and
      pyelonephritis. Nineteen (35%) patients had late complications, including
      ureteral reflux, urinary incontinence, difficult catheterizations, and reservoir
      stones. There was a perioperative mortality rate of 5%. CONCLUSIONS: Low
      colorectal anastomosis is an attractive alternative to permanent colostomy,
      allowing all patients who had the protective colostomies taken down to achieve
      fecal continence. Continent urinary diversion with the Miami Pouch is also a
      worthwhile procedure because of its high continence rate. Although survival
      advantage for either procedure has not been proven, the quality of life of
      patients undergoing such procedures has been substantially improved because of
      the avoidance of external appliances. This has been achieved with acceptable
      morbidity and mortality rates.

PMID- 9023842
TI  - Radiation palliation of cervical cancer.
AB  - Radiation is a useful modality for palliation of local-regional disease in
      patients with cervical cancer who require palliation because of distant
      metastases, extensive local-regional disease, medical consideration, or patient
      concerns. Two radiation schedules have been reported on for the treatment of
      advanced pelvic disease including cervical cancer. The large single-dose schedule
      consisted of 10-Gy fractions repeated at monthly intervals to a maximum of 30 Gy.
      This schedule has produced good palliative results with symptomatic improvement
      in approximately 50% of patients and objective response in 35%-80%. However,
      severe late toxicity was shown to be as high as 42% (actuarial). The second
      schedule tested by the Radiation Therapy Oncology Group consisted of 3.7-Gy
      fractions given twice a day for 2 days (14.8 Gy) repeated after 2-4 weeks for a
      maximum of 44.4 Gy. There were 284 patients accrued, and the subgroup of 61
      cervical cancer patients is analyzed in this article. The subjective response
      (50%-100% complete response) and objective response (53%) were similar to those
      observed with the large single-fraction schedule. The late toxicity was
      significantly lower (7%-actuarial). For patients who may survive 6 months or
      longer, this second schedule is preferable.

PMID- 9023843
TI  - New directions for radiation biology research in cancer of the uterine cervix.
AB  - A simplified model for tumorigenesis, locoregional growth, and metastases is
      proposed for carcinoma of the cervix. With the use of this model, four potential
      areas for future directions for radiobiologic-clinical research are identified.
      The first area concerns the influence of human papillomavirus infection and p53
      mutations on tumor biology, with particular reference to radiosensitivity and
      metastatic potential. Research in this area should be most fruitful. The second
      area focuses on the influence of hypoxia on clinical outcome in carcinoma of the
      cervix. The use of selective hypoxic cell toxins (e.g., tirapazamine) for phase
      II testing in hypoxic tumors is recommended. The third area concerns the
      development and clinical confirmation of assays for the prediction of intrinsic
      tumor radiosensitivity (e.g., surviving fraction after 2 Gy) and normal tissue
      radiosensitivity. The need exists for more rapid assays so that their results can
      be available prior to institution of therapy. The influence of the intrinsic
      radiosensitivity of normal tissues (especially in patients who are heterozygotes
      for ataxia-telangiectasia and patients with autoimmune disease) may permit
      identification of those at increased risk for complications so that alternative,
      less toxic treatment can be allocated. The fourth area for additional study
      concerns the influence of both intrinsic (c-myc amplification, matrix
      metalloproteinase levels) and extrinsic factors (fever, immunosuppression) on the
      development of distant metastases. Such investigations will permit identification
      of patients at high risk of developing distant metastases so that adjuvant
      treatments (e.g., chemotherapy or metalloproteinase inhibitors) can be explored.
      It is believed that future clarification of our proposed model will lead to other
      worthwhile areas for therapeutic intervention.

PMID- 9023844
TI  - Human papillomavirus biology.

PMID- 9023845
TI  - Human papillomavirus immunology and vaccine prospects.
AB  - As a result of several recent advances in molecular biology, the association
      between human papillomavirus (HPV) infection and cervical cancer has been firmly
      established and the oncogenic potential of certain HPV types has been clearly
      demonstrated. These observations provide the impetus for the development of novel
      vaccines to prevent or treat HPV-associated cervical cancer. Because there is no
      effective culturing system to propagate HPV, traditional approaches for studying
      HPV and developing vaccines have been hampered. However, recent studies using
      recombinant subunit preparations in animals have yielded promising results and
      encourage their investigation in human trials. Strategies currently under
      investigation focus on the induction of effective humoral immune responses for
      prophylaxis against subsequent HPV infection; for the treatment of existing HPV
      infections, techniques to improve cell-mediated immunity by enhancing viral
      antigen recognition are being studied. Small-scale human trials using several
      different vaccine approaches should be completed within the next few years and
      field trials of the most promising one(s) could begin within a decade. The
      development of successful therapeutic and/or prophylactic vaccines offers an
      attractive alternative to existing screening and treatment programs for cervical
      cancer and may result in a substantial reduction in the worldwide morbidity from
      this disease.

PMID- 9023865
TI  - The thoracic inlet: normal anatomy.
AB  - The thoracic inlet is the junction between the neck and the chest. A number of
      neural structures traverse this region. A knowledge of the location of these
      various neural structures and their relationship to one another is important when
      interpreting cross-sectional images of this region. This article will review the
      normal anatomy of the major neural structures that are found in this region.

PMID- 9023866
TI  - The brachial plexus.
AB  - The brachial plexus arises from the lower cervical and upper thoracic spinal
      nerve roots. It courses between the anterior and middle scalene muscles and
      adjacent to the subclavian artery. The brachial plexus may be visualized by both
      MRI and CT. Symptoms of a brachial plexopathy commonly are nonlocalizing.
      Traumatic injuries and involvement by tumors probably account for the majority of
      etiologies responsible for these plexopathies. Inflammatory processes also
      involve the brachial plexus. This article reviews the anatomy of the brachial
      plexus from both surgical and radiographic approaches and also addresses the
      symptomatology of brachial plexopathy underlying it.

PMID- 9023867
TI  - Imaging of the thyroid gland.
AB  - The thyroid gland is critical in regulating metabolic functions including cardiac
      rate and output, lipid catabolism, skeletal growth, and oxygen and heat
      production. Thus, patients with hormonally active thyroid abnormalities present
      with wide-ranging symptoms, requiring an understanding of the gland's hormonal
      functions. Radiological imaging assesses the pathophysiological affects of
      abnormal thyroid function as well as important morphological features. Nuclear
      scintigraphy provides functional information about the gland, whereas cross
      sectional imaging-including ultrasound, CT, and MR-provide adjunctive anatomic
      information. These modalities also provide information about related structures
      in the neck. The embryology, anatomy, and physiology of the thyroid are
      discussed; congenital, autoimmune, inflammatory, metabolic, and neoplastic
      diseases are reviewed; and the diagnostic utility of radiological imaging is
      addressed.

PMID- 9023868
TI  - Imaging of the parathyroid glands.
AB  - Primary hyperparathyroidism resulting in hypercalcemia is the most common
      presentation of parathyroid pathology and usually is related to a parathyroid
      adenoma and, less commonly, to hyperplasia. Imaging of the parathyroid glands
      focuses on the detection of adenomas in patients with primary
      hyperparathyroidism. The role of imaging (as well as the modality used) for
      preoperative localization of the parathyroid glands continues to be
      controversial. The embryology, anatomy, and physiology of the parathyroid glands
      are reviewed. The diagnostic utility of radiological imaging-including
      ultrasonography, CT, MR imaging, and nuclear scintigraphy-are discussed,
      particularly as it pertains to the evaluation of primary hyperparathyroidism.

PMID- 9023869
TI  - Lesions and nodes of the thoracic inlet.
AB  - The anatomy of the thoracic inlet and lesions of the thyroid gland, parathyroid
      glands, and brachial plexus are discussed in depth in other articles in this
      issue. The focus of this article is to review lesions of the remaining structures
      and spaces that abut or traverse through the plane of the thoracic inlet.
      Although this junction of the neck with the chest is relatively easy to define on
      coronal or sagittal MR, determining this level with axial CT and MR is actually a
      bit of a challenge. Depending on neck length, degree of neck extension, shoulder
      thickness, arm position, thoracic kyphosis, and scan angle, the appearance of
      this area is extremely variable. For the purpose of this article, the thoracic
      inlet is better regarded as a zone or volume extending several centimeters both
      above and below this plane. In addition, this zone is very prone to CT beam
      hardening artifacts from the thickness of the shoulders as well as MR pulsation,
      respiratory, and bulk susceptibility artifacts, often resulting in less than
      esthetic images.

PMID- 9023870
TI  - Crete, channels, cells, circuits and computers.

PMID- 9023871
TI  - Motor imagery: never in your wildest dream.

PMID- 9023872
TI  - How should brain nuclei be delineated? Consequences for developmental mechanisms
      and for correlations of area size, neuron numbers and functions of brain nuclei.
AB  - The measurement of the size of brain areas and their neuron numbers depends on
      the delineation of the boundaries of a brain area. The comparison of
      cytoarchitectural, cytochemical and connectional delineation of a brain area,
      such as the vocal control nucleus HVC (nucleus hyperstriatalis ventralis, pars
      caudalis) of songbirds, shows that the estimated size of a nucleus depends on the
      delineation criterion. In correlation, the cytoarchitectural, cytochemical and
      projection properties of the same brain area change independently both during
      development and in adulthood. This needs to be considered in cross-species,
      intersexual, developmental and temporal comparisons of brain areas. The
      combination of cytoarchitectural criteria with area-specific cytochemical and
      connectional markers to delineate the boundaries of a brain nucleus gives new
      insights into neural plasticity and parcelation of brain areas.

PMID- 9023873
TI  - Beta-interferon and multiple sclerosis.
AB  - Interferon-beta (IFN-beta) is the first therapeutic intervention shown to alter
      the natural history of multiple sclerosis (MS), a relapsing then progressive
      inflammatory degenerative disease of the CNS. Since publication of the first
      randomized placebo-controlled trial of IFN-beta, and subsequent acquisition of US
      and European product licences for use in relapsing-remitting MS, the hopes and
      expectations of patients have been elevated greatly only to be dampened as more
      critical analysis of the trial results, in conjunction with the cost of
      treatment, led to marked limitations on prescription in several countries. IFN
      beta is not a cure. Here we review what is known about the mechanisms of action
      of IFN-beta in demyelinating disease, and propose a possible model of action of
      IFN-beta in the treatment of MS.

PMID- 9023874
TI  - Ionic effects of the Alzheimer's disease beta-amyloid precursor protein and its
      metabolic fragments.
AB  - Alzheimer's disease is a progressive dementia characterized in part by deposition
      of proteinaceous plaques in various areas of the brain. The main plaque protein
      component is beta-amyloid, a metabolic product of the beta-amyloid precursor
      protein. Substantial evidence has implicated beta-amyloid (and other
      amyloidogenic fragments of the precursor protein) with the neurodegeneration
      observed in Alzheimer's disease. Recently, beta-amyloid precursor protein and its
      amyloidogenic metabolic fragments have been shown to alter cellular ionic
      activity, either through interaction with existing channels or by de novo channel
      formation. Such alteration in ionic homeostasis has also been linked with
      cellular toxicity and might provide a molecular mechanism underlying the
      neurodegeneration seen in Alzheimer's disease.

PMID- 9023875
TI  - Sensorimotor stimulation to improve locomotor recovery after spinal cord injury.
AB  - Functional recovery after CNS injury may depend, in part, upon reorganization of
      undamaged neural pathways. Spinal cord circuits are capable of significant
      reorganization, in the form of both activity-dependent and injury-induced
      plasticity. This plasticity is manifest behaviourally in the ability of spinal
      animals to learn new locomotor tasks. Recent work with spinal-injured humans
      demonstrates that training can improve functional locomotor abilities. New
      methodologies to enhance limb movement are designed to exploit further the
      plastic capabilities of the spinal cord by reinforcing appropriate connections in
      an activity-dependent manner. In the future, these methods might also prove
      useful in guiding and strengthening functional synaptogenesis of regenerating
      axons to maximize their contribution towards restoration of function.

PMID- 9023876
TI  - Neurocircuitry of stress: central control of the hypothalamo-pituitary
      adrenocortical axis.
AB  - Integration of the hypothalamo-pituitary-adrenal stress response occurs by way of
      interactions between stress-sensitive brain circuitry and neuroendocrine neurons
      of the hypothalamic paraventricular nucleus (PVN). Stressors involving an
      immediate physiologic threat ('systemic' stressors) are relayed directly to the
      PVN, probably via brainstem catecholaminergic projections. By contrast, stressors
      requiring interpretation by higher brain structures ('processive' stressors)
      appear to be channeled through limbic forebrain circuits. Forebrain limbic sites
      connect with the PVN via interactions with GABA-containing neurons in the bed
      nucleus of the stria terminalis, preoptic area and hypothalamus. Thus, final
      elaboration of processive stress responses is likely to involve modulation of PVN
      GABAergic tone. The functional and neuroanatomical data obtained suggest that
      disease processes involving inappropriate stress control involve dysfunction of
      processive stress pathways.

PMID- 9023877
TI  - GAP-43: an intrinsic determinant of neuronal development and plasticity.
AB  - Several lines of investigation have helped clarify the role of GAP-43 (FI, B-50
      or neuromodulin) in regulating the growth state of axon terminals. In transgenic
      mice, overexpression of GAP-43 leads to the spontaneous formation of new synapses
      and enhanced sprouting after injury. Null mutation of the GAP-43 gene disrupts
      axonal pathfinding and is generally lethal shortly after birth. Manipulations of
      GAP-43 expression likewise have profound effects on neurite outgrowth for cells
      in culture. GAP-43 appears to be involved in transducing intra- and extracellular
      signals to regulate cytoskeletal organization in the nerve ending.
      Phosphorylation by protein kinase C is particularly significant in this regard,
      and is linked with both nerve-terminal sprouting and long-term potentiation. In
      the brains of humans and other primates, high levels of GAP-43 persist in
      neocortical association areas and in the limbic system throughout life, where the
      protein might play an important role in mediating experience-dependent
      plasticity.

PMID- 9023903
TI  - Government issues draft legislation on welfare during transport.

PMID- 9023878
TI  - Presynaptic nicotinic ACh receptors.
AB  - Nicotinic ACh (nACh) receptors in the CNS are composed of a diverse array of
      subunits and have a range of pharmacological properties. However, despite the
      fact that they are ligand-gated cation channels, their physiological functions
      have not been determined. This has led to increased interest in presynaptic nACh
      receptors that act to modulate the release of transmitter from presynaptic
      terminals.

PMID- 9023904
TI  - Effectiveness of SAG1 oral vaccine for the long-term protection of red foxes
      (Vulpes vulpes) against rabies.
AB  - Three groups of 10 foxes were vaccinated by the direct oral instillation of 2 ml
      of SAG1 rabies virus vaccine containing 10(6) MICLD50 (10(7) TCID50/ml)
      infectious viral particles/ml. SAG1 is a natural variant of the attenuated rabies
      vaccine strain SAD Bern and was selected in the presence of monoclonal
      antibodies. The strain is devoid of residual pathogenicity for the fox and the
      highly susceptible adult laboratory mouse by the oral, intramuscular and
      intracerebral routes. The foxes were challenged six, 12 and 18 months later with
      a virulent vulpine street rabies virus (GS 7-1-1). They all survived, whereas
      seven of eight unvaccinated control foxes died.

PMID- 9023905
TI  - Association between natural scrapie and PrP genotype in a flock of Suffolk sheep
      in Scotland.
AB  - The incidence of natural scrapie in sheep is associated with polymorphisms of the
      PrP gene, particularly those at codons 136, 154 and 171. In many breeds, the PrP
      allele encoding valine at codon 136 confers an extremely high risk of scrapie,
      but in Suffolk sheep this allele is vanishingly rare. In this study of a single
      closed flock of Suffolk sheep in Scotland, scrapie occurred primarily in animals
      which were homozygous for glutamine at codon 171, a genotype which was
      significantly less frequent in healthy flockmates. However, the apparent linkage
      between glutamine at codon 171 and scrapie was not completely recessive because
      two of 64 scrapie cases were heterozygous glutamine/arginine. These results
      suggest that breeding for increased resistance to scrapie in Suffolks by the
      selection of animals according to their PrP genotype is a feasible option.

PMID- 9023906
TI  - Persistence of the efficacy of pour-on and injectable moxidectin against
      Ostertagia ostertagi and Dictyocaulus viviparus in experimentally infected
      cattle.
AB  - The persistence of the efficacy of moxidectin 0.5 per cent pour-on and moxidectin
      1 per cent injectable against Ostertagia ostertagi and Dictyocaulus viviparus in
      calves was studied in two experimental trials. In the first trial two groups of
      seven calves were treated with either the pour-on or the injectable formulation,
      while a third group remained untreated. All the animals were infected daily from
      Monday to Friday with infective stages of O ostertagi and D viviparus between the
      day of treatment (day 0) and day 33, and were necropsied for worm counts three
      days later. The experimental design of the second trial was similar to that of
      the first but the period of infection was from 28 to 45 days after the treatment,
      and the necropsy was five days after the last infection. In both trials both
      moxidectin formulations had very high efficacies (99.6 per cent) against adult
      and developing stages of O ostertagi and D viviparus. The higher efficacy of the
      moxidectin pour-on preparation against early fourth stage larvae in both trials
      suggested that its effect was more persistent. It was calculated that the
      efficacy of moxidectin against O ostertagi persisted for at least five weeks for
      the injectable formulation and six weeks for the pour-on. The efficacy of
      moxidectin against D viviparus lasted for at least six weeks for both
      formulations.

PMID- 9023908
TI  - Surgical removal of a fibropapilloma from the reticulum causing apparent vagal
      indigestion.

PMID- 9023907
TI  - A new type of intraocular prosthesis for dogs.
AB  - A simple technique is described in which sterile silicone oil (viscosity 350 cSt)
      was injected into the globe of an eviscerated eye with an intact cornea and
      sclera; the volume injected was calculated from the formula 3/4 pi r3 where 'r'
      was the horizontal corneal diameter. After induction of general anaesthesia and
      routine preparation of the surgical site, the globe was eviscerated by using a
      transscleral or transcorneal approach. The procedure was carried out in five dogs
      with follow-ups ranging between 19 and 27 months. None of the eyes developed
      postoperative complications. In one dog, more silicone oil had to be injected 10
      days after surgery to increase the size of the globe to match the other eye. The
      intraocular contents were removed more easily by using the transcorneal approach,
      which also resulted in a perfect adjustment and virtually eliminated the
      possibility of leakage of silicone oil, than by a transscleral approach. The dogs
      responded extremely well and their owners were satisfied with the cosmetic
      appearance of their pets.

PMID- 9023909
TI  - Electron microscopic demonstration of an adenovirus in the hepatocytes of birds
      experimentally infected with hydropericardium syndrome.

PMID- 9023910
TI  - Massive Filaroides hirthi infestation associated with canine distemper in a
      puppy.

PMID- 9023911
TI  - Salmonellosis associated with S typhimurium DT104 in the USA.

PMID- 9023912
TI  - S typhimurium DT104 in cattle in the UK.

PMID- 9023913
TI  - Treatment of horses in training.

PMID- 9023914
TI  - The 48-hour week.

PMID- 9023915
TI  - Travel sickness in cattle.

PMID- 9023916
TI  - Cloning of cellobiose phosphoenolpyruvate-dependent phosphotransferase genes:
      functional expression in recombinant Escherichia coli and identification of a
      putative binding region for disaccharides.
AB  - Genomic libraries from nine cellobiose-metabolizing bacteria were screened for
      cellobiose utilization. Positive clones were recovered from six libraries, all of
      which encode phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS)
      proteins. Clones from Bacillus subtilis, Butyrivibrio fibrisolvens, and
      Klebsiella oxytoca allowed the growth of recombinant Escherichia coli in
      cellobiose-M9 minimal medium. The K. oxytoca clone, pLOI1906, exhibited an
      unusually broad substrate range (cellobiose, arbutin, salicin, and
      methylumbelliferyl derivatives of glucose, cellobiose, mannose, and xylose) and
      was sequenced. The insert in this plasmid encoded the carboxy-terminal region of
      a putative regulatory protein, cellobiose permease (single polypeptide), and
      phospho-beta-glucosidase, which appear to form an operon (casRAB). Subclones
      allowed both casA and casB to be expressed independently, as evidenced by in
      vitro complementation. An analysis of the translated sequences from the EIIC
      domains of cellobiose, aryl-beta-glucoside, and other disaccharide permeases
      allowed the identification of a 50-amino-acid conserved region. A disaccharide
      consensus sequence is proposed for the most conserved segment (13 amino acids),
      which may represent part of the EIIC active site for binding and phosphorylation.

PMID- 9023918
TI  - Purification and characterization of two bifunctional chitinases/lysozymes
      extracellularly produced by Pseudomonas aeruginosa K-187 in a shrimp and crab
      shell powder medium.
AB  - Two extracellular chitinases (FI and FII) were purified from the culture
      supernatant of Pseudomonas aeruginosa K-187. The molecular weights of FI and FII
      were 30,000 and 32,000, respectively, by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and 60,000 and 30,000, respectively, by gel filtration. The
      pIs for FI and FII were 5.2 and 4.8, respectively. The optimum pH, optimum
      temperature, pH stability, and thermal stability of FI were pH 8, 50 degrees C,
      pH 6 to 9, and 50 degrees C; those of FII were pH 7, 40 degrees C, pH 5 to 10,
      and 60 degrees C. The activities of both enzymes were activated by Cu2+; strongly
      inhibited by Mn2+, Mg2+, and Zn2+; and completely inhibited by glutathione,
      dithiothreitol, and 2-mercaptoethanol. Both chitinases showed lysozyme activity.
      The purified enzymes had antibacterial and cell lysis activities with many kinds
      of bacteria. This is the first report of a bifunctional chitinase/lysozyme from a
      prokaryote.

PMID- 9023917
TI  - Construction and use of a versatile set of broad-host-range cloning and
      expression vectors based on the RK2 replicon.
AB  - The plasmid vectors described in this report are derived from the broad-host
      range RK2 replicon and can be maintained in many gram-negative bacterial species.
      The complete nucleotide sequences of all of the cloning and expression vectors
      are known. Important characteristics of the cloning vectors are as follows: a
      size range of 4.8 to 7.1 kb, unique cloning sites, different antibiotic
      resistance markers for selection of plasmid-containing cells, oriT-mediated
      conjugative plasmid transfer, plasmid stabilization functions, and a means for a
      simple method for modification of plasmid copy number. Expression vectors were
      constructed by insertion of the inducible Pu or Pm promoter together with its
      regulatory gene xylR or xylS, respectively, from the TOL plasmid of Pseudomonas
      putida. One of these vectors was used in an analysis of the correlation between
      phosphoglucomutase activity and amylose accumulation in Escherichia coli. The
      experiments showed that amylose synthesis was only marginally affected by the
      level of basal expression from the Pm promoter of the Acetobacter xylinum
      phosphoglucomutase gene (celB). In contrast, amylose accumulation was strongly
      reduced when transcription from Pm was induced. CelB was also expressed with a
      very high induction ratio in Xanthomonas campestris. These experiments showed
      that the A. xylinum celB gene could not complement the role of the bifunctional
      X. campestris phosphoglucomutase-phosphomannomutase gene in xanthan biosynthesis.
      We believe that the vectors described here are useful for cloning experiments,
      gene expression, and physiological studies with a wide range of bacteria and
      presumably also for analysis of gene transfer in the environment.

PMID- 9023919
TI  - Bacteria, molds, and toxins in water-damaged building materials.
AB  - Microbial toxins and eukaryotic cell toxicity from indoor building materials
      heavily colonized by fungi and bacteria were analyzed. The dominant colonizers at
      water-damaged sites of the building were Stachybotrys chartarum (10(3) to 10(5)
      visible conidia cm-2), Penicillium and Aspergillus species (10(4) CFU mg-1), gram
      negative bacteria (10(4) CFU mg-1), and mycobacteria (10(3) CFU mg-1). The
      mycobacterial isolates were most similar to M. komossense, with 98% similarity of
      the complete 16S rDNA sequence. Limulus assay of water extracts prepared from a
      water-damaged gypsum liner revealed high contents of gram-negative endotoxin (17
      ng mg-1 of E. coli lipopolysaccharide equivalents) and beta-D-glucan (210 ng mg-1
      of curdlan equivalents). High-performance liquid chromatography analysis of the
      methanol extracts showed that the water-damaged gypsum liner also contained
      satratoxin (17 ng mg-1). This methanol-extracted substance was 200 times more
      toxic to rabbit skin and fetus feline lung cells than extract of gypsum liner
      sampled from a non-water-damaged site. The same extract contained toxin(s) that
      paralyzed the motility of boar spermatozoa at extremely low concentrations; the
      50% effective concentration was 0.3 microgram of dry solids per ml. This toxicity
      was not explainable by the amount of bacterial endotoxin, beta-D-glucan, or
      satratoxin present in the same extract. The novel in vitro toxicity test that
      utilized boar spermatozoa as described in this article is convenient to perform
      and reproducible and was a useful tool for detecting toxins of microbial origin
      toward eukaryotic cells not detectable in building materials by the other
      methods.

PMID- 9023921
TI  - An aminotransferase from Lactococcus lactis initiates conversion of amino acids
      to cheese flavor compounds.
AB  - The enzymatic degradation of amino acids in cheese is believed to generate aroma
      compounds and therefore to be involved in the complex process of cheese flavor
      development. In lactococci, transamination is the first step in the degradation
      of aromatic and branched-chain amino acids which are precursors of aroma
      compounds. Here, the major aromatic amino acid aminotransferase of a Lactococcus
      lactis subsp. cremoris strain was purified and characterized. The enzyme
      transaminates the aromatic amino acids, leucine, and methionine. It uses the
      ketoacids corresponding to these amino acids and alpha-ketoglutarate as amino
      group acceptors. In contrast to most bacterial aromatic aminotransferases, it
      does not act on aspartate and does not use oxaloacetate as second substrate. It
      is essential for the transformation of aromatic amino acids to flavor compounds.
      It is a pyridoxal 5'-phosphate-dependent enzyme and is composed of two identical
      subunits of 43.5 kDa. The activity of the enzyme is optimal between pH 6.5 and 8
      and between 35 and 45 degrees C, but it is still active under cheese-ripening
      conditions.

PMID- 9023920
TI  - Isolation and characterization of a bacteriocin (Butyrivibriocin AR10) from the
      ruminal anaerobe Butyrivibrio fibrisolvens AR10: evidence in support of the
      widespread occurrence of bacteriocin-like activity among ruminal isolates of B.
      fibrisolvens.
AB  - Forty-nine isolates of Butyrivibrio fibrisolvens and a single isolate of
      Butyrivibrio crossotus were screened for the production of inhibitors by a
      deferred plating procedure. Twenty-five isolates produced factors which, to
      various degrees, inhibited the growth of the other Butyrivibrio isolates. None of
      the inhibitory activity was due to bacteriophages. The inhibitory products from
      18 of the producing strains were sensitive to protease digestion. Differences in
      the ranges of activity among the Butyrivibrio isolates and protease sensitivity
      profiles suggest that a number of different inhibitory compounds are produced.
      These findings suggest that the production of bacteriocin-like inhibitors may be
      a widespread characteristic throughout the genus Butyrivibrio. The bacteriocin
      like activity from one isolate, B. fibrisolvens AR10, was purified and confirmed
      to reside in a single peptide. Crude bacteriocin extracts were prepared by
      ammonium sulfate and methanol precipitation of spent culture supernatants,
      followed by dialysis and high-speed centrifugation. The active component was
      isolated from the semicrude extract by reverse-phase chromatography. Tricine
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed that the
      peptide was purified to homogeneity, having an estimated molecular mass of
      approximately 4,000 Da. The N terminus of the peptide was blocked. A cyanogen
      bromide cleavage fragment of the native peptide yielded a sequence of 20 amino
      acids [(M)GIQLAPAXYQDIVNXVAAG]. No homology with previously reported bacteriocins
      was found. Butyrivibriocin AR10 represents the first bacteriocin isolated from a
      ruminal anaerobe.

PMID- 9023922
TI  - Use of rRNA gene restriction patterns to evaluate lactic acid bacterium
      contamination of vacuum-packaged sliced cooked whole-meat product in a meat
      processing plant.
AB  - Molecular typing was applied to an in-plant lactic acid bacterium (LAB)
      contamination analysis of a vacuum-packaged sliced cooked whole-meat product. A
      total of 982 LAB isolates from the raw mass, product, and the environment at
      different production stages were screened by restriction endonuclease (EcoRI and
      HindIII) analysis. rRNA gene restriction patterns were further determined for
      different strains obtained from each source. These patterns were used for
      recognizing the spoilage-causing LAB strains from the product on the sell-by day
      and tracing the sources and sites of spoilage LAB contamination during the
      manufacture. LAB typing resulted in 71 different ribotypes, of which 27 were
      associated with contamination routes. Raw material was distinguished as the
      source of the major spoilage strains. Contamination of the product surfaces after
      cooking was shown to be airborne. The removal of the product from the cooking
      forms was localized as a major site of airborne LAB contamination. Food handlers
      and some surfaces in contact with the product during the manufacture were also
      contaminated with the spoilage strains. Some LAB strains were also able to resist
      cooking in the core of the product bar. These strains may have an effect on the
      product shelf life by contaminating the slicing machine. The air in the slicing
      department and adjacent cold room contained very few LAB. Surface-mediated
      contamination was detected during the slicing and packaging stages. Food handlers
      also carried strains later found in the packaged product. Molecular typing
      provided useful information revealing the LAB contamination sources and sites of
      this product. The production line will be reorganized in accordance with these
      results to reduce spoilage LAB contamination.

PMID- 9023923
TI  - Cloning of genes coding for L-sorbose and L-sorbosone dehydrogenases from
      Gluconobacter oxydans and microbial production of 2-keto-L-gulonate, a precursor
      of L-ascorbic acid, in a recombinant G. oxydans strain.
AB  - We have purified L-sorbose dehydrogenase (SDH) and L-sorbosone dehydrogenase
      (SNDH) from Gluconobacter oxydans T-100 that showed an ability to convert D
      sorbitol to 2-keto-L-gulonate (2-KLGA). A genomic library of Gluconobacter
      oxydans T-100 was screened with a probe, a 180-bp PCR product which was obtained
      from degenerate oligodeoxyribonucleotides based on the elucidated sequence of the
      purified SDH (used as primers) and the genomic DNA of G. oxydans T-100 (used as a
      template). From sequencing of the DNA from a clone positive to the probe, the
      SNDH and the SDH were estimated to be coded in sequential open reading frames
      with 1,497 and 1,599 nucleotides, respectively, which was confirmed by expression
      of the DNA in Escherichia coli that showed both enzymatic activities. The DNA was
      introduced to a shuttle vector which was prepared from a plasmid of G. oxydans T
      100 and pHSG298 to obtain an expression vector designated pSDH155. The production
      of 2-KLGA by pSDH155 in G. oxydans G624, an L-sorbose-accumulating strain, was
      improved to 230% compared to that of G. oxydans T-100. Chemical mutation of the
      host strain to suppress the L-idonate pathway and replacement of the original
      promoter with that of E. coli tufB resulted in improving the production of 2
      KLGA. Consequently, high-level production from D-sorbitol to 2-KLGA (130 mg/ml)
      was achieved by simple fermentation of the recombinant Gluconobacter.

PMID- 9023924
TI  - Acid adaptation sensitizes Salmonella typhimurium to hypochlorous acid.
AB  - Acid adaptation of Salmonella typhimurium at a pH of 5.0 to 5.8 for one to two
      cell doublings resulted in marked sensitization of the pathogen to halogen-based
      sanitizers including chlorine (hypochlorous acid) and iodine. Acid-adapted S.
      typhimurium was more resistant to an anionic acid sanitizer than was its
      nonadapted counterpart. A nonselective plating medium of tryptose phosphate agar
      plus 1% pyruvate was used throughout the study to help recover chemically
      stressed cells. Mechanisms of HOCl-mediated inactivation of acid-adapted and
      nonadapted salmonellae were investigated. Hypochlorous acid oxidized a higher
      percentage of cell surface sulfhydryl groups in acid-adapted cells than in
      nonadapted cells, and sulfhydryl oxidation was correlated with cell inactivation.
      HOCl caused severe metabolic disruptions in acid-adapted and nonadapted S.
      typhimurium, such as respiratory loss and inability to restore the adenylate
      energy charge from a nutrient-starved state. Sensitization of S. typhimurium to
      hypochlorous acid by acid adaptation also involved increased permeability of the
      cell surface because nonadapted cells treated with EDTA became sensitized. The
      results of this study establish that acid-adapted S. typhimurium cells are highly
      sensitized to HOCl oxidation and that inactivation by HOCl involves changes in
      membrane permeability, inability to maintain or restore energy charge, and
      probably oxidation of essential cellular components. This study provides a basis
      for improved practical technologies to inactivate Salmonella and implies that
      acid pretreatment of food plant environments may increase the efficacy of halogen
      sanitizers.

PMID- 9023926
TI  - Monoclonal antibodies for use in detection of Bacillus and Clostridium spores.
AB  - Five monoclonal antibodies against bacterial spores of Bacillus cereus T and
      Clostridium sporogenes PA3679 were developed. Two antibodies (B48 and B183) were
      selected for their reactivity with B. cereus T spores, two (C33 and C225) were
      selected for their reactivity with C. sporogenes spores, and one (D89) was
      selected for its reactivity with both B. cereus and C sporogenes spores. The
      isotypes of the antibodies were determined to be immunoglobulin G2a (IgG2a)
      (B48), IgG1 (B183), and IgM (C33, C225, and D89). The antibodies reacted with
      spores of B. cereus T, Bacillus subtilis subsp. globigii, Bacillus megaterium,
      Bacillus stearothermophilus, C. sporogenes, Clostridium perfringens, and
      Desulfotomaculum nigrificans. Antibody D89 also reacted with vegetative cells of
      B. cereus and C. sporogenes. Analysis of B. cereus spore extracts showed that two
      of the antigens with which the anti-Bacillus antibodies reacted had molecular
      masses of 76 kDa and approximately 250 kDa. Immunocytochemical localization
      indicated that antigens with which B48, B183, and D89 react are on the exosporium
      of the B. cereus T spore. Antibody D89 reacted with the exosporium and outer
      cortex of C. sporogenes spores in immunocytochemical localization studies but did
      not react with extracts of C. sporogenes or B. cereus spores in Western blotting.
      Some C. sporogenes antigens were not stable during long-term storage at -20
      degrees C. Antibodies B48, B183, and D89 should prove to be useful tools for
      developing immunological methods for the detection of bacterial spores.

PMID- 9023925
TI  - Identification of a gene for Cyt1A-like hemolysin from Bacillus thuringiensis
      subsp. medellin and expression in a crystal-negative B. thuringiensis strain.
AB  - A gene designated cyt1Ab1, encoding a 27,490-Da protein, was isolated from
      Bacillus thuringiensis subsp. medellin (H30 serotype) by using an oligonucleotide
      probe corresponding to the cyt1Aa1 gene. The sequence of the Cyt1Ab1 protein, as
      deduced from the sequence of the cyt1Ab1 gene, was 86% identical to that of the
      Cyt1Aa1 protein and 32% identical to that of the Cyt2Aa1 protein from B.
      thuringiensis subsp. kyushuensis. The cyt1Ab1 gene was flanked upstream by a p21
      gene, in the same orientation, encoding a 21,370-Da protein that showed 84%
      similarity to the putative chaperone P20 protein from B. thuringiensis subsp.
      israelensis and downstream, on the opposite strand, by a sequence showing 85%
      identity to the IS240A insertion sequence. The cyt1Ab1 gene was expressed at a
      high level in a nontoxic strain of B. thuringiensis subsp. israelensis in which
      large inclusions of the Cyt1Ab1 protein were produced. Purified Cyt1Ab1 crystals
      were as hemolytic as those of the Cyt1Aa1 protein and were twice as hemolytic as
      those from the wild-type strain. Mosquitocidal activity toward Aedes aegypti,
      Anopheles stephensi, and Culex pipiens larvae was assayed. The toxicity of the
      Cyt1Ab1 protein was slightly lower than that of the Cyt1Aa1 protein for all three
      mosquito species, and Cyt1Ab1 was 150, 300, and 800 times less active toward
      Culex, Anopheles, and Aedes larvae, respectively, than were the native crystals
      from B. thuringiensis subsp. medellin.

PMID- 9023927
TI  - Glucoamylase gene fusions alleviate limitations for protein production in
      Aspergillus awamori at the transcriptional and (post) translational levels.
AB  - In this study we have analyzed the effects of a glucoamylase gene fusion on the
      mRNA levels and protein levels for the human interleukin-6 gene (hil6) and the
      guar alpha-galactosidase gene (aglA). Previously it was shown that production of
      nonfused alpha-galactosidase and hIL-6 in Aspergillus awamori was limited at
      transcriptional and (post)translational levels, respectively (R. J. Gouka, P. J.
      Punt, J. G. M. Hessing, and C. A. M. J. J. van den Hondel, Appl. Environ.
      Microbiol. 62:1951-1957, 1996). Vectors were constructed which contained either
      the hil6 or aglA gene fused to the Aspergillus niger glucoamylase gene (glaA)
      under control of the efficient 1,4-beta-endoxylanase A promoter and transcription
      terminator. For comparison, the vectors were integrated in a single copy at the
      pyrG locus of A. awamori. A glaA fusion to the 5' end of the hil6 gene resulted
      in a large increase in hIL-6 yield, whereas with a glaA fusion to the 3' end of
      the hil6 gene, almost no protein was produced. Nevertheless, the steady-state
      mRNA levels of both fusions were very similar and not clearly increased compared
      to those of a strain expressing nonfused hIL-6. Fusions of glaA to the 5' end of
      the wild-type guar aglA gene resulted in truncated mRNA lacking almost 900 bases
      (> 80%) of the aglA sequence. When the coding sequence of the wild-type aglA gene
      was replaced by a synthetic aglA gene with optimized Saccharomyces cerevisiae
      codon usage, full-length mRNA was obtained. Compared to a nonfused synthetic aglA
      gene, a glaA fusion with the synthetic aglA gene resulted in a 25-fold increase
      in the mRNA level and, as a consequence, a similar increase in the alpha
      galactosidase protein level. The truncated transcripts derived from the wild-type
      aglA gene were further analyzed by nuclear run-on transcription assays. These
      experiments indicated that transcription elongation in the nucleus proceeded at
      least 400 bases downstream of the site where the truncation was determined,
      indicating that transcription elongation or premature termination was not the
      reason for the generation of truncated mRNAs. As the truncated mRNA also
      contained a poly(A) tail, truncation most likely occurs by incorrect processing
      of the aglA mRNA in the nucleus.

PMID- 9023928
TI  - Assessment of genetic diversity among strains of Pseudomonas syringae by PCR
      restriction fragment length polymorphism analysis of rRNA operons with special
      emphasis on P. syringae pv. tomato.
AB  - Phylogenetic relationships among 77 bacterial strains belonging to Pseudomonas
      syringae and Pseudomonas viridiflava species were assessed by analysis of the PCR
      restriction fragment length polymorphism (RFLP) patterns of three DNA fragments
      corresponding to rrs and rrl genes and the internal transcribed spacer, ITS1. No
      difference among all strains in rrs and rrl genes was observed with 14
      restriction enzymes, which confirms the close relationships existing between
      these two species. The nucleotidic sequence of the internal transcripted spacer
      (ITS1) between rrs and rrl for the P. syringae pv. syringae strain CFBP1392 was
      determined. Restriction maps of the PCR-amplified ITS1 region were prepared and
      compared for all 77 strains. Seventeen RFLP patterns, forming three main
      clusters, were distinguished. One contained all strains of P. syringae pv. tomato
      and of other pathovars which had been previously described as closely related by
      either pathogenicity studies or biochemical analyses. This cluster was equally
      far from P. viridiflava and from other P. syringae pathovars. These other
      pathovars of P. syringae formed a less coherent taxon.

PMID- 9023929
TI  - Proteinaceous factor(s) in culture supernatant fluids of bifidobacteria which
      prevents the binding of enterotoxigenic Escherichia coli to
      gangliotetraosylceramide.
AB  - We have examined the competitive binding of several species of Bifidobacterium
      and Escherichia coli Pb176, an enterotoxigenic E. coli (ETEC) strain, to
      gangliotetraosylceramide (asialo GM1 or GA1), a common bacterium-binding
      structure, and identified a factor(s) in the Bifidobacterium culture supernatant
      fluid that inhibits the binding of E. coli Pb176 to GA1. The ETEC strain we used
      expresses colonization factor antigen (CFA) II, which consists of coli surface
      associated antigens CS1 and CS3. Competitive exclusion of ETEC from GA1 molecules
      by Bifidobacterium cells was found by an in vitro thin-layer chromatography
      overlay binding suppression assay. However, the ETEC cells were less effective in
      blocking the adherence of Bifidobacterium cells to GA1. These findings suggest
      that the two bacterial species recognize different binding sites on the GA1
      molecule and that the mechanism of competitive exclusion is not due to specific
      blockage of a common binding site on the molecule. The neutralized culture
      supernatant fluids of Bifidobacterium species, including that of Bifidobacterium
      longum SBT 2928 (BL2928), showed remarkable inhibition of the ETEC binding to
      GA1. Our results suggest that the binding inhibitor produced by BL2928 is a
      proteinaceous molecule(s) with a molecular weight around or over 100,000 and a
      neutral isoelectric point. The binding inhibitor produced by BL2928 and other
      Bifidobacterium species is estimated to contribute to their normal anti
      infectious activities by preventing the binding of pathogenic strains of E. coli
      to GA1 on the surface of the human intestinal mucosa.

PMID- 9023930
TI  - Antagonistic activity exerted in vitro and in vivo by Lactobacillus casei (strain
      GG) against Salmonella typhimurium C5 infection.
AB  - The aim of this study was to compare the antagonistic properties of Lactobacillus
      casei GG exerted in vitro against Salmonella typhimurium C5 in a cellular model,
      cultured enterocyte-like Caco-2 cells, to those exerted in vivo in an animal
      model, C3H/He/Oujco mice. Our results show that a 1-h contact between the
      invading strain C5 and either the culture or the supernatant of L. casei GG
      impeded the invasion by the Salmonella strain in Caco-2 cells, without modifying
      the viability of the strain. After neutralization at pH 7, no inhibition of the
      invasion by C5 was observed. The antagonistic activity of L. casei GG was
      examined in C3H/He/Oujco mice orally infected with C5 as follows: (i) L. casei GG
      was given daily to conventional animals as a probiotic, and (ii) it was given
      once to germ-free animals in order to study the effect of the population of L.
      casei GG established in the different segments of the gut. In vivo experiments
      show that after a single challenge with C5, this strain survives and persists at
      a higher level in the feces of the untreated conventional mice than in those of
      the treated group. In L. casei GG germ-free mice, establishment of L. casei GG in
      the gut significantly delayed the occurrence of 100% mortality of the animals (15
      days after C5 challenge versus 9 days in germ-free mice [P < 0.01]). Cecal
      colonization level and translocation rate of C5 to the mesenteric lymph nodes,
      spleen, and liver were significantly reduced during the first 2 days post-C5
      challenge, although the L. casei GG population level in the gut dramatically
      decreased in these animals.

PMID- 9023931
TI  - Molecular detection of an importation of type 3 wild poliovirus into Canada from
      The Netherlands in 1993.
AB  - During the fall and winter of 1992-1993 an outbreak of wild poliovirus type 3
      associated poliomyelitis involving 71 patients occurred in The Netherlands.
      Almost all of the individuals involved in the outbreak belonged to an orthodox
      religious denomination that prohibits vaccination. A surveillance was initiated
      to determine if there had been an importation of this same strain of wild
      poliovirus into a southern Alberta community with a similar religious
      affiliation. Viral culture of stool samples from consenting individuals in the
      community resulted in viral isolates which typed as poliovirus type 3. Sequencing
      of amplicons generated from both the 5' nontranslated region and the VP1/2A
      portion of the genomes from representative poliovirus isolates indicated a
      greater than 99% genetic similarity to the strain from The Netherlands. The
      results of this study show that the utilization of PCR-based diagnostics offers
      an important molecular tool for the concise and rapid surveillance of possible
      cases of wild poliovirus importation into communities with individuals at risk
      for infection.

PMID- 9023932
TI  - Functional characterization of pediocin PA-1 binding to liposomes in the absence
      of a protein receptor and its relationship to a predicted tertiary structure.
AB  - The physicochemical interaction of pediocin PA-1 with target membranes was
      characterized using lipid vesicles made from the total lipids extracted from
      Listeria monocytogenes. Pediocin PA-1 caused the time- and concentration
      dependent release of entrapped carboxyfluorescein (CF) from the vesicles. The
      pediocin-induced CF efflux rates were higher under acidic conditions than under
      neutral and alkaline conditions and were dependent on both pediocin and lipid
      concentrations. A binding isotherm constructed on the basis of the Langmuir
      isotherm gave an apparent binding constant of 1.4 x 10(7) M-1 at pH 6.0. The
      imposition of a transmembrane potential (inside negative) increased the CF efflux
      rate by 88%. Pediocin PA-1 also permeablized synthetic vesicles composed only of
      phosphatidylcholine. Sequence alignments and secondary-structure predictions for
      the N terminus of pediocin PA-1 and other class IIa bacteriocins predicted that
      pediocin PA-1 contained two beta-sheets maintained in a hairpin conformation
      stabilized by a disulfide bridge. The structural model also revealed patches of
      positively charged residues, consistent with the argument that electrostatic
      interactions play an important role in the binding of pediocin PA-1 to the lipid
      vesicles. This study demonstrates that pediocin PA-1 can function in the absence
      of a protein receptor and provides a structural model consistent with these
      results.

PMID- 9023933
TI  - The Bacillus thuringiensis vegetative insecticidal protein Vip3A lyses midgut
      epithelium cells of susceptible insects.
AB  - The Vip3A protein is a member of a newly discovered class of vegetative
      insecticidal proteins with activity against a broad spectrum of lepidopteran
      insects. Histopathological observations indicate that Vip3A ingestion by
      susceptible insects such as the black cutworm (Agrotis ipsilon) and fall armyworm
      (Spodoptera frugiperda) causes gut paralysis at concentrations as low as 4 ng/cm2
      of diet and complete lysis of gut epithelium cells resulting in larval death at
      concentrations above 40 ng/cm2. The European corn borer (Ostrinia nubilalis), a
      nonsusceptible insect, does not develop any pathology upon ingesting Vip3A. While
      proteolytic processing of the Vip3A protein by midgut fluids obtained from
      susceptible and nonsusceptible insects is comparable, in vivo immunolocalization
      studies show that Vip3a binding is restricted to gut cells of susceptible
      insects. Therefore, the insect host range for Vip3A seems to be determined by its
      ability to bind gut cells. These results indicate that midgut epithelium cells of
      susceptible insects are the primary target for the Vip3A insecticidal protein and
      that their subsequent lysis is the primary mechanism of lethality. Disruption of
      gut cells appears to be the strategy adopted by the most effective insecticidal
      proteins.

PMID- 9023934
TI  - An enzyme-linked immunosorbent assay for detection of Vibrio vulnificus biotype
      2: development and field studies.
AB  - Vibrio vulnificus biotype 2 is a primary eel pathogen which constitutes a
      lipopolysaccharide (LPS)-based homogeneous O serogroup within the species. In the
      present work, we have developed an enzyme-linked immunosorbent assay (ELISA)
      based on the specificity of LPS for the detection of this pathogen. The ELISA
      specificity was confirmed after testing 36 biotype 2 strains from laboratory
      cultures and environmental samples, 31 clinical and environmental biotype 1
      isolates, and several strains of Vibrio, Aeromonas, and Yersinia species,
      including the fish pathogens V. anguillarum, V. furnissii, A. hydrophila, and Y.
      ruckerii. The detection limits for biotype 2 cells were around 10(4) to 10(5)
      cells/well, and the immunoassay was also able to detect cells in the
      nonculturable state. Artificially infected eels and environmental samples were
      analyzed, and the immunodetection was confirmed by cultural methods (isolation on
      selective and nonselective media before and after broth enrichment). With this
      methodology, V. vulnificus biotype 2 was successfully detected in infected eels
      and asymptomatic carriers, which suggests that eels can act as a reservoir for
      this pathogen.

PMID- 9023935
TI  - Listeria monocytogenes Scott A transports glucose by high-affinity and low
      affinity glucose transport systems.
AB  - Listeria monocytogenes transported glucose by a high-affinity phosphoenolpyruvate
      dependent phosphotransferase system and a low-affinity proton motive force
      mediated system. The low-affinity system (Km = 2.9 mM) was inhibited by 2
      deoxyglucose and 6-deoxyglucose, whereas the high-affinity system (Km = 0.11 mM)
      was inhibited by 2-deoxyglucose and mannose but not 6-deoxyglucose. Cells and
      vesicles artificially energized with valinomycin transported glucose or 2
      deoxyglucose at rates greater than those of de-energized cells, indicating that a
      membrane potential could drive uptake by the low-affinity system.

PMID- 9023936
TI  - Changes in the size and composition of intracellular pools of nonesterified
      coenzyme A and coenzyme A thioesters in aerobic and facultatively anaerobic
      bacteria.
AB  - Intracellular levels of three coenzyme A (CoA) molecular species, i.e.,
      nonesterified CoA (CoASH), acetyl-CoA, and malonyl-CoA, in a variety of aerobic
      and facultatively anaerobic bacteria were analyzed by the acyl-CoA cycling method
      developed by us. It was demonstrated that there was an intrinsic difference
      between aerobes and facultative anaerobes in the changes in the size and
      composition of CoA pools. The CoA pools in the aerobic bacteria hardly changed
      and were significantly smaller than those of the facultatively anaerobic
      bacteria. On the other hand, in the facultatively anaerobic bacteria, the size
      and composition of the CoA pool drastically changed within minutes in response to
      the carbon and energy source provided. Acetyl-CoA was the major component of the
      CoA pool in the facultative anaerobes grown on sufficient glucose, although CoASH
      was dominant in the aerobes. Therefore, the acetyl-CoA/CoASH ratios in
      facultatively anaerobic bacteria were 10 times higher than those in aerobic
      bacteria. In Escherichia coli K-12 cells, the addition of reagents to inhibit the
      respiratory system led to a rapid decrease in the amount of acetyl-CoA with a
      concomitant increase in the amount of CoASH, whereas the addition of cerulenin, a
      specific inhibitor of fatty acid synthase, triggered the intracellular
      accumulation of malonyl-CoA. The acylation and deacylation of the three CoA
      molecular species coordinated with the energy-yielding systems and the
      restriction of the fatty acid-synthesizing system of cells. These data suggest
      that neither the accumulation of acetyl-CoA nor that of malonyl-CoA exerts
      negative feedback on pyruvate dehydrogenase and acetyl-CoA carboxylase,
      respectively.

PMID- 9023937
TI  - Fast and accurate identification of Xenorhabdus and Photorhabdus species by
      restriction analysis of PCR-amplified 16S rRNA genes.
AB  - Thirteen bacterial strains of Xenorhabdus and 14 strains of Photorhabdus
      originating from a wide range of geographical and nematode host sources were
      typed by analyzing 16S rRNA gene (rDNA) restriction patterns obtained after
      digestion of PCR-amplified 16S rDNAs. Eight tetrameric restriction endonucleases
      were examined. A total of 17 genotypes were identified, forming two heterogeneous
      main clusters after analysis by the unweighted pair-group method using arithmetic
      averages: group I included all Xenorhabdus species and strains, symbionts of
      Steinernema, whereas group II encompassed the Photorhabdus strains, symbionts of
      Heterorhabditis. To identify the four valid species of Xenorhabdus and
      unclassified strains and all the genotypes of Photorhabdus luminescens, three
      restriction enzymes are required: CfoI, AluI, and HaeIII. Our results, in
      substantial agreement with DNA-DNA pairing and 16S rDNA sequence data, indicate
      that amplified 16S rDNA restriction analysis is a simple and accurate tool for
      identifying entomopathogenic nematode bacterial symbionts.

PMID- 9023938
TI  - Molecular characterization of the gene encoding an 18-kilodalton small heat shock
      protein associated with the membrane of Leuconostoc oenos.
AB  - In Leuconostoc oenos, different stresses such as heat, ethanol, and acid shocks
      dramatically induce the expression of an 18-kDa small heat shock protein called
      Lo 18. The corresponding gene (hsp18) was cloned from a genomic library of L.
      oenos constructed in Escherichia coli. A 2.3-kb DNA fragment carrying the hsp18
      gene was sequenced. The hsp18 gene encodes a polypeptide of 148 amino acids with
      a calculated molecular mass of 16,938 Da. The Lo18 protein has a significant
      identity with small heat shock proteins of the alpha-crystallin family. The
      transcriptional start site was determined by primer extension. This experiment
      allowed us to identify the promoter region exhibiting high similarity to
      consensus promoter sequences of gram-positive bacteria, as well as E. coli.
      Northern blot analysis showed that hsp18 consists of a unique transcription unit
      of 0.6 kb. Moreover, hsp18 expression seemed to be controlled at the
      transcriptional level. This small heat shock protein was found to be peripherally
      associated with the membrane of L. oenos.

PMID- 9023939
TI  - Comparison of cell wall proteins of Saccharomyces cerevisiae as anchors for cell
      surface expression of heterologous proteins.
AB  - The carboxyl-terminal regions of five cell wall proteins (Cwp1p, Cwp2p, Ag alpha
      1p, Tip1p, and Flo1p) and three potential cell wall proteins (Sed1p, YCR89w, and
      Tir1p) all proved capable of immobilizing alpha-galactosidase in the cell wall of
      Saccharomyces cerevisiae. The fraction of the total amount of fusion protein that
      was localized to the cell wall varied depending on the anchor domain used. The
      highest proportion of cell wall incorporation was achieved with Cwp2p, Ag alpha
      1p, or Sed1p as an anchor. Although 80% of these fusion proteins were
      incorporated in the cell wall, the total production of alpha-galactosidase-Ag
      alpha 1p was sixfold lower than that of alpha-galactosidase-Cwp2p and eightfold
      lower than that of alpha-galactosidase-Sed1p. Differences in mRNA levels were not
      responsible for this discrepancy, nor was an intracellular accumulation of alpha
      galactosidase-Ag alpha 1p detectable. A lower translation efficiency of the alpha
      galactosidase-AG alpha 1 fusion construct is most likely to be responsible for
      the low level of protein production. alpha-Galactosidase immobilized by the
      carboxyl-terminal 67 amino acids of Cwp2p was most effective in the hydrolysis of
      the high-molecular-weight substrate guar gum from Cyamopsis tetragonoloba. This
      indicates that the use of a large anchoring domain does not necessarily result in
      a better exposure of the immobilized enzyme to the exterior of the yeast cell.

PMID- 9023940
TI  - Monocentric and polycentric anaerobic fungi produce structurally related
      cellulases and xylanases.
AB  - Cellulase and xylanase cDNAs were isolated from a cDNA library of the polycentric
      anaerobic fungus Orpinomyces sp. strain PC-2 constructed in Escherichia coli. The
      cellulase cDNA (celB) was 1.8 kb long with an open reading frame (ORF) coding for
      a polypeptide of 471 amino acids, and the xylanase cDNA (xynA) was 1.2 kb long
      with an ORF encoding a polypeptide of 362 amino acids. Single transcripts of 1.9
      kb for celB and 1.5 kb for xynA were detected in total RNA of Orpinomyces grown
      on Avicel. Genomic DNA regions coding for CelA and XynA were devoid of introns.
      The enzymes were highly homologous (80 to 85% identity) to the corresponding
      enzymes of the monocentric anaerobic fungus Neocallimastix patriciarum and, like
      those, contained in addition to a catalytic domain, a noncatalytic repeated
      peptide domain (NCRPD). The Orpinomyces xylanase contained one catalytic domain
      and thus differed from the Neocallimastix xylanase, which had two similar
      catalytic domains (H. J. Gilbert, G. P. Hazlewood, J. I. Lauie, C. G. Orpin, and
      G. P. Xue, Mol. Microbiol. 6:2065-2072, 1992). Two peptides corresponding to the
      catalytic domain and the NCRPD of XynA were synthesized, and antibodies against
      them were raised and affinity column purified. The antibodies against the
      catalytic domain peptide reacted specifically with the xylanases of Orpinomyces
      and Neocallimastix, while the antibodies against the NCRPD reacted with many (at
      least eight) extracellular proteins of Orpinomyces and Neocallimastix, suggesting
      that the NCRPD is present in a number of polypeptides.

PMID- 9023941
TI  - Aerobic and anaerobic metabolism of 6,10,14-trimethylpentadecan-2-one by a
      denitrifying bacterium isolated from marine sediments.
AB  - This report describes the metabolism of 6,10,14-trimethylpentadecan-2-one by a
      denitrifying bacterium (Marinobacter sp. strain CAB) isolated from marine
      sediments. Under aerobic and denitrifying conditions, this strain efficiently
      degraded this ubiquitous isoprenoid ketone. Several bacterial metabolites, 4,8,12
      trimethyl-tridecan-1-ol, 4,8,12-trimethyltridecanal, 4,8,12-trimethyltridecanoic
      acid, Z-3,7-dimethylocten-2-oic acid, Z-3,7,11-trimethyldodecen-2-oic acid, and
      6,10,14-trimethylpentadecan-2-ol, were formally identified, and different
      pathways were proposed to explain the formation of such isoprenoid compounds.

PMID- 9023942
TI  - Development and application of 16S rRNA-targeted probes for detection of iron-
      and manganese-oxidizing sheathed bacteria in environmental samples.
AB  - Comparative sequence analysis of the 16S rRNA genes from several Leptothrix and
      Sphaerotilus strains led to the design of an oligonucleotide probe (PS-1) based
      on a sequence within the hypervariable region 1 specific for four Leptothrix
      strains and for one of the four Sphaerotilus natans strains examined. Another
      probe (PSP-6) was based on a sequence within the hypervariable region 2. PSP-6
      was specific for one of the two evolutionary lineages previously described for
      Leptothrix spp. (P. L. Siering and W. C. Ghiorse, Int. J. Syst. Bacteriol. 46:173
      182, 1996). Fluorescein-labeled oligonucleotide probes were synthesized, and
      their specificity for fluorescence in situ hybridization identification was
      confirmed by a laser scanning microscopy technique (W. C. Ghiorse, D. N. Miller,
      R. L. Sandoli, and P. L. Siering, Microsc. Res. Tech. 33:73-86, 1996) to compare
      whole-cell hybridizations of closely related bacteria. Probe specificity was also
      tested in dot blot against total RNA isolated from four Leptothrix strains, four
      Sphaerotilus strains, and 15 other members of the class Proteobacteria. When the
      probes were tested on samples from the Sapsucker Woods wetland habitat where
      Leptothrix spp. are thought to play a role in manganese and iron oxidation,
      positive signals were obtained from several sheathed filamentous bacteria
      including some that were morphologically similar to previously isolated strains
      of "Leptothrix discophora." Other unknown filamentous sheathed bacteria also gave
      strong positive signals. This work provides a foundation for future studies
      correlating the presence of members of the Leptothrix-Sphaerotilus group of
      sheathed bacteria with manganese and iron oxidation activity in habitats where
      biological iron and manganese oxidation are important environmental processes.

PMID- 9023943
TI  - Identification and sequence analysis of two regulatory genes involved in
      anaerobic toluene metabolism by strain T1.
AB  - T1 is a denitrifying bacterium isolated for its ability to grow with toluene
      serving as the sole carbon source. Mutants of this strain that have defects in
      the toluene utilization pathway have been isolated and have been separated into
      classes based on growth phenotypes. A cosmid clone has been isolated by
      complementing the tutB16 (for toluene utilization) mutation. The complementing
      gene has been localized to a 3.3-kb DNA fragment. An additional open reading
      frame upstream of the tutB gene has also been identified and is designated tutC.
      The nucleotide sequence and the predicted amino acid translation of the 6.4-kb
      DNA fragment that contains these genes are presented. The tutB and tutC gene
      products of strain T1 have homology to members of the two-component sensor
      regulator family and are proposed to play a role in the regulation of toluene
      metabolic genes of strain T1. To our knowledge, this is the first published
      report of the isolation of mutants defective in anaerobic aromatic hydrocarbon
      degradation. Additionally, we report for the first time the cloning of genes
      involved in an anaerobic aromatic hydrocarbon degradation pathway.

PMID- 9023944
TI  - Cloning and sequence analysis of genes encoding xylanases and acetyl xylan
      esterase from Streptomyces thermoviolaceus OPC-520.
AB  - Three genes encoding two types of xylanases (STX-I and STX-II) and an acetyl
      xylan esterase (STX-III) from Streptomyces thermoviolaceus OPC-520 were cloned,
      and their DNA sequences were determined. The nucleotide sequences showed that
      genes stx-II and stx-III were clustered on the genome. The stx-I, stx-II, and stx
      III genes encoded deduced proteins of 51, 35.2, and 34.3 kDa, respectively. STX-I
      and STX-II bound to both insoluble xylan and crystalline cellulose (Avicel).
      Alignment of the deduced amino acid sequences encoded by stx-I, stx-II, and stx
      III demonstrated that the three enzymes contain two functional domains, a
      catalytic domain and a substrate-binding domain. The catalytic domains of STX-I
      and STX-II showed high sequence homology to several xylanases which belong to
      families F and G, respectively, and that of STX-III showed striking homology with
      an acetyl xylan esterase from S. lividans, nodulation proteins of Rhizobium sp.,
      and chitin deacetylase of Mucor rouxii. In the C-terminal region of STX-I, there
      were three reiterated amino acid sequences starting from C-L-D, and the repeats
      were homologous to those found in xylanase A from S. lividans, coagulation factor
      G subunit alpha from the horseshoe crab, Rarobacter faecitabidus protease I, beta
      1,3-glucanase from Oerskovia xanthineolytica, and the ricin B chain. However, the
      repeats did not show sequence similarity to any of the nine known families of
      cellulose-binding domains (CBDs). On the other hand, STX-II and STX-III contained
      identical family II CBDs in their C-terminal regions.

PMID- 9023945
TI  - Biochemical and mutational analysis of a gingipain-like peptidase activity from
      Prevotella ruminicola B(1)4 and its role in ammonia production by ruminal
      bacteria.
AB  - A chemical mutagenesis protocol was used with the ruminal bacterium Prevotella
      ruminicola strain B(1)4 to generate mutant strains defective in peptidase
      activity. Compared with the wild-type parent strain, the isolated mutants
      possessed 1/10 of the enzyme activity responsible for cleavage of glycine
      arginine-4-methoxy-beta-naphthylamide (Gly-Arg-MNA). A concomitant loss in
      activity against arginine-arginine-4-methoxy-beta-naphthylamide (Arg-Arg-MNA) was
      also observed. Both activities were similarly affected by various proteinase
      inhibitors, suggesting that the same enzyme is responsible for the Arg-Arg-MNA
      peptidase and Gly-Arg-MNA peptidase activities. Growth rates of wild-type and
      mutant strains grown in batch culture with various nitrogen sources did not
      differ. However, a role for the Gly-Arg-MNA peptidase activity was demonstrated
      in coculture experiments with gram-positive, ammonia-producing ruminal bacteria.
      The rate and extent of ammonia production were reduced by approximately 25% in
      cocultures containing the mutants when compared with that of wild-type-containing
      cultures. These reductions could not be accounted for simply by the decrease in
      ammonia production by the mutant strain alone. To our knowledge, this paper
      reports the first successful use of chemical mutagenesis with ruminal
      microorganisms.

PMID- 9023946
TI  - Transformation yields of chlorinated ethenes by a methanotrophic mixed culture
      expressing particulate methane monooxygenase.
AB  - Transformation yields for the aerobic cometabolic degradation of five chlorinated
      ethenes were determined by using a methanotrophic mixed culture expressing
      particulate methane monooxygenase (pMMO). Transformation yields (expressed as
      moles of chlorinated ethene degraded per mole of methane consumed) were 0.57,
      0.25, 0.058, 0.0019, and 0.00022 for trans-1,2-dichloroethylene (t-DCE), vinyl
      chloride (VC), cis-1,2-dichloroethylene (c-DCE), trichloroethylene (TCE), and 1,1
      dichloroethylene (1,1-DCE), respectively. Degradation of t-DCE and VC was
      observed only in the presence of formate or methane, sources of reducing energy
      necessary for cometabolism. The t-DCE and VC transformation yields represented 35
      and 15%, respectively, of the theoretical maximum yields, based on reducing
      energy availability from methane dissimilation to carbon dioxide, exclusive of
      all other processes that require reducing energy. The yields for t-DCE and VC
      were 20 times greater than the yields reported by others for cells expressing
      soluble methane monooxygenase (sMMO). Transformation yields for c-DCE, TCE, and
      1,1-DCE were similar to or less than those for cultures expressing sMMO. Although
      methanotrophic biotreatment systems have typically been designed to incorporate
      cultures expressing sMMO, these results suggest that pMMO expression may be
      highly advantageous for degradation of t-DCE or VC. It may also be much easier to
      maintain pMMO expression in treatment systems, because pMMO is expressed by all
      methanotrophs whereas sMMO is expressed only by type II methanotrophs under
      copper-limited conditions.

PMID- 9023947
TI  - The ldh phylogeny for environmental isolates of Lactococcus lactis is consistent
      with rRNA genotypes but not with phenotypes.
AB  - Lactate dehydrogenase (ldh) gene sequences, levels of 16S rRNA group-specific
      probe binding, and phenotypic characteristics were compared for 45 environmental
      isolates and four commercial starter strains of Lactococcus lactis to identify
      evolutionary groups best suited to cheddar cheese manufacture, ldh sequences from
      the environmental isolates showed high similarity to those from two groups of L.
      lactis used for industrial fermentations, L. lactis subsp. cremoris and subsp.
      lactis. Within each phylogenetically defined subspecies, ldh sequence
      similarities were greater than 99.1%. Strains with phenotypic traits formerly
      diagnostic for both subspecies were found in each ldh similarity group, but only
      strains belonging to L. lactis subsp. cremoris by both the newer, genetic and the
      older, superseded phenotypic criteria were judged potentially suitable for the
      commercial production of cheddar cheese. Identical evolutionary relationships
      were inferred from ldh sequences and from binding of subspecies-specific, 16S
      rRNA-directed oligonucleotide probes. However, groups defined according to these
      chromosomal traits bore no relationship to patterns of arginine deamination,
      carbon substrate utilization, or bacteriophage sensitivity, which may be encoded
      by cryptic genes or sexually transmissible genetic elements. Fourteen new L.
      lactis subsp. cremoris isolates were identified as suitable candidates for
      cheddar cheese manufacture, and 10 of these were completely resistant to three
      different batteries of commercial bacteriophages known to reduce starter
      activity.

PMID- 9023948
TI  - Detection system for Escherichia coli-specific virulence genes: absence of
      virulence determinants in B and C strains.
AB  - We describe a rational approach to simultaneously test Escherichia coli strains
      for the presence of known virulence genes in a reverse dot blot procedure.
      Specific segments of virulence genes of E. coli designed to have similar
      hybridization parameters were subcloned on plasmids and subsequently amplified by
      PCR as unlabeled probes in amounts sufficient to be bound to nylon membranes.
      Various pathogenic isolates and laboratory strains of E. coli were probed for the
      presence of virulence genes by labeling the genomic DNA of these strains with
      digoxigenin and then hybridizing them to the prepared nylon membranes. These
      hybridization results demonstrated that besides the E. coli K-12 safety strain
      derivatives, E. coli B and C strains are also devoid of genes encoding any of the
      investigated virulence factors. In contrast, pathogenic E. coli control strains,
      used to evaluate the method, showed typical hybridization patterns. The described
      probes and their easy application on a single filter were shown to provide a
      useful tool for the safety assessment of E. coli strains to be used as hosts in
      biotechnological processes. This approach might also be used for the
      identification and characterization of clinically significant E. coli isolates
      from human and animal species.

PMID- 9023949
TI  - Molecular evidence for association between the sphingobacterium-like organism
      "Candidatus comitans" and the myxobacterium Chondromyces crocatus.
AB  - Seven strains of the myxobacterium Chondromyces crocatus, isolated from widely
      separated geographic regions, were investigated for the presence of an associate
      gram-negative, rod-shaped companion bacterium that is phylogenetically related to
      the genus Sphingobacterium and has been named "Candidatus comitans" (C. A.
      Jacobi, E. Stackebrandt, H. Reichenbach, and B. J. Tindall, Int. J. Syst.
      Bacteriol. 46:119-122, 1996). Five of the Chondromyces strains were found to be
      associated with a companion bacterium, and one strain lost its companion during
      the study. A 16S ribosomal DNA (16S rDNA) clone library was generated for each
      Chondromyces culture. Sequence similarity was > 99.1% for all but one strain of
      C. crocatus and all but one strain of "Candidatus comitans". The three analyzed
      16S rDNA clone sequences of the companion of Cm c7 indicated that this companion
      strain is slightly less related to the other companion strains. The association
      between the companion and the myxobacterium including the sporangioles was
      determined by in situ hybridization with fluorescently labeled rRNA probes and
      scanning confocal laser microscopy. Based on these results, there are indications
      that the companion strains may survive environmental stress by inclusion in the
      aggregates and in the sporangioles of the myxobacterium.

PMID- 9023950
TI  - Competition for cellulose among three predominant ruminal cellulolytic bacteria
      under substrate-excess and substrate-limited conditions.
AB  - Three predominant ruminal cellulolytic bacteria (Fibrobacter succinogenes S85,
      Ruminococcus flavefaciens FD-1, and Ruminococcus albus 7) were grown in different
      binary combinations to determine the outcome of competition in either cellulose
      excess batch culture or in cellulose-limited continuous culture. Relative
      populations of each species were estimated by using signature membrane-associated
      fatty acids and/or 16S rRNA-targeted oligonucleotide probes. Both F. succinogenes
      and R. flavefaciens coexisted in cellulose-excess batch culture with similar
      population sizes (58 and 42%, respectively; standard error, 12%). By contrast,
      under cellulose limitation R. flavefaciens predominated (> 96% of total cell
      mass) in coculture with F. succinogenes, regardless of whether the two strains
      were inoculated simultaneously or whether R. flavefaciens was inoculated into an
      established culture of F. succinogenes. The predominance of R. flavefaciens over
      F. succinogenes under cellulose limitation is in accord with the former's more
      rapid adherence to cellulose and its higher affinity for cellodextrin products of
      cellulose hydrolysis. In batch cocultures of F. succinogenes and R. albus, the
      populations of the two species were similar. However, under cellulose limitation,
      F. succinogenes was the predominant strain (approximately 80% of cell mass) in
      cultures simultaneously coinoculated with R. albus. The results from batch
      cocultures of R. flavefaciens and R. albus were not consistent within or among
      trials: some experiments yielded monocultures of R. albus (suggesting production
      of an inhibitory agent by R. albus), while others contained substantial
      populations of both species. Under cellulose limitation, R. flavefaciens
      predominated over R. albus (85 and 15%, respectively), as would be expected by
      the former's greater adherence to cellulose. The retention of R. albus in the
      cellulose-limited coculture may result from a combination of its ability to
      utilize glucose (which is not utilizable by R. flavefaciens), its demonstrated
      ability to adapt under selective pressure in the chemostat to utilization of
      lower concentrations of cellobiose, a major product of cellulose hydrolysis, and
      its possible production of an inhibitory agent.

PMID- 9023951
TI  - Competition for cellobiose among three predominant ruminal cellulolytic bacteria
      under substrate-excess and substrate-limited conditions.
AB  - The ruminal cellulolytic bacteria Ruminococcus flavefaciens FD-1 and Fibrobacter
      succinogenes S85 coexisted in substrate-excess coculture with about equal
      population size, but R. flavefaciens outcompeted F. succinogenes for cellobiose
      in the substrate-limited cocultures whether the two strains were coinoculated or
      a steady-state culture of F. succinogenes was challenged by R. flavefaciens. This
      outcome of competition between these two strains is due to a classical pure and
      simple competition mechanism based on affinity for cellobiose. Although the
      population size of F. succinogenes was much higher (> 70%) than that of another
      cellulolytic species, Ruminococcus albus 7 in substrate-excess coculture, F.
      succinogenes was replaced by a population of R. albus in the substrate-limited
      coculture in both coinoculation and challenge experiments. R albus outcompeted F.
      succinogenes, apparently due to selection in the chemostat of a population of R.
      albus with a higher affinity for cellobiose. R. albus also outcompeted R.
      flavefaciens under substrate-limited conditions.

PMID- 9023952
TI  - Regulated system for heterologous gene expression in Penicillium chrysogenum.
AB  - A system for regulated heterologous gene expression in the filamentous fungus
      Penicillium chrysogenum was established. This is the first heterologous
      expression system to be developed for this organism. Expression of a recombinant
      fungal xylanase gene (xylp) and the cDNA for the human tear lipocalin (LCNI) was
      achieved by placing the encoding sequences under the control of the repressible
      acid phosphatase gene (phoA) promoter of P. chrysogenum. Secreted recombinant
      proteins were detected in the growth media of transformed P. chrysogenum cells by
      means of bioassays, zymogramography, and Western blotting. Levels of
      transcription and amounts of recombinant proteins secreted varied among
      transformants, mainly due to the copy number and the integration site of the
      expression vector on the fungal chromosome.

PMID- 9023953
TI  - Analysis of whole-cell fatty acid profiles of verotoxigenic Escherichia coli and
      Salmonella enteritidis with the microbial identification system.
AB  - Differentiation of strains within bacterial species, based on gas chromatographic
      analysis of whole-cell fatty acid profiles, was assessed with 115 strains of
      verotoxigenic Escherichia coli and 315 strains of Salmonella enteritidis. Fatty
      acid-based subgroups within each of the two species were generated. Variability
      of fatty acid profiles observed in repeat preparations from the same strain
      approached that observed between subgroups, limiting the usefulness of using
      fatty acid profiles to subgroup verotoxigenic E. coli and S. enteritidis strains.

PMID- 9023954
TI  - Mutational analysis of the feedback sites of phenylalanine-sensitive 3-deoxy-D
      arabino-heptulosonate-7-phosphate synthase of Escherichia coli.
AB  - In Escherichia coli, aroF, aroG, and aroH encode 3-deoxy-D-arabino-heptulosonate
      7-phosphate synthase isozymes that are feedback inhibited by tyrosine,
      phenylalanine, and tryptophan, respectively. In vitro chemical mutagenesis of the
      cloned aroG gene was used to identify residues and regions of the polypeptide
      essential for phenylalanine feedback inhibition.

PMID- 9023955
TI  - Two amino acid amidohydrolase genes encoding L-stereospecific carbamoylase and
      aminoacylase are organized in a common operon in Bacillus stearothermophilus.
AB  - The L-carbamoylase gene (amaB) upstream of the previously detected L-aminoacylase
      gene (amaA) in the Bacillus stearothermophilus NCIB8224 strain was identified in
      this study. The amaB and amaA genes are cotranscribed as a single mRNA from the
      same transcriptional start. The two-ama-gene operon is conserved in B.
      stearothermophilus strains. A cross-activity of L-carbamoylase towards respective
      substrates for L-aminoacylase supports the hypothesis of a common ancestor for
      both amino acid amidohydrolase genes.

PMID- 9023956
TI  - Limitations of highly sensitive enzymatic presence-absence tests for detection of
      waterborne coliforms and Escherichia coli.
AB  - This study presents evidence for the unfeasibility of enzymatic presence-absence
      tests to detect one total coliform or one Escherichia coli organism in 100 ml of
      drinking water within a working day. The results of field trials with prototype
      chemiluminometric procedures indicated that the sensitivity-boosting measures
      that are essential to achieve the required speed compromise the specificity of
      the tests.

PMID- 9023957
TI  - Comparison of commercially available kits with standard methods for detection of
      Salmonella strains in foods.
AB  - Six commercial kits were compared with the U.S. Food and Drug Administration
      (USFDA) method and the Japanese standard method for Salmonella isolation in
      foods. When only Salmonella serovars were tested, many of the methods performed
      well; however, when foods were artificially inoculated, only the USFDA method and
      immunomagnetic separation coupled with the xylose-lysine-brilliant green agar
      method (MS-XLBG) could positively detect Salmonella serovars. All seven wild-type
      Salmonella serovars were detected by the USFDA method, and the MS-XLBG method
      detected salmonellae from six samples.

PMID- 9023958
TI  - A recombinase-mediated system for elimination of antibiotic resistance gene
      markers from genetically engineered Bacillus thuringiensis strains.
AB  - A TnpI-mediated site-specific recombination system to construct genetically
      modified Bacillus thuringiensis strains was developed. Recombinant B.
      thuringiensis strains from which antibiotic resistance genes can be selectively
      eliminated were obtained in vivo with a new vector based on the specific
      resolution site of transposon Tn4430. For example, a cryIC gene, whose product is
      active against Spodoptera littoralis, was introduced into B. thuringiensis Kto
      harboring a cryIA(c) gene active against Ostrinia nubilalis. The resulting strain
      had a broader activity spectrum than that of the parental strain. It contained
      only B. thuringiensis DNA and was free of antibiotic resistance genes. This
      should facilitate regulatory approval for its development as a commercial
      biopesticide.

PMID- 9023960
TI  - Cellobiose dehydrogenase from Phanerochaete chrysosporium is encoded by two
      allelic variants.
AB  - The complete nucleotide sequences of two alleles of cellobiose dehydrogenase, cdh
      1 (3,627 bp) and cdh-2 (3,623 bp), from Phanerochaete chrysosporium OGC101 are
      reported. The nucleotide sequences of cdh-1 and cdh-2 exhibit 97% similarity. A
      total of eighty-six point mutations between cdh-1 and cdh-2 are observed. Both
      alleles have 14 exons, and the introns are located at exactly the same positions.
      The translation products of these alleles have identical amino acid sequences.
      Restriction fragment length polymorphism analyses of homokaryotic derivatives
      show segregation of the CDH alleles.

PMID- 9023959
TI  - In vitro stabilization and in vivo solubilization of foreign proteins by the beta
      subunit of a chaperonin from the hyperthermophilic archaeon Pyrococcus sp. strain
      KOD1.
AB  - The gene encoding the beta subunit of a molecular chaperonin from the
      hyperthermophilic archaeon Pyrococcus sp. strain KOD1 (cpkB) was cloned,
      sequenced, and expressed in Escherichia coli. The cpkB gene is composed of 1,641
      nucleotides, encoding a protein (546 amino acids) with a molecular mass of 59,140
      Da. The enhancing effect of CpkB on enzyme stability was examined by using
      Saccharomyces cerevisiae alcohol dehydrogenase (ADH). Purified recombinant CpkB
      prevents thermal denaturation and enhances thermostability of ADH. CpkB requires
      ATP for its chaperonin function at a low CpkB concentration; however, CpkB
      functions without ATP when present in excess. In vivo chaperonin function for the
      solubilization of insoluble proteins was also studied by coexpressing CpkB and
      CobQ (cobryic acid synthase), indicating that CpkB is useful for solubilizing the
      insoluble proteins in vivo. These results suggest that the beta subunit plays a
      major role in chaperonin activity and is functional without the alpha subunit.

PMID- 9023961
TI  - Structural gene (nirS) for the cytochrome cd1 nitrite reductase of Alcaligenes
      eutrophus H16.
AB  - Denitrification by Alcaligenes eutrophus H16 is genetically linked to megaplasmid
      pHG1. Unexpectedly, the gene encoding the nitrite reductase (nirS) was identified
      on chromosomal DNA. The nirS product showed extensive homology with periplasmic
      nitrite reductases of the heme cd1-type. Disruption of nirS abolished nitrite
      reducing ability, indicating that NirS is the enzyme essential for
      denitrification in A.eutrophus.

PMID- 9023962
TI  - Novel group within the kingdom Crenarchaeota from boreal forest soil.
AB  - We report here the results of phylogenetic analysis of archaeal 16S rRNA gene
      sequences amplified by PCR with Archaea-specific primers with mixed-population
      DNA extracted directly from forest soil used as a template. Nucleotide signature
      and phylogenetic analyses show that the sequences obtained belong to the domain
      Archaea and form a new cluster. Its phylogenetic position suggests that sequences
      are from a previously undescribed terrestrial group within the kingdom
      Crenarchaeota.

PMID- 9023963
TI  - Introduction of anaerobic dechlorinating bacteria into soil slurry microcosms and
      nested-PCR monitoring.
AB  - Desulfomonile tiedjei and Desulfitobacterium dehalogenans were chosen as model
      bacteria to demonstrate the introduction of an anaerobic microbia reductive
      dechlorination activity into nonsterile soil slurry microcosms by inoculation. De
      novo 3-chlorobenzoate dechlorination activity was established with the bacterium
      D. tiedjei in microcosms normally devoid of this dechlorination capacity. The
      addition of D. tiedjei to microcosms supplemented with 20 mM pyruvate as the
      cosubstrate resulted in total biotransformation of 1.5 mM 3-chlorobenzoate within
      7 days. The introduction of the bacterium Desulfitobacterium dehalogenans into
      nonsterile microcosms resulted in a shortening of the period required for
      dechlorination activity to be established. In microcosms inoculated with
      Desulfitobacterium dehalogenans, total degradation of 6 mM 3-chloro-4-hydroxy
      phenoxyacetic acid (3-Cl-4-OHPA) was observed after 4 days in contrast to the
      result in noninoculated microcosms, where the total degradation of 3-Cl-4-OHPA by
      indigenous microorganisms was observed after 11 days. Both externally introduced
      bacterial strains were detected in soil slurry microcosms by a nested-PCR
      methodology.

PMID- 9023965
TI  - Constituents of a fern, Diplazium subsinuatum. II. Structure elucidation of five
      new hopane-triterpene glycosides.
AB  - From whole fern, Diplazium subsinuatum (Wall. ex Hook. et Grev.) Tagawa, two new
      hopane-triterpene glycosides named diplaziosides III and IV were isolated,
      together with three new hopane glycosides with acetylated sugars. The structures
      of diplaziosides III and IV were established as (22S)-24-O-alpha-L
      arabinofuranosyl-(1 --> 2)- [beta-D-glucopyranosyl-(1 --> 6)]-beta-D
      glucopyranosyl-20 alpha-O-beta-D-glucopyranosyl-30-hydroxyhopan-28-oic acid (1)
      and (22R)-24-O-alpha-L-arabinofuranosyl-(1-->2)-[beta-D-glucopyranosyl-(1--> 6)]
      beta-D-glucopyranosyl-30-carboxy-17-hydroxy-hopano-28,22-lacto ne (2),
      respectively, on the basis of spectral evidence. Diplazioside III (1) is novel
      not only in its glycoside structure, but also in its triterpene structure and
      moreover, 1 provides the first instance of a naturally occurring bisdesmoside
      with a hopane aglycone. The structures (3a, 3b, and 4a) of the acetylated
      glycosides were also elucidated, and this is the first report of naturally
      occurring acetates of hopane glycosides.

PMID- 9023964
TI  - Alkaline stress response in Enterococcus faecalis: adaptation, cross-protection,
      and changes in protein synthesis.
AB  - The alkaline shock response in Enterococcus faecalis was studied in this work.
      Cells adapted to an optimum pH of 10.5 were tolerate to pH 11.9 conditions but
      acquired sensitivity to acid damage. An analysis of stress proteins revealed that
      37 polypeptides were amplified. Two of these are DnaK and GroEL. The combined
      results show that bile salts and alkaline stress responses are closely related.

PMID- 9023966
TI  - A reductive acidolysis final deprotection strategy in solid phase peptide
      synthesis based on safety-catch protection.
AB  - A reductive acidolysis final deprotection strategy in solid phase peptide
      synthesis was developed using a new safety-catch type of semi-permanent
      protecting groups and new linkers which were derived from 4-methylsulfinylbenzyl
      protection. This new strategy was based on a two-dimensional protection scheme
      employing acid-labile temporary and acid-stable but reductive acidolysis
      cleavable semi-permanent protecting groups. By using this strategy, we
      successfully synthesized four model peptides, of which two contained C-terminal
      amide.

PMID- 9023968
TI  - Antisweet natural products. XII. Structures of sitakisosides XI-XX from
      Stephanotis lutchuensis Koidz. var. japonica.
AB  - From the fresh stem of Stephanotis lutchuensis var. japonica, ten new oleanane
      type triterpenoid glycosides, named sitakisosides XI-XX (1-10), were isolated.
      Their structures were determined on the basis of spectroscopic data and chemical
      evidence. The results show that all have a 3-O-beta-D-xylopyranosyl(1 --> 6)-beta
      D-glucopyranosyl(1 --> 6)- beta-D-glucopyranosyl moiety and the aglycones of
      sitakisosides XI-XV, XVI and XVII, XVIII and XIX, and XX are sitakisogenin,
      chichipegenin, marsglobiferin and longispinogenin, respectively. Sitakisosides XI
      XIII, XVI and XVIII, having an acyl group, showed antisweet activity.

PMID- 9023967
TI  - Efficient and beta-stereoselective synthesis of 4(5)-methyl-5(4)-(5-amino-5-deoxy
      beta-D-ribofuranosyl)imidazole and related compounds exhibiting antiulcer
      activity.
AB  - The reaction of 2,3,5-tri-O-benzyl-D-ribose with the lithium salt of an imidazole
      derivative gave an adduct 17RS. Treatment of 17RS with 1.5N HCl in refluxing
      tetrahydrofuran gave the beta-4(5)-ribofuranosylimidazole 19 (35%) and the
      ribosylimidazole 18 (51%). The latter was converted into beta-19 in 86% yield by
      the Mitsunobu cyclization. This synthetic method produced only the desired beta
      anomer. Protection of the imidazole nitrogen of 19 with an ethoxycarbonyl group
      followed by debenzylation gave 21, which was successively derived to the 5'-amino
      derivative 1 via the 5'-substituted phthalimide 23, followed by hydrazine
      degradation in excellent yield. Compound 1 was then converted into the 5'
      cyanoguanidine 2 in 79% yield. The 5'-amino derivatives 3-9 lacking a methyl
      group were efficiently synthesized. Among them, the cyanoguanidine 5 and
      phenylthiourea 8 exhibited antiulcer activities with half the efficacy of
      cimetidine. The molecular conformation of 5 was determined by X-ray structure
      analysis.

PMID- 9023970
TI  - Medicinal foodstuffs. IV. Fenugreek seed. (1): structures of trigoneosides Ia,
      Ib, IIa, IIb, IIIa, and IIIb, new furostanol saponins from the seeds of Indian
      Trigonella foenum-graecum L.
AB  - Six new furostanol saponins called trigoneosides Ia, Ib, IIa, IIb, IIIa, and IIIb
      were isolated from a medicinal foodstuff, fenugreek seed, the seed of Trigonella
      foenum-graecum L. (Leguminosae) originating from India, together with two known
      saponins, glycoside D and trigofoenoside A. The structures of trigoneosides Ia,
      Ib, IIa, IIb, IIIa, and IIIb were determined on the basis of chemical and
      physicochemical evidence as 26-O-beta-D-glucopyranosyl-(25S)-5 alpha-furostane-2
      alpha,3 beta,22 zeta,26-tetraol 3-O-[beta-D-xylopyranosyl (1 --> 6)]-beta-D
      glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)- 5 alpha-furostane-2 alpha,3
      beta,22 zeta,26-tetraol 3-O-[beta-D-xylopyranosyl (1-->6)]-beta-D
      glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)-5 beta-furostane-3 beta,22
      zeta,26-triol 3-O-[beta-D-xylopyranosyl (1 --> 6)]-beta-D-glucopyranoside, 26-O
      beta-D-glucopyranosyl-(25R)-5 beta-furostane-3 beta,22 zeta,26-triol 3-O-[beta-D
      xylopyranosyl (1-->6)]-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25S)-5
      alpha-furostane-3 beta,22 zeta,26-triol 3-O-[alpha-L-rhamnopyranosyl(1 --> 2)]
      beta-D-glucopyranoside, and 26-O-beta-D-glucopyranosyl-(25R)-5 alpha-furostane-3
      beta,22 zeta,26-triol 3-O-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D
      glucopyranoside, respectively.

PMID- 9023969
TI  - Antitumor agents. 168. Dysoxylum cumingianum. IV. The structures of
      cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane
      type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human
      cancer cell lines.
AB  - Nine new triterpene glucosides, named cumingianosides G-O (4-7, 9, 12-15),
      containing a 14,18-cycloapotirucallane-type skeleton were isolated from a
      cytotoxic fraction of the leaves of Dysoxylum cumingianum. The structures of the
      new compounds were established on the basis of chemical and spectral
      examinations. Evaluation of the cytotoxic activity of cumingianosides G-O showed
      that cumingianoside M exhibited significant (< 4 microM) cytotoxicity, especially
      against leukemia and melanoma cell lines.

PMID- 9023971
TI  - Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. Synthesis and structure
      activity relationships of 9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one
      derivatives.
AB  - Novel 9-methyl-4,9-dihydrothiopyrano[2,3-b]indol-4-one derivatives 2b-e, 3
      methylene-9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-on e derivatives 3b
      e and 9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one derivatives 4a-e
      were prepared. The 5-hydroxytryptamine (5-HT3) receptor-antagonistic activities
      of these compounds were evaluated by using the von Bezold-Jarisch reflex test (B.
      J. reflex, rats) and the contractile response to 5-HT in the isolated distal
      colon (guinea pig). The 5-ethyl-4-imidazolyl derivative 4d was found to be 79
      times more potent than ondansetron 1 in the B. J. reflex test (ID50 = 0.048
      microgram/kg, i.v.), and the 5-methyl-4-imidazolyl derivative 4c was found to be
      126 times more potent than 1 in the colonic contraction (IC50 = 0.0062 microM)
      assay.

PMID- 9023972
TI  - An improvement of neural networks applied to pharmaceutical problems.
AB  - In applying the neural network to the classification problem in pharmacology, we
      adopt an extended back-propagation (EBP) learning which adjusts the parameters
      appearing in an activation function, as well as the weights. The results of
      simulations show that such an extended learning speeds up the learning process as
      compared with the conventional basic back-propagation procedure, irrespective of
      the initial values of the parameters, which is extremely useful in the practical
      application of the neural network in the pharmaceutical field. We have also found
      that use of Morita's activation function beyond the sigmoid type further
      accelerates the EBP learning in some cases.

PMID- 9023973
TI  - Synthesis and biological evaluation of a new reversely linked type of dual
      histamine H2 and gastrin receptor antagonist.
AB  - In an attempt to improve the low oral absorbability of previously reported dual
      histamine H2 and gastrin receptor antagonists, compounds of a different type were
      synthesized and evaluated for biological activity. These new compounds bear a
      histamine H2 receptor antagonist (H2A) pharmacophore moiety attached to a gastrin
      receptor antagonist (GA) pharmacophore moiety in a reversed manner, namely the
      head-to-head manner, different from the previously reported head-to-tail manner.
      These new hybrid compounds were classified into three types: type I, the regular
      amide type bearing a roxatidine moiety; type II, the reversed amide type bearing
      a roxatidine moiety; and type III, hybrid compounds bearing a famotidine moiety
      directly connected to a GA moiety without a spacer. Among them, only (R)-1-[3-(N'
      (4-[2-(N-aminosulfonylamidino)ethylthiomethyl] thiazol-2-yl)
      guanidinomethyl)phenyl]-3- (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4
      benzodiazepin-3-yl) ure a (42), belonging to type III, showed a weak but distinct
      histamine H2 receptor-antagonistic activity as well as a modest gastrin receptor
      antagonistic activity. Of most importance was the finding that this compound
      showed a weak but clearly improved in vivo oral antigastric acid secretory
      activity as a result of the structural changes, including the decreased molecular
      weight.

PMID- 9023974
TI  - Synthesis and biological evaluation of novel cyclic enediyne compounds related to
      dynemicin A as antitumor agents.
AB  - Novel cyclic enediyne compounds, which are simple functional analogs of dynemicin
      A (1) having the bicyclo-[7.3.1]tridec-4-ene-2,6-diyne system, were synthesized
      and evaluated for the DNA-cleaving ability, in vitro cytotoxicity and in vivo
      antitumor activity. All of the sulfones 19-24, which were equipped with a 2
      (arylsulfonyl)-ethoxycarbonyl group or the 2-(methylsulfonyl)ethoxycarbonyl group
      as a triggering device, showed both potent DNA-cleaving activity and cytotoxicity
      against various tumor cell lines. However, these compounds were entirely inactive
      or only slightly active against murine P388 leukemia in mice. On the other hand,
      the enediyne 2a having a phenyl carbamate moiety as a stable N-protecting group
      showed effective antitumor activity both in vitro and in vivo. In particular, it
      exhibited significant antitumor activity against Lewis lung carcinoma in mice.
      These results show that the character of the carbamate moiety of the cyclic
      enediynes strikingly affects their biological activities, that is, the
      sulfonylethyl carbamate moiety is an effective triggering device for both DNA
      cleaving activity and cytotoxicity, and the phenyl carbamate moiety is
      significant for antitumor activity in vivo. As part of a mechanistic study, the
      reactivities of 2a and 21 were examined under a weakly basic condition (pH 9.3);
      both compounds failed to give the Bergman cycloaromatization product.

PMID- 9023975
TI  - Synthesis and antitumor activity of quaternary salts of 2-(2'-oxoalkoxy)-9
      hydroxyellipticines.
AB  - Various kinds of water-soluble quaternary salts of 2-(2'-oxoalkoxy)-9
      hydroxyellipticines were synthesized in a search for compounds with potent
      antitumor activity and low toxicity. Some compounds exhibited more potent
      antitumor activities than elliptinium (1) and SUN 4599 (3). In particular, 2-(3'
      methoxy-2'-oxopropanoxy)-9- hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium
      bromide (4d) showed potent antitumor activities against P388 leukemia, colon 26,
      and Lewis lung carcinoma.

PMID- 9023976
TI  - New neplanocin analogues. IX. A practical preparation of (6'R)-6'-C
      methylneplanocin A (RMNPA), a potent antiviral agent, and the determination of
      its 6'-configuration. Diastereoselective deamination by adenosine deaminase.
AB  - We previously synthesized (6'R)- and (6'S)-6'-C-methylneplanocin A's (2a and 2b,
      respectively), and found that one of them has a potent antiviral activity, though
      its 6'-configuration has not been confirmed. This report describes the
      determination of the 6'-configuration and practical preparation of the
      antivirally active diastereomer. The 6'-configuration of the active diastereomer
      was determined as R by the modified Mosher's method as well as by synthesizing 2b
      from the known cyclopentenone derivative 10. A practical method for preparing the
      6'R-diastereomer was developed by using diastereoselective deamination with Ado
      deaminase as the key step. Treatment of the diastereomeric mixture of 2a and 2b,
      which was prepared via an addition reaction of Me3Al with the 6'-formyl
      derivative 3, with Ado deaminase from calf intestine, deaminated 2b selectively
      to give the corresponding (6'S)-inosine congener 5, and left the desired 2a not
      deaminated. After silica gel column chromatography, 2a was obtained in a pure
      form.

PMID- 9023977
TI  - Heterocyclic analogues of quinone methide: preparation and cytotoxicity of 3-oxo
      3H-pyrazolo[1,5-a]indole derivatives.
AB  - A series of 3-oxo-3H-pyrazolo[1,5-a]indole derivatives was prepared and
      characterized as heterocyclic analogues of quinone methide. These compounds
      showed some cytotoxicity to cancer cells, but were ineffective in an in vivo test
      against murine leukemia L1210.

PMID- 9023978
TI  - The effects of glucose oligomers (maltodextrins) on freeze-drying liposomes.
AB  - Liposomes were freeze-dried with glucose oligomers (maltodextrins) consisting of
      2 (maltose) to 7 (maltoheptaose) glucoside units, and the effects of the
      glucoside unit number of the maltodextrin on the lyophilization of the liposomes
      were investigated. When the molar ratio of the glucoside units of maltodextrins
      to lipids was reduced below 6, two distinct endotherms were observed after
      annealing the freeze-dried L-alpha-dipalmitoylphosphatidylcholine (DPPC) liposome
      by differential scanning calorimetry (DSC). When the molar ratio was raised above
      6, only the lower of the two endotherms was observed in all maltodextrins tested.
      At a molar ratio of 6, the gel to liquid crystalline transition temperature (Tm)
      of the first scan of these samples was measured. The Tm with maltose was observed
      to be ca. 65 degrees C, whereas the Tm with the other maltodextrins was observed
      to increase as the number of glucoside units was increased. Using Fourier
      transform IR, the phosphate asymmetric stretching band of DPPC liposomes
      lyophilized with these maltodextrins was observed to shift to lower frequencies.
      In all cases, the phosphate asymmetric stretching was observed to be roughly 1240
      and 1224 cm-1 in the presence of these saccharides. The ratio of the absorbance
      at 1224 to that at 1240 cm-1 of DPPC liposomes freeze-dried with maltose was
      greater than the ratio of those stabilized with any of the other maltodextrins
      tested. These results suggest that the rate of hydrogen bonding between the
      phosphate of the lipid and maltodextrins was highest when maltose was used as the
      cryoprotectant. Because of this interaction, the space between the lipid
      molecules may become wider, causing an increase in the flexibility of the
      liposomal membrane.

PMID- 9023979
TI  - Synthesis and biological activity of a 1 alpha,25-dihydroxyvitamin D2 analog
      bearing an amide group in the side-chain.
AB  - Synthesis of a 1 alpha,25-dihydroxyvitamin D2 analog (3), in which the double
      bond in the side-chain is replaced by an amide group, is described. Condensation
      of a carboxylic acid (8) with an amine (6) gave an amide (9), which in turn led
      to 3 via several steps. The analog (3) could not bind to the chick cytosol
      vitamin D receptor, which indicated the importance of the hydrophobic interaction
      of the C(22)-C(23) double bond in 1 alpha,25-dihydroxyvitamin D2 (2) with the
      vitamin D receptor.

PMID- 9023980
TI  - Antitumor agents. 169 Dysoxylum cumingianum. V. Cumingianosides P and Q, new
      cytotoxic triterpene glucosides with an apotirucallane-type skeleton from
      Dysoxylum cumingianum.
AB  - Detailed chemical studies on the cytotoxic fraction from the leaves of Dysoxylum
      cumingianum have resulted in the isolation of two new triterpene glucosides,
      cumingianosides P (18) and Q (19), with an apotirucallane-type skeleton. The
      structures of 18 and 19 were determined by spectral examinations, and by
      conversion of cumingianosides C (3) and A (1) into 18 and 19, respectively. The
      cytotoxicities of cumingianosides P and Q against over 50 human cancer cell lines
      were evaluated. Cumingianoside P exhibited significant (EC50 < 4 microM)
      cytotoxicity against 37 human cancer cell lines. Among them, the UO-31 (renal
      cancer) cell line was the most sensitive to this compound (EC50 0.267 microM). In
      contrast, cumingianoside Q showed selective cytotoxicity against NCI-H522 (non
      small cell lung cancer) cells with an EC50 value of 1.67 microM, and exhibited no
      cytotoxicity (EC50 > 10 microM) against most of the remaining cancer cell lines.

PMID- 9023981
TI  - The germ line and development.

PMID- 9023982
TI  - Origin of primordial germ cells in the prestreak chick embryo.
AB  - The temporal and spatial pattern of segregation of the avian germline from the
      formation of the area pellucida to the beginning of primitive streak formation
      (stages VII-XIV, EG&K) was investigated using the culture of whole embryos and
      central and peripheral embryo fragments on vitelline membranes at stages VII-IX,
      immunohistological analysis of whole mount embryos and sections with monoclonal
      antibodies MC-480 against stage-specific embryonic antigen-1 (SSEA-1) and EMA-1,
      and with the culture of dispersed blastoderms at stages IX-XIV with and without
      on STO feeder layer. Whole embryos at intrauterine stages developed up to the
      formation of the primitive streak despite the absence of area pellucida
      expansion. Primordial germ cells (PGCs) appeared in the cultures of whole embryos
      and only in central fragments containing a partially formed area pellucida at
      stages VII-IX. When individual stage IX-XIV embryos were dispersed and cultured
      without a feeder layer, 25-45 PGCs/embryo were detected only with stage X-XIV,
      but not with stage IX blastoderms. However, the culture of dispersed cells from
      the area pellucida of stages IX-XIII on STO feeder layers yielded about 150
      PGCs/embryo. The carbohydrate epitopes recognized by anti-SSEA-1 and EMA-1 first
      appeared at stage X on cells in association with polyingressing cells on the
      ventral surface of the epiblast and later on the dorsal surface of the hypoblast.
      The SSEA-1-positive hypoblast cells gave rise to chicken PGCs when cultured on a
      feeder layer of quail blastodermal cells. From these observations, we propose
      that the segregation and development of avian germline is a gradual, epigenetic
      process associated with the translocation of SSEA-1/EMA-1-positive cells from the
      ventral surface of the area pellucida at stage X to the dorsal side of the
      hypoblast at stages XI-XIV.

PMID- 9023983
TI  - Mouse ret finger protein (rfp) proto-oncogene is expressed at specific stages of
      mouse spermatogenesis.
AB  - Many proteins involved in the regulation of cell growth and differentiation
      possess structural motifs that participate in specific molecular interactions.
      The human rfp (ret finger protein) has a tripartite motif, consisting of two
      novel zinc fingers (the RING linger and the B box) and a coiled-coil domain, and
      belongs to the B box zinc finger protein family. Rfp becomes oncogenic when its
      tripartite motif is recombined with the tyrosine kinase domain from the c-ret
      proto-oncogene. To further understand the function of rfp during normal
      development and cellular differentiation, we cloned the mouse rfp cDNA and
      analyzed its pattern of expression and subcellular distribution. We found that
      the mouse rfp cDNA shared a 98.4% homology with the human sequence. The gene
      mapped to human chromosome 6 and mouse chromosome 13 indicating that it was
      linked to a several other genes encoding proteins that possess common domains.
      rfp transcripts and protein were ubiquitous in day 10.5-13.5 mouse embryos,
      however, they were restricted in adult mice, with the highest level of expression
      in pachytene spermatocytes and round spermatids of differentiating sperm. The rfp
      protein was detected within cell nuclei as nuclear bodies similar to the PODs
      (PML oncogenic domains) observed with another B box family member, PML
      (promyelocytic leukemia protein). These results suggest that rfp may function in
      the regulation of cell growth and differentiation during mouse embryogenesis and
      sperm differentiation.

PMID- 9023984
TI  - Analysis of the cDNA and encoded protein of the human testis-specific PGK-2 gene.
AB  - Because of their unique function, germ cells require unique gene products. Thus,
      although the glycolytic enzyme phosphoglycerate kinase (PGK) is required in all
      metabolically active cell types, there are two functional PGK genes in the
      mammalian genome, one, PGK-1, that is X-linked and ubiquitously expressed in all
      somatic tissues, and a second, PGK-2, that is autosomal and expressed only in
      spermatogenic cells. Expression of the PGK-2 gene may function solely to
      compensate for repressed expression of the PGK-1 gene due to X-chromosome
      inactivation in spermatocytes. Alternative y, the PGK-2 gene could encode an
      isozyme with unique characteristics that are beneficial to spermatozoa. We have
      isolated a cDNA of the human PGK-2 gene and used this as probe to demonstrate
      that transcription of this gene in spermatocytes and spermatids coincides with a
      period of repressed transcription of the X-linked PGK-1 gene during
      spermatogenesis in the human testis. We have also analyzed the amino acid
      sequence and protein characteristics of the PGK-2 isozyme deduced from this cDNA
      and compared them with that of the human PGK-1 isozyme to show that known
      structural and functional motifs are conserved in both proteins. Finally, we have
      examined the distribution of the PGK-1 and PGK-2 isozymes during spermatogenesis
      in the mouse to show that while the PGK-2 protein does not appear to possess any
      unique intracellular localization signal, it is more stable in vivo than the PGK
      1 protein.

PMID- 9023985
TI  - Antenna to leg transformation: dynamics of developmental competence.
AB  - We explore the transformation of antenna to leg in Drosophila melanogaster, using
      ectopically expressed transgenes with heat shock promoters: heat shock
      Antennapedia, heat shock Ultrabithorax, and heat shock mouse Hox A5. We
      determined the frequency of transformation of several leg markers in response to
      Antennapedia protein delivered by heat shock at different times and doses. We
      also studied stage-specific responses to the transgene, heat shock mouse Hox A5.
      Results show that each marker has its own stage and dose-specific pattern of
      response. The same marker could pass through a period of high-dose inhibition
      followed by a dose-independent response and then a positive dose-dependent phase.
      The heat shock-induced transgenes and spineless aristapedia transformed the
      apterous enhancer trap antenna disc expression pattern toward the pattern found
      in leg discs. These results are considered in relation to developmental
      competence-the ability of developing tissue to respond to internal or external
      influences. The results suggest that all genes tested interact with the same
      competence system and that at least two classes of mechanisms are associated with
      antenna to leg transformation: one comprises global mechanisms that permit
      transformation over approximately 24 hr; the second class of mechanisms act very
      locally and are responsible for changes in dose response on the order of 4-8 hr.

PMID- 9023986
TI  - Engrailed gene dosage determines whether certain recessive cubitus interruptus
      alleles exhibit dominance of the adult wing phenotype in Drosophila.
AB  - The cubitus interruptus (ci) locus of Drosophila melanogaster is needed for
      normal development. Some mutants of this gene result in embryonic lethality,
      while others just disrupt adult wing veins. While undertaking a genetic screen
      for additional ci mutations that affect the wing veins, we recovered a modifier
      mutation on chromosome two that produced a ci phenotype in recessive ci
      heterozygotes (ci(recessive)/+). We identified the modifier mutation as an allele
      of engrailed and have called it engrailed-enhancer of cubitus interruptus
      (enEnci). As a double heterozygote (en-/+; ci-/+) this new en allele dominantly
      generates a ci wing vein phenotype. As a double heterozygote, it also enhances
      the ci wing vein phenotype of the dominant alleles ciW and ciCe2, but not ciD.
      Other loss-of-function en alleles also enhance the ci phenotype, with the en
      lethal alleles (and deletions) showing the strongest effect, while the homozygous
      viable en alleles show weaker enhancement. Strong en- alleles failed to induce a
      ci phenotype with heterozygotes of ci recessive lethal alleles l(4)13, l(4)17, or
      ciDrev, which are loss-of-function mutations. This supports a previous proposal
      that the ci wing vein phenotype is not due to loss of ci+ function, as would be
      expected for most recessive alleles. Instead, the adult wing vein abnormality is
      due to ectopic expression (or de-repression) of the ci transcript in the
      posterior compartment of the wing disc. We also observed that en-/+ heterozygotes
      could induce a ci phenotype in situations where the ci+ locus is either unpaired
      or hemizygous. Since loss of one en+ gene dose enhanced the ci phenotype, three
      doses of en+ were tested and found to suppress expression of the ci phenotype in
      ci1 homozygotes and ciW heterozygotes. These observations show that correct
      regulation of the ci gene involves more than the simple interaction of upstream
      regulatory elements. some pairing, pairing dependent gene repression, position
      effects.

PMID- 9023987
TI  - Isolation and characterization of glycogen synthase in Dictyostelium discoideum.
AB  - We have partially purified the protein and isolated the glcS gene for glycogen
      synthase in Dictyostelium. glcS mRNA is present throughout development and is the
      product of a single gene coding for 775 amino acids, with a predicted molecular
      mass of 87 kD. The sequence is highly similar to glycogen synthase from human
      muscle, yeast, and rat liver, diverging significantly only at the amino and
      carboxy termini. Phosphorylation and UDPG binding sites are conserved, with K(m)
      values for UDPG being comparable to those determined for other organisms, but in
      vitro phosphorylation failing to convert between the G6P-dependent (D) and 
      independent (I) forms. Enzyme activity is relatively constant throughout the life
      cycle: the I form of the enzyme isolates with the soluble fraction in amoebae,
      switches to the D form, becomes pellet-associated during early development, and
      finally reverts during late development to the I form, which again localizes to
      the soluble fraction. Deletion analysis of the promoter reveals a GC-rich element
      which, when deleted, abolishes expression of glcS.

PMID- 9023988
TI  - P-element inserts in transgenic flies: a cautionary tale.
AB  - The fruitfly, Drosophila melanogaster, can be transfected with P-elements and
      induced to overexpress a transfected gene whose impact on lifespan can be
      measured. Here, it is reported that in previous experiments a transfected gene
      was not expressed. This suggested a new statistical analysis indicating that (1)
      the size of the insert, the position and the interactions of the insert with the
      genetic backgrounds into which the P-element are inserted have effects on
      lifespan similar to those attributed to overexpression; (2) these effects occur
      without expression of the transfected gene; and (3) effects of interactions with
      backgrounds and effects of positions are as large as responses to six generations
      of strong directional artificial selection. Reports of effects of overexpression
      of transfected genes on lifespan in Drosophila melanogaster may be experimental
      artefacts. Credible experiments on the phenotypic effects of transgenesis need
      proper controls for the effects of insert size and position and should estimate
      the magnitudes of interactions of treatment with genetic backgrounds.

PMID- 9023989
TI  - Substitution rate variation in closely related rodent species.
AB  - The existence of evolutionary rate variation has previously been demonstrated
      between different orders, different species and even between different regions of
      the same gene. To examine rate variation between closely related species of
      rodents we have sequenced the adenine phosphorybosyltransferase (APRT) gene from
      Mus spicilegus, Mus pahari, Mastomys hildebrandtii, Stochomys longicaudatus and
      Gerbillus campestris and compared these sequences with the previously published
      Mus musculus, Rattus norvegicus and Mesocricetus auratus APRT sequences. The
      alignment of these eight rodent APRT sequences reveals two large insertions
      within the introns: an insertion with sequence similar to a B1 repetitive element
      is found within Mastomys and an insertion with sequence similar to a B2
      repetitive element is found within M. pahari. A phylogeny for the rodent APRTs
      agrees with the previously published rodent phylogeny based on other molecular
      and morphological data. The relative rate test which is often used to test for
      variation in rates of evolution in different lineages is shown here to be
      sensitive to the choice of outgroup and therefore should be used with great
      caution. This sensitivity is detectable only with closely related species and
      results from the prevalence of homoplastic substitutions. Rate variation is
      demonstrated within the APRT exons and introns and between the rodent species
      (with the most significant difference being a rate difference in M. spicilegus).
      In addition, some third codon positions are shown to be more prone to
      substitution than others. This clearly demonstrates that even between very
      closely related species there is ample evidence of major differences in rates of
      evolution among species, among regions of the gene and among different positions
      within the gene. We also demonstrate that standard methods of analysis might not
      detect this variation.

PMID- 9023990
TI  - Randomly amplified polymorphic DNA (RAPD) analysis of Atlantic Coast striped
      bass.
AB  - Atlantic Coast striped bass exhibit exceptionally low levels of genetic
      variation. The ability of the randomly amplified polymorphic DNA (RAPD) method to
      uncover genetic variation in this highly conserved species was investigated.
      Sufficient levels of variation were detected to allow a population genetic
      analysis of the four migratory populations of Atlantic Coast striped bass.
      Lynch's analogue of Wright's FST (F'ST) suggests that Atlantic Coast striped bass
      are genetically subdivided (F'ST for pooled Atlantic samples = 0.44). Significant
      heterogeneity was detected in the frequencies of 32 per cent of surveyed RAPD
      markers. A modification of Slatkin's conditional average frequency method
      suggests that gene flow is present among the sampled Atlantic Coast striped bass.
      Results of the RAPD analysis suggest that gene flow is sufficient to prevent
      fixation of alternate genetic markers, but not sufficient to prevent the
      development of significant divergence in frequencies of these markers.

PMID- 9023991
TI  - Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases.
AB  - Bafilomycins and concanamycins, two groups of the plecomacrolide-defined class of
      macrolide antibiotics, have recently been recognized as important tools for
      studying the physiological role of vacuolar-type, proton-translocating ATPases (V
      ATPases) and ATPases with phosphorylated states (P-ATPases) in animal and plant
      cells as well as in yeast, fungi and bacteria. The following review will give an
      account of the classification and function of these antibiotics.

PMID- 9023992
TI  - Intraoperative sarcomere length measurements reveal differential design of human
      wrist extensor muscles.
AB  - The design of the wrist extensor muscles was studied using a combination of
      intraoperative laser diffraction and biomechanical modelling of data obtained
      from human patients and previously published data. Intraoperatively, the change
      in sarcomere length per degree joint angle rotation (i.e. dSL/d omega) was
      measured as the wrist was moved from neutral to full flexion in both the extensor
      carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) muscles.
      Sarcomere length change per degree rotation was approximately twice as great for
      the ECRB compared with the ECRL muscle (9.06 +/- 1.06 versus 4.69 +/- 1.20 nm
      degree-1, mean +/- S.E.M., N = 7). Muscle fibre length and wrist extensor moment
      arms were obtained from published data and dSL/d omega calculated. The
      experimental values for dSL/d omega were extremely close to the calculated
      values. These data demonstrate that architectural differences between the ECRB
      and ECRL are accentuated by differences between their wrist extensor moment arms.
      This differential design may permit the extensor muscles, as a group, to generate
      high force over a wider range of velocities than would be possible with a single
      muscle or it may permit conservation of mass such that the two muscles together
      can generate approximately the same force and excursion as a single muscle but
      with approximately 30% less mass.

PMID- 9023993
TI  - cDNA cloning of myosin heavy chain isoforms from carp fast skeletal muscle and
      their gene expression associated with temperature acclimation.
AB  - We have isolated cDNA clones encoding fast skeletal muscle myosin heavy chains of
      carp acclimated to 10, 20 and 30 degrees C for over 5 weeks. All clones covered
      at least the full length of L-meromyosin, the C-terminal part of the myosin
      molecule. Nucleotide sequence analysis on cDNA clones showed three types of 3'
      untranslated sequences, demonstrating that carp expresses at least three myosin
      heavy chain isoforms in fast skeletal muscle in an acclimation-temperature
      dependent manner. cDNAs were identified which were the predominant types
      expressed in 10 degrees C- and 30 degrees C-acclimated fish, as well as an
      intermediate type present at all acclimation temperatures. Northern blot analysis
      using probes of three kinds of DNA fragments from the 3' untranslated region of
      carp acclimated to 10, 20 and 30 degrees C further confirmed the presence of
      acclimation-temperature-specific isoforms. In addition, it was found that mRNA
      levels of three isoforms were altered in an acclimation-temperature-dependent
      manner. When the deduced amino acid sequences of three types of carp L-meromyosin
      were compared with those of homoiotherms, the 30 degrees C-acclimated type was
      more similar to those of homoiotherms than was the 10 degrees C-acclimated type.

PMID- 9023994
TI  - Locomotor design of dolphin vertebral columns: bending mechanics and morphology
      of Delphinus delphis.
AB  - The primary skeletal structure used by dolphins to generate the dorsoventral
      bending characteristic of cetacean swimming is the vertebral column. In the
      vertebral column of the saddleback dolphin Delphinus delphis, we characterize the
      static and dynamic mechanical properties of the intervertebral joints, describe
      regional variation and dorsoventral asymmetries in mechanical performance, and
      investigate how the mechanical properties are correlated with vertebral
      morphologies. Using a bending machine that applies an external load (N m) to a
      single intervertebral segment, we measured the resulting angular deformation
      (rad) of the segment in both dorsal extension and ventral flexion. Intervertebral
      segments from the thoracic, lumbar and caudal regions of the vertebral column
      were tested from five individuals. Using quasi-static bending tests, we measured
      the initial (low-strain) bending stiffness (N m rad-1) as a function of segment
      position, direction of bending (extension and flexion) and sequential cutting of
      intervertebral ligaments. We found that initial bending stiffness was
      significantly greater in the lumbar region than in adjacent thoracic and caudal
      regions, and all joints were stiffer in extension than is predicted (r2 = 0.554)
      by the length and width of the intervertebral disc and the length of the cranial
      vertebral body in the segment. Stiffness in flexion is predicted (r2 = 0.400) by
      the width of the nucleus pulposus, the length of the caudal vertebral body in the
      segment and the height of the transverse processes from the ventral surface of
      the vertebral body. We also performed dynamic bending tests on intervertebral
      segments from the lumbo-caudal joint and the joint between caudal vertebrae 7 and
      8. Dynamic bending stiffness (N m rad-1) increases with increasing bending
      amplitude and is independent of bending frequency. Damping coefficient (kg m2 rad
      2 s-1) decreases with increasing bending amplitude and frequency. Resilience (%
      energy return) increases from approximately 20% at low bending amplitudes (+/-0.6
      degree) to approximately 50% at high bending amplitudes (+/-2.9 degrees). Based
      on these findings, the dolphin's vertebral column has the mechanical capacity to
      help control the body's locomotor reconfigurations, to store elastic energy and
      to dampen oscillations.

PMID- 9023995
TI  - Prey ingestion revealed by oesophagus and stomach temperature recordings in
      cormorants.
AB  - We examined the accuracy of both stomach and oesophagus temperature sensors
      deployed on captive Brandt's cormorants-for determination of the mass of food
      ingested and the number of prey items swallowed. The oesophageal temperature
      sensor was a better detector of all feeding events, including that of small prey
      which were missed by the stomach sensor. Adapted to free-ranging animals (and
      coupled to data loggers for recording seawater temperature), oesophagus
      temperature recorders, in conjunction with both recordings of energy expenditure
      (e.g. doubly labelled water, heart rate) and determination of position (e.g.
      Argos transmitter, time/depth recorder), should provide further important
      insights into the foraging success of marine endotherms.

PMID- 9023996
TI  - Characterisation of the binding of leukotriene B4 to macrophages of the rainbow
      trout Oncorhynchus mykiss.
AB  - The binding of leukotriene B4 (LTB4) to macrophages from the head kidney of the
      rainbow trout Oncorhynchus mykiss was measured. Binding of [3H]LTB4 achieved a
      steady state after approximately 30 min of incubation and was 30% reversible in
      the presence of a minimum of 1000-fold excess of LTB4. Scatchard analysis of the
      kinetics of LTB4 binding over a range of [3H]LTB4 concentrations indicated the
      existence of only a single class of receptor with a dissociation constant, KD, of
      0.14 nmol l-1 and a maximum receptor density, Bmax, of approximately 17,800 sites
      per macrophage. The LTB4 receptor antagonist LY223982 was ineffective in
      inhibiting the binding of [3H]LTB4 to trout macrophages, although another
      receptor antagonist, LTB4-dimethylamide, displaced a maximum of 25% of the total
      binding. LTB5 was equally effective as LTB4 at displacing [3H]LTB4, while other
      eicosanoids tested were without significant effect. It is suggested that the
      putative receptors for LTB4 on trout macrophages are similar to the high-affinity
      receptors for this compound reported to occur on mammalian granulocytes, although
      any structural similarities of the binding sites await further investigation.

PMID- 9023997
TI  - Monoclonal antibody detection of Pseudomonas spp. in refrigerated meat by an
      indirect ELISA.
AB  - Monoclonal antibodies generated against live cells of Pseudomonas fluorescens
      have been used in an indirect ELISA format for the detection of Pseudomonas spp.
      in refrigerated meat. The detection threshold for the ELISA assay developed in
      this work was 10(4) cfu cm-2.

PMID- 9023998
TI  - Thermal resistance of Enterobacter sakazakii in reconstituted dried-infant
      formula.
AB  - Enterobacter sakazakii, designated a unique species in 1980, has been implicated
      in a rare but severe form of neonatal meningitis, with dried-infant formula being
      implicated as the mode of transmission. The high mortality rate (40-80%) and the
      lack of information about this organism led to a study of the heat resistance of
      Ent. sakazakii in reconstituted dried-infant formula. Ten Canadian Ent. sakazakii
      strains (5 clinical and 5 food isolates) were used to determine the heat
      resistance of this organism at 52, 54, 56, 58 and 60 degrees C in reconstituted
      dried-infant formula. D-values of 54.8, 23.7, 10.3, 4.2 and 2.5 min were obtained
      for each temperature, respectively. The overall calculated z-value was 5.82
      degrees C. In a comparison of the D-values of several members of the
      Enterobacteriaceae in dairy products, Ent. sakazakii appeared to be one of the
      most thermotolerant organisms. The importance of process control during
      manufacture and the use of aseptic procedures during the preparation, use and
      storage of dried-infant formula is discussed.

PMID- 9023999
TI  - Lactic acid bacteria: hydrophobicity and strength of attachment to meat surfaces.
AB  - The hydrophobicity and strength of attachment of several lactic acid bacteria
      with antimicrobial activity were studied. Hydrophobicity was determined by
      bacterial adherence to hydrocarbons (BATH; octane or xylene), adhesion to
      nitrocellulose filters (NCF), salt aggregation test (SAT) and adherence to phenyl
      Sepharose beads (PSB). The relative hydrophobicity of lactic acid bacteria
      depended markedly on the method used. No correlation between either SAT or BATH
      (octane) and strength of attachment (Sr value) existed. However, a significant
      relationship between strength of attachment and BATH (xylene), NCF and PSB,
      respectively, was observed, showing the highest correlation coefficient (r =
      0.778) for BATH (xylene).

PMID- 9024000
TI  - New media for detection and counting of Clostridia in foods.
AB  - The growth of pure cultures of Clostridium perfringens (ATCC 12922) and Cl.
      sporogenes (PA 3679) in five non-selective media, fluid thioglycollate medium
      (FTM), rapid perfringens medium (RPM), Columbia broth Malthus (CBM), reinforced
      clostridial medium (RCM) and lactose sulphite (LS), was monitored using
      conductance measurements with a Malthus analyser. Only FTM and CBM gave useful
      results. The correlation of log10 plate counts on blood agar of the pure strain
      of Cl. sporogenes with detection times in FTM was highly significant (r = 0.96, n
      = 73), and with detection times in CBM less so (r = -0.909, n = 33). The
      correlation of log10 counts on tryptose sulphite neomycin medium (TSN) of wild
      strains of Cl. sporogenes and Cl. perfringens with detection times with FTM in
      meat was also highly significant (r = 0.933, n = 54).

PMID- 9024001
TI  - A rapid plate assay for screening L-asparaginase producing micro-organisms.
AB  - A pH and dye-based fast procedure for screening L-asparaginase producing micro
      organisms is reported. The procedure is suitable for bacterial and fungal
      screening. The results are obtained within 24 and 48 h for bacteria and fungi,
      respectively. The results correlate with quantitative estimations in culture
      broths.

PMID- 9024002
TI  - The effect of temperature on the growth of strains of Kloeckera apiculata and
      Saccharomyces cerevisiae in apple juice fermentation.
AB  - The influence of temperature (10 degrees C and 25 degrees C) on the survival and
      growth of Saccharomyces cerevisiae and Kloeckera apiculata was examined in mixed
      and pure cultures during fermentation in apple juice. The growth reached by S.
      cerevisiae did not seem to be affected by temperature and the presence of K.
      apiculata. However, the growth and survival of K. apiculata, both in single and
      mixed cultures, were substantially enhanced at 10 degrees C. The highest amount
      of ethyl acetate was produced by K. apiculata in pure culture at 10 degrees C.
      Nevertheless, this concentration was lowest when both yeasts were fermented
      together at 10 degrees C and 25 degrees C.

PMID- 9024003
TI  - PCR detection of sequences similar to the AS-48 structural gene in bacteriocin
      producing enterococci.
AB  - Three oligonucleotide primers, specific for the structural gene of antimicrobial
      peptide AS-48, were used to study the distribution of sequences similar to this
      gene in 15 independently isolated bacteriocin-producing Enterococcus strains by
      semi-nested PCR. Eight of 10 Ent. faecalis strains and three of five Ent. faecium
      strains gave a positive result in both reactions of the semi-nested PCR. These
      findings indicate that bacteriocins produced by many enterococcal strains are
      very closely related or even identical to peptide AS-48.

PMID- 9024004
TI  - Glucosyltransferase activity of commercial juice-processing enzyme preparations.
AB  - Of various commercial enzyme preparations examined, Cytolase M102 was found to
      contain the highest glucosyltransferase activity (55 U ml-1). It rapidly
      converted maltose to panose (Glc alpha-->6 Glc alpha l-->4 Glc) with a Vmax value
      of 5.8 mmol l-1 min-1 at 50 degrees C in 0.05 mol l-1 sodium acetate buffer (pH
      4.4). The Km value of the enzyme for maltose was 750 mmol l-1. Yields of panose
      and glucose after 45 min of reaction, for example, were 47.2% and 52.8%,
      respectively, on the basis of the amount of maltose consumed.

PMID- 9024005
TI  - Optimization of the detection of bacteriophages induced from Listeria sp.
AB  - It is necessary to isolate new phages in order to improve the rate of typeability
      of Listeria monocytogenes strains. We propose a method which increases the
      detection of induced phages in the presence of inhibitory substances synthesized
      or liberated by the cells during phage production. Of the 29 phages isolated, 11
      (38%) were detected by the spot-on-the-lawn technique and 18 (62%) were revealed
      by the soft-agar technique. To increase the rate of phage detection, both
      techniques appear useful. Listeria cultures were subjected to phage typing
      procedures utilizing these newly isolated phages and the French International set
      of phages. It appears that the newly isolated phages are good tools for the
      differentiation of Listeria strains. Among them, one phage seems to be
      complementary to the French International set.

PMID- 9024006
TI  - Isolation and characterization of a novel catalase-negative, urease-positive
      Campylobacter from cattle faeces.
AB  - Forty-four strains of a phenotypically unique Campylobacter were isolated from
      the faeces of 26 of 45 cows in a single herd. Isolation involved enrichment and
      membrane filtration onto blood agar or plating onto cefoperazone amphotericin
      teicoplanin agar. The strains exhibited phenotypic characteristics typical for
      Campylobacter species. However, they were unusual in that they produced urease
      and copious H2S in triple sugar iron (TSI) medium, but did not produce catalase.
      They did not grow aerobically. None of the strains grew on modified cefoperazone
      charcoal deoxycholate agar (mCCDA). Macrorestriction profiles of chromosomal DNA
      were prepared for 15 strains using pulsed-field gel electrophoresis (PFGE).
      Twelve of 15 profiles were identical and all appeared to be closely related.
      These catalase-negative, urease-positive campylobacters (CNUPC) represent a group
      not previously reported. Their sensitivity to antibiotics normally used in
      selective media for campylobacters might explain why they have not previously
      been encountered. Their ecological significance and importance with respect to
      human and animal disease remain to be assessed.

PMID- 9024007
TI  - A case of foodborne listeriosis in Sweden.
AB  - A 70-year-old woman fell seriously ill overnight with meningitis and was admitted
      to hospital. Cerebrospinal fluid culture yielded Listeria monocytogenes. One of
      the first problems in solving a human case of listeriosis suspected to be
      foodborne is to find the foods likely to have been transmitting L. monocytogenes.
      Two enrichment procedures and a direct plating procedure were used for isolation
      of the bacteria from different food items collected from the patient's
      refrigerator, local retail store and producer. Samples of vacuum-packed products
      of sliced pork brawn, sliced cooked medwurst and berliner wurst of the same brand
      harboured L. monocytogenes. Serotyping and restriction enzyme analysis (REA) with
      pulsed-field gel electrophoresis (PFGE) were used to characterize and compare 41
      isolates, including the human strain. At least three clones were present in the
      foods investigated, and one of these was identical to the human clone. This clone
      was present in samples of medwurst from the patient's refrigerator and the local
      retail store. This is, to our knowledge, the first proven foodborne case of
      listeriosis reported in Sweden.

PMID- 9024008
TI  - Complexities overlooked: things may not be what they seem.

PMID- 9024009
TI  - Intrathecal morphine for coronary artery bypass grafting and early extubation.
AB  - Aggressive control of pain during the immediate postoperative period after
      cardiac surgery with early tracheal extubation may decrease morbidity and
      mortality. This prospective, randomized, double-blinded, placebo-controlled
      clinical study examined the use of intrathecal morphine in patients undergoing
      cardiac surgery and its influence on early tracheal extubation and postoperative
      analgesic requirements. Patients were randomized to receive either 10
      micrograms/kg of intrathecal morphine (n = 19) or intrathecal placebo (n = 21).
      Perioperative anesthetic management was standardized (intravenous (IV) fentanyl,
      20 micrograms/kg, and IV midazolam, 10 mg) and included postoperative patient
      controlled morphine analgesia. Of the patients who were tracheally extubated
      during the immediate postoperative period, the mean time from intensive care unit
      arrival to extubation was significantly prolonged in patients who received
      intrathecal morphine (10.9 h) when compared to patients who received intrathecal
      placebo (7.6 h). Three patients who received intrathecal morphine had extubation
      substantially delayed because of prolonged ventilatory depression. Although mean
      postoperative IV morphine use for 48 h was less in patients who received
      intrathecal morphine (42.8 mg) when compared to patients who received intrathecal
      placebo (55.0 mg), the difference between groups was not statistically
      significant. In conclusion, intrathecal morphine offers promise as a useful
      adjunct in controlling postoperative pain in patients after cardiac surgery.
      However, the optimal dose of intrathecal morphine in this setting, along with the
      optimal intraoperative baseline anesthetic that will provide significant
      analgesia, yet not delay extubation in the immediate postoperative period,
      remains to be elucidated.

PMID- 9024010
TI  - Immediate tracheal extubation after liver transplantation: experience of two
      transplant centers.
AB  - Early tracheal extubation has been safely performed after large operative
      procedures, questioning the need for routine postoperative ventilation. Because
      immediate postoperative tracheal extubation of liver transplantation patients has
      not been previously reported, we performed preliminary studies at two
      institutions to evaluate potential risk and cost benefit. At the University of
      Colorado (UC), extubation criteria were derived from the retrospective analysis
      of patients who were ventilated less than 8 h and experienced an intensive care
      unit stay less than 48 h in 1994. Preoperative criteria for age, severity of
      illness, and absence of encephalopathy and coexistent disease were used in a
      subsequent prospective study in 1995. Donor graft function, blood use,
      hemodynamic stability, and alveolar-arterial oxygen gradient served as
      intraoperative criteria. Cost of intensive care services was compared for the
      1994 ventilated patients and the 1995 patients whose tracheas were extubated
      immediately postoperatively. At the second institution, University of California
      at San Francisco (UCSF), patients were tracheally extubated immediately
      postoperatively, based on clinical judgment by the anesthesiologist. A
      retrospective analysis was then completed. Sixteen of 67 patients at UC and 25 of
      106 patients at UCSF were tracheally extubated. There were no reintubations at
      UC, while 2 of 25 patients at UCSF required reintubation. Prior encephalopathy,
      poor donor liver function, and an increased alveolar-arterial oxygen gradient
      were present in the patients who suffered perioperative respiratory failure.
      Seventeen of 25 patients at UCSF did not have all criteria used at UC but did not
      require reintubation. Wider limits on age and severity of illness did not
      preclude successful extubation. Cost analysis at UC showed a significant
      reduction in intensive care unit services and associated cost for extubated
      patients. We conclude that immediate postoperative tracheal extubation of
      selected liver transplantation patients is safe and cost effective.

PMID- 9024011
TI  - Response to clamping of the inferior vena cava as a factor for predicting
      postreperfusion syndrome during liver transplantation.
AB  - Postreperfusion syndrome (PRS) is an important cause of hemodynamic deterioration
      during orthotopic liver transplantation (OLT). We retrospectively studied 94
      patients who had undergone OLT in an effort to establish whether the hemodynamic
      response to clamping of the inferior vena cava (IVC) could be used to predict
      hemodynamic behavior on reperfusion of the grafted liver. PRS was defined as a
      decrease in the mean arterial pressure of more than 30% below the baseline value
      for more than 1 min during the first 5 min after reperfusion of the graft. The
      patients were divided into two groups: those who developed PRS (PRS group) and
      those who did not (non-PRS group). We analyzed hemodynamic response before
      (dissection stage) and after (anhepatic stage) clamping of the IVC. Based on
      multivariate analysis methods (logistic regression), the percentage of change in
      the vascular resistance index from before clamping to after clamping of the IVC
      was an indicator of the risk of developing PRS, with an adjusted odds ratio of
      1.04 for each unit of change (ENTER method, P = 0.01). In the non-PRS group,
      clamping of the IVC was followed by a 47.1% decrease in the cardiac index,
      compared with a 27.9% decrease in the PRS group (P < 0.05). The systemic vascular
      resistance index (SVRI) increased by 49% in the PRS group, as opposed to 85.7% in
      the non-PRS group (P < 0.05). PRS occurred in only 17.5% of patients in whom the
      SVRI increased by more than 50%. We conclude that the integrity of the
      vasoconstrictive response (increase in the peripheral vascular resistance greater
      than 50%) as measured immediately after clamping of the IVC correlates with
      occurrence of PRS.

PMID- 9024012
TI  - Hands-up positioning during asymmetric sternal retraction for internal mammary
      artery harvest: a possible method to reduce brachial plexus injury.
AB  - This study compares the hands-up (HU) with the arms at side (AAS) position to
      determine whether one is beneficial in reducing brachial plexus stress during
      asymmetric sternal retraction. Eighty patients undergoing cardiac surgery were
      assigned to either Group 1 (AAS) or Group 2 (HU). Perioperative neurologic
      evaluations of the brachial plexus were performed and somatosensory evoked
      potentials (SSEPs) were collected during internal mammary artery harvest using
      asymmetric sternal retraction. Demographic data, SSEP changes, and postoperative
      brachial plexus symptoms were compared between groups. SSEP amplitude decreased
      in 95% of all patients during retractor placement with substantial decreases (>
      50%) observed on the left side in 50% of the AAS and 35% of the HU patients.
      Amplitude recovery was normally seen in both groups after asymmetric retractor
      removal. Similar changes were noted, to a lesser degree, on the right side.
      During asymmetric sternal retraction, HU positioning offered minimal benefit in
      reducing brachial plexus stress as measured by SSEP. Three of the seven AAS
      patients who reported brachial plexus symptoms had an ulnar nerve distribution of
      injury. However, none of the four patients with plexus symptoms in the HU group
      had ulnar nerve problems, suggesting that the higher incidence of postoperative
      symptoms observed with AAS positioning may occur from ulnar nerve compression.

PMID- 9024013
TI  - Cloricromene reduces myocardial infarct size in rabbits when administered during
      the early reperfusion period.
AB  - Cloricromene is a coumarin derivative without anticoagulant activities that has
      recently been found to decrease myocardial infarct size after an ischemic
      reperfusion injury. This study seeks to determine when the cardioprotective
      action of cloricromene is exerted in an in vivo rabbit model of ischemic
      reperfusion injury. Forty-nine rabbits subjected to 30 min of coronary occlusion
      and 120 min of reperfusion were randomized into five groups: VEH (n = 11)
      received saline vehicle; IR (n = 9) received an infusion of cloricromene starting
      at the onset of ischemia at 8 micrograms.kg-1.min-1; R(-5)(n = 9) and R(+30)(n =
      9) received an infusion of cloricromene at 8 micrograms.kg-1.min-1 starting 5 min
      before reperfusion and 30 min after reperfusion, respectively; and RB(-5)(n = 11)
      received 300 micrograms/kg bolus of cloricromene 5 min before reperfusion
      followed by an infusion of 8 micrograms.kg-1.min-1. All infusions were continued
      until the end of the reperfusion period. Myocardial infarct size was
      significantly reduced in groups IR, R(-5), and RB(-5). We conclude that
      cloricromene's effective time of action occurs prior to the first 30 min of the
      reperfusion period.

PMID- 9024014
TI  - The effects of desflurane on splanchnic hemodynamics and oxygenation in the
      anesthetized pig.
AB  - This study was designed to investigate the effects of desflurane on systemic and
      splanchnic hemodynamics, O2 delivery and O2 uptake, tissue oxygenation (as
      monitored by surface PO2 electrodes), and hepatic oxygen-dependent intermediary
      metabolism (hepatic lactate uptake, intestinal lactate production, ketone-body
      ratio) in the pig. We studied 11 anesthetized (i.e., ketamine, flunitrazepam,
      vecuronium) and ventilated domestic pigs (17-23 kg). After instrumentation,
      desflurane was administered randomly at 0.5 minimum alveolar anesthetic
      concentration (MAC) (4.2 vol %) and 1.0 MAC (8.3 vol %). Desflurane caused dose
      dependent decreases in heart rate, mean arterial blood pressure, and cardiac
      output. Hepatic arterial blood flow was not affected at 0.5 MAC but decreased at
      1.0 MAC. In contrast, portal and superior mesenteric arterial blood flow
      decreased at 0.5 MAC but did not show any further significant decrease at 1.0
      MAC. Total hepatic blood flow decreased dose-dependently. Although O2 deliveries
      of whole body, liver, and small intestine were markedly reduced at both
      concentrations, respective O2 uptakes did not change significantly. The decreases
      in O2 deliveries were reflected by moderate disturbances in hepatic and small
      intestinal surface PO2. No evidence for severe tissue hypoxia could be detected.
      Desflurane had no adverse effects on hepatic and small intestinal metabolic
      function. These data indicate that hepatic and small intestinal O2 reserve
      capacity is impaired by desflurane.

PMID- 9024015
TI  - Isoflurane and halothane attenuate endothelium-dependent vasodilation in rat
      coronary microvessels.
AB  - Volatile anesthetics attenuate endothelium-dependent vasodilation but the
      mechanism of attenuation remains controversial. The present study examines the
      mechanism of isoflurane- and halothane-mediated attenuation of endothelium
      dependent vasodilation in Wistar rat coronary microvessels of about 100 microns
      internal diameter. The vessels were studied in vitro in a pressurized (40 mm Hg),
      no-flow state using video microscopy. After preconstriction of the vessels with
      the thromboxane analog U46619 1 microM, concentration response curves to
      acetylcholine (ACh), the calcium ionophore A23187, sodium nitroprusside (SNP), or
      the stable cyclic guanosine monophosphate (cGMP) analog 8-bromo-cGMP (Br-cGMP)
      were obtained in the presence of 0% (control), 1% or 2% isoflurane, or 1% or 2%
      halothane. Isoflurane 1% and 2% significantly attenuated vasodilation to ACh and
      A23187. Isoflurane 2%, but not 1%, attenuated vasodilation to SNP. Vasodilation
      to Br-cGMP was not affected by isoflurane. Halothane attenuated vasodilation to
      ACh, but had no effect on vasodilation to A23187, SNP, or Br-cGMP. We conclude
      that isoflurane attenuates endothelium-dependent vasodilation by impairing at
      least two distinct steps in the nitric oxide (NO)-cGMP pathway, the first being
      between endothelial increase of calcium and smooth muscle guanylate cyclase and
      the second being inhibition of soluble guanylate cyclase activity. These two
      steps appear to have different sensitivities to the effect of isoflurane.
      Halothane has an effect at the endothelial receptor level, but not any distal
      steps in the NO-cGMP pathway.

PMID- 9024016
TI  - Voltage-dependent effects of volatile anesthetics on cardiac sodium current.
AB  - Cardiac dysrhythmias during inhaled anesthesia are well documented and may, in
      part, involve depression of the fast inward Na+ current (INa) during the action
      potential upstroke. In this study, we examined the effects of halothane,
      isoflurane, and sevoflurane at clinically relevant concentrations on INa in
      single ventricular myocytes isolated enzymatically from adult guinea pig hearts.
      INa was recorded using standard whole-cell configuration of the patch clamp
      technique. Halothane at 0.6 mM and 1.2 mM produced significant (P < 0.05)
      depressions of peak INa of 12.3% +/- 1.8% and 24.4% +/- 4.1% (mean +/- SEM, n =
      12), respectively. Isoflurane (0.5 mM, n = 12; 1.0 mM, n = 15) and sevoflurane
      (0.6 mM, n = 14; 1.2 mM, n = 12) were less potent than halothane, decreasing peak
      INa by 4.8% +/- 1.1% and 11.4% +/- 1.4% (isoflurane) and 3.0% +/- 0.7% and 10.7%
      +/- 3.9% (sevoflurane). The depressant effects on INa were reversible in all
      cases. For all anesthetics tested, the degree of block increased at more
      depolarizing potentials. Anesthetics induced significant shifts in the steady
      state inactivation and activation of the channel toward more hyperpolarizing
      potentials. The present findings indicate that volatile anesthetics at clinical
      concentrations decrease the cardiac INa in a dose- and voltage-dependent manner.
      At approximately equianesthetic concentrations, the decrease of INa caused by
      halothane was twice that observed with isoflurane or sevoflurane.

PMID- 9024017
TI  - A comparison of the hemodynamic effects of amrinone and sodium nitroprusside in
      infants after cardiac surgery.
AB  - The phosphodiesterase inhibitor amrinone (AMR) increases cardiac output in
      children after cardiac surgery. In vitro, amrinone has both positive inotropic
      and vasodilatory effects. However the relative contribution of these effects to
      the increases in cardiac output observed clinically is unclear, and it has not
      been demonstrated that amrinone offers a hemodynamic advantage above that of pure
      vasodilators in infants. We compared the hemodynamic effects of AMR and sodium
      nitroprusside (SNP) in 10 infants after cardiac surgery. Cardiac index (CI) was
      measured by thermodilution after SNP administration, titrated to decrease mean
      blood pressure (MBP) by 20%, and then after a 1.5-mg/kg bolus dose of AMR. Each
      patient served as his or her own control. Preload, as measured by left atrial
      pressure and transesophageal echocardiography (in eight patients), was kept
      constant throughout the protocol. Both SNP and AMR caused significant decreases
      in MBP and systemic vascular resistance index (SVRI). However, only AMR resulted
      in a significant increase in CI. The ratio of fractional increase in CI to
      fractional absolute decrease in MBP was significantly greater for AMR than SNP,
      indicating greater efficacy for AMR in the treatment of low cardiac output
      syndrome and suggesting that, in infants after cardiac surgery, AMR has
      clinically relevant positive inotropic effects.

PMID- 9024018
TI  - Parental desire for perioperative information and informed consent: a two-phase
      study.
AB  - The purpose of this investigation was to identify the perioperative anesthetic
      information parents want from the anesthesiologist, and to determine whether the
      provision of detailed anesthetic risk information is associated with increased
      parental anxiety. The investigation consisted of a cross-sectional study followed
      by a randomized controlled trial. In Phase 1, baseline and situational anxiety,
      coping strategy, and temperament were obtained from parents of children
      undergoing surgery (n = 334). A questionnaire examining the desire for
      perioperative information was administered to all parents. In Phase 2, 47 parents
      were randomly assigned to receive either routine anesthetic risk information
      (control) or detailed anesthetic risk information (intervention). The effect of
      the intervention on parental anxiety was assessed over four time points: prior to
      the intervention, immediately after the intervention, day of surgery in the
      holding area, and at separation to the operating room. For Phase 1, the majority
      of parents (> 95%) preferred to have comprehensive information concerning their
      child's perioperative period, including information about all possible
      complications. For selected items, increased parental educational level was
      associated with increased desire for information (P < 0.05). For Phase 2, when
      the intervention group was compared with the control group, there were no
      significant differences in parental anxiety over the four time points [F(1,45) =
      0.6, P = 0.4]. Also, the interaction between time and group assignment was not
      significant [F(3,135) = 1.66, P = 0.18]. We conclude that parents of children
      undergoing surgery desire comprehensive perioperative information. Moreover, when
      provided with highly detailed anesthetic risk information, the parental anxiety
      level did not increase.

PMID- 9024020
TI  - Fentanyl and alfentanil plasma protein binding in preterm and term neonates.
AB  - The effects of gestational age (GA) and plasma protein concentrations on the
      plasma protein binding of fentanyl and alfentanil were studied in preterm and
      term neonates. Binding experiments were performed using split-cell equilibrium
      dialysis. Fentanyl and alfentanil concentrations were measured using specific
      radioimmunoassay, and the proteins albumin and alpha-1-acid glycoprotein (AAG)
      were measured using radial immunodiffusion assays. In the preterm neonates, 77%
      of fentanyl and 65% of alfentanil was bound. In the term neonates, 70% of
      fentanyl and 79% of alfentanil was bound. The binding ratio of alfentanil showed
      a positive correlation with gestational age and AAG concentration. The binding
      ratio of fentanyl showed a weak, negative correlation with gestational age. These
      data indicate that fentanyl and alfentanil are not interchangeable at the GA
      studied because of age-related changes in protein binding.

PMID- 9024019
TI  - Recovery from doxacurium infusion administered to produce immobility for more
      than four days in pediatric patients in the intensive care unit.
AB  - Doxacurium was administered by titrated infusion to 14 pediatric patients for 4.7
      12.3 days after laryngotracheal reconstruction to produce minimum spontaneous
      movement and less than five posttetanic movements of the first toe after
      stimulation of the posterior tibial nerve. Recovery was documented by stimulation
      of the ulnar nerve with 2 Hz for 2 s (train-of-four [TOF]) at intervals of 1 min
      and measurement of the ratio of the fourth to the first response (TOF ratio) at
      the adductor pollicis. During spontaneous recovery, the TOF ratio was between 0.4
      and 0.7 for 0.6-3.3 h, mean (SEM) 2.2 (0.31) h. The TOF ratio equaled 1 between
      4.7 and 23.0 h, mean (SEM) 11.0 (2.1) h after termination of doxacurium infusion.
      In six of the patients, weakness and decreased coordination were noted for a few
      days to weeks postoperatively. There were no complications related to impairment
      of upper airway function or ventilation in those patients who had recovery of
      neuromuscular transmission to the extent of TOF ratio equal to 1 prior to
      extubation or in those patients in whom weakness or lack of coordination was
      noted after tracheal extubation.

PMID- 9024021
TI  - What happens after discharge? Return hospital visits after ambulatory surgery.
AB  - The purpose of this study was to examine the frequency of return hospital visits
      after ambulatory surgery discharge and to identify any predictor variables for
      its occurrence. A retrospective review of hospital records for all patients
      returning to the same hospital within 30 days after ambulatory surgery was
      conducted. Data on return hospital visits that resulted in rehospitalization (as
      an inpatient or to the ambulatory surgery unit [ASU]) or treatment as an
      outpatient in the emergency room were recorded. A total of 6243 patients
      underwent ambulatory surgery over 12 consecutive months and 187 returned to the
      same hospital of which 1.3% were for complications. Of all the returns, 54%
      returned to the emergency room (ER) and 46% were rehospitalized as inpatients or
      to ASU. To identify factors associated with an increased likelihood of return,
      two case controls for each return visit were obtained from medical records of
      ambulatory surgical patients operated on during the same time period. Results of
      the multivariate analysis on the matched case controls identified urology as the
      only significant surgical service that predicted returns. (Odds ratio 27.87;
      confidence interval [CI] 3.78-74.86; P = 0.0002). A separate analysis of the most
      common ASU procedures performed identified two surgical procedures that predicted
      hospital return as compared with overall ambulatory surgery population: patients
      undergoing varicocelectomy and hydrocelectomy procedures were 8.3 times more
      likely to return (CI 2.090-23.75; P = 0.0042); patients undergoing dilation and
      curettage were three times as likely to return (CI 1.78-5.55; P = 0.0002).
      Bleeding was the most common reason for all hospital returns (41.5%), with 76.5%
      of these patients treated and discharged through the ER. The increased likelihood
      of return visits after urology procedures warrants further evaluation. As
      patients with bleeding were most likely to return to the ER and discharged, more
      effective pre- and postprocedure patient education may further reduce this
      occurrence. Better informing patients regarding the prognosis of bleeding, and
      advising them of medical alternatives, could reduce inappropriate patient returns
      to the ER.

PMID- 9024022
TI  - Intravenous dolasetron for the prevention of postoperative nausea and vomiting
      after outpatient laparoscopic gynecologic surgery.
AB  - The newer 5-hydroxytryptamine type 3 (5-HT3) antagonists are sometimes considered
      for routine prophylaxis of postoperative nausea and vomiting (PONV) in high-risk
      patients. This multicenter, randomized, double-blind, placebo-controlled study
      compared the efficacy and safety of three single intravenous (IV) doses of
      dolasetron mesylate salt (12.5, 25, or 50 mg) for the prevention of PONV in 635
      females undergoing outpatient laparoscopic gynecologic surgery. Antiemetic
      efficacy was evaluated over a 24-h postoperative period by recording the number
      and timing of emetic episodes; effects on nausea were evaluated by a visual
      analog scale (VAS). The proportion of complete responders (no emetic episodes and
      no escape medication in 24 h) was significantly higher with each dolasetron
      mesylate dose (> 50% for each dose; P < or = 0.0003) than with placebo (30.6%).
      Fewer patients given dolasetron required or requested escape antiemetic
      medication compared with placebo (P < 0.0003). Dolasetron-treated patients had
      significantly (P < 0.0357) lower median postdose maximum nausea VAS scores
      compared with placebo-treated patients. Patient satisfaction with dolasetron was
      high and, overall, was significantly (P = 0.0131) greater than that with placebo.
      Dolasetron was an effective and well tolerated preventive treatment for PONV
      resulting from laparoscopic gynecologic surgery.

PMID- 9024023
TI  - The effect of timing of ondansetron administration in outpatients undergoing
      otolaryngologic surgery.
AB  - A randomized, double-blind, placebo-controlled study was designed to compare the
      relative efficacy of prophylactic ondansetron, 4 mg intravenously (IV), when
      administered before induction of anesthesia or at the end of surgery to an
      outpatient population at high risk of developing postoperative nausea and
      vomiting (PONV). Patients undergoing otolaryngologic surgery were randomly
      assigned to one of three different treatment groups: Group 1 (placebo) received
      saline 5 mL prior to induction of anesthesia and again at the end of surgery;
      Group II received ondansetron 4 mg in 5 mL prior to induction of anesthesia and
      saline 5 mL at the end of surgery; and Group III received saline 5 mL prior to
      induction of anesthesia and ondansetron 4 mg at the end of surgery. All patients
      received the same general anesthetic technique. A standardized regimen of rescue
      antiemetics was administered in the recovery room to patients with > or = 2
      emetic episodes or at the patients request for persistent nausea. Episodes of
      nausea and vomiting, as well as the need for rescue antiemetics, were recorded
      for 24 h after the operation. The incidences of nausea and emesis in the recovery
      room after prophylactic ondansetron, 4 mg IV, administered either before
      induction (68% and 20%, respectively) or at the end of surgery (60% and 4%,
      respectively) were not significantly decreased compared to the placebo control
      group (80% and 12%, respectively). However, when ondansetron was administered at
      the end of the operation, it significantly reduced the need for rescue
      antiemetics in the recovery room (36% vs 64% in the control group). The
      postanesthesia care unit and hospital discharge times were similar in all three
      study groups. One patients in Group II and one patient in Group III were
      hospitalized because of intractable symptoms related to PONV. After discharge
      from the ambulatory surgery unit, the incidence of nausea, vomiting, and the need
      for rescue antiemetic drugs were similar in all three treatment groups. In
      conclusion, ondansetron (4 mg IV) was more effective in reducing the need for
      rescue antiemetics in the recovery room when administered at the end versus prior
      to the start of otolaryngologic surgery. Therefore, when ondansetron is used for
      antiemetic prophylaxis in outpatients undergoing otolaryngologic procedures, it
      should be administered at the end of the operation rather than prior to induction
      of anesthesia.

PMID- 9024024
TI  - The direction of the Whitacre needle aperture affects the extent and duration of
      isobaric spinal anesthesia.
AB  - The use of Whitacre spinal needles results in directional flow out of the needle
      aperture, diverting local anesthetic from the longitudinal axis of the needle.
      Thus, a change in orientation of the needle aperture would be expected to result
      in a different local anesthetic distribution in the subarachnoid space. We
      studied 40 outpatients undergoing elective knee arthroscopy under spinal
      anesthesia with 60 mg plain lidocaine 2% in a prospective, double-blinded manner.
      Patients were randomly assigned to either Group I (needle aperture oriented in a
      cephalad direction throughout intrathecal injection) or Group II (aperture
      directed caudally). Onset and offset of sensory and motor block were analyzed at
      frequent intervals. Times to completion of ambulatory milestones, including
      discharge, were recorded. Group I was characterized by a higher sensory level (T
      3.4 +/- 1.3 vs T 6.6 +/- 2.8, P < 0.001). Group I had significantly shorter
      duration of lumbar sensory anesthesia (149.2 +/- 30.6 min vs 177.8 +/- 23.5 min,
      P < 0.01) and motor blockade (117.6 +/- 26.1 min vs 150.0 +/- 22.8 min, P <
      0.001). Mean time to outpatient discharge was approximately 32 min shorter in
      Group I. The orientation of the Whitacre needle aperture exerts a major influence
      on sensory level, as well as the duration of isobaric lidocaine spinal
      anesthesia.

PMID- 9024025
TI  - Acupressure versus intravenous metoclopramide to prevent nausea and vomiting
      during spinal anesthesia for cesarean section.
AB  - Nausea and vomiting occur frequently during cesarean section under spinal
      anesthesia. Metoclopramide reduces intraoperative nausea and vomiting, but not
      without potential side effects. Acupressure, a noninvasive variation of
      acupuncture that involves constant pressure on the wrist, has been suggested as
      an alternative method to prevent nausea and vomiting. The aim of this study was
      to compare acupressure and intravenous (IV) metoclopramide for the prevention of
      nausea and vomiting during elective cesarean section under spinal anesthesia.
      Seventy-five patients were studied in a randomized, prospective, double-blind
      comparative trial. Group I patients received acupressure bands + 2 mLIV saline,
      Group II patients received placebo wrist bands + 10 mg IV metoclopramide, and
      Group III patients received placebo wrist bands + 2 mL IV saline. Patients who
      received either acupressure or metoclopramide prior to initiation of spinal
      anesthesia for cesarean section had much less nausea than patients in the placebo
      group. Acupressure is an effective, non-pharmacologic method to reduce
      intraoperative nausea during elective cesarean section in the awake patient.

PMID- 9024026
TI  - Intrathecal sufentanil for labor analgesia: do sensory changes predict better
      analgesia and greater hypotension?
AB  - Sensory changes and hypotension occur after intrathecal sufentanil (ITS) is given
      during labor. The goal of this study was to determine whether sensory changes are
      predictive of hemodynamic changes or duration of pain relief. We also examined
      whether sensory and hemodynamic changes relate to the concentration of ITS
      administered. Forty-five ASA physical status I and II women in active labor were
      randomly assigned to receive 10 micrograms ITS diluted in either 1, 2, or 3 mL of
      normal saline (15 in each group). An observer blinded to treatment recorded
      verbal pain scores, blood pressure, and sensory changes to light touch, pinprick,
      and cold at frequent intervals. Excellent analgesia was obtained in 42 of 45
      patients. There were no differences among the groups with respect to the number
      of patients with sensory changes, the duration of analgesia or sensory changes,
      the quality of analgesia, or the severity of hypotension. The groups were
      therefore combined for further analyses. Among this combined group, the duration
      of analgesia was 99 +/- 7 min (mean +/- SE). Cold, pinprick, and light touch
      sensation were decreased in 66%, 50%, and 33% of patients, respectively. Motor
      block was absent in all patients. The duration and quality of analgesia were
      similar in subjects with and without sensory changes. Systolic blood pressure
      decreased 23 +/- 2 mm Hg (P < 0.05) during the first 30 min after ITS, and six
      patients were given ephedrine. The magnitude of blood pressure change was not
      affected by the diluent volume or the presence of sensory changes. Because
      sensory changes were not predictive of the duration or quality of analgesia or
      the degree of hemodynamic change, we conclude that analgesia with ITS is
      predominantly mediated via spinal cord opioid receptors rather than by a local
      anesthetic-type conduction blockade.

PMID- 9024027
TI  - Extended duration of action of rocuronium in postpartum patients.
AB  - We studied the time course of action of a single bolus of 600 micrograms/kg
      rocuronium given during anesthesia with propofol, fentanyl, and nitrous oxide was
      studied in 12 nonpregnant and 12 postpartum patients. Neuromuscular effects were
      quantified by recording the indirectly evoked twitch response of the adductor
      pollicis muscle after ulnar nerve stimulation. In all patients, the trachea was
      intubated 60 s after administration of rocuronium. Onset time was similar in both
      groups (nonpregnant: 91 +/- 28 s vs. postpartum: 95 +/- 30 s), with the time to
      25% twitch recovery being significantly longer (P < 0.001) in the postpartum
      patients (31.1 +/- 3.6 min) compared with the nonpregnant group (24.9 +/- 4.0
      min). The time required for recovery from 25% to 75% of the control twitch
      response after reversal with neostigmine and atropine was significantly longer (P
      = 0.003) in postpartum (4.8 +/- 0.9 min) than in nonpregnant patients (3.2 +/-
      0.6 min). These data suggest that pregnancy-induced changes result in prolonged
      effects of rocuronium in postpartum patients.

PMID- 9024028
TI  - RB 101, a purported pro drug inhibitor of enkephalin metabolism, is
      antinociceptive in pregnant mice.
AB  - In an earlier study, we demonstrated the enhancement of pregnancy-induced
      analgesia with an inhibitor of endogenous enkephalin metabolism. The purpose of
      the present study was to evaluate the antinociceptive effect of another inhibitor
      of enkephalin metabolism, RB 101, on pregnant mice. Further, since other studies
      have shown RB 101 to be free of opioid side effects, we examined its effect on
      respiratory rate. Analgesia was assessed using the hot plate test, and
      respiratory rate was measured by recording the output from an end-tidal carbon
      dioxide detector. In pregnant mice, experiments were conducted on Day 17 or Day
      18 of pregnancy; mice usually deliver on Day 19. For the hot plate test, animals
      were tested in the following groups: Group 1, RB 101 150 mg/kg (n = 15); Group 2,
      RB 101 50 mg/kg (n = 15); Group 3, RB 101 vehicle (n = 15); Group 4, morphine 5
      mg/kg (n = 14); and Group 5, RB 101 150 mg/kg + naloxone 5 mg/kg (n = 10). The
      test was repeated on the second day after delivery in animals in Groups 1 and 3
      (given RB 101 150 mg/kg and RB 101 vehicle, respectively). RB 101 150 mg/kg and
      morphine 5 mg/kg were significantly different (mean percentage of maximum
      possible effect 30.0 and 37.7, respectively, at 30 min and 41.6 and 32.6,
      respectively, at 60 min) in their antinociceptive effect in pregnant animals from
      all other groups. Naloxone, when coadministered with RB 101, prevented the
      development of antinociception. RB 101 150 mg/kg was not antinociceptive after
      delivery. Depression of respiratory rate was tested in a separate set of animals
      in the following groups: Group 1, RB 101 150 mg/kg (n = 16); Group 2, morphine 5
      mg/kg (n = 16); Group 3, RB 101 vehicle (n = 15). Morphine 5 mg/kg produced
      significant depression of respiratory rate at 30 min postinjection when compared
      with RB 101 150 mg/kg and RB 101 vehicle (mean percent change in respiratory rate
      was 78.5% compared with 87.7% and 92.4%, respectively, where 100% = no change).
      These results suggest that drugs such as RB 101 may produce antinociception with
      minimal effects on respiration.

PMID- 9024029
TI  - Nitroglycerin does not alter pulmonary vascular permeability in isolated rabbit
      lungs.
AB  - Nitroglycerin (NTG) produces vasodilation by releasing nitric oxide (NO) at the
      cellular level. Other studies have suggested that NO may directly alter vascular
      permeability and may alter the development of tissue injury. We therefore
      examined the effects of NTG on vascular permeability in the buffer-perfused
      rabbit lung under normal conditions and during lung injury. Vascular permeability
      was assessed by measurement of the capillary filtration coefficient (Kf,c). In
      normal lungs, NTG did not alter Kf,c or the rate of weight gain. Oxidant lung
      injury was produced by the addition of purine and xanthine oxidase and resulted
      in increased Kf,c and increased weight gain. However, NTG did not alter these
      effects of oxidant lung injury. We conclude that NTG does not alter pulmonary
      vascular permeability in either normal or oxidant-injured lungs.

PMID- 9024030
TI  - The role of nitric oxide in the cerebrovascular response to hypercapnia.
AB  - Laser Doppler flowmetry was used to further investigate the role of nitric oxide
      (NO) in CO2-induced cerebrocortical hyperemia in rats. A second objective was to
      elucidate the source(s) of the NO involved in the response to hypercapnia. We
      used the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) to
      inhibit NO synthase (NOS) and 7-nitroindazole (7-NI) to selectively inhibit brain
      or nonendothelial NOS. Rats were anesthetized with a single dose of
      intraperitoneal (IP) pentobarbital (65 mg/kg) for surgery; 60-90 min later they
      were ventilated with 1.0% halothane in 30% O2 for 1 h to achieve a steady state.
      The animals were assigned to one of five groups. A control group (n = 9) was
      infused with 1 mL of saline. The second group (n = 10) received 20 mg/kg of L
      NAME intravenously (IV). A third group (n = 9) also received L-NAME; in addition,
      cerebrocortical laser Doppler flow (LDF) and mean arterial pressure (MAP) were
      restored to baseline using the NO donor sodium nitroprusside (SNP). In a fourth
      group (n = 9), MAP was increased to the level usually seen after L-NAME with an
      infusion of phenylephrine (0.5-5 micrograms.kg-1.min-1). A fifth group (n = 11)
      received 7-NI at 40 mg/kg IP. The hypercapnic response of LDF was tested in all
      groups by adding 5% CO2 to the inspired gas at 30-45 min posttreatment; all
      changes in LDF were significant. In the control group, hypercapnia induced a 70%
      +/- 24% increase in LDF. In the L-NAME-treated group, the response was decreased
      to 36% +/- 22% at a posttreatment LDF that was 25% +/- 13% lower than the pre-L
      NAME level. In the group where baseline LDF and MAP were restored with SNP, the
      CO2 response was 56% +/- 15% (not significant versus control). In the group in
      which MAP was increased with phenylephrine, the response to hypercapnia was 48%
      +/- 22% at a posttreatment LDF unchanged from pretreatment. These data suggest
      that increased vascular tone or the absence of basal NO after NOS inhibition
      influenced the vasodilator response to hypercapnia. In the 7-NI-treated group the
      response to hypercapnia was 38% +/- 3%, significantly attenuated at a
      posttreatment flow only 14% +/- 7% lower than pre-7-NI. We conclude that 1)
      endothelial NO does not mediate the response to hypercapnia but may have a
      permissive role in the response and 2) that brain NO may have an important role
      in response to hypercapnia.

PMID- 9024031
TI  - Effects of nitric oxide on blood-brain barrier disruption caused by intracarotid
      injection of hyperosmolar mannitol in rats.
AB  - We performed this study to evaluate the effects of changing the level of nitric
      oxide (NO) on disruption of the blood-brain barrier (BBB) by hyperosmolar
      mannitol. Under isoflurane anesthesia, control rats (control group, n = 6) were
      given infusions with 25% mannitol into the internal carotid artery before
      measuring the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C
      AIB). In the CAS group (n = 6), [3-(cis-2,6-dimethyl piperidino)-sydnonimine]
      (CAS 754), a NO donor, was injected to decrease the mean arterial pressure (MAP)
      to 55 mm Hg and in the L-NAME group (n = 6), NG-nitro-L-arginine methyl ester (L
      NAME), a NO synthase inhibitor, was injected before administering mannitol. In
      additional control animals (control + P group, n = 6) and additional CAS 754
      treated animals (CAS + P group, n = 6), phenylephrine was infused to keep MAP at
      130 mm Hg during the experimental period. In the control group, with mannitol
      injection, the Ki of the ipsilateral cortex (IC) where mannitol was injected
      increased to 4.3 times that of the contralateral cortex (CC) (17.2 +/- 2.9 vs 4.0
      +/- 2.6 microliters.g-1.min.1). Without blood pressure control, the Ki of the IC
      of the CAS group (7.0 +/- 4.5) was lower and that of the L-NAME group (26.2 +/-
      12.7) was higher than that of the control animals. At the same MAP, the Ki of the
      IC of the CAS + P group (9.6 +/- 3.1) was significantly lower than that of the
      control + P group (21.3 +/- 14.5) or that of the L-NAME group. There was no
      significant difference in the Ki of the IC between the control + P and the L-NAME
      groups. In conclusion, L-NAME worsened BBB disruption induced by hyperosmolar
      solution, which may be due to the pressure effect of L-NAME. CAS 754 was
      effective in attenuating disruption of the BBB caused by hyperosmolar mannitol.
      This effect is apparently not due to decreased MAP.

PMID- 9024032
TI  - Epidural dexamethasone reduces the incidence of backache after lumbar epidural
      anesthesia.
AB  - We performed a prospective, randomized, double-blind study to compare the effect
      of epidural dexamethasone on the incidence of postepidural backache after
      nonobstetric surgery. One thousand unpremedicated ASA physical status I or II
      patients scheduled for hemorrhoidectomy were randomly assigned to two groups:
      Group I patients received 25 mL 2% lidocaine with epinephrine 1:200,000 and 1 mL
      dexamethasone (5 mg) epidurally. Patients were interviewed at 24,48, and 72 h
      postoperatively using a standard visual analog scale (VAS) for evaluation of
      postepidural backache. A patient was considered to have postepidural backache
      when the postoperative VAS score was higher than the preoperative score. The
      incidence of postepidural backache in Group I patients for the 3 days were 22.8%,
      17.4%, and 9.2%, all of which were significantly more frequent than observed in
      Group II patients (7.4%,5.6%, and 2.8%, P < 0.01). The severity and duration of
      postepidural backache were also significantly decreased in Group II patients. In
      our study, there was a significant association between postepidural backache and
      multiple attempts at epidural needle insertion. In summary, epidural
      dexamethasone reduced the incidence and severity of postepidural backache.

PMID- 9024033
TI  - Computed tomographic study of parascalene block.
AB  - Parascalene block is a technique of blocking the brachial plexus at the lateral
      border of the anterior scalene muscle superior to the clavicle. The objective of
      this study was to define the position of the needle in parascalene block with
      relationship to the brachial plexus and the dome of the pleura, which is
      important in determining whether this technique minimizes the incidence of
      pneumothorax. In the first group, 10 patients scheduled for minor upper extremity
      surgery agreed to parascalene block, which was performed in the computed
      tomographic examination room. In the second group, 10 volunteers agreed to have
      markers placed at the point where a needle would be inserted for parascalene
      block. The computed tomographic study at the level of the needle insertion or the
      marker revealed that this level was superior to the dome of the pleura. The
      distances from the skin to the interscalene groove and the interscalene groove to
      the first rib at the level of the needle insertion or the marker in both groups
      were measured to be 17 +/- 4 mm and 15 +/- 3 mm, respectively. This study
      suggests that the level of the parascalene needle entry is superior to the dome
      of the pleura. At this level, the incidence of pneumothorax should be minimized.

PMID- 9024034
TI  - Continuous popliteal sciatic nerve block: an original technique to provide
      postoperative analgesia after foot surgery.
AB  - Our study describes an original technique of continuous popliteal sciatic nerve
      block (CPSB) (Group A, 60 patients) and compares its analgesic efficacy after
      foot surgery with intramuscular (IM) opioids (Group B, 15 patients) and
      intravenous patient-controlled analgesia (IV PCA) with morphine (Group C, 45
      patients). CPSB was performed using Singelyn's landmarks. The sciatic nerve was
      localized with a short-beveled needle connected to a peripheral nerve stimulator.
      A 20-gauge catheter was placed at the same depth as the needle with a Seldinger
      technique. Thirty milliliters of 1% mepivacaine with epinephrine 1/200,000 was
      injected and followed by a continuous infusion of 0.125% bupivacaine with
      sufentanil 0.1 microgram/mL and clonidine 1 microgram/mL at 7 mL/h for 48 h.
      Postoperative analgesia (intravenous [IV] propacetamol [PRO] and/or IM
      piritramide [DIPI]) was standardized. Postoperative pain score (PPS),
      supplemental analgesia, and side effects were noted. CPSB was easy to perform in
      55 patients (92%). In Group A, highest and mean PPS were significantly lower, and
      the mean dose of PRO was reduced by 62% and 36% when compared with Group B and C,
      respectively. Only 8% of patients required postoperative opioid in Group A
      compared with 91% and 100% in Groups B and C, respectively. No immediate or
      delayed complications other than postoperative technical problems (kinked or
      broken catheter 25%) were noted in Group A. In conclusion, CPSB is easy to
      perform, safe, and a more efficient technique than parenteral opioid for
      providing postoperative analgesia after foot surgery.

PMID- 9024035
TI  - A common epineural sheath for the nerves in the popliteal fossa and its possible
      implications for sciatic nerve block.
AB  - Sciatic nerve block in the popliteal fossa is associated with a highly variable
      success rate. Frequently, anesthesia is profound in the distribution of both the
      tibial (TN) and common peroneal nerves (CPN), although the response to nerve
      stimulation or paresthesia is obtained in the distribution of one division of the
      nerve. However, anesthesia in the distribution of only one division of the nerve
      is also a common occurrence under apparently identical clinical circumstances.
      Looking for a possible role of a common epineural sheath in these phenomena, we
      injected dye into the epineural sheath of the tibial nerve in 10 cadaver legs and
      observed its spread within the sheath. Injections of 15 mL and 30 mL of the dye
      resulted in a proximal spread of 147 +/- 34 mm and 172 +/- 50 mm, respectively,
      from the injection point 10 cm below the popliteal fossa crease. In a majority of
      the legs, the dye reached the division of the sciatic nerve in the popliteal
      fossa, bathing both the TN and CPN. Gross inspection and histologic examination
      of the sciatic nerve specimens revealed a common epineural sheath enveloping the
      TN and CPN. The presence of the common epineural sheath and its characteristics
      may have important clinical implications for sciatic nerve blockade in the
      popliteal fossa.

PMID- 9024036
TI  - Epidural anesthesia enhances sympathetic nerve activity in the unanesthetized
      segments in cats.
AB  - To evaluate compensatory sympathetic excitation during epidural anesthesia, we
      measured cardiac and renal sympathetic nerve activity during thoracic or lumbar
      epidural anesthesia in cats. Thirteen cats were divided into three groups: five
      cats received thoracic epidural anesthesia, five received lumbar epidural
      anesthesia, and three received lumbar epidural anesthesia after the carotid sinus
      and vagoaortic nerves were severed (denervated lumbar group). Heart rate (HR),
      mean arterial pressure (MAP), and cardiac and renal sympathetic nerve activity
      were measured repeatedly after administration of a single dose of 0.1 mL/kg of 1%
      lidocaine via the epidural catheter. Epidural solution spread from a median of C
      8 to T-6 in the thoracic epidural group, T-8 to L-3 in the lumbar epidural group,
      and T-7 to L-3 in the denervated lumbar group. During thoracic epidural
      anesthesia, HR, MAP, and cardiac sympathetic nerve activity decreased, while
      renal nerve activity increased. Similarly, HR, MAP, and renal sympathetic nerve
      activity decreased during lumbar epidural anesthesia, and cardiac activity
      increased. In the denervated lumbar group, HR, MAP, and renal sympathetic nerve
      activity decreased but cardiac activity remained unchanged. Sympathetic nerve
      activity in corresponding unanesthetized segments increased during thoracic or
      lumbar epidural anesthesia in association with significant decreases in MAP and
      HR. After severance of the carotid sinus and vagoaortic nerves, the absence of
      sympathetic excitation in the unanesthetized segments during lumbar epidural
      anesthesia suggests that the compensatory response is produced by the
      baroreceptor reflex response to anesthesia-induced hypotension.

PMID- 9024037
TI  - The effects of bupivacaine and ropivacaine on baroreflex sensitivity with or
      without respiratory acidosis and alkalosis in rats.
AB  - Systemic toxicity of local anesthetics causes cardiac and central nervous system
      (CNS) depression that could be enhanced in the presence of respiratory acidosis.
      We examined a potential suppression of baroreflex function with bupivacaine and
      ropivacaine during hypercapnic acidosis or hypocapnic alkalosis. Baroreflex
      sensitivity (BRS) was randomly tested in rats with one of 13 conditions during
      intravenous administration of saline (control), bupivacaine 1, 2, or 3 mg/kg, or
      ropivacaine 2, 4, or 6 mg/kg. The effects of bupivacaine (3 mg/kg) or ropivacaine
      (6 mg/kg) on BRS were also examined during hypercapnic acidosis or hypocapnic
      alkalosis. The BRS was assessed using a value of delta heart rate/ delta mean
      arterial pressure after infusion of phenylephrine (3 micrograms/kg). Both
      bupivacaine and ropivacaine (at the largest dose) significantly suppressed BRS.
      Acute respiratory acidosis (pHa 7.24 +/- 0.04, Paco2 63 +/- 4 mm Hg) enhanced
      BRS. The BRS enhanced during acidosis was also suppressed with bupivacaine and
      ropivacaine, but less so than in the absence of acidosis. The presence of
      hypocapnic alkalosis (pHa 7.55 +/- 0.03, Paco2 25 +/- 2 mm Hg) did not affect BRS
      and reversed BRS suppression caused by both drugs. Thus, bupivacaine and
      ropivacaine affect neuronal control mechanisms for maintaining cardiovascular
      stability, and acute changes of respiration could significantly modify such
      suppression.

PMID- 9024038
TI  - The inhibitory effects of local anesthetics on superoxide generation of
      neutrophils correlate with their partition coefficients.
AB  - Lidocaine and tetracaine suppress superoxide anion (O2-) generation of
      neutrophils. We examined the effects of eight local anesthetics on O2- generation
      in human neutrophils and searched for a potential relationship between the
      biological activities and the physicochemical properties of presently available
      eight local anesthetics. Human neutrophils incubated with local anesthetic and a
      Cypridina luciferin analog as a O2(-)-specific chemiluminescence probe were
      stimulated by phorbol ester. The chemiluminescence development based on O2-
      generation was monitored by a luminometer. All of the tested local anesthetics
      suppressed O2- generation in a concentration-dependent manner. The concentration
      of each of eight local anesthetics that produced 50% inhibition of peak
      chemiluminescence (IC50) had a rank order of dibucaine < tetracaine < bupivacaine
      < ropivacaine < procaine < mepivacaine < lidocaine = prilocaine. A linear
      relationship was obtained between IC50 values and the values of logarithm of
      partition coefficient (log P) of eight local anesthetics; log (IC50 in molarity)
      = -1.252 - 0.514 x log P, r2 = 0.891, P < 0.001. Unlike with staurosporine, which
      inhibits protein kinase C (PKC), no effect was observed on the O2- generation in
      the presence of tetrodotoxin (TTX), veratridine (VTD), or amiloride. These
      results suggest that the inhibitory effects of local anesthetics on O2-
      generation of neutrophils are predicted by physicochemical properties of the
      drugs, especially partition coefficients.

PMID- 9024039
TI  - Uptake of desflurane and isoflurane during closed-circuit anesthesia with
      spontaneous and controlled mechanical ventilation.
AB  - Although theoretical models predict uptake of inhaled anesthetics during closed
      circuit anesthesia (CCA), clinical data for most anesthetics are conflicting or
      non-existent. In addition, the effects of patient characteristics and mode of
      ventilation on anesthetic uptake are unclear. Forty-one ASA physical status I or
      II adult patients undergoing a variety of 1-1.5 h surgical procedures were
      randomly allocated to receive CCA with desflurane or isoflurane with ventilation
      being either spontaneous or controlled. An end-expired anesthetic concentration
      of 1.3 minimum alveolar anesthetic concentration (MAC) was maintained by
      continuous injection of the liquid anesthetic into the circuit using a syringe
      pump. After an initial 4-min wash-in period, uptake during the first hour of CCA
      was nearly constant. Uptake was the same whether ventilation was spontaneous or
      controlled. Patient characteristics (age, height, weight, weight3/4, and body
      surface area) were comparable between groups and did not correlate with uptake.
      The virtually constant uptake after wash-in of desflurane and isoflurane
      contrasts with the square root of time model of Lowe and Ernst. These findings
      may greatly simplify CCA.

PMID- 9024040
TI  - The efficacy of the "BURP" maneuver during a difficult laryngoscopy.
AB  - The displacement of the larynx in the three specific directions (a) posteriorly
      against the cervical vertebrae, (b) superiorly as possible, and (c) slightly
      laterally to the right have been reported and named the "BURP" maneuver. We
      evaluated the efficacy of the BURP maneuver in improving visualization of the
      larynx. Six hundred thirty patients without obvious malformation of the head and
      neck participated in this study. We divided the degree of visualization of the
      larynx using laryngoscopy into five grades and compared the visualization of the
      larynx using the BURP maneuver with that of laryngoscopy with and without simple
      laryngeal pressure ("Back"). The maneuver of Back and BURP significantly improved
      the laryngoscopic visualization from initial inspection. The BURP maneuver also
      significantly improved the visualization compared with the Back maneuver. We
      concluded that the BURP maneuver improved the visualization of the larynx more
      easily than simple back pressure on the larynx.

PMID- 9024041
TI  - Fatal air embolism due to perioperative blood recovery.
AB  - This study was initiated to investigate the incidence of acute mortality from air
      embolism associated with perioperative blood recovery and the causative factors
      and common characteristics of such fatalities. All facilities providing
      transfusion services in New York State are required to report severe adverse
      reactions to, and the total number of, transfusion and blood recovery procedures
      performed. Relevant data for the period from January 1990 to June 1995 were
      tabulated. During this time, 127,586 perioperative blood recovery procedures were
      performed, and 8,955,619 conventional blood components were transfused. The
      frequency of fatal air embolism after readministration of recovered blood was
      approximately 1:30,000-1:38,000; none followed conventional transfusion.
      Characteristics common to the fatalities (including an additional case reported
      before the study interval) were examined; all involved reinfusion of recovered
      blood under pressure. In the population studied, the incidence of fatal air
      embolism after the perioperative readministration of recovered blood was
      significantly higher than that after conventional transfusion. A model of such a
      system demonstrated that as much as 200 mL of air could enter the circulation in
      as little as 4 s, rendering visual detection and intervention extremely
      difficult. Education and guidelines to reduce the risk and mortality associated
      with this procedure are recommended.

PMID- 9024042
TI  - Premedication in the United States: a status report.
AB  - We undertook a mailing survey study to assess the current practice of sedative
      premedication in anesthesia. A total of 5396 questionnaires were mailed to
      randomly selected physician members of the American Society of Anesthesiologists.
      Forty-six percent (n = 2421) of those sampled returned the questionnaire after
      two mailings. The reported rate of sedative premedication in the United States
      varied widely among age groups and geographical locations. Premedicant sedative
      drugs were least often used with children younger than age 3 years and most often
      used with adults less than 65 years of age (25% vs 75%, P = 0.001). Midazolam was
      the most frequently used premedicant both in adults and children (> 75%). When
      analyzed based on geographical locations, use of sedative premedicants among
      adults was least frequent in the Northeast region and most frequent in the
      Southeast region (50% vs 90%, P = 0.001). When the frequency of premedication was
      examined against health maintenance organization (HMO) penetration (i.e., HMO
      enrollment by total population) in the various geographical regions, correlation
      coefficients (r) ranged from -0.96 to -0.54. Multivariable analysis revealed that
      HMO penetration is an independent predictor for the use of premedication in
      adults and children. The marked variation among geographical areas in premedicant
      usage patterns underscores the lack of consensus among anesthesiologists about
      the need for premedication. The data suggest that HMO participation may affect
      delivery of this component of anesthetic care.

PMID- 9024043
TI  - The relaxing effect of ketamine on isolated rabbit lower esophageal sphincter.
AB  - We used ketamine to investigate the effects and intracellular mechanisms of
      several anesthetics on strips of lower esophageal sphincter (LES) from rabbits.
      Ketamine induced dose-dependent relaxation of LES preparations. It increased the
      content of 3',5'-cyclic adenosine monophosphate (cAMP) dose-dependently, but
      decreased that of 3',5'-cyclic guanosine monophosphate (cGMP). Pretreatment with
      nicotinic acid, an inhibitor of adenylate cyclase, along with atropine to block
      neurogenic effects, antagonized ketamine-induced relaxation. Pretreatment with N
      [2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89),
      a selective antagonist for cAMP-dependent protein kinase, similarly antagonized
      the relaxant effect of ketamine. Cholera toxin and dibutyryl cAMP induced LES
      relaxation. However, dibutyryl cGMP induced little LES relaxation, and
      pretreatment with NG-nitro-L-arginine or methylene blue did not alter the
      relaxant effect. Atropine, propranolol, phentolamine, vasoactive intestinal
      peptide (VIP) antagonist, and tetrodotoxin did not affect the ketamine-induced
      relaxation. This response, however, was potentiated in the presence of
      indomethacin or diphenhydramine. Ketamine-induced relaxation was inhibited in the
      presence of verapamil. These findings suggest that ketamine induces relaxation of
      LES, in part, by modulating the activity of adenylate cyclase and in part by
      inhibiting transmembrane influx of Ca2+.

PMID- 9024044
TI  - Transurethral resection of the prostate (TURP) syndrome: a review of the
      pathophysiology and management.

PMID- 9024045
TI  - Paraplegia after intraoperative celiac plexus block.

PMID- 9024046
TI  - Spinal anesthesia for cesarean section in a case of pemphigus foliaceous.

PMID- 9024047
TI  - Coagulopathy induced by hydroxyethyl starch.

PMID- 9024048
TI  - Increased pressures in the retrograde blood cardioplegia line: an unusual
      presentation of cold agglutinins during cardiopulmonary bypass.

PMID- 9024049
TI  - Markedly prolonged paralysis after mivacurium in a patient apparently
      heterozygous for the atypical and usual pseudocholinesterase alleles by
      conventional biochemical testing.

PMID- 9024050
TI  - Spinal anesthesia for a patient with a calcium channel mutation causing
      hypokalemic periodic paralysis.

PMID- 9024051
TI  - Use the correct statistical test.

PMID- 9024052
TI  - Postarthroscopic meniscus repair analgesia with intraarticular ketorolac or
      morphine.

PMID- 9024053
TI  - Dispensing with the KCl dispensing problem.

PMID- 9024054
TI  - Overreaction to latex allergy?

PMID- 9024055
TI  - Direct faxing of laboratory results into the operating room.

PMID- 9024057
TI  - Tolerance of the laryngeal mask airway.

PMID- 9024056
TI  - Food and Drug Administration guidelines for machine checkout need modification.

PMID- 9024058
TI  - Removal of laryngeal mask airway guide after endotracheal intubation.

PMID- 9024059
TI  - Types of colloid therapy in critically ill patients.

PMID- 9024060
TI  - Unusual complication of a nasogastric tube insertion.

PMID- 9024061
TI  - HIERanarchy: the state of the art in immunohistochemistry.

PMID- 9024062
TI  - Positive Lyme disease serology in patients with clinical and laboratory evidence
      of human granulocytic ehrlichiosis.
AB  - In 10 consecutive patients with an acute febrile illness, human granulocytic
      ehrlichiosis was confirmed with specific polymerase chain reaction studies,
      serologic conversion, or both. Although no patients had the clinical features
      most suggestive of early Lyme disease (eg, erythema migrans or cranial nerve
      palsy), tests for antibody to Borrelia burgdorferi produced a reaction in most
      patients. In 6 of 7 patients (86%) with evaluable results, enzyme-linked
      immunosorbent assay yielded positive or equivocal findings, and an immunoblot
      technique yielded positive findings in 60% to 90% of patients, depending on the
      criteria used for interpretation. Inasmuch as approximately 25% of nymphal Ixodes
      scapularis ticks in Westchester County, New York, are infected with B
      burgdorferi, the probability that at least 9 of these patients were coinfected
      with B burgdorferi and human granulocytic ehrlichiosis by the same tick bite is
      estimated to be .00003. These observations suggest that serodiagnosis is
      insufficient to establish the presence of coinfection with B burgdorferi.

PMID- 9024063
TI  - Detection of antibodies to Coccidioides immitis by enzyme immunoassay.
AB  - Two hundred twenty-six specimens (160 serum samples, 66 cerebrospinal fluid
      samples) were tested with the Meridian Premier Coccidioides enzyme immunoassay
      (MPC-EIA), and the results were compared with those of conventional serologic
      tests detecting complement-fixing (CF) and tube precipitin (TP) antibodies. Of
      the 73 positive specimens by CF, 72 were positive by MPC-EIA (72 IgG positive, 48
      IgM positive) and 1 was indeterminate. Of the 132 specimens negative by CF, 126
      were negative by MPC-EIA, 3 were IgM positive only, and 3 were indeterminate. Of
      the three patients with specimens positive for IgM only, CF demonstrated
      seroconversion within a month in one. All 21 specimens that displayed
      anticomplementary activity by CF were confirmed negative by agar gel
      immunodiffusion for CF antibodies (IDCF) and TP antibodies (IDTP); 20 of these
      serum samples were also negative by MPC-EIA, and 1 was indeterminate. After
      exclusion of the 25 specimens with anticomplementary or indeterminate activity,
      results of MPC-EIA were in agreement with those of CF in 99% of specimens. With
      CF as reference, MPC-EIA had a specificity of 98%, sensitivity of 100%, and
      positive and negative predictive values of 96% and 100%, respectively.
      Correlation coefficient values from linear regressions of log-2 CF titer vs MPC
      EIA IgG index values were calculated at .290 for serum samples and .931 for
      cerebrospinal fluid.

PMID- 9024064
TI  - Clinically relevant, cost-effective clinical microbiology. Strategies to decrease
      unnecessary testing.

PMID- 9024065
TI  - T-cell blast crisis in chronic myelogenous leukemia. Immunophenotypic and
      molecular biologic findings.
AB  - T-cell blast crisis in chronic myelogenous leukemia is rare. We examined three
      patients (ages 35 to 72 years) in whom T-cell blast crisis developed 11 to 36
      months (mean, 25 months) after diagnosis of chronic myelogenous leukemia and who
      died 4 to 12 months (mean, 7 months) thereafter. Two patients had diffuse
      lymphadenopathy, and the third had marked lymphocytosis (white blood cell count
      217,000/microL, with 90% circulating blasts). In all three patients, neoplastic
      cells had the appearance of lymphoblasts and were immunoreactive for T-cell
      markers by immunohistochemical or flow cytometric analysis or both. Molecular
      diagnostic studies revealed the presence of a bcr-abl oncogene rearrangement in
      all three cases, but none exhibited a clonal T-cell receptor delta, beta, or
      gamma chain gene rearrangement. One case exhibited deletion of the J delta 1
      region of both delta chain genes. The significance of these findings is
      discussed, and they are compared with those of other reported cases of T-cell
      blast crisis in chronic myelogenous leukemia.

PMID- 9024066
TI  - Malignant hematopoietic breast tumors.
AB  - Hematopoietic neoplasms involving the breast, although less common than breast
      carcinoma, are often clinically indistinguishable from other breast tumors.
      Microscopically, these tumors can mimic primary carcinoma of the breast,
      especially in limited material such as needle biopsy specimens. Forty-five
      hematopoietic breast neoplasms including 21 primary non-Hodgkin's lymphomas
      (NHLs), 19 secondary NHLs, 1 undetermined NHL, 1 lesion secondary to Hodgkin's
      disease, and 3 granulocytic sarcomas were reviewed with regard to histologic
      subtype, morphologic features, and immunophenotype. The median age of patients at
      presentation was 67 years for those with primary NHLs and 61 years for those with
      secondary NHLs. The majority of lymphomas were intermediate or high grade.
      Diffuse large cell type was by far the most common histologic subtype. No
      lymphomas resembling lymphomas of mucosa-associated lymphoid tissue were
      identified in this series, suggesting that such lymphomas are rare in breast
      compared with other sites such as the gastrointestinal tract and lung. Four
      primary NHLs, 2 secondary NHLs, and 1 granulocytic sarcoma were initially
      misdiagnosed as carcinomas; three patients underwent radical mastectomy, and at
      least three other patients nearly received surgical treatment. One primary
      anaplastic large cell lymphoma of B-cell origin was identified that closely
      resembled poorly differentiated ductal carcinoma. "Single file" or targetoid
      patterns with extensive sclerosis mimicking invasive lobular carcinoma was common
      in lymphomas and was seen in one of the granulocytic sarcomas. In addition, two
      breast lymphomas, one of B-cell phenotype and the other of T-cell phenotype,
      showed frequent signet ring cells, which potentially could be confused with
      lobular carcinoma. Despite a number of recent articles on lymphomas of the
      breast, it appears that these tumors continue to be confused with carcinomas.
      Histologic features suggestive of lymphomatous involvement include absence of in
      situ carcinoma, frequent individual karyorrhectic cells, lymphoepithelial
      lesions, and cellular discohesiveness.

PMID- 9024067
TI  - Value of neutrophil CD16 expression for detection of left shift and acute-phase
      response.
AB  - Fc gamma RIII (CD16) expression of neutrophil granulocytes was measured in 156
      patients by means of fluorescence-labeled antibodies with a flow cytometer.
      Results were compared with (1) 400-cell manual differential count; (2) left shift
      flagging on hematology analyzers; (3) absolute neutrophil count; and (4) acute
      phase protein levels. Asynchrony was noted between neutrophil CD16 expression and
      microscopically defined neutrophil stage, particularly in heavily left-shifted
      samples, which made it impossible to reliably enumerate immature neutrophils on
      the basis of CD16 expression. According to receiver operating characteristics,
      the absolute count of CD16-negative neutrophils was highly discriminatory for
      detection of left shift, with an area under the curve (AUC) of 0.842 +/- 0.03
      (SE) and maximum efficiency of 81% +/- 3%, but absolute neutrophil count was not
      significantly inferior (0.821 +/- 0.03 and 76% +/- 3%). STKS and SE9000 flagging
      demonstrated efficiency of 76% +/- 3% and 81% +/- 3%, respectively. For detection
      of acute-phase response, absolute neutrophil count (AUC, 0.836 +/- 0.04; maximum
      efficiency, 80% +/- 4%) outperformed both quantitative neutrophil CD16 expression
      (0.760 +/- 0.05; 75% +/- 4%) and absolute CD16-negative neutrophil count (0.757
      +/- 0.05; 71% +/- 4%); absolute band count performed similarly (0.853 +/- 0.04;
      79% +/- 4%) and showed high efficiency at high sensitivity and specificity.
      Efficiency of analyzer flagging for detection of acute-phase response was not
      superior to absolute neutrophil count (STKS, 77% +/- 4%; SE9000, 78% +/- 4%). In
      conclusion, the diagnostic value of measuring neutrophil CD16 expression was
      generally similar to that of less complicated analytes.

PMID- 9024068
TI  - A new method for characterization and epitope determination of a lupus
      anticoagulant-associated neutralizing antiprothrombin antibody.
AB  - A patient had both lupus anticoagulant hypoprothrombinemia syndrome and celiac
      disease. The presence of a neutralizing antiprothrombin antibody in the patient's
      serum was demonstrated by coagulation tests, immunoadsorption, and Western blot
      analysis. The probable cause for the severe hypoprothrombinemia was clearance of
      prothrombin-antibody complexes from the circulation. Studies showed the
      antiprothrombin antibody binding to human prothrombin was phospholipid- and
      Ca(++)-independent; the antibody did not bind to human thrombin. The target
      epitope of the antibody was studied by Western blot analysis of mutated
      recombinant human prothrombin molecules. The antibody reacted with the fragment 2
      A region of prothrombin, spanning the second kringle domain and the thrombin A
      chain within prothrombin. Based on this new method, the proposed mechanism for
      the neutralizing action of the antibody is impairment of prothrombin activation
      by the prothrombinase complex, either by steric hindrance of the hydrolysis of
      prothrombin by factor Xa or by interference of the interaction of prothrombin
      with factor Va; both reactions are required for efficient conversion of
      prothrombin to thrombin.

PMID- 9024069
TI  - Effusion cytology after extrapleural pneumonectomy for treatment of malignant
      mesothelioma.
AB  - Extrapleural pneumonectomy to treat malignant mesothelioma may offer a
      significant survival advantage for selected patients. The role of effusion
      cytology in these patients has not been previously examined. To evaluate this,
      cytology, pathology, and medical records of 26 cases in 21 patients who underwent
      extrapleural pneumonectomy because of malignant mesothelioma were reviewed.
      Positive cytologic results were noted on average 13 months later than negative
      results. Recurrence was most common in the peritoneum, followed by the
      ipsilateral thorax and contralateral thorax. Five of 11 true-negative results
      were secondary to infection; cytologic analysis revealed neutrophils in each
      case. Four of 5 false-negative cases were from the ipsilateral thorax, and no
      mesothelial cells were found. When these 4 cases are excluded, the sensitivity of
      cytologic examination in this setting was 91%, and specificity was 100%. Effusion
      cytology in patients after extrapleural pneumonectomy is an effective means of
      diagnosing recurrent malignant mesothelioma.

PMID- 9024070
TI  - Effects of chemotherapy on pathologic and biologic characteristics of locally
      advanced breast cancer.
AB  - In 42 patients with locally advanced breast cancer treated with neoadjuvant
      chemotherapy followed by surgery and radiation therapy, the effects of
      chemotherapy on tumor architecture, morphometric nuclear and nucleolar
      characteristics, DNA ploidy, proliferation index measured by mitotic activity
      index, expression of differentiation antigens, and microvessel density were
      studied. Pretreatment biopsy specimens were available to compare with mastectomy
      specimens for 24 patients, and subclavicular biopsy specimens taken before
      chemotherapy were available for 9 patients. In the remaining patients, fine
      needle aspiration was performed before chemotherapy, and morphologic and biologic
      features of the tumors could be studied only after chemotherapy. In 23 patients,
      only microscopic tumor or no tumor was left after chemotherapy, and in these
      patients we observed a characteristic pattern of relatively cellular fibrous
      tissue with lymphocytic infiltrate, ironloaded macrophages, and, when present,
      scattered foci of tumor cells in between. We found a reduction in mitotic
      activity index and in global microvessel density over all the tumors as a group.
      There was, however, no consistent pattern of changes in nuclear and nucleolar
      morphometric characteristics, DNA ploidy, and expression of differentiation
      antigens, and no pathologic or biologic features were predictive for response to
      chemotherapy.

PMID- 9024071
TI  - Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma.
AB  - Anticytokeratin antibody 34 beta E12 is advocated as an immunohistochemical stain
      for discriminating benign and malignant lesions of the prostate. Positive
      staining with 34 beta E12 is said to identify benign lesions, whereas negative
      staining is said to help substantiate a diagnosis of carcinoma. It is further
      claimed that 34 beta E12 does not stain prostate carcinoma. The studies leading
      to these conclusions used hematoxylin-eosin-stained sections of primary prostate
      lesions as controls. Although the cytokeratin content of a few cell lines of
      metastatic prostate carcinoma has been investigated, the 34 beta E12
      immunohistochemical staining of metastatic prostate carcinoma has not been
      evaluated. If 34 beta E12 positivity is present only in benign prostate cells,
      then metastatic prostate carcinoma cells should be uniformly negative with this
      stain. In 14 cases of moderate and high-grade prostate cancer with metastases to
      lymph nodes, we found 34 beta E12 positivity in 6 (43%) of 14 metastases and in 7
      (54%) of 13 primary tumors. Our findings of 34 beta E12 staining in primary and
      metastatic moderately and poorly differentiated prostate carcinoma differ from
      those reported in the literature for well-differentiated prostate carcinoma. We
      urge caution in the use and interpretation of 34 beta E12 staining for the
      diagnosis of primary and metastatic prostate carcinoma.

PMID- 9024072
TI  - Evaluation of cultures of percutaneous core needle biopsy specimens in the
      diagnosis of pulmonary nodules.
AB  - The value of cultures of tissue obtained by image-directed core needle biopsy of
      lung nodules has not been determined. Of the 250 biopsies performed during a 5
      year period in an area endemic for coccidioidomycosis, 225 (90%) were diagnostic.
      Granulomas were identified in 75 specimens, whereas 3 specimens revealed abscess.
      Ziehl-Neelsen stain was positive for acid-fast bacilli (AFB) in 2 cases.
      Spherules of Coccidioides immitis were seen in 54 of the biopsy specimens with
      granulomas. Microbiologic cultures were positive for C immitis in 5 (9.6%) of 52
      biopsy specimens. Both of the AFB-positive cases were negative by culture.
      Organisms were demonstrated in cases with abscess; however, the cultures
      submitted in 2 cases were negative. Cultures were uniformly negative in cases
      where special stains failed to reveal organisms. Cultures of core needle biopsy
      specimens are insensitive in the detection of specific microorganisms and need
      not be routinely performed.

PMID- 9024073
TI  - Proliferating cell nuclear antigen and MIB-1. An alternative to classic
      prognostic indicators in renal cell carcinomas?
AB  - Tumor progression and clinical outcome for patients with renal cell carcinomas
      (RCCs) cannot be predicted based solely on tumor staging and grading. In a
      retrospective study we have therefore attempted to analyze the capacity of
      proliferation markers to provide additional prognostic information. One hundred
      seven cases of RCC were investigated by immunohistochemical analysis using two
      different monoclonal antibodies: PC10, which recognizes a proliferating cell
      nuclear antigen (PCNA), and MIB-1, which identifies the Ki-67 antigen in formalin
      fixed, paraffin-embedded material. PCNA frequency ranged from 0% to 71% (mean,
      17%), and MIB-1 expression, from 0% to 43% (mean, 11%). PCNA scores correlated
      significantly with MIB-1 immunoreactivity. PCNA and MIB-1 immunoreactivity showed
      a significant correlation with tumor grade. A strong correlation was also
      observed for T-component of stage and MIB-1 scores, but no correlation was found
      between PCNA and T-component of stage. In univariate analysis, PCNA
      immunoreactivity and MIB-1 scores were significant predictors of survival.
      Multivariate analysis, using a Cox proportional hazard model, showed PCNA index,
      N-component of stage, and tumor grade to be independent predictors of tumor
      progression, which is not the case for MIB-1 index.

PMID- 9024074
TI  - Determination of silicon in breast and capsular tissue from patients with breast
      implants performed by inductively coupled plasma emission spectroscopy.
      Comparison with tissue histology.
AB  - A method for analysis of silicon in tissue was developed to determine silicon
      content in breast parenchymal and periprosthetic capsular tissues of patients
      with silicone or saline implants and to compare levels in tissues from normal
      (nonaugmented) breasts. It is of interest to determine whether increased silicon
      content in tissues can be associated with morbidity in patients who have received
      silicone implants. This manuscript addresses the issues involved in analysis of
      breast tissue samples for silicon and compares silicon levels with tissue
      histologic findings and patient morbidity. One hundred sixty tissue samples were
      obtained for silicon analysis from 72 patients during augmentation, capsulectomy
      with or without replacement mammoplasty, mastectomy, or biopsy procedures and
      were frozen in acid-washed polystyrene tubes at 220 degrees C until analysis.
      Samples were thawed, sectioned to approximately 0.1 g (dry weight), and digested
      in nitric acid before analysis by inductively coupled plasma emission
      spectroscopy, monitoring emission intensity at 251.6 nm. Tissue silicon levels
      (breast parenchymal and periprosthetic capsular tissue) in patients with silicone
      gel implants were much higher (mean, 9,287 micrograms/g, n = 106) than in
      patients with saline implants (mean, 196 micrograms/g, n = 37) or nonaugmented
      breasts (mean, 64 micrograms/g, n = 17). Histologic examination was performed on
      54 tissue samples stained with hematoxylin-eosin. Tissue samples were rated as to
      degree of inflammation and calcification, and amount of giant cells, foamy
      histiocytes, and vacuoles containing a colorless refractory material.
      Vacuolization and foamy histiocyte ratings correlated significantly with tissue
      silicon concentration. No correlations were found between tissue silicon
      concentration and inflammation, calcification, or giant cell rating. Implant age
      (number of years an implant was in place before sampling) correlated with
      capsular tissue silicon concentration in patients with intact implants but not in
      those with ruptured implants. No difference in tissue silicon concentration was
      found between patients with or without signs or symptoms of morbidity. Using 0.1
      g of tissue, the method was linear to 1,000 micrograms/g, and sensitivity was 3.7
      micrograms/g. Precision between runs (mean, 5.1 micrograms/g; coefficient of
      variance, 13.7%; n = 13) was calculated from multiple analyses of a bovine liver
      standard (National Bureau of Standards, reference material 1577a). Significant
      biologic variability (21.4% to 52.5%) was seen in tissues with high silicon
      levels. Paraffin-embedded, formalin-fixed tissues are not amenable to silicon
      analysis by this method, because of leaching of silicone from the tissues during
      preparation. Thus only fresh frozen tissue samples were used.

PMID- 9024075
TI  - The development of hepatocellular carcinoma in cirrhotic and noncirrhotic livers.

PMID- 9024076
TI  - Irradiated blood components.

PMID- 9024077
TI  - Irradiated blood components.

PMID- 9024078
TI  - Irradiated blood components.

PMID- 9024079
TI  - Irradiated blood components.

PMID- 9024080
TI  - Irradiated blood components.

PMID- 9024081
TI  - Alzheimer's disease in women.
AB  - The progressive and irreversible dementia of Alzheimer's disease affects both men
      and women, but women constitute the majority of persons with the disease. Women
      may also have relatively more language impairment and a tendency for greater
      psychiatric involvement. Diagnosis is founded on the recognition of clinical
      features and exclusion of other causes of dementia. The etiology of the disease
      remains unknown. Although a variety of genetic factors is increasingly suspected,
      no diagnostic genetic test is currently recommended. Recent basic science and
      clinical data suggest the possibility that estrogen may be helpful both in
      preventing and in treating Alzheimer's disease, and these potential effects may
      encourage the use of estrogen in postmenopausal women. Standard treatment for
      Alzheimer's disease involves counseling and support, as well as consideration of
      tacrine, a cholinergic agent that may stabilize the course in some patients.
      Until the cause of the disease is elucidated, however, the development of
      curative treatment is unlikely.

PMID- 9024082
TI  - Fetal heart rate changes do not reflect cardiovascular deterioration during brief
      repeated umbilical cord occlusions in near-term fetal lambs.
AB  - OBJECTIVE: Brief repetitive total umbilical cord occlusions were used to induce
      fetal asphyxia and to evaluate the interrelationships with hypotension and fetal
      heart rate decelerations. STUDY DESIGN: In 21 chronically instrumented fetal
      lambs (gestational age 126.8 +/- 0.6 days), repetitive total umbilical cord
      occlusion was performed 1 out of 2.5 minutes (n = 7), 2 out of 5 minutes (n = 9),
      or not at all (shams, n = 5). Occlusions proceeded until fetal blood pressure was
      < 20 mm Hg or failed to recover to baseline before the next occlusion. RESULTS:
      At the nadir of asphyxia pH (mean +/- SEM) was 6.84 +/- 0.02, base excess 23.1 +/
      1.0 mmol/L, and lactate 14.2 +/- 0.4 mmol/L. Two fetuses died. The pattern of
      fetal heart rate decelerations remained relatively consistent throughout the
      experiments. In contrast, after an initial phase of sustained hypertension a
      progressive fall in trough blood pressure occurred after approximately 15 minutes
      of occlusion. The blood pressure recovery time in almost all fetuses lengthened
      abruptly near the end of the occlusion series, at a variable metabolic threshold.
      This was accompanied by a significant delay in fetal heart rate recovery in only
      five fetuses. CONCLUSIONS: Fetal compromise presented with the development of
      hypotension, without change in the pattern of fetal heart rate response. These
      data illustrate the limited diagnostic value of fetal heart rate monitoring to
      identify the development of cardiovascular compromise associated with severe
      decelerations in the previously healthy fetus.

PMID- 9024083
TI  - Magnesium sulfate therapy during asphyxia in near-term fetal lambs does not
      compromise the fetus but does not reduce cerebral injury.
AB  - OBJECTIVE: Our purpose was to investigate (1) the safety of fetal magnesium
      sulfate treatment and (2) possible beneficial effects on the brain during
      perinatal asphyxia. STUDY DESIGN: In 20 chronically instrumented fetal lambs
      (gestational age 125.8 +/- 3.5 days) four total umbilical cord occlusions for 5
      minutes were repeated at 30-minute intervals. Fetuses received either saline
      solution (n = 11) or magnesium sulfate (n = 9) as a bolus of 300 mg intravenously
      2 hours before occlusions, followed by an infusion of 100 mg/hr until 1 hour
      after occlusions. RESULTS: In the treated fetuses plasma magnesium levels rose
      from 0.85 +/- 0.20 to 2.23 +/- 0.40 mmol/ L. Occlusions induced asphyxia,
      associated with mortality; 4 of 11 fetuses in the control group versus 1 of 9 in
      the magnesium-treated group died (not significant). Fetal electroencephalographic
      activity decreased and cerebral impedance increased during occlusions. Maximum
      spike and seizure activity occurred 5 to 10 hours after asphyxia. Neuronal loss
      was primarily localized in the corpus striatum. Magnesium caused no alterations
      in blood pressure, heart rate, or cerebral and peripheral blood flow, nor did it
      influence electrophysiologic responses or neuronal loss. CONCLUSIONS:
      Administration of magnesium sulfate was safe but did not offer significant
      cerebral protection from asphyxia in the near-term fetal lamb.

PMID- 9024084
TI  - Differential growth of fetal tissues during the second half of pregnancy.
AB  - OBJECTIVE: Our purpose was to examine the pattern of growth of both fetal lean
      body mass incorporating bone, brain, and muscle and subcutaneous fat mass during
      the course of normal pregnancy. We hypothesized that there are detectable
      differences in the accretion of fat versus lean body mass. STUDY DESIGN: To
      establish our method we correlated standardized cross-sectional ultrasonographic
      images of the fetal extremities with anthropometric assessment of neonatal body
      composition in 25 subjects. Subsequently 36 nonsmoking women with normal
      prepregnancy body mass index, normal glucose screening results, and no medical or
      obstetric complications were recruited. We performed 135 ultrasonographic
      examinations between 19 and 40 weeks' gestation (mean 3.8 scans per fetus, range
      2 to 6) at 4-week intervals. Lean body mass measures included biparietal
      diameter, head circumference, and femur length. Fetal subcutaneous fat and lean
      body mass were examined both in the mid upper arm and midthigh by standardized
      cross-sectional images. All neonates were born between 37 and 42 weeks' gestation
      and had normal birth weight distribution. Stepwise regression analysis
      established best-fit equations for fetal measurements obtained
      ultrasonographically. Independent variables included gestational age, maternal
      age, weight gain in pregnancy, parity, fetal gender, and maternal prepregnancy
      weight. RESULTS: Fetal bone growth was best described by a second-order quadratic
      equation demonstrating deceleration with advancing gestational age (p < 0.0001,
      R2 0.92 to 0.96). A quadratic equation that accelerates with advancing gestation
      best described lean body mass accretion in the extremities (p < 0.0001, R2 = 0.85
      to 0.86). Fetal fat deposition in the extremities was characterized by an
      accelerating quadratic equation when plotted against gestational age with
      maternal age and prepregnancy weight contributing significantly (p < 0.0001, R2 =
      0.80 to 0.81). CONCLUSION: Consistent with our hypothesis, fetal fat and lean
      body mass demonstrate unique growth profiles. We speculate that, as a result of
      an accelerated rate of growth in late gestation, the measurement of fetal fat
      will provide a more sensitive and specific marker of abnormal fetal growth when
      compared with index values of lean body mass.

PMID- 9024085
TI  - Transfer of inulin across the first-trimester human placenta.
AB  - OBJECTIVE: Our aim was to investigate the transfer of inulin from the mother to
      the first-trimester fetus. STUDY DESIGN: A bolus of inulin (5 mg/kg) was
      administered to nine healthy volunteers with pregnancies between 6 and 12 weeks
      of gestation scheduled for elective termination of pregnancy. Coelomic and
      amniotic fluid samples were obtained from the corresponding cavities between 8
      and 25 minutes after the end of the bolus of inulin. Fetal fluid inulin
      concentrations were compared with those of matched samples of maternal blood and
      urine collected simultaneously. RESULTS: Inulin was detected in all fetal and
      maternal samples. A trend toward an increasing inulin concentration was noted in
      the exocoelomic cavity with advancing time. Coelomic and maternal serum inulin
      concentrations were similar within 20 minutes after injection. Amniotic inulin
      concentrations were always lower than coelomic concentrations irrespective of
      gestational age or advancing time after injection. CONCLUSIONS: Inulin crosses
      the first-trimester human placenta from 7 weeks of gestation in quantities that
      yield measurable concentrations in both coelomic and amniotic fluids. These
      results suggest that the study of drug transfer in the first trimester of human
      pregnancy is feasible with use of samples obtained from the exocoelomic cavity.

PMID- 9024086
TI  - Angiogenin plasma levels during pregnancy.
AB  - OBJECTIVE: Our purpose was to determine the levels in plasma of angiogenin in
      healthy pregnant women and to examine whether there are differences between
      uncomplicated pregnancies and patients with the syndrome of hemolysis, elevated
      liver enzymes, and low platelets, preeclampsia-eclampsia, and highly pathologic
      Doppler flow findings without additional complications. STUDY DESIGN: Angiogenin
      was measured with a novel enzyme-linked immunosorbent assay. A case control and
      observational study was conducted in 68 healthy women from the tenth to fortieth
      weeks of pregnancy and in 18 patients with the syndrome of hemolysis, elevated
      liver enzymes, and low platelets, 21 with preeclampsia/eclampsia and 13 with
      highly pathologic Doppler flow findings at admission for delivery. RESULTS:
      Between the tenth and fortieth weeks of uncomplicated pregnancy angiogenin plasma
      levels rose from 150 to 250 ng/ml (significant correlation). In patients with
      highly pathologic Doppler flow findings angiogenin is significantly reduced
      compared with healthy pregnant matched pairs (150 vs 219 ng/ml, p < 0.01).
      CONCLUSION: Rising plasma angiogenin levels in pregnancy may reflect persisting
      placental transformation and remodeling processes: in patients with highly
      pathologic Doppler flow findings these processes are disturbed and thus placental
      function is impaired.

PMID- 9024087
TI  - Effect of three hours of hypoxia on atrial natriuretic factor gene expression in
      the ovine fetal heart.
AB  - OBJECTIVES: The current study investigated the effects of 3 hours of hypoxia on
      atrial natriuretic factor gene expression and peptide content in each of the four
      cardiac chambers of the near-term ovine fetus. STUDY DESIGN: Twenty-three
      chronically catheterized ovine fetuses at 125 to 129 days' gestation (term 145
      days) were used for this study. Fetal hypoxia was induced for 3 hours in 12
      fetuses by infusion of nitrogen into the maternal trachea. The remaining fetuses
      were used as controls. Fetal arterial PO2 and plasma atrial natriuretic factor
      concentrations were measured during hypoxia. At the end of the hypoxic period
      atrial natriuretic factor peptide contents and messenger ribonucleic acid levels
      in each cardiac chamber were determined by radioimmunoassay and Northern blot
      analysis, respectively. RESULTS: With infusion of nitrogen into the maternal
      trachea, fetal arterial PO2 was reduced within 30 minutes by an average of 8.0 +/
      0.3 (SEM) mm Hg (p < 0.0001) and remained reduced at this level throughout the
      entire hypoxic period. Plasma atrial natriuretic factor concentrations increased
      by 1152 +/- 212 pg/ml (p < 0.003) and the increase was sustained for the duration
      of hypoxia. Atrial natriuretic factor peptide and messenger ribonucleic acid
      levels were much higher in the atria than in the ventricles. Hypoxia did not
      result in alterations of atrial natriuretic factor peptide content or messenger
      ribonucleic acid abundance in each cardiac chamber. CONCLUSIONS: In the near-term
      ovine fetus, 3 hours of hypoxia resulted in greatly elevated plasma atrial
      natriuretic factor concentrations; this response was sustained for the duration
      of hypoxia. However, the increase was not associated with a detectable change in
      atrial natriuretic factor peptide content or an induction of atrial natriuretic
      factor gene expression in the atria and ventricles.

PMID- 9024088
TI  - Tissue distribution of transplanted fetal liver cells in the human fetal
      recipient.
AB  - OBJECTIVE: Our purpose was to study the tissue distribution and concentrations of
      transplanted fetal liver cells in the human fetus. STUDY DESIGN: Radiolabeled
      indium 111 fetal liver cells were injected in vivo under ultrasonographic
      guidance into 10 normal fetuses (13 to 17 weeks of gestation) before a
      prostaglandin abortion. Six fetuses were injected intraperitoneally and four
      intracardially. Another two fetuses serving as controls were injected with indium
      labeled maternal plasma. The fetuses were all alive, at least until 6 hours
      before expulsion. After expulsion the fetuses were dissected, and radioactivity
      was measured in various fetal tissues. Results for each tissue were expressed as
      percentages of the total injected dose. RESULTS: Significantly greater uptake of
      fetal liver cells in the liver, spleen, thymus, kidney, lung, and placenta was
      obtained with intracardiac than with intraperitoneal injection. Skeletal uptake
      did not differ in relation to mode of administration. With intracardiac injection
      uptake was greater in such parenchymal organs as the liver, spleen, and thymus
      (4.9%, 4.0%, and 3.9%, respectively). Uptake in the rib, clavicle, humerus, and
      sternum was 2.7%, 1.8%, 2.1%, and 1.1%, respectively. Placental uptake was 0.1%.
      The intracardiac route yielded a higher concentration of cells in different fetal
      organs than did injection of only radiolabeled maternal plasma, suggesting an
      active uptake of cells in different fetal hematopoietic organs. CONCLUSION: The
      mode of administration of fetal liver cells seems to be a major determinant of
      donor cell concentration in the transplanted human fetus and may be a significant
      determinant of the rate of successful engraftment.

PMID- 9024089
TI  - Serum beta 2-microglobulin in fetuses with urinary tract anomalies.
AB  - OBJECTIVE: Our purpose was to establish a reference range of fetal serum beta 2
      microglobulin, an index of glomerular filtration rate, and to compare the values
      obtained in fetuses with urinary tract anomalies with this range. STUDY DESIGN:
      Serum beta 2-microglobulin was measured in 53 control fetuses at 18 to 39 weeks'
      gestation and in 14 fetuses with urinary tract anomalies, 9 of which had
      simultaneous urine sampling. RESULTS: In controls fetal serum beta 2
      microglobulin had a mean value of 3.4 mg/L (95% data intervals 2.0 to 4.9) and
      did not correlate with gestational age. In the 14 fetuses with urinary tract
      anomalies beta 2-microglobulin levels were increased overall compared with
      controls (median Z score 1.7, range -0.1 to 9.2), and this was also the case in
      the five fetuses with unilateral renal disorders (median Z score 1.7, range -0.1
      to 3.8) and in a fetus who underwent vesicoamniotic shunting and had normal renal
      function at birth. Serum beta 2-microglobulin was normal in 4 fetuses with
      bilateral urinary tract obstruction and normal function at postnatal follow-up
      and also in 1 of 5 fetuses with renal failure. In fetuses with bilateral uropathy
      urinary sodium correlated with serum beta 2-microglobulin levels. CONCLUSIONS:
      Increased values of serum beta 2-microglobulin in fetuses with urinary tract
      anomalies indicate an impaired glomerular filtration rate. The finding of raised
      concentrations in fetuses with unilateral damage suggests that the compensatory
      role of the normal kidney is not complete during intrauterine life. Larger series
      are required to ascertain whether fetal blood sampling is warranted in the
      antenatal investigation of renal function, especially in view of the close
      correlation between urinary sodium and serum beta 2-microglobulin levels in
      fetuses with bilateral obstruction.

PMID- 9024090
TI  - Fibronectinase activity in cultured human trophoblasts is mediated by urokinase
      type plasminogen activator.
AB  - OBJECTIVE: Human trophoblast proteolytic activity is believed to have
      implications for early implantation events and maintenance of chorionic
      structural integrity later in gestation. Abnormal release of chorion-derived
      extracellular matrix proteins such as fibronectin may identify patients at risk
      for preterm labor and delivery. The aim of this study was to characterize the
      enzyme(s) potentially responsible for trophoblast-mediated proteolysis of
      fibronectin. STUDY DESIGN: Human term cytotrophoblasts were analyzed for their
      capacity to cleave fibronectin into discrete proteolytic fragments. Selective
      protease inhibitors were used to characterize trophoblast-derived enzymes with
      fibronectinase activity. Analysis and quantitation of fibronectin fragment
      release was determined by Western immunoblots and enzyme-linked immunosorbent
      assays. RESULTS: Fibronectinase activity in trophoblast cultures was found to be
      both cell mediated and secreted, with the release of discrete fibronectin
      fragments into the media. Cell-mediated proteolytic activity could be partially
      inhibited by serum, whereas conditioned media containing fibronectinase activity
      was completely inhibited by serum, a serine protease inhibitor, and a selective
      inhibitor of urokinase-type plasminogen activator. Digestion of fibronectin with
      pure urokinase produced a similar pattern of fibronectin fragments compared with
      fibronectinase-generated fragments. Immunodepletion of urokinase from trophoblast
      media abolished fibronectinase activity. CONCLUSIONS: Trophoblast-derived
      urokinase-type plasminogen activator has significant proteolytic activity in
      vitro with the capability of cleaving fibronectin into discrete fragments. In
      early pregnancy this activity could be part of the enzymatic cascade leading to
      uterine extracellular matrix remodeling and implantation. Later in pregnancy
      trophoblast derived urokinase could promote normal or inflammation-induced
      changes in the chorionic extracellular matrix.

PMID- 9024091
TI  - Drug actions in preeclampsia: aspirin, but not magnesium chloride or
      dihydralazine, differentially inhibits cultured human trophoblast release of
      thromboxane and prostacyclin without affecting angiotensin II, endothelin-1, or
      leukotriene B4 secretion.
AB  - OBJECTIVE: We hypothesized that aspirin Mg++, and dihydralazine affect the
      release of vasoactive agents from cultured human placental trophoblast. STUDY
      DESIGN: Cytotrophoblasts isolated from placentas of preterm or term deliveries of
      14 healthy control women and 15 preeclamptic women were cultured in Dulbecco's
      modified Eagle's medium for 5 days in the presence or absence of either 0.1
      mmol/L aspirin, 3 mmol/L magnesium chloride, or 136 ng/ ml dihydralazine.
      Vasoactive substances were quantitated by radioimmunoassay with mean +/- SEM
      percentage of untreated cells (= 100%) compared by the Mann-Whitney U test and
      analysis of variance. RESULTS: Aspirin inhibited (p < 0.01) both thromboxane and
      prostacyclin on days 1 and 2 in culture but not on days 3 to 5 unless the
      Dulbecco's modified Eagle's medium was supplemented with arachidonic acid.
      Aspirin inhibition was greater (p < 0.01) for thromboxane in cells cultured 24
      hours after preeclamptic pregnancy (preterm 29.9% +/- 6.8%, term 20.1% +/- 5.9%)
      compared with normal controls (preterm 66.3% +/- 10.6%, term 68.9% +/- 11.6%).
      Aspirin reduced (p < 0.01) the ratio of thromboxane to prostacyclin in media of
      cells from preeclampsia (untreated 27.8 +/- 7.2, aspirin 13.3 +/- 4.4), but
      aspirin had no effect on this ratio in cultures from control normal pregnancies
      (untreated 6.8 +/- 2.9, aspirin 4.8 +/- 1.1). Neither magnesium chloride nor
      dihydralazine affected trophoblast prostanoid production, and no drug altered the
      media levels of angiotensin II, endothelin-1, or leukotriene B4. CONCLUSION:
      Aspirin selectively inhibits trophoblast prostanoid production. This inhibition
      depends on the availability of arachidonic acid and the presence or absence of
      preeclampsia. Magnesium and dihydralazine effects in pregnancy are not related to
      altered release of trophoblast vasoactive compounds.

PMID- 9024092
TI  - Endothelin receptor A antagonism prevents hypoxia-induced intrauterine growth
      restriction in the rat.
AB  - OBJECTIVE: Our purpose was to investigate the hypothesis that endothelin plays a
      critical role in maternal hypoxia-induced intrauterine growth restriction. STUDY
      DESIGN: Chronic indwelling venous and arterial catheters were placed on day 17 of
      a 22-day gestation in timed-pregnant Sprague-Dawley rats. Twelve rats were
      infused with saline solution and 12 with 6 mg/kg per day FR139317, an endothelin
      receptor A-specific antagonist. For gestational days 18 to 21 half the rats in
      each infusion group were housed in a normoxic environment and the other half in a
      hypoxic (14% oxygen) environment. On day 21 an arterial blood gas level was
      determined, the rats were then anesthetized, and a hysterotomy was performed. The
      weight of each pup and its corresponding placenta was recorded. Statistical
      significance was determined by analysis of variance. RESULTS: Among the rats
      receiving saline solution infusions, fetal weights were 20% less and placental
      weights were 11% less for those housed in a hypoxic environment compared with
      those housed in a normoxic environment (p < 0.003). Among the rats receiving
      FR139317 infusions, fetal and placental weights were not significantly different
      for those in a hypoxic environment compared with those in a normoxic environment.
      The fetal and placental weights for the rats receiving FR139317 infusion in
      hypoxic or normoxic environments were similar to those receiving saline solution
      in a normoxic environment. CONCLUSIONS: Endothelin plays a critical role in
      hypoxia-induced intrauterine growth restriction. Infusion of an endothelin
      antagonist prevents the intrauterine growth restriction caused by chronic
      hypoxia.

PMID- 9024093
TI  - Fetal origin of amniotic fluid polymorphonuclear leukocytes.
AB  - OBJECTIVE: Although polymorphonuclear leukocytes are the inflammatory cells most
      frequently recovered from the amniotic cavity in cases of suspected intrauterine
      infection, the source of these cells has not been definitively determined. We
      took advantage of the gender difference between the mother and her male fetus,
      and we report four cases in which amniotic fluid polymorphonuclear leukocytes
      were identified as fetal by fluorescence in situ hybridization with probes
      specific for X and Y chromosomes. Fetal membranes were intact at the time
      amniotic fluid was obtained in all cases. STUDY DESIGN: Amniotic fluid was
      obtained from women with male fetuses in premature labor with clinical or
      laboratory evidence of infection. Cytospin preparations of amniotic fluid samples
      with polymorphonuclear leukocytes were prepared and sequentially stained with
      fluorescent reagents. To determine which cells were polymorphonuclear leukocytes,
      all replicate samples were stained with the fluorescent nuclear stain 4'-6
      diamidino-2-phenyl-indole. This allowed definition of the characteristic
      multilobed polymorphonuclear leukocytes nuclear morphologic features. The sample
      was then probed with a rhodamine-labeled probe specific for the X chromosome and
      a fluorescein-labeled probe specific for the Y chromosome to assess whether the
      polymorphonuclear leukocytes were male or female. RESULTS: Ninety percent to 99%
      of polymorphonuclear leukocytes identified by normal multiple lobed nuclear
      morphologic study on 4'-6-diamidino-2-phenyl-indole staining had an X and Y
      chromosome and were therefore fetal cells. CONCLUSIONS: These data demonstrate a
      fetal response during intraamniotic infection. Further investigation of the roles
      for maternal and fetal polymorphonuclear leukocytes in chorioamnionitis may
      provide valuable information about the critical interaction of the two immune
      responses in this setting.

PMID- 9024094
TI  - Deep loop excision for prehysterectomy endocervical evaluation.
AB  - OBJECTIVE: Our purpose was to determine whether office deep loop excision should
      replace cone biopsy for frozen-section endocervical evaluation before planned
      hysterectomy. STUDY DESIGN: This cohort study comprised 31 patients who underwent
      office deep loop excision with frozen-section analysis followed by hysterectomy
      and 50 historic controls who underwent cone biopsy with frozen-section analysis
      followed by hysterectomy. Diagnostic accuracy, margin status, presence of
      residual disease, morbidity, and cost were compared. RESULTS: Loop excision
      frozen sections had sensitivity (ectocervical specimen, 96%; deepest endocervical
      specimen, 93%), specificity (100%, 86%), and positive (100%, 88%) and negative
      (75%, 92%) predictive values similar to those of frozen cone biopsy (95%, 80%,
      98%, and 67%, respectively. No differences in margin status, presence of residual
      dysplasia, or morbidity were observed. The shorter operating room time for
      vaginal hysterectomy after loop excision (p < 0.01) resulted in an approximate
      $2000 savings. CONCLUSION: Office loop excision is a cost-effective option for
      endocervical evaluation before planned hysterectomy.

PMID- 9024095
TI  - Relevance of human papillomavirus screening in management of cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: To evaluate the utility of human papillomavirus detection in
      identifying women with abnormal Papanicolaou smears who can be safely followed up
      with cytologic study only, we conducted a study to determine the sensitivity,
      specificity, and negative and positive predictive values of a Food and Drug
      Administration-approved human papillomavirus test kit for detection of cervical
      intraepithelial neoplasia in colposcopically directed biopsy specimens. STUDY
      DESIGN: We enrolled women with abnormal Papanicolaou smears referred to a
      colposcopy clinic serving indigent patients. All 1128 women had a referral
      Papanicolaou smear, a clinic Papanicolaou smear, and a sample for human
      papillomavirus deoxyribonucleic acid test; 1075 underwent colposcopically
      directed biopsies and endocervical curettage. We used the HPV Profile kit for
      human papillomavirus testing. RESULTS: Of 486 women with low-grade squamous
      intraepithelial lesions on Papanicolaou smear, 35.4% had high-risk human
      papillomavirus deoxyribonucleic acid detected, and of 592 with high-grade
      lesions, 44.4% had high-risk human papillomavirus detected. Among 527 women with
      biopsy specimens showing cervical intraepithelial neoplasia and in 267 with
      cervical intraepithelial neoplasia grades 2 or 3, 38.7% and 56.2% had high-risk
      human papillomavirus deoxyribonucleic acid detected. However, the sensitivity of
      human papillomavirus deoxyribonucleic acid detection to identify biopsy-confirmed
      cervical intraepithelial neoplasia grades 2 or 3 was 55.7%, and the positive
      predictive value of the test was only 34.9%. CONCLUSION: Human papillomavirus
      appears to be causally associated with cervical cancer but human papillomavirus
      screening does not appear to be of value to identify women with abnormal
      Papanicolaou smears who can be safely followed up with cytologic study alone.

PMID- 9024096
TI  - Vaginal intraepithelial neoplasia: risk factors for persistence, recurrence, and
      invasion and its management.
AB  - OBJECTIVE: Our purpose was to profile patients with vaginal intraepithelial
      neoplasia, evaluate the response to treatment and define risk factors for
      persistence and progression. STUDY DESIGN: We reviewed records and histopathology
      slides of 94 patients with vaginal intraepithelial neoplasia diagnosed from 1977
      to 1986. For 74 patients with follow-up, we evaluated risk factors by univariate
      and multivariate analyses. RESULTS: Sixty-four of 94 patients (68%) had prior or
      concurrent anogenital squamous neoplasia, including 21 with invasive and 43 with
      intraepithelial. Twenty-three had prior radiotherapy, 10 had anogenital
      neoplastic syndrome, and 11 were immunosuppressed. In 52 of 74 treated patients
      (70%), vaginal intraepithelial neoplasia went into remission after a single
      treatment. In 18 patients (70%) vaginal intraepithelial neoplasia went into
      remission after a single treatment. In 18 patients (24%) recurrent vaginal
      intraepithelial neoplasia went into remission after chemosurgery, upper
      vaginectomy, or other treatments; in 4 (5%) it progressed to invasion.
      Significant multivariate risk factors for persistence or progression were
      multifocal lesions and anogenital neoplastic syndrome but not vaginal
      intraepithelial neoplasia grade, associated cervical neoplasia, or
      immunosuppression. CONCLUSIONS: Although most vaginal intraepithelial neoplasia
      goes into remission after treatment, 5% of cases may progress from occult foci to
      invasion in spite of close follow-up.

PMID- 9024098
TI  - Recurrent chlamydial infections increase the risks of hospitalization for ectopic
      pregnancy and pelvic inflammatory disease.
AB  - OBJECTIVE: We examined whether the risks of hospitalization for ectopic pregnancy
      and pelvic inflammatory disease increase with increasing numbers of chlamydial
      infections. STUDY DESIGN: A retrospective cohort design was used to evaluate the
      risks of hospitalization for ectopic pregnancy or pelvic inflammatory among
      11,000 Wisconsin women who had one or more chlamydial infections between 1985 and
      1992. Logistic regression was used to evaluate the strength of association
      between recurrent infection and sequelae. RESULTS: After adjustment in
      multivariate analyses, we observed elevated risks of ectopic pregnancy among
      women who had two (odds ratio 2.1, 95% confidence interval 1.3 to 3.4) and three
      or more chlamydial infections (odds ratio 4.5, 95% confidence interval 1.8 to
      5.3). These groups were also at increased risk for pelvic inflammatory (two
      infections: odds ratio 4.0, 95% confidence interval 1.6 to 9.9; three or more
      infections: odds ratio 6.4, 95% confidence interval 2.2 to 18.4). CONCLUSIONS: A
      unique prevention opportunity occurs at the diagnosis of any chlamydial infection
      because women with subsequent recurrences are at increased risk for reproductive
      sequelae.

PMID- 9024097
TI  - Chlamydia trachomatis and febrile complications of postpartum tubal ligation.
AB  - OBJECTIVE: Our goal was to determine whether chlamydia-infected women have a
      higher rate of febrile complications after postpartum tubal ligation. STUDY
      DESIGN: Cross-sectional analysis of 1447 women tested for chlamydial infection
      within 2 weeks of delivery and who underwent postpartum tubal ligation was
      performed. Subjects were identified with the Regenstrief Institute for Health
      Care database. Infected subjects were compared with uninfected subjects for
      incidence of fever not explained by nongynecologic sources. RESULTS: Women
      infected with Chlamydia trachomatis at delivery were more likely to experience
      febrile postoperative complications after tubal ligation (p < 0.0001, relative
      risk 9.5, 95% confidence interval 4.5 to 20.1). CONCLUSION: Women undergoing
      postpartum tuba ligation may benefit from prompt diagnosis and preoperative
      treatment of chlamydial infection.

PMID- 9024099
TI  - Measuring cervical ectopy: direct visual assessment versus computerized
      planimetry.
AB  - OBJECTIVE: Cervical ectopy has been identified as a possible risk factor for
      heterosexual transmission of human immunodeficiency virus. To accurately assess
      the importance of cervical ectopy, methods for measuring ectopy with precision
      need to be developed. The objective of this study was to evaluate the reliability
      of two methods of measuring cervical ectopy: direct visual assessment and
      computerized planimetry. STUDY DESIGN: Cervical photographs of 85 women without
      cervical disease were assessed for cervical ectopy by three raters using direct
      visual assessment and a computer planimetry method. Agreement between the two
      methods, among the three raters, and among measurements by each rater over time
      was calculated with use of intraclass correlation coefficients, where 1.0
      represents perfect agreement and 0 represents no agreement except by chance.
      RESULTS: The intraclass correlation coefficient among the three raters
      (interrater agreement) was 0.58 for direct visual assessment without application
      of acetic acid to the cervix compared with 0.72 for direct visual assessment with
      acetic acid and 0.82 for computerized planimetry with acetic acid. The intraclass
      correlation coefficient among measurements by each rater over time (intrarater
      agreement) was 0.66 for direct visual assessment without acetic acid compared
      with 0.77 for direct visual assessment and 0.83 for computerized planimetry after
      application of acetic acid. When acetic acid was used, the intraclass correlation
      coefficient between the two methods was 0.69. CONCLUSIONS: Computerized
      planimetry of cervical photographs may provide the most consistent estimate of
      the percent of ectopy. However, if time and resources make the use of computer
      planimetry difficult, direct visual assessment after application of 5% acetic
      acid appears to provide comparable estimates.

PMID- 9024100
TI  - Comparison of endometrial growth produced by unopposed conjugated estrogens or by
      micronized estradiol in postmenopausal women.
AB  - OBJECTIVE: When unopposed estrogen replacement treatment is used, what is the
      pattern of endometrial growth? Does endometrial growth differ for various dosages
      and formulations? STUDY DESIGN: A total of 87 postmenopausal women, median age 57
      years (mean 56.7 +/- 5.6 years, range 45 to 69 years), were studied in a
      prospective, randomized, open clinical trial lasting 24 weeks. The treatment arms
      consisted of micronized estradiol, 0.5 or 1.0 mg (Estrace, Bristol-Myers Squibb,
      Princeton, N.J.), and conjugated estrogens, 0.625 mg (Premarin, Wyeth-Ayerst,
      Philadelphia). Endometrial thickness was evaluated by vaginal probe
      ultrasonography at outset and after 6, 12, and 24 weeks of treatment. RESULTS:
      Endometrial growth was progressive over time; more than half the total 24-week
      growth occurred in the first 6 weeks. The mean weekly rate (+/-SD) of endometrial
      growth was similar for micronized estradiol, 1.0 mg, and conjugated estrogens,
      0.625 mg (0.19 +/- 0.15 mm for micronized estradiol, 1.0 mg, and 0.19 +/- 0.14 mm
      for conjugated estrogens, 0.625 mg). These rates differed to a statistically
      significant degree (p < 0.05) from the growth rate produced by micronized
      estradiol, 0.5 mg (0.08 +/- 0.16 mm). Both unscheduled and scheduled uterine
      bleeding was less likely among women using micronized estradiol, 0.5 mg, than
      among women using micronized estradiol, 1.0 mg, or conjugated estrogens, 0.625
      mg. CONCLUSIONS: In a 24-week trial the therapeutically equivalent estrogen doses
      produced the same mean increment in endometrial thickness, but half-strength
      estradiol produced half as much endometrial growth.

PMID- 9024101
TI  - Finnish national register of laparoscopic hysterectomies: a review and
      complications of 1165 operations.
AB  - OBJECTIVE: We evaluated the advantages and disadvantages of laparoscopic
      hysterectomy over a 2-year period when this new technique was introduced to
      several hospitals in Finland. STUDY DESIGN: A nationwide register was founded and
      a prospective multicenter survey of 1165 laparoscopic hysterectomies was carried
      out from January 1993 to December 1994. The operations were performed because of
      uterine fibroids (54%), menorrhagia (27%), dysmenorrhea (8%), endometriosis (2%),
      and other reasons (9%) by 68 gynecologists at 30 hospitals. RESULTS: The mean
      operation time was 132 minutes. The patients stayed in hospital for an average of
      3.3 days, and the mean convalescence period was 17.9 days, half that after
      abdominal hysterectomy. Complications occurred in 10.2% of the procedures:
      infections in 5.6%, vascular complications in 1.2%, urinary tract complications
      in 2.7%, and bowel complications in 0.4%. CONCLUSIONS: Laparoscopic hysterectomy
      offers a short hospital stay and convalescence time to the patient, but effective
      teaching is imperative to minimize, in particular, the risk of urinary tract
      injuries.

PMID- 9024102
TI  - Proliferation of breast epithelial cells in healthy women during the menstrual
      cycle.
AB  - OBJECTIVE: Our objective was to assess proliferation in normal breast epithelial
      cells from healthy women during the follicular and luteal phases of the menstrual
      cycle. STUDY DESIGN: We analyzed the proliferation marker Ki-67/MIB-1 by
      immunocytochemical methods in breast epithelial cells procured through fine
      needle aspiration biopsy from 47 healthy volunteers. Differences were assessed by
      Wilcoxon rank sum tests, and correlations were determined by Spearman's rank
      correlation coefficient. RESULTS: The proportion of KI-67/MIB-1-positive cells
      was higher in the luteal phase (2.04%) than in the follicular phase (1.66%). The
      values in women aged < 35 years were 2.29% and 1.13%, respectively (p = 0.003).
      In ovulating women with two aspirates during the same menstrual cycle the
      percentage of proliferating cells increased from the follicular phase (1.3%) to
      the luteal phase (2.4%) (p < 0.04). Proliferation was positively correlated with
      serum progesterone levels the day of aspiration (r = 0.34, p < 0.05). CONCLUSION:
      The fine needle aspiration biopsy technique is a valuable tool for in vivo
      studies of cell proliferation in the normal breast. Data clearly suggest a
      proliferative action of progesterone.

PMID- 9024103
TI  - Alterations in steroid hormone receptors in the tamoxifen-treated endometrium.
AB  - OBJECTIVE: Our purpose was to evaluate whether tamoxifen has estrogenic
      endometrial effects as defined by histologic study or alterations in steroid
      hormone receptor expression. STUDY DESIGN: Nineteen postmenopausal tamoxifen
      treated breast cancer patients who also had endometrial sampling were identified
      from files in the Department of Obstetrics and Gynecology. To examine the
      subgroup of 15 polyps, age-matched, non-hormonally treated patients with polyps
      (n = 8) or atrophic endometria (n = 5) served as comparison groups. Proliferative
      (n = 3) and secretory (n = 5) endometria served as procedural controls.
      Immunohistochemical studies for steroid receptors (estrogen, progesterone) were
      performed. RESULTS: Glandular cell progesterone receptor was significantly
      increased and stromal cell estrogen receptor was significantly decreased in
      tamoxifen-treated versus atrophic endometria. Progesterone receptor staining was
      not significantly different in tamoxifen-treated versus control polyps, although
      staining was high in both groups. Stromal cell estrogen receptor staining was
      significantly reduced in tamoxifen-treated versus control polyps, although there
      were no histologic differences. Reduced stromal cell estrogen receptor and
      increased glandular cell progesterone receptor staining was found in all
      tamoxifen-treated endometria regardless of the diagnosis. CONCLUSION: The
      tamoxifen-associated changes in endometrial steroid receptors support an
      estrogenic effect that is independent of histologic diagnosis and duration of
      use. This may contribute to the pathogenesis of tamoxifen-associated polyps and
      carcinomas.

PMID- 9024104
TI  - Prevalence of and risk factors for fungal vaginitis caused by non-albicans
      species.
AB  - OBJECTIVE: Our purpose was to evaluate the prevalence of symptomatic yeast
      vaginitis caused by non-albicans species among patients attending a vaginitis
      clinic over an 8-year period. STUDY DESIGN: A retrospective study of 1263
      patients with symptomatic yeast vaginitis confirmed by culture techniques was
      performed. RESULTS: The prevalence of symptomatic fungal vaginitis caused by non
      albicans species increased from 9.9% (10/101) in 1988 to 17.2% (36/209) in 1995
      (chi 2 for trend = 9.33, p = 0.002). Non-albicans species were found more
      frequently in known human immunodeficiency virus-seropositive patients (23/102 vs
      143/1161, odds ratio 2.07, 95% confidence interval 1.2 to 3.46) than in
      seronegative subjects or subjects of unknown status for the virus. Recurrent
      vaginal candidiasis was an additional risk factor for vaginitis caused by non
      albicans species (odds ratio 2.47, 95% confidence interval 1.72 to 3.52). The
      increase in non-albicans isolates during the study period was confirmed in
      stratified analysis and in the subgroup of self-referred patients with no history
      of either human immunodeficiency virus infection or recurrent vaginal
      candidiasis. CONCLUSION: The prevalence of fungal vaginitis caused by non
      albicans species has increased sharply in the setting of a vaginitis clinic. The
      characteristics of risk factors suggest that fungal cultures should be done
      routinely in human immunodeficiency virus-seropositive subjects with suspected
      vaginal candidiasis and in patients with recurrent vaginal infection.

PMID- 9024105
TI  - Menstrual cycle-associated regulation of anabolic and catabolic enzymes causes
      luteal phase-characteristic expression of sulfatide in human endometrium.
AB  - OBJECTIVE: Our purpose was to investigate the metabolic background of the
      expression of sulfoglycolipids in human endometrium during the luteal phase.
      STUDY DESIGN: We investigated the expression of sulfoglycolipids by thin-layer
      chromatography immunostaining and the activities of galactosylceramide
      sulfotransferase and arylsulfatase A, which regulate the synthesis and
      degradation of sulfoglycolipid. In addition, arylsulfatase A messenger
      ribonucleic acid was studied by reverse transcriptase polymerase chain reaction.
      RESULTS: Sulfoglycolipid expression showed a marked increase in the luteal phase
      but not in the follicular phase, whereas sialoglycolipids remained relatively
      constant. The increase of sulfoglycolipids was found to be due to 4.5-fold
      increased activation of sulfotransferase and a concurrent reduction of
      arylsulfatase A activity in the luteal phase. Arylsulfatase A messenger
      ribonucleic acid was detected in both phases and showed no significant changes.
      CONCLUSIONS: These findings suggest that increased sulfoglycolipid expression in
      the luteal phase is due to the simultaneous regulation of sulfotransferase and
      arylsulfatase A, probably by sex steroid hormones.

PMID- 9024106
TI  - Human chorionic gonadotropin directly and indirectly alters uterine arteriolar
      diameters in cycling rats.
AB  - OBJECTIVE: Our purpose was to investigate whether uterine microvascular responses
      to human chorionic gonadotropin application depend on route of administration and
      estrous cycle day. STUDY DESIGN: One uterine horn was exteriorized in
      pentobarbital-anesthetized cycling and ovariectomized rats and superfused with
      Krebs solution Uterine arterioles (64 +/- 2.1 microns) were viewed by
      videomicroscopy. Diameters were measured during a 20-minute baseline period and
      for 60 minutes during human chorionic gonadotropin suffusion (20 IU/60 ml) or 60
      minutes after intraperitoneal injection of 50 IU of human chorionic gonadotropin.
      Papaverine (100 mumol/L) suffusion maximally dilated the uterine arterioles (80
      +/- 2.6 microns). RESULTS: Suffusion of human chorionic gonadotropin-dilated
      arterioles on diestrus-1 (122% +/- 2% baseline) and diestrus-2 (118% +/- 4%
      baseline) but constricted arterioles on proestrus (78% +/- 7% baseline).
      Intraperitoneal injection of human chorionic gonadotropin resulted in arteriolar
      constriction on diestrus-2 (76% +/- 5% baseline) and proestrus (82% +/- 3%
      baseline). Ovariectomy eliminated the effects of injected but not suffused human
      chorionic gonadotropin. All results are significant at p < 0.05. CONCLUSIONS:
      Results indicate estrous cycle day-dependent direct and indirect effects of human
      chorionic gonadotropin on the resistance of uterine arterioles.

PMID- 9024107
TI  - Lymphocyte shedding from genital tract of human immunodeficiency virus-infected
      women: immunophenotypic and clinical correlates.
AB  - OBJECTIVE: Our purpose was to describe the lymphocyte subpopulations in genital
      tract samples from human immunodeficiency virus-infected women and the clinical
      correlates associated with lymphocyte shedding. STUDY DESIGN: Genital tract
      samples of women infected with human immunodeficiency virus-1 were processed for
      immunophenotyping analysis with a FACScan flow cytometer. Immunologic and
      virologic characteristics of women with and without lymphocyte shedding were
      compared with t test, Wilcoxon rank test, or Fisher's exact test. RESULTS: The
      rate of genital lymphocyte shedding among human immunodeficiency virus-1-infected
      women was 39%. Genital shedding was not related to age, race, use of
      antiretroviral therapy, or positive human immunodeficiency virus-1 culture. A
      negative rank correlation (r = -0.71, p = 0.047) between CD3+ CD4+ counts in
      peripheral blood and genital tract was observed. The majority of the lymphocyte
      cells were CD3+ CD8+, and > 80% of the CD3+ CD4+ cells were memory cells.
      CONCLUSION: The immune profile of the genital tract lymphocytes is suggestive of
      a local mucosal immune response.

PMID- 9024108
TI  - Factors influencing views of patients with gynecologic cancer about end-of-life
      decisions.
AB  - OBJECTIVE: This study was undertaken to assess the life views, practices, values,
      and aspirations of women with various stages of gynecologic cancer. STUDY DESIGN:
      A self-administered questionnaire was completed by 108 women with various stages
      of cancer and 39 women with benign gynecologic disease. The questionnaire
      included items on demographics in addition to 16 multiple choice and 4 true-false
      items. The four questions related to criteria of good care, degree of involvement
      in decision making, psychosocial well-being, religious experience, and
      aspirations form the basis of this study. The data were analyzed with the Pearson
      chi 2 test (Systat, version 5.1) with significance set at p < 0.05. RESULTS: The
      women in this study placed greatest emphasis on receiving "straight talk" (96%)
      and compassion (64%) from their physicians. The newly diagnosed group put
      significantly less emphasis on compassion (33%, p = 0.037). Less than half
      expected their physicians to cure (43%, 56% for newly diagnosed) or contain (49%)
      the disease. For these women fear was the most dominant psychosocial consequence
      of having cancer, with difficulty communicating or feeling abandoned, isolated,
      or embarrassed less common. Those who specified their ears were afraid of pain
      (63% vs 39% for patients with benign disease, p = 0.019), dying (56%), losing
      control (48%), or becoming totally dependent (46%). Seventy-six percent indicated
      that religion had a serious place in their lives, with 49% becoming more
      religious since their cancer diagnosis, whereas no one became less religious.
      Ninety-three percent believed that the religious commitment helped sustain their
      hopes. CONCLUSIONS: These data suggest that (1) physicians should aim to educate
      their patients sufficiently for them to exercise control over their experience,
      to allay their fears, and to make personal decisions that further their
      aspirations, (2) patients in different stages of disease varied in their
      perceptions of themselves and their aspirations, (3) patients are dealing with
      fear as a primary problem, and (4) women with gynecologic cancer depend on their
      religious convictions and experiences as they cope with the disease.

PMID- 9024109
TI  - Vaginal flora changes associated with Mycoplasma hominis.
AB  - OBJECTIVE: The aim of this study was to investigate any association between
      vaginal carriage of Mycoplasma hominis and genital signs and symptoms, other
      microbial findings, and some risk behavior factors in women with and without
      bacterial vaginosis. STUDY DESIGN: Women who had attended two family planning
      clinics and a youth clinic for contraceptive advice were divided depending on the
      result of vaginal culture for Mycoplasma hominis and the occurrence of bacterial
      vaginosis. The study population included 123 (12.3%) women who harbored
      Mycoplasma hominis. Those 873 (87.7%) with a negative culture for Mycoplasma
      hominis served as a comparison group. In the former group, 50 (40.7%) had
      bacterial vaginosis, which was also the case in 81 (9.3%) of the women in the
      comparison group. The groups were compared with regard to genital signs and
      symptoms, results of vaginal wet smear microscopy and other office tests, vaginal
      flora changes as detected by culture, and other means and detection of sexually
      transmitted diseases. Any history of sexually transmitted diseases and other
      genital infections, reproductive history, use of oral contraceptives, and smoking
      habits were registered. RESULTS: Women who harbored Mycoplasma hominis had
      significantly more often complained of a fishy odor, had a positive amine test, a
      vaginal pH > 4.7, and clue cells than did the comparison group; all these
      statements were true before and after bacterial vaginosis had been excluded.
      Vaginal discharge was not significantly more often complained of, and a
      pathologic discharge was not more often detected in the Mycoplasma hominis
      carriers. Ureaplasma urealyticum occurred in 75% of the Mycoplasma hominis
      positive women and in 59% of the comparison group (p = 0.001). The
      leukocyte/epithelial cell ratio did not differ significantly from that of the
      Mycoplasma hominis culture-negative controls. CONCLUSION: The study suggests that
      Mycoplasma hominis is associated with a number of genital signs and symptoms even
      after exclusion of bacterial vaginosis.

PMID- 9024110
TI  - Profet, profits, and proof: do nausea and vomiting of early pregnancy protect
      women from "harmful" vegetables?
AB  - OBJECTIVE: The purpose of this research was to test a widely publicized theory
      that nausea and vomiting of pregnancy protects women from ingesting certain
      vegetables and other foods that produce congenital anomalies and other adverse
      outcomes of pregnancy. STUDY DESIGN: The theory was tested with use of data on
      dietary intake, illness, and pregnancy outcome obtained from 549 women
      participating in a prospective, population-based study. RESULTS: No relationship
      between intake of proscribed vegetables and other foods and the presence of
      nausea and vomiting in early pregnancy was identified. Intake of proscribed foods
      was unrelated to adverse outcomes of pregnancy. CONCLUSION: It is suggested that
      claims made in the popular press about food and health relationships should be
      evaluated by the media as fiction unless supported by scientific research.

PMID- 9024111
TI  - Peripartum cardiomyopathy: an ominous diagnosis.
AB  - OBJECTIVE: Our purpose was to review and characterize the initial presentation,
      etiology, and prognosis of peripartum cardiomyopathy. STUDY DESIGN: Cases of
      peripartum cardiomyopathy confirmed by echocardiography were prospectively
      collected between 1986 and 1994. RESULTS: A total of 28 patients without an
      antecedent history of heart disease were diagnosed with peripartum
      cardiomyopathy. Common associated disorders included preeclampsia or chronic
      hypertension (19), alcohol abuse (2), family history (2), and multiple tocolytic
      therapy (2). Five deaths occurred (18% mortality), 3 patients received heart
      transplants (11%), 18 continued with cardiac impairment (64%), and only 2
      patients (7%) had regress on of cardiomyopathy. The perinatal mortality rate was
      36 per 1000 births. Six patients had seven subsequent pregnancies; 4 patients
      decompensated earlier in the subsequent pregnancy, 1 patient remained well
      compensated on medical therapy in spite of poor systolic function and a dilated
      left ventricle, and 1 patient had two subsequent pregnancies without recurrence
      of cardiac compromise. CONCLUSION: The unique hemodynamic stresses of pregnancy
      unmask previously undiagnosed cardiomyopathy in otherwise medically stable
      individuals. The prognosis for these patients is guarded.

PMID- 9024112
TI  - Contractile reserve in patients with peripartum cardiomyopathy and recovered left
      ventricular function.
AB  - OBJECTIVES: Peripartum cardiomyopathy is a rare complication of pregnancy. Thirty
      percent of patients with this disorder are reported to recover baseline
      ventricular function within 6 months of delivery, but the ability of these
      ventricles to respond to hemodynamic stress is unknown. The aim of this
      investigation was to quantitatively assess the contractile reserve of patients
      with a history of peripartum cardiomyopathy and recovered left ventricular
      function. STUDY DESIGN: Baseline left ventricular contractility was assessed by
      use of the load and heart rate-independent relationship between end-systolic
      stress and rate-corrected velocity of fiber shortening. Data were acquired from
      "recovered" patients (10.5 +/- 11.6 months after delivery) and compared with data
      from matched nonpregnant controls with use of two-dimensionally targeted M-mode
      echocardiography and calibrated subclavian pulse tracings that were recorded over
      a wide range of afterloads (end-systolic stress) generated by methoxamine (1
      mg/min) infusion. Contractile reserve was assessed by a dobutamine challenge (5
      micrograms/kg/min) and quantified as the vertical deviation of the dobutamine end
      systolic stress minus the corrected velocity of fiber shortening data point from
      the baseline contractility line. RESULTS: Patients with peripartum cardiomyopathy
      and matched controls had normal baseline heart rates, blood pressures,
      ventricular dimensions, and left ventricular function. Contractile reserve,
      however, was reduced in patients with recovered peripartum cardiomyopathy (0.30
      +/- 0.12 vs 0.17 +/- 0.04 circ/sec, p < 0.03). CONCLUSIONS: Women with a history
      of peripartum cardiomyopathy who have regained normal resting left ventricular
      size and performance have decreased contractile reserve revealed by the use of a
      dobutamine challenge test. Ventricles of these women may respond suboptimally to
      hemodynamic stress in spite of evidence of recovery by routine echocardiographic
      evaluation.

PMID- 9024113
TI  - Evaluating the risk of preterm delivery: a comparison of fetal fibronectin and
      transvaginal ultrasonographic measurement of cervical length.
AB  - OBJECTIVE: Our purpose was to compare the predictive values for preterm delivery
      of fetal fibronectin and cervical length measured by transvaginal ultrasonography
      and to determine whether performing both tests improves their separate predictive
      values. STUDY DESIGN: This prospective blinded study performed both tests on 76
      patients hospitalized with signs of premature labor between 24 and 34 weeks of
      gestation. The outcome measure was delivery before 37 weeks' gestation. RESULTS:
      The rate of preterm bith was 26.3% (20/76). The predictive values of fetal
      fibronectin and of a cervical length of < or = 26 mm, considered separately, were
      approximately equal, and the negative predictive value of each was excellent
      (86.6% and 89.1%, respectively). This value improved slightly when positive fetal
      fibronectin, a cervical length < or = 26 mm, or both defined abnormality
      (negative predictive value 94.4%). The positive predictive values, although less
      helpful, were still useful (45.2% and 50.0%, respectively). Combining both
      indicators did not noticeably improve the positive predictive value (52.4%). The
      risk of preterm delivery for a patient with a positive fetal fibronectin level
      and a short cervix was high (odds ratio 13.9, 95% confidence interval 3.7 to
      52.2). CONCLUSION: Fetal fibronectin and cervical length are approximately
      equivalent in their ability to distinguish between patients at high and low risk
      for preterm delivery. For physicians equipped to perform transvaginal
      ultrasonography, however, the additional information about the fibronectin level
      provides only slight benefits.

PMID- 9024114
TI  - Failed trial of vacuum or forceps--maternal and fetal outcome.
AB  - OBJECTIVE: Our purpose was to compare the maternal and neonatal morbidity
      associated with a failed trial of instrumental delivery with that of proceeding
      directly to cesarean section during the second stage of labor. STUDY DESIGN: All
      second-stage cesarean deliveries between January 1986 and December 1992 in a
      tertiary care teaching hospital were retrospectively reviewed. Specific maternal
      and neonatal outcome parameters were studied to compare the failed instrumental
      group with the direct-to-cesarean section group. RESULTS: Of 29,457 live births
      at > 37 weeks' gestation, 401 women had a cesarean section performed in the
      second stage of labor. There were 326 cases in which cesarean section was
      performed directly during the second stage of labor and 75 women who had a failed
      attempt of instrumental delivery (forceps 33, vacuum 25, both 17) before cesarean
      delivery was done. The three instrumental groups and the direct-to-cesarean
      section group did not differ in any of the outcome variables for either mother or
      newborn. CONCLUSIONS: Failed instrumental delivery performed as a trial of
      forceps and/or vacuum in a setting where a cesarean section can follow promptly
      is not associated with increased morbidity of either mother or baby.

PMID- 9024115
TI  - A randomized trial of a program of early postpartum discharge with nurse
      visitation.
AB  - OBJECTIVE: Our purpose was to compare an early postpartum discharge program
      versus standard postpartum care. STUDY DESIGN: A randomized controlled trial in a
      637-bed university hospital included 175 healthy women recruited at 32 to 38
      weeks gestation from physicians' offices and sonograms. Experimental intervention
      consisted of discharge 6 to 36 hours post partum with nursing care available by
      telephone or at home at 34 to 38 weeks' gestation and at < or = 48 hours and at
      3, 5, and 10 days post partum. The control included a postpartum stay of 48 to 72
      hours and standard follow-up. RESULTS: At 1 month no significant differences were
      seen in perceived maternal competence (Experimental-Control = 4.3 points [95%
      confidence interval-7.7 to 16.3]), infant weight gain (1.2 gm/ day [-2.8 to
      5.2]); identification of significant neonatal hyperbilirubinemia (rate ratio 0.50
      [0.10 to 2.51]), infant utilization of health services (rate ratio 0.88 [0.45 to
      1.73]), or predominant breast-feeding (adjusted odds ratio 1.25 [0.88 to 1.75]).
      Program participants did have significantly less frequent infant bilirubin
      testing (rate ratio 0.39 [0.17 to 0.94]). The program also enhanced perceived
      maternal competence in recent immigrants (26.9 points [2.7 to 51.5]).
      CONCLUSIONS: Early postpartum discharge coupled with prenatal, postnatal, and
      home contacts leads to no apparent disadvantage and may yield benefits for some
      mothers and infants.

PMID- 9024116
TI  - Pregnancy-induced elevation in aortic vascular smooth muscle actin in the Sprague
      Dawley rat.
AB  - A component of hemodynamic responses during pregnancy may include structural
      changes in the arterial tree. Smooth muscle alpha-actin is a major structural
      contractile protein of muscle cells. We observed a marked increase. In expression
      of actin during pregnancy in the rat aorta, suggesting a structural alteration of
      conduit arteries.

PMID- 9024117
TI  - A prospective study of calciotropic hormones in pregnancy and post partum:
      reciprocal changes in serum intact parathyroid hormone and 1,25-dihydroxyvitamin
      D.
AB  - OBJECTIVE: The purpose of this study was to examine the hormones regulating
      calcium homeostasis longitudinally in pregnancy and post partum. STUDY DESIGN:
      Twenty-three women with normal pregnancies were studied in the second and third
      trimesters and post partum. At each time blood was analyzed for ionized calcium,
      vitamin D metabolites, and intact parathyroid hormone, and a 24-hour urine
      specimen was analyzed for creatinine, calcium, and sodium. RESULTS: Urinary
      calcium excretion was 250% to 300% higher during pregnancy than post partum (p <
      0.00001). 1,25-Dihydroxyvitamin D levels were equivalent in the second and third
      trimesters but were twofold higher than postpartum values (p < 0.01). Ionized
      calcium was similar at all time points. Intact parathyroid hormone in the second
      and third trimesters was 50% of postpartum levels (p < 0.001). CONCLUSION:
      Pregnancy is associated with an increase in the levels of 1,25-dihydroxyvitamin D
      and a concomitant reciprocal fall in intact parathyroid hormone levels. The
      increase in serum 1,25-dihydroxyvitamin D values appears to be a key factor in
      providing for the increase in maternal calcium requirements during pregnancy.

PMID- 9024118
TI  - Pregnancy outcome after successful external cephalic version for breech
      presentation at term.
AB  - OBJECTIVE: Our purpose was to review the outcome of pregnancies after external
      cephalic version at term, in particular the incidence and indications of
      intrapartum cesarean section after successful external cephalic version. STUDY
      DESIGN: A prospective study was performed of 241 term pregnancies that had a
      total of 243 external cephalic versions. Each case with successful external
      cephalic version was matched to two control cases with cephalic presentation to
      compare pregnancy outcome. RESULTS: External cephalic version was successful in
      169 attempts (69.5%), of which 7 (4.1%) reverted to breech presentation. There
      was one case of abruptio placentae and eight cases (3.3%) of transient fetal
      bradycardia after the procedure. Among those who had a successful external
      cephalic version, the incidence of intrapartum cesarean section was 16.9%, which
      was 2.25 times higher than that of the control group (p < 0.005). This large
      number of abdominal deliveries was due to a significantly higher incidence of
      fetal distress and dystocic labor. The incidence of augmentation of labor was
      also significantly higher in the study group (37.7% vs 27.6%, p < 0.05).
      CONCLUSION: Pregnancies after a successful external cephalic version at term are
      not the same as those with cephalic presentation. They are at higher risk of both
      dystocic labor and fetal distress and therefore require close intrapartum
      monitoring.

PMID- 9024119
TI  - Management of the Zollinger-Ellison syndrome in pregnancy.
AB  - OBJECTIVE: There is almost no information on the management of patients with
      functional pancreatic endocrine tumors such as Zollinger-Ellison syndrome during
      pregnancy. The purpose of this study was to develop an approach for the
      management of such cases during pregnancy on the basis of experience with five
      recent cases. STUDY DESIGN: Five women with Zollinger-Ellison syndrome who had
      seven pregnancies were the subject of this study. Each patient had an initial
      evaluation to confirm the diagnosis and to establish gastrinoma location and for
      the presence or absence of multiple endocrine neoplasia type I. In patients with
      Zollinger-Ellison syndrome diagnosed before conception, various medical or
      surgical treatments were established before conception and were used to control
      acid secretion throughout the pregnancy. The presence of upper gastrointestinal
      symptoms during pregnancy, maternal and fetal complications, gender, and weight
      of the infant were determined in all cases. Acid control was determined in four
      of the five patients during six pregnancies. RESULTS: The interval between the
      onset of Zollinger-Ellison syndrome and the subsequent pregnancy varied from 0.6
      to 9.9 years (mean 6.9 +/- 1.7 years). Zollinger-Ellison syndrome was
      unrecognized before pregnancy in two patients (40%); it was diagnosed between 0.2
      and 2.4 years after the pregnancy. In three patients the time of diagnosis varied
      from 2.6 to 9 years before pregnancy. All patients had symptoms from gastric
      hypersecretion and elevated fasting serum gastrin levels that varied from 20%
      above normal to 37-fold above normal with mean of 2536 pg/ml (range 124 to 6970
      pg/ml). Four of the five patients (80%) had positive secretin and calcium
      provocative tests. Two patients had multiple endocrine neoplasia type I. The five
      patients had seven pregnancies. Acid secretion was treated during pregnancy with
      antacids only (one patient), ranitidine alone (one patient), prior curative
      gastrinoma resection (one patient, two pregnancies), prior parietal cell vagotomy
      with incomplete tumor resection (one patient, two pregnancies), and prior
      parathyroidectomy and use of ranitidine in a patient with multiple endocrine
      neoplasia type I. In five pregnancies in three of the cases, no gastric
      antisecretory medications were needed during pregnancy. The mean acid secretion
      during pregnancy was 11.9 mEq/hr (range 0 to 42 mEq/hr). In the two cases with
      poor acid control and unrecognized Zollinger-Ellison syndrome mild fetal
      complications occurred. CONCLUSIONS: It is possible for patients with Zollinger
      Ellison syndrome to have pregnancies that are not complicated by gastric acid
      hypersecretion. If the Zollinger-Ellison syndrome is diagnosed before pregnancy,
      curative resection with parietal cell vagotomy may obviate the need for gastric
      antisecretory drugs. If metastases are present or the diagnosis of Zollinger
      Ellison syndrome is made after conception, ranitidine in the lowest possible dose
      should be used to control acid secretion. If acid secretion in uncontrolled, the
      dose may be increased or omeprazole may be used.

PMID- 9024120
TI  - The relaxation responses to corticotropin-releasing factor in rat aorta are
      endothelium dependent and gestationally regulated.
AB  - OBJECTIVE: Our purpose was to examine the hypothesis that the relaxant response
      to corticotropin-releasing factor is endothelium dependent and changes during
      pregnancy. STUDY DESIGN: Relaxant responses to cumulative concentrations of
      corticotropin-releasing hormone were measured in rings of thoracic aorta,
      precontracted with phenylephrine, from pregnant and nonpregnant female rats. Each
      group consisted of 5 to 10 rats. RESULTS: The relaxation induced by corticotropin
      releasing factor in aortic rings from nonpregnant rats decreased after
      deendothelization and treatment with N omega-nitro-L-arginine methyl ester (a
      nitric oxide synthase inhibitor), LY-83,583 (a guanylate cyclase inhibitor), or
      alpha-helical corticotropin-releasing factor 9-41 (a corticotropin-releasing
      factor antagonist). The percent decrease in relaxation at 1 nmol/L of
      corticotropin-releasing factor was about 88% with deendothelization, 100% with N
      omega-nitro-L-arginine methyl ester, 76% with LY-83,583, and 100% with alpha
      helical corticotropin-releasing factor 9-41. The responses to corticotropin
      releasing factor in intact rings from rats in early pregnancy were not
      significantly different from those in the nonpregnant female rats, but the
      responses were decreased during the later stages of gestation (percent decrease
      in relaxation at 1 nmol/L of corticotropin-releasing factor about 71% at day 20
      and 98% at term). The relaxation induced by corticotropin-releasing factor during
      pregnancy was also inhibited by deendothelization, N omega-nitro-L-arginine
      methyl ester, or LY-83,583. CONCLUSIONS: The relaxant response to corticotropin
      releasing factor in the rat aorta is endothelium dependent and is mediated by the
      nitric oxide-cyclic guanosine monophosphate pathway. The receptor involved in
      this effect is alpha-helical corticotropin-releasing factor 9-41 sensitive. This
      inhibitory response is unchanged during early pregnancy but reduced toward the
      end of gestation.

PMID- 9024121
TI  - Clinical uses of intravenous immunoglobulin in pregnancy.
AB  - Intravenous immunoglobulin was licensed for use in the United States in 1981.
      Currently, there are only a few Food and Drug Administration-labeled indications
      for intravenous immunoglobulin, but up to 50 "off-label" uses are reported in the
      literature. The obstetric literature contains numerous reports on intravenous
      immunoglobulin therapy during pregnancy. This article reviews the properties,
      pharmacokinetics, mechanisms of action, and side effects of intravenous
      immunoglobulin, as well as the reported uses of intravenous immunoglobulin during
      pregnancy.

PMID- 9024122
TI  - Delayed interval delivery in a twin pregnancy with monochorionic placenta.

PMID- 9024123
TI  - Long-term implications of cesarean section.

PMID- 9024124
TI  - A randomized comparison of Burch colposuspension and abdominal paravaginal defect
      repair.

PMID- 9024125
TI  - Efficacy of methotrexate.

PMID- 9024126
TI  - Endoscopic coverage of fetal open myelomeningocele in utero.

PMID- 9024127
TI  - Congenital diaphragmatic hernia: can prenatal ultrasonography predict outcome?

PMID- 9024128
TI  - Maternal serum human chorionic gonadotropin level at 15 weeks.

PMID- 9024129
TI  - Fetal impact of forceps rotation.

PMID- 9024130
TI  - Evolution of academic divisions of cardiology.

PMID- 9024131
TI  - The business of medicine.

PMID- 9024132
TI  - How leaky is that mitral valve? Simplified Doppler methods to measure regurgitant
      orifice area.

PMID- 9024133
TI  - Cytokines score a knockout. Harnessing gene targeting to gain insight into the
      pathogenesis of myocarditis.

PMID- 9024134
TI  - Nitric oxide: nature's naturally occurring leukocyte inhibitor.

PMID- 9024135
TI  - Platelet-derived growth factor and arterial response to injury.

PMID- 9024136
TI  - Oxidative stress produced by angiotensin too. Implications for hypertension and
      vascular injury.

PMID- 9024137
TI  - Insulin-dependent diabetes mellitus and nitrovasodilation. Important and complex
      interactions.

PMID- 9024138
TI  - Atrial fibrillation. A tachycardia-induced atrial cardiomyopathy.

PMID- 9024139
TI  - Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.
AB  - BACKGROUND: Familial long-QT syndrome (LQTS) is characterized by prolonged
      ventricular repolarization. Clinical symptoms include recurrent syncopal attacks,
      and sudden death may occur due to ventricular tachyarrhythmias. Three genes
      responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so
      far. We investigated mutations of these genes in LQTS families. METHODS AND
      RESULTS: Thirty-two Japanese families with LQTS were brought together for
      screening for mutations. Genomic DNA from each proband was examined by the
      polymerase chain reaction-single-strand conformation polymorphism technique
      followed by direct DNA sequencing. In four of the families, comprising 16
      patients, mutations were identified in KVLQT1; five other families (9 patients)
      segregated mutant alleles of HERG. All 25 of these patients carried the specific
      mutations present in their respective families, and none of 80 normal individuals
      carried these alleles. Mutations were confirmed by endonuclease digestion or
      hybridization of mutant allele-specific oligonucleotides. No mutation in SCN5A
      was found in any family. CONCLUSIONS: We identified nine different mutations
      among 32 families with LQTS. Eight of these were novel and account for 25% of all
      types of mutations reported to date. Such a variety of mutations makes it
      difficult to screen high-risk groups using simple methods such as endonuclease
      digestion or mutant allele-specific amplification.

PMID- 9024140
TI  - Characterization of the hyperpolarization-activated current, I(f), in ventricular
      myocytes from human failing heart.
AB  - BACKGROUND: Disease-associated electrophysiological alterations may contribute to
      the increased predisposition to arrhythmias of the hypertrophied or failing
      myocardium. An I(f)-like current is expressed in rat left ventricular myocytes
      (LVMs), its amplitude being linearly related to the severity of cardiac
      hypertrophy. Here, we report the occurrence and electrophysiological properties
      of I(f) in human LVMs. METHODS AND RESULTS: LVMs were isolated from hearts of
      three male patients undergoing cardiac transplantation for terminal heart failure
      due to ischemic dilated cardiomyopathy. The patch-clamp technique was used to
      record I(f), ie, a barium-insensitive, cesium-sensitive, time-dependent
      increasing inward current elicited on hyperpolarization. Membrane capacitance was
      244 +/- 27 pF (n = 25). I(f) occurred in all cells tested; its density measured
      at -120 mV was 2.1 +/- 0.3 pA/pF. Activation curves of I(f) (n = 24) were fitted
      by a Boltzmann function; the threshold was -55 mV; midpoint, -70.9 +/- 2.1 mV;
      slope, -5.4 +/- 0.3 mV; and maximal specific conductance, 19.6 +/- 2.5 pS/pF.
      I(f) blockade by extracellular cesium was voltage dependent. Reducing
      extracellular potassium concentration from 25 to 5.4 mmol/L caused a shift of the
      reversal potential from -12.7 +/- 0.5 to -24.8 +/- 2.1 mV and a 64% decrease of
      current conductance. CONCLUSIONS: I(f) is present in human LVMs. Its
      electrophysiological characteristics resemble those previously described in
      hypertrophied rat LVMs and suggest that I(f) could be an arrhythmogenic mechanism
      in patients with severe heart failure.

PMID- 9024141
TI  - A focal source of atrial fibrillation treated by discrete radiofrequency
      ablation.
AB  - BACKGROUND: Atrial fibrillation is usually thought to be due to multiple
      circulating reentrant wavelets. From previous studies, a focal mechanism is
      considered to be very unlikely. In this report, focal atrial fibrillation is
      defined on an ECG pattern of atrial fibrillation and later demonstrated to be due
      to a focal source. METHODS AND RESULTS: Nine patients (five men and four women,
      age, 38 +/- 7 years) with paroxysmal focal atrial fibrillation are reported here.
      All were free of structural heart disease and had frequent episodes of atrial
      fibrillation despite the use of a mean of 4 +/- 2 antiarrhythmic drugs. Atrial
      fibrillation was associated with runs of irregular atrial tachycardia or
      monomorphic extrasystoles. The electrophysiological study demonstrated that all
      the atrial arrhythmias were due to the same focus firing irregularly and
      exhibiting a consistent and centrifugal pattern of activation. Three foci were
      found to be located in the right atrium, two near the sinus node and one in the
      ostium of the coronary sinus. Six others were located in the left atrium at the
      ostium of the right pulmonary veins (n = 5) and at the ostium of the left
      superior pulmonary vein (n = 1). All atrial arrhythmias were successfully treated
      by use of a mean of 4 +/- 4 radiofrequency pulses. CONCLUSIONS: In some patients,
      the surface ECG pattern of atrial fibrillation is due to a focal rapidly firing
      source of activity that can be eliminated by discrete radiofrequency energy
      applications.

PMID- 9024142
TI  - Prospective study of moderate alcohol consumption and risk of peripheral arterial
      disease in US male physicians.
AB  - BACKGROUND: Moderate alcohol consumption decreases the risk of coronary heart
      disease, but its relation to peripheral arterial disease (PAD) is uncertain.
      METHODS AND RESULTS: In the Physicians' Health Study, a randomized trial of the
      use of aspirin and beta-carotene in 22071 apparently healthy men, we documented
      433 incident cases of PAD during 11 years of follow-up. After we controlled for
      age and treatment assignment, daily drinkers (> or = 7 drinks per week) had a
      relative risk (RR) of PAD of 0.92 (95% confidence interval, 0.72 to 1.17)
      compared with the reference group (< 1 drink per week). After additional control
      for smoking, however, the RR was 0.68 (0.52 to 0.89). Further control for
      exercise, diabetes mellitus, and parental history of myocardial infarction
      revealed an RR of 0.74 (0.57 to 0.97). CONCLUSIONS: Moderate alcohol consumption
      appears to decrease the risk of PAD in apparently healthy men.

PMID- 9024143
TI  - Baseline sodium-lithium countertransport and 6-year incidence of hypertension.
      The Gubbio Population Study.
AB  - BACKGROUND: Sodium-lithium countertransport (Na-Li CT) activity is high in
      persons with hypertension. This study investigated whether high Na-Li CT relates
      to development of hypertension. METHODS AND RESULTS: At the baseline visit of the
      Gubbio Population Study, 4210 people of the 5376 surveyed were 18 to 74 years
      old; of these, 1599 were hypertensive (systolic pressure > or = 140 mm Hg, or
      diastolic pressure > or = 90 mm Hg, or on antihypertensive drug therapy). Of the
      2611 nonhypertensives, 302 did not have Na-Li CT measured and 580 did not
      participate in 6-year follow-up. This analysis, therefore, deals with data
      collected on 1729 men 18 to 74 years old and women 18 to 74 years old who at
      baseline were nonhypertensive and had Na-Li CT measurement. Compared with
      individuals who were nonhypertensive at baseline and follow-up, individuals with
      incident hypertension at follow-up (systolic pressure > or = 140 mm Hg, or
      diastolic pressure > or = 90 mm Hg, or on antihypertensive drug therapy) had
      higher baseline values of Na-Li CT, blood pressure, age, body mass index, plasma
      cholesterol, and alcohol intake (P < .05). Baseline Na-Li CT was positively
      associated (P < .05) with development of hypertension in quartile analysis, with
      highest incidence of hypertension among men and women with Na-Li CT in the
      highest quartile (for men, > or = 376 and for women, > or = 311 mumol Li-L red
      blood cells-1.h-1). In univariate logistic regression, incidence of hypertension
      was related to baseline value of Na-Li CT, blood pressure, age, body mass index,
      plasma cholesterol, and alcohol intake (P < .05). In multiple logistic regression
      analysis, individuals with baseline Na-Li CT higher by 127 mumol (pooled SD for
      men and women) had 1.23 times greater risk of incident hypertension with control
      for sex and baseline age, body mass index, systolic pressure, and other
      confounders (P < .001). CONCLUSIONS: Na-Li CT is a predictor of hypertension risk
      in adults.

PMID- 9024144
TI  - Role of superoxide in angiotensin II-induced but not catecholamine-induced
      hypertension.
AB  - BACKGROUND: The major source of superoxide (.O2-) in vascular tissues is an
      NADH/NADPH-dependent, membrane-bound oxidase. We have previously shown that this
      oxidase is activated in angiotensin II-but not norepinephrine-induced
      hypertension. We hypothesized that hypertension associated with chronically
      elevated angiotensin II might be caused in part by vascular .O2- production.
      METHODS AND RESULTS: We produced hypertension in rats by a 5-day infusion of
      angiotensin II or norepinephrine. Rats were also treated with liposome
      encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was
      measured in conscious rats under baseline conditions and during bolus injections
      of either acetylcholine or nitroprusside. Vascular .O2- production was assessed
      by lucigenin chemiluminescence. In vitro vascular relaxations were examined in
      organ chambers. Norepinephrine infusion increased blood pressure to a similar
      extent as angiotensin II infusion (179 +/- 5 and 189 +/- 4 mm Hg, respectively).
      In contrast, angiotensin II-induced hypertension was associated with increased
      vascular .O2- production, whereas norepinephrine-induced hypertension was not.
      Treatment with liposome-encapsulated SOD reduced blood pressure by 50 mm Hg in
      angiotensin II-infused rats while having no effect on blood pressure in control
      rats or rats with norepinephrine-induced hypertension. Similarly, liposome
      encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in
      vitro responses to endothelium-dependent vasodilators in angiotensin II-treated
      rats. CONCLUSIONS: Hypertension caused by chronically elevated angiotensin II is
      mediated in part by .O2-, likely via degradation of endothelium-derived NO.
      Increased vascular .O2- may contribute to vascular disease in high
      renin/angiotensin II states.

PMID- 9024145
TI  - Tissue factor modulates the thrombogenicity of human atherosclerotic plaques.
AB  - BACKGROUND: The thrombogenicity of a disrupted atherosclerotic lesion is
      dependent on the nature and extent of the plaque components exposed to flowing
      blood together with local rheology and a variety of systemic factors. We
      previously reported on the different thrombogenicity of the various types of
      human atherosclerotic lesions when exposed to flowing blood in a well
      characterized perfusion system. This study examines the role of tissue factor in
      the thrombogenicity of different types of atherosclerotic plaques and their
      components. METHODS AND RESULTS: Fifty human arterial segments (5 foam cell-rich,
      9 collagen-rich, and 10 lipid-rich atherosclerotic lesions and 26 normal,
      nonatherosclerotic segments) were exposed to heparinized blood at high shear rate
      conditions in the Badimon perfusion chamber. The thrombogenicity of the arterial
      specimens was assessed by 111In-labeled platelets. After perfusion, specimens
      were stained for tissue factor by use of an in situ binding assay for factor
      VIIa. Tissue factor in specimens was semiquantitatively assessed on a scale of 0
      to 3. Platelet deposition on the lipid-rich atheromatous core was significantly
      higher than on all other substrates (P = .0002). The lipid-rich core also
      exhibited the most intense tissue factor staining (3 +/- 0.1 arbitrary units)
      compared with other arterial components. Comparison of all specimens showed a
      positive correlation between quantitative platelet deposition and tissue factor
      staining score (r = .35, P < .01). CONCLUSIONS: Our results show that tissue
      factor is present in lipid-rich human atherosclerotic plaques and suggest that it
      is an important determinant of the thrombogenicity of human atherosclerotic
      lesions after spontaneous or mechanical plaque disruption.

PMID- 9024146
TI  - Effects of cardiac allograft vasculopathy on myocardial blood flow, vasodilatory
      capacity, and coronary vasomotion.
AB  - BACKGROUND: Coronary vasculopathy is the third leading cause of death 1 year
      after cardiac allograft transplantation. This study was designed to assess the
      hemodynamic effects of transplant vasculopathy on myocardial blood flow and
      vasomotion. METHODS AND RESULTS: Thirty-two patients were studied 1 to 2 years
      after cardiac transplantation by use of positron emission tomography (n = 32),
      intravascular ultrasound (n = 26), coronary angiography (n = 32), and
      endomyocardial biopsy (n = 32). Twenty healthy individuals served as control
      subjects. Quantitative intravascular ultrasound was used to compute coronary
      lumen area, intimal thickness, and intimal index [Intima Area/(Intima + Lumen
      Area)]. Myocardial blood flow was quantified with the use of 13N-ammonia/positron
      emission tomography. Mean myocardial blood flow was higher in the transplant
      patients than in control subjects (0.94 +/- 0.26 versus 0.68 +/- 0.16 mL.min-1.g
      1 P < .0005). Cold increased myocardial blood flow to 0.79 +/- 0.18 mL.min-1.g-1
      in control subjects but not in patients (0.98 +/- 0.36 mL.g-1.min-1). Hyperemic
      myocardial blood flow was lower in patients than in control subjects (1.69 +/-
      0.78 versus 2.30 +/- 0.32 mL.min-1.g-1; P < .05) and was inversely related to
      maximal intimal thickness and intimal index (all P < .05). The myocardial flow
      reserve was reduced in patients (1.82 +/- 0.55 versus 3.45 +/- 1.03; P < .0001).
      CONCLUSIONS: The degree of intimal thickening is correlated with abnormalities in
      coronary function in patients with diffuse cardiac allograft vasculopathy. The
      reduction in vasodilatory capacity and the abnormal blood flow response to cold
      suggest abnormalities in endothelium-dependent and -independent coronary
      vasodilation in transplant recipients.

PMID- 9024147
TI  - Reduced coronary flow reserve during exercise in cardiac transplant recipients.
AB  - BACKGROUND: Coronary flow reserve (CFR) is reduced in a majority of patients
      after heart transplantation (HTx). Pharmacological interventions, however,
      provide only limited information on CFR under physiological conditions. Thus, CFR
      during exercise was evaluated in the present study. METHODS AND RESULTS: Coronary
      angiography was performed at rest and during supine bicycle exercise in 35
      patients early (2 to 3 months; n = 10) or late (1 to 6 years; mean, 2.5 years; n
      = 25) after HTx and in 8 controls (C). CFR was determined by parametric imaging
      after administration of 10 mg intracoronary papaverine, during exercise, and
      after 1.6 mg sublingual nitroglycerin. Epicardial coronary artery size was
      measured by quantitative coronary angiography. CFR after papaverine was normal
      early (3.6 +/- 0.5 versus C, 3.6 +/- 0.7; P = NS) and late (3.8 +/- 1.3 P = NS)
      after HTx. During exercise, CFR was normal early (3.1 +/- 0.6 versus C, 3.9 +/-
      0.9; P = NS) but decreased late (2.3 +/- 0.6; P < .01) after HTx. The increase in
      coronary cross-sectional area during exercise was also diminished late after HTx
      (14 +/- 10% versus C, 22 +/- 10%; P < .05). Both exercise-induced CFR (r = -.39,
      P < .05) and coronary vasodilation (r = -.44, P < .01) were inversely correlated
      with time after HTx. CONCLUSIONS: CFR during exercise is normal early but reduced
      late after HTx, whereas CFR after papaverine administration is maintained. This
      difference between physiological and pharmacological vasodilation suggests
      progressive endothelial dysfunction after HTx.

PMID- 9024148
TI  - In vitro effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3
      Fab on the activated clotting time.
AB  - BACKGROUND: In the evaluation of 7E3 for the Prevention of Ischemic Complications
      study (EPIC), the activated coagulation (clotting) times (ACTs) were longer in
      heparinized patients treated with c7E3 Fab than in those treated with placebo.
      The present study was designed to further investigate this observation by
      assessing whether the in vitro addition of c7E3 Fab to blood would affect the
      ACT. METHODS AND RESULTS: Native or heparinized blood obtained from normal
      volunteers was preincubated with antibodies c7E3 Fab (anti-GPIIb/IIIa and anti
      alpha v beta 3), 10E5 (anti-GPIIb/IIIa), or LM609 (anti-alpha v beta 3). The ACTs
      of the heparinized, but not native samples were significantly prolonged by the
      addition of c7E3 Fab and 10E5 but not LM609, indicating that the prolongation was
      due to GPIIb/IIIa blockade. The addition of c7E3 Fab also significantly prolonged
      the ACTs of blood anticoagulated with the direct thrombin inhibitors hirudin and
      D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone, indicating that the effect
      of c7E3 Fab was not exclusively related to decreased release of PF4, a heparin
      neutralizing factor, from platelets. CONCLUSIONS: These data support the
      conclusion that the prolongation of the ACT in patients in EPIC was due to c7E3
      Fab blockade of GPIIb/IIIa receptors. This raises the possibility that in vivo
      c7E3 Fab functions not only as an antiplatelet agent but also as an
      anticoagulant; direct in vivo data will, however, be required for assessment of
      this possibility.

PMID- 9024149
TI  - Hyperreactivity to nitrovasodilators in forearm vasculature is related to
      autonomic dysfunction in insulin-dependent diabetes mellitus.
AB  - BACKGROUND: The link between diabetes and vascular disease is poorly understood.
      Data regarding endothelial function in vivo in patients with insulin-dependent
      diabetes mellitus (IDDM) have been inconsistent with in vitro studies
      demonstrating hyperglycemia-induced impairments in endothelium-dependent
      vasodilation. METHODS AND RESULTS: We determined whether alterations in neural
      control of the vascular tone might contribute to blood flow responses to
      intrabrachial infusions of acetylcholine (ACh), sodium nitroprusside (SNP), and L
      N-monomethyl-arginine (L-NMMA) in 22 men with IDDM (12 with normoalbuminuria.
      HbA1c = 8.6 +/- 0.3%; 10 with macroalbuminuria, HbA1c = 8.6 +/- 0.3%) and 11
      matched normal men. Autonomic function was assessed from reflex vasoconstriction
      to cold, the blood pressure response to standing and hand grip, and heart rate
      variation, including spectral analysis, during controlled breathing, and the
      Valsalva maneuver. IDDM with macroalbuminuria exhibited hyperresponsiveness to
      both ACh and SNP compared with the patients with normoalbuminuria or normal
      subjects. Reflex sympathetic vasoconstriction to cold was severely impaired in
      the IDDM patients with macroalbuminuria (-19 +/- 6%) compared with
      normoalbuminuric patients (-39 +/- 5%, P < .05) and normal subjects (-54 +/- 7%,
      P < .001). The macroalbuminuric patients also had evidence of autonomic
      dysfunction during controlled and deep breathing tests and during the Valsalva
      maneuver. Within the group of IDDM patients, neither the urinary albumin
      excretion rate nor other parameters such as HbA1c or serum cholesterol correlated
      with forearm blood flow during the vasoactive drug infusions. There were,
      however, significant inverse correlations between several measures of both
      sympathetic and parasympathetic autonomic functions and vascular
      hyperresponsiveness to SNP and ACh. For example, the Valsalva ratio was inversely
      correlated with the increase in blood flow in response to infusion of 3 (r = 
      .74, P < .001) and 10 (r = -.73, P < .001) micrograms/min SNP and 7.5 (r = -.73,
      P < .001) and 15 (r = -.75, P < .001) micrograms/min ACh. CONCLUSIONS: These data
      are consistent with idea that altered neurotransmission is an important
      determinant of vascular reactivity of diabetic blood vessels to nitrovasodilators
      in vivo.

PMID- 9024150
TI  - Dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography
      in myocardial hibernation. Relation of contractile reserve to 201Tl uptake and
      comparative prediction of recovery of function.
AB  - BACKGROUND: The purposes of this study were to evaluate the comparative accuracy
      of dobutamine echocardiography and quantitative rest-redistribution 201Tl
      tomography in the prediction of recovery of function after revascularization and
      to assess the relation of contractile reserve to thallium uptake. METHODS AND
      RESULTS: Thirty-four patients with stable coronary disease and regional
      dysfunction underwent dobutamine echocardiography (2.5 up to 40 micrograms.kg
      1.min-1) and rest-redistribution 201Tl tomography 1 day before revascularization.
      Resting echocardiography and scintigraphy were repeated at > or = 6 weeks. Before
      revascularization, resting 201Tl uptake was similar in segments demonstrating
      biphasic or sustained improvement and was higher than in those exhibiting no
      change or worsening function during dobutamine. After revascularization, 201Tl
      uptake increased only in segments that showed a biphasic response (from 66 +/-
      12% to 78 +/- 13%; P < .05). Biphasic response had a sensitivity of 74% and
      specificity of 89% for prediction of recovery. The use of biphasic or sustained
      improvement responses increased the sensitivity to 86% with a decrease in
      specificity to 68%. Qualitative thallium assessment provided a high sensitivity
      (98%) but poor specificity (27%). Quantification of thallium uptake, however,
      improved its accuracy: a maximal uptake (at rest or redistribution) of > or = 60%
      yielded a 90% sensitivity and a 56% specificity. CONCLUSIONS: In patients with
      myocardial hibernation, biphasic response during dobutamine is less sensitive but
      more specific for recovery of function, whereas indexes of 201Tl scintigraphy are
      in general more sensitive and less specific, the least accurate being a
      qualitative assessment of thallium uptake. The sensitivity and specificity of
      both methods, however, can be altered depending on the quantitative criteria of
      thallium uptake or combination of responses of the myocardium to dobutamine.

PMID- 9024151
TI  - Assessment of mitral regurgitation severity by Doppler color flow mapping of the
      vena contracta.
AB  - BACKGROUND: Although Doppler color flow mapping is widely used to assess the
      severity of mitral regurgitation (MR), a simple, accurate, and quantitative
      marker of MR by color flow mapping remains elusive. We hypothesized that vena
      contracta width by color flow mapping would accurately predict the severity of
      MR. METHODS AND RESULTS: We studied 80 patients with MR. Vena contracta width was
      measured in multiple views with zoom mode and nonstandard angulation to optimize
      its visualization. Flow volumes across the left ventricular outflow tract and
      mitral annulus were calculated by pulsed-Doppler technique to determine
      regurgitant volume. Effective regurgitant orifice area was calculated by dividing
      the regurgitant volume by the continuous-wave Doppler velocity-time integral of
      the MR jet. The cause of MR was ischemia in 24, dilated cardiomyopathy in 34
      mitral valve prolapse in 12, endocarditis in 2, rheumatic disease in 2, mitral
      annular calcification in 1, and uncertain in 5. Regurgitant volumes ranged from 2
      to 191 mL. Regurgitant orifice area ranged from 0.01 to 1.47 cm2. Single-plane
      vena contracta width from the parasternal long-axis view correlated well with
      regurgitant volume (r = .85, SEE = 20 mL) and regurgitant orifice area (r = .86,
      SEE = 0.15 cm2). Biplane vena contracta width from apical views correlated well
      with regurgitant volume (r = .85, SEE = 19 mL) and regurgitant orifice area (r =
      .88, SEE = 0.14 cm2). A biplane vena contracta width > or = 0.5 cm was always
      associated with a regurgitant volume > 60 mL and a regurgitant orifice area > 0.4
      cm2. A biplane vena contracta width < or = 0.3 cm predicted a regurgitant volume
      < 60 mL and a regurgitant orifice area < 0.4 cm2 in 24 of 29 patients. No other
      parameter, including jet area, left atrial size, pulmonary flow reversal, or
      semiquantitative MR grade, correlated significantly with regurgitant volume or
      regurgitant orifice area in a multivariate analysis. CONCLUSIONS: Our results
      demonstrate that careful color flow mapping of the vena contracta of the MR jet
      provides a simple quantitative assessment of MR that correlates well with
      quantitative Doppler techniques.

PMID- 9024152
TI  - Increased airway pressure and simulated branch pulmonary artery stenosis increase
      pulmonary regurgitation after repair of tetralogy of Fallot. Real-time analysis
      with a conductance catheter technique.
AB  - BACKGROUND: Pulmonary regurgitation (PR) is an important determinant of outcome
      after repair of tetralogy of Fallot. Baseline PR was measured by magnetic
      resonance (MR) phase velocity mapping and from real-time right ventricular
      pressure-volume loops with a conductance catheter. Subsequently, the impact of
      two loading maneuvers (increased airway pressure, simulated branch pulmonary
      artery stenosis) on PR was assessed by the conductance catheter method. METHODS
      AND RESULTS: Thirteen patients, 3 to 35 years after tetralogy of Fallot repair or
      pulmonary valvotomy, had PR measured by MR phase velocity mapping while breathing
      spontaneously. During catheterization under general anesthesia. PR was estimated
      from right ventricular pressure-volume loops generated by conductance and
      microtip pressure catheters. The effect of increased airway pressure (continuous
      positive airway pressure, 20 cm H2O; n = 12) and simulated branch pulmonary
      artery stenosis (transient balloon occlusion of a branch pulmonary artery, n = 7)
      was measured. Basal PR fraction derived by MR and from right ventricular pressure
      volume loops had a correlation coefficient of .76 and mean of differences of 2.0
      +/- 18.2% (95% limits of agreement). Increased airway pressure increased PR (16.3
      +/- 11.4% to 25.7 +/- 17.3%, P < .01). Simulated branch pulmonary artery stenosis
      increased right ventricular end-systolic pressure (69.1 +/- 21.4 to 78.7 +/- 23.1
      mm Hg, P < .05) and PR (27.5 +/- 11.3% to 36.9 +/- 12.8%, P < .05). CONCLUSIONS:
      There was reasonable agreement between MR phase velocity-derived PR fraction and
      that obtained from right ventricular pressure-volume loops generated by use of
      conductance and pressure-microtip catheters. Exacerbation of PR by increased
      airway pressure and branch pulmonary stenosis may be relevant to the acute
      postoperative and long-term management, respectively, of patients after repair of
      tetralogy of Fallot.

PMID- 9024153
TI  - Incidence of induced atrial fibrillation/flutter in complete atrioventricular
      block. A concept of 'atrial-malfunctioning' atrio-hisian block.
AB  - BACKGROUND: Atrial fibrillation/flutter (Af) has been considered to occur
      coincidentally with atrioventricular (AV) block. However, a case with complete AV
      block was reported to histologically show fibrotic changes solely in the atrial
      muscles but neither in the AV node nor in the His bundle, indicating a possible
      relation between AV block and atrial tachyarrhythmias. To test a hypothesis that
      AV block and Af are causally interrelated, we investigated the incidence and
      electrophysiological characteristics of Af in complete AV block. METHODS AND
      RESULTS: Forty-two patients with persistent complete AV block underwent the
      electrophysiological study. Patients with spontaneous/electrically induced Af
      were compared with the other patients with respect to their electrophysiological
      variables. Of the 42 patients, Af was transiently induced by electrical
      stimulation in 5 patients (11.9%), while persistent Af was observed in 2 patients
      (4.8%, AH and HV block). AV block in the 5 patients with induced Af was
      invariably due to AH block. AH block complicated by persistent/induced Af was
      marked by relatively short RR intervals, significantly short junctional recovery
      time, and impaired intra-atrial conduction. CONCLUSIONS: Electrically induced Af
      in complete AV block was associated frequently with complete AH block. These
      patients were characterized differently from the commonly recognized AV block and
      therefore may stand as a unique subgroup of AH block.

PMID- 9024154
TI  - Low-molecular-weight tumor necrosis factor receptor p55 controls induction of
      autoimmune heart disease.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is involved in the
      pathogenesis of myocarditis and can bind to either tumor necrosis factor receptor
      (TNF-R) p55 or TNF-Rp75. However, it is not known which TNF-R mediates the
      specific functions of TNF in disease. To determine the role of the TNF/TNF-R
      system in chronic heart disease, we used a murine model of cardiac myosin-induced
      myocarditis that closely resembles the chronic stages of virus-induced
      myocarditis in humans. METHODS AND RESULTS: Mice lacking TNF-Rp55 expression
      after targeted disruption of the TNF-Rp55 gene were backcrossed into a genetic
      background susceptible to the induction of myocarditis with cardiac myosin. Here,
      we demonstrate that TNF-Rp55 gene-deficient mice did not develop any inflammatory
      infiltration into the heart after autoantigen injection, whereas control
      littermates showed autoimmune myocarditis at high prevalence and severity.
      Despite the absence of autoimmune heart disease, TNF-Rp55-/- mice produced
      cardiac myosin-specific IgG autoantibodies, indicating that activation of
      autoaggressive T and B lymphocytes had occurred. However, heart interstitial
      cells failed to express major histocompatibility complex (MHC) class II molecules
      in TNF-Rp55-/- animals, and adoptive transfer of autoreactive T cells resulted in
      heart disease only in TNF-Rp55-/- but not in TNF-Rp55-/- littermates.
      CONCLUSIONS: Cardiac myosin-induced myocarditis is dependent on autoaggressive T
      cells and on autoantigen presentation in association with MHC class II molecules
      within the heart. Thus, lack of TNF-Rp55 expression could interfere with either
      lymphocyte activation or target organ susceptibility. The data presented here
      show that the TNF-Rp55 is a key regulator for the induction of autoimmune heart
      disease by its controlling target organ susceptibility.

PMID- 9024155
TI  - L-arginine reduces human monocyte adhesion to vascular endothelium and
      endothelial expression of cell adhesion molecules.
AB  - BACKGROUND: Monocyte adhesion to endothelial cells is a key early event in
      atherogenesis. Because L-arginine has been shown to reduce atheroma and to
      decrease monocyte-endothelial cell adhesion in an animal model of
      atherosclerosis, we studied the effects of L-arginine on human monocyte adhesion
      to human endothelial cells and endothelial expression of cell adhesion molecules.
      METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were grown
      to confluence, then incubated for 24 hours with arginine-deficient media to which
      was added saline (control), 100 or 1000 mumol/L L-arginine, 100 mumol/L D
      arginine, 100 mumol/L NG-monomethyl-L-arginine (L-NMMA), or 100 mumol/L L
      arginine with 100 mumol/L L-NMMA. Human monocytes obtained by elutriation were
      incubated for 1 hour with HUVECs, and adhesion was measured by light microscopy.
      Compared with control, monocyte adhesion was reduced by L-arginine (59 +/- 10%, P
      = .01) and increased by L-NMMA (123 +/- 20%, P = .01). Surface expression of cell
      adhesion molecules by HUVECs was assessed by an ELISA under the above conditions
      with and without stimulation with interleukin-1 beta. Expression of ICAM-1 was
      reduced with both concentrations of L-arginine compared with control in both the
      basal (43 +/- 12%, P < .01), and stimulated (46 +/- 15%, P < .01) states, which
      correlated with decreased levels of mRNA. Expression of VCAM-1 was reduced only
      in the stimulated state and only in the presence of 1000 mumol/L L-arginine (72
      +/- 24%, P = .02). CONCLUSIONS: L-Arginine reduces human monocyte adhesion to
      endothelial cells and decreases expression of certain endothelial cell adhesion
      molecules.

PMID- 9024156
TI  - Antisense oligonucleotide inhibition of PDGFR-beta receptor subunit expression
      directs suppression of intimal thickening.
AB  - BACKGROUND: The elucidation of molecular mechanisms of vascular cell biology has
      markedly influenced our thinking on the pathophysiology of vascular disease.
      Antisense oligonucleotide gene therapy has helped identify proteins critical to
      cell-cycle progression and proliferation and possible therapeutic strategies to
      combat human disease. This approach, however, has not yet been used to examine
      the contribution of chemotactic proteins and/or their receptors. Platelet-derived
      growth factor-BB (PDGF-BB) released from activated platelets adherent to
      subendothelial connective tissue is a principal smooth muscle cell chemotactic
      factor. METHODS AND RESULTS: A series of experiments was performed to assess the
      capacity of antisense oligonucleotides to reduce PDGF-beta receptor subunit
      (PDGFR-beta) expression and the contribution of PDGFR-beta in neointimal
      formation. Sustained, direct, and local perivascular administration of two
      different antisense oligonucleotide sequences complementary to PDGFR-beta mRNA
      almost completely abolished the expression of PDGFR-beta protein in the intima
      and media of injured carotid arteries and decreased neointimal formation by 80%
      and 60%, respectively. Furthermore, neointimal formation correlated precisely
      with PDGFR-beta expression in an exponential fashion. CONCLUSIONS: Thus,
      myointimal proliferation depends on both PDGFR-beta overexpression and its
      activation by PDGF-BB. Removal of either of these two elements can suppress
      neointimal formation.

PMID- 9024157
TI  - Attenuation by gemfibrozil of expression of plasminogen activator inhibitor type
      1 induced by insulin and its precursors.
AB  - BACKGROUND: Insulin and its precursors found in increased plasma concentrations
      in non-insulin-dependent diabetes mellitus (NIDDM) augment synthesis of
      plasminogen activator inhibitor type 1 (PAI-1) in Hep G2 cells in vitro and in
      rabbit liver in vivo. Reduced endogenous fibrinolysis secondary to increased PAI
      1 activity may exacerbate atherogenesis. Recently, the reduction of the coronary
      heart disease incidence in the Helsinki Heart Study has implicated favorable
      modulation of endogenous fibrinolysis by gemfibrozil. METHODS AND RESULTS: In Hep
      G2 cells, 500 (700) mumol/L gemfibrozil decreased basal secretion of PAI-1 by 26%
      (43%) (P = .012 and P = .021, respectively) and attenuated insulin-induced (10
      nmol/L) augmentation of PAI-1 in conditioned media by 61% (109%) (P = .010)
      within 24 hours. Inhibition was dependent on the duration of exposure (0 to 48
      hours) and on the concentration of gemfibrozil (0 to 700 mumol/L) but not on the
      concentration of insulin (0.1 to 100 nmol/L). Gemfibrozil attenuated the
      augmentation of PAI-1 secretion induced by proinsulin (> 100%), by
      des(31,32)proinsulin (75%), and by des(64,65) proinsulin (77%) as well (10 nmol/L
      each). The specificity of these effects was confirmed by the unaltered levels of
      newly synthesized protein (metabolic labeling) and of total protein (both in
      conditioned media and cell lysates). Secretion of fibrinogen by Hep G2 cells was
      not affected by gemfibrozil. Changes in PAI-1 protein levels reflected modulation
      of PAI-1 gene expression as manifested by changes in levels of 3.2-kb PAI-1 mRNA
      (Northern blots). CONCLUSIONS: Gemfibrozil attenuated the augmentation of
      synthesis and secretion of PAI-1 induced by insulin and its precursors directly
      and specifically. Accordingly, gemfibrozil may exert favorable therapeutic
      effects normalizing impaired fibrinolysis in patients with hyperinsulinemia such
      as NIDDM.

PMID- 9024158
TI  - Complement C5a, TGF-beta 1, and MCP-1, in sequence, induce migration of monocytes
      into ischemic canine myocardium within the first one to five hours after
      reperfusion.
AB  - BACKGROUND: Recent studies suggest that reperfusion promotes healing of formerly
      ischemic heart tissue even when myocardial salvage is no longer possible. Since
      monocyte-macrophage infiltration is the hallmark of the healing infarct, we have
      attempted to identify mechanisms that attract monocytes into the heart after
      reperfusion of ischemic canine myocardium. METHODS AND RESULTS: Isolated
      autologous 99mTc-labeled mononuclear leukocytes injected into the left atrium
      localized preferentially in previously ischemic myocardium within the first hour
      after reperfusion. Histological studies revealed CD64+ monocytes in small venules
      and the perivascular connective tissue within the first hour after reperfusion.
      Flow cytometric analysis of cells in cardiac lymph showed systematically
      increasing numbers of neutrophils and monocytes between 1 and 4 hours after
      reperfusion; monocyte enrichment was eventually greater than neutrophil
      enrichment. Monocyte chemotactic activity in cardiac lymph collected in the first
      hour after reperfusion was wholly attributable to C5a. Transforming growth factor
      (TGF)-beta 1 contributed significantly to this chemotactic activity after 60 to
      180 minutes, and after 180 minutes, monocyte chemotactic activity in lymph was
      largely dependent on monocyte chemoattractant protein (MCP)-1 acting in concert
      with TGF-beta 1. CONCLUSIONS: Beginning in the first 60 minutes after
      reperfusion, C5a, TGF-beta 1, and MCP-1, acting sequentially, promote
      infiltration of monocytes into formerly ischemic myocardium. These events may
      promote the healing of myocardial injury facilitated by reperfusion.

PMID- 9024159
TI  - Induction of monocyte chemoattractant protein-1 in the small veins of the
      ischemic and reperfused canine myocardium.
AB  - BACKGROUND: Healing after myocardial infarction is characterized by the presence
      of macrophages in the infarcted area. Since augmented monocyte influx has been
      implicated as a potential mechanism for improved healing after reperfusion, we
      wished to study the induction of monocyte chemoattractant protein-1 (MCP-1)
      during reperfusion. METHODS AND RESULTS: The cDNA for MCP-1 was cloned from a
      canine jugular vein endothelial cell (CJVEC) library and exhibited 78% identity
      with the deduced amino acid sequence of human MCP-1. Samples of myocardium were
      taken from control and ischemic segments after 1 hour of ischemia and various
      times of reperfusion; total RNA was isolated from myocardial samples and probed
      with a cDNA probe for canine MCP-1. Induction of MCP-1 mRNA occurred only in
      previously ischemic segments within the first hour of reperfusion, peaked at 3
      hours, and persisted throughout the first 2 days of reperfusion. In the absence
      of reperfusion, no significant MCP-1 induction was seen. Both ischemic (but not
      preischemic) cardiac lymph and human recombinant TNF-alpha induced MCP-1 in
      CJVECs. MCP-1 was identified by immunostaining on infiltrating cells and venular
      (but not arterial) endothelium by 3 hours. In contrast, in situ hybridization
      showed MCP-1 mRNA to be confined to the endothelium of small veins (venules) 10
      to 70 microns in diameter. CONCLUSIONS: MCP-1 mRNA is induced in the endothelium
      of a specific class of small veins immediately after reperfusion. MCP-1 induction
      is confined to the previously ischemic area that has been reperfused. We suggest
      a significant role for MCP-1 in monocyte trafficking in the reperfused
      myocardium.

PMID- 9024160
TI  - Intracoronary application of C1 esterase inhibitor improves cardiac function and
      reduces myocardial necrosis in an experimental model of ischemia and reperfusion.
AB  - BACKGROUND: Myocardial injury from ischemia can be aggravated by reperfusion of
      the jeopardized area. The precise underlying mechanisms have not been clearly
      defined, but proinflammatory events, including complement activation, leukocyte
      adhesion, and infiltration and release of diverse mediators, probably play
      important roles. The present study addresses the possibility of reducing
      reperfusion damage by the application of C1 esterase inhibitor (C1-INH). METHODS
      AND RESULTS: Cardioprotection by C1-INH 20 IU/kg IC was examined in a pig model
      with 60 minutes of coronary occlusion, followed by 120 minutes of reperfusion. C1
      INH was administered during the first 5 minutes of coronary reperfusion Compared
      with the NaCl controls, C1-INH reduced myocardial injury (48.8 +/- 7.8% versus
      73.4 +/- 4.0% necrosis of area at risk, P < or = .018). C1-INH treatment
      significantly reduced circulating C3a and slightly attenuated C5a plasma
      concentrations. Myocardial protection was accompanied by reduced plasma
      concentration of creatine kinase and troponin-T. C1-INH had no effect on global
      hemodynamic parameters, but local myocardial contractility was markedly improved
      in the ischemic zone. In the short-axis view, 137 degrees of the anteroseptal
      region showed significantly improved wall motion at early and 29 degrees at late
      reperfusion with C1-INH treatment. CONCLUSIONS: C1-INH significantly protects
      ischemic tissue from reperfusion damage, reduces myocardial necrosis, and
      improves local cardiac function.

PMID- 9024161
TI  - Long-term estradiol replacement decreases contractility of guinea pig coronary
      arteries to the thromboxane mimetic U46619.
AB  - BACKGROUND: Estradiol replacement therapy reduces the incidence of coronary
      artery disease. Current evidence suggests that estradiol may stimulate the
      production of endothelium-derived NO and thereby reduce the contractile response
      of vascular smooth muscle. We investigated the effect of long-term replacement of
      estradiol on NO release and its effect on coronary artery contractility. METHODS
      AND RESULTS: Female guinea pigs were ovariectomized and allowed to recover for
      100 days. Pellets containing 17 beta-estradiol (0.25, 0.5, 1.5, and 7.5 mg
      released over 21 days) were placed subcutaneously for 19 to 20 days. Animals were
      then anesthetized, and the coronary arteries were excised and cut into ring
      segments. Rings were placed in small-vessel myographs for measurement of
      isometric force. Contractile responses of coronary arteries to cumulative
      addition of U46619 (10(-10) to 10(-5) mol/L), a thromboxane mimetic, were
      measured in the presence and absence of nitro-L-arginine (LNA), a selective NO
      synthase inhibitor, and methylene blue, a guanylate cyclase inhibitor. Low (0.25
      mg) but not high (0.5-, 1.5-, or 7.5-mg) doses of estradiol inhibited the maximal
      contractile responses to U46619 compared with arteries from untreated castrated
      animals. In addition, both LNA and methylene blue potentiated contractile
      responses to U46619 of arteries from animals receiving 0.25 and 0.5 mg but not
      1.5 and 7.5 mg estradiol. Negative log EC50 values were significantly inhibited
      at 0.25 and 7.5 mg but unaffected at 0.5 and 1.5 mg estradiol compared with
      castrated animals. CONCLUSIONS: Estradiol at low doses may protect against
      vasospasm by stimulating endothelium-derived NO release and inhibiting coronary
      artery contractility.

PMID- 9024162
TI  - A tissue plasminogen activator/P-selectin fusion protein is an effective
      thrombolytic agent.
AB  - BACKGROUND: P-selectin is expressed on the surface of activated endothelial cells
      and platelets. We hypothesized that a tissue plasminogen activator (TPA)/P
      selectin fusion protein would have not only thrombolytic activity but also might
      target TPA to the thrombi. In addition, it seemed possible that this chimeric
      protein would competitively inhibit the binding of native P-selectin on
      endothelial cells and platelets to leukocytes and thus further promote
      thrombolysis. METHODS AND RESULTS: The full-length, plasminogen activator
      inhibitor-1-resistant form of TPA (TPAIR) together with two TPAIR/P-selectin
      fusion constructs (P280IR and P121IR) were expressed with the use of baculovirus
      vectors. After infection of Sf21 cells with the recombinant baculovirus,
      recombinant TPAIR and P-selectin/TPAIR fusion proteins were purified with the use
      of metal ion chromatography. The intact protease activity of TPAIR and the ligand
      binding capability of P-selectin were confirmed through indirect chromogenic and
      cell binding assays, respectively. These molecules were assessed both in vitro
      and in vivo for thrombolytic activity. In vitro clot lysis assays indicated equal
      efficacy of TPAIR, P280IR, and P121IR (P > .5). The in vivo efficacy was tested
      in a cyclic flow variation model with the use of the rat mesenteric artery.
      Compared with saline control treatment, reduction in cyclic flow variations was
      significant (P < .05) and similar (P > .5) among TPAIR, P280IR, and P121IR. No
      significant bleeding was noted among treated animals. CONCLUSIONS: Chimeric
      proteins P280IR and P121IR have clot lysis activities that are similar to TPAIR
      both in vitro and in vivo. These chimeric proteins also bind to P-selectin ligand
      in vitro. Thus, these proteins may provide an efficient method of targeting TPA
      to the thrombotic region. Further experimental analysis with the use of larger
      animal coronary occlusion models should help determine the future value of these
      proteins as clinical therapeutic agents.

PMID- 9024163
TI  - Inhibitors of arterial relaxation among components of human oxidized low-density
      lipoproteins. Cholesterol derivatives oxidized in position 7 are potent
      inhibitors of endothelium-dependent relaxation.
AB  - BACKGROUND: Oxidized low-density lipoproteins (LDLs) are known to impair arterial
      relaxation. The aim of the present study was to identify the components of
      oxidized LDL that may account for inhibition of endothelium-dependent relaxation.
      METHODS AND RESULTS: LDLs from 12 healthy subjects were either maintained at 4
      degrees C (native LDL) or incubated at 37 degrees C in the presence of copper
      sulfate (oxidized LDL). Unlike pretreatment with native LDL, pretreatment with
      oxidized LDL reduced significantly the acetylcholine-mediated relaxation of
      rabbit aortic segments compared with control segments incubated in Krebs' buffer
      (maximal relaxation [Emax], 72.0 +/- 6.7% versus 94.1 +/- 0.8%, respectively, P <
      .01; negative logarithm of the concentration required to produce a half-maximal
      relaxing effect [pD2], 6.6 +/- 0.1 versus 7.2 +/- 0.1, respectively, P < .001).
      The absolute difference between Emax values obtained with oxidized and native LDL
      (delta Emax) correlated significantly with the formation of 7 ketocholesterol, 7
      alpha-hydroxycholesterol, and 7 beta-hydroxy-cholesterol. In contrast, delta Emax
      did not correlate with the amount of lipoperoxides or lysophosphatidylcholine
      formed, and the difference of pD2 values measured with oxidized and native LDL
      (delta pD2) did not correlate significantly with any of the oxidation-derived LDL
      compounds. When added individually, 7-ketocholesterol and 7 beta
      hydroxycholesterol reduced Emax values but not pD2 values in a time- and
      concentration-dependent manner. CONCLUSIONS: Cholesterol derivatives in oxidized
      LDL can reduce maximal arterial relaxation through a specific effect on vascular
      endothelial cells.

PMID- 9024164
TI  - Effects of MCI-154, a calcium sensitizer, on left ventricular systolic and
      diastolic function in pacing-induced heart failure in the dog.
AB  - BACKGROUND: MCI-154 is a positive inotropic agent that increases the myofilament
      response to Ca2+. Whether MCI-154 has beneficial effects on left ventricular
      dysfunction in chronic heart failure is not known. We examined the effects of MCI
      154 on left ventricular systolic and diastolic function in pacing-induced heart
      failure in dogs. METHODS AND RESULTS: We studied eight anesthetized dogs before
      and 2 to 4 weeks after rapid right ventricular pacing. Left cineventriculograms
      with simultaneous left ventricular pressures (tip manometer) were obtained before
      and during intravenous administration of MCI-154 (I.O. microgram.kg-1.min-1 for
      15 minutes) in the control and heart-failure states. Left ventricular volume
      dynamics was derived from frame-by-frame (20-ms) analyses of left ventricular
      angiograms. In heart failure, left ventricular contractility as assessed by
      shifts of the end-systolic pressure-volume ratio, evaluated by inferior vena cava
      occlusion, was improved by MCI-154 (+ 1.94 mm Hg/mL, P < .05) to an extent
      similar to that in the control state (+2.47 mm Hg/mL, P < .05). MCI-154 also
      accelerated left ventricular relaxation, assessed by the time constant of
      isovolumic pressure decay (T1/2), in both states. The absolute decrease in T1/2
      with MCI-154 in heart failure was significantly greater than in the control state
      (-8.2 versus -3.1 ms, P < .05). In heart failure, MCI-154 shifted the left
      ventricular diastolic pressure-volume relation clearly downward, suggesting
      increased diastolic distensibility. CONCLUSIONS: MCI-154 improved not only left
      ventricular systolic function but also diastolic relaxation and distensibility in
      a chronic heart failure model.

PMID- 9024165
TI  - Academic cardiology division in the era of managed care. A paradigm for survival.
AB  - The ability of academic divisions of cardiology to pursue educational and
      research missions in an era of market-driven managed care is being increasingly
      jeopardized. Indeed, several academic medical centers have been sold to for
      profit entities, and many cardiology divisions have been forced to decrease staff
      and faculty reimbursements. Despite these threats, the academic division has
      unique strengths: (1) premium quality of care, (2) a single employer, (3) a
      somewhat uniform practice culture, (4) high-volume operators performing
      interventional procedures, (5) expertise in highly technical aspects of
      cardiology, and (6) the availability of physicians for outreach ventures.
      Therefore, we hypothesized that the cardiology division could be strengthened by
      collaborating with the medical center in the development of an aggressive and
      proactive managed care strategy. To this end, we developed a cardiovascular
      network having the academic center as its central focus but including a group of
      high-quality and geographically dispersed community-based physicians. These
      physicians were attracted by an economic package that provided protection from
      downside risk, participation in our managed care initiatives, and geographic
      exclusivity in an over-crowded market. In turn, the community-based physicians
      increasingly used the academic medical center for tertiary care, resulting in
      increased volumes and incremental profitability. Using this paradigm, we have now
      recruited approximately 40 community cardiologists. The resulting network
      provides access to a university cardiologist in most of the surrounding urban and
      rural counties and will allow us to compete effectively for capitated contracts.

PMID- 9024167
TI  - Images in cardiovascular medicine. Impending paradoxical embolus.

PMID- 9024166
TI  - Relaxation-systolic pressure relation. A load-independent assessment of left
      ventricular contractility.
AB  - This contribution reviews the regulation of left ventricular pressure (LVP) fall
      by load and relates this regulation to left ventricular contractility. Load
      regulation of LVP fall has to be distinguished from neurohumoral regulation, from
      effects induced by arterial reflected waves and from long-term load effects on
      contractility. The response of LVP fall to a moderate elevation of systolic LVP
      is highly variable. It depends on the ratio between the actual systolic pressure
      and peak isovolumetric pressure, defined as "relative load". Up to a relative
      load of 81% to 84%, LVP fall accelerates. Above this relative load, LVP fall
      decelerates. Depending on the level of relative load there is a wide variety of
      effects ranging from moderate acceleration of LVP fall to marked deceleration of
      LVP fall. Acceleration of LVP fall in response to a load elevation is associated
      with normal cardiac function, while slowing of LVP fall is associated with
      impaired cardiac function. Similar but opposite effects are observed with
      reductions of systolic LVP. Effects of changes in systolic LVP on time constant
      tau reveal a fair correlation with systolic elastance (Ees), peak dP/dtmax and
      regional fractional shortening (or ejection fraction). There is an excellent
      correlation with measured isovolumetric LVP, indicating that contraction
      relaxation coupling is close when contractility is expressed in terms of peak
      isovolumetric pressure. Assessment of contractility with systolic LVP-relaxation
      relation is precise and load independent and can be performed with the sole use
      of a high-fidelity pressure gauge positioned in the left ventricular cavity.

PMID- 9024168
TI  - Implementation of multiple outpatient formularies: undesirable effects.

PMID- 9024169
TI  - Triazolam is ineffective in patients taking rifampin.
AB  - BACKGROUND: Triazolam is metabolized predominantly by cytochrome P450 3A4
      (CYP3A4). Rifampin (rifampicin) is a potent inducer of CYP3A4 and it is known to
      markedly reduce plasma concentrations and effects of drugs such as midazolam. The
      possible interaction between rifampin and triazolam was examined in this study.
      METHODS: The pharmacokinetics and pharmacodynamics of triazolam were investigated
      in a randomized, double-blind crossover study with two phases. Ten young healthy
      volunteers took either 600 mg rifampin once daily or placebo for 5 days. On the
      sixth day, 0.5 mg triazolam was administered orally. Timed blood samples were
      collected and the effects of triazolam were measured with five psychomotor tests
      for 10 hours. RESULTS: The area under the plasma triazolam concentration-time
      curve in the rifampin phase was only 5.1% of that in the placebo phase (0.74 +/-
      0.14 versus 14.8 +/- 1.0 ng.hr/ml [mean +/- SEM; p < 0.001]). Rifampin
      pretreatment decreased the maximum plasma concentration of triazolam to 12.4% of
      the control value (i.e., from 2.9 +/- 0.2 to 0.36 +/- 0.06 ng/ml [p < 0.001]) and
      the elimination half-life from 2.8 +/- 0.1 to 1.3 +/- 0.1 hours (p < 0.001). All
      psychomotor tests showed markedly reduced effects (p < 0.01) of triazolam after
      rifampin pretreatment. CONCLUSIONS: Triazolam is ineffective during rifampin
      treatment. This is most likely due to increased metabolism of triazolam after
      induction of CYP3A4 in the gut wall and liver by rifampin. It is advisable to use
      hypnotic agents that are not metabolized by CYP3A4 during treatment with rifampin
      or other potent inducers of CYP3A4.

PMID- 9024170
TI  - Effects of liver disease on the disposition of the opioid antagonist nalmefene.
AB  - OBJECTIVES: The pharmacokinetics of nalmefene and its glucuronide metabolite were
      investigated in 12 patients with liver disease (four patients with mild, five
      patients with moderate, and three patients with severe liver disease) and 12 age
      , weight-, and gender-matched control subjects. METHODS: Subjects received a
      single intravenous bolus 2.0 mg dose of nalmefene. Multiple blood and urine
      samples were collected for 48 hours. Within 1 week of nalmefene administration,
      antipyrine and galactose clearances were determined as general markers of hepatic
      metabolism and effective liver plasma flow, respectively. Plasma concentrations
      of nalmefene were determined by radioimmunoassay. RESULTS: The antipyrine and
      galactose clearance values were 56% and 33% lower, respectively, in the patients
      with liver disease compared with the normal healthy control subjects. The
      systemic clearance of nalmefene was reduced by 32% (0.61 +/- 0.21 versus 0.90 +/-
      0.27 L/hr/kg [mean +/- SD]) and the terminal elimination half-life was increased
      by 31% (10.5 +/- 1.9 versus 8.0 +/- 2.2 hours) in the patients with liver
      disease. This was primarily the result of a 31% reduction (0.181 +/- 0.067 versus
      0.263 +/- 0.072 L/hr/kg) in nalmefene glucuronide formation clearance. There were
      no significant differences in nalmefene volumes of distribution or protein
      binding. There was a significant inverse relationship between nalmefene clearance
      and Pugh score (r = -0.57; p = 0.004), indicating decreasing nalmefene clearance
      with increasing severity of liver disease. CONCLUSIONS: The clearance of
      nalmefene was significantly reduced in the presence of liver disease. However,
      because nalmefene will be primarily used in the acute care setting for reversal
      of opioid-induced effects, it is not likely that these alterations will
      necessitate a dosage modification.

PMID- 9024171
TI  - Influence of polymorphic N-acetyltransferase phenotype on the inhibition and
      induction of acetaminophen bioactivation with long-term isoniazid.
AB  - OBJECTIVE: To determine in patients receiving isoniazid prophylaxis whether an
      increase in the CYP2E1 dependent formation clearance of acetaminophen
      (paracetamol) to N-acetyl-p-benzoquinone imine (NAPQI) occurs during a normal 24
      hour isoniazid dose interval and whether the interaction is dependent on
      acetylation status. METHODS: Acetaminophen elimination kinetics were determined
      on four different occasions. Ten subjects were assigned to receive acetaminophen
      either simultaneously with the 8 am dose of isoniazid or 12 hours after the
      isoniazid dose. One week later, on the last day of isoniazid therapy, subjects
      received acetaminophen at the alternate time of day. The control phase
      acetaminophen administrations were repeated 1 and 2 weeks later, following the
      initial randomization. Isoniazid acetylation (NAT2) genotype was determined by
      analysis of genomic DNA obtained from peripheral blood leukocytes. RESULTS: The
      mean NAPQI formation clearance was inhibited 57% when acetaminophen and isoniazid
      were coadministered but was unchanged compared with time-matched control when
      acetaminophen was given 12 hours after the isoniazid dose. However, when data
      from subjects was segregated according to isoniazid (INH) acetylation phenotype,
      the mean ratio of NAPQI formation clearances (+INH/-INH) with 8 PM acetaminophen
      was significantly higher for fast acetylators compared with slow acetylators
      (1.36 versus 0.68; p = 0.006). CONCLUSIONS: Fast metabolizers of isoniazid
      appeared to clear the inducer or inhibitor from the active site of CYP2E1 more
      rapidly, which resulted in an increased formation of NAPQI 12 hours after the
      isoniazid dose. In contrast, formation of NAPQI for slow isoniazid metabolizers
      remained inhibited.

PMID- 9024172
TI  - The effect of valsartan on the angiotensin II pressor response in healthy
      normotensive male subjects.
AB  - OBJECTIVE: Valsartan is an oral antagonist of angiotensin II that competes with
      angiotensin II for the AT1-receptor and is being developed as an antihypertensive
      agent. This study assessed the ability of 80 mg valsartan to inhibit the pressor
      effect of exogenous angiotensin II in healthy normotensive men, first after a
      single dose and then after multiple doses once daily for 7 days. METHODS: This
      was a single-center, double-blind, placebo-controlled, randomized crossover
      study. Six healthy men underwent angiotensin II challenges to determine a
      suitable dose required to increase their systolic blood pressure by approximately
      30 mm Hg. Each subject then received an 80 mg dose of valsartan or matching
      placebo. The inhibition of the angiotensin II pressor effect was determined by
      the systolic blood pressure response to repeated angiotensin II challenges at
      multiple time points. RESULTS: Systolic blood pressure responses to angiotensin
      II challenges after single and multiple doses of valsartan were significantly
      lower than placebo, indicating that valsartan blocked the blood pressure response
      to angiotensin II. The maximum blocking effect was observed within 2 to 3 hours.
      Mean data suggested that differences in effect between valsartan and placebo were
      similar after both single and multiple doses and persisted up to 24 hours after
      administration. The angiotensin II blocking effect was maintained up to this
      time, despite low plasma valsartan levels and minimal accumulation after multiple
      doses. CONCLUSION: Valsartan, 80 mg, is a potent angiotensin II antagonist with a
      rapid onset of action and persistent angiotensin II inhibition up to 24 hours.
      There is no attenuation of this effect after multiple doses.

PMID- 9024173
TI  - A comparison of spectral edge, delta power, and bispectral index as EEG measures
      of alfentanil, propofol, and midazolam drug effect.
AB  - BACKGROUND: The effects of anesthetic drugs on electroencephalograms (EEG) have
      been studied to develop the EEG as a measure of anesthetic depth. Bispectral
      analysis is a new quantitative technique that measures the consistency of the
      phase and power relationships and returns a single measure, the bispectral index.
      The purpose of this study was to compare the performance of the bispectral index,
      version 1.1, with other spectral analysis EEG measures of drug effect for three
      commonly used anesthetic drugs. METHODS: The EEG waveforms from 31 adults
      receiving infusions of alfentanil, propofol, or midazolam were analyzed. The time
      course of spectral edge (SE95), relative power in delta band, and bispectral
      index were related to the estimated effect-site concentration with use of a
      sigmoidal Emax model to estimate the potency (IC50) and the plasma effect-site
      equilibration rate constant (Ke0) for each measure. The performance of the
      fitting was assessed by the coefficient of correlation between predicted and
      observed effect. RESULTS: Alfentanil induced a high-amplitude low-frequency EEG
      response. Propofol induced a biphasic response. At low concentrations, both
      frequency and amplitude increased. When the concentration increased, the EEG
      slowed and the amplitude decreased. High concentration produced burst
      suppression. Midazolam increased EEG frequency and amplitude. Bispectral index,
      SE95, and delta power yield similar estimates of IC50 and ke0. Except for
      alfentanil, the performance of the modeling with the bispectral index was as good
      that with SE95 or delta power. CONCLUSION: Bispectral analysis can be used as a
      measure of the EEG effects of anesthetic drugs.

PMID- 9024174
TI  - DuP 532, an angiotensin II receptor antagonist: first administration and
      comparison with losartan.
AB  - We investigated the tolerability and angiotensin II antagonist activity of oral
      DuP 532 in healthy male subjects. DuP 532 (1 to 200 mg) was well tolerated, with
      no effect on blood pressure or heart rate. Compared with losartan (100 mg), DuP
      532 (200 mg) was a weak antagonist of pressor responses to intravenous
      angiotensin II. Maximum inhibition of diastolic pressor response was 86% (95%
      confidence interval [CI], 84%, 88%) approximately 4.6 hours after losartan and
      48% (95% CI, 38%, 56%) 8.7 hours after DuP 532. Twenty-four hours after dosing,
      inhibition by losartan and DuP 532 was similar (40% to 45%). DUP 532 is
      extensively bound in human plasma, with an in vitro free fraction of 0.06.
      Although DuP 532 and EXP3174 (losartan's active metabolite) have similar AT1
      receptor potency, and plasma concentrations of DuP 532 were much greater than
      losartan/EXP3174, the level of antagonism was much less for DuP 532. These
      results indicate that multiple factors determine the in vivo potency of
      angiotensin II antagonists, including affinity for and distribution to the
      receptor as modulated by plasma binding.

PMID- 9024175
TI  - A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in
      patients with AIDS and AIDS-related complex.
AB  - INTRODUCTION: This article reports a meta-analysis focused on the efficacy of
      zalcitabine and zidovudine alone or in combination as reported by three AIDS
      Clinical Trial Group trials. We analyzed the log CD4 count (LCD4) response to
      therapy up to 1 year after the beginning of therapy. One of the purposes of this
      article was to illustrate a meta-analysis method that permits pooling of original
      data from trials with different designs. METHODS: To effectively eliminate
      obvious differences due to design, we first estimated complete (1 year)
      individual LCD4 versus time curves using a sophisticated smoothing technique.
      Then several summary descriptors were computed from the completed LCD4 curves.
      Those descriptors were corrected for baseline covariate differences, and the
      corrected values were then related to measures of drug exposure. RESULTS:
      Significant baseline covariates were LCD4 baseline count and AIDS-related complex
      or AIDS diagnosis. The predictor, corrected for baseline covariates, that
      correlated best with drug exposure was intensity, the initial rate of rise of
      LCD4, estimated as the slope of LCD4 between pretreatment and peak LCD4.
      CONCLUSION: Using intensity as a single response measure, we found weak evidence
      for synergism of zalcitabine and zidovudine: combination therapy increased
      response by 20% over that expected from a purely additive interaction.

PMID- 9024176
TI  - Montelukast causes prolonged, potent leukotriene D4-receptor antagonism in the
      airways of patients with asthma.
AB  - Montelukast, a new specific oral cysteinyl LT3-receptor antagonist was evaluated
      for its activity in attenuating inhaled leukotriene D4 (LTD4) bronchoconstriction
      in patients with asthma. In two double-blind, placebo-controlled, randomized
      crossover studies, patients with mild asthma (forced expiratory volume in 1
      second [FEV1] > or = 70%) were studied. In trial A, LTD4 challenge began 4 hours
      (peak plasma concentration) after a single dose of placebo or 5, 20, 100, and 250
      mg montelukast. In trial B, and LTD4 challenge was started 20 hours after
      administration of placebo, 40 mg montelukast, or 200 mg montelukast. During each
      challenge, twofold increasing concentrations of LTD4 were inhaled until specific
      airways conductance (sGaw) decreased by at least 50% (PC50) or the highest
      concentration of LTD4 was inhaled. In trial A with all doses and in trial B with
      the 200 mg dose, bronchoconstriction was attenuated (50% fall in sGaw was not
      observed) up to the highest dose of LTD4 administered. In trial B, during the 40
      mg period, only two of six patients exhibited a 50% fall in sGaw; PC50 ratios
      (montelukast 40 mg/placebo) were 18 and 45 in these two patients. These results
      indicate that montelukast is a highly potent and long-lasting antagonist of LTD4
      induced bronchoconstriction in patients with asthma.

PMID- 9024177
TI  - Temporal decline in filling prescriptions for terfenadine closely in time with
      those for either ketoconazole or erythromycin.
AB  - Temporal changes in the rates of filling terfenadine prescriptions within 2 days
      of those for either oral erythromycin or oral ketoconazole were described with
      use of paid pharmacy claims data from 1988 through 1994 in state Medicaid
      programs from Michigan and Ohio and in a large health maintenance organization.
      There were rapid and significant declines in the rates of filling prescriptions
      for either erythromycin or ketoconazole within 2 days of prescriptions for
      terfenadine in all three databases that coincided with 1992 publicity about the
      cardiovascular risk of terfenadine. These findings suggest that the use of
      terfenadine with contraindicated medications has declined in response to
      relabeling and publicity concerning the safe use of terfenadine. Further study is
      necessary to estimate the absolute level of concurrent use of terfenadine with
      contraindicated medications.

PMID- 9024178
TI  - Pneumonia in the surgical patient.

PMID- 9024179
TI  - Human epileptogenesis and hypothalamic hamartomas: new lessons from an experiment
      of nature.

PMID- 9024180
TI  - The idiopathic generalized epilepsies of adolescence with childhood and juvenile
      age of onset.

PMID- 9024181
TI  - Epilepsy in the developing brain: lessons from the laboratory and clinic.
AB  - Children with epilepsy present unique challenges to the clinician. In addition to
      having differences in clinical and EEG phenomena, children differ from adults in
      regard to etiological factors, response to antiepileptic drugs (AEDs), and
      outcome. It is now recognized that the immature brain also differs from the
      mature brain in the basic mechanisms of epileptogenesis and propagation of
      seizures. The immature brain is more prone to seizures due to an imbalance
      between excitation and inhibition. gamma-Aminobutyric acid (GABA), the major CNS
      inhibitory neurotransmitter in the mature brain, can lead to depolarization in
      the hippocampal CA3 region in very young rats. There are also age-related
      differences in response to GABA agonists and antagonists in the substantia nigra,
      a structure important in the propagation of seizures. These age-related
      differences in response to GABAergic agents provide further evidence that the
      pathophysiology of seizures in the immature brain differs from that in the mature
      brain. Although prolonged seizures can cause brain damage at any age, the extent
      of brain damage after prolonged seizures is highly age dependent. Far less
      histological damage and fewer disturbances in cognition result from prolonged
      seizures in the immature brain than from seizures of similar duration and
      intensity in mature animals. However, detrimental effects of AEDs may be greater
      in the immature brain, than in the mature brain. These lessons from the animal
      laboratory raise questions about the appropriateness of current therapeutic
      approaches to childhood seizure disorders.

PMID- 9024182
TI  - Prognosis of epilepsy: a review and further analysis of the first nine years of
      the British National General Practice Study of Epilepsy, a prospective population
      based study.
AB  - PURPOSE: To understand the prognosis of newly diagnosed epilepsy to provide
      rational therapy and advice for patients and their physicians. METHODS: The
      National General Practice Study of Epilepsy (NGPSE) is the first large population
      based study that has assessed the prognosis of patients with newly diagnosed
      epilepsy prospectively over a prolonged period. We review the previously
      published data on the prognosis of epilepsy after 9 years of follow-up. One
      thousand ninety-one patients with newly diagnosed or suspected epilepsy who were
      attending 1 of 275 general practices throughout the United Kingdom between 1984
      and 1987 were ascertained. Cases in this study were defined as the occurrence of
      one or more seizures, including provoked seizures. Prognosis in terms of
      remission of seizures, and mortality, was analyzed in the patients who were
      classified 6 months after recruitment as having definite epilepsy (n = 564) or
      possible/probable epilepsy (n = 228). RESULTS: Only 33 patients were completely
      lost to follow-up. After 9 years, 86% [95% confidence interval (CI) 81, 90] of
      patients with definite epilepsy had achieved a remission of 3 years, and 68% (CI
      61, 75), had achieved a remission of 5 years. For the complete cohort, with
      possible/probable epilepsy included, the rates increased to 87% (CI 83, 91) for 3
      year remission and 71% (CI 65, 77) for 5-year remission. The proportion of
      patients with definite epilepsy who were still in remission at 9-year follow-up
      (terminal remission) was 68% (CI 62, 74) for 3-year remission and 54% (CI 48, 60)
      for 5-year remission. When stratified by etiology, the proportions achieving 5
      year remission by 9 years was 69% (CI 60, 77) for idiopathic seizures, and 61%
      (CI 46, 75) for remote symptomatic epilepsy. Age and seizure type had small
      effects on the chances of achieving remission, with children experiencing
      slightly lower rates than older patients, and partial seizures having lower
      remission rates than generalized seizures. The overall standardized mortality
      ratio (SMR) for patients with definite or possible/probable epilepsy was 2.5 (CI
      2.1, 2.9), and 3.0 (CI 2.5, 3.7) for patients who were classified as having
      definite epilepsy. The SMR for patients with idiopathic epilepsy was 1.6 (CI 1.0,
      2.4), for those with remote symptomatic epilepsy it was 4.3 (CI 3.3, 5.5), and
      for those with acute symptomatic epilepsy it was 2.9 (CI 1.7, 4.5). CONCLUSIONS:
      Overall, most patients with epilepsy will enter remission; however, there is a
      higher than expected risk of death, especially in those with symptomatic
      epilepsy.

PMID- 9024183
TI  - Sudden unexplained death in epilepsy: observations from a large clinical
      development program.
AB  - PURPOSE: The present study was conducted to determine the rate of sudden
      unexplained death in epilepsy (SUDEP) in a well-defined cohort of patients
      included in the lamotrigine (LTG) clinical development database. METHODS: A panel
      of scientists experienced in the area of SUDEP was assembled and provided with
      case summaries on all deaths (n = 45) reported during the initial clinical
      development of LTG. The panel developed a set of criteria for classifying cases
      as SUDEP (definite or highly probable), possible SUDEP, or non-SUDEP. This
      classification algorithm was then applied to the LTG cases, and SUDEP rates were
      calculated using patient-years of exposure as the denominator. RESULTS: At the
      time of the study, 4,700 patients (5,747 patient-years of exposure) were included
      in the worldwide LTG clinical trials database. In this cohort, 45 deaths were
      reported. Eighteen were judged by the panel to be SUDEP, 6 were defined as
      possible SUDEP, 20 were judged to be due to other causes (non-SUDEP), and 1
      lacked sufficient data from which to make a classification. The overall SUDEP
      rate (definite/ highly probable SUDEP and possible SUDEP combined) was calculated
      to be 3.5 in 1,000 patient-years of exposure to LTG. CONCLUSIONS: The rate of
      SUDEP in this cohort of patients was comparable to the rate that would be
      expected in young adults with severe epilepsy (the subgroup of patients believed
      to be at highest risk of SUDEP). The data suggest that the rate of SUDEP in the
      LTG clinical development program is a function of the clinical trial population
      and is unrelated to drug treatment.

PMID- 9024184
TI  - Effects of sleep and sleep stage on epileptic and nonepileptic seizures.
AB  - PURPOSE: Previous studies of patients with epilepsy and animal models of epilepsy
      suggest that sleep increases the frequency, duration, and secondary
      generalization of seizures. This information is, however, incomplete. METHODS: We
      retrospectively examined video-EEG monitoring reports from our comprehensive
      epilepsy center. We recorded seizure type, site of onset (for partial seizures),
      sleep state at onset, and whether partial seizures secondarily generalized.
      Seizures arising from sleep were then reviewed to determine sleep state. RESULTS:
      We analyzed 1,116 seizures in 188 patients. Thirty-five percent of complex
      partial seizures (CPSs) starting during sleep underwent secondary generalization
      compared with 18% in wakefulness (p < 0.0001). Frontal lobe CPSs secondarily
      generalized at equal rates during sleep (22%) and wakefulness (20%), but temporal
      lobe CPSs generalized much more frequently during sleep (45%) than in wakefulness
      (19%; p < 0.0001). Frontal lobe seizures were more likely to occur during sleep
      (37%) than were temporal lobe seizures (26%; p = 0.0068). CPSs were more frequent
      in stages 1 and 2 and occurred rarely during REM. Seizures starting during slow
      wave sleep were significantly longer than seizures starting during wakefulness or
      stage 2 sleep. Psychogenic nonepileptic seizures (PNESs) were rare between
      midnight and 6 a m. and never occurred during sleep. CONCLUSIONS: Sleep has a
      pronounced effect on secondary generalization of partial seizures, especially
      those of temporal lobe origin. Frontal lobe seizures occur more often during
      sleep than do temporal lobe seizures, and occurrence during sleep helps to
      distinguish PNESs from CPSs.

PMID- 9024185
TI  - Colonic absorption of antiepileptic agents.
AB  - PURPOSE: To evaluate a canine intestinal accessport model to study colonic
      absorption of drugs. The antiepileptic drugs phenytoin and gabapentin were chosen
      to study absorption of a lipophilic and hydrophilic compound, respectively.
      METHODS: Drug plasma level-time plots were generated subsequent to small
      intestinal and colonic drug administration of both drugs. The poorly water
      soluble phenytoin was administered in two doses to evaluate the impact of
      dissolution rate limits on colonic absorption. Maximal plasma concentration
      (Cmax) and area under the plasma level-time curve (AUC) were used to assess the
      relative contribution of colonic absorption to plasma levels. RESULTS: Whereas
      colonic gabapentin AUC and Cmax were only 0.25 and 0.15 of those seen after small
      intestinal administration, colonic phenytoin AUC and Cmax were one half and
      equivalent to, respectively, those observed for small intestinal administration.
      Furthermore, colonic administration of a higher phenytoin dose showed secondary
      maxima and continued increases in drug plasma levels with time. CONCLUSIONS:
      Colonic gabapentin absorption is poor compared with upper intestinal absorption,
      consistent with membrane transport rate limits to the absorption of this
      hydrophilic AED. Peak phenytoin plasma levels from colonic and small intestinal
      administration are comparable, indicating membrane transport does not limit
      absorption of this lipophilic agent. Continued plasma-level increases from higher
      phenytoin doses are consistent with dissolution-rate control of drug absorption
      in the colon. We suggest that colonic absorption provides a greater potential for
      toxicity from phenytoin overdose as a function of continued drug dissolution than
      for gabapentin overdose.

PMID- 9024186
TI  - Lamotrigine adjunctive therapy in childhood epileptic encephalopathy (the Lennox
      Gastaut syndrome).
AB  - PURPOSE: We assessed efficacy and safety of adjunctive lamotrigine (LTG) therapy
      in patients with the Lennox-Gastaut syndrome (LGS). METHODS: The study was a
      single-center, retrospective chart review of open-label adjunctive LTG therapy in
      patients with LGS. Initial LTG dose and titration was dependent on concomitant
      antiepileptic drugs (AEDs). Efficacy was based on the change in seizure frequency
      between the initiation of LTG therapy and December 1, 1995 (or LTG
      discontinuation). Seizure diaries were used to count patient seizures. A
      secondary evaluation of efficacy was a parental or guardian assessment of the
      patient's global status. The evaluation of safety involved chart review for
      treatment-emergent adverse events (AE). RESULTS: Data from 16 LGS patients were
      analyzed. Fifty-three percent (8 of 15) had a > 50% reduction in seizure
      frequency with LTG adjunctive therapy. Tonic, atonic, generalized tonic-clonic
      (GTCS), and atypical absence seizure frequency but not myoclonic seizure
      frequency decreased significantly during LTG therapy. Fifty-three percent of the
      patient's parents (8 of 15) reported that their child's quality of life (QOL) was
      much or very much improved during the study. The major treatment-emergent AE were
      infection (50%, 8 of 16) and sleep disturbance (19%, 3 of 16). A rash was noted
      in 13% (2 of 16) of the patients and resulted in LTG discontinuation in 1. No
      clinically significant changes were noted in neurologic examination or laboratory
      tests during the study. CONCLUSIONS: Our results indicate that LTG adjunctive
      therapy is effective and well tolerated in patients with LGS.

PMID- 9024187
TI  - Hippocampal atrophy is not a major determinant of regional hypometabolism in
      temporal lobe epilepsy.
AB  - PURPOSE: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron
      emission tomography (FDG-PET) temporal lobe hypometabolism in patients with
      hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that
      hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is
      largely responsible for the regional hypometabolism in HS. METHODS: Regions of
      interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and
      posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry
      index for each ROI was calculated. These results were correlated with hippocampal
      magnetic resonance imaging (MRI) volume ratios. RESULTS: There was no correlation
      between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio
      for the mesial or lateral temporal regions (r = -0.09, r = -0.04). When the
      right/left asymmetry index was compared with the right/left hippocampal volume
      ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and
      lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply
      indicated that both tests accurately reflect the side of the epileptogenic
      region. The concordance of the side of relative hypometabolism of the FDG-PET
      with the side of the hippocampal atrophy was higher for the mesial temporal
      region (100%) than for the lateral (77.5%). CONCLUSIONS: The lack of correlation
      between the magnitudes of the ratios argues against hippocampal atrophy and cell
      loss having a central role in the FDG-PET temporal hypometabolism.

PMID- 9024188
TI  - FDG-positron emission tomography and invasive EEG: seizure focus detection and
      surgical outcome.
AB  - PURPOSE: To study the value of [18F]2-deoxyglucose (FDG)-positron emission
      tomography when surface ictal EEG is nonlocalizing. METHODS: FDG-PET scans were
      performed in 46 patients with complex partial seizures (CPS) not localized by
      ictal surface-sphenoidal video-EEG (VEEG) telemetry. Interictal PET was performed
      with continuous EEG monitoring, and images were analyzed with a standard
      template. Forty patients subsequently had subdural and 6 had depth electrodes
      (invasive EEG, IEEG); 22 had bilateral implants. A focus was detected in 40, and
      35 had temporal lobectomy based on IEEG localization. RESULTS: There was a close
      association between IEEG and PET localization (p < 0.01): 26 patients had
      relative unilateral temporal FDG-PET hypometabolism, all had congruent IEEG, and
      18 of 23 were seizure-free after temporal lobectomy. Five patients had unilateral
      frontotemporal hypometabolism (3 of 5 were seizure-free), 1 had frontal
      hypometabolism, and 14 had no lateralized PET abnormality (4 of 7 were seizure
      free). Patients who became seizure-free had significantly higher lateral temporal
      asymmetry index (AI). PET showed > or = 15% relative temporal hypometabolism (AI)
      in 12 of 22 patients with nonlateralized surface ictal VEEG and was capable of
      distinguishing between frontal and temporal foci in 16 of 24 patients with
      lateralized, but not localized, surface ictal video-EEG. CONCLUSIONS: FDG-PET
      provides valuable data in patients with unlocalized surface ictal EEG and can
      reduce the number of patients who require IEEG studies. Quantitation is necessary
      for optimal PET interpretation.

PMID- 9024190
TI  - Functional anatomy of spontaneous seizures in a rat model of limbic epilepsy.
AB  - PURPOSE: The substrate of seizure initiation in partial epilepsy is not well
      understood. Although many studies imply a focus that is will localized to a
      single structure, some information suggests that seizures arise regionally with
      simultaneous or near-simultaneous onset at several separate sites. To determine
      the physiological pattern of seizure onset, recordings were made of spontaneous
      seizures from multiple limbic structures in a rat model of limbic epilepsy.
      METHODS: Seventeen rats with chronic spontaneous limbic seizures that occurred
      after an episode of electrical hippocampal stimulation-induced status epilepticus
      (SE) underwent chronic recording of seizures with a minimum of four electrodes
      placed bilaterally in the midventral hippocampus and either the amygdala or
      piriform cortex. As many as 15 of the first recorded spontaneous seizures (mean
      of 12 seizures, range 2-15) was evaluated for each animal with regard to pattern
      of seizure onset (focal hippocampal, focal nonhippocampal, or diffuse). The
      results were evaluated for number of seizure patterns displayed by each animal
      and the potential change in the pattern of onset with successive seizures (from
      the first to the fifteenth). RESULTS: In all, 210 seizures were evaluated
      beginning 1 week after SE and with monitoring lasting < or = 18 weeks (mean
      recording duration 6 weeks) to record a maximum of 15 seizures for each animal.
      Overall, 54% of the seizures were of diffuse onset, 25% were of nonhippocampal
      onset, and 21% were of hippocampal onset. Eight of the 17 (47%) animals had
      seizures with all three patterns of onset. Evaluation of the evolution of the
      pattern of onset from the first to the fifteenth seizure recorded for the animals
      showed a clear tendency for the later seizures to have diffuse onsets (regression
      analysis r = 0.737, p < 0.002). Qualitative histologic analysis demonstrated
      neuronal loss in the recorded regions. CONCLUSIONS: These findings indicate that
      the epileptogenic zone is broad in this model of limbic "focal" epilepsy and
      suggest that the substrate for seizure generation is distributed over several
      structures.

PMID- 9024189
TI  - Temporal changes in proton MRS metabolites after kainic acid-induced seizures in
      rat brain.
AB  - PURPOSE: In situ 1H-magnetic resonance spectroscopy (MRS) was used to study
      temporal metabolic changes in a rat model of temporal lobe epilepsy (TLE) by
      using kainic acid (KA). METHODS: Rat brains were scanned at the level of the
      hippocampal body for MRS measurements. Relative ratios of N-acetyl groups (NA: N
      acetylaspartate and N-acetylaspartyl glutamate), choline, and lactate (Lac) over
      creatine (Cr) were calculated. RESULTS: NA/Cr ratios increased significantly
      during the ictal phase. During the postictal and interictal phases, the NA/Cr
      ratio decreased. There was a significant and prolonged increase of the lactate/Cr
      ratio in the hippocampi of rats that started 1 h after the onset of KA-induced
      seizure activity and persisted up to 24 h after the injection. The prolonged
      lactate/Cr increase in an area susceptible to neuronal damage (e.g., hippocampus)
      correlated with the onset of seizure activity but remained elevated thereafter.
      CONCLUSIONS: The ictal and early postictal increase in lactate ratios may reflect
      increased cellular activity and metabolism resulting from KA excitotoxicity.
      Assuming that the changes in NA/Cr ratios are due to NAA increase, we speculate
      that an activation of the N-acetylaspartylglutamate (NAAG) dipeptidase pathway
      may explain the ictal increase in NA/Cr ratios. The late postictal decrease in
      NA/Cr ratios is a reflection of KA-induced neuronal cell loss.

PMID- 9024191
TI  - Intravenous carbamazepine: comparison of different parenteral formulations in a
      mouse model of convulsive status epilepticus.
AB  - PURPOSE: A drawback of carbamazepine (CBZ), a major antiepileptic drug (AED) with
      clinical efficacy against partial and generalized convulsive seizures, is its
      isolubility in aqueous vehicles, which is generally considered a contraindication
      to parenteral administration in epileptic patients. However, CBZ can be dissolved
      in glycofurol, a solvent used clinically as a vehicle for parenteral preparations
      of drugs such as diazepam (DZP) and phenytoin (PHT). Furthermore, aqueous CBZ
      solutions can be prepared by complexing CBZ with 2-hydroxypropyl-beta
      cyclodextrin (HP beta CD), an inert beta-cyclodextrin derivative believed to have
      acceptable tolerability for human use. Such solutions of CBZ have been proposed
      to be suitable for intravenous administration in treatment of convulsive (grand
      mal) status epilepticus (CSE). METHODS: A series of five generalized tonic-clonic
      seizures (GTCS) in 30 min was induced by repeated transauricular electrical
      stimulation in mice. In this model of convulsive (grand mal) SE, the
      anticonvulsant potency of intravenous CBZ dissolved in aqueous dilutions of
      either HP beta CD or glycofurol was evaluated. RESULTS: In both solutions, CBZ
      rapidly suppressed seizures after intravenous bolus injection. Potent
      anticonvulsant activity was obtained as early as 30 s after injection, and peak
      effects were observed at approximately 3 min. ED50 for blockade of GTCS
      throughout the 30-min period of repeated electrical stimulation was approximately
      7 mg/kg, similar to the potency of DZP in this model. Whereas the HP beta CD/CBZ
      solutions were tolerated by the animals, with no pronounced behavioral or motor
      adverse effects, the glycofurol/CBZ solutions induced marked sedation and motor
      impairment, indicating interactions between drug and solvent. Determination of
      CBZ in plasma and brain demonstrated that the rapid onset of anticonvulsant
      action after intravenous bolus injection was related to rapid drug penetration
      into brain tissue. CONCLUSIONS: An intravenous formulation of CBZ achieved
      through complexing with HP beta CD might be suitable for parenteral use in acute
      clinical conditions such as SE, particularly because CBZ has the advantage of
      being almost free of respiratory or cardiovascular adverse effects.

PMID- 9024192
TI  - Ictal laughter associated with paroxysmal hypothalamopituitary dysfunction.
AB  - PURPOSE: Seizures with ictal laughter (also termed gelastic seizures) have been
      associated with hypothalamic hamartomas and precocious puberty. It is not known,
      however, where in the brain such seizures originate. We describe a child with
      gelastic seizures and a hypothalamic lesion (probably a hamartoma) in whom two
      dysfunctional phenomena were observed. RESULTS: First, there was a hyperperfusion
      in the hypothalamopituitary areas shown by ictal [99m]Tc hexamethyl
      propyleneamine oxime (HM-PAO) single photon-emission computed tomography (SPECT).
      Second, there was an ictal pulse of gonadotropins, 17 beta-estradiol, and growth
      hormone well above the normal limits in one of the seizures. CONCLUSION: These
      findings suggest that gelastic seizures associated with hypothalamic hamartomas
      are generated in the hypothalamus or in its neighboring regions and that these
      seizures may cause paroxysmal dysfunction of the hypothalamopituitary axis.

PMID- 9024193
TI  - Complex partial seizure provocation by vasovagal syncope: video-EEG and
      intracranial electrode documentation.
AB  - Vasovagal syncope precipitating an epileptic seizure has only rarely been
      described. A patient with known intractable complex partial seizures being
      evaluated for a left anterior temporal lobectomy experienced a typical seizure
      with mesial temporal onset precipitated by an observed vasovagal episode. This is
      the first report of a partial epileptic seizure precipitated by vasovagal syncope
      and the first example of an epileptic seizure induced by syncope in an adult.
      Video and intracranial depth electrode and subdural grid recordings documented
      the event.

PMID- 9024194
TI  - False lateralization of seizure perceived by a patient with infarction of the
      right parietal lobe who showed the neglect syndrome.
AB  - A 66-year-old right-handed man developed seizures characterized by an electric
      sensation and convulsive movements involving the left arm, which sometimes
      secondarily generalized. The patient, however, reported that the seizures
      occurred in his right arm. Neurological examination showed many features of left
      hemineglect, including allesthesia, secondary to acute infarction of the right
      parietal lobe. Although allesthetic response was not documented during the
      seizure, it is likely that sensory symptoms of the seizures were localized
      inappropriately or that he had false memory for lateralization of seizures. In
      this case, the neglect syndrome caused by infarction of the right parietal lobe
      extended to symptoms of the seizure itself.

PMID- 9024195
TI  - The American Epilepsy Society: an historic perspective on 50 years of advances in
      research.

PMID- 9024196
TI  - Schistosoma mansoni: distribution patterns of miracidia among Biomphalaria
      glabrata snail as related to host susceptibility and sporocyst regulatory
      processes.
AB  - Parasite prevalences, miracidia developmental capacity, mother sporocyst mean
      intensities, sporocyst distribution patterns, and cercarial production levels
      were determined after individual exposure of Biomphalaria glabrata snails to
      increased doses of Schistosoma mansoni miracidia for two geographical strains
      (Brazilian, BRE, and Guadeloupean, GUA) of host and parasite. For a high level
      (100%) of host-parasite susceptibility and in the absence of mother sporocyst
      regulatory processes for the BRE combination, parasites were randomly dispersed
      among snail hosts with a frequency distribution conforming to a positive
      binomial. In contrast, for a moderate level (65%) of host-parasite susceptibility
      and in the presence of mother sporocyst regulatory processes for the GUA
      combination, parasites were overdispersed among snail hosts with a frequency
      distribution conforming to the negative binomial. Levels of cercarial production
      were found to be strain dependent, to be determined during early development of
      mother sporocysts, and to be correlated with the number of developed mother
      sporocysts. Results were analyzed in the general context of the infrapopulation
      dynamics of the intramolluscan stages of trematode and are discussed in terms of
      their consequences on the distribution of the genetic diversity of adult
      schistosomes among the definitive host population.

PMID- 9024197
TI  - Strongyloides venezuelensis: adhesion of adult worms to culture vessels by orally
      secreted mucosubstances.
AB  - Adults worms of Strongyloides venezuelensis were cultured in vitro. After
      overnight incubation, about 60% of the worms adhered firmly to the bottom of
      culture vessels by secreting adhesive substances from the mouth. A single worm
      produced 24.5 +/- 10.1 of the adhesion spots overnight. When they were
      transferred to new culture vessels, they still produced new spots comparable to
      those produced for first 24 hr. The adhesion spots were positively stained with
      Coomassie brilliant blue and also with mucicarmine, periodic acid-Schiff, and
      alcian blue, pH 2.5, but not with alcian blue, pH 0.3, indicating their
      glycoprotein nature. The substances were amorphous and did not contain cells or
      nuclei. Histologic staining with a panel of lectins showed that the adhesive
      substances were rich in mannose, N-acetyl galactosamine, and N-acetyl
      glucosamine, but devoid of sialic acid. These characteristics were distinct from
      those of jejunal goblet cell mucins of rats. Adhesive substances contained
      antigenic components recognized by sera from infected rats. Thus, the adhesive
      substances secreted from the mouth of S. venezuelensis were clearly of parasite
      origin. We consider the production/secretion of the adhesive substances by S.
      venezuelensis adult worms a key step for the parasites to invade and establish
      the host epithelial layer.

PMID- 9024198
TI  - Trypanosoma brucei: identification of an internal region of phosphoglycerate
      kinase required for targeting to glycosomal microbodies.
AB  - Among the microbodies found in eukaryotes are the glycosomes of Trypanosoma
      brucei, thought to be closely related to peroxisomes. Two types of targeting
      signals for glycosomes have been identified thus far: type 1 at the C-terminus
      and type 2 at the N-terminus. In this report, we use an epitope-tagging system to
      characterize the targeting signal found on the minor glycosomal isozyme of
      phosphoglycerate kinase, 56PGK. No type 1 or 2 signal was found; rather, the
      topogenic information was found to be internal. Chimeric molecules formed with
      the cytoplasmic phosphoglycerate kinase isozyme indicate that a region between
      amino acids 24 and 91 of 56PGK is essential for glycosomal targeting. No homology
      was found between this region and peroxisomal proteins containing internal
      targeting signals.

PMID- 9024199
TI  - Neospora caninum: role for immune cytokines in host immunity.
AB  - Neospora caninum is a coccidial protozoan parasite that infects a large range of
      mammals including dogs, cats, mice, and cattle. Morphologically, N. caninum
      appears indistinguishable from Toxoplasma gondii, although they are genetically
      distinct. To date there have been no reported cases of this infection in humans,
      although nonhuman primates may be susceptible to infection. Inbred A/J mice
      develop no clinical and little histologic evidence of infection in spite of a
      high-dose inoculum of N. caninum. Splenocytes obtained from infected mice
      proliferate in vitro in response to both N. caninum and T. gondii-soluble
      antigen. A transient state of T cell hyporesponsiveness to parasite antigen and
      mitogen was observed at Day 7 p.i. This downregulatory response could be
      partially reversed by the addition of the nitric oxide antagonist LNMMA, but not
      antibody to IL-10. Mice infected with N. caninum produce significant quantities
      of IL-12 and IFN gamma, most evident shortly after infection. In vivo, antibody
      to IL-12 is able to neutralize immune resistance to the parasite. Moreover, in
      vivo depletion of IFN gamma with antibody renders the mice susceptible to
      infection. These observations suggest that N. caninum induces a T cell immune
      response in the infected host that is at least partially mediated by IL-12 and
      IFN gamma.

PMID- 9024200
TI  - Selective killing of Leishmania amastigotes expressing a thymidine kinase suicide
      gene.
AB  - The thymidine kinase gene of Herpes simplex type-1 virus was transfected into
      several Leishmania species to create drug-sensitive mutants. Expression of the
      thymidine kinase gene is not by itself harmful to Leishmania cells but it is
      capable of phosphorylating ganciclovir, a nucleoside analog, into a highly toxic
      product. In addition to the generation of Leishmania promastigotes highly
      sensitive to ganciclovir, the thymidine kinase gene was expressed similarly by
      amastigotes engulfed either by murine or by human macrophages. Leishmania major
      amastigotes expressing thymidine kinase were eliminated by 85% when treated with
      ganciclovir. Selective killing of parasites expressing suicide genes at their
      infective stage could suggest novel strategies for controlling parasitic
      infections.

PMID- 9024201
TI  - Plasmodium chabaudi: immunogenicity of a highly antigenic glutamate-rich protein.
AB  - The immunogenicity of a 93-kDa Plasmodium chabaudi protein that contains
      glutamate-rich tandem repeats was investigated in this study. Immunoblotting with
      various monoclonal antibodies indicates that this 93-kDa protein is equivalent to
      a potential P. chabaudi RESA analogue. However, the sequence of the P. chabaudi
      protein does not exhibit any significant homology to Pf155/RESA. Antibodies
      against the 93-kDa protein appear early during P. chabaudi infection and reach
      high titers. The highest antibody titers are found when the parasitemia is
      descending, suggesting that this protein may play some role in immunity.
      Immunization of mice with the recombinant protein also results in high antibody
      titers, indicating that the protein is quite immunogenic. However, mice immunized
      with recombinant protein and challenged with P. chabaudi do not exhibit a delayed
      appearance of parasitemia, a reduced parasitemia, or a shortened duration of
      parasitemia. Glutamate-rich P. falciparum proteins such as Pf155/RESA, are being
      considered as vaccine candidates. The studies with P. chabaudi suggest that
      interpretation of serological data using glutamate-rich proteins should proceed
      with caution. The glutamate-rich repeats, although highly immunogenic, may not be
      important in host immunity against malaria. However, antibodies that appear late
      in the P. chabaudi infection do appear to play a role in anti-malarial immunity.

PMID- 9024202
TI  - Trichuris suis: thiol protease activity from adult worms.
AB  - Trichuris suis, the whipworm of swine, causes anemia, weight loss, anorexia,
      mucohemorrhagic diarrhea, and death in heavy infections. A zinc metalloprotease
      has been suggested to play a role in the severe enteric pathology associated with
      infection and the infiltration of opportunistic bacteria into deeper tissues in
      the swine colon. In this study, a thiol protease from gut extracts of adult T.
      suis and from excretory/secretory components (E/S) of adult worms was
      characterized using fluorogenic peptide substrates and protein substrate gels.
      The protease cleaved the fluorogenic substrate Z-Phe-Arg-AMC, and this cleavage
      was completely inhibited by the thiol protease inhibitors E-64, leupeptin, Z-Phe
      Ala-CH2F, and Z-Phe-Arg-CH2F. Gelatin substrate gels and fluorescence assays
      using both the gut and the stichosome extracts and E/S revealed enhanced activity
      when 2 mM dithiothreitol or 5 mM cysteine was included in the incubation buffer,
      and optimal activity was seen over a pH range of 5.5 to 8.5. Incubation of gut
      extracts or E/S material with inhibitors of aspartic, serine, or metalloproteases
      had no effect on the cleavage of Z-Phe-Arg-AMC. Thiol protease activity was found
      in extracts of gut tissue but not in the extracts of stichocytes of adult worms.
      N-terminal amino acid sequencing of the protease revealed sequence homologies
      with cathepsin B-like thiol protease identified from parasitic and free-living
      nematodes.

PMID- 9024203
TI  - Leishmania major: comparison of the cathepsin L- and B-like cysteine protease
      genes with those of other trypanosomatids.
AB  - Cysteine proteases play important roles in the pathogenesis of several parasitic
      infections and have been proposed as targets for the structure-based strategy of
      drug design. As a first step toward applying this strategy to design inhibitors
      as antiparasitic agents for leishmaniasis, we have isolated and sequenced the
      full-length clones of two cysteine protease genes from Leishmania major. One of
      the genes is structurally similar to the cathepsin L-like family and the other is
      similar to the cathepsin B-like family of cysteine proteases. The L. major
      cathepsin L-like sequence has a proregion that shares high sequence similarity
      with other cathepsin L sequences but not cathepsin B sequences and has a
      proline/threonine-rich C-terminal extension. The cathepsin L-like gene occurs in
      multiple copies, whereas there may be only one copy of the cathepsin B-like gene.
      Northern blot analyses show that both genes are expressed in the promastigote and
      amastigote stages, and pulse field gel electrophoresis revealed that the
      cathepsin L- and B-like genes are each found on two nonhomologous chromosomes.
      The L. major L-like amino acid sequence is 75% identical to the L. mexicana
      sequence, 74% identical to the L. pifanoi sequence, 47% identical with the
      Trypanosoma cruzi sequence, 47% identical with the T. congolense sequence, and
      45% identical with the T. brucei sequence. L. major is one of two trypanosomatid
      species for which a cathepsin B-like gene has been identified and sequenced; its
      amino acid sequence is 82% identical to the one from L. mexicana. Tree inference
      based on distance and parsimony methods of kinetoplastid cathepsin L proteins
      yielded independent support for phylogenetic hypotheses inferred from analyses of
      ribosomal RNA genes. Because the cathepsin L locus has a high level of
      phylogenetic signal with respect to trypanosomatid taxa, this locus has great
      potential utility for investigating the evolutionary history of trypanosomatids
      and related organisms.

PMID- 9024204
TI  - Giardia intestinalis: purification and partial amino acid sequence of arginine
      deiminase.

PMID- 9024205
TI  - Plasmodium falciparum: purification of erythrocytes infected with live mature
      forms.

PMID- 9024206
TI  - Isolation, cloning, and expression of fatty-acid binding proteins from Fasciola
      gigantica.

PMID- 9024207
TI  - Plasmodium chabaudi: cDNA of Pc96, a protective antigen associated with the
      erythrocyte membrane of infected erythrocytes.

PMID- 9024208
TI  - Schistosoma mansoni: sexing cercariae by PCR without DNA extraction.

PMID- 9024209
TI  - Toxoplasma gondii: metabolism of intracellular tachyzoites is affected by host
      cell ATP production.

PMID- 9024210
TI  - Cloning of genes and expression and antigenicity analysis of the Leishmania
      infantum KMP-11 protein.

PMID- 9024211
TI  - Clinical review 86: Euthyroid sick syndrome: is it a misnomer?
AB  - Alterations in thyroid function tests are very common in patients with NTI.
      Multiple, complex, and incompletely understood mechanisms are involved in these
      abnormalities. Knowledge of these abnormalities is necessary to avoid errors in
      the diagnosis of thyroid disease. Measurement of serum TSH, free T4, and free T3
      levels by direct equilibrium dialysis/RIA methods probably yield most useful
      (accurate) information in the setting of NTI. Patients with low free T4 by these
      methods and normal or low TSH have secondary hypothyroidism. This may be due to
      NTI per se, drugs administered for treatment of NTI, or associated pituitary or
      hypothalamic disease; the latter consideration may require evaluation of cortisol
      reserve, PRL, and/or gonadotropins. A serum TSH level above 20-25 microU/mL
      probably reflects primary hypothyroidism; accompanying findings of goiter, low
      free T4, and positive antithyroid antibodies help establish the diagnosis. An
      elevated serum concentration of rT3 argues against hypothyroidism. Studies have
      demonstrated no discernible benefit of treatment of NTI patients with T4. Some
      studies have shown a few benefits of treatment with T3 in selected cases, but
      much more needs to be learned. There is no evidence of harm by treatment of NTI
      patients with up to replacement doses of T3. As some NTI patients may indeed be
      hypothyroid, the term ESS should be replaced with NTIS.

PMID- 9024212
TI  - The goitrous patient with an elevated serum calcitonin--what to do?

PMID- 9024213
TI  - Interest of routine measurement of serum calcitonin: study in a large series of
      thyroidectomized patients. The French Medullary Study Group.
AB  - The aim of our study was to assess the ability of routine calcitonin (CT)
      measurement to improve the preoperative diagnosis of medullary thyroid carcinoma
      (MTC) in nodular thyroid diseases. We systematically determined basal CT in 1167
      patients before thyroid surgery and performed a pentagastrin (Pg) CT stimulation
      test in 121 of these patients whose basal CT level was normal. Sixteen MTC
      (1.37%) were found on histopathological examination of surgical specimens: 14 in
      the 34 patients (41.1%) with abnormal basal CT levels and 2 in the 1133 patients
      with normal basal CT levels (0.17%). An abnormal increase in Pg-stimulated CT was
      observed in 7 of the 121 patients tested and was related to microscopic MTC in 2
      cases. Among 1167 thyroidectomized patients with nodular thyroid diseases, the
      prevalence of MTC was 1.37% and reached 41.1% when the basal CT level was
      abnormal (3% of the patients). CT evaluation detected MTC, whereas other
      procedures, such as fine needle aspiration cytology, failed, thus allowing early
      radical surgery. CT measurement should thus become a routine part of the
      diagnostic evaluation of nodular thyroid diseases.

PMID- 9024214
TI  - Familial nonmedullary thyroid carcinoma--the case for genetic susceptibility.

PMID- 9024215
TI  - Two families with an autosomal dominant inheritance pattern for papillary
      carcinoma of the thyroid.
AB  - BACKGROUND: Papillary carcinoma of the thyroid (PTC) is the most prevalent
      malignancy of the thyroid gland. Although the majority of lesions are sporadic
      tumors, an established relationship exists between familial adenomatous polyposis
      (FAP) and PTC. Moreover, some authors postulate the existence of familial PTC as
      a distinct entity. Evidence for this is limited, however, there being few well
      characterized descriptions of pedigrees with high prevalence of PTC. AIMS: The
      objective of the present study was to examine an apparent heritable
      predisposition to PTC occurring in two Tasmanian families in which PTC occurs
      commonly. METHODS: Pedigree charts were constructed for both families and the
      medical records of the members reviewed. RESULTS: In Pedigree I, 7 of 25 members
      had PTC (6 of these had coexisting multinodular goiter (MNG), and 11 others had
      MNG. In Pedigree II, identical male twins and their daughters had PTC.
      CONCLUSIONS: In both families there is evidence of autosomal dominant inheritance
      of PTC. The association of PTC with MNG suggests a possible role for MNG in tumor
      pathogenesis in hereditary PTC. The majority of the patients were diagnosed with
      PTC before commencement of prospective screening, indicating clinically relevant
      disease in the families described.

PMID- 9024216
TI  - Is growth hormone deficiency a viable diagnosis?

PMID- 9024217
TI  - Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients
      after completion of treatment.
AB  - GH state and auxological data after completion of GH therapy are reported in 131
      patients (79 males, 52 females). They were treated from 1980-1994 for partial (n
      = 98) or complete (n = 33) GH deficiency (GHD), either idiopathic (n = 121) or
      organic (n = 10). A single stimulation test (clonidine+betaxolol) was used, and
      only 50 patients (38%) maintained a blunted response (GH peak below 10
      micrograms/L). Although 9 of the 10 patients with organic GHD had an abnormal low
      GH peak, 67% of patients with idiopathic GHD normalized their GH secretion. This
      was particularly true of partial GHD patients (71% vs. 36% of complete GH
      deficient patients). Based on a retest GH peak below 5 micrograms/L, only 23% of
      the patients were considered to be GH deficient and therefore candidates for GH
      treatment during adulthood. We found no significant difference between hormonal
      state at completion of treatment and initial GH deficiency, pubertal state, or
      sex, although we did find a significantly lower GH peak value before and after
      treatment in patients with elevated body mass index. Of the 14 obese children who
      were treated, 50% had an abnormally low serum insulin-like growth factor-I level,
      arguing for true GHD, and only two children remained obese at cessation of
      treatment. Auxological data showed that with a mean duration of treatment of 3.6
      +/- 2.0 yr, patients classified as having complete GHD before treatment had
      significantly greater catch-up growth as expressed in SDS for height than
      patients with partial GHD (0.6 +/- 1.1 vs. 1.1 +/- 0.7 SDS, P < 0.05), and that
      boys grew better than girls (1.4 +/- 0.8 vs. 1.6 +/- 0.6 SDS) for height, P <
      0.01). That catch-up growth was not correlated with the result of GH peak after
      cessation of treatment.

PMID- 9024218
TI  - Surgical versus medical management of multiple endocrine neoplasia (MEN) type I.

PMID- 9024219
TI  - Transcription of the human genes for cytochrome P450scc and P450c17 is regulated
      differently in human adrenal NCI-H295 cells than in mouse adrenal Y1 cells.
AB  - Human NCI-H295 cells, which express all of the genes for the steroidogenic
      enzymes in a hormonally regulated fashion, should be an ideal system in which to
      study the transcriptional regulation of these genes. Using deletional
      promoter/reporter constructions for the human P450scc and P450c17 genes, we
      identified the regions conferring basal and cAMP-induced transcription of these
      two genes in NCI-H295 human adrenal cells. In the P450scc gene, both basal and
      cAMP-induced transcriptional activation elements lie within the first 79 bp
      upstream (-79) from the transcriptional start site. In the P450c17 promoter, both
      basal and cAMP-responsive elements lie within the first upstream 63 bp, and a
      second basal element lies between -184 and -206 bp. The locations of these
      elements are substantially different from the locations of elements that appear
      to be functionally equivalent when these human gene promoters are transfected
      into mouse adrenal Y1, mouse testicular MA-10, or human choriocarcinoma JEG-3
      cells. These data indicate that the transcriptional regulation of these genes in
      their native species and cell type differs substantially from their regulation in
      cells from other species and tissues, and suggests that the results from
      transfection experiments examining genes for steroidogenic enzymes in
      heterologous cells may not reflect events in vivo.

PMID- 9024220
TI  - Mitochondrial gene transfer ribonucleic acid (tRNA)Leu(UUR) 3243 and tRNA(Lys)
      8344 mutations and diabetes mellitus in Korea.
AB  - The high prevalence of diabetic patients with a mutation in the mitochondrial
      gene (the 3243 and 8344 bp mutations) has been identified in Japan. To determine
      the prevalence of diabetic patients with those mutations in Korea, we randomly
      screened selected 503 clinical diabetic patients regardless of their diabetes
      types. We found only 1 patient with the mitochondrial DNA mutation at position
      3243 (percent mutation, 32%), and the mitochondrial DNA mutation at position 8344
      was not found in any of the patients. The affected subject was a 22-yr-old man
      with a history of myoclonic epilepsy and mild sensorineural hearing loss, a 1-yr
      duration of diabetes mellitus, and a low level C peptide response to oral
      glucose. Because of the low frequency of these mutations in the Korean diabetic
      population, we concluded that these particular mutations of mitochondrial DNA may
      not be a common contributor to diabetes mellitus in Korea.

PMID- 9024221
TI  - Evaluation of islet cell antigen (ICA) 512/IA-2 autoantibody radioassays using
      overlapping ICA512/IA-2 constructs.
AB  - Islet cell antigen (ICA) 512 also termed IA-2 is a novel autoantigen of type 1
      diabetes, which has a tyrosine phosphatase-like domain. We have assessed
      autoantibody RIAs using a series of ICA512/IA-2 constructs to produce in vitro
      synthesized 35S-methionine-labeled proteins. Levels of ICA512/IA-2 (256-979,
      truncated aminoterminus) autoantibodies were strongly correlated with those of
      the full-length ICA512/IA-2 (1-979) autoantibodies (r = 0.96, P < 0.0001) and
      ICA512/IA-2 (687-979) autoantibodies (r = 0.98, P < 0.0001). RIAs using these 3
      constructs had increased sensitivity relative to our initially reported ICA512
      autoantibody RIA (amino acids 389-948, truncated carboxy- and aminoterminus).
      Only 2 of 38 sera examined in this study reacted with an aminoterminus ICA512/IA
      2 (1-577) construct. The mean SD score (SD score = (index of unknown sample-mean
      index of controls)/SD of controls) using the ICA512/IA-2 (256-979) construct was
      significantly higher than the SD score obtained with other ICA512/IA-2 constructs
      (P < 0.001). Amongst patients with new-onset diabetes and prediabetic relatives,
      using RIAs for autoantibodies reacting with ICA512/IA-2 (256-979), insulin, and
      glutamic acid decarboxylase 65, 98% expressed one or more of these autoantibodies
      and 78% expressed two or more, whereas no control (n = 208) expressed more than a
      single autoantibody. A combined ICA512/IA-2 (256-979), glutamic acid
      decarboxylase 65 autoantibody RIA with differential autoantigen labeling (35S
      methionine, 3H-leucine) has been developed that uses 96-well plate membrane
      filtration and Top Counter beta counting. Concordance between results of dual and
      single RIAs was greater than 90%. This simple combined autoantibody assay should
      facilitate large-scale autoantibody screening.

PMID- 9024222
TI  - Leptin synthesis is resistant to acute effects of insulin in insulin-dependent
      diabetes mellitus patients.
AB  - Insulin stimulates ob gene expression and increases serum leptin concentrations
      in mice and in noninsulin-dependent diabetes mellitus patients. Obese women have
      higher ob gene messenger ribonucleic acid levels than obese men, suggesting that
      sex hormones are involved in the regulation of leptin synthesis. We studied the
      relationship among leptin, insulin, and testosterone in 15 men with insulin
      dependent diabetes mellitus (IDDM; age, 29 +/- 2 yr; body mass index, 22.7 +/-
      0.5 kg/m2; body fat, 9.5 +/- 1.0%; insulin dose, 44 +/- 4 U/day; hemoglobin A1c,
      8.1 +/- 0.3%; diabetes duration, 12.7 +/- 2.0 yr) and 15 healthy control subjects
      (age, 27 +/- 1 yr; body mass index, 22.6 +/- 0.4 kg/m2; body fat, 9.6 +/- 0.5%)
      in the fasting state. In addition, the effect of a 4-h euglycemic
      hyperinsulinemia (approximately 600 pmol/L) on the plasma leptin concentration
      was determined. The fasting leptin concentration was negatively correlated to
      plasma testosterone (r = -0.55; P < 0.05) in IDDM patients. The fasting plasma
      leptin level rose 25% in healthy subjects (from 1.0 +/- 0.2 to 1.3 +/- 0.3 ng/mL;
      P < 0.05). The leptin levels were higher in IDDM subjects (P < 0.01) and remained
      unchanged (2.7 +/- 0.2 vs. 2.7 +/- 0.2 ng/mL) during hyperinsulinemia. We reached
      the following conclusions. 1) In nonobese IDDM patients, leptin synthesis is
      resistant to the acute effect of insulin. 2) Serum testosterone may contribute to
      the regulation of leptin synthesis in IDDM patients.

PMID- 9024223
TI  - Glucose metabolism in identical twins discordant for obesity. The critical role
      of visceral fat.
AB  - Obesity, especially intraabdominally deposited fatness, is associated with
      reduced insulin sensitivity. However, it is not well established whether this
      association is confounded by genetic factors. We studied 23 monozygous twin pairs
      (14 female, 9 male), 33-59 yr old, who had, on the average, 18 kg intrapair
      difference in body weight. A 75-g oral glucose tolerance test with glucose and
      insulin measurements at 30-min intervals was performed, and fat distribution was
      determined with magnetic resonance imaging. The pairs were divided into two
      groups by the gender-specific median of the abdominal visceral fat area (AVF) in
      the obese co-twins. In the high-AVF pairs, the mean area under curve (AUC) for
      glucose (mmol x min/L) was 758 vs. 968 (P = 0.001), AUC for insulin (mU x min/L)
      was 4320 vs. 8741 (P = 0.001), and insulin sensitivity index (mg x L x L/mmol x
      mU x min) was 71.5 vs. 45.9 (P < 0.001) in the lean and obese co-twins,
      respectively. In the low AVF pairs, the mean AUC for glucose was 669 vs. 706 (not
      significant), AUC for insulin was 3323 vs. 4241 (not significant), and the
      sensitivity index was 85.2 vs. 73.7 (P = 0.04) in the lean and obese co-twins,
      respectively. In subjects who are genetically identical but who are discordant
      for body mass, only those who differ most in visceral fat level are characterized
      by major alterations in insulin sensitivity and glucose tolerance.

PMID- 9024224
TI  - Differential effects of hormone-replacement therapy on endogenous nitric oxide
      (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta
      estradiol valerate and cyproterone acetate or medroxyprogesterone acetate.
AB  - Increased incidence of cardiovascular disease in postmenopausal women (PMW) is
      accompanied by ovarian dysfunction; hormone replacement therapy (HRT) can have
      cardioprotective effects. Because hypertension and atherosclerosis are associated
      with impaired release of endothelium-derived nitric oxide (NO) and increased
      levels of low-density lipoproteins (LDL), we investigated whether HRT augments NO
      release, and whether these increases are accompanied by a decrease in LDL levels
      in PMW. We determined serum nitrite/ nitrate (NO2-/NO3-) and LDL levels at
      baseline (before initiation of HRT) and during the 6th and 12th months of the
      study. The PMW (n = 26) received continuous oral administration of estradiol
      valerate (Progynova, 2 mg daily) for 21 days supplemented with either oral
      cyproterone acetate (CPA; 1 mg; n = 11) or medroxyprogesterone acetate (MPA; 5
      mg; n = 15) on days 12-21 of each treatment cycle. Blood samples in the PMW
      receiving HRT were collected at times while the subjects were taking estradiol
      valerate alone and estradiol valerate plus CPA or MPA. Compared with the samples
      collected at baseline, serum NO2-/NO3- levels increased significantly from 20.1
      +/- 1.58 mumol/L at baseline to 30 +/- 3.7 mumol/L (P < 0.01) in samples
      collected after 12 months of HRT while the PMW were not taking progestins (CPA or
      MPA), and to 25.4 +/- 2 mumol/L (P < 0.05) when all the samples, regardless of
      the treatment with CPA or MPA, were included in the analysis. Moreover, > 30%
      increase in serum NO2-/NO3- levels were observed only in 13 (responders) out of
      26 PMW substituted with estradiol valerate, suggesting that estradiol may improve
      endogenous NO synthesis in a differential fashion. Compared with baseline, no
      significant increases in serum NO2-/NO3- were observed in samples collected while
      the estradiol-treated responders were taking either CPA or MPA. In contrast to
      NO2-/NO3- serum LDL levels were significantly reduced in samples collected after
      12 months of HRT (P < 0.05 vs. baseline). Furthermore, levels of NO2-/NO3 showed
      a significant negative correlation with the levels of LDL (r2 = 0.17; P < 0.05)
      in the responders but not in nonresponders. These results indicate that oral
      administration of estradiol valerate in PMW for HRT increases circulating NO
      levels, an effect that may contribute to the cardioprotective effects of HRT in
      PMW. In addition, our data suggests but does not prove that concomitant
      administration of a progestin may attenuate the beneficial effects of estrogen
      replacement therapy with regard to NO release. Finally, our data provides
      evidence for the existence of responders and nonresponders to postmenopausal
      estrogen treatment with respect to improvement of endogenous NO levels,
      suggesting that a significant number, but not all, of the hormonally substituted
      PMW profit fully from the beneficial properties of a HRT.

PMID- 9024225
TI  - Beta 3-adrenergic receptor-mediated lipolysis and oxygen consumption in brown
      adipocytes from cynomolgus monkeys.
AB  - Primary adipocytes were isolated from axillary brown adipose tissue from adult
      cynomolgus monkeys. That this tissue contained brown adipocytes was verified by
      morphological examination and by demonstrating the presence of uncoupling protein
      messenger ribonucleic acid in the isolated adipocytes. The contributions of beta
      1-, beta 2-, and beta 3-adrenergic receptors (AR) to lipolysis and oxygen
      consumption of isolated brown adipocytes were determined after agonist
      stimulation. Dose responses were determined using isoproterenol (a nonselective
      beta-AR agonist), denopamine (beta 1-AR agonist), procaterol (beta 2-AR agonist),
      and CGP12177A (beta 1- and beta 2-AR antagonist, beta 3-AR agonist).
      Isoproterenol, denopamine, and procaterol stimulated lipolysis with EC50 values
      of 4,500, and 83 nmol/L, respectively. Intrinsic activities (relative to
      isoproterenol maxima) were 100%, 74%, and 59%, respectively. The presence of beta
      3-ARs coupled to lipolysis was demonstrated by the activity of CGP12177A (EC50 =
      1.6 mumol/L; intrinsic activity = 62%). Isoproterenol stimulated oxygen
      consumption of brown adipocytes by 75-100% above the basal rate, with an EC50 of
      1 mumol/L. Denopamine, procaterol, and CGP12177A stimulated oxygen consumption at
      a concentration of 100 mumol/L. These results demonstrate that all three beta
      adrenergic receptor subtypes are coupled to lipolysis and oxygen consumption in
      brown adipocytes from cynomolgus monkeys.

PMID- 9024226
TI  - Insulin resistance in short children with intrauterine growth retardation.
AB  - Epidemiological studies have demonstrated an association between intrauterine
      growth retardation and an increased risk of adult diseases that include essential
      hypertension, noninsulin-dependent diabetes mellitus, and ischemic heart disease.
      A common feature of these diseases is insulin resistance. To investigate whether
      abnormal insulin sensitivity was a characteristic of subjects with intrauterine
      growth retardation (IUGR), we compared two groups of short prepubertal children:
      a group with IUGR (birth weight less than the tenth percentile; n = 15) and a
      normal birth weight group (n = 12). Subjects underwent a modified frequently
      sampled iv glucose tolerance test that permitted calculation of the acute insulin
      response, insulin sensitivity index, and glucose effectiveness. A marked
      difference in the insulin sensitivity index was noted between groups, with the
      IUGR group being less insulin sensitive [6.9 vs. 16.9 10(-4)min-1.(microU/mL); P
      = 0.0048]. The acute insulin response was also significantly different between
      groups, with IUGR subjects having higher insulin levels (445 vs. 174 microU/mL; P
      = 0.005). There was no difference in glucose effectiveness between groups. Short
      prepubertal IUGR children have a specific impairment in insulin sensitivity
      compared to their normal birth weight peers. In short IUGR children, impaired
      insulin sensitivity is a potential marker for the early identification and
      intervention in the development of late adult-onset noninsulin-dependent diabetes
      mellitus.

PMID- 9024227
TI  - Testosterone replacement increases fat-free mass and muscle size in hypogonadal
      men.
AB  - Testosterone-induced nitrogen retention in castrated male animals and sex-related
      differences in the size of the muscles in male and female animals have been cited
      as evidence that testosterone has anabolic effects. However, the effects of
      testosterone on body composition and muscle size have not been rigorously
      studied. The objective of this study was to determine the effects of replacement
      doses of testosterone on fat-free mass and muscle size in healthy hypogonadal men
      in the setting of controlled nutritional intake and exercise level. Seven
      hypogonadal men, 19-47 yr of age, after at least a 12-week washout from previous
      androgen therapy, were treated for 10 weeks with testosterone enanthate (100
      mg/week) by im injections. Body weight, fat-free mass measured by underwater
      weighing and deuterated water dilution, and muscle size measured by magnetic
      resonance imaging were assessed before and after treatment. Energy and protein
      intake were standardized at 35 Cal/kg.day and 1.5 g/kg.day, respectively. Body
      weight increased significantly from 79.2 +/- 5.6 to 83.7 +/- 5.7 kg after 10
      weeks of testosterone replacement therapy (weight gain, 4.5 +/- 0.6 kg; P =
      0.0064). Fat-free mass, measured by underwater weighing, increased from 56.0 +/-
      2.5 to 60.9 +/- 2.2 kg (change, +5.0 +/- 0.7 kg; P = 0.0004), but percent fat did
      not significantly change. Similar increases in fat-free mass were observed with
      the deuterated water method. The cross-sectional area of the triceps arm muscle
      increased from 2421 +/- 317 to 2721 +/- 239 mm2 (P = 0.045), and that of the
      quadriceps leg muscle increased from 7173 +/- 464 to 7720 +/- 454 mm2 (P =
      0.0427), measured by magnetic resonance imaging. Muscle strength, assessed by one
      repetition maximum of weight-lifting exercises increased significantly after
      testosterone treatment. L-[1-13C]Leucine turnover, leucine oxidation, and
      nonoxidative disappearance of leucine did not significantly change after 10 weeks
      of treatment. There was no significant change in hemoglobin, hematocrit,
      creatinine, and transaminase levels. Replacement doses of testosterone increase
      fat-free mass and muscle size and strength in hypogonadal men. Whether androgen
      replacement in wasting states characterized by low testosterone levels will have
      similar anabolic effects remains to be studied.

PMID- 9024228
TI  - Body weight, body fat distribution, and hormonal replacement therapy in early
      postmenopausal women.
AB  - Body weight was measured, and body fat distribution was determined by dual energy
      x-ray in early postmenopausal women given either oral calcium (500 mg/day;
      control group; n = 12) or hormonal replacement therapy (HRT), a combination of
      estradiol valerate (2 mg/day for 21 days) with cyproterone acetate (1 mg/day in
      the last 10 days of the treatment cycle; n = 15). There were no differences in
      basal body weight or body fat distribution in the two groups before the study. In
      the control group, a significant (P < 0.05) increase in body weight (from 63.6 +/
      2.2 to 65.2 +/- 1.9 kg [corrected] after 12 months) paralleled a slight, but
      significant (P < 0.05), increase in total body fat mass (from 23.8 +/- 2.2 to
      24.7 +/- 2.2 kg), with an increase in fat in the trunk (from 10.2 +/- 0.4 to 11.3
      +/- 0.4 kg; P < 0.01) and arms (from 2.4 +/- 0.5 to 2.7 +/- 0.2 kg; P < 0.05).
      These findings demonstrate a shift to a prevalent central android fat
      distribution after 12 months of observation in untreated postmenopausal women.
      Conversely, in the HRT group, total body bone mineral showed a significant (from
      1089 +/- 28 to 1106 +/- 29 mg/cm2; P < 0.05) increase after 12 months, with no
      significant increase in body weight (from 62.2 +/- 1.6 to 62.7 +/- 1.6 kg), and
      no modifications in trunk (from 10.0 +/- 0.2 to 9.8 +/- 0.3 kg) and arm (from
      2.43 +/- 0.2 to 2.5 +/- 0.1 kg) fat, but a significant increase in leg fat (from
      7.1 +/- 0.3 to 8.3 +/- 0.4 kg; P < 0.05). The present results suggest that HRT
      can counteract at least in part the postmenopausal increase in body weight and
      body fat and prevent central body fat distribution after menopause.

PMID- 9024229
TI  - Adult height in growth hormone (GH)-deficient children treated with biosynthetic
      GH. The Genentech Growth Study Group.
AB  - Near-adult height (AH) was determined in 121 children (72 males and 49 females)
      with GH deficiency (GHD) who were prepubertal when they began treatment with
      recombinant DNA-derived preparations of human GH. AH as a SD score was -0.7 +/-
      1.2 (mean +/- SD), significantly greater than the pretreatment height SD score (
      3.1 +/- 1.2), the predicted AH SD score (-2.2 +/- 1.2; Bayley-Pinneau method),
      and the height SD score at the start of puberty (-1.9 +/- 1.3). In contrast to
      studies of GH treatment outcome, which used pituitary-derived GH (pit-GH) in
      lower doses, we found that males did not have a higher AH SD score than females,
      spontaneous puberty did not diminish AH, and AH was significantly greater than
      that predicted at the start of GH treatment. In a multiple regression equation,
      the statistically significant variables (all P < 0.0001) related to AH (r2 =
      0.70) were the following: duration of treatment with GH, sex (males were taller
      than females, as expected for the normal population), age (younger children had a
      greater AH) and height at the start of GH, and growth rate during first year of
      GH. For the AH SD score (r2 = 0.47), pretreatment predicted AH, duration of GH,
      and bone age delay were significant (P < 0.0002) explanatory variables. Bone age
      delay (chronological age-bone age) had a negative impact on the AH SD score.
      Target height, etiology of GHD, previous treatment with pituitary GH, and the
      presence or absence of spontaneous puberty did not significantly improve the
      prediction of AH. Early diagnosis of GHD and continuous treatment with larger
      doses of GH to near AH should improve the outcome in children with short stature
      due to GHD.

PMID- 9024230
TI  - Measurement of human growth hormone receptor messenger ribonucleic acid by a
      quantitative polymerase chain reaction-based assay: demonstration of reduced
      expression after elective surgery.
AB  - Studies of GH receptor (GHR) gene expression in human tissues have been hampered
      by the limited amount of tissue available for analysis and the low sensitivity of
      conventional methods. We have developed a quantitative reverse transcriptase-PCR
      assay for measurement of GHR messenger ribonucleic acid levels in small human
      tissue biopsies. To compensate for sample to sample variation, an internal RNA
      standard, which differs from the wild-type GHR transcript by only a few
      nucleotides, was reverse transcribed and amplified together with the GHR
      transcripts. PCR was carried out using one biotinylated primer to permit the
      purification of single stranded PCR products on streptavidin-coated microtiter
      plates. The ratio between the wild-type and mutated transcripts was determined by
      two separate minisequence reactions in which a primer, annealed immediately 3' of
      a variable nucleotide, was extended by a single 3H-labeled nucleotide,
      complementary to either the wild-type or mutated sequence. The assay range was
      0.125-8 x 10(5) transcripts/sample, the mean intraassay coefficient of variation
      was 8.7%, and the lower limit of detection was 0.125 x 10(5) transcripts/sample.
      GHR messenger ribonucleic acid levels were detectable in small amounts (10-100
      ng) of total RNA extracted from adipose tissue, skeletal muscle, and liver. The
      GHR gene expression in liver was approximately 10-fold higher than that in
      skeletal muscle, whereas intermediate levels were found in adipose tissue. In
      nine patients undergoing elective abdominal surgery, GHR gene expression in
      skeletal muscle was reduced on day 3 after surgery compared to the baseline
      level. The decrease in GHR gene expression was accompanied by a decrease in
      skeletal muscle glutamine. This suggests that the postoperative protein
      catabolism may be caused at least partly by acquired GH insensitivity due to
      reduced expression of the GHR gene.

PMID- 9024231
TI  - Racial differences in bone density between young adult black and white subjects
      persist after adjustment for anthropometric, lifestyle, and biochemical
      differences.
AB  - This study tested whether racial differences in bone density can be explained by
      differences in bone metabolism and lifestyle. A cohort of 402 black and white men
      and women, ages 25-36 yr, was studied at the Kaiser Permanente Medical Care
      Program in Northern California, a prepaid health plan. Body composition (fat,
      lean, and bone mineral density) was measured using a Hologic-2000 dual-energy x
      ray densitometer. Muscle strength, blood and urine chemistry values related to
      calcium metabolism, bone turnover, growth factors, and level of sex and adrenal
      hormones were also measured. Medical history, physical activity, and lifestyle
      were assessed. Statistical analyses using t- and chi-square tests and multiple
      regression were done to determine whether racial difference in bone density
      remained after adjustment for covariates. Bone density at all skeletal sites was
      statistically significantly greater in black than in white subjects; on average,
      adjustment for covariates reduced the percentage density differences by 42% for
      men and 34% for women. Adjusted bone density at various skeletal sites was 4.5
      16.1% higher for black than for white men and was 1.2-7.3% higher for black than
      for white women. We concluded that racial differences in bone mineral density are
      not accounted for by clinical or biochemical variables measured in early
      adulthood.

PMID- 9024232
TI  - Nine novel growth hormone receptor gene mutations in patients with Laron
      syndrome.
AB  - The GH receptor (GHR) is a member of the cytokine receptor superfamily; GH
      binding protein is the solubilized extracellular domain of the GHR. Abnormalities
      in the GHR produce an autosomal recessive form of GH resistance, the Laron
      syndrome, characterized by growth failure and the clinical appearance of severe
      GH deficiency despite elevated circulating GH levels. In 13 unrelated patients
      with undetectable levels of GH binding protein, we characterized nine novel
      mutations in the GHR gene. These molecular defects comprise three nonsense
      mutations (Q65X, W80X, and W157X), one frameshift (36delC), two splice defects (G
      ->A at 70 + 1, C-->T at 723), and three missense mutations (C38S, S40L, and W50R)
      located in the extracellular domain of the receptor, and thus would be expected
      to interfere with GH binding activity. These results further confirm the broad
      heterogeneity of mutations underlying this rare GH resistance syndrome.

PMID- 9024233
TI  - Mild clinical expression of myasthenia gravis associated with autoimmune thyroid
      diseases.
AB  - Myasthenia gravis (MG) may occur in association with autoimmune thyroid diseases
      (AITD). The aim of this study was to evaluate the features of MG associated with
      AITD compared to those of MG without AITD. A total of 129 MG patients (34 men and
      95 women; age range, 11-81 yr) were subdivided into: group A, 56 MG patients with
      AITD [25 with autoimmune thyroiditis and 31 with Graves' disease (GD)]; group B,
      21 MG patients with nonautoimmune thyroid diseases; and group C, 52 MG patients
      without thyroid disease. The severity of MG was ranked according to the Osserman
      score. Laboratory evaluation included assays for antithyroid and
      antiacetylcholine receptor (AchRAb) antibodies. Ocular MG (Osserman's class 1)
      was more frequent in group A (41.0%) than in group B (14.2%; P < 0.03) or C
      (21.4%; P < 0.03). Severe generalized MG (classes > or = 2B) was more frequent in
      groups B (57.1%; P < 0.03) and C (51.9%; P < 0.02) than in group A (28.5%). GD
      patients with clinical evidence of ophthalmopathy had a higher frequency (P =
      0.05) of ocular MG (57.8%) than GD patients without clinical ophthalmopathy
      (16.6%). Thymic disease was less frequent in group A (26.7%) than in group B
      (71.4%; P = 0.001) or C (59.7%; P = 0.001). The prevalence of thymic hyperplasia
      was 17.8%, 38.0%, and 40.3% in groups A, B, and C, respectively; the prevalence
      of thymoma was 8.9%, 33.4%, and 19.4%. When only patients with generalized MG
      were considered, thymic disease was less frequent (P < 0.02) in group A (40.6%)
      than in the remaining groups (69.4%). AchRAb was more frequent in groups B
      (57.1%) and C (57.6%; P < 0.03) than in group A (35.7%). In conclusion, MG
      associated with AITD has a mild clinical expression, with preferential ocular
      involvement and lower frequency of thymic disease and AchRAb. This supports the
      hypothesis that ocular and generalized MG are separate diseases with different
      spectra of associated diseases. Nonautoimmune thyroid diseases have no influence
      on the features of MG. The association of ocular MG and AITD might be due to a
      common autoimmune mechanism and/or a peculiar genetic background.

PMID- 9024234
TI  - Clinical, biochemical, and molecular investigations of a genetic isolate of
      growth hormone insensitivity (Laron's syndrome).
AB  - We have characterized the GH receptor mutation that is responsible for extreme
      short stature and GH insensitivity in a Bahamian genetic isolate. Heights of
      affected individuals ranged from -4.0 to -6.3 SD. Like others with Laron's
      syndrome, they had normal to high serum GH concentrations and low serum insulin
      like growth factor I concentrations. Circulating levels of GH-binding protein
      activity were below limits of detection. Amplification of exons 2-7 and screening
      with single strand conformational polymorphism analysis located an abnormality in
      exon 7. Sequencing identified homozygosity for a C to T transition in the third
      position of codon 236. Reverse transcription and PCR amplification of
      complementary DNA from lymphocytes showed that this same sense mutation generated
      a new splice donor site 63 bp 5' to the normal exon 7 splice site. This novel
      site was used to the exclusion of the normal site in homozygotes. Both normal and
      variant messenger ribonucleic acid species were detected in heterozygotes. The
      predicted protein lacks 21 amino acids, including those defining the WS-like
      motif of the GH receptor extracellular domain. The high frequency of Laron's
      syndrome in this isolated island population probably reflects the introduction of
      the G236 splice mutation by a settler early in the 300-yr history of English
      settlement.

PMID- 9024235
TI  - A 5-year prospective study of growth hormone (GH)-deficient children treated with
      GH before the age of 3 years. French Serono Study Group.
AB  - The aim of the study was to assess the efficacy of GH therapy in GH-deficient
      children treated before the age of 3 yr. A noncomparative multicenter prospective
      study included 49 children (22 girls and 27 boys) with isolated GH deficiency (n
      = 19) or multiple pituitary hormone deficiency (n = 30) treated with daily s.c.
      injections (0.6 U/kg.week) for 3-5 yr. They were divided into two groups
      according to their height SD score for chronological age (CA) at the initiation
      of therapy: group A consisted of 8 patients presenting an initial height within
      the normal range (< 2 SD below the mean) followed for 2-5 yr, and group B
      consisted of 25 children followed for 5 yr among 41 patients with initial growth
      retardation. In group A, the mean height SD score increased from -1.1 +/- 0.6 to
      0.35 +/- 1.0 SD (P < 0.001) in the first year and remained in the normal range
      throughout the following 4 yr. In group B after 4 yr of treatment, the mean
      height SD score for age had increased from -3.6 +/- 1.0 SD (time zero) to -0.9 +/
      1.2 SD. During the fourth year of therapy, the mean height gain of 0.2 +/- 0.2
      SD was significant (P < 0.001). After 5 yr of treatment, a plateau was reached
      with a corresponding height SD score (CA) of -0.8 +/- 1.2 SD (95% confidence
      interval between -1.3 and -0.2 SD). This value remained significantly below
      normal for age (P < 0.001), indicating that catch-up growth was incomplete. Only
      four patients (16%) remained below -2SD for CA. The 5-yr height gain was
      negatively correlated with the height SD score at the start of treatment (r = 
      0.6; P < 0.005) and the first year height gain was the most predictive parameter.
      There was no significant influence of intrauterine growth retardation, body mass
      index and age at the start of treatment, or parental target height. Bone
      maturation was significantly retarded over CA by a mean value of 1.1 +/- 0.9 yr
      (P < 0.0001), with a mean bone age/CA ratio of 0.8 +/- 0.2 after a mean treatment
      duration of 5.1 +/- 1.1 yr. In conclusion, the rapid and almost complete return
      to normal height obtained in this study supports the need for GH treatment in
      early diagnosed GH-deficient children. The present dosage may be considered the
      minimum to obtain satisfactory catch-up growth ensuring a favorable outcome for
      these children. In addition, it allowed growth at a rate normal for age in
      patients diagnosed before growth retardation.

PMID- 9024236
TI  - Effects of nifedipine treatment on the renin-angiotensin-aldosterone axis.
AB  - Nifedipine is a commonly used agent in treating hypertension and angina because
      of its vasodilator properties. An inhibitory role of nifedipine on aldosterone
      (Aldo) biosynthesis has been documented in in vitro studies. This study was
      designed to examine the impact of a sustained release nifedipine formulation on
      Aldo biosynthesis and its clinical consequences. Early and late effects of
      nifedipine on Aldo, PRA, and Aldo/PRA ratio levels were studied in a single
      blind, placebo-controlled, 10-day pilot study. Ten normotensive subjects and 10
      patients with hypertension were studied. Blood samples for the measurement of
      Aldo and PRA were obtained at 2-h intervals for 10 h on a control day and on days
      1 and 8 of nifedipine treatment for the determination of baseline, early, and
      late values. Placebo was administered at 0800 h on the first and second days of
      the study, whereas nifedipine (60 mg/day) was given for the following 8 days. The
      Aldo/ PRA ratio was used as a sensitive indirect index of the responsiveness of
      Aldo secretion to adrenal stimulation with angiotensin. Compared to those on the
      control day, a significant rise in the integrated PRA levels occurred on the
      first day of nifedipine treatment, with a further rise observed on the eighth day
      of the treatment in the normotensive subjects (1.1 +/- 0.6, 1.7 +/- 1.2, and 2.5
      +/- 1.8 ng/mL.h on the control day and the first and eighth days of treatment,
      respectively; P < 0.05) and by the eighth day in the hypertensive subjects (2.2
      +/- 2.8 and 4.0 +/- 4.1 ng/mL.h; P < 0.05). A significant rise in integrated Aldo
      levels occurred in the normotensive subjects on the eighth day of nifedipine
      treatment (control day, 319 +/- 187; eighth day of nifedipine, 363 +/- 167
      pmol/L; P < 0.05) and in the hypertensive subjects (426 +/- 219 and 535 +/- 284
      pmol/L; P < 0.05). This was associated with a significant lowering of the
      Aldo/PRA ratio on the first day of the treatment, with further lowering on the
      eighth day in the normotensive (435 +/- 454, 269 +/- 209, and 182 +/- 107; P <
      0.05) and by the eighth day in the hypertensive subjects (716 +/- 833 and 305 +/-
      315; P < 0.05). When individual time points were examined in the normotensive
      subjects, Aldo/PRA levels were significantly lower on day 8 of nifedipine
      treatment at 1000, 1200, and 1400 h than corresponding values on the control day.
      The fall in the Aldo/PRA ratio during nifedipine treatment indicates that the
      previously reported in vitro inhibition of Aldo biosynthesis in adrenal cells is
      reproduced in vivo. In the absence of nifedipine, it is likely that Aldo levels
      would be higher for any given level of PRA. It is probable that the Aldo
      inhibition and the vasodilatatory effect of nifedipine combine to bring about the
      lowering of blood pressure. Drugs that inhibit renin-angiotensin axis activity
      are likely to be particularly effective when additional lowering of blood
      pressure is required.

PMID- 9024237
TI  - Ovarian origin of plasma and peritoneal fluid prorenin in early pregnancy and in
      patients with ovarian hyperstimulation syndrome.
AB  - Prorenin is the major product of renin gene expression in the ovary. Plasma
      levels of prorenin are elevated in ovarian-stimulated patients and during early
      pregnancy. To further elucidate the source of the elevated plasma levels of
      prorenin, we measured prorenin, renin activity, angiotensinogen, and steroid
      hormone levels in the plasma, luteal fluids (luteal cysts), ascitic fluid, and in
      ovarian venous samples collected from a patient with severe ovarian
      hyperstimulation syndrome (OHSS) and ectopic pregnancy. Prorenin/renin was also
      measured in plasma and in peritoneal fluid obtained during, therapeutic
      paracentesis from four patients with OHSS. Several corpora luteal fluids were
      obtained that were rich in estradiol (E2) and progesterone (P). Ovarian venous E2
      and P were 20-fold higher than in arterial blood and as high or higher than the
      levels detected in the luteal fluids. The ratios of the hormonal levels in
      ascitic fluid and plasma were 1.9 for P and 1.4 for E2. A wide range of prorenin
      concentrations [1279 +/- 918 SD ng/mL/hr, n = 6] were found in corpora luteal
      fluids, but in each the prorenin concentration was higher than in plasma (494
      ng/mL/hr). Prorenin but not renin was higher (+23%) in ovarian venous than
      arterial blood. Prorenin in the 7 liters of ascitic fluid aspirated (2686
      ng/mL/hr) was 5-fold higher than in plasma and similar to the levels measured in
      the corpora lutea with the highest prorenin concentrations. Renin in luteal cysts
      and ascitic fluid constituted 3% and 6% of the total renin (renin+prorenin),
      respectively. Total renin was also higher in peritoneal fluid (1538 +/- 925
      ng/mL/hr) than in plasma (375 +/- 237 ng/mL/hr) of the 4 additional patients with
      severe OHSS. These findings indicate that the ovary secretes prorenin during
      early pregnancy and that its secretion is directed preferentially from the luteal
      cysts into the peritoneal cavity. In light of recent evidence of an effect of
      prorenin on the vascular system, the presence of a huge reservoir of prorenin in
      the peritoneal cavity of patients with OHSS suggests a potential role for
      prorenin in the pathogenesis of this syndrome.

PMID- 9024238
TI  - Cloning and expression of the glucocorticoid receptor from the squirrel monkey
      (Saimiri boliviensis boliviensis), a glucocorticoid-resistant primate.
AB  - New World primates such as the squirrel monkey have elevated cortisol levels and
      glucocorticoid resistance. We have shown that the apparent binding affinity of
      the glucocorticoid receptor in squirrel monkey lymphocytes is 5-fold lower than
      that in human lymphocytes (apparent Kd, 20.9 +/- 1.8 and 4.3 +/- 0.2 nmol/L,
      respectively; n = 3), consistent with previous studies in mononuclear leukocytes
      isolated from the two species. As a first step in understanding the mechanism of
      decreased binding affinity in New World primates, we used reverse transcription
      PCR to clone the glucocorticoid receptor from squirrel monkey liver and have
      compared the sequence to receptor sequences obtained from owl monkey liver,
      cotton-top tamarin B95-8 cells, and human lymphocytes. The squirrel monkey
      glucocorticoid receptor is approximately 97% identical in nucleotide and amino
      acid sequence to the human receptor. The ligand-binding domain (amino acids 528
      777) of the squirrel monkey glucocorticoid receptor contains four amino acid
      differences (Ser551 to Thr, Ser616 to Ala, Ala618 to Ser, and Ile761 to Leu), all
      of which are present in owl monkey and cotton-top tamarin receptors. The DNA
      binding domain (amino acids 421-486) is completely conserved among human,
      squirrel monkey, owl monkey, and cotton-top tamarin receptors. Twenty-two
      differences from the human sequence were found in the N-terminal region (amino
      acids 1-421) of the squirrel monkey receptor. None of the substitutions in the
      ligand-binding domain matched mutations known to influence binding affinity in
      other species. To determine whether the substitutions per se were responsible for
      decreased affinity, squirrel monkey and human glucocorticoid receptors were
      expressed in the TNT Coupled Reticulocyte Lysate System. Expressions of human and
      squirrel monkey glucocorticoid receptors and a squirrel monkey receptor in which
      Phe774 was mutated to Leu (F774L) were similar. When expressed in the TNT System,
      squirrel monkey and human glucocorticoid receptors had similar, high affinity
      binding for dexamethasone (apparent Kd, 5.9 +/- 1.2 and 4.3 +/- 0.5 nmol/L,
      respectively; n = 3), whereas the squirrel monkey F774L receptor had lower
      affinity binding (apparent Kd, 20.4 +/- 2.0 nmol/L; n = 3). Thus, substitutions
      within the ligand-binding domain of the squirrel monkey glucocorticoid receptor
      cannot account for the decreased binding affinity of these receptors in squirrel
      monkey cells. Rather, the binding affinity is probably influenced by the
      expression of cytosolic factors that affect glucocorticoid receptor function.

PMID- 9024239
TI  - Effects of glucagon-like peptide-1 on islet function and insulin sensitivity in
      noninsulin-dependent diabetes mellitus.
AB  - Administration of the truncated glucagon-like peptide 1 (GLP-1) has been
      considered for treatment of noninsulin-dependent diabetes mellitus (NIDDM). We
      studied its antidiabetogenic mechanism by examining its influences on islet
      function and peripheral insulin sensitivity in six subjects (aged 56-74 yr) with
      well-controlled NIDDM. Islet function was evaluated with arginine stimulation at
      three plasma glucose levels (fasting, 14 mmol/L, and > 28 mmol/L). GLP-1 (1.5
      pmol/kg per min iv) increased serum insulin levels at fasting glucose (P =
      0.028), at 14 mmol/L glucose (P = 0.028), and at 28 mmol/L glucose (P = 0.028).
      The acute insulin response (AIR) to 5 g iv arginine was increased by GLP-1 at 14
      mmol/L glucose (P = 0.028), and the slopeAIR, i.e., the glucose potentiation of
      insulin secretion, was markedly increased by GLP-1 (P = 0.028). Plasma glucagon
      levels were reduced by GLP-1 (P = 0.028), and arginine-stimulated glucagon
      secretion (AGR) was inhibited by GLP-1 at 14 (P = 0.046) and 28 mmol/L glucose (P
      = 0.028). Glucose-induced inhibition of arginine-stimulated glucagon secretion
      (slopeAGR) was not significantly affected by GLP-1. In contrast, GLP-1 did not
      affect the low insulin sensitivity during a hyperinsulinemic, euglycemic clamp.
      Thus, GLP-1 improves islet dysfunction in diabetes, mainly by increasing the
      glucose-induced potentiation of insulin secretion. In contrast, the peptide does
      not seem to improve insulin resistance in NIDDM.

PMID- 9024240
TI  - Carriers of 21-hydroxylase deficiency are not at increased risk for
      hyperandrogenism.
AB  - A deficiency of 21-hydroxylase activity is one of the most commonly inherited
      genetic disorders in man, with heterozygosity for CYP21 mutations affecting
      approximately 1 in 60 of the non-Jewish Caucasian population. We have
      hypothesized that heterozygosity for CYP21 mutations in women increases their
      risk of developing clinically evident hyperandrogenism, and that this risk is
      related to the severity of the mutation of CYP21 and/or the 17
      hydroxyprogesterone (17-OHP) response to ACTH stimulation. To test these
      hypotheses, we studied 38 obligate carriers for 21-hydroxylase deficiency (i.e.
      mothers of children with congenital adrenal hyperplasia or nonclassic congenital
      adreanl hyperplasia), comparing them to 27 weight-, parity-, and age-matched
      controls. Premenopausal carriers, not receiving hormonal treatment (n = 27), had
      higher mean total and free testosterone [T; 2.02 +/- 0.55 vs. 1.56 +/- 0.65
      nmol/L (P < 0.007) and 0.018 +/- 0.007 vs. 0.012 +/- 0.006 nmol/L (P < 0.007),
      respectively] and lower mean sex hormone-binding globulin (214 +/- 62 vs. 277 +/-
      129 nmol/L; P < 0.03) levels compared to controls. There was no difference in the
      mean basal levels of dehydroepiandrosterone sulfate, androstenedione (A4), or 17
      OHP between carriers and controls. As expected, carriers exhibited higher
      stimulated and net increment 17-OHP levels than controls [21.1 +/- 27.1 vs. 6.2
      +/- 3.1 nmol/L (P < 0.01) and 19.0 +/- 26.5 vs. 4.4 +/- 2.8 nmol/L (P < 0.009),
      respectively]. However, no difference was observed in the response of A4 to ACTH
      (1-24) stimulation. Of the 27 carriers studied biochemically, 2 (7.4%) had a
      stimulated 17-OHP value between 30.3-60.6 nmol/L, and 1 (3.7%) had a 17-OHP level
      above 60.6 nmol/L, suggestive of nonclassic adrenal hyperplasia. Of all carriers
      studied genetically (n = 36), 50.0% (18 of 36) had 1, 33% (12 of 36) had 2, and
      16.7% (6 of 36) had 3 or more mutations. In 27.8% (10 of 36) of carriers, the
      mutations were contiguous, consistent with a large gene conversion. All 38
      carriers were examined for historical and physical features of hyperandrogenism.
      Hirsutism was defined as a Ferriman-Gallwey score of 6 or more,
      menstrual/ovulatory dysfunction as a history of menstrual cycles of more than 35
      day, and hyperandrogenemia as total or free T, A4, and/or dehydroepiandrosterone
      sulfate levels above the upper 95th percentile of control values. Further,
      defining functional androgen excess (FAE) as the presence of at least 2 of the 3
      hyperandrogenic features, 4 of 38 (10.5%) of carriers appeared to be affected
      (95% confidence interval, 2.9-24.8%). Assuming an expected prevalence rate of FAE
      in the general population of 5-20%, the frequency of FAE among our carriers was
      not significantly higher than expected. In conclusion, heterozygosity for CYP21
      mutations does not appear to increase the risk of clinically evident
      hyperandrogenism, although carrying the defect was associated with higher mean
      and free T levels. Finally, due to the low frequency of androgen excess in our
      heterozygote population, we were unable to correlate the severity of the CYP21
      mutation and/or the 17-OHP response to ACTH stimulation with the presence of the
      phenotype.

PMID- 9024241
TI  - A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating
      frequent expression of pituitary tumors but not linked to the multiple endocrine
      neoplasia type 1 locus at chromosome region 11q13.
AB  - Acromegaly is uncommon in kindreds with multiple endocrine neoplasia type 1
      (MEN1), whereas primary hyperparathyroidism (PHP) has the highest penetrance of
      any endocrinopathy. We report an unusual MEN1 kindred with frequent expression of
      pituitary tumors and a low penetrance of PHP. Four members were found to have
      disease: PHP in generation I, acromegaly (2 cases) in generation II, and
      hyperprolactinemia associated with a pituitary tumor in generation III. There was
      no evidence for PHP in 1 patient with acromegaly (age 60 yr), the patient with
      hyperprolactinemia and the pituitary tumor (age 22 yr), and 1 asymptomatic
      obligate carrier (age 50 yr). Screening of 26 members revealed the possible
      diagnosis of PHP in 1 family member in generation II and possible early
      acromegaly in 2 members of generation III with elevated serum concentrations of
      insulin-like growth factor I and insulin-like growth factor-binding protein-3 but
      normal patterns of pulsatile GH release. Although the predisposing genetic defect
      in typical MEN1 families has previously been mapped to chromosome location 11q13
      without evidence of heterogeneity among the 87 families analyzed, linkage of
      disease in this family to the MEN1 region is unlikely based on haplotype
      analysis. Localization of the gene(s) responsible for disease in such atypical
      families may aid in the understanding of the pathogenesis of MEN1. In addition,
      further study of the earliest changes in patterns of pulsatile GH release in
      familial acromegaly may allow more insight into the pathogenesis and natural
      history of this disease.

PMID- 9024242
TI  - G protein and thyrotropin receptor mutations in thyroid neoplasia.
AB  - The cAMP pathway plays a central role in thyroid follicular cell growth and
      function. Mutations of the TSH receptor (TSHR) or G proteins (gsp) that activate
      adenylyl cyclase have been identified in autonomously functioning thyroid
      nodules. Gsp mutations have been identified also in other forms of thyroid
      neoplasia, but their reported prevalence has been extremely variable. We have
      studied the prevalence of gsp mutations and activating mutations of Gi2 alpha
      (gip) in a series of 66 benign and 34 malignant thyroid tumors. Thirty-six tumors
      were from Boston and 64 from the UK. In addition, we examined the 64 UK tumors
      for mutations of the TSHR gene. DNA extracted from fresh-frozen or paraffin
      embedded tissue was amplified by PCR and examined for mutations using
      oligonucleotide-specific hybridization and single-strand conformation
      polymorphism analysis. No G protein gene mutations were identified in the Boston
      tumors. One gsp mutation, R201C, in a Hurthle cell adenoma and 1 gip mutation,
      R179C, in a follicular adenoma were demonstrated in tumors from the UK.
      Oligonucleotide-specific hybridization and single-strand conformation
      polymorphism analysis of the UK tumors did not demonstrate any mutations of the
      TSHR gene. Eleven normal thyroid tissue samples were wild-type for Gs alpha, Gi2
      alpha, and the TSHR gene.

PMID- 9024243
TI  - Short-term hyperthyroidism has no effect on leptin levels in man.
AB  - Leptin, a 16-kDa adipocyte-derived protein whose circulating levels reflect
      energy stores, increases the resting metabolic rate and thermogenesis in rodents.
      Thyroid hormones also increase the basal metabolic rate, but nothing is known
      about possible interactions between leptin and thyroid hormone. Activation of
      beta-adrenergic receptors decreases leptin levels in rodents. To test the
      hypothesis that thyroid hormones, by causing a "functional hyperadrenergic"
      state, result in decreased leptin concentrations in humans, we studied 22 normal
      healthy men before and after the administration of T3 for 1 week to induce
      moderate hyperthyroidism. Short term thyroid hormone excess does not alter
      circulating leptin concentrations despite a demonstrated effect on heart rate,
      systolic blood pressure, cholesterol levels, and metabolic indexes of bone
      turnover. Elucidation of the apparently separate pathways by which thyroid
      hormones, beta-agonists, and leptin regulate energy expenditure and food intake
      may have important implications for our understanding of the mechanisms for
      regulating energy homeostasis in health and disease.

PMID- 9024244
TI  - Thyrotropin receptor autoantibodies in serum are present at much lower levels
      than thyroid peroxidase autoantibodies: analysis by flow cytometry.
AB  - Using Chinese hamster ovary (CHO) cells that express high numbers of TSH receptor
      (TSHR) on their surface, we studied the feasibility of detecting directly by flow
      cytometry the binding of autoantibodies in patients' sera to the native TSHR.
      After using a serum (BBI) with high potency in the TSH binding inhibition (TBI)
      assay to establish the protocol, we studied an additional 38 sera: 10 without TBI
      activity (1-4.2% inhibition), 10 with moderately high TBI values (17.3-39.4%
      inhibition), 10 with high TBI levels (52-95.1% inhibition), 4 from normal
      individuals without autoimmune thyroid disease, and 4 from patients with systemic
      lupus erythematosus. We observed that a number of sera, including some without
      thyroid autoantibodies, contain antibodies against unknown antigens on CHO cells.
      Preadsorption with untransfected CHO cells before addition to the TSHR-10,000
      cells eliminated or greatly reduced this nonspecific background. None of the sera
      from normal individuals, subjects with negative TBI values, or patients with
      systemic autoimmunity generated a positive signal on flow cytometry with TSHR
      10,000 cells relative to the signal on untransfected cells. Remarkably, only 4 of
      21 TBI-positive sera (including BBI) unequivocally recognized the TSHR on flow
      cytometry. In contrast, when thyroid peroxidase (TPO) autoantibodies in the same
      sera were studied using CHO cells overexpressing TPO on their surface, all 20
      sera with TPO autoantibodies clearly elicited positive net fluorescence relative
      to untransfected cells. Study of the potent serum, BBI, revealed similar
      fluorescence (approximately 250 U) for TPO autoantibodies and TSHR autoantibodies
      at dilutions of 1:1000 and 1:10, respectively. Thus, by flow cytometry, the titer
      of TPO autoantibodies in the BBI serum is about 100-fold higher than that for
      TSHR autoantibodies in the same serum. In conclusion, the present data provide
      the strongest support for the idea that TSHR autoantibodies in the sera of
      patients with autoimmune thyroid disease are present at much lower levels than
      are TPO autoantibodies. This finding has important implications for the
      diagnostic detection of TSHR autoantibodies and for understanding the
      pathogenesis of Graves' disease.

PMID- 9024245
TI  - In vitro expression of endothelin-1 (ET-1) and the ETA and ETB ET receptors by
      the prostatic epithelium and stroma.
AB  - RT-PCR analysis of total RNA prepared from the prostate cancer cell lines DU145
      and PC3 and from primary epithelial cells indicated the presence of endothelin-1
      (ET-1) messenger RNA (mRNA). Neither the LNCaP cell line nor primary prostatic
      stromal cells possess ET-1 mRNA transcripts. Seventy-two-hour-conditioned media
      derived from DU145, PC3, and primary epithelia contain immunoreactive ET
      concentrations equivalent to 0.814 +/- 0.048, 0.330 +/- 0.050, and 0.856 +/-
      0.055 fmol/mL/10(6) cells after 72 h, respectively. Basal immunoreactive ET
      secretion was exhibited by LNCaP (0.029 +/- 0.009 fmol/mL/10(6) cells after 72 h)
      and stromal cells (0.067 +/- 0.007 fmol/ mL/10(6) cells after 72 h). Examination
      of ETA and ETB gene expression by RT-PCR demonstrates that ET receptor mRNA is
      almost completely undetectable in the prostate cancer cell lines. Both ETA and
      ETB mRNAs are detectable in primary cultures of prostatic epithelia and stroma.
      Competitive binding studies demonstrate a single class of binding site in both
      primary benign epithelia (dissociation constant = 1.85 x 10(-10) mol/L; maximal
      binding capacity = 2.7 x 10(4) binding sites/cell), and stroma (dissociation
      constant = 1.93 x 10(-10) mol/L; maximal binding capacity = 3.7 x 10(5) binding
      sites/cell). Use of selective ET receptor antagonists confirmed that the
      predominant stromal receptor subtype expressed in vitro is ETB. This receptor
      seems not to be coupled to mitogenic pathways because no growth response to
      exogenous ET-1 or cooperation between ET-1 and bFGF could be observed. Similarly,
      no effect of ET-1 or the ET-converting enzyme inhibitor, phosphoramidon, on
      benign epithelial cells could be observed over a 4-day period.

PMID- 9024247
TI  - Effect of different dopaminergic agents in the treatment of acromegaly.
AB  - Medical treatment of acromegaly with dopamine agonists possesses 2 main
      advantages: the oral administration and the low costs. In this study, we reported
      on the results of chronic treatments with quinagolide (CV 205-502), cabergoline
      (CAB) and long-acting depot preparation of bromocriptine (BRC-LAR) in 34
      acromegalics. Patients were divided into three groups on the basis of different
      treatment: CV 205-502 given to 16 patients at the dose of 0.3-0.6 mg/day for 6
      months; CAB given to 11 patients at the dose of 1.0-2.0 mg weekly for 6 months;
      and BRC-LAR injected into 7 patients at the dose of 100 mg/month for 6-12 months.
      Basal and oral glucose tolerance test-stimulated serum GH levels, basal and TRH
      stimulated PRL levels, plasma insulin-like growth factor I (IGF-I) levels,
      computed tomography scan, and/or magnetic resonance imaging were assessed before
      and quarterly during treatments. The chronic administration of CV 205-502, CAB,
      and BRC-LAR caused a significant decrease of circulating GH, IGF-I, and PRL
      levels (P < 0.005). Normalization of circulating GH and IGF-I levels was obtained
      in 7 of 16 (43.8%) patients treated with CV 205-502. Serum GH response to oral
      glucose tolerance test (oGTT) significantly improved (P < 0.005), and PRL levels
      were significantly suppressed during treatments. No correlation was found between
      basal and TRH-stimulated PRL levels and GH suppression during different
      therapies. Immunohistochemical staining revealed 19 GH-positive and 10 GH + PRL
      positive adenomas. A significant association was found between GH/PRL staining
      and responsiveness to chronic treatments (chi 2 = 7.985, P < 0.005). Three
      patients had significant adenoma shrinkage. Slight nausea and hypotension which
      spontaneously disappeared within therapy progression, were referred by 5/16
      patients during CV 205-502 and 2/7 during BRC-LAR. The results of this study
      indicate that CAB and BRC-LAR cannot be considered as useful medical approaches
      for acromegalics, whereas CV 205-502 normalized circulating GH and IGF-I levels
      in 47.8% of patients.

PMID- 9024246
TI  - Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma
      adrenocorticotropin secretion in Nelson's syndrome.
AB  - Previous studies have found that bromocriptine, cyproheptadine, and valproic acid
      can reduce ACTH secretion in Nelson's syndrome, but none of these agents has
      achieved widespread use due to their failure to normalize ACTH in most patients.
      The current study was undertaken to determine whether these three agents, which
      act through different mechanisms, decrease plasma ACTH synergistically when
      administered together. Six adult female patients (mean age, 41 yr) with Nelson's
      syndrome were studied. ACTH was measured every 20 min for 8 h, 2 h before and 6 h
      after each of the following six treatments: placebo, bromocriptine (2.5 mg),
      cyproheptadine (8 mg), valproic acid (1 g), cyproheptadine plus valproic acid,
      and the combination of all three drugs. The sequence of treatments was determined
      randomly, and there was an interval of at least 2 days between each treatment.
      The hourly ACTH values were averaged, and the percent maximal suppression of
      plasma ACTH, relative to the baseline values before drug administration, was
      compared among the six treatments. Basal plasma ACTH levels in the six patients
      ranged from 40-3324 pmol/L (normal range, 1-8). The percent maximal suppression
      of ACTH after administration of placebo (6 +/- 11%), cyproheptadine (17 +/- 15%),
      valproic acid (37 +/- 10%) or the combination of cyproheptadine and valproic acid
      (19 +/- 14%) did not achieve statistical significance. Bromocriptine, on the
      other hand, caused a significant decrease in plasma ACTH (52 +/- 8%; P < 0.05),
      as did the combination of bromocriptine, cyproheptadine, and valproic acid (58 +/
      12%; P < 0.05). However, the combined effect of the three drugs did not
      significantly exceed the effect of bromocriptine alone. We conclude that at the
      doses studied, bromocriptine had the greatest acute effect in suppressing ACTH
      secretion in Nelson's syndrome, and that combined administration with valproic
      acid and cyproheptadine did not further increase this acute ACTH-suppressive
      effect.

PMID- 9024248
TI  - Effects of metformin on insulin secretion, insulin action, and ovarian
      steroidogenesis in women with polycystic ovary syndrome.
AB  - Hyperinsulinemia contributes to the ovarian androgen overproduction and glucose
      intolerance of polycystic ovary syndrome (PCOS). We sought to determine whether
      metformin would reduce insulin levels in obese, nondiabetic women with PCOS
      during a period of weight maintenance and thus attenuate the ovarian
      steroidogenic response to the GnRH agonist leuprolide. All subjects (n = 14) had
      an oral glucose tolerance test, a GnRH agonist (leuprolide) test, a frequently
      sampled iv glucose tolerance test, graded and oscillatory glucose infusions, and
      a dual energy x-ray absorptiometry scan before and after treatment with metformin
      (850 mg, orally, three times daily for 12 weeks). With weight maintenance (body
      mass index: pretreatment, 39.0 +/- 7.7 kg/m2, posttreatment, 39.1 +/- 7.9 kg/m2),
      oral glucose tolerance, insulin sensitivity (Si; 0.87 +/- 0.82 vs. 0.74 +/- 0.63
      x 10(-5) min-1/ pmol.L), and the relationship between Si and first phase insulin
      secretion (AIRg vs. Si) were not improved by metformin. The insulin secretory
      response to glucose, administered in both graded and oscillatory fashions, was
      likewise unaltered in response to metformin. Free testosterone levels remained
      about 2-fold elevated (pretreatment, 26.6 +/- 12.7 pg/mL; posttreatment, 22.4 +/-
      9.8 pg/mL). Both basal and stimulated LH and FSH levels were unaffected by
      metformin. The mean responses to leuprolide of 17-hydroxyprogesterone
      (pretreatment, 387 +/- 158 ng/dL; posttreatment, 329 +/- 116 ng/dL) as well as
      those of the other ovarian secretory products (androstenedione,
      dehydroepiandrosterone, progesterone, and estradiol) were not attenuated by
      metformin. We conclude that hyperinsulinemia and androgen excess in obese
      nondiabetic women with PCOS are not improved by the administration of metformin.

PMID- 9024249
TI  - Biochemical tests in the diagnosis of childhood growth hormone deficiency.
AB  - GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD),
      although they are associated with a high false positive rate. We have examined,
      therefore, the performance of other tests of the GH axis [urinary GH excretion,
      serum insulin-like growth factor I(IGF-I), and IGF-binding protein-3 (IGFBP-3)
      levels] compared with GH stimulation tests in identifying children defined
      clinically as GH deficient. Group I comprised 60 children (mean age, 10.3 +/- 4.8
      yr) whose diagnosis of GHD was based on a medical history indicative of pituitary
      dysfunction (n = 43) or on the typical phenotypic features and appropriate
      auxological characteristics of isolated GHD (n = 17). Group II comprised 110
      short children (mean age, 9.8 +/- 4 yr) in whom GHD was not suspected, but needed
      exclusion. The best sensitivity for a single GH test was 85% at a peak GH cut-off
      level of 10 ng/mL, whereas the best specificity was 92% at 5 ng/mL. The
      sensitivities of IGF-I, IGFBP-3, and urinary GH, using a cut-off of -2 SD score
      were poor at 34%, 22%, and 25%, respectively, with specificities of 72%, 92%, and
      76% respectively. Only 2 of 21 pubertal children in group I and none of the 27
      subjects with radiation-induced GHD had an IGFBP-3 SD score less than -1.5. We
      devised a scoring system based on the positive predictive value of each test,
      incorporating data from the GH test and the IGF-I and IGFBP-3 levels. A
      specificity of 94% could be achieved with a score of 10 or more (maximum 17)
      (sensitivity 34%). The latter could not be improved above 81% with a score of 5
      points or more (specificity, 69%). A high score was, therefore, highly indicative
      of GHD, but was achieved by few patients. A normal IGFBP-3 level, however, did
      not exclude GHD, particularly in patients with radiation-induced GHD and those in
      puberty. A GH test with a peak level more than 10 ng/mL was the most useful
      single investigation to exclude a diagnosis of GHD.

PMID- 9024250
TI  - Circadian cortisol rhythms in healthy boys and girls: relationship with age,
      growth, body composition, and pubertal development.
AB  - To provide basic information on the normal functioning of the hypothalamus
      pituitary-adrenal axis in relation to pubertal development, growth (weight and
      height), body composition, and gender and to obtain reference data for serum
      cortisol concentrations in children, we investigated the basal circadian rhythm
      of serum cortisol in a group of 235 healthy children (162 boys and 73 girls). The
      age range was between 2.2-18.5 yr. Serum cortisol was analyzed from venous blood
      samples taken at 1400, 1800, 2200, 0200, 0400, 0600, and 1000 h. No evidence was
      found for differences in temporal placement or level of the circadian cortisol
      rhythm in relation to age, growth, or body composition. However, we found a broad
      range of cortisol levels in a healthy population, with individual mean diurnal
      levels ranging from 100-510 nmol/L. Regardless of high or low mean diurnal
      cortisol levels, repeated measurements within and between pubertal stages
      indicated that an individual remains in his or her cortisol range throughout
      pubertal development. In conclusion, the present study shows that 1) serum
      cortisol levels do not correlate with either age or gender; 2) there is a large
      and significant interindividual variability in endogenous mean diurnal cortisol
      levels; and 3) despite this variability between individuals, there is no
      correlation between cortisol levels and either body composition or growth rate.
      This suggests that the variability in cortisol levels is an expression of normal
      homeostasis rather than pathology.

PMID- 9024251
TI  - Twenty-four-hour profiles of luteinizing hormone, follicle-stimulating hormone,
      testosterone, and estradiol levels: a semilongitudinal study throughout puberty
      in healthy boys.
AB  - To follow and correlate gonadotropin and sex steroid changes throughout puberty,
      24-h profiles of LH, FSH, testosterone, and estradiol were taken on several
      occasions for between 2-9.5 yr in 12 healthy boys, aged 8.7-18.2 yr. Serum
      concentrations of LH and FSH were measured every 20 min, whereas testosterone and
      estradiol were measured every 2-4 h during the 24-h period. The prepubertal boys
      (Tanner stage 1) were subdivided into two groups: Pre 1, with a testicular volume
      of 1-2 mL, and Pre 2, with a testicular volume of 3 mL. Pubertal stages were
      classified, according to testicular volume, as early puberty (pubertal stage 2; 4
      9 mL), midpuberty (pubertal stages 3-4; 10-15 mL), and late puberty (pubertal
      stage 5; > or = 16 mL). Mean levels of LH and FSH increased with pubertal
      development, although the increase in LH was greater than that in FSH. These
      increases were due to elevated basal levels of LH and FSH as well as to increases
      in the number of peaks and the peak amplitudes of LH. No diurnal rhythm was found
      in boys at stage Pre 1. Thereafter, a clear diurnal rhythm appeared for LH, and
      later in puberty, an ultradian rhythm was superimposed, as shown by time-sequence
      analyses. A diurnal rhythm also existed for FSH, but was much less marked than
      that for LH despite a clear covariation between LH and FSH, as shown from cross
      correlation studies. Testosterone also showed diurnal variations from the late
      prepubertal stage, followed by increasing levels during both day and night in
      puberty. We conclude that during puberty, gonadotropin levels rise differently
      for LH and FSH, which may be due to the development of differences in feedback
      mechanisms. Despite covariation between LH and FSH, only LH showed a clear
      diurnal variation. In parallel, nocturnal variations in testosterone and
      estradiol were found. Changes in mean levels of LH, testosterone, and estradiol
      as well as their mean daytime and nighttime levels follow each other from the
      prepubertal stages to late puberty.

PMID- 9024252
TI  - Growth hormone (GH)-deficient men are more responsive to GH replacement therapy
      than women.
AB  - Thirty-six patients with adult-onset GH deficiency (GHD) were examined before and
      after 9 months of treatment with recombinant GH. The study was conducted as a
      double blind, placebo-controlled, 21-month trial with a cross-over design, with
      each treatment period lasting for 9 months. The same dose, adjusted for body
      surface area, was given to men (n = 21) and women (n = 15), and the effects on
      body composition and biochemical parameters were evaluated with respect to
      gender. The extent of GHD, assessed before therapy from basal GH secretion and GH
      release in response to provocative tests, did not differ between the two groups.
      The men, however, had higher serum insulin-like growth factor I concentrations
      than the women (mean +/- SD, 126 +/- 71 vs. 61 +/- 32 micrograms/L; P = 0.0003),
      less body fat, and greater lean body mass. Upon treatment, insulin-like growth
      factor I concentrations increased more in men than in women (by 305 +/- 136 and
      198 +/- 96 micrograms/L, respectively; P = 0.02). The men lost more body fat than
      the women (7.4 +/- 4.1% vs. 3.3 +/- 3.8%; P = 0.002), whereas the difference in
      gain in lean body mass failed to reach statistical significance. Serum levels of
      total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, and
      plasminogen activator inhibitor-1 decreased in the male group (P = 0.003, P =
      0.03, P = 0.0009, and P = 0.01, respectively), but not in the females. Serum
      markers of bone formation, namely osteocalcin, procollagen type I, bone-specific
      alkaline phosphatase, and a marker of bone resorption, telopeptide of collagen
      type I, increased more markedly in men than in women. Lipoprotein(a) increased to
      a similar extent in the male and female groups. The data demonstrate that men and
      women with GHD display marked differences in their responsiveness to GH
      replacement therapy. These differences should be taken into consideration when
      optimizing the treatment of GHD patients.

PMID- 9024253
TI  - 17 alpha-Hydroxyprogesterone responses to leuprolide and serum androgens in obese
      women with and without polycystic ovary syndrome offer dietary weight loss.
AB  - Insulin resistance and increased ovarian cytochrome P450c17 alpha activity (i.e.
      increased 17 alpha-hydroxylase and, to a lesser extent, increased 17,20-lyase)
      are both features of the polycystic ovary syndrome (PCOS). Evidence suggests that
      hyperinsulinemia may stimulate ovarian P450c17 alpha activity in obese women with
      PCOS. We hypothesized that weight loss would decrease serum insulin and P450c17
      alpha activity in PCOS. Therefore, we measured serum steroid concentrations and
      17 alpha-hydroxyprogesterone responses to leuprolide administration and performed
      oral glucose tolerance tests before and after 8 weeks of a hypocaloric diet in 12
      obese women with PCOS (PCOS group) and 11 obese women with normal menses (control
      group). Serum insulin decreased in both groups. In the PCOS group, basal serum 17
      alpha-hydroxyprogesterone decreased from 4.2 +/- 0.6 to 3.0 +/- 0.5 nmol/L (P <
      0.05), and leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone
      decreased from 14.9 +/- 2.6 to 8.9 +/- 0.8 nmol/L (P < 0.025). Serum testosterone
      decreased from 2.47 +/- 0.52 to 1.56 +/- 0.33 nmol/L (P < 0.05), and free
      testosterone decreased from 9.03 +/- 1.39 to 5.95 +/- 0.50 pmol/L (P < 0.02).
      None of these values changed in the control group. Serum sex hormone-binding
      globulin increased by 4.5- and 3-fold in the PCOS (P < 0.003) and control (P <
      0.007) groups, respectively. We conclude that dietary weight loss decreases
      ovarian P450c17 alpha activity and reduces serum free testosterone concentrations
      in obese women with PCOS, but not in obese ovulatory women. The changes in women
      with PCOS may be related to a reduction in serum insulin.

PMID- 9024254
TI  - Effect of fasting, refeeding, and dietary fat restriction on plasma leptin
      levels.
AB  - The factors responsible for the variability in plasma leptin levels observed
      among individuals with similar body compositions remain unclear. To examine the
      impact of dietary variables, we compared the changes in leptin levels induced by
      fasting and dietary fat restriction with the expected decrease following a
      significant loss in adipose mass. A 21.4 +/- 3.7% weight loss led to a 76.3 +/-
      8.1% decrease in mean plasma leptin level (25.2 +/- 9.3 to 6.1 +/- 3.4 ng/mL, P =
      0.0001) in a group of 9 obese males. Despite a weight loss of only 2.6 +/- 0.8%,
      mean plasma leptin levels fell by 61.9 +/- 25.2% (8.5 +/- 4.5 to 2.4 +/- 0.5
      ng/mL, P < 0.01) in 7 nonobese females subjected to 3 days of fasting. Leptin
      levels in fasted subjects returned to baseline within 12 h of refeeding.
      Individual high- and low-fat meals given to 19 subjects after an overnight fast
      had no effect on plasma leptin levels. Reduction in dietary fat content from 37
      10% of total calories for 7 weeks was also without effect on plasma leptin levels
      in these subjects. We conclude that plasma leptin levels primarily reflect total
      adipose mass, rather than meal consumption or dietary energy source, but that the
      reduction in leptin levels with ongoing fasting is disproportionate to the
      reduction in adipose mass. The ability of fasting to deactivate this presumed
      physiological satiety system may have been advantageous in environments
      characterized by rapid changes in food availability.

PMID- 9024255
TI  - Effect of regional fat distribution and Prader-Willi syndrome on plasma leptin
      levels.
AB  - Variability in the relationship of plasma leptin level to body mass index (BMI)
      could be caused by imperfect estimation of adipose mass by the BMI, heterogeneity
      in the pathogenesis of obesity in mixed subject groups, or variation in adipose
      tissue distribution. To investigate these possibilities, we examined the
      correlation of plasma leptin and BMI in an ethnically mixed population, a group
      of subjects with the Prader-Willi syndrome, and a group of Japanese-American
      subjects who underwent computerized tomographic measurement of adipose tissue
      cross-sectional areas. Highly significant and indistinguishable linear
      relationships between plasma leptin levels and BMI were found in the three study
      groups. Intersubject variability was also similar in the three groups and was
      reduced only when more accurate techniques for assessing adipose tissue mass were
      substituted for the BMI. The plasma leptin level of Japanese-American subjects in
      the highest quartile of intraabdominal fat area (mean area = 154.5 +/- 38.4 cm2)
      was 12.5 +/- 8.7 ng/mL as compared to 12.3 +/- 9.6 ng/mL (P = 0.91) for subjects
      in the lowest quartile of intraabdominal fat area (mean area = 51.2 +/- 20.1 cm2,
      P < 0.001 for difference in fat areas). We conclude that the circulating leptin
      level reflects total adipose tissue mass rather than a combination of adipose
      tissue mass and distribution, and that the Prader-Willi syndrome does not alter
      the relationship between these two variables.

PMID- 9024256
TI  - Effects of age and sex hormones on transition and peripheral zone volumes of
      prostate and benign prostatic hyperplasia in twins.
AB  - Benign prostatic hyperplasia has been shown to increase with age and be
      influenced by sex hormones. The relationship between aging and hormonal
      influences on growth of zones of the prostate is unresolved. We studied the
      relationship of age and sex hormones on volume of prostate zones in 214 male
      twins between 25 and 75 yr old. Volumes of the total prostate (TV), transition
      zone (TZ), and peripheral zones (PZ) were measured using transrectal ultrasound,
      and sex steroid concentrations were measured using RIA. Using transformed data
      corrected for age, TV (r = 0.54, P < 0.00001), TZ (r = 0.58, P < 0.00001), and PZ
      (r = 0.39, P < 0.00001) volumes increased with age. However, the PZ volume rose
      more rapidly than the TZ before age 50, and TZ showed a steeper increase after
      age 50 yr than the PZ volume. The TZ, PZ, and ratio TZ/PZ correlated
      significantly (r = 0.87, 0.90, and 0.52, respectively; P < 0.00001). After a TV
      exceeded 30 g, the rise of the PZ became attenuated, and the slope of the TZ
      became steeper. Age-adjusted sex hormone concentration was not evaluated in men
      with larger prostate volumes. Men with American Urological Association symptom
      scores above 10 had significantly (P < 0.001) larger total prostate volume (TV)
      and TZ volume, but not PZ volumes, than men with scores below 10. Prostate
      volumes correlated inversely with age-adjusted serum testosterone (T),
      dihydrotestosterone, sex hormone binding globulin, and sex hormone binding
      globulin-bound T concentrations. These results demonstrate that before age 50 yr
      or before a prostate weight exceeds 30 g, prostate growth may be mainly from
      enlargement of the PZ and after age 50, the TZ. In addition, elevated T and
      dihydrotestosterone concentrations do not predispose men to prostate enlargement
      or symptoms of benign prostatic hyperplasia.

PMID- 9024257
TI  - Cross genotype sex hormone treatment in two cases of hypogonadal osteoporosis.
AB  - BACKGROUND: Sex hormone deficiency is the most common cause of bone loss. Reduced
      bone mass and an increased risk for osteoporotic fractures have been described in
      hypogonadal subjects of both sexes. We present here the results of treating two
      patients showing abnormal sexual differentiation (an XX male and an XY female),
      who suffered from bone loss related to sex hormone deficiency, with cross
      genotype sex hormones. SUBJECTS AND METHODS: Patient 1 was an asymptomatic 39-yr
      old XY female with complete androgen insensitivity. Her testes had been removed,
      and she later discontinued estrogen treatment. Patient 2, a 37-yr-old XX male,
      had congenital adrenal hyperplasia, which led to a masculine phenotype. He was
      ovariectomized and reared as a male. He was treated with glucocorticoids but
      refused androgen treatment for many years. We treated both patients with
      phenotypically matched sex hormones (patient 1 received conjugated estrogens 1.25
      mg/day, and patient 2 received 250 mg testosterone every 4 weeks) and followed
      their bone mineral density (BMD) using dual-energy X-ray absorptiometry, urine
      calcium, and hydroxyproline excretion. RESULTS: Before treatment both patients
      had low sex hormones and highly elevated gonadotropins. As a result of treatment
      urine hydroxyproline excretion decreased from 45 and 26.7 mg/g creatinine to 15
      and 15.9 mg/g creatinine in patients 1 and 2 respectively. In patient 1, lumbar
      BMD rose from 0.912gr/cm2 to 0.976gr/cm2 and femoral neck BMD rose from
      0.716gr/cm2 to 0.836gr/cm2 after 4 years of treatment. In patient 2, lumbar BMD
      rose from 0.717gr/cm2 to 0.815gr/cm2 and the femoral neck BMD rose from
      0.509gr/cm2 to 0.635gr/cm2 after 27 months of treatment. CONCLUSIONS:
      Phenotypically-matched sex hormone therapy in patients with abnormal sexual
      differentiation is essential not only to maintain external appearance but also
      for the preservation of bone mass.

PMID- 9024258
TI  - Sexual dimorphism in plasma leptin concentration.
AB  - Leptin, the obese (ob) gene product, is thought to be a lipostatic hormone that
      contributes to body weight regulation through modulating feeding behavior and/or
      energy expenditure. The determinants of plasma leptin concentration were
      evaluated in 267 subjects (106 with normal glucose tolerance, 102 with impaired
      glucose tolerance, and 59 with noninsulin-dependent diabetes). Fasting plasma
      leptin levels ranged from 1.8-79.6 ng/mL (geometric mean, 12.4), were higher in
      the obese subjects, and were not related to glucose tolerance. Women had
      approximately 40% higher leptin levels than men at any level of adiposity. After
      controlling for body fat, postmenopausal women had still higher leptin levels
      than men of similar age, and their levels were not different from those in
      younger women. Multiple regression analysis showed that adiposity, gender, and
      insulinemia were significant determinants of leptin concentration, explaining
      42%, 28%, and 2% of its variance, respectively. Neither age nor the waist/hip
      ratio was significantly related to leptin concentration. Thus, our data indicate
      that gender is a major determinant of the plasma leptin concentration. This sex
      difference is not apparently explained by sex hormones or body fat distribution.
      Leptin's sexual dimorphism suggests that women may be resistant to its putative
      lipostatic actions and that it may have a reproductive function.

PMID- 9024259
TI  - Leptin in human reproduction: serum leptin levels in pregnant and lactating
      women.
AB  - Experiments in ob/ob female mice demonstrated that leptin injections not only
      reduced weight and fat mass, but also restored fertility and partial lactation.
      To explore factors regulating ob gene expression in reproductive women, we
      measured serum leptin, body fat, energy expenditure, and milk production in 65
      women at 36 weeks of gestation, and at 3 and 6 months postpartum. Serum leptin
      was measured by solid-phase sandwich enzyme immunoassay, and serum insulin and
      PRL by solid-phase 125I RIA. Total body water by deuterium dilution, body volume
      by hydrodensitometry, and bone density by dual-energy x-ray absorptiometry were
      used to estimate body fat. Serum leptin per unit fat mass was significantly
      higher at 36 weeks of pregnancy than at 3 and 6 months postpartum (1.25 vs. 0.75,
      0.73 ng.mL-1.kg-1). Postpartum normalization of leptin was associated with
      changes not only in weight and fat mass, but also serum insulin. Leptin was not
      different between lactating and nonlactating women. Leptin may have affected milk
      production indirectly through its negative effect on serum PRL. Adjusted for fat
      free mass and fat mass, rates of energy expenditure were not significantly
      correlated with leptin. Our results provide evidence that factors other than fat
      mass alone modulate serum leptin in reproductive women.

PMID- 9024260
TI  - The somatotropic axis in critical illness: effect of continuous growth hormone
      (GH)-releasing hormone and GH-releasing peptide-2 infusion.
AB  - Prolonged critical illness is characterized by protein hypercatabolism and
      preservation of fat depots, associated with blunted GH secretion, elevated serum
      cortisol levels, and low insulin-like growth factor I (IGF-I) concentrations. In
      this condition, GH is readily released in response to a bolus of GHRH and GH
      releasing peptide-2 (GHRP-2) and, paradoxically, to TRH. We further explored the
      altered somatotropic axis and cortisol secretion in critical illness by examining
      the effects of continuous GHRH and/or GHRP-2 infusion. Twenty-six critically ill
      adults (mean age +/- SEM, 63 +/- 2 yr) were studied during 2 consecutive nights
      (2100-0600 h). According to a weighed randomization, they received one of four
      combinations of infusions within a randomized cross-over design for each
      combination: placebo (one night) and GHRP-2 (the other night; n = 10), placebo
      and GHRH (n = 4), GHRH and GHRP-2 (n = 6), and GHRP-2 and GHRH plus GHRP-2 (n =
      6). The peptide infusions (duration, 21 h) were started after a bolus of 1
      microgram/kg at 0900 h and infused (1 microgram/kg/h) until 0600 h. Serum
      concentrations of GH were determined every 20 min, cortisol every hour, and IGF-I
      at 2100 and 0600 h on each study night. The placebo profiles showed pulsatile GH
      secretion with low secretory burst amplitude [0.062 +/- 0.008 microgram/L
      distribution volume (Lv)/min], high burst frequency (6.6 +/- 0.4 events/9 h), and
      detectable basal secretion (0.041 +/- 0.009 microgram/L/min) in the face of low
      serum IGF-I (106 +/- 11 micrograms/L). IGF-I correlated positively and
      significantly with the basal component, the pulsatile component, and the total
      amount of nightly GH secretion. GHRH elicited a 2- to 3-fold increase in the mean
      GH concentration (P = 0.006), the GH secretory burst amplitude (P = 0.007), and
      basal GH secretion (P = 0.03). GHRP-2 provoked a 4- to 6-fold increase in the
      mean GH concentration (P < 0.0001), the GH secretory burst amplitude (P = 0.002),
      and basal GH secretion (P = 0.0007), which were associated with a 61 +/- 13%
      increase in serum IGF-I within 24 h (P = 0.02). Compared to GHRP-2 alone, GHRH
      plus GHRP-2 elicited a further 2-fold increase in the mean GH concentration (P =
      0.04) and GH basal secretion (P = 0.02), and an additional 40 +/- 6% rise in
      serum IGF-I (P = 0.04). GHRH and GHRP-2 infusion did not alter elevated cortisol
      levels. In critically ill adults, low serum IGF-I levels were positively
      correlated with diminished pulsatile and increased basal GH secretion. Both basal
      and pulsatile GH secretion were moderately increased by continuous infusion of
      GHRH, substantially increased by GHRP-2, and strikingly increased by GHRH plus
      GHRP-2. GHRP-2 alone or combined with GHRH elicited a robust rise in circulating
      IGF-I levels within 24 h without altering serum cortisol levels. These findings
      open perspectives for GH secretagogues as potential antagonists of the catabolic
      state in critical care medicine.

PMID- 9024261
TI  - Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal
      cells.
AB  - C19 steroids are converted to estrogens by aromatase P450 (P450arom). Aromatase
      expression in humans is regulated by use of tissue-specific promoters in the
      placenta (promoter I.1), adipose tissue (promoters I.4, I.3, and II), and gonads
      (promoter II). The use of each promoter gives rise to a population of P450arom
      messenger ribonucleic acid (mRNA) species with a unique untranslated 5'-terminus.
      Aromatase is not expressed in the endometrium of disease-free women. We
      demonstrated, however, the presence of P450arom mRNA in pelvic endometriotic
      implants and eutopic endometrial curettings of women with endometriosis. In the
      current report, aromatase activity and P450arom gene expression were investigated
      in cultured stromal cells derived from eutopic endometrium and ovarian
      endometriomas of women with pelvic endometriosis. We also investigated the
      hormonal regulation of aromatase expression and alternative promoter use in these
      cells. The effects of interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-11,
      oncostatin M, IL-15, tumor necrosis factor-alpha, PGE2, estradiol, R5020,
      dexamethasone, and dibutyryl cAMP (Bt2cAMP) on aromatase activity in
      endometriosis-derived stromal cells were assessed. We chose treatments with PGs
      and ILs because of the inflammatory nature of endometriosis. PGE2 stimulated
      aromatase activity in endometriosis-derived stromal cells by 19- to 44-fold (37
      221 pmol/mg protein-4 h), whereas Bt2cAMP induction was 26- to 60-fold the
      baseline level. No stimulation was observed by estradiol or R5020 or by IL-1
      beta, IL-2, IL-6, IL-11, IL-15, or TNF alpha in the presence or absence of
      glucocorticoids. A modest induction of aromatase activity (2-fold) was observed
      in dexamethasone- plus oncostatin M-treated cells. These changes in aromatase
      activity were accompanied by comparable changes in the levels of P450arom mRNA
      levels, determined by a quantitative reverse transcription-PCR method. Promoter
      specific 5'-ends of P450arom transcripts in total RNA from endometriosis-derived
      stromal cells treated with PGE2 and Bt2cAMP were amplified employing a novel
      modified rapid amplification of cDNA5'-ends/Southern hybridization method using
      exon-specific oligonucleotide probes. The majority of P450arom transcripts in
      these cells contained the gonadal-type promoter II-specific sequences, whereas
      very few transcripts contained adipose-type promoter I.3- and I.4-specific
      sequences. PGE2 appears to be the most potent known stimulator of aromatase in
      endometriosis. Aromatase expression in PGE2-stimulated stromal cells of
      endometriosis is regulated primarily by the classically located promoter II,
      which, in turn, is regulated by cAMP. As PGE2 is known to increase intracellular
      cAMP levels, estrogen biosynthesis in endometriosis may be primarily regulated by
      PGE2 that is locally produced. Consequent local estrogen production may promote
      the growth of endometriotic implants.

PMID- 9024262
TI  - Effects of ovine corticotropin-releasing hormone injection and desmopressin
      coadministration on galanin and adrenocorticotropin plasma levels in normal
      women.
AB  - The neuropeptide galanin (GAL) has been shown to be located in the pituitary
      gland and to modulate the secretion of several pituitary hormones. In the human
      pituitary, GAL is almost exclusively located within corticotrophs. We examined
      whether GAL is secreted from corticotrophs in response to stimuli that induce
      ACTH release. Plasma levels of GAL and ACTH were evaluated in six healthy female
      subjects in the follicular phase of the menstrual cycle after the following
      treatments: 1) ovine CRH (oCRH) injection during saline (SAL) infusion, 2) oCRH
      injection during infusion of the arginine vasopressin analog desmopressin (DP),
      3) SAL injection during DP infusion, and 4) SAL injection during SAL infusion. DP
      (4.3 ng/min.kg BW) or SAL was infused from 0-60 min. oCRH (1 microgram/kg BW) or
      SAL was administered by a 2-min injection at 5 min. The expected ACTH response to
      oCRH was enhanced by the concomitant DP administration (peak level, 10.39 +/-
      1.12 vs. 21.37 +/- 3.43 pmol/L in SAL infusion plus oCRH injection vs. DP
      infusion plus oCRH injection, respectively; P < 0.05). The mean integrated ACTH
      response, expressed as the area under the curve, to SAL infusion plus oCRH
      injection vs. that to DP infusion plus oCRH injection was 288.23 +/- 61.94 vs.
      699.70 +/- 91.80 pmol/L.60 min, respectively (P < 0.05). A slight, but not
      significant, increase was observed in ACTH values after DP infusion plus SAL
      injection compared to that after SAL infusion plus SAL injection challenge.
      Plasma GAL levels were highly variable. No changes in GAL levels were found
      concomitant to ACTH values in either experimental group. In fact, GAL levels were
      not significantly affected by either treatment. These data confirm that DP
      potentiates the ACTH response to CRH in humans. Furthermore, our results suggest
      that GAL is probably not cosecreted with ACTH in normal subjects. The possibility
      exists that GAL produced by corticotrophs exerts its action principally through a
      locally mediated paracrine or autocrine mechanism without being secreted into the
      bloodstream.

PMID- 9024263
TI  - Somatic mutations of the angiotensin II (AT1) receptor gene are not present in
      aldosterone-producing adenoma.
AB  - Angiotensin II stimulates aldosterone secretion from the adrenal zona glomerulosa
      and mediates most of its biological effects via G protein-coupled type 1
      angiotensin II receptors (AT1). A number of G protein-coupled receptors are
      constitutively activated as a result of somatic mutations in the gene encoding
      the protein. It is, therefore, possible that primary hyperaldosteronism caused by
      an aldosterone-producing adenoma (APA) may be the result of constitutive
      activation of the AT1 receptor. The 1.1-kilobase coding region (exon 5) of the
      AT1 receptor gene was analyzed in APA and normal adrenal tissue for the presence
      of mutations using single stranded conformational polymorphism and sequencing
      techniques. In 17 APAs, no functional mutations were found that could account for
      the observed pathophysiology. However, three silent polymorphisms were detected
      in regions encoding the second extracellular loop, the intracellular arm
      preceding the COOH terminal, and the 3'-untranslated region. In conclusion,
      somatic mutations in the coding region of the AT1 receptor gene do not appear to
      play a role in primary hyperaldosteronism caused by an APA.

PMID- 9024264
TI  - Incomplete thyrotroph suppression determined by third generation thyrotropin
      assay in subacute thyroiditis compared to silent thyroiditis or hyperthyroid
      Graves' disease.
AB  - Serum TSH concentrations were determined by both second and third generation
      assays in three types of thyrotoxicosis associated with subacute thyroiditis,
      silent thyroiditis, and hyperthyroid Graves' disease at the time of each
      patient's initial visit to the clinic. Serum TSH concentrations as measured by
      the second generation assay with an analytical sensitivity of 0.04 mU/L were
      below the detection limit in every patient. In contrast, serum TSH concentrations
      as measured by the third generation assay with an analytical sensitivity of 0.009
      mU/L were below the detection limit in 18 of 21 (86%) patients with Graves'
      disease, 18 of 20 (90%) with silent thyroiditis, but only 4 of 18 (22%) with
      subacute thyroiditis. Changes in serum TSH concentrations were studied in healthy
      volunteers given daily 75 micrograms of T3; their serum TSH concentrations on the
      second generation assay fell below the detection limit within 3 days in every
      subject. However, the TSH concentration measured by the third generation assay
      remained above the detection limit in 6 of 8 normal subjects even on the 14th day
      of therapy. The reason for incomplete TSH suppression in most subacute
      thyroiditis patients may be that these patients had notable neck pain, and their
      initial visit to the clinic may have occurred earlier after the onset of disease
      than with patients who have had silent thyroiditis or Graves' disease. Thus, the
      serum TSH concentration had not decreased sufficiently below the detection limit
      at the time blood was drawn. The data suggest also that the highly sensitive TSH
      assay, if the level is above the detection limit, can be used to suppose that the
      short duration of the initiation of thyrotoxicosis indicates a case of subacute
      thyroiditis.

PMID- 9024265
TI  - A randomized controlled trial to compare the efficacy of cyclical parathyroid
      hormone versus cyclical parathyroid hormone and sequential calcitonin to improve
      bone mass in postmenopausal women with osteoporosis.
AB  - Short cycles of human (h) PTH-(1-34) may have an anabolic effect to increase bone
      mass in patients with osteoporosis. As PTH also stimulates bone resorption, it is
      theoretically possible to enhance the anabolic effects of PTH by using a
      sequential antiresorptive agent in the treatment cycle. To test this hypothesis,
      30 women with osteoporosis, aged 67 +/- 8 yr, completed a 2-yr protocol that
      comprised 28-day courses of hPTH-(1-34) (800 U) given by daily sc injections;
      each course was repeated at 3-month intervals. By random allocation, patients
      either received sequential calcitonin (CT) immediately following the cycle of
      hPTH-(1-34) (75 U/day, sc; PTH + CT; n = 16) or placebo CT (PTH alone; n = 14)
      for 42 days. Baseline bone mineral density (BMD) at the lumbar spine site
      revealed t scores of -3.7 +/- 1.2 (+/-SD) for the PTH alone group and -3.0 +/-
      1.4 for the PTH + CT groups, who had 2.0 +/- 2.3 and 1.8 +/- 2.4 vertebral
      fractures, respectively, at entry to the study. At the end of the 2 yr, the
      lumbar spine BMD increased from 0.720 +/- 0.130 to 0.793 +/- 0.177 g/cm2 (10.2%)
      in the PTH group and from 0.760 +/- 0.168 to 0.820 +/- 0.149 g/cm2 (7.9%) in the
      PTH + CT group. These changes were significant over time in both groups (P <
      0.001). Although the final 2-yr lumbar spine BMD was not significantly different
      between the two treatment groups, those patients receiving sequential CT
      injections gained bone mass at a consistently slower rate. Changes in BMD at the
      femoral neck averaged +2.4% and -1.8% in the PTH and PTH + CT groups,
      respectively, neither of which was significant. In the group receiving only
      cyclical hPTH-(1-34), the observed 2-yr vertebral fracture incidence was 4.5
      compared to 23.0/100 patient yr in the PTH + CT group (P = 0.078). During the
      first two cycles, changes in biochemical markers of bone formation (serum total
      alkaline phosphatase, bone-specific alkaline phosphatase, and osteocalcin) and
      bone resorption (fasting urinary hydroxyproline and N-telopeptide excretion) were
      significantly increased over pretreatment values after 28 days of hPTH-(1-34)
      injections (P < 0.05 to P < 0.01 for both groups). Even end of cycle values
      remained elevated over the study baseline across time (P < 0.01). There were no
      significant differences for any outcome parameter between the two treatment
      groups. We conclude that short cycles (28 days) of daily hPTH-(1-34) injections
      result in significant increases in lumbar spine BMD, without significant changes
      in cortical bone mass at the femoral neck. Very low incident vertebral fracture
      rates were documented over 2 yr. However, there is no evidence that sequential
      antiresorptive therapy with CT is of any benefit over that conferred by cyclical
      PTH alone.

PMID- 9024266
TI  - Two-year treatment of growth hormone (GH) receptor deficiency with recombinant
      insulin-like growth factor I in 22 children: comparison of two dosage levels and
      to GH-treated GH deficiency.
AB  - We have reported 1-yr results of a double blind, placebo-controlled trial of
      recombinant human insulin-like growth factor I (rhIGF-I) replacement in 16
      children from the Ecuadorian GH receptor-deficient (GHRD) population. This report
      extends observations of rhIGF-I efficacy at two dosage levels [120 micrograms/kg
      BW twice daily (n = 15) and 80 micrograms/kg twice daily (n = 7)] over 2 yr,
      compares biochemical responses [serum IGF-I and IGF-binding protein-3 (IGFBP-3)]
      and their relationship to growth effects, and compares treatment effects of rhIGF
      I in GHRD to rhGH in idiopathic GH deficiency (GHD). There were no baseline
      differences between the low and high dose groups for growth velocity (GV), bone
      age (BA), SD score for height, or percent mean body weight for height (MBWH).
      Over 2 yr of rhIGF-I treatment, there were no differences in GV or in changes in
      height SD score, height age (HA), or BA between the two groups; a subgroup of six
      subjects at the higher dose followed for a third year continued at the second
      year GV. The higher dose resulted in a greater change in percent MBWH. GV in yr 1
      and 2 for the entire group and in yr 3 for a subgroup were greater for GH-treated
      GHD (n = 11). The GHD group showed a greater change in SD score for height and
      HA, but did not differ from the rhIGF-I-treated GHRD group in the change in BA
      (delta BA) or delta HA/delta BA over 2 yr. There was a greater change in percent
      MBWH in GHRD. There were no differences between dosage groups for serum IGF-I
      levels at baseline or the near-normal trough levels 12 h after rhIGF-I injection;
      these individual levels correlated with HA gain in yr 1 and 2. IGFBP-3 levels
      were markedly low, with no changes of significance with treatment. Comparable
      growth responses to the two dosage levels and the biochemical changes indicate a
      plateau effect at or below 80 micrograms/kg BW twice daily. The growth response
      and favorable trough levels of IGF-I despite the overall lack of increase in
      circulating IGFBP-3 levels suggest an alternative mechanism for sustaining IGF-I
      levels and avoiding rapid clearance of rhIGF-I. The greater increase in MBWH with
      treatment of GHRD than with treatment of GHD may reflect comparable effects on
      lean body mass without the lipolytic effects of GH in the GHRD subjects. The
      difference in growth response between rhIGF-I-treated GHRD and rhGH-treated GHD
      groups is consistent with the hypothesis that 20% or more of GH-influenced growth
      is due to the direct effects of GH on bone. Nonetheless, the comparable delta
      HA/delta BA suggests similar long term effects of replacement therapy in the two
      conditions.

PMID- 9024267
TI  - Suppression of growth hormone (GH) hypersecretion due to ectopic GH-releasing
      hormone (GHRH) by a selective GHRH antagonist.
AB  - We have recently demonstrated that a competitive antagonist of GHRH, (N-Ac-Tyr1,D
      Arg2)GHRH-(1-29)NH2 (GHRH-Ant), eliminates nearly all nocturnal GH pulsatility in
      normal subjects, supporting the hypothesis that GH pulsatility is driven by GHRH.
      In this study, we compared the effects of every 12 h i.v. boluses of either GHRH
      Ant or saline on 24-h GH profiles in a patient with acromegaly due to a
      metastatic GHRH-secreting carcinoid tumor. Bolus doses of GHRH-Ant (400
      micrograms/kg, i.v.) acutely suppressed GH concentration to 30-40% of the
      pretreatment baseline, and this effect lasted 3-4 h. Administration of GHRH (0.33
      microgram/kg, i.v.) bolus resulted in a small rise in GH, and this effect was
      blocked by GHRH-Ant (400 micrograms/kg). During saline treatment, the secretory
      patterns of both GH and ectopic GHRH were pulsatile; however, there was no
      correlation between changes in plasma GHRH and GH concentrations. This lack of
      correlation was probably due to the majority of circulating GHRH immunoreactivity
      consisting of nonbiologically active GHRH fragments. These data support the
      hypothesis that GH hypersecretion in the ectopic GHRH syndrome requires GHRH
      receptor occupancy and validates the use of GHRH-Ant to probe the potential
      involvement of endogenous GHRH in patients with acromegaly due to pituitary
      somatotropinoma.

PMID- 9024268
TI  - Estrogen replacement therapy decreases hyperandrogenicity and improves glucose
      homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent
      diabetes mellitus.
AB  - Hyperandrogenicity in women is closely associated with insulin resistance and a
      risk factor for cardiovascular disease and noninsulin-dependent diabetes mellitus
      (NIDDM). Therefore, 25 postmenopausal women with NIDDM and sex hormone-binding
      globulin values less than 60 nmol/L, as an indicator of a moderate
      hyperandrogenicity, were treated with 2 mg 17-beta-estradiol orally for 3 months
      in a double-blind, cross-over, placebo-controlled trial. During the last 16 days
      of active treatment, 1 mg norethisterone acetate was added for 10 days for
      endometrial protection. Blood glucose, glycosylated hemoglobin, insulin, c
      peptide, lipoprotein profile, sex steroid hormones, GH, and insulin-like growth
      factor I (IGF-I) were measured, and insulin sensitivity was determined by the
      euglycemic hyperinsulinemic clamp method. All metabolic measurements were taken
      at baseline and after 68 days of active or placebo treatment. Estradiol
      treatment, compared with the placebo period, was followed by a marked increase of
      sex hormone-binding globulin and a decrease of free testosterone. Blood glucose,
      glycosylated hemoglobin, c-peptide, total cholesterol, low-density lipoprotein
      cholesterol, and IGF-I decreased significantly (P < 0.01-P < 0.001), whereas high
      density lipoprotein cholesterol rose (P < 0.001). In conclusion, estrogen
      replacement therapy in postmenopausal women with NIDDM ameliorated
      hyperandrogenicity, and this was accompanied by marked improvements in glucose
      homeostasis and lipoprotein profile.

PMID- 9024269
TI  - The impact of insulin secretion on the ovarian response to exogenous
      gonadotropins in polycystic ovary syndrome.
AB  - The aim of the study was to evaluate the influence of insulin level on the
      ovarian response to FSH when inducing ovulation in patients affected by
      polycystic ovarian syndrome (PCOS). To evaluate the presence of hyperinsulinemia,
      34 patients affected by PCOS were studied by an oral glucose tolerance test, then
      patients were stimulated for 52 cycles using FSH to induce ovulation. The ovarian
      response to therapy was evaluated by ultrasounds and as estradiol (E2) and
      androstenedione (A) plasma level determinations. On the basis of the insulinemic
      response to the glucose challenge, 20 patients were considered to be
      hyperinsulinemic and 14 normoinsulinemic. The hormonal features of each group
      were similar. The ovulation rate was similar in hyperinsulinemic and
      normoinsulinemic subjects, whereas the incidence of ovarian hyperstimulation was
      significantly higher in the hyperinsulinemic group. The increase in ovarian
      dimensions observed in hyperinsulinemic subjects after gonadotropin stimulation
      was more marked than that observed in normoinsulinemic ones. This was caused by
      the development of a larger number of immature follicles. E2 levels gradually
      increased after gonadotropin stimulation in both groups of subjects; however,
      higher levels were observed in hyperinsulinemic patients. During stimulation, the
      higher E2/A ratio suggests the presence of a greater aromatization activity in
      hyper-insulinemic patients. In conclusion, the present study suggests that, in
      PCOS, the insulinemic pattern may influence the ovarian response to gonadotropin
      administration; thus, hyperinsulinemic subjects may be at greater risk of ovarian
      hyperstimulation syndrome than normoinsulinemic subjects.

PMID- 9024270
TI  - Molecular analysis of mutated thyroid peroxidase detected in patients with total
      iodide organification defects.
AB  - Wild-type and mutant thyroid peroxidase (TPO) was expressed in a Semliki Forest
      Virus (SFV)-based transient expression system in Chinese hamster ovary-K1 cells.
      Twenty four hours after transfection proteins immunoreactive with TPO antibodies
      could be detected on a Western blot. Peroxidase activity was assayed using both
      the guaiacol and the I3- assay. Addition of hematin was necessary to obtain
      enzymatic active TPO. Thyroid peroxidase complementary DNA constructs containing
      mutations originally found in patients with hereditary congenital hypothyroidism
      caused by total iodide organification defects were analyzed using these
      techniques. In all cases TPO was expressed as shown by Western blotting and
      immunostaining. Enzymatic activity (measured by guaiacol and iodide oxidation
      assay) was below the detection level in four out of five mutants. The only mutant
      yielding TPO with enzymatic activity was G 1858 A (Gly 590 Ser). However, the
      mutation could affect splicing of TPO messenger RNA, leading to inactive TPO,
      because it is located at the exon 10/intron 10 border.

PMID- 9024271
TI  - UKPDS 20: plasma leptin, obesity, and plasma insulin in type 2 diabetic subjects.
AB  - We measured plasma leptin and insulin concentrations across a spectrum of obesity
      in 829 white Caucasian, 154 Afro-Caribbean, and 204 Asian type 2 diabetic
      subjects. Although the leptin concentrations covered a large range, there were no
      subgroups of diabetic subjects with very high or low leptin levels that would
      suggest mutations in the leptin gene or leptin receptor gene comparable to the
      obese diabetic ob/ob and db/db mice models respectively. In all three ethnic
      groups, leptin concentrations correlated with body mass index (BMI) in a similar
      manner to nondiabetic patients and were higher in females than males after
      adjustment for BMI, with no difference between ethnic groups. In a multivariate
      regression analysis, plasma leptin was associated with gender and BMI, (both P <
      1 x 10(-17)) and with fasting plasma insulin concentrations (P = 5 x 10(-9)).
      Subjects treated with insulin had both raised insulin and leptin concentrations.
      When matched for different therapies, gender, and BMI, diabetic subjects with
      high leptin levels also had high insulin levels (P < 0.0009). High leptin
      concentrations may in part be influenced by hyperinsulinemia or impaired insulin
      sensitivity.

PMID- 9024272
TI  - Treatment of isolated hypogonadotropic hypogonadism effect on bone mineral
      density and bone turnover.
AB  - Isolated hypogonadotropic hypogonadism (IHH) presents with delayed puberty in the
      late teens or early twenties, with a period of testosterone deficiency during
      active growth. The aims of the study were to determine 1) whether long term
      treatment of IHH results in normalization of bone density (BMD) and bone
      turnover, and 2) whether BMD and bone turnover respond to increasing doses of
      hCG. We studied 10 men, aged 26-46 yr, with IHH who were treated with hCG or
      testosterone esters (Sustanon) for 2-22 yr, with age at the start of treatment
      between 17-29 yr, and 10 age- and body weight-matched normal men as a control
      group. At baseline, lumbar spine, femoral neck, trochanter, and Ward's triangle
      BMD values were decreased, and serum bone Gla-protein, bone alkaline phosphatase,
      and urinary pyridinoline, deoxypyridinoline, and N-terminal telopeptide of type I
      collagen were increased compared with control values (by paired t test, P = 0.02,
      0.03, 0.01, 0.05, 0.002, 0.02, 0.02, 0.007, and 0.006, respectively). The age at
      initial therapy was significantly correlated with total body BMD (r = -0.73; P =
      0.017) and lumbar spine BMD (r = -0.756; P = 0.0097). Serum free testosterone was
      correlated with total body and trochanter BMD (r = 0.635; P = 0.048 and r =
      0.629; P = 0.05), and serum free estradiol was correlated with total body and
      trochanter BMD (r = 0.641; P = 0.045 and r = 0.634; P = 0.048). Six of the 10
      patients were recruited for a longitudinal study in which the dose of hCG was
      increased monthly from 2000 i.u. twice per week to 6000 i.u. twice per week.
      After increasing doses of hCG, levels of serum testosterone and estradiol and
      total body BMD increased significantly (by paired t test P = 0.001, 0.003, and
      0.01, respectively). Serum bone Gla-protein levels increased by the first month
      and then decreased (paired t test, corrected by Bonferroni's method). Serum bone
      alkaline phosphatase and urinary N-terminal telopeptide of type I
      collagen/creatinine levels decreased significantly after increasing the dose of
      hCG. We conclude that patients with IHH who have serum testosterone within the
      laboratory reference range may require a higher dose of hCG to normalize BMD and
      bone turnover.

PMID- 9024273
TI  - Detection of IL-12, IL-13, and IL-15 messenger ribonucleic acid in the thyroid of
      patients with autoimmune thyroid disease.
AB  - IL-12, IL-13, and IL-15 are important cytokines that have not been studied
      previously in human autoimmune thyroid diseases. By applying RT-PCR on RNA
      extracted from tissue samples, we have investigated in vivo gene expression of
      these cytokines in multinodular goiter (MNG), Graves' disease (GD), and
      Hashimoto's thyroiditis (HT). In addition, in vitro studies were carried out
      using the transformed human thyroid cell line, HT-ori3, and primary thyroid cell
      cultures derived from patients with GD. These cells were used either unstimulated
      or stimulated for 12 h with TSH, IL-1, or interferon-gamma (IFN-gamma). IL-12 p40
      gene expression was identified in 2 of 10 MNG samples, 6 of 12 GD, and 3 of 4 HT.
      HT-ori3 and primary thyroid cell cultures were positive for IL-12 p40 messenger
      RNA (mRNA) expression in both unstimulated and stimulated cell cultures. IL-13
      mRNA was expressed in 2 MNG, 9 GD, and 1 HT sample. Both HT-ori3 and primary
      thyroid cultures expressed IL-13 after TSH, IL-1, or IFN-gamma stimulation;
      unstimulated primary cultures of thyroid cells, however, did not express IL-13.
      IL-15 gene expression was detected in 8 MNG, 8 GD, and 4 HT samples. HT-ori3 and
      primary thyroid cell cultures, stimulated with TSH, IL-1, or IFN-gamma, showed
      expression of this cytokine. Unstimulated cells showed only a weak expression.
      Our results indicate that the cytokine patterns in the various diseases studied
      are heterogeneous; that thyroid cells can express IL-12, IL-13, and IL-15 mRNA in
      culture, particularly after TSH, IL-1, or IFN-gamma stimulation; and that IL-15
      is expressed in most of the tissue samples studied.

PMID- 9024274
TI  - Cyclooxygenase-dependent thyroid cell proliferation induced by immunoglobulins
      from patients with Graves' disease.
AB  - IgG associated with Graves' disease bind to the TSH receptor and alter thyroid
      growth and function, mainly through the stimulation of adenylyl cyclase. In
      addition, Graves' IgG are able to interact with the phospholipase C (PLC)/Ca2+
      and phospholipase A2 (PLA2)/arachidonic acid (AA) cascades. The activation of
      this latter pathway leads to thyroid cell growth in vitro. The elucidation of
      additional mechanisms of action of Graves' IgG has made possible the
      identification of four subgroups of patients, characterized by IgG with different
      biochemical activities (extent of cAMP and AA release stimulation in in vitro
      assays). On the basis of these results, a novel therapeutic approach could be
      proposed based on the inhibition of PLA2 and AA metabolism. To test this
      hypothesis, the ability of IgG from 56 Graves' patients to stimulate
      [3H]thymidine incorporation in FRTL5 thyroid cells in the presence and absence of
      the cyclooxygenase inhibitor indomethacin (2.5 x 10(-6) mol/L) was measured. A
      significant reduction in [3H]thymidine incorporation was found (33% inhibition; P
      < 0.0001) upon pretreatment with indomethacin, suggesting that in vitro thyroid
      cell growth is regulated by cyclooxygenase metabolites. This strengthens the
      argument for involvement of the PLA2/AA cascade in the pathophysiology of Graves'
      disease and the proposal for novel selective pharmacological treatments of these
      patients.

PMID- 9024275
TI  - Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical
      characterization of a novel renal phosphate-wasting disorder.
AB  - Renal phosphate-wasting disorders are the most common form of hereditary rickets
      and osteomalacia in western countries. Although autosomal dominant transmission
      of renal phosphate wasting has been described, previous studies included too few
      affected individuals to adequately characterize the disorder. We performed
      clinical and biochemical evaluations of individuals from a large kindred with
      autosomal dominant hypophosphatemic rickets/osteomalacia. We identified 23
      affected members in this family, and for some individuals, follow-up was up to 25
      yr. As patients were all members of the same kindred, we had the opportunity to
      determine the clinical manifestations of the disorder in patients who presumably
      all have the same genetic mutation. Affected individuals have isolated renal
      phosphate wasting and inappropriately normal serum calcitriol concentrations. The
      inheritance pattern was consistent with autosomal dominant transmission with
      variable penetrance. The family contained two subgroups of affected individuals.
      Group 1 consisted of patients who presented with renal phosphate wasting as
      adolescents or adults. These patients presented with bone pain, weakness, and
      insufficiency fractures, but did not manifest lower extremity deformity. Group 2
      consisted of patients who presented with phosphate wasting, rickets, and lower
      extremity deformity as children. Surprisingly, some individuals in group 2 lost
      the renal phosphate-wasting defect after puberty. In conclusion, autosomal
      dominant hypophosphatemic rickets/osteomalacia is an inherited disorder of
      isolated renal phosphate wasting. The spectrum of disease includes delayed onset
      of penetrance and loss of the renal phosphate-wasting defect. Our results have
      implications in the evaluation of patients who present with renal phosphate
      wasting as either adults or children.

PMID- 9024276
TI  - Association between plasma total testosterone and cardiovascular risk factors in
      healthy adult men: The Telecom Study.
AB  - The associations between androgens and cardiovascular risk factors in men are
      controversial. A nested case-control study was used to compare the levels of
      cardiovascular risk factors in two groups (n = 25 each) of healthy men contrasted
      by their plasma total testosterone (PTT) concentration, matched by age and ethnic
      origin. Compared to the men with normal PTT (mean +/- SEM, 19.8 +/- 0.7 nmol/L),
      the men with low PTT (10.1 +/- 0.3 nmol/L) had a significantly higher body mass
      index (P < 0.01), waist/hip ratio (P < 0.001), systolic blood pressure (P <
      0.05), fasting and 2-h plasma glucose (P < 0.04 and P < 0.02 respectively), serum
      triglycerides (P < 0.001), total cholesterol (P < 0.04), low density lipoprotein
      cholesterol (P < 0.01), apolipoprotein B (P < 0.01), fasting and 2-h plasma
      insulin (both P < 0.0001), and lower values of serum high density lipoprotein
      cholesterol (P < 0.01) and apolipoprotein AI (P < 0.05). After adjustment for
      both body mass index and waist/hip ratio, fasting and 2-h plasma insulin and
      triglyceride levels remained significantly different between the two groups (P <
      0.04, P < 0.001, and P < 0.03 respectively). Plasma sex hormone-binding globulin
      was markedly decreased in the low PTT group (P < 0.0001), whereas bioavailable
      testosterone was not significantly different. This case-control study provides
      further and stronger evidence of a negative association between PTT and plasma
      insulin in men, as suggested by cross-sectional studies. Because these are
      observational data, neither causality nor the direction of the associations among
      PTT, sex hormone-binding globulin, and insulin sensitivity can be determined.
      Intervention studies are needed to better assess the metabolic and cardiovascular
      benefits of androgen treatment that have been suggested by preliminary clinical
      trials.

PMID- 9024277
TI  - Autosomal recessive nephrogenic diabetes insipidus caused by an aquaporin-2
      mutation.
AB  - Vasopressin V2 receptors, expressed from an x-chromosomal gene, are involved in
      antidiuresis, but also in release of coagulation factor VIII and von Willebrand
      factor (vWF). The present study describes autosomal recessive nephrogenic
      diabetes insipidus (NDI) in a large cluster of patients in Israel's Lower
      Galilee. Evidence for an intact V2 receptor was concluded by their normal
      increase in factor VIII and vWF after desmopressin infusion. Thus, in these
      patients a defect in the pathway beyond the V2 receptor was suspected. The recent
      cloning of the human Aquaporin-2 gene enabled us to test this gene as a candidate
      for such a postreceptor defect. Direct sequencing of the Aquaporin-2 gene
      revealed a G298T substitution causing a Gly100Stop nonsense mutation in the third
      transmembrane region. Because this putative disease-causing mutation was
      identified in index patients of different families, we suggest that all patients
      are descendants of a common ancestor. Thus, this new entity is characterized by
      an autosomal recessive NDI. The differential response of clotting factors and
      urine osmolality to desmopressin may provide a simple tool for clinical diagnosis
      of a V2-postreceptor defect. The early stop-codon of Aquaporin-2 results in
      complete resistance to vasopressin antidiuretic effect.

PMID- 9024278
TI  - Somatostatin and growth hormone-releasing hormone in normal and tumoral human
      breast tissue: endogenous content, in vitro pulsatile release, and regulation.
AB  - Endogenous production of SRIH and GHRH was analyzed in human breast tissue. SRIH
      precursor (pro-SRIH) was identified after Sephadex G-50 filtration of acetic acid
      extracts of normal and tumoral human breast samples. SRIH-(1-14) or -(1-28) could
      not be detected in breast tissue, whereas the immunoreactive SRIH released in
      vitro was characterized as SRIH-(1-28). Endogenous production of GHRH was
      assessed by identification of GHRH messenger ribonucleic acid by PCR followed by
      sequencing of the amplified complementary DNA and by high performance liquid
      chromatographic characterization of immunoreactive GHRH contained in the tissue
      and released in vitro. There were no differences in pro-SRIH or GHRH-(1-44)
      tissue contents between normal and tumoral samples. The release of both peptides
      was evidenced in perifusion and static incubation. Perifusion of normal breast
      tissue (n = 3) showed pulsatile release of SRIH and GHRH. Perifusion of tumors (n
      = 4) showed SRIH release in 50% of the cases. SRIH release was pulsatile in one
      case. GHRH release was observed in the four tumoral samples analyzed, but was
      pulsatile in only one case. In static incubation, tumors (n = 6) secreted 13
      times more GHRH than did normal samples (n = 3; 383 +/- 92 vs. 29.6 +/- 4.6
      fmol/mg protein; P < 0.05). Stimulation of GHRH release by exogenous SRIH was
      observed only with the normal tissue. Together these data provide evidence for
      the existence of local production of SRIH and GHRH by human breast.
      Hypersecretion of GHRH by breast tumors indicates that this peptide could play a
      role in maintaining epithelial cell proliferation as is the case for other
      peptides produced locally.

PMID- 9024279
TI  - The short-term infusion of ovine corticotropin-releasing hormone does not alter
      luteinizing hormone concentrations in young adult men.
AB  - Chronic stress leads to suppression of the hypothalamic-pituitary-gonadal (HPG)
      axis with decreased plasma LH concentrations. This is believed to be due to the
      influence of elevated levels of endogenous CRH mediated via the endogenous opiate
      peptide receptor. Efforts to reproduce this phenomenon with exogenous CRH have
      produced varied results depending on the dose and route of administration of CRH
      as well as on the species, gonadal state, and endogenous opiate peptide system
      tone of the experimental subjects. In humans, conflicting results for CRH-induced
      suppression of the HPG axis exist for women, and the issue has not been addressed
      sufficiently in men. We, therefore, studied the effects of a 4-h infusion of
      ovine CRH (oCRH) on LH secretion in 11 healthy, nonobese young adult men (age
      range, 20-33 yr). Subjects were admitted to the General Clinical Research Center
      on 4 occasions in randomized order. They underwent blood sampling for LH at 10
      min intervals from 1800-0600 h. From 2200-0200 h, subjects received one of the
      following iv infusion protocols in blinded fashion: a normal saline (NS) bolus
      and NS infusion, a naloxone (NAL) bolus (4 mg) and NAL infusion (2 mg/h), a NS
      bolus and oCRH infusion (1 microgram/kg.h; maximum, 75 micrograms/h), and a NAL
      bolus and both NAL and oCRH infusions, using the above-mentioned doses. For each
      time point, serum LH values from the four experimental conditions were compared
      by one-way ANOVA with repeated measures; the paired t test was applied post-hoc.
      This experimental model is predicted to have a beta-error of less than 0.10 for
      identifying a 1.0 U/L change in LH levels. As expected, NAL was associated with a
      transient, but significant, rise in serum LH concentrations compared to those in
      the NS control. On the other hand, oCRH administration did not result in any
      significant alteration in either basal or NAL-stimulated LH levels. We conclude
      that exogenous oCRH administration does not significantly alter pituitary
      secretion of LH in healthy men. We speculate that any suppressive effect of CRH
      on the HPG axis occurs at the level of the hypothalamus.

PMID- 9024280
TI  - Analysis of the SRY gene in gonadal tissue of subjects with 46,XY gonadal
      dysgenesis.

PMID- 9024281
TI  - "Add-back" estrogen reverses cognitive deficits induced by a gonadotropin
      releasing hormone agonist in women with leiomyomata uteri.

PMID- 9024282
TI  - Unusual changes in parathyroid glands in patients with chronic renal failure.

PMID- 9024283
TI  - High-dose transdermal estrogen, corticotropin-releasing hormone, and postnatal
      depression.

PMID- 9024284
TI  - Learning from the mistakes of Malthus: GI and manpower planning.

PMID- 9024285
TI  - Image of the month. Spur cell anemia.

PMID- 9024286
TI  - Clinical and molecular features of the hereditary mixed polyposis syndrome.
AB  - BACKGROUND & AIMS: Various inherited syndromes predispose to the development of
      colonic juvenile polyps and colorectal cancer, with potential importance for
      sporadic tumorigenesis. This study describes features of a possibly new syndrome
      of atypical juvenile polyps and other colonic tumors and compares these features
      with those of known gastrointestinal tumor syndromes. METHODS: A large family,
      St. Mark's family 96, with a tendency to develop colonic polyps of mixed
      histological types is described. Genetic linkage to known polyposis syndromes has
      been tested. RESULTS: Adenomatous and hyperplastic polyps occur in affected
      members of the family, although the characteristic lesion is an atypical juvenile
      polyp. Some affected individuals have developed polyps of more than one type, and
      individual polyps may contain features of more than one histological type. Polyps
      can undergo malignant change. Typically, fewer than 15 polyps are found at
      colonoscopy and there is no extracolonic disease associated with the development
      of polyps. The family's polyps seem to be inherited in an autosomal-dominant
      fashion, but the disease is probably unlinked to candidate loci with importance
      in colorectal tumorigenesis, such as APC, hMSH2, and hMLH1. CONCLUSIONS: We term
      this family's disease hereditary mixed polyposis syndrome (HMPS). Although
      mutations in the putative HMPS gene may be responsible for syndromes such as
      juvenile and Peutz-Jeghers polyposes, HMPS may also be a distinct disease.

PMID- 9024287
TI  - Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of
      its effect on clinical management.
AB  - BACKGROUND & AIMS: Recently [111In-DTPA-D-Phe1]-octreotide was approved for
      somatostatin receptor scintigraphy (SRS) of gastroenteropancreatic tumors. SRS
      and other tumor localization methods can be time consuming, expensive, and
      involve patient inconvenience. The role of SRS in comparison to other tumor
      localization modalities remains undefined because the relative effects of these
      methods on management have not been studied. The aim of this study was to
      determine whether SRS alters clinical management in Zollinger-Ellison syndrome.
      METHODS: One hundred twenty-two consecutive patients were studied prospectively.
      Each patient was assigned to one of five different clinical categories.
      Conventional imaging studies (ultrasonography, computerized tomography, magnetic
      resonance image, angiography, and bone scan) were performed, and the management
      was proposed. SRS was then performed. Clinical management was reassessed, and
      whether SRS altered management was determined based on six criteria. RESULTS: SRS
      was superior to any single imaging study. SRS altered management in 47% overall
      and in 22%-60% of patients in the five different clinical categories. Primary
      tumor localization and clarification of equivocal localization results from
      conventional studies were the principal reasons for altering management. SRS was
      equally useful in patients with or without metastatic liver disease. CONCLUSIONS:
      Because of the ability of SRS to alter clinical management combined with its
      superior sensitivity, high specificity, simplicity, and cost-effectiveness, SRS
      should be the initial imaging modality for patients with gastrinomas.

PMID- 9024288
TI  - Src activation in malignant and premalignant epithelia of Barrett's esophagus.
AB  - BACKGROUND & AIMS: The neoplastic progression of Barrett's esophagus (BE) may
      involve genomic instability, inactivation of tumor suppressor genes, or
      activation of oncogenes. Because activation of Src tyrosine kinase occurs in
      malignant and premalignant epithelia of the colon, the aim of this study was to
      determine whether BE is associated with changes in Src expression and activity.
      METHODS: Src expression and in vitro protein-tyrosine kinase activity in
      endoscopic tissue samples of BE and esophageal adenocarcinoma were measured and
      compared with expression and activity in normal esophagus and duodenum from the
      same patient. Src phosphorylation was assessed by immunoblotting using
      antiphosphotyrosine antibodies and two-dimensional tryptic phosphopeptide
      mapping. RESULTS: Src-specific activity was 3-4 fold higher in BE and 6-fold
      higher in esophageal adenocarcinoma than in control tissues. Different regions of
      BE from the same patient showed heterogeneity in Src activity compared with the
      uniform Src activity observed in different regions of normal esophagus and
      duodenum. In all tissues, Src kinase activity and protein were associated
      preferentially with the Triton X-100-soluble rather than-insoluble fraction.
      Immunoblotting and two-dimensional tryptic phosphopeptide mapping showed
      dephosphorylation of Src at Tyr527 in BE. CONCLUSIONS: Src is activated in BE, in
      part, because of dephosphorylation of Tyr527. Src activation and its
      heterogeneous expression occur before development of dysplasia or carcinoma in
      BE.

PMID- 9024289
TI  - Effect of cholinergic agonists on gastrin release from primary cultures of human
      antral G cells.
AB  - BACKGROUND & AIMS: There is conflicting evidence concerning whether muscarinic
      regulation of gastrin release in humans is a direct or indirect effect on antral
      G cells. The present experiments were designed to resolve this question using an
      isolated human G-cell preparation. METHODS: The ability of muscarinic agonists to
      stimulate or inhibit gastrin release was assessed with or without an
      immunoneutralizing somatostatin antibody or an m3 receptor antagonist. The effect
      of secretogogues on G and D cells was monitored by intracellular calcium imaging.
      RESULTS: Muscarinic agonists failed to stimulate gastrin release, even after the
      removal of somatostatin-induced inhibition. Our group has previously shown that
      muscarinic agonists stimulated somatostatin release from antral D cells.
      Methacholine (100 mumol/L) increased intracellular calcium levels in cocultured D
      cells; this increase was inhibited by the m3 receptor antagonist 4
      diphenylacetoxy-n-methylpiperidine methiodide. Gastrin cells in the same field of
      view lacked a response to methacholine but showed a clear response to 10 nmol/L
      bombesin. CONCLUSIONS: The experiments indicate that vagal control of gastrin
      release in humans is indirect; stimulation would be achieved by the activation of
      intrinsic gastrin-releasing peptide neurons, and inhibition would be via the
      paracrine action of somatostatin released from adjacent D cells.

PMID- 9024290
TI  - Functional impairment of rat enterochromaffin-like cells by interleukin 1 beta.
AB  - BACKGROUND & AIMS: Histamine-producing enterochromaffin-like (ECL) cells play an
      integrative role in the regulation of acid secretion. Decreased mucosal histamine
      concentrations and increased levels of interleukin (IL) 1 beta, IL-6, and IL-8
      have been detected in the gastric mucosa inflamed with Helicobacter pylori. The
      aim of this study was to investigate the response of isolated ECL cells to these
      cytokines. METHODS: Enriched rat gastric ECL cells (85%-95%) were cultured for 2
      4 days. RESULTS: Polymerase chain reaction showed IL-1 and IL-6, but not IL-8
      receptors, in ECL cell complementary DNA. Positive receptor staining with
      biotinylated IL-1 beta corresponded to ECL cell enrichment (92%). IL-6 and IL-8
      had no effect on histamine secretion. IL-1 beta (2 U/mL) stimulated basal
      histamine secretion and nitric oxide production within 60 minutes and cyclic
      guanosine monophosphate production within 20 minutes. Pretreatment for 20 minutes
      with IL-1 beta (2 U/mL) attenuated gastrin-stimulated histamine secretion by 40%
      50%, reversed by the IL-1 receptor antagonist (10 U/ mL). Pretreatment for 20
      minutes with IL-1 beta (2 U/mL) completely inhibited gastrin-stimulated (1
      nmol/L) histidine decarboxylase activity. IL-1 beta (2 U/mL, 60 minutes)
      increased lactate dehydrogenase release to 25% of cell content. Cells pretreated
      with IL-1 beta did not respond to gastrin after a further 48-hour culture and
      showed decreased histamine content. CONCLUSIONS: ECL cells appear to express IL-1
      receptors. IL-1 beta causes sustained functional impairment of ECL cells in
      vitro.

PMID- 9024291
TI  - Rat intestinal alkaline phosphatase II messenger RNA is present in duodenal crypt
      and villus cells.
AB  - BACKGROUND & AIMS: Rats produce two messenger RNA (mRNA) isoforms encoding
      intestinal alkaline phosphatase that are regulated differentially by fat feeding
      but whose tissue distribution is not known. The aim of this study was to examine
      the distribution of these isoforms along the crypt/villus axis during fat
      feeding. METHODS: Nucleotide probes and polyclonal antibodies unique for each
      isoform were used for in situ hybridization and immunocytochemistry. RESULTS:
      mRNAs encoding isoforms I and II were distributed along the entire villus. The
      mRNA content of isoform II was more abundant. Quantitative grain counts showed
      that mRNA abundance of each isoform in the upper third of the villus was
      significantly (40%-65%) lower than in the remaining villus in the fasting
      duodenum. After fat feeding, the mRNA content of both isoforms increased over the
      villus. Five hours after feeding, the content of the mRNA encoding only isoform
      II was increased in the upper third of the villus relative to the rest of the
      villus. Only the mRNA encoding isoform II was found in the crypt cells. However,
      no immunoreactive enzyme was present in the crypt cells. CONCLUSIONS: The spatial
      expression of the two rat intestinal alkaline phosphatase isoforms is regulated
      differently in response to fat feeding.

PMID- 9024293
TI  - Carbonic anhydrase IX, MN/CA IX: analysis of stomach complementary DNA sequence
      and expression in human and rat alimentary tracts.
AB  - BACKGROUND & AIMS: CA IX (formerly MN protein) is a carbonic anhydrase isoenzyme
      whose expression is associated with human tumors. However, it has also been found
      in normal gastric mucosa. The aim of this study was to determine differences in
      complementary DNAs (cDNAs), to obtain an overview of distribution in the
      alimentary tract, and to obtain data on expression in tumors. METHODS: A CA9 cDNA
      isolated from a human stomach library was sequenced along with the cDNA derived
      from HeLa cells. Western blotting and immunohistochemical analyses of human and
      animal tissues were performed using CA IX-specific monoclonal antibody and rabbit
      antiserum to human CA II. RESULTS; Sequence analysis showed no differences
      between the stomach- and HeLa-derived cDNAs. CA IX was detected at the
      basolateral surface of gastric, intestinal, and gallbladder epithelia. In stomach
      tumor samples, expression of CA IX was lost or reduced. CONCLUSIONS: Differential
      distribution of CA IX in normal and tumor tissues is not associated with cDNA
      mutations. Evolutionary conservation in vertebrates as well as abundant
      expression of CA IX protein in normal human gastric mucosa, but not in derived
      tumors, indicate its physiological importance.

PMID- 9024292
TI  - Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by
      the specific antagonist delays healing in mice.
AB  - BACKGROUND & AIMS: The role of two forms of cyclooxygenase (COX-1 and COX-2) in
      gastric mucosal lesions is not well understood. The regulation of both forms of
      COX and the effect of COX-2 on the repair process of gastric mucosal lesions in
      mice were investigated. METHODS: Gastric mucosal erosions and ulcers were induced
      experimentally in mice. The level of COX messenger RNA (mRNA) was determined by
      reverse-transcription polymerase chain reaction. COX proteins were detected by
      Western blot analysis, and COX activity was determined in the presence or absence
      of NS-398, a specific COX-2 antagonist. The effects of long-term administration
      of NS-398 on gastric ulcers were examined. RESULTS: COX-2 mRNA levels were not
      detected in control conditions but were high during the acute stages of gastric
      erosions and ulcers. COX-2 protein was detected 5 days after ulcer induction but
      not in control mice. Gastric ulceration was not associated with a change in COX-1
      mRNA and protein levels. Administration of NS-398 to mice with ulcers at acute
      stages impaired the healing of ulcers. CONCLUSIONS: High levels of COX-2 mRNA and
      protein during the acute stages of gastric mucosal lesions may be involved in the
      repair process of these lesions in mice.

PMID- 9024294
TI  - Central vagal activation increases mucus gel thickness and surface cell
      intracellular pH in rat stomach.
AB  - BACKGROUND & AIMS: Central vagal stimulation induced by the thyrotropin-releasing
      hormone analogue RX 77368 injected intracisternally in urethane-anesthetized rats
      is gastroprotective. In an in vivo system, the effects of central RX 77368 on
      discrete components of the rat gastric mucosal barrier were studied to determine
      if these effects were prostaglandin synthesis dependent. METHODS: Using
      intravital microscopy, intracellular pH of gastric surface cells, mucus gel
      thickness, gastric mucosal blood flow, and acid output were measured
      simultaneously in vivo. RESULTS: Intracisternal RX 77368 significantly increased
      acid output, gel thickness, and blood flow. Indomethacin enhanced the RX 77368
      induced increase in acid output but had no effect on measures of gastric defense
      during mucosal superfusion with neutral solutions. During acid superfusion, RX
      77368 delayed acidification and enhanced recovery of surface cell intracellular
      pH. These latter effects were reversed partially by indomethacin. Omeprazole
      abolished RX 77368-induced acid secretion but did not alter its effects on
      gastric defense mechanisms. CONCLUSIONS: In response to central vagal stimulation
      with RX 77368, gastric defense mechanisms were enhanced through prostaglandin
      dependent and -independent pathways, in contrast to the prostaglandin-independent
      effects of intravenous pentagastrin. RX 77368-induced enhancements of gastric
      defense mechanisms did not occur as a result of acid secretion.

PMID- 9024295
TI  - Alterations in duodenal bicarbonate secretion and mucosal susceptibility to acid
      in diabetic rats.
AB  - BACKGROUND & AIMS: The gastroduodenal mucosal susceptibility to ulcerogenic
      stimuli increases in diabetic conditions, but the mechanism is unknown. The aim
      of this study was to investigate alterations in duodenal HCO3- secretory response
      in diabetic animals. METHODS: The experiments were performed in rats treated with
      streptozotocin (70 mg/kg intraperitoneally) after 1-6 weeks of diabetes, when
      blood glucose levels were > 300 mg/dL. HCO3 secretion was measured in the
      proximal duodenal loop of rats that were under urethane anesthesia using a pH
      stat method. RESULTS: The duodenal HCO3 secretion induced by mucosal
      acidification was decreased in streptozotocin-treated rats depending on the
      duration of diabetes. The HCO3 secretion was also decreased in response to 16,16
      dimethyl prostaglandin E2, vasoactive intestinal polypeptide, or vagal electrical
      stimulation. Acid load in the duodenum produced extensive damage in 5-6-week
      diabetic rats, although the same treatment caused only slight damage in the
      normal rat duodenum. Such alterations in the duodenal HCO3 secretory and
      ulcerogenic responses in diabetic rats were partially restored by daily injection
      of insulin. CONCLUSIONS: The results suggest that streptozotocin-diabetic
      conditions impair the duodenal HCO3- secretion in rats, possibly as a result of
      decreased sensitivity of the epithelial cell and dysfunction of neuronal pathway,
      thereby increasing the mucosal susceptibility to acid injury in the duodenum.

PMID- 9024296
TI  - Parenteral nutrition modifies glucose and glutamine metabolism in rat isolated
      enterocytes.
AB  - BACKGROUND & AIMS: After small bowel resection, parenteral nutrition is often
      required to provide energy and nitrogen supplies and also to stimulate intestinal
      adaptation, despite the absence of glutamine in formulas. The aim of this study
      was to investigate the effect of nutrient supply route on fuel utilization by
      enterocytes. METHODS: Rats received an intravenous or intragastric continuous
      infusion of an all-in-one glutamine-free formula. Sham-operated control rats were
      orally fed and received the same protein-caloric supplies as the other two
      groups. On day 7, the rats were killed in the fed state, blood samples were
      collected, and the jejunoileum was removed. Enterocytes were isolated. Aliquots
      of cell suspensions were incubated (30 minutes at 37 degrees C) in the presence
      of [14C]glucose and [14C]glutamine (2 mmol/L). Substrate utilization was
      determined by measuring metabolites and CO2 generated. RESULTS: Intravenously fed
      rats showed mild hyperglycemia and marked hyperinsulinemia. Plasma glutamine
      levels were similar in the three groups. Intravenously fed rats showed a
      simultaneous increase in glutamine utilization and a decrease in glucose
      utilization compared with intragastrically fed and control rats, without parallel
      changes in glutaminase and hexokinase activities. The basolateral glucose
      transporter protein concentration was reduced in intravenously fed rat
      enterocytes. CONCLUSIONS: The route of nutrient delivery influences fuel
      utilization by enterocytes.

PMID- 9024297
TI  - Guanosine 3',5'-cyclic monophosphate-dependent protein kinase II mediates heat
      stable enterotoxin-provoked chloride secretion in rat intestine.
AB  - BACKGROUND & AIMS: Escherichia coli heat-stable enterotoxins (STa) provoke
      electrogenic Cl- secretion in the intestine through a guanosine 3',5'-cyclic
      monophosphate (cGMP)-dependent signal transduction pathway. The cGMP receptor
      involved in the activation of the Cl- channel is not known with certainty but may
      comprise either adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein
      kinase (cAK) or cGMP-dependent protein kinase (cGK) type II. The aim of this
      study was to discriminate between these possibilities using specific kinase
      inhibitors. METHODS: Intestinal electrogenic Cl- secretion was determined by
      measuring short-circuit current (Isc) in a Ussing chamber. RESULTS: The general
      protein kinase inhibitors staurosporine and H-8 inhibited rat cGK II activity in
      vitro with 50% inhibitory concentration values of 4 nmol/L and 3 mumol/L,
      respectively, which are lower than those reported for cAK. Both staurosporine and
      H-8, when added to rat proximal colon at concentrations that did not affect the
      Isc response to 8-bromo-cAMPS, inhibited the STa- and 8-bromo-cGMP-provoked Isc
      response for more than 80%. Furthermore, the relative specific cGK inhibitor Rp
      isomer of 8-(chlorophenylthio)-cGMP, but not the cAK inhibitor RP isomer of (Rp)
      8-bromo-cAMPS, inhibited the Isc response to submaximal levels of STa in rat
      proximal colon. CONCLUSIONS: These data provide further evidence for an important
      role of cGK II in STa-mediated Cl- secretion in native rat intestinal epithelium.

PMID- 9024298
TI  - Enhanced growth of small bowel in transgenic mice expressing human insulin-like
      growth factor I.
AB  - BACKGROUND & AIMS: Growth hormone and insulin-like growth factor I (IGF-I)
      stimulate small bowel growth. The aim of this study was to analyze whether IGF-I
      mediates enterotrophic actions of growth hormone. METHODS: IGF-I transgenic mice
      that overexpress an IGF-I transgene driven by the mouse metallothionein I
      promoter and are growth hormone deficient were compared with wild-type
      littermates. Growth of small bowel, abundance and localization of messenger RNAs
      for the IGF-I transgene, and insulin-like growth factor-binding protein 3 were
      assayed. RESULTS: Small bowel length and mass were greater in IGF-I transgenic
      mice than in wild-type mice. Villus height, crypt depth, and crypt cell mitoses
      were greater in jejunum of transgenics than wild-type mice, but jejunal
      disacharidase activities were not increased. The transgene was expressed strongly
      in villus epithelial cells. Insulin-like growth factor-binding protein 3
      messenger RNA was localized in the lamina propria. Regional expression of both
      correlated with the increase in mucosal mass. CONCLUSIONS: Effects of IGF-I
      overexpression on intestinal length and mucosal mass were similar to effects of
      growth hormone overexpression observed previously. Excess of IGF-I increased
      crypt cell proliferation, whereas excess of growth hormone did not increase crypt
      cell proliferation. IGF-I excess stimulated differentiation of intestinal
      epithelial cells less effectively than growth hormone excess.

PMID- 9024299
TI  - Oral calcium phosphate: a new therapy for Crigler-Najjar disease?
AB  - BACKGROUND & AIMS: Calcium phosphate binds unconjugated bilirubin in vitro, and
      dietary calcium phosphate supplementation reduces the serum bilirubin level in
      rats with hereditary unconjugated hyperbilirubinemia (Gunn rats). The aim of this
      study was to evaluate the effect of oral calcium phosphate supplementation on
      plasma bilirubin levels in patients with Crigler-Najjar disease. METHODS: A
      placebo-controlled, double-blind, crossover design was used. Eleven patients, 2
      42 years of age, participated. The group included 5 patients with type I disease
      who were all treated with phototherapy and 6 patients with type II disease who
      were primarily treated with phenobarbital. In addition to plasma bilirubin
      levels, dietary intake and urinary and fecal excretion of calcium and phosphate
      were evaluated. RESULTS: A modest but significant decrease in serum bilirubin was
      observed in patients with type I disease (18% +/- 6%, P = 0.03) but not in
      patients with type II disease during treatment with calcium phosphate. Urinary
      output of calcium and phosphate did not change during the treatment period.
      CONCLUSIONS: Oral calcium phosphate may be a useful adjuvant to photo-therapy in
      Crigler-Najjar type I disease.

PMID- 9024300
TI  - Morbidity and mortality in compensated cirrhosis type C: a retrospective follow
      up study of 384 patients.
AB  - BACKGROUND & AIMS: Few data are available concerning the long-term prognosis of
      chronic liver disease associated with hepatitis C virus infection. This study
      examined the morbidity and survival of patients with compensated cirrhosis type
      C. METHODS: A cohort of 384 European cirrhotic patients was enrolled at seven
      tertiary referral hospitals and followed up for a mean period of 5 years.
      Inclusion criteria were biopsy-proven cirrhosis, abnormal serum aminotransferase
      levels, absence of complications of cirrhosis, and exclusion of hepatitis A and B
      viruses and of metabolic, toxic, or autoimmune liver diseases. RESULTS:
      Antibodies against hepatitis C virus were positive in 98% of 361 patients tested.
      The 5-year risk of hepatocellular carcinoma was 7% and that of decompensation was
      18%. Death occurred in 51 patients (13%), with 70% dying of liver disease.
      Survival probability was 91% and 79% at 5 and 10 years, respectively. Two hundred
      five patients (53%) were treated with interferon alfa. After adjustment for
      clinical and serological differences at baseline between patients treated or not
      treated with interferon, the 5-year estimated survival probability was 96% and
      95% for treated and untreated patients, respectively. CONCLUSIONS: In this cohort
      of patients, life expectancy is relatively long, in agreement with the morbidity
      data showing a slowly progressive disease.

PMID- 9024301
TI  - Primary prophylaxis of variceal bleeding in cirrhosis: a cost-effectiveness
      analysis.
AB  - BACKGROUND & AIMS: Prophylaxis against the first variceal bleeding has been
      proposed to reduce morbidity and mortality in cirrhotic patients. No previous
      information is available regarding the cost-effectiveness of prophylaxis. The aim
      of this study was to compare the cost-effectiveness of variceal bleeding
      prophylaxis with propranolol, sclerotherapy, and shunt surgery in cirrhotic
      patients stratified by bleeding risk. METHODS: A hypothetical cohort was
      stratified according to bleeding risk. The natural history of cirrhosis with
      esophageal varices was simulated using a Markov model. Transitional probabilities
      extracted from published studies and costs were obtained from our institution's
      billing department. Sensitivity analyses were performed for important variables.
      RESULTS: Propranolol results in cost savings ranging between $450 and $14,600
      over a 5-year period. The extent of cost savings depended on the individual
      patient's bleeding risk. In addition, propranolol increased the quality-adjusted
      life expectancy by 0.1-0.4 years. Sclerotherapy was significantly less cost
      effective than propranolol and had no advantage on quality of life. Shunt surgery
      was effective therapy for prevention of bleeding but decreased life expectancy
      and quality of life in some risk groups and was not cost-effective. CONCLUSIONS:
      Propranolol is the only cost-effective form of prophylactic therapy for
      preventing initial variceal bleeding in cirrhosis regardless of bleeding risk.

PMID- 9024302
TI  - Alcohol dehydrogenase: a target of humoral autoimmune response in liver disease.
AB  - BACKGROUND & AIMS: Liver-specific membrane lipoprotein (LSP) is a heterogeneous
      liver preparation that has been widely used to study autoreactivity in liver
      disease. The aim of this study was to identify autoantigens in LSP. METHODS:
      Guinea pig anti-LSP serum was used to screen a human liver complementary DNA
      (cDNA) library. Humoral immune responses to isolated potential autoantigens were
      investigated by immunoblotting in 91 pediatric patients with various liver
      diseases, 20 adult patients with alcoholic liver disease and 20 with autoimmune
      thyroid disease, 37 healthy children, and 20 healthy adults. RESULTS: A 1.6
      kilobase cDNA insert isolated from the cDNA library was found to encode amino
      acids 61-374 of the human alcohol dehydrogenase (ADH)-gamma 1 subunit. Antibodies
      to this or other ADH subunits were found significantly more frequently in
      autoimmune liver diseases (19 of 39 patients; 49%), Wilson's disease (5 of 13
      patients; 38%), and alcoholic liver disease (10 of 20 patients; 50%) than in
      normal controls (P < 0.0001, P < 0.005, and P < 0.05, respectively) and
      correlated with disease activity in autoimmune liver disease. CONCLUSIONS: ADH
      has been identified as a new antigenic component of the LSP using a xenogeneic
      antiserum to immunoprobe a human cDNA liver library and seems to be a target
      autoantigen in liver disease. This approach may be useful in identifying other
      potential autoantigens.

PMID- 9024303
TI  - Telomerase activity and telomere length in hepatocellular carcinoma and chronic
      liver disease.
AB  - BACKGROUND & AIMS: The maintenance of the telomere to a certain length is
      considered to be vital for cellular immortality. Recently, the presence of
      telomerase, an enzyme that elongates telomere length, was reported in various
      malignancies. The aim of this study was to characterize telomerase activity and
      telomere length in hepatocellular carcinoma and chronic liver diseases to
      facilitate better understanding and more accurate diagnosis of hepatocellular
      carcinoma. METHODS: In tumorous and nontumorous tissues from 26 hepatocellular
      carcinomas and from 20 liver tissues without overt hepatocellular carcinoma,
      telomerase activity was examined by telomeric repeat amplification protocol and
      telomere length was detected by Southern blot hybridization method. RESULTS:
      Telomerase activity was detected in 22 of 26 (85%) hepatocellular carcinoma
      specimens. In contrast, it was weakly detected in 4 of 46 (9%) nonneoplastic
      tissues. Telomere length in hepatocellular carcinoma was shorter than that of
      corresponding nontumorous tissue in 44% and longer in 17%. CONCLUSIONS: The
      presence of telomerase activity was confirmed in a majority of cases with
      hepatocellular carcinoma, and alteration of telomere length from nonneoplastic
      tissue was observed in approximately two thirds of hepatocellular carcinomas.
      Therefore, these markers might be good indicators for the diagnosis of
      hepatocellular carcinoma.

PMID- 9024304
TI  - Complete regression of established murine hepatocellular carcinoma by in vivo
      tumor necrosis factor alpha gene transfer.
AB  - BACKGROUND & AIMS: Although tumor necrosis factor (TNF)-alpha possesses a potent
      antitumor activity, systemic administration of TNF-alpha causes severe side
      effects. To circumvent this, the efficacy of tumor cell-targeted TNF-alpha gene
      therapy was investigated. METHODS: Murine hepatocellular carcinoma (HCC) cells
      were infected with MNSM-Alb e/p-TNF-alpha retroviruses carrying the murine TNF
      alpha gene under the transcriptional control of the murine albumin gene promoter,
      and antitumor effects induced by TNF-alpha gene transfer were examined in vitro
      and in vivo. RESULTS: Although MNSM-Alb e/p-TNF-alpha retrovirally infected HCC
      cells showed the same in vitro cell growth as parental HCC cells, they lost their
      tumorigenicity when implanted in syngeneic mice and induced tumor immunity
      against parental HCCs. The retrovirally infected HCC cells also significantly
      inhibited the tumorigenicity of previously implanted parental HCCs. Furthermore,
      intratumoral administration of MNSM-Alb e/p-TNF-alpha retroviruses showed the
      antitumor effect against established HCCs, resulting in significantly prolonged
      survival periods. Most importantly, intratumoral implantation of MNSM-Alb e/p-TNF
      alpha retroviral-producing cells completely abrogated established HCCs in mice.
      CONCLUSIONS: These results indicate the potential efficacy of transferring the
      TNF-alpha gene via retroviral vectors directly into tumors for gene therapy
      against HCCs.

PMID- 9024305
TI  - Increased levels of the multidrug resistance protein in lateral membranes of
      proliferating hepatocyte-derived cells.
AB  - BACKGROUND & AIMS: The multidrug resistance protein (MRP) functions as an organic
      anion efflux carrier. Recent studies suggest that hepatocytes contain two mrp
      homologues, named mrp1 and mrp2, localized on the lateral and canalicular
      membrane, respectively. The aim of this study was to evaluate the role of MRP1.
      Protein levels and localization of MRP1 in human hepatocytes, HepG2 hepatoma
      cells, and SV40 large T antigen-immortalized human hepatocytes were studied.
      METHODS: Using specific antibodies, MRP1 protein levels and cellular localization
      were examined by Western blotting and fluorescence confocal microscopy,
      respectively. In addition, a fluorescent substrate, glutathione
      methylfluorescein, was used to measure plasma membrane transport activity and to
      observe intracellular transport activity. RESULTS: The level of MRP1 in normal
      hepatocytes is very low. In contrast, MRP1 is highly increased in both HepG2 and
      immortalized hepatocytes. In these cells MRP1 is localized in lateral membranes
      of adjacent cells. Plasma membrane staining is absent in separate cells.
      Glutathione-methylfluorescein is transported in the medium and intracellular
      vesicles. CONCLUSIONS: MRP1 protein level is greatly increased in the lateral
      membrane of proliferating hepatocyte-derived cells. The presence of a lateral
      domain seems necessary for plasma membrane localization. These results suggest
      that MRP1-mediated organic anion transport is important in proliferating
      hepatocytes, but not in quiescent cells.

PMID- 9024306
TI  - Focal adhesion kinase and phospholipase C gamma involvement in adhesion and
      migration of human hepatic stellate cells.
AB  - BACKGROUND & AIMS: Hepatic stellate cells (HSCs) play a key role in the
      development of liver fibrosis. Integrin receptors contribute to the regulation
      cell adhesion and migration. The aim of this study was to evaluate the
      interaction between focal adhesion kinase (FAK) and phospholipase C gamma (PLC
      gamma) potentially involved in HSC integrin-mediated signaling pathways. METHODS:
      Interaction between FAK and PLC gamma was determined by immunoprecipitation and
      immunoblotting. HSC chemotactic activity was evaluated using the Boyden chamber
      technique. RESULTS: HSC adhesion to extracellular matrix components (collagen
      type I and IV, laminin, and fibronectin) and antibody-mediated beta 1 ligation
      elicited increased tyrosine phosphorylation of FAK. HSC adhesion to different
      extracellular matrix components did not result in PLC gamma tyrosine
      phosphorylation. However, HSC adhesion induced association between PLC gamma and
      FAK. All extracellular matrix components tested stimulated HSC chemotactic
      activity only at high concentrations. On the contrary, platelet-derived growth
      factor, homodimer BB (PDGF-BB), was able to stimulate HSC migration in a dose
      dependent manner; this event, occurring in the presence of FAK phosphorylation,
      was associated to a dose-dependent PLC gamma tyrosine phosphorylation.
      CONCLUSIONS: These findings provide the first evidence that PLC gamma recruitment
      by FAK during HSC adhesion is an important process implicating a link between
      integrin and PDGF-mediated signaling pathways to regulate HSC adhesion and
      motility.

PMID- 9024307
TI  - Retinoids inhibit adhesion to laminin in human pancreatic carcinoma cells via the
      alpha 6 beta 1-integrin receptor.
AB  - BACKGROUND & AIMS: The initial step in tumor invasion and metastasis is
      determined by adhesion of tumor cells to basement membranes. To evaluate their
      potential therapeutic use in controlling local growth and metastasis, the effects
      of retinoids on the adhesive properties in the human pancreatic carcinoma cell
      line DAN-G were examined. METHODS: The effects of retinoids on cellular adhesion
      were assessed by adhesion assays in vitro. The expression of laminin-binding
      proteins was characterized by Northern blotting, radioimmunoprecipitation, and
      flow-cytometric analysis. RESULTS: Treatment with retinoids results in a time-
      and dose-dependent inhibition of DAN-G cell adhesion to fibronection and laminin
      but not to collagens I, IV, and VI. The adhesion of DAN-G cells to laminin could
      be blocked completely by anti-alpha 6 and anti-beta 1 antibodies but not by the
      synthetic peptide YIGSR. Flow-cytometric analysis of DAN-G cells showed no
      quantitative difference for alpha 6-integrin expression in retinoid-treated and 
      untreated DAN-G cells. Furthermore, radioimmunoprecipitation showed no difference
      in the appearance of alpha 6 beta 1-integrin expression after retinoid
      incubation. CONCLUSIONS: Retinoids decrease pancreatic carcinoma cell adhesion to
      laminin via an as yet unidentified mechanism involving alteration of the alpha 6
      beta 1-integrin receptor function and thereby open interesting perspectives for
      the modulation of infiltrative growth and metastasis in pancreatic cancer.

PMID- 9024308
TI  - Localization of rat pancreatitis-associated protein during bile salt-induced
      pancreatitis.
AB  - BACKGROUND & AIMS: Pancreatitis-associated protein (PAP), which is overexpressed
      in pancreatic acinar cells, appears in pancreatic juice and serum after acute
      pancreatitis. The aim of this study was to examine intracellular localization of
      PAP and amylase in healthy rat pancreas and pancreatitis pancreas to ascertain
      PAP transport from the rough endoplasmic reticulum to the zymogen granules into
      the acinar lumen. METHODS: Control rats and rats with taurocholate-induced
      pancreatitis were killed after 24 hours. Pancreata prepared for light and
      electron microscopy were used for amylase and PAP detection with specific
      antibodies. RESULTS: Induced acute pancreatitis disturbed the gross histology and
      ultrastructure of the acinar cells with the formation of new intracellular
      fibrous material into the cytoplasm, which was also found into the acinar lumen.
      PAP is almost absent from normal acinar cells; after acute pancreatitis, it
      appears in rough endoplasmic reticulum, it is strongly present in normal and
      abnormal zymogen granules, and it remains an important component of the fibrous
      material. Except for its exclusive presence in fibrous material, PAP is always
      colocalized with amylase in the other cell compartments. CONCLUSIONS: These
      observations show that the accumulated PAP into the acinar cells in response to
      acute pancreatitis behaves like all the other secretory proteins with the
      exception that it also accumulates in a new fibrillous cellular structure also
      found in the acinar lumen.

PMID- 9024309
TI  - Neutrophil elastase inhibitor reduces neutrophil chemoattractant production after
      ischemia-reperfusion in rat liver.
AB  - BACKGROUND & AIMS: Neutrophils are important in the development of tissue injury
      induced by ischemia-reperfusion. The ability of an inhibitor of neutrophil
      elastase (ONO-5046) to protect against ischemia-reperfusion injury in rat liver
      was investigated by measuring serum concentrations of cytokine-induced neutrophil
      chemoattractant. METHODS: Liver ischemia was induced in rats by occluding the
      portal vein for 30 minutes, and ONO-5046 or anticoagulants were injected
      intravenously 5 minutes before vascular clamping. RESULTS: Serum concentration of
      cytokine-induced neutrophil chemoattractant increased after reperfusion, reached
      a maximum at 6 hours, and then gradually decreased. However, pretreatment of
      animals with heparin (50 U/kg), antithrombin III (250 U/kg), or ONO-5046 (10
      mg/kg) resulted in significantly smaller increases in the serum concentration of
      cytokine-induced neutrophil chemoattractant after reperfusion. Pretreatment with
      both ONO-5046 and heparin, or both ONO-5046 and antithrombin III, produced
      additive effects. Pretreatment of rats with both ONO-5046 and heparin or both ONO
      5046 and antithrombin III also inhibited the increase in cytokine-induced
      neutrophil chemoattractant mRNA in liver. These combined treatments significantly
      reduced the increases in both the number of neutrophils accumulated in the liver
      and the hepatic activity of myeloperoxidase. CONCLUSIONS: Cytokine-induced
      neutrophil chemoattractant production after ischemia-reperfusion in the liver is
      mediated by neutrophil elastase and activation of coagulation within the hepatic
      microcirculation.

PMID- 9024310
TI  - Multiple hyperplastic polyps in the stomach: evidence for clonality and
      neoplastic potential.
AB  - The origin and neoplastic potential of gastric epithelial polyps remains an area
      of great interest, and treatment choices are a topic of controversy. This report
      describes a patient diagnosed with three concurrent hyperplastic gastric polyps
      that were studied for genetic alterations. The polyps were investigated for
      alterations in the K-ras oncogene and the p53 tumor suppressor gene and for
      p21WAF1/Cip1 and MDM2 protein overexpression. In addition, loss of heterozygosity
      at several loci that are frequently involved in human cancer was analyzed,
      microsatellite instability, a hallmark of the "mutator" phenotype, was
      determined, and Epstein-Barr virus infection was investigated. All separate areas
      from the three independent polyps harbored the same activating point mutation in
      codon 12 of the K-ras oncogene, indicating a clonal origin. DNA sequence
      alterations in p53 were not found, although high p53 protein levels could be
      shown by immunohistochemistry in areas of carcinoma within the largest polyp. No
      alterations in any of the other molecular markers were observed. The results
      strongly favor a clonal origin of the three independent gastric polyps and
      support the notion that these hyperplastic polyps may carry a risk for
      malignancy.

PMID- 9024311
TI  - Primary cardiac gastrinoma causing Zollinger-Ellison syndrome.
AB  - Primary cardiac tumors are rare, and there are no reports of patients with a
      functional gastroenteropancreatic tumor syndrome caused by such a tumor. This
      case report describes a patient with a cardiac gastrinoma causing Zollinger
      Ellison syndrome. Evidence is presented that this tumor represents a primary
      cardiac tumor. The exact identification of this gastrinoma in an extra-abdominal
      site was facilitated by the use of [111In-DTPA-DPhe1]octreotide scanning for
      somatostatin receptors, which these tumors characteristically possess in high
      numbers. The recent availability of this novel localization method may facilitate
      identification of extra-abdominal sites in an increasing proportion of patients
      with gastrinomas and related neuroendocrine functional tumors in which no intra
      abdominal primary tumor is currently found.

PMID- 9024312
TI  - Hepatitis C after orthotopic liver transplantation.

PMID- 9024313
TI  - Approaches to the diagnosis of gut neuroendocrine tumors: the last word (today).
AB  - Because SRS identifies 90% of hepatic metastatic disease and the addition of
      other studies (ultrasonography, C.T. MRI, and selective mesenteric angiography)
      identities only 4% more, the identification of a primary lesion with SRS obviates
      for the most part the use of further investigations. If SRS is negative,
      additional studies should only be undertaken if surgery is contemplated. Because
      SRS may only localize 60%-70% of primary gut NETs, an additional 10%-15% may be
      identified by undertaking additional studies. The most sensitive test, STIR-MRI,
      should be undertaken next, but because it is not widely available, pancreatic
      protocol CT scan is almost as effective in identification of a primary lesion. If
      a primary gastrinoma cannot be identified by SRS or STIR-MRI, endoscopic
      ultrasonography should be undertaken because duodenal gastrinomas are often
      minute and multicentric. A similar strategy applies for insulinomas because up to
      40% cannot be located by SRS and the majority are located in the pancreatic head.
      Thus, STIR-MRI followed by endoscopic ultrasonography is the most appropriate
      course. Although calcium provocation-angiography is highly effective in the
      identification of insulinomas, it is significantly more invasive and should be
      used only as a last resort. Of particular interest is the observation that in the
      study of gastrinomas, SRS altered clinical management in almost 50% of patients.
      This reflected the ability of SRS not only to identify the primary tumor location
      but clarify equivocal localization results generated by conventional imaging
      studies. It thus seems that the simplicity, superior sensitivity, high
      specificity, and cost-effectiveness of SRS mandate that it be the imaging
      modality in patients with gastrinomas. Because the cost of an SRS is $1800 and
      may obviate the need for multiple other topographic studies that are at least as
      expensive, the fiscal dictates further warrant the use of this study as the
      initial topographic investigation. These observations are probably applicable to
      all gut NETs, although the likelihood of primary identification in the instance
      of insulinoma patients may be somewhat less. The timely and cost-effective
      establishment of the type of NET, its primary site, and the detection metastatic
      spread will enable determination of the appropriate management strategy.

PMID- 9024314
TI  - The centennial year: the development of important ideas during the last 100
      years. The advent and evolution of endoscopy.

PMID- 9024315
TI  - Colorectal cancer screening: clinical guidelines and rationale.

PMID- 9024316
TI  - Hereditary mixed polyposis syndrome: a zebra or a horse dressed in pinstripes.

PMID- 9024317
TI  - Cyclooxygenase 2 and wound healing in the stomach.

PMID- 9024318
TI  - Crigler-Najjar disease type I: therapeutic approaches to genetic liver diseases
      into the next century.

PMID- 9024319
TI  - The natural history of chronic hepatitis C and what we should do about it.

PMID- 9024320
TI  - Gene therapy for hepatocellular carcinoma: progress but many stones yet unturned!

PMID- 9024321
TI  - Erythropoietin for inflammatory bowel disease anemia.

PMID- 9024322
TI  - Surveillance for Barrett's esophagus: are we saving lives?

PMID- 9024323
TI  - How do epithelial cells respond to stress?

PMID- 9024324
TI  - Fecal occult blood testing: beyond hemoccult.

PMID- 9024325
TI  - Viewpoints in intestinal permeability.

PMID- 9024326
TI  - Role of the host in Helicobacter disease.

PMID- 9024327
TI  - Prostaglandins in liver transplantation: a $50,000 bonus.

PMID- 9024328
TI  - Does gluten sensitivity always imply celiac disease?

PMID- 9024329
TI  - Gamma-aminobutyric acid-induced chloride secretion.

PMID- 9024330
TI  - Neurobiology of Alzheimer's disease.
AB  - Although the specific process that destroys neurons in patients with Alzheimer's
      disease (AD) remains obscure, biochemical studies of AD neurohistologic lesions
      and molecular attempts to map and clone genes in familial AD have contributed
      greatly to our knowledge of AD. The major component of the extraneuronal neuritic
      plaque is beta-amyloid (A beta), which may be neurotoxic. The major component of
      the intraneuronal neurofibrillary tangle is hyperphosphorylated tau protein. It
      is unclear why this process damages the neuronal cytoskeleton Familial AD is
      genetically heterogeneous. Chromosomes 21, 14, and 1 are causative genes in early
      onset familial AD. The apolipoprotein E4 allele of chromosome 19 is a risk factor
      for both early- and late-onset AD. Unraveling the actions of these three
      causative genes and the apolipoprotein E4 allele may explain disease mechanisms
      common to all patients with AD.

PMID- 9024331
TI  - Neuroimaging and genetic assessment for early diagnosis of Alzheimer's disease.
AB  - Identifying persons with mild cognitive complaints who are at risk for
      Alzheimer's disease (AD) will enable the start of antidementia treatments before
      extensive brain damage develops. Recent research developments link the
      apolipoprotein E-4 (APOE-4) allele to late-onset familial and late-onset sporadic
      AD. Studies of relatives at risk for familial AD using brain imaging (positron
      emission tomography [PET]) and genetic assessments suggest that relatives with
      the APOE-4 allele have lower parietal metabolism than those without this allele.
      Approaches that might increase sensitivity and specificity include, among others,
      pharmacologic challenges of short-acting anticholinergic agents and memory
      activation during functional scanning. Such strategies should eventually assist
      in early detection of AD and in vivo therapeutic monitoring of brain function
      during experimental antidementia treatment trials.

PMID- 9024332
TI  - The treatment of depressed demented patients.
AB  - Problems in diagnosing depression and unclear pharmacologic guidelines may reduce
      the use and efficacy of antidepressant treatment in depressed demented patients.
      Data from the few controlled studies involving patients with depression and
      dementia suggest that tricyclic antidepressants improved depressive
      symptomatology in more than 50% of patients. However, comparable improvement has
      been reported with placebo. Cognitive dysfunction in elderly patients with
      depression appears to alter tricyclic plasma concentration-efficacy
      relationships. Enlargement of lateral brain ventricles may be associated with
      poor response to tricyclics as well as altered plasma concentration-efficacy
      relationships. There is some evidence that nontricyclic antidepressants may be
      effective in demented patients with depression. An emerging pharmacology for
      cerebrovascular disease may have relevance in treating and preventing several
      geriatric depressive syndromes, but specific studies are needed.

PMID- 9024333
TI  - Treatment strategies for agitation and psychosis in dementia.
AB  - Agitation or psychosis or both occur in half or more of patients with dementia at
      some point during the course of illness. The treatment of these signs and
      symptoms ideally entails identification and alteration of physical,
      environmental, social, and psychiatric factors. Environmental modification,
      education of caregivers, and therapeutic activity programs are nonpharmacologic
      approaches that can effectively reduce some signs and symptoms of this nature.
      For those that remain, empirical administration of pharmacologic agents may be
      appropriate. One approach is to inventory the specific behaviors and develop a
      "therapeutic metaphor," i.e., subtype the agitated behaviors according to the
      presence of target symptoms likely to respond to specific classes of medication.
      Available evidence is reviewed regarding the efficacy and safety of somatic
      therapies for agitation, including antipsychotics, antidepressants,
      anticonvulsants, benzodiazepines, and cholinesterase inhibitors.

PMID- 9024334
TI  - New therapeutic approaches to Alzheimer's disease.
AB  - Therapeutic approaches to treat the cognitive impairment in dementia and to treat
      slow decline are making their way into clinical practice. Cholinergic agents are
      currently the most promising treatment, and several cholinesterase inhibitors
      will soon be available for prescription. As physicians learn more about dosing,
      side effects, and mechanisms of action, they can prescribe these drugs more
      efficiently. Evidence suggests that certain patients with dementia may be
      particularly responsive to such intervention, and other medications may enhance
      response. Current experimental approaches to slowing the rate of cognitive
      decline include the use of antioxidants, monoamine oxidase-B inhibitors,
      cholinesterase inhibitors, and anti-inflammatory agents. Psychosocial
      interventions appear to help delay institutionalization. Drugs that improve
      cognition also may affect behavioral symptoms and severe dementia as well as non
      Alzheimer dementia.

PMID- 9024335
TI  - Developing treatment guidelines for Alzheimer's disease and other dementias.
AB  - Developing treatment guidelines for Alzheimer's disease and other dementias
      depends primarily on a literature review. A recent review suggests that tacrine
      is modestly effective in treating cognitive symptoms and that-neuroleptic drugs
      are modestly effective in treating agitation and aggression. Few randomized,
      double-blind, placebo-controlled trials of other agents used for the treatment of
      cognitive and noncognitive symptoms of dementia have been performed. A variety of
      behavioral/environmental interventions show modest but nonspecific effects in
      treating Alzheimer's disease and other types of dementia. Family-focused support
      interventions are moderately effective and may delay nursing home placement.

PMID- 9024336
TI  - Dental health services research and education.

PMID- 9024337
TI  - The role of health services research in the renaissance of the dental profession.
AB  - Health services research may play a critical role in achieving the
      recommendations of the IOM study. Toward this end, the field of health services
      research is defined. Applications of health services research to health outcomes,
      patient care, and other IOM directives are reviewed. Alternative approaches to
      building the capacities of dental schools to conduct health services research are
      presented.

PMID- 9024338
TI  - Dentist-patient interactions in treatment decision-making: a qualitative study.
AB  - The growing involvement of patients, third party payers, and government in the
      financing, planning, and delivery of health services has heightened the demand
      for knowledge about the process of rendering care. This study used a qualitative
      methodology to examine dentist-patient interactions in treatment decision-making.
      A series of focus groups was conducted with dentists and patients participating
      in an ongoing investigation of dental treatment planning conducted at the
      University of North Carolina. Study findings indicate that dentist-patient
      interactions play an important role in treatment decision-making and that both
      are predicated on a variety of non-clinical factors. Dentists' intuition and
      judgment seem to be used not only to select desired health outcomes and the means
      for achieving them, but also to depart from the ideal and/or to modify treatment
      plan presentation on a patient-to-patient basis. Patients' impressions of
      dentists' examination styles, personalities, and ability to relate to them as
      individuals seem to mediate both treatment acceptance and willingness to
      participate in the decision-making process. Results of this investigation suggest
      that any effort aimed at improving dental treatment decision-making needs to
      acknowledge the interplay of clinical and psychosocial factors.

PMID- 9024339
TI  - Variation in the use of crowns and their alternatives.
AB  - The use of crowns and their alternatives for the restoration of compromised
      posterior teeth is of interest to educators, purchasers, and patients.
      Considerable curricular time is devoted to learning these techniques, substantial
      amounts of money are spent on these procedures, and differences in the outcomes
      of these treatments may have consequences for tooth survival. To begin to
      understand more about the actual use of these procedures, the provision rates of
      these services in a sample of U.S. dental practices were examined. This study
      reports on the extent to which utilization patterns and subsequent costs of
      crowns and their alternatives were associated with certain patient and practice
      characteristics. Insurance claims for dental services submitted by general dental
      practices through an electronic claims clearinghouse were used. Crown ratios
      (crowns/crowns plus alternatives) were calculated for dental practices to
      evaluate relationships with available explanatory variables. Findings indicated
      that older patients were significantly more likely to receive crowns than those
      in younger groups, resulting in as much as a 33 percent increase in the mean per
      tooth cost of treatment in the oldest group. Regional variation existed in the
      provision of crowns and resulted in up to a 31 percent difference in the mean per
      tooth treatment cost between regions. Crown ratios exhibited variation beyond
      that accounted for by patient and practice factors, thus raising questions about
      the consistency of treatment recommendations among dentists. These findings
      support the need to examine further the consistency of crown use among general
      dentists and to modify current approaches for teaching treatment planning in
      predoctoral restorative curricula.

PMID- 9024340
TI  - Orthodontic residents' indications for use of the lateral TMJ tomogram and the
      posteroanterior cephalogram.
AB  - The purpose of this study was to determine the selection criteria used by
      orthodontic residents for ordering a corrected lateral tomogram (LT) of the
      temporomandibular joint (TMJ) and a posteroanterior cephalogram (PAC) for the
      diagnosis of patients needing orthodontic care. The impact of the radiographs on
      their treatment plans was also assessed. We conducted a study of the 144 new
      patients assigned to eight orthodontic residents during a two-year period. The
      residents responded through questionnaires describing their rationale for
      ordering the radiographs. A LT was ordered for twenty-eight (19 percent) of the
      patients. The most common reasons cited for requesting the LTs were TMJ clicking
      (67 percent) and pain (33 percent). The residents also perceived a need to order
      the LT for medico-legal protection in 85 percent of these cases. The LT tended
      not to have an impact on treatment planning. A PAC was ordered thirty-eight times
      (26 percent). The most common reasons cited by residents for ordering a PAC
      included clinical findings of facial asymmetry (41 percent) and maxillary airway
      anatomy (24 percent). Medico-legal protection was a perceived need in only 12
      percent of the cases. While the PAC had no impact on treatment planning for 56
      percent of the cases, they did define the transverse problems as dental or
      skeletal for 38 percent of the cases. Six patient traits were statistically
      associated with PAC requests: difficulty chewing, abnormal TMJ, TMJ clicking,
      facial asymmetry. crossbite, and midline discrepancy. The teaching of appropriate
      selection criteria for ordering these radiographs needs to be emphasized early in
      a resident's training.

PMID- 9024341
TI  - The sensitivity of the Geriatric Oral Health Assessment Index to dental care.
AB  - The sensitivity of the Geriatric Oral Health Assessment Index (GOHAI) to dental
      treatment was evaluated using data from a community-based oral health promotion
      project. Ninety-six subjects completed baseline and twenty-four-month follow-up
      interviews that included the GOHAI as well as other self-reported measures of
      oral health. Subjects were predominantly white, female, not currently married,
      with less than a high school education, and had average age of seventy-six years
      at baseline. Through the health promotion project, participants were offered low
      cost diagnostic and preventive services on a sliding fee basis. At twenty-four
      months, subjects' records were abstracted regarding the receipt of dental
      hygiene, transportation, emergency, diagnostic, restorative, and prosthodontic
      services. Subjects were also asked about dental expenditures in the previous year
      and the type of dental care received, regardless of the source of care. The mean
      change in GOHAI scores from baseline to the twenty-four-month interview was 2.2
      (std. dev. 6.6) and ranged from -15 to 30. Findings suggest that the GOHAI is
      sensitive to the provision of dental care, although additional research is needed
      to understand the impact of various dental services on the individual items of
      the GOHAI, as well as the overall index score. The potential applications of self
      reported oral health outcome measures such as the GOHAI in dental education are
      discussed.

PMID- 9024342
TI  - Dental health services research utilizing comprehensive clinical databases and
      information technology.
AB  - Marketplace pressures for accountability in dentistry have made clear dental
      delivery systems' weaknesses in information generation, management, and analysis
      methods. Without this type of information, dentistry is unable to quantify and
      document the outcomes of the dental care services it provides. The Pew Health
      Professions Commission and the Institute of Medicine both suggest that dental
      schools should be among the leaders in the development and teaching of dental
      information capabilities, as well as the source of fundamental dental health
      services research. This paper argues that dental schools are the logical location
      for the development of valid, reliable, and acceptable health services research
      methods and databases. It describes the development of an insurance claims
      database to demonstrate the types of investigations possible, as well as the
      weaknesses and shortcomings of pure administrative data.

PMID- 9024343
TI  - Using questions to facilitate motor skill acquisition.
AB  - For the process of question-guided problem-solving to work successfully, several
      conditions must exist: 1) presence of valid and reliable criteria for evaluating
      product (DO) and performance (DP), 2) development of learning resources such as
      life-sized examples, 3) training sessions in the application of criteria and use
      of the process for both faculty and students, and 4) faculty commitment to the
      process. The process helps to establish conditions in which learning occurs.
      Underlying its structure is the requirement for incorporation of discrimination
      tasks. Question-guided problem-solving structures the learner's approach to the
      task in a way that facilitates the refinement of independent learning strategies
      over time. Further, it promotes effective use of time in laboratory or clinic.
      Through repeated interactions, the faculty may better monitor student progress,
      diagnose student learning problems, suggest remedial strategies, and evaluate
      their outcomes. By providing instruction that includes opportunities to practice
      the subskills of problem-solving in an interactive cooperative environment,
      students systematically monitor learning by asking good questions and, through
      questioning, are empowered to solve problems.

PMID- 9024344
TI  - Using collaborative learning in dental education.
AB  - Collaborative learning organizes students into small groups in which they assist
      each other to solve problems and integrate skills and knowledge. Students
      increase self-esteem and develop a more positive attitude toward learning.
      Collaborative learning can be used in classrooms, laboratories, and clinical
      settings. Learning is accomplished through small-group discussion, with students
      being responsible for helping each other achieve the desired learning outcomes.
      Instructors manage content through the design of the learning activities rather
      than by presenting the material in lectures.

PMID- 9024345
TI  - Giving your patients a sporting chance.

PMID- 9024346
TI  - Diagnosis and management of condylar resorption.
AB  - PURPOSE: This article discusses the cause, appropriate diagnostic evaluation, and
      management of progressive condylar resorption. PATIENTS AND METHODS: This
      retrospective study evaluated 28 adult patients with bilateral progressive
      condylar resorption. Investigation included serial clinical examination, lateral
      cephalograms, tomograms, and a technetium isotope bone scan when indicated.
      Twenty-two patients were managed by either condylectomy and reconstruction with a
      costochondral graft (n = 5 patients) or orthognathic surgery (n = 18 patients).
      One patient initially had orthognathic surgery and subsequently underwent
      condylectomy and costochondral grafting, making a total of 23 procedures on 22
      patients. Six patients received no surgical treatment. All patients were observed
      at least 2 years postoperatively. RESULTS: Of the 18 patients who underwent
      orthognathic surgery, four again demonstrated condylar resorption with recurrence
      of open bite and retrognathism. Four patients had a stable result, but currently
      have temporomandibular joint (TMJ) symptoms, whereas 10 patients had a stable
      result (no change in postoperative occlusion or jaw position) without TMJ
      symptoms. The five cases receiving condylectomy and costochondral grafting were
      stable and asymptomatic, with good mandibular function. Analysis of the 18
      orthognathic surgery patients showed that relapse occurred in patients having
      bimaxillary surgery with mandibular advancements greater than 5 mm and with a
      preoperative posterior ramus height of less than 35 mm. CONCLUSION: The
      management of progressive condylar resorption remains controversial. Orthognathic
      surgery in this small sample was associated with a complication rate (relapse or
      TMJ dysfunction) of approximately 45% (8 of 18). In contrast, condylectomy and
      costochondral grafting appeared to produce stable and functional results. Further
      long-term outcome studies for patients with condylar resorption are needed to
      corroborate these results.

PMID- 9024347
TI  - Effect of mandibular setback surgery on occlusal force.
AB  - PURPOSE: This study investigated the effect of mandibular setback surgery on
      occlusal force and evaluated the extent to which postsurgical changes in such
      force can be explained by the type of operation, the duration of maxillo
      mandibular fixation (MMF), and the changes in the mechanical advantage of the jaw
      musculature. MATERIALS AND METHODS: Maximal molar bite force was measured before
      surgery and at MMF removal, and 3, 6, and 12 months thereafter in 26 patients
      with mandibular prognothism. To correlate bite force and skeletal change, the
      cephalometric tracings were measured, tabulated, and statistically analyzed.
      RESULTS: Mean bite force was 13.7 kg before surgery, 7.6 kg at MMF removal, 14.2
      kg at 3 months, 19.7 kg at 6 months, and 26.1 kg at 12 months post-surgery. The
      bite force was positively correlated with the surgical change in mandibular plane
      angle and mandibular body length. The recovery of bite force was significantly
      affected by the type of operation and duration of MMF. CONCLUSIONS: To hasten
      recovery and increase bite force after orthognathic surgery, long periods of MMF
      and injury to the masticatory muscles should be avoided.

PMID- 9024348
TI  - Desflurane for outpatient general anesthesia in third molar extraction cases.
AB  - PURPOSE: The purpose of this study was to evaluate the use of desflurane, a new
      volatile anesthetic agent, in a standardized endotracheal anesthetic technique
      for the removal of third molars in ambulatory patients. PATIENTS AND METHODS:
      Data were kept on 50 American Society of Anesthesiology (ASA) Class I and II
      patients undergoing oral endotracheal general anesthesia for removal of third
      molars. A standardized anesthetic technique was used on all patients. Induction
      was achieved with a bolus of propofol followed by neuromuscular paralysis with
      succinylcholine and then intubation. A 70% nitrous oxide, 30% oxygen, and
      desflurane mixture was titrated until there was no movement, and a local
      anesthetic was administered. The procedure was then completed in a standard
      fashion. The parameters measured included the length of surgery, the time from
      gas shutoff to extubation, the time from arrival in the postanesthesia care unit
      to achieving an Aldrete system score for discharge with an escort, the incidence
      of nausea and vomiting, and amnesia of the procedure. RESULTS: This study showed
      that the use of desflurane as the primary anesthetic agent for procedures of less
      than 1 hour is a useful technique. The agent is expensive, but the decreased
      recovery time and minimal side effects may offset this expense. CONCLUSION: The
      desflurane anesthetic technique provides a satisfactory surgical environment in
      selected patients. It results in rapid postanesthesia recovery and discharge
      times, thus reducing costs.

PMID- 9024349
TI  - Assessment of the lingual nerve in the third molar region using magnetic
      resonance imaging.
AB  - PURPOSE: The purpose of this study was to determine the precise in situ location
      of the lingual nerve in the third molar region using high-resolution magnetic
      resonance imaging. PATIENTS AND METHODS: Ten healthy volunteers (20 sides) with
      mandibular third molars underwent bilateral axial and coronal high-resolution
      magnetic resonance imaging (MRI) examinations of the posterior mandible and floor
      of the mouth from the lingula to the mental foramen. Three trained individuals
      made measurements of each image to determine the vertical and horizontal position
      of the lingual nerve in the third molar region. RESULTS: The mean vertical (2.75
      +/- 0.97 mm [range, 1.52-4.61]) and horizontal (2.53 +/- 0.67 mm [range, 0.00
      4.35]) distances to the lingual crest and lingual plate of the mandible were
      determined. In the third molar region, there were only 2 of 20 cases (10%) in
      which the nerve was above the lingual crest, and there were 5 of 20 instances
      (25%) in which the nerve was in direct contact with the lingual plate.
      CONCLUSIONS: This study precisely documents the in situ location of the lingual
      nerve in the third molar region, and reconfirms the relative vulnerable position
      of this structure during third molar surgery.

PMID- 9024350
TI  - Radiographic evaluation of mandibular augmentation with prefabricated
      hydroxylapatite/fibrin glue implants.
AB  - PURPOSE: This study radiographically evaluated the stability of mandibular height
      during a 2-year follow-up after augmentation with prefabricated
      hydroxylapatite/fibrin glue (HA/FG) implants. PATIENTS AND METHODS: Standardized,
      lateral oblique cephalometric radiographs were made of 22 patients 6, 12, and 24
      months postoperatively and analyzed with a newly developed, computerized image
      analysis technique. RESULTS: The average height of the HA/FG implants after
      augmentation was 9.45 mm. Average loss of total height of the augmented mandibles
      was 2.31 mm after 6 months, 2.90 mm after 12 months, and 3.93 mm after 24 months.
      Reduction of HA/FG implant height alone was 0.62 mm after 6 months, 1.24 mm after
      12 months, and 2.03 mm after 24 months. Reduction occurred mainly during the
      first 6-month evaluation period and was probably primarily caused by adaptation
      of the implant to the surface of the mandible. An inferior compression of the
      implant or resorption of the alveolar crest and underlying basilar bone are
      possible reasons for loss of total mandibular height. CONCLUSION: The results
      indicate that prefabricated HA/FG implants used for augmentation of edentulous
      mandibles show little reduction in height, but are not completely stable during a
      2-year evaluation period.

PMID- 9024351
TI  - The adenomatoid odontogenic tumor: an analysis of 57 cases in a black African
      population.
AB  - PURPOSE: This study analyzed the findings in a large series of adenomatoid
      odontogenic tumors (AOT) in Nigerians. PATIENTS AND METHODS: Hospital records of
      all cases of AOT diagnosed at three teaching hospitals were reviewed and
      analyzed. RESULTS: Most of the tumors were intraosseous (central) (98.3%) and of
      the follicular type (75%). Females were more frequently affected than males
      (1.4:1), and patients in their second decade of life were most frequently
      affected (75%). Patients with follicular AOT were relatively younger (15.2 +/-
      5.6 years) than those with extrafollicular tumors (20.9 +/- 13.8 years). However,
      males who presented with extrafollicular tumors (14.6 +/- 3.9 years) were
      relatively younger than their female counterparts (24.9 +/- 16 years). The
      maxilla was affected nearly twice as often as the mandible (1.8:1), and the
      canine tooth was frequently embedded in the tumor (76.9%). Although follicular
      tumors were most frequently located in the maxilla (76.3%), extrafollicular
      tumors were more commonly found in the mandible (69.2%). CONCLUSION: The
      distribution of this tumor in black Africans does not appear to be substantially
      different from that reported in caucasians.

PMID- 9024352
TI  - Long-term outcome of arthrocentesis for sudden-onset, persistent, severe closed
      lock of the temporomandibular joint.
AB  - PURPOSE: This study analyzed the long-term effect of arthrocentesis for severe
      closed lock of the temporomandibular joint (TMJ) and reevaluated the pathogenesis
      of this condition based on the data obtained. PATIENTS AND METHODS: Thirty-nine
      patients (40 joints) who had experienced sudden-onset, persistent limited mouth
      opening were the subjects of this study. After unsuccessful noninvasive
      treatment, arthrocentesis of the upper compartment of the affected TMJ was
      performed using saline. The follow-up, which consisted of patient self-assessment
      and clinical examination, ranged from 6 to 37 months (mean, 16.6 +/- 12.0
      months). Visual analog scales were used for preoperative and postoperative self
      evaluation of pain and dysfunction on forced mouth opening and for assessment of
      overall change in these parameters postarthrocentesis. Maximal mouth opening
      (MMO), contralateral movement (CLM) and protrusive movement of the jaw, and
      presence of joint noises were noted preoperatively and at clinical follow-up
      examinations. RESULTS: At 6 to 37 months postarthrocentesis, MMO and CLM had
      increased significantly (from a mean of 23.10 +/- 5.15 mm to 44.25 +/- 4.96 mm,
      and from a mean of 4.81 +/- 2.36 mm to 8.20 +/- 1.90 mm, respectively; P < .001).
      Functional improvement was associated with a significant reduction in pain and
      dysfunction levels (from a mean of 9.24 +/- 2.90 to 1.45 +/- 1.74, and from a
      mean of 9.26 +/- 2.82 to 2.68 +/- 2.80, respectively, on a scale of 0 to 15; P <
      .001). The overall improvement, as expressed in pain and dysfunction levels, was
      about 95%, with no recurrence of severe closed lock. CONCLUSIONS: Arthrocentesis
      for sudden-onset closed lock provided sustained normal joint function and marked
      pain relief. Because the available literature shows that arthrocentesis changes
      neither disc position nor disc shape, it places in doubt the concept of a
      displaced and deformed disc limiting joint function. Rather, the efficacy of
      lavage in resolving closed lock suggests that the condition is the result of
      sudden adherence of the normally shaped disc to the fossa, rendering it incapable
      of sliding. The characteristic features of sudden-onset, limited mouth opening
      warrants classification of this disorder as an independent entity within the
      realm of TMJ disturbances.

PMID- 9024353
TI  - Red-blue lesion of the hard palate.

PMID- 9024354
TI  - Pseudoaneurysm of the superficial temporal artery: report of a case.

PMID- 9024355
TI  - Paresthesia of the cutaneous branch of the mylohyoid nerve after removal of a
      submandibular salivary gland.

PMID- 9024356
TI  - Median lingual cyst: review of the literature and report of a case.

PMID- 9024357
TI  - Outpatient anesthetic management of a patient with Wolff-Parkinson-White
      syndrome.

PMID- 9024358
TI  - Possible malignant transformation of an ameloblastic fibroma to ameloblastic
      fibrosarcoma: a case report.

PMID- 9024359
TI  - Lag screw fixation of a nonstable zygomatic complex fracture: case report.

PMID- 9024360
TI  - Odontogenic keratocyst appearing as a soap-bubble or honeycomb radiolucency:
      report of a case.

PMID- 9024361
TI  - Giant hemangioma of the sternocleidomastoid muscle: report of a case.

PMID- 9024362
TI  - Calciphylaxis causing localized tongue necrosis: a case report.

PMID- 9024363
TI  - Tension-releasing suture in the repair of alveolar cleft defects.

PMID- 9024364
TI  - Combined epithelial odontogenic tumors-fact or fallacy.

PMID- 9024365
TI  - Accepting our responsibility for treating AIDS patients.

PMID- 9024366
TI  - What price cost control?

PMID- 9024367
TI  - Genetic irony beyond haemochromatosis: clinical effects of HLA-H mutations.

PMID- 9024368
TI  - Pre-eclampsia: a case of nerves?

PMID- 9024369
TI  - Has thrombolytic therapy changed the equation for postinfarction risk
      stratification?

PMID- 9024370
TI  - European consensus on viral encephalitis.

PMID- 9024371
TI  - Randomised trial of intravenous salbutamol in early management of acute severe
      asthma in children.
AB  - BACKGROUND: The mainstay of treatment for acute asthma in children is nebulised
      beta 2-adrenergic agents such as salbutamol, given with corticosteroids. However,
      penetration of the drug to the small airways is impeded by obstruction so
      intravenous salbutamol may be more effective. We assessed the use of intravenous
      salbutamol in the management of children with acute severe asthma in a double
      blind randomised study. METHODS: Children who presented to the Emergency
      Department of Westmead Hospital, Sydney, Australia with asthma were assessed with
      a clinical assessment scale, and those with severe acute asthma were given
      nebulised salbutamol at a dose of 2.5 mg (age < or = 2 years) or 5.0 mg (age > 2
      years), made up to 4 mL with saline. Children who did not improve were eligible
      to enter phase one of the study. In this phase (0 h-2 h) treatment was by a
      standard protocol: nebulised salbutamol at the above dose: 4 L/min or 6 L/min
      continuous oxygen until oxygen saturation reached 93% in room air for at least 30
      min; a bolus of intravenous hydrocortisone 5 mg/kg given over 3 min; and then 15
      micrograms/kg intravenous salbutamol or saline, depending on randomised
      allocation. In phase two (2 h-24 h) the children were given nebulised salbutamol
      continuously then at 30 min, 1 h, 2 h, 3 h, and 4 h, according to need. All
      children were transferred to the ward once they were ready to start hourly
      nebulisation. All patients were followed up until discharge. The primary
      endpoints were recovery time (no longer requiring inhaled salbutamol) and
      persistent moderate to severe asthma 2 h after randomisation. Analyses were by
      intention-to-treat although no withdrawals occurred. FINDINGS: The recovery time
      (time to cessation of nebulised salbutamol every 30 min) was 4 h in the 14
      children allocated intravenous salbutamol compared with 11.5 h for the 15
      children in the control group. 2 (14%) of the intravenous salbutamol group
      compared with 8 (53%) of the control group needed oxygen to maintain oxygen
      saturation at 93% room air. The intravenous salbutamol group were ready for
      discharge from the emergency department 9.7 h earlier than the control group. No
      clinically significant side-effects were found in either group. INTERPRETATION:
      Addition of a 10 min infusion of salbutamol in the early treatment of children
      with acute severe asthma has the potential to curtail the clinical progression of
      asthma, reduce demand placed on hospital resources, and improve the quality of
      health care provided to the acutely sick child with asthma.

PMID- 9024372
TI  - Acute ischaemia: a dynamic influence on QT dispersion.
AB  - BACKGROUND: The aim of this study was to test the hypothesis that acute
      myocardial ischaemia increases QT dispersion measured from the 12-lead
      electrocardiogram. METHODS: Incremental atrial pacing was used to induce
      myocardial ischaemia in 18 patients with coronary artery disease and QT
      dispersion was measured. Six patients with normal coronary arteries served as the
      control group. FINDINGS: All the patients with coronary artery disease developed
      angina and/or ST depression accompanied by marked increases in QT dispersion
      (mean increase 38 ms, 95% CI 30 to 45 ms, p < 0.001). In contrast, in the six
      patients with normal coronary arteries who remained without symptoms and without
      ST changes, there was no significant change in QT dispersion in response to
      pacing. Baseline QT dispersion did not distinguish those patients with coronary
      artery disease from those with normal coronary arteries (44 ms [95% Cl 39-49 ms]
      vs 40 ms [25-55 ms]), respectively. INTERPRETATION: These results demonstrate
      that myocardial ischaemia induced by incremental atrial pacing in patients with
      coronary artery disease causes an acute increase in QT dispersion. Such
      "inducible" QT dispersion may prove more useful than resting QT dispersion in
      assessing the individual risk of arrhythmic events in patients with coronary
      artery disease.

PMID- 9024373
TI  - An alternative strategy for studying adverse events in medical care.
AB  - BACKGROUND: Data about the frequency of adverse events related to inappropriate
      care in hospitals come from studies of medical records as if they represented a
      true record of adverse events. In a prospective, observational design we analysed
      discussion of adverse events during the care of all patients admitted to three
      units of a large, urban teaching hospital affiliated to a university medical
      school. Discussion took place during routine clinical meetings. We undertook the
      study to enhance understanding of the incidence and scope of adverse events as a
      basis for preventing them. METHODS: Ethnographers trained in qualitative
      observational research attended day-shift, weekday, regularly scheduled attending
      rounds, residents' work rounds, nursing shift changes, case conferences, and
      other scheduled meetings in three study units as well as various departmental and
      section meetings. They recorded all adverse events during patient care discussed
      at these meetings and developed a classification scheme to code the data. Data
      were collected about health-care providers' own assessments about the
      appropriateness of the care that patients received to assess the nature and
      impact of adverse events and how health-care providers and patients responded to
      the adverse events. FINDINGS: Of the 1047 patients in the study, 185 (17.7%) were
      said to have had at least one serious adverse event; having an initial event was
      linked to the seriousness of the patient's underlying illness. Patients with long
      stays in hospital had more adverse events than those with short stays. The
      likelihood of experiencing an adverse event increased about 6% for each day of
      hospital stay, 37.8% of adverse events were caused by an individual, 15.6% had
      interactive causes, and 9.8% were due to administrative decisions. Although 17.7%
      of patients experienced serious events that led to longer hospital stays and
      increased costs to the patients, only 1.2% (13) of the 1047 patients made claims
      for compensation. INTERPRETATION: This study shows that there is a wide range of
      potential causes of adverse events that should be considered, and that careful
      attention must be paid to errors with interactive or administrative causes.
      Healthcare providers' own discussions of adverse events can be a good source of
      data for proactive error prevention.

PMID- 9024374
TI  - Diagnosis of viral infections of the central nervous system: clinical
      interpretation of PCR results.
AB  - BACKGROUND: Standard laboratory techniques, such as viral culture and serology,
      provide only circumstantial or retrospective evidence of viral infections of the
      central nervous system (CNS). We assessed the diagnostic accuracy of PCR of
      cerebrospinal fluid (CSF) in the diagnosis of viral infections of the CNS.
      METHODS: We examined all the CSF samples that were received at our diagnostic
      virology laboratory between May, 1994, and May, 1996, by nested PCR for viruses
      associated with CNS infections in the UK. We collected clinical and laboratory
      data for 410 patients from Oxford city hospitals (the Oxford cohort) whose CSF
      was examined between May, 1994, and May, 1995. These patients were classified
      according to the likelihood of a viral infection of the CNS. We used stratified
      logistic regression analysis to identify the clinical factors independently
      associated with a positive PCR result. We calculated likelihood ratios to
      estimate the clinical usefulness of PCR amplification of CSF. FINDINGS: We tested
      2233 consecutive CSF samples from 2162 patients. A positive PCR result was
      obtained in 143 patients, including 22 from the Oxford cohort. Logistic
      regression analysis of the Oxford cohort showed that fever, a virus-specific
      rash, and a CSF white-cell count of 5/microL or more were independent predictors
      of a positive PCR result. The likelihood ratio for a definite diagnosis of viral
      infection of the CNS in a patient with a positive PCR result, relative to a
      negative PCR result, was 88.2 (95% CI 20.6-378). The likelihood ratio for a
      possible diagnosis of viral infection of the CNS in a patient with a negative PCR
      result, relative to a positive PCR result, was 0.10 (0.03-0.39). INTERPRETATION:
      A patient with a positive PCR result was 88 times as likely to have a definite
      diagnosis of viral infection of the CNS as a patient with a negative PCR result.
      A negative PCR result can be used with moderate confidence to rule out a
      diagnosis of viral infection of the CNS. We believe that PCR will become the
      first-line diagnostic test for viral meningitis and encephalitis.

PMID- 9024375
TI  - Detection of antibodies to a putative hepatitis G virus envelope protein.
AB  - BACKGROUND: A flavivirus designated hepatitis G virus (HGV) has been isolated
      from the serum of patients with non-A-E hepatitis. Hitherto, the presence of HGV
      RNA in serum has been detected with the reverse transcription-polymerase chain
      reaction (RT-PCR) amplification method. We have now developed an immunoassay for
      antibodies against an HGV protein. METHODS: Recombinant HGV envelope protein E2
      was used as antigen in an ELISA. 80 blood donors, 99 intravenous-drug users, and
      11 patients with acute post-transfusion hepatitis were tested for antibodies to
      E2. The HGV-RNA status was assessed by RT-PCR. FINDINGS: Anti-E2 seroprevalence
      was 9% among the blood donors and 41% among the drug users; HGV-RNA prevalence
      was 2.5% and 38%, respectively. Whereas anti-E2 prevalence increased with the
      duration of drug use, HGV-RNA prevalence declined in parallel. In each group, the
      presence of anti-E2 and HGV RNA was almost mutually exclusive: none of the blood
      donors and only 4% of the drug users were positive for both markers at the same
      time. Of the 11 post-transfusion patients--who were all HGV-RNA positive and anti
      E2 negative at the onset of disease--four developed antibodies to E2 during the
      following year, and two of the four subsequently became HGV-RNA negative.
      INTERPRETATION: We conclude that a humoral immune response to E2 is associated
      with loss of detectable HGV viraemia. Thus, E2-specific antibodies might serve as
      a useful marker for diagnosing recovery from HGV infections. The immunoassay we
      describe should facilitate investigation of suspected infections and may be
      helpful in the elucidation of the clinical significance of HGV.

PMID- 9024376
TI  - Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic
      porphyria cutanea tarda.
AB  - BACKGROUND: Sporadic porphyria cutanea tarda is a skin disease associated with
      hepatic siderosis. Depletion of iron stores by phlebotomy is curative. The role
      of haemochromatosis genes in determining susceptibility to this disorder is
      controversial. We have examined the frequency in sporadic porphyria cutanea tarda
      of mutations (Cys282Tyr, His63Asp) in a novel MHC class-I-like gene, one of which
      (Cys282Tyr) is believed to cause haemochromatosis. METHODS: 41 patients with
      sporadic porphyria cutanea tarda, in whom the frequency of microsatellite alleles
      that define the ancestral haemochromatosis haplotype had previously been
      determined, and 101 healthy blood donors were studied for the presence of the
      Cys282Tyr and His63Asp mutations. We used restriction-enzyme digestion of PCR
      amplified genomic DNA. FINDINGS: The Cys282Tyr mutation occurred in 18 (44%) of
      patients compared with 11 (11%) of controls (relative risk 6.2, 95% CI 2.6-14.5,
      p = 0.00003). Seven (17%) patients, aged 48-79 years, were homozygotes. In 12
      patients, the Cys282Tyr mutation was associated with markers of the HLA-A3
      containing ancestral haemochromatosis haplotype. Ages at presentation were the
      same for those with or without the Cys282Tyr mutation. There was no difference in
      the frequency of the His63Asp mutation. INTERPRETATION: Inheritance of one or
      more haemochromatosis genes is an important susceptibility factor for sporadic
      porphyria cutanea tarda. Some homozygotes for the Cys282Tyr mutation present late
      in life with porphyria cutanea tarda, indicating that not all homozygotes present
      clinically with haemochromatosis. The relation between this genotype and disease
      needs further investigation.

PMID- 9024377
TI  - A 22-year-old with jaundice and a bit of a cough.

PMID- 9024378
TI  - Eliminating adult T-cell leukaemia cells with ultrasound.

PMID- 9024379
TI  - Screening test for coeliac disease.

PMID- 9024380
TI  - Human urethra transplants.

PMID- 9024381
TI  - Life-threatening interaction between clarithromycin and disopyramide.

PMID- 9024382
TI  - Plasma trade and the HIV epidemic.

PMID- 9024383
TI  - Adrenomedullin in pregnancy.

PMID- 9024384
TI  - Gene analysis in delta 4-3-oxosteroid 5 beta-reductase deficiency.

PMID- 9024386
TI  - Differing proteinuria control with cyclosporin and tacrolimus.

PMID- 9024385
TI  - Sensitivity of ligase chain reaction assay of urine from pregnant women for
      Chlamydia trachomatis.

PMID- 9024387
TI  - No news is good news at Washington AIDS meeting.

PMID- 9024388
TI  - Report charges "cover-up" by Canada's blood overseers.

PMID- 9024389
TI  - Hyperthyroidism.

PMID- 9024390
TI  - Aetiology of acute leukaemia.
AB  - Ionising radiation, in high dose and with acute exposure, is a factor that has
      been implicated in leukaemogenesis, but what is the evidence for leukaemogenesis
      and exposure to diagnostic X-rays, to natural terrestrial or cosmic ionising
      radiation, to electromagnetic fields, or to nuclear energy? Why is population
      mixing and infection a possible explanation for the clusters of childhood acute
      leukaemias around the nuclear processing plants of Sellafield and Dounreay? These
      questions, as well as how chemical agents, including therapeutic substances,
      might contribute to leukaemogenesis, are discussed in this last article in the
      leukaemia series.

PMID- 9024391
TI  - Are ethics and managed care strange bedfellows or a marriage made in heaven?

PMID- 9024392
TI  - Rapid self testing for HIV infection.

PMID- 9024393
TI  - CAPRIE trial.

PMID- 9024394
TI  - CAPRIE trial.

PMID- 9024395
TI  - CAPRIE trial.

PMID- 9024396
TI  - CAPRIE trial.

PMID- 9024397
TI  - CAPRIE trial.

PMID- 9024398
TI  - Screening for colorectal cancer.

PMID- 9024399
TI  - Screening for colorectal cancer.

PMID- 9024400
TI  - Screening for colorectal cancer.

PMID- 9024401
TI  - Screening for colorectal cancer.

PMID- 9024402
TI  - The Delta trial.

PMID- 9024403
TI  - Can tetanus boosting be rejected?

PMID- 9024404
TI  - The Manchester seaman.

PMID- 9024405
TI  - Inhibition of LDL oxidation by green tea extract.

PMID- 9024406
TI  - HIV vaccines.

PMID- 9024407
TI  - Low frequency of autoimmune disease in tropical Africa.

PMID- 9024408
TI  - Aspartame and brain cancer.

PMID- 9024409
TI  - Lowering of blood pressure and artery stiffness.

PMID- 9024410
TI  - Spinal cord stimulation for premature peripheral atherosclerosis.

PMID- 9024411
TI  - USA and shortage of food and medicine in Cuba.

PMID- 9024412
TI  - USA and shortage of food and medicine in Cuba.

PMID- 9024413
TI  - USA and shortage of food and medicine in Cuba.

PMID- 9024414
TI  - King George III and acute porphyria.

PMID- 9024415
TI  - CFC-free inhalers.

PMID- 9024416
TI  - A circus flea.

PMID- 9024417
TI  - Clinical relevance revisited.

PMID- 9024418
TI  - Sensitivity and reproducibility of the dual-mode actigraph under controlled
      levels of activity intensity.
AB  - The purpose of this study was to test the sensitivity and reproducibility of dual
      mode actigraphy as an objective measure of functional performance in healthy
      adults under controlled levels of activity intensity. Twenty subjects wore the
      instrument on the nondominant wrist while performing standardized tasks selected
      to represent day-to-day activities at three levels of intensity (five tasks in
      each level): light (1-2 metabolic equivalents), moderate (3-4 metabolic
      equivalents), and heavy (4-6 metabolic equivalents). Upon completion of each
      intensity level, subjects were asked to rate their level of exertion using Borg's
      15-point rating of perceived exertion (RPE) scale. Eighteen subjects repeated the
      protocol within 7 days. Zero-crossing and time-above-threshold modes successfully
      differentiated between light and moderate and between light and heavy activity.
      Reproducibility correlation coefficients (rs) across activity levels were .80 and
      .66 for the two modes, respectively. Results suggest dual-mode actigraphy may be
      useful for the study of performance variation and structure in healthy and
      chronically ill individuals.

PMID- 9024419
TI  - Immune responses to final exams in healthy and asthmatic adolescents.
AB  - Immune responses to an academic stressor were examined in healthy and asthmatic
      adolescents with regard to their illness symptom reports. Eighty-seven high
      school students completed a health diary for 2 weeks and provided three blood
      samples during midsemester, final-exam, and postexam periods. During exam week,
      all students showed significant immunological alterations from baseline. Natural
      killer cell activity was significantly lower, whereas lymphocyte proliferation
      and neutrophil superoxide release were significantly higher. These immune changes
      tended to return toward baseline during the postexam period, but the enhanced
      neutrophil reactivity continued to rise. Overall, immunological responses were
      similar between asthmatic subjects and controls. Appropriate medical management
      may have accounted for this similarity. However, subtle group differences in the
      postexam recovery pattern and a continuous activation of inflammatory cell
      function following a stressor may warrant further investigation.

PMID- 9024420
TI  - Weight, nutrition, and immune status in postpartal women.
AB  - Postpartal weight loss, nutritional intake, and immune status were examined in 65
      women. Although 80% of the women lost weight and were not overweight by the 4th
      postpartal month, the majority had diets that were inadequate in fat content (>
      or = 30% of calories from fat) or protein content (< or = 12% of calories from
      protein), or in terms of caloric intake (< or = 1,200 calories or > or = 2,200
      calories). Differences in some immune cell subsets were noted between women with
      high-fat and normal-fat diets. Women with high-fat diets had lower percentages of
      specific immune cell subsets than women with normal-fat diets. Protein intake was
      not related to immune cell phenotypes.

PMID- 9024421
TI  - An explanatory model of functional status in chronic obstructive pulmonary
      disease.
AB  - The purpose of this study was to test an explanatory model of variables
      influencing functional status in chronic obstructive pulmonary disease (COPD).
      The sample consisted of 104 patients with COPD (85 males, 19 females, mean age =
      65.5, SD = 7.7). The variables in the initial model were age, length of illness,
      pulmonary function, oxygen desaturation during exercise, dyspnea, depressed mood,
      anxiety, self-esteem, exercise capacity, and functional status. Path analysis
      revealed that exercise capacity (beta = .337, p = .0007), dyspnea (beta = .324, p
      = .0009), and depressed mood (beta = -.204, p = .011) directly influenced
      functional status Dyspnea (beta = .488, p < .0001), depression (beta = -.217, p =
      .003), and pulmonary function (beta = .421, p < .0001) indirectly influenced
      functional status through exercise capacity. Self-esteem (beta = -.492, p = .004)
      and anxiety (beta = .696, p < .0001) indirectly influenced functional status
      through depressed mood. The findings of this study suggest that efforts to
      improve functional status of individuals with COPD should focus on interventions
      that influence exercise capacity, dyspnea, anxiety, and depressed mood.

PMID- 9024422
TI  - Testing theoretical explanations of mammography use.
AB  - The theory of care-seeking behavior was tested in the context of mammography use
      among midwestern women (N = 178). In multivariate logistic regressions,
      mammography adherence in the past 5 years was related to habit, the interaction
      of anxiety and barriers, belief in one's risk of breast cancer, age, and family
      history of breast cancer. Recent use of mammograms (i.e., in the past 1 or 2
      years, depending on age) was related to norm and habit. Intention was related to
      utility beliefs regarding mammography, norm, habit, and belief in one's risk of
      breast cancer. As proposed from theory, anxiety and barriers interacted to
      influence adherence, the variables of habit, utility beliefs, and norm were
      related to either recent use or intention. Contrary to theory, belief in one's
      risk of breast cancer, age, and family history of breast cancer were related to
      adherence or intention after controlling for theoretically derived variables. The
      explanatory variables for each outcome were not identical, indicating that these
      mammography-related outcomes are characteristically different.

PMID- 9024423
TI  - Assessment of reliability and validity of the behavioral observation record for
      developmental care.
AB  - Due to time constraints, clinicians are rarely able to carry out neurobehavioral
      assessments that use the Naturalistic Observation of Newborn Behavior Instrument.
      The content validity, interrater reliability, and criterion-related validity for
      a less time-consuming instrument, the Modified Infant Behavioral Observation
      Record (MIBOR) for developmental care was evaluated in this study. Eight
      developmental care specialists evaluated the MIBOR for content validity. Fifteen
      infants (birth weight < 1,500 g) were observed to determine interrater
      reliability, and three were observed to evaluate criterion-related validity. The
      content validity of the MIBOR, as determined by average congruence, was 96.9%.
      Interrater reliability for each developmental care subsystem ranged from 67% to
      98%. Three of the four subsystems on the MIBOR achieved criterion-related
      validity, achieving an agreement of r = .60.

PMID- 9024424
TI  - From limbo to legitimacy: a theoretical model of the transition to the primary
      care nurse practitioner role.
AB  - The initial transitional year of professional practice is thought to provide the
      critical foundation on which new professionals build their expertise. The purpose
      of this study was to describe the experiences of new nurse practitioner graduates
      during their first year of primary care practice. Thirty-five persons were
      interviewed alone or in focus groups at approximately 1, 6, and 12 months after
      graduation. Grounded theory methodology guided the data collection and analysis.
      A theoretical model was constructed that represents the transition to the primary
      care nurse practitioner role. This model consists of a process called From Limbo
      to Legitimacy, which encompasses four major categories: Laying the Foundation,
      Launching, Meeting the Challenge, and Broadening the Perspective. Each category
      contains a set of subcategories that detail the multiple aspects of the
      experience. This model highlights both the distress and the accomplishments of
      the initial year of advanced practice.

PMID- 9024426
TI  - The effects of effleurage backrub on the physiological components of relaxation:
      a meta-analysis.

PMID- 9024425
TI  - Decentralization as a determinant of autonomy, job satisfaction, and
      organizational commitment among nurse managers.
AB  - The purpose of this study was to test a theoretical model of the following
      variables, decentralization, professional autonomy, job satisfaction, and
      organizational commitment. Data were collected through a comprehensive survey of
      first-line nurse managers (N = 200) in acute care hospitals with more than 100
      beds in British Columbia, Canada. The final model excluded all explored personal
      characteristics of the nurse manager-gender, health or vitality status, marital
      status, age, education, and years of supervisory or management experience. Job
      satisfaction was found to be an important predictor of organizational commitment.
      However, decentralization was most important because it affected organizational
      commitment directly, as well as indirectly, through professional autonomy and job
      satisfaction.

PMID- 9024427
TI  - Biology of the rotator cuff tendon.
AB  - Tendons are complex composite material composed primarily of water, collagen,
      proteolycans, and cells, designed to transmit tensile loads from muscle to bone.
      Although rotator cuff tendons differ in many ways from other tendons in the body,
      a knowledge of basic tendon structure and function is helpful in understanding
      rotator cuff tendon biology, injury, and repair. In addition to type I collagen,
      rotator cuff tendons contain small amounts of type III collagen, which play a
      role in healing and repair. In comparison with other tendons, the increased
      glycosaminoglycan and proteoglycan content seen in rotator cuff tendons may be
      adaptive, pathologic, or both. The etiology of rotator cuff pathology is probably
      related to trauma, aging, and degeneration. As our understanding of these
      processes increases, we will be able to develop and implement improved
      preventative and therapeutic interventions for rotator cuff pathology.

PMID- 9024428
TI  - Biomechanics of the rotator cuff.
AB  - Thorough understanding of rotator cuff mechanics is important for effective
      treatment and/or prevention of cuff injuries. This understanding is achieved
      through knowledge of normal cuff structure and mechanics. Only then, can the
      effects of injuries and pathologic processes on normal cuff function be carefuly
      assessed. Rotator cuff structures are viewed and analyzed on a number of
      different levels. This article presents current knowledge of rotator cuff
      mechanics through review of cuff structure and anatomy, corocoacromial arch
      structure and biomechanics, and biomechanical models.

PMID- 9024429
TI  - Pathology of failure of the rotator cuff tendon.
AB  - In failure of the rotator cuff tendon, interference with its function prevents
      the rotator cuff from fulfilling its physiologic role. Trauma in younger
      individuals, calcifying tendinitis, degenerative changes of cuff tendon, and
      partial- or full-thickness tears cause cuff failure intrinsically. Degenerative
      changes constitute the most frequent cause of cuff failures and correlate with
      tendon tearing. An acromial spur, long coracoid process, subacromial bursitis,
      and thickening of the corocoaromial ligament causes cuff failure extrinsically.

PMID- 9024430
TI  - Rotator cuff evaluation: imaging and diagnosis.
AB  - A variety of disorders can lead to disease and pathology of the rotator cuff
      tendons. The most important information is obtained during a careful history and
      physical examination. With the judicious use of various diagnostic modalities,
      evaluation of the cause of the rotator cuff disease is possible.

PMID- 9024431
TI  - Nonoperative management of full-thickness tears of the rotator cuff.
AB  - Rotator cuff tendonopathies are among the most common disorders encountered in
      the shoulder. There is an abundance of literature on the operative management of
      these lesions, but only a small amount devoted to nonoperative treatment of full
      thickness tears of the rotator cuff. The purpose of this article is to review the
      literature pertaining to full-thickness tears as well as our results with
      expectant management.

PMID- 9024432
TI  - Special considerations in the athletic throwing shoulder.
AB  - Overhead athletes are susceptible to a number of shoulder problems due to the
      repetitive nature and force needed to perform at a competitive level. Frequently,
      the rotator cuff becomes injured due to primary or secondary impingement. In
      young athletes, subtle instability is often the cause of rotator cuff tendinitis,
      but will frequently respond to a coordinated rehabilitation program. Older
      athletes are more likely to have rotator cuff injuries due to anatomic changes in
      the coracoacromial arch. This article outlines the mechanism of injury to the
      rotator cuff and our approach in dealing with shoulder problems in the overhead
      athlete.

PMID- 9024433
TI  - Arthroscopic debridement and acromioplasty versus mini-open repair in the
      management of significant partial-thickness tears of the rotator cuff.
AB  - Treatment options for partial-thickness rotator cuff tears have included
      debridement and acromioplasty or open repair. The outcome of these two treatments
      has been difficult to assess from the literature. The results of a retrospective
      review of arthroscopic versus open treatment are reviewed with recommendations
      for a treatment algorithm.

PMID- 9024434
TI  - Full-thickness tears: arthroscopic repair.
AB  - Arthroscopic repair of rotator cuff tears is an option for a surgeon with
      advanced arthroscopic skills and a thorough knowledge of open repair technique.
      Surgical indications and a detailed description of operative technique are
      presented. Arthroscopic rotator cuff repair offers theoretical advantages over
      open repair, but long-term studies are needed to demonstrate its effectiveness.

PMID- 9024435
TI  - Single-tendon tears of the rotator cuff. Evaluation and treatment of
      subscapularis tears and principles of treatment for supraspinatus tears.
AB  - Successful surgical treatment of single-tendon tears, which involve the
      supraspinatus or the subscapularis requires careful attention to technical
      details. In supraspinatus tears, careful mobilization and secure repair of the
      tendon will usually give a good outcome. In subscapularis tears, the diagnosis is
      not difficult if one carefully evaluates the patient for the classic
      pathognomonic findings of such a tear. If the tear is confirmed by CT or MR
      imaging and an acute repair is performed, the outcome is usually satisfactory.

PMID- 9024436
TI  - Massive rotator cuff tears: debridement versus repair.
AB  - In many studies, short-term and midterm results of debridement seem to show
      satisfactory results. However, the three long-term studies currently available
      all report that these initial results deteriorate significantly with time and are
      not acceptable. If debridement is considered, careful preoperative and
      intraoperative evaluation as discussed by Burkhart should be followed. We believe
      an adequate understanding of the anatomic subtleties, pathologic changes,
      biomechanical forces, and advanced reconstructive techniques allows repair to be
      performed in most, if not all, rotator cuff tears of the shoulder. The findings
      of the study described herein indicate that repair of these tears is the
      treatment of choice.

PMID- 9024437
TI  - Partial repair of massive rotator cuff tears: the evolution of a concept.
AB  - Partial repair of massive rotator cuff tears has eliminated the need for tendon
      transfers to close large defects. Side-to-side repair is usually done as a first
      step, with the margins of the tear then repaired to bone. Side-to-side repair
      causes a "margin convenience" toward the greater tuberosity, enhancing the
      mechanics of the construct by decreasing the strain at the free margin of the
      rotator cuff tear. By combining tendon-to-tendon repair with the tendon-to-bone
      repair, the surgeon can create a functional rotator cuff in most patients with
      massive tears.

PMID- 9024438
TI  - Hospital and patient characteristics associated with variation in 28-day
      mortality rates for very low birth weight infants. Vermont Oxford Network.
AB  - BACKGROUND: The outcomes for very low birth weight infants vary among neonatal
      intensive care units (NICUs), but the reasons for this variation are not well
      understood. We used the database of a large neonatology research network to
      determine whether either admission characteristics of the infants or specific
      characteristics of the units such as annual patient volume and the presence of a
      pediatric residency program could account for observed differences in neonatal
      mortality rates among units. METHODS: We studied 7672 infants with birth weights
      from 501 to 1500 g treated during 1991 and 1992 at 62 NICUs participating in the
      Vermont Oxford Network Database. RESULTS: Overall, 14.7% of the study infants
      died within 28 days of birth (interquartile range 9.9% to 18.1%). The ratio of
      the number of observed deaths at an NICU to the number of deaths predicted based
      on the characteristics of infants treated at the NICU (standardized neonatal
      mortality ratio, [SNMR]) varied significantly among units (range 0 to 1.69, z =
      4.24). There was no association between annual patient volume and either
      mortality rate (r = .17) or SNMR (r = .22). Observed mortality rates (17% vs 13%)
      and SNMR (1.04 vs .87) were both higher at the 24 hospitals with pediatric
      residency training programs than at the 38 hospitals without such programs.
      Hospitals with residency programs had higher average annual patient volumes (104
      vs 66). In an analysis simultaneously adjusting for patient characteristics,
      volume, and presence of a residency program, neither volume (odds ratio [OR] per
      10 additional cases treated 1.01, 95% confidence interval [CI], .98 to 1.04) nor
      presence of a pediatric residency program (OR 1.18, 95% CI, .94 to 1.47) was
      significantly associated with neonatal mortality risk. CONCLUSION: There are
      differences in neonatal mortality rates among NICUs that cannot be explained by
      differences in the measured admission characteristics of the infants, suggesting
      that the effectiveness of medical care varies among units. Neither the annual
      volume of very low birth weight infants treated in a unit nor the presence of a
      pediatric residency training program was independently associated with neonatal
      mortality rates for very low birth weight infants.

PMID- 9024439
TI  - Improving care for minority children with asthma: professional education in
      public health clinics.
AB  - OBJECTIVE: Recent studies have shown that lack of continuing primary care for
      asthma is associated with increased levels of morbidity in low-income minority
      children. Although effective preventive therapy is available, many African
      American and Latino children receive episodic treatment for asthma that does not
      follow current guidelines for care. To see if access, continuity, and quality of
      care could be improved in pediatric clinics serving low-income children in New
      York City, we trained staff in New York City Bureau of Child Health clinics to
      provide continuing, preventive care for asthma. METHODS: We evaluated the impact
      of the intervention over a 2-year period in a controlled study of 22 clinics.
      Training for intervention clinic staff was based on National Asthma Education and
      Prevention Program guidelines for the diagnosis and management of asthma, and
      included screening to identify new cases and health education to improve family
      management. The intervention included strong administrative support by the Bureau
      of Child Health to promote staff behavior change. We hypothesized that after the
      intervention, clinics that received the intervention would, compared with control
      clinics, have increased numbers of children with asthma receiving continuing care
      in the clinics and increased staff use of new pharmacologic and educational
      treatment methods. RESULTS: In both the first and second follow-up years, the
      intervention clinics had greater positive changes than control clinics on
      measures of access, continuity, and quality of care. For second year follow-up
      data these include: for access, greater rate of new asthma patients (40/1000 vs
      16/1000; P < .01); for continuity, greater percentage of asthma patients
      returning for treatment 2 years in a row (42% vs 12%; P < .001) and greater
      annual frequency of scheduled visits for asthma per patient (1.85 vs .88; P <
      .001); and for quality, greater percentage of patients receiving inhaled beta
      agonists (52% vs 15%; P < .001) and inhaled antiinflammatory drugs (25% vs 2%; P
      < .001), and greater percentages of parents who reported receiving patient
      education on 12 topics from Bureau of Child Health physicians (71% vs 58%; P <
      .01) and nurses (61% vs 44%; P < .05). CONCLUSION: We conclude that the
      intervention substantially increased the Bureau of Child Health staff's ability
      to identify children with asthma, involve them in continuing care, and provide
      them with state-of-the-art care for asthma.

PMID- 9024440
TI  - Children and adult perceptions of childhood asthma.
AB  - OBJECTIVE: To explore children's and parents' assessment of children's asthma.
      DESIGN: Prospective 2-month cohort study in which children and parents were
      reviewed at baseline and 1-month intervals. SETTING: Mid-sized, English-speaking,
      industrial community serving an urban and regional rural population. PATIENTS OR
      PARTICIPANTS: Fifty-two children, 7 to 17 years old, with a wide range of asthma
      severity, and their parents. INTERVENTIONS: We offered patients with inadequately
      controlled asthma additional inhaled steroid. MAIN OUTCOME MEASURES: Children and
      parents provided global ratings of change in childhood symptoms and children
      completed spirometry and the Paediatric Asthma Quality of Life Questionnaire at
      clinic visits. Patients recorded peak flow rates, symptoms, and medication use in
      a daily diary. The diary symptom report, medication use, and spirometry were
      combined to form an asthma control score. RESULTS: In children younger than 11,
      children's global rating of change in symptoms correlated strongly with changes
      in quality of life (0.54 to .67) but not with measures of airway caliber or
      asthma control, while parents' global ratings did not correlate with children's
      quality of life but showed moderate correlations with airway caliber (0.29 to
      .48) and asthma control (0.50). In children over the age of 11, correlations with
      all clinical variables were higher for their own than their parents' global
      ratings. CONCLUSIONS: In children under 11, clinicians can gain complementary
      information from questioning children and parents. For children over 11, parents
      can provide little if any information beyond that obtained through questioning
      the child.

PMID- 9024441
TI  - Prevention of pediatric drowning and near-drowning: a survey of members of the
      American Academy of Pediatrics.
AB  - OBJECTIVE: To assess pediatricians' knowledge about the epidemiology of childhood
      drowning, their opinions and current practices regarding its prevention, and
      their interest in taking on more responsibility for its prevention. DESIGN: A
      self-administered questionnaire was mailed to 800 pediatricians in the United
      States, randomly selected from the American Academy of Pediatrics' approximately
      18,000 full fellows. RESULTS: A total of 560 completed surveys were returned, a
      response rate of 70.1%. Although 85% of respondents believe it is the
      responsibility of pediatricians to become involved in community and/or
      legislative efforts to prevent childhood drowning, only 4.1% were involved in
      such efforts. Only a minority of respondents provided written materials and
      anticipatory guidance on drowning prevention to their patients. Women were more
      likely than men to discuss drowning prevention with their patients. Younger
      physicians were more likely than older physicians to discuss drowning prevention
      with their patients. Physicians who received formal education on drowning
      prevention during their pediatric residency training were more likely to provide
      written materials and anticipatory guidance on drowning prevention to their
      patients. However, only 17.9% of respondents received formal education on
      drowning prevention during their pediatric residency training. Seventy-four
      percent of all respondents felt that further education on the prevention of
      childhood drowning and near-drowning would be useful to them. CONCLUSION:
      Although drowning is the second leading cause of death by unintentional injury in
      the pediatric population (aged 0 to 19 years), most pediatricians do not
      routinely provide information to their patients, or to their patients' parents,
      on drowning prevention. IMPLICATION: Pediatricians have been effective child
      advocates in many areas of injury prevention. If the prevention of drowning is
      made a priority in pediatric practice, many more children's lives will be saved.

PMID- 9024442
TI  - Comparison of inpatient charges between academic and nonacademic services in a
      children's hospital.
AB  - OBJECTIVE: To compare inpatient hospital charges generated within a children's
      hospital by academic and nonacademic pediatric services for common medical
      diagnoses. METHODS: Hospital admissions to a free-standing children's hospital
      between 9/1/90 and 8/30/94 were selected for patients who were hospitalized 1 to
      14 days, with one of six selected diagnoses, and with discharge attending of
      record either a private pediatrician or an academic subspecialist. Discharge
      diagnoses, based on ICD-9 codes, included asthma (n = 1983), bronchiolitis (n =
      692), gastroenteritis (n = 733), rule out sepsis (n = 1065), urinary tract
      infection (n = 516), and viral meningitis (n = 288). Charges associated with
      patient records were dichotomized as above or below the median charge for each
      diagnostic category. Each category was analyzed separately using a logistic
      regression model where the dichotomous-dependent variable was charges above the
      median charge for each diagnosis. Independent variables included physician type,
      payor status, patient residence, ICD-9 code as primary or secondary diagnosis,
      patient age, and presence of complicating conditions. RESULTS: By univariate
      comparison, academic physicians cared for a higher percentage of underinsured
      patients, and their care was more expensive. Complicated claims were associated
      with higher charges than uncomplicated claims for all diagnostic categories.
      Academic and nonacademic physicians were equally likely to generate above-median
      charges for five of the six diagnostic categories when controlling for
      confounding factors. A linear regression model in which charge was the dependent
      variable generated similar results. CONCLUSIONS: Within the same pediatric health
      care facility, no consistent difference was found between charges incurred on
      academic vs private inpatient services.

PMID- 9024443
TI  - Diagnosis and management of posterior plagiocephaly.
AB  - OBJECTIVE: The management of infants with posterior plagiocephaly has been
      controversial both because of widely differing estimates in the literature of the
      relative frequencies of true lambdoidal synostosis vs positional molding and
      because of divergent approaches to treating this problem in different
      institutions. Based on our experience, we hypothesized that the vast majority of
      children with posterior plagiocephaly did not have true synostosis and that the
      cosmetic impairment in such patients could be effectively treated with
      nonsurgical modalities. METHODS: Between 1992 and 1995, we prospectively applied
      in 71 infants a consistent management philosophy for these malformations that has
      incorporated a detailed evaluation of sutural anatomy as the basis for a
      physiologic approach to treatment. This approach has been directed at
      distinguishing true synostosis from deformational plagiocephaly and at avoiding
      surgery for patients with deformational abnormalities by using a combination of
      nonsurgical modalities to restore normal cranial growth dynamics. All children
      first underwent skull radiographs to determine whether the lambdoidal sutures
      were patent. In equivocal cases, computed tomography was also performed. Patients
      without true synostosis were enrolled on a course of positional therapy. In
      patients that did not improve after 2 to 3 months, a custom-fitted orthoplastic
      molding helmet was applied to facilitate passive skull recontouring. RESULTS:
      Forty children had patent sutures based on skull radiographs, and 29 others, in
      whom the radiographs were equivocal, had open sutures based on computed
      tomography, thus establishing the diagnosis of deformational plagiocephaly in 69.
      Predisposing factors for this deformity included a strong positioning preference
      during early infancy (n = 67), torticollis (n = 10), prematurity (n = 6), and
      developmental delay (n = 2). Only two patients had true lambdoidal synostosis; in
      each case, this was associated with synostosis of the posterior sagittal suture
      and was managed effectively with cranial reconstructive surgery. Thirty-five
      patients with deformational plagiocephaly had a dramatic improvement in their
      cranial contour with positional therapy alone; 34 patients failed to improve and
      were treated with molding helmets. All but five children, each of whom was more
      than 6 months old at initial intervention (P < .025), developed a normal or
      nearly normal head shape with these measures. CONCLUSION: The vast majority of
      children with posterior plagiocephaly do not have true synostosis and can be
      effectively managed by nonsurgical means. The impact of positional preference on
      the development of this process is discussed.

PMID- 9024444
TI  - Response to battered mothers in the pediatric emergency department: a call for an
      interdisciplinary approach to family violence.
AB  - BACKGROUND: Child abuse and wife abuse are linked. Studies indicate 30% to 59% of
      mothers of children reported for child abuse also are battered. In homes where
      domestic violence occurs, the children are at increased risk of physical abuse or
      neglect. Children who witness battering of their mothers are at risk for
      psychosocial sequelae including developmental delays and posttraumatic stress
      disorder. OBJECTIVE: To determine pediatric emergency medicine fellows' level of
      preparedness to respond to battered mothers, and to assess obstacles and
      attitudinal barriers to their effective response. STUDY DESIGN: Self-reported
      written survey. METHODS: A 30-item anonymous questionnaire was mailed to 162
      pediatric emergency medicine fellows in the United States and Canada in 1995. A
      response rate of 77.2% (n = 125) was achieved. RESULTS: Before fellowship, 97.6%
      of respondents had training (including formal courses, conferences, and direct
      patient contact) on child abuse/neglect although only 29.6% received similar
      instruction on woman battering. There was a marked disparity between patient
      contact experience for child abuse/neglect and woman battering throughout
      training. Before fellowship, 89/122 (73%) reported direct involvement in at least
      10 cases of child abuse/neglect. Seventy-one (57.3%) of 124 fellows had not
      handled any cases of woman battering before fellowship; 106/124 (85.5%) had been
      directly involved in fewer than 10 cases. During fellowship 81 (67.5%) of 120
      respondents had been involved in at least 10 cases of child abuse/neglect and
      46/120 (38.3%) had handled at least 20 cases. In contrast, 72 (73.5%) of the 98
      responding fellows had not handled any cases of woman battering during
      fellowship. Furthermore, 86/100 fellows reported no formal training on woman
      battering in their fellowship curricula. Only 5/118 (4.2%) reported having
      protocols in place for responding to battered women in the pediatric emergency
      department. Items most frequently selected from a list of potential obstacles to
      responding to battered women included: lack of a protocol (82/113), lack of
      formal training in the field (103/118), and lack of experience with woman
      battering cases (100/117). The majority, 75/118 (63.6%), believed that responding
      to battered mothers did not belong in the preview of pediatrics. Potential
      attitudinal barriers confirmed with the greatest frequency included: frustration
      that nothing could be done and lack of time to respond appropriately to battered
      mothers in the pediatric emergency department. CONCLUSIONS: Battered mothers are
      rarely identified in the pediatric emergency department even though the
      physicians report handling a significant number of child abuse/neglect cases.
      Education on domestic violence, including the implications of woman battering for
      childrens' health, should be incorporated in the training curricula of pediatric
      emergency department physicians to raise awareness of the need to explore for the
      presence of concurrent abuse in both children and their mothers. Identifying
      battered women through their children will impact greatly on the welfare of both
      mother and child.

PMID- 9024445
TI  - Long-term appearance of lacerations repaired using a tissue adhesive.
AB  - BACKGROUND: Histoacryl Blue (HAB), a tissue adhesive, has been shown to decrease
      laceration repair time, cause less pain to the child, eliminate the need for
      suture removal, and result in a similar short-term cosmetic outcome compared with
      conventional suturing. Reports suggest that poor correlation can exist between
      the short-term and long-term cosmetic outcomes for lacerations repaired by
      conventional suturing. Therefore, this study compares the long-term cosmetic
      outcome of HAB to conventional suturing for laceration repair in children.
      DESIGN: Prospective, randomized clinical trial. PARTICIPANTS: Children presenting
      an urban pediatric emergency department for laceration repair between October
      1994 and February 1995 were eligible. Patients less than 1 or more than 18 years
      old, those with lacerations more than 5 cm in length, or in areas of high tension
      or mobility were excluded. INTERVENTIONS: After routine wound management,
      including subcutaneous closure when deemed necessary, patients were randomized to
      receive skin sutures or HAB for cutaneous closure. Photographs taken at the 2
      month and 1-year follow-up visits were evaluated for cosmetic appearance by two
      plastic surgeons blinded to the method of repair. RESULTS: Sixty-one children
      were enrolled: HAB (N = 30), suture (N = 31). Thirty HAB and 25 sutured patients
      were assessed at 2 months, while 17 HAB and 15 sutured patients were reevaluated
      at 1 year. Patients that followed-up at 2 months and 1 year were comparable to
      those with no follow-up in: treatment group (HAB vs suture), demographics, wound
      characteristics, and initial parental satisfaction. The two plastic surgeons
      graded the cosmetic appearance of the wounds repaired by HAB to be comparable to
      those repaired by conventional suturing at both the 2-month and 1-year follow-up.
      CONCLUSIONS: The use of HAB is an ideal alternative to conventional suturing for
      the cutaneous closure of low tension lacerations in children with a long-term
      cosmetic outcome comparable to conventional suturing.

PMID- 9024446
TI  - Hospital services for rural children in Washington State.
AB  - OBJECTIVE: To examine the current delivery of inpatient hospital services to a
      statewide population of rural children, define the types of pediatric conditions
      currently treated in rural hospitals or transferred to urban centers, and explore
      the role of rural pediatricians and family practitioners in the care of children
      in rural hospitals. DESIGN: Retrospective review of statewide hospital discharge
      data. SUBJECTS: All patients younger than 18 years of age with nonsurgical
      diagnoses discharged from both urban and rural civilian hospitals in Washington
      State during 1989 and 1990. RESULTS: Of 69690 pediatric hospital discharges
      during the study period, 16% were rural residents and 10% were from rural
      hospitals. Rural hospitals cared for 59% of hospitalized rural children. Marked
      differences were found between urban and rural hospitals in the diagnoses
      treated; more than two-thirds of all discharges for chemotherapy, psychiatric
      disorders, and neonates with multiple major problems were from urban hospitals;
      but the majority of the discharges for gastrointestinal diagnoses, respiratory
      conditions, or minor problems in the neonatal period were from rural hospitals.
      Rural hospitals with staff pediatricians had higher annual pediatric discharges,
      total charges, lengths of stay, and case mix with a higher proportion of neonates
      with complications, compared to hospitals without pediatricians. However, there
      was no evidence that these hospitals served as local referral centers for rural
      pediatric inpatients; the proportion of patients from outside the local hospital
      catchment areas was similar for rural hospitals with staff pediatricians and for
      those without. In rural hospitals, pediatricians and family practitioners were
      listed as the attending physician for 37% and 49% of discharges, respectively.
      The average rural pediatrician cared for five times as many inpatients as a rural
      family practitioner. Pediatricians cared for significantly more neonates with
      birth weights of less than 2500 grams, but otherwise had a similar case mix among
      inpatient discharges as rural family practitioners. CONCLUSIONS: Most rural
      children in Washington who require hospitalization for common problems receive
      their care in local rural hospitals staffed with pediatricians and family
      practitioners, although those with illnesses requiring a high level of specialty
      care are predominantly cared for in urban centers. Rural pediatricians make a
      substantial contribution to the care of rural children, especially in the area of
      neonatal care, although their presence in rural hospitals does not in itself
      create local referral centers. Inpatient volumes are higher for pediatricians,
      but their case mix is similar to that of rural family practitioners, except in
      the area of neonatology. These data support the recommendations that family
      practitioners contemplating rural practice receive training in general inpatient
      pediatrics (regardless of whether they are going to a site with pediatricians)
      and that pediatricians in rural practice be trained for a high volume of
      inpatient cases, including problems of low birth weight infants. Because systems
      of hospital care for rural children depend on regionalized programs, clinical and
      educational linkages between urban centers and rural providers should be
      developed and supported.

PMID- 9024447
TI  - How fetal cocaine exposure increases neonatal hospital costs.
AB  - OBJECTIVE: Our goals were to document hospital costs associated with prenatal
      cocaine exposure in an understudied population-women using rural county public
      health units who had minimal access to drug rehabilitation and whose cocaine of
      choice was crack with little other illicit drug use- and to explore why increased
      costs occur in an effort to identify cost-reduction strategies. METHODS: We
      identified a sample of cocaine-exposed infants who were computer-matched to a
      control group with no history or evidence of cocaine exposure. Matching was
      performed one-to-one on the variables of maternal race, age, parity, time of
      entry into prenatal care, and alcohol and nicotine use. There were 327 live
      births, for whom 311 were correctly classified as to their prenatal cocaine use
      and had billing and medical records available for review (156 exposed, 155
      nonexposed). RESULTS: Hospital charges were positively correlated with length of
      stay. Cocaine-exposed infants had an across-the-board increase in utilization of
      hospital resources as well as higher hospital charges and longer lengths of stay.
      Cocaine-exposed infants were significantly younger in gestational age and lower
      in birth weight. Significantly more cocaine-exposed infants were admitted to the
      neonatal intensive care unit, had more social and family problems delaying
      discharge, and received more septic work-ups. In addition, of those infants urine
      screened for cocaine at delivery, 92% were screened secondary to a maternal
      history of prenatal use. CONCLUSIONS: Cost-reduction strategies should be aimed
      at measures that reduce length of stay by addressing problems identified
      prenatally as an outpatient before delivery and by influencing objective decision
      making regarding the need for medical interventions with the infant after birth.

PMID- 9024448
TI  - The influence of provider behavior, parental characteristics, and a public policy
      initiative on the immunization status of children followed by private
      pediatricians: a study from Pediatric Research in Office Settings.
AB  - OBJECTIVES: To determine the relative impact of parental characteristics,
      provider behavior, and the provision of free vaccines through state-sponsored
      vaccine volume programs (VVPs) on the immunization status of children followed by
      private pediatricians. STUDY DESIGN: Retrospective and cross-sectional surveys of
      immunization data. SETTING: The offices of 15 private pediatricians, from 11
      states, who were members of the Pediatric Research in Office Settings network.
      Seven of these physicians used vaccines provided through VVPs. PATIENTS: Children
      2 to 3 years old followed by the participating physicians. METHODS: The
      immunization status of children was assessed from two separate samples. For
      sample 1, immunization data were abstracted from the medical records of 60
      consecutive eligible children seen in each office. Parents of the selected
      children indicated the method of payment for immunizations and the education
      levels of the mothers. Because this cross-sectional survey might have oversampled
      frequent health care users, a retrospective chart review of up to 75 randomly
      selected children in each pediatrician's practice was also conducted (sample 2).
      Additional data were collected from the parents of children in sample 2 by
      telephone interviews. For both samples, patients were considered to be fully
      immunized if they had received four diphtheria-tetanus-pertussis/diphtheria
      tetanus vaccines, three oral poliovirus/inactivated poliovirus vaccines, and one
      measles-mumps-rubella vaccine before their second birthdays. Before collecting
      vaccination data, pediatricians completed a survey detailing their immunization
      beliefs and practices. Logistic regression was used to identify factors that were
      independently associated with a child being fully immunized. RESULTS: For sample
      1, 81.7% of the 857 children surveyed were fully immunized. Practitioner-specific
      immunization rates varied widely, ranging from 51% to 97%. The immunization rate
      of children who received vaccines provided by VVPs was similar to that of
      children whose immunizations were not provided by VVPs (81.2% vs 82.2%; odds
      ratio [OR] for a VVP as a predictor for being fully immunized, 0.94, 95%
      confidence interval [CI], 0.66 to 1.32). In addition, parents who paid for
      immunizations out of pocket were as likely to have fully immunized children as
      those who had little or no out-of-pocket expenditures for vaccines (OR, 1.13; 95%
      CI, 0.75 to 1.13). In the logistic model, only individual pediatrician and size
      of the metropolitan area in which the pediatrician's practice was located were
      significant predictors of a child's immunization status. The results from sample
      2 were similar; 82.1% of the 772 surveyed patients were fully immunized. With
      sample 2, individual pediatrician and age of the child at the time of the survey
      were the only predictors of immunization status. The OR of a VVP as a predictor
      of a child being fully immunized was 1.37 (95% CI, 0.65 to 2.90). CONCLUSIONS:
      Individual provider behavior may be the most important determinant of the
      immunization status of children followed by private pediatricians. In our
      samples, the effect of parental characteristics was limited. State-sponsored VVPs
      were not associated with higher immunization rates, perhaps because cost of
      vaccines did not seem to be a significant barrier to immunization in this
      population.

PMID- 9024449
TI  - C-reactive protein is a useful marker for guiding duration of antibiotic therapy
      in suspected neonatal bacterial infection.
AB  - OBJECTIVE: To determine whether C-reactive protein (CRP) can be used as a
      parameter to identify the time point when antibiotic treatment can safely be
      discontinued in a defined major subgroup of neonates treated for suspected
      bacterial infection. PATIENTS: One hundred seventy-six newborns with birth
      weights of greater than 1500 g and without central lines and mechanical
      ventilation who had suspected bacterial infection were enrolled in a prospective
      study. SETTING: Tertiary care neonatal reference center. DESIGN: Serum
      concentrations of CRP were determined 24 to 48 hours after the first dose of
      antibiotics. If CRP levels were less than 10 mg/L, infants were considered
      unlikely to be infected, and the antibiotic treatment was stopped using CRP as
      the single decision criterion in 84 of 94 newborns (group 1). Infants with CRP
      levels of 10 mg/L or greater were considered likely to be infected and randomized
      to two study groups. In 38 of 39 neonates (group 2a), CRP was determined daily,
      and antibiotic therapy was discontinued as soon as CRP returned to less than 10
      mg/L. Forty-three neonates with likely infection (group 2b) were treated for at
      least 5 days, and relapse rates of bacterial infections were compared between
      groups 2a and 2b. OUTCOME MEASURES: The primary outcome variable of the study was
      the number of infectious relapses of the primary infection. This was assessed by
      the need for a second course of antibiotics within 4 weeks of the first one. The
      value of CRP for guiding treatment duration was determined by calculating the
      negative predictive value of CRP with respect to further treatment in study
      groups 1 and 2a. Treatment durations and relapse incidence in the two groups of
      neonates with likely infection (groups 2a and 2b) were compared. RESULTS: Within
      the 4-week follow-up period, one infant in group 1 and no infant in group 2a
      received a second course of antibiotics for bacterial infection. CRP levels of
      less than 10 mg/L determined later than 24 hours after beginning the antibiotic
      treatment thus correctly identified 120 of 121 infants as not needing further
      antibiotics. This corresponds to a negative predictive value with respect to
      further treatment of 99% (95% confidence interval, 95.4% to 99.9%). The mean
      treatment duration was 3.7 (median, 4; range, 3 to 6) days in the CRP-guided
      group and 5.5 (median, 5; range, 5 to 7) days in the at least 5-day study group.
      In the latter group, one infant was treated for a potential relapse, and one
      infant was treated for a likely relapse. The low relapse rates in both treatment
      groups are a preliminary indication that relapses may not occur more frequently
      if patients are treated until CRP is negative rather than for a 5-day or longer
      treatment period. CONCLUSIONS: We conclude that CRP could be a key parameter for
      individually guiding the duration of antibiotic treatment in a major subgroup of
      newborns with suspected bacterial infection. This approach would allow
      considerably shorter courses of antibiotic therapy.

PMID- 9024450
TI  - Pilot interferon-beta trial in children with chronic hepatitis B who had
      previously not responded to interferon-alpha therapy.
AB  - BACKGROUND: Recombinant interferon alpha (IFN-alpha) treatment is useful in 40%
      of children with chronic hepatitis B. However, nonresponder children continue to
      have viral replication and a progressive disease. OBJECTIVE: To administer
      natural IFN-beta to hepatitis B virus chronic carrier children who had not
      responded to a previous IFN-alpha cycle. METHODS: Twenty-two children with
      chronic hepatitis B, nonresponders to a previous IFN-alpha cycle, were retreated
      with 5 MU/m2 of body surface of natural IFN-beta, administered intramuscularly,
      three times per week for 24 weeks. RESULTS: At the end of treatment, 9 (41%) of
      22 children became hepatitis B virus DNA negative. Hepatitis B e antibodies (anti
      HBe) developed in 5 of these children, and 6 had normal alanine aminotransferase
      values. At the end of the posttreatment follow-up (21 months from the beginning
      of the study), 10 (45%) of 22 children were viral DNA negative, 7 (32%) of 22
      were anti-HBe positive (none of them had viral DNA in serum), and 11 (50%) of 22
      had normal alanine aminotransferase levels (10 without detectable viral DNA and 7
      anti-HBe positive). CONCLUSION: IFN-beta seems to be an effective retreatment
      therapy for children with chronic hepatitis B who are nonresponders to a first
      IFN-alpha cycle; however, a controlled study should be performed to confirm these
      results.

PMID- 9024451
TI  - Effect of corticosteroids on intracranial pressure, computed tomographic
      findings, and clinical outcome in young children with tuberculous meningitis.
AB  - OBJECTIVE: To study the effect of highdose prednisone on intracranial pressure
      (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young
      children with moderate to severe tuberculous meningitis (TBM). STUDY DESIGN:
      Prospective, controlled, randomized study. METHODS: Continuous lumbar,
      cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed
      in 141 consecutive children with TBM at admission. All children were then
      randomly allocated to a nonsteroid group (71 children) or a steroid group (70
      children) who received prednisone (first 16 children, 2 mg/kg per day; next 54
      children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and
      CT scanning were repeated regularly, and clinical outcome was assessed after 6
      months of antituberculosis treatment. RESULTS: No statistically significant
      difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was
      found between the steroid and nonsteroid groups after the first month of
      treatment. Basal ganglia infarcts developed in 16% of children in the steroid
      group and 24% in the nonsteroid group during the first month of treatment.
      Neither this incidence nor the eventual size of infarcts present at admission
      differed significantly between the two treatment groups. Single or multiple
      tuberculomas were seen on the first CT scans of 7 children (5%), whereas
      tuberculomas developed in 11 children (8%) at treatment. Both the response of the
      tuberculomas to treatment and the incidence of new tuberculomas were
      significantly improved by steroid therapy. Basal enhancement was also
      significantly less in the steroid group after 1 month of treatment. Steroids
      lowered mortality in stage III TBM significantly. Similarly, more surviving
      children in the steroid group had IQs of greater than 75 than did the those in
      the nonsteroid group. No significant difference was found in the incidence of
      motor deficit, blindness, or deafness. CONCLUSIONS: Corticosteroids significantly
      improved the survival rate and intellectual outcome of children with TBM.
      Enhanced resolution of the basal exudate and tuberculomas by steroids was shown
      by serial CT scanning. Corticosteroids did not affect ICP or the incidence of
      basal ganglia infarction significantly.

PMID- 9024452
TI  - Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome.
AB  - OBJECTIVE: Postmortem studies of fetuses, infants, and young children with fetal
      alcohol syndrome (FAS) have demonstrated a variety of severe central nervous
      system (CNS) anomalies. We undertook this magnetic resonance study (1) to assess
      the spectrum of CNS anomalies that occur in a clinical sample of typical patients
      with FAS who are medically stable; and (2) to examine the relationship between
      CNS and facial anomalies. METHODOLOGY: Magnetic resonance imaging was performed
      on a series of 10 patients (4 children, 3 adolescents, and 3 adults) who met
      criteria for FAS. We systematically evaluated each scan for brain anomalies and
      compared total brain tissue volume with that of healthy child, adolescent, and
      adult control subjects. RESULTS: Six patients had some type of midline anomaly,
      ranging from partial to complete callosal agenesis (three patients) to
      hypoplastic corpus callosum (one patient), cavum septi pellucidi (three
      patients), and cavum vergae (two patients). These midline anomalies were
      associated with a greater number of facial anomalies. Other brain anomalies
      identified included micrencephaly, ventriculomegaly, and hypoplasia of the
      inferior olivary eminences. CONCLUSION: Patients with classic FAS have a high
      incidence of midline brain anomalies. This finding is consistent with the concept
      that the midline CNS is a developmental field that is particularly susceptible to
      the teratogenic effects of alcohol. Furthermore, patients with more severe facial
      dysmorphologic characteristics are more likely to have midline brain anomalies.
      In addition, we observed a high incidence of micrencephaly with a wide range of
      severity.

PMID- 9024453
TI  - Pediatric work force: data from the American Board of Pediatrics.

PMID- 9024454
TI  - Quality of care: an overdue agenda.

PMID- 9024455
TI  - Data from randomized trial networks: when less is more.

PMID- 9024456
TI  - Improving our public health system's care for children with asthma.

PMID- 9024457
TI  - Vitamin B12 deficiency: a cause of abnormal movements in infants.

PMID- 9024458
TI  - Perineal and lip ulcerations as the presenting manifestation of hemangioma of
      infancy.

PMID- 9024459
TI  - The occurrence of Kostmann syndrome in preterm neonates.

PMID- 9024460
TI  - Treatment of severe La Crosse encephalitis with intravenous ribavirin following
      diagnosis by brain biopsy.

PMID- 9024462
TI  - Religious objections to medical care. American Academy of Pediatrics Committee on
      Bioethics.
AB  - Parents sometimes deny their children the benefits of medical care because of
      religious beliefs. In some jurisdictions, exemptions to child abuse and neglect
      laws restrict government action to protect children or seek legal redress when
      the alleged abuse or neglect has occurred in the name of religion. The American
      Academy of Pediatrics (AAP) believes that all children deserve effective medical
      treatment that is likely to prevent substantial harm or suffering or death. In
      addition, the AAP advocates that all legal interventions apply equally whenever
      children are endangered or harmed, without exemptions based on parental religious
      beliefs. To these ends, the AAP calls for the repeal of religious exemption laws
      and supports additional efforts to educate the public about the medical needs of
      children.

PMID- 9024461
TI  - "Inactive" ingredients in pharmaceutical products: update (subject review).
      American Academy of Pediatrics Committee on Drugs.
AB  - Because of an increasing number of reports of adverse reactions associated with
      pharmaceutical excipients, in 1985 the Committee on Drugs issued a position
      statement recommending that the Food and Drug Administration mandate labeling of
      over-the-counter and prescription formulations to include a qualitative list of
      inactive ingredients. However, labeling of inactive ingredients remains
      voluntary. Adverse reactions continue to be reported, although some are no longer
      considered clinically significant, and other new reactions have emerged. The
      original statement, therefore, has been updated and its information expanded.

PMID- 9024463
TI  - Acellular pertussis vaccine: recommendations for use as the initial series in
      infants and children. American Academy of Pediatrics Committee on Infectious
      Diseases.
AB  - In 1991 and 1992, the US Food and Drug Administration approved two acellular
      pertussis vaccines combined with diphtheria and tetanus toxoids for use as the
      fourth and fifth doses after the initial three-dose primary series with the
      standard whole-cell pertussis vaccine administered at 2, 4, and 6 months of age.
      Recently completed trials of acellular pertussis vaccines conducted in Europe
      have documented the efficacy of these vaccines when administered as a primary
      series in infancy. Based on these studies, two acellular pertussis vaccines,
      Tripedia (Connaught Laboratories, Swiftwater, PA) and ACEL-IMUNE (Wyeth-Lederle
      Laboratories, Pearl River, NY), were licensed by the Food and Drug Administration
      for the initial three-dose series. Additional acellular pertussis vaccines are
      likely to be licensed for use in infants in the future. The recommendations in
      this statement supplement previous American Academy of Pediatrics guidelines for
      the use of acellular pertussis vaccines.

PMID- 9024464
TI  - Therapy for children with invasive pneumococcal infections. American Academy of
      Pediatrics Committee on Infectious Diseases.
AB  - This statement provides guidelines for therapy of children with serious
      infections possibly caused by Streptococcus pneumoniae. Resistance of invasive
      pneumococcal strains to penicillin, cefotaxime, and ceftriaxone has increased
      over the past few years. Reports of failures of cefotaxime or ceftriaxone in the
      treatment of children with meningitis caused by resistant S pneumoniae
      necessitates a revision of Academy recommendations. For nonmeningeal infections,
      modifications of the initial therapy need to be considered only for patients who
      are critically ill and those who have a severe underlying or potentially
      immunocompromising condition or patients from whom a highly resistant strain is
      isolated. Because vancomycin is the only antibiotic to which all S pneumoniae
      strains are susceptible, its use should be restricted to minimize the emergence
      of vancomycin-resistant organisms. Patients with probable aseptic (viral)
      meningitis should not be treated with vancomycin. These recommendations are
      subject to change as new information becomes available.

PMID- 9024465
TI  - Poliomyelitis prevention: recommendations for use of inactivated poliovirus
      vaccine and live oral poliovirus vaccine. American Academy of Pediatrics
      Committee on Infectious Diseases.
AB  - A change in the recommendations for routine immunization of children is indicated
      because of the reduced risk of exposure to wild-type polio viruses and the
      continued occurrence of vaccine-associated paralytic poliomyelitis after oral
      polio vaccine (OPV). All children should receive four doses of vaccine before the
      child enters school. Regimens of sequential inactivated polio vaccine (IPV) and
      OPV, IPV only, or OPV only are acceptable. Each regimen has advantages and
      disadvantages. In special circumstances, one of the regimens is preferred or
      recommended. Because logistical problems with the current childhood immunization
      schedule may make these new recommendations difficult to implement immediately,
      their adoption likely will be gradual. Nevertheless, assuming continued progress
      toward global eradication and the development of new combination products, the
      routine use of an IPV-only regimen is likely to become desirable and feasible in
      future years.

PMID- 9024466
TI  - No sense making sense of State v Messenger.

PMID- 9024467
TI  - Lumbar puncture and the first simple febrile seizure.

PMID- 9024468
TI  - Gay and lesbian parents.

PMID- 9024469
TI  - Gay and lesbian parents.

PMID- 9024471
TI  - Why use the word "formula"?

PMID- 9024470
TI  - Facilitated communication.

PMID- 9024472
TI  - Teaching newborn care.

PMID- 9024473
TI  - Helping mothers cope with a critically ill child: a pilot test of the COPE
      intervention.
AB  - The purpose of this study was to pilot test the effects of a theoretically driven
      intervention program (COPE = Creating Opportunities for Parent Empowerment) on
      the coping outcomes of critically ill children and their mothers. Thirty mothers
      of 1- to 6-year-old children in a pediatric intensive care unit (PICU) were
      randomly assigned to receive COPE or a comparison program. Mothers who received
      the COPE program: (a) provided more support to their children during intrusive
      procedures; (b) provided more emotional support to their children; (c) reported
      less negative mood state and less parental stress related to their children's
      emotions and behaviors; and (d) reported fewer post-traumatic stress symptoms and
      less parental role change four weeks following hospitalization. Results indicate
      the need to educate parents regarding their children's responses as they recover
      from critical illness and how they can assist their children in coping with the
      stressful experience.

PMID- 9024474
TI  - Effect of support groups with coaching on adaptation to early stage breast
      cancer.
AB  - The effects of 8-week cancer support groups (CSGs) with and without coaching on
      adaptation were tested in a sample of 181 women with newly diagnosed early stage
      breast cancer. CSG participation with coaching resulted in higher quality of
      relationship with significant other at CSG conclusion; this effect was not
      sustained 8 weeks later. CSG participation had no effect on symptom distress,
      emotional distress, or functional status. On average, symptom distress was low,
      emotional distress was moderate, and functional status was relatively high.
      Independent of CSGs, symptom distress decreased and functional status increased
      over time from entry into the study to 16 weeks later. Further research is needed
      to determine the optimal starting time and length for CSGs.

PMID- 9024475
TI  - Effects of formal supports on stress outcomes in family caregivers of Alzheimer's
      patients.
AB  - The aim of this study was to examine whether formal support and coping would
      mediate the effects of primary stressors and caregiver characteristics on three
      stress outcomes: yielding of role, anxiety, and physical health. Secondary
      analysis of longitudinal data from a convenience sample of 452 spouse and adult
      child caregivers of Alzheimer's patients was used for model testing. Path
      analysis suggested that decreased physical health of the caregiver was best
      explained by caregiver overload. Caregiver anxiety was explained by lower levels
      of care receiver dependency, higher levels of caregiver overload, and higher
      levels of caregiver anxiety measured 1 year earlier. Yielding of the caregiver
      role was explained by the direct effect of higher levels of care receiver problem
      behaviors as well as more use of formal supports. Spouse relationship had a
      negative effect and care receiver dependency had a positive effect on yielding of
      the role through the mediating influence of formal support. Neither coping nor
      formal support mediated primary stressors and caregiver characteristics in the
      directions hypothesized.

PMID- 9024476
TI  - Infant age, context, and family system influences on the interactive behavior of
      mothers of infants with mental delay.
AB  - Interactive behavior of 30 mothers of infants with mental delay and 30 comparison
      mothers and infants was examined in relation to child age (first and second
      year), context (feeding versus teaching), maternal characteristics (family
      stress, coping resources), and family social system (maternal education). Groups
      were compared from two perspectives: with infants matched on mental age (9 and 19
      months MA), and on chronological age (8 and 18 months CA). Study mothers scored
      lower than comparison mothers during teaching but not during feeding in year 1
      with both MA and CA match, but only with the CA match in year 2. Study infants
      scored lower than comparison infants in both contexts in year 1, but not in year
      2. Groups did not differ on maternal or family measures. In year 1, group status,
      coping, and maternal education were predictive of mother interaction. In year 2,
      only maternal education was predictive. Results confirm the importance of type of
      match, context, and family system variables in understanding effects of child
      mental delay on maternal interactive behavior.

PMID- 9024477
TI  - Breastfeeding intention and outcome: a test of the theory of planned behavior.
AB  - Causal modeling was used to test the hypotheses of the theory of planned behavior
      for the prediction of prenatal breastfeeding intentions and postpartum
      breastfeeding outcomes with 135 childbearing women. In support of the theory,
      prenatal breastfeeding attitudes and perceived behavioral control predicted
      breastfeeding intentions (R2 = 23); however, the subjective norm variable failed
      to meet statistical criteria for model entry. Breastfeeding intentions weakly
      predicted duration of breastfeeding up to 6 weeks postpartum (R2 = .04). No
      additional empirically suggested prenatal and postpartum variables increased the
      explanatory power of the model in predicting breastfeeding intentions and
      duration. Implications for practice and research are discussed.

PMID- 9024478
TI  - Prenatal factors and birth outcomes in the public health service: a rural/urban
      comparison.
AB  - To determine whether predictors of birth outcomes differ for women in rural
      versus urban areas, data were obtained from the health records of women who
      received prenatal care through the Public Health Departments of a rural (N = 364)
      and urban (N = 415) setting. The rural group was more apt to be single, less
      educated, African-American, and have a lower income than the urban group. Rural
      women also had a higher incidence of low birth weight infants, which may be
      related to poor nutrition and low weight gain during pregnancy. Urban women had
      more maternal and neonatal complications, which may be related to a higher
      incidence of drug use and smoking. Membership in a rural or urban population did
      not predict low birth weight. Race, weeks gestation at first prenatal visit,
      number of total visits, and adequacy of diet and weight gain were significant
      predictors of birth weight. Neonatal complications were higher in the urban group
      and best predicted by poor diet, alcohol intake, and race. Both rural and urban
      women received inadequate prenatal care, as indicated by late entry into care and
      total number of visits. Alternative models of care which explore strategies to
      individualize care, while providing comprehensive care, should be investigated.

PMID- 9024479
TI  - Nurses' and resident physicians' perceptions of the process of collaboration in
      an MICU.
AB  - Ten intensive care unit nurses and 10 medical resident physicians were
      interviewed to compare their perceptions of the process of nurse-physician
      collaboration. The grounded theory method for concept development recommended by
      Strauss and Corbin (1990) was used. The core of the process of collaboration for
      both groups was working together. Two major antecedent conditions were found:
      being available, which included being in the right place, having time, and having
      appropriate knowledge; and being receptive, which included being interested in
      collaboration and having respect and trust for the other profession. The major
      outcomes of working together were described as improving patient care, feeling
      better in the job, and controlling costs. The findings of the study pull together
      disparate concepts associated with collaborative practice and provide direction
      for future research.

PMID- 9024480
TI  - Using key informant methods in organizational survey research: assessing for
      informant bias.
AB  - Specification of variables that reflect organizational processes can add an
      important dimension to the investigation of outcomes. However, many contextual
      variables are conceptualized at a macro unit of analysis and may not be amenable
      to direct measurement. In these situations, proxy measurement is obtained by
      treating organizational members as key informants who report about properties of
      the work group or organization. Potential sources of bias when using key
      informant methods in organizational survey research are discussed. Statistical
      procedures for assessment of rater-trait interaction as a type of informant bias
      are illustrated using data from a study in which multiple key informants were
      sampled to obtain proxy measurement of the organizational climate for caring
      among baccalaureate schools of nursing.

PMID- 9024481
TI  - Human immunodeficiency virus-indeterminate western blot and abortive infection.

PMID- 9024482
TI  - TRANSFUSION looks back, steps forward.

PMID- 9024483
TI  - Studies on platelets exposed to or stored at temperatures below 20 degrees C or
      above 24 degrees C.
AB  - BACKGROUND: Platelet concentrates (PCs) may be subjected to temperatures outside
      20 to 22 degrees C during shipping or storage, which may have an adverse effect
      on platelet quality. STUDY DESIGN AND METHODS: These studies systematically
      evaluated the effect of short-term exposure (< or = 24 hours) of platelets to
      temperatures above 22 degrees or below 20 degrees C as part of standard 5-day PC
      storage at 22 degrees C, as well as the effect of long-term storage (5 days) at
      24 and 26 degrees C. For the short-term exposure studies, up to 6 units of Day 1
      standard PCs were mixed, split, and returned to the containers. Test units were
      then stored without agitation in an incubator at a specific temperature (4, 12,
      16, or 18 degrees C) for various times up to 24 hours, after which they were
      stored with agitation at 22 degrees C. One unit acted as control and was stored
      at 20 to 22 degrees C throughout the 5-day storage period. Loss of platelet
      discoid shape was determined photometrically by the extent of shape change assay,
      by an increase in apparent platelet size by morphologic evaluation, and by
      swirling. RESULTS: A gradual loss of platelet discoid shape occurred at
      temperatures below 20 degrees C. For similar periods, a greater difference
      between test and control PCs was observed in units held at 4 degrees C than in
      those held at 16 degrees C. The data were fitted to an equation to relate
      platelet discoid shape (% of control) to exposure temperature and time. Assuming
      that a 20-percent decrease or more in the extent of shape change assay represents
      a significant loss in platelet viability, the equation predicts that such a loss
      occurs when the platelets are exposed to 16 degrees C for > or = 16 hours, to 12
      degrees C for > or = 10 hours, or to 4 degrees C for > or = 6 hours, whereas
      exposure to 18 degrees C for < or = 24 hours has no significant effect. Storage
      for 5 days at temperatures < or = 26 degrees C was not associated with any
      significant reduction in platelet discoid shape or other measures of platelet
      quality. CONCLUSION: There was a gradual loss of platelet discoid shape at
      exposure temperatures < 20 degrees C, which worsened as temperatures decreased
      and exposure times increased to 24 hours. This relationship can be described in
      an equation that could be used as a guideline for allowable exposure conditions.

PMID- 9024484
TI  - The expression of p-selectin during collection, processing, and storage of
      platelet concentrates: relationship to loss of in vivo viability.
AB  - BACKGROUND: Recent studies suggested that platelet activation with surface
      expression of p-selectin on stored platelets may be related to a loss of
      viability. At present, there has been no thorough investigation of the extent or
      significance of p-selectin expression during the collection, processing, and
      storage of platelet concentrates (PCs) under various conditions. STUDY DESIGN AND
      METHODS: Platelet surface expression of p-selectin (CD62) was determined on fixed
      platelet samples using fluorescein-conjugated monoclonal antibodies. Platelet
      viability was assessed by autologous transfusion of platelets stored for 5 days
      and labeled with either 51Cr or 111in. RESULTS: Little (2-10%) platelet
      expression of p-selectin was found in whole blood and platelet-rich-plasma
      preparations, whereas PCs showed a substantial increase in p-selectin expression
      to levels of 20 to 30 percent. Both fresh PCs and those stored for 5 days,
      obtained with one cell separator (MCS, Haemonetics) showed substantially lower
      levels of p-selectin expression than PCs from two other cell separators (Spectra,
      COBE, and CS-3000 with TNX-6, Baxter Healthcare). Exposure of platelets to EDTA,
      cold, or a pH below 6.2, conditions that are known to result in the loss of
      viability upon transfusion, produced substantial and irreversible p-selectin
      expression. PCs with a pH of 6.2 to 6.8 (conditions in which no loss of viability
      has been demonstrated) also showed pronounced p-selectin expression, which
      returned to control values after incubation at 37 degrees C in plasma at pH 7.0
      to 7.2. With storage under current conditions the in vivo studies (n = 61)
      demonstrated a rather poor correlation between p-selectin expression and the
      percentage of recovery (r = -0.25) but a somewhat better correlation with
      survival (r = -0.42). Better correlations were observed with the extent of shape
      change, lactate, and hypotonic shock response. CONCLUSION: These studies show
      that p-selectin expression on the platelet surface is a predictor of platelet
      viability, although the extent of shape change and the hypotonic shock response
      may be more sensitive.

PMID- 9024485
TI  - Inhibition of cytokine accumulation and bacterial growth during storage of
      platelet concentrates at 4 degrees C with retention of in vitro functional
      activity.
AB  - BACKGROUND: The potential for bacterial contamination limits the storage of
      platelet concentrates (PCs) at 22 degrees C to 5 days. In addition, storage of
      platelets under conventional protocols for longer times (> 3 days), in the
      absence of white cell filtration, has been correlated with incidents of cytokine
      associated febrile reaction in recipients. It has been demonstrated that the
      addition of a reagent mixture of second-messenger effectors allows platelets
      stored at 4 degrees C to maintain significant in vitro functional activity. Thus,
      the effects of 4 degrees C storage on the growth of bacteria and the accumulation
      of cytokines by the white cell fraction of PCs were analyzed to demonstrate the
      benefits of this refrigerated storage system. STUDY DESIGN AND METHODS: The
      platelet storage solution was added directly to PCs obtained from the blood bank,
      and these treated PCs were stored at 4 degrees C without agitation. In parallel,
      control PCs were stored according to standard blood-banking procedures. On Days
      1, 3, 5, and 9, the PCs were measured for the plasma concentrations of cytokines.
      Treated and control PCs stored at 4 degrees C and 22 degrees C were inoculated
      with low-titer Staphylococcus aureus, and bacterial growth was measured over a 5
      day period. RESULTS: Control PCs displayed a time-dependent increase in the
      plasma concentration of interleukin 6, interleukin 1 beta, and tumor necrosis
      factor alpha. These conventionally stored PCs also displayed a time-dependent
      increase in the bacteria titer. In contrast, the treated PCs stored at 4 degrees
      C displayed no accumulation of the above cytokines in the plasma fraction and no
      increase in bacteria titer above the initial inoculation. CONCLUSION: The storage
      of PCs at refrigerated temperatures inhibits the accumulation of white cell
      produced cytokines in the PCs, an effect that could alleviate cytokine-associated
      febrile transfusion reactions The 4 degrees C storage was also bacteriostatic,
      which indicates that the storage of PCs at that temperature increases safety by
      decreasing the potential for sepsis. Thus, the ability to store PCs at 4 degrees
      C may allow extension of the storage limit beyond 5 days.

PMID- 9024486
TI  - Rejuvenation of irradiated AS-1 red cells.
AB  - BACKGROUND: Gamma irradiation of blood components is used to prevent transfusion
      associated graft-versus-host disease. The demand for irradiated blood components
      is increasing because of the increase in directed donation by family members.
      Irradiated units currently have a recommended maximum storage life of 28 days.
      Since in vivo recovery is related to red cell ATP levels, rejuvenation of stored
      irradiated units using a pyruvate-inosine phosphate-adenine additive was
      explored. STUDY DESIGN AND METHODS: Units of AS-1 red cells from 16 volunteer
      donors were divided into two equal volumes and one split unit from each was
      irradiated with 25 Gy. Ten units were irradiated on Day 5, 6, or 7 of 4 degrees C
      storage and 6 units were irradiated on Day 1 of 4 degrees C storage. All units
      were rejuvenated for 1 hour at 37 degrees C using a pyruvate-inosine-phosphate
      adenine additive on Day 42 of 4 degrees C storage. Units were assayed for ATP, 2,
      3 DPG and supernatant sodium, potassium, and glucose. RESULTS: ATP and 2, 3 DPG
      levels were restored equally well in irradiated and non-irradiated units. The
      previously reported irradiation-induced red cell potassium-sodium shift was
      demonstrated. Supernatant potassium and sodium levels did not reverse 1 hour
      after rejuvenation was completed. There was no significant difference in results
      between units irradiated on Day 1 or Day 5, 6, or 7. CONCLUSION: Red cell ATP and
      2, 3 DPG levels were restored in irradiated AS-1 units stored at 4 degrees C for
      42 days using a pyruvate-inosine-phosphate-adenine rejuvenation additive.

PMID- 9024487
TI  - Automatic volumetric capillary cytometry for counting white cells in white cell
      reduced plateletpheresis components.
AB  - BACKGROUND: As the benefits of white cell (WBC)-reduced blood components become
      increasingly apparent, the need has arisen for a simple, automated WBC-counting
      technique that is sensitive to low WBC concentrations. Automated volumetric
      capillary cytometry was evaluated for its ability to quantify residual WBCs in
      WBC-reduced plateletpheresis components. STUDY DESIGN AND METHODS: The volumetric
      capillary cytometry system evaluated uses a laser to excite fluorescent dye
      labeled nucleated cells. The number of nucleated cells per microliter is
      reported. Four studies were performed: linearity, precision of results near the
      value of 5 x 10(6) WBCs per unit, the limit of detection, and correlation to the
      Nageotte manual counting method. RESULTS: Assay values correlated to expected
      values (range, 0-125 WBC/microliter) with an r2 > 0.99. In the range of 5 x 10(5)
      WBCs per unit the CV was 8.5 percent, and concentration differences of 0.15 log10
      were detectable. The limit of detection was 1.0 WBCs per microliter (95% upper
      confidence limit). The assay correlated to the Nageotte method with an r2 of
      0.98, slope of 1.0, and y-intercept of 2.0 WBCs per microliter. Assay results
      were 10 to 15 percent higher than Nageotte results, in samples with values near 5
      x 10(6) WBCs per unit. Technician time per sample was 2 to 3 minutes. CONCLUSION:
      Volumetric capillary cytometry is precise and sensitive to small differences in
      WBC concentration in the range of clinical interest. The device provides an
      efficient new method for quality assurance and control of WBC-reduced
      plateletpheresis products.

PMID- 9024488
TI  - Molecular background of VS and weak C expression in blacks.
AB  - BACKGROUND: The Rh system is complex and consists of as many as 45 different
      antigens. Red cells of about 25 percent of the black population carry VS an Rh
      system antigen (Rh20), but this antigen is very rare in whites. VS positivity is
      always associated with a weak expression of e, and usually also of C. STUDY
      DESIGN AND METHODS: The RH genes of 11 black VS-positive donors were studied.
      Transcripts were sequenced for four VS-positive donors, three of whom had red
      cells with a weak expression of C. In the other donors, only analysis of genomic
      DNA was carried out. RESULTS: The occurrence of VS was shown to be related to a
      single-point mutation in exon 5 of the RHCE gene (cytosine 733 guanine, leading
      to the Leu245Val substitution). The presence of this polymorphism in exon 5 may
      explain the simultaneously occurring weak e, because the E/e polymorphism is
      located in the same exon. Study of VS-positive donors with different Rh
      phenotypes showed that the polymorphism can occur in different alleles of the
      RHCE gene. In all three donors whose red cells showed a weak expression of C, a
      hybrid D-CE-D transcript was found, containing exon 4, 5, 6, 7, and (probably) 8
      from the RHCE gene. No transcripts were encountered carrying DNA markers normally
      associated with C expression. CONCLUSION: It is therefore postulated that the
      hybrid gene is responsible for the weak expression of C in these individuals. The
      hybrid gene carried a Leu62Phe substitution, as well as the Leu245Val
      substitution responsible for VS. The gene most probably cosegregates with a C
      allele encoding Cys 16 (normally encoded only by the C allele) and Val245
      (responsible for VS antigenicity when encoded by the RHCE gene). This explains
      the combination of weak expression of C and VS positivity that is frequently
      found in blacks.

PMID- 9024489
TI  - Cost-effectiveness of expanded human immunodeficiency virus-testing protocols for
      donated blood.
AB  - BACKGROUND: This study was designed to estimate the cost-effectiveness of
      expanding the human immunodeficiency virus (HIV)-testing protocol for donated
      blood beyond screening for HIV antibodies to further reduce the risk of HIV
      transmission through transfusion. STUDY DESIGN AND METHODS: A Markov decision
      analysis model was developed to estimate the cost-effectiveness of HIV antibody
      testing (at a cost of $5/unit) and of adding to that protocol a second HIV test,
      either plasma p24 antigen detection or RNA polymerase chain reaction (PCR) (at
      costs of $5/unit and $8/unit, respectively). Test efficacy was projected from
      anticipated window-period reductions (6 days for p24 antigen, 11 days for RNA
      PCR), and donor seroconversion rates were derived from the Retrovirus
      Epidemiology Donor Study. RESULTS: On the basis of current estimates of HIV
      prevalence rates in blood donors (1/10,000) and 16 million annual transfusions in
      the United States HIV antibody testing prevents 1568 cases of transfusion
      acquired HIV infection each year at a cost of $3600 per quality-adjusted year of
      life saved. The addition of p24 antigen testing would prevent 8 more cases at a
      net additional cost of $60 million annually ($2.3 million/quality-adjusted life
      year); RNA PCR testing would prevent 16 more cases at a net additional cost of
      $96 million annually ($2.0 million/ quality-adjusted life year). CONCLUSION:
      Although expanding the donor HIV screening protocol with p24 antigen or RNA PCR
      testing will prevent rare cases of transfusion-associated HIV, the cost
      effectiveness of such an addition is predicted to be far below that of most
      medical interventions. Thus, HIV test protocol additions are unlikely to provide
      cost-effective improvements to blood safety in the United States.

PMID- 9024490
TI  - Comparative performances of enzyme-linked immunosorbent, western blot, and
      polymerase chain reaction assays for human T-lymphotropic virus type II infection
      that is endemic among Indians of the Gran Chaco region of South America.
AB  - BACKGROUND: Human T-cell lymphoma/leukemia viruses types I and II (HTLV-I and
      HTLV-II) are related exogenous human retroviruses. The former is definitely
      pathogenic while disease association with the latter is unclear. There are two
      subtypes of HTLV-II, A and B. Currently, enzyme-linked immunosorbent assays
      (ELISAs) based on HTLV-I antigens are used to screen for the presence of HTLV-I
      and -II antibodies. Confirmation and subtyping are accomplished by Western blot
      (WB) or ELISAs based on HTLV-I whole viral antigens and/or HTLV-I and HTLV-IIA
      peptides. The sensitivity and specificity of these serologic assays were compared
      to those of HTLV-I and-II-specific polymerase chain reaction (PCR) assays in
      tests on samples from Indians from South America in whom the HTLV-IIB subtype is
      endemic. STUDY DESIGN AND METHODS: Sera from 246 Gran Chaco Indians were
      evaluated for HTLV antibodies with the use of four ELISAs (Retrotek HTLV-I;
      Cambridge Biotech rgp21 enhanced HTLV-I/II; Vironostika HTLV-I/II; and Select
      HTLV-I/II), and a WB assay. Peripheral blood leukocyte DNA from each Indian was
      analyzed for HTLV-I or HTLV-II pol DNA via PCR. Fifteen of the PCR-positive
      samples were further subtyped via cloning and sequencing and/or oligomer
      restriction. RESULTS: Ninety-seven samples (39%) were positive for HTLV-II by
      serologic and/or PCR assays. All 15 positive DNA samples that were further
      analyzed were of the HTLV-IIB subtype and were clustered as a highly conserved
      phylogenetic group. Comparative analyses indicate that the sensitivity and
      specificity of the various assays were: PCR, 97 and 100 percent; Retrotek, 70 and
      91 percent; Cambridge Biotech, 74 and 96 percent; Vironostika, 73 and 99 percent;
      Select 72 and 98 percent; and WB, 70 and 100 percent. CONCLUSION: The
      sensitivities of the tested HTLV serologic assays were comparable. However, the
      specificity of the Retrotek ELISA was significantly lower than that of the
      others. When positive, the subtyping assays were very specific. However, PCR
      assays would seem preferable or to be a necessary adjunct for the sensitive
      detection of HTLV-IIB infection.

PMID- 9024491
TI  - Transfusion transmission of human T-lymphotropic virus type I (HTLV-I) from an
      asymptomatic blood donor: conservation of LTR U3, env, and tax nucleotide
      sequences in a recipient with HTLV-I-associated myelopathy.
AB  - BACKGROUND: Transfusion of human T-lymphotropic virus type I (HTLV-I)
      contaminated blood is sometimes linked with the rapid onset of HTLV-I-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) in immunocompromised
      recipients. STUDY DESIGN AND METHODS: This study addressed the question of
      whether HTLV-I variants could emerge in an immunocompromised patient who
      developed HAM/ TSP after the transfusion of blood from an asymptomatic HTLV-I
      carrier. Base pairs (n = 2327) of the HTLV-I genome located in the LTR U3 region
      and parts of the env and tax genes were sequenced and compared to the isolated
      identified in the asymptomatic blood donor and to well-known ATK-1 and H5
      strains. The same analysis was performed on another set of samples from an
      asymptomatic HTLV-I-positive blood donor and a similar blood recipient. RESULTS:
      No critical changes in nucleotide sequences were identified in the
      immunosuppressed HAM/TSP patient when compared with the nucleotide sequences of
      the corresponding blood donor, the other asymptomatic blood donor and recipient
      or the ATK-1 and H5 strains. CONCLUSION: Immunosuppression does not seem to favor
      the emergence of particular nucleotide sequences in the genome located in the LTR
      U3 region or in parts of the env and tax genes in transfused patients who develop
      HAM/TSP.

PMID- 9024492
TI  - Indeterminate human immunodeficiency virus type 1 western blot may indicate an
      abortive infection in some low-risk blood donors.
AB  - BACKGROUND: The infectious status of persons with an indeterminate human
      immunodeficiency virus type 1 (HIV-1) Western blot must be established. STUDY
      DESIGN AND METHODS: Evaluation of the CD4 and CD8 T-cell subsets and the
      expression of HIV-1-integrated sequences by Southern blot and polymerase chain
      reaction were studied in a group of low-risk subjects with an indeterminate
      Western blot. RESULTS: From a total of 45,000 blood donors and 50 patients with
      chronic renal failure on hemodialysis who were tested during the period of 1985
      through 1990, 50 sera (0.1%) had an indeterminate Western blot. A low CD4:CD8
      ratio (0.7-1.2) was detected in 14 of 24 tested subjects, whereas the
      unfractionated and adherence-enriched cells of 7 (32%) and 5 (23%) of 22
      patients, respectively, could be stained with a p24 monoclonal antibody. A
      transient positive culture was detected in 3 of 20 subjects, but these viral
      isolates could not be transmitted to CEM-A310 cells. Ultracentrifuged culture
      supernatants hybridized under high-stringency conditions with genomic gag-pol (4
      cases), env (3 cases), and tat (1 case) cDNA fragments of the HXB2 HIV-1 clone.
      In one case, DNA obtained from adherent but not unfractionated mononuclear cells
      contained 3.3- and 3.9-kb env- and gag-pol-related HIV-1 sequences, respectively;
      these sequences were heavier than expected. Polymerase chain reaction analysis
      for gag and pol but not env sequences was positive in 1 and 2 of 7 cases,
      respectively. A female patient with a positive viral culture and who was positive
      for pol in polymerase chain reaction demonstrated a full seroconversion 19 months
      later. CONCLUSION: The results strongly suggest that, rarely, some low-risk
      subjects with indeterminate Western blot results might be infected with low-level
      replicative strains or HIV-related viruses; thus, an exhaustive immunologic and
      virologic workup is needed for the investigation of these subjects.

PMID- 9024493
TI  - Prevalence of hepatitis C virus and genotype distribution in an Australian
      volunteer blood donor population.
AB  - BACKGROUND: This study was undertaken to assess the prevalence of hepatitis C
      virus (HCV) antibody and RNA in first-time blood donors and to examine the HCV
      genotype distribution. STUDY DESIGN AND METHODS: A third-generation enzyme-linked
      immunosorbent assay (ELISA) was used to screen 34,725 donors for HCV antibodies.
      Donors who were repeatably reactive were tested in two immunoblot assays-a second
      generation and a third-generation recombinant immunoblot assay-as well as by a
      polymerase chain reaction (PCR) assay. PCR-positive donors were genotyped. All
      samples were screened for alanine aminotransferase levels. RESULTS: The ELISA
      repeat reactivity rate was 0.55 percent. PCR testing showed that 69 (38%) of the
      183 ELISA-reactive samples contained HCV RNA. The third-generation recombinant
      immunoblot assay identified all 69 viremic samples as antibody positive; however,
      only 63 tested positive on the second-generation immunoblot. The remaining six
      PCR-positive donors tested antibody-indeterminate to the core peptide. All six of
      these donors had HCV subtype 3a infections. Genotype distribution among 58
      samples showed that 34 were type 1, of which 22 could be further subtyped as 1a
      (16) and 1b (6); 2 were 2a; 5 were 2b; and 17 were subtyped as 3a. Donors
      infected with 2b and 3a had reduced antibody reactivity to the NS4 and NS3
      peptides only on the second-generation immunoblot. CONCLUSION: The prevalence of
      confirmed anti-HCV and viral RNA in new donors is 0.29 and 0.2 percent,
      respectively. The third-generation recombinant immunoblot assay was more
      sensitive than the second-generation immunoblot assay in detecting 2b and 3a HCV
      subtypes. The inclusion of the NS5 peptide in the third-generation recombinant
      immunoblot did not result in positive tests in any additional donors. Rather, the
      improvement was due to the increased detection of NS3 and, to a lesser extent,
      NS4 antibodies. Subtypes 1a and 3a were most prevalent in this population.

PMID- 9024495
TI  - Soluble interleukin 2 receptor and soluble CD8 levels in previously treated human
      immunodeficiency virus-negative hemophiliacs multiply transfused with a
      monoclonal antibody-purified factor VIII concentrate.
AB  - BACKGROUND: Serum levels of the soluble interleukin 2 receptor (sIL-2R) and
      soluble CD8 (sCD8) may be used as markers of T-cell activation. The course of
      serum levels of sIL-2R and sCD8 in hemophiliacs who were treated first with an
      intermediate-purity factor VIII concentrate and then with a monoclonal antibody
      (MoAb)-purified factor VIII concentrate are reported. STUDY DESIGN AND METHODS:
      Serum samples taken before the administration of the MoAb-purified concentrate
      and after 2 and 5 years of its administration to 20 human immunodeficiency virus
      negative patients with hemophilia A were analyzed. Eighteen healthy age-matched
      men were used as controls. RESULTS: The sIL-2R and sCD8 levels were higher in
      patients treated with intermediate-purity concentrates than in controls (p =
      0.006 and p = 0.0005, respectively). The sIL-2R levels showed a decrease after 5
      years of treatment with the MoAb-purified concentrate (p = 0.018 for the
      difference between 2 and 5 years), to levels that were not significantly
      different from those in controls. Although sCD8 levels tended to decrease at 5
      years (p = 0.09, for the difference between 2 and 5 years), they remained higher
      than those in controls (p = 0.0005 and p = 0.0016 at 2 and 5 years,
      respectively). The ratio of sCD8 and sIL-2R tended to increase between 2 and 5
      years (p = 0.07). The sIL-2R and sCD8 levels were not related to the numbers of T
      lymphocytes and HLA-DR-positive T-lymphocytes in peripheral blood. Nor was a
      relation demonstrated between sIL-2R levels and CD4-positive cell numbers or
      between sCD8 levels and CD8-positive cell numbers. Although a relation with
      chronic hepatitis C cannot be excluded, it seems more likely that changes in sIL
      2R levels are due to the use of the MoAb-purified concentrate. CONCLUSION:
      Elevated levels of sIL-2R and sCD8 were found in multiply transfused human
      immunodeficiency virus-negative hemophiliacs. After treatment was changed to the
      use of a MoAb-purified concentrate. sIL-2R levels decreased. These findings
      suggest a change in immune stimulation that is remarkable, because signs of
      activation in the effector phase seem to have continued despite normalization in
      the proliferative phase.

PMID- 9024494
TI  - Preapheresis peripheral blood CD34+ mononuclear cell counts as predictors of
      progenitor cell yield.
AB  - BACKGROUND: Peripheral blood progenitor cells, harvested by apheresis after
      mobilization, provide rapid hematologic recovery after high-dose chemotherapy.
      However, because harvesting these cells is expensive and time-consuming, there
      has been much interest in optimizing collection protocols. An investigation was
      made to determine whether, in this clinical setting, peripheral blood progenitor
      cell yields may be predicted from preapheresis progenitor cell counts, allowing
      the length of each procedure to be "fine tuned" to achieve specific target goals.
      STUDY DESIGN AND METHODS: Preapheresis peripheral blood CD34+ cell and total
      colony-forming cell counts were assessed before 78 peripheral blood progenitor
      cell collections from 13 consecutive patients were performed. Preapheresis counts
      were correlated with actual progenitor cell yields. Factors affecting this
      correlation were analyzed. RESULTS: With the use of linear regression analysis
      preapheresis progenitor cell counts were found to correlate significantly but
      weakly with actual yields per kg of body weight per liter of blood processed
      (CD34+ cells: r = 0.43; colony-forming cells: r = 0.56). Further analysis
      revealed two possible causes: 1) circulating progenitor cell concentrations
      fluctuate widely during harvest, which implies that preapheresis counts are not
      representative of actual concentrations during apheresis, and 2) the efficiency
      with which apheresis machines extract mononuclear cells varies greatly between
      procedures. CONCLUSION: Preapheresis CD34+ and colony-forming cell counts
      correlated poorly with subsequent yields in this clinical setting, which suggests
      that it is not practical to use such counts to predict with certainty the length
      of apheresis needed to achieve a target yield.

PMID- 9024496
TI  - The American Association of Blood Banks founded 50 years ago.

PMID- 9024497
TI  - Current status of microbial contamination of blood components: summary of a
      conference.

PMID- 9024498
TI  - A modified flow cytometric method for counting very low numbers of white cells in
      platelet concentrates.

PMID- 9024499
TI  - Detection of acquired B antigen by monoclonal anti-B blood grouping reagents.

PMID- 9024500
TI  - Blood donor management in a high-risk environment: The National Blood Transfusion
      Service of the Ivory Coast.

PMID- 9024501
TI  - Effects of granulocyte-colony-stimulating factor and interleukin-2 on ascites
      formation and the survival time of nude mice bearing human ovarian cancer cells.
AB  - The aim of this study was to elucidate the effect of intraperitoneal (i.p.)
      instillations of granulocyte-colony-stimulating factor (G-CSF) and/or interleukin
      2 (IL-2) on ascites formation and the survival time of nude mice with malignant
      ascites, produced by i.p. inoculation of human ovarian cancer cells. When the
      nude mice were treated with medium alone, ascites was observed in all mice 28
      days after tumor inoculation. When the mice were treated with cis
      diamminedichloroplatinum(II) (cisplatin) alone, G-CSF alone or IL-2 alone, it
      took 35 days for the ascites to form in all mice. When cisplatin was combined
      with G-CSF or IL-2, one of ten mice did not form ascites during the observation
      period. Surprisingly, when G-CSF and IL-2 were simultaneously administered,
      ascites formation was not observed in any mice. Although i.p. treatment with
      cisplatin alone significantly prolonged the survival time, compared to medium
      alone, the lytic activity of spleen cells against HRA cells was significantly
      suppressed. When G-CSF or IL-2 was combined with cisplatin, the suppression by
      cisplatin was eliminated and subsequently resulted in a prolongation of the
      survival time. When G-CSF was combined with IL-2, both the peritoneal and splenic
      macrophages/ monocytes were stimulated and the splenic lytic activity was about
      double that following treatment with G-CSF alone on IL-2 alone, suggesting that
      complete inhibition of ascites formation results not only from a significant
      increase of the peritoneal macrophages but also from enhancement of the lytic
      activity. Two mice, died from dissemination of tumor in the abdominal cavity, but
      eight mice survived without tumor for more than 90 days. As confirmed by
      monitoring body weight and hematocrit, G-CSF and IL-2 seemed to have no adverse
      effect. From these results, we conclude that a combination therapy with G-CSF and
      IL-2 might be of clinical use for inhibiting large amounts of ascites, which may
      inhibit therapeutic effects for ovarian cancer patients.

PMID- 9024502
TI  - Antigen-presenting function of human peritoneum mesothelial cells isolated from a
      pancreatic carcinoma patient after mutant Ras peptide vaccination.
AB  - Mesothelial cells obtained from ascites fluid of a Ras-peptide vaccinated
      pancreatic adenocarcinoma patient were cultured in vitro. Fresh isolated cells
      expressed HLA class II molecules, which were lost upon culture, but could be up
      regulated after coculture with human recombinant interferon-gamma. The antigen
      presenting capacity of these mesothelial cells was tested with allogeneic
      peripheral blood mononuclear cells (PBMC) in a mixed lymphocyte mesothelial cell
      culture and by stimulating autologous PBMC with purified protein derivative of
      Mycobacterium tuberculosis. Cloned T cells from the same patient allowed us to
      test the ability of mesothelial cells to present a mutant Ras-derived peptide to
      specific T cells in a DLA-DR-restricted manner. Mesothelial cells effectively
      stimulated allogeneic resting T lymphocytes to proliferate and presented soluble
      protein antigen or a mutant Ras-derived peptide to specific T cells, indicating
      that they display processing and presenting capabilities. Since mesothelial cells
      are in close anatomical relationship with intraabdominal malignancies, they may
      contribute to stimulation of specific T cells by endocytosing tumour-specific
      antigens and presenting them to T lymphocytes. This could be a possible mechanism
      in which mesothelial cells participate in maintaining local specific immunity in
      patients already primed.

PMID- 9024503
TI  - Treatment of human lung carcinoma xenografts with a combination of 131I-labelled
      monoclonal antibody Po66 and doxorubicin.
AB  - Po66, a mouse monoclonal antibody, is directed against an intracytoplasmic
      antigen present in human lung squamous cell carcinoma cells. In previous work it
      was found that the co-administration of 125I-radiolabelled Po66 and doxorubicin
      strongly enhanced the uptake of radioactivity by the tumour. The present-work was
      designed to evaluate, in a tumour-bearing mouse model of lung carcinoma, the
      ability of 131I-labelled Po66 to retard tumour growth when injected alone, or in
      combination with doxorubicin (8 mg kg-1 at 1-week intervals). A single dose of
      550 microCi 131I-Po66 alone had no effect on tumour growth, whereas three
      fractionated doses of 250 microCi 131I-Po66 decreased it over two doubling times
      from 14.5 +/- 1.5 days for untreated control mice to 24.8 +/- 2.7 days. Mice
      treated with doxorubicin alone had a double tumour doubling time of 22.6 +/- 4.9
      days, compared to 35.2 +/- 2.9 days (1.55-fold increase) in mice treated with
      doxorubicin and a single dose of 550 microCi 131I-Po66. Doxorubicin combined with
      three fractionated doses of 250 microCi 131I-Po66 provoked a twofold decrease in
      tumour growth compared to mice treated with doxorubicin alone. The administration
      of fractionated doses of 131I-Po66 simultaneously with doxorubicin resulted in a
      highly delayed mortality, which was not observed when 131I-Po66 was administered
      after doxorubicin. Thus, in a non-small-cell lung tumour model, a 131I
      radiolabelled monoclonal antibody, directed against an intracellular antigen,
      significantly potentiated the effect of chemotherapy. Such a therapeutic approach
      could be used as an adjuvant therapy and improve the effect of chemotherapy on
      distant small metastases.

PMID- 9024504
TI  - Human T lymphocyte activation in the presence of acute myelogenous leukaemia
      blasts: studies of allostimulated interferon-gamma secretion.
AB  - Normal peripheral blood mononuclear cells (PBMC responders) were cultured
      together with non-irradiated allogeneic PBMC (more than 95% leukaemia blasts)
      derived from patients with acute leukaemia (referred to as leukaemic PBMC
      stimulators). Cytokine secretion was determined as cytokine concentrations in
      supernatants. Both normal PBMC and enriched CD4+ and CD8+ T cells responded to
      allostimulation with interferon (IFN gamma) secretion. Interleukin-I (IL-1)
      receptor antagonist and IL-2-neutralizing antibodies decreased IFN gamma
      secretion. Exogenous IL-1 beta, IL-2 and IL-7 increased allostimulated IFN gamma
      secretion, whereas decreased levels were seen in the presence of IL-6, IL-10 and
      granulocyte-colony-stimulating factor (G-CSF). During allorecognition IFN gamma
      neutralizing antibodies decreased acute myelogenous leukaemia (AML) blast
      secretion of G-CSF. We conclude that (i) both CD4+ and CD8+ T cells show
      allostimulated cytokine secretion in response to allogeneic stimulator cells
      containing a dominating population of native, cytokine-secreting leukaemia
      blasts, and (ii) IFN gamma released during this response can modulate the
      function of allogeneic AML blasts.

PMID- 9024505
TI  - Interleukin-2 and interleukin-7 augment the cytolytic activity and expand the
      antitumor killing spectrum of alpha CD3-induced activated killer cells: potential
      use in the immunotherapy of non-immunogenic tumors.
AB  - This study investigates the effect of different cytokines on the growth and
      antitumor activity of the alpha CD3-induced killer cells CD3-AK, and the
      potential of the use of CD3-AK cells in cancer immunotherapy. Eight cytokines
      were tested. Only three (interleukin-2, -4 and -7) were able to support the
      growth of CD3-AK cells, which selectively killed different tumor targets of
      diversified origin. Culturing in interleukin-4 (IL-4) or IL-7 alone could
      maintain the growth of CD3-AK cells for 6-8 days. Only IL-2 could maintain long
      term growth, but further addition of IL-4 exerted an inhibitory effect, which
      terminated the cell growth in 2 weeks. In contrast, despite the fact that IL-7
      inhibited the proliferation of CD3-AK cells cultured in IL-2, as determined by
      [3H]thymidine uptake, the recovery of viable cells was not reduced. In 10 days,
      CD3-AK cells cultured in IL-2 alone or IL-2 plus IL-7 increased 160- or 176-fold
      respectively. There is an inverse relationship between the in vitro growth
      ability and Fas expression on the CD3-AK cells. Further, IL-7 increased the
      cytolytic activity of the CD3-AK cells two- to threefold. CD3-AK cells could be
      maintained in IL-2 or IL-2 plus IL-7 for 60-240 days or more. The long-term
      cultured CD3-AK cells not only possessed a high level of cytolytic activity, but
      also showed a wide spectrum of killing with different tumor targets; the normally
      "resistant" targets, such as EL-4 lymphoma, fibrosarcoma, or melanoma, became
      susceptible. When the in vivo antitumor activity of the CD3-AK cells against a
      non-immunogenic tumor. EL-4, was tested by tumor-neutralization experiments, we
      found that only the long-term-cultured cells gave significant protection, with
      those maintained in both IL-2 and IL-7 giving the highest degree of protection.
      Thus, these long-term-cultured CD3-AK cells may have the potential to be used for
      immunotherapy of a variety of tumors whatever their immunogenicity.

PMID- 9024506
TI  - Prognostic markers for survival in patients with metastatic renal cell carcinoma
      treated with interleukin-2.
AB  - Interleukin-2 (IL-2)-based immunotherapy can induce antitumor responses in about
      25% of patients with metastatic renal cell carcinoma (RCC). The limited effect
      and the severe side-effects of IL-2 have led us to perform a prognostic factor
      analysis. Twenty-four patients with metastatic RCC were treated with IL-2. Flow
      cytometry and immunohistology were used to determine DNA ploidy, HLA-II
      expression on tumor cells, and the presence of macrophages in the primary tumor.
      These variables were examined in relation to survival. The 4-year overall
      survival rate was 38%. Forty-six percent of the primary tumors were aneuploid.
      All tumors, except one, showed HLA-II expression and macrophage presence. A
      statistically significant correlation (r = 0.66, P = 0.002) was found between HLA
      II expression and macrophage presence. Patients with high HLA-II expression had a
      lower 4-year survival (22% compared to 50%), as had patients with high macrophage
      presence (20% compared to 42%). Of note, patients characterized by both high HLA
      II and high macrophage expression had the worst survival (13% compared to 50%).
      We concluded that DNA ploidy was not predictive for survival, whereas HLA-II
      expression and macrophage presence may represent valuable prognostic factors
      related to survival. The present data suggest that more of the patients with no
      or moderate HLA-II expression and/or no or moderate macrophage presence in the
      primary tumor could survive with persistence of their malignant disease after
      having received IL-2 immunotherapy, as compared to patients with both high HLA-II
      and high macrophage expression.

PMID- 9024507
TI  - Levamisole regulates the proliferation of murine liver T cells through Kupffer
      cell-derived cytokines.
AB  - We have previously shown that levamisole increases the cytotoxic, cytostatic, and
      proliferative activity of murine nonparenchymal liver cells (NPC) in vitro. We
      have also shown that the nonadherent subpopulation of NPC, which are composed
      predominantly of T lymphocytes, is very responsive to this agent when
      administered to mice. Kupffer cells or immigrant macrophages are also responsive
      to levamisole but to a lesser extent. These findings prompted us to investigate
      changes in cytokine production by NPC following-treatment of mice with levamisole
      (25 mg/kg, i.p.), which may help explain the observed alterations in the immune
      functions of these cells. We found that levamisole treatment of mice causes a
      threefold increase in production of interferon (IFN) alpha/beta by adherent NPC
      (more than 80%-90% Kupffer cells) in vitro. When IFN alpha/beta was added to
      cultured cells, it decreased the proliferative capacity of liver T cells in a
      dose-dependent manner. In contrast, the addition of anti-IFN alpha/beta was shown
      to augment levamisole-induced proliferation of unfractionated NPC and Kupffer
      cells. NPC production of interleukin 1 (IL-1) and interleukin-6 (IL-6) in vitro
      was also increased threefold following treatment of mice with levamisole. IL-6
      added in vitro to cells significantly augmented levamisole-induced proliferation
      of liver T cells while anti-IL-6 reduced proliferative activity to control
      levels. These findings suggested that IFN alpha/beta, IL-6, and IL-1 play
      important regulatory roles in controlling the proliferative response of murine
      liver-associated T lymphocytes to levamisole. Finally, the proliferation of bone
      marrow cells was increased in mice given 5-fluorouracil (5FU). On the other hand,
      the proliferation of NPC was dramatically suppressed when 5FU was administered.
      However, the proliferation of these cells was restored when levamisole was given
      after 5FU.

PMID- 9024508
TI  - Autoantibody to p185erbB2/neu oncoprotein by vaccination with xenogenic DNA.
AB  - The passive transfer of antibodies and vaccination procedures against p185, the
      erbB2/neu oncoprotein, are approaches being explored for treatment of human
      breast cancer. We now report the possibility of using the erbB2/neu gene as an
      immunogen. This study demonstrates that intramuscular or intradermal injections
      of rat neuNT full-length DNA into mice generate anti-p185 autoantibodies. Anti
      p185 polyclonals were also shown to bind the homologous human receptor ErbB2 and
      to stain specimens of breast adenocarcinoma from both neu-transgenic mice and
      humans. Further, in vitro assays demonstrated that anti-p185 IgG (probably
      dependent on CD4+ Th1) were able to inhibit human SKBR3 tumour cell growth and to
      mediate their lysis by natural killer cells. The continuous presence of
      circulating neu autoantibodies in mice did not cause any discernible toxic
      effects on normal tissues expressing low levels of self-antigen, even after 1
      year. The experiments reported here raise the possibility that boosting anti
      ErbB2 immunity by DNA vaccination will not induce harmful autoimmunity in humans.

PMID- 9024509
TI  - Undifferentiated rhabdomyosarcoma with lymphoid phenotype expression.
AB  - Poorly differentiated rhabdomyosarcomas are traditionally distinguished from
      lymphomas by their absence of lymphoid markers such as immunoglobulin or CD20
      expression. We have encountered three alveolar rhabdomyosarcomas that were
      initially diagnosed as lymphoid neoplasms because of the expression of a
      lymphocytic phenotype in morphologically undifferentiated tumor cells. Subsequent
      cytogenetic analysis revealed a t(2; 13) in two cases. All cases recurred in the
      chest wall and showed positivity for muscle markers, such as muscle-specific
      actin, myoglobin, MyoD1, and/or desmin on subsequent immunohistochemistry. The
      findings in these three cases lead us to conclude that the presence of a lymphoid
      phenotype does not absolutely exclude the diagnosis of rhabdomyosarcoma.

PMID- 9024510
TI  - Intraoperative search for neuroblastoma by MIBG and radioguided surgery with the
      gamma detector.
AB  - Administration of a tumour-seeking compound labeled with a low-energy isotope and
      intraoperative screening with the gamma probe (radioguided surgery, RGS) could be
      useful in reoperations for advanced neuroblastoma when the normal anatomy is
      altered. A pilot study was performed to test the feasibility of this technique.
      Five patients underwent six relaparotomies for recurrent stage III or IV
      neuroblastoma. All had been treated with intensive chemotherapy and/ or
      metaiodobenzylguanidine (MIBG)-I131 with or without hyperbaric oxygen.
      Reoperation was performed to achieve near-total (greater than 95%) excision. In
      all instances, active tumour was seen on the preoperative MIBG scan. Before the
      operation, a tracer dose of MIBG-I123 was given. At laparotomy, a search was made
      with the gamma probe for areas of increased activity. The gamma probe correctly
      identified active neuroblastoma tissue that was seen on the preoperative MIBG
      scan. There appeared to be a relationship between intensity of radioactivity and
      degree of maturation on histologic examination. This pilot study shows that RGS
      with MIBG and intraoperative use of the gamma probe is able to identify recurrent
      neuroblastoma. Whether this method is able to detect occult tumour and whether
      RGS will result in better outcome are the subjects of ongoing research.

PMID- 9024511
TI  - Clinical characteristics of small functioning adrenocortical tumors in children.
AB  - Twenty of 67 children registered on the International Registry of Childhood
      Adrenocortical Tumors between May 1988 and December 1994 had small adrenocortical
      tumors (defined for this study as measuring < or = 200 cm3 and/or weighing < or =
      100 g). We reviewed the records of these 20 patients to characterize the clinical
      and pathologic findings and outcomes of children with small adrenocortical
      tumors. Median patient age was 2 years (range, 4 months to 5 years). There was
      only one boy. All had clinical signs of virilization, and seven had signs or
      symptoms of Cushing syndrome. A median 5.5 months (range, 1-40 months) had
      elapsed between the first signs of endocrine dysfunction and diagnosis. All
      tumors were surgically resected. Tumor volume was 3.3-195 cm3 (median, -8.7 cm3),
      and weight was 3.7-100 g (median, 36 gm Tumor samples were histologically
      reviewed in 18 cases. Eight were adenomas, and 10 were carcinomas (6 low grade
      and 4 high grade). Pathology records described tumor with diagnostic features of
      adrenocortical carcinoma in two patients. One patient received mitotane for 8
      months after surgery. Only one patient had recurrent disease, which was detected
      6 months after diagnosis and proved rapidly fatal. Another has been lost to
      follow-up. The remaining 18 patients are alive with no evidence of disease at a
      median 2.3 years (range, 6 months to 6.1 years) after diagnosis. Our data suggest
      that children with small adrenocortical tumors have an excellent prognosis with
      surgery as the sole therapy, regardless of tumor histiotype.

PMID- 9024512
TI  - Prognostic significance of chemotherapy dosage characteristics in children with
      osteogenic sarcoma.
AB  - High-dose methotrexate (HDMTX), adriamycin (ADR), and cisplatinum (CDDP) are
      effective agents in the treatment of osteogenic sarcoma (OS). Individual patient
      doses are determined by prior successful clinical trials but may be reduced due
      to ongoing toxicities. It is unknown whether individualized dose reductions of
      these drugs influence disease outcome. We retrospectively studied 27
      consecutively enrolled children treated with HDMTX, ADR, and CDDP as adjuvant
      chemotherapy for OS, for correlations between disease outcome and several
      characteristics of drug dosings the cumulative MTX, CDDP, and ADR doses
      administered and the mean MTX blood levels for each patient. With a median follow
      up of 59 months, the actuarial overall and disease-free survival rates were 70%
      and 59%, respectively. Factors which favorably influenced prognosis on univariate
      analysis were a cumulative ADR dose of > 300 mg/m2 (P = 0.0002) and a cumulative
      MTX dose > 114 gm/m2 (P = 0.0048). By multivariate analysis only the cumulative
      ADR dose > 300 mg/m2 retained prognostic value. We conclude that adjuvant
      chemotherapy dosages may need to be adjusted for therapeutic efficacy in addition
      to adjustments made for toxicity. The effect of different cumulative HDMTX and
      ADR dosages on prognosis in osteosarcoma patients needs to be evaluated in a
      prospective trial.

PMID- 9024513
TI  - Severe humoral hypercalcemia in primary isolated non-Hodgkin's lymphoma of the
      heart.
AB  - The etiology of hypercalcemia was investigated in a patient with primary isolated
      non-Hodgkin's lymphoma of the heart. There was no evidence of bone involvement,
      and parathyroid hormone and calciterol levels were suppressed. Plasma parathyroid
      hormone-related protein (PTHrP 1-86) detected by immunoradiometric assay was
      increased (15 pmol/l compared with < 0.3 pmol/l in a control). We demonstrated
      that PTHrP was the humoral mediator of severe hypercalcemia in our patient.

PMID- 9024514
TI  - Benign proliferative lesions mimicking recurrence of Hodgkin's disease.
AB  - Salvage treatment in patients with recurrent Hodgkin's disease is more effective
      when tumor burden is minimal. That is why more intensive follow-up strategies,
      including frequent imaging tests, have been recently developed for the detection
      of early relapse. However, as screening procedures become more sensitive, there
      is an increasing risk of false-positive results, demonstrating nonmalignant
      proliferative disorders. We describe three young patients who had lymphocyte
      predominant or mixed-cellularity Hodgkin's disease and were in clinical complete
      remission for 2.5-3 years after a combined treatment with chemotherapy and
      radiation. Imaging tests revealed new gallium-avid lymphadenopathy in the chest
      in two cases. Pathologically enlarged pelvic lymph nodes were identified in
      another case, after a diagnosis of recurrent disease in axilla. Those findings
      were interpreted as relapse, and the patients underwent thoracotomy and
      laparotomy, respectively, for histologic confirmation. The results showed
      progressively transformed germinal centers and sarcoid-like lesions, two benign
      proliferative disorders. When patients with Hodgkin's disease in remission show
      new lymphadenopathy, even with positive gallium scan, it seems mandatory to
      obtain tissue for histologic examination, even through invasive procedures such
      as laparotomy and thoracotomy, to avoid wrong diagnosis and unnecessary
      treatment.

PMID- 9024515
TI  - Safety of early hospital discharge of selected febrile children and adolescents
      with cancer with prolonged neutropenia.
AB  - PROBLEM: The safety of early hospital discharge (i.e., before the absolute
      neutrophil count [ANC] exceeds 500 cell/mm3) of febrile neutropenic children and
      adolescents with cancer who had experienced prolonged neutropenia (i.e., for more
      than 7 days) following admission has not been studied. METHOD OF STUDY: Three
      hundred and thirty nine consecutive admissions of children and adolescents with
      cancer for management of febrile neutropenia were reviewed. Early discharge
      criteria included absence of fever for 24 hours prior to discharge, sterile blood
      cultures for 24 hours, evidence of bone marrow recovery defined as a sustained
      increase in platelet count and ANC or absolute phagocyte count (APC), and control
      of local infection if present. Children hospitalized with febrile neutropenia who
      remained neutropenic for more than 7 days were analyzed to assess their outcomes
      following discharge it they had met criteria for early hospital discharge.
      RESULTS: Thirty-three patients in whom neutropenia had persisted for more than 7
      days were discharged before attaining an ANC greater than 500/mm3 when they met
      the early discharge criteria. Only two children (6%) required readmission for
      recurrent fever, a rate which was not different from that of patients discharged
      after a more transient episode of neutropenia (2 of 33 vs. 3 of 121, P = 0.3).
      Both patients who were readmitted had a source of local infection which worsened
      despite oral antibiotics. Both patients appeared clinically well at the time of
      readmission and had sterile cultures during their second hospitalization with
      resolution of local infection. CONCLUSION: This study confirms that low-risk
      criteria used to select children with cancer for discharge before complete
      resolution of neutropenia can be safely applied to those patients whose
      neutropenia lasted more than 7 days following admission.

PMID- 9024516
TI  - Efficacy of a vancomycin solution to prevent bacteremia associated with an
      indwelling central venous catheter in neutropenic and non-neutropenic cancer
      patients.
AB  - We evaluated the efficacy of a vancomycin solution in the prevention of
      bacteremia caused by vancomycin-sensitive organisms (VSO) in cancer patients with
      a tunneled central venous catheter (CVC). Eighty-three patients who had a single
      lumen CVC were randomized to use a heparin solution (25 U/ml) for daily catheter
      flush with (HepVan) or without (Hep) vancomycin, 25 mcg/ml. Febrile episodes were
      recorded, and central and peripheral blood cultures were drawn before beginning
      antibiotic therapy. Patients participated in follow-up to 16,677 catheter days
      (8,666 Hep and 8,011 HepVan), and 143 febrile episodes were recorded (82 Hep and
      61 HepVan). Forty-four episodes of bacteremia occurred, 23 of them due to VSO (16
      occurred in the Hep group and 7 in the HepVan group (P = 0.19). VSO bacteremia
      occurred in 14 neutropenic (absolute neutrophil count < 500 x 10(9)/l) episodes
      (7 Hep vs. 7 HepVan) and in 9 non-neutropenic episodes (9 Hep vs. O HepVan; P =
      0.013). Vancomycin effectively prevented bacteremia by VSO in non-neutropenic
      patients, supporting the idea that intraluminal colonization of indwelling CVCs
      contributes to bacteremia only in these patients.

PMID- 9024517
TI  - Metastatic renal cell carcinoma in a child: 11-year disease-free survival
      following surgery.
AB  - A child with metastatic renal cell carcinoma (RCC) is presented. This case is
      unusual in that the patient has remained disease free for 11 years following
      surgery and only one course of chemotherapy prior to thoracotomy. The management
      of metastatic RCC is reviewed and the genetic mechanisms leading to its
      development briefly discussed.

PMID- 9024518
TI  - Use of micronutrients and alternative drugs by children with acute lymphoblastic
      leukemia.
AB  - The use of alternative therapies is thought to be common among cancer patients.
      To clarify the popularity of micronutrients among children with cancer, we
      performed a controlled follow-up survey. The use of micronutrients and
      alternative drugs by 15 families of children with acute lymphoblastic leukemia
      (ALL) receiving chemotherapy (62 members) and 26 control families (106 members)
      was monitored by means of daily diaries from November 1987 to December 1989.
      Forty percent of children with ALL (6 of 15) and 7.7% of their controls (2 of 26)
      took alternative medicines, the usage among the children with ALL being
      statistically significantly more common (difference, 32.3%; 95% confidence
      interval for difference [CI] 7.1, 57.5%; P < 0.04). All children with ALL and
      50.0% of the control children (13 of 26) took vitamins (difference, 50.0%; 95%
      CI, 20.4-79.6%; P < 0.01). A total of 27.7% of the other members of the ALL
      families (13 of 47) and 11.1% of their counterparts in the control families (10
      of 90) took alternative medicines, the usage in the index families being
      statistically significantly more common (difference, 16.6%; 95% CI, 3.4-29.7%; P
      < 0.03). The malignancy increased the use of alternative medicines among all
      members of the family and of vitamins and trace elements among the affected
      children.

PMID- 9024519
TI  - Acute lymphoblastic leukemia presenting with typhlitis.
AB  - We report an unusual case of acute lymphoblastic leukemia (ALL) that presented as
      right lower quadrant pain in a 17-year-old boy. Ultrasonographic findings were
      consistent with typhlitis. The clinical and imaging symptoms resolved upon
      treatment with antibiotics and conservative care, only to recur after initiation
      of chemotherapy. Familiarity with the clinical presentation and imaging findings
      of typhlitis is important for its correct diagnosis and management.

PMID- 9024520
TI  - Successful management with interferon alpha-2a after prednisone therapy failure
      in an infant with a giant cavernous hemangioma.
AB  - A giant cavernous hemangioma of the left arm with severe thrombocytopenia and
      consumptive coagulopathy was observed in a neonate. Initial treatment with
      prednisone, platelet transfusions, and clotting replacement failed to control the
      bleedings. The child was then treated with daily subcutaneous infusions of
      interferon alpha-2a. Coagulopathy rapidly improved and transfusions were
      drastically reduced. The hemangioma regressed progressively and disappeared after
      4 months of treatment.

PMID- 9024521
TI  - Malignant peripheral nerve sheath tumor arising in a "de novo" ganglioneuroma: a
      case report and review of the literature.
AB  - A case of a "de novo" ganglioneuroma showing a large area of malignant peripheral
      nerve sheath tumor (MPNST) is described. The tumor arose in an 11.5-year-old girl
      with neither stigmata nor family history of von Recklinghausen's
      neurofibromatosis. In addition, the patient had no previous history of a
      neuroblastoma or radiation therapy. This report provides new evidence that,
      although rare, the spontaneous development of an MPNST in a benign ganglioneuroma
      can occur. Immunohistochemical and electron microscopy studies supported the
      finding that the spindle cell component was of nerve sheath origin.

PMID- 9024522
TI  - Implantation metastasis of primary malignant rhabdoid tumor of the brain in an
      adult (one case report).
AB  - Primary malignant rhabdoid tumor (PMRT) of the brain is a rare and recently
      described neoplasm of youth. We report magnetic resonance imaging (MRI), computed
      tomography (CT), and pathology of one case of PMRT in an adult which seeded along
      the needle track for stereotactic biopsy.

PMID- 9024523
TI  - Brain atrophy in children undergoing systemic chemotherapy for extracranial solid
      tumors.
AB  - It has been shown that intrathecal chemotherapy may cause brain damage, which can
      be depicted in neuroimaging studies. The aim of this work was to examine possible
      morphologic alterations in the brain of children with extracranial solid tumors,
      without CNS complications, treated with systemic chemotherapy. Brain CT images of
      69 children with extracranial malignancies were reviewed and the extent of 12 CSF
      compartments was measured in 49 CT examinations performed during intravenously
      given chemotherapy and in 20 after therapy completion. Measurements were compared
      with corresponding normative data. About half of the children undergoing
      chemotherapy and half of the patients examined after treatment were found to have
      diffuse brain atrophy. Focal lesions that might be associated with therapy
      toxicity were not observed. Chemotherapy, even when administered via the systemic
      route, may cause brain damage, which is observed long after the end of treatment.

PMID- 9024524
TI  - The sign of Leser-Trelat.

PMID- 9024525
TI  - Haematologic toxicity during craniospinal irradiation--the impact of prior
      chemotherapy.

PMID- 9024526
TI  - Nephron sparing surgery for unilateral Wilms' tumor.

PMID- 9024527
TI  - Tropisetron in the prevention of nausea and vomiting in 131 children receiving
      cytotoxic chemotherapy.

PMID- 9024554
TI  - A new face for an old syndrome.

PMID- 9024555
TI  - Smith-Lemli-Opitz syndrome diagnosed in a 130-year-old anatomical specimen.
AB  - The Museum Vrolik collection of human anatomy comprises 360 recently re-described
      specimens with congenital anomalies. The external findings in one of these
      specimens, originally described by Willem Vrolik (1801-1863) 130 years ago, were
      suggestive of Smith-Lemli-Opitz (SLO) syndrome. Cholesterol synthesis was
      analyzed in skin biopsies, obtained from the suspected SLO specimen and a control
      specimen. The cholesterol levels in the SLO specimen and in the control specimen
      were in the proportion of 1 to 45. This confirms the diagnosis in this specimen
      which, to our knowledge, represents the oldest known case of SLO syndrome.

PMID- 9024556
TI  - Smith-Lemli-Opitz syndrome: thirty-year follow-up of "S" of "RSH" syndrome.
AB  - We have reassessed patient "S," one of the first 3 individuals recognized to have
      Smith-Lemli-Opitz (or RSH) syndrome, at age 34 years, and we describe his
      physical, developmental, and behavioral manifestations. This reassessment
      provides formal evidence that this individual has the cholesterol biosynthetic
      defect which is thought to be the cause of Smith-Lemli-Opitz syndrome. Dietary
      manipulation appears to have had a beneficial effect on the patient's behavior
      and suggests that even in adults with this condition, dietary cholesterol
      supplementation may be indicated.

PMID- 9024557
TI  - Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome
      and abnormal cholesterol metabolism.
AB  - RSH/Smith-Lemli-Opitz (RSH/SLO) syndrome is an autosomal recessive malformation
      syndrome recently shown to be associated with a severe deficiency of cholesterol
      biosynthesis and markedly elevated plasma and tissue levels of 7
      dehydrocholesterol (7-DHC), the immediate precursor of cholesterol in the
      Kandutsch-Russell biosynthetic pathway. Because these biochemical abnormalities
      permit a reassessment of RSH/SLO on biochemical criteria rather than less
      specific physical criteria, we review here the clinical and biochemical
      characteristics of our first 80 patients with abnormally increased levels of 7
      DHC. The study population included 68 index patients and 12 additional relatives
      identified by quantification of 7-DHC and cholesterol in plasma, amniotic fluid,
      or cultured fibroblasts, lymphoblasts, or amniocytes. As demonstrated in other
      clinical syndromes when redefined biochemically, we have found a wider range of
      clinical expression of RSH/SLO than previously recognized. These newly recognized
      atypical RSH/SLO patients included several with no malformations other than
      syndactyly of the toes and, at the other extreme, patients with frank
      holoprosencephaly or multiple visceral anomalies who died in utero. Syndactyly of
      toes 2 and 3 was the most common malformation, occurring in all but one of 80
      patients. The best biochemical predictor of clinical severity was the plasma
      cholesterol level, which decreased with increasing clinical severity. However, at
      least 10% of patients, including one newborn infant, had normal cholesterol
      levels at the time of diagnosis and would have been missed without specific
      quantification of 7-DHC. Not unexpectedly, several patients carrying a clinical
      diagnosis of RSH/SLO were found to have normal levels of all plasma sterols and
      apparently normal cholesterol biosynthesis in cultured cells. A comparison of the
      frequency of anomalies in our biochemically identified patients with similar data
      from previously reported clinical series suggests that up to 25% of reports of
      RSH/SLO in the literature may describe genetic conditions other than RSH/SLO with
      7-DHC-emia.

PMID- 9024558
TI  - Cardiovascular malformations in Smith-Lemli-Opitz syndrome.
AB  - We reviewed 215 patients (59 new, 156 from the literature) with Smith-Lemli-Opitz
      syndrome (SLOS), and found that 95 (44%) had a cardiovascular malformation (CVM).
      Classifying CVMs by disordered embryonic mechanisms, there were 5 (5.3%) class 1
      (ectomesenchymal tissue migration abnormalities), 56 (58.9%) class II (abnormal
      intracardiac blood flow), 25 (26.3%) class IV (abnormal extracellular matrix),
      and 5 (5.3%) class V (abnormal targeted growth). Comparing the frequencies of
      individual CVMs in this series with a control group (the Baltimore-Washington
      Infant Study), there were 6 individual CVMs which showed a significant difference
      from expected values. When frequencies of CVMs in SLOS were analyzed by
      mechanistic class, classes IV and V were significantly more frequent, and class I
      significantly less frequent, than the control group. Although CVMs in SLOS
      display mechanistic heterogeneity, with an overall predominance of class II CVMs,
      the developmental error appears to favor alteration of the cardiovascular
      developmental mechanisms underlying atrioventricular canal and anomalous
      pulmonary venous return. This information should assist the clinical geneticist
      evaluating a patient with possible SLOS, and should suggest research direction
      for the mechanisms responsible for the SLOS phenotype.

PMID- 9024559
TI  - Physical mapping of the chromosome 7 breakpoint region in an SLOS patient with
      t(7;20) (q32.1;q13.2).
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder
      characterized by multiple congenital anomalies and mental retardation. SLOS has
      an associated defect in cholesterol biosynthesis, but the molecular genetic basis
      of this condition has not yet been elucidated. Previously our group reported a
      patient with a de novo balanced translocation [t(7;20)(q32.1;q13.2)] fitting the
      clinical and biochemical profile of SLOS. Employing fluorescence in situ
      hybridization (FISH), a 1.8 Mb chromosome 7-specific yeast artificial chromosome
      (YAC) was identified which spanned the translocation breakpoint in the reported
      patient. The following is an update of the on-going pursuit to physically and
      genetically map the region further, as well as the establishment of candidate
      genes in the 7q32.1 breakpoint region.

PMID- 9024560
TI  - Sterol concentrations in cultured Smith-Lemli-Opitz syndrome skin fibroblasts:
      diagnosis of a biochemically atypical case of the syndrome.
AB  - The Smith-Lemli-Opitz syndrome is a common birth defect syndrome caused by a
      deficiency of 7-dehydrocholesterol delta 7-reductase, an essential enzyme in the
      biosynthesis of cholesterol. The syndrome can usually be diagnosed easily from
      the plasma markers of markedly elevated 7-dehydrocholesterol and reduced
      cholesterol concentrations. However, atypical cases with normal plasma levels of
      cholesterol with only moderately elevated 7-dehydrocholesterol have been
      reported. To establish a sensitive method for the biochemical diagnosis of the
      atypical cases of the syndrome, we measured sterol concentrations of cultured
      skin fibroblasts. 7-Dehydrocholesterol concentrations in patients' fibroblasts
      grown in the presence of 10% fetal bovine serum were significantly higher than
      those in controls and parents (P < 0.0005), but they were not elevated
      proportionately as much as in plasma. To re-produce the accumulation of 7
      dehydrocholesterol, the cells were exposed to delipidated medium to induce sterol
      biosynthesis. After 4 weeks, 7-dehydrocholesterol concentrations in patients'
      fibroblasts increased from 2.8 +/- 0.3% to 34 +/- 3% of total sterols
      (cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol). The increase was
      also observed in fibroblasts from an atypical patient who has a normal plasma
      cholesterol level and a 7-dehydrocholesterol concentration of only 0.15 mg/dl. In
      contrast, cells from parents and controls accumulated very little 7
      dehydrocholesterol (< 1% of total sterols). These results demonstrate that
      cultured fibroblasts exhibit abnormally high accumulation of 7-dehydrocholesterol
      after cells are exposed to delipidated medium not only in typical patients, but
      also in an atypical case. The present method is a sensitive procedure for the
      biochemical diagnosis of this syndrome.

PMID- 9024561
TI  - Screening for abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz
      syndrome: rapid determination of plasma 7-dehydrocholesterol by ultraviolet
      spectrometry.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is a common condition caused by deficiency
      of 7-dehydrocholesterol delta 7-reductase. The syndrome can usually be diagnosed
      by demonstrating markedly increased plasma concentrations of the cholesterol
      precursor, 7-dehydrocholesterol. We describe a simple and rapid method for
      detection of plasma 7-dehydrocholesterol by use of ultraviolet (UV) spectrometry.
      Lipids were extracted from plasma by addition of ethanol and n-hexane, and the n
      hexane phase was directly subjected to spectrometry. The absorption maxima
      characteristics of 7-dehydrocholesterol (lambda max 271, 282, and 294 nm) were
      observed in patients' plasma but not in controls. For quantitative measurements,
      absorbance at 282 nm was used. Since this absorbance is the sum of the absorbance
      derived from 7-dehydrocholesterol and background absorbance, the concentrations
      of 7-dehydrocholesterol in various plasma samples were quantified by subtracting
      estimated background absorbance at 282 nm from observed absorbance at 282 nm. The
      results correlated well with total (free plus esterified) 7-dehydrocholesterol
      concentrations measured by gas-liquid chromatographic method. The UV
      spectrometric assay was sensitive enough to detect increased 7-dehydrocholesterol
      in cultured skin fibroblasts from patients grown in delipidated medium. The
      present method will make it possible to screen plasma or fibroblasts to detect
      the syndrome rapidly in general clinical laboratories.

PMID- 9024562
TI  - Increased expression of low-density lipoprotein receptors in a Smith-Lemli-Opitz
      infant with elevated bilirubin levels.
AB  - We report on an infant girl with severe RSH or Smith-Lemli-Opitz syndrome with
      hyperbilirubinemia. The infant died at age 2 months. Sterol analysis of liver and
      brain tissues showed marked elevations of 7-dehydrocholesterol with decreased
      levels of cholesterol. Immunocytochemical analysis demonstrated remarkable
      increases in low-density lipoprotein (LDL) receptors in these tissues, indicative
      of a deficiency in available cholesterol for tissue needs.

PMID- 9024563
TI  - Direct analysis of filter paper blood specimens for identification of Smith-Lemli
      Opitz syndrome using time-of-flight secondary ion mass spectrometry.
AB  - In this study, time-of-flight secondary ion mass spectrometry was used to
      distinguish between blood of normal infants and that of individuals with Smith
      Lemli-Opitz (SLO) syndrome. SLO syndrome results in an abnormally low
      concentration of blood cholesterol and an elevated concentration of 7
      dehydrocholesterol. Blood was spotted on filter paper and analyzed directly with
      no extractions or separations. Results showed that using ratios of fragment ions
      for cholesterol/dehydrocholesterol, patients with SLO and normal individuals
      could be unambiguously distinguished. Unknown samples from 28 individuals were
      obtained and identified correctly.

PMID- 9024564
TI  - Clinical effects of cholesterol supplementation in six patients with the Smith
      Lemli-Opitz syndrome (SLOS)
AB  - We describe the clinical effects of cholesterol supplementation in 6 children
      with the RSH-"Smith-Lemli-Opitz" syndrome (SLOS). The children ranged in age from
      birth to 11 years at the onset of therapy, with pretreatment cholesterol levels
      ranging from 8 to 62 mg/dl. Clinical benefits of therapy were seen in all
      patients, irrespective of age at onset of treatment, or severity of cholesterol
      defect. Effects of treatment included improved growth, more rapid developmental
      progress, and a lessening of problem behaviors. Pubertal progression in older
      patients, a better tolerance of infection, improvement of gastrointestinal
      symptoms, and a diminution in photosensitivity and skin rashes were also noted.
      There were no adverse reactions to treatment with cholesterol. This preliminary
      study suggests that cholesterol supplementation may be of benefit to patients
      with the SLOS.

PMID- 9024565
TI  - Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial.
AB  - Patients with the RSH or Smith-Lemli-Optiz syndrome (SLOS) have an inborn error
      of cholesterol biosynthesis which results in a deficiency of cholesterol and an
      elevation of the cholesterol precursor, 7-dehydrocholesterol. A treatment
      protocol consisting of administration of cholesterol +/- bile acids was initiated
      in an attempt to correct the biochemical abnormalities seen. Fourteen patients (8
      female, 6 male: ages 2 months to 15 years) have now been treated for 6-15 months.
      Three patients received cholesterol alone, while 11 patients received cholesterol
      and one or more bile acids. Biochemical improvement in sterol levels and in the
      ratio of cholesterol to total sterols was noted in all patients. The most marked
      improvement was noted in patients presenting with initial cholesterol levels < 40
      mg/dl. No toxicity was observed. Clinical improvement in growth and
      neurodevelopmental status was also observed.

PMID- 9024566
TI  - Cholesterol and bile acid replacement therapy in children and adults with Smith
      Lemli-Opitz (SLO/RSH) syndrome.
AB  - Tint et al. [N Engl J Med 1994, 330:107-113], working with blood samples from the
      Smith-Lemli-Opitz syndrome (SLOS) patients of Irons and Elias showed the
      biochemical basis of this disorder to be a cholesterol biosynthesis defect [Irons
      et al., Lancet, 1993, 341:1414]. Based on this finding, clinical protocols for
      cholesterol and bile acid replacement therapy were established in a few centers
      including the University of Pittsburgh. We report our experience with bile acid
      and/or cholesterol replacement therapy in six patients with SLOS, now aged 3-27
      years, with a confirmed biochemical diagnosis. Levels of plasma cholesterol and 7
      dehydrocholesterol were correlated with periodic clinical evaluations over 8-27
      months of therapy. There was a marked improvement in the growth of all the
      children. There was also an increase in the plasma cholesterol level in all the
      children and an overall increase in their percent sterol as cholesterol.
      Subjective improvement was also noted in their development. Although there was no
      significant change in the plasma cholesterol level of the older patients, there
      was a marked improvement in their behavior and in their quality of life.

PMID- 9024567
TI  - Smith-Lemli-Opitz syndrome produced in rats with AY 9944 treated by intravenous
      injection of lipoprotein cholesterol.
AB  - A limitation to treating Smith-Lemli-Opitz infants by giving dietary cholesterol
      is their impaired ability to absorb cholesterol due to a deficiency of bile
      acids. Since intravenously administered lipoprotein cholesterol should not
      require bile acids for uptake into tissues, we tested the effects of this form of
      cholesterol on tissue cholesterol and 7-dehydrocholesterol levels in an animal
      model of SLO, created by feeding rats 0.02% AY 9944. Intravenous administration
      of 15 mg of bovine cholesterol supertrate twice daily increased serum cholesterol
      levels from 11 to over 250 mg/dl. This treatment increased liver cholesterol
      levels from 309 to over 900 micrograms/g and lowered hepatic 7-dehydrocholesterol
      levels from 1546 to 909 micrograms/g. A combination of iv cholesterol and 2%
      dietary cholesterol was most effective as it raised hepatic cholesterol levels to
      1950 micrograms/g, which is 50% above normal. 7-Dehydrocholesterol levels were
      decreased to 760 micrograms/g. Similar responses were seen for heart, lung,
      kidney, and testes. Brain sterol levels were not significantly affected. AY 9944
      caused a modest increase in hepatic HMG-CoA reductase activity. Administration of
      dietary cholesterol together with iv cholesterol lowered hepatic HMG-CoA
      reductase activity to barely detectable levels. The data indicate that the
      combination of iv and dietary cholesterol was most effective in raising
      cholesterol levels, lowering 7-dehydrocholesterol levels, and inhibiting de novo
      cholesterol biosynthesis.

PMID- 9024568
TI  - Pathogenesis of malformations in a rodent model for Smith-Lemli-Opitz syndrome.
AB  - The fact that Smith-Lemli-Opitz syndrome (SLOS), a syndrome comprising major
      malformations involving a number of organ systems, results from an abnormality in
      cholesterol biosynthesis, was discovered only recently. Utilizing a drug (BM
      15.766) to inhibit the same step in cholesterol biosynthesis as is abnormal in
      those affected with SLOS, we have developed a rat model that presents with
      abnormalities observed as early as gestational day 12 that appear to be
      consistent with some of those subsequent malformations that comprise the human
      syndrome. Abnormalities of the brain and face include deficiency in the midline
      region of the upper face, narrowing of the forebrain hemispheres and of the
      cerebral aqueduct, and deficiency in the developing lower jaw. Associated
      pathogenesis, as observed on gestational day 11 in histological sections and with
      scanning electron microscopy, involves abnormal cell populations at the rim of
      the developing forebrain and in the alar plate of the lower midbrain and hind
      brain. The affected cells appear abnormally rounded up, having apparently lost
      their normal cell contacts. The potential basis for the selective vulnerability
      of this cell population and the impact of its vulnerability relative to
      subsequent dysmorphogenesis is discussed.

PMID- 9024569
TI  - Giant-cell chondrodysplasia in a male infant with clinical and radiological
      findings resembling the Piepkorn type of lethal osteochondrodysplasia.
AB  - We report on a patient whose clinical, radiologic, and histopathologic findings
      are compatible with the Piepkorn type of lethal short-limb osteochondrodysplasia,
      but who also showed multinucleated giant chondrocytes in cartilage.
      Multinucleated giant cells are an unusual finding in osteochondrodysplasias,
      having been reported in atelosteogenesis type I and boomerang dysplasia. This
      uncommon histopathologic finding and the clinical and radiographic findings
      strongly support the diagnosis of boomerang dysplasia in the present patient. Our
      patient supports the previously suggested existence of an entity including
      atelosteogenesis and boomerang dysplasia. If this is so, the current patient and
      that described by Piepkorn et al. [1977: Teratology 16:345-350] could represent
      the most severe clinical expression of that condition.

PMID- 9024570
TI  - New MCA/MR syndrome with generalized hypotonia, congenital hydronephrosis, and
      characteristic face.
AB  - We have observed a newly recognized syndrome in two unrelated Japanese patients.
      Manifestations include severe mental retardation, growth failure, generalized
      floppiness, congenital hydronephrosis, cardiac anomalies, cleft palate, and
      characteristic face. To date, caused genesis is unknown.

PMID- 9024571
TI  - Bilateral sensorineural deafness and hydrocephalus due to foramen of Monro
      obstruction in sibs: a newly described autosomal recessive disorder.
AB  - We identified a Canadian-Mennonite family in which a brother and sister have
      hydrocephalus due to obstruction at the foramen of Monro and profound bilateral
      sensorineural deafness. This appears to be a unique combination of anomalies and,
      to our knowledge, has not been reported previously. Both parents and a brother
      are phenotypically normal. The parents are second cousins. Thus, on the basis of
      consanguinity, affected sibs of both sexes, and in the absence of evidence for
      intrauterine infections or other adverse perinatal events, this syndrome is
      likely inherited in an autosomal recessive fashion.

PMID- 9024572
TI  - Becker nevus syndrome.
AB  - The new term Becker nevus syndrome is proposed for a phenotype characterized by
      the presence of a particular type of organoid epithelial nevus showing
      hyperpigmentation, increased hairiness and hamartomatous augmentation of smooth
      muscle fibers, and other developmental defects such as ipsilateral hypoplasia of
      breast and skeletal anomalies including scoliosis, spina bifida occulta, or
      ipsilateral hypoplasia of a limb. The present review includes 23 cases that can
      be categorized under this designation. The Becker nevus syndrome usually occurs
      sporadically. The associated anomalies tend to show a definite regional
      correspondence, suggesting a common origin from an early postzygotic mutation.

PMID- 9024573
TI  - An atypical case of Fanconi anemia in elderly sibs.
AB  - We describe a 56-year-old woman suspected of Fanconi anemia on the basis of the
      following clinical findings: microcephaly, short stature, congenital deafness,
      and the clinical findings in her deceased brother. Hematologic or other signs of
      malignancy were absent. The diagnosis was confirmed by demonstrating
      hypersensitivity of her lymphocytes to mitomycin C (MMC). Cell fusion experiments
      indicated that the patient belongs to complementation group A. The patient's
      brother died at the age of 50 of heart and renal failure, and anemia. He had
      clinical findings similar to those of his sister, and a horseshoe kidney. From 31
      years on he had thrombocytopenia and leucopenia. Both patients had insulin
      dependent diabetes mellitus. A chromosomal breakage test carried out elsewhere
      before his death failed to demonstrate MMC hypersensitivity of his lymphocytes,
      which led to the investigation of his sister. To our knowledge these two cases
      are the oldest Fanconi anemia patients reported thus far.

PMID- 9024574
TI  - Brachmann-de Lange syndrome.

PMID- 9024575
TI  - Clinical and locus heterogeneity in brachydactyly type C.
AB  - Brachydactyly type C is characterized by shortness of the second and fifth middle
      phalanges and the first metacarpal. It is inherited as an autosomal dominant
      trait, and is noted for its widely variable clinical phenotype both within and
      between families. In most families involvement is limited to the hands. However,
      in some families additional skeletal and non-skeletal findings have been
      reported. We report on 12 affected members from a 5 generation kindred that
      segregates a brachydactyly type C phenotype. All affected individuals had
      shortness principally affecting the second and fifth phalanges and first
      metacarpal. However, the metacarpal-phalangeal profile indicated that other
      digital elements were short as well. In addition, one affected individual had a
      bilateral Madelung deformity, but none had foot involvement. No other non
      skeletal findings cosegregated with brachydactyly in this family. Recently, a
      gene for brachydactyly type C has been localized to 12q24. This was done by
      studying a large kindred first reported by Haws [1963], which manifests both hand
      and foot anomalies. Here we present linkage data which excludes the 12q24 locus
      in our kindred, indicating locus heterogeneity as one explanation for the
      interfamilial variability described in brachydactyly type C.

PMID- 9024576
TI  - European Gene Mapping Project (EUROGEM): breakpoint panels for human chromosomes
      based on the CEPH reference families. Centre d'Etude du Polymorphisme Humain.
AB  - Meiotic breakpoint panels for human chromosomes 2, 3, 4, 5, 6, 7, 8, 9, 10, 13,
      14, 15, 17, 18, 20 and X were constructed from genotypes from the CEPH reference
      families. Each recombinant chromosome included has a breakpoint well-supported
      with reference to defined quantitative criteria. The panels were constructed at
      both a low-resolution, useful for a first-pass localization, and high-resolution,
      for a more precise placement. The availability of such panels will reduce the
      number of genotyping experiments necessary to order new polymorphisms with
      respect to existing genetic markers. This paper shows only a representative
      sample of the breakpoints detected. The complete data are available on the World
      Wide Web (URL http:/(/)www.icnet.uk/axp/hgr/eurogem++ +/HTML/data.html) or by
      anonymous ftp (ftp.gene.ucl.ac.uk in/pub/eurogem/maps/breakpoints).

PMID- 9024577
TI  - CROSSFIND: software for detecting and displaying well-characterised meiotic
      breakpoints in human family data.
AB  - An algorithm for detecting well-characterised breakpoints in human family data
      has been developed and implemented as a computer program. The well-established
      program CRI-Map is used to perform the necessary likelihood analysis and generate
      the individual chromosomes, and then a set of user-defined parameters is used to
      detect the breakpoints, sort them by their position and classify them according
      to their support. A further program produces PostScript figures giving a visual
      representation of the breakpoints. The programs can be applied to data from human
      chromosomes, and the resulting breakpoint panels used to place new markers
      rapidly on to the map by typing only a few key individuals and their ancestors. A
      service has been established on the World Wide Web for chromosome 9, allowing
      workers to fill in an on-line form requesting a suitable panel of breakpoints to
      facilitate the mapping of new markers. A key feature of this approach is that all
      of the computing is done whilst detecting the breakpoints, after which new
      markers can be positioned without any need for a computer. CROSSFIND has been
      used to generate all the meiotic breakpoint panels shown in the preceding paper
      by members of the Eurogem Collaboration (Cox et al 1996).

PMID- 9024578
TI  - Site 73 in hypervariable region II of the human mitochondrial genome and the
      origin of European populations.
AB  - The majority of published human mitochondrial DNA sequence data are confined to
      hypervariable region I in the control region. By contrast, this paper focuses on
      a nucleotide site in hypervariable region II. Unlike most non-European
      populations whose mtDNA sequences have been studied in the literature, the
      British 'white Caucasian' population has a high level of variation at site 73
      (following the site numbering by Anderson et al. 1981). This variation appears to
      have its origin largely in a mutation from guanine to adenine at that site with
      an estimated minimum age between 15,000 and 25,000 years. The data of Piercy et
      al. (1993) suggest that roughly half of the British 'white Caucasian'
      mitochondrial gene pool is descended from a common maternal ancestor who carried
      this mutation at site 73. This site also plays a central role in distinguishing
      the five major European mtDNA clusters identified in Richards et al. (1996). We
      suggest that the lineages carrying an A at site 73, together with some other
      lineages, may have their origins in a small founder population which expanded
      after the last glacial maximum about 20,000 years ago. We conclude that, in
      addition to region I sequences, site 73 is worth determining in studies of
      Caucasian populations.

PMID- 9024579
TI  - Apolipoprotein E genotype epsilon 4/epsilon 2 in the STANISLAS Cohort Study-
      dominance of the epsilon 2 allele?
AB  - Apolipoprotein (apo) E has been discussed as a marker for cardiovascular risk,
      but information about lipid traits in healthy individuals having one of the rare
      apoE genotypes (epsilon 4/epsilon 2, epsilon 2/epsilon 2 or epsilon 4/epsilon 4)
      is scarce. Our work was designed to answer the following questions: 1. Are the
      allelic effects of epsilon 2 and epsilon 4 on lipid traits additive or dominant?
      2. If there is additivity, do the allelic effects of epsilon 2 and epsilon 4 have
      the same magnitude? 3. Are the allelic effects neutralised in epsilon 4/ epsilon
      2 individuals who are under the influence of both rare alleles? Allelic effects
      on apoB and apoE serum levels were codominant. Allelic models are thus not
      adequate to study the influence of apoE polymorphism on these traits. Allelic
      effects were additive for total cholesterol, LDL-C, HDL-C and apoAI, with epsilon
      2 having a greater impact than epsilon 4. Serum levels differed significantly
      between epsilon 4/epsilon 2 and epsilon 3/epsilon 3 individuals only for apoE (p
      < 0.001) and for apoB (p < 0.05).

PMID- 9024580
TI  - Similarities in anthropometrical traits of children and their parents in a
      Bulgarian population.
AB  - A study has been made of 36 body and 11 craniofacial measurements in a selected
      sample of 251 Bulgarian families, comprising parents and their children over 15
      years. The mid parent-offspring and correlation coefficients indicate that the
      extent of genetic determination varies considerably from one measurement to
      another. There is an evidence of directional dominance for three body traits and
      for two craniofacial traits. None of the different parent-offspring correlations
      is compatible with X-linked inheritance. A greater maternal than paternal
      influence is evident for biacromial diameter but a greater paternal influence is
      seen for head height, nose height and for ear height and breadth.

PMID- 9024581
TI  - Investigating a single facet of a multilocus model.
AB  - We consider looking a a single locus of a multilocus model, such as that for
      IDDM, in particular the use of the sib-pair method concentrating attention on the
      influence of HLA.

PMID- 9024619
TI  - Regulation of endothelial cell adhesion by profilin.
AB  - BACKGROUND: Although profilin is believed to be an essential regulator of the
      actin cytoskeleton in most cells, its precise role in mammalian cells remains
      unknown. We have used replication-incompetent adenovirus carrying the human
      profilin I cDNA as a means rapidly to increase the concentration of profilin in
      human aortic endothelial cells 12-31-fold above baseline--levels never before
      achieved in mammalian cells. RESULTS: The concentration of filamentous actin was
      not detectably affected by profilin overexpression. Actin stress fibers were,
      however, absent from areas of high profilin content in overexpressing cells, and
      the bulk of filaments was located at the periphery of the cells. We observed a
      gradient in the distribution of overexpressed profilin in migrating endothelial
      cells, with most profilin molecules concentrated near the advancing edge where
      focal contacts are being formed and focal adhesion proteins are located. Profilin
      overexpression resulted in increased recruitment of fibronectin receptors to the
      plasma membrane. Adhesion of endothelial cells to fibronectin was markedly and
      selectively increased by profilin overexpression. CONCLUSIONS: We conclude that
      an important role for profilin in mammalian cells may be its contribution to the
      formation of focal contacts, particularly those involving the fibronectin
      receptor.

PMID- 9024620
TI  - Dynamic microtubules and specification of the zebrafish embryonic axis.
AB  - BACKGROUND: The zebrafish is emerging as an important genetic system for the
      study of vertebrate development, and many zygotic mutations affecting
      embryogenesis have been isolated. The early events in development are under the
      control of maternal genes but are relatively unexplored. Here, the process of
      axis specification is investigated. RESULTS: The vegetal pole of the zygote
      transiently contains a dense array of parallel microtubules, while microtubules
      near the equator are disorganized. Irradiation of the zygote with ultraviolet
      light disrupts the formation of the vegetal microtubule array and causes loss of
      the axis; brief treatment with nocodazole at this stage also causes defects in
      the axis. During cleavage stages, yolk cortical microtubules reorganize to form
      arrays that apparently extend from marginal blastomeres. Prolonged exposure to
      cold (18 degrees C) or incubation in nocodazole prior to the 32-cell stage
      disrupts cortical microtubules and causes premature formation of the yolk
      syncytial layer; these treatments also prevent formation of an axis, as indicated
      by the absence of goosecoid and forkhead2 expression and of translocation of beta
      catenin into nuclei. Cortical microtubule arrays are required for the transport
      of particles from the vegetal hemisphere into marginal blastomeres, as shown by
      the movement of polystyrene beads; treatments that prevent axis formation also
      prevent the entry of beads into blastomeres. CONCLUSIONS: To form an organizer,
      zebrafish blastomeres appear to require substances which are transported from the
      vegetal hemisphere of the yolk cell by cortical microtubules. Initial asymmetry
      appears dependent on an array of parallel microtubules at the vegetal pole.

PMID- 9024621
TI  - Is Pasteur's day past?

PMID- 9024622
TI  - Activation of Pak by membrane localization mediated by an SH3 domain from the
      adaptor protein Nck.
AB  - BACKGROUND: The adaptor protein Nck consists of three Src homology 3 (SH3)
      domains followed by one SH2 domain. Like the Grb2 adaptor protein, which is known
      to couple receptor tyrosine kinases to the small GTPase Ras, Nck is presumed to
      bind to tyrosine-phosphorylated proteins using its SH2 domain and to downstream
      effector proteins using its SH3 domain. Little is known, however, about the
      specific biological function of Nck. The Pak family of serine/threonine kinases
      are known to be activated by binding to the GTP-bound form of Cdc42 or Rac1,
      which are small GTPases of the Rho family that are involved in regulating the
      organization of the actin cytoskeleton. RESULTS: We present evidence that Nck can
      mediate the relocalization and subsequent activation of the Pak1 kinases. We show
      that Nck associates in vivo with Pak using the second of its three SH3 domains,
      and that localization of this individual Nck SH3 domain, or of Pak kinase itself,
      to the membrane results in activation of Pak and stimulation of downstream
      mitogen activated protein kinase cascades. Activation of downstream signaling by
      the membrane-localized Nck SH3 domain is blocked by a kinase-inactive mutant form
      of Pak1. CONCLUSION: These results demonstrate that localization of Pak1 to the
      membrane in the absence of other signals is sufficient for its activation, and
      imply that the Nck adaptor protein could function to link changes in tyrosine
      phosphorylation of cellular proteins to the Cdc42/Pak signaling pathway.

PMID- 9024623
TI  - CD4-independent association between HIV-1 gp120 and CXCR4: functional chemokine
      receptors are expressed in human neurons.
AB  - BACKGROUND: Chemokines are a family of proteins that chemoattract and activate
      immune cells by interacting with specific receptors on the surface of their
      targets. We have shown previously that chemokine receptors including the
      interleukin-8 receptor B (CXCR2) and the Duffy blood group antigen are expressed
      on subsets of neurons in various regions of the adult nervous system. RESULTS:
      Using a combination of immunohistochemical staining and receptor binding studies,
      we show that hNT cells, which are differentiated human neurons derived from the
      cell line NTera2, express functional chemokine receptors of the C-X-X and C-C
      types. These chemokine receptors include CXCR2, CXCR4, CCR1 and CCR5. We
      demonstrate high-affinity binding of both types of chemokines to hNT neurons and
      dose-dependent chemotactic responses to these chemokines in differentiated, but
      no t undifferentiated, NTera 2 cells. In addition, we show that the envelop
      glycoprotein from the T-cell-tropic human immunodeficiency virus 1 (HIV-1) strain
      IIIB is a CD4-independent, dose-dependent inhibitor of the binding of stromal
      cell-derived factor 1 to its receptor, CXCR4. CONCLUSIONS: These data support
      recent findings that members of the chemokine family, including CCR5 and
      LESTR/Fusin (CXCR4), function as coreceptors in combination with CD4 for HIV-1
      invasion. This is the first report of functional expression of chemokine
      receptors on human neurons. Furthermore, our studies provide for direct CD4
      independent association of the viral envelope protein of the HIV-1 strain III
      with the chemokine receptor CXCR4.

PMID- 9024624
TI  - Physical and genetic mapping of the prosaposin gene (PSAP) to bovine chromosome
      28.

PMID- 9024625
TI  - Using SSCP to facilitate mapping microsatellite loci.

PMID- 9024626
TI  - MutS homologs in mammalian cells.
AB  - Alterations of the human mismatch repair genes have been linked to hereditary non
      polyposis colon cancer (HNPCC) as well as to sporadic cancers that exhibit
      microsatellite instability. The human mismatch repair genes are highly conserved
      homologs of the Escherichia coli MutHLS system. Six MutS homologs have been
      identified in Saccharomyces cerevisiae and four MutS homologs have been
      identified in human cells. At least three of these eukaryotic MutS homologs are
      involved in the recognition/binding of mispaired nucleotides and nucleotide
      lesions. MSH2 plays a fundamental role in mispair recognition whereas MSH3 and
      MSH6 appear to modify the specificity of this recognition. The redundant
      functions of MSH3 and MSH6 explain the greater prevalence of hmsh2 mutations in
      HNPCC families.

PMID- 9024627
TI  - Tying loose ends: roles of Ku and DNA-dependent protein kinase in the repair of
      double-strand breaks.
AB  - A convergence of information from biochemistry, yeast and mammalian genetics,
      immunology, and radiation biology has permitted identification of some of the
      protein participants - Ku, DNA-PK, XRCC4 - and the reaction intermediates in DNA
      end joining, suggesting how broken chromosomal ends may be recognized and
      repaired in eukaryotic cells. Some components may be defective in inherited
      disorders.

PMID- 9024628
TI  - Control of cell cycle arrest by the Mec1sc/Rad3sp DNA structure checkpoint
      pathway.
AB  - The Mec1(sc)/Rad3(sp) protein family is central to the checkpoint pathways of
      cells. Functions upstream and downstream of Mec1(sc)/Rad3(sp) show both
      similarities and differences when compared between organisms. Analogy with a
      related protein, DNAPKcs, suggests that different subunits may activate
      Mec1(sc)/Rad3(sp) in response to specific DNA or DNA-protein structures.

PMID- 9024629
TI  - Phosphorylation and proteolysis: partners in the regulation of cell division in
      budding yeast.
AB  - The budding yeast cell cycle oscillates between states of low and high cyclin
      B/cyclin-dependent kinase (CLB/CDK) activity. Remarkably, the two transitions
      that link these states are governed by ubiquitin-mediated proteolysis. The
      transition from low to high CLB activity is triggered by degradation of the
      CLB/CDK inhibitor SIC1, and the complementary excursion is propelled by the
      proteolytic destruction of CLBs. The extracellular environment controls this two
      state circuit by regulating G1 cyclin/CDK activity, which is directly required
      for SIC1 proteolysis. Thus, stable oscillations of chromosome replication and
      segregation in budding yeast are propagated by the interplay between protein
      phosphorylation and protein degradation.

PMID- 9024631
TI  - Stopping and starting the meiotic cell cycle.
AB  - The meiotic cell cycle arrests in response to both perturbations and
      developmental signals. Recent research suggests that meiosis has checkpoints to
      monitor the completion of meiotic recombination and the attachment of chromosomes
      to the spindle. New insights have been gained into how meiosis resumes after
      normal developmental arrests, and new genes have been identified that are
      required for proper meiotic progression.

PMID- 9024630
TI  - Cdks and the Drosophila cell cycle.
AB  - Cyclin-dependent kinases play essential roles in driving the cell cycle. Much
      progress has been made in Drosophila over the past year in identifying the
      specific requirements for individual cyclins in particular cell cycle events.
      These studies encompass many aspects of the cell cycle, from the addition of a G1
      phase to the cell cycle during embryogenesis to the role of cyclin degradation in
      progression through anaphase.

PMID- 9024632
TI  - Retinoblastoma protein in growth suppression and death protection.
AB  - Puzzling new information indicates an inadequacy in our understanding of the
      retinoblastoma protein (RB). RB and the transcription factor E2F appear to be
      collaborators. RB-E2F interaction is necessary but not sufficient for growth
      suppression. Unbecoming of a tumor suppressor, RB has an active role in
      antagonizing the death response. How RB integrates its multiple functions into a
      tumor suppression program is still an open issue.

PMID- 9024633
TI  - p53; from inductive signal to cellular effect.
AB  - During the past year, the story of how p53 suppresses carcinogenesis has
      increased in complexity. Further insight has been provided into the activation of
      latent p53, the biochemical mechanisms involved in growth arrest and apoptosis,
      and the influence of various signals on these cellular effects. Additionally,
      roles for p53 have been described in cell senescence, in suppressing
      teratogenesis, and in processes that may directly contribute to the maintenance
      of genomic stability.

PMID- 9024634
TI  - Pheromone signalling and polarized morphogenesis in yeast.
AB  - Yeast cells respond to mating pheromones by activating a signal transduction
      pathway involving a seven transmembrane receptor/G protein complex linked to a
      mitogen-activated protein kinase module. Regulation of the G protein signal is
      controlled by the receptor and Sst2p; Sst2p may function as a GTPase-activating
      protein for the G protein alpha subunit. The Ste20 kinase acts in the linkage
      between the G protein and the MAP kinase module. Experiments suggest that binding
      of the Rho-like GTPase Cdc42p to Ste20p is not required for the mating response,
      yet is needed for the pseudohyphal growth response which involves many of the
      same kinases.

PMID- 9024635
TI  - Bcl-2 and the ICE family of apoptotic regulators: making a connection.
AB  - Apoptosis, a genetically programmed mechanism of eliminating cells in response to
      a variety of stimuli, provides protection against cancer and viral infections as
      well as maintenance of homeostasis in living organisms. Two classes of molecules,
      the Bcl-2 family of regulators and the ICE family of proteases, have emerged from
      different vertebrate, invertebrate and viral systems that have been used to
      elucidate the pathways leading to apoptosis. However, no connection between these
      two disparate families of apoptotic regulators has been convincingly established.
      In reviewing the recent advances pertaining to the Bcl-2 and ICE-related protein
      families, one can address the question of a functional relationship between the
      two classes of proteins.

PMID- 9024636
TI  - MEKKs, GCKs, MLKs, PAKs, TAKs, and tpls: upstream regulators of the c-Jun amino
      terminal kinases?
AB  - Regulation of the mitogen-activated protein kinase (MAPK) family members - which
      include the extracellular response kinases (ERKs), p38/HOG1, and the c-Jun amino
      terminal kinases (JNKs) - plays a central role in mediating the effects of
      diverse stimuli encompassing cytokines, hormones, growth factors and stresses
      such as osmotic imbalance, heat shock, inhibition of protein synthesis and
      irradiation. A rapidly increasing number of kinases that activate the JNK
      pathways has been described recently, including the MAPK/ERK kinase kinases, p21
      activated kinases, germinal center kinase, mixed lineage kinases, tumor
      progression locus 2, and TGF-beta-activated kinase. Thus, regulation of the JNK
      pathway provides an interesting example of how many different stimuli can
      converge into regulating pathways critical for the determination of cell fate.

PMID- 9024637
TI  - Novel mechanisms of RTK signal generation.
AB  - Recent findings shed new light on the process of receptor tyrosine kinase (RTK)
      activation and signal definition. In extension to the established mechanism of
      ligand-induced homodimeric receptor complex formation, recent findings highlight
      heterodimeric receptor aggregation as a powerful means of signal diversification.
      Promiscuous receptor interactions involve different ligand binding kinetics and
      generate divergent receptor phosphorylation sites that could allow enhanced or
      modified signal generation. Besides activation by a specific ligand, a newly
      defined RTK function involves signal integration of a variety of stimuli,
      including calcium-dependent responses in neuronal cells, activation of G-protein
      coupled receptors or cellular stress such as UV irradiation. On the basis of
      existing evidence for such crossactivation pathways, RTKs must be considered as
      representing critical foci and switch points for multiple environmental and
      internal stimuli.

PMID- 9024638
TI  - DCC's function takes shape in the nervous system.
AB  - Deleted in colorectal cancer (DCC), a candidate tumor-suppressor gene, has
      recently been found to encode a netrin receptor required for axon guidance in
      vitro. Mutations in Caenorhabditis elegans and Drosophila genes encoding DCC
      related proteins affect axon guidance, and these phenotypes resemble those of
      mutations in netrin genes. Netrins and their DCC-related receptors thus play an
      evolutionarily conserved role in midline guidance, and DCC may be required more
      generally for cellular morphogenesis.

PMID- 9024639
TI  - CDKs and cyclins in transition(s).
AB  - Understanding of cyclin-dependent kinase (CDK) regulation in mammalian cells has
      deepened even as the functions ascribed to these enzymes have multiplied. We know
      from crystallographic studies how a prototypic CDK-cyclin complex is activated
      and inactivated; the challenge now is to extend this knowledge to other CDKs
      involved in cell cycle progression. At the same time, as CDKs turn up in some
      unexpected places, interest in CDK regulation has spread beyond the cell cycle
      field.

PMID- 9024641
TI  - Oncogenes and cell proliferation.

PMID- 9024640
TI  - Signal transduction from multiple Ras effectors.
AB  - Ras proteins activate a signaling cascade through direct binding of the
      serine/threonine kinase Raf. They also activate additional signaling pathways
      that are essential for full biological activity. Candidate effectors for these
      pathways include RalGDS and phosphatidyl inositol 3' kinase, as well as several
      other Ras binding proteins the biochemical and biological properties of which are
      poorly understood.

PMID- 9024642
TI  - Oncogenes and cell proliferation.

PMID- 9024643
TI  - Bringing enlightenment to the pursuit of justice.

PMID- 9024644
TI  - Heat rises over UCSD 'misconduct' charge.

PMID- 9024645
TI  - Congress vows to contest 'unacceptable' NIH plans.

PMID- 9024646
TI  - 'Medicinal plants threatened by over-use'.

PMID- 9024647
TI  - Breach of embryo ban leads to resignation.

PMID- 9024648
TI  - Canada calls in police to investigate data loss in HIV blood scandal.

PMID- 9024649
TI  - Canadian Red Cross seeks to reform itself.

PMID- 9024650
TI  - Freedom of choice.

PMID- 9024651
TI  - Schizophrenia. An emerging pathophysiology.

PMID- 9024652
TI  - Protein evolution. How far can sequences diverge?

PMID- 9024653
TI  - New impressions of Src and Hck.

PMID- 9024654
TI  - Common mechanism of infection by lentiviruses.

PMID- 9024655
TI  - Hox genes misled by local environments.

PMID- 9024656
TI  - D2 dopamine receptors and personality traits.

PMID- 9024657
TI  - Three-dimensional structure of the tyrosine kinase c-Src.
AB  - The structure of a large fragment of the c-Src tyrosine kinase, comprising the
      regulatory and kinase domains and the carboxy-terminal tall, has been determined
      at 1.7 A resolution in a closed, inactive state. Interactions among domains,
      stabilized by binding of the phosphorylated tail to the SH2 domain, lock the
      molecule in a conformation that simultaneously disrupts the kinase active site
      and sequesters the binding surfaces of the SH2 and SH3 domains. The structure
      shows how appropriate cellular signals, or transforming mutations in v-Src, could
      break these interactions to produce an open, active kinase.

PMID- 9024658
TI  - Crystal structure of the Src family tyrosine kinase Hck.
AB  - The crystal structure of the haematopoietic cell kinase Hck has been determined
      at 2.6/2.9 A resolution. Inhibition of enzymatic activity is a consequence of
      intramolecular interactions of the enzyme's Src-homology domains SH2 and SH3,
      with concomitant displacement of elements of the catalytic domain. The
      conformation of the active site has similarities with that of inactive cyclin
      dependent protein kinases.

PMID- 9024659
TI  - Evolutionary origin of insect wings from ancestral gills.
AB  - Two hypotheses have been proposed for the origin of insect wings. One holds that
      wings evolved by modification of limb branches that were already present in
      multibranched ancestral appendages and probably functioned as gills. The second
      proposes that wings arose as novel outgrowths of the body wall, not directly
      related to any pre-existing limbs. If wings derive from dorsal structures of
      multibranched appendages, we expect that some of their distinctive features will
      have been built on genetic functions that were already present in the structural
      progenitors of insect wings, and in homologous structures of other arthropod
      limbs. We have isolated crustacean homologues of two genes that have wing
      specific functions in insects, pdm (nubbin) and apterous. Their expression
      patterns support the hypothesis that insect wings evolved from gill-like
      appendages that were already present in the aquatic ancestors of both crustaceans
      and insects.

PMID- 9024660
TI  - Use-dependent increases in glutamate concentration activate presynaptic
      metabotropic glutamate receptors.
AB  - The classical view of fast chemical synaptic transmission is that released
      neurotransmitter acts locally on postsynaptic receptors and is cleared from the
      synaptic cleft within a few milliseconds by diffusion and by specific reuptake
      mechanisms. This rapid clearance restricts the spread of neurotransmitter and,
      combined with the low affinities of many ionotropic receptors, ensures that
      synaptic transmission occurs in a point-to-point fashion. We now show, however,
      that when transmitter release is enhanced at hippocampal mossy fibre synapses,
      the concentration of glutamate increases and its clearance is delayed; this
      allows it to spread away from the synapse and to activate presynaptic inhibitory
      metabotropic glutamate receptors (mGluRs). At normal levels of glutamate release
      during low-frequency activity, these presynaptic receptors are not activated.
      When glutamate concentration is increased by higher-frequency activity or by
      blocking glutamate uptake, however, these receptors become activated, leading to
      a rapid inhibition of transmitter release. This effect may be related to the long
      term depression of mossy fibre synaptic responses that has recently been shown
      after prolonged activation of presynaptic mGluRs (refs 2, 3). The use-dependent
      activation of presynaptic mGluRs that we describe here thus represents a negative
      feedback mechanism for controlling the strength of synaptic transmission.

PMID- 9024661
TI  - Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET.
AB  - Schizophrenia is believed to involve altered activation of dopamine receptors,
      and support for this hypothesis comes from the antipsychotic effect of
      antagonists of the dopamine D2 receptor (D2R). D2R is expressed most highly in
      the striatum, but most of the recent positron emission tomography (PET) studies
      have failed to show any change in D2R densities in the striatum of
      schizophrenics, raising the possibility that other receptors may also be
      involved. In particular, the dopamine D1 receptor (D1R), which is highly
      expressed in the prefrontal cortex, has been implicated in the control of working
      memory, and working memory dysfunction is a prominent feature of schizophrenia.
      We have therefore used PET to examine the distribution of D1R and D2R in brains
      of drug-naive or drug-free schizophrenic patients. Although no differences were
      observed in the striatum relative to control subjects, binding of radioligand to
      D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was
      related to the severity of the negative symptoms (for instance, emotional
      withdrawal) and to poor performance in the Wisconsin Card Sorting Test. We
      propose that dysfunction of D1R signalling in the prefrontal cortex may
      contribute to the negative symptoms and cognitive deficits seen in schizophrenia.

PMID- 9024662
TI  - Bax suppresses tumorigenesis and stimulates apoptosis in vivo.
AB  - The protein p53 is a key tumour-suppressor, as evidenced by its frequent
      inactivation in human cancers. Animal models have indicated that attenuation of
      p53-dependent cell death (apoptosis) can contribute to both the initiation and
      progression of cancer, but the molecular mechanisms are unknown. Although p53
      mediated transcriptional activation is one possible explanation, none of the
      known p53-responsive genes has been shown to function in p53-dependent apoptosis.
      Here we test the role of the death-promoting gene bax in a transgenic mouse brain
      tumour, a model in which p53-mediated apoptosis attenuates tumour growth.
      Inactivation of p53 causes a dramatic acceleration of tumour growth owing to a
      reduction in apoptosis of over ninety per cent. We show that p53-dependent
      expression of bax is induced in slow-growing apoptotic tumours. Moreover, tumour
      growth is accelerated and apoptosis drops by fifty per cent in Bax-deficient
      mice, indicating that it is required for a full p53-mediated response. To our
      knowledge this is the first demonstration that Bax acts as a tumour suppressor,
      and our findings indicate that Bax could be a component of the p53-mediated
      apoptotic response in this system.

PMID- 9024663
TI  - A new class of membrane-bound chemokine with a CX3C motif.
AB  - Chemokines direct the trafficking of white blood cells in immune surveillance,
      playing a key role in inflammatory and infectious diseases such as AIDS. All
      chemokines studied so far are secreted proteins of relative molecular mass
      approximately 7K-15K and fall into three families that are defined by a cysteine
      signature motif: CXC, CC and C (refs 3, 6, 7), where C is a cysteine and X any
      amino-acid residue. We report here the identification and characterization of a
      fourth human chemokine type, derived from non-haemopoietic cells and bearing a
      new CX3C fingerprint. Unlike other chemokine types, the polypeptide chain of the
      human CX3C chemokine is predicted to be part of a 373-amino-acid protein that
      carries the chemokine domain on top of an extended mucin-like stalk. This
      molecule can exist in two forms: either membrane-anchored or as a shed 95K
      glycoprotein. The soluble CX3C chemokine has potent chemoattractant activity for
      T cells and monocytes, and the cell-surface-bound protein, which is induced on
      activated primary endothelial cells, promotes strong adhesion of those
      leukocytes. The structure, biochemical features, tissue distribution and
      chromosomal localization of CX3C chemokine all indicate that it represents a
      unique class of chemokine that may constitute part of the molecular control of
      leukocyte traffic at the endothelium.

PMID- 9024664
TI  - CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia.
AB  - Several members of the chemokine receptor family are used together with CD4 for
      HIV-1 entry into target cells. T cell line-tropic (T-tropic) HIV-1 viruses use
      the chemokine receptor CXCR4 as a co-receptor, whereas macrophage-tropic (M
      tropic) primary viruses use CCR5 (refs 2-6). Individuals with defective CCR5
      alleles exhibit resistance to HIV-1 infection, suggesting that CCR5 has an
      important role in vivo in HIV-1 replication. A subset of primary viruses can use
      CCR3 as well as CCR5 as a co-receptor, but the in vivo contribution of CCR3 to
      HIV-1 infection and pathogenesis is unknown. HIV-1 infects the central nervous
      system (CNS) and causes the dementia associated with AIDS. Here we report that
      the major target cells for HIV-1 infection in the CNS, the microglia, express
      both CCR3 and CCR5. The CCR3 ligand, eotaxin, and an anti-CCR3 antibody inhibited
      HIV-1 infection of microglia, as did MIP-1beta, which is a CCR5 ligand. Our
      results suggest that both CCR3 and CCR5 promote efficient infection of the CNS by
      HIV-1.

PMID- 9024665
TI  - Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement.
AB  - The protein Hck is a member of the Src family of non-receptor tyrosine kinases
      which is preferentially expressed in haematopoietic cells of the myeloid and B
      lymphoid lineages. Src kinases are inhibited by tyrosine-phosphorylation at a
      carboxy-terminal site. The SH2 domains of these enzymes play an essential role in
      this regulation by binding to the tyrosine-phosphorylated tail. The crystal
      structure of the downregulated form of Hck has been determined and reveals that
      the SH2 domain regulates enzymatic activity indirectly; intramolecular
      interactions between the SH3 and catalytic domains appear to stabilize an
      inactive form of the kinase. Here we compare the roles of the SH2 and SH3 domains
      in modulating the activity of Hck in an investigation of the C-terminally
      phosphorylated form of the enzyme. We show that addition of the HIV-1 Nef
      protein, which is a high-affinity ligand for the Hck SH3 domain, to either the
      downregulated or activated form of Hck causes a large increase in Hck catalytic
      activity. The intact SH3-binding motif in Nef is crucial for Hck activation. Our
      results indicate that binding of the Hck SH3 domain by Nef causes a more marked
      activation of the enzyme than does binding of the SH2 domain, suggesting a new
      mechanism for regulation of the activity of tyrosine kinases.

PMID- 9024666
TI  - Interaction between the C. elegans cell-death regulators CED-9 and CED-4.
AB  - Programmed cell death (apoptosis) is an evolutionarily conserved process used by
      multicellular organisms to eliminate cells that are not needed or are potentially
      detrimental to the organism. Members of the Bcl-2 family of mammalian proteins
      are intimately involved in the regulation of apoptosis, but, their precise
      mechanism of action remains unresolved. In Caenorhabditis elegans, the Bcl-2
      homologue CED-9 prevents cell death by antagonizing the death-promoting
      activities of CED-3, a member of the Caspase family of death proteases, and of
      CED-4, a protein with no known mammalian homologue. Here we show that CED-9
      interacts physically with CED-4. Mutations that reduce or eliminate CED-9
      activity also disrupt its ability to bind CED-4, suggesting that this interaction
      is important for CED-9 function. Thus, CED-9 might control C. elegans cell death
      by binding to and regulating CED-4 activity. We propose that mammalian Bcl-2
      family members might control apoptosis in a similar way through interaction and
      regulation of CED-4 homologues or analogues.

PMID- 9024667
TI  - Diverse opportunities for immunologists.

PMID- 9024668
TI  - Inhibition of 3,3',4,4',5-pentachlorobiphenyl-induced chicken embryotoxicity by
      2,2',4,4',5,5'-hexachlorobiphenyl.
AB  - 3,3',4,4',5-Pentachlorobiphenyl (pentaCB) caused a dose-dependent induction of
      chicken embryolethality, malformations, edema, and liver lesions at doses ranging
      from 0.5 to 12.0 microg/kg. In contrast, no embryotoxicity was observed after
      treatment with 10, 25, or 50 mg/kg 2,2',4,4',5,5'-hexaCB. In eggs cotreated with
      2.0 microg/kg, 3,3',4,4',5-pentaCB plus 10, 25, or 50 mg/kg 2,2',4,4',5,5'
      hexaCB, there was significant protection from 3,3',4,4',5-pentaCB-induced embryo
      malformations, edema, and liver lesions, whereas no inhibition of embryolethality
      was observed. These results further extend the response-specific nonadditive
      interactions of binary mixtures of polychlorinated biphenyls (PCBs) and should be
      considered in the development of approaches for hazard assessment of PCB mixtures
      and related compounds.

PMID- 9024669
TI  - Chronic toxicity studies of 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione, a
      potential chemopreventive agent.
AB  - The synthetic compound Oltipraz, 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione,
      is related to the 1,2-dithiolthiones naturally found in cruciferous vegetables,
      the consumption of which has been epidemiologically associated with reduced
      frequency of colorectal cancers. Oltipraz has shown chemopreventive efficacy in
      numerous laboratory epithelial cancer models and is a potential chemopreventive,
      antimutagenic compound that specifically induces Phase II enzymes. Thirteen-week
      and 1-year toxicity studies in rats and dogs were performed to characterize the
      toxicities of the compound at high dosages and to support potential further
      development as a chemopreventive agent in clinical trials. Administration to rats
      by gavage for 13 weeks at dosages of 5 and 50 mg/kg/day and for 52 weeks at
      dosages of 10, 30, and 60 mg/kg/day produced effects on the liver and on clinical
      chemistry and hematology parameters. Absolute and relative liver weight increases
      correlated with diffuse hypertrophy in the mid- and high-dose males and
      centrilobular hypertrophy in the high-dose females. Granularity of hepatocyte
      cytoplasm was also observed. These anatomical findings were associated with dose
      associated slight increases in albumin, total protein, and cholesterol in the
      males and a moderate increase in cholesterol only in the females. In addition,
      slight decreases in erythrocyte count, hemoglobin, and hematocrit and
      reticulocyte elevations occurred. The no effect dose was considered 10 mg/kg/day.
      Administration by capsule to dogs at dosages of 10 and 100 mg/kg/day for 13 weeks
      and of 5, 15, and 60 mg/kg/day for 52 weeks also produced effects on the same
      endpoints noted in the rodent studies. In the 13-week study, precipitate was
      observed in the bile canaliculi, and gonadal atrophy and increased pituitary
      weights occurred in the males. Cholesterol and alkaline phosphatase activity were
      slightly elevated in both studies. Decreased hematology parameters in the 13-week
      study also occurred. The no effect dose was considered to be 5 mg/kg/day.
      Oltipraz is being carefully evaluated in clinical trials as a potential
      antimutagenic compound.

PMID- 9024670
TI  - Oxidative stress in the splenotoxicity of aniline.
AB  - Aniline-induced splenic toxicity is characterized by hemorrhage, capsular
      hyperplasia, fibrosis, and a variety of sarcomas in rats. Early biochemical
      events responsible for the observed effects are not known. To understand the
      mechanism(s) of aniline-induced splenic toxicity, single and multiple (four and
      seven) doses of 1 mmol/kg of aniline hydrochloride(AH) were given in rats. Apart
      from changes in the hematological parameters, these studies demonstrated that AH
      could induce lipid peroxidation and protein oxidation in the spleen, and
      significant increases were observed at four doses. Subsequently, a dose-response
      study of AH was performed. Male SD rats were given four doses each (one dose/day)
      of 0.25, 0.5, 1, and 2 mmol/kg of AH in water by gavage, while controls received
      water only. Animals were euthanized 24 hr following the last dose and tissues
      obtained. Spleen weight increased by 32 and 80% at 1 and 2 mmol/kg doses,
      respectively. Splenic lipid peroxidation showed dose-dependent increases of 24,
      32, and 43% at 0.5, 1, and 2 mmol/kg, respectively. Protein oxidation in the
      spleen, quantitated by carbonyl content per milligram protein, showed 10, 28, and
      27% increases at 0.5, 1, and 2 mmol/kg, respectively. Iron content in the spleen
      also showed dose-dependent increases of 72, 172, and 325% at 0.5, 1, and 2
      mmol/kg, respectively. Dose-related histopathologic expansion of splenic red pulp
      was characterized by increasing vascular congestion (most pronounced at 2
      mmol/kg), increased red pulp cellularity, erythrophagocytosis, and cellular
      fragmentation at 1 and 2 mmol/kg; iron deposition in red pulp also increased
      dramatically with dose. These studies establish that aniline induces lipid
      peroxidation and protein oxidation in the spleen and suggest that oxidative
      stress plays a role in the splenic toxicity of aniline.

PMID- 9024671
TI  - A comparison of the acute neuroactive effects of dichloromethane, 1,3
      dichloropropane, and 1,2-dichlorobenzene on rat flash evoked potentials (FEPs).
AB  - Previous research showed that acute exposure to dichloromethane (DCM) produced a
      selective reduction in peak N30 of flash evoked potentials (FEPs) in rats. In
      contrast, acute exposures to p-xylene or toluene selectively reduced FEP peak
      N160. The present experiments compared the effects of DCM (log P = 1.25;
      oil:water partition coefficient), 1,3-dichloropropane (DCP; log P = 2.00), and
      1,2-dichlorobenzene (DCB; log P = 3.38) on FEPs recorded from adult Long-Evans
      rats. Before administration of test compounds, FEPs were recorded for five daily
      sessions to develop FEP peak N160. Test compounds were dissolved in corn oil and
      administered i.p. at doses based on proportions of their LD50 values. The doses
      were: DCM, 0, 57.5, 115, 230, or 460 mg/kg; DCP, 0, 86, 172, 343, or 686 mg/kg;
      and DCB, 0, 53, 105, 210, or 420 mg/kg. Testing times after dosing varied among
      compounds and were based on pilot studies to measure both the times of peak
      effect and recovery. Each solvent produced significant changes in the latency and
      amplitude of multiple components of the FEP waveforms. However, the predominant
      effect of DCM was to reduce the amplitude of peak N30 (ED50 = 326.3 mg/kg), that
      of DCP was to reduce both peaks N30 (ED50 = 231.0 mg/kg) and N160 (ED50 = 136.8
      mg/kg), and that of DCB was to reduce peak N160 (ED50 = 151.6 mg/kg). There was
      no consistent relationship between log P values and the potency of the compounds
      to alter FEP peaks N30 and N160. The results suggest that organic solvents have
      multiple acute effects on the function of the central nervous system, which are
      not predictable solely by the compound's lipid solubility.

PMID- 9024672
TI  - Characterization of the high sensitivity of rabbits to the effects of TCV-116, an
      angiotensin II receptor antagonist.
AB  - A high incidence of maternal toxicity in rabbits characterized by uremia and
      death was observed when TCV-116, a novel angiotensin II subtype-1 (AT1) receptor
      antagonist, was orally administered to pregnant rabbits at dosage levels of 3
      mg/kg/day or more. The effects of TCV-116 on blood pressure in nonpregnant or
      male rabbits and rats and on blood chemistry, renal circulation, and plasma renin
      activity in nonpregnant or male rabbits were examined to characterize the
      toxicity in rabbits. In a 2-week repeated dose study, most nonpregnant female
      rabbits receiving 3 or 100 mg/kg/day died or were sacrificed in a moribund state,
      indicating that toxicity could be caused independently of pregnancy. When these
      rabbits became moribund, marked hypotension, accompanied by increases in plasma
      concentrations of urea nitrogen, creatinine, and potassium, was observed,
      suggesting uremia. In a single-dose study, blood pressure in rabbits was
      decreased after administration of 10 or 100 mg/kg of TCV-116, and the hypotension
      was more marked and sustained than that in rats, as was the case with 30 mg/kg of
      enalapril. The sustained pharmacological effect in rabbits was also confirmed
      with regard to decreases in effective renal plasma flow and the glomerular
      filtration rate and increased plasma renin activity. Species differences in the
      hypotensive effect and mortality could not be explained by toxicokinetic data for
      the active metabolite of TCV-116 in various species, which supported a
      possibility that the differences in toxicity may be related to the species
      difference in sensitivity to the pharmacological effect of TCV-116. We conclude
      that the specific maternal toxicity of TCV-116 in rabbits may be mainly due to
      the higher sensitivity of rabbits to the pharmacological effects and is caused by
      marked and sustained hypotension resulting in the decrease in glomerular
      filtration rate, uremia, and death.

PMID- 9024673
TI  - Eight-week toxicity study of 60 Hz magnetic fields in F344 rats and B6C3F1 mice.
AB  - Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice (10
      animals per sex per species per group) to transient-free, linearly polarized 60
      Hz magnetic fields for 8 weeks. Targeted magnetic fields strengths used were 0
      gauss (G; sham control fields did not exceed 0.001 G), 0.02 G, 2 G, and 10 G.
      Exposure was whole-body and continuous for 18.5 hr per day, 7 days per week. An
      additional group of rats and mice was exposed intermittently (1 hr on/1 hr off)
      to 10 G fields for the same period of time. Endpoints evaluated included
      morbidity, mortality, gross pathology, histopathology, body/organ weights,
      clinical chemistry (rats only), and hematology (rats only). All mice and all male
      rats survived until the end of the study. One female rat (2-G exposure group)
      died during Week 7 of the study; the death was not attributed to magnetic field
      exposure. In both studies, the mean body weight gains of exposed animals were
      similar to those of the respective controls. There were no gross, histological,
      hematological, or biochemical lesions attributed to magnetic field exposure.
      Statistically significant increases in liver weight and liver to body weight
      ratio occurred in female rats of all exposure groups but only at the termination.
      These data suggest that, for the variables evaluated in these studies, an 8-week
      exposure to linear-polarized, transient-free 60 Hz magnetic fields at field
      intensities of up to 10 G is not associated with significant toxicity in F344/N
      rats and B6C3F1 mice. Furthermore, there was no toxicity observed in animals
      receiving intermittent (1 hr on/1 hr off) exposures to 10-G fields. A 2-year
      study in F344/N rats and B6C3F1 mice is nearing completion of the in-life phase
      without overt toxicity in any exposed group. It is premature, however, to make
      any prediction concerning the possible influence of exposure to 60 Hz magnetic
      fields on cancer rates.

PMID- 9024674
TI  - Acute and subchronic inhalation studies on trifluoroiodomethane vapor in Fischer
      344 rats.
AB  - Trifluoroiodomethane (CF3I) is being considered as a replacement compound for
      halon fire suppressants. Its structure is similar to that of Halon 1301 (CF3Br),
      but it has very low ozone depletion potential compared to CF3Br. As part of the
      process of developing environmental and health effects criteria, acute, 2-week,
      and 13-week nose-only inhalation toxicity studies were conducted in Fischer 344
      rats. In the acute study, three groups of 30 male rats each were exposed to 0
      (control), 0.5, or 1.0% (v/v) CF3I for 4 hr and euthanized immediately following
      exposure, 3 days postexposure, or 14 days postexposure. There were no deaths and
      no clinical signs of toxicity throughout the study. Histopathologic examination
      of select tissues showed no lesions of pathologic significance. In the 2-week
      study, four groups of 5 male rats each were exposed for 2 hr/day, 5 days/week to
      0, 3, 6, or 12% CF3I. No deaths were observed, though lethargy and slight
      incoordination were noted in rats of the 6 and 12% groups at the conclusion of
      each daily exposure. Mean body weight gains were depressed in rats of the 6 and
      12% groups. Serum thyroglobulin and reverse T3 (rT3) values were increased at all
      exposure levels. At necropsy, no gross lesions or differences in absolute or
      relative organ weights were noted. Histopathologic examination of the thyroid and
      parathyroid glands indicated no morphological abnormalities in the CF3I-exposed
      rats. In the 13-week study, four groups of 15 male and 15 female rats were
      exposed to 0, 2, 4, or 8% CF3I 2 hr/day, 5 days/week for 13 weeks. Rats exposed
      to 4 or 8% CF3I had lower mean body weights than the controls. Deaths observed in
      the 2 and 8% groups were attributed to accidents resulting from the restraint
      system employed. Hematologic alterations were minimal and considered
      insignificant. Increases in the frequency of micronucleated bone marrow
      polychromatic erythrocytes were observed in rats of all three CF3I groups. Serum
      chemistry alterations observed in rats of all CF3I exposure groups included
      decreases in T3 and increases in thyroglobulin, rT3, T4, and TSH. Relative organ
      weight increases (8% CF3I group) occurred in the brain, liver, and thyroid
      glands; decreases were observed in the thymus and testes. A decrease in relative
      thymus weights and an increase in relative thyroid weights were observed also in
      rats of the 2 and 4% groups. Histopathological findings included a mild
      inflammation in the nasal turbinates of rats exposed to 4 or 8% CF3I, mild
      atrophy and degeneration of the testes (4 and 8% CF3I groups), and a mild
      increase in thyroid follicular colloid content in rats of all CF3I exposure
      groups. Though NOAELs were observed for select target organs (e.g., nasal
      turbinates, testes), NOAELs were not apparent in all target organs examined
      (e.g., thyroid glands, bone marrow).

PMID- 9024675
TI  - Effect of dexamethasone on ciprofibrate-induced cell proliferation and peroxisome
      proliferation.
AB  - Peroxisome proliferators cause liver cell proliferation in addition to other
      pleiotropic effects such as peroxisome proliferation and induction of certain
      peroxisomal and cytosolic enzymes in liver. Since dexamethasone has been shown to
      inhibit mitogen-induced liver cell hyperplasia, we examined whether dexamethasone
      inhibits only cell proliferation without affecting peroxisome proliferation
      induced by peroxisome proliferators such as ciprofibrate. Livers of rats fed a
      diet containing ciprofibrate (0.025%) with or without added dexamethasone (0.5 mg
      or 1 mg/kg diet) for 1 week were evaluated for hepatocyte proliferation and
      peroxisome proliferation. Dexamethasone administration resulted in abrogation of
      ciprofibrate-induced cell proliferation as shown by bromodeoxyuridine (BrdU)
      labeling and mitoses counts. The hepatocyte proliferative index measured after
      administration of a single dose of BrdU was 18.3 +/- 1.1 and 2.3 +/- 0.7% (p <
      0.01) in ciprofibrate and ciprofibrate + dexamethasone treated rats,
      respectively. With multiple injections of BrdU (daily injections for 7 days) the
      proliferative index was 225 +/- 10 and 183 +/- 2% (p < 0.02), respectively, in
      these two groups. Interestingly, whereas the levels of peroxisome proliferator
      induced Mr 80,000 polypeptide and catalase and peroxisomal bifunctional enzyme,
      and the corresponding mRNAs and peroxisome volume density were unaffected. These
      results show that dexamethasone selectively inhibits only cell proliferation
      without inhibiting the peroxisome proliferation caused by ciprofibrate. This
      model should be useful for examining the role of cell proliferation versus
      oxidative stress in peroxisome proliferator-induced hepatocarcinogenesis.

PMID- 9024676
TI  - A murine model of genetic susceptibility to lead bioaccumulation.
AB  - Previous reports have shown that blood lead levels in humans are associated with
      a polymorphic form of delta-aminolevulinate dehydratase (ALAD), an enzyme of heme
      biosynthesis that binds and is inhibited by lead. We hypothesized that ALAD
      levels may influence the distribution and accumulation of lead in the blood and
      target organs. To assess this, we studied strains of mice that differ in the
      numbers of copies of the ALAD gene. Our findings showed that mice with a
      duplication of the ALAD gene (DBA) accumulated twice the amount of lead in their
      blood and had higher lead levels in kidney and liver than mice with a single copy
      of the gene (C57) exposed to the same oral doses of lead during adulthood. Hybrid
      animals showed intermediate blood lead levels. Levels of blood zinc
      protoporphyrin (ZPP) increased with lead exposure in C57 animals while they were
      not affected in DBA mice, suggesting protection from production of this abnormal
      enzyme in mice with a duplication of the gene. Except for these protective
      effects in the formation of ZPP in DBA animals, duplication of the ALAD gene was
      found to increase lead accumulation. We conclude that although these mouse
      strains do not precisely replicate the polymorphism observed in humans, they may
      be used as a model to study genetic influences in lead bioaccumulation.
      Understanding genetic factors that affect susceptibility to lead-induced
      intoxication could have important implications for public health and intervention
      initiatives. These mouse strains may represent a useful model for future study of
      the role of ALAD in lead intoxication.

PMID- 9024677
TI  - Uptake of acetaldehyde vapor and aldehyde dehydrogenase levels in the upper
      respiratory tracts of the mouse, rat, hamster, and guinea pig.
AB  - Acetaldehyde is a ubiquitous indoor and outdoor air pollutant. This vapor is a
      respiratory tract irritant and a rodent inhalation carcinogen. The current study
      was aimed at examining the upper respiratory tract (URT) deposition efficiency
      for this vapor at inspired concentrations of 1, 10, 100, or 1000 ppm in four
      rodent species: B6C3F1 mouse, Sprague-Dawley rat, Syrian hamster, and Hartley
      guinea pig. For measurement of vapor uptake, the URT was isolated in urethane
      anesthetized animals via insertion of a polyethylene cannula in the trachea such
      that its tip lay at the larynx. Uptake was measured under constant velocity
      unidirectional inspiratory flow at flow rates of approximately 50, 100, 200, and
      300% of the predicted minute ventilation of each species and also under pseudo
      cyclic flow (sinusoidal flow at 100% of the predicted minute ventilation with a
      constant 7 ml/min bleed for analysis). In addition, aldehyde dehydrogenase
      (AldDH) activities were measured in whole nasal tissue homogenates from each
      species for comparative purposes. In all species a high-affinity (Km < 0.2 mM),
      low-capacity AldDH isozyme was observed. In the mouse, hamster, and rat, a low
      affinity (Km > 10 mM), high-capacity isozyme was observed; this isozyme was not
      observed in nasal tissue homogenates of the guinea pig. In all species, URT
      deposition efficiency was strongly dependent on the inspired concentration, with
      uptake being two- to three-fold more efficient at inspired concentrations of 1 or
      10 ppm than at 1000 ppm. For example, at flows approximating the twice-minute
      ventilation rate URT uptake efficiency averaged 43, 49, 28, and 43% in the mouse,
      hamster, rat, and guinea pig, respectively, at an inspired concentration of 10
      ppm, compared to 27, 14, 16, and 6% at an inspired concentration of 1000 ppm.
      Species differences were observed in uptake efficiency. At an inspired
      concentration of 1000 ppm a two-factor analysis of variance followed by a Newman
      Keuls test revealed that uptake was significantly higher in the mouse, rat, and
      hamster than in the guinea pig. In contrast, at 10 ppm uptake was significantly
      lower in the rat than in any other species. Thus, the rank order of these species
      on the basis of ability to scrub acetaldehyde from the airstream differed at high
      compared to low inspired concentrations. The documentation of greatly differing
      deposition efficiencies as well as differing relative dosimetric relationships
      among species at high compared to low exposure concentrations highlights the
      potential complexities of quantitative extrapolation of high-concentration rodent
      inhalation toxicity data.

PMID- 9024678
TI  - Subchronic neurotoxicity screening studies with six organophosphate insecticides:
      an assessment of behavior and morphology relative to cholinesterase inhibition.
AB  - Sulprofos, disulfoton, azinphos-methyl, methamidophos, trichlorfon, and
      tebupirimphos were screened for neurotoxic potential, in accordance with U.S. EPA
      (FIFRA) requirements. Each organophosphate was administered through the diet for
      13 weeks to separate groups of Fischer 344 rats at four dose levels, including a
      vehicle control. For each study, 12 rats/sex/dietary level were tested using a
      functional observational battery (FOB), automated measures of activity (figure-8
      maze), and detailed clinical observations, with half of the animals perfused at
      term for microscopic examination of neural and muscle tissues. Separate groups of
      satellite animals (6/sex/dietary level) were used to measure the effect of each
      treatment on plasma, erythrocyte (RBC), and brain cholinesterase (ChE) activity.
      The results show that measures of ChE activity were consistently the most
      sensitive indices of exposure and assisted in the interpretation of findings. All
      treatment-related neurobehavioral findings were ascribed to cholinergic toxicity,
      occurring only at dietary levels that produced more than 20% inhibition of
      plasma, RBC, and brain ChE activity. Neurobehavioral tests provided no evidence
      of additional cumulative toxicity after 8 weeks of treatment. The FOB and motor
      activity findings did not alter the conclusions and generally did not reduce the
      neurobehavioral no-observed-effect level (NOEL) for any of the six compounds,
      relative to the results from detailed clinical observations as conducted in these
      studies. The one exception occurred with tebupirimphos, where the NOEL for motor
      activity was one dose level lower than the NOEL for the FOB and clinical
      observations. These results support the value of detailed clinical observations
      to screen for the neurotoxic potential of organophosphates and a general standard
      of more than 20% inhibition of brain ChE activity for cholinergic neurotoxicity.

PMID- 9024679
TI  - Promotion of altered hepatic foci by 2,3',4,4',5-pentachlorobiphenyl in Sprague
      Dawley female rats.
AB  - The tumor promotion potential of 2,3',4,4',5-pentachlorobiphenyl (PCB-118) was
      studied in a two-stage initiation/promotion bioassay in female Sprague-Dawley
      rats. The animals were initiated by intraperitoneal administration of N
      nitrosodiethylamine after partial hepatectomy. After 5 weeks of recovery, the
      promotion period commenced by once-weekly subcutaneous administrations of PCB-118
      at six dose levels (10, 40, 160, 640, 2500, and 10,000 microg/kg body
      weight/week) for 20 weeks. In addition, three of these dose levels (40, 640, and
      10,000 microg/kg body weight/week) were administered for 52 weeks. Evaluation of
      hepatic foci positive for glutathione S-transferase P demonstrated that the mono
      ortho chlorine substituted congener PCB-118 significantly increased the number of
      foci/cm3 of liver in the two highest dose groups after 20 weeks, but did not
      significantly increase the percentage of the liver occupied by foci. After 52
      weeks of treatment, both the percentage and the number of foci/cm3 were
      significantly increased in the highest dose group. A toxic equivalency factor
      based on foci development during 20 weeks of treatment would be less than
      0.00002. Altered relative liver and thymus weights were observed after treatment
      with both substances as well as an induction of methyl cholanthrene- and
      phenobarbital-inducible isoenzymes of cytochrome P450 monooxygenase. These
      results show that PCB-118 has a potency to enhance foci growth in rat liver,
      although the potency is low compared to that of structurally related compounds.

PMID- 9024680
TI  - Determination of N7- and O6-methylguanine in rat liver DNA after oral exposure to
      hydrazine by use of immunochemical and electrochemical detection methods.
AB  - Hydrazine belongs to a group of compounds for which there is evidence that the in
      vivo genotoxic effects become manifest only upon exposure to toxic dose levels.
      The present study was performed to investigate whether this phenomenon is also
      reflected in the pattern of DNA methylation. The induction of N7- and O6
      methylguanine (MeGua) was studied in liver DNA of rats, 16 hr after treatment
      with various doses of hydrazine. After DNA isolation, the presence of N7-MeGua in
      DNA was assessed with an immunochemical method and with a physicochemical
      technique (HPLC with electrochemical detection). Application of these two methods
      resulted in almost identical patterns of dose-dependent induction of guanine N7
      methylation in rats dosed orally with 0.1 to 10 mg hydrazine per kilogram of body
      weight, increasing from 1.1-1.3 to 39-45 N7-MeGua per 10(6) nucleotides. At lower
      dosages a constant adduct level was observed, equivalent to that in untreated
      rats (background level). The O6-MeGua level was analyzed by a combination of HPLC
      separation and competitive radioimmunoassay. A background level was observed for
      untreated rats and no increase was visible up to the 0.2 mg/kg dose group. After
      hydrazine doses from 0.2 to 10 mg/kg, O6-MeGua increased from 0.29 to 134 per
      10(9) nucleotides. These data show that even at dosages below the maximum
      tolerated dose (0.6 mg/kg/day), for which carcinogenic effects have not been
      described, DNA adducts are formed. A comparison is made of the data obtained in
      this study with models that describe the mechanism of hydrazine-induced DNA
      methylation.

PMID- 9024681
TI  - Dichloromethane potentiation of carbon tetrachloride hepatotoxicity in rats.
AB  - Concomitant treatment of rats with a nonhepatotoxic dose of dichloromethane (6
      mmol/kg, i.p.) significantly potentiated the hepatotoxicity of carbon
      tetrachloride (2 mmol/kg, i.p.). Toxicity was determined by increases in serum
      sorbitol dehydrogenase and alanine aminotransferase activities measured 24 hr
      following the treatments. Dichloromethane did not affect the lipid peroxidation
      induced by carbon tetrachloride as determined by conjugated diene formation in
      hepatic microsomal lipids. The covalent binding of [14C]Cl4 metabolites to
      microsomal lipids was increased significantly by dichloromethane. The results
      suggest that dichloromethane potentiates carbon tetrachloride hepatotoxicity by
      increasing covalent binding of its metabolites to hepatic microsomal lipids.

PMID- 9024682
TI  - A centromere DNA-binding protein from fission yeast affects chromosome
      segregation and has homology to human CENP-B.
AB  - Genetic and biochemical strategies have been used to identify Schizosaccharomyces
      pombe proteins with roles in centromere function. One protein, identified by both
      approaches, shows significant homology to the human centromere DNA-binding
      protein, CENP-B, and is identical to Abp1p (autonomously replicating sequence
      binding protein 1) (Murakami, Y., J.A. Huberman, and J. Hurwitz. 1996. Proc.
      Natl. Acad. Sci. USA. 93:502-507). Abp1p binds in vitro specifically to at least
      three sites in centromeric central core DNA of S. pombe chromosome II (cc2).
      Overexpression of abp1 affects mitotic chromosome stability in S. pombe. Although
      inactivation of the abp1 gene is not lethal, the abp1 null strain displays marked
      mitotic chromosome instability and a pronounced meiotic defect. The
      identification of a CENP-B-related centromere DNA-binding protein in S. pombe
      strongly supports the hypothesis that fission yeast centromeres are structurally
      and functionally related to the centromeres of higher eukaryotes.

PMID- 9024683
TI  - Assembly of CENP-A into centromeric chromatin requires a cooperative array of
      nucleosomal DNA contact sites.
AB  - We investigated the requirements for targeting the centromeric histone H3
      homologue CENP-A for assembly at centromeres in human cells by transfection of
      epitope-tagged CENP-A derivatives into HeLa cells. Centromeric targeting is
      driven solely by the conserved histone fold domain of CENP-A. Using the crystal
      structure of histone H3 as a guide, a series of CENP-A/histone H3 chimeras was
      constructed to test the role of discrete structural elements of the histone fold
      domain. Three elements were identified that are necessary for efficient targeting
      to centromeres. Two correspond to contact sites between histone H3 and
      nucleosomal DNA. The third maps to a homotypic H3-H3 interaction site important
      for assembly of the (H3/H4)2 heterotetramer. Immunoprecipitation confirms that
      CENP-A self-associates in vivo. In addition, targeting requires that CENP-A
      expression is uncoupled from histone H3 synthesis during S phase. CENP-A mRNA
      accumulates later in the cell cycle than histone H3, peaking in G2. Isolation of
      the gene for human CENP-A revealed a regulatory motif in the promoter region that
      directs the late S/G2 expression of other cell cycle-dependent transcripts such
      as cdc2, cdc25C, and cyclin A. Our data suggest a mechanism for molecular
      recognition of centromeric DNA at the nucleosomal level mediated by a cooperative
      series of differentiated CENP-A-DNA contact sites arrayed across the surface of a
      CENP-A nucleosome and a distinctive assembly pathway occurring late in the cell
      cycle.

PMID- 9024684
TI  - Identification of protein p270/Tpr as a constitutive component of the nuclear
      pore complex-attached intranuclear filaments.
AB  - Using a monoclonal antibody, mAb 203-37, we have identified a polypeptide of M(r)
      approximately 270 kD (p270) as a general constituent of the intranuclear
      filaments attached to the nucleoplasmic annulus of the nuclear pore complex (NPC)
      in diverse kinds of vertebrate cells. Using cDNA cloning and immunobiochemistry,
      we show that human protein p270 has a predicted molecular mass of 267 kD and is
      essentially identical to the coiled-coil dominated protein Tpr reported by others
      to be located on the outer, i.e., cytoplasmic surface of NPCs (Byrd, D.A., D.J.
      Sweet, N. Pante, K.N. Konstantinov, T. Guan, A.C.S. Saphire, P.J. Mitchell, C.S.
      Cooper, U. Aebi, and L. Gerace. 1994. J. Cell Biol. 127: 1515-1526). To clarify
      this controversial localization, we have performed immunoelectron microscopy in
      diverse kinds of mammalian and amphibian cells with a series of antibodies raised
      against different epitopes of human and Xenopus laevis p270/Tpr. In these
      experiments, the protein has been consistently and exclusively detected in the
      NPC-attached intranuclear filaments, and p270/Tpr-containing filament bundles
      have been traced into the nuclear interior for up to 350 nm. No reaction has been
      noted at the cytoplasmic side of NPCs with any of the p270/Tpr antibodies,
      whereas control antibodies such as those against protein RanBP2/Nup358
      specifically decorate the cytoplasmic annulus of NPCs. Pore complexes of
      cytoplasmic annulate lamellae in various mammalian and amphibian cells are also
      devoid of immunodetectable protein p270/Tpr. We conclude that this coiled-coil
      protein is a general and ubiquitous component of the intranuclear NPC-attached
      filaments and discuss its possible functions.

PMID- 9024685
TI  - Interphase nuclei of many mammalian cell types contain deep, dynamic, tubular
      membrane-bound invaginations of the nuclear envelope.
AB  - The nuclear envelope consists of a double-membraned extension of the rough
      endoplasmic reticulum. In this report we describe long, dynamic tubular channels,
      derived from the nuclear envelope, that extend deep into the nucleoplasm. These
      channels show cell-type specific morphologies ranging from single short stubs to
      multiple, complex, branched structures. Some channels transect the nucleus
      entirely, opening at two separate points on the nuclear surface, while others
      terminate at or close to nucleoli. These channels are distinct from other
      topological features of the nuclear envelope, such as lobes or folds. The channel
      wall consists of two membranes continuous with the nuclear envelope, studded with
      features indistinguishable from nuclear pore complexes, and decorated on the
      nucleoplasmic surface with lamins. The enclosed core is continuous with the
      cytoplasm, and the lumenal space between the membranes contains soluble ER
      resident proteins (protein disulphide isomerase and glucose-6-phosphatase).
      Nuclear channels are also found in live cells labeled with the lipophilic dye
      DiOC6. Time-lapse imaging of DiOC6-labeled cells shows that the channels undergo
      changes in morphology and spatial distribution within the interphase nucleus on a
      timescale of minutes. The presence of a cytoplasmic core and nuclear pore
      complexes in the channel walls suggests a possible role for these structures in
      nucleo-cytoplasmic transport. The clear association of a subset of these
      structures with nucleoli would also be consistent with such a transport role.

PMID- 9024686
TI  - Mdm12p, a component required for mitochondrial inheritance that is conserved
      between budding and fission yeast.
AB  - Saccharomyces cerevisiae cells lacking the MDM12 gene product display temperature
      sensitive growth and possess abnormally large, round mitochondria that are
      defective for inheritance by daughter buds. Analysis of the wild-type MDM12 gene
      revealed its product to be a 31-kD polypeptide that is homologous to a protein of
      the fission yeast Schizosaccharomyces pombe. When expressed in S. cerevisiae, the
      S. pombe Mdm12p homolog conferred a dominant-negative phenotype of giant
      mitochondria and aberrant mitochondrial distribution, suggesting partial
      functional conservation of Mdm12p activity between budding and fission yeast. The
      S. cerevisiae Mdm12p was localized by indirect immunofluorescence microscopy and
      by subcellular fractionation and immunodetection to the mitochondrial outer
      membrane and displayed biochemical properties of an integral membrane protein.
      Mdm12p is the third mitochondrial outer membrane protein required for normal
      mitochondrial morphology and distribution to be identified in S. cerevisiae and
      the first such mitochondrial component that is conserved between two different
      species.

PMID- 9024687
TI  - Interactions between newly synthesized glycoproteins, calnexin and a network of
      resident chaperones in the endoplasmic reticulum.
AB  - Calnexin is a membrane-bound lectin and a molecular chaperone that binds newly
      synthesized glycoproteins in the endoplasmic reticulum (ER). To analyze the
      oligomeric properties of calnexin and calnexin-substrate complexes, sucrose
      velocity gradient centrifugation and chemical cross-linking were used. After
      CHAPS solubilization of Chinese Hamster Ovary cells, the unoccupied calnexin
      behaved as a monomer sedimenting at 3.5 S20,W. For calnexin-substrate complexes
      the S-values ranged between 3.5-8 S20,W, the size increasing with the molecular
      weight of the substrate. Influenza hemagglutinin, a well-characterized substrate
      associated with calnexin in complexes that sedimented at 5-5.5 S20,W. The
      majority of stable complexes extracted from cells, appeared to contain a single
      calnexin and a single substrate molecule, with about one third of the calnexin in
      the cell being unoccupied or present in weak associations. However, when chemical
      cross-linking was performed in intact cells, the calnexin-substrate complexes and
      calnexin itself was found to be part of a much larger heterogeneous protein
      network that included other ER proteins. Pulse-chase analysis of influenza
      infected cells combined with chemical cross-linking showed that HA was part of
      large, heterogeneous, cross-linked entities during the early phases of folding,
      but no longer after homotrimer assembly. The network of weakly associated
      resident ER chaperones which included BiP, GRP94, calreticulin, calnexin, and
      other proteins, may serve as a matrix that binds early folding and assembly
      intermediates and restricts their exit from the ER.

PMID- 9024688
TI  - A multistep, ATP-dependent pathway for assembly of human immunodeficiency virus
      capsids in a cell-free system.
AB  - To understand the mechanism by which human immunodeficiency virus type 1 (HIV)
      capsids are formed, we have reconstituted the assembly of immature HIV capsids de
      novo in a cell-free system. Capsid authenticity is established by multiple
      biochemical and morphologic criteria. Known features of the assembly process are
      closely reproduced, indicating the fidelity of the cell-free reaction. Assembly
      is separated into co- and posttranslational phases, and three independent
      posttranslational requirements are demonstrated: (a) ATP, (b) a detergent
      sensitive host factor, and (c) a detergent-insensitive host subcellular fraction
      that can be depleted and reconstituted. Assembly appears to proceed by way of
      multiple intermediates whose conversion to completed capsids can be blocked by
      either ATP depletion or treatment with nondenaturing detergent. Specific subsets
      of these intermediates accumulate upon expression of various assembly-defective
      Gag mutants in the cell-free system, suggesting that each mutant is blocked at a
      particular step in assembly. Furthermore, the accumulation of complexes of
      similar sizes in cells expressing the corresponding mutants suggests that
      comparable intermediates may exist in vivo. From these data, we propose a multi
      step pathway for the biogenesis of HIV capsids, in which the assembly process can
      be disrupted at a number of discrete points.

PMID- 9024689
TI  - An alpha-helical signal in the cytosolic domain of the interleukin 2 receptor
      beta chain mediates sorting towards degradation after endocytosis.
AB  - High-affinity IL2 receptors consist of three components, the alpha, beta, and
      gamma chains that are associated in a noncovalent manner. Both the beta and gamma
      chains belong to the cytokine receptor superfamily. Interleukin 2 (IL2) binds to
      high-affinity receptors on the cell surface and IL2-receptor complexes are
      internalized. After endocytosis, the components of this multimolecular receptor
      have different intracellular fates: one of the chains, alpha, recycles to the
      plasma membrane, while the others, beta and gamma, are routed towards late
      endocytic compartments and are degraded. We show here that the cytosolic domain
      of the beta chain contains a 10-amino acid sequence which codes for a sorting
      signal. When transferred to a normally recycling receptor, this sequence diverts
      it from recycling. The structure of a 17-amino acid segment of the beta chain
      including this sequence has been studied by nuclear magnetic resonance and
      circular dichroism spectroscopy, which revealed that the 10 amino acids
      corresponding to the sorting signal form an amphipathic alpha helix. This work
      thus describes a novel, highly structured signal, which is sufficient for sorting
      towards degradation compartments after endocytosis.

PMID- 9024690
TI  - Microdomain Ca2+ activation during exocytosis in Paramecium cells. Superposition
      of local subplasmalemmal calcium store activation by local Ca2+ influx.
AB  - In Paramecium tetraurelia, polyamine-triggered exocytosis is accompanied by the
      activation of Ca2+-activated currents across the cell membrane (Erxleben. C., and
      H. Plattner. 1994. J. Cell Biol. 127:935-945). We now show by voltage clamp and
      extracellular recordings that the product of current x time (As) closely
      parallels the number of exocytotic events. We suggest that Ca2+ mobilization from
      subplasmalemmal storage compartments, covering almost the entire cell surface, is
      a key event. In fact, after local stimulation, Ca2+ imaging with high time
      resolution reveals rapid, transient, local signals even when extracellular Ca2+
      is quenched to or below resting intracellular Ca2+ concentration ([Ca2+]e, < or =
      [Ca2+]i). Under these conditions, quenched-flow/freeze-fracture analysis shows
      that membrane fusion is only partially inhibited. Increasing [Ca2+], alone, i.e.,
      without secretagogue, causes rapid, strong cortical increase of [Ca2+]i but no
      exocytosis. In various cells, the ratio of maximal vs. minimal currents
      registered during maximal stimulation or single exocytotic events, respectively,
      correlate nicely with the number of Ca stores available. Since no quantal current
      steps could be observed, this is again compatible with the combined occurrence of
      Ca2+ mobilization from stores (providing close to threshold Ca2+ levels) and Ca2+
      influx from the medium (which per se does not cause exocytosis). This implies
      that only the combination of Ca2+ flushes, primarily from internal and
      secondarily from external sources, can produce a signal triggering rapid, local
      exocytotic responses, as requested for Paramecium defense.

PMID- 9024691
TI  - A cytosolic serine endopeptidase from Trypanosoma cruzi is required for the
      generation of Ca2+ signaling in mammalian cells.
AB  - An early event in the Trypanosoma cruzi cell invasion process, the recruitment of
      host lysosomes, led us to investigate the involvement of signal transduction.
      Infective trypomastigotes were found to contain a soluble Ca2+-signaling activity
      for mammalian cells that is sensitive to protease inhibitors. Inhibitor and
      substrate utilization profiles were used to purify a candidate peptidase for
      involvement in this process, from which we isolated a full-length cDNA clone. The
      sequence revealed a novel enzyme, denominated T. cruzi oligopeptidase B, which is
      homologous to members of the prolyl oligopeptidase family of serine hydrolases,
      known to participate in the maturation of biologically active peptides. The T.
      cruzi oligopeptidase B was expressed as a fully active product in Escherichia
      coli, and antibodies to the recombinant enzyme inhibited both peptidase activity
      and Ca2+ signaling induced in normal rat kidney cells by trypomastigote extracts.
      Our data suggest that the T. cruzi oligopeptidase B participates in processing
      events in the cytoplasm of the parasites, generating a factor with Ca2+-signaling
      activity for mammalian cells.

PMID- 9024692
TI  - Small, membrane-bound, alternatively spliced forms of ankyrin 1 associated with
      the sarcoplasmic reticulum of mammalian skeletal muscle.
AB  - We have recently found that the erythroid ankyrin gene, Ank1, expresses isoforms
      in mouse skeletal muscle, several of which share COOH-terminal sequence with
      previously known Ank1 isoforms but have a novel, highly hydrophobic 72-amino acid
      segment at their NH2 termini. Here, through the use of domain-specific peptide
      antibodies, we report the presence of the small ankyrins in rat and rabbit
      skeletal muscle and demonstrate their selective association with the sarcoplasmic
      reticulum. In frozen sections of rat skeletal muscle, antibodies to the spectrin
      binding domain (anti-p65) react only with a 210-kD Ank1 and label the sarcolemma
      and nuclei, while antibodies to the COOH terminus of the small ankyrin (anti-p6)
      react with peptides of 20 to 26 kD on immunoblots and decorate the myoplasm in a
      reticular pattern. Mice homozygous for the normoblastosis mutation (gene symbol
      nb) are deficient in the 210-kD ankyrin but contain normal levels of the small
      ankyrins in the myoplasm. In nb/nb skeletal muscle, anti-p65 label is absent from
      the sarcolemma, whereas anti-p6 label shows the same distribution as in control
      skeletal muscle. In normal skeletal muscle of the rat, anti-p6 decorates Z lines,
      as defined by antidesmin distribution, and is also present at M lines where it
      surrounds the thick myosin filaments. Immunoblots of the proteins isolated with
      rabbit sarcoplasmic reticulum indicate that the small ankyrins are highly
      enriched in this fraction. When expressed in transfected HEK 293 cells, the small
      ankyrins are distributed in a reticular pattern resembling the ER if the NH2
      terminal hydrophobic domain is present, but they are uniformly distributed in the
      cytosol if this domain is absent. These results suggest that the small ankyrins
      are integral membrane proteins of the sarcoplasmic reticulum. We propose that,
      unlike the 210-kD form of Ank1, previously localized to the sarcolemma and
      believed to be a part of the supporting cytoskeleton, the small Ank1 isoforms may
      stabilize the sarcoplasmic reticulum by linking it to the contractile apparatus.

PMID- 9024693
TI  - Myosin I overexpression impairs cell migration.
AB  - Dictyostelium myoB, a member of the myosin I family of motor proteins, is
      important for controlling the formation and retraction of membrane projections by
      the cell's actin cortex (Novak, K.D., M.D. Peterson, M.C. Reedy, and M.A. Titus.
      1995. J. Cell Biol. 131:1205-1221). Mutants that express a three- to sevenfold
      excess of myoB (myoB+ cells) were generated to further analyze the role of myosin
      I in these processes. The myoB+ cells move with an instantaneous velocity that is
      35% of the wild-type rate and exhibit a 6-8-h delay in initiation of aggregation
      when placed under starvation conditions. The myoB+ cells complete the
      developmental cycle after an extended period of time, but they form fewer
      fruiting bodies that appear to be small and abnormal. The myoB+ cells are also
      deficient in their ability both to form distinct F-actin filled projections such
      as crowns and to become elongate and polarized. This defect can be attributed to
      the presence of at least threefold more myoB at the cortex of the myoB+ cells. In
      contrast, threefold overexpression of a truncated myoB that lacks the src
      homology 3 (SH3) domain (myoB/SH3- cells) or myoB in which the consensus heavy
      chain phosphorylation site was mutated to an alanine (S332A-myoB) does not
      disturb normal cellular function. However, there is an increased concentration of
      myoB in the cortex of the myoB/SH3- and S332A-myoB cells comparable to that found
      in the myoB+ cells. These results suggest that excess full-length cortical myoB
      prevents the formation of the actin-filled extensions required for locomotion by
      increasing the tension of the F-actin cytoskeleton and/or retracting projections
      before they can fully extend. They also demonstrate a role for the
      phosphorylation site and SH3 domain in mediating the in vivo activity of myosin
      I.

PMID- 9024694
TI  - Bee1, a yeast protein with homology to Wiscott-Aldrich syndrome protein, is
      critical for the assembly of cortical actin cytoskeleton.
AB  - Yeast protein, Bee1, exhibits sequence homology to Wiskott-Aldrich syndrome
      protein (WASP), a human protein that may link signaling pathways to the actin
      cytoskeleton. Mutations in WASP are the primary cause of Wiskott-Aldrich
      syndrome, characterized by immuno-deficiencies and defects in blood cell
      morphogenesis. This report describes the characterization of Bee1 protein
      function in budding yeast. Disruption of BEE1 causes a striking change in the
      organization of actin filaments, resulting in defects in budding and cytokinesis.
      Rather than assemble into cortically associated patches, actin filaments in the
      buds of delta bee1 cells form aberrant bundles that do not contain most of the
      cortical cytoskeletal components. It is significant that delta bee1 is the only
      mutation reported so far that abolishes cortical actin patches in the bud. Bee1
      protein is localized to actin patches and interacts with Sla1p, a Src homology 3
      domain-containing protein previously implicated in actin assembly and function.
      Thus, Bee1 protein may be a crucial component of a cytoskeletal complex that
      controls the assembly and organization of actin filaments at the cell cortex.

PMID- 9024695
TI  - Inhibition of a mitotic motor compromises the formation of dendrite-like
      processes from neuroblastoma cells.
AB  - Microtubules in the axon are uniformly oriented, while microtubules in the
      dendrite are nonuniformly oriented. We have proposed that these distinct
      microtubule polarity patterns may arise from a redistribution of molecular motor
      proteins previously used for mitosis of the developing neuroblast. To address
      this issue, we performed studies on neuroblastoma cells that undergo mitosis but
      also generate short processes during interphase. Some of these processes are
      similar to axons with regard to their morphology and microtubule polarity
      pattern, while others are similar to dendrites. Treatment with cAMP or retinoic
      acid inhibits cell division, with the former promoting the development of the
      axon-like processes and the latter promoting the development of the dendrite-like
      processes. During mitosis, the kinesin-related motor termed CHO1/MKLP1 is
      localized within the spindle midzone where it is thought to transport
      microtubules of opposite orientation relative to one another. During process
      formation, CHO1/ MKLP1 becomes concentrated within the dendrite-like processes
      but is excluded from the axon-like processes. The levels of CHO1/MKLP1 increase
      in the presence of retinoic acid but decrease in the presence of cAMP, consistent
      with a role for the protein in dendritic differentiation. Moreover, treatment of
      the cultures with antisense oligonucleotides to CHO1/MKLP1 compromises the
      formation of the dendrite-like processes. We speculate that a redistribution of
      CHO1/MKLP1 is required for the formation of dendrite-like processes, presumably
      by establishing their characteristic nonuniform microtubule polarity pattern.

PMID- 9024696
TI  - GKAP, a novel synaptic protein that interacts with the guanylate kinase-like
      domain of the PSD-95/SAP90 family of channel clustering molecules.
AB  - The molecular mechanisms underlying the organization of ion channels and
      signaling molecules at the synaptic junction are largely unknown. Recently,
      members of the PSD-95/SAP90 family of synaptic MAGUK (membrane-associated
      guanylate kinase) proteins have been shown to interact, via their NH2-terminal
      PDZ domains, with certain ion channels (NMDA receptors and K+ channels), thereby
      promoting the clustering of these proteins. Although the function of the NH2
      terminal PDZ domains is relatively well characterized, the function of the Src
      homology 3 (SH3) domain and the guanylate kinase-like (GK) domain in the COOH
      terminal half of PSD-95 has remained obscure. We now report the isolation of a
      novel synaptic protein, termed GKAP for guanylate kinase-associated protein, that
      binds directly to the GK domain of the four known members of the mammalian PSD-95
      family. GKAP shows a unique domain structure and appears to be a major
      constituent of the postsynaptic density. GKAP colocalizes and
      coimmunoprecipitates with PSD-95 in vivo, and coclusters with PSD-95 and K+
      channels/NMDA receptors in heterologous cells. Given their apparent lack of
      guanylate kinase enzymatic activity, the fact that the GK domain can act as a
      site for protein-protein interaction has implications for the function of diverse
      GK-containing proteins (such as p55, ZO-1, and LIN-2/CASK).

PMID- 9024697
TI  - Intrinsic neuronal determinants locally regulate extrasynaptic and synaptic
      growth at the adult neuromuscular junction.
AB  - Long-term functional plasticity in the nervous system can involve structural
      changes in terminal arborization and synaptic connections. To determine whether
      the differential expression of intrinsic neuronal determinants affects structural
      plasticity, we produced and analyzed transgenic mice overexpressing the cytosolic
      proteins cortical cytoskeleton-associated protein 23 (CAP-23) and growth
      associated protein 43 (GAP-43) in adult neurons. Like GAP-43, CAP-23 was
      downregulated in mouse motor nerves and neuromuscular junctions during the second
      postnatal week and reexpressed during regeneration. In transgenic mice, the
      expression of either protein in adult motoneurons induced spontaneous and greatly
      potentiated stimulus-induced nerve sprouting at the neuromuscular junction. This
      sprouting had transgene-specific features, with CAP-23 inducing longer, but less
      numerous sprouts than GAP-43. Crossing of the transgenic mice led to dramatic
      potentiation of the sprout-inducing activities of GAP-43 and CAP-23, indicating
      that these related proteins have complementary and synergistic activities. In
      addition to ultraterminal sprouting, substantial growth of synaptic structures
      was induced. Experiments with pre- and postsynaptic toxins revealed that in the
      presence of GAP-43 or CAP-23, sprouting was stimulated by a mechanism that
      responds to reduced transmitter release and may be independent of postsynaptic
      activation. These results demonstrate the importance of intrinsic determinants in
      structural plasticity and provide an experimental approach to study its role in
      nervous system function.

PMID- 9024698
TI  - NH2-terminal deletion of beta-catenin results in stable colocalization of mutant
      beta-catenin with adenomatous polyposis coli protein and altered MDCK cell
      adhesion.
AB  - beta-Catenin is essential for the function of cadherins, a family of Ca2+
      dependent cell-cell adhesion molecules, by linking them to (alpha)-catenin and
      the actin cytoskeleton. beta-Catenin also binds to adenomatous polyposis coli
      (APC) protein, a cytosolic protein that is the product of a tumor suppressor gene
      mutated in colorectal adenomas. We have expressed mutant beta-catenins in MDCK
      epithelial cells to gain insights into the regulation of beta-catenin
      distribution between cadherin and APC protein complexes and the functions of
      these complexes. Full-length beta-catenin, beta-catenin mutant proteins with NH2
      terminal deletions before (deltaN90) or after (deltaN131, deltaN151) the alpha
      catenin binding site, or a mutant beta-catenin with a COOH-terminal deletion
      (delta C) were expressed in MDCK cells under the control of the tetracycline
      repressible transactivator. All beta-catenin mutant proteins form complexes and
      colocalize with E-cadherin at cell-cell contacts; deltaN90, but neither deltaN131
      nor deltaN151, bind alpha-catenin. However, beta-catenin mutant proteins
      containing NH2-terminal deletions also colocalize prominently with APC protein in
      clusters at the tips of plasma membrane protrusions; in contrast, full-length and
      COOH-terminal-deleted beta-catenin poorly colocalize with APC protein. NH2
      terminal deletions result in increased stability of beta-catenin bound to APC
      protein and E-cadherin, compared with full-length beta-catenin. At low density,
      MDCK cells expressing NH2-terminal-deleted beta-catenin mutants are dispersed,
      more fibroblastic in morphology, and less efficient in forming colonies than
      parental MDCK cells. These results show that the NH2 terminus, but not the COOH
      terminus of beta-catenin, regulates the dynamics of beta-catenin binding to APC
      protein and E-cadherin. Changes in beta-catenin binding to cadherin or APC
      protein, and the ensuing effects on cell morphology and adhesion, are independent
      of beta-catenin binding to alpha-catenin. These results demonstrate that
      regulation of beta-catenin binding to E-cadherin and APC protein is important in
      controlling epithelial cell adhesion.

PMID- 9024699
TI  - L-selectin from human, but not from mouse neutrophils binds directly to E
      selectin.
AB  - L-Selectin on neutrophils as well as inducible E- and P-selectin on endothelium
      are involved in the recruitment of neutrophils into inflamed tissue. Based on
      cell attachment assays, L-selectin was suggested to function as a carbohydrate
      presenting ligand for E- and P-selectin. However, previous affinity isolation
      experiments with an E-selectin-Ig fusion protein had failed to detect L-selectin
      among the isolated E-selectin ligands from mouse neutrophils. We show here that L
      selectin from human neutrophils, in contrast to mouse neutrophils, can be
      affinity-isolated as a major ligand from total cell extracts using E-selectin-Ig
      as affinity probe. Binding of human L-selectin to E-selectin was direct, since
      purified L-selectin could be reprecipitated with E-selectin-Ig. Recognition of L
      selectin was abolished by sialidase-treatment, required Ca2+, and was resistant
      to treatment with endoglycosidase F. Binding of L-selectin to a P-selectin-Ig
      fusion protein was not observed. In agreement with the biochemical data, the anti
      L-selectin mAb DREG56 inhibited rolling of human neutrophils on immobilized E
      selectin-Ig but not on P-selectin-Ig. No such inhibitory effect was seen with the
      anti-mouse L-selectin mAb MEL14 on mouse neutrophils. Rolling of E-selectin
      transfectants on purified and immobilized human L-selectin was inhibited by mAb
      DREG56. We conclude that L-selectin on human neutrophils is a major glycoprotein
      ligand among very few glycoproteins that can be isolated by an E-selectin
      affinity matrix. The clear difference between human and mouse L-selectin suggests
      that E-selectin-binding carbohydrate moieties are attached to different protein
      scaffolds in different species.

PMID- 9024700
TI  - Threshold levels of fluid shear promote leukocyte adhesion through selectins
      (CD62L,P,E)
AB  - Leukocyte adhesion through L-selectin to peripheral node addressin (PNAd, also
      known as MECA-79 antigen), an L-selectin ligand expressed on high endothelial
      venules, has been shown to require a minimum level of fluid shear stress to
      sustain rolling interactions (Finger, E.B., K.D. Puri, R. Alon, M.B. Lawrence,
      V.H. von Andrian, and T.A. Springer. 1996. Nature (Lond.). 379:266-269). Here, we
      show that fluid shear above a threshold of 0.5 dyn/cm2 wall shear stress
      significantly enhances HL-60 myelocyte rolling on P- and E-selectin at site
      densities of 200/microm2 and below. In addition, gravitational force is
      sufficient to detach HL-60 cells from P- and E-selectin substrates in the
      absence, but not in the presence, of flow. It appears that fluid shear-induced
      torque is critical for the maintenance of leukocyte rolling. K562 cells
      transfected with P-selectin glycoprotein ligand-1, a ligand for P-selectin,
      showed a similar reduction in rolling on P-selectin as the wall shear stress was
      lowered below 0.5 dyn/cm2. Similarly, 300.19 cells transfected with L-selectin
      failed to roll on PNAd below this level of wall shear stress, indicating that the
      requirement for minimum levels of shear force is not cell type specific. Rolling
      of leukocytes mediated by the selectins could be reinitiated within seconds by
      increasing the level of wall shear stress, suggesting that fluid shear did not
      modulate receptor avidity. Intravital microscopy of cremaster muscle venules
      indicated that the leukocyte rolling flux fraction was reduced at blood
      centerline velocities less than 1 mm/s in a model in which rolling is mediated by
      L- and P-selectin. Similar observations were made in L-selectin-deficient mice in
      which leukocyte rolling is entirely P-selectin dependent. Leukocyte adhesion
      through all three selectins appears to be significantly enhanced by a threshold
      level of fluid shear stress.

PMID- 9024702
TI  - Pathologic diagnosis as the gold standard.
AB  - Issues involving brain tumor diagnosis are discussed in light of the frequently
      observed discrepancies between the diagnoses of general pathologists and
      neuropathologists. Accuracy of diagnoses could be improved if definitions or
      criteria for specific categories of tumors were simplified, clearly established,
      and consensually accepted.

PMID- 9024703
TI  - "One to three" or "four or more"?: selecting patients for postmastectomy
      radiation therapy.
AB  - A review of randomized trials suggesting an improvement in overall patient
      survival with postmastectomy radiation therapy revealed that most patients in
      these studies had three or fewer positive axillary lymph nodes. Therefore, it is
      logical to consider using postmastectomy radiation therapy in all lymph node
      positive patients, not just those with four or more positive lymph nodes.

PMID- 9024701
TI  - Targeted disruption of decorin leads to abnormal collagen fibril morphology and
      skin fragility.
AB  - Decorin is a member of the expanding group of widely distributed small leucine
      rich proteoglycans that are expected to play important functions in tissue
      assembly. We report that mice harboring a targeted disruption of the decorin gene
      are viable but have fragile skin with markedly reduced tensile strength.
      Ultrastructural analysis revealed abnormal collagen morphology in skin and
      tendon, with coarser and irregular fiber outlines. Quantitative scanning
      transmission EM of individual collagen fibrils showed abrupt increases and
      decreases in mass along their axes. thereby accounting for the irregular outlines
      and size variability observed in cross-sections. The data indicate uncontrolled
      lateral fusion of collagen fibrils in the decorindeficient mice and provide an
      explanation for the reduced tensile strength of the skin. These findings
      demonstrate a fundamental role for decorin in regulating collagen fiber formation
      in vivo.

PMID- 9024704
TI  - Sphincter preservation therapy for distal rectal carcinoma: a review.
AB  - BACKGROUND: There has been increasing interest in the use of sphincter-preserving
      therapy for patients with distal rectal carcinomas. The outcomes of conservative
      treatments for early stage rectal carcinoma appear to be comparable to that
      achieved with abdominoperineal resection. METHODS: Retrospective and prospective
      clinical series of patients with distal rectal carcinoma treated by local
      excision alone, local excision with postoperative adjuvant therapy, preoperative
      radiation followed by local excision, or radical circumferential sphincter
      sparing surgeries were reviewed. The local control rates, salvage rates, and
      treatment complications in patients treated by these various methods were
      examined. RESULTS: Patients with T1 distal rectal carcinoma with favorable
      clinical and histopathologic characteristics treated with local excision alone
      had a local control rate of greater than 90% in most series. Postoperative
      chemoradiation improved local control for those with T1 disease with unfavorable
      characteristics, or those with T2 disease. Most T3 patients had failure rates of
      greater than 30% despite adjuvant local and systemic therapy. With high dose
      preoperative radiation, approximately 80% of patients with locally advanced or
      unresectable tumors were able to undergo sphincter-preservation treatment.
      CONCLUSIONS: Patients with favorable T1 rectal carcinoma are likely to be
      adequately treated with local excision alone. Patients with T1 disease with
      unfavorable characteristics as well as T2 patients will benefit from
      postoperative chemoradiation. The use of local therapy in T3 patients needs to be
      carefully considered because these patients are at relatively high risk for local
      recurrence despite adjuvant therapy. Preoperative radiation followed by either
      local excision or radical circumferential sphincter-sparing resections appears
      promising in allowing sphincter preservation in patients with locally advanced
      tumors.

PMID- 9024705
TI  - Assessment of microsatellite alterations in young patients with gastric
      adenocarcinoma.
AB  - BACKGROUND: Genetic factors are probably important in the development of gastric
      carcinoma in young patients (younger than 40 years). The authors investigated
      early onset primary gastric adenocarcinomas for the presence of microsatellite
      instability, which is a phenotypic marker for the hereditary nonpolyposis colon
      carcinoma syndrome. METHODS: DNA was extracted from archival microdissected
      carcinoma and corresponding normal tissue from 10 British gastric carcinoma
      patients age 19 to 39 years at the time of diagnosis. A panel of 12
      microsatellite loci were amplified by fluorescent polymerase chain reaction and
      analyzed using an automated DNA sequencer. RESULTS: There was no evidence of
      microsatellite instability. In contrast, allelic imbalance was recorded at
      D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci.
      CONCLUSIONS: The authors reported ten cases of early onset gastric carcinoma that
      demonstrated allelic imbalance but no evidence of instability at microsatellite
      loci. It is unlikely that defective DNA mismatch repair is important in this
      group of young patients.

PMID- 9024706
TI  - Relationship between the recurrence of hepatocellular carcinoma (HCC) and serum
      alanine aminotransferase levels in hepatectomized patients with hepatitis C virus
      associated cirrhosis and HCC.
AB  - BACKGROUND: The relationship between the recurrence of hepatocellular carcinoma
      (HCC) and the serum alanine aminotransferase (ALT) level was studied in
      hepatectomized patients with hepatitis C virus (HCV)-associated cirrhosis and
      HCC. METHODS: Twenty-six hepatectomized patients with HCV-associated cirrhosis
      and HCC whose resected specimens showed neither portal vein nor hepatic vein
      invasion by HCC histologically were divided into 2 groups: 15 patients who had no
      recurrence 3 years after surgery (Group A) and 11 patients whose disease recurred
      1-3 years after surgery (Group B). The patients' serum ALT levels during this
      period were examined. RESULTS: In Group A, serum ALT generally showed sustained
      low levels < 80 international units (INU) in 12 patients (80%). In contrast, ALT
      levels in Group B showed several peaks or plateaus > 80 INU in all patients
      except 2. The recurrence rate of HCC in the hepatectomized patients with
      sustained low levels of ALT was 14.3% (2 of 14 patients) at 3 years, and was
      significantly lower (P < 0.01) than that in those patients whose ALT levels
      showed several peaks or plateaus > 80 INU (9 of 12 patients; 75.0%). The average
      level of mode of ALT in Group A (48.8 +/- 26.0 INU) was significantly smaller
      than that in Group B (101.1 +/- 47.3 INU) (P < 0.005). CONCLUSIONS: The
      importance of hepatocytic necrosis in the recurrence of HCC in hepatectomized
      patients with cirrhosis and HCC of HCV origin was demonstrated and the
      significance of subsiding hepatic necroinflammatory process in the prevention of
      HCC recurrence suggested.

PMID- 9024707
TI  - 18F-fluorodeoxyglucose positron emission tomography and the prognosis of patients
      with pancreatic adenocarcinoma.
AB  - BACKGROUND: Fluorodeoxyglucose (FDG) detected by positron emission tomography
      (PET) can be used to measure the glycolytic activity of tumor cells. Though the
      prognosis of patients with pancreatic adenocarcinoma is usually poor, a subset of
      patients with good prognoses may be discovered by determining the degree of FDG
      integration into tumors. METHODS: Fourteen patients with histologically proven
      pancreatic adenocarcinoma underwent 18F-FDG PET. The standardized uptake value
      (SUV) of 18F-FDG was calculated, and the patients were divided into high (> or =
      3.0) and low (< 3.0) SUV groups. RESULTS: The two groups were not significantly
      different in terms of age, tumor location and size, staging, and treatment.
      However, analysis by the Kaplan-Meier method revealed that the groups had
      different prognoses (log rank test, P < 0.05). The mean survival of patients with
      high SUV was 5 months, whereas that of patients with low SUV was 14 months. There
      were not strong correlations between the SUVs and tumor size (0.56), serum
      carbohydrate antigen 19-9 (0.39), or carcinoembryonic antigen (0.52).
      CONCLUSIONS: SUV calculated with 18F-FDG can be utilized as a prognostic factor
      for patients with pancreatic adenocarcinoma.

PMID- 9024709
TI  - Energy balance in nonsmall cell lung carcinoma patients before and after surgical
      resection of their tumors.
AB  - BACKGROUND: The purpose of this study was to investigate whether surgical removal
      of a tumor influences energy balance, body weight, and body composition in lung
      carcinoma patients. METHODS: In 53 nonsmall cell lung carcinoma (NSCLC) patients,
      resting energy expenditure (REE, measured by ventilated hood), energy intake (EI,
      determined by diet history), body weight, and body composition (fat free mass
      [FFM], measured by bioelectrical impedance analysis) were all determined before
      tumor resection. In 39 of 53 patients, REE, EI, body weight, and body composition
      were also measured 3, 6, and 12 months after tumor resection. RESULTS: Thirty-six
      of 53 patients (68%) were found to be hypermetabolic. Fourteen patients were
      excluded from the repeated measurements. Patients with curative tumor resection
      (n = 30) showed an increase in body weight over a 1-year period, in contrast to
      patients with tumor recurrence (n = 9), who lost weight (+3.5 vs. -3.6 kg, P <
      0.005). The weight gain was caused predominantly by an increase in fat mass (FM),
      while the weight loss was caused for more than half by a decrease in FFM. Body
      weight was increased in hypermetabolic patients (n = 20) as well as patients with
      normal metabolism (n = 10) 1 year after successful removal of their tumors.
      However, although EI/REE was significantly increased in hypermetabolic patients
      (from 106% to 140%, P < 0.05), it was not changed in patients with normal
      metabolism. CONCLUSIONS: Hypermetabolic NSCLC patients undergoing curative
      resection show an improvement in energy balance caused by both a decrease in REE
      and an increase in EI. This positive energy balance results in weight gain, which
      is caused predominantly by an increase in FM.

PMID- 9024708
TI  - Molecular pathology of primary and metastatic ductal pancreatic lesions: analyses
      of mutations and expression of the p53, mdm-2, and p21/WAF-1 genes in sporadic
      and familial lesions.
AB  - BACKGROUND: The molecular pathology underlying the development and progression of
      ductal pancreatic adenocarcinoma is poorly understood relative to that of other
      major cancers in industrialized societies. The frequency, nature, and
      distribution of p53 abnormalities, their temporal relationship to the metastatic
      and clinicopathologic phenotypes of sporadic and familial pancreatic cancer, and
      their consequent effects on the genetics and expression of critical wild-type p53
      regulated genes (mdm-2 and p21/WAF-1) warrant examination in pancreatic
      adenocarcinoma. This molecular and immunochemical study of the p53, mdm-2, and
      p21/ WAF-1 genes and gene products examined the largest series of nonneoplastic,
      neoplastic, and metastatic ductal pancreatic lesions reported to date in relation
      to clinicopathologic profile. METHODS: Histologically confirmed specimens of
      primary (n = 136) and metastatic (n = 23) sporadic and familial ductal pancreatic
      adenocarcinoma lesions were subjected to immunochemical analyses of p53
      expression in which a panel of 3 antibodies was utilized. A panel of
      nonneoplastic but histologically abnormal pancreatic lesions (n = 77) from
      individuals with varied histories of cigarette smoking were subjected to similar
      immunohistochemical examinations. In addition, 3 specimens from patients with
      chronic pancreatitis, 2 specimens of normal fetal pancreata, and 16 specimens of
      normal adult pancreata were examined as control tissues. Suitable frozen and
      archival microdissected tumor lesions were evaluated for mutations in exons 4-9
      of the p53 gene by single strand conformation polymorphism (SSCP) and dideoxy
      sequencing analyses in which two distinct sets of outer and nested intron-based
      amplification primers were used for each exon. A subset of 25 tumor specimens and
      18 tumor-derived cell lines for which the p53 mutation status was known were
      examined for amplification and/or overexpression of the mdm-2 gene; amplification
      was determined by Southern hybridization and overexpression by
      immunohistochemical and Western blot analyses. Similarly, mutations in the coding
      region of p21/WAF-1 gene were examined by SSCP and DNA sequence analyses, and
      steady-state expression of the p21/WAF-1 protein was assessed by Western blot
      analysis in these subsets of tumors and tumor-derived cell lines. RESULTS:
      Positive ductal nuclear p53 immunostaining was demonstrated in 56% of primary
      tumors and 54% of metastatic lesions. The frequency did not differ significantly
      between sporadic and familial lesions, and immunostaining was not observed in
      ductal, acinar, or islet cell elements of normal pancreata or histologically
      abnormal benign pancreatic lesions from cigarette smokers. A total of 70% of
      tumor samples revealed reproducible SSCP abnormalities for p53; 42% of these were
      found in exons 7 and 8. DNA sequence analysis of cases with greater than 35%
      epithelial cellularity (n = 25) revealed 17 missense mutations, 12 of which were
      transitions. Seventy-five percent of these transitions were of G:C-->A:T type. A
      total of 22% of the p53 mutations identified were microdeletions, along with one
      insertional mutation at exon 8. None of the normal pancreata from sporadic or
      familial lesions revealed germ-line p53 alterations. Moreover, the frequency and
      spectra of p53 alterations exhibited no clear, statistically significant
      association with tumor grade, TNM stage, or patients' cigarette-smoking
      histories. The mdm-2 gene was neither amplified nor overexpressed
      immunochemically in a subset of ductal adenocarcinomas, and there was no clear
      relationship between the p53 mutation status and the status of the mdm-2 gene or
      protein. Similarly, SSCP and DNA sequence analysis of the p21/WAF-1 gene revealed
      only 2 genetic abnormalities in a series of 25 primary tumors and 15 tumor
      derived cell lines; 1 of the cell lines also revealed the absence of
      immunoreactive p21/WAF-1 protein...

PMID- 9024710
TI  - Phase II study of patients with metastatic nonsmall cell carcinoma of the lung
      treated with paclitaxel by 3-hour infusion.
AB  - BACKGROUND: Single-agent chemotherapy produces partial responses in the range of
      7-27% in patients with Stage IV nonsmall cell lung carcinoma (NSCLC). Cisplatin
      based combination regimens have achieved higher response rates but with
      significant toxicity. Two prior studies employing 24-hour infusions of paclitaxel
      showed responses of 21% and 24%. The purpose of this Phase II study was to
      determine the effects of paclitaxel administered by short duration infusions on
      response rate, toxicity, and quality of life (QOL) in patients with NSCLC.
      METHODS: Twenty patients with histologically proven Stage IV NSCLC were enrolled
      in this study. All were treated on an outpatient basis with standard
      premedication followed by paclitaxel 200 mg/m2 infused intravenously over 3
      hours. Treatments were repeated every 21 days for a maximum of 6 cycles. RESULTS:
      The objective response rate was 6/19 (32%; 95% confidence interval, 13-57%). The
      median duration of response was 6.0 months (range, 2-13 months). The median
      survival of the entire group was 6.0 months (range, 2-24+ months), and the 1-year
      survival rate was 22%. Toxicity was mild, with only one hospitalization required
      for treatment of catheter-related thrombosis. Nonresponding patients were found
      to have worsening Functional Assessment of Cancer Therapy (FACT)-G and FACT-L
      scores. Because this was a small clinical study, it did not demonstrate
      consistent improvement in FACT-G or FACT-L in responding patients. CONCLUSIONS:
      Paclitaxel given as a 3-hour infusion is a well-tolerated, active single agent in
      the treatment of Stage IV NSCLC, worthy of further study. Baseline QOL scores
      predicted those more likely to respond to treatment, but changes in QOL status
      did not correlate well with objective response status.

PMID- 9024711
TI  - A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and
      selective aromatase inhibitor, with megestrol acetate in postmenopausal women
      with advanced breast carcinoma. Arimidex Study Group.
AB  - BACKGROUND: Anastrozole is a new oral aromatase inhibitor with highly potent and
      selective activity for the aromatase enzyme. In a Phase III trial, the efficacy
      and tolerability of anastrozole, given in doses of 1 and 10 mg orally once daily,
      and megestrol acetate, given in doses of 40 mg orally 4 times daily, were
      compared in 386 postmenopausal women with advanced breast carcinoma who
      progressed after tamoxifen therapy. METHODS: The trial was randomized, double
      blind for anastrozole, open label for megestrol acetate, parallel group, and
      multicenter. Patients were randomly assigned to receive anastrozole, 1 mg (n =
      128); anastrozole, 10 mg (n = 130); or megestrol acetate (n = 128). The primary
      efficacy measures were time to progression and tumor response; secondary measures
      were time to treatment failure, duration of response, quality of life, and time
      to death. RESULTS: With a median duration of follow-up of 6 months, there was no
      statistical evidence of a difference between either 1 or 10 mg doses of
      anastrozole and megestrol acetate for any efficacy endpoint. According to rigid
      response criteria, 10%, 6%, and 6% of patients in the anastrozole 1 mg,
      anastrozole 10 mg, and megestrol acetate groups, respectively, had an objective
      response (complete response or partial response) and 27%, 24%, and 30% of
      patients in the respective groups had stable disease for a duration of 24 weeks
      or longer. Quality-of-life assessments revealed that anastrozole in a 1-mg dose
      was associated with better physical scores and anastrozole in a 10-mg dose with
      better psychologic scores than megestrol acetate. Both anastrozole and megestrol
      acetate were generally well tolerated. Among anticipated adverse events,
      gastrointestinal disturbance was more common among patients in the anastrozole
      groups, whereas weight gain occurred more frequently among patients in the
      megestrol acetate groups. Weight increases of 5% or more and 10% or more were
      more common among megestrol acetate-treated patients; moreover, patients in this
      group continued to gain weight over time. CONCLUSIONS: Anastrozole, given in
      doses of 1 and 10 mg once daily, represents a well tolerated and effective
      therapeutic option for the treatment of postmenopausal women with advanced breast
      carcinoma who progress after tamoxifen treatment.

PMID- 9024712
TI  - Mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) versus intravenous
      cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in first-line
      chemotherapy for patients with metastatic breast carcinoma: a randomized phase II
      trial.
AB  - BACKGROUND: Previous Phase II studies using the combination of mitoxantrone, 5
      fluorouracil, and high dose leucovorin (NFL) in the treatment of metastatic
      breast carcinoma have shown this regimen to be active and well tolerated. In this
      randomized Phase II study, the authors compared the NFL regimen with a standard
      CMF regimen in the first-line therapy of patients with metastatic breast
      carcinoma. METHODS: One hundred twenty-eight women receiving their first
      chemotherapy for metastatic breast carcinoma were entered into this randomized
      study. Sixty-four patients were treated with NFL: mitoxantrone 12 mg/m2 IV on Day
      1; leucovorin 300 mg IV over 30-60 minutes on Days 1, 2, and 3, immediately
      preceding administration of 5-fluorouracil; and 5-fluorouracil 350 mg/m2 IV bolus
      on Days 1, 2, and 3. Sixty-four patients received CMF: cyclophosphamide 600 mg/m2
      IV on Day 1; methotrexate 40 mg/m2 IV on Day 1; and 5-fluorouracil 600 mg/m2 IV
      on Day 1. Both regimens were repeated at 21-day intervals; responding patients
      received at least 8 courses. RESULTS: Patients treated with NFL had a higher
      response rate than patients treated with the CMF regimen (45% vs. 26%,
      respectively; P = 0.021). Median duration of response was 9 months with NFL and 6
      months with CMF (P = 0.10); 11 patients had long responses (>12 months) with NFL
      versus 4 patients with CMF (P = 0.06). Median survival was similar for both
      groups. Both regimens were well tolerated, with infrequent Grade 3 or 4
      toxicities. CONCLUSIONS: NFL is an active, well-tolerated regimen for the
      treatment of metastatic breast carcinoma; it produced a higher response rate than
      the CMF regimen used in this study. Although more intense CMF regimens or
      regimens containing doxorubicin would likely increase the response rate, they
      would almost certainly do so with the consequence of greater toxicity as compared
      with NFL. NFL is an excellent initial palliative treatment option for elderly
      patients or patients who have exhibited poor tolerance for other chemotherapy
      regimens.

PMID- 9024713
TI  - Expression of scatter factor and c-met receptor in benign and malignant breast
      tissue.
AB  - BACKGROUND: Scatter factor (SF), also known as hepatocyte growth factor, is an
      angiogenic cytokine that stimulates epithelial cell motility and invasion. Its
      receptor is a transmembrane tyrosine kinase encoded by the c-met protooncogene.
      Several prior experimental and clinical studies have suggested that SF might play
      a role in the development and progression of breast carcinoma. To investigate the
      possible involvement of SF and c-met in the evolution of breast carcinoma, the
      authors studied their expression in sections of human breast tissue. METHODS: A
      variety of paraffin embedded tissue specimens (of normal breast tissue tissue,
      benign hyperplasia, ductal carcinoma-in-situ [DCIS], and invasive ductal
      carcinoma) from 125 patients were immunoperoxidase-stained using specific
      antisera against SF and c-met. The staining intensities of epithelial mammary
      cells were scored semiquantitatively, and the staining scores were analyzed as a
      function of tissue type. In addition, in situ hybridization to detect SF mRNA was
      performed for a small number of cancer sections. RESULTS: Specific SF staining
      was observed in tumor cells, normal cell types (epithelium and vascular smooth
      muscle), and acellular stroma, whereas c- met staining was observed in tumor
      cells and normal cell types but not in stroma. Analysis of the staining scores of
      epithelial mammary cells revealed several patterns: (1) SF and c-met staining
      scores each increased in the following order: normal breast/benign hyperplasias
      (lowest) --> DCIS (higher) --> invasive carcinoma (highest); (2) normal-appearing
      mammary ducts and lobules in invasive cancer sections showed less SF and c-met
      staining than tumor cells in the same specimens but more staining than normal
      ducts and lobules in sections of normal breast tissue and benign hyperplasia; (3)
      within the DCIS and invasive cancer groups, SF and c-met staining scores were
      correlated; and (4) among 40 consecutive cases of DCIS, higher levels of SF and c
      met staining showed a trend toward association with other features suggestive of
      aggressive tumor biology (comedo histology, high nuclear grade, p53 positivity,
      and bcl-2 negativity). In situ hybridization analysis revealed that the same cell
      types that expressed SF protein (including tumor cells) also expressed SF mRNA
      transcripts. CONCLUSIONS: SF and c-met are overexpressed in breast carcinoma as
      compared with benign breast tissue, and they tend to be coexpressed in cancerous
      tissue. These findings are consistent with the idea that the SF:c-met
      ligand:receptor pair may have a role in breast carcinoma progression.

PMID- 9024714
TI  - Lymph node negative invasive breast carcinoma 1 centimeter or less in size
      (T1a,bNOMO): clinicopathologic features and outcome.
AB  - BACKGROUND: Patients with lymph node negative invasive breast carcinomas < or = 1
      cm in size have a low recurrence rate and may be spared adjuvant therapy.
      Reliable prognostic features will help physicians design appropriate treatment
      for these patients. METHODS: The clinicopathologic features, prognostic marker
      profiles, and clinical outcomes of 88 T1a,bN0M0 carcinomas in 87 patients who
      presented between 1975 and 1990 were studied. The size of each tumor was
      determined by direct measurement of histologic sections. The median follow-up was
      7.8 years (range, 4-15 years). The characteristics of tumors diagnosed between
      1975 and 1983 and between 1984 and 1990 were also compared. RESULTS: Before 1984,
      the majority of patients presented with palpable mass lesions, whereas from 1984
      on, more patients presented with mammographic abnormalities. However, no
      significant differences in the pathologic features of tumors were observed
      between the two periods. There were only 3 locoregional recurrences (3%) and 4
      distant recurrences (5%). Palpable tumors had worse prognoses than
      mammographically detected lesions (P = 0.02). Histologic grade, lymphatic
      invasion, hormone receptors, Ki-67 antigen, and bcl-2 expression were significant
      univariate prognostic indicators. The small number of patients in the series
      precluded multivariate analysis. None of the 43 patients (49%) with tumors < or =
      0.5 cm, or of histologic and nuclear Grade 1, or of favorable histologic types
      developed recurrences; and their outcomes were significantly better than those of
      other patients (P = 0.013). Tumors originally classified as T1b, but which
      exceeded 1 cm on review and were excluded from the study, had a significantly
      higher distant recurrence rate (23%) than bona fide T1a,b carcinomas (P = 0.03).
      CONCLUSIONS: T1a,bN0M0 carcinomas have a low recurrence rate, especially those
      tumors < or = 0.5 cm, or of low histologic or nuclear grade, or of favorable
      histologic type. The high recurrence among patients with tumors initially
      understaged as T1a,b carcinoma underscores the importance of accurately
      determining tumor size.

PMID- 9024715
TI  - Tumor angiogenesis correlates with progression after radical prostatectomy but
      not with pathologic stage in Gleason sum 5 to 7 adenocarcinoma of the prostate.
AB  - BACKGROUND: Prior studies have suggested that tumor angiogenesis (microvessel
      density [MVD]) may be of prognostic significance in patients with prostate
      carcinoma. METHODS: The authors examined the relationship of MVD in intermediate
      grade prostate carcinomas with stage at radical prostatectomy (RP) and
      progression after RP. For the former group, 109 RP specimens with Gleason sums of
      6 and 7 were studied: 34 organ-confined tumors, 37 with capsular penetration, 21
      with seminal vesicle involvement, and 17 with pelvic lymph node metastasis. For
      the latter group, 87 RP specimens were studied that had a Gleason sum of 5 to 7
      for which the patients underwent follow-up of at least 7 years or until
      progression. Thirty-seven patients (43%) progressed at a mean of 3.5 years
      (range, 1-8 years). Representative sections of each tumor were stained for CD31
      and "hot spot" microvessels were quantitated in a 3.14-mm2 area. RESULTS: In the
      first arm, there was no relationship between MVD and stage at RP. In the second
      arm, the mean MVD in tumors that progressed was significantly higher than in
      nonprogressors (43.0 +/- 26.1 vs. 29.0 +/- 13.1; P < 0.0001 by Wilcoxon-Gehan
      statistic). MVD and Gleason sum were independent statistically significant
      predictors of progression (MVD, P < 0.0001; Gleason sum, P < 0.0001 by Cox
      proportional hazards model). CONCLUSIONS: MVD is an independent significant
      predictor of progression after RP for tumors with a Gleason sum of 5 to 7.
      Because these comprise the majority of RP specimens, it is this group for which
      discrimination of biologic potential is most needed. Angiogenesis may be useful
      in the prognostic stratification of patients beyond that possible using stage and
      grade alone.

PMID- 9024716
TI  - Significance of cyclin D1 overexpression in transitional cell carcinomas of the
      urinary bladder and its correlation with histopathologic features.
AB  - BACKGROUND: Genetic alterations leading to neoplastic transformation of the
      urothelium are likely to involve the activation of oncogenes and loss of
      functional tumor suppressor genes. Cyclin D1 has been implicated as a putative
      protooncogene whereas mutations of the p53 gene occur frequently in invasive
      transitional cell carcinomas (TCCs) of the urinary bladder. In this study, cyclin
      D1 overexpression and nuclear accumulation of p53 were evaluated and the results
      correlated with histopathologic features. METHODS: TCCs of the urinary bladder
      from 161 surgical procedures were evaluated for cyclin D1 overexpression and
      nuclear accumulation of p53. Results were correlated with tumor grade, T
      classification, and papillary status. Topologic distributions of cyclin D1, p53,
      and proliferating cellular nuclear antigen (PCNA) were evaluated. Northern blot
      analysis was performed on selected specimens. RESULTS: Overexpression of cyclin
      D1 was observed in 47% (24 of 51) of Grade 1 TCCs and 20% (13 of 65) of Grade 2
      TCCs but in no Grade 3 TCCs. Approximately 34% (14 of 41) of Ta classified TCCs
      and 21% (13 of 63) of T1 classified TCCs were immunoreactive for cyclin D1
      whereas none of the TCCs beyond T1 was immunoreactive. Overexpression of cyclin
      D1 was observed only in papillary type TCCs. Results of Northern blot analysis
      for cyclin D1 were comparable to those of immunohistochemistry. CONCLUSIONS: The
      observed significant relation between cyclin D1 overexpression and tumor grade/T
      classification suggests that cyclin D1 may be a useful biologic marker for
      biopsied materials or urine cytology specimens. The prognostic significance of
      cyclin D1 overexpression in TCCs remains to be determined.

PMID- 9024717
TI  - Central neurocytomas.
AB  - BACKGROUND: This analysis was performed to examine the outcome of patients with
      histologically confirmed central neurocytomas. METHODS: Thirty-two patients with
      histologically confirmed central neurocytomas were evaluated retrospectively.
      Patients were treated with various combinations of surgery, chemotherapy, and
      radiotherapy (RT). Follow-up ranged from 2.3 to 15.3 years (median, 4.7 years).
      RESULTS: The overall 5-year survival and local control rates were 81% and 79%,
      respectively. No patient developed metastases. The 5-year local control rate was
      70% for patients undergoing subtotal resection (STR) and 100% for those
      undergoing gross total resection (GTR) (P = 0.08). The 5-year survival rate was
      77% for patients undergoing STR and 90% for those undergoing GTR (P = 0.44). The
      effect of RT was evaluated for patients undergoing STR. The 5-year local control
      rate was 100% for patients who received RT after STR compared with 50% for those
      who did not (P = 0.02). The 5-year survival rate was 88% for patients who
      received RT after STR compared with 71% for those who did not (P = 0.3). Three
      patients received salvage RT for local progression after resection. All were
      alive and free of disease 1 to 6 years after RT. CONCLUSIONS: GTR results in a
      very high likelihood of local control and survival. Postoperative RT appears to
      improve local control rates significantly for patients who have undergone STR.
      The overall prognosis of patients with central neurocytomas is quite favorable,
      with an actuarial 5-year survival rate of 81%.

PMID- 9024718
TI  - Diagnostic discrepancies and their clinical impact in a neuropathology referral
      practice.
AB  - BACKGROUND: During the course of their neuropathology practice, the authors
      received cases to review in consultation. In some cases, the patients came to the
      authors' hospital for therapy; in others, the primary pathologists requested a
      consultation. Because changes in diagnosis might significantly alter patient
      management, protocol entry, care costs, or the potential for physician liability,
      the authors determined the frequency and degrees of their disagreements with the
      original diagnoses submitted to them. METHODS: The authors reviewed the first 500
      brain or spinal cord biopsy cases that were submitted to their neuropathology
      consultation service for a second opinion in 1995. Disagreements were coded into
      10 categories, but were grouped for this analysis as follows: serious (having
      immediate significance for therapy or intervention), less serious but potentially
      substantial (calling for a change in type or grade of glioma), minor (adding or
      deleting information), and those in which the authors made the first diagnosis
      themselves. RESULTS: There was some degree of disagreement between the original
      and review diagnoses in 214 (42.8%) of the 500 cases. Disagreements were counted
      as serious in 44 cases (8.8%), less serious but substantial in 96 cases (19.2%),
      and minor in 50 cases (10.0%); the authors made the first diagnosis in 24 cases
      (4.8%). CONCLUSIONS: Clinically important diagnostic errors that can affect
      immediate patient care decisions occur in a substantial number of brain and
      spinal cord biopsy cases. Thus, seeking expert neuropathology consultation is
      prudent and cost-effective for pathologists who are less experienced with these
      types of cases. Cost savings in case management might result from confirmation of
      diagnosis before definitive therapy is administered to the patients. The rates of
      discrepancy between original diagnoses and second opinions in other
      subspecialties of pathology should be examined.

PMID- 9024720
TI  - An analysis of 8305 cases of carcinoid tumors.
AB  - BACKGROUND: Carcinoid tumors are unusual and most reports are anecdotal or
      limited in number. A series of 2837 cases was published in 1975. No recent large
      series is available. METHODS: The authors evaluated 5468 cases identified by the
      Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer
      Institute (NCI) from 1973 to 1991 together with 2837 carcinoid cases previously
      registered by 2 earlier NCI programs. To the authors' knowledge, the 8305
      carcinoid tumors analyzed represent the largest current epidemiology series to
      date. RESULTS: The most frequent sites for carcinoids were the gastrointestinal
      (GI) tract (73.7%) and the bronchopulmonary system (25.1%). Within the GI tract,
      most occurred in the small bowel (28.7%), appendix (18.9%), and rectum (12.6%).
      For all sites, age-adjusted incidence rates were highest in African American
      males (2.12 per 100,000 population per year). Associated noncarcinoid tumors were
      frequent in conjunction with small intestinal (16.6%), appendiceal (14.6%), and
      colonic carcinoids (13.1%). The highest percentage of nonlocalized lesions were
      noted for pancreatic (76.1%), colonic (71.2%), and small intestinal carcinoids
      (70.7%) and this corresponded to their poor 5-year survival rates (34.1%, 41.6%,
      and 55.4%, respectively). The best 5-year survival rates were recorded for
      appendiceal (85.9%), bronchopulmonary (76.6%), and rectal carcinoids (72.2%).
      These exhibited invasive growth or metastatic spread in only 35.4%, 27.2%, and
      14.2% of cases, respectively. CONCLUSIONS: Carcinoids appear to have increased in
      incidence in the past 20 years. In part, this may be due to different surgical
      rules of the various registries, improved diagnostic technology, and increased
      awareness. A cumulative analysis of all types of carcinoid tumors in the SEER
      group indicates that in 45.3% metastases are already evident at the time of
      diagnosis. The overall 5-year survival rate of all carcinoid tumors regardless of
      site was 50.4% +/- 6.4%.

PMID- 9024719
TI  - Pituitary carcinoma: a clinicopathologic study of 15 cases.
AB  - BACKGROUND: Pituitary carcinomas are rare adenohypophysial neoplasms, the
      definition, diagnosis, therapy, and prognosis of which are controversial.
      METHODS: Pituitary carcinomas were defined as primary adenohypophysial neoplasms
      with documented craniospinal and/or systemic metastases. The authors report a
      clinicopathologic study of 15 examples examined by light microscopy,
      immunohistochemistry, and image analysis. Both proliferative activity and p53
      tumor suppressor gene expression were studied. RESULTS: The study group consisted
      of 15 patients, including 8 males and 7 females ranging in age from 34-71 years
      (mean, 56 years). Of these patients, seven had adrenocorticotropic hormone (ACTH)
      producing tumors (four in the context of Nelson's syndrome), seven had prolactin
      producing tumors, and one had a nonfunctioning tumor. No evidence of diabetes
      insipidus was seen in any case. Fourteen tumors were initially considered
      macroadenomas. Of the ten cases for whom tumor extent was known, all had invasive
      tumors. The interval from the initial diagnosis of adenoma to that of carcinoma
      ranged from 0.3 to 18.0 years (mean, 6.6 years; median, 5.0 years); the longest
      mean interval (15.3 years) occurred for patients with Nelson's syndrome. The
      latency was twice as long for ACTH-producing tumors as for prolactin (PRL) cell
      tumors (9.5 vs. 4.7 years). All carcinomas showed a greater tendency toward
      systemic metastasis than craniospinal metastasis; the rate of systemic metastasis
      was 71% for PRL cell tumors and 57% for ACTH-producing tumors. Thirteen percent
      of tumors showed both patterns of metastasis. Fully 50% of primary tumors and the
      majority of metastases showed nuclear pleomorphism and/or hyperchromasia. The
      mean mitotic, MIB-1, and proliferating cell nuclear antigen indices for primary
      tumors and metastases were as follows: 2/10 high-power field (hpf), 2.6% and 11%,
      respectively; 6/10 hpf, 7.8% and 16%, respectively. Staining for p53 protein was
      noted in 57% of primary tumors and 88% of metastatic tumors; a relative increase
      in p53 expression in metastases was noted in 83%. All but one of the primary and
      metastatic tumors were aneuploid. The most common treatments were radiation
      therapy and, for PRL cell carcinomas, dopamine agonist administration. Both
      treatments provided only palliation. Eighty percent of the patients died of
      metastatic disease 7 days to 8 years after the diagnosis of carcinoma; of these,
      66% died within 1 year. At last follow-up, 20% of patients were alive with
      metastases 9-18 months after diagnosis. CONCLUSIONS: Nearly all pituitary
      carcinomas present as functioning, microscopically atypical or mitotically
      active, invasive macroadenomas. By definition, after an interval related to their
      immunotype, all metastasize. The tumors show a greater tendency toward systemic
      metastasis than craniospinal metastasis and are associated with poor prognosis.
      Radiation and dopamine agonist therapy generally provide only palliation.
      Proliferation indices and p53 expression tend to be higher in metastases than in
      primary tumors. The current definition of pituitary carcinoma requires the
      demonstration of metastasis; however, high mitotic and MIB-1 labeling indices as
      well as p53 immunoreactivity suggest the diagnosis and appear to be of prognostic
      significance. A redefinition of aggressive pituitary tumors is proposed--one that
      facilitates the recognition of tumors prone to metastasis.

PMID- 9024721
TI  - Incidence and morbidity of cholelithiasis in patients receiving chronic
      octreotide for metastatic carcinoid and malignant islet cell tumors.
AB  - BACKGROUND: Octreotide, a long-acting somatostatin analogue, has demonstrated
      clinical utility in patients with carcinoid syndrome and malignant islet cell
      tumors of the pancreas. Prior studies have reported a greater than expected
      incidence of cholelithiasis in patients treated with octreotide for acromegaly.
      This study attempted to determine the incidence and morbidity of cholelithiasis
      in a group of patients with metastatic carcinoid or malignant pancreatic islet
      cell tumors who were receiving chronic therapy with octreotide. METHODS: Forty
      four of 55 patients on investigational protocols with octreotide were eligible
      for chart review; 10 patients were excluded due to prior cholecystectomy and 1
      patient due to asymptomatic cholelithiasis at presentation. Patients fell into
      three treatment groups. The low dose (LD) group was comprised of 17 patients
      receiving 150 microg of subcutaneous octreotide 3 times a day. Twenty-one
      patients received high dose (HD) therapy comprised of 500 microg given 3 times a
      day. The low dose-high dose (LD-HD) group was comprised of 6 patients who had
      their dose escalated from 150 microg to 225-500 microg of octreotide 3 times a
      day. RESULTS: The overall incidence of cholelithiasis and/or gallbladder sludge
      was found to be 52.3% in all 3 treatment groups. Three of the 44 patients (6.8%)
      had symptomatic disease requiring emergency cholecystectomy. Five other patients
      underwent elective or incidental gallbladder surgery. The incidence of
      cholelithiasis in the LD, LD-HD, and HD groups was 35.3%, 66.6%, and 61.9%,
      respectively. The incidence of acute cholecystitis in the three groups was 11.8%,
      0%, and 4.8%, respectively. CONCLUSIONS: Although greater than 50% of patients
      receiving octreotide developed cholelithiasis, a much smaller percentage of
      patients had symptomatic gallbladder disease. Patients receiving chronic
      octreotide treatment require monitoring for the development of gallstones.
      However, prophylactic cholecystectomy is not indicated, unless it is performed in
      conjunction with bowel resection or cytoreductive hepatic surgery.

PMID- 9024722
TI  - The frequency and clinical course of cognitive impairment in patients with
      terminal cancer.
AB  - BACKGROUND: Cognitive disorders are among the most frequent psychiatric
      complications of advanced cancer. This study reviews the frequency and clinical
      course of cognitive failure in patients with advanced cancer admitted to a
      palliative care unit. METHODS: In this retrospective study, all 348 patients
      admitted to the Edmonton General Palliative Care Unit over a period of 26 months
      were reviewed. The Mini-Mental State Examination (MMSE) was used as a screening
      tool to assess cognitive functioning and was performed on all patients at the
      time of admission and once to twice weekly thereafter. In all cases, when
      cognitive failure was diagnosed, a standardized management protocol was followed.
      RESULTS: Three hundred and twenty-one patients (92.2%) were evaluable. A total of
      1441 MMSEs were performed. Each patient underwent an average of 4.7 +/- 4.26
      MMSEs and every patient underwent an MMSE every 4.9 (+/- 3.3) days (median, 3.6
      days). The mean age (standard deviation [SD]) of the study group was 64.2 (+/-
      12) and the mean +/- SD (median) length of stay was 27 +/- 22 (20.5) days. Two
      hundred and thirty-one patients (71%) died on the unit. One hundred and forty-two
      patients (44%) had abnormal MMSE scores (MMSE < 0.8) on admission, whereas 176
      patients (55%) had abnormal MMSE scores at the time of death or discharge. Of the
      231 patients who died on the unit, 157 (68%) had abnormal MMSE scores prior to
      death. There was no significant difference in the first MMSE between patients who
      died and those who were discharged (P = 0.16). Of the 240 patients who underwent
      2 or more MMSEs, 99 (41%) had normal initial and final MMSEs, 54 (23%) had normal
      initial MMSE scores but abnormal final scores, and 62 (26%) had both initial and
      final abnormal scores. Of the 87 surviving patients with an MMSE score of < 0.8
      on admission, 25 (29%) had initial abnormal and final normal scores, indicating
      an improvement. Twelve of these 25 patients (48%) with abnormal initial scores
      but normal final scores were discharged versus 52 of 99 patients (53%) with
      normal initial and final MMSE scores (P > 0.2). Of 124 patients with normal final
      MMSE scores, 64 (52%) were discharged versus 16 of 116 patients (14%) who had
      abnormal MMSE final scores (P < 0.0001). CONCLUSIONS: These data suggest that
      cognitive screening should take place in patients with advanced cancer because
      cognitive failure is highly prevalent in this population, is reversible in a
      significant proportion of patients, and the presence of sustained cognitive
      impairment is a poor prognosticator for discharge. However, these results need to
      be confirmed in prospective studies.

PMID- 9024723
TI  - Cutaneous melanoma in patients with sarcoma.
AB  - BACKGROUND: The authors became interested in an association between cutaneous
      melanoma and sarcoma when they reviewed their experience with other malignancies
      occurring in patients with a diagnosis of sarcoma. METHODS: The authors
      identified 48 patients with both melanoma and bone or soft tissue sarcoma (STS)
      by a computer search of all sarcoma patients entered into their institution's
      cancer registry between 1943 and 1996 who had an additional diagnosis of
      melanoma. The medical records were reviewed and clinical and pathologic data
      collected. RESULTS: The median age at diagnosis was 46 years for patients with
      melanoma and 50 years for patients with sarcoma, which was consistent with
      population-based data. Among patients with STS (n = 41), malignant peripheral
      nerve sheath tumors (MPNT) were more common in patients with both diagnoses (5 of
      41; 13%) when compared with all adults with STS admitted to the study center
      between 1982 to date (125 of 2901; 4%; P < 0.05). Liposarcoma occurred in only 1
      patient with both melanoma and STS (1 of 41; 2%), despite the fact that it was
      the most common histologic diagnosis in all adults with STS (625 of 2901; 22%; P
      < 0.001). The anatomic site of STS was more commonly visceral (11 of 41; 27%)
      when compared with all adults with STS (424 of 2901; 15%; P < 0.05). A positive
      family history of cancer was noted in 50% of the patients, and 25% of patients
      had a third primary tumor. CONCLUSIONS: Although a distinct "melanoma/sarcoma"
      syndrome was not identified, MPNT as well as visceral sarcomas were more common
      than expected in this study. The authors also noted strong family histories of
      cancer as well as additional primary malignancies in patients with melanoma and
      sarcoma, suggesting a predisposition toward cancer.

PMID- 9024724
TI  - Proliferation index as a predictor of prognosis in malignant gliomas of
      childhood.
AB  - BACKGROUND: The prognosis for children with high grade gliomas remains somewhat
      unpredictable because histologic features alone provide an imperfect assessment
      of the biologic behavior of a given lesion. Whereas some patients experience
      prolonged disease control after surgery and adjuvant therapy, others with lesions
      that appear comparable exhibit rapid disease progression and death. METHODS:
      Because proliferative activity may provide a potential correlate of biologic
      aggressiveness, the authors examined the relationship between MIB-1 labeling
      index and outcome in a series of 29 archival pediatric malignant nonbrainstem
      gliomas from patients treated consecutively at the study institution between 1975
      and 1992, in which clinical, histologic, diagnostic, and therapeutic parameters
      were previously defined. Three patients who died perioperatively were excluded
      from outcome analyses. All tumors were rereviewed by two neuropathologists and
      classified as Grade 3 or 4 lesions based on contemporary guidelines. RESULTS:
      Among the specimens from the 26 patients who survived the perioperative period, a
      striking difference in outcome was apparent between tumors with MIB-1 indices <
      12 (n = 10) and those with indices > 12 (n = 16). Median progression free
      survival was >48 months in the low MIB-1 group compared with only 6 months in the
      high MIB-1 group (P = 0.014, rank-sum test). Median overall survival was >48
      months in the low MIB-1 group compared with only 16 months in the high MIB-1
      group (P = 0.012). MIB-1 index remained associated with survival after taking
      into account the effect of resection extent, which also correlated strongly with
      outcome in this cohort. Although MIB-1 index was associated with histopathologic
      grade (Grade 3: 11.9 +/- 9.7 vs. Grade 4: 27.3 +/- 19.0; P = 0.015, Fisher's
      exact test), it proved to be a much stronger predictor of outcome than histology.
      CONCLUSIONS: MIB-1 index may supplement routine histologic classification as a
      means for improving the accuracy of predicting the biologic behavior of childhood
      malignant gliomas and may provide a basis for stratifying patients in future
      malignant glioma studies and refining therapeutic decision-making.

PMID- 9024725
TI  - Artificial neural networks improve the accuracy of cancer survival prediction.
AB  - BACKGROUND: The TNM staging system originated as a response to the need for an
      accurate, consistent, universal cancer outcome prediction system. Since the TNM
      staging system was introduced in the 1950s, new prognostic factors have been
      identified and new methods for integrating prognostic factors have been
      developed. This study compares the prediction accuracy of the TNM staging system
      with that of artificial neural network statistical models. METHODS: For 5-year
      survival of patients with breast or colorectal carcinoma, the authors compared
      the TNM staging system's predictive accuracy with that of artificial neural
      networks (ANN). The area under the receiver operating characteristic curve, as
      applied to an independent validation data set, was the measure of accuracy.
      RESULTS: For the American College of Surgeons' Patient Care Evaluation (PCE) data
      set, using only the TNM variables (tumor size, number of positive regional lymph
      nodes, and distant metastasis), the artificial neural network's predictions of
      the 5-year survival of patients with breast carcinoma were significantly more
      accurate than those of the TNM staging system (TNM, 0.720; ANN, 0.770; P <
      0.001). For the National Cancer Institute's Surveillance, Epidemiology, and End
      Results breast carcinoma data set, using only the TNM variables, the artificial
      neural network's predictions of 10-year survival were significantly more accurate
      than those of the TNM staging system (TNM, 0.692; ANN, 0.730; P < 0.01). For the
      PCE colorectal data set, using only the TNM variables, the artificial neural
      network's predictions of the 5-year survival of patients with colorectal
      carcinoma were significantly more accurate than those of the TNM staging system
      (TNM, 0.737; ANN, 0.815; P < 0.001). Adding commonly collected demographic and
      anatomic variables to the TNM variables further increased the accuracy of the
      artificial neural network's predictions of breast carcinoma survival (0.784) and
      colorectal carcinoma survival (0.869). CONCLUSIONS: Artificial neural networks
      are significantly more accurate than the TNM staging system when both use the TNM
      prognostic factors alone. New prognostic factors can be added to artificial
      neural networks to increase prognostic accuracy further. These results are robust
      across different data sets and cancer sites.

PMID- 9024726
TI  - Ischemic-like ST-segment changes during Holter monitoring in patients with angina
      pectoris and normal coronary arteries but negative exercise testing.
AB  - To evaluate whether Holter electrocardiographic monitoring may improve the
      detection of ST-segment depression in patients with anginal chest pain and normal
      coronary arteries, we performed symptom-limited exercise testing and 24-hour
      Holter monitoring in a group of 38 such patients (27 women, age 54 +/- 8 years).
      Patients were divided into 2 groups:group X1 included 28 patients with and group
      X2 10 patients without significant ST-segment depression during exercise testing.
      There were no significant differences between the 2 groups in age, gender,
      characteristics of chest pain, exercise duration, heart rate (HR), and blood
      pressure at peak exercise, but anginal pain during exercise testing was reported
      by 10 patients of group X1 (36%) and 9 of group X2 (90%) (p <0.01). Episodes of
      ST-segment depression on Holter monitoring were found in 17 patients of group X1
      (61%) and in 5 patients of group X2 (50%) (p = NS). There were no differences
      between the 2 groups in daily number of ST episodes (3.6 +/- 4 vs 2.8 +/- 5
      episodes per patient), symptomatic episodes (8% vs 18%), and duration of the
      episodes. On average, HR increased significantly, in a similar way, from 15
      minutes before ST-segment depression to 1-mm ST in both groups, and its value at
      the onset of ischemia was similar in the 2 groups (102 +/- 22 vs 109 +/- 18
      beats/min, p = NS). Finally, HR at 1-mm ST during Holter monitoring was
      significantly lower than that observed at 1-mm ST during exercise testing (127 +/
      16 beats/min, p < or = 0.01) in group X1, and it was also lower than that
      observed at peak exercise (136 +/- 22 beats/min, p < or = 0.01) in group X2. In
      conclusion, Holter monitoring can significantly increase the detection of ST
      segment depression in patients with anginal pain and normal coronary arteries,
      indicating a cardiac, although not necessarily ischemic, origin of the pain.
      Indeed, 50% of our patients with negative symptom-limited exercise testing showed
      spontaneous ST changes, compatible with transient myocardial ischemia, during
      daily activities. Differences in the response of coronary microvascular tone to
      exercise testing and to stimuli operating during daily life are likely to play a
      significant role in determining these findings.

PMID- 9024727
TI  - Comparison of dobutamine stress echocardiography and 99m-technetium sestamibi
      SPECT myocardial perfusion scintigraphy for predicting extent of coronary artery
      disease in patients with healed myocardial infarction.
AB  - This study compares the value of dobutamine stress echocardiography and 99m
      technetium methoxyisobutyl-isonitrile (MIBI) single-photon emission computed
      tomography (SPECT) in the assessment of extent and location of coronary narrowing
      in patients with healed myocardial infarction. Dobutamine (up to 40 microg/kg/
      min)-atropine (up to 1 mg) stress echocardiography (DSE) in conjunction with MIBI
      SPECT was performed in 72 patients (52 men, mean age 57 +/- 11 years) with healed
      myocardial infarction referred for evaluation of myocardial ischemia. Ischemia
      was defined as new or worsened wall motion abnormalities at DSE and reversible
      perfusion defects at MIBI SPECT. Significant stenosis (> or = 50% luminal
      diameter stenosis) of the infarct-related artery was detected in 45 patients and
      of other coronary arteries in 22 patients. Sensitivity and specificity of remote
      ischemia for diagnosis of remote coronary stenosis were 68% (95% confidence
      interval [CI] 57 to 80) and 93% (CI 86 to 99) for DSE, and 64% (CI 52 to 76), and
      90% (CI 83 to 98) for MIBI SPECT, respectively. The positive predictive value and
      specificity of peri-infarction ischemia for the diagnosis of infarct-related
      artery stenosis were 89% (CI 81 to 97) and 82% (CI 73 to 92) for DSE, and 87% (CI
      79 to 95) and 82% (CI 73 to 92) for SPECT, respectively. The agreement between
      both techniques was higher for the diagnosis of remote than peri-infarction
      ischemia (84% vs 66%, p = 0.02). It is concluded that in patients with myocardial
      infarction undergoing dobutamine stress testing, both echocardiography and MIBI
      SPECT are clinically useful methods for the diagnosis of remote and infarct
      related coronary artery stenosis.

PMID- 9024728
TI  - Comparison of stenting and balloon angioplasty for narrowings in aortocoronary
      saphenous vein conduits in place for more than five years.
AB  - To compare the 1 year outcome of Palmaz-Schatz stent implantation versus balloon
      angioplasty for treatment of obstructive lesions in saphenous vein grafts, we
      combined databases from the Palmaz-Schatz vein graft stent registry and the
      coronary angioplasty arm of the Coronary Angioplasty Versus Excisional
      Atherectomy Trial II (CAVEAT II) for comparison of baseline characteristics,
      procedural variables, in-hospital events and 1-year composite end point of death,
      Q-wave myocardial infarction, and repeat target vessel revascularization. De novo
      graft lesions not involving the ostia were treated with stent implantation in 377
      patients and with coronary angioplasty in 156 patients. The patients were
      comparable in age, coronary risk profile, interval from bypass surgery (9 +/- 4
      years), and reference vessel diameter. The in-hospital composite end point of
      death, myocardial infarction, and emergency revascularization was lower in the
      stent group (10%) than in the angioplasty cohort (17%) (p = 0.059). At 1 year,
      the patients in the stent group had a markedly lower incidence of the composite
      end point of death, myocardial infarction, or revascularization (23% vs 45%, p
      <0.001). In this nonrandomized comparison with balloon angioplasty, the treatment
      of lesions in saphenous vein grafts appears to be favorably influenced by Palmaz
      Schatz stent implantation, in terms of in-hospital events and clinical restenosis
      at 1 year follow-up.

PMID- 9024729
TI  - New criteria for the diagnosis of healed inferior wall myocardial infarction in
      patients with left bundle branch block.
AB  - The diagnosis of healed inferior myocardial infarction (MI) in patients with left
      bundle branch block (LBBB) is difficult because there are no established
      criteria. To develop criteria, we retrospectively examined the electrocardiograms
      of 166 patients with complete LBBB who had either normal images (normals) or an
      isolated, unequivocal inferior MI on delayed stress thallium imaging. Diagnostic
      Q waves were defined as a significant Q or QS of at least 30-ms duration.
      Diagnostic T-wave inversion was defined as complete T inversion or biphasic waves
      with initial, predominantly negative deflection. The most useful diagnostic
      findings were in lead aVF, where a Q wave was present in 10 of 35 patients in the
      MI group compared with only 4 of 131 patients in the normal group (p <0.00001).
      Diagnostic T-wave inversion was noted in 23 of 35 patients in the MI group
      compared with 8 of 131 patients in the normal group (p <0.00001). The presence in
      lead aVF of either a diagnostic Q-wave or T-wave inversion was seen in 30 of 35
      patients with inferior MI (sensitivity of 86%) compared with only 12 of 131
      patients with uncomplicated LBBB (specificity 91%). Thus, these criteria are
      potentially useful for the diagnosis of inferior MI in patients with LBBB.

PMID- 9024730
TI  - Frequency and distribution of atherosclerotic plaques in the thoracic aorta as
      determined by transesophageal echocardiography in patients with coronary artery
      disease.
AB  - The frequency, distribution, and severity of thoracic aortic plaques were
      evaluated by transesophageal echocardiography in 152 consecutive patients
      undergoing coronary arteriography. Coronary artery disease (CAD) was defined as >
      or = 50% stenosis of > or = 1 major branch. Atherosclerotic plaques were detected
      in the aorta in 90 of the 97 patients (93%) with CAD, but in only 12 of the 55
      patients (22%) with normal coronary arteries. Atherosclerotic plaques in patients
      with CAD were found predominantly in the descending aorta (in 93%) and in the
      aortic arch (in 80%), whereas the ascending aorta was the least involved (in
      37%). In the descending aorta, 58% of the plaques were complex (>3 mm thick,
      ulcerated, mobile, or calcified), and in the aortic arch, 40% of the plaques were
      so classified. Complex plaques were not found in the ascending aorta. The
      presence of an atherosclerotic plaque in the descending aorta had a sensitivity
      and a specificity for the prediction of CAD of 93% and 78%, respectively. In the
      ascending aorta, the sensitivity was lower (37%) but the specificity was higher
      (100%). The sensitivity of aortic plaques for the prediction of CAD was high in
      all age groups. Its specificity in subjects >63 years was lower than in younger
      subjects: 64% versus 90%, respectively. Multivariate logistic regression analysis
      showed that aortic plaques were a stronger predictor of CAD than were
      conventional risk factors.

PMID- 9024731
TI  - N-acetylcysteine attenuates nitroglycerin tolerance in patients with angina
      pectoris and normal left ventricular function.
AB  - The aim of this study was to assess whether N-acetylcysteine (NAC) is able to
      prevent tolerance to a 48-hour infusion of nitroglycerin (NTG) in the setting of
      normal left ventricular function. In 16 patients, the hemodynamic response to 0.8
      mg sublingual (s.l.) NTG was assessed by measuring mean arterial, pulmonary
      artery, pulmonary capillary wedge and right atrial pressures, cardiac output, and
      calculation of the systemic and pulmonary vascular resistances. The parameters
      were obtained at baseline and 1 to 10 minutes after the s.l. NTG application (day
      1). NTG was started at 1.5 microg/kg/min; concomitantly, a bolus of 2,000 mg of
      NAC was administered, followed by an infusion of 5 mg/kg/hour. Both infusions
      were continued for 48 hours, and the hemodynamic study was repeated (day 3). The
      same measurements were obtained in a matched control group of 15 patients with
      NTG infusion alone. Plasma renin activity, aldosterone, and norepinephrine were
      measured before and after the infusion period. The first s.l. NTG infusion (day
      1) caused a significant decrease in mean arterial (p <0.01), pulmonary artery (p
      <0.001), and right atrial pressures (p <0.001), and in systemic (p <0.01) and
      pulmonary vascular resistances (p <0.001) in both groups. After the 48-hour
      infusion (day 3), there was a total loss of nitrate-mediated vasodilation
      (pressure values and vascular resistances day 3 > day 1) in 5 of 16 patients (NAC
      nonresponders), whereas in the other 11 of 16 patients (NAC responders), there
      was significant vasodilation throughout the infusion period. Tolerance had
      developed in 14 of 15 patients with NTG infusion alone. The same difference
      (responder vs nonresponder vs NTG alone) held true regarding the response to the
      second s.l. NTG infusion after 48 hours. The neurohormonal counter-regulation and
      intravascular volume expansion (increase in plasma renin activity, p <0.001, and
      norepinephrine, p <0.05; decrease in aldosterone, p <0.01) did not differ between
      responders and nonresponders. We conclude that NAC attenuates tolerance
      development to a continuous NTG infusion in a specific patient subgroup and that
      this occurs despite the same amount of neurohormonal counter-regulation and
      intravascular volume expansion compared with patients with tolerance development.

PMID- 9024732
TI  - Long-term effects of water-soluble dietary fiber in the management of
      hypercholesterolemia in healthy men and women.
AB  - Fifty-one healthy, moderately hypercholesterolemic men and women consuming their
      usual fat-modified diets completed a 6-month, randomized, double-blind, placebo
      controlled, parallel comparison of 15 g/day supplemental water-soluble dietary
      fiber (WSDF; a mixture of psyllium, pectin, guar gum, and locust bean gum) and an
      inactive WSDF control (acacia gum). Compliance with the treatments was > 95%,
      adverse effects were minimal, and body weights remained constant. The WSDF
      mixture yielded 6.4% and 10.5% reductions in mean plasma total and low-density
      lipoprotein cholesterol concentrations, respectively, after 8 weeks, which were
      sustained at 16 and 24 weeks. Mean plasma high-density lipoprotein cholesterol
      and triglyceride concentrations were unchanged. No significant changes in mean
      plasma lipid or lipoprotein concentrations were observed in the control group.
      These data demonstrate that a WSDF approach to cholesterol management is
      effective as an adjunct to a fat-modified diet in healthy, moderately
      hypercholesterolemic men and women.

PMID- 9024734
TI  - Impact of the Food and Drug Administration approval of flecainide and encainide
      on coronary artery disease mortality: putting "Deadly Medicine" to the test.
AB  - In his book Deadly Medicine and on television, Thomas Moore impugns the process
      of antiarrhythmic drug approval in the 1980s, alleging that the new generation of
      drugs had flooded the marketplace and had caused deaths in numbers comparable to
      lives lost during war. To assess these important public health allegations, we
      evaluated annual coronary artery disease death rates in relation to
      antiarrhythmic drug sales (2 independent marketing surveys). Predicted mortality
      rates were modeled using linear regression analysis for 1982 through 1991.
      Deviations from predicted linearity were sought in relation to rising and falling
      class IC and overall class I antiarrhythmic drug use. Flecainide came to market
      in 1986 and encainide in 1987. Combined class IC sales peaked in 1987 and 1988
      (maximum market penetration, 20%, first quarter 1989). Results of the Cardiac
      Arrhythmia Suppression Trial (CAST) were disclosed in April 1989. Overall annual
      class I antiarrhythmic prescription sales actually fell slightly (-3% to -4%/yr)
      in the 2 years before CAST and then more abruptly (- 12%) in the year after CAST
      (1990). Sales of class IC drugs fell dramatically after CAST (by 75%). Coronary
      death rates (age adjusted) fell in a linear fashion during the decade of 1982
      through 1991. No deviation from predicted rates was observed during the
      introduction, rise, and fall in class IC (and other class I) sales: rates were
      126/100,000 in 1985 (before flecainide), 114 and 110 in 1987 and 1988 (maximum
      sales), and 103 in 1990 (after CAST). Deviations in death rates in the postulated
      range of 6,000 to 25,000 per year were shown to be excluded easily by the 95%
      confidence intervals about the predicted rates. Entry of new antiarrhythmic drugs
      in the 1980s did not lead to overall market expansion and had no adverse impact
      on coronary artery disease death rates, which fell progressively. Thus, the
      allegations in Deadly Medicine could not be confirmed.

PMID- 9024733
TI  - The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day.
AB  - The hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin is the most
      effective of the currently approved hypolipidemic drugs and has been shown to
      reduce mortality and coronary morbidity in patients with coronary artery disease.
      For these patients the United States National Cholesterol Education Program
      advocates reducing low-density lipoprotein (LDL) cholesterol to <100 mg/dl.
      However, in some patients this cannot be achieved using monotherapy with
      simvastatin 40 mg/day, the current maximal recommended dose. To evaluate the
      effectiveness of extending the dosage range, 156 subjects with LDL cholesterol
      >160 mg/dl and triglycerides (TG) <350 mg/dl were randomized to simvastatin at
      doses of 40, 80, and 160 mg/day in a 26 week, double-blind, 3-period, complete
      block crossover study. Each active treatment period was 6 weeks in duration with
      intervening 2 week washout periods. Median reductions from baseline in LDL
      cholesterol were 41%, 47%, and 53% in the 40-, 80-, and 160-mg groups,
      respectively. The corresponding reductions in plasma TG were 21%, 23%, and 33%.
      High-density lipoprotein (HDL) cholesterol increased by 6% to 8% in each group.
      One patient (0.7%) taking 160 mg developed myopathy; 1 patient (0.7%) taking 80
      mg, and 3 (2.1%) taking 160 mg had transaminase elevations > 3 times the upper
      limit of normal. No new or unexpected adverse effects were observed. We conclude
      that simvastatin at doses of 80 and 160 mg/day provides additional efficacy with
      a low short-term incidence of adverse effects; our results support the continued
      investigation of simvastatin at these doses.

PMID- 9024735
TI  - Factors associated with elevated impedance with a nonthoracotomy defibrillation
      lead system.
AB  - Peak current flow across the heart determines the success of defibrillation and
      is inversely dependent on impedance between defibrillation electrodes. Factors
      associated with elevated impedance in patients with implantable defibrillators
      using nonthoracotomy lead systems have not been well described. Clinical and
      echocardiographically derived variables were analyzed in 41 patients in whom
      implantation of a nonthoracotomy lead system was attempted. Lead impedance was
      measured at end-expiration with 5-J monophasic shocks. Successful defibrillation
      with or without addition of a subcutaneous patch with < or = 20 J with a
      monophasic waveform was required for nonthoracotomy lead placement. Patients were
      divided into 2 groups based on impedance: low (< or = 47 ohms, n = 30) and high
      (>47 ohms, n = 11). Twenty-four patients had successful defibrillator
      implantation using a transvenous lead alone, 13 required placement of a
      subcutaneous patch, and 4 required epicardial patch placement. The mean left
      ventricular end-diastolic and end-systolic volumes were significantly smaller (p
      = 0.01 for both) in patients in the low- versus high-impedance groups and were
      significantly correlated with impedance (r = 0.44, p <0.005 for both). Impedance
      was not significantly different between patients with successful defibrillation
      using a transvenous lead alone compared with those who required either
      subcutaneous or epicardial patches. Thus, impedance using a nonthoracotomy lead
      system with monophasic shocks is significantly correlated with both end-systolic
      and end-diastolic volumes, but elevated impedance does not predict increased
      defibrillation energy requirements.

PMID- 9024736
TI  - Efficacy, safety, and determinants of conversion of atrial fibrillation and
      flutter with oral amiodarone.
AB  - Amiodarone is effective for long-term maintenance of sinus rhythm after
      electrical cardioversion of refractory atrial fibrillation or flutter. To examine
      its efficacy and safety for pharmacologic conversion of these arrhythmias, we
      studied 129 patients with refractory atrial fibrillation or flutter who had
      failed previous intensive conventional antiarrhythmic treatment. In anticipation
      of electrical cardioversion, patients were loaded with amiodarone, 600 mg/day
      during a 4-week period. The main outcome measure was pharmacologic conversion
      during this period. During the loading period, 23 patients (18%) converted to
      sinus rhythm. When analyzed in a multivariate model, conversion was related to
      desethylamiodarone plasma level (p = 0.0006), arrhythmia duration (p = 0.04),
      left atrial area (p = 0.02), and concomitant treatment with verapamil (p = 0.01).
      During ongoing atrial fibrillation after loading, the ventricular rate decreased
      from 100 +/- 25 to 87 +/- 27 beats/ min (p <0.001). Amiodarone appeared to be
      safe and did not have to be discontinued because of intolerable side effects.
      Thus, amiodarone loading is safe and is still able to convert refractory atrial
      fibrillation or flutter. Conversion is related to increased desethylamiodarone
      plasma levels and concomitant treatment with verapamil. Because prolonged loading
      may increase desethylamiodarone plasma concentrations, this may enhance efficacy
      and obviate the need for electrical cardioversion.

PMID- 9024737
TI  - A comprehensive management system for heart failure improves clinical outcomes
      and reduces medical resource utilization.
AB  - The effectiveness of heart failure management in clinical practice is limited by
      physicians' suboptimal utilization of effective medications, patients' poor
      adherence to dietary sodium limitation and optimal drug therapy, and the lack of
      systematic monitoring of patients after hospitalization. The present study
      evaluated the feasibility and safety of MULTIFIT, a physician-supervised, nurse
      mediated, home-based system for heart failure management that implements
      consensus guidelines for pharmacologic and dietary therapy using a nurse manager
      to enhance dietary and pharmacologic adherence and to monitor clinical status by
      frequent telephone contact. Fifty-one patients with the clinical diagnosis of
      heart failure were followed for 138 +/- 44 days. Daily dietary sodium intake fell
      by 38%, from 3,393 to 2,088 mg (p = 0.0001); average daily medication doses
      increased significantly (lisinopril: 17 to 23 mg, p <0.001; hydralazine: 140 to
      252 mg, p = 0.01). Functional status and exercise capacity improved significantly
      (p = 0.01). Compared with the 6 months before enrollment and normalized for
      variable follow-up, the frequency of general medical and cardiology visits
      declined by 23% and 31%, respectively (both p <0.03); emergency room visits for
      heart failure and for all causes declined 67% and 53%, respectively (both p
      <0.001). Hospitalization rates for heart failure and for all causes declined 87%
      and 74%, respectively (p = 0.001), compared with the year before enrollment. The
      MULTIFIT system enhanced the effectiveness of pharmacologic and dietary therapy
      for heart failure in clinical practice, improving clinical outcomes and reducing
      medical resource utilization.

PMID- 9024738
TI  - Putting low-density lipoproteins at center stage in atherogenesis.
AB  - This article argues that major risk factors such as diabetes or hypertension
      increase the risk of vascular disease principally by amplifying the malign
      interactions of low-density lipoprotein (LDL) particles with the arterial wall
      and, consequently, that LDL is the first and foremost factor in the pathogenesis
      of vascular disease. We conclude that marked reduction of the LDL particle number
      should be the cornerstone of therapy in those with vascular disease or in those
      at high risk of vascular disease.

PMID- 9024739
TI  - Prevalence of spinal disc disease among interventional cardiologists.
AB  - A suspected, but undocumented, excess of axial skeletal disease among
      interventional cardiologists (possibly a consequence of lead apron use) was
      investigated by comparing questionnaire responses from cardiologists, orthopedic
      surgeons, and rheumatologists (n = 714). Cardiologists reported more neck and
      back pain, more subsequent time lost from work, and a higher incidence of
      cervical disc herniations, as well as multiple level disc disease (all p <0.01):
      "interventionalist's disc disease" is a confirmed entity.

PMID- 9024740
TI  - Publications concerning costs of various cardiovascular procedures and drugs.
AB  - The following is a compendium of economic articles considered to be the most
      important and informative in the field of mechanical and pharmacologic treatment
      of coronary artery disease. This reference list was compiled from the literature
      and the MEDLINE database and includes citations before 1996.

PMID- 9024741
TI  - Changes in hemostatic function at times of cyclic variation in occupational
      stress.
AB  - In this study we demonstrated, in the same healthy subjects, a significant
      elevation in coagulation factors VII and VIII, fibrinogen, thrombocyte count, and
      thrombin and adenosine diphosphate-induced platelet aggregation during a period
      of increased workload compared with a calm work period. These findings may add to
      the understanding of the mechanism that links mental stress to coronary disease.

PMID- 9024742
TI  - Blockade of K(ATP) channels with glibenclamide does not abolish preconditioning
      during demand ischemia.
AB  - The role of adenosine triphosphate-sensitive potassium channels in the adaptive
      response to demand ischemia was tested in 22 patients treated with placebo or
      glibenclamide before sequential exercise testing or atrial pacing. Glibenclamide
      did not affect the improvement in signs of ischemia in both protocols, indicating
      that opening of these channels is not a mechanism of this adaptive response in
      humans.

PMID- 9024743
TI  - T-wave alterations at the onset of wall motion abnormalities during dobutamine
      echocardiographic stress test.
AB  - At the onset of wall motion alterations during dobutamine echocardiographic
      stress testing, a steeper increase in the overall T-wave amplitude in the
      precordial leads was observed in 17 patients with baseline normal wall motion,
      electrocardiogram, and critical coronary stenoses compared with 11 control
      subjects. Eleven patients with increasing T-wave amplitude had localized apical
      dyssynergy, whereas 6 patients with downward displacement of the ST segment had
      widespread wall motion alterations also located at the basal and midsegments.

PMID- 9024744
TI  - Usefulness of coronary stenting for cardiogenic shock.
AB  - Coronary stenting was performed in 15 selected patients with cardiogenic shock,
      with favorable clinical and angiographic outcomes. This experience suggests that
      coronary stenting may play an important adjunctive role in the management of
      cardiogenic shock and may improve outcome beyond that achieved with balloon
      angioplasty alone.

PMID- 9024745
TI  - Effect of fluvastatin on lipids and fibrinolysis in coronary artery disease.
AB  - This randomized, double-blind, placebo-controlled study shows that 20-week
      fluvastatin treatment induces beneficial changes in the lipid panel and a shift
      in the fibrinolytic pathway toward activation through a decrease in tissue
      plasminogen activator antigen. Fluvastatin treatment causes no variation in
      lipoprotein(a) circulating levels.

PMID- 9024746
TI  - Estrogen replacement therapy and exercise performance in postmenopausal women
      with coronary artery disease.
AB  - We treated 10 postmenopausal women with stable angina, positive exercise test,
      and documented coronary artery disease with oral conjugated equine estrogen
      (0.625 mg/day of Premarin) or placebo for 4 weeks, in random order, with
      crossover after a 4-week washout period. Exercise tests, performed after each
      treatment period while the patients were taking their usual antianginal drugs
      showed no differences; thus, short-term estrogen does not improve exercise
      induced ischemia compared with placebo.

PMID- 9024747
TI  - Impact of plaque burden on compensatory enlargement of coronary arteries in
      cardiac allograft vasculopathy. Working Group on Cardiac Allograft Vasculopathy.
AB  - Using intravascular ultrasound, we demonstrated plaque-induced compensatory
      enlargement of coronary arteries in cardiac allograft vasculopathy. Besides
      intimal hyperplasia, adaptive remodeling processes of vessel and luminal geometry
      have physiologic and prognostic importance.

PMID- 9024748
TI  - Effectiveness of sotalol for atrial flutter in children after surgery for
      congenital heart disease.
AB  - This study describes the efficacy of oral sotalol in the treatment and prevention
      of atrial flutter in children after surgery for congenital heart disease. In 11
      of 13 children (85%), conversion to sinus rhythm was achieved, and in 8 of 11
      within 24 hours.

PMID- 9024749
TI  - Intravenous clofilium for conversion of atrial fibrillation.
AB  - Clofilium was administered to 14 patients with mainly chronic atrial fibrillation
      in a pilot study. QTc prolongation was observed, and 2 patients had conversion to
      sinus rhythm after drug infusion.

PMID- 9024750
TI  - Relation between amiodarone and desethylamiodarone plasma concentrations and
      ventricular defibrillation energy requirements.
AB  - The main finding of this prospective, controlled study is that amiodarone and
      desethylamiodarone plasma concentrations < 1 mg/L are associated with a 23%
      increase in the acute defibrillation energy requirement and with a 31% increase
      in the requirement for a subcutaneous patch or array. The defibrillation energy
      requirement does not correlate with the plasma concentrations of amiodarone,
      desethylamiodarone, amiodarone plus desethylamiodarone, or with the duration or
      daily dosage of amiodarone therapy.

PMID- 9024751
TI  - Paradoxical failure of QT prolongation during cardioinhibitory neurocardiogenic
      syncope.
AB  - QT modulation was explored in 31 patients with cardioinhibitory neurocardiogenic
      syncope. Despite a marked in increase in RR intervals, the QT interval remained
      stable.

PMID- 9024752
TI  - Usefulness of echocardiography in detecting left ventricular dysfunction in
      population-based studies (The Rotterdam Study).
AB  - In a population-based study, the routine 12-lead electrocardiogram was found to
      have a high negative predictive value for detecting left ventricular (LV)
      systolic dysfunction. Withholding echocardiography in persons without major
      electrocardiographic abnormalities, however, would result in a considerable
      underestimation of LV systolic dysfunction (sensitivity only 54%); thus,
      echocardiography remains an essential tool for detecting LV systolic dysfunction
      in population-based studies.

PMID- 9024753
TI  - Acute reversibility of pulmonary hypertension predicts neither long-term
      hemodynamic response nor outcome in patients awaiting heart transplantation.
AB  - For transplant wait-list patients with end-stage congestive heart failure,
      reversibility of pulmonary hypertension tested with acute administration of
      vasodilators is a prerequisite to listing for transplantation. We have shown that
      the magnitude of the initial pulmonary vasodilatory response to nitroprusside
      predicts neither the extent of the long-term hemodynamic response nor the
      subsequent need for transplantation versus clinical improvement and removal from
      transplant consideration.

PMID- 9024754
TI  - Effects of hemodialysis on left ventricular diastolic filling.
AB  - Diastolic Doppler filling parameters were measured before and after hemodialyses,
      performed once with and once without fluid removal. Changes occurred only with
      fluid removal and correlated with weight loss, indicating that they are the
      result of reduction in preload.

PMID- 9024755
TI  - Categorization of abnormal left ventricular function: comparison between
      radionuclide angiographic and echocardiographic technique in postinfarction
      patients.
AB  - In postinfarction patients, only biplane echocardiographic evaluation of left
      ventricular ejection fraction (EF) accurately predicts radionuclide EF > or
      <0.35, 0.40, and 0.45. A wall motion scoring system that does not account for
      hyperkinesia of healthy myocardium may be used to discriminate between
      radionuclide EF > or <0.40 or 0.45, but lacks accuracy for 0.35.

PMID- 9024756
TI  - Cervical aortic arch with aneurysm formation.
AB  - Two pediatric cases of cervical aortic arch with aneurysm formation are reported.
      Only female patients with cervical aortic arch have developed aneurysms, which
      may influence risk counseling of such patients.

PMID- 9024776
TI  - Differential response of mesoderm- and neural crest-derived smooth muscle to TGF
      beta1: regulation of c-myb and alpha1 (I) procollagen genes.
AB  - Previously, we demonstrated that avian vascular smooth muscle cells (VSMC)
      derived from embryonic abdominal and thoracic aorta grow differently in the
      presence of transforming growth factor beta (TGF-beta1) and platelet-derived
      growth factor (PDGF-BB) (Wrenn et al., In Vitro Cell. Dev. Biol. 29, 73-78,
      1992). The thoracic VSMC (N-VSMC) are derived from neural crest, and therefore
      differentiate from ectoderm; the abdominal VSMC (M-VSMC) are derived from
      mesoderm. The present study was designed to identify factors that mediate the
      differential responses of the VSMC to TGF-beta1. We found that TGF-beta1
      increased DNA synthesis by approximately sevenfold in N-VSMC. Levels of both
      alpha1 (I) procollagen and c-myb mRNAs were markedly induced in N-VSMC treated
      with TGF-beta1. Chimeric plasmids containing up to 3.5 kb of alpha1 (I)
      procollagen 5' flanking DNA were induced to equivalent levels as procollagen mRNA
      in N-VSMC. However, TGF-beta1 increased DNA synthesis by threefold in M-VSMC;
      there was no effect on alpha1 (I) procollagen expression, and c-myb was not
      expressed, as demonstrated by immunohistochemistry staining and RNA analyses.
      Antisense c-myb oligodeoxynucleotides blocked the TGF-beta1 induction of alpha1
      (I) procollagen and the growth of N-VSMC. The increase in DNA synthesis by M- and
      N-VSMC was correlated with the secretion of PDGF-AA, and staurosporine and
      antibodies directed against PDGF-AA suppressed DNA synthesis. Our results
      demonstrate that TGF-beta1 activity and c-myb expression modulate the expression
      of alpha1 (I) collagen and cell proliferation in neural crest-derived smooth
      muscle. The regulation of these events by TGF-beta1 may be important during
      morphogenesis of blood vessels and vascular diseases.

PMID- 9024777
TI  - The protein phosphatase inhibitors okadaic acid and calyculin A induce apoptosis
      in human osteoblastic cells.
AB  - To determine whether protein phosphorylation and dephosphorylation can affect
      apoptosis in osteoblastic cells, we examined the effects of okadaic acid (OA) and
      calyculin A (CA) on cultured human osteoblastic cells Saos-2 and MG63, and mouse
      osteoblastic MC3T3-E1 cells. After reaching confluence, these cells were exposed
      to varying concentrations of OA or CA. OA and CA induced cell death in all three
      cell lines in a dose- and time-dependent manner. Marked nuclear condensation and
      fragmentation of chromatin were also observed in these cells by using the Hoechst
      33342 stain. DNA ladder formation, a hallmark of apoptosis, was detected in Saos
      2 and MG63 cells, but not in MC3T3-E1 cells by treatment of OA or CA. In the Saos
      2 cells, OA- and CA-induced DNA ladder formation was dose-dependent with maximal
      effect at concentrations of 10 and 2 nM, respectively, and was time-dependent
      from 14 to 48 h. DNA ladder formation in response to OA and CA was revealed by
      using conventional ethidium bromide staining of electrophoresed DNA without using
      autoradiography. Beyond the maximal effects at the respective concentrations,
      however, cell death did not indicate DNA laddering, suggesting that phosphatase
      activity may be required for ladder formation. Our results indicate that
      apoptosis in the cultured osteoblastic cells is induced by moderate inhibition of
      PP-1 or PP-2A based on the known selectivity of okadaic acid and of calyculin A.

PMID- 9024778
TI  - The involvement of tissue-type plasminogen activator in parietal endoderm
      outgrowth.
AB  - When F9 stem cells are treated in suspension with retinoic acid, they
      differentiate into embryoid bodies (EBs) consisting of an inner core of
      undifferentiated stem cells surrounded by an outer layer of visceral endoderm
      (VE). When these EBs are plated onto a fibronectin (FN)-coated substrate, VE
      derived parietal endoderm (PE) cells migrate onto the substrate. It has been
      suggested that increased levels of tPA associated with the emerging PE cells may
      help mediate PE outgrowth. We now show that goat anti-human tPA, an anticatalytic
      antibody that crossreacts with mouse tPA, and a panel of serine protease
      inhibitors partially inhibit PE outgrowth. Extracellular matrix (ECM) degradation
      analysis demonstrates that PE cell-mediated degradation of [3H]proline-labeled
      ECM is time- and cell concentration-dependent. A serine protease inhibitor
      reduced the extent of degradation, suggesting that tPA might play a role in PE
      outgrowth by cleaving the ECM. In support of this contention, we demonstrate that
      incubation of purified FN with conditioned medium plus plasminogen results in FN
      proteolysis. The degradation of FN is blocked by either serine protease
      inhibitors or goat anti-human tPA. Our data suggest that enhanced production of
      tPA during PE outgrowth may facilitate the migratory behavior of PE cells by
      mediating the degradation of ECM components such as FN.

PMID- 9024779
TI  - Propagation of mechanically induced intercellular calcium waves via gap junctions
      and ATP receptors in rat liver epithelial cells.
AB  - Mechanical stimulation was used to initiate Ca2+ waves in rat liver epithelial
      cells in order to ascertain the degree to which gap junctional intercellular
      communication (GJIC) is involved in communication of Ca2+ to adjacent cells and
      to assess alternative Ca2+ signaling pathways that may be present between these
      cells. In both WB-F344 cells, which show a high degree of GJIC, and WB-aB1 cells,
      which are GJIC deficient, mechanical stimulation of a single cell induced a Ca2+
      wave which propagated away from the point of stimulation, across cell borders, to
      neighboring cells directly or indirectly in contact with the stimulated cell. In
      addition, the Ca2+ wave was transmitted to nearby isolated cells that exhibited
      no direct or indirect contact with the stimulated cell. Treatment of cells with
      18beta-glycyrrhetinic acid, a compound that has been shown to block GJIC, did not
      significantly affect propagation of the Ca2+ wave. In contrast, treatment with
      suramin, a P2-purinergic receptor inhibitor, significantly reduced both the rate
      and the extent of Ca2+ wave propagation in WB-F344 cells and completely blocked
      its propagation in WB-aB1 cells. Cotreatment with suramin and glycyrrhetinic acid
      was found to completely block the mechanically induced Ca2+ wave in both cell
      lines. These studies indicate that mechanically induced cell injury in rat liver
      epithelial cells initiates signaling through at least two pathways, involving
      intercellular communication via gap junctions and extracellular communication via
      ATP activation of purinergic receptors.

PMID- 9024780
TI  - Reactivation of an inactive human X chromosome introduced into mouse embryonal
      carcinoma cells by microcell fusion with persistent expression of XIST.
AB  - An inactive human X chromosome was introduced by microcell fusion into two mouse
      embryonal carcinoma cell lines, PSA1-TG8 and OTF9-63, each of which has a single
      X chromosome. The donor cell line was a mouse-human somatic cell hybrid, CF150,
      retaining one or more inactive human X chromosome(s) per cell as its only human
      element. Twenty hybrid clones isolated retained EC morphology and contained the
      intact human X chromosome(s) or its truncated derivative(s). Replication banding
      analysis showed that the introduced human X chromosome(s) or its derivative(s)
      replicated synchronously with other mouse chromosomes, suggesting reactivation of
      the human X chromosomal elements after transfer. Reversal of inactivation was
      further confirmed by the expression of five human X-linked genes repressed in
      CF150, although the XIST (X inactive specific transcript) gene continued to be
      active. The level of XIST expression in our hybrid cells was almost identical to
      that of parental CF150 cells. Methylation status of 5' end of the active XIST
      gene varied considerably from almost full methylation to unmethylation in these
      hybrids. Thus, mouse EC cells used in this study were capable of altering
      methylation status of the human XIST gene in a manner lacking consistency and
      unable to repress its transcription. Furthermore, we failed to obtain any
      positive evidence for the occurrence of X chromosome inactivation in
      differentiating monochromosome EC hybrids. Taken together, these findings suggest
      that the human X chromosome inactivation center including the XIST gene is unable
      to function effectively in mouse cells.

PMID- 9024781
TI  - Jun and JNK kinase are activated in thymocytes in response to VM26 and radiation
      but not glucocorticoids.
AB  - In order to establish what role members of the activating protein-1 (AP-1) gene
      families, i.e., c-fos, c-jun, junB, and junD, play in thymic apoptosis, we have
      analyzed changes in their expression in response to three different agents: a
      glucocorticoid analog dexamethasone, an inhibitor of topoisomerase II teniposide
      VM26, and gamma radiation. All three agents induced thymic death at a similar
      rate and with the same morphological and biochemical features. There was a rapid
      and transient increase in the steady-state mRNA level of junB and c-fos genes in
      all treatments, including control cultures, reminiscent rather of cellular stress
      response to the environmental changes than to the apoptotic stimuli. On the other
      hand, treatments with the DNA-damaging agents, VM26 and gamma radiation, resulted
      in superinduction of the c-jun mRNA and in the activation of the stress response
      signaling pathway of c-Jun N-terminal kinase. Gene transcription ceased
      completely in cells with fragmented DNA and the down-regulation of genes such as
      junD and tubulin was reflective of the thymocytes' commitment to apoptosis. The
      DNA-binding activities of the serum response factors, cyclic AMP response element
      binding proteins, and AP-1 factors, indicative of their transcriptional
      competence, were compromised shortly after induction of apoptosis regardless of
      the agent employed, consistent with previously reported enhancement in cellular
      proteolysis which is an essential component of the apoptotic cell death.

PMID- 9024782
TI  - Integrin-mediated tyrosine phosphorylation and redistribution of paxillin during
      neuronal adhesion.
AB  - Integrins are important receptors for neuronal adhesion to laminin, which is one
      of the best promoters of neurite outgrowth. The present study was carried out to
      understand some of the intracellular mechanisms which allow integrin-mediated
      neurite extension on laminin. In chicken retinal neurons, integrin-mediated
      adhesion to laminin and antibody-induced integrin clustering caused an increase
      in tyrosine phosphorylation of paxillin and focal adhesion kinase. The kinetics
      of phosphorylation and dephosphorylation of these proteins were different in
      neurons plated on laminin, compared to neurons in which the receptors were
      clustered with anti-integrin antibodies. Analysis of sucrose velocity gradients
      could not show any association of paxillin and focal adhesion kinase with the
      integrin receptors. On the other hand, by using digitonin and milder extraction
      conditions, we found an enrichment of the tyrosine-phosphorylated polypeptides in
      the cytoskeletal, digitonin-insoluble fraction. Furthermore, neuronal adhesion
      induced a dramatic increase in the fraction of tyrosine-phosphorylated paxillin
      recovered with the digitonin-insoluble fraction, suggesting redistribution of
      this protein following adhesion of neurons to laminin. Localization studies on
      the detergent-insoluble fraction showed codistribution of both paxillin and focal
      adhesion kinase with integrins. We also found that paxillin tyrosine
      phosphorylation, but not paxillin expression, is developmentally regulated in the
      retina. Our results show that integrin-mediated neuronal adhesion leads to the
      accumulation of a pool of highly phosphorylated proteins at adhesion sites. There
      they may be responsible for the reorganization of the cytoskeleton, which
      underlies the process of neurite extension.

PMID- 9024783
TI  - A novel technique for culture of human dermal microvascular endothelial cells
      under either serum-free or serum-supplemented conditions: isolation by panning
      and stimulation with vascular endothelial growth factor.
AB  - Several physiological and pathophysiological events involving vascular
      endothelium occur at the microvascular level. Studies on human microvasculature
      require homogenous primary cultures of microvascular endothelial cells. However,
      procedures available for isolating and culturing human dermal microvascular cells
      (HDMEC) result in significant contamination with fibroblasts. To eliminate
      contamination with fibroblasts or other cells, we developed a procedure to
      isolate HDMEC from neonatal human foreskin by panning the cells using EN4, an
      anti-endothelial cell monoclonal antibody. Panned cells uniformly expressed von
      Willebrand factor and CD36, confirming their microvascular endothelial
      characteristics, whereas cells cultured without panning showed a significant
      degree of contamination with fibroblasts. In the presence of vascular endothelial
      growth factor (VEGF), HDMEC could be cultured under serum-free conditions. VEGF
      stimulated the growth of HDMEC in a dose-dependent manner in serum-free medium or
      in media supplemented with either human serum or newborn calf serum. Since
      differences exist between large vessel endothelial cells and microvascular
      endothelial cells, we compared the response to VEGF stimulation of HDMEC with
      human umbilical vein endothelial cells (HUVEC). The dose response of the two cell
      types to VEGF was different. This effect of VEGF on endothelial cells may be
      mediated by the VEGF receptor kdr, since mRNA for kdr was detected using RT-PCR
      in both HDMEC and HUVEC. The procedure described in this study will make possible
      the culture of highly enriched HDMEC without contamination with fibroblasts and
      facilitate studies with these cells under defined assay conditions in a serum
      free environment.

PMID- 9024784
TI  - Constitutive expression of human ribosomal protein L7 arrests the cell cycle in
      G1 and induces apoptosis in Jurkat T-lymphoma cells.
AB  - Protein L7 is involved in translational control in eucaryotic cells as indicated
      by its association with ribosomes, its capability to inhibit specifically the
      cell-free translation of distinct mRNAs, and its interference with the synthesis
      of two major nucleus-associated proteins in L7 cDNA-transfected Jurkat T-lymphoma
      cells [F. Neumann et al. (1995) Nucleic Acids Res. 23, 195]. In this report we
      show that the constitutive expression of protein L7 in Jurkat cells leads to an
      arrest in G1 of the cell cycle and induces apoptosis as a consequence of cell-to
      cell contact. Treatment of the L7 transfectants with the inhibitor of translation
      cycloheximide, at doses which do not affect untransfected cells, enhances their
      sensitivity to the induction of apoptosis. These results suggest that L7 can
      interfere with the translation of proteins which control cell cycle progression
      and/or the initiation of the apoptotic pathways.

PMID- 9024785
TI  - 2-Aminopurine induces spindle cell morphology in MM14 myoblasts in the absence of
      differentiation signals.
AB  - MM14 murine myoblast cells remain in an undifferentiated and proliferative state
      if they are maintained in the continuous presence of basic fibroblast growth
      factor (FGF-2) and serum factors, but terminally differentiate into myocytes and
      myotubes if deprived of FGF-2 during G1 of the cell cycle. We find that 2
      aminopurine (2-AP) induces a reversible, rapid, and profound alteration in the
      morphology of proliferating MM14 cells to a polarized shape which is similar to
      that observed during normally induced differentiation. This change requires
      neither a differentiation signal nor de novo protein synthesis. In contrast, we
      do not observe a morphological change in response to 2-AP in nonmyogenic cell
      lines. The morphological alteration of MM14 cells in response to 2-AP requires
      reorganization of the microtubule and actin cytoskeletons, in common with changes
      during normal differentiation. Additionally, we show that cytoskeletal
      rearrangements that occur during both normal differentiation and in response to 2
      AP require the activity of the small GTPase Rho. Differentiation defective MM14
      cells (DD-1 cells), which lack MyoD, also undergo a profound morphological
      alteration in the presence of 2-AP. These results indicate that morphological
      changes consistent with myoblast differentiation are regulated by a pathway
      independent of MyoD transcriptional control.

PMID- 9024786
TI  - Preferential adhesion to and survival on patterned laminin organizes myogenesis
      in vitro.
AB  - We have examined a potential role for differential adhesiveness in muscle
      development using an in vitro model which employed the culture of myoblasts and
      myotubes, (conditionally immortal myogenic cells, H2k(b)-tsA58), on
      micropatterned surfaces. These surfaces are made up of multiple alternating
      tracks of hydrophobic organosilane-treated glass and untreated glass (track width
      ranging from 5 to 100 microm). We found that myoblasts were aligned on patterns
      in the presence of serum, by adhering to the tracks of untreated glass, which had
      preferentially adsorbed serum attachment factors. However, as serum attachment
      factors are not sufficient for maintenance of adhesion of mature myotubes, we
      determined whether precoating patterns with laminin, which maintains adhesion,
      could still provide a differential adhesive cue. Laminin preferentially adsorbs
      to the hydrophobic regions resulting in alternating tracks that have adsorbed
      laminin or serum attachment factors. Myoblasts were less well aligned on these
      patterns as they could adhere both to the untreated glass and to laminin on the
      previously hydrophobic tracks, but did show a preference for laminin. However,
      cell alignment increased upon differentiation into myotubes and continued to
      increase as the myotubes matured. We found that the alignment of myoblasts and
      myotubes on patterns increased as track width increased. In addition, adhesion to
      laminin was required for long term survival of the myotubes. Myotubes that had
      formed on nonlaminin surfaces began to detach after 2 days of differentiation.
      Although we found that myoblasts preferentially clustered on laminin tracks, this
      arrangement did not influence the diameter of the myotubes formed, upon
      differentiation. Instead, the number of myotubes per track increased with track
      width, while the myotube diameter remained constant. This uniformity of myotube
      diameter suggests that a mechanism exists which restricts the ability of
      myoblasts to undergo lateral fusion. Overall, these findings suggest that
      differential adhesiveness could be an important mechanism for formation and
      survival of myotubes, and by using these patterns we have demonstrated a
      mechanism controlling the formation of linear myotubes by restricting the
      geometry of cell-cell adhesion.

PMID- 9024787
TI  - The IGF-I receptor in mitogenesis and transformation of mouse embryo cells: role
      of receptor number.
AB  - The type 1 receptor for insulin-like growth factors (IGF-IR) plays an important
      role in the growth and transformation of several types of cells. We have
      investigated the role of IGF-IR number in IGF-I-mediated mitogenesis and
      transformation of mouse embryo fibroblasts. We have used R- cells (3T3-like cells
      originating from mouse embryos with a targeted disruption of the IGF-IR genes)
      transfected with a plasmid expressing the human IGF-IR cDNA to generate clones
      with receptor numbers ranging from zero to 10(6) receptors per cell. In this
      model, between 15,000 and 22,000 receptors per cell are sufficient to render
      mouse embryo cells competent to grow in serum-free medium supplemented solely
      with IGF-I. For growth in soft agar, 30,000 receptors per cell seem to be the
      minimum requirement. These experiments indicate that a small increment in the
      number of receptors per cell, well within the physiological range, can modulate
      the mitogenic and transforming activities of the IGF-IR in 3T3-like cells.

PMID- 9024788
TI  - Import of plasmid DNA into the nucleus is sequence specific.
AB  - Nuclear import of plasmid DNA in nondividing cells is a process essential to the
      success of numerous viral life cycles, gene therapy protocols, and gene
      expression experiments. Here, intact protein-free SV40 DNA was cytoplasmically
      injected into cells and its subcellular localization was followed by in situ
      hybridization. SV40 DNA localized to the nucleus consistent with a mechanism of
      transport through the nuclear pore complex (NPC): import was inhibited by the
      addition of the NPC-inhibitory agents wheat germ agglutinin and an anti
      nucleoporin antibody as well as by energy depletion. DNA transport appeared to be
      a multistep process with the DNA accumulating at the nuclear periphery before its
      import. Most importantly, nuclear import was sequence specific: a region of SV40
      DNA containing the origin of replication and the early and late promoters
      supported import, whereas bacterial sequences alone and other SV40-derived
      sequences did not. The majority of the imported DNA colocalized with the SC-35
      splicing complex antigen, suggesting that the intranuclear DNA localizes to areas
      of transcription or message processing. This link to transcription was
      strengthened by the finding that inhibition of transcription blocked DNA import
      but not protein nuclear import. Taken together, these results support a model in
      which plasmid DNA nuclear import occurs by a mechanism similar to that used by
      nuclear localization signal-containing proteins but is also dependent on
      transcription.

PMID- 9024789
TI  - The timing and magnitude of Ca2+ signaling by CD32 depends on its redistribution
      on the cell surface.
AB  - Ca2+ signaling was correlated with microaggregation and capping of CD32 molecules
      on the myeloid cell line, U937. The cytosolic free Ca2+ signal was related to the
      extent of CD32 cross-linking and arose asymmetrically within individual cells.
      Both the magnitude and the delay before Ca2+ signaling via CD32 on U937 cells was
      dependent on the extent of CD32 cross-linking. The delay time was extended in
      cells in which lateral diffusion in the membrane was reduced by covalently cross
      linking of surface proteins. Under these conditions, capping but not surface
      microaggregation of CD32 molecules was prevented. The delay time before Ca2+
      signaling but not the magnitude was also affected. At a higher density of
      covalent cross-linking of surface proteins, the magnitude of the Ca2+ signal by
      CD32 was also reduced and could be completely inhibited. This evidence therefore
      shows that the formation of a CD32 "cap" was not required for Ca2+ signaling by
      this route. However, the signaling delay time was a consequence of lateral
      diffusion of CD32 molecules in the membrane to form signaling-competent
      microaggregates, and the redistribution of CD32 molecules on the cell surface was
      required for Ca2+ signal generation.

PMID- 9024790
TI  - Characterization and physiological importance of a novel cell cycle regulated
      protein kinase in Xenopus laevis oocytes that phosphorylates cyclin B2.
AB  - We have partially purified a specific cyclin B2 kinase (cyk) from prophase
      oocytes of Xenopus laevis after an ATP-gamma-S activation step. Phosphopeptide
      analysis identified Ser53 as the major in vitro phosphorylation site for cyk in
      cyclin B2. Using a synthetic peptide derived from cyclin B2 encompassing Ser53
      (cyktide) as a substrate, cyk was shown to be activated during progesterone
      induced maturation, with a peak of activity between 40 and 50% maturation. A
      sustained high cyk activity was observed in oscillating egg extracts.
      Microinjection of cyk-phosphorylated cyclin B2 into prophase oocytes accelerated
      progesterone-induced maturation by about 2 h, indicating that cyclin B2 is a
      relevant substrate for cyk and that the function of cyk is situated upstream of
      cdc2-cyclin B activation. Microinjection of cyk-phosphorylated cyktide or a
      combination of cyk and cyclin B1 into G2 fibroblasts induced significant changes
      in cell morphology, reminiscent of a premature prophase-like phenotype.
      Similarly, addition of cyk-phosphorylated cyktide in cyclin B1-dependent
      interphase extracts resulted in histone H1 kinase activation.

PMID- 9024791
TI  - Association of nuclear matrix proteins with granular and threaded nuclear bodies
      in cell lines undergoing apoptosis.
AB  - The granules which appear in the nucleolar area in apoptotic HL-60 cells after
      camptothecin administration (Zweyer et al., Exp. Cell Res. 221,27-40, 1995) were
      detected also in several other cell lines induced to undergo apoptosis by
      different stimuli, such as MOLT-4 treated with staurosporine, K-562 incubated
      with actinomycin D, P-815 exposed to temperature causing heat shock, Jurkat cells
      treated with EGTA, U-937 growing in the presence of cycloheximide and tumor
      necrosis factor-alpha, and HeLa cells treated with etoposide. Using
      immunoelectron microscopy techniques, we demonstrate that, besides the already
      described nuclear matrix proteins p125 and p160, these granules contain other
      nucleoskeletal polypeptides such as proliferating cell nuclear antigen, a
      component of ribonucleoprotein particles, a 105-kDa constituent of nuclear
      spliceosomes, and the 240-kDa nuclear mitotic apparatus-associated protein
      referred to as NuMA. Moreover, we also found in the granules SAF-A/hn-RNP-U and
      SATB1 proteins, two polypeptides that have been reported to bind scaffold
      associated regions DNA sequences in vitro, thus mediating the formation of looped
      DNA structures in vivo. Fibrillarin and coilin are not present in these granules
      or the PML protein. Thus, the granules seen during the apoptotic process
      apparently are different from coiled bodies or other types of nuclear bodies.
      Furthermore, these granules do not contain chromatin components such as histones
      and DNA. Last, Western blotting analysis revealed that nuclear matrix proteins
      present in the granules are not proteolytically degraded except for the NuMA
      polypeptide. We propose that these granules might represent aggregates of nuclear
      matrix proteins forming during the apoptotic process. Moreover, since the
      granules are present in several cell lines undergoing apoptosis, they could be
      considered a previously unrecognized morphological hallmark of the apoptotic
      process.

PMID- 9024792
TI  - Hepoxilin-evoked intracellular reorganization of calcium in human neutrophils: a
      confocal microscopy study.
AB  - Hepoxilin A3 has previously been shown to cause a rapid dose-dependent rise in
      intracellular calcium in intact human neutrophils in suspension. Two components
      have been observed, an initial rapid phase of intracellular calcium rise,
      followed by a slow decline to plateau levels that remain above the original
      baseline calcium levels. These changes have been suggested to involve the release
      of calcium from intracellular stores in the ER (initial rapid phase), while the
      slower rate of decline (plateau phase) was presumed to be due to calcium influx
      as it was abolished in zero calcium extracellular medium. The present study used
      confocal microscopy to examine the response to hepoxilin A3 at the subcellular
      level. Our results show that calcium dynamics in response to hepoxilin A3 varies
      in different subcellular compartments within the cell and that hepoxilin A3
      evoked a persistent accumulation of calcium in organelles. The hepoxilin-evoked
      calcium sequestration was eliminated by prior exposure to CCCP, a mitochondrial
      uncoupler. CCCP also eliminated the plateau phase of the calcium response in cell
      suspension, suggesting that this phase was due to mitochondrial accumulation of
      calcium rather than calcium influx. Experiments with DiI-loaded cells, a membrane
      marker, showed that the nuclear calcium was not elevated by hepoxilin addition to
      the cells. These results demonstrate that hepoxilins evoke the release of calcium
      from the ER which is taken up by the mitochondria where it is tightly
      sequestered. These results offer an explanation of observations previously made
      with cell suspensions in which hepoxilin A3 was shown to inhibit the calcium
      mobilizing effects of chemotactic agents.

PMID- 9024794
TI  - Polarity of constitutive and regulated von Willebrand factor secretion by
      transfected MDCK-II cells.
AB  - Von Willebrand factor (vWF), synthesized by endothelial cells, is both rapidly
      secreted by the constitutive pathway and stored in Weibel-Palade bodies.
      Secretion from these organelles occurs upon activation of the protein kinase C
      signal transduction pathway and yields highly multimerized vWF. Highly
      multimerized vWF acts as a more effective adhesive ligand than the lower
      molecular weight forms that are constitutively secreted. We employed the
      extensively characterized polar Madin-Darby Canine Kidney II (MDCK-II) epithelial
      cell line, stably transfected with full-length vWF cDNA or deletion mutants
      thereof, to gain insight in the polarity of vWF secretion by either one of the
      two pathways. Immunofluorescence analysis and metabolic labeling experiments
      revealed that multimeric "wild-type" vWF is stored in MDCK-II cells and released
      upon stimulation with phorbol esters. Furthermore, we show that 62.0 +/- 3.8% of
      constitutively secreted and 83.2 +/- 6.6% of the regulated secreted wild-type vWF
      is encountered at the apical side of the cell. The polarity of the constitutive
      secretion of deletion mutant vWFdelD'D3 is similar to that of constitutively
      secreted wild-type vWF, whereas deletion mutant vWFdelD1D2 displays no polar
      secretion (50.1 +/- 5.7% apical).

PMID- 9024793
TI  - Bone morphogenetic protein-2 inhibits terminal differentiation of myogenic cells
      by suppressing the transcriptional activity of MyoD and myogenin.
AB  - Bone morphogenetic protein (BMP) is a family of cytokines that induce ectopic
      bone formation when implanted into muscular tissues. We reported that BMP-2
      inhibits the terminal differentiation of C2C12 myoblasts and converts them into
      osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E.,
      Takahashi, N., Ikeda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A., and
      Suda, T. (1994) J. Cell Biol. 127, 1755-1766). In the present study, we examined
      the molecular mechanism of the inhibitory effect of BMP-2 on terminal
      differentiation of myogenic cells. When either MyoD or myogenin cDNA was
      introduced into C3H10T1/2 (10T1/2) cells with a muscle-specific CAT reporter
      containing four copies of the right E-box of muscle creatine kinase (MCK)
      enhancer, the CAT activity was dose-dependently suppressed by BMP-2. Furthermore,
      BMP-2 inhibited the terminal differentiation of these subclonal 10T1/2 cells that
      stably expressed MyoD or myogenin into mature myotubes that expressed myosin
      heavy chain and troponin T. The differentiation of a subclone of the MyoD
      transfected NIH3T3 cells into mature muscle cells was also inhibited by BMP-2.
      BMP-2 induced alkaline phosphatase activity in 10T1/2-derived, but not in NIH3T3
      derived MyoD-transfected cells. These cells constitutively expressed exogenous
      MyoD and myogenin, which were localized exclusively in the nuclei irrespective of
      the presence and the absence of BMP-2. However, these cells failed to express the
      mRNAs of endogenous myogenic factors and MCK when cultured with BMP-2. In the
      electrophoresis mobility shift assay using nuclear extracts of the myogenic
      cells, MyoD and myogenin bound to the right E-box in the enhancer region of the
      MCK gene even in the presence of BMP-2. These results suggest that BMP-2 inhibits
      the terminal differentiation of myogenic cells by suppressing the transcriptional
      activity of the myogenic factors.

PMID- 9024795
TI  - IDS transfer from overexpressing cells to IDS-deficient cells.
AB  - Iduronate sulfatase (IDS) is responsible for mucopolysaccharidosis type II, a
      rare recessive X-linked lysosomal storage disease. The aim of this work was to
      test the ability of overexpressing cells to transfer IDS to deficient cells. In
      the first part of our work, IDS processing steps were compared in fibroblasts,
      COS cells, and lymphoblastoid cell lines and shown to be identical: the two
      precursor forms (76 and 90 kDa) were processed by a series of intermediate forms
      to the 55- and 45-kDa mature polypeptides. Then IDS transfer to IDS-deficient
      cells was tested either by incubation with cell-free medium of overexpressing
      cells or by coculture. Endocytosis and coculture experiments between transfected
      L beta and deleted fibroblasts showed that IDS transfer occurred preferentially
      by cell-to-cell contact as IDS precursors are poorly secreted by transfected L
      beta. The 76- and 62-kDa IDS polypeptides transferred to deleted fibroblasts were
      correctly processed to the mature 55- and 45-kDa forms. L beta were not able to
      internalize the 90-kDa phosphorylated precursor forms excreted in large amounts
      in the medium of overexpressing fibroblasts. Enzyme transfer occurred only by
      cell-to-cell contact, but the precursor forms transferred in L beta after cell-to
      cell contact were not processed. This absence of maturation was probably due to a
      mistargeting of IDS precursors in these cells.

PMID- 9024796
TI  - beta-amyloid-induced endothelial necrosis and inhibition of nitric oxide
      production.
AB  - Deposits of amyloid beta-peptide (A beta) in senile plaques and cerebral blood
      vessels is the prominent feature of Alzheimer's disease (AD), regardless of
      genetic predisposition. The cellular origin of cerebral deposits of A beta or its
      precise role in the neurodegenerative process has not been established. Recently
      we demonstrated a novel action of beta-amyloid on blood vessels--vasoactivity and
      endothelial damage through superoxide radicals. Since endothelial dysfunction is
      associated with vascular degenerative diseases, we examined the direct action of
      A beta on endothelial cells in culture. Cells treated with A beta displayed
      characteristics of necrotic cell death which was prevented by the free radical
      scavenging enzyme superoxide dismutase. Stimulation of endothelial nitric oxide
      (NO) production by the calcium ionophore, A23187, or bradykinin was inhibited by
      beta-amyloid. We conclude that an imbalance of NO and oxygen radicals may mediate
      the A beta-induced endothelial damage on endothelial cells in culture and may
      also contribute to a variety of pathophysiological conditions associated with
      aging: hypertension, cerebral ischemia, vasospasm, or stroke.

PMID- 9024797
TI  - Bone morphogenetic protein-2 is a regulator of cell adhesion.
AB  - Bone morphogenetic proteins (BMPs) are a group of peptide growth factors closely
      related to transforming growth factors-beta. The BMPs are suggested to play an
      essential role in bone development and they are strong candidate molecules to be
      used clinically to improve fracture healing. BMPs are also involved in the
      differentiation of several other tissues during embryogenesis. Here, we show that
      human recombinant BMP-2 regulates cell-matrix interactions by modifying the
      expression of integrin-type receptors. The synthesis of alpha3 integrin was down
      regulated by BMP-2 in two osteogenic sarcoma-derived cell lines, Saos-2 and HOS,
      and also in human fetal chondrocytes. BMP-2 had no effect on the expression of
      alpha1, alpha2, alpha5, alpha6, and alphaV integrins. BMP-2 reduced the
      expression of alpha3 integrin subunit at mRNA level. Laminin-5 was shown to be
      the ligand for alpha3beta1 integrin on Saos cells and BMP-2 decreased the ability
      of Saos cells to attach to it. These results suggest that BMP-2 has a specific
      effect on the alpha3beta1 integrin-mediated cell adhesion to laminin-5. Given the
      fact that BMP-2 is expressed in osteosarcomas, in addition to in bone, this
      mechanism is putatively important especially in bone development and tumors. We
      also studied the effect of BMP-2 on a human keratinocyte cell line, HaCaT. In
      HaCaT cells, the expression of alpha2 integrin was strongly down-regulated by BMP
      2, whereas its effect on the expression of alpha3 integrin was smaller. We
      suggest that the effects of BMP-2 may be partially mediated by specifically
      altered cell adhesion.

PMID- 9024798
TI  - Loss of intracellular putrescine pool-size regulation induces apoptosis.
AB  - Synthesis and uptake are two important regulated mechanisms by which eukaryotic
      cells maintain polyamine levels. The role that loss of synthesis and/or uptake
      regulation plays in mediating putrescine toxicity was investigated by comparing
      toxicity in an ornithine decarboxylase (ODC)-deficient Chinese hamster ovary cell
      line (C55.7) with a functional putrescine transport system and an ODC
      overproducing rat hepatoma cell line (DH23b), which are transport regulation
      deficient. When C55.7 cells were transfected with either mouse ODC (M) or
      trypanosome ODC (Tb), intracellular putrescine content increased slightly in
      C55.7(Tb-ODC), compared to C55.7(M-ODC), due to the lack of response of Tb-ODC to
      polyamine regulation. The increase in putrescine content resulting from loss of
      ODC regulation had no impact on cell growth and viability. When the feedback
      repression of polyamine uptake was blocked with cycloheximide, C55.7 cells
      transfected with either ODC construct accumulated very high levels of putrescine
      from the medium, and underwent apoptosis in a putrescine dose-dependent manner. A
      similar correlation of deregulated putrescine uptake and increased apoptotic
      cells was observed in DH23b cells. These data demonstrate that loss of feedback
      regulation on the polyamine transport system, but not ODC activity, is sufficient
      to induce apoptosis. Thus, downregulation of the transport system is necessary to
      prevent accumulation of cytotoxic putrescine levels in rodent cells.

PMID- 9024799
TI  - Characterization and distribution of O-glycosylated carbohydrates in the cell
      adhesion molecule, contact site A, from Dictyostelium discoideum.
AB  - This paper presents further investigation of the properties of carbohydrate II in
      the cell adhesion molecule, contact site A, from Dictyostelium discoideum. A
      purified contact site A was digested with Achromobacter protease I to produce a
      31-kDa fragment to which carbohydrate II was mainly bound and a 21-kDa fragment
      containing the NH2 terminus of contact site A, which was identified as Ala-Pro
      Thr-Ile-Thr-Ala. The NH2 terminus of the 31-kDa fragment was Thr-Glu-Ala-Thr-Thr
      Ser. It was estimated from the cDNA sequence data of contact site A that more
      than 20 Ser/Thr residues exist as target sites for the O-linked oligosaccharides
      in the 31-kDa fragment, but not for the N-linked oligosaccharides. These results
      suggest that carbohydrate II exists as clustered O-linked oligosaccharides in the
      COOH terminus of contact site A. The results of two-dimensional electrophoresis
      confirm that oligosaccharides of contact site A contain sialic acids.
      Immunoelectron microscopy was carried out to define the organelle in which O
      glycosylation by carbohydrate II occurs and how carbohydrate II antigens are
      distributed on the cell surface. The results show that O-glycosylation can occur
      in the Golgi apparatus in D. discoideum as observed in other cells, although this
      O-glycosylation was inhibited by tunicamycin. Furthermore, gold particles were
      densely concentrated in cell-cell contact regions but sparsely distributed in
      noncontact regions.

PMID- 9024800
TI  - Different strategies of X-inactivation in germinal and somatic cells: histone H4
      underacetylation does not mark the inactive X chromosome in the mouse male
      germline.
AB  - It has previously been shown by immunocytochemistry that the inactive X
      chromosome (Xi) in somatic cells of human and mouse females is marked by
      underacetylation of histone H4. It has been suggested that this may be important
      for transcriptional silencing of genes on Xi. We have now investigated X
      inactivation in meiotic cells of the male germline. In these cells the single X
      chromosome is transcriptionally inactive and expresses XIST, a gene that in
      somatic cells is transcribed only from Xi. By immunostaining with antibodies to
      H4 acetylated at lysines 5, 8, 12, or 16, we demonstrate that histone H4 on the
      male X is not underacetylated. We conclude that there is a differential germline
      strategy for maintenance of X-inactivation and that H4 underacetylation, though
      associated with the long-term marking of inactive X chromosomes in the female
      soma, is not always essential for the transcriptional down-regulation of X-linked
      genes.

PMID- 9024801
TI  - Stimulation by DIF causes an increase of intracellular Ca2+ in Dictyostelium
      discoideum.
AB  - Using fluorescence-activated cell sorting (FACS), we have studied the effect of
      the differentiation-inducing factor (DIF) on cellular Ca2+ in Dictyostelium
      discoideum. We have shown previously that freshly starved or postaggregation
      amoebae are heterogenous with respect to the amounts of cellular Ca2+ that they
      contain; the L or "low Ca2+" class exhibits a prespore tendency and the H or
      "high Ca2+" class exhibits a prestalk tendency. Upon adding DIF, within 2 min
      there is an approximately twofold increase in the relative fraction of amoebae
      falling in the H class. A major part of the increase is caused by Ca2+ influx
      from the extracellular medium. Therefore a rise in the level of cellular Ca2+ is
      an early step in the signal transduction pathway following stimulation by DIF.
      Also, in parallel with the cellular heterogeneity in respect of Ca2+ content,
      there is a heterogeneity in the response to DIF, which appears to be restricted
      to L cells.

PMID- 9024802
TI  - Amplitude-dependent stress fiber reorientation in early response to cyclic
      strain.
AB  - Almost all types of cells in vivo are constantly subjected to mechanical
      deformation derived from muscular movement, respiration, or blood pulsation. In
      order to elucidate how cells and their cytoskeletal components respond to these
      stimuli, we developed a new device which can apply a wide range of uniaxial
      cyclic strain to cultured cells. When the cells were subjected to this
      stimulation, their stress fibers were rapidly arranged at a specific oblique
      angle relative to the direction of stretching. This stress fiber angulation
      showed a close relationship to the amplitude of stretching.

PMID- 9024803
TI  - The effect of space flight on monoclonal antibody synthesis in a hybridoma mouse
      cell line.
AB  - The hybridoma cell line, 3G10G5, producing a monoclonal antibody to the major
      capsid protein VP1 from the avian polyomavirus budgerigar fledgling disease
      virus, was produced from a Balb/C mouse. This cell line was used to test the
      effects of microgravity on cellular processes, specifically protein synthesis. A
      time course study utilizing incorporation of [35S]methionine into newly
      synthesized monoclonal antibody was performed on STS-77. After 5.5 days, it was
      observed that cell counts for the samples exposed to microgravity were lower than
      those of ground-based samples. However, radiolabel incorporation of the
      synthesized monoclonal antibody was similar in both orbiter and ground control
      samples. Overall, microgravity does not seem to have an effect on this cell
      line's ability to synthesize IgG protein.

PMID- 9024804
TI  - Modulation of bovine papillomavirus DNA replication by phosphorylation of the
      viral E1 protein.
AB  - E1 is the DNA replication origin recognition protein for bovine papillomavirus
      (BPV), and it carries out enzymatic functions required for initiation of viral
      DNA replication. Cellular mechanisms likely play a role in regulating BPV DNA
      replication. We are investigating the role of phosphorylation of E1 on viral
      replication in vivo and on E1 activity in vitro. Serine 109 is a phosphoacceptor
      in vivo and is targeted by protein kinase A and protein kinase C in vitro. A
      viral genome carrying a serine 109 to alanine mutation replicates more
      efficiently than wild-type in vivo in a transient replication assay. Furthermore,
      purified mutant protein, while having wild-type levels of ATPase activity, is
      able to bind more origin-containing DNA than wild-type E1. Phosphorylation
      therefore appears to play a selective role in modulating a specific E1 function
      during viral DNA replication.

PMID- 9024805
TI  - Binding of the ubiquitous cellular transcription factors Sp1 and Sp3 to the ZI
      domains in the Epstein-Barr virus lytic switch BZLF1 gene promoter.
AB  - Induction of the Epstein-Barr virus lytic cycle in latently infected B cells
      requires the expression of the immediate-early lytic gene BZLF1. We have
      previously identified several cis-elements within the BZLF1 promoter that are
      required for induction by known inducers of the lytic cycle [E. Flemington and S.
      H. Speck (1990)J. Virol. 64, 1217-1226]. These include four elements termed the
      ZI domains (ZIA, ZIB, ZIC, and ZID) that share extensive homology and that have
      recently been shown to bind several cellular transcription factors [A. M. Borras,
      J. L. Strominger, and S. H. Speck (1996) J. Virol. 70, 3894-3901]. Here Sp1 and
      Sp3 are identified as the cellular factors present in crude B cell nuclear
      extract preparations that bind to the ZIC domain. In addition, three of the four
      complexes observed in electrophoretic mobility shift analyses employing probes
      containing either the ZIA or the ZID domains also represent Sp1 or Sp3 binding.
      Binding of Sp1 and Sp3 to the ZI domains was shown to be significantly weaker
      than binding of these factors to a consensus Sp1 site. A heterologous promoter
      construct containing three repeats of a consensus Sp1 site, cloned upstream of a
      single copy of the ZII (CREB/ AP1) element from the BZLF1 promoter linked to the
      beta-globin TATA box, exhibited phorbol ester inducibility. The latter
      observation was consistent with the functional behavior exhibited by a
      heterologous promoter construct containing multiple copies of the ZIC domain
      liked to the ZII element. However, the basal activity of the heterologous
      promoter construct driven by the consensus Sp1 sites was ca. 10-fold higher than
      that of the heterologous reporter construct containing multimerized ZIC sites.
      Thus, the low affinity of Sp1 binding to the ZI domains may contribute to the low
      level basal activity of the BZLF1 promoter.

PMID- 9024806
TI  - Characterization of JKT-7400, an orbivirus which grows in Aedes albopictus
      mosquito cells: evidence pointing to a minor virion protein, VP6, as the RNA
      guanylyltransferase.
AB  - JKT-7400 virus, an orbivirus originally isolated from Culex mosquitos, was plaque
      purified and adapted to Aedes albopictus mosquito cells. Conditions which enhance
      viral cytopathic effect and optimize plaque formation are described. In contrast
      to bluetongue virus, the prototype orbivirus, no replication of JKT-7400 virus in
      vertebrate cells was observed. The core particle of JKT-7400 virus contains 10
      segments of dsRNA and three minor proteins, VP1, VP4, and VP6. The inner shell
      contains two major proteins, VP2 and VP7, and the outer shell consists of the
      other two major proteins, VP3 and VP5. Evidence is presented suggesting that the
      viral protein associated with the capping of virus mRNA, i.e., the
      guanylyltransferase, is VP6, one of the core proteins.

PMID- 9024807
TI  - Characterization of Rev function using subgenomic and genomic constructs in T and
      COS cells.
AB  - The effect of the human immunodeficiency type 1 (HIV-1) Rev protein on the
      splicing and cytoplasmic accumulation of HIV-1 RNAs was investigated in COS and T
      cells. Subgenomic and genomic constructs were used which expressed varying levels
      of complexity in their potential RNA constituents. Using all constructs, in both
      cell types, an inhibitory effect of Rev on the level of fully spliced HIV-1 RNAs
      could be demonstrated. An increase in the nuclear level of unspliced pre-mRNA was
      seen in the presence of Rev with genomic constructs. Thus, the inhibitory effect
      on splicing was not merely due to enhancement of nuclear export of the pre-mRNA
      with these constructs. In both cell types, a positive effect of Rev on the
      cytoplasmic accumulation of HIV-1 RNAs could also be seen. However, in T cells,
      the Rev-dependent RNAs were still capable of accumulating at a reduced level in
      the cytoplasmic fraction in the absence of Rev. The identity of the cell type,
      construct, and RNA species impacted on the phenotypic manifestation of Rev
      function.

PMID- 9024808
TI  - Functional analysis of the transmembrane anchor region of bovine herpesvirus 1
      glycoprotein gB.
AB  - In herpesviruses, homologues of glycoprotein B (gB) are essential membrane
      proteins which are involved in fusion. However, there is no clear evidence
      regarding the location of the fusogenic domain on gB. By using bovine herpesvirus
      1 (BHV-1) as a model, we studied the relationship between the structure and the
      fusogenic activity of gB. This was achieved by expressing genes of different gB
      derivatives containing specific truncations at the end of segments 2 or 3 of the
      transmembrane region in Madin-Darby bovine kidney cells under the control of the
      bovine heat-shock protein hsp70A gene promoter. All expressed gB products were
      structurally similar to authentic gB. One truncated form of gB, gBt, which
      contains residues 1-763, was efficiently secreted. However, gBtM (residues 1
      807), which includes the first two segments at the carboxyl terminus, showed
      unstable retention on the cell surface, whereas gBtMA (residues 1 829), which
      contains all three membrane-spanning segments, was mostly intracellularly
      retained with some unstable surface anchorage. Another truncated gB, gBtDAF,
      which has gB residues 1-763 (gBt) and a human decay-accelerating factor (DAF)
      carboxyl tail, was also expressed. The DAF fragment provided a signal for the
      addition of a glycosyl phosphatidylinositol-based membrane anchor, which could
      target the gBt chimeric protein on the cell membrane. Immunofluorescence staining
      and pulse-chase kinetic studies support the theory that gBtM, gBtMA, and gBtDAF
      are retained on nuclear and cellular membranes via different segments of the
      transmembrane region or the DAF fragment, respectively. For the cells expressing
      gBt or gBtM, no cell fusion was observed, whereas cells expressing gBtMA clearly
      showed fusion. However, in gBtDAF cells, the overexpression and cellular
      accumulation of recombinant gB products did not cause fusion either, which
      supports our contention that the fusion phenomenon in gBtMA cells is caused by
      the fusogenic activity of the expressed gBtMA. With the help of sequence
      analysis, our results indicate that segment 2 of the transmembrane anchor region
      might be a fusogenic domain, whereas the real anchor is segment 3.

PMID- 9024809
TI  - Normal cellular replication of Sendai virus without the trans-frame,
      nonstructural V protein.
AB  - The Sendai virus V protein is a nonstructural trans-frame protein in which a
      highly conserved cys-rich Zn2+-binding domain is fused to the N-terminal half of
      the P protein via mRNA editing. Using a recently developed system in which
      infectious virus is recovered from cDNA, we have engineered a virus in which a
      translation stop codon was placed at the beginning of the V ORF. Translation of
      the V(stop) mRNA yields a W-like protein, i.e., a protein composed of the N
      terminal half of the P protein alone which is naturally expressed at low levels
      from the P gene. This V-minus but W-augmented virus was found to replicate
      normally in cell culture and embryonated chicken eggs. The Sendai virus V protein
      is thus an accessory protein, and the cys-rich Zn2+-binding domain is likely to
      function in a specialized role during virus propagation.

PMID- 9024810
TI  - In vitro mutational and inhibitory analysis of the cis-acting translational
      elements within the 5' untranslated region of coxsackievirus B3: potential
      targets for antiviral action of antisense oligomers.
AB  - The 5' untranslated region (5'UTR) of coxsackievirus B3 (CVB3) RNA forms a highly
      ordered secondary structure that has been implicated in controlling initiation of
      viral translation by internal ribosomal entry. To test this hypothesis, synthetic
      bicistronic RNAs, with all or part of the 5'UTR in the intercistronic space, were
      translated in rabbit reticulocyte lysates. In the presence of an upstream
      cistron, the chloramphenicol acetyltransferase gene, designed to block ribosomal
      scanning, the CVB3 5'UTR was capable of directing the internal initiation of
      translation of the downstream reporter gene (P1), confirming the presence of an
      internal ribosomal entry site (IRES). This finding was further supported by the
      data on predicted secondary structures within the 5'UTR. Of special note,
      analysis of various deletion mutants demonstrated that the IRES of CVB3 is
      located roughly at stem-loops G, H, and I spanning nucleotides (nt) 529 and 630.
      The region from nt 1 to 63 (stem-loop A) also appears important, and it may be an
      essential binding site for translation initiation factors. Based on these
      findings, in vitro translation inhibition assays using RNA fragments of the 5'UTR
      as inhibitor were performed. Both antisense and sense RNA segments transcribed
      from these two cis-acting regions and the surrounding sequence of the initiation
      codon AUG showed strong inhibition of viral protein synthesis. Antisense
      molecules may inhibit translation by blocking ribosome and initiation factor
      binding within the 5'UTR via specific hybridization to their viral RNA target
      sequences, while sense sequences may function by competing with viral RNA for
      ribosomes and/or translation initiation factors. These cis-acting translational
      elements may serve as potential targets for the antiviral action of oligomers.

PMID- 9024811
TI  - Identification of mutations in a Sindbis virus variant able to establish
      persistent infection in BHK cells: the importance of a mutation in the nsP2 gene.
AB  - Sindbis virus is a positive strand RNA virus that has provided a valuable model
      for studying virus structure and replication. It is also being developed as a
      vector for the expression of heterologous proteins. Many studies with this virus
      are carried out in cultured BHK cells where infection is usually highly
      cytopathic and within 1 or 2 days after infection all of the cells are dead.
      Weiss et al. had established a persistently infected culture of BHK cells by
      infecting the cells with a virus preparation highly enriched in defective
      interfering (DI) particles and had isolated an attenuated virus, SIN-1 virus,
      from the culture [Weiss et al. (1980) J. Virol. 33, 463-474]. SIN-1 virus, free
      of DI particles, was able to establish a persistent infection in BHK cells. We
      initiated studies to determine what changes in the genome of the virus were
      responsible for this phenotype. We describe here the cDNA cloning and sequencing
      of the 5' terminus and the four nonstructural protein genes from SIN-1 virus. A
      single coding mutation in the nsP2 gene (a predicted change of Pro-726 --> Ser)
      produced a virus that was able to establish persistent infection in BHK cells.
      Additional mutations in the other genes were required to decrease the synthesis
      of viral RNA to a level similar to that found in cells infected with SIN-1 virus.
      Incorporation of the nsP2 mutation into a Sindbis virus expression vector led to
      a higher level of synthesis of the reporter protein, beta-galactosidase, than
      that obtained with the original Sindbis virus replicon.

PMID- 9024812
TI  - Proviral organization and sequence analysis of feline immunodeficiency virus
      isolated from a Pallas' cat.
AB  - The nucleotide sequence and genomic organization have been determined for a
      highly cytopathic feline immunodeficiency virus (FIV) isolated from a Pallas'
      cat. The 9747-bp provirus of this virus, FIV-Oma, has typical lentivirus
      organization with LTRs, gag, pol, and env open reading frames (ORFs), putative
      vif and rev ORFs, and an ORF similar to ORF2/ORFA of domestic cat FIV isolates.
      Although the FIV-Oma provirus is 300 to 600 bp longer than other FIV proviruses,
      these additional bases are distributed throughout the genome. Phylogenetic
      analysis of a conserved region of the pol gene suggests that FIV-Oma is more
      closely related to some of the puma and lion lentiviruses than it is to domestic
      cat FIV isolates; however, many regions of the genome exhibit extensive
      nucleotide sequence divergence. None of the eight molecular proviral clones
      isolated from a genomic library are infectious, but we have constructed an
      infectious, cytopathic clone of FIV-Oma from subcloned and PCR-amplified
      fragments of these proviral clones. This clone will be useful for identifying the
      genetic determinants of FIV-Oma's biological activities.

PMID- 9024813
TI  - Kinetics of accumulation of citrus tristeza virus RNAs.
AB  - Citrus tristeza virus (CTV), a member of the closterovirus group, is one of the
      more complex single-stranded RNA viruses. The 5' portion of its 19,296-nt, single
      stranded RNA genome is expressed as an approximately 400-kDa polyprotein that is
      proteolytically processed, while the 10 3' open reading frames are expressed from
      3'-coterminal subgenomic RNAs (sg RNAs). As an initial examination of the gene
      expression of this virus, we found that the kinetics of accumulation of genomic
      and sg RNAs and coat protein of the T36 isolate of CTV were similar in
      protoplasts of the natural host, citrus, and the experimental nonhost Nicotiana
      benthamiana. Newly synthesized genomic RNA was detected 2 days postinoculation
      and increased to a maximum at 3-5 days. The RNA complementary to the full-length
      virion RNA increased with similar kinetics, but at approximately one-tenth the
      concentration of genomic plus strands. Most of the abundant sg RNAs also
      accumulated in parallel to that of the genomic RNA. However, the smallest sg RNA,
      which corresponds to the p23 gene, increased earlier. The different sg RNAs
      accumulated in greatly differing amounts, in general with 3'-most sg RNAs
      accumulating to higher levels than 5' sg RNAs. However, some 3' sg RNAs (p13 and
      p18) accumulated to low levels. The two 3'-most sg RNAs (p23 and p20) accumulated
      to high levels approximately equal to that of the genomic RNA. The accumulation
      curve for coat protein paralleled that of its mRNA, suggesting that its
      regulation was transcriptional. Progeny virions from protoplasts were used to
      sequentially infect new protoplasts, serving as a potential source of virus that
      could evolve free from the genetic selection in intact plants for aphid
      transmission and movement.

PMID- 9024814
TI  - Autographa californica nuclear polyhedrosis virus p143 gene product is a DNA
      binding protein.
AB  - We have identified the protein product of the Autographa californica nuclear
      polyhedrosis virus (AcMNPV) p143 gene by constructing a recombinant baculovirus
      overexpressing the gene product P143. The overexpressed protein exhibited a
      relative mobility of approximately 140 kDa and was stable for at least 12 hr
      after synthesis. Immunoblotting using a monoclonal antibody developed against the
      overexpressed protein identified a similar polypeptide in AcMNPV-infected cells
      which was detectable by 4 hr postinfection. P143 was present within infected cell
      nuclei at relatively constant amounts until at least 72 hr after infection,
      suggesting that P143 may perform other functions at late times after infection.
      P143, purified from infected cell nuclei by chromatography over hydroxylapatite
      and DNA cellulose, bound in a sequence-independent fashion to double-stranded but
      not to single-stranded DNA to form a ladder of retarded protein-DNA complexes.
      Together, these data are consistent with the essential role of P143 for viral DNA
      replication and suggest that P143 may function by direct binding to DNA.

PMID- 9024815
TI  - Hepatitis C virus genomic variability in untreated and immunosuppressed patients.
AB  - To investigate whether immune pressure enhances the genetic diversity of the
      hepatitis C virus (HCV) hypervariable region 1, nucleotide sequences were
      compared in multiple sera, collected longitudinally, from three untreated
      patients and four patients undergoing liver transplantation for HCV-related
      cirrhosis. A minor variant became dominant in three of three patients following
      transplantation and persisted unchanged for months. Compared with untreated HCV
      carriers, transplant recipients had fewer quasispecies, fewer nucleotide changes
      (1.61 and 2.58/month), fewer amino acid sequence changes (0.40 and 1.94/month),
      as well as higher ratio of transitional to transversional mutations (2.57 and
      0.98, P < 0.02) and lower replacement to silent mutations (1.33 and 8.21, P <
      0.01). The two patients with the least genomic variation died of HCV graft
      infection. The data suggest that HCV variants which infect the graft are selected
      by recipient immune pressure at the time of transplant and that preferential
      replication in the graft is enhanced by routine immunosuppression.

PMID- 9024816
TI  - The morphology of the immature HIV-1 virion.
AB  - Newly released HIV-1 particles exhibit an immature morphology, previously
      reported to be characterized by a doughnut/ring-shaped structure. In this study
      we showed that among immature extracellular virus particles not only were
      particles with doughnut-shaped morphology present, but particles with a crescent
      morphology were also observed. These particles occurred with different
      frequencies, depending on whether they were in the cell or in cell-free
      fractions. The crescent-shaped particles were more abundant in the cell-free
      fractions, whereas the particles in the cell fraction mainly exhibited doughnut
      shaped morphology. The crescent-shaped structure may represent an assembly
      intermediate.

PMID- 9024817
TI  - Both pre-S1 and S domains of hepatitis B virus envelope proteins interact with
      the core particle.
AB  - The three envelope proteins of the hepatitis B virus (HBV) are encoded by a
      single open reading frame in the genome containing three separate in-phase AUG
      codons. This organization defines three protein domains (pre-S1, pre-S2, S) which
      form the small (S), middle (M, pre-S2/S), and large (L, pre-S1 /pre-S2/S)
      proteins. Mature virions are generated by the budding of preformed nucleocapsids
      through endoplasmic reticulum (ER) membranes containing S and L proteins, whereas
      the M protein is not necessary. This suggests an important function for the pre
      S1 domain. To investigate the protein-protein interactions involved during the
      maturation process of the HBV virion, we studied in vitro the binding affinity to
      purified HBV core particles of various synthetic peptides identical to regions of
      the envelope proteins. Data previously obtained with deletion mutants were
      confirmed and refined. The 13 C-terminal amino acids of pre-S1 bound efficiently
      to core particles, whereas other pre-S domains did not. Moreover, the amino acid
      sequence 56-80 in the cytosolic loop of S bound efficiently to the HBV core. This
      double interaction between the HBV capside and both S and pre-S1 domains may be
      required for virion morphogenesis.

PMID- 9024818
TI  - Restricted redox oscillation in oxidative phosphorylation in jaundiced rat liver
      mitochondria and its relation to calcium ion.
AB  - High morbidity and mortality in surgical management for patients with obstructive
      jaundice was greatly attributed to the metabolic derangements in jaundiced liver
      mitochondria. Isolated liver mitochondria from jaundiced rat, produced by common
      bile duct ligation, were used to study the relationship among NADH level, oxygen
      consumption, and extramitochondrial calcium concentration. Alterations in NADH
      percentage and oxygen consumption were accomplished by incubating mitochondria
      with different substrates and monitoring oxygen consumption and NAD(P)H
      fluorescence simultaneously. In jaundiced liver mitochondria with glutamate +
      malate as substrate, respiration increased after the addition of exogenous Ca2+
      at concentrations of 1 x 10(-7), 5 x 10(-7), and 1 x 10(-6) M. The maximal effect
      occurred at 5 x 10(-7) M. With different NADH-related substrates, the NAD(P)H
      fluorescence measurements (X axis) correlated linearly with state 3 respiration
      (Y axis), the slopes of the correlation curves being 2.27 and 0.79 in control and
      jaundiced mitochondria, respectively. After the addition of 5 x 10(-7) M Ca2+,
      the respirations of both control and jaundiced mitochondria increased and the
      slope for jaundiced mitochondria rose to 1.67. The matrix free Ca2+ concentration
      in jaundiced mitochondria, measured by fluo-3 loading, was higher than that in
      controls (162.1 +/- 16.7 nM, vs 129.7 +/- 12.6 nM, P < 0.01), while the matrix
      free/total Ca2+ ratio decreased from 34.9 +/- 6.0 (x10(-6)) to 27.2 +/- 4.4 (x10(
      6), 9- < 0.05. The amplitude of the change in NAD(P)H fluorescence was reduced in
      jaundiced rat liver mitochondria and this correlated with the depression of
      respiration. A decrease in free/total Ca2+ ratio may be closely related to
      mitochondrial respiratory impairment in jaundice.

PMID- 9024819
TI  - Comparative in vitro analysis of topical hemostatic agents.
AB  - Hemostatic agents are broadly utilized across the surgical specialties. While
      specific characteristics desirable for individual applications may vary, these
      agents generally are expected to aid the patient's coagulation system in the
      rapid development of an occlusive clot. Six commonly utilized hemostatic agents
      were quantitatively compared in terms of their ability to mediate platelet
      aggregation, deposition and activation, and initiate gross clot formation in a
      series of in vitro tests. Three types of collagen sponges (Actifoam, Helistat,
      Instat), microfibrillar collagen (Avitene), a gelatin sponge (Gelfoam), and
      oxidized regenerated cellulose (Surgicel) were studied. Platelet aggregation:
      Citrated platelet rich plasma (PRP) was contacted with hemostatic agents both
      with and without thrombin in a stirred cuvette and the platelet count was
      measured over 5 min. Platelet deposition: To approximate arterial wounds, PRP was
      perfused in a controlled manner through hemostatic agents, and the effluent
      platelet count was measured over time. Platelet activation: ATP secretion from
      PRP contacted with hemostatic agents in a stirred cuvette was measured at 1 and 5
      min. Clot formation: The clotting time of nonanticoagulated whole blood contacted
      with the hemostatic agents was measured. Materials which depleted platelets most
      rapidly and effectively in the perfusion system (Avitene, Helistat, and Actifoam)
      were also the most effective inducers of platelet aggregation and secretion. Clot
      formation (likely to be platelet dependent) was also more rapid in this group. An
      overall activity ranking combined the relative performance of each hemostatic
      agent on the various tests: Actifoam approximately Avitene > Helistat >> Gelfoam
      > Instat > Surgicel. The activity ranking generally reflects the materials used
      in these agents (collagen > gelatin > oxidized regenerated cellulose), as well as
      their processing (chemical crosslinking in collagen sponges may lower activity).
      Such in vitro assessment of the relative platelet and coagulation activities of
      hemostatic agents might serve as a useful screening tool before investigating
      properties which require more expensive animal or clinical testing.

PMID- 9024820
TI  - Influence of perioperative catheter injury on the long-term vein graft function
      and morphology.
AB  - BACKGROUND: It has been shown that suboptimal preparation of a vein graft prior
      to its insertion results in immediate morphological and functional damage to both
      endothelial cells and underlying smooth muscle cells. This study examines the
      influence of perioperative balloon catheter injury on the subsequent development
      of intimal hyperplasia and vasomotor function in experimental vein grafts.
      METHODS: Twenty New Zealand White rabbits had a carotid vein bypass graft
      performed: 10 were controls and 10 had a balloon catheter passed through their
      lumen which resulted in deendothelialization and intramural injury (4Fr Fogarty
      catheter, 0.6-0.75 ml H20 inflation, three passes). All grafts were harvested
      after 28 days for either morphology (n = 6) or functional studies (n = 4; four 5
      mm rings/graft). RESULTS: Perioperative balloon injury of the vein graft resulted
      in a 23% increase in the intimal thickness (102 +/- 7 microm vs 83 +/- 2 microm,
      deendothelialized vs control; mean +/- SEM, P < 0.01) and a 67% increase in
      medial thickness (144 +/- 19 microm vs 86 +/- 8 microm; mean +/- SEM, P < 0.01)
      of the vein grafts. Both the sensitivity and maximal contraction of the responses
      elicited by norepinephrine, serotonin, and bradykinin were increased in the
      deendothelialized group compared to controls. CONCLUSION: Perioperative denuding
      balloon injury of the vein graft results in the increased development of intimal
      hyperplasia with an overall enhanced contractility. This study demonstrates the
      long-term structural and functional effects of perioperative balloon catheter
      injury on vein grafts that may contribute to decreased graft patency.

PMID- 9024821
TI  - Effect of aprotinin on smooth muscle cell proliferation, migration, and
      extracellular matrix synthesis.
AB  - Aprotinin (AP) is a plasmin inhibitor commonly used to limit bleeding during
      reoperative coronary bypass surgery. The effect on smooth muscle cell (SMC)
      behavior and the development of intimal hyperplasia has not been evaluated. This
      study examines the effect of AP on SMC proliferation, migration, and
      extracellular matrix synthesis. Bovine aortic SMCs (three to five passages)
      plated at 5 x 10(4) cells/ml were treated with 1.0, 10, 100, and 1000 microg/ml
      AP. Proliferation was measured as micrograms of DNA per well, after 3 days in
      culture. SMC migration was measured after treatment with mitomycin C (20
      microg/ml, to study migration in the absence of proliferation) by means of a
      fence assay. Extracellular matrix was quantitated utilizing a tritiated proline
      assay and corrected for cell density (cpm/microg DNA). Data are presented as
      means +/- SEM; ANOVA and post hoc Tuckey test were used to test for significant
      differences. AP stimulated SMC proliferation at dosages of 100 microg/ml (353 +/-
      6 microg DNA, SMC control vs 440 +/- 11, 100 microg/ml; P < 0.05) and 1000
      microg/ml (353 +/- 6, SMC control vs 503 +/- 14, 1000 microg/ml; P < 0.01). AP
      concentrations less than 100 microg/ml had no effect on SMC proliferation. A dose
      response relationship existed between AP and SMC migration. AP doses as low as 10
      microg/ml increased SMC migration from 66 +/- 4 mm2 (control SMC) to 90 +/- 4 mm2
      (P < 0.02) while the maximal dose of AP (1000 microg/ml) produced an almost
      twofold increase in migration (66 +/- 4, SMC control vs 113 +/- 3, 1000 microg/ml
      group; P < 0.0001). AP had no effect on extracellular matrix synthesis. AP
      stimulated vascular SMC migration and proliferation but not matrix synthesis in
      vitro. These data suggest that AP could augment the development of intimal
      hyperplasia following bypass surgery.

PMID- 9024822
TI  - Significance of serum delta bilirubin during obstructive jaundice in dogs.
AB  - BACKGROUND: delta-Bilirubin, a nonenzymatic covalently bound complex with
      albumin, is nonenzymatically formed in serum and has a long half-life
      irrespective of hepatorenal function. The aim was to examine if delta-bilirubin
      reflects the duration of obstructive jaundice and efficacy of biliary drainage.
      MATERIALS AND METHODS: Obstructive jaundice was developed in 17 dogs either for 4
      (short term; n = 9) or 11 (long term; n = 8) days and then external biliary
      drainage was performed. Serum total, direct, and delta-bilirubin fractions were
      analyzed by high-performance liquid chromatography. RESULTS: delta-Bilirubin was
      not detectable in serum before biliary obstruction. The serum total and direct
      bilirubin levels increased rapidly and reached a plateau within 2 days after the
      biliary obstruction, whereas the concentration and proportion of delta-bilirubin
      gradually increased and significantly correlated with the duration of obstructive
      jaundice. Before biliary drainage, the proportion of delta-bilirubin was 28.9 +/-
      2.4% in the short-term and 42.5 +/- 2.4% in the long-term obstruction group. The
      decline indices of serum total, direct, and total minus delta-bilirubin in the
      short-term group (-0.17, -0.19, and -0.26, respectively) were significantly (P <
      0.05) greater than those in the long-term obstruction group (-0.10, -0.10, and 
      0.13). The decline index of delta-bilirubin itself was similar between the
      groups. CONCLUSIONS: The concentration and proportion of delta-bilirubin in serum
      reflect the duration of jaundice. Because delta-bilirubin is not excreted into
      bile and urine and is not toxic to organs, a decline index of total bilirubin
      minus delta-bilirubin, the excretable bilirubin fraction might be better to
      assess the efficacy of biliary drainage.

PMID- 9024823
TI  - Suppression of pancreatic cancer by the dominant negative ras mutant, N116Y.
AB  - N116Y, H-ras mutant, possesses dominant negative activity to Ras function. The
      aim of this study is to assess whether N116Y can inhibit the proliferation of
      pancreatic cancer cell lines carrying K-ras mutations and cause reversion of the
      malignant phenotype. We transfected an expression vector of N116Y, pZIP-N116Y,
      into eight human pancreatic cancer cell lines with K-ras mutations (PCI 10, 19,
      24, 35, 43, 55, 64, and 66) by using a lipofection procedure. The growth
      inhibition activity of N116Y was evaluated by the colony-forming efficiency in
      selection medium. In order to examine the effect of N116Y on the neoplastic
      phenotype, we established N116Y-expressing clones and analyzed their growth
      ability in soft agar and tumorigenicity in nude mice. The growth of the eight
      pancreatic cancer cell lines was strongly inhibited by the transfection of pZIP
      N116Y. Moreover, the N116Y-expressing clones became less spread and lost their
      anchorage-independent growth ability. Furthermore, they were nontumorigenic in
      vivo. N116Y significantly inhibits the growth of pancreatic cancer cell lines and
      causes reversion of the malignant phenotypes. These results suggest that N116Y
      may be a candidate gene for use in the gene therapy of pancreatic cancer.

PMID- 9024825
TI  - Chronic perioperative steroids and colonic anastomotic healing in rats.
AB  - OBJECTIVE: To develop a rat model of long-term high-dose perioperative steroids
      and to evaluate the effects of these steroids on a colonic anastomosis in this
      model. DESIGN: Prospective randomized. METHODS: Twenty-six male Sprague-Dawley
      rats, weighing 270 to 330 g, were randomized into two groups. The first group
      (steroid group) (13 rats) received a time-release drug pellet (200 mg cortisone
      acetate in a 60-day release form) placed in the subcutaneous tissue of the
      posterior neck for an average daily dose of 3.3 mg. The second group (control
      group) (13 rats) received a placebo. At 6 weeks, blood cortisol levels were
      measured, and a colonic anastomosis was performed 2.5 cm distal to the cecum.
      Steroid group animals also received cortisone acetate (5 mg intramuscularly)
      immediately before surgery. Colonic bursting strength (mmHg) was measured at the
      anastomosis site and in the normal distal left colon using a saline infusion
      system at 8 and 12 days postoperatively. RESULTS: Blood cortisol levels were
      significantly higher in the rats in the steroid group than in the rats in the
      control group. The anastomotic bursting strength was significantly lower in the
      steroid group at Days 8 and 12. The bursting pressure of the unoperated left
      colon was not significantly different when the groups were compared. Also, in the
      steroid group, healing of the pellet insertion wounds in the neck was impaired.
      CONCLUSION: The time-release drug pellet is a reliable method of administering
      long-term steroids. Long-term perioperative steroids impaired colonic anastomotic
      healing, while normal tissue strength (left colon) was not significantly changed.

PMID- 9024824
TI  - 21-Aminosteroids block neutrophil infiltration and provide liver protection
      independent of NO2-/NO3- levels.
AB  - 21-Aminosteroids are antioxidant compounds that prevent iron-dependent lipid
      peroxidation and improve cell viability. In this work we attempt to define the
      role of 21-aminosteroids in liver ischemia and reperfusion and assess their
      possible mode of action, specifically their effect on neutrophil infiltration and
      nitrite/nitrate levels. Total liver ischemia for 90 min was produced in the rat
      with the use of a portosystemic shunt. Three groups of animals were studied. One
      group received the 21-aminosteroid U-74389G (10 mg/ kg) divided into two equal
      doses 10 min prior to ischemia (7 mg/kg) and 10 min before reperfusion (3 mg/
      kg). The two other groups included the sham and the control animals. We studied
      survival at 7 days and serum liver enzymes, liver myeloperoxidase, plasma
      nitrites, nitrates, and liver histology at 6 hr postreperfusion. Animal survival
      improved from 13% in the ischemic control to 52% in the lazaroid treated group (P
      < 0.05). We observed significant improvements in liver function tests, liver
      myeloperoxidase levels, as well as in the liver histology (P < 0.05). We could
      not find statistical difference in plasma nitrite/nitrate (P > 0.1). The 21
      aminosteroids significantly improved animal survival after total liver ischemia,
      through a mechanism that includes blocking neutrophil infiltration which is
      independent from nitrite/nitrate levels.

PMID- 9024826
TI  - Hepatic influence on pulmonary neutrophil sequestration following intestinal
      ischemia-reperfusion.
AB  - Intestinal ischemia-reperfusion (I/R) causes a myriad of systemic physiologic
      derangements including pulmonary neutrophil (PMN) sequestration, increased
      microvascular permeability, and adult respiratory distress syndrome. It has been
      suggested that the observed lung injury is mediated by transhepatic passage of
      portal venous blood from ischemic intestine resulting in hepatic Kupffer cell
      activation and cytokine secretion. The purpose of this investigation was to test
      the hypothesis that PMN sequestration and microvascular permeability reflect
      Kupffer cell activity and/or portal venous blood flow. Experiments were designed
      to independently test the contribution of (1) Kupffer cell activity and (2)
      portal venous blood flow. In the first set of experiments, Kupffer cells were
      eliminated by treatment with gadolinium chloride 10 mg/kg iv (KC-ablated, n =
      11). Control rats were treated with saline (KC-intact, n = 10). Intestinal
      ischemia was induced by SMA occlusion for 2 hr followed by 2 hr of reperfusion.
      In additional studies, the liver was excluded from the circulation by creation of
      a complete portosystemic shunt (portal vein to right femoral vein; shunt, n =
      23). Control rats were treated by insertion of a loop of tubing within the intact
      portal vein (sham, n = 23). Intestinal ischemia was induced by SMA occlusion for
      15 min followed by reperfusion for 1-3 hr. In both models, lung PMN accumulation
      and pulmonary microvascular permeability were assessed by myeloperoxidase (MPO)
      activity and 125I-albumin lung/blood ratio (AL/BR), respectively. Kupffer cell
      elimination had no effect on PMN accumulation (MPO: KC-intact 29 +/- 8 vs KC
      ablated 26 +/- 5 delta A/min/g; P = NS) or microvascular permeability (AL/BR: KC
      intact 0.22 +/- 0.01 vs KC-ablated 0.23 +/- 0.03; P = NS). Hepatic exclusion also
      had no effect on either PMN accumulation or permeability after reperfusion for 1
      hr (MPO: sham 38 +/- 12 vs shunt 42 +/- 14 delta A/min/ g; AL/BR: sham 0.24 +/-
      0.02 vs shunt 0.23 +/- 0.03; P = NS), 2 hr (MPO: sham 27 +/- 5 vs shunt 29 +/- 7
      delta A/min/g; AL/ BR: sham 0.29 +/- 0.02 vs shunt 0.26 +/- 0.05; P = NS), or 3
      hr (MPO: sham 24 +/- 12 vs shunt 32 +/- 7 delta A/min/g; AL/ BR: sham 0.33 +/-
      0.03 vs shunt 0.33 +/- 0.01; P = NS). In this animal model, pulmonary PMN
      sequestration and microvascular permeability following intestinal I/R are
      independent of hepatic portal blood flow and Kupffer cell activity.

PMID- 9024827
TI  - The effect of gabexate mesilate on pancreatic and hepatic microcirculation in
      acute experimental pancreatitis in rats.
AB  - Microcirculatory derangements are important early features in many organs during
      the process of acute pancreatitis. However, dynamic evaluation of these factors
      has been difficult. Antiprotease has long been used for the treatment of acute
      pancreatitis, although its effects and mechanism have not been fully elucidated.
      The involvement of proteases and microcirculatory derangement early in the course
      of acute pancreatitis are the main concern of this study. A severe acute
      pancreatitis model in male Sprague-Dawley rats (225-275 g) was established by
      adding caerulein (15 microg/kg/ hr) in intravenous infusion fluid and intraductal
      injection of 0.1 ml glycodeoxycholic acid (5 mM). Gabexate mesilate [GM; ethyl-4
      (6-guanidinohexanoyloxy)benzoate methanesulfonate], a synthetic antiprotease, was
      infused intravenously in doses of 0.01, 0.1, 1, and 10 mg as a therapeutic
      intervention in this model. Pathology hematocrit, serum amylase level, and
      glutamic-oxaloacetic transaminase (GOT) levels were used to confirm the severity
      of disease and effect of therapy. In vivo microscopic technique was used as a
      investigating tool in this study of microcirculatory derangement in pancreas and
      liver, 8 hr after induction of acute pancreatitis. GM can significantly improve
      pathologic criteria and changes of serum amylase levels in the range of 1-10
      mg/kg/hr. The severity of changes of hematocrit and GOT was significantly
      lessened with GM in the range of 0.1-10 mg/kg/hr. This agent also could improve
      the microcirculatory environment in pancreas and liver after induction of acute
      pancreatitis according to the parameters, such as flow velocity and rolling
      leukocyte phenomenon, in the range of 1-10 mg/kg/hr. According to our
      observation, severity of hyperpermeability had not changed with the treatment of
      GM. These results indicated the beneficial effects of GM on pancreatic and
      hepatic microcirculation early in the course of acute pancreatitis. The
      beneficial effects were noted in serum parameters and hematocrit. The importance
      of protease activation and remote organ dysfunction is emphasized in the course
      of acute pancreatitis from this study.

PMID- 9024828
TI  - Heparan preserves intestinal perfusion after hemorrhage and resuscitation.
AB  - BACKGROUND: Multiple system organ failure (MOF) remains a major source of
      morbidity and mortality in trauma patients. Despite restoration of central
      hemodynamics, intestinal hypoperfusion can persist. Mucosal ischemia and barrier
      breakdown are factors in the genesis of MOF. Heparan sulfate is a
      gycosaminoglycan similar to heparin, but with minimal anticoagulant properties.
      As an adjunct to resuscitation, it improves immunologic function and restores
      mucosal oxygenation and function. We hypothesized that resuscitation with heparan
      following hemorrhage wound prevents intestinal hypoperfusion. MATERIALS AND
      METHODS: In vivo videomicroscopy was used to study small intestine
      microcirculation in rats. Animals were hemorrhaged to 50% of baseline mean
      arterial pressure (MAP) and maintained there. Resuscitation was initiated when
      the return of 10% shed blood was required to keep MAP at 50%. Animals received
      either heparan (7 mg/kg/1 ml saline) or saline (1 ml) followed by the remaining
      shed blood and an equal volume of saline. MAP, cardiac output (CO), A1 arteriole
      diameters, and flow were determined. RESULTS: Resuscitation of the saline control
      group resulted in normal MAP with elevation of CO to 25-40% above baseline. The
      heparan group had return of MAP but only a moderate increase in CO (7-15%).
      Saline resuscitation led to progressive deterioration in A1 diameters and flow.
      The addition of heparan prevented delayed A1 constriction and significantly
      improved perfusion. CONCLUSIONS: Heparan prior to resuscitation improved
      intestinal perfusion, despite a relative reduction in CO. Improvement in nutrient
      blood flow may protect the mucosal barrier, reducing the incidence of MOF, and
      suggests that heparan may be useful in resuscitation of trauma patients.

PMID- 9024829
TI  - Changes in adenine nucleotides during hemorrhagic shock and reperfusion.
AB  - Certain tissues are known to be susceptible to shock-induced damage: liver, small
      bowel mucosa, and small bowel wall. This study was done to assess the changes in
      adenine nucleotides induced by hemorrhagic shock. Male Sprague-Dawley rats (n =
      21; 300-350 g) were anesthetized with sodium pentobarbital (50 mg/kg, ip) and
      mechanically ventilated. The external jugular vein and common carotid artery were
      cannulated. Laparotomy was done. Hemorrhagic shock was induced by withdrawing
      blood into a heparinized syringe until a mean arterial blood pressure of 40 mm Hg
      was obtained and was maintained for 30 min by continued withdrawals. Shed blood
      was then reinfused through the venous catheter. No additional fluid was
      administered. The animals were observed for another 60 min. Throughout the
      procedure, biopsies were taken of liver and small bowel. The small bowel biopsies
      were separated into mucosal and wall fractions. Nucleotides were extracted. ATP,
      ADP, AMP, adenosine, inosine, xanthine, and hypoxanthine were measured with
      gradient HPLC. Cellular ATP concentrations decreased significantly during shock
      (P < 0.05). Liver ATP dropped from 8.93 +/- 0.55 to 2.91 +/- 0.16 micromol/g dry
      tissue (mean +/- SEM) (33%), small bowel mucosal ATP from 9.40 +/- 1.04 to 3.26
      +/- 0.21 (35%), and small bowel wall ATP from 5.47 +/- 0.36 to 2.74 +/- 0.18
      (50%). The nucleotide response to shock in small bowel mucosa was closer to that
      of liver than to that of small bowel wall. After reperfusion, ATP levels were
      partially restored in liver, small bowel mucosa, and small bowel wall, but not to
      preshock values. All of the metabolites (adenosine, inosine, hypoxanthine, and
      xanthine) increased during shock (P < 0.05), and did not return to preshock
      levels after reperfusion. The abnormalities in ATP and its metabolites, and their
      persistence after reperfusion, suggest a possible mechanism for the production of
      postshock damage.

PMID- 9024830
TI  - Cardiac augmentation can be maintained by continuous exposure of intrinsic
      cardiac neurons to a beta-adrenergic agonist or angiotensin II.
AB  - The purpose of this work was to determine whether constant increases in cardiac
      rate and force can be induced by continuous exposure (20 min) of intrinsic
      cardiac neurons to pharmacological agents which activate such neurons. Intrinsic
      cardiac neurons within the ventral right atrial ganglionated plexus were
      activated by constant infusions of dobutamine or angiotensin II (100 microM/min
      for 10 min followed by 200 microM/min for 10 min) via their local arterial blood
      supply in 12 artificially ventilated, open chest anesthetized dogs while
      monitoring heart rate and indices of regional cardiac contractility. The results
      were as follows: (1) Dobutamine (100 microM/min for 10 min) enhanced intrinsic
      cardiac neuronal activity by 195% at first, neuronal activity declining
      thereafter to +79% of control values in the continued presence of this agonist.
      When the dose of dobutamine was doubled (200 microM/min for 10 min) neuronal
      activity increased +179% above control values and remained elevated, as did heart
      rate as well as right and left ventricular contractility. (2) Angiotensin II (100
      microM/min) increased neuronal activity at first, with neuronal activity
      decreasing gradually thereafter such that after 5 min of exposure activity
      reached control values. Neuronal activity did not increase further when neurons
      were subsequently exposed to a higher dose of angiotensin II (200 microM/min).
      Heart rate and ventricular contractility were increased initially more by
      angiotensin II than by dobutamine. However, cardiac indices fell thereafter
      concomitant with reductions in neuronal activity as the exposure to angiotensin
      II continued. Thus although cardiac rate and force initially were increased more
      by angiotensin II than by dobutamine, similar augmentation of cardiac indices was
      achieved by sustained exposure of a population of intrinsic cardiac neurons to
      either agent. In conclusion, heart rate and ventricular contractility can be
      enhanced for relatively prolonged periods of time by continuous exposure of a
      population of intrinsic cardiac neurons to a beta-adrenoceptor agonist or
      angiotensin II, with the beta-adrenoceptor agonist inducing more consistent
      cardiac augmentation than angiotensin II.

PMID- 9024831
TI  - Elution of six antibiotics bonded to polyethylene vascular grafts sealed with
      three proteins.
AB  - The elution of six antistaphylococcal antibiotics from vascular polyethylene
      grafts sealed with albumin, gelatin, or collagen were studied in an in vitro
      system. The antibiotics tested were pefloxacin, vancomycin, teicoplanin, fusidic
      acid, pristinamycin, and rifampicin. The grafts were impregnated by simple
      soaking in antibiotic (1 mg/ml). The data were fitted to an exponential model and
      antibiotic half-lives (t1/2) were calculated from the regression lines. All the
      antibiotics tested were bound to the protein sealants. Antibiotic release varied
      with the type of antibiotic and the sealant. Rifampicin was eluted most slowly,
      particularly with albumin- and gelatin-sealed grafts, with t1/2 at 4-5.5 hr and
      antibiotic activity was still found at 48 hr. The glycopeptides were also eluted
      more slowly from albumin or gelatin sealant than from collagen. Although large
      quantities of glycopeptides were initially bound, they were quickly eluted (t1/2
      = 30-44 min) and there was no residual antibiotic activity at 24 hr. Pefloxacin,
      pristinamycin, and fusidic acid bound to collagen or gelatin sealants were the
      most rapidly eluted, with t1/2 of 3-14 min, but they were eluted more slowly from
      albumin-sealed grafts, with t1/2 of 22-90 min. In vitro studies can be useful for
      evaluating the binding of antibiotics to protein-sealed grafts before animal
      experiments or human testing.

PMID- 9024832
TI  - Intravenous catecholamines alter hepatic blood flow in conscious dogs with
      experimental hepatic denervation.
AB  - Hepatic blood flow is regulated by the autonomic nervous system; however, blood
      flow through the denervated liver has been controversial. The purpose of this
      study is to evaluate the changes in hepatic blood flow caused by experimental
      hepatic denervation during the intravenous infusions of catecholamines (dopamine
      or dobutamine) with or without prior administration of alpha-adrenoceptor
      antagonist (phenoxybenzamine) or beta-adrenoceptor antagonist (propranolol). The
      liver blood flow was measured using transit time ultrasonic flow meter probes at
      the portal vein and hepatic artery in conscious dogs which (a) underwent hepatic
      denervation (denervation group, n = 9) and (b) were intact (control group, n =
      10). Norepinephrine concentrations in the liver were determined to evaluate the
      effects of hepatic denervation and were decreased at 1 week and 4 weeks after
      hepatic denervation. In the control group, dopamine and dobutamine produced an
      increase of portal venous blood flow (PVF). Conversely, hepatic denervation
      reduced the increase in PVF by dopamine and dobutamine. Dopamine with prior
      administration of phenoxybenzamine produced a much larger increase in PVF in both
      groups. Pretreatment of propranolol in both groups abolished the increasing
      effects of dopamine and dobutamine in PVF. Dopamine reduced the hepatic arterial
      blood flow (HAF) regardless of hepatic denervation. During dobutamine infusion,
      HAF was decreased by hepatic denervation and prior administration of propranolol.
      These results suggest that hepatic denervation reduces the increasing effects of
      catecholamines on the hepatic blood flow through greater enhancement of alpha
      adrenergic effects than of beta-adrenergic effects in the hepatic vascular
      autonomic nerve response.

PMID- 9024859
TI  - The growing importance of the plastid-like DNAs of the Apicomplexa.
AB  - Organisms in the phylum Apicomplexa possess, in addition to their mitochondrial
      genome, an extrachromosomal DNA that possesses significant similarities with the
      extrachromosomal genomes of plastids. To date, the majority of data on these
      plastid-like DNAs have been obtained from the human malarial organism, Plasmodium
      falciparum. In common with plastid DNAs, the plastid-like DNA of P. falciparum
      possesses genes for DNA-dependent RNA polymerase subunits beta and beta 1 and for
      organellar-like large- and small-subunits ribosomal RNAs. Both the polymerase
      subunit and ribosomal RNA gene sequences share a number of features with those
      from plastid DNAs. In addition, the ribosomal RNA genes are organised in an
      inverted repeat arrangement, reminiscent of plastid DNAs. Additional molecular
      features shared between the 2 genomes are discussed. Plastid-like DNAs have also
      been identified in other Plasmodium species as well as Toxoplasma gondii, Eimeria
      tenella, Babesia bovis and a number of Sarcocystis species. A cryptic organelle
      often observed in apicomplexans has been proposed as the organelle that harbours
      the plastid-like DNAs, but conclusive evidence for this has not yet been
      obtained. Although approximately 1/2 of the plastid-like DNA of P. falciparum has
      been sequenced to date, no function has yet been ascribed to this DNA or its
      putative organelle. Phylogenetic inferences based on sequence data from this DNA
      have indicated an evolutionary origin from photosynthetic organisms, but the true
      provenance of the plastid-like DNAs remains to be determined. Because of the
      specific nature of the plastid-like DNAs, they may prove useful as effective
      targets for chemotherapeutics.

PMID- 9024860
TI  - Implications of nutrition for the ability of ruminants to withstand
      gastrointestinal nematode infections.
AB  - Resistance and resilience of the ruminant host to gastrointestinal (GI) parasitic
      nematode infections are influenced by many factors, including nutrition. This
      review examines the effects of host nutrition on the ability of ruminants to
      withstand GI nematode infections. Firstly the effects of infection on host
      metabolism are summarised briefly. An important factor in the pathogenesis is a
      reduction in feed intake by the host. Gut nematodes also increase endogenous
      protein losses, which result in net loss of amino acids to the parasitised host,
      though energy and mineral metabolism are also perturbed. The indications are that
      the major nutritional change is in protein metabolism. Resilience (the ability of
      an animal to withstand the effects of infection) can be enhanced markedly by
      increasing metabolisable protein supply and to a lesser extent metabolisable
      energy supply. Resistance to GI nematodes (ability of host to prevent
      establishment and/or development of infection) is also influenced by diet,
      particularly metabolisable protein supply. While there do not appear to be any
      effects of host nutrition on establishment of infective larvae, the rate of
      rejection of adult worms can be enhanced by improved nutrition. The exact
      nutritional requirements or the mechanisms involved are not known. It appears
      that the effects of improving nutritional status on host resilience are more
      clearly defined than effects on host resistance. The implication of changes in
      host resistance with nutritional state for host productivity need to be better
      described. Understanding the role of nutrition in improving both resistance and
      resilience of the host to GI parasites will be important if producers are to make
      better use of host acquired immunity and reduce dependence on pesticides for
      prophylaxis.

PMID- 9024861
TI  - A revision of Heterocotyle (Monogenea:Monocotylidae) with a description of
      Heterocotyle capricornensis n. sp. from Himantura fai (Dasyatididae) from Heron
      Island, Great Barrier Reef, Australia.
AB  - Heterocotyle capricornensis n. sp. is described from the gills of Himantura fai
      collected from Heron Island, Great Barrier Reef, Australia. It is distinguished
      from other species in the genus by the morphology of the sclerotised male
      copulatory organ which is curved and tapered distally, the ovary which loops once
      before entering the oviduct, and the testis which has 3 posteriorly-directed
      lobes. The oncomiracidium of this species is also described. The homology between
      glands found in the oncomiracidium and the adult is discussed. Additional data
      based on the examination of type material and, in some cases, new material of
      previously described species are included. The genus is revised and a key to
      species is provided. Characters which unite the members of the genus could not be
      confirmed for Heterocotyle elliptica Pillai & Pillai, 1976 and H. robusta
      (Johnston & Tiegs, 1992) Price, 1938 and therefore we consider them species
      inquirendae. New host and locality records are presented for H. chinensis
      Timofeeva, 1983 and a new host record is presented for H. granulatae Young, 1967.
      Host-specificity and phylogenetic relationships in Heterocotyle are discussed.

PMID- 9024862
TI  - Hatching rhythms in the the capsalid monogeneans Benedenia lutjani from the skin
      and B. rohdei from the gills of Lutjanus carponotatus at Heron Island,
      Queensland, Australia.
AB  - Spontaneous hatching of eggs of Benedenia lutjani and B. rohdei occurred after
      incubation for 4-6 days and 6-10 days, respectively, at a constant temperature in
      the range 22-28 degrees C when exposed to natural illumination or to alternating
      12-h periods of light and darkness (LD12:12; light on, 06.00 h; light off, 18.00
      h). Under these conditions, hatching of the eggs of both species was rhythmical,
      all larvae emerging only during periods of illumination. Hatching was not
      confined to particular times with the illuminated period. Evidence for an
      endogenous component to the rhythm was revealed by transfer of eggs from LD12:12
      to continuous darkness (DD) near the end of the incubation period. Hatching, also
      occurred only during periods of illumination when eggs of each species were
      incubated under a DL12:12 regime (i.e. period of illumination 18.00 h to 06.0 h;
      period of darkness 06.00 h to 18.00 h). When the eggs of B. lutjani and B. rohdei
      were laid and incubated in DD or continuous illumination (LL), some degree of
      rhythmicity persisted, raising the possibility that the eggs inherit circadian
      rhythmicity from their parent. The hatching patterns of these 2 species of
      monogeneans are discussed in relation to host finding, host behaviour and limited
      observations on the behaviour of the oncomiracidia after hatching.

PMID- 9024863
TI  - The influence of intensity of infection by a trematode parasite on the
      reproductive biology of Gammarus insensibilis (Amphipoda).
AB  - Following the behavioural alterations induced by the trematode Microphallus
      papillorobustus Rankin 1940 (Trematoda, Microphallidae) on its second
      intermediate host, the amphipod Gammmarus insensibilis, infected individuals are
      likely to mate among themselves. We investigated the influence of parasite
      intensity on the reproductive biology of infected hosts. In the mating system of
      amphipods, males compete severely for access to females and large males have
      greater ability to obtain large and more fecund females. We showed that the null
      hypothesis of random pair formation according to parasite intensity could not be
      rejected. In addition, infected males obtained females of the expected size
      according to their own sizes, whatever their parasite intensities. However, in
      both males and females, the parasite intensity increased the intermoult duration.
      Because size and reproductive success are strongly correlated in amphipods, we
      discuss the influence of this process on host fitness.

PMID- 9024864
TI  - A chromosome study in the progenetic cestode Cyathocephalus truncatus
      (Cestoda:Spathebothriidea).
AB  - The chromosomes of somatic cells of progenetic Cyathocephalus truncatus, parasite
      of amphipod crustaceans, Gammarus lacustris, from North-West Chukotka were
      investigated using standard Giemsa staining. The karyotype, not described
      previously, consists of 9 pairs of chromosomes (2n = 18), the most widespread
      number among cestodes. A considerable number of polypoid cells (34.7%) was noted
      in preparations. The chromosomes are comparatively large, up to 12.26 microns.
      According to centromeric index values, chromosomes 1 and 4 subtelocentric; 2,
      acrocentric to subtelocentric; 3 and 5, acrocentric; 6 and 9, metacentric; 7
      submeta-subtelocentric; and 8, submetacentric. These characteristics are
      discussed with reference to the karyotypes previously described within other
      closely related groups caryophyllideans and pseudophyllideans.

PMID- 9024865
TI  - Ultrastructure of sensory endings in Diplostomum pseudospathaceum Niewiadomska,
      1984 cercariae (Digenea, Diplostomidae).
AB  - Using TEM techniques, 13 types of sensory endings were revealed on the body and
      tail of cercariae of D. pseudospathaceum. They differ in the presence or absences
      of cilia, number of cilia, number of electron-dense rings, basal body type and
      collar shape. The following groups of sensory endings were distinguished:
      uniciliate with a short (5 types), moderately long (one type) or long cilium (4
      types); multiciliate sensory pits (2 types); and nonciliate sensory bulbs. Most
      sensory endings with long cilium and nonciliate sensory bulbs were found on the
      tail stem. All the breviciliate sensory endings and multiciliate sensory tips, as
      well as 1 type with long cilium, were situated on the cercarial body. The
      uniciliate sensory endings with a moderately long cilium were found on the
      furcae. The ultrastructural variety of sensory endings in different groups of
      Digenea, as well as their supposed functions, are discussed.

PMID- 9024866
TI  - Efficacy in sheep and pharmacokinetics in cattle that led to the selection of
      eprinomectin as a topical endectocide for cattle.
AB  - Eprinomectin (MK-397 or 4"-epi-acetylamino-4"-deoxy-avermectin B1) is a novel
      avermectin selected for development as a topical endectocide for all cattle,
      including lactating cows. The initial efficacy assessments were made in sheep to
      identify subclasses of the avermectin/milbemycins that possessed inherent
      activity against a spectrum of nematode parasites. This included examination of
      several hundred analogs each given orally to a single sheep experimentally
      infected with a range of parasitic nematodes. Representatives of several
      subclasses, most notably the 4"-epi-amino avermectin B1 subclass, were identified
      as possessing potent, broad-spectrum activity against the endoparasites, whereas
      subclasses such as those with a variety of synthetic substitutions at C-4a or
      oximes at C-5 were among the least potent. Eprinomectin, a member of the 4"-epi
      amino subclass, possessed potent activity against the range of nematodes when
      tested at 0.025 mg kg-1 per os. Milk and plasma concentration profiles were also
      made for these and other selected avermectin/milbemycins following topical
      administration to lactating dairy cattle. The molecular structure of each
      compound had a significant effect on the milk to plasma ratio, but the ratio of
      each was constant over time, implying an equilibrium between the 2 compartments.
      Compounds that were saturated at the C-22,23 bond had milk to plasma ratios > or
      = 1.0, whereas those unsaturated at this bond were generally < or = 1.0. The milk
      to plasma ratio of eprinomectin was < or = 0.2. Therefore, not only is
      eprinomectin the most potent broad-spectrum avermectin/milbemycin identified to
      date, but it also possesses one of the lowest milk partitioning coefficients in
      this class of antiparasitics.

PMID- 9024867
TI  - Eprinomectin: a novel avermectin for use as a topical endectocide for cattle.
AB  - Eprinomectin (MK-397 or 4"-epi-acetylamino-4"-deoxy-avermectin B1) is a novel
      avermectin selected for development as a topical endectocide for all cattle,
      including lactating dairy cows. Herein, we show its anthelmintic, insecticidal
      and miticidal activity. To determine its anthelmintic capabilities, eprinomectin
      was tested topically on Jersey calves at 0.08, 0.2, or 0.5 mg kg-1 in a probe
      formulation against experimental infections of adult Haemonchus placei,
      ostertagia ostertagi, Trichostrongylus axei, T. colubriformis, Cooperia
      oncophora, C. punctata, Nematodirus helvetianus, Oesophagostomum radiatum and
      Dictyocaulus viviparus. Eprinomectin removed > or = 99% and > or = 98% of the
      adult stage of every species at the 0.5 and 0.2 mg kg-1 dosage levels,
      respectively. The lowest dosage (0.08 mg kg-1) produced maximal or near maximal
      efficacy against most of the adult endoparasites with the exception of T.
      colubriformis (87%) and C. oncophora (88%). In a separate test, eprinomectin was
      evaluated topically against the immature stages of species at the same dosages.
      Results showed > or = 99% and > or = 98% removal of the immature stages of each
      species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The 0.08 mg kg-1
      dosage maintained > or = 97% efficacy against 6 species with reduced activity
      against H. placei (42%) and N. helvetianus (66%). For ectoparasites, eprinomectin
      was tested topically at 0.16, 0.24, 0.32 or 0.5 mg kg-1 on mixed breed cattle
      naturally infested with the sucking louse, Linognathus vituli. Complete
      elimination of lice at all dosages was observed by day 14. Topical delivery of
      eprinomectin at 0.16, 0.24, 0.32 or 0.5 mg kg-1 to Holstein calves experimentally
      challenged with horn fly, Haematobia irritans, produced 100% efficacy to
      challenge by week 2 post-treatment in all dosages groups and 94% and 99% efficacy
      to challenge at the 0.32 and 0.5 mg kg-1 dosage groups, respectively, at week 4.
      Topical delivery of eprinomectin at 0.16, 0.24 or 0.5 mg kg-1 to Deutsches
      Fleckvieh cattle infested with mange mites, Chorioptes bovis, produced > or = 95%
      control at all dosages levels by day 14 post-treatment and was maintained at or
      near this efficacious level for the 6-week duration of the trial. No adverse
      reaction was observed in any animal in any of these tests. In summary, these
      experimental data indicate that eprinomectin is an excellent broad-spectrum
      endectocide for cattle and is suitable for topical delivery.

PMID- 9024868
TI  - Attenuation of Eimeria caviae by selection for precocious development.
AB  - An attenuated line of Eimeria caviae was produced by selection for early
      maturation of oocysts during serial passage in guinea pigs. The prepatent period
      of the parasite was reduced from 11 to 6 days. Parasites of the precocious line
      and the parent strain were found in the crypts of the epithelial cells of caecum
      and colon and were morphologically indistinguishable. The period of development
      of type I, type II and type III merozoites of the E. caviae precocious line in
      guinea pigs was similar to that of the parent strain until the 3rd day. The time
      of the transition from gametocytes to oocysts was 2 days in both the precocious
      line and the parent strain. The maximum number of oocysts per gram of faeces and
      the pathogenicity of the precocious line were less than those of the parent
      strain.

PMID- 9024869
TI  - Trypanosoma cruzi: the major cysteinyl proteinase (cruzipain) is a relevant
      immunogen of parasite acidic antigens (FIII).
AB  - This study examined the immune responses induced by cruzipain, a well
      characterized T. cruzi antigen, to determine whether it is a relevant immunogen
      among the parasite acidic antigens (FIII), for which some biological properties
      have been studied previously. Humoral and cellular immune responses were
      investigated in BALB/C mice after immunization with cruzipain or FIII. Skin tests
      revealed immediate type-hypersensitivity (ITH) and delayed-type hypersensitivity
      (DTH) reactions to cruzipain in both groups of immunized mice. IgG1 and IgE
      isotypes against cruzipain were detected by ELISA in both groups and immunoblot
      studies showed that these antibodies recognized a major protein band of 50 kDa,
      cruzipain. The antigen-specific proliferative responses of spleen lymphocytes
      from both groups of immunized mice were also increased. Immunization with
      cruzipain of FIII antigen significantly enhanced the percentage survival of mice
      challenged with 10(3) trypomastigotes. The results revealed high cross-reactivity
      between cruzipain and FIII, suggesting the cruzipain is a relevant immunogen
      among the parasite acidic antigens.

PMID- 9024870
TI  - Babesia bovis: biosynthesis and localisation of 12D3 antigen in bovine
      erythrocytes.
AB  - The 12D3 antigen of Babesia bovis was found to be synthesised rapidly in cultured
      parasites, and localised to both the apical complex of the merozoite and the
      cytoplasm of the parasitised erythrocyte. Amino-terminal sequencing suggested
      that the nascent protein had been processed and differences between the predicted
      and measured molecular weights suggested post-translational modification. The
      major proportion of 12D3 appeared in the soluble compartment of the parasitised
      erythrocytes with a molecular weight consistent with no further processing. A
      significant proportion of the protein required extraction by sodium carbonate,
      suggesting association with membranous components. The timing of release of
      soluble 12D3 was coincident with haemoglobin release and this probably reflects a
      non-specific lysis of the erythrocyte. Synthesis of recombinant BV12D3 was
      achieved in baculovirus-infected SF9 insect epithelial cells. The product was of
      the same molecular weight as the native 12D3 and polyclonal antibodies raised
      against the recombinant protein reacted with both the recombinant and native
      forms of the antigen.

PMID- 9024871
TI  - Transmission of hydatid disease to sheep from wild dogs in Victoria, Australia.
AB  - Adult tapeworms and metacestodes of Echinococcus granulosus were found commonly
      in wildlife on Crown Land (Alpine National Park or State Forest) in the area
      around Mansfield, Victoria. A total of 756 sheep from 32 farms in the areas were
      examined at slaughter. Seventeen of the farms (Group A) adjoined Crown Land and
      wild dogs commonly entered these farms and killed sheep. A high prevalence of
      hydatid infection was found in sheep from 15 of these farms. Serology and
      arecoline purging failed to identify infection with E. granulosus in any domestic
      dogs on these farms, despite some farmers sometimes feeding their dogs with offal
      of sheep and/or kangaroos. The remaining 15 farms (Group B) were in an area where
      wild dogs did not occur. Sheep infected with hydatid cysts were present on 2
      farms in Group B, but E. granulosus infection was not evident in wildlife species
      examined from this area. The only sheepdog to have detectable serum antibodies
      against E. granulosus was a dog from a farm separating the 2 Group B farms where
      infected sheep were found. Echinococcus granulosus were not found when this dog
      was purged. The implications of the results of this study are discussed in terms
      of transmission and control.

PMID- 9024872
TI  - Time course of coproantigen excretion in Echinococcus multilocularis infections
      in foxes and an alternative definitive host, golden hamsters.
AB  - Coproantigen excretion during experimental infections of Echinococcus
      multilocularis in foxes and an alternative definitive host, golden hamsters, was
      evaluated by a sandwich ELISA using a monoclonal antibody. A sigmoidal increase
      of antigen excretion from the developing parasites was observed in in vitro
      incubation of the parasites collected on different days during the first 21 days
      post-infection (DPI). In hamsters, the ELISA O.D. value of faeces became positive
      at 4 DPI. Thereafter, the O.D. value increased in semi-sigmoidal fashion in the
      first 42 DPI, probably reflecting the development of the parasites. In foxes, the
      O.D. value became positive at 6 DPI. However, contrary to that in hamsters, after
      the initial steep rise, the O.D. value suddenly decreased to 1/2 the level during
      15-17 DPI, indicating that a large number of worms might have been expelled. The
      parasite eggs were detected by the sugar centrifugal-flotation technique (Ito,
      Yagi & Ishige, 1989) from 29 to 84 DPI but not thereafter to 125 DPI, although
      mature parasites were detected at 125 DPI. In contrast, positive O.D. values were
      obtained almost constantly until 125 DPI, indicating that the coproantigen
      detection assay was more sensitive than the egg detection assay. The detection
      limit of the coproantigen assay was roughly estimated to be around 100 worms.
      These observations, along with the fact that the assay was designed to detect a
      heat-resistant coproantigen in heat-sterilized fecal samples, indicate that the
      coproantigen detection assay is a safe and useful method, not only for diagnosis
      in the definitive host of E. multilocularis, but also for monitoring parasite
      development and change in parasite burden during an experimental infection.

PMID- 9024873
TI  - Studies on the host-parasite relationship between Trichostrongylus colubriformis
      and susceptible and resistant sheep.
AB  - This study examined whether infective larvae (L3) of Trichostrongylus
      colubriformis could establish throughout the small intestine and were not
      restricted to the anterior duodenum in susceptible and resistant sheep. The
      location of worms was similar in susceptible animals given doses of T.
      colubriformis between 10,000 and 80,00 T. colubriformis larvae, with 90% of worms
      located in the proximal 3 m of the small intestine. Those worms recovered from
      resistant sheep were also found in the first 9 m of the intestine. However, worms
      recovered from immune sheep were significantly (P = 0.0074) relocated posteriorly
      from the first 3 m into the next 6 m of the intestine. By the surgical
      introduction of worms, it was found that T. colubriformis could establish at any
      site in the small intestine and to some extent in the caecum. Immunity was
      generated principally in the site of predilection in the anterior 3 m of the
      small intestine and effectively expelled challenges given at distal sites and
      caecum, indicating dissemination of immunity throughout the gastrointestinal
      tract. Moreover, the rejection episode had removed worms from the entire small
      intestine within 2 h of introduction through the pylorus.

PMID- 9024874
TI  - Worm kinetics and serum IgE in hooded lister rats infected with the
      acanthocephalan Moniliformis moniliformis and the nematode Nippostrongylus
      brasiliensis.
AB  - After infection with the intestinal helminths Moniliformis moniliformis or
      Nippostrongylus brasiliensis, worm-specific IgE first appeared in the serum rats
      between days 10 and 24 p.i., varying with host age, worm species and worm dose
      used. The rate of increase in specific IgE was comparable regardless of the worm
      species, infection dose or host age and a peak response was observed about 1
      month after the sera turned positive. In the M. moniliformis infections, these
      events took place long before the beginning of worm expulsion on day 63 in high
      dose (50 worms) infections, and potentiation of heterologous IgE was not
      observed. In contrast, IgE stimulation by N. brasiliensis infections was detected
      as potentiation of anti-ovalbumin IgE, anti-M. moniliformis IgE and total IgE.
      Most of the total IgE in the serum of M. moniliformis-infected rats was likely to
      be the worm-specific IgE. Anthelminthic removal of M. moniliformis revealed that
      the presence of residual worms was necessary to maintain worm-specific IgE
      production.

PMID- 9024876
TI  - Recognition of low molecular weight Cooperia oncophora antigens after primary and
      trickle infection of calves with third-stage infective larvae.
AB  - Recognition of low molecular protein fragments of adult Cooperia oncophora of
      calves was studied using sera obtained after a single oral (primary) infection
      with 100,000 infective 3rd-stage C. oncophora larvae, and after a 10-week period
      of trickle infection with moderate doses of these larvae. SDS-gel electrophoresis
      under reducing conditions, followed by western blotting, revealed that a complex
      of 14-16 kDa protein fragments, a 27 kDa and a 31.6 kDa band of Cooperia
      oncophora adult antigen were recognized by sera from calves both after primary
      and trickle infection. A 19 kDa and 30 kDa protein fragment were additionally
      bound by sera from calves after trickle infection. The data suggest that the
      systemic humoral immune response of calves to Cooperia oncophora after trickle
      infection is more pronounced (14-16, 27, 31.6 kDa) and extended (19, 30 kDa) than
      after primary infection with Cooperia.

PMID- 9024875
TI  - The response of breeding doses to nematodiasis: segregation into "responders" and
      "non-responders".
AB  - Responder and non-responder does were identified from a flock of 95 Scottish
      cashmere 2-6 year-old does exposed to natural nematode infection over a 12-month
      period. Every 5 weeks, the does were faecal sampled for worm-egg counts prior to
      anthelmintic treatment. Responsive and non-responsive individuals were identified
      on the basis of their cumulative faecal egg count (FEC) rankings: the 8 lowest
      and 8 highest rankings were deemed to be responders and non-responders,
      respectively. Retrospective analysis showed that the mean egg count of the 8
      responders was significantly lower than that of the 8 non-responders. The
      selected responders and non-responders were subsequently housed together with 8
      randomly selected does from a control line, and given a mixed trickle challenge
      with Teladorsagia circumcincta and Trichostrongylus vitrinus larvae (L3). Mean
      responders FEC was significantly lower following artificial infection than that
      of non-responder and unselected does. Peripheral eosinophilia was significantly
      greater in responders in the first 3 weeks of this infection. On day 60, the
      infection was terminated with anthelmintic and 7 days later the goats were given
      a single challenge of 50,000 T. circumcincta L3. The mean responder worm burden
      was lower, and exhibited greater evidence of retardation of worm development,
      than those of non-responder and unselected does. Responders had significantly
      more mast cells and globule leukocytes post-challenge than did the other 2
      groups. These results suggest that under the conditions encountered in this
      experiment, it is possible to segregate goats into responders and non-responders
      using simple parasitological criteria, as individual responsiveness is a
      relatively repeatable phenomenon.

PMID- 9024877
TI  - Helminth growth in vertebrate hosts: does host sex matter?
AB  - Helminth infections are usually more severe in male than in female vertebrate
      hosts. If parasite establishment is easier in male hosts, parasite growth may
      also be facilitated in males. This was tested with a meta-analysis of published
      between growth rates of worms in male and female vertebrate hosts. Two-thirds of
      the 48 comparisons found showed higher growth in male hosts than in females, but
      the average relative difference did not differ from zero. However, after
      controlling for sample size and for the variability in the original data, a small
      but significant effect of host sex was found. The meta-analysis suggests that
      male hosts harbour not only more helminths than females, but also slightly larger
      ones.

PMID- 9024878
TI  - The suitability of Trochoidea seetzenii of different ages as snail intermediate
      hosts of Muellerius cf. capillaris (Nematoda:Protostrongylidae).
AB  - Larval development of Muellerius cf. capillaris in small (1st-year juveniles,
      shell diameter 0.96 +/- 0.05 cm) and medium-size (2nd-year juveniles, 1.27 +/-
      0.06 cm) Trochoidea seetzenii land snails was significantly more rapid than in
      large adult snails (1.96 +/- 0.09 cm). Only 9% of the inoculated 1st-stage larvae
      (400 +/- 20 per snail) were recovered from the large snails as compared to 25%
      from the medium and small snails. Of the exposed small snails, however, only 35%
      survived to the end of the experiment (33 days post-infection) as compared to a
      97.5% and 98% survival rates for the same period in the medium and large adult
      snails, respectively.

PMID- 9024879
TI  - Depression of the N-demethylation of erythromycin, azithromycin, clarithromycin
      and clindamycin in murine Toxoplasma infection.
AB  - The N-demethylation of macrolides was studied in a murine model of infection.
      Mice were infected with a cystogenic strain of Toxoplasma gondii (20 or 40
      cysts/mouse) and microsomes were prepared from liver homogenates and jejunum
      villus tip enterocytes on day 10 post-infection. The rate of N-demethylation of
      the anti-Toxoplasma macrolides azithromycin, clarithromycin and clindamycin was
      investigated and compared to that of the macrolide erythromycin, a marker of
      activity of the cytochrome P-450 3A (CYP3A) mono-oxygenases. In infected mice (20
      cysts/mouse), the rate of N-demethylation fell in the liver and jejunum for
      erythromycin (-25% and -35%, respectively), azithromycin (-12% and -10%,
      respectively), clarithromycin (-23% and -21%, respectively) and clindamycin (-20%
      and -28%, respectively). The degree of hepatic depression was more marked in mice
      receiving a 40-cysts burden: for erythromycin (-54%), azithromycin (-29%),
      clarithromycin (-49%) and clindamycin (-47%).

PMID- 9024880
TI  - Chloroquine bioassay of plasma specimens obtained from soldiers on chloroquine
      plus doxycycline for malaria prophylaxis.
AB  - In this study we describe the application of a bioassay for measuring chloroquine
      equivalent concentrations in plasma samples obtained from soldiers on chloroquine
      (300 mg weekly) and doxycycline (50 or 100 mg daily) for malaria prophylaxis.
      Chloroquine, its principal metabolite monodesethylchloroquine and doxycycline
      were also measured by high performance liquid chromatography (HPLC).
      Physiological concentrations of doxycycline did not interfere with the
      measurement of chloroquine equivalent concentrations. The correlation between
      bioassay and HPLC was rs = 0.88, with a median bioassay/HPLC chloroquine
      concentration ration of 1.1 (range 0.6-2.4, n = 26). The bioassay is a valuable
      method, particularly under field conditions, for measuring chloroquine
      concentrations and can be very helpful in distinguishing drug failures from
      either poor compliance or inadequate drug absorption.

PMID- 9024882
TI  - The use of ultrasound to study the prevalence of hydatid cysts in the right lung
      and liver of sheep and goats in Turkana, Kenya.
AB  - Ultrasound examination of the liver and right lung was performed in 260 sheep and
      320 goats from the Turkana district of Kenya. Hydatid cysts were visualized in
      9.2% of the sheep and 2.5% of the goats. Of the animals positive on ultrasound,
      87.5% received post-mortem examinations. Eighteen (6.9%) sheep and 5 (1.5%) goats
      were positive for hydatid cysts on ultrasound and post-mortem examination. False
      positives were a result of Taenia hydatigena cysticerci present in the liver in
      all but 1 case. Positive predictive value of ultrasound for diagnosis of
      hydatidosis in sheep and goats was 82.1%.

PMID- 9024881
TI  - A survey for Cryptosporidium spp. in mammals at the Barcelona Zoo.
AB  - Mammals housed at the Barcelona Zoo belonging to the orders Carnivora,
      Artiodactyla, Perissodactyla and Proboscidea were examined for Cryptosporidium
      infections. A total of 183 fecal samples from 17 carnivores and 34 herbivores
      revealed patent infections in only 6 herbivore species (5 artiodactyls of the
      families Bovidae and Giraffidae and 1 perissodactyl of the family
      Rhinocerotidae); all carnivores were negative. Intensity of infection was found
      to be generally low. Connochaetes taurinus taurinus, Gazella dorcas neglecta,
      Kobus ellipsiprymmus and Giraffa camelopardalis constitute new host species for
      the parasite.

PMID- 9024883
TI  - Do haematophagous parasites secrete SOD and promote blood flow?

PMID- 9024884
TI  - The history of the cattle tick Boophilus microplus in Australia and achievements
      in its control.
AB  - For more than 100 years, tick fever and the cattle tick have caused tremendous
      financial loss to cattle producers around the world. Since Australia became
      infected with the disease and infested with its tick vector in the mid-19th
      century, a great deal of research effort has been directed towards their
      effective control by Australian farmers, administrators and scientists. Such
      research has yielded information which has facilitated the development of various
      control strategies that have equal application in other countries afflicted with
      the same problem. It has been demonstrated that integration of a variety of these
      strategies is necessary for long-lasting control.

PMID- 9024885
TI  - Cholinergic, serotoninergic and peptidergic components of the nervous system of
      Discocotyle sagittata (Monogenea:Polyopisthocotylea).
AB  - Cholinergic, serotoninergic (5-HT) and peptidergic neuronal pathways have been
      demonstrated in both central and peripheral nervous systems of adult Discocotyle
      sagittata, using enzyme histochemistry and indirect immunocytochemistry in
      conjunction with confocal scanning laser microscopy. Antisera to 2 native
      flatworm neuropeptides, neuropeptide F and the FMRFamide-related peptide (FaRP),
      GNFFRFamide, were employed to detect peptide immunoreactivity. The CNS is
      composed of paired cerebral ganglia and connecting dorsal commissure, together
      with several paired longitudinal nerve cords. The main longitudinal nerve cords
      (lateral, ventral and dorsal) are interconnected at intervals by a series of
      annular cross-connectives, producing a ladder-like arrangement typical of the
      platyhelminth nervous system. At the level of the haptor, the ventral cords
      provide nerve roots which innervate each of the 9 clamps. Cholinergic and
      peptidergic neuronal organisation was similar, but distinct from that of the
      serotoninergic components. The PNS and reproductive system are predominantly
      innervated by peptidergic neurones.

PMID- 9024886
TI  - Kinetic disposition of an aqueous formulation of alphacypermethrin applied to the
      dorsal mid-line of sheep with long wool and its effect on lice.
AB  - A group of 5 adult Merino sheep with fleeces about 70 mm long (7-months growth of
      wool) was treated with a topical formulation of the synthetic pyrethroid
      insecticide, alphacypermethrin, applied to the dorsal mid-line. Insecticide
      concentrations at the tip, middle and base of wool staples collected from
      meridians along the back, upper and lower flanks were measured at intervals from
      1 to 98 days after treatment. Some movement of the alphacypermethrin from the
      back to the lower body occurred within 24h after treatment, but despite careful
      application of the insecticide there was wide variation in the concentration
      between and within meridians. The majority of the alphacypermethrin remained
      close to the dorsal mid-line and near the tip of the staple. There were
      significant differences in the concentration between the tip, middle and base
      segments of the staples in the back and lower flank meridians (P < 0.05). Despite
      exposure of the sheep to normal weathering, there was no significant difference
      in the concentration of alphacypermethrin between samples collected at day 1 or
      day 98 after treatment (P > 0.05). Numbers of pyrethroid-susceptible lice
      surviving exposure in vitro for 20 h differed significantly between samples
      collected at different times after treatment, lice survived for 20 h in wool
      taken from parts of the fleece that contained high (P < 0.05). The numbers of
      lice surviving in samples collected within 28 days after treatment tended to be
      lower than in those collected from 28 to 98 days but, in some samples, regardless
      of time after treatment, concentrations of alphacypermethrin.

PMID- 9024887
TI  - The kinetic disposition of pyrantel citrate and pamoate and their efficacy
      against pyrantel-resistant Oesophagostomum dentatum in pigs.
AB  - The pharmacokinetic disposition of pyrantel after intravenous (i.v.) and oral
      (p.o.) administration as the citrate and p.o. administration as the pamoate salt
      was determined in pigs. Following i.v. administration pyrantel was quickly
      cleared from the bloodstream, exhibiting a terminal half-life of 1.75 +/- 0.19 h
      and a residence time (MRT) of 2.54 +/- 0.27 h. After p.o. administration as the
      citrate salt, the absorption time (MAT) of pyrantel was 2.38 +/- 0.25 h and
      although significant quantities of pyrantel were absorbed (mean bioavailability
      of 41%) the rapid clearance resulted in a MRT of only 4.92 +/- 0.36 h. By
      comparison, the significantly extended MAT of the less soluble pamoate salt
      resulted in reduced circulating concentrations and a significantly lower mean
      bioavailability of 16%. The poor efficacy of pyrantel citrate against nematodes
      inhabiting the large intestine of pigs is therefore suggested to result from
      insufficient quantities of drug passaging to the site of infection. When tested
      against pyrantel-resistant adult Oesophagostomum dentatum the mean efficacy of
      pyrantel citrate was only 23%, whereas the efficacy of the lesser absorbed
      pyrantel pamoate was 75%. These results indicate that for maximum activity
      pyrantel should be administered to pigs as the pamoate salt.

PMID- 9024888
TI  - Helminth infracommunities in Litoria genimaculata (Amphibia:Anura) from Birthday
      Creek, an upland rainforest stream in northern Queensland, Australia.
AB  - The helminth fauna of Litoria genimaculata, a rainforest frog from northern
      Queensland, was quantified from 53 adult male frogs collected at monthly
      intervals between April 1990 and March 1991. The helminth fauna of this species
      was depauperate (6 species: Mesocoelium sp., Parapolystoma bulliense,
      Austraplectana sp., Onchocercidae gen. sp., Cosmocerca sp. and an unidentified
      nematode larva). The most commonly encountered species was P. bulliense, but the
      intestinal infracommunity was dominated by the digenean Mesocoelium sp. Fifty
      five per cent of frogs were infected with only 1 helminth species and only 1 frog
      had more than 2 species, resulting in low diversity values. These results support
      previous studies which indicate that amphibians have depauperate helminth
      communities.

PMID- 9024889
TI  - The distribution and abundance of Lernaeocera lusci (Copepoda) on hake
      (Merluccius merluccius) and bib (Trisopterus luscus) (Teleostei).
AB  - Distribution patterns, mean intensity and prevalence of Lernaeocera lusci
      (Copepoda, Pennellidae) in its hosts Trisopterus luscus (Teleostei, Gadidae) and
      Merluccius merluccius (Teleostei Merlucciidae) were examined, together with
      parasitic abundance and aggregation in relation to the size of the host. The mean
      parasite abundance and variance to mean abundance ratio increased with host size,
      suggesting that the accumulation of this parasite had no noticeable impact on the
      structure of either host population. Merluccius merluccius being a newly
      colonized host in the Mediterranean, these results are discussed in relation to
      current ideas on the evolution of pathogenicity in heterospecific associations.

PMID- 9024890
TI  - Schistosoma mansoni: permanence of modulation of the granulomatous inflammatory
      response in mice cured in the chronic phase.
AB  - Persistence of down regulation of granuloma size was studied in mice chronically
      infected with Schistosoma mansoni and cured by chemotherapy. The animals were
      reinfected at 20-, 50-, 110-, and 140-day intervals after treatment, and
      sacrificed 60 days post-infection. Reinfected animals were able to modulate the
      granulomatous inflammatory response, thus preventing a new acute phase. These
      findings may contribute to the explanation for the decrease of morbidity from
      human schistosomiasis seen in endemic areas following mass treatment.

PMID- 9024891
TI  - Impaired pulmonary gas exchange in ewes naturally infected by small lungworms.
AB  - Respiratory rate and blood gases were studied in 2 groups of ewes: the ewes in
      group 1 (9 ewes) acted as uninfected controls and those in group 2 (6 ewes) were
      infected with small lungworms (Muellerius, Cystocaulus, Protostrongylus and < 1%
      Neostrongylus). The respiratory rate was higher in infected (49 +/- 19 breath min
      1) than in uninfected ewes. (20 +/- 3 breath min-1); it was strongly reduced
      after treatment (49 vs 22) in infected ewes. The partial carbon dioxide arterial
      tension (PCO2), total CO2 and HCO3- were higher (respectively 77 vs 39 mmHg, 38
      vs 23 mmol-1 and 35 vs 23 mmol-1) in infected compared with uninfected ewes,
      whereas arterial pH (7.2 vs 7.4) and partial oxygen tension PO2 were lower (41 vs
      81 mmHg) in infected ewes. Group 2 was treated with fenbendazole (at 15 mg kg-1
      bodyweight) to eliminate small lungworms, and the respiratory rate and blood
      gases were measured 3 weeks after treatment. The values after treatment were
      similar to those in uninfected ewes. It is concluded that heavy infections by
      small lungworms in ewes impairs gas exchange, but that gas exchange improves
      rapidly after treatment.

PMID- 9024892
TI  - Methionine and cysteine metabolism in Fasciola hepatica.
AB  - Radiolabel from the methyl groups of serine and methyltetrahydrofolate was
      readily incorporated into methionine in adult Fasciola hepatica, and a
      substantial proportion of the label from [35S]methionine appeared in cysteine.
      The data suggest that methionine synthesis is via methyltetrahydrofolate
      homocysteine methyltransferase and that there is cysteine synthesis from
      methionine. Cystathionine-beta-synthase and gamma-cystathionase activities were
      demonstrated in homogenates.

PMID- 9024893
TI  - Cytological study of Rubenstrema exasperatum (Trematoda:Omphalometridae).
AB  - Cytological studies on Rubenstrema exasperatum were carried out. The number of
      chromosomes in diploid cells (2n = 16), and the morphological characteristics of
      the karyotype were determined. All the chromosomes (from Nos 2 to 8) had a well
      defined short arm and, in accordance with the Ic values, were determined to be
      meta-submetacentric. Polymorphism was established in the length of the 2
      homologues of the 1st chromosome. This pair is probably linked with sex
      determination.

PMID- 9024894
TI  - Strongylus asini (Nematoda, Strongyloidea): genetic relationships with other
      Strongylus species determined by ribosomal DNA.
AB  - Genomic DNA was isolated from adult Strongylus asini collected from zebra. The
      second ribosomal transcribed spacer (ITS-2) was amplified and sequenced using
      polymerase chain reaction (PCR) based techniques. The DNA sequence was compared
      with previously published data for 3 related Strongylus species. A PCR-linked
      restriction fragment length polymorphism method allowed the 4 species to be
      differentiated unequivocally. The ITS-2 sequence of S. asini was found to be more
      similar to those of S. edentatus (87.1%) and S. equinus (95.3%) than to that of S
      vulgaris (73.9%). This result confirms that S. Asini and S vulgaris represent
      separate species and supports the retention of the 4 species within 1 genus.

PMID- 9024895
TI  - Itraconazole and leishmaniasis: a randomised double-blind trial in cutaneous
      disease.
AB  - Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease of the skin.
      Previous open controlled studies with oral itraconazole suggest that it was
      effective for CL in India. Twenty patients with localised CL participated in this
      trial. Patients were allocated randomly to receive capsule itraconazole and
      matching placebo for 6 weeks. No topical medicines were used. Demonstration of
      Leishmania by slit smear was mandatory. Prior to, periodically during and 3
      months after completion of therapy an overall clinical assessment, liver function
      tests and urinalysis were performed. On decoding, out of the 10 cases receiving
      drug itraconazole, 7 were declared cured by clinical and parasitological
      criteria. No major side-effects were noted. Spontaneous remission was observed in
      1 case in the placebo group at 3 months follow up. Oral itraconazole has a
      promising antileishmanial thus secure CL patient from the hazards of antimonials.

PMID- 9024896
TI  - Anaplasma marginale: effect of challenge of cattle with varying doses of infected
      erythrocytes.
AB  - Three groups, each of 6 Hereford cattle, were infected by the i.v. inoculation of
      10(10), 10(8) or 10(6) Anaplasma marginale-infected erythrocytes. The mean time
      taken to reach a 1% parasitaemia was 7.3, 13.9 and 19.9 days in the 10(10),
      10(8)and 10(6) infection dose groups, respectively. The rates of increase in
      parasitaemias during the exponential phase of parasite multiplication were
      similar for the 3 groups (doubling time 0.9 days). The exponential increase of
      the parasitaemia in the 10(10) dose group extended to a higher level or 10(6)
      dose groups (to approximately 10% compared with 3%). The mean maximum
      parasitaemia attained in the 10(10), 10(8), and 10(6) infection dose groups was
      23.7, 14.7 and 8.7%, respectively> The time taken to reach the treatment
      criterion (packed cell volume decrease to 15% or lower) from a 1% parasitaemia
      was similar for the 3 groups. These results showed that the pathological outcome
      (anaemia) of anaplasmosis were similar over the 10,000-fold infective dose range
      tested.

PMID- 9024897
TI  - A comparison of structural relationships among alpha-crystallin, human Hsp27,
      gamma-crystallins and beta B2-crystallin.
AB  - The 3D structures of alpha-crystallin, a major eye lens protein, and related
      small heat shock proteins are unresolved. It has been assumed that alpha
      crystallin is primarily a beta-sheet globular protein similar to alpha-crystallin
      (Siezen and Argos, Biochim. Biophys. Acta, 1983, 748, 56-67) containing sequence
      repeats in its two domains (Wistow, FEBS Lett. 1985, 181, 1-6). Positional
      flexibility of amino acid residues and far UV-circular dichroism spectroscopy
      were used to investigate structural relationships among these proteins. The
      utility of flexibility plots for predicting protein structure is demonstrated by
      the excellent correlation of these plots with the known 3D X-ray structures of
      beta/gamma-crystallins. Similar analyses of alpha-crystallin subunits, alpha A
      and alpha B, and human heat shock protein 27 show that the C-terminal domains and
      connecting segments of these proteins are very similar while the N-terminal
      domains have significant structural differences. Unlike beta/gamma-crystallins,
      both Hsp27 and alpha-crystallin subunits are asymmetrical with highly flexible C
      terminal domains. Flexibility is considered essential for protein functional
      activity. Therefore, the C-terminal region may play an active role in alpha
      crystallin and small heat shock protein function. Differences in flexibility
      profiles and estimated secondary structure distribution in alpha-crystallin by
      three recent/updated algorithms from far UV-CD spectra support our predicted 3D
      structure and the concept that alpha-crystallin and members of beta/gamma
      superfamily are structurally dissimilar.

PMID- 9024898
TI  - Destabilisation of native tertiary structural interactions is linked to helix
      induction by 2,2,2-trifluoroethanol in proteins.
AB  - The effect of 2,2,2-trifluoroethanol (TFE) on the structure of an all beta-sheet
      protein, cardiotoxin analogue 111 (CTX III) from the Taiwan cobra (Naja naja
      atra) is studied. It is found that high concentrations (> 80% v/v) of TFE induced
      a beta-sheet to alpha-helix structural transition. It is found that in denatured
      and reduced CTX III (rCTX III) helical conformation is induced even upon addition
      of low concentrations (> 10% v/v) of TFE. Using three other proteins, namely,
      ribonuclease A (RNase A), lysozyme and alpha-lactalbumin, it is been observed
      that helix-induction by TFE is intricately linked to drastic destabilization of
      native tertiary structural interactions in the proteins.

PMID- 9024899
TI  - Differential scanning calorimetric studies on bovine serum albumin. IV. Effect of
      anionic surfactants with various lengths of hydrocarbon chain.
AB  - Using defatted and SH-blocked bovine serum albumin (BSA), measurements of
      differential scanning calorimetry (DSC) have been made at pH 7 on the complexes
      of BSA and a series of sodium alkyl sulfates used were sodium decyl sulfate
      (SDeS), sodium octyl sulfate (SOS), sodium hexyl sulfate (SHS) and sodium ethyl
      sulfate (SES). Results obtained were compared with those on the system BSA-sodium
      dodecyl sulfate (SDS) studied previously. Two peaks P1 and P2 existed in the DSC
      curve of BSA. These peaks originate in the heat-induced transition of BSA. The
      pattern of DSC curve changed with the amount of the ligand added, i.e. with the
      molar mixing ratio ligand/BSA (1). The change for systems BSA-SDeS, BSA-SOS and
      BSA-SHS was qualitatively the same as that for the system BSA-SDS (2).
      Interestingly, SES, which is not a surfactant, interacts with BSA. The change for
      the system BSA-SES was qualitatively the same as that for the system BSA-Na2SO4.
      All alkyl sulfates suppressed the heat-induced transition at lower
      concentrations. A linear relationship was obtained for the plots of log(D/A)1
      versus log CMC, where (D/A)1 is the molar mixing ratio of anionic surfactant (D)
      to BSA (A) at which the most heat-stable complex is formed. This suggests that
      the hydrophobic force has a serious effect on the formation of heat-stable
      complexes.

PMID- 9024900
TI  - Adjustable 'cross-linking' of neighboring DNA molecules in liquid-crystalline
      dispersions through (daunomycin-copper) polymeric chelate complexes.
AB  - The interaction of daunomycin molecules with double-stranded DNA in the liquid
      crystalline state was investigated. It was shown that at a certain extent of
      daunomycin binding a change of the mechanism of anthracycline orientation with
      reference to the DNA chain occurs. This is testified by the alteration of the
      sense of spatial packing of the DNA molecules in liquid-crystalline dispersions
      formed as a result of phase separation in poly(ethyleneglycol)-containing
      solutions, as well as by the onset of the reaction of daunomycin with divalent
      copper ions. Using this reaction, polymeric (daunomycin-copper) chelate cross
      links between the DNA molecules fixed in the liquid-crystalline dispersions were
      formed. The length of such cross-links as adjusted by the distance between the
      DNA molecules, which, in turn, depends on the concentration of
      poly(ethyleneglycol) used for phase separation. The above molecular building
      mechanism may lead to new interesting applications.

PMID- 9024901
TI  - Kinetics of inactivation of green crab (Scylla Serrata) alkaline phosphatase
      during removal of zinc ions by ethylenediaminetetraacetic acid disodium.
AB  - Green crab (Scylla Serrata) alkaline phosphatase (EC 3.1.3.1) is a metalloenzyme,
      the each active site in which contains a tight cluster of two zinc ions and one
      magnesium ion. The kinetic theory of the substrate reaction during irreversible
      inhibition of enzyme activity previously described by Tsou has been applied to a
      study on the kinetics of the course of inactivation of the enzyme by
      ethylenediaminetetraacetic acid disodium (EDTA). The kinetics of the substrate
      reaction with different concentrations of the substrate p-nitrophenyl phosphate
      (PNPP) and inactivator EDTA suggested a complexing mechanism for inactivation by,
      and substrate competition with, EDTA at the active site. The inactivation
      kinetics are single phasic, showing the initial formation of an enzyme-EDTA
      complex is a relatively rapid reaction, followed a slow inactivation step that
      probably involves a conformational change of the enzyme. Zinc ions are finally
      removed from the enzyme. The presence of metal ions apparently stabilizes an
      active-site conformation required for enzyme activity.

PMID- 9024903
TI  - Thermal denaturation and gelation of rubisco: effects of pH and ions.
AB  - In order to understand the mechanism of thermal gelation of rubisco, its native
      and heat denatured states were characterized by absorbance, fluorescence and
      circular dichroism spectroscopies as well as by differential scanning calorimetry
      in the presence of various salts. It appears that during the denaturation
      process, divalent anions are released while divalent cations are fixed by the
      protein, while it is disorganized and while the environment of its aromatic
      chromophores becomes more hydrophilic. The pH transition of gelation is shifted 1
      2 pH units higher than the transition of denaturation temperature which occurs
      near the isoelectric point of the native molecule. This shift probably
      corresponds to the breaking of saline bridges within the protein molecule.
      Finally, a large effect of divalent cations on the phase diagram indicates that a
      particular denatured state is attained when these cations are in the denaturation
      medium.

PMID- 9024902
TI  - Polyelectrolyte/amphiphile interaction studied by surface tension measurements.
AB  - The interaction of kappa-carrageenan with three positively charged drug molecules
      with amphiphile character has been examined using surface tension measurements.
      The surface tension was measured by the pendant drop method which makes possible
      the determination at an apparent steady state which is important for polymeric
      systems. The results are compared with adsorption isotherms from dialysis
      equilibrium. The surface tension data, show that the presence of kappa
      carrageenan in the amphiphile solutions leads to an increased and pronounced
      lowering of the surface tension in a low concentration range of amphiphile. It is
      also shown that not only the hydrophobicity of the amphiphile but also the
      structure of the polyelectrolyte (charge density and helix-coil structure)
      largely determine the extent of interaction.

PMID- 9024904
TI  - On the importance of van der Waals interaction in the groove binding of DNA with
      ligands: restrained molecular dynamics study.
AB  - Comparison of interaction energy between an oligonucleotide and a DNA-binding
      ligand in the minor and major groove modes was made by use of restrained
      molecular dynamics. Distortion in DNA was found for the major groove mode whereas
      less significant changes for both ligand and DNA were detected for the minor
      groove binding after molecular dynamics simulation. The conformation of the
      ligand obtained from the major groove modes resembles that computed with the
      ligand soaked in water. The van der Waals contact energy was found to be as
      significant as electrostatic energy and more important for difference in binding
      energy between these two binding modes. The importance of van der Waals force in
      groove binding was supported by computations on the complex formed by the
      repressor peptide fragment from the bacteriophage 434 and its operator
      oligonucleotide.

PMID- 9024905
TI  - The step-size distance in muscle contraction: properties and estimates.
AB  - The step-size distance in muscle contraction is obtained using the step-size
      distance equation z = u/n, where z is the step-size distance, u is the actin
      filament velocity and n is the ATPase rate of splitting. In a previous study a
      step-size distance of about 17 A at no load was determined for intact frog
      muscle. Some properties of the step-size equation are described. We have now made
      estimates of the step-size distance z for a variety of muscles using existing
      physiological and biochemical data in the literature. The estimates are listed in
      Tables 1 and 2. We find that the step-size distances are clustered in the range
      13-17 A for nearly all muscles.

PMID- 9024906
TI  - How to do a simple epidemiological study. II. Practice.

PMID- 9024907
TI  - Coronary artery aneurysmal fistula: a late complication of stent deployment.
AB  - An unusual case of a coronary artery fistula with the right atrium is described.
      Four months following the placement of a stent in a high grade, complex lesion of
      the proximal right coronary artery, restenosis, and contrast spill with rapid
      clearance into the right atrial space was evident on coronary angiogram. The
      calculated shunt fraction was trivial and hemodynamically insignificant.

PMID- 9024908
TI  - The nature of the cardiac myxoma.
AB  - Ten archive cases of cardiac myxoma were evaluated for proliferative activity,
      metastatic potential and expression of oncogene/tumor suppressor gene products by
      means of PCNA, MIB1, nm23, p53, Bcl-2 and Rb-1 immunohistochemistry. The myxomas
      showed variable proliferative activity (PCNA 0-41%, average 12.6%, MIB1 0-13%,
      average 3.2%) contrasting with the absence of mitotic activity histologically.
      All the myxomas showed nm23 staining. None showed p53 reactivity. Eight cases
      were negative for Bcl-2 expression, with two cases giving weak cytoplasmic
      staining. Rb-1 reactivity showed a variable pattern (staining indices 0-86%)
      paralleling the cases' proliferative activity. The cardiac myxoma is interpreted
      as a weakly proliferative lesion with little metastatic potential and no
      modulation of oncogene/oncogene suppressor products. Whilst not excluding a
      neoplastic aetiology, the results are considered more in keeping with a
      reactive/hamartomatous process.

PMID- 9024909
TI  - Regression of left ventricular dilatation and hypertrophy after aortic valve
      replacement.
AB  - The aim of the study was to assess the influence of aortic valve replacement on
      left ventricular size and muscle hypertrophy according to the type of preexisting
      valve disease (aortic stenosis, insufficiency or combined disease). The study
      group consisted of 143 consecutive patients (pts) after aortic valve replacement
      (109 men, 34 women, mean age 48.1 +/- 10.9 years). Reason for the operation was
      aortic stenosis in 35 pts, aortic insufficiency in 64 pts and combined disease in
      44 pts. Echocardiography was performed before surgery, 1 month and 1 year after
      operation, and yearly during 5-year follow-up. Transvalvular aortic pressure
      gradients decreased significantly after valve replacement in all subsets without
      further changes during follow-up (Pmax (mmHg): from 54.2 +/- 20.7 to 17.9 +/- 9.6
      in combined disease pts, from 72.3 +/- 19.9 to 21.6 +/- 14.6 in aortic stenosis
      and from 34.5 +/- 24.2 to 15.6 +/- 11.3 in aortic insufficiency pts,
      respectively, P < 0.0005). One year after surgery the diastolic dimension of the
      left ventricle decreased significantly in all subjects, whereas the systolic
      dimension only in aortic insufficiency and combined disease pts (from 44 +/- 11.8
      to 31.6 +/- 5.4 mm, P < 0.001 and from 41.9 +/- 11.5 to 33 +/- 6.7 mm, P < 0.05,
      respectively). Further decrease of both diastolic and systolic dimensions was
      observed only in the aortic insufficiency group. Ejection fraction of left
      ventricle increased only in combined disease pts (from 51.6 +/- 10% to 56.8 +/-
      8.2%, P < 0.05). Wall thickness of the left ventricle decreased 1 year after
      valve replacement only in the aortic stenosis group and in further follow-up in
      the aortic stenosis and combined disease group. Normalization of left ventricular
      size is observed in more than 90% of patients during 5-year follow-up as opposed
      to left ventricular muscle hypertrophy, regressed only in less than a half of the
      study population. In patients with aortic valve disease the greatest hemodynamic
      improvement is observed 1 year after valve replacement. This is expressed by
      marked reduction of the left ventricular dimensions and wall thickness, without
      significant improvement of the ejection fraction. Further regression of left
      ventricle dimensions occurs in patients operated on due to predominant valve
      insufficiency, whereas regression of left ventricular hypertrophy is observed in
      patients with preexisting valvular stenosis.

PMID- 9024910
TI  - Myocardial infarction postpartum in patients taking bromocriptine for the
      prevention of breast engorgement.
AB  - Three cases of myocardial infarction (MI) in women taking bromocriptine for milk
      suppression are presented. The incidents occurred in 1993 and 1994, the last only
      two weeks before the withdrawal of the drug from the American market as a drug
      suitable for ablactation. In one patient, the MI presented on the 12 day
      postpartum and was accompanied by signs and symptoms reminiscent to ergotism.
      Another mother suffered MI, accompanied by hypertension, six days after a vaginal
      delivery complicated by postpartum haemorrhage. The third patient began to take
      bromocriptine more than 2 weeks postpartum and died suddenly 24 days after her
      childbirth. To the knowledge of the authors, these are the 12th to 14th literary
      reports describing an apparent association between the use of bromocriptine for
      ablactation and the occurrence of MI in the puerperium.

PMID- 9024911
TI  - Breathlessness and exercise capacity in heart failure: the role of bronchial
      obstruction and responsiveness.
AB  - The cause of the breathlessness and reduced exercise capacity that occur in
      patients with chronic heart failure remains obscure. We examined the hypothesis
      that airway obstruction and bronchial hyper-responsiveness, which are recognised
      features of chronic heart failure, might contribute to the breathlessness and
      reduced exercise capacity in this condition. We studied 37 patients (7 female)
      with chronic heart failure, of mean age 61 years. Each patient underwent: (i)
      lung function testing with spirometry and expiratory flow volume loops. (ii)
      Measurement of bronchial responsiveness to methacholine. (iii) Symptom-limited
      treadmill exercise capacity using both incremental and fixed workload protocols,
      with measurement of Borg scores for breathlessness. Lung function was not
      significantly related to either exercise time, or Borg symptom scores in either
      exercise protocol. Bronchial hyper-responsiveness to methacholine was
      demonstrated in 12 patients. Exercise time did not correlate with the degree of
      bronchial hyper-responsiveness in these 12 patients. Group mean exercise time and
      Borg scores were not significantly different in these 12 patients when compared
      to the 25 patients in whom bronchial hyper-responsiveness was not found. We
      conclude that airway obstruction and bronchial hyper-responsiveness are not
      likely to be important determinants of reduced exercise capacity and
      breathlessness in chronic heart failure.

PMID- 9024912
TI  - Carotid sinus pressure: a new application of an old maneuver. A preliminary
      report.
AB  - This study reveals the capability of carotid sinus pressure (CSP) in
      distinguishing aberrant ventricular complexes from ventricular ectopy in atrial
      fibrillation. Nine patients with atrial fibrillation and frequent (> 10/min)
      single and/or repetitive wide QRS-complexes (duration > 0.12 s) participated.
      None of them were on antiarrhythmic medication, included digitalis. CSP was
      performed during ECG monitoring and the response to it was arbitrarily designated
      positive if it resulted in slowing of the ventricular rate and a temporary
      abolition of wide QRS-complexes. The origin of wide QRS-complexes was verified by
      an i.v. bolus of adenosine and/or lidocaine. Our results showed that CSP resolved
      aberrant beats in 85.7% (six of seven patients) and had high specificity (100%),
      accuracy (88.9%) and predictive value (100%). In conclusion, CSP can be used as a
      simple bedside technique to distinguish the origin of wide QRS-complexes.

PMID- 9024913
TI  - Detection of coronary artery disease in the presence of left ventricular atrophy.
AB  - To evaluate the accuracy of exercise echocardiography for the recognition of
      coronary artery disease in the presence of left ventricular hypertrophy 70
      patients were studied. Significant coronary artery disease was present in 25
      patients and left ventricular hypertrophy had 29 patients. All patients underwent
      an exercise ECG and echocardiographic test during which cine-loop digitized
      echocardiography was obtained. Wall motion was analyzed and a regional wall
      motion score index was calculated. The overall sensitivities of exercise ECG and
      echocardiography for detecting coronary artery disease were 60% and 64%,
      respectively, and the specificities were 49% and 78%, respectively. In patients
      with left ventricular hypertrophy the specificity of exercise echocardiography
      was higher (71%) compared to exercise ECG (21%) while in patients without
      hypertrophy the sensitivity was higher (70% vs. 40%, respectively). Of the 19
      patients with a non-diagnostic stress ECG, echocardiography correctly identified
      100% of those with coronary artery disease but only 53% of those without disease.
      It is concluded that exercise digital echocardiography represents a good
      diagnostic alternative to the exercise ECG for identifying coronary artery
      disease in the presence of left ventricular hypertrophy and should be useful in
      patients with a non-diagnostic exercise ECG.

PMID- 9024914
TI  - Temperature and impedance monitoring during radiofrequency catheter ablation of
      slow AV node pathway in patients with atrioventricular node reentrant
      tachycardia.
AB  - This study was designed to observe the changes of temperature and impedance and
      to find the role of temperature control in radiofrequency ablation of slow
      pathways in patients with AV node reentrant tachycardia. Power, impedance and
      temperature were measured during each application of radiofrequency energy while
      the generator was operated in the power control mode. A total of 760 applications
      were delivered in 76 patients. The success rate was 100% without recurrence
      during a follow-up period of 8 +/- 3 months. The mean catheter tip temperature
      associated with successful ablation was 51.3 +/- 5.4 degrees C (range 45 degrees
      C to 64 degrees C), and significantly higher than the unsuccessful pulses (48.7
      +/- 6.2 degrees C, P < 0.05). The mean temperature was 49.8 +/- 3.1 degrees C
      during accelerated junctional rhythm, significantly higher than the pulses
      without this rhythm. The mean temperature correlated well with early decrease of
      impedance (r = 0.71, P < 0.001), and an early decrease of impedance more than 5
      ohms had an 87% positive predictive value for adequate tissue heating. These data
      suggested that, if temperature monitoring was available, setting the target
      temperature at about 51 degrees C could achieve adequate tissue heating for
      successful ablation of slow pathway; if not, impedance monitoring with an early
      decrease of impedance < 5 ohms could predict adequate tissue heating.

PMID- 9024915
TI  - Correlation of lipoprotein (a) to angiographically defined coronary artery
      disease in Indians.
AB  - Lipoprotein (a) [Lp(a)] levels have been correlated with angiographically defined
      coronary artery disease (CAD). Pattern of Lp(a) distribution in various racial
      groups is different. To study this relationship in Indian patients, plasma levels
      of Lp(a) and other lipid values were assessed in 101 patients undergoing coronary
      arteriography. Lp(a) concentration was higher in CAD group (n = 77) compared to
      normal coronary artery group (n = 24) (26.83 +/- 22.09 mg/dl vs. 15.07 +/- 14.61
      mg/dl, P < 0.05). Lp(a) values had graded association with CAD. In Lp(a) quartile
      of < 5 mg/dl, 66.7% patients had CAD; in Lp(a) quartile of 5-25 mg/dl, 69.0% had
      CAD; Lp(a) quartile of 26-75 mg/dl, 87.5% had CAD; and in Lp(a) quartile of > or
      = 76 mg/dl, all patients had CAD. High density lipoprotein (HDL) cholesterol was
      higher in the normal coronary artery group as compared to CAD group (45.25 +/-
      8.26 mg/dl vs. 41.83 +/- 16.47 mg/dl; NS). In HDL quartile of < 35 mg/l, 88.9%
      patients had angiographically defined CAD. Plasma values of total cholesterol,
      triglycerides (TG), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), low
      density lipoprotein (LDL) cholesterol, LDL/HDL cholesterol ratio and Apo A1/B
      ratio were not significantly different in the groups with normal coronary
      arteries and CAD. Our results indicate that the measurement of Lp(a) provides a
      better marker for predicting the presence of angiographically defined CAD as
      compared to traditional measures.

PMID- 9024917
TI  - Status of chest X-ray in diagnosing right ventricular infarction.
AB  - Right ventricular enlargement on left anterior oblique view at 60 degrees had low
      sensitivity (58.8%) but very high specificity (100 %) for diagnosing right
      ventricular infarction. Right ventricular and right atrial enlargement on other
      views had very low sensitivity (16.7-26.7%) but high specificity (80-90%). Thus
      chest X-ray in left anterior oblique view at 60% is useful in detecting right
      ventricular infarction when clinical examination and electrocardiogram are
      inconclusive.

PMID- 9024916
TI  - Course of impaired left ventricular function after acute myocardial infarction
      predicted with planar thallium-201 chloride and F18-fluorodeoxyglucose imaging.
AB  - Planar reset myocardial thallium-201 chloride (201Tl)/F18-fluorodeoxyglucose
      (FDG) imaging has been shown to distinguish between viable and non-viable tissue.
      Twenty-five patients (60 +/- 9 years) with acute myocardial infarction were
      studied using this technique within 6 +/- 2 days (T1) after infarction and again
      after 42 +/- 4 days (T6). Serial assessment of wall motion with 2D
      echocardiography was performed to determine the predictive value of radionuclide
      indices for the course of impaired regional left ventricular function. No
      revascularization procedure was performed. Segmental 201Tl and FDG uptake was
      evaluated using circumferential profiles. Echocardiographic wall motion was
      scored as normal, hypokinetic or akinetic. Myocardial segments were considered
      non-viable if a match between 201Tl and FDG uptake was present, which is a
      concordant reduction in 201 Tl and FDG uptake (Group A). Myocardial segments were
      considered viable if: a mismatch was present between 201Tl and FDG uptake which
      was defined as a segmental FDG uptake exceeding 201Tl uptake by > or = 20% in a
      segment with reduced 201Tl uptake (Group B); a normal FDG uptake (> or = 75%) was
      present without a mismatch pattern in a segment with reduced 201Tl uptake (201Tl
      < 75% of peak activity) (Group C); a normal 201Tl uptake was present in the area
      of wall motion abnormality (Group D). Corresponding scintigraphic images obtained
      at T1 and T6 were compared. RESULTS: 51 segments were normokinetic, 37 were
      hypokinetic and 6 were akinetic at T1. Of the 63 segments with wall motion
      abnormalities at T1, 18 regions showed a match (FDG-201Tl < 20%) (Group A).
      Regional function improved in only one (6%) of these segments. In 19 regions a
      mismatch was present (FDG-201Tl > 20%) (Group B) of which three (16%) showed
      spontaneous improvement in function (p = NS vs. matched segments), although
      recovery varied considerably among patients. Regional function in two segments
      deteriorated. In 14 regions with reduced 201Tl uptake, FDG uptake was normal
      (Group C) of which five (36%) were improved after 6 weeks (p < 0.05 vs. match; p
      = NS vs. mismatched segments). Of the 12 segments with normal 201Tl uptake (Group
      D), seven (58%) showed improvement in function, whereas five (42%) did not show
      improvement (p < 0.05 vs. match). In addition, all scintigraphically selected
      viable segments were grouped (Group B + C + D) and compared with the non-viable
      segments (Group A). The predictive value of a positive viability test for
      spontaneous functional improvement was 33%. The predictive value of a negative
      viability test for lack of functional improvement was 94%. CONCLUSIONS: absence
      of residual FDG uptake shortly after infarction is associated with irreversible
      injury, while preservation of metabolic activity identifies segments with
      variable outcome. Wall motion alone is not a good indicator for the presence of
      viable tissue. Planar 201Tl/FDG imaging allows early identification of viable but
      jeopardized tissue and may help select patients who will benefit from aggressive
      therapy to salvage endangered myocardium.

PMID- 9024918
TI  - Subaortic stenosis due to accessory tissue of the mitral valve associated with
      Ebstein's anomaly in an adult.
AB  - A 26-year-old man with a history of effort-induced syncopal attacks was found to
      have Ebstein's anomaly. A cardiac catheterization revealed a pressure gradient of
      77 mmHg between the left ventricle outflow tract which was caused by mitral
      accessory tissue. The accessory tissue was resected, the aortic valve was
      replaced, and the Ebstein's anomaly was corrected. The degree of mitral
      regurgitation was seen to increase following surgery. This is the first reported
      case of an accessory mitral valve complicated with Ebstein's anomaly.

PMID- 9024920
TI  - Simultaneous pneumopericardium and pneumoperitoneum late after coronary bypass
      grafting with the gastroepiploic artery.

PMID- 9024919
TI  - Exercise-induced syncope as late consequence of radiotherapy.
AB  - This report describes a 34-year-old female with an exercise-induced
      atrioventricular block resulting from transient ischemia caused by a radiation
      induced ostial stenosis of the right coronary artery. Patient first underwent
      coronary artery surgery with a right internal mammary artery to the right
      coronary artery. After 18 months she was readmitted with exercise-induced syncope
      due to graft occlusion. This time a successful rotablator procedure was performed
      on the ostial stenosis.

PMID- 9024921
TI  - Torsade de pointes in a patient using usual dose of beta agonist therapy.

PMID- 9024922
TI  - The Indian puzzle: may be solved by magnesium.

PMID- 9024923
TI  - Non-invasive, in-vivo electrical impedance of EMT-6 tumours during hyperthermia:
      correlation with morphology and tumour-growth-delay.
AB  - The electrical impedance at frequencies from 100 Hz to 40 MHz of EMT-6 tumours
      was measured non-invasively, in vivo, during hyperthermia using an apparatus
      constructed for this purpose. Histology and morphometry were performed on tumours
      harvested periodically during the heating. A ratio of conductivities at two
      frequencies (sigma (10MHz)/sigma (10kHz)), which minimizes the tissues
      temperature-coefficient effects, was used to correlate impedance changes with the
      histopathological changes. The bulk of the cell population followed a necrotic
      cell death sequence during heating. Initial increase of the sigma-ratio
      correlated with cell swelling, and a reversal of the rate of this increase
      correlated with the appearance of small membrane breaks and evidence of
      mitochondrial damage. A continued, slowing sigma-ratio increase to a maximum
      correlated with continued cell swelling accompanied by increasing membrane
      disruption. The subsequent decrease in sigma-ratio correlated with continued
      general cell lysing. Between the appearance of the first membrane breaks (sigma
      ratio peak) and the evidence of general lysing (sigma-ratio peak), the tumour
      growth-delay increased non-linearly. Because the sigma-ratio consistently
      discerned these events, these measurements were able to predict the fate of this
      cell population when subjected to hyperthermia. Knowledge of temperature or time
      of heating was not required.

PMID- 9024924
TI  - The effects of artery occlusion on temperature homogeneity during hyperthermia in
      rabbit kidneys in vivo.
AB  - To investigate the role of arterial occlusion on temperature homogeneity during
      hyperthermia for deep seated tissue, a renal hyperthermia animal model has been
      established using New Zealand white rabbits. The effects of ultrasound-induced
      renal hyperthermia, with or without continuous and intermittent renal artery
      occlusion, were compared and analysed. Both continuous and intermittent occlusion
      showed certain protection of surrounding tissue and demonstrated improved
      temperature homogeneity and heating efficiency. The benefits of continuous vs.
      intermittent occlusion are compared and discussed as well.

PMID- 9024926
TI  - Influence of tonicity and chloramphenicol on hyperthermic cytotoxicity and cell
      permeability under various heating rates.
AB  - The cell lethality and permeability induced in Escherichia coli B/r, Escherichia
      coli Bs-1 and Zygosaccharomyces bailii cells by high temperature (52 degrees C)
      after heating at different rates (mean s 0.015, 0.25 and 1.50 degrees C per s)
      and in media of different tonicity and content (isotonic YEP broth versus 0.01 M
      phosphate buffer, pH 7.0 containing different concentrations of NaCl) and with
      versus without chloramphenicol (10 micrograms/ml) have been investigated.
      Hyperthermic treatment in YEP broth of isotonic 0.01 M phosphate buffer resulted
      in markedly reduced cytotoxicity with decreasing heat rate. The heating rate
      effect was larger when the cells were treated in YEP broth. Chloramphenicol,
      which is known to inhibit expression of heat shock proteins in bacteria, did not
      affect the viability of cells or the development of thermotolerance in cells
      heated at different heating rates in isotonic phosphate buffer but prevented the
      development of an additional degree of thermotolerance in cells heated slowly in
      YEP broth. In contrast, the differential effect of heating rate on cytotoxicity
      and cell permeability was not demonstrated when cells were heated in hypertonic
      solution (1M NaCl in phosphate buffer, pH 7.0). It is proposed that heat
      destabilization of the osmotic cell homeostasis, which is more profound after
      rapid heating, plays a major part in heat induced cellular lethality.

PMID- 9024925
TI  - Heat shock protein 72 (HSP72), a hyperthermia-inducible immunogenic determinant
      on leukemic K562 and Ewing's sarcoma cells.
AB  - Following non-lethal heat stress (41.8 degrees C) and a recovery period at 37
      degrees C, the inducible 72kDa HSP (HSP72) is detectable selectively on the cell
      surface of human Ewing's Sarcoma (ES) and of leukemic K562 cells but not on EBV
      transformed B cells (B-LCL) which were generated from PBL of healthy human
      volunteers. The HSP72 expression was measured by flowcytometric analysis using a
      monoclonal antibody (moAb) that specifically recognizes HSP72, the inducible form
      of the HSP70 group. The major histocompatibility complex (MHC) class I
      expression, detected with moAb W5/32 was not affected by non-lethal heat exposure
      and a recovery period at 37 degrees C for 12 h: ES cells express MHC class I
      molecules on about 80% of the cells; K562 cells exhibited no MHC class I
      expression neither before nor after heat shock. Inhibition of RNA-(actinomycin D)
      of protein-synthesis (cycloheximide) prior to heat treatment completely inhibits
      the expression of HSP72 on the cell surface of both tumour cells, thus indicating
      that de novo protein synthesis is required for HSP72 cell surface expression.
      Since, apart from HSP72, protein synthesis in general is down-modulated by heat
      shock we speculate that HSP72 molecules that are expressed on the cell surface of
      tumour cells might be recruited from newly synthesized proteins. The heat
      inducible HSP72 cell surface expression on tumour cells could be correlated with
      an increased sensitivity of leukemic and sarcoma cells to lysis mediated by NK
      effector cells. The results of cold target inhibition assays revealed that
      histologically different tumour cells (sarcoma and leukemic cells) that were
      exposed to non-lethal temperatures have to share a similar if not identical HSP72
      immunogenic determinant.

PMID- 9024927
TI  - In vitro effects of hyperthermia combined with cisplatin or peplomycin on the
      human maxillary carcinoma cell line IMC-2.
AB  - We examined the interactive effects of hyperthermia combined with cisplatin
      (CDDP) (0.5 micrograms/ml) or peplomycin (PEP) (1.0 microgram/ml) on surviving
      fractions of human maxillary carcinoma IMC-2 cells. Either CDDP or PEP enhanced
      the 44 degree C thermosensitivity of thermotolerant cells after heating at 42
      degrees C for 2 hours. The development of thermotolerance at 42 degrees C with
      either of the two drugs for 2 hours was not inhibited by CDDP, but it was
      partially inhibited by PEP. Moreover, for PEP throughout the entire period of 42
      44 degrees C step-up heating, the 44 degree C thermosensitivity of thermotolerant
      cells after heating at 42 degrees C with PEP for 2 hours was enhanced similarly
      to that at 44 degrees C with PEP. Heating at 42 degrees C combined with either of
      the two drugs showed a marked interactive effect.

PMID- 9024928
TI  - Heat response of HT29 cells depends strongly on perfusion--a 31P NMR
      spectroscopy, HPLC and cell survival analysis.
AB  - A model system of perfused human colon adenocarcinoma cells (HT29) encapsulated
      in alginate was used to examine metabolic response to heat therapy with 31P NMR
      spectroscopy, HPLC and cell survival analysis. The presented data show, that
      perfused (medium flow during hyperthermia) and non-perfused (no medium flow
      during hyperthermia) cells are very difficult in their sensitivity to
      hyperthermia. Under equivalent experimental conditions with respect to medium pH,
      oxygen and nutrient concentration, encapsulated perfused HT 29 cells display a
      significantly lower thermal sensitivity than non-perfused cells. This reduced
      sensitivity of perfused cells is characterized by an increased cell survival and
      relative ATP concentration, and reduced drop of the NTP/Pi ratio in the long-term
      follow up towards zero. The relative ATP concentration determined by HPLC after
      hyperthermia is correlated with the clonogenic survival fraction. There is a
      direct relationship, depending on the specific experimental conditions (perfused,
      non-perfused). For perfused cells only a slight dependency of survival and
      relative ATP concentration on heat dose is observed. In consequence, the
      correlation between survival and relative ATP concentration is weak, described by
      log(SFperf) = 0.7*[ATP-12.4, R2 = 0.79, p < 0.04. For non-perfused cells the
      correlation is stronger resulting in a relationship of log(SFno perf) = 0.6*[ATP]
      9.0, R2 = 0.98, p < 0.0002. Altogether, the presented data suggest that the
      relative ATP concentration measured by HPLC after hyperthermia might be
      predictive for cell survival. On the other hand, a dependence between cell
      survival and long-term changes of NTP/Pi has been found. The results confirm the
      importance of tumour perfusion for hyperthermia-induced metabolic changes and
      cytotoxicity and therefore, for the therapeutic outcome.

PMID- 9024929
TI  - Arrhenius analysis of the thermal response of human colonic adenocarcinoma cells
      in vitro using the multi-target, single-hit and the linear-quadratic model.
AB  - In order to compare the intrinsic thermal sensitivity of different malignant cell
      lines the multi-target, single-hit model has been widely accepted. It is even
      applied in clinical hyperthermia by the so-called thermal isoeffect dose (TID)
      concept originated from this model. The second model which is preferentially used
      to describe radiation survival curves is the linear-quadratic (LQ) model which
      can be also applied to thermal response. Interestingly, no breaking point and
      different activation energies are obtained with this model. In the present paper
      we demonstrate this discrepancy with the two human colonic adenocarcinoma cell
      lines WiDr and SW620. Our results further validate the already earlier published
      persuasion, that neither the multi-target, single-hit model, nor the LQ model are
      adequate to describe hyperthermic survival. Since both models give completely
      different results, further data aquisition of isoeffect factors, breaking points
      and activation enthalpies based on the multi-target, single-hit model only, is
      unprofitable until advanced models of thermal inactivation have been developed.

PMID- 9024930
TI  - Long duration-mild whole body hyperthermia of up to 12 hours in rats:
      feasibility, and efficacy on primary tumour and axillary lymph node metastases of
      a mammary adenocarcinoma: implications for adjuvant therapy.
AB  - The feasibility and efficacy of low temperature (40 degrees C) long duration
      whole body hyperthermia (LL-WBH) was investigated in rats bearing a highly
      metastatic mammary adenocarcinoma (MTLn3). We compared the treatment effects of
      various durations of LL-WBH (40 degrees C for 2-12 h) to that of conventional
      short duration-high temperature WBH (SH-WBH, 41.5 degrees C for 2 h). SH-WBH, 2 h
      LL-WBH, and 4 h LL-WBH resulted in only modest primary tumour growth delays
      (TGDs) of 0.9, 1.1 and 1.8 d (days) respectively. In contrast, significantly
      increased TGDs of 2.8, 3.2, 2.6, and 3.1 d were achieved with 6, 8, 10 and 12 h
      LL-WBH, respectively (p < 0.05 compared to SH-WBH, 2 h-LL-WBH, and 4 h-LL-WBH).
      Notably, LL-WBH reduced the incidence of axillary lymph node metastasis at 14
      days post-treatment, from 100% in normothermic controls and 92% after SH-WBH, to
      33, 40, 50, and 60% following 4, 6, 8 and 10 h LL-WBH respectively. When the
      duration of LL-WBH was extended to 12 h, no reduction in axillary lymph node
      metastasis was observed. Normal tissue toxicity of LL-WBH appeared to be minimal
      and LL-WBH durations of up to 12 h were well tolerated. These data show that LL
      WBH for durations of from 4 to 10 h has greater antitumour activity than SH-WBH,
      against mammary adenocarcinoma, suggesting that LL-WBH may have therapeutic
      potential in the treatment of malignant disease.

PMID- 9024931
TI  - Brain hyperthermia alters local cerebral glucose utilization: a comparison of
      hyperthermic agents.
AB  - Microwaves have been proposed to alter neural functioning through both thermal
      and non-thermal mechanisms. We attempted to determine if local cerebral glucose
      utilization (LCGU) depends on the type of hyperthermic agent employed. We exposed
      the heads of rats to two different hyperthermic agents (5.6 GHz microwave
      exposure or exposure to hot/moist air) to create a 2 degree C rise in midbrain
      temperature. Other rats were sham exposed and remained normothermic. The 2-Deoxy
      D-glucose (2DG) autoradiographic method was then used to determine LCGU during a
      45-min period of stable hyperthermia. Hyperthermia (created by either
      hyperthermic agent) caused a general rise in brain glucose utilization. Hot-air
      exposed rats showed significantly higher LCGUs than microwaved rats in portions
      of the motor cortex, hypothalamus, lateral lemniscus and the substantia nigra
      (reticulata). Microwave exposure did not produce significantly higher levels of
      LCGU (compared to hot-air exposed hyperthermic controls) in any of the 47 brain
      areas sampled. A time analysis of lateral hypothalamic (LH) temperature during
      these different heating procedures revealed that microwave exposure produced a
      more-rapid rise in temperature than did not/moist air. Thus, we wondered if the
      nuclei-specific differences in LCGU could be explained by localized differences
      in rate of brain heating during the two hyperthermic treatments. In a second
      study we carefully matched both the rate of lateral hypothalamic temperature rise
      and the peak temperatures achieved by our two hyperthermic methods and again
      measured LH LCGUs. We found that this precise matching eliminated the difference
      in hypothalamic LCGU previously observed following microwave or hot-air exposure.
      These data suggest that hyperthermia causes a general rise in brain metabolism
      and that (as long as steady state and rate of local brain temperature increase
      are well matched) microwave and hot-air induced hyperthermia produce similar
      changes in LCGU.

PMID- 9024932
TI  - Effect of lactic acid in tumours on antitumour activity of hyperthermia.
AB  - The change of lactic acid concentration in the tumour after intraperitoneal
      administration of 5 g/kg glucose, and the effect of the lactic acid concentration
      on antitumour activity of hyperthermia were studied in an experimental murine
      tumour. The lactic acid concentration in SCC VII tumours transplanted into the
      legs of C3H/HeJ male mice was measured by gas chromatography. Local hyperthermic
      treatment to the tumour was performed with a water bath at 43 degrees C for 40
      min. Antitumour effects were evaluated by measuring tumour volume doubling time
      (DT) as an index. The mean concentration of lactic acid in the tumour was 10.4
      mumol/g in the no-treatment group. The lactic acid concentration gradually
      increased after glucose administration, reaching a significantly high
      concentration of 20.0 mumol/g at 90 min later. The DTs in the no-treatment group
      and hyperthermia alone group were 2.4 and 3.7 days respectively. The DTs in the
      glucose administration groups shortly before, 30 and 60 min before the
      hyperthermia were 3.6, 3.6 and 5.6 days respectively. The DT in the 60 min group
      was significantly extended (p < 0.0001). Hyperthermia during the period of
      increased lactic acid concentration significantly prolonged the DT of the tumour.
      These results clearly showed that an increase of lactic acid concentration in the
      tumour improved the effect of local hyperthermia.

PMID- 9024933
TI  - Thermal enhancement of the effect of ifosfamide against a spontaneous murine
      fibrosarcoma, FSa-II.
AB  - The effect of hyperthermia on the cytotoxicity of 3-(2-chloroethyl)-2-[(2
      chloroethyl)amino]-tetrahydro-2H-,1,3, 2-oxazaphosphorine-2-oxide, ifosfamide
      (IFO) was investigated in vivo. Tumours were early generation isotransplants of a
      spontaneous C3Hf/Sed mouse fibrosarcoma, FSa-II. The tumour cell suspensions
      containing approximately 2 x 10(5) cells were transplanted into the dorsal site
      of the C3Hf/Sed mouse foot. Hyperthermia was given by immersing the tumour
      bearing foot into a constant temperature water bath set at 41.5 degrees C for 0
      90 min when tumours reached 34 mm3. IFO was administered i.p. immediately before
      hyperthermia. Tumour response was studied by the tumour growth (TG) time assay;
      namely, the TG time or the time for one-half of the treated tumours to reach 700
      mm3 from the initial treatment day was determined and the dose-response curves
      was fitted between the TG time and IFO dose. The anti-tumour effect of IFO was
      enhanced at this elevated temperature. The thermal enhancement ratio (TER) or the
      ratio of the slope of dose-response curve at 41.5 degrees C to that of dose
      response curve without hyperthermia was relatively small for a short treatment
      time of 30 min. This TER was smaller for IFO than the TERs for cyclophosphamide
      (CY) and BCNU which had been studied in our laboratory. However, the TER for IFO
      increased greatly with a prolongation of treatment time from 30 to 90 min, and
      exceeded the TER for CY. The TERs were 1.5, 2.6 and 3.6 for heating time of 30,
      60, and 90 min, respectively, indicating that a long treatment time such as 90
      min at moderately elevated temperatures could result in a substantial enhancement
      of the antitumour effect of IFO.

PMID- 9024934
TI  - Mild hyperthermia disturbs normal brains cells rather than that it helps killing
      tumours.

PMID- 9024935
TI  - Strain differences in the cytotoxic activity and TNF production of murine
      macrophages stimulated by lentinan.
AB  - The effect of lentinan, a glucan type immunomodulatory polysaccharide was studied
      on the antitumor cytotoxicity and on the TNF secretion of peritoneal macrophages
      in inbred H-2 congeneic mouse strains under in vivo and in vitro conditions. The
      cytotoxic activity and TNF secretion of murine macrophages was found to be
      elevated by lentinan in vitro and in vivo conditions. The effectiveness of
      lentinan to induce cytotoxicity and TNF secretion was highly influenced by the
      genotype of the host. The increased cytotoxicity of macrophages was modified by
      the H-2 and the background genes. The black background and the H-2a and H-2d
      haplotypes were associated with high responsiveness, while the albino and agouti
      background and the H-2b and the H-2k haplotypes with low responsiveness to
      lentinan treatment. The degree of TNF secretion of macrophages stimulated by
      lentinan was influenced by the H-2 genes only. Similarly, to the macrophage
      cytotoxicity the TNF secretion in the H-2a and H-2d haplotypes were found to be
      high, on the other hand, in the H-2b and H-2k were low.

PMID- 9024936
TI  - Fibronectin inhibits the cytotoxic effect of ricin A chain on endothelial cells.
AB  - We have previously reported that after in vitro treatment with deglycosylated
      ricin A chain (dgRTA), human umbilical vein endothelial cells (HUVECs) undergo
      changes in morphology including cell rounding and disruption of monolayers. The
      present studies were carried out to determine whether these changes were related
      to the disruptions in endothelial cell (EC) interactions with the extracellular
      matrix. To this end, we examined the effect of dgRTA on HUVECs in the presence of
      fibronectin (Fn), an extracellular matrix protein, which plays a role in the
      maintenance of vascular integrity. The addition of exogenous Fn greatly inhibited
      dgRTA-mediated morphological changes in HUVEC monolayers, dgRTA-mediated
      inhibition of [3H]thymidine incorporation in HUVECs and the binding of 125I-dgRTA
      to HUVECs. Should the same phenomenon occur with RTA-based immunotoxins (ITs) in
      vivo, this might shed light on the development of dgRTA-mediated vascular leak
      syndrome (VLS) during IT therapy and provide new insights into how to decrease
      this toxicity in patients.

PMID- 9024937
TI  - Kinetics of serum granulocyte-colony stimulating factor (G-CSF) concentration and
      G-CSF receptor expression during G-CSF treatment of cyclophosphamide-treated
      mice.
AB  - We analyzed the kinetics of leukocyte number, serum granulocyte colony
      stimulating factor (G-CSF) concentration, and G-CSF receptor expression in mice
      after recombinant human (rh) G-CSF treatment. Intraperitoneal (i.p.) injection
      with 200 mg/kg of cyclophosphamide (CP) induced a transient decrease of leukocyte
      number in blood and spleen. Daily i.p. inoculation of a low dose of rhG-CSF (1
      microgram/kg/day) from day 1 of CP injection for 8 days resulted in a significant
      increase of spleen cell number from day 5 to day 8, while serum rhG-CSF
      concentration decreased to an undetectable level on day 7. Furthermore, daily
      i.p. inoculation of high dose rhG-CSF (100 micrograms/kg/day) for 5 days to CP
      injected mice induced a significant increase of leukocytes from day 3 to day 6 in
      both peripheral blood and spleen, and the increase was higher than that observed
      after low dose G-CSF treatment. In the course of the high dose rhG-CSF treatment,
      however, serum rhG-CSF concentration decreased from day 3, which is earlier than
      the decrease of serum rhG-CSF seen after low dose rhG-CSF treatment. A reverse
      transcription-polymerase reaction analysis of mRNA expression showed that spleen
      cells from high dose rhG-CSF-treated mice on day 4 and day 6 expressed more than
      10 times higher levels of membrane G-CSF receptors than did those obtained before
      rhG-CSF treatment. All these results suggest that decrease of serum G-CSF during
      daily G-CSF treatment does not always indicate neutralization of G-CSF, but
      implies that the inoculated G-CSF is still stimulating granulocytes and their
      precursors by binding to membrane G-CSF receptors which are up-regulated by G-CSF
      treatment. This observation is important when we measure pharmacokinetics of G
      CSF in patients chronically injected with G-CSF.

PMID- 9024938
TI  - Vesnarinone is a selective inhibitor of macrophage TNF(alpha) release.
AB  - Vesnarinone is an experimental drug that has been used successfully in the
      treatment of congestive heart failure patients. In this report we investigate the
      effect of vesnarinone on the cytokine secretory products of mononuclear
      phagocytes. In a concentration-dependent manner, the drug inhibits the
      endotoxin(LPS)-stimulated release of tumor necrosis factor (TNF) alpha and
      suppresses interleukin(IL)-6 release, but does not affect the release of IL-1
      alpha, IL-10 and leukemia inhibitory factor (LIF) by mouse peritoneal
      macrophages. Using competitive polymerase chain reaction (PCR) analyses, we find
      that vesnarinone significantly reduces TNF(alpha), but not IL-10 mRNA. In
      addition to LPS, the drug inhibits TNF(alpha) release induced by several other
      stimuli. The inhibitory effect of the drug on the TNF(alpha) biosynthesis can be
      observed in differentiated human monocytes, in macrophage cell lines, and in
      synovial adherent cells from rheumatoid arthritis patients. Although the precise
      mode of action of vesnarinone in the signal transduction pathway leading to the
      selective inhibition of TNF(alpha) is not known, the drug might be useful in the
      treatment of diseases involving that cytokine.

PMID- 9024939
TI  - Enhancement of in vivo production of IL-1 alpha and IL-6 in mice by Y-25510, a 1H
      pyrazolo[3,4-b]pyridine-1 acetic acid derivative.
AB  - The serum concentrations of interleukin(IL)-1 alpha and IL-6 in C57BL/6 and
      C3H/HeN mice reached the maximum at 12-16 h after the intravenous treatment with
      (+/-)-3-[4-(2-dimethylamino-1-methylethoxy)- phenyl]-1H-pyrazolo[3,4-b]pyridine-1
      acetic acid (Y-25510) at a dose of 3 mg/kg, and the concentration of IL-10 did at
      20 h after the treatment. By repeated treatments with Y-25510 to C57BL/6 mice for
      14 days, the maximal values of IL-1 alpha and IL-6 at day 14 were respectively
      6.6 times and 5.7 times relative to those on day 1. Neither the counts of
      peripheral leukocytes nor those of platelets were, however, increased until day
      15. The repeated treatment with Y-25510 followed by anti-IL-10 antibody for 14
      days was significantly more effective than that with Y-25510 alone in increasing
      the concentrations of IL-1 alpha and IL-6 in C3H/HeN mice. In addition, both the
      counts of peripheral leukocytes and platelets were significantly increased at day
      18. In conclusion, Y-25510 enhanced not only the production of endogenous IL-1
      alpha and IL-6 but also that of IL-10 in healthy mice. As a result, in normal
      conditions, both the counts of peripheral leukocytes and platelets were never
      increased because of the inhibitory effect of endogenously produced IL-10.

PMID- 9024940
TI  - Relationship between NO-synthase activity and TNF-alpha secretion in mouse
      macrophage lines stimulated by a muramyl peptide entrapped in nanocapsules.
AB  - The present study evaluates the ability of a new drug carrier: nanocapsules of
      poly(D,L-lactide) containing muramyldipeptide-L-alanyl-cholesterol (MTP-Chol NC)
      to induce activation of mouse macrophage cell lines. MTP-Chol NC stimulated
      nitric oxide (NO) expression and tumor necrosis factor-alpha (TNF-alpha)
      production, these are two important mediators of macrophage-mediated
      cytotoxicity. The encapsulated form was more effective than free
      muramyldipeptide, at low immunomodulator concentrations. The dose-response curves
      were completely different for NO and TNF-alpha, implying different regulatory
      mechanisms. In RAW 264.7 cells, the addition of anti-TNF-alpha antibodies during
      the activation period did not affect the level of nitrite induced by MTP-Chol Nc
      and lipopolysaccharide. Therefore, autocrine stimulation by TNF-alpha did not
      contribute to NO production. On the other hand, the presence of an NO synthase
      inhibitor led to an increase in TNF-alpha secretion. In J774.A1 cells, which were
      activated by MTP-Chol NC and interferon-gamma, TNF-alpha production seemed to act
      as a second messenger. Thus, under certain conditions, NO can play a role in
      modulating the cytotoxic activities of mouse macrophages.

PMID- 9024941
TI  - Comparison of antiproliferative effects of 1-histamine-2 receptor antagonists,
      cimetidine, ranitidine, and famotidine, in gastric cancer cells.
AB  - In the immune system, histamine is known to suppress cytotoxic T-lymphocytes and
      nitrogen induced lymphocyte thymidine uptake, down-regulate some cytokines, and
      activate suppressor T-lymphocytes, and in the gastrointestinal system, histamine
      was reported to have trophic effects on gastrointestinal epithelial cells.
      Enhanced rates of cell proliferation by histamine are implicated in the
      pathogenesis. This study was designed since there is a lack of comparative data
      about the cell proliferations of histamine-2 receptor antagonist (H2-RA),
      cimetidine, ranitidine, and famotidine, in gastric cancer. KATO-III and AGS cell
      lines were used in this experiment. The concentrations of the histamine and
      cimetidine were 10(-5)-10(-8) M, respectively and those of ranitidine and
      famotidine were 10(-6)-10(-9)M, respectively. Cell proliferation after drug
      treatment was evaluated by direct cell counting, [3H]thymidine incorporation, and
      MTT assay. Activities of ornithine decarboxylase (ODC), a rate limiting enzyme in
      polyamine synthesis, were measured after each drug treatment. Protein kinase A, a
      cAMP-dependent protein kinase system, was assayed using [alpha-32P]ATP. Histamine
      showed statistically significant cell proliferating effects in a dose-dependent
      manner (P < 0.001), the maximal effect in 10(-5) M concentration. ODC activities
      were increased in accordance with the increment of cell numbers after histamine
      treatment. Cimetidine reversed the histamine-stimulated cell proliferation
      significantly, the maximal effect in 10(-5) M concentration (P < 0.01). Although
      ranitidine showed the tendency to attenuate the cell proliferation dose
      dependently, but without statistical significance, famotidine did not show such
      an effect at all. cAMP-dependent protein kinase activities were significantly
      increased following 10(-5) M histamine treatment, also reversed significantly by
      cimetidine co-administration (P < 0.01). Beneficial clinical outcomes could be
      anticipated from cimetidine treatment in patients with gastric cancer by anti
      proliferating effects against gastric cancer cells. These effects of H2-RA are
      likely to be mediated by specific interactions at the H2-receptor.

PMID- 9024942
TI  - Comparison of the in vivo effects of morphine and methadone on natural killer
      cell activity in spleen, peritoneal cavity, and lungs in rats.
AB  - Opiates and opioid agents are known to affect the immune system. In humans this
      includes alterations in natural killer (NK) cell activity. Morphine is reported
      to reduce in vivo spleen NK activity in rats, whereas for methadone only in vitro
      data have been described. In the present paper we describe a systematic study on
      the chronic effects of well-known opiates, comparing for the first time the
      effects of morphine and methadone on NK cell activity in various organs: in
      addition to spleen, also in the peritoneal cavity, and lungs. In all organs the
      NK activity was determined using three effector: target cell ratios. Morphine and
      methadone given by food during 6 weeks decreased the NK cell activity in rat
      spleen, supporting published data on morphine. The role of the opiate receptor is
      discussed. However, the overall action of morphine could not be described as
      suppressive because stimulation of NK cell activity in the peritoneal cavity and
      lungs by morphine was found. In contrast, methadone induced a decrease in the NK
      cell activity in these organs. Apart from these differential expressions of
      morphine- and methadone associated effects on NK cell activity, the findings
      demonstrate the potential adverse effects of these opiates on an important
      antiviral defence mechanism.

PMID- 9024943
TI  - Hamster cardiac xenograft in rat ear: effect of cyclosporine A and leflunomide on
      survival.
AB  - The survival was determined of hamster-heart grafts subcutaneously placed in rat
      ears. Thirteen out of the 14 grafts tested in rats without immunosuppression were
      rejected by day 7 post-transplantation, and the one graft was rejected by day 9.
      Cyclosporine A fully protected the grafts for 2 weeks, the entire experimental
      period. By contrast, leflunomide seemed only to delay the graft rejection. The
      formation of antidonor antibodies was fully suppressed by both drugs. These
      results reveal a pivotal role of T-cells in this model. The results with
      leflunomide suggest that this drug preferentially affected humoral responses in
      our study.

PMID- 9024944
TI  - Early and late phase bronchoconstrictions in conscious sensitized guinea-pigs
      after macro- and microshock inhalation of allergen and associated airway
      accumulation of leukocytes.
AB  - Guinea-pigs were sensitized by i.p. injection of 10 micrograms OA and 100 mg
      aluminium hydroxide in 1 ml normal saline. Fourteen to twenty-one days after
      sensitization, animals were exposed to macroshock (1% OA for 2 min) or microshock
      (0.01% for 60 min) inhalation challenges with OA. Animals were protected against
      fatal anaphylaxis in the case of macroshocks with mepyramine (30mg/kg i.p.) 30
      min before exposure. Specific airway conductance (sGaw) was measured in conscious
      animals by whole body plethysmography at intervals up to 72 h after challenge. An
      early phase bronchoconstriction peaked significantly (P < 0.05) at 15 min after
      both macroshock and microshock OA exposures, with maximum falls in sGaw of 70.8
      +/- 3.8 and -40.0 +/- 5.9%, respectively. These had resolved after 5 h. A late
      phase bronchoconstriction peaked variably between 17 and 24 h: the mean peak
      falls in sGaw after the macro- and microshock challenges were significantly
      different from baseline (P < 0.05), at -21.6 +/- 3.7 and -38.0 +/- 3.9%,
      respectively. Control exposures of OA-sensitized guinea-pigs to saline for either
      2 or 60 min, in place of OA, produced no significant variation in sGaw values
      over the predicted early and late phases. Bronchoalveolar lavage (BAL) performed
      at 5 or 24 h after OA challenge revealed significant increases in total cell
      numbers (P < 0.05) at 5 and 24 h after the OA macroshock challenge and at 24 h
      after the microshock, compared with saline challenges. Differential cell counts
      showed a significant (P < 0.05) increase in the proportion of neutrophils at 5 h
      and of neutrophils and eosinophils at 24 h after the macroshock exposure to OA,
      compared with saline controls. A significant (P < 0.05) increase in the
      proportion of eosinophils also occurred in BAL fluid at 24 h after microshock OA
      challenge. Neutrophils, however, did not alter at 24 h, yet a late phase
      bronchoconstriction was recorded. Thus, macroshock (with mepyramine cover) and
      microshock (without mepyramine cover) OA challenges result in both early and late
      phase bronchoconstrictions. The late phase is associated with influx of
      eosinophils in both models but neutrophils only appear after the macroshock,
      indicating that late phase responses may not involve neutrophil infiltration to
      the airways.

PMID- 9024945
TI  - Immunomodulatory activity of amphiphilic antimicrobials on mouse macrophages.
AB  - A quaternary ammonium salt (1-methyldodecyl)-trimethylammonium iodide, a
      structurally analogous amine oxide (1-methyldodecyl)-dimethylamine-N-oxide and
      the amine oxide lacking long alkyl chain trimethylamine-N-oxide were tested for
      their immunomodulatory activity. Inbred mice strain C57/BL6 were pretreated for 7
      days by the compounds under study. The activity of elicited peritoneal
      macrophages was also tested. Both compounds have a long alkyl chain. In
      concentrations of 10(-6) M there was a significant increase of the phagocytic,
      candidacidal and lysozyme activities of the cells. We also observed a suppressed
      peroxidase activity. The colicidal activity of both the peritoneal and spleen
      cells were not affected. The amine oxide lacking the long alkyl chain has the
      same effect at high concentration. A similarity between the effects of the
      amphiphilic compounds on the macrophages and their antimicrobial efficacy elicits
      the conclusion that both activities are caused by their ability to interact with
      the cell membranes.

PMID- 9024946
TI  - In vitro lymphotoxicity and selective T cell immunotoxicity of high doses of
      acyclovir and its derivatives in mice.
AB  - The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7
      isomer (7-ACV) and its two derivatives: N2-acetyl ACV (ac-ACV) and N2,O-diacetyl
      ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in
      vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated
      derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell
      proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo)
      did not exhibit any inhibitory potential of ACV. However, reduction in the
      absolute number of CD3+, CD8+, and CD25+ cells, but not Ig+ cells, was noted at
      high concentrations of ACV and its derivatives, suggesting a selective T cell
      cytotoxicity. Similarly, the in vivo exposure revealed selective T cell
      immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2+
      and CD8+ cells was not accompanied with any marked changes in the Ig+ population.
      The CD4+/CD8+ ratio was affected both in vitro and in vivo by high concentrations
      of ACV.

PMID- 9024947
TI  - The trap of protopathic bias in neuropsychiatric research.

PMID- 9024948
TI  - Hypersensitivity to carbon dioxide as a disease-specific trait marker.
AB  - There is now substantial evidence that an abnormal threshold for suffocation
      alarm underlies panic disorder. Because this disorder is highly familial,
      evidence of an abnormal suffocation threshold may be apparent in high-risk
      individuals before they develop clinical illness. To explore this possibility, we
      used a single inhalation of 35% CO2 vs. air to evaluate 11 subjects who had at
      least one first-degree relative with DSM-III-R panic disorder, 13 who had at
      least two relatives treated for mania or for depression (HR-AD), and 15 low-risk
      controls who had no family history of panic disorder, affective disorder, or
      alcoholism (LR-C). All were aged 18-34 and had no history of panics or of any
      Research Diagnostic Criteria disorder. Five (45.5%) of the subjects at high risk
      for panic disorder, but none of the LR-C subjects (p = .007), nor any of the HR
      AD subjects (p = .011), developed a panic attack following inhalation of the CO2
      mixture.

PMID- 9024949
TI  - Comparative antidepressant effects of intravenous and intrathecal thyrotropin
      releasing hormone: confounding effects of tolerance and implications for
      therapeutics.
AB  - A significant amount of preclinical and human data indicate that thyrotropin
      releasing hormone (TRH) has antidepressant effects. Although early studies
      showing these effects using intravenous TRH were not consistently replicated, it
      has been suggested that this could be explained by its poor blood-brain barrier
      penetration. For this reason we compared the antidepressant effect of intrathecal
      and intravenous TRH administered in a double-blind design to 2 treatment
      refractory patients with bipolar II disorder. Each experienced a robust
      antidepressant response by both routes; subsequent open trials of intravenous TRH
      also were effective until apparent tolerance developed. Intrathecal TRH was
      readministered and both subjects again experienced robust antidepressant
      responses. These preliminary data suggest a differential mechanism of tolerance
      to the two routes of administration and raise the possibility that a subgroup of
      patients may be responsive to the antidepressant effects of TRH independent of
      its route of administration.

PMID- 9024950
TI  - Heritability of aggression and irritability: a twin study of the Buss-Durkee
      aggression scales in adult male subjects.
AB  - To determine the degree of genetic and environmental influences on assessments of
      aggression and irritability in male subjects, the "Motor Aggression" subscales of
      the Buss-Durkee Hostility Inventory (BDHI) were mailed to 1208 male twins in the
      Vietnam Era Twin Registry. Data from monozygotic 182 and 118 dizygotic twin pairs
      were available and were analyzed using model-fitting procedures. Three of the
      four BDHI subscales demonstrated significant heritability of a nonadditive
      nature: 40% for Indirect Assault, 37% for Irritability, and 28% for Verbal
      Assault. Additive genetic variance accounted for 47% of the individual
      differences for Direct Assault. Nonshared, but not shared, environmental
      influences contributed to explaining the variance in the model, with estimates
      ranging from 53% (Direct Assault) to 72% (Verbal Assault). Because some of these
      BDHI scales have been shown to correlate with indices of central serotonin
      function, it is possible that impulsive aggression, as reflected by these scales,
      is heritable in men.

PMID- 9024951
TI  - A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on
      brain.
AB  - Women with Turner's syndrome (TS) allow us to study the neurobiological
      associates of cognitive and behavioral abnormalities because they lack one/part
      of one X chromosome, and endogenous estrogen. We studied 13 healthy controls
      (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6
      years). We measured cognitive abilities using neuropsychological tests, and
      cerebral metabolic rates for glucose with positron emission tomography. Compared
      to controls, TS subjects had significant absolute hypermetabolism in most brain
      areas; however, normalized metabolism was significantly lower in TS subjects than
      controls in the insula and association neocortices bilaterally, and there were
      significant differences in functional metabolic associations of brain region
      pairs originating in occipital cortex bilaterally, and within the right
      hemisphere. There were significant correlations between right-left cognitive and
      metabolic asymmetries in the TS group. Also, within TS a preliminary analysis
      demonstrated "X chromosome dosage" effects in language ability and left temporal
      metabolism, asymmetry of right-left test scores, and parietal metabolism. We
      hypothesize that within TS: i) generalized brain hypermetabolism reflects global
      abnormalities in neuron packing; ii) neuronal abnormalities occur in association
      neocortex that differ in nature or extent from whole brain and are associated
      with significant differences in normalized metabolism; iii) cognitive deficits
      are related to brain metabolic abnormalities; and iv) social-behavioral problems
      may be related to abnormalities of brain metabolism. Moreover, in human brain the
      X chromosome involved in development of the association neocortices.

PMID- 9024952
TI  - Allelic association of a dopamine transporter gene polymorphism in alcohol
      dependence with withdrawal seizures or delirium.
AB  - Hereditary factors confer susceptibility to alcohol dependence. Alcohol mediates
      its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine
      system. The role of the dopamine transporter in terminating dopaminergic activity
      in synaptic neurotransmission suggests that variants of the dopamine transporter
      gene (DAT1) might contribute to individual differences in vulnerability to
      addictive behavior. Our population-based association study investigated whether
      variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics
      and clinically more homogeneous subgroups formed by: positive family history,
      early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1
      and 2 alcoholics. Analyzing a VNTR polymorphism in the 3' untranslated region of
      DAT1, we found a significantly increased prevalence of the nine-repeat allele in
      93 alcoholics displaying withdrawal seizures or delirium, compared with 93
      ethnically matched nonalcoholic controls (p = 0.003; OR = 2.44; 95% confidence
      interval: 1.35-4.43). Our data provide evidence that a major genetic determinant
      of DAT1 influences vulnerability to severe alcohol withdrawal symptoms.

PMID- 9024953
TI  - Dopamine D2 receptors quantified in vivo in human narcolepsy.
AB  - Assays in brain tissues from humans suffering from narcolepsy, and from
      genetically narcoleptic dogs have suggested that dopamine function may be
      disturbed in this condition. We have used the specific D2 receptor ligand N-(3
      [18F]fluoropropyl)-spiperone and positron tomography to study a group of 6 well
      characterized medication-free, HLA-DR2 DRW15 DW6-positive narcoleptic patients
      and a group of age- and sex-matched control individuals during life. We found no
      difference in striatal D2 receptor binding between these two groups. These
      results suggest that narcolepsy is not associated with alterations in D2 receptor
      density and affinity.

PMID- 9024954
TI  - Dehydroepiandrosterone (DHEA) treatment of depression.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal
      steroid hormones that decrease with aging and may have significant
      neuropsychiatric effects. In this study, six middle-aged and elderly patients
      with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly
      administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve
      circulating plasma levels observed in younger healthy individuals. Depression
      ratings, as well as aspects of memory performance significantly improved. One
      treatment-resistant patient received extended treatment with DHEA for 6 months:
      her depression ratings improved 48-72% and her semantic memory performance
      improved 63%. These measures returned to baseline after treatment ended. In both
      studies, improvements in depression ratings and memory performance were directly
      related to increases in plasma levels of DHEA and DHEA-S and to increases in
      their ratios with plasma cortisol levels. These preliminary data suggest DHEA may
      have antidepressant and promemory effects and should encourage double-blind
      trials in depressed patients.

PMID- 9024955
TI  - Physiologic responses to loud tones in Israeli veterans of the 1973 Yom Kippur
      War.
AB  - Eyeblink and autonomic components of the acoustic startle response were evaluated
      in a community sample of Israeli veterans of the Yom Kippur war. Individuals were
      solicited by mail and telephone to participate in the study; they were not
      seeking treatment or compensation. Nineteen Israeli veterans with current
      posttraumatic stress disorder (PTSD) and 74 veterans without PTSD were exposed to
      15 consecutive 95-dB, 500-msec, 1000-Hz tones with 0-msec rise and fall times,
      while orbicularis oculi electromyogram, skin conductance, and heart rate
      responses were measured. Individuals with PTSD produced larger averaged heart
      rate responses, and a slower decline in skin conductance responses, across the 15
      tone presentations compared to non-PTSD subjects. There was no group difference
      in the magnitude of the averaged electromyogram response. Results of this study
      replicate previous findings of increased autonomic responses to loud tone stimuli
      in this disorder.

PMID- 9024956
TI  - Auditory P300 topography and neuropsychological test performance: evidence for
      left hemispheric dysfunction in schizophrenia.
AB  - Asymmetrical topography of the auditory P300 with reduced left hemispheric
      amplitudes and, consequently, a right-lateralized peak of the P300 electrical
      field has been repeatedly reported in schizophrenia. This was interpreted as an
      indication of reduced left-hemispheric activity during the simple cognitive P300
      task. Since generator locations calculated from the surface potentials are
      ambiguous, further evidence is required to support this conclusion. In the
      present study, 13 stabilized DSM-III-R schizophrenic patients were studied with
      an auditory P300 paradigm and neuropsychological methods sensitive to functional
      brain asymmetries. The tests included the verbal paired associates test
      (Goldstein et al 1988, Cortex 24:41-52) and the nonspatial conditional
      associative learning test (Petrides 1985, Neuropsychologia 23:601-614). A
      significant correlation was found between right-sided lateralization of the P300
      maximal positivity and neuropsychological evidence for left hemispheric temporal-
      hippocampal dysfunction. Attentional performance was correlated with P300
      amplitudes. The results of this study provide further evidence that right-sided
      lateralization of the P300 peaks results from dysfunction of left-hemispheric
      neuronal generators.

PMID- 9024958
TI  - Pulsatile adrenocorticotropic hormone: an overview.
AB  - Adrenocorticotropic hormone (ACTH) is secreted by corticotrophic cells in
      pulsatile bursts. This paper reviews the extant literature on the phenomenon of
      pulsatile ACTH after addressing basic issues of hormone pulsatility in
      neuroendocrine systems. The following themes emerged from reviewing 51 studies
      measuring plasma ACTH at intervals of 20 min or less: marked inter-individual
      variability in the pattern of ACTH, the dependence of pulse identification on
      sampling frequency, the similarity in ACTH pulse amplitude and frequency across
      species, and the predominance of amplitude over frequency changes in ACTH pulses
      in altered physiological states. As the hypothalamic-pituitary-adrenocortical
      (HPA) axis plays a critical role in orchestrating adaptation and survival, the
      ability to modulate the shape of ACTH signals may prove to be an important means
      of transmitting complex information to ACTH responsive cells. The clinical and
      neurobiological significance of temporal alterations in ACTH secretion represents
      an area for future investigation.

PMID- 9024957
TI  - Suppression of nocturnal plasma melatonin levels by evening administration of
      sodium valproate in healthy humans.
AB  - To investigate the role of gamma-aminobutyric acid (GABA) in the modulation of
      human melatonin production, we studied the effects of the acute administration of
      the GABAergic drug, sodium valproate (VAL), on nocturnal blood melatonin levels
      in healthy subjects. To this purpose, 4 healthy men and 3 healthy women, aged 24
      33 years, underwent three experimental sessions in which they received orally 400
      mg VAL, 800 mg VAL, or placebo, in random order, according to a double-blind
      design. The drug administration was done at 19:00 hours; thereafter, blood
      samples were collected over the night, in dark conditions with the help of a red
      light. As compared to placebo, VAL, at the dosage of both 400 and 800 mg,
      significantly suppressed nocturnal blood melatonin levels, the higher dose being
      slightly more effective than the lower one. The maximum suppression coincided
      with the highest plasma levels of valproic acid. These findings support the view
      that endogenous GABA may participate in the modulation of the activity of the
      human pineal gland.

PMID- 9024959
TI  - Low plasma cortisol in bulimia nervosa patients with reversed neurovegetative
      symptoms of depression.

PMID- 9024960
TI  - Electroencephalographic sleep and urinary free cortisol in adolescent depression:
      a preliminary report of changes from episode to recovery.

PMID- 9024961
TI  - Diurnal urine volume estimates in schizophrenic patients with polydipsia during
      water-loaded versus nonloaded states.

PMID- 9024962
TI  - Venlafaxine and metabolites are very weak inhibitors of human cytochrome P450-3A
      isoforms.

PMID- 9024972
TI  - Ribosomal RNA location in the Antarctic fish Champsocephalus gunnari
      (Notothenioidei, Channichthyidae) using banding and fluorescence in situ
      hybridization.
AB  - A biotinylated 28S rDNA probe was prepared from the genomic DNA of the Antarctic
      ice-fish Champsocephalus gunnari and hybridized to metaphase chromosomes of the
      same species by fluorescence in situ hybridization (FISH). The hybridization
      signal appeared over the whole heterochromatic arm of the submetacentric
      chromosomes bearing the nucleolar organizer regions. The results of rDNA/FISH are
      compared with those coming from classical cytogenetic (C, Q, Ag-NOR, chromomycin
      A3) banding techniques. The in situ detection of a specific DNA sequence offers a
      new more precise perspective for understanding the evolving process in
      chromosomes of Antarctic fish and will provide an interesting contribution to
      comparative cytogenetics of lower vertebrates.

PMID- 9024973
TI  - Combined immunocytogenetic and molecular cytogenetic analysis of meiosis I human
      spermatocytes.
AB  - We have used a combination of immunocytogenetic and molecular cytogenetic
      technology on human spermatocytes to investigate (1) meiosis I chromosome
      pairing, and (2) organization of synaptonemal complex (SC)-associated chromatin
      with respect to whole chromosome paints, unique DNA sequences and repetitive DNA
      of heterochromatic blocks, centromeres and telomeres. It is evident that synapsis
      normally starts at the termini of homologues. In general, synapsis proceeds
      synchronously from termini towards the centre of bivalents without any indication
      of interstitial initiation. Some aberrant meiosis I spermatocytes showed
      asynchronous pairing, demonstrating not only large differences in the degree of
      SC formation between bivalents, but also chromosome alignment without synapsis as
      well as clear interstitial synaptic initiation. It may be the case that alignment
      normally takes place along the entire length of homologues before synapsis occurs
      and that the potential for synaptic initiation exists along the length of
      chromosomes. Telomeric sequences were seen tightly associated with the SCs, as
      might be expected considering their kinetic properties in relation to the nuclear
      membrane. Other repetitive DNA, i.e. centromeric alpha-satellites and classical
      satellites of the heterochromatic blocks 1qh and 9qh, were all found to form
      loops that are associated with SCs only at their bases. A unique DNA cosmid probe
      (21q22.3) was found to produce a hybridization pattern consisting of spots
      located outside SC. The fluorescence in situ hybridization (FISH) signals of
      these spread DNA sequences have a granular appearance, probably reflecting the
      pattern of coiling and chromatin condensation of the target DNAs.

PMID- 9024975
TI  - Characterization of the translocated chromosome using fluorescence in situ
      hybridization and random amplified polymorphic DNA on two Triticum aestivum
      Thinopyrum intermedium translocation lines resistant to wheat streak mosaic or
      barley yellow dwarf virus.
AB  - Fluorescence in situ hybridization (FISH) was used to determine the breakpoint of
      the translocation chromosome in two bread wheat (Triticum aestivum) germplasm
      lines with Thinopyrum intermedium chromatin carrying resistance to either wheat
      streak mosaic virus (WSMV) or barley yellow dwarf virus (BYDV). In addition,
      genome-specific random amplified polymorphic DNA (RAPD) markers were used to
      ascertain the genomic sources of the Th. intermedium chromosome carrying the WSMV
      or BYDV resistance. CI17766, a WSMV-resistant wheat germplasm line derived from
      induced homoeologous pairing by using the ph1b mutant, had a translocation
      chromosome composed of the complete 4AL and about 45% of proximal 4AS from wheat,
      and the entire 4ES of Th. intermedium. The BYDV-resistant translocation line,
      TC14, derived from tissue culture, had a very short distal segment of 7StL from
      Th. intermedium terminally attached to 56% of the proximal 7DL. These
      observations indicate that translocations in these wheat germplasm lines did not
      involve centromeric breaks and fusion but were a result of homoeologous
      chromosomes recombination.

PMID- 9024974
TI  - Scanning ion analytical microscopy for high-resolution detection of 5-bromo-2'
      deoxyuridine incorporation in metaphase chromosomes.
AB  - We investigated the possibilities of using scanning ion analytical microscopy
      (SIAM) to detect bromine in human metaphase chromosomes. The experiments were
      performed after incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine
      (BrdU), into the DNA or by in situ hybridization of a BrdU-labelled probe for the
      subcentromeric repeated DNA sequences. The possibilities offered by this
      microanalytical method were compared with immunofluorescent staining techniques.
      Well-defined maps of bands containing bromide were obtained with metaphase
      chromosomes that had incorporated BrdU during the late S-phase. Their patterns
      were similar to the labelling obtained by immunofluorescence. In addition, SIAM
      reveals the presence of bromine within constitutive heterochromatic regions in
      which BrdU is poorly detected by immunofluorescence. The comparison of the
      12C14N, 31P and 81Br maps of controls and fluorescence plus Giemsa (FPG)
      metaphase chromosomes shows the loss of bromide from DNA during this treatment.
      SIAM emerges as a new powerful microanalytical technology for investigating
      chromosome structure further.

PMID- 9024976
TI  - Transcription of lampbrush chromosomes of a centromerically localized highly
      repeated DNA in pigeon (Columba) relates to sequence arrangement.
AB  - A highly repetitive, centromerically localized DNA sequence (PR1) has been
      isolated from the genomic DNA of two species of pigeon (Columba livia and C.
      palumbus). PR1 is approximately 900 bp long. It includes a sequence that is
      similar to the CENP-B box of mammals. It represents about 5% of the genome in C.
      livia and 2% in C. palumbus. In both species, tandem arrays of PR1 form part of
      larger repeating units. The organization of PR1 repeats and the larger repeating
      units is strikingly different in the two species. The large repeating units in C.
      livia include long (at least 14 units) tandem arrays of PR1 interspersed with
      relatively short intervening sequences. The large repeats of C. palumbus have
      much shorter (4 units or fewer) PR1 arrays interspersed with longer sections of
      non-PR1 DNA. PR1 is transcribed on short lampbrush loops in the centromeric
      regions of all lampbrush bivalents of C. palumbus. In C. livia, it is not
      transcribed at any of the major pericentromeric sites at which it is known to be
      present, although it is transcribed at one minor centromeric site on chromosome
      2. It is proposed that transcription of the noncoding PR1 sequence on lampbrush
      chromosomes of pigeons relates to its genomic organization. The proposal is
      discussed with regard to the 'read-through' hypothesis for transcription on
      lampbrush loops.

PMID- 9024977
TI  - Paternally inherited chromosomal structural aberrations detected in mouse first
      cleavage zygote metaphases by multicolour fluorescence in situ hybridization
      painting.
AB  - We describe a fluorescence in situ hybridization (FISH) procedure for assessing
      zygotic risk of paternal exposure to endogenous or exogenous agents. The
      procedure employs multicolour FISH with chromosome-specific DNA painting probes
      plus DAPI staining for detecting both balanced and unbalanced chromosomal
      aberrations in mouse first-cleavage (1-Cl) zygote metaphases. Four composite
      probes specific for chromosomes 1, 2, 3 or X, each labelled with biotin, plus a
      composite probe specific for chromosome Y labelled with digoxigenin, were used.
      We applied this method to evaluate the effects of paternal exposure to
      acrylamide, a model germ cell clastogen. First-cleavage zygote metaphases,
      collected from untreated females mated to males whose sperm or late spermatids
      were treated with acrylamide, were scored for the induction of structural
      aberrations using both chromosome painting (PAINT analysis) and DAPI analysis.
      Structural chromosomal aberrations were observed in the sperm-derived, but not in
      the egg-derived, pronuclei. While 59.4% of the zygotes had structural aberrations
      by DAPI analysis, 94.1% of the same zygotes had structural aberrations by PAINT
      analysis (P < 0.001), illustrating the increased sensitivity for detecting
      translocations and insertions obtained by adding chromosome painting. These
      findings show that FISH painting of mouse 1-Cl zygotes when used in conjunction
      with DAPI analysis is a powerful model for investigating the cytogenetic defects
      transmitted from father to offspring.

PMID- 9024978
TI  - Chromosomes of Damaliscus (Artiodactyla, Bovidae): simple and complex centric
      fusion rearrangements.
AB  - G- and C-banded karyotypes of Damaliscus hunteri, D. lunatus and D. pygargus were
      compared using the standard karyotype of Bos taurus. Chromosomal complements were
      2n = 36 in D. lunatus jimela, 2n = 38 in D. pygargus phillipsi and D. p.
      pygargus, and 2n = 44 in D. hunteri. The fundamental number in all karyotypes was
      60. Among the three species of Damaliscus, seven autosomal pairs and the X
      chromosomes were conserved. Y-chromosome differences were attributed to
      heterochromatic additions or deletions. Banded karyotypes of the two subspecies
      of D. pygargus exhibited complete homology. Chromosomal complements of D.
      pygargus and D. lunatus differed by a simple centric fusion. However, karyotypes
      of D. pygargus and D. lunatus differed from D. hunteri by numerous centric
      fusions, several of which were related by monobrachial chain complexes. Between
      the karyotypes of D. hunteri and D. pygargus or D. lunatus, there were two chain
      complexes, one involving five chromosomes (chain V) and the other involving 12 in
      pygargus (chain XII) or 13 in lunatus (chain XIII). There were also two simple
      centric fusions between D. hunteri and D. lunatus/D. pygargus; acrocentric
      chromosomes 13, 15, 20 and 22 in D hunteri were fused as 13;15 and 20;22 in D.
      lunatus and D. pygargus.

PMID- 9024979
TI  - Immunocytochemistry of soluble and non-soluble nuclear proteins on squash
      preparations of mammalian meiotic cells.

PMID- 9024980
TI  - Are T cells from healthy heart really only passengers? Characterization of
      cardiac tissue T cells.
AB  - Numerous studies have dealt with occurrence of dendritic cells in various
      nonlymphoid organs such as kidney, liver or heart, whereas lymphocyte patterns in
      these organs have not been analyzed in detail. In the present study, leukocytes
      were quantified as cells/mm2 in the perivascular, interstitial and parenchymal
      tissue sections of normal heart. We measured an overall mean leukocyte count in
      normal heart tissue of 17.0 +/- 2.7 CD45+ leukocytes/mm2, 9.1 +/- 1.8 thereof
      being CD4+ T-helper cells (Th). By comparison, CD8+ T-cytotoxic/suppressor cells
      (Ts) and CD14+ macrophages each accounted for only approximately 2.5 cells/mm2,
      and CD20+ B cells for only 1.3 cells/mm2. These T cells were further
      characterized as either CD45RA+ naive T cells or as CD45RO+ memory T cells.
      Segmentation of the tissue as defined in Section 2 yielded an ascending number of
      CD45RO+ memory T cells from perivascular (0.4 +/- 0.2 cells/mm2) through
      parenchymal (12.8 +/- 3.0 cells/mm2) to interstitial (21.0 +/- 5.3/mm2). By
      contrast, the number of CD45RA+ and Leu-8+ cells decreased from perivascular to
      parenchymal. Peripheral T cells showed a reverse pattern of CD45RA/CD45RO antigen
      expression. Only approximately 3% of T cells expressed activation markers IL-2R
      and IL7R. Our data demonstrate that the majority of T cells in normal heart
      tissue are resting memory tissue T cells and are not contaminating T cells from
      the peripheral blood. The increase in CD45RO+ cells from perivascular to
      parenchymal with a corresponding decrease in CD45RO+ and Leu-8+ heart-tissue T
      cells argues in favor of T-cell traffic in normal heart tissue.

PMID- 9024981
TI  - Effects of phorbol ester on phospholipase D and mitogen-activated protein kinase
      activities in T-lymphocyte cell lines.
AB  - The effects of phorbol 12-myristate 13-acetate (PMA) on the activities of
      phospholipase D (PLD3), mitogen-activated protein kinase (ERK), and c-Jun N
      terminal kinase (JNK) were studied in Jurkat, a human T cell line, and EL4, a
      murine T-cell line. PMA treatment rapidly activated PLD in Jurkat, as detected
      either in intact or broken cells. In contrast, PMA did not stimulate PLD activity
      in EL4 cells. PLD activity was not detected in membranes prepared from EL4 cells.
      Jurkat, but not EL4, expresses a 120-kDa protein recognized by an anti-PLD
      antibody. In both Jurkat and EL4 cells, PMA caused activation of ERKs. Incubation
      of EL4 cells with bacterial PLD increased phosphatidic acid levels, but did not
      activate ERK. In both EL4 and Jurkat cells, co-stimulation with PMA and ionomycin
      stimulated JNK activity. These results show that activation of PLD is not
      required for activation of ERKs or JNKs by PMA in T-cell lines. Thus, while PLD
      activity is expressed in some T-cell lines, the role of this enzyme and its
      products in T-cell activation remain to be elucidated.

PMID- 9024982
TI  - The effects of early and late administration of M-20 derived interleukin-1
      inhibitor on experimental systemic lupus erythematosus.
AB  - M-20 interleukin-1 inhibitor is produced by a myelomonocytic cell line. The
      effects of this molecule, mediated via IL-1 inhibition, include decreased
      proliferative responses of mouse thymocytes, human T-cells and fibroblasts and
      reduction in parameters of acute inflammation. Previously, we have demonstrated
      the emergence of a disease resembling systemic lupus erythematosus (SLE) in naive
      mice immunized with anti-DNA antibodies carrying different pathogenic idiotypes.
      The disease was manifested by increased titers of various mouse antibodies,
      concomitant with the appearance of elevated erythrocyte sedimentation rate (ESR),
      proteinuria and leukopenia. We have applied this model of experimental SLE
      (immunized with MIV-7, a human monoclonal antibody) to evaluate the influence of
      M-20 IL-1 inhibitor, administered at different stages (2 weeks before, 1 month
      and 3 months following immunization) for a period of 2 weeks, on the findings of
      the disease in mice. It was shown that M-20 IL-1 inhibitor given 2 weeks prior to
      the immunization resulted in suppression of the disease induction as documented
      by lower antibody titer level (30%-50% in the immunized mice as compared with
      controls). Furthermore, reduced autoantibody levels were accompanied by other
      beneficial findings consisting of lower ESR, less severe proteinuria and elevated
      leukocyte counts. No beneficial effects of M-20 IL-1 inhibitor were observed when
      the agent was administered 1 or 3 months following immunization. We conclude that
      M-20 IL-1 inhibitor has a favorable effect on experimental SLE in mice, provided
      it is administered before induction of the disease.

PMID- 9024983
TI  - Protective efficacy against malaria of a combination sporozoite and erythrocytic
      stage vaccine.
AB  - Most malariologists believe that optimal malaria vaccines will induce protective
      immune responses against different stages of the parasite's life cycle. A
      multiple antigen peptide (MAP) vaccine based on the Plasmodium yoelii
      circumsporozoite protein (PyCSP) protects mice against sporozoite challenge by
      inducing antibodies that prevent sporozoites from invading hepatocytes. A
      purified recombinant protein vaccine based on the P. yoelii merozoite surface
      protein-1 (PyMSP-1) protects mice against challenge with infected erythrocytes,
      presumably by inducing antibodies against the erythrocytic stage of the parasite.
      We now report studies designed to determine if the PyMSP-1 vaccine protects
      against challenge with sporozoites, the stage encountered in the field, and if
      immunization with a combination of the PyCSP and PyMSP-1 vaccines provides
      additive or synergistic protection against sporozoite challenge. In two
      experiments, using TiterMax or Ribi R-700 as adjuvant, 3 of 19 mice immunized
      with the PyMSP-1 vaccine were completely protected against sporozoite challenge.
      The remaining mice had significantly delayed onset and lower levels of peak
      parasitemia than did control mice (11.1 +/- 2.8% vs. 36.7 +/- 1.6% in experiment
      #2, P < 0.01). Immunization with the combination vaccine reduced by approximately
      50% the level of antibodies induced to PyCSP and PyMSP-1, as compared to that
      induced by the individual components. However, in two experiments, there was
      evidence of additive protection. Six of 19 (31.6%) immunized with the PyCSP
      vaccine, 3 of 19 (15.8%) immunized with the PyMSP-1 vaccine, and 10 of 19 (52.6%)
      immunized with the combination were completely protected against sporozoit
      challenge. This modest increase in protection in the combination group may be a
      reflection of additive anti-PyCSP and anti-PyMSP-1 immunity, since mice in the
      combination group had diminished levels of antibodies to each components. These
      studies indicate that considerable work may be required to optimize the
      construction, delivery, and assessment of multi-stage malaria vaccines.

PMID- 9024984
TI  - Histones interact with immunoglobulins and give them polyspecificity.
AB  - The presence of antihistone antibodies was determined in different commercial
      immunoglobulin preparations. The ability of histones to perform the function of
      cofactor in interaction of immunoglobulin preparations and sera of healthy people
      with charged molecules such as DNA, cardiolipin and phosphatidylcholine, was
      determined. The addition of histones of immunoglobulin preparations or serum
      samples is accompanied by forming the stable complex, components of which
      interact with the charged molecules. The capacity of histones to play the role of
      cofactor is less evident in the case when they are preincubated with DNA or
      cardiolipin. The interaction of natural antibodies with histones can explain
      their polyspecificity in some cases.

PMID- 9024985
TI  - Markers of type D retroviruses in children with Burkitt's-type lymphoma.
AB  - Antibodies to gag-coded proteins of type D retroviruses have been detected in
      children with lymphadenopathy [1]. We tested 41 HIV noninfected children with
      lymphoproliferative diseases (27 cases of Burkitt's-type lymphoma, six cases of
      Hodgkin's disease, four cases of T-cell lymphoma, three cases of lymphoblastic
      lymphoma and one case of large-cell anaplastic lymphoma) for the presence of type
      D retroviral serological and genetical markers. Twenty-five healthy donors were
      tested as a control. DNA samples from peripheral blood lymphocytes were analyzed
      by the polymerase chain reaction (PCR) and Southern blotting for the presence of
      type D retroviral related sequences. MPMV pro-pol specific sequences have been
      detected in 18 out of 27 children with Burkitt's-type lymphoma. By means of
      Western blotting, six patients positive in PCR/Southern blotting analysis were
      also found to contain Mason-Pfizer monkey virus (MPMV) specific antibodies, in
      their sera. All children with other lymphoproliferative diseases as well as
      healthy donors were negative in PCR/Southern blotting and Western blotting
      analysis. These data suggest the possible association of type D retroviral
      markers with Burkitt's-type lymphoma of children.

PMID- 9024986
TI  - CD8+ cells in HIV infection produce macrophage inflammatory protein-1 alpha and
      RANTES: a comparative study in long-term survivors and progressor patients.
AB  - Evidence suggests that CD8+ lymphocytes are involved in the control of Human
      Immunodeficiency virus type 1 (HIV-1) infection by the release of HIV-suppressive
      factors. The human chemokines RANTES and the macrophage inflammatory protein 1
      alpha (MIP-1 alpha) have been identified to be potent inhibitors of HIV in vitro.
      The aim of this study was to determine whether high levels of these chemokines
      are associated with a delayed progression of HIV disease. We have therefore
      analysed the in vitro production of RANTES and MIP-1 alpha from purified
      stimulated CD8+ cells from HIV+ long term survivors (LTS) and, as a comparison,
      from HIV+ patients with progressive disease. RANTES production was similar in LTS
      and progressors (14.06 +/- 3, 13.36 +/- 4.1 ng/ml, not statistically
      significant); the same cells from healthy controls show a RANTES production of 20
      +/- 3.5 ng/ml (P = 0.034 versus LTS and P = 0.038 versus progressors). MIP-1
      alpha production was slightly reduced in LTS (96.8 +/- 12 ng/ml) and progressors
      (91.6 + 17, not statistically significant between the two groups) when compared
      to healthy controls (109 +/- 7 ng/ml, P = 0.03). Our study suggests that
      resistance to HIV-1 progression in LTS may not be associated with high levels of
      RANTES and MIP-1 alpha production.

PMID- 9024987
TI  - The NF-kappa B inhibitor, tepoxalin, suppresses surface expression of the cell
      adhesion molecules CD62E, CD11b/CD18 and CD106.
AB  - Tepoxalin, a dual enzyme inhibitor of cyclooxygenase and 5-lipoxygenase has been
      shown to inhibit T-cell activation. Its immunosuppressive property is distinct
      from cyclosporin because only tepoxalin, but not cyclosporin, suppresses NF-kappa
      B activation. Here we report that tepoxalin selectively inhibits intercellular
      adhesion molecule-1 (ICAM-1, CD54)/MAC-1 (CD11b/CD18) dependent adhesion of
      polymorphonuclear cells to IL-1 activated human umbilical vein endothelial cells.
      The mechanism of inhibition is related to the surface expression of several cell
      adhesion molecules. Flow cytometry analyses on cultured cells that were treated
      with tepoxalin or antisense oligonucleotides to the P65/p50 subunit of NF-kappa
      B, and then stimulated with PMA, revealed a reduced expression of CD11b/CD18 on
      monocytic HL60 cells, and endothelial adhesion molecule-1 (CD62E) and vascular
      adhesion molecule-1 (CD106) on human umbilical vein endothelial cells. Expression
      of other adhesion molecules such as lymphocyte function associated-antigen-1
      (CD11a/CD18) and CD54 were unaffected. Tepoxalin also inhibited the secretion of
      a NF-kappa B regulated chemokine, IL-8, a known inducer of CD11b/CD18 expression.
      Thus the suppression of CD11b/CD18 expression by tepoxalin may involve IL-8. Our
      results suggest that by inhibiting NF-kappa B activation, surface expression of
      several adhesion molecules can be modulated and that tepoxalin may be useful in
      treating selected adhesion mediated events such as leukocyte migration or
      atherosclerotic plaque formation.

PMID- 9024989
TI  - Adhesion properties of human alveolar macrophages with respect to extracellular
      matrix components and chemotactic agonists.
AB  - Adherence has an essential impact on the differentiation and activation of tissue
      dwelling monocytes/macrophages. We have considered the effect of selected
      chemotactic agonists (fMLP, RANTES, IL-8) on the adhesion properties of human
      alveolar macrophages prepared by bronchoalveolar lavage. The macrophages were co
      incubated in buffer alone or buffer supplemented with respective agonist, for
      different time points, in culture wells precoated with albumin, vitronectin and
      fibronectin, respectively. The macrophages displayed a gradual increase in
      adhesion in all three surfaces and discriminated between the different matrix
      components, but did not respond to the selected agonists with increased adhesion.

PMID- 9024988
TI  - Enhanced TNF alpha production by monocytic-like cells exposed to dengue virus
      antigens.
AB  - The studies indicating the importance of TNF alpha in dengue virus infection have
      led us to determine whether monocyte-like cells produce TNF alpha exposure after
      dengue virus. The supernatant fluids of mosquito cells (AP61) infected with
      dengue virus (DV) type 1 and DV type 3 were harvested 7 days post-infection and
      clarified. DV inactivation was performed in the presence of betapropiolactone
      that preserves antigenicity of viruses. We used the monocytic-like cell line THP
      1 that is a model system of TNF alpha production. Polymyxin B (50 micrograms/ml)
      was added to block untoward effects resulting from possible LPS contamination of
      media or cultures. THP-1 cells were primed with a phorbol ester (PMA) for 24 h,
      then they were cultured for 4 and 24 h in the presence of inactivated culture
      supernatant of dengue infected AP61 cells or control preparations. The
      concentrations of TNF alpha in the culture supernatants were measured by using an
      immunoenzymatic assay. PMA-treated THP-1 cells rapidly secreted TNF alpha in
      response to inactivated culture supernatant of DV-infected cells. We found high
      levels of TNF alpha with cells exposed to DV1 and DV3 preparations compared with
      controls (mean values; 465 and 829 vs. 70 pg/ml, respectively, at 24 h post
      exposure, n = 4). We obtained a substantial inhibition of the enhancing activity
      of DV1 and DV3 infected supernatants in the presence of dengue hyperimmune mouse
      ascitic fluids. Our results demonstrate that exposure of monocytes/macrophages to
      DV particles or virus proteins derived from DV may be responsible for the
      enhanced production of TNF alpha in DV-infected patients.

PMID- 9024990
TI  - Synergistic effect of prolactin on IFN-gamma-mediated growth arrest in human
      monoblastic cells: correlation with the up-regulation of IFN-gamma receptor gene
      expression.
AB  - Interferon-gamma (IFN-gamma) stimulates the development of monocytic features in
      human myeloid precursors. Because transcriptional regulation of IFN-gamma and the
      pituitary hormone prolactin (PRL) has been described to involve common Jak-STAT
      pathways, we addressed here the question of whether PRL plays a role in
      monoblastic (U937) cell growth and macrophage maturation. In contrast to IFN
      gamma, PRL did not affect U937 cell growth nor induction of differentiation as
      assessed by the unchanged cell surface expression of maturation markers CD11b and
      HLA-DR class II. However, PRL in synergy with IFN-gamma inhibited, in a time- and
      dose-dependence, proliferation of U937 cells without influencing their maturation
      induced by IFN-gamma. IFN-gamma and PRL both affected the expression of the IFN
      gamma receptor (IFN-gamma R) gene by increasing IFN-gamma R mRNA levels. The rise
      in IFN-gamma R transcripts was accompanied by a low but significant release of IL
      6 which has previously been shown to stabilize IFN-gamma R mRNA. Moreover, a
      transient increase in surface expression of IFN-gamma R was observed in U937
      cells treated by IFN-gamma alone or in combination with PRL, whereas no apparent
      modulation of cell surface IFN-gamma R was observed in cells treated with PRL.
      Lastly, PRL did not induce transcriptional activation in IFN-gamma inducible IRF
      1 and Fc gamma RI genes in U937 cells. Together, our data indicate that IL-6
      secretion and increased expression of the IFN-gamma R gene correlate with U937
      cell growth arrest induced by IFN-gamma and PRL, probably through a signaling
      mechanism which does not involve the Stat 1/IRF-1 pathway.

PMID- 9024991
TI  - Pentoxifylline inhibits tumor necrosis factor alpha-induced priming of human
      neutrophils.
AB  - The study was designed to study the effect of pentoxifylline PTX on the
      chemiluminescence responses of neutrophils and on tumor necrosis factor-alpha
      (TNF-alpha)-induced priming of neutrophils. The results demonstrate that TNF
      alpha stimulated the respiratory burst by neutrophils and primed them for
      enhanced response to fMLP but not to PMA. The effect of TNF-alpha on the oxygen
      metabolism of neutrophils was inhibited when cells were treated with PTX. This
      reaction was dose-dependent. Additionally, the inhibiting influence of PTX on the
      chemiluminescence response of neutrophils was observed.

PMID- 9024992
TI  - Rapid determination of gamma delta T-cell stimulation by microfluorimetry.
AB  - Activated T-cell express CD25, the p55 chain of the IL-2 receptor. Here we report
      a reliable procedure for rapid determination of human gamma delta T cell
      activation by microfluorimetric measurement of CD25. Three days after initiation
      of culture, CD25 expression was determined. The sensitivity of this detection
      method was compared with [3H]thymidine incorporation at day 8. This proliferation
      assay allowed 3-5-fold higher dilution of the stimulatory ligand. However,
      monitoring of CD25 expression speeded up screening by 5 days. Therefore, for
      rapid screening of gamma delta T cell stimulation, e.g. for identification of
      activating ligands, monitoring of CD25 at day 3 is superior to [3H]thymidine
      measurement.

PMID- 9024994
TI  - A comparison of the inhibitory effect of cromoline and nedocromil Na on histamine
      release from airway metachromatic cells and from peripheral basophils.
AB  - Metachromatic cells are increased in the airways of asthmatic patients. We
      obtained metachromatic cells from asthmatic airways using an induced sputum
      technique. The histamine release following ConA, anti-IgE and anti-IgE + IL3 from
      those cells were evaluated before and following the addition of cromoline Na and
      nedocromil Na. Metachromatic cells had a higher rate of spontaneous histamine
      release when compared to peripheral basophils. Cromoline Na and nedocromil Na
      inhibited histamine release from triggered metachromatic cells but not from
      peripheral basophils. It is concluded that airway metachromatic cells from
      asthmatics behave differently than peripheral basophils.

PMID- 9024993
TI  - Modulation of antibody-forming cell and mitogen-driven lymphoproliferative
      responses by dietary nucleotides in mice.
AB  - Several studies have demonstrated that dietary nucleotides play a role in
      maintaining T-cell dependent immunity. In this work, we investigated the effects
      of nucleotide supplementation of a nucleotide-free diet (NFD) on some immunity
      parameters in BALB/c mice. Twenty day old mice were maintained on diets for 30
      days prior to use in experiments. The addition of nucleotide mixtures to NFD
      resulted in an increase in the response of hemolytic IgG-forming cells induced by
      previous immunization with sheep erythrocytes. When NFD was supplemented with
      single nucleotides, AMP, GMP, or UMP increased the IgG response, whereas CMP and
      IMP were without effect. GMP was the only nucleotide that increased the hemolytic
      IgM-forming cell response. Neither the contact hypersensitivity response to
      dinitrofluorobenzene nor the time of death after transplantation of a syngenic
      lymphoma was modified by nucleotide addition to NFD. The in vitro proliferative
      response of splenocytes to LPS was not affected by nucleotide supplementation of
      NFD, but the ConA-driven proliferative response was increased in mice fed NFD
      supplemented with nucleotide mixtures or with UMP. These data show that dietary
      mononucleotides stimulated at least some T-cell dependent immunity mechanisms.
      Moreover, these stimulatory effects may be obtained by supplementing a nucleotide
      free diet with a mixture in which mononucleotides are at the same levels as in
      murine breast milk.

PMID- 9024995
TI  - Systemic autoimmunity in LG/J mice.
AB  - Humoral and end-organ parameters of autoimmunity were investigated in LG/J mice,
      which have traditionally been considered normal, non-diseased animals.
      Surprisingly, LG/J mice were found to possess autoantibodies, including
      antinuclear antibodies and rheumatoid factor, and to develop renal disease,
      including glomerulonephritis, interstitial nephritis, and perivasculitis, but not
      hepatic or cutaneous disease. In contrast, age-matched, identically-housed
      control animals failed to develop autoantibodies or end-organ disease. These
      findings have complications for the genetic study of lupus erythematosus in the
      MRL murine model, which derives heavily from the LG/J background. Thus, the LG/J
      strain may provide a useful model in the analysis of autoimmunity.

PMID- 9024996
TI  - Conformation dependency of nitric oxide synthesis of murine peritoneal
      macrophages by beta-glucans in vitro.
AB  - We have already demonstrated that various activities including NO (nitric oxide)
      synthesis in vivo were significantly different between triple helical (SPG) and
      single helical (alkaline-treated SPG, SPG-OH) beta-glucans, and beta-glucan
      mediated NO synthesis was associated with increased gene of IFN-gamma. In this
      study, we analyzed beta-glucan-mediated NO production in vitro with the
      concomitant use of IFN-gamma. Proteose peptone-elicited peritoneal macrophages
      (PM) were collected from male C3H/HeJ mice and cultured with beta-glucans in the
      presence or absence of IFN-gamma for 24 h. It was found that SPG-OH, but not SPG,
      enhanced NO synthesis in vitro, especially in the presence of IFN-gamma.
      Concentrations of interleukin-1 alpha, -6 and TNF-alpha in the culture
      supernatant of SPG-OH were significantly higher than those in that SPG. Membrane
      associated IL-1 alpha was also high with SPG-OH. Cytokine productivity of PMs, as
      well as NO synthesis, was elevated in the presence of IFN-gamma. These facts
      intensely suggest that the single helical conformer of beta-glucan (SPG-OH) is
      dominant in cytokine production and subsequent NO synthesis.

PMID- 9025006
TI  - The angiotensin I-converting enzyme (ACE) locus is strongly associated with age
      and duration of diabetes in patients with type I diabetes.
AB  - We have investigated the frequency of the angiotensin I-converting enzyme (ACE)
      insertion/ deletion (I/D) polymorphism in 249 patients with type I diabetes and
      162 normal healthy controls. There was no significant difference in the frequency
      of ACE genotypes between those patients with diabetic nephropathy (n = 72)
      (nephropaths) compared to those with no proteinuria after 20 years duration of
      diabetes (n = 86) (normoalbuminurics). There was, however, a significant
      difference in the frequency of ACE genotypes between the short-duration and long
      term normoalbuminuric group (chi = 11.5, p = 0.001). Analysis of the ACE
      genotypes with respect to age and duration of diabetes showed that homozygosity
      for the insertion (I/I) genotype was significantly decreased with longer duration
      of diabetes (r2 = 92.7%, p < 0.009). No association was found with age in the
      normal controls. In conclusion, these results suggest that the ACE locus may be
      associated with longevity and survival in patients with type I diabetes rather
      than diabetic nephropathy or microvascular disease per se.

PMID- 9025007
TI  - Development of ischemic stroke in normotensive and hypertensive diabetic patients
      with or without antihypertensive treatment: an 8-year followup study.
AB  - Although the impact of hypertension as a risk factor for brain infarction in
      diabetes mellitus is evident, the beneficial effect of antihypertensive therapy
      has not been demonstrated. Therefore, we designed a prospective cohort study to
      elucidate the effects of antihypertensive therapy on the development of ischemic
      stroke in diabetic outpatients. Two hundred forty patients, 219 non-insulin
      dependent diabetes mellitus (NIDDM) and 21 insulin-dependent diabetes mellitus
      (IDDM), without history of cerebrovascular accident were followed for 8 years,
      from January 1981 until December 1988, in our diabetic clinic. Forty-eight of 88
      hypertensive patients had received antihypertensive drugs. Among 40 untreated
      hypertensive and 152 initially normotensive diabetics, 14 hypertensives and 11
      normotensives required antihypertensive therapy during followup period. Twenty
      three patients were dropped out because of the unidentified reasons.
      Cerebrovascular accident occurred in 24 patients (10%): 18 brain infarctions, 4
      transient ischemic attack (TIA), 1 subarachnoidal hemorrhage, and 1 brain
      hemorrhage. The percent incidence of ischemic strokes in the hypertension-treated
      patients was 8.9% which was similar to the 8.1% of the normotensives. In
      contrast, ischemic strokes developed in 29% of the untreated hypertensives, being
      significantly more frequent than in the former two groups. Multivariate analysis
      showed that serum total cholesterol and male gender were independent significant
      precursors of brain infarction in diabetic patients. In conclusion,
      antihypertensive treatment decreased the incidence of ischemic stroke in
      diabetics. Serum total cholesterol turned to independent risk factors for
      ischemic stroke in diabetic patients.

PMID- 9025008
TI  - Hypoglycemic symptom variation is related to epinephrine and not peripheral
      muscle sympathetic nerve response.
AB  - Hypoglycemic unawareness may be due to diminished adrenal and/or peripheral
      sympathochromaffin responses to hypoglycemia. To determine whether hypoglycemic
      symptom awareness is more closely related to adrenal or nonadrenal sympathetic
      activity, we studied the relationship between symptoms and the epinephrine,
      norepinephrine, and muscle sympathetic nerve activity (MSNA) responses to
      hypoglycemia in ten IDDM and ten control subjects. MSNA was measured continuously
      using microneurography during hyperinsulinemic (720 pmol m-2 min-1), glucose
      clamp with 60 min of euglycemia, 30 min of hypoglycemia, and 30 min of recovery.
      Subjects were asked to rate a series of symptoms every 10 min during the last 30
      min of each period and were unaware of their plasma glucose concentration. MSNA
      increased significantly in both groups during insulin clamp (p < 0.05) and
      further increased during hypoglycemia (p < 0.01). Both epinephrine and
      norepinephrine levels significantly increased during hypoglycemia (p < 0.02). The
      increase in adrenergic symptom responses during hypoglycemia positively
      correlated with epinephrine (r = 0.75, p < 0.01), but not with MSNA in the
      control subjects. A similar near significant relationship for epinephrine was
      seen in IDDM subjects (r = 0.65, p = 0.056). No significant predictors were found
      for neuroglycopenic or cholinergic symptoms. Thus, the variation in hypoglycemic
      symptoms is not related to the MSNA response to hypoglycemia. Adrenergic symptom
      variation is due to differences in adrenal epinephrine secretion.

PMID- 9025009
TI  - Cutaneous vasomotor responses in young type I diabetic patients.
AB  - Abnormal skin temperature reactions have been reported in type I diabetic
      patients. Whether this is due to a primary vascular disturbance or autonomic
      neuropathy is unclear. The aim of this study was to clarify this issue by
      evaluating cutaneous circulatory reactions before and after provocation.
      Seventeen type I diabetic patients and 17 age-matched controls were studied by
      recording blood flow (laser Doppler technique) on the dorsum of the hand (before,
      during, and after arterial occlusion), blood flow and skin temperatures on the
      dorsum of the foot and on the toe (before and after cooling followed by indirect
      body heating) and autonomic nerve function (heart rate reaction to deep breathing
      and to tilting). The results showed that before [4.6 +/- 0.5 perfusion units (PU)
      versus 6.1 +/- 0.7 PU; p = 0.0356] and after arterial occlusion (17.5 +/- 1.6 PU
      versus 25.3 +/- 1.7 PU; p = 0.0024), hand skin blood flow was significantly lower
      in patients than in controls. On the dorsum of the foot, skin temperatures was
      significantly lower in patients than in controls before cooling (29.2 degrees C
      +/- 0.3 degrees C versus 30.5 degrees C +/- 0.4 degrees C; p = 0.0107) whereas
      toe temperature and toe blood flow were similar before and after cooling in
      patients and controls. After body heating, however, toe temperature (after 30
      min: 25.2 degrees C +/- 1.4 degrees C versus 30.9 degrees C +/- 1.2 degrees C; p
      = 0.0022) and toe blood flow (after 30 min: 10.9 +/- 2.5 degrees C versus 22.9 +/
      4.9 PU; p = 0.0313) were significantly lower in patients than in controls,
      especially in patients with parasympathetic neuropathy (i.e., patients with
      abnormal heart rate reactions to deep breathing). In conclusion, type I diabetic
      patients demonstrated a vascular disturbance in their skin that seemed to be
      exaggerated by parasympathetic neuropathy.

PMID- 9025010
TI  - Diabetic peripheral neuropathy: effects of age, duration of diabetes, glycemic
      control, and vascular factors.
AB  - The aim of this study was to determine the factors associated with diabetic
      peripheral neuropathy and more particularly its relation to precisely assessed
      microangiopathy. Peripheral neuropathy was assessed in 135 diabetic patients: 28
      insulin-dependent diabetes mellitus (IDDM), 85 non-insulin-dependent diabetes
      mellitus (NIDDM), and 22 insulin-treated NIDDM patients, on the basis of both
      clinical findings and extensive electrophysiological testing (four motor nerves
      and four sensory nerves, and right and left Hoffmann's reflex), using a total of
      20 parameters. The percentage of women with severe clinical neuropathy was
      significantly higher than that of men, and the clinical neurological stage
      correlated significantly with age and duration of diabetes. According to
      multivariate analysis the clinical stage correlated only with gender and duration
      of diabetes. Several electrophysiological parameters were significantly more
      abnormal in women and correlated with age, type and duration of diabetes, and
      recent glycemic control. The multivariate analysis showed that 17
      electrophysiological parameters correlated with duration of diabetes, nine
      correlated with age, seven with glycemic control, and only one with gender. The
      presence of clinical neuropathy also correlated with presence of retinopathy,
      arterial hypertension, macroangiopathy, and biological signs of nephropathy. All
      the electrophysiological parameters were significantly more abnormal in patients
      with retinopathy or macroangiopathy than in patients without these complications.
      Separate parameter analysis showed that at least one abnormal
      electrophysiological parameter was almost always found in patients with
      retinopathy, macroangiopathy, or incipient nephropathy, but abnormalities were
      also found to a slightly lesser extent in patients without these complications.
      Multivariate analysis showed that when duration of diabetes, retinopathy,
      macroangiopathy, and biological signs of nephropathy were introduced into the
      model, 11 electrophysiological parameters correlated with duration of diabetes,
      11 with retinopathy, seven with macroangiopathy, and five with a sign of
      nephropathy. This study demonstrates that age and glycemic control have an
      effect, and diabetes duration a major effect on peripheral nerve function. It
      suggests that vascular factors may participate in the development of nerve
      lesions.

PMID- 9025011
TI  - Pulse oximetry for the assessment of autonomic neuropathy in diabetic patients.
AB  - Altered vascular responses to various thermal stimuli correlate well with the
      changes of autonomic neuropathy. These responses were assessed by the use of
      pulse oximetry. Standard cardiac autonomic function tests were performed in
      normal subjects (n = 12), diabetic patients without autonomic neuropathy (n = 8),
      and diabetic patients with autonomic neuropathy (n = 7). Autonomic functions in
      the same patients then were assessed by estimating the severity of vasospasm in
      response to cold stimulus with the help of pulse oximetry. Percentage fall in
      oxygen saturation at 15, 30, 60, 90, and 120 sec of exposure to cold stimulus was
      recorded on pulse oximeter. Time required for recovery and presence or absence of
      rebound rise following removal of cold stimulus were noted. In diabetics with
      autonomic neuropathy, the rate of fall in percentage oxygen saturation was
      significantly slower (p < 0.0001), less intense (p < 0.0001) and with delayed
      subsequent recovery (p = 0.013), compared to normal subjects. Rebound rise in
      oxygen saturation was absent in all the diabetics with autonomic neuropathy,
      compared to 2 of 12 normal subjects (p < 0.0001). We conclude that pulse oximetry
      may be a potentially useful, simple, and noninvasive bedside method for
      assessment of diabetic autonomic neuropathy.

PMID- 9025012
TI  - Cognitive function in elderly non-insulin-dependent diabetic patients before and
      after inpatient treatment for metabolic control.
AB  - Cognitive function was measured before and after inpatient treatment for
      metabolic control in 20 elderly patients with non-insulin-dependent diabetes
      mellitus (NIDDM). Another 20 patients still on the waiting list for this
      treatment, served as a control group. Glycosylated hemoglobin decreased in both
      groups. Psychomotor speed and concentration improved only after inpatient
      treatment (p < 0.01; p < 0.05, respectively). Improved performance was maintained
      and even enhanced 6 weeks after discharge from inpatient treatment. Performance
      in concentration tasks correlated with glycosylated hemoglobin (p < 0.05). It is
      concluded that cognitive deficits in elderly NIDDM patients can be reduced by
      inpatient treatment, although the benefit of glycemic control was not clearly
      demonstrated in this study.

PMID- 9025020
TI  - The efficacy of epidural anesthesia for endoscopic preperitoneal herniorrhaphy: a
      prospective study.
AB  - Laparoscopic herniorrhaphy has been criticized because of the need for general
      anesthesia. The endoscopic preperitoneal approach allows the use of epidural
      anesthesia, obviating the potential complications and side effects seen with
      general anesthesia. The purpose of this study was to determine the efficacy of
      epidural anesthesia for preperitoneal herniorrhaphy. Fifty-two patients underwent
      repair of a total of 80 hernias over a 6-month period. Thirty-six patients
      underwent their repairs with the use of epidural anesthesia with the goal of a T
      4 sensory level. A tension-free prosthetic repair was performed in all patients.
      Seventeen patients had unilateral repairs and nineteen had bilateral repairs
      under epidural, while seven patients had unilateral repairs and nine patients had
      bilateral repairs under general anesthesia. There were no significant differences
      in patient demographics. All herniorrhaphies were electively performed on an
      outpatient basis by a single surgeon (A.L.S.) in a teaching setting. There were
      no significant differences for unilateral and bilateral repairs when type of
      anesthesia was compared. There was only one conversion from epidural to general
      anesthesia, secondary to poor sensory blockade first noticed during creation of
      the preperitoneal space (97% success rate). Seven patients receiving epidural
      anesthesia experienced pneumoperitoneum during the procedure. This did not effect
      the ability to perform the hernia repair successfully. There were no
      complications related to the epidural anesthetic. Endoscopic preperitoneal
      herniorrhaphy can be performed effectively under epidural anesthesia, obviating
      the need for general anesthesia.

PMID- 9025013
TI  - Effects of diabetes on reactivity of sciatic vasa nervorum in rats.
AB  - The aim was to investigate the effects of 2 months of streptozotocin-induced
      diabetes mellitus in rats on the responses of sciatic vasa nervorum to vasoactive
      drugs. Changes in perineural blood flow were monitored by laser-Doppler flowmetry
      during drug superfusion in vivo. Laser-Doppler flux was reduced by 53.3% after 2
      months of diabetes. A 38-fold increase in norepinephrine sensitivity was found in
      diabetic compared to nondiabetic rats. Co-superfusion of norepinephrine and a
      high dose (100 microM) of the nitric oxide synthase inhibitor, NG-nitro-L
      arginine, resulted in 116-fold and 3.6-fold increases in norepinephrine
      sensitivity in nondiabetic and diabetic rats, respectively, such that dose
      response curves for changes in vascular conductance were superimposed. This
      suggests that the increased norepinephrine sensitivity in diabetes was caused by
      defective endothelial nitric oxide production or action. After norepinephrine
      preconstriction, acetylcholine caused dose-dependent increases in vascular
      conductance, sensitivity being 8.1-fold greater in nondiabetic than diabetic
      rats. In contrast, endothelium-independent responses to the nitrovasodilator,
      glyceryl trinitrate, were relatively unaffected by diabetes. Thus, diabetes
      causes a deficit in nitric oxide mediated endothelium-dependent relaxation of
      vasa nervorum, resulting in increased vasoconstrictor sensitivity which is likely
      to impair perfusion and contribute to the pathogenesis of neuropathy.

PMID- 9025021
TI  - Results of a prospective multicenter trial evaluating the ePTFE peritoneal onlay
      laparoscopic inguinal hernioplasty.
AB  - A 2.8-year prospective multicenter trial was conducted to evaluate the ePTFE
      peritoneal onlay laparoscopic inguinal hernioplasty. A total of 441 inguinal
      hernias were repaired in 351 patients (326 male; 25 female). Two hundred twenty
      six of the hernias were direct, 185 indirect, 4 femoral, 26 pantaloon, 90
      bilateral, and 92 recurrent. Standardized data collection forms were used and
      submitted for centralized data analysis. For the hernioplasty, Cooper's ligament
      was exposed and an 8 cm x 12 cm x 1 mm GORE-TEX Soft Tissue Patch was stapled
      circumferentially to Cooper's ligament and the endoabdominal fascia. Patients
      were followed at 1 week, 6 months, 1 year, and then annually. Three-month
      intervals were used as needed. There was a mean follow-up of 447 days, with 21%
      of the total repairs followed for more than 2 years and 56% for more than a year.
      The overall follow-up rate was 95.5%. The operative and postoperative
      complication rates were 0.45% and 8%, respectively. There were 17 recurrent
      hernias (3.8%). The range of experience among the investigators was 13 to 168
      hernioplasties. With the completion of 25 cases per investigator, the recurrence
      rate fell to 0.39%. Postoperative analgesia averaged a 24-hr supply of
      medication; 12.2% of patients required no analgesia. Convalescence averaged 5.4
      days, and return to work averaged 7.7 days. This multicenter trial demonstrates
      that the ePTFE laparoscopic peritoneal onlay inguinal hernioplasty is a safe and
      dependable repair, especially after the initial learning curve is surmounted.

PMID- 9025022
TI  - Laparoscopic treatment of nonparasitic cysts of spleen and liver.
AB  - Laparoscopic treatments of nonparasitic splenic and liver cysts in the period
      between March 1993 and April 1995 have been reported: partial decapsulation
      fenestration and evacuation of a splenic pseudocyst in one patient, fenestration
      of large congenital liver cysts with total excision of a few smaller liver cysts
      in two patients and two unsuccessful treatments of splenic cysts. After
      successful laparoscopic procedures the patients experienced immediate and
      complete relief of the symptoms. Two years after the splenic cyst procedure and 6
      months after the liver cyst operation, the patients remained free of the
      symptoms, and complete absence of the cysts was confirmed by computerized
      tomography scans. Laparoscopic fenestration of nonparasitic splenic and liver
      cysts with total excision of smaller liver cysts is a simple and safe surgical
      method with lower morbidity and a quick return to normal activity.

PMID- 9025023
TI  - Morbidity and mortality of laparoscopic cholecystectomy in an institutional
      setup.
AB  - Laparoscopic cholecystectomy (LC) though a very safe operative procedure does
      have its own morbidity and mortality. The present study was undertaken to analyze
      the morbidity and mortality of this procedure in an institutional setting.
      Between October 1992 and October 1995 a total of 433 patients received LC.
      Conversion to open cholecystectomy was required in 62 patients (14.3%). The
      decision to convert was made because the surgeon was forced to convert (3.7%) or
      the conversion was the operator's choice (10.6%). There was no difference in the
      conversion rate of consultants versus residents (14.4% vs. 14.2%). Major
      intraoperative and postoperative morbidity was encountered in 8.3% of patients.
      One patient required reexploration. The incidence of common bile duct (CBD)
      injury was 2.5%. There was no operative or 30 days mortality. However, two
      patients died in the follow-up period due to procedure-related complications. Low
      threshold for conversion, early recognition of morbidity, and prompt and
      judicious management of such complications under guided supervision is necessary
      in order to avoid major postoperative problems. The experience in a teaching
      hospital training program is different from that of an individual surgical setup.

PMID- 9025024
TI  - Vaginal appendectomy at laparoscopic-assisted vaginal hysterectomy: a surgical
      option.
AB  - This report demonstrates the use of the laparoscope as a means of selecting and
      facilitating cases of incidental appendectomy by the vaginal route in 12 patients
      undergoing laparoscopic-assisted vaginal hysterectomy. The procedure was
      performed successfully in all cases, required an average of 12 min additional of
      operating time, and was not accompanied by intraoperative or postoperative
      complications. Our preliminary experience suggests that in selected cases,
      laparoscopic-assisted transvaginal appendectomy is a simple, cost-effective
      alternative to laparoscopic appendectomy.

PMID- 9025025
TI  - Laparoscopic radical prostatectomy in the canine model.
AB  - The purpose of this study was to determine the feasibility of performing
      laparoscopic radical prostatectomy in a canine model. Laparoscopic radical
      prostatectomy was performed on six adult male canines. A new endoscopic needle
      driver was used to construct a secure vesicourethral anastomosis. Average
      operative time required to complete the procedure was 304 min (range 270-345
      min). Dissection of the prostate gland took an average of 67 min (range 35-90
      min), and construction of the vesicourethral anastomosis took 154 min (rage 80
      240 min). There were no intraoperative complications and only one postoperative
      complication (anastomotic leak). Five of the six animals recovered uneventfully
      from the procedure, and their foley catheters were removed 10-14 days
      postoperatively after a retrograde cystourethrogram demonstrated an intact
      vesicourethral anastomosis. Four (80%) of the surviving animals were clinically
      continent within 10 days after catheter removal. Post mortem examination
      confirmed that the vesicourethral anastomosis was intact with no evidence of
      urine extravasation. These data demonstrate the feasibility of laparoscopic
      radical prostatectomy in a canine model, and suggest that additional work with
      this technique should be continued to develop its potential clinical application.

PMID- 9025026
TI  - Laparoscopic common bile duct exploration: a review.
AB  - The use of laparoscopic methods to explore the common bile duct is now well
      established, although they continue to undergo continuous evolution and
      improvement. In experienced hands laparoscopic management of choledocholithiasis
      may be undertaken with morbidity and mortality at least as good as that of open
      surgery. The use of diagnostic endoscopic retrograde cholangiopancreatography
      (ERCP) with or without sphincterotomy before or after laparoscopic intervention
      must be evaluated. The degree of acceptance that laparoscopic techniques for
      common bile duct exploration (CBDE) will achieve within the surgical community
      remains to be determined, but will likely increase as more practicing surgeons
      familiarize themselves with them.

PMID- 9025027
TI  - Saint's triade presenting as volvulus of the gallbladder.
AB  - Saint's triade of hiatus hernia, colonic diverticula, and cholelithiasis
      presenting with volvulus of the gallbladder is a unique occurrence. Possible
      etiology of volvulus of the gallbladder involves kyphosis, viceroptosis,
      cholelithiasis, and in this case adhesive bands. Laparoscopic decompression of
      the gallbladder, division of the adhesive bands, detorsion of the volvulus, and
      finally laparoscopic cholecystectomy successfully resolved this uncommon clinical
      problem. We describe a case and review the literature.

PMID- 9025028
TI  - Hernia of the lung repaired by VATS: a case report.
AB  - Hernia of the lung is an uncommon clinical entity. The majority of reported
      hernias are acquired traumatic thoracic hernias. A case of an acquired
      spontaneous hernia occurring through an old anterior thoracotomy scar is
      presented. We believe pathogenesis of this hernia was the result of increased
      intrathoracic pressure secondary to tracheobronchomegaly and anterior-posterior
      collapse of the trachea during expiration. The hernia was successfully repaired
      by a video-assisted thoracic surgical (VATS) technique using prolene mesh and a
      hernia stapler similar to the technique used in repair of an inguinal hernia.

PMID- 9025029
TI  - Laparoscopic treatment or a nonparasitic splenic cyst: case report.
AB  - The authors describe a case of nonparasitic splenic cyst treated by laparoscopic
      fenestration. The patient complained of left upper quadrant pain that increased
      during the prior 3 months. Computed tomography scan revealed a large cyst of the
      inferior pole of the spleen. The patient was submitted to laparoscopic wide
      fenestration of the cystic wall. The postoperative course was unremarkable and
      the patient was discharged with complete relief of symptoms. Laparoscopic
      technique provides the same results in terms of effectiveness and safety as
      traditional surgery, linked to the benefits of the mininvasive approach; thus,
      the laparoscopic fenestration can be considered the ideal treatment of
      nonparasitic splenic cysts.

PMID- 9025030
TI  - Diagnostic laparoscopy for dog bite wounds to the abdomen.

PMID- 9025032
TI  - Current and future treatment of carotid bifurcation atherosclerotic disease: a
      perspective.

PMID- 9025033
TI  - Pedal arterial imaging.

PMID- 9025034
TI  - Stent-graft repair of aorto-iliac occlusive disease coexisting with common
      femoral artery disease.
AB  - PURPOSE: Significant disease or occlusion of the common femoral artery may
      preclude percutaneous therapy for aorto-iliac occlusive disease. In addition,
      aorto-iliac angioplasty may not reverse the ischemic symptoms when common femoral
      artery disease exists. The authors describe the feasibility of endoluminal stent
      grafts to treat multilevel aortoiliofemoral occlusive disease. MATERIALS AND
      METHODS: The authors placed 18 stent-grafts for aorto-iliac occlusive disease in
      17 patients with limb-threatening ischemia and significant common femoral artery
      disease. These procedures were performed as a joint effort between vascular
      surgery and interventional radiology staff in the operating room. The common
      femoral artery was occluded in 10 or severely diseased in eight, necessitating
      endoluminal bypass to the superficial femoral or popliteal artery (n = 7) or to
      the deep femoral artery (n = 7), or necessitating patch angioplasty of the common
      femoral artery (n = 4). Stent-grafts were fabricated from 6-mm
      polytetrafluoroethylene and 29-mm Palmaz stents. RESULTS: All 18 grafts were
      placed successfully. Follow-up ranged from 3 to 38 months (mean, 21 months).
      Seven patients died of myocardial infarction; two grafts occluded and one
      required angioplasty during follow-up, resulting in a primary patency rate of 81%
      at 2 years. CONCLUSION: Endoluminal stent-graft placement is a useful method of
      treatment for advanced atherosclerotic aorto-iliac disease, particularly in the
      presence of common femoral artery disease. This approach avoids an extra-anatomic
      bypass or a major transabdominal aortic bypass procedure. Longer follow-up with a
      larger series is needed to ensure the safety and late graft patency comparable to
      the traditional aortofemoral and iliofemoral bypass grafts.

PMID- 9025035
TI  - Use of a self-expanding vascular occluder for embolization during endovascular
      aortic aneurysm repair.
AB  - PURPOSE: Repair of aortic aneurysms with use of stent-graft techniques may
      require occlusion of large branch vessels to prevent back-bleeding into the
      excluded aneurysmal sac. The authors describe their experience using a self
      expanding vascular occluder (SEVO) to occlude flow in branch arteries during
      aortic stent-grafting. PATIENTS AND METHODS: Eighty-four patients (65 men, 19
      women; mean age, 64 years) underwent thoracic (n = 72) or abdominal aortic (n =
      12) stent-grafting. Aneurysm repair was performed using nonbifurcated Z stents
      covered with polyester or polytetrafluoroethylene (PTFE) fabric. SEVOs
      constructed from a Z stent (10-20 mm diameter) and PTFE were deployed through a
      separate catheter (14-20 F). RESULTS: Ten of 84 patients required embolization of
      large branch arteries with use of a SEVO during aortic stent-grafting (thoracic,
      n = 1; abdominal, n = 9). The SEVO was placed in the common iliac (n = 9) or
      subclavian artery (n = 1). The mean SEVO diameter was 14.7 mm (range, 10-20 mm).
      Eight patients undergoing SEVO embolization had immediate thrombosis of the
      treated artery. One patient required additional embolization with use of
      conventional coils. No patients had back-bleeding into the aneurysm, device
      migration, microembolization, or limb ischemia (mean follow-up, 140 days; range,
      50-200). All 10 patients had complete thrombosis of the aortic aneurysm.
      CONCLUSION: Use of a novel self-expanding vascular occluding device is a safe and
      effective supplementary technique to occlude high-flow, large-diameter arterial
      branch vessels during endovascular aortic aneurysm repair.

PMID- 9025036
TI  - Aortoesophageal fistula: repair with transluminal placement of a thoracic aortic
      stent-graft.

PMID- 9025037
TI  - Inflammatory aneurysm treated by means of transfemoral endovascular graft
      insertion.

PMID- 9025038
TI  - Natural history of arterial injuries diagnosed with arteriography.
AB  - PURPOSE: To evaluate the natural history of untreated arterial injuries
      identified at arteriography. MATERIALS AND METHODS: The medical charts and
      radiographs were reviewed for all patients with arterial injuries identified
      during arteriography who were managed by means of nonoperative observation and
      underwent follow-up arteriography. RESULTS: Eighty-six nonrandomized patients
      with 105 arterial injuries were identified. These included 33 narrowed segments,
      two dilated segments, 23 intimal defects, 13 occlusions, 12 false aneurysms, 13
      arteriovenous fistulas (AVFs), and five extravasations. Four vessels initially
      considered normal were subsequently found to have injuries. The average duration
      of observation was 23.5 days (range, 1-1,900 days). Forty-two arterial
      abnormalities healed spontaneously without other intervention. Thirty-eight
      "minimal" injuries improved or healed, whereas 25 worsened. Thirteen transmural
      injuries improved, whereas 12 progressed. There was no significant morbidity or
      mortality due to the delay involved with sequential studies. CONCLUSIONS: The
      natural history of these abnormalities was variable and unpredictable.
      Nonocclusive "minimal" injuries rarely cause ischemic or hemorrhagic
      complications. Although symptomatic AVFs have a low probability of spontaneous
      resolution, asymptomatic lesions may close and the risks associated with a few
      months of observation are minimal. Close follow-up is essential if a nonoperative
      approach is undertaken.

PMID- 9025039
TI  - Percutaneous transluminal stent placement in the abdominal aorta.
AB  - PURPOSE: To retrospectively review and to report the results of stent placement
      for focal mid-abdominal aortic stenoses. MATERIALS AND METHODS: During a 4-year
      period, 10 focal mid-abdominal aortic stenoses were treated with stent placement
      in nine patients (six women and three men; mean age, 61 years; range, 49-73
      years). All of the stenoses were atherosclerotic in nature except for one at the
      proximal anastomosis of an aortobi-femoral graft, which may have been from
      fibrointimal hyperplasia. Seven of the 10 stenoses were treated with primary
      stent placement, whereas three were treated with stent placement after suboptimal
      angioplasty. RESULTS: The technical success rate was 100%. Clinical success,
      defined as complete elimination or improvement of symptoms present before stent
      placement, was achieved in eight of the nine patients with a mean duration of
      follow-up of 1.6 years (range, 0.2-3.0 years). CONCLUSION: In view of the
      excellent technical and clinical success, the authors believe that stent
      placement should be considered as an adjective therapy to angioplasty or as a
      primary method of treatment in properly selected patients with focal mid
      abdominal aortic stenoses.

PMID- 9025040
TI  - Placement of inferior vena caval filters in the intensive care unit.

PMID- 9025041
TI  - Superselective bronchial artery embolization for hemoptysis with a coaxial
      microcatheter system.
AB  - PURPOSE: To compare the effectiveness and safety of superselective bronchial
      artery embolization with that of nonsuperselective embolization in the control of
      hemoptysis. MATERIALS AND METHODS: Retrospective case analysis was done for 47
      patients with hemoptysis originating from a variety of causes. In 22 patients,
      embolization was performed superselectively using a microcatheter inserted into
      the bronchial artery beyond the spinal or mediastinal branches (superselective
      group). In the remaining 25 patients, embolization was performed at the opening
      of the bronchial artery with a 5-F catheter (nonsuperselective group). RESULTS:
      Initial hemoptysis control rates were 96% (21 of 22) in the superselective group
      and 88% (22 of 25) in the nonsuperselective group. Cumulative hemoptysis control
      rates of the superselective and nonsuperselective groups were 80% and 67% at 6
      months, 79% and 56% at 1 and 2 years, and 79% and 48% at 3 years, respectively
      (not significant; generalized Wilcoxon test). One major complication (spinal
      infarction) occurred in the nonsuperselective group. CONCLUSIONS: Superselective
      embolization is safer and more effective way to control hemoptysis than the
      ordinary (nonsuperselective) method.

PMID- 9025043
TI  - You are asked to place a dialysis access catheter in a patient. What is your
      preferred access site, and why?

PMID- 9025042
TI  - Spiral basket for percutaneous embolectomy of the infrageniculate popliteal
      artery.

PMID- 9025044
TI  - Aortic stents covering the renal arteries ostia: an animal study.
AB  - PURPOSE: To evaluate the consequences of placing an aortic stent over the renal
      arteries. MATERIALS AND METHODS: The renal ostia of 11 pigs were covered by
      Strecker stents placed in the aorta. At 1 month, the degree of renal ostial
      stenosis was determined by means of angiography and gross pathologic and
      histologic examination. Any reduction in area of the renal ostia was considered
      significant. Preprocedure and 1-month serum creatinine levels were also examined.
      RESULTS: One stent migrated and was excluded from the study. There was one
      angiographic failure and, among the remaining 18 renal arteries evaluated, one
      was occluded, six were stenosed, and 11 were patent. Of the 10 samples available
      for pathologic examination, one was excluded from study because one stent was not
      fully deployed. A neointima was covering the struts crossing or encircling the
      renal arteries ostia with a mean area coverage of 43% +/- 30% (range, 0-84%).
      Serum creatinine levels rose from 71.1 mumol/L +/- 7.1 preoperatively to 94.2
      mumol/L +/- 6.7 postoperatively (P < .01). CONCLUSION: An aortic stent placed
      over the renal arteries in pigs may compromise renal perfusion in the long-term
      because neointima tends to fill the spaces between the struts.

PMID- 9025045
TI  - Human aortic endothelial cell migration onto stent surfaces under static and flow
      conditions.
AB  - PURPOSE: The objective of the present study is to establish an in vitro model
      designed to quantitatively define human aortic endothelial cell (HAEC) migration
      onto stainless steel stent material under both static and flow conditions of high
      and low wall shear stress. MATERIALS AND METHODS: To simulate implantation of a
      stent onto the intact arterial wall, HAECs were seeded and grown to confluence on
      thick, firm collagen gels. Flat 1 x 1-cm square, stainless steel pieces were
      implanted on this endothelialized surface and migration of HAECs onto the steel
      surface was monitored, measured, and compared under static and high (15
      dynes/cm2) and low (2 dynes/cm2) wall shear stress flow conditions designed to
      model wall shear stress levels encountered at different sites within the human
      arterial system. RESULTS: Under no flow, endothelial cell migration occurred
      uniformly from the periphery, attaining complete confluence over the square
      surface within 14 days. The initial migratory rate was approximately 10
      micrograms/h +/- 0.5 days 1-3 and increased to a rate near 15 micrograms/h +/-
      0.5 between days 10 and 14. High shear stress significantly (P < .002) increased
      HAEC migration rate to 25 micrograms/h +/- 0.8 in the direction of flow,
      resulting in an increase in total area endothelial coverage from 59% under no
      flow to 87% under high shear stress flow conditions when compared at 7 days.
      CONCLUSIONS: These results indicate the rate and extent of endothelial migration
      onto a prosthetic material surface are influenced by the level of direction of
      flow-related wall shear stress. Furthermore, these results demonstrate an in
      vitro model that provides a method to quantitatively evaluate and possibly
      predict the relative ability of different prosthetic materials to endothelialize
      under variable in vivo flow conditions.

PMID- 9025046
TI  - MR microscopy of the arterial wall in an experimental model of atherosclerosis:
      preliminary results.
AB  - PURPOSE: To obtain images of the arterial lumen and wall in a rabbit model of
      atherosclerosis with use of high-resolution magnetic resonance (MR) imaging to
      follow morphologic changes during the induction of atherosclerosis and, hence,
      develop a non-invasive tool to investigate restenosis. MATERIALS AND METHODS: In
      vivo microscopic MR images of rabbit aorta were acquired after balloon injury.
      Measurements of wall and lumen diameter from MR images area were compared with
      measurements obtained from histologic and angiographic examination. RESULTS:
      Injured rabbits exhibited an obvious thickening of the arterial wall, accompanied
      by an increased wall conspicuity, probably due to increases in T2. Quantitative
      MR morphometry corresponded well with morphologic measurements based on
      angiographic and histologic study. CONCLUSIONS: MR implanted coil technology
      affords imaging of the arterial lumen and wall, allowing temporal assessment of
      the morphologic changes due to intimal hyperplasia after balloon dilation and may
      enable the evaluation of novel techniques to eliminate restenosis.

PMID- 9025047
TI  - Prototype stent: in vivo swine studies in the biliary system.
AB  - PURPOSE: To evaluate the safety of implantation and the biocompatibility of a new
      balloon-expandable stent in the biliary system of the swine model. MATERIALS AND
      METHODS: Thirty stents, varying in diameter from 4 mm to 12 mm and in length from
      2 cm to 6 cm, were placed in the bile ducts of 10 microswine. After implantation,
      one-third of the animal subjects were killed at 2 months and the rest, at 6
      months. All animals underwent premorbid cholangiography. Stents were pressure
      fixed, harvested, and encased in methacrylate. Specimens were then sectioned with
      a diamond saw, prior to staining. Individual specimens were photographed for
      visualization of the histologic reaction. RESULTS: Technical success
      (implantation) was 100%. All stents were widely patent at 2-month and 6-month
      follow-up. Histopathologic study demonstrated a very thin epithelial hyperplasia
      that formed between stent wires. This did not cover the stent wires. CONCLUSION:
      This new stent is safely implantable and demonstrates minimal tissue reaction in
      the biliary system of the swine, when compared with other metallic biliary
      stents.

PMID- 9025048
TI  - Vascular stent prototype: in vivo swine studies.
AB  - PURPOSE: Evaluation of implantation technique and biocompatibility of a new
      balloon-expandable peripheral vascular stent. MATERIALS AND METHODS: Twenty-four
      stents, varying in diameter from 4 mm to 14 mm and length from 2 cm to 6 cm, were
      placed in eight microswine. After implantation, two of the animals were killed at
      2 months and the remaining animals were killed at 6 months. All animals underwent
      premorbid angiography. The stents were then pressure fixed, harvested, and
      encased in methacrylate. The specimens were then sectioned by a diamond saw prior
      to staining. Individual specimens were then photographed, projected against a
      screen, and the neointimal thickness quantified by calibration with the diameter
      of the stent wire retained in the specimen. RESULTS: Technical success
      (implantation) was 96% (one embolization). All stents were widely patent at 2-
      and 6-month follow-up. Histopathologic examination demonstrated a very thin
      neointima covering the stent wires, with a maximum thickness measuring 254
      microns. CONCLUSION: This new stent is safely implantable and biocompatible as
      tested in the arterial system of this animal model. Human clinical trials are
      indicated.

PMID- 9025049
TI  - Experimental nonsurgical transcervical sterilization with a custom-designed
      platinum microcoil.
AB  - PURPOSE: Investigation of a technique for nonsurgical female sterilization.
      MATERIALS AND METHODS: A custom designed platinum microcoil with Dacron fibers
      was placed unilaterally into a fallopian tube and uterine horn of 10 rabbits
      after transcervical selective tubal catheterization with use of fluoroscopic
      guidance. The contralateral uterus and fallopian tube served as controls. After
      the rabbits were bred, pregnancy was determined by palpation and confirmed at
      autopsy. Postmortem histopathologic evaluation of uteri and fallopian tubes was
      performed. RESULTS: Nine of the 10 rabbits became pregnant. None of the animals
      had embryos on the microcoil side. Nine rabbits had a total of 45 embryos on the
      control side. One animal failed to become pregnant on either side. The microcoil
      remained in good position in all 10 rabbits. There was a microcoil-associated,
      mild inflammatory tissue response in the uteri and fallopian tubes. CONCLUSION: A
      platinum occlusion microcoil placed in a utero-tubal location has potential as a
      means for nonsurgical female sterilization.

PMID- 9025050
TI  - Saline injection into the perirectal space to assist transgluteal drainage of
      deep pelvic abscesses.

PMID- 9025051
TI  - Attempted induction of chronic portal venous hypertension with polyvinyl alcohol
      particles in swine.
AB  - PURPOSE: Creation of presinusoidal chronic portal venous hypertension by means of
      repeated portal vein (PV) embolization was explored in an attempt to improve a
      porcine model of transjugular intrahepatic portosystemic shunt (TIPS) patency.
      MATERIALS AND METHODS: Six microswine underwent weekly PV embolization for 5
      weeks with a total of 10.4-12.6 g of polyvinyl alcohol (PVA) particles (0.149
      0.250 mm in size). Portography, liver function tests, pressure measurement in the
      PV and inferior vena cava (IVC) before and after PV embolization, and
      histopathologic evaluation of the livers were performed. RESULTS: Transhepatic
      portal venography performed after each embolization demonstrated diffuse PV
      branch occlusion in all cases. At weekly follow-up, reconstitution of flow was
      demonstrated in these branches; permanent occlusion of PV branches was not
      achieved. The mean PV pressure elevated acutely from 17.3 mm Hg +/- 0.9 to 24.5
      mm Hg +/- 4.2 (P < .01) after each embolization. However, the pressure always
      returned to baseline on the follow-up studies 1 week later. Liver function tests
      were normal. Histopathologic evaluation of the liver showed, in multiple PV
      branches, central plugs of PVA with peripheral recanalization. The liver
      parenchyma was otherwise normal. CONCLUSION: Massive embolizations of PV with PVA
      at weekly intervals failed to create permanent portal hypertension or induce
      hepatic fibrosis.

PMID- 9025052
TI  - Hepatic infarction: unusual complication of a transjugular intrahepatic
      portosystemic shunt.

PMID- 9025053
TI  - General principles for evaluation of new interventional technologies and devices.
      Technology Assessment Committee.

PMID- 9025055
TI  - Repositioning of a malaligned aortic stent-graft.

PMID- 9025054
TI  - Reporting standards for clinical evaluation of new peripheral arterial
      revascularization devices. Technology Assessment Committee.

PMID- 9025056
TI  - Successful treatment of a bleeding renal tumor with ethanol.

PMID- 9025057
TI  - Expression of S9 and actin CyIIa mRNAs reveals dorso-ventral polarity and
      mesodermal sublineages in the vegetal plate of the sea urchin embryo.
AB  - We have used whole amount in situ hybridization to analyze the patterns of
      expression of two genes, S9 and actin CyIIa, during the development of the sea
      urchin, Strongylocentrotus purpuratus. We demonstrate that at the late blastula
      stage, these two mRNAs are expressed specifically by cells of the vegetal plate.
      Their domains of expression, however, are different. S9 mRNA is broadly
      distributed within most of the vegetal plate except for the central region, while
      CyIIa expression is restricted to a population of 10-15 cells in the ventral
      region of the plate. S9-expressing secondary mesenchyme cells (SMCs) migrate from
      the vegetal plate into the blastocoel early in gastrulation and later populate
      the dorsal ectoderm. The numbers, morphology, and migratory behavior of these
      cells strongly suggest that they are pigment cells. Throughout gastrulation,
      CyIIa mRNA is expressed by a population of presumptive SMCs at the ventral aspect
      of the archenteron tip. The pattern of expression of this mRNA is dynamic,
      however, and by the early pluteus stage, CyIIa mRNA accumulates in primary
      mesenchyme cells (PMCs), SMCs, and endodermal cells of the gut. When embryos are
      treated with NiCl2, a compound that has been shown to ventralize other embryonic
      tissues, CyIIa mRNA is expressed by an increased number of cells in the vegetal
      plate in a radially symmetrical pattern. The spatial pattern of CyIIa expression
      provides the first direct molecular evidence that the vegetal plate is polarized
      along the dorso-ventral (D-V) axis of the embryo. This gene product should be a
      valuable marker in future studies of D-V axis specification, as it can be
      detected at earlier developmental stages than existing molecular markers of this
      axis. Our observations show that the vegetal plate consists of subterritories of
      gene expression, and provide further support for the view that diversification of
      the presumptive, non-skeletogenic mesoderm begins prior to the onset of
      invagination.

PMID- 9025058
TI  - Induction of oligodendrocyte progenitors in the trunk neural tube by ventralizing
      signals: effects of notochord and floor plate grafts, and of sonic hedgehog.
AB  - Recent evidence indicates that oligodendrocytes originate initially from the
      ventral neural tube. We have documented in chick embryos the effect of early
      ventralization of the dorsal neural tube on oligodendrocyte differentiation.
      Notochord or floor plate grafted at stage 10 in dorsal position induced the
      development of oligodendrocyte precursors in the dorsal spinal cord. In vitro,
      oligodendrocytes differentiated from medial but not intermediate neural plate
      explants, suggesting that the ventral restriction of oligodendrogenesis is
      established early. Furthermore, quail fibroblasts overexpressing the ventralizing
      signal Sonic Hedgehog induced oligodendrocyte differentiation in both the
      intermediate neural plate and the E4 dorsal spinal cord. These results strongly
      suggest that the emergence of the oligodendrocyte lineage is related to the
      establishment of the dorso-ventral polarity of the neural tube.

PMID- 9025059
TI  - Pluripotency and differentiation of embryonic stem cell lines from the medakafish
      (Oryzias latipes).
AB  - Small aquarium fish, like the medaka and zebrafish, offer an excellent
      opportunity to combine embryological, genetic and molecular analyses of
      vertebrate development. Pluripotent embryonic stem (ES) cells have enormous
      potential to study the totipotency and differentiation of cells and provide s
      bridge linking in vitro manipulations of the genome. In this report we describe
      the establishment, pluripotency and differentiation of medaka ES-like cell lines
      (MES). The MES cells exhibit stable growth over 18 months of culture with 100
      passages using defined culture conditions in the absence of feeder layer cells.
      They have a normal karyotype and form colonies of densely packed, alkaline
      phosphatase-positive cells resembling undifferentiated mouse ES cells. In
      suspension culture they form embryoid bodies, and under appropriate conditions,
      differentiate into a variety of cell types.

PMID- 9025060
TI  - xGCNF, a nuclear orphan receptor is expressed during neurulation in Xenopus
      laevis.
AB  - Nuclear orphan receptors are DNA binding proteins that share the domain structure
      of the nuclear hormone receptor superfamily, although ligands are unknown. We
      have identified an orphan receptor in Xenopus laevis and named it xGCNF based on
      its high degree of sequence homology to the previously described murine germ cell
      nuclear factor (mGCNF). In gel-electrophoresis mobility shift analysis
      experiments in vitro translated xGCNF and mGCNF proteins both bind specifically
      as homodimers to the same response element, a direct repeat of the half-site
      consensus AGGTCA with zero spacing (DRO). Transcripts of xGCNF are found in
      oocytes and in much smaller amounts in the testes. In developmental Northern
      blots and RNase protection using RNA from different embryonic stages, zygotic
      expression of xGCNF peaks at midneurula. From late gastrula to midneurula stages,
      an anterior to posterior concentration gradient of the RNA was observed in whole
      mount in situ analysis. This antero-posterior gradient of expression was also
      observed in exogastrulae, both in the ectoderm and mesoderm. In the midneurula
      embryo, the mRNA was predominantly found in the neural plate and neural crest.
      Transcription of xGCNF in animal cap explants occurred independent of mesoderm
      induction.

PMID- 9025061
TI  - Hroth an orthodenticle-related homeobox gene of the ascidian, Halocynthia
      roretzi: its expression and putative roles in the axis formation during
      embryogenesis.
AB  - To obtain insight into the axis-forming mechanism in ascidian embryogenesis,
      Hroth, an ascidian counterpart of orthodenticle/otx, was isolated from
      Halocynthia roretzi and its expression in embryogenesis was examined by whole
      mount in situ hybridization. It was revealed that Hroth is expressed in both
      involuting mesoendoderm and anterior ectoderm during gastrulation while later
      expression is restricted to the sensory vesicle and anterior epidermis.
      Expression pattern of Hroth around gastrulation was compared with that of Hrlim,
      the ascidian LIM class homeobox gene that is known to be expressed during
      gastrulation. In the light of the present findings on the expression of Hroth,
      properties of the axis-forming mechanism in ascidian embryogenesis are discussed.

PMID- 9025062
TI  - Spatial and temporal effects of axial structures on myogenesis of developing
      somites.
AB  - To elucidate the precise roles of axial structures in the myogenic
      differentiation of the somite, we have examined the effects of the axial organs'
      precise spatial position during migration and differentiation of somitic cells by
      using in vivo transplantation of the neural tube and of the notochord directly
      into the paraxial mesoderm. Differentiation of myotomal cells was identified
      through the use of Quox 1 antibody which recognizes specifically a quail
      homeoprotein Quox 1. We have demonstrated that both ectopic neural tube and
      notochord are able to influence the myogenesis in somites, but that the spatial
      position of axial organs and the degree of somite maturation at grafting time are
      decisive. At the level of the somites which were already formed and
      developmentally advanced (somites III-VI), both neural tube and notochord promote
      myogenesis, and the promoting effect of notochord is more efficient than that of
      the neural tube. In the newly formed somites (I-II) and/or the segmental plate
      mesoderm, the notochord inhibits the myogenesis of somites, whereas the neural
      tube plays an evident myogenic promoting role. But the myogenic effect of the
      neural tube depends not only upon the stage of developing somites and presomitic
      mesoderm, but also on the developmental maturation of the neural tube. We have
      demonstrated that the myogenic effect of the rostral part of neural tube is
      stronger than that of its caudal part. This observation suggests that there is a
      gradient of myogenic effect along the rostrocaudal axis of the neural tube, which
      depends on the developmental maturation of neural tube, and that the generation
      of skeletal muscle during somitogenesis may be in relation with the rostrocaudal
      gradient of the capacity of the neural tube to stimulate myogenesis since somites
      are also distributed along an anteroposterior axis.

PMID- 9025063
TI  - A Drosophila dystrophin-related protein, MSP-300, is required for embryonic
      muscle morphogenesis.
AB  - Proteins from the spectrin superfamily contribute to cell polarity and shape
      during the morphogenetic that accompany embryogenesis. Drosophila MSP-300, a
      member of the spectrin superfamily, is expressed in somatic, visceral and heart
      embryonic muscles. Cloning and sequence analysis of various spliced forms of MSP
      300 reveals functional and structural similarities between MSP-300 and vertebrate
      Dystrophin, the product of the Duchenne Muscular Dystrophy gene. The
      identification of a strain mutant for the MSP-300 gene is described. Analysis of
      the somatic muscle phenotype in MSP-300 mutant embryos suggests that the protein
      contributes to the integrity of the somatic and visceral muscle during periods of
      significant morphogenetic change. Functional synergism between MSP-300 and
      laminin is demonstrated by the analysis of the phenotype of embryos mutant for
      both genes. The enhancement of aberrant muscle phenotype in the double mutants
      suggests a link between MSP-300 and laminin function in mediating proper
      extension of the myotube towards the epidermal muscle attachment site. In
      addition, both genes function to establish gut integrity. In view of the
      functional and structural similarities between MSP-300 and Dystrophin, it is
      postulated that Dystrophin is not only required for proper muscle function in
      adult life but also contributes to muscle morphogenesis during the development of
      the vertebrate embryo.

PMID- 9025064
TI  - Kruppel, a Drosophila segmentation gene, participates in the specification of
      neurons and glial cells.
AB  - We report that the Drosophila segmentation gene Kruppel (Kr) is expressed in
      neural precursor cells, neurons and glial cells at different stages of
      neurogenesis and that Kr mutants develop aberrant peripheral (PNS) and central
      (CNS) nervous systems. Expression derived from a Kr minigene rescues the
      segmentation defects but these embryos continue to lack most of the neural Kr
      activity. Phenotypic analysis of the rescued embryos indicates that, in addition
      to overall effects on the PNS and CNS structure via its segmentation role, Kr
      expression in the nervous system is functionally required for establishing
      particular neural and glial fates.

PMID- 9025065
TI  - A gradient of cytoplasmic Cactus degradation establishes the nuclear localization
      gradient of the dorsal morphogen in Drosophila.
AB  - Dorsoventral axis formation in the Drosophila embryo is established by a signal
      transduction pathway that comprises the products of at least 12 maternal genes.
      Two of these genes, dorsal and cactus, show homology to the mammalian
      transcription factor NF-kappa B and its inhibitor I kappa B, respectively. As in
      the case for I kappa B and NF-kappa B, Cactus inhibits Dorsal by retaining it in
      the cytoplasm. In response to the signal produced and transmitted by the products
      of the other genes, Dorsal translocates to the nucleus preferentially on the
      ventral side of the embryo. Here, we show that Cactus forms a cytoplasmic
      concentration gradient inversely correlated to the nuclear translocation gradient
      of Dorsal. Deletions of the N-terminus and C-terminus of Cactus reveal that two
      modes of degradation control cactus activity: signal-induced degradation and
      signal-independent degradation, respectively. Genetic evidence indicates that
      degradation of Cactus is required, but not sufficient to translocates Dorsal
      completely into the nucleus.

PMID- 9025066
TI  - The ectodermal control in chick limb development: Wnt-7a, Shh, Bmp-2 and Bmp-4
      expression and the effect of FGF-4 on gene expression.
AB  - We have manipulated the chick limb bud by dorsoventrally inverting the ectoderm,
      by grafting the AER to the dorsal or ventral ectoderm and by insertion of an FGF
      4 soaked heparin bead into the mesoderm. After dorso-ventral reversal of the
      ectoderm, Wnt-7a expression is autonomous from an early stage of limb development
      in the original dorsal ectoderm. Exogenous FGF-4 causes ectopic Wnt-7a expression
      and induces ectopic Shh. In addition, exogenous FGF-4 increases the thickness of
      cartilages and also shortens them, and both Bmp-2 and Bmp-4 may mediate this
      effect. The ectoderm outside the AER can regulate not only the dorso-ventral
      polarity of the underlying mesenchyme cells but also the cartilage formation, and
      both Bmp-2 and Bmp-4 may mediate this control.

PMID- 9025067
TI  - A Krox binding site regulates protease nexin-1 promoter activity in embryonic
      heart, cartilage and parts of the nervous system.
AB  - The rat protease nexin-1 (PN-1) promoter contains a GCGGGGGCG binding site for
      the transcription factors Krox-24, Krox-20 and NGFI-C. Mutations of this site
      abolished binding of Krox-24 in vitro. The wildtype protease nexin-1 promoter
      expressed beta-galactosidase similarity to the expression of protease nexin-1
      mRNA. When the function of this Krox site was tested in vivo using transgenic F0
      embryos, mutation had two opposite effects. beta-Galactosidase expression
      increased in cartilage and heart at both stages E11.5 and E13.5, but was
      abolished in nerves of the central and peripheral nervous system at stage E13.5.
      These results suggest that Krox factors are among the important transcription
      factors regulating protease nexin-1 expression and thereby intracellular
      proteolytic activity in embryonic heart, cartilage and parts of the nervous
      system.

PMID- 9025068
TI  - Distal cis-acting elements restrict expression of the CyIIIb actin gene in the
      aboral ectoderm of the sea urchin embryo.
AB  - The distal region of the S. purpuratus actin CyIIIb gene, between -400 and -1400
      nucleotides, contains at least three distinct cis-acting elements (C1R, C1L and
      E1) which are necessary for correct expression of fusion reporter genes in
      transgenic sea urchin embryos. The contribution of these elements in the temporal
      and spatial regulation of the gene was analyzed by single and double site
      directed mutagenesis in fusion constructs which carry the bacterial
      chloramphenicol acetyl transferase (CAT) gene as a reporter. Following
      microinjection of the transgenes in sea urchin embryos, the activity of the
      mutants was compared to the wild type in time and space by measuring CAT activity
      at the blastula and pluteus embryonic stages and by in situ hybridization to the
      CAT mRNA at pluteus stage. Our results indicate that E1 is involved in the
      temporal regulation of CyIIIb and that all three elements are necessary and
      sufficient to confer aboral (dorsal) ectoderm specificity to the proximal
      promoter. This is achieved by suppressing the promoter's activity in all other
      tissues by the cooperative interaction of the cis-acting elements. The C1R
      element, binding site of the nuclear receptors SpCOUP-TF and SpSHR2, is by itself
      sufficient to restrict expression in the ectoderm, whereas the aboral ectoderm
      restricted expression requires in addition the presence of both C1L and E1. It is
      therefore evident, that the actin CyIIIb gene is exclusively expressed in the
      aboral ectoderm by a combinatorial repression in all other cell lineages of the
      developing embryo.

PMID- 9025070
TI  - Pancreatic-duodenal homeobox 1 -role in gastric endocrine patterning.
AB  - The gastrointestinal tract is subdivided into regions with different roles in
      digestion and absorption. How this patterning is established is unknown. We now
      report that the pancreatic-duodenal homeobox 1 gene (pdx1) is also expressed in
      cells of the distal stomach. Positive cells include subpopulations of the three
      main endocrine (gastrin, somatostatin and serotonin) cell types of this region.
      Pdx1 deficient mice were virtually devoid of gastrin cells, had normal numbers of
      somatostatin cells and increased numbers of serotonin cells. Pdx1 is thus
      important for development of the gastrin cells of the antropyloric mucosa of the
      stomach and probably acts by controlling the fate of gastrin/serotonin precursor
      cells.

PMID- 9025069
TI  - Spatial expression of a forkhead homologue in the sea urchin embryo.
AB  - Echinoderms are the sister group of the chordates and hemichordates within the
      deuterostomes. They lack a notochord or any structures obviously homologous with
      it. To gain insight into developmental mechanisms important in the origin and
      early evolution of chordates, we investigated sea urchin homologues of chordate
      genes that are implicated in notochord formation, viz. Brachyury and HNF-3 beta.
      Here we report the pattern of expression of a sea urchin orthologue of forkhead,
      Hphnf3 which is present as a single copy per haploid genome. An Hphnf3 transcript
      of 3.0 kb was first detected at the swimming blastula stage, accumulated
      maximally at the gastrula and prism-embryo stages, and decreased at the pluteus
      larva stage. In situ hybridization signals were found in cells of the vegetal
      plate of the swimming blastula. During gastrulation, intense staining was evident
      in the cells surrounding the blastopore, whereas weak staining was detected in
      the invaginating archenteron. At the prism-embryo stage, the entire archenteron
      stained intensely; then, at pluteus stage, the larva staining decreased in
      intensity. The forkhead and Brachyury genes begin to be expressed almost
      simultaneously in sea urchin embryos, in the vegetal plate at the late blastula
      stage. After the onset of gastrulation, however, Hphnf3 is expressed in the
      posterior part of the archenteron, whereas the Brachyury orthologue, HpTa, is
      expressed in the secondary mesenchyme founder cells, which occupy the anterior
      tip of archenteron. Hphnf3 may contribute to specification of embryonic cells as
      archenteron, and the role of HpTa may be directed towards specification of
      mesodermal founder cells. Except for the basal character of expression in
      endoderm and endomesoderm, these transcription factors are clearly utilized
      differently in chordates.

PMID- 9025071
TI  - Very early and transient vegetal-plate expression of SpKrox1, a Kruppel/Krox gene
      from Stronglyocentrotus purpuratus.
AB  - All endodermal and mesenchymal cells of the sea urchin embryo descend from the
      vegetal plate, a thickened epithelium of approximately 50 cells arising at the
      early blastula stage. Cell types that derive from the vegetal plate are specified
      conditionally by inductive interactions with underlying micromeres, but the
      molecular details of vegetal-plate specification remain unresolved. In a search
      for regulatory proteins that have roles in vegetal-plate specification, a screen
      was performed to clone Kruppel/Krox-related genes from a Strongylocentrotus
      purpuratus embryo cDNA library. One newly identified clone, named SpKrox1,
      contained four zinc fingers and a leucine zipper domain. SpKrox1 expression was
      low in unfertilized eggs, increased severalfold to the early blastula stage and
      decreased between the early gastrula and pluteus stages. SpKrox1 mRNA was first
      seen in macromeres of 16-cell stage embryos and was restricted to cells of the
      developing vegetal plate thereafter. Vegetal-plate expression corresponded to a
      ring of cells around the blastopore and overlapped the expression patterns of
      other genes with potential roles in vegetal plate-specification. As the vegetal
      plate cells invaginated into the blastopore, SpKrox1 expression was lost,
      suggesting that its role was not in endoderm differentiation per se but rather in
      the initial establishment of the vegetal plate.

PMID- 9025072
TI  - The serpent gene is necessary for progression through the early stages of fat
      body development.
AB  - The serpent (srp) gene, also known as ABF, codes for a GATA-like transcription
      factor and is involved in the transcription activation of Adh in the larval fat
      body or adipose tissue. Here, we describe the tissue-specific distribution of SRP
      protein in various stages of embryonic development and describe srp's role in
      early fat-cell development. SRP protein was detected in the progenitor fat-body
      cells and is present in the developing fat-body cells and in the mature embryonic
      fat body. An analysis of srp embryos revealed a gradual loss of precursor fat
      cells that is likely due to apoptosis. Within the fat-cell lineage, srp is
      necessary for progression through early stages of fat-cell development and may be
      involved in the transactivation of genes necessary for fat-cell differentiation.

PMID- 9025073
TI  - Involvement of Livertine, a hepatocyte growth factor family member, in neural
      morphogenesis.
AB  - The formulation of the nervous system in vertebrate embryos involves extensive
      morphogenetic movements that include the folding of the neural tube and the
      migration of neural crest cells. Changes in cell shape and cell movements
      underlie neural morphogenesis but the molecular mechanisms involved in these
      processes in vivo are not well understood. Here, we show that a new member of the
      hepatocyte growth factor family, which we name Livertine, is expressed in frog
      embryos in neural cells including neural crest and midline neural plate cells
      which are undergoing pronounced morphogenetic movements. The ectopic expression
      of Livertine perturbs gastrulation and leads to positional changes in injected
      cells without apparently changing cell type. These results suggest that one of
      the normal functions of Livertine is the control of neural morphogenesis in the
      vertebrate embryo.

PMID- 9025074
TI  - Combinatorial signalling by Xwnt-11 and Xnr3 in the organizer epithelium.
AB  - The epithelium of the Spemann organizer plays an important role in embryonic axis
      formation and transplantation experiments have shown that epithelial organizer
      cells have potent axis-inducing potential. Known axis-inducing molecules like
      noggin and chordin are not expressed in the epithelium and cannot account for its
      inductive properties. Xwnt-11 is expressed in the epithelium but has only poor
      dorsalizing activity. In an expression screen for genes that are able to
      functionally cooperate with Xwnt-11 we have identified a cDNA encoding Xenopus
      nodal-related 3 (XNR3), a member of the TGF-beta family, coexpressed with Xwnt-11
      in the organizer epithelium. Xwnt-11 and Xnr3 act highly cooperatively in
      inducing secondary embryonic axes and dorsalizing ventral mesoderm. Xwnt-11/Xnr3
      interfere with BMP signalling without themselves inducing chordin or noggin. The
      results indicate that induction by the organizer epithelium may result from the
      combinatorial action of instructive Xnr3 and permissive Xwnt-11 signalling.

PMID- 9025076
TI  - Polymerase chain reaction for the detection of Pseudomonas aeruginosa,
      Stenotrophomonas maltophilia and Burkholderia cepacia in sputum of patients with
      cystic fibrosis.
AB  - Occurrence of Pseudomonas aeruginosa, Stenotrophomonas (Xanthomonas) maltophilia
      and Burkholderia (Pseudomonas) cepacia in sputum of cystic fibrosis (CF) patients
      was demonstrated with a simple and rapid polymerase chain reaction (PCR)
      technique. The PCR was performed with a set of three primer pairs based on 16S
      rRNA sequences after sputum preparation with dithiothreitol and NaOH lysis. All
      three pathogens could be individually detected by the use of this technique. To
      prevent carry-over contamination, dUTP and uracil-N-glycosylase were included in
      the reaction. The amplicons were visualized by agarose gel electrophoresis.
      Sputum culture was performed on all samples. Ninety specimens from CF patients
      were analysed. The sensitivity for the detection of P. aeruginosa was 37/40 (93%)
      compared to culture. Bacterial growth of P. aeruginosa was found in three cases,
      where PCR amplicons were not detected, while PCR was positive in five cases,
      where culture did not reveal the presence of this bacterium. For this reason, the
      specificity was 45/50 (90%). For S. maltophilia, the PCR was less sensitive than
      culture (positive in three of six cases). In our series, B. cepacia was detected
      by culture in one case and this was also detected by PCR. There were no false
      positive PCR results regarding S. maltophilia or B. cepacia. Thus, combined PCR
      based detection of these three clinically relevant bacteria in sputum samples
      from CF patients can be performed by a reliable technique in a relatively simple
      manner. The present data indicate a high sensitivity and specificity for P.
      aeruginosa. The lower sensitivity observed for the detection of S. maltophilia in
      sputum and B. cepacia, as estimated from laboratory strains, may depend on PCR
      conditions and genetic heterogeneity, respectively. The greatest gains with this
      method can be made when it is used for the early detection of P. aeruginosa in
      sputum-producing CF patients.

PMID- 9025075
TI  - Ectopic lens induction in fish in response to the murine homeobox gene Six3.
AB  - Recent findings show an unexpected conservation of genes involved in vertebrate
      and insect eye development. The Drosophila homeobox gene sine oculis is crucial
      for eye development. Its murine homologue, Six3 is expressed in the anterior
      neural plate, a region which is involved in lens induction in Xenopus. To examine
      whether Six3 participates in the process of eye formation, mouse Six3 was
      ectopically expressed in fish embryos. The results show that Six3 is sufficient
      to promote ectopic lens formation in the area of the otic vesicle and that
      retinal tissue is not a prerequisite for ectopic lens differentiation. Our
      findings suggest a conserved function for Six3 in metazoan eye development.

PMID- 9025077
TI  - Differentiation of seventeen genospecies of Acinetobacter by multiplex polymerase
      chain reaction and restriction fragment length polymorphism analysis.
AB  - The 17 described genomic species (DNA groups) of the genus Acinetobacter,
      including the type strains of the seven named species, were studied by using a
      multiplex PCR. The multiplex PCR assay combined two primer sets (rA1 and rA2 for
      recA gene target; rib1 and rib2 for 16S rDNA sequence) in a single reaction.
      Restriction analysis with two enzymes (Mbol and Hinfl) of the enzymatically
      amplified products allowed identification of all genospecies. This technique
      proved to be a rapid and reliable method for the identification of the
      Acinetobacter genomic species including the closely related DNA groups (1, 2, 3,
      13). The results of this study suggest that the proposed method can be used for
      the identification of Acinetobacter spp. and as such may help to elucidate the
      ecology and clinical significance of the different species of this genus.

PMID- 9025078
TI  - A PCR-DNA probe assay specific for Bacteroides forsythus.
AB  - Bacteroides forsythus is a fastidious anaerobic Gram-negative organism associated
      with active periodontal disease. The ability of random amplified polymorphic DNA
      (RAPD) fingerprinting to generate species-specific markers was exploited towards
      the construction of a polymerase chain reaction (PCR)-DNA probe assay specific
      for B. forsythus. The strategy included the four following steps: (1)
      construction of a first generation DNA probe based on a 507-bp RAPD species
      specific marker; (2) cloning and sequencing the 507-bp RAPD marker; (3) design of
      the primer pair Bf 392-1/Bf 392-2 flanking a 392-bp specific internal sequence;
      and (4) synthesis of quantities of a 392-bp second generation DNA probe by PCR
      amplification. The PCR-DNA probe assay includes a PCR amplification of a 392-bp
      specific sequence in the genomic DNA of B. forsythus strains followed by
      hybridization with the 392-bp digoxigenin-labelled second generation probe. We
      observed strong, specific hybridization with the amplified DNAs from 11 stains of
      B. forsythus and no cross-hybridization with the PCR products from 22 foreign
      species. The PCR-DNA probe assay must be seen as a highly specific and sensitive
      method for the detection of B. forsythus in mixed infections.

PMID- 9025080
TI  - Competitive reverse transcription/polymerase chain reaction for the
      quantification of p53 and mdm2 mRNA expression.
AB  - Wild-type p53 (wtp53) is a tumour suppressor gene involved in cell cycle
      regulation. The mdm2 protein can complex with the p53 protein and influence its
      function as a regulator of cell growth. To detect and quantify wtp53 and mdm2
      mRNA expression, we established the competitive reverse transcription/polymerase
      chain reaction for these genes and for the housekeeping gene glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). The target RNA differed from the competitor cRNA
      by having 183 bp, 205 bp and 173 bp deletions for p53, mdm2 and GAPDH,
      respectively. Target RNA and known concentrations of competitor cRNA were co
      reverse transcribed and co-amplified with the same primers. Target cDNA and the
      corresponding competitor cDNA were amplified at the same efficiency.

PMID- 9025079
TI  - A simple method to design PCR primer to detect genomic DNA of parasites and its
      application to Dirofilaria immitis.
AB  - A simple method to design a polymerase chain reaction (PCR) primer for parasites
      of interest was developed using Dirofilaria immitis as a test sample. The method
      involved the cloning and sequencing of randomly amplified DNA of the parasite,
      and designing a primer based on the resulting DNA sequence. Using the primer, DNA
      fragments of the expected length were amplified by a regular PCR with genomic DNA
      of Dirofilaria immitis.

PMID- 9025081
TI  - Identification of fish species using random amplified polymorphic DNA (RAPD).
AB  - The random amplified polymorphic DNA (RAPD) method was investigated as a
      potential fish species identification method. One hundred and sixteen specimens
      from eight species of fish were analysed. The eight species tested were
      barramundi, Nile perch, john dory, mirror dory, silver dory, spikey oreo, warty
      oreo and smooth oreo. The predominant species tested was barramundi; 80 specimens
      of this species were analysed. Of these samples, 42 had been individually
      verified by independent sources. The RAPD profiles generated were consistent
      within this group. The remaining samples were retail purchased and consisted of
      24 imports and eight local whole small barramundi and six fillets. All of the
      whole barramundi, including the imported fish, generated profiles which agreed
      with the verified samples. Four of the six fillets purchased did not match the
      typical barramundi profile, three profiles, however, were consistent with those
      generated for Nile perch. Species-specific profiles were also generated for the
      other seven species analysed by RAPD. One john dory, from five fillets tested,
      did not comply with the six authenticated sample. All of the RAPD profiles were
      resolved by agarose gel electrophoresis. Forty nine RAPD profiles including those
      that did not match were also confirmed by native polyacrylamide gel
      electrophoresis (PAGE) on a DNA sequencer.

PMID- 9025082
TI  - Identification of a human endogenous LTR-like sequence using HIV-1 LTR specific
      primers.
AB  - Using 'consensus' primers derived from the LTR region of 15 HIV-1 isolates, a
      fragment of 583 bp was amplified from human DNA. Even though specificity was
      confirmed by Southern blot analysis with a conserved LTR oligonucleotide probe,
      no significant homologies were detected to either retroviral regions or human or
      non-human published sequences. Nevertheless, when used as a probe, the 583-bp
      fragment identified a unique DNA sequence in the human genome on chromosome 1,
      and cross-reactive sequences in monkey, but not mouse, DNA. This novel, unique
      and conserved sequence of 583 bp was used to isolate a human HS-1 clone in which
      the structural property of a viral LTR could be identified.

PMID- 9025084
TI  - A common polymorphism in exon 46 of the human autosomal dominant polycystic
      kidney disease 1 gene (PKD1).
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      single gene diseases in humans. We have identified a synonymous T to C transition
      polymorphism in exon 46 of the PKD1 gene (12838T-->C, Pro4209Pro). The
      polymorphism was present with similar frequencies in ADPKD patients and
      unaffected individuals. The heterozygosity, determined in 89 Italian individuals,
      was 0.347. The frequency of the rarer allele was 0.222. This polymorphism is easy
      to determine as it abolishes a naturally occurring Ddel restriction site. The
      availability of an additional intragenic marker in the PKD1 gene will improve the
      accuracy of linkage studies in ADPKD families.

PMID- 9025083
TI  - Analysis of Epstein-Barr virus (EBV) type and variant in spontaneous
      lymphoblastoid cells and Hu-SCID mouse tumours.
AB  - Epstein-Barr virus (EBV) type and strain variations were examined using both
      lymphoblastoid cell lines (LCLs), spontaneously derived in vitro from peripheral
      blood mononuclear cells (PBMC) of 15 HIV-1-seropositive individuals; and SCID
      mouse tumours induced by inoculation of PBMC from 11 healthy human donors (Hu
      SCID tumours). Polymerase chain reaction (PCR) analysis disclosed that all but
      one of the 26 EBV + samples harboured EBV nuclear antigen (EBNA) 2 and 3C type A
      virus. On the other hand, single strand conformation polymorphism (SSCP) analysis
      using Epstein-Barr encoded RNA (EBER) specific primers detected an AG876-like
      (type B) band pattern in 21 of the 26 EBV + samples. Three Hu-SCID tumours scored
      as B95.8-like (type A), and two showed neither a type A nor a type B SSCP
      migration pattern. Sequence analysis of the amplified EBER fragments confirmed
      the PCR-SSCP findings; moreover, additional mutations were present not only in
      the two EBV + samples with anomalous SSCP pattern, but also in two other samples
      with a standard SSCP profile. Thus, EBER analysis did not correlate with EBNA
      typing, and appeared to be unsuitable for EBV type assessment. Latent membrane
      protein (LMP) analysis disclosed, on the whole, sever size variants: as expected,
      the differences were due to the variable numbers of a 33-bp repeat in the
      amplified fragment, as assessed by direct sequencing. The broader variability
      detected by LMP analysis should prove more useful than typing for assessing the
      presence of single and/or mixed variants resulting from EBV reactivation and/or
      reinfection.

PMID- 9025085
TI  - Informative MspI polymorphism adjacent to exon 3 of the p16INK4 (MTS1) gene.

PMID- 9025086
TI  - Two polymorphic repeats in the candidate region for the haemochromatosis gene.

PMID- 9025087
TI  - Rapid assay for detection of methicillin-resistant Staphylococcus aureus using
      multiplex PCR.
AB  - The presence or absence of the mecA gene, the determinant of resistance to all
      beta-lactam antibiotics, was examined in clinical isolates of Staphylococcus
      aureus by multiplex polymerase chain reaction (MPCR). Two pairs of primers were
      used, which yielded two specific products; a 280-bp nuc- based PCR fragment
      (amplification product of the nuc gene encoding specific Staphylococcus aureus
      nuclease) and a 533-bp mecA-based PCR fragment (amplification product of the mecA
      gene). The MPCR system was designed to be incorporated into the work flow in
      clinical diagnostic laboratories as a routine analysis.

PMID- 9025088
TI  - A simplified semiquantitative determination of hepatitis C virus genome molecules
      by the end-point dilution method.
AB  - We describe a semiquantitative method to measure hepatitis C virus (HCV) viral
      particle numbers, by carrying out reverse-transcription polymerase chain reaction
      (RT-PCR) on serial dilutions of serum samples. The virus concentrations measured
      were 10(3)-10(6) viral particles ml-1 of serum. The method described is
      relatively quick, and the only required manipulation is dilution of the serum. An
      optimal RT-PCR method is used for diluted and undiluted samples.

PMID- 9025089
TI  - The presence of a pseudogene may affect the use of HPRT as an endogenous mRNA
      control in RT-PCR.
AB  - Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) has
      been used extensively as a tool to measure expression levels of mRNA species.
      Many commonly used endogenous mRNA control species are known to have genomic
      pseudogenes, which can confound RT-PCR results if not accounted for. The
      hypoxanthine phosphoribosyltransferase gene (HPRT) has previously been used as an
      mRNA control to circumvent these difficulties, since it was believed that no
      pseudogenes existed. The existence of a pseudogene of HPRT is reported, and
      researchers are warned that this gene cannot be used as an endogenous mRNA
      control without taking appropriate precautions.

PMID- 9025090
TI  - Quantitative and qualitative studies of micronucleus induction in mouse
      erythrocytes using flow cytometry. I. Measurement of micronucleus induction in
      peripheral blood polychromatic erythrocytes by chemicals with known and suspected
      genotoxicity.
AB  - Quantitative and qualitative aspects of the in vivo micronucleus-inducing
      potential of five chemicals were studied using flow cytometric enumeration of
      micronucleated polychromatic peripheral blood erythrocytes in mice. The chemicals
      were hydroquinone, vinblastine sulphate, chloral hydrate (tested in two different
      mouse strains), 5-bromo-2-deoxyuridine and 2-chlorobenzylidene malonitrile.
      Repeat samplings of peripheral blood were made at 0, 24, 40, 48 and 72 h and for
      low doses of 5-bromo-2-deoxyuridine 96 h after i.p. treatment. The agents
      hydroquinone (lowest effective dose 25 mg/kg), vinblastine sulphate (lowest
      effective dose 0.05 mg/kg) and 5-bromo-2-deoxyuridine (lowest effective dose 200
      mg/kg) gave rise to significant increases in the frequencies of micronucleated
      polychromatic erythrocytes. No significant induction of micronucleated
      polychromatic erythrocytes by 2-chlorobenzylidene malonitrile or chloral hydrate
      was found. The frequencies of induced micronucleated polychromatic erythrocytes
      peaked at 40 h after hydroquinone treatment, at 48 h after vinblastine treatment
      and at 72 h after 5-bromo-2-deoxyuridine treatment with evident dose-dependent
      differences in the kinetics of the induction of micronucleated polychromatic
      erythrocytes. The mean relative Hoechst 33342 fluorescence of the populations of
      induced micronucleated polychromatic erythrocytes was used as an indicator of the
      DNA content of induced micronuclei. These values were found to be in agreement
      with the presumed mechanisms of micronucleus induction for hydroquinone,
      vinblastine sulphate and 5-bromo-2-deoxyuridine. Flow cytometric enumeration of
      micronucleated polychromatic erythrocytes in peripheral blood is an efficient
      method for the study of in vivo micronucleus induction, combining rapid analysis
      and high sensitivity with information on possible mechanisms of micronucleus
      induction. The method also allows a substantial reduction in the number of
      animals needed.

PMID- 9025091
TI  - Quantitative and qualitative studies of micronucleus induction in mouse
      erythrocytes using flow cytometry. II. Analysis of micronuclei of aneugenic and
      clastogenic origin by dual-colour FISH on populations of bone marrow PCEs flow
      sorted on the basis of their relative DNA content.
AB  - Simultaneous dual-colour fluorescent in situ hybridization (FISH) with the major
      and minor mouse satellite probes was performed on flow-sorted fractions of
      micronuclei with defined Hoeschst 33342 fluorescence intensities, reflecting
      their relative DNA content. The purpose of the study was to investigate the
      relationship between probe binding and the size of micronuclei induced by a set
      of chemicals with different mechanisms of micronucleus induction. The agents
      studied were vinblastine, cyclophosphamide, hydroquinone and 5-bromo-2
      deoxyuridine. The Hoechst 33342 fluorescence distributions of induced micronuclei
      differ markedly between cyclophosphamide, vinblastine and hydroquinone. While the
      distributions for cyclophosphamide and vinblastine agree well with those obtained
      for other model aneugens and clastogens, hydroquinone shows a distribution with
      characteristics similar to both clastogens and aneugens. A comparison between the
      Hoechst 33342 fluorescence distributions of hydroquinone-induced micronuclei
      positive for both major and minor probes and those positive for the major probe
      only indicates that the former consist of whole chromosomes, while the latter
      originate from chromosome fragments. The absolute frequency and Hoechst 33342
      fluorescence distribution of major-only-positive micronuclei induced by
      vinblastine indicates that this model aneugen also shows a certain in vivo
      clastogenic potential. Micronuclei induced by 5-bromo-2-deoxyuridine indicate
      that this agent is a clastogen, preferentially inducing pericentric breaks, but
      may also to some extent be aneugenic.

PMID- 9025092
TI  - Modulating factors of individual sensitivity to diepoxybutane: chromosome
      aberrations induced in vitro in human lymphocytes.
AB  - Peripheral blood lymphocytes from a sample of 62 randomly selected donors were
      analysed for spontaneous and diepoxybutane (DEB)-induced chromosomal aberrations
      (CA). These individuals were part of a larger sample of 122 subjects whose DEB
      responsiveness was evaluated by means of sister chromatid exchange (SCE)
      analysis. Confounding factors (such as smoking, wine and coffee consumption,
      occupation and haematological factors) were analysed for their effect on
      individual DEB-responsiveness, but no statistically significant associations were
      observed. Interestingly, a bimodal distribution of aberrant cell frequencies was
      clearly detectable, showing the existence of DEB-sensitive subjects belonging to
      the second mode (CA frequencies > 19%). When responsiveness evaluated by means of
      CA induction was compared with SCE responsiveness, it was noted that all SCE
      inducible subjects (> 110.9 SCEs/cell) belonged to the second mode of CA
      frequency distribution. On the other hand, highly CA inducible individuals did
      not necessarily show a higher SCE-response, although their DEB-induced SCE
      frequencies were above average (92 SCEs/cell). DEB-induced CA frequency
      correlated with baseline levels, indicating that DEB-sensitive individuals also
      showed higher spontaneous chromosome damage (3.6 versus DEB-resistant 2%, P <
      0.05). Finally, when simple and multiple regression analyses were carried out,
      DEB-sensitivity appeared negatively related to haematic concentrations of
      proteins and uric acid (intercept 0.131 +/- 0.011, slope -0.029 +/- 0.0116, r = 
      0.39; P < 0.01), probably due to its antioxidant activity. This finding confirmed
      previous observations on the scavenger activity of plasma factors on DEB
      mutagenicity.

PMID- 9025093
TI  - Effects of nitrous acid treatment on the survival and mutagenesis of Escherichia
      coli cells lacking base excision repair (hypoxanthine-DNA glycosylase-ALK A
      protein) and/or nucleotide excision repair.
AB  - Deoxyinosine occurs in DNA by spontaneous deamination of adenine or by
      incorporation of dITP during replication. Hypoxanthine residues (HX) are
      mutagenic and give rise to A-T-->G-C transition. They are substrates for the
      Escherichia coli product of the alkA gene, the 3-methyl-adenine-DNA glycosylase
      II (ALK A protein). In mammalian cells and in yeast, HX is excised by the
      counterpart of ALK A protein, the ANPG or the MAG proteins respectively. We have
      investigated in vivo the contribution of the alkA gene to counteract the lethal
      and/or mutagenic effects of HX residues induced by nitrous acid treatment. Using
      an E.coli strain allowing the detection of A-T-->G-C transition, we show that the
      alkA mutant has a slightly increased spontaneous rate of mutation and about the
      same sensitivity when treated with HNO2 as compared with the wild-type strain.
      Using the E.coli alkA mutant carrying a multicopy plasmid expressing the ALK A
      protein or the ANPG protein, we barely observe any effect of HNO2 treatment on
      sensitivity and mutation rate of the bacteria. In contrast, the same experiment
      performed with a uvrA- strain, deficient in nucleotide excision repair (NER),
      shows that this mutant is extremely sensitive to HNO2 treatment. Furthermore, the
      sensitivity and the spontaneous mutation rate observed in the double mutant alkA-
      uvrA- are almost identical to those of the uvrA- mutant. Hence, NER has the major
      role in vivo for the repair of lethal and mutagenic lesions induced by HNO2.

PMID- 9025094
TI  - Topoisomerase II inhibitors fail to induce chromosome-type aberrations in
      etoposide-resistant cells: evidence for essential contribution of the cleavable
      complex formation to the induction of chromosome-type aberrations.
AB  - The induction of chromosome-type aberrations is mediated by stabilization of the
      DNA-topoisomerase II (topo-II) complex, the cleavable complex (CC), induced by
      topo-II inhibitors. In the present study, in order to confirm the critical
      contribution of topo-II in producing chromosome-type aberrations, the
      inducibility of chromosome-type aberrations by topo-II inhibitors was compared
      between human epidermoid cancer KB cells and their mutant cells (KB/ VP-2 cells)
      which were resistant to etoposide (VP-16) and which have reduced levels of topo
      II and its gene expression. KB/VP-2 cells were resistant to the cytotoxicity of
      topo-II inhibitors and most resistant to etoposide. In KB cells treated with
      etoposide which had accumulated CC, chromosome-type aberrations but not chromatid
      type aberrations were efficiently induced, as has already been reported in
      Chinese hamster fibroblasts. In contrast, in KB/VP-2 cells with no accumulation
      of CC, etoposide induced mainly chromatid-type aberrations, with a few chromosome
      type aberrations. Unlike etoposide, however, adriamycin, which was known to
      accumulate CC in Chinese hamster fibroblastic cells, neither induced chromosome
      type aberrations nor accumulated CC in either KB or KB/VP-2 cells. No difference
      in cell incorporation of [3H]etoposide between the two cell lines was observed.
      These findings indicate that CC formation contributes to the induction of
      chromosome-type aberrations, although the reason why adriamycin could not
      accumulate CC in KB cells is not clear. This may suggest a mechanism for
      resistance to topo-II inhibitors in cancer chemotherapy.

PMID- 9025095
TI  - Testing of p-dichlorobenzene and hexachlorobenzene for their ability to induce
      DNA damage and micronucleus formation in primary cultures of rat and human
      hepatocytes.
AB  - The genotoxicity of p-dichlorobenzene (DCB) and hexachlorobenzene (HCB) was
      evaluated in primary cultures of rat and human hepatocytes. DNA fragmentation was
      measured by the alkaline elution technique and clastogenic activity by the
      increase in micronucleus formation. In rat hepatocytes, exposure to
      concentrations of DCB ranging from 0.56 to 3.2 mM and of HCB from 0.1 to 0.56 mM
      did not induce any significant increase in the frequency of DNA breaks but
      consistently produced a statistically significant increase in the frequency of
      micronucleated cells. In human hepatocytes, under the same experimental
      conditions, the response to DCB was negative in terms of both DNA fragmentation
      and clastogenic effect, whereas HCB produced a significant increase in the
      frequency of both DNA breaks and micronuclei. Taken as a whole these results
      suggest that of the two pesticides examined only HCB should be considered as a
      weak genotoxic carcinogen.

PMID- 9025096
TI  - A low content of ERCC1 and a 120 kDa protein is a frequent feature of group F
      xeroderma pigmentosum fibroblast cells.
AB  - The ERCC1 protein has been predicted to form part of a tight complex with a
      protein partner, the yet-unidentified XPF/ERCC4 protein, in normal human cells.
      We used an anti-ERCC1 antibody to detect the complex by immunoprecipitation and
      immunoblotting. The amount of ERCC1 protein expressed in five different XP-F cell
      strains was 1/ 5-1/34 of that of the protein in normal and XP cell strains
      representing other complementation groups. A 120 kDa protein was co
      immunoprecipitated with ERCC1 by the anti-ERCC1 antibody, and the amount of the
      120 kDa protein in XP-F cell strains was 1/5-1/8 of that of the protein in normal
      and XP cell strains representing other complementation groups. The XPA protein
      was not co-immunoprecipitated with ERCC1 in any cell strain. These results
      demonstrate that a low level of ERCC1 and the 120 kDa protein is a frequent
      feature of XP-F cell extracts and that a lower amount of a complex between these
      proteins occurs in XP-F cells than in normal cells.

PMID- 9025098
TI  - Dopamine receptors and brain function.
AB  - In the central nervous system (CNS), dopamine is involved in the control of
      locomotion, cognition, affect and neuroendocrine secretion. These actions of
      dopamine are mediated by five different receptor subtypes, which are members of
      the large G-protein coupled receptor superfamily. The dopamine receptor subtypes
      are divided into two major subclasses: the D1-like and D2-like receptors, which
      typically couple to Gs and Gj mediated transduction systems. In the CNS, the
      various receptor subtypes display specific anatomical distributions, with D1-like
      receptors being mainly post-synaptic and D2-like receptors being both pre- and
      post-synaptic. D1 and D2 dopamine receptors, the most abundant subtypes in the
      CNS, appear to be expressed largely in distinct neurons. Substance P and
      dynorphin, which are expressed in D1 receptor-containing neurons, as well as pre
      proenkephalin in D2 receptor-containing neurons, have been used as monitors of
      dopaminergic activity in the CNS. Expression of immediate early genes, in
      particular fos, has also been found to correlate with dopaminergic transmission.
      Dopamine released from the hypothalamus controls the synthesis and secretion of
      prolactin from the anterior pituitary via D2 dopamine receptors. As yet none of
      the dopamine receptor subtypes have been associated with the etiology of
      psychotic disorders, such as schizophrenia. However, the recent characterization
      of D3 and D4 receptors which are, interestingly, expressed in areas of the CNS
      mediating cognition and affect or showing increased affinity for certain
      neuroleptics, have renewed the interest and hope of finding effective
      neuroleptics devoid of side effects. Finally, the recent production of
      genetically-derived animals lacking several of these receptor genes should help
      elucidate which specific physiological paradigms the receptors mediate.

PMID- 9025097
TI  - Mutagenicity of the potent rat hepatocarcinogen 6BT to the liver of transgenic
      (lacI) rats: consideration of a reduced mutation assay protocol.
AB  - 6-(p-dimethylaminophenylazo)benzothiazole (6BT) is an unusually potent rat
      hepatocarcinogen, producing large malignant liver tumours after only 2-3 months
      of dietary administration in a riboflavin-deficient diet. This azocarcinogen has
      been evaluated in a Big Blue F344 transgenic rat (lacI) gene mutation assay. In a
      reproduction of the early stages of the carcinogenesis bioassay of this agent,
      rats were maintained on a riboflavin-deficient diet and were given 10 consecutive
      daily doses of 6BT (10 mg/kg) by oral gavage. The animals were killed and the
      livers examined 11 days after the final dose. The livers of 6BT-treated rats
      showed evidence of hepatocellular hypertrophy in centrolobular areas, with some
      indication of an increased incidence of mitotic figures. An approximately 10-fold
      increase in the mutation frequency of DNA isolated from an aliquot of the
      combined liver homogenates of 6BT-treated rats was observed over that obtained
      from an equivalent aliquot from control animals. Examination of DNA samples
      isolated from the livers of individual animals confirmed that 6BT was mutagenic
      in Big Blue rat livers. These data extend the sensitivity of this transgenic
      assay to include azo hepatocarcinogens. The determination of mutation frequencies
      using pooled tissue samples represented a major resource-saving adaptation of the
      assay protocol in the present study; the general advantages and disadvantages of
      this practice are discussed.

PMID- 9025099
TI  - Modulation of dopamine release in the nucleus accumbens by 5-HT1B agonists:
      involvement of the hippocampo-accumbens pathway.
AB  - Changes in extracellular levels of dopamine (DA), DA metabolites DOPAC and HVA,
      and the serotonin metabolite 5-HIAA, were measured by microdialysis in the rat
      nucleus accumbens (n. acc) after treatments with serotonin (5-HT)1A (8-OH-DPAT)
      or 5-HT1B (RU 24969 and S-CM-GTNH2) receptor agonists. Subcutaneous injections of
      RU 24969 (0.02-2 mg/kg) dose-dependently decreased 5-HIAA levels (0 to -38%), and
      also induced long-lasting increases in DA levels (0 to +37%) and DOPAC (+11% at
      the dose 0.5 mg/kg) in the shell of the n. acc, whereas 8-OH-DPAT (0.25 and 0.5
      mg/kg) reduced 5-HIAA levels (-25%) and very slightly increased DOPAC at the
      lower dose (+4%), but had no effect on DA levels. Three weeks after interruption
      of the subicular efferent projections, the increase in DA levels previously
      observed after systemic injections of RU 24969 was abolished. Microinjections of
      RU 24969 (10 micrograms/microliter) or S-CM-GTNH2 (3 micrograms/microliter) into
      the ventral subicular area reproduced the effects of systemic injections of RU
      24969 cn DA levels and increased DOPAC (+13%; +19%, respectively) and HVA levels
      (+23%; +24%), with no significant change in 5-HIAA. It is concluded that: (1)
      serotonin interacts with the mesolimbic dopaminergic system through 5-HT1B, but
      not 5-HT1A, receptors: and (2) serotonin interaction with the mesolimbic
      dopaminergic system involves postjunctional 5-HT1B heteroreceptors located in the
      ventral subicular area, which modulate the activity of glutamatergic hippocampo
      accumbens pathways and only secondarily alter DA levels in the n. acc. The
      possible relevance of these results for schizophrenia is discussed.

PMID- 9025100
TI  - Tetrodotoxin-sensitivity of nicotine-evoked dopamine release from rat striatum.
AB  - Recent observations from synaptosome preparations have questioned the
      tetrodotoxin (TTX) insensitivity of nicotine-evoked release in the striatum, a
      characteristic previously considered diagnostic of presynaptically located
      nicotinic acetylcholine receptors (nAChRs). Therefore, we have undertaken a
      comparison of nicotine-evoked dopamine release in the presence of TTX from the
      rat striatum in vitro, using synaptosomes and brain slices, and in vivo, using
      microdialysis. In P2 and Percoll-purified synaptosome preparations, 1.5 microM
      TTX partially inhibited nicotine-evoked [3H]dopamine release by 54% and 37%,
      respectively, whereas in more intact preparations (brain slices and
      microdialysis) TTX completely inhibited mecamylamine-sensitive nicotine
      stimulated dopamine release. These results suggest that caution should be
      exercised in the interpretation of TTX sensitivity of nicotine-evoked responses
      with regard to the location of nAChRs.

PMID- 9025101
TI  - Inhibition of acetylcholine release from presynaptic terminals of skate electric
      organ by calcium channel antagonists: a detailed pharmacological study.
AB  - Release of acetylcholine (ACh) from the presynaptic terminals in skate electric
      organ was tested for its sensitivity to calcium channel antagonists. A
      pharmacological profile was established by measuring inhibition of K(+)
      stimulated release of [3H]ACh from prelabelled tissue slices. Peptide antagonists
      of N-type (omega-conotoxins GVIA and MVIIA) and P-type (omega-agatoxin-IVA)
      channels had no effect, whereas both omega-conotoxins MVIIC and SVIB produced
      concentration-dependent inhibition and could completely block ACh release. omega
      Conotoxin GVIA and omega-agatoxin IVA did not attenuate the block by omega
      conotoxin MVIIC. The inorganic ions, Cd2+ and Ni2+, also produced a full
      inhibition of release (Cd2+ > > Ni2+) and Gd3+ a partial one. Drugs targeting L
      type channels (diltiazem, nifedipine and verapamil) at low microM concentrations
      and a synthetic analogue of the polyamine toxin from funnel web spider venom
      (sFTX) at 1 mM were all non-inhibitory. Inhibition by omega-conotoxins MVIIC
      (IC50 25 nM) and SVIB (IC50 500 nM) was reversible and modulated by external
      concentrations of Ca2+. Inhibitory potency was increased by lowering and
      decreased by elevating external Ca2+. This "antagonistic" effect of Ca2+ was also
      seen with Cd2+ inhibition. The inhibitory potency of omega-conotoxin MVIIC was
      unaffected by predepolarisation. End plate potentials generated by release of
      endogenous ACh in electrically-stimulated slices were also reversibly blocked by
      Cd2+ and omega-conotoxins MVIIC and SVIB but were unaffected by omega-conotoxin
      GVIA and omega-agatoxin IVA. It is concluded that ACh release in skate electric
      organ depends on presynaptic calcium channels which have different
      pharmacological properties from established sub-types.

PMID- 9025103
TI  - Effects of the metabotropic glutamate receptor antagonist MCPG on spatial and
      context-specific learning.
AB  - The effects of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4
      carboxyphenylglycine (MCPG) on performance in a water maze and in context
      specific associative learning were examined in rats previously implanted with
      cannulae. MCPG (20.8 micrograms) injected intraventricularly (i.c.v.) before
      testing impaired the performance of rats in the spatial version of the Morris
      water maze, but 1/10 of this dose did not. Memory retention, evaluated 24 hr post
      training, was also affected by the high dose of MCPG. However, performance in a
      cued version of the water maze was not impaired by the high dose, excluding
      effects of the drug on perceptual faculties. The effects of the MCPG were further
      characterized on performance in another hippocampus-dependent spatial learning
      task, the context-dependent fear conditioning task. MCPG (20.8 micrograms,
      i.c.v.) did not interfere with conditioned freezing to context in this task. For
      comparison, a group of rats was injected with the NMDA receptor blocker MK801.
      MK801 at a dose that disrupted the performance in the spatial version of the
      Morris water maze (0.08 mg/kg), significantly reduced freezing compared to
      controls. These experiments indicate that MCPG-sensitive metabotropic receptors
      may be required for only a restricted subset of spatial learning tasks, while
      NMDA receptors may play an integral role in all spatial learning.

PMID- 9025102
TI  - Muscle-type nicotinic acetylcholine receptor delta subunit determines sensitivity
      to noncompetitive inhibitors, while gamma subunit regulates divalent
      permeability.
AB  - Heterologous expression of nicotinic acetylcholine receptor (nAChR) RNAs in
      Xenopus oocytes was used to examine the structural basis for pharmacological and
      physiological differences between muscle-type and neuronal nAChRs. Neuronal
      nAChRs have a higher permeability to calcium than muscle-type nAChRs and display
      inward rectification. while muscle-type nAChRs have a linear current-voltage
      relation. In addition, neuronal nAChRs are more sensitive to inhibition by a
      class of compounds known as "ganglionic blockers". It has been shown previously
      that neuronal-muscle hybrid receptors show increased sensitivity to the use
      dependent inhibitor of neuronal nAChRs, BTMPS, based on the presence of a
      neuronal beta subunit. In this study, we report that omission of gamma subunit
      RNA has a similar effect. alpha beta delta receptors exhibit prolonged inhibition
      by BTMPS; show a significant permeability to divalent ions, display inward
      rectification and are more sensitive to mecamylamine. However, while
      pharmacological effects are associated with the presence of an additional delta
      subunit, the physiological changes described seem to be associated with the
      presence or absence of a gamma subunit. These results suggest that, for nAChRs,
      as is also the case for non-NMDA ionotropic glutamate receptors, the crucial
      functional property of limiting calcium permeability can be served by a single
      subunit.

PMID- 9025104
TI  - NMDA-receptor contribution to spinal nociceptive reflexes: influence of stimulus
      parameters and of preparatory surgery.
AB  - The contribution of NMDA receptors to nociceptive reflexes has been assessed both
      in awake rats and in electrophysiological tests on alpha-chloralose anaesthetized
      spinalized rats prepared with different degrees of surgery. Single motor unit
      activity was recorded in response to alternating noxious mechanical and
      electrical stimuli applied to one hindpaw, and the results compared with paw
      pressure withdrawal reflexes in awake rats. There was little contribution by NMDA
      receptors to nociceptive paw pinch responses either in awake rats or in rats
      prepared with minimal surgery, but following extensive lumbar surgery the
      contribution increased significantly to a level similar to that seen in the wind
      up component of responses elicited by electrical stimulation. Surgery therefore
      has effects several segments from the sensory input that it generates. It
      enhances the NMDA receptor contribution in responses to some but not all types of
      afferent input.

PMID- 9025105
TI  - Electrophysiological characterisation of the antagonist properties of two novel
      NMDA receptor glycine site antagonists, L-695,902 and L-701,324.
AB  - The pharmacological effects of two novel N-methyl-D-aspartate (NMDA) receptor
      glycine site antagonists, L-701,324 and L-695,902 were examined on whole-cell
      voltage-clamped cells and compared to a prototypic antagonist, 7-chlorokynurenic
      acid. Both L-701,324 and L-695,902 non-competitively antagonised NMDA responses
      elicited in rat cultured cortical neurones, this was shown to be due to a
      competitive interaction at the glycine co-agonist site on the receptor complex
      (Kb values: 19 nM and 2.6 microM, respectively). Inhibition curves for the
      antagonism of responses to combined applications of NMDA and glycine showed that
      both antagonists were devoid of any intrinsic activity i.e. "full" antagonists
      and were, therefore, capable of completely abolishing inward currents. Despite
      this fact, both of these novel antagonists apparently modulated glutamate
      affinity for its recognition site-a property hitherto associated only with
      glycine site partial agonists. Human recombinant NMDA receptors comprising
      NR1a/NR2A and NR1a/NR2B subunits expressed in mouse fibroblast cells were also
      used to determine whether L-701,324 and L-695,902 were capable of discriminating
      between subtypes of NMDA receptor. Inhibition curves to each antagonist showed no
      difference in affinity for either of these subunit assemblies (mK1 values L
      701,324 = 0.005 microM on both assemblies; L-695,902 = 4.37 and 3.7 microM on
      NR1a/NR2A and NR1a/NR2B, respectively). Kinetic analysis of the off-rates of
      antagonism with L-701,324 revealed that the high affinity of this compound
      compared to 7-chlorokynurenic acid were attributable to an exceptionally slow
      dissociation of the antagonist from the receptor.

PMID- 9025106
TI  - Characterisation of the interaction between guanyl nucleotides and AMPA receptors
      in rat brain.
AB  - Guanyl nucleotides inhibit the binding of the AMPA receptor agonists
      [3H]fluorowillardiine and [3H]AMPA and the competitive antagonist [3H]CNQX to rat
      brain cerebrocortical membranes. The rank order of inhibition for each of the
      radioligands tested was GTP > GDP > GMP. The nucleotides CTP and ATP showed no
      effect. GTP inhibition was unaffected by the presence or absence of NaCl and
      MgCl2. Pre-treatment of the membranes with GTP, and its removal before addition
      of radioligand, did not inhibit binding. Quantitative autoradiography
      demonstrated that GTP inhibition occurred throughout the brain. These results are
      consistent with guanyl nucleotides acting at an extracellular site present on all
      AMPA receptor subunits, occupation of which inhibits agonist and antagonist
      binding.

PMID- 9025107
TI  - A modulation of glutamate-induced phosphoinositide breakdown by intracellular pH
      changes.
AB  - The influence of intracellular pH (pHi) changes on the formation of inositol
      phosphate metabolites (IPs) produced by glutamatergic stimulation was studied in
      8-day-old rat brain synaptoneurosomes. For this purpose pHi was measured using
      2',7'-bis-(2-carboxyl)-5,6-carboxyfluorescein (BCECF) fluorimetric assay in
      parallel with the basal and receptor-mediated formations of inositol
      monophosphate (IP1) and inositol bisphosphate (IP2). We found that glutamate (1
      mM), which induces a transient acidification (delta pH = -0.05), produces an
      identical accumulation of IP1 and IP2. K+ (30 mM), which provokes an
      alkalinization of the internal medium (delta pH = +0.22), mainly leads to the
      formation of IP1 metabolites. Paired combinations of glutamate with 1, 5 and 10
      mM NH4+ finally result in an alkalinization of the intrasynaptoneurosomal medium.
      These combinations produce a strong decrease of the IP2 level concomitant with an
      increase of the IP1 formation, compared to the levels of IP1 and IP2 evoked by
      glutamate alone. The total amount of IPs (IP1 + IP2) produced by these
      combinations is not different from that obtained with glutamate alone. Paired
      combinations of carbachol with NH4+ produce an identical alkalinization to that
      produced by NH4+ alone. These combinations produce an increased IP1 accumulation,
      while the IP2 formation is slightly decreased. When the internal medium is
      acidified by diminishing the external concentration of Na+, the ratio IP1/IP2
      produced after metabotropic glutamate receptor (mGluR) activation is shifted to
      lower values, while it is not affected for the muscarinic stimulation. These data
      suggest that the mGluR-associated pathway in synaptoneurosomes is sensitive to
      pHi shifts, while the muscarinic receptor-associated pathway is less altered when
      pHi is manipulated. It may be proposed that pH-sensitive inositol phosphate
      dephosphorylating systems, i.e. phosphatases, are associated with mGluRs in this
      preparation.

PMID- 9025108
TI  - Noradrenaline-induced inositol phosphate formation in rat striatum is mediated by
      alpha 1A-adrenoceptors.
AB  - The aim of this study was to assess the contribution of alpha 1-adrenoceptor
      subtypes to noradrenaline (NA)-induced inositol phosphate formation in rat
      striatum. In cross-chopped slices and in the presence of 10 mM LiCl, NA
      stimulated the accumulation of [3H]inositol phosphates. After 60-min incubation
      with 100 microM NA, [3H]IP1 was the major product detected (82 +/- 3% of total
      [3H]inositol phosphates). Best-fit values for the concentration-response curve
      for NA-induced [3H]IP1 accumulation yielded an EC50 of 9.4 +/- 1.1 microM,
      maximum effect of 210 +/- 3% of basal, and Hill coefficient (nH) of 1.1 +/- 0.1.
      Pre-treatment of the slices for 30 min with the alkylating agent
      chloroethylclonidine (100 microM) failed to decrease significantly the response
      to 100 microM NA. Inhibition curves for four alpha 1-antagonists, (+)
      niguldipine, prazosin, WB-4101 and 5-methylurapidil (5-MU), best-fit to a single
      site model with pKi values of 9.4 ((+)-niguldipine), 9.2 (prazosin and WB-4101)
      and 8.8 (5-MU). The putative alpha 1 D-selective antagonist BMY 7378 reduced the
      response to NA only partially (30 +/- 3% inhibition at 1 microM: pKi 7.24). NA
      induced [3H]IP1 accumulation was significantly reduced (to 20 +/- 9% of controls)
      by Ca2+ removal and increased as the extracellular Ca2+ concentration was raised
      from nominally zero (no added Ca2+) to 1 mM Ca2+. NA-induced [3H]IP1 accumulation
      was reduced by both the non-selective Ca2+ channel blocker Ni2+ (58 +/- 3%
      inhibition at 2 mM) and nimodipine, an antagonist of L-type voltage-operated Ca2+
      channels (77 +/- 4% inhibition at 3 microM). Taken together these results
      indicate that NA-induced inositol phosphate formation in striatal slices is
      mediated by activation of alpha 1A-adrenoceptors coupled to Ca2+ entry and Ca2+
      activation of phospholipase C.

PMID- 9025109
TI  - The spin trap reagent PBN attenuates degeneration of 5-HT neurones in rat brain
      induced by p-chloroamphetamine but not fenfluramine.
AB  - Dark Agouti rats injected with either p-chloroamphetamine (PCA; 2.5 mg/kg i.p.)
      or fenfluramine (15 mg/kg i.p.) had substantial decreases (approximately 50%) in
      the concentration of 5-HT and 5-HIAA and binding of [3H]paroxetine in the
      cerebral cortex 7 days later. This indicates that both compounds had produced
      neurodegeneration of 5-HT axon terminals. Two doses of alpha-phenyl-N-tert-butyl
      nitrone (PBN; 150 mg/kg i.p.) 130 min apart had no effect on cortical 5-HT
      content or [3H]paroxetine binding. However, when PBN (150 mg/ kg) was given 10
      min before and 120 min after PCA (2.5 mg/kg) it attenuated the PCA-induced
      neurodegeneration. In contrast, PBN was without significant effect on the
      fenfluramine-induced damage. Changes in rectal temperature following either the
      neurotoxins or neurotoxins+ PBN were no more than +/-1 degree C of saline
      injected control rats. These data indicate that PCA, like MDMA, probably induces
      neurotoxic degeneration because of the formation of catechol or quinone
      metabolites and subsequent reactive tree radical formation. Such a mechanism does
      not appear to explain fenfluramine-induced damage to 5-HT neurones.

PMID- 9025110
TI  - Biochemical profile of YM992, a novel selective serotonin reuptake inhibitor with
      5-HT2A receptor antagonistic activity.
AB  - YM992, (S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride,
      exhibited the biochemical profile of a selective serotonin (5-HT) reuptake
      inhibitor (SSRI) with 5-HT2A receptor antagonistic activity. YM922 showed the
      same high affinity as fluoxetine against the 5-HT reuptake site (Ki = 21 nM) and
      a similar affinity to that of crazodone against the 5-HT2A receptor (Ki = 86 nM).
      In other receptor binding studies, an affinity for the adrenergic alpha 1
      receptor (Ki = 200 nM) and 5-HT2C receptor (Ki = 680 nM) was observed. In a
      monoamine uptake study, YM992 showed a selective 5-HT uptake inhibition (IC50 =
      0.15 microM), but only very weakly inhibited both noradrenaline (NA) and dopamine
      (DA) uptake (IC50 = 3.1 microM (NA), > 10 microM (DA)). YM992 was also found to
      potently inhibit the aggregation of human platelets (IC50 = 1.9 microM),
      revealing antagonistic activity for the 5-HT2A receptor in vitro. Enhanced
      serotonergic neurotransmission, in particular that mediated by the 5-HT1A
      receptor, has recently been reported to be important in the long-term treatment
      of depressive disorders with antidepressants. In addition, some 5-HT1A receptor
      mediated responses are known to be potentiated by co-administration of 5-HT2A
      receptor antagonists. Thus, YM992, having both selective 5-HT reuptake inhibition
      and 5-HT2A antagonistic activity, might show potent therapeutic activity as a
      novel antidepressant in comparison with conventional SSRIs.

PMID- 9025111
TI  - Serotonin efflux in the rat ventral lateral geniculate nucleus assessed by fast
      cyclic voltammetry is modulated by 5-HT1B and 5-HT1D autoreceptors.
AB  - Fast cyclic voltammetry (FCV) was used to measure electrically stimulated
      monoamine efflux in the rat ventral lateral geniculate nucleus (vLGN). The
      electrochemical characteristics of the released species resembled 5-HT but not
      dopamine or noradrenaline. Amine efflux was abolished by the sodium channel
      blocker tetrodotoxin (0.1 microM), Ro 4-1284 (1.0 microM), the fast-acting
      reserpine analogue, and removal of Ca2+ from the superfusate. Amine efflux was
      unaffected by the monoamine oxidase inhibitor clorgyline (0.1 microM). Of
      paroxetine (0.1 microM), desipramine (50 nM) and vanoxerine (0.5 microM),
      selective blockers of 5-HT, noradrenaline and dopamine uptake respectively, only
      paroxetine increased monoamine efflux (to 194 +/- 25%, mean +/- SEM) and
      prolonged the removal half-life (to 638 +/- 105%). The non-specific 5-HT1
      antagonist methiothepin (0.2 microM) increased 5-HT efflux on long (20 pulses at
      20 Hz) but not short trains (20 pulses at 100 Hz). When tested on pseudo-one
      pulse stimulations (5 pulses, 100 Hz), the selective 5-HT1A agonist 8-OHDPAT (1.0
      microM) had no effect. CP 93129 (0.3 microM), the selective 5-HT1B agonist,
      decreased 5-HT efflux to 37 +/- 4% of control and was antagonised by the 5-HT1B
      blocker isamoltane (0.5 microM) and by the 5-HT1D/B antagonist GR 127935 (50 nM).
      The preferential 5-HT1D agonist sumatriptan (0.5 microM) also decreased 5-HT
      efflux, to 55 +/- 6% and was antagonised by GR 127935 (50 nM) but not isamoltane
      (0.5 microM). These results suggest that 5-HT released in the vLGN can be
      measured by FCV. Furthermore, released 5-HT is taken up by the 5-HT transporter
      and may be under the influence of 5-HT1B and 5-HT1D autoreceptors.

PMID- 9025112
TI  - Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin,
      CCK, gastrin and somatostatin plasma levels in the rat.
AB  - Adult male Sprague-Dawley rats were administered the 5-HT subtype selective
      receptor agonists 8-OH-DPAT (0.5-2.0 mg/kg), buspirone (2-8 mg/kg) (5-HT1A),
      TFMPP (0.125-2.0 mg/kg) (5-HT1B), DOI (0.125-2.0 mg/kg) (5-HT2A) and m-CPBG (1.25
      20.0 mg/kg) (5-HT3), subcutaneously. Oxytocin, cholecystokinin (CCK),
      somatostatin and gastrin plasma levels were determined by standard RIA techniques
      30 and 120 min after injection of the respective 5-HT receptor agonist. It was
      found that the 5-HT1A and the 5-HT2A/C, but not the 5-HT2B or the 5-HT3 receptor
      agonists produced an increase in plasma oxytocin levels and these effects were,
      at least partially, antagonized by the corresponding subtype selective
      antagonists (-)pindolol (2 mg/kg) and ritanserin (2 mg/kg), respectively,
      administered 10 min before 8-OH-DPAT (0.5 mg/kg) or DOI (0.5 mg/kg). The maximal
      response to the 5-HT1A receptor agonists (approx. 120 nmol/l) was from 8 to 5
      times the maximal response to the 5-HT2A C receptor agonist. In addition, 8-OH
      DPAT and DOI caused a decrease in plasma CCK levels, whereas the 5-HT1B receptor
      agonist TFMPP gave rise to an increase in plasma CCK levels. There were no
      statistically significant effects by any of the 5-HT receptor agonists on plasma
      somatostatin or gastrin levels under the present conditions. It is suggested that
      the clinical effects of new anxiolytic 5-HT1A receptor agonists, such as
      buspirone, to an extent may be mediated via an increased release of oxytocin.

PMID- 9025113
TI  - Cyclic GMP inhibition of metabotropic glutamate receptor-induced phosphoinositide
      hydrolysis in mesencephalic neurons.
AB  - The effect of cGMP on metabotropic glutamate receptor-induced stimulation of
      phosphoinositide hydrolysis in mesencephalic neuronal cultures was evaluated by
      cell incubation with the stable analogue dibutyryl-cGMP (10 microM). A complete
      blockade of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid- or quisqualate
      induced inositol phosphate formation was observed. Ionotropic glutamate receptors
      in mesencephalic neurons activate cGMP formation and, through this intracellular
      messenger, they might control mGluR activity.

PMID- 9025114
TI  - 5-HT1A receptors are not involved in clozapine's lack of cataleptogenic
      potential.
AB  - Clozapine and 8-OH-DPAT antagonized haloperidol-induced catalepsy in rats (ED50
      10 and 0.1 mg/kg s.c., respectively). Whereas the selective 5-HT1A receptor
      antagonist WAY 100635 (0.1 mg/kg s.c.) completely antagonized the inhibitory
      effect of 8-OH-DPAT, clozapine's effect was not affected. On the other hand,
      clozapine and 8-OH-DPAT inhibited ultrasonic vocalization in rats (ED50 0.7 and
      0.03 mg/kg s.c., respectively), which effects were antagonized by WAY 100635. The
      lack of catalepsy of clozapine, therefore, cannot be addressed primarily to
      clozapine's agonistic activity at 5-HT1A receptors.

PMID- 9025115
TI  - Functional activation of the human brain during mental rotation.
AB  - Regional cerebral blood flow was measured with positron emission tomography
      during the performance of tasks that required cognitive spatial transformations
      of alphanumeric stimuli. In the mirror image task, the subjects were required to
      discriminate between the normal and the mirror images of alphanumeric stimuli
      presented in the upright orientation. In the mental rotation task, the same
      judgement was required, but now the stimuli were presented in various
      orientations other than the upright one. The subjects therefore had to rotate the
      stimuli, in mind, into the upright position before making their decision. In
      relation to the control task, which involved discrimination of these same stimuli
      but not any form of mental transformation, there were significant increases in
      the right postero-superior parietal cortex and the left inferior parietal cortex
      in both experimental tasks. For mental rotation, specific activity was seen only
      within the left inferior parietal region and the right head of the caudate
      nucleus. These results specified the parietal areas involved in a purely
      cognitive spatial process and demonstrated a close interaction between these
      areas and the anterior neostriatum and certain lateral frontal cortical areas in
      the discrimination of rotated forms of stimuli.

PMID- 9025116
TI  - Event-related potentials and the recognition memory exclusion task.
AB  - Subjects heard words that were presented in either a male or a female voice, and
      were required to perform one of two encoding tasks according to the gender of the
      voice. At test studied words were presented visually, along with a set of words
      new to the experiment. Subjects were required to respond on one key to words
      belonging to one of the two classes of studied word (targets), and to respond on
      a different key both to words belonging to the other study class (non-targets),
      and to words new to the experiment. In comparison to the event-related potentials
      (ERPs) elicited by new words, the ERPs elicited by correctly detected targets
      exhibited two temporally and topographically distinct positive going effects: one
      of these was phasic, showed a parietal maximum, and was larger over the left than
      the right hemisphere. The second effect was more sustained in time, frontally
      distributed, and was larger over the right hemisphere. The ERPs elicited by
      correctly classified non-targets contained the parietal effect only. These
      findings confirm that retrieval of contextual information in tests of recognition
      memory (recollection) is associated with two distinct ERP modulations. While one
      of these may be closely tied to process necessary for recollection, the other may
      reflect less obligatory processes which operate on the products of successful
      retrieval.

PMID- 9025117
TI  - Dissociations between memory for temporal order and recognition memory in aging.
AB  - Young and old subjects participated in an experiment in which trials testing
      memory for temporal order (recency memory) and recognition memory were randomly
      intermixed with study trials in a continuous sequence. A dissociation was found
      between recency and recognition memory performance for pictorial stimuli.
      Relative to young adults, older adults performed at chance on recency memory
      trials whereas they were not impaired on recognition memory. Recency performance
      was correlated with measures derived from the Wisconsin Card Sorting test,
      whereas recognition performance was not. The results are discussed in terms of
      the role of the frontal lobes in temporal-order memory and of possible frontal
      lobe deterioration in normal aging.

PMID- 9025118
TI  - Haptic discrimination in capuchin monkeys (Cebus apella): evidence of manual
      specialization.
AB  - Two experiments investigated the effects of haptic and visual discrimination on
      hand preference in 22 brown capuchin monkeys (Cebus apella). The percentage of
      left-handed subjects in Experiment 1 were 63.6%, 45.5%, and 18.2% for haptic,
      bipedal, and quadrupedal reaching, respectively. In Experiment 2, the haptic
      demands of the task were manipulated by using additional food types and another
      tactile medium. Left-hand preferences were further strengthened when reaching
      into water compared to pineshavings in Experiment 1. Reaching with no tactile
      interference resulted in equal numbers of lateralized and nonlateralized
      subjects. These results show that when reaching demands the use of haptic cues,
      as opposed to visual ones, monkeys shift towards greater left hand use. This is
      consistent with what is known about right hemisphere superiority for haptic
      discrimination in humans.

PMID- 9025119
TI  - Agnosia for object orientation: implications for theories of object recognition.
AB  - Instances in which objects are copied accurately, but are dramatically rotated
      relative to the original, have been interpreted as evidence for viewpoint
      independent accounts of the object recognition process. In two case reports, we
      demonstrate that patients who show rotation in copying also show difficulties in
      informing the examiner of the canonical orientation of known objects. In copying
      rotated versions of familiar objects, one subject showed a tendency to copy them
      in their canonical upright orientation, and both subjects copied non
      representational line drawings with their principal axis vertically aligned, and
      with the irregular end pointing 'upwards'.

PMID- 9025120
TI  - Covert visual spatial attention in boys with attention deficit hyperactivity
      disorder: lateral effects, methylphenidate response and results for parents.
AB  - We report three related studies of covert visual spatial orienting in child
      attention deficit hyperactivity disorder (ADHD). In Study 1, we examined covert
      visual spatial orienting in ADHD and comparison boys, Study 2 comprised a dose
      response study of methylphenidate for the ADHD group, and Study 3 was an
      investigation of biological and adoptive parents. In contrast with comparison
      subjects (n = 17). ADHD boys aged 6-12 (n = 27) showed both slower reaction times
      overall and within-condition (lateral) asymmetries in reaction times.
      Specifically, boys with ADHD reacted more slowly to uncued targets in the left
      visual field than in the right visual field. Responses to stimuli in the two
      visual fields were differentially affected by methylphenidate for the ADHD group.
      Medication equalized visual field responses to the uncued targets, resulting in a
      significant cue x dose x visual field interaction. Further, medication altered
      the relative cue responsivity in the two visual fields, resulting in a
      significant dose x visual field interaction for the Validity Effect. Biological
      parents of ADHD boys (n = 16) also showed slower reaction times to uncued left
      visual field targets than to right visual field targets; in addition they showed
      slower response to invalidity cued targets in the right visual field. These
      literal effects were not observed in adoptive parents of ADHD boys (n = 12) or
      biological parents of comparison boys (n = 14). Possible abnormal hemispheric
      asymmetry of attention functions in boys with ADHD and their biological parents
      is discussed.

PMID- 9025121
TI  - Lateral advantages in same-different comparison of two-note, dichotically
      presented chords to a successively-presented probe.
AB  - An experiment is reported which examines same-different comparison of
      dichotically presented, two-tone chords to a probe. A prediction of a fast 'same'
      response indicative of holistic processing was tested. Stimuli and probes were
      systematically related by similarity relationships established in a previous
      experiment. No evidence was found for fast 'same' responding overall or on either
      ear, but a right ear advantage for the making of difficult 'different' decisions
      was found for accuracy. It is argued that the concepts of analytic and holistic
      processing may require some redefinition and a preliminary account is offered in
      terms of Krueger's [23] noisy operator model.

PMID- 9025122
TI  - Tapping, talking and the thalamus: possible influence of the intralaminar nuclei
      on basal ganglia function.
AB  - A patient with a discrete lesion of the left, intralaminar thalamic, nuclei
      exhibited a paradoxical finding with regard to finger-tapping. Normal subjects
      typically reduce their tapping rate when performing simultaneous verbal activity.
      Tapping was impaired in our patient's contralesional hand on baseline trials;
      however, performing the controlled oral word association (COWA) task, while
      finger-tapping, normalized her deficit. Subsequent experiments showed that
      motoric tasks rather than cognitive aspects of the COWA task were critical in
      potentiating finger-tapping performance. A SPECT study performed at rest revealed
      focal perfusion asymmetries in motor and premotor cortices. Because the caudal
      intralaminar nuclei project heavily to the striatum, striatal deafferentiation
      may account for these asymmetries. These observations provide some insight into
      the influences of the caudal intralaminar thalamic nuclei on basal ganglia
      function and the basal ganglia's influence on motor gating.

PMID- 9025123
TI  - Multiple visuospatial working memory buffers: evidence from spatiotemporal
      patterns of brain activity.
AB  - Numerous studies have shown that the visual system involves different cortical
      pathways in the perception of object (ventral visual pathway) and spatial (dorsal
      visual pathway) information. The present study was concerned with whether human
      visuospatial working memory divides along similar lines. We used event-related
      brain potentials (ERPs) recorded from scalp of normal humans to show the
      existence of different buffering systems for the retention of object and spatial
      visual information. Subjects were presented with object or spatial stimuli to be
      retained for a 3.6-sec interval. The ERPs isolated brain activity associated with
      retention from earlier storage and later retrieval processes. The ERP scalp
      topographies indicated that the underlying patterns of brain activation were
      different during retention of object and spatial information.

PMID- 9025124
TI  - Lexical-semantic deficits in two patients with dominant thalamic infarction.
AB  - Two patients with dominant thalamic infarction, one in the tuberothalamic artery
      territory, the other in the paramedian artery territory, demonstrated language
      impairment limited to word retrieval difficulties in spontaneous language and
      structured naming tasks. Using a cognitive neuropsychological model of lexical
      processing developed in the study of patients with cortical lesions. We carried
      out a detailed investigation of their lexical abilities. Both patients
      demonstrated impairment restricted to oral and written picture naming and oral
      naming to definition and spared performance on tasks of lexical comprehension,
      oral word reading, and writing to dictation, as well as syntactic comprehension
      and production. Naming impairment disproportionately affected lower frequency
      words, and word substitutions often corresponded to objects that were
      semantically-related to target words. We propose that our patients' word
      retrieval impairments reflect a failure of thalamic input to effectively engage
      the cortical networks subserving lexical semantic processing, leading to degraded
      levels of activation as the semantic system interfaces with subsequent stages of
      lexical processing.

PMID- 9025125
TI  - Firm myocardium in cardiopulmonary resuscitation.
AB  - Firm myocardium in cardiopulmonary resuscitation (CPR) is a rarely described yet
      potentially important condition. To investigate the clinical nature and
      implications of firm myocardium in CPR, we retrospectively analyzed 59 adult
      patients with nontraumatic out-of-hospital cardiac arrest who underwent open
      chest CPR in the emergency department and had heart consistency recorded.
      Consistency of the myocardium varied considerably between patients. Firm
      myocardium was noticed in 36 cases, mainly in the left ventricle (firm myocardium
      group). The remaining 23 hearts were not firm (soft myocardium group). Some
      hearts had an increase in their consistency during CPR. Patient characteristics
      were similar in the two groups. The firm myocardium group showed greater base
      deficit on arterial blood gas analysis, suggesting more severe ischemic injury.
      Very firm heart had a close association with an extremely low end-tidal CO2
      tension. Histopathological examination revealed hypertrophy and fibrosis common
      to the two groups. Both groups received similar treatment except for a shorter
      duration of direct cardiac massage in the firm myocardium group, although a
      reasonably prolonged effort was made in most cases. The firm myocardium group
      responded poorly to treatment. Very firm myocardium never contracted, whereas
      less firm myocardium usually showed some, albeit insufficient, activity. Most
      cases in the soft myocardium group regained a pulse. Our results suggest that
      firm myocardium: (1) is common in patients who receive CPR in the emergency
      department, (2) indicates ischemic contracture, (3) is not uniform in firmness,
      reflecting the degree of ischemia and (4) is a grave prognostic factor in cardiac
      resuscitation.

PMID- 9025126
TI  - Checking the carotid pulse check: diagnostic accuracy of first responders in
      patients with and without a pulse.
AB  - International guidelines for cardiopulmonary resuscitation (CPR) in adults
      advocate that cardiac arrest be recognized within 5-10 s, by the absence of a
      pulse in the carotid arteries. However, validation of first responders'
      assessment of the carotid pulse has begun only recently. We aimed (1) to develop
      a methodology to study diagnostic accuracy in detecting the presence or absence
      of the carotid pulse in unresponsive patients, and (2) to evaluate diagnostic
      accuracy and time required by first responders to assess the carotid pulse. In 16
      patients undergoing coronary artery bypass grafting, four groups of first
      responders (EMT-1: 107 laypersons with basic life support (BLS) training; EMT-2:
      16 emergency medical technicians (EMTs) in training; PM-1: 74 paramedics in
      training; PM-2: 9 certified paramedics) performed, single-blinded and randomly
      allocated, carotid pulse assessment either during spontaneous circulation, or
      during non-pulsatile cardiopulmonary bypass. Time to diagnosis of carotid pulse
      status, concurrent haemodynamics and diagnostic accuracy were recorded. In 10%
      (6/59), an absent carotid pulse was not recognized as pulselessness. In 45%
      (66/147), a pulse was not identified despite a carotid pulse with a systolic
      pressure > or = 80 mmHg. Thus, although sensitivity of all participants for
      central pulselessness approached 90%, specificity was only 55%. Both sensitivity
      and, to a lesser degree, specificity improved with increasing training; blood
      pressure or heart rate had no significant effect. The median diagnostic delay was
      24 s (minimum 3 s). When no carotid pulse was found, delays were significantly
      longer (30 s: minimum 13 s), than when a carotid pulse was identified (15 s;
      minimum 3 s) (P < 0.0001). Of all participants, only 15% (31/206) produced
      correct diagnoses within 10 s. Only 1/59 (2%) identified pulselessness correctly
      within 10 s. Our cardiopulmonary bypass model of carotid pulse assessment proved
      to be feasible and realistic. We conclude that recognition of pulselessness by
      rescuers with basic CPR training is time-consuming and inaccurate. Both intensive
      retraining of professional rescuers and reconsideration of guidelines about
      carotid pulse assessment are warranted.

PMID- 9025127
TI  - ACD versus standard CPR in a prehospital setting.
AB  - BACKGROUND: Animal and human studies in cardiac arrest demonstrate significant
      improvements in systolic blood pressure, coronary perfusion pressure and total
      brain and myocardial blood flow with active compression-decompression (ACD)
      cardiopulmonary resuscitation (CPR). The results of recent studies in patients
      with out-of-hospital cardiac arrest and use of ACD-CPR are non-uniform and
      require supplementation. METHODS: In a retrospective non-randomised design, 152
      adult patients with prehospital cardiac arrest, not caused by trauma or
      hypothermia, were studied. Compressions were performed according to the
      recommendations of the American Heart Association. Three ACD devices were
      assigned to seven rescue units changing monthly. Study end-points were the rates
      of return of spontaneous circulation (ROSC), admission to hospital, survival at
      24h, hospital discharge and neurologic outcome. RESULTS: 70 (46%) patients
      underwent standard (STD) CPR and 82 (54%) patients were treated with ACD-CPR.
      Both groups were comparable with regard to age, sex, witnessed cardiac arrests,
      bystander CPR, cause of arrest, time intervals, number of defibrillations, and
      total amount of epinephrine. No significant differences in outcome could be
      found: 20 patients (29%) who received STD-CPR, and 14 patients (17%) who
      underwent ACD-CPR survived to hospital discharge. Neither at other end-points nor
      in any subgroups could any significant differences be discovered. Patients
      regaining ROSC showed a significant difference in favour of STD-CPR for the end
      points of hospital admission, 24-h survival and hospital discharge. CONCLUSION:
      No significant differences in hospital discharge and neurological outcome were
      found between STD-CPR and ACD-CPR.

PMID- 9025128
TI  - Active compression-decompression resuscitation: a prospective, randomized study
      in a two-tiered EMS system with physicians in the field.
AB  - Improved cardiopulmonary circulation with active compression-decompression
      cardiopulmonary resuscitation (ACD-CPR) has been demonstrated in studies using
      different animal models and a small number of humans in cardiac arrest (CA).
      However, prehospital studies have shown both positive and no extra benefit of ACD
      CPR on return of spontaneous circulation (ROSC), hospital admission and discharge
      rates. The aim of our prospective study was to compare standard manual CPR (S
      CPR) with ACD-CPR as the initial technique of resuscitating patients with out-of
      hospital CA, with respect to survival rates and neurological outcome. Patients
      with out-of-hospital CA treated by emergency medical services (EMS) personnel
      were randomly assigned to one of two groups (ACD-CPR versus S-CPR). Time
      intervals to key measures were documented by means of on-line tape-recording.
      Neurological outcome was assessed using standard scoring systems (cerebral and
      overall performance categories (CPC and OPC)). A total of 220 patients (S-CPR, n
      = 114: ACD-CPR, n = 106) were included in the study in a random order. The
      treatment groups were similar with respect to age, sex, time interval from
      collapse to CPR, defibrillation and first adrenaline medication. There was no
      difference between the ACD group and the standard CPR group in terms of ROSC
      (50.9% vs. 59.6%), hospital admission (33% vs. 33.3%), hospital discharge (16%
      vs. 14%), or CPC and OPC (1.82 vs. 2.13 and 2.06 vs. 2.25, respectively).
      Concerning complications of CPR, there was no difference between the groups. In
      our two-tiered EMS system with physician-staffed ambulances, ACD-CPR neither
      improved nor impaired survival rates and neurological prognosis in patients with
      out-of-hospital cardiac arrest. The new CPR technique did not increase the
      complications associated with the resuscitation effort.

PMID- 9025129
TI  - Rescuer's work capacity and duration of cardiopulmonary resuscitation.
AB  - Specific training in the techniques of cardiopulmonary resuscitation (CPR) has
      been the major aim of CPR education for both health care professionals and lay
      people over the past few decades. We performed a randomized trial to evaluate
      individual physiological parameters of 12 professional rescuers influencing
      duration and quality of standard CPR and active compression-decompression CPR.
      CPR duration was assessed according to individual work capacity after grouping
      rescuers as untrained and trained individuals, according to their work capacity
      of up to and including 100% and over 100%. The average work capacity of all the
      rescuers was determined by incremental exercise testing, resulting in 110.0 +/-
      26.5% compared with data for the normal population. With 29.3 +/- 12.8 min
      duration, standard CPR was significantly longer than active compression
      decompression CPR with 15.5 +/- 10.2 min duration (P = 0.009). No changes in the
      forces of compression and decompression were measured during active compression
      decompression CPR, thus demonstrating maintenance of constant CPR quality.
      Duration of resuscitation was influenced by the CPR method performed and by the
      individual work capacity (P = 0.004 and P = 0.027, respectively). We conclude
      that the duration of CPR depends both on the method applied and the rescuers'
      individual work capacity and recommend improvement of work capacity by aerobic
      training especially for professional rescuers.

PMID- 9025130
TI  - Community cardiac awareness teaching in a rural area: the potential for a health
      promotion message.
AB  - Little information has been published on the uptake of cardiopulmonary
      resuscitation (CPR) training in rural areas or on the potential to associate a
      health promotion message with skills training. This paper describes CPR
      instructor and community training programmes in Ireland. Public interest in these
      programmes has been strongest in rural areas, which have constituted the main
      focus of activity to date. High-quality training of lay instructors has been a
      specific target of the programmes, which have included a significant health
      promotion message. In the pilot rural area, almost 2% of adults aged between 15
      and 64 years attended a course during the first year of operation. However, the
      self-reported risk factor profile of participants suggests significant under
      estimation of risk factors such as obesity, hypertension or raised blood
      cholesterol. While general population teaching programmes can attract large
      numbers of participants, even in isolated rural areas, the perceived relevance of
      an associated health promotion message may be very low.

PMID- 9025131
TI  - Ventricular fibrillation in a swine model of acute pediatric asphyxial cardiac
      arrest.
AB  - STUDY OBJECTIVE: To determine cardiac rhythms in a swine model of acute pediatric
      asphyxial cardiac arrest. DESIGN: Prospective electrocardiographic evaluation of
      36 piglets. SETTING: University hospital laboratory. INTERVENTION: Piglets were
      acutely asphyxiated by endotracheal tube clamping until 10 min after loss of
      aortic pulsations. Resuscitative efforts were then provided. RESULTS: None of the
      animals had ventricular fibrillation (VF) when loss of aortic pulsations occurred
      (11 +/- 2 min after clamping). Fourteen of the 36 piglets exhibited VF during the
      asphyxial insult. VF converted to asystole in four piglets prior to
      resuscitation. Immediately prior to resuscitation, VF occurred in 10 piglets,
      asystole in 19 piglets, and bradyarrhythmias in seven piglets. CONCLUSION: VF
      occurs frequently in this piglet model of prolonged asphyxial cardiac arrest,
      consistent with recent observations in pediatric prehospital cardiac arrests. VF
      occurred late in the asphyxial process.

PMID- 9025132
TI  - Spectral analysis of ventricular fibrillation and closed-chest cardiopulmonary
      resuscitation.
AB  - This study was designed to assess the interference by closed-chest
      cardiopulmonary resuscitation (CPR) on the ventricular fibrillation (VF) ECG
      signal in a porcine model of cardiac arrest and to elucidate which variable of VF
      spectral analysis reflects best myocardial blood flow and resuscitation success
      during CPR. Fourteen domestic pigs were allocated to receive either 0.4 U/kg
      vasopressin (n = 7) or 10 ml saline (n = 7) after 4 min of VF and 3 min of CPR.
      Using radiolabeled microspheres, myocardial blood flow was determined during CPR
      before, and 90 s and 5 min after, drug administration. Using spectral analysis of
      VF, the median frequency, dominant frequency, edge frequency and amplitude of VF
      were determined simultaneously and before the first defibrillation attempt. Using
      filters in order to specify frequency ranges, stepwise elimination of mechanical
      artifacts resulting from CPR revealed that at a frequency bandpass of 4.3-35 Hz,
      median fibrillation frequency has a sensitivity, specificity, positive and
      negative predictive value of 100% to differentiate between resuscitated and non
      resuscitated animals. The best correlation between myocardial blood flow and
      fibrillation frequency was found at a median frequency range of 4.3-35 Hz. We
      conclude that spectral analysis of VF can provide reliable information relating
      to successful resuscitation. In this model after elimination of oscillations due
      to mechanical CPR, median fibrillation frequency best reflects the probability of
      resuscitation success.

PMID- 9025133
TI  - Future directions for resuscitation research. IV. Innovative advanced life
      support pharmacology.
AB  - The topics discussed in this session include a partial review of laboratory and
      clinical studies examining the effects of adrenergic agonists on restoration of
      spontaneous circulation after cardiac arrest, the effects of varying doses of
      epinephrine, and the effects of novel vasopressors, buffer agents (NaHCO3, THAM,
      'Carbicarb') and anti-arrhythmics (lidocaine, bretylium, amiodarone) in
      refractory ventricular fibrillation. Novel therapeutic approaches include
      titrating electric countershocks against electrocardiographic power spectra and
      of preceding the first countershocks with single or multiple drug treatments.
      These approaches need to be investigated further in controlled animal and patient
      studies. Epidemiologic data from randomized clinical outcome studies can give
      clues, but cannot document pharmacologic mechanisms in the dynamically changing
      events during attempts to achieve restoration of spontaneous circulation from
      prolonged cardiac arrest. Also, rapid drug administration by the intraosseous
      route was compared with intratracheal and intravenous (i.v.) drug administration.
      Many studies on the above treatments have yielded conflicting results because of
      differences between healthy hearts of animals and sick hearts of patients,
      differences in arrest (no-flow) times and cardiopulmonary resuscitation (CPR)
      (low-flow) times, different pharmacokinetics, different dose/response
      requirements, and different timing of drug administration during low-flow CPR
      versus during spontaneous circulation. The need to stabilize normotension and
      prevent rearrest by titrated novel drug administration, once spontaneous
      circulation has been restored, requires research. Most of the above topics
      require some re-evaluation in clinically realistic animal models and in cardiac
      arrest patients, especially by titration of old and new drug treatments against
      variables that can be monitored continuously during resuscitation.

PMID- 9025134
TI  - The effect of experience of on-site physicians on survival from prehospital
      cardiac arrest.

PMID- 9025135
TI  - Basic framework for the economic evaluation of animal health control programmes.
AB  - The further integration of international markets means that co-ordinated policies
      against contagious animal infections have become increasingly important, and
      stricter demands for control and eradication should be expected in the future. To
      meet these demands, it would be desirable to create a computer simulation
      environment in which 'what if?' scenarios could be performed, in order to explore
      the epidemiological and economic effects of various infections and control
      strategies. The authors propose a flexible economic framework and illustrate this
      framework with an example. The framework has four elements: changes in the
      percentage of infectious herds, changes in product quantities, changes in product
      prices and economic integration. Each element is specifically defined and has its
      own input and output data, depending on the control strategy under consideration.
      In an illustration of the framework, probability distributions of the different
      control strategies are compared and the optimal strategy is chosen, according to
      the attitude of the decision-maker towards risk. Such a framework can be
      considered as a new standardised approach for comparing and selecting animal
      health control strategies, by integrating technical and economic data and
      principles.

PMID- 9025136
TI  - The nature of animal health economics in relation to veterinary epidemiology.
AB  - Animal health economics is being formally integrated into such institutions as
      sub-Saharan African universities and Veterinary Services. Unfortunately, the
      nature of the relationship between economics and epidemiology is not clearly
      understood. Economics has an extensive theoretical apparatus and an array of
      methods and techniques. Animal health economics has two interrelated branches:
      economics for the planning and management of animal health services and economic
      analysis of diseases and interventions. Epidemiology and economics, although
      separate scientific areas, are complementary when the goal is efficient
      management of animal health and associated delivery systems. In performing
      economic analyses, an "economic model' should determine data requirements
      (epidemiological and socioeconomic), as such analyses invariably require
      epidemiological inputs. The core concepts in economic analysis are as follows:
      conceptual models, opportunity cost of resources, marginal analysis and partial
      analysis. Important methods include statistical models, mathematical programming,
      budgets, cost minimisation, decision analysis, variants of cost-benefit analysis
      and simulation. Given the nature of animal health economics, veterinarians who
      want to practise as economists need a thorough training in economic principles
      and methods, in addition to training in basic epidemiology.

PMID- 9025137
TI  - A review of the epidemiology of scrapie in sheep.
AB  - The aim of this review is to summarise and evaluate the data available about the
      aetiology of scrapie in naturally affected sheep flocks, particularly data
      concerning the possible transmission of infection between related animals. The
      author examines data taken from various relevant studies carried out over the
      last thirty years. The main conclusions are that scrapie is an infectious disease
      with a genetic influence on the incubation period. The increased risk of disease
      in the offspring of affected animals is thought to be largely the result of
      increased genetic susceptibility, with a large proportion of the cases occurring
      in high-incidence flocks being the result of horizontal transmission of
      infection.

PMID- 9025138
TI  - Research and technological developments required for more rapid control and
      eradication of foot and mouth disease.
AB  - Foot and mouth disease (FMD) is the major disease barrier to international trade
      in animals and animal products. Countries free of the disease take severe
      measures to exclude the virus, to avoid the potentially devastating consequences
      of an outbreak, particularly for the animal export trade. Consequently, FMD-free
      countries either refuse to trade with sporadically or endemically infected
      countries, or else apply stringent and often expensive safeguards before agreeing
      to import animals or animal products. Technological advances can assist countries
      which are free of FMD to maintain this status. Such advances also aid countries
      in which the disease is sporadic or endemic, by accelerating the progress of
      control and eradication programmes. The authors review recent advances in tests
      for the diagnosis of FMD, in addition to advances in surveillance, vaccinology
      and information technology, i.e. computing and networking. Furthermore, the
      authors examine the application of these advances to improve programmes for the
      control and eradication of FMD, and identify the requirements for further
      research into the disease.

PMID- 9025139
TI  - Comparison of a radioactive and non-radioactive method for sequencing foot and
      mouth disease virus isolates.
AB  - The authors compare the radioactive method of detecting foot and mouth disease
      virus sequence products with a non-radioactive, silver stain sequencing method.
      The latter was found to compare favourably to the radioactive technique for
      detecting such products. The silver stain sequencing method was simple and did
      not require expensive specialised equipment. This new approach will be
      particularly useful in developing countries, since the method does not depend on
      the availability of fresh radioactive isotopes and is also safer and considerably
      cheaper.

PMID- 9025140
TI  - Natural and vaccine-induced immunity to foot and mouth disease: the prospects for
      improved vaccines.
AB  - The review considers both the immune responses of livestock to foot and mouth
      disease (FMD) virus after infection or vaccination, and the characteristics and
      properties of FMD viruses and vaccines which are relevant to protection.
      Particular attention is given to possible approaches which could be used to
      improve conventional vaccines or produce novel vaccines against this most
      important disease.

PMID- 9025141
TI  - The performance of southern African territories serotypes of foot and mouth
      disease antigen in oil-adjuvanted vaccines.
AB  - The performance of selected oil adjuvants containing Southern African Territories
      (SAT) serotypes of foot and mouth disease virus was assayed by testing antibody
      levels elicited in cattle, sheep and goats, and by testing protection of cattle
      on challenge. Various oil adjuvant formulations were tested initially in cattle
      and guinea pigs, and compared with a standard alhydrogel and saponin-based (AS)
      vaccine. A commercial double oil emulsion vaccine elicited higher antibody titres
      and a more prolonged antibody response than the conventional AS vaccine, than a
      commercial single emulsion oil formulation or an incomplete Freund's adjuvant
      formulation. Incomplete Freund's adjuvant was selected for the formulation of a
      trivalent vaccine which was assayed in cattle, sheep and goats for antibody
      response and local reactions. The double oil emulsion elicited a high level of
      antibodies, which was maintained for at least six months after a single
      inoculation. The product was easily injectable and did not cause local or
      systemic reactions.

PMID- 9025142
TI  - Rift Valley fever in Nigeria: infections in humans.
AB  - Between 1985 and 1989, a total of 3,121 human sera collected from different
      population groups in six ecological zones of Nigeria were tested for the presence
      of antibodies to Rift Valley fever (RVF) virus by the haemagglutination
      inhibition test. All reactive sera were further tested by the plaque reduction
      neutralisation test and specific RVF immunoglobulin M (IgM) assay. A total of 461
      sera (14.8%) demonstrated haemagglutination-inhibiting antibody and 390 of the
      461 initially reactive sera (84.6%) revealed neutralising antibodies. A
      significantly higher exposure to the virus was found among livestock workers and
      wildlife rangers than in other categories of people tested. The rate of positive
      reactions was higher in adults of 30 years or more than in younger age groups. Of
      461 sera tested for specific RVF IgM, 107 gave positive results (23.2%). The
      highest prevalence of RVF IgM was found among livestock and forestry workers. In
      the longitudinal survey, an RVF virus infection rate of 6.7% was demonstrated.
      The infection rate was significantly higher during the wet season than during the
      dry season of the same year.

PMID- 9025143
TI  - Rift Valley fever in Nigeria: infections in domestic animals.
AB  - Between 1986 and 1989, 2,255 sera collected from six domestic animal species in
      Nigeria were tested for antibodies to Rift Valley fever (RVF) virus. In addition,
      a longitudinal study was carried out from July 1987 to December 1988, using ten
      sentinel flocks on four farms at Ibadan and Ile-Ife, to determine the activity of
      RVF virus (RVFV). All samples were tested for haemagglutination-inhibiting
      antibodies and positive sera were further screened, using the plaque reduction
      neutralisation test. Of 2,255 samples, 259 (11.5%) had haemagglutination
      inhibiting and neutralising antibodies, as follows: sheep (18.7%), goats (10.4%),
      cattle (10.2%), horses (9.8%) and camels (3.3%). The highest prevalence of RVFV
      antibody was found in the plateau area (18.4%). Animals aged three years or more
      had a higher prevalence of antibodies to RVFV. Longitudinal studies showed
      seroconversion to RVFV in ten of the 210 animals which were kept under
      observation (4.8%). All seroconversions occurred during the wet season. The
      results of this study indicate that the infection of animals with RVFV is
      widespread in Nigeria.

PMID- 9025144
TI  - Field use of a vaccinia-rabies recombinant vaccine for the control of sylvatic
      rabies in Europe and North America.
AB  - During recent years, most research on the control of sylvatic rabies has
      concentrated on developing methods of oral vaccination of wild rabies vectors. To
      improve both the safety and the stability of the vaccine used, a recombinant
      vaccinia virus, which expresses the immunising glycoprotein of rabies virus
      (VRG), has been developed and tested extensively in the laboratory as well as in
      the field. From 1989 to 1995, approximately 8.5 million VRG vaccine doses were
      dispersed in Western Europe to vaccinate red foxes (Vulpes vulpes), and in the
      United States of America (USA) to vaccinate raccoons (Procyon lotor) and coyotes
      (Canis latrans). In Europe, the use of VRG has led to the elimination of sylvatic
      rabies from large areas of land, which have consequently been freed from the need
      for vaccination. Nevertheless, despite very good examples of cross-border
      cooperation, reinfections have occurred in some regions, due to the difficulty of
      co-ordinating vaccination plans among neighbouring countries. In the USA,
      preliminary data from field trails indicate a significant reduction in the
      incidence of rabies in vaccinated areas.

PMID- 9025145
TI  - Tuberculosis in sea lions and fur seals from the south-western Atlantic coast.
AB  - Diverse pathological conditions causing the strandings and/or deaths of several
      species of sea lions and seals on the northern coast of the province of Buenos
      Aires are being studied. Tuberculosis was diagnosed in six cases of strandings,
      involving two otariid seal species (one Otaria flavescens and five Arctocephalus
      australis), between March 1989 and December 1992. Necropsies were performed on
      all six cases. Granulomatous lesions were observed in the prescapular and hepatic
      lymph nodes. Lesions were also seen in the lungs, pleura, liver, spleen and
      peritoneum. Bacteriological isolation was attempted from all the samples. The
      isolates were identified as belonging to the Mycobacterium tuberculosis complex.
      Some showed characteristics consistent with M. bovis, whereas others demonstrated
      properties of M. tuberculosis. Genomic deoxyribonucleic acid (DNA) from these
      strains was analysed by restriction fragment length polymorphism (RFLP), using
      IS6110, a genetic marker found only in the Mycobacterium tuberculosis complex.
      Using the IS6110 probe, similar fingerprints were obtained, suggesting a common
      source of infection. However, the pattern of DNA differed from DNA patterns of M.
      bovis isolated from humans and cattle in Argentina, which generally contain a
      unique 1.9 kbp band. These results suggest that mycobacteria isolated from wild
      seals form a different grouping inside the M. tuberculosis complex. This is the
      first time that tuberculosis has been detected in wild seals from the south
      western Atlantic coast.

PMID- 9025146
TI  - The historical background of the control of enzootic bovine leukosis in Estonia.
AB  - The authors describe the history of enzootic bovine leukosis (EBL) in Estonia,
      including the occurrence and distribution of disease within the cattle
      population, and the factors which have influenced disease spread since the 1950s.
      The principles of various control schemes which were applied from 1960 to 1994
      are also surveyed. Considerable progress in eradicating EBL has been achieved
      during recent years, as a result of systematic serological herd testing, and the
      slaughter of cattle infected with bovine leukaemia virus (BLV). The decrease in
      the numbers of EBL-affected cattle may be expressed by the reduction in the
      number of leukotic tumour cases recorded annually: from an average of 180 cases
      per 100,000 cows in the 1980s to four cases in 1994; and by the decrease in the
      average prevalence of BLV-infected animals in the cattle population, from 31.4%
      in 1989 to 0% in 1994. The national EBL control programme will be continued. It
      is hoped that Estonia can be declared EBL-free within the coming years.

PMID- 9025147
TI  - Prevalence of infectious bovine rhinotracheitis in southern India.
AB  - The authors describe a serological survey on the prevalence of infectious bovine
      rhinotracheitis (IBR) among cattle and buffalo (Bubalus bubalis) in three
      southern states of India. A local isolate of bovine herpesvirus 1 (BHV-1) from an
      outbreak of the respiratory form of IBR was used as a source of virus antigen in
      avidin-biotin enzyme-linked immunosorbent assay (ELISA). The overall prevalence
      of antibodies to BHV-1 in cattle was 50.9%, and in buffalo was 52.5%. Among
      breeding bulls, 114/120 samples from Tamil Nadu (95%) and 41/99 samples from
      Karnataka (41.4%) were seropositive. The possible association of IBR with bovine
      abortions was recorded in 31/56 samples (55.4%) from aborted crossbred cows.
      However, virus isolation was not performed on these animals. The authors also
      highlight the economic importance of IBR to the rapidly developing livestock
      industry in India.

PMID- 9025148
TI  - A new variant of the viral haemorrhagic disease of rabbits virus.
AB  - A new variant of viral haemorrhagic disease of rabbits (VHD) virus, recently
      detected in Poland and called Blaszki (BLA), gives positive results in enzyme
      linked immunosorbent assay (ELISA) and exhibits viral protein of 60 kilodaltons
      (VP 60), as detected by Western blot analysis. This BLA variant of VHD virus has
      caused high morbidity and mortality in rabbits, as have other reported variants
      with similar clinical signs and pathological lesions, but-in contrast to other
      variants-the BLA variant gave negative results in the haemagglutination test.
      This development indicates the limitations of haemagglutination testing in the
      diagnosis of VHD.

PMID- 9025149
TI  - Air streams and the introduction of animal diseases borne on Culicoides (Diptera,
      Ceratopogonidae) into Israel.
AB  - The role of air streams and climatic conditions in the transport of biting midges
      (Culicoides spp.), the vectors of bluetongue and Akabane viruses, is known from
      other parts of the world. Knowledge of such climatic systems may enable
      predictions to be made on the occurrence of these diseases and may also assist in
      drawing up vaccination and control programmes. In this study, data on
      temperature, relative humidity, wind speed and direction have been analysed for
      the years 1964, 1966, 1969 and 1988, at altitudes of 0.5 km, 1 km and 1.5 km. The
      authors examine the relationship between these parameters and outbreaks of
      bluetongue and Akabane. The results show that outbreaks of bluetongue and most
      seroconversions did not occur before the season of the Persian trough air-stream
      system. This was despite the fact that the vector C. imicola was present in March
      and April, i.e. before this air-stream system began. Circumstantial evidence to
      indicate the introduction of infected midges by wind is stronger than the
      evidence against such an introduction. In addition, the amount of precipitation
      in the spring seasons of 1968 to 1986 could not be positively correlated to the
      number of bluetongue outbreaks. These results indicate that cooperation among the
      countries in the region of the Persian trough air system could provide an early
      warning system against wind-borne infected vectors. An outbreak of bluetongue in
      one country would be a warning to the next country along this route.

PMID- 9025150
TI  - Epidemiology of inclusion body hepatitis in poultry in northern India from 1990
      to 1994.
AB  - The epidemiology of inclusion body hepatitis (IBH) was studied in poultry in
      northern India, from April 1990 to March 1994, to evaluate the various factors
      responsible for causing and determining the severity of the disease. Broiler
      chicks and Japanese quail (Coturnix coturnix japonica) were the species examined.
      The factor observed to be most commonly associated with IBH was the presence of
      aflatoxins in the feed at higher than permissible levels, i.e. 20 parts per
      billion. Avian adenovirus-1 was isolated from the livers of affected birds. In
      the final year of the study, a number of outbreaks of IBH caused heavy
      mortalities among three to five-week-old broiler chicks, which displayed typical
      IBH lesions in addition to hydropericardium.

PMID- 9025151
TI  - Cat-scratch disease and bacillary angiomatosis.
AB  - Cat-scratch disease (CSD) was first described by Debre in 1950, yet the causative
      bacterial agent of CSD remained obscure until 1992, when Bartonella (formerly
      Rochalimaea) henselae was implicated in CSD by serological and microbiological
      studies. B. henselae had initially been linked to bacillary angiomatosis (BA), a
      vascular proliferative disease most commonly associated with long-standing human
      immunodeficiency virus (HIV) infection or other significant immunosuppression. B.
      henselae has also been associated with bacillary peliosis, relapsing bacteraemia
      and endocarditis in humans. Cats are healthy carriers of B. henselae, and can be
      bacteraemic for months or years. It has recently been demonstrated that B.
      henselae can be transmitted from cat to cat by the cat flea, but not by direct
      contact between animals. The author discusses the present state of knowledge on
      the aetiology, clinical features and epidemiological characteristics of cat
      scratch disease and bacillary angiomatosis.

PMID- 9025152
TI  - Evaluation of the presence and risk of foot and mouth disease virus by commodity
      in international trade.
AB  - Potential sources of foot and mouth disease (FMD) virus include semen from bulls,
      rams, goats and boars; embryos and ova from ruminants and pigs; meat and meat
      products and milk and milk products. The author discusses precautions to prevent
      the transmission of FMD via these commodities.

PMID- 9025153
TI  - Bovine spongiform encephalopathy: an update.
AB  - A specialist group of the Office International des Epizooties met in May 1996 to
      prepare updated information on bovine spongiform encephalopathy (BSE): in
      particular on the development of the epidemic, geographical incidence, nature of
      the disease, transmission, precautions and control measures. A revised Chapter
      3.2.13. of the International Animal Health Code dealing with BSE, and an outline
      of the spongiform encephalopathies, are appended, along with a comprehensive
      bibliography.

PMID- 9025155
TI  - A perspective on equine viral arteritis (infectious arteritis of horses).

PMID- 9025154
TI  - An account on equine babesioses.

PMID- 9025156
TI  - Prologue: polycythemia vera. The closing of the Wasserman-Polycythemia Vera Study
      Group era.

PMID- 9025157
TI  - The very long-term evolution of polycythemia vera: an analysis of 318 patients
      initially treated by phlebotomy or 32P between 1969 and 1981.

PMID- 9025158
TI  - From efficacy to safety: a Polycythemia Vera Study group report on hydroxyurea in
      patients with polycythemia vera.

PMID- 9025159
TI  - Management of polycythemia vera with hydroxyurea.

PMID- 9025160
TI  - Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a
      final report on diagnostic criteria, survival, and leukemic transition by
      treatment.
AB  - This report suggests modest changes in the criteria used for the diagnosis of ET
      and allows tentative recommendations concerning therapy. As outlined in Table I,
      we believe that absent stainable marrow iron does not necessarily indicate iron
      deficiency in these patients and that the serum ferritin and RBC mean corpuscular
      volume should be incorporated in this assessment. Normal values speak strongly
      against iron-deficient erythropoiesis. A search for the bcr/abl gene
      rearrangement should be included with the marrow karyotype to exclude CML.
      Finally, cytogenetic data and morphologic study of the marrow should be used to
      be certain that a MDS should not be considered. It may be that measurements of
      serum thrombopoietin levels may be useful in the future. Nonetheless, in
      principle, ET remains a diagnosis of exclusion as we have originally suggested.
      For therapy, HU remains an excellent choice for the older patient at risk for
      thrombosis. Nonetheless, no myelosuppressive therapy remains a perfectly viable
      option, particularly for the young patient and the older with low thrombotic
      risk. The roles of anagrelide and alpha interferon in this setting have not been
      fully defined. Experience with both has still been relatively short. It would be
      ideal if prospective, randomized trials could be mounted to address these
      questions. We conclude with confidence that return to older approaches such as
      32P and AA in patients who fail on HU is to be discouraged. The use of anagrelide
      or interferon alfa seems to be a much more appropriate approach. We have not
      investigated the role of antithrombotic agents such as aspirin in ET. In PV, the
      combination of aspirin, 300 mg three times daily, and dipyridamole, 75 mg three
      times daily, failed to reduce the rate of thrombosis and was associated with an
      increased rate of hemorrhage. It is rational to suggest that lower doses of
      aspirin (ie, < 325 mg daily) might be associated with less hemorrhage and,
      perhaps, a beneficial effect on thrombosis. This remains to be shown.

PMID- 9025161
TI  - Interferon alfa: effects of long-term treatment for polycythemia vera.

PMID- 9025162
TI  - Anagrelide for control of thrombocythemia in polycythemia and other
      myeloproliferative disorders.

PMID- 9025163
TI  - FISHing among myeloproliferative disorders.

PMID- 9025164
TI  - In vitro erythropoiesis in polycythemia vera and other myeloproliferative
      disorders.
AB  - PV is a myeloproliferative disorder characterized by an elevated hematocrit and
      red blood cell mass. In vitro hematopoietic culture systems have been used
      extensively to characterize the cellular defect in PV. Erythroid progenitor cells
      from PV patients exhibit characteristic endogenous erythroid colony growth in
      serum-containing semisolid culture medium. These endogenous erythroid colonies
      can be used as a diagnostic tool to distinguish PV from other myeloproliferative
      disorders and secondary erythrocytosis. Both EPO independence and exquisite EPO
      sensitivity are mechanism which have been proposed to explain the growth of
      endogenous colonies. In contrast with normal erythroid progenitor cells which
      have both high and low affinity EPO-R, PV erythroid cells have only low affinity
      EPO-R, Molecular analyses did not reveal mutations in the PV EPO-R. These
      findings have failed to clarify the role of EPO in the etiology of PV. PV
      hematopoietic progenitor cells also exhibit increased sensitivity to the
      hematopoietic growth factors GM-CSF, IL-3, and SCF. As with EPO-R studies,
      examination of IL-3 and SCF receptors on PV erythroid cells has not identified
      mechanisms underlying the observed increased sensitivities to these hematopoietic
      growth factors. The recent development of a truly serum-free culture system has
      led to the observation that PV progenitor cells are more than 100-fold more
      sensitive to IGF-1 than are normal progenitor cells. In addition, the IGF-1
      receptor on PV progenitor cells exhibits increased basal phosphorylation and a
      hypersensitivity and hyperresponsiveness to IGF-1 with respect to tyrosine
      phosphorylation. Thus in PV, hypersensitivity to several hematopoietic growth
      factors may result in hyperproliferation of hematopoietic cells. This
      hypersensitivity ma be due to a defective intracellular mechanism common to these
      hematopoietic growth factors.

PMID- 9025165
TI  - Erythropoietin receptor mutations and human disease.

PMID- 9025166
TI  - Epilogue: broader lessons from the study of polycythemia vera.

PMID- 9025175
TI  - Bone cancer and limb-sparing surgery.

PMID- 9025176
TI  - Endoprosthetic replacement following limb-sparing resection for bone sarcoma.
AB  - Prosthetic replacements are widely used in the reconstruction of deficits created
      by surgical resection for bone sarcomas. The longevity, complications, and
      functional outcome of these reconstructions vary by anatomic location, prosthesis
      type, and mode of fixation. Distal femoral replacement appears to be the most
      reproducibly successful prosthetic reconstruction, particularly when utilizing a
      cemented rotating-hinge device. Expandable prostheses may be the only alternative
      to rotationplasty or ablation in the young skeletally immature patient. Aseptic
      loosening and bone resorption are frequently noted complications of prosthetic
      replacement for which successful revision is nearly always possible. The
      incidence of infection has been reduced by use of better soft tissue coverage.
      The concept of extracortical bone bridging continues to evolve while enhanced
      tendon attachment emerges as a new development.

PMID- 9025177
TI  - Allograft reconstructions.
AB  - Large fragment allografts provide a means of reconstructing an extremity after a
      major bone has been resected. The host has the ability to replace the
      transplanted bone with new bone, and it is at least theoretically possible that
      the allograft eventually will be totally removed and replaced by bone from the
      host. Retrieval studies suggest that although this does not happen, or happens
      very slowly, the transplanted bone is accepted by the host and heals to the host
      bone. The success rates are as good as those of other methods of reconstruction,
      although full recovery takes up to 1 year.

PMID- 9025179
TI  - Arthrodesis after resection of bone tumors.
AB  - Advances in chemotherapy and radiographic imaging have allowed resection and limb
      salvage surgery to be performed on the majority of patients with bone tumors.
      Extensive soft tissue resection, extra-articular resection, and social factors
      often contraindicate a mobile reconstruction of the involved or adjacent joint.
      In these cases, an arthrodesis often can maintain a functional extremity. Current
      soft tissue techniques and advances in orthopedic hardware have minimized
      complications and allowed successful outcomes for the majority of patients. This
      article reviews resection arthrodeses about the knee, shoulder, wrist, and ankle.
      The surgical technique, complications, and functional outcomes of these
      procedures are presented.

PMID- 9025178
TI  - Allograft prosthetic composite replacement for bone tumors.
AB  - Limb salvage for bone tumors has become the standard method of treatment. This
      technique involves removal of large segments of bone, most commonly around the
      hip and knee. Various types of reconstructive options are currently available,
      including osteoarticular allograft arthroplasty, modular oncology prosthetic
      arthroplasty, allograft prosthetic composite (APC) arthroplasty, and arthrodesis.
      Compared to other techniques, APC arthroplasty has many advantages, including
      restoration of bone stock, customization with conventional implant components,
      soft tissue attachment of tendons and ligaments, and preservation of the
      medullary canal of the host bone. The disadvantages of this technique include
      slow healing in the presence of chemotherapy, the possibility of disease
      transmission, and availability. The technique is suited either for aggressive
      benign tumors or for low-grade sarcomas where chemotherapy is not necessary.
      Further, it represents a good alternative for a failed modular oncology
      prosthesis, and also for the failed osteoarticular allograft because it restores
      bone stock. Good functional results have been reported with APC replacements, but
      long-term follow-up is needed to determine their durability.

PMID- 9025180
TI  - Rotationplasty.
AB  - Partial limb salvage by a rotationplasty procedure is possible in patients
      suffering from malignant tumors of the lower extremity. Upon diagnosis of a
      malignant tumor of the distal femur or proximal tibia, resection of the tumor is
      performed with wide margins, including the knee joint. The sciatic nerve is
      preserved, and the lower part of the leg is retransplanted to the thigh,
      observing a rotation of 180 degrees. This procedure results in a shortened leg
      with the ankle joint at the position of the former knee joint. The resulting
      stump is able to bear a prosthesis. The ankle rotated at 180 degrees serves as a
      substitute knee joint capable of moving a shank prosthesis, an ability which
      would have been lost with high amputation of the leg. The foot is able to carry
      load via the sole skin. There is no phantom pain. Experience with 40 cases is
      reported.

PMID- 9025181
TI  - Growing endoprostheses for primary malignant bone tumors.
AB  - Twenty years of experience with the use of growing endoprostheses for limb
      salvage in skeletally immature patients is reported. Alternatives for the
      management of primary malignant bone tumors in this group of patients are
      amputation, rotationplasty, and allograft or autograft reconstruction. The
      development of the currently used implant is charted, with commentary on the
      complications and difficulties which gave rise to design changes. Over this
      period, 123 expanding endoprostheses have been inserted in 108 patients in this
      institution, and the results of a series of 54 consecutive distal femoral
      replacements are reported. The mean functional score was 72%, and the local
      recurrence rate was 11%. The technique was successful in maintaining limb-length
      equality. We conclude that in specialized centers of orthopedic oncology that
      utilize an endoprosthesis with proven reliability of the expansion mechanism, the
      short- and long-term results of this technique justify its continued use.

PMID- 9025182
TI  - Malignant pelvic tumors: limb-sparing resection and reconstruction.
AB  - Limb salvage of malignant pelvic tumors should be considered when the tumor can
      be resected with a satisfactory surgical margin or when tumor location is such
      that amputation would not provide a better margin. Local recurrence rates
      approximate 17%, with higher recurrence rates in patients with positive
      microscopic resection margins. Skeletal reconstruction is not necessary following
      resection of the anterior pelvis or incomplete removal of the ilium because
      pelvic stability is maintained. In patients with resection of the ilium and loss
      of pelvic stability, iliosacral arthrodesis provides good function.
      Reconstruction following periacetabular resections remains extremely challenging.
      Options include iliofemoral arthrodesis or pseudarthrosis, massive allograft or
      autoclaved autograft with hip arthroplasty, and pelvic or saddle prosthesis. We
      favor iliofemoral arthrodesis in the young, active patient because it provides
      good function with a durable, stable limb.

PMID- 9025183
TI  - Special problems in limb-salvage surgery.
AB  - Limb-salvage surgery is a safe and effective treatment for malignancies of the
      musculoskeletal system. Careful evaluation and planning are necessary to avoid
      both early and late complications. Biopsy must be carefully performed to avoid
      unnecessary contamination and to obtain adequate tissue for an accurate
      diagnosis. Pathologic fractures present both a diagnostic and a therapeutic
      challenge, and evaluation strategies depend on the age of the patient. Treatment
      of a pathologic fracture depends on the location and the histology of the lesion
      and many host factors. Limb salvage may or may not be indicated. Instability is
      another problem with certain limb-salvage situations, e.g., when it is necessary
      to resect the scapula. Various approaches may obviate the problem. The salvage of
      failed limb-salvage procedures requires careful evaluation and planning. Patients
      with infections and local recurrences often require amputation surgery.
      Correctable problems following failed allograft reconstructions include collapse
      of the articular cartilage, joint instability, nonunion, and fracture of the
      allograft. Correctable problems following prosthetic arthroplasty include aseptic
      loosening, prosthetic fracture, and polyethylene wear. Approximately two thirds
      of patients with failed limb-salvage procedures will obtain a functional limb
      following revision surgery. Attention to these special problems may allow for
      greater success with limb-salvage surgery.

PMID- 9025184
TI  - Limb-sparing surgery for bone tumors: new developments.
AB  - The standard for local control of malignant bone tumors has been amputation.
      During the last decade, limb-sparing surgery has been common in the
      multidisciplinary management of bone sarcoma. Efforts continue toward improving
      local control of tumor while retaining the function of the reconstructed limb.
      Major challenges include defining adequate surgical margins and developing
      biologic and prosthetic reconstructions that match life expectancy. Our review
      highlights important refinements of earlier techniques, current innovations, and
      future directions in limb-salvage surgery.

PMID- 9025214
TI  - Spinal cord injuries: a shortened measure of function and mood.
AB  - A brief quality-of-life (QL) questionnaire was derived empirically from a cross
      sectional study of 98 SCI-patients (83% men, median age 33.5 years, and median
      time after injury 2.3 years). A comprehensive general battery of well-established
      questionnaires (Sickness Impact Profile (SIP), Mood Adjective Check List (MACL),
      and Hospital Anxiety and Depression (HAD) scale) was combined with a study
      specific set of questions to constitute patients' QL. A stepwise analysis model
      was used to define key areas and questions to be included in a brief SCI-adapted
      questionnaire. The central areas that independently mattered for SCI-patients'
      perception of good QL included mental health (no depressive feelings), physical
      and psychosocial dysfunction (no, or few and minor, limitations in mobility, body
      care and movement and social interaction), and SCI-related problems (no or little
      perceived difficulty with loss of independence due to injury). A 22-item
      questionnaire is suggested for routine clinical follow-up to assess more
      accurately when optimal treatment and services have been delivered.

PMID- 9025213
TI  - Long-term adaptation to electrically induced cycle training in severe spinal cord
      injured individuals.
AB  - Spinal cord injured (SCI) individuals most often contract their injury at a young
      age and are deemed to a life of more or less physical inactivity. In addition to
      the primary implications of the SCI, severe SCI individuals are stigmatized by
      conditions related to their physically inactive lifestyle. It is unknown if these
      inactivity related conditions are potentially reversible and the aim of the
      present study was, therefore, to examine the effect of exercise on SCI
      individuals. Ten such individuals (six with tetraplegia and four with paraplegia;
      age 27-45 years; time since injury 3-23 years) were exercise trained for 1 year
      using an electrically induced computerized feedback controlled cycle ergometer.
      They trained for up to three times a week (mean 2.3 times), 30 min on each
      occasion. The gluteal, hamstring and quadriceps muscles were stimulated via
      electrodes placed on the skin over their motor points. During the first training
      bouts, a substantial variation in performance was seen between the subjects. A
      majority of them were capable of performing 30 min of exercise in the first bout;
      however, two individuals were only able to perform a few minutes of exercise.
      After training for 1 year all of the subjects were able to perform 30 min of
      continuous training and the work output had increased from 4 +/- 1 (mean +/- SE)
      to 17 +/- 2 Kilo Joules per training bout (P < 0.05). The maximal oxygen uptake
      during electrically induced exercise increased from 1.20 +/- 0.08 litres per
      minute measured after a few weeks habituation to the exercise to 1.43 +/- 0.09
      litres per minute after training for 1 year (P < 0.05). Magnetic resonance cross
      sectional images of the thigh were performed to estimate muscle mass and an
      increase of 12% (mean, P < 0.05) was seen in response to 1 year of training. In
      biopsies taken before exercise various degrees of atrophy were observed in the
      individual muscle fibres, a phenomenon that was partially normalized in all
      subjects after training. The fibre type distribution in skeletal muscles is known
      to shift towards type IIB fibres (fast twitch, fast fatiguable, glycolytic
      fibres) within the first 2 years after the spinal cord injury. The muscle in the
      present investigation contained of 63% myosin heavy chain (MHC) isoform IIB, 33%
      MHC isoform IIA (fast twitch, fatigue resistant) and less than 5% MHC isoform I
      (slow twitch) before training. A shift towards more fatigue resistant contractile
      proteins was found after 1 year of training. The percentage of MHC isoform IIA
      increased to 61% of all contractile protein and a corresponding decrease to 32%
      was seen in the fast fatiguable MHC isoform IIB, whereas MHC isoform I only
      comprised 7% of the total amount of MHC. This shift was accompanied by a doubling
      of the enzymatic activity of citrate synthase, as an indicator of mitochondrial
      oxidative capacity. It is concluded that inactivity-associated changes in
      exercise performance capacity and skeletal muscle occurring in SCI individuals
      after injury are reversible, even up to over 20 years after the injury. It
      follows that electrically induced exercise training of the paralysed limbs is an
      effective rehabilitation tool that should be offered to SCI individuals in the
      future.

PMID- 9025215
TI  - The functional independence measure in spinal cord injured patients: comparison
      of questioning with observational rating.
AB  - Functional independence measure (FIM) is becoming widely used for all aspects of
      disabling diseases including spinal cord injury (SCI). It is recommended that it
      is rated by trained clinicians familiar with the patients. We aimed to compare
      the ratings of those patients who were questioned with those who were observed in
      a simulated environment. Fifty patients with SCI were included in the study. They
      were all FIM rated by the same clinician, first by questioning and then by
      observation. Although observational rating took much more time than questioning
      there was a very strong correlation between these two different rating methods.
      We can conclude that questioning SCI patients could be used as a valuable and
      quick way to assess the functional level of such patients. Although this does not
      exclude observational scoring that was generally higher and more motivational for
      the patient.

PMID- 9025217
TI  - Urinary tract dysfunction in multiple sclerosis: is there a relation with disease
      related parameters?
AB  - The lower urinary tract is affected by multiple sclerosis in many patients. We
      screened urologically and neurologically 120 patients with a confirmed diagnosis
      of multiple sclerosis. The mean age was 42 years (range 22 to 69 years).
      Urodynamic investigation as well as neuro-urophysiological investigations were
      performed in all patients. Renal ultrasound was used to study morphology, and
      excretory urogram (IVU) was used to assess renal function and the upper urinary
      tracts in 105 patients. Obstructive symptoms were found more commonly than
      irritative symptoms. The urinary symptoms were found to be related to disease
      duration and not to disability status. Urodynamic abnormalities were
      statistically significantly related to disease duration (X2 = 38.51; P = 0.0001),
      and to the disability status (X2 = 76.70; P = 0.0001). Few patients, only 3.3%,
      had upper urinary tract dilatation. With medical management, hydronephrosis
      disappeared in all of the patients and did not recur. A combination of oral
      pharmacological agents and clean intermittent catheterization was used in the
      majority of the patients. We conclude that lower urodynamic abnormalities can be
      present in every patient with multiple sclerosis, and appear to be related to
      disease duration and disability status, thus early treatment based upon
      urodynamic evaluation and close follow-up can reduce morbidity and improve the
      quality of life.

PMID- 9025216
TI  - Regulation of vasomotion of arterioles and capillaries in the cat spinal cord:
      role of alpha actin and endothelin-1.
AB  - Ring-shaped vasoconstrictions of arterioles at their branching sites have often
      been reported in vascular corrosion casts of the brain and spinal cord in rats
      and cats. It is surmised that smooth muscle cells in arteriolar walls could
      regulate the blood flow by changing the diameter of the lumen (ie vasomotion).
      However, few reports have described vasomotion at the capillary (capillaries have
      no smooth muscle cells). Also, there have been no reports on endothelin-1 in the
      arterioles and capillaries of the spinal cord. This study was designed to
      determine (1) the electron microscopic architecture of vasomotion; (2) the
      immunohistochemical identification of alpha actin and endothelin-1 in the
      arterioles and capillaries of the spinal cord. Twenty-seven adult mongrel cats
      were used to study vascular corrosion casts at the lumbosacral spinal cord
      segments immunohistologically and through scanning electron microscopic
      observations. Sections of the spinal cord were stained with monoclonal anti-alpha
      actin and endothelin-1 antibodies. Vascular corrosion casts demonstrated two
      types of vasomotion: a sausage-like peristalsis and a ring-shaped
      vasoconstriction at the arteriole and capillary levels. In the immunohistological
      study, alpha actin and endothelin-1 were identifiable in the vascular wall at the
      bifurcation, and pericytes were found to contain microfilaments of alpha actin.
      The ring-shaped vasoconstriction might be regulated by smooth muscle cells in
      arterioles and by pericytes in capillaries by releasing endothelin-1.

PMID- 9025218
TI  - Voiding dysfunction in patients with spinal cord lesions at the thoracolumbar
      vertebral junction.
AB  - Neurogenic voiding dysfunction invariably follows a complete spinal cord lesion.
      With spinal shock urodynamic investigation will show an areflexic bladder if the
      sacral spinal cord has been damaged, otherwise, if the lesion involves the
      suprasacral cord, an overactive bladder will result. There are some exceptions to
      this rule, particularly in those with lesions of the thoracolumbar vertebral
      junction, where the sacral cord is located, it may be difficult to predict
      urodynamic dysfunction merely on the basis of the vertebral body involved. 46
      patients with a complete SCI neurological lesion at the thoraco-lumbar vertebral
      junction underwent a neurourological evaluation including multi-channel
      urodynamic studies. Overall in 20 to 36% of the patients the urodynamic pattern
      was different from what one would have expected considering the anatomical level
      of the vertebral body involved. Urodynamic study is confirmed as an essential
      tool in the correct diagnostic and therapeutic approach to the voiding
      dysfunction in these type of patients.

PMID- 9025220
TI  - Static respiratory pressures in patients with post-traumatic tetraplegia.
AB  - The purpose of this study was to examine ventilatory muscle strength as
      represented by static respiratory pressures in 30 tetraplegic patients with a
      complete lesion between the fifth and the eighth cervical vertebrae. The
      Inspiratory/Expiratory Pressure Meter was used to obtain maximum static
      expiratory mouth pressure (PEmax) and maximum static inspiratory mouth pressure
      (PImax) measurements. The PEmax was measured at vital capacity and the PImax at
      residual volume. The measurements were effected while the patient was in the
      supported sitting position. The mean PEmax for the group was 50 cm H2O and the
      mean PImax was -65 cm H2O. There was a significant difference between the PEmax
      and PImax values. Unlike normal individuals most tetraplegic subjects in this
      study showed PImax values to be much higher than their PEmax values.

PMID- 9025219
TI  - The cost of ventilator-dependent spinal cord injuries-patients in the hospital
      and at home.
AB  - The number of ventilator-dependent SCI-patients is increasing steadily but also
      are the costs of adequate treatment in and outside hospital. Various technical
      aids for ventilation, mobility, nursing, and individual needs are available for a
      qualified life in the family, but the costs of these add up to $116.450. As
      phrenic nerve stimulators are very expensive, the cost for permanent ventilation
      cannot be reduced although diaphragmatic pacemakers have a real significant
      benefit for the patient's independence and quality of life. As the hospital
      charge is equal for all paraplegic, tetraplegic and ventilator-dependent patients
      including all medical and rehabilitative treatments, drugs and disposable
      materials, SCI-departments have a marked financial reduction of $481 daily
      compared with the amount of $1027 which has to be raised daily for the qualified
      care at home. This challenge can only be met by help from the community and from
      insurance companies and it is only then possible to provide these severely
      disabled patients with a good quality of life.

PMID- 9025221
TI  - The role of external sphincterotomy for patients with a spinal cord lesion.
AB  - For the last three decades external sphincterotomy has been well accepted as a
      treatment for bladder outlet obstruction in patients with a spinal cord lesions.
      Recently, however, its value has been brought into question. To assess the
      current place of this procedure in the treatment of the neuropathic bladder of
      spinal origin, we studied the outcomes of sphincterotomy in 32 patients. Post
      voiding residual urine volume decreased after surgery in 27 patients (84%),
      considerably in 22 (69%) of them. Clinical infection resolved in 14 out of 19
      patients (74%), hydronephrosis disappeared in two out of three (66%), and
      vesicourethral reflux improved in three out of five (60%) and was cured in two
      (40%). Six of the patients (19%) were freed from catheterization, but two
      patients (6%) lost partial continence. Sphincterotomy is an important tool in the
      treatment of spinal patients with bladder outlet obstruction and should be
      considered when the proper indications exist.

PMID- 9025222
TI  - Reinnervation of the rectum with a somatic nerve: a canine study.
AB  - The purpose of this communication was to evaluate the possibility of rectal
      stimulation through nerve autografting. Eleven mongrel dogs were studied. The
      abdomen was opened under anesthesia. The obturator nerve was cut at its entrance
      into the obturator foramen and was embedded in a tunnel within the musculature of
      the rectal wall. Six months later, the abdomen was re-opened and bilateral pelvic
      ganglionectomy was done to denervate the rectum. As the urinary bladder was also
      denervated subsequent to the pelvic ganglionectomy, cystostomy was performed. Two
      bipolar electrodes were applied to the obturator nerve. The effects of
      electrostimulation were evaluated under basic conditions after urecholine and
      atropine administration and after xylocaine topical application to the obturator
      nerve. After bilateral pelvic neurectomy, the basic rectal pressure dropped (P <
      0.05) and there was no response to urecholine or to atropine injection. Obturator
      nerve electrostimulation induced evoked potentials within the nerve as well as
      rectal pressure rise (P < 0.001); the former was abolished with xylocaine topical
      application to the nerve and the latter with atropine administration. Microscopic
      examination revealed that the Schwann cells and axons grew in the connective
      tissue between the rectal muscle bundles. In conclusion, reinnervation of the
      denervated rectum using a somatic nerve implant is possible. To our knowledge
      this study is the first to show "smooth' muscle excitability by stimulation of a
      somatic nerve implant.

PMID- 9025224
TI  - An adjustable table tennis bat and grip system for tetraplegics.
AB  - A table tennis bat and gripping system has been devised which can be used by
      people who are tetraplegic who are unable to hold the bat unassisted. The multi
      positional head of the bat allows the user to alter the bat angle with respect to
      the hand whilst an elasticated glove ensures the bat is held firmly in place
      allowing the player access to a greater range of playing shots. The system has
      been used successfully to introduce recently injured players to the game, and has
      also been used by a British ranked tetraplegic table tennis player. It is
      suitable for general, rehabilitative or competition use.

PMID- 9025223
TI  - Anaemia and serum protein alteration in patients with pressure ulcers.
AB  - The presence of anaemia and serum protein alteration frequently makes the
      treatment of pressure ulcers more difficult. Several haemato-chemical parameters
      were observed in 40 patients with sacral pressure ulcers in order to determine
      the pathogenesis of these complications. All of the patients showed mild-moderate
      anaemia with low serum iron and normal or increased ferritin and hypoproteinemia
      with hypoalbuminemia. Our results suggest that both anaemia and serum protein
      alteration depend on the chronic inflammatory state due to the presence of
      pressure ulcers. Both anaemia and hypoproteinemia disappeared after pressure
      ulcer healing. A correct diagnosis is important for the treatment. Iron therapy
      is useless and potentially dangerous (iatrogenic haemochromatosis) since anaemia
      is the result of the inability to use iron stores and not iron deficiency. The
      treatment of serum protein alterations should be based on a dietary therapy rich
      in protein and calories; the administration of albumin should be reduced, since
      albumin is low in essential amino-acids and too expensive; albumin administration
      should be limited to cases with severe hypoproteinemia and oedema.

PMID- 9025225
TI  - Scope and limitations of the manual assessment of muscle tone.

PMID- 9025226
TI  - Defining the editing 'reaction'.

PMID- 9025227
TI  - Resistance to HIV infection: the genes are only part of the solution.

PMID- 9025228
TI  - Unraveling the mysteries of streptococci and their relations with the host.

PMID- 9025230
TI  - Vaccination in pulses: a strategy for global eradication of measles and polio?
AB  - Recent American successes against poliomyelitis and measles have been attributed
      to repeated 'pulse' vaccination campaigns. Whilst logistic and economic
      constraints will be crucial, a deeper epidemiological understanding of the
      mechanism, strengths and weaknesses of pulse vaccination will optimize the
      chances of success elsewhere in the world.

PMID- 9025229
TI  - Murine coronavirus infection: a paradigm for virus-induced demyelinating disease.
AB  - A variety of neurological diseases in humans, including multiple sclerosis (MS),
      have been postulated to have a viral etiology. The use of animal models provides
      insights into potential mechanism(s) involved in the disease process. The murine
      coronavirus-induced demyelinating disease in rodents is one such model for
      demyelinating disease in humans.

PMID- 9025231
TI  - In search of virulence factors of human bacterial disease.
AB  - Traditional genetic techniques and a variety of animal and tissue-culture model
      systems have sustained the study of bacterial virulence mechanisms for several
      decades. However, the recent application of newly developed molecular and
      cellular techniques has brought our understanding of bacterial pathogenesis to
      new heights by permitting the identification and analysis of previously unknown
      constitutively and differentially expressed virulence-associated factors.

PMID- 9025232
TI  - Probing the dynamics of prion diseases with amphotericin B.
AB  - Amphotericin B (AmB) is one of the rare drugs that affect the course of
      experimental prion diseases and modify the kinetics of abnormal prion protein
      accumulation in the central nervous system. Therefore, AmB could be used as a
      pharmacological tool to contribute to our understanding of the pathogenic
      mechanisms involved in these neurodegenerative disorders.

PMID- 9025233
TI  - Virulence and transmissibility of pathogens: what is the relationship?
AB  - The fitness of most pathogenic microorganisms depends on transmission from host
      to host. This requires adaptation for dissemination, translocation and survival
      between hosts, as well as for colonization. A complex relationship exists between
      these components of microbial fitness and virulence. Understanding this
      relationship has important implications for research and public health.

PMID- 9025234
TI  - The bacterial outer membrane as a drug barrier.
AB  - The outer membranes of Gram-negative bacteria constitute a semi-permeable
      barrier, as indicated by the corresponding alterations in outer membrane
      permeability and in antibiotic susceptibility resulting from mutation or
      polycation action. Restricted outer membrane permeability works in synergy with
      co-determinant resistance mechanisms, such as the periplasmic enzyme beta
      lactamase or active efflux mechanisms, bringing about antibiotic resistance.

PMID- 9025253
TI  - Synthesis and pharmacology of the enantiomers of UH301: opposing interactions
      with 5-HT1A receptors.
AB  - The (S)-enantiomer of 5-fluoro-8-hydroxy-2-(dipropylamino) tetralin [(S)-2a; (S)
      UH301] was the first reported 5-HT1A receptor antagonist. We now give a full
      account on the synthetic effort leading to the preparation of the racemate and
      the enantiomers of 2a. The crystal and molecular structure of 2a. HBr has been
      determined by X-ray diffraction and the absolute configuration has been deduced
      using statistical tests of the crystallographic R values. The unit cell is
      tetragonal (P4(1)2(1)2) with a = b = 13.2235(2), c = 39.560(1) A and contains two
      crystallographically independent molecules in each asymmetric unit. The two solid
      state conformers differ in the conformation of the N-propyl groups. The
      pharmacological characterization of the enantiomers was done by use of in vivo
      biochemical and behavioural assays in rats. The (R)-enantiomer of 2a is a 5-HT1A
      receptor agonist of low potency while (S)-2a does not exhibit any agonist
      properties at 5-HT1A receptors. As a consequence of the opposing effects of the
      enantiomers, the racemate, rac-2a, does not produce any clear-cut effects in
      rats. The reduced efficacy of (S)-2a as compared to the well known 5-HT1A
      receptor agonist 8-hydroxy-2-(dipropylamino) tetralin (1;8-OH-DPAT) may be due to
      the fluoro-substituent induced negative potential of the aromatic ring.

PMID- 9025254
TI  - Synthesis and analysis of the enantiomers of calmidazolium, and a 1H NMR
      demonstration of a chiral interaction with calmodulin.
AB  - Calmidazolium [R24571, 1-[bis(4-chlorophenyl)methyl]-3-[2-(2,4-dichlorophenyl)-2
      [(2,4- dichlorophenyl)methoxy]ethyl]-1H-imidazolium chloride] is a potent
      calmodulin inhibitor. This paper describes the synthesis and properties of the
      enantiomers of calmidazolium from the enantiomers of miconazole [1(N)-(2-(2,4
      dichlorobenzyloxy)-2-(2,4 dichlorophenyl))-ethyl imidazole], prepared from the
      racemate by chiral preparative scale high performance liquid chromatography.
      Overlap between ligand and protein resonances in the aromatic region of the 1H
      NMR spectrum of the calmidazolium-calmodulin complexes has been obviated by
      preparation of the protein with all of its nine phenylalanine rings deuterated
      (Phe-d5 calmodulin). This has been accomplished by the overexpression of
      calmodulin derived from Trypanosoma brucei rhodiesiense in E. coli in a medium
      supplemented with ring-deuterated phenylalanine. The kinetics of binding of each
      enantiomer are slow on the 1H NMR time scale as judged by the behaviour of the H2
      resonance of Histidine-107, which is clearly visible under the sample conditions
      used. The aromatic spectral regions of the protein-bound (+) and (-) enantiomers
      contrast strikingly, reflecting differences in bound environment and/or
      conformation.

PMID- 9025255
TI  - Substituent effects on the enantioselective retention of anti-HIV 5-aryl-delta 2
      1,2,4-oxadiazolines on R,R-DACH-DNB chiral stationary phase.
AB  - A series of racemic 3-phenyl-4-(1-adamantyl)-5-X-phenyl- delta 2-1,2,4-oxadiazo
      lines (PAdOx) were directly resolved by HPLC using a Pirkle-type stationary phase
      containing N,N'-(3,5-dinitrobenzoyl)-1(R),2(R)-diaminocyclohexane as chiral
      selector. The more retained enantiomers have S configuration, as demonstrated by
      X-ray crystallography and circular dichroism measurements. The influence of
      aromatic ring substituents on enantioselective retention was quantitatively
      assessed by traditional linear free energy-related (LFER) equations and
      comparative molecular field analysis (CoMFA). In good agreement with previous
      findings, the results from this study indicate that the increase in retention
      (k') is favoured mainly by the phi-basicity and the hydrophilicity of solute,
      whereas enantioselectivity (alpha) can be satisfactorily modeled by electronic
      and bulk parameters or CoMFA descriptors. The LFER equations and CoMFA models
      gave helpful insights into chiral recognition mechanisms.

PMID- 9025256
TI  - Steric aspects of formoterol and terbutaline: is there an adverse effect of the
      distomer on airway smooth muscle function?
AB  - Experiments were made on isolated tissues from guinea-pig to test the hypothesis
      that the distomers of rac-beta 2-adrenoceptor agonists induce airway
      hyperreactivity. Tracheal strip preparations were contracted with carbachol. Both
      rac- and (R;R)-formoterol (2 and 1 mumol/l, respectively) produced an immediate
      relaxation, followed by a slow recovery of tone. (S;S)-Formoterol (2 mumol/l) had
      no effect on smooth muscle tone. Similar results were obtained with the
      enantiomers of terbutaline. In other strip preparations of the trachea or the
      main bronchi, cholinergic or nonadrenergic/noncholinergic (NANC) excitatory
      responses were evoked by electrical field-stimulation. The eutomers, (R;R)
      formoterol and (R)-terbutaline, inhibited concentration-dependently both
      cholinergic and NANC-induced contractions. The distomers, (S;S)-formoterol and
      (S)-terbutaline, showed qualitatively the same effects but were about 1,000 times
      less potent than the corresponding eutomer. In a third series of experiments,
      either enantiomer of formoterol was administered to an electrically stimulated
      vagus nerve-trachea tube preparation. The nerve-induced contractions were
      inhibited by both enantiomers, but (S;S)-formoterol was about 1,000 times less
      potent than (R;R)-formoterol. For both enantiomers of formoterol, about tenfold
      higher concentrations was required to obtain the same degree of inhibition when
      given intratracheally as compared with administration in the external medium.
      There was no indication in any of the experimental approaches that (S;S)
      formoterol or (S)-terbutaline might enhance the response to cholinergic or NANC
      related stimuli.

PMID- 9025257
TI  - Chiral synthesis and pharmacological evaluation of the enantiomers of SM32, a new
      analgesic and cognition-enhancing agent.
AB  - The enantiomers of 3-alpha-tropyl 2-(phenylthio)butyrate (SM32, 1) were prepared
      by chiral synthesis and tested for analgesic, cognition-enhancing, and ACh
      releasing properties. They show enantioselectivity in some of the tests, the
      eutomer being related in configuration to R-(+)-hyoscyamine.

PMID- 9025259
TI  - Direct purification of lysozyme using continuous counter-current expanded bed
      adsorption.
AB  - We describe the application of a novel technique for the continuous counter
      current chromatography of proteins. The unit operation has shown potential in
      extracting targeted species from unclarified feedstocks, delivering clarified
      streams of purified product. The adsorbent used in this equipment consists of a
      perfluorocarbon matrix, coated with poly(vinyl alcohol), and derivatized with the
      triazine dye Procion Red HE-7B. Purification of lysozyme from egg-whites and
      enriched bovine milk could be carried out continuously. The former was extracted
      in 90.5% yield at a rate of 7400 U/min, achieving a purification factor of 19.4.
      Lysozyme from the enriched milk sample was extracted continuously at a rate of
      41000 U/min, in 66.0% yield. The continuous products streams in both cases were
      fully clarified, thus enabling their direct application to a final polishing
      step, if desired.

PMID- 9025258
TI  - A QSAR study of the antimalarial activity of some synthetic 1,2,4-trioxanes.
AB  - The antimalarial activity of a series of synthetic 1,2,4-trioxanes is correlated
      with molecular structure by using a pharmacophore search method (CATALYST). The
      technique is shown to have predictive accuracy and confirms that docking between
      an active trioxane and the receptor, heme, is the crucial step for drug action.

PMID- 9025260
TI  - Determination of staphylococcal enterotoxin B by on-line (micro) liquid
      chromatography-electrospray mass spectrometry.
AB  - The use of (micro) liquid chromatography electrospray mass spectrometry (LC-ES
      MS) was investigated as potential technique for the determination of the high
      molecular-mass protein toxin Staphylococcal Enterotoxin B (SEB). The molecular
      mass was determined (28,366.3 +/- 1.1) by flow injection analysis and micro-LC-MS
      with a TSK-gel Phenyl-5PW column packing. Both methods allowed molecular-mass
      determination of SEB at levels down to 3 pmol/ml. Additional evidence of
      identification was obtained by detecting the presence of a disulfide bridge by
      the addition of 2-mercaptoethanol and by tryptic digestion. Collision induced
      dissociation spectra were recorded from the major tryptic fragments resulting in
      a sufficient number of sequence ions to allow for the determination of the amino
      acid sequence. On the analysis of the tryptic digests with C18 reversed-phase
      columns the use of micro-LC-MS-MS resulted in an 30-40-fold increase in
      sensitivity as compared with conventional-size LC-MS-MS.

PMID- 9025261
TI  - Isocratic non-aqueous reversed-phase high-performance liquid chromatographic
      separation of capsanthin and capsorubin in red peppers (Capsicum annuum L.),
      paprika and oleoresin.
AB  - A simple, rapid high-performance liquid chromatography method has been devised in
      order to separate and quantify the xanthophylls capsorubin and capasanthin
      present in red pepper (Capsicum annuum L.) fruits and preparations made from them
      (paprika and oleoresin). A reversed-phase isocratic non-aqueous system allows the
      separation of xanthophylls within a few minutes, with detection at 450 nm, using
      methyl red as internal standard to locate the various carotenoids and
      xanthophylls found in plant extracts. The selection of extraction solvents, mild
      saponification conditions, and chromatographic features is evaluated and
      discussed. The method is proposed for rapid screening of large plant populations,
      plant selection, as well as for paprika products and oleoresin, and also for
      nutrition and quality control studies.

PMID- 9025262
TI  - Approach to the thermodynamics of enantiomer separation by gas chromatography.
      Enantioselectivity between the chiral inhalation anesthetics enflurane,
      isoflurane and desflurane and a diluted gamma-cyclodextrin derivative.
AB  - The thermodynamics of enantioselectivity, -delta D,L(delta G), -delta D,L(delta
      H), delta D,L(delta S) and Tiso, have been determined by gas chromatography
      employing the concept of the retention increment R' for the inhalation
      anesthetics enflurane (1), isoflurane (2) and desflurane (3) and the selector
      octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-gamma-cyclodextrin (4) in the
      polysiloxane SE-54. It is shown that the separation factor alpha is concentration
      dependent. Therefore, the separation factor alpha should not be employed as a
      criterion for enantioselectivity in diluted systems. The -delta DL(delta G) data
      for 1 and 4 are corroborated by 1H NMR spectroscopic measurements.

PMID- 9025263
TI  - Capillary zone electrophoresis of oligosaccharides derivatized with N-(4
      aminobenzoyl)-L-glutamic acid for ultraviolet absorbance detection.
AB  - A charged and strongly UV-absorbing tag, N-(4-aminobenzoyl)-L-glutamic acid)
      (ABG), was coupled to oligosaccharides by reductive amination under mild
      conditions. The effectiveness of ABG as a derivatization agent is shown through
      the separation of isomaltooligosaccharides from a dextran hydrolysate. The
      minimum detectable quantities in the subpicomole range are demonstrated.

PMID- 9025264
TI  - Development of a high-performance capillary isoelectric focusing technique with
      application to studies of microheterogeneity in chicken conalbumin.
AB  - A robust, simple, reproducible isoelectric focusing method using capillary
      electrophoresis that exhibits high stability, migration time reproducibility and
      pH linearity over a wide pH gradient was developed. Consecutive runs (over 113
      runs) of several proteins and one peptide with isoelectric points (p/s) ranging
      from 9.45 to 2.75 yielded excellent migration time reproducibility (< 2% R.S.D.).
      Experimental parameters including buffer aging and capillary-to-capillary
      variation were thoroughly examined and optimized to improve the migration time
      reproducibility. The capillary isoelectric focusing (CIEF) method was applied to
      the analysis of chicken conalbumin (ovotransferrin), an iron-binding protein in
      egg white. Conalbumin (low iron content) separated into three major components
      with p/s of 7.2, 6.6 and 6.2. When the protein was saturated with iron (2
      Fe/mol), a shift to lower p/s was detected. Chicken serum transferrin subjected
      to CIEF gave a pattern similar to conalbumin with three p/s of 7.1, 6.6 and 6.1,
      indicating that it was not fully saturated with iron. Thus, CIEF can be used as a
      potential analytical method to provide information about the metal-binding
      properties of specific metalloproteins.

PMID- 9025265
TI  - Trace determination of iron in water at the microgram/l level by on-line coupling
      of capillary isotachophoresis and capillary zone electrophoresis with UV
      detection of the EDTA-Fe (III) complex.
AB  - The determination of iron in water at the trace level by on-line coupled
      capillary isotachophoresis and capillary zone electrophoresis (CITP-CZE) with a
      commercial column coupling device is described. Iron is determined as the
      negatively charged complex with EDTA which is highly UV-absorbing and thus
      enables photometric detection at 254 nm. The analyses are performed using 10
      mmol/l HCl + 20 mmol/l L-histidine + 0.1% hydroxypropylmethyl cellulose (pH 6.0),
      5 mmol/l MES, and 25 mmol/l MES + 10 mmol/l bis-tris-propane (pH 6.6) which
      served as leading, terminating and background electrolyte, respectively. Samples
      are acidified with HNO3, diluted and EDTA added (to a final concentration of 10(
      4) mol/l) prior to CITP-CZE analysis. The detection limit of Fe(III) is 10
      micrograms/l, and is given by the chemical noise due to the impurities of the
      chemicals used enriched by the ITP preconcentration step. The precision of the CE
      measurement, expressed by the relative standard deviation, is about 3% (at the
      400 micrograms/l level); the recovery is between 80 and 115% depending on the
      iron concentration level (40-400 micrograms/l).

PMID- 9025266
TI  - Quantitative evaluation of carbon isotopic fractionation during reversed-phase
      high-performance liquid chromatography.
AB  - The fractionation of 13C during low-performance preparative LC and high
      performance LC is reported quantitatively for methyl palmitate and using high
      precision isotope ratio mass spectrometry (IR-MS). For both preparative and high
      performance analytical columns, 13C enrichment is about 7% greater than the
      parent starting material, drops sharply in the first section of the peak and then
      settles to a value about 1% below that of the starting material. Recycling over a
      single HPLC column did not induce greater fractionation. These results emphasize
      the importance of quantitative peak collection for high-precision IR-MS studies,
      particularly the first part of the peak where the isotope ratio changes rapidly.

PMID- 9025267
TI  - Degradation of pentachlorophenol in soil by Streptomyces rochei 303.
AB  - The fate of pentachlorophenol (PCP) in soil under natural conditions was
      investigated. It was revealed that the total amount of PCP significantly
      decreased when soil was inoculated by Streptomyces rochei 303, a strain
      destructor of chlorophenols. The products of PCP transformation, such as tetra-
      and trichlorophenols, pentachlorobenzene, chlorinated dioxins, were identified
      after the first month of the experiment. Their quantity was less in the variant
      with the introduced strain compared to control.

PMID- 9025268
TI  - Use of residence time distribution for evaluation of gaseous pollutant
      volatilization from stored swine manure.
AB  - A quantification analysis for evaluation of gaseous pollutant volatilization as a
      result of mass transfer from stored swine manure is presented from the viewpoint
      of residence time distribution. The method is based on evaluating the moments of
      concentration vs. time curves of both air and gaseous pollutants. The concept of
      moments of concentration histories is applicable to characterize the dispersal of
      the supplied air or gaseous pollutant in a ventilated system. The mean age or
      residence time of airflow can be calculated from an inverse system state matrix
      [B]-1 of a linear dynamic equation describing the dynamics of gaseous pollutant
      in a ventilated airspace. The sum elements in an arbitrary row i in matrix [B]-1
      is equal to the mean age of airflow in airspace i. The mean age of gaseous
      pollutant in airspace i can be obtained from the area under the concentration
      profile divided by the equilibrium concentration reading in that space caused by
      gaseous pollutant sources. Matrix [B]-1 can also be represented in terms of the
      inverse local airflow rate matrix ([W]-1), transition probability matrix ([P]),
      and air volume matrix ([V]) as, [B]-1 = [W]-1[P][V]. Finally the mean age of
      airflow in a ventilated airspace can be interpreted by the physical
      characteristics of matrices [W] and [P]. The practical use of the concepts is
      also applied in a typical pig unit.

PMID- 9025269
TI  - Copper depletion/repletion of human ceruloplasmin is followed by the changes in
      its spectral features and functional properties.
AB  - Copper ions of different types were gradually eliminated from ceruloplasmin (CP1;
      ferro-O2-oxidoreductase, EC 1.16.3.1.) by dialyzing the enzyme against KCN.
      Protein was sampled 2, 4, 6, 22, and 28 h after the dialysis started. Atomic
      absorption allowed us to estimate the amount of copper atoms per CP molecule.
      Light absorption in the UV and visible regions along with fluorescence and EPR
      spectra were also registered. Oxidase and dismutase activities of the enzyme were
      measured at each step. The combination of the data thus obtained allowed us to
      trace the sequence of CP depletion of certain copper ions. The same methods were
      applied in reconstitution studies to detect the return of different types of
      Cu2+. The experiments were performed on CP samples differing in the amount of
      copper still bound after CN- treatment. It is shown that the oxidase activity is
      efficiently brought back to CP if, after the dialysis against cyanide, the
      catalytic center had preserved its type 3 Cu2+. Dismutase activity of CP did not
      depend greatly on the presence or absence of type 1 and type 2 copper ions. The
      results obtained allow a more precise evaluation of the role of different types
      Cu2+ in the assembly of the complex catalytic center of CP and in the
      accomplishment by the enzyme of its multiple functions.

PMID- 9025270
TI  - Structural and biological aspects of copper (II) complexes with 2-methyl-3-amino
      (3H)-quinazolin-4-one.
AB  - A series of new copper (II) complexes with 2-methyl-3-amino(3H)-quinazolin-4-one
      (MAQ) and various anions (Cl-, Br-, ClO(-)4, NO(-)3, SCN-, and SO(2-)4 was
      prepared. Their structures and properties were characterized by elemental
      analysis, IR, UV-Vis and ESR spectroscopy, molar conductivity, and magnetic
      moment measurements. The square-planar complex was only obtained in the presence
      of perchlorate anion, whereas the five coordinate species, which have a square
      pyramidal structure, were obtained for chloro and bromo complexes. In the case of
      hexa coordinate complexes, in which nitrate, sulphate, or thiocyanate is attached
      to a copper(II) ion in a 1:2 (metal:ligand) ratio, a distorted octahedral
      geometry around copper(II) is proposed. The antimicrobial activity of the free
      ligand and its copper(II) complexes clearly illustrates that the compounds have
      both an antibacterial and antifungal potency against the organisms tested. In
      most cases, the complexes were found to be more active than the free ligand, but
      in some cases, an equal activity was displayed. To further elucidate the
      biological activity of the complexes, their activities towards active oxygen
      species, such as H2O2 and O(-)2, were investigated. A probable mechanism for the
      cytotoxic reaction with the different organisms is proposed.

PMID- 9025271
TI  - Kinetic analysis of the cis-diamminedichloroplatinum(II)--cysteine reaction:
      implications to the extent of platinum--DNA binding.
AB  - The reaction between cis-diamminedichloroplatinum(II) (cis-DDP) and L-cysteine
      was examined at neutral pH at 37 degrees C. The reaction proceeds through a
      Pt(NH3)2 (cys)Cl intermediate which undergoes parallel reactions with a second
      molecule of cysteine to form a bis(cysteine) complex, Pt(NH3)2(cys)2 and with the
      starting platinum complex to form a cysteine-bridged dinuclear complex. In the
      presence of excess cysteine, the product is predominantly the bis(cysteine)
      complex. The intermediate is formed by the direct reaction of the platinum
      complex with cysteine with a bimolecular rate constant 2.2 +/- 0.2 x 10(-2) M-1.s
      1 at 37 degrees C as well as through a rapid reaction with the mono aqua-platinum
      complex. The rate constant for the formation of the dimer was evaluated to be
      0.24 +/- 0.4 M-1.s-1, an order of magnitude higher than that for the mononuclear
      complex formation. The intermediate reacts with a second cysteine molecule with a
      bimolecular rate constant, 5.6 +/- 0.4 x 10(-2) M-1.s-1. The rate constant for
      the equation of Pt(NH3)2(cys)Cl was evaluated to be 1.8 +/- 0.2 10(-4) s-1. The
      Pt-195 chemical shifts for the mono(cysteine), bis(cysteine), and cysteine
      bridged dimer were found to be -3308, -3705, and -3104 ppm. The bis(cysteine)
      complex at neutral pH undergoes slow reaction (t1/2 approximately equal to four
      days) to form a secondary product, presumably Pt(NH3)(cys)2, in which one
      cysteine acts a bidentate chelating agent. In acidic solution, with equimolar
      concentrations of cysteine and diaqua-platinum complex, the reaction
      predominantly yielded a cysteine bridged dimeric complex. When cysteine
      concentration was increased fourfold over the platinum complex, the bis(cysteine)
      chelate with complete removal of coordinated ammonia appeared as the dominant
      product. The platinum-195 chemical shift for this chelate was found to be -3290
      ppm. Considering the abundance of thiols in amino acids/peptides and replication
      enzymes in the cellular milieu, it remains to be seen how platinum complexes
      react with DNA. Direct platination to replication enzymes as a possible mechanism
      for antineoplactic activity is yet to be ruled out.

PMID- 9025272
TI  - The crystal and molecular structure of (HgL2)n (L = 4,6-dimethylpyrimidine-2
      thiolate)--an unusual helical supramolecular assembly in solid phase: in search
      of a new antidote to mercury poisoning.
AB  - An X-ray crystallographic study reveals that in solid phase, 4,6
      dimethylpyrimidine-2-thiol (4,6Me2 Pm2SH) forms a multinuclear complex with
      mercury, containing an open HgN3S2 core and exhibiting a helix-like
      polymerization through repetitive distant Hg(sp3d) ... N(sp2) interactions along
      the b axis of the lattice. The complex, therefore, exemplifies a supramolecular
      assembly, generated by successive vacant ligand site promoted self-associations.
      It crystallizes in the monoclinic space group P2(1)/c, a = 11.808(2), b =
      9.198(2), and c = 14.702(3) A, beta = 112.19(3)0, Z = 4 (monomers). Such self
      associative distant interactions are absent in solution phase, as observed from
      the 1H NMR spectrum (acetone-d6, TMS). A preliminary toxicological study of the
      pyrimidinethiol ligand reveals a high toxicity at substantially higher doses and
      appreciably low toxic effects at lower doses. The ligand is also highly potent in
      inhibiting all common gram negative bacteria (except the acid fast group, which
      was not tested) and this property may endow it with some side therapeutic uses
      when considered as an antidote to mercury poisoning following some functional
      modifications in order to reduce the toxic effects, even when administered at
      higher doses.

PMID- 9025273
TI  - Characterization of zinc-substituted cytochrome c by circular dichroism and
      resonance Raman spectroscopic methods.
AB  - Iron(III) in cytochrome c is replaced with zinc(II) by a modification of a method
      published by others, and the procedure is described in full detail. Three forms
      of cytochrome c-those containing iron(III), iron(II), and zinc(II)-are examined
      by circular dichroism spectroscopy and resonance Raman spectroscopy. Spectra of
      both kinds show that introduction of zinc(II) ions does not appreciably alter the
      overall structure and conformation of cytochrome c. Resonance Raman spectra
      indicate the size of the porphyrin "core" that is inconsistent with six
      coordination and consistent with five-coordination. Unlike the iron(III) and
      iron(II) ions, which are bound to two axial ligands (His 18 and Met 80), the
      zinc(II) ion in cytochrome c seems to be bound to only one, most probably His 18.
      Evidence pertaining to the question of axial coordination is discussed.

PMID- 9025274
TI  - Pathogenesis of enteric infection by Campylobacter.

PMID- 9025275
TI  - Colonial opacity variations among the choleragenic vibrios.
AB  - Cultures of Vibrio cholerae 01, biotype El Tor, from the current epidemic of
      cholera in the Western Hemisphere, and of the new V. cholerae serogroup O139,
      from the current outbreak in India and Bangladesh, revealed marked colonial
      heterogeneity when received by the authors. By comparison with reference colony
      types, using a stereoscope and transmitted oblique illumination, colonies of
      approximately 10 different degrees of opacity could be distinguished. In
      contrast, strains freshly isolated from patients and rapidly and carefully
      preserved were more homogeneous although still differentiable by this technique.
      These (and older) observations prompted the questions: (1) why is a V. cholerae
      colony opaque or translucent? and (2) what benefit is it to the vibrios to vary
      their colonial appearance? The observed changes in colonial opacity, which are
      reversible, are sometimes (rarely) accompanied by changes in virulence for infant
      rabbits and, more frequently, by other phenotypic variations including the
      ability to produce poly-beta-hydroxybutyrate inclusion bodies on glycerol
      containing medium, the degree of encapsulation in 0139, changes in outer-membrane
      proteins, alteration in lipopolysaccharide structure, changes in expression of
      glycolytic pathways, and differences in ability to survive under adverse
      conditions. Colonial variations in choleragenic vibrios are phenotypically
      multifactorial. The genetic mechanisms(s) underlying the observed phenotypic
      changes remain to be defined.

PMID- 9025276
TI  - Use of siderophores to type pseudomonads: the three Pseudomonas aeruginosa
      pyoverdine systems.
AB  - Eighty-eight Pseudomonas aeruginosa isolates, most of them from the Collection of
      Bacterial Strains of the Institut Pasteur, Paris, were analysed for their
      pyoverdine-mediated iron incorporation system by different methods, including
      pyoverdine isoelectrofocusing analysis, pyoverdine-mediated growth stimulation,
      immunoblot detection of (ferri)pyoverdine outer-membrane receptor and pyoverdine
      facilitated iron uptake. The same grouping of the strains was reached by each of
      these methods, resulting in the classification of the P. aeruginosa isolates,
      even those which were devoid of pyoverdine production, into three different
      siderophore types. Forty-two percent of the strains were identified with the type
      strain P. aeruginosa ATCC 15,692 (group I), 42% were identical with the second
      type-strain P. aeruginosa ATCC 27,853 (group II) and 16% reacted identically with
      the clinical isolate P. aeruginosa Pa6, whose pyoverdine was recognized in this
      study to be identical in structure to the pyoverdine produced by a natural
      isolate, P. aeruginosa strain R. No new pyoverdine species was detected among
      these strains.

PMID- 9025277
TI  - TNF-alpha, IL-1 alpha, IL-6 and ICAM-1 expression in human keratinocytes
      stimulated in vitro with Escherichia coli heat-shock proteins.
AB  - Bacterial heat-shock proteins (HSPs) from Escherichia coli (GroES, GroEL and
      DnaK) were studied for their ability to induce by themselves the expression and
      release of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1
      alpha), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) by
      cultured human keratinocytes. The surface expression of ICAM-1 was also
      investigated. In the supernatants of untreated cells none or a minimal amount of
      these molecules was found. After 48 h of stimulation with GroEL significant
      amounts of TNF-alpha, IL-1 alpha, IL-6 and soluble ICAM-1 were detected, reaching
      maximum concentrations at 1 microgram ml-1. The same effect was elicited by DnaK
      but to a lesser extent. Treatment of keratinocytes with GroEL and DnaK also
      increased TNF-alpha, IL-1 alpha, IL-6 and ICAM-1 mRNA levels. GroES showed
      significant activity only on the expression and release of IL-6. GroEL and DnaK
      were also able to up-regulate the surface expression of ICAM-1 on keratinocytes.
      The effects on ICAM-1 expression seemed to be directly due to HSPs and not
      mediated via cytokines. Furthermore, these effects were due to the properties of
      HSPs because they were inhibited by specific monoclonal antibodies. These
      findings support the potential role of HSPs in modulating cell interactions
      during immunological and inflammatory responses in the skin.

PMID- 9025278
TI  - Monoclonal antibodies against Streptococcus pneumoniae detect epitopes on
      eubacterial ribosomal proteins L7/L12 and on streptococcal elongation factor Ts.
AB  - Two monoclonal antibodies (mAbs) designated 144,H-3 (IgG2a) and 218,C-5 (IgM)
      were produced after immunization of mice with two different heat-treated and
      sonicated pneumococcal strains. Western blotting, with solubilized proteins from
      different bacterial genera and from mammalian lymphocytes, showed that both mAbs
      reacted with a protein of approximately 12 kDa in all 66 strains of eubacteria
      examined, representing 27 different species. The 12 kDa protein was isolated by
      immunoaffinity chromatography. Subsequent preparative Western blotting enabled N
      terminal amino acid sequence analysis by microsequencing. A high degree of amino
      acid sequence similarity with eubacterial ribosomal proteins L7/L12 was
      demonstrated. One of the mAbs (144,H-3) also cross-reacted in Western blotting
      with a 43 kDa protein, but only from streptococci. The 43 kDa protein carrying
      the common streptococcal epitope was isolated and sequenced in the N-terminal
      region. A high degree of amino acid sequence identity was found to elongation
      factor Ts from Escherichia coli.

PMID- 9025279
TI  - Endotoxic properties of free lipid A from Porphyromonas gingivalis.
AB  - The relationship between chemical structure and biological activity of the lipid
      A from Porphyromonas gingivalis, which we recently isolated and whose complete
      chemical structure was determined [Kumada et al. (1995). J Bacteriol 177, 2098
      2106], was studied. The lipid A exhibited endotoxic activity in all the assay
      systems tested: Limulus gelation activity, lethal toxicity in galactosamine
      sensitized mice, mitogenicity in mouse spleen cells and induction of nitric oxide
      (NO) and tumour necrosis factor alpha (TNF) release from both mouse peritoneal
      macrophages and the J774-1 mouse macrophage-like cell line. The activity was,
      however, about 100-fold less than that of Salmonella minnesota LPS used as a
      control. The moderate activity of the lipid A may be partially explained by its
      unique fatty acid composition and the lack of a phosphate group in position 4. In
      contrast, the lipid A as well as whole LPS of P. gingivalis unexpectedly
      exhibited an even stronger induction of TNF from the human monocytic THP-1 cell
      line than control LPS when measured by the minimum stimulatory dose. The
      difference in sensitivity of human and mouse cells to P. gingivalis lipid A
      suggests that the recognition mechanism, including that for the receptor for
      endotoxin, may be regulated in different ways in the two cells.

PMID- 9025280
TI  - The lipid A biosynthesis deficiency of the Escherichia coli antibiotic
      supersensitive mutant LH530 is suppressed by a novel locus, ORF195.
AB  - A new mutant of Escherichia coli K-12 supersensitive to both hydrophobic and
      large hydrophilic antibiotics was isolated and characterized. The mutant grew
      well at 28 degrees C, poorly at 37 degrees C, and did not grow at 42 degrees C.
      The rate of its lipid A biosynthesis was reduced as compared to that of the
      parent strain. This deficiency was rescued by a novel locus, ORF195, the function
      of which has not been elucidated. ORF195 is located in the 76 min region in the
      E. coli chromosome and encodes a hypothetical 21.8 kDa protein with no signal
      sequence. ORF195 isolated from the mutant strain had an identical sequence to the
      wild-type allele, indicating a suppressor function of the gene product.

PMID- 9025281
TI  - Thioredoxin is essential for Rhodobacter sphaeroides growth by aerobic and
      anaerobic respiration.
AB  - To investigate the biological role of thioredoxin in the facultative
      photosynthetic bacterium Rhodobacter sphaeroides, attempts were made to construct
      a thioredoxin-deficient mutant by site-specific mutagenesis, using the Tn903
      kanamycin resistance gene for selection. In situ and Southern hybridization
      analyses have demonstrated that the TrxA- mutation is lethal for R. sphaeroides
      growth under anaerobic conditions with DMSO as terminal electron acceptor and
      under aerobic conditions. In addition, the DNA region upstream of the trxA
      initiation codon is essential for aerobic growth of R. sphaeroides. An ORF of
      unknown function was identified in this region and is suggested to encode a
      product essential for aerobic metabolism of R. sphaeroides. The mechanism of
      thioredoxin action was also analysed by using the procedure for gene replacement
      to introduce a Cys33 to Ser mutation into the trxA chromosomal copy. The strain
      carrying this mutation produced a thioredoxin impaired in its protein-disulfide
      reductase activity and was also not viable. These data suggest that the
      physiological function of R. sphaeroides thioredoxin is redox-dependent.
      Thioredoxin purified from R. sphaeroides was shown to have a glutathione
      disulfide oxidoreductase activity typical of glutaredoxins. This unexpected
      finding suggests that R. sphaeroides thioredoxin, in contrast to Escherichia coli
      thioredoxin, has the potential to act in GSH-dependent processes. Thus, the
      fundamental role of R. sphaeroides thioredoxin in cell growth probably originates
      from the multiple functions it can serve in vivo.

PMID- 9025282
TI  - Plasmid-encoded genes specifying aniline oxidation from Acinetobacter sp. strain
      YAA.
AB  - Acinetobacter sp. strain YAA is able to use aniline and o-toluidine as the sole
      carbon and energy source. This strain has several different plasmids and acridine
      orange curing suggested that aniline utilization in strain YAA was plasmid
      encoded. The gene cluster involved in aniline oxidation was cloned in Escherichia
      coli JM109 from the total plasmid DNA of strain YAA. A recombinant E. coli
      containing an 18.5 kb insert fragment showed yellow colouration on aniline
      containing plates, indicating the formation of 2-hydroxymuconic semialdehyde from
      aniline. In addition, subcloning of a 9.0 kb SalI fragment from the insert in E.
      coli resulted in the accumulation of catechol. Southern hybridization studies
      indicated that the aniline oxygenase gene (atdA) was present on one of the
      plasmids, pYA1. These results suggest that in strain YAA aniline is degraded via
      catechol through a pathway involving meta-cleavage of the benzene-ring by plasmid
      encoded genes including atdA.

PMID- 9025283
TI  - XylUW, two genes at the start of the upper pathway operon of TOL plasmid pWW0,
      appear to play no essential part in determining its catabolic phenotype.
AB  - The upper pathway operon of the toluene catabolic pathway of TOL plasmid pWW0 was
      shown to carry two open reading frames between the start of transcription and
      xylC (encoding benzaldehyde dehydrogenase), the first previously reported gene of
      the operon. These were designated xylUW: xylU encoded a protein of 131 amino acid
      residues (M(r) 14,244) which bore no relationship with any protein in the
      databases, and xylW encoded a protein of 348 residues (M(r) 36,992) which was
      strongly homologous to other long-chain Zn-containing alcohol dehydrogenases.
      Extracts of Escherichia coli carrying xylUW in expression vector pTrc99A
      contained a novel protein corresponding to XylW, but no NAD(+)-dependent
      dehydrogenase activity against benzyl alcohol, mandelate or bezylamine. A mini
      Tn5 transposon carrying the meta pathway operon was constructed and from it two
      strains of Pseudomonas putida were constructed with the normally plasmid-encoded
      catabolic operons integrated into the chromosome. Three derivatives of plasmid
      pKNG101 containing modified xylUW genes were constructed, two of which had
      frameshifts in xylU and xylW, respectively, and a third with a deletion from the
      3' end of xylU into the 5' end of xylW. The wild-type genes of the two
      Pseudomonas strains were substituted by the mutant alleles by reverse genetics.
      The ability of the constructed mutant strains to utilize the aromatic substrates
      of the TOL pathway was not significantly affected.

PMID- 9025284
TI  - The plasmid-located haloalkane dehalogenase gene from Rhodococcus rhodochrous
      NCIMB 13064.
AB  - The haloalkane dehalogenase (dhaA) gene from Rhodococcus rhodochrous NCIMB 13064
      was cloned and sequenced. Its comparison with the previously studied dhlA gene
      from Xanthobacter autotrophicus GJ10 did not show homology. However, the amino
      acid sequences of the products of these genes showed approximately 30% identity
      and several of the catalytic amino acid residues were conserved in the NCIMB
      13,064 dehalogenase. A high level of dhaA expression was demonstrated in
      Escherichia coli cells and this gene was shown to encode a dehalogenase with the
      activity against chloroalkanes of chain length C3-C10. Also, some dehalogenase
      activity against 1,2-dichloroethane encoded by the cloned dhaA gene was detected.
      The analysis of NCIMB 13,064 derivatives lacking dehalogenase activity showed
      that the dhaA gene was located on the 100 kbp pRTL1 plasmid. It was also found
      that reversible rearrangements of DNA in the dhaA region may be responsible for
      the control of expression of haloalkane dehalogenase in R. rhodochrous NCIMB
      13064. A number of repeated and inverted sequences which may cause genetic
      instability at the locus were found in the haloalkane dehalogenase gene region.

PMID- 9025285
TI  - ScCypB is a novel second cytosolic cyclophilin from Streptomyces chrysomallus
      which is phylogenetically distant from ScCypA.
AB  - A novel second streptomycete cyclophilin gene-designated sccypB-was isolated from
      a cosmid gene library of Streptomyces chrysomallus by using as gene probe a
      fragment of the previously isolated cyclophilin gene sccypA of the same organism.
      From its sequence the gene sccypB should encode a protein of M(r) 18868.
      Expression of sccypB in Escherichia coli as a hexaHis-tagged fusion protein
      (H6ScCypB) and enzymic characterization of the purified protein showed that, like
      ScCypA, ScCypB is a peptidyl-prolyl cis-trans isomerase (PPIase). The specific
      activity and substrate specificity of the enzyme were comparable to that of
      ScCypA, but it was threefold less sensitive to inhibition by cyclosporin A (CsA).
      In contrast to ScCypA, which is abundant and exists in free and liganded form,
      ScCypB was 50- to 100-fold less abundant in cytosol-derived protein fractions of
      S. chrysomallus or Streptomyces lividans, as revealed by Western blot analyses,
      suggesting a specialized function for this enzyme in the streptomycete cell. Both
      sccypB and sccypA were found to be present as single copies in the genome of S.
      chrysomallus and hybridized to a single band in chromosomal DNAs of other
      streptomycetes. High-level expression of sccypB as well as of sccypA cloned into
      the expression vector pIJ702 did not produce detectable changes in growth and
      morphology of S. chrysomallus and S. lividans. Calculations of similarities to
      known cyclophilin sequences and construction of phylogenetic trees indicated that
      ScCypB and ScCypA are phylogenetically distant from each other. While ScCypA is
      clearly related to the eukaryotic cyclophilins, the analyses show the sequence of
      ScCypB to be the most divergent of all cyclophilin sequences, indicating that it
      possibly constitutes a cluster by itself.

PMID- 9025286
TI  - High affinity iron acquisition in Rhizobium leguminosarum requires the cycHJKL
      operon and the feuPQ gene products, which belong to the family of two-component
      transcriptional regulators.
AB  - The cycHJKL operon of Rhizobium leguminosarum has previously been shown to be
      involved in the maturation of cytochrome c, possibly by its involvement in the
      covalent attachment of haem to the apoprotein. Mutations in the cycHJKL genes
      abolish symbiotic nitrogen fixation. Here, we show that cyc mutants are
      pleiotropically defective. They have lost a high affinity iron acquisition system
      due to their failure to make or to export siderophores. They also accumulate
      protoporphyrin IX, the immediate precursor of haem. A model to account for these
      phenotypes is presented. Immediately upstream of cycH is a gene, lipA, which is
      predicted to encode an outer-membrane lipoprotein. Further upstream of lipA,
      there are two other genes, whose products are similar in sequence to the
      widespread family of two-component transcriptional regulators. These two genes,
      feuP and feuQ, did not affect the transcription of lipA, or of the cycHJKL
      operon. However, a mutation in feuQ also led to the loss of the high affinity
      iron uptake system, although siderophores were still produced.

PMID- 9025287
TI  - An iron-regulated outer-membrane protein specific to Bordetella bronchiseptica
      and homologous to ferric siderophore receptors.
AB  - The bfrA (Bordetella bronchiseptica ferric iron repressed outer-membrane protein)
      gene was cloned from Bordetella bronchiseptica by screening a library of TnphoA
      insertion mutants for iron-repressed fusions to phoA. The bfrA gene encoded an 80
      kDa outer-membrane protein with a high level of amino acid sequence identity to
      several bacterial proteins belonging to the family of Ton B-dependent outer
      membrane receptors. BfrA was especially homologous to Cir of Escherichia coli,
      IrgA of Vibrio cholerae and to three previously characterized ferric enterobactin
      receptors. DNA hybridization results indicated that bfrA was not present in other
      Bordetella species. Expression of the bfrA gene was induced by low iron
      availability from a promoter overlapped by a sequence resembling a consensus Fur
      binding sequence, and bfrA expression was derepressed in a B. bronchiseptica fur
      mutant. Utilization of the Bordetella siderophore alcaligin and the exogenous
      siderophore enterobactin was unaffected in bfrA mutants. Upon attempting to find
      the specificity of BfrA, 2,3-dihydroxybenzoylserine (DHBS) was shown to be
      utilized in a bfeA (Bordetella ferric enterobactin receptor gene)-dependent
      manner by B. bronchiseptica and B. pertussis. In addition, the hydroxamate
      siderophores ferrichrome and desferrioxamine B, and the iron source haemin were
      shown to be utilized independently of bfeA and bfrA in B. bronchiseptica and B.
      pertussis.

PMID- 9025288
TI  - Enterobactin synthase polypeptides of Escherichia coli are present in an osmotic
      shock-sensitive cytoplasmic locality.
AB  - The terminal reactions in the synthesis of the siderophore enterobactin (Ent) by
      Escherichia coli require the EntD, E, F and B/G polypeptides. The idea that these
      molecules form a complex (Ent synthase) that is membrane-associated was re
      evaluated. In vitro results provided no evidence in support of the proposal: (i)
      Ent synthase activity occurred normally under conditions where membrane was
      either absent or disrupted by high concentrations of neutral detergents, and (ii)
      immunoprecipitation experiments conducted on extracts engaged in Ent synthesis
      failed to detect any association among the Ent polypeptides. However, Western
      blot analyses showed that EntE, F and B/G were released from cells by osmotic
      shock and freeze/thaw treatment but not by conversion of cells to spheroplasts.
      These results demonstrated that EntE, F and B/G belong to the Beacham group D
      class of proteins. The shockability of a given group D Ent protein was unaffected
      by the absence of either EntB/G or EntD and, for EntB/G, the N-terminus was
      sufficient for release by osmotic shock. The behaviour of group D proteins is
      generally attributed to their association (partial, loose or transient) with
      cytoplasmic membrane; therefore, the results are indirect evidence that Ent
      synthase interacts with membrane in vivo. At the very least, the data indicate
      that EntE, F and B/G are compartmentalized in E. coli and, because other
      biosynthetic enzymes for siderophores and surfactants are related to these Ent
      proteins, suggest that this entire protein class may be sequestered in vivo.

PMID- 9025289
TI  - BofC encodes a putative forespore regulator of the Bacillus subtilis sigma K
      checkpoint.
AB  - A mutation, bofC1, that restores sigma K activation in Bacillus subtilis strains
      unable to produce active sigma G has been identified. This mutation defines a new
      sporulation gene, bofC, that has been cloned and sequenced and encodes a 19 kDa
      protein. bofC is transcribed in the forespore by RNA polymerase associated with
      the transcription factors sigma F (E sigma F) and sigma G (E sigma G). BofC acts
      negatively on SpoIVB and the results described suggest that BofC regulates SpoIVB
      activity and its intercompartmental signalling role in the sigma K checkpoint.

PMID- 9025290
TI  - A Bacillus cereus member of the SNF2 family.
AB  - The complete sequence of a Bacillus cereus member of the SNF2 family of putative
      helicases showed conservation of all seven motifs typical of this family. Bcsnf
      predicted a protein of 1064 aa where the conserved SNF2 domain was located at the
      carboxy terminus, whereas the 633 amino-terminal aa showed no homology to any
      protein in the databases. A putative transcriptional start was identified by
      primer extension, indicating that Bcsnf is not a part of a larger operon. No
      phenotypical changes were observed after insertional inactivation of Bcsnf. The
      completely sequenced genomes of Mycoplasma genitalium and Haemophilus influenzae
      contain one ORF each with similarity to the SNF2 family: MG018 and HI0616,
      respectively. A phylogenetic tree of the SNF2 family showed that BcSNF and MG018
      were most closely related, and appeared closer to the eukaryotic members of the
      SNF2 family than to the two other bacterial members of the family, HepA from
      Escherichia coli and HI0616.

PMID- 9025291
TI  - A 10.3 kbp segment from nprB to argJ at the 102 degrees region of the Bacillus
      subtilis chromosome.
AB  - The approximately 10 kbp region encompassing nprB and argJ at 102 degrees on the
      Bacillus subtilis chromosome was sequenced, revealing 12 ORFs, four known genes
      (argJ, argC, ipi and nprB) and two genes, yitY and yitS, whose products
      respectively display significant homology with L-gulono-gamma-lactone oxidase of
      rat and dihydrofolate reductase of Staphylococcus aureus. The data also indicated
      that nprB mapped to a different position than previously published.

PMID- 9025292
TI  - Bacteriophage T4 development depends on the physiology of its host Escherichia
      coli.
AB  - Several parameters of phage T4 adsorption to and growth in Escherichia coli B/r
      were determined. All changed monotonously with the bacterial growth rate (mu),
      which was modified by nutritional conditions. Adsorption rate was faster at
      higher mu values, positively correlated to cell size, and increased by
      pretreatment with low penicillin (Pn) concentrations; it was directly
      proportional to total cellular surface area, indicating a constant density of T4
      receptors on cell envelopes irrespective of growth conditions. Parameters of
      phage development and cell lysis were mu-dependent. The rate of phage release and
      burst size increased, while the eclipse and latent periods decreased with
      increasing mu. Differentiation between the contribution of several physiological
      parameters to the development of T4 was performed by manipulating the host cells.
      A competitive inhibitor of glucose uptake, methyl alpha-D-glucoside, was
      exploited to reduce the growth rate in the same effective carbon source.
      Synchronous cells were obtained by the "baby-machine' and large cells were
      obtained by pretreatment with low Pn concentrations. Lysis was delayed by
      superinfection, and DNA content and concentration were modified by growing a thy
      mutant in limiting thymine concentrations. The results indicate that burst size
      is not limited by cell size or DNA composition, nor directly by the rate of
      metabolism, but rather by the rates of synthesis and assembly of phage components
      and by lysis time. The rates of synthesis and assembly of phage components seem
      to depend on the content of the protein-synthesizing system and lysis time seems
      to depend on cellular dimensions.

PMID- 9025293
TI  - The ldhA gene encoding the fermentative lactate dehydrogenase of Escherichia
      coli.
AB  - Under anaerobic conditions, especially at low pH, Escherichia coli converts
      pyruvate to D-lactate by means of an NADH-linked lactate dehydrogenase (LDH).
      This LDH is present in substantial basal levels under all conditions but
      increases approximately 10-fold at low pH. The ldhA gene, encoding the
      fermentative lactate dehydrogenase of E. coli, was cloned using lambda 10E6 of
      the Kohara collection as the source of DNA. The IdhA gene was subcloned on a 2.8
      kb MluI-MluI fragment into a multicopy vector and the region encompassing the
      gene was sequenced. The IdhA gene of E. coli was highly homologous to genes for
      other D-lactate-specific dehydrogenases but unrelated to those for the L-lactate
      specific enzymes. We constructed a disrupted derivative of the ldhA gene by
      inserting a kanamycin resistance cassette into the unique KpnI site within the
      coding region. When transferred to the chromosome, the ldhA::Kan construct
      abolished the synthesis of the D-LDH completely. When present in high copy
      number, the ldhA gene was greatly overexpressed, suggesting escape from negative
      regulation. Cells expressing high levels of the D-LDH grew very poorly,
      especially in minimal medium. This poor growth was largely counteracted by
      supplementation with high alanine or pyruvate concentrations, suggesting that
      excess LDH converts the pyruvate pool to lactate, thus creating a shortage of 3
      carbon metabolic intermediates. Using an ldhA-cat gene fusion construct we
      isolated mutants which no longer showed pH-dependent regulation of the ldhA gene.
      Some of these appeared to be in the pta gene, which encodes
      phosphotransacetylase, suggesting the possible involvement of acetyl phosphate in
      ldhA regulation.

PMID- 9025294
TI  - Use of morphology index histograms to quantify populations of the fungal pathogen
      Paracoccidioides brasiliensis.
AB  - To quantify the dimorphic process in wild and mutant strains of Paracoccidioides
      brasiliensis, we defined a morphology index (Mi) in terms of the maximum cell
      length (l), maximum cell diameter (d), and septal diameter (s), according to the
      equation Mi = 2.13 + 1.13 log10 (ls/d2), whose intercept and slope were such that
      Mi was around 1 for yeast (spherical) cells or 4 for hyphal (elongated) cells.
      This discriminatory power was used to quantify morphological population mixtures
      through Mi histograms. During the temperature-induced dimorphic transition
      (either way), mean Mi (Mi) varied linearly with time, suggesting a continuity in
      the process. Also, in wild strains and mutants thereof we found an inverse
      relationship between Mi and content of both cell wall chitin and 1,3-alpha
      glucan.

PMID- 9025295
TI  - Flux distributions in anaerobic, glucose-limited continuous cultures of
      Saccharomyces cerevisiae.
AB  - A stoichiometric model describing the anaerobic metabolism of Saccharomyces
      cerevisiae during growth on a defined medium was derived. The model was used to
      calculate intracellular fluxes based on measurements of the uptake of substrates
      from the medium, the secretion of products from the cells, and of the rate of
      biomass formation. Furthermore, measurements of the biomass composition and of
      the activity of key enzymes were used in the calculations. The stoichiometric
      network consists of 37 pathway reactions involving 43 compounds of which 13 were
      measured (acetate, CO2, ethanol, glucose, glycerol, NH4+, pyruvate, succinate,
      carbohydrates, DNA, lipids, proteins and RNA). The model was used to calculate
      the production rates of malate and fumarate and the ethanol measurement was used
      to validate the model. All rate measurements were performed on glucose-limited
      continuous cultures in a high-performance bioreactor. Carbon balances closed
      within 98%. The calculations comprised flux distributions at specific growth
      rates of 0.10 and 0.30 h-1. The fluxes through reactions located around important
      branch points of the metabolism were compared, i.e. the split between the pentose
      phosphate and the Embden-Meyerhoff-Parnas pathways. Also the model was used to
      show the probable existence of a redox shunt across the inner mitochondrial
      membrane consisting of the reactions catalysed by the mitochondrial and the
      cytosolic alcohol dehydrogenase. Finally it was concluded that cytosolic
      isocitrate dehydrogenase is probably not present during growth on glucose. The
      importance of basing the flux analysis on accurate measurements was demonstrated
      through a sensitivity analysis. It was found that the accuracy of the
      measurements of CO2, ethanol, glucose, glycerol and protein was critical for the
      correct calculation of the flux distribution.

PMID- 9025296
TI  - Expulsion of uracil and thymine from the yeast Saccharomyces cerevisiae:
      contrasting responses to changes in the proton electrochemical gradient.
AB  - The outflow of uracil from the yeast Saccharomyces cerevisiae is known to be
      relatively fast in certain circumstances, to be retarded by proton conductors and
      to occur in strains lacking a uracil proton symport. In the present work, it was
      shown that uracil exit from washed yeast cells is an active process, creating a
      uracil gradient of the order of -80 mV relative to the surrounding medium.
      Glucose accelerated uracil exit, while retarding its entry. DNP or sodium azide
      each lowered the gradient to about -30 mV, simultaneously increasing the rate of
      uracil entry. They also lowered cellular ATP content. Manipulation of the
      external ionic conditions governing delta mu H+ at the plasma membrane had no
      detectable effect on uracil transport in yeast preparations thoroughly depleted
      of ATP. It was concluded that uracil exit is probably not driven by the proton
      gradient but may utilize ATP directly. It is known that thymine is not normally
      absorbed by yeast. However, thymine expulsion was here observed during
      deamination of the substrate 5-methylcytosine in the presence of glucose. In the
      absence of glucose, or following ATP depletion, thymine uptake from the medium
      only occurred when delta mu H+ was dissipated, either by DNP or azide, or by
      manipulation of the external ionic environment. The yeast expelled absorbed
      thymine when delta mu H+ was restored to the physiological range. The properties
      of the system corresponded to those of an H+/thymine antiport that is distinct
      from the mechanism expelling uracil.

PMID- 9025297
TI  - Expression of CEL2 and CEL4, two proteins from Agaricus bisporus with similarity
      to fungal cellobiohydrolase I and beta-mannanase, respectively, is regulated by
      the carbon source.
AB  - Two new cellulose-growth specific (cel) cDNAs, cel2 and cel4, have been isolated
      from an Agaricus bisporus cDNA expression library by immunoscreening with an A.
      bisporus anti-'endoglucanase' antibody. The deduced amino acid sequences showed
      that both CEL2 and CEL4 proteins have a modular structure consisting of a fungal
      type cellulose-binding domain (CBD) and a catalytic domain separated by a linker
      region rich in Pro, Ser and Thr. The CEL2 and CEL4 catalytic domains were
      homologous to fungal cellobiohydrolases (CBH) in family 7 and to fungal
      mannanases in family 5 of the glycosyl hydrolases, respectively. A previously
      isolated cDNA derived from a constitutive gene was also sequenced. The deduced
      amino acid sequence corresponded to 5-aminolaevulinic acid synthase (ALA), the
      first enzyme in the haem biosynthetic pathway, and was most similar to other
      fungal ALAs. RNA analysis showed that the expression of cel2 and cel4 genes was
      induced by cellulose and repressed by glucose, fructose and lactose. The soluble
      cellulose derivative CM-cellulose induced mRNA accumulation for cel1 but not
      cel2, cel3 or cel4. Mannitol, maltose, sorbitol and glycerol decreased cel2 and
      cel4 mRNA levels to different extents. cel1, cel2, cel3 and cel4 mRNAs all
      disappeared after the addition of glucose with apparent half-lives of less than
      20 min. Whether cel mRNAs have short half-lives or glucose affects the stability
      of cel transcripts remains to be investigated.

PMID- 9025298
TI  - The phytase subfamily of histidine acid phosphatases: isolation of genes for two
      novel phytases from the fungi Aspergillus terreus and Myceliophthora thermophila.
AB  - Phytases catalyse the hydrolysis of phytate (myo-inositol hexakisphosphate) to
      myo-inositol and inorganic phosphate. In this study genes encoding novel phytases
      from two different filamentous fungi, Aspergillus terreus strain 9A-1 and
      Myceliophthora thermophila were isolated. The encoded PhyA phytase proteins show
      60% (A. terreus) and 48% (M. thermophila) identity, respectively, to the PhyA of
      Aspergillus niger and have 21-29% identity compared to other histidine acid
      phosphatases. All three PhyA proteins, in contrast to the A. niger pH 2.5-optimum
      acid phosphatase, prefer phytic acid as substrate and show enzyme activity at a
      broad range of acidic pH values. Based on their enzyme characteristics and
      protein sequence homology, the phytases form a novel subclass of the histidine
      acid phosphatase family.

PMID- 9025299
TI  - AtDMC1, the Arabidopsis homologue of the yeast DMC1 gene: characterization,
      transposon-induced allelic variation and meiosis-associated expression.
AB  - Based on homologies between the yeast DMC1 and the lily LIM15 meiosis-specific
      genes, degenerate PCR primers were designed that amplified the Arabidopsis DMC1
      gene (AtDMC1). AtDMC1 genomic DNA (8 kb) was sequenced, and the transcript was
      characterized by reverse transcriptase-polymerase chain reaction (RT-PCR) and by
      5' and 3' RACE (rapid amplification of cDNA ends). The AtDMC1 gene contains 15
      exons and 14 introns. RNA in situ hybridization analysis showed that expression
      of the AtDMC1 is restricted to pollen mother cells in anthers and to megaspore
      mother cells in ovules. The AtDMC1 promoter was fused to the GUS reporter gene,
      and conferred meiosis-associated expression in both male and female floral
      lineages. Comparison of AtDMC1 isolated from Landsberg erecta ecotype to its
      Columbia allele ArLIM15, revealed the presence of a 1874 bp transposon-like
      element within the promoter region of ArLIM15. RT-PCR analysis showed that the
      expression levels of AtDMC1 and ArLIM15 are similar. Possible uses for the AtDMC1
      promoter are discussed.

PMID- 9025300
TI  - T-DNA integration patterns in co-transformed plant cells suggest that T-DNA
      repeats originate from co-integration of separate T-DNAs.
AB  - Nicotiana protoplasts and Arabidopsis leaf discs or roots were co-cultivated with
      two Agrobacterium strains each carrying a different T-DNA. Co-transformed plants
      were selected and the integration of the different T-DNAs was analysed at the
      genetic and genomic level. Genetic analysis showed that the T-DNAs derived from
      different bacteria were frequently integrated at the same locus, independent of
      the plant species or transformation method used. Southern analysis revealed that
      12 out of 27 Arabidopsis transformants contained the co-transferred T-DNAs linked
      to each other in all possible configurations but with a preference for those with
      at least one right border involved in linkage. Overall, our data support the
      hypothesis that ligation of separate T-DNAs is a dominant mechanism in formation
      of the frequently observed repeats of identical T-DNAs. We propose a scheme which
      could explain the formation of T-DNA repeats and the preferential involvement of
      right borders in T-DNA linkages.

PMID- 9025301
TI  - Molecular cloning of a new receptor-like kinase gene encoded at the Lr10 disease
      resistance locus of wheat.
AB  - More than 100 resistance genes against wheat rust pathogens have been described
      in wheat and its relatives. Although many of them have been extensively used in
      wheat resistance breeding, none of these resistance loci has yet been analyzed at
      the molecular level. By screening a set of near-isogenic lines carrying different
      leaf rust resistance genes with a wheat probe encoding a serine/ threonine
      protein kinase, we detected a polymorphic DNA fragment in the line with the Lr10
      resistance gene. This fragment mapped to the Lr10 disease resistance locus and
      encodes a receptor-like protein kinase which we called LRK10. LRK10 contains a
      new type of extracellular domain not found in known plant or animal receptor
      kinases. Several conserved amino acids in S-domain glycoproteins and receptor
      like kinases were also found in LRK10, suggesting that LRK10 and S-domain
      proteins belong to the same superfamily of specific recognition molecules in
      plants. Lrk10 was expressed at low levels in young seedlings and belongs to a
      gene family. Analysis of wheat lines with and without the Lr10 gene demonstrated
      that Lrk10 and Lr10 belong to the same genetic locus. We conclude that gene
      isolation based on protein kinase homology can identify new receptor domains and
      provide candidates for disease resistance genes in the complex wheat genome.

PMID- 9025302
TI  - Identification of mutants in metabolically regulated gene expression.
AB  - Sucrose is the main transported form of assimilates, but, significantly, it also
      regulates a variety of processes such as photosynthesis and carbon or nitrogen
      storage. The effects of high sucrose levels are mediated directly by modulation
      of gene expression. The regulation of storage protein accumulation, here patatin
      from potato tubers, was used as a model system to study sucrose mediated signal
      transduction. The transcriptional regulation of patatin genes in conserved in
      transgenic Arabidopsis, as shown by the analysis of expression of two classes of
      patatin promoters fused to uidA. Two distinctly different patterns of gene
      expression were observed. In roots, class I promoter expression is strongly
      dependent on the exogenous supply of sugars. 3-O-methylglucose induction
      indicates that the sensor is located upstream of hexokinase. In contrast, the
      class II promoter is constitutively active in root tips and hydatodes. The
      progeny of a homozygous class I line was mutagenized with ethyl methane
      sulphonate and screened for signal transduction mutants using a non-destructive
      screening system for GUS activity. Four mutants showing reduced sucrose responses
      (rsr) and two mutants with modified expression patterns (mep) regarding the root
      tip were identified. In backcross analyses, it was shown that rsr1-1 carries a
      recessive trans mutation whereas rsr4-1 seems to be a semi-dominant trans
      mutation in sugar-mediated gene regulation.

PMID- 9025303
TI  - Characterization of a novel eukaryotic ATP/ADP translocator located in the
      plastid envelope of Arabidopsis thaliana L.
AB  - Recently, we have sequenced a cDNA clone from Arabidopsis thaliana L. encoding a
      novel putative ATP/ADP translocator (AATP1). Here, we demonstrate that the
      radioactively labeled AATP1 precursor protein, synthesized in vitro, is targeted
      to envelope membranes of isolated spinach chloroplasts. Antibodies raised against
      a synthetic peptide of AATP1 recognized a single polypeptide of about 62 kDa in
      chloroplast inner envelope preparations. The cDNA coding for the AATP1 protein
      was functionally expressed in Saccharomyces cerevisiae and Escherichia coli. In
      both expression systems, increased rates of ATP transport were observed after
      reconstitution of the extracted protein into proteoliposomes. To our knowledge,
      this is the first report on the functional expression of an intrinsic plant
      membrane protein in E. coli. To yield high rates of ATP transport,
      proteoliposomes had to be preloaded with ADP, indicating a counter-exchange mode
      of transport. Carboxyatractyloside did not substantially interfere with ATP
      transport into proteoliposomes containing the plastidic ATP/ADP translocator. An
      apparent KM for ATP of 28 microM was determined which is similar to values
      reported for isolated plastids. The data presented here strongly support the
      conclusion that AATP1 represents a novel eukaryotic adenylate carrier and that it
      is identical with the so far unknown plastidic ATP/ADP translocator.

PMID- 9025304
TI  - The cloning of two Arabidopsis genes belonging to a phosphate transporter family.
AB  - Two genes, APT1 and APT2, with DNA sequences that exhibit significant sequence
      identity to yeast and fungal H+/orthophosphate co-transporters, have been
      isolated from Arabidopsis thaliana. These genes are genetically linked and map to
      chromosome 5 between markers g4028 and m435. The genes encode almost identical
      524 amino acid polypeptides and are predicted to contain 12 membrane-spanning
      domains. Both APT1 and APT2 are predominantly expressed in A. thaliana root
      tissues. The level of expression of both genes in roots is regulated by the
      phosphorus status of the plant, being considerably enhanced when the plants were
      deprived of an external phosphate supply. The APT1 and APT2 polypeptides are
      likely to be associated with the membrane transport of phosphate within A.
      thaliana roots.

PMID- 9025305
TI  - Characterization of proteins that interact with the GTP-bound form of the
      regulatory GTPase Ran in Arabidopsis.
AB  - Ran, a small soluble GTP-binding protein, has been shown to be essential for the
      nuclear translocation of proteins and it is also thought to be involved in
      regulating cell cycle progression in mammalian and yeast cells. Genes encoding
      Ran-like proteins have been isolated from different higher plant species.
      Overexpression of plant Ran cDNAs, similarly to their mammalian/yeast homologues,
      suppresses the phenotype of the pim46-1 cell cycle mutant in yeast cells. The
      mammalian/yeast Ran proteins have been shown to interact with a battery of Ran
      binding proteins, including the guanidine nucleotide exchange factor RCC1, the
      GTPase-activating Ran-GAP, nucleoporins and other Ran-binding proteins (RanBPs)
      specific for Ran-GTP. Here, the characterization of the first Ran-binding
      proteins from higher plants is reported. The yeast two-hybrid system was used to
      isolate cDNA clones encoding proteins of approximately 28 kDa (At-RanBP1a, At
      RanBP1b) that interact with the GTP-bound forms of the Ran1, Ran2 and Ran3
      proteins of Arabidopsis thaliana. The deduced amino acid sequences of the At
      RanBP1s display high similarity (60%) to mammalian/yeast RanBP1 proteins and
      contain the characteristic Ran-binding domains. Furthermore, interaction of the
      plant Ran and RanBP1 proteins, is shown to require the acidic C-terminal domain (
      DEDDDL) of Ran proteins in addition to the presence of an intact Ran-binding
      domain. In whole cell extracts, the GST-RanBP1a fusion protein binds specifically
      to GTP-Ran and will not interact with Rab/Ypt-type small GTP-binding proteins.
      Finally, in good agreement with their proposed biological function, the At-Ran
      and the At-RanBP genes are expressed coordinately and show the highest level of
      expression in meristematic tissues.

PMID- 9025306
TI  - Regulation of flavonol biosynthesis during anther and pistil development, and
      during pollen tube growth in Solanum tuberosum.
AB  - The regulation of flavonol biosynthesis was studied in anthers and pistils of
      Solanum tuberosum. Flavonols are essential for functional pollen tube growth in a
      number of species. Flavonol accumulation in whole anthers started at the
      unicellular stage of pollen development and continued until pollen maturity. A
      cDNA clone encoding flavonol synthase (FLS) was isolated. Fls gene expression was
      detected in pistils, anthers, petals and ovaries, the organs in which flavonols
      are accumulating. Fls transcripts were present in unicellular and bicellular
      pollen, but not in mature pollen. The expression patterns of three genes encoding
      enzymes in the flavonoid biosynthetic pathway, chalcone synthase (chs), flavanone
      3-hydroxylase and fls were analysed in developing anthers and pistils. Only chs
      transcripts accumulated concomitantly with the flavonols in anthers. In pistils
      of potato, pollen tube growth induced an increase in fls gene expression that,
      unlike the situation in pollinated pistils of petunia, did not result in an
      increased flavonol content. Flavonol biosynthesis in anthers is probably
      initiated by the expression of the chs gene, and flavonol accumulation in pistils
      upon pollen tube growth is not an universal phenomenon.

PMID- 9025307
TI  - Ds excision from extrachromosomal geminivirus vector DNA is coupled to vector DNA
      replication in maize.
AB  - Analysis of transposition products generated after Activator (Ac) excision from
      the P locus in maize suggest that Ac excises either during or after replication
      of the P locus. The frequency of excision of the non-autonomous Ac derivative,
      Dissociation (Ds), from extrachromosomal replicating and nonreplicating vector
      DNAs in transfected black mexican sweet maize protoplasts was compared to assess
      directly a role of extrachromosomal vector DNA replication in Ds excision.
      Replicating (rep+) and nonreplicating (rep-) vector DNAs comprised a Ds element
      that harbored a geminivirus, wheat dwarf virus (WDV), origin of replication and
      WDV genes required for viral DNA replication (rep+) or mutant, inactive
      derivatives of these genes (rep-). Excision of Ds was detected only in those cell
      nuclei co-transfected with the replicating Ds-vector DNA and a transposase
      expression vector. Quantitative reconstruction experiments showed that Ds excised
      at least 3 x 10(5)-fold more frequently from replicating vector DNA as compared
      with nonreplicating vector DNA. Therefore, these results provide direct evidence
      for a coupling of Ds excision from extrachromosomal vector DNA to vector DNA
      replication in maize.

PMID- 9025308
TI  - Ds elements on all five Arabidopsis chromosomes and assessment of their utility
      for transposon tagging.
AB  - The maize transposons Activator (Ac) and Dissociation (Ds) tend to transpose to
      sites close to their original position and can be efficiently used to transposon
      tag genetically linked genes. To facilitate this approach, we describe the
      locations of seven T-DNAs carrying Ds elements, including at least one on each of
      the five chromosomes. For five of these T-DNAs, we have confirmed that the Ds
      element transposes preferentially to genetically linked sites. A large-scale
      transposon-tagging experiment was performed by activating Ds from eight
      chromosomal locations that included at least one on each of the five chromosomes.
      These experiments produced a total of 1132 F3 families that were predicted to
      carry around 870 independent Ds insertions. In these populations, 33
      independently isolated mutants that were visibly different from wild-type were
      identified. Twenty-nine of these mutants were studied genetically, and 14 were
      not tagged with Ds because the element could be separated from the mutation by
      recombination. The remaining 15 mutations were possibly tagged because the
      transposon and the mutation were not separated by recombination. These
      experiments provide tools for transposon-tagging on each chromosome, and indicate
      that approximately 50% of identified mutations are likely to be tagged, thereby
      enabling cloning of the affected genes.

PMID- 9025309
TI  - Development of a simple transient assay for Ac/Ds activity in cells of intact
      barley tissue.
AB  - The development of a barley (Hordeum vulgare L.) transformation system made it
      possible to consider the use of maize Activator/Dissociation (Ac/Ds) transposable
      elements for gene tagging in transgenic barley plants. However, barley
      transformation is time-consuming, and therefore a simple transient assay for
      Ac/Ds activity in intact barley tissues was developed to test the components of a
      proposed gene tagging system, prior to their stable introduction into plants. In
      this assay, barley scutellar tissue is co-transformed with constructs containing
      the maize Ac transposase gene and an Escherichia coli uidA reporter gene (Gus),
      the expression of which is interrupted by a maize Ds element. In transformed
      barley scutellar cells, Ac transposase-mediated excision of the Ds element
      generates a functional Gus gene, leading to histochemically detectable GUS
      activity. Characterization of the excision products showed that they had a
      pattern of nucleotide deletions and/or transversions similar to that found in
      maize and other heterologous plant systems. In addition, although contrary to the
      situation observed in heterologous dicot systems, efficient Ds excision in
      barley, a heterologous monocot system, appears to be inversely associated with Ac
      copy number, a finding similar to the Ac dosage effects observed in maize. The
      transient assay was used to demonstrate functional transposase activity in barley
      callus lines stably transformed with an Ac transposase gene.

PMID- 9025310
TI  - Frequency-dependent maintenance of left handedness in humans.
AB  - The percentage (10-13%) of left handedness in human has apparently not changed
      since the Neolithic. Left handedness is heritable and appears to be repeatedly
      associated with some reduced fitness components; the persistence of left
      handedness implies that left handers have a fitness advantage in some situations.
      We propose that left handers have a frequency-dependent advantage in fights and
      for that reason a fitness advantage. To test this hypothesis, left handedness
      frequencies in the general population and in sporting individuals (both students
      and the sporting elite) have been compared, as sporting performance is likely to
      be a good indicator of fighting abilities. The higher proportion of left-handed
      individuals in interactive sports (reflecting some fighting elements), reaching
      50% in some sports categories, but not in noninteractive sports, is consistent
      with the fighting hypothesis. The greater frequency of left handedness in males
      than in females is also consistent with this hypothesis, as male-male fights are
      universally more frequent than other combinations. The frequency-dependent
      advantage in fights of left handers might explain the stability of left
      handedness.

PMID- 9025311
TI  - First gene on the avian W chromosome (CHD) provides a tag for universal sexing of
      non-ratite birds.
AB  - The avian W chromosome shares many features with the mammalian Y chromosome: it
      is small, mostly heterochromatic, and filled with large repetitive arrays. No
      gene so far been assigned to the W chromosome in any bird species and, as a
      practical consequence, a general tag for avian gender identification on the
      molecular level is lacking. Here I describe the isolation of a chicken homologue
      to the mouse chromo-helicase-DNA binding (CHD) gene which encodes a protein
      involved in global regulation of transcriptional activation on the chromatin
      level. The avian CHD gene exists in two genomic copies, one of which termed CHD
      W) was located on the W chromosome in all non-ratio species investigated. The
      gene displays extreme levels of sequence conservation since chicken CHD-W and
      mouse CHD are 82.9% and 95.6% identical at the nucleotide and amino acid level
      respectively. Molecular sexing can be accomplished in probably all non-ratite
      birds by hybridizing Southern blots with CHD probes, PCR-based gender
      identification is also demonstrated. A general system for avian sexing should
      facilitate many studies of behaviour, evolutionary ecology, genetics, and
      evolution.

PMID- 9025312
TI  - Molecular documentation of polyembryony and the micro-spatial dispersion of
      clonal sibships in the nine-banded armadillo, Dasypus novemcinctus.
AB  - A battery of allelic markers at highly polymorphic microsatellite loci was
      developed and employed to confirm genetically, the clonal nature of sibships in
      nine-banded armadillos. This phenomenon of consistent polyembryony, otherwise
      nearly unknown among the vertebrates, was capitalized upon to describe the micro
      spatial distributions of numerous clonal sibships in a natural population of
      armadillos. Adult clone mates were significantly more dispersed than were
      juvenile sibs, suggesting limited opportunities for altruistic behavioural
      interactions among mature individuals. These results, and considerations of
      armadillo natural history, suggest that evolutionary explanations for
      polyembryony in this species may not reside in the kinds of ecological and kin
      selection theories relevant to some of the polyembryonic invertebrates. Rather,
      polyembryony in armadillos may be associated evolutionarily with other
      reproductive peculiarities of the species, including delayed uterine implantation
      of a single egg.

PMID- 9025313
TI  - Costs of resistance: a test using transgenic Arabidopsis thaliana.
AB  - Evolutionary biologists have long attributed polymorphisms in resistance status
      to fitness costs of resistance traits. Nevertheless, pleiotropic fitness costs of
      resistance have been notoriously difficult to detect. We have transformed
      Arabidopsis thaliana with a mutant acetolactate synthase gene that confers
      resistance to the herbicide, chlorsulfuron. Our experiment revealed a 34%
      reduction in the lifetime seed production of transgenic, herbicide resistant
      Arabidopsis thaliana relative to their susceptible null segregants. Our
      experimental design allows us to conclude that this fitness cost of resistance is
      caused by the pleiotropic effect of the introduced acetolactate synthase gene
      rather than other potential costs associated with the plasmid or mutational
      changes induced by plant transformation. In addition, we can attribute the cost
      of resistance to the presence of the resistance gene rather than an increase in
      gene dosages. The implications of these results for the risk assessment of
      transgenic crops are discussed.

PMID- 9025314
TI  - Behavioural sex change in the absence of gonads in a coral reef fish.
AB  - It is an axiom of vertebrate behavioural endocrinology that full expression of a
      male behavioural phenotype depends on testicular influences during development,
      in adulthood, or both. Sex change in fishes challenges this necessity:
      behavioural changes are often rapid and greatly precede gonadal changes. However,
      steroid hormones can have fast actions on the nervous system, so gonadal
      influences on behavioural sex change cannot be excluded based solely on the speed
      of these changes. We report that surgical gonad removal does not prevent or
      discernibly alter female-to-male behavioural sex change in a protogynous coral
      reef fish. Male behaviour assumption is instead purely dependent on attaining
      social dominance. This is the first example of a vertebrate fully expressing a
      male behavioural phenotype without current or previous exposure to a functioning
      testis or testicular products.

PMID- 9025315
TI  - Megatherium, the stabber.
AB  - The traditional point of view that fossil ground sloths (Xenarthra) were a
      relatively uniform, ecologically little diverse group has been recently
      challenged. Marine habits have been ascribed to Thalassocnus natans of the
      Pliocene of Peru. Also, a more diverse diet has been proposed by one of us
      (R.A.F.) for some Lujanian (late Pleistocene-early Holocene of South America
      genera of ground sloths. In this paper, an aspect of this latter hypothesis is
      tested, i.e. that Megatherium americanum had morphological features that are
      better explained by its having had carnivorous habits rather than by solely
      herbivorous ones. Specifically, the question of its forearms having been designed
      for optimizing speed rather than strength of extension is addressed. Such a trait
      might have been associated with a potentially aggressive use of the animal large
      claws, whereas a strong extension would be more proper for tearing branches out.
      On the other hand the high mechanical advantage of the biceps might have made it
      possible for the animal to have lifted and carried heavy weights. This in turn,
      suggests the possibility that the animal could have manipulated large prey (for
      instance, turning dorsally armoured preys or carcasses upside down to expose
      softer parts and cached large food pieces in a safer place. By this view,
      Megatherium americanum would be the largest land mammal hunter to have existed.

PMID- 9025316
TI  - Nitric oxide is necessary for visual learning in Octopus vulgaris.
AB  - We recently reported that inhibition of nitric oxide synthase (NOS) in Octopus
      vulgaris by intramuscular injections of an analog of L-arginine, N-omega-nitro-L
      arginine methyl ester (L-NAME), blocked touch learning in Octopus vulgaris. The
      inactive enantiomorph (D-NAME), which had no effect on learning, was used for
      control. We now report that essentially the same procedures block visual learning
      in this animal. We used a visual paradigm in which the octopus was trained to
      respond positively to a smooth black plastic ball 2.5 cm diameter and negatively
      to a similar white ball, or vice versa. One set of eight animals was trained to
      the black ball positive, and another set of six to the white ball positive. Each
      set was trained at different times by two different trainers. We found that a 1 h
      pretreatment with the nitric oxide synthase inhibitor L-NAME blocks visual
      learning in Octopus vulgaris in both sets of animals.

PMID- 9025317
TI  - Learning to find your way: a role for the human hippocampal formation.
AB  - The importance of the hippocampal formation of the brain for allocentric spatial
      mapping of the environment has been suggested by animal lesion and
      electrophysiological work. Here we describe a positron emission tomography (PET)
      study designed to investigate the regional cerebral blood flow changes associated
      with topographical memory formation in humans, i.e. the formation of
      representations of large-scale environments necessary for way-finding.
      Topographical learning of an urban environment from viewing of film footage
      depicting navigation was associated with activation of the right parahippocampal
      gyrus and hippocampus, with activation also of the left parahippocampal gyrus. In
      addition, there was activity in the pretuneus. In contrast, the encoding of non
      navigation episodic memory in a similar realworld context was not associated with
      activity in the hippocampal formation. Our results shed light on the neural basis
      of the human representation of large-scale space pinpointing a particular role
      for the human hippocampal formation in learning to find one's way.

PMID- 9025318
TI  - Chicken erythrocyte nucleosomes have a defined orientation along the linker DNA-
      a scanning force microscopy study.
AB  - The orientation of nucleosomes was investigated using scanning force microscopy
      (SFM) of hypotonically spread chicken chromatin. A virtual cross section parallel
      to the substrate at half maximum height of the nucleosomal structure revealed an
      elliptical shape. The orientation of the major axis of this ellipse was
      investigated in reference to the direction of the axis of the nucleosomal chain.
      An alignment of the nucleosomes along the nucleosomal chain was observed, with
      more than 50% of the nucleosomes aligned with the long axis of the chain within <
      or = 30 degrees deviation. The alignment distribution peaked at 10-20 degrees.
      The application of SFM-based image processing for the structural investigation of
      a protein-DNA complex demonstrates the potential for this approach in structural
      molecular biology.

PMID- 9025319
TI  - Occupational exposure amongst locomotive shed workers and welders using neutron
      activation analysis of scalp hair.
AB  - Elemental analysis of scalp hair of locomotive shed workers and industrial
      welders was used to study occupational exposure. Instrumental neutron activation
      analysis (INAA) was used for the determination of 17 elements, Ba, Br, Ca, Co,
      Cr, Cu, Fe, Hg, K, Mn, Na, P, Sb, Sc, Se, Th and Zn. Most elements show normal
      distribution at 95% confidence level. Further statistical significance was tested
      by correlation coefficient and regression coefficients (r2). Comparison of mean
      elemental contents of the subjects with controls shows a significant enhancement
      of Ca, Cr, Fe, Co, Na, Sc and Th, but declining trends for Br, Cu, P, Sb and Zn
      in locomotive shed workers. In the case of welders: Ba, Co, Cu, K, Mn, Sc and Sb
      show enhancement whereas Br, Cr, Hg, Se, Th and Zn exhibit depletion. Elemental
      contents have been correlated with possible sources of origin. Comparison of mean
      elemental data for the present population around Nagpur city matches well with
      the reported data for Bombay and Delhi. Comparative data from other countries are
      also presented.

PMID- 9025320
TI  - Instrumental neutron activation analysis of essential and toxic elements in child
      and adolescent diets in the Chernobyl disaster territories of the Kaluga Region.
AB  - The main etiologic factor of various diseases, syndromes and pathologic
      conditions is an excess, deficiency or imbalance of trace element intake into the
      human body. Children seem to be the most sensitive to each change of trace
      element homeostasis. An inadequate essential trace element intake may result in
      an undesirable consequence that can apparently multiply against a background of
      additional unfavourable environmental influence such as high levels of radiation,
      organic and inorganic toxins, etc. Thus, the quality control of children's diets
      assumes urgent importance within the regions covered by the Chernobyl disaster.
      Instrumental neutron activation analysis was used to estimate contents of Ag, Br,
      Ca, Cl, Co, Cr, Cs, Fe, Hg, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn in the
      diets of children and adolescents. Diets were chosen from day care centre,
      boarding school and technical college cafeterias situated within the south and
      south west territories of the Kaluga Region, where radionuclide contamination
      ranges up to 15 Ci/km2. Ca and Zn deficiencies were found in the diets of
      children and adolescents aged 7-18. The Ca intake is only 212 mg/day, 5 times
      lower than that in developed countries. The Zn intake is 6.8 mg/day, 2 times
      lower than the level recommended by the WHO.

PMID- 9025321
TI  - Polyelectrolyte complexes as vehicles for affinity precipitation of proteins.
AB  - Polyelectrolyte complexes (PECs) were formed with polyethylene imine (PEI) and
      polyacrylic acid sodium salt (PA). The aqueous solubility of such PLCs is
      dependent on the stoichiometry between the polymers, the charge densities of the
      polymers and salts present in the solution. Cibacron blue 3GA (CB) was coupled to
      the PEI and the PECs were used for affinity precipitation of lactate
      dehydrogenase (LDH) in beef heart extracts. The affinity precipitation was
      induced by a shift in pH, while the desorption and separation of LDH from the
      PECs was performed by addition of KCl combined with a shift in pH. LDH was
      obtained with a yield of 85% and a purification factor of approx. 11-fold. The
      polymers were recovered and reused once and the results became similar. Prior to
      the affinity precipitation, interfering nucleic acids were removed by
      precipitation with PEI.

PMID- 9025322
TI  - Cloning and expression of pyranose oxidase cDNA from Coriolus versicolor in
      Escherichia coli.
AB  - Complementary DNA encoding pyranose oxidase (PROD) was cloned and sequenced for
      the first time from Coriolus versicolor. The nucleotide sequence revealed an open
      reading frame encoding a polypeptide composed of 623 amino acid residues.
      Compared with the experimentally determined N-terminal sequence of the PROD from
      C. versicolor. 38 amino acids from the N-terminus of the protein appeared to be
      eliminated during protein maturation. The cDNA was successfully expressed under
      the control of lacUV5 promoter in Escherichia coli at 25 degrees C, which will be
      beneficial in industrial production.

PMID- 9025323
TI  - Expression and characterization of a mouse/human chimeric antibody specific for
      EGF receptor.
AB  - Murine antibodies which recognize the epidermal growth factor receptor (EGF-r)
      are good candidates for therapy and diagnosis of tumors overexpressing this
      receptor. Here we report the isolation of the variable regions from a murine
      monoclonal antibody anti-EGF-r (Mint5), the procedure to obtain the mouse/human
      chimeric antibody (chMint5) and its expression in COS, NS0 and CHO cells. The
      approach followed to construct chMint5 is based on the use of consensus primers
      specific for the ends of the variable regions. The sequence imposed by the
      primers did not affect the targeting potential of the antibody. In fact, the
      affinity of the chimeric antibody for EGF-r was nearly the same as that of the
      parental murine antibody. Based on previous in vitro and in vivo animal studies.
      Mint5 was shown to be a good candidate for the targeting of EGF-r overexpressing
      tumours. chMint5 is expected to be less immunogenic than murine antibody and
      therefore, could be useful for human treatment.

PMID- 9025324
TI  - Case report: pathomorphology of an experimental disseminated Aspergillus
      fumigatus infection in rabbits.
AB  - In following a formerly successful protocol designed to produce antibodies to A.
      fumigatus (Fres) we observed a disseminated, lethal fungal infection in healthy,
      specific pathogen-free (SPF) rabbits. The pathomorphological findings included
      multiple miliary to avenaceous whitish nodules in the livers and kidneys, mycotic
      mesencephalitis, nephritis, hepatitis, myocarditis, hemorrhagic enteritis, and
      splenitis. The hyphae were surrounded by necrosis, which also occurred in the
      liver without the hyphae. Comparative gas chromatographic and metabolic
      investigations on this strain and some environmental A. fumigatus strains showed
      significant differences. The findings are discussed with particular reference to
      the pathogenicity of A. fumigatus.

PMID- 9025325
TI  - Negative priming without overt prime selection.
AB  - The procedure typically used to demonstrate negative priming requires subjects to
      respond to one of two simultaneously presented stimuli across two consecutive
      displays. Negative priming is defined by slower responses to targets in the
      second display that appeared as distractors in the first display, than to targets
      in the second display that did not appear in the first display. It is widely
      assumed that negative priming occurs as a result of the selection that occurs in
      the first display. In the present article, we show that negative priming can be
      observed without requiring subjects to respond selectively to one of two items in
      the first display. We argue that this result is useful for two reasons. First, it
      points out a fundamental misunderstanding concerning the procedure required to
      measure negative priming, a misunderstanding that has shaped much of the
      theoretical work done in this area. Second, we suggest that the procedure
      introduced here is of considerable utility in evaluating theoretical accounts of
      negative priming. To demonstrate this utility we report the results of two
      studies that assess the code co-ordination account of negative priming.

PMID- 9025326
TI  - The effect of stimulus range on perceived contrast: evidence for contrast gain
      control.
AB  - In audition, loudness matches across frequency are affected by the range of
      stimuli employed at each frequency (e.g., Marks, 1988; Schneider & Parker, 1990).
      For example, the loudness of a 500-Hz tone that matches the loudness of a 60-dB 2
      kHz tone can be changed by as much as 10 to 20 dB by manipulating the range of
      intensity values to which the listener is exposed. The goal of the present study
      was to determine whether stimulus range had a similar effect on the perceived
      contrast of vertical gratings whose spatial frequencies were either 1 or 4
      cycles/deg. Viewers judged the perceived contrasts of 1 and 4 cycle/deg gratings
      intermixed within a session using the method of magnitude estimation. Four
      different conditions were created by combining either a set of low-contrast or
      high contrast gratings at one frequency with a broad range of contrasts at the
      other frequency. When the broad-range set was at 1 cycle/deg, contrast matches
      across spatial frequencies were unaffected by changing the range of the 4
      cycle/deg gratings from low to high. However, when the broad-range set was at 4
      cycles/deg, contrast matches were changed by changing the range of the 1
      cycle/deg gratings. This asymmetry in the "range effect" was shown to be
      consistent with the characteristics of the two channels' receptive-field
      profiles.

PMID- 9025327
TI  - Choosing category or complementary relations: prior tendencies modulate
      instructional effects.
AB  - Concepts in semantic memory are associated with other categorically (e.g., dog
      horse) and complementarily (e.g., dog-bone) related concepts. Although
      complementary relations produce more robust priming (e.g., Lupker, 1984),
      categorical responding is more common in preference tasks where participants
      choose directly between categorical and complementary relations (e.g., Smiley &
      Brown, 1979). Three experiments examined the effects of instructions and
      individual differences on adult preferences. Experiment 1 demonstrated that
      category preferences were infrequent, and that "most similar" instructions
      produced modestly more category responses than "goes together" instructions. In
      Experiments 2 and 3, emphasizing key words enhanced the instructional effect, and
      "similar" instructions produced especially large increases in category
      preferences for participants predisposed to categorical relationships. These
      preference experiments demonstrate that complementary advantages are similar to
      those for priming, and that instructions and prior tendencies can have subtle
      influences on semantic memory.

PMID- 9025328
TI  - Inhibition of return along the path of attention.
AB  - Two experiments were conducted to examine inhibition of return (IOR) at four
      potential target locations (a near and a far location in each visual hemifield).
      In the first experiment, the locations were aligned horizontally and IOR was
      found at the near locations when the cues were presented at the far locations but
      not at the far locations when the cues were presented at the near locations. In
      the second experiment, the locations were not horizontally aligned and IOR was
      not found for near locations when the far locations were cued. The results
      suggest that IOR may be an attentional phenomenon and that attention may operate
      in an analog fashion such that locations in the path of the attentional movement
      may be attended to.

PMID- 9025329
TI  - The extension of the interference effect to multiplication.
AB  - Using multiplication facts, this experiment demonstrated an interference effect
      in the number-matching task. Here, subjects verified the presence of a target
      number (e.g., 8) in a previously presented cue (e.g., 5 x 8) that was masked
      after 60 ms. The SOAs between cue and target were 100, 120, 220, and 350 ms.
      Subjects were slower to reject targets that were the product of the cue (e.g.,
      40) than to reject unrelated targets (e.g., 42), but this was true only at the
      100- and 120-ms SOAs (i.e., the interference effect). This pattern is consistent
      with the interference effect found by LeFevre and colleagues using addition
      facts. Furthermore, the present result supports the interpretation that the
      interference effect previously found with addition facts was due to obligatory
      activation and not to automatic counting.

PMID- 9025330
TI  - The roles of stimulus-response compatibility and mental rotation in mirror-image
      and left-right decisions.
AB  - People were shown rotated letters and timed as they decided (a) whether the
      letters were normal or backward, or (b) whether a dot was to the left or right of
      each letter with respect to its upright orientation. In the viewer-centered
      version of (b), the judgement was to be independent of whether the letter was
      normal or backward, so that stimulus-response (S-R) compatibility was confounded
      with angular orientation. In the letter-centered version, the judgement was
      relative to the letter's own coordinates, so that the confounding between S-R
      compatibility and orientation was reversed for backward letters. The functions
      relating RT to angular orientation were parallel across the three tasks,
      suggesting that S-R compatibility played no role, and that the participants
      mentally rotated the letters to the upright in each case. A marked increase in RT
      to backward letters in the letter-centered task suggested a second rotation in
      depth to restore the letters to normal.

PMID- 9025331
TI  - Tapping sensitivity to processing in short-term memory.
AB  - This experiment examines the interference between tapping and searching in short
      term memory (STM). In a concurrent processing condition, the subject first
      memorized a set of digits, and then executed a series of 17 taps separated by 2 s
      subjective time intervals. In each intertap interval, a probe was presented for
      comparison with the items in the memory set. The amount of processing in STM was
      varied from series to series by manipulating the number of items in the memory
      set. The results showed that mean duration and variability of intertap intervals
      increased proportionally with memory set size. This effect is explained by
      interference between processing in STM and the timing component of the tapping
      performance. Tapping sensitivity to memory load suggests that, under some
      conditions, variations in tapping performance are valid indicators of STM
      processing requirements of a concurrent primary task.

PMID- 9025332
TI  - Immediate serial recall, word frequency, item identity and item position.
AB  - Eighteen subjects completed an immediate serial recall task, where the to-be
      recalled lists consisted of either high, medium, or low-frequency items.
      Moreover, lists were either phonologically similar or distinct. Results showed
      that increasing frequency enhanced item information recall but had no effect on
      order recall. Conversely, increasing phonological similarity had a detrimental
      effect on order recall but no significant effect on item recall. It is argued
      that both effects reflect retrieval processes where degraded representations are
      reconstructed on the basis of long-term knowledge: Low-frequency words have
      reduced accessibility, lowering the probability of correct reconstruction, and
      phonologically similar items are more easily confused with other recall
      candidates.

PMID- 9025333
TI  - The small intestine as the origin of bacteremia in acute diffuse peritonitis.
AB  - Studies have demonstrated the failure of gut barrier function in all cases of
      experimental acute diffuse peritonitis. Histobacterioscopy and electron
      microscopy showed the occurrence of bacteria under the basal membrane, in
      lymphatic and blood capillaries of the small intestinal villi. Experimental and
      clinical trials with blood sampling from different regions of the circulation
      have demonstrated the gut origin polymicrobial bacteremia in 66% of patients and
      in 75% of experimental animals with acute diffuse peritonitis.

PMID- 9025334
TI  - Response bias in color priming.
AB  - Four experiments investigated the role of response bias in color priming.
      Subjects were shown three prime-target pair conditions: same color trials,
      category priming trials (in which prime and target were different colors
      associated with the same response category) and incongruent trials. The subjects'
      task ('go-no-go' vs. 'two-choice' RT, Experiments 1-2), the categorization
      criterion of the stimuli (Experiment 3) and the proportion of the same versus
      different response trials (Experiment 4) were manipulated to influence the amount
      of response bias. Overall, the results indicate that color priming is produced
      whether or not a bias is generated at the response level, suggesting that the
      mechanisms underlying the two effects are largely independent of each other.

PMID- 9025335
TI  - The influence of enactment on short-term recognition.
AB  - In three experiments subjects worked on a short-term memory recognition task
      (Sternberg Paradigm) with verbs. In Experiment 1 nouns were used in addition.
      Half of the verbs were encoded by a verbal learning task (VT), and the other half
      by a subject-performed task (SPT). With SPTs, subjects were required to perform
      the actions denoted by the verbs during study. With SPT, in Experiment 1 each
      verb of the memory set was performed and in Experiments 2 and 3 only a single
      verb of each list was performed, making this item unique. All encoding conditions
      showed set-size effects which did not interact with the type of encoding. Even
      response times on the single performed item of the set showed set-size effects,
      comparable in size to the other conditions. SPT did not change the slope of the
      reaction-time function over set size, but when the whole list had been performed
      subjects reacted more slowly in the SPT condition than in the VT condition,
      whereas when a single item was performed this item was recognised faster than the
      non-performed items. We conclude (a) that SPT does not influence memory entries
      in verbal short-term memory, (b) that the set-size effect has its origin in the
      access to the memory entry of the target based on the surface information of the
      words, and (c) that the effect of having performed the item is effective after
      this access to memory.

PMID- 9025336
TI  - Narrow Band Imaging and fluorescence and its role in wound pattern documentation.

PMID- 9025337
TI  - Nursing school a life-shaping experience.

PMID- 9025338
TI  - Ethical awareness in practice.

PMID- 9025339
TI  - Nurse practitioners: stretching the limits of nursing practice.

PMID- 9025341
TI  - Net wise.

PMID- 9025340
TI  - Advanced community nursing practice: Athabasca University meets the challenge of
      primary health care.

PMID- 9025342
TI  - Nursing job file.

PMID- 9025343
TI  - How nurses can deal with depression--a personal story.

PMID- 9025344
TI  - Merge ahead! Nursing and the Internet.

PMID- 9025345
TI  - Nursing job file.

PMID- 9025346
TI  - Laying down the law.

PMID- 9025347
TI  - Continued series: it can happen to you.

PMID- 9025348
TI  - Healthier communities: where are the outcomes?

PMID- 9025349
TI  - True team players needed in management today: "making the team" is just the
      beginning.

PMID- 9025350
TI  - A crisis of self esteem.

PMID- 9025351
TI  - Integrated care approaches and the future of nursing: an oxymoron?

PMID- 9025352
TI  - Caution needed in aged care changes.

PMID- 9025353
TI  - Needle exchanges provide useful data.

PMID- 9025354
TI  - Refugees & torture.

PMID- 9025355
TI  - Evidence based practice. The future is clear.

PMID- 9025356
TI  - Seven steps to research success.

PMID- 9025357
TI  - Mental health nursing and evidence-based practice.

PMID- 9025358
TI  - The research experience.

PMID- 9025360
TI  - Case mix and the big picture.

PMID- 9025359
TI  - Nursing and the law. Coroners as reformers.

PMID- 9025361
TI  - Should euthanasia be legalized in the UK?

PMID- 9025362
TI  - Specialist practitioners: are they all the same?

PMID- 9025363
TI  - Assisting patients to comply with leg ulcer treatments.
AB  - A great deal of work has been done in recent years to highlight and improve the
      leg ulcer problem in the UK. Leg ulcer clinic projects have resulted in effective
      treatments (Moffat, 1990), guidelines to assist in the appropriate management of
      leg ulcers (Nelson, 1996) and leg ulcer clinics that aim to prevent recurrence
      (Ruane-Morris et al, 1995). However, even with the best possible treatment
      strategies based on reliable research evidence, many patients do not comply with
      the recommended treatment and therefore have persistent non-healing or recurrent
      ulceration (Moffat and Franks, 1995). Patient education is vastly important in
      this area and can be supported by education leaflets to facilitate learning.
      Educational theories can also be drawn on to ensure that patient education is
      based on sound evidence.

PMID- 9025364
TI  - Can telephone follow-up improve post-discharge outcomes?
AB  - Much effort and time can be devoted to discharge planning, but what measures
      exist to systematically ensure that everything has gone according to plan, and
      that no unforeseen problems have occurred once the patient has returned home? One
      possible solution evaluated by this study was the routine follow-up of patients
      discharged from a medicine for the elderly ward by telephone. This method was
      found to be quick cheap and effective. It also had the additional benefits of
      offering the opportunity to give further advice, reinforce health education, and
      for some help to provide an emotional bridge between hospital and home.

PMID- 9025365
TI  - Faecal incontinence in adults. 1: Prevalence and causes.
AB  - Faecal incontinence is much more common in the general population than is often
      realized. Recent epidemiological work suggests that over 1% of all adults have
      some degree of faecal leakage. Although the problem increases with advancing age
      and disability, there are large numbers of otherwise healthy adults with this
      distressing symptom. Many, possibly the majority, do not seek professional help.
      The most common causes include childbirth by vaginal delivery, especially if
      assisted with forceps, any condition causing frequency or diarrhoea, and a
      variety of anorectal conditions. A detailed and empathic history taking, physical
      examination, and use of anorectal investigative techniques where indicated,
      enables an accurate individual diagnosis in most cases. A subsequent article will
      explore the treatment and management options once a diagnosis has been reached.

PMID- 9025366
TI  - Consultant nurse: an appropriate title for the advanced nurse practitioner?
AB  - The term 'consultant nurse' has been offered as an appropriate title for the
      'advanced nurse practitioner'. Although both share similar roles and functions
      the way that each will perform within these roles will differ. Many of the
      principles and processes involved in consultancy may be viewed by nurses as
      incongruent with nursing practice, including the relationship between the
      consultant and the consultee and the view that the consultant nurse should not
      have a direct care role. The title itself has medical connotations and therefore
      is viewed negatively by many nurses as it conjures up a view of an aloof, elitist
      practitioner. Nursing is unique, and although many of the processes involved in
      consultancy are appropriate to nursing they should only be used in a way that
      keeps the patient at the centre of care. The title is therefore seen as
      inappropriate for the advanced nurse practitioner.

PMID- 9025367
TI  - Role definition: nurse practitioners or clinicians' assistants?
AB  - This article discusses two different types of nursing role currently being
      developed and highlights their impact on professional practice. One role type is
      concerned with meeting trusts' needs to reduce junior doctors' hours and costs,
      and includes specific aspects of medical practice. The second seeks to advance
      nursing practice and patient care. Both however, lack organization and clarity of
      definition. Developing the first type will not achieve the objectives of the
      second, even if the title of nurse practitioner is attached to the role. The
      nurse surgical assistant provides a lucid example of a role that is being
      medically defined, driven and supervised. Although individual nurses are clearly
      enjoying their new roles, the unique and valued characteristics of nursing are
      being threatened. This retrograde step should be viewed as unacceptable to the
      profession.

PMID- 9025368
TI  - Piloting an A&E and practice nurse educational exchange.
AB  - The accident and emergency (A&E) department acts as an interface between primary
      and secondary care. Traditionally, general practice has been viewed negatively by
      A&E nurses. This article explores some of the issues surrounding these views. The
      need to challenge the traditional view of A&E as simply a department within a
      hospital and replace it by one that identifies A&E within the broader community
      context is identified. This change in ethos requires nurses who work in the A&E
      department to challenge their beliefs about the specialty. There is a need to
      look at the educational preparation of A&E nurses. A pilot educational exchange
      scheme, developed to explore ways of improving the relationship between A&E
      nurses and nurses working in general practice, is described.

PMID- 9025369
TI  - A practical framework for wound assessment. 1: Physiology.
AB  - Wound assessment offers practitioners a framework upon which to base clinical
      decisions aimed at maximizing healing potential. It relies heavily on basic
      observational skills to detect often subtle differences between a healing and non
      healing wound and focuses on the difficulties in identifying clinical signs of
      wound infection. Part one of this paper relates the physiological process of
      healing to the practical skill of wound assessment so that appropriate management
      objectives can be implemented and evaluated. In the second part, wound
      classification models are reviewed, together with practical methods of wound
      measurement and suggestions for improving the quality of wound management
      documentation.

PMID- 9025370
TI  - Community mental health teams: development in community care.
AB  - This article discusses research undertaken in an area of South Wales on the
      functioning of community mental health teams, which took place during the closure
      of two large psychiatric hospitals and the development of the Welsh Office
      strategy for mental illness. Key findings relate to the lack of clarity of the
      role of team coordinators, the absence of individual performance review systems,
      the diversities in referral systems and caseloads. An attempt was made to develop
      a performance matrix in relation to individual teams.

PMID- 9025371
TI  - Encouraging team collaboration in healthcare.

PMID- 9025372
TI  - Differentiated practice in Colorado--what's happening?

PMID- 9025373
TI  - Trends in smoking cessation.

PMID- 9025375
TI  - A corporate approach to healthcare ethics.

PMID- 9025374
TI  - Where do you stand in delivering quality customer service?

PMID- 9025376
TI  - Denver HIV/AIDS demonstration program--project SNAPP is a winner!

PMID- 9025377
TI  - On your own--the nurse entrepreneur.

PMID- 9025381
TI  - Pain: real or imagined?

PMID- 9025382
TI  - Theory based nursing practice in pain management.

PMID- 9025383
TI  - Pain management progressing.

PMID- 9025384
TI  - The promise of nursing in managed care.

PMID- 9025385
TI  - The business of healthcare.

PMID- 9025386
TI  - Nurse-managed community healthcare for seniors. Interview by Marie Manthey.

PMID- 9025387
TI  - The primary nurse and the case manager in managed care.

PMID- 9025388
TI  - Risk management: implications for nurses.

PMID- 9025389
TI  - Continuing education: seeking quality programs.

PMID- 9025390
TI  - The safe and effective handling of glutaraldehyde solutions. Society of
      Gastroenterology Nurses and Associates, Inc.
AB  - Glutaraldehyde remains the most widely used method of providing high-level
      disinfection in healthcare settings. It is imperative that healthcare workers use
      glutaraldehyde properly and take the correct precautions. It is the
      responsibility of everyone working with glutaraldehyde to ensure his/her own
      safety as well as that of co-workers. This monograph outlines the goals of proper
      use and provides a reference for appropriate protection ensuring safe use.

PMID- 9025391
TI  - Caring for ourselves ... and each other.

PMID- 9025392
TI  - A quality assurance monitor on preparation for outpatient lower endoscopic
      procedures.
AB  - A two-phase quality assurance monitor was performed with a pediatric outpatient
      population to determine how well the current preparation of Fleet Phospho-Soda,
      Fleet enemas, and diet modification cleaned the colon. We studied 99 patients in
      Phase 1, implemented changes, and then studied 99 patients in Phase 2. Phase 2
      found increasing age to be significantly related to decreasing cleanliness of the
      transverse colon, ascending colon, and cecum, and increasing weight was found to
      be significantly related to decreasing cleanliness of the cecum. Phase 2 also
      found the second enema to be significant for increasing cleanliness of the
      rectum.

PMID- 9025393
TI  - Practical computer applications for endoscopy.
AB  - A computer can facilitate a nurse's administrative tasks, resulting in increased
      time to spend with patients. Data can easily be organized and retrieved. Forms
      can be created when there is no ready-made form at hand. Document revision is
      easy and cost-effective because the form is not typeset until it has been tried
      and is ready for permanent adoption. The outcome will be a nursing practice that
      is more efficient, effective, and professionally rewarding.

PMID- 9025394
TI  - Enema administration techniques used by experienced registered nurses.
AB  - The enema has evolved through trial and error, not scientific investigation.
      Because little scientific base exists, the authors began their study of enemas by
      examining current nursing practice. They asked 24 experienced registered nurses
      to describe how they give enemas, and if they had seen any complications.
      Interviews were audiotaped, transcribed, and analyzed using qualitative analysis
      software. The authors found that the nurses emphasized patient cooperation,
      preparation, and comfort; had observed few complications, and had difficulty
      describing quantitative aspects of enemas (e.g., amount of solution given, speed
      of administration).

PMID- 9025395
TI  - Evaluation of the safety of nurse-assisted percutaneous endoscopic gastrostomy.
AB  - Percutaneous endoscopic gastrostomy (PEG) procedures have become a common,
      nonsurgical approach to providing enteral access to patients who are otherwise
      unable to meet their nutritional needs by mouth. Historically, two physicians
      have been required to complete this procedure; the first performed the endoscopy
      while the second helped to position the PEG tube. As a result of constraints on
      physicians' time and availability, as well as increased medical costs, this
      process has changed in some settings where the procedure is accomplished by one
      physician who performs the endoscopy and directly observes a nurse who acts in
      the role of the second physician. This research study was designed to evaluate
      the safety of nurse-assisted PEG procedures by comparing the complications of
      placement (i.e., infection, hemorrhage, perforation, and ileus) with those
      complications that occur when two physicians perform the procedure. The current
      standard of care for placing PEG tube was followed. Results in this small sample
      show that nurse-assisted PEG procedures are as safe as when two physicians
      perform this procedure.

PMID- 9025396
TI  - Last wish.

PMID- 9025397
TI  - Moctanin.

PMID- 9025398
TI  - Recovery time and safe discharge of endoscopy patients after conscious sedation.
AB  - The aim of this study was to identify the best method for determining when to
      safely discharge the endoscopy patient; specifically, it was designed to
      determine whether the patient's risk factors, intraoperative occurrences, and/or
      medications used during endoscopy should be used to determine the minimum length
      of stay postconscious sedation or whether a general policy can be used, as is
      currently practiced at many institutions. Preoperative, intraoperative, and
      postoperative data were collected on a convenience sample of 405 adult ambulatory
      outpatients undergoing upper endoscopy and/or colonoscopy. Subjects were also
      interviewed by phone within 48 hours of discharge to assess postdischarge
      complications and their duration. Age predicted length of time in recovery, but
      only 2% of the variation in recovery time was predicted by the study variables.
      Intraprocedure occurrences predicted postprocedure occurrence. The implications
      of these and other findings are discussed in relation to nursing practice and
      future research.

PMID- 9025399
TI  - Improving nursing practice with staff education: the challenges of dysphagia.
AB  - The 15 million Americans who experience some degree of dysphagia risk choking,
      airway obstruction, aspiration-related pulmonary disease, and/or death. These
      complications increase mortality, morbidity, length of hospitalization, and
      healthcare costs, but may be preventable through nursing intervention. Fifty-four
      nursing care workers (NCWs) from medical/surgical units in two acute care
      hospitals were assigned by convenience to two experimental groups and a control
      group. Experimental groups A and B participated in an educational program on
      dysphagia designed to increase their knowledge of dysphagia, knowledge attention,
      and the number of dysphagic patients identified and referred. Group B received
      deliberate reinforcement of program content over a 1-month period. The
      educational intervention had a significant effect on knowledge level and
      knowledge retention, immediately and at 1-month posttest in both experimental
      groups. NCWs applied what they learned to clinical practice as evidenced by an
      increase in the number of patients identified as being at risk for or
      experiencing dysphagia. Reinforcement of program content did not affect the
      outcomes. The study has implications for staff educators and nursing personnel
      who care for persons at risk for dysphagia.

PMID- 9025400
TI  - Total parenteral nutrition (TPN) at home: prototype high-tech home care nursing.
AB  - Current economic and demographic trends in the United States indicate the demand
      for complex treatments, such as infusion therapies at home, will continue to
      escalate. In light of the increasingly acute and autonomous nature of home health
      practice, examination of home care nursing process affecting patient care
      outcomes is crucial. This study explored the cognitive, technical, and
      interpersonal components included in total parenteral nutrition (TPN) home care
      nursing. The purpose of this study was to evaluate psychometrically the Schmele
      Instrument to Measure the Process of Nursing Practice in Home Health (SIMP-H) so
      that it may be used to examine high-tech home care nursing process. Home visits
      must be observed to identify the specific cognitive, technical, and interpersonal
      components included in high-tech home care nursing that are important for patient
      care outcomes. This study captured high-tech home care nursing process on
      videotape, which provided a medium for evaluating interobserver reliability for
      the SIMP-H. Results revealed an interobserver reliability coefficient of .72.

PMID- 9025402
TI  - Position statement: role delineation of the advanced practice nurse in
      gastroenterology/hepatology and endoscopy. The Society of Gastroenterology Nurses
      and Associates, Inc.

PMID- 9025401
TI  - Society of Gastroenterology Nurses and Associates, Inc. (SGNA) Endoscopic
      Disinfectant Survey results compared with control group.
AB  - Disinfectant surveys from responding members of the American Society of
      Postanesthesia Nurses were divided into two groups based on whether or not they
      considered themselves to be exposed to disinfectants in their work environment.
      Their survey responses were then compared with those obtained previously from
      members of the Society of Gastroenterology Nurses and Associates, Inc., who were
      regularly exposed to 2% alkaline glutaraldehyde in the work setting. There were
      significant differences among the groups in the percentage of respondents who
      reported having headaches, eye irritations, respiratory problems, shortness of
      breath, rashes, memory loss, mood swings, and fatigue. These findings support the
      association of these complaints with 2% alkaline glutaraldehyde exposure. In
      contrast, there were no significant differences among the groups in the
      percentage of respondents who reported having asthma, rhinitis, chest pain,
      nausea, diarrhea, muscle/joint pain, visual disturbances, or dermatitis.

PMID- 9025403
TI  - Active listening.

PMID- 9025405
TI  - Nursing education for the future.

PMID- 9025406
TI  - Operating in the context.

PMID- 9025404
TI  - Common vitamin B complex agents and folic acid: Part I. Cyanocobalamin (vitamin
      B12) (kaybovite [parenteral]; berubigen; betalin-12; kaybovite-1000; rubramin
      pc).

PMID- 9025407
TI  - Domains of learning: interdependent components of achievable learning outcomes.
AB  - "Domains of learning" refers to the three separate, yet interdependent components
      of learning outcomes achievable by human learners. These domains--cognitive,
      affective, and psychomotor-represent various categories and levels of learning
      complexity and are commonly referred to as educational taxonomies. The cognitive
      domain refers to knowledge attainment and mental/intellectual processes. The
      affective domain characterizes the emotional arena reflected by learners'
      beliefs, values and interests. The psychomotor domain reflects learning behavior
      achieved through neuromuscular motor activities. Educators use the domains to
      assist in determination of learning objectives essential to planning,
      implementing and evaluating teaching-learning processes and outcomes of human
      learners across the life span. Actual instances of domain use from programs,
      interviews and the literature complement the theoretical notions presented in
      this article.

PMID- 9025408
TI  - Reflective learning: work groups as learning groups.
AB  - Staff development educators are challenged to develop additional learning
      strategies to meet the demands of the professional nurse in the changing
      healthcare environment today. Methodology for workplace learning is being
      developed to meet the critical thinking skills necessary for the professional
      nurse of the future. This article identifies the use of reflective learning in
      the workplace and reports outcomes from the implementation of the reflection-on
      action technique. The implications for staff development educators are reviewed
      for the concept of work groups as learning groups.

PMID- 9025409
TI  - Critical Path education: necessary components and effective strategies.
AB  - Proper use of Critical Paths based on a solid educational foundation aids
      caregivers in meeting the ultimate challenge of today's healthcare environment:
      to provide a higher quality of care at a lower cost. The components for a
      comprehensive educational program for Critical Paths include general principles,
      Path contents, Path development, guidelines for documentation, variance data
      collection and evaluation. A strategy to provide large numbers of staff with
      background information is through the use of self-learning packets; the case
      study approach is an appropriate strategy for Path specific education. Evaluation
      data indicate that both strategies are effective in assisting staff to develop
      and implement Critical Paths.

PMID- 9025410
TI  - Preceptorships in high-risk perinatal nursing for rural nurses: a pilot project.
AB  - A need existed in New Mexico to enhance the skills of nurses in rural areas in
      the management of high-risk perinatal patients. However, barriers prohibited
      initiating such a program, including: a) program development and approval; b)
      legal and insurance issues; c) determining financial responsibility; and d)
      application and selection process. Resolving these problems came in the form of a
      collaborative effort among three departments at the University of New Mexico. A
      preceptor program of clinical and classroom experiences was developed for nurses
      outside of the Albuquerque metropolitan area. Evaluations of the program at six
      months revealed that program participants had implemented changes in their
      nursing practice. Revisions of the program and plans for the future are
      discussed.

PMID- 9025411
TI  - Psychometric evaluation of the Program Evaluation Instrument.
AB  - Most continuing education program evaluations are developed informally with
      little attention paid to psychometric properties. Rigorous evaluation of
      continuing education programs should measure quality and allow valid comparisons
      across programs. The Program Evaluation Instrument (PEI), which evaluates
      continuing education programs, was tested in this study to further evaluate its
      psychometric properties. The 19-item instrument consists of four theoretical
      subscales: program objectives, learner objectives, teacher behavior, and program
      satisfaction. Participants (N = 566) completed the instrument after a variety of
      hospital continuing education programs. Principal components factor analysis with
      Varimax rotation revealed two interpretable factors, Preparation and
      Presentation, and Usefulness. Coefficient alphas for the two factors were .94 and
      .70 respectively. The findings suggest item revision and further psychometric
      evaluation.

PMID- 9025412
TI  - Defining home health care nursing: implications for continuing nursing education.
AB  - The purpose of this qualitative interpretivist study was to analyze and
      articulate the characteristics of nursing practice in the home health care
      context. Researchers sought to describe expert home health care nursing practice
      and how it developed. Twenty-one nurses, at various stages of practice
      development, were asked to write three clinical narratives describing their home
      health care practice. Data were analyzed to elicit themes and characteristics of
      nursing practice in the home health care context. Findings indicate that in the
      context of home health care, expert nursing practice develops along a continuum,
      until nurses can integrate physiological data with environmental and family data
      to provide seamless, intuitive, and highly complex nursing care. The results of
      this research can assist continuing education and staff development providers as
      they develop educational programs designed to facilitate professional development
      of new graduates and newly employed nurses in home health care.

PMID- 9025413
TI  - Continuing education: the changing dynamics.

PMID- 9025414
TI  - Changes in leadership styles as a function of a four-day leadership training
      institute for nurse managers: a perspective on continuing education program
      evaluation.
AB  - This study measured changes in knowledge acquisition and application of the
      Hersey and Blanchard model of leadership styles and leadership style adaptability
      among 144 registered nurses who participated in a four-day management institute.
      A pre- and post-institute administration of the LEAD-Self instrument was
      conducted. Although the findings demonstrated a significant change in the
      participants' leadership styles, the data revealed that outcomes were not as
      positive as had been assumed based on participants' self-reports. The discussion
      of findings reveals the complexity and the necessity of measuring learning
      outcomes for continuing education program improvement.

PMID- 9025416
TI  - 21 predictions for the future of hospital staff development.
AB  - No one knows for sure how the future will look. However, there is no better time
      than today to begin envisioning and creating our preferred future. This article
      discusses several factors that will impact the future of nursing staff
      development. Twenty-one predictions are offered that include: change,
      restructuring, teamwork, leadership development, paradigms, support networks,
      staff development roles, learning, value of life experiences, patient education,
      cultural diversity, and technology. Strategies for educators to position
      themselves for the future are suggested. The future is ours to create. The intent
      of this manuscript is to challenge staff development educators to create visions
      and develop strategies to construct the preferred future of their roles and the
      nursing staff development function.

PMID- 9025415
TI  - Community-based educational programs for cancer nursing.
AB  - A United Way grant allowed the Department of Nursing Research and Education to
      make available its expertise in cancer nursing and establish itself as a resource
      for oncology. Community educational needs were assessed by a questionnaire sent
      to outside agencies prior to designing an oncology educational program. In a 9
      month period, 57 classes at 21 different facilities representing 417 hours of
      instruction were provided. Nurses attending the classes totaled 1,175. Results
      showed an increase in scores from pre-test to post-test, indicating that
      participants demonstrated increased knowledge as a result of class participation.
      This funding provided the catalyst to prepare a large number of community
      hospital nurses in the complex care of oncology patients.

PMID- 9025417
TI  - A continuing education program to retrain registered nurses for careers in client
      focused community healthcare.
AB  - The purpose of the grant-funded program was to address educational needs arising
      from the changing role of registered nurses in the delivery of healthcare because
      of shifts occurring from acute hospital-based care to primary care community
      based services. The grant contributed the financial resources necessary to
      provide administrative support, develop the curriculum and teach the content.
      Taught jointly by nurse educators and community-based practitioners, the program
      provided 99 hours of classroom/college laboratory instruction and 96 hours of
      community-based clinical experiences flexibly structured to meet the needs of
      working nurses. It provided training at two educational sites for over 40
      registered nurses who were unemployed, working in acute care and looking to cross
      over to community-based settings, or already in a community setting yet
      interested in sharpening their skills. Nurses were able to earn college credit or
      continuing education units (CEUs) for successful completion of the program.

PMID- 9025418
TI  - Wanted: "A few good bug detectives". A gaming technique to increase staff
      awareness of current infection control practices.

PMID- 9025420
TI  - Adult nipple confusion: a commerciogenic problem.

PMID- 9025419
TI  - Who publishes and where they publish.

PMID- 9025422
TI  - Artificial baby milk companies: education or marketing?

PMID- 9025421
TI  - Encourage mothers to promote breastfeeding.

PMID- 9025423
TI  - Insufficient prolactin: unsupported and unlikely.

PMID- 9025424
TI  - Where can mothers donate excess milk?

PMID- 9025425
TI  - Standing feeding orders in a well-baby nursery: "water, water everywhere...".
AB  - The objective of this study was to examine standing physician orders affecting
      healthy breastfeeding newborns for items not in concert with the "Ten Steps to
      Successful Breast-feeding." All order sets of physicians or physician groups (n =
      22) at a mid-sized hospital in central New Jersey (USA) (approximately 1200
      deliveries/year) were reviewed. Seventeen orders called for water to be offered
      routinely as the first feeding. Five order sets called for two or more such
      feeds. Twelve orders gave infants nothing by mouth (NPO) for more than 2 hours
      and six mandated 4-hour intervals between feedings. Practices that undermine
      successful breastfeeding are still ubiquitous. Physician orders, in addition to
      hospital policy, should be targeted for improvement.

PMID- 9025427
TI  - Social status, mother-infant time together, and breastfeeding duration.
AB  - Chart review and direct observation were used to study the relationship between
      social status, mother-infant time together, and breastfeeding duration among 138
      mothers who were breastfeeding at hospital discharge. Overall breastfeeding rate
      was 73 percent for patients with private insurance and 37 percent for patients
      without private insurance. Breastfeeding duration to six months was not related
      to social status. Mother-infant time together from birth through 48 hours was 3
      hours greater for private insurance mothers. These three hours, which were
      statistically significantly different, did not correlate with breastfeeding
      duration in any way. Ancillary findings were that married mothers were more
      likely that unmarried mothers to be breastfeeding at six months, and that mothers
      who received epidurals were less likely to be breastfeeding at six months than
      mothers who did not receive epidurals.

PMID- 9025426
TI  - The effect of sequential and simultaneous breast pumping on milk volume and
      prolactin levels: a pilot study.
AB  - Mothers who must express milk for a prolonged period frequently report that milk
      volumes decrease. The purpose of this pilot study was to assess the feasibility
      of having a sample of lactating mothers of preterm infants follow a specific
      breast pumping protocol, express milk mechanically for six weeks, and have a
      subsample consent to venipuncture. This pilot study compared the effects of
      pumping breasts sequentially or simultaneously on milk volume and prolactin
      levels in mothers of preterm infants. Nine lactating mothers were randomly
      assigned to a sequential single or simultaneous double electric breast pumping
      system. Prolactin levels were examined in four mothers on days 21 and 42
      postpartum. The sequential single and simultaneous double groups had mean
      baseline prolactin levels of 50.8 ng/ml and 40.6 ng/ml, respectively on day 21,
      and 26.6 ng/ml and 34.5 ng/ml, respectively, on day 42 postpartum. At 9 and 12
      weeks postpartum mothers were queried about their lactational status. The results
      suggested that milk yield may be maintained or increased with frequent use of the
      simultaneous double pumping system. Further study is needed to confirm results of
      this pilot study.

PMID- 9025428
TI  - Development of the Preterm Infant Breastfeeding Behavior Scale (PIBBS): a study
      of nurse-mother agreement.
AB  - Research on the development of preterm infant feeding behavior has focused mainly
      on bottlefeeding, using invasive methods or observations by professionals. In
      this study, a clinical method for observing breastfeeding was developed in
      collaboration between observers and mothers for the purpose of enabling neonatal
      personnel and mothers to describe developmental stages in preterm infant
      breastfeeding behavior. Tests of interobserver reliability resulted in acceptable
      agreement between observers, but a somewhat lower level of agreement between
      observers and mothers. The scale showed a good capacity to discriminate between
      infant gestational ages and can be used for helping mothers to identify their
      infants' emerging competence.

PMID- 9025429
TI  - Supporting a preterm infant's behaviour during breastfeeding: a case report.
AB  - Preterm infants present a special challenge to lactation consultants because of
      their high reactivity to stimuli from their physical and social environment, low
      muscle tone, and limited extent of awake, alert behavior. In a descriptive case
      report, a girl at an age corresponding to a gestational age of 29 weeks was
      observed during a breastfeeding session according to the Newborn Individualized
      Developmental Care and Assessment Program (NIDCAP). Recommendations, based on her
      behavioral responses, were given to her mother. In an observation two days later,
      she showed more wakefulness and more efficient sucking. General recommendations
      are offered for support of preterm infants' behavior during breastfeeding. The
      NIDCAP structure is advocated as a mental checklist for breastfeeding assessment
      and advice.

PMID- 9025430
TI  - Developing a frenotomy policy at one medical center: a case study approach.
AB  - The objective of this study was to change procedures in our medical center
      regarding frenotomy for ankyloglossia (tongue-tie). The medical and breastfeeding
      outcomes of 36 fullterm infants who received frenotomies were studied. The
      information was used to develop frenotomy eligibility standards that would guide
      other physicians and insure timely treatment to avoid breastfeeding cessation.

PMID- 9025431
TI  - Relactation in a newborn intensive care setting.
AB  - A woman who did not initiate breastfeeding after the birth of her preterm infant
      did so 27 days later, after her infant developed necrotizing enterocolitis. Using
      specific strategies including kangaroo care principles and simultaneous breast
      pumping to facilitate relactation, the mother was able to provide an adequate
      supply of breastmilk at the time of her infant's hospital discharge.

PMID- 9025432
TI  - A standing order for in-hospital lactation consultation.
AB  - Written criteria for referral can clarify the circumstances in which the services
      of a lactation consultant could benefit postpartum hospital patients. These
      criteria are identified as a component of a hospital's "Standards of Care for
      Breastfeeding Families."

PMID- 9025433
TI  - European drug information centers.
AB  - Drug information is a clinical specialty throughout the United States and Europe.
      This professional support service not only addresses drug information requests,
      but also provides pharmacy (drug) and therapeutics support, newsletter
      publication, fee-for-service consultation, education, drug policy development,
      and research. Although the primary services of drug information centers (DICs) in
      Europe are similar to those in the United States, substantial differences have
      been reported. Recent surveys have compared the locations, resources, staff, and
      services of the DICs throughout Europe. DICs in the United States and Europe play
      a pivotal role in the provision of pharmaceutical care to patients as well as
      providing support to hospital functions.

PMID- 9025434
TI  - Organization and activity of a Human Milk Bank in Poland.

PMID- 9025435
TI  - Practical talks to midwives on the care of mother and infant. 1930.

PMID- 9025436
TI  - ILCA: the past, the present, the future.

PMID- 9025437
TI  - Are we creating our own breastfeeding mythology?

PMID- 9025438
TI  - Expressing ourselves: breast pumps.

PMID- 9025439
TI  - "Certification" for a program vs. certification through board examination
      achievement.

PMID- 9025440
TI  - Identifying baby-friendly restaurants: a win-win situation for mothers, babies,
      and eateries!

PMID- 9025441
TI  - Prolonged breastfeeding and dental caries.

PMID- 9025442
TI  - Clinical use of silicone nipple shields.
AB  - Use of nipple shields is controversial. However, when weaning is imminent, they
      may enable breast-refusing infants to transfer back to the breast. A chart review
      of 248 clients seen during a 13-month period in a private lactation clinic
      revealed 32 women who received thin, silicone nipple shields. Among this group,
      the most common presenting problems were breast refusal (69 percent) and
      difficulty with latch (25 percent). Bottles had been introduced in 75 percent of
      these cases. Thirty-eight percent of the mothers using nipple shields weaned
      their infants during the initial crisis period; 56 percent continued to
      breastfeed for at least six weeks postpartum. Two ill infants continued to
      receive human milk by bottle for four and 12 months respectively. Parity appeared
      to correspond inversely with success of the shield intervention. The presence of
      flat or inverted nipples appeared to contribute to the phenomenon described as
      "nipple confusion."

PMID- 9025443
TI  - Use of a silicone nipple shield with premature infants.
AB  - Nipple shields have been used with premature infants to facilitate breastfeeding
      in certain circumstances. In this paper, clinical observations and chart reviews
      regarding nipple shield use by 15 premature infants are reported. Volume taken at
      the first breastfeeding was compared to the volume prescribed by the physician,
      based on caloric requirements for infant weight. Using test weights, we found
      that 60 percent of these infants consumed 50 percent or more of the prescribed
      amount with the first use of the nipple shield. The nipple shield was found to be
      useful in certain circumstances where mothers had attempted breastfeeding
      previously.

PMID- 9025444
TI  - Mothers' reports of the outcome of nipple shield use.
AB  - Although nipple shields have undergone significant design improvements in recent
      years, many lactation consultants are reluctant to use them to assist with
      breastfeeding challenges. This article shares the experience of lactation
      consultants and their clients in the Breastfeeding Center at Evergreen Hospital
      with the use of ultrathin, silicone nipple shields. Fifty-one clients who used
      ultra-thin nipple shields were interviewed by telephone to determine patterns of
      use and client satisfaction. Eighty-six percent of the respondents reported that
      the ultra-thin nipple shield helped them continue to breastfeed. Our positive
      experiences, along with those of our clients, suggest that ultra-thin nipple
      shields can be a useful lactation tool in maintaining the breastfeeding
      relationship until problems are resolved.

PMID- 9025445
TI  - Rethinking the use of nipple shields.

PMID- 9025446
TI  - Long-term nipple shield use--a positive perspective.
AB  - This report describes ten cases in which silicone nipple shields were used for
      two weeks or longer. In nine of the cases, shields were used to help babies
      attach to the breast. These babies had struggled to attach to the areola because
      of suck problems or the mother's lack of protractility of breast tissue. In the
      tenth case, the shield was used because of extreme nipple soreness. All babies
      were off the shield by 3.5 months of age; nine were feeding directly from the
      breast. All weights were appropriate or above for the age of the infant at three
      weeks, two months and four months.

PMID- 9025447
TI  - Transitioning to the breast at six weeks: use of a nipple shield.
AB  - After forceful help with breastfeeding on the first day after birth, a baby began
      to refuse to latch onto the breast. The mother received help maintaining her milk
      supply and advice on feeding methods and use of a nipple shield from a lactation
      consultant after leaving the hospital and was eventually able to breastfeed with
      the help of a nipple shield. Important aspects of this case were the treatment in
      the hospital, which included forcing the baby to the breast and using a tube
      feeding device with artificial baby milk. Also critical was this mother's
      commitment to breastfeeding and the long-term support she received.

PMID- 9025448
TI  - Using a silicone nipple shield to assist a baby unable to latch.
AB  - This report describes how use of a nipple shield helped to establish
      breastfeeding when a baby was unable to latch onto the breast. Some of the risks
      associated with nipple shield use are highlighted.

PMID- 9025449
TI  - Hormonal contraception and lactation.
AB  - Hormonal contraceptive measures can be used immediately postpartum if the patient
      so desires. Progestin-only contraceptives are preferable to estrogen-containing
      methods if initiated during the first six months after delivery. Progestin only
      contraceptives do not appear to affect milk volume, composition, or to cause
      deleterious effects in the infant. Ideally for women who desire a form of
      contraception in addition to lactation-induced amenorrhea, progestin-only methods
      should be started at six weeks postpartum if the woman is fully breastfeeding.
      Since contraception protection is provided by lactation amenorrhea, the six week
      delay will decrease infant exposure to exogenous hormones and decrease the
      incidence of irregular postpartum bleeding. Milk volume may decrease with the use
      of estrogen; however, no detrimental effects have been shown on infant growth or
      development. For women who are planning to gradually wean their infant, use of
      COCs may provide an easier transition to bottle-feeding. COCs should be used with
      caution by women who are not able to obtain supplemental milk. A decrease in milk
      volume can lead to earlier discontinuation of the hormonal contraceptive in an
      attempt to increase milk quantity. Supplementation is often needed, and then the
      woman ovulates again, possibly resulting in an unintended pregnancy. Many women
      are motivated immediately postpartum to accept contraception. For other women,
      lack of access to health care may provide barriers in obtaining adequate
      contraception later. In either case, there are adequate data to show no
      detriments of starting progestin-only contraceptives within days of delivery.
      Therefore, the best method for the patient should be employed to ensure adequate
      contraception while preserving optimal lactation.

PMID- 9025450
TI  - Donor milk banking in China: the ultimate step in becoming baby friendly.
AB  - Milk banking is alive and well in China in small in-house milk banks in Baby
      Friendly Hospitals, especially those where staff has had little contact with
      western medical training. Donor milk banking is a logical extension of Step 6 of
      the Baby Friendly Hospital Initiative and is a good indicator of a hospital's
      respect for breastfeeding and its understanding of the unique components of human
      milk.

PMID- 9025451
TI  - The standard medical instructors for the people concerning life, health and
      vitality. 1906.

PMID- 9025453
TI  - Health department steps toward a baby-friendly community.

PMID- 9025452
TI  - A complete treatise on midwifery: the theory and practice of tokology. 1852.

PMID- 9025454
TI  - Code of Ethics for International Board Certified Lactation Consultants.
      International Board of Lactation Consultant Examiners.

PMID- 9025455
TI  - Have you been an advocate today? Your voice counts!

PMID- 9025456
TI  - The obese trauma patient: treatment strategies.
AB  - Despite numerous unique features in the responses to trauma among obese and
      morbidly obese patients, very little literature exists on the care of the injured
      obese person. Factors such as body composition, psychosocial factors, coexisting
      illness, size, and weight necessitate modifications to treatment protocols in
      almost all aspects of trauma care. Adaptations in hygiene, pharmacologic
      management, pulmonary support, rehabilitation, prevention of complications, and
      injury detection are needed to provide effective care to injured obese people.
      Body habitus, technical limitations of equipment, and unique injury patterns may
      increase the risk of missed injuries in this population. This article reviews the
      needs of the obese trauma patient and recommends strategies for effective
      multidisciplinary care.

PMID- 9025457
TI  - Spine clearance--a trauma center's standardized approach to assist care givers.
AB  - Spine clearance is a high-volume, high-risk issue for trauma centers. Spinal cord
      injuries can be one of the most devastating injuries a person can incur. The
      initial treatment regimen can affect the occurrence of permanent injury. Pre
      hospital providers take great pains to immobilize the spine. This article
      describes an approach adopted by a Level I trauma center to manage admitted
      patients where a spinal column or ligamentous injury has not been determined.

PMID- 9025458
TI  - The top 10 Abbreviated Injury Scale (AIS) coding faux pas.

PMID- 9025459
TI  - Will nurses be the conscience of healthcare reform?

PMID- 9025460
TI  - The use of early enteral nutrition in abdominal trauma.
AB  - Patients who sustain abdominal trauma become hypermetabolic and require
      aggressive utilization of early enteral nutrition. The purpose of this article is
      to discuss the physiology of the gut as it relates to the development of septic
      sequelae and the role of early enteral nutrition in decreasing septic
      complications based upon the findings of previously published research. The
      research clearly supports that there are many benefits associated with the
      initiation of early enteral nutrition in this patient population.

PMID- 9025461
TI  - A hope and hopelessness model applied to the family of multitrauma injury
      patient.
AB  - A hope and hopelessness model is applied to the family of multitrauma injury
      patient. The purpose of the article is to identify factors contributing to
      hopelessness and organize them into physiological, cognitive-temporal, affective
      contextual, and affiliative-behavioral hopelessness. Personal experience with
      family's of multitrauma injury patients and research regarding hope,
      hopelessness, and family led to the development of a hope model. Nursing
      interventions are then delineated according to a hope model, which fosters the
      family's sense of hope in themselves and the patient's future. Assessment of
      factors contributing to hopelessness and utilization of the hope model will
      enable nurses and family members to combine their efforts in reducing
      hopelessness and facilitate a sense of hope.

PMID- 9025462
TI  - Sharing our best. A trauma quality improvement flowchart.

PMID- 9025463
TI  - The powerful punch of nicotine: a smoking cessation facilitator's account.

PMID- 9025464
TI  - Smoking cessation: educating for the nursing role.

PMID- 9025465
TI  - [Interference with the genome].

PMID- 9025466
TI  - [Nursing care during generalized tonic-clonic seizures].

PMID- 9025467
TI  - [Results of the use of a new suction catheter--AirVent].

PMID- 9025468
TI  - [Violent situations in everyday nursing--a guide].

PMID- 9025469
TI  - [Nursing personnel should be sensitized. Education in rheumatology helps to deal
      with disease, pain and general problems of life].

PMID- 9025470
TI  - [Periodical blood sugar control].

PMID- 9025471
TI  - [Intramuscular injections from a legislative viewpoint: patients' expressions of
      pain].

PMID- 9025472
TI  - [When triplets have a bath].

PMID- 9025473
TI  - [What does a grief pedagogue do?].

PMID- 9025476
TI  - Fighting domestic violence: a moral imperative of the nursing profession.

PMID- 9025477
TI  - Practice guidelines.

PMID- 9025478
TI  - Reprocessing medical devices sparks ongoing debate.

PMID- 9025479
TI  - Incident reports revisited: focus on the medical device reporting system.

PMID- 9025481
TI  - Revised ANSI standard shifts responsibility.

PMID- 9025480
TI  - Laparoscopic cases common target of malpractice suits.

PMID- 9025482
TI  - The Network Link. An interview with Louise Pasaka, R.N., B.S.N., C.N.O.R.,
      R.N.F.A. Professional nursing seminars Taos Ski Valley, NM.

PMID- 9025483
TI  - Surgical lasers: a technology review.

PMID- 9025484
TI  - Implementation of robotics in the operating room.

PMID- 9025485
TI  - The successful use of the Photoderm VL in the treatment of a cavernous hemangioma
      in a dark-skinned infant.

PMID- 9025486
TI  - Photodynamic therapy: a guide to instrumentation and dosimetry calculations.

PMID- 9025487
TI  - Clinical exemplar.

PMID- 9025489
TI  - Change--an enigma.

PMID- 9025488
TI  - Developing an ethic which responds to people.

PMID- 9025490
TI  - Money or morals?

PMID- 9025491
TI  - A brief overview of the new FDA guidelines.

PMID- 9025492
TI  - The FDA guidelines for water treatment equipment: its impact on the renal
      community.

PMID- 9025493
TI  - Outcomes management: an interdisciplinary approach to improving patient outcomes.

PMID- 9025494
TI  - Trying to measure quality? Ask the patient.

PMID- 9025495
TI  - Transplant patients celebrate life.

PMID- 9025496
TI  - Issues in transplantation. Study: hospitals can do more to increase organ
      donation.

PMID- 9025497
TI  - Accentuate the positive: a critique of the Ad Council campaign to promote organ
      and tissue donation.

PMID- 9025498
TI  - Beginnings of dialysis still in practice in Russia.

PMID- 9025499
TI  - CDC puzzled over neurological disorders at Ala. dialysis unit. Impact of dialyzer
      age questioned.

PMID- 9025500
TI  - How DOQI could be different. Interview by Diane M Goetz.

PMID- 9025502
TI  - Challenges facing the organ procurement community.

PMID- 9025501
TI  - Five markers to help identify malnutrition.

PMID- 9025503
TI  - Outcomes management: an interdisciplinary approach to improving patient outcomes.
AB  - Outcomes management provides a means for interdisciplinary collaboration in
      improving patient outcomes. The benefits of an outcomes management program are
      numerous, including decreasing healthcare costs, decreasing the length of stay,
      improving clinical outcomes, improving system processes, and fostering outcomes
      research. The outcomes manager is responsible for the development,
      implementation, and evaluation of an outcomes management program. One of the
      functions of an outcomes manager is developing collaborative practice teams to
      serve as vehicles of change through their analysis of outcomes data and the
      identification of best practice patterns. Interdisciplinary collaboration is a
      key component of an outcomes management program. Without an atmosphere os shared
      responsibility among disciplines for outcomes noted in a patient population, and
      recognition of individual expertise regarding care, efforts to produce change
      will move very slowly, if at all, and optimal improvements in care will be
      forfeited.

PMID- 9025504
TI  - Instability in Canadian Medicare: the case of dialysis delivery.

PMID- 9025505
TI  - Getting patients back to work: an update on the NKF Michigan Renal Rehabilitation
      Program.

PMID- 9025506
TI  - Provider helps working patients with a special evening shift. Interview by
      Melissa Coutts.

PMID- 9025507
TI  - Renal care in the "land down under".

PMID- 9025508
TI  - The World Council for Renal Care. A new approach to international nephrology.

PMID- 9025509
TI  - The Nurse Practice Act (NPA).

PMID- 9025510
TI  - Competency assessment.

PMID- 9025511
TI  - Accountability.

PMID- 9025512
TI  - Alarming trend in New York: 625 RNs to be replaced by unlicensed assistive
      personnel. What's in store for Nevada?

PMID- 9025513
TI  - Nurse ranks grow in legislative bodies nationwide.

PMID- 9025514
TI  - HIV/AIDS and Related Issues Forum.

PMID- 9025515
TI  - Nursing centers: the actualization of nurses.

PMID- 9025516
TI  - Nursing centers. An interview with a nurse working in a nursing center.

PMID- 9025517
TI  - The golden age of nursing education? Reflections on the Seventh International
      Nurse Education Tomorrow Conference--September 1996.

PMID- 9025518
TI  - Defining a model for team leader development.
AB  - This paper will provide details of a study conducted jointly by the authors
      following successful application to the Yorkshire Regional Health Authority in
      response to a call for proposals for studies into 'Practice-Led Education and
      Development'. The aim of the project was to pilot and evaluate an approach to
      leadership development based upon a conceptual model of reflectivity within a
      learning organization whilst developing and evaluating a model of supervised
      practice.

PMID- 9025519
TI  - Coping with the absurd: a first-time educational researcher's reflection.
AB  - Learning research through doing it often left me feeling confused, but I also
      experienced a well defined sense of 'well that's exactly what I thought all
      along', as I sought to clarify my uncertainties by turning to the literature.
      This feeling is, according to Schon & Bamberger, a type of historical revisionism
      where the student attributes insight to the moment when it occurs. They suggest
      that when the insight occurs, the 'moves on the way, tend to disappear' (1991,
      p207). This paper attempts to set down these moves and concludes with an
      exhortation to keep educational research rooted in the experience and interest of
      the student.

PMID- 9025520
TI  - Using simulation to test critical thinking skills of nursing students.
AB  - The purpose of this pilot study was to evaluate the effectiveness of using
      simulations to test critical thinking ability of nursing students. Nine medical
      and surgical videotaped vignettes were selected from the critical thinking
      component of the Performance Based Development System (PBDS). Pathology,
      difficulty rating and the obviousness of cues varied between vignettes. Each
      student was rated as acceptable, partially acceptable or unacceptable in their
      ability to identify a problem and provide appropriate nursing interventions with
      rationale for each vignette. A paper and pencil exercise and interviews were used
      to validate findings obtained from the video simulations. The pros and cons of
      using video simulations to assess critical thinking abilities of nursing students
      are discussed.

PMID- 9025521
TI  - Orientation to higher education: the challenges and rewards.
AB  - A new 'starter' course for qualified nurses entering higher education is
      discussed in this article. The background and aims of this course, which enables
      traditionally trained nurses to enter a pathway of professional and academic
      development, are presented. Learning outcomes of the course, identified through a
      formal evaluation procedure, were categorized into product and process
      components. Course teachers anticipated that the product outcomes would be
      evaluated most highly but the participants reported that the process outcomes
      were more important to them. They believed these process outcomes would empower
      them not only to undertake further academic studies but also to take a greater
      part in clinical decision-making. The results of this evaluation demonstrate that
      for many nurses, who seek to launch themselves into higher education, a
      'bridging' programme is necessary to support this transition.

PMID- 9025522
TI  - The utilization and evaluation of a simulation game in pre-registration nurse
      education.
AB  - The employment of simulations and games has been widely recommended for use in
      nurse education but there are few reports of their introduction or evaluation.
      This paper describes the use and evaluation of a simulation game which prepares
      students for a management module in an English National Board pilot scheme
      course. Evaluation took place by using a questionnaire completed by 528 students
      and by participant observation by the facilitators. The evaluation indicates that
      a simulation game is an appropriate way of preparing students for practice and
      that it provides a realistic and safe environment for enjoyable and meaningful
      learning to take place.

PMID- 9025523
TI  - An evaluation of the problem-solving ability of diplomates from a comprehensive
      nursing programme.
AB  - The aim of this South African study was to obtain a measurement of the problem
      solving ability of diplomates from a basic nursing programme with this skill
      included in its programme objectives. The problem-solving skills of diplomates
      from this programme were compared with those of first years to determine if there
      is an improvement in the problem-solving skills. A comparison was also made with
      a different basic programmes not claiming to teach problem-solving. The research
      design selected for this study was the ex post facto design. Data were collected
      using the Triple Jump Method which is an interview technique. The findings
      suggested that the level of the problem-solving skills of the comprehensive
      nursing programme diplomate is not satisfactory. There was, however, some
      improvement in the problem-solving ability from the first to the fourth year. The
      level of performance of the fourth years was slightly higher than that of the
      third years of the three-year nursing programme, who were used as the control
      group. Recommendations on selection teaching and evaluation of students, as well
      as further research, were made.

PMID- 9025524
TI  - An analysis of the concept facilitation.
AB  - This paper is an analysis of the concept facilitation. The analysis is based on a
      model suggested by Wilson (1969) cited in Walker & Avent (1988). The literature
      review shows the term used in physiological, educational,
      counselling/psychotherapy, social and theological contexts. The analysis leads to
      the compilation of the defining attributes of the concept facilitation which are:
      a process of enabling change; a climate for learning (mutual trust, acceptance
      and respect); and factors which relate to the nature of the process (student
      centred, negotiated and collaborative). The antecedents relate to the facilitator
      qualities (realness, caring and empathy), access to a learning situation and the
      effects of motivation and social influences; the consequences of effective
      facilitation being reciprocal change (learning and understanding), reciprocal
      feedback and increased independence. To a limited extent the empirical referents
      have been discussed. Cases have been constructed to provide examples of the term
      facilitation used in a model, borderline, related and contrary situations. The
      analysis will be of particular interest to those in nurse education.

PMID- 9025525
TI  - The benefits of Newman and Parse in helping nurse teachers determine methods to
      enhance student creativity.
AB  - Nurse educators have long been interested in producing graduates who are
      creative. But, what guidance is available which will assist faculty members in
      helping not hindering, the creativity of students? In this article, we address
      the guidance which is available in the nursing theories of Newman and Parse. In
      fact, we attempt to show that in operationalizing these theories, faculty members
      will also enhance their own creativity.

PMID- 9025526
TI  - Midwives' motivation for continuing education.
AB  - This study examined midwives' motivations for continuing their education by
      conducting a survey amongst a sample population of midwives, employed in 4 Health
      Authorities in the North West of England. The survey was carried out using a
      questionnaire which asked midwives to indicate the 'importance' of a series of
      requirements of continuing education. Of 120 midwives who received the
      questionnaire, 83 (69%) replied. Motivational factors included: learning for
      professional and personal development; fulfilling legal or statutory practice
      requirement, or as a social activity. The results showed that motivation for
      continuing education was strongest in relation to professional competence and an
      innate desire for knowledge. Where personal development was achieved, the
      emphasis was to promote professional advancement rather than social interaction.
      Less emphasis was placed on fulfilling the legal requirements for practice. The
      strongest motivators were learning orientated, which suggests that the subjects
      were self-directed to fulfil their needs, based on a desire to learn, this being
      less dependent on external motivators, which may be activated by statutory or
      employer requirements. Social interaction was seen as the least important aspect,
      although subjects found it beneficial to meet colleagues from other areas and
      felt that they learnt from exchanging views about various clinical practices.

PMID- 9025527
TI  - External review for promotion and tenure in schools of nursing.
AB  - To obtain information about external review for tenure and/or promotion, the
      faculty affairs committee in a large nursing program located in the southeastern
      United States conducted a survey among programs that award a doctoral degree in
      nursing. Research questions focused on general tenure and promotion policies,
      policies and procedures regarding the use of external review, and perceived
      advantages and disadvantages of external review. A 22-item survey was sent to 53
      institutions with a total of 34 usable surveys being returned. Findings revealed
      that a majority of the schools used external review, especially for tenure
      decisions and promotion to the associate and professor rank. Promotion and tenure
      criteria from individual schools were usually sent to reviewers along with the
      candidates' curriculum vitae and manuscripts. Candidates usually participated in
      the selection of external reviewers, but contact with reviewers was usually
      instituted by the administration within the institution. It was also felt that
      the advantage of external review far outweighed any disadvantages.

PMID- 9025528
TI  - Students in employment: learning and working.
AB  - The last two decades have witnessed the emergence of research findings in the
      field of education which clearly demonstrate the powerful influence of 'workload'
      on both what and how students learn. In nurse education, this notion of workload
      has focused on assessment demands and the dual role of the student nurse as
      learner and employee. Indeed it has only been with the implementation of the
      Project 2000 programmes of pre-registration nurse education that this latter
      aspect has been dealt a death blow. Or, has it? This paper presents a picture of
      current student nurses who should have greater educational freedom due to their
      supernumerary status. However, whilst not employees (as part of course
      participation), many students are participating in other employment. This
      phenomenon should be of interest to nurse educators because for many it presents
      the first opportunity for dealing with students in this situation.

PMID- 9025529
TI  - An exploratory study into the experience of part-time nurse teachers compared to
      full-time nurse teachers.
AB  - The part-time labour force, in nursing as elsewhere, is often unacknowledged, or
      conveniently assumed to have lesser commitment than the full-time labour force
      (Davies 1990). This paper reports the findings of an ethnographic study of five
      part-time nurse teachers and five full-time nurse teachers, which explored
      whether organisational and other constraints experienced by five part-time nurse
      teachers at one college of nursing, were the same for full-time nurse teachers.
      Four major themes emerged from the findings. Three constraints were identified by
      both part-time and full-time members, and they were related to issues of
      communication networks, valuing colleagues, and the results of coercive
      psychological contracts. The full-time teachers experienced these constraints but
      apparently to a lesser degree. The fourth theme was related to part-time teachers
      only. They identified that the flexibility of part-time hours enabled them to
      make compromises between their professional and other roles. The results of this
      study suggest that there is a need for part-time and full-time nurse teachers to
      work together in a collaborative manner, so that they are able to negotiate local
      working arrangements.

PMID- 9025530
TI  - NVQs in nursing, midwifery and health visiting: a question of assessment and
      training.

PMID- 9025531
TI  - Nursing in Academia.

PMID- 9025532
TI  - Nursing education: a junior doctor's view.

PMID- 9025533
TI  - The challenge of change in nurse education: traditionally trained nurses'
      perceptions of Project 2000.
AB  - Adapting to change can often be a difficult process. How traditionally trained
      nurses perceive the change brought about by Project 2000 is important, since this
      may affect how they view their own future, how they receive those who are
      qualifying via Project 2000 and how they work with Project 2000 diplomates in the
      future. It is, therefore, important that attempts are made to overcome any
      resistance to the changes brought about by Project 2000. The findings presented
      here are taken from the first questionnaire in a Department of Health-funded,
      longitudinal study into the careers of traditionally trained mental health
      nurses. Five hundred and fifty-six nurses were asked their views about the new
      training and how they thought it would affect them. Four hundred and forty-seven
      people returned the questionnaire: an 80% response rate. This study has revealed
      some positive views on Project 2000 as well as a variety of concerns.

PMID- 9025535
TI  - The changing roles of external examiners.
AB  - The nature and purpose of external examining and the role of external examiners
      are briefly discussed. Questions posed in Professor Silver's recent inquiry into
      undergraduate and postgraduate examinations is explained. Some answers and issues
      surrounding the questions raised in the inquiry are discussed at length. Notably,
      the perilous state of the current examiner system and the pitfalls facing
      educational centres are explored in detail.

PMID- 9025534
TI  - Student nurses' knowledge in relation to blood pressure measurement by
      sphygmomanometry and auscultation.
AB  - A 20-item questionnaire was used to explore student nurses' knowledge in several
      areas of blood pressure measurement by sphygmomanometry and auscultation.
      Questions were asked about factors that might influence blood pressure; on
      resting the subject before BP measurement; which arm should be used; the interval
      between repeat readings; the markings of the mercury column; on the details of
      sphygmomanometry technique and recording of the result. The questionnaire was
      administered to a group of Project 2000 students nearing the end of their common
      foundation programme. Out of 93 students, 78 consented to take part, representing
      84% of the cohort. Deficits were evident in students' background knowledge-90%
      had not heard of either Korotkoff sounds or auscultatory gap. Major deficits were
      also evident in the students' knowledge of correct measurement techniques. The
      results suggest that more attention is required in preparing students to carry
      out this basic nursing activity.

PMID- 9025536
TI  - Experiences of encouraging student-centred learning within a wellness-oriented
      curriculum.
AB  - This paper describes the use of learning logs as a tool for self-assessment and
      reflection during a 'well people' module within a Bachelor of Nursing programme.
      A qualitative analysis of the students' learning goals and reflective accounts
      from the learning logs are presented, together with extracts from the written
      evaluation of the module. Recommendations are made for enhancing the potential of
      the learning log as a flexible learning tool which can help students to draw upon
      professional knowledge in order to make sense of their experiences.

PMID- 9025537
TI  - The use of criteria-based grading profiles in formative and summative assessment.
AB  - This article outlines the development and use of criteria based grading profiles
      for formative and summative assessment. The profiles were developed in 1991 in an
      attempt to improve assessment validity, inter-marker and inter-course reliability
      and student feedback within the Faculty of Health Care and Social Studies.
      Important underlying aspects of assessment theory are examined and it is argued
      that assessment should be conceptualised as an ethical activity requiring
      clarification for students of expectations through specification of criteria. It
      is concluded that the profiles have proved useful in guiding both lecturers and
      students in the completion and marking of assessed work and that further study
      and debate needs to take place in relation to the effectiveness and potential
      disadvantages of such profiles.

PMID- 9025538
TI  - Promoting reflection in postgraduate nursing: a theoretical model.
AB  - Reflection is a method of learning and teaching professional maturity through
      critical analysis of experience. Illuminative research approach is used in
      collaboration with students on a palliative care course to investigate the
      effects of reflective learning 1 year after the course. Questionnaire and
      interview methods were used to collect data. This study concludes that (1)
      critical thinking is notably augmented, (2) listening and observation skills are
      enhanced and (3) gaining insight into clinical situations and personal nursing
      philosophy and approaches are essential for discovery of theories of nursing.

PMID- 9025539
TI  - Nurse education consultancy: a new role.
AB  - Market philosophy is transforming nurse education, an arena where alternative
      values and beliefs have been important. Such philosophy challenges nurse teachers
      to rethink their roles and consider what they might have to offer the profession
      either working within an institution or independently. This paper will explore
      the role of the nurse education consultant, examining what is implied by the term
      'consultation' and what this might mean within a consultation process.
      Consultancy may be used to help colleges to market effectively and ethically,
      when the benefits of long term investment in education may not otherwise be
      apparent.

PMID- 9025540
TI  - Factors influencing the branch choice of students on a nursing undergraduate
      programme.
AB  - This study considered the factors that influenced the branch choice of students
      on a nursing undergraduate programme. On entry to the course students had to
      choose to pursue a programme either in adult general nursing or mental health
      nursing to honours degree level. A review of the literature on Project 2000 and
      factors influencing students' choice of nursing, and of particular specialisms
      identified, indicated factors which may have relevance to branch choice.
      Quantitative data were obtained through questionnaire (n = 28). Second
      qualitative data were collected by semistructured interview (n = 12). The
      findings of the study suggest that factors influencing branch choice are
      multiple, complex, inter-related and individual. Whilst the size of the sample
      groups were small some tentative implications for nurse education are examined.

PMID- 9025541
TI  - Student reflective groups at a Scottish College of Nursing.
AB  - In this paper student views on reflective groups, set up as an important element
      of the new Project 2000 course in a Scottish College of Nursing, are reported. A
      random sample of 19 students were interviewed. While the reflective groups were
      very popular with students because they provided support, there was little
      evidence of a linkage between theory and practice. It was clear that the
      ambitious objective of stimulating reflection-on-action was not attained.
      Practice certainly was discussed, but it tended to be dominated by dramatic and
      emotionally charged aspects of care rather than the more frequent routine
      concerns. There were, however, indications that the original aim of the
      reflective groups could be achieved if tutors could establish a common
      understanding of the purpose of the groups and of reflection, and if the
      practices on which students reflected consisted less of single day visits where
      the students saw themselves as nonparticipant outsiders.

PMID- 9025542
TI  - Nursing education: the marriage of two normative worlds--creating a sustainable
      relationship?

PMID- 9025543
TI  - Where's the real crisis in health care?

PMID- 9025544
TI  - The B.C. Baby-Friendly Initiative.

PMID- 9025545
TI  - First call.

PMID- 9025546
TI  - Nurses rate RNABC "quite effective".

PMID- 9025547
TI  - Supporting colleagues with practice concerns.

PMID- 9025548
TI  - Nursing in the urban core. Interview by Helen Griffiths.

PMID- 9025550
TI  - Integrating evidence-based clinical tools with practice.

PMID- 9025549
TI  - Connecting with colleagues. Interview by Helen Griffiths.
AB  - How does a nurse go about maintaining her level of competence when she is one of
      the few local practitioners in her field? Vancouver sex therapist Bianca Rucker
      is doing it by cultivating a network of colleagues and mentors in related fields
      both at home and across the continent.

PMID- 9025551
TI  - Nursing advocacy extends to clients, workplaces and society.

PMID- 9025552
TI  - Midwifery soon to be an option in B.C. for low-risk births.
AB  - Midwifery has recently been established in British Columbia as a self-regulating
      profession with its own regulatory body, the College of Midwives of British
      Columbia. Within the next few months, registered midwives will join the other
      members of the health care team as legitimate providers of care for childbearing
      women and their families. Midwifery care will be an option for low-risk women
      who, as long as they continue to experience a healthy pregnancy, will be able to
      choose to give birth attended by a midwife.

PMID- 9025553
TI  - Integrating traditional beliefs with western practice.
AB  - In the Vietnamese culture, health is considered to be a delicate balance of a
      number of forces. But what happens when pregnancy and childbirth disrupt this
      balance? Donna Shareski looks at how nurses in Canada can provide quality care to
      expectant Vietnamese mothers while still allowing them to preserve their
      traditional ways.

PMID- 9025554
TI  - What you see is what you get (or is it?).

PMID- 9025555
TI  - Female foeticide. A danger to society.

PMID- 9025556
TI  - Nurses at stress.

PMID- 9025557
TI  - Fighting leprosy.

PMID- 9025558
TI  - Leave entitlements under the ADA and the FMLA.

PMID- 9025559
TI  - ANA and Kent State University launch new online journal.

PMID- 9025560
TI  - What is my responsibility when working with a physician assistant?

PMID- 9025561
TI  - Turning lemons into lemonade: downsizing can create new opportunities and
      challenges.

PMID- 9025563
TI  - On the road to Oz.

PMID- 9025562
TI  - New strategic plan developed to prepare ONS for the 21st century.

PMID- 9025564
TI  - Nursing quality indicators needed in Pennsylvania.

PMID- 9025565
TI  - ANA Leadership Development Seminar sparks critical thinking.

PMID- 9025566
TI  - Career clinic. How to improve your communication skills.

PMID- 9025567
TI  - Powerlessness in chronic illness.

PMID- 9025568
TI  - Breast cancer detection practices in North Dakota's rural long-term care
      facilities.

PMID- 9025569
TI  - Nurse in profile: RFDS registered nurse.

PMID- 9025572
TI  - Community health nurses--their role and their future.

PMID- 9025570
TI  - Sexual harassment? It couldn't happen to me!

PMID- 9025571
TI  - Shiftwork--guidelines for roster design.

PMID- 9025573
TI  - Liability for allowing hostile work environment.

PMID- 9025574
TI  - Nurse recovers for violation of Pregnancy Discrimination Act. Case in point:
      Garcia v. Woman's Hosp. of Texas 97 F. 3d 810--TX (1996).

PMID- 9025575
TI  - Legal case briefs for nurses. WV: urine screen "positive for cocaine": five year
      license suspension upheld; CA: injury in treatment for "needle stick": "Dual
      Capacity" Doctrine not applicable.

PMID- 9025576
TI  - Nurse seeks post-traumatic stress disorder compensation. Case in point: Renter v.
      Willis-Knighton Med. Center 679 So. 2d 603--LA (1996).

PMID- 9025577
TI  - [Do you know the AIDS virus?].

PMID- 9025578
TI  - [Asthma, of greater importance than ever].

PMID- 9025579
TI  - [The science of asthma, a promising discipline for the last 2000 years].

PMID- 9025580
TI  - [Understanding in order to take better care of oneself and to live better].

PMID- 9025581
TI  - [Asthma, towards a model of education in public health].

PMID- 9025582
TI  - [Children's asthma ... it is real asthma].

PMID- 9025583
TI  - [Sports in the grass ...or ... out of breath?].

PMID- 9025584
TI  - [In school at the climate college of Auvergne Sancy].

PMID- 9025585
TI  - [Control of asthma by children: myth or reality?].

PMID- 9025586
TI  - [Carrying out a service project: from inception to action].

PMID- 9025588
TI  - [Our health ... that is our business].

PMID- 9025587
TI  - [The selective sorting of hospital refuse].

PMID- 9025589
TI  - [Health records have arrived...].

PMID- 9025591
TI  - Perioperative nursing education "down under".
AB  - Perioperative nurses in Australia are concerned with a number of significant
      challenges. First, they are concerned with the international trend of increased
      use of nonursing personnel within operating theaters. They believe that this may
      have detrimental effects on patient care. Second, is the issue of maintaining an
      adequate supply of professionally prepared perioperative nurses. Within this
      article, initiatives to address these challenges are discussed.

PMID- 9025592
TI  - Clinics in perioperative nursing: Brunei Darussalam.
AB  - This article gives a brief account of the developments in nursing in general and
      in perioperative nursing in particular in Brunei Darussalam. From a small
      hospital school, nurse education has taken bold strides and is now firmly
      established in the tertiary setting. General and specialist courses are taught,
      and recently a course in operating department nursing has been developed. Every
      effort is made to offer the perioperative patient the highest standards of care
      through education for caring at the College of Nursing Brunei Darussalam.

PMID- 9025593
TI  - Surgical preadmission clinics in Canada: the expanding need with changing
      technologies.
AB  - The authors describe the staff development and expansion of a preadmission clinic
      in one Canadian teaching hospital. The nurses' shift in focus from technical
      skills to assessment, education, and counseling skills is described. The benefits
      observed from an increasing preadmission service are also high lighted.

PMID- 9025594
TI  - Perioperative nursing in Greece.
AB  - In Greece perioperative nursing is comprised of preoperative, intraoperative, and
      postoperative nursing. Nursing care in these phases involves general and
      presurgical preparation, all activities performed during surgery, and the care
      given in both the recovery room and clinical unit after surgery.

PMID- 9025595
TI  - Factors affecting the development of postoperative complications in Iraq.
AB  - Factors associated with the development of postoperative complications are well
      documented in the literature. However, local, national, and international factors
      external to hospital-based health care can influence the adequacy of both human
      and medical resources and thus, potentially, the incidence of postoperative
      complications.

PMID- 9025596
TI  - Parental participation during induction stage of children's anesthetic procedures
      in Israel.
AB  - Recognition of the long-term emotional effects on children being hospitalized for
      surgery and changes in the perception of children's rights have led to changes in
      nursing care on pediatric surgical wards and in staff attitudes. The tendency has
      been to involve the parents as much as possible in the pre-surgical procedure,
      thus decreasing anxiety and fear both in parents and children. The nursing staff
      at Schneider Children's Medical Center of Israel has implemented a new policy and
      procedure for admitting children to the operating room. Parents are permitted to
      accompany the child to the operating room and to stay until the child falls
      asleep. The parents' presence contributes to the child's mental and emotional
      health and increases the child's self-confidence. Our experience indicates that
      parental participation facilitates the anesthetic procedure and makes it less
      traumatic. We conclude that parents, participation during surgical induction
      plays an important role in helping the child cope with this traumatic experience.

PMID- 9025597
TI  - Perioperative nursing--the Jamaican perspective.
AB  - Under constraints of a restricted economy Jamaica strives to deliver health care
      at the standard of developed countries. Nurses in Jamaica assume various roles as
      they provide perioperative nursing care; they work as a team and act as patient
      advocates. Bonds of caring and love are often established between patients,
      families, and the nursing staff. The quality of nursing care often determines the
      client's perioperative outcome, and Jamaican nurses strive to meet the challenges
      inherent in achieving positive patient outcomes.

PMID- 9025599
TI  - An overview of perioperative nursing in Kenya: issues, challenges, and trends.
AB  - No conscientious nurse involved in perioperative nursing in Kenya can afford to
      be isolated from the special needs and circumstances that apply to all nurses in
      this country. These needs and circumstances are very real and very compelling in
      determining the pattern of perioperative nursing and enforcing a logical solution
      to the problems of broken equipment, shortage of supplies, and understaffing.

PMID- 9025598
TI  - The effect of unit type and gender on Jordanian nurses' job satisfaction: a
      comparison of operating room, medical-surgical, and critical care nurses.
AB  - This study examines the quality of nursing work life for men and women in Jordan.
      Specifically it focuses on similarities and differences across three unit types:
      operating room, intensive care/critical care, and medical-surgical. Findings
      suggest that both gender and unit type should be considered when examining
      nurses' perceptions of the quality of work life.

PMID- 9025600
TI  - Case study: perioperative nursing in Nepal.
AB  - The author presents a demographic and economic profile of Nepal, briefly
      describes its health care system, traces the development of nursing in Nepal, and
      uses a case study to describe perioperative nursing care in Nepal. The patient,
      who was diagnosed as having adenocarcinoma of the stomach, received care at the
      only teaching hospital in Nepal, and the author describes the patient's care from
      prediagnosis through discharge.

PMID- 9025601
TI  - Oplan Sagip Mata: Philippine style.
AB  - Oplan Sagip Mata is a multisectoral effort for visual health. The movement was
      launched with the overall aim of advocating primary eye care and addressing the
      grievous concern for the enormous backlog of cataract cases. This article
      describes Oplan Sagip Mata as the social marketing component of the Prevention of
      Blindness Program of the Department of Health in the Philippines.

PMID- 9025602
TI  - Perioperative care and the role of the theater nurse: a Swedish perspective.
AB  - A model for perioperative care has been used in which the theater nurse visits
      the patient both before and after surgery. The model stresses a holistic patient
      view. Preoperative and postoperative visits enable the nurse to give and discuss
      detailed information about all aspects of the surgery. Experiences from using the
      model during the last 6 years are reported and discussed.

PMID- 9025603
TI  - Perioperative nursing care at Muhimbili Medical Center: a proposal for
      improvement.
AB  - Observations have suggested that, although routine nursing procedures such as
      checking vital signs and making beds were being performed, interventions
      addressing specific aspects of perioperative nursing were being overlooked in
      Tanzania. Thus, a study is being designed to determine how well patients are
      being cared for throughout the perioperative experience at Muhimbili Medical
      Centre (MMC), Dar es Salaam, Tanzania.

PMID- 9025604
TI  - Overcoming the challenges of nursing in Turkey.
AB  - The effectiveness of nursing interventions must be evaluated and nursing practice
      supported by research findings. Nurses in many countries, however, are confronted
      not only by the challenge of conducting research, but also by the challenge of
      providing nursing care. This article reviews the importance of planned
      preoperative respiratory exercises and describes how Turkish nurses were able to
      conduct a study designed to explore the effectiveness of this nursing
      intervention by capitalizing on a study being done by physicians. Although
      nursing research has the potential to improve patient care, such an outcome
      depends on implementing findings, which in a clinical setting hinges on adequate
      staffing.

PMID- 9025605
TI  - Quality and patients' expectations of a surgical admission: a Welsh perspective.
AB  - The authors report a study undertaken to identify the expectations of patients
      before a surgical admission. Respondents experienced difficulty in articulating
      their expectations of surgery. Interviewees believed that the level of
      information available before admission was unsatisfactory.

PMID- 9025606
TI  - Preoperative nursing in Zimbabwe.
AB  - Perioperative nursing is a term used to describe the variety of nursing functions
      associated with the patient's surgical experience. However, with the exception of
      a few variations to accommodate local conditions and cultural considerations
      nursing interventions of the preoperative, intraoperative, and postoperative
      phases are no different from those in other parts of the world. This article
      describes preoperative nursing in Zimbabwe.

PMID- 9025607
TI  - [Kidney-pancreas transplantation].

PMID- 9025608
TI  - [Kidney-pancreas transplantation. Organ procurement in France. Organization and
      legislation].

PMID- 9025609
TI  - [Kidney-pancreas transplantation. Coordination in the hospital].

PMID- 9025610
TI  - [Kidney-pancreas transplantation. Indications for double transplantations].

PMID- 9025611
TI  - [Combined kidney and pancreas transplantation. Surgical technique].

PMID- 9025612
TI  - [Kidney-pancreas transplantation. The role of the operating room nurse].

PMID- 9025613
TI  - [Kidney-pancreas transplantation. Preoperative and postoperative care].

PMID- 9025614
TI  - [Kidney-pancreas transplantation. Patient education and follow-up].

PMID- 9025615
TI  - [Kidney-pancreas transplantation. Drug therapies].

PMID- 9025616
TI  - [Kidney-pancreas transplantation. The results].

PMID- 9025617
TI  - [Creutzfeldt-Jacob disease. Precautions to be taken for patients with suspected
      or real infections].

PMID- 9025619
TI  - [Peridural and arachnoid anesthesia].

PMID- 9025620
TI  - [Pediatric stoma therapy].

PMID- 9025618
TI  - [Surgery during full hospitalization].

PMID- 9025621
TI  - [Pediatric stoma therapy. Structure of care. Assignments of the managing nursing
      staff].

PMID- 9025622
TI  - [Pediatric stoma therapy. Techniques and materials].

PMID- 9025623
TI  - [Pediatric stoma therapy. Feeding children with stomas].

PMID- 9025624
TI  - [Pediatric stoma therapy. Psychological care].

PMID- 9025626
TI  - [Corneal injury without an intraocular foreign body].

PMID- 9025625
TI  - [Pediatric stoma therapy. The social worker's viewpoint].

PMID- 9025627
TI  - [Hygienic care of children].

PMID- 9025628
TI  - [Psychomotor instability].

PMID- 9025629
TI  - [The father in the life of mother and child].

PMID- 9025630
TI  - Tennessee Nurses Association. Resolution. In support of HIV/AIDS preventive
      vaccine research.

PMID- 9025631
TI  - Babies at risk. Can the prenatal care initiative be saved?
AB  - My husband and I named our lovely daughter Faith because of the enormous
      obstacles we faced in getting her here safe and sound...I almost gave up hope
      that I would receive any help at all...I called Physicians Referral at least a
      dozen times, saying, please give me leads to possible people who accept Medicaid.
      The answer was a flat "nope."...I went to the bookstore and bought a couple of
      books on how to take care of myself during pregnancy...I am angry that not only
      every physician I asked refused to see a Medicaid patient, that they would also
      not refer me to the one facility within a 100 mile radius that did...I began
      going there (with nurse-midwives at Monroe Maternity Center) in January and I can
      tell you I received the best treatment, the only drawback was driving an hour and
      a half one way to receive each prenatal check up... Faith may be the most
      important person in the world to me. She may be the apple of her daddy's eye, but
      Tennessee and the majority of the medical community could care less about whether
      she lives or dies...

PMID- 9025632
TI  - Diabetes coalition recommends new minimum guidelines.

PMID- 9025633
TI  - Nursing educators lead change.

PMID- 9025634
TI  - Managed care and nurses' roles.

PMID- 9025635
TI  - 'A glimpse over the horizon'.

PMID- 9025636
TI  - Minimally invasive instrument streamlines breast biopsy procedure.
AB  - A new technology makes breast biopsy less traumatic for the patient. Breast
      biopsy now may be performed in a doctor's office under local anesthesia. Pain and
      disfigurement from a breast biopsy is avoided by a minimally invasive procedure.

PMID- 9025637
TI  - The efficacy of the ASTM's barrier tests even a 'pass' can fail in use!
AB  - The barrier protection quality of materials is an important issue in the OR. Some
      tests of barrier effectiveness can be inappropriate in relation to actual use.
      Upcoming test methods may change the basis on which a material's barrier quality
      is evaluated.

PMID- 9025638
TI  - Phacoemulsification needle enhances cataract surgery.
AB  - Phacoemulsification, a cataract removal technique, can be facilitated by certain
      instruments. A micro-incision needle can help improve surgical team comfort and
      patient outcomes. Infusional flow helps prevent thermal damage and wound leakage
      in the eye.

PMID- 9025639
TI  - Surgical technologists advance practice and profession at Indiana Hospital.
AB  - The surgical technologist can be a cost-effective staff member in the OR. Techs
      work with RNs as part of the important team of perioperative and intraoperative
      patient care providers. All who work in the OR, including techs, are responsible
      for its cost effectiveness.

PMID- 9025640
TI  - Repairing acquired ptosis.

PMID- 9025641
TI  - Expanding the role of the surgical nurse to veterinary medicine.

PMID- 9025642
TI  - Your rights as an employee (Part 1).

PMID- 9025644
TI  - Medicaid ... one runaway train seems to be slowing down.

PMID- 9025643
TI  - Sheep-dip chaplaincy.

PMID- 9025645
TI  - Employers ... General Motors.

PMID- 9025647
TI  - Liability ... new law in Pennsylvania.

PMID- 9025646
TI  - Business. The next big thing.

PMID- 9025648
TI  - Information systems ... health care lags behind other fields.

PMID- 9025649
TI  - Integration. Hospitals still hanging their hopes on PHOs.

PMID- 9025650
TI  - Managed care. Where it's at.

PMID- 9025651
TI  - The CEO as politico. Interview by Harris Meyer.

PMID- 9025652
TI  - A piece of the action.

PMID- 9025653
TI  - Let the games begin ... again.
AB  - Brace yourself for a new round of Medicare politics. Behind bipartisan smiles
      lurk deep divisions. Whatever the makings--or breakings--of a deal between
      President Clinton and the Republican Congress, you can count on this: a clash of
      political titans.

PMID- 9025654
TI  - Physician, deal thyself.
AB  - Times are booming for practice management companies. With many doctors eager to
      sell their practices, Wall Street is bullish on the firms lining up to buy them.
      But after some disappointments, the luster may be wearing off. Find out why in
      this Executive Chartbook exclusive.

PMID- 9025655
TI  - Stargazing: 1997 NOVA Award winners.

PMID- 9025656
TI  - Consumers. Getting the lowdown on doctors.

PMID- 9025657
TI  - Downsizing. Cutting with kindness.

PMID- 9025658
TI  - Finance. Back talk over contracts.

PMID- 9025659
TI  - Medicaid. Arizona voters up the ante.

PMID- 9025660
TI  - Employee benefits. The doctor is in.

PMID- 9025661
TI  - Managed care. Will U.S. HMOs play in Pretoria?

PMID- 9025662
TI  - Charged to mentor.

PMID- 9025663
TI  - Neuromuscular blocking agents.

PMID- 9025664
TI  - Pain ratings: the fifth vital sign.

PMID- 9025665
TI  - Using breathing to supplement pain control.

PMID- 9025668
TI  - Smoothing the CABG patient's road to recovery.

PMID- 9025669
TI  - Clinical snapshot: thrombotic thrombocytopenic purpura.

PMID- 9025670
TI  - Emergency! Spontaneous pneumothorax.

PMID- 9025671
TI  - The abusive patient: where do you draw the line?

PMID- 9025672
TI  - How to guide ventilator-dependent patients from hospital to home.

PMID- 9025673
TI  - Maintaining skin integrity during radiation therapy.

PMID- 9025675
TI  - 'Don't become involved'.

PMID- 9025676
TI  - Quality and staffing issues dominate the ANA agenda.

PMID- 9025677
TI  - Infection risk from contaminated endoscopes.

PMID- 9025678
TI  - Growth and change through nurse internships.

PMID- 9025679
TI  - Demonstrating nursing's value in community health.

PMID- 9025680
TI  - Aminoquinolines that circumvent resistance in Plasmodium falciparum in vitro.
AB  - Aminoquinoline (AQ) resistance is one of the most important factors in the
      worldwide resurgence of malaria due to Plasmodium falciparum. We synthesized a
      series of AQs to define the structure-activity relationships responsible for AQ
      action against chloroquine-susceptible and -resistant P. falciparum. The AQs with
      ethyl, propyl, isopropyl, butyl, pentyl, isopentyl (chloroquine), hexyl, octyl,
      decyl, or dodecyl side chains were equally active against chloroquine-susceptible
      P. falciparum (50% inhibitory concentrations [IC50s] = 5-15 nM). The AQs with
      ethyl, propyl, isopropyl, decyl, or dodecyl side chains were also active against
      chloroquine-, mefloquine- and multiply-resistant P. falciparum (IC50s = 5-20 nM).
      Verapamil, which enhances the activity of chloroquine against chloroquine
      resistant parasites, had no effect on the activity of AQs that were active
      against resistant parasites. These results indicate that AQs with 2-12 carbon
      side chains are as active as chloroquine against chloroquine-susceptible P.
      falciparum, and that AQs with side chains shorter or longer than chloroquine are
      often active against chloroquine-, mefloquine-, and multiply-resistant P.
      falciparum.

PMID- 9025681
TI  - Short report: case report of Cyclospora infection acquired in Indonesia and
      treated with cotrimoxazole.
AB  - A detailed chronology of unsuccessful efforts to diagnose and treat a sudden
      onset case of chronic diarrhea acquired in Jakarta Indonesia, and ultimately
      attributed to Cyclospora is presented. A modified Kato technique was used to
      quantify Cyclospora oocysts during successive days prior to, during, and after
      successful cotrimoxazole therapy (160 mg of trimethoprim, 800 mg sulfamethoxazole
      twice a day for seven days) for this infection. Cyclospora was associated with
      6.4% of the gastrointestinal illness and/or diarrhea cases that presented during
      a seven-month period to a Jakarta clinic that serves a small population of
      expatriates. Cyclospora and Giardia lamblia were identified with equal frequency
      during this period and were the dominant pathogenic intestinal parasite species
      found in this community.

PMID- 9025682
TI  - The efficacy of pentamidine in the treatment of early-late stage Trypanosoma
      brucei gambiense trypanosomiasis.
AB  - Fifty-eight patients in the early-late stage (early central nervous system
      involvement) of Trypanosoma brucei gambiense trypanosomiasis were treated with
      pentamidine and divided into four groups (G1, G2, G3, and G4) according to
      cerebrospinal fluid (CSF) indicators: white blood cell (WBC) count, protein level
      (CSF protein), and the presence or absence of trypanosomes. Group G1 consisted of
      eight patients with normal CSF WBC counts and CSF protein levels and trypanosomes
      in the CSF. Group G2 consisted of nine patients with elevated CSF WBC counts,
      normal level of CSF protein, and trypanosomes in the CSF. Group G3 consisted of
      31 patients with high CSF WBC counts, normal CSF protein levels, but no
      trypanosomes in the CSF. Group G4 consisted of 10 patients with normal CSF WBC
      counts and CSF protein levels and trypanosomes demonstrated by CSF culture. Post
      treatment follow-up of all patients for at least one year revealed three
      relapses. There were two deaths from diseases unrelated to trypanosomiasis or to
      the treatment protocol. Of these patients, 52 were followed for more than two
      years, the time necessary to confirm a complete cure, indicating a cure rate of
      94%. Pentamidine is therefore effective in treating the early-late stage of T. b.
      gambiense trypanosomiasis, and is comparable with melarsoprol or eflornithine in
      terms of its tolerance and availability.

PMID- 9025683
TI  - Microsatellite polymorphism in Anopheles maculatus, a malaria vector in Thailand.
AB  - Dinucleotide microsatellites were characterized from Anopheles maculatus, a
      species of mosquito that transmits malaria. A partial genomic library of An.
      maculatus, consisting of 3,960 kilobases (kb), was screened with either (GT)12 or
      (CT)12 probes. Approximately 1.5% of the recombinants contained sequences that
      hybridized to either (GT)12 or (CT)12 dinucleotide probes, suggesting that
      microsatellites are abundant in the genome of An. maculatus. Estimation of
      abundance of the two dinucleotide repeats revealed that (GT)n or (CA)n
      microsatellites occur on average every 68 kb and (CT)n or (GA)n repeats every 495
      kb. Among 23 microsatellite loci sequenced, four loci were selected to synthesize
      primers to perform polymerase chain reaction scoring for genetic polymorphism in
      a population of An. maculatus. A high level of polymorphism was observed with all
      four microsatellite loci analyzed. The number of alleles detected at each locus
      ranged from eight to 12 and the heterozygosities ranged from 0.25 to 0.54. A
      total of 42 alleles were found among four microsatellite loci. The large number
      of alleles and polymorphic nature resolved from microsatellite loci make these
      markers valuable for the study of population genetic structure and gene flow.
      Knowledge of gene flow is required to develop vector control strategies using
      genetic manipulations of malaria vector populations.

PMID- 9025684
TI  - Rapid postmortem invasion of cecal mucosa of macaques by nonpathogenic Entamoeba
      chattoni.
AB  - Although Entamoeba histolytica is the third leading parasitic cause of death in
      the world, most infections in humans are asymptomatic and restricted to the
      intestinal lumen. Entamoeba histolytica infections have also been reported in
      most species of captive nonhuman primates, with New World monkeys being
      particularly susceptible to fatal invasive amebiasis. In contrast, Old World
      monkeys appear to be resistant to the disease, although tissue invasion in
      asymptomatic monkeys has been reported. Our initial objectives were to determine
      the incidence, the predisposing factors, and the light microscopic and
      ultrastructural features of invasive amebiasis in Macaca mulatta (rhesus) and and
      M. fasicularis (cynomolgus) macaques. Our findings indicate that nonpathogenic E.
      chattoni in macaques can invade cecal mucosa rapidly (within 1 hr) after death.
      Therefore, the presence of invasive Entamoeba trophozoites in routinely collected
      necropsy materials should be interpreted with caution, particularly in cases
      where tissue fixation is delayed.

PMID- 9025685
TI  - Complete nucleotide sequence of the genome of Japanese encephalitis virus ling
      strain: the presence of a 25-nucleotide deletion in the 3'-nontranslated region.
AB  - The complete sequence of the genome of the Japanese encephalitis virus (JEV) Ling
      strain isolated from the brain of a patient in Taiwan in 1965 was cloned by using
      the reverse transcription-polymerase chain reaction method. Seven overlapping
      cDNA clones that span the entire virus genome were isolated and sequenced to
      determine the complete nucleotide sequence, which is 10,951 nucleotides in
      length. As reported for three other JEV strains (Beijing-1, SA-14, and
      JaOArS982), the Ling strain contains 95 nucleotides in the 5' nontranslated
      region (NTR), followed by a single open reading frame of 10,296 nucleotides.
      However, the length of the 3' NTR of JEV Ling is 560 nucleotides, 25 nucleotides
      shorter than that of other JEV strains sequenced to date. Comparison of
      nucleotide and amino acid sequences among these four JEV strains showed that
      nucleotide (amino acid) sequence divergence in the translated region varied from
      1.25% to 3.27% (0.49-1.63%). The nucleotide (amino acid) divergences between the
      Ling and Beijing-1 strains were 1.25% (0.87%) and between the SA-14 and JaOArS982
      strains were 1.42% (0.49%). These values are lower than those found between the
      Ling and SA-14 [2.44% (1.02%)] or the Ling and JaOArS982 strains [2.84% (0.93%)],
      as well as those between Beijing-1 and SA-14 [3.14% (1.60%)] or Beijing-1 and
      JaOArS982 [3.27% (1.63%)] strains. Sequence comparisons of subregions of the
      genomes i.e., structural genes, nonstructural genes, or individual genes, showed
      divergence similar to that obtained by comparing the entire sequence. It is
      likely that the JEV sequence divergence between two human isolates or between two
      mosquito isolates is lower than that between a human isolate and a mosquito
      isolate.

PMID- 9025686
TI  - Growth promotion of Mycobacterium avium-M. intracellulare complex by
      enterobacterial acetate.
AB  - A mycobacterial growth factor was present in the conditioned media of Escherichia
      coli and Enterobacter cloacae cultures, but not in Pseudomonas aeruginosa
      culture. This factor potentiated the growth of Mycobacterium avium-M.
      intracellulare complex (MAC), a patient isolate, and well-established strains of
      M. avium and M. intracellulare. The growth factor was not a polypeptide; it was
      heat-stable and possessed a molecular weight < 500 D. Acetate production by
      enterobacteria was responsible for the biological activities observed. Acetate
      promoted mycobacterial growth at concentrations up to 3 mM; higher levels were
      toxic. The effects of acetate on MAC growth were not influenced by the pH of the
      media. Our data suggest that production of acetate by enterobacteria may regulate
      mycobacterial growth, and therefore, intestinal acetate might be a cofactor in
      the pathogenicity of MAC.

PMID- 9025687
TI  - Strongyloides stercoralis: maintenance of exceedingly chronic infections.
AB  - Two hypotheses were tested to identify the mechanism(s) by which chronic
      Strongyloides stercoralis infections are maintained in experimental dogs as a
      model to explain delayed onset recrudescence in humans. Investigations tested the
      hypotheses that chronic infections result from 1) periodic reactivation of third
      stage larvae from a reservoir of dormant parasites outside the gastrointestinal
      tract or 2) the periodic rejuvenation of postreproductive female worms remaining
      from a previous infection, lodged in the mucosal crypts. Populations of
      parenteral larvae survived in mature experimentally infected female dogs for 66
      days; individual worms survived for 88 days, but there was no evidence that these
      larvae re-established patent, adult worm infections. Late in these infections,
      female worms were present in greater than predicted numbers with no evidence that
      autoinfection had occurred, suggesting that some postreproductive worms were long
      lived. In separate trials, long-lived spent females were once again capable of
      producing viable larvae when the host was treated with corticosteroids.

PMID- 9025688
TI  - Characterization of Trypanosoma cruzi populations by zymodemes: correlation with
      clinical picture.
AB  - Trypanosoma cruzi isolated from 55 chronic chagasic patients were grouped into
      isozymic strains on the basis of electrophoretic patterns for a set of six
      enzymes. The total sample showed a distribution of asymptomatic (63.6%) and
      clinically ill (36.4%) patients similar to that generally reported for Chagas'
      disease. Six of the 12 zymodemes known to exist in Argentina have been isolated
      from humans. Only two (Z1 and Z12) are frequent and widely distributed in the
      endemic area. These two zymodemes differ significantly in their pathogenicity.
      The proportion of asymptomatic patients was higher with the Z1 zymodeme (81.1%)
      than with the Z12 zymodeme (27.3%). The incidence of heart alterations was lower
      in Z1 than in Z12 zymodeme patients (18.9% versus 72.7%). Clinically evident
      acute disease was seen in 36.3% of cases with zymodeme Z12 and in 8.1% of cases
      with zymodeme Z1. The differences between the two prevalent zymodemes in
      Argentina are statistically significant. These observations indicate that the Z1
      T. cruzi is a more benign strain than Z12. Patients infected with Z1 would be
      more likely to be asymptomatic for a longer time than those infected with Z12.
      The risk of cardiac lesion would be greater for patients harboring Z12 T. cruzi
      than for those with Z1. The results suggest that strain identification could be a
      useful prognostic tool.

PMID- 9025689
TI  - Soluble cell adhesion molecules in human Chagas' disease: association with
      disease severity and stage of infection.
AB  - Formation of inflammatory lesions, one of the pathologic consequences of
      infection with Trypanosoma cruzi, involves intricate cell-cell interactions in
      which cell adhesion molecules (CAMs) are involved. Sera from 56 Chagas' disease
      patients grouped according to disease severity were studied for the presence of
      soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble endothelial
      selectin (s-E-selectin), soluble vascular cell adhesion molecule-1 (s-VCAM-1),
      soluble platelet selectin (s-P-selectin), and s-CD44 were studied to determine if
      they could be used alone or in different combinations as markers for specific
      diagnostic procedures. Comparisons were made between congenitally, acutely, and
      chronically infected patients and aged-matched, noninfected individuals, as well
      as between patients with chronic Chagas' disease grouped according to the
      severity of their heart-related pathology. No differences in levels of s-CAMs
      were detected between sera from children with congenital T. cruzi infection and
      sera from noninfected infants born from chagasic mothers. In contrast, titers of
      s-ICAM-1, s-VCAM-1, s-selectin, and s-CD44 but not s-P-selectin were
      significantly increased in sera from patients during the acute phase of infection
      with T. cruzi. Titers of s-VCAM-1 and s-P-selectin were increased in chronically
      infected patients. A positive association with disease severity in sera from
      patients with chronic disease was observed for the levels of s-P-selectin. In
      contrast, we found no association between clinical symptoms and levels of s-VCAM
      1. Patients with chronic disease with severe cardiopathy also showed diminished
      levels of s-CD44 in comparison with healthy controls or patients with mild
      disease. The results are discussed in the context of pathology of Chagas'
      disease.

PMID- 9025690
TI  - Immunogenicity of the nonrepetitive regions of the circumsporozoite protein of
      Plasmodium knowlesi.
AB  - The circumsporozoite antigen (CS) of the simian malarial parasite Plasmodium
      knowlesi consists of tandemly repeated immunodominant peptide units that are
      variable and may play a role in evading the immune system. To study the
      immunogenicity of this antigen in the absence of the immunodominant repeats, the
      entire nonrepetitive region of the antigen was expressed in Escherichia coli as
      two fusion proteins with glutathione-S-transferase (GST) representing the amino
      terminal (GST-CSN) and the carboxy terminal domains (GST-CSC) of the CS antigen.
      The immunogenicity of these fusion proteins was studied in rabbits and different
      strains of mice. Antibody raised against both the CSN and CSC domains in both
      rabbits and every strain of mice recognized the native protein, as detected by
      immunofluorescence assay (IFA) using P. knowlesi sporozoites. A positive IFA
      reaction was also obtained with P. vivax sporozoites using antisera raised
      against the CSC domain. High titer antisera were raised in rabbits against both
      the domains, whereas mice showed comparatively low titers. On Western blots, mice
      showed specific response against the CSC domain. In both rabbits and mice,
      significant titers of antibodies were raised against region II, which has been
      shown to be the putative sporozoite binding site for hepatocytes in the case of
      P. falciparum.

PMID- 9025691
TI  - Immunoglobulin G reactivities to rhoptry-associated protein-1 associated with
      decreased levels of Plasmodium falciparum parasitemia in Tanzanian children.
AB  - In the Muheza region of Tanzania, an area with holoendemic malaria, the
      proportion of responders with IgG enzyme-linked immunosorbent assay reactivities
      to recombinant rhoptry-associated protein-1 (rRAP-1) as well as IgG reactivities
      to a repeat region of the acidic-basic repeat antigen (ABRA) increased with age.
      The proportion of responders with IgM reactivities to rRAP-1 increased with age
      in the first three decades. However, levels of IgG reactivities to rRAP-1 did not
      increase with age, indicating high levels of reactivities among young children.
      High P. falciparum densities were only detectable in children less than five
      years of age; in this group the proportion of IgG responders to rRAP-1 and to the
      ABRA repeat region was low but levels of IgG reactivities to rRAP-1 were
      inversely correlated with parasite density, suggesting that immune recognition of
      the antigen may be associated with resistance to infection. On the other hand,
      levels of IgG reactivities to the repeat region of ABRA increased with parasite
      densities in children 1-4 years of age. Two different profiles of IgG
      reactivities to rRAP-1 and to ABRA are detectable in young Tanzanian children and
      the Ig reactivities against rRAP-1 may be a component of the immune reactions
      restricting parasite multiplication.

PMID- 9025692
TI  - Geographic differences in the sensitivity of a polymerase chain reaction for the
      detection of Plasmodium falciparum infection.
AB  - The amplification of target DNA by highly specific probes using the polymerase
      chain reaction (PCR) provides a highly sensitive and specific method for the
      detection of malaria infection. The use the of PCR in settings with varying
      endemicity within one survey area has not been investigated intensively.
      Therefore, a cross-sectional study was conducted in the districts of Kabarole and
      Bundibugyo in western Uganda using material from three villages with different
      epidemiologic situations regarding malaria and DNA primers for a PCR that had
      shown satisfactory sensitivity and specificity in previous trials. The
      sensitivity of the PCR varied significantly (P < 0.001) in the three survey
      villages (between 63.2% and 83.9% for the primer pair K1-14-1 and between 37.9%
      and 69.9% for the primer pair MSP-1) and was highly linked to geographic
      differences and social exchanges of the inhabitants with other areas of the
      district. According to the results of this investigation, it is advisable not to
      use a single primer pair in epidemiologic field studies for the detection of
      falciparum malaria. The use of combined primer pairs and the frequent
      confirmation of the results by microscopy are recommended.

PMID- 9025693
TI  - Migration of Leishmania donovani amastigotes in the cerebrospinal fluid.
AB  - A 10-year-old boy had been suffering from kala-azar (visceral leishmaniasis) for
      two and a half years. He failed to respond to all known anti-leishmanial
      treatment regimens. Even the drastic step of splenectomy failed to cure him. In
      November 1991, he presented with symptoms of meningitis. A diagnostic lumbar
      puncture revealed leishmanial amastigotes in his cerebrospinal fluid. The patient
      was finally cured with a course of amphotericin B, a drug known to cross the
      blood-brain barrier.

PMID- 9025694
TI  - Childhood mortality during and after hospitalization in western Kenya: effect of
      malaria treatment regimens.
AB  - Plasmodium falciparum infection is an important cause of the high childhood
      mortality rates in sub-Saharan Africa. Increasingly, the contribution of P.
      falciparum-associated severe anemia to pediatric mortality is being recognized
      while the impact of chloroquine resistance on mortality has not been evaluated.
      To address the issues of pediatric mortality, causes of death among hospitalized
      children less than five years of age in western Kenya were identified using
      standardized clinical examinations and laboratory evaluations. Follow-up
      examinations were conducted to determine the child's clinical status
      posthospitalization. Of the 1,223 children admitted to Siaya District Hospital
      from March to September 1991, 293 (24%) were severely anemic (hemoglobin level <
      5.0 g/dL). There were 265 (22%) deaths; 121 (10%) occurred in-hospital and 144
      (13%) occurred out-of-hospital within eight weeks after admission; 32% of all
      deaths were associated with malaria. Treatment for malaria with chloroquine was
      associated with a 33% case fatality rate compared with 11% for children treated
      with more effective regimens (pyrimethamine/sulfa, quinine, or
      trimethoprim/sulfamethoxazole for five days). The risk of dying was associated
      with younger age (P < 0.0001) and severe anemia (relative risk [RR] = 1.52, 95%
      confidence interval [CI] = 1.22, 1.90), and was decreased by treatment with an
      effective antimalarial drug (RR = 0.33, 95% CI = 0.19, 0.65). Effective drug
      therapy for P. falciparum with regimens that are parasitocidal in areas with a
      high prevalence of severe anemia and chloroquine resistance can significantly
      improve the survival of children in Africa.

PMID- 9025695
TI  - Hunting of peridomestic rodents and consumption of their meat as possible risk
      factors for rodent-to-human transmission of Lassa virus in the Republic of
      Guinea.
AB  - In this population-based study, we correlated possible risk factors for rodent-to
      human transmission of Lassa virus with markers of Lassa fever in two different
      regions of the Republic of Guinea (Prefectures of Pita and Gueckedou). Antibody
      prevalence was 2.6% (6 of 232) in Pita compared with 14.0% (105 of 751) in
      Gueckedou, with up to 35.0% seropositivity in selected villages of the higher
      prevalence area. We observed three major risk factors in Gueckedou favoring Lassa
      virus transmission: rodent infestation was much higher, food was more often
      stored uncovered and most strikingly, peridomestic rodents were hunted as a
      protein source by 91.5% of the population as opposed to 0% in Pita. To control
      for the confounding effects of differences in rodent infestation and food
      storage, rodent consumption was analyzed as a risk factor for transmission of
      Lassa virus comparing rodent consumers (RC) and nonconsumers (NC) in Gueckedou
      only: 14.6% of RC had Lassa virus antibodies versus 7.4% of NC (P = 0.1) and
      23.0% of RC reported a history of a febrile illness with hearing loss (the most
      common sequel of Lassa fever) versus 6.1% of NC (P = 0.003).

PMID- 9025696
TI  - Prevalence of antibodies to mosquito-borne encephalitis viruses in residents of
      the Coachella Valley, California.
AB  - Sera from 19 (2.6%) and 118 (16.4%) of 719 outpatients attending clinics in the
      southeastern Coachella Valley, California during 1993 and 1994 exhibited IgG
      antibodies to western equine encephalomyelitis and St. Louis encephalitis (SLE)
      viruses, respectively, using enzyme immunoassays. However, only seven (1.0%) and
      36 (5.0%) outpatients were positive by plaque-reduction neutralization tests
      (PRNTs), and seven (1.0%) and 84 (11.7%) outpatients were positive by sera
      hemagglutination inhibition assays, respectively. None were positive for IgM
      antibodies indicative of recent infection or were diagnosed clinically with
      central nervous system disease. Prevalence of PRNT antibody to SLE increased as a
      function of patient age, but did not vary significantly in relation to years of
      residence, sex, race, postal zip code, occupation, or month of collection.

PMID- 9025697
TI  - Cocirculation of multiple hantaviruses in Texas, with characterization of the
      small (S) genome of a previously undescribed virus of cotton rats (Sigmodon
      hispidus).
AB  - An environmental and laboratory investigation was conducted after a fatal
      childhood case of hantavirus pulmonary syndrome occurred in Deaf Smith County,
      Texas in May 1995. A trapping campaign was conducted to identify possible rodent
      carriers. Six species of murid and heteromyid rodents were collected, and at
      least one hantavirus-seropositive specimen was found in each of the five murid
      species. Tissues from a selection of 11 seropositive specimens were examined by
      the polymerase chain reaction (PCR) and sequencing of viral genetic material. The
      predominant hantavirus was El Moro Canyon virus (ELMCV), which occurred in three
      of three harvest mice (Reithrodontomys megalotis) and in three of four deer mice
      (Peromyscus maniculatus) examined. Sin Nombre virus (SNV) was found in one deer
      mouse and one white-footed mouse (P. leucopus). A seropositive house mouse (Mus
      musculus) was negative by PCR. Two cotton rats (Sigmodon hispidus) were infected
      by a virus of novel genotype (Muleshoe virus [MULEV]) that bears closet
      resemblance to Bayou hantavirus. The sequence of the complete small genomic
      segment was determined for one MULEV, and high-level expression of its
      nucleocapsid protein was induced in Escherichia coli. Serologic studies indicated
      that the most likely etiologic agent in the human infection was SNV.

PMID- 9025698
TI  - Potential force of infection of human rabies transmitted by vampire bats in the
      Amazonian region of Brazil.
AB  - Human rabies transmitted by bats has acquired greater epidemiologic relevance in
      various Latin American countries, just when cases transmitted by dogs have
      decreased. Concern has been heightened by reports of increased rates of bats
      biting humans in villages in the Amazonian region of Brazil. The aim of the
      present work was to estimate the potential force of infection (per capita rate at
      which susceptible individuals acquire infection) of human rabies transmitted by
      the common vampire bat if the rabies virus were to be introduced to a colony of
      bats close to a village with a high rate of human bites. The potential force of
      infection could be then used to anticipate the size of a rabies outbreak in
      control programs. We present an estimator of potential incidence, adapted from
      models for malaria. To obtain some of the parameters for the equation, a cross
      sectional survey was conducted in Mina Nova, a village of gold prospectors in the
      Amazonian region of Brazil with high rates of bates biting humans. Bats were
      captured near dwellings and sent to The Rabies Diagnostic Laboratory at the
      Center for Control of Zoonoses (Sao Paulo, Brazil) to be examined. To estimate
      the force of infection, a hypothetical rabies outbreak among bats was simulated
      using the actual data obtained in the study area. Of 129 people interviewed,
      23.33% had been attacked by a vampire bat during the year prior to the study,
      with an average of 2.8 bites per attacked person. Males (29.41%) were attacked
      more often than females (11.36%); also, adults (29.35%) were attacked more often
      than children (8.33%). None of the 12 bats captured in Mina Nova tested positive
      for rabies, but the force of infection for a hypothetical outbreak was estimated
      to be 0.0096 per person per year. This risk represents 0.96 cases per 100 area
      residents, giving an incidence of 1.54 cases of bat-transmitted human rabies per
      year in the village of Mina Nova (160 inhabitants). The estimated risk is
      comparable with what has been observed in similar Brazilian villages.

PMID- 9025699
TI  - Biological and genetic characterization of Rickettsia sibirica strains isolated
      in the endemic area of the north Asian tick typhus.
AB  - Restriction fragment length polymorphism (RFLP) analysis of polymerase chain
      reaction-amplified gene fragments was used to characterize 24 isolates of spotted
      fever group rickettsiae previously identified as Rickettsia sibirica from their
      serologic properties. These strains were obtained in Russia between 1946 and 1991
      from humans and different species of Ixodid ticks. The RFLP analysis was
      performed using amplified DNA products obtained with a genus-specific primer pair
      derived from the R. prowazekii citrate synthase gene and two group-specific
      primer pairs from the R. rickettsii 190-kD and 120-kD surface protein antigen
      genes followed by Alu I, Pst I, and Rsa I restriction endonuclease digestions.
      Although some differences were detected in biological characteristics among the
      examined strains, only a single R. sibirica genotype was found with these
      molecular tools of identification.

PMID- 9025701
TI  - Protein anabolic action of insulin, growth hormone and insulin-like growth factor
      I.

PMID- 9025700
TI  - Seroepidemiology of Entamoeba histolytica in a slum in northeastern Brazil.
AB  - Infection with the human pathogenic parasite Entamoeba histolytica has not been
      well-characterized in northeastern Brazil. In this study, the prevalence of E.
      histolytica infection in a slum in northeastern Brazil was assayed using an
      enzyme-linked immunosorbent assay (ELISA) for antibodies against the galactose/N
      acetyl-D-galactosamine (Gal/GalNAc)-inhibitable adherence lectin of E.
      histolytica. Sera from a total of 335 individuals were examined for anti
      Gal/GalNAc lectin antibodies. The overall seropositivity was 24.7%; 29.4% of
      females and 19.4% of males were positive. Among different age groups there was a
      peak of 40% positivity in the 6-14-year-old age group. There was also familial
      clustering of seropositivity. To examine colonization, stool samples from 155
      people were examined microscopically for the presence of the parasite. Fourteen
      of 155 stools (9.0%) were identified as containing E. histolytica or
      nonpathogenic E. dispar. These 14 positive stools were analyzed with an ELISA
      that detects Gal/GalNAc lectin antigen and can distinguish between E. histolytica
      and E. dispar. Four stools (29%) were positive for E. histolytica and the
      remaining 10 were identified as E. dispar-positive. Although the overall
      colonization rate by microscopy was only 9%, with a third identified as E.
      histolytica, up to 40% of older children develop serologic evidence of having
      experienced pathogenic E. histolytica infection. The results of this study
      demonstrate that this community in northeastern Brazil is highly endemic for E.
      histolytica with infection rates similar to other developing nations.

PMID- 9025702
TI  - Islet cell autoantibodies: a family storym.

PMID- 9025703
TI  - Endothelin: culprit or bystander in Addison's disease?

PMID- 9025705
TI  - Thyroid hormone receptors are necessary but not sufficient for transcription.

PMID- 9025704
TI  - The discovery of leptin and its impact in the understanding of obesity.

PMID- 9025706
TI  - Environmental endocrinology: hidden, but potent ways of activating the estrogen
      receptor.

PMID- 9025707
TI  - Taking the message to the nucleus: MAD protein as a mediator of bone
      morphogenetic protein signaling.

PMID- 9025708
TI  - Serum leptin and weight reduction in female obesity.
AB  - Leptin, an adipocyte-derived hormone, induces a decrease in food intake and
      increases energy expenditure via hypothalamic interactions. In animal models
      obesity can be caused by leptin deficiency or by a dysfunction of the
      hypothalamic leptin receptor. Using a radioimmunoassay for the determination of
      leptin in human serum, we measured serum leptin levels in 227 otherwise healthy
      normal weight (N = 78; body mass index = 16.1-27.7 kg/m2) or obese women (N =
      149; body mass index = 27.8-56.7 kg/m2). Fifty-three subjects were followed over
      a period of 12 weeks under weight reduction (800 kcal/day) and a subgroup of 33
      for another 13 weeks after termination of the diet. Body mass index and serum
      leptin concentrations were measured longitudinally and compared to female
      controls not under diet. Under baseline conditions, log serum leptin levels were
      positively related to body mass index with a best fit using a non-linear
      regression (p < 0.001), indicating an attenuated increase in serum leptin levels
      with high body mass index. No subgroup with low serum leptin levels could be
      identified. Weight reduction induced a rapid decrease in serum leptin levels
      within the first 3 weeks to levels significantly lower than in body mass index
      matched controls under normal diet (p < 0.001). This pattern was consistent after
      6 and 12 weeks. Serum leptin levels increased again after the end of the diet but
      remained significantly lower than in the controls despite unrestricted calorie
      intake over 7 weeks. The rapid and persistent decrease in serum leptin to lower
      levels than expected from matched controls may explain the pertinent difficulties
      of obese subjects to cope with weight reduction.

PMID- 9025709
TI  - Effects of glucocorticoids and of growth hormone on serum leptin concentrations
      in man.
AB  - Recent data suggest an involvement of the ob gene and its product leptin in the
      regulation of body fat. To assess the effects of glucocorticoids and growth
      hormone (GH) on serum leptin and body fat, 30 normal subjects received
      methylprednisolone (0.5 mg.kg-1.day-1) per os for 7 days and 15 subjects received
      in addition sc injections of GH (0.15 IU.kg-1.day-1) twice daily (combination
      group). Serum leptin levels increased both in the glucocorticoid group (p < 0.02)
      and in the combination group (p < 0.002). When body fat was estimated by
      bioelectrical impedance analysis it decreased during combined treatment and
      remained unchanged in the glucocorticoid group. Plasma insulin concentrations
      increased in both groups. Resting energy expenditure (indirect calorimetry)
      increased in the combination group and remained unchanged in the glucocorticoid
      group. The finding of increased serum leptin concentrations during treatment with
      glucocorticoid and GH suggests that serum leptin is regulated by glucocorticoids,
      possibly though changes in insulin secretion, independently of changes of body
      fat mass.

PMID- 9025710
TI  - Dose-dependent effects of recombinant human growth hormone on biochemical markers
      of bone and collagen metabolism in adult growth hormone deficiency.
AB  - Administration of growth hormone (GH) to patients with growth hormone deficiency
      (GHD) has beneficial effects, but so far has been employed only empirically. We
      have, therefore, investigated the dose-dependent effect of GH on target tissue by
      studying biochemical markers of bone and collagen turnover in GHD. Then patients
      with GHD (nine males and one female aged 21-43 years, mean age 28 years)
      participated in the study. Growth hormone deficiency was defined as a peak serum
      GH response of less than 15 mU/l in two provocation tests. After a 4-week run-in
      period, the study population received increasing doses of GH at 4-week intervals
      (1, 2 and 4 U/m2). Blood samples were collected in the fasting state at 7.00 h on
      the last day of each period and assayed for serum levels of osteocalcin (S-BGP),
      bone alkaline phosphatase (B-ALP), C-terminal propeptide of type I collagen (S
      PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen
      (S-ICTP) and N-terminal propeptide of type III collagen (S-PIIINP). Following
      replacement therapy, serum insulin-like growth factor I and insulin-like growth
      factor binding protein 3 increased sequentially with time (p < 0.001 and p <
      0.001, MANOVA) and the values were elevated significantly over baseline levels
      after treatment with 1 U/m2. Serum BGP values were below normal at the start of
      the study and increased gradually following GH treatment to levels in the low
      normal range. Baseline values for serum bone alkaline phosphatase (B-ALP), PICP
      and PIIINP were within the normal range. The collagen parameters increased with
      GH replacement (p < 0.001, MANOVA) to levels above normal, whereas B-ALP stayed
      within normal limits. Serum ICTP values were elevated above the normal range at
      baseline, indicating increased bone resorption in GHD. A linear increase in
      values was observed with GH treatment (p < 0.001, MANOVA). Serum ICTP did not
      correlate significantly with the bone formative parameters but was correlated
      positively to PIIINP. The sensitivity of S-ICTP as a bone resorptive marker is
      thus questioned. In conclusion, a dose-dependent increase in markers of growth
      hormone metabolism and in biochemical markers of both bone and non-bone collagen
      synthesis was seen following incremental doses of GH in GHD.

PMID- 9025711
TI  - Free and total insulin-like growth factors and insulin-like growth factor binding
      proteins during 14 days of growth hormone administration in healthy adults.
AB  - The objective was to investigate the effect of growth hormone (GH) administration
      on circulating levels of free insulin-like growth factors (IGFs) in healthy
      adults. Eight healthy male subjects were given placebo and two doses of GH (3 and
      6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood
      samples were obtained every second day. Free IGF-I and IGF-II were determined by
      ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol
      extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3
      were measured. Serum-free and total IGF-I increased in a dose-dependent manner
      during the 14 days of GH administration. After 14 days, serum-free IGF-I values
      were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and
      3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004
      for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l
      (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p <
      0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no
      differences in the levels of free or total IGF-II during the three study periods.
      Insulin-like growth factor binding protein 1 was decreased during GH
      administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6
      IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during
      GH administration and free IGF-I increased relatively more than total IGF-I. This
      may partly be due to the decrease in IGFBP-1.

PMID- 9025712
TI  - Somatotrope responsiveness to Hexarelin, a synthetic hexapeptide, is refractory
      to the inhibitory effect of glucose in obesity.
AB  - Both spontaneous and stimulated growth hormone (GH) secretion is reduced in
      obesity, in which state insensitivity to the inhibitory effect of hyperglycemia
      also has been reported. To further investigate this point, in eight male obese
      (OB) patients (27-49 years old; body mass index = 39.5 +/- 1.7 kg/m2) we studied
      the effect of oral glucose load (100 g) on the GH response to Hexarelin (HEX, 2
      micrograms/kg iv), a synthetic hexapeptide belonging to the GH-releasing peptide
      family, which has been reported to be able to induce a marked GH rise even in
      obese patients. As a control group, six male age-matched normal subjects (NS)
      were studied (26-35 years old; body mass index = 22.3 +/- 1.5 kg/m2). In all
      subjects the GH response to growth hormone-releasing hormone (GHRH, 1
      microgram/kg iv) was also studied. Basal GH and insulin-like growth factor I (IGF
      I) levels in OB and NS were similar (0.3 +/- 0.1 vs 0.5 +/- 1.0 microgram/l and
      166.7 +/- 12.3 vs 145.4 +/- 6.9 micrograms/l, respectively). Hexarelin induced a
      clear GH rise in OB (peak: 20.0 +/- 2.9 micrograms/l; AUC: 1193.0 +/- 213.7
      micrograms.l-1.120 min-1) but this response was clearly lower (p < 0.0002) than
      that observed in NS (62.6 +/- 7.3 micrograms/l, 4587.5 +/- 614.9 micrograms.l
      1.120 min-1). The GHRH-induced GH rise was lower (p < 0.002) in OB (4.4 +/- 1.2
      micrograms/l, 331.0 +/- 95.9 micrograms.l-1.120 min-1) than that in NS (20.2 +/-
      1.9 micrograms/l, 1281.0 +/- 157.5 micrograms.l-1 .120 min-1) and both were lower
      (p < 0.05) than those induced by HEX. In NS, glucose significantly blunted the GH
      response to HEX (38.4 +/- 7.2 micrograms/l, 2236.5 +/- 514.8 micrograms.l-1.120
      min-1, p < 0.05) but failed to modify it in OB (19.4 +/- 2.7 micrograms/l, 934.5
      +/- 151.3 micrograms.l-1. 120 min-1). Plasma glucose peaks after oral glucose
      load in OB and NS were similar (164.5 +/- 9.7 vs 145.8 +/- 4.6 mg/dl). In
      conclusion, the present data demonstrate that, in contrast to normal subjects, in
      obese patients HEX has a reduced GH-releasing effect that is not inhibited by
      glucose. In OB patients as well as in normal subjects HEX releases more GH than
      GHRH. These findings strengthen the evidence that GH secretion in obesity is
      refractory either to stimulatory inputs or to the inhibitory effect of
      hyperglycemia.

PMID- 9025713
TI  - Altered blood pressure profile, autonomic neuropathy and nephropathy in insulin
      dependent diabetic patients.
AB  - To evaluate the relationship between autonomic neuropathy (AN) and nephropathy we
      measured 24-h blood pressure (BP) and overnight urinary albumin excretion (UAE)
      in 38 patients with insulin dependent diabetes mellitus (IDDM). Autonomic
      function was evaluated by the heart rate response to deep breathing. Valsalva
      maneuver, heart rate at rest and BP variation with posture. Sympathetic cutaneous
      reflex was also tested in both inferior and superior limbs. Patients with mean
      day diastolic BP (DDBP) < or = 90 mmHg without AN (N = 15) compared to 12 normal
      controls had similar BP values, but compared to those with DDBP < or = 90 mmHg
      and AN (N = 12) they had lower night diastolic BP (NDBP) (66 +/- 4.8 vs 72 +/-
      8.8 mmHg: p < 0.05) and UAE (9.8 +/- 2.3 vs 107.2 +/- 3.5 micrograms/min; p <
      0.001). No difference in DDBP was observed between these two diabetic groups (80
      +/- 3.9 vs 83 +/- 6.1 mmHg). Of the 11 patients with DDBP > 90 mmHg, only three
      were free of AN and only two of the eight with AN where free of diabetic
      nephropathy. The percentage day/night changes in systolic BP were lower in
      patients with AN (13 vs 7.9%; p < 0.05) and were inversely related to autonomic
      score, used as an index of the degree of autonomic dysfunction (r = -0.48; p <
      0.01) and to UAE (r = -0.39; p < 0.05). Furthermore, UAE correlated with
      autonomic score (r = 0.69; p < 0.0001) and with NDBP (r = 0.44; p < 0.01). Our
      results show that AN in IDDM patients is associated with a reduced nocturnal fall
      in BP and suggest a pathogenic role of autonomic dysfunction in the development
      of diabetic nephropathy, possibly favoring both BP elevation during the night and
      increases in intraglomerular pressure.

PMID- 9025714
TI  - Islet cell-specific autoantibodies in children with insulin-dependent diabetes
      mellitus and their siblings at clinical manifestation of the disease. Childhood
      Diabetes in Finland Study Group.
AB  - The aim of this work was to characterize both newly diagnosed insulin-dependent
      diabetic subjects and their siblings with positive tests for islet cell-specific
      autoantibodies (ICSAA) and to evaluate whether there is an association between
      the ICSAA levels detected in the diabetic children and siblings. We analysed 781
      probands younger than 15 years of age for islet cell antibodies (ICA) and 755 for
      insulin autoantibodies (IAA) and 610 of their 3-19-year-old non-diabetic siblings
      for ICA and IAA upon diagnosis of the proband. Islet cell antibodies were
      observed in 657 of the probands (84.1%) and IAA in 353 (46.8%). The ICA-positive
      probands were younger in age and had higher IAA levels than the ICA-negative
      probands, while the IAA-positive probands were younger and had higher levels of
      ICA than the IAA-negative probands. Islet cell antibodies were detected in 46
      (7.5%) and IAA in 16 (2.6%) siblings, and the ICA-positive siblings had higher
      IAA levels than the ICA-negative siblings. A falling trend was seen in the
      frequency of ICA > or = 20 Juvenile Diabetes Foundation units in the siblings
      with decreasing degrees of HLA identity with the index case. Infections during
      the preceding year, especially respiratory infections, increased the prevalence
      of both ICA and IAA in the diabetic children at diagnosis and the frequency of
      IAA in the siblings. There was a significant, although weak, correlation between
      the IAA levels of the probands and those of their siblings when 594 pairs were
      tested (r(s) = 0.15; p < 0.001). No association could be seen between the ICA
      levels of the probands and those of their siblings, not even when including only
      HLA-identical proband-sib pairs in the analysis. The lack of any relation between
      ICA levels in the probands and siblings supports the view that there may be
      multiple exogenous factors capable of inducing ICA formation or else a common
      factor but variable responsiveness in the index case and the sibling.

PMID- 9025715
TI  - High plasma levels of endothelin-1 in untreated Addison's disease.
AB  - The aim of this study has been to investigate the plasma endothelin-1 (ET-1)
      levels in adult patients with proven Addison's disease (AD). Plasma ET-1 levels
      were measured in 29 subjects (17 males and 12 females, aged between 20 and 54
      years): 15 of them were patients with AD and 14 were sex- and age-matched normal
      subjects, used as a control group. All patients with AD have been studied under
      basal conditions and nine of them also after 2 weeks on oral corticosteroid
      therapy (individual cortisol dosage ranging from 25 to 37.5 mg/day and 0.1 mg/day
      9 alpha-fluorohydrocortisone). Extracted plasma ET-1 was determined by a specific
      radioimmunoassay using rabbit endothelin antisera. Mean ET-1 values in the
      patients with AD were three times higher than in normal subjects (21.09 +/- 4.38
      pg/ml vs 6.72 +/- 1.74 pg/ml; p < 0.0001). Plasma ET-1 levels assayed in the
      patients with AD after 2 weeks of corticosteroid therapy were significantly
      decreased (14.47 +/- 3.7 pg/ml vs 22.8 +/- 5.2 pg/ml; -37%; p < 0.001) compared
      to values in untreated patients. However, the plasma ET-1 values obtained
      following corticosteroid therapy were still significantly higher (p < 0.001) than
      those detected in the control subjects. These results clearly indicate that
      patients with untreated AD have increased circulating ET-1 levels that may be
      reduced by short-term corticosteroid therapy.

PMID- 9025716
TI  - Acute stress attenuates but does not abolish circadian rhythmicity of serum
      thyrotrophin and growth hormone in the rat.
AB  - The effects of acute immobilization (IMO) on daily rhythms of corticosterone,
      thyroid-stimulating hormone (TSH) and growth hormone (GH) were studied in adult
      male rats. Two hours of IMO increased serum corticosterone, this increase still
      being observed 3 h after finishing stress exposure. In the dark period
      corticosterone levels did not differ in control and IMO rats, but higher levels
      were observed again in the morning of the day after. Immobilization lowered serum
      GH and TSH levels throughout the 24-h period that followed exposure to the
      stressor. Such an effect was more marked in GH than in TSH. In addition, GH, but
      not TSH, levels were found to be reduced significantly by IMO at 08.30 h of the
      next day. None the less, daily rhythms of GH and TSH were still persistent and
      roughly similar to those of control rats. The daily rhythm of food intake was
      measured in a separate experiment and it was observed, as expected, that IMO
      reduced food intake only in the dark period of the lighting cycle. It appears
      therefore unlikely that IMO-induced anorexia was the major factor responsible for
      the inhibition of GH and TSH caused by IMO at 11.00 and 19.00 h, considering that
      the amount of food intake was very low and similar in control and IMO rats during
      this period. However, anorexia might have contributed to inhibition of GH and TSH
      secretion afterwards. Thus, in a third experiment we studied the contribution of
      IMO-induced anorexia to the changes in hormone levels observed 24 h after stress
      by introducing a group of pair-fed rats. It was found that IMO, but not pair
      feeding, reduced TSH levels, whereas a similar reduction of GH was found in the
      two conditions. It might be concluded that acute stress transiently altered
      corticosterone secretion, the only long-lasting effect being a slight increase in
      its morning levels on the following stress. Immobilization also causes an
      inhibition of GH and TSH secretion in the rat that persists for several hours
      after finalization of exposure to the stressor, but daily rhythms were still
      apparent. It appears that the contribution of stress-induced anorexia is
      different in GH than in TSH. In conclusion, an acute severe stressor such as IMO,
      although modifying circulating levels of some hormones, particularly in the hours
      following exposure to the stressor, did not appear to interfere greatly with the
      expression of circadian rhythms of anterior pituitary hormones.

PMID- 9025717
TI  - Post-transcriptional induction of beta 1-adrenergic receptor by retinoic acid,
      but not triiodothyronine, in C6 glioma cells expressing thyroid hormone
      receptors.
AB  - Thyroid hormone (triiodothyronine; T3) has been shown to control the expression
      of beta 1-adrenergic receptors (beta 1-AR) in cardiac myocytes, but not in C6
      glioma cells. This cell specificity has been attributed to low expression of T3
      receptors and high expression of the c-erbA alpha 2 splice variant that
      interferes with the action of T3. To check this hypothesis we have expressed the
      c-erbA/thyroid hormone receptor (TR) alpha 1 gene in C6 glioma cells and
      investigated their response to thyroid hormone. Cells expressing TR alpha 1, but
      not wild-type cells, were responsive to T3 as shown by increased expression of
      mitochrondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3
      had no effect on beta 1-AR gene expression in either set of cells. The beta 1-AR
      mRNA concentrations were, however, altered by retinoic acid (RA) treatment.
      Retinoic acid caused a rapid up-regulation of beta 1-AR mRNA levels that was
      blocked by cycloheximide. Retinoic acid did not increase the beta 1-AR gene
      transcription rate in run-on experiments. These results indicate an indirect post
      transcriptional effect of RA. Control of beta 1-AR expression in C6 cells is also
      exerted at the translational level, because there was no correlation between mRNA
      and protein induction, as determined by radioligand binding studies. We conclude
      that lack of responsiveness of the beta 1-AR gene in C6 cells to T3 is not due to
      high expression of c-erbA alpha 2 but to undefined cell-specific factors.

PMID- 9025718
TI  - Do insulin-like growth factor binding proteins (IGFBPs) modulate the IGF-I growth
      promoting and differentiating effects in human neuroblastoma cells?
AB  - The insulin-like growth factors (IGFs) are known to stimulate both the
      proliferation and differentiation of neuroblastoma cells, but the role of the IGF
      binding proteins (IGFBPs) has not yet been established. In this study, human
      neuroblastoma SH-SY5Y cells have been treated with IGF-I and its potent analogue
      des(1-3)IGF-I alone or following preincubation with a differentiating agent such
      as 12-o-tetradecanoylphorbol-13-acetate (TPA). Cell proliferation and
      differentiation were evaluated. Conditioned medium was tested for the presence of
      IGFBPs by ligand blotting. The SH-SY5Y cell proliferation was maximally
      stimulated by des(1-3)IGF-I. The TPA-induced differentiation of SH-SY5Y,
      evaluated by assessment of cell morphology and GAP-43 expression as a biochemical
      marker of differentiation was potentiated by nanomolar concentrations of des(1
      3)IGF-I and, to a smaller extent, IGF-I Conditioned medium showed the presence of
      a major IGFBP band with an approximate molecular weight of 32.5 kD and a very
      faint band of approximately 24kD. The IGFBP immunoblotting results suggest that
      the predominant band might represent IGFBP-2. Our data represent a first
      demonstration of the presence of IGFBPs in conditioned medium of human
      neuroblastoma SH-SY5Y cells. The finding that the potent IGF-I analogue des(1
      3)IGF-I with reduced affinity for IGFBPs induce major effects on cell growth and
      differentiation suggests that the IGFBPs may play an active role in the neuronal
      response to the proliferative and differentiative effects of IGF-I.

PMID- 9025719
TI  - Effects of UK-14,304, noradrenaline, and propranolol on insulin release from
      transplanted mouse islets.
AB  - To elucidate the adrenergic responsiveness of transplanted pancreatic islets,
      normal BALB/c mice received 150 syngeneic islets under the left kidney capsule.
      After 12-40 weeks, the grafts were removed and compared with untransplanted
      islets by an in vitro perifusion technique. Noradrenaline (NA), 3 mumol/l,
      completely inhibited glucose-stimulated insulin release from untransplanted
      islets but not from grafts, whether or not the beta adrenergic blocker, L
      propranolol, was present. UK-14,304, an alpha 2-specific adrenergic agonist,
      inhibited glucose-induced insulin secretion from untransplanted islets by 80-92%
      at 0.1 or 1 mumol/l, and by 35-56% at 5-10 nmol/l. Insulin secretion from islet
      grafts was also markedly inhibited by 0.1 or 1 mumol/l, but not by 5 or 10
      nmol/l, UK-14,304. It is suggested that the diminished adrenergic inhibition of
      insulin release from islet grafts reflects an altered function of the alpha 2
      adrenoceptors on the beta-cells.

PMID- 9025721
TI  - Sympathoadrenal system and immune system in the regulation of adrenocortical
      function.

PMID- 9025722
TI  - The adrenal gland and ACTH.

PMID- 9025720
TI  - Proinflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha
      inhibit growth hormone stimulation of insulin-like growth factor I synthesis and
      growth hormone receptor mRNA levels in cultured rat liver cells.
AB  - Low levels of insulin-like growth factor I (IGF-I) in critical illness are
      observed despite increased or normal levels of growth hormone (GH). The
      mechanisms for this apparent GH resistance have not been elucidated. As many of
      the acute inflammatory responses in critical illness are mediated by the
      proinflammatory cytokines interleukin 1 beta (IL-1 beta) and tumor necrosis
      factor alpha (TNF-alpha), the present studies evaluated IL-1 beta and TNF-alpha
      effects on steady-state and GH-stimulated IGF-I synthesis and GH receptor mRNA
      levels. In rat hepatocytes in primary culture, IGF-I released into culture medium
      was determined by radioimmunoassay, and quantitative competitive polymerase chain
      reaction was used to measure IGF-I mRNA and GH receptor mRNA concentrations.
      Growth hormone increased GH receptor mRNA, IGF-I mRNA and IGF-I protein secreted
      into the culture medium. In cells not stimulated with GH, modest inhibitory
      effects of IL-1 beta on GH receptor mRNA, IGF-I mRNA and IGF-I protein levels
      were seen. However, the stimulatory effects of GH were inhibited in a dose
      dependent manner both by IL-1 beta and TNF-alpha, and at higher cytokine
      concentrations no stimulatory effects of GH were observed. Both IL-1 beta and TNF
      alpha in submaximal dose had additive inhibitory effects on IGF-I protein
      concentrations but these effects did not result in irreversible damage to cells,
      as indicated by restoration of IGF-I and GH receptor mRNA levels to normal after
      withdrawal of cytokines. In conclusion, we demonstrated that in rat hepatocytes
      in primary culture IL-1 beta and TNF-alpha inhibited GH-stimulated IGF-I
      synthesis. Diminished GH receptor mRNA concentrations in response to IL-1 beta
      and TNF-alpha indicate that low IGF-I levels during severe illness, despite high
      circulating GH levels, may at least partially be a consequence of suppression of
      hepatic GH receptor synthesis by IL-1 beta and TNF-alpha.

PMID- 9025723
TI  - Zinc for the common cold.

PMID- 9025724
TI  - Cosmetic surgery with lasers.

PMID- 9025725
TI  - Betaine for homocystinuria.

PMID- 9025726
TI  - FDA involvement in PET: help or hindrance? Part II.

PMID- 9025727
TI  - HCFA's prospective payment system for hospital outpatient services.

PMID- 9025729
TI  - Characterization of pulmonary and myocardial beta-adrenoceptors with S-1'
      [fluorine-18]fluorocarazolol.
AB  - S-1'-[18F]fluorocarazolol was administered to healthy volunteers to assess its
      potential for noninvasive measurement of regional pulmonary and myocardial beta
      adrenoceptor densities. METHODS: High-specific activity fluorocarazolol was
      intravenously injected on two separate occasions within a 1-wk interval. The
      initial injection was without pretreatment, but before the second injection, the
      volunteers either inhaled salbutamol (2 x 200 micrograms aerosol) or they
      ingested pindolol (3 x 5 mg during a 12-hr interval). Twenty-eight PET time
      frames of 31 planes were acquired over a period of 60 min after each injection.
      Blood samples were drawn and analyzed for the presence of fluorocarazolol and
      radioactive metabolites. RESULTS: Uptake of fluorocarazolol in the target tissues
      was hardly affected by salbutamol but was strongly depressed by pindolol.
      Pulmonary and myocardial tissue-to-plasma concentration ratios of fluorocarazolol
      reached plateau values of 11.6 +/- 0.6 (lungs) and 18.1 +/- 1.0 (heart) at 45-50
      min postinjection. These values were reduced to 2.0 +/- 0.4 and 2.0 +/- 0.6 after
      treatment with pindolol. CONCLUSION: These data indicate that: 1. Pulmonary and
      myocardial uptake of radioactivity after intravenous administration of S-1'
      [18F]fluorocarazolol represents radioligand binding to beta-adrenoceptors. 2.
      Pulmonary binding occurs mainly in alveoli rather than in airway smooth muscle
      under these conditions. 3. Binding kinetics do not preclude quantification of
      receptors with compartment models.

PMID- 9025728
TI  - Regulatory issues are primary focus for nuclear medicine groups.

PMID- 9025730
TI  - Fatty acid metabolic imaging with iodine-123-BMIPP for the diagnosis of coronary
      artery disease.
AB  - Iodine-123-BMIPP kinetics under high glucose levels were examined. The
      feasibility of 123I-BMIPP imaging after oral glucose loading for the detection of
      impaired fatty acid metabolism was tested in patients with coronary artery
      disease. METHODS: Fatty acid metabolic imaging with 123I-BMIPP was performed on
      29 patients in the fasting state and repeated after oral glucose loading.
      Myocardial SPECT images were obtained 20 min and 4 hr after the injection of 123I
      BMIPP. Myocardial uptake of 123I-BMIPP was calculated by a Ishii-Macintyre method
      and the clearance of 123I-BMIPP from the myocardium was determined as (early
      counts-delayed counts) x 100/early counts. Regional accumulation of 123I-BMIPP
      was scored semiquantitatively from 0 (normal) to 4 (no activity), and the sum of
      regional scores in each patient was defined as a total defect score (TDS).
      RESULTS: Total myocardial uptake of 123I-BMIPP was 1.7% +/- 0.4% in the fasting
      state and 1.6% +/- 0.3% after oral glucose loading (p < 0.05). Iodine-123-BMIPP
      clearance from the myocardium was faster after glucose loading than in the
      fasting state (27% +/- 8% versus 11% +/- 6%, p < 0.01). After glucose loading,
      123I-BMIPP clearance was faster in the ischemic myocardium (defined as areas
      perfused by stenosed coronary artery exceeding 90%) than in the nonischemic
      myocardium (33% +/- 8% versus 25% +/- 9%, p < 0.05). TDS in the ischemic
      myocardium increased from 1.8 +/- 0.4 in the fasting state to 2.1 +/- 0.4 after
      glucose loading (p < 0.01). The sensitivity for detecting coronary stenosis
      exceeding 90% increased from 55% (11/20) in the fasting state to 75% (15/20)
      after glucose loading without a loss of specificity (78%, 7/9). CONCLUSION: Oral
      glucose loading enhanced the detection of areas with impaired fatty acid
      metabolism due to coronary artery narrowing. Iodine-123-BMIPP imaging with oral
      glucose loading may be a new approach for the noninvasive diagnosis of coronary
      artery disease.

PMID- 9025731
TI  - Regional cerebral blood flow and negative/positive symptoms in 24 drug-naive
      schizophrenics.
AB  - SPECT/PET studies in schizophrenia revealed inconsistent changes of regional
      cerebral blood flow (rCBF). Frontal hyperperfusion as well as hypoperfusion are
      described. This study was undertaken to investigate the relations between rCBF,
      psychopathology according to PANSS and effects of neuroleptic therapy. METHODS:
      Twenty-four drug-naive acute patients with a first manifestation of schizophrenia
      were examined with 99mTc-HMPAO brain SPECT and assessed according to PANSS. Of
      these, 22 were controlled again after neuroleptic treatment. Following
      attenuation correction, region-to-cerebellar count ratios were obtained from 98
      irregular regions of interest drawn in all slices (6.25 mm). The ratios were
      compared to 20 control subjects, and changes lying outside of 2 s.d. were
      considered abnormal. RESULTS: In different drug-naive patients, hyperperfusion as
      well as hypoperfused patterns were found. In drug-naive patients, the seven
      subscores of positive symptoms (pos 1-7) in PANSS showed different correlations
      to rCBF: Formal thought disorders (pos 2) and grandiosity (pos 5) were positively
      correlated to bifrontal and bitemporal rCBF (r = +0.59 to +0.70). Delusional
      ideas (pos 1), hallucinatory behavior (pos 3) and suspiciousness (pos 6)
      demonstrated a negative correlation to bifrontal, cingulate, left temporal and
      left thalamic rCBF (r = -0.59 to -0.66). Stereotyped ideas (neg 7) as a negative
      symptom showed a negative correlation to left frontal, left temporal and left
      parietal rCBF (r = -0.59 to -0.65). No correlations were found between residual
      positive symptoms and rCBF after neuroleptic treatment and clinical improvement,
      but all negative symptoms (neg 1-7) had a negative correlation to bifrontal,
      bitemporal, cingulate, basal ganglia and thalamic rCBF (r = -0.59 to -0.74).
      CONCLUSION: Our results illustrate that different positive symptoms are
      accompanied by different rCBF values: some induce hyperperfusion, others
      hypoperfusion. After therapy (and reduction of positive symptoms), only negative
      symptoms correlate exclusively to hypoperfusion. This may be the crucial factor
      in explaining inconsistencies of past results in perfusion pattern in drug-naive
      schizophrenic patients.

PMID- 9025732
TI  - Asymmetry of basal ganglia perfusion in Tourette's syndrome shown by technetium
      99m-HMPAO SPECT.
AB  - Our study involved performing brain perfusion SPECT scans on Tourette's subjects
      to observe any common perfusion abnormalities involving the cerebral cortex or
      subcortical structures. METHOD: Six patients with Tourette's syndrome and nine
      normal control subjects underwent a brain SPECT study with 99mTc-HMPAO. Regions
      of interest were generated over the cerebral cortex, basal ganglia, thalamus and
      cerebellum to evaluate any relative perfusion abnormalities or asymmetry in the
      Tourette's subjects. RESULTS: Five of the six Tourette's subjects demonstrated a
      significant decrease in right basal ganglia activity which was not present in any
      of the normal control subjects. CONCLUSION: Our study suggests an etiology for
      Tourette's syndrome involving the right basal ganglia. Furthermore, brain SPECT
      may be useful in the evaluation of these patients if it proves to be sufficiently
      sensitive and specific in larger study populations.

PMID- 9025733
TI  - PET with L-[1-carbon-11]-tyrosine to visualize tumors and measure protein
      synthesis rates.
AB  - We studied the potential of PET with L-[1-11C]-tyrosine (TYR) to visualize tumors
      outside the central nervous system and to quantify their protein synthesis rates
      (PSRs). METHODS: Twenty-two patients suspected of having a malignant tumor
      underwent a PET study with TYR before biopsy. The PSR in nanomoles per milliliter
      tumor tissue per minute as well as the PSR in contralateral normal tissue,
      standardized uptake values (SUVs) and tumor-to-nontumor-ratios (T/N ratios) were
      calculated. RESULTS: Fifteen of the 16 malignancies (94%) were correctly
      visualized as a hot spot. A chondrosarcoma of the sacrum was not visualized. Of
      the six patients with benign lesions, cold spots were correctly identified in
      four (67%). A benign schwannoma and an intramuscular hemangioma of the forearm
      were visualized as hot spots. PSR in tumor tissue was higher than in the
      corresponding contralateral normal tissues. PSR and SUV in malignant tumors were
      higher than in benign tumors. CONCLUSION: TYR appears to be a good tracer for
      imaging malignancies. The PSR, which was higher in malignant tumors than in
      normal tissue and the studied benign lesions, could be quantified and correlated
      with the SUV.

PMID- 9025734
TI  - Incremental prognostic value of thallium reinjection after stress-redistribution
      imaging in patients with previous myocardial infarction and left ventricular
      dysfunction.
AB  - This study evaluated the incremental prognostic value of 201TI reinjection
      imaging over clinical, exercise and thallium stress-redistribution data in
      patients with previous myocardial infarction and left ventricular dysfunction.
      METHODS: Thallium-201 reinjection after stress-redistribution SPECT was performed
      in 104 consecutive patients with a first Q-wave myocardial infarction (> 8 wk)
      and left ventricular ejection fraction < or = 40%. Follow-up data (mean 22 mo)
      were available for 98 patients; 16 patients underwent early revascularization
      procedures within 3 mo after exercise testing and were not considered for the
      analysis. RESULTS: During follow-up there were 13 hard events (cardiac death and
      myocardial infarction) and 11 soft events (coronary revascularization procedures
      > 3 mo after thallium imaging). With multivariate Cox regression analysis, the
      sum of defects at stress-redistribution imaging that were reversible or moderate
      irreversible after reinjection was a powerful predictor of subsequent events. The
      addition of thallium reinjection imaging data significantly improved the
      prognostic power of clinical, exercise and stress-redistribution data for the
      occurrence of hard events (p < 0.01). CONCLUSION: In patients with previous
      myocardial infarction and left ventricular dysfunction, thallium reinjection
      imaging provides incremental prognostic information over those obtained from
      conventional stress-redistribution imaging.

PMID- 9025735
TI  - Exercise-rest same-day SPECT sestamibi imaging to detect coronary artery disease.
AB  - This study examined the results of exercise-rest same-day SPECT protocol in 193
      patients, of whom 132 had coronary artery disease (CAD) by angiography (> or =
      50% diameter stenosis), and 61 had a low pretest probability of CAD. METHODS: The
      rest study was combined with first-pass radionuclide angiography using the
      multicrystal gamma camera in 72 patients. RESULTS: The sensitivity of SPECT was
      76% (25/33 patients) in patients with one-vessel, 84% in patients with two-vessel
      (38/45) and 98% in patients with three-vessel CAD (53/54) (P = 0.01 versus one-
      or two-vessel CAD). The sensitivity of SPECT in patients with CAD was higher than
      ST depression (88% versus 28%, P = 0.001). The exercise was submaximal in 53
      patients (40%). The perfusion defects were reversible (complete or partial) in 80
      patients and fixed in 36 patients. The left ventricular ejection fraction was 50
      +/- 12% in patients with reversible defects (n = 44) and 39 +/- 9% in patients
      with fixed defects (n:19) (P = 0.0004). The normalcy rate in subjects with a low
      pretest probability of CAD was 95% (53 of 61 subjects). CONCLUSION: The exercise
      rest same-day sestamibi protocol provides high diagnostic accuracy for CAD
      detection. The protocol may eliminate the need for rest studies in patients with
      normal exercise images, help improve laboratory throughput and lower costs.

PMID- 9025736
TI  - Effect of haloperidol dose on iodine-123-IBZM brain SPECT imaging in
      schizophrenic patients.
AB  - Studies have suggested that antipsychotic drug therapy with haloperidol in
      schizophrenic patients requires an optimal dose that blocks the brain dopamine D2
      receptors. We evaluated the effect of different doses of haloperidol on D2
      receptor occupancy in schizophrenia. METHODS: Three normal subjects and three
      patients with acute schizophrenia had serial brain SPECT imaging studies (every 5
      min) for 3 hr following the injection of [123I]IBZM. The patients had IBZM
      studies off medication and at different doses (1-10 mg) of haloperidol. RESULTS:
      The basal ganglia (BG) were well visualized in normals and in schizophrenics off
      medication. After haloperidol therapy, SPECT images showed qualitatively
      diminished activity in the basal ganglia. ROIs were drawn over the basal ganglia
      and cerebellum (CE). The results were expressed as BG/CE ratios. At 2 hr
      postinjection of IBZM, the mean BG/CE ratio in normals was 1.75 +/- 0.025. In
      schizophrenics, the BG/CE ratio off medication was 1.54 +/- 0.12. The BC/CE ratio
      showed an inverse relationship to haloperidol dose; 1.46 at 1 mg, 1.25 at 4 mg
      and 1.05 at 10 mg, respectively. CONCLUSION: These results demonstrate that IBZM
      brain SPECT imaging studies are potentially useful to relate the antipsychotic
      drug D2 receptor occupancy with the administered dose in schizophrenic patients
      and may ultimately help optimize antipsychotic treatment.

PMID- 9025737
TI  - Accelerated gastric emptying in hypertensive subjects.
AB  - The phenomenon of accelerated gastric emptying has been previously reported in
      two conditions that are considered to be part of the insulin-resistance syndrome:
      namely, noninsulin-dependent diabetes (NIDDM) and increased body mass index
      (BMI). No previous studies have assessed the rate of gastric emptying in patients
      with essential hypertension, another disease considered to be part of the insulin
      resistance syndrome. METHODS: Scintigraphic gastric emptying studies were
      performed on nine hypertensive subjects and on nine sex-, age-, ethnicity and BMI
      matched controls. RESULTS: Subjects with hypertension had significantly more
      rapid gastric half-emptying times (gastric T50) (40.0 +/- 6.9 min versus 56.6 +/-
      3.7 min, p = 0.02) than controls. There was an inverse relationship between
      average glucose during the first 30 min and 60 min of the oral glucose tolerance
      test with the gastric half-emptying time (Spearman rank correlation coefficient
      rs = -0.64, p = 0.0045 and rs = -0.48, p = 0.0428, respectively). CONCLUSION: The
      occurrence of accelerated gastric emptying in hypertensive subjects, in addition
      to that previously reported in subjects with NIDDM or increased BMI, suggests the
      possibility that accelerated gastric emptying may be a common finding in insulin
      resistant states.

PMID- 9025738
TI  - Photopenia in chronic vertebral osteomyelitis with technetium-99m-antigranulocyte
      antibody (BW 250/183).
AB  - Photon-deficient areas in 99mTc/111 in white blood cell (WBC) images for
      diagnosing vertebral osteomyelitis have been published often. This study
      retrospectively evaluated whether the use of 99mTc-labeled monoclonal
      antigranulocyte antibodies (BW 250/183) is superior to WBC and whether it offers
      higher specificity. METHODS: The study included 81 patients (46 men, 35 women;
      mean age 55 +/- 2 yr; from 1989 to 1995) with clinically suspected vertebral
      osteomyelitis who underwent scintigraphic imaging after intravenous injection of
      555 MBq 99mTc-labeled monoclonal antigranulocyte antibodies. Forty patients
      suffered from osteomyelitis (20 men, 20 women; mean age 56 +/- 6 yr), 6 patients
      had metastases, 28 patients had spondylosis and disk herniation and 5 patients
      vertebral compression fractures. Diagnosis was not histologically verified in 2
      patients. Planar imaging was performed at 4 and 24 hr postinjection. Histology of
      osteomyelitis was available in 30 patients, clinical follow-up in 10 patients.
      Visual uptake scores and quantitative uptake scores of the suspected areas were
      calculated. The results were compared to a semiquantitative histological score
      (high, medium, low grade) as well as to the scintigraphic scores. RESULTS:
      Scintigraphy showed photopenia in all patients with histologically proven
      vertebral osteomyelitis, independent of the grade of infection. A quantitative
      evaluation of 4 and 24 hr postinjection demonstrated a 58% increase of the uptake
      score in cases of histologically proven high-grade infections. This increase was
      seen predominantly in the thoracic spine but not in lumbar spine. All nonosseous
      paravertebral abscesses (n = 2) showed positive images and an increasing uptake
      over 24 hr. CONCLUSION: Paravertebral soft tissue infections can be
      differentiated excellently, whereas vertebral osteomyelitis, vertebral tumors or
      fractures can be localized, but no differentiation is possible.

PMID- 9025739
TI  - Changes in results of Gallium-67-citrate scanning after interferon therapy for
      chronic hepatitis C.
AB  - Gallium-67 scanning is useful for early diagnosis and grading of interstitial
      lung disease. In a study of the side effects of interferon (IFN) on the lungs of
      patients with chronic hepatitis C, we performed 67Ga scanning before and after
      IFN therapy. METHODS: The 66 subjects who underwent at least one scanning, before
      IFN therapy, were 8 patients with chronic persistent hepatitis (CPH), 21 with
      chronic aggressive hepatitis 2A (CAH-2A), 25 with chronic aggressive hepatitis 2B
      (CAH-2B) and 12 with cirrhosis. All had underlying hepatitis C viral infection.
      Of those patients, 20 were examined again within 1 mo after IFN therapy. Patients
      received an intravenous injection of 340 MBq 67Ga-citrate and were imaged 72 hr
      later. ROIs were established for anterior views of the lungs (Lu), liver (Li) and
      soft tissue of the upper arm as background (B). The counts per unit size of each
      region of interest were used in calculation of the ratios Lu/B and Li/B. RESULTS:
      The medians of Lu/B were 2.46 in CPH, 2.56 in CAH-2A, 2.50 in CAH-2B and 2.47 in
      cirrhosis. These differences were not statistically significant. The medians of
      Li/B were 6.42 in CPH, 6.14 in CAH-2A, 5.11 in CAH-2B and 4.03 in cirrhosis. The
      differences between the median Li/B of cirrhotic patients and the medians for
      patients with CPH, CAH-2A and CAH-2B were significant. After therapy, Lu/B was
      higher than before in 16 of the 20 patients and lower in the four other patients;
      the overall rise was significant (Wilcoxon rank-sum test). Li/B was higher than
      before in 11 of the 20 patients and lower in the nine other patients. CONCLUSION:
      IFN caused uptake of the radionuclide to increase in most patients. This method
      showed changes in the accumulation of 67Ga-citrate that could have been missed if
      the results had been inspected by eye. IFN can cause interstitial lung disease,
      but unlike other drugs with this side effect, the onset seems to be gradual
      enough to be detected quantitatively by 67Ga scanning.

PMID- 9025740
TI  - Detection of postoperative deep-venous thrombosis using technetium-99m-labeled
      tissue plasminogen activator.
AB  - The current noninvasive methods of deep-venous thrombosis (DVT) detection in the
      asymptomatic patient are sufficiently inaccurate so as to preclude their routine
      use. This present study reports the accuracy of scintigraphic scanning with 99mTc
      rt-PA in asymptomatic postoperative patients using contrast venography as the
      gold standard. METHODS: Fifty-three consecutive postarthroplasty patients (30
      THR, 23 TKR) (16 women, 37 men; mean age 71 yr; range 52-85 yr) underwent
      scintigraphic scanning with 99mTc-rt-PA and contrast venography, on the operated
      leg, in order to assess the accuracy of this new technique in these asymptomatic
      patients. RESULTS: Eighty-four segments were of diagnostic quality on contrast
      venography. Of the 15 thrombosed segments, 14 had positive scans. In the 69
      nonthrombosed segments, 63 had negative scans. Thus, scintigraphic scanning with
      99mTc-rt-PA had a sensitivity of 93% and a specificity of 91%. CONCLUSION: This
      study demonstrated that scintigraphic scanning with modified 99mTc-rt-PA is
      accurate in the detection of DVT in patients undergoing total hip or total knee
      arthroplasty.

PMID- 9025741
TI  - The role of thallium-201 uptake and retention in intracranial tumors after
      radiotherapy.
AB  - This study prospectively assessed the diagnostic accuracy and prognostic value of
      201TI uptake and retention in primary and metastatic intracranial tumors treated
      by conventional radiotherapy and/or radiosurgery. METHODS: An initial 201TI study
      (early and delayed images), was obtained in 60 postsurgical patients, 6-12 wk
      after radiotherapy or radiosurgery. Repeat imaging was performed as clinically
      warranted. Tumor-to-background count ratios and a retention index (RI) were
      calculated for all lesions. RESULTS: Abnormally increased 201TI uptake was
      observed in 40 of 60 patients. In all patients with positive results, the
      diagnosis of residual tumor was confirmed at biopsy or by clinical follow-up. In
      20 of 60 patients, no abnormal 201TI uptake was observed, despite findings on CT
      and/or MRI scans that were suspicious for tumor. Ten of the negative 201TI
      studies were confirmed as true-negatives by the clinical course and by resolution
      of CT/MRI abnormalities. The remaining 10 negative SPECT studies ultimately
      proved to be false-negatives: six of these patients had lesions < 1 cm in maximum
      diameter, one patient had a large metastatic choriocarcinoma; and three patients
      had low-grade astrocytomas > 2 cm in minimum diameter. Tumor-to-background ratio
      of 201TI uptake did not distinguish between tumor type, or predict clinical
      outcome. The RI of 201TI was significantly higher for metastatic melanoma than
      for other tumor metastases. It demonstrated reasonably good correlation with
      clinical outcome: 6/7 patients with eventual tumor regression showed a decrease
      in RI on follow-up examination, and 4/5 patients with eventual tumor progression
      had an increase in RI. CONCLUSION: Thallium-201 brain SPECT appears to be a
      useful noninvasive imaging technique in patients irradiated for intracranial
      tumors. Thallium-201 scintigraphy has very high specificity (100% in this cohort)
      for detecting viable residual tumor. False-negative findings may occur.
      Quantitative analysis of 201TI uptake has limited diagnostic and prognostic
      significance, but changes in 201TI retention after radiation therapy seems to
      have prognostic value.

PMID- 9025742
TI  - Technetium-99m-sestamibi scanning in recurrent medullary thyroid carcinoma.
AB  - The presence of recurrent medullary thyroid carcinoma (MTC) can be detected early
      by measurement of serum calcitonin levels, but the localization of recurrent
      tumors is often difficult. METHODS: We compared 99mTc-sestamibi scans with
      computed tomographic (CT) scans in 10 patients with recurrent MTC, who had basal
      serum calcitonin values ranging from 220-61800 ng/liter. Two patients
      additionally had bone scans performed because of the clinical suspicion of bone
      metastases. RESULTS: Seven of the 10 patients had at least one site of abnormal
      99mTc-sestamibi uptake, and all of these patients had basal serum calcitonin
      values > 6000 ng/liter. Only five of the 10 patients had abnormal CT scans.
      Technetium-99m-sestamibi scans detected 22 abnormal sites in the soft tissues of
      the neck and chest, while CT scans detected only 11 lesions in the neck and
      chest. Five of these sestamibi positive sites (in the neck and mediastinum of one
      patient) were confirmed histologically to represent MTC. When imaging the liver,
      CT scans detected 47 lesions in three patients while 99mTc-sestamibi scans
      detected none. One of these liver lesions was confirmed as MTC histologically.
      When imaging bone in two of the patients, the bone scans detected 17 abnormal
      sites, while 99mTc-sestamibi scans detected six abnormal sites. CONCLUSION:
      Technetium-99m-sestamibi scans complement CT and bone scans in the localization
      of recurrent MTC in patients with extremely high calcitonin levels. Technetium
      99m-sestamibi scans are more sensitive than CT scans in the assessment of the
      soft tissues of the neck and chest, but CT is more appropriate for imaging
      hepatic lesions and bone scans are better for imaging bone lesions. Technetium
      99m-sestamibi scans are unlikely to be abnormal in patients with only mild
      elevation of calcitonin.

PMID- 9025743
TI  - Tin-117m(4+)DTPA: pharmacokinetics and imaging characteristics in patients with
      metastatic bone pain.
AB  - Biokinetics and imaging characteristics of 117mSn(4+)DTPA have been studied in
      patients with metastatic bone pain. METHODS: Seventeen patients with bone pain
      due to metastasis were given three dose levels: 180 microCi/kg (6.66 MBq/kg), 229
      microCi/kg (8.47 MBq/kg) and 285 microCi/kg (10.55 MBq/kg) body weight. Periodic
      blood and daily urine samples were collected for 14 days to measure percent
      injected activity retained in blood and that excreted in urine. Simultaneous
      anterior and posterior view whole-body images were obtained under identical scan
      settings at 1, 3.5 and 24 hr and on Days 3 and 7 and between 4-6 and 8-10 wk
      postinjection. The total body retention was calculated using the geometric mean
      counts. RESULTS: After intravenous injection, the total body clearance of
      117mSn(4+)DTPA shows two components: a soft-tissue component and a bone
      component. The soft-tissue component accounts for 22.4% of the dose and consists
      of four subcomponents with an average biologic clearance half-time of 1.45 days
      (range 0.1-3.2 days). The bone component accounting for the remaining 77.6% of
      the dose shows no biologic clearance. A mean 22.4% of the dose is excreted in
      urine in 14 days; 11.4% within 24 hr. The uptake pattern appears similar to that
      of 99mTc-MDP. Peak uptake is observed in normal bone by 24 hr and metastatic
      lesions by 3-7 days. Pain palliation was observed with all three doses levels.
      CONCLUSION: Among the four potential bone pain palliation radionuclides,
      117mSn(4+)DTPA demonstrates the highest bone uptake and retention. Some
      biokinetic and radionuclidic features of 117mSn(4+)DTPA are similar to other
      agents, but many features are different and unique and may make it an ideal bone
      pain palliation agent. Double-blind comparative studies are needed to determine
      its exact role in bone pain palliation.

PMID- 9025745
TI  - The incremental value of diagnostic tests.

PMID- 9025744
TI  - Scintigraphic assessment of therapeutic success in aldosteronomas treated by
      transcatheter arterial embolization using absolute ethanol.
AB  - Adrenocortical scintigraphy was examined as an indicator of therapeutic success
      in aldosteronomas treated by transcatheter arterial embolization (TAE) with
      absolute ethanol (AE). METHODS: Adrenocortical scintigraphy was performed 7 days
      after intravenous injection of 37 MBq 131I-6-beta-iodomethyl-19-norcholesterol
      before and after TAE. Complete or incomplete therapeutic success was determined
      by periodic measurements of the levels of plasma aldosterone and correlated with
      the scintigraphic results. RESULTS: The aldosteronoma was visualized as a hot
      nodule in nine patients and a warm nodule in one patient before TAE. Scintigraphy
      showed a hot, residual hot or warm nodule on seven occasions (six occasions after
      the first TAE and one occasion after the second TAE) when the techniques were
      incompletely successful and disappearance on seven occasions when success was
      achieved (three occasions after the first TAE and one occasion after the second
      TAE). Of the seven occasions when TAE was unsuccessful, four patients received
      the second or third TAE to result in complete destruction of the aldosteronoma;
      three patients underwent unilateral adrenalectomy. CONCLUSION: Adrenocortical
      scintigraphy can correctly predict the effect of TAE on aldosteronomas and is a
      valuable indicator for decisions on the necessity of repeated TAE or
      adrenalectomy.

PMID- 9025746
TI  - Evaluation of therapy response in children with untreated malignant lymphomas
      using technetium-99m-sestamibi.
AB  - The aim of this study was to investigate the relationship between 99mTc-sestamibi
      accumulation in tumors and response to chemotherapy in children with untreated
      malignant lymphomas. METHODS: Twenty-four children with malignant lymphoma (16
      with Hodgkin's disease and 8 with non-Hodgkin's lymphoma) were studied with 201Tl
      and then with 99mTc-sestamibi scintigraphy before any therapeutic intervention.
      Visual and quantitative interpretation of 201Tl and 99mTc-sestamibi scans were
      performed. Visual uptake scores > or = 2+ were considered positive studies for
      201Tl and 99mTc-sestamibi scintigraphy. Remission rates were evaluated at the end
      of induction therapy; patients were then followed clinically for 1-2 yr. RESULTS:
      All 17 patients who had positive 99mTc-sestamibi scans subsequently had a
      complete response to chemotherapy; all seven patients who had negative 99mTc
      sestamibi scans subsequently had partial or no response to chemotherapy,
      irrespective of the lymphoma type. The mean tumor-to-background ratios of
      patients with complete response and with partial or no response were 1.395 +/-
      0.2 and 1.031 +/- 0.05 (p = 0.0002), respectively. Thallium-201 scintigraphy
      results were not related to the response to chemotherapy. CONCLUSION: Technetium
      99m-sestamibi scintigraphy can provide information predicting the response to
      chemotherapy in patients with malignant lymphoma.

PMID- 9025747
TI  - Scintigraphy of posterior tibial tendinitis.
AB  - Our goal was to describe the typical scintigraphic pattern of posterior tibial
      tendinitis. METHODS: Bone scintigraphs were reviewed to study the scintigraphic
      characteristics of posterior tibial tendinitis in nine patients with posterior
      tibial tendinitis related to generalized rheumatic disease and in eight patients
      with isolated posterior tibial tendinitis. RESULTS: The scintigraphic pattern of
      posterior tibial tendinitis is elongated increased uptake in the blood flow and
      blood-pool phase along the anatomical course of the tibialis posterior tendon at
      the medial aspect of the ankle (malleolus region). Static images demonstrate
      increased focal abnormal uptake at the medial malleolus and in the navicular
      bone. CONCLUSION: Bone scintigraphy depicts a characteristic pattern of posterior
      tibial tendinitis. It is useful for the early diagnosis of idiopathic- or
      rheumatic-related posterior tibial tendinitis.

PMID- 9025748
TI  - Myocardial necrosis by electrocution: evaluation of noninvasive methods.
AB  - We present the case of a young man who suffered severe anteroapical myocardial
      necrosis caused by electrocution. In addition to the enzymatic and
      electrocardiographic changes suggesting necrosis, a clear positive segmental
      image on 99mTc-pyrophosphate scintigraphy and a defect on a 201Tl SPECT scan at
      rest were also found. Although these tests were indicative of extensive
      anteroapical transmural myocardial necrosis, the echocardiographic study only
      revealed mild anteroapical hypokinesia.

PMID- 9025749
TI  - ECT treatment and cerebral perfusion in Catatonia.
AB  - A 40-yr-old woman with a diagnosis of schizoaffective disorder developed
      catatonia in the context of a depressive episode. A dramatic decrease in
      perfusion of the inferior frontal, posterior temporal and parietal lobes
      bilaterally and in posterior frontal lobes corresponding to the motor cortices
      was noted on the 99mTc-HMPAO SPECT scan obtained in the acute phase. The most
      dramatic decreases compared to normal control subjects were observed in the left
      parietal and left motor cortices. The patient was treated with a five-treatment
      course of electroconvulsive therapy (ECT), which resulted in a complete
      resolution of catatonia and some resolution of her symptoms of depression. The
      repeat HMPAO-SPECT scan showed improved perfusion in all areas. The most dramatic
      increases occurred in the left parietal and left motor cortices. Decreased
      perfusion in motor and parietal cortices could be state-specific to catatonia.
      Thus, SPECT imaging may be a useful method for monitoring catatonia treatment
      response.

PMID- 9025750
TI  - Identification of severe right ventricular dysfunction by technetium-99m
      sestamibi gated SPECT imaging.
AB  - An 84-yr-old man with previous anterior wall myocardial infarction presented with
      shortness of breath and palpitations. His symptoms were attributed to myocardial
      ischemia, and he was referred for a stress 99mTc-sestamibi SPECT imaging study
      with gating. The images showed minimal left ventricular ischemia, but a dilated
      and hypokinetic right ventricle suggested pulmonary pathology as the probable
      etiology of his presenting symptoms. A subsequent ventilation perfusion study was
      consistent with the diagnosis of multiple pulmonary emboli. Thus, 99mTc-sestamibi
      SPECT imaging with gating provides information about right ventricular perfusion
      and function, enhancing the clinical utility of stress myocardial perfusion
      imaging.

PMID- 9025752
TI  - Graves' disease triggered by autoinfarction of an autonomously functioning
      thyroid adenoma.
AB  - A patient whose nontoxic autonomously functioning thyroid adenoma had been stable
      for at least 3 yr developed enlargement of the nodule and hyperthyroidism. It was
      assumed the hyperthyroidism was caused by evolving toxicity in the autonomous
      adenoma, but imaging showed the nodule had undergone infarction and the
      hyperthyroidism was secondary to Graves' disease. This case demonstrates the
      necessity of thyroid imaging in patients with nontoxic autonomously functioning
      thyroid adenomas when there is a change in nodule size or thyroid function which
      requires treatment.

PMID- 9025751
TI  - Regression of advanced refractory ovarian cancer treated with iodine-131-labeled
      anti-CEA monoclonal antibody.
AB  - Advanced chemotherapy-resistant ovarian cancer has a poor prognosis, thus
      requiring new therapeutic modalities. A complete clinical remission, using two
      cycles of 131I-labeled murine MN-14 anti-CEA monoclonal antibody (MAb), given
      intravenously, is reported in a patient with advanced ovarian cancer refractory
      to paclitaxel (Taxol) therapy. The patient first received radioimmunotherapy with
      approximately 74 mCi 131I-MN-14 IgG, followed 4 mo later by a similar dose of
      radiolabeled MAb. A partial remission was seen by CT 1 mo after the first
      radioimmunotherapy, and a further objective response was documented after the
      second radioimmunotherapy. CT scans performed 6 and 11 mo after the second
      radioimmunotherapy showed stable and minimal residual changes. However, a whole
      body PET scan with [18F]fluorodeoxyglucose (FDG-PET) was negative in these
      regions. The CA-125 also decreased to only 13 U/ml, compared to the baseline
      value of 7700 U/ml. Based on CT, FDG-PET, serum CA-125 and physical exam, the
      patient was in complete clinical remission for 8 mo when the CA-125 levels rose.
      CT also showed a new suspicious lesion, presumably a peritoneal implant. No
      toxicity was seen after the first injection, and only Grade 1 thrombocytopenia
      and Grade 2 leukopenia developed after the second injection, both reversing
      within 6 wk. This is a report of a complete clinical remission with radiolabeled
      anti-CEA antibodies in a patient with chemotherapy-refractive metastatic ovarian
      cancer.

PMID- 9025753
TI  - Technetium-99m-MDP uptake in hilar lymph nodes in sarcoidosis.
AB  - We describe a patient with unexplained hypercalcemia who under went bone
      scintigraphy, which demonstrated marked tracer uptake within the hilar lymph
      nodes. The pattern strongly suggested sarcoidosis, which was subsequently
      confirmed by bronchoscopy-directed biopsy.

PMID- 9025755
TI  - Kinetics of technetium-99m-teboroxime in reperfused nonviable myocardium.
AB  - This study evaluates 99mTc-teboroxime uptake and clearance kinetics in reperfused
      infarcted myocardium. METHODS: In 47 isolated buffer perfused rat hearts, 17 had
      normal flow (Control), 13 had 30 min of no flow followed by reflow (Noflow30) and
      11 had 60 min of no flow followed by reflow (Noflow60). A 1-hr uptake phase was
      begun by normally perfusing all 41 hearts with 99mTc-teboroxime-doped buffer.
      After uptake, a 1-hr clearance phase was begun by switching to a 99mTc-teboroxime
      free buffer. Technetium-99m activity was monitored with a Nal probe. Triton X
      100, a membrane detergent, was given after tracer loading to six additional
      hearts. RESULTS: Control and Noflow30 hearts showed near linear and rapid uptake,
      while Noflow60 hearts showed curvilinear and significantly less uptake than
      predicted. All three of these groups showed biexponential clearance. Early t1/2
      was not significantly different for the three groups (Control = 6.3 +/- 1.9 sem
      min, Noflow30 = 5.4 +/- 1.3 min, Noflow60 = 8.9 +/- 2.8 min). Late t1/2 was
      significantly shorter for Noflow30 (52.3 +/- 5.3 min) and the Noflow60 (50.9 +/-
      4.3 min), compared to the Control hearts (74.1 +/- 6.6 min, p < 0.05). One-hour
      fractional clearances were significantly greater for the Noflow30 and Noflow60
      hearts (0.65 +/- 0.01 and 0.65 +/- 0.01, respectively) compared to the Controls
      (0.55 +/- 0.01, p < 0.05). In hearts given Triton X-100, there was a markedly
      increased fractional clearance of 0.96 +/- 0.01 (p < 0.01 compared to Controls).
      Electron microscopy showed evidence of mild injury in the Noflow30 hearts, more
      extensive damage in the Noflow60 hearts and severe irreversible injury in Triton
      X-100 hearts. CONCLUSION: Myocardial 99mTc-teboroxime uptake and clearance
      kinetics are significantly altered in mildly and moderately injured reperfused
      myocardium. Technetium-99m-teboroxime clearance is markedly accelerated in the
      setting of overt damage to cell and organelle membranes induced by Triton X-100.

PMID- 9025754
TI  - Potassium and thallium uptake in dog myocardium.
AB  - We sought to ascertain the rates and mechanisms of uptake of markers for regional
      myocardial blood flows. METHODS: The rates of exchange of potassium and thallium
      across capillary walls and cell membranes in isolated blood-perfused dog hearts
      were estimated from multiple indicator dilution curves recorded for 131I-albumin,
      42K and 201Tl from the coronary sinus outflow following injection into arterial
      inflow. Analysis involved fitting the observed dilution curves with a model
      composed of a capillary-interstitial fluid-cell exchange region and nonexchanging
      larger vessels. RESULTS: Capillary permeability surface products (PSc) for
      potassium and thallium were similar, 0.82 +/- 0.33 (mean +/- s.d., n = 19) and
      0.87 +/- 0.32 ml min-1 g-1 (n = 24) with a ratio for simultaneous pairs of 1.02
      +/- 0.27 (n = 19). For the myocardial cells, PSpc averaged 3.7 +/- 3.1 ml min-1 g
      1 (n = 19) for K+ and 9.5 +/- 3.9 (n = 24) for Tl+; the ratio of potassium to
      thallium averaged 0.40 +/- 0.19 (n = 18), thereby omitting a single high value
      for potassium. This high cellular influx for thallium is interpreted as due to
      its passage through ionic channels for both Na+ and K+. CONCLUSION: The high
      permeabilities and large volumes of distribution make thallium and potassium
      among the best ionic deposition markers for regional flow. Their utility for this
      purpose is compromised by significant capillary barrier limitation retarding
      uptake; so regional flow is underestimated modestly in high-flow regions
      particularly.

PMID- 9025756
TI  - Assessment of cancer recurrence in residual tumors after fractionated
      radiotherapy: a comparison of fluorodeoxyglucose, L-methionine and thymidine.
AB  - This study evaluates the midterm follow-up of tumor and normal tissue uptake of
      deoxyglucose, thymidine and methionine after fractionated radiotherapy to assess
      cancer recurrence in residual tumors. METHODS: AH109A tumor-burdened rats were
      treated with one to eight doses of 5Gy 60Co radiation. Tissue distribution study
      with 18F-FDG, 3H-thymidine and 14C-methionine, double-tracer autoradiography with
      18F-FDG and 14C-methionine, and single-tracer autoradiography with 14C-labeled
      deoxyglucose, thymidine and methionine were performed 6 days after the end of
      therapy. RESULTS: Dose response study shows a significant decrease of tumor
      uptake of all tracers after two and more doses, even in the case of later
      recurrence. Whereas 3H-Thd and 14C-Met tumor uptake was similar to that of normal
      muscle, 18F-FDG tumor uptake remains higher than that of muscle, even in the case
      of complete tumor cure. The irradiated muscle shows a higher 18F-FDG uptake than
      the nonirradiated muscle. Autoradiography after eight doses (100% tumor cure)
      reveals elevated 14C-DG tumor uptake to be ascribable to nonmalignant cellular
      elements, in particular to a macrophage layer at the rim of necrotic areas.
      Autoradiography after four and six doses (33% and 57% tumor cure) shows the
      highest methionine and thymidine uptake in viable cancer cells, whereas
      deoxyglucose uptake did not differ between viable cancer cells and macrophages.
      CONCLUSION: To detect and differentiate viable cancer cells in a residual tumor
      mass after radiotherapy, PET using 11C-methionine or 11C-thymidine may have some
      advantages over 18F-FDG, especially if the residual tumor includes larger areas
      of necrosis.

PMID- 9025757
TI  - Monitoring gene therapy with herpes simplex virus thymidine kinase in hepatoma
      cells: uptake of specific substrates.
AB  - This study investigates the application of PET with specific substrates for the
      assessment of enzyme activity after transfer of the herpes simplex virus
      thymidine kinase (HSV-tk) gene. METHODS: After transfection of a rat hepatoma
      cell line with a retroviral vector containing the HSV-tk gene, different clones
      were established by G418 selection. Uptake measurements were performed up to 48
      hr in a TK-expressing cell line and in a control cell line using thymidine (TdR;
      measured under therapy conditions), fluorodeoxycytidine (FdCyt) and ganciclovir
      (GCV). Additionally, bystander experiments and inhibition/competition studies
      were done. RESULTS: In TK-expressing cells GCV treatment caused an increased (up
      to 250%) TdR uptake in the acid-soluble fraction and a decrease to 5.5% in the
      acid-insoluble fraction. The FdCyt uptake was higher in the TK-expressing cells
      than in controls with a maximum after 4 hr (12-fold and 3-fold higher in the acid
      insoluble and acid-soluble fraction). GCV accumulated up to 180-fold more in the
      acid-insoluble and 26-fold more in the acid-soluble fraction. GCV uptake occurred
      mainly by the nucleoside transport systems. Bystander experiments revealed a
      relation between growth inhibition or GCV uptake and the amount of TK-expressing
      cells. GCV uptake and growth inhibition were correlated with r = 0.96.
      CONCLUSION: Assessment of GCV accumulation may serve as an indicator of the
      enzyme activity and of therapy outcome. TdR may be useful to measure therapy
      effects on DNA synthesis, whereas the potential of FdCyt has to be investigated
      in further studies.

PMID- 9025758
TI  - Technetium-99m labeling and biodistribution of anti-TAC disulfide-stabilized Fv
      fragment.
AB  - We used a preformed 99mTc chelate approach to label a genetically engineered
      disulfide-bonded Fv fragment of anti-Tac monoclonal antibody (dsFv). The
      biodistribution of this 99mTc-labeled dsFv was evaluated in athymic mice with IL
      2 alpha-receptor-positive ATAC4 tumor xenografts. METHODS: Benzoylmercaptoacetyl
      triglycine (BzMAG3) was first labeled with 99mTc, and the carboxy group of 99mTc
      MAG3 was then activated to the corresponding tetrafluorophenyl ester. This
      activated ester was purified with a Sep-Pak C18 column and conjugated to dsFv.
      The resulting 99mTc-MAG3-dsFv was purified with PD-10 size-exclusion
      chromatography. The immunoreactivity of 99mTc-MAG3-dsFv was 76% +/- 9%. When
      incubated in serum at 37 degrees C for 24 hr, there was no appreciable
      dissociation of 99mTc. The mice were co-injected with 125I-dsFv labeled by the
      Iodo-Gen method as a control. The mice were killed at 15 to 720 min for analysis
      of biodistribution and radiocatabolites. RESULTS: The tumor uptake of 99mTc-MAG3
      dsFv was similar to that of 125I-dsFv. The tumor uptake of 99mTc-MAG3-dsFv was
      rapid with tumor-to-blood or tumor-to-organ ratio higher than 1 for all organs
      except the kidneys. The peak tumor value of 5.1% injected dose per gram was
      obtained at 45 min, and the tumor-to-organ ratios increased steadily over time; a
      ratio of 15, 11, 7, 95 and 0.10 resulted at 6 hr for blood, liver, stomach,
      muscle and kidney. The radioactivity was primarily excreted through kidneys.
      CONCLUSION: The rapid achievement of high tumor-to-blood and -tissue ratios makes
      99mTc-MAG3-dsFv a promising agent for scintigraphic detection of various
      hematological malignancies that express IL-2 alpha receptors.

PMID- 9025759
TI  - Implementation and evaluation of patient-specific three-dimensional internal
      dosimetry.
AB  - Current methods for calculating the absorbed dose in a target region from a
      source region rely on a standard "reference man" geometry and assume an uniform
      distribution of radiolabel. While this approach is acceptable at the low levels
      of radioisotope administered for most diagnostic purposes, the generality of the
      calculations is not adequate for doses at the higher levels required for therapy
      and is not easily extendible to tumor dosimetry. METHODS: We have developed an
      integrated system which utilizes patient anatomy and radionuclide distribution in
      the calculation of absorbed dose rate or total dose to any user-defined target
      region. Images of radionuclide distribution (PET/SPECT) are registered to
      anatomic images (CT/ MRI) and then entered into a three-dimensional internal
      dosimetry software system (3D-ID) where regions of interest are defined. Dose
      calculations are performed by the mathematical convolution between a user
      specified, dose-point kernel with the activity in the source volume over the
      target volume. The resulting dose rate distribution may be scaled by cumulated
      activity to yield absorbed dose. In addition to calculating the mean dose, dose
      volume histograms may be generated which plot absorbed dose with respect to
      percent of volume. The method was evaluated using selected standard man phantom
      organs. RESULTS: Dose estimates for two patient studies are included to
      illustrate differences between patient-specific and MIRD-based calculations. The
      package provides an alternative approach to image display and three-dimensional
      internal dose calculations. CONCLUSION: The dose-volume histogram representation
      of absorbed dose to a target volume provides valuable information in assessing
      tumor control probability and normal tissue toxicity.

PMID- 9025760
TI  - Patient-specific dosimetry using quantitative SPECT imaging and three-dimensional
      discrete Fourier transform convolution.
AB  - The objective of this study was to develop a three-dimensional discrete Fourier
      transform (3D-DFT) convolution method to perform the dosimetry for 131I-labeled
      antibodies in soft tissues. METHODS: Mathematical and physical phantoms were used
      to compare 3D-DFT with Monte Carlo transport (MCT) calculations based on the EGS4
      code. The mathematical and physical phantoms consisted of a sphere and a
      cylinder, respectively, containing uniform and non-uniform activity
      distributions. Quantitative SPECT reconstruction was carried out using the
      circular harmonic transform (CHT) algorithm. RESULTS: The radial dose profile
      obtained from MCT calculations and the 3D-DFT convolution method for the
      mathematical phantom were in close agreement. The root mean square error (RMSE)
      for the two methods was < 0.1%, with a maximum difference < 21%. Results obtained
      for the physical phantom gave a RMSE < 0.1% and a maximum difference of < 13%;
      isodose contours were in good agreement. SPECT data for two patients who had
      undergone 131I radioimmunotherapy (RIT) were used to compare absorbed-dose rates
      and isodose rate contours with the two methods of calculation. This yielded a
      RMSE < 0.02% and a maximum difference of < 13%. CONCLUSION: Our results showed
      that the 3D-DFT convolution method compared well with MCT calculations. The 3D
      DFT approach is computationally much more efficient and, hence, the method of
      choice. This method is patient-specific and applicable to the dosimetry of soft
      tissue tumors and normal organs. It can be implemented on personal computers.

PMID- 9025761
TI  - Quantitative blood flow measurement of skeletal muscle using oxygen-15-water and
      PET.
AB  - The aim of the present study was to evaluate quantitation of muscle blood flow
      using [15O]H2O and PET. METHODS: The autoradiographic (ARG) and the steady-state
      methods using PET were used to measure femoral muscle blood flow. A simulation
      study was performed to examine the errors due to contamination of radioactivity
      in the blood content in muscle tissue, statistical noise and delay and the
      dispersion of the input curve in the ARG method. Five separate paired muscle
      blood flow examinations were carried out for comparison of the ARG and the steady
      state techniques, including measurement of muscle blood volume in each subject.
      To obtain the normal range for resting muscle blood flow, additional measurements
      with the ARG method were performed in 16 normal subjects. RESULTS: When the
      integration time in ARG was increased to 200-300 sec, the errors due to arterial
      blood volume, statistical noise, delay and dispersion of the input curve were
      significantly reduced. Muscle blood flow values in the ARG (200 sec) and the
      steady-state studies were in good agreement, and each provided an estimated
      accuracy of 5%. Resting muscle blood flow averaged 3.12 +/- 1.55 ml/min.100 g
      muscle (range 1.43-6.72 ml/min.100 g muscle, n = 18). CONCLUSION: The ARG and the
      steady-state methods provided consistent blood flow values for skeletal muscle
      when a long tissue integration time (> or = 200 sec) was applied in the ARG
      study. Based on the lower effective radiation dose and the shorter total scan
      duration, the ARG method is favored over the steady-state method in the
      measurement of muscle blood flow.

PMID- 9025763
TI  - A "hybrid" method for measuring myocardial wall thickening from gated PET/SPECT
      images.
AB  - We introduce a hybrid index, HYB, which combines counts with geometric
      information to measure wall thickening from PET/SPECT gated images. Its accuracy
      is compared with that of a count-based index (MAX) and a geometric index (FWHM).
      METHODS: For each index, the index values versus thickness and the estimated
      thickening values versus true thickening were investigated using theoretical
      analyses, realistic simulated data obtained from clinical gated MR scans, phantom
      measurements and preliminary gated MRI and PET patient studies. Each index was
      studied for different spatial resolutions and noise and background conditions.
      The performance of each index was quantified using a parameter "Q" reflecting
      bias and variability of thickening estimates. RESULTS: HYB varied more linearly
      with thickness than MAX and FWHM, resulting in a better Q value than with MAX and
      FWHM for all noise, background and spatial resolutions. ROC analysis confirmed
      that HYB significantly increases the sensitivity and specificity for detection of
      wall thickening abnormalities (sensitivity = 100%; specificity = 85% for HYB, 95%
      and 50% for MAX and 100% and 0% for FWHM, respectively). CONCLUSION: Use of the
      hybrid index instead of conventional count-based or geometric indices should
      improve the classification of normal/abnormal wall thickening values in gated
      SPECT and PET.

PMID- 9025762
TI  - Clinical fusion of three-dimensional images using Bremsstrahlung SPECT and CT.
AB  - Infusional brachytherapy for treatment of neoplasms, with colloidal 32P has been
      used to treat various tumors in the pancreas, liver, brain, lung, and head and
      neck. In performing such treatments, anatomical verification of the location of
      the administered 32P from the image obtained by Bremsstrahlung SPECT alone is not
      possible due to the lack of internal landmarks, since the radionuclide is
      distributed only in the tumor and does not usually accumulate in the normal
      organs. The purpose of this study was to provide a practical three-dimensional
      approach for image fusion between Bremsstrahlung SPECT and CT. METHODS: The
      tumors in four cancer patients were injected directly with 32P under CT guidance.
      A Bremsstrahlung SPECT study using 99mTc backscatter sources to obtain the body
      contour was then performed. SPECT images were used to generate the skin contours
      using a threshold detection method. A three-dimensional surface was generated
      from these contours using a tiling program and fused with a corresponding CT
      surface generated from a CT scan in the same patient through an iterative surface
      fitting algorithm. The three-dimensional surface of the region of high-activity,
      corresponding to the infused tumor, was then generated using the Bremsstrahlung
      SPECT data by mapping the iso-count surfaces through a computer program. The
      three-dimensional image of the organ then was fused with the registered CT-SPECT
      datasets. RESULTS: The accuracy of fit measured as the mean distance between the
      SPECT and CT surfaces was in the range of 3-4 mm. CONCLUSION: The anatomical co
      registration of Bremsstrahlung SPECT with CT images using the outer surface
      fitting algorithm is a reliable tool. This correlation permits direct anatomic
      confirmation of the region of the 32P activity distribution with the anatomic
      site selected for injection.

PMID- 9025764
TI  - No-carrier-added iodine-131-FIBG: evaluation of an MIBG analog.
AB  - The purpose of this study was to evaluate the properties of 4-fluoro-3
      [131I]iodobenzylguanidine ([131I]FIBG), a potential neuroendocrine tumor and
      myocardial imaging radiopharmaceutical. METHODS: The binding of [131I]FIBG and
      [125I]MIBG was compared in vitro using the SK-N-SH human neuroblastoma cell line.
      The role of the active uptake-1 mechanism was investigated by determining the
      effect on cell binding of desipramine (DMI), ouabain, norepinephrine (NE),
      unlabeled MIBG and FIBG and by incubation at 4 degrees C. Finally, the tissue
      distributions of [131I]FIBG and [125I]MIBG were compared in normal mice. RESULTS:
      The specific binding of [131I]FIBG remained fairly constant (45%-60%) over a 2-3
      log activity range and consistently was 11%-14% higher (p < 0.05) than that of
      [125I]MIBG. The uptake of [131I]FIBG was reduced to 13% of control values by 1.5
      microM DMI, to 31% by 1 mM ouabain, to 8% by lower temperature, to 8% by 50
      microM NE and to 6% and 5% by 10 microM each of unlabeled MIBG and FIBG,
      respectively. The amount of [131I]FIBG retained by SK-N-SH cells was
      significantly higher than that of [125I]MIBG with the maximum difference observed
      at 72 hr. In mice, the uptake of [131I]FIBG was higher than that of [125I]MIBG
      not only in target tissues (heart and adrenals) but also in many other normal
      tissues; conversely, thyroidal uptake of [131I]FIBG was 2-3-fold lower than that
      of [125I]MIBG. The uptake of [131I]FIBG in the heart and adrenals was reduced by
      DMI. CONCLUSION: Iodine-131-FIBG is an analog of MIBG with prolonged binding to
      neuroblastoma cells in vitro and retention in the myocardium in vivo.

PMID- 9025765
TI  - Weighted summation of oxygen-15-water PET data to increase signal-to-noise ratio
      for activation studies.
AB  - Data with the highest possible signal-to-noise (S/N) ratios are desirable when
      performing nonquantitative perturbation studies with PET and 15O-water. To
      achieve this, protocols have been suggested in which the stimulus is switched off
      before the washout phase. An alternative strategy is suggested for cases in which
      the stimulus is not easily discontinued. METHODS: For a given subject, a
      theoretical signal curve is created by simulating tissue time-activity curves for
      baseline and activated states and their subtraction. The curve is created from a
      typical arterial curve, and values for delay and flow are estimated for that
      subject. When summing the activity data before image reconstruction, the values
      from the signal curve are used as weights. Thus, data with high information
      content regarding changes in blood flow are given a large weight, and data with
      less information are given a smaller weight. The method is examined by
      simulations, and the results are validated by application to data from 10
      individuals from an activation study. RESULTS: Simulations show that the S/N
      ratio peaks for a given summation time and then decline for longer times when
      performing a straight summation of data. This time is not constant and varies
      both with the whole brain flow level and the magnitude of the activation. When
      using weighted summation on the other hand, the S/N ratio approaches
      asymptotically its optimal value. The optimal S/N value for weighted summation is
      5%-10% higher than the peak value obtained with straight summation. The results
      are confirmed by the experimental data, indicating a shift in optimal summation
      time from 60-100 sec and an increase by 6% in the S/N ratio for weighted compared
      to straight summation. CONCLUSION: The method presented in this paper offers a
      way to significantly increase the S/N ratio in 15O-water perturbation studies
      without increasing invasiveness or complicating the experimental protocol.

PMID- 9025766
TI  - Reaction volume concept.

PMID- 9025768
TI  - Determination of vinca alkaloids in human plasma by liquid
      chromatography/atmospheric pressure chemical ionization mass spectrometry.
AB  - A sensitive assay was developed for the quantitation of vinblastine,
      desacetylvinblastine and vincristine using liquid chromatography-atmospheric
      pressure chemical ionization mass spectrometry (LC-APCI-MS). Analyses were
      performed on an Ultrasphere C18 microbore column using ammonium acetate as mobile
      phase. The calibration curves were linear across the range of 0.51-4.00 ng/ml
      (0.63-4.93 nM) for vinblastine, 0.74-3.93 ng/ml (0.96-5.11 nM) for
      desacetylvinblastine and 0.30-3.95 ng/ml (0.36-4.79 nM) for vincristine. Vinca
      alkaloid concentrations were measured with an accuracy and precision within 11%.
      This assay could be implemented to determine the plasma concentrations for
      pharmacokinetic studies of vinblastine, desacetylvinblastine and vincristine in
      conjunction with clinical trials.

PMID- 9025767
TI  - A randomized study comparing VMCP and MMPP in the treatment of multiple myeloma.
AB  - PURPOSE: To compare VMCP, a multidrug combination chemotherapy comprising
      vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone
      (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as
      induction, to elucidate the value of alternating combination chemotherapy, and to
      search for an appropriate maintenance therapy in multiple myeloma. METHODS: At 16
      institutions in the Nagoya City area, we carried out a randomized trial of VMCP
      versus MMPP as the initial treatment. Patients who were refractory or resistant
      to the initial therapy were crossed over into the other arm (crossover trial).
      For patients who achieved a partial response (PR) or a minor response (MR) and in
      whom the paraprotein level ceased to decrease, the maintenance therapy was
      randomized either to an MPH/PSL combination (MP) or to alternating combination
      therapy (AT) with VMCP and MMPP. RESULTS: In the 94 evaluable patients of the 111
      enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7%
      (21/47) in the MMPP arm (P = 0.0859). The crossover trial resulted in a PR rate
      of 15.8% (3/19) for the VMCP-->MMPP crossover and 14.3% (2/14) for the MMPP-
      >VMCP crossover. The median survival time was 23.4 months for those initially
      begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a
      tendency for better survival during a follow-up of 2-6 years with MMPP treatment,
      but without statistical significance. The survival time of patients with
      progressive disease was significantly shorter than that of patients with PR, MR
      or no change (NC). However, there was no significant difference in the survival
      rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there
      was no significant difference in survival between MP therapy and AT. Patients who
      reached a plateau phase survived significantly longer than those who did not.
      Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no
      significant difference in the hematologic or gastrointestinal toxicity between
      the two arms. CONCLUSIONS: We conclude that VMCP is less effective for myeloma
      than MMPP as the induction treatment, that alternating noncrossresistant
      chemotherapeutic combinations do not offer an advantage in multiple myeloma, and
      that patients who reach a plateau phase have a significantly longer survival
      time.

PMID- 9025769
TI  - Phase I clinical trial of all-trans-retinoic acid with correlation of its
      pharmacokinetics and pharmacodynamics.
AB  - A phase I trial of all-trans-retinoic acid (ATRA) was conducted to establish the
      maximum tolerable dose (MTD) of ATRA given once daily to patients with solid
      tumors. Cancer patients for whom no standard therapy was available were treated
      with ATRA once daily. Doses were escalated in cohorts of at least three patients.
      The pharmacokinetics of ATRA were assessed on day 1 for all patients and weekly
      for 31 patients who received doses of > or = 110 mg/m2 per day. Patients were
      followed for toxicity and response. Correlations of toxicity frequency and grade
      with pharmacokinetic parameters were sought. In addition, correlation of changes
      in ATRA pharmacokinetics with the concentration of ATRA metabolites in plasma
      were sought. A total of 49 patients received ATRA at doses ranging from 45 to 309
      mg/m2 per day. Hypertriglyceridemia was dose-limiting at 269 mg/m2 per day. Other
      frequent toxicities included mucocutaneous dryness and headache. With chronic
      dosing, plasma ATRA concentrations fell in 59% of patients. Stable, low, or
      variable [ATRA] were seen in 16%, 6%, and 16% of patients respectively. Age,
      gender, smoking, or concurrent medication did not correlate with the
      pharmacokinetic pattern. Severe toxicities tended to occur with initial peak
      [ATRA] of > or = 0.5 microgram/ml (1.7 microM), and the toxicity frequency did
      not change if [ATRA] decreased with continued dosing. No consistent change in 4
      oxo-ATRA or retinoid glucuronide concentrations was observed with decreases in
      plasma [ATRA]. The recommended once-daily ATRA dose is 215 mg/m2, although
      significant interpatient variability is observed in toxicity and plasma retinoid
      concentrations. Although not statistically significant, more frequent and severe
      toxicity tended to occur in patients with higher plasma peak ATRA concentrations.
      Other factors, such as responses at target tissues, may be at least as important
      as the plasma ATRA concentration in predicting toxicity and/or response.

PMID- 9025770
TI  - A phase I study of 5-fluorouracil, leucovorin and levamisole.
AB  - PURPOSE: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced
      by leucovorin and the combination of 5-FU and levamisole has activity in the
      adjuvant treatment of colonic malignancies. The combination of 5-FU with both
      leucovorin and levamisole may provide additional benefit in the treatment of
      colon cancer. METHODS: A phase I study to assess qualitative and quantitative
      toxicities of this three-drug combination and to determine a dose for further
      phase II testing was undertaken. The role of levamisole as an immunomodulator was
      also assessed. RESULTS: A group of 38 patients with incurable metastatic
      malignancies received 119 cycles of treatment at eight dose levels. 5-FU (375
      mg/m2 per day) and leucovorin (200 mg/m2 per day) were administered intravenously
      (days 1-5). Levamisole was administered orally (days 1-3 and 15-17) at doses from
      30 to 470 mg/m2 per day. Patients received both 5FU/leucovorin and 5
      FU/leucovorin/levamisole in random order for their initial two cycles. All
      subsequent treatments were with the three-drug combination. Toxicities included
      nausea, vomiting, stomatitis, thrombocytopenia and granulocytopenia. Diarrhea was
      the dose-limiting toxicity at 470 mg/m2 per day levamisole. The addition of
      levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical
      responses were seen with this regimen. The addition of levamisole resulted in
      more immunomodulation than 5-FU and leucovorin alone as evidenced by release of
      neopterin from monocytes. CONCLUSION: With this schedule and dose of 5-FU and
      leucovorin, the maximum tolerated dose of levamisole was 354 mg/m2. However,
      given the lack of response and the absence of dose-dependent immunomodulation,
      this may not be the appropriate dose for further phase 11 studies.

PMID- 9025771
TI  - Intraarterial O6-benzylguanine enables the specific therapy of nitrosourea
      resistant intracranial human glioma xenografts in athymic rats with 1,3-bis(2
      chloroethyl)-1-nitrosourea.
AB  - The prognosis for patients with malignant gliomas continues to be dismal. The
      high degree of resistance of gliomas to nitrosourea-based chemotherapy is one
      major factor in poor treatment outcome. The identification of O6-alkylguanine-DNA
      alkyltransferase (AGAT) as a major determinant of nitrosourea resistance has
      resulted in the development of several agents to inactivate this repair protein
      and counteract tumor cell resistance. However, a major problem in preclinical
      trials has been the marked nitrosourea dose limitations imposed by the prior
      administration of AGAT-depleting agents. We investigated the AGAT depletion and
      selective enhancement of BCNU activity of intraarterial (i.a.) O6-benzylguanine
      (O6BG) in the human malignant glioma xenograft D-456 MG growing intracranially
      (i.e.) in athymic rats. Whereas i.a. O6BG at 2.5 mg/kg produced 100% inhibition
      of D-456 MG AGAT i.e. activity 8 h after administration, intraperitoneal (i.p.)
      O6BG at this dose produced only 40% inhibition, requiring dose escalation to 10
      mg/kg to produce 100% AGAT depletion. Prior administration of i.p. O6BG (10
      mg/kg) and i.a. O6BG (2.5 mg/kg) limited maximum tolerated intravenous (i.v.)
      BCNU doses (37.5 mg/kg when given alone) to 6.25 and 25 mg/kg, respectively.
      Higher doses of BCNU alone or in combination with O6BG produced histopathologic
      evidence of cerebral and hepatic toxicity. Therapy experiments revealed a
      significantly improved median survival for rats treated with O6BG i.a. (2.5
      mg/kg) plus BCNU i.v. (25 mg/kg, days 61 and 59 in duplicate experiments)
      compared with saline (day 21. P = 0.001). O6BG i.a. or i.p. (days 22 and 23, P =
      0.001), BCNU i.v. (37.5 mg/kg, day 29, P = 0.001), and O6BG i.p. (10 mg/kg), plus
      BCNU i.v. (6.25 mg/kg, day 37, P < 0.001). Therefore, O6BG i.a., by virtue of
      rapid AGAT depletion and selective uptake into i.c. tumors, offers significant
      potential for regional chemomodulation of AGAT-mediated nitrosourea resistance in
      malignant human gliomas with concomitant reduction of systemic toxicity.

PMID- 9025772
TI  - A sequential Bayesian algorithm for dose individualisation of carboplatin.
AB  - Carboplatin is associated with significantly less nephrotoxicity and
      neurotoxicity than is cisplatin. The dose-limiting toxicity of carboplatin is
      myelotoxicity. A number of dosing methods have been described that allow a value
      for the area under the concentration-time curve to be targeted on the basis of
      the patient's renal function. Recently a formalised analysis of the
      pharmacodynamic response to carboplatin revealed a therapeutic window in which
      the response rate was maximal and toxicity, tolerable. Optimal therapy would
      result from targeting this window in the individual patient. The aim of this
      study was to develop a Bayesian dose-individualisation method for carboplatin.
      The method involved (1) development of a high-performance liquid chromatography
      (HPLC) method to measure serum concentrations of carboplatin; (2) a
      pharmacokinetic study in 12 women receiving carboplatin for ovarian cancer to
      estimate the population pharmacokinetic values for this group of patients; (3)
      development of population models to describe the concentration-time course of
      carboplatin in serum along with associated errors; and (4) development of an
      algorithm that uses a sequential Bayesian design, which enables estimation of
      future doses of carboplatin on the basis of feedback from serum concentrations.
      The results of each of the stages were (1) the coefficient of variation of the
      assay was 6.3% within day and 8.4% between days (r2 = 0.9993), and the limit of
      detection was 0.25 mg/l; (2) Patients' ages ranged from 49 to 68 years, their
      weights varied from 46 to 85 kg, and their glomerular filtration rate ranged from
      3.2 to 7.4 l/h. A geometric mean clearance (Cl) of 6.8 L/h and a steady-state
      volume of distribution (Vss) of 221 were estimated, which are similar to
      previously published data; (3) and a two-compartment model best described the
      data. Two error models were developed, the first describing the error associated
      with the assay and the second, the error of the two-compartment model, i.e. error
      due to individual variation in pharmacokinetics and error due to model mis
      specification. Finally, (4) the development of a sequential Bayesian dose
      individualisation method for carboplatin is described. To our knowledge, this is
      the first sequential design that has been used for dose individualisation of
      chemotherapy. The program is specific for carboplatin and operates independently
      of commercially available Bayesian software. Doses predicted by this program are
      being tested prospectively against conventional dosing methods.

PMID- 9025773
TI  - A phase I study of irinotecan and infusional cisplatin for advanced non-small
      cell lung cancer.
AB  - A phase I study was performed to establish the optimum dose for combination
      therapy with infusional cisplatin and irinotecan (CPT-11) in non-small-cell lung
      cancer (NSCLC). The subjects were 20 patients with a performance score of 0-2
      with untreated advanced NSCLC. Cisplatin was administered by 5-day continuous
      intravenous infusion at 20-25 mg/m2 per day. CPT-11 was administered by bolus
      infusion at a starting dose of 20 mg/m2 on days 1 and 8 or 60 mg/m2 per day on
      day 1 alone, followed by serial increments of 20 mg/m2. Since grade 4
      granulocytopenia was observed in two of the five patients receiving 20 mg/m2 per
      day cisplatin (days 1-5) and 100 mg/m2 CPT-11 (day 1), and since one of them
      developed severe pneumonia and sepsis associated with the granulocytopenia, the
      regimen was considered to be intolerable. In the same patient, grade 4
      thrombocytopenia and grade 3 diarrhea were observed. Therefore, the optimum dose
      appeared to be 20 mg/m2 per day (days 1-5) for cisplatin and 80 mg/m2 (day 1) for
      CPT-11. The side effects were grade 2 diarrhea in one of three patients, and
      grade 2 vomiting in three patients, but grade > or = 2 hemotoxicity was not
      observed. This combined regimen resulted in a partial response in 9 out of 19
      assessable patients. The dose-limiting factor in this combination therapy was
      granulocytopenia, and a high efficacy rate was obtained.

PMID- 9025774
TI  - Augmentation of vincristine cytotoxicity by megestrol acetate.
AB  - PURPOSE: To determine the effect of a semisynthetic progesterone, megestrol
      acetate (MA), on the cytotoxicity of various chemotherapeutic agents including
      vincristine, doxorubicin, actinomycin-D, taxol, vinblastine and colchicine in
      cell lines with or without P-gp expression. METHODS: Three cell lines with high P
      gp expression (two colon cancer and one leukemia), and a control cell line with
      no P-gp expression were exposed to chemotherapeutic agents in the presence or
      absence of MA and drug sensitivity was determined using the MTT colorimetric
      assay. P-gp-170 expression was detected by flow cytometry using JSB-1 monoclonal
      antibody and the functionality of MDR expression was tested by rhodamine-123
      uptake studies. In vitro drug accumulation studies were performed using [3H]
      vincristine. The results were subjected to paired t-test analysis and 95%
      confidence intervals were determined in cytotoxicity tests. RESULTS: MA augmented
      the cytotoxicity of vincristine, but not doxorubicin, actinomycin-D, taxol,
      vinblastine or colchicine in the three P-gp-expressing cell lines, whereas
      verapamil augmented the cytotoxicity of doxorubicin and vincristine. MA did not
      augment the cytotoxicity of vincristine in the P-gp-negative HUT-102 cell line.
      CONCLUSION: MA augmented vincristine cytotoxicity in P-gp-expressing cell lines.
      However, this phenomenon did not occur with the other classic MDR drugs.
      Therefore, the augmentation of vincristine cytotoxicity by MA can be explained
      either by involvement of a different mechanism that coexists with the mdr-1
      phenotype or by the presence of a different affinity or binding site on the P-gp
      molecule for MA compared to that for the other classic MDR drugs and verapamil.

PMID- 9025775
TI  - Cisplatin-induced inhibition of the calcium-calmodulin complex, neuronal nitric
      oxide synthase activation and their role in stomach distention.
AB  - Cisplatin (8 mg/kg; i.p.) treatment of Wistar rats produced no change in nitric
      oxide synthase (NOS) localization or its intensity for up to 5 days. However,
      immunohistochemically the levels of L-citrulline and the Ca(2+)-calmodulin
      complex were decreased after only 3 days. An in vitro experiment using an analog
      of calmodulin. Mero-Calmodulin-1, showed that cis-diammine-diaquacisplatinum(II),
      a hydrolyzed form of cisplatin, inhibited the calmodulin conformational shift
      from occurring through a direct interaction with the calmodulin molecule. The
      results indicate that distention of the stomach was due to inhibition of neuronal
      NOS activation by a direct interaction between cisplatin and the calcium binding
      sites of the calmodulin molecule.

PMID- 9025776
TI  - A phase II trial of all-trans-retinoic acid in hormone-refractory prostate
      cancer: a clinical trial with detailed pharmacokinetic analysis.
AB  - Retinoids have been shown to have substantial anticancer activity in a number of
      preclinical and clinical situations. There are considerable epidemiologic, in
      vitro and in vivo data which indicate that retinoids may have a role in the
      prevention and therapy of human prostate cancer. Based on anecdotal evidence of
      response in one patient with hormone-refractory prostate cancer (HRPC), we
      conducted a phase II trial in HRPC during which we also examined changes in
      pharmacokinetics of all-trans-retinoic acid (ATRA) which occurred during therapy.
      Enrolled in the study were 17 patients with HRPC who received 50 mg/m2 ATRA three
      times daily orally on days 1-14, repeated every 22 days. The pharmacokinetics of
      ATRA were assessed with the first dose on day 1, again on day 14 and after a 7
      day interruption in ATRA therapy on day 22. Patients were evaluable for response
      if they completed two 14-day courses of ATRA; among 13 such patients no responses
      were seen. Four patients were considered unevaluable for response owing to rapid
      disease progression in three and intercurrent illness in one. Apparent clearance
      of ATRA changed substantially during therapy: day 1 3779 +/- 4215 ml/min, day 14
      7179 +/- 3197 ml/min, day 22 3213 +/- 2357 ml/min. Area under the curve was
      proportionately diminished on day 14 compared with day 1 and had returned to
      baseline by day 22. We conclude that ATRA is not active in HRPC. Failure of this
      agent in HRPC may be related to failure of drug delivery associated with enhanced
      mechanisms of ATRA clearance which occur within a few days of beginning ATRA
      treatment.

PMID- 9025777
TI  - Gastric mucosal blood flow and gastric secretion following intravenous
      administration of 5-fluorouracil in anesthetized rats.
AB  - Acute gastric mucosal lesions are often observed after the intravenous
      administration of high doses of anticancer drugs. To investigate the acute toxic
      effects of such anticancer therapy on the gastric mucosa, 5-fluorouracil (5-FU)
      was administered intravenously to anesthetized rats. Gastric mucosal blood flow
      (GMBF) was measured continuously using laser Doppler velocimetry. Acid secretion
      was measured using a perfusion method for 1 h after the administration of 5-FU.
      No significant change was observed with a low dose of 5-FU (50 mg/kg), but a high
      doses of 5-FU (100 or 200 mg/kg) caused a significant decrease in GMBF in a dose
      dependent manner. The selective antagonist of the muscarinic acetylcholine
      receptor, pirenzepine, prevented the decrease in GMBF with high doses of 5-FU.
      Acid secretion decreased after the administration of 5-FU, but not significantly.
      This study indicates that a decrease in GMBF may be an important factor in
      gastric mucosal injury induced by chemotherapy. Pirenzepine may prevent the
      gastric mucosal lesions which are induced by the administration of 5-FU.

PMID- 9025778
TI  - Modification of the antitumor activity of chemotherapeutic drugs by the hypoxic
      cytotoxic agent tirapazamine.
AB  - PURPOSE: Preclinical studies were performed to examine the interaction of the
      hypoxic cell toxin tirapazamine (TPZ), a benzotriazine di-N-oxide, with several
      chemotherapeutic agents, including carboplatin, cyclophosphamide, doxorubicin,
      etoposide, 5-fluorouracil (5-FU), taxol, and navelbine. METHODS: The modification
      by TPZ of the antitumor drug activity and the effect of schedule were determined
      with an in vivo/in vitro clonogenic assay using well-established RIF-1 murine
      tumors transplanted into C3H mice. RESULTS: Additive, or greater than additive,
      tumor cell killing was observed when TPZ was combined with carboplatin,
      cyclophosphamide, doxorubicin, etoposide, 5-FU and taxol. With the exception of 5
      FU there were only small, or no, enhancements of the systemic toxicities of the
      drugs by TPZ. The greatest enhancement of antitumor activity was with
      carboplatin, with the maximum effectiveness when TPZ was given 2-3 h before the
      carboplatin. The activity of cyclophosphamide, doxorubicin, etoposide and taxol
      were most enhanced when TPZ was given 24 h before the drug. Additional
      investigations with three-drug combination treatments using cisplatin and TPZ
      with either etoposide or navelbine indicated a substantial therapeutic gain from
      the addition of TPZ. CONCLUSIONS: The data for each of the drugs tested in
      combination with TPZ, with the exception of 5-FU, indicate that potential
      clinical benefit may be obtained from therapies combining TPZ with conventional
      chemotherapy.

PMID- 9025779
TI  - Complementation of temperature-sensitive topoisomerase II mutations in
      Saccharomyces cerevisiae by a human TOP2 beta construct allows the study of
      topoisomerase II beta inhibitors in yeast.
AB  - We show herein that human DNA topoisomerase II beta is functional in yeast. It
      can complement a yeast temperature-sensitive mutation in topoisomerase II. The
      effect on human topoisomerase II beta of a number of topoisomerase II inhibitors
      was analysed in a yeast in vivo system and compared with that of human
      topoisomerase II alpha and wild-type yeast topoisomerase II. A drug permeable
      yeast strain (JN394 top2-4) was used to analyse the in vivo effects of known anti
      topoisomerase II agents on human topoisomerase II beta transformants. A parallel
      analysis on human topoisomerase II alpha transformants provides the first in vivo
      analysis of the responses of yeast bearing the individual isoforms to these
      drugs. The strain was analysed at 35 degrees C, a non-permissive temperature at
      which only plasmid-borne topoisomerase II is active. A shuttle vector with either
      human topoisomerase II beta, human topoisomerase II alpha or yeast topoisomerase
      II under the control of a GAL1 promoter was used. The key findings were that
      amsacrine produced comparable levels of cell killing with both alpha and beta,
      whilst etoposide, doxorubicin and mitoxantrone produced higher degrees of cell
      killing with alpha than with beta or yeast topoisomerase II. Merbarone had the
      greatest effect on the yeast strain bearing plasmid-borne yeast topoisomerase II.
      Suramin, quercetin and genistein showed little cell killing in this system. This
      yeast in vivo system provides a powerful way to analyse the effects of anti
      topoisomerase II agents on transformants bearing the individual human isoforms.
      This system also provides a means of analysing putative drug-resistance mutations
      in human topoisomerase II beta or to select for drug-resistance mutations in
      human topoisomerase II beta.

PMID- 9025780
TI  - High-dose carmustine for high-grade gliomas in childhood.
AB  - Carmustine (BCNU) has proved to be of value against a variety of primary brain
      tumors. This agent exhibits a steep dose-response curve in in vitro and animal
      tumor models and has been proposed for use in high-dose chemotherapy as a single
      agent or in combination. We conducted a phase II study to assess high-dose BCNU
      in children with high-grade gliomas. A total of 13 children with high-grade
      gliomas were treated in a phase II study using high-dose BCNU (800 mg/m2)
      followed by autologous bone marrow transplantation. Eight patients were newly
      diagnosed, and five were treated at the time of tumor recurrence. Seven patients
      had diffuse intrinsic brain-stem gliomas. The response was assessed at 1 month
      after treatment. Only one objective effect was observed. Five patients had stable
      disease and seven progressed. The immediate toxicity was mild; however, one
      patient developed fatal respiratory distress at 50 days after treatment with high
      dose BCNU. Dose escalation of BCNU does not seem beneficial in children with high
      grade gliomas.

PMID- 9025781
TI  - Tamoxifen-induced estrogen receptor up-regulation in mammary tumor cells is not
      related to growth inhibition.
AB  - Treatment of estrogen receptor (ER)-positive mammary tumors with tamoxifen
      produces a dramatic accumulation of ER in the cell nucleus. We investigated
      whether this phenomenon might be related to the antitumor activity of the drug.
      Five tamoxifen derivatives for which an influence on MCF-7 cell growth had
      previously been established were tested for that purpose; two of them inhibited
      growth, one was growth-stimulatory, and the remaining two were without
      significant effect. At 1 microM all compounds up-regulated ER in the cell nucleus
      after 3 days of culture, suggesting that the ER accumulation does not predict the
      response to tamoxifen treatment. An analysis of a tamoxifen-resistant clone (RT x
      6 cells) under similar experimental conditions led to the same conclusion: the ER
      level significantly increased in the presence of tamoxifen and its 4-hydroxy
      metabolite.

PMID- 9025782
TI  - Extensive lymph-node dissection in gastric cancer: is it of therapeutic value?

PMID- 9025783
TI  - Adjuvant therapy for stage I testicular cancer.

PMID- 9025784
TI  - Use of bisphosphonates in cancer patients.

PMID- 9025785
TI  - Effects of bone metastases on bone metabolism: implications for diagnosis,
      imaging and assessment of response to cancer treatment.

PMID- 9025786
TI  - Enhancement of micronuclei frequency by vindesine in mouse bone marrow.
AB  - Treatment of mice with various doses (0, 0.25, 0.5, 1.0 and 2.0 mg/kg b.wt.) of
      vindesine resulted in a dose-dependent increase in the frequency of
      micronucleated polychromatic erythrocytes (MPCE) and micronucleated
      normochromatic erythrocytes. Conversely, the polychromatic erythrocyte and
      normochromatic erythrocyte (P/N ratio) ratio declined with increasing dose of
      vindesine. The dose effect relationship for MPCE, MNCE and P/N ratio was linear
      quadratic.

PMID- 9025787
TI  - Antimutagenicity of Tochu tea (an aqueous extract of Eucommia ulmoides leaves):
      1. The clastogen-suppressing effects of Tochu tea in CHO cells and mice.
AB  - The suppressing effect of crude extracts of Tochu tea, an aqueous extract of
      Eucommia ulmoides leaves and a popular beverage in Japan, on the induction of
      chromosome aberrations in CHO cells and mice was studied. When CHO cells were
      treated with Tochu tea crude extract after MMC treatment, the frequency of
      chromosome aberrations was reduced. Out of 17 Tochu tea components, 5 irridoids
      (geniposidic acid, geniposide, asperulosidic acid, deacetyl asperulosidic acid,
      and asperuloside) and 3 phenols (pyrogallol, protocatechuic acid, and p-trans
      coumaric acid) were found to have anticlastogenic activity. Since the
      anticlastogenic irridoids had an alpha-unsaturated carbonyl group, this structure
      was considered to play an important role in the anticlastogenicity. The
      anticlastogenic effect of Tochu tea extracts was examined in mice using a
      micronucleus assay. When mice received 1.0 ml 4% Tochu tea extract by oral gavage
      6 h before intraperitoneal injection of MMC, a decrease in the frequency of
      micronuclei was observed. This decrease was not due to a delay in the maturation
      of micronucleated reticulocytes.

PMID- 9025788
TI  - Rapid identification of RT-PCR clones containing translation-terminating
      mutations.
AB  - The technique of in vitro transcription/translation (IVTT) has become an
      important method of detecting mutations that result in a prematurely terminated
      protein. Subsequent characterization of the mutations by cloning and sequencing
      the RT-PCR products, however, is often difficult and time consuming. This is due
      in large part to the altered metabolism to which transcripts containing
      translation terminating mutations are subject. Recent data has shown that mRNAs
      with nonsense or frame shift mutations are often selectively degraded, so that
      mutation bearing transcripts are significantly less abundant that wild-type
      transcripts and, after cloning, mutant clones are correspondingly scarce. We have
      developed a reliable method of identifying the cDNA clones containing translation
      terminating mutations by a 'second round' of IVTT. Clones are subjected to PCR
      and IVTT using similar conditions as in the initial IVTT reaction and are
      identified unequivocally as either wild-type or mutant prior to sequencing.
      Wasteful 'blind' sequencing is thus avoided as well as possible misidentification
      of taq polymerase errors as the mutation of interest.

PMID- 9025789
TI  - Human lymphocyte micronucleus genotoxicity test with mixtures of phytochemicals
      in environmental concentrations.
AB  - This study was carried out to assess the genotoxicity of mixtures of pesticides
      using the micronucleus test with human lymphocytes in culture. Benomyl, azinphos
      methyl, diazinon, dimethoate, pirimiphos-methyl pesticides were tested at doses
      estimated from their daily intake (EDI). Benomyl is a carbamate fungicide, the
      other compounds are organophosphorous insecticides. The compounds were tested
      both separately and in combination. The results showed a weak genotoxicity for
      three of the four organophosphorous insecticides and for benomyl. The various
      mixtures did not give additive effects.

PMID- 9025790
TI  - Detection of chemically induced DNA lesions in multiple mouse organs (liver,
      lung, spleen, kidney, and bone marrow) using the alkaline single cell gel
      electrophoresis (Comet) assay.
AB  - The effect of 2 model chemical mutagens on DNA was evaluated with the alkaline
      single cell gel electrophoresis (SCG) (Comet) assay in 5 mouse organs--liver,
      lung, kidney, spleen and bone marrow. Mice were sacrificed 3 and 24 h after the
      administration of the direct mutagen ethyl nitrosourea (ENU) or the liver
      targeting promutagen p-dimethylaminoazobenzene (DAB). Each organ was minced,
      suspended at a concentration of 1 g/ml in chilled homogenizing buffer (pH 7.5)
      containing 0.075 M NaCl and 0.024 M Na2EDTA, homogenized gently using a Potter
      type homogenizer at 500-800 rpm set in ice, and then centrifuged nuclei were used
      for the alkaline SCG assay. ENU induced DNA damage in cells all of the organs
      studied DAB, on the other hand, produced a positive response in the liver only.
      We suggest that it may be possible to use the alkaline SCG assay using a
      homogenization technique to detect the genotoxicity of chemicals in vivo in their
      target organs.

PMID- 9025791
TI  - Evaluation of potential genotoxicity of pulsed electric and electromagnetic
      fields used for bone growth stimulation.
AB  - Medical devices emitting pulsed electric and electromagnetic fields have been
      found to be effective for a number of clinical applications including stimulation
      of bone and tissue growth. To determine whether pulsed fields of the type used in
      these clinical applications present a mutagenic hazard, electric and
      electromagnetic fields at two exposure levels were tested in the Ames test, CHO
      cell chromosomal aberration assay, BALB/3T3 cell transformation assay and
      unscheduled DNA synthesis assay in primary rat hepatocytes. For both field types,
      initial and independent repeat studies were performed for each assay at both
      clinical and supra clinical doses. In all assays, the results show a lack of
      cytotoxic, transforming and mutagenic activity. The data suggest that pulsed
      electric and electromagnetic fields of the type and dose levels used in bone
      growth stimulation lack mutagenic and transforming activity.

PMID- 9025792
TI  - A comparison of the soft agar and microtitre methodologies for the L5178Y tk +/-
      mouse lymphoma assay.
AB  - The L5178Y tk +/- mouse lymphoma assay (MLA) has been validated as a sensitive
      and specific test system for the detection of mutagens/clastogens. There are
      currently two methodologies for performing the MLA: the original soft agar
      procedure and the newer microtitre procedure. While both procedures are
      considered acceptable, a limited amount of comparative information exists for the
      two methods. In this report the two methods were compared with regard to: (1)
      spontaneous and induced mutant frequencies; (2) cloning efficiencies; and (3)
      colony size distributions for mutants. In addition, small and large mutant
      colonies from microtitre wells were rechallenged for trifluorothymidine (TFT)
      resistance. In a majority of the cases, cloning efficiency values were higher for
      the microtitre as were the spontaneous and induced mutation frequency (MF)
      values. Nevertheless, when responses were compared according to mutation index
      (fold increase over background MF) the results from the two systems were often
      similar. More spontaneous small colonies were observed in the microtitre assay.
      While colony size distribution for induced mutant colonies was compound specific,
      generally, more small colonies were counted in microtitre. All mutant clones that
      were rechallenged with TFT demonstrated resistance. Aside from the differences
      mentioned above, both the microtitre and the soft agar procedures appear equally
      capable of identifying mutagenic agents.

PMID- 9025793
TI  - Metabolic activation of 2- and 3-nitrodibenzopyranone isomers and related
      compounds by rat liver S9 and the effect of S9 on the mutational specificity of
      nitrodibenzopyranones.
AB  - The effect of rat liver S9 on the mutagenicity of 10 nitrated polycyclic aromatic
      hydrocarbons (nitro-PAHs) was evaluated with Salmonella typhimurium TA98NR using
      S9 from phenobarbital-, 3-methylcholanthrene (MC)-, beta-naphthoflavone- and
      polychlorobiphenyl-treated and untreated rats. 2-Nitrofluorene (2-NFI), 2
      nitrofluoren-9-one (2-NFlone), 2-nitrocarbazole (2-NCz), 3-NCz, 2
      nitrodibenzothiophene (2-NDBT), 2-nitro-6H-dibenzo[b,d]pyran-6-one (2-NDBP) and 3
      NDBP were metabolically activated by one or more of the S9 fractions, and the
      highest enhancement of the mutagenic potency of nitro-PAHs was observed with 3-MC
      induced S9. Only in the case of 3-NFlone was the mutagenicity in strain TA98NR
      decreased by the addition of S9, regardless of S9 induction. 2-NDBP was most
      efficiently activated among nitro-PAHs tested by all S9 fractions used. The
      cytosolic fraction of S9 accounted for more of the activation of 2-NDBP than the
      microsomal fraction. NADH and NADPH were the most effective electron donors on
      the activation of 2-NDBP by S9, 2-NDBP was also metabolically activated by NADH
      plus commercial preparations of xanthine oxidase. These activations of 2-NDBP
      were inhibited by allopurinol, indicating that cytosolic xanthine oxidase in rat
      liver S9 participates in the activation of 2-NDBP. The potency of 2- and 3-NDBP
      isomers as base-substitution mutagens was also enhanced by S9. In the presence of
      S9, both compounds showed the highest mutagenicity in strain TA7005 (C.G-->A.T)
      followed by strains TA7004 (G.C-->A.T), TA7006 (C.G-->G.C) and TA7002 (T.A-
      >A.T), and this mutation specificity was similar to that without S9, indicating
      that the mechanism of mutagenesis caused by NDBP isomers with S9 is similar to
      that without S9.

PMID- 9025794
TI  - Inhibitory effect of chlorophyllin on the frequency of sister chromatid exchanges
      produced by benzo[a]pyrene in vivo.
AB  - The study was designed to determine the antigenotoxic potential of chlorophyllin
      (Chl), against the frequency of sister-chromatid exchanges (SCE) produced by
      benzo[a]pyrene (B[a]P) in vivo. We used the mouse bone marrow test system to
      measure the effect of a single injection of the compounds: 40 mg/kg of B[a]P, and
      1 h later, 1.0, 2.0, 4.0 and 8.0 mg/kg of Chl. As controls we included both
      chemicals using the dosages mentioned above as well as mineral oil (0.25 mg/kg).
      The results indicated the following: (1) Chl per se was not genotoxic, showing
      SCE values in the range of the control level; (2) B[a]P increased the rate of
      SCEs three times in relation to the basal level; (3) the SCE level produced with
      B[a]P was diminished by all 4 doses of Chl, but better results were obtained with
      2-4 mg/kg, a range which induced Inhibition Indices of 80.9% and 77.5%
      respectively; (4) the Average Generation Time Index was not modified by the
      compounds used in the experiment; and (5) the Mitotic Index also showed no
      significant modification induced by the chemicals, with respect to the control
      value.

PMID- 9025795
TI  - Genotoxicity of malathion in human lymphocytes assessed using the micronucleus
      assay in vitro and in vivo: a study of malathion-exposed workers.
AB  - The aerial application of malathion, a widely used organophosphate insecticide,
      has raised public concerns about potential adverse health effects. We therefore
      studied micronucleus formation in human lymphocytes as a biomarker of
      genotoxicity both in vitro and in vivo. Lymphocytes were cultured either as whole
      blood or after Ficoll isolation and treated with malathion in doses from 5 to 100
      micrograms/ml for 48 h. A significant increase in micronucleated cells (47.5/1000
      versus 16.0/1000 in DMSO control, p < 0.001) was found in isolated lymphocytes at
      high dose levels (75-100 micrograms/ml), concurrent with cytotoxicity and a
      strong inhibition of proliferation (p < 0.001). Many of the treated cells also
      possessed multiple micronuclei. Antikinetochore-antibody staining revealed that
      the majority of malathion-induced micronuclei were kinetochore-negative. A
      significant dose-response was also observed in whole blood cultures, although the
      increase in micronucleated cells was lower than in isolated lymphocyte cultures
      (p = 0.03). When the same technique was applied to lymphocytes of 38
      intermittently malathion-exposed workers involved in the Mediterranean Fruit Fly
      Eradication Program in California, no change in either proliferation or
      micronucleus level was observed compared with an unexposed control group. We
      conclude that malathion has a relatively low potential to cause chromosome damage
      in vitro, and corresponding doses are much higher than ones that even
      professional applicators are likely to be exposed to in vivo. The potential risk
      of chromosome damage for malathion exposure in vivo is therefore relatively low.
      More studies are needed to assess the possibility of interaction of malathion
      with other pesticides through combined exposure.

PMID- 9025796
TI  - Influence of a carbohydrate drink on performance of military personnel in NBC
      protective clothing.
AB  - BACKGROUND: The increased threat of nuclear, biological and chemical (NBC)
      weapons underlines the need of protective clothing and gas masks, but this may
      impair performance. Thus, attention should be focused on the nutritional
      requirements. HYPOTHESIS: Optimal performance is guaranteed if the supply of
      water and energy is adequate. METHODS: Two groups of 20 trained military men
      (mean age 22 yr) received either an isotonic carbohydrate drink or a placebo
      drink (flavored water) for 24 h under simulated NBC conditions (wearing gas masks
      and protective clothing). Various physical and mental tests were performed at
      intervals and blood samples were collected three times. RESULTS: Five men of the
      placebo group had to be withdrawn during the experiment because of exhaustion.
      The decrease in physical performance (about 15%) and mental performance (about
      20%) was most apparent for the group that had only water for consumption.
      CONCLUSIONS: When only water is consumed, physical performance of a group of
      military men decreases during 24 h of simulated NBC conditions. An isotonic
      carbohydrate drink is recommended with respect to maintaining performance under
      NBC conditions. Energy restriction prior to an NBC scenario has a negative
      influence on performance.

PMID- 9025797
TI  - Clothing insulation in a hypobaric environment.
AB  - HYPOTHESIS: Clothing insulation is the result of complex interactions between
      heat transfer mechanisms and clothing material thermal resistances. Hypobaria
      changes the heat transfer processes therefore should have observable effects on
      the clothing insulation. METHODS: The effect of hypobaria on the thermal
      insulative properties of U.S. Army fatigue uniform (BDU) and U.S. Army chemical
      protective overgarment (BDO) were examined Barometric pressure of 429 mmHg,
      comparable to the condition at terrestrial elevation of 4570 m (15,000 ft) above
      sea level was created in a hypobaric chamber. The sea level environment was used
      as a baseline condition. RESULTS: Our data support a diminished convective heat
      transfer and an enhanced evaporative heat transfer at higher altitude. We also
      found that hypobaria had only a small effect on the intrinsic clothing insulation
      values. For the less insulative BDU, hypobaria did not appreciably affect
      clothing insulation values. For the more insulative BDO, a maximum difference of
      0.2 clo (clo = 0.155 m2.K.W-1) was found between hypobaric and normobaric
      environments. CONCLUSION: Heavy clothing insulation forced the heat transfer
      processes at the skin surface to operate almost independently from those at the
      clothing surface. At the skin surface, evaporation was the dominant process,
      while at the outer clothing surface, convection dominated. At higher altitude,
      enhanced evaporative heat transfer resulted in a lower skin temperature, while
      reduced convective heat transfer hampered heat dissipation from clothing surface
      to the ambient environment, hence elevating the clothing temperature. Therefore,
      in hypobaric environment, the skin temperature was found to be lower, but the
      clothing temperature higher than at sea level.

PMID- 9025798
TI  - Cardiovascular deconditioning and venous air embolism in simulated microgravity
      in the rat.
AB  - BACKGROUND: Astronauts conducting extravehicular activities undergo decompression
      to a lower ambient pressure, potentially resulting in gas bubble formation within
      the tissues and venous circulation. Additionally, exposure to microgravity
      produces fluid shifts within the body leading to cardiovascular deconditioning. A
      lower incidence of decompression illness in actual spaceflight compared with that
      in ground-based altitude chamber flights suggests that there is a possible
      interaction between microgravity exposure and decompression illness. HYPOTHESIS:
      The purpose of this study was to evaluate the cardiovascular and pulmonary
      effects of simulated hypobaric decompression stress using a tail suspension (head
      down tilt) model of microgravity to produce the fluid shifts associated with
      weightlessness in conscious, chronically instrumented rats. METHODS: Venous
      bubble formation resulting from altitude decompression illness was simulated by a
      3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h
      of head-down tilt. Heart rate, mean arterial blood pressure, central venous
      pressure, left ventricular wall thickening and cardiac output were continuously
      recorded. Lung studies were performed to evaluate edema formation and compliance
      measurement. Blood and pleural fluid were examined for changes in white cell
      counts and protein concentration. RESULTS: Our data demonstrated that in tail
      suspended rats subjected to venous air infusions, there was a reduction in
      pulmonary edema formation and less of a decrease in cardiac output than occurred
      following venous air infusion alone. Mean arterial blood pressure and myocardial
      wall thickening fractions were unchanged with either tail-suspension or venous
      air infusion. Heart rate decreased in both conditions while systemic vascular
      resistance increased. CONCLUSIONS: These differences may be due in part to a
      change or redistribution of pulmonary blood flow or to a diminished cellular
      response to the microvascular insult of the venous air embolization.

PMID- 9025799
TI  - Effects of sleeping in a chemical protective mask on sleep quality and cognitive
      performance.
AB  - PURPOSE: We wanted to determine whether sleep is disrupted when soldiers sleep in
      a new chemical protective mask, the M40. Sleep quantity and quality, extent of
      protection provided by the mask during sleep, and next day performance were
      assessed. METHOD: After several days of training, 9 male soldiers slept with and
      without the M40 mask on four occasions. RESULTS: Soldiers were able to tolerate
      the mask for most or all of the night. However, sleep, as assessed by wrist-worn
      activity monitors, was significantly disturbed. Minutes (mean +/- SEM) of waking
      significantly increased, from 25 +/- 2.1 to 86 +/- 8.5 per night (p < 0.001), and
      number of awakenings rose from 8 +/- 0.6 to 20 +/- 0.9 (p < 0.0001). Soldiers
      reported that it took longer and was more difficult to fall asleep when wearing
      the mask. Errors on a choice reaction time task increased significantly and
      subjects reported greater fatigue and sleepiness the day after sleeping in the
      mask. Protection provided by the masks varied substantially among subjects and
      declined over the course of the study. Some soldiers were protected throughout
      the night but others were only protected intermittently. CONCLUSION: We conclude
      that sleeping in the chemical protective mask should only be done when necessary,
      given the adverse effects on sleep and daytime function, as well as the
      variability of protection, of the mask.

PMID- 9025800
TI  - Prevalence and significance of spinal disc abnormalities in an asymptomatic
      acceleration subject panel.
AB  - BACKGROUND: A protocol to allow for human centrifuge exposures up to +12 Gz (12
      times gravity) required a screening spinal MRI. MRI-derived spinal disc
      abnormalities were observed in three of the first four asymptomatic volunteer
      subjects. The protocol was interrupted and a second study was initiated to
      determine the possible cause and effect relationship between the disc findings
      and previous +Gz exposure. METHODS: A T1 or T2 weighted sagittal MRI of the
      entire spine was accomplished on each of 22 asymptomatic male acceleration panel
      members, and a similar, age-matched control panel of 19 asymptomatic male
      subjects with no history of previous acceleration exposure. The MRIs from all 41
      subjects were read at 2 diagnostic facilities by 9 radiologists. The evaluating
      radiologists were aware asymptomatic centrifuge subjects were being evaluated but
      were unaware a control group was included. RESULTS: Initial results from any one
      reader revealed spinal disc abnormalities (bulging, degeneration or herniated
      nucleus pulposus-HNP) in 91% of the centrifuge panel and 79% of the control
      group, a non-significant difference. Within-reader and between-reader variability
      was very high. Comparison of 1st vs. 2nd reading of the same data by one
      radiologist demonstrated a 28% agreement and a 72% disagreement on observed
      abnormalities. Comparison of the same MRIs read by two different radiologists
      revealed a 23% agreement and a 77% disagreement, pointing out the ambiguity of
      the data and subjectiveness of the interpretation. Two additional
      neuroradiologists agreed to independently read all 41 MRIs after establishing
      unique reading criteria. There remained a non-significant difference between the
      two subject groups, whereas reader disagreement was still high (56%).
      CONCLUSIONS: No significant difference was found between the two subject groups.
      The power of the test was low because of the small sample size. Our confidence in
      the interpretation is low because of the high degree of between-reader and within
      reader variability.

PMID- 9025802
TI  - The effects of 600 mg of slow release caffeine on mood and alertness.
AB  - BACKGROUND: Caffeine is the most widely used psychostimulant. PURPOSE: This study
      evaluated the pharmacokinetics and effects of mood and alertness of a single oral
      administration of 600 mg of a slow release caffeine (SRC) on a large group of
      healthy subjects. METHOD: In this double-blind, parallel-group study, 120 young
      adult males were randomly assigned to either a caffeine group (CG, n = 100) or a
      placebo group (PC, n = 20). After a normal sleep, each subject took 600 mg of a
      SRC or a placebo. Circulating caffeine was determined by salivary caffeine assays
      after acetylation phenotype categorization. Mood, alertness and nocturnal sleep
      were evaluated by visual analog scales (VAS). RESULTS: This SRC was well
      tolerated probably due to its relative low plasmatic Cmax (10.37 micrograms.ml
      1). Between CG and PG, there were no differences for alertness, contentedness and
      sleep quality of the night after treatment (N2) compared to the previous night
      (N1). VAS scores showed a decrease in calmness in the CG (p < 0.01). Sleep
      latency in N2 was significantly increased with caffeine (p < 0.01). Calmness,
      sleep onset latency, quality of sleep onset and overall rating of N2 compared to
      N1 were correlated with caffeine levels, which were only influenced by tobacco
      consumption. CONCLUSIONS: Although a single oral dose of 600 mg of a SRC is well
      tolerated, further evaluation must be done on alertness and pharmacokinetics with
      fatigued subjects and with females using oral contraceptives.

PMID- 9025801
TI  - Size and myosin heavy chain profiles of rat hindlimb extensor muscle fibers after
      2 weeks at 2G.
AB  - METHOD: The effects of 14 d of continuous centrifugation at approximately 2G on
      the hindlimb extensor musculature of male rats were studied. RESULTS: The mean
      body mass of centrifuged rats was 17% smaller than age-matched controls. In
      centrifuged rats, the mean absolute masses of the soleus and medial gastrocnemius
      (MG) were similar to control, while the mean relative masses (expressed as
      milligram muscle mass/gram of body mass) were larger than control. Based on a
      battery of monoclonal antibodies for specific myosin heavy chains (MHC), the
      soleus of centrifuged rats had a lower percentage (68 vs. 74%) of fibers
      expressing type I MHC only and a higher percentage (15 vs. 10%) that co-expressed
      type I and IIa MHC's. The MHC composition of fibers from the deep portion of the
      MG was unaffected by centrifugation. The MHC compositions based on SDS-PAGE gel
      electrophoresis for each muscle were similar in the two groups. Mean fiber size
      of each fiber type in the soleus was unaffected by centrifugation. In the MG, the
      fibers, expressing only type IIb MHC were smaller in the centrifuge compared to
      control rats. CONCLUSION: Although 2 weeks of chronic centrifugation at 2G
      resulted in a cessation of body growth, there was essentially no effect on the
      muscle masses or fiber size in either a slow or fast extensor muscle. These data
      suggest that periods of centrifugation may be beneficial in maintaining extensor
      muscle mass in an animal that is not growing at a normal rate e.g., during
      chronic unloading.

PMID- 9025803
TI  - Aircrew fatigue monitoring during sustained flight operations from Souda Bay,
      Crete, Greece.
AB  - BACKGROUND: Operational flight surgeons are often responsible for determining
      aeromedical readiness of aircrew members whose accumulated flight time exceeds
      standard limitations. Realizing that operational reports of excessive flight time
      in aircrew are limited, we used Rayman's 1975 study of fatigue during Cambodian
      airlift missions as a model to evaluate 42 U.S. Navy EP-3E aircrew members flying
      reconnaissance missions from Souda Bay, Crete, Greece. Measured parameters
      focused on information accessible to operational flight surgeons. METHODS: Hoping
      to identify early indices of fatigue, the aircrews were monitored using anonymous
      questionnaires, physiologic data (mean arterial pressure, pulse, pulse pressure),
      and hematologic measurements (CBC, sedimentation rate). RESULTS: As suspected, no
      physiologic parameter indicated early fatigue. However, some aircrew demonstrated
      small changes in measured visual phorias as compared to prior evaluations.
      Anonymous questionnaires and subjective evaluation of crewmembers appeared most
      valuable in assessing fatigue. CONCLUSION: Incorporating previously reported
      recommendations for fatigue surveillance, the Souda Bay experience is an example
      of successful fatigue monitoring in aircrews who accumulate flight time beyond
      standard restrictions.

PMID- 9025804
TI  - Lipid lowering therapy and military aviators.
AB  - This article discusses the role of the newer lipid lowering agents (statins and
      fibrates) for the treatment of hyperlipidemias in military aviators. Special
      emphasis will be on long-term safety and the effects of these drugs on CNS
      functions pertinent to aviators. We propose that these new lipid lowering agents,
      such as hydrophilic statins and newer fibrates are reasonably safe in aviators
      with restricted flying duties, subject to long-term surveillance by a specialist.

PMID- 9025805
TI  - Mefloquine versus doxycycline for malaria prophylaxis in intermittent exposure of
      Israeli Air Force aircrew in Rwanda.
AB  - BACKGROUND: The issue of the best chemoprophylaxis agent for aircrew to use
      against malaria is still not settled. METHOD: We studied the patterns of use of
      both doxycycline and mefloquine in aviators and other aircrew for 2 mo during
      biweekly flights from Israel to Rwanda with a few hours' visits. Some 28 aviators
      and 15 non-aviator aircrew were treated with doxycycline and mefloquine,
      respectively, less than 12 h before the first flight and up to 4 wk after the
      last return. RESULTS: No case of malaria occurred within or after the operational
      period. Compliance was better for mefloquine than for doxycyline for the full
      period of the operation (100% vs. 75%, respectively). The rate of side effects,
      mostly gastrointestinal, was higher for doxycycline (39% vs. 13%, respectively)
      and was related mainly to the frequency of administration (daily vs. weekly).
      CONCLUSION: In situations involving frequent intermittent short-term visits to
      areas with substantial risk of acquiring malaria, we conclude that aircrew can
      safely take weekly mefloquine as prophylaxis.

PMID- 9025806
TI  - Retinal detachment in U.S. Air Force flyers.
AB  - Retinal detachment is a serious ocular condition, even though 85% can be repaired
      permanently. Long-term complications include decreased or loss of vision,
      redetachment, visual field changes, and proliferative vitreoretinpathy. To assess
      the effect of retinal detachment on flying careers, we reviewed the records of
      all aviators with a rhegmatogenous retinal detachment who were examined by the
      Ophthalmology Branch of the Aerospace Medicine Directorate at the Armstrong
      Laboratory (formerly the USAF School of Aerospace Medicine) from 1967-1986. Of
      the 19 flyers, 12 were returned to flying duties; only 2 were disqualified for
      ocular reasons alone. In 10 flyers, the detachments were previously undiagnosed.
      Associated vitreoretinal pathology was common in both eyes (42%). All received
      some type of treatment. Redetachment occurred in 4 flyers, but the overall final
      reattachment rate was 95%. Final posttreatment visual acuities were 20/20 or
      better in 16 flyers. Treatment-induced myopia was common. Many flyers enjoyed
      long flying careers after detachment repairs.

PMID- 9025807
TI  - Coffee, tea, or frostbite? A case report of inflight freezing hazard from dry
      ice.
AB  - Occupational and recreational cold exposure is fairly well described in the
      literature. This is a case report of a passenger on a commercial airline flight
      who suffered third degree frostbile due to the attempted therapeutic use of a
      cold pack. This cold pack was offered by the flight attendant and consisted of a
      section of dry ice used for cooling in the galley. The resulting injury consisted
      of a full thickness cold injury of the left lumbar amounting to approximately
      1.5% TBSA (total body surface area). The occurrence of third degree frostbite due
      to a medicinally used ice pack such as this has not been noted in the past
      writings. The resulting injury, care and outcome of such an injury are described
      and discussed.

PMID- 9025808
TI  - Physiological training in Jordan.
AB  - The hypobaric chamber is designed as a teaching aid in providing orientation for
      some of the physiological stresses in flight. Reactions during chamber training
      vary from mild ear block to neurocirculatory collapse. This is a retrospective
      study on reactions from 1986-94 in the hypobaric chamber training unit at King
      Hussien Medical Centre in Jordan; 39 cases were reported among 705 trainees in a
      12-person rectangular hypobaric chamber. We analyzed the various reactions
      according to type, severity and altitude of occurrence. The most common reactions
      were found to be ear block (65%) and sinus block (25%). These were treated on the
      spot and followed for 48 h without sequelae. We did not have any moderate or
      severe reaction; we found that all reactions were minor, which reflects the
      efficacy of safety measures taken prior to and during training.

PMID- 9025809
TI  - Evaluation of repatriation parameters: an analysis of patient data of the German
      Air Rescue.
AB  - We investigated the medical history of 1468 patients of the German Air Rescue
      with regard to indications and rules that are used for the repatriation of sick
      or injured people by aircraft from abroad. Some 25.5% of the flights were
      domestic flights within Germany, 40.9% from the European continent, and 33.6%
      from outside Europe: North Africa, North America, the Middle and the Far East. Of
      the patients, 46% were non-surgical and 54% were surgical cases. The majority
      (90.3%) of international cases were flown home in ambulance airplanes (Learjet,
      Merlin); the remaining 9.7% were scheduled flights. The rate of false alert was 7
      10%. According to the National Advisory Committee for Aeronautics (NACA)
      classification, the majority of patients had moderate to serious illnesses. Some
      33% of the patients were repatriated purely on medical grounds with an
      accompanying doctor. The indications of 66% of the patients were a mixture of
      medical and social components. Lists of points are available on the basis of
      catalogues of medical and social indications.

PMID- 9025810
TI  - 42nd annual Louis H. Bauer Lecture. New challenges in prevention.

PMID- 9025811
TI  - Cases from the aerospace medicine residents' teaching file. Case #66. A pilot
      with Falciparum malaria.

PMID- 9025812
TI  - Type III decompression sickness.

PMID- 9025813
TI  - Performance of color-dependent air traffic control tasks as a function of color
      vision deficiency.
AB  - BACKGROUND: This experiment was conducted to validate the requirement for normal
      color vision in Air Traffic Control Specialist (ATCS) personnel who work at en
      route center, terminal, and Flight Service Station (FSS) facilities. METHODS: A
      data base was developed involving 121 individuals with normal color vision, 31
      simple and 44 extreme anomalous trichromats, and 48 dichromats; both protans and
      deutans were included. The performance of subjects with normal color vision was
      compared with the performance of individuals with various classifications of
      color vision deficiencies on a battery of color-dependent ATCS tasks. Simulations
      of the ATC color tasks concerned color coding in flight progress strips (at en
      route centers), aircraft lights and Aviation Signal Light indicator (in tower
      operations), and color weather radar (at FSS's). RESULTS: Errors were rare among
      normal trichromats. Mean errors were significantly higher at every level (degree)
      of color vision deficiency. Approximately 6% of color deficient subjects were
      able to perform ATC color tasks without error. The 6% were all from the simple
      anomalous trichromat category; all extreme anomalous trichromats and dichromats
      were prone to error on ATC tasks. CONCLUSIONS: We conclude that these findings
      provide support for the requirement of normal color vision in the initial medical
      screening of ATCS personnel.

PMID- 9025815
TI  - Endurance fitness and orthostatic tolerance.
AB  - BACKGROUND: Several lower body negative pressure studies conducted in recent
      years have suggested that aerobically fit individuals have poo-orthostatic
      tolerance (OT). HYPOTHESIS: There will be significant differences between OT of
      highly fit endurance runners and unfit individuals. METHODS: Subjects were 17 men
      and 17 women aged 29-42 yr who were administered two orthostatic tests (20 min
      standing) before, and 5 min following a VO2max test. There were 6 men and 6 women
      who were highly trained endurance runners with VO2max of 63 and 50 ml.kg-1.min-1
      for the men and women, respectively; 6 men and 6 women had average fitness
      (VO2max of 40 and 32 ml.kg-1.min-1, respectively), and the remaining 5 men and 6
      women had poor fitness (VO2max of 32 and 26 ml.kg-1.min-1, respectively).
      RESULTS: The trained men and women showed good OT before and after exercise,
      which was characterized by very low orthostatic heart rates (54 and 64 bpm
      before, 70 and 75 bpm after exercise, for the men and women, respectively);
      relatively large pulse pressures (PP); and a lack of any adverse subjective
      reactions. The untrained subjects' orthostatic heart rates were 30-40 bpm higher
      than in the trained subjects, (18 bpm higher after, vs. before exercise) their PP
      was narrower, and there were 7 cases of orthostatic weakness (dizziness, yawning)
      and 8 fainting episodes. (6 cases before, 9 cases after exercise). CONCLUSIONS:
      Aerobically fit individuals have good OT while unfit individuals show poor OT.
      Since the maintenance of good OT is important in the Space Shuttle flights,
      endurance training enhances crew/vehicle safety.

PMID- 9025814
TI  - Effects of head down tilt on hemodynamics, fluid volumes, and plasma Na-K pump
      inhibitor in rats.
AB  - BACKGROUND: Hindquarter suspension in rats has been used as a model of simulated
      weightlessness (SW) for ground based study of the effects of microgravity on the
      cardiovascular system (CVS). METHODS: Using this rat model of SW we tested the
      hypothesis that CVS deconditioning following spaceflight results, in part, from a
      decrease in the circulating concentration of sodium-potassium pump inhibitor
      (SPI). Control rats similarly prepared were not suspended. RESULTS: During the
      first hour of suspension, central venous pressure (CVP), blood pressure (BP),
      heart rate (HR), cardiac output (CO), plasma volume (PV), extracellular fluid
      volume (ECFV), urine output (UV), atrial natriuretic peptide (ANP), and the
      plasma level of SPI increased. Plasma renin activity (PRA) and myocardial Na+,
      K(+)-ATPase activity (NKA) decreased. By the end of 4 h of SW, the changes in
      CVP, BP, HR, ECFV, and UV persisted, but PV, plasma ANP and SPI, and myocardial
      NKA activity returned to control levels. By the end of 1 d of SW, ECFV and plasma
      SPI levels had decreased but the myocardial NKA had not increased. At day 4, CVP
      and BP were the same as in control sham treated rats. Plasma SPI levels were
      decreased at day 4 but the myocardial NKA was not different, whereas renal NKA
      was increased. At day 7, myocardial NKA and renal NKA were increased and vascular
      smooth muscle cell (VSMC) membrane potentials were hyperpolarized. CONCLUSIONS:
      These data indicate that prolonged SW causes a decrease in plasma SPI level
      which, by hyperpolarizing VSMC, may play a role in the CVS deconditioning seen in
      astronauts following spaceflight.

PMID- 9025816
TI  - Locomotion while load-carrying in reduced gravities.
AB  - Supporting the mass of a protective suit and portable life support system (PLSS)
      will impose an energy requirement on planetary astronauts. To design
      extravehicular protective equipment for planetary missions, scientists must learn
      more about human physical capabilities while load-carrying in reduced gravities.
      In this study, an underwater treadmill and weighting system were used to simulate
      reduced-gravity locomotion while load-carrying. The test matrix included 3
      gravity levels, 6 subjects, 2 locomotion speeds, and a range of load sizes.
      Energy expenditure, calculated from measured oxygen consumption, is positively
      correlated with gravity level, speed, and load size. The data are used to project
      that individuals in average physical condition will be able to walk for 8 h on
      the Moon while carrying up to 170% of their body mass without undue fatigue, and
      on Mars with up to 50% of their body mass. These approximate limits, especially
      for Martian gravity, may prove quite a challenge for designers of advanced
      protective systems. Requirements for regenerable and non-venting PLSS components
      have been driving the total projected masses of advanced PLSSs increasingly
      higher, perhaps beyond what is reasonable to carry. However, the larger mass can
      be beneficial in maintaining bone mass. Using Whalen's model (1988), the daily
      planetary walking times required to maintain bone mass were calculated for a
      range of carried load sizes. The calculated times were unattainably high,
      suggesting that some combination of loads carrying and supplemental bone
      maintenance measures will likely be required to maintain bone mass in reduced
      gravity environments.

PMID- 9025817
TI  - Microgravity effect on the vestibulo-ocular reflex is dependent on otolith and
      vision contributions.
AB  - BACKGROUND: We studied whether microgravity influences horizontal and vertical
      vestibulo-ocular reflex (VOR), and what the otolith contributes to VOR in the
      absence of gravity, in six cosmonauts during and after space missions. METHOD:
      VOR was elicited by active yaw and roll head movement at a frequency of about 0.2
      Hz. RESULTS: The various individual quantitative changes (increase, decrease, and
      left-right asymmetry) found in the horizontal VOR evoked by yaw head movements
      during the adaptation period to microgravity suggested central reprogramming of
      mechanisms controlling VOR; i.e., a non-specific effect of microgravity on VOR.
      At the same time, horizontal and vertical VOR's were recorded during roll head
      movements, which were not obvious before flight. In the consmonaut who
      participated in a long-term flight, the increased activity of vertical canals
      turned to unidirectional (downward) eye movements, independent of the head
      movement direction, lasting during the whole mission. These VOR changes probably
      resulted from the absent adequate otolith stimulation and reduced otolith
      influence upon semicircular canal function. CONCLUSIONS: Thus, a specific effect
      of microgravity on VOR was observed during roll head movements, when the
      interaction between semicircular canals and otoliths should be more pronounced,
      mainly in the vertical plane. The stability of the "space" pattern of
      interactions in the readaptation period depended on the time spent in
      microgravity. We suggest that in visual-vestibular interactions revealed in VOR
      evoked by head movements with open eyes, vision dominates when a conflict arises
      between "space" and "terrestrial" patterns of sensory interactions.

PMID- 9025818
TI  - Visual and vestibular components of motion sickness.
AB  - BACKGROUND: The relative importance of visual and vestibular information in the
      etiology of motion sickness (MS) is not well understood, but these factors can be
      manipulated by inducing Coriolis and pseudo-Coriolis effects in experimental
      subjects. HYPOTHESIS: We hypothesized that visual and vestibular information are
      equivalent in producing MS. The experiments reported here aim, in part, to
      examine the relative influence of Coriolis and pseudo-Coriolis effects in
      inducing MS. METHODS: We induced MS symptoms by combinations of whole body
      rotation and tilt, and environment rotation and tilt, in 22 volunteer subjects.
      Subjects participated in all of the experiments with at least 2 d between each
      experiment to dissipate after-effects. We recorded MS signs and symptoms when
      only visual stimulation was applied, when only vestibular stimulation was
      applied, and when both visual and vestibular stimulation were applied under
      specific conditions of whole body and environmental tilt. RESULTS: Visual stimuli
      produced more symptoms of MS than vestibular stimuli when only visual or
      vestibular stimuli were used (ANOVA F = 7.94, df = 1, 21 p = 0.01), but there was
      no significant difference in MS production when combined visual and vestibular
      stimulation were used to produce the Coriolis effect or pseudo-Coriolis effect
      (ANOVA: F = 0.40, df = 1, 21 p = 0.53). This was further confirmed by examination
      of the order in which the symptoms occurred and the lack of a correlation between
      previous experience and visually induced MS. CONCLUSIONS: Visual information is
      more important than vestibular input in causing MS when these stimuli are
      presented in isolation. In conditions where both visual and vestibular
      information are present, cross-coupling appears to occur between the pseudo
      Coriolis effect and the Coriolis effect, as these two conditions are not
      significantly different in producing MS symptoms.

PMID- 9025819
TI  - The effect of autogenic training and biofeedback on motion sickness tolerance.
AB  - BACKGROUND: Motion sickness is characterized by symptoms of vomiting, drowsiness,
      fatigue and idiosyncratic changes in autonomic nervous system (ANS) responses
      such as heart rate (HR) and skin temperature (ST). Previous studies found that
      symptoms of motion sickness are controllable through self-regulation of ANS
      responses and the best method to teach such control is autogenic-feedback
      (biofeedback) training. Recent experiments indicated that biofeedback training is
      ineffective in reducing symptoms of motion sickness or in increasing tolerance to
      motion. HYPOTHESIS: If biofeedback facilitates learning of ANS self-regulation
      then autogenic training with true feedback (TFB) should lead to better control
      over ANS responses and better motion tolerance than autogenic training with false
      feedback (FFB). If there is a relationship between ANS self-regulation and coping
      with motion stress, a significant correlation should be found between amounts of
      control over ANS responses and measures of motion tolerance and/or symptoms of
      motion sickness. METHOD: There were 3 groups of 6 subjects exposed for 6 weeks to
      weekly sessions of Coriolis stimulation to induce motion sickness. Between the
      first and second Coriolis sessions, subjects in the experimental groups received
      five episodes of autogenic training with either true (group TFB) or false (group
      FFB) feedback on their HR and ST. The control group (CTL) received no treatment.
      RESULTS: Subjects learned to control their HR and ST independent of whether they
      received true or false feedback. Learned control of ST and HR was not related to
      severity of motion sickness or subject's ability to withstand Coriolis
      stimulation following treatment. CONCLUSIONS: A lack of significant correlation
      between these variables suggested that subjects were not able to apply their
      skills of ANS self-regulation in the motion environment, and/ or such skills had
      little value in reducing symptoms of motion sickness or enhancing their ability
      to withstand rotations.

PMID- 9025820
TI  - Crewmember interactions during a Mir space station simulation.
AB  - BACKGROUND: Interpersonal problems may negatively affect crews on long-duration
      space missions. These problems stem from crewmember tension and its displacement
      to the outside monitoring personnel and from disruptions in crew cohesion and
      unclear leadership roles. HYPOTHESES: We hypothesized that crew tension and
      dysphoria would transiently increase following stressful events and be greater in
      the second half of a mission; that cohesion would be less during the second half
      of a mission; that tension and dysphoria would be displaced to the outside
      monitoring personnel; and that high levels of leader support and control would
      produce high levels of cohesion. METHODS: We tested these hypotheses during a 135
      d Mir space station simulation study in Moscow. At weekly intervals, the three
      crewmembers completed items from two group climate questionnaires, a mood
      questionnaire, and a log of stressful events. RESULTS: Contrary to expectations,
      there was significantly (p < 0.05) more total mood disturbance and tension during
      the first 9 wks than during the subsequent 10 wks of the simulation. Although
      levels of cohesion remained the same over time, cohesion scores dropped at a
      significantly greater rate during the last third of the seclusion. There was
      evidence for the displacement of tension and dysphoria to the outside monitoring
      personnel. There were significant correlations in the predicted direction between
      leader support and control and crew cohesion, as well as evidence of status
      leveling in the mission commander. CONCLUSIONS: Crewmember tension, cohesion, and
      leadership are important issues affecting people working in secluded
      environments, and they need to be studied further in space.

PMID- 9025821
TI  - Safety of commercial air travel following myocardial infarction.
AB  - BACKGROUND: Travelers occasionally suffer myocardial infarction (MI) while
      abroad. Existing guidelines recommend a 4- to 24-week convalescent period
      following MI before air travel should be permitted. HYPOTHESIS: Air travel may be
      undertaken safely in the early post-MI period. METHODS: The aeromedical transport
      records of two international medical assistance companies over a 3-yr period were
      reviewed. We identified 209 patients who suffered MI; 13 transported by private
      air ambulance were excluded. We reviewed the aeromedical transports of the
      remaining 196 adults carried on commercial aircraft between 3-53 d post-MI to
      investigate the safety of air travel in this group. Data were recorded regarding
      patient age; sex; location of MI; complications of MI; presence of medical
      escort; duration of flight(s); use of oxygen, medications, or cardiac monitoring
      during transport; and development of symptoms in flight. RESULTS: Within 7 d of
      their acute MI 3 patients (2%) were transported; 87 (44%) between days 8-14 post
      MI; 65 (33%) between days 15-21; 27 (14%) between days 22-28; and 14 (7%) more
      than 28 d post-MI. Some 187 patients (95%) were transported without incident; 9
      (5%) patients experienced symptoms requiring evaluation by the escorting
      physician. Of the 9, 6 problems occurred in patients being transported less than
      14 d post-MI. Symptoms resolved spontaneously or immediately after physician
      intervention in all but one case. CONCLUSION: International aeromedical transport
      of patients may be safely accomplished 2-3 wk after an acute MI when an
      accompanying physician is present. Recommendations for delaying travel more than
      4 wk after infarction are not supported by clinical experience and should be
      revised.

PMID- 9025822
TI  - The initial signs and symptoms of altitude decompression sickness.
AB  - BACKGROUND: With the potential for higher aircraft and cabin altitudes, the way
      in which altitude decompression sickness (DCS) presents continues to be of
      interest. The majority of previous papers on the symptomatology of DCS are
      retrospective reviews of patients treated hours or days post-exposure. The
      initial presentation while still at altitude is the form of DCS that aircrew must
      be able to recognize in order to respond correctly. This paper reports the
      initial manifestations of DCS that occurred during a series of prospective
      hypobaric chamber studies. These studies had been specifically designed to
      investigate DCS. METHODS: This paper presents a prospective analysis of DCS
      symptoms from 447 subjects, recorded over an 11-yr period at the Armstrong
      Laboratory (AL), and is an attempt to provide an accurate representation of the
      initial presentation of altitude DCS. RESULTS: Of the 447 cases, 83.2% had
      musculoskeletal involvement, 2.7% had chokes, 2.2% skin manifestations, 10.8%
      paresthesia, and 0.5% frank neurological features. CONCLUSIONS: The most common
      presenting feature was musculoskeletal, with knee pain predominating (occurring
      in 70% of these cases). A very low incidence of neurological features was seen in
      the AL database, which was in contrast to data from many other sources. Reasons
      for this difference may include the use of preoxygenation and the policy of
      prompt recompression upon symptom development at AL. There is also the
      possibility that individuals in the training and operational environments are
      more likely to report frank neurological involvement than other forms of DCS.

PMID- 9025823
TI  - Percutaneous transluminal coronary angioplasty (PTCA): long-term outcome and
      aeromedical implications.
AB  - BACKGROUND: Currently U.S. Air Force aviators are permanently disqualified from
      all military flying duties after PTCA. HYPOTHESIS: We wondered if a low risk
      group of post-PTCA patients was identifiable from the literature, such that
      trained aviators who met the criteria for such a group could be safely returned
      to military flying duties. METHOD: We reviewed the PTCA literature from 1978-93
      for long-term outcome (cardiac events) and patient characteristics that might
      affect outcome. Cardiac events were cardiac death, myocardial infarction (MI),
      and need for bypass surgery or repeat PTCA due to restenosis or progression of
      coronary artery disease (CAD). RESULTS: All patients were at risk for restenosis,
      the rate being highest in the first year post-PTCA (17-34%), and 10-40% of
      asymptomatic patients had restenosis. Noninvasive tests during the first 12 mo
      missed 25-54% of significant restenoses found by angiography. Beginning 1 yr
      after successful PTCA, cardiac event rates (excluding angina pectoris) were 2.4
      4.1% yr, as opposed to < 1%/ yr (including angina) in our asymptomatic,
      untreated, mild-moderate CAD aviator population. The late annual event rate did
      not decline in over 5 yr of follow-up. Significant CAD progression in other sites
      or vessels occurred in 39-45% of asymptomatic patients by 5-8 yr; 13-43% of
      successful PTCA survivors were experiencing angina 3-6 yr post-PTCA. None of the
      following patient characteristics lowered the event rates: absence of symptoms
      before or after PTCA, PTCA in single-vessel disease, age < 40 at time of PTCA,
      post-PTCA lesion < or = 30%, and lack of prior MI. CONCLUSION: No low risk
      subgroup of patients or safe waiting period post-PTCA could be identified by
      literature review. We cannot recommend return to any type of military flying
      duties at any time after PTCA because of the significant and steady rate of
      serious cardiac events.

PMID- 9025824
TI  - Intracerebral bleed, retinal detachment, cataract removal, and intraocular lenses
      in an Army aviator.
AB  - A 54-yr-old U.S. Army Reserve helicopter pilot was evaluated at Brooks AFB, TX
      for a flying waiver with a history of intracerebral hematoma, superior oblique
      palsy, rhegmatogenous retinal detachment and bilateral cataract extractions with
      intraocular lens replacements. The USAF has waivered flyers with category 5
      severe head injury (includes intracerebral bleed) in 7 (44%) of 16 cases
      evaluated and submitted after a 5-yr uneventful observation period, but never
      with an intracerebral bleed (0 of 3). Flyers with rhegmatogenous retinal
      detachment have been cleared for a waiver by ophthalmologists in 40 (89%) of 45
      cases: the USAF ultimately granted 28 (62%) of the 45 flyers waivers with the
      others denied for additional diagnoses. Of the 45 detachments, 17 (38%) were
      asymptomatic and discovered during routine eye evaluation. Increased "G" exposure
      has not been shown to increase the risk of either retinal detachment or
      intraocular lens displacement. Of 54 intraocular lenses in the USAF Study Group,
      50 (93%) are located in the posterior chamber. Waivers have been granted for 38
      (86%) of 44 flyers with intraocular lens replacements; only 3 (7%) of 44 have
      been denied waivers for ophthalmological complications. The preferred cataract
      surgery for aviators is extracapsular cataract extraction with placement of a
      posterior chamber intraocular lens, yielding the best visual results with fewest
      complications. This pilot was denied waiver recommendation because his
      neurological observational period had not yet lasted 5 yr, although he would have
      received a favorable recommendation for his ophthalmological diagnoses.

PMID- 9025825
TI  - Medical guidelines for air travel. Aerospace Medical Association, Air Transport
      Medicine Committee, Alexandria, Va.

PMID- 9025826
TI  - Understanding cardiac development through the perspective of gene regulation and
      gene manipulation.
AB  - Cardiovascular malformations affect about 1% of newborns, yet much remains to be
      learned about the pathogenesis of these defects. Advances in understanding some
      of the molecular events involved in regulating cardiac morphogenesis are
      providing a new perspective with which to approach complex issues and questions
      related to congenital heart disease. More important, this new information
      provides not only unique opportunities for developing specific experimental
      models of congenital heart disease through direct genetic manipulation but also
      the basis for developing ways of therapeutically manipulating cardiac gene
      expression for some form of heart disease. This review presents recent advances
      in the understanding of the molecular aspects of cardiac development and how this
      information can be used to manipulate cardiac gene expression during development.

PMID- 9025827
TI  - Mucin histochemistry of the developing gastroesophageal junction.
AB  - Mucin histochemistry was performed on the squamocolumnar junction (Z-line) of the
      gastroesophageal region of 49 autopsied previable fetuses, stillbirths, infants,
      and young children, using alcian blue pH 2.5/periodic acid-Schiff (PAS) and
      alcian blue pH 1.0/PAS stains. Sialylated and neutral mucins were present in most
      and sulfated mucin in many cases. In only one fetus was a heterotopic focus of
      goblet cells found in the distal esophagus. This study confirms that the presence
      of acidic mucins in columnar epithelium, without goblet cells, at the Z-line and
      adjacent cardia is common in this age group. Undue reliance on mucin stains to
      identify metaplastic columnar epithelium, in the absence of goblet cells, may
      result in overdiagnosis of Barrett's esophagus in children.

PMID- 9025828
TI  - Role of the placenta in perinatal pathology (revisited).
AB  - This article on the placenta includes considerations of chorioamnionitis,
      villitis, preeclampsia, and other low placental blood flow states and aspects of
      the circulating lupus anticoagulant syndrome. The author explains that, although
      gross and microscopic placental findings document placental features at one point
      in time, they also reflect ongoing pathophysiologic changes. Pathogenetic
      relationships between placental pathology, fetal hypoxia, intrauterine growth
      retardation, and cerebral palsy are discussed. The reader will learn that low
      placental blood flow states and chorioamnionitis are important means by which
      endothelins may eventually participate in the production of placental and fetal
      vasoconstriction and critical hypoperfusion. The author explains means by which
      reduced umbilical, placental, and fetal blood flow can result from chronic fetal
      exposure to meconium, meconium-induced vasoactivity, and ultimate vascular
      necrosis. Clinically important complications therein may include anoxic-ischemic
      neuronal necrosis in the brain, necrotizing enterocolitis, and ischemic lesions
      in the fetal heart, lungs, kidneys, and liver. The article includes a review of
      nucleated red blood cells that most often signify chronic fetal hypoxia rather
      than infrequent acute intrapartum asphyxia. The reader will also find information
      on chorangiosis (placental villous capillary hypervascularity), an important sign
      of placental malperfusion and very long-standing fetal hypoxia.

PMID- 9025829
TI  - Fine-needle aspiration of solid and papillary cystic tumor of the pancreas.
AB  - Solid and papillary cystic tumors of the pancreas are relatively rare tumors that
      occur in adolescent and young adult women. A case is presented in which
      preoperative diagnosis was made by fine-needle aspiration biopsy obtained under
      computed tomographic guidance. The cytologic smears were characterized by
      branching, papillary clusters of cells having a thin, well-defined, fibrovascular
      core and surfaced by multiple layers of cells. Sheets of cells were also present.
      The tumor cells had small, round to oval nuclei with finely stippled chromatin
      and an occasional small nucleolus. The nuclear membrane was delicate and nuclear
      infolding was frequent. The cytoplasm was scant and cell borders were indistinct.
      Mitotic figures were notably absent. The diagnosis was confirmed histologically
      following surgical resection. As this tumor has a favorable prognosis with
      complete surgical removal, fine-needle aspiration can play an important role in
      preoperative planning by distinguishing it from other pancreatic lesions with
      significantly different prognosis and treatment. Therefore, pediatric
      pathologists should be familiar with the cytologic manifestations of this tumor.

PMID- 9025830
TI  - Aspiration cytopathology of lymphoblastic lymphoma and leukemia: the MCV
      experience.
AB  - Malignant lymphoma, lymphoblastic type (LL), and acute lymphoblastic leukemia
      (ALL) are two well-known pediatric malignancies whose diagnoses are typically
      established by surgical tissue biopsy and/or bone marrow examination. The status
      of fine-needle aspiration (FNA) biopsy in the diagnosis and management of these
      lymphoblastic malignancies is controversial. We present our experience from the
      past 7 years using FNA in children from 10 months to 15 years (mean age 10.5
      years) of age with lymphoblastic cancers; in addition, two adult patients with
      ALL are included. Superficial FNA was performed in 16 cases (one patient had two
      aspirations 16 months apart). Eight patients were diagnosed with LL, six with
      ALL, and the one patient with two separate aspirates had lymphoblastic
      transformation of chronic myelogenous leukemia (CML). Five patients presented
      with the superior mediastinal syndrome. Sites of FNA included lymph node (nine
      cases), parotid gland (one), and soft tissues of the neck (four), buttock (one),
      and forehead (one). There were no complications from FNA. Except for one case
      (case 8), the patients with ALL and CML were previously diagnosed and treated for
      their disease, and FNA was performed primarily for the detection of disease
      recurrence. Conversely, in all eight children with LL, FNA was performed as the
      initial procedure to establish a primary diagnosis in previously well
      individuals. All eight LL patients responded-some dramatically-to chemotherapy.
      Two patients with LL and one with lymphoid blast crisis arising in CML had
      subsequent surgical biopsies that confirmed the FNA diagnosis. Immunophenotyping
      performed from 15 of 16 aspirates confirmed the T cell derivation of all cases of
      LL and 4 of 6 of ALL. Two of the ALL cases had a pre-B cell phenotype. Sufficient
      cells were obtained by FNA for flow cytometric DNA analysis in 9 of 16 cases. All
      cases but one were diploid, and 6 of 9 showed a high (> 6%) S phase. Our
      experience suggests that, when combined with immunologic phenotyping, definitive
      initial pathologic diagnosis of LL and recurrent ALL is possible and preferable
      using only aspiration cytopathology. It should be considered as part of the
      initial evaluation and management whenever a mass lesion appears in a child with
      a suspected lymphoblastic neoplasm. It can preclude the need for a surgically
      procured piece of tissue in those with a mediastinal mass and the superior
      mediastinal syndrome.

PMID- 9025831
TI  - Hepatoblastoma in a child with trisomy 18: cytogenetics, liver anomalies, and
      literature review.
AB  - A 26-month-old female with trisomy 18 and repaired omphalocele died of metastatic
      disease after resection of hepatoblastoma (HB) at 21 months of age. Four other
      cases (three of them published) suggest that the association of trisomy 18 and HB
      may be nonrandom. Karyotype abnormalities of the tumor in our case included
      duplication of 2q and +20, reported previously in HB arising in patients with
      normal karyotype. Antecedent growth disturbance of liver, either intrinsic
      (abnormal lobation) or related to contiguous extrinsic anomalies such as
      omphalocele or local diaphragmatic hypoplasia and possibly augmented by unusual
      sensitivity to noxious environmental agents, may predispose to hepatoblastoma in
      trisomy 18. Longevity in trisomy 18 predisposes to both hepatoblastoma and Wilms
      tumor, possibly by a shared pathway.

PMID- 9025832
TI  - Mitochondrial enlargement and crystalloid matrix arrays: distinctive finding in
      childhood portal hypertension due to cavernous transformation of the portal vein.
AB  - Elongated, enlarged mitochondria with crystalloid matrix arrays were discovered
      in periportal hepatocytes in 11 of 12 children (age 6 to 15 years) with portal
      hypertension, minimal alterations on light microscopy, and cavernous
      transformation of the portal vein. Eleven of the children were clinically well
      before onset of symptoms, one was anemic with megaloblastic bone marrow, and a
      second had undergone renal transplantation. Minimal findings by light microscopy
      included slight portal fibrosis (six cases), pericentral venular fibrosis (one
      case), mild, patchy sinusoidal sclerosis (one case), central venular and
      sinusoidal dilatation (two cases), and mild hepatocellular lipid accumulation
      (one case). Four were judged normal by routine histologic examination. Subtle
      depletion of periportal hepatocellular glycogen was present in six. In 10, subtle
      striation or granularity of periportal hepatocyte cytoplasm was visible with high
      magnification light microscopy. Although similar mitochondria are seen
      sporadically in hepatocytes in diverse settings, enlarged mitochondria with
      crystalloid matrix inclusions have not been previously reported as a uniform
      feature in children with portal hypertension due to cavernous transformation of
      the portal vein and minimal other hepatic alteration. It is postulated that the
      mitochondria are adapting in response to an abnormal metabolic milieu created by
      hemodynamic alterations.

PMID- 9025833
TI  - Microangiopathic glomerulopathy in children with sickle cell anemia.
AB  - We studied kidney biopsy specimens from three children with sickle cell anemia
      and microangiopathic glomerulopathy. One child also had cyanotic congenital heart
      disease. Laboratory evaluation revealed proteinuria and normal serum creatinine
      in all and normal serum complement in two of the three children at the time of
      biopsy. In all biopsies, glomeruli were enlarged with diffuse hypercellularity
      and focal segmental mesangial interposition; capillary loop lumens were congested
      with sickled erythrocytes. Immune labeling identified segmental immunoglobulin G,
      C3, and properdin over the glomerular capillary loop walls in each case.
      Ultrastructurally, the subendothelial zone of the glomerular basement membrane
      was widened with new lamina densa formation with focal mesangial interposition.
      The glomerular lesion we describe in these children may be due to endothelial
      injury related to the altered erythrocytes, glomerular hemodynamics, and the
      hypercoagulable state characteristic of sickle cell disease.

PMID- 9025834
TI  - Aicardi syndrome: a morphologic description with particular reference to
      intracytoplasmic inclusions in cortical astrocytes.
AB  - Aicardi syndrome is characterized by agenesis of the corpus callosum, infantile
      spasms, and ocular anomalies. Very few morphologic descriptions have been made of
      the central nervous system of children with this syndrome. We performed a
      postmortem examination of the brain of a 13-year-old girl with clinically well
      documented Aicardi syndrome. Gross examination revealed a small brain (745 g)
      with the right cerebral and cerebellar hemispheres smaller than the left. There
      was agenesis of the corpus callosum, and ectopic gray matter was scattered
      throughout the cerebral hemispheres. Both choroid plexus and arachnoid cysts were
      present. Microscopic examination revealed indistinct cortical layering and
      multiple foci of ectopic gray matter. The cerebellar sections were altered by
      focal atrophy with gliosis and Purkinje cell dropout. Multiple sections of
      cerebrum contained astrocytes with coarse, paranuclear, eosinophilic inclusions.
      Electron microscopy, immunohistochemistry, and special stains further defined
      these inclusions, which we speculate represent a degenerative process.

PMID- 9025835
TI  - Maternal floor infarction in autoimmune disease: two cases.
AB  - Two cases of maternal floor infarction in women with autoimmune antibody
      production to various antigens are presented. We speculate that maternal floor
      infarction could be produced by antibodies directed against the placental
      urokinase plasmin system.

PMID- 9025836
TI  - Perinatal pathology of interhemispheric cyst with thinned posterior corpus
      callosum: four cases.
AB  - This paper presents four posterior, interhemispheric cerebral cysts found at
      perinatal autopsy. All cysts appeared to attenuate the overlying posterior corpus
      callosum. All had a base over the roof of the third ventricle and midbrain with a
      lining that resembled tela choroidea with the choroid plexus tufts projecting
      into the lumen of the cyst. Three cases had enlargement of the lateral
      ventricles. One case had complete communication between the cyst and the
      posterior lateral ventricles reminiscent of a holoprosencephaly confined to the
      posterior telencephalon. One case demonstrated a complete VATER association and
      two others had some features of the VATER association. We hypothesize that this
      latter relationship suggests an origin for the cysts during blastogenesis.

PMID- 9025837
TI  - Ultrashort segment Hirschsprung's disease: a case report.
AB  - Hirschsprung's disease (HD) or congenital aganglionosis usually presents with
      involvement of the rectosigmoid, except for a small percentage of the ultrashort
      segment cases in which dysfunction is limited to the area of the anal sphincter.
      However, the diagnostic criteria for ultrashort segment HD are the subject of
      some controversy. The reported case illustrates the gross and microscopic anatomy
      of a documented case of ultrashort segment HD and helps define the proper biopsy
      technique and confirm previously established criteria for accurate diagnosis. It
      is suggested that modification of criteria to allow up to a 4-cm segment of
      aganglionosis for the diagnosis of ultrashort segment HD would eliminate some of
      the current ambiguity. Functional disorders of the and sphincter should be
      considered separately.

PMID- 9025838
TI  - Alexander disease: a case report and review of the literature.
AB  - Alexander disease (AD) is a rare progressive lethal leukodystrophy usually
      affecting infants and characterized by progressive failure of central myelination
      and accumulation of Rosenthal fibers (RFs) in astrocytes. Despite strong male
      predilection and infrequency of involved siblings, an autosomal recessive mode of
      inheritance is presumed. We report a typical case of infantile AD with imaging
      studies, a complete autopsy, and a critical literature review. Recent studies of
      AD have identified several stress proteins plus glial fibrillary protein as major
      constituents of RFs but have not clarified the basic defect. Advances in
      understanding of astrocyte function suggest an important role in the process of
      myelination that may be interrupted in AD. The nosology of putative juvenile
      onset and adult-onset examples continues to be uncertain.

PMID- 9025839
TI  - Inherited ichthyoses: a review of the histology of the skin.
AB  - The histology of skin biopsies from 46 cases of different forms of congenital
      ichthyosis was reviewed. Sections were examined for hyperkeratosis, follicular
      keratosis, appearance of the granular layer, epidermal thickness, tonofilament
      clumps, epidermal vacuolation, spongiosis, bullae and dyskeratosis, appearance of
      the basal layer, inflammation, mitoses, and adnexae. A detailed description of
      the histological features of each type of ichtnyosis studied is presented. Some
      ichthyoses can be recognized on routine hematoxylin and eosin staining (bullous
      ichthyosiform erythroderma, Netherton's syndrome, and neutral lipid storage
      disease); some forms require frozen sections to demonstrate fat (neutral lipid
      storage disease) or enzyme activity (Sjogren-Larsson syndrome). Protein
      electrophoresis and enzymology are necessary for X-linked recessive ichthyosis. A
      close liaison with the clinicians is essential for the diagnosis of all types of
      ichthyosis, and combined studies including routine histopathology, electron
      microscopy, and frozen sections may be required for the diagnosis.

PMID- 9025840
TI  - EWS/FLI-1 fusion transcript detection and MIC2 immunohistochemical staining in
      the diagnosis of Ewing's sarcoma.
AB  - Ewing's sarcoma (ES) and other primitive peripheral neuroectodermal tumors
      (pPNETs) can present a significant diagnostic problem, as they may
      morphologically resemble other small round cell tumors (SRCTs) of childhood.
      However, ES/pPNET is known to carry a characteristic t(11;22)(q24;q12), the
      detection of which may aid diagnosis. The recent identification of the EWS and
      FLI-1 genes flanking the translocation break point has enabled reverse
      transcriptase-polymerase chain reaction (RT-PCR) to be used to detect the
      putative chimeric transcription factor mRNA produced by the fusion gene. We have
      assessed the RT-PCR method of detection by examining 40 cases of ES for the
      presence of EWS/FLI-1 transcripts. Twenty-six (76%) of the 34 cases with intact
      mRNA yielded fusion transcripts. Four different transcript sizes were detected
      and two tumors contained two transcripts of different size. No transcripts were
      detected in a control group of non-ES/pPNET SRCTs. Eight cases with intact mRNA
      were transcript negative. The MIC2 cell surface antigen, which is reported to be
      present in over 95% of ES/pPNETs, was present in 32 of 33 tumors (97%), including
      all 24 EWS/FLI-1 transcript-positive cases examined. Hence MIC2 is a useful
      screen for ES, with RT-PCR detection of t(11;22) being the optimal method for
      confirming the diagnosis.

PMID- 9025841
TI  - Dystrophinopathy in isolated female patients with muscular dystrophy.
AB  - Immunohistochemical examination of dystrophin is suggested as a useful method for
      diagnosing Duchenne carriers for genetic counseling, in the absence of an index
      case. This study included 17 females with an age range of 6 to 17 (mean 11.97 +/-
      3.81) years and without a family history of Duchenne muscular dystrophy but with
      varying symptoms of muscle disease, high creatine kinase concentrations,
      myopathic muscle biopsies, and normal karyotype. Clinical severity was scored
      according to neurological findings. Muscle ultrasonography, cardiac evaluation,
      and pathologic examination were done. Dystrophinopathy was detected in six cases
      (35.3%). All of these cases included 8-33% partially dystrophin-deficient fibers
      and four of them also had 2-23% deficient fibers. Three cases revealed a mosaic
      pattern of dystrophin staining. Neither age nor clinical findings correlated with
      dystrophinopathy; creatine kinase concentrations correlated significantly,
      however.

PMID- 9025842
TI  - Human papillomavirus (HPV)-associated neonatal giant cell hepatitis (NGCH).
AB  - Neonatal giant cell hepatitis (NGCH) is a clinicopathological syndrome that has
      been related to perinatal infections and metabolic disorders. In a great number
      of cases no apparent etiology has been found. To characterize the possible
      relationship between human papillomavirus (HPV) and idiopathic NGCH (INGCH) we
      analyzed paraffin-embedded hepatic biopsies from seven cases of INGCH for the
      presence of both HPV and cytomegalovirus (CMV) DNA. Clinically, jaundice,
      detected within the first 3 days of life (except in one case), and raised levels
      of serum transaminases and bilirubin, mainly the direct fraction, were recorded
      in all. Follow-up of six patients revealed complete recovery. In a "blind"
      experiment, samples were studied along with appropriate controls [2 cases of CMV
      hepatitis, one case of postinfantile GCH, 12 cases of juvenile laryngeal
      papillomatosis (JLP), and 5 normal neonatal liver samples] by polymerase chain
      reaction (PCR). All DNA samples from INGCH consistently showed positive HPV DNA
      amplification. This was also found in the samples from postinfantile GCH and JLP.
      In addition, a second biopsy performed 11 months later in one of the cases of
      INGCH revealed scattered multinucleated hepatocytes and was still positive for
      HPV DNA. CMV-DNA was detected only in the cases of CMV hepatitis. All five normal
      livers were negative for HPV and CMV-DNA. These data seem to indicate that HPV
      may be closely related to a subset of "idiopathic" NGCH with good outcome.

PMID- 9025843
TI  - Histopathology of the liver in histiocytosis syndromes.
AB  - Liver biopsies were studied in 47 cases representing various histiocytosis
      syndromes. These included 32 cases of hemophagocytic syndrome, 11 cases of
      Langerhans cell histiocysis (LCH), and 4 cases of other histiocytic disorders.
      All cases of hemophagocytic syndrome, except one with cytomegalovirus infection,
      displayed portal lymphohistiocytic infiltrates dominated by T lymphocytes.
      Activation of the hepatic mononuclear phagocytic system (MPS), evidenced by
      enlarged von Kupffer cells, some of which were hemophagocytic, was seen in 28
      cases of hemophagocytic syndrome. Endothelial enlargement, minor degrees of
      hepatocellular degeneration, and steatosis were also noted. Ten of the 11 cases
      of LCH also showed activation of the MPS. It was the only lesion in two biopsies.
      Seven cases demonstrated nonspecific "triaditis." In three this was associated
      with cholangiocentric and random acinar histiocytic lesions. Evidence of
      activation of the MPS was also observed in both cases of Rosai-Dorfman disease
      and was accompanied by acinar histiocytic lesions in one and triaditis in the
      other. Likewise, both cases of juvenile xanthogranuloma showed activation of the
      MPS and focal granulomatous lesions. It is concluded that activation of the MPS
      is a common feature of liver disease in histiocytosis syndromes and that hepatic
      enlargement may be the result of this process instead of, or in addition to, the
      liver lesions known to be featured in these disorders. Hepatic lesions of the
      various histiocytosis syndromes resemble typical lesions in other sites and, in
      some instances, are accompanied by nonspecific changes. These nonspecific changes
      may occur in the absence of lesions that are diagnostic or typical of the
      particular histiocytosis syndrome. The location and character of hepatic lesions
      are important factors in the significance of liver involvement.

PMID- 9025844
TI  - Molecular analysis in the diagnosis of pediatric lymphomas.
AB  - Thirty-five pediatric lymphomas were categorized as either Burkitt's lymphoma
      (BL), lymphoblastic lymphoma (LL), or large cell anaplastic lymphoma (LCAL) by
      histological and immunophenotypic methods. They were further characterized by
      molecular analysis of their antigen receptor genes. Southern blot (SB) and
      polymerase chain reaction (PCR) techniques were compared in the detection of
      immunogloblin heavy chain gene (IgH) rearrangement. T cell receptor beta (TCR
      beta) rearrangements were analyzed by SB and TCR gamma gene rearrangements by
      PCR. The PCR method of IgH and TCR gamma gene analysis was preferred to the SB
      methods, because there were fewer equivocal results in IgH gene analysis, TCR
      gamma rearrangement was more frequently detected than TCR beta in both
      lymphoblastic and large cell anaplastic lymphomas, and the PCR technique was more
      rapid, required less DNA, and could be used with archival material. In addition,
      analysis of IgH gene rearrangement by PCR was more specific for assessing B cell
      lineage. Although most of the molecular data were easily interpreted, occasional
      ambiguous results were seen due to genetic events other than antigen receptor
      gene rearrangement affecting the genetic analysis. Thus, it is imperative to
      interpret these genetic data in the context of adequate morphological and
      immunophenotypic analysis.

PMID- 9025845
TI  - Testicular sex cord-stromal tumors in children: clinicopathologic study of
      sixteen children with review of the literature.
AB  - Sex cord-stromal tumors of the pediatric testis present diagnostic and
      therapeutic challenges. This study examines the clinicopathologic features of 16
      testicular sex cord-stromal tumors from children less than 18 years of age. Four
      juvenile granulosa cell tumors and five tumors of Sertoli or incomplete
      differentiation in this study had high mitotic rates and/or sarcomatoid areas
      that suggested malignancy, but none of these children developed recurrence or
      metastases. Some of these tumors had been initially misdiagnosed as yolk sac
      tumors or rhabdomyosarcomas because of the presence of areas superficially
      resembling these neoplasms. These morphologic pitfalls have received little
      attention in the literature. Even incompletely differentiated sex cord-stromal
      tumors have at least focal areas characteristic of juvenile granulosa or Sertoli
      cell differentiation. In addition, immunohistochemical negativity for alpha
      fetoprotein, muscle specific actin, and desmin are useful for ruling out yolk sac
      tumor and rhabdomyosarcoma. Four patients had Leydig cell tumors and three had
      large cell calcifying Sertoli cell tumors. Children with Leydig cell tumors are
      not at risk for metastasis, but children with large cell calcifying Sertoli cell
      tumors are at risk for endocrine syndromes as illustrated by one of our cases.
      The differential diagnosis of these tumors is also discussed.

PMID- 9025846
TI  - Polymerase chain reaction amplification of archival material for parvovirus B19
      in children with transient erythroblastopenia of childhood.
AB  - The relationship between transient erythroblastopenia of childhood (TEC) and
      parvovirus B19 infection remains uncertain. Large series using primarily
      serologic evaluation have not shown an association, whereas smaller series have
      reported parvovirus B19 infection in such patients. Further, parvovirus DNA or
      antigen has been detected in some patients seronegative for the virus at
      presentation. Polymerase chain reaction (PCR) amplification has never been used
      to evaluate patients with TEC for parvovirus B19. We used the PCR in an attempt
      to detect parvovirus B19 in DNA extracted from archived bone marrow coverslips of
      16 patients diagnosed with TEC. The patients ranged in age from 3 to 23 months
      and presented with a mean hemoglobin value of 5.4 g/dL. Sixty-nine percent were
      neutropenic and none was thrombocytopenic. None of the patients had histologic
      evidence of parvovirus B19 infection in the bone marrow. DNA amplification for
      parvovirus B19 was negative in each case. In contrast, parvovirus B19DNA was
      amplified from DNA isolated from archived bone marrow coverslips of a patient
      with known parvovirus B19 infection, indicating that the PCR assay was
      sufficiently sensitive to detect virus from archieved bone marrow coverslips.
      Review of the literature indicates that the patients with parvovirus-associated
      TEC are generally older and often present with concomitant thrombocytopenia,
      whereas patients with parvovirus B19-negative TEC are younger and present without
      thrombocytopenia, similar to the patients in our study. Our results suggest that
      parvovirus B19 is not the cause of anemia in the young patient with typical
      features of TEC. Rather, parvovirus B19 infection of older, previously healthy
      children may occasionally cause a protracted anemia, often with thrombocytopenia,
      which may be diagnosed by some as TEC.

PMID- 9025847
TI  - Oxalate nephrocalcinosis: a study in autopsied infants and neonates.
AB  - A review of renal histology from 44 neonatal and pediatric autopsies, all with
      documented intensive hospital courses, identified 8 cases showing varying degrees
      of microscopic calcium deposition. Histochemical and x-ray spectroscopic
      microanalysis showed that all eight cases contained intratubular deposits of
      calcium oxalate, and two cases contained both oxalate and phosphate microliths.
      The spatial arrangement of the deposits appeared to vary with the density of
      deposition. A control group of 68 non-intensively treated cases (stillbirths and
      sudden infant death syndrome cases) showed rare calcium phosphate microliths but
      none had oxalate crystals. Infantile nephrocalcinosis is little understood and is
      poorly documented in the current literature. This study may contribute to the
      understanding of this entity and may be useful in guiding stratagems to prevent
      its occurrence.

PMID- 9025849
TI  - Liver and brain iron deficiency in newborn infants with bilateral renal agenesis
      (Potter's syndrome).
AB  - Significant changes in fetal iron status potentially occur in pregnancies in
      which reduced fetal nutrient delivery is severe enough to result in intrauterine
      growth retardation (IUGR), particularly if chronic fetal hypoxia is also present
      and increases fetal iron demand for hemoglobin synthesis. Neonates rarely die
      following IUGR secondary to maternal preeclampsia, but bilateral renal agenesis,
      which is also characterized by reduced maternal-fetal blood flow, late gestation
      placental failure, and IUGR, is uniformly fatal. We measured neonatal liver iron
      concentration, as an assessment of fetal storage iron status, and heart and brain
      iron concentrations, as assessments of nonheme tissue iron status, in 11 infants
      who died in the neonatal period of bilateral renal agenesis, and compared them
      with values for gestational age-matched control infants whose gestation was not
      complicated by fetal growth retardation or hypoxia. Stainable nonheme iron in the
      hepatocytes was significantly reduced in all and completely absent in 8 of the 11
      cases of renal agenesis (P < .001 compared with control). The mean +/- SEM liver
      iron concentration of the bilateral renal agenesis group (999 +/- 218
      micrograms/g dry tissue weight) was 26% of the control value (3894 +/- 548
      micrograms/g dry tissue weight; P < .001). Brain iron concentration was also
      lower in the group with bilateral renal agenesis (109 +/- 17 vs. 161 +/- 19; P =
      .015) and was correlated with liver iron concentration (r = .47; P = .03). Heart
      iron concentrations were similar in the two groups. Nine of the subjects with
      bilateral renal agenesis had placental weights below the fifth percentile for
      gestational age. The bilateral renal agenesis group had a lower mean birth weight
      (P < .001) and had a higher prevalence of fetal growth retardation (55% vs. 0%; P
      < .001). We conclude that infants with bilateral renal agenesis are at risk for
      severe iron deficiency of storage and nonstorage tissues. Liveborn infants with
      nonfatal fetal conditions characterized by significant restriction of maternal
      fetal blood flow may also be at significant risk for postnatal iron deficiency.

PMID- 9025848
TI  - Prostaglandin E1-induced hyperostosis: clinicopathologic correlations and
      possible pathogenetic mechanisms.
AB  - Prostaglandin E1 (PGE1) causes skeletal hypertrophy, a phenomenon noted when it
      is administered for several weeks to maintain ductus arteriosus patency in
      neonates with congenital heart disease. This effect, a dose-dependent and
      reversible hyperostosis, was described radiologically as bone within bone, but
      skeletal histopathology was not studied. We compared postmortem gross,
      radiological, and histological bone findings for untreated controls and term
      gestation infants after 4, 27, and 56 days of continuous 0.1-0.2 microgram/kg/min
      PGE1. Bone was not significantly different from controls after 4 days of PGE1.
      Radiographs were negative after 27 days, but femoral cortex showed early
      periosteal osteoblast proliferation. At 56 days of PGE1, there was severe,
      radiologically apparent neocortex formation in tubular, rib, and scapular bones.
      Corresponding sections of femoral shaft revealed distinctive histopathology with
      thickened periosteum and fibrocartilage-like tissue covering an exuberant
      neocortex of closely aligned, gracile, woven bone trabeculae. Paratrabecular
      stroma contained ectatic capillaries orthogonally oriented to the periosteum,
      suggesting that a vascular reaction to PGE1 is important in the observed effect.
      The native cortex was partially resorbed; because it is stress shielded by the
      neocortex and no inflammation was present, this was interpreted as a secondary
      effect. We conclude that PGE1-associated paracortical bone hypertrophy is
      distinct from inflammatory processes and that its early stages may not be
      apparent radiologically. Moreover, the time course of PGE1-induced osteoblast
      proliferation and mineralization suggests that experimental use for 4-8 weeks may
      benefit conditions such as ununited fractures.

PMID- 9025850
TI  - Acute and chronic human adenovirus pneumonia: cellular and extracellular matrix
      components.
AB  - We present a comparative histopathological study of both acute and chronic human
      adenovirus pneumonia, with reference to the cellular and extracellular matrix
      components. Seventeen lungs from autopsied patients whose ages ranged from 2 to
      60 months were studied. Adenovirus types 1, 2, 3, 5, and 7 were isolated from 15
      patients with acute lung disease, and types 2 and 7 were isolated from the other
      two patients with chronic pulmonary illness. The results indicated the occurrence
      of two basic patterns of adenovirus interstitial pneumonia (1) classic pattern
      (acute), characterized by necrosis and degeneration and many type II pneumocytes
      with intranuclear inclusion bodies, which were positive for adenovirus DNA by in
      situ hybridization, and (2) proliferative or proliferative-productive pattern
      (chronic), which presented with diffuse pulmonary fibrosis and the interstitial
      proliferation of fibroblast-like cells, compatible with myofibroblasts (positive
      for vimentin and alpha smooth muscle actin), and increase in collagen types I and
      III, elastic fibers, and proteoglycans. Alveolar collapse appears to be an
      important pathogenetic mechanism in the development of this pattern.

PMID- 9025852
TI  - Pathophysiology versus probability.

PMID- 9025851
TI  - Hypoplastic left heart syndrome in the second trimester.
AB  - Hypoplastic left heart syndrome is a relatively common congenital anomaly with a
      high mortality even after palliative postnatal surgery. The case presented had a
      normal cardiac cavity and great artery dimensions at 19 weeks of gestation but
      bright left ventricular myocardial echoes, impaired left ventricular shortening,
      and no detectable forward flow in the left ventricular outflow tract. Autopsy
      showed left ventricular subendocardial calcification. This demonstrates a likely
      early stage in the evolution of hypoplastic left heart syndrome, which has a
      variable time course. The abnormal left ventricular myocardial performance
      associated with low left ventricular output results in a failure of growth of the
      left heart rather than there being a primary failure of embryogenesis.

PMID- 9025853
TI  - Ependymomas in children express the multidrug resistance gene:
      immunohistochemical and molecular biologic study.
AB  - In view of the poor response of ependymomas to chemotherapy, it may be
      hypothesized that these tumors have intrinsic drug resistance to some
      chemotherapeutic agents. The expression of drug resistance may be specific to a
      single agent or may involve multiple drugs. Among several mechanisms of drug
      resistance, P-glycoprotein (Pgp) has been the subject of considerable attention
      in clinical practice. In order to assess the possible participation of Pgp in the
      chemotherapeutic resistance of ependymomas, 42 biopsy specimens from 35 patients
      with ependymoma seen at our institutions were studied by immunohistochemistry
      with two monoclonal antibodies: C219 (Signet) and UIC-2 (Dr. Roninson's gift). In
      addition, four cases were studied by polymerase chain reaction after reverse
      transcription to detect transcripts of Pgp. Our results showed that in 35 samples
      there was a positive reaction for Pgp with both antibodies; two biopsy samples
      were positive only with C219 and three others with UIC-2; the remaining two
      samples were negative with both antibodies. Of the four cases studied by RT-PCR,
      three showed MDR1 transcripts. These results support our hypothesis of Pgp
      mediated intrinsic multidrug resistance in these tumors.

PMID- 9025854
TI  - Tissue iron storage patterns in fetal hydrops associated with congestive heart
      failure.
AB  - To learn whether fetal congestive heart failure causes a characteristic tissue
      iron storage pattern, we selected 15 neonatal autopsy cases of hydrops fetalis in
      which both the clinical and gross autopsy findings suggested intrauterine
      congestive heart failure. The latter appeared to be due to functional causes in
      10 (3 nonhemolytic anemia, 4 cardiac dysrhythmia, 3 dilated cardiomyopathy) and
      was associated with cardiac malformation in 5. We graded the amount of
      hepatocellular siderosis, reticuloendothelial siderosis, and renal tubular
      siderosis in Perls-stained microscopic sections of liver, spleen, and kidney and
      compared the iron storage pattern with that in 15 normally developed neonatal
      autopsy controls (4 preterm, 11 term) and a further 7 with hemolytic anemia (5
      alpha-thalassemia, 2 parvovirus B19 infection). Liver cell siderosis was absent
      in the three cases with nonhemolytic anemia. It was increased in 11 of the
      remaining 12 cases, as in hemolytic anemia controls. Among the five cardiac
      malformation cases, three had proximal renal tubular siderosis (as in hemolytic
      anemia controls) attributed to turbulent blood flow through the heart. Among the
      five, hydrops appeared to be due to prenatal closure of the foramen ovale in one
      and to prenatal constriction of the ductus arteriosus in another. In one of the
      five, and despite complex malformation of the heart, hydrops appeared to be due
      to complete heart block. We concluded that, although clinical information and
      morphologic assessment of the heart were basic to identifying a cardiac cause of
      fetal hydrops, histologic assessment of the pattern of iron storage helped
      confirm the pathologic diagnosis. Analysis of the pathologic findings led to a
      scheme for categorizing cardiogenic fetal hydrops.

PMID- 9025855
TI  - Functional significance of dystrophin-positive fibers in Duchenne and Becker
      muscular dystrophy.
AB  - In this study, the ratios of dystrophin-positive (+), partially deficient (+/-),
      and deficient (-) fibers were investigated immunohistochemically in 28 Duchenne
      muscular dystrophy (DMD) and 4 Becker muscular dystrophy (BMD) patients using Dys
      I (midrod), Dys II (COOH-terminal), and Dys III (NH2-terminal) antibodies. In the
      biopsies of DMD patients, Dys II was negative in all cases; the mean ratio of Dys
      I (+) fibers was 0.05%, Dys I (+/-) 1.02%, Dys III (+) 0.27%, and Dys III (+/-)
      0.75%. There was no correlation between these (+) or (+/-) fibers and the
      severity of clinical or laboratory findings. In BMD patients, it was shown that
      amino and carboxyl terminals of dystrophin could be affected in addition to the
      midportion.

PMID- 9025857
TI  - Glycogen levels in human term placental disks, umbilical cords, and membranes.
AB  - Glycogen in the placenta and its appendages is important for fetal well-being.
      The precise location of the glycogen stores, however, is unknown. This study was
      initiated to quantitate glycogen levels at well-defined sampling sites in more
      than 641 samples from 10 uncomplicated pregnancies and to correlate these
      glycogen levels with clinical and morphological variables. By biochemical assay,
      glycogen levels were greatest in the midumbilical cord section (29.08 +/- 1.18
      mg/g dry wt) and lowest in the amnionic membrane (2.31 +/- 0.08 mg/g dry wt).
      Within the placental disk, parenchymal glycogen levels were greatest near the
      cord insertion (9.31 +/- 2.68 mg/g dry wt) and lowest at the periphery (5.71 +/-
      1.14 mg/g dry wt). The midumbilical cord glycogen level showed strong direct
      correlations (P < .001) with birth weight, umbilical cord weight, and total
      calculated umbilical cord glycogen and somewhat lower but significant (P < .037)
      direct correlations with the calculated mean umbilical cord glycogen level, total
      calculated placental glycogen content, and placental weight. The glycogen level
      in the middisk parenchymal section from the fetal surface correlated directly
      with gestational age. Periodic acid-Schiff stains showed that magenta glycogen
      granules were most abundant in the cytoplasm of the vascular smooth muscle cells.
      These data show significant variations in glycogen levels among sampling sites.
      Definition of the precise sampling site is important for clinicopathologic
      studies of placental glycogen and for interstudy correlations.

PMID- 9025856
TI  - Inguinal herniation with glial implants: possible complication of
      ventriculoperitoneal shunting.
AB  - The standard treatment of hydrocephalus is the insertion of a valve-regulated
      ventriculoperitoneal (VP) shunt, which may result in the development or clinical
      worsening of an inguinal hernia or hydrocele. A review of the British Columbia's
      Children's Hospital experience with VP shunt insertion (1983-1994) identified 304
      patients who underwent VP shunt placement, 31 of whom subsequently required
      herniorrhaphy, 5 suffering recurrences. Two cases exhibited areas of glial
      differentiation (diffusely scattered in one sac from a bilateral repair, focally
      present in the second unilateral hernia repair) displaying cytoplasmic staining
      with glial fibrillary acidic protein and S100. At time of surgical repair of case
      1 (bilateral hernia repair), the tip of the VP shunt was detected within the
      hernia sac exhibiting glial differentiation; no glial tissue was identified in
      the sac from the other side. We conclude that inguinal herniation is a common
      complication of VP shunt insertion, and the identification of glial tissue within
      such an inguinal hernia is a rarer complication, possibly occurring when the
      shunt tip lies in close proximity to the hernial mesothelial tissue.

PMID- 9025858
TI  - Malignant ectomesenchymoma in childhood.
AB  - Five childhood malignant ectomesenchymomas are reported from three centers in
      three countries. The children were all younger than 3 years (four less than 12
      months), four were boys, and four tumors were sited in the pelvis or external
      genitalia. All tumors had distinctive light microscopic features of
      rhabdomyosarcoma and three also demonstrated small numbers of included neuronal
      cells. Immunohistochemical studies and transmission electron microscopy revealed
      the additional presence of neurogenic components in the remaining two patients.
      An additional epithelial component was found by immunohistochemistry in one
      tumor, which suggests a pluripotential origin that still requires karyotypic
      investigation. Aggressive chemotherapy and adequate surgical excision have thus
      far been effective in providing disease-free follow-up for periods of 7 to 50
      months. It is implied that because the biological behavior and morphology closely
      resemble those of rhabdomyosarcoma and because the neurogenic component is often
      inconspicuous, many malignant ectomesenchymomas may be misdiagnosed as
      rhabdomyosarcomas.

PMID- 9025860
TI  - Extralobar sequestration and type II congenital cystic adenomatoid malformation
      in an infant with congenital diaphragmatic hernia.
AB  - This case report describes an infra-diaphragmatic sequestrated type II congenital
      cystic adenomatoid malformation (CCAM) containing striated muscle fibers in the
      stroma occurring in association with an extra-lobar sequestration (ELS) and a
      congenital diaphragmatic hernia in a female neonate. The classification and
      pathogenesis of CCAM and ELS are reviewed and the relationships between these
      lesions discussed.

PMID- 9025861
TI  - Fatal Bordetella pertussis infection: report of two cases with novel pathologic
      findings.
AB  - We report two infants less than 2 months of age who died of Bordetella pertussis
      infection: one of primary B. pertussis infection and the other of secondary
      bronchopneumonia. We describe histopathologic findings in the lung, including
      transmission and immunoelectron microscopy, studies showing close association
      between B. pertussis organisms and ciliated cells. A novel finding in both cases
      was striking dilatation and inspissation of proteinaceous material in pancreatic
      ducts, reminiscent of changes described in cystic fibrosis. The possible
      mechanism for these changes may be related to cellular and molecular actions of
      pertussis toxin-a powerful inhibitor of G proteins and adenyl cyclase important
      in cellular signal transduction.

PMID- 9025859
TI  - Liver disease in polyglandular autoimmune disease type one: clinicopathologic
      study of three patients and review of the literature.
AB  - We report the findings from liver biopsies of three patients with polyglandular
      autoimmune disease type 1. The livers in two patients had histologic features of
      chronic hepatitis that eventuated in bridging fibrosis and cirrhosis over a
      period of several years. Nonspecific lobular and portal tract inflammation was
      present in the liver biopsy of the third patient. Although these patients did not
      have liver-specific autoantibodies, the liver disease in polyglandular autoimmune
      disease type 1 possibly represents an expression of autoimmune hepatitis.

PMID- 9025862
TI  - Primary acute torsion of the vermiform appendix.
AB  - A case of primary acute appendiceal torsion in a 6-year-old boy with symptoms
      suggestive of acute appendicitis is presented. The appendix was abnormally long,
      measuring 13.5 cm in length. Although appendicitis is the most common intra
      abdominal surgical emergency, there are few descriptions of primary acute
      appendiceal torsion, a rare cause of an acute abdomen. A review of the English
      language literature disclosed 19 reports, including the present, with 11
      pediatric cases. The site of torsion occurs most frequently 1 cm or more from the
      appendiceal base. Rotation varies from 270 degrees to 1080 degrees with a mean of
      580 degrees. The direction of the rotation is more frequently anticlockwise.
      Appendix is most commonly described as lying free or pelvic. In children the mean
      age is 9.1 years, the range 3-16 years, and the male-to-female ratio 4.5:1.

PMID- 9025863
TI  - Nonteratoid medulloepithelioma of the retina with electron microscopic and
      immunohistochemical characterization.
AB  - Medulloepitheliomas are rare intraocular tumors, predominant in children, and
      originate mainly from undifferentiated nonpigmented epithelium of the ciliary
      body. These tumors rarely involve the optic nerve or the retina. They are
      classified as nonteratoid and teratoid types; the latter contains heterologous
      tissues. The teratoid variant of medulloepitheliomas involving the optic nerve or
      the retina is reported in four patients only. We describe the first case of a
      benign nonteratoid medulloepithelioma of the retina in a 3 1/2-year-old girl with
      immunohistochemical and electron microscopic characterization.

PMID- 9025864
TI  - Fetal rhabdomyoma: two instances of recurrence.
AB  - A congenital fetal rhabdomyoma was removed from the neck of a male infant on the
      second day of life. The lesion recurred 10 years later with histological features
      suggestive of increased differentiation and no evidence of malignant
      transformation. An unrelated patient of 3 years suffered from a recurrent fetal
      rhabdomyoma 4 months after the initial resection. The possibility of early or
      late recurrence must be considered when a diagnosis of fetal-type rhabdomyoma is
      made.

PMID- 9025865
TI  - Chronic fibrosing pancreatitis in childhood: report of a case and literature
      review.
AB  - Chronic fibrosing pancreatitis in childhood is an uncommon condition of unknown
      etiology with a variety of clinical presentations, histopathologic features, and
      outcomes. The diagnosis is one of exclusion (of hereditary or secondary
      pancreatitis), which should include histological assessment. The histological
      features of this condition have been described, to our knowledge, in nine
      published cases. We report a case in a 13-year-old male, who presented with
      obstructive jaundice and subsequently had evidence of endocrine and exocrine
      pancreatic insufficiency, despite a surgical decompression of the pancreatic
      biliary duct system.

PMID- 9025866
TI  - Sudden death beyond SIDS.

PMID- 9025867
TI  - Nephrogenic rest and mesoblastic nephroma.

PMID- 9025868
TI  - Pediatric phlebotomy.

PMID- 9025869
TI  - Acquired spinal cord injury in human fetuses with myelomeningocele.
AB  - Experimental studies have shown that there is a potential to attempt in utero
      repair of myelomeningocele in human fetuses. To provide a better understanding of
      the pathology of these lesions we prospectively studied eight stillborn human
      fetuses with myelomeningocele autopsied at The Johns Hopkins Hospital. The intact
      vertebral column with surrounding structures was removed, processed as a single
      block, and prepared as serial histologic sections. Study of the slides showed in
      all cases that in the center of the myelomeningocele the vertebral arch was open,
      the arrangement of meninges was such that the dura mater was open and in
      continuity with the deep layers of the dermis, and the pia mater was open and in
      continuity with a layer consisting of the superficial dermis and the epidermis.
      These meningeal relationships created an abnormally configured arachnoid space
      containing cerebrospinal fluid ventral to the spinal cord, which rested on the
      open pia mater and was exposed on the dorsal aspect of the sac. At the level of
      the myelomeningocele the naked cord had undergone varying degrees of injury up to
      complete loss of neural tissue. Where ventral remnants of the cord remained it
      was evident that a large degree of normal development of the cord had occurred.
      In most instances it appeared that the injury or destruction of the dorsal spinal
      cord was recent and consistent with occurrence during delivery. The results of
      this study support the concept that in utero surgery could preserve and protect
      the exposed spinal cord in a myelomeningocele of a human fetus and thus could
      reduce the severity of the neurologic deficit at birth.

PMID- 9025870
TI  - The cytology of cerebrospinal fluid associated with neonatal intraventricular
      hemorrhage.
AB  - We describe the morphologic features seen in cytocentrifuge preparations of
      cerebrospinal fluid (CSF) from neonates with intraventricular hemorrhage (IVH).
      These CSF specimens from lumbar punctures or ventricular taps often contain
      degenerated red blood cells with blebs and buds, forming microspherocytes
      resembling budding yeast or cocci. Hemosiderin-laden macrophages and foamy
      histiocytes occur in early specimens and persist through multiple specimens.
      Hematoidin, foreign body giant cells, and CSF eosinophilia are later findings.
      Brain tissue fragments are frequently seen at the time of ventricular shunt
      placement. These cytocentrifuge specimens are essentially cytology specimens and
      in children should be reviewed by a qualified pathologist to interpret the
      findings in a clinically relevant manner.

PMID- 9025871
TI  - Tumorlike clusters of immature cells in cerebrospinal fluid of infants.
AB  - Cerebrospinal fluid (CSF) samples from four infants 3 days to 4 months of age
      with a history of prematurity or birth trauma were found to contain clusters of
      immature cells. These cells were arranged in groups or syncytia, sometimes with
      nuclear molding, and were cytologically characterized by scant basophilic
      cytoplasm, nuclei with fine nuclear chromatin, and small nucleoli. The picture
      simulated the appearance of metastatic tumor admixed with hemosiderin-laden
      macrophages, erythrocytes, and leukocytes. Because of the low numbers of cells or
      aggregates present in CSF samples and the relatively small quantity of CSF
      obtained, immunohistochemical and flow cytometric evaluations were not performed.
      Prior studies have designated these immature cells as undifferentiated
      leptomeningeal cells or cells from the subependymal germinal matrix and have
      associated their presence with intraventricular hemorrhage (IVH) in premature
      newborns. Three of our patients had a history of prematurity; the fourth patient
      suffered a traumatic birth but was not premature. In long-term follow-up, the
      patients have not shown progression of neurologic deficits or evidence of
      malignancy. Thus, it is important to recognize that in infants with a history of
      IVH, subarachnoid hemorrhage, or ventricular drainage devices, the presence of
      tumorlike clumps of cells associated with hemosiderin-laden macrophages most
      likely does not represent metastatic tumor.

PMID- 9025872
TI  - Clinical significance of increasing histologic severity of acute inflammation in
      the fetal membranes and umbilical cord.
AB  - The purpose of this study was to determine the importance of varying histologic
      stages of inflammation in the placental membranes and cord. Acute inflammation
      was histologically staged in fetal membranes and umbilical cord sections from
      2899 placentas received from consecutive singleton deliveries. Then clinical data
      were collected for a subset of randomly selected placentas with stage 1 through
      stage 4 membrane inflammation (n = 212) and without significant inflammation
      (stage 0, n = 216). Statistical analyses revealed that increasing stage of
      membrane inflammation was associated with an increasing rate of funisitis,
      perinatal death, and preterm birth (P < .05). Inflammation permeating the entire
      trophoblastic layer of the chorion (stage 1) was associated with clinical
      symptoms of intrauterine infection and thus was an important pathologic finding.
      Acute necrotizing chorioamnionitis was very strongly associated with perinatal
      death and preterm birth. Acute funisitis was a more specific but less sensitive
      marker for perinatal complications than inflammation in the membranes. With
      increasing stage of funisitis, there was an increased incidence of clinical
      symptoms of intrauterine infection, preterm birth, and perinatal death. Almost
      three-fourths of the cases with histologic evidence of membrane inflammation were
      clinically silent. In conclusion, increasing histologic stages of inflammation of
      the membranes and cord are associated with an increased rate of perinatal
      morbidity and mortality. Stage I membrane inflammation provides a clinically
      acceptable minimum threshold for the reporting of pathologic changes.

PMID- 9025873
TI  - Growth fraction determination in pulmonary hypoplasia using Ki-67 (MIB-1)
      antibody.
AB  - Pulmonary hypoplasia (PH) is a developmental abnormality that is typically
      assessed using lung/body weight ratios, radial alveolar counts, or lung volume
      measurements. Although it is often assumed that PH results from failure of growth
      and development, analysis of the proliferative index in PH has not been
      extensively described. We examined the lungs of 12 fetuses and newborn infants
      with pulmonary hypoplasia and those of 8 gestational age-matched controls using
      Ki-67 immunohistochemistry. Formalin-fixed, paraffin-embedded tissues were
      utilized. Growth fractions (GFs) were determined for peripheral lung parenchyma
      and bronchioles. The ratio of GFs for parenchyma and bronchioles was compared.
      There was no significant difference in the GF ratios obtained between control and
      hypoplastic lungs when gestational age was < 24 weeks. However, for gestational
      age > 24 weeks the GF ratio of mean values for controls was approximately four
      times the ratio of the mean values for the hypoplastic lungs. GF did not vary
      according to the presumed cause of PH, and at gestational ages < 24 weeks rates
      were the same as or greater than those of controls. These findings suggest that
      proliferative potential exists at < 24 weeks and that the growth of the lung
      parenchyma in relation to the conducting airways is significantly reduced or
      ceases after this point in gestation. Clinical interventions at or before 24
      weeks of gestation might result in improved survival of infants with a propensity
      for pulmonary hypoplasia.

PMID- 9025874
TI  - Perianal abscess and fistula in ano in infancy and childhood: a
      clinicopathological study.
AB  - This is a retrospective study of 78 children with perianal abscess and/or fistula
      in ano presenting during a 6 1/2-year period. Sixty-five were males and 13
      females. Their ages at presentation ranged from 22 days to 18 years (median 1.7
      year), and the majority of males were below 2 years of age. The 13 females all
      presented with perianal abscess, the majority of which grew Staphylococcus aureus
      (69.2%). On follow-up, none of them developed fistula in ano. Twenty-two of the
      65 males (33.8%) presented initially with fistula in ano. The remaining 43
      presented with perianal abscess. Four of them were found to have fistula in ano
      at the time of incision and drainage and on follow-up, and 14 others developed
      fistula in ano. Of the 40 cases of fistula in ano, all were males; 25 were on the
      right side and 9 on the left side, 5 had bilateral fistula in ano, and 1 had two
      fistulas on the left side at 3 and 5 o'clock positions. Gut-derived organisms
      were isolated from 88.4% of the males with perianal abscess. There appears to be
      a causal relationship between perianal abscess and fistula in ano.

PMID- 9025875
TI  - Proliferative activity of adrenal glands with adrenocortical cytomegaly measured
      by MIB-1 labeling index.
AB  - To investigate the proliferative activity of cytomegalic cells in the fetal
      adrenal cortex, we studied adrenal glands with cytomegaly by immunohistochemistry
      using the nuclear proliferation maker MIB-1. The percentage of positively stained
      nuclei was quantified using the SAMBA 4000 image analysis system. Only one case
      showed occasional positively stained cytomegalic cell nuclei. The permanent
      cortices showed proliferative activity that decreased with increasing gestational
      age. No proliferative activity was seen in normal fetal cortices except in one
      case that received corticosteroid therapy and had a maternal history of diabetes.
      The near absence of proliferative activity of the cytomegalic cells supports the
      previously proposed theory of cellular exhaustion following hyperactivity. The
      high proliferative activity in the fetal cortex of the infant receiving
      corticosteroid therapy may provide insight into the stimulus causing the
      hypermetabolic state.

PMID- 9025876
TI  - All-trans-retinoic acid-induced growth suppression of blastemal Wilms' tumor.
AB  - All-trans-retinoic acid (RA) has been used to suppress growth of malignant cells
      and induce epithelial differentiation. We investigated whether RA had a similar
      effect on Wilms' tumor, a childhood tumor of the kidney that arises from the
      undifferentiated metanephric blastema. W13 cells, a cell line derived from a
      blastemal Wilms' tumor, were exposed to RA (10(-9)-10(-5) M) and its effects on
      cell proliferation, gene expression, and differentiation were examined. Treatment
      of W13 cells with RA resulted in a dose-dependent suppression of growth. Changes
      in expression of selected genes were determined by Northern analysis. After 24 h,
      there was a marked dose-dependent down-regulation of N-myc mRNA as well as up
      regulation of insulin-like growth factor-II (IGF-II) mRNA. [125I]IGF-II ligand
      blotting of conditioned medium from RA-treated cultures revealed a dramatic
      alteration in the pattern of expression of insulin-like growth factor binding
      proteins (IGFBPs). Examination of RA-treated W13 cultures by light and electron
      microscopy did not reveal appreciable morphological changes. We conclude that RA
      inhibits growth and alters gene expression of W13 cells without inducing
      epithelial differentiation. The modulation of expression of IGF-II, IGFBP, and N
      myc may play a role in RA-induced growth suppression of Wilms' tumor cells.

PMID- 9025877
TI  - Tumors of childhood in Ibadan, Nigeria (1973-1990).
AB  - Childhood neoplasms provide a fertile field for epidemiological research and
      afford a unique opportunity for studying possible mechanisms of carcinogenesis.
      The present study reviews 1881 malignant childhood neoplasms in children less
      than 15 years of age seen in the University College Hospital, Ibadan during an 18
      year period. The male-to-female ratio was 1.4:1 and modal age of occurrence was
      10 years. The most common childhood neoplasms were lymphomas (45.4%),
      retinoblastomas (9.7%), and malignant renal neoplasms (8.5%). Burkitt's lymphoma
      constituted 92% of all lymphomas and 37% of all childhood tumors. Comparison of
      two clinicopathological studies of childhood cancer in Ibadan between 1960-1972
      and 1973-1990 revealed a dramatic upsurge in the relative frequencies of
      intracranial neoplasms, leukemias, renal neoplasms, and retinoblastomas, with a
      decline in the relative frequencies of bone neoplasms and Burkitt's lymphoma
      during the latter period. Whether these changes reflect actual changes in the
      distribution of childhood cancer in the local population will require further
      study.

PMID- 9025878
TI  - Pluripotential melanoblastoma, a unifying concept on malignancies arising in
      congenital melanocytic nevi: report of two cases.
AB  - Congenital melanocytic nevi are benign lesions present at birth and considered to
      be caused by a maldevelopment of the neural crest. The malignant potential of the
      congenital melanocytic nevi have been extensively addressed by several authors,
      and malignant melanoma is the most frequent neoplasm arising in these lesions.
      The present report describes two patients with congenital melanocytic nevi in
      which malignant melanoma with undifferentiated areas showing rhabdomyoblastic
      differentiation developed. The findings suggest that these mixed neoplasms may be
      recapitulating the differentiation potential of the ectomesenchyme-neural crest
      cells. We advocate the term "melanoblastoma" when referring to them.

PMID- 9025879
TI  - Extradural myxopapillary ependymoma: report of two cases and review of the
      literature.
AB  - The cauda equina is the most frequent location for ependymomas, particularly the
      myxopapillary variant, which generally arises from the filum terminale. These
      tumors have a characteristic histopathologic pattern and are usually easily
      recognized. The occurrence of these tumors in an extradural, sacrococcygeal, or
      subcutaneous location may prove challenging, particularly in the absence of any
      obvious central nervous system connection. We describe two such extradural cases,
      one with multiple regional and distant metastases and the other with multiple
      recurrences. The origin of these tumors from subcutaneous sacrococcygeal
      ependymal rests is postulated on the basis of earlier reports. Clinical and
      histopathological features are described and a review of the literature is
      presented.

PMID- 9025880
TI  - Retinoic acid embryopathy: case report and review of literature.
AB  - Isotretinoin use as a treatment for acne has increased tremendously and, with it,
      the problems of associated birth defects. We feel that pathologists should be
      familiar with isotretinoin embryopathy and its pathogenesis in order to assist in
      differentiating this syndrome from other genetic syndromes that involve branchial
      arch defects, such as DiGeorge syndrome or velocardiofacial syndrome. Although
      selected autopsy findings have been presented in epidemiologic reports, to our
      knowledge a detailed autopsy report has not been published. We therefore wish to
      present a complete case study of isotretinoin embryopathy that illustrates the
      pathologic diagnostic criteria and correlates these with the clinical findings.
      Although the syndrome's major features are explained by the drug's effect on
      neural crest cells, it has been postulated that isotretinoin also affects other
      cells in the central nervous system. Our current case supports this theory and
      shows that these changes in the nervous system may present significant functional
      impairment, while not presenting visible anatomic changes on either imaging
      studies or routine histologic examinations.

PMID- 9025881
TI  - Coexistence of cerebellar primitive neuroectodermal tumor and cerebellar
      dysplasia: case report.
AB  - It has been speculated that the cerebellar primitive neuroectodermal tumor (PNET)
      in part recapitulates stages in the maturation of normal human neuroblasts. One
      theory suggests that these tumors may arise from "primitive cells" or "remnants"
      of the external granular layer of the cerebellum, which forms a subpial,
      proliferative zone that gives rise to neurons of the internal granular layer and
      stellate and basket cells. In the present report, the coexistence of marked
      cerebellar cortical disorganization and cerebellar PNET is described in a 1-year
      old boy. The abnormal dysplastic cortex was in close proximity as well as
      contiguous to the tumor. Although minor degrees of cerebellar dysplasia may be
      found incidentally, the coexistence of a severe malformative process contiguous
      to cerebellar PNET merits the consideration of a possible pathogenetic
      association between aberrant neuronal migration or maturation and the development
      of PNET in this patient.

PMID- 9025882
TI  - Propylthiouracil-induced fulminant hepatitis: case report and review of the
      literature.
AB  - Propylthiouracil (PTU), a thyroid hormone inhibitor, is widely used for the
      treatment of hyperthyroidism. Rarely, the drug has been associated with severe
      hepatotoxicity. We present the case of a 13-year-old girl who developed jaundice
      and profound liver dysfunction with rapid progression to metabolic encephalopathy
      while receiving PTU therapy. She died despite extensive therapeutic measures
      including orthotopic liver transplantation. Her rapid clinical course and fatal
      outcome show that in spite of regular monitoring, severe, rare, rapidly occurring
      complications of PTU therapy may still occur.

PMID- 9025883
TI  - A teratoid Wilms' tumor with raised serum alpha-fetoprotein level.
AB  - Tumor markers are used to diagnose certain cancers and can be useful in
      monitoring the response to treatment. We describe a renal tumor with the features
      of a teratoid nephroblastoma associated with a raised serum level of alpha
      fetoprotein (AFP). The serum AFP remained high during chemotherapy but returned
      to normal after nephrectomy. AFP was demonstrated by immunohistochemistry in
      cysts lined by enteric-type epithelium within the tumor. Cytogenetic examination
      of the tumor showed a clone of cells with trisomy 8. Raised serum AFP has not
      previously been described in teratoid Wilms' tumor.

PMID- 9025884
TI  - Laboratory utilization--lessons from China?

PMID- 9025885
TI  - Clonal analysis of sacrococcygeal "teratomas".
AB  - Congenital masses of the sacrococcygeal region commonly contain multiple tissues
      and have variously been subclassified as neoplasms or congenital hamartomas based
      on clinicopathological and embryological observations. We have used a polymerase
      chain reaction-based assay for nonrandom X chromosome inactivation to infer the
      clonality of three cogenital sacrococcygeal tumors previously diagnosed as
      teratomas. One solid immature teratoma was monoclonal, and a predominantly cystic
      histologically mature mass was polyclonal. A third immature teratoma was
      noninformative because of baseline asymmetry of polyclonal tissue X inactivation.
      We confirm that immature teratomas at this site appear to be monoclonal neoplasms
      and suggest that at least some histologically mature "teratomas" are more
      appropriately classified as hamartomas.

PMID- 9025886
TI  - Is there transplacental transfer of asbestos? A study of 40 stillborn infants.
AB  - An autopsy study was conducted to investigate whether there is transplacental
      transfer of asbestos in humans. The asbestos burden of lung, liver, skeletal
      muscle, and placenta digests of 40 stillborn infants was determined using a
      bleach digestion method. The fibers detected in the tissue digests were
      characterized as to the type of asbestos, using electron microscopy, energy
      dispersive x-ray analysis, and selected-area diffraction analysis. Placental
      digests of 45 full-term, liveborn infants were similarly processed as controls.
      Low levels of small, thin, uncoated asbestos fibers were detected in the
      placentas and organs of 37.5% of the stillborn infants (15 of 40). The fiber
      sizes ranged from 0.05 to 5.0 microns in length and 0.03 to 0.3 micron in width,
      with a mean length of 1.15 microns and a mean width of 0.069 micron. Maximum
      numbers of fibers were found in the lungs (mean 235,400 fibers/g; n = 10),
      followed by liver (mean 212,833 fibers/g; n = 6), placenta (mean 164,500
      fibers/g; n = 4), and skeletal muscle (80,000 fibers/g; n = 1). The fibers were
      detected at all stages of gestation and showed no association with gestational
      age. A significant association was found between fiber presence and working
      mothers, and positive but nonsignificant associations were found with maternal
      history of drug abuse, previous abortions, and fetal maceration. No association
      was found between premature rupture of membranes and fiber presence. No fibers
      were detected in the 45 placentas of the liveborn control infants. There was a
      highly significant difference in the asbestos fiber counts of the placentas of
      the stillborn and liveborn infants (P < .001). Our studies demonstrate the
      presence of short and thin asbestos fibers in stillborn infants and their
      positive association with working mothers.

PMID- 9025887
TI  - Cellular composition of the angiofibromas in tuberous sclerosis.
AB  - The angiofibroma of tuberous sclerosis is associated with a proliferation of
      dermal spindle cells that have been considered to be fibroblasts on the basis of
      a variety of techniques, although some cells have a glial appearance. This study
      of six angiofibromas demonstrated an increase in S100-positive, peanut agglutinin
      negative spindle cells in the dermis in addition to increased numbers of
      epidermal melanocytes. The second major spindle cell population in the dermis
      proved to be dermal dendrocytes based on their expression of factor XIIIa. The
      number of these cells decreases in older patients, in whom the lesions were
      generally less cellular and more fibrotic. The angiofibroma of tuberous sclerosis
      is a hamartoma involving increased numbers of dermal dendrocytes,
      neurosustentacular cells, blood vessels, and melanocytes, in addition to
      collagen.

PMID- 9025888
TI  - Reference values for singleton and twin placental weights.
AB  - The largest series of normal singleton placental weights was collected in the
      Collaborative Perinatal Study between the years 1959 and 1966 but values for
      normal twin placental weights were not published. In our study we examined 787
      singleton and 514 twin normal placentas. Placentas with associated conditions
      known to affect the weights of placentas were excluded. After establishing the
      normal values for singleton and twin placental weights, we concluded that weight
      gain of twin placentas appears to accelerate between 24 and 36 weeks but reaches
      a plateau after 37 weeks, whereas singleton placentas appear to gain weight more
      uniformly throughout gestation. The mean values of twin placental weights for
      each gestational age are less than double those of singleton placental weights
      for the same duration of gestation. Our singleton and twin placentas are heavier
      than those from previously published data and may reflect a generational or
      nutritional change over the 30 years since the original numbers were compiled.

PMID- 9025889
TI  - Axial skeleton and pituitary gland in human fetuses with spina bifida and cranial
      encephalocele.
AB  - The purpose of this study was to investigate the axial skeleton and the pituitary
      gland in fetuses with spina bifida or cranial encephalocele in order to elucidate
      the pathogenesis of the conditions. The findings were related to former
      investigations performed on normal fetuses and on fetuses with anencephaly and
      rachischisis. Eight human fetuses from spontaneous or therapeutic abortions, 11
      28 weeks of gestational age, were investigated. Radiographs were taken of the
      axial skeleton and histological investigation, including immunohistochemical
      marking for thyroid-stimulating hormone was performed on tissue blocks of the
      cranial base, including the sella turcica and the pituitary gland. Radiography
      revealed only minor malformations in the axial skeleton and not in all cases. The
      types of malformations resembled those seen in anencephaly and rachischisis.
      Histological investigations revealed severe malformations in the sella turcica
      region in spina bifida and minor ones in cranial encephalocele. Pharyngeally
      located adenopituitary gland tissue occurred in all fetuses. Anencephaly and
      cranial encephalocele seemingly are conditions resulting from different
      expressivity of the same multifactorial process of maldevelopment involving
      mesoderm (skeleton), neurectoderm (spinal cord and brain), and surface ectoderm
      (adenopituitary gland tissue). It is suggested that the molecular biological
      signaling between the notochord, the scleroderm, and the surface ectoderm is
      disturbed in spina bifida and cranial encephalocele.

PMID- 9025891
TI  - Placental examination in intrauterine coinfection with herpes simplex virus and
      cytomegalovirus.
AB  - Intrauterine coinfections have rarely been reported. However, pregnancies exposed
      to multiple sexually transmitted infectious agents and drugs are likely to occur
      with increasing frequency and lead to complex pathology in the newborn. Often it
      will be difficult to establish a diagnosis, above all when this has to be done
      retrospectively. A premature (34 weeks) newborn presented with a complex clinical
      picture after exposure to multiple infectious and noninfectious teratogens during
      gestation. Immunocytochemical staining of the placental membranes and parenchyma
      suggested intrauterine coinfection by herpes simplex virus (HSV) type 2 and
      cytomegalovirus. This case illustrates the importance of careful placental
      investigation with modern techniques for the diagnosis of intrauterine HSV
      infection and coinfections.

PMID- 9025890
TI  - Gastrin-releasing peptide in hypoplastic lungs.
AB  - The relative abundance of pulmonary neuroendocrine cells synthesizing gastrin
      releasing peptide (GRP) was estimated for normal fetal lungs and hypoplastic
      lungs. Percentage of bronchiolar epithelial area staining positively with anti
      GRP antiserum was computed for each case using a SAMBA 4000 image analyzer. The
      majority of hypoplastic lungs (10 of 12 cases) showed markedly diminished GRP
      immunoreactivity, which appeared to vary with etiology. Six cases of pulmonary
      hypoplasia associated with renal anomalies, three cases associated with hydrops,
      and one case of diaphragmatic hernia showed an average fivefold reduction in
      percentage of GRP immunostaining. A case of hypoplasia associated with Werdnig
      Hoffmann disease had GRP immunoreactivity similar to that of controls, and GRP
      expression was markedly elevated (fivefold) in a case of hypoplasia with
      omphalocele.

PMID- 9025892
TI  - Spectrum of glomerulocystic kidneys: a case report and review of the literature.
AB  - An 8-year-old boy developed end-stage renal disease 7 years after the in utero
      diagnosis of bilateral cystic kidneys. There was no history of cystic renal
      disease in the family. Initial ultrasonographic screening of the parents failed
      to reveal cysts in the kidneys. Pathological evaluation of the kidney biopsy
      findings was consistent with the glomerulocystic kidney disease. He had bilateral
      nephrectomies in preparation for a living related renal transplant at 7 years of
      age. At that time, a repeated renal ultrasound examination of the mother showed
      bilateral cystic kidneys. Pathological evaluation of the nephrectomy specimens
      confirmed the diagnosis of autosomal dominant polycystic kidney disease. In this
      report, a discussion of the differential diagnosis of glomerular cysts and the
      relationship of glomerulocystic kidney disease and autosomal dominant polycystic
      kidney disease is provided.

PMID- 9025893
TI  - Clear cell rhabdomyosarcoma.
AB  - A clear cell rhabdomyosarcoma was studied by light microscopy, histochemistry,
      immunohistochemistry, and electron microscopy. It was a large, painful left
      parapharyngeal mass in a 10-year-old boy with intracranial extension and cervical
      metastatic enlarged lymph nodes. Tumor tissue was macroscopically grayish. At
      microscopic examination, the architecture was diffuse and focally alveolar. Tumor
      cells were of three types. Most cells were large, round or polygonal, with
      abundant clear vacuolated cytoplasm. Fibrils were sometimes found to be present
      around the nucleus. Nuclei often had irregular outlines and multiple nucleoli.
      Mitotic activity was high. Some round or elongated cells had eosinophilic
      fibrillar cytoplasm and were found to have a few double striations. A few cells
      were round and medium sized with a high nucleocytoplasmic ratio. Periodic acid
      Schiff stain demonstrated huge amounts of intracytoplasmic glycogen in clear
      cells. Tumor cells showed positive immunostaining for muscle markers (desmin,
      muscle actins, dystrophin). Electron microscopy showed large lakes of glycogen,
      lipid droplets, and striated muscle features.

PMID- 9025894
TI  - Multinodular hyperplastic pannephric nephroblastomatosis with tubular
      differentiation: a new morphologic variant.
AB  - We report a case of bilateral nephromegaly detected prenatally with
      oligohydramnios. Delivered at 35 weeks, this black male infant rapidly developed
      renal failure, requiring dialysis. He lived 3 1/2 months. The kidneys were three
      times normal size and diffusely multinodular, with hypoplastic calyces, no
      corticomedullary demarcation, and no pyramids. Histologically, they revealed
      hyperplastic embryonal rests composed of tubules and ducts with prominent
      branching. The nodular rests were intermixed with areas of mature parenchyma,
      which showed prominent oxalosis. By flow cytometry, rests were diploid, with an S
      phase fraction of 25.9%. The proliferation of embryonal collecting system analogs
      is attributed to excessively rapid and prolonged branching of the ureteric bud,
      dating from the fourth gestational month or earlier. This unique case may
      represent a new morphologic variant of universal nephroblastomatosis.

PMID- 9025895
TI  - Salivary gland anlage tumor of the nasopharynx: a clinicopathologic and
      immunohistochemical study of three cases.
AB  - The histologic and immunohistochemical features of three congenital pedunculated
      nasopharyngeal midline masses are reported. The follow-up in all cases was
      uneventful. The tumors were characterized by solid and cystic squamous nests and
      ductlike structures focally continuous with the surface squamous mucosa of the
      tumor. Most of epithelial structures coalesced with densely cellular stroma-like
      nodules. Immunoperoxidase staining showed the presence of epithelial markers in
      both spindle cells and epithelial structures. Spindle cells were also reactive to
      vimentin and smooth muscle actin, revealing their myoepithelial phenotype. Based
      on these observations, a diagnosis of salivary gland anlage tumor, also called
      congenital pleomorphic adenoma of the nasopharynx, was made. The similarity of
      these tumors' architecture and cellular composition to the normally developing
      salivary gland has led to the hypothesis of a tumorlike, hamartomatous lesion
      developing in a site in which minor salivary gland tissue occurs. This report
      reviews 12 identified cases of this tumor, of which all but one (in which the
      patient died of sepsis) had a favorable outcome. In an infant with respiratory
      distress and/or feeding difficulties, these tumors must be differentiated from
      other midline masses such as encephaloceles and teratomas. They appear curable by
      surgical exeresis only.

PMID- 9025896
TI  - Idiopathic arterial calcification and unexpected infant death.
AB  - Two infants who died unexpectedly and who were found at autopsy to have
      idiopathic arterial calcification are presented. The first infant died within
      hours of the sudden onset of shortness of breath. The second infant died suddenly
      and unexpectedly in hospital where he was being treated for presumed sepsis and
      cardiac failure. Neither infant had significant past or family histories. Autopsy
      examination in both infants demonstrated widespread fibrointimal proliferation of
      elastic and muscular arteries with characteristic calcification of the internal
      elastic laminae. Kidneys and parathyroid glands were normal. Death in case 1 was
      attributed to extensive myocardial ischemic damage with right coronary artery
      ostial stenosis due to idiopathic arterial calcification. Death in case 2 was
      attributed to saddle pulmonary thromboembolism arising from a right atrial
      thrombus associated with cardiac failure secondary to idiopathic arterial
      calcification. These cases demonstrate the variable presentations, causes of
      death, and autopsy findings that may occur in this uncommon condition.

PMID- 9025897
TI  - Recurrent villitis of bacterial etiology.
AB  - Recurrent placental villitis is an uncommon clinicopathologic entity associated
      with a very high perinatal mortality rate. While most cases are idiopathic, other
      cases may have a treatable infectious cause. Here, a mother with recurrent fetal
      losses, each showing chronic villitis associated with rod shaped bacilli as
      demonstrated by Steiner stain, is presented. The key feature separating this and
      other similar cases from idiopathic villitis is a pleomorphic inflammatory
      infiltrate including lymphocytes, macrophages, eosinophils, plasma cells, and
      neutrophils.

PMID- 9025898
TI  - Dedifferentiated cystic nephroma with malignant mesenchymoma as the
      dedifferentiated component.
AB  - Cystic tumors of the kidney are uncommon and usually do not have solid areas. We
      report a predominantly cystic renal tumor with solid anaplastic component showing
      rhabdomyoblastic and cartilaginous differentiation in a 26-month-old girl.
      Terminology and pathogenesis of tumor progression are discussed along with a
      review of reports of tumors associated with cystic nephroma.

PMID- 9025899
TI  - Renal pathology in WAGR syndrome.
AB  - The Wilms' tumor-aniridia-genital anomalies-mental retardation (WAGR) syndrome is
      associated with an increased risk for developing Wilms' tumor. A right
      nephrectomy was performed following the diagnosis of Wilms' tumor in a 2-year-old
      girl with WAGR syndrome and chromosome 11, del 11p13. Pathologic examination
      revealed intralobar nephrogenic rests and a peripelvic multicystic mass, sharply
      delineated from the adjacent typical intralobar nephrogenic rests and renal
      parenchyma, which may represent a cystic Wilms' tumor (cystic partially
      differentiated nephroblastoma). We studied the expression of the H19 gene by in
      situ hybridization performed on paraffin sections of the kidney. H19 is an
      imprinted maternally-expressed gene that is not translated to protein and
      functions as a regulatory RNA molecule. It is tightly linked with the paternally
      imprinted gene of insulin-like growth factor 2. While IGF2 presumably plays a
      role in tumorigenesis of Wilms' tumor, H19 is not expressed in the majority of
      Wilms' tumors. The expression of H19 in the intralobar nephrogenic rests was
      found to be prominent in the component of the blastema and markedly reduced with
      differentiation to tubular structures similar to the fetal kidney. The
      differential diagnosis of hyperplastic intralobar nephrogenic rests from a small
      Wilms' tumor arising in intralobar nephrogenic rests is difficult. Complete
      understanding of the chain of molecular events occurring in the evolution of
      Wilms' tumors may lead to the development of tumor markers to be used on paraffin
      sections and so help in the differential diagnosis of hyperplasia versus
      malignant transformation.

PMID- 9025900
TI  - The quadrupole ion trap mass spectrometer--a small solution to a big challenge.

PMID- 9025901
TI  - Peptide substrates suitable for assaying glycogen synthase kinase-3 in crude cell
      extracts.
AB  - In this study we describe the characterization and use of new peptide substrates
      for assaying glycogen synthase kinase-3 (GSK-3) which are based on the sequence
      around the single GSK-3 phosphorylation site in the translation factor eIF2B. The
      new peptides offer important advantages over previous substrates, which were
      based on the sequence around the multiple GSK-3 phosphorylation sites in glycogen
      synthase (GS), for the assay of GSK-3 in cell extracts. In particular, decreases
      in GSK-3 activity following, e.g., insulin treatment, are partially or completely
      masked when the GS-based peptides are used but are readily measured using the
      new, eIF2B-based, peptides. The new peptides, unlike those based on GS, are
      therefore suitable for the assay of changes in GSK-3 activity in cell extracts
      without the need for prior immunoprecipitation or ion-exchange chromatography.

PMID- 9025902
TI  - Measure of transient transfection efficiency using beta-galactosidase protein.
AB  - Although the control elements which regulate the transcriptional activity of
      promoter sequences are largely determined by the use of reporter plasmids in
      transient transfection analyses, controlling variability in these experiments can
      often be a vexing problem. Problems arise when the promoter of the internal
      control plasmid, used to correct for transfection efficiency, either affects test
      promoter strength or is itself regulated by trans-acting factors or inducing
      agents used to study the test promoter. Here we report the use of beta
      galactosidase protein as an unbiased standard of transfection efficiency. beta
      Galactosidase protein is readily internalized by adherent cell lines when
      incorporated into a calcium phosphate precipitate; significant enzyme activity
      can be recovered up to 72 h after transfection. Use of beta-galactosidase protein
      as a control obviates the concerns associated with promoter-dependent reporter
      plasmids as controls.

PMID- 9025903
TI  - Sensitive reverse staining of bacterial lipopolysaccharides on polyacrylamide
      gels by using zinc and imidazole salts.
AB  - We present a new method for visualizing bacterial lipopolysaccharides
      (LPS)/lipooligosaccharides (LOS) electrophoresed in sodium dodecyl sulfate
      polyacrylamide gels. After electrophoresis, gels are washed in boiling water to
      appreciably remove remaining electrophoresis reagents, then incubated in 10 mM
      zinc sulfate for 15 min, and subsequently immersed in 0.2 M imidazole for 3 min.
      As a result, zinc salts precipitate all over the gel surface except in the zones
      occupied by LPS/LOS, which appear as transparent, colorless bands. Gels can be
      stored in distilled water for weeks without loss of the negative image. The
      sensitivity of this stain is similar to that of silver. We believe that zinc
      imidazole may be a suitable nontoxic alternative to silver in the rapid analysis
      of LPS/LOS by polyacrylamide gel electrophoresis.

PMID- 9025904
TI  - Immunofluorescence assay for the quantitative and qualitative evaluation of
      intracellular interleukin-8 in microtiter plates.
AB  - In order to monitor the effects of drugs on interleukin-8 (IL-8) production by
      cells, a microtiter plate assay that determines four parameters simultaneously
      was established (i) levels of secreted IL-8 (supernatant ELISA), (ii) levels of
      intracellular IL-8 (cell ELISA), (iii) intracellular localization (fluorescence
      microscopy), and (iv) the amount of cellular protein (colorimetric assay). The
      quantitative and qualitative determination of intracellular IL-8 was achieved by
      immunofluorescence using the ELF-detection system (Molecular Probes, Eugene, OR),
      which is approximately 10 times more sensitive than conventional
      immunofluorescence detection systems. Thus, a 32x objective magnification
      (without immersion oil) is sufficient to precisely assess the subcellular
      localization of IL-8. Experiments were carried out with human umbilical vein
      endothelial cells. Drugs interfering with transcription or translation and
      inhibitors of protein kinase C inhibited both production and secretion of IL-8.
      Brefeldin A (BFA), colchicine, and the HMGCoA-reductase inhibitor fluvastatin
      disrupted the characteristic Golgi localization of IL-8, but only BFA inhibited
      its secretion. This assay can therefore be used to distinguish drugs that inhibit
      both IL-8 synthesis and secretion from those that inhibit IL-8 secretion only. It
      can easily be adapted to other cellular proteins for which a sensitive detection
      method is required.

PMID- 9025905
TI  - A rapid fluorescence bioassay for the determination of selenium on agar plates.
AB  - The essential trace element selenium (Se) is involved in the form of
      selenocysteine at the active site of several prokaryotic and eukaryotic proteins
      called selenoproteins. These proteins have recently attracted attention
      particularly in relation to their application to human health and new
      characteristics of the genetic code. We have recently described a selenium
      bioassay based on a recombinant DNA construct in which the expression of the lac'
      Z gene in Escherichia coli is proportionally and specifically driven by UGA
      directed selenocysteine incorporation. Here we have further developed this
      bioassay for more rapid and sensitive detection and measurement of selenium that
      permits screening of the selenium status on agar plates. Again, the inclusion of
      selenium into the lac'Z-fusion product is reflected by the level of beta
      galactosidase activity, which in turn is reflected by the intensity of
      fluorescence on agar plates. This fluorescing agent is a 4-methylumbelliferyl
      moiety which is released through the cleavage by the enzyme of 4
      methylumbelliferyl-beta-D-galactoside. The intensity of the fluorescence is
      easily detected by uv irradiation and photographed by polaroid or video cameras.

PMID- 9025906
TI  - Continuous enzymatic assay for phosphorylase kinase in a monocascade enzyme
      system.
AB  - A turbidimetric method for continuous monitoring of the enzymatic reaction
      catalyzed by rabbit skeletal muscle phosphorylase kinase has been developed. The
      reaction mixture contained the substrates of glycogen phosphorylase a, i.e.,
      glycogen and glucose 1-phosphate (or P(i)), in addition to the usual components
      of the kinase reaction. The kinetics of the cascade enzyme system were followed
      by the change in glycogen concentration over time, as measured by the absorbance
      of the reaction medium at 360 nm. The reliability of this turbidimetric method
      for measuring phosphorylase kinase activity was proven by comparison with a
      commonly used radiochemical assay. We present here a newly developed method for
      calculating the initial rate of phosphorylase kinase reaction in our conjugated
      system. We demonstrate that our procedure is applicable for investigating the
      hysteretic properties of phosphorylase kinase.

PMID- 9025909
TI  - Cationic liposomes enhanced firefly bioluminescent assay of adenosine 5'
      triphosphate disodium salt.
AB  - Cationic liposomes containing stearylamine enhanced the intensity of maximum
      light emission from the firefly luciferin-luciferase reaction with ATP in the
      range of 1.0 pM up to 5.5 nM. In contrast, the bioluminescent intensities in the
      presence of anionic and zwitterionic liposomes were about the same as those in
      water alone. The detection limit for ATP in the presence of cationic liposomes
      was 1.0 pM in aqueous ATP standard solutions. The sensitivity for ATP was
      improved by a factor of five times compared to that in water alone. The method
      was applied to the determination of ATP in Escherichia coli extracts. The
      sensitivity threshold was presumed to be 340 cells ml-1.

PMID- 9025908
TI  - Detection and characterization of phospholipase D by flow injection analysis.
AB  - A precisely working automated system for the investigation of phospholipases D
      (PLDs, EC 3.1.4.4) from plant and microbial sources with flow injection analysis
      (FIA) has been developed. The two versions of the FIA setup described are based
      on the oxidation of choline liberated from phosphatidylcholine by PLD action and
      catalyzed by choline oxidase and the chemiluminescence detection of hydrogen
      peroxide produced by this reaction. The correlation between this
      chemiluminescence signal and the PLD activity was linear in the range between 1
      and 100 mU/ml PLD. The sampling frequency was 12 samples per hour. This method
      was used to compare three different PLDs from cabbage and microbial sources with
      respect to their pH optima, temperature stability, effectors, and v/[S]
      characteristics.

PMID- 9025907
TI  - Quantitation of ERCC-2 gene expression in human tumor cell lines by reverse
      transcription-polymerase chain reaction in comparison to northern blot analysis.
AB  - Excision repair cross-complementing rodent repair deficiency genes (ERCC) are
      human genes implicated in nucleotide excision repair. ERCC-2 has been implicated
      in the repair of DNA damaged by chemotherapeutic agents, and may thus play an
      important role in anticancer drug resistance. ERCC-2 gene expression is low in
      primary tumor samples rendering it difficult to quantitate. We have developed a
      semiquantitative method to measure ERCC-2 gene expression utilizing reverse
      transcription-polymerase chain reaction (RT-PCR). Total RNA extracted from
      established human tumor cell lines was reverse-transcribed to obtain cDNA.
      Serially diluted reference ERCC-2 DNA fragment was amplified by PCR to obtain a
      617-bp fragment. A standard curve was then created using densitometry readings of
      the 617-bp bands on agarose gel. A fixed amount of sample cDNA from each cell
      line was amplified at the same time and the resultant PCR product was read by
      densitometer. Using the standard curve, ERCC-2 gene expression in a given amount
      of total RNA was quantitated and normalized to beta-actin expression. There was
      minimal variation in three repeated experiments with PCR amplification. ERCC-2
      gene expression determined by this semiquantitative PCR was also correlated to
      ERCC-2 quantitation by Northern blot analysis, with a significant concordance (r
      = 0.912, P = 0.0002). We also successfully applied this sensitive method to
      quantify five clinical glioma samples.

PMID- 9025910
TI  - Synthetic polynucleotide templates for characterizing sequence-selective small
      molecule/nucleic acid interactions.
AB  - A synthetic polynucleotide sequence was developed and cloned to serve as a target
      in footprinting and other assays designed to characterize the sequence-selective
      binding of drugs and other small molecules to various forms of nucleic acids. The
      target sequence comprehensively represents all base quartet recognition sites in
      a minimal length sequence. Minimal length target sequences were found to be 144
      nt long. One such target sequence was divided into two parts. One strand of each
      part was chemically synthesized and the complementary strands were generated
      using a DNA polymerase. Double-stranded sequences were then cloned into pGEM
      3Zf(+/-) vectors (Promega, Inc.). The cloned target sequence can be used directly
      in double-stranded DNA form. Alternatively, features of the plasmid vector allow
      expression of the target sequences as single-stranded DNA or RNA or as RNA/DNA or
      RNA/RNA duplexes. These cloned target sequences designed for high information
      content overcome limitations to the use of natural DNA sequences for footprinting
      and related experiments arising from the unequal representation of base quartets
      and the potential for secondary structure formation in single-stranded forms.

PMID- 9025911
TI  - Identification and measurement of oxindole (2-indolinone) in the mammalian brain
      and other rat organs.
AB  - Oxindole, a putative tryptophan metabolite able to cause profound sedation when
      administered in relatively low doses to mammals, has been identified and measured
      in the brains of mice, rats, and guinea pigs using HPLC and GC/MS with a
      quadrupole ion trap and a collision-induced dissociation mass spectrometer. The
      identification and measurement of the compound required a protein precipitation
      step with HClO4, extraction into chloroform, an HPLC separation on a reverse
      phase column, and detection by UV or coulometry. The definitive identification of
      the oxindole peak was obtained with a Saturn 4D GC/MS quadrupole ion trap
      operated under GC/MS, GC/MS/MS, and GC/MS/MS/MS modes. The HPLC methods we used
      had a low interassay variability, easily allowing the identification and
      measurement of the compound in 1 g of tissue. The oxindole concentrations in rat
      brain, blood, liver, and kidney were each approximately 100 pmol/g wt.
      Interestingly, the content of oxindole in the guinea pig brain was found to be
      significantly lower than that in the mouse and rat brains, possibly reflecting a
      lower dietary intake of tryptophan in the guinea pigs.

PMID- 9025912
TI  - Synthesis and luminescence spectral characterization of long-lifetime lipid metal
      ligand probes.
AB  - We synthesized phospholipid analogues of phosphatidyl ethanolamine which contains
      a ruthenium metal-ligand complex (MLC) covalently bound to the amino group. Two
      analogues were synthesized, containing either one (Ru-PE) or two (Ru-PE2) lipid
      molecules covalently linked to the MLC by the amino group of the lipid. These MLC
      lipid probes display intensity decay times from 682 to 357 ns, depending on
      temperature. Importantly, the luminescence MLC groups display polarized emission,
      enabling their use for studies of membrane dynamics. The long intensity decay
      times allowed measurement of the overall rotation correlation time of lipid
      vesicles to several microseconds. The spectral properties of the model membranes
      containing Ru-PE or Ru-PE2 were independent of the probe-to-lipid molar ratio
      from 1:20 to 1:100, suggesting minimal tendency for probe-probe interactions.
      These MLC-lipid probes can be expected to have numerous applications in studies
      of membrane dynamics on the microsecond timescale.

PMID- 9025913
TI  - Fluorescence properties of pteridine nucleoside analogs as monomers and
      incorporated into oligonucleotides.
AB  - Eighteen fluorescent pteridine-based nucleoside analogs have been prepared that
      are suitable for synthesis as phosphormidites and site-specific incorporation
      into oligonucleotides. Their quantum yields ranged from < or = 0.03 to 0.88. The
      maximum excitation and emission wavelenghts of seven selected probes with quantum
      yields > 0.15 ranged from 334 to 358 and 400 to 444 nm, respectively.
      Fluorescence decay curves of the seven probes were biexponential, and the mean
      intensity-weighted lifetimes ranged from 0.87 to 6.54 ns. Incorporation of probes
      4 and 17 (3-methylisoxanthopterin and 6-methylisoxanthopterin) into
      oligonucleotides significantly quenched their fluorescence signal, and the degree
      of quench correlated with the number and proximity of purines in the
      oligonucleotide. Incorporation also resulted in a shift in absorbance-, emission
      , and decay-associated spectra for 6-methylisoxanthopterin. An increase in the
      complexity of the decay curve and a decrease in the mean lifetime occurred for
      both probes. Formation of double-stranded oligonucleotides did not substantially
      increase the degree of quenching but generally increased the complexity of decay
      curves and decreased the mean lifetimes. Melting temperature, Tm, depression
      equivalent to that of a single base pair mismatch was observed in 3
      methylisoxanthopterin-containing double-stranded oligonucleotides, while the Tm
      of 6-methylisoxanthopterin-containing double-stranded oligonucleotides were
      unperturbed, e.g., equivalent to unlabeled double-stranded oligonucleotides. This
      new class of fluorophore yields promising probes for the study of protein/DNA
      interactions.

PMID- 9025915
TI  - Coupled enzymatic assay for the determination of sucrose.
AB  - An enzymatic spectrophotometric assay for the determination of sucrose in
      unextracted samples of serum and urine was developed. The method entailed the
      coupling of invertase-catalyzed sucrose hydrolysis with a fructose dehydrogenase
      catalyzed oxidation of the liberated fructose. The latter reaction generated
      reducing equivalents that were transferred to a tetrazolium salt with a
      concomitant increase in absorbance at 570 nm. The assay, which was carried out in
      microtiter plates, had a minimum detectable sucrose concentration of 0.03
      mmol/liter and run-to-run and within-run coefficients of variation of 7.5 and
      6.7%, respectively, and showed a good correlation with urine sucrose
      determination by GLC (r = 0.92). The assay range of 0.03-2.10 mmol/liter is
      suitable for the quantitation of serum sucrose following iv administration and
      for the quantitation of urine sucrose at basal levels and following the
      consumption of an oral test dose of sucrose. This method was used to analyze
      urine samples from a group of human subjects who consumed 20 g of sucrose for the
      assessment of gastroduodenal permeability. This convenient assay provides for the
      rapid and specific estimation of sucrose and has the potential to be used in a
      variety of manual, semiautomated, or automated formats.

PMID- 9025914
TI  - Quantification of cell-matrix and cell-cell adhesion using horseradish
      peroxidase.
AB  - A simple, universal, and rapid enzymatic method for the quantitative
      determination of cell adhesion in 96-well cell culture plates has been
      established. The assay is based on cellular steady-state endocytosis, which is
      used to label cells with horseradish peroxidase (HRP) prior to adhesion.
      Subsequently, attached cells can be detected by a simple enzymatic reaction, in
      which the accumulated HRP catalyzes dye formation from a colorless hydrogen
      donor, e.g., o-phenylenediamine, in the presence of hydrogen peroxide. As
      demonstrated with different cell lines and test systems, the method can be used
      to quantify cell-matrix as well as cell-cell interactions and allows a very
      sensitive quantification of adherent cells. The HRP label is nontoxic and does
      not affect the adhesion properties of tested cell lines; the quantity of dye
      formed is proportional to the number of adherent cells. Furthermore, the assay
      represents an alternative method to isotopic cell labeling, e.g., with 51Cr,
      which is usually used for quantifying cell-cell interactions.

PMID- 9025916
TI  - Quantitation of 5-lipoxygenase products by electrospray mass spectrometry: effect
      of ethanol on zymosan-stimulated production of 5-lipoxygenase products by human
      neutrophils.
AB  - A reverse-phase-HPLC/tandem mass spectrometric method (LC/MS/MS) was developed
      for the quantitation of leukotriene B4 (LTB4), the 5-lipoxygenase product, 5
      hydroxyeicosatetraenoic acid (5-HETE), as well as the omega-oxidation metabolites
      of LTB4, 20-hydroxy-LTB4, and 20-carboxy-LTB4. Electrospray-generated carboxylate
      anions were collisionally activated and decomposed to specific and abundant
      product ions and multiple reaction monitoring was used to analyze LTB4 (m/z 335-
      >195), 20-hydroxy-LTB4 (m/z 351-->195), 20-carboxy-LTB4 (m/z 365-->195), and 5
      HETE (m/z 319-->115). A linear correlation was observed in comparison of results
      obtained from quantitation by LC/MS/MS with quantitation by gas chromatography/MS
      of the pentafluorobenzyl ester/trimethylsilyl ether derivative of LTB4 produced
      during opsonized zymosan stimulation of human neutrophils. Detection limits at
      the low picogram level were obtained for all metabolites. This method was applied
      to the quantitation of 5-lipoxygenase products produced from zymosan-stimulated
      human neutrophils in the presence of ethanol. At physiologically relevant
      concentrations of ethanol, production of all 5-lipoxygenase products generated by
      stimulated neutrophils was markedly attenuated.

PMID- 9025917
TI  - Improvement of the Eakins and Brown method for measuring 59Fe and 55Fe in blood
      and other iron-containing materials by liquid scintillation counting and sample
      preparation using microwave digestion and ion-exchange column purification of
      iron.
AB  - The simultaneous measurement of 59Fe and 55Fe in whole blood by liquid
      scintillation counting by the Eakins and Brown (EB) method is extensively used in
      iron absorption studies. The EB method requires many steps which increase the
      chances of error and decrease its sensitivity. We describe two modifications to
      the above method consisting of microwave digestion and column purification of
      iron. This "New Method" (NM) is simpler and more precise, and sensitive than the
      EB method. Counting efficiencies with the NM are similar for 59Fe (75%) as with
      the EB method but are better for 55Fe (29% for NM vs 22%), and cross counting
      from 59Fe into the 55Fe window is lower with the NM (3.7-4.5%) than with the EB
      method (10-12%). For the NM, recoveries of radioactive blood samples, in relation
      to processed standards ranged from 100 to 103% for 59Fe and 101 to 113% for 55Fe.
      For the EB method, recoveries ranged from 94 to 99% for 59Fe and from 88 to 93%
      for 55Fe. Even with very low counts, average intrarun CV with the NM was lower
      than 5.4% for either isotope, while it was as high as 10.0% for 55Fe with the EB
      method.

PMID- 9025918
TI  - BIA/MS: interfacing biomolecular interaction analysis with mass spectrometry.
AB  - Biomolecular interaction analysis (BIA) which utilizes surface plasmon resonance
      (SPR) detection of affinity-captured analytes has been interfaced with matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI).
      Femtomole quantities of a peptide, myotoxin a, were detected by direct MALDI
      analysis of sensor chips used during BIA of a polyclonal anti-myotoxin a
      IgG/myotoxin a system. Further, different interactive surfaces (flow cells)
      present on a single biosensor were targeted individually for mass spectrometric
      analysis. System compatibility of the combined approach was demonstrated with
      sensitivities, detection limits, and analytical performances comparable to those
      intrinsic to the individual analyses. The combined approach unites the real-time
      capabilities of SPR-based BIA with the qualitative specificity of mass
      spectrometry.

PMID- 9025919
TI  - Studies of protein interactions by biosensor technology: an alternative approach
      to the analysis of sensorgrams deviating from pseudo-first-order kinetic
      behavior.
AB  - A procedure for evaluating the thermodynamic equilibrium constant by kinetic
      analysis of sensorgrams which deviate from the pseudo-first-order kinetic
      behavior predicted for 1:1 interactions between ligate and affinity sites on the
      sensor surface is described. This analysis employs quantitative expressions that
      are used in conventional kinetic characterization of protein interactions by
      biosensor technology, but with the equilibrium sensorgram response fixed at a
      predetermined magnitude. Simulated sensorgrams for situations in which the
      aberrant kinetic behavior reflects (i) heterogeneity of affinity sites and (ii)
      isomerization of the complex between ligate and affinity sites are used to
      explore the feasibility of the approach. Its application is then illustrated with
      BIAcore studies of the interaction between the Fab fragment of an anti-paraquat
      monoclonal antibody and immobilized antigen in the form of a paraquat analog
      attached covalently to the sensor surface. Studies with an extremely high degree
      of antigen substitution on the sensor surface yielded sensorgrams that deviated
      markedly from pseudo-first-order kinetic behavior. However, they yielded the same
      binding constant (3 x 10(6) M-1) as the value deduced by conventional analysis of
      sensorgrams that conformed with pseudo-first-order kinetics because of a much
      lower concentration of immobilized antigen on the sensor surface. Such identity
      of binding constants eliminates heterogeneity of immobilized paraquat sites as
      the likely source of the aberrant kinetic behavior.

PMID- 9025920
TI  - The use of osazones as matrices for the matrix-assisted laser
      desorption/ionization mass spectrometry of carbohydrates.
AB  - Fifteen sugar osazones were synthesized and evaluated for their use as matrix
      assisted laser desorption/ ionization matrices. Various carbohydrate samples were
      analyzed, indicating that D- or L-arabinosazone, prepared from D- or L-arabinose
      and phenylhydrazine, gave the overall best performance. The arabinosazones
      facilitated superior analyses in providing a highly uniform distribution of
      sample molecules within the matrix microcrystals, and a possibility of using low
      laser energy for irradiation, leading to high spectral resolution and low matrix
      background. The arabinosazones with a moderate content of sodium ions promoted
      specific fragmentation for certain carbohydrates tested. The 50 fmol amounts of
      maltohexaose and maltoheptaose (present in 0.1 microliter of sample/matrix
      solution) were detected at a signal-to-background ratio of 3:1.

PMID- 9025921
TI  - Use of a resonant mirror biosensor to characterize the interaction of
      carboxypeptidase A with an elicited monoclonal antibody.
AB  - The binding of apocarboxypeptidase A to an immobilized form of its elicited
      monoclonal antibody has been used to explore the potential of a biosensor
      instrument (IAsys) based on resonant mirror technology for the quantitative
      characterization of antibody-antigen interactions. Advantage has been taken of
      the stirred cuvette design of the IAsys instrument to develop a stepwise
      titration procedure for thermodynamic characterization of the interaction, an
      association equilibrium constant of 3.3 (+/-0.9) x 10(7) M-1 having been obtained
      under the conditions studied (0.1 M Tris/HCl-0.5 M NaCl, pH 7.5, 21 degrees C).
      In a test of the feasibility of subjecting the time course of biosensor response
      to conventional pseudo-first-order kinetic analysis, nonconformity of results
      with such description was encountered at high and low concentrations of
      apocarboxypeptidase A. Whereas the deviations from Langmuirian kinetic behavior
      at high antigen concentrations undoubtedly stem from the same sources as those
      already encountered in studies with the BIA-core biosensor instrument, the
      deviations at the other concentration extreme occur in a range in which the
      assumed constancy of free antigen concentration in the liquid phase is becoming a
      poor approximation. An alternative approach in such circumstances has been tested
      in which prior thermodynamic characterization is a prerequisite for rate constant
      evaluation by means of a second-order kinetic analysis. Finally, the effect of
      soluble anticarboxypeptidase A on the pseudo-first-order kinetics of the
      biosensor response has been used to illustrate a simple kinetic procedure for
      evaluating the affinity constant for the antibody-antigen interaction in
      solution, a value of 1.9 (+/-0.2) x 10(8) M-1 being obtained by such means.

PMID- 9025922
TI  - Quantitative reverse zymography: analysis of picogram amounts of
      metalloproteinase inhibitors using gelatinase A and B reverse zymograms.
AB  - Matrix metalloproteinases are a growing family of neutral pH optima, zinc atom
      dependent endopeptidases that collectively degrade all components of the
      extracellular matrix. This family of related proteases is further defined by
      their inhibition of protease activity by a class of low-molecular-weight
      endogenous inhibitors known as tissue inhibitors of metalloproteinases or TIMPs.
      Reverse zymography is an electrophoretic technique used to identify TIMP
      inhibitory activity within acrylamide gels. Previous methods have generally used
      biochemically complex sources of proteolytic activity (such as cell culture
      conditioned media) copolymerized with a proteinase substrate in the gel to
      identify the zones of inhibited proteolysis. We describe a novel system for
      reverse zymography using purified recombinant human gelatinase A or gelatinase B
      in place of conditioned media. These reverse zymograms using recombinant
      gelatinase have sensitivities for TIMPs that are favorable in comparison to
      immunoblotting techniques but have the benefit of visualizing multiple inhibitors
      simultaneously. We have developed and characterized these methods for the
      evaluation of inhibitors and have shown them to be highly sensitive, convenient,
      and reproducible. Both systems detect TIMPs 1, 2, and 3 simultaneously, but with
      differential sensitivities for TIMPs 1 and 2. Using gelatinase A the system can
      detect as little as 1 pg of rTIMP-2, but the limit of detection for rTIMP-1 is 40
      pg. Gelatinase B shows less differential activity in that the limits of detection
      are 60 and 40 pg for TIMP-2 and TIMP-1, respectively. We demonstrate how these
      varied sensitivities of the gelatinases for the TIMPs can contribute to potential
      pitfalls in systems using uncharacterized reagents (i.e., conditioned media).

PMID- 9025923
TI  - A procedure for cloning genes from genomic DNA using weakly hybridizing
      heterologous probes and a polymerase chain reaction-based screening: cloning of
      the chickpea urate oxidase gene.

PMID- 9025924
TI  - Preparation of monoclonal antibody against plant extracellular glycoprotein with
      deglycosylated peptide as antigen.

PMID- 9025925
TI  - Quantitation of mouse and rat beta-actin mRNA by competitive polymerase chain
      reaction using capillary electrophoresis.

PMID- 9025926
TI  - Spectrophotometric determination of iodixanol in subcellular fractions of
      mammalian cells.

PMID- 9025927
TI  - Activity staining of protein inhibitors of proteases on gelatin-containing
      polyacrylamide gel electrophoresis.

PMID- 9025928
TI  - Ultraviolet shadowing as a tool to estimate DNA concentrations in solution.

PMID- 9025929
TI  - Formate dehydrogenase-coupled spectrophotometric assay of peptide deformylase.

PMID- 9025930
TI  - Evidence and prevention of HIV-1 nucleocapsid protein adsorption onto
      fluorescence quartz cells.

PMID- 9025931
TI  - Protease site-restricted selection of phage-displayed peptides on glutathione
      sepharose.

PMID- 9025932
TI  - The detection of chemically initiated cells having the mutation of K-ras gene at
      an early stage of lung carcinogenesis in mice.

PMID- 9025933
TI  - Affinity purification of tagged recombinant proteins using immobilized single
      chain Fv fragments.

PMID- 9025934
TI  - A nonradioactive, allele-specific polymerase chain reaction for reproducible
      detection of rare mutations in large amounts of genomic DNA: application to human
      k-ras.

PMID- 9025936
TI  - Measurement of nitrite and nitrate in biological fluids by gas chromatography
      mass spectrometry and by the Griess assay: problems with the Griess assay-
      solutions by gas chromatography-mass spectrometry.
AB  - Assay methods based on the Griess reaction are frequently used to measure nitrite
      and nitrate in urine, plasma, and other biological fluids. With minor exceptions,
      careful attention has not been paid in extending the Griess assay from aqueous
      solutions to biological fluids, In the present study, parallel measurements of
      nitrite and nitrate were performed in urine, plasma, and aqueous solutions with a
      published batch assay based on the Griess reaction and with gas chromatography
      mass spectrometry (GC-MS). We report here further interferences by free reduced
      thiols, proteins, and other plasma constituents in the Griess assay but not in GC
      MS. The best correlation (r2 = 0.985) between the Griess assay and GC-MS was
      observed for aqueous solutions in the absence of thiols. Unlike GC-MS, the Griess
      assay was not applicable to whole human plasma and urine samples. For the
      measurement of nitrate in diluted human urine samples, reduction by cadmium was
      performed both under acidic (pH 2 or 5) and alkaline (pH 8.8) conditions. The
      mean recovery rate of nitrate from urine samples was quantitative in the GC-MS
      but amounted to only 30-80% in the Griess assay. Measurement of nitrate in human
      urine samples (n = 33) resulted in an excellent correlation between two GC-MS
      techniques (r2 = 0.979) but only in a poor correlation (r2 < 0.64) between the
      Griess assay and GC-MS. Unlike GC-MS, the batch Griess assay is associated with
      many problems in measuring nitrate in biological fluids.

PMID- 9025935
TI  - Recent advances in capillary electrophoresis of DNA fragments and PCR products in
      poly(n-substituted acrylamides).
AB  - In this article, capillary electrophoresis of DNA fragments and polymerase chain
      reaction products in sieving liquid polymers is reviewed. The first part of the
      review is dedicated to the development of N-substituted acrylamides, which in
      general guarantee a greater resistance to hydrolytic attack. Among the various
      monomers developed, an outstanding molecule appears to be N-acryloyl
      aminopropanol (AAP), which combines an extreme resistance to alkaline hydrolysis
      (500 times greater than plain acrylamide) with a substantially higher
      hydrophilicity. Poly(AAP) matrices exhibit a unique behavior in DNA separations,
      especially at high temperatures (60 degrees C), where most other matrices fail.
      In separation of antisense oligonucleotides, isoelectric buffers allow very high
      field strengths (up to 800 V/cm) due to their extremely low conductivity, thus
      permitting separations on the order of a few minutes. Among such buffers,
      histidine (pH = pI = 7.47) and lysine (pH = pI = 9.74) appear to be the best
      ones. Detection of DNA point mutations is accomplished with a peculiar
      nonisocratic capillary zone electrophoresis (CZE), consisting of creating
      temporal thermal gradients, analogous to temperature-programmed gas
      chromatography. A unique approach is described, consisting of creating
      temperature gradients not with external thermostats, but with internal Joule
      effects produced by voltage programming (which results in temperature ramps). The
      review ends with some unique applications of CZE: the possibility of precise gene
      dosage, relying on on-line detection and quantitation of the separated peaks.
      Examples of such gene dosages are given, such as assessment of Down's syndrome
      and determination of homozygous and heterozygous states of RhD blood groups.

PMID- 9025937
TI  - Metal-catalyzed photooxidation of histidine in human growth hormone.
AB  - Reports on nonenzymatic oxidation of human growth hormone (hGH) have been
      previously limited to methionyl residues (Met14 and Met125). We report on the
      oxidation of a histidyl residue in hGH treated with intense light. The
      photooxidation process is predominately site-specific to histidine at position
      21, which forms a cation-binding site along with His18 and Glu174. This site
      binds metal ions and, under intense light, catalyzes the oxidation of His21.
      Products are formed by the addition of one, two, or three atoms of oxygen to the
      histidyl residue.

PMID- 9025938
TI  - Polyacrylamide gel electrophoresis in discontinuous transverse urea-gradient
      gels.
AB  - Polyacrylamide gel electrophoresis in transverse urea-gradient gels is widely
      used for the study of changes in conformation and quaternary structure of
      proteins induced by increasing concentrations of urea. However, possible
      uncertainties regarding the effective concentration of urea at any given point
      across the gel must be considered when this technique is used for quantitative
      purposes. We describe here a simple, practical procedure for preparing urea
      gradient gels discontinuously, by stacking various layers of acrylamide solution
      with increasing urea concentrations. We show that the urea concentration in
      different lanes of discontinuous gradient gels prepared in this way can be
      predetermined accurately enough for quantitative purposes and provide as an
      example the study of the dissociation of thyroglobulin in urea. Various levels of
      resolution can be attained by this technique. The use of discontinuous gradient
      gels may extend the usefulness of urea gel electrophoresis in relation with the
      quantitative aspects of the study of protein conformation.

PMID- 9025939
TI  - A continuous method for measuring calpain activity.
AB  - A simplified methodology for assaying the caseinolysis by calpains was developed.
      This methodology, including the incubation of calpain with casein and direct
      measurement of the absorbance at 500 nm, is based on the turbidity of the
      reaction mixture caused by the aggregation of hydrolysates during the reaction.
      Unlike the typical caseinolysis assay, this novel assay does not need to separate
      the substrate from hydrolysates and can be continuously monitored in visible
      wavelength range. The activity of calpain is expressed by the maximum reaction
      velocity (delta A500/min) at 25 degrees C).

PMID- 9025940
TI  - Maximum entropy, analysis of kinetic processes involving chemical and folding
      unfolding changes in proteins.
AB  - We show that numerical inversion of the Laplace transform by using the maximum
      entropy method can be successfully applied to the analysis of complex kinetic
      processes involving chemical and folding-unfolding changes in proteins. First, we
      present analyses of simulated data which support that: (i) the maximum entropy
      calculation of rate distributions, combined with Monte Carlo analyses of the
      associated uncertainties, yields results consistent with the information actually
      supplied by the data, thus preventing their over-interpretation; (ii) maximum
      entropy analysis may be used to extract discrete rates (corresponding to
      individual exponential contributions), as well as broad rate distributions
      (provided, of course, that the adequate information is supplied by the data). We
      further illustrate the applicability of the maximum entropy analysis with
      experimental data corresponding to two nontrivial model processes: (a) the
      kinetics of chemical modification of sulfhydryl groups in glycogen synthase by
      reaction with Ellman's reagent; (b) the kinetics of folding of ribonuclease a
      under strongly folding conditions, as monitored by fluorescence and optical
      absorption. Finally, we discuss that the maximum entropy approach should be
      particularly useful in studies on protein folding kinetics, which generally
      involve the comparison between several complex kinetic profiles obtained by using
      different physical probes. Thus, protein folding kinetics is usually interpreted
      in terms of kinetic mechanisms involving a comparatively small number of kinetic
      steps between well-defined protein states. According to this picture, rate
      distributions derived from experimental kinetic profiles by maximum entropy
      analysis are expected to show a small number of comparatively narrow peaks, from
      which we can determine, without a priori assumptions, the number of exponential
      contributions required to describe each experimental kinetic profile (the number
      of peaks), together with their amplitudes (from the peak areas), time constant
      values (from the peak positions), and associated Monte Carlo uncertainties. On
      the other hand, recent theoretical studies describe protein folding kinetics in
      terms of the protein energy landscape (the multidimensional surface of energy
      versus conformational degrees of freedom), emphasize the difficulty in defining a
      single reaction coordinate for folding, and point out that individual chains may
      fold by multiple pathways. This indicates that, in some cases at least, folding
      kinetics might have to be described in terms of broad rate distributions (rather
      than in terms of a small number of discrete exponential contributions related to
      kinetic steps between well-defined protein states). We suggest that the maximum
      entropy procedures described in this work may provide a method to detect this
      situation and to derive such broad rate distributions from experimental data.

PMID- 9025941
TI  - An optical submicrometer calcium sensor with conductance sensing capability.
AB  - The identification of chemical species and the measurement of their
      concentrations with high (submicrometer) spatial resolution are of considerable
      importance in cell biology. In this article we report the first successful
      development of a > or = 0.1-micron Ca2+ sensor based on a pulled micropipet,
      filled with a conducting porous sol-gel glass which was doped with the
      fluorescent calcium green 1 Ca2+ indicator. Such sensors are potentially capable
      of measuring Ca2+ concentrations as low as 10(-8) M, in confined volumes, with a
      three-dimensional resolution which exceeds approximately 0.1 micron. A major
      advantage of the sensor is its capability to be integrated into a multifunctional
      probe which will measure chemical analyte concentrations and ion conductance.

PMID- 9025942
TI  - Characteristics of DNA-tagged liposomes allowing their use in capillary
      migration, sandwich-hybridization assays.
AB  - Liposomes that have been labeled externally with a DNA oligomer are used in a
      capillary-migration, sandwich-hybridization assay for specific DNA target
      sequences. The liposomes are used in a DNA detection scheme that produces
      visually observable results in 10 min. The preparation and covalent attachment of
      a thiol-activated 22-base oligomer to the external surface of dye-containing
      liposomes is described, and the specificity of the assay toward perfectly
      complementary target DNA is demonstrated. Several characteristics of DNA-tagged
      liposomes that allow the use of increased stringency during hybridization are
      evaluated. These include the effect of temperature, formamide, and salt
      concentration on both the sandwich-hybridization assay and the liposomes
      themselves. The effects of several components of a common hybridization solution
      are determined with regard to both assay performance and liposome stability.
      Using a solution of 0.02% sodium dodecyl sulfate in 3X standard saline citrate, a
      visual detection limit of 200 amol of target DNA was obtained.

PMID- 9025943
TI  - Trace quantification of the oxidative damage products, meta- and ortho-tyrosine,
      in biological samples by gas chromatography-electron capture negative ionization
      mass spectrometry.
AB  - Oxygen radicals damage biomolecules and may contribute to cellular aging and
      degenerative disease. We describe a sensitive method for the quantification of
      two endogenous biomarkers of oxidative damage: meta-tyrosine (m-Tyr) and ortho
      tyrosine (o-Tyr). The assay can be applied to direct analysis of free amino acids
      or protein-bound amino acids following hydrolysis. The assay involves
      derivatization with pentafluorobenzyl bromide and extraction into n-decane,
      followed by gas chromatography-mass spectrometry. Stable isotope labeled m- and o
      Tyr (2H4) and phenylalanine [i.e., Phe (2H5)] were added as internal standards to
      improve analytical accuracy. Quantification of as little as 50 pg of m- and o-Tyr
      in 100 micrograms protein is possible and the data are expressed as a molar ratio
      of m- and o-Tyr to native Phe. The assay was used to determine the levels of m-
      and o-Tyr in freshly isolated human plasma protein (4.05 +/- 0.67 m-Tyr per 10(4)
      Phe, 0.35 +/- 0.07 o-Tyr per 10(4) Phe). Exposure of human plasma to reactive
      oxygen species significantly increased the levels of m-Tyr (56.4 +/- 1.1 m-Tyr
      per 10(4) Phe, P < 0.0001) and o-Tyr (48.9 +/- 1.3 o-Tyr per 10(4) Phe, P <
      0.0001). The mild hydrolysis and derivatization conditions caused no artifactual
      formation of either m- or o-Tyr.

PMID- 9025944
TI  - 3-(4-Carboxybenzoyl)quinoline-2-carboxaldehyde, a reagent with broad dynamic
      range for the assay of proteins and lipoproteins in solution.
AB  - This paper describes the application of 3-(4-carboxybenzoyl)quinoline-2
      carboxaldehyde (CBQCA), a sensitive fluorogenic reagent for detection of amines,
      to the assay of proteins in solution. The sensitivity and dynamic range of CBQCA
      in the determination of protein concentration is modulated by the number of
      accessible amines present in the protein assayed. Thus, this method bears the
      same limitations as other reagents used in fluorogenic assays based on
      fluorescent amine adducts such as those obtained with fluorescamine or o
      phthaldialdehyde, or of other spectrophotometric methods, where the color
      development is determined by the abundance in the protein of certain amino acids.
      However, in comparison to other fluorescence-based protein detection methods,
      CBQCA has proven to be an extremely sensitive reagent with a very broad,
      essentially linear dynamic range, capable of detecting from 10 ng to 150
      micrograms of protein (in a 100- to 200-microL assay volume). The CBQCA reagent
      also functions well in the presence of substances, such as lipids, known to
      interfere in many other protein determination methods.

PMID- 9025945
TI  - Capillary electrophoresis of carboxylated carbohydrates. III. Selective precolumn
      derivatization of glycosaminoglycan disaccharides with 7-aminonaphthalene-1,3
      disulfonic acid fluorescing tag for ultrasensitive laser-induced fluorescence
      detection.
AB  - Eight different glycosaminoglycan-derived disaccharides were selectively labeled
      via their carboxylic acid group with 7-aminonaphthalene-1,3-disulfonic acid
      (ANDSA) by a condensation reaction between the amino group of ANDSA and the
      carboxylic acid group of the saccharides in the presence of water-soluble
      carbodiimide. This derivatization reaction yielded stable derivatives with
      percentage yields as high as 97%. The ANDSA disaccharide derivatives were readily
      detected by on-column laser induced fluorescence (LIF) with a He-Cd laser at 325
      nm. With LIF, the limit of detection was at the nanomolar level, three orders of
      magnitude lower than the limit of detection of underivatized disaccharides in the
      uv at 231 nm. In addition, due to the presence of two strong sulfonic acid groups
      in the ANDSA tag, the derivatives were readily separated at acidic pH (i.e., pH
      4.0-5.0) using 100 mM sodium acetate buffers as the running electrolytes. The
      addition of polycationic spermine in small amounts to the running electrolytes
      provided different selectivity with baseline resolution in the pH range 6.0-7.0,
      and the excess ANDSA migrated ahead of the ANDSA disaccharides.

PMID- 9025946
TI  - Simultaneous quantitative determination method for sphingolipid metabolites by
      liquid chromatography/ionspray ionization tandem mass spectrometry.
AB  - Sphingolipid metabolites ceramide, sphingomyelin, sphingosine, psycosine,
      sphingosylphosphorylcholine, and dimethylsphingosine were separated and
      simulataneously quantitated by liquid chromatography/ionspray ionization tandem
      mass spectrometry (LC/MS/ MS). The use of glassware throughout minimized losses
      due to adsorption and the pretreatment of this method consisted of simple liquid
      liquid extraction procedure with a mixture of chloroform and methanol. After
      separation on a short C18 silica column eluted in a gradient mode, the
      metabolites were detected by MS/ MS. This assay allows simultaneously
      quantification of these metabolites over a range of at least 0.1 to 100 ng/ 10(6)
      cells. The LC/MS/MS analyses took 10 to 15 min per sample and we could examine up
      to 50 samples per day. We also detected endogenous sphingosine 1-phosphate in HL
      60 cells. The utility of the method was demonstrated by examining changes in
      metabolites levels in HL-60 cells after treatment with sphingomyelinase. It was
      found that sphingomyelinase from Bacillus cereus may have selectivity for acyl
      chain length.

PMID- 9025947
TI  - Identification and minimization of nonideal binding effects in BIAcore analysis:
      ferritin/anti-ferritin Fab' interaction as a model system.
AB  - The interaction of human spleen ferritin with a monoclonal antibody Fab' fragment
      has been studied as a model system for BIAcore analysis. In particular, the
      influence of nonideal binding effects has been examined both experimentally and
      by the theoretical simulation of sensorgram curves. Mass transfer effects were
      found to have a small but significant influence on the observed binding kinetics
      of the ferritin/antiferritin Fab' interaction; however, this nonideal behavior
      could be overcome by systematic manipulation of experimental conditions such as
      the flow rate and the surface density of the immobilized antigen. Because of the
      multivalent nature of ferritin with 12 antiferritin Fab' binding sites per
      molecule, immobilization of the antigen by amine coupling had little effect on
      the majority of free binding sites on the molecule. Consequently, the binding
      data for both ferritin and apoferritin correlated well with an ideal binding
      model which assumes binding homogeneity. On the other hand, when ferritin was
      dissociated to its subunit dimer form (containing one Fab' binding site) prior to
      surface immobilization significant deviation from this model was observed. This
      nonideal behavior was probably due to heterogeneity of the immobilized ferritin
      subunit dimer on the sensor surface, resulting from the nonspecific amine
      coupling procedure.

PMID- 9025948
TI  - Quantitating oligonucleotide affinities for duplex DNA: footprinting vs
      electrophoretic mobility shift assays.
AB  - Determining the affinities of oligonucleotides for duplex DNA is an important
      analytical problem that arises during the design of potential gene repressors
      based on triple helix recognition. Quantitative DNa-seI footprinting assays
      (QDFA) offer a rigorous technique for this purpose. Electrophoretic mobility
      shift assays (EMSA) have proven to be simpler and more rapid. Although EMSA can
      separate triplex and duplex complexes, there is concern that this technique does
      not afford as rigorous an equilibrium measurement as is provided by QDFA. We show
      that QDFA and EMSA techniques provide Kd estimates that agree within one order of
      magnitude under common experimental conditions. Agreement is best in buffers with
      low concentrations of monovalent cations. Surprisingly, EMSA appears to slightly
      overestimate triplex stabilities relative to QDFA in the presence of
      physiological concentrations of monovalent cations (100 mM). Under these
      conditions, agreement between the techniques can be improved by quenching EMSA
      samples with excess unlabeled competitor duplex just prior to gel loading. The
      data suggest that EMSA can provide results in reasonable agreement with QDFA and
      offer some insight into sources of deviation between the two methods.

PMID- 9025949
TI  - Synthesis and utilization of GDP-D-arabinopyranoside.
AB  - We describe a procedure for the enzymatic synthesis of labeled or unlabeled GDP-D
      arabinopyranoside. This method uses two enzymes purified from pig kidney: an L
      fucokinase and a GDP-L-fucose pyrophosphorylase. The isolated GDP-D-[3H]arabinose
      served as a precursor for arabinose addition to lipophosphoglycan (LPG) of
      Leishmania major, using a parasite membrane fraction as the source of
      arabinosyltransferase. The procedures described provide a useful means for
      obtaining radiolabeled GDP-D-arabinopyranoside to study synthesis of D
      arabinopyranoside-containing glycoconjugates.

PMID- 9025950
TI  - Domain-directed polymerase chain reaction capable of distinguishing bacterial
      from host DNA at the single-cell level: characterization of a systematic method
      to investigate putative bacterial infection in idiopathic disease.
AB  - The use of a broad-range PCR to target conserved sequences in the bacterial
      ribosome has long been recognized as an approach to investigating idiopathic
      human diseases for the presence of bacteria. An important example is rheumatoid
      arthritis where the hypothesis of a bacterial etiology remains viable despite
      failure of previous methods to identify a causative organism. Practical
      implementation of this strategy, however, was impeded by requirements unique to
      the study of these diseases. Hence, an adequately characterized method for
      achieving this has not appeared. We now describe such a method based on the use
      of a broadly reactive pair of deoxyinosine-containing primers. Detailed
      characterization addressing these requirements provided evidence that DNA from at
      least 96% of potential prokaryotic pathogens would be detected. The sensitivity
      was shown to approximate that of a single organism per reaction. Importantly,
      this sensitivity was shown to be maintained among multiple targets and to be
      unimpaired by a large excess of human DNA. Similar results were obtained with
      extracts of inflamed human synovial fluid to which as little as 0.01 pg of
      bacterial DNA or, alternately, a single organism per reaction was added. This
      method was also shown correctly to detect the causative bacteria in clinically
      infected synovial fluids, further documenting its applicability to such
      specimens. Finally, it was converted to an in situ method by which bacterial
      sequences were histochemically localized to Michaelis-Guttman bodies in tissue
      sections from a patient with malakoplakia, a poorly understood infectious
      disease. The broad reactivity and high sensitivity achieved by this approach
      translate into a high likelihood of detecting an unknown bacterium if present in
      a clinical specimen. Conversely, if properly controlled, the failure of this
      method to detect such organisms can provide evidence supporting rejection of the
      bacterial etiology hypothesis, an important aspect unique to this approach. For
      those bacterial sequences that are detected, the ability to localize them in situ
      would help define their histologic context and hence facilitate their
      pathogenetic interpretation. The present method should therefore be appropriate
      for use in systematically studying rheumatoid arthritis as well as a number of
      other important idiopathic disorders where a bacterial etiology is suspect.

PMID- 9025951
TI  - A chemiluminescent microtiter plate assay for sensitive detection of protein
      kinase activity.
AB  - A chemiluminescent protein kinase assay using biotinylated substrate peptides
      captured on a streptavidin-coated microtiter plate and monoclonal antibodies to
      detect their phosphorylation is described. Assay conditions were optimized and
      validated for sensitive measurement of protein kinase A, protein kinase C,
      Ca2+/calmodulin-dependent protein kinase II (CAM-KII), receptor interacting
      protein, and src activities. The newly developed chemiluminescent assay has
      several advantages over currently used radioactive or colorimetric methods. It is
      highly sensitive at low enzyme and substrate concentrations and high, close to
      physiological ATP levels. It is fast, simple to perform and amenable to
      automation and high-throughput drug screening. The assay is also robust,
      exhibiting minimum interference from solvents and test substances from various
      sources. Overall, among the presently available methods for the detection of
      protein kinase activity, chemiluminescence was found to provide the highest
      sensitivity under conditions most closely mimicking the intracellular
      environment. This assay is expected to be useful in both academic and industrial
      laboratories, especially in identifying novel classes of protein kinase
      inhibitors.

PMID- 9025952
TI  - Ceramide profiling of complex lipid mixtures by electrospray ionization mass
      spectrometry.
AB  - Ceramides and sphingoid bases are important intracellular second messengers that
      play a role in the regulation of cell growth, differentiation, and programmed
      cell death. Until now, quantitative and qualitative analysis of ceramide second
      messengers has been limited by a lack of analytical methods capable of detecting
      endogenous levels of, and differentiating between, individual ceramide species.
      Here we report the use of electrospray ionization tandem mass spectrometry for
      the qualitative and quantitative analysis of ceramides. Collision-induced
      fragmentation resulted in characteristic product ions for the sphingosine and
      dihydrosphingosine (sphinganine) head groups at m/z 264 and 282 and m/z 266 and
      284, respectively, regardless of the length of the fatty acyl chains, with
      spectra being reproducible at concentrations as low as 25 nM (25
      fmol/microliter). These reporter ions were used to detect both sphingosine- and
      sphinganine-based ceramides in complex mixtures using precursor ion scan
      analysis. We demonstrated the application of this method for profiling the
      composition of ceramides in a commercial preparation of bovine brain ceramides
      and, following minimal chromatographic separation, a lipid extract of cultured T
      cells. Furthermore, we easily detected relative differences in individual
      ceramide species levels by comparing the profiles of three related lymphocyte
      cell lines, Jurkat, U937, and WEHI 231. Finally, by the addition of a
      nonnaturally occurring internal standard, we show that the technique can be used
      to measure quantitative changes in ceramide levels in such biologically derived
      lipid preparations.

PMID- 9025953
TI  - A spectrophotometric assay for the enzymatic demethoxylation of pectins and the
      determination of pectinesterase activity.
AB  - A rapid spectrophotometric method for the determination of pectinesterase
      activity is presented. In this assay, methanol released from pectin by
      pectinesterase is oxidized with alcohol oxidase to form hydrogen peroxide and
      formaldehyde. Hydrogen peroxide is then quantitated with peroxidase and the
      chromogen 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). Since both
      reactions exhibit the same pH optimum it was possible to couple the methanol
      assay directly to the action of pectinesterase for the real-time determination of
      this enzyme. The assay is reliable and sensitive, being capable of quantitating a
      minimum pectinesterase activity of 0.0625 unit (1 unit = 1 microM methanol
      released per minute). It is also capable of detecting the enzymatic
      demethoxylation of galactopyranosyl uronic acid methyl esters of pectin down to a
      minimum concentration of 1.56 nM of methanol per milliliter using a pectin
      substrate with a methoxy content of 10% (w/w) at a concentration of 0.5
      microgram/ml.

PMID- 9025954
TI  - Detection of single-base changes using a bioluminometric primer extension assay.
AB  - A rapid bioluminometric technique for real-time detection of known single-base
      changes is presented. The concept relies on the measurement of the difference in
      primer extension efficiency by a DNA polymerase of a matched over a mismatched 3'
      terminal. The rate of the DNA polymerase-catalyzed primer extension is measured
      by an enzymatic luminometric inorganic pyrophosphate (PPi) detection assay
      (ELIDA) (P. Nyren (1987) Anal. Biochem. 167, 235-238). The PPi formed in the
      polymerization reaction is converted to ATP by ATP sulfurylase and the ATP
      production is continuously monitored by the firefly luciferase. In the single
      base detection assay, immobilized single-stranded DNA fragments are used as
      template. Two detection primers differing with one base at the 3' end are
      designed, one precisely complementary to the nonmutated DNA sequence and the
      other precisely complementary to the mutated DNA sequence. The primers are
      hybridized with the 3'-termini over the base of interest and the primer extension
      rates are, after incubation with DNA polymerase and deoxynucleotides, measured
      with the ELIDA. We show that the relative mismatch extension efficiency is
      strongly decreased by substituting the alpha-thiotriphosphate analog for the next
      correct natural deoxynucleotide after the 3'-mismatch termini. The possibility of
      using the technique for studies of mismatch extension kinetics for two
      polymerases lacking exonucleolytic activity is shown.

PMID- 9025955
TI  - A selective immunoaffinity chromatography for determination of plasma 1 alpha, 25
      dihydroxyvitamin D3: application of specific antibodies raised against a 1 alpha,
      25-dihydroxyvitamin D3-bovine serum albumin conjugate linked through the 11 alpha
      position.
AB  - A selective and simple immunoaffinity chromatography of 1 alpha, 25
      dihydroxyvitamin D3 has been developed and found to be a useful pretreatment tool
      for determining the metabolite in human plasma. A reasonably designed, haptenic
      derivative, 11 alpha-hemiglutaryloxy-1 alpha, 25-dihydroxyvitamin D3, was linked
      to bovine serum albumin, and rabbits were immunized repeatedly with the
      conjugate. The resulting polyclonal antibodies were specific to 1 alpha, 25
      dihydroxyvitamin D3, recognizing both the A-ring and the side-chain structures.
      The antibodies were then immobilized on agarose gel to produce an immunosorbent
      which was stable and repeatedly usable. A plasma extract prepared with a Chem
      Elut column was applied to an affinity column containing the immunosorbent. After
      adequate washing, the adsorbed 1 alpha, 25-dihydroxyvitamin D3 was eluted
      selectively with a satisfactory recovery rate. This immunoaffinity chromatography
      enabled a simple radioreceptor assay for human plasma 1 alpha, 25
      dihydroxyvitamin D3 which does not require any preparative high-performance
      liquid chromatography. The mean (+/-SD) values for 30 normal subjects and 8
      patients with chronic renal failure were 36.0 (10.2) and 13.1 (2.1) pg/ml,
      respectively. The present method also gave reliable assay values for the plasma
      specimens from 1 alpha-hydroxyvitamin D3-administered volunteers, which have
      conventionally been difficult to measure unless complicated pretreatment is used.

PMID- 9025956
TI  - A continuous spectrophotometric assay for monoamine oxidase and related enzymes
      in tissue homogenates.
AB  - A continuous, peroxidase-linked spectrophotometric assay is described which is
      suitable for measuring monoamine and diamine oxidase and semicarbazide-sensitive
      amine oxidase activities in tissue homogenates. In the assay, 4-aminoantipyrine
      is oxidized and then condenses with vanillic acid to give a red quinoneimine dye.
      The absorbance at 498 nm is proportional to the amount of hydrogen peroxide
      released in the amine oxidase reaction. The molar absorption coefficient of the
      dye at pH 7.6 was 4654 M-1 cm-1. The method is suitable for use with any amine
      oxidase substrate which has a higher oxidation-reduction potential than does 4
      aminoantipyrine. Following preincubation of rat liver homogenates with selective
      monoamine oxidase (MAO)-A and -B inhibitors, kinetic constants were obtained for
      metabolism of the mixed substrate, p-tyramine. Inhibition of MAO in rat liver
      homogenates was also measured following administration of the antidepressant,
      phenelzine. This inexpensive assay which employs reagents with low toxicity can
      thus be used to determine the degree of inhibition of MAO elicited by potential
      antidepressant and anti-parkinsonian agents. Drugs, their metabolites, and
      environmental toxins can also be screened as possible amine oxidase substrates or
      inhibitors, and kinetic constants for turnover of novel substrates can be
      determined.

PMID- 9025958
TI  - Taq-amplified fragments appear as doublets in denaturing gradient gels.

PMID- 9025957
TI  - Quantitative determination of amino acid levels in neutral and glucosamine
      containing carbohydrate polymers.
AB  - Low-level (subanomole) determination of amino acids in samples of naturally
      derived polymeric carbohydrates has been demonstrated using vapor-phase acid
      hydrolysis and subsequent precolumn derivatization with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate. Application has been demonstrated for neutral
      polysaccharide polymers such as laminarin (beta-1,3; branched), curdland (beta
      1,3; unbranched), pullulan (alpha-1, 6-maltotriose), glycogen (alpha-1,4-glucan),
      and inulin (polyfructose). Successful determination (acceptable recovery and lack
      of interferences) was possible in samples which also contained up to roughly 50
      micrograms amino sugars (e.g., chitosan or glucans with copurified glucosamine
      oligomers), although optimum utility is for samples containing up to ca. 10
      micrograms total amines. The limit of quantification was roughly 20 ng protein/
      mg sample, based on analysis of reagent blanks, although the limit of detection
      was much lower (ca. 0.1 ng protein/mg sample). Incorporation of a relatively
      rapid hydrolysis (150 degrees C for 1.5 h) gave similar results to use of 110
      degrees C for 24 h and allowed for relatively rapid processing. The method has
      shown good sensitivity, linearity, ruggedness, and ease. Recovery has been
      optimized, although yield varied somewhat depending on polymer composition.

PMID- 9025960
TI  - Increasing the sensitivity of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate
      amino acid analysis: a simple solution.

PMID- 9025959
TI  - In vitro generation of competitor DNA segments for the quantitation of any
      nucleic acid of known sequence by competitive polymerase chain reaction.

PMID- 9025961
TI  - Method for detecting glutathione reductase activity on native activity gels which
      eliminates the background diaphorase activity.

PMID- 9025962
TI  - Detection of S-nitrosothiols and other nitric oxide derivatives by photolysis
      chemiluminescence spectrometry.
AB  - We have developed a method for the detection of biologically relevant derivatives
      of NO. that couples photolysis to chemiluminescence. S-Nitrosothiols, N-nitroso-L
      tryptophan, and iron-nitrosyl derivatives can all be detected by this
      methodology, and these derivatives can be distinguished from free NO. by making
      measurements with and without photolysis. The limits of detection of this system
      are in the 10 nM range, with an intraassay variability of less than 2% and an
      interassay variability of less than 1.5%. The use of cutoff filters and
      alterations in pH and flow rate through the photolysis cell provide additional
      useful parameters with which to characterize specific NO. derivatives based on
      their intrinsic stability. This methodology is a useful addition to the growing
      armamentarium of techniques used to characterize the biochemistry and metabolism
      of NO..

PMID- 9025963
TI  - Direct determination of dipyridamole in serum.
AB  - A new method for the determination of dipyridamole in serum for concentrations
      between 10 and 100 ng ml-1 by means of matrix isopotential synchronous
      fluorescence spectrometry and derivative techniques is proposed. This new method
      is useful for the determination of compounds in samples with unknown background
      fluorescence, such as dipyridamole in serum, without the need for tedious
      preseparation. The determination was performed in an ethanol/water medium (15%
      v/v) at a pH value of 10.0, provided by adding an ammonium chloride/ammonia
      buffer solution. Since dipyridamole is a stimulant which is very much used like a
      doping substance in sport, the method was successfully applied to the
      determination of dipyridamole in serum. Better sensitivity and repeatability are
      achieved for these matrices than with the fluorometric ones described in the
      literature. An exhaustive statistical analysis has been developed for all
      calibration graphs. This treatment includes robust regression such as least
      median of squares which also detects outliers and leverage points. The overall
      least-squares regression has been applied to find the more exact straight line
      which fits the experimental data. The error propagation has been considered to
      calculate the detection limit, determination limit, and the repeatability of the
      method.

PMID- 9025964
TI  - Monitoring papain digestion of a monoclonal antibody by electrospray ionization
      mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) has been used to examine the
      Fab, F(ab')2 and deglycosylated Fc fragments obtained from the murine IgG1 B72.3
      monoclonal antibody (MAb) by digestion with the sulfhydryl protease papain, in an
      attempt to determine the sites of cleavage and thus to clarify the mode of action
      of this enzyme on MAbs. ESI analysis of the Fab and F(ab')2 subunits indicated
      that the predominant site of papain cleavage occurred at C221 of the B72.3 MAb
      heavy chain. Reduction of the intra- and interchain disulfide bridges of these
      fragments by 1,4-dithiothreitol and subsequent electrospray analysis showed a
      loss of C221 from the C-terminal end of the Fd subunit. ESI analysis of the
      cleaved Fab fragment indicated that there was an apparent loss of amino acid
      residues from this fragment. Edman sequencing of the cleaved subunit revealed an
      intact light chain and the loss of QVQ from the N-terminal of the Fd subunit.
      Reduction of this subunit gave a Fd fragment approximately 32 Da greater than the
      predicted mass, which we have attributed to oxidation of the heavy chain
      methionine residues (M81 and M136). Removal of the carbohydrate portion from the
      Fc fragment by N-glycosidase F indicated that papain cleavage had occurred at
      C223 of the B72.3 MAb heavy chain. In addition, it was observed that the C
      terminal lysine residue (K438) was absent from the deglycosylated Fc fragment,
      presumably due to carboxypeptidase B activity that occurs during the in vivo
      production of the B72.3 MAb in murine hosts. These data clearly illustrate the
      power of ESI-MS for determining small changes in mass on large proteins as well
      as providing a rapid and sensitive technique for assessing MAb fragments prior to
      use in radioimaging or radiotherapy.

PMID- 9025965
TI  - Potential misevaluation of the ground-state dissociation constant from
      fluorimetric titrations: application to the ion indicators SBFI, PBFI, and fura
      2.
AB  - A test based on time-resolved fluorescence experiments is proposed to assess the
      interference of an excited-state reaction with the fluorimetric determination of
      the ground-state dissociation constant Kd of ion [symbol: see text] fluorescent
      indicator complexes. If an inflection point occurs in the plot of the
      fluorescence signal vs -log [ion] in the concentration range of the ion where
      both decay times are invariant, this inflection point can be associated with the
      correct Kd. In contrast, the inflection point(s) in the concentration range where
      the decay times vary cannot be attributed to Kd. The test is applied to the
      fluorescent ion indicators SBFI (for Na+), PBFI (for K+), and Fura-2 (for Ca2+).
      In all three cases the decay times are invariant in the physiological
      concentration ranges of the respective ions, indicating that the fluorimetrically
      determined Kd values are actually the true Kd values.

PMID- 9025966
TI  - Organic solvent systems for 31P nuclear magnetic resonance analysis of lecithin
      phospholipids: applications to two-dimensional gradient-enhanced 1H-detected
      heteronuclear multiple quantum coherence experiments.
AB  - 31P NMR of lipid extracts is a reproducible, rapid, and nondegradative method for
      qualitative and quantitative analyses of phospholipid mixtures. This analysis,
      however, is hampered by the instability of the solvent system commonly used for
      NMR spectroscopy (CHCl3/ CH3OH/H2O-EDTA). In this work we have investigated the
      effects of several monophasic solvent mixtures to overcome this disadvantage.
      Among these mixtures we have selected a solution of triethylamine,
      dimethylformamide, and guanidinium chloride (Et3N/DMF-GH+) as the most efficient
      system. In this solvent the chemical shift dispersion of the 31P signals is about
      four times the frequency range observed in the standard chloroform-methanol-water
      system. Moreover, the stability of this solvent, as a monophasic system, allows
      easy reproducibility of the analysis. The use of two-dimensional 1H-31P gradient
      enhanced heteronuclear multiple quantum coherence experiments can further exploit
      the higher resolution of the signals obtained with this solvent system for the
      structure elucidation of known and unidentified phospholipids.

PMID- 9025968
TI  - Determination of catalase activity at physiological hydrogen peroxide
      concentrations.
AB  - A method for the determination of catalase activity (EC 1.11.1.6.) in homogenates
      and cell suspensions is described by following the decomposition of H2O2 at
      physiological H2O2 levels. This first chemiluminescence assay for catalase
      activity is based on the reaction of luminol (5-amino-2,3-dihydro-1,4
      phthalazinedione) and NaOCl. The chemiluminescence of this reaction specifically
      depends on the H2O2 concentration and shows fast kinetics of less than 2 s. Using
      a flow technique, the exponential decay of H2O2 in the presence of catalase is
      followed down to 10(-8) M H2O2 at pH 7.4 over three orders of magnitude. At these
      very low H2O2 concentrations neither oxygen is liberated in gaseous form nor
      enzyme inactivation or loss of cell viability is observed. Addition of the
      catalase inhibitor NaN3 completely inhibits H2O2 decomposition. Since the method
      is not influenced by sulfhydryl and amino group containing compounds, it is
      especially suited for crude tissue homogenates and suspensions of intact cells.
      Interestingly, application to cell suspensions shows that intact human
      erythrocytes and rat hepatocytes exhibit only 5.8 and 1.9% of catalase activity
      when compared to homogenized cells. These data suggest that the diffusion of H2O2
      through membranes is lower than that assumed so far.

PMID- 9025967
TI  - DD/AP-PCR: combination of differential display and arbitrarily primed PCR of
      oligo(dT) cDNA.
AB  - In this report we describe the first direct comparison of differential display
      (DD) and arbitrarily primed PCR (AP-PCR) amplification of oligo(dT)-primed cDNA.
      Our results indicate that both of these widely used RNA fingerprinting techniques
      have their respective advantages and limitations. DD produces profiles specific
      to the anchored oligo(dT) primer used for cDNA synthesis. AP-PCR displays
      significant redundancy of profiles generated from different oligo(dT) cDNA pools,
      but is not as biased to the isolation of A/T-rich or 3' sequences. It was found
      that both techniques can utilize cDNA synthesized using a generic anchored
      oligo(dT) primer (dT12VN; equimolar amounts of dT12VA, dT12VC, dT12VG, and
      dT12VT, where V is dA, dC, or dG); this efficiently selects for poly(A)+
      sequences from total RNA, and significantly reduces the number of cDNA
      preparations required per experiment. Using dT12VN cDNA pools generated from rat
      liver, spleen, and brain, the two approaches (AP-PCR and DD) were used in
      combination. Several known mRNAs were identified; some were unique to either
      technique and some were common to both. Since it is the RNA which is usually the
      limiting resource, maximum utilization may be achieved by generating a single
      pool of dT12VN-primed cDNA and performing both AP-PCR and DD (DD/AP-PCR).

PMID- 9025969
TI  - Synthesis of the photoaffinity label [1'-14C]-6C-(azimethyl)octylglucoside and
      its reaction with isolated renal brush border membranes.
AB  - We describe the synthesis of the photolabile analog of n-octylglucoside (OG), 6C
      (azimethyl)octylglucoside (diazirino-octylglucoside, DOG). This diazirino
      derivative (lambda max = 335 nm) can be activated with long-wavelength UV to
      generate a highly reactive carbene, an intermediate suitable for a covalent
      ligand-receptor linkage. In inhibitor studies on D-glucose uptake into rabbit
      renal brush border membrane vesicles (BBMV) DOG showed a competitive inhibition
      with regard to D-glucose with a Ki of 20 +/- 5 microM, which was not
      significantly different from that of the template compound OG (Ki = 30 +/- 10
      microM). On irradiation (lambda max = 350 nm) of BBMV in the presence of
      [14C]DOG, proteins of 61, 72 to 78, and 95 kDa were labeled by photoinduction. A
      band of 73 kDa was also positive in Western blots using an anti-Na+/D-glucose
      cotransporter antibody. Further investigations revealed that the labeled proteins
      were presumably mainly glucosidases known to be present in high concentration in
      renal BBMV. By comparison with authentic material one of the labeled proteins (61
      kDa) was identified as trehalase (EC 3.2.1.28). These studies suggest that labels
      such as DOG carrying the reactive group directly at the D-glucose moiety of the
      molecule can be used to label proteins with carbohydrate recognition sites.

PMID- 9025970
TI  - Fluorimetric detection of aldehyde dehydrogenase activity in human blood, saliva,
      and organ biopsies and kinetic differentiation between class I and class III
      isozymes.
AB  - Two highly fluorogenic aldehydes, 7-methoxy-1-naphthaldehyde (MONAL-71) and 6
      methoxy-2-naphthaldehyde (MONAL-62), were examined as indicators of the aldehyde
      dehydrogenase (ALDH) activity in human tissue homogenates and accessible body
      fluids. Both compounds were previously found to be excellent substrates for the
      ALDH from erythrocytes and for the purified class I (cytosolic) ALDH from human
      liver. By contrast, only MONAL-62, but not the isomeric MONAL-71, was oxidized by
      class III ALDH present in human saliva. The apparent Km for the former compound
      reacting with salvia ALDH is 0.24 microM, with the reaction rate (Vmax) close to
      that of benzaldehyde oxidation. There is also a fully competitive inhibition of
      the fluorogenic oxidation of the MONAL-62 by benzaldehyde. Both NAD+ and NADP+
      can be used as oxidants in this reaction, with comparable rates, a fact
      previously reported for the human class III aldehyde dehydrogenase. In human
      liver homogenate (cytosolic + microsomal fraction), the ALDH activity is easily
      detectable using either MONAL-71 or MONAL-62, with specific activities of
      approximately 2.5 and 3.2 units per gram of protein, respectively. The low
      apparent Km values, 0.85 and < 0.03 microM, respectively, together with the
      inhibition profile by propionic aldehyde (ID50 in the micromolar range) indicate
      that both compounds are oxidized primarily by the class I ALDH, further confirmed
      by low activity (0.4 U/g) with NADP+ as oxidant. By contrast, in human stomach,
      containing mostly class III ALDH, the activity measured with MONAL-71, 0.4 U/g,
      is much lower than that with MONAL-62 (5.1 U/g with NAD+ and 3.1 U/g with NADP+),
      the latter being virtually insensitive to 1 mM propionic aldehyde. Hence, in a
      stomach homogenate, class I and class III ALDH activities can be measured
      selectively with the two fluorogenic substrates described. In all experiments,
      the activity of aldehyde oxidase was at least 10-fold lower than that of the
      ALDH. Addition of 5 mM 4-methylpyrazole, a known inhibitor of the alcohol
      dehydrogenase, did not change the resultant ALDH activities by more than 10%,
      indicating lack of interference by the former enzyme. A preliminary screening of
      two liver tumour samples showed diminished class I ALDH activities (0.7 and 0.03
      U/g), but no evidence for class III ALDH induction. The above observations are
      discussed in relation to the mechanism of detoxication of cyclophosphamide.

PMID- 9025971
TI  - Analysis of single-strand conformation polymorphism by capillary electrophoresis
      with laser-induced fluorescence detection using short-chain polyacrylamide as
      sieving medium.
AB  - A rapid analysis of single-strand conformation polymorphism (SSCP) by capillary
      electrophoresis with laser-induced fluorescence (CE-LIF) detector was developed
      using a short-chain, linear polyacrylamide (PA) as sieving medium. Capillary
      filling of this low-viscosity medium and medium replacement were carried out by
      commercial capillary electrophoresis instruments. The approach was successfully
      applied to detect the C677T mutation of methylenetetrahydrofolate reductase gene.
      The influences of factors such as the concentration of polymers, voltage,
      temperature, and additives on the SSCP analysis were systematically investigated.
      Using 6% PA sieving medium and high electric field, four strands were resolved
      within 11 min in a DNA sample heterozygous for the C677T mutation, and a
      characteristic pattern was apparent for each of the three genotypes. When using
      multiple injection mode, the average analysis time per sample was reduced to
      about 4 min. In conclusion, our results indicate that CE-LIF may be an
      alternative to conventional SSCP analysis based on slab gel electrophoresis for
      the detection of genetic mutations. The technique is simple and rapid and is well
      suited to analysis of large numbers of clinical samples.

PMID- 9025972
TI  - Sequestration stabilizes lac repressor-DNA complexes during gel electrophoresis.
AB  - The gel electrophoresis mobility shift assay is widely used for both qualitative
      and quantitative characterization of protein-nucleic acid interactions. Often it
      is found that protein-nucleic acid complexes persist within gels for much longer
      than would be expected on the basis of their free solution lifetimes. Excluded
      volume and matrix-interaction mechanisms have been proposed to account for the
      enhanced stabilities of complexes within gels. To test these mechanisms, we have
      investigated the influences of gel composition and concentration on the pseudo
      first-order dissociation kinetics of complexes containing the Escherichia coli
      lactose (lac) repressor protein and lactose promoter DNA. In both polyacrylamide
      and agarose gels, dissociation rates were slower than those in free solution and
      decreased with increasing gel concentration. This result is inconsistent with
      mechanisms of stabilization that require specific interactions with the gel
      matrix. Under standard reaction conditions, free solution values of kdiss were
      proportional to [DNA]0.83 +/- 0.11, while in 10% polyacrylamide gels kdiss values
      were proportional to [DNA]0.48 +/- 0.09. These results suggest that the lifetimes
      of lac repressor-DNA complexes in free solution are limited by their encounter
      frequency with molecules of DNA or with protein-DNA complexes; some or all of the
      stabilization observed in gels may be due to a reduction in this frequency.

PMID- 9025973
TI  - Measurement of myeloperoxidase in leukocyte-containing tissues.
AB  - An improved method is reported for measurement of myeloperoxidase (MPO) activity
      in tissues. While spectrophotometric methods based on oxidation of O-dianisidine
      or other dyes have been reported for MPO measurement in pure polymorphonuclear
      leukocytes (PMNs), these methods often fail to accurately assay MPO activity in
      tissues. We observe that tissue myoglobin or vascular hemoglobin markedly effects
      the spectrophotometric assay for MPO. Under optimal conditions of 0.53 mM O
      dianisidine, 0.15 mM H2O2, pH 6.0, either myoglobin or hemoglobin produced
      absorbance at 460 nm in a concentration-dependent manner similar to that of MPO.
      In perfused heart tissue, myoglobin caused a major problem with the assay
      resulting in an inability to obtain accurate linear results as a function of MPO
      concentration and PMN number. To eliminate the effect of tissue myoglobin or
      vascular hemoglobin on the assay, one-step gel filtration chromatography of
      tissue extracts was introduced. MPO, myoglobin, and hemoglobin were easily
      separated using a Sephadex G-75 column according to the difference in their
      molecular weights. A linear relationship between the MPO activity and PMN number
      was observed only after processing the tissue extracts through the Sephadex G-75
      column. Thus, MPO activity in PMN-containing tissues can be precisely quantitated
      after one-step purification on a molecular exclusion column. Enzyme purification
      with removal of myoglobin is essential for obtaining accurate measurement of MPO
      activity and quantitation of PMNs in muscle tissue.

PMID- 9025974
TI  - Determination of 2-keto-3-deoxyoctulosonic acid (KDO) with high-performance anion
      exchange chromatography (HPAEC): survey of stability of KDO and optimal
      hydrolytic conditions.
AB  - A new method for 2-keto-3-deoxy-octulosonic acid (KDO) determination using high
      performance anion-exchange chromatography was developed. KDO is well separated
      from Neu5Ac, and the response was linear from 20 pmol to 5 nmol. The method was
      used to examine the stability of KDO under various hydrolytic, conditions and to
      survey optimal hydrolytic conditions for release of KDO.

PMID- 9025975
TI  - A microplate receptor assay for the amnesic shellfish poisoning toxin, domoic
      acid, utilizing a cloned glutamate receptor.

PMID- 9025976
TI  - Restriction mapping of recombinant cosmid clones using lambda terminase and field
      inversion gel electrophoresis.

PMID- 9025977
TI  - Purification of the T-cell receptor zeta-chain: covalent modification by 4-(2
      aminoethyl)-benzenesulfonyl fluoride.

PMID- 9025978
TI  - A critical parameter determining the aging of DNA-calcium-phosphate precipitates.

PMID- 9025979
TI  - A powerful approach for generating and sequencing DNA deletions: sequencing from
      the outside in.

PMID- 9025980
TI  - The Marrara syndrome: a hypersensitivity reaction of the upper respiratory tract
      and buccopharyngeal mucosa to nymphs of Linguatula serrata.
AB  - The Marrara syndrome, like Halazoun in Lebanon, is a hypersensitivity reaction of
      the upper respiratory tract and buccopharyngeal mucosa to nymphs of Linguatula
      serrata. The condition follows the consumption of Marrara which consists of raw
      liver, lungs, trachea and rumen of goats and sheep infected with larvae of L.
      serrata. The adult worm is found in the nasal passages of dogs. Sheep and goats
      are infected by eggs from infected dogs. A survey that included 240 adult
      individuals in a village of endemic L. serrata infection in the Sudan showed that
      20% experienced symptoms of allergic nasopharyngitis (Marrara syndrome) following
      the consumption of raw viscera of goats or sheep at least once in their life. In
      a prospective study of 24 patients who reported to hospital with the Marrara
      syndrome, the clinical features included itching in the throat and nose,
      unilateral conductive deafness, tinnitus and facial palsy. Secondary bacterial
      infection caused suppurative otitis media. Adult L. serrata parasites were found
      in the nasal passages of 56 and 47% of male and female dogs in the endemic area.
      Nymphs were recovered from the mesenteric lymph nodes, lungs and livers of goats
      in the area.

PMID- 9025981
TI  - High prevalence of chloroquine resistant Plasmodium falciparum infection in
      Rajasthan epidemic.
AB  - Plasmodium falciparum is the main killer among all human malaria parasites. In
      1994, there was a falciparum malaria epidemic in Rajasthan, India, with many
      deaths. We have investigated active falciparum malaria cases from this epidemic
      and found that most of the parasite isolates (95%) were resistant to chloroquine.
      Nevertheless, all the tested isolates from the epidemic, were sensitive to
      mefloquine and quinine and ninety percent were also susceptible to
      sulfadoxine/pyrimethamine. Most individuals had moderate levels of TNF-alpha (20
      220 pg/ml) and anti-parasite IgM antibodies compared to IgG levels which were
      relatively lower. In conclusion, the high transmission rate of the chloroquine
      resistant P. falciparum parasite could be the probable cause of the disease
      epidemic in Rajasthan. The timely drug sensitivity test and availability of
      appropriate antimalarial drugs are, therefore, warranted.

PMID- 9025982
TI  - Rapid delineation of closely-related filarial parasites using genetic markers in
      spacer rDNA.
AB  - Two closely-related species of filarial parasite, Litomosoides galizai and L.
      sigmodontis, were characterised using a polymerase chain reaction-linked
      restriction fragment length polymorphism (PCR-RFLP) technique. The rDNA region
      spanning the first and second internal transcribed spacers as well as the 5.8S
      gene (ITS+) was amplified by PCR from each of the species using conserved primers
      to the 18S and 28S ribosomal genes, digested separately with a range of
      restriction endonucleases and the fragments separated by agarose gel
      electrophoresis. PCR-RFLP of ITS+ using endonucleases Alu I, Cfo I, Dra I, Rsa I
      and Vsp I produced characteristic patterns for each species. No variation in RFLP
      patterns was detected among different DNA sample preparations or the sexes of
      each species. The present study demonstrates that the ITS+ provides genetic
      markers for the differentiation of L. galizai from L sigmodontis and suggests
      that internal transcribed spacer rDNA may provide species markers for other
      filarioid nematodes. Such markers have implications for diagnosis and for
      studying the biology, pathogenesis and systematics of filarial parasites.

PMID- 9025983
TI  - Epitopes common to Trypanosoma cruzi and mammalian tissues are recognized by sera
      from Chagas' disease patients: prognosis value in Chagas disease.
AB  - Monoclonal antibodies (MoAbs) raised against Trypanosoma cruzi microsomal
      fraction (Mc) and cross-reactive with mammalian tissues were used to evaluate the
      ability of cross-reactive T. cruzi antigens to induce an immune response in
      Chagas' disease. Thus, we studied the ability of sera from Chagas' disease
      patients (CDP) with different degrees of cardiac dysfunction to block the immune
      recognition of these MoAb to the target antigen determining for each serum an
      inhibition index (II). By means of this approach we inferred that blocking of
      monoclonal antibody binding to T. cruzi microsomes by subjects' serum represents
      antibodies with the same reactivity. After serological and medical examinations,
      individuals were separated into the following groups: Chagas' disease patients
      without manifest cardiac involvement (CDP-0), CDP with suspected or borderline
      cardiac disease (CDP-1), CDP with moderate myocardial dysfunction (CDP-2), CDP
      with overt cardiac dysfunction (CDP-3) and controls including healthy subjects
      (HS) and patients with idiopathic myocarditis (IMP). The reactivity between MoAb
      5F2 and its target antigen was significantly (p < 0.05) inhibited by sera from
      CDP irrespective of the clinical stage [CDP: n = 46, 50 +/- 20, mean II +/- SD:
      control: n = 16, 18 +/- 8]. Moreover, 5F2 was able to distinguish (p < 0.05) sera
      from CDP with mild disease (CDP clinical grade 0/1: n = 26, 34 +/- 18) from that
      of CDP with severe disease (CDP clinical grade 2/3: n = 20, 67 +/- 7). Moreover,
      the inhibitory capacity of sera from asymptomatic CDP (CDP-0) correlated with
      patients age (r = 0.66, p < 0.05). CDP-0 below or equal 40 years of age had
      results (n = 15, 25 +/- 13) comparable (p > 0.05) to that of controls while mean
      inhibition of CDP-0 over 40 years of age (n = 5, 60 +/- 5) was indistinguishable
      (p > 0.05) from that of patients with severe disease. Competitive assay with MoAb
      5A9B11 also showed significant differences (p < 0.05) between sera from CDP (n =
      46, 46 +/- 24) and controls (n = 13, 5 +/- 5). On the contrary, the differences
      observed between CDP with different cardiac involvement was not significant
      (mild: n = 26, 31 +/- 22; severe: n = 20, 66 +/- 11). However a thorough study of
      data from asymptomatic sera revealed the existence of two levels of reactivity,
      with low and high capacity to inhibit the reaction of 5A9B11 against Mc. On the
      contrary, CDP sera showed a blocking activity for 1A10C11 comparable to that of
      controls (CDP: n = 25, 19 +/- 9; control: n = 12, 14 +/- 6). Some cross-reactive
      MoAbs recognized epitopes partially composed of carbohydrates. Interestingly, 5F2
      and 5A9B11 epitopes did not appear to have carbohydrates moieties. In summary,
      immunoinhibition assays revealed differences in the immune response of chronic
      chagasic patients against parasite epitopes. These results have opened the
      possibility to identify a prognosis marker of the disease suggesting the clinical
      utility of monitoring levels of these anti-Mc antibodies in patients with chronic
      Chagas' disease.

PMID- 9025984
TI  - Trypanosoma cruzi rRNA genes: a repeated element from the non-transcribed spacer
      is locus specific.
AB  - To determine the occurrence of conserved domains of presumed functional
      selection, a genomic restriction analysis was carried out in the region
      surrounding a transcription start point (tsp) from the rRNA cistron in T. cruzi.
      The transcribed spacer was found highly conserved among several isolates, whereas
      at 146 bp upstream from the tsp a highly polymorphic pattern was evidenced with a
      probe that contains sequences of a repetitive element (172 bp). Both genomic and
      chromosomal hybridizations indicated the linkage of the repetitive element to
      coding regions of the rRNA cistron. This represents the first example of a
      repetitive element not interspersed throughout the genome of T. cruzi, and
      strongly suggests that a functional role is being selected.

PMID- 9025985
TI  - Serum levels of eosinophil cationic protein, eosinophil-derived neurotoxin and
      myeloperoxidase in infections with filariae and schistosomes.
AB  - The serum levels of three major granulocyte proteins were measured in patients
      with onchocerciasis, bancroftian filariasis and intestinal schistosomiasis and
      compared to controls from patients with malaria, Africans living in areas not
      endemic for these infections and healthy Germans. The investigation comprised the
      determination of the eosinophil granule proteins eosinophil cationic protein
      (ECP) and eosinophil-derived neurotoxin (EDN/EPX), and the neutrophil/monocyte
      granule protein myeloperoxidase (MPO). ECP and EDN/EPX levels were found elevated
      only in the three helminth infections that are associated with eosinophilia,
      while MPO was found elevated in all tested disease groups. The levels of
      eosinophil granule proteins observed in the helminth diseases by far exceeded
      those described for bronchial asthma and atopic dermatitis. ECP, EDN/EPX and MPO
      serum levels reflect the ongoing disease and are related to functional activity
      of the respective leukopoetic system. ECP and EDN/EPX appear to be markers of the
      eosinophil effector system and MPO a marker of the neutrophil and/or
      monocyte/macrophage effector system. Significantly higher ECP levels in chronic
      hyperreactive onchodermatitis (sowda) versus generalized onchocerciasis seem to
      reflect an augmented degree of antigenic stimulation, eosinophil activation and
      eosinophil turnover rates, indicating a more active mechanism of parasite
      clearance in sowda patients.

PMID- 9025986
TI  - Improved performance of the anion-exchange centrifugation technique for studies
      with human infective African trypanosomes.

PMID- 9025987
TI  - Mast cell apoptosis: from the DNA to the bedside.

PMID- 9025988
TI  - Growth and differentiation of eosinophils from human peripheral blood CD 34+
      cells.
AB  - Small numbers of CD34+ primitive hematopoietic progenitors are found in normal
      human peripheral blood. These cells differentiate to myeloid or lymphoid lineage
      under the influence of growth factors. We investigated the effects of IL5 and
      other growth factors on the production of eosinophils from peripheral blood CD34+
      cells. CD34+ cells were plated in agarose with different combinations of
      cytokines. At 14 days of growth a triple stain technique was used to identify
      eosinophil, monocyte and neutrophil colonies. IL5 alone did not support colony
      growth. In contrast GM-CSF and IL3 alone or together supported the generation of
      more than 50% eosinophil colonies. Addition of IL5 increased the fraction of
      eosinophil colonies to over 70%. Under the best conditions (IL3 + GM-CSF + IL5),
      the addition of interferon-a or LPS inhibited colony growth by 51% and 58%,
      respectively. Since IL5 alone did not support colony growth from CD34+ cells, we
      determined when IL5 responsive cells appeared in culture. Cells were grown
      initially with IL3 + GM-CSF, washed, and plated with IL5 alone. Only when
      progenitors were grown at least 3 days, could IL5 serve as the single growth
      factor supporting pure eosinophil colony growth (47 colonies/104 cells plated at
      day 3 and 134 colonies/104 cells at day 7). Growth of CD34+ in liquid culture for
      28 days in the presence of IL3, GM-CSF and IL5 resulted in almost 250 fold
      increase in cell number, yielding a population of 83% maturing eosinophils. We
      used our culture system and the sensitive technique of RT-PCR to analyze the
      kinetics of production of mRNA transcripts encoding several eosinophil proteins.
      Freshly isolated CD34+ cells contained no eosinophil granule protein transcripts
      and barely detectable amounts of some oxidase protein transcripts. At day 3 of
      culture no cells recognizable by histochemical staining as eosinophils could be
      detected, but transcripts for all five eosinophil granule proteins were present.
      These transcripts increased several fold during the entire culture period.
      Similar kinetics were seen for the NADPH oxidase protein transcripts. These
      studies demonstrate that within 3 days of culture, peripheral blood CD34+ cells
      can become committed to the eosinophil lineage as demonstrated by responsiveness
      to IL5 and production of specific protein transcripts.

PMID- 9025989
TI  - Flow cytometry analysis of malignant tumors of the head and neck--differences
      between two methods in the recognition of aneuploidy.
AB  - DNA aneuploidy, which reflects changes in nuclear DNA-content, as determined
      cytometrically is a candidate prognostic factor in squamous cell carcinoma of the
      head and neck. The aim of this study was to compare two different preparation
      methods with respect to their use in detecting aneuploid tumor cell populations
      in malignant tumors of the head and neck. Fresh frozen tumor material was used.
      The methods compared were a multistep procedure (A) including fixation of cells
      and enzymatic treatment, and a one step procedure (B). Both include RNAse and the
      use of propidium iodide for DNA staining. Forty-seven percent of the tumors were
      non-diploid according to method A, and 29% according to method B, discordant
      findings being made in 15 tumors, only two of which were non-SCC. Defining a
      'true non-diploid tumor' in this series as a tumor with a DNA index outside the
      range of diploidy detected either by method A or B, 59% (29/49) of the tumors
      were non-diploid. The sensitivity was 0.48 (14/29) for method B and 0.79 (23/29)
      for method A. The striking differences in accuracy between methods A and B
      emphasize the need of caution when new methods are introduced, and when results
      obtained with different methods are compared.

PMID- 9025990
TI  - A comparison of flow and image DNA cytometry in prediction of patient prognosis
      in surgically resected small cell lung cancer.
AB  - We have previously reported that flow cytometric tumor DNA content may be of
      prognostic significance in surgically resected small cell lung cancer (SCLC). We
      are particularly interested in determining prospective parameters for better
      selection of 'good prognosis' patients to proceed to surgery. Since flow
      cytometric measurements are poorly, if at all, applicable to endoscopic biopsy
      and cytology specimens we compared an image cytometric system to flow cytometry
      and clinical parameters in an extended series of surgically resected SCLC.
      Clinical follow-up was obtained on 75 patients having surgical resection for SCLC
      in the years 1981-92. Paraffin blocks were prepared for cytometry in standard
      fashion. Flow DNA histograms were characterised as diploid/tetraploid (n = 45) or
      DNA aneuploid (n = 27). DNA histograms obtained by image analysis were divided
      into type I (peridiploid n = 43) or type II (non-diploid with a minority of cells
      in peridiploid region; n = 31); 5c exceeding rate, 2c deviation index and
      malignancy grade were also computed. Overall two year survival was 27/75 patients
      (36%). Stage of disease was confirmed as a predictor of outcome with only 3/17
      (18%) N2 patients surviving for 2 years as compared to 24/52 (46%) patients with
      N0/N1 disease. Image cytometric histogram classification just reached statistical
      significance with type I histograms indicating a better prognosis (20/43
      survivors (47%) versus 7/31 (23%) patients with type II profiles, P < 0.05). Flow
      cytometry, 5cER, 2cD1 and malignancy grade were not useful in predicting
      prognosis. The results do not indicate a significant role for cytometry in SCLC.

PMID- 9025991
TI  - Immunohistochemical findings of arterial fibrinoid necrosis in major and lingual
      minor salivary glands of primary Sjogren's syndrome.
AB  - Arterial fibrinoid lesions in major salivary glands and lingual minor salivary
      glands from four autopsied patients with primary Sjogren's syndrome were studied
      histologically and immunohistochemically. On a morphological basis, the preceding
      arterial fibrinoid necrosis was regarded as medial damage, particularly of smooth
      muscle cells. The medial smooth muscle cells underwent vacuolated degeneration
      and disappeared, and resulted in full-blown fibrinoid arteritis. By means of the
      immunoperoxidase method the distribution of the immunoglobulins, fibrin,
      complement (C3), transferrin, ferritin, vimentin and lysozyme was studied. The
      normal arterial wall reacted with the lambda light chain of immunoglobulin,
      transferrin and vimentin Vacuolated degeneration of medial smooth muscle cells,
      regarded as the initial change in cases of vascular fibrinoid lesion, was
      positive for IgG, C3 and vimentin. We suggest that IgG antibody is a useful
      marker to detect the initial phase of arterial fibrinoid necrosis. In the foci of
      fibrinoid necrosis, fibrin, C3 and vimentin were detected. Among these three
      antibodies, only fibrin was negative in the normal arterial wall and vacuolated
      degenerates of medial smooth muscle cells. Mononuclear cells surrounding areas of
      fibrinoid necrosis stained strongly with antisera to immunoglobulins,
      transferrin, ferritin and vimentin, and negatively with fibrin, C3 and lysozyme
      antibodies.

PMID- 9025992
TI  - Does any correlation exist between the Gleason classification system and the
      computer-assisted microscope analysis of Feulgen-stained nuclei features in human
      prostate adenocarcinoma?
AB  - Grading prostatic adenocarcinomas remains an important problem. Various systems
      exist (including those proposed by Gleason) but none of these systems seems able
      to reliably predict either the lethal potential of a tumor in an individual
      patient or the responsiveness of an individual tumor to various forms of therapy.
      The most frequently used grading system, as proposed by Gleason, is essentially
      based on the description of tumor growth pattern. The aim of the present work is
      therefore to investigate whether the quantitative description of morphonuclear
      features (including cell anaplasia) and the DNA ploidy level can contribute
      significant information to the Gleason grading, thus partly at least reducing its
      subjective nature. This quantitative description was carried out by means of the
      Feulgen-stained nuclei image cytometry computation of 24 variables in 101
      prostatic adenocarcinomas. The results show that both DNA ploidy- and
      morphonuclear-related variables were weak discriminators for the various grades
      of the Gleason classification system, and particularly between the high (Gleason
      4 and 5) and the other Gleason-grades, i.e. the low (Gleason 1 and 2) and
      intermediate (Gleason 3) ones. The morphonuclear evidence of anaplasia is thus
      not redundant data on tumor growth pattern and may be expected to provide
      additional diagnostic information.

PMID- 9025993
TI  - Use of different histomorphometric parameters in the routine assessment of human
      skeletal muscle biopsies.
AB  - In the diagnosis of muscle biopsies it has become traditional to identify any
      changes in fibre size by measuring minimum fibre diameter (dmin), as past
      technical constraints prevented the routine measurement of other parameters. The
      advent of user-friendly computerised image analysis, however, has facilitated
      such measurements. We examined a total of 39 skeletal muscle biopsies, including
      normal, myopathic, myositic and neuropathic cases, to determine whether improved
      discrimination between normal and abnormal histology was now possible on the
      basis of fibre cross-sectional areas (CSA). Using a semi-automated image analysis
      system, measurements of dmin, CSA and fibre perimeter were made. In all case
      groups, the skew of the frequency distribution of area was greater than that of
      dmin, moreover the difference was more marked in the abnormal cases. As expected,
      the mean values of dmin and area were reduced in all abnormal cases. As expected,
      the mean values of dmin and area were reduced in all abnormal cases. The range of
      their values, however, was reduced in the myopathic and neuropathic cases and
      increased in the myositic cases. In conclusion, fibre area is a more valuable
      discriminator between normal and abnormal skeletal muscle than is dmin.

PMID- 9025994
TI  - Ultrastructural study of the keratinization of the dorsal epithelium of the
      tongue of Middendorff's bean goose, Anser fabalis middendorffii (Anseres,
      Antidae).
AB  - BACKGROUND: Comparative studies of ultrastructural features of tongues allow
      deductions to be made about relationships between structure and function, as
      reflected by an animal's feeding habits. The present study was performed to serve
      as a basis for further studies of avian feeding mechanisms and of relationships
      between the fine structure of the lingual epithelium and the development of the
      expression of keratins. METHODS: The light microscope, scanning electron
      microscope, and transmission electron microscope were used. RESULTS: The dorsal
      surface of the tongue of Middendorff's bean goose, Anser fabalis middendorffii,
      has a distinctive anterior region that extends for five-sixths of its length and
      has a clear posterior region. The anterior region, when observed macroscopically
      and by scanning electron microscopy, is distinguished along its forward half by a
      clear median line. The back half of the anterior region has an indistinct median
      sulcus in some parts. There are no lingual papillae on the entire dorsal surface
      of the anterior and posterior regions. Giant conical papillae are located in a
      transverse row between the anterior and posterior regions. On both lateral sides
      of the anterior region for five-sixths of the length of the tongue, lingual hairs
      are compactly distributed, and small numbers of large cylindrical papillae are
      arranged at almost regular intervals between these lingual hairs. Examination of
      the dorsal lingual epithelium by light and transmission electron microscopy
      provided histological and cytological criteria for distinguishing the anterior
      and posterior regions, both of which were composed of stratified squamous
      epithelium. Basal cells were similar throughout the dorsal epithelium. The
      intermediate layer of cells in the anterior region contained numerous tonofibrils
      in electron-dense bundles composed of tonofilaments of 10 nm in diameter. The
      outer layer was composed of electron-dense, well-keratinized cells, with layers
      of electron-lucent cells on the outermost surface. The cells in the intermediate
      layer in the posterior region of the tongue were almost completely filled with
      unbundled tonofilaments. The surface layer exhibited features of
      parakeratinization. In all of the giant conical papillae, the large cylindrical
      papillae, and the lingual hairs, the epithelium was strongly keratinized.
      CONCLUSIONS: The three-dimensional microanatomy and cytological features of the
      dorsal lingual epithelium of avians seem to be related to the functional role and
      shape of the tongue of each species in feeding.

PMID- 9025995
TI  - In vitro cell behavior of osteoblasts on Pyrost bone substitute.
AB  - BACKGROUND: Pyrost bone substitute has been shown to be a promising orthopedic
      biomaterial. However, little is known about mechanisms that are responsible for
      the genesis and development of the bond between bone and the Pyrost bone
      substitute. The purpose of this study is to elucidate the in vitro cell behavior
      of osteoblasts on Pyrost bone substitute. METHODS: By using primary culture of
      rat osteoblasts, the changes in cell morphology during adhesion and flattening
      onto the surface of Pyrost bone substitute were studied in vitro. At 1 hour, at 3
      hours, and at days 1, 3, and 7 after layering, the cell behavior was observed
      with scanning electron microscope. RESULTS: The processes of trypsinized
      osteoblast adhesion and spreading on Pyrost bone substitute consisted of 1)
      contact of rounded osteoblasts with the Pyrost substrate; 2) attachment of
      osteoblasts at point of contact; 3) centrifugal growth of filopodia; 4)
      flattening and spreading of the osteoblasts on the Pyrost substrate; 5) division
      and growth of osteoblasts; and 6) suspension of the osteoblasts across the pores
      by their processes. CONCLUSIONS: These results demonstrated that Pyrost can form
      a physico-chemical bond with osteoblasts. The Pyrost bone substitute not only
      supports osteoblasts attachment but also allows proliferation of the osteoblasts.

PMID- 9025996
TI  - Architectural and mechanical properties of the rat adductor longus: response to
      weight-lifting training.
AB  - BACKGROUND: The primary objective of this study was to determine the effects of
      an 8 week weight-lifting program on the mechanical, histochemical, and
      architectural properties of the rat adductor longus muscle, a predominantly slow
      adductor muscle. METHODS: The weight-lifting program was progressive such that
      the rats were performing three bouts of ten lifts with 300% body weight load
      every other day during the last 3 weeks of training. The in situ mechanical
      properties, fiber type composition, and architectural characteristics of the
      muscle were determined in control and weight-trained rats. Intramuscular
      electromyographic recordings were used to verify the recruitment of the adductor
      longus during the lifting task. RESULTS: The adductor longus was composed
      predominantly of slow fibers (approximately 80% slow oxidative) and had a
      relatively simple architectural design, i.e., one motor end-plate band near the
      center of the muscle, virtually no angle of pinnation of the fibers from the line
      of pull, and a fiber length:muscle length ratio of 0.72. The mean fiber type
      composition and fiber size, the total fiber number, and the mean physiological
      cross-sectional area of the adductor longus were similar in the two groups of
      rats. The mean body weight of weight-lifting rats was significantly less than
      control. The weight of the adductor longus relative to body weight and its
      fatigue resistance were higher and the maximum rate of shortening was slower in
      weight-lifting than in control rats. No other mechanical property was
      significantly affected by the training program. CONCLUSIONS: The results indicate
      that approximately 1 minute of over-load every other day by physiological
      recruitment of motor units can induce remodeling of the adductor longus of
      growing rats; i.e., the trained muscles were slower and less fatigable than
      control. Given that the effects on the architectural or force-generating
      properties of the muscles were small, the marked improvement in the ability to
      lift heavier loads as the training progressed appears to be more attributable to
      neurally related than to muscle-related phenomena.

PMID- 9025997
TI  - Effect of radiation on satellite cell activity and protein expression in
      overloaded mammalian skeletal muscle.
AB  - BACKGROUND: To gain insight into the role of satellite cells in skeletal muscle
      hypertrophy, the effect of radiation on small fiber formation, embryonic myosin
      heavy chain (embryonic MHC) production, and insulin-like growth factor I (IGF-I)
      production in overloaded adult rat soleus muscle was examined. METHODS: Adult rat
      soleus muscle was overloaded by ablation of the synergistic gastrocnemius,
      plantaris, and flexor digitorum profundus muscles of the right hindlimb. Half of
      the rats were subjected to gamma irradiation of the right hindlimb prior to
      ablation in an attempt to prevent satellite cell proliferation. RESULTS: Wet
      weight of the non-irradiated overloaded soleus muscle increased almost 40%
      compared to contralateral control muscle following 4 weeks of overload. Small
      fibers, which were rare in control muscle, accounted for 6.76 +/- 5.08% to 12.74
      +/- 7.76% of the total fiber number of the non-irradiated soleus following 1 to 4
      weeks of overload. Although usually absent in control muscle, IGF-I or embryonic
      MHC was immunolocalized in a small percentage (< 11%) of the mature fibers in the
      non-irradiated overloaded soleus. Irradiation prevented compensatory hypertrophy
      and nearly abolished small fiber formation in the overloaded soleus. However,
      irradiation did not diminish the percentage of mature fibers producing
      immunocytochemically detectable levels of embryonic MHC or IGF-I. CONCLUSIONS:
      Irradiation may prevent hypertrophy by impairing activation, proliferation,
      and/or differentiation of satellite cells. Small fibers in overloaded muscle
      appear to be new fibers arising from satellite cells. IGF-I may have a role in
      muscle hypertrophy involving satellite cell activation, or perhaps a more direct
      role that requires additional factors.

PMID- 9025998
TI  - Encapsulated sensory receptors within intraorbital skeletal muscles of a camel.
AB  - BACKGROUND: The occurrence of encapsulated sensory receptors in extrinsic ocular
      muscles differs among and within orders of mammals. Beyond indications that
      neuromuscular and neurotendinous spindles are present in extraocular muscles of
      the family Camilidae, little is known of their distributional characteristics. In
      fact there appear to be no distribution maps for any animal that show both major
      types of encapsulated muscle receptor in a full set of intraorbital skeletal
      muscles. METHOD: Serial histological sections of all skeletal muscles from one
      orbit of an adult, one-humped camel (Camelus dromedarius) were examined for
      encapsulated receptors. RESULTS: Encapsulated receptors were apparent in all the
      intraorbital skeletal muscles. Muscle spindles outnumbered tendon organs in the
      fleshy part of each muscle. For all muscles, spindles were most abundant in the
      half of the muscle near the origin; levator palpebrae superioris had a more even
      distribution of spindles along its length than did extraocular muscles. These
      longitudinal patterns of distribution for muscle spindles related in a general
      way to the nerve entry zone. Tendon organs occurred anywhere along a muscle's
      length, but they tended to be more frequent on either side of the major
      concentration of muscle spindles. Both types of encapsulated receptors were
      generally located nearer the perimeter than the center of cross sections through
      muscles. CONCLUSIONS: Encapsulated receptors of classic appearance are plentiful
      and have distinctive configurations within intraorbital skeletal muscles of the
      adult dromedary. When analyzed in conjunction with other studies, the present
      data give rise to testable explanations for the variability among genera in the
      number of encapsulated receptors in extraocular muscles.

PMID- 9026000
TI  - Revaluation on the types and pattern of distribution of sinusoidal fenestrations
      in the lobule of normal rat liver.
AB  - BACKGROUND: There is a need to identify the existence of large fenestrations and
      to evaluate the type and pattern of the distribution of sinusoidal fenestrations
      in the hepatic lobule. METHODS: The sinusoidal fenestrations in the rat liver
      lobule were investigated by scanning electron microscopy of perfusion-fixed
      specimens and by transmission electron microscopy of freeze-fracture replicas
      from immersion-fixed specimens. Ringer solution used for precleaning was
      equilibrated with 84%/16% O2/CO2 at 37 degrees C, and the perfusion pressure was
      maintained at 5-10 mmHg in the portal vein. RESULTS: The fenestrations were
      recognized on the luminal surface of sinusoids on the basis of regional
      difference in size and distribution within the lobule and divided into three
      types: small, medium-sized, and large. The small fenestrations were numerous in
      each region. The number of medium-sized fenestrations was large in the
      pericentral and intermediate regions, while that of large fenestrations was
      predominant in the intermediate region. Based on the occurrence of fenestrations,
      the sinusoids were also divided into three types. The type I sinusoid mainly
      showed small fenestrations and was predominant in the periportal region. The type
      II sinusoid showed small and medium-sized fenestrations and was predominant in
      the pericentral region. The type III sinusoid showed all the types of
      fenestrations including large ones and was predominant in the intermediate
      region. The images showing dumbbell-shaped or irregularly shaped margins were
      observed between small or medium-sized fenestrations on the freeze-fracture
      replica. CONCLUSIONS: 1) The fenestrations are divided into three types according
      to the size and pattern of distribution within the lobule. 2) The sinusoids are
      also divided into three types based on the distribution pattern of each type of
      fenestrations. 3) The small fenestrations are evenly distributed throughout the
      entire lobule, while the medium-sized and large fenestrations show the regional
      difference within the lobule. 4) The large fenestrations exist as real structures
      of the endothelial lining cells of sinusoids and may result from the fusion of
      contiguous smaller ones.

PMID- 9025999
TI  - Unusual nature and possible evolutionary implications of the male vesicular gland
      secretion in the tree shrew, Tupaia glis.
AB  - BACKGROUND: Whereas the secretion of the male vesicular gland in most mammals is
      amorphous, that of the tree shrew, Tupaia glis, was observed to be stored as
      globules. METHODS: Vesicular and prostate glands from Tupaia, fixed in
      glutaraldehyde and osmium, were studied in the light and electron microscopes.
      Other materials considered included the Tupaia ejaculate produced by
      electroejaculation and, for comparative purposes, sections of the vesicular gland
      from a dermopteran, the flying lemur. RESULTS: The vesicular gland epithelium in
      Tupaia secretes small granular aggregates and occasionally a denser aggregate
      that is associated with cells having obvious apical Golgi lamellae. In the
      alveolar lumen, these aggregates unite with others to form, respectively,
      granular and some dense globules of up to approximately 15 mu in diameter, which
      appear as such in semen produced by electroejaculation. In contrast to the
      prostate, however, precursor secretion vesicles were rare in the vesicular
      epithelium. Although poorly fixed, the vesicular gland secretion from a flying
      lemur also appeared to form globules. CONCLUSIONS: Although it is unlike the
      homogeneous secretion elaborated in most mammals, including primates and
      insectivores, the globular product of the Tupaia vesicular gland seems comparable
      to that in a variety of mega- and microbats, among representative species of
      which it appears to provide the bulk material for the vaginal copulation plug.
      Because a museum specimen examined here also indicates its occurrence in a flying
      lemur, the globular vesicular gland secretion common to Tupaiidae, to at least
      some Mega- and Microchiroptera, and apparently to Dermoptera may provide a soft
      tissue feature of some value in the cladistic approach to phylogenetic
      reconstruction within the Archonta. Anat.

PMID- 9026001
TI  - Ultrastructural and immunocytochemical study of the pulmonary intravascular
      macrophages of Escherichia coli lipopolysaccharide-treated sheep.
AB  - BACKGROUND: Pulmonary intravascular macrophages (PIMs) of sheep, cattle, goats,
      and horses have a novel heparin-sensitive chain of globules, called a surface
      coat, on their plasma membrane. The globules are arranged at a distance of 32-39
      nm from the plasma membrane of PIMs. Intravascular nonbiological tracer particles
      complex with these globules prior to their endocytosis by the PIMs. METHODS: We
      conducted a preliminary in vivo time-course study in sheep to investigate
      responses of the coat globules to a single dose of Escherichia coli
      lipopolysaccharide (E. coli LPS). Six sheep (6-9 months of age) were used in this
      study, and five of them were intravenously injected with E. coli (1 microgram/kg
      body weight) and euthanised at 3, 8, 10, 30, and 180 min (n = 1 each) after
      treatment. One sheep injected with saline solution served as the control. Acid
      phosphatase (AcPase) cytochemistry and immunocytochemistry using a polyclonal
      antibody were employed to localize secretory activity and E. coli LPS
      respectively in the PIMs. RESULTS: The surface coat of PIMs disappeared rapidly
      following the LPS administration. Escherichia coli LPS micelles and coat globules
      were colocalized as a complex in the endosomes of PIMs. At 8-10 min following the
      treatment, endosomal and the other membranes were disrupted, and the LPS was
      identified in cytoplasm and nuclear matrix of PIMs simultaneously with the
      development of pulmonary interstitial edema. Progression of AcPase reactivity
      along the nucleus-Golgi complex axis coupled with intense buildup of coated
      transport vesicles within 30 min of the LPS injection suggested enhanced
      biosynthetic activity in the PIMs. CONCLUSIONS: This study provides initial data
      on the sensitivity of the coat globules and their possible role in the
      endocytosis of E. coli LPS by the PIMs. Rapid biosynthetic activation of PIMs
      concurrent with loss of the coat and treatment with the LPS probably results in
      the secretion of inflammatory substances and contributes to the enhanced
      susceptibility of sheep to endotoxin-induced lung pathology.

PMID- 9026002
TI  - Histological, histochemical, and fine structural observations on the lymph node
      of the common seal (Phoca vitulina) and the grey seal (Halichoerus grypus).
AB  - BACKGROUND: The recent seal death epizootic prompted interest in their immune
      system, for which no current morphological data were available. METHODS: Lymph
      nodes from adult harbor seals (Phoca vitulina) and grey seals (Halichoerus
      grypus) were investigated by light microscopy, electron microscopy, and lectin
      histochemistry. RESULTS: No significant differences in the lymph node morphology
      were found between the two species, and the overall organization of the nodes
      comprises of capsule, trabeculae, cortex, paracortex, and medulla. Capsule and
      trabeculae are composed of tightly packed collagen and elastic fibrils and are
      rich in fibroblasts, myofibroblasts, and smooth muscle cells. Unmyelinated nerve
      fibers are common. The cortex contains numerous secondary follicles with well
      developed germinal centers and paracortical areas with high endothelial venules.
      Antigen-presenting cells and phagocytic macrophages were abundantly present. The
      medullary cords contain numerous plasma cells. Fibroblastic reticulum cells are
      common throughout the parenchyma and transverse the sinus. Marginal, radial, and
      medullary sinuses are lined by littoral cells. The visceral lining of the sinuses
      is marked by macrophages and by numerous mast cells. CONCLUSIONS: The morphology
      of seal lymph nodes does not differ significantly from that of terrestrial
      mammals. Earlier functional conclusions concerning seal lymph nodes are
      substantiated by this morphological study.

PMID- 9026003
TI  - Cell proliferation is reduced in parthenogenetic mouse embryos at the blastocyst
      stage: a quantitative study.
AB  - BACKGROUND: Parthenogenetic and androgenetic embryos fail to develop to term,
      possibly because of genomic imprinting, an epigenetic alteration of certain
      genes, depending on the parent of origin. The effect of this phenomenon has been
      studied mainly in mid-gestation embryos, without morphological abnormalities
      detected during the preim-plantation period. Nevertheless, parthenogenetic mouse
      embryos never develop to the blastocyst stage in the same numbers as do
      fertilized ones, and up to 50% fail to implant, suggesting that genomic
      imprinting may be responsible for this lack of viability. METHODS: We have made a
      quantitative and morphometric analysis of the cell proliferation capacity at the
      end of the preimplantation period in parthenogenetic mice to study if such
      parameter is affected by the monoparental constitution of the embryos. RESULTS
      AND CONCLUSIONS: We have found that, apart from the different morphology and cell
      number induced by culture conditions, parthenogenetic mouse blastocysts have a
      significantly smaller cell number than do fertilized control embryos. Our
      interpretation of these results is that the monoparental constitution of these
      embryos may be responsible for the lack of some factor required to sustain cell
      proliferation after the morula stage.

PMID- 9026004
TI  - Immunocytochemical changes in the fetal pancreatic islet following fetal
      administration of streptozotocin in the rat.
AB  - BACKGROUND: Streptozotocin (STZ) is selectively toxic to the B cells in the
      pancreatic islets. It is well known that in the adult rat, STZ causes the death
      of B cells, and it eventually induces diabetes mellitus. The present study was
      conducted to detect what morphological changes could be induced in the fetal B
      cells following a direct injection of STZ into the fetus in utero during late
      pregnancy in the rat. METHODS: STZ (400 micrograms/g body weight) was injected
      into the fetus in utero at 10:00 on day 19 of gestation. Three, 6, 24, and 48 hr
      after injection, the changes in the B cells (anti-insulin serum positive cells)
      were examined immunohistochemically. The total volume of the B cells was
      measured. Electron microscopic observation was made as well. RESULTS: Six hr
      after STZ injection, some B cells were destroyed so that their granules were
      distorted and burst. Twenty-four hr after STZ injection, a large majority of the
      existing B cells were disintegrated, and a number of small isletlike clusters of
      immature cells appeared among the exocrine acini. The total volume of anti
      insulin serum positive cells was strikingly decreased. At 48 hr after injection,
      however, the volume returned to a level that was comparable to that of their
      littermate controls. CONCLUSIONS: The regeneration of the B cells may occur
      because of the high cell proliferative activity of undifferentiated cells
      following the destruction of the B cells caused by an injection of STZ.

PMID- 9026005
TI  - Lingual papillae of the growing rat as a model of vasculogenesis.
AB  - BACKGROUND: Capillary sprouting is an important mechanism that initiates
      neovascularization. Because observation of capillary sprouting and its
      morphological staging can be problematic, we sought to establish a simple model
      of capillary growth. METHODS: Rats were obtained at gestational days 15, 16, and
      20, at birth, and at postnatal day 10. Scanning electron microscopy (SEM) of
      vascular casts, freeze-fractured and epithelium-exfoliated specimens, as well as
      transmission electron microscopy (TEM) of tissue sections were used. RESULTS: In
      day 15 fetuses, the filiform papillae and their connective tissue cores had not
      been formed, but a simple capillary network without regional differences was
      present. In day 16 fetuses, mesenchymal cells started to form papillary
      connective tissue cores, and, inside the epithelium, ridges were found. Capillary
      sprouts arose from the preexisting sinusoidal capillaries by elongation and
      widening, invaded into connective tissue cores in day 20 fetuses, and gradually
      bifurcated to form capillary loops in the prospective giant conical papillae of
      the newborn rat. In postnatal day 10 rats, the capillary network beneath the
      papillae became bilayered. CONCLUSION: Vascular formation in the lingual papillae
      in growing rats offers an easy model for the observation of capillary sprouting.
      In this model, the sprouts arise from preexisting sinusoidal capillaries and not
      from veins, as usually observed in other models. The mechanism of capillary
      growth is the elongation of (preexisting) sinusoidal capillaries into the
      developing connective tissue cores and toward the forming epithelial ridges.

PMID- 9026006
TI  - Morphology and electrophysiology of guinea-pig paratracheal neurones.
AB  - BACKGROUND: Although guinea-pig tracheal preparations are used as models of
      asthma, the morphological and electrophysiological characteristics of its
      associated ganglion neurones (paratracheal neurones) have not been characterized.
      METHODS: Intracellular staining and electrophysiological recording techniques
      have been applied to guinea-pig paratracheal neurones in isolated preparations.
      RESULTS: Most (32/35) neurones were multipolar, with many short (< 70 microns),
      finely tapering processes and one or more long processes; the latter, which were
      traced for up to 400 microns, travelled along the interconnecting nerve trunks,
      often in pairs, or over smooth muscle bundles. About 20% (6/32) of neurones had
      conspicuous somal extensions that gave rise to 3-8 processes. The soma morphology
      of neurones of the intrinsic ganglionated plexus close to the trachealis muscle
      were usually more complex than those in or associated with recurrent or vagal
      nerve trunks. Two types of neurone were identified electrophysiologically;
      neurones with fast excitatory synaptic potentials were found only in ganglia
      located very close to the smooth muscle, whereas > 90% of neurones lacking
      synaptic inputs were associated with recurrent nerve trunks. Transmural or focal
      electrical stimulation failed to evoke either slow inhibitory or slow excitatory
      (cholinergic or non-cholinergic) synaptic potentials in either
      electrophysiological type. CONCLUSIONS: It is tentatively concluded that the
      neurones of the intrinsic ganglionated plexus receiving synaptic input probably
      provided the para-sympathetic innervation to effector cells (such as trachealis
      muscle). Both these and the spiking neurones located in or near nerve trunks
      showed little potential for synaptic modulation of their excitability.

PMID- 9026007
TI  - Morphometric analysis of the human vestibular nuclei.
AB  - BACKGROUND: Cytoarchitectural investigations of the vestibular nuclei have been
      undertaken in different species of mammals. These data provide a description of
      the general architecture of the nuclei but limited information about quantitative
      characteristics of their cell population. We have recently obtained data about
      the morphometric parameters of the vestibular nuclei neurons in some species. The
      application of quantitative image analysis techniques to the research of the
      cellular morphology in the vestibular area of humans might provide basic
      information to compare with data from animal studies, taking into account the
      observed correlation between physiological and morphological properties of
      vestibular neurons. METHODS: The characteristics of the major vestibular nuclei
      in humans have been studied with light microscopic techniques in serially cut
      sections. Camera lucida drawings of the vestibular nuclei and their neurons were
      made and subjected to computerized image analysis. For each vestibular nucleus,
      information was obtained about topography, morphological characteristics (i.e.,
      location, volume, and length), and the number and morphometric parameters of
      their neurons (cross-sectional areas, maximum and minimum diameters).
      Morphometric data about cell parameters were statistically analyzed by comparing
      the populations within different parts of each nucleus and from different nuclei.
      RESULTS: Among the vestibular nuclei, the medial, which is the largest, has the
      greatest number of neurons, and the interstitial, the least. The lateral and
      interstitial nuclei contain the largest cells, and the descending nucleus has the
      smallest cells. The superior nucleus contains cells of intermediate size. The
      size of cells decreases in a rostrocaudal direction in the medial, lateral, and
      descending nuclei, the opposite trend being observed in the superior nucleus.
      Within the superior and medial nuclei, there are discrete areas with cells with
      distinctive characteristics. CONCLUSIONS: These results suggest that, just as
      most of the anatomical characteristics of the second-order neurons found in
      animals have been preserved in humans, so the physiological mechanisms observed
      in the vestibular system of animals should apply to humans.

PMID- 9026008
TI  - Gross and microscopic anatomy of the human intrinsic cardiac nervous system.
AB  - BACKGROUND: The extent and locations of intrinsic cardiac ganglia on the human
      heart were investigated to facilitate studying their function. METHODS: The
      locations and number of major intrinsic cardiac ganglia were determined in six
      human hearts by means of microdissection following methylene blue staining. Light
      and electron microscopic analyses were performed on right atrial and cranial
      medial ventricular ganglia obtained from 12 other human hearts. RESULTS: Gross
      anatomy: Collections of ganglia associated with nerves, i.e., ganglionated
      plexuses, were observed consistently in five atrial and five ventricular regions.
      Occasional ganglia were located in other atrial and ventricular regions. Atrial
      ganglionated plexuses were identified on 1) the superior surface of the right
      atrium, 2) the superior surface of the left atrium, 3) the posterior surface of
      the right atrium, 4) the posterior medial surface of the left atrium (the latter
      two fuse medially where they extend anteriorly into the interatrial septum), and
      5) the inferior and lateral aspect of the posterior left atrium. Ventricular
      ganglionated plexuses were located in fat 1) surrounding the aortic root, 2) at
      the origins of the right and left coronary arteries (the latter extending to the
      origins of the left anterior descending and circumflex coronary arteries), 3) at
      the origin of the posterior descending coronary artery, 4) adjacent to the origin
      of the right acute marginal coronary artery, and 5) at the origin of the left
      obtuse marginal coronary artery. Microscopic anatomy: Ganglia ranged in size from
      those containing a few neurons to large ganglia measuring up to 0.5 x 1 mm. The
      human heart is estimated to contain more than 14,000 neurons. Neuronal somata
      varied in size and shape. Many axon terminals in intrinsic cardiac ganglia
      contained large numbers of small, clear, round vesicles that formed asymmetrical
      axodendritic synapses, whereas a few axons contained large, dense-cored vesicles.
      CONCLUSIONS: The human intrinsic cardiac nervous system is distributed more
      extensively than was considered previously, most of its ganglia being located on
      the posterior surfaces of the atria and superior aspect of the ventricles. Each
      ganglion therein contains a variety of neurons that are associated with complex
      synaptology.

PMID- 9026028
TI  - Comb-type polycations effectively stabilize DNA triplex.
AB  - DNA triplex formation has been studied as a potential strategy for regulation of
      gene expression. The triplex is, however, unstable under physiological
      conditions, so that an effective stabilizer for the triplex formation is needed.
      Here is shown a novel strategy to stabilize the triplex based on the molecular
      design of a comb-type polycation. Linear polycations, such as poly(L-lysine) and
      poly(L-arginine), thermally stabilize DNA duplexes (and triplexes). The complexes
      between DNA and the polycation are irreversible and are liable to precipitate out
      of aqueous media. The irreversibility and phase separating properties of the
      complex impede association of single-stranded (ss) DNAs in the complex to form
      duplexes and triplexes. A comb-type polycation consisting of a poly(L-lysine)
      backbone and grafted chains of hydrophilic polymers was prepared. The comb-type
      copolymers increased solubility of their complex with DNA and suppressed
      conformational changes of DNA. Thermal melting curve analyses revealed that the
      comb-type copolymer markedly stabilized DNA triplexes and did not disturb ssDNAs
      in forming duplexes and triplexes. Reversible and one-step melting/reassociation
      transitions of poly(dA).2poly(dT) triplex were shown in the pressure of the
      copolymers. The stabilizing effect of the copolymer was larger than that of
      spermine, a polyamine considered effective in stabilizing triplexes. These
      results indicated that molecular design of polycations with a comb-type structure
      is a novel strategy to create efficient triplex stabilizers. Such comb-type
      copolymer consisting of various types of polycation backbones and hydrophilic
      graft chains may have many applications in which specific and precise
      interactions of polynucleotides are involved.

PMID- 9026029
TI  - Synthesis of a novel [125I]neonicotinoid photoaffinity probe for the Drosophila
      nicotinic acetylcholine receptor.
AB  - The insect nicotinic acetylcholine receptor (nAChR) is the target for the major
      insecticide imidacloprid (IMI) and for the first candidate photoaffinity probe
      described here. Addition to 1-[(6-chloro-3-pyridinyl) methyl]-4,5-dihydro-2
      nitromethylene-1H-imidazolidine (the nitromethylene analog of the nitroimine IMI)
      of formaldehyde and any one of several primary amines is known to give hexahydro
      8-nitroimidazo[1,2-c]pyrimidine derivatives. These imidazopyrimidines with a wide
      range of N-substituents were found to inhibit [3H]IMI binding to the Drosophila
      or Musca nAChR by 50% (IC50) at 0.7-38 nM. Esterification of the N-(2
      hydroxyethyl) derivative with 2-azido-5-(trimethylstannyl)-benzoic acid and then
      iododestannylation using Na125I and chloramine-T provide the candidate
      photoaffinity probe 6-[2-(2-azido-5-[125I]iodobenzoyl) ethyl]-1-[(6-chloro-3
      pyridinyl)methyl]-1,2,3,5,6,7-hexahydro-8 -nitroimidazo[1,2-c]pyrimidine. This
      compound (unlabeled) has an IC50 of 8 nM for [3H]-IMI binding in Drosophila head
      membranes, and the 125I-labeled photoaffinity probe labels only a 66 kDa
      protein(s) at a specific site inhibited by (-)-nicotine, consistent with the
      insecticide-binding subunit of the nAChR.

PMID- 9026030
TI  - Conjugates of oligonucleotides with triplex-specific intercalating agents.
      Stabilization of triple-helical DNA in the promoter region of the gene for the
      alpha-subunit of interleukin 2 (IL-2R alpha).
AB  - The stabilization of triple-helical DNA under physiological conditions is an
      important goal for the control of gene expression using the antigen strategy, an
      approach whereby an oligonucleotide binds to the major groove of double-helical
      DNA to fom a triple helix. To this end, triplex-specific intercalators, namely
      benzopyridoindole (BPI) and benzopyridoquinoxaline (BPQ) derivatives, have been
      conjugated to the 5' end or to an internucleotide position of a 15-mer
      oligonucleotide. These conjugates were then tested, using thermal denaturation
      experiments, for their ability to form and stabilize a triple-helical structure
      involving a 42-mer duplex target. All of the conjugates were found to do so. The
      B[h]PQ derivatives stabilized particularly well when attached to the 5' end with
      a delta Tm of 15 degrees C and -delta delta G degrees 37 of 3.4 kcal mol-1 (pH
      6.9, 140 mM KCI, 15 mM sodium cacodylate, 2 mM MgCl2, 0.8 mM spermine). Though
      most of the derivatives when attached to the internucleotide position were not
      able to stabilize triple-helical DNA as well as when attached to the 5' end, one
      B[f]PQ derivative with an internucleotide attachment did so, with a delta Tm of
      13 degrees C and -delta delta G degrees 37 of 2.8 kcal mol-1. To a lesser degree,
      these conjugates were also able to stabilize duplex structures with single
      stranded targets. Results were compared to the stabilization obtained with
      acridine conjugates as well as to a similar study performed with a different
      sequence.

PMID- 9026031
TI  - Surface modification of hemoglobin vesicles with poly(ethylene glycol) and
      effects on aggregation, viscosity, and blood flow during 90% exchange transfusion
      in anesthetized rats.
AB  - Poly(ethylene glycol) (PEG5000)-conjugated phosphatidylethanolamine was
      introduced onto the surface of hemoglobin vesicles (HbV); phospholipid vesicles
      encapsulating concentrated Hb (d = 0.257 +/- 0.087 micron; P50 = 32 Torr). The
      obtained PEG-modified HbV (HbV-PEG) was studied for use as a red cell substitute
      from the viewpoint of rheology, surface properties, and hemodynamics. The
      viscosity of the unmodified HbV suspended in saline ([Hb] = 10 g/dL) was 2.6 cP
      (shear rate = 358 s-1, 37 degrees C), less than that of human blood (4 cP).
      However, when suspended in a 5 g/dL albumin solution (HbV/ albumin), it increased
      to 8 cP due to the molecular interaction between albumin and vesicles, and the
      viscosity increased with decreasing shear rate, e.g., 37 cP at 0.58 s-1. As for
      the HbV-PEG/albumin, on the other hand, the viscosity was 3.5 cP at 358 s-1 and
      was comparable with that of human blood. Optical microscopy showed formless
      flocculated aggregates of the unmodified HbV, while no aggregates were confirmed
      for the HbV-PEG. The steric hindrance of PEG chains seemed to be effective in
      preventing intervesicular access and the resulting aggregation. To estimate the
      flow profiles in the capillaries, the suspensions were allowed to penetrate
      through isopore membrane filters (pore size = 0.4-8 microns, cf. capillary
      diameter = 4-10 microns). The penetration rate of the HbV-PEG/albumin was higher
      than that of the unmodified HbV/albumin due to the suppression of aggregation,
      whereas both of them were significantly higher than that of human blood due to
      the smaller size of vesicles than RBC. Ninety percent exchange transfusion was
      performed with the HbV-PEG/albumin or HbV/albumin in anesthetized Wistar rats (n
      = 6). The blood flow in the abdominal aorta increased 1.5 times, and the total
      peripheral resistance decreased in the HbV-PEG/albumin-administered group in
      comparison with the HbV/albumin group. As for the blood gas parameters, the base
      excess and pH remained at higher levels in the HbV-PEG/albumin group, and the O2
      tension in mixed venous blood for the HbV-PEG/albumin group tended to be
      maintained at a higher level than that for the HbV/albumin group. Thus, the PEG
      modification of HbV reduced the viscosity by the suppression of aggregation and
      resulted in prompt blood circulation in vivo.

PMID- 9026032
TI  - Electrochemistry of methylene blue bound to a DNA-modified electrode.
AB  - Gold surfaces have been derivatized with 15-base-pair double-stranded DNA
      oligonucleotides containing a pendant 5' hexanethiol linker. The electrochemistry
      of intercalated methylene blue has been investigated at these modified
      electrodes. Chronocoulometry, cyclic voltammetry, ellipsometry, and quantitation
      via 32P labeling are all consistent with a surface coverage of > or = 75% with
      the DNA helices stacked at an angle from the electrode surface. Cyclic
      voltammetry at low methylene blue/ duplex stoichiometries yields well-behaved
      surface waves with E degrees = -0.25 V (vs SCE), a value 0.03 V negative of that
      in aqueous solution. A binding isotherm for methylene blue at an electrode
      derivatized with the double-stranded sequence 5' SH-(CH2)6-p-AGTACAGTCATCGCG 3'
      was obtained from coulometric titrations and gave an affinity constant equal to
      3.8(5) x 10(6) M-1 with a saturation value of 1.4(2) methylene blue intercalators
      per DNA duplex. Taken together, these experiments support a model for the surface
      morphology in which DNA duplexes are densely packed; methylene blue therefore
      reversibly binds to sites in the DNA that are close to the bulk solution.
      Electrochemistry at DNA-derivatized electrodes provides a valuable methodology to
      examine DNA-bound redox reactions and may offer new insight into DNA-mediated
      electron transfers.

PMID- 9026033
TI  - Influence of endosome-destabilizing peptides on efficacy of anti-HIV
      immunotoxins.
AB  - The effects on immunotoxin efficacy of fusogenic peptides derived from influenza
      virus hemagglutinin have been studied. These peptides have an amphipathic nature
      and change conformation from random at pH 7 to helical at pH 5. Fusogenic
      peptides are reported to destabilize endosomal membranes, resulting in the
      release of contents into the cytoplasm. The use of two related fusogenic peptides
      to enhance the efficacy of anti-HIV immunotoxins is described. The direct
      toxicity of the peptides was tested on HIV-infected H9/NL4-3 cells. Peptide HA24
      was considerably more toxic than HA23. The peptides were mixed with two different
      immunotoxins. Immunotoxin action was enhanced by both peptides, with HA24
      providing greater enhancement than HA23. Immunotoxins were then constructed by
      coupling HA23 or HA24 to the targeting antibody with disulfide-containing
      linkers. Peptide HA23 enhanced the activity of the immunotoxin 4-5-fold.
      Surprisingly, HA24 significantly inhibited immunotoxin activity. Coupling the
      peptides to the immunotoxin had no effect on antigen binding characteristics or
      the activity of the toxic moiety. Bafilomycin A1, an agent that inhibits vacuolar
      acidification, markedly potentiated the effects of all immunotoxins. These
      results demonstrate that amphipathic peptides can influence the efficacy of
      immunotoxins, but in sometimes unpredictable ways.

PMID- 9026034
TI  - Synthesis of the protein cutting reagent iron (S)-1-(p
      bromoacetamidobenzyl)ethylenediaminetetraacetate and conjugation to cysteine side
      chains.
AB  - Convenient methodology for preparation and conjugation of the protein-cutting
      iron chelate iron (S)-1-(p-bromoacetamidobenzyl) ethylenediaminetetraacetate (Fe
      BABE) is given. This formulation of the reagent can be handled in a manner
      analogous to many other protein-labeling reagents, such as fluorescent probes or
      cross-linkers. By taking advantage of the recently discovered peptide hydrolysis
      reaction, the chelate may be tethered to a single site (e.g., a cysteine side
      chain) and used to map its proximity to individual peptide bonds by automated
      Edman sequencing of the protein fragments produced. The method is illustrated by
      conjugation of Fe-BABE to the carboxy terminal domain (amino acid residues 234
      329) of the Escherichia coli RNA polymerase alpha subunit. The molecular mass of
      the protein conjugate was confirmed by electrospray ionization mass spectrometry.

PMID- 9026035
TI  - Site-specific photomodification of DNA by porphyrin-oligonucleotide conjugates
      synthesized via a solid phase H-phosphonate approach.
AB  - meso-Tris(4-pyridyl)[[(omega-hydroxyhexamethylene)carbamoyl]phenyl ] porphyrin
      was converted to its H-phosphonate derivative and conjugated using solid phase
      synthesis with the 5'-hydroxyl group of deoxyribonucleotides d(TCTTCCCA) and
      d(T)12. These conjugates were transformed into their (N
      methylpyridiniumyl)porphyrin analogs in the reaction with methyl iodide. A 532 nm
      laser beam was utilized to photoactivate both types of the conjugates in the
      presence of the target 22-mer and 16-mer oligonucleotides. Photoactivation of
      porphyrin-oligonucleotide conjugates resulted in site-specific DNA modification
      characterized by a main reaction site size of approximately 5 bases.

PMID- 9026036
TI  - Dioleoylmelittin as a novel serum-insensitive reagent for efficient transfection
      of mammalian cells.
AB  - Amphipathic peptides can be useful effectors to enhance gene delivery. However,
      peptide/DNA complexes usually require additional effectors, such as fusogenic
      lipids, to mediate efficient transfection. Due to weak and/or multiple
      interactions between the various components of the system, the transfecting
      complexes are often heterogeneous and unstable in biological fluids. Accordingly,
      a hybrid molecule resulting from the covalent coupling of an amphipathic,
      membrane-disturbing peptide to a lipid moiety might create a stable and efficient
      peptide-based gene transfer system. The present work describes such a novel
      hybrid molecule, dioleoylmelittin, resulting from the conjugation of
      dioleoylphosphatidylethanolamine-N-[3-(2-pyridyldithio)propionate] with
      [Cys1]melittin. Dioleoylmelittin had a lower hemolytic and membrane-disturbing
      activity than melittin. Size and zeta potential measurements, DNA gel
      electrophoresis, and electron microscopy showed that dioleoylmelittin, unlike
      melittin, was able to complex plasmid DNA to form spherical particles with a net
      positive charge and a diameter between 50 and 250 nm. These particles, prepared
      at an optimal 10/1 dioleoylmelittin/DNA ratio (w/w), mediated efficient transient
      transfection of reporter genes in cultured mammalian cells including primary
      cells. The luciferase activity induced by the dioleoylmelittin/DNA complex was 5
      500-fold higher than that induced by a cationic lipid/DNA complex, depending on
      the cationic lipid and the cell-line. Surprisingly, the presence of 10-50% fetal
      calf serum during dioleoylmelittin-mediated transfection enhanced 1.5-3-fold gene
      expression. Dioleoylmelittin represents a new class of efficient peptide-based
      transfection reagents, especially suited for serum-sensitive cells.

PMID- 9026037
TI  - Optimization of conditions for formation and analysis of anti-CD19 FVS191 single
      chain Fv homodimer (scFv')2.
AB  - In this report, we present the production of a dimeric form of anti-CD19 scFv,
      the FVS191cys (scFv')2. Anti-CD19 scFv FVS191cys was constructed by engineering a
      cysteine residue at the C terminus of the V1, domain of scFv FVS191. FVS191cys
      (scFv')2 was formed through a disulfide bond between two FVS191cys molecules. To
      optimize the yield of FVS191cys (scFv')2, the effects of oxidation time, buffer
      pH, and temperature on the formation of dimeric scFv were analyzed. Our study
      indicates that the formation of FVS191cys (scFv')2 is oxidation time- and buffer
      pH-dependent; a high pH buffer facilitates the formation of disulfide-linked
      (scFv')2. The maximum yield of FVS191cys (scFv')2 can be achieved when FVS191cys
      is air-oxidized at 4 degrees C, in buffer with a pH of 8.5-9. The biological
      activity of FVS191cys (scFv')2 was analyzed by ELISA and an internalization
      assay. FVS191cys (scFv')2 has a CD19 binding ability similar to that of its
      parental mAb B43 and is internalized by CD19 positive Nalm 6 cells. This study
      indicates that FVS191cys (scFv')2 is a potential candidate for tumor diagnosis or
      therapy.

PMID- 9026038
TI  - Influence of coupling method on the luminescence properties, coupling efficiency,
      and binding affinity of antibodies labeled with europium (III) chelates.
AB  - A series of chelating 4-(phenylethynyl)pyridines having various 1,3,5-triazin-2
      ylamino groups at the para position of the phenyl ring was synthesized. Their
      europium chelates were coupled to antibodies and the properties of antibody
      conjugates analyzed by fluorometry and in time-resolved fluorometric immunoassay.
      The substituents in the triazine ring were observed to have various effects on
      the chelate luminescence, the labeling properties of the chelates, and the
      immunoreactivity of labeled antibodies. The series of substituted triazinyl
      derivatives serves as a model of bioreactive groups that can be applied when
      certain properties are searched for, such as improved chelate solubilities,
      minimized internal quenching, different effects on the ligand triplet state, and
      stipulated coupling reactivities.

PMID- 9026039
TI  - Chromogenic lactate-leukocyte esterase substrates.
AB  - The first successful reported use of lactate-based chromogenic, colorimetric
      substrates for a serine protease-based enzyme is described. A series of hydroxy
      protected 5-phenyl-3-hydroxypyrrolyl L-lactate substrates of the general formula
      RO-Lac-OPP were prepared and formulated into reagents for the determination of
      leukocytes in dry phase formats.

PMID- 9026040
TI  - Peptide-mediated gene delivery: influence of peptide structure on gene
      expression.
AB  - Cationic peptides possessing a single cysteine, tryptophan, and lysine repeat
      were synthesized to define the minimal peptide length needed to mediate transient
      gene expression in mammalian cells. The N-terminal cysteine in each peptide was
      either alkylated or oxidatively dimerized to produce peptides possessing lysine
      chains of 3, 6, 8, 13, 16, 18, 26, and 36 residues. Each synthetic peptide was
      studied for its ability to condense plasmid DNA and compared to polylysine19 and
      cationic lipids to establish relative in vitro gene transfer efficiency in HepG2
      and COS7 cells. Peptides with lysine repeats of 13 or more bound DNA tightly and
      produced condensates that decreased in mean diameter from 231 to 53 nm as lysine
      chain length increased. In contrast, peptides possessing 8 or fewer lysine
      residues were similar to polylysine19, which bound DNA weakly and produced large
      (0.7-3 microns) DNA condensates. The luciferase expression was elevated 1000-fold
      after HepG2 cells were transfected with DNA condensates prepared with alkylated
      Cys-Trp-Lys18 (AlkCWK18) versus polylysine19. The gene transfer efficiencies of
      AlkCWK18 and cationic lipids were equivalent in HepG2 cells but different by 10
      fold in COS 7 cells. A 40-fold reduction in particle size and a 1000-fold
      amplification in transfection efficiency for AlkCWK18 DNA condensates relative to
      polylysine19 DNA condensates suggest a contribution from tryptophan that leads to
      enhanced gene transfer properties for AlkCWK18. Tryptophan-containing cationic
      peptides result in the formation of small DNA condensates that mediate efficient
      nonspecific gene transfer in mammalian cells. Due to their low toxicity, these
      peptides may find utility as carriers for nonspecific gene delivery or may be
      developed further as low molecular weight DNA condensing agents used in targeted
      gene delivery systems.

PMID- 9026041
TI  - Characterization of oligodeoxyribonucleotide-polyethylene glycol conjugates by
      electrospray mass spectrometry.
AB  - Electrospray mass spectrometry (ESMS) was used to characterize a number of
      differently functionalized polyethylene glycol-oligodeoxyribonucleotide
      conjugates. Sample preparation was found to be crucial to obtaining quality data.
      The resolution and precision of ESMS allowed for the identification of individual
      conjugates differing in MW by a single ethylene glycol unit with an accuracy of <
      or = 1 (0.02% of the molecular weight). In addition, ESMS was shown to be
      valuable in identifying chromatographically unresolvable components of a
      derivatized polyethylene glycol-oligonucleotide conjugate mixture.

PMID- 9026043
TI  - Educating the nation's physicians about family violence and abuse.

PMID- 9026042
TI  - Determination of the extent of protein biotinylation by fluorescence binding
      assay.
AB  - A method was developed to determine the total amount of biotin present in
      biotinylated protein conjugates. Conjugates of bovine serum albumin, alkaline
      phosphatase, and horseradish peroxidase were used in this case study. The extent
      of biotinylation was determined by complete acid hydrolysis or by enzymatic
      digestion using proteinase K to release biotin from the biotinylated proteins,
      followed by sensitive detection of biotin using a coupled HPLC-binding assay
      system. This detection system is based on the enhancement of the fluorescence of
      streptavidin-FITC by biotin. The extent of biotinylation determined by this
      method was compared with the values obtained by a conventional colorimetric
      method that is based on the displacement of the dye 4-hydroxyazobenzene-2
      carboxylic acid (HABA) from the binding sites of avidin. It was found that,
      because the described method determines the amount of liberated biotin after
      hydrolysis, it does not suffer from steric hindrance problems associated with the
      ability of biotin on a protein surface to displace HABA from avidin. Therefore,
      this method can provide a more accurate determination of the extent of
      biotinylation. It was also determined that the acid hydrolysis of the
      biotinylated protein was more effective in releasing the conjugated biotin
      compared to enzymatic digestion by proteinase K.

PMID- 9026044
TI  - Partner with your pharmacist to improve prescription compliance.

PMID- 9026045
TI  - The C5 Unit: a semi-automatic cell culture device suitable for experiments under
      microgravity.
AB  - This paper presents data on a novel, semi-automatic cell culturing device called
      'C5 Unit' (connectable circuit cell culture chamber) which was developed and
      adapted to the quality and size criteria set by the characteristics of the ESA
      Biorack. The suitability of the hardware for culturing cells under microgravity
      conditions was demonstrated by successful culture of primary mouse cells from
      neonatal cerebellum and testis aboard the Space Shuttle during the IML-2 mission.

PMID- 9026046
TI  - [Vincenzo Tiberio, a precursor of penicillin studies].

PMID- 9026047
TI  - [The spread of Mycoplasma infections].

PMID- 9026048
TI  - [The measurement of microbial contamination of the air. I].

PMID- 9026049
TI  - [Total environmental exposure to chlorinated solvents: studies of exposure
      markers].

PMID- 9026050
TI  - [Treatment of the instruments in the digestive endoscopy centers of Lazio].

PMID- 9026051
TI  - [Protection from carcinogenic agents in work environments: considerations on
      Title VII of Legislative Decree 626/94].

PMID- 9026052
TI  - The protection of health in the workplace Legislative Decrees 626/94 in Italy.

PMID- 9026053
TI  - Preparation of transcriptionally active nuclear extracts from mammalian tissues.

PMID- 9026054
TI  - [Reconstruction of the loss of bone substance of the forearm by cubitalization of
      the radius (one bone forearm). Apropos of 6 cases].
AB  - Extensive forearm bone loss, whatever its etiology, presents a difficult
      reconstruction problem. This is mainly the case in the presence of lesions of the
      interosseous membrane associated with the radio-ulnar joint. When preservation of
      forearm rotation is not possible, cubitalization of the radius and reconstruction
      of the forearm by creation of a "one bone forearm" seems to be an excellent
      salvage technique both functionally and cosmetically. Our experience concerns six
      clinical cases; two of these cases are original and give the authors the
      opportunity to describe a new reconstructive technique of the distal humerus and
      elbow by vascularized transfer of the radius onto the radial artery (with a
      cutaneo-osseous transfer in one case). The etiology of the bone defect included
      severe trauma in three cases, and a Volkman's syndrome complicated by
      osteomyelitis in one case. Two cases represent an original technique of
      reconstruction of the distal humerus by a vascularised transfer of the radius
      onto the radial artery. Forearm reconstruction is performed by cubitalization of
      the radius. The etiology was traumatic in one case and neoplastic in another, and
      a cutaneo-osseous transfer was performed in the latter case. In this difficult
      problem of bone reconstruction, a favorable functional and cosmetic result was
      obtained in our series.

PMID- 9026055
TI  - [Kienbock's disease treated by shortening osteotomy of the radius. Analysis of
      the results apropos of 13 cases].
AB  - A series of 13 cases of Kienbock's disease, treated by shortening of the radius,
      operated between 1975 and 1995, is presented. This series consisted of 7 males
      and 6 females with a mean age of 27.5 years (range: 17 to 37 years). The dominant
      hand was affected in 12 cases. 6 men and 5 women performed heavy work. The mean
      period between the first symptoms and the operation was 18 months (range: 3
      months to 6 years). In 10 cases, pain was severe and limited activities; in 3
      cases, pain was moderate with partial limitation of activity. 8 cases had a
      mobility greater than 75% compared to the healthy side. 5 cases had a mobility of
      approximately 50%. None of the cases had a mobility less than 25%. Strength was
      not measured preoperatively with the JAMAR dynamometer. The standard radiographic
      assessment included an AP palm-plate film (raised palm) and a true profile on a
      small board. This radiographic assessment established, for each case: the Decoulx
      and Lichtmann classification, the radioulnar index, the angle of the radial slope
      and the lunate fossa, collapse of the carpus according to Youm and McMurtry.
      There were two stage 1, three stage 2, eight stage 3 (six stage 3A, and two stage
      3B) and no stage 4. The radioulnar index was negative in 10 cases, zero in 1
      case, and positive in 2 cases. The mean angle of the radial slope was 23 degrees,
      the mean angle of the lunate fossa was 10.8 degrees, the mean height of the
      carpus was 0.476. The incision was anterior in 7 cases, and posterolateral in 6
      cases. The mean shortening was 5 mm (range: 4 to 6 mm). Patients were reviewed
      with a mean follow-up of 5 years (range: 10 months to 12 years). The analysis
      according to Michon's criteria revealed 3 excellent results, 9 good results, 1
      moderate result and no poor results. All patients were able to resume their
      previous occupation. Five no longer had any pain, 6 had moderate and rare pain, 2
      patients presented pain limiting activity. 10 patients presented a mobility
      greater than 75% compared to the healthy side. In 2 cases, the mobility was
      greater than 50%. In 9 cases, the strength was greater than 75% compared to the
      healthy side, and in 4 cases, it was greater than 50%. Radiological assessment,
      all stages combined, showed 4 improvements, 7 stabilizations, 2 deteriorations.
      There was no correlation between the height of the carpus (which varied only very
      slightly postoperatively) and the clinical or radiological course. In this series
      of 13 patients; shortening osteotomy gave results on all stages of the disease.
      There was no correlation between the clinical and radiological course of the
      lunate, and the following factors: age, preoperative radiographic stage,
      instability of the carpus, position of the plate. On the basis of the results of
      our series, it appears important to increase the angle of the lunate fossa and to
      obtain an angulation greater than 12 degrees 5 and to maintain a negative
      radioulnar index. The 2 cases of radiological deteriorations corresponded to a
      positive postoperative radioulnar index, while the index remained negative in the
      4 cases of improvement; all cases in which the angulation of the lunate fossa was
      greater than 12 degrees stabilized or improved radiologically, regardless of the
      preoperative stage. Despite contradictory theories, we believe, in the light of
      our series, that an angulation of the lunate fossa greater than 12 degrees and
      that a negative radioulnar index appear to be decisive criteria in the course of
      Kienbock's disease treated by shortening of the radius.

PMID- 9026056
TI  - [A case of arthritis of the wrist caused by Mycobacterium marinum. Review of the
      literature].
AB  - The authors report the case of a woman aquarium keeper who developed septic
      arthritis of her right wrist due to Mycobacterium marinum. Clinical status and
      history, histopathologic and microbiologic characteristics are reviewed and
      discussed. The authors emphasize the importance of urgent and aggressive surgery
      combined with antimicrobial chemotherapy.

PMID- 9026057
TI  - [The vascularization of the common synovial sheath and the tendons of the flexor
      muscles of the carpal tunnel].
AB  - The detailed anatomy of the tendon apparatus, the blood supply of the superficial
      (FDS) and profundus (FDP) flexor muscles and the blood supply of the common
      synovial sheath in the carpal tunnel were studied on 200 hundred upper
      extremities from fresh human cadavers. The injection of coloured latex or the
      aqueous solution of India ink and gelatin revealed a complex arterial network.
      Dissection of the carpal tunnel revealed the existence of different sources of
      the blood supply of the tendons of the flexor muscles and carpal sheath. The
      different sources and zones of vascularization are described. This study concerns
      the synovial and tendinous apparatus of the flexor muscles as well as their blood
      supply in the carpal tunnel. These data may be of interest hand surgeons.

PMID- 9026058
TI  - [The pisiform bone: sesamoid or carpal bone?].
AB  - In man, the pisiform bone occupies an unusual place among the carpal bones. It is
      situated in an anterior plane to the other bones, sheathed within the tendon of
      the flexor carpi ulnaris, and ossifying almost four years the last of the carpal
      bones. Many theories have tried to explain the presence of this "exceptional"
      bone: the first theory, proposed by Flower and Mivart, suggested the possibility
      that this bone could be a sesamoid. The second theory supposes a polydactyl hand,
      assuming that polydactyly preceded pentadactyly; the pisiform would then be a
      post-minimus vestigial bone according to Bardeleben. Finally, Gegenbauer and
      Gillies, proposed a primary pentadactyl hand in which the carpus would be
      composed of three proximal elements, generally two central, and five distal. The
      pisiform would either be a derivative of the central series, or a distinct
      element in the carpus. This last theory appears to be the most likely. The
      primary carpus would therefore have consisted of 12 bones arranged in 3 distinct
      rows, a proximal row of 3 bones, a central row of 4 bones, and a distal row of 5
      bones. According to this theory, the most ulnar of the central would have been
      displaced to the medial limit of the carpus, to become the pisiform.

PMID- 9026059
TI  - Developmental biology of Urodeles.

PMID- 9026060
TI  - Intranasal tooth in a patient with cleft lip and alveolus.

PMID- 9026061
TI  - AIDS primary central nervous system lymphoma.
AB  - The incidence of primary central nervous system lymphomas is increased several
      1000-fold in AIDS patients. These are B-cell malignancies consistently associated
      with Epstein-Barr virus. They typically occur late in the course of HIV infection
      and are associated with a very short median survival. The pattern of Epstein-Barr
      virus gene expression is indicative of severe immunocompromise. Radiographic
      differentiation from toxoplasmosis remains a problem. Polymerase chain reaction
      amplification of Epstein-Barr virus DNA in cerebrospinal fluid, 18F-fluoro
      deoxyglucose-positron emission tomography scanning, and 201-thallium single-photo
      emission CT are all promising noninvasive or minimally invasive diagnostic
      procedures that may obviate the need for brain biopsy in the future. Occasional
      patients have long remissions after therapy but most patients die within a few
      months. A possible role for combined modality therapy, including combination
      chemotherapy, is being explored.

PMID- 9026062
TI  - E.P. Pope Memorial Award to Dr. James E. Pearson.

PMID- 9026063
TI  - Experimental infection of swine with a sandfly (Lutzomyia shannoni) isolate of
      vesicular stomatitis virus, New Jersey serotype.

PMID- 9026064
TI  - Identification of parvovirus-like particles associated with three outbreaks of
      mortality in young pheasants (Phasianus colchicus).

PMID- 9026066
TI  - Latency characteristics of an EPO and LLT mutant of pseudorabies virus.

PMID- 9026065
TI  - Comparative pathogenicity of nine US porcine reproductive and respiratory
      syndrome virus (PRRSV) isolates in a five-week-old cesarean-derived, colostrum
      deprived pig model.
AB  - One hundred forty-six 5-week- old cesarean-derived, colostrum-deprived (CDCD)
      pigs were inoculated intranasally with 1 of 9 US porcine reproductive and
      respiratory syndrome virus (PRRSV) isolates. Differences were found in severity
      of clinical respiratory disease, rectal temperatures (P < or = 0.001), gross lung
      lesions (P < or = 0.001), and microscopic lung lesions (P < or = 0.05). Gross
      lung lesions were generally most severe 10 days postinoculation and were
      distributed primarily in the cranial, middle, and accessory lobes and
      ventromedial portion of the caudal lung lobes. Mean gross lung lesion scores
      estimating the percentage of lung affected by pneumonia at 10 days
      postinoculation ranged from 16.7% +/- 2.8% (mean +/- SEM, n = 10) for isolate ISU
      51 to 62.4% +/- 5.7% (n = 10) for isolate ISU-28. Microscopic lung lesions were
      characterized by hyperplastic and hypertrophied type 2 pneumocytes, septal
      infiltration by mononuclear cells, and accumulation of necrotic alveolar exudate.
      Lymph node follicular hyperplasia and focal necrosis was seen with all 9
      isolates. This CDCD pig model was useful for demonstration of significant
      differences in pathogenicity among US PRRSV isolates. This difference in
      pathogenicity may help explain the variation of severity of clinical disease
      observed in field outbreaks of porcine reproductive and respiratory syndrome and
      should provide for meaningful comparison of PRRSV genotypes.

PMID- 9026067
TI  - Pathologic responses of lambs to experimental inoculation with Acholeplasma
      laidlawii.

PMID- 9026068
TI  - Multiple serotypes and strains of Streptococcus suis in naturally infected swine
      herds.

PMID- 9026070
TI  - Outbreak of diarrhea associated with Enterococcus durans in piglets.

PMID- 9026069
TI  - In vitro susceptibilities of selected obligate anaerobic bacteria obtained from
      bovine and equine sources to ceftiofur.

PMID- 9026071
TI  - Pneumocystis carinii pneumonia in dogs--a diagnostic challenge.

PMID- 9026072
TI  - Visceral neosporosis in a 10-year-old horse.

PMID- 9026073
TI  - Tetratrichomonas gallinarum encephalitis in a mockingbird (Mimus polyglottos).

PMID- 9026074
TI  - Urethral polyps in Vietnamese pot-bellied pigs.

PMID- 9026075
TI  - An improved method for monensin in feeds.

PMID- 9026076
TI  - A pseudorabies virus mutant with deletions in the latency and early protein O
      genes: replication, virulence, and immunity in neonatal piglets.
AB  - The pathogenicity of a double mutant of pseudorabies virus (PRV) with deletions
      in the latency gene and the early protein O gene was examined. In comparison to
      the parent Indiana-Funkhauser virus, the ability of this mutant to replicate and
      to cause disease in piglets is greatly reduced. At an infection dose that caused
      no clinical signs in 5-day-old neonatal piglets, this mutant was capable of
      eliciting solid protective immunity against a lethal PRV challenge. Thus, the
      double-gene deletion attenuates PRV but does not affect its immunogenicity. These
      features may be desirable for inclusion into future PRV vaccines.

PMID- 9026077
TI  - Feline leukemia virus detection by ELISA and PCR in peripheral blood from 68 cats
      with high, moderate, or low suspicion of having FeLV-related disease.
AB  - Clinicopathologic criteria were used to group 68 cats according to high,
      moderate, or low suspicion of having feline leukemia virus (FeLV)-related
      disease. Peripheral blood samples were tested for FeLV antigen by enzyme-linked
      immunosorbent assay (ELISA) and for FeLV DNA by polymerase chain reaction (PCR).
      There was no significant difference between ELISA and PCR results in the 68 cats.
      In the high-suspicion group, 46%(11/24) of cytopenic cats were test positive
      (ELISA and PCR) and 87% (13/15) with hemopoietic neoplasms were test-positive.
      Also within the high suspicion group, test-positive cats were 2.5 times more
      likely to die within the 1 year follow-up period than were test-negative (ELISA
      and PCR) cats. Among cats in the moderate-suspicion group, 15% (2/13) were test
      positive, and none (0/16) of the cats in the low suspicion group was test
      positive. The relative risk of a positive test (ELISA and PCR) in the high
      suspicion group was 3.7 times that for the moderate-suspicion group and 22.8
      times that for the low suspicion group. There was no significant difference in
      the relative risk of a positive test result between the moderate and low
      suspicion groups. The results indicate that FeLV detection by PCR can be adapted
      for diagnostic purposes using peripheral blood samples, however, results do not
      differ significantly from FeLV ELISA results. Also, a proportion of cats with a
      high suspicion of having FeLV-related cytopenia and hemopoietic tumors are
      negative for both circulating FeLV antigen and DNA. These cats may not have FeLV
      related disease, or FeLV may exist in a disease-producing but nonreplicating form
      ultimately detectable by PCR in tissues other than peripheral blood.

PMID- 9026078
TI  - Detection of porcine reproductive and respiratory syndrome virus in cell cultures
      and formalin-fixed tissues by in situ hybridization using a digoxigenin-labeled
      probe.
AB  - A nonradioactive in situ hybridization method is described for the detection of
      porcine reproductive and respiratory syndrome virus (PRRSV) in cell cultures and
      in formalin-fixed paraffin-embedded tissue sections originating from
      experimentally infected pigs and from 1 field case. A 174 bp cDNA probe targeting
      the viral RNA encoding the nucleocapsid protein of a Canadian PRRSV isolate was
      generated by polymerase chain reaction. The cDNA probe was labeled by random
      priming with digoxigenin-dUTP using a commercially available kit. The ability of
      the digoxigenin-labeled probe to specifically detect PRRSV RNA was tested on
      cultured cells infected with 6 Canadian PRRSV isolates, a US PRRSV isolate and
      the European Lelystad isolate. The probe detected all Canadian PRRSV isolates
      tested as well as the US PRRSV isolate but did not detect the Lelystad isolate.
      In addition, when tested on formalin-fixed paraffin-embedded tissue sections from
      pigs experimentally infected with several Canadian isolates and from a field
      case, a strong signal without background staining was obtained. Our results
      indicate that nonradioactive in situ hybridization could represent a useful tool
      for the detection of PRRSV in routinely fixed and processed tissues. In situ
      hybridization could also be used to differentiate infection by North American and
      European Lelystad-like PRRSV isolates.

PMID- 9026079
TI  - Clinicopathologic variation in raccoons infected with different street rabies
      virus isolates.
AB  - Ten raccoons were divided into two random groups (groups 1 and 2) of five animals
      each. Group 1 raccoons were inoculated intramuscularly in the masseter muscle
      with a raccoon rabies virus isolate obtained from a natural case of raccoon
      rabies from the northeastern USA. Group 2 raccoons were infected by a similar
      route with a Latin American canine isolate of rabies virus. Raccoons either died
      suddenly or developed neurologic signs compatible with rabies. Clinical signs of
      rabies in group 1 raccoons were more severe than in group 2. Raccoons in group 1
      either died acutely or were euthanized within 25 days (mean +/- SD = 20.6 +/- 2.7
      days) postinfection, whereas all group 2 raccoons showed neurologic signs and
      were euthanized within 17 days (14.2 +/- 2.2 days) postinfection. Light
      microscopic findings revealed extensive nonsuppurative encephalitis predominantly
      located in the cerebrum and brain stem of raccoons in group 1, whereas in group 2
      raccoons the lesions were confined to the brain stem regions. In group 1
      raccoons, Negri bodies were commonly seen on hematoxylin and eosin (HE)-stained
      sections of brain and in ganglion cells of 5 other tissues (trigeminal nerve,
      salivary glands, duodenum, pancreas, adrenal gland). Negri bodies, however, were
      either absent or were only occasionally observed in corresponding tissues of
      raccoons infected with the canine strain (group 2). Paraffin-embedded tissue
      sections were also examined for Negri bodies by an immunoperoxidase test, which
      revealed results similar to the HE findings. Results of this study are compared
      with histopathologic and immunohistochemical findings in raccoons naturally
      infected with rabies.

PMID- 9026080
TI  - Diagnostic serologic testing of cage and aviary birds for chlamydiosis and
      suggested confirmatory testing.
AB  - A 2 x 2 contingency table was constructed to demonstrate the relationships
      between detectable chlamydial antibody activity and clinical health status of
      tested birds. The table revealed that 65.5% of clinically ill birds were antibody
      positive by elementary body agglutination (EBA) (> or = 10 titers) and 59.0% were
      antibody positive by latex agglutination (LA). Thus, EBA was slightly more
      sensitive than LA in detecting antibody activity. Of the clinically normal birds,
      96.7% were antibody negative (< 10 titers) by EBA and 98.3% were antibody
      negative by LA. Individual serum or plasma samples from a group of mixed types of
      psittacine birds and cockatiels were tested as a separate group, and
      relationships between EBA-detectable antibody activity and health status were
      obtained from a 2 x 2 contingency table. Sixty-six percent of birds clinically
      ill with signs of chlamydiosis in the mixed-type group were antibody positive,
      whereas only 32.3% of clinically ill cockatiels were antibody positive.
      Statistical analysis of the contingency table using a chi-square test
      demonstrated that the EBA test differentiates between individual birds on the
      basis of health status (P < 0.001). When testing paired serum or plasma samples
      by EBA, LA, and direct complement fixation (DCF), the highest percentage of
      significant (> or =4-fold change) titer decreases was detected by LA, and the
      highest percentage of significant titer increases was detected by DCF. Examples
      of EBA, LA, and DCF titers in paired and multiple serum or plasma samples are
      presented to show the variety of responses that can occur. Results reflected
      variations seen in individual testing of birds with titer variability seen in the
      first sample tested. Additional types of testing believed necessary for
      confirming or ruling out an infectious process in birds are outlined. The current
      interpretations of serologic results are given.

PMID- 9026081
TI  - Lung and nasal lesions caused by a swine chlamydial isolate in gnotobiotic pigs.
AB  - The objective of this study was to determine whether a chlamydial isolate
      recovered from nasal swabs from swine with pneumonia could cause pneumonia and
      rhinitis in gnotobiotic pigs. The identity of the isolate currently is unknown,
      but it shares characteristics with Chlamydia trachomatis. After propagation in
      Vero cells and preparation of the inoculum (2.5 x 10(10) inclusion-forming
      units/ml), chlamydiae were instilled into nostrils (1.0 ml/nostril) and lungs
      (2.0 ml intralaryngeally) of 15 anesthetized 3-day-old gnotobiotic piglets. Five
      age-matched gnotobiotic piglets were anesthetized and sham infected with
      uninfected cell culture lysates. Two treated piglets were moribund and 2 were
      severely dyspneic prior to necropsy 7 days postinfection (DPI), whereas remaining
      treated piglets showed mild dyspnea upon exertion throughout the study. All
      treated piglets developed diarrhea. All treated piglets necropsied 7-21 DPI had
      extensive consolidation in cranial, middle, and accessory lung lobes; a majority
      of these piglets also had extensive consolidation in the caudal lobes. Treated
      piglets necropsied 28 and 35 DPI had a lobular pattern of consolidation in all
      lung lobes. Histologically, lesions in lungs from treated piglets necropsied 7,
      14, and 21 DPI were characterized by bronchointerstitial pneumonia with foci of
      type II pneumocyte hypertrophy and hyperplasia; pneumocytes and bronchial and
      bronchiolar epithelial cells were markedly vacuolated. Alveolar macrophages,
      peribronchitis, peribronchiolitis, and perivasculitis were seen in lungs from
      treated piglets necropsied 28 and 35 DPI; those necropsied 28 DPI also had foci
      of lymphohistiocytic and plasmacytic infiltrates. Turbinate lesions in all
      treated piglets were characterized by mild multifocal lymphoplasmacytic and
      occasionally neutrophilic rhinitis. Immunohistochemistry detected chlamydial
      antigen in bronchial and bronchiolar epithelial cells, pneumocytes, and
      inflammatory cells in treated piglets necropsied 7, 14, and 21 DPI. Positive
      staining was limited to alveolar macrophages in treated piglets necropsied 28 and
      35 DPI. Chlamydial antigen was detected in turbinate epithelial cells at all
      necropsy intervals. Ultrastructurally, chlamydiae were seen with glycogen
      particles in vacuoles or free in the cytoplasm of bronchial and bronchiolar
      epithelial cells and pneumocytes. The results indicated that the chlamydial
      isolate used in this study is a pathogen in gnotobiotic pigs.

PMID- 9026082
TI  - Use of species-specific oligonucleotide probes to detect Mycoplasma
      gallisepticum, M. synoviae, and M. iowae PCR amplification products.
AB  - Three digoxigenin-labeled oligonucleotide probes, complementary to the variable
      region of the 16S ribosomal RNA (rRNA) gene of Mycoplasma gallisepticum, M.
      synoviae, and M. iowae were designed. The oligonucleotides were used in a dot
      blot hybridization assay. The target DNA is a 780-bp fragment of the 16S rRNA
      gene of avian mycoplasmas amplified by a single set of primers (multispecies
      polymerase chain reaction [PCR]). The oligonucleotide probes were specific for
      their corresponding PCR products at hybridization conditions of 56 C and 50%
      formamide. The detection limit of the dot blot hybridization assay was
      approximately 70, 50, and 30 colony-forming units for M. gallisepticum, M.
      synoviae, and M. iowae, respectively, per 4 microliters of PCR. In general, the
      oligonucleotide probe dot blotting assay was a more sensitive and effective
      method of detecting PCR products than detection by gel electrophoresis.

PMID- 9026083
TI  - Evaluation of antibiotics for the elimination of the tonsillar carrier state of
      Streptococcus suis in pigs.
AB  - Seventy clinically normal 13-day-old crossbred pigs from 10 litters from a
      Streptococcus suis-infected herd were randomly assigned by litter and weight to 7
      groups of 10 pigs each to determine whether different antibiotic regimens would
      eliminate the tonsillar carrier state of S. suis. Six antimicrobial regimens were
      tested: penicillin intramuscularly (IM) once daily (s.i.d.) for 3 consecutive
      days; penicillin IM s.i.d. for 5 consecutive days; ampicillin IM s.i.d. for 5
      consecutive days; ampicillin per os s.i.d. for 5 consecutive days; ampicillin
      intranasally s.i.d. for 5 consecutive days; and ceftiofur sodium IM s.i.d. for 5
      consecutive days. The seventh group consisted of untreated control pigs.
      Tonsillar swab samples were collected before treatment, and tonsillar tissue
      samples were collected after treatment for cultural examination for S. suis.
      Streptococcus suis was identified in pigs from all groups prior to treatment and
      after treatment. Pigs did not have clinical signs of disease during the study.
      All antimicrobial treatments tested in this study failed to eliminate the
      tonsillar carrier state of S. suis. Early weaning and medication used in this
      study were not effective for the elimination of the tonsillar carrier state of S.
      suis in pigs. Optimization of management and environment of pigs coupled with
      strategic medication of clinically ill animals should be used for control and
      prevention of mortality caused by streptococcosis.

PMID- 9026084
TI  - Development of murine monoclonal antibodies for the immunohistochemical diagnosis
      of systemic bovine aspergillosis.
AB  - Murine monoclonal antibodies (MAbs) against water-soluble somatic antigens (WSSA)
      and the wall fraction (WF) from Aspergillus fumigatus were produced by fusion of
      splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. The
      supernatants of in vitro cultured hybridomas were initially screened for
      reactivity with the WSSA and the WF from A. fumigatus and WSSA of other fungi in
      an enzyme-linked immunosorbent assay (ELISA). Supernatants reacting only with A.
      fumigatus antigens were subsequently screened for homologous and heterologous
      reactivity with immunohistochemical techniques using formalin-fixed, paraffin
      embedded tissues from experimentally infected mice. Because of a high
      immunohistochemical reactivity with homologous fungi, 4 MAbs raised against A.
      fumigatus WSSA and WF were selected for a further evaluation of cross-reactivity
      (diagnostic specificity) in immunohistochemical and immunoblotting assays. In
      immunohistochemical assays, all MAbs raised against WSSA cross-reacted heavily
      with a number of other fungal species. All 4 MAbs (MAb-WF-AF-1-4) raised against
      the WF reacted strongly with hyphae of Aspergillus spp.; hyphae of Scedosporium
      apiospermum were also strongly labeled by MAb-WF-AF-3 and -4. The 2 specifically
      reacting MAbs (MAb-WF-AF-1 and -2) were of the IgM biotype and were
      precipitating, and in immunoblotting experiments both bound to a 106-kD antigen
      of the WF, whereas they did not bind to WSSA of A. fumigatus. One of the 2
      aspergillosis-specific MAbs (MAb-WF-AF-1) was used to screen 145 mycotic lesions
      of cattle. The diagnoses on bovine lesions obtained by MAb-WF-AF-1 were compared
      with results based on reactivity with heterologously absorbed polyclonal
      antibodies and, for some lesions, to culture results. In the vast majority of
      lesions (n = 133), the MAb-WF-AF-1 and the polyclonal anti-Aspergillus antibodies
      reacted in a similar pattern, i.e., positively in 41 aspergillosis lesions and
      negatively in 92 zygomycotic lesions. Hyphae in 3 of 12 lesions that were not
      stained by the polyclonal antibodies reacted with the specific MAb-WF-AF-1; i.e.,
      aspergillosis was diagnosed. The characteristics of the 2 MAbs (MAb-WF-AF-1 and 
      2) raised against the WF of A. fumigatus in ELISA and immunoblotting and
      immunohistochemical assays justify their application for the in situ diagnosis of
      systemic aspergillosis of cattle.

PMID- 9026085
TI  - Histologic evaluation of the crop for diagnosis of proventricular dilatation
      syndrome in psittacine birds.
AB  - Histologic sections of crop tissue were evaluated for the presence of
      lymphoplasmacytic infiltrates within mesenteric ganglia. All birds with
      proventricular dilatation syndrome that had lymphoplasmacytic infiltrates in crop
      ganglia had similar infiltrates in the proventricular and/or ventricular ganglia.
      False-negative crop biopsy results occurred approximately 24% of the time. More
      invasive procedures, such as proventricular or ventricular biopsy, may be
      necessary if the crop biopsy is nondiagnostic in a bird with clinical signs of
      proventricular dilatation syndrome.

PMID- 9026086
TI  - Pyrrole detection and the pathologic progression of Cynoglossum officinale
      (houndstongue) poisoning in horses.
AB  - Houndstongue (Cynoglossum officinale), a noxious weed that contains pyrrolizidine
      alkaloids (PAs), infests pastures and fields in the western United States and
      Europe. The purpose of this study was to develop techniques to better diagnose PA
      poisoning and describe the progression of gross and microscopic lesions caused by
      houndstongue intoxication. Six horses were gavaged daily with a suspension of
      houndstongue containing 5 or 15 mg/kg total PA for 14 days. Two horses were
      treated similarly with ground alfalfa as controls. Liver biopsy samples and serum
      biochemical and hematologic values were evaluated biweekly. Within 7 days after
      dosing, horses treated with 15 mg/kg PA developed severe liver disease
      characterized by altered bile acid metabolism, elevated serum enzymes, and
      extensive hepatocellular necrosis with minimal periportal fibrosis and biliary
      hyperplasia. The condition of these animals continued to deteriorate, and they
      were euthanized. For several weeks after dosing, horses treated with 5 mg/kg PA
      were depressed, had transient elevations of serum enzymes and bile acids, and
      developed minimal periportal hepatocellular necrosis with fibrosis. The
      biochemical changes resolved by 6-8 weeks; however, the histologic disease
      persisted with extensive megalocytosis by week 14. Throughout the study, the rate
      of hepatocellular proliferation remained constant. Biliary cells had an increase
      in mitotic rate that correlated with the histologic changes. Hepatic tissue-bound
      pyrroles (PA metabolites) were identified in necropsy samples of treated animals
      using gas chromatography/mass spectrometry and photometrically with Ehrlich's
      reagent. These findings suggest that pyrrole extraction and identification are
      useful in documenting PA exposure and that houndstongue is extremely toxic to
      horses.

PMID- 9026087
TI  - Chromosomal aneuploidy associated with spontaneous abortions and neonatal losses
      in cattle.
AB  - Pericardial sac samples from 77 bovine aborted fetuses and stillborn calves were
      submitted for tissue culture; cells from 55 of these samples were grown
      successfully in culture. Six of the 55 karyotyped fetuses (10.7%) had an abnormal
      chromosome complement, in 3 of which (5.5%) the abnormality was probably the
      cause of death. This level of abnormality is relatively high when one considers
      that most fetuses were >8 months gestational age. Approximately 5-7% of human
      stillbirths and 50% of first-trimester aborted fetuses have chromosome anomalies.
      If a similar situation exists in cattle, as suggested by these data, chromosome
      abnormalities may be a major cause of early fetal loss in cattle. Most
      chromosomally abnormal fetuses had multiple malformations, which suggests that
      the diagnostic use of chromosome analysis is most cost effective for malformed
      fetuses and newborns. Twins were present in a higher proportion of these fetuses
      than expected based on their incidence among liveborn cattle.

PMID- 9026088
TI  - Factors affecting isolation and propagation of bovine coronavirus in human rectal
      tumor-18 cell line.

PMID- 9026089
TI  - Evaluation of two antigen-capture ELISAs using polyclonal or monoclonal
      antibodies for the detection of bovine coronavirus.

PMID- 9026090
TI  - Ultrastructure, distribution, and density of lamellar bodies in human peritoneum.
AB  - OBJECTIVE: To determine the ultrastructure, relative density, and location of
      lamellar bodies in the various regions, structures, cells, and intercellular
      matrix in normal human peritoneum; to carry out engineering analysis of the role
      of lamellar structures in serosal lubricancy and deduce what effect this system
      may have on the process of peritoneal dialysis. DESIGN: Five samples of normal
      human parietal peritoneum obtained at elective operation were fixed in a tannic
      acid-glutaraldehyde mixture and submitted to examination by transmission electron
      microscopy. Detailed analysis using reconstruction of serial electron micrographs
      and tracings of montages were employed in determining location, and disposition,
      density, and geometric patterns of lamellar bodies in all levels of the
      peritoneal membrane. RESULTS: Lamellar profiles were found in greatest density
      enmeshed in surface microvilli and in mesothelial cytoplasm. Lamellar bodies were
      frequently observed capping the external portion of mesothelial junctional
      complexes, and within intercellular junctions. Lamellar bodies were also
      encountered in macrophages, both in the peritoneal cavity and submesothelial
      tissue, and also in fibroblasts. Lamellar bodies were present in low density in
      the matrix ground substance of submesothelial connective tissue, in blood vessel
      walls between smooth muscle, in endothelial cell cytoplasm, and in vascular
      lumina. CONCLUSIONS: Three-dimensional analysis of lamellae on mesothelial
      surfaces indicates that an arrangement of constantly changing microscopic spheres
      and cylinders would act at "ball and roller bearings" among the microvilli for
      the lubrication of opposing surfaces. The entrapment of fluid in lamellar
      bubbles, which in normal peritoneum fill the microvillous layer, would, if
      maintained in peritoneal dialysis, constitute a stagnant layer of considerable
      stability and inertia.

PMID- 9026091
TI  - Qualitology and qualitometrics.

PMID- 9026093
TI  - [Establishment of an emergency CT service by means of teleradiology].
AB  - The teleradiological connection between the University Hospital in Innsbruck,
      Tyrol, and the Regional Hospital in Zwettl, Lower Austria, is presented as an
      example of a routine online connection of two helical CT systems. PURPOSE: To
      establish a practicable and cost-efficient emergency CT service in a remote
      hospital during night time and on weekends. MATERIAL AND METHODS: Online
      connection of a GE HiSpeed Advantage-Spiral-CT and a GE Prospeed-Spiral-CT via
      two Sun SPARC 10 work stations and ISDN. RESULTS: The transmission of 121 CT data
      sets from 116 patients revealed a sufficiently fast average transmission time of
      15 (6-53) minutes and average transmission costs of DM 9.00 per examination. The
      system was technically reliable, cost-efficient and practicable in clinical
      routine application. CONCLUSIONS: Teleradiology enables remote hospitals to
      provide an emergency CT service even if there is no radiological specialist
      available outside office hours. Thus time-consuming and cost-intensive patient
      transfers and delay of therapy can be reduced.

PMID- 9026092
TI  - [Diagnostic radiology development, medical ranking, socioeconomic significance.
      At the threshold of the second century of radiology].

PMID- 9026094
TI  - [Spontaneous fatty tissue necrosis of the omentum majus and epiploic appendices:
      clinical, ultrasonic and CT findings].
AB  - To describe US and CT findings of primary epiploic appendicitis and segmental
      infarction of the omentum. MATERIAL AND METHODS: From 1986 through 1996 thirteen
      patients presented with these pathological findings at our institution (6
      patients with greater omental infarction and 7 patients with epiploic
      appendicitis). US (n = 13) and CT findings (n = 7) were retrospectively reviewed.
      RESULTS: US revealed moderately hyperechoic, ovoid lesions adherent to the
      peritoneum. On CT scans the masses appeared as areas of fat with slightly
      increased attenuation and sometimes with hyperattenuating peripheral rims.
      Secondary omental or appendiceal involvement caused by inflammation of adjacent
      organs has to be excluded. CONCLUSION: Segmental infarction of the omentum and
      primary epiploic appendicitis have characteristic US and CT features that enable
      the correct diagnosis.

PMID- 9026095
TI  - [MR-Cholangiopancreatography as a single-shot projection: techniques and results
      of 200 examinations].
AB  - PURPOSE: Evaluation of utility and value of a selective projection technique for
      bile and pancreatic ducts in MRI. MATERIAL AND METHODS: 200 patient examinations
      of the pancreaticobiliary duct system using a turbo-SE pulse sequence in "single
      shot" technique were evaluated in retrospect concerning anatomic display and
      diagnostic accuracy compared to surgery, ERCP, i.v. cholangiography, ultrasound
      and clinical course. RESULTS: Non-dilated ducts allowed visualisation of
      gallbladders in 78%, common bile ducts in 97%, cystic ducts in 80%, intrahepatic
      main ducts in 71% and pancreatic main ducts in 69%. When dilatation was present,
      all common bile, intrahepatic main and pancreatic ducts were visible. Display of
      cystic ducts and gallbladders with a detection rate of 69 and 85%, respectively,
      did not improve. Sensitivities for diagnosing papillary stenoses (n = 6),
      pancreatic ductal stenoses and dilatation (n = 13), compressions and dilatations
      of the biliary tree (n = 33) as well as for one choledochal cyst were 100%.
      Choledocholithiasis could correctly be predicted in 11/15 cases (73%),
      cholecystolithiasis in 71/120 cases (59%). CONCLUSION: "Single-shot" MR
      cholangiopancreatography is a fast and non-invasive modality which can replace
      i.v. cholangiography and restrict the indication for ERCP to therapeutic
      indications and problem cases.

PMID- 9026096
TI  - [MR angiography of the carotid arteries using 3D TOF technique with sagittal
      double-volume acquisition using a new head-neck coil].
AB  - PURPOSE: The aim of the study was to assess the value of MR angiography (MRA) in
      sagittal technique compared to DSA in the evaluation of carotid artery stenosis.
      METHODS: 80 carotid arteries in 40 symptomatic patients were prospectively
      studied with DSA and MRA. MRA was carried out by means of 3 D time-of-flight
      technique with a FISP sequence (TE6 ms/TR80 ms, flip angle 25 degrees, FOV 240 x
      210 mm, matrix 157 x 256 mm, in-plane resolution 1.34 x 0.94 mm, partition
      thickness 1.32 mm, slab thickness 45 mm, acquisition time 7 min) using a new head
      neck coll. Data acquisition was performed in sagittal orientation with the
      "double-slab" technique. Imaging quality of the extracranial carotid arteries and
      correctness of quantification of stenosis was performed. RESULTS: Imaging quality
      was good at the origin of the carotid arteries in 65%, at the bifurcation region
      in 98% and near the skull base in 81%. The agreement of DSA and MRA was 96% of
      the normal arteries (24/25), 90% of the severe stenoses (28/31) and 100% of the
      occluded arteries (9/9). CONCLUSION: MRA in sagittal "double-slab" technique is a
      noninvasive technique allowing to detect normal arteries and candidates for
      surgery with a high degree of certainty.

PMID- 9026097
TI  - [Can the high-resolution 13-MHz ultrasonography facilitate the preoperative
      localization and marking of microcalcification clusters?].
AB  - PURPOSE: The value of 13 MHz ultrasound regarding the preoperative localisation
      in combination with mammography were investigated into. MATERIAL AND METHOD: Out
      of 112 mammaographically detected calcifications, 30 (30 patients) were clusters
      of microcalcifications. Out of these, 23 were classified as suspicious of
      malignancy and were preoperatively localised with a 7.5 and 13 MHz probe. Upon
      marking the skin, a fine needle was inserted, and after due correction blue dye
      or coal solution was instilled. RESULTS: Following mammographically shown
      position, 23 clusters of microcalcifications could be localised using the 13 MHz
      probe. A localisation with the 7.5 MHz probe was impossible in all cases. A
      single correction of the needle's site was necessary with 35% (8/23) of patients.
      The maximum distance of the needle's tip in case of misposition measured 11 mm.
      CONCLUSION: Giving a known mammographic position and a sonographic perceptibility
      of clusters of microcalcifications in a maximal depth of penetration of 2 cm, 13
      MHz high resolution ultrasound examination in combination with mammography prove
      to be a valuable means in facilitating the preoperative localisation.

PMID- 9026098
TI  - [Modified manual rt-PA pulse-spray lysis in occlusions of leg arteries and femoro
      popliteal bypasses].
AB  - PURPOSE: The evaluation of local rt-PA pulse-spray-lysis (PSL) by the Katzen
      infusion wire for treatment of thrombosed leg arteries and bypass grafts.
      MATERIAL AND METHOD: 21 patients (mean age 64.4 years) with either occluded leg
      arteries (n = 19) or femorocrural bypass grafts (n = 2) were treated with PSL.
      Mean length of occlusion was 13.2 +/- 11.6 cm. Time of occlusion ranged from less
      than one week to 6 months. RESULTS: In 71.43% (15/21) the occlusions could be
      successfully recanalized with PSL. The mean rt-PA dose was 10.7 +/- 4.9 mg.
      Remaining stenoses were handled with PTA (n = 9) and additional stent
      implantation (n = 3). Additional long-time-lysis with 17.5 mg rt-PA was necessary
      in two cases, the success rate increased to 81% (17/21). The anlde-brachial-index
      increased from 0.38 +/- 0.29 to 0.83 +/- 0.32 within 24 hours after intervention.
      In 4 cases bleeding complications occurred. 5 patients showed reocclusions during
      6 months follow-up. CONCLUSIONS: Local fibrinolysis with rt-PA in PSL technique
      using the Katzen infusion wire is a feasible and promising treatment of
      thrombosed leg arteries and grafts. Even careful and dosage-minimized rt-PA
      application cannot prevent bleeding complications.

PMID- 9026100
TI  - [Experimental results of excimer-laser-PTA in an experimental ex vivo vascular
      model].
AB  - PURPOSE: To evaluate parameters and characteristics of excimer-laser-angioplasty
      on ex-vivo vessel models. MATERIAL AND METHODS: 450 tissue ablations were
      performed on pig aortas, human arteries and fibrin-fixed plaque material. A
      pulsed 308nm-XeCl-laser delivering 120 ns pulses was tested. Ablations were
      analysed depending on frequency (10-40 Hz), energy density (30-70 ml/mm2),
      catheter-material-angle (0-90 degrees) and object-catheter-distance (0-40 mm).
      RESULTS: Vessel recanalisation speeds of up to 0.5 mm/s were achieved on fibrosed
      to slightly calcified human vessel models. In perforation tests on normal to
      slightly fibrosed human vessel walls and vessels of pigs ablation speeds of 0.01
      0.5 mm/s were measured. Perforations on calcified vessels were successful in 50%
      of cases after two minutes application time. Vessel perforations were not
      detected without the support of mechanical power. At catheter-material angles <
      or = 30 degrees a minor damage of the intima could be found. There was no
      evidence of necrosis or coagulation in our studies. CONCLUSION: In-vitro tests of
      human plaque material yield reproducible vessel recanalisation distances of up to
      25 mm at a variable speed from 0.1-0.2 mm/s.

PMID- 9026099
TI  - [Contrast medium supported imaging of tumorous vessels by color Doppler and power
      Doppler mode in animal experiments].
AB  - PURPOSE: The purpose was to determine tumor neovascularisation via colour-coded
      Doppler (duplex) sonography and the "power mode", both visually and
      quantitatively, by means of videodensitometry. MATERIAL AND METHODS: 6 VX2
      tumours of 4 to 11 mm size were implanted in 4 rabbits at various sites. The
      colour-coded duplex sonography and the new sonographic power technique were
      tested before and after having injected a new contrast medium (SH U 616A).
      RESULTS: If no contrast medium was injected, tumour neovascularisation was
      identified in only 50% of the cases. Injection of contrast medium increased
      signal intensity three to fourfold with all examined tumors. Combined use of the
      sonographic method by the power technique with injection of contrast medium is
      outstandingly suitable for tumor vessel imaging even of small tumors, as these
      initial results seem to show. CONCLUSION: If these results are corroborated by
      further studies, contrast-medium supported sonographic technique may possibly
      become established as an alternative method to other imaging procedures.

PMID- 9026101
TI  - [Phantom study of optimization of spiral-CT and 3D reconstruction of the
      tracheobronchial system].
AB  - PURPOSE: To optimise three-dimensional spiral CT of the tracheobronchial tree
      using adequate acquisition and reconstruction parameters for spiral CT of the
      chest. MATERIAL AND METHODS: Qualitative and quantitative assessment of different
      3 D reconstructions of two test objects of the tracheobronchial tree depending on
      section thickness, reconstruction interval, pitch, and reconstruction algorithm
      used in spiral CT (Siemens, Somatom plus S) of the chest. The frequency of volume
      and stairstep artifacts was evaluated. The 3 D reconstructions were generated
      using a seeded VOI-technique (Allegro, ISG). RESULTS: Reduction of artifacts was
      achieved by decreasing section thickness. Increasing overlap of source images,
      lowering the pitch factor, and application of the reconstruction algorithm
      "slim". Section thickness was the single most important factor which was mainly
      responsible for the occurrence of volume artifacts. Stairstep artifacts were
      primarily influenced by the reconstruction interval. CONCLUSION: Spiral CT with a
      section thickness > 4 mm is not adequate for 3 D reconstructions of the
      tracheobronchial tree. Overlapping source images with a pitch of 1 and the
      reconstruction algorithm "slim" can be recommended to reduce artifacts.

PMID- 9026102
TI  - [Presentation of a new self-expanding vascular spiral stent].
AB  - The technical details as well as first clinical results of a newly developed
      Nitinol stent are presented. The spiral-shaped Nitinol stent was implanted in two
      patients with complicated peripheral arterial obstruction after bypass surgery.
      Stent implantation was very exact and technically simple using a special
      implantation catheter. While one patient is free of symptoms three months after
      stent implantation, an early obstruction was observed in the other patient one
      day after the interventional procedure. The specific spiral design allows a
      simple percutaneous extraction of the stent. A cross-over use of the stent seems
      principally possible, but limited due to the length of the implantation catheter
      of 70 cm. Prospective clinical studies are, however, warranted.

PMID- 9026103
TI  - [Virtual cystoscopy based on spiral CT data].
AB  - Simulation of three-dimensional cystoscopy based on helical CT scan data in real
      time in patients with tumours of the urinary bladder. In three patients with
      histologically confirmed carcinoma of the urinary bladder, a helical CT scan with
      double detector technology was carried out preoperatively. A native scan was
      first performed, followed by an examination in the early contrast medium enhanced
      phase. After adequate contrasting of the urinary bladder (30 minutes latency),
      further images were acquired. These data were transferred to a separate graphic
      computer workstation and reconstructed. The results were then compared with the
      cystoscopic and pathohistological findings. All tumours of the urinary bladder
      identified at fiberoptic cystoscopy were also visualised by virtual cystoscopy.
      The best reconstruction results were obtained from data acquired after the 30
      minute latency period. Virtual cystoscopy represents an interesting option in
      helical CT scanning, which is able to visualise polypoid tumours of the urinary
      bladder. Its clinical relevance, however, must be demonstrated in studies with a
      larger number of patients examined.

PMID- 9026105
TI  - [Pulmonary changes in high-resolution spiral CT in Williams-Campbell syndrome].

PMID- 9026104
TI  - [Ileocecal invagination in a patient with HIV infection and non-Hodgkin's
      lymphoma].

PMID- 9026106
TI  - [Disseminated liver abscesses in yersiniosis: diagnosis by ultrasound and spiral
      CT].

PMID- 9026107
TI  - [Spiral CT and color-coded three-dimensional surface reconstruction in the
      diagnosis of mandibulofacial arteriovenous malformation].

PMID- 9026108
TI  - [MR in malignant lymphomas of the female pelvis].

PMID- 9026109
TI  - [Pigmented villonodular synovitis of the lower limb. MR-tomography and histology
      in 3 cases].

PMID- 9026111
TI  - [Dynamic features of the modified state of consciousness during transcendental
      meditation].

PMID- 9026112
TI  - [Reactivity of the basilar artery in the brain of Krushinski-Molodkina line rats
      one day after an audiogenic epileptiform seizure].

PMID- 9026110
TI  - [Proteoglycans and cells].

PMID- 9026113
TI  - [Effect of certain phyto-substances on production of lymphocyte-activating factor
      during rotation stress in mice].

PMID- 9026114
TI  - [Comparative study of lipid peroxidation indicators in the heart, liver and brain
      of rats with varying resistance to hypoxia].

PMID- 9026115
TI  - [Microcirculatory system of paired hamster cheek pouches during occlusion of the
      common carotid arteries].

PMID- 9026116
TI  - [Role of peritoneal macrophages during exposure to natural metabolites in toxic
      hepatitis].

PMID- 9026117
TI  - [Effect of the nootropic agents piracetam and GBS-111 on potential-dependent ion
      channels in the neuronal membrane].

PMID- 9026118
TI  - [Significance of various types of adrenergic receptors for tolerance of the brain
      to complete ischemia].

PMID- 9026119
TI  - [Effect of various suture and auxiliary materials on oxygen-dependent peritoneal
      macrophage function].

PMID- 9026120
TI  - [Effect of ozone on intensity of lipid peroxidation in heart tissue, isolated
      from clinically dead rats].

PMID- 9026121
TI  - [Pharmacologic analysis of phenazepam and flunitrazepam activity when
      administered in extremely low doses].

PMID- 9026122
TI  - [Antiviral activity of several vasodilator agents].

PMID- 9026124
TI  - [Role of the ability of bacteria to inactivate natural anti-infective resistance
      factors in their resistance to blood bactericidal action (blood serum)].

PMID- 9026123
TI  - [Effect of mexidol on the level of monoamine mediators and amino acids in rat
      brain structures].

PMID- 9026125
TI  - [Dynamics of changes in macrophage activity, metabolic activity of the liver, and
      level of cortisol in murine serum when administering bacterial immunostimulants].

PMID- 9026126
TI  - [Effect of interaction of fibroblasts and keratinocytes on interleukin-8
      secretion].

PMID- 9026127
TI  - [Effect of enduracin on the activity of a cholesterol ester transfer protein in
      blood plasma of people with hypercholesteremia].

PMID- 9026128
TI  - [Dynamics of cytotoxicity of blood mononuclear cells in patients with bladder
      cancer during endolymphatic immunotherapy with lymphokine- activated killer cells
      and recombinant interleukin-2].

PMID- 9026129
TI  - [Cytotoxic activity of platelets and peripheral blood mononuclear cells from
      oncology patients and healthy donors].

PMID- 9026130
TI  - [Character of autonomic reactions in patients after total ovariectomy and their
      changes with human fetal tissue transplantation].

PMID- 9026131
TI  - [Effect of a micellar preparation of polyunsaturated phosphatidylcholine on
      platelet aggregation in vitro].

PMID- 9026132
TI  - [DNA-hydrolyzing antibodies in lymphoproliferative disorders].

PMID- 9026134
TI  - [Paneth cells in the gray squirrel (Sciurus carolinensis) and red-cheeked suslik
      (Citellus erythrogenys Brandt)].

PMID- 9026133
TI  - [Evaluation of the adequacy of oxygen consumption by tissues using the "anionic
      burst" parameter].

PMID- 9026135
TI  - [Changes in the peritoneum upon exposure to high-energy laser irradiation].

PMID- 9026136
TI  - [Changes in synapse architectonics of various levels of the visual analyzer after
      exposure to microwaves].

PMID- 9026137
TI  - [Karyometric analysis of the hepatocyte population of field mice from regions
      with different levels of technogenic pollution].

PMID- 9026138
TI  - [Morphological study of somatic muscles in alimentary-toxic paroxysmal
      myoglobinuria].

PMID- 9026139
TI  - [Threshold of cerebral seizure activity and indicators of higher nervous system
      activity in the post-resuscitation period after intracerebral allotransplantation
      of embryonal neocortical tissue].

PMID- 9026140
TI  - [New hot start technology in the polymerase chain reaction].

PMID- 9026141
TI  - Isolation and structure of ciguatoxin-4A, a new ciguatoxin precursor, from
      cultures of dinoflagellate Gambierdiscus toxicus and parrotfish Scarus gibbus.
AB  - A new ciguatoxin congener, ciguatoxin-4A (CTX4A), was isolated from cultures of
      marine dinoflagellate Gambierdiscus toxicus, and its structure was elucidated to
      be 52-epiciguatoxin-4B on the basis of spectroscopic data. Chromatographic and
      spectral comparisons indicated that CTX4A was identical with a structurally
      unelucidated congener known as scaritoxin or SG1.

PMID- 9026142
TI  - Aluminum content of various canned and bottled beverages.

PMID- 9026143
TI  - Concentrations of selected elements in oysters (Crassostrea angulata) from the
      Spanish coast.

PMID- 9026144
TI  - Influence of two naturally occurring abietane monocarboxylic acids (resin acids)
      and a chlorinated derivative on release of the inhibitory neurotransmitter gamma
      aminobutyric acid from trout brain synaptosomes.

PMID- 9026145
TI  - Distribution and elimination of [14C] in saithe (Pollachius virens L.) after
      application of a single dose of [14C] polyhexamethylene hydrochloridebiguanide.

PMID- 9026146
TI  - Toxicological assessment in Tetrahymena of intermediates in aerobic microbial
      transformation of toluene and p-xylene.

PMID- 9026147
TI  - Bioconcentration and toxicity effect on lipid content of aquatic organisms.

PMID- 9026148
TI  - Differences in sensitivity to developmental toxicants as seen in Xenopus and
      Pimephales embryos.

PMID- 9026149
TI  - Uptake and elimination of 14C-phenanthrene by the blue mussel Mytilus edulis L.
      at different algal concentrations.

PMID- 9026150
TI  - Fenbutatin acute toxicity on Artemia nauplii: effects of sublethal concentrations
      on ATPase activity.

PMID- 9026151
TI  - Lead levels in deciduous teeth of children from urban and suburban regions in
      Ankara (Turkey).

PMID- 9026152
TI  - Age-related change in rat testicular ATPase activities in response to HCH
      treatment.

PMID- 9026153
TI  - Insecticide residues in the ambient air of commercial pest control buildings,
      1993.

PMID- 9026154
TI  - Imidacloprid insecticide soil metabolism in sugar beet field crops.

PMID- 9026155
TI  - Mineralization, volatilization, and degradation of carbofuran in soil samples
      from Kenya.

PMID- 9026156
TI  - Agricultural worker exposure to and absorption of permethrin applied to cabbage.

PMID- 9026157
TI  - Determination of HCH and DDT in finger-prick whole blood dried on filter paper
      and its field application for monitoring concentrations in blood.

PMID- 9026158
TI  - DDT and HCH load in mothers and their infants in Delhi, India.

PMID- 9026159
TI  - Accumulation of some heavy metals in various environments and organisms at Goksu
      Delta, Turkiye, 1991-1993.

PMID- 9026160
TI  - Assessment of surface water quality in Cote d'Ivoire.

PMID- 9026161
TI  - HPLC determination of anticoagulant rodenticide residues in animal livers.

PMID- 9026162
TI  - Palatability of leaf material contaminated with Bacillus thuringiensis var.
      kurstaki, to Hydatophylax argus, a detritivorous aquatic insect.

PMID- 9026163
TI  - Toxicity evaluation of 4-chloro-2-methylphenoxyacetic acid by Microtox and
      comparison with FETAX.

PMID- 9026164
TI  - Purgeable aromatic hydrocarbons in water and sediment from the river Morava
      catchment (Slovakia).

PMID- 9026165
TI  - Allometric variations in heavy metal bioconcentration in the asteroid Asterias
      rubens (Echinodermata).

PMID- 9026167
TI  - Neural control.

PMID- 9026166
TI  - Day case cataract surgery in the UK and USA: a comparative study.
AB  - This study is a comparison of healthcare provision for day case cataract surgery
      in the UK and the USA. It commences with a brief history and the political
      influences on the development of healthcare in the USA and the UK, identifying
      recent changes. The high cost of the health system in the USA and the small
      amount of resources consumed by the NHS in the UK are examined. The service
      offered to patients requiring cataract surgery in the UK and the USA are compared
      and the increasing demand for this operation and the challenge of differing
      styles of nursing that day surgery requires are discussed. The study concludes by
      pointing out the consistent expansion of day surgery in both countries in recent
      years, and predicts that, in view of the patient satisfaction and economic
      benefit, the growth of day surgery in the future appears almost unlimited.

PMID- 9026168
TI  - [Sexuality in menopause].

PMID- 9026169
TI  - [Intrauterine fetal stem cell transplantation].
AB  - In utero fetal stem cell transplantation represents a new and still experimental
      therapeutic strategy for diseases related to the hematopoietic system. The broad
      therapeutic implications as well as potentials and limitations of this new
      technique are presented. To date, 6 cases of fetus-to-fetus transplantation have
      been published in the literature.

PMID- 9026170
TI  - [An attempt to qualify and quantify scientific congresses].

PMID- 9026171
TI  - [Gynecological management of patients over 80 years old. Results of a prospective
      study].
AB  - OBJECTIVE: Diagnosis and therapy of gynecologic inpatients who were over 80 years
      of age were analyzed with respect to the desired and the actual management.
      METHODS: A general assessment protocol for diagnostic and therapeutic steps which
      were not carried out in individual cases was drawn up and used for the 96
      patients analyzed. The desired therapy corresponded to the ideal management of a
      60-year-old patient. RESULTS: In two thirds of the cases, the desired therapy
      could be given. For 32 patients, there was a reduction of 5-50%; for only 2
      patients one of > 50%. The most frequent deviation from the ideal therapy was for
      the oncologic patients. CONCLUSIONS: Our conclusions agree with those reported in
      the literature, namely that age alone can not be taken as an argument against
      standard treatment of a patient with a gynecologic disorder. For patients over 80
      years of age, the individual risks and benefits of a particular therapy,
      especially when surgery is involved, should be carefully considered.

PMID- 9026172
TI  - [Delivery from breech presentation with the delivery chair. Initial experiences
      with a new obstetric method].
AB  - OBJECTIVE: To prove safety and practicability of birth from breech presentation
      on a delivery chair. METHOD: In a retrospective study (1990-1995) all fetuses
      with breech presentation and those born using a delivery chair were collected.
      RESULTS: Out of a total of 2,925 fetuses 138 (4.7%) had breech presentation; 82
      of them were born on a delivery chair. CONCLUSIONS: Since 1992 all fetuses with
      breech presentation were born on the delivery chair. The frequency of cesarean
      sections was roughly the same in both collectives (25.5%). We could not identify
      any disadvantages with this new technique.

PMID- 9026173
TI  - [A new surgical aid--the "endo-stitch disposable suture device"--for pelviscopic
      pre-peritoneal Burch incontinence operation. A pilot study].
AB  - OBJECTIVE: It is the therapeutical aim of urogynecology to correct urinary
      incontinence. Which advantages offers the use of the Endo-Stitch needle in
      Burch's pelviscopic colposuspension? METHODS: When extending the field of
      pelviscopic surgery, in a prospective study we performed Burch's pelviscopic
      preperitoneal colposuspension using the disposable Endo-Stitch suture instrument
      in 12 patients with stress incontinence grades 2 or 3. Clinical and urodynamic
      evaluations were performed before and 8.5 months after the pelviscopic operation.
      RESULTS: Clinical and urodynamic follow-up examinations revealed continence in 10
      (83%) out of 12 patients. CONCLUSIONS: Our preliminary experience suggests that
      the pelviscopic incontinence operation by means of the Endo-Stitch needle is a
      good alternative to abdominal colposuspension. Follow-up results of a large
      number of patients will have to prove advantages in contrast to conservative
      surgery.

PMID- 9026174
TI  - [Retroperitoneal technique of laparoscopic adnexectomy after previous
      hysterectomy for prevention of intraoperative organ ruptures].
AB  - OBJECTIVE: The possibility of the reduction of organ ruptures during laparoscopic
      adnexectomy for cystic adnexal masses after previous hysterectomy with
      retroperitoneal techniques was studied. PATIENTS AND METHODS: Twenty-five
      patients with cystic adnexal masses after previous hysterectomy enetered the
      study. The danger of intraoperative organ ruptures was diminished by using the
      retroperitoneal operative technique and a 'salvage bag' (Endopouch). RESULTS: The
      laparoscopic operation was successfuly performed in 23 of 25 patients. In 2
      patients a laparotomy was performed. The frequency of intraoperative ruptures
      decreased with increasing experience (1992 in 7 of 8; 1995 in 1 of 6 patients).
      CONCLUSION: The frequency of intraoperative organ ruptures during laparoscopic
      adnexectomy after previous hysterectomy can be significantly decreased by using
      the retroperitoneal operative technique and the Endopouch.

PMID- 9026175
TI  - [Treatment of estrogen deficiency-induced sex disorders].
AB  - OBJECTIVE: Is it possible to successfully treat sexual disturbances related to an
      estrogen deficiency syndrome with estrogens? METHODS: For 4 months, sexual
      dysfunctions (loss of libido, dyspareunia, difficulties in experiencing orgasm)
      were treated with a transdermal system-the estrogen patch-in one group cyclically
      and in a second continually. Women with uterus got 1 mg/day norethisterone
      acetate for 12 days a month. RESULTS: By estrogen therapy alone, success was seen
      in 40/41% for loss of libido, in 75/56% for dyspareunia and in 47/25% for
      difficulties of orgasm. CONCLUSIONS: In spite of the complexity of the
      biopsychosocial causes of the sexual disturbances in relation with an estrogen
      deficiency syndrome, the replacement therapy is successful in many cases.

PMID- 9026176
TI  - [Liposarcoma of the uterus].
AB  - Fat cell tumors of the uterus are extremely rare; they occur with an incidence of
      0.03-0.2%. These tumors are almost invariably benign. We present the
      exceptionally rare case of a low-malignant liposarcoma of the uterus. The
      histogenesis of these tumors is not completely clear. In the literature, the
      theory of 'tumor metaplasia', a well-recognized phenomenon, is favored.

PMID- 9026177
TI  - [Birth representation with reference to the magical coriander prescription of
      Codex Vindobonensis 93, fol. 102r, of the Austrian National Library].
AB  - One of the most impressive manuscript illustrations of the medieval history of
      midwifery is found in the Codex Vindobonensis 93, fol. 102r (a manuscript from
      the early 13th century), illustrating a magic prescription of herba coriandrum to
      accelerate childbirth. The composition of the omnibus manuscript is critically
      delineated in its historical context. The illustration, being isolated without
      any obstetrical teaching text, is judged as part of the ancient tradition of
      teaching by images which has no parallel north of the Alps. The different image
      traditions are reflected in the historical use and illustration of the midwifery
      chair, which can be traced back only to the beginning of the 16th century in
      Central Europe and on the British Isles. The importance of the magic prescription
      is shown by comparison within the same and other collections used in the Middle
      Ages and classified in the context of further traditions of magic in midwifery.

PMID- 9026178
TI  - Teen parenting reconsidered.

PMID- 9026179
TI  - [A clinico-pharmacological basis for optimizing the treatment of therapy
      resistant forms of epilepsy].
AB  - On 44 epileptic patients antiepileptic phenobarbital, finlepsin, diphenine,
      hexamidine were studied. The alterations in the level of free and bound fractions
      under the drug application in maximal tolerance daily doses, depending on changes
      in the administration frequency during the day, were recorded. It was established
      that level fluctuations of the total preparation occur mainly owing to level
      alterations in the fraction not bound to serum proteins. An increase in the drug
      administration frequency under the constant daily dose leads to a distinct
      reduction in the free fraction level fluctuations between doses, to a decrease in
      the intensity or removal of side effects, and makes it possible to further build
      up the daily dose to obtain the required effect.

PMID- 9026180
TI  - [Changes in venous tonus in rats with heart failure during acute and chronic
      perindopril administration].
AB  - The effect of chronic administration of perindopril (given per os daily for 21
      days) and a single i.v. injection of perindoprilate (0.5 mg/kg) on the mean
      circulatory filling pressure (MCFP), mean arterial pressure (MAP), and heart rate
      (HR) was evaluated in conscious rats with heart failure caused by embolization of
      the coronary vessels with microspheres 21 days prior to the experiment. In the
      group of rats with cardiac failure perindoprilate reduced MAP by 10% and MCFP by
      15%, but did not change AP and MCFP in animals which had been subjected to a sham
      operation. Perindopryl reduced AP by 41% and MCFP by 20% in rats with heart
      failure, and by 37% and 13%, respectively, in rats which had undergone a sham
      operation. It is concluded that the venous vessels in rats with heart failure
      possess increased sensitivity to perindopril.

PMID- 9026181
TI  - [The effect of antianginal preparations on the hemodynamics and metabolism of the
      ischemic myocardium].
AB  - The effect of nitroglycerin, beta-blockers, and calcium antagonists on the main
      parameters of central hemodynamics and myocardial metabolism is described. The
      original algorithm of the choice of the most effective drug or a combination of
      drugs depending on the initial state of central hemodynamics and coronary venous
      blood flow is presented.

PMID- 9026182
TI  - [The cardiohemodynamic characteristics of the action of obzidan in patients with
      an artificial pacemaker and ischemic heart disease with different types of blood
      circulation].
AB  - The effect of a single administration and a 2-week course of obsidan treatment on
      cardiohemodynamics was studied in patients with an artificial cardiac pacemaker
      and a fixed rate of electrocardiostimulation. Echocardiography showed that
      obsidan reduced heart contractility and pump function in patients with an
      artificial cardiac pacemaker and different types of blood circulation (hyper-, eu
      , and hypokinetic). The cardiohemodynamic effects of obsidan were found to be
      dependent on the initial type of circulation and the features of intracardiac
      hemodynamics in different modes of cardiac pacing.

PMID- 9026183
TI  - [The biological range and characteristics of the importance of adenosine
      receptors for the resistance of the brain to total ischemia].
AB  - In the total brain ischemia the cerebroprotective effect (CPE) of adenosine was
      pronounced in the following order: mouse > rat approximately guinea pig (males >
      females). The sensitizing effect (SE) of theophylline is the same in different
      species but is more pronounced in females compared to males. Newborn rats are
      much more tolerant to the total brain ischemia. The adenosine CPE increases and
      the theophylline SE decreases with age. The adenosine receptor component,
      evidently, contributes greatly to the natural tolerance of newborn animals to the
      total brain ischemia.

PMID- 9026184
TI  - [The antioxidative properties of furosemide in renal ischemia].
AB  - The intensity of lipid peroxidation increases in ischemic damage to the kidneys.
      That furosemide possesses antioxidant properties was established on a model of in
      vitro total kidney ischemia. It is supposed that the protective effect of
      furosemide in ischemic damage is due to inhibition of lipid peroxidation.
      However, such an effect is not encountered in kidney ischemia in an intact
      organism. Furosemide does not prevent the fall of selenium concentration in the
      kidney after ischemia.

PMID- 9026185
TI  - [The efficacy of using alpha-tocopherol during ftorotan anesthesia].
AB  - Halothane monoanesthesia in hypoxia leads to activation of lipolysis with
      increase in the content of NEFA and POL products. The administration of alpha
      tocopherol in a dose of 50 mg/liter in such cases was conductive to a
      statistically significant decrease in the content of peroxidation products in the
      blood.

PMID- 9026186
TI  - [The effect of a peptide preparation made from ovaries on reproductive function].
AB  - A study was done on the action of the low molecular peptide preparation isolated
      from cow ovaries by the acetic acid extraction, on the rat ovary function. It was
      revealed that this preparation: 1) does not possess the gonadotrophic activity;
      2) enhances the sensitivity of immature rat ovaries to the human chorionic
      gonadotrophin; 3) increases the number of ovulating oocytes in neonatal
      androgenized rats in gonadotrophic stimulation of the ovary function; 4) does not
      influence the character and duration of the estrous cycle in intact adult rats.

PMID- 9026187
TI  - [The effect of C-ring transformed estrogens on the reproductive system].
AB  - Comparative study of the effect of two groups of C-ring transformed oestrogens on
      the reproductive system was conducted in experiments on female rats. 11-Nitrate-9
      alpha, 11 beta-dioxyethynylestadiols (I-IV), 11-nitrate-9 alpha-oxyesterons (V
      VII), and 11 formiate-11 beta-oxyethynylstadiol (VIII) were given per os to the
      rats. As compared to ethynylestradiol (EE), compounds I-IV demonstrated 4-10
      times higher oestrogenic activity and 11-23 times higher contraceptive activity.
      11-Nitrate (V-VII) proved to be less active oestrogens (77-91% of EE activity)
      but its contraceptive effect was equal to or exceeded that of EE. The oestrogenic
      activity of 11-formiate (VIII) was three times higher than that of EE, but its
      contraceptive effect was only 50% of the effect of EE. The higher contraceptive
      effect of compounds I-IV in comparison to their oestrogenic activity allows these
      oestrogens to be considered perspective substituents of EE among the oral
      contraceptives. In oral administration of compound I alone or compounds I and IV
      together with gestagen acetomepregenol (AMP), inhibition of luteinizing hormone
      release was stronger and more prolonged than in administration of EE alone or in
      combination with AMP. This effect may be considered to be one of the possible
      mechanisms of the activity of 11-nitrate oestrogens.

PMID- 9026188
TI  - [The early response of the blood lymphocytes in mice to phosphacol and its
      practical significance].
AB  - Phosphacol drops applied to the eye of a mouse caused an immediate response of
      the blood lymphocytes. The number of phosphacol-immune rosette-forming and blast
      forms of lymphocytes increased. The response is specific since the formation of
      rosettes is blocked by the excess of phosphacol in vitro and does not occur when
      rausedyl-sensibilized erythrocytes are used. The formation of blast forms is
      intensified after small doses of phosphacol (10-9), but not rausedyl, are put
      into a suspension of blood cells. The technique proposed may be used for
      determination of phosphorus-containing compounds in the organism and the
      diagnosis of poisoning with them.

PMID- 9026189
TI  - [The late effects of the toxic action of platinum-containing cytostatic
      preparations on rat progeny].
AB  - Experiments on Wistar rats studied the state of the posterity born as a result of
      mating of intact females with males, who were injected with the antitumor drug
      platidiam one month before mating (once, intravenously, maximal tolerance dose).
      The pre- and postimplantation death rate did not grow in female rats mated with
      test males. However, the fetuses showed visceral anomalies and delayed
      development of skeleton. A decrease in the muscle tone, as well as ability for
      the training and extrapolation behavior, were observed in some newborn rat pups.

PMID- 9026190
TI  - [The kinetics of the excretion of a choline-containing polymer from the body of
      rats and its effect on the activity of intestinal enzymes].
AB  - It was shown that the studied choline-containing polymer is practically not
      absorbed in the gastrointestinal tract. It is eliminated mainly on the first day.
      It causes an inhibitory effect on disaccharidases, does not affect animal growth,
      and has no negative effect on food uptake.

PMID- 9026191
TI  - [An evaluation of the chronic toxicity of the new preparation val'kofen for
      children].

PMID- 9026192
TI  - [A comparative pharmacological study of the serotoninergic antidepressants
      tetrindole and fluoxetin].
AB  - Tetrindol, a selective inhibitor of MAOA (predominantly of serotonin oxidase) and
      fluoxetine, an inhibitor of serotonin neuronal uptake, were studied in
      psychotropic tests on mice and rats. Both drugs significantly intensified 5
      hydroxytriptophan-induced head twitching, reduced the effect of reserpine and the
      destructive action of maximal electroshock and the scopalamine-induced transient
      disruption of memory in a test for conditioned response of passive avoidance in
      rats and mice. In a behavioral swimming test the drugs were less active. In
      potentiation of 5-HT activity both drugs were approximately equal.

PMID- 9026193
TI  - [Changes in the morphofunctional status of the liver in rats with acute
      tetrachloromethane poisoning and their correction with antihypoxants,
      antioxidants and actoprotectors].
AB  - The acute tetrachlormethane intoxication leads to structural and metabolic
      alterations in the rat liver. Morphological changes include centrolobular
      necroses and blood stasis in dilated sinusoidal capillaries. Metabolic changes
      are manifested by an increase in the water content and time of the spin-lattice
      (T1) and spin-spin (T2) relaxation (this indicates a lesser degree of water
      structuralization and its enhanced lability), and distortion of the correlation
      between T1 and T2. The prophylactic administration of one of the antihypoxants,
      antioxidants or actoprotectors normalizes the morphofunctional condition of the
      liver. According to the degree of the therapeutic efficacy, the examined
      preparations form the following series: dibunol > gamma-sodium hydroxybutyrate >
      tomerzol.

PMID- 9026194
TI  - [The effect of calcium channel blockers on the effects of ethanol in the
      immobilization of mice].
AB  - A model of the depressive behavior was used to study the action of the calcium
      channel blockers combined with ethanol. The ethanol dose used (2 g/kg, per os)
      caused behavioral changes by the depressive type. From two drugs fendilin (20
      mg/kg) and nifedipine (10 mg/kg) showing the antidepressive activity in the test
      the ethanol effect was counteracted only by the nifedipine. Other drugs, such as
      cinnarizine (50 mg/kg), verapamil (25 mg/kg), flunarizine, and sabeluzol (10
      mg/kg), did not produce a significant effect.

PMID- 9026195
TI  - [Regimens for administering plasminogen activators].
AB  - The results of biochemical and clinical studies of the dosage regimens for
      plasminogen activators were analyzed. The tendency to administer plasminogen
      activators in a bolus was revealed, so as to provide early medical aid and reduce
      the term of infusion to attain complete reperfusion of the occluded vessel. The
      importance of developing plasminogen activators of the next generation by
      chemical and biological synthesis and applying them according to a simplified
      dosage schedule was emphasized. It was pointed out that thrombolytic compositions
      promoting a favorable long-term prognosis in patients with cardiovascular
      diseases must be formed.

PMID- 9026196
TI  - [A method for evaluating the zoosocial behavior of rats in psychopharmacology].
AB  - The method was proposed for experimental assessment of the drug psychotropic
      spectrum in rats under pair interaction conditions. The method was based on the
      recording and analysis of the main behavioral elements with a specially developed
      point scale. A study was done on spectra of the diazepam, amphetamine, and
      desipramine activity. The results of pharmacoethological analysis confirm the
      effectiveness of the proposed method for the assessment of psychotropic spectrum
      of the well known drugs (diazepam, amphetamine, desipramine), as well as new
      pharmacological compounds.

PMID- 9026197
TI  - [Traditional and new methods in the teaching of pharmacology].

PMID- 9026198
TI  - [The microsomal enzyme system and liver pathology].
AB  - The review contains experimental and clinical data concerning diminution of the
      microsomal enzyme system function, in particular the decrease in the content of
      the basic components and activity of microsomal redox chains in different types
      of liver pathology. The molecular mechanisms of the damage and the possibilities
      of pharmacological correction are discussed.

PMID- 9026199
TI  - [The action of piracetam and its complex with sodium oxybutyrate in the
      neuropathic pain syndrome].
AB  - Effects of the pyracetam and its sodium hydroxybutyrate complex were studied on a
      model of the neuropathic pain syndrome. It was demonstrated that the pyracetam
      prevents the development of the neuropathic pain syndrome. The pyracetam relieves
      the pain syndrome. The sodium hydroxybutyrate appears to enhance preventive and
      medical effects of the pyracetam. Possible mechanisms of action of these drugs
      are discussed.

PMID- 9026200
TI  - [The effect of calcium channel blockers on activity in the sympathetic nerves, on
      the vasomotor reflex and on cerebral circulation].
AB  - Experiments on cats showed that calcium canal blockers of the dihydropyridine
      series (nimodipine, nifedipine) and, to a lesser measure diphenylpiperazine
      derivatives increase the activity in sympathetic nerves attributable to the
      central effect of the drugs. Cinnarizine had a diametrically opposite effect.
      Cinnarizine, nimodipine, and nifedipine reduced the reflex pressor response of
      the arterial pressure, whereas flunarizine mainly promoted the vasomotor reflex.
      Therefore, the central stimulating effect of flunarizine dominated over its
      peripheral vasodilative action. Nifedipine caused the most pronounced increase in
      cerebral blood flow, followed by nimodipine, flunarizin, and cinnarizine.

PMID- 9026201
TI  - [The effect of cytochrome c preparations on the autoregulation of the cerebral
      blood flow in ischemia].
AB  - The effect of animal cytochrome C (Ca), biotechnological cytochrome (Cb) and its
      hemtetradecapeptide (HTDP) on cerebral blood flow autoregulation during rapid
      decrease of systemic arterial pressure (SAP) was studied in acute experiments on
      rats. Cytochrome C preparations caused no effect on the autoregulatory responses
      of the cerebral vessels in animals with normal cerebral circulation. Injection of
      5 mg/kg Ca and Cb and 0.8 mg/kg HTDP promoted restoration of the phenomenon of
      cerebral blood flow autoregulation in ischemic brain damage in change of SAP from
      120 to 60 mm Hg. Prophylactic injection of 20 mg/kg Ca and Cb and 3.3 mg/kg HTDP
      prevented cerebral blood flow autoregulation disturbance caused by transitory
      brain ischemia.

PMID- 9026202
TI  - [The effect of verapamil on changes in the Ca2+ content of the intracellular
      structures of organs during acute myocardial ischemia].
AB  - In experiments on rats with acute myocardial infarction induced by occlusion of
      the left coronary artery in conscious animals the protective effect of verapamil
      on the heart, brain, liver, and kidneys in this disease was studied. The
      effectiveness of the drug was judged by the changes in the 45Ca2+ content in the
      intracellular structures (cytosol, mitochondria, endoplasmic reticulum) of the
      organs under study. A single injection of 200 micrograms/kg verapamil in acute
      myocardial infarction reduces considerably the content of 45Ca2+ in the
      intracellular structures of these organs and thus prevents the development of
      pathological processes.

PMID- 9026203
TI  - [The limitation of lipid hyperperoxidation and the prevention of stressor damages
      to the heart by glycine derivatives].
AB  - It is shown that glycine derivatives decrease considerably activation of lipid
      peroxidation in stress, reduce the duration of the alarm stage of the stress
      reaction, and limit the stress damage to the heart. The idea of the organism's
      glycinergic stress limiting system is suggested.

PMID- 9026204
TI  - [The phenomenon of resistance to a thiazide diuretic in acute kidney failure].
AB  - The resistance to hypothiazid (hydrochlorothiazide) during the development of
      acute renal insufficiency (ARI) induced by glycerin injection was studied in rat
      experiments. Natriuretic, kaliuretic, and hydrouretic activity of the diuretic
      decreased two days after injection of a glycerin solution. In this period
      hypothiazid excretion with the urine was least. Ten days later, despite the
      restoration of the water- and electrolyte-excretion function of the kidneys and
      normalization of hypothiazid excretion with the urine, the natriuretic effect of
      the drug was still very poor. This is indirect evidence of the long-term
      affection of the receptors for the thiazid diuretics during the development of
      ARI. The affection remains even after the excretory function of the kidneys is
      restored. The high correlation between the cumulative excretion of hypothiazid
      with the urine and natriuresis encountered in intact animals was weaker in rats
      with acute renal insufficiency.

PMID- 9026205
TI  - [The mechanism of the diuretic action of the preparation polyosm].
AB  - The mechanism of the diuretic effect of the new drug polyosm, polyethylene oxide
      400 solution, was studied in experiments on anesthetized cats. Intravenous
      polyosm infusion was attended with a marked diuretic and natriuretic effect
      developing due to reduced reabsorption of water and natrium and increased
      glomerular filtration.

PMID- 9026206
TI  - [New approaches to determining the type classification of presynaptic
      acetylcholine receptors].
AB  - A complex of special tests which took into account the coupling of the specific
      physiological responses with individual subtypes of muscarinic cholinoceptors,
      and radioligand analysis showed the predominance of M3- and M2-subtype
      presynaptic receptors in the rat brain hemispheres. The autoreceptors regulating
      the presynaptic release of acetylcholine are related mainly to the M2-subtype and
      account for the smaller part of the mixed population of presynaptic receptors.

PMID- 9026207
TI  - [New possibilities for metabolic protection from hypoxia in pregnant rats and
      their progeny].
AB  - Individual resistance of pregnant rats and the newborns to acute hypoxic hypoxia
      was studied. It was found that individual resistance of the organism to hypoxia
      significantly decreases in the last period of pregnancy. A new drug limontar
      proved to possess the properties of an active antihypoxia agent. Its
      administration during the last third of pregnancy stimulated the organism's
      protective-adaptational reactions, increased the resistance of pregnant, rats and
      the newborns to hypoxia. Limontar significantly improves the mechanometabolic
      indices of an isolated perfused heart under hypoxic conditions. Analysis of the
      obtained data suggests that limontar increases energy formation in the myocardium
      through activation of a more efficient and energetically beneficial path of
      succinic acid oxidation.

PMID- 9026208
TI  - [The blood-stimulating properties of lysine baicalinate].
AB  - The possibility of stimulating hemopoiesis inhibited by a single dose (2.0 Gr) of
      total irradiation with Lysini Baicalinatum, a vegetable origin drug, has been
      studied on CBA mice. A 3-fold drug administration (total dose 150 mg/kg) on days
      3, 4, and 5 after irradiation promoted bone marrow erythropoiesis and less
      granulopoiesis. A mechanism of Lysini Baicalinatum stimulating effect is
      connected with intensification of hemopoiesis inducing microenvironment's
      functional activity.

PMID- 9026209
TI  - [The pharmacological blockade of protein glycosylation in diabetes mellitus using
      sulfonylurea derivatives and biguanides].
AB  - A hypothesis is advanced, according to which substances containing an amino group
      can compete with glucose in binding with protein groups and inhibiting in this
      way glycosylation. Screening in vitro experiments with nicotinic acid,
      nicotinamide, piracetam, panangin, ascorbic acid, bucarban, betanase, and adebit
      in a concentration of 10(-3) M were performed. Bucarban, betanase, and adebit
      were found to be capable of inhibiting glycosylation. Daily oral administration
      of bucarban and adebit in therapeutic doses for one month reduced the blood
      fructosamine level in rats with alloxan diabetes without changing the level of
      glycemia.

PMID- 9026210
TI  - [The mechanisms of the interaction of contrast media with serum albumin and gamma
      globulin studied by means of fluorescence extinction and equilibrium dialysis].
AB  - The mechanisms binding X-ray contrast media and magneto-resonance contrast media
      of various structure with human serum albumin and gamma-globulins were studied.
      Equilibrium dialysis showed that X-ray contrast media bind with blood plasma
      proteins, but magneto-resonance contrast media do not interact with these
      proteins. Electrostatic forces play a significant role in formation of complexes
      of X-ray contrast media with human blood serum albumin. With increase in the size
      of the molecule of the X-ray contrast media their affinity for the binding sites
      of this protein diminishes. The formation of complexes of X-ray contrast media
      with human blood plasma gamma-globulins occurs through hydrophobic interactions.
      Increase in the size of the molecules of these media reduces their affinity for
      the gamma-globulin binding sites.

PMID- 9026211
TI  - [Brain glycolipids in rats after disulfiram administration].
AB  - The effect of disulfiram (teturam, antabus) (200 mg/kg, intragastrically) on the
      rat brain glycolipid structure was studied. It was found that disulfiram
      increased the contents of cerebrosides I and III in nervous tissue. The
      administration of alcohol (1 g/kg, 20% solution, intraperitoneally), with
      disulfiram being simultaneously administered, was accompanied by increased levels
      of brain cerebrosides I and II.

PMID- 9026212
TI  - [An experimental study of the effect of Zofran on the manifestations of a primary
      reaction to irradiation].
AB  - Zofran is a selective antagonist of 5-HT3 receptors which effectively prevents
      postradiation dyspeptic and behavioral disorders in dogs and rats. Administration
      of the drug normalizes intestinal absorption and propulsion activity in
      irradiated animals.

PMID- 9026213
TI  - [The hypolipidemic and antiatherosclerotic properties of the ammonium salt of
      glycyrrhetic acid and of 18-dehydroglycyrrhetic acid].
AB  - Plant compounds ammonium salt of glycyrretic acid (AGA) and 18-dehydroglycyrretic
      acid (18-DHGA) effectively reduced the concentration of total cholesterol,
      triglycerides, and atherogenic lipoproteins in blood serum of rabbits with
      modeled cholesterol atherosclerosis. They reduced significantly the content of
      malonic dialdehyde and raised the activity of superoxide dismutase in the
      animals' organs. Due to their powerful hypolipidemic and antioxidant effect AGA
      and 18-DHGA significantly reduced the surface of the atherosclerotic changes of
      the aorta. Both compounds considerably excel polisponin in the indicated
      properties.

PMID- 9026214
TI  - [The effect of amtizol on energy metabolism and lipid peroxidation processes in
      acute hypoxia].
AB  - The effect of amthizol on energy metabolism and lipid peroxidation in the brain,
      heart, liver, kidneys, and skeletal muscles was studied in experiments on rats
      with acute hypoxia (altitude 8,000 m, exposure 30 min). Intraperitoneal injection
      of amthizol (25 mg/kg) 30 min before the development of hypoxia prevented
      disorders of energy metabolism in the organs and inhibited activation of lipid
      peroxidation.

PMID- 9026215
TI  - [The prospects of the search for biologically active substances among
      noncondensed thiazolidones-2].
AB  - The neuroleptic, analgesic, antiinflammatory, antihypoxic, diuretic,
      bacteriostatic, and fungistatic activity of bicyclic noncondensed thiazolidons-2
      with alkylene and aryl bridges was studied. Certain regularities in the relations
      between the structure of the compounds under study and their biological activity
      were found.

PMID- 9026216
TI  - [The stress-protector properties of new analogs of mediator amino acids].
AB  - Stress-protective effect of phosphonglycerid and acyl analogs of neurotransmitter
      amino acids, which displayed nootropic activity was obtained. These compounds
      exerted positive influence on behavioral failure and morphological statement
      after 18-h immobilization. Dilithium-N-acetyl-L-aspartic acid (AKF-94) and di(3
      dimethoxyphosphorylpropyl) ester of N-acetyl-DL-aspartic acid (PIR-87-6-0)
      displayed the most expressive activity. Previously activating influence of these
      compounds at excitatory amino acid transmission had been shown. We supposed
      participation of this way in stress-protective effect of new compounds.

PMID- 9026217
TI  - [Local cerebral ischemia in rats induced by ligation of the middle cerebral
      artery].
AB  - A model of local cerebral ischemia induced by ligation of the middle cerebral
      artery, which is a modification of the techniques proposed by A. Tamura and
      others, is suggested. It allows experiments to be conducted on conscious animals
      with appraisal of the morpho-functional state of the nervous system. Ligation of
      the middle cerebral artery caused a marked decrease (by 85 +/- 9%) in the blood
      flow in the temporal area of the cerebral cortex. The use of this method will
      promote a purposeful search for drugs for the treatment of patients with ischemic
      disorders of cerebral circulation.

PMID- 9026218
TI  - [Devices for measuring the temperature of laboratory animals].
AB  - Three devices for measuring body temperature in small laboratory animals were
      designed: analogous thermometer, temperature-to-frequency converter for digital
      temperature assessment by means of a universal frequency meter and a portable
      digital thermometer providing temperature measurement accurate to 0.1 degree C.
      The devices were tested in experiments on laboratory rats and mice and proved to
      be highly reliable in long-term recording of parameters.

PMID- 9026219
TI  - [Test paper for the primary screening of pharmacological compounds--monoamine
      oxidase inhibitors].
AB  - A method for determining MAO-inhibitory activity of pharmacological compounds is
      described (for primary screening). The advantages of this method are as follows:
      quick analysis, small amount of reagents, visual estimation of the results of
      screening.

PMID- 9026220
TI  - [The binding of drugs with erythrocytes].
AB  - The article reviews the data on the binding of drugs to erythrocytes. Various
      mechanisms of the uptake of drugs by the erythrocytes and the role of the red
      blood cells as carriers of the drugs to the target organs are discussed.
      Significant correlation of the clinical and pharmacological effect of many drugs
      with their content in the erythrocytes is shown. Determination of the
      pharmacological parameters from the content of the drugs in the erythrocytes or
      whole blood rather than in the plasma is recommended.

PMID- 9026221
TI  - [Angiotensin-II receptor blockers in the treatment of arterial hypertension].

PMID- 9026222
TI  - [The influence of calcium channel blockers on antidepressant effects].
AB  - In C57BL/6 mice a combination of nifedipine (5 mg/kg) with imipramine (5 mg/kg),
      amitriptyline (5 mg/kg), pyrazidol (12.5 mg/kg), anafranil (6 mg/kg), and lithium
      chloride (25 mg/kg) diminished the immobilization time. The same was observed
      after treatment with a combination of phendiline (10 mg/kg) with amitriptyline,
      mianserin (3 mg/kg) and alpazolam (0.01 mg/kg). The inhibitory action of diazepam
      (0.5 mg/kg) in this test was prevented only by nifedipine. A depressogenic effect
      of alprazolam was enhanced by verapamil (10 mg/kg) and diminished by phendiline.
      It was concluded that nifedipine and phendiline has significant perspective in
      clinical trials.

PMID- 9026223
TI  - Effects of osmotic stress on metabolism, shape, and amino acid content of
      Leishmania.
AB  - An acute decrease in osmolality causes a rapid change in the shape of the
      parasitic protozoan Leishmania donovani as determined by light microscopy and by
      flow cytometry. Incubation of the cells is an isotonic buffer supplemented with
      glucose. 2-deoxyglucose (2-DG), alanine, or proline also causes a shape change,
      presumably due to the swelling caused by the water that accompanies these
      substrates as they are actively transported into the cells. Hypo-osmolality also
      causes a rapid release of alanine and several other amino acids via a swelling
      activated amino acid channel. A sudden increase in osmolality causes a change in
      shape, an inhibition in the rates of oxidation of alanine, proline, leucine, and
      glucose, and in the rates of uptake of 2-aminoisobutyrate (AIB) and 2-DG. The
      protein kinase inhibitors staurosporine and genistein inhibited the rates of
      oxidation of alanine, glucose, and proline in a culture-age dependent manner and
      also altered the rate of release of AIB in response to hypo-osmotic stress. The
      possible roles of protein kinases in the culture-age dependent changes in the
      uptake, release and metabolism of several amino acids and of glucose are
      discussed.

PMID- 9026224
TI  - [The major outer-membrane protein of Chlamydia: structure and functions].
AB  - This review presents the structure of the major outer-membrane protein of
      Chlamydia and its functions at different levels of the developmental cycle of
      Chlamydia. The antigenicity and the immunogenicity of the protein, which made
      this antigen essential for the establishment of a protective immunity, are also
      presented.

PMID- 9026225
TI  - [Experimental infestation of goats with first instar larvae of Oestrus ovis].
AB  - A protocol of experimental infection with OEstrus ovis larvae L1 was applied to
      kids in order to study their susceptibility to OEstrus ovis. Two-month-old kids,
      born and raised indoors during winter, were infected with single or repeated
      administrations of OEstrus ovis L1. Two or three months later, the kids were
      slaughtered and larvae harvested from their nasal cavities. Following a single
      administration of 30 L1, 8.3 and 3.3% of the larvae survived after two and three
      months respectively. After eight repetitive infections in two months with the
      same number of larvae (30 L1), only 2.2% survived. Over a three months period,
      ie, eleven repetitive infections with a total of 61 L1, only 1.4% were found at
      the necropsies. This experiment indicates that goats are not very susceptible to
      OEstrus ovis infection.

PMID- 9026226
TI  - [Descriptive epidemiology of placental retention in intensive dairy herds in
      Brittany].
AB  - The influences of several risk factors (temporal, mechanical, zootechnical and
      nutritional) on the incidence of placental retention (PR) were tested. The study
      was conducted in Brittany on 5,240 calvings of Black-Pied females belonging to 47
      herds surveyed over a period of four consecutive years. For twin births, the PR
      incidence levels were only decreased in the case of calves born alive. Single
      calvings were associated with PR after more than three artificial inseminations,
      or when stillbirths, dystocia or shortened gestational periods were observed, but
      the frequency varied in relation to calving rank. Increased total amounts of
      concentrate and cake supplied at the end of the gestational period decreased the
      incidence of PR in heifers. Shorter dry periods and high levels of milk
      production increased the risk of PR in multiparous cows. The frequency at which
      PR was observed in both cows and heifers was lower in autumn. Milk production and
      fertility were decreased in animals having experienced PR. In addition, they were
      subject to more uterine disorders than other cows during the subsequent
      lactation, whatever number of calves had been carried. Milk fever in the third
      lactation and metabolic diseases in the fourth were more frequently observed
      following PR.

PMID- 9026227
TI  - [Experimental infection of Glossina morsitans morsitans (Mall) with Trypanosoma
      congolense (ZRE/G143/90). Parasite cycle and vector competence in the tsetse
      fly].
AB  - This report presents an experimental study of the life cycle of Trypanosoma
      congolense (ZRE/G 143/90) in relation to the vectorial competence of Glossina
      morsitans (Mall). The rate of engorgement at the time of an infectious meal and
      the mortality before day 15 of the life cycle were not significantly different
      between male and female flies. The mesocyclic forms of trypanosomes were
      regularly observed in the proventriculus, crop duct, oesophagus, cibarium and
      proboscis, except in the crop. On day 12 of the cycle, epimastigote forms were
      predominant in the proboscis. On day 13 of metacyclogenesis, four out of six rats
      (67%) used for feeding the flies were positive for trypanosomes upon buffy coat
      examination. These results demonstrate the short incubation period of
      trypanosomes in the vertebrate host and precociousness of the vectorial
      competence of some individuals of G m morsitans (Mall). Among the three cyclic
      stages, only the procyclic forms in the intestine showed a significant difference
      between the sexes, the male flies being more infected than the females.
      Metacyclogenesis undergoes three cleavages leading to the successive and
      permanent establishment of the procyclic, mesocyclic and metacyclic forms in the
      midgut, proventriculus and proboscis respectively.

PMID- 9026228
TI  - [Comparison of orthotopic neobladders: Studer vs modified Camey II].
AB  - A comparative study between modified Camey II and Studer ileal orthotopic
      neobladder was performed. The Camey II was modified as follows: 1) The ureters
      were implanted, using wallace technique, in an undetubularized ileal loop, 15-18
      cm. long, to prevent vesico-ureteral reflux; 2) The neobladder was made using
      staplers. In such a way, time is saved (about one hour) and results are quite
      similar, with a low rate of ureteral stenosis in both groups.

PMID- 9026229
TI  - [Orthotopic ileal neobladders in men and women: techniques and comparison].
AB  - PURPOSE: evaluation of results and complications of ileal orthotopic neobladders
      in men and women with transitional cell carcinoma. MATERIALS AND METHODS: between
      12-89 and 12-95 we performed 146 radical cystectomy for bladder neoplasm, in 32
      patients we can perform ileal orthotopic neobladder, 29 were male and 3 were
      female. Oncologic indications to this kind of operation were: clinical stage T2,
      T3a, T3b, T1G3 multicentric and or recurrence, absence of metastasis absence of
      nodal metastasis, negativity of urethral biopsy. General contraindications were
      urethral stenosis and incontinence. Oncological contraindications, in woman, were
      bladder neck neoplasm or urethral neoplasm. In 4 patients we use Camey II
      technique, in 19 pts we performed the paduan ileal neobladder, in 9 pts we use
      Hautmann technique. 7 patients performed neoadjuvant chemotherapy with 4 circles
      of MVAC, 4 pts underwent adjuvant chemotherapy, and 2 pts salvage chemotherapy.
      In woman we take care during cystectomy to dissect cardinal ligament very close
      to cervix uteri, to resect the uterosacral ligament far to the sacrum. We did not
      dissect under the ureter and we cut the urethra 0.5-1 cm far from the bladder
      neck. RESULTS: follow up was between 6 and 66 months. 24 patients are now alive
      and disease free, 2 patients are alive with disease progression, 1 have a pelvic
      recurrence and 1 have pulmonary recurrence. 4 pts died for disease progression
      and 2 for non oncological cause, quality of life was considered as regard to
      continence and sexual activity. 1 pts was completely incontinent and 1 pts has
      nocturnal incontinence with a daily micturation every 1 hour. We can evaluate
      only 18 patients for sexual activity and 4 reported normal erection.
      COMPLICATIONS: in three cases we had to reoperate for early complications due to
      mechanical bowel obstruction, ileocutaneous fistula and wound dehiscence. In
      three cases we had the formation of stones, in two patients ureteroileal
      stenosis, in two cases urethro-ileal stenosis and 1 reflux from the neobladder.
      Orthotopic ileal neobladder allows a very good quality of life and is the first
      choice derivation after radical cystectomy.

PMID- 9026230
TI  - [Orthotopic urinary diversions: the Paduan ileal neobladder. Experience at the
      Urologic Division of Magenta].
AB  - We refer our experience about continent ileal orthotopic bladder in male patient
      with bladder tumor we report our selections criteria, with particular attention
      about technical point of view. We show the results, early and late complications.

PMID- 9026231
TI  - [Urodynamic evaluation of replacement bladders (Mainz)].
AB  - 42 ileo-colonic orthotopic reservoirs (M.A.I.N.Z.) following radical cystectomy
      were evaluated with urodynamic studies. Long term results in 19 patients with a
      follow up longer than 36 months were compared to the findings of 23 patients with
      a shorter follow-up. Urodynamic evaluation showed a reservoir with large capacity
      and low pressure in both groups. Nocturnal incontinence occasionally occurred.
      Many factors may account for this problem. Instillation of hyperosmotic solution
      during cystometry resulted in increased amplitudes and frequency of intracavitary
      pressure waves: the nocturnal increase in urine osmolality could be in
      correlation with nocturnal incontinence.

PMID- 9026232
TI  - [Replacement bladders in Oltrepo].
AB  - In our Department we performed 269 radical cystectomies from January 1985 to
      April 1996. As regard the urinary diversion 64 patients were undergone to a
      cutaneous ureterostomy; in 137 we performed a Wallace uretero-intestinal
      anastomosis; in 6 a Mauclaire rectal diversion; in 12 patients a Mainz Pouch II
      and 50 selected patients (44 man and 6 ladies) we performed a Vesica Ileale
      Padovana (VIP). In these cases the stage was lowly, good renal function, no are
      hydronephrosis. The patients were motivated for a long follow-up and
      preoperatively undergone to urethral biopsies. We have had the following
      complications: an early bowel obstruction, 4 wound infections and for the long
      term follow-up 2 inguinal hernias, 1 laparocele, 5 patients with bilateral
      hydronephrosis. At the moment we cannot state a correct oncological report for
      the short follow-up: only 1 patient died after 18 months for a pelvic relapse. We
      can suggest that VIP is a good solution for the ladies: its mandatory to take
      care of the urethra and the pelvic floor for a good continence limiting the
      lymphadenectomy. We haven't any suggestions about the deep of the colpectomy and
      the opportunity of the vaginal suspension.

PMID- 9026233
TI  - [Replacement neobladders in men and women: our experience].
AB  - We present our clinical and metabolic follow-up data of 74 patients submitted to
      total bladder substitution using an ileal orthotopic neobladder in one group of
      64 patients and a continent stomal pouch in another group of 10 patients. In the
      first group the mean follow-up was 41.5 months. The daytime continence was early
      achieved in 89% (57/64) and was maintained with time; at 12 month follow-up
      nocturnal continence was reached in 71% (45/64). Post voiding residual was
      significant only in 4 patients (2 men and 2 women). No clinical signs of
      pyelonephritis nor renal scars at IVP was evidenced in all but 7 patients in
      which a silent uretero-ileal stenosis developed. No severe metabolic acidosis or
      B 12 deficiency occurred. In the second group (Continent Pouch) the long term 3
      Year follow-up shows a complete continence in all patients with an average
      capacity of 600 cc. No late complications occurred in all patients but one in
      which self intermittent catheterization was uncomfortable and now he prefer
      permanent catheter and in another patient with a stone in the Pouch treated with
      Lithoclast. In conclusion, total bladder substitution after radical cystectomy is
      now represented by orthotopic neobladder or continent Pouch in men and women.
      Early and late complication rate is relatively low and continence generally good.

PMID- 9026234
TI  - [Stents in the treatment of stenosis of the entero-urethral junction in continent
      diversion: case reports].
AB  - Strictures of entero-urethral anastomosis in orthotopic neobladder and of the
      catheterizable conduit in continent diversion after cystectomy are seldom
      encountered; they are usually treated with dilation, TUR or cold incision. 3
      cases that came to our observation are presented. The first was treated with TUR
      after neo-bladder neck stricture in orthotopic neobladder; total incontinence
      occurred after this procedure. The patient at present is waiting for AS800
      artificial sphincter implant. The second patient had similar features. After
      repeat TUR a prostacoil removable stent was placed through the stricture and
      removed after 5 months. At 12 months from removal the patient is continent and
      doesn't present clinical evidence of restriction. The third patient underwent
      cystectomy with Indiana continent pouch. After 4 months increasing problems in
      self catheterization occurred due to stricture of the catheterization conduit
      (appendix). He was treated twice with cold incision with early recurrence of the
      stricture. A permanent Memotherm stent (indicated for urethral strictures) was
      placed inside the appendix. After one month self catheterization was started
      again. At a 2 months follow up there is no evidence of stricture. In our
      experience, even if anecdotal, we have verified that treatment of this kind of
      strictures with TUR can cause incontinence or expose to further recurrences. 2 of
      the cases presented were treated with different kind of stents; the outcome is
      good even if the follow up is still short. We believe that this kind of treatment
      can be considered in selected cases.

PMID- 9026235
TI  - [100 orthotopic neobladders in men after cystectomy: a 5-year experience].
AB  - Urethral bladder substitution is traditionally suggested to good prognosis
      cystectomized patients. In our series this diversion was chosen for all but the
      salvage cystectomized men. Between the 1st of February 1991 and the 30th of April
      1996, one hundred consecutive men underwent lower urinary tract reconstruction
      after radical cystoprostatectomy for bladder cancer. An orthotopic ileal
      neobladder was constructed (in 84 cases according to Kock's technique and in 16
      to Studer's technique). Total early complication rate was 29% (29/100), including
      one perioperative death due to sepsis (mortality rate 1%). 13 patients required
      surgery (6 retroperitoneal hematomas, 2 wound dehiscences, 1 urinary fistula, 1
      lymphocele, 1 rectal-neobladder fistula, 1 rectal-cutaneous fistula, 1 necrosis
      of the terminal ureter). The late complication rate was 19% (19/100); in 8 cases
      reparative surgery was required (1 mechanical ileus, 2 bladder neck stenoses, 3
      stenoses of the ureteral anastomosis, 2 laparoceles). Four patients were lost at
      the follow-up; out of the 96 remaining patients only 85 were evaluable for
      continence: continence during the day was achieved in a period between there to
      six months in 78 patients (91.7%); night continence was achieved with planned
      awakenings in 60 patients (70.5%). Eight patients recovered potency, another 7
      had successful intercourses after PGE1 intracavernous injection. Renal function
      based on creatinine value was mildly impaired in 5/78 evaluable patients (6.4%)
      (peak creatinine 2.8 mg%). In 29 patients tumour progression was observed (29%):
      9 pelvic and 20 metastatic. Among the latter 2 urethral recurrences were observed
      (2%). Twenty-four patients died for metastatic cancer, one for primitive lung
      cancer, one patient for postoperative septic shock. Adjuvant chemotherapy was
      administered in 11 patients without complication with an indwelling catheter in
      the neobladder to avoid drug reabsorption. Four patients showed complete response
      (2 are alive after a mean of 12 months), 6 were non responders and 1 had a
      partial response. In our series the ileal neobladder is a feasible method of
      urinary diversion when urethral cancer involvement is ruled out. Early and late
      complications are proportionally decreasing with experience and overall
      continence is satisfactory. The fate of the neobladder depends on both the
      technique and patient's compliance. Only educated patients can cope successfully
      with neobladder diversion without major complications. All the patients operated
      for non salvage cystectomy deserve to be diverted with a continent urethral
      bladder substitution.

PMID- 9026236
TI  - [Orthotopic ileal neobladder: urodynamic and metabolic aspects. Our experience].
AB  - We subjected to a functional and metabolic evaluation (urodynamic examination +
      cystography) 10 patients underwent to radical cystectomy with a ileal orthotopic
      reservoir (VIP) for bladder cancer. At the moment patients have a minimum 3-years
      follow-up and they are out of disease. The medium capacity of the reservoir is
      about 447 ml, with a low pressure flow, a medium pressure of ureteral closing of
      62.5 cm of H2O. At the cystography neither ureteral reflux nor post miction
      residuum have been proved. All the patients are continent, with the exception of
      one patient suffering from episodes of nocturnal enuresis. The metabolic
      evaluation hasn't proved substantial changes except the presence of
      hypocitraturia in the only patient in metabolic acidosis. In conclusion the ileal
      orthotopic reservoir showed a good long-term functionality without considerable
      complication of metabolism.

PMID- 9026237
TI  - [Orthotopic ileal neobladder of the Emikock type: technical points and functional
      results].
AB  - Ileal orthotopic neobladder represents, nowadays, the best urinary diversion
      after cystectomy. Emikock procedure was performed, in our institution, in 26
      patients with bladder cancer T2-T4. At 6-60 months of follow-up 3 pts were died
      with local or at distance neoplastic recurrence, 2 were alive with neoplasms and
      21 were NED. Nocturnal continence was good in 22 cases (88%) and only 3 patients
      were obstructed because of pseudodyssynergia in 2 and stricture in 1. Emikock
      neobladder even if needs a longer surgical time than other procedure and a long
      ileal tract is almost free from severe metabolic disorders. This technique offers
      a good protection of high urinary tract because of antireflux nipple and avoid
      the uretero-intestinal stricture. It not feasible, now, to know the functional
      trend of this reservoir on the long term. Adequate postoperative training is
      recommended to avoid the pseudodyssynergia and functional obstruction of
      reservoir.

PMID- 9026238
TI  - [Ileal neobladder in women: Milano's technique].
AB  - In the female patient with transitional cell carcinoma the risk of urethral
      recurrence is very low, when the bladder neck is histologically free of tumour.
      On the other hand urinary continence can be maintained if the lower half of the
      urethra together with the nerve supply is preserved. On this basis orthotopic
      bladder reconstruction was applied also in a female patient. In order to preserve
      urinary continence minimal dissection was performed anterior to the proximal
      urethra; in addition pubourethral ligaments were left intact. On the other hand
      to prevent chronic urinary retention arising from downward displacement of the
      reservoir a colposacropexy was performed. At 3 weeks the filling cystogram
      demonstrated a well shaped and compliant reservoir. No downward displacement of
      the reservoir was observed in upright position. Neither reflux nor residual urine
      could be demonstrated by voiding cystourethrogram. The woman achieved diurnal and
      nocturnal continence at 3 month.

PMID- 9026239
TI  - [Epidemiological and etiological aspects of excretory azoospermia].
AB  - The average spermatozoa concentration in the ejaculate fell progressive even if
      sharply in the last 50 years. The azoospermia, described as the complete
      spermatozoa absence in the sperm, has a variable incidence between 10 and 20% in
      the clinical picture of the male infertility. The authors outline an etiological
      classification of the azoospermia and analyse the epidemiological and etiological
      aspects of the obstructive azoospermia.

PMID- 9026240
TI  - [Seminal obstructions of the inflammatory origin].
AB  - Presence of bacteria in the sperm is often associated to a reduction of fertility
      in relationship with a decrease in number and motility of spermatozoa and with an
      augmentation of the abnormal spermatic cells. In the most severe cases, chronic
      and complicated phlogosis may lead to obstruction of seminal pathways with
      consequent azoospermia. Clinical features of seminal phlogosis are extremely
      variable both in acute and chronic evolutions. In every case the first
      diagnostical step is sperm count and seminal complete analysis which can give
      evidence of phlogistic alteration in quantity and quality of spermatic cells with
      a typical presence of an excess in white blood cells (leukospermia) as
      consequence of infection. The great variety in clinical and bacteriological
      aspects and the particular biological features of the organs involved, as the
      prostate, makes treatment a difficult problem to solve with particular regard to
      the choice of an effective antibiotic which pharmacokinetic has to result
      suitable for the microorganism as well as for the tissue of the infection site.
      All those efforts are indispensable to reduce the too frequent therapeutical
      failures in the management of seminal phlogistic pathology with complications of
      organic but also physiological relevancy for the patient and the partner too,
      such as azoospermia.

PMID- 9026241
TI  - [Obstructive azoospermia and malformations of seminal tract].
AB  - About 10% of the cases of male infertility is represented by the obstruction of
      the seminal tract, which may be congenital or secondary to inflammatory events or
      surgery. The most frequent obstructive malformation of the seminal tract is the
      bilateral agenesia of the vas deferens. Such malformation is typical of the
      cystic fibrosis (CF), an autosomal recessive disorder determining chronic
      respiratory infections with bronchiectasia, and pancreatic failure. Recently the
      defective gene responsible for CF has been identified on the long arm of the
      chromosome 7. Congenital bilateral absence of the vas deferens (CBAVD) may be
      present in otherwise healthy males without clinical evidence of CF. Genetics
      studies demonstrated that most CBAVD display at least one detectable CF mutation,
      therefore this disease can be considered as an incomplete clinical form of CF.
      With the realization that a man with CBAVD may have CF, albeit a genital form,
      considerable care is required not only to document his specific mutations, but
      also to test his partner for CF mutations to evaluate the risk that their child
      would have CF. The association of chronic suppurating respiratory disease with
      obstructive azoospermia characterizes also the Young's syndrome. In this disease
      the obstruction could possibly be the result of defective epididymal sperm
      transport, related to an abnormality in the mucus. Despite some clinical common
      aspects, CF and Young's syndrome are two distinct entity. In fact, no CF
      mutations have been demonstrated in Young's syndrome. Congenital obstructive
      abnormalities of the vas deferens and epididymis are often associate to
      cryptorchidism (36-68% of the cases) and to patent processus vaginalis. The
      degree of testicular retention and processus vaginalis closure correlates well
      with the incidence of associated epididymal defects. Rare causes of congenital
      obstructive azoospermia are represent by the cyst of Mullerian or Wolffian
      origin. An obstruction to the progression of the sperm along the seminal tract
      can also be present in complex malformations, such as pseudohermaphroditism in
      which the infertility has a multifactorial etiology.

PMID- 9026242
TI  - [Iatrogenic obstructive azoospermia].
AB  - Obstructive azoospermia is a common cause of sterility in men. In the past
      infection played an important role in the aetiology of obstructive azoospermia.
      Recently, however, the aetiology of obstructive azoospermia appears to be
      changing. So iatrogenic obstructive azoospermia has reached an important role in
      the field of obstructive azoospermia. In this work we show international
      literature about iatrogenic obstructive azoospermia. Unfortunately it is poor, in
      spite of an interesting item. We divided iatrogenic obstructive azoospermia into
      six groups, considering the possible anatomical site of obstruction. So we show
      the possible damages at the different levels: testis, epididymis, vas deferens,
      seminal vesicles, prostate and ejaculatory ducts.

PMID- 9026243
TI  - [Obstructive azoospermia. Instrumental diagnosis: echography and endoscopy].
AB  - Obstructive disorders of seminal tract are mainly distinguished in Proximal and
      Distal Obstructive Syndrome, following typical seminal pattern. Fine localization
      of obstruction is very important for prognostic and therapeutic evaluation. In
      Proximal Obstruction the role of echography and endoscopy is today poorly defined
      and usefull. In Distal Obstruction a preeminent role is recognised to transrectal
      ultrasound and its mini-invasive applications: biopsy, evacuative puncture,
      direct contrastography of obstructed seminal way. At this regard is reported a
      case of dysmorphic congenital obstruction documented with transrectal ultrasound
      and contrastography. Diagnostic endoscopic indications mainly refer to
      therapeutic procedures.

PMID- 9026244
TI  - [Role and current significance of EDVG (epididymography plus vasography) in
      obstructive azoospermia].
AB  - The Authors present their 20 years experience about 612 EDVG (epididymography
      plus vasography). We will here discuss indications, complications and future
      prospects of EDVG and refer data arising from 55 andrology units: we can
      appreciate as this methodic is up to date in selected cases, i.e. obstructive
      azoospermia associated with normal FSH levels and lower or absent fructose, in
      presence of clearly pathological TRUS.EDVG is also indicated when on obstructive
      pathology is suspected to be the cause of an oligospermia or before vaso
      vasostomy.

PMID- 9026245
TI  - [Nonsurgical and endoscopic therapy in obstructive azoospermia].
AB  - The endoscopic therapy has an elective role in the distal obstructive azoospermia
      for urogenital carrefour pathologies both organics and functional and differently
      in the resection and/or aspiration with sperm recovery forms. Resolutely attends
      to the symptomatology and positively to the fertility re-establishment, in front
      of a short sickness-rate. The Authors describe the different techniques with
      relative indications, results and complications. Instead medical therapy has a
      role in the obstructive above all post infection and post inflammatory lesions
      prevention. Furthermore propose to oneself the goal to improve the seminal
      quality by the improvement of the semen fertilization capacity and to reduce the
      affections symptomatology. Finally concurs with the sperm selection techniques to
      fertility potential wealth.

PMID- 9026246
TI  - [Surgical therapy of obstructive azoospermia: microsurgery].
AB  - Microscopic procedures for therapy of obstructive azoospermia or of vasectomy
      reversals have resulted in accurate reapproximation of ductal structures. The
      success of vasovasostomy appears to be influenced by the length of time that has
      passed since the vasectomy was performed or the obstruction become. Failures of
      vasovasostomy may be attributed to anastomotic stenosis, sperm antibodies,
      epididymal dysfunction, or an unrecognized epididymal tubule blowout with
      subsequent obstruction. The latter condition should by suspected when, at the
      time of the initial vasovasostomy, there is lack of fluid containing spermatozoa
      in the cut end of the testicular portion of the vas. Chronic intratubular
      pressure may cause an epididymal blowout, with subsequent spermatic granuloma and
      obstruction in the epididymal tubule, that may also be related to a congenital
      disorder or a postinflammatory condition. Spermatozoa gain maturation and the
      capacity for motility as they move from the caput to the cauda of the epididymis
      as possible. Microsurgery allows direct microtubular anastomosis between the
      epididymal tubule and the cut end of the vas. Some conditions are not amenable to
      conventional surgical techniques, such obstructed azoospermia due to congenital
      bilateral absence of the vas deferens or to severe damage to the reproductive
      ducts. To treat these patients surgeons have devised reservoirs (artificial
      spermatoceles) to collect spermatozoa to be used for artificial insemination. An
      alternative treatment method for obstructed azoospermia is to obtain sperm from
      the epididymis with the use of an operating microscope. Although sperm have been
      obtained the poor sperm motility requires either in vitro fertilization or GIFT.
      The technique looks promising, although improved techniques to enhance the
      motility of the collected sperm will ultimately yield better results.

PMID- 9026247
TI  - [The effect of generalized seizures on the structure of the circadian wakefulness
      sleep cycle and on the EEG of rats with a hereditary predisposition for
      audiogenic convulsions].

PMID- 9026248
TI  - [Methylation changes in brain DNA during immobilization stress in rats].

PMID- 9026249
TI  - [The individual typological characteristics of the EEG correlates of human
      emotional reactions].

PMID- 9026250
TI  - [Operant behavioral disorders in monkeys with an MPTP-induced Parkinson-like
      syndrome].

PMID- 9026251
TI  - [Electrophysiological research on the topography of the axodendritic synapses of
      Retzius' neuron in the leech].

PMID- 9026252
TI  - [Metal microelectrodes and their modules for research on the spatial organization
      of the activity in screened brain structures].

PMID- 9026253
TI  - [The effect of CO2 on the blocking of excitation conduction by local anesthetics
      in feline A-delta and C fibers].
AB  - The data obtained showed that the CO2 potentiated the conduction blockade of the
      saphenous nerve with tertiary amine trimecaine in anesthetised cats. The data
      suggests that acidification of cytoplasm with increased CO2 increases the
      concentration of active cationic protonated forms of a local anesthetic agent.

PMID- 9026255
TI  - [The effect of striatal damage on cardiointervalogram dynamics and its circadian
      fluctuations in rats].

PMID- 9026254
TI  - [GABA-immunoreactive structures in the stellate and superior cervical ganglia of
      the cat].
AB  - GABA-immunoreactive point structures and fibers were found in the cat stellate
      and superior cervical ganglia, their diameter varying from 0.5 to 5.0 mcm. GABA
      immunoreactive cells were only found in the stellate ganglion. Character of these
      cells as well the origin of the GABA-immunoreactive fibers, are discussed.

PMID- 9026256
TI  - [AChE-positive neurons in the mammalian stellate ganglion].

PMID- 9026258
TI  - [The morphology and reactive changes in neural structures during chemical
      sympathectomy].

PMID- 9026257
TI  - [The participation of the serotonin link in the neurochemical mechanism of
      transcranial electroanalgesia].
AB  - Metergoline and 5, 7-dihydroxytryptamine were found to suppress and to prevent an
      electroanalgesic effect, resp. An increase in the serotonine contents in the CSF
      after electroanalgesia suggests an activation of the brain serotoninergic system.
      DL-5-hydroxytryptophan and allopurinol enhanced the electroanalgetic effect. The
      data obtained suggests an existence of a serotoninergic component of the
      transcranial electroanalgesia mechanism.

PMID- 9026259
TI  - [The formation of cardiac-electric-field potentials on the surface of the heart
      and torso in vertebrate animals].
AB  - The comparative electrophysiological study of excitation process in heart with
      different types of organization have laid the foundation for solution of the
      problems of formation of cardioelectric field. It was shown, that the form of
      extracellular potentials on the epicardium correlated with different types of
      ventricle myocardial activation. Animals with the "flash" type of myocardial
      depolarization in most cases have the negative extracellular potentials in the
      greater part of the epicardial ventricular surface. Animals with the consecutive
      type of myocardial activation--the positive and biphase potentials. All
      myocardial layers (epicardial, intramural and endocardial) are
      electrophysiologically informative.

PMID- 9026260
TI  - [The correlation of cardiac mechanical activity and arterial pressure in the
      hemodynamic postural reactions of rats].
AB  - In orthostasis, an increase in the body incline angle led to a decrease in the
      systolic AP, systolic pressure in the left ventricle and a progressive decrease
      of the final diastolic pressure in rats. The same incline in antiorthostasis
      decreases the systolic AP, increase the systolic and final diastolic pressure in
      the left ventricle. These and some other findings show that compensatory
      responses are mainly manifested in the vascular system both in ortho- and
      antiorthostasis, whereas shifts in the cardiac activity correspond to the type of
      blood redistribution.

PMID- 9026261
TI  - [Circadian changes in the levels of sex and glucocorticoid hormones in the
      peripheral blood plasma of female silver foxes].
AB  - Domesticated and wild silver fox vixens were shown to differ in their diurnal
      contents of cortisol and progesterone in the blood plasma. The data obtained
      reveal that domestication of silver fox vixens modifies their diurnal rhythms of
      the adrenocortical steroid activity.

PMID- 9026262
TI  - [The effect of the blood flow rate on blood heat emission in the vascular bed of
      the skin].

PMID- 9026263
TI  - [The effect of age, sex and prenatal exposure to glucocorticoids on the
      corticosterone level of the blood in rats].

PMID- 9026264
TI  - [The lateralization effect of oxytocin on the functional activity of paired
      visceral organs in rats].
AB  - Following unilateral intranasal oxytocin administration, asymmetric alterations
      in some functional parameters of the adrenal glands, testis, lungs and heart,
      occurred. The lateralization of alterations was dependent on the side of oxytocin
      injection and the side of paired organ arrevgenent. Possible pathways of
      intranasal oxytocin administration effects on visceral organs as well as causes
      of their asymmetry, are discussed.

PMID- 9026265
TI  - [Early chemical sympathectomy and the function of the hypophyseal-gonadal system
      in sexually immature and adult female rats].
AB  - Early chemical desympathisation with 6-hydroxydopamine decreased the contents of
      the follicle-stimulating hormone in the blood serum of 1-month old rats. The
      steroidogenesis disturbances were more obvious in sexually immature rats in the
      general desympathisation. In sexually mature rats, these disturbances
      disappeared. Sympathetic innervation seems to play a major part in development of
      the reproductive system in rats.

PMID- 9026266
TI  - [Monitoring brain PO2 as a means of predicting brain PN2 changes under hyperbaric
      oxygenation simulating free-floating conditions].
AB  - In rabbits, rats and mice, the delays of maximum of the brain oxygenation curves
      in respect to the maximum pressure curves were found to be 47.4 +/- 5.5 s; 32.6
      +/- 2.9 s; and 26.4 +/- 2.0 s, resp. The data obtained shows the brain
      oxygenation monitoring to help to predict the nitrogen tension dynamics in the
      "fast" tissues during simulation of free surfacing.

PMID- 9026267
TI  - International code of ethics for midwives: how do they fit your practice?

PMID- 9026268
TI  - Effects of 2 years' treatment of osteoporosis with 1 alpha-hydroxy vitamin D3 on
      bone mineral density and incidence of fracture: a placebo-controlled, double
      blind prospective study.
AB  - A two-year double-blind study monitored and evaluated the effects of 1 alpha
      hydroxy vitamin D3 (1 alpha(OH)D3) on the lumbar (L2-4BMD) and total body bone
      mineral densities (TBBMD) and occurrence of fracture in 113 female osteoporotic
      patients receiving 0.75 micrograms/day of 1 alpha(OH)D3 (n = 57) or a placebo (n
      = 56) with calcium supplementation in both groups. L2-4BMD increased 1.81.% and
      2.32% after one and 2 years in the 1 alpha (OH)D3 group, but decreased 1.89% (P <
      0.05) and 0.28% in the placebo group. A significant difference (P < 0.01) existed
      between the two groups after one year. TBBMD decreased significantly in the
      placebo group by 3.34% (P < 0.01) and 3.52% after one and 2 years. Six new
      fractures occurred in the control group, but only two in the 1 alpha(OH)D3 group
      (Odd's ratio = 0.343, 95% confidence range; 0.0648-1.815). There were no serious
      adverse effects of the 1 alpha(OH)D3 treatment. It was concluded that two-year
      treatment with 1 alpha(OH)D3 increased the lumbar BMD and inhibited the decrease
      in TBBMD. Although it was not significant, new fracture occurrence in the 1
      alpha(OH)D3 group was around 1/3 of that in the control group.

PMID- 9026269
TI  - Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBP-1, -2 and -3)
      in diabetic pregnancy: relationship to macrosomia.
AB  - To evaluate the role of insulin-like growth factors (IGFs) and IGF-binding
      proteins (IGFBPs) in excessive fetal growth (macrosomia) in diabetic pregnancy,
      84 insulin-treated diabetic mothers and their infants were tested for serum
      concentrations of IGF-I, IFG-II, and IGFBP-1, -2 and -3. These parameters were
      correlated with the birth weight of neonates and placental weight. IGF-I and II
      levels were determined by specific radioimmunoassays (RIAs) after serum samples
      were extracted with aid-ethanol. IGFBPs were measured by Western immunoblot with
      specific antibodies to the respective IGFBP species. Serum concentrations of both
      IGF-I and IGF-II in mothers with either IDDM or NIDDM increased with the
      gestational period, reached a plateau at the third trimester, and returned to non
      pregnant levels within 7 days after delivery. These values were not different
      from those in normal mothers before and throughout pregnancy. As previously
      reported, IGF-I concentrations in cord serum of neonates born to diabetic mothers
      were (P < 0.01) higher than those of newborns of normal mothers. Likewise, cord
      blood IGF-II levels were 2-fold higher in babies of diabetic mothers (P <0.001).
      Fetal IGF-I and IGF-II correlated with each other and with maternal HbA1C, and
      they positively correlated with either birth weight or placental weight. Cord
      IGFBP-3 concentrations were significantly higher in diabetic pregnancy, but IGFBP
      2 concentrations were not different from those in normal pregnancy. Cord IGFBP-1
      concentrations were significantly higher only in babies of mothers with IDDM.
      None of these cord IGFBP concentrations correlated with birth weight or placental
      weight. The data suggest that fetal IGF-II, like IGF-I, is involved in fetal and
      placental growth in diabetic pregnancy. The role of IGFBPs remained to be
      determined.

PMID- 9026270
TI  - Hypothalamic-pituitary-adrenal axis in WBN/Kob rats with non-insulin dependent
      diabetes mellitus.
AB  - In an attempt to define the hypothalamic-pituitary-adrenal (HPA) axis in non
      insulin dependent diabetic rats (WBN/Kob), we measured plasma corticotropin
      releasing factor (CRF), as well as arginine vasopressin (AVP), ACTH, and
      corticosterone (B), CRF concentrations in the median eminence (ME), the remainder
      of the hypothalamus (rHY) and the neurointermediate lobe of the pituitary (NIL).
      We also measured Iodine-125-labeled ovine CRF ([125I]oCRF) binding in the brain
      and peripheral tissues. Body and thymus weight in WBN/Kob rats were significantly
      lower than in control Wistar rats, but adrenal weight was higher in WBN/Kob rats.
      Plasma ACTH levels were significantly higher in WBN/Kob rats than in the control
      rats. However, plasma CRF, AVP and B levels in WBN/Kob rats were not different
      from those in the control rats. The CRF concentration was significantly decreased
      in the ME of the diabetic rats, compared with control rats, but CRF
      concentrations in the rHY and NIL were unchanged in the two groups. A significant
      reduction in [125I]oCRF binding in the anterior pituitary was demonstrated in
      WBN/Kob rats, but no significant difference between the diabetic and control rats
      in CRF binding was observed in the frontal cortex, spleen or adrenal gland. These
      findings suggest that the HPA axis is chronically stimulated in the non-insulin
      dependent diabetic rats.

PMID- 9026271
TI  - Differential changes of corticotropin releasing hormone (CRH) concentrations in
      plasma and synovial fluids of patients with rheumatoid arthritis (RA).
AB  - Corticotropin releasing hormone (CRH) and ACTH concentrations in plasma and CRH
      and IL-6 concentrations in synovial fluid in patients with rheumatoid arthritis
      (RA) were examined to clarify the relationship between cytokines and the
      hypothalamic-pituitary-adrenal axis (HPA axis). Concentrations of serum amyloid A
      protein (SAA), one of the acute phase proteins, were also measured as an
      indicator of inflammation. CRH and IL-6 concentrations in synovial fluid were
      higher in RA patients than in control patients (osteoarthritis, OA). Plasma ACTH
      and CRH levels were significantly lower in RA patients than in OA patients. This
      suggests that CRH secretion in synovial fluid is regulated differently from
      plasma CRH secretion, as CRH levels in synovial fluid and plasma showed opposite
      changes in RA patients. SAA levels were positively correlated with the levels of
      CRH or IL-6 in synovial fluid, whereas there was no correlation between CRH and
      IL-6 levels. The results suggest that CRH and IL-6 play important independent
      roles in producing SAA in synovial fluid.

PMID- 9026272
TI  - [Need for knowledge and ethics].

PMID- 9026273
TI  - [Is benign breast disease a contra-indication to hormone replacement therapy?].

PMID- 9026274
TI  - [Biweekly menopausal substitutive hormone therapy: effects on climacteric and
      prevention of osteoporosis].

PMID- 9026275
TI  - [Value of cardio-respiratory tests associated with plethysmography and monitoring
      of nocturnal erections].

PMID- 9026276
TI  - [Intra-uterine inseminations with hyperstimulation in male infertility].
AB  - Our aim is to evaluate the efficacity of intrauterine insemination in male
      infertility after controlled ovarian hyperstimulation. 96 cycles were carried
      out. 16 pregnancies were achieved, the pregnancy rate per cycle is 16.7% (43.3%
      per couple) and 12.5% ongoing pregnancies. Six cycles were proposed and the
      higher cumulative probability of pregnancy is obtained at the 4th cycle. The best
      pregnancy rate per cycle is obtained with 5.10(6) to 10.10(6) inseminated. The
      success rate is not associated with the number of sperm abnormalities in our
      study.

PMID- 9026277
TI  - [Prognostic sperm factors in intra-uterine insemination with partner's sperm].
AB  - We studied the prognostic value of sperm characteristics for the outcome of intra
      uterine insemination with partner sperm (IUIPS). A total of 712 cycles of IUIPS
      following induction of ovulation with gonadotrophin (hMG/hCG) for 277 sterile
      couples attending the assisted reproductive technology centre of Poissy Hospital
      (78300-France) between January 1991 and December 1994 was studied
      retrospectively. Ninety-two clinical pregnancies were obtained giving an overall
      rate of 12.9% per cycle. None of the characteristics of the sperm as assessed
      initially correlated with outcome. In contrast, the number of motile spermatozoa
      given (n) affected outcome: for n < 1 x 10(6) the pregnancy rate was 2%; for n =
      5 to 8 x 10(6) the rate was 19%. However, for +/- 8 x 10(6) the proportion of
      biochemical pregnancies and miscarriages was 40% which was significantly higher
      than for smaller concentration. The resort of IVF following 4 IUIPS failures
      leads to a pregnancy rate per cycle of only 6.7%.

PMID- 9026278
TI  - [Cervical dysplasia: is there a role for hysterectomy?].
AB  - Cervical intraepithelial neoplasia are usually treated by conservative
      procedures. Hysterectomy straightaway would have advantages but some drawbacks;
      reasons are listed.

PMID- 9026280
TI  - [Ovarian stimulation using a protocol of low dose agonist in patients with an
      elevated basal FSH].
AB  - This study compare the ovarian response of patients with high day 3 FSH (> 6.5
      UI/L), treated with two protocols; a protocol with a low dose of GnRH agonist and
      a so called "long protocol" with GnRH agonist in a depot formula. The ovarian
      response with the agonist low dose was better with less ampules (37.1 vs 46.6)
      and a shorter duration of stimulation (10.5 vs 12.4 days). The number of mature
      oocyte was higher (5.9 vs 4.5) as well as the number of good quality embryo (3.2
      versus 2.3). The E2 levels on day 8 was higher (1065 vs 460 pg/ml). The
      cancellation rate was lower (14% vs 26%). The use of the low dose protocol gave a
      better ovarian response for patients with high 3 FSH. Large randomized studies
      are needed to confirm these data.

PMID- 9026279
TI  - [Intrauterine copper contraceptive implants].
AB  - GyneFix, conceived in 1985, was developed to minimize three major problems
      frequently associated with discontinuation of IUD use: expulsion, bleeding and
      pain. Since the initial clinical investigations, over 10,000 women years of
      experience and up to 8 years of follow-up in international, multicenter, non
      comparative and comparative clinical trials, including a large proportion of
      nulligravid/nulliparous women, have been collected. The following conclusions
      were reached: 1. The unique design characteristics of GyneFix (frameless,
      flexible and fixed to the fundus of the uterus) have resulted in optimal
      tolerance and almost complete absence of expulsion. The result is enhanced
      effectiveness (comparable to OCs and male/female sterilization) and a high rate
      of continued use. GyneFix reduces the IUD-failure rate to a minimum and is,
      therefore, a welcome reversible alternative to OCs and female surgical
      contraception. 2. Frameless and flexibility explain the absence of side-effects
      and adverse events caused by dimensional incompatibility between the frame of
      conventional IUDs and the uterine cavity and may also explain the absence of PID
      and ectopic pregnancies in any of the clinical studies. 3. Insertion of GyneFix,
      with or without local anaesthesia, is easily accomplished in the office of a few
      minutes. Removal is easy, quick and painless. 4. GyneFix is an equally effective
      and well accepted method fro nulliparous women.

PMID- 9026281
TI  - [Pregnancy and systemic scleroderma. A case report].
AB  - The systemic scleroderma is an auto-immune affection characterised by diffuse
      lesions of the connective tissues with inflammatory predominance. As less
      frequent as this association with pregnancy, it usually occurs to the woman at
      the end of genital life activity. The obstetrical past history of a G5P2 of 40
      years old affected with systemic scleroderma, is marked by four tardive abortions
      and two premature deliveries. The evolution of the disease was progressively
      unfavourable with visceral, digestive and pulmonary blows them
      sclerodermatomyositis. A review of literature reveals the interactions between
      this affection and pregnancy. The aggravation of the disease during pregnancy is
      possible: nephopatic scleroderma is then the most frequent complication. The
      gynaecological and obstetrical consequences are sterility, habitual abortions,
      intra-uterine growth retardation, intra-uterine foetal death, premature delivery
      and expulsion difficulties. The infant prognostic is specially related to the
      risk prematurity. The corticotherapy is the only acceptable treatment during
      pregnancy.

PMID- 9026282
TI  - [Proceedings of the Scientific Conference on Radiation and Chromosomes. Dedicated
      to the memory of Professor N. V. Luchnik].

PMID- 9026283
TI  - [The "2 + 1" mechanism as the basis for synergism in the neutron-photon
      irradiation of the spermatozoal genome in Drosophila melanogaster].
AB  - Cytogenetic analysis of polytene chromosomes of Drosophila melanogaster locus
      specific mutants induced by consecutive neutron-photon irradiation has shown that
      their genome contains multiple intra- and inter-chromosome exchanges, including
      triradials, evidencing the synergistic action of such combined exposure. The
      appearance of the triradials may be only possible on the base of an interaction
      between a double and a single DNA strand breaks. The important significance of
      such interaction as the general mechanism for production of chromosome
      aberrations in irradiated cells of higher eucaryotes had been postulated by N. V.
      Luchnik as early as 10 years ago, but only nowadays it has been confirmed
      experimentally.

PMID- 9026284
TI  - [Chromosome aberrations, chromatin diminution and their significance in
      understanding the molecular genetic organization of eukaryotic chromosomes].
AB  - The paper analyzes the significance of new data obtained in the study of
      mechanism of formation of radiation-induced chromosome aberrations and in the
      investigation of chromatin diminution for understanding of the principles of the
      molecular genetical organization of eucaryotic chromosome. It is concluded that
      the structure of eucaryotic chromosome follows a certain plan. For its formation,
      a large number of various innovations were necessary, which could not been
      prepared simultaneously under the directed action of natural selection based upon
      the stochastic mutation process.

PMID- 9026285
TI  - [The radiation cytogenetics of multilocus deletions and the principles of the
      superchromomeric organization of eukaryotic euchromatin].
AB  - Fine cytological analysis of 72 gamma ray- and neutron-induced multilocus
      deletions (MLD) at the b, cn and vg regions of Drosophila melanogaster polytene
      chromosomes combined with the complementation assay at the b region is used to
      detect precisely the size and location of the MLD ends relatively to chromomeres
      and to each other. The basic principles of the MLD induction are found to be the
      same for three studied genome regions, showing that the folding of the interphase
      chromatin at the superchromomeric level is non-random and follows the
      megasolenoid-rosette model which is presented and discussed.

PMID- 9026286
TI  - [The use of dicentric distribution in human peripheral blood lymphocytes for the
      retrospective estimation of the irradiation dosage].
AB  - The paper presents the results of retrospective dose estimations in a number of
      Chernobyl victims by different approaches to the analysis of dicentric
      distribution in peripheral lymphocytes in blood samples taken a long time after
      the accident. Retrospective dose estimations are compared with dose estimates in
      the same individuals made immediately after the accident by dicentric
      frequencies.

PMID- 9026287
TI  - [An analysis of the cellular distribution of chromosome aberrations induced in
      human lymphocytes after a single irradiation and under conditions of preliminary
      adaptive exposure].
AB  - Irradiation by an adaptive dose 0.05 Gy at the G0 stage decreased the number of
      chromosome aberrations induced in lymphocytes by a challenge dose 0.5 Gy at the
      G2 stage. Adaptive response was not observed at the G1 stage, when the cells were
      exposed to adaptive dose 0.05 Gy and challenge dose 1.0 Gy respectively after 24
      h and 29 h incubation with PHA. In lymphocytes exposed to 1.0 Gy at the G1 stage,
      cellular distribution of chromosomal aberrations followed the Poisson
      distribution, while in lymphocytes exposed to 0.5 Gy at the G2 stage, the
      distribution of aberrations differed from the Poisson distribution and was nearer
      to the degenerated Poisson distribution. The adaptive dose 0.05 Gy did not alter
      the distribution of chromosome aberrations induced by the challenge dose at the
      G1 or the G2 stages. The role of independent and whole-cellular repair in the
      formation of chromosome and chromatid aberration is discussed.

PMID- 9026288
TI  - [Biophysical models of the formation of radiation-induced chromosome
      aberrations].
AB  - The brief analysis of the development of biophysical models describing the
      formation of chromosome aberrations is given. It is shown that, though the target
      theory is obsolete and does not correspond to modern radiobiological knowledge,
      however hit and target principles are still the basic radiobiological concepts.
      Three main directions of the development of biophysical models are submitted;
      their shortcomings and possible ways of perfection of the models are specified.

PMID- 9026289
TI  - [Spontaneous chromosome aberrations in cancer cells. The demonstration of the
      presence in them of hidden genetic structure damages].
AB  - Cultured HEp-2 cells (human larynx cancer cells) reveal significant variation in
      chromosome aberration rate. The study of its regularities at cell and population
      levels allowed to conclude that the cancer cells contain hidden lesions of
      genetic structures which, with certain probability, can reveal themselves as
      chromosome aberrations. Exposure of cancer cells to non-mutagenic agents
      (suboptimal temperature, low concentration of propilgallate or caffeine) resulted
      in the increase of frequency of cells containing chromosome aberrations above the
      control level, while the number of aberration per aberrant cell was not altered.
      Exposure of irradiated cells to the same agents induced, as in the case of
      spontaneous mutagenesis, the increase of the aberrant cell frequency, while the
      extent of their damage remained at the level characteristic of the effect of
      irradiation solely. The similarity of mechanisms for realisation of hidden
      chromosome lesions under the action of non-mutagenic agents in spontaneous and
      radiation-induced mutagenesis indicates the similarity of the nature of these
      lesions. The convincing evidence of existence of hidden genetic lesions in cancer
      cells was obtained in experiments with cloning of the initial population and
      analysis of chromosome aberrations in 22 clones. All the cells without any
      exception contained chromosome aberrations.

PMID- 9026290
TI  - [Stable and unstable chromosome aberrations in human blood lymphocytes in vitro
      after gamma irradiation].
AB  - Radiation-induced (137Cs-gamma-rays) aberrations in the first chromosome in human
      peripheral lymphocytes were investigated using FISH technique. It was shown that
      the most of detectable aberrations were translocations (about one half) often
      appearing with deletions: about 1/3 of the number of translocations were
      dicentrics; rings and insertions were rare.

PMID- 9026291
TI  - [The mutagenic action of gamma radiation on Chinese hamster cells. The
      cytogenetic characteristics of the mutants at the HPRT locus].
AB  - The peculiarities of mutation induction and cytogenetic characteristics of
      spontaneous and radiation-induced HPRT mutant clones have been studied. The
      linear-quadratic dependence of the mutation induction on radiation dose has been
      found. High heterogeneity of cytogenetic parameters (aneuploidy and chromosome
      aberration frequency) has been shown in the mutants.

PMID- 9026292
TI  - [The cytogenetic effects of low doses: the results of N. V. Luchnik and the
      current status of the problem].
AB  - The analysis of up-to-date state of the problem of quantitative assessment of
      cytogenetical effects in the range of low-level doses is presented. The
      importance of works of N. V. Luchnik is demonstrated for the development of this
      field of radiobiology. The results of the authors' own experimental and
      theoretical research on the regularities of induction of cytogenetical damage by
      low doses of ionising radiation are presented.

PMID- 9026293
TI  - [Changes induced by low doses of ionizing radiation in the accessibility to DNA
      restriction enzymes of the ribosomal gene system of human lymphocytes].
AB  - Human lymphocytes were X-irradiated at doses 0-10(-2) Gy and allowed to repair
      for some time. Nuclei were prepared and digested with restriction endonuclease
      Rsa I to selectively release 28S RNA gene fragment fraction, containing the DNA
      binding protein, Hpa II digestion of nuclei was used to investigate the
      methylation of the 28S RNA gene fragment. There was a differential enrichment of
      28S RNA gene binding protein for different X-ray doses with maximum enrichment
      for dose 2-3 x 10(-2) Gy with following diminish to 10 x 10(-2). The enrichment
      of less methylated fractions of 28S RNA gene was observed during X-irradiation.
      This might be explained by a different X-ray-induced changes of methylated and
      unmethylated rDNA binding with nuclear proteins. The possible mechanism for this
      phenomena are discussed.

PMID- 9026294
TI  - [A single mechanism for the initiation of different effects of low doses of
      ionizing radiation].
AB  - Main regularities of different endpoints of low dose effects (adaptive response,
      stimulation of proliferation, special radiosensitivity of lymphoid cells, and
      others) have been examined. It has been shown that these endpoints have a
      commonness for the dose interval, the shape of the dose-effect curve, the reverse
      effect of dose rate, non-specificity toward initiating agents, and others. An
      explanation is suggested for the common mechanism of the initiation of all the
      studied low dose effects, basing on the theory of the non-specific reaction of
      cell to external influences. It is concluded that initiation of the low dose
      effects is conditioned by radiation induced damage of functions of plasmic and
      internal membranes.

PMID- 9026295
TI  - [The chronic action of gamma radiation on a growing population of Saccharomyces
      cerevisiae yeasts at different dose rates].
AB  - Experimental data on the processes of division and death of haploid and diploid
      yeast Saccharomyces cerevisiae of wild type and of their radiosensitive mutants
      exposed under optimal for reproduction conditions to chronic action of gamma
      radiation at various dose rates are presented. It is shown that the dependence of
      the integral division/death process on time was exponential for all the studied
      strains. With dose rate increasing, the duration of the lag period and the
      probability of cell inactivation increased, while the multiplication rate
      decreased. These processes, for equal dose rates, were more expressed for the
      radiosensitive mutants.

PMID- 9026296
TI  - [The molecular, cellular and systemic mechanisms of the radioprotective action of
      multivitamin antioxidant complexes].
AB  - Exposure to radiation, as well as holding under conditions of limited mobility
      during 24 h induced decrease of thymus cell number in mice. Usage of water
      dispersed forms of beta-carotene with addition of vitamins E and C protected
      thymus against cellular devastation induced by irradiation and stress, and
      increased the efficiency of DNA repair in spleen of irradiated mice.

PMID- 9026297
TI  - [The effect of gamma irradiation on lymphocyte mechanical emission in rats at
      different stages of the cell cycle].
AB  - Mechanoemission (ME) of rat peripheral blood lymphocytes (PBL) over the radio
      frequency range has characteristic peculiarities in various stages of the cell
      cycle, both in unirradiated cells and in cells exposed to 0.25 or 1 Gy of gamma
      radiation. After 52 h incubation of irradiated and unirradiated lymphocytes, ME
      PBL indices take values equivalent to initial ones in the G0 phase. Increase of
      radiation dose from 0.25 to 1 Gy was followed by a decrease of the value of the
      ME PBL kinetic parameter after 24, 40 and maximum 48 h incubation.

PMID- 9026298
TI  - [Biometrical analysis in the radiobiology works of N. V. Luchnik].
AB  - The contribution of the famous Russian geneticist and biophysicist N. V. Luchnik
      into biometrical analysis of radiobiological data is discussed. His works on
      radiation mortality of mice and the process of post-radiation repair of
      chromosome aberrations are thoroughly observed. The conclusion of necessity to
      develop biometrical analysis as separate part of biometry is made.

PMID- 9026299
TI  - [The methodological aspects of experimental modelling and of assessing the
      hereditary sequelae of the irradiation of one and both parents].
AB  - The paper summarises some methodological approaches which may be used in
      experimental modelling and study of hereditary radiation effects in mammals.
      These approaches are aimed to the elucidation of the possible specific character
      (aggravation) of radiation damage in the offspring determined by the
      participation of two exposed parents in conception. The main attention is drawn
      to the dependence of hereditary radiation effects yield on the stages of the cell
      cycle of the parent germ cells at the moment of exposure and to criteria of
      evaluation of radiation damage in the offspring during the ontogenetic
      development.

PMID- 9026300
TI  - [The biological role of Vavilov-Cerenkov emission].

PMID- 9026301
TI  - [Pseudomutagenesis. The persistent increase in the level of cellular variability
      induced by radiation and some other agents].
AB  - Electron microscopic investigation of capillary endothelium cells in myocardium
      of irradiated rats revealed an unusual effect of persistent increase of
      probability of cell damage, similar in many relations to that described earlier
      for various unicellular species. New effect, unlike those traditionally studied,
      is characterised by non-stochastic nature, large number of the involved cells,
      reveals itself even after faint influences, and can be induced as well by agents
      other than radiation. The question is put on the probable commonness between
      these changes and the pseudomutagenesis which has the similar phenomenology.

PMID- 9026302
TI  - New high-performance liquid chromatographic method for amphotericin B analysis
      using an internal standard.
AB  - A simple and reproducible HPLC method for the analysis of amphotericin B (AmB) in
      serum, lung and liver using natamycin as the internal standard was developed. AmB
      and natamycin were extracted from serum, lung and liver and were separated using
      an isocratic elution from C18 reversed-phase column. The mobile phase consisted
      of acetonitrile-10 mM acetate buffer pH 4.0 (37:63, v/v). The HPLC system had two
      detectors in series. One was set at 303 nm and the other at 383 nm for the
      detection of natamycin and AmB, respectively. The retention times of AmB and
      natamycin were 15 and 6 min, respectively. The recovery efficiency was 96%-70%.
      The limit of quantification was 0.1 microgram/ml. The assay was reproducible, the
      within-day coefficient of variation (n = 6) was < 8% for serum, lungs and liver.
      The between-day variability (n = 6) was < 7.7% for serum, liver and lungs at 1
      microgram/ml or 1 microgram/g tissue concentration. The assay was linear within
      the range 1-40 micrograms/ml (r2 = 0.99).

PMID- 9026303
TI  - [Prevention of ocular infections in the hospital operating room].
AB  - Prevention of ocular nosocomial infections in the operation room requires control
      of several parameters: contamination of the air, a very important step of
      cleaning and sterilization and a staff trained to avoid infectious risk. The
      problem of PRION infection requires a particular attention especially about
      sterilization.

PMID- 9026304
TI  - [Traumatic and iatrogenic ocular infections: specimen handling and role of the
      laboratory].
AB  - Ocular inflammations may be due to a variety of diseases, and microorganisms play
      a major role in both acute and chronic eye diseases. Treatment of serious
      infections needs a good microbiological diagnostic. The indications and
      techniques for investigations are determined by the site of infection, severity
      of the process, and knowledge of the likely responsible organisms. Immediate
      inoculation of specimens on culture media in the examining room is often
      recommended. This article describes organisms associated with ocular infections,
      and is designed to assists ophthalmologists in the collection, processing and
      transport of specimens.

PMID- 9026305
TI  - [Infectious complications of corneal surgery].
AB  - The frequency of infectious complications after corneal surgery depend on the
      type of surgery: after trauma and perforations, corneal graft and perforations,
      and thus the previous status of the eye, surgical care and patient follow-up.

PMID- 9026306
TI  - [Emergency corneal grafts].
AB  - Corneal ulceration leading to perforation can mainly occur after infection,
      trauma, corneal dryness and exposure keratitis. When corneal ulceration does not
      respond to medical treatment, a penetrating keratoplasty allows the elimination
      of infected tissue and antigenic material. It can restore the integrity of the
      anterior segment of the eye. The tissue taken could serve for bacteriologic
      research. In spite of the great number of complications the percentage of success
      is about 50%.

PMID- 9026307
TI  - [Infectious corneal complications of contact lenses].
AB  - Keratitis in general may be caused by a large variety of microorganisms. The wear
      of contact lenses, mainly of soft material, increases the risk of corneal
      infection particularly by pseudomonas and acanthamoeba. The clinical aspects, the
      diagnostic procedures and the treatments are considered. With any type of lenses,
      rules of hygiene must be observed avoiding a brief tapwater rinse in order to
      decrease the risk of infection.

PMID- 9026308
TI  - [Microbiological and serological verification of cornea donors].
AB  - A study was made during 1994 about microbiological contamination on the donor
      eyes before enucleation of whole globe. We studied the efficiency of the
      decontamination method by checking sterility of corneal storage medium after two
      days. We give results of serological tests on 252 donors.

PMID- 9026309
TI  - [Infectious complications of cataract-implant surgery].
AB  - We hold a review of essential notions concerning frequency, origin and signs of
      the infection that can follow an extra capsular cataract extraction with
      insertion of an intraocular lens. Prevention is briefly considered.

PMID- 9026310
TI  - [Surgery for glaucoma and endophthalmitis].
AB  - The incidence of endophthalmitis after glaucoma surgery appears to be related to
      surgical procedures. After trabeculectomy the incidence is low from 0.06% to 0.2%
      but trabeculectomy with adjunctive antimetabolites increases the risk to 3% or
      more. Early onset endophthalmitis is due to the penetration of germs from
      patient's own external flora during the surgery, especially staphylococcus
      epidermidis.

PMID- 9026311
TI  - [Perforating injuries: management of the repair of scleral and corneal injuries].
AB  - The perforating injuries of corneal and scleral with and without foreign body
      must be localised and treated in urgency. The rule of repairing and prophylaxis
      of complications must be carefully respected.

PMID- 9026312
TI  - [Prevention of infections in the ophthalmology office].
AB  - Transmission of infectious agents from a patient to the following one in the
      medical office may result from infected collyria, from contact to the cornea by
      infected instruments or simply by the hands of the medical staff if some rules of
      hygiene are not respected. The prevention comprises the instillation without
      contact of the collyria, the adequate disinfection of instruments and the
      frequent hand washing. The disinfection of the tonometers and contact glasses
      aims particularly the elimination of viruses. If the virus of herpes, hepatitis
      and acquired immunodeficiency are eliminated by hypochlorite, oxygenated water
      and alcohol after 10 minutes, the adenovirus which is not coated is on the other
      hand resistant to alcohol and may survive several days on instruments. Ideally
      the disinfection would have to be performed between each utilization by soaking
      in bleach water at 500 ppm, or in chloramine 0.5%, or in hydrogen peroxide 3%
      (during 10 minutes). The alcohol may damage the glue of diagnostic contact lens.
      The hypochlorite attacks the metal. In case of possible contact with the blood of
      the patient, the wear of gloves is counseled (for example for fluorescein
      angiography) and is of course mandatory for surgical procedures in the office
      like excision of chalazion or keratotomy. Disposable needles will be thrown in
      solid wall containers reserved to this aim without being recapped.

PMID- 9026313
TI  - [Role of vitrectomy and intra-vitreous injections in the treatment of traumtic
      and iatrogenic endophthalmitis].
AB  - The survey of recent literature emphasises the usefulness of primary vitrectomy
      in the treatment of the most serious endophthalmitis. As soon as vitreous and
      aqueous humor samples have been obtained for bacteriologic analysis, intravitreal
      injection of a combination of antibiotics able to cover the most common causative
      germs is established as the standard of care. The beneficial effect of
      intravitreally-injected corticosteroids is still controversial.

PMID- 9026314
TI  - Otlx2, an Otx-related homeobox gene expressed in the pituitary gland and in a
      restricted pattern in the forebrain.
AB  - The vertebrate nervous system forms by the specification of, successively,
      neuroepithelial regions and cell groups. One of the proposed major histogenic
      steps is the subdivision of the neural tube in compartments along its
      caudorostral and dorsoventral axis. This event is reflected, and may be directed,
      by the restricted expression of many transcription factors. Here, we report on
      the isolation of a new homeobox gene of the paired superclass, Otlx2, whose early
      expression pattern in the mesencephalon and prosencephalon is congruent with
      proposed neuromeric models of brain morphogenesis. In addition, its late
      embryonic and postnatal expression, in clear continuity with the earlier pattern,
      suggests a role in the neuronal differentiation and the histogenesis of several
      prosencephalic and mesencephalic areas. Finally, Otlx2 is expressed from the
      earliest morphogenetic events in the Rathke's pouch, the anlage of the
      adenohypophysis, an expression site shared by a very close homologue,
      Otlx1/Ptx1/P-Otx.

PMID- 9026315
TI  - The role of an agrin-growth factor interaction in ACh receptor clustering.
AB  - The clustering of acetylcholine receptors (AChRs) at the neuromuscular junction
      is mediated in part by the heparan-sulfate proteoglycan agrin. However, our
      previous studies have also suggested the role of heparin-binding growth
      associated molecular (HB-GAM) in AChR clustering. Here the role of an agrin-HB
      GAM interaction in this process was examined using cultured Xenopus muscle cells.
      Agrin-coated beads further treated with HB-GAM were highly effective in AChR
      cluster induction. Protein overlay assays showed specific binding of HB-GAM to
      agrin. In addition, agrin-enriched neuritic tracks bound HB-GAM in a manner that
      showed a high degree of colocalization between the neural agrin and the applied
      factor. Finally, the introduction of exogenous HB-GAM together with soluble agrin
      resulted in the appearance of AChR clusters on the dorsal surface of cells in an
      agrin isoform-dependent manner; a dramatic change from the characteristic ventral
      AChR clustering seen in response to agrin alone. These results suggest that agrin
      may mediate AChR clustering by interacting with muscle-bound heparin-binding
      growth factors such as HB-GAM.

PMID- 9026316
TI  - Postsynaptic element contributes to the delay in synaptogenesis in synapsin I
      deficient neurons.
AB  - In a previous study, we reported a retardation in process outgrowth and synapse
      formation in cultured hippocampal neurons from synapsin I-deficient mice. Here we
      investigated whether this delay in synaptogenesis was attributable to pre- or
      postsynaptic elements. The experimental paradigm used in this study involved the
      establishment of heterochronic cocultures of neurons from wild-type and synapsin
      I-deficient neurons established synapses with mature wild-type postsynaptic
      elements after 24 and 72 h, respectively. In contrast, synapsin I-deficient
      postsynaptic elements were able to receive synapses only after 9 days in culture,
      representing a 5-day delay compared to controls. The results suggest a broad role
      of synapsin I in the structural development of the synapse, participating
      directly or indirectly in the maturation of both presynaptic and postsynaptic
      sites.

PMID- 9026317
TI  - [Immuno-nutritional recovery of children with severe malnutrition].
AB  - In developing countries, more than 12 million children die each year from the
      combined effects of malnutrition and infection. Malnourished children have
      impaired cellular immunity and are particularly sensitive to opportunistic
      infections. However, immune recovery has rarely been investigated during
      nutritional rehabilitation. Indeed, mortality remains high during renutrition,
      and relapses are frequent. We established a center in Cochabamba, Bolivia,
      specifically to save these children by treating both clinical and nutritional
      problems and restoring immune function. The CRIN (center for immuno-nutritional
      recovery) admits children with severe malnutrition from the Cochabamba suburban
      area. They are from low income families, in crowded living conditions with poor
      sanitation and are weaned early. Nutritional diagnosis was based on weight-for
      height, arm to head circumference ratio and clinical examination for edema, loss
      of subcutaneous tissue and diminished muscle mass. The children were examined
      daily, and first treated for respiratory and intestinal infections. Sociological
      and psychological aspects were also included in our holistic approach to treating
      severe malnutrition. Children received a four-stage diet lasting 2 months. During
      the initial phase (1 week) they were given an oil-sugar-milk based diet, with
      half lactose concentration, seven times a day. This supplied 1.5 to 2.5 g of
      protein and 120 to 150 kcal/kg of body weight, according to the PEM pattern.
      Protein and energy intake was then slowly increased during the transition phase
      (1 week). During the next, 'calorific-protein bombing' phase (6 weeks) 5 g of
      protein and 200 kcal/kg of body weight were given daily, such that there was
      sufficient energy for protein accumulation. During the last, discharge phase (1
      week), the protein and energy contents were slowly decreased. Weight, height, arm
      and head circumferences, and triceps skin-fold thickness were measured weekly by
      standardized methods. Thymus size was assessed weekly by mediastinal ultrasound
      scanning with a portable scanner (ALOKA SSD-210 DXII, Tokyo) using a 5 MHz linear
      pediatric probe. Lymphocyte subpopulations in peripheral blood were investigated
      monthly using monoclonal antibodies. Compared to controls, the malnourished group
      had severe involution of the thymus, a significantly higher proportion of
      circulating immature T lymphocytes and a lower proportion of mature T
      lymphocytes. The two month longitudinal study showed that normal anthropometric
      values (90% NCHS weight for height) were recovered after one month of
      rehabilitation. However, immune recovery (thymic area of 350 nm2) required two
      months. This may explain the frequent relapses among malnourished children
      discharged after one month on the basis of 'apparent nutritional health'. Such
      children may remain immunodepressed, and should therefore be considered as high
      risk children. To test an immunostimulatory treatment, we designed a historical
      cohort study of malnourished children who received 2 mg of zinc per day. The
      children were matched for age, sex, anthropometric criteria and nutritional
      status with malnourished control children (treated previously with zinc).
      Anthropometric recovery was obtained in both groups in one month. Children
      receiving zinc attained immunological recovery within one month, whereas children
      not receiving zinc took two months. Thus zinc hastened immunological recovery
      concomitant with nutritional recovery such that the duration of hospitalization
      could be halved: after one month of this immuno-nutritional treatment,
      malnourished children appear to be sufficiently healthy to face their pathogenic
      home environment.

PMID- 9026319
TI  - [Ambulatory management of moderately and severely malnourished children in the
      rural health district of Kapolowe in Shaba (Zaire)].
AB  - In Kapalowe rural health district, hospitalisation of malnourished children is
      restricted to complicated cases; once the complication is under control or
      eliminated, the child's treatment is continued at home, based on a 13 weeks
      contract, between parents and health centre. The parents commit themselves to
      feed their child four times a day (two porridge and two family dish portions), to
      consult once a week at the health centre and to welcome a weekly home visit. The
      objective of this visit is to support the parents, to detect possible problems
      and to reach the roots for this particular child. During the contract period,
      cost of medical treatment and recommended soya flour, is borne by the parents
      through a lump sum contribution. In this article, data concerning the first 95
      children home rehabilitated (1989-1991) in Kapalowe are analysed. Characteristics
      of these children are classical regarding malnutrition; for example, age
      distribution is similar to that of weaning and of defunction of children at the
      hospital during the same year. Approximately half of them are still breastfed at
      the beginning of the contract. Most of them are correctly immunized and have been
      seen at the health centre at least two times in the last six months. Seventy-four
      children finished the contract; there were 17 abandons and 4 deaths. Weight gain
      is inferior to that observed in specialized feeding centres which do benefit from
      external resources, which is not the case here. It was not possible to show a
      significant catch up for the height for age indicator after the three months
      contract. These anthropometrical results are less important than the global and
      subjective improvement in the child's general health status observed at the end
      of the contract. None of the children reached the target weight after 13 weeks
      but important changes were observed in their behaviour, in their resistance to
      infection and in the attitude of their parents. The parents generally followed
      the instructions quite well. The middle of the contract seems to be a key period
      when either significative changes happen or when the attention is released.
      Treatment instructions have been amended to avoid monotony and overload, and to
      stimulate staff creativity and self-satisfaction. Payment was not a problem for
      the parents as malnutrition is not linked to extreme poverty. Mother's attitude
      and confidence and child initial weight for height status are two important
      contract success determinants. Abandons are more frequent when the mother is
      pessimistic and in case of kwashiorkor. Despite this, most of these children had
      gained more than one kilo before the contract was interrupted. Some didn't
      fulfill the W/H inclusion criteria (-2 standard deviations) and should probably
      not have been under contract. The four deaths were linked to insufficient
      treatment instructions for usually banal diseases that have another meaning in
      case of malnutrition, such as diarrhoea, fever, etc. An evaluation performed
      three months after the end of the contract in 26 children show 13 further
      improvements, 8 statu quo, 4 relapses and 2 new deaths. Conclusions are that home
      nutritional rehabilitation is possible where a health district is fully
      operational, that anthropometric data are useful to monitor rehabilitation but
      not to be pursued only as sole and ultimate objectives, and that adequate follow
      up after the first intensive stage is essential. The paper also shows how such a
      research result can have direct consequences on the organization of health
      activities.

PMID- 9026318
TI  - [Vitamin e supplementation in Senegalese children with kwashiorkor].
AB  - Kwashiorkor continues to be a major cause of infant mortality in the developing
      world. It has recently been suggesting that this form of malnutrition is due to
      oxidizing aggression. Vitamin E is a powerful natural anti-oxidant, and we
      therefore investigated the extent to which its supplementation in the diet
      contributed to treating child kwashiorkor. Vitamin E was also administered to
      children suffering from marasmus. The study was conducted from October 1993 to
      July 1994 and included 79 children (38 cases of kwashiorkor and 41 of marasmus).
      The treatment resulted in a 76% success rate, with the best results for marasmus
      (89.5% cure). However, the supplement did not have any effect on the nutritional
      status for either the kwashiorkor or marasmus patients. In the kwashiorkor group,
      the weight increase, after disappearance of edema was 15.2 +/- 4.9 g/kg/d in the
      supplemented group as compared to 16.4 +/- 3.6 g/kg/d in the control group. The
      duration of edema along treatment was similar for the two groups (supplemented:
      8.6 +/- 3.1 days, control group: 7.1 +/- 3.9 days). Possible reasons for vitamin
      E supplementation having no effect are discussed.

PMID- 9026320
TI  - [Should ambulatory nutritional recovery centers in Niamey (Niger) be closed?
      Analysis of the situation, proposals and evaluation of an intervention].
AB  - In Niger, malnutrition underlies the high child mortality (319/1,000). The
      prevalence of acute malnutrition (weight/height below minus 2 z score) is more
      than 16% in the 0 to 5 year old range. The situation in the urban areas in
      slightly better than average (child mortality of 210.3/1,000). Thus the situation
      is very serious. The efficacy of intensive nutritional rehabilitation centers and
      ambulatory nutritional rehabilitation centers is controversial. The practices and
      knowledge of the staff of the ambulatory centers in Niamey was studied by weekly
      session meetings. The shortcomings could be explained by the absence of
      individual care, the additional work for the mothers, the mothers' illiteracy,
      the costs, the domestic problems and problems of cultural support, passivity of
      screening for malnutrition associated with the very low and irregular nutritional
      value of the meals supplied to the children. However, these centers exist, and
      they have staffs. The sessions were therefore used to develop and implement
      alternative strategies, and the role of the ambulatory units was discussed. The
      program was evaluated according to mothers' compliance, children's nutritional
      status, length of stay, rate of transfer to the hospital scored by retrospective
      analysis of the data for 397 children followed between July and October for each
      1993, 1994 and 1995. The nutritional status on admission was similar for each of
      the three years (weight/height - 2.6 z score). The number of children with weight
      gain increased from 35 to 127 (P < 0.005). The rate of loss to follow-up
      decreased from 67% to 32% (P < 0.005). In 1993 the mothers were expected to
      attend daily. In 1995, after 5 to 10 days of training, follow-up was once weekly.
      The length of care decreased from 64.3 to 46.9 days for a similar weight gain
      (3.5 g/kg/day). Transfer to the hospital decreased from 10.7% in 1993 to 5.7% in
      1995 (P < 0.0001), whereas this score remained high in the Niamey health centers
      without and ambulatory unit (24.7 in 1995). Thus the efficacy of these units can
      be improved although long-term outcome has yet to be demonstrated. It is also
      necessary to improve screening of malnourished children attending daily out
      patients clinics.

PMID- 9026321
TI  - [How can food supplementation to young children be improved?].
AB  - The various forms of malnutrition start to appear around the age of six months,
      once the mother's milk is insufficient for all the needs of the child. There are
      various factors which contribute to dietary insufficiency during weaning, but the
      most important is that foods used to supplement milk do not have a high enough
      energy density. Gruels prepared from cereals and root crops are given to many
      children. They have a very high starch content, and must therefore be extensively
      diluted for the viscosity to be acceptable to the child. There are various
      methods available to reduce the swelling capacity of starch. The aim is to
      increase the dry matter content (and thus energy content) of gruels, without
      increasing their viscosity. Hydrolysis of starch by amylases of various origins
      is possible. Current knowledge about starch hydrolytic activities and nutritional
      consequences suggest that it may be valuable to use germinated cereals
      domestically and for small-scale production, and use industrial amylase for
      larger scale production. In urban environments, these technologies should be
      encouraged among street food vendors and small food businesses.

PMID- 9026322
TI  - [The effect of energy density and viscosity of porridges on the energy intake of
      infants].
AB  - It has been known for at least 25 years that high energy density and low
      viscosity are desirable attributes of complementary foods. However, the effects
      of increasing energy density and reducing viscosity of gruels on infant energy
      intake have only been studied in the last 10 years. Works published between 1986
      and 1992 were carried out with infants randomly selected in urban slums or rural
      areas in India and Tanzania. When gruels are given in a single meal, all of them
      showed higher energy intake with both high energy-dense and low viscosity gruels.
      But these studies do not give information about the effects of these gruels on
      daily energy intake from gruels and on total daily energy intake when they are
      given with feeding frequencies corresponding to traditional weaning practices.
      Works published since 1992 were conducted among infants suffering from or
      recovering from acute diarrhoea or severe malnutrition. A positive effect of
      increasing energy density of gruels was observed not only on energy intake from
      gruels but also on total energy intake. On the other hand, effectiveness of
      reducing viscosity was not clearly demonstrated. Further studies are required,
      particularly to identify the conditions for which high energy dense gruels
      prepared from bulk-reduced starchy staples are able to significantly improve
      infant energy intake.

PMID- 9026323
TI  - [Subcutaneous and soft tissue involvement associated with AIDS: ultrasonographic
      aspects. Apropos of 3 cases].
AB  - Subcutaneous and soft tissue involvement is frequent in AIDS patients. Although
      the relevant clinical characteristics have been extensively described in the
      literature, there has been little work on the radiological features. We therefore
      report three cases of AIDS with subcutaneous and soft tissue involvement: two
      cases of pyomyositis and one case of non-Hodgkin's lymphoma. All three were black
      African men and were aged 22, 28 and 41 years. They were diagnosed as suffering
      from AIDS and were HIV1 and HIV2 positive. Diagnosis was established using needle
      puncture and histological (lymphoma) and bacteriological (pyomyositis)
      examination. We report ultrasound scan findings. The features of the pyomyositis
      differed from those usually observed in immunocompetent patients. The lymphoma
      nodules were similar to those described in the literature. They were hypoechoic
      and homogeneous, with no necrotic center. We believe that subcutaneous and soft
      tissue infectious involvement, for example pyomyositis, is more frequent in
      tropical regions than tumors (Kaposi's sarcoma, lymphoma) which are more frequent
      in Europe. This soft tissue involvement can be considered to be part of the
      particular picture which is "tropical AIDS".

PMID- 9026324
TI  - [Recent results on the pharmacodynamics of Strychnos malgaches alkaloids].
AB  - Investigation of Strychnos (Loganiaceae) shrubs and trees was initiated by their
      traditional uses of their inherent poisons on arrows: this led to the discovery
      of strychnine and curare alkaloids. Subsequently, phytochemical investigation of
      several Strychnos species has shown great structural diversity of the alkaloid
      constituent which also display various biological effects, i.e. convulsive and
      relaxant effects on muscles, and antimicrobial, antitumor and antihypertensive
      properties. Ethnobotanical field work conducted in different regions of
      Madagascar revealed that infusion of three Strychnos species, S. mostueoides, S.
      myrtoides and S. diplotricha, is used in association with subcurative doses of
      chloroquine to treat chronic malaria. Bioassayfractionation led to the isolation
      of two major bioactive components, strychnobrasiline and malagashanine. Whereas
      strychnobrasiline is a previously known chemical compound, malagashanine is the
      first in a series of a new subtype of Strychnos alkaloids. These two alkaloids
      are devoid of intrinsic antimalarial effects, both in vitro (IC50 = 73.0
      micrograms/ml for strychnobrasiline and 69.1 micrograms/ml for malagashanine) and
      in vivo (10 mg/kg conferred a 5% suppression of parasitemia). When these
      alkaloids are combined with chloroquine at doses much lower than required for
      antiplasmodial effects, they greatly enhance the chloroquine action in a dose
      dependent manner as seen by the isobologram method. Several minor alkaloids
      structurally related to malagashanine were also isolated from Madagascan
      Strychnos. They all enhance, to greater or lesser degrees, the chloroquine
      effectiveness. Interestingly, there is a positive correlation between the
      ethnomedical use of the three Strychnos species as chloroquine adjuvants and the
      chloroquine-potentiating effects of malagashanine and strychnobrasiline isolated
      from them. After preliminary toxicological studies, infusion of stem barks of S.
      myrtoides in association with chloroquine was successfully evaluated in a
      clinical setting. Additional chemical, pharmacological and toxicological work is
      being conducted on these alkaloids with the aim of developing purified and
      standardized extracts for clinical trials. These trials will be carried out in
      the chloroquine-resistant regions of Madagascar which are in need of inexpensive
      and efficient drugs for the treatment of chloroquine-resistant malaria.

PMID- 9026325
TI  - [Extramembranous glomerulonephritis and cysticercosis].
AB  - We report a case of impure nephrotic syndrome occurring during cysticercosis.
      Renal biopsy showed membranous glomerulonephritis, indicating that there were
      immune complexes involved in reaction to this parasite. The patient had
      previously received prednisolone treatment without any success. Subsequently,
      treatment with praziquantel was followed by the disappearance of subcutaneous
      nodules with a decrease of proteinuria. This led to a remission of the nephrotic
      syndrome and, after an immediate post-therapeutic peak, lower serologic levels.
      Also, after an immediate post-therapeutic peak, creatinemia reached the proper
      value, which was lower than before the treatment, within twenty months of
      evolution. Because nephropathy complicated the cysticercosis and the
      antiparasitic treatment was favorable, research on this type of infection is
      interesting. Also, the serology of cysticercosis should be added to the list of
      antigen tests which could identify the cause of membranous glomerulonephritis.

PMID- 9026327
TI  - [The use of diagnostic and therapeutic algorithms in the management of of
      sexually transmitted diseases in developing countries].

PMID- 9026326
TI  - [An ascaris in the lacrimal duct. Apropos of a case in Zaire].
AB  - A male adult Ascaris lumbricoides worm has been extracted from lacrimal canal of
      a 9 months old child living in Zaire.

PMID- 9026328
TI  - [The Francqui Prize 1996 awarded to Etienne Pays].

PMID- 9026329
TI  - Lipid messengers in the nervous system. Proceedings of a satellite symposium of
      the 15th meeting of the International Society for Neurochemistry. Tokyo, Japan,
      June 28-30, 1995.

PMID- 9026330
TI  - Successful use of size-mismatched liver allografts in children by delayed primary
      closure of the abdominal wall.
AB  - Children who are too ill to await a liver graft of suitable size may be
      transplanted with a relatively oversized graft by leaving the abdominal wound
      partially open, the defect reduced being bridged with polypropylene mesh and the
      mesh reduced in stages until it can be removed and the wound directly closed.
      This technique has been used in seven children who received nine grafts (five
      reduced and four full size). Their mean age was 7.3 (range 0.5-11) months and
      mean weight 5.8 (range 2.3-7.2) kg. Progressive reduction in the size of the
      transplanted liver made primary closure possible in survivors in up to four
      stages. Over a follow-up period of 3 to 58 months, five of the nine grafts and
      five of the seven patients survived. No significant complications attributable to
      the technique were encountered. The technique of delayed primary abdominal wall
      closure may be of benefit in children at risk of graft failure because of a size
      mismatched graft.

PMID- 9026331
TI  - Alterations in intestinal function in acute pancreatitis in an experimental
      model.
AB  - Gastrointestinal tract failure may be involved in the development of systemic
      septic complications in acute pancreatitis. Systemic and intestinal circulation,
      intestinal permeability and absorptive function were evaluated in the early
      course of acute pancreatitis induced in rats by retrograde intraductal injection
      of 0.2 ml of 5 per cent sodium taurodeoxycholate and 0.4 nmol trypsin. A decrease
      in systemic arterial pressure and intestinal blood flow and an increase in
      intestinal permeability as measured by the leakage of 125I-labelled human serum
      albumin from blood to lumen were noted in the distal ileum and colon, reaching
      statistically significant differences 6 h after induction of pancreatitis. The
      transport of small molecular markers (sodium fluorescein and 51Cr-labelled
      ethylenediamine tetra-acetic acid) through the distal ileum and colon in vitro
      from the mucosal to the serosal site in Ussing chambers significantly increased
      in the early periodic (20-60 min) of incubation, while the passage of a
      macromolecular marker (ovalbumin) demonstrated a definite increase at 60-120 min
      of incubation. D-Xylose absorption from the gut lumen to the portal vein was
      significantly less in acute pancreatitis than after sham operation. Intravenous
      administration of the hydroxyl radical scavenger dimethylsulphoxide prevented the
      compromised intestinal permeability and gut absorptive capacity induced by acute
      pancreatitis, but did not affect the reduced arterial pressure and intestinal
      microcirculation. Cytotoxic oxygen-derived free radicals may contribute to the
      development of alterations in intestinal permeability and absorptive function
      found in the early stage of acute pancreatitis in the rat.

PMID- 9026332
TI  - Laparoscopic cholecystectomy in a patient receiving continuous ambulatory
      peritoneal dialysis.

PMID- 9026333
TI  - Audit of general practitioner referrals to a surgical assessment unit: new
      methods to improve the efficacy of the acute surgical service.
AB  - A total of 653 referrals from general practitioners to an acute surgical service
      were audited prospectively over a period of 4 months. Middle-grade staff
      accepting these referrals were able to deal with 182 (27.9 per cent) of these
      cells without surgical admission. A further 189 (28.9 per cent) referrals were
      seen on a surgical assessment unit and were not admitted to a surgical ward. The
      resultant cost saving was approximately 10,000 pounds. This confirms that the
      ready provision of an experienced surgical opinion in combination with early
      assessment can reduce the number of unnecessary acute surgical admissions
      referred from general practitioners.

PMID- 9026334
TI  - Mediawatch. Mad minister disease?

PMID- 9026335
TI  - [Perspectives on work capacity of the elderly].

PMID- 9026336
TI  - [Overcoming age barriers in occupational life--problem field regarding
      qualifications].
AB  - First, an overview of current employment trends and training problems of older
      workers is given. Initiatives by selected companies and employment organizations
      then give an indication of the range of"good practice" which already exists to
      train older workers at work. An individual case study provides a more detailed
      insight into why such schemes are developed and which approaches are adopted.
      Finally, conclusions are drawn from both the organizational descriptions and
      empirical research and recommendations on how to improve the training situation
      of older workers are given.

PMID- 9026338
TI  - [Elderly working women--late stages of employment and transition to retirement].
AB  - The employment of elderly women has become increasingly important. Changes in
      employment patterns have led to an increase in the number of working middle-aged
      women, especially among women with children and families. The later employment
      years of middle-aged women are characterized by problems at work and in the
      labour market which are caused by insufficient skills and poor health. The
      transition to (early) retirement does not follow any specific patterns. It is
      shaped by health and financial conditions and family concerns. A large percentage
      of retired women have difficulties adjusting to retirement conditions. An
      analysis of this status passage must include all scopes of action of elderly
      employed women.

PMID- 9026337
TI  - [Performance capacity of elderly workers--internal and external influencing
      factors].
AB  - Internal and external factors affecting ability and performance of older
      employees are being analyzed in a short literature review. Internal factors like
      physical capacity, sensory capacity, cognitive abilities and general health are
      reduced with ageing; their effect on performance, however, depends upon the
      specific constellation of abilities needed in work tasks and roles. Accumulating
      experience and work motivation compensate for decreases in most cases or even
      enable better performance than in younger age groups. High labour costs and
      negative age stereotypes continue to dismissals, refusal of training and
      discrimination in the labour market.

PMID- 9026339
TI  - [Consensual and conflictual early retirement--flexible transition to retirement
      within the context of different labor force strategies].
AB  - 20 case studies were carried out in different firms in East and West Germany to
      analyze the process of decision-making in early retirement. The results show the
      embeddedness of decision making into the respective labour force strategies of
      the firms. In companies with "internal labour force strategies" there is a
      consensus-oriented process of decision-making based on negotiations of the
      participants. In companies that mainly employ skilled workers, however, the
      process of decision-making is rather conflict-oriented. So, there is evidence
      that companies' policies on early retirement are two-edged. The consequences of
      these findings are discussed.

PMID- 9026340
TI  - ["Retirement at age 58"--improvement or deterioration of living status?].
AB  - The BRD social security system contains numerous regulations concerning the
      smoothness of regulating social security benefits between unemployment benefit to
      pension benefit. Raising the retirement age for unemployed will lead to long-term
      unemployment or to a decreasing pension payment in the case of early retirement.
      In both cases the material income situation will deteriorate. Using the
      regulation for people who are or will be unemployed at the age 58, it can be
      shown that benefits were already clearly reduced before the new regulation of
      14.2. 1996 come into effect-especially for those with unemployment assistance.
      The political objective of reducing the extent of early retirement will be paid
      by the unemployed themselves.

PMID- 9026341
TI  - [Partial pensions: futuristic social policy innovation or only an alibi?].
AB  - The 1992 Pension Reform Act makes it possible that all old age pensions in
      Germany can be claimed as partial pensions with the objective of extending
      working life and creating the opportunity of a phased exit from the labour force.
      Disappointingly little use was made of this new form of flexible retirement. One
      main reason seems to be the unfavourable labour market situation in Germany,
      favouring an early exit from the labour force. This article investigates to what
      extent the design of the partial pension is responsible for its failure and how
      it could be modified in order to create, in accordance with the new "Part Time
      Work in Old Age Act", a system of gradual retirement which helps to stabilise the
      financial base of the pension system.

PMID- 9026342
TI  - [Part time work instead of early retirement: successful breakthrough for flexible
      and later retirement?].
AB  - In order to stop the trend towards early retirement in Germany a law to promote
      partial retirement recently has been passed by parliament. Concerning the impact
      on the labour market the raising of the pension age for older unemployed which is
      fixed in this law has to be seen as contraproductive and it will deteriorate the
      financial situation of unemployed older workers. Concerning the implementation of
      partial-retirement as such, there are momentous obstacles to realize part-time
      working arrangements in practice: the insufficient financial compensation for
      older workers and the obligation for employers to hire unemployed workers.
      Supplementary collective agreements are seen to be necessary to establish part
      time work for older workers.

PMID- 9026344
TI  - [Change in daily activities in the transition to retirement in single persons and
      couples].
AB  - Basic changes of daily activities during the period of transition to retirement
      according to the concept of the household approach are described with the help of
      results of empirical research. From the point of view of the household approach
      the transition to the phase of post-professional life is a sophisticated movement
      which is integrated in households, affects cycles of individual biographies and
      families just as individual and social structures in general and is linked with
      one or more changes of position and status from the dual pattern of job and
      freetime to the monistic private time schedule at the disposition of each
      household. The interpretations of the singles and couples questioned about their
      views of the period of transition to retirement are taken into account.

PMID- 9026345
TI  - [Retirement activities: wish or reality?].
AB  - The discrepancy between the potential and the reality of productive aging is very
      substantial. We have to deal with a structural gap. The individual productivity
      of aging is much more developed than the options of society for productive aging.
      Two ways of overcome the structural discrepancy are discussed. First options for
      post-retiremental activities are described. They follow the aim to enrich the
      role activities of elderly people by job options and honorary work. Second the
      model "Aktion 55" is discussed as an innovative initiative for new post
      retirement activities. Future interventions have to follow demographic changes by
      developing age-integrated social roles and to leave age-differentiated activities
      and roles.

PMID- 9026343
TI  - [From early retirement to retirement--change and stability of the social status
      of East Germany early retirees].
AB  - This article deals with the social effects of early retirement in East Germany.
      On the basis of a panel survey with two waves (1993 and 1996) it is shown that
      the social effects of early retirement have to be considered on a differentiated
      level and with regard to the time when the survey was carried out. After a
      difficult phase of transition the social situation of the people gradually starts
      to stabilize. Despite the experience of loss the judgements are ambiguous and
      often unstable. The results of the second wave mainly show an improvement of the
      social situation and a change in the set of criteria. Moreover, people recognize
      deficits in their social relations and tend to activate contacts outside their
      families.

PMID- 9026346
TI  - [Change in East Germany intergenerational relations in a large city. Results of
      the 4th survey phase of the Halle Longitudinal Study of participants of the 1994
      senior college (HALSEKO)].
AB  - The fourth survey by standardized questionnaire in November 1994 (response rate:
      71.6%, n = 308, mean age: 68.1 years) to identify effects of the changes in the
      eastern German cultural and social scene among senior students enrolled at the
      Martin Luther University Halle-Wittenberg since 1989 (HALSEKO) revealed a
      distinct deterioration in intergenerational relations which has been interpreted
      in terms of Mead's theoretical conception of the induction of intergenerational
      conflict by the abrupt change in cultural values in the new Federal states.
      Negative assessment were given by 69.5% (1992: 33.4%). Statistical analysis by
      bivariant contingency tables yielded an assessment pattern with two dimensions.
      These consisted personal discrimination by younger people and changes in
      intrafamilial intergenerational relations owing to fewer contacts, stress due to
      the job situation for children and grandchildren, tension within the family and
      anxiety at the thought of loneliness. The latter causes have a hurtfull effect.
      The list of possible causes for the deterioration in intergenerational relations
      that formed part of the questionnaire showed that most subjects considered
      unemployment (71.3%) and changes in interpersonal contact (71.1%) to be
      responsible, the latter being described as a situation in which people do not
      have time for each other. In view of the importance of social relations for the
      well-being of the elderly, relations between the generations should remain on the
      agenda as a subject for further research and preventive conceptions.

PMID- 9026347
TI  - [Globalization processes promote intercultural gerontology].
AB  - In Germany researchers pay less attention to problems of culture and aging than
      in the USA. This work focuses on international relationships and development, and
      points out the necessity for cross-cultural perspectives.

PMID- 9026348
TI  - [Health and illness in aging. Deficits and perspectives in health care research].
AB  - The health condition of the aging and the future development of healthy aging are
      relevant factors for science, health policy planning and practice. Articulate
      knowledge about epidemiological developments as well as insight into the health
      and functioning of older persons are prerequisites to determine the required
      resources to enable a healthy future of this population group. Demands and
      supplies should be balanced in the context of the available resources and
      identified deficits in the existing health services. The availability, the
      variety and quality of social-, nursing- and medical resources determines to a
      large extent the conditions and perspectives of an older person in case of
      chronic illness. These resources also influence the effectiveness or barriers in
      the prevention of disease and the successful planning of rehabilitation. This
      article presents a critical analysis of the existing health services resources in
      the context of an inadequate development of gerontological and nursing science
      research and research infrastructure. This knowledge is needed to assess the
      anticipated and identified needs of healthy and diseased older persons. In
      addition, emerging perspectives are described and required demands stated, which
      are related, among others to the establishment of research institutions, an
      increasing transfer from science to clinical practice, the realization of these
      perspectives in healthy policy planning and consequently the innovation of
      (professional) practice.

PMID- 9026349
TI  - Mechanism of action of platelet-derived growth factor.
AB  - More than 20 years ago, platelet-derived growth factor (PDGF) was identified and
      later purified. Through recent years of intense research, a large body of
      information has been collected on how PDGF transduces its biological effects to
      responding cells. Two homologous receptors, the PDGF alpha- and beta-receptors,
      have been identified, which are receptor tyrosine kinases. Binding of PDGF leads
      to activation of the kinase and autophosphorylation. Particularly in the PDGF
      beta-receptor, a considerable number of autophosphorylation sites have been
      identified, which allow for physical interaction with signal transduction
      molecules. The signal transduction molecules are often enzymes, which undergo
      activity changes in conjunction with binding to the receptor. Other signal
      transduction molecules function as adaptors, which can couple to subunits
      equipped with catalytic activity. Through the activity changes of inherent or
      directly coupled catalytic activities, a signal is propagated, which ultimately
      results in a cellular response. PDGF is known to induce migration, proliferation
      and differentiation of different cells types. An array of signal transduction
      molecules has been shown to interact with the PDGF beta-receptor; several appear
      to contribute to the generation of the proliferative response, indicating the
      existence of parallel pathways for this response, which are utilized by many
      different growth factor receptors. Migration of cells towards PDGF appears to be
      more strictly dependent on activation of phosphatidylinositol 3' kinase.
      Interestingly, the PDGF alpha-receptor emits negative signals that inhibit
      simultaneous positive signals for migration induced by this receptor, or by other
      receptors, such as the PDGF beta-receptor. Virtually nothing is known about
      signal transduction initiated by PDGF, which generates differentiation responses.
      Since PDGF appears to play a role in different physiological and pathological
      processes, it is important to continue delineation of signal transduction
      pathways initiated through activation of the PDGF receptors.

PMID- 9026350
TI  - Transcription factors and the cardiac gene programme.
AB  - During the past decade, major advances have been made in uncovering the
      mechanisms that switch genes on and off. Gene methylation and histones play an
      important role in gene (in)activation. Following gene activation, the initiation
      of transcription by RNA polymerase requires the assembly of multiple protein
      complexes on the promoter region of a gene. How a cell type-specific gene
      expression pattern can be induced is a key question in cardiovascular biology
      today. Members of the helix-loop-helix-family of the transcription factors play a
      dominant role in skeletal muscle formation. In cardiac muscle the situation is
      less obvious. Recent studies identified muscle transcription factors like MEF-2,
      TEF-1 and MNF, which are common to both the skeletal and cardiac muscle lineages.
      A few transcription factors, among which Nkx 2.5 and GATA-4, are expressed
      predominantly in the heart. The absence of master regulators in the heart points
      to the importance of interaction between ubiquitous factors and tissue restricted
      factors to initiate the cardiac gene programme and to lock these cells in their
      differentiated state. The recent development of murine transgenic and gene
      targeting technology provides tools to study the role of mammalian transcription
      factors in vivo. Interesting cardiac phenotypes are found in gene targeted mice,
      indicating a crucial role for retinoic acid and homeobox genes in murine
      cardiogenesis.

PMID- 9026351
TI  - Novel monohydroxamate drugs attenuate myocardial reperfusion-induced arrhythmias.
AB  - The novel monohydroxamates N-methyl hexanoylhydroxamic acid, N-methyl
      acetohydroxamic acid, and N-methyl butyrohydroxamic acid have antioxidant and
      iron chelating properties. They attenuated reperfusion-induced contractile
      dysfunction following long periods of ischaemia (50 min) in the isolated rat
      heart. Here we compare their effects and that of the trihydroxamate
      desferrioxamine on reperfusion-induced arrhythmias following short duration
      ischaemia (10 min). Isolated rat hearts were perfused by the Langendorff method,
      subjected to regional ischaemia and reperfusion. Arrhythmias induced during the
      first 5 min of reperfusion were quantified. Drugs (all at 150 microM) were
      introduced during the last 2 min of ischaemia and remained throughout
      reperfusion. Although the monohydroxamate- and desferrioxamine-treated hearts
      showed a reduction in the incidence of ventricular tachycardia and fibrillation,
      only the reduction in the incidence of sustained fibrillation ( > 3 min duration)
      in N-methyl acetohydroxamic acid--(27%), N-methyl hexanoylhydroxamic acid--(27%)
      and desferrioxamine-treated hearts (20%) was statistically significant (p < 0.05
      vs control 73%; n = 15). There was a reduction in the severity of the
      arrhythmias, manifest as a significant increase in the duration of sinus rhythm
      in all the monohydroxamate-treated hearts, and a significant reduction (vs
      control 218 +/- 29 s; mean +/- SEM) in the duration of ventricular fibrillation
      in hearts treated with N-methyl acetohydroxamic acid (101 +/- 31 s) and
      desferrioxamine (112 +/- 30 s). This improvement was offset by an increase in the
      duration of ventricular tachycardia, in hearts treated with N-methyl
      acetohydroxamic acid, N-methyl butyrohydroxamic acid and desferrioxamine. These
      results suggest that these novel monohydroxamates, particularly N-methyl
      acetohydroxamic acid, attenuate reperfusion-induced arrhythmias in this model
      when introduced during the ischaemic period.

PMID- 9026352
TI  - Mechanistic studies on uroporphyrin I-induced photoinactivation of some heme
      enzymes.
AB  - Aerobic and anaerobic studies have demonstrated that uroporphyrin I-induced
      inactivation of delta-aminolevulinic acid dehydratase, porphobilinogenase,
      deaminase and uroporphyrinogen decarboxylase was dependent on oxygen and mediated
      by reactive oxygen species. The mechanism of photoinactivation of those heme
      enzymes from human erythrocytes by uroporphyrin I by u.v. light was investigated.
      Enzymes of the heme pathway were preincubated in the presence of specific
      scavengers for several reactive oxygen species and then exposed to uroporphyrin I
      and u.v. light. Upon exposure of the enzymes to the porphyrin under u.v. light,
      and in an aerobic atmosphere, the percentage of enzyme activities with respect to
      the corresponding controls were 50.2 +/- 5.1 (SD, n = 6), 25.3 +/- 3.0 (SD, n =
      6), 25.9 +/- 2.8 (SD, n = 6) and 49.7 +/- 7.5 (SD, n = 8) for delta
      aminolevulinic acid dehydratase, porphobilinogenase, deaminase and
      uroporphyrinogen decarboxylase, respectively. The presence of sodium azide,
      histidine or superoxide dismutase did not protect the enzymes against the effects
      of uroporphyrin I. However, both cysteine and potassium ferrycyanide prevented
      the enzyme photoinactivation induced by uroporphyrin I. In the presence of either
      catalase or GSH, the enzyme photoinactivation was lower. Ethanol, glucose and
      dimethylsulfoxide had no effect on enzyme activity, while ion chelators had
      variable effects. This study shows that the type II mechanism is not the
      predominant reaction mediating the uroporphyrin I effect and enzyme
      photoinactivation would involve an electron transfer. Hydrogen peroxide and
      hydroxyl radicals could possibly mediate the uroporphyrin I-induced enzyme
      photoinactivation.

PMID- 9026353
TI  - Differential solubilization of osteoblastic alkaline phosphatase from human
      primary bone cell cultures.
AB  - Mineralization of cartilage and bone requires alkaline phosphatase activity. In
      order to study the enzymatic properties of bone alkaline phosphatase in bone
      disease and more particularly in patients with osteoporosis and osteoarthritis,
      we investigated the solubilization of alkaline phosphatase from primary bone cell
      cultures derived from human bone explants. To study the release of alkaline
      phosphatase from membranes, several detergents at a concentration above the
      critical micellar concentration and cholesterol were used. Solubilized alkaline
      phosphatase was characterized by enzymatic activity and electrophoresis analysis.
      Almost all the alkaline phosphatase was solubilized using non-ionic detergent as
      n-octylglucoside and hecameg. In comparison with initial membranous activity, the
      solubilized activity was increased by a factor, i.e. 2 +/- 0.05 (SEM, n = 3)
      (with n-octylglucoside), i.e. 2.1 +/- 0.05 (SEM, n = 3) (with Hecameg). With an
      ionic detergent (sodium dodecylsulfate), zwitterionic detergent ((cholamido
      propyl) dimethylammonio 1 propane sulfonate) and cholesterol, a fraction of
      alkaline phosphatase was resistant to solubilization. Electrophoresis studies
      showed that released alkaline phosphatase was a glycosylphosphatidylinositol
      protein (amphipatic form) with 140 kDa as apparent molecular weight. A
      hydrophilic form was obtained by treatment with a specific lipase. This study
      showed differential solubilization of osteoblastic alkaline phosphatase from
      human primary bone cell cultures. Better extractibility and higher activation of
      this membrane anchored enzyme were obtained with non-ionic detergents.

PMID- 9026354
TI  - Effect of insulin on triacylglycerol synthesis and secretion by chicken
      hepatocytes in primary culture.
AB  - A primary culture system of chicken hepatocytes was developed to study the
      effects of genetic, hormonal and nutritional factors on hepatic triglyceride (TG)
      secretion in the chicken, and the effect of insulin on TG synthesis and secretion
      examined. TG synthesis and secretion was measured using [3H]-glycerol
      incorporation into cellular and secreted TG. An additional step consisting of
      brief incubation of the monolayer with trypsin solution to improve harvesting the
      medium immediately adjacent to the cell monolayer, is also proposed. In our
      culture system, TG secretion occurred at least up to 75 hr of culture, showing a
      maximum between 40 and 60 hr of culture. No significant effect of insulin could
      be observed after 24 hr of culture. A clear stimulatory effect was observed with
      10(-9) M insulin concentration after 48 hr. The mean ratio of the secretion rates
      in the presence or absence of insulin was 2.20 +/- 0.30 (SEM, n = 4). In
      contrast, the 10(-6) M concentration of insulin had no effect on TG secretion.
      The use of an additional trypsinization step enhanced the findings obtained by
      simple removal of the culture medium: a clear stimulatory effect of insulin on TG
      synthesis was observed after both 24 and 48 hr of culture. Analysis of TG fatty
      acid composition showed an imbalance of monoene versus saturated fatty acids
      between cellular and secreted TG, secreted TG being more monounsaturated than
      cellular TG. These results were obtained in the absence of exogenous fatty acid.
      An oleic acid supplement in the culture medium did not significantly influence TG
      secretion. In summary, a primary culture system for chicken hepatocyte was
      developed. A high level of TG secretion was seen in these cells with or without
      exogenous fatty acid and this secretion was stimulated by insulin. It was
      concluded that chicken hepatocytes in primary culture provide a useful model for
      studying regulation of TG secretion.

PMID- 9026355
TI  - Purification and characterization of a novel membrane-bound form of prolyl
      endopeptidase from bovine brain.
AB  - Prolyl endopeptidase has been predominantly described as a cytosolic activity
      capable of cleaving a number of important neuropeptides (including TRH, LHRH,
      Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on
      the carboxy side of proline. In this paper, we report, for the first time, on the
      complete purification and characterization of a membrane-bound form of prolyl
      endopeptidase. This novel activity has been isolated from the synaptosomal
      (plasma membranes) membranes of bovine brain. Following gel filtration,
      hydroxylapatite and hydrophobic interaction chromatographies, the prolyl
      endopeptidase activity was purified 1400-fold with a 23% recovery of activity.
      The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60
      microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme
      demonstrated a relatively broad substrate specificity and a relatively high
      affinity for proline-containing neuropeptides. It was shown to be inhibited by
      certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline,
      thus possibly classifying it as a 'thimet' activity. The purified particular form
      of proyl endopeptidase displayed a similar substrate specificity to the
      previously reported cytosolic forms of the enzyme. However, there were
      differences between the two forms in term of their sensitivity to inhibitors,
      their affinities for the peptide substrates and their relative molecular masses.
      The different subcellular location (i.e. the synaptosomal membrane) of the
      particulate prolyl endopeptidase is also of potential physiological significance
      given that here it is more likely to come in contact with the vesicle-bound
      neuropeptides than is its cytosolic counterpart.

PMID- 9026356
TI  - Peptide degradation: effect of substrate phosphorylation on aminopeptidasic
      hydrolysis.
AB  - The effect of substrate phosphorylation on the susceptibility to exopeptidasic
      attack by leucyl aminopeptidase of swine kidney, alanyl aminopeptidase from human
      liver and aminopeptidase N of Escherichia coli was investigated using a synthetic
      heptapeptide (L-R-R-A-S-L-G) and its phosphorylated derivative. The enzyme
      catalyzed products were analyzed by thin layer chromatography and
      electrophoresis. The sensitivities of peptide and phosphopeptide to leucyl
      aminopeptidase digestion were then compared. Data obtained indicated that when
      phosphopeptide was used as substrate one main product accumulated, which
      corresponded to the fragment A-S(P)-L-G, while unphosphorylated peptide was
      completely degraded to its constituent amino acids. Identical results were
      obtained using aminopeptidase N of E. coli. Using alanyl aminopeptidase as
      enzyme, the results obtained were essentially similar, since the exopeptidasic
      activity on the phosphorylated peptide was strongly hampered in the vicinity of
      phosphoseryl residue leading to accumulation of the same phosphorylated product,
      although this enzyme could not completely degrade the unphosphorylated peptide.
      It was concluded that phosphorylation of substrates does effect enzymic
      degradation of proteins.

PMID- 9026357
TI  - Role of kinases and G-proteins on arachidonate release induced by zymosan in
      mouse peritoneal macrophages.
AB  - The present study investigated the role of kinases and G-proteins in arachidonic
      acid (AA) mobilization by resident mouse peritoneal macrophages in response to
      phagocytosis of opsonized zymosan. Stimulation of resident murine peritoneal
      macrophages with opsonized zymosan caused an increase in [3H] arachidonic acid
      release. This increase was dose-dependent and was not accompanied by de novo
      synthesis of proteins. Neither staurosporine, a protein kinase C inhibitor, nor
      genistein, a tyrosine kinase inhibitor, had any effect on [3H] AA mobilization,
      although trifluoperazine significantly inhibited AA release. The involvement of G
      proteins and phospholipase C (PLC) in the regulation of arachidonic acid release
      induced by opsonized zymosan was also examined in mouse peritoneal macrophages.
      Prior treatment of cells with pertussis toxin induced a partial decrease in AA
      mobilization. However, neomycin or aspirin, at doses that inhibit inositol
      phosphate formation (PLC activity), did not [3H] AA mobilization by PLA2. We
      proposed that the AA release by peritoneal macrophages in response to opsonized
      zymosan phagocytosis could be due to the participation of enzymes other than PLC
      and PKC, or proteins other than G proteins.

PMID- 9026358
TI  - No correlation between changes in fatty acid-binding protein content and fatty
      acid oxidation capacity of rat tissues in experimental diabetes.
AB  - Fatty acid-binding protein is considered to play an important role in fatty acid
      oxidation. Since diabetes mellitus causes marked changes of this latter metabolic
      process, we compared the effect of this pathological condition on both parameters
      in a comparative investigation of different rat tissues. Palmitate oxidation
      capacity and content of fatty acid-binding protein were determined in liver,
      heart and quadriceps muscle from rats with 2-week streptozotocin-induced diabetes
      mellitus and controls. In liver homogenates fatty acid oxidation capacity
      increased by 90%, but their content of fatty acid-binding protein decreased by
      35%. Fatty acid oxidation capacity of heart and quadriceps muscle and fatty acid
      binding protein content of quadriceps muscle did not change, but fatty acid
      binding protein content of heart muscle doubled. Long-term diabetes (8 months)
      had a similar effect on content of this protein. In summary, changes of fatty
      acid oxidation capacity do not appear to correlate with fatty acid-binding
      protein content during the development of diabetes. This does not preclude other
      functions of fatty acid-binding proteins in regulation of lipid metabolism and
      processes in which fatty acids play a modulatory role.

PMID- 9026359
TI  - Granulocytic protein p25 is a DNA-binding subunit of protein M(r) = 50,000:
      subcellular localization, cell and species specificity.
AB  - We have previously reported the presence and isolation of the novel protein M(r)
      = 25,000 (p25) from human granulocytes. In this study, the protein p25 was
      characterized by its: (a) ability to bind DNA, (b) subunit association, (c)
      partial protein sequencing, (d) subcellular localization, (e) cellular and
      species specificity and (f) stability in the presence of released granulocytic
      proteinases. For the detection of p25 in various extracts, fractions and types of
      human or animal hematopoietic cells, SDS-PAGE/Western blotting and
      immunohistochemical staining were used. The protein p25 was subjected to N
      terminal amino acid sequence analysis. Protein p25-DNA interactions were
      monitored using Southwestern blotting. Selective inhibition of granulocytic
      proteinases was performed. Granulocytic protein p25 was found to be a product of
      oxidative cleavage of disulfide bridges in the p50 dimer. It was shown that
      neither protein p50 nor the p25 subunit is a degradation product of a protein of
      higher molecular weight. The N-terminal amino acid sequence of p25 was:
      RLNYNKPHAA. Binding capacity for double stranded DNA without significant sequence
      specificity was revealed and nuclear localization of some fraction of p50 dimer
      was established. The data concerning the cell and species specificity
      demonstrated that the protein is expressed only in normal human granulocytes. In
      summary, protein p25 originates from splitting of the p50 dimer. This subunit
      shows no identity with proteins already sequenced. DNA-binding of p25 is not
      sequence specific. It is concluded that the protein p50 is localized in the
      nuclei and cytoplasmic granules of mature human polymorphonuclear leukocytes or
      granulocytes of species high on the evolutionary tree. The functions of this
      protein remain to be determined.

PMID- 9026360
TI  - Comparison of the inhibitory effects of mercury and cadmium on the creatine
      kinase from Electrophorus electricus (L).
AB  - We have determined the effects of mercury and cadmium on the creatine kinase
      activity of the electric organ of Electrophorus electricus (L.) which catalyses
      the transphosphorylation reaction between phosphocreatine and magnesium adenosine
      5'-di-phosphate and has essential sulfhydryl groups. The kinetic effects of these
      heavy metals, which have high affinity for sulfhydryl groups, on the creatine
      kinase activity were analysed with the three reaction components:
      phosphocreatine, adenosine-5'-di-phosphate and magnesium. The kinetic data were
      analysed with a non-linear regression program (Sigmaplot for Windows). Both
      metals inhibit creatine kinase activity in the micromolar range, mercury being a
      more potent inhibitor than cadmium. With phosphocreatine as substrate, mercury
      behaved as a mixed partial hyperbolic inhibitor, non-competitive inhibitor with
      adenosine-5'-di-phosphate, and with magnesium mercury behaved as a competitive
      inhibitor. Cadmium inhibition was shown to be of a classical competitive nature
      with respect to both substrates, phosphocreatine or adenosine-5'-di-phosphate,
      and non-competitive when magnesium was the variable in the reaction mixture. The
      results suggest that the binding site of mercury is at or near the
      phosphocreatine site, but it is not the same as adenosine-5'-di-phosphate,
      whereas cadmium competes with these substrates to bind at the same sulphydryl
      site.

PMID- 9026361
TI  - Spelling of chromone.

PMID- 9026362
TI  - Drug use and drug policy in Hong Kong: changing patterns and new challenges.
AB  - This paper is a sociohistorical examination of drug misuse and drug policy in
      Hong Kong. It briefly traces the history of drug policy since Hong Kong became a
      colony of Britain in the nineteenth century, and then highlights the major drug
      issues that have emerged in the past several decades. Drug policy in Hong Kong
      has gone through three stages, from "Government Opium Monopoly" (1841-1945) to
      "The Prohibition Era" (1946-1960) to "Enlightened Prohibition" (1961-1995). The
      evolution in drug policy is analyzed in the light of both domestic and
      international social, economic, and political forces affecting Hong Kong. The
      major drug issue in the past two decades has been the trends of rising levels of
      drug use among young people and the increasing popularity of psychoactive drugs
      among young drug users. It is argued that these trends may be understood in terms
      of rapid social change resulting from industrialization and socioeconomic growth
      since the 1960s, and the presence of conditions favorable to the demand and
      supply of psychoactive drugs. Lastly, major challenges to future drug policy in
      Hong Kong are discussed.

PMID- 9026363
TI  - [Dens in dente: apicoectomy and retrograde obturation].
AB  - Dens in dente is a developmental anomaly, which, in some advanced cases, requires
      a combination of conventional and surgical endodontic treatment. The purpose of
      this article is to suggest how to treat a Type 3 (Oehlers classification) dens in
      dente.

PMID- 9026364
TI  - Analysis of an alternative promoter that regulates tissue-specific expression of
      the human aromatic L-amino acid decarboxylase gene in cultured cell lines.
AB  - The human aromatic L-amino acid decarboxylase (AADC) gene is transcribed in a
      tissue-specific manner by an alternative promoter. In this study using human
      cultured cell lines, we analyzed the alternative promoter that regulates tissue
      specific expression of AADC. Neither neuronal nor nonneuronal-type mRNA of AADC
      was detected in HeLa cells, nonneuronal-type mRNA of AADC was expressed in HepG2
      cells, and the neuronal-type was expressed in the SK-N-SH cell line. We examined
      the promoter activities located in 5'- and 3'-flanking regions of exon N1 and
      exon L1 by transfection experiments. Plasmids containing 5'-flanking regions of
      exon L1, the shortest of which was 0.3 kb, could promote specifically high
      expression of the reporter gene HepG2 cells. On the other hand, plasmids
      containing 5'-flanking regions of exon N1 (3.6 kb to 0.5 kb) could promote the
      reporter gene expression not only in SK-N-SH cells but also in HeLa and HepG2.
      More enhanced expression were observed by transfection of plasmids containing
      parts of the first intron in these cell lines. Thus, these results suggest that
      the basal liver-specific promoter activity is located in the 5'-flanking region
      of exon L1 and that the first intron may also be needed for enhanced expression
      rather than determination of cell-specificity.

PMID- 9026365
TI  - Brain monoaminergic and neuropeptidergic variations in human aging.
AB  - The effect of age on the monoamines 5-hydroxytryptamine (5-HT), noradrenaline
      (NA) and dopamine (DA), their metabolites 5-hydroxyindoleacetic acid (5-HIAA),
      homovanillic acid (HVA), 3,4-dihydroxphenylacetic acid (DOPAC), and the 5-HT
      precursor 5-hydroxy-L-tryptophan (5-HTP), together with the peptides neuropeptide
      Y (NPY), somatostatin (SOM), and corticotropin-releasing factor (CRF), was
      studied in frontal cortex, gyrus cinguli and hypothalamus from 23 healthy control
      subjects, aged 16-75 years. After correcting for postmortem interval, significant
      decreases in gyrus cinguli NA, NPY and CRF, and hypothalamic DA, HVA, and 5-HIAA
      concentrations were obtained with advancing age. The involvement of the
      monoaminergic system in several functional abnormalities appearing in senescence
      is suggested. Furthermore, evidence is given of the participation of the
      peptidergic systems in the aging process.

PMID- 9026366
TI  - Concurrent locomotor stimulation and decrease in dopamine release in rats and
      mice after treatment with the competitive NMDA receptor antagonists D-CPPene and
      CGS 19755.
AB  - The present study was aimed at investigating the effects of the competitive N
      methyl-D-aspartate (NMDA) receptor antagonists D-CPPene (3-(2-carboxypiperazine-4
      yl)-propenyl-1-phosphonic acid) and CGS 19755 (cis-4-(phosphonomethyl)piperidine
      2-carboxylic acid) on dopamine (DA) transmission and motor activity in mice and
      rats. As measures of DA release we used mouse brain 3-methoxytyramine (3-MT)
      levels, and indirect estimate of DA release, and striatal dialysate measures of
      DA in conscious and freely moving rats by means of microdialysis. To obtain
      additional information about monoaminergic neurotransmission, brain tissue levels
      of DA, DOPAC, HVA, 5-HT and 5-HIAA were measured in both mice and rats. The
      animals were sacrificed at the time when NMDA antagonist-induced locomotor
      stimulation was maximal. In mice, D-CPPene and CGS 19755 decreased striatal 3-MT
      levels, whereas, in general, 3-MT levels in the limbic forebrain were not
      significantly altered. Treatment with CGS 19755 decreased rat striatal dialysate
      levels of DA but increased 5-HIAA at time points when locomotor activity was
      increased. D-CPPene and CGS 19755 have been observed to produce psychotic
      symptoms in man. The present study suggests that these symptoms are not a result
      of an increase in central dopamine release.

PMID- 9026367
TI  - The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK
      801, a non-competitive NMDA receptor antagonist.
AB  - It was found previously that the MK-801 (an uncompetitive NMDA receptor
      antagonist)-induced locomotor hyperactivity in rats was potently increased by
      antidepressant drugs. The present paper analysed the locomotor hyperactivity
      induced by combined treatment with fluoxetine + MK-801 in male Wistar rats. The
      MK-801 hyperactivity was increased by citalopram (the latter effect was prevented
      by zacopride and ketanserin), sertraline, p-chloramphetamine, 8-OH-DPAT and
      TFMPP. The hyperlocomotion caused by fluoxetine + MK-801 was antagonized by
      tropisetron and zacopride and, to a lesser extent, by ketanserin, ritanserin and
      NAN-190, but not by WAY 100135, pindolol, metergoline or mianserin. Sulpiride and
      clozapine were able to inhibit the fluoxetine + MK-801 hyperlocomotion. The
      hyperlocomotion induced by D-amphetamine or apomorphine was not modified by
      fluoxetine or citalopram. Fluoxetine increased the release of dopamine (measured
      by a microdialysis method) in the striatum, induced by MK-801. The obtained
      results indicate that fluoxetine increases the MK-801-induced locomotor
      hyperactivity via activation of 5-HT3 receptors and, to a lesser degree, 5-HT2
      ones.

PMID- 9026368
TI  - Hippocampal histamine receptors: possible role on the mechanisms of memory in the
      rat, II.
AB  - In this paper it was studied the role of histamine and histamine receptors in the
      hippocampus of rats on an active avoidance response induced by an ultrasonic
      tone. The animals had to learn to walk through a swinging door into a safe
      compartment only after the conditioning ultrasonic tone was on in order to avoid
      an electric shock to their feet. Trained animals were implanted in the ventral
      hippocampus with microinjection cannulae and injected twice with 1 microliter of
      saline solution containing pyrilamine (PYR, H1-HA antagonist), ranitidine (RAN,
      H2-HA antagonist) or histamine. The histamine antagonists were applied in a dose
      of 65.5 nmol each while histamine was administered in a dose of 45 nmol. The two
      variables measured were the time in sec the rats take to present the conditioned
      avoidance response and the accumulated percentage of conditioned avoidance
      response (CAR). Results showed that histamine administration significantly
      increased the latency time to escape and decreased the % CAR. These effects were
      not blocked by the administration of RAN. However, administration of PYR
      completely counteracted the HA effects. Present findings confirm our previous
      findings about the inhibitory effect of histamine on the hippocampal retrieval
      mechanisms and give further support to the hypothesis that HA acts on the memory
      processes in the hippocampal formation, by activation of H1-histamine receptors.

PMID- 9026369
TI  - Decreased plasma ratio of tryptophan to competing large neutral amino acids in
      human immunodeficiency virus type 1 infected subjects: possible implications for
      development of neuro-psychiatric disorders.
AB  - Those large neutral amino acids (LNAA) which compete with each other for the
      carrier mediated transport from plasma into the brain were determined in plasma
      in human immunodeficiency virus (HIV-1) seropositive subjects and seronegative
      controls. Previous findings of a decreased concentration of tryptophan were
      confirmed whereas no difference between HIV-1 seropositive subjects and controls
      were found in those LNAAs with which tryptophan competes for the transport into
      the brain. Thus, the ratio in plasma of tryptophan to the total LNAA
      concentration was decreased in HIV-1 seropositive subjects. This ratio is
      considered to, at least partly, regulate the availability of tryptophan in the
      brain. Since tryptophan is a precursor to the neurotransmitter 5-HT and since the
      enzymes involved in the 5-HT synthesis normally are not saturated, the decreased
      plasma ratio of tryptophan might cause a decrease in brain 5-HT synthesis and,
      thus, to an impaired function in brain 5-HT neurons. This mechanism might, as
      well as previously demonstrated accumulation within the brain of the neurotoxic
      tryptophan metabolite quinolinic acid, contribute to the development of dementia
      and other neuro-psychiatric disorders, often seen in AIDS patients. Treatment
      with 5-HT receptor agonists might prove effective to prevent neuro-psychiatric
      disorders.

PMID- 9026370
TI  - Serotonin 5-HT3 receptor binding kinetics in the cortex of suicide victims are
      normal.
AB  - Serotonergic abnormalities have been identified in the brain of suicide victims
      independent of psychiatric diagnosis. We report the first study of serotonin 5
      HT3 receptors in the brain of suicide victims. There were no differences in the
      number (Bmax) or affinity (KD) of 5-HT3 receptors in the temporal cortex of
      suicide victims compared to matched controls. There was a negative correlation
      between brain serotonin levels and receptor number (r = -0.5, p = 0.04) in both
      groups. This study indicates that alterations in serotonergic function in the
      brain of suicide victims do not appear to directly involve the 5-HT3 receptor.

PMID- 9026371
TI  - SDZ GLC 756, a novel octahydrobenzo[g]quinoline derivative exerts opposing
      effects on dopamine D1 and D2 receptors.
AB  - SDZ GLC-756, a novel octahydrobenzo[g]quinoline derivative, is equipotent in
      displacing [3H]SCH23390 from dopamine D1 receptors and [3H]205-501 from dopamine
      D2 receptor binding sites. It blocks dopamine sensitive adenylate cyclase with
      the same potency as SCH23390, indicating antagonist properties at dopamine D1
      receptors. On the other hand, SDZ GLC 756 inhibits electrically evoked
      acetylcholine release from rat striatal slices with the same potency as the
      selective dopamine D2 receptor agonist bromocriptine. This effect is blocked by
      spiperone suggesting that it is mediated by dopamine D2 receptor activation. The
      opposing action of SDZ GLC 756 on dopamine D1 and D2 receptors is also evident in
      vivo. SDZ GLC 756, like SCH23390, blocks apomorphine-induced rearing in mice. On
      the other hand, it inhibits prolactin secretion and produces circling in
      unilateral 6-OHDA-lesioned rats, which is compatible with stimulant properties at
      dopamine D2 receptors. This drug might be a new tool to study linkage between
      dopamine D1 and D2 receptors.

PMID- 9026372
TI  - Serotonin (5-HT) release in the dorsal raphe and ventral hippocampus: raphe
      control of somatodendritic and terminal 5-HT release.
AB  - Somatodendritic and terminal release of serotonin (5-HT) was investigated by
      simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3
      acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphe and ventral
      hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1 microM and
      10 microM) into the dorsal raphe simultaneously decreased dorsal raphe and
      hippocampal 5-HT release. However, following TTX perfusion into the hippocampus
      (10 microM), hippocampal 5-HT release was profoundly reduced but dorsal raphe 5
      HT remained unchanged. Systemic injections with 5-HT1A agonist, buspirone (1.0
      5.0 mg/kg, i.p.) decreased 5-HT and 5-HIAA and increased HVA concentrations in
      the dorsal raphe and in the hippocampus. The decreases in the raphe and
      hippocampal 5-HT induced by systemic buspirone were antagonized in rats
      pretreated with 1.0 mM (-) pindolol, locally perfused into the dorsal raphe.
      Local dorsal raphe perfusion of (-) pindolol alone (0.01-1.0 mM) increased dorsal
      raphe 5-HT and concomitantly induced a small increase in hippocampal 5-HT.
      Buspirone perfusion into the dorsal raphe did not change (10 nM, 100 nM), or
      produced a small increase (1.0 mM) in raphe 5-HT, without changing hippocampal 5
      HT. These data provide evidence that 5-HT release in the dorsal raphe is
      dependent on the opening of fast activated sodium channels and that dorsal raphe
      5-HT1A receptors control somatodendritic and hippocampal 5-HT release

PMID- 9026373
TI  - Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing
      tianeptine and -inhibiting fluvoxamine utilizing EEG mapping and psychometry.
AB  - In a double-blind, placebo-controlled study, the encephalotropic and psychotropic
      effects of tianeptine (TIA)--a new tricyclic antidepressant, enhancing serotonin
      reuptake--were investigated as compared with the serotonin reuptake inhibiting
      antidepressant, fluvoxamine (FLU), utilizing EEG mapping, psychometric and
      psychophysiological measures. 16 healthy volunteers (8 males, 8 females) aged 21
      35 (man 27) years received randomized and at weekly intervals single oral doses
      of placebo, 12.5 and 25 mg TIA and 50 mg FLU. EEG recordings, psychometric and
      psychophysiological tests and evaluation of pulse, blood pressure and side
      effects were carried out at 0, 2, 4, 6 and 8 hours; blood sampling, in addition,
      at hour 1. TIA plasma levels rose fast to peaks at 1-2 hours and declined rapidly
      as well, while the MC5 metabolite peaked in the 4th hour and declined more
      slowly. EEG mapping demonstrated that both TIA and FLU induced significant
      changes in brain function between the 1st and 8th hour, which, however, differed
      in their time course. 12.5 mg TIA exhibited, as compared with placebo, slight
      activating properties in the EEG (decrease of delta and theta, increase of alpha
      and beta, acceleration of the centroid), parallelled by thymopsychic improvement
      (mood elevation). 25 mg TIA showed EEG activation up to the 4th hour, later EEG
      sedation, accompanied by an initial thymopsychic improvement and differential
      changes thereafter (improved mood, decreased vigility), with the noopsyche
      improving at all times (attention, Pauli test). 50 mg FLU induced initially
      sedation and thereafter activation, accompanied by thymopsychic deterioration and
      subsequent improvement, the latter also being observed in the noopsyche
      (attention, memory). In pupillary and skin conductance measures, generally a
      slight activation occurred after placebo, which was attenuated by 25 mg TIA.
      Correlation maps between plasma levels and EEG changes demonstrated: the higher
      the TIA plasma levels, the more absolute and relative beta power, the less alpha
      power and the faster the centroid of the total power spectrum, reflecting CNS
      activation. Topographically, the correlations were mostly seen over both fronto
      temporal regions. In the latter, dominant frequency signalled desactivation in
      the right and activation in the left hemiphere after both antidepressants which,
      thereby induced changes in brain function opposite to those observed in
      depression. Both drugs were well tolerated.

PMID- 9026374
TI  - Brofaromine--a review of its pharmacological properties and therapeutic use.
AB  - The antidepressant activity of monoamine oxidase inhibitors has been well
      established for 30 years. Nevertheless, this group of compounds was handled with
      great care, mainly because of the interaction potential with tyramine-containing
      foodstuff. With the discovery of reversible and selective inhibitors of monoamine
      oxidase type A a renaissance of these compounds has begun. In this paper one of
      these new substances--brofaromine--will be described in detail. Biochemical and
      pharmacological aspects will be reviewed, showing that brofaromine is a selective
      and reversible inhibitor of monoamine oxidase type A with additional serotonin
      reuptake inhibiting properties. Both mechanisms of action may synergize in the
      antidepressant effect of the compound. The main results of clinical trials in
      depression and other indication areas will also be covered. Special attention
      will be put on the side effect profile.

PMID- 9026375
TI  - Glutamate receptor activation induces carrier mediated release of endogenous GABA
      from rat striatal slices.
AB  - The regulation of striatonigral and striatopallidal GABAergic neurons by
      glutamatergic afferents is thought to play a critical role in normal basal
      ganglia function. Here we report that in striatal slices about 17% of K(+)
      induced endogenous GABA release was Ca(2+)-independent and this could be blocked
      by a GABA transport inhibitor. Activation of N-methyl-D-aspartate (NMDA)- and
      quisqualate-sensitive receptors induced endogenous GABA efflux only in the
      presence of a GABA transaminase inhibitor; this efflux was inhibited by 60-80%
      with a GABA transport inhibitor. NMDA-induced GABA release was blocked by
      phencyclidine, Mg2+ and CGS 19755. Quisqualate-induced GABA release was blocked
      completely by a combination of the metabotropic antagonist, L-AP3 and CNQX, a non
      NMDA receptor antagonist. These data indicate that excitatory amino acid agonists
      induced GABA release is distinct from that induced by high K+ depolarization.

PMID- 9026376
TI  - Characterization of [3H]pentazocine binding sites in post-mortem human frontal
      cortex.
AB  - We investigated binding characteristics of [3H](+)-pentazocine in homogenates of
      post-mortem human frontal cortex. At equilibrium, specific binding was linear
      with protein concentration, was saturable, reversible, stereoselective, heat
      labile and was nearly absent in the white matter. Saturation experiments revealed
      a KD of 3.68 +/- 0.46nM and a B(max) of 0.636 +/- 0.107 pmol/mg protein. The rank
      order of Ki values of competing substances was: haloperidol < N,N'-di(o
      tolyl)guanidine (DTG) < (+)-SKF 10,047 < (-)-SKF 10,047. We also examined the
      influence of age, gender, hemisphere, post-mortem time and storage time of brain
      tissue at -80 degrees C on [3H](+)-pentazocine binding sites. Of these variables,
      only age was significantly related to [3H](+)-pentazocine binding (diminished
      binding with increasing age). Together, our results demonstrate the presence of
      specific [3H](+)-pentazocine binding sites in post-mortem human brain tissue.
      Furthermore, the binding sites decrease with increasing age and are apparently
      independent of gender, hemisphere, post-mortem time and storage time of brain
      tissue.

PMID- 9026377
TI  - Alcohol exposure during development alters hypothalamic neurotransmitter
      concentrations.
AB  - The effect of exposure to alcohol during a period roughly equivalent to the human
      third trimester on neurotransmitter content in the rat hypothalamus was examined.
      The alcohol exposure was accomplished via an artificial rearing procedure. The
      alcohol group was exposed to 5 g/kg/day of ethanol from postnatal day (PD) 4 to
      10. There was an artificially reared control group not exposed to alcohol and a
      normally reared control group. Noradrenaline, dopamine, homovanillic acid (HVA),
      3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindoleacetic acid
      (5-HIAA) concentrations were measured using high performance liquid
      chromatography with electrochemical detection in juvenile and adult rats. There
      were no effects in juvenile rats. In adult rats, alcohol exposure from PD 4 to 10
      increased hypothalamic content of noradrenaline, dopamine, serotonin and 5-HIAA.
      While adult females had greater amounts of hypothalamic serotonin and 5-HIAA than
      adult males, there were no interactions of sex with alcohol exposure. These
      results suggest that hypothalamic function is seriously disrupted by alcohol
      exposure during development.

PMID- 9026378
TI  - TJS-010, a new prescription of oriental medicine, enhances 8-OH-DPAT-induced
      effects in rats.
AB  - We evaluated the effect of TJS-010, a new prescription of oriental medicine, on
      hypothermia and flat body posture in rats, induced by activation of serotonin (5
      HT)-1A receptors by (+/-)-8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT).
      Hypothermia was induced by 8-OH-DPAT in a dose and time-dependent manner. The
      hypothermia induced by 0.1 mg/kg 8-OH-DPAT was enhanced by 500 and 750 mg/kg of
      TJS-010. At the concentration of 0.1 mg/kg, 8-OH-DPAT also produced flat body
      posture in rats, and 750 mg/kg TJS-010 increased the flat body posture. These
      results suggest that TJS-010 facilitates the 5-HT-1A receptors in the central
      nervous system.

PMID- 9026379
TI  - Effect of pindolol on hormone secretion and body temperature: partial agonist
      effects.
AB  - Pindolol has been shown to be a partial agonist at 5-HT1A receptors in
      preclinical studies. It has also been reported to inhibit the effects of other 5
      HT1A partial agonists such as ipsapirone and buspirone on hormone secretion and
      body temperature in man, indicating its antagonist action at 5-HT1A receptors in
      man. To determine if pindolol has 5-HT1A agonist as well as antagonist effects in
      man, pindolol, 30 mg, p.o. and placebo, were given single blind in random order
      to 23 normal men with indwelling venous catheters and its effects on hormone
      secretion and body temperature noted. Pindolol significantly increased basal
      plasma cortisol concentrations, whereas it decreased plasma prolactin (PRL)
      concentrations and body temperature. The increase in plasma cortisol due to
      pindolol suggests a 5-HT1A agonist action and is consistent with a 5-HT1A partial
      agonist mechanism in man whereas the PRL effects are consistent with an
      antagonist action at 5-HT1A receptors. The effects of pindolol on plasma cortisol
      concentration and body temperature were significantly negatively correlated.
      Furthermore, these results indicate significant differences in the 5-HT1A
      dependent regulation of PRL and the hypothalamo-pituitary-adrenal (HPA) axis and
      body temperature, and suggest that human basal PRL secretion is tonically
      stimulated by 5-HT1A mechanism whereas the HPA axis and body temperature are not.
      Since rodent studies suggest differences in 5-HT1A receptor sensitivity between
      males and females, the results reported here need to be replicated in females.
      These differences in the effect of pindolol are discussed in terms of receptor
      reserve theory.

PMID- 9026382
TI  - [The possibility of nonenzymatic prothrombin activation during free-radical
      oxidation].
AB  - The existence of the prothrombin unenzymic activation by free oxygen radicals is
      experimentally proved. It has been found out that the 30-min-long action of free
      radicals generated by the ferrum-ascorbic system induced the thrombin activity.
      The HPLC-spectrum of this reaction mixture demonstrated four new fractions. A
      conclusion is made that there is an accidental system in the body responsible for
      the activation and degradation of bioactive substances.

PMID- 9026381
TI  - [Reparative phenomena in acute infectious inflammation].
AB  - On the model of peritonitis induced by E. coli in rats the regularities of repair
      in dynamics of acute infectious inflammation and post-inflammatory regeneration
      have been studied. The peaks of neutrophils, macrophages, immature fibroblasts
      and restoration of mature fibroblasts number in mesenterium on the 1, 3, 5, and
      10th days, respectively, have been found. The synthetic functional activity of
      macrophages and fibroblasts reached their peaks in the same terms. The increased
      activities of macrophages up to the 90th day, immature fibroblasts up to the 30
      60th day and mature fibroblasts up to the 60-90th day have been marked.

PMID- 9026380
TI  - Effect of adrenalectomy and corticosterone substitution on glucose and glycogen
      metabolism in rat brain.
AB  - In non-nervous tissues, glucocorticoids (GCs) counteract the effects of insulin
      and stimulate gluconeogenesis. The present study was designed to investigate
      whether or not adrenalectomy (ADX) and glucocorticoid substitution influence the
      pathway of both glucose and glycogen metabolism in cerebral parietotemporal
      cortex and hippocampus, and if so how. The activities of respective key enzymes,
      such as hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), glucose
      6-phosphatase (G6Pase) and phosphorylase a (PLa), and the concentrations of the
      intermediates, such as glucose (Glu), glucose-6-phosphate (G6P), fructose-6
      phosphate (F6P), fructose-1,6-bisphosphate (F16PP), pyruvate (Pyr), lactate
      (Lac), glycogen (Glyc) and glucose-1-phosphate (G1P), were measured in the brains
      of 1-year-old male Wistar rats under controlled conditions 3 days after ADX or
      sham operation and in a pilot study after ADX and substitution with
      corticosterone (CST) suspended in sesame oil or after ADX and subcutaneous
      administration of the vehicle only. An increase in both glycolytic flux and
      glycogen breakdown and a decrease in gluconeogenesis in cerebral cortex but not
      in hippocampus were observed after ADX. After substitution with CST in
      adrenalectomized rats the effect of ADX on enzyme activities was reversed:
      significant differences from adrenalectomized rats that received vehicle only was
      shown for PK and G6Pase activities in both areas of the rat brain investigated.

PMID- 9026383
TI  - [The effect of Val'kofen tablets for children on the function of the
      gastrointestinal tract and liver in an experiment].
AB  - It was prepared new child's medicinal form, the tablets "Valcophene" for making a
      wider variety of pediatric preparation's. It is studied the influence of
      "Valcophene" on the functional state of alimentary canal in experiment on rat's.
      Results investigation's are testified to absence of ulcerative action in new
      child's preparations. Studying influence in liver functional state is provided
      for new children's preparation "Valcophene" too. The chronic experiment is showed
      that "Valcophene" didn't influence on liver in experimental animals.

PMID- 9026384
TI  - [A new method for assessing hepatocyte glucuronyl-conjugating function].
AB  - Patients with obstructive jaundice have shown the prevalence of bilirubin
      diglucuronide in the blood serum. This pigment has maximum absorption after the
      process of binitrogenization, the wavelength being 540 nm. The level of bilirubin
      diglucuronide in the blood serum of patients with hepatocellular jaundice was
      reduced. The maximum extinction after binitrogenization is registered when the
      wavelength is 400 nm. This method may be used for assessing a glucuronyl
      conjugative function of hepatocytes.

PMID- 9026386
TI  - [The growth characteristics of the liver parenchyma in the pre- and postnatal
      ontogeny of the guinea pig].
AB  - The growth dynamics of guinea pig liver parenchyma in prenatal and postnatal
      ontogeny was investigated with morphometrical and stereological methods. The
      results show that parenchyma growth in prenatal period is determined by high
      proliferative activity of prehepatocytes, which sizes remain nearly constant. On
      the contrary in postnatal period hepatocytes' hypertrophy becomes the main factor
      of parenchyma growth. The specificity of prenatal liver growth can be determined
      by a necessity to maintain geometrical stability of its "hemopoietic stroma".

PMID- 9026385
TI  - [The effect of transitional metal cations on pepsinogen extrusion by dispersed
      gastric glands].
AB  - It has been found that transient metal cations (Mn2+, Co2+, Cd2+, La3+) cause
      substantial disturbance of pepsinogen extrusion by isolated gastric glands of
      guinea pigs. In low concentrations (10(-5)-10(-4) mol/l) they are found to
      decrease spontaneous and stimulated pepsinogen extrusion by inhibition of Ca2+
      influx into the secretory cells. In high concentrations (10(-3)-10(-2) mol/l)
      metal cations are able either to stimulate (Mn2+, Co2+) or to inhibit (La3+,
      Cd2+) pepsinogen extrusion depending on their type. Their effect is not connected
      with disturbance of calcium transport into the cells.

PMID- 9026387
TI  - [The renal effects of melatonin in intact and epiphysectomized rats].
AB  - Epiphysectomy in adult pubescent Wistar rats causes polyuria and Na uresis at the
      expense of the increased rate of the glomerular filtration and sodium filtration
      charge. Melatonin in a dose of 4.31 mkM/100 g of the body weight increased the
      glomerular filtration of both sodium and water and stimulated the sodium tubular
      transport in rats with intact epiphysis and did not normalize changes of the
      nephron excretory activity after epiphysectomy.

PMID- 9026388
TI  - [The effect of lymphocytic chalone on lymphocyte functional activity in
      antioxidant deficiency and its correction with vitamin E].
AB  - Activity of lymphocyte chalone-tissue-specific inhibitor of cell proliferation
      and its effect on immunocompetent cells in antioxidant insufficiency (AOI) and
      its correction with vitamin E were studied in the work. It was stated that
      lymphocyte chalone quantity in AOI increased 2 times as compared with control
      values and was at the same level when using alpha-tocopherol acetate. The
      inhibiting activity of chalone was preserved in relation to the proliferative
      activity of lymphocytes and disappeared in relation to DNA-synthesis with
      immunocompetent cells. The study of fatty acids spectrum of lymphocyte membrane
      phospholipids has shown that lymphocyte chalone normalized the content of
      saturated and unsaturated fatty acids that demonstrates the antioxidant
      properties of lymphocyte chalone.

PMID- 9026389
TI  - [The psychophysiological functions of students with different achievements in
      flight training].
AB  - Reliable distinctions in parameters of neurodynamic and psychomotoric functions
      in students with different flying advancement, which were markedly manifested
      with presentation and processing of complex information have been established. No
      reliable distinctions were found in other functional parameters.

PMID- 9026391
TI  - [An analysis of the physiological activity of organic compounds of ozokerite
      obtained by its biotransformation by naftusia water microorganisms].
AB  - A possibility to obtain physiologically active substances by means of
      biotransformation of natural carbohydrate raw material-ozokerite using the
      saprophite groups of microorganisms isolated from the medicinal water naftusia
      has been studied. It is shown that microorganisms metabolise ozokerite with
      following formation of the whole spectrum of water-soluble substances, activators
      and inhibitors of Na, K-ATPase, cholopoiesis stimulators being found among them.
      A conclusion has been made that using microorganisms inhabiting water naftusia
      can obtain from ozokerite organic substances conditioning physiologic activity of
      this medicinal water.

PMID- 9026390
TI  - [The neuroendocrine mechanisms of the development of the anovulatory
      hyperandrogenic syndrome in rats].
AB  - The anovulatory syndrome in adult female rats occurred after subcutaneous
      implantation of silastic capsules with testosterone. Acceleration of testosterone
      conversion into estradiol in the hypothalamus, suppression of pituitary LH
      responsiveness to LHRH, increase of blood plasma bioactive LH, estrous cycle
      disorder as well as morphological changes in ovaries demonstrate the alterations
      in neuroendocrine control of ovulation.

PMID- 9026392
TI  - [The characteristics of tissue lipid peroxidation in the internal organs and the
      lipid metabolic indices of the blood plasma in a low geomagnetic field].
AB  - It was found in experiments on guinea-pigs and white rats that 100-time weakened
      magnetic field of the earth considerably increased the activity of peroxide
      oxidation of lipids (POL) in tissues of inner organs. In the lungs, liver,
      kidneys, small intestine under the influence of hypogeomagnetic field (HGMF) we
      have observed reduction of ferment antioxidizing activity and of non-ferment
      mechanisms in the heart. The process is accompanied by reduction of cholesterol,
      phospholipids and triglycerides in guinea-pigs and increase of this indices in
      white rats after 5-day-long stay of animals in the hypogeomagnetic chamber. The
      data of experiments on white rats underlie a conclusion that the 5-day-long
      influence of HGMF promotes the change of the carbohydrate metabolism for lipid
      metabolism. The reaction of guinea-pigs on the stay under the weakened magnetic
      field of the earth displays in reduction of the level of lipid metabolism indices
      in the blood serum.

PMID- 9026394
TI  - [Paracetamol pharmacokinetics in the blood plasma of sexually immature rabbits
      with the use of the new Paravit preparation].
AB  - "Paravit" tablets have been investigated. The pharmacokinetics of "Paravit" was
      studied on preadolescent rabbit. "Paracetamol" tablets were used for comparison.
      The amount of paracetamol was measured in the rabbits plasma using
      spectrophotometry. It is shown that the relative bioequivalence of "Paravit" was
      136.7%.

PMID- 9026393
TI  - [The function of the brain structures in rabbits under the action of hyperbaric
      helium and nitrogen-oxygen mixtures].
AB  - Behaviour of rabbits as well as excitability thresholds of certain brain areas
      were determined by intracranial electrostimulation under high pressure in the
      heliox and nitrox media. Excitability of the mesencephalic reticular formation
      and of the frontal cortex in particular, decreased under 11 ata in the nitrox
      medium. On the contrary, measurements of the thresholds and EEG data have shown
      an increase in excitability in all brain regions under 41 ata of the heliox
      medium. Excitability increased most of all in the dorsal hippocampus and nucleus
      caudatus. The role of different brain structures in the symptomatics of nitrogen
      narcosis and high-pressure nervous syndrome is discussed.

PMID- 9026396
TI  - [The catecholamine content of the hypothalamus during the modelling of the ulcer
      process in the gastroduodenal area].
AB  - The content of catecholamines in rat hypothalamus in experimental ulcer process
      in gastroduodenal region has been studied in experiments on rats. It was
      determined that under these conditions the content of hypothalamus adrenalin
      increases and the content of noradrenalin decreases. The level of dofamin and
      DOFA in this brain structure changes in phases. The mentioned shifts depended on
      the duration and character of the pathological process in the gastroduodenal
      region.

PMID- 9026395
TI  - [The activity of the enkephalinergic systems of the brain and hypophysis in
      experimental hypocorticism].
AB  - Changes in activity of basic components of enkephalinergic system, leu-enkephalin
      contents, activity of enkephalin-hydrolysing enzymes (enkephalinases A and B,
      enkephalin aminopeptidases) and 3H-leu-enkephalin specific binding to opioid
      receptor in rat anterior and mediobasal hypothalamus, striatum, medulla oblongata
      and adenohypophysis have been analysed on experimental models of
      hypocorticoidism. No changes in brain and pituitary body leu-enkephalin contents
      following unilateral hypocorticoidism. No changes in brain and pituitary body leu
      enkephalin contents following unilateral adrenalectomy were shown. Bilateral
      adrenalectomy resulted in two-phase character of neuropeptide level: a decrease
      of leu-enkephalin contents in hypothalamus, striatum and adenohypophysis on the
      7th day and its increase to the normal level on the 10th day after the operation
      were revealed. A decrease of leu-enkephalin contents in rat brain on the 7th day
      following adrenalectomy occurred simultaneously with a decrease in enkephalin
      aminopeptidase activity and specific binding of labeled leu-enkephalin testifying
      to strengthening of enkephalin release form neurosecretory granules of brain
      structures following adrenalectomy. Important changes in leu-enkephalin contents,
      reception and inactive processes on the level of adenohypophysis and on the level
      of hypothalamus, striatum and medulla oblongata were detected by cortisol and
      ACTH administration in adrenalectomised animals.

PMID- 9026397
TI  - [Disorders of myocardial contractile function and the mechanisms of their
      compensation in ischemic heart disease in man].
AB  - Myocardial contractile function was investigated in 84 patients with coronary
      diseases CD of I-IV functional classes (according to NYHA) and 17 persons with
      normal coronary arteries using new noninvasive method of construction LV end
      systolic pressure-volume relation (ESPVR). Significant decrease of end-systolic
      elastance, ejection fraction, circumferential fibers shortening velocity and
      increase of end-systolic and end-diastolic ventricular volume was increased with
      patient's class number. These data correlated with the increase of total amount
      of lesion of coronary vessels and extension of asynergic zones. But this
      contractile function disturbances were not accompanied by significant changes of
      cardiac output and arterial pressure. When blocking beta-adrenergic receptors
      with anaprillin it was established that at early stages of CD the compensation of
      contractile function disturbances is reached via the increasing of heart
      adrenergic stimulation, and in the patients of III-IV classes the Frank
      Starling's law becomes of great significance homo- and heterometric mechanisms
      efficiency reduces with CD development. These data show that ESPVR reconstruction
      before and after the blocking of beta-adrenergic receptors allows systolic LV
      function and efficiency of its regulation to be estimated.

PMID- 9026398
TI  - [The effect of alpha-adrenoblockaders on the lipid complex of the myocardium,
      liver and erythrocytes in dogs with pulmonary heart failure].
AB  - Fatty acid spectrum of phospholipids and free cholesterol level in the
      myocardium, liver and erythrocytes were studied in dogs with the experimental
      lung-heart insufficiency (LHI). The content of polyunsaturated fatty acids of
      phospholipids in erythrocytes from peripheric blood and in free cholesterol level
      (2-3 times) in myocardium, liver and erythrocytes of dogs under investigated
      conditions decreased. It is shown that pharmacotherapy with alpha-adrenoblockers
      (thropaphen and prasozin) has led to the normalization of disturbances of the
      erythrocytic lipid complex and had caused inhibition of peroxidase reactions in
      the myocardium and liver of the dogs with LHI.

PMID- 9026399
TI  - [The osmolar concentrating function of the kidneys under the influence of
      nonspecific transplantation factors against a background of hypercalcemia].
AB  - In experiment on rats functional overload (36 hours of water depression) helps in
      establishing the fact that the kidney subjected to the actions of non-specific
      factors of transplantation (ischemia, denervation, delymphatization) restores its
      ability to keep osmotic haemostasis to the 17th day. The same alterative factors
      against a background of hypercalcemia is not accompanied by the restoration of
      osmoconcentration functions to the 30th day of the experiment. One of the causes
      of this phenomenon may be the increase in the velocity of filtration in the
      kidney.

PMID- 9026400
TI  - [Changes in the energy metabolism in the kidneys of white rats in the dynamics of
      acute sodium nitrate poisoning].
AB  - Experimental study of white rats has shown that the intragastric introduction of
      sodium nitrate at a rate of 9.6 g/kg of their mass is followed by the development
      of considerable disturbances of energy metabolism in kidneys. It was shown that
      the depression and separation of oxidation and phosphorylation, decrease
      energetic potential in the kidney tissues. The results obtained permit supposing
      the significant role of nitric oxide in kidneys as a factor resulting in
      bioenergetic disturbances. Maximum maintenance of Fe-NO complexes was marked 24
      hours after the introduction of sodium nitrate and it corresponded to maximum
      disturbances of energy metabolism.

PMID- 9026401
TI  - [Crystalline cholesterol as a factor in thrombus formation].
AB  - The model using crystalline cholesterol as the thrombogenic process inductor was
      developed. Thrombi that are morphologically equivalent to the human arterial
      thrombi under atherosclerosis were created in experiment on standard animals. It
      was shown that the "head" (conglutinational part) of such thrombi includes the
      thrombocyte mass, organised into the system of branched trabeculae surrounded by
      leucocytal limbus. The "caudal" (coagulational part) of the experimentally
      obtained thrombi consists of fibrin and erythrocytes. Data obtained make it
      possible to consider crystalline cholesterol of atheromatous plaques as the most
      probable trigger factor of thrombogenesis during atherosclerotic process.

PMID- 9026402
TI  - [Use of a mix of lidocaine and butorphanol as a caudal epidural anesthesia in a
      mare].
AB  - Loss of rear motor control is the main limiting factor in the use of caudal
      epidural anesthesia in the horse. In man and laboratory animals, a small dose of
      an opiate combined with a local anesthetic enhances analgesia without impairing
      motor function. Thus, the amount of local anesthetic administered may be reduced.
      Butorphanol is an opiate widely used in horses. It has a good margin of safety
      and few cardiorespiratory effects. The effects of lidocaine (0.25 mg/kg) and
      lidocaine-butorphanol (0.25 mg/kg, and 0.04 mg/kg, respectively) were compared in
      2 groups of 5 healthy unsedated mares. Horses in each group received either
      lidocaine or lidocaine-butorphanol in saline solution for a total volume of
      0.0165 mg/kg. Epidural injection was performed at the first coccygeal interspace.
      Each mare was used only once. Cutaneous analgesia was assessed by a response to a
      pin prick; and visceral analgesia was assessed by response to a noxious stimulus
      applied to the urethra. Heart rate, respiratory rate, and arterial blood pressure
      were also measured. Analysis of the results showed an increase in duration of
      both cutaneous and visceral analgesia in the mares given lidocaine-butorphanol.
      Cutaneous analgesia increased from 36 +/- 13 to 150 +/- 21 min and visceral
      analgesia increased from 22 +/- 10 to 162 +/- 16 min. A cranial extension of the
      cutaneous analgesia was also observed. Cardiorespiratory depression or signs of
      excitation were not observed. However, these mares demonstrated peculiar walking
      in the hind limbs, not associated with signs of ataxia or hyperkinesia.

PMID- 9026403
TI  - Canadian Conference on Dissemination Research Strengthening Health Promotion and
      Disease Prevention. Proceedings. Vancouver, British Columbia, 27-29 March 1995.

PMID- 9026404
TI  - Update on the diagnosis and management of osteomyelitis.
AB  - Osteomyelitis can be classified by duration, pathogenesis, location, extent, and
      host status. Bone infections are currently classified by the Waldvogel or the
      Cierny-Mader classification. Because the Waldvogel classification is an etiologic
      system and the Cierny-Mader classification is descriptive, both classifications
      can be simultaneously used. The Cierny-Mader classification is based on the
      anatomy of the bone infection and the physiology of the host. Cierny-Mader
      staging allows stratification of long bone osteomyelitis and the development of
      comprehensive treatment guidelines for each stage. Current trends in long bone
      osteomyelitis therapy emphasize early diagnosis and aggressive treatment.
      Radiographs and bone cultures are the mainstays of diagnosis. Imaging with
      radionuclide scans, computerized tomography, and magnetic resonance imaging are
      used when the diagnosis of osteomyelitis is equivocal or to help guage the extent
      bone and soft tissue infection. Surgical treatment involves debridement of
      necrotic bone and tissue, obtaining appropriate cultures, managing dead space,
      and, when necessary, obtaining bone stability. Medical therapy includes improving
      any host deficiencies, initial antibiotic selection, and antibiotic modification
      based on culture results. Antibiotic delivery has expanded to include effective
      oral agents and local therapy with antibiotics mixed in polymethylmethacrylate.
      Cierny-Mader staging was developed to describe long bone osteomyelitis. This
      staging system has to be modified to describe diabetic foot osteomyelitis and
      vertebral osteomyelitis. Osteomyelitis in patients with diabetes mellitus
      involves the bones of the feet or ankles. The vascular and neurologic status of
      the patient must be carefully accessed. Patients may be managed with local
      debridement surgery or ablative surgery plus 2 to 4 weeks of antibiotic therapy
      depending on whether all of the osteomyelitis is surgically removed. If the
      patient does not wish surgery or is not a surgical candidate, suppressive
      antibiotic therapy can be used. Vertebral osteomyelitis is usually hematogenous
      in origin. The diagnosis is made by bone cultures, histology, and radiographs.
      Magnetic resonance imaging and technetium scans are useful in making the
      diagnosis and in gauging the extent of the bone and soft tissue infection.
      Therapy requires parenteral antibiotic therapy and may include early surgery and
      stabilization. The choice of an antibiotic therapy is guided by the bone biopsy
      or debridement culture results.

PMID- 9026406
TI  - HTLV-I/HTLV-II-a model for virus associated neurodegenerative diseases.

PMID- 9026405
TI  - [Processing of contextual syntactic information in a decision making task in
      schizophrenic subjects].
AB  - OBJECTIVE: This research report studies how schizophrenic subjects process
      contextual syntactic information using a double-decision lexical task (deciding
      whether or not strings of letters form French words). Given the automatic nature
      of syntax, we are assuming the preservation of syntactical information processing
      in all the schizophrenic subjects, including those presenting thought disorder
      (TFP), which we name schizophrenic TPF+. METHOD: Twenty control subjects and 20
      schizophrenic subjects (including 10 TFP+ schizophrenic subjects) participated in
      a double-decision lexical task containing syntactic errors. RESULTS: The results
      confirm our hypothesis because we show that all subjects (control and
      schizophrenic) are hampered in recognizing words when they contain grammatical
      errors. CONCLUSIONS: The results contrast with data on the processing of
      contextual semantic information by schizophrenic subjects, since the data in the
      literature conclude that there is an information-processing anomaly on the part
      of these patients. As a result, our study refutes the hypothesis of a generalized
      difficulty in the processing context by schizophrenic subjects.

PMID- 9026407
TI  - XI Migraine Trust International Symposium. London, United Kingdom, 9-12 September
      1996. Abstracts.

PMID- 9026408
TI  - Current readings in nuclear medicine.

PMID- 9026409
TI  - Current reading in nuclear medicine.

PMID- 9026410
TI  - Efficacy of protective creams and/or gels.

PMID- 9026411
TI  - [Professor Franciszek Raszeja--a centenary of his birthday].
AB  - The authors present a concise biography of professor Franciszek Raszeja on the
      centenary of his birthday. Special attention is given to his scientific and
      organizational achievements, particularly in regard to the formation of the
      Orthopaedic Department at the University of Poznan.

PMID- 9026412
TI  - [Arthroscopy of the elbow joint].
AB  - A series of 31 patients who had elbow arthroscopy has been reviewed. Good results
      have been achieved after removal of loose bodies or post-traumatic hematoma. A
      danger of injury to periarticular structures due to the use of arthroscopic
      instruments, especially with pathologically decreased joint volume has been
      pointed out.

PMID- 9026413
TI  - [Early results of vertebral body fracture reduction with the Watson-Jones method
      in personal material].
AB  - Early results of vertebral body fracture reduced with Watson-Jones method in 31
      cases have been presented. After the reduction the height and shape of the
      vertebrae has improved. Delayed treatment rendered the worst results. The mean
      degree of reduction in material analyzed was 61%.

PMID- 9026414
TI  - [Syringomyelia in orthopedic practice].
AB  - Three females with syringomyelia and atrophic shoulder arthropathy, in one
      patient associated also with hypertrophic elbow arthropathy and Morvan syndrome
      have been presented. Despite long duration and apparent symptoms the condition
      has been diagnosed only during hospitalization.

PMID- 9026415
TI  - [Dysplasia epiphysealis capitis femoris].
AB  - A description of rare condition in children, dysplasia epiphysealis capitis
      femoris, known in the literature as Meyers dysplasia is presented. Radiographic
      appearance resembles well known Legg-Calve-Perthes disease. Clinical follow-up of
      6 cases, documented radiographically proves incidence of this condition. The
      management and differential diagnosis is offered.

PMID- 9026416
TI  - [Surgical treatment for recurrent dislocation of the patella in children and
      adolescents].
AB  - Over 100 surgical procedures for recurrent patellar dislocation is described in
      the literature. Soft tissue operations being less traumatic are specifically
      indicated in children and adolescents. This paper deals with three of them: Ali
      Krogius, Garlicki-Salamon and Blauth-Schwarz procedure. Material included 31
      patients aged 8-21 years. Thirty-five operation were done: Ali Krogius procedure
      14 times, Garlicki-Salamon 13 times and Blauth-Schwarz procedure in 8 cases. The
      four grade Hall and Michelli scale was used to assess the results. Excellent
      results were achieved in 12 cases, good in 19, fair in 4 and 2 were poor. Blauth
      Schwarz procedure rendered the best results, the worst were accomplished with Ali
      Krogius operation.

PMID- 9026417
TI  - [Early results of total knee arthroplasty using the GSB endoprosthesis].
AB  - Early results of 20 GSB total knee arthroplasties in 18 patients are presented.
      Twelve patients had rheumatoid arthritis and 8 suffered from gonarthrosis. Good
      results were achieved in 18 knees, one knee was rated satisfactory and one poor.

PMID- 9026418
TI  - [Treatment of tibial shaft fracture by Ender's closed intramedullary nailing].
AB  - Operative technique and results of treatment of tibial shaft fracture using Ender
      nails in 46 patients are presented. In all cases tibial shaft fracture was
      concomitant with massive soft tissue injury and in 18 cases the fracture was
      open. The fracture healed in all cases, bone infection occurred in one patient.

PMID- 9026419
TI  - [Reproducibility of densitometric examinations of the tibial shaft].
AB  - The aim of this paper is to evaluate the reproducibility of tibial shaft
      densitometry in own method under development. It will be expressed as percentage
      value of coefficient of variability (%CV). Bone mineral content (BMC) and bone
      mineral density (BMD) were measured with a dual energy X-ray densitometer Lunar
      DPX; the data were analyzed with a "Orthopedic" software. Three tibial bone scans
      were done in 10 males. High reproducibility was found, ranging from 0.98% to
      1.45% and from 1.45% to 2.08% for BMC and BMD respectively. Reproducibility
      increases as the analyzed surface increases. Reproducibility so high allows for
      further investigations; it might be interesting to monitor BMC and BMD of the
      tibia in course of fracture treatment by Polfix or Zespol method.

PMID- 9026420
TI  - [Early results of treatment for a comminuted articular fracture of the calcaneus
      using a "DERO" fixator].
AB  - The method of treatment for comminuted articular fracture of the calcaneus with
      the use of a "Deroo" fixator is presented. A "Deroo" eliminates the need for the
      cast, allows for an early active foot mobilization in the first post-operative
      day, prevents muscular atrophy. Crosby and Fitzgibbons classification served to
      assess clinical and radiological results; in 5 cases they were rated excellent,
      in 10 good, in 5 fair and in 7 cases results were poor.

PMID- 9026421
TI  - [The role of locally synthesized growth factors and cytokines in pathogenesis of
      osteoporosis].
AB  - Bone remodelling is a complex process involving a number of cellular functions
      directed toward the coordinated resorption and formation of new bone. Bone
      remodelling is regulated by systemic hormones and by local factors. The local
      factors are synthetized by skeletal cells and include growth factors and
      cytokines. The end product of remodeling is the maintenance of a mineralized bone
      matrix, and the major organic component is the collagen. Local factors play an
      important role in pathophysiology of osteoporosis as systemic hormones.

PMID- 9026422
TI  - [Inflammation theory for etiopathogenesis of algodystrophy].
AB  - Algodystrophy (reflex sympathetic dystrophy, Sudeckls atrophy) is the condition
      of still unclear pathogenesis. Paul Sudeck, who described the syndrome was
      convinced of its inflammatory nature; later research established the inducing
      role of the sympathetic nervous system for many years. This view has been
      questioned in the last decade. This paper presents some evidence of inflammatory
      explanation of the disorder: increased uptake of the immunoglobulin IgM labeled
      In111 in affected area, followed by increased vascular permeability for
      macromolecules, and impaired metabolism of the high energy phosphates following
      the impaired oxygen extraction in the affected extremity. Free oxygen and
      hydroxyl radicals injurious role in the course of algodystrophy is also
      established by beneficial treatment with the use of free radicals scavengers
      (mannitol, dimethyl sulfoxide, N-acetylcysteine) and by pathologic
      ultrastructural changes in muscle cells due to oxidative stress. The view of the
      inflammatory nature of acute stage of algodystrophy does not preclude a role of
      sympathetic nervous system but it better explains some clinical aspects of this
      phase of the condition and increases recognition of its complicated nature.

PMID- 9026423
TI  - [Personal modification of the Molskich apparatus for treatment bone loss from
      segment transposition].
AB  - A modified Molskich apparatus has been presented. It enables bone loss treatment
      in a manner similar to the Ilizarov method. A case of patient with 4 cm bone
      defect within tibia treated successfully is presented.

PMID- 9026424
TI  - [Epidermal nevus syndrome--bi-symptom type].
AB  - Epidermal nevus syndrome is a neurocutaneous disorder in which epidermal nevi are
      associated with other abnormalities, mostly of skeletal and central nervous
      system. A case of 6-year old girl with noninflammatory verrucous nevus, skeletal
      abnormalities of the left leg and Wilms tumor is presented.

PMID- 9026426
TI  - 4th Biennial Ray and Robert Kroc Symposium on Neurology. Frontiers of Myelinating
      Cell Biology. Farmington, Connecticut, August 19-21, 1995. Proceedings and
      abstracts.

PMID- 9026425
TI  - IUPHAR GI section conference: New approaches to pharmacotherapy for hepatic and
      gastrointestinal inflammatory and ulcerative disorders. Sperlonga, Italy,
      September 3-7, 1996. Abstracts.

PMID- 9026427
TI  - Hepatocyte growth factor regulates ovarian theca-interstitial cell
      differentiation and androgen production.
AB  - During ovarian follicle growth, precise regulation of the onset of androgen
      production by ovarian theca-interstitial cells (TIC) is necessary for maintaining
      follicle viability. Thus, temporary suppression of TIC androgen production in
      preantral follicles is the key to promoting follicle development. Evidence
      indicates that this process is coordinated via intraovarian growth factors.
      Hepatocyte growth factor (HGF) can induce granulosa cell (GC) proliferation and
      suppress follicular atresia, indicating a role for HGF in promoting follicle
      growth and viability. To determine whether HGF could reversibly suppress androgen
      production, this study investigated the effect of HGF on TIC differentiation and
      steroid production. Twenty-six-day-old rats were used in all studies. HGF
      messenger RNA (mRNA) expression in TIC and GC was determined by reverse
      transcription-PCR. Agarose gel electrophoresis of the PCR products yielded a
      single band corresponding to the 290-bp HGF product for both TIC and GC. HGF
      expression in cultured TIC and GC was not blocked by gonadotropins or HGF. To
      investigate the effects of HGF on TIC steroidogenesis, TIC were isolated from the
      ovaries of hypophysectomized rats. TIC (3.0 x 10(4) cells/well) were cultured
      with LH (0-3 ng/ml) and/or HGF (0-100 ng/ml) for 48 h, and androsterone levels
      were measured by RIA. HGF did not alter androsterone levels in the absence of LH;
      however, HGF reversibly impaired LH-dependent androsterone production by as much
      as 57% (IC50 = 1.5 +/- 0.01 ng/ml). LH (0.3 ng/ml) stimulated progesterone (P4)
      synthesis by TIC (1201 +/- 190 pg/ml) compared to that by control cells (210 +/-
      30 pg/ml). HGF stimulated basal P4 production, and LH-dependent P4 synthesis was
      augmented 2.6-fold by HGF (ED50 = 0.3 +/- 0.01 ng/ml). The DNA content and cell
      viability in TIC cultures were not affected by HGF. The effect of HGF on
      steroidogenic enzyme gene expression in TIC was also investigated via PCR. HGF
      did not alter the level of basal or LH-induced P450 side-chain cleavage and 3
      beta-hydroxysteroid dehydrogenase mRNAs; however, LH-dependent P45017 alpha
      hydroxylase/C17,20 lyase mRNA content was reduced 4.5 fold in the presence of
      HGF. Thus, HGF is expressed in both TIC and GC obtained from the immature rat
      ovary, suggesting its presence in growing follicles. In TIC, HGF stimulated P4
      synthesis, but impaired androgen production, concurrent with a down-regulatory
      effect on P45017 alpha hydroxylase/C17,20 lyase gene expression. Collectively,
      these results indicate that HGF reversibly impairs LH-stimulated androgen
      production in TIC. Such effects may help promote folliculogenesis.

PMID- 9026428
TI  - A fresh-baked report.

PMID- 9026429
TI  - High-tech has arrived in dentistry.

PMID- 9026430
TI  - Computer systems review.

PMID- 9026431
TI  - UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research
      Training in Human Reproduction: Consultation on the Development of New
      Technologies for Female Sterilization. Geneva, 25-27 July 1994.

PMID- 9026432
TI  - Upper gastrointestinal hemorrhage--comparison of the causes and prognosis in
      primary and secondary bleeders.

PMID- 9026433
TI  - Comparison of magnetic resonance imaging and endoscopy in distinguishing the type
      and severity of inflammatory bowel disease.

PMID- 9026434
TI  - A three-year follow-up of self-expanding metal stents in the endoscopic
      palliation of longterm survivors with malignant biliary obstruction.

PMID- 9026435
TI  - Efficacy and safety of hydrostatic balloon dilatation of ileocolonic Crohn's
      studies: a prospective longterm analysis.

PMID- 9026436
TI  - Comparison of responses of DNA topoisomerase I from Candida albicans and human
      cells to four new agents which stimulate topoisomerase-dependent DNA nicking.
AB  - DNA topoisomerase I is a potential target for therapeutic antifungal agents
      predicted to have a fungicidal mode of action. This report describes four agents
      with varying degrees of selectivity for the fungal topoisomerase I compared to
      the human enzyme: 5-hydroxy-1H-indole-3-acetic acid (5-HIAA), quinizarin, dibenzo
      p-dioxin-2-carboxylic acid and 7-amino-4-hydroxy-2-naphthalenesulfonic acid.
      Taken together with the response of topoisomerase to camptothecin and
      aminocatechol, these data suggest that there are sufficient structural
      differences between the topoisomerase I from Candida albicans and human cells to
      allow selective targeting of the fungal topoisomerase I over its human
      counterpart.

PMID- 9026437
TI  - Identification of the gene encoding DNA topoisomerase I from Candida albicans.
AB  - A gene encoding a type I topoisomerase (TOP1) was isolated from Candida albicans,
      sequenced, and expressed in Saccharomyces cerevisiae. The TOP1 gene was
      identified from a C. albicans genomic library by hybridization with the product
      of a polymerase chain reaction with degenerate primer sets encoding regions
      conserved in other TOP1 genes. A clone containing an open reading frame of 2463
      bp and predicted to encode a protein of 778 amino acids with sequence similarity
      to eukaryotic type I topoisomerases was identified. The C. albicans TOP1 gene
      restored camptothecin sensitivity and increased the topoisomerase activity in S.
      cerevisiae, indicating that the DNA fragment encodes a functional C. albicans
      topoisomerase I.

PMID- 9026438
TI  - Characterization of a XhoI isoschizomer in Streptomyces aureofaciens after
      actinophage infection.
AB  - After infection of tetracycline producing strains of S. aureofaciens with
      actinophages mu 1/6 and B1 some phage resistant colonies were obtained in each
      experiment. These colonies expressed a new restriction-modification (RM) system
      of type II, which was different from the common RM system (SauLPI) of these
      strains recognizing the sequence GCCGGC. This new RM system was not detected
      before in parental strains. The new endonuclease was purified from a phage
      resistant strain of S. aureofaciens B96, using two step column chromatography to
      the grade without non-specific nucleolytic activity. SauLPII endonuclease
      recognized and cleaved the palindromic hexanucleotide sequence 5'-C/TCGAG-3',
      thus it was a true isoschizomer of XhoI.

PMID- 9026439
TI  - Phosphorylation of GroEL, DnaK and other proteins from Thiobacillus ferrooxidans
      grown under different conditions.
AB  - The levels of phosphorylation of the chaperones DnaK and GroEL and other proteins
      varied when cells of Thiobacillus ferrooxidans were subjected to phosphate
      starvation. The phosphorylated amino acid of GroEL was found to be threonine. Our
      results show that not only heat shock, but also a nutrient starvation stress
      leads to phosphorylation of chaperones and, in addition, support the possible
      role of phosphorylation of these proteins in the sensing and regulation of stress
      responses in bacteria.

PMID- 9026440
TI  - Incorporation of choline into Streptococcus pneumoniae cell wall antigens:
      evidence for choline kinase activity.
AB  - The choline-containing teichoic and lipoteichoic acids play an important part in
      cell wall metabolism of Streptococcus pneumoniae. We propose that a choline
      kinase enzyme has a role in the synthesis of these antigens. The presence of this
      enzyme was demonstrated in cell free extracts of S. pneumoniae by measuring the
      fall in ATP concentration due to phosphorylation of choline. Genomic DNA of S.
      pneumoniae hybridised with a probe consisting of an internal fragment of the
      choline kinase gene of Saccharomyces cerevisiae and one consisting of the choline
      binding domain of lytA.

PMID- 9026441
TI  - Purification and biochemical characterization of pullulanase type I from Thermus
      caldophilus GK-24.
AB  - A thermostable pullulanase (pullulan 6-glucanohydrolase, EC 3.2.1.41) has been
      purified to homogeneity from Thermus caldophilus GK-24 by chromatographic
      methods, including gel-filtration and ion-exchange chromatography. The specific
      activity of the enzyme was increased 431-fold with a recovery of 13.2%. The
      purified enzyme was a monomer, M(r) = 65 kDa as estimated by SDS-PAGE and gel
      filtration. The pI was 6.1. The enzyme was most active at pH 5.5. The activity
      was maximal at 75 degrees C and stable up to 95 degrees C for 30 min at pH 5.5.
      The enzyme was stable to incubation from pH 3.5 to pH 8.0 at 4 degrees C for 24
      h. The activity of the enzyme was stimulated by Mn2+ and Mg2+ ions. Ni2+, Ca2+,
      Co2+ ions and EDTA did not inhibit the enzyme activity. The enzyme hydrolyzed the
      alpha-1,6 linkages of amylopectin, glycogens, alpha, beta-limited dextrin, and
      pullulan. The enzyme caused the complete hydrolysis of pullulan to maltotriose.
      The activity was inhibited by alpha-, beta-, or gamma-cyclodextrins. The N
      terminal sequence [(AIa-Pro-Gln-(Asp or Tyr)- Asn-Leu-Leu-Xaa-ILe-Gly-Ala(Ser)]
      showed some similarity to those of bacterial pullulanases.

PMID- 9026442
TI  - Identification of iron superoxide dismutase and a copper/zinc superoxide
      dismutase enzyme activity within the marine cyanobacterium Synechococcus sp. WH
      7803.
AB  - Three constitutive forms of superoxide dismutase activity have been demonstrated
      in the cyanobacterial marine picoplankter Synechococcus sp. WH 7803 using
      polyacrylamide gel activity staining techniques. A protein which gave a positive
      non-haem iron stain on native polyacrylamide gels exhibited N-terminal similarity
      to both the iron superoxide dismutase and the manganese superoxide dismutase of
      Escherichia coli. The metal prosthetic group of each of the three activity bands
      was characterised by analysing their differential sensitivities to 5 mM H2O2, 2
      mM cyanide and 2 mM of the copper chelator diethyldithiocarbamate. Three distinct
      superoxide dismutase activities were observed, an iron superoxide dismutase, a
      copper/zinc superoxide dismutase and a third form which has not been identified.
      Growth of Synechococcus cells in ASW medium containing no added iron resulted in
      no alteration in the activity of the iron superoxide dismutase. Growth of
      cultures in the absence of copper or zinc resulted in differential changes in the
      activities of the copper/zinc superoxide dismutase and the unidentified
      superoxide dismutase.

PMID- 9026443
TI  - Polymerase chain reaction and an outer membrane protein gene probe for the
      detection of Porphyromonas gingivalis.
AB  - A sensitivity assay for Porphyromonas gingivalis based upon the polymerase chain
      reaction (PCR) was developed. A 426-bp sequence, including a DraI-HincII DNA
      fragment (278 bp) encoding the 40-kDa outer membrane protein of the P. gingivalis
      gene was amplified. PCR products were obtained from chromosomal DNAs of the P.
      gingivalis strains tested but not from those of other oral microorganisms. The
      lower limit of template DNA detection was 10 pg with 30 cycles and 100 fg with 40
      cycles of PCR by agarose gel electrophoresis. The PCR products were hybridized
      with DraI-HincII DNA fragment internal to the PCR primers regions used. The lower
      limit of hybridization detection was 10 pg and 10 fg of template DNA with 30 and
      40 cycles of PCR, respectively. These results demonstrated the simplicity,
      rapidity and specificity of the procedure, as well as the use of the DraI-HincII
      DNA fragment in the identification of P. gingivalis.

PMID- 9026444
TI  - The Escherichia coli K99 periplasmic chaperone FanE is a monomeric protein.
AB  - The monomeric or dimeric nature of the K99 periplasmic chaperone FanE was
      examined. The gene encoding FanE was subcloned in a pINIIIA1 derivative
      expression vector. A complementation experiment showed that the subcloned FanE
      was biologically functional. The protein was purified from the periplasm of cells
      harbouring the constructed plasmid. Automated Edman degradation experiments
      confirmed the predicted N-terminal amino acid sequence of FanE. A polyclonal
      mouse antiserum was raised against the FanE chaperone. The monomeric or
      oligomeric nature of the protein in the periplasm was studied by gel filtration,
      immunoblotting and chemical cross-linking experiments. The results indicated that
      FanE is a monomeric protein, in contrast to the K88 periplasmic chaperone.

PMID- 9026445
TI  - Detection of the single-stranded DNA of Streptomyces plasmid pSA1.1 and a binding
      histone-like protein.
AB  - Streptomyces plasmid pSA1.1 accumulated single-stranded DNA as replication
      intermediates in S. lividans; therefore, this plasmid was considered to replicate
      by a rolling-circle mechanism. A DNA-binding protein (pI > 9.7 and about 10 kDa)
      was purified on a denatured DNA-Cellulose column, then on a native DNA-Cellulose
      column. The N-terminal amino acid sequence of this protein has a high homology
      with bacterial histone-like proteins. In the gel retardation assay, this protein
      bound with the single-stranded DNA of pSA1.1. We propose that this protein may
      participate in the replication of pSA1.1.

PMID- 9026446
TI  - Is the CvaA protein, encoded within the colicin V export gene cvaA, required for
      colicin V transport?
AB  - The antibacterial peptide toxin colicin V is exported from Escherichia coli cells
      by a signal sequence-independent, ABC export system. Export requires at least
      three proteins-membrane fusion protein CvaA, ABC export protein CvaB, and outer
      membrane protein TolC. The cvaA gene also encodes a second protein, CvaA,
      initiated from an in-frame translational re-start within the cvaA coding
      sequence. To determine whether the internally encoded CvaA protein also functions
      in the export pathway, the putative start codons for CvaA were mutagenized, while
      maintaining CvaA function. Elimination of CvaA translation caused no change in
      colicin V export levels, indicating that the CvaA protein is not required in the
      secretion pathway.

PMID- 9026447
TI  - 1-Aminocyclopropane-1-carboxylate deaminase genes from Pseudomonas strains.
AB  - Microbial ACC deaminase catalyses the conversion of 1-aminocyclopropane-1
      carboxylate (ACC), the precursor to the phytohormone ethylene, to ammonia and
      alpha-ketobutyrate. We screened microorganisms for ACC degrading ability and
      cloned and sequenced the ACC deaminase genes from two Pseudomonas strains which
      displayed high enzyme activity. One of the genes was homologous with two
      previously sequenced ACC deaminase genes, but the other was different.

PMID- 9026448
TI  - Leptospira interrogans and Leptospira peptidoglycans induce the release of tumor
      necrosis factor alpha from human monocytes.
AB  - Elevated plasma concentrations of the cytokine tumor necrosis factor alpha (TNF
      alpha) have been observed in patients affected by leptospirosis. In this study we
      found that a preparation of peptidoglycan of Leptospira interrogans, serovar
      copenhageni, was able to induce the release of TNF alpha from peripheral blood
      mononuclear cells. TNF alpha induction occurred in a dose dependent manner and
      was not affected by the endotoxin inhibitor polymixin B. This is the first report
      on induction of TNF alpha release by a peptidoglycan of spirochetes. Our findings
      are consistent with existing clinical data and provide a potential mechanism for
      TNF alpha production.

PMID- 9026449
TI  - Immunolocalization of a 22 kDa protein (IPLA7, P22) of Borrelia burgdorferi.
AB  - The monoclonal antibody LA7 was raised against the species-specific Borrelia
      burgdorferi lipoprotein P22 (= IPLA7), which induces antibody formation in
      patients with Lyme arthritis. It is composed of 194 amino acids with a calculated
      molecular mass of 21.8 kDa. Its gene on the linear chromosome is 582 nucleotides
      in length. The aim of this study was to localize the protein P22 by immune
      electron microscopy. Immunolabeling of Borrelia burgdorferi with LA7 and an anti
      mouse immunogold conjugate proved that P22 is an outer membrane protein. This
      finding was confirmed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis of the outer envelope fraction, which contained 99% of the P22
      proteins.

PMID- 9026450
TI  - Phase I and phase II enzymes produced by Cunninghamella elegans for the
      metabolism of xenobiotics.
AB  - The filamentous fungus Cunninghamella elegans has the ability to metabolize
      xenobiotics, including polycyclic aromatic hydrocarbons and pharmaceutical drugs,
      by both phase I and II biotransformations. Cytosolic and microsomal fractions
      were assayed for activities of cytochrome P450 monooxygenase, aryl
      sulfotransferase, glutathione S-transferase, UDP-glucurono-syltransferase, UDP
      glucosyltransferase, and N-acetyltransferase. The cytosolic preparations
      contained activities of an aryl sulfotransferase (15.0 nmol min-1 mg-1), UDP
      glucosyltransferase (0.27 nmol min-1 mg-1) and glutathione S-transferase (20.8
      nmol min-1 mg-1). In contrast, the microsomal preparations contained cytochrome
      P450 monooxygenase activities for aromatic hydroxylation (0.15 nmol min-1 mg-1)
      and N-demethylation (0.17 nmol min-1 mg-1) of cyclobenzaprine. UDP
      glucuronosyltransferase activity was detected in both the cytosol (0.09 nmol min
      1 mg-1) and the microsomes (0.13 nmol min-1 mg-1). N-Acetyltransferase was not
      detected. The results from these experiments provide enzymatic mechanism data to
      support earlier studies and further indicate that C. elegans has a broad
      physiological versatility in the metabolism of xenobiotics.

PMID- 9026451
TI  - Phenotypic expression of a mannose-sensitive hemagglutinin by a Vibrio cholerae
      O1 E1Tor strain and evaluation of its role in intestinal adherence and
      colonization.
AB  - A Vibrio cholerae O1 strain (1150) of the EIT or biotype and Ogawa serotype with
      haemagglutination (HA) activity was subjected to TnphoA mutagenesis. Out of
      several mutants isolated, one HA- and another HA+ mutant were further
      characterised. The HA- mutant showed about 50% reduction in its intestinal
      adherence capacity in vitro and about 9-fold decrease of its colonisation ability
      in vivo, as compared to the wild-type strain. Subsequent studies showed that the
      HA activity of strain 1150 was mediated by a mannose-sensitive haemagglutinin
      (MSHA). Thus, the phenotypic expression of MSHA appears to be partly responsible
      for the intestinal adherence and colonisation properties of strain 1150.

PMID- 9026452
TI  - Electrotransformation of lactobacillus acidophilus group A1.
AB  - Two strains of Lactobacillus acidophilus Group A1, the neotype ATCC 4356 and a
      human isolate NCFM-N2, widely used as a dietary adjunct in milk and cultured
      dairy products, were transformed with plasmid DNA by electroporation. The
      transformation characteristics exhibited by the two L acidophilus strains were
      found to differ markedly even though they appeared similar at the genomic level
      based on the DNA patterns of SmaI restriction fragments. To our knowledge, this
      is the first report of a consistent, reproducible transformation system of
      Lactobacillus acidophilus strains comprising the A1 DNA homology group.

PMID- 9026453
TI  - Development of a polymerase chain reaction/restriction fragment length
      polymorphism method for Saccharomyces cerevisiae and Saccharomyces bayanus
      identification in enology.
AB  - Several yeast strains of the species Saccharomyces cerevisiae, S. bayanus and S.
      paradoxus, first identified by hybridization experiments and measurements of
      DNA/DNA homology, were characterized using polymerase chain reaction/restriction
      fragment length polymorphism (PCR/RFLP) analysis of the MET2 gene. There was no
      exception to the agreement between this method and classical genetic analyses for
      any of the strains examined, so PCR/RFLP of the MET2 gene is a reliable and fast
      technique for delimiting S. cerevisiae and S. bayanus. Enological strains
      classified as S. bayanus, S. chevalieri, and S. capensis gave S. cerevisiae
      restriction patterns, whereas most S. uvarum strains belong to S. bayanus.
      Enologists should no longer use the name of S. bayanus for S. cerevisiae Gal
      strains, and should consider S. bayanus as a distinct species.

PMID- 9026454
TI  - The rpoD gene functions as a multicopy suppressor for mutations in the
      chaperones, CbpA, DnaJ and DnaK, in Escherichia coli.
AB  - The CbpA protein is an analog of the DnaJ molecular chaperone of Escherichia
      coli. The dnaJ- cbpA- double-null mutant exhibits severe defects in cell growth,
      namely, a very narrow temperature range for growth. To gain insight into the
      functions of CbpA as well as DnaJ, we isolated a multicopy suppressor gene that
      permits this dnaJ- cbpA- mutant to grow normally at low temperatures. The
      suppressor gene was identified as rpoD, the gene that encodes the major sigma 70.
      The biological implications of this finding are examined and discussed.

PMID- 9026455
TI  - The putative immunity protein of the gram-positive bacteria Leuconostoc
      mesenteroides is preferentially located in the cytoplasm compartment.
AB  - Immunity proteins are though to protect bacteriocin-producing bacterial strains
      against the bactericidal effects of their own bacteriocin. The immunity protein
      which protects the lactic acid bacterium Leuconostoc mesenteroides against
      mesentericin Y105(37) bacteriocin was detected and localized by
      immunofluorescence and electron microscopy, using antibodies directed against the
      C-terminal end of the predicted immunity protein. The antibodies recognized the
      immunity proteins of various strains of Leuconostoc, including Leuconostoc
      mesenteroides and Leuconostoc gelidum. This study demonstrated that immunity
      proteins produced by Leuconostoc mesenteroides accumulated in the cytoplasmic
      compartment of the bacteria. This is in contrast with other known immunity
      proteins, such as the colicin immunity proteins, which are integral membrane
      proteins possessing three to four transmembrane domains.

PMID- 9026456
TI  - Cyclic AMP-independent catabolite repression in bacteria.
AB  - Until recently, only one mechanism of catabolite repression in bacteria, a
      mechanism dependent on the cyclic AMP receptor protein of Escherichia coli, was
      understood in molecular detail. Two cyclic AMP-independent catabolite repression
      mechanisms are currently under study. One such mechanism, found in E. coli,
      involves the catabolite repressor/activator (Cra) protein (formerly designated
      the fructose repressor FruR) which represses sugar catabolic systems and
      activates sugar anabolic systems. When catabolites bind to Cra, Cra dissociates
      from the DNA causing catabolite activation and catabolite repression,
      respectively. The second such mechanism, found in Bacillus subtilis, involves a
      catabolite-activated, ATP-dependent protein kinase that phosphorylates a specific
      seryl residue in the small phosphocarrier protein, HPr, of the phosphotransferase
      system. HPr(ser-P) binds to a transcription factor, CcpA, to promote DNA binding.
      DNA binding of the complex in turn promotes catabolite repression or catabolite
      activation, depending on the target operon. The characterization of these novel
      mechanisms establishes that cyclic AMP-independent catabolite control is
      operative in bacteria, and that multiple mechanisms of catabolite control evolved
      independently of each other.

PMID- 9026457
TI  - [Attenuation of bacteriophage phi80 repression].
AB  - Data are obtained suggesting the involvement of the cor gene of the [symbol: see
      text] 80 phage in regulation of phage operons. Mutations in the cor gene, which
      is located outside the region of phage [symbol: see text] 80 immunity, cause
      disturbances in the establishment and maintenance of the phage lysogenic state.
      The cor gene was shown to affect RecA-inactivation of the phage repressor induced
      by UV-irradiation. A model suggesting cor gene involvement in [symbol: see text]
      80 operon regulation is discussed.

PMID- 9026458
TI  - [Phenotypic expression of the Ca2+-dependence trait in recombinant cells of
      Yersinia pestis (Lehmann, Neumann)].
AB  - A conceptual model of the Yersinia pestis Ca(2+)-dependence mechanism is
      proposed. The model is based on data from analyses of peculiarities of
      recombinant cells of this plague-causing agent carrying the cloned first Bg/II
      fragment of the Ca(2+)-dependence plasmid (pCaD) and a combination of this
      fragment and other plasmid pCaD fragments. The data obtained also allowed a
      revision of the role of the lcr GVH locus of pCaD in this phenomenon.

PMID- 9026459
TI  - [Identification of genes controlling the transition of Salmonella typhimurium
      bacteria to a non-culturable state].
AB  - Mutants of Salmonella typhimurium with an impaired process of transition to the
      nonculturable state were tainted. Mutants were divided into four phenotypic
      groups. In four mutants (representatives of each phenotypic group), genes with
      TnPhoA transposon insertions were cloned; these insertions caused a disturbance
      in the process of mutant cell transition to the nonculturable state. Nucleotide
      sequences of mutant gene fragments were determined. Comparison of nucleotide
      sequences obtained with a data bank on DNA nucleotide sequences of
      enterobacterial genomes allowed the identification of four genes involved in the
      control of nonculturable form generation in salmonellae.

PMID- 9026460
TI  - [Role of juvenile hormone metabolism in the adaptation of Drosophila populations
      to stressful environmental conditions].
AB  - The effect of heat stress on the system of degradation of juvenile hormone (JH)
      and on fertility of Drosophila virilis and D. melanogaster was studied. In wild
      type strains of both species, stress resulted in delay of oviposition and in a
      decrease in JH hydrolysis and fertility, which lasted for several days after heat
      treatment. Experimental repression of juvenile hormone esterase showed that
      stress response of the Drosophila reproductive system is determined by the
      decrease in JH hydrolysis. Fertility of Drosophila strains that did not respond
      to stress by decreasing JH degradation level was not reduced under stress. The
      role of JH metabolism in Drosophila reproduction under stress and in adaptation
      of natural Drosophila populations to stressful environments is discussed.

PMID- 9026461
TI  - [Cytogenetic and phenotypic variation in central and peripheral populations of
      the malaria mosquito, Anopheles messeae Fall. (Diptera, Culicidae)].
AB  - Chromosome polymorphism and morphological variation in malaria mosquito Anopheles
      messeae larvae of populations from western Siberia, Kyrgyzstan, and southern
      Kazakhstan were studied. It is shown that the level of inversion polymorphism
      decreases at the boundary of the range. A shift in the phenotypic norm observed
      in the peripheral biotopes is attributed to direct selection larvae with
      "southwestern" chromosomal variants and to modification.

PMID- 9026462
TI  - [Properties of inbred Drosophila melanogaster lines obtained from a population
      selected for an increased rate of embryonic development].
AB  - Two heterogeneous Drosophila melanogaster populations were subjected to selection
      for an increased rate of embryonic development by picking out the first 10% of
      hatching larvae. After repeating this procedure in 15 generations, "fast"
      populations were obtained, in which the duration of embryonic development at high
      temperature (31-32 degrees C) was 30-40 min less than in nonselected control
      populations. The results of preliminary experiments on substituting the second
      and third chromosomes in the selected and control populations provide evidence
      that selected genes responsible for accelerated development are located on the
      second chromosome. Inbreeding in 12 generations of selected populations was used
      to obtain about 40 lines homozygous, in particular, at the alcohol dehydrogenase
      gene. In four lines, the developmental rate was higher than in a homozygous
      control line, but others did not differ from control or developed more slowly.
      The duration of embryonic development at 32 degrees C in fast lines was 50-70 min
      shorter than in control, but this difference was significantly less at lower
      temperatures (25 and 17 degrees C). Hence, high temperature is primarily a factor
      in providing conditions for the expression of genes determining the developmental
      rate, rather than a factor of selection for these genes. It is suggested that
      selected genes modify developmental rate dependence on temperature.

PMID- 9026463
TI  - [Mutagenicity of drinking water in various districts of Moscow].
AB  - The mutagenicity of the drinking water from 16 districts of Moscow was
      investigated by analyzing of chromosome aberrations induced in cells of Crepis
      capilaris seeds used as a plant test system. Cytogenetic analysis revealed
      mutagenic activity in drinking water samples from four administrative regions,
      namely the Biryulevo-Zapadnoe district of Southern region (2.4%), Obruchevskii
      district of the Southwestern region (1.61%), Severnoe Tushino district of the
      Northwestern region (1.45%), and Perovo district of the Western region (1.18%).
      The frequency of chromosome aberrations found was significantly higher than in
      the spontaneous control (0.37%). Mutagenic activity was not detected in water
      samples taken from the Moscow oblast and from four open reservoirs.

PMID- 9026464
TI  - [Variability of satellite DNA II and IV in cattle, various representatives of the
      subfamily Bovinae and their hybrids].
AB  - Polymorphism of satellite DNA II and IV was studied in Bos taurus by means of
      Southern blotting and dot hybridization. Of primary interest is the absence of
      restriction fragment length polymorphism at the individual and interbreed levels.
      Differences in the content of satellite II in the genome are demonstrated for
      animals of the Kholmogorskaya and Yakutian breeds. The specific features of
      satellite IV organization in the bison, banteng and yak are revealed, allowing
      the use of the satellite as a specific genetic marker. Superposition of parental
      organizational types of this class of repeats is detected for the interspecies
      hybrids yak x cattle, banteng x cattle, and bison x cattle. At the same time,
      several cases of deviation from classic inheritance of such parental types in the
      interspecies hybrids were found.

PMID- 9026465
TI  - Frequency distribution of HLA-antigens, genes and haplotypes in the migrant
      population of Magadan as a function of length of residence in the region.
AB  - Peculiarities of the frequency distribution of antigens, genes, and haplotypes at
      subloci A, B, and Cw of the HLA system in 1429 Slavic inhabitants of Magadan are
      presented in dependence on length of residence in extreme conditions. No
      significant differences were revealed with respect to frequency of genes and
      antigens in inhabitants with different lengths of residence in northeastern
      Russian conditions. Analysis of gamete associations shows that the revealed
      positive or negative associativity in some cases is characteristic for Caucasoids
      on the whole, but an associativity specific to inhabitants of Magadan was also
      established. Its character depends on the length of residence in extreme
      conditions.

PMID- 9026466
TI  - [Genetic structure of the Mari population and its genetic position in the system
      of other Finno-Ugrian population groups].
AB  - The genetic structure of the Mari population was studied by genetic markers (ABO,
      TF, GC, PI, HP, ACP1, PGM1). Nei's GST statistic was 0.0192, showing that 1.92%
      of the genetic diversity in the Mari population can be attributed to the
      subdivision effect. Genetic distances between Maris and other Finno-Ugric groups
      were estimated.

PMID- 9026467
TI  - [Genotoxic effect of formaldehyde in somatic human cells in vivo].
AB  - The genotoxic effect of formaldehyde (F) (chromosome aberrations in peripheral
      blood lymphocytes, micronucleated cells in buccal mucosa) was studied in workers
      manufacturing nitrogen fertilizer and exposed to F at concentrations exceeding
      maximum permissible ones for a working area (group 1); in workers at the
      Department of Normal Anatomy who handle moist anatomical preparations (group 2);
      and in students who attended anatomy lessons once (group 3). A pronounced F
      cytotoxic effect was found in groups 1 and 2. In lymphocytes obtained from
      individuals of group 1, in which frequency of chromosome aberrations exceeded the
      control level fourfold, metaphase plates were revealed only after 72 h of
      cultivation. A similar reduction of the statmokinetic index and an increase in
      chromosomal aberrations were observed after in vitro F treatment of lymphocytes.
      In groups 2 and 3, a four- to fivefold excess of micronucleated cells was found
      in buccal mucosa. In students, the number of micronucleated cells remained higher
      both 24 and 48 h after they handled moist formaline preparations in anatomy class
      for 40 min.

PMID- 9026468
TI  - [Mobile elements of the Drosophila genome as a marker of crossing over in
      isogenic crosses with a balancer strain].
AB  - The ability of the Cy/Pm; D/Sb balancer strain to inhibit crossing over in
      isogenic crosses was studied. Regions of interchromosomal exchange were detected
      within and outside the inverted regions with the help of the MDG1, Dm412, copia,
      and B104 mobile elements. Certification of mobile element distribution patterns
      in balancer strains was proposed. Crossing over was suggested as a possible
      reason for the polymorphism of daughter strains and as useful for estimating
      frequency of transposition of mobile elements in similar interstrain crosses.

PMID- 9026469
TI  - [Analysis of the interaction of genotypic and paratypic factors in the
      development of maxillo-dental anomalies in ontogeny].
AB  - Component analysis of total phenotypic variance was used to analyze data on 80
      pairs of twins aged 3 to 18 years, examined in the Stupino outpatient dental
      clinic, Moscow oblast. Genotypic and environmental factors are shown to play
      different roles in the development of abnormalities of teeth, dental arches, and
      occlusion at different ontogenetic periods of deciduous, mixed, and permanent
      dentition. Periods when paratypic factors prevailed were revealed. This made it
      possible to identity periods when prophylaxis and orthodontic treatment are the
      most advisable.

PMID- 9026470
TI  - [Metallonucleoliposome complexes as a vehicle for gene delivery to mouse skeletal
      muscles in vivo].
AB  - A simple new method for preparing plasmid DNA and preformed zwitterionic liposome
      complexes is proposed. The ability of these metallonucleoliposome complexes to
      serve as a vehicle for gene delivery to mammalian cells in vivo was studied. A
      high level of expression of the reporter gene introduced was observed in mouse
      skeletal muscles in vivo.

PMID- 9026471
TI  - [The meadow Mari: inbreeding and endogamy].
AB  - The genetic structure of Lugovye Maris was studied on the basis of marital
      migration. Malecot's parameters of isolation and endogamy index were estimated in
      four rations of the Marii El Republic, which is populated by Maris. High values
      of the endogamy index (0.80 and 0.88) never observed previously in any Russian
      populations, were revealed in two rations. The lack of significant correlation
      between endogamy and local inbreeding was analyzed. A significant correlation
      (0.70) between endogamy and effective population size was revealed.

PMID- 9026473
TI  - Regulation of metal absorption in the gastrointestinal tract.

PMID- 9026472
TI  - Gastric surfactant and the hydrophobic mucosal barrier.

PMID- 9026474
TI  - Prevalence of Helicobacter pylori infection and related gastroduodenal lesions in
      spouses of Helicobacter pylori positive patients with duodenal ulcer.
AB  - BACKGROUND: To date, very few studies have evaluated the risk of infection among
      spouses of Helicobacter pylori positive patients and their results are
      conflicting. AIM: To assess the seroprevalence of H pylori infection in spouse of
      H pylori positive patients with duodenal ulcer as compared with age and sex
      matched volunteer blood donors, as well as the frequency of endoscopic
      gastroduodenal lesions in these spouses, according to the presence or absence of
      gastrointestinal complaints. METHODS: Some 124 spouses (48% males) of patients
      with duodenal ulcer consecutively seen over a 10 month period were studied. They
      were all screened for serum IgG anti-H pylori antibodies and asked to complete a
      questionnaire with particular reference to the presence of chronic or recurrent
      dyspepsia. Upper gastrointestinal tract endoscopy with antral and corpus biopsy
      specimens taken for histological examination and urease rapid test was offered to
      all seropositive spouses. Volunteer blood donors (248), living in Milan and
      matched for age, sex, north-south origins, and socioeconomic status to the cases,
      were used as controls. RESULTS: Spouses of patients with duodenal ulcer had a
      significantly higher seroprevalence of H pylori infection than controls (71% v
      58%, p < 0.05); 30 of 88 (34%) H pylori positive spouses complained of dyspeptic
      symptoms compared with only four of 34 (12%) seronegative spouses (p < 0.02). At
      endoscopy, H pylori infection was confirmed in 48 of 49 (98%) seropositive
      spouses. The endoscopic findings in those spouses showed active duodenal ulcer in
      eight (17%), duodenal scar and cap deformity in two (4%), active gastric ulcer in
      two (4%), erosive duodenitis in three (6%), antral erosions in two (4%), antral
      erosions plus duodenitis in one, and peptic oesophagitis in another patient. The
      prevalence of major endoscopic lesions was significantly higher in symptomatic
      spouses than in those who had never been symptomatic. CONCLUSIONS: These findings
      show that being the spouse of an H pylori positive patient with duodenal ulcer
      may increase the risk of H pylori colonisation and perhaps of peptic ulcer
      disease, and raises questions as to whether serological screening of cohabiting
      partners of H pylori positive patients with duodenal ulcer may be indicated.

PMID- 9026475
TI  - Helicobacter pylori infection in spouses of patients with duodenal ulcers and
      comparison of ribosomal RNA gene patterns.
AB  - BACKGROUND: In recent studies, familial coinfection with the same Helicobacter
      pylori strains has been indicated, but more data are necessary to confirm intra
      familial spread of the micro-organism. AIMS: The aim of this study was (a) to
      assess the frequency of H pylori infection in spouses of patients with duodenal
      ulcers and (b) to investigate the possibility of intraspousal typing of the
      respective strains. PATIENTS: Sixty four patients with duodenal ulcer and their
      spouses were included in the study. METHODS: The H pylori infection was confirmed
      after endoscopy by culture and histological examination of biopsy specimens, and
      CLO test. The isolates were compared on the basis of their rRNA gene patterns
      (ribopatterns) after digestion of chromosomal DNA by the restriction
      endonucleases HaeIII or HindIII. RESULTS: Of the patients, 54 were found to be H
      pylori positive. Of the respective spouses, 42 (78%) were also H pylori positive.
      In contrast, only two out of 10 (20%) partners of H pylori negative patients were
      infected. Ribopatterns of H pylori strains derived from 18 patients and their
      spouses showed that in each of eight couples a single strain had colonised both
      partners, while in the remaining 10 couples each partner was colonised by a
      distinct H pylori strain. CONCLUSIONS: These data suggest person to person
      transmission within couples or exposure to a common source of infection.

PMID- 9026476
TI  - Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori
      infected mice are host dependent and separate from antral gastritis.
AB  - BACKGROUND/AIMS: The role of host factors has been neglected in studies of the
      pathogenesis of Helicobacter associated disease. The aim of this study was to
      assess the response of different mouse strains to infection with a single strain
      of Helicobacter felis. METHOD: Six strains of inbred mice were infected with the
      identical H felis culture and were killed at one month, two months, and six
      months after infection to assess histopathological changes. In addition, two
      strains of mice were infected with a mouse adapted strain of H pylori and
      examined at six months after infection. RESULTS: In SJL, C3H/He, DBA/2, and
      C57BL/6 infected mice, severe to moderate chronic active gastritis was observed
      only in the body of the stomach, which increased in severity over time with
      specialised cells in the body glands being replaced. As the severity of this
      damage in the body increased and atrophic changes were seen, the level of
      bacterial colonisation of the antrum decreased. In contrast, in BALB/c and CBA
      mice, there was only mild gastritis in the antrum, no remarkable changes were
      detected in their body mucosa, and no atrophy was seen over time. In both these
      strains of mice, heavy bacterial colonisation was seen, which tended to increase
      over the period of the experiment. Of particular importance in this experiment
      was that bacterial colonisation was mainly restricted to the antrum yet the
      atrophy, when present, was only observed in the body of the stomach. H pylori
      infected C3H/He mice showed moderate colonisation of the antrum, which persisted
      up to six months with little development of atrophy. In contrast, H pylori in
      C57BL/6 mice showed excellent colonisation of the antrum at two months but six
      months after infection there was moderate to severe body atrophy, which was
      associated with a loss of bacteria from the antrum. CONCLUSIONS: These findings
      challenge current concepts of the development of Helicobacter induced atrophy in
      that active chronic gastritis of antrum or the body mucosa, or both, is not a
      prerequisite. They also suggest an autoimmune basis for the pathology although no
      autoantibody or antibody to the H+/K+ ATPase was detected. Loss of infecting
      helicobacters from the stomach together with development of an atrophic gastritis
      in the body of the stomach is similar to the pattern found in certain H pylori
      infected human subjects.

PMID- 9026477
TI  - Marked increase in gastric acid secretory capacity after omeprazole treatment.
AB  - BACKGROUND: In contrast with the histamine2 (H2) blockers, proton pump inhibitors
      have not been shown to give rebound hypersecretion of acid. Taking into
      consideration the hyperplasia of the enterochromaffin-like (ECL) cell provoked by
      hypergastrinaemia secondary to profound acid inhibition and the central role of
      histamine from ECL cells in the regulation of acid secretion, the lack of any
      rebound acid hypersecretion after treatment with proton pump inhibitors has been
      questioned. AIMS: To reassess the effect of treatment with omeprazole on post
      treatment acid secretion. METHODS AND PATIENTS: Basal and pentagastrin stimulated
      acid secretion were determined in nine patients with reflux oesophagitis before
      and 14 days after termination of a 90 day treatment period with the proton pump
      inhibitor omeprazole (40 mg daily). Basal gastrin release were determined before
      and during omeprazole treatment. Furthermore, biopsy samples from the oxyntic
      mucosa were taken before and at the end of the treatment period for chemical
      (histamine and chromogranin A (CgA)) evaluation of the ECL cell mass. RESULTS: A
      substantial increase in meal stimulated gastrin release during omeprazole
      treatment resulted in an increased ECL cell mass. Furthermore, CgA in serum
      increased during omeprazole treatment suggesting that serum CgA may be used as a
      test to evaluate ECL cell hyperplasia. A significant increase in basal and a
      marked (50%) and significant increase in pentagastrin stimulated acid secretion
      were found after treatment with omeprazole. CONCLUSIONS: Increased acid secretion
      after a conventional treatment period with a proton pump inhibitor is probably
      due to ECL cell hyperplasia and may have negative consequences for acid related
      diseases.

PMID- 9026478
TI  - Aspirin related gastrointestinal bleeders have an exaggerated bleeding time
      response due to aspirin use.
AB  - BACKGROUND: Gastrointestinal bleeding is related to non-steroidal anti
      inflammatory drug (NSAID) use, especially aspirin, but only a small subset of
      users bleed. AIM: To look for risk factors or mechanisms whereby aspirin may
      promote gastrointestinal bleeding. PATIENTS: Sixty one patients with previous
      aspirin related upper gastrointestinal bleeding and 61 matched controls. METHODS:
      Patients and controls were given 375 mg of aspirin and sequential skin bleeding
      time and blood aspirin levels were measured. Additional studies included platelet
      lumiaggregation, von Willebrand factor, Factor VIII, and coagulation studies.
      RESULTS: Baseline skin bleeding time was similar in bleeders and controls, but
      bleeders had a more prolonged skin bleeding time after aspirin use. Hyper
      response was more frequent in bleeders (30% v 9.3%; p < 0.01) and was associated
      with more than one previous separate bleeding event and a lower packed cell
      volume during the preceding bleeding episode. No differences were found in other
      factors studied. Logistic regression analysis identified prolonged skin bleeding
      time after aspirin use as an independent factor contributing to aspirin related
      gastrointestinal bleeding (RR = 5.4; 95% CI: 1.8 to 17.1). CONCLUSIONS: 30% of
      patients with a history of aspirin related gastrointestinal bleeding have an
      exaggerated prolongation of skin bleeding time in response to aspirin, which may
      be a risk factor for bleeding. This intrinsic defect or to subclinical von
      Willebrand disease or different aspirin metabolism.

PMID- 9026479
TI  - Physiological control of cholecystokinin release and pancreatic enzyme secretion
      by intraduodenal bile acids.
AB  - BACKGROUND: The physiological relevance of duodenal bile acids in the control of
      cholecystokinin release and pancreatic enzyme secretion is still unknown. AIMS:
      To provide a near physiological situation by perfusing a bile acid mixture
      mimicking the individual endogenous bile acid composition of the person under
      investigation. For maximal reduction of endogenous bile output the CCK-A receptor
      antagonist loxiglumide was infused intravenously. SUBJECTS AND METHODS: Seven
      healthy volunteers were studied on four different days by a duodenal marker
      perfusion technique. The individual bile acid composition in duodenal juice and
      test meal stimulated bile acid output was assessed on day 1. Bile acids were
      perfused at an amount of 30 or 100% as determined on day 1 in combination with
      the test meal in the presence or absence of loxiglumide. Pancreatic enzymes,
      bilirubin, and bile acid output were determined in duodenal juice. Plasma
      cholecystokinin (CCK) and plasma pancreatic polypeptide (PP) were measured
      radioimmunologically. RESULTS: Bile acid perfusion did not significantly alter
      stimulated pancreatic enzyme, bilirubin or bile acid output or plasma CCK.
      Loxiglumide did not alter basal CCK release but increased test meal stimulated
      CCK output fourfold (p < 0.05). The addition of bile acids to the test meal at a
      dose resembling 30% of bile acid output as determined on day 1 prevented this
      increase. Plasma PP concentration remained unchanged by bile acids and were
      mostly undetectable during loxiglumide infusion. CONCLUSIONS: The CCK producing
      cell is under constant suppression by intraduodenal bile acids which cannot be
      further enhanced by a physiological bile acid mixture. However, removal of
      duodenal bile acids by inhibition of gall bladder contraction unmasks this
      suppression leading to a dramatic increase in plasma CCK levels. As little as one
      third of postprandially released bile acids completely reverse this effect. Bile
      acids are the most important luminal regulator of CCK release in humans.

PMID- 9026480
TI  - Exocrine pancreatic insufficiency: accuracy and clinical value of the uniformly
      labelled 13C-Hiolein breath test.
AB  - BACKGROUND AND AIMS: The 13C-Hiolein breath test (98% [U-13C] labelled long chain
      triglyceride mixture (highly labelled triolein) was evaluated as a non-invasive,
      non-radioactive test for exocrine pancreatic insufficiency. Accuracy and clinical
      validity were examined with reference to both the secretin pancreozymin test and
      faecal fat analysis. METHODS: A secretin pancreozymin test and faecal fat
      analysis were performed in 46 patients, 30 with exocrine pancreatic insufficiency
      and 16 with normal pancreatic function. In all of these patients and in seven
      healthy volunteers (controls), a 13C-Hiolein breath test was performed using 2
      mg/kg [U-13C] labelled Hiolein with a standard risk snack (1.5 g/kg; 25% fat).
      13CO2/12CO2 enrichment in the exhaled breath was measured by isotope ratio mass
      spectrometry. RESULTS: In patients with pancreatic steatorrhoea the 13CO2
      response was below the 95% confidence interval of 13CO2 exhalation in the
      controls. These responses were also diminished (p < 0.001) compared with patients
      with impaired lipase output but normal fat excretion and with disease as well as
      healthy controls. There was a linear correlation between stimulated lipase output
      and the ratio of lipase output/13CO2 response (r = 0.95). Among the 40 patients
      in whom direct pancreatic function testing was clinically indicated, the
      sensitivity of the 13C-Hiolein test for detecting steatorrhoea was 91.7%, with a
      specificity of 85.7%. CONCLUSIONS: In patients with pancreatic disease the 13C
      Hiolein breath test reflects impaired lipase output and indicates decompensated
      lipolysis. The 13C-Hiolein breath test is a convenient alternative to faecal fat
      analysis.

PMID- 9026481
TI  - Pancreatitis associated protein as an early marker of acute pancreatitis.
AB  - BACKGROUND: Measuring serum pancreatitis associated protein (PAP) in acute
      pancreatitis has proved valuable to monitoring the course of the disease and the
      recovery of the patient. AIMS: The aim was to analyze the utility of PAP on
      admission as a diagnostic and prognostic marker of acute pancreatitis. PATIENTS:
      Values of PAP were prospectively analyzed in 80 healthy volunteers, 164 patients
      with abdominal pain but without pancreatitis, 109 patients with mild acute
      pancreatitis, and 38 patients with severe acute pancreatitis. METHODS: The
      diagnosis of acute pancreatitis was verified with clinical, laboratory,
      radiological, and in some cases findings at operation or necropsy. RESULTS: Mean
      (95% confidence intervals) serum PAP values were 27 (24 to 29) micrograms/l in
      healthy volunteers, 78 (59 to 96) micrograms/l in patients with abdominal pain,
      191 (134 to 247) micrograms/l, in patients with mild acute pancreatitis, and 599
      (284 to 914) micrograms/l in patients with severe acute pancreatitis. Differences
      between the groups were significant (p = 0.04 - 0.01). Despite the differences in
      means, the ranges overlapped between the groups. The sensitivity of PAP on
      admission to detect acute pancreatitis was 38%-53% and the respective specificity
      89%-77% depending on the cut off level. The sensitivity of PAP to detect severe
      acute pancreatitis was 45%-68% and the specificity 74%-59% depending on the cut
      off level. CONCLUSIONS: Admission PAP did not distinguish severe from mild acute
      pancreatitis better than C reactive protein. Measurement of PAP does not give
      appreciable diagnostic advantages in the early phase of acute pancreatitis.

PMID- 9026482
TI  - Combination thymosin alpha 1 and lymphoblastoid interferon treatment in chronic
      hepatitis C.
AB  - BACKGROUND: Monotherapy for chronic hepatitis C using interferon (IFN) results in
      a very small proportion of patients exhibiting a sustained response. Clinical
      trials assessing the benefit of combination drug therapy may provide evidence of
      improved treatment response over that seen with single drug treatment. AIM: To
      assess the response in patients with chronic hepatitis C to one year of
      combination treatment: thymosin alpha 1 (T alpha 1), 1 mg twice weekly, and
      lymphoblastoid (L)-IFN, 3 MU thrice weekly. PATIENTS AND METHODS: Fifteen
      patients with serum HCV RNA positive chronic hepatitis C were studied. Eleven
      patients were treatment naive and four had failed previous standard IFN therapy.
      Thirteen patients were HCV RNA serotype 1b. All patients were given combination T
      alpha 1 and L-IFN therapy for one year with a six month follow up period.
      RESULTS: Six months after initiation of treatment seven patients (47%) were sera
      HCV RNA negative and at completion of the one year treatment 11 (73%), including
      two who had failed previous standard IFN treatment, had negative serum HCV RNA.
      Six months after treatment, six patients (40%), including five with HCV type 1b,
      showed a sustained response characterized by a negative serum HCV RNA.
      CONCLUSIONS: The results of this open label trial suggest that there may be a
      potential benefit to combining an immune modulator (T alpha 1) with an antiviral
      (IFN) in the treatment of chronic hepatitis C. Verification of the observations
      in this study require completion of a randomised controlled study.

PMID- 9026484
TI  - Alveolar echinococcosis of the liver: percutaneous stent therapy in Budd-Chiari
      syndrome.
AB  - BACKGROUND AND AIMS: Infiltration of the hepatic veins in the alveolar
      echinococcosis can lead to the development of the Budd-Chiari syndrome. The
      medical and surgical treatment of this condition is generally unsatisfactory. The
      results of successful interventional treatment with percutaneous stent
      implantation in the hepatic veins are reported. METHODS: Using a transjugular
      approach, metal mesh stents (Boston Scientific, Medi-Tech Accuflex 8/60 mm) were
      placed in the median and left hepatic veins of a 53 year old woman. After the
      intervention, oral chemotherapy with albendazole (2 x 400 mg/day) was continued,
      but no anticoagulants were given. RESULTS: Stent placement was performed without
      complications. The clinical picture improved rapidly: normalisation of portal
      blood flow was confirmed by Doppler ultrasound and there was improvement of liver
      function, reduction of oesophageal varices, and disappearance of ascites. A
      follow-up examination at 15 months showed no evidence of stent occlusion.
      CONCLUSIONS: Treatment of portal hypertension in alveolar echinococcosis of the
      liver is problematic. In selected patients with portal hypertension secondary to
      hepatic vein stenoses but no cirrhosis, percutaneous stent placement in the
      hepatic veins represents a promising treatment alternative.

PMID- 9026483
TI  - Increased production of tumour necrosis factor-alpha interleukin-1 beta, and
      interleukin-6 by morphologically normal intestinal biopsies from patients with
      Crohn's disease.
AB  - BACKGROUND: Increasing evidence points to a important role for inflammatory
      cytokines for the pathogenesis of Crohn's disease. AIM: To compare the secretion
      rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta)
      and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa
      from patients with Crohn's disease. RESULTS: Organ cultures of intestinal biopsy
      specimens taken from areas of affected mucosa from patients with Crohn's disease
      spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6
      compared with controls but also biopsy specimens taken in macroscopically and
      microscopically unaffected areas in the same patients. Concentrations of IL-1
      beta and IL-6 measured in the supernatant fluid of biopsy cultures were
      positively correlated with the degree of tissue involvement measured by both
      endoscopic and histological grading. By contrast, TNF-alpha concentrations were
      not correlated to endoscopic and histological grading. CONCLUSIONS: These
      consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing
      mucosa from patients with Crohn's disease provide evidence for a sustained immune
      stimulation in Crohn's disease even in the absence of patent inflammation. The
      results shed a new light on the role of inflammatory cytokines in the onset of
      intestinal tissue damage in Crohn's disease and suggest that the range of
      intestinal lesions in Crohn's disease may be wider than suspected on the basis of
      regular endoscopic and histological examinations.

PMID- 9026485
TI  - New Aspects of Haemophilia Treatment. Proceedings of the 3rd symposium.
      Copenhagen, Denmark, September 21-23, 1995.

PMID- 9026486
TI  - [Ulnodorsal impingement syndrome: meniscus lesions of the wrist].
AB  - In a consecutive series of 166 wrist arthroscopies, a lesion of the meniscus was
      found in 16 patients. All of them complained of ulnar wrist pain evoked by axial
      load in extension. 14 patients had previous wrist trauma. The preoperative
      physical examination showed marked ulnodorsal tenderness on palpation and the
      examiner could feel crepitation by passive motion in the radial-ulnar direction.
      The meniscus represents a part of the triangular fibrocartilage complex (TFCC).
      At this time it is not possible by magnetic resonance imaging (MRI) to
      differentiate between articular disc and meniscus lesion. In contrast the two
      structures are clearly identifiable by arthroscopy especially if there is a
      radial tear through the meniscus or even a complete avulsion from its insertion
      on the palmar aspect of the triquetrum. The avulsed part of the meniscus can
      prolapse into the ulnocarpal joint, causing an impingement phenomenon.

PMID- 9026487
TI  - [Arthroscopic image of wrist joint instability].
AB  - In a consecutive series of 107 arthroscopies, 88 wrists showed a ligamentous
      lesion on the ulnar side. The TFCC was affected in 90% (79 patients), the
      triquetrum in 53% (47 patients), the ulnocarpal ligaments in 22% (19 patients)
      and the hamate in 17% (15 patients). The number of ligament injuries averaged
      three per wrist. Surprisingly, there were multiple lacerations noted in 22% of
      the TFCC and these occurred in characteristic combinations.

PMID- 9026488
TI  - [Functional treatment of the interphalangeal joints in palmar ligament rupture].
AB  - Palmar plate injuries of the interphalangeal joints are very common, yet they
      require careful treatment until full functional recovery is attained. This paper
      presents the results of follow-up examinations of 76 patients who underwent early
      functional treatment with a special dynamic splint. All had sustained an injury
      of the palmar plate of the PIP-joint (Type 1 or 2 according to Hintringer and
      Leixnering). After a velcro strip is released, the splint enables daily active
      exercise of the PIP joint with the joint being protected laterally and protected
      against hyperextension. This splint was worn for four weeks. After removal of the
      splint, 71% of all patients indicated that they did not have any problems, while
      26% achieved the same mobility as the unaffected joint of the other hand after
      two more weeks of dynamic splinting. In only one case motion was inhibited for
      several further weeks.

PMID- 9026489
TI  - [Results of conservative treatment of bony palmar plate avulsion of the middle
      joint (type I and type II according to Hintringer and Leixnering)].
AB  - At the Unfallkrankenhaus Lorenz Bohler, avulsion fractures of the palmar plate of
      the proximal interphalangeal (PIP) joint type I the and II are treated by
      immobilisation in a PIP-Stack splint. We use 147 the classification of Hintringer
      and Leixnering (1991). The were immobilised for three weeks. For follow-up, 102
      patients with 106 injured fingers from an overall of 147 patients treated by this
      method were investigated personally. 27 patients who could not attend, were
      evaluated by telephone. 22(17 to 25) months after the accident results were
      subjectively and objectively very good in 80% of the patients. In none of the
      patients extension was limited. In 18 patients, flexion was limited 5 to 10
      degrees, in two patients 15 to 20 degrees. No patient had a limitation of flexion
      of more than 20 degrees.

PMID- 9026490
TI  - [Conservative treatment of stable finger joint dislocations using the Stack
      splint].
AB  - Stable dislocations of PIP-joints should be treated by early motion. It is
      important to gain full extension from the very beginning of treatment. The
      anatomy and biomechanics as well as the use of a Stack button-hole splint is
      reported. 28 patients with 32 dislocations have been treated for two to four
      weeks with excellent results.

PMID- 9026491
TI  - [Functional results following surgical management of palmar fibrocartilagenous
      injuries].
AB  - Lesions of the palmar plate of PIP-joints were treated surgically during the past
      ten years in cases of dislocation of the PIP-joint, lesions to the collateral
      ligaments, or lesions to the extensor apparatus (according to types 3, 4 and 5 of
      Hintringer's classification). A followup of 97 patients showed nearly 90% good
      results in cases of ligamentous injuries, comparable to results after
      conservative treatment in other centres. In cases of fracture dislocation and
      open injuries, results were only fair. Conservative treatment is now preferred in
      most cases.

PMID- 9026492
TI  - [Status of the endoprosthesis in rheumatic metacarpophalangeal joints. Long-term
      results of metacarpophalangeal prostheses using Swanson's silastic spacers].
AB  - Advanced rheumatoid destruction of the metacarpophalangeal joints frequently
      requires implant arthroplasty. Among many different types of implants, the
      Swanson-Silastic-spacer is widely used. The long-term results of 102
      arthroplasties of the metacarpophalangeal joint were assessed in 28 rheumatoid
      patients (34 hands) 10.1 years postoperatively on the average. Marked relief of
      pain was found in all patients. 75% of the patients reported functional
      improvement of the hand. Active range of motion decreased from 42 degrees
      preoperatively to 36 degrees postoperatively on the average. Ulnar drift was
      corrected from an average of 34 degrees preoperatively to 12 degrees
      postoperatively. The average extension deficit had improved from 33 degrees at
      surgery to 11 degrees at the time of follow-up. Grip strength remained unchanged.
      The radiographical findings showed surrounding osteolysis in 89.4% of the
      implants and 27.5% broken spacers. In comparison to other types of finger
      implants, Silastic-spacers showed similarly limited all over results, however,
      there seem to be less problems in salvage procedures.

PMID- 9026493
TI  - [Flexor pulleys of the fingers. Anatomy, biomechanics, reconstruction].
AB  - Primary or secondary flexor tendon surgery occasionally leads to damaged flexor
      pulleys. Insufficient pulley reconstruction causes loss of finger function by bow
      stringing of the flexor tendon. This paper reviews the anatomy and biomechanics
      of the flexor pulley system. Different techniques of reconstruction are
      discussed.

PMID- 9026494
TI  - [Misinterpretation of a solitary breast carcinoma metastasis of the hand as an
      enchondroma. Case report and literature review].
AB  - Carcinoma of the breast is the third most common primary tumor leading to
      metastases in the hand. It is preceded by carcinoma of the lung and kidney. A
      review of literature is presented, following the case report of an isolated
      skeletal metastasis in the middle phalanx of the left ring finger in a 67-year
      old patient seven years after mastectomy of the right breast. At first, the
      findings were misinterpreted as enchondroma.

PMID- 9026495
TI  - [Sexual problems--possible counseling by the general physician].
AB  - This short review discusses the sexual problems most frequently encountered in
      the general practitioner's office, together with their respective possible
      backgrounds and therapeutic approaches. The aim of the paper is to draw attention
      to the significance of medical sexual problems for the subjective quality of life
      of the patient, and to encourage the family doctor to adopt a more active
      approach to the sexual concerns of his patients.

PMID- 9026496
TI  - [Herpes neonatorum--prevention and therapy. Which newborn infants are at risk?
      When cesarean section, when acyclovir?].

PMID- 9026498
TI  - [Insomnia--diagnostic and therapeutic procedure. 2: Non-medicamentous and
      medicamentous therapy in general practice].

PMID- 9026497
TI  - [Chronic venous insufficiency--from pathophysiology to therapy. 4: Treatment of
      ulcus cruris--therapy guidelines].
AB  - In the field of phlebology and angiology, leg ulcer represents a complex
      diagnostic and therapeutic problem. The initial steps include the taking of a
      careful history, inspection and palpation, and thorough angiological
      investigation which, where the individual situation makes this necessary, must be
      supplemented by such further diagnostic measures as biopsy, laboratory
      investigations or even allergy tests. Subsequent treatment must be stage-matched
      and must meet the individual needs of the patient. Both conservative and surgical
      forms of treatment are available.

PMID- 9026499
TI  - [Medical-naturopathy curriculum in education. Introduction and organization of
      the medical-naturopathy curriculum from the Middle Ages into the 19th century].
AB  - A source-oriented research study that began with medieval library catalogs,
      provided the material needed to establish the organization and structuring of the
      teaching of natural science in monastic/convent schools. The further development
      of natural science from here to present-day teaching of biology was then traced.
      The wealth of material available since the late Middle Ages enabled the
      individual phases of development of this new teaching subject to be identified
      and their adoption into the Latin education system determined. This process
      revealed a series of different establishment phases. From the Middle Ages
      onwards, the study is based on teachers' and pupils' books known to have been
      used in the Latin education system, and, from the 18th Century onward, on an
      additional 7,000 or so school annual reports as well as, from the second part of
      the 19th Century, teaching curricula.

PMID- 9026500
TI  - Medichem Proceedings 1995: 23rd Congress on Occupational and Environmental Health
      in the Chemical Industry. Cambridge, Massachusetts, 19-22 September 1995.

PMID- 9026501
TI  - Kinin '95. Proceedings of the 14th International Symposium on bradykinin and
      related kinins. Denver, Colorado, 10-15 September 1995.

PMID- 9026503
TI  - Re: Gehrmann, J. Colony-stimulating factors regulate programmed cell death of rat
      microglia/brain macrophages in vitro.

PMID- 9026502
TI  - Anchorage-dependent cell cycle progression.

PMID- 9026504
TI  - [Vaginal administration prostaglandin E2 in premature ruptured membranes at term
      with an unfavorable cervix].
AB  - AIM OF THE STUDY: To compare immediate labor induction by vaginal prostaglandins
      to immediate labor induction by oxytocin or to expectant management in case of
      prelabor rupture of the membranes at term. MATERIAL AND METHODS: A meta-analysis
      of all randomized trials indexed in Medline or in the Cochrane Database of
      Systematic Reviews comparing labor induction by vaginal prostaglandins to labor
      induction by oxytocin or to expectant management. The statistical analysis was
      performed according to Peto and Yussuf's modified Mantel Haenszel method. The
      results were expressed as odds-ratios. RESULTS: Ten published studies meeting the
      above criteria were found. These trials included 1004 patients. When comparing
      labor induction by prostaglandins to expectant management, we observed a
      reduction of the admission-to-delivery interval, a decreased maternal and
      neonatal infection rate, without difference in the cesarean section rate. When
      comparing labor induction by vaginal prostaglandins to labor induction by
      oxytocin, a decreased cesarean section rate was observed without difference in
      maternal or neonatal infection rates. CONCLUSION: Immediate labor induction by
      vaginal prostaglandins provides better maternal and neonatal outcomes than labor
      induction by oxytocin or expectant management in case of prelabor rupture of the
      membranes at term.

PMID- 9026505
TI  - [Pure 46XY gonadal dysgenesis].
AB  - 46 XY pure gonad dysgenesia, also known as Swyer syndrome, is a disorder of
      sexual differentiation. The patients are phenotypic females with a 46 XY
      karyotype and hypoplastic gonads without germ cells. They present most often with
      primary amenorrhea. The study of this abnormality in testicular differentiation
      contributed to the identification of the gene SRY, testis determining factor. To
      date, 20% of 46 XY pure gonad dysgenesia are explained by a mutation or a
      deletion in SRY. In 80%, SRY is apparently normal. The risk of gonadal neoplasia
      is high, dictating early prophylactic removal of these dysgenetic gonads.
      Gonadoblastoma and dysgerminoma are the most frequently reported malignancies.
      Because of the possible inheritance of XY gonad dysgenesia all family members
      should undergo a thorough screening.

PMID- 9026506
TI  - [Ovarian goiter with hyperthyroidism. A case report].
AB  - We report a case of ovarian goiter associated with hyperthyroidism. We insist
      upon their rarity and the difficulty of preoperatory diagnosis. Prognosis is good
      after surgery.

PMID- 9026507
TI  - [Umbilical metastasis of an endometrial adenocarcinoma: "Sister (Mary) Joseph's
      nodule". Review of the literature].
AB  - In the beginning of the XXth century, Sir Hamilton Bailey proposed the name
      "Sister Joseph's nodule" for the umbilical metastasis of an abdominal cancer.
      This unusual pathology has multiple primitive etiologies. We report here the 27th
      case of an umbilical metastasis of an endometrial adenocarcinoma. In case of a
      malignant umbilical tumor, 75% correspond to a "Sister Joseph's nodule". Their
      clinical manifestations are quite similar. This secondary localisation could
      appear before, during or after the diagnosis of the primitive tumor.
      Adenocarcinoma is the frequently diagnosed histological type. The endometrial
      origin represents only 1.4% of the cases. Multiple routes of spread exist.
      Prognosis remains poor. Medico-surgical treatment, in a curative target, will be
      aggressive and should be adapted at every case. Our case-report recalls a new
      patho-physiological approach. The extended follow-up of this patient, without
      further medical treatment, is an additional argument.

PMID- 9026508
TI  - [Treatment of ectopic pregnancies by laparotomy in under-equipped countries. A
      series of 144 cases at the Yaounde University Hospital Center (Cameroon)].
AB  - We report in the context of a developing country the results of ectopic
      pregnancies treated by laparotomy in the last ten years (1984-1993) in the
      maternity unit of the Teaching Hospital Yaounde (Cameroons). There were 144 cases
      of ectopic pregnancies from a total of 12,507 deliveries; this corresponds to 11
      cases of ectopic pregnancies for 1,000 deliveries. In 75 cases (52%) the patients
      were operated in emergency situations with clinical signs of ruptured ectopic
      pregnancy which were later confirmed at laparotomy. In 69 cases (47.9%) the
      patients were retained in hospital for definitive diagnosis and in the follow-up,
      the diagnosis was confirmed by laparoscopy in 37 cases (53.6%) and by
      ultrasonography in 22 cases (31.9%). In this study the frequency of ectopic
      pregnancy was most common among primiparous women (36 cases) and second parity
      (37 cases). The highest frequency of ectopic pregnancies was found in women in
      the age range between 25 and 30 years. Radical treatment of ectopic pregnancy was
      performed in 62 cases (43.0%) and conservative treatment in 82 cases (56.9%). The
      main complication during the operation was represented by severe hemorrhage in 65
      cases (45.1%); blood transfusion was required in 25 cases. Among the patients who
      were followed up in the prenatal clinic (98 cases) 16 patients (16.3%) presented
      an intra-uterine pregnancy and 12 patients (12.2%) a recurrence of ectopic
      pregnancy. Ectopic pregnancy is a frequent pathology in Cameroon. In the absence
      of methods for early diagnosis of ectopic pregnancy such as endovaginal
      ultrasonography and the measurement of beta human chorionic gonadotropin (beta
      hCG), primary use of laparotomy is necessary when clinical signs of ectopic
      pregnancy exist. This procedure permits the avoidance of severe complications
      such as hemorrhage and maternal death. It can be said that laparotomy still has
      its place in the treatment of ectopic pregnancy in developing countries.

PMID- 9026509
TI  - [Risk factors for child abuse during the perinatal period. Preventive approach in
      the obstetric milieu. Role of a child abuse risk index].
AB  - OBJECTIVE: We studied the frequency of maltreatment of the newborn child and
      offered a preventive action plan. DESIGN: We conducted a retrospective study, on
      a semi-rural population, during three years period during which 2,198 deliveries
      took place. A number of severely maltreated new-born children were observed. Then
      we conducted for a two years period a prospective study of 1,007 pregnancies. A
      score of maltreatment risk was designed, which permitted to offer appropriate
      follow up to high risk couples. RESULTS: In the retrospective study 39 cases of
      maltreatment of newborn infants (1.8%) were observed. The average score was 9.7.
      In the control group realised during the prospective study, the average score was
      0.7. No cases of maltreatment was noted. CONCLUSION: This study validates our
      approach which involves several institutions to take care of high risk couples
      during pregnancy with the aim to prevent maltreatment of the newborn.

PMID- 9026510
TI  - [Value of the systematic uterine Doppler in the primiparous woman. A series of
      315 cases].
AB  - OBJECTIVE: This retrospective study was designed to assess the screening of pre
      eclampsia (PE) and intra-uterine growth retardation (IUGR) by uteroplacental
      doppler scan in a population of primiparous, selected in a hospital having 700
      deliveries each year. STUDY DESIGN: We studied, a consecutive series of 315
      primiparous women at 19 weeks (gestational age) screened by pulsed Doppler of
      uterine artery. Group A (normal uterine artery Doppler) was compared with group B
      (pathological uterine artery Doppler) for pregnancy-induced hypertension,
      preeclampsia and intra-uterine growth retardation (chi 2 test and Fisher test).
      RESULTS: Group B included 50 patients (15%). They had more hypertensive
      pathologies (24%) (p < 0.001) and IUGR (20%) (p < 0.005) were more frequent than
      the group A (265 patients: 85%) which had only 7.2% and 8.2% respectively. In
      this study, the sensitivity of uterine artery Doppler was 34.3%, the specificity
      was 88.5%, the positive predictive value was 42%, the negative predictive value
      was 84.9% for all hypertensive disorders. CONCLUSION: The contribution of this
      examination is doubtful in a low risk population where the prevalence of
      complications is low and the VPP is about 10 to 14% for preeclampsia. On the
      other hand, test predictivity reaches 50% for all dysgravidic disorders.

PMID- 9026511
TI  - [Smoking and pregnancy: search for a correlation between cotininemia and Doppler
      findings].
AB  - OBJECTIVE: To search for a possible correlation between an effective marker of
      smoking and uterine and placental resistance during pregnancy. STUDY DESIGN: A
      prospective study was conducted at the Intercommunal Hospital Center of
      Montreuil, France: 81 healthy pregnant women underwent uterine and placental
      Doppler and cotidin blood assay, the best current test for smoking. RESULTS: This
      study shows a significative increase of utero-placental vascular resistances
      according with increased cotidine levels. CONCLUSIONS: The previously observed
      association between smoking and perinatal events most likely involves vascular
      resistance of uterus and placenta.

PMID- 9026512
TI  - [Pregnancy in primary antiphospholipid syndrome. Proposal for a common management
      protocol].
AB  - OBJECTIVE: Primary antiphospholipid syndrome (APS) is by definition associated
      with high obstetric risk. We performed a retrospective study of pregnancies in
      women with this syndrome in an attempt to define a common means of caring these
      patients. STUDY DESIGN: Women with APS followed in Internal Medicine Department
      and in Gynecology Department since 1989 were studied retrospectively. RESULTS:
      Fifteen women with primary APS had a total of 51 pregnancies, 39 (76%) of which
      ended in embryonic (n = 24) or fetal (n = 15) loss. Only 6/39 untreated
      pregnancies led to a live birth, including 2 cases of intrauterine growth
      retardation. Among the 12 pregnancies treated preventively for obstetric
      complications, 6 led to a live birth. The treatments used were dissimilar and
      included aspirin, corticosteroids and heparin, either alone or in association.
      Four of these 6 live births were obtained by aspirin alone. Gravidic toxemia was
      observed in one untreated patient. CONCLUSION: The obstetric prognosis for
      untreated APS is appalling. The benefit of heparin therapy in association with
      aspirin remains to be demonstrated, ideally in a protocol comparing aspirin alone
      with aspirin and heparin.

PMID- 9026513
TI  - [Gamstorp's disease and pregnancy. A case report].
AB  - Gamstorp's disease or hyperkaliemic periodic paralysis is a rare pathology
      leading to spells of generalized hypotonia due to hyperkaliema. It is hard to say
      how far pregnancy affects the course of the disease and what is the impact of the
      disease on pregnancy. We report a case of Gamstorp's disease during pregnancy and
      we insist on the fact that because it can be crippling during its acute phases,
      close surveillance is needed during pregnancy. Screening for malignant
      hyperthermia should be carried out. During labour, kaliemia level should be
      monitored repeatedly and the expulsion phase kept as short as possible if
      necessary by forceps delivery.

PMID- 9026514
TI  - [May-Heggelin anomaly and pregnancy. A case report, review of the literature].
AB  - The May-Hegglin anomaly is a rare autosomal dominant platelet disorder
      characterized by thrombocytopenia, giant platelets and existence of crescent
      shaped inclusions within the cytoplasm of granulocytes, eosinophils and monocytes
      (Dohle body). We report a case of May-Hegglin anomaly associated with a
      pregnancy. The pregnancy and delivery were uneventful. The child is not a carrier
      of this hematologic anomaly. Nine cases of complicated pregnancies with this
      anomaly have been reported in the literature. The risks of maternal hemorrhagic
      accident during pregnancy and during delivery are weak due to the fact that
      platelets functions are preserved. The same applies to the fetus. Nevertheless,
      as in the case of maternal autoimmune thrombocytopenic purpura, most reports
      advice performing a fetal platelet count on fetal blood sampling before birth to
      decide upon the mode of delivery. The risk of the cordonal approach to perform
      fetal blood sampling must be balanced against the small fetal hemorrhagic risk
      and most authors propose to allow normal delivery whilst avoiding all traumatic
      instrumental extraction, especially the use of vacuum extractor.

PMID- 9026515
TI  - [Cord prolapse. Review of the literature. A series of 50 cases].
AB  - OBJECTIVES: Identify the role of cord prolapse in modern obstetrics by estimating
      the frequency of this obstetrical accident, its conditions, prognosis and
      treatment and by analyzing factors favoring development of cord prolapse. METHOD:
      From a retrospective study of 50 observations of cord prolapse occurring in the
      department of obstetrics from January 1985 to June 1994. Results were compared
      with those reported in the literature. RESULTS: The frequency of cord prolapse
      was 0.21% over the 10-year period. Cesarean section was required in 72% of the
      cases, and obstetrical manoeuvers were used in some of the vaginal deliveries
      (28%). Neonatal mortality was 20/1000. Predisposing factors were breech
      presentation, prematurity, twin pregnancy and multiparity. CONCLUSION: Despite
      much progress in obstetrics, the frequency of cord prolapse has not changed over
      time. The consequences are not as lethal as in the past, because of progress in
      diagnosis and neonatal resuscitation. Fetal prognosis remains however severe.

PMID- 9026516
TI  - [Prophylactic cesarean section and HIV seropositive patients].
AB  - OBJECTIVES: HIV infection among children is essentially related to perinatal
      transmission. It seems the contamination occurs late in the pregnancy or during
      the labor. The benefits of cesarean section in HIV-infected women has to be
      examined. STUDY DESIGN: A retrospective survey of all deliveries of 292 HIV
      infected women, of the newborns and of the impact of different ways of delivery
      on transmission risks. 164 women had a pregnancy lasting more than 28 weeks, 27
      underwent a cesarean section. RESULTS: 22.2% of patients who underwent a cesarean
      section contaminated their child, 25.2% among vaginal deliveries. No significant
      association was found between HIV transmission and delivery mode. CONCLUSION: We
      outline the necessary elements for the conduct of a conclusive efficacy trial of
      operative versus vaginal delivery.

PMID- 9026517
TI  - [Postpartal ovarian thrombophlebitis. Value of Doppler ultrasonograph y].
AB  - Thrombophlebitis of the ovarian vein is a well recognized but uncommon
      complication during the postpartum period. We report a small series and emphasize
      the contribution of color Doppler and the basic therapeutic measures.

PMID- 9026519
TI  - [Embryonal implantation. Fundamental and practical aspects].
AB  - The precise mechanisms of embryo implantation remain unclear: the uterus is a
      "hostile environment" which should become "neutral" at the time of implantation.
      Advances have been made both in terms of embryo quality and in implantation
      techniques, making better knowledge of the uterus-embryo dialogue essential. To
      meet this challenge, the Pharmaceutical firms Serono France and ARCEFAR have
      organized a symposium entitled "Embryo implantation: basic principles and
      practical aspects". The symposium, presided by Andre Hazout and Yves Menezo, will
      first focus on the fundamental role of the ovum then will explore the complex
      immunological processes involved in the uterus-embryo dialogue.

PMID- 9026518
TI  - [Maternal paralysis of obstetrical origin. Two case reports].
AB  - We report two cases of maternal obstetrical paralysis by injuries to the sacral
      plexus (lumbosacral trunk). This nervous lesion is rare and occurs more often in
      young small primigravidae, carrying a large fetus, during a prolonged labor and a
      delivery requiring midforceps. The symptoms appear usually a few hours after
      delivery: paresthesias of the leg and the foot as well as weakness and possible
      footdrop (the paralysis may be mild or severe). The different mechanisms involved
      are inspected. The prognosis of this lesion is good, the patients recover usually
      within a period of three months. The treatment appears to be physiotherapy.

PMID- 9026520
TI  - [Obstetrics-gynecology training].

PMID- 9026521
TI  - Endotoxin, TNF, and IL-1 decrease cholesterol 7 alpha-hydroxylase mRNA levels and
      activity.
AB  - Endotoxin (LPS) and cytokines increase cholesterol synthesis and the secretion of
      lipoproteins by the liver in rodents resulting in hypercholesterolemia.
      Cholesterol 7 alpha-hydroxylase (CAH) is the rate-limiting enzyme in the
      conversion of cholesterol to bile acids in the liver, the major regulated pathway
      by which cholesterol is eliminated from the body. Decreases in CAH would increase
      the quantity of cholesterol available for lipoprotein production. In the present
      study, we demonstrate that LPS, TNF, or IL-1 administration to Syrian hamsters
      produces a marked decrease in the levels of CAH mRNA in the liver. This marked
      decrease occurred even when the basal level of CAH expression was increased by
      feeding the bile acid sequestrant, colestipol. Additionally, a marked decrease
      was also observed when the animals were fed a cholesterol-enriched diet.
      Moreover, the decrease in CAH mRNA occurred very rapidly (decreased 66% by 90 min
      after LPS administration) and required relatively small doses of LPS (100 ng/100
      g body weight). Lastly, the decrease in mRNA levels was accompanied by a decrease
      in CAH activity. This decrease in CAH could contribute to the increase in hepatic
      lipoprotein production induced by LPS and cytokines. CAH can be added to the
      growing list of proteins that regulate lipid metabolism and that are altered
      during the acute phase response.

PMID- 9026522
TI  - Effects of streptozotocin-induced diabetes on low density lipoprotein receptor
      expression in rat adipose tissue.
AB  - Low density lipoprotein (LDL) receptors are found in most cells, including
      adipose cells. LDL receptors are primarily regulated by cellular cholesterol
      content. Insulin and insulin deficiency have been reported to have varying
      effects on LDL receptors in various tissues. The present study was undertaken to
      assess the in vivo effects of streptozotocin-induced diabetes on LDL receptor
      expression and cholesterol content in adipose tissue and liver, Diabetes was
      induced by a single dose of streptozotocin. After 3 days, some animals were
      treated with insulin, and all animals were killed 10 days after induction of
      diabetes. Compared to control rats, 10 days of diabetes caused a decrease in
      adipose cell size and cellular unesterified cholesterol and cholesteryl esters,
      and insulin treatment returned these towards normal. No changes were observed in
      hepatic lipid content with diabetes or insulin treatment. Diabetes was associated
      with an approximately 50% reduction in immunoreactive LDL receptors in adipose
      cells (P < 0.01) that was returned to normal with insulin treatment. The levels
      of LDL receptor mRNA decreased approximately 80% (P < 0.001) in adipose cells
      isolated from streptozotocin-induced diabetic rats and returned to normal with
      insulin treatment. Hepatic LDL receptors and mRNA levels were unaffected by
      diabetes or insulin treatment. In conclusion, diabetes decreased LDL receptor
      expression in adipose cells while total cellular cholesterol content also
      declined.

PMID- 9026523
TI  - Isoproterenol decreases LDL receptor expression in rat adipose cells: activation
      of cyclic AMP-dependent proteolysis.
AB  - The low density lipoprotein (LDL) receptor is part of a family of proteins that
      mediate the uptake of lipoproteins into cells. In this paper we have demonstrated
      the over-expression in E. coli of a rat LDL receptor fusion protein that contains
      the region of the receptor sharing homology with the EGF precursor. The fusion
      protein was utilized to immunize rabbits and successfully generate antibodies
      that recognize the intact LDL receptor. These anti-LDL receptor/fusion protein
      antibodies were used to examine the effects of cyclic AMP on the expression of
      LDL receptors in isolated rat adipocytes. Incubation of adipocytes with
      isoproterenol caused a dose-dependent diminution in intact LDL receptors in the
      plasma membrane with the concomitant appearance of smaller immunoreactive
      proteins. Pulse-chase experiments demonstrated that isoproterenol rapidly
      shortened the initial half-life of intact, immunoprecipitable LDL receptors in
      the plasma membrane. The effects of isoproterenol on LDL receptor expression were
      mimicked by forskolin, by an analog of cyclic AMP, and by ACTH. In contrast,
      incubation with propranolol blocked the effects of isoproterenol on LDL receptor
      expression. While antioxidants and several different protease inhibitors had no
      effects, N-acetyl-leucine-leucine-methionine (ALLM) was able to prevent the
      isoproterenol-induced effects on LDL receptors. Thus, it appears that agents
      acting via cyclic AMP cause a rapid decrease in LDL receptors in the plasma
      membranes of isolated adipose cells due to the apparent stimulation of an ALLM
      sensitive protease that degrades the LDL receptor. These results suggest a novel
      mechanism for the posttranscriptional regulation of LDL receptor expression in
      adipocytes.

PMID- 9026524
TI  - Carotenoids in biological emulsions: solubility, surface-to-core distribution,
      and release from lipid droplets.
AB  - Data on the physico-chemical properties of carotenoids in biological emulsions
      are essential to our knowledge of carotenoid metabolism. Therefore, we determined
      the behavior of carotenoids in phospholipid-stabilized triglyceride emulsions, a
      model for biological emulsions such as dietary emulsions, triglyceride-rich
      lipoproteins, and intracellular storage droplets. The solubility of beta-carotene
      (a model for apolar carotenoids, carotenes) in pure bulk triglycerides (0.112 to
      0.141 wt % according to triglycerides) was significantly higher than zeaxanthin
      (a model for polar carotenoids, xanthophylls) (0.022 to 0.088 wt %). The
      solubility of both carotenoids increased when the chain-length of the
      triglycerides' fatty acids decreased. The amount of zeaxanthin associated with
      lipid droplet dramatically increased in phospholipid-triglyceride droplets as
      compared to the pure corresponding triglyceride droplets, whereas the amount of
      beta-carotene associated with lipid droplets increased only slightly beta
      Carotene distributed almost exclusively in the core of triolein-lecithin
      carotenoid droplets, while zeaxanthin distributed preferentially at the droplet's
      surface. A significant percentage (8.3%) of zeaxanthin was spontaneously
      transferred from lipid droplets to aqueous phase and the remaining part was
      transferred during triglyceride hydrolysis catalysed by pancreatic lipase, while
      beta-carotene absolutely required triglyceride lipolysis to be transferred to the
      aqueous phase. Our results show that polar and apolar carotenoids behave
      differently in biological emulsions. They further our understanding of the
      bioavailability of polar and apolar carotenoids and of their distribution between
      lipoprotein particles.

PMID- 9026525
TI  - Contribution of de novo fatty acid synthesis to very low density lipoprotein
      triacylglycerols: evidence from mass isotopomer distribution analysis of fatty
      acids synthesized from [2H6]ethanol.
AB  - A detailed comparison of the structures of plasma very low density lipoprotein
      (VLDL) and liver triacylglycerols (TG) (Yang et al. 1995. J. Lipid Res. 36: 125
      136) has demonstrated that a minimum of 60% of the secreted TG could have been
      derived from partial lipolysis and reesterification of stored TG and a maximum of
      40% could have been derived from direct secretion of newly made TG. To
      investigate the processes involved in the transfer of TG to VLDL in vivo, we have
      determined the distribution of deuterium among the molecular species of the liver
      TG and VLDL-TG during the infusion of perdeuterated ethanol along with fructose
      or glucose and during the provision of either glucose or fructose in the drinking
      water for 2 weeks. The deuterium labeling (percent excess and percent
      replacement) of the total fatty acids was determined by GC/MS of the methyl
      esters while the labeling of the glycerol and the glycerol plus fatty acids of
      the enantiomeric diacylglycerol moieties of TG was determined by LC/MS with on
      line mass spectrometry. Supplementation of the diet for 2 weeks with either
      glucose and fructose stimulated the synthesis of TG containing new fatty acids
      and glycerol. The proportion of the newly made to preexisting TG differed in VLDL
      from that in the liver. The 2H % replacement in glycerol and in total fatty acids
      was greater in VLDL-TG than in the liver-TG. On the basis of the mass isotopomer
      distribution analysis it was estimated that a maximum of 30% of the VLDL-TG could
      have been derived directly from TG that was made de novo and did not equilibrate
      with the liver-TG stores. The transfer of the stored TG to VLDL was best
      accounted for by a degradation to 2-monoacylglycerols and resynthesis via the 2
      monoacylglycerol pathway with addition of an excess of newly synthesized fatty
      acids to the resynthesized TG.

PMID- 9026526
TI  - Mode of growth hormone administration influences triacylglycerol synthesis and
      assembly of apolipoprotein B-containing lipoproteins in cultured rat hepatocytes.
AB  - Hypophysectomized female rats were treated for 1 week with thyroxine (10
      micrograms/kg.day), cortisol (400 micrograms/kg.day), and bovine GH (1 mg/kg.day)
      either as two daily subcutaneous injections (GH x 2) or as a continuous
      subcutaneous infusion (GHc) in order to mimic the male and female specific GH
      secretory patterns, respectively. Hepatocytes were then isolated and kept in
      short-term cultures. Hypophysectomy decreased the synthesis of triacylglycerol.
      Treatment with GH x 2 had no or small effects, while GHc normalized the effect of
      hypophysectomy. ApoB-100 VLDL was assembled before apoB-48 VLDL. ApoB-48 was
      first assembled as an HDL particle (apoB-48 "HDL"). Hypophysectomy decreased the
      proportion of intracellular apoB-48 that was recovered as VLDL. Moreover, the
      proportion of apoB-48 of total apoB in VLDL decreased. Only GHc fully restored
      the effect of hypophysectomy by inducing an 4-fold increase in the assembly of
      apoB-48 VLDL, while treatment with GH x 2 gave rise to a 1.8-fold increase.
      Hypophysectomy resulted in a decrease in the proportion of apoB-48 that was
      secreted as VLDL and a decrease in the proportion of apoB-48 of total apoB in
      VLDL. Only treatment with GHc fully restored the secretion of apoB-48 VLDL by
      inducing an almost 4-fold increase in the secretion of apoB-48 VLDL, while the
      corresponding value for treatment with GH x 2 was 1.7. However, GH x 2 increased
      the proportion of the secreted apoB-48 that was recovered in VLDL to the levels
      found in normal rats and in rats treated with GHc, but this finding was due to a
      failure of GH x 2 treatment to increase the secretion of apoB-48 "HDL". In
      summary, a continuous infusion of GH to hypophysectomized rats, mimicking the
      female secretion of GH, normalized the triacylglycerol synthesis and secretion as
      well as apoB-48 VLDL assembly and secretion to those levels observed in
      hepatocyte cultures from intact female rats.

PMID- 9026527
TI  - Differential mobilization of fatty acids from adipose tissue.
AB  - Are the different fatty acids mobilized into plasma in proportion to their
      concentrations in adipose tissue triglyceride? To answer this question, we fed
      weaning rabbits a special diet to label the fat stores with a variety of dietary
      fatty acids. The release of adipose tissue fatty acids into the plasma was then
      induced by ACTH-stimulated lipolysis. The compositions of the resulting plasma
      free fatty acids and of the adipose tissue triglyceride were then compared.
      Plasma free fatty acids increased from 625 mumol/L at baseline to 2938 mumol/L
      after ACTH and represented fatty acids released from adipose tissue. The relative
      mobilization of these fatty acids from adipose tissue was defined as the ratio
      between their percentage in the plasma free fatty acid fraction to their
      percentage in adipose tissue triglyceride. For the 24 fatty acids examined, the
      relative mobilization ranged from 0.11 for 22:1 n-11 to 5.06 for 20:5 n-3, a 46
      fold difference. Relative mobilization correlated positively with unsaturation
      and negatively with chain length. The relative mobilization for essential fatty
      acids was in the order of 20:5 n-3 > 20:4 n-6 > 18:3 n-3 > 22:6 n-3 > 18:2 n-6.
      Saturated fatty acids, along with oleic acid, were much less well mobilized than
      the entire group of polyunsaturated fatty acids. Our data indicate that the
      mobilization of fatty acids into plasma was not proportional to their content in
      adipose tissue, but rather was influenced by their molecular structure.
      Eicosapentaenoic acid 20:5 n-3 (EPA), and arachidonic acid 20:4 n-6, precursors
      of two different prostaglandins, were the fatty acids with the highest
      mobilization into the plasma.

PMID- 9026528
TI  - Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and
      postheparin lipases during gestation in women.
AB  - To understand the mechanism responsible for maternal hyperlipidemia, 25 healthy
      pregnant women were studied longitudinally during the three trimesters of
      gestation and at post-partum, and 11 were studied again at post-lactation.
      Triglyceride and cholesterol levels increased with gestation in all the
      lipoprotein fractions. However, the greatest change appeared in low density (LDL)
      and high density (HDL) lipoproteins, both of which showed an increase in their
      triglyceride/cholesterol ratio. The proportional distribution of HDL subfractions
      showed that the HDL2b fraction was the only one that increased with gestation,
      whereas both HDL3a and HDL3b had the greatest decrease. Cholesteryl ester
      transfer protein activity increased during the second trimester of gestation.
      While postheparin lipoprotein lipase activity decreased during the third
      trimester, postheparin hepatic lipase activity progressively decreased from the
      first trimester. The 17 beta-estradiol, progesterone, and prolactin hormones
      progressively increased from the first trimester of gestation. The lipoprotein
      triglyceride values correlated linearly and negatively with the logarithm of
      either postheparin lipase activities, HDL-triglycerides showing the highest
      correlation coefficient when plotted against the hepatic lipase values (r = 
      0.757). It appeared that the highest correlation between any of the HDL
      subclasses and the activity of the enzymes was for hepatic lipase activity versus
      HDL2b (r = 0.456) or HDL3a (r = 0.519). A significant lineal correlation also
      appeared between the postheparin hepatic lipase activity and the logarithm of any
      of the sex hormones studied, the highest value corresponding to estradiol (r = 
      0.783). Therefore, during gestation, the effect of estrogen in enhancing very low
      density lipoprotein (VLDL) production and decreasing hepatic lipase activity
      plays a key role in the accumulation of triglycerides in lipoproteins of density
      higher than VLDL.

PMID- 9026529
TI  - Lack of association of the apolipoprotein A-I-C-III-A-IV gene XmnI and SstI
      polymorphisms and of the lipoprotein lipase gene mutations in familial combined
      hyperlipoproteinemia in French Canadian subjects.
AB  - Familial combined hyperlipoproteinemia (FCH) is a common familial lipoprotein
      disorder characterized by elevated plasma cholesterol and triglyceride levels
      with segregation in first-degree relatives. Most affected subjects with FCH have
      elevated plasma levels of apolipoprotein (apo) B. The disorder results from
      oversecretion of hepatic apoB-containing lipoprotein particles. The genetic
      defect(s) are unknown. Previous work has suggested that genetic polymorphisms of
      the apoA-I gene and functional abnormalities of the lipoprotein lipase (LPL) gene
      are associated with FCH. We investigated the XmnI and SstI restriction fragment
      length polymorphisms (RFLP) of the apoA-I gene in FCH subjects of French Canadian
      descent. We also investigated three common functional mutations of the
      lipoprotein lipase (LPL) gene (LPLGly188Glu, LPLPro207Leu, and LPLAsp250Asn) in
      French Canadians that account for approximately 97% of cases of complete LPL
      deficiency in the province of Quebec, Canada. We identified and characterized 54
      FCH probands in lipid clinics and examined at least one first-degree relative.
      There were 37 men and 17 women (mean age 48 +/- 9 and 58 +/- 8 years,
      respectively). None of the probands had diabetes mellitus; mean plasma glucose
      was 5.5 mmol/L. High blood pressure was diagnosed in 32% of men and 29% of women.
      The body mass index (weight (kg)/height(m2)) was elevated in probands (27 +/- 4
      for men and 26 +/- 4 for women). Mean plasma levels of cholesterol (C) was 7.6 +/
      1.5 mmol/L, triglycerides 3.5 +/- 1.6 mmol/L, LDL-C 4.9 +/- 1.2 mmol/L, HDL-C
      1.0 +/- 0.3 mmol/L, and apoB 1.83 +/- 0.67 g/L in the probands. Allele frequency
      of the rare alleles of the XmnI and SstI RFLP was not significantly different
      from a healthy reference group. In several families studied, the XmnI and SstI
      RFLP did not unequivocally segregate with the FCH phenotype. There was no
      significant effect of the presence or absence of the XmnI or SstI RFLP's on
      plasma lipids, lipoprotein cholesterol or apoB levels. Only one FCH proband was
      found to have a mutation of the LPL gene (Gly188Glu), and this did not segregate
      with the FCH phenotype in the family. We conclude that in our highly selected
      group of FCH subjects of French Canadian descent, the XmnI and SstI RFLPs of the
      apoA-I gene and common functional mutations of the LPL gene resulting in complete
      LPL deficiency are not associated with FCH.

PMID- 9026530
TI  - Free and esterified oxysterol: formation during copper-oxidation of low density
      lipoprotein and uptake by macrophages.
AB  - We have defined the lipid composition of copper-oxidized LDL (Cu-oxLDL) and a
      macrophage-foam cell model generated by the uptake of this modified lipoprotein.
      An HPLC method previously developed by our group for the measurement of lipid
      oxidation products of LDL was extended to permit the analysis of an array of 7
      ketocholesteryl esters. Gas chromatography was used for the quantitation of
      oxysterols (free and esterified) in Cu-oxLDL and their subsequent uptake by
      macrophages. LDL (1.0 mg protein/ml) was oxidized using Cu(II) (20 microM) for up
      to 48 h at 37 degrees C. Resident mouse peritoneal macrophages were incubated
      with 24 h Cu-oxLDL (50 micrograms/ml) for 24 h. In 24 h Cu-oxLDL, cholesterol
      comprised approximately 50% of total sterols, 7-ketocholesterol comprised
      approximately 30% with five other oxysterols comprising the remainder (7 alpha-
      and 7 beta-hydroxycholesterol, cholesterol alpha- and beta-epoxides, and 6 beta
      hydroxycholesterol). Macrophages that were incubated with 24 h Cu-oxLDL displayed
      a profile of oxysterols remarkably similar to that of 24 h Cu-oxLDL itself. The
      majority of cholesteryl esters and 7-ketocholesteryl esters in Cu-oxLDL and in Cu
      oxLDL-loaded macrophages contained fatty acyl chains which are presumed oxidized.
      This work represents a comprehensive survey of free and esterified oxysterols in
      Cu-oxLDL and Cu-oxLDL-loaded macrophages and provides a basis for exploring how
      oxysterols are metabolized by macrophages and authentic human foam cells, and
      how, in turn, these oxysterols influence cellular metabolism.

PMID- 9026531
TI  - Fatty acid uptake by Caco-2 human intestinal cells.
AB  - The Caco-2 human enterocytic cell line was used to study the kinetics and
      mechanism of intestinal long chain fatty acid uptake. Initial rates of palmitate
      (16:0), oleate (18:1), and octanoate (8:0) uptake were determined for adherent
      cells at greater than 7 days confluence. Uptake of long chain 18:1 and 16:0 by
      cells grown on coverslips was saturable with an apparent Km of 0.3 microM, but
      also included a notable diffusive component. Uptake of short chain 8:0, on the
      other hand, was linear up to 10 microM. Cells grown on permeable Transwell
      filters were used to study uptake at the apical versus the basolateral membrane.
      Uptake of long chain (18:1 and 16:0), but not short chain (8:0), fatty acid was
      saturable at both surfaces with a similar Km of 0.3 microM. In addition, long
      chain but not short chain fatty acid uptake was competitively inhibitable.
      Western blot analysis demonstrated that Caco-2 cells express a protein
      immunoreactive with antibodies to the rat liver plasma membrane fatty acid
      binding protein (FABPpm), which is thought to be involved in long chain fatty
      acid transport. Nevertheless, long chain fatty acid uptake was not inhibited by
      pretreatment of the cells with an FABPpm antibody, nor by pretreatment with two
      proteases. These data support a saturable component in the transport of long
      chain but not short chain fatty acids by human intestinal epithelial cells, which
      may involve an as yet unknown plasma membrane protein.

PMID- 9026533
TI  - Phase behavior of artificial stratum corneum lipids containing a synthetic pseudo
      ceramide: a study of the function of cholesterol.
AB  - The phase properties and structural characteristics of stratum corneum (SC) lipid
      lamellae have been a subject of considerable interest. To clarify the individual
      role of the stratum corneum constituent lipids, such as ceramides, free fatty
      acids, and cholesterol, we investigated the thermotropic properties and
      aggregation structures of a pseudo-ceramide/stearic acid (1/1 mole ratio)
      cholesterol system, which is a simplified model for the natural lipids.
      Differential scanning calorimetry (DSC) detected decreases of melting entropies
      (delta Sm) by the incorporation of cholesterol into both anhydrous and hydrated
      equimolar mixture of pseudo-ceramide (SLE) and stearic acid. Moreover, there was
      a linear relationship between the cholesterol content and the melting entropies
      in the region of 0-33 mol% cholesterol for both the anhydrous and hydrate lipids.
      In addition, as the concentration of cholesterol increased, a liquid lateral
      packing (4.5 A) appeared in the wide-angle X-ray diffraction and the intensity of
      a hexagonal packing (4.15 A) decreased. The results from the present study
      strongly follow the idea that cholesterol can regulate the mobility of
      hydrocarbon chains of the natural stratum corneum lipid bilayer, which is
      primarily responsible for the barrier properties.

PMID- 9026532
TI  - A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is
      critical for maternal-fetal lipid transport in mice.
AB  - Apolipoprotein (apo) B, the principal structural component necessary for the
      synthesis and secretion of triglyceride-rich lipoproteins by the intestine and
      liver, is highly expressed in the yolk sac visceral endoderm of mammals, although
      its function in this tissue has been hitherto unclear. Disruption of the apoB
      gene in mice results in embryonic lethality (approximately 9.5 - 10.5 d). Here we
      demonstrate that apoB is normally expressed at early time points in embryonic
      development in yolk sac visceral endodermal cells, and that this expression is
      associated with the synthesis and secretion of apoB-containing lipoproteins. The
      lack of apoB in the visceral endoderm resulted in an accumulation of
      intracellular lipid droplets, an absence of lipoproteins from the secretory
      pathway, and reduced concentrations of cholesterol and alpha-tocopherol in
      tissues of apoB-/- embryos. Visceral endoderm of apoB+/- embryos exhibited an
      intermediate phenotype. Our results suggest that apoB plays an essential role in
      the transport of lipid nutrients to the developing mouse embryo via the yolk sac
      mediated synthesis and secretion of apoB-containing lipoproteins.

PMID- 9026534
TI  - Characterization of mutations in the low density lipoprotein (LDL)-receptor gene
      in patients with homozygous familial hypercholesterolemia, and frequency of these
      mutations in FH patients in the United Kingdom.
AB  - Mutations in the gene for the low density lipoprotein (LDL) receptor have been
      identified in 15 patients with homozygous familial hypercholesterolemia (FH).
      Five patients are homozygous at the LDL-receptor locus; their mutant alleles
      include Glu387Lys and Pro664Leu in patients of Asian-Indian descent, Cys292Stop
      in a Greek Cypriot, Cys281Trp in a Turkish patient, and Gln 540Stop in a West
      Indian. The other 10 patients (9 of apparently British ancestry) are compound
      heterozygotes. Mutations have been identified in 18 of 20 possible alleles,
      including Glu80Lys (2 patients), Pro664Leu (3 patients), Asp69Gly, Cys176Arg,
      Cys227Tyr, Ser265Arg, Asp280Ala, Asp283Glu, Arg329Pro, Asp461Asn, Leu578Ser, a
      single bp deletion in exon 15, a 21 bp duplication of codons 200-206 and two
      large deletions. The seven mutations underlined above have not been described
      previously. The two uncharacterized mutant alleles fail to produce detectable
      amounts of mRNA. LDL-receptor activity in cultured cells from 13 of the 15
      homozygous patients varied from undetectable to about 30% of normal, but there
      was no correlation between LDL-receptor activity and the untreated plasma
      cholesterol concentration in these patients. When genomic DNA from 295 patients
      with a clinical diagnosis of FH was screened for 29 mutations found in these and
      other FH patients of British ancestry, most were identified in only one or a few
      individuals. Four patients heterozygous for the Asp461Asn allele showed a wide
      range of clinical manifestations. These observations confirm the striking
      heterogeneity underlying FH in most populations and demonstrate the variability
      in phenotype between patients with the same mutation.

PMID- 9026535
TI  - Acid and enzymatic hydrolysis of the internal sialic acid residue in native and
      chemically modified ganglioside GM1.
AB  - The sialic acid of gangliosides not containing GalNAc (i.e., GM3, GD3) is readily
      hydrolyzed either enzymatically by sialidases or chemically in acid conditions.
      On the other hand, in gangliosides having the sialic acid on the internal
      galactose residue linked to GalNAc (i.e., GM1, GM2) the Neu5Ac is largely
      resistant to acid or enzymatic hydrolysis. In the present work GM1 (NH4+),
      GM1(H+), and several de-acetylated derivatives in the sialic acid and in both
      sialic acid and N-acetylgalactosamine moieties were prepared. Studies by
      counterion exchange with DEAE-Sephadex A-25 and Dowex 50WX8, acid-base titration,
      and acid or enzymatic hydrolysis with sialidases were performed on these
      derivatives. Our results provide cumulative evidence supporting that a hydrogen
      bonding interaction between the hydrogen atom of un-ionized carboxyl group in
      Neu5Ac and the oxygen atom of the carbonyl group in GalNAc reduces the
      dissociation of the Neu5Ac carboxyl group and impairs its enzymatic and acid
      hydrolysis. In addition, our results suggest that the enzymatic hydrolysis of the
      ionized form of sialic acid in GM1(Na+) and GM1(NH4+) is impaired by a second
      hydrogen bonding interaction between the proton of the acetamide group in GalNAc
      and the carbonyl moiety of the carboxyl group of the Neu5Ac.

PMID- 9026537
TI  - ApoA-II kinetics in humans using endogenous labeling with stable isotopes: slower
      turnover of apoA-II compared with the exogenous radiotracer method.
AB  - ApoA-II is a major apolipoprotein constituent of high density lipoproteins (HDL)
      and may play an important role in lipoprotein metabolism and predisposition to
      atherosclerosis. Previous radiotracer kinetic studies have suggested that the
      metabolism of apoA-II in humans may be different than the metabolism of apoA-I,
      the major HDL apolipoprotein. In the present study, we have used an endogenous
      labeling technique using stable isotopically labeled amino acids to study apoA-II
      metabolism and compared the results to those obtained by a simultaneous exogenous
      radiotracer labeling method. Seven subjects with HDL cholesterol levels ranging
      from 9 to 93 mg/dl and apoA-II levels from 13 to 60 mg/dl were investigated in
      this study. [13C6]phenylalanine and 131I-labeled apoA-II were simultaneously
      administered as a primed-constant infusion and a bolus injection, respectively.
      In the endogenous labeling study, plateau tracer/tracee ratios of VLDL apoB-100
      were used as estimates for the precursor pool tracer/tracee ratios for apoA-II
      synthesis. Residence times of apoA-II using these two independent methods were
      found to be highly correlated (r = 0.973, P < 0.0002). These results indicate
      that the endogenous labeling of apoA-II using stable isotopically labeled amino
      acids is a reasonable alternative to the conventional exogenous radiotracer
      labeling method for the investigation of apoA-II turnover. However, under the
      conditions of our experimental design and modeling strategy, the apoA-II
      residence times as determined by endogenous labeling were significantly longer
      (mean 5.33 days) than by exogenous radiotracer (mean 4.65 days). This suggests
      that apoA-II turnover may be even slower than believed based on radiotracer
      studies, and further supports the concept that HDL containing apoA-II are
      metabolized differently than HDL without apoA-II.

PMID- 9026536
TI  - Inhibitors of lipid phosphatidate receptors: N-palmitoyl-serine and N-palmitoyl
      tyrosine phosphoric acids.
AB  - An improved synthesis of two lipid phosphoric acids, N-palmitoyl-L-serine
      phosphoric acid (NP-Ser-PA) and N-palmitoyl-L-tyrosine phosphoric acid (NP-Tyr
      PA), from the benzyl esters of L-serine and L-tyrosine is described. The sequence
      of N-acylation, followed by phosphitylation with N, N-diisopropyl dibenzyl
      phosphoramidite, oxidation to the corresponding phosphate triesters, and
      simultaneous debenzylation of the dibenzyl phosphate and benzyl carboxylic esters
      gave NP-Ser-PA and NP-Tyr-PA in high overall yields. NP-Ser-PA and NP-Tyr-PA and
      their D stereoisomers were potent reversible inhibitors of the lysophosphatidic
      acid receptors expressed in Xenopus oocytes, thus providing prototypic structures
      for the development of inhibitors of the lysophosphatidate family of phospholipid
      growth factors.

PMID- 9026538
TI  - Role of intramolecular disulfide bond formation in the assembly and secretion of
      apolipoprotein B-100-containing lipoproteins.
AB  - Apolipoprotein B-100 (apoB) is essential for the hepatic assembly and secretion
      of triglyceride-rich very low density lipoprotein (VLDL). The mechanism of VLDL
      assembly was explored by perturbing apoB folding in HepG2 cells with the thiol
      reducing agent dithiothreitol (DTT). Although apoB contains eight known disulfide
      bonds, seven of which are positioned in the amino-terminal 21% of the protein,
      its assembly and secretion was only partially blocked in cells treated with 2 mM
      DTT, a condition that fully blocks the secretion of other disulfide-bonded
      proteins. Nonreducing gel electrophoresis of an apoB-derived proteolytic peptide
      revealed that apoB escapes the secretory block normally caused by DTT because its
      amino-terminal disulfide bonds undergo maturation to a DTT-resistant form after
      completing synthesis of only the first approximately 20-25% of the protein. If,
      however, DTT was used under conditions that prevented the initial formation of
      amino-terminal disulfide bonds, lipoprotein secretion was blocked. Reduced forms
      of apoB were extremely labile and, unlike other disulfide-bonded proteins,
      incapable of achieving secretion competence posttranslationally. These results
      indicate that disulfide bond formation within the amino-terminus of apoB is
      essential for the proper folding and assembly of its downstream lipophilic
      sequences. The onset of DTT resistance while still a nascent polypeptide chain is
      consistent with a model in which the amino-terminal domain of apoB undergoes an
      independent folding and maturation process, the completion of which may represent
      an initiation phase of triglyceride-rich lipoprotein assembly.

PMID- 9026539
TI  - Oxidized lipids in the diet are incorporated by the liver into very low density
      lipoprotein in rats.
AB  - Previous studies have shown that the quantity of oxidized lipids in the diet
      directly correlates with the level of oxidized chylomicrons in mesenteric lymph
      and the level of oxidized lipids in endogenous lipoproteins such as very low
      density lipoprotein (VLDL) and low density lipoprotein (LDL). The aim of the
      present study was to determine whether oxidized fatty acids in the diet are
      delivered via chylomicrons to the liver and whether these lipids are repackaged
      and secreted in VLDL. In these experiments, oxidized [14C]linoleic acid was
      utilized as a marker for oxidized dietary fats. When we determined the metabolism
      of nonoxidized and oxidized [14C]linoleic acid-labeled chylomicrons, we found
      that hepatic uptake was similar with 13.57 +/- 0.84% of nonoxidized and 13.40 +/-
      0.96% of oxidized linoleic acid delivered to the liver 30 min after chylomicron
      administration. Additionally, uptake by the extrahepatic tissues was also
      similar. When the hepatic secretion of VLDL was determined in an in vitro
      perfusion system after the administration of nonoxidized and oxidized linoleic
      acid-labeled chylomicrons to intact animals, we found that oxidized linoleic acid
      was utilized for the formation and secretion of VLDL. After the administration of
      labeled nonoxidized and oxidized linoleic acid, 0.86 +/- 0.07% and 0.70 +/- 0.09%
      of the administered label was found in the liver perfusate at 2 h, respectively.
      The presence of oxidized linoleic acid in oxidized VLDL was confirmed by
      demonstrating the presence of hydroperoxide-derived hydroxy octadecanoic acid.
      Thus, our findings demonstrate that oxidized dietary lipids are delivered to the
      liver via chylomicrons where they are utilized for synthesis of endogenous
      lipoproteins such as VLDL.

PMID- 9026540
TI  - Validation of [22,23-3H]cholic acid as a stable tracer through conversion to
      deoxycholic acid in human subjects.
AB  - Bile acids labeled with 3H on the sterol nucleus lose a substantial fraction of
      label during enterohepatic cycling and conversion to secondary bile acids. We
      tested the isotopic stability of a side-chain 3H label, [22,23-3H]cholic acid in
      humans. The 3H-labeled compound was administered simultaneously with [24
      14C]cholic acid to four healthy volunteers. Duodenal bile was collected daily for
      5 days after isotope administration to determine the ratio of 3H/14C in bile
      acids. Urine was collected to determine loss of radioactivity by this route.
      Cholic acid and deoxycholic acid were isolated from biliary bile acids by thin
      layer chromatography after deconjugation with cholylglycine hydrolase. The ratio
      of 3H/14C in cholic acid and deoxycholic acid remained constant and identical to
      that of the administered mixture in all subjects, indicating stability of the 3H
      label during enterohepatic cycling. Cumulative loss of 3H in urine averaged only
      1.2% of administered dose and was identical to loss of 14C (average 1.3%)
      indicating little if any transfer of 3H from bile acid to body water.
      Deconjugation of biliary bile acids by alkaline hydrolysis resulted in 15-20%
      loss of 3H label, consistent with known base-catalyzed exchange of alpha-carbon
      protons on carboxylic acids. We conclude that [22,23-3H]cholic acid is a
      biologically stable, and therefore reliable, isotopic tracer of cholic acid in
      humans during enterohepatic cycling including conversion to deoxycholic acid,
      provided deconjugation is performed enzymatically. Because the 22,23-3H label can
      be inserted into most C24 bile acids, it appears the best way to tag 3H-labeled
      bile acids for metabolic studies.

PMID- 9026541
TI  - [Cardiac evaluation in arteritis].
AB  - Coronary artery disease is very frequent and responsible for half of the death in
      patients with peripheral arterial disease. Clinical and electrocardiographic
      cardiac check-up must be systematic. The choice of coronary investigations must
      be guided by the clinical context. Exercise stress testing, with upper limb if
      necessary, must be performed in patients with suspected coronary artery disease
      and before high risk surgery. Dobutamine echocardiography or dipyridamole
      myocardial scintigraphy are justified in patients unable to performed a
      satisfactory exercise stress testing. Coronary angiography must be limited to
      patients with angina and/or recent myocardial infarction, and to patients with
      known coronary artery disease and high risk surgery.

PMID- 9026542
TI  - [CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy)].
AB  - Recently identified, CADASIL is a diffuse disease of small arteries,
      predominating in the brain. It starts during mid-adulthood and is characterized
      by recurrent ischemic events (transient or permanent), attacks of migraine with
      aura, severe mood disorders, subcortical dementia and, at MRI, a white spread
      leukoencephalopathy. There is so far no specific treatment and death occurs after
      a mean of twenty years. CADASIL is an autosomal dominant condition and the gene
      Notch 3 is located on chromosome 19, in the same region as another neurological
      disorder, familial hemiplegic migraine.

PMID- 9026543
TI  - [Lymphoscintigraphic aspects of the effects of manual lymphatic drainage].
AB  - Manual lymphatic drainage is used in physiotherapy of limb lymphedema in
      combination with other physical techniques. In order to assess the effectiveness
      of the method, 47 patients with upper limb lymphedema after radiosurgical therapy
      for breast cancer underwent lymphoscintigraphy. The examination was performed
      after subcutaneous injection of technetium-labeled colloid via the fourth and
      first interdigital space on the hand of the limb with lymphedema. The level of
      the technetium label was compared on scintigraphies performed before and after
      manual lymph drainage. Results were analyzed as a function of the clinical
      characteristics of the edema. Manual lymphatic drainage produced an effective
      progression of the label in 25 cases (53.2%), independent of radiotherapy.
      Contralateral lymph nodes were reached in 5 cases and the homolateral internal
      mammary nodes in 2. These nodes were visualized only after manual lymphatic
      drainage. The visualization of the drainage routes in unexpected areas
      demonstrated the effectiveness of the technique in stimulating accessory routes
      useful for resorption of lymphedema. The use of two injection sites on the hand
      is also discussed. This study demonstrated the effect on a single session of
      manual lymphatic drainage and should be completed with an assessment of a
      complete series of manual lymphatic drainages.

PMID- 9026544
TI  - [Short-term change in sural venous thrombosis in patients in surgical intensive
      care when anticoagulants are contraindicated].
AB  - Venous thrombo-embolic disease in neurosurgical and surgical intensive care units
      is a frequent disorder (between 4.3 and 43 per cent of patients according to
      studies). The treatment is often difficult. We carried out a retrospective study
      from January 1994 to September 1995 of 57 patients in neurosurgical and surgical
      intensive care who developed thrombosis of a sural vein and in whom anticoagulant
      at therapeutic doses was contraindicated. After a median follow up 14 days
      echography showed proximal extension of the thrombosis in 4 patients and distal
      extension in 3 others. Five cases of pulmonary embolism occurred during the
      follow up period, one of which led to death. No complications (pulmonary embolism
      or proximal extension of venous thrombosis) occurred in those patients receiving
      heparin at prophylactic doses (0/11 versus 8/46 in the non-heparin group; p =
      0.13). No case of pulmonary embolus occurred in those patients with partial or
      complete regression of the thrombosis (0/21 versus 5/36 in the group with stable
      or extending thrombi, p = 0,05). Echographic monitoring enabled therapeutic
      modification in 5 cases. These results indicate that sural venous thrombosis in
      the context of neurosurgical and surgical intensive care is a potentially grave
      situation and that the prescription of anticoagulant therapy even at preventive
      dose should always be considered. Further, we propose regular echographic
      monitoring until the patient is mobile.

PMID- 9026545
TI  - [Laser-Doppler flowmetry and arterial diseases of the limbs. Correlations with
      measurement of transcutaneous oxygen pressure].
AB  - The place of laser-Doppler flowmetry is not well established among the other
      techniques of evaluation of local microcirculatory blood flow. We conducted a
      study in 15 controls (mean age 49.5 yrs, 30 limbs) and 37 patients with
      peripheral arterial occlusive disease (PAOD) (mean age 59.1 yrs, 67 limbs, 50
      mild ischemia and 17 severe ischemia) and assessed the local blood flow with
      laser-Doppler (Perimed PF3) and transcutaneous oximetry (Hellige Oxymonitor);
      both probes being heated at 44 degrees C. Transcutaneous oxygen tension (TcpO2
      mmHg) and laser-Doppler fluxes (LDF in perfusion units PU) were measured at the
      foot dorsum in resting horizontal supine position and leg dependency (30
      controls, 67 PAOD) and during post-ischemic reactive hyperemia (36 PAOD). The
      results (mean +/- sd) were compared within each group (controls, mild ischemia,
      severe ischemia) by means of a paired t-test, between the different groups by a
      variance analysis and correlations by a Spearman test. LDF decreased from supine
      position to leg dependency in the control group (24.1 +/- 22.2 PU horizontal vs
      19.0 +/- 26.2 dependent, N = 30, p < .05) but not in the PAOD group (mild
      ischemia respectively 46.0 +/- 41 vs 42.9 +/- 35 PU, N = 50; severe ischemia 41.3
      +/- 27 vs 48.6 +/- 42 PU, N = 17). LDF was significantly higher at rest: mild
      ischemia 46 +/- 41 (N = 50), severe ischemia 41.3 +/- 27 (N = 17) vs controls
      24.1 +/- 22 PU (p < .005). LDF increased during hyperemia in controls (peak flux
      42.4 +/- 28.9 PU, p < .00001) and in patients with mild ischemia (46.0 +/- 42 vs
      32.5 +/- 39 PU at rest, N = 29, p < .005) but not in severe ischemia (29.4 +/- 18
      vs 28.7 +/- 33 PU at rest, N = 7). TcpO2 at rest (65.9 +/- 14 mmHg in 30
      controls) decreased significantly in mild ischemia (55.6 +/- 16 mmHg, N = 48) and
      severe ischemia (32.1 +/- 26 mmHg, N = 17, p < .005). On leg dependency, TcpO2
      increased in mild ischemia (70.2 +/- 13 leg dependent vs 52.6 +/- 12 mmHg
      horizontal, N = 21, p < .001) and severe ischemia (respectively 35.6 +/- 24 and
      26.1 +/- 15 mmHg, N = 10, p < .01). No correlations were found between LDF
      parameters and TcpO2 except in patients with severe ischemia (LDF horizontal and
      dependent with TcpO2 dependent).

PMID- 9026546
TI  - [The Laser-Doppler microcirculation technique in the study of the
      orthosympathetic system in obese and non-insulin-dependent diabetic patients].
AB  - Parasympathetic as well as cardiovascular sympathetic activity is perturbed in
      the heart of diabetic and obese subjects. The aim of this work was to assess the
      effect of sympathetic control on variations in skin blood flow in 14 controls, 42
      subjects with non-insulin-dependent diabetes and 57 obese subjects without
      diabetes. All subjects had normal blood pressure and had no other disease state
      which might modify skin blood flow. Laser-Doppler measurement of skin blood flow
      on the palmar aspect of the right first finger was performed at rest and during
      three tests which activate sympathetic tone: deep respiration (R), active
      orthostatism (O) and Valsalva's manoeuvre (V). In all 113 subjects, there was a
      negative correlation between age and the standard deviation of blood skin flow at
      rest (p = 0.001) and rate of blood skin flow decline during R (p = 0.002), O (p <
      0.0001) and V (p = 0.005). The standard deviation and slope of decline in blood
      skin flow during R was lower than the initial levels in controls in 11 diabetes
      patients and 6 obese subjects and in 15 diabetic patients and 12 obese subjects
      respectively. The slope of decline in skin blood flow during O was positively
      correlated with plasma cholesterol (p = 0.002), red cell aggregation index (p =
      0.013) and negatively with hematocrit, glucose control and creatininemia. The
      respective effects of these factors were analyzed in each of the three groups of
      subjects. These preliminary results suggest that 1) the variation in skin blood
      flow at rest is regulated by the sympathetic system and the drop in skin blood
      flow during the three tests activating the sympathetic system decreases with age,
      2) sympathetic control of peripheral vasoconstriction is reduced in many diabetic
      and obese subjects, 3) red cell aggregability and different metabolic parameters
      and renal function have an effect.

PMID- 9026547
TI  - [Non-cardiac causes of acute ischemia in the arms].
AB  - Among a series of 286 cases of acute ischemia of the upper limb, we analyzed the
      files of 176 patients (61.5%) with noncardiac ischemia in order to identify the
      causes and treatment. Trauma was the most frequent cause (126 cases) including
      trauma of the forearm especially due to stab wounds. Lesions with a subclavian
      axillary localization were predominantly due to tear wounds or blunt trauma. We
      analyzed two groups among the trauma cases: iatrogenic lesions (9 cases) usually
      resulted from orthopedic surgery (5 cases) or vascular catheterization (3 cases)
      as well as near-total limb amputations (13) cases. Thrombosis of the subclavian
      artery occurred in 33 patients; 9 had acute ischemia including 3 due to a
      cervical rib and 6 due to compression by the rib and the clavicle. Only 4 of
      these 33 patients suffered ischemia of the hand due to embolization. Acute
      ischemia was caused by arteriopathy of the hand in 8 patients including 2 volley
      ball players, 1 baseball player and 3 subjects with occupational microtrauma and
      1 with thrombosis of the palmar arch. Finally 1 patient had thrombosis after
      intravenous drug injection. These files demonstrated the variety of non-cardiac
      causes of acute ischemia of the upper limb. During the acute phase, we propose
      locoregional thrombolysis in case of thrombosis and embolectomy for emboli
      followed by treatment of the casual lesion. An arteriography is essential for
      correct diagnosis and should include the subclavian artery in the hyperabduction
      position and the hand. Duplex scanning of the subclavian artery is indicated in
      case of ischemia of the hand using the Adson, McGowan and Wright maneuvers in
      order to guide the radiologist for invasive radiography before initiating
      appropriate treatment.

PMID- 9026549
TI  - [Non-deployment of branches of a vena cava filter. Elements of prevention].
AB  - Non-deployment of an L.G.M. percutaneous vena cava filter is rare. The aim of
      this paper is to report a new case of this complication. A second filter was
      inserted between the non-deployed filter and the renal veins to prevent proximal
      migration of the transvenous interruption device to the pulmonary artery or the
      right side of the heart, and to guarantee an effective prophylaxis of further
      pulmonary embolization. Two years later, the vena cava was still patent. The best
      way to avoid this accident is a perfect insertion technique: after a preoperative
      cavography to check diameter and patency of the vena cava, the filter must be
      deployed by retracting the introducer sheath while maintaining the position of
      the inner canula, and not pushing the filter out of the introducer sheath. A
      second filter must always be available in the operating room in case of
      incomplete opening of the filter. The use of vena cava filter is not devoid of
      risks. Restricted indications are therefore recommended.

PMID- 9026548
TI  - [Carotid-jugular fistula after an attempt at placement of a vena cava filter].
AB  - A carotid-jugular fistula complicated the placement of a Green-field filter via
      the right internal jugular percutaneous passage: the local signs of an arterio
      venous fistula were associated with right parietal infarction neurological
      symptoms. A crossography showed a carotid-jugular fistula and a limited
      dissection of the original carotid artery. An elective echo-guided compression
      failed. The surgical treatment eliminated the fistula, fixed the carotid
      dissection and placed a vena cava filter with an excellent result 34 months
      later. Percutaneous placement of vena cava filters can lead to rare vascular
      complications such as carotid-jugular fistulas which can, in certain cases, be
      treated with an elective external compression or endovascular procedures. Surgery
      offers a reliable technical solution that is complete and stable in time,
      particularly with recent fistulas and associated neurological symptoms.

PMID- 9026550
TI  - [Branchial paraganglioma. A case of carotid paraganglioma and review of the
      literature].
AB  - We report the case of a 58-year-old man hospitalized for generalized seizures. A
      grade II glioma of the left frontotemporal region was diagnosed on brain CT scan
      and stereotaxic biopsy results. Radiotherapy was successful in treating this
      glioma. A glomus tumor of the left carotid was discovered by duplex Doppler
      examination of the carotid and confirmed on arteriography. Resection was
      performed to the adventitia. Branchial glomus tumors are rare, often benign
      tumors. The carotid is a common localization. Surgery is often indicated due to
      the risk of local invasion. Surgical procedure varies according to the size and
      localization of the tumor. This case demonstrates that glomus tumor of the
      carotid can coexist with a frontotemporal glioma.

PMID- 9026551
TI  - [Manipulations of cervical vertebrae and trauma of the vertebral artery. Report
      of two cases].
AB  - Vertebrobasilar-distribution stroke is a rare but sometimes severe complication
      of chiropractic neck manipulation. We report two patients with dissections of the
      vertebral arteries authenticated two and six days after the cervical
      manipulation. In the first case, a Wallenberg's syndrome occurred due to a
      dissection of the right intracranial vertebral artery; the patient was treated
      with anticoagulant therapy but little improvement of the disorder was noted. The
      second patient had transitory neurologic manifestations which led to the
      discovery of an intimal tear of the ostium of the right vertebral artery with a
      floating clot. Further embolic complications were avoided by performing a venous
      bypass between the right common carotid and the vertebral artery at the base of
      the skull. Therapists should be aware of vertebrobasilar complications after
      spinal manipulations and should ask for early explorations (brain CT, cerebral
      angiography) to institute rapidly the most appropriate treatment.

PMID- 9026552
TI  - [Acquired autoantibodies against human factor VIII: a new case].
AB  - The finding of a prolonged partial thromboplastin time and a normal prothrombin
      time localized the coagulation defect to the intrinsic or contact activation limb
      of the coagulation cascade. Because the situation is a source of hemorrhage, a
      rational and rapid approach is necessary with measure of factors of intrinsic
      limb of coagulation (especially factors VIII and IX, for the diagnosis of classic
      hemophilia), study of von Willebrand factor and search of coagulation factor
      inhibitors. We report the case of a 25-year old woman with high titer postpartum
      antibody against factor VIII for illustrating the diagnosis approach.

PMID- 9026553
TI  - [Paresthesia, pain, coldness of the arm and possible responsibility of the
      thoraco-brachial outlet syndrome].
AB  - Paresthesia, pain and coldness of the upper limb strongly suggest ischemia. The
      questions raised concern the etiology and treatment. 1) Treatment is based on
      confirmation of the unilateral nature of the disorder requiring search for the a
      locoregional cause (examination of the subclavian outlet) and on elimination of a
      cardiac or general origin. Two noninvasive examinations are indicated. An X-ray
      examination of the upper chest bones is performed to search for an abnormal
      formation, usually a cervical rib. Presence of a cervical rib indicates a
      possible damage to the sub-clavian artery in the thoraco-brachial outlet and,
      inversely, absence of a cervical rib suggests either arterial damage or a
      fibromuscular cause. Ischemia of the upper limb results from repeated microtrauma
      to the sub-clavian artery due to a bone-ligament anomaly resulting in thickening
      and parietal ulceration, and sometimes post-stenosis embolism or in situ
      thrombosis. Duplex Doppler may be able to identify the nature of the cause
      without dynamic manoeuvres. An arteriography is essential to confirm the level of
      the obstacle, its nature, the status of the downstream bed and possible
      relationship between a bone anomaly and the sub-clavian artery. Several
      incidences may be required. 2) Therapeutic modalities must take into account the
      ischemia and its cause. Surgery is required to remove the obstacle and repair the
      arterial damage, and possibly to remove an embolus. It is relatively easy to
      remove a cervical rib or repair a bone muscle anomaly, allowing arterial repair
      with or without venous bypass. Embolectomy of an earlier embolus may require
      major reconstruction vascular surgery.

PMID- 9026554
TI  - Some additional results about polymorphisms in models of an additive quantitative
      trait under stabilizing selection.
AB  - The existence of two stable, symmetric (allelic frequency 0.5 in each locus)
      polymorphic states is demonstrated for a two-locus model of an additive
      quantitative trait under strong Gaussian selection. Linkage disequilibrium at one
      of the states is negative whereas it is positive at the other state. For a three
      locus model, it is shown that in order to maintain a stable polymorphism in all
      three loci, selection must be sufficiently but not excessively strong relative to
      recombination. Also, positive linkage disequilibrium can be maintained in a three
      locus model under stabilizing selection that is not very strong.

PMID- 9026555
TI  - The birth.

PMID- 9026556
TI  - Drug interactions program.

PMID- 9026557
TI  - Clinical Significance of a cervical cytologic diagnosis of atypical squamous
      cells of undetermined significance. Favoring a reactive process or low grade
      squamous intraepithelial lesion.
AB  - OBJECTIVE: To define the clinical significance of qualifying the cytologic
      diagnosis of atypical squamous cells of undetermined significance (ASCUS) as
      favoring either a reactive process or a low grade squamous intraepithelial lesion
      (LSIL) in an effort to provide management guidelines. STUDY DESIGN: A total of
      118 consecutive nonpregnant women with a cytological diagnosis of ASCUS favoring
      either a reactive process or LSIL were evaluated in our colposcopy clinic by
      repeat cervical cytologic smear, colposcopy and colposcopically directed biopsies
      and/or endocervical curettage, as indicated. RESULTS: Of the 58 patients
      evaluated for a smear of ASCUS, favoring a reactive process, 5 (8.6%) had
      cervical intraepithelial neoplasia (CIN) CIN 1 documented by biopsy. None had a
      high grade lesion. Twenty-six (45%) of the 58 patients who had a cytologic
      diagnosis of ASCUS favoring a reactive process had a repeat smear that was
      normal. None was found to have CIN. Of the 60 patients who had a cervical
      diagnosis of ASCUS favoring LSIL, 9 (15%) had CIN 1 or CIN 2. Nineteen (32%) of
      the 60 patients who had a cytologic diagnosis of ASCUS favoring LSIL had a repeat
      smear that was normal. One of these patients had CIN 1 on biopsy. The sensitivity
      of a repeat smear, in this limited series, after an initial smear of ASCUS
      favoring a reactive process is 100%, while it was 66% after an initial smear of
      ASCUS favoring LSIL. CONCLUSION: This study showed that in our laboratory a
      cytologic diagnosis of ASCUS favoring either a reactive process or LSIL is
      associated with a very low risk that the patient is haboring CIN. In the patient
      whose initial smear shows ASCUS favoring a reactive process, a repeat smear that
      is normal is reassuring. The patient whose smear shows ASCUS favoring LSIL
      probably requires further evaluation even in the presence of a normal repeat
      smear.

PMID- 9026558
TI  - [Mechanical ileus of the small intestine--its surgical treatment and
      complications].

PMID- 9026559
TI  - [Bulgarian Surgical Society. Minutes. Bylaws].

PMID- 9026560
TI  - [Diprivan anesthesia in a case with intraoperative corticography].

PMID- 9026561
TI  - [A case of tetanus (facial form) following combined trauma].

PMID- 9026562
TI  - [A case of an omental cyst].

PMID- 9026563
TI  - [Serotonin in diabetic retinopathy].
AB  - PURPOSE: The present study was designed to evaluate a possible participation of
      serotonin in the development of retinopathy in diabetes mellitus. MATERIAL AND
      METHODS: Serotonin of whole blood and platelets was studied in 12 patients with
      Type I and II diabetes using high pressure liquid chromatography method. RESULTS:
      The concentration of serotonin in the blood was markedly increased (210 +/- 50
      ng/ml in diabetes and 150 +/- 35 ng/ml in control, p < 0.01) and not changed in
      platelets in diabetes. There was a relation between blood serotonin level and the
      presence of retinopathy. CONCLUSION: These results suggest that serotonin may be
      involved in the pathogenesis of diabetic microangiopathy.

PMID- 9026564
TI  - [Evaluation of blood flow rate in the internal carotid system in various types of
      retinal vein occlusion].
AB  - The aim of the study was to evaluate blood flow rate by means of Doppler
      pulsating ultrasonography focused in internal carotid artery, opthalmic artery
      and posterior ciliary arteries in patients with different types of retinal veins
      occlusion. The material included 8 patients with congestive venous retinopathy,
      27 with ischaemic central retinal vein occlusion and 35 with central retinal vein
      branch occlusion. The flow measurements were performed using ultrasound 3-D trans
      Scan of EME company. RESULTS: Patients with ischaemic occlusion revealed
      statistically significant decrease of blood flow rate in opthalmic artery and
      posterior ciliary arteries on the ill eye side. Moreover, these patients had the
      worst course of the disease, including permanent sight defect, ischaemic
      complications in the funds of the eye and in fluorescein angiography. Flow
      measurements confirmed the role of arterial flow insufficiency in formation and
      clinical course of retinal vein occlusion and in development of complications.

PMID- 9026565
TI  - [Evaluation of the general condition and selected biochemical blood parameters in
      various types of retinal vein occlusion].
AB  - The aim of the study was to evaluate the coagulant and fibrinolytic system, lipid
      economy and neurological condition in patients with various types of retinal vein
      occlusion. The material was 70 patients: 8 with diagnosed congestive venous
      retinopathy, 27 with ischaemic central retinal vein occlusion and 35 with central
      retinal vein branch occlusion. Apart from the neurological evaluation, every
      patient underwent determination of: hematocrit, number of blood platelets, total
      plasma protein with its electrophoretic division, plasma fibrinogen level, kaolin
      cephalin and prothrombin coefficient, and the level of triglycerides, total
      cholesterol with its fractions LDL and HDL. RESULTS: Considerable percentage of
      patients with arterial hypertension and suffering from partial or multi
      symptomatic hemiparesis associated with complication in plasma lipid content
      indicates significant atheromatous changes in vascular wall which promote
      occlusion formation. The role of rheological factors in pathogenesis of these
      changes seems to be secondary.

PMID- 9026566
TI  - [Clinical course and complications of different retinal occlusion types based on
      personal material].
AB  - The aim of the study was to analyse the clinical course and frequency of
      complications depending on type of retinal vein occlusion. The material included
      70 patients (27 men, 43 women) aged 60.3 +/- 10.5 years. Follow-up period was 3
      to 36 months from the occurrence of first clinical symptoms. Case history
      included occurrence of common diseases predisposing to occlusion formation, use
      of drugs and type of predromal symptoms. Full ophthalmologic examination was
      performed at the start and the end of follow-up. Visual field was measured with
      TOPCON statistic perimeter SPB 2020. Fluorescein angiography was done in 45
      patients. RESULTS: 8 patients appeared to have congestive retinography, 27
      ischaemic retinal vein occlusion and 35-central retinal vein branch occlusion.
      Prodromal symptoms were mainly short-term (few minutes) eye blindness. Both the
      evaluation of sight organ function and ophthalmoscopy indicated more severe
      course of ischaemic occlusion in comparison with congestive occlusion. Absence of
      retinal capillary perfusion was observed only in cases of ischaemic occlusion.

PMID- 9026567
TI  - [Intraocular implants in the posterior chamber after intraoperative posterior
      capsule tear].
AB  - PURPOSE: To present the results of cataract surgery with IOLs implantation
      complicated by posterior capsule tear. MATERIAL AND METHODS: 38 eyes of 38
      patients with cataract, operated on between August 1993 and May 1994 were
      examined. In all cases posterior capsule tear occurred during surgery but the
      IOLs were supported by the residual capsule or, when the tear was large, by the
      residue of the anterior capsule with haptics being placed in the ciliary sulcus.
      RESULTS: Useful visual acuity was achieved in 78% of the eyes. The main
      complications observed in post-operative period were increase of intraocular
      pressure in 11 eyes, dislocation of IOL in 4 and dyscoria in 24 eyes. CONCLUSION:
      The applied surgical technique seems to be very useful in cases of posterior
      capsule tear but in each case the surgeon must decide what is the best for the
      eye: anterior or posterior chamber IOL.

PMID- 9026568
TI  - [Results of surgery after intraocular disc lens implantation].
AB  - PURPOSE: To evaluate the results of Medi Contur IOLs implantation, which are a
      slightly modified Galand disc lens. MATERIAL AND METHODS: In the years 1994-1995,
      31 eyes were operated on using modified method with horizontal, linear anterior
      capsule incision and intercapsular disc lens implantation. The follow-up was 6
      months. RESULTS: Mean visual acuity was 0.7-0.8. There were no complications
      different from those occurring in other types of IOLs. The residual anterior
      capsule has no negative influence on visual acuity. The shape, size and
      localization of the IOL in physiological place, between anterior and posterior
      capsule, cause the good position and stability of the lens. The risk of
      development of the posterior capsule folds and opacity was decreased on account
      of a uniform capsular tension and contact of the IOL with the posterior capsule.
      CONCLUSION: The presented method of cataract extraction and IOL implantation,
      with all manipulations in intercapsular space is safer in comparison with others
      methods and residual anterior capsule decreases the risk of lens dislocation.

PMID- 9026569
TI  - [The value of bacteriologic examination in cataract surgery].
AB  - The purpose of our study was to compare the incidence of intrabulbar infections
      following cataract extraction and its correlation with the results of
      preoperative bacterial cultures. We examined 2344 patients who were operated on
      from 1st January 1993 to 31st December 1994 in our hospital. Patients were
      divided into 3 groups. In the first group surgery, was performed only in cases
      where preoperative cultures were negative, in the second group conjunctival
      cultures were prepared just before surgery. In the third group no preoperative
      cultures were prepared. Additionally in the second and the third group one drop
      of 5% Betadine solution was administered to the conjunctival sack just before
      surgery. We conclude that negative preoperative conjunctival cultures did not
      prevent from postoperative infections of the eye. After resigning of preoperative
      bacterial cultures the incidence of intrabulbar infections following cataract
      surgery did not increase in our study.

PMID- 9026570
TI  - [Severe myopia and delivery].
AB  - AIM: There has been concern that patients with high myopia are at a risk of
      developing retinal tears as they go through a spontaneous delivery. Therefore the
      aim of the paper was to examine retinal changes in the group of female patients
      with high myopia before and after delivery. MATERIAL AND METHODS: Eye
      examinations were performed before and after delivery in two groups of patients:
      42 patients with high myopia and 4 patients with high myopia and retinal
      detachment surgery in one eye. RESULTS: There was no progression of retinal
      changes and development of retinal tears, but in some patients retinal
      hemorrhages and macular edema were observed. CONCLUSIONS: High myopia is not the
      indication for the cesarean section, but the patients should be examined after
      the delivery.

PMID- 9026571
TI  - [Vitrectomy in Terson's Syndrome].
AB  - AIM OF THE STUDY: The authors present results of vitrectomy in the treatment of a
      50 year old woman with Terson's Syndrome. MATERIAL: Pars plana vitrectomy was
      performed in two eyes of a 50 year old woman with vitreous hemorrhage caused by
      the rupture of cerebral arteries aneurysms. The vitreous hemorrhage occurred two
      days after the neurosurgery procedure. Visual acuity in both eyes was hand
      movement and did not change after pharmacotherapy and cryotherapy. Pars plana
      vitrectomy was performed in the right eye 3, 5 months after the hemorrhage and in
      the left eye 5 months after the hemorrhage. Visual acuity 5/12 in the right eye
      and 5/7 in the left eye was achieved after the vitrectomy and 5/50 (the decrease
      caused by cataract) and 5/7 after 11 and 7 months of follow-up. CONCLUSION: Pars
      plana vitrectomy is a method of choice in the cases of binocular Terson's
      Syndrome and accelerates returning of useful visual acuity.

PMID- 9026572
TI  - [Necrotizing scleritis--case report of a patient effectively treated with high
      doses of corticosteroids].
AB  - A case of a patient with necrotizing scleritis of both eyes who had been under
      medical observation and who had undergone medical treatment for five years is
      described. During the first manifestation of his disease in spite of medical
      treatment the right eyeball ruptured and was removed. After four years scleritis
      in the left eye started. An intensive pulsating steroid therapy was used due to
      which the remission of this disease was obtained. This method of treatment of
      necrotizing scleritis with unknown etiology seems to be the most efficient.

PMID- 9026573
TI  - [Changes in the anterior segment of the eyeball as the first symptom of carotid
      artery occlusion].
AB  - A case of a woman with neovascularization of the iris in the anterior segment of
      the right eye and symptoms of secondary glaucoma has been described. During the
      third day of her hospitalization the symptoms of the embolus of the central
      retinal artery appeared. The examination of her carotid arteries by means of
      Doppler's ultrasonography was used. The ultrasonography showed the occlusion of
      the internal carotid artery and the external one on the left side and the
      stenosis of the common carotid artery and the right internal one due to numerous
      thrombi. The patient was advised to have her carotid arteries operated on but she
      did not agree on the surgery. Now the right eye is blind. The non-invasive method
      of Doppler's ultrasonography enables a quicker diagnosis and gives efficient
      medical treatment before serious complications occur.

PMID- 9026574
TI  - [Antioxidants for prophylaxis of eye diseases].
AB  - The contemporary literature has widely described the role of free oxygen radicals
      and their antioxidants in pathogenesis of some eye diseases, mainly cataract, age
      related macular degeneration, retinopathy of prematurity and cystic macular
      oedema. This paper presents publications which stress the importance of
      antioxidants use in prophylaxis of cataract and age-related macular degeneration.
      Positive antioxidants role was proved both in experimental research and in
      clinical observations.

PMID- 9026575
TI  - [Reactive oxygen forms in pathogenesis of selected eye diseases].
AB  - The paper presents mechanisms by which reactive oxygen forms appear in the
      eyeball and their effects on the tissues. They play an important role in
      pathogenesis of many eye diseases, especially in cataract, age-related macular
      degeneration and retinopathy of prematurity.

PMID- 9026576
TI  - [Serotonin--its significance in physiology and pathology of the eye].
AB  - In this review the basic data concerning metabolism of serotonin, its receptors
      and effects are presented. The authors have underlined the significance of
      serotonin in the physiology and pathology of the eye with special regards to the
      effectiveness of serotonergic system affecting drugs in the disturbances of
      vision process.

PMID- 9026578
TI  - [Ophthalmologic treatment in Saxon times].

PMID- 9026577
TI  - [Contemporary views on the etiopathogenesis of thrombotic changes in the retinal
      vein].
AB  - The authors emphasize the complex and multifactorial mechanism by which retinal
      vein occlusion occurs. A special attention is paid to arterial insufficiency
      which impacts formation of clinical picture as well as the development of
      occlusion and the complications.

PMID- 9026579
TI  - [Studies of changes in filtration angle after experimental administration of
      ethacrynic acid into the anterior chamber].
AB  - The aim of the study is to determine what charges occur in filtration angle after
      administration of ethacrynic acid solution into anterior chamber. The study was
      conducted in 9 rabbits. After administration of 0.5 mmol/l and 0.7 mmol/l
      epsilon. acid solution, oedema of cells, relaxation of structure of trabecular
      texture and cellular necrobiosis in filtration angle were detected. Intraocular
      pressure lowered by 6-7 mm Hg. It is possible that ethacrynic acid will be used
      as an agent inducing changes in filtration angle which reduce intraocular
      pressure.

PMID- 9026580
TI  - [Level of uric acid in aqueous and vitreous humor of man].
AB  - Uric acid-a potent endogenous antioxidant-may play a certain role in some eye
      diseases. However, its content in intraocular humors has not been examined so
      far. Samples of aqueous and vitreous humor were collected from 32 dead persons
      for examination. Uric acid was marked by indirect method with uricase. Uric acid
      level in aqueous humor ranges from 166.67 to 446.4 mumol/l (mean 309.34), whereas
      in vitreous humor from 77.38 to 452.00 mumol/l (mean 220.80).

PMID- 9026581
TI  - [Level of uric acid in aqueous humor of patients with cataract].
AB  - Aqueous humor was taken from 32 patients with senile and presenile cataract at
      the operation by means of anterior chamber puncture. Uric acid was marked by
      indirect method with uricase. The mean content of uric acid in aqueous humor of
      patients with cataract was 187.13 mumol/l and in the control group 309.34
      mumol/l. The difference between the groups is statistically significant. The
      results suggest that uric acid as strong endogenous antioxidant may play an
      important role in pathogenesis of cataract.

PMID- 9026582
TI  - Developing educational materials for patients.

PMID- 9026583
TI  - [Diagnostic approach in coronary disease in developing countries].

PMID- 9026584
TI  - [A yellow fever liver].

PMID- 9026585
TI  - [Vanuatu: recent aspects of an ex-condominium].

PMID- 9026587
TI  - [Lice, fleas, ticks and ants: non-venomous apterous arthropods].

PMID- 9026586
TI  - [Kaposi sarcoma and human herpes virus type 8: recent data].

PMID- 9026588
TI  - [Management of chronic anemia in the adult in tropical zones].

PMID- 9026589
TI  - [Emerging agents and microbiological laboratory security].

PMID- 9026590
TI  - [Should tropical medicine be taught in France?].

PMID- 9026591
TI  - [Pathologies associated with HTLV-1 virus in Dakar (1992-1995)].
AB  - A clinical and laboratory study was conducted in Dakar (Senegal) to assess the
      involvement of HTLV-1 virus (human T lymphotrophic virus type 1) in various
      diseases. Patients were enrolled at three locations: the Dermatology Department
      of the Fann University Hospital Center (845 patients) from 1992 to 1995, the
      Dermatology Department of the Le Dantec University Hospital Center and the
      Oncology Department of the Principal Hospital (7 patients) in 1994 and 1995. The
      incidence of involvement of human retroviruses in neurologic complications seemed
      low (HTLV-1: 2%, HIV: 3%) and only 6 cases of tropical spastic paraparesis
      associated with specific anti-HTLV-1 antibodies were diagnosed in 3 men and 3
      women with a mean age of 51 years. These cases which were identical to those
      previously described cases in the West Indies and Japan confirms the existence of
      this disease in Senegal. In addition 3 cases of isolated facial paralysis were
      observed in HIV positive patients. Combined HIV/HTLV-1 infection was observed in
      3 cases and was not associated with special clinical findings. Adult T-cell
      leukemia/lymphoma (ATL) was detected in 4 patients including leukemia with
      proliferation of CD4 and CD25 in two cases and lymphoma in one case. In one case
      of ATL two proviruses were identified in circulating tumor cells. These are the
      first cases of ATL to be reported in Senegal. Molecular characterization of part
      of the envelope gene (gp 21) from patients with PST hospitalized in a neurology
      ward showed that the virus present in Senegal belonged to the universal HTLV-1 A
      type. This study indicates that two types of diseases are associated with HTLV-1
      infection in Senegal. Further epidemiologic studies will be needed to evaluate
      the incidence of the virus and of the diseases associated with it. Prevention
      will depend partly on screening blood donors as has now been started at the Blood
      Transfusion Center of Dakar.

PMID- 9026592
TI  - [Hepatitis A virus immune status of Antilles military personnel: incidence after
      prophylaxis].
AB  - The purpose of this study was to ascertain the value of systematic vaccination of
      recruits from French overseas departments and territories (DOM-TOM) against
      hepatitis A. Between July 1994 and May 1995 tests to defect anti-HVA antibodies
      were performed on all new recruits from the French West Indies (Guadeloupe and
      Martinique). Of the 1685 subjects tested 346 presented type IgG anti-HVA
      antibodies, i.e. 20.5% overall. Seroprevalence increased from 4% in 18 year-olds
      to 35% in 25 year-olds and was significantly higher in recruits from Gaudeloupe
      (26.7%) than from Martinique (15.6%) (p < 0.001). The overall seroprevalence rate
      was similar to the rate observed in young recruits from mainland France in 1990.
      These findings indicate that hepatitis A has decreased in the French West Indies
      in agreement with improvements with sanitary and housing conditions. This study
      also supports vaccination of recruits from DOM-TOM against hepatitis A after
      control of their immune status.

PMID- 9026593
TI  - [AIDS and health personnel in Ivory Coast].
AB  - During the second half of 1993, a survey to assess awareness, attitudes, habits,
      and behavior with regard to HIV and AIDS was performed among health care workers
      in the Cote d'Ivoire. A total of 90 health care workers, 42 in Abidjan and 48 in
      Daloa, were surveyed. The majority (87%) were women. Understanding of the terms
      "AIDS" and "seropositivity" was good as was knowledge of AIDS-related symptoms.
      Awareness was better among newly recruited workers and nurses than among
      orderlies. Appreciation of risk was strongly linked with the notion of high-risk
      population. The occupational nature of the risk was clearly understood and
      anxiety in this regard was increased by uncertainty as to modes of secondary
      transmission and lack of preventive measures. On the individual and personal
      level protection consisted mainly in reducing the number of partners and outside
      activities. There was a great demand for training and information. As a result of
      the uncertainties revealed in this survey there appears to be a reluctance or
      refusal to perform certain procedures or treat certain patients and even a
      tendency to abandon the health care profession.

PMID- 9026594
TI  - [Diabetes in Cameroon. Classification difficulties in Africa].
AB  - Diabetes is a major health problem in Africa where management is complicated by
      poor socioeconomic conditions. Atypical presentations of diabetes appear to be
      common in tropical countries although there is still little accurate data in this
      regard. We describe 550 diabetic patients treated in Cameroon between December
      1990 and July 1994. According to WHO criteria 136 of these patients (24.7%) were
      classified as insulin-dependent (IDDM), 405 (73.5%) as non-insulin-dependent
      (NIDDM), and 9 as secondary diabetes (1.6%) related to other diseases. There were
      no cases of malnutrition-related diabetes but 18 patients (3%) met the criteria
      for "African diabetes" defined by Cuisinier-Raynal. Study of this cohort revealed
      several differences with diabetic populations in industrialized countries.
      Insulin-dependent diabetes was observed in all age groups with a mean age of
      onset 40.0 +/- 14.8 years which is close to the mean age of onset of non-insulin
      dependent diabetes (49 +/- 10.9 years). The overall M/F sex ratio was 1.63
      demonstrating a clear-cut male predominance. There was a high incidence of non
      insulin-dependent diabetes in young, non-obese subjects. In many cases
      classification was difficult because insulin requirements fluctuated greatly. The
      incidence of obesity in non-insulin-dependent diabetic patients was lower than in
      industrialized countries. These findings suggest the existence of a tropical
      diabetes syndrome unrelated to malnutrition. Thus African diabetes appears to be
      another aspect of the disease which has a variety of heterogeneous etiologic
      features that cannot be classified on the basis of available data. The current
      WHO system does not take atypical African diabetes into account.

PMID- 9026596
TI  - [HIV infection manifesting as a pneumococcal spondylodiscitis].
AB  - In this report the authors describe a patient in whom pneumococcal spondylitis
      was the presenting manifestation of HIV infection and discuss bone and joint
      infections during HIV infection. The case report involves a 43-year-old man from
      Mali who was admitted for fever and back pain that occurred during upper airway
      infection. Pneumococcal spondylitis was diagnosed based on MRI images showing an
      epidural effusion and on positive hemocultures for Streptococcus pneumoniae.
      Initial standard x-ray findings were normal but repeat imaging revealed the disco
      vertebral lesions. HIV serology was positive but there was no evidence of
      immunodepression or decreased CD4 lymphocyte levels. Since the introduction of
      antibiotics bone and joint involvement in pneumococcal disease has become
      uncommon in developed countries. In patients with HIV infection pyogenic
      arthritis is rare but the risk of pneumococcal disease is greatly enhanced and
      arthritic lesions can occur. Only eleven cases of pneumococcal arthritis
      associated with HIV infection have been reported in the literature. However the
      incidence of these infections seems higher in Black Africa where they account for
      50% of pyogenic arthritis. The authors emphasize the lack of correlation between
      the stage of HIV infection and the onset of pneumococcal osteoarthritic
      infections which could account for occurrence of the latter as presenting
      manifestations of retroviral seropositivity.

PMID- 9026595
TI  - [Value of hepatosplenic ultrasonography in the surveillance of Schistosoma
      mansoni endemics (a study conducted in the Richard Toll region of Senegal)].
AB  - Abdominal ultrasound is a reliable and reproducible technique for monitoring the
      progression of hepatosplenic schistomiasis. It was used in the framework of the
      @Hope" program against endemic Schistosoma mansoni in the Senegal River region. A
      total of 166 patients presenting Schistosoma mansoni eggs in stools were divided
      into age groups with a sex ratio of 1. All patients underwent the same ultrasound
      examination including measurement of the liver and assessment of the branches of
      the portal vein system. Our findings indicated that highly sensitive hypertrophy
      of the left lobe of the liver occurs early since this feature was observed in all
      patients over the age of 15 years. Alterations of the portal system were observed
      in 73% of patients but were moderate, stage 1, in the zone where incidence of
      positive stools is over 90%. Grade III lesions were only found in patients over
      23 years of age. Although these lesions accounted for 4% of the cases, this
      finding underscores the need for surveillance in a region where infestation
      became endemic less then ten years ago raising fears that severe schistosomal
      portal hypertension would become widespread. A mobile ultrasonographic
      surveillance unit would be useful in the region.

PMID- 9026597
TI  - [Primary pneumococcal peritonitis in children].
AB  - Since the advent of antibiotics primary pneumococcal peritonitis rarely occurs
      except in association with immunodepression and a detectable port of entry
      involving the lung, upper airways, or female genital tract. This clinical picture
      was observed in an 8-year-old girl who underwent surgery after an initial
      diagnosis of appendicitis-related peritonitis. Surgical exploration revealed a
      macroscopically and microscopically normal appendix and purulent peritoneal
      effusion. Culture of a peritoneal fluid specimen identified a pneumococcus
      sensitive to beta-lactam agents. Samples from the throat, urine, and vulva as
      well as blood cultures were negative. The patient responded favorably to
      ampicillin and gentamicine. The authors review the features of pneumococcal
      peritonitis and emphasize the high incidence of concomitant genital tract
      infection.

PMID- 9026598
TI  - [Pygomelus. An African surgical case report].
AB  - Pygomelus is a malformation characterized by the presence of one or more extra
      extremities in the pelvic region. This article describes a case of pygomelus
      involving a child in Cote d'Ivoire. It is the tenth operated case to be reported
      in the literature. The malformation consisted of a well developed third lower
      extremity attached to the right iliac crest, without a rudimentary pelvis, and of
      a poorly developed upper extremity attached to the subpubic region. The two extra
      extremities were removed surgically without complications. Pygomelus is an
      uncommon malformation whose nosologic limits are unclear since it is comparable
      to lower extremity duplication and dipygus. According to the authors pygomelus is
      a more appropriate term than caudal duplication which is widely used in English
      speaking physicians.

PMID- 9026599
TI  - [Viral hepatitis E].
AB  - Thanks to progress in serologic techniques evidence was obtained in 1980 showing
      that acute hepatitis epidemics observed in India were due to neither virus A nor
      virus B. The presence of another virus was confirmed and its genome was cloned
      and sequenced in 1991. Hepatitis virus E is a small RNA virus that differs from
      other known human viruses. Man and probably a few animal species maintain
      dissemination by the fecal route. Subjects not previously contaminated are
      susceptible and produce protective antibodies. Contamination occurs by the fecal
      oral route general from water or tainted food. Direct contamination is rare.
      Vertical transmission from mother to fetus can also be observed. Outbreaks of the
      disease are characterized by epidemic proportions, preferential involvement of
      adolescent and young adults, and high incidence of fulminant cases especially in
      pregnant women. Outbreaks have been observed in endemic settings in southern
      Asia, Africa, and Mexico where sporadic cases are observed. Endemic areas are
      found in all developing countries. Hepatitis E is not clinically different from
      other acute viral hepatitis. Asymptomatic forms are common especially in
      children. The course of the disease is usually benign with little risk of
      development of chronic symptoms and cirrhosis. However hepatitis E is associated
      with a high incidence of severe cases with a mortality of 1 to 2% from icteric
      forms which occur in 15 to 20% of cases involving women contaminated during the
      last three months of pregnancy. Diagnosis can be made using either synthetic
      proteins or recombinant peptides. for the epitopes of the virus. Prevention
      depends on protection of the water supply and proper sewage disposal. Successful
      active immunization of monkeys holds promise for development of a vaccine. Due to
      its magnitude and high mortality rate hepatitis E is a major health problem for
      numerous regions around the world including Southeast Asia.

PMID- 9026600
TI  - [Update on the dracunculosis eradication program].
AB  - Dracunculiasis has been described since antiquity and will be forever associated
      with the image of the method of extraction consisting of winding a few
      centimeters of the worm around a stick every day. For nearly ten years a
      worldwide effort to eradicate this infection has been under way. Achieving this
      apparently simple goal is hindered by the difficulties in accessing infected
      areas and by the dire poverty in the regions involved which include the "poorest
      of the poor". Spectacular results have been accomplished in Pakistan thanks to
      the concerted efforts of political, financial, and technical officials from a
      number of national and international organization. While the rate of infestation
      has decreased by 90% worldwide, the final push to complete eradication is the
      most difficult and, as in India and Mali, is being oriented towards a strategy
      involving an integrated approach. Results are slow and gradual but notable and
      durable progress has been made in terms of village water supply. It is necessary
      that intervention in these areas be associated with other poverty-fighting
      programs. Successful eradication without accompanying improvements would be a
      technical victory but in terms of public health and welfare such a victory would
      correspond to an unjustifiably missed opportunity.

PMID- 9026601
TI  - [Medical management of exchange students traveling to an isolated tropical
      milieu: an experience in western Ivory Coast].
AB  - Thirty-one students from a French rural engineering school spent a six-week
      training period in an isolated tropical forest environment in western Cote
      d'Ivoire. They received preventive medical treatment before departure and were
      kept under constant surveillance. Because the group was multiethnic and divided
      into four separate work teams, communication was a major problem. Regular
      prevention and continuous care allowed control of the fever episodes which
      occurred in one half of the group presumably from malaria. Since laboratory tests
      could not be performed, diagnosis and treatment were undertaken presumptively. In
      this regard the ParaSight-F test would have been highly useful. The second most
      common manifestations in this susceptible population in an unfamiliar and hostile
      environment were psychiatric in nature. This finding underscores the need for
      better screening before departure. The multipurpose first aid kit was adequate.
      This experience could be helpful to physicians responsible for managing groups
      traveling in areas where sanitary conditions are poor.

PMID- 9026602
TI  - [Tuberculosis in the Federal Islamic Republic of Comores in 1995].
AB  - Tuberculosis is still a major health concern in the Federal Islamic Republic of
      the Comoros. An effective nationally organized program has been set up to fight
      against the disease. It is based on bacteriologic screening (105 new cases of BK+
      disease since 1995) and quadruple chemotherapy in patients identified (2RZHE 4RH)
      with in-hospital starter treatment for 2 months and supervised outpatient
      treatment for 4 months. Patients are followed up monthly. Because of these
      measures and given the fact that access to health care is excellent (small island
      nation), compliance has been over 90% for several years and the overall rate of
      cure was around 92% in 1995. From an epidemiologic standpoint the endemic status
      of tuberculosis in the Comoros has been stable with an overall incidence of about
      25 cases per 100,000 inhabitants in the last 5 years. Extrapulmonary forms and
      relapses are uncommon (5.4% and 6.2% respectively in 1995). The incidence of
      positive HIV1 serology in the general population of the Comoros is low and has
      not been a complicating factor since no seropositive BK+ patient has been
      identified since the beginning of systematic surveillance in 1988.

PMID- 9026603
TI  - [Results of sequential prolonged courses of albendazole and praziquantel in
      recurrent neurocysticercosis].

PMID- 9026604
TI  - [Identification of Leishmania (V) guyanensis during recurrences of cutaneous
      leishmaniasis contracted in French Guyana].

PMID- 9026605
TI  - [Hepatitis C seropositivity after multiple transfusions in sickle cell anemia
      patients in Yaounde, Cameroon].

PMID- 9026606
TI  - [Perioperative complications of thyroid surgery in the University Medical Center
      of Lome, Togo].

PMID- 9026608
TI  - [Tropical cardiovascular diseases. Proceedings of the 3rd Pharo and Laveran
      Hospital meeting. 6-7 September 1996].

PMID- 9026607
TI  - [Severe secondary reactions related to ivermectin treatment in patients with
      loiasis].

PMID- 9026609
TI  - [Biological and therapeutic particularities of non-complicated hypertension in
      sub-Saharan Africa].

PMID- 9026610
TI  - [Therapeutic approach in malignant hypertension in developing countries].

PMID- 9026611
TI  - [Epidemiology and pathogenesis of acute rheumatoid arthritis].

PMID- 9026612
TI  - [Epidemiological aspects of acute rheumatoid arthritis in the Maghreb countries].

PMID- 9026613
TI  - [Epidemiological aspects of acute rheumatoid arthritis in the South Pacific].

PMID- 9026614
TI  - [Management of acute rheumatoid arthritis in French Polynesia].

PMID- 9026615
TI  - [Cardiomyopathies. Definition and classification].

PMID- 9026616
TI  - [The heart and AIDS].

PMID- 9026617
TI  - [The heart and parasitic diseases].

PMID- 9026618
TI  - [Postpartum cardiomyopathy].

PMID- 9026619
TI  - [The heart and travel].

PMID- 9026620
TI  - [Cardiovascular diseases and their evolution in developing countries].

PMID- 9026622
TI  - [Health promotion at the workplace--selected questions on implementation].
AB  - Health promotion viewed as health enhancement achieved mainly through stimulating
      and instilling health conducive behaviours (life styles) is now generally
      acknowledged, both in the theory and in the practice of health care as a
      principal means for preserving and increasing health potential of an individual
      and community.

PMID- 9026621
TI  - [Epidemiological aspects of hypertension in the black patient].

PMID- 9026623
TI  - [Mortality from malignant neoplasms in men occupationally exposed to asbestos
      dust].
AB  - The authors present the results of cancer risk evaluation in the cohort of men
      occupationally exposed to chrysotile asbestos dust in the plant involved in the
      production of asbestos packings, uneven fabric, yarn, cords, asbestos and rubber
      cardboards and friction materials. A retrospective observation, carried out till
      31 December 1990, covered 2,403 men employed during the years 1945-73. The cohort
      accessibility accounted for 90.5%. Cancer risk was evaluated on the basis of
      standardized mortality ratio (SMR) calculated according to the person-years
      method. A slightly higher mortality from malignant neoplasms was found in the
      cohort than in the general population (160 deaths; SMR = 108). A significant
      excess mortality applied only to one site, namely large intestine (9 deaths; SMR
      = 232). In the subcohort of workers exposed to a high dose of asbestos dust, a
      significant increase in total cancer risk was revealed (30 deaths; SMR = 150),
      including neoplasm of stomach (8 deaths; SMR = 223), large intestine (3 deaths,
      SMR = 582) and liver (3 deaths, SMR = 373). No significant increase in mortality
      from lung cancer was observed.

PMID- 9026624
TI  - [Influence of vapours of paint and toxic dusts on mucous membranes of the upper
      airways in paint and varnish factory workers].
AB  - Macroscopic, cytologic and bacteriologic conditions of mucous membranes of the
      upper airways in workers (n = 146) of the Polifarb Factory, Wroclaw, exposed to
      dusts and solvent vapours used in the paint and varnish production was estimated.
      In 89% of the workers, pathologic changes in throat mucous membranes were
      observed. Three types of macroscopic changes were distinguished. In workers with
      the shortest period of employment, laryngeal oedema congestion alteration was
      diagnosed, and atrophic changes with medium intensity were observed in workers
      employed for a long period. It was found that cytologic changes in the nose
      mucous membrane depended on the duration of exposure. Inflammation cytograms
      appeared during the first period of exposure to the substances discussed. The
      longer period of exposure, the more clear features of metaplasia squamous
      epithelium. The composition of the nose and throat bacterial flora changed
      according to the length of employment. An increased growth of G(-) genera
      Enterobacter, Klebsiella, Proteus, Escherichia and Candida fungi was found in
      workers with long period of employment.

PMID- 9026625
TI  - [Occupational exposure to organic solvent vapors among workers in industrial
      enterprises of Estonia].
AB  - To ascertain the overall picture of occupational exposure to benzene, styrene,
      acetone and ethanol in workers employed in the industrial enterprises of Estonia,
      the concentration of solvent vapours in the workers' breathing zone was
      determined, applying passive monitors. The correlation between urine mandelic
      acid concentration and that of styrene in the workers' breathing zone was
      estimated: r = 0.7055; p = 0.02. The results obtained showed that the
      concentration of benzene, styrene, acetone and ethanol vapours in the workers'
      breathing zone exceeded in many cases maximum permissible levels (5 mg/m3, 10
      mg/m3, 200 mg/m3, 1000 mg/m3).

PMID- 9026626
TI  - [Occupational-social influence in the course of cholelithiasis].
AB  - The aim of the study was to examine the relationship between the work load,
      evaluated by the occupational activity, and the incidence of cholelithiasis. In
      total 372 subjects (169 cholelithiasis patients examined using USG, and 203
      controls), hospitalised in 1993 in the Department of Gastroenterology, Regional
      Hospital, Bialystok, completed the questionnaire. Attention was also given to
      age, sex, permanent residence, education and physical activities after work. A
      moderate physical effort, both occupational and non-occupational, seemed to
      reduce the risk of cholelithasis.

PMID- 9026627
TI  - [Reliability of routine measurements of atmospheric air pollution using sulfur
      dioxide as an example].
AB  - On the basis of an external quality control of sulfur dioxide measurements in the
      atmospheric air (emission), the preparation of control material, its evaluation
      and a two-week durability of the material are presented. The results of the
      control test carried out in autumn 1994 is also discussed.

PMID- 9026628
TI  - [Genetic examinations in health care].
AB  - Genes are one of the most important indicators of disease incidence. Almost each
      diseases results from incorrect function of one or more genes. The disclosure of
      disease genetically conditioned depends, in many cases, on the effect of a broad
      spectrum of different environmental factors. Screening tests for carries of
      defective genes play a key role in the detection of risk for genetically
      conditioned diseases. Screening tests carried out for many years yielded a very
      diversified results. Some of them, for example, the screening test for the gene
      responsible for Tay-Sachs disease, produced good results, whereas results of
      other tests, like the test for the gene responsible for crescent anaemia, proved
      to be unsatisfactory. Among genetically conditioned diseases, neoplastic diseases
      are the subject of particular interest. It is already known that these diseases
      may be attributed to the accumulation of genetic errors in a normal cell, and
      that this phenomena applies to certain categories of genes. An analysis of
      genetic material of persons from the families with higher cancer incidence
      revealed the relationship between cancer and inheritance of some defective genes.
      Nevertheless, it should be stressed that the development of cancer is not
      definitely foregone even if genetic features of cancer disease are detected in a
      given person. The presence of such features only indicates an inborn or acquired
      defect (as a result of mutation) that predisposes him/her to illness. A great
      progress in molecular oncology made during the last years and the development of
      genetic maps relevant to neoplastic diseases should contribute to the detection
      of such genetic markers which could facilitate the identification of persons with
      a higher risk for neoplastic diseases and allow to take relevant preventive
      measures in due time.

PMID- 9026629
TI  - [Professional work of woman as a risk factor for circulation disorders].
AB  - The author presents an up-dated review of the literature on the effects of
      professional work on the incidence of diseases of the circulatory system in
      women, and the incidence of ischaemic heart disease and arterial hypertension in
      particular. An analysis of health effects of professional work revealed that a
      limited influence on the final effect of own work (a limited control of own
      situation at work) and subordination to superiors, belong to these factors which
      exert the most detrimental effect on the circulatory system. A negative effect
      frequently manifested by the level of blood pressure is also related with heavy
      physical burden. The literature data also reveal that the professional work,
      itself, does not contribute to an increased incidence of diseases of the
      circulatory system or to the profile of risk factors. A possible reason for this
      observation lies in similar responsibilities faced by women acting only as
      housewives and those faced in occupational work. The review presented also
      stresses the role of endogenic risk factors in women related with the number of
      pregnancies/deliveries as well as with menopause.

PMID- 9026631
TI  - [Oncoproteins and anti-oncoproteins in blood serum as biomarkers of early health
      effects induced by occupational and environmental carcinogens].
AB  - Over a whole life-span a genetic machinery of human cells is exposed to
      carcinogenic effect of various chemical, physical and biological factors leading
      to cellular changes in the genome like point mutation and translocation or
      amplification of genes. Together with growing an ageing of the human organism,
      the number and heterogeneity of mutated cells increase. Thus, the presence or
      absence of the neoplastic process may depend on the length of life, efficiency of
      the immunological system, cumulation of adverse affects of environmental factors
      or inherited susceptibility to a disease. There is no doubt that neoplasms which
      develop due to inheritance of different genetic defects or due to direct
      environmental effect progress in line with similar mutations, resulting finally
      in the genome destabilisation and disturbances in the balance between
      proliferation and differentiation processes. The knowledge as to how far
      environmental carcinogens affect cellular genome is still limited. Nevertheless,
      data collected to date help to understand the mechanisms by which environmental
      carcinogens may initiate the process of transforming normal cells into neoplastic
      ones. It is most likely that activation of some oncoproteins and deactivation of
      some suppressive genes and related qualitative and quantitative changes in
      oncoproteins and anti-oncoproteins participating in the growth control and
      cellular division, are the essential mechanisms which are involved in this
      process. The discovery that activation of oncoproteins and related emergence of
      oncoprotein in cells, increased in the number of changed, can be monitored in
      easily available biological fluids, such as blood or urine, has become of great
      importance for occupational medicine and environmental health. That has provided
      new diagnostic measures for evaluating carcinogenic effects of the working and
      living environments. The fact, that the emergence of oncoproteins in biological
      fluids may precede by many months or even years clinical manifestations of
      neoplastic disease should greatly contribute to undertaking more effective
      preventive measures.

PMID- 9026630
TI  - [Methods of extrapolating risk from from high to low doses and their effect on
      determining MAC values].
AB  - The author discussed problems arising from the use of different mathematical dose
      response models for extrapolation of cancer risk from high to low doses. On the
      one hand, a linearized, multistage model, commonly used for evaluating cancer
      risk resulting from exposure to chemical carcinogens in the communal environment,
      frequently underestimates a real risk. On the other hand, the application of
      nonlinear models for describing the relationship between exposure and response
      sizes in occupational exposures, and linearized ones in communal exposures leads
      to ridiculous assessments, namely it sometimes appears that an inhabitant of Lodz
      is at the same cancer risk caused by inhalation exposure to benzo(a)pyrene like a
      worker employed in the coke-chemical industry and exposed to doses a dozen times
      higher than MAC values. A considerable overestimation of risk will also yield
      additional problems related with the acceptance of these values. Therefore, the
      author proposed to use, whenever possible, nonlinear models for establishing dose
      response relationships both in communal and occupational exposures, and maximum
      likelihood method for estimating model parameters.

PMID- 9026632
TI  - [An attempt to identify an increased incidence of occupational laryngeal diseases
      in teachers].
AB  - The author postulates the causes of an increased incidence of occupational
      diseases of the voice organ in teachers. The most frequent causes are: improperly
      performed prophylactic examinations, inadequate supervision over the teachers'
      work environment and lack of knowledge of physiology of the voice organ and
      techniques of its use from the teachers' perspective. The author also stresses
      the economic aspects involved in the diagnosis of an occupational disease, and
      she recommends to develop and implement preventive programmes.

PMID- 9026633
TI  - [Laboratory animals as a cause of occupational allergy].
AB  - Animal allergens are the strongest occupational allergens which sensitize the
      respiratory tract. Allergy to the animal is the most important occupational
      health hazard among people working with experimental animals in university and
      other research laboratories. The most common manifestations of allergy to
      laboratory animals are: bronchial asthma, rhinitis, contact urticaria, angioedema
      and contact dermatitis. The major source of allergen is the excreta and secreta
      of such animals as: rat, mouse, guinea pig, rabbit, dog, cow and horse. Among
      risk factors responsible for the development of animal allergy are: atopy,
      tobacco smoking and allergy to domestic pets. The diagnosis of laboratory animal
      allergy is usually based on a medical history. The objective evidence to support
      the diagnosis can be obtained from skin testing, a specific immunologic response
      and work related changes in peak flow rate. Reduction in the airborne levels of
      animal allergens not only at home, but also at work (proper ventilation, filter
      masks, elimination of domestic animals) and reduction of factors responsible for
      the development of bronchial hyperreactivity (avoidance of smoking), can
      contribute to decreasing the incidence of diseases.

PMID- 9026634
TI  - The hmu locus of Yersinia pestis is essential for utilization of free haemin and
      haem--protein complexes as iron sources.
AB  - Yersinia pestis strains utilize haem and several haem-protein complexes as sole
      sources of iron. In this study, the haemin uptake locus (hmu) of Y. pestis KIM6+
      was selected from a genomic library by transduction into an Escherichia coli
      siderophore synthesis (entC) mutant. Recombinant plasmids containing a common 16
      kb BamHI insert were isolated that allowed E. coli entC to use haemin as an iron
      source. An 8.6 kb region of this insert was found to be essential for haemin
      utilization and encoded at least five proteins with molecular masses of 79/77,
      44, 37, 35, and 30/27.5 kDa. A 10.9 kb Clal fragment containing the hmu locus
      showed varying degrees of homology to genomic DNA from Yersinia
      pseudotuberculosis, Yersinia enterocolitica, and other genera of
      Enterobacteriaceae. An E. coli hemA aroB strain harbouring cloned hmu genes used
      haemin as both an iron and porphyrin source but only on iron-poor medium,
      suggesting that haemin uptake is tightly iron regulated. Additionally,
      haemoglobin and myoglobin were used as iron sources by an E. coli entC (pHMU2.2)
      strain. Deletion of the hmu locus from Y. pestis KIM6+ chromosome generated a
      mutant that grew poorly on iron-depleted medium containing free haemin as well as
      mammalian haem-protein complexes including haemoglobin, haemoglobin-haptoglobin,
      myoglobin, haem-haemopexin, and haem-albumin unless it was complemented with
      cloned hmu genes.

PMID- 9026635
TI  - Expression and purification of retroviral HIV-1 reverse transcriptase.
AB  - Modern molecular biology techniques have provided valuable tools which allow for
      the expression of large amounts of enzyme in E. coli. For potential therapeutic
      targets such as HIV-1 reverse transcriptase, it is desirable that the enzyme
      studied is pure and correlates to the active form of the enzyme found in vivo.
      This poses a particular challenge for those researchers studying HIV-RT since a
      significant degree of heterogeneity is introduced by nonspecific proteolytic
      cleavage of the p66 subunit by E. coli proteases. The advantage of the
      purification protocol presented here is that the association of monomers is
      facilitated by mixing an excess of p51 subunit, which is truncated at a site that
      is N-terminal to known bacterial cleavage sites, with p66 protein. This avoids
      enzymatic processing of the larger subunit since the formation of heterodimeric
      RT is rapid and the dimer is stable against proteolytic cleavage. Therefore, it
      is possible to isolate a pure homogeneous p66/p51 heterodimer. An enzyme prepared
      in this manner yields crystals that defract to a 3.2-A resolution. It has also
      been used to study both sensitivity of HIV-1 RT mutants to azidothymidine
      triphosphate and the kinetics of a potent nonnucleoside RT inhibitor (L-743,726).
      Finally, it is interesting to note the similarity of HIV-1 RT with reverse
      transcriptases from other lentiviruses (FIV and EIAV RT). Both of these enzymes
      consist of heterodimers of p66 and p51 subunits and share other biophysical
      characteristics. Purification of these reverse transcriptases can, in all
      likelihood, be optimized by using methods similar to those described in this
      chapter.

PMID- 9026636
TI  - Expression, purification, and characterization of DNA polymerases involved in
      papovavirus replication.
AB  - In recent years, work from a large number of laboratories has greatly expanded
      our knowledge of the biochemical characteristics and the genetic structure of the
      DNA polymerases used during papovavirus DNA replication. The development of in
      vitro DNA replication systems for both SV40 and polyoma virus has been paramount
      in facilitating the development of the current models describing how DNA
      polymerase alpha and delta function to replicate the genomes of these two
      viruses. Our studies have demonstrated that the proteins recognized to be
      essential for both in vitro SV40 and polyoma viral origin-dependent DNA synthesis
      can be isolated from cells as an intact complex. We have shown that the human
      cell MRC closely resembles the murine cell MRC, in both its protein composition
      and its fractionation and chromatographic profile. In addition, our data
      regarding both the human and the murine MRC support the dipolymerase model
      proposed from in vitro DNA replication studies using reconstituted assay systems.
      In addition, analysis of the nucleotide sequence of the genes encoding DNA
      polymerase alpha and delta has revealed that the amino acids encoded by several
      regions of these two genes have been rigorously maintained across evolutionary
      lines. This information has permitted the identification of protein domains which
      mediate the complex series of protein-protein interactions that direct the DNA
      polymerases to the cell nucleus, specify complete or partial exonuclease active
      sites, and participate in the interaction of each DNA polymerase with the DNA
      template. Expression studies examining each of the genes encoding DNA polymerase
      alpha and delta clearly indicate that both DNA polymerases are cell cycle
      regulated and undergo a dramatic induction in their expression when quiescent
      cells are stimulated to enter the cell cycle. This is in contrast to the two- to
      three-fold upregulation in the level of expression of these two genes when
      cycling cells cross the G1/S boundary. In addition, both proteins are
      phosphorylated in a cell cycle-dependent manner, and phosphorylation appears to
      be mediated through the action of a cdc2-dependent protein kinase. Despite all of
      this new information, much remains to be learned about how papovavirus DNA
      replication is regulated and how these two DNA polymerases act in vivo to
      faithfully copy the viral genomes. Studies have yet to be performed which
      identify all of the cellular factors which potentially mediate papovavirus DNA
      replication. The reconstituted replication systems have yielded a minimum number
      of proteins which are required to replicate SV40 and polyoma viral genomes in
      vitro. However, further studies are needed to identify additional factors which
      may participate in each step of the initiation, elongation, and termination
      phases of viral genome replication. As an example, models describing the
      potential role of cellular helicases, which are components of the MRC isolated
      from murine and human cells, have yet to be described. It is also conceivable
      that there are a number of other proteins which serve to attach the MRC to the
      nuclear matrix, stimulate viral DNA replication, and potentially regulate various
      aspects of the activity of the MRC throughout viral DNA replication. We are
      currently working toward characterizing the biochemical composition of the MRC
      from both murine and human cells. Our goals are to identify all of the structural
      components of the MRC and to define the role of these components in regulating
      papovavirus and cellular DNA replication. We have also begun studies to visualize
      the spatial organization of these protein components within the MRC, examine the
      regulatory processes controlling the activity of the various components of the
      MRC, and then develop this information into a coherent picture of the higher
      order structure of the MRC within the cell nucleus. We believe that this
      information will enable us to develop an accurate view of the detailed processes
      mediating both pa

PMID- 9026637
TI  - Expression, purification, and characterization of the herpes simplex virus type-1
      DNA polymerase.

PMID- 9026639
TI  - Expression and characterization of hepadnavirus reverse transcriptases.

PMID- 9026638
TI  - Heterologous expression, purification, and characterization of adenovirus DNA
      polymerase and preterminal protein.

PMID- 9026640
TI  - Expression, purification, and characterization of vaccinia virus-encoded RNA and
      poly(A) polymerases.

PMID- 9026642
TI  - Isotopic assays of viral polymerases and related proteins.

PMID- 9026641
TI  - Viral polymerase-associated 5'-->3'-exonucleases: expression, purification, and
      uses.

PMID- 9026643
TI  - Nonisotopic assays of viral polymerases and related proteins.

PMID- 9026644
TI  - Catalytic activities associated with retroviral and viral polymerases.

PMID- 9026645
TI  - Purification of viral polymerases: general considerations.

PMID- 9026646
TI  - Approaches to high-volume screening assays of viral polymerases and related
      proteins.

PMID- 9026647
TI  - In situ DNA polymerase and RNase H activity gel assays as applied to hepadnavirus
      particles.

PMID- 9026648
TI  - A system to analyze and identify inhibitors of HIV-1 gene regulation using a
      defective integrated provirus.

PMID- 9026649
TI  - Assays for poliovirus polymerase, 3D(Pol), and authentic RNA replication in HeLa
      S10 extracts.

PMID- 9026650
TI  - Preparation and use of synthetic oligoribonucleotides as tools for study of viral
      polymerases.

PMID- 9026651
TI  - Use of bacteriophage RNA polymerase in RNA synthesis.

PMID- 9026652
TI  - Inhibition of viral polymerases by chain-terminating substrates: a kinetic
      analysis.

PMID- 9026653
TI  - Design of nucleoside analog inhibitors of herpesvirus polymerases.

PMID- 9026654
TI  - Development of nonnucleoside HIV reverse transcriptase inhibitors.

PMID- 9026655
TI  - Analysis of inhibition of retroviral reverse transcriptase.

PMID- 9026656
TI  - Novel methods of generating specific oligonucleotide inhibitors of viral
      polymerases.

PMID- 9026657
TI  - Analyzing the fidelity of reverse transcription and transcription.

PMID- 9026658
TI  - Site-directed mutagenic analysis of viral polymerases and related proteins.

PMID- 9026659
TI  - Analysis of resistance mutants of viral polymerases.

PMID- 9026660
TI  - RNA-dependent RNA polymerase of hepatitis C virus.

PMID- 9026662
TI  - Expression, purification, and characterization of orthomyxovirus: influenza
      transcriptase.

PMID- 9026661
TI  - Characterization of coronavirus RNA polymerase gene products.

PMID- 9026663
TI  - Expression, purification, and characterization of rhabdovirus polymerase.

PMID- 9026664
TI  - [Dermatophagoides pteronyssinus mites in the Republic of Tajikistan].
AB  - Studies were first carried out in the Republic of Tadjikistan to identify
      Dermatophagoides mites [correction of ticks]. They showed that they were present
      in the domestic dust from the bedding of patients with bronchial asthma. Their
      sensitivity to the allergen of domestic dust was determined.

PMID- 9026665
TI  - [Standards for reviewing preparations in the study of ixodid tick nymphs by dark
      field microscopy in borreliosis foci].
AB  - The results of dark-field microscopy of 73 positive preparations from the unfed
      Ixodes persulcatus Sch. nymphs collected in the Perm Region of Russia have been
      analysed. The preparations were prepared by cutting the ticks placed into a
      physiological saline drop with needles. The numbers of Borrelia in the
      preparations varied from 0.4 to 173.6 per 100 microscopic fields (mean 22.9). It
      has been demonstrated that if all the standard conditions are fulfilled
      (magnification 600), drop volume 0.005 mil covering 18 x 18 mm glasses), it is
      practically impossible to overlook an infected nymph while examining 250
      microscopic fields in such a preparation. The above-described conditions ensure
      valid reliable results of Borrelia calculation and their concentration
      measurements. The differences in the individual Borrelia infection rates in
      nymphs may be expressed by using the scale: low (up to 10), moderate (10.1-50),
      and high (above 50 Borrelia per 100 microscopic fields).

PMID- 9026666
TI  - [Experience in using traps for collecting the eggs deposited by the urban
      mosquito (Culex pipiens)].
AB  - Egg-traps detect Culex pipiens when other methods (mosquito recording in the
      premises, registration of its attacks and, interview with people) yield negative
      results. This allows one to assess the rates of its water reservoir occupation
      and breeding with regard to less time spent and greater hygienic efforts. In the
      place under study, C.pipiens females make their first cycle autogenously in the
      immediate vicinity of a breeding place and fly away only after termination of the
      first egg-laying.

PMID- 9026667
TI  - [The insecticidal capacity and level of the toxicity of the new insecticidal
      preparation of the pyrethroid series--Bistar].

PMID- 9026668
TI  - [The reaction of the tick Hyalomma asiaticum (Acarina, Ixodidae) to 1- to 4-GHz
      microwaves].
AB  - Low-energy microwave radiation in the frequency range in question was found to
      exert a noticeable biological action on H. asiaticum. Radiation delayed larval
      hatch by 3-20 days, increased the activity duration of newly moulted larvae by 17
      24 days, reduces the survival of hungry larvae and nymphs by 4-10 days. The
      efficiency of the biological action of microwaves is enhanced by impairments in
      the natural developmental rhythm of the tick.

PMID- 9026669
TI  - [The interrelations of mucosal epithelial cells with microbes--intracellular
      parasites].
AB  - On the basis of information at hand, it can be concluded that there are principal
      limits on the capture of bacteria by epithelial cells in the gastrointestinal
      tract and other cavities. Although entry is, however, a result both of bacteria
      and epithelial cells, it is frequently induced by parasite-directed endocytosis
      and may also accompanied by passive entry of nonpathogenic bacteria. The
      induction of parasite-induced endocytosis should be regarded as a consequence of
      a fundamental concept in biology, namely: molecular and cellular recognition
      wherein bacterial adhesion to the host's cell receptors is of great importance.
      In this connection, discussion covers the origin of corresponding receptors. The
      authors share the opinion in that epithelial cells, those of the gastrointestinal
      tract in particular, are part of the human common mucosal immune system.

PMID- 9026670
TI  - [Helminthiasis morbidity in an organized pediatric population in one of the
      regions of the Far North].
AB  - In 1991-1992, higher affection rates of diphyllobothriasis and enterobiasis were
      notified in some groups of the organized children living on the Pur River (the
      Yamalo-Nenets Autonomous Okrug). The children are infected by Diphyllobothrium in
      infancy, the risk of infection is rather high, reinfections are observed. Among
      other things, this makes it necessary to perform systematic educational studies
      among the population in their different forms.

PMID- 9026671
TI  - [Changes in the activity of gamma-glutamyltransferase and cholinesterase in the
      blood of patients with opisthorchiasis at different phases of the disease].
AB  - The plasma activity of gamma-glutamyl transferase (GGT) and cholinesterase (CE)
      was assayed in 79 patients with opisthorchiasis in its active and chronic
      periods, as well in different periods after anthelminthic therapy with biltricide
      and azinox. The mean values of CE activity did not significantly differ between
      the groups of the examinees. The probability of decreased CE synthesis in the
      residual period was significantly greater in the treatment of chronic than acute
      opisthorchiasis. The maximum activity of GGT was found in acute opisthorchiasis,
      its values were also significantly higher than the control ones and remained
      unchanged within a year after anthelminthic therapy. Possible causes of delayed
      normalization of enzymatic activity following the treatment of chronic versus
      acute opisthorchiasis are discussed in the paper.

PMID- 9026673
TI  - [The technology for manufacturing antiparasitic preparations. 7. Preparation G
      1460 and its use for the treatment of monieziasis and intestinal nematodiases].
AB  - A procedure was developed for the synthesis of the anthelminthic G-1460. The
      therapeutical doses (20 and 25 mg/kg) of the agent were defined for the treatment
      of monieziasis and gastrointestinal nematodes on an individual basis.

PMID- 9026672
TI  - [The technology for manufacturing antiparasitic preparations. 6. The development
      of a technology for producing the anthelmintic Azinox (praziquantel) and the
      evaluation of its toxic and anthelmintic properties].
AB  - The paper outlines a procedure for manufacturing the anthelminthic Azinox
      (biltricide) using the new interfacial transfer catalyst benzyl-di-propyl (beta
      hydroxyethyl)ammonium chloride. Azinox has been shown to be identical to
      biltricide (praziquantel) in its properties. Azinox tests on models of
      Opisthorchis felineus in golden hamsters and of Hymenolepis nana in albino
      outbred mice have indicated that the agent is not inferior to biltricide in its
      antitrematodal and anticestodal activities. Azinox displayed a high activity at
      the preimaginal stages of O. felineus and H. nana and at the larval stage of
      H.nana.

PMID- 9026674
TI  - [A dry nutrient medium for the cultivation of Leishmania promastigotes].
AB  - A dry medium formulation which provides the growth and reproduction of Leishmania
      promastigotes was designed. The medium has been prepared by using nondietary
      protein raw material, it contains domestic-production ingredients of that in high
      supply. The nutrient basis of the medium is enzymatic peptone (a source of amine
      nitrogen). The growth factors of Leishmania (a yeast extract, vitamins, amino
      acids, a dry blood derivative), carbohydrates (an energy components of the
      medium), inorganic salts (a source of trace elements), which are selected in
      strictly defined quantitative ratios, meet the physiological requirements of
      Leishmania. The agent rules out the necessity of adding ex tempore blood, making
      the process for preparing the medium from the dry powder simple and easy-to-use.

PMID- 9026675
TI  - [Plague in Rostov Province (its history, epidemiology, epizootiology, control
      measures and prevention)].
AB  - In the first third of the twentieth century, the overgrazing of cattle in the
      eastern districts of the modern Rostov Province yielded deserts in the places of
      virgin steppes and created favourable conditions for the enlargement of an area
      for the small souslik, a main carrier of plague in the natural focus of the
      northwestern Caspian Sea Region. On the above territories, this gave rise to a
      new natural focus of plague. Its liquidation required many-year goal-oriented
      efforts of large collective bodies of plaguologists and great material costs. The
      settlements of small sousliks exist on the above territories today and the
      activation of a natural focus of plague in the adjacent Kalmykia generate a need
      for enhancing plague epidemiological surveillance in the eastern districts of the
      Rostov Province today.

PMID- 9026676
TI  - [The evaluation of the efficiency of operating purification installations in
      relation to intestinal parasitic agents].

PMID- 9026677
TI  - [Spontaneous mixed infection in rodents with Borrelia and Leptospira].
AB  - This study was performed in a natural ITBB focus located in Perm' region of
      Russia. In 1993-1995, 73 root voles (Microtus oeconomus), collected in the
      forests, were examined by means of inoculation of internal organs on BSK-II
      medium. Borrelia were found in 13 animals (17.8%). According to the results in
      RLFP analysis 11 isolates were classified as B. garinii, 1 as B. afzelii and 1 as
      mixture of B. garinii and B. afzelii. In one case Leptospira, which was
      identified by PFGE analysis as grippotyphosa serovar, was found simultaneously
      with B. garinii in the BSK-II culture from urinary bladder. Our data testify to
      the fact of existence of mixed foci of leptospirosis and borreliosis. Moreover,
      one animal may serve as a reservoir host simultaneously of two different
      spirochetal agents.

PMID- 9026678
TI  - [An analysis of the results of histological and histochemical research on the
      integumental tissues and the digestive system of nematodes of the suborder
      Strongylata after the use of anthelmintics].
AB  - The analysis of the action of various anthelmintics on the integuments and
      digestive system of Strongylate nematodes indicated that all the used agents
      caused varying structural disorders. The swelling of the cuticle and its
      detachment from the subcuticle occurred with the overwhelming majority of the
      anthelminths on the integuments of the Strongylate nematodes. The digestive
      system showed an ample epithelial vacuolation in the intestinal wall, as well as
      swelling and destruction in the mitochondria and endoplasmic reticulum. Almost
      all the used agent lowered the levels of glycogen and RNA in the tissue of
      Strongylate nematodes.

PMID- 9026679
TI  - [The functioning of foci of mixed tick-borne infections on Russian territory].
AB  - Based on the studies of behavioral variations in ixodes persulcatus ticks under
      the influence of their carried pathogens, the authors forward a hypothesis for
      that there is antagonism between Borrelia and tick-borne encephalitis virus in
      the vector. Experiments demonstrated that Borrelia-infected ticks had a lower
      viral sensitivity than did noninfected ticks. There was inhibited viral
      reproduction in the ticks with double infection. Evidence is presented for that
      the Borrelia-infected nymphal ticks display the specific behavioral and viral
      susceptible features that are physiologically peculiar to older Borrelia-free
      individuals. It is concluded that the prevalence of Borrelia in the populations
      of ticks in the foci of mixed infections is associated with their property to
      suppress viral reproduction in the Borrelia-infected ticks.

PMID- 9026680
TI  - [Comparative study of the efficiency of ultralente insulin and NPH insulin
      combined with sulfonylurea in type 2 diabetes patients with secondary tolerance
      to sulfonylurea. Possible selection criteria].
AB  - The treatment of NIDDM patients with secondary failure to sulfonylureas is still
      a debated problem. In this study we compared in NIDDM patients with secondary
      failure to glyburide, the effect of adding a single, low-dose bed time either NPH
      or ultralent insulin injection (0.15-0.2 U/kg) to the previously ineffective
      sulfonylurea treatment. Both NPH and ultralent insulin therapy have been
      demonstrated to be effective in ameliorating metabolic control in NIDDM patients
      with secondary failure to sulfonylureas. However, the addition of bed-time
      ultralent insulin caused a greater and significant decrease in post prandial
      plasma glucose. In contrast, the average fasting plasma glucose decrease was
      significantly greater after NPH insulin administration. These results indicate
      that in NIDDM patients with secondary failure to glyburide bed-time ultralent
      insulin administration is a better tool to improve the post prandial plasma
      glucose.

PMID- 9026681
TI  - [Effect of sex on the increase of GH induced by galanin, alone or in combination
      with GHRH with or without pyridostigmine in pubescent subjects].
AB  - Growth hormone response to galanin (GAL) and growth hormone releasing hormone
      have been demonstrated to be higher in females than in males, and moreover the
      cholinergic system appears to be able to enhance them. On the basis of this
      presumption, we evaluated the GH response (expressed as area under the curve: AUC
      GH) to galanin (GAL, 10 mg/kg i.v.) or GHRH (1 mg/kg i.v.) either alone or
      associated together and with pyridostigmine (PD, 60 mg p.o.), and to saline
      infusion as a control, in 5 males and 5 females, in puberty, aged 16 +/- 0.4
      years old (mean +/- SD). In females tests were performed during the follicular
      phase of the menstrual cycle. GAL alone cannot provoke a response from GH unless
      associated with GHRH. The contemporary administration of PD does not increase the
      extent of the response. The latter did not differ between sexes. The GHRH-GAL
      association induced a higher response in GH compared to GAL alone and GAL-PD,
      without any differences between the sexes. Lastly, the combination GHRH-GAL-PD
      induced responses that were comparable to GHRH and GAL alone. Therefore GAL does
      not act alone but enhances the effect of GHRH and the cholinergic system appears
      to be involved as a modulator. Moreover, the effect of GAL is comparable in both
      sexes.

PMID- 9026682
TI  - [Evaluation of the role of repeat needle biopsy in the diagnosis and follow-up of
      thyroid nodules].
AB  - The goal of the present study was to determine in what percentage of cases was an
      initial benign cytological diagnosis modified to malignant or suspicion of
      malignancy by a second aspiration biopsy. The study group consisted of 708
      patients, 98 males and 610 females, mean age 46.3 +/- 13.7; FNB was always
      repeated on the same nodule. The first FNB (cytology I), classified the nodule
      as: non-diagnostic (group I, 205 cases) or diagnostic (group II, 503 cases);
      these latter were classified as benign (471) or suspect (32). In 82 cases of
      group I the second examination after six months (cytology II) was still unable to
      arrive at a diagnosis; in the remaining 123 cases, it was able to classify 120 as
      benign and 3 as suspect (the latter being followed up by diagnostic surgery). In
      group II, cytology II modified the initial diagnosis from benign to suspect (8
      cases) or non-diagnostic (7 cases). On the other hand, 29 cases had a change of
      their initial diagnosis from suspect to benign. The remaining cases of group II
      repeated a thyroid FNB after one year (cytology III) with a result of benign
      (486) or non-diagnostic (6). In the 14 cases followed up by diagnostic surgery,
      due to a second biopsy diagnosis of suspicion, histology showed the presence of
      Follicular Adenoma in 12 cases and Hashimoto's Thyroiditis in the remaining 2.
      Based on follow-up surgery, the suspicious lesions seen on the second biopsy
      turned out to be all non-malignant. However, it is important to underline the
      greater number of cases where the second examination gave a benign diagnosis when
      the first examination was judged suspicious. One can conclude that it may be
      useful to repeat FNB: 1) when the first exam resulted in an inadequate sample, as
      a second biopsy allows one to classify the nodule 60% of the time; 2) in all
      cases where there is an initial benign diagnosis, when non-surgical follow-up
      (clinical and/or echographic) is suspicious.

PMID- 9026683
TI  - [Blood glucose and insulin responses to oral glucose in hyperthyroidism].
AB  - Because thyroid hyperfunction "per se" can induce impaired glucose tolerance in 2
      57% of patients, we have studied glycaemic and insulinaemic response to oral
      glucose load (OGTT) in this condition. Glycaemic and insulinaemic curves after
      oral glucose (100 g), the respective secretory areas (AUC-G and AUC-IRI) have
      been determined in 13 hyperthyroid patients (8 Graves disease, 4 multinodular
      toxic goiters and 1 Plummer's adenoma) and in 16 healthy control subjects. AUC-G,
      AUC-IRI and median values of G and IRI in most of considered times have resulted
      significantly greater in hyperthyroid patients. This study has confirmed the
      impact of thyroid hyperfunction on carbohydrate metabolism, but has not proved an
      impaired insulin secretion as previously reported in Literature. In conclusion,
      we believe that: a) hyperthyroidism is associated with greater circulating levels
      of G and IRI, b) hyperinsulinaemia in addition to hyperglycaemia suggests that
      insulin-resistance is underlying in this condition.

PMID- 9026684
TI  - [Pancreatic beta-cell hyperplasia in adults. A clinical case].
AB  - The author describe a rare case of pancreatic beta-cell hyperplasia. The patient
      was referred to us because of serious hypoglycemic crises. During
      hospitalization, endogenous hyperinsulinism was confirmed by hematochemical and
      instrumental tests. AngioCT of the pancreas evidenced a small lesion of the
      corpus, suspected of insulinoma. The patient underwent a corpus caudalis
      pancreatectomy: a small nodule with histologic neuroendocrine traits was ablated.
      A few days after the operation, new symptomatic hypoglycemia appeared. The
      hormonal tests confirmed a recurrence of endogenous hyperinsulinism. The patient
      underwent a new operation for pancreaticoduodenectomy: histological examination
      confirmed a pancreatic beta-cells hyperplasia. This condition has to be taken
      into account in the differential diagnosis of post prandial hypoglycemia.
      Besides, the observation of an insulinoma doesn't exclude the presence of a
      diffused disorder of islet cells as in the case above described.

PMID- 9026686
TI  - [The preoperative treatment of patients with heart valve prostheses undergoing
      oral and maxillofacial surgical interventions. Our protocol].
AB  - The paper examines the prevention of hemorrhagic and bacterial endocarditis in
      patients with a prosthetic heart value and treated with oral anticoagulant
      therapy, undergoing oral and maxillo-facial surgery. The authors present a
      protocol personally adopted in hospital activity underlining the excellent
      results.

PMID- 9026685
TI  - [Transient hypocalcemia after thyroidectomy].

PMID- 9026687
TI  - [The dental assessment of the patient waiting for a liver transplant].
AB  - Until the last several years liver transplantation was considered an experimental
      treatment procedure. Nowadays virtually any disease process, that is in terminal
      stage, is treatable with transplantation. The introduction of cyclosporine in
      1980 and the recent use of OKT3 monoclonal antibody now allows a 5-year survival
      rate of 60-70%. The causes of early death of patients who survive after surgery
      are infective complications, multiorgan failure and acute rejection of the
      allograft. In the literature and in our experience, bacterial sepsis is the most
      common cause of deaths occurring during the first postoperative months while most
      deaths after one year are generally related to chronic rejection of the
      allograft. The risk of infection is also increased by the over-immunosuppression
      of these patients always treated with a high dose of immunosuppressive agents
      when evidence of acute graft rejection is found. Regarding these problems,
      patients being prepared for liver transplantation should be evaluated for their
      dental health. The medical indications of 80 transplant recipients and the
      current status of liver transplantation are reviewed in this article. We describe
      the dental status of these patients that should receive indicated dental care
      before surgery. Most patients (90%) were affected by chronic active hepatitis
      while the number of primitive cirrhosis was significantly lower. Very poor dental
      hygiene was found in 85% of patients while 45% were affected by advanced
      periodontal disease and 12% by a chronic gingivitis. Dental caries were observed
      in 67% while in 20% of cases endodontic periapical lesions were found and only 2%
      of these resulted as radicular cysts. Indicated dental care consisted in 87% of
      cases in dental hygiene instructions, in 85% in scaling and root planing, in 63%
      in conservative restorations and in 40% in endodontic treatments. Dental
      treatment guidelines before transplantation are described with particular
      attention to prevent risk of infection using antibiotic prophylaxis for invasive
      dental procedures. Dentists, after surgery must be also prepared to deal with
      excessive bleeding related to a severe liver disfunction; for this purpose an
      appropriate protocol is also described. The monitoring of oral and general health
      conditions and the achievement of specific protocols of prophylaxis are helpful
      in the prevention of complications and are fundamental to obtain the best results
      with liver transplantation improving the quality of life of these patients.

PMID- 9026688
TI  - [Histological study of synchondroses and of the nasal capsule in the human fetal
      cranium].
AB  - The aim of this paper is to describe the development and growth of the middle
      line cranial base synchondrosis and nasal septal cartilage of human fetuses. The
      sample consisted of 25 human fetuses aged from 9 weeks to 6 months. The samples
      were decalcified and processed in paraffin. Sections were cut at 10 mu and
      stained with Mallory staining. Histomorphological observation pointed out the
      presence and development of cranial base synchondrosis and nasal septal
      cartilage. As far as synchondrosis cell zone layers in endochondral growth sites
      are described moreover a caudorostral gradient in growth rate was observed.
      Functional connexions between the cartilaginous nasal capsule and the developing
      maxillae and premaxillae have been examined. The main connection was found to
      consist of the anterior septopremaxillary ligament running from the anterior
      border of the nasal septum posteroinferiorly to blend with premaxillary
      periosteum and interpremaxillary suture.

PMID- 9026689
TI  - [Oral candidiasis following radiotherapy for neoplasms of the oromaxillofacial
      area].
AB  - The authors report the clinical and histopathologic factors of oral candidiasis
      in patients treated with irradiation for head and neck cancer and predisposing
      antimycotic related treatments.

PMID- 9026690
TI  - [Pemphigoid of the mucous membranes. The clinical, histopathological and
      immunological aspects and current therapeutic concepts].
AB  - Mucous membrane pemphigoid (MMP) is a chronic disease of unknown etiology
      frequently involving oral cavity and eye and sometimes also pharyngeal,
      laryngeal, oesophageal and genital mucosae. It is characterized histologically by
      a sub-epithelial blister and by a typical direct immunofluorescence feature
      showing linear binding of IgG and C3 to the basement membrane zone (BMZ). The
      predominance of mucosal involvement or the lack of skin lesions distinguish MMP
      from bullous pemphigoid. Oral mucosal presentation of MMP is quite variable from
      chronic erythematous lesions to erosions covered by a fibrinous slough produced
      by bullae rupture involving mainly gingiva, buccal mucosa and palate. Because eye
      manifestations of MMP are common and blindness may develop, an ophthalmological
      examination is mandatory in these patients, although recent data suggest that
      pure ocular pemphigoid, oral pemphigoid and MMP with cutaneous lesion could be
      different diseases. Further immunological and biochemical studies are needed to
      better characterize these pathologies. It is generally considered that blister
      formation in MMP is the result of immunoglobulin deposition leading to complement
      activation in the BMZ, but there are not specific pathogenetic data regarding
      oral pemphigoid. Multiple therapeutic options exist including topical and
      systemic corticosteroids associated or not to other immunosuppressive drugs,
      dapsone and tetracycline but there do not exist treatment modalities generally
      accepted.

PMID- 9026691
TI  - [Brown tumor of the jaws].
AB  - Brown tumour is one of the forms in which fibrous-cystic osteitis, which
      represents the terminal stage of the bone remodelling processes during primary or
      secondary hyperparathyroidism, is manifested. For years brown tumour was regarded
      as a typical lesion of primary hyperparathyroidism, but cases of brown tumours in
      patients with hyperparathyroidism secondary to renal failure were increasingly
      often reported in the literature. From an epidemiological point of view, the
      frequency of brown tumours in patients with renal insufficiency is extremely
      variable, as is the bone site affected. Several bone segments can be affected at
      once, but the ethmoid and frontal sinus are rarely reported. Symptoms are caused
      by the considerable dimensions of the brown tumour and its localisation: in the
      jawbones it may present sometimes painful, hard and clearly palpable swellings;
      if large, the tumour may deform the appearance of the bone segments affected or
      alter the function of the masticatory apparatus. In other cases, there is a
      complete absence of clinical symptoms and diagnosis may be totally coincidental
      during the radiological examinations. In histological terms, brown tumours are
      made up by a cell population consisting of rounded or spindle-like mononucleate
      elements, mixed with a certain number of plurinucleate giant cells, resembling
      osteoclastic cells, among which recent haemorrhagic infiltrates and hemosiderin
      deposits (hence the brown colour) are often found. The aim of this study was to
      report three cases from a population of 107 patients undergoing haemodialysis at
      the Turin University Centre. In conclusion, the localisation of maxillary brown
      tumours appears to prefer a young, female population; brown tumours are rarely an
      early sign of hyperparathyroidism in haemodialysis patients, but they often
      appear in conditions of advanced hyperparathyroidism which have escaped medical
      control either owing to unsuitable therapy or scant patient compliance; they are
      rapidly evolving lesions whose regression may be very slow or not occur even
      after total parathyroidectomy; the severity of the lesion caused by a brown
      tumour may lead to evident osteolysis in the maxillofacial district, thus
      suggesting the need for early and regular radiological screening; in the event of
      lesions which are already present, from the authors' point of view, the choice of
      treatment must be oriented towards parathyroidectomy.

PMID- 9026692
TI  - [Adenophlegmons of the neck area. A case report and review of the literature].
AB  - Adenopathies in general and cervicofacial adenopathies in particular are a
      pathology that can affect both medical and surgical disciplines. They may be
      found in both acute and chronic disorders, in children and in adults, and in
      local or systemic forms with benign or malignant pathogenesis. It is clear that
      the differential diagnosis and consequently the therapeutic approach may be
      complicated at times by the variety of pathological processes. Interest in the
      case reported her is, in our opinion, justified by the rare finding in the age of
      antibiotics of such striking symptoms. The severity of local symptoms and the
      general conditions of the patient resulted in the need for surgery under
      anesthesia in order to enable the extensive collection of purulent matter to be
      drained. The postoperative course showed a marked and progressive improvement of
      the patient's general and local conditions, even a few hours after surgery. Given
      that several factors contribute to determining the evolution of septic conditions
      (patient's general and in particular immunological status) and given that, owing
      to the aspecific nature of symptoms, the diagnosis and relative specific therapy
      may be delayed, it can be seen that the clinical picture may evolve and be
      complicated by massive general manifestations, sufficient in extreme cases to
      endanger the patient's life, in the form of acute and sudden respiratory
      disorders and or more gradually with generalised septic conditions (encephalitis,
      mediastinitis and generalised sepsis). The objective to be attained is therefore
      a careful diagnosis and the immediate implementation of medical procedures in
      order to remove the cause that has triggered off the pathology.

PMID- 9026693
TI  - [Traumatism of the orbital-eyelid area].
AB  - The anatomical characteristics of the orbital-eyelid region are responsible for
      many traumas of different kinds, like road, domestic and sports accidents,
      especially in the last years. Therefore different kinds of lesion of the soft and
      hard tissues in the orbital region and the diagnoses and the therapeutics
      according to plastic and maxillo-facial surgery are examined.

PMID- 9026694
TI  - [An XPS and SEM study of the chemical-micromorphological characteristics of the
      dentin-resin adhesive interface. I].
AB  - In this preliminary note the author examined the chemical characterisation of
      dentin surfaces after treatment with an acid conditioner (nitric acid), using the
      XPS and Auger techniques, to evaluate whether micromorphological variations
      already reported by other authors are associated with changes of a chemical
      nature. The results of this study show an alteration of the superficial chemical
      component of dentin following treatment with the conditioner that would enable
      the realisation of closer binding with composite materials.

PMID- 9026695
TI  - [The measurement of orbital volume in reconstruction of the orbital walls].
AB  - Before reconstruction of the orbital walls and other surgical procedures
      involving the orbits leading to a modification of pathologically altered orbital
      volumes, it is useful to measure these volumes in order to allow a more precise
      correction. Orbital volumetric studies on 22 patients and 6 dry skulls were
      performed using high resolution computer tomography. Fourteen patients presented
      enophthalmos of various origin, 3 patients fibrous dysplasia involving the orbits
      and 5 patients showed orbital pathology. In 10 patients with unilateral post
      traumatic enophthalmos an increase of the bony orbital volume of 20.1% in the
      average was found corresponding to an enophthalmos of 3.5 mm in the average.
      Correlation between the severity of the enophthalmos and the increase in orbital
      volume was found. Enophthalmos could not be correlated to the intraorbital fat
      volume, especially no atrophy of orbital fat could be demonstrated in these
      patients. Normal orbital volume measurements of patients and dry skulls were
      compared to those found in the literature. Planning of the surgery was therefore
      facilitated before correction of enophthalmos, reconstruction of bony orbital
      contour after tumor-resection and in patients with fibrous dysplasia. Results
      suggest that the bony enlargement, followed by a change in soft-tissue shape and
      position is the usual cause of posttraumatic enophthalmos. Changes in volume of
      soft-tissues themselves are less significant.

PMID- 9026696
TI  - [Oral lichen planus (OLP). Therapeutic guidelines and clinical experience with 71
      patients].
AB  - The authors report the results of a study performed in 71 patients suffering from
      lichen planus of the mucous membranes and skin. They discuss dermatological and
      stomatological clinical data in relation to possible basal diseases
      (hepatopathies, dermopathies, diabetes, hypertension, gastrointestinal diseases,
      etc.) and other anamnestic data (psychological aspects, drug taking, working
      activity, etc.). Moreover, they report the results of the clinical protocol used
      (betamethasone in a gel and vitamin A base) with a follow-up of 5 years and
      examine the other therapeutic possibilities reported in the literature.

PMID- 9026697
TI  - [Surgery of lower third molars and lesions of the lingual nerve].
AB  - OBJECTIVE: The authors describe a technical expedient applied during the removal
      of totally or partially impacted lower third molars, in order to prevent lingual
      nerve damage. EXPERIMENTAL ASSAY: Retrospective study. MATERIALS AND METHODS: The
      sample includes 1835 extractions of totally or partially impacted lower third
      molars, performed on 1030 patients, 493 males and 537 females, aging between 12
      and 72 years. All the operations were carried out under local anaesthesia with
      standardization of the surgical protocol. A mucoperiosteal paramarginal flap was
      used in case of germectomy, whereas a mucoperiosteal marginal flap with mesial
      releasing incision was used in case of fully mature teeth. Ostectomy and tooth
      sectioning were performed using a round and fissure bur respectively, assembled
      on a straight low-speed handpiece and under irrigation with sterile saline.
      RESULTS: The authors reported only one case of transient lingual nerve
      paresthesia (0.05%) which occurred in a 19-years old female presenting a totally
      impacted third molar mesial-lingual inclination. Symptoms disappeared
      spontaneously one week postoperatively. Therefore the overall incidence of
      permanent nerve damage was equal to 0%. CONCLUSIONS: The data reported in
      literature show a lingual nerve lesion incidence ranging between 0% and 22%. With
      this simple surgical expedient the incidence of permanent lingual damage was 0%.
      Thus, it is the authors' opinion that this simple expedient should be applied in
      all cases of impacted third molar removal.

PMID- 9026698
TI  - [Gingival hypertrophy due to cyclosporine. A review of the literature].
AB  - Cyclosporine is now the elective drug for immunosuppressive treatment in organ
      transplant patients. Compared to traditional immunosuppressants this molecule
      offers the therapeutic advantage that it does not act indiscriminately on all
      components of the immune system. In addition to the primary pharmacological
      action, cyclosporine also presents a number of undesirable effects, among which
      it is worth mentioning short and long-term nephrotoxicity and the development of
      neoplasia, in particular lymphomas. Other undesired effects of the drug are the
      possibility of overinfection, thrombosis, hypertension, hypertrichosis,
      hepatotoxicity and the development of the hypertrophic and hyperplastic gingival
      pathology.

PMID- 9026699
TI  - [Polyostotic fibrous dysplasia. A clinical case report].
AB  - The authors present a severe case of polyostotic fibrous dysplasia in which there
      was considerable involvement of cranial bone and facial skeleton. Numerous
      lesions were present at the level of the long bones of limbs. Endocrine
      dysfunction was also present in the form of a hypophyseal adenoma secreting
      prolactin and ACTH. The concomitance of acromegaly or gigantism and/or
      hyperprolactinemia and polyostotic fibrous dysplasia has only been reported to
      date in a few cases in literature. The authors describe the appearance of the
      subject, correlating clinical photographs with X-rays. They report the clinical
      excursus of the patient characterised by the gradual increase in deformities
      which seriously jeopardized the patient's relational life, in particular the
      appearance of a bulk on the forehead and checks and the deformation of the
      symphyseal portion of the mandible with presence of interdental diastemata. The
      patient also complained diplopia, difficulty in chewing owing to the mobilisation
      of teeth, and increasing bone pain probably due to nerve compression by exuberant
      bone. It was not possible to perform corrective surgery owing to the patient's
      overall poor health conditions. In fact, dilatative cardiomyopathy which
      continued to worsen in spite of numerous forms of medical treatment resulted in
      the patient's death owing to cardiac decompensation. Even the attempt to treat
      the patient's primary endocrine dysfunction using bromocryptine and subsequently
      octreotide failed to produce positive results owing to the onset of collateral
      effects which led to the early suspension of treatment.

PMID- 9026700
TI  - [Radiological considerations of malpractice in dentistry].
AB  - Several branches of competence are needed to evaluate malpractice in dentistry:
      first a complete case history, secondly careful clinical observation and finally
      a correct procedure of radiographic documentation. This latter is able to prove
      existence of the treatment and its evolution, moreover it shows the bone, the
      dental components underneath the surface and the treatment becomes appraisable by
      different observers. In restorative dentistry, radiological findings allow us to
      demonstrate overcontoured restorations in approximal sites and, if necessary,
      identify the biological width. In endodontics the insufficient filling or the
      overfilling of the root channel can be demonstrated along with the material used
      for the filling and the presence of fractured instruments inside the channel. In
      prosthodontics, on the other hand, the quality of the abutments, fractured roots
      and/or prosthesis, symptoms of inadequate charge on the bone and overcontours
      with the subsequent periodontal damage can be seen. In orthodontics one can
      assess the appearance of infrabone pockets, reabsorptions and horizontal
      recessions. In extractive surgery it is again possible to identify through
      radiographic documentation small root fragments in the maxillary sinus (possible
      sinusitis associated) and maxillary fractures as a consequence of extractions. In
      the field of implantology, damage to noble structures due to inadequate case
      planning can be highlighted.

PMID- 9026701
TI  - [Periapical lesions of mixed etiology: bacterial and foreign body].
AB  - After a review of the literature on periapical lesion pathogenesis, we studied
      histological, immunological, and bacteriological examinations of 10 overfilled
      teeth with periapical lesions. We found, in our research, a bacteriological
      etiology with foreign body reactions.

PMID- 9026702
TI  - [The role of SMAS in the prevention of Frey's syndrome].
AB  - Frey's syndrome is the most common postoperative complication in the parotid
      gland surgery. The authors report their own experience with 80 patients who
      underwent surgical operation of superficial or total parotidectomy. In 45 of them
      was performed the SMAS flap, no SMAS flap performed in the remaining 35 patients.
      The follow-up was performed by interviewing the patients about their symptoms.
      The purpose of this work is to show the role of SMAS flap, that minimize the
      frequency and the intensity of symptoms of the Frey's syndrome.

PMID- 9026703
TI  - [The role of the traditional radiological methods in conservative therapy and
      endodontics].
AB  - The traditional radiographic examinations used in restorative dentistry and
      endodontics are: intraoral radiograph performed in the beta-wing or the
      paralleling technique, the partial extraoral radiograph (rotational narrow beam),
      the panoramic radiography and the periapical radiographs with the bisecting
      technique which is particularly suitable for visualization of the apex. Radiology
      is a valuable diagnostic means to evaluate the extension of primary caries, to
      identify secondary and interproximal initial decays and if required let the
      therapist measure the biological width. Several factors influence the
      radiographic interpretation of caries: cervical burnout, mach band effect,
      internal and external resorption, restorative materials for fillings and sub
      bases, abrasions and/or erosions. Radiology allows the diagnosis of developmental
      and acquired abnormalities of the teeth which can have an influence on the
      treatment itself. Examples are: variations in the shape of the crown and root,
      dens in dente, enamel hypoplasia, dentinogenesis imperfecta. Radiograms are of
      major importance in the evaluation of restorative dentistry results: precision of
      the margins, congruous contact points, fractures. Moreover, it provides the
      endodontic procedures with useful diagnostic data and permits the measurements
      during the treatment, supplying the immediate and long term checks too.

PMID- 9026704
TI  - [Globulomaxillary cysts].
AB  - Globulomaxillary cyst is a non odontogenic cyst arising in the upper lateral
      incisor and canine region. Evaluation of clinical picture and careful histologic
      examination are essential for distinguishing it from other odontogenic and non
      odontogenic cystic growths. Presenting five new cases of globulomaxillary cysts,
      authors discuss and accept the "fissural" histogenetic hypothesis.

PMID- 9026705
TI  - [Mucoepidermoid carcinoma and mucoepidermoid cyst of the jaw bones in the same
      patient. A clinical case and discussion of their histogenesis].
AB  - The association between a so-called mucoepidermoid cyst and a central
      mucoepidermoid carcinoma in a 29-year-old man is reported. Since the two lesions
      are in continuity and the morphologic appearances are very much alike, a close
      relationship between these entities is suggested.

PMID- 9026706
TI  - [Warthin tumor of the palate: an unusual location].
AB  - Warthin's tumor (papillary cystadenoma lymphomatosum) primarily involves the
      parotid gland, whereas localization in the palate has been reported by a few
      authors. A new case of true Warthin's tumor arising from the hard palate is here
      presented and histogenesis and differential diagnosis are briefly discussed. CASE
      REPORT: A 50 year-old woman who was referred to us because of the presence of
      multiple contiguous bluish cyst-like lesions involving both sides of the hard
      palate mucosa. The lesion was removed with a wide excision involving almost all
      the soft tissues of the hard palate. Histologic diagnosis (E.E stain) was:
      papillary cystadenoma lymphomatosum. DISCUSSION AND CONCLUSION: The histogenesis
      of Warthin's tumor is still controversial. The most widely accepted theory is
      that the tumor represents a neoplastic proliferation of salivary gland ducts
      entrapped in pre-existing lymph nodes. In fact, immunohistochemical analysis and
      cell-surface markers studies have shown that the lymphoid component is
      predominantly formed by T-lymphocytes, with a relatively small number of
      polyclonal B-lymphocytes. On the contrary, other authors found opposite
      relationship between T and B lymphocytes. These findings supported the concept
      that lymphoid tissue in Warthin's tumor represented a reactive cellular
      infiltrate in a pattern similar to that seen in reactive lymph nodes. Similar
      results have been found in this report; moreover, the hard palate does not
      usually contain lymphatic tissue. This could support the idea that the lymphoid
      tissue associated with this case is reactive and a direct origin from the ductal
      epithelium with secondary lymphocytic infiltration is more likely to occur in
      this area.

PMID- 9026707
TI  - [The departmental concept in the therapy of facial dysmorphisms. A preliminary
      note on the psychological aspects].
AB  - The authors describe the work carried out with the intention of map and border in
      simple and repeatable way the risk of dissatisfaction in the patient candidates
      to cosmetic and oro-maxillo-facial surgery. It represent the first of a series of
      notes which propose to characterize patients with problems tied to the
      organization of the individuality in which, the discrepancy among expectations
      and obtained result, lead in the more serious cases, to a real crisis of identity
      or a depressed state of varied entity.

PMID- 9026708
TI  - Poliomyelitis prevention in the United States: introduction of a sequential
      vaccination schedule of inactivated poliovirus vaccine followed by oral
      poliovirus vaccine. Recommendations of the Advisory Committee on Immunization
      Practices (ACIP)
AB  - These revised recommendations of the Advisory Committee on Immunization Practices
      (ACIP) replace recommendations on poliomyelitis issued in 1982 and 1987, and
      present a new ACIP poliovirus vaccination policy that increases reliance on
      inactivated poliovirus vaccine (IPV). This change in policy is the most
      substantive since the introduction of oral poliovirus vaccine (OPV) in 1961. ACIP
      has determined that the risk-benefit ratio associated with the exclusive use of
      OPV for routine immunization has changed because of rapid progress in global
      polio eradication efforts. In particular, the relative benefits of OPV to the
      U.S. population have diminished because of the elimination of wild-virus
      associated poliomyelitis in the Western Hemisphere and the reduced threat of
      poliovirus importation into the United States. The risk for vaccine-associated
      poliomyelitis caused by OPV is now judged less acceptable because of the
      diminished risk for wild-virus-associated disease (indigenous or imported).
      Consequently, ACIP recommends a transition policy that will increase use of IPV
      and decrease use of OPV during the next 3-5 years. The revised recommendations
      include three options for poliovirus vaccination, all of which meet acceptable
      standards of care: sequential vaccination with IPV followed by OPV, OPV alone, or
      IPV alone. For overall public health benefit, ACIP recommends a sequential
      vaccination schedule of two doses of IPV followed by two doses of OPV for routine
      childhood vaccination. Vaccination schedules that include OPV alone or IPV alone
      are also acceptable and are preferred in some situations (e.g., IPV alone is
      recommended for children who are immunosuppressed; OPV alone is preferred for
      children who begin the primary vaccination schedule after 6 months of age).
      Implementation of these recommendations should reduce the risk for vaccine
      associated paralytic poliomyelitis and facilitate a transition to exclusive use
      of IPV following further progress in global polio eradication.

PMID- 9026709
TI  - Respiratory infection--Pennsylvania. 1977.

PMID- 9026710
TI  - Follow-up on respiratory illness--Philadelphia. 1977.

PMID- 9026711
TI  - Prevalence of cigarette smoking among secondary school students--Budapest,
      Hungary, 1995.
AB  - Because of the high prevalence of tobacco use in countries of Central and Eastern
      Europe, public health officials in many of these countries have designated as a
      priority the prevention of smoking initiation among youth. In 1995, a nationally
      representative survey in the Republic of Hungary documented that 35.8% of 16-year
      old students in that country had smoked cigarettes during the preceding 30 days.
      To better characterize smoking among youth in Hungary, the Field Epidemiology
      Training Program, Hungarian Ministry of Welfare, conducted a cross-sectional
      survey in Budapest (1995 population: 1,906,798) among secondary school students
      aged 14-18 years. Specific objectives of the survey were to assess the prevalence
      of cigarette smoking among these students, determine factors associated with
      higher prevalences, and describe the smoking habits of current cigarette smokers.
      This report summarizes the findings, which indicate that one third of all
      students smoked; half of all 18-year-olds smoked; and of those students who
      smoked, 41% most frequently smoked an imported, internationally recognized
      cigarette brand.

PMID- 9026712
TI  - Outbreaks of pneumococcal pneumonia among unvaccinated residents of chronic-care
      facilities--Massachusetts, October 1995, Oklahoma, February, 1996, and Maryland,
      May-June 1996.
AB  - During October 1995-June 1996, CDC and state and local public health agencies
      investigated outbreaks of pneumococcal pneumonia with bacteremia at chronic-care
      facilities (CCFs) serving predominantly elderly populations in Massachusetts,
      Oklahoma, and Maryland. This report summarizes these investigations and
      identifies measures that may prevent such outbreaks.

PMID- 9026713
TI  - Antibiotic resistance among nasopharyngeal isolates of Streptococcus pneumoniae
      and Haemophilus influenzae--Bangui, Central African Republic, 1995.
AB  - Approximately 4 million children aged < 5 years die worldwide each year from
      acute respiratory infections (ARI), most of which are pneumonia. Most pneumonia
      deaths result from bacterial infections, and Streptococcus pneumoniae (SP) and
      Haemophilus influenzae (HI) are the most common bacterial etiologies. To provide
      data about antibiotic resistance and to assist the National ARI Control Program
      of the Central African Republic (CAR) (1995 population: 2.9 million) in choosing
      which antibiotics to recommend for the treatment of pneumonia in children aged <
      5 years, a survey of the antibiotic resistance of nasopharyngeal (NP) isolates of
      SP and HI cultured from children residing in Bangui (1995 population: 451,000),
      CAR, was conducted during January 16-February 8, 1995, by the Ministry of Public
      Health and Population (MOPHP) in collaboration with epidemiologists from CDC and
      microbiologists from the South African Institute for Medical Research. Bangui is
      the capital of and the largest city in CAR. The decision to measure resistance
      rates among NP isolates was based on the results of a study indicating that
      resistance rates of SP and HI isolates cultured from NP swabs were similar to
      rates measured among isolates cultured from blood. This report summarizes the
      results of that survey, which indicated that SP and HI had relatively low
      resistance rates to penicillin, ampicillin, cotrimoxazole (trimethoprim
      sulfamethoxazole), and chloramphenicol.

PMID- 9026714
TI  - [Polyribozymes].

PMID- 9026715
TI  - [Problems in the study of structure and expression of milk protein genes].

PMID- 9026717
TI  - [Cloning of DNA probes for detection and identification of pathogenic fungi
      Verticillium dahliae i Verticillium tricorpus].

PMID- 9026716
TI  - [N.BstSE--a site-specific nickase from Bacillus stearothermophilus SE-589].

PMID- 9026718
TI  - [Analysis of allelic polymorphism of two tetranucleotide tandem repeats in two
      urban populations in Russia].

PMID- 9026719
TI  - [Molecular mechanisms of the regularity of nucleic acid biosynthesis. Computer
      study of the role of polymerases in the formation of irregular pairs by modified
      bases].

PMID- 9026720
TI  - [Expression of a hybrid protein between human gamma-interferon and alpha
      fetoprotein in E. coli cells].

PMID- 9026721
TI  - [SegE endonuclease from T4 phage. II. Determination and characteristics of
      recognition site].

PMID- 9026722
TI  - [Molecular phylogeny of planarians (Turbellaria, Tricladida, Paludicola) from the
      lake Baikal. Use of comparative analysis for determination of nucleotide sequence
      of 18S ribosomal RNA].

PMID- 9026723
TI  - [mRNA for tissue-type plasminogen activator in various human tissues and organs].

PMID- 9026724
TI  - [The gene for Duchenne muscular dystrophy is organized into several replicons].

PMID- 9026725
TI  - [Approaches to identification of recombination-active DNA sites in human genome].

PMID- 9026726
TI  - [Construction and synthesis of beta-hairpins capable to recognize DNA nucleotide
      sequences].

PMID- 9026727
TI  - [Heterogeneous complexes of ethidium bromide and their role in the stabilization
      of the (dA)n.(dT)n-structures].

PMID- 9026728
TI  - [A study of kinetics of endonuclease reactions using flow linear dichroism
      technique].

PMID- 9026730
TI  - [Isolation of catalytically active subunit of protein kinase from a complex form
      of DNA-polymerase alpha in the rat liver using electrofractionation in denaturing
      conditions].

PMID- 9026729
TI  - [Differential effect of glucosaminylmuramyl dipeptide on the phenotype of
      melanoma sublines with different metastatic potential].

PMID- 9026731
TI  - [A novel version of PROF_PAT 1.0 data bank of protein families: technology of
      formation nad rapid search programs].

PMID- 9026732
TI  - [Ribozyme cleaving the mRNA for influenza virus type A polymerase gene].

PMID- 9026733
TI  - Proceedings of the 6th International Symposium on Immunological and Clinical
      Problems of Food Allergy. Lugano, Switzerland, September 24-26, 1995.

PMID- 9026734
TI  - [Hypertension in children; forgot to measure it].

PMID- 9026735
TI  - [Reflections on hypertension in relations to 100 years of Riva-Rocci].

PMID- 9026736
TI  - [Did hypertension diminish in The Netherlands between 1974 and 1993?].

PMID- 9026737
TI  - [The Nobel Prize Medicine 1996 for the discovery of MHC restriction].

PMID- 9026738
TI  - [Reinstatement of sodium restriction and diuretics in the treatment of
      hypertension].

PMID- 9026739
TI  - [Psychoneuroimmunology and breast cancer].

PMID- 9026740
TI  - [Variation in reporting of available places in the neonatal intensive care units
      and consequences for efficiency, fairness and quality of care].
AB  - OBJECTIVE: To determine whether the national information system on available beds
      in neonatal intensive care units (NICUs) leads to fair distribution and good
      efficiency and quality of care. SETTING: Two out of the ten NICUs in the
      Netherlands. DESIGN: Descriptive. METHODS: Data were gathered through
      observations and 18 interviews with among others neonatologists, gynaecologists
      and paediatricians. Another 19 doctors were interviewed by phone after a patient
      they had referred was refused. Interviews were analysed by means of Kwalitan, a
      computer programme for analysis of qualitative research. RESULTS: When a patient
      could not be admitted in his own region, the information system was often used to
      find out which NICUs had a bed available. Sometimes a NICU was called that,
      according to the information system, did not have a place available. Reasons
      were: the information was not up to date and not all available beds were
      reported. This last reason had to do with the wish to keep a bed free for
      patients from the NICU's own region. Because most doctors were aware of this,
      they sometimes negotiated about beds, which was time-consuming. CONCLUSION: The
      information system was used often, but was working below optimal level, resulting
      in diminished efficiency. This was primarily caused by the priority given to
      patients of the own region, which had to do with quality of care considerations.
      The existing variation in use of the priority policy deserves attention from the
      viewpoint of procedural justice.

PMID- 9026741
TI  - [Consensus on diagnosis and treatment of the lumbosacral radicular syndrome.
      Dutch Society for Neurology].
AB  - A consensus development meeting concerning the treatment of lumbosacral radicular
      syndrome (LRS) by entrapment by a herniated disc or spinal stenosis was held on
      June 9th, 1995. It was observed that there is a lack of good evidence on many
      aspects of diagnosis and treatment of LRS. Agreement was reached on the thesis
      that the natural course of LRS is often benign. Diagnosis and treatment can
      usually be left to the primary care physician. Specialist consultation and
      ancillary investigations are only needed if an operation is indicated or in case
      of persistent diagnostic uncertainty. If imaging is needed MRI is preferred to CT
      or myelography. MRI is highly sensitive, but less specific, and may thus give
      false-positive results. Neurophysiologic testing may be informative in selected
      cases. Plain spinal X-rays are not useful in most cases. The traditional non
      invasive treatments (such as bedrest, traction, physiotherapy, spinal
      manipulation) are not based upon convincing scientific evidence. Diagnostic
      imaging and invasive treatment should be considered in patients with a severe LRS
      that does not improve within a 4 to 8 week period. Both discectomy and
      chemonucleolysis are effective treatments. The principal indication is
      incapacitating radicular pain. There is no sound evidence that the prognosis of
      paresis is improved by operation. A cauda equina syndrome urgently needs surgical
      treatment. The efficacy of percutaneous interventions (nucleotomy, laser therapy)
      has not been proven. There are no strategies for the primary or secondary
      prevention of LRS that have demonstrated their efficacy. Psychological, social
      and financial factors probably contribute significantly to the occurrence of
      persisting symptoms after a LRS. Advice not to work after treatment for LRS may
      impede rehabilitation.

PMID- 9026742
TI  - [Incidence and treatment of prostatic carcinoma in the region of the
      Comprehensive Cancer Center Amsterdam, 1989-1994].
AB  - OBJECTIVE: To gain insight into the incidence and treatment of prostate cancer.
      DESIGN: Descriptive. SETTING: Comprehensive Cancer Centre Amsterdam, the
      Netherlands. METHODS: All prostate cancers diagnosed in 1989-1994 in residents of
      the region of the CCCA (North Holland and Flevoland) were selected from the
      regional cancer registry data base. Cases from one hospital were excluded due to
      incomplete registration. RESULTS: There was a 38% increase in the number of
      diagnosed prostate carcinomas between 1989 (n = 671) and 1994 (n = 929). Median
      age at diagnosis was 74 years. The proportion of localized tumours remained at
      the level of 69% during this period. The percentages of localized T1 tumours and
      tumours with unknown T stage decreased, while the percentages of localized T2 and
      T3 tumours increased. There was a sixfold increase in the number of total
      prostatectomies. 77% of the operated patients were diagnosed with a T2 tumour,
      11% with a T3 tumour. At the end of the study period total prostatectomy was the
      main treatment of T1/2 prostate cancers in men below the age of 60. T3 tumours
      and men between 60 and 75 years of age were more often treated with radiotherapy,
      while men over 75 were mainly treated hormonally. The percentage of localized
      prostate cancers observed strongly increased with age and with lower T stage.
      CONCLUSION: The sharp rise in the number of prostate cancers during the period
      1989-1994 was not confined to early stages. Within a few years total
      prostatectomy became one of the main treatment modalities in localized prostate
      cancer. This treatment was mainly restricted to younger men with smaller
      localized prostate carcinomas.

PMID- 9026744
TI  - [Living in injury time out?].

PMID- 9026743
TI  - [Hypertension caused by licorice consumption].
AB  - In a 38-year-old woman who was hospitalized because of hypertension and
      hypokalaemic alkalosis, the intake of liquorice (200 g per day) was proven to be
      the cause. A liquorice provocation test produced all the expected clinical and
      biochemical abnormalities. Some kinds of liquorice contain glycyrrhetic acid
      which inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase (e.g. in the
      kidney) leading to decreased transformation of cortisol into cortisone. The
      mineralocorticoid action of cortisol causes a drop in serum potassium and an
      increase in serum sodium concentration, together with a metabolic alkalosis,
      which in the patient described led to retention of water resulting in weight
      increase and hypertension.

PMID- 9026745
TI  - [Medical disciplinary jurisprudence in The Netherlands; a 10-year review].
AB  - OBJECTIVE: To obtain information about the nature and the number of complaints,
      the complainants and the accused health professionals and about the sanctions
      imposed by the Dutch medical disciplinary courts. DESIGN: Descriptive,
      retrospective study. SETTING: Inspectorate for Health Care, Rijswijk, the
      Netherlands. METHODS: All verdicts (n = 5333) given by the 5 medical disciplinary
      courts of first instance in the period 1983-1992 and the appeals arising from
      these verdicts were studied using the data of the Inspector in chief. These were
      related to the total number of practising clinicians obtained from the
      Inspectorate, the Royal Dutch Medical Association and Statistics Netherlands. The
      year of each verdict was noted, the number and nature of the verdicts, the
      categories of complainants and accused, the number of appeal cases and their
      consequences. RESULTS: The number of complaints doubled in the period under
      study, rising from 379 to 720 per annum. Most of the complaints (92%) were
      against doctors, but the number of complaints were divided very unevenly over the
      clinical specialists. A large number of the complaints concerned 'lack of care or
      inadequate care' (27%), or 'incorrect treatment' (22%). Of all complaints 20% led
      to a sanction, mostly a warning (62%). Appeals were lodged against 29% of the
      verdicts. In 22 cases the licence to practice was withdrawn definitively.
      CONCLUSIONS: Although the number of complaints increased over the study period,
      there was no reduction in the seriousness of the complaints. The effect of the
      disciplinary jurisdiction on the quality of care has not yet been adequately
      investigated.

PMID- 9026747
TI  - [The clinical experiences of abortions on demand in a group of 221 adolescents].
AB  - The authors studied about planned abortion performed by girls under 19 years of
      age, during the period 1991-1994. The aim of this study was to evaluate the
      entity of planned abortion also concerning the number of adolescent pregnancy.
      Our study show the percentage of pregnancy was progressively diminished, while
      regarding the planned abortion even if reduced along the time, the percentage
      remain steady in the course of years examined.

PMID- 9026746
TI  - [Ovarian tumefactions: the advantages and limits of echo-guided needle
      aspiration. Our experience].
AB  - One-hundred-seventy-five patients with a probably benign ovarian cyst were
      submitted to transvaginal ultrasound-guided needle aspiration (TVUSGA) for
      diagnostic and therapeutic purpose. Recovery was obtained in 68% of serous cysts
      (130 patients). In 34 endometriotic cysts transvaginal ultrasound guided needle
      aspiration has been an important diagnostic tool and it made possible a better
      therapeutic approach. The cytologic examination of aspirated benign and malignant
      cyst fluid didn't give a satisfactory result every time. In conclusion, the
      transvaginal ultrasound guided needle aspiration has been a good tool in the
      treatment of serous cysts and a diagnostic aid for endometriotic pathology.

PMID- 9026748
TI  - [Uterine fibromas and the hormonal pattern: the therapeutic considerations].
AB  - Uterine fibromyomatosis is a widely recognised and well studied pathology that is
      found in around 30% of over 35-year-old women. It has been extensively
      demonstrated that the etiology of fibromyomas is hormone dependent and to date
      the main pathogenetic role in the development of these benign tumours has largely
      been attributed to estrogens. Uterine fibromyomas have been found to contain a
      higher level of estrogen and progesterone receptors than in normal uterus. This
      suggests an etiopathogenetic role also for progesterone, which is confirmed by
      the higher mitotic index of myomatous tissue cells in luteal phase. Growth
      factors also seem to be involved in the origin of uterine fibromyomatosis:
      concentrations of epidermal growth factor (EGF), insulin like growth factor 1
      (IGF-I) and platelet derived growth factor (PDGF AB) are present in myomatous
      tissues together with their receptors. Recent studies have shown that the
      administration of an anti-progestin compound, like RU 486, causes a reduction in
      fibromyoma size. The role of progesterone in promoting uterine growth opens new
      horizons in the treatment of uterine fibromyomatosis. Treatment with GnRH analogs
      has proved effective in reducing the size of fibromyomas, even if the problem of
      their regrowth once treatment has been suspended remains unsolved. The
      administration of 100 mg of danazol for 6 months after treatment using GnRH
      analogs reduce fibromyoma rebound growth by around 30%.

PMID- 9026749
TI  - [The ovarian renin-angiotensin-aldosterone system].
AB  - The ovarian renin-angiotensin-aldosterone system (OVRAS), although not fully
      known, appears to play an important role in ovarian physiology (steroidogenesis,
      follicular stage, ovulation). The possibility of manipulating ovarian function by
      means of the pharmacological modulation of OVRAS opens new horizons for the
      control of human reproduction.

PMID- 9026750
TI  - [A case of myomectomy for infertility and a following twin pregnancy associated
      with hyperthyroidism].
AB  - The authors describe an infertility case caused by a posterior wall
      subendometrial fibromyoma of the uterus and treated by traditional transcavitary
      myomectomy dwelling upon details of the operative technique. The following
      pregnancy is complicated by twin gestation, hyperthyroidism and preterm delivery.
      Fetuses were born by caesarean section one in good condition, the other affected
      by myelomeningocele with good prognosis. Clinical pictures emerged during
      pregnancy are discussed, in particular the therapy of hyperthyroidism, beta 2
      adrenoceptor stimulants drugs, diagnosis and multifactorial genesis of fetal
      malformation.

PMID- 9026751
TI  - [Pregnancy in women undergoing a kidney transplant. Our experience and a review
      of the literature].
AB  - The chances of pregnancy for uremic women are usually very low, because of
      hormonal balance changes which determine a strong reduction in fertility.
      Epidemiological studies reveal that pregnancy in hemodialyzed women in fertile
      patients 4.6-6 months after a well functioning kidney transplant, one fertile
      transplanted woman over 50 can become pregnant. In the first transplant era,
      pregnancy after kidney transplant was considered "a big hazard", especially
      because of the possible side-effects of immunosuppression drugs on foetus
      development, and the risk of a worsening in the mother's renal function.
      Therefore, women were strongly recommended to avoid pregnancy. More recently,
      several reported papers have shown that pregnancy can be safely carried on also
      by transplanted women, under careful criteria and monitoring. Our experience too,
      even if limited in number (4 patients) reported in this article confirms this
      conviction.

PMID- 9026752
TI  - [Autoimmune thrombocytopenia and pregnancy].
AB  - Immune thrombocytopenic purpura (ITP) is an autoimmune disorder with its highest
      frequency in young women in the reproductive years. An antepartum diagnosis of
      maternal thrombocytopenia has become more common because platelet counts are now
      included with routine complete blood cell counts. Sometimes platelet
      autoantibodies facilitate increased platelet destruction by the
      reticuloendothelial system especially the spleen. These autoantibodies (IgG) can
      cross the placenta and place the fetus at risk for thrombocytopenia and,
      sometimes, serious bleeding problems such as intracranial hemorrhage can occur.
      The treatment is performed by corticosteroids (prednisone) or intravenous immune
      gammaglobulin. Four patients with thrombocytopenia during pregnancy underwent
      medical treatment (prednisone 1 mg/kg/die). The results were successful. In one
      case only we did not have a clinical response after corticosteroid therapy. There
      were no intracranial hemorrhages; however the risk for the patients and fetal or
      neonatal hemorrhage is much lower than thought. Corticosteroid treatment is the
      first choice, but sometimes it can give a clinical negative response.

PMID- 9026753
TI  - [Severe hypertriglyceridemia in pregnancy. A clinical case report].
AB  - Cholesterol (TC) and triglyceride (TG) plasma levels physiologically increase
      during pregnancy. The lipid increment is respectively 23%-53% above pregravidic
      level for TC and two-three fold the pre-pregnancy level for TG. If the TC and TG
      are higher than normal values in pregnancy the patient must be carefully
      monitored. Acute pancreatitis is the main consequence of hyperlipidemia and it
      can occur either during pregnancy, in the third trimester, or in the puerperium.
      Mortality is high both for the mother (21%) and the fetus (20%). The authors
      report a case of 37-year-old pregnant woman at 35 week gestation with
      hypercholesterolemia (TC = 425 mg/dl) and severe hypertriglyceridemia (TG = 3315
      mg/dl). The patient was admitted to the hospital for treatment with an
      appropriate diet and drug lowering lipid levels (gemfibrozil). The baby was
      delivered by cesarean section at week 36. The neonatal weight at birth was 2670 g
      and the Apgar score was 9 at the first minute. After delivery the maternal
      triglyceride levels showed a remarkable reduction. According to a review of the
      literature, severe hypertriglyceridemia in pregnancy should be treated with a
      careful restriction of calories and fat; for preventing acute pancreatitis
      hospitalization for intravenous fluid therapy and plasma exchange must be
      required.

PMID- 9026754
TI  - [A clinical study of the use of a combination of glucomannan with lactulose in
      the constipation of pregnancy].
AB  - RATIONALE: Constipation is a problem frequently encountered during pregnancy as
      is excessive weight gain. Treatments of common use to control constipation are
      endowed with some drawbacks and they are not active in controlling weight
      increase. A preparation of lactulose and glucomannan in previous studies proved
      very effective and well tolerated in patients affected by stypsis and
      evidentiated also activity both in controlling excessive food intake and in
      correcting some metabolic imbalances regarding lipids and urea. MATERIAL AND
      METHODS: 50 pregnant females affected by constipation were treated with sachets
      containing a preparation of glucomannan (1.45 g) and lactulose (4.2 g) in a
      posology of 2 (1-4) sachets a day for 1-3 months. RESULTS: Treatment induced a
      return to normal frequency of weekly number of evacuations (4.9-5.8/week) and a
      parallel control of weight gain (within 20% of initial body weight). The latter
      finding seems to be related to hunger control induced by glucomannan at the
      gastric level which prevents an excessive food intake.

PMID- 9026755
TI  - Hepatitis C virus (HCV) infection and disease in nephrology, dialysis and
      transplantation. Proceedings of the GAMBRO annual symposium. Saint-Etienne,
      France, September 14-15, 1995.

PMID- 9026756
TI  - New drugs.

PMID- 9026757
TI  - [Lipid, apoprotein and fibrinogen levels in the blood of male patients following
      myocardial infarct and the effect of diet on these parameters in ischemic heart
      disease].
AB  - The authors have found significantly higher the levels of two not routinely
      examined risk factors, fibrinogen and lipoprotein (a) in 28 male patients after
      myocardial infarction than the corresponding data of the PROCAM-study and in the
      case of fibrinogen than in 23 healthy blood donors. A positive correlation was
      observed between the LDL-cholesterol and total cholesterol, the LDL-cholesterol
      and the main apoprotein of LDL, the Apo B level, and between the HDL-cholesterol
      and the main apoprotein of HDL, the Apo AI. During a 3 week long treatment in the
      Cardiac Rehabilitation Department the effect of low cholesterol, high unsaturated
      fatty acid content diet on the lipid, apolipoprotein and fibrinogen levels of
      male patients suffering from coronary heart disease with cholesterol level higher
      than 5.2 mmol/l was studied. Significantly decreased the total cholesterol (from
      6.21 +/- 0.96 mmol/l to 5.87 +/- 0.98 mmol/l, -5.5%), the LDL-cholesterol (from
      3.87 +/- 1.02 mmol/l to 3.61 +/- 0.96 mmol/l, -6.7%), the HDL-cholesterol (from
      1.16 +/- 0.39 mmol/l to 1.04 +/- 0.28 mmol/l, -10.3%), the main apoprotein of
      HDL, the Apo AI (from 1.47 +/- 0.23 g/l to 1.33 +/- 0.29 g/l, -9.5%) and the main
      apoprotein of LDL, the Apo B level (from 1.59 +/- 0.43 g/l to 1.46 +/- 0.50 g/l, 
      8.1%). The change of fibrinogen lipoprotein (a) level was not significant.
      According to the earlier observation of the authors and the data of the
      literature, the effect of low cholesterol diet on the change of HDL cholesterol
      was not favourable. The investigation of apolipoprotein levels failed to get
      closer to the understanding of its mechanism.

PMID- 9026758
TI  - [Delta-F508 screening of infants at the Perinatal Intensive Care Center of the
      city if Pecs].
AB  - Cystic fibrosis (CF) is one of the most frequent (1:2500), potentially lethal
      autosomal recessive diseases among Caucasians. Molecular genetic examination has
      become the most valuable method used for diagnosis or population screening. 300
      newborns treated in the Perinatal Intensive Care Unit were examined for the
      mutation delta F508. The results showed that the frequency of affected deltaF508
      homozygotes was 1:100, which is significantly higher than found in the general
      population, but the frequency of carriers (1:33) is similar to the overall value.

PMID- 9026759
TI  - [Aspiration cytology in the diagnosis of gastrointestinal tumors].
AB  - Early experiences with the new endoscopic aspiration cytology method in the
      diagnosis of gastrointestinal malignancies are discussed. It was performed in
      five patients in case of gastric and cardiac cancers and in fifteen ones of colon
      tumours. Results are compared with those of biopsies and brush cytologies. The
      new method is quick, reliable and suggested to be widely used in the
      gastrointestinal endoscopy.

PMID- 9026760
TI  - [Successful twin delivery following reduction of quadruplet pregnancy].
AB  - The authors report first time in the Hungarian literature on multifetal pregnancy
      reduction: a quadruplet pregnancy was reduced to twins on transabdominal way in
      the 16th week of gestation on request of the parents. The quadruplets resulted
      from a forcefully induced ovulation. First weeks of gestation were complicated by
      a severe but effectively treated ovarian hyperstimulation syndrome. Following the
      successful and uncomplicated intervention the course of pregnancy was
      undisturbed, two living healthy babies were delivered in the 35th gestation week.
      Placentae of the liveborn as well as of the stillborn fetuses were pathologically
      examined. On occasion of the case report theoretical and practical questions of
      multifetal pregnancy reduction are discussed in details from indications through
      technical implementation to a review of legal, ethical and also psychological
      relations of that intervention. A standpoint for the national practice is also
      framed by the authors.

PMID- 9026761
TI  - [Neurofibromatosis with abdominal and severe central nervous system
      complications].
AB  - A young male patient suffered in cutaneous neurofibromatosis was followed during
      four years. He developed tissue proliferations of various histological structures
      manifested in the skin, central nervous system and different splanchnic organs.
      The classification criteria of neurofibromatosis as well as the diagnostic and
      therapeutic recommendations are discussed.

PMID- 9026762
TI  - [100th anniversary of the Hungarian Association of Gynecologists].

PMID- 9026763
TI  - [Globalization of psychiatric research].

PMID- 9026764
TI  - [Rh alloimmunization].

PMID- 9026765
TI  - [Is it unusual to find auditory ossicles among medieval fossils?].

PMID- 9026766
TI  - [Treatment of achalasia of the cardia using thoracoscopic esophago-myotomy].
AB  - We performed left thoracoscopic esophagomyotomy in four patients suffering from
      achalasia cardiac. In one patients the esophageal mucosa was opened during the
      myotomy. This was sutured through thoracoscopy and the per os feeding of the
      patient started on the 8th postoperative day, while in the other three patients
      this was done on the 2nd postoperative day. The mean emission of the patients was
      on the 6th postoperative day. Comparison of the status before and 6 weeks
      following the operation was done on the basis of results of different
      examinations i. e. x-ray, esophago-gastroscopy, manometry, pH-metry, isotope
      test. The favourable results of the operations were declared as all examinations
      revealed marked improvement and all patients have better swallow function and 6-9
      kg increase in body weight.

PMID- 9026767
TI  - [Study of low density lipoprotein (LDL) receptor mutations, using restriction
      endonucleases, in familial hypercholesterolemia].
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant metabolic disorder
      caused by different mutations in the low density lipoprotein receptor (LDLR)
      gene. We analyzed 13 families (23 patients) with FH and 36 subjects with
      normocholesterolemia by restriction fragment polymorphism (RFLP) using enzymes
      Xbal, BgIII and PvuII. At the 3' end of LDLR an extra 4.4 kb band has been found
      by Xbal digestion in one patient and it has been proved to be a "de novo" form of
      mutation. In the 5' end of LDLR gene a combined mutation has been identified in
      two FH families. The Xbal RFLP has yielded an extra band of 24.5 kb and an
      another extra band of 17.5 kb has been found by BgIII digestion. It has been
      suggested that the simultaneous occurrence of 3.3 kb extended deletion (intron 3)
      and 4.8 kb extended insertion (intron 1) is present. In our study the frequency
      of P2 allele (PvuII RFLP) in FH patients did not differ from normocholesterolemic
      controls.

PMID- 9026768
TI  - [Congenital broncho-esophageal fistula manifesting in adult age].
AB  - Congenital bronchoesophageal fistula manifesting in adulthood is an infrequent
      disorder. Presenting a successfully treated case, the authors review the
      clinicopathological features of the disease regarding the data of literature. The
      long-standing, non-specific respiratory symptoms recurring in the same pulmonary
      location call the attention to the fistula, which should be verified by
      esophagography and endoscopy. The adequate treatment consisting of fistulectomy
      and resection of the destroyed lung parenchyma lead to prompt recovery.

PMID- 9026769
TI  - [Epidemiology and clinical significance of the newly discovered GB,G hepatitis
      viruses].
AB  - A number of hepatitis viruses have been newly identified belonging to the family
      hepatitis A-E, by their genome structure. The authors summarize and briefly
      demonstrate the most important molecular and epidemiological characteristics of
      te hepatitis GB and G viruses, and they discuss their clinical significance. They
      discuss the similarities and differences recording the three GB (GB-A, GB-B, GB
      C) viruses, and also stress the high rate of similarity between the GB-C and G
      viruses. All the three GB viruses and G virus have RNA-genome, all of them are
      transferable with blood and blood preparates, they have been found both in acute
      and chronic hepatitis. They occur with higher rate in high risk population where
      the frequency of hepatitis B and C also increased.

PMID- 9026771
TI  - [Interferon therapy in cryoglobulinemic membranoproliferative glomerulonephritis
      associated with hepatitis C].

PMID- 9026770
TI  - [Amiodarone-induced pulmonary fibrosis].

PMID- 9026772
TI  - [Clinical diagnosis of childhood insulin dependent diabetes mellitus. Hungarian
      Epidemiological Group for Childhood Diabetes].
AB  - The aim of this study was to describe the clinical presentation and severity of
      the disease at onset in childhood during 1994. Based on the prospective national
      incidence registry, data were collected (using a modified version of the EURODIAB
      ACE questionnaire) from all diabetic children diagnosed during a full calendar
      year (1994). The ascertainment was 91%. Polyuria, polydipsia and weight loss were
      the most frequent clinical symptoms, but fatigue, abdominal pain and personality
      changes were also often reported. Almost one quarter of the children presented
      with diabetic ketoacidosis. There was no correlation between age, duration of
      symptoms, blood glucose levels and the severity of disease. The unacceptably high
      incidence of presentation ketoacidosis called for an urgent improvement of the
      diagnostic acumen of the physicians dealing with children.

PMID- 9026773
TI  - Responses of Purkinje cells in the cerebellar anterior vermis to off-vertical
      axis rotation.
AB  - Responses of 67 Purkinje cells (P-cells) and 44 unidentified neurons (U-cells)
      located in the cerebellar anterior vermis were recorded in decerebrate cats
      during off-vertical axis rotation (OVAR). This stimulus consisted of a slow
      constant velocity (9.4%/s) rotation in the clockwise (CW) and counterclockwise
      (CCW) directions around an axis inclined by 5 degrees with respect to the
      vertical. OVAR imposes on the animal head a 5 degrees tilt, whose direction
      changes continuously over the horizontal plane, thus eliciting a selective
      stimulation of macular receptors. A total of 27/67 P-cells (40%) and 24/44 U
      cells (55%) responded to both CW and CCW rotations. For these bidirectional
      units, the direction of maximum sensitivity to tilt (Smax) could be identified.
      Smax directions were distributed over the whole horizontal plane of stimulation.
      Among bidirectional neurons, 48% of the P-cells and 33% of the U-cells displayed
      an equal amplitude of modulation during CW and CCW rotations, indicating a cosine
      tuned behaviour. In these instances, the temporal phase of the unit response to a
      given direction of tilt remained constant, while the sensitivity was maximal
      along the Smax direction and declined with the cosine of the angle between Smax
      and the tilt direction. The remaining bidirectional units displayed unequal
      amplitudes of modulation during CW and CCW rotations. For these neurons, a
      nonzero sensitivity along the null direction was expected and the response phase
      varied as a function of stimulus direction. Finally, 31% and 23% of P-cells and U
      cells, respectively, responded during OVAR in one direction only (unidirectional
      units). This behaviour predicts equal sensitivities along any tilt direction in
      the horizontal plane and a response phase that changes linearly with the stimulus
      direction. The posibility that the tested neurons formed a population which coded
      the direction of head tilt in space was also investigated. The data from the
      whole population of cells were analysed using a modified version of vectorial
      analysis. This model assumes that for a particular tilt each cell makes vectorial
      contributions; the vectorial sum of these contributions represent the outcome of
      the population code and points in the direction of head tilt in space. Thus, a
      dynamic head tilt along four representative directions was simulated. For each of
      the four directions, 12 population vectors were calculated at regular time
      intervals so as to cover an entire cycle of head tilt. The results indicate that
      for each selected time in the cycle the direction of the population vector
      closely corresponded to that of the head tilt, while its amplitude was related to
      the amount of head tilt. These data were particularly obtained for the P-cells.
      In view of their efferent connections, the cerebellar anterior vermis may provide
      a framework for the spatial organization of vestibulospinal reflexes induced by
      stimulation of otolith receptors.

PMID- 9026774
TI  - Inhibition of tumor necrosis factor in the brain suppresses rabbit sleep.
AB  - Tumor necrosis factor (TNF) is a cytokine that possesses many biological
      activities, including enhancement of non-rapid-eye-movement sleep (NREMS). The
      role of endogenous TNF in the regulation of spontaneous sleep is unknown. If TNF
      is involved in sleep regulation, then reduction of endogenous TNF should suppress
      spontaneous sleep. A soluble TNF-binding protein I (TNF-BP I) and a synthetic
      fragment of TNF-BP I, TNF-R-(159-178), that contains the biologically active
      region of TNF-BP I, were used. These substances bind TNF and possess TNF
      inhibitory activity; their effects on rabbit sleep after intracerebroventricular
      injection were determined across a 6-h recording period. Two doses of TNF-BP I
      (0.05 micrograms and 0.5 micrograms) were administered; the higher dose of TNF-BP
      I significantly decreased NREMS. Four doses of TNF-R-(159-178) (0.25 micrograms,
      2.5 micrograms, 25 micrograms and 50 micrograms) were used. The 25 micrograms and
      50 micrograms doses significantly suppressed NREMS. The highest dose (50
      micrograms) also decreased REM sleep. These results are consistent with the
      hypothesis that endogenous brain TNF is involved in the regulation of normal
      sleep.

PMID- 9026775
TI  - Muscarinic regulation of phospholipase D and its role in arachidonic acid release
      in rat submandibular acinar cells.
AB  - The characteristics of muscarinic cholinergic-induced phospholipase D (PLD)
      activation, and the involvement of the enzyme in the release of arachidonic acid
      were examined in rat submandibular acinar cells. Carbachol produced a dose
      related activation of PLD to around fivefold control values at 100 microM agonist
      concentration. This was associated with the appearance of free choline,
      phosphatidic acid and arachidonic acid, indicating that the PLD substrate was
      phosphatidylcholine. The response to carbachol was inhibited by 60% by U73122, a
      blocker of a phospholipase C (PLC) specific to phosphatidylinositol 4,5
      bisphosphate [PtdIns(4,5)P2], suggesting that the cleavage of phosphatidylcholine
      by PLD was, at least in part, secondary to agonist-coupled hydrolysis of
      PtdIns(4,5)P2 by PLC. Consistent with this, PLD was also activated to levels
      comparable to those induced by carbachol, by the phorbol ester, 12-O
      tetradecanoylphorbol-13-acetate (TPA), and the Ca2+ mobilizer, thapsigargin, two
      agents that respectively mimic the activation of protein kinase C (PKC) by
      diacylglycerol and the elevation of cytosolic Ca2+ by inositol 1,4,5-triphosphate
      [Ins(1,4,5)P3] in the phosphoinositide effect. The cell-permeant Ca2+ chelator
      1,2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl
      ester (BAPTA/AM) abolished the thapsigargin-induced activation of PLD and
      inhibited the responses of PLD to carbachol and TPA by 60%. The PKC inhibitor, Ro
      31-8220, also inhibited the activation of PLD by carbacol and TPA to a level of
      approximately double control values, but had no effect on the thapsigargin
      induced elevation of PLD. A role for both the PKC-associated and Ca(2+)
      mobilizing arms of the PtdIns(4,5)P2-PLC pathway in PLD regulation is thus
      suggested. Pretreatment of cells with the phosphatidate phosphohydrolase blocker,
      propranolol, significantly enhanced the carbachol-induced elevation of
      phosphatidic acid, but decreased agonist-stimulated production of diacylglycerol
      and arachidonic acid, indicating that phosphatidlycholine was the likely source
      of arachidonic acid. We therefore propose that, in submandibular mucous acinar
      cells, muscarinic activation of the PtdIns(4,5)P2-PLC pathway regulates
      phosphatidylcholine-specific PLD through both the PKC- and Ca(2+)-mobilizing arms
      of the phosphoinositide response, and that diacylglycerol, derived from
      phosphatidylcholine via phosphatidic acid, is a source of free arachidonic acid.

PMID- 9026776
TI  - Rhythmic Cl- current and physiological roles of the intestinal c-kit-positive
      cells.
AB  - Chronic injection of an anti-c-KIT receptor tyrosine kinase monoclonal antibody
      (ACK2) results in the disruption of the normal motility patterns of young BALB/c
      mice intestine. This effect is accompanied by a drastic decrease in the number of
      intestinal c-kit-expressing (c-kit+) cells when studied immunohistochemically
      with the fluorescence-labelled antibody. In order to clarify the mechanism
      underlying the ACK2 action and the physiological roles of intestinal c-kit+
      cells, we studied the excitability of intestinal c-kit+ cells in primary culture
      by use of the nystatin perforated-patch-clamp technique. Under voltage-clamp at 
      40 mV, the majority of c-kit+ cells tested (59/70) elicited rhythmic current
      waves with an amplitude and frequency of 263 +/- 24 pA and 2.30 +/- 0.25
      cycles/min (mean +/- SEM), respectively. Intracellular perfusion of the c-kit+
      cells with ethylenebis (okonitrilo) tetraacetate (EGTA) as well as a nominally
      Ca(2+)-free external solution or low holding voltage (< -60 mV) prevented the
      rhythmic current. The reversal potential of the rhythmic current was close to the
      equilibrium potential for Cl-(ECl). Moreover the rhythmic current was depressed
      by a Cl- channel blocker, 4-acetoamido-4-isothiocyanat-ostilbene-2,2'-disulphoni
      c acid (SITS). The smooth muscle cells freshly dissociated from the same
      intestinal specimen revealed a Ca(2+)-activated K+ current, as has been described
      in a variety of smooth muscle cells. Cultured smooth muscle cells from the ileum
      preparation lacked neither the Ca(2+)-activated K+ nor rhythmic Cl- currents.
      Smooth muscle cells freshly dissociated from the same ileum preparation and those
      in culture showed no immunoreactivity with the labelled ACK2, which was
      consistent with our previous in situ study. Results provided direct evidence that
      the intestinal c-kit+ cells, but not the smooth muscle cells, possess a rhythmic
      Cl- current oscillation, suggesting their participation in pacemaker activity for
      the peristaltic gut movement.

PMID- 9026777
TI  - Tyrosine protein kinase inhibitors prevent activation of cardiac swelling-induced
      chloride current.
AB  - The effect of tyrosine protein kinase inhibitors on the swelling-induced chloride
      current (ICl-swelling) of dog atrial myocytes was studied using the whole-cell
      patch-clamp recording technique. Currents were measured during hyperpolarizing
      voltage ramps with potassium currents blocked by cesium. Osmolarity was varied
      using mannitol. Exposure to hypotonic solution (approximately 249 mosmol/kg)
      activated ICl-swelling. Hypertonic solution (approximately 363 mosmol/kg) was
      used to shrink swollen cells and turn off ICl-swelling. In studies on the acute
      effect of tyrosine protein kinase inhibitors each cell was swollen three separate
      times. Control, treatment, and washout ICl-swelling were compared. Genistein (50
      80 microM) prevented reactivation of ICl-swelling without affecting cell size.
      The effect of genistein partially subsided upon washout. The effect of genistein
      on ICl-swelling was not mimicked by 80 microM daidzein, a related compound that
      does not inhibit tyrosine protein kinases. When intracellular adenosine 5'-O-(3
      thiotriphosphate (ATP[gamma S]) was used, genistein did not prevent the
      reactivation of ICl-swelling. Intracellular ATP[gamma S] did not result in a
      persistent activation of ICl-swelling when cell size was returned to control.
      Acute exposure to 1 microM herbimycin A or 100 microM tyrphostin 51 did not
      prohibit the activation of ICl-swelling. A 24-h exposure to 1 microM herbimycin A
      did inhibit ICl-swelling. The results provide important clues regarding the
      activation mechanism for ICl-swelling and suggest that a tyrosine protein
      phosphorylation may be necessary, but not sufficient, for activation of ICl
      swelling.

PMID- 9026778
TI  - Modulation of Na+ channel inactivation by the beta 1 subunit: a deletion
      analysis.
AB  - Na+ currents recorded from Xenopus oocytes expressing the Na+ channel alpha
      subunit alone inactivate with two exponential components. The slow component
      predominates in monomeric channels, while co-expression with the beta 1 subunit
      favors the fast component. Macropatch recordings show that the relative rates of
      these components are much greater than previously estimated from two-electrode
      measurements (approximately 30-fold vs approximately 5-fold). A re-assessment of
      steady-state inactivation, h infinity (V), shows that there is no depolarized
      shift of the slow component, provided a sufficiently long prepulse duration and
      repetition interval are used to achieve steady-state entry and recovery from
      inactivation, respectively. Deletion mutagenesis of the beta 1 subunit was used
      to define which regions of the subunit are required to modulate inactivation
      kinetics. The carboxy tail, comprising the entire predicted intracellular domain,
      can be deleted without a loss of activity; whereas small deletions in the
      extracellular amino domain or the signal peptide totally disrupt function.

PMID- 9026779
TI  - Swelling-induced catecholamine secretion recorded from single chromaffin cells.
AB  - We have studied osmotically induced catecholamine secretion from bovine adrenal
      chromaffin cells by combining patch-clamp measurements, electrochemical detection
      of secretion, and Fura-2 measurements of intracellular free calcium concentration
      ([Ca2+]i). We find that osmotically induced catecholamine release is exocytotic
      and calcium dependent. Furthermore, we demonstrate that cell swelling is coupled
      to such secretion via a volume-activated current, carrying predominantly
      chloride, which causes a plateau depolarization of the cell membrane potential
      and thus promotes voltage-activated calcium influx. Therefore, cell volume
      changes may modulate the secretory activity.

PMID- 9026780
TI  - The response of adult and developing rat plantaris muscle to overload.
AB  - The effect of overload on the rat plantaris muscle was studied in animals of
      different ages. Overload was induced by removal of gastrocnemius and soleus
      muscles. As expected, when the operation was carried out in adults, the plantaris
      muscle became heavier and stronger. These changes occured within 30 days after
      the operation. In animals in which the operation was carried out 1-12 days after
      birth and the muscle examined 6-20 weeks later, different results were obtained.
      In the group operated at 1-9 days of age, the muscles developed a lower maximal
      twitch and tetanic tension than the contralateral plantaris muscle. There was no
      difference in the time to peak or muscle weight between the overloaded and the
      contralateral muscles. Similar changes were observed in animals where the
      overload was induced at 11 or 12 days of age except for the weight which was
      significantly higher than that of the control plantaris muscles. The number of
      slow fibers increased in animals where overload was induced 11-12 days
      postnatally or in adults, but not when muscles were overloaded at 9 days of age.
      The possible reasons for the different response of adult and neonatal muscles to
      overload are discussed.

PMID- 9026781
TI  - Effects of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin I2 (PGI2) on
      nerve-mediated secretion in guinea-pig colon.
AB  - We have applied conventional flux-chamber and intracellular recording methods to
      investigate the effects of the prostaglandins PGF2 alpha and PGI2 upon epithelial
      ion transport and on the electrical behaviour of submucosal neurones in guinea
      pig colon. In flux-chamber experiments on segments of colon, both prostaglandins
      evoked a dose-dependent increase in short-circuit current that was reduced in
      chloride-depleted Krebs solution and by serosal addition of tetrodotoxin or
      atropine, but was unaffected by hexamethonium. These results indicate activation
      of chloride secretion via submucosal neurones. The response to PGF2 alpha was
      decreased by piroxicam. Application of PGF2 alpha or PGI2 to submucosal neurones
      evoked depolarization of the membrane potential associated with an enhanced spike
      discharge. The depolarizing response was tetrodotoxin insensitive, indicating a
      direct effect of the prostaglandins on the impaled neurones. Membrane
      depolarization was frequently associated with the occurrence of fast excitatory
      postsynaptic potentials, suggesting in addition that part of the excitatory
      effect is mediated by the activation of neural circuits that drive the impaled
      neurone synaptically. The results of this study indicate that the secretory
      effects of prostaglandins are mediated in part by submucosal neurones and further
      suggest that the colonic submucosal plexus may function as an amplifier to
      enhance the epithelial response to inflammatory mediators.

PMID- 9026783
TI  - Measures of "fastness": force profiles of twitches and partly fused contractions
      in rat medial gastrocnemius and tibialis anterior muscle units.
AB  - Recordings of isometric force were obtained for twitches and (sub)maximal tetani
      of gastrocnemius medialis (MG) and tibialis anterior (TA) muscle units in female
      Wistar rats. We assessed the relationships between unit properties that have all
      been associated with "speed": (1) the relative degree of peak force attained
      during repetitive activation at 40 Hz (P40/Pmax), (2) the relative degree of
      final twitch fusion during the same test burst (Fus-end), and (3) various
      measures of the time-course of single twitches, including twitch time-to-peak and
      a parameter referred to as "initial fusion ratio" (Fus-in; relative decline from
      peak force at 25 ms from twitch onset). The various measures of twitch time
      course were significantly correlated to each other with correlation coefficients
      varying over a fairly wide range (0.35-0.64 for MG; 0.50-0.80 for TA). Twitch
      time-course was also significantly correlated with Fus-end during the 40-Hz
      repetitive activation; the highest correlation coefficient (0.69 for MG, 0.80 for
      TA) was obtained for Fus-in, which was also numerically similar to Fus-end. Thus,
      the degree of fusion indeed seemed to be largely dependent upon aspects of twitch
      time-course. However, the relative degree of force mobilization obtained in the
      same contractions elicited by stimulation at 40 Hz was not consistently better
      correlated with Fus-end than with measures of single twitch time-course.
      Furthermore, in fast-twitch units having the same twitch time-to-peak, the force
      mobilization elicited by stimulation at 40 Hz (P40/Pmax) was the same for MG and
      TA, while the degree of fusion was significantly smaller for TA than for MG
      units. The results demonstrate the complexity of the concept of isometric "speed"
      and underline the need for using several speed indicators in parallel in studies
      concerning the differentiation of muscle (unit) properties.

PMID- 9026782
TI  - Single-channel analysis of two types of Na+ currents in rat dorsal root ganglia.
AB  - The properties of voltage-gated Na+ channels were studied in neurones isolated
      from rat dorsal root ganglia using the outside-out configuration of the patch
      clamp technique. Two types of single-channel currents were identified from the
      difference in unit amplitudes. Neither type was evoked in the medium in which
      extracellular Na+ ions were replaced by an equimolar amount of
      tetramethylammonium ions. The two types of single-channel currents differed in
      their sensitivity to tetrodotoxin (TTX). The smaller channel current was
      insensitive to 1 microM TTX (referred to as TTX-I), while the larger channel
      current was blocked by 1 nM TTX (TTX-S). The unit amplitudes measured during a
      step depolarization to -30 mV (1.4 mM internal and 250 mM external Na+
      concentrations) were 1.16 pA for TTX-S and 0.57 pA for TTX-I, respectively. The
      slope conductance measured at -30 mV was 16.3 pS for TTX-S and 8.5 pS for TTX-I.
      TTX-S could be activated by step depolarizations positive to -60 mV, while TTX-I
      could be activated at potentials positive to -40 mV. When the test pulse was
      preceded by a depolarizing prepulse, the prepulse positive to -50 mV
      preferentially inactivated TTX-S with a minimal effect on TTX-I. Activation and
      inactivation time courses of the averaged ensemble currents computed from TTX-S
      showed remarkable resemblances to the time courses of the macroscopic TTX
      sensitive Na+ current. Similarly, the ensemble currents of TTX-I mimicked the
      macroscopic TTX-insensitive Na+ current. It was concluded that the two types of
      Na+ channels in rat dorsal root ganglia differ not only in their sensitivity to
      TTX, but also in their single-channel conductances.

PMID- 9026784
TI  - Effects of clenbuterol and ICI118551, a selective beta 2-antagonist, on the
      growth of skeletal muscle of suckling rats.
AB  - The beta 2-adrenergic agonist, clenbuterol, was administered to lactating rats (4
      mg/kg diet) from post-partum day 1 to day 19, or directly injected into neonate
      rats (0.1 and 1.0 mg/kg body weight) from post-partum day 3 until day 15. Changes
      in body weight and the skeletal muscles soleus (SOL) and extensor digitorum
      longus (EDL) were studied in both dams and suckling offspring. Drug treatment
      consistently increased body weight in dams whilst significantly reducing the
      growth of their suckling pups. In dams treated with clenbuterol (4 mg/kg of diet)
      muscle weights and protein contents were significantly increased. Total protein
      content increased by 16% in SOL and 47% in EDL after 19 days of treatment. In
      contrast, in their suckling pups, there was a 22% and 26% reduction in protein
      content of SOL and EDL respectively. Administration of the beta 2-antagonist
      ICI118551 to these pups failed to prevent these reductions in body and muscle
      weights. Hence, if clenbuterol did reach the pups via the milk from treated
      mothers it did not act via conventional beta 2-receptors. Injection of pups with
      clenbuterol (1.0 mg/kg every 12 h) from litters suckling from untreated dams also
      resulted in significant reductions in muscle weights and protein contents.
      Protein content was reduced by 10% in SOL and 13% in EDL after 12 days of
      treatment. No alteration in fibre type proportion in SOL or EDL resulted from
      this treatment. Further work is required to determine whether the growth
      suppression in the two situations occurs via the same mechanism.

PMID- 9026786
TI  - Ca2+ entry and vasoconstriction during osmotic swelling of vascular smooth muscle
      cells.
AB  - Exposure of aortic strips from guinea-pigs to hypotonic extracellular fluid is
      followed by marked vasoconstriction, which is inhibited by D-600 (3 microM), a
      blocker of voltage-sensitive Ca2+ channels. Conventional electrophysiology, patch
      clamp studies, pH determination with 2',7' bis(2-carboxyethyl)-5,6
      carboxyfluorescein (BCECF) and Ca2+ measurements with Fura-2 have been performed
      on smooth muscle cells cultured either from rat or human aorta to further
      elucidate the underlying mechanisms. Exposure of the cells to a 25% hypotonic
      extracellular fluid leads to a rapid and fully reversible depolarization,
      paralleled by an increase of the selectivity and conductance of the cell membrane
      to Cl-, an acidification of the cytoplasm and an increase of intracellular Ca2+
      concentration ([Ca2+]i). The latter is inhibited by the Ca2+ channel blocker D
      600 (1-3 microM). It is concluded that osmotic cell swelling leads to the
      activation of an anion channel. The subsequent depolarization of the cell
      membrane activates voltage-sensitive Ca2+ channels which increases [Ca2+]i, thus
      stimulating the contraction of vascular smooth muscle cells.

PMID- 9026785
TI  - Developmental variation of the permeability to Ca2+ of AMPA receptors in presumed
      hilar glial precursor cells.
AB  - Glial cells in the hilus of the dentate gyrus of the rat were investigated using
      the patch-clamp technique in acute slices of the hippocampal formation. According
      to their voltage-gated current patterns, two classes of glial cells--putative
      astrocytes and presumed glial precursor cells--were apparent. The glutamate
      receptor agonists kainate, glutamate, and alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionate (AMPA) evoked inward currents at a holding potential of -70
      mV in astrocytes and presumed glial precursor cells. Inward currents could also
      be induced in nucleated patches, indicating a direct action on glial receptors.
      In presumed hilar glial precursor cells, 6,7-dinitroquinoxaline-2,3-dione (DNQX;
      10 microM) blocked the kainate-induced current, while it was partially inhibited
      by Zn2+ (2 mM) and Evans Blue (10 microM). Cyclothiazide (100 microM), in
      contrast, potentiated this current, indicating the presence of AMPA receptors. In
      90% of the presumed glial precursor cells the excitatory amino-acid-evoked
      current voltage (I/V) relations were linear or outwardly rectifying and reversed
      close to 0 mV, which is characteristic for non-specific cation channels. To
      determine the permeability to Ca2+, I/V relations were determined in a Na(+)-free
      solution containing 40 mM Ca2+ and showed reversal potentials of a wide variation
      ranging from -63 mV to +1 mV with corresponding PCa/PCs permeability ratios of
      between 0.09 and 2.10. Statistical analysis revealed that the permeability to
      Ca2+ significantly decreased with an advance in age (r = -0.596; n = 21; P <
      0.01). These data suggest that the Ca2+ influx mediated by the activation of AMPA
      receptors expressed in presumed hilar glial precursor cells is dependent on the
      developmental stage.

PMID- 9026787
TI  - Rapid activation of glycogen synthase and protein phosphatase in human skeletal
      muscle after isometric contraction requires an intact circulation.
AB  - The effects of isometric contraction (66% of maximal force) and recovery on
      glycogen synthase fractional activity (GSF) in human skeletal muscle have been
      studied. Biopsies were taken from the quadriceps femoris muscle at rest, at
      fatigue and 5 min postexercise on two occasions: after one of the contractions,
      the circulation to the thigh was occluded during the 5 min recovery (OCC), and
      after the other contraction, the circulation was intact (control, CON). During
      CON, GSF decreased from (mean +/- SE) 0.34 +/- 0.05 at rest to 0.24 +/- 0.02 at
      fatigue and then increased to 0.74 +/- 0.04 at 5 min postexercise; corresponding
      values for OCC were 0.37 +/- 0.04, 0.25 +/- 0.04 and 0.48 +/- 0.05 (P < 0.001 vs.
      CON for 5 min postexercise only). Compared with the value at fatigue, protein
      phosphatase activity (PP) increased by 79 +/- 16% during CON recovery (P < 0.01),
      whereas no change was observed during OCC recovery. Uridine diphosphate glucose
      increased by approximately 2.5-fold at fatigue, remained elevated during OCC
      recovery, but reverted to the preexercise level during CON recovery (P < 0.001
      vs. OCC recovery). Glucose 6-P increased approximately 5-fold at fatigue and was
      higher at 5 min postexercise in OCC vs. CON recovery (8.6 +/- 1.5 vs. 4.1 +/- 0.9
      mmol/kg dry wt; P < 0.01). It is concluded that the rapid increase in GSF after
      intense exercise with an intact circulation may be at least partly attributed to
      an increase in the specific activity of PP. The increase in GSF during recovery
      in OCC may be at least partly attributed to the high glucose 6-P content in vivo,
      which enhances the substrate suitability of GS for PP. Thus, separate mechanisms
      exist for the activation of PP and GS during recovery from intense short term
      exercise.

PMID- 9026788
TI  - Thyroid hormone stimulation of Na/Pi-cotransport in opossum kidney cells.
AB  - Thyroid hormone (T3), a known stimulator of renal proximal tubular brush border
      membrane Na-dependent phosphate (Pi) uptake (Na/Pi-cotransport), stimulated Na
      dependent Pi transport in opossum kidney (OK) cells. Na/Pi-cotransport was
      stimulated in a time- and dose-dependent manner with maximal effects (57%) at 24
      h and 10(-10) M T3. This stimulation was related to an increase in the apparent
      capacity (Vmax) of Na/Pi-cotransport. Treatment with T3 had no effect on Na
      independent transport of Pi or of L-arginine. The stimulation of Na/Pi
      cotransport was paralleled by an increase in the messenger ribonucleic acid
      (mRNA) encoding the OK cell apical Na/Pi-cotransporter (termed NaPi-4); the mRNA
      levels related to the activity of Na-independent L-arginine transport (rBAT) were
      unaffected by T3. Actinomycin D (10(-7) M) completely prevented the stimulatory
      effect of T3 on OK cell Na/Pi-cotransport and on NaPi-4 mRNA content. In
      conclusion, T3 stimulates apical Na/Pi-cotransport in OK cells most likely by
      enhancing its transcription.

PMID- 9026789
TI  - Voltage-dependent Na+ and Ca2+ currents in human pancreatic islet beta-cells:
      evidence for roles in the generation of action potentials and insulin secretion.
AB  - We describe three voltage-dependent inward currents in human pancreatic beta
      cells. First, a rapidly inactivating Na+ current, blocked by tetrodotoxin (TTX)
      is seen upon brief depolarization to or beyond -40 mV. Second, a transient, low
      voltage-activated (LVA), amiloride-blockable Ca2+ current is seen upon
      depolarization to or beyond -55 mV; it inactivates within less than 1s of
      sustained depolarization to -40 mV. Third, a more sustained, high-voltage
      activated (HVA) Ca2+ current, which shows variable sensitivity to
      dihydropyridines is seen upon depolarization to or beyond -40 mV, and thereafter
      slowly inactivates over a time course of many seconds. Our pharmacological
      evidence suggests that all three currents contribute to action potential
      initiation and upstroke when the background membrane potential (Vm) is equal or
      negative to -45 to -40 mV, a situation often induced by glucose concentrations (5
      6 mM) in the range of those seen post-prandially. Consistent with this, TTX
      drastically reduces both transient and sustained insulin secretion in the
      presence of 5-6 mM glucose, but has little effect in 10 mM glucose, at which
      concentration cells rapidly depolarize to approximately -35 mV, a Vm sufficient
      to rapidly inactivate Na+ and LVA Ca2+ currents.

PMID- 9026790
TI  - Effects of tyramine and calcium on the kinetics of secretion in intact and
      electroporated chromaffin cells superfused at high speed.
AB  - Fast superfusion of electroporated bovine adrenal chromaffin cells with a K+
      glutamate-based solution containing 50 nM free Ca2+ and 2 mM adenosine 5'
      triphosphate, dipotassium salt (K2ATP), produced a steady-state low catecholamine
      secretion, measured on-line with an electrochemical detector (about 20 nA). Rapid
      switching to electroporation solutions containing increasing Ca2+ concentrations
      ([Ca2+]) produced a rapid increase in the rate and peak secretion, followed by a
      decline. At intermediate [Ca2+] (3-100 microM), a fast peak and a slow secretory
      plateau were distinguished. The fast secretory peak identifies a readily
      releasable catecholamine pool consisting of about 200-400 vesicles per cell.
      Pretreatment of cells with tyramine (10 microM for 4 min before electroporation)
      supressed the initial fast secretory peak, leaving intact the slower phase of
      secretion. With [Ca2+] in the range of 0.1-3 microM, the activation rate of
      secretion increased from 2.3 to 35.3 nA.s-1, reached a plateau between 3-30
      microM and rose again from 100 to 1000 microM [Ca2+] to a maximum of 91.9 nA.s-1.
      In contrast, total secretion first increased (0.1-1 microM Ca2+), then plateaud
      (1-100 microM Ca2+) and subsequently decreased (100-1000 microM Ca2+). At 30 and
      1000 microM extracellular [Ca2+] or [Ca2+]o, the activation rates of secretion
      from intact cells depolarised with 70 mM K+ were close to those obtained in
      electroporated cells. However, secretion peaks were much lower in intact (93 nA
      at 30 microM Ca2+) than in electroporated cells (385 nA). On the other hand,
      inactivation of secretion was much faster in intact than in electroporated cells;
      as a consequence, total secretion in a 5-min period was considerably smaller in
      intact (10.6 microA.s at 1000 microM Ca2+) than in electroporated cells (42.4
      microA.s at 1 microM Ca2+). Separation of the time-courses of changes in
      intracellular [Ca2+] or [Ca2+]i and secretion in intact chromaffin cells
      depolarised with 70 mM K+ was demonstrated at different [Ca2+]o. The increase in
      the rate of catecholamine release was substantially higher than the increase of
      the average [Ca2+]i. In contrast, the decline of secretion was faster than the
      decline of the peak [Ca2+]i. The results are compatible with the idea that the
      peak and the amount of catecholamine released from depolarised intact cells is
      determined essentially by plasmalemmal factors, rather than by vesicle supply
      from reserve pools. These plasmalemmal factors limit the supply of Ca2+ by the
      rates of opening and closing of voltage-dependent Ca2+ channels of the L- and Q
      subtypes, which control the local [Ca2+]i near to exocytotic sites.

PMID- 9026791
TI  - Voltage-dependent inactivation of volume-regulated Cl- current in human T84
      colonic and B-cell myeloma cell lines.
AB  - The voltage-dependent inactivation of a volume-regulated Cl- current (VRChlC) in
      an epithelial (T84), and a B cell myeloma (RPMI-8226) cell lines were compared.
      Both cell types exhibited similar time and voltage-dependent current inactivation
      when recorded using standard whole cell patch technique, with a NaCl external
      solution that was approximately 90 mOsm hypotonic to the Cs-Glutamate internal
      solution. The time course of voltage-dependent current inactivation was fit by
      the sum of a slow, dominant voltage-dependent and a faster voltage-independent
      components. Recovery from inactivation was approximated by a single exponential
      process and was dependent on the recovery voltage. The major difference was that
      the voltage-dependent current inactivation in myeloma cells was shifted to a
      approximately 30mV more depolarized value than that in T84 cells although the
      effective charge movement of inactivation was similar. These results indicate
      that the macroscopic volume-regulated Cl- current in these two cell lines is
      functionally similar.

PMID- 9026793
TI  - [The clinico-physiological manifestations and the pathophysiological mechanisms
      of respiratory failure in tuberculosis and nonspecific lung diseases].
AB  - One hundred and forty-seven patients with tuberculosis and nonspecific lung
      diseases underwent comprehensive clinical and physiological studies at rest and
      during exercises of 0.5 and 1.0 W per kg body weight of the examinee. Respiratory
      failure was found in more than half of them, which was due to pulmonary
      insufficiency in the vast majority of cases and due to cardiopulmonary
      insufficiency in much fewer cases. In the two respiratory failures, impaired
      mechanics of respiration and distributive function of the lung play the leading
      role in the development of respiratory function. The contribution of the impaired
      diffusion capacity of the lung as a cause of arterial hypoxemia increases with
      the severity of diffusive disorders and during exercises.

PMID- 9026792
TI  - Horseradish peroxidase transport across rat alveolar epithelial cell monolayers.
AB  - PURPOSE: To evaluate the transport characteristics of horseradish peroxidase
      (HRP, a nonspecific fluid-phase endocytosis marker) across an in vitro model of
      tight (> 2,000 ohm-cm2) rat alveolar epithelial cell monolayers grown on tissue
      culture-treated polycarbonate filters. METHODS: Unidirectional HRP fluxes were
      estimated from the appearance rate of HRP in the receiver fluid following
      instillation in the donor fluid as a function of donor [HRP] and temperature.
      Molecular species present in either bathing fluid were determined at the end of
      flux experiments using fluorescein isothiocyanate (FITC)-labeled HRP by gel
      permeation chromatography. Cell-associated HRP activity at the end of the
      transport experiment was determined, as were the rates of recycling and
      transcellular movement of HRP. An enzymatic assay was uses to quantify HRP
      activity in the bathing fluid and cells. RESULTS: Unidirectional HRP fluxes were
      symmetric and increased linearly with up to 50 microM donor [HRP]. The apparent
      permeability coefficient of HRP was reduced by 3.5 times upon lowering the
      temperature from 37 to 4 degrees C. About 50% of the FITC-labeled species present
      in either receiver fluid was intact HRP. Cell-associated HRP estimated from
      apical HRP incubation was about 4 times greater than that from basolateral
      incubation. Recycling into apical fluid of cell-associated HRP following apical
      incubation occurred rapidly with a half-time (T1/2) of approximately 5 min,
      reaching a plateau at approximately 67% of the initial cell-associated HRP, while
      transcellular movement of HRP (into basolateral fluid) took place with a T1/2 of
      approximately 20 min, attaining a steady-state at approximately 13% of the
      initial cell-associated HRP. Basolateral recycling of HRP was also rapid (T1/2 =
      approximately 5 min) reaching a steady-state at approximately 35% of the initial
      basolaterally-bound HRP. Transcellular movement of HRP following basolateral
      incubation was slower (T1/2 = approximately 70 min), leveling off at 50% of the
      initial cell-associated HRP. CONCLUSIONS: HRP appears to be transported
      relatively intact (approximately 50%) across rat alveolar epithelial barrier via
      nonspecific fluid-phase endocytosis. The transepithelial pinocytotic rate of
      alveolar epithelial cells is estimated to be about 25 nL/cm2/h.

PMID- 9026794
TI  - [The significance of exacerbations of lung diseases in the development of chronic
      cor pulmonale and their treatment].
AB  - In 61 patients, pulmonary tuberculosis was complicated by thrombosis of the
      pulmonary artery or its embolism and by bronchial asthma. In various lung
      diseases, there was a combination of some factors predisposing to chronic cor
      pulmonale. These included specific infection, sympathoadrenal activation, reduced
      capillaries, and hypoxia in pulmonary tuberculosis, alveolar hypoventilation with
      arteriolar spasms, and elevated intrathoracic pressure in bronchial asthma;
      higher pulmonary arterial systolic pressure due to spasms of the pulmonary
      branches and drastically reduced arterial bed in pulmonary thromboembolism.

PMID- 9026795
TI  - [The diagnostic potentials of the method for the intradermal administration of
      denatured gamma-globulin in coniotuberculosis of the intrathoracic lymph nodes].
AB  - A direct relationship exists between coniotuberculosis of occupational origin,
      thoracic lymph node coniotuberculosis in the elderly and frequency and intensity
      of the body response to intracutaneous administration of denatured gamma-globulin
      (DNGG). Positive DNGG test is a nonspecific test for dust content,
      anthracosilicotic induration and coniotuberculosis of thoracic lymph nodes. As
      additional to clinicoroentgenological examination of thoracic lymph node
      coniotuberculosis of occupational and non-occupational origin.

PMID- 9026796
TI  - [The differential diagnostic characteristics of sarcoidosis of the intrathoracic
      lymph nodes and of cardiovascular diseases].
AB  - One hundred and fifty-four (5.7%) of 2690 patients who had been admitted to a
      hospital for sarcoidosis of intrathoracic lymph nodes (ITLN) were diagnosed as
      having various cardiovascular diseases (hypertensive disease, congestive lung,
      congenital and acquired cardiac diseases, atherosclerosis, aortic aneurysms and
      myocarditis). Misinterpretation of the X-ray film of the lung root, no lateral X
      ray films, inadequate scope of objective studies of the cardiovascular system are
      the most common errors at prehospital examination. The obligatory making of
      lateral X-ray films, tomograms, the use of computed tomography, ECG and
      phonocardiography, and thorough account of objective data are valuable additional
      methods in the differential diagnosis of ITLN sarcoidosis and cardiovascular
      diseases accompanied by the appearance of wide truncal large vessels of the root
      due to pulmonary hypertension.

PMID- 9026797
TI  - [The current aspects of the recurrence of tuberculosis of the respiratory organs
      in adults].
AB  - Data on the incidence of recurrent respiratory tuberculosis in the Russian
      Federation from 1978 to 1993 were analysed in 1165 adult patients with recurrence
      and 2017 tuberculosis-cured patients. In the vast majority of patients (97-98%),
      steady-state clinical healing of tuberculosis can be achieved with its favourable
      clinical course and adequate treatment. This is evidenced by comparatively few
      relapses (6-7 per 100,000 adult persons). Among all varieties of relapses, late
      recurrences make up 74.7-81.2% and occur on the average 9.7-13.1 years after the
      completion of complex treatment. Comparison of the incidence of clinical types of
      pulmonary tuberculosis, used treatment regimens and methods has demonstrated that
      the clinical course of a late recurrence did not differ from that of the first
      diagnosed tuberculosis. It is expedient to recognize late recurrence to be
      essentially a new case of pulmonary tuberculosis. This suggests that the concept
      of recurrence, the pathogenesis of late recurrence, the form and content of work
      with registered outpatients should be reviewed.

PMID- 9026798
TI  - [The characteristics of the bacterial flora in patients with interstitial lung
      diseases].
AB  - The paper deals with a possible contribution of microorganisms to the development
      of interstitial pulmonary diseases (IPD). An examination was made of 57 patients
      who were in terms of nosological entities were divided into 3 groups: 1) patients
      with fibrotic alveolitis; 2) those with pulmonary sarcoidosis, and 3) those with
      histiocytosis X. All patients underwent general clinical examinations,
      microbiological studies of bronchial contents, mainly bronchial swabs. Based on
      the examinations and studies, it may be concluded that the infectious component
      is not the leading predictor of IPD development. However, it should be borne in
      mind that some patients, those with pulmonary sarcoidosis in particular, have a
      pneumococcal infectious process.

PMID- 9026799
TI  - [The immediate and late results of the surgical treatment of patients with
      complicated forms of pulmonary tuberculosis].
AB  - Immediate and long-term outcomes of repeated and multistage operations were
      analyzed in 190 patients with pulmonary tuberculosis. The aspects of work
      rehabilitation were studied in these patients. The efficiency of repeated and
      stage surgical interventions in patients both with disseminated and complicated
      types of tuberculosis and with pleural empyemas and in those with uncomplicated
      postoperative disease is 87.5 and 92.2%, respectively. The long-term results
      indicated that the complete clinical effect preserved in 79.2% of patients. Work
      rehabilitation was achieved in 64.8% of the examinees in the long-term
      postoperative period. The use of repeated and stage surgical interventions in
      patients with pulmonary tuberculosis may rehabilitate a rather large proportion
      of those operated on, assuming a great socioeconomic significance.

PMID- 9026800
TI  - [A comparison of clinico-scintigraphic studies with the morphological changes in
      the lungs in destructive tuberculosis].
AB  - Radionuclide findings were compared with morphological changes in resected lung
      tissue in 78 patients with destructive tuberculosis. In the preoperative period,
      30 (38.5%) of 78 patients were found to have significant and much significant
      changes in regional blood flow while 48 (61.5%) patients had restrictive changes.
      This provides evidence that 76% of the first diagnosed patients with destructive
      pulmonary tuberculosis had chiefly inflammatory changes, i.e. the specific
      process was reversible and only 24% had sclerotic changes. In patients with
      chronic destructive tuberculosis, sclerotic pulmonary and inflammatory changes
      were prevalent in 73.6 and 26.4%, respectively. Scintigraphic studies are of
      great clinical and diagnostic value of characterizing the extent and site of a
      pathological process in patients with pulmonary tuberculosis, revealing regional
      circulatory disorders both at the site of a specific process and in the intact
      areas of the lung, as evidenced by morphological studies.

PMID- 9026802
TI  - [Caseous pneumonia in nursing and young infants (based on pathomorphological
      study data)].
AB  - Fifty-six autopsy protocols showing the presence of caseous pneumonia in babies
      and infants who died in 1947-1994 were examined. In the age group of children who
      died from caseous pneumonia (n = 88), babies and infants made up 63.6%. In 1947
      1962, caseous pneumonia was found to frequently complicate a primary tuberculosis
      process both in babies (28.3%) and in 1-3-year-old infants (22.2%). At the same
      time lifetime tuberculosis was not recognized in 21.4% of cases and 26.8% died
      within the first 3 days of their hospital stay.

PMID- 9026801
TI  - [The pathoanatomical,diagnosis of progressive forms of pulmonary tuberculosis in
      relation to the new clinical classification].
AB  - This communication is a letter of information that gives for postmortem diagnosis
      a brief account of tuberculous inflammation and major types of pulmonary
      tuberculosis during their progression to death and an approximate outline of
      pathoanatomical diagnosis. Terminal tuberculosis is shown to be now complicated
      by miliary and caseous pneumonias. Caseous pneumonia may appear as an independent
      nosological entity and as a complication of acute progression, more frequently,
      of fibrocavernous tuberculosis. Caseous pneumonia as a tuberculosis type is an
      irreversible process that calls for emergency surgical treatment. It has been
      found that there are primarily impairments in lung connective tissue function,
      acute mesenchymopathy with high blood barrier permeability in caseous pneumonia.
      Terminal bronchiolar lesion is a later stage in the pathogenesis of caseous
      pneumonia.

PMID- 9026803
TI  - [A genetic pool study of the population of the Republic of Tyva using genetic
      markers for the search for associations with tuberculosis].
AB  - Eighty three Tyvin patients with local pulmonary tuberculosis and 295 healthy
      donors of the same nationality were examined. They are resided in the central
      area of Tyva (in Kyzyl and its vicinities). In addition, 132 healthy Tyvin
      Todjins were examined. Tuberculosis mortality was found to be associated with the
      antigen HLA-B15 in the Tyvins living in the central area of the Republic of Tyva
      (Kyzyl). The incidence of HLA antigens and polymorphic protein locus genotypes
      varies in different areas of the Republic of Tyva.

PMID- 9026804
TI  - [Changes in the microflora of the sputum and the bronchoalveolar fluid in
      patients with acute and protracted pneumonias].
AB  - A quantitative technique was used to microbiological study of sputum in 110
      patients with acute pneumonia and 56 with advanced pneumonia, in 38 of them,
      their bronchoalveolar lavage fluid was simultaneously examined. In acute
      pneumonia, Pneumococcus was most commonly (71.8%) cultured, frequently in
      combination with other microorganisms, mainly with Neisseria and
      Enterobacteriaceae. These patients were found to have higher pneumococcal
      cultivation rates (83.0%) in the bronchoalveolar lavage fluid. Following 3 weeks
      of etiotropic therapy, the pneumococcal cultivation rates dropped to 10.8%.
      Pneumococcus also occupied the leading place (69.6%) in the etiology of advanced
      pneumonia, Mycoplasma pneumoniae was detected by the indirect immunofluorescence
      test in 28.5% of patients. After 3-week therapy, the cultivation rates for
      Pneumococcus decreased to 23.0%, its association with other microbes being more
      frequently observed. At the same time there was a rise in the detection rate of
      Mycoplasma antigen, which could cause advanced pneumonia.

PMID- 9026805
TI  - [The composition of the cerebrospinal fluid in children with tuberculous
      meningitis with different patterns of the mycobacterial population].
AB  - Composition of the liquor with regard of mycobacterial population was
      investigated in 113 children with tuberculosis meningitis. The changes in the
      liquor were most pronounced in bacterial variant of the causative agent and were
      minimal in the absence of both bacterial and L-forms of M. tuberculosis. This,
      however, does not mean that tuberculosis etiology of meningitis is ruled out.

PMID- 9026806
TI  - [Free-radical processes in the pulmonary macrophages of patients with pulmonary
      tuberculosis].
AB  - Free radical processes in the alveolar and interstitial macrophages were compared
      for patients with different forms of tuberculosis, chronic nonspecific pulmonary
      diseases and cancer of the lungs. Alveolar macrophages were found to have more
      active free radical processes than interstitial macrophages. Chronic
      transformation of pulmonary tuberculosis results in activation of free radical
      processes in pulmonary macrophages. Differences in the value of alveolar
      macrophages chemiluminescence maximum and time of its appearance may facilitate
      differential diagnosis between tuberculosis, chronic nonspecific pulmonary
      diseases and cancer of the lungs.

PMID- 9026807
TI  - [Middle molecules and tuberculosis activity in children and adolescents at the
      sanatorium stage of treatment].
AB  - Medium-weight molecules (MWM) were measured in the plasma of 67 children and
      adolescents aged 11 to 17 years who were infected with and suffered from various
      types of tuberculosis. The highest values of MWM were found in patients with
      tuberculous exudative pleuritis and infiltrative pulmonary tuberculosis. During
      treatment, there was a significant reduction in the mean levels of MWM in 20
      follow-up patients. It is concluded that it is expedient to employ this test to
      detect insidious tuberculosis activity during sanatorium treatment and to use it
      as a criterion for therapeutical efficiency.

PMID- 9026808
TI  - [The risk group in the contingents of a correction institution: the structure and
      procedure for its observation].
AB  - Studies were made of the structure of individuals with residual pulmonary changes
      who were at corrective labour institutions. Among them, the incidence of active
      tuberculosis is 16-21 times greater than that of reactivation among the other
      populations. It is these persons who should be regarded as a risk group and
      regular prophylactic measures should be used in them.

PMID- 9026809
TI  - [The immunomodulating action of cyclosporin A in vitro and in vivo on the
      lymphocytes of patients with alveolitis].
AB  - The paper presents the first results of using cyclosporin A (CsA) to treat
      lymphocytes during their extracorporeal immunomodulation (EIL) in patient with
      fibrotic alveolitis of various etiology. Two-hour lymphocytic incubation in the
      medium containing 0.1-10 micrograms per ml of CsA was sufficient for CsA to show
      its in vitro immunosuppressive effect, which resulted in a substantial inhibition
      of a proliferative lymphocytic response to mitogens and antigens. Administration
      of CsA-treated lymphocytes induced no profound structural changes in lymphocytic
      subpopulations (CD3, CD4, CD8), but it was followed by a reduction in the
      baseline high proliferative lymphocytic response to PHA. The clinical effect,
      alveolitis alleviation was noted in all patients. It is suggested that clinical
      effects may be produced by a local concentration of the treated lymphocytes and
      their transferred CsA as well.

PMID- 9026810
TI  - [Tuberculomas of the lungs (a lecture)].

PMID- 9026812
TI  - [A case of ulcerative tuberculosis of the stomach in a patient with multiple
      pulmonary tuberculomas].

PMID- 9026811
TI  - [Experience in treating tuberculosis patients suffering from alcoholism at a
      sanatorium].

PMID- 9026813
TI  - [A pleural-pulmonary syndrome in liver cirrhosis].

PMID- 9026814
TI  - [The lipid and carbohydrate components of mycobacteria and the methods for their
      determination].

PMID- 9026815
TI  - [An analysis of primary tuberculosis infection and the infection rate in children
      in tuberculosis foci].
AB  - The paper presents data on primary infection and infection rates of children from
      contacts with tuberculosis and from the healthy environment. The infection rates
      of the contacted children is 3.4 times higher, especially in infants and
      preschool children. It also shows factors predisposing to infection: asocial
      families when the patient shows his physician's noncompliance, the lack of
      revaccination in children and drug prevention. In 25.6% of children, infection
      had been detected before they were found to have contacts with a tuberculosis
      patient, and examinations of the infected child's environment made it possible to
      detect an adult tuberculosis patients. By and large, in 1994 the detection rate
      of tuberculosis in adults among children with primary infection was 7.4 per 1000
      examinees in Kazan, which is 10 times higher than that at mass fluorography of
      the adult population.

PMID- 9026816
TI  - [The procedure for the differentiated hypoglycemic therapy of diabetics
      hospitalized for pulmonary tuberculosis. The Central Research Institute of
      Tuberculosis of the Russian Academy of Medical Sciences, Moscow].

PMID- 9026817
TI  - [3rd International Conference on AIDS, Cancer and Related Problems (22-26 May
      1995)].

PMID- 9026818
TI  - [Morbidity and the organization of antiepidemic and prophylactic measures in
      illness in children in an environment with tuberculosis patients].
AB  - Data on tuberculosis morbidity rates in children and on main preventive measures
      (vaccination, revaccination, etc.) in Udmurtia. Over 5 years, the morbidity rates
      of children contacting with Mycobacterium tuberculosis-isolated and Mycobacterium
      nonisolated individuals were 1215.4 and 1432.1, respectively. An analysis of the
      types of tuberculosis of sick children established that tuberculosis of the
      intrathoracic lymph nodes was prevalent (63.1%). The children having familial
      contacts for 6-12 months fell ill more frequently. Timely isolation of children
      and adolescents at the sanatorium-type institution is of beneficial value among
      measures for familial focal sanitation, in addition to specific prophylaxis.

PMID- 9026819
TI  - [The skin tuberculin sensitivity of students at the Astrakhan Medical Institute
      and its dynamics over the course of 36 years (1957-1993)].
AB  - More than 10,000 first-to-sixth year students have undergone the Mantoux test
      (MT) for 36 years. Before 1980, the tuberculin sensitivity of the students
      declined rapidly (as high as 3% per year), then more slowly (1%), persons with
      tuberculin hypersensitivity reduced in number, and the previously observed rise
      in the proportion of tuberculin-positive persons among the first-to-second year
      students becoming fourth-to-sixth year ones. Recently, the number of MT-positive
      students has stopped increasing, but there has been a growth in the share of
      persons with an indurate of MT with 2 TE in 10-20 min (from 36.1e4.0 to
      51.3e4.0%) with the still permanent proportion of tuberculin-hypersensitive
      students and without any increase in the incidence of tuberculosis among pupils.
      The authors hold that this phenomenon is the first sign of poor epidemiology. In
      this connection, they consider that mass MT with 2 TE performed in individuals
      with an indurate of above 10 mm is noteworthy as this is a growth index of the
      specific sensitization of the population and they are to be systematically
      tested.

PMID- 9026820
TI  - [Utilization of different microbiological markers in the study of Haemophilus
      influenzae].
AB  - The present study includes 178 Haemophilus influenzae strains isolated in
      different pediatric hospitals from Havana, Cuba, during 1991-1994, associated to
      divers infections (meningitis, respiratory sepsis, primary bacteremia). A
      combination of various typing and subtyping methods was used as epidemiological
      markers: serotyping (slide agglutination with diagnostical serum a-f and latex
      agglutination), biotyping according to Killian's procedures (by determination of
      indole production, urease and ornithine decarboxylase activity), subtyping by
      fermentative profiles according to Roberts' methods (glucose, maltose, xylose and
      fructose) and outer membrane protein profile subtyping (vesicles extraction by a
      modified Barenkamp's method, analysis by lineal and gradient SDS-PAGE and
      assessment according to our own classification system). Serotype b was identified
      in 89.3%, biotype I was the most frequent (79.1%), other biotypes (II, III, IV
      and V) were also identified. Fermentative profile D (glucose, maltose, xylose and
      fructose positive) was the most frequent (52.8%) while profile G (glucose,
      maltose, xylose positive and fructose negative) represented 20.2%. Other known
      profiles were present. PA2 (33.7%) was the most frequent OMP subtype. Even though
      11 different protein subtypes were found, the 77.5% of the strains were located
      in only three OMP electrophoretic subtypes (PA2, PC1, LA2).

PMID- 9026821
TI  - [Poly-(3-hydroxybutyrate) granules in Bacillus megaterium. Isolation and analysis
      of associated proteins].
AB  - Bacillus megaterium accumulates poly-(3-hydroxybutyrate) (PHB) as a reserve
      material in intracellular granules. In this work we described a method for the
      preparation of PHB granules from B. megaterium PV447 and the analysis by
      polyacrylamide gel electrophoresis of the associated proteins. By comparison with
      another species a function is proposed for some of these proteins.

PMID- 9026822
TI  - [Determination of serum aminoglycoside and vancomycin concentrations by the
      microbiological method in the presence of other antimicrobials].
AB  - The determination of serum concentrations of antimicrobials with a narrow
      therapeutic range by microbiological method requires some modifications when the
      patient is under combined antimicrobial therapy. The methodological conditions
      for the appraisal of aminoglycosides and vancomycin in the presence of other
      drugs were evaluated by using strains with selective sensitivity to the
      antimicrobial to be tested or by the adding crude extracts of beta-lactamases for
      the inactivation of the beta-lactam antimicrobials. These beta-lactamases were
      obtained from Enterobacter cloacae P99 (derepressed mutant) cultures for the
      inactivation of penicillins and first, second and third generation
      cephalosporins, as well as from Stenotrophomonas (Xanthomonas) maltophilia M 1484
      cultures for the hydrolysis of imipenem. The strains allowing vancomycin
      appraisal and indifferent to the synergic activity of other drugs in the mixture
      were S. aureus M 2120, when the accompanying antimicrobials were gentamicin,
      ciprofloxacin or rifampicin, and E. faecalis M 2113, E. avium M 2091 and S.
      aureus M 2101 when the drugs in the mixture were amikacin, lincomycin or
      trimethoprim-sulfamethoxazole, respectively. For the appraisal of gentamicin in
      the presence of vancomycin or fluoroquinolones (ciprofloxacin or norfloxacin), E.
      coli M 1376 was the most suitable strain, while the use of K. pneumoniae ATCC
      10031 was required for the appraisal of amikacin or netilmicin. When rifampicin
      was the accompanying antimicrobial, E. coli M 1495 turned out more adequate. E.
      coli M 1462 proved to be more satisfactory for gentamicin, amikacin and
      netilmicin dosages in samples also containing chloramphenicol, trimethoprim
      sulfamethoxazole or tetracycline.

PMID- 9026824
TI  - [Molecular characterization of HTLV-II from an intravenous drug addict with AIDS
      in Argentina].
AB  - Ten intravenous drug user AIDS patients were studied to determine the presence of
      HTLV-I/II infection. Sera were screened by particle agglutination test and by an
      in house indirect immunofluorescence assay using MT2 (HTLV-I) and C19 (HTLV-II)
      producing cell lines. Out of the ten sera, one was confirmed HTLV-II positive by
      Western blot. Peripheral blood mononuclear cells were obtained from this patient,
      separated through a Ficoll-Hypaque gradient and DNA was extracted and amplified
      by semi-nested PCR. The amplified product obtained was cloned and sequenced.
      Results demonstrated the presence of HTLV-II proviral DNA and comparison of the
      obtained sequence with different HTLV-II prototypes led to classify the virus
      into subtype a. This is the first molecular characterization of HTLV-II in an
      intravenous drug user in Argentina.

PMID- 9026823
TI  - [Cellulolytic activity of coprophilic fungi].
AB  - Fourteen isolates, members of the Ascobolaceae family, representing two
      widespread genera, Ascobolus and Saccobolus, were obtained from dung of
      herbivorous animals. All the isolates were capable of growing and producing
      clearing zones in CMC agar media. The species of Ascobolus gave larger clearing
      zones than the species of Saccobolus. S. verrucisporus and S. longevisporus were
      the most cellulolytic species in this genera while A. bistisii was the most
      cellulolytic among all the species tested. The results obtained showed that more
      than one method of screening must be employed to analyse the cellulolytic ability
      of different species.

PMID- 9026825
TI  - [Cross-reactivity between Chlamydia psittaci and Acinetobacter in indirect
      immunofluorescence assays].
AB  - Cross reactivity between Chlamydia psittaci and a strain from genus Acinetobacter
      was investigated by indirect fluorescent antibody (IFA) technique. Two groups of
      serum samples were tested: 64 belonged to patients diagnosed as psittacosis and
      64 (control group) were non reactive to Chlamydia psittaci by IFA. Samples were
      incubated on smears prepared with an Acinetobacter suspension for detecting IgG
      and IgM. 100% reactivity to IgG was found in 1:16 serum dilution among anti
      psittacosis sera, whereas 6.25% of control sera reacted at the same dilution.
      When testing IgM, high rates of reactivity were found in both serum groups, thus
      it has been discarded as a marker for cross reactivity. Fluorescence pattern
      suggests that antigens are located at the cell wall.

PMID- 9026826
TI  - [Mycotoxin-producing fungi in foods].
AB  - This is an overview of the most important toxicogenic species of molds that
      contaminate human food and animal feed. Effects of fungal secondary metabolites
      are described. Attention is focused on toxicogenic species of Aspergillus,
      Penicillium and Fusarium. Species of other genera reported as toxicogenic are
      also considered.

PMID- 9026827
TI  - [Conditions for the laboratory survival of Haemagogus janthinomys dyar, 1921
      (Diptera:Culicidae)].
AB  - A little modification was made on the classical Borel tube, used for rearing
      isolated females of mosquitoes. The first studies were realized with the main
      Yellow fever vector, Haemagogus janthinomys, in Brazil. The results are: a better
      survival, as far as 72 days, a greater number of eggs, up to 80, and a shorter
      trophogonic cycle of 7-8 days. So, one can imagine more easily further studies
      about the vertical transmission of the YF virus by this important neo-tropical
      mosquito.

PMID- 9026828
TI  - [Outbreak of acute toxoplasmosis transmitted thru the ingestion of ovine raw
      meat].
AB  - The authors present 17 cases of symptomatic acute toxoplasmosis acquired by the
      ingestion of raw mutton offered during a party in September 1993. The incubation
      period carried from 6 to 13 days (10.9 +/- 7.0). Sixteen (94.5%) patients
      presented fever, headache, myalgia, arthralgia, and adenopathy (cervical or
      cervical/axilar). Hepatomegaly was found in 6 patients, splenomegaly in 4 and
      rash in 2. One patient presented clinical picture of chorioretinitis confirmed by
      ophthalmological exam. All patients showed increased serum levels of specific
      antibodies (IgG and IgM) on indirect immunofuorescence assay evidencing acute
      phase of toxoplasmosis. The patients were treated with specific drugs for
      toxoplasmosis and presented satisfactory clinical and laboratory response.

PMID- 9026829
TI  - [Detection of Aedes aegypti and Aedes albopictus, in an urban zone of the
      municipality of Catanduva, SP, after control of a Dengue epidemic].
AB  - After the realization of control research that had in view the transmission of
      dengue virus, we started to monitor two kinds of entomological vigilance, Breteau
      Index and ovitrap. We intended to evaluate the necessary time elapsed before
      Aedes sp mosquitoes were again detected at the urban area of Catanduva s town
      (SP). The ovitraps showed positiveness for the Aedes aegypti two months after the
      control research, while the Breteau Index became positive only at the fourth
      month after the end of the referred research.

PMID- 9026830
TI  - [Use of new tools for controlling triatomines in different entomologic situations
      in the American continent].
AB  - The field results of new tools for triatomine control developed under the
      sponsorship of WHO/TDR are reported: a) A slow-release "paint" containing
      malathion; b) fumigant cans containing cypermethrin and DDVP, and c) sensor boxes
      for the detection of triatomine infestations. Field assays were performed in
      Chile, Honduras and Paraguay against Triatoma infestans, T. dimidiata and
      Rhodnius prolixus, accordingly to a standard protocol designed by a WHO experts
      committee. Preliminary 6 months post-treatment results for the three countries
      show an efficient control when insecticide paints were used indoors and in the
      peridomicilium, keeping reinfestation near zero. The final results presented for
      Chile two years post-treatment confirmed the superiority of the slow-release
      "paints". Sensor boxes were less effective than man/hour captures in the
      detection of infested houses.

PMID- 9026831
TI  - [Spotted fever in the municipality of Pedreira, PS, Brazil. Serologic survey].
AB  - Cases of Brasilian spotted fever (BSF) have been occurred since 1985, in the
      rural area of Pedreira town, situated 160 km away from the city of Sao Paulo
      (longitude 46 degrees 54'07", latitude 22 degrees 44'21"). Aiming at evaluating
      the prevalence of Brasilian spotted fever in this endemic area, single-serum
      samples were collected from 473 healthy persons, amongst city-dwellers and the
      local china industry workers. The obtained samples were tested by indirect
      immunofluorescence (IFA), in order to determine the antibodies titer for the
      group of Brasilian spotted fever. Twenty-five (5.3%) were considered positive
      (titer 3 1:64) and thirty-one (6.5%) were taken as "borderline" (titer 1:32). The
      results show a serologically positivity rate similar to other areas, known as
      endemic ones within the country.

PMID- 9026832
TI  - [On the reversal of schistosomiasis hepatic fibrosis after specific therapy.
      Histopathologic study].
AB  - Surgical liver biopsies of patients of both sexes, between 18 and 72 years old,
      with the compensated hepatoesplenic form of schistosomiasis mansoni, previously
      treated with oxaminique (Mansil) were studied by histological and
      immunohistochemical methods. Although the search for parasites and/or granulomas
      was negative in all specimen studied, the portal fibrosis remained.

PMID- 9026833
TI  - [Cutaneous lesions as the only manifestations of reactions to Trypanosoma cruzi
      infection in a recipient of a kidney transplant].
AB  - We report a patient with chronic asymptomatic Chagas' disease that presented
      Trypanosoma cruzi reactivation after kidney transplantation and immune
      depression. The only clinical manifestation of the disease was ulcerative skin
      lesions, which is unusual in Chagas' disease.

PMID- 9026834
TI  - [Intestinal entomothoramycosis: report of a case].
AB  - A case of intestinal entomophthoramycosis caused by Entomophthorales in a man
      with 19 years-old, farmer and without associated disease. The patient was
      submitted to a intestinal resection and diagnosis was carried through after
      analysis of the surgical specimen. After a review of the literature, the clinical
      evolution, clinico-pathologic features, difficulties in diagnosis and treatment
      are discussed.

PMID- 9026835
TI  - [Preliminary activities of the program for the control and treatment of
      onchocerciasis in the Yanomami territory, Roraima, Brazil].
AB  - After to characterize the clinic and epidemiological picture of the
      onchocerciasis in Yanomami region, RR, Brazil, begun in 1993, the National Health
      Foundation (FNS) implemented a Control and Treatment Pilot Project in Tootobi and
      Balawau. Here, it was studied skin biopsies from 426 inhabitants. In the nodules
      of 86.7% from patients was encountered Onchocerca volvulus. The over-all
      prevalence in the examined population was 66.2%. The treatment with ivermectin
      covered 80.1% of total population. Adverse reactions, light and moderate, of the
      medicament were reported in 12.3% of the patients. These results agreeing with
      the medical literature and suggesting the viability of to increase of the
      programme for all Yanomami area in the next phase.

PMID- 9026836
TI  - [The polymorphism of the angiotensin I-converting enzyme gene and its association
      with ischemic cardiopathy].
AB  - The role played by angiotensin in the development of coronary heart disease is a
      subject of increasing interest. This interest is due to the results of several
      trials suggesting that treatment with angiotensin I-converting enzyme inhibitors
      decrease the incidence of clinical manifestations of coronary heart disease. The
      relationship between angiotensin and coronary heart disease is being analyzed
      both from basic and clinical approaches. As a result of such investigations, a
      polymorphism in the angiotensin converting enzyme gene has been described and the
      role of this polymorphism as a possible risk factor for coronary heart disease
      has been reported. In this paper the current knowledge about the angiotensin
      converting enzyme gene is reviewed and its relationship with coronary heart
      disease is discussed.

PMID- 9026837
TI  - [Thromboendarterectomy as a treatment for chronic pulmonary hypertension].
AB  - Chronic pulmonary hypertension is an extremely difficult disease to diagnose and
      is usually identified by the exclusion of other more recognized causes of
      enlargement in mean pulmonary arterial resistance. Up to now, treatments proposed
      for this disease, have not been very successful. Medical procedures are not a
      long term proper solution which leads the process to an irreversible point whose
      only solution should be a pulmonary transplantation. In recent years, study
      groups have established a surgical method, alternative to transplantation, which
      has been able to increase, with a decrease in mortality rates, a longer and a
      better quality of life for the patients affected by this disease: we are talking
      about pulmonary thromboendarterectomy.

PMID- 9026838
TI  - [Left ventricular structure and (systolic and diastolic) function in hypertensive
      patients without atherosclerotic coronaropathy].
AB  - INTRODUCTION AND OBJECTIVES: Electrocardiographic (ECG) ST-T segment
      abnormalities in hypertensive patients are traditionally associated with
      hypertrophy and/or ischaemia and a higher cardiovascular risk. Hypertensive
      patients with typical or non-typical chest discomfort and a normal
      coronarographic study underwent an echocardiographic and Doppler study in order
      to assess left ventricular structure and (systolic and diastolic) function.
      MATERIAL AND METHODS: Hypertensive patients with ST-T changes were classified as
      follows: Control group (CG) was made up of 12 hypertensive patients (6 women, 6
      men, mean age 59.6 +/- 7.4 years) with normal ECG; Group A (GA), 10 patients (6
      women, 4 men, mean age 63.1 +/- 6.8 years) with ECG image of strain; Group B (GB)
      (9 women and 8 men, mean age 61.3 +/- 10.1 years) with other ST-T alterations. We
      assessed by echocardiographic and transmitral flow Doppler study left ventricular
      structure and (systolic and diastolic) function. RESULTS: Interventricular septum
      thickness, left ventricular posterior wall thickness, left ventricular mass and
      mass index were significantly higher in the GA and GB than in the CG, without
      differences between GA and GB groups. No differences in left ventricular systolic
      function parameters were observed between the groups. In comparison with the CG,
      the GA and GB showed significant differences in E wave deceleration velocity and
      deceleration time, A wave deceleration time and isovolumetric relaxation time.
      Between GA and GB differences were observed in A wave deceleration time and
      isovolumetric relaxation time. CONCLUSIONS: In hypertensive patients without
      atherosclerotic coronaropathy, ST-T changes identify a group with greater left
      ventricular mass and worse left ventricular diastolic function. The patients with
      a ST-T strain pattern showed the impaired diastolic function.

PMID- 9026839
TI  - [Disease of the left coronary trunk. Our experience. An analysis of surgical
      morbimortality].
AB  - INTRODUCTION AND OBJECTIVES: The superiority of surgical treatment over other
      procedures in the left main coronary artery stenosis is well known, being today
      the therapy of choice. The purpose of this work is to analyze the clinical
      characteristics and the immediate results of surgery in our patients. PATIENTS
      AND METHODS: In this paper we under-took a retrospective study of 147 consecutive
      patients, 129 men and 18 women with a 50% or more left main coronary artery
      stenosis without associated valvular disease, operated on at our institution
      during a period of 3.5 years, between January 1992 and May 1995. Thirty-one
      variables were analyzed under Chi-square, comparison of proportions and Student's
      t-tests. Then, it has been developed into a multivariant logistic regression of
      significant variables (p less than 0.05) of factors influencing mortality and
      rhythm disturbances which have been the most frequent postoperative complication.
      RESULTS: The mean age was 65 years. Sixty-two per cent had unstable angina and
      51.7% had previous myocardial infarction. An average of 3.1 grafts were
      performed. Total mortality was 6.8%. The complications were 17% arrhythmias, 8%
      low cardiac output and 6% perioperative myocardial infarction. In the
      multivariate analysis, mortality has been strongly related to the presence of
      perioperative myocardial infarction and also with moderate to severe cardiomegaly
      and a high left ventricular end-diastolic pressure. Arrhythmias were related to
      an advanced age. CONCLUSIONS: 1) In hospital mortality remains within acceptable
      limits and is influenced by the presence of perioperative myocardial infarction,
      cardiomegaly and a high left ventricular end-diastolic pressure, and 2) elderly
      patients have more damaged vessels, more diseased coronary segments, and more
      complications, especially rhythm disturbances.

PMID- 9026840
TI  - [A comparison of bezafibrate and lovastatin treatment at the usual doses in post
      heart transplant hyperlipemia].
AB  - INTRODUCTION: Coronary artery disease is a major limiting factor for long-term
      survival after heart transplantation. Hyperlipidemia is a probable risk factor
      for coronary artery disease in this kind of patient. Bezafibrate and lovastatin
      have proved to be effective in lowering total and low density lipoprotein
      cholesterol. The present study tested the safety and efficacy of both drugs on
      lipid levels in 21 patients with post-heart transplantation hyperlipidemia.
      PATIENTS AND METHODS: Patients maintained the same diet for three months. Then,
      they were randomized to lovastatin (20 mg/day) or bezafibrate (400 mg/day) for 8
      weeks, and then, crossovered to an additional 8 weeks of bezafibrate or
      lovastatin. RESULTS: Both drugs were effective in lowering total and low density
      lipoprotein cholesterol and apoprotein B concentrations, but the effect of
      lovastatin was significantly greater. Only bezafibrate produced a significant
      reduction in total triglycerides and a significant rise in high density
      lipoprotein cholesterol and apoprotein AI. The total cholesterol/high density
      lipoprotein cholesterol and low density lipoprotein cholesterol/high density
      lipoprotein cholesterol ratios were decreased under both treatments. CONCLUSION:
      Both drugs, bezafibrate and lovastatin appear to be safe, effective and well
      tolerated therapies for hyperlipidemia in cardiac transplant recipients.

PMID- 9026841
TI  - [Growth factors and mitogenic activity in experimental hypercholesterolemia].
AB  - INTRODUCTION: Hypercholesterolemia is associated with increased platelet
      reactivity and changes in megakaryopoiesis, which might influence the synthesis
      of growth factors in the megakaryocyte. MATERIAL AND METHODS: 20 miniature pigs
      were randomly assigned to received 18 weeks of either regular pig chow feed
      (control group, n = 10) or a high cholesterol diet (cholesterol group, n = 10).
      Platelet count, mean platelet volume, platelet distribution width and bleeding
      time were determined in both groups. Intraplatelet and serum mitogenic activity
      was quantified by Swiss 3T3 and vascular smooth muscle cells proliferation
      assays. Insulin-like growth factor I and platelet-derived growth factor (BB
      isoform) levels were quantified in platelet lysates and in serum in both groups.
      RESULTS: Hypercholesterolemia was associated to a significant decrease in mean
      platelet volume and bleeding time, but it did not affect the proliferative effect
      of serum and platelet lysates nor its growth factor content. CONCLUSIONS: Taken
      together, our results suggest that although hypercholesterolemia affects platelet
      reactivity, its atherosclerosis-promoting effects cannot be explained by a direct
      effect on vascular smooth muscle cell proliferation or by changes in serum or
      intraplatelet growth factor content.

PMID- 9026842
TI  - [Research methods in clinical cardiology (II). Observational studies (II):
      natural history and prognosis in cardiology. Methodology].
AB  - Epidemiology has been defined as "the study of the distribution and determinants
      of disease frequency in human populations". Therefore, epidemiology has developed
      study design strategies to provide different approaches to research etiology and
      causal inference. Among the analytic observational studies, prospective cohort
      designs are mainly used to test epidemiologic hypotheses. This paper describes
      the basic concepts of the design, conduct, analysis, and interpretation of these
      studies, we have emphasized the unique strengths and limitations of the cohort
      study design that must be taken into account.

PMID- 9026843
TI  - [Sinus bradycardia secondary to systemic pentamidine].
AB  - Systemic side effects caused by parenteral pentamidine are frequent. They can be
      severe and life-threatening. Intravenous pentamidine may cause a variety of
      abnormalities in the cardiac conduction system as tachyarrhythmias, hypotension
      and/or non-specific ECG changes (a long corrected QT interval). There is only one
      case of previously reported bradyarrhythmias in an HIV-infected patient. We
      present a new adverse effect associated with intravenous pentamidine therapy, and
      to the best of our knowledge, this is the first reported case of sinus
      bradycardia in a patient who is not HIV-infected.

PMID- 9026844
TI  - [Aortico-left ventricular tunnel associated with pulmonary valve stenosis].
AB  - Aortico-left ventricular tunnel is an unusual cardiac anomaly. The main clinical
      feature is early, severe aortic regurgitation, and surgical management is
      mandatory. Exceptionally this defect is associated with pulmonary valve stenosis.
      A case of a newborn with aortico-left ventricular tunnel plus pulmonary valve
      stenosis is reported. Initially she underwent percutaneous pulmonary
      valvuloplasty during diagnostic cardiac catheterization and with surgical closure
      of the tunnel later.

PMID- 9026845
TI  - [Minimally invasive coronary surgery. Thoracostomy-assisted thoracotomy. Apropos
      a case].
AB  - CLINICAL CASE PRESENTATION: Male, 62 years old with progressive angina. Positive
      stress test. At catheterization a proximal 90% stenosis of the LAD was found. Not
      suitable for PTCA. SURGICAL TECHNIQUE: Double lumen endotracheal tube was
      inserted. Position was 30 degrees right lateral decubitus. The thoracoscope was
      introduced through the 7th intercostal space and a minithoracotomy was done. The
      internal mammary artery (IMA) was dissected partially through direct vision and
      partially with the help of the thoracoscope. The IMA graft was implanted to the
      LAD without cardiopulmonary bypass with a segmentary occlusion of the vessel with
      tourniquets. EVOLUTION: Thoracic drainage 575 cc, CK/MB 311/5, final hematocrit
      37%. No blood transfusion. Dismissed on the 5th postoperative day.

PMID- 9026846
TI  - [Aortic valve replacement via ministernotomy].
AB  - Minimally invasive cardiac surgery is arising as an alternative technique in some
      cardiac operations. We present the first aortic valve replacement via
      ministernotomy. We describe in detail the technique of ministernotomy and the
      limitations that this new approach would have. We conclude with the advantages of
      minimally invasive cardiac surgery over conventional approach and review other
      techniques described in the literature.

PMID- 9026848
TI  - [Some proposals for the next 50 years].

PMID- 9026847
TI  - [Depressed conduction and increased automaticity in acute septal myocardial
      infarct].

PMID- 9026849
TI  - [Tuberculosis and immigrants. A study of its prevalence in the Umbria region].
AB  - In 1995, 463 patients were admitted in the medical service of Perugia (Sanitary
      District n. 6). Only 20% of them were enrolled in the TBC programme. Mantoux was:
      < 10 mm in 35%, 10-15 mm in 25%, > 15 mm in 40%. Chest Rx in 30 subjects
      demonstrated: normality in 19; old TBC in 7, active TBC in 4 (miliary, bilateral
      upper lobe pneumonitis, left subapical upper lobe pneumonitis and right lobitis
      of the upper lobe). All patients were admitted in hospital and showed positive
      sputum culture for Mycobacterium Tuberculosis. They were treated with isoniazid,
      rifampin, pyrazinamide, ethambutol/streptomycin for 2 months and with isoniazid,
      rifampin for other 4-8 months. Two patients showed Mycobacterium tuberculosis
      with isoniazid resistance. Seven patients were treated with isoniazid
      chemoprophylaxis without side effects. Migrants should receive information about
      health care service and be encourage to register themselves with a general
      practitioner. Skin test screening and chest radiographs for those with positive
      results should be provided at a convenient location.

PMID- 9026850
TI  - [Hypertensive cardiac damage in heart transplantation. A noninvasive monitoring
      study of arterial pressure].
AB  - This study is aimed at investigating the relationship between cardiac hypertrophy
      and blood pressure (BP) 24-h pattern in 34 heart transplanted patients (HTP), 9
      out of them (26%) being considered as normotensives, the other ones (74%) being
      regarded as hypertensives under adequate treatment, via casual sphygmomanometry.
      The study is an attempt to explain the occurrence of at least one sign of
      hypertrophic cardiopathy in 20 cases (59%), hypothesizing the presence of false
      normotensives among the putative normotensives and presumably-cured
      hypertensives. The ambulatory BP monitoring was able to identify 7 hypertensives
      (78%) among the putative normotensives, and 17 not well-cured subjects (68%)
      among the presumably cured hypertensives. At least one sign of cardiac
      hypertrophy was found in 5 (50%) of the 10 true normotensives, who were all non
      dipper, and in 15 (63%) of the 24 hypertensives. The 9 hypertensives without
      cardiac hypertrophy (37%) had developed hypertension very recently. These
      findings stress the role of the ambulatory BP monitoring as a diagnostic tool
      during the follow-up of HTP, in order to identify the false normotensives as well
      as the not well-treated hypertensives. This role can contribute to optimize the
      prophylaxis of hypertensive damage for the transplanted heart.

PMID- 9026851
TI  - [Prognostic factors in acute nonlymphoid leukemias].
AB  - Our retrospective study was aimed at assessing parameters affecting the prognosis
      of acute non lymphoid leukemia (ANLL). Since 1988 to 1994 we observed 84
      patients: 52 males, 32 females. For each patient we considered at diagnosis: age,
      fever, performance status, platelets, hemoglobin and white blood cell count,
      extramidollary disease, bone marrow blastosis, phenotype and cytogenetic
      abnormalities of blasts cells. All the parameters listed above were correlated
      with the time to achieve the complete remission (CR), CR duration and the overall
      survival. Statistical tests as t-student and chi square test were used.
      Statistical analysis of the parameters considered revealed that the only value
      affecting the achievement of a CR was the age. The prognostic significance of
      immunophenotyping in ANLL has been a controversial issue, with a number of
      conflicting reports. In our study only the terminal deoxynucleotidyl transferase
      was significantly associated with prognosis. Our study, as data reported in
      literature, confirms that the prognostic impact of the various parameters in ANLL
      is controversial. The study of prognostic factors and of the immunophenotype is
      important to identify the clinical and the biologic profile of the disease and to
      evaluate the optimal post-remission treatment.

PMID- 9026852
TI  - [Neuro-SLE. Models of its clinical expression].
AB  - In this paper we considered different models concerning the clinical expression
      of neuropsychiatric involvement in course of systemic lupus erythematosus (SLE).
      These models describe pathological conditions as multifocal cerebropathy,
      transverse myelitis, peripheral neuropathy and panic attacks. We have chosen
      these cases as clinical example of different pathogenic mechanisms responsible of
      CNS-lupus, as hypercoagulation due to antiphospholipid syndrome, immune-complex
      vasculitis, complement-mediated autoantibody damage and antibody-induced
      cytotoxicity. The prevalence of neuropsychiatric manifestations in 122 SLE
      patients is also reported. Finally, the paper reports some guidelines about
      diagnostic and therapeutic behaviour in course of CNS-lupus.

PMID- 9026853
TI  - [Primary thrombocythemia in a female carrier of IgA deficiency].
AB  - We describe a case of essential thrombocythemia observed in a 67-year-old woman
      with severe IgA-deficiency. The the best of our knowledge, this is the first
      report concerning the onset of a chronic myeloproliferative disease (CMPD) in a
      patient affected with primary immunodeficiency, in particular IgA-defect. The
      association may be merely coincidental; otherwise hemopoietic growth factors
      acting on myeloid progenitor cells could play a role in this relationship. It has
      recently been shown that serum levels of many cytokines are elevated in patients
      with CMPD and probably contribute to enhance proliferation of the malignant
      clones; on the other hand interleukin-6 seems to account for reactive
      thrombocytosis, and significant amounts of circulating interleukin-4 and
      interleukin-6 have been detected in IgA-deficient patients. Overproduction of the
      two cytokines may depend on recurrent infections, but it could also represent a
      primary abnormality, with a putative role in the pathogenesis of the immune
      defect. These findings suggest that high levels of growth factors could induce
      myeloid hyperproliferation and so expose stem cells to genetic mutations
      responsible for malignant transformation.

PMID- 9026854
TI  - [The treatment of serious autoimmune diseases. Immune ablation integrated with
      hematopoietic stem cells].

PMID- 9026855
TI  - [The re-emergence of tuberculosis: the endemia of multiple-antibiotic-resistant
      strains].

PMID- 9026856
TI  - [The arterial prothrombotic state and the plurimetabolic syndrome].

PMID- 9026857
TI  - [The medical therapy of chronic pancreatitis. Problems, progress and outlook].
AB  - The aims of medical therapy in chronic pancreatitis are mainly to relieve the
      recurrent pain and to correct any malabsorption secondary to digestive
      insufficiency resulting from deficient exocrine pancreatic function. The
      treatment of the pain initially involves the use of dietary measures and
      analgesic drugs. The results of the use of pancreatic extracts and somatostatin
      reported in the literature are controversial, as are those of coeliac plexus
      block. Of unquestionable efficacy, at least in the short to medium term, are
      surgical decompression interventions in patients, with pain refractory to these
      measures and who present significant dilation of Wirsung's duct at ERCP.
      Endoscopic decompression constitutes an alternative to surgical decompression. In
      view of the transitory results of endoscopic decompression, which, in any event,
      should be implemented only by endoscopists possessing the necessary experience
      and expertise, the use of this technique may perhaps be targeted at carefully
      selected patients to be submitted to surgical decompression. As far as
      maldigestion is concerned, which occurs only when the pancreatic functional
      deficit reaches 90% or more, replacement therapy with pancreatic extracts must be
      resorted to. Multi-Unit Dose preparations are to be preferred, consisting in
      gastro-protected microspheres measuring not more than 2 mm in diameter and
      containing high doses of lipase, since at least 30,000 I.U. of lipase are
      required in the post-prandial phase for reasonably satisfactory correction of the
      steatorrhoea. Should this fail to prove effective, it is good policy to add
      antisecretory drugs (H2-antagonists, proton-pump inhibitors).

PMID- 9026858
TI  - [The immunological activity of corticosteroids].
AB  - Corticosteroids are among the most used anti-inflammatory and immunosuppressive
      drugs. The most recent reports have shown that the corticosteroids: A) modulate
      the lymphocyte recirculation and induce a lymphocyte depletion mainly regarding
      to the CD4 cells. B) Inhibit several lymphocyte activities, as well as their
      capacity to secrete cytokines and their clonal expansion under activating
      conditions. C) Induce apoptosis in primed T cells. D) Modulate the synthesis and
      activity of nuclear factors AP1 and NFkB. Moreover several data suggest that the
      molecular manipulations of cortisol, performed with the aim of improving its
      therapeutic efficiency, might change its capacity to bind the cytoplasmic
      receptor and/or generate CTS/CTS-R compounds that have different capacity to
      migrate through the nuclear membrane and/or to activate the nuclear responsive
      elements inducing different biologic responses.

PMID- 9026859
TI  - [Updates on equine trichinellosis].
AB  - Trichinellosis is a zoonosis caused by parasites of the genus Trichinella.
      Transmission of trichinellosis to humans has been shown to occur mainly by the
      ingestion of meat from pigs, bears of foxes parasitized with muscle larvae of
      this parasite. However, in Europe, the major human outbreaks of the disease have
      occurred due to the ingestion of parasitized horse meat. Although the larvae were
      not isolated from the horse meat, the identification of larvae as T. nativa, T.
      britovi and T. spiralis was done in biopsy samples obtained from infected
      individuals. More recently T. spiralis muscle larvae have been isolated and
      identified, for the first time, in muscle tissue of horses slaughtered at an
      abattoir in the State of Mexico. Furthermore, in ELISA assays using total
      extracts or TSL-1 antigens, circulating antibodies against Trichinella have been
      detected in horses slaughtered at abattoirs from various countries in Europe and
      Mexico. On the other hand, the experimental infection of horses with parasites of
      the genes Trichinella has been achieved by several research groups and data
      obtained regarding the kinetics of antibody production in these animals are
      important in the development of sensitive and specific diagnostic assays for
      horse trichinellosis. This will allow to determine the frequency of this
      infection in horses which are used for animal and human feeding. These assays
      will also be very helpful for designing strategies to control transmission on the
      disease by horse meat.

PMID- 9026860
TI  - [Microsporidiosis: current state of a new parasitosis].
AB  - Protozoa of the order Microsporida have become regarded as causes of several
      pathologies in patients with severe immunodeficiencies. Apparently they are
      transmitted to the human through fecalism, but also the respiratory route has
      been considered. People most affected are young males infected with the human
      immunodeficiency virus. The most important genera are: Enterocytozoon,
      Encephalitozoon, Septata, Nosema and Pleistophora. There are discrepancies about
      the biology of these parasites and little is known of their behavior in the human
      host. It is concluded that with the advent of AIDS, many nosological entities by
      opportunistic organisms, that were not previously considered as human infections
      are appearing. This work is a review of the literature published from 1959 to
      1995, related to epidemiological, clinical, diagnostic and therapeutic aspects.

PMID- 9026861
TI  - [Cochlear implant. Indications and counterindications].

PMID- 9026862
TI  - [Cochlear implants. Auditory evoked potentials. Role of the operating room
      nurse].

PMID- 9026863
TI  - [Cochlear implant. Anesthesia].

PMID- 9026865
TI  - [Cochlear implant. Management of implantation].

PMID- 9026864
TI  - [Cochlear implant. Surgical intervention. Role of the operating room nurse
      (circulating and instrumentalist)].

PMID- 9026866
TI  - [Iatrogenic tracheal stenosis. Anatomic and etiologic review].

PMID- 9026867
TI  - [Iatrogenic tracheal stenosis. Prevention of iatrogenic complications].

PMID- 9026868
TI  - [Iatrogenic tracheal stenosis. Materials necessary for treatment].

PMID- 9026869
TI  - [Iatrogenic tracheal stenosis. Anesthesia].

PMID- 9026871
TI  - [Patient form. Tracheal prosthesis. Orders for monitoring].

PMID- 9026870
TI  - [Iatrogenic tracheal stenosis. Treatment and monitoring].

PMID- 9026873
TI  - [The auditory apparatus and the cochlear implant].

PMID- 9026872
TI  - [Obstetric surgery. Cesarean section and episiotomy].

PMID- 9026874
TI  - [Cochlear implant. Preoperative assessment].

PMID- 9026875
TI  - [What is your diagnosis? Persistent incomplete omphalomesenteric duct].

PMID- 9026876
TI  - [Steps to integration or the fight with the Hydra "dualism"].
AB  - Dualism in medicine (making a sharp distinction between somatic and psychosocial
      features) is not based on human nature. Rather, it is the result of the
      development and training of the observer. A physician must be brought to realize
      this. For behind his every medical consideration and action lies a medical
      theory. Clinical examples are given, where the physician's lack of awareness of
      the limitations of his concept led to serious results for the patient. The author
      describes his own path through training and experience from dualism to an
      integrative biopsychosocial concept. Based on his own pain research, he shows how
      results depend on the concept followed. He insists that from the very beginning
      medical studies must be founded on a biopsychosocial model.

PMID- 9026877
TI  - [Cardiac complications in adult diphtheria: analysis of 212 cases].
AB  - In a series of 212 cases of diphtheria toxica in adults 90 (42%) suffered from
      cardiac complications. While early clinical signs were lacking or unspecific, the
      diagnosis could be suspected based on changes in the ECG. The earliest signs were
      sinus bradycardia, AV dissociation, AV escape rhythmus, prolongation of QT
      interval and large U wave (U > T, T + U wave). In cases where the differential
      diagnosis of myocarditis and other heart diseases in adults is difficult,
      attention should focus in the sickle-like depression ('sagging') of the ST
      interval, which is a typical sign for diphtheric myocarditis. It occurs even in
      the presence of pre-existing left-ventricular hypertrophy or bundle branch block.
      The severest forms of diphtheric myocarditis are complicated by AV and
      intraventricular conduction disturbances and malignant ventricular
      tachyarrhythmias.

PMID- 9026878
TI  - [Regazell-Energen: bioactivator in tumor treatment? Documentation No. 26 D].
AB  - Regazell-Energen (RE) is a combination of drinking vials which contain gelee
      royale, ginseng, hawthorn, wheatgerm extract solved in mead, and capsules filled
      with mixed pollen. RE is recommended for revitalization and regeneration,
      regulation and stimulation of the immune system and in the early metaphylaxis of
      treated cancer patients. Two courses during 40 days per year should be taken. RE
      has practically no side effects. Only individuals with pollen allergy or alcohol
      intolerance should be cautious. A package for a 14-day course costs 170 Swiss
      francs. RE is produced by Bio-Naturkraft in Poing, Munich, and research is
      supported by the German Society for Matrix Research. The president is Prof. H.
      Heine from the Institute of Anatomy of the anthroposophic University Witten
      Herdecke. The bioactivator RE ist claimed to be a 'new, autonomous therapeutic
      system' to 'increase physical and mental well-being ... helping to overcome
      stress and immune defects'. Heine claims that RE acts decisively on the
      'regulation of the matrix' and fights cancer by activating the fibroblast
      macrophage system via the healthy tissue. The three clinical investigations on
      the effect of RE in the oncological aftercare contain severe flaws in the
      collection of data and interpretation.

PMID- 9026879
TI  - [Epidemiological study of sleep disorders in patients in Swiss general practice].
AB  - The aim of the study was to assess the prevalence, severity, associated factors
      and diagnosis of sleep disorders in general practice. Over 700 patients were
      investigated with a multiple choice questionnaire in 24 general practices in
      Switzerland. To assess sleep disorders, criterion A for insomnia according DSM
      III-R was applied. The prevalence of sleep disorders was 44%, 64% of these were
      classified as mild, 31% as moderate and 5% as severe. 50% of the female patients
      complained about insomnia compared to 36% in males. Retrospectively, 74% of the
      patients stated having suffered from sleep disorders for more than one year (mild
      76%, moderate 69%, severe 75%). 70% of patients with mild, 42% with moderate and
      30% of patients with severe insomnia didn't inform their physicians about their
      sleep difficulties on the occasion of an earlier consultations. Patients with
      moderate or severe insomnia felt moderately or markedly disabled in their quality
      of life (71%) and work (58%). To estimate general anxiety and depressive state,
      self-rating scales were used (STAI, D-S). In comparison to reference values for
      healthy volunteers, insomniac patients had significantly higher scores on both
      scales, which were associated with the severity of sleep disorders, corroborating
      the association of sleep disorders with anxiety disorders and depressions. The
      physicians diagnosed in 18% of insomniacs a psychiatric disease, in 52% a
      psychoreactive disorder and in 26% a somatic etiology. The study shows that sleep
      disorders are a frequent syndrome in general practice and often not reported to
      the physician; therefore, the patients should routinely be questioned about sleep
      problems, and associated psychiatric diseases should be considered.

PMID- 9026880
TI  - [A case from practice (369). 1. Acute gastroenteritis. 2. Oral candidiasis].

PMID- 9026881
TI  - [A case from practice (370). Rectal foreign body].

PMID- 9026882
TI  - [History of the beginning of radiology in Lausanne (1896-1921)].

PMID- 9026883
TI  - [Early management of closed dysraphism in children. Value of urodynamic and
      manometry studies].

PMID- 9026884
TI  - [Ovarian hernia in girls].

PMID- 9026885
TI  - [Malnutrition in children and the variability of drug effects].

PMID- 9026886
TI  - [Propofol is toxic for immature GABAergic neurons].

PMID- 9026887
TI  - [High frequency oscillatory ventilation in pediatrics].

PMID- 9026888
TI  - [Cortisone and children].

PMID- 9026890
TI  - [Liaison child psychiatry in neonatology].

PMID- 9026889
TI  - [The kidney in children under chemotherapy].
AB  - Nowadays more and more children survive after an intensive anti-tumoral therapy.
      The price to pay consists of numerous and relatively frequent long-term sequelae
      (secondary tumors, neuropsychological deficits, endocrine or cardiac damage).
      After chemotherapy, we sometimes observe renal side-effects, either tubular
      (metabolic acidosis, hypokalemia, hypomagnesemia, proteinuria, Fanconi syndrome,
      rickets) or glomerular (acute or chronic decreased GFR). These renal toxic side
      effects are encountered especially after cisplatinum and ifosfamide, less
      frequently after carboplatin and cyclophosphamide. The pediatrician has to be
      aware of these toxic nephrologic side-effects, to look out for them and monitor
      carefully the renal function of all paediatric patients receiving these
      potentially nephrotoxic chemotherapies.

PMID- 9026891
TI  - [Nitrilotriacetic acid (NTA)--properties and environmental behavior. II.
      Ecotoxicity and biodegradability of NTA in the environment].
AB  - The results are described of studies on the effects of NTA on aqueous organisms
      and crops. The results show that NTA at concentrations determined in natural
      water systems causes no disturbances of the equilibrium in ecosystems. The
      conditions of the NTA biodegradation process in communal sewage and in surface
      waters and the effects of the processes taking place in water treatment systems
      destined for providing drinking water on NTA degradation are described. In a
      summary of the results of monitoring studies conducted in countries where NTA has
      been accepted for widespread use in washing powders the problems are stressed
      which will require solving before the decision is made of permission of NTA use
      in Poland. As of now, there are no full data making possible permission of using
      NTA in products of household chemistry.

PMID- 9026892
TI  - [Investigation on spatial distribution of chloronaphthalenes in flounder
      Platychtis flesus from the gulf of Gdansk].
AB  - Flounders from the three different and relatively distant sites in the Gulf of
      Gdansk were collected in august and october 1992 and analysed to investigate a
      potential differences in concentration and composition of chloronaphthalenes. The
      method of PCNs measurement was capillary gas chromatography and high resolution
      mass spectrometry (HRGC/HRMS) after a nondestructive extraction and cleanup step
      via dialysis with polyethylene membrane and than HPLC preseparation on a
      activated carbon column. Chloronaphthalenes were separated and quantified on RTx
      5 capillary column using an electron impact (EI) mode and selective ion recording
      (SIR). All samples contained detectable concentrations of many tetra-, penta- and
      heksachloronaphthalenes, and the total PCNs concentration ranged from 1700 to
      3900 pg/gwet weight. A substantial difference in pattern and concentration of
      PCNs residues in flounders between some of the sampling sites were found.

PMID- 9026893
TI  - [Polychlorinated naphthalenes in Harbour porpoises Phocoena phocoena].
AB  - Concentration and composition of chloronaphthalenes (PCNs) were determined in
      blubber of two male and two female porpoises from the Gulf of Gdansk. Porpoises
      examined died in the fishing nets in 1992. Polychlorinated naphthalenes were
      determined using capillary gas chromatography and high resolution mass
      spectrometry (HRGC/HRMS) after nondestructive cleanup with polyethylene membrane,
      and pre-separation of planar compounds on carbon HPLC column. 28 peaks from
      chloronaphthalenes were identified and quantified on a chromatogram.
      Concentration of total PCNs in blubber of male porpoises were 1.7-2.4 ng/glipid
      weight, and of female 2.0-2.4 ng/g. Among of the PCN congeners found 1,2,3,4,6,7
      /1,2,3,5,6,7-hexachloronaphthalene (PCN nr 66/67) and 1,2,4,6-/1,2,5,7
      tetrachloronaphthalene (PCN nr 3/34/37) were dominating compounds, followed by
      1,4,6,7-tetrachloronaphthalene (PCN nr 47), 1,2,3,5-/1,3,5,8
      tetrachloronaphthalene (PCN nr 28/43) and 1,2,3,5,7-/1,2,4,6,7
      pentachloronaphthalene (PCN nr 52/60), and others were minor contributors.

PMID- 9026894
TI  - [Evaluation of a detection method for determination of aflatoxins in peanuts
      using immunoaffinity chromatography coupled fluorimetry detection].
AB  - The aim of the study was determination of the basic analytical parameters of the
      AFLATEST method (accuracy, precision, recovery) and testing of its usefulness in
      concentrations down to 10 mu/kg. In the test the studied extracts are purified
      passing them through columns with monoclonal antibodies, followed by fluorimetric
      determination after reaction with bromine solution. The capacity and the
      efficiency of the columns were tested and fluorimeter calibration was checked.
      The reliability of the method was assessed fortifying a series of arachids
      samples with aflatoxin B1 and determining then recovery and precision. The
      accuracy of the method was checked by determination of certified reference
      standard. In the light of the obtained results the AFLATEST method was found to
      be applicable for semiquantitative determination of aflatoxins in arachids in the
      concentrations above 5 mu/kg.

PMID- 9026895
TI  - [Measurements of radon 222Rn in water from the deep borehole in Warsaw].
AB  - Radon 222Rn in deep borehole water in the Warsaw's district has been quantitative
      determined. The measurements were performed using the alpha liquid scintillation
      counting method. The measurements results were compared to the 222Rn
      concentration limit in drinking water approved in other countries. In some cases
      the concentrations of 222Rn in investigated water samples exceed 11 Bq/l. The
      annual radiation dose equivalent received by the people consuming every day such
      water in Warsaw in about 0.014 mSv (1.4 mrem).

PMID- 9026896
TI  - [Evaluation of the health aspects of goat milk].
AB  - The work contains results of determinations of protein, fat, lactose, vitamin C
      and minerals: Ca, P, Fe, Mn, Cu, Zn, Na, K, Cl as well as toxic metals like Hg,
      Cd and Pb in goat milk. The nonmineral components were determined by general
      approved analytical methods. Minerals like Ca, P, Fe, Mn, Cu, Zn, Na, K, Cd and
      Pb were determined by the flame ASA method and mercury by "cold vapour"
      technique. Chloride were determined by Mohr method and phosphorus as phosphates
      by colorimetric method with ammonium molybdate. Mean percentage content of
      protein, fat, lactose and ash were: 3.2 (range 2.7-3.7); 3.9 (3.2-6.5); 4.1 (3.9
      4.9); 0.87 (0.84-1.00) respectively. Mean content of ascorbic acid amounted 0.53
      mg/100 g (range 0.19-1.42), and the content of minerals were as follows: Ca 130
      (range 102-150); P 127 (115-151); Mg 14.1 (12.6-16.3); Mn 0.026 (0.019-0.037); Cu
      0.04 (0.02-0.08); Zn 0.54 (0.40-1.25); Fe 0.047 (0.020-0.097); Na 42.4 (20.8
      59.5); K 163 (138-190); Cl 168 (128-180). The levels of toxic metals were mostly
      below the allowable limits, mercury from 3.8 to 14.5 micrograms/kg, cadmium <
      0.01 micrograms/kg. In the case of lead a 40% of investigated samples were above
      the allowable limits.

PMID- 9026898
TI  - [Choice of media for detection of Streptococcus faecalis in routine water
      testing].
AB  - The aim the study was to find a medium for routine water testing for detection of
      Streptococcus faecalis which could be used by water supply laboratories and
      sanitary services. In the study dry ready Merck media were used: Mf-enterococcus
      agar, MF-enterococcus agar base, K-F-streptococcus agar, and Azide Nutrient Pad
      Sets (of Sartorius). The Slanetz-Bartley medium prepared in our laboratory
      National Institute of Hygiene (PZH). Method served as control. The usefulness of
      media for the isolation of Str. faecalis was tested in waters of household wells
      in the environs of Warsaw. Water from 50 wells was tested; from each well two
      samples of 10 ml and 100 ml were filtered. The filters were placed on the tested
      media and incubated at 37 degrees C for 48 hours. Colonies with characteristic
      pink or orange brown colour were counted. From each plate 3-5 colonies were taken
      for verification tests. For verification tests 609 bacterial colonies showing
      characteristic growth on tested media were taken. For the statistical analysis of
      the results variance analysis was used which showed no significant differences
      between the control Slanetz-Bartley medium and the ready Merck media. These media
      can be used alternatively for routine water testing for detection of Str.
      faecalis. The Azide medium is not recommended since 96% of colonies showing in
      this test the growth characteristic of Str. faecalis were negative in
      verification tests. In routine water testing in case of growth of characteristic
      colonies on isolation media, it is recommended to carry out verification tests
      including, at least, a test for catalyse production, and culture on Litsky liquid
      medium or agar medium with bile salts and aesculin.

PMID- 9026897
TI  - [Nutrition and mortality from some diet-related diseases].
AB  - Authors analysed changes in consumption of selected food groups (cereals, fruit,
      vegetables, meat, fat, sweets) as well as mortality indexes (CVD, intestinal
      cancers, diabetes) among four European countries (the Netherlands, United
      Kingdom, Norway, Sweden) during 1970-1992. It was shown that consumption of fruit
      and vegetables (except the Netherlands) significantly increased. The growing
      tendency of meat consumption was decelerated, whereas no changes were observed in
      case of cereals, total fats and sweets. However (except Sweden) fats of animal
      origin decreased in favour of vegetable ones. As far as mortality from CVD and
      stomach cancer is concerned some decrease was observed in all countries. In
      addition mortality from intestine and colon cancer was lower in Sweden as well as
      UK. Although changes in dietary pattern are playing the crucial role observed
      mortality rates, other factors related to style of life incl. smoking or physical
      activity should not be overlooked.

PMID- 9026899
TI  - [Factors modulating the sensitivity of bacterial spores to steam under pressure].
AB  - The sensitivity of spores B. subtilis and B. stearothermophilus to steam under
      pressure depended on the growth medium and duration of cultivation. B. subtilis
      and B. stearothermophilus produced the largest number of spores on medium with Mn
      and yeast extract. However the spores grown on the medium were not the most
      resistant. The resistant spores was growing up with the age of cultures. The
      highest level of resistance was obtained in the case of the medium with Ca, after
      7-10 days of cultivation. The sporicidal effect of steam under pressure depended
      on the number of spores on the test.

PMID- 9026900
TI  - [Susceptibility of cockroaches Blattella germanica L. collected from hospitals to
      selected pyrethroid and carbamate insecticides].
AB  - The resistance to four pyrethroid insecticides: permethrin, deltamethrin,
      cypermethrin, etofenprox, and to two carbamate insecticides--bendiocarb, propoxur
      was investigated on field strains of German cockroaches (Blatella germanica L.)
      caught in hospitals from various parts of Poland. The tests were carried out only
      on males by the contact method recommended by the WHO. The resistance was
      evaluated on the basis of LT50S and resistance ratios (RRs). The tested fields
      strains showed high or moderate resistance to permethrin, deltamethrin,
      cypermethrin and bendiocarb: moderate resistance or tolerance to etofenproks
      (this compound has been never used in Poland before), and tolerance or
      susceptibility to propoxur.

PMID- 9026901
TI  - [Studies of the usefulness of Beauveria bassiana for eradication of cockroaches
      (Blattella germanica L.)].
AB  - The ability of killing cockroaches (Blattella germanica L.) by various strains of
      the mushroom Beauveria bassiana was studied, including also strains obtained by
      passaging. The study was conducted using adult insects, of varying age and sex,
      derived from laboratory cultures or caught in hospital rooms. The obtained
      results pointed out differences in the pathogenicity of B. bassiana strains for
      the studied populations of insects. The per cent of mortality among the insects
      depended on the pathogenic properties of B. bassiana strains, the density of
      mushroom spores in the food and on the sex of the insects. Passaging was found to
      be useful in case of strains with low pathogenicity for the insects since the
      passaged strains were more effective in their action on the insects than before
      passaging. Out of the studied strains the 23rd strain was most effective in
      reducing the number of the insects.

PMID- 9026902
TI  - [Some life style elements in students from public and non-public secondary
      schools].
AB  - The studies were performed on 825 school-children 16-17 years old (512 girls and
      313 boys) from first and second classes of secondary schools in some district
      towns in our country. 406 school-children attended public and 419 non-public
      schools. In the study was used a questionnaire worked out in the Institute for
      Children and Youth in Berlin. The analysis of the data collected by our co
      workers of the District Sanitary-Epidemiological Stations enable the following
      conclusions: In both groups of pupils from the public and non-public secondary
      schools similar abnormalities in their everyday life detrimental for health were
      found. Improper dietary habits, sleep deficits, short time for physical activity
      belonged to the most important and most frequent lifestyle abnormalities. 18% of
      the respondents went to school without eating breakfast at home, 19% took their
      breakfast not every day and 3% of the examined pupils don't eat breakfast at all.
      During the working-days 14% of pupils were eating no warm meal. This was the
      cause more frequent in pupils from non-public schools (19%) than from public
      schools (4%). 18% of the respondents were eating not always dinner on working
      days. 82% of pupils were going to bed too late: 49% after 10 o'clock p.m. and 34%
      after 11 o'clock p.m. Greater irregularities were found among boys (92%) than
      among girls (76%). 13% of pupils from the public and non-public schools spent
      only 30 minutes, the way to school included, in the fresh air and 54% pupils in
      the public schools and 43% in non-public schools--about 1 hour.

PMID- 9026903
TI  - Papers dedicated to Bjorn Henning Klevmark on the occasion of his 70th birthday
      August 16th, 1996.

PMID- 9026904
TI  - Use of ultra-thin window detectors for biological microanalysis.
AB  - Films and bulk samples of Nylon, gelatin, Makrofol, epoxy resin, aminoplastic
      resin and sodium acetate have been used as models of biological samples. It is
      shown that the use of ultrathin window (UTW) detectors in scanning transmission
      and scanning electron microsopes permits the quantitative analysis of light
      elements, yielding a total element analysis with hydrogen estimated by difference
      or "guesstimated". Comparison with known concentrations of concentrations
      obtained by chemical analysis shows that X-ray microanalysis of selections by the
      peak to continuum ratio model and bulk samples by the phi(pz) model gives
      sufficiently accurate results for biological purposes. It is also shown that
      sections may be analysed by the standardless ratio model. The application of UTW
      detectors to total element analysis by quantitative elemental imaging is
      demonstrated of bulk biological samples. which have been freeze-substituted,
      embedded in epoxy resin and surface polished. The possibility of imaging the
      oxygen content of frozen-hydrated bulk tissue samples which have been surface
      polished is also demonstrated. This may lead to the imaging of water distribution
      in frozen-hydrated bulk samples of biological tissues. UTW detectors are also
      useful for detecting mass loss in organic samples by monitoring the decrease in
      oxygen counts and for detecting contamination by monitoring the increase in
      carbon counts. It is also shown that changes in carbon counts are good indicators
      of folds in sections.

PMID- 9026905
TI  - Engery-filtering transmission electron microscopy of biological specimens.
AB  - By energy-filtering transmission electron microscopy (EFTEM) electrons can be
      separated by their energy losses. An electron-energy filter, added to the
      microscope column allows the measurement of the energy distribution of
      transmitted electrons that have lost energy (< 2,000 eV, with an energy
      resolution of approximately 1 eV). These filtered electrons, recorded either as a
      spectrum or as an image, are composed of two parts superimposed on top of each
      other: (a) the unspecific energy-loss population (= the continuum) and (b) the
      specific element-related energy-loss population (= the edges). At the edges,
      electron data in spectra and images are mathematically processed, to obtain the
      desired element-related net-intensity values or images. These data are related to
      the total transmitted electron intensity, from the zero- and low-loss spectral
      region giving the relative spectralor image intensity rations ((S)R*x, (I)R*x),
      which can be related to the element concentration. The acquisition of the zero
      loss and low-loss data is hampered by the restricted dynamic range of the TV
      camera. By improvements through the introduction of calibrated attenuation
      filters in the optical path to the TV-camera, more reliable values for (S)R*x and
      (I)R*x can be acquired. By addition of Bio-standards adjacent to the tissue, a
      "known" and "unknown" concentration of the element present in the same ultrathin
      section and the "bias" in the concentration estimation, can be obtained. Some
      practical examples are given for the estimation of the iron cencentration in
      siderosomes, boron in melasosomes and calcium in calcium oxalate monohydrate
      crystals.

PMID- 9026906
TI  - Sample preparation techniques for conventional and high resolution scanning
      electron microscopy of the central nervous system.
AB  - In the present paper some basic sample preparation techniques for scanning
      electron microscopy of nervous tissue are described. These basic preparative
      methods include conventional scanning electron microscopy or slicing technique,
      ethanol-cryofracturing technique, freeze-fracture method using either liquid
      nitrogen (slow freezing) or Freon 22 cooled by liquid nigrogen (fast freezing),
      improved freeze-fracture method with delicate specimen preparation and chromium
      coating, ultrasonic microdissection, and "creative tearing" technique. Some basic
      principles, advantages and limitations are critically considered. In addition,
      some specific applications in neurobiological research are reported. Emphasis is
      placed upon understanding the sources and nature of artifacts that are likely to
      be produced in each preparatory step. Examples are given of the results obtained
      with the different types of nerve tissue preparation, using the cerebellar cortex
      as a model of the central nervous system. According to the author's experience,
      the slicing technique is recommended for studying cytoarchitectonic arrangement
      of gray centers, the ethanol-cryofracturing technique for tracing short
      intracortical circuits, and the freeze-fracture methods for analysis of nerve
      cell cytoplasmic and nuclear compartments. An attempt is made to explain results
      obtained in relation with nerve cell biology.

PMID- 9026907
TI  - Evaluation of the use of tannic acid in preparation of the rabbit knee meniscus
      for scanning electron microscopy.
AB  - The femoral faces of medial and lateral menisci of the rabbit knee were
      structurally reinforced with tannic acid and studied using the scanning electron
      microscope. Significant improvement in preservation of the meniscal surfaces, as
      compared to previous studies, was brought about by the structural reinforcement
      technique. Menisci, although detacted from tibial plateaux, retained well their
      shape, dimensions, and microarchitecture. Differences in surface morphology
      between medial and lateral menisci and between longitudinal sectors on menisci
      were recorded. Appearances of surface irregulatities were reduced to a very low
      level, and the possibility that this minimum exists in situ is forwarded.

PMID- 9026908
TI  - [The biomechanics of the hip joint using new diagnostic aspects in the field of
      hip joint dysplasia. Constructive criticism of hip dysplasia diagnosis and
      present marketable breeding methods with an outlook on future perspectives and
      possibilities. Part I].
AB  - In absence of basic canine hip biomechanics, a specific, consequent three
      dimensional concept to evaluate the coxofemoral joint was developed for the dog.
      With the help of a new method to radiologically demonstrate the hip in a
      physiological standing position several new clinically relevant aspects could be
      further investigated. For example the breed specific anatomical differences in
      the hip, and dynamics and the background on "iatrogenic luxations" in HD
      diagnostics could be shown. The caudal luxation and the growth abnormalities of
      the hip and their consequences on the whole leg (antetorsion syndrome) as a
      consequence of inadequate breeding could be demonstrated.

PMID- 9026909
TI  - [Idiopathic epilepsy in the dog].
AB  - The clinical research results on idiopathic epilepsy (IE) in the dog performed at
      the Institute of Animal Neurology in Berne between the years 88-95 are presented.
      Special emphasis was placed on the genetic and electroencephalographic aspects
      obtained from large, uniform dog populations. We showed that IE affects all dogs
      of different ages. Although the clinical manifestation of seizure activity
      included different seizure types, a breed-specific seizure expression was found
      in the Retriever dog. Furthermore the use of interictal electroencephalography in
      the confirmation of IE was demonstrated. The results of a long-term treatment
      study with Phenobarbital in 46 Labrador Retrievers with IE are reported. In
      addition, the genetical and epidemiological aspects of the disease in each a
      large Golden and Labrador Retriever dog population were analysed.

PMID- 9026910
TI  - [The "activated coagulation time (ACT)": two simple screening methods for
      evaluating coagulation disorders in dogs].
AB  - The use of the activated coagulation time (ACT) for testing the intrinsic
      coagulation is well established among veterinary practitioners in the USA. The
      advantage of the ACT compared to other coagulation tests is its ease to be
      performed under practice conditions. The ACT may be measured manually or
      instrumentally. The reference range of our instrumental measurement is between 90
      and 120 seconds (median 105 seconds), of the manual measurement at room
      temperature between 115 and 145 seconds (median 125 seconds). Advantages of the
      instrumental method are the smaller amount of blood (0.4 ml versus 2.0 ml)
      necessary to perform the test, and the smaller potential for errors by
      unexperienced examiners. The spread is comparable between the two methods. The
      most important cause of false results is poor venipuncture technique: traumatic
      venipuncture will trigger the coagulation cascade already during venipuncture
      causing an artificially shortened ACT.

PMID- 9026911
TI  - [Monitoring of emergency and intensive care patients: simple diagnostic aids].
AB  - This article describes in short sections the use and interpretation of indirect
      blood pressure measurements, central venous pressure, body temperature, pulse
      oximetry, end tidal CO2 measurements, pulse and heart rate, urine production and
      emergency laboratory values. Most of these parameters are directly or indirectly
      linked to the perfusion of the patient. Optimizing these values are one of the
      most important goals in emergency and critical care medicine.

PMID- 9026912
TI  - [Differential diagnosis of resorptive tooth diseases and caries].
AB  - Feline Odontoclastic Resorptive Lesions (FORL, previously known as "neck
      lesions") on cat teeth are compared to caries and differentiated with the use of
      new methods. Radiological examination reveals typical odontoclastic resorptive
      processes, which take place at the dental root and at the periodontium. These
      lesions demonstrate the destruction on the desmodontium and the following
      ankylosing reaction. The rhodamine B stain which is selective for caries, stains
      regions which are softened by caries in a dark red way. Fuchsin/Acetic-Light
      Green stained histological preparations demonstrate the resorptive lacunae,
      resorptive lagoons and resorptive canals. Giant cells with multiple nuclei and
      reparative cementum can also be shown with the same stain. Hardness measurements
      using a Knoop diamond (KHN Knoop hardness number) give information about the
      degree of hardness of the different tissues. Electron microscopic investigations
      are performed to show the dentinal tubules and allowing the differentiation
      between FORL and caries. Since FORL also has been found in wild cats we deduced
      that alimentation has no effect on the pathogenesis of the disease.

PMID- 9026913
TI  - [Radiotherapy of pain in degenerative bone diseases].

PMID- 9026914
TI  - [Radiotherapy of primary cerebral non-Hodgkin's lymphoma].

PMID- 9026915
TI  - [Is transrectal sonography suitable for prevention?].

PMID- 9026916
TI  - [100 years use of roentgen rays in medicine--progress in radiology in 1896].

PMID- 9026917
TI  - [Kikuchi-Fujimoto necrotizing histiocytic lymphadenitis: disease or syndrome?].

PMID- 9026918
TI  - [Predeposit autotransfusion and the physiopathology of erythropoesis: an
      unsettled question].

PMID- 9026919
TI  - [Long-term culture: evidence of the capacity of stroma to sustain hematopoiesis
      of a second inoculum].
AB  - PURPOSE: To analyze, in two-stages long term bone marrow cultures (LTBMC), the
      efficiency of the method used for irradiation of the stroma and to check if after
      that, it's capable to support the hematopoiesis. MATERIAL AND METHODS: We have
      used for the first inoculum, bone marrow cells from eight controls. They were
      cultured at 2 x 10(6) cells/ml concentration until obtaining a fully confluent
      stroma which was irradiated with 15 Gy. After that, over this layer, we put a
      second inoculum with bone marrow cells in four cases, and with peripheral blood
      cells in four others, at a concentration of 1 x 10(5) cells/mL. In four cases the
      first inoculum was from a man and the second from a woman. The culture's
      haematopoietic activity was determined by the number of CFU-GM, total cell counts
      and the differential counts during four weeks. At the end of the study we
      recovered the cells from the supernatant of the culture and they were analyzed by
      in situ hybridization with an alpha centromeric probe specific to the X
      chromosome. RESULTS: In all cases we obtained a confluent stroma with production
      of haematopoiesis (cobblestone areas). The cells recovered at the end of the
      culture were, in all cases, from the second inoculum because they had a double
      signal with the X probe. The number of CFU-GM obtained was higher in bone marrow
      than in peripheral blood (34.5 and 9.2 respectively) however, the total cells
      were similar in both cases (2.3 x 10(5) and 2.9 x 10(5)) although the cellular
      subtypes varied depending on the second inoculum (B.M. or P.B.). CONCLUSION: Our
      data confirm that the dose of 15 Gy eradicate the haemopoiesis of first inoculum,
      which allowed to analyze stroma and progenitor cells, separately. In addition,
      the stroma is capable to support the hematopoiesis generated by progenitor cells
      from peripheral and bone marrow.

PMID- 9026921
TI  - [Histo-morphometry of bone mass and cellularity using image analysis:
      characterization of infiltration patterns in CLL].
AB  - PURPOSE: The aim of this study was to investigate a possible influence of
      lymphocytic infiltration in Chronic Lymphocytic Leukemia (CLL) on bone mass,
      according to the infiltration patterns. MATERIAL AND METHODS: We have studied
      histological preparations from decalcified and paraffin included bone biopsies
      and used a histomorphometric study through a mixed (interactive-automatic) image
      analysis, in order to quantify bone trabecular (BT/TV) and cellular volume (CV).
      Preparations were visualized via a 2.5 objective; a video camera was adapted and
      connected to a computer with analogical-digital converter incorporated. After the
      image was captured, a binarization was made by trabecular and medullary spaces
      segmentation; automatically, we calculated trabecular area (TA) and cellular area
      (CA). Expressions indicated above were used to calculate BV/TV and CV, expressed
      in percentage: BV/TV (%) = [TA/(TA + CA)] x 100, and CV (%) = [CA/(TA + CA)] x
      100. RESULTS: 92 normal biopsies and 79 CLL biopsies were studied (Nodular 12,
      Diffuse 22, Interstitial 23, Mixed 22). BT/TV in normal subjects age over 45, was
      18.40%; it was lower in CLL subjects, 17.25%. CV was 33.62% in normal cases and
      significantly higher in CLL with 42.95%. According to the infiltration patterns,
      Nodular pattern showed similar value to normal biopsies, versus Diffuse pattern
      with BT/TV of 16.19% and CV of 51.49%. Significantly, a high CV value was
      accompanied of a low B/TV value, in normal and CLL subjects. CONCLUSIONS: We
      analyzed histomorphometrically trabecular volume as expression of bone mass in
      undecalcified biopsies. CLL infiltration tended to show a lower trabecular
      volume. Diffuse pattern presented the higher cellular infiltration and bone mass
      destruction.

PMID- 9026920
TI  - [The fibrinolytic system in patients with dilated myocardiopathy].
AB  - OBJECTIVES: To study the fibrinolytic system in dilated cardiomyopathy (DCM)
      patients, and the relationship between the degree of severity (NYHA degree), and
      the presence of complications (atrial fibrillation, intracavity thrombus, and
      peripheral embolism). We also analyzed the influence of the antithrombotic
      therapy on the fibrinolysis's proteins. PATIENTS AND METHODS: We included 18
      patients, stratified in two etiologic groups: 9 with idiopathic and 9 with ethyl
      DCM. The fibrinolytic system was investigated through the plasma levels of
      antigenic and functional t-PA and PAI-1. We also carried out a venous occlusion
      test to investigate the fibrinolytic the fibrinolytic activity in t-PA secretion.
      The clinical aspects were recorded. We included 30 healthy individuals matched
      for age and sex, as controls. RESULTS: The antigenic levels of t-PA and PAI-1,
      were significantly higher in the DCM group than in the control group (p < 0.01).
      The venous occlusion test responses were normal. No relationship between the
      fibrinolytic parameters and clinical data were observed. DISCUSSION: The high
      levels of antigenic t-PA found in DCM patients were considered as a vascular
      injury marker, and a atherothrombotic risk factor. Furthermore, there is a
      hypofibrinolytic condition shown by a PAI-1 augmentation. In conclusion, we are
      prone to consider long term oral anticoagulation in the management of DCM
      patients.

PMID- 9026922
TI  - [Seroprevalence of hepatitis A in hemophiliacs].
AB  - PURPOSE: To study the seroprevalence of hepatitis A virus (HAV) infection in
      haemophiliacs treated with factor VIII/IX concentrates. PATIENTS AND METHODS:
      Anti-HAV IgG antibodies were tested in 133 haemophiliacs previously treated (20
      of them only infused with virus-inactivated factor concentrates), 11 previously
      untreated haemophiliacs and 60 healthy individuals (> 25 yr. old). RESULTS: The
      overall anti-HAV prevalence was 43%. Anti-HAV was found in 2 (10%) of the
      patients treated only with virus-inactivated concentrates and in 55 (49%) of
      those who had received non-inactivated concentrates. The seroprevalence in the
      untreated haemophiliacs was 27% and 90% in the healthy control group. The anti
      HAV seroprevalence showed a significant (p < 0.001) dependence on patient age, it
      being higher in patients aged > 25 (77%) than in those aged 10-25 (31%) and < 10
      (4%). The seroprevalence of anti-HAV was lower in the treated haemophiliacs aged
      25 or more than in the healthy individuals, although the difference did not reach
      statistical significance (p = 0.06). CONCLUSION: These results show that the
      seroprevalence of HAV infection in haemophiliacs is similar to that in the
      general population, and that there is not a significant excess of HAV infections
      amongst haemophiliacs with high exposure to coagulation factor concentrates.

PMID- 9026923
TI  - [B-cell lymphoma and low aggressiveness: from the historical paradigm of a
      clinico-biological entity to the challenge of an effective therapeutic strategy].

PMID- 9026924
TI  - [Kikuchi-Fujimoto disease associated with acute infection by herpesvirus 6].
AB  - The histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a very
      rare entity in Spain. We present a 34-year-old arabic male admitted to hospital
      because one-month story of asthenia, anorexia, weight loss, fever and
      lymphadenopathies in all palpable sites. Analytic studies were all within normal
      limits except LDH levels and globular sedimentation rate, both raised. After
      cervical lymph node biopsy performance high grade Non-Hodgkin lymphoma was
      initially diagnosed. During admission he complained from pain in both shoulders
      and an erythematous desquamative eruption in trunk appeared. Some days later, a
      second lymph node biopsy was performed and Kikuchi-Fujimoto disease was
      diagnosed. Serologic tests for human herpes virus 6 were positive demonstrating
      active associated infection. He begun treatment with indomethicin, fever and
      general symptoms disappeared one week later discontinuing treatment. Two months
      after discharge, all lymphadenopathies had disappeared. A review on
      epidemiological, clinical, pathological and differential diagnosis issues is
      made.

PMID- 9026925
TI  - [Chronic myeloid leukemia after renal transplantation: report of a new case and
      review of the bibliography].
AB  - The increase in cancer incidence in renal transplant recipients is a well
      recognized fact, which has been related to post-transplant immunosuppressive
      therapy. Solid tumors, skin cancer and non-Hodgkin's lymphomas account for most
      of the neoplasms in these patients, whereas chronic myeloproliferative disorders
      are infrequent. A patient is reported who developed chronic myelogenous leukemia
      (CML) six years after renal transplantation, which was followed by
      immunosuppressive with azathioprine, and the published data on such an
      association are reviewed. In all 10 cases reported azathioprine had been
      administered after transplantation. The amount and type of post-transplant
      immunosuppressive therapy seems to be the most important risk factor for the
      development of secondary CML in these patients, since no cases of CML in patients
      receiving cyclosporine A have been reported.

PMID- 9026927
TI  - [Detection of the Mbcr/abl translocation using FISH in bone marrow samples from
      patients diagnosed with CML and ALL].

PMID- 9026926
TI  - [Fungal infections in leukemic patients: our experience during 5 years].
AB  - The use of high-dose chemotherapy and the subsequent prolonged neutropenia in
      patients with haematological diseases have resulted in an increased incidence of
      fungal infections. These infections are associated with a high mortality rate.
      There are several predisposing factors including broad-spectrum antibiotic,
      central venous access. Diagnosis remains difficult. Characteristic clinical
      manifestations are not constant and they appear only after neutrophil recovery.
      Responsible organisms are infrequently isolated. The use of invasive procedures
      is far from being justified in patients who suffering usual severe
      thrombocytopenia. The unique drug with proven efficiency in the treatment of
      fungal infections is amphotericin B or liposomal amphotericin B. A favourable
      outcome strongly correlated with complete leukemia remission. We describe our
      findings in seven leukemic patients with fungal infections.

PMID- 9026928
TI  - [Rapid differential diagnosis of fetal blood versus maternal blood].

PMID- 9026929
TI  - [Use of the Sysmex NE1500 counter for the detection of hemoglobinopathies].

PMID- 9026930
TI  - [Allo- and autoantibody in a case of autoimmune hemolytic anemia associated with
      a myelodysplastic syndrome].

PMID- 9026931
TI  - [Autoimmune hemolytic anemia in common variable immunodeficiency].

PMID- 9026932
TI  - [Acute myeloid leukemia developing in the course of essential thrombocythemia].

PMID- 9026933
TI  - [Filling out the transfusion request form in a general hospital].

PMID- 9026934
TI  - [Thymogen in the treatment of type-1 diabetes mellitus].
AB  - Thymogen effect was assessed in patients with type 1 diabetes mellitus with
      clinical and laboratory evidence of secondary immunodeficiency. It was found that
      thymogen removes signs of secondary immunodeficiency due to activation of T
      lymphocyte differentiation. Clinical effect of thymogen was registered in 94.4%,
      laboratory effect in 83.3% of patients. The scheme of thymogen administration is
      suggested.

PMID- 9026935
TI  - [The effects of eiconol in elderly patients with non-insulin-dependent diabetes
      mellitus].
AB  - A nutritional additive eikonol containing polyunsaturated fatty acids omega-3 was
      given for a month (8 g/day) to correct vascular complications in 60 patients with
      non-insulin-dependent diabetes mellitus (NIDDM). Eikonol-treated NIDDM patients
      with diabetic retinopathy, polyneuropathy, angiopathy of the legs combining with
      arterial hypertension exhibited a reduction in the levels of total cholesterol,
      triglycerides, low and very low density lipoproteins cholesterol, a rise in
      concentrations of high density lipoproteins cholesterol. Blood pressure went
      down, peripheral vascular resistance and microhemocirculation improved. The
      findings evidence prophylactic and therapeutic efficacy of eikonol in vascular
      complications of NIDDM.

PMID- 9026936
TI  - [The thromboxane-synthesis inhibitor Ibustrin in the treatment of diabetic
      angiopathies].
AB  - 16 patients with insulin-dependent diabetes mellitus (IDDM) lasting 8-19 years
      had pronounced diabetic nephropathy (proteinuria stage), retinopathy (stage I, II
      or III), disturbed circulation in the lower limbs detected at foot
      dopplerography. For 3 months these patients received ibustrin (inhibitor of
      cyclooxigenase, blocker of tromboxane A2 synthesis and platelet aggregation)
      before renal function underwent positive changes: glomerular filtration rate
      increased in 13 patients (81%), 24-h proteinuria decreased in 12 patients (75%).
      Retinal vascular condition improved in 5 of 6 patients with nonproliferative
      retinopathy and in 2 of 5 patients with preproliferative retinopathy, in 1 and 3
      patients stabilization occurred, respectively. In proliferative retinopathy
      improvement and stabilization were registered in 1 and 3 of 5 patients,
      respectively. According to feet artery dopplerography the improvement, no changes
      and moderate aggravation occurred in 10(62%), 3(19%) and 3(19%) of patients,
      respectively The conclusion is made that ibustrin effectively inhibits
      progression of IDDM vascular complications, especially at early angiopathy
      stages.

PMID- 9026937
TI  - [Tumor-associated and acute-phase proteins in the diagnosis of cancerous
      exudative pleurisy].
AB  - The examination of 150 patients with pleural exudate of different origin (43
      cases of malignant and 107 cases of benign genesis) was made to elucidate
      diagnostic value of immunochemical serum and pleural fluid estimation of four
      tumor-associated proteins: carcinoembryonic antigen (CEA), beta 2-microglobulin
      (beta 2-MG), placental alkaline phosphatase (PAP), ferritin; three acute-phase
      proteins: C-reactive protein (CRP), lactoferrin, fibrin degradation products
      (FDP); expression of epithelial membrane antigen (EMA) in e date cells using
      monoclonal antibodies ICO-25. Determination CEA, beta 2-MG in the serum and
      pleural fluid, antituberculous an bodies in biological fluids proved
      diagnostically valuable for verification of pleural exudate characteristics. The
      discriminant analysis provided formulas for this differential diagnosis. The
      method identification in pleural fluid of cells expressing EMA with the use of
      monoclonal antibodies ICO-25 was found to be 2 times more efficient in detection
      of cancer cells than the standard light microscopy.

PMID- 9026938
TI  - [The prognostic significance of the beta 2-microglobulin level of the blood serum
      in multiple myeloma patients].
AB  - Pretreatment and treatment content of beta 2-microglobulin in blood serum was
      measured in 52 patients with multiple myeloma stage IIA, IIB, IIIA and IIIB. The
      above concentrations before treatment correlated with the disease stage, rose in
      the exacerbation, remained unchanged in stabilization, fell in effective therapy
      and returned to normal values in remission. However, in pronounced renal
      insufficiency (stage IIIB) the remission beta 2-microglobulin levels remained
      high. A 6 mg/l concentration proved critical for survival. The survival median at
      pretreatment beta 2-microglobulin content above 6 mg/l was 14 months, under 6
      mg/l--49 months. Routine estimation of beta 2-microglobulin levels is necessary
      for better control over multiple myeloma treatment, timely change of cytostatic
      drugs.

PMID- 9026939
TI  - [Photons and protons in radiation therapy. The prospects for developing a proton
      therapy based on a new Russian accelerator].
AB  - Body distribution of absorbed energy of ionizing radiation determines relations
      between the desired effect and associated radiation lesions. Common methods of
      photon radiotherapy are characterized by strong irradiation of healthy tissues.
      Accelerated protons enables an increase in gradient of doses between the
      radiation-exposed subject and adjacent tissues. It is thought valid to promote
      wider use of the new Russian proton accelerator for upgrading radiotherapy.

PMID- 9026940
TI  - [Quality-of-life support for patients during antitumor chemotherapy (a lecture)].

PMID- 9026941
TI  - [The optimization of the infusion therapy procedure in patients with acute
      leukemias].
AB  - In a trial of 202 patients with acute leukemia (AL) the authors studied the
      effect of volume and quality of infusion therapy (forced diuresis 2.5 l/m,
      parenteral nutrition, hemocomponent therapy) on early mortality, frequency of
      complications, complete remission, overall and relapse-free survival. It is shown
      that the response in remission induction depends on the scope and quality of
      infusion therapy. Balanced complete infusion therapy led to a complete remission
      in 75% and 92% of patients with acute nonlymphoblastic and acute lymphoblastic
      leukemia, respectively, compared to 29 and 50% for infusion-untreated patients.
      Early lethality was 6 and 0%, 42 and 18%, respectively. Higher efficacy of acute
      leukemia treatment in adjuvant balanced infusion therapy results from lower
      toxicity of chemotherapy and possible performance of induction therapy without
      reduction of drug doses.

PMID- 9026942
TI  - [The use of interferon-alfa (reaferon) in patients with chronic myeloleukemia].
AB  - Data on long-term interferon-alpha (reaferon) therapy in 6 patients with CML (5
      in chronic phase, 1 in acceleration phase) are presented. Clinicohematological
      remission was achieved in all the patients in a chronic phase irrespective of
      their group of risk. Cytogenetic improvement occurred only in one patient from a
      low-risk group. Reaferon had no effect in the patient in the acceleration phase.
      Tumor necrosis factor neither influenced viability of mononuclear bone marrow
      cells of patients before treatment nor suppressed proliferation. Dose independent
      reduction of cell viability was revealed in a patient in remission after reaferon
      therapy. There were no cases of apoptosis induction. Mechanisms of CML
      pathogenesis and interferon action in CML chronic phase are discussed.

PMID- 9026943
TI  - [The use of serpens for treating patients with benign prostatic hyperplasia].
AB  - 320 mg of serpense was given daily to 24 patients with benign prostatic
      hyperplasia (BPH) for 2 months. Control check-ups were performed each 30 days.
      The effect was judged by the patient's condition (I-PSS), quality of life,
      residual urine, the gland size, urodynamic picture and level of prostatic
      specific antigen (PSA). The response of BPH to serpense was noticeable,
      especially at the first stage of the disease (66.7%). Reduced serum PSA in
      serpense-treated patients may be explained by peripheral selective inhibition of
      5 alpha-reductase or, rather, by anti-inflammatory action of the drug.
      Antidropsical and antiinflammatory actions of serpense suggest its possible
      efficacy in chronic prostatitis.

PMID- 9026944
TI  - [The prevention of hemorrhagic cystitis during the performance of bone marrow and
      peripheral blood stem cell transplantation in the hematologic cancer clinic].
AB  - Investigators from Belarus Center for bone marrow transplantation examined the
      efficacy of preventing hemorrhagic cystitis induced by high-dose cyclophosphamide
      in preparation for hemopoiesis precursor transplantation in 22 patients with
      hematological diseases. The proposed preventive method implied administration of
      mesna (2-merkaptoetan-sulphonate) and alkaline forced diuresis. Its effectiveness
      was found high.

PMID- 9026945
TI  - [The treatment characteristics of non-insulin-dependent diabetes mellitus].

PMID- 9026946
TI  - [Thrombocytic disorders in pregnant women with chronic glomerulonephritis and
      hypertension].
AB  - To assess platelet changes in pregnant women with chronic glomerulonephritis
      (CGN) and essential hypertension (EH) we estimated platelet lactic dehydrogenase
      activity (LDH), beta-thromboglobulin and thromboxane B2 (TxB2) plasma levels and
      ADP-stimulated platelet aggregability. Five groups of gravidae (26-40 weeks of
      gestation) were studied: with EH (n = 20), with CGN and hypertension (n = 31),
      with CGN without hypertension (n = 29), with late toxemia (n = 11), nonpregnant
      CGN women (n = 10) and healthy pregnant women (n = 20). Activation of platelet
      function was found in gravidae with CGN and EH. Platelet disorders were
      especially pronounced in pregnant women with CGN and with EH, but they were less
      pronounced than in control group with late toxemia. We believe that hypertension
      is more important stimulating factor for platelet activation than renal disease.
      We suggest that platelet disorders in outpatients are brought about by
      endothelium damage caused by elevated blood pressure.

PMID- 9026947
TI  - [The treatment of pyelonephritis in pregnant women (a lecture)].

PMID- 9026948
TI  - [Chronic nonspecific lung diseases, pregnancy and labor].
AB  - External respiration and microcirculation were studied in 203 pregnant women with
      chronic nonspecific pulmonary diseases (CNPD). The uterus, placenta and fetus
      were subjected to echography in the course of pregnancy. Placental morphology was
      examined in 73 cases. The relationships existed between the course of pregnancy,
      delivery and severity, variant of CNPD, between characteristics of the
      complications and external respiration function, severity of obstructive
      syndrome, microcirculatory abnormalities. The results of microcirculation studies
      and placentography confirmed morphologically provided criteria of birth outcome
      prognosis, fetal and newborn condition.

PMID- 9026949
TI  - [The importance of including polyunsaturated fatty acids in the therapy of obese
      pregnant women to prevent late toxicosis and to decrease its incidence].
AB  - Lipid fatty acid composition and cholesterol levels in platelets, platelet
      aggregation were investigated in pregnant women with essential or alimentary
      constitutional obesity on combined therapy comprising polyunsaturated fatty acids
      versus those who were treated conventionally. The use of combined therapy allowed
      to increase the content of polyunsaturated fatty acids in total lipids, to
      achieve a 32% decrease in platelet cholesterol and a 19% decrease in platelet
      aggregation. The frequency of late gestosis reduced twice and of severe gestosis
      3 times in patients given polyunsaturated fatty acids.

PMID- 9026950
TI  - [Experience with using high doses of cerebrolysin in vascular dementia].
AB  - The efficacy and tolerability of high-dose neurotrophic drug cerebrolysin was
      studied in 20 patients with vascular dementia diagnosed by criteria NINDS-AIREN
      and DSM-IV. The drug was well tolerated, affected positively cognitive function,
      especially neurodynamic processes. EEG featured after treatment intensification
      of rapid rhythms power and a decrease in delta-activity spectrum. The highest
      effect of cerebrolysin was achieved in patients with mild cognitive defects.

PMID- 9026951
TI  - [The use of Ticlid in treating cerebrovascular diseases].

PMID- 9026952
TI  - [Depakine syrup in the treatment of therapy-resistant epilepsy].
AB  - Depakin syrup was given for several weeks in initial dose 300 mg/day with graded
      increase of the dose to 1200 mg/day to 11 patients aged 15-39 suffering from
      epilepsy and residual-organic affection of CNS with epileptic syndrome. A
      complete or partial discontinuation of the fits was achieved in 82% of the
      patients, primarily in those with partial and primary-generalized fits, partial
      fits with secondary generalization. It is concluded that depakin syrup treatment
      is justified in management of epilepsy, especially in the treatment-resistant
      cases.

PMID- 9026953
TI  - [Current problems in the diagnosis and treatment of acute exogenous poisonings].
AB  - Information, toxicometry and detoxication are most important problems of clinical
      toxicology today because exchange of information perfect the skill of
      toxicologist in diagnosis and choice of treatment, whereas measurement of the
      toxic factor, blood poison concentrations enables systemic computer analysis of
      critical conditions caused by poisonings. Treatment of acute poisoning produces
      the highest effect if detoxication method is used including blood detoxication by
      sorption-dialysis methods and intestinal lavage in combination with
      physiohemotherapy. This approach provides a rapid elimination of poison from the
      body and effective correction of homeostasis.

PMID- 9026954
TI  - [The drug therapy of chronic venous insufficiency (a trial of the clinical use of
      the preparation Detralex)].
AB  - 76 patients with severe venous insufficiency (CVI) entered the study. All the
      patients received 500 mg of Detralex twice daily for 2 months. The drug was well
      tolerated and relieved CVI symptoms in the majority of cases.

PMID- 9026955
TI  - [Contralateral compression--a new method for stimulating blood flow in the
      affected extremity of patients with chronic obliterative arteriopathies (a
      preliminary report)].
AB  - The authors have developed an original method of nonpharmacological correction of
      peripheral circulation (contralateral compression) based on intensive blood flow
      in the affected limb at the expense of limited blood flow in the contralateral
      limb. The method is simple, safe and effective and thus promising for wide
      clinical practice.

PMID- 9026956
TI  - [Problems in the use of intravenously administered immunoglobulin].

PMID- 9026957
TI  - [The standardization of the description of gun shells (bullets)].

PMID- 9026958
TI  - [The forensic medical evaluation of independent foot injuries and the
      establishment of expert versions of their origins].

PMID- 9026959
TI  - [The choice of the study method in forensic medical osteological identification].
AB  - Discusses the problems related to the theoretical validation of selecting a
      method of investigation, its application with due consideration for the algorithm
      of osteological identification, and assessment of the results of this or that
      method from the viewpoint of the objectiveness and informative value of the
      method for osteological identification.

PMID- 9026960
TI  - [The study of bone, nail and tooth fragments].

PMID- 9026961
TI  - [The detection of ABO system antigens in bone, nail and tooth fragments].
AB  - Fragments of the bones, nails, and teeth were examined in 12 forensic biological
      departments of bureaus for forensic medical expert evaluation of the Russian
      Federation. A total of 790 experiments were carried out with 145 bones, 5 teeth,
      and nails from 12 cadavers. In the overwhelming majority of cases the experiments
      were carried out with control investigations of blood, hair, salivary, and sweat
      samples. Modifications of the absorption-elution method were used to detect the
      AB0 antigens, these modifications involving all stages of the test (fixation, fat
      extraction, medium for elution, reagents, time factors in absorption and elution,
      etc.). Analysis of the data permitted the authors to make some conclusions and
      offer recommendations for practical biological experts.

PMID- 9026962
TI  - [The histopathology of ephedrone drug abuse].
AB  - Morphological changes of the viscera and skin were examined in the corpses of 8
      narcomaniacs who abused ephedrone, a narcotic prepared by ephedrine oxidation.
      Total systems angiopathies and vasculitides involving mainly the kidneys, heart,
      and brain were revealed. The mechanisms of the injurious effect of the narcotic
      are discussed.

PMID- 9026964
TI  - [Establishing the time of death by the constant of the reaction rate of spin
      label reduction].
AB  - The rate of the spin probe reduction by tongue homogenates was measured on
      postmortem days 15, 30, 45, 60, 75, 105, 135, 150, 165, 180, 195, 210, 225, and
      240 in order to evaluate the possibility of determining the time of death by this
      test. The constant of the rate of phenol probe reduction by tongue homogenates
      was used as the diagnostic sign of the time elapsed since death. The results
      indicate that using this parameter, the time of death may be determined within
      the period from 4 to 8 months postmortem.

PMID- 9026963
TI  - [The assessment of mental disturbances (mental illness) as a qualifying sign of
      the severity of bodily injuries].
AB  - Analyzes the problem of assessing the severity of bodily injury leading to mental
      disorders in the victim. Discusses a working classification of mental disorders
      resultant from various environmental factors (injuries), intended for forensic
      medical experts, psychiatrists, and physicians of other specialties. Offers a new
      methodological approach to forensic medical and psychiatric expert evaluation of
      such cases. Describes the typical examples from practical forensic medical and
      psychiatric expert evaluations.

PMID- 9026965
TI  - [The possibility for the carrying out of active deeds by the victim with the
      presence of foreign bodies in the brain].

PMID- 9026966
TI  - [The metrological assessment of the results of the quantitative determination of
      ethanol in biological fluids].
AB  - Presents reliable data on the metrological assessment of the results of measuring
      ethanol in human biological fluids. The results are recommended for practical
      forensic medical expert evaluations.

PMID- 9026967
TI  - [The extraction of organic compounds in model systems of liver tissue-aqueous
      solutions. 1. Changes in the pH of aqueous solutions in contact with liver
      tissue].
AB  - Analysis of the resultant mathematical models demonstrated that exposure of liver
      tissue to aqueous solutions of acids leads to an increase of pH, and its contact
      with alkaline solutions results in an appreciable decrease of the pH of the model
      system. This should be borne in mind when creating and analyzing analog models
      describing the process of extraction of various organic compounds from biological
      material.

PMID- 9026968
TI  - [The detection of tramadol and its metabolites in urine by chromatographic
      methods].
AB  - The authors recommend detecting a compound drug tramadol and its metabolites in
      urinary extracts by thin-layer, gas-chromatographic, high-pressure liquid, and
      other chromatographic methods. The metabolites were identified with due
      consideration for their fragmentation during an electron strike thereof and their
      trimethylsilyl derivatives, mobility during separation in a thin layer, and
      results of selective extraction at various pH. The proposed scheme of
      biotransformation includes the formation of products of O- and N- demethylation,
      N, N- and N,O-didemethylation and hydroxylation of the cyclohexane fragment. The
      Rf metabolite values and their mass spectra are presented. During gas
      chromatographic analysis at an evaporator temperature at least 250 degrees C
      tramadol undergoes thermal destruction with the formation of water molecules and
      cyclohexane structure.

PMID- 9026969
TI  - [The action of an explosion on the human body (the pathomorphological, forensic
      medical and criminalistics aspects)].

PMID- 9026970
TI  - [The retention of Baytan and Bayleton in cadaveric material].
AB  - Study of the preservation of baitan and baileton in cadaveric material revealed
      that baitan was partially transformed in baileton in cadaveric liver. The content
      of the studied compounds in cadaveric liver upon storage of different duration
      has been assessed.

PMID- 9026971
TI  - [The analysis of grandaksin in cadaveric material].
AB  - Grandaxine was measured in expert cadaveric material (gastric wall, small
      intestine, and kidney) by thin layer and liquid chromatography and UV
      spectroscopy. Chromatographic measurement in a thin layer of the adsorbent was
      carried out on L 5/40 M plates in the following solvent systems: tholuene-acetone
      25% ammonium hydroxide (50:50:1); ethyl acetate-methanol-25% ammonium hydroxide
      (17:2:1); chloroform-methanol (9:1); and chloroform-acetone (9:1). Analysis by
      high-pressure liquid chromatography was carried out by means of a Milichrome-4
      chromatographer with a UV detector on the column packed with Separone C18 (5 mcm)
      using a mobile phase acetonitrile-0.05 M disubstituted ammonium phosphate
      (55:45).

PMID- 9026972
TI  - [The determination of the group classification of sperm by the ABO system by
      means of the immunofluorescence reaction in a quantitative modification].
AB  - Differentiating lysis with proteinase K helps purify the preparations from stains
      on material evidences and thus permits the detection of more spermatozoa.
      Quantitative immunofluorescence and the Stat software helps objectively assess
      the results of the test by mathematical processing and more reliably detect this
      or that AB0 antigen in the spermatozoa.

PMID- 9026973
TI  - [A case of death from hemorrhoidal hemorrhaging].

PMID- 9026974
TI  - [An unusual method of suicide].

PMID- 9026975
TI  - [The characteristics and results of training at the Police Academy of the city of
      Sarasota, Florida (USA)].

PMID- 9026976
TI  - [The current status of personal identification by dental status].

PMID- 9026977
TI  - [Biomechanical criteria of the damaging action of an explosion].

PMID- 9026978
TI  - [The elderly poor and political slowness].

PMID- 9026979
TI  - [Gerontology: screening, prevention and age limits].

PMID- 9026980
TI  - [The elderly in TV commercials: ridiculous or respectable?].
AB  - This study on images of elderly (over 55 years old) in Dutch commercials involved
      a content-analysis of 1003 commercials. Older adults were shown in only 28
      commercials. Elderly persons, and especially older women, appeared to be highly
      underrepresented. Only a few commercials (i.e., health support products) are
      directed at older adults as a target-group. Elderly persons are mostly
      represented in roles that create a pleasant atmosphere, such as grandparent or a
      retired enjoyer of life. Besides, aging is used as a metaphor for quality and
      tradition. For men, aging involves authority and life-experience. Apart from
      these positive links with old age, commercials were found that present the
      elderly as physically weak or incompetent. A considerable amount of commercials
      were humoristic. The authors interpret the results as characteristic of a
      predominantly negative portrayal of the elderly.

PMID- 9026981
TI  - [Assessment of indications for admission to a nursing home: evaluation of the
      questionnaire indication Alkmaar].
AB  - This article aims at testing an assessment schedule which is generally applied in
      order to determine the necessity and urgency of admission into a home for the
      aged. The central question concerns the extent to which this schedule contributes
      to (1) objectivity, implying that applicants with similar 'needs' will have an
      equal opportunity of being admitted to the requested provision, and (2)
      efficiency, meaning that a clear distinction in the urgency of admission is being
      made according to the seriousness of 'needs'. The research therefore concentrates
      on two topics. First, the homogeneity and statistical reliability of the
      assessment schedule, i.e. the questionnaire which is used for measuring the need
      for (institutional) care. Second, the statistical association between the
      measured need and the urgency of admission into a home for the aged. The research
      rests upon data on 164 older adults who have requested for admission; this data
      were obtained by a local agency responsible for need-assessment in relation to
      institutional care. The findings are as follows: (1) the homogeneity of the
      instrument can be improved, (2) the reliability is fairly good, (3) the
      association between 'need' and 'urgency of admission' is not very strong,
      notwithstanding the fact that (4) persons with lower scores on ADL- and IADL
      capacities, with more psycho-social problems and with stronger feelings of
      anxiety have significantly better opportunities of being admitted to a
      residential facility. It is concluded that the association between 'need' and
      'urgency of admission' might be improved by refining the assessment schedule and
      standardizing its application.

PMID- 9026982
TI  - [Dementia and the Dutch Reading Tests for Adults].
AB  - The Dutch Adult Reading Test (DART) is a method to assess premorbid intelligence
      in brain damaged patients. This article describes a study in which subjects
      without dementia (n = 25), with mild dementia (n = 11) and moderate to severe
      dementia (n = 11) were tested with the DART. DART-scores of the no dementia and
      mild dementia groups did not differ, but were significantly lower in moderate to
      severe dementia. So, the DART appears to be sensitive to more severe cerebral
      pathology as occurs in more advanced dementia, but is very useful with patients
      with mild cognitive deterioration. For the first time the test-retest-reliability
      of the DART was determined: r = 0.87 to 0.98. Except in the severe dementia group
      the DART strongly correlates with educational level.

PMID- 9026983
TI  - [Acute intestinal obstruction in an elderly patient].
AB  - The correct diagnosis of an acute abdomen in the aged is difficult, because of
      its varying presentation. Intestinal obstruction as a cause of acute abdomen is
      five times more common in the elderly as compared to younger patients. Acute
      intestinal obstruction in elderly patients may be due to intestinal or
      gynaecologic malignancies, or more frequently to incancerated hernias, peritoneal
      adhesions or faecal impaction. This case report describes a 90-year old female
      patient with intestinal obstruction, due to a bilateral torsion of benign ovarian
      cysts. Urgent surgery was life-saving. This case demonstrates that early decision
      for adequate therapy can reduce morbidity and mortality, also in very old
      patients.

PMID- 9026984
TI  - [The cytomorphological characteristics of the epithelial layer of the gastric and
      duodenal mucosa in those who worked in the cleanup of the aftermath of the
      accident at the Chernobyl Atomic Electric Power Station].
AB  - The complex of cytomorphological changes (dystrophy, dysregeneration, dysplasia,
      metaplasia) and dysfunction of gastric and duodenal mucosa epithelium were found
      in 79 liquidators of the Chernobyl disaster. It was shown that the reparative
      capability of superficial epithelium was retained. The increased number of
      abnormal mitoses was observed. The highest proliferative activity of duodenal
      epithelium reflects the intensity of reparative processes in duodenum at acute
      phase of peptic ulcer disease.

PMID- 9026986
TI  - [The prenatal cytogenetic diagnosis of fetal chromosomal pathology in women in a
      high-risk group].
AB  - The results of investigation of 908 chorion and placental biopsy in 873 pregnant
      women of high risk a group is presented. Fetal pathology was diagnosed with the
      help of "direct" method and shot-term method of culture of chorionic villi and
      placenta, as well as method of long-term fetal lymphocyte cultures. The
      efficiency of invasive methods of prenatal diagnosis, and their role in decrease
      of perinatal disease and mortality was confirmed.

PMID- 9026985
TI  - [A comparison of the morphofunctional characteristics of the peripheral blood
      lymphocytes and the immune status of patients with malignant melanoma of the
      skin].
AB  - As a results of the study of immune status of 75 patients with malignant skin
      melanoma, some signs of immunodeficiency with failure of cell and humoral
      reactions were revealed. The degree of quantitative and qualitative changes of
      immune system depended on clinical-morphological features of malignancy
      development.

PMID- 9026987
TI  - [The age-dependent incidence of Down's syndrome and the free-radical theory].
AB  - Age-dependent distribution of Down syndrome frequency in the light of free
      radical theory of aging was carried out in this work. The frequency of Down
      syndrome had been analysed during the period of 1990-1995. The investigation of
      radical process intensity was performed in the group of women of child-bearing
      age by the chemoluminescence method. It has been demonstrated that the age of a
      woman is one of the main reasons both of Down syndrome frequency increase and
      free radical accumulation. The obtained analogy between age-dependent
      distribution of Down syndrome frequency and age-dependent accumulation of free
      radicals is one more argument for the role of free radicals in the pathogenesis
      of Down syndrome.

PMID- 9026988
TI  - [The incidence and clinical genealogical analysis of ovarian cancer in the
      Kharkiv region].
AB  - The analysis of oncoepidemiological state of ovarian cancer (OC) in Kharkov
      region in comparison with Ukraine within the periods before and after the
      Chernobyl NPP accident was conducted. Territorial differentiation of this
      pathology in the regions of Ukraine are represented. An increase in OC incidence
      among the women of Ukraine and Kharkov region was detected, especially increase
      of OC the south-east regions. Clinical genealogic analysis in the families of 102
      probands with OC, 60 women with benign ovarian cystomas and in 258 practically
      healthy women revealed malignant tumors of different locations. In probands with
      OC, the accumulation of this tumor, breast cancer and cancer of gastrointestinal
      tract was found. The necessity of clinical genealogic analysis of Ukrainian women
      was based.

PMID- 9026989
TI  - [A population genetics study of the allelic polymorphism in the hypervariable
      region of the apolipoprotein B gene in the population of different regions of
      Ukraine].
AB  - The allelic variation of the hypervariable locus from 3'-untranslated region of
      apolipoprotein B gene in healthy volunteers from different regions of Ukraine was
      analysed. Among 396 DNA samples studied, 13 allelic variants were identified with
      the number of repeats ranging from 29 to 53. The frequency of alleles varied from
      0.0013 to 0.3575 with the mean heterozygosity index 77.9%. The investigation of
      the genetic differences between 4 populations of different regions of Ukraine has
      been performed. A high level of the polymorphism and a heterozygosity index of
      APOB locus allow to recommend this polymorphic system as an informative marker
      for study of genetic structure population and to forensic medical analysis.

PMID- 9026990
TI  - [The characteristics of different types of mRNA expressed in the human brain].
AB  - Considerable decrease of expression of some "brain-specific" genes obtained in
      previous experiments was detected by means of differential hybridization of
      gridded human fetal brain cDNA library with total cDNA probes, synthetized on
      mRNAs isolated from the normal brain cells and several tumor cells. In contrast,
      for few genes expressed on low level in human fetal brain the evident increase of
      expression level in human brain tumour cells was found. The nucleotide sequences
      of some of these genes and previously isolated genes which have different
      specificity of expression were determined.

PMID- 9026991
TI  - [An analysis of the mutations in the gene of the mucoviscidosis transmembrane
      regulator protein (MTRP) in patients with congenital bilateral aplasia of the vas
      deferens].
AB  - The genetic background of congenital bilateral aplasia of vas deferens (CBAVD)
      was studied. Eight patients from Ukraine were enrolled in our study. In each
      case, the clinical diagnosis of CBAVD was confirmed by testicular biopsy. None of
      patients had other clinical features of CF except high level of sweet Cl.
      Individuals underwent genetic screening for mutations in CFTR gene. Genomic DNA
      from six individuals was analysed for the 9 mutations and from two patients for
      the 20 most common CF mutations in European population. In 3 patients, the
      mutation identified was delF508 and in 3 patients was found to have the R117H
      mutation (in all cases one mutation per individual only). Our results confirmed
      hypothesis that isolated CBAVD is incomplete (genital) form of cystic fibrosis.

PMID- 9026992
TI  - [The variability of the functional elements in the left domain of te control
      region in human mitochondrial DNA].
AB  - An analysis based on population data (approximately 600 individuals) of
      variability of functional elements (API-like element, termination-associated
      sequence TAS and direct repeats TAGTACATAAA) and non-functional hypervariable
      fragment of the left domain of the human mitochondrial DNA (mtDNA) control region
      is presented. It was shown that in the evolutionary respect these elements are
      relatively conservative structures. The possible role of these structures for the
      termination of 7S DNA synthesis in D-loop of the mtDNA as well as for the
      initiation of the replication of the human mitochondrial genome full-length
      chains is discussed. The lack of race-specificity in respect to functional
      elements of mtDNA is represented as evidence of absence of differentiation of
      human races for the organizations of the mitochondrial genome regulatory systems.

PMID- 9026993
TI  - [The complex assessment of the consequences of anthropogenic environmental
      pollution and the principles for their prevention].
AB  - Genetic monitoring on the basis of clinical-epidemiologic indices of congenital
      and hereditary pathology among newborns and spontaneous abortions as well as
      morphogenetic finding analysis in different age group representatives have been
      carried out. Mutation process dynamics in various ecological zone populations has
      been established. Dermatoglyphics and karyograme changes have been revealed their
      expressiveness depended on the general state of the organism, age and hereditary
      predisposition to polygenic diseases.

PMID- 9026994
TI  - [The distribution of histocompatibility antigens among donors (the city of
      Kiev)].
AB  - It was shown that the most frequent HLA antigens among Kiev residents are: in the
      locus A--antigen A2 (36.33%), A1 (25.0%), in the locus B--B8 (20.33%), B13
      (17.33%), in the locus C--CW4 (18.0%) and CW2 (12.33%). The frequency of B5
      antigen decreased from 26.67 to 11.67% and B12 antigen from 30.33 to 10.67% for
      the last 10 years. These data may be used as a control for to study the
      association of histocompatibility antigen system with the human pathology and for
      the formation of risk groups at some diseases.

PMID- 9026995
TI  - [The products of water chlorination as inducers of gene mutations].
AB  - Experimental data on water mutagenicity from Dnepro technological chain of pipe
      line water purification were obtained using Ames express method of gene mutation
      induction in histidine-dependent strains of Salmonella typhimurium series TA (TA
      98 and TA 100). It was shown that water mutagenicity depended on the level of
      water pollution by chemical substances in the river Dnieper and the use of
      chlorine for water disinfection.

PMID- 9026996
TI  - [The effect of thymogen on the chromosome aberration level in a culture of human
      peripheral blood lymphocytes].
AB  - The influence of thymogene on the frequency of spontaneous and formaldehyde
      induced chromosome aberrations in human peripheral blood lymphocytes was
      detected. High thymogene concentration (1000, 100, and 10 micrograms/ml)
      significantly decreased the proliferative activity of lymphocytes in culture. Low
      thymogene concentrations (1.0; 0.1; 0.01; and 0.001 microgram/ml) didn't decrease
      the mitotic activity of culture and hadn't mutagenic activity. Thymogene
      concentrations 1.0; 0.1; and 0.001 microgram/ml significantly decreased the
      frequency of formaldehyde-induced chromosome aberrations in lymphocytes. Possible
      mechanisms of gene protection by thymogene is discussed.

PMID- 9026997
TI  - [The prevalence and genetic heterogeneity of cleft lip and palate in the Lenkoran
      Astara area of the Azerbaijan Republic].
AB  - The data on labial and/or palatine cleft distribution and genetic heterogeneity
      in Azerbaijan Republic Lenkoran-Astara zone are represented. The average
      frequency of the given pathology is 1:1626 of newborns. We have observed the
      autosome-dominant as well as autosome-recessive forms of given pathology,
      associated with beta-thalassemia and Gopd enzyme deficiency.

PMID- 9026998
TI  - [The micronucleus test in human exfoliative cells as a method for studying the
      action of mutagens/carcinogens].
AB  - The data concerning the application of micronucleus assay in human exfoliated
      cells have been analyzed in the review. These data have shown that the study of
      micronuclei in human exfoliated cells is very promising, sensitive and rapid
      method for detection of action of mutagens/carcinogens as well as
      antimutagens/anticarcinogens on human organism in vivo.

PMID- 9026999
TI  - [An ultrastructural study of the hippocampal neurons in mice subjected to heat
      exposure].
AB  - The ultrastructure of hippocampal neurons in mice subjected to heat treatment for
      40 min at 42 degrees C was studied. Such a treatment has been shown to result in
      significant changes in the structure of pyramidal neurons. An increased chromatin
      condensation in the nuclei was found in addition to deep invagination of their
      envelopes and reduction or fragmentation of the reticulum cisterns. These changes
      were accompanied by mitochondrial swelling and increased number of clathrine
      vesicles around the Golgi complex. The heat exposure followed by feeding on
      vitamins and beta-carotin appeared to diminish chromatin condensation and kept
      the cisterns invariable.

PMID- 9027000
TI  - [The ultrastructural heterogeneity of the pulmonary phagocytes in acute and
      chronic inflammation].
AB  - Summarized are data on cytologic and ultrastructural characteristics of lung
      phagocytes obtained from bronchoalveolar lavage in patients with inflammatory
      lung diseases of different genesis. Autoradiographic studies in vitro,
      supplementing data of structural analysis, enabled us to get the information on
      metabolic and proliferative activity of alveolar macrophages.

PMID- 9027002
TI  - [The identification of synapses in the cerebral cortex].
AB  - The correlation between structure and function of synapses is discussed.
      Identification of 4 types of synapses has been made based on the authors' own
      evidence provided for the rat sensomotor cortex with the light and electron
      microscopy: 1--asymmetrical (excitatory, glutamate- or aspartatergic); 2-
      symmetrical (inhibitory, GABAergic); 3--symmetrical (disinhibitory, GABAergic); 4
      -symmetrical or asymmetrical (modulatory, monoaminergic). The ultrastructure of
      some synaptic categories may be equalized with their function. It makes possible
      to identify not only excitatory and inhibitory synapses, as considered before,
      but also disinhibitory and modulatory ones.

PMID- 9027001
TI  - [A comparative study of the nonhistone chromosomal proteins (pp23) from rat and
      bull kidneys].
AB  - The bovine nonhistone protein pp23 differs from that of rat origin both
      immunologically (precipitation, specific interaction with monoclonal antibodies
      to rat pp23) and functionally (capability to stimulate expression of hetero
      organic antigens on the membrane of intact hepatocytes cultured in suspension).
      These differences, however, are not recognized in the experiments on stimulation
      of DNA synthesis in Swiss 3T3 cell resting culture, when a more general cell
      function (proliferation) is dealt with, rather than a narrow specific one, such
      as synthesis of tumor-associated hetero-organic antigen of kidney origin.

PMID- 9027003
TI  - [The effect of isoproterenol on protein extrusion from tissue explants of the
      mouse mamma].
AB  - Culture of mouse mammary gland cells was treated with beta-agonist isoproterenol
      to result in dose dependent increase in protein. Propranolol, beta-antagonist,
      blocked this effect of isoproterenol. According to electron microscopic analysis,
      application of isoproterenol leads to disappearance of vesicles from apical zones
      of the secretory cells, and to increase in casein micelles in alveolar lumen. As
      follows from the obtained data, catecholamines play part in regulation of mammary
      gland activity, stimulating process (via beta-adrenoreceptors) of protein
      extraction from secretory cells of the mouse mammary gland.

PMID- 9027004
TI  - [The nuclease activity of the cell nuclei in 2 lines of murine myeloma sp2/0
      differing in their resistance to cytostatics in adriamycin-induced apoptosis].
AB  - The endonuclease activity of two drug-sensitive and drug-resistant mouse myeloma
      cell lines during cytotoxic drug-induced apoptosis was studied. It was shown that
      internucleosomal fragmentation of DNA in drug-sensitive line sp2/0, undergoing
      apoptosis in the presence of adriamycin and colchicine, was not dependent on
      intracellular calcium content and was associated with activation of both Ca(2+)
      Mg(2+)-dependent and acidic cation-independent endonucleases. In contrast, in
      multidrug resistant spEBR-5 cells, treated with the same drugs, only Ca(2+)
      Mg(2+)-dependent endonuclease activity was detected. These data suggest that the
      differences in the pattern of endonuclease activity revealed in these cells are
      linked to drug-resistant phenotype and do not depend on the apoptosis-inducing
      agent used.

PMID- 9027005
TI  - [The growth-stimulating and immunomodulating activity of culture media
      conditioned by transformed fibroblasts from serum-free lines].
AB  - Five cell lines of transformed rodent fibroblasts capable of unlimited growth
      without exogenous proteins were studied. It has been demonstrated that the media
      conditioned by these cells (CMs), the protein preparations obtained from CMs, or
      the feeder cell cultures of the serum-free cell lines are mitogenic to mouse
      hybridoma cells as well as to primary cell cultures of the rat bone marrow. The
      addition of CMs proteins into mixtures of mouse splenocytes and transformed
      target cells resulted in stimulation or suppression of the splenocyte
      cytotoxicity when YAC-1 [correction of JAC-1] or K562 cell targets were used. A
      18-20 h splenocyte preincubation with proteins, released by transformed rat
      fibroblasts of the serum-free cell line LRec-1sf, resulted in a 1.5-4-fold
      increase in K562 cell lysis by murine natural killer cells. By contrast, the
      target cell preincubation with the same proteins resulted in a 1.5-2-fold
      decrease in K562 cell sensitivity to cytotoxic effect of natural killer cells.
      Taken together our data show that the transformed rodent fibroblasts, growing
      without exogenous proteins, produce and release into the culture medium some
      growth stimulating, immunomodulating and immunoprotective factors.

PMID- 9027006
TI  - [The cytogenetic study of established Syrian hamster cell lines. I. A comparative
      analysis of the karyotypes of the BHK-21 (C-13) sublines].
AB  - Karyotypes of eight BHK-21 (C-13) cell sublines, obtained from a variety of
      sources and available in the cell culture collection of our Institute, have been
      studied using G- and C-banding, and silver staining of chromosomes. These
      sublines with similar modal numbers of chromosomes (40-44) are found to vary
      essentially in composition of both normal chromosomes and markers. In spite of
      the fact that many markers are constant in several cell sublines, it was
      impossible to determine the marker chromosomes typical of BHK-21 (C-13) cell by
      analogy with those typical of HeLa cells. Our studies have shown that BHK-21 (C
      13) cells exhibit nonrandom chromosomal alteration involving heterochromatic
      regions, particularly long arms of X- and Y-chromosomes and centromeric regions
      of 1, 3, 6 and X-chromosomes. Deletions of Xq, Yq and heterochromatic short arms
      of autosomes have also been observed. The markers more commonly consist of the
      material of chromosomes 1, 2, 3, 4, 5, 8, 9, 16, 17, 18, 19, X and Y.

PMID- 9027007
TI  - [The cytogenetic study of established Syrian hamster cell lines. II. A
      comparative analysis of the karyotypes of cell lines HaK, CER and BHK-21 (C-13)].
AB  - A comparative cytogenetic investigation of the Syrian hamster HaK, CER cell lines
      and BHK-21 (C-13) sublines was undertaken using G- and C-banding, and silver
      staining of chromosomes. BHK-21 (C-13) cell sublines were found to have diploid
      associated chromosome sets, whereas HaK and CER cell lines are characterized with
      triploid and tetraploid associated chromosome sets, resp. In sum, in all the
      analysed cell lines 100 marker chromosomes were identified, with 85 ones having
      unique morphology. The finding indicates a nonaccidental appearance of lesions
      for normal chromosomes in forming markers. Another arrangement of "hot break
      points" on chromosomes is more typical of HaK and CER cell lines, than of BHK-21
      (C-13) sublines. The localization of "hot break-points" on chromosomes in BHK-21
      (C-13) sublines is specific of the Syrian hamster cells transformed with
      oncogenic viruses.

PMID- 9027008
TI  - [The cytogenetic study of established Syrian hamster cell lines. III. An analysis
      of the NOR-marker chromosomes in Syrian hamster cell cultures by using
      differential chromosome Ag-->G restaining].
AB  - Using silver staining --> G-banding restaining procedure it was found that the
      Syrian hamster chromosomes had nucleolar organizers on subtelocentric chromosomes
      2, 6, 9, 10 and 13, and on acrocentric chromosomes 16, 17 and 19. In this case,
      NORs may be recognized only on one of homologous chromosomes, and no more than 9
      NO-chromosomes may be found in one metaphase plate. In HaK, BHK-21 (C-13) BKK and
      BHK-21 (C-13) C cell lines, chromosomes 6, 9, 16, 17 and 19 have NORs, and in
      each line there are specific marker chromosomes with NOR. The markers consist of
      the material of chromosomes 6, 9, 16 and 17, with only chromosomes 16 and 17
      being incorporated into rearrangements by their NORs. The silver staining --> G
      banding restaining procedure makes possible not only identification of NO
      chromosomes, but also refinement of the marker origins.

PMID- 9027009
TI  - [The effect of coccidia of the genus Sarcocystis on the morphofunctional
      organization of the skeletal musculature in experimentally infected mice. I. The
      muscle fiber].
AB  - At the ultrastructural level, the cellular response of skeletal muscles on
      developing Sarcocystis muris sarcocysts has been followed in mice at different
      times after sporocyst feeding, i.e. in 1, 2.5, 6 and 10 months, resp. The
      developing cyst creates a progressive degeneration of the infected muscle cell
      that involves organelle disorganization and formation of numerous vacuoles in the
      cytoplasm as a consequence of cell edema. Products of the host cell degradation,
      shaped as fibrillar-granular structures, are seen to find their way to the cyst
      wall outgrowings, where they become denser and on being covered with membranes
      appear eventually in the sarcocyst ground substance. Later on, the membranes
      around the granules disappear. In the course of its development, the sarcocyst
      totally destroys not only the harbouring muscle cell and the nearest connective
      tissue elements of the endomysium, but also the previously intact neighbouring
      cells. The involvement of some proteolytic enzymes in this process is suggested.

PMID- 9027010
TI  - [The effect of coccidia of the genus Sarcocystis on the morphofunctional
      organization of the skeletal musculature in experimentally infected mice. II. The
      connective tissue elements of the endomysium].
AB  - As an extension of the previous communication (Radchenko, et al., 1996), a study
      was made of the response of connective tissue elements, surrounding the
      Sarcocystis muris infected muscle fibers. As earlier, the S. muris sarcocysts
      were examined in mice 1, 2.5, 6, and 10 months after sporocyst feeding. Within
      the first 2.5 months after infection, marked accumulations of lymphocyte-like
      cells and collagen fibres are observed in the endomysium, and simultaneously the
      activity of capillary endothelial cells is seen to enhance due to the appearance
      of much more micropinocytotic vesicles, compared to the uninfected control. All
      this may be qualified as the host organism protective reaction to the parasitic
      infection. 6 and 10 months after infection, not only collagen fibres, but also
      some other fibrillar structures of the endomysium undergo degradation, the damage
      of capillary endothelial cells starting from breaking the outer membrane (in 6
      months) and terminating in lysing the whole cell (in 10 months). Besides,
      structural abnormalities were noticed in the axon endings.

PMID- 9027011
TI  - [A comparison of the amount of DNA in the sporoplasm nuclei of the myxosporidian
      and actinosporidian phases of the life cycle of the parasitic protozoan
      Zschokkella nova--a representative of the Myxozoa type].
AB  - Average DNA amounts in sporoplasm nuclei of the actinosporean and myxosporean
      developmental phases of Z. nova were compared. The average DNA amount per one,
      presumably diploid, sporoplasm nucleus of the actinosporean phase spores was
      twice as large as the average summarized DNA amount in two, presumably haploid,
      nuclei of the myxospsorean phase spores of Z. nova. It is suggested that
      sporoplasm nuclei in the actinosporean phase spores of Z. nova are diploid
      postsynthetic, whereas sporoplasm nuclei of the myxosporean phase spores are
      haploid. The data do not contradict the earlier supposition (Uspenskaya, 1955a,
      1955b), that the investigated spores may be developmental stages of the same
      organism. The data support the idea of haploidy of the myxosporean phase spores
      (Uspenskaya, 1984) and diploidy of the actinosporean phase spores (Marques, 1984)
      in Myxozoa.

PMID- 9027012
TI  - [The patterns of the karyotypic evolution of cells in culture].
AB  - Numerous personal and literary data on the karyotypic variation of cell lines
      during their establishing and long-term culturing have been reviewed. A new
      notion about karyotypic evolutionary pathways of cells in culture is presented. A
      detailed original approach to cytogenetic study of permanent cell lines is given,
      which allows, via karyotype reconstruction, to obtain finally a new karyotypic
      characteristics-the generalized reconstructed karyotype (GRK). Application of the
      cytogenetic approach as a criterion for the control of authenticity, purity and
      stability of cell lines is discussed. The cell line analysis by means of GRK
      elicited that the cell line evolution in vitro passes through two stages: a stage
      of establishment, and a stage of stabilization, both differing in karyotypic
      variability of cell populations and clonal selection in culture. The data
      indicate that it is important in experiments to utilize cell lines being in the
      stage of stabilization and to characterize chromosomally the cell line at the
      same passage when it is used. Above all, a comparison of karyotypic variations of
      tumor and leukemic cells in vitro and in vivo has revealed their common
      karyotypic evolution regularities (a nonrandom character of numerical and
      structural chromosome changes and the loss of one of the sex chromosomes) and the
      karyotypic evolutionary regularities characteristic solely of cells in culture.
      The main of these being a balanced chromosome set in the cell population as a
      whole and obligatory retention of diploidy in all chromosomes of the normal set
      by the majority of human and animal cell lines. It has been revealed that no less
      than two homologs of each autosome are present in cells of at least 85% of
      examined lines. Other cell lines (at least 15%) of a generally neurogenic origin
      are shown to be notable by keeping partial or complete monosomies on autosomes
      throughout the long-term culturing. Peculiarities of the karyotypic evolution of
      the latter are regarded in detail in addition to the data on the expression of
      oncogenes and other growth-associated genes in their cells. It is suggested that
      there are three main compensatory mechanisms through which cell lines with
      autosomal monosomies may maintain the vitality in culture: polyploidization of
      initial cell clones, oncogene amplification, mainly of the myc-family oncogenes,
      and fragmentary or complete extracopying of several autosomes. In summary,
      perspective of cell line cytogenetics as a field of biology of the cell in
      culture is discussed.

PMID- 9027013
TI  - [Structural changes in the cytoskeletal actin in cultured muscle cells when the
      cultures are stimulated by polystyrene latex].
AB  - As we reported elsewhere, the addition of polysterol latex (180 nm) to chick
      muscle culture accelerated several myogenesis stages, such as proliferation and
      fusion. In the present work we tried to determine the role of cytoskeletal actin
      in the mechanism of acceleration. The localization of cytoskeletal actin was
      studied in normal and latex induced cultures with the help of rodamine-
      phalloidin. The obtained data have shown that latex beads added to the cultural
      medium brought about acceleration of cell spreading (the number of spread cell
      was approximately five times more in comparison with the norm) and enhanced the
      development of actin network (90% of the cell area was filled with stress-fibrils
      in 20 h, instead of within 1-3 in the norm). It is proposed that muscle cells
      interact primarily with latex beads in the cultural medium before seeding on the
      glass. From this point of view latex beads can be considered as a primary
      substratum. The cell contact with the primary substratum initiates the actin
      network reorganization that leads to activation of cell spreading with a
      subsequent acceleration of myogenesis process: adhesion, proliferation and
      fusion.

PMID- 9027014
TI  - [A cytophotometric study of the amount of DNA in the macro- and micronuclei of
      the infusorian Nyctotherus cordiformis from the gut of tadpoles and juveniles of
      the common frog].
AB  - The investigations of DNA amounts in the nuclei of the ciliate Nyctotherus
      cordiformis was continued. The measured ciliates were collected from guts of
      tadpoles and the most small frogs just from the water. The DNA content was
      measured (in arbitrary units--a.u.) in the nuclei of cysts, precysts, vegetative
      ciliates and small frogs. This paper is the second part of the investigation. The
      first part dealt with DNA amounts of the nuclei of the vegetative ciliates tested
      in spring, autumn and winter. The amount of the Feulgen-DNA complex was measured
      with a two-wave microcytophotometer MCFU-1. The average content of the DNA ranged
      from 1.7 +/- 2 a.u. in the Mi of cysts to 2.6 +/- 0.1 a.u. in the Mi of the
      youngest frogs. The DNA content of the Ma ranged from 275 +/- 21 a.u. in cysts to
      479 +/- 25 a.u. in vegetative ciliates. The DNA content in presynthetic Mi (G1)
      is supposed to be approximately 1.3 and approximately 2.6 a.u. in postsynthetic
      (G2) Mi. Using nuclei of erythrocytes of Rana temporaria as internal standard,
      the DNA content of a 2 c Mi from tadpoles of N. cordiformis is supposed to amount
      to 0.57 pg or approximately 350 gDa. The DNA amount in Ma of N. cordiformis is at
      average 140-220 times as that of Mi.

PMID- 9027015
TI  - [The association of a protein regulator of intracellular Rab7 membrane transport
      with endosomes containing an epidermal growth factor receptor with activated and
      inactivated tyrosine kinase].
AB  - By double indirect immunofluorescent microscopy, Rab7, traditionally considered
      as a late endosomal marker, has been demonstrated to colocalize with an
      internalized epidermal growth factor receptor (EGFR) possessing active and
      inactive tyrosine kinase (TK). The epidermal growth factor (EGF), which induces
      TK activity of EGFR, and monoclonal antibody Mab 108, which does not, have been
      exploited as ligands to stimulate endocytosis of EGFR. Colocalization between
      EGFR and Rab7 has been detected at both early (10 min) and delayed (60 and 120
      min) endocytosis of EGFR, while it turned out to be much more obvious at the
      later ones. A comparison between EGFR-mediated and peroxidase fluid-phase
      endocytoses has revealed that Rab7 failed to be recruited on endosomal
      structures, containing peroxidase, even after 180 min endocytosis. Subcellular
      fractionation of endosomes containing 125I-EGF and 125I-Mab 108 in Percoll
      density gradients, in parallel with the analysis of ligand degradation, have
      verified the efficient transition of EGF-receptor complexes into the late
      endosomes and retention of Mab 108-receptor complexes within the early (sorting)
      endosomes. Taken together, the data cotained suggest that endogenous Rab7 is able
      to be recruited not only on late but also on maturating sorting EGFR-containing
      endosomes, thus mediating sorting along the EGFR endocytotic pathway.

PMID- 9027016
TI  - [The determination of the complementation groups for the cells of patients with
      xeroderma pigmentosum and the Cockayne syndrome found in Russia].
AB  - Complementation groups for xeroderma pigmentosum (XP) and Cockayne's syndrome
      (CS) cells have been first determined for patients encountered in the former
      Soviet Union. The determination was carried out using fusion of fibroblasts to be
      examined with those of already known complementation groups, and subsequently
      registering the level of DNA unscheduled synthesis (for XP cells) and RNA
      synthesis recovery (for CS cells) after UV-irradiation. The evidence of the
      complementation was normalization of these indexes. Cells of XP2SP and XP4SP
      patients are shown to fall under the XPC complementation group, whereas CS1SP
      cells are classified within the CSA complementation group.

PMID- 9027017
TI  - [Revision: guiding principles for successful or unsuccessful stabilization of
      subtrochanteric femoral neck fractures. A review].
AB  - Over a long period of time the dislocated and unstable fracture of the femoral
      neck has been called "the unsolved fracture". Regardless of all technical
      improvement developed the head- and joint preserving treatment of this fracture
      seemed to remain an "unsolvable" problem. Fundamental reason for this
      discrediting judgement was the continuously high rate of complications like
      segmental collapse of the femoral head and pseudarthrosis of the femoral neck.
      The invention and speedy acceptance of hip joint replacement made many surgeons
      hope that the "unsolved" problems of treating femoral neck fractures could be
      guided to a definite conclusion. This revising discussion is done to bring home
      being familiar with the experience gained by practising the head- and joint
      preserving surgery of femoral fractures.

PMID- 9027018
TI  - [Heparin-induced thrombocytopenia Type II (HIT II) A fatal complication of
      heparin use for thromboembolism prevention].
AB  - Heparin-induced thrombocytopenia type II (HIT II) is the most severe complication
      during prophylactic treatment with low doses of heparin. Five cases demonstrate
      the life-threatening consequences of this immune-mediated thromboembolic disease.
      In order to improve prognosis it is most important to start therapy just before
      diagnosis is assured by laboratory tests. First choice treatment is the low
      molecular-weight heparinoid Orgaran. In patients with an episode of HIT II both
      low-molecular-weight heparin and unfractionated heparin will be contraindicated
      for a life time.

PMID- 9027019
TI  - [Radiation burden to the hands of surgeons in intramedullary nailing].
AB  - During 41 procedures of intramedullary nailing of femoral and tibial fractures
      the primary surgeon and the first assistant wore ring dosimeters on their
      dominant index fingers. While the average fluoroscopy time per procedure was 4.6
      min the average dose of radiation to the dominant hand of the primary surgeon was
      1.27 mSv and 1.19 mSv to the first assistant. The dose limit for the extremities
      is 500 mSv per year recommended by the International Commission on Radiological
      Protection. Extrapolation of the average dose of the primary surgeon and first
      assistant per procedure of 1.23 mSv leads to the result, that the recommended
      dose limit of 500 mSv would only be exceeded if more than 407 intramedullary
      nailing procedures are carried out per year. The duration of fluoroscopy-time
      correlated with the radiation dose of the hands of the surgeons, though it was
      determined by phantom measurements that the majority of radiation exposure
      occurred during brief exposures of the hands in the direct X-ray beam on the X
      ray tube near side of the patient.

PMID- 9027020
TI  - [Revision surgery of knee endoprosthesis].
AB  - Thirty-one revisions for aseptic or septic loosening of knee arthroplasty have
      been performed between 1983 and 1995. In 18 cases we had loosening of uni- or
      bicondylar prosthesis and in 13 cases a tricompartmental revision arthroplasty.
      With an average of 53 months (1.5 to 13 years) after the last operation 21
      patients could be examined. Main reasons for failure of uni- and bicondylar
      prosthesis were as well a proceeding of the arthritis in other compartments,
      instability, incorrect alignment and other reasons depending on the surgical
      technique. We found similar reasons in aseptic loosening of total knee
      arthroplasties including wrong choice of non-constrained condylar prosthesis.
      Seven cases of late infection affected semi-constrained prosthesis. Two of the
      reimplantations in a 2-stage procedure failed. Using the Insall-Score in the
      follow-up the patients reached 71.9 points in the knee score and 58.9 points in
      the functional score. Patients with former aseptic loosening reached better
      results than these with septic loosening. 38% were absolutely painfree, 14%
      complained about permanent pain. Unlimited walking was found 5 times, none of the
      examined persons was unable to walk. Main problems in revision surgery concern
      reconstruction of a good alignment and the management of bone loss.

PMID- 9027021
TI  - [Autologous keratinocyte culture on hyaluronic acid ester membranes: an
      alternative in complicated wound management?].
AB  - Cultivation and transplantation of autologous keratinocytes has been used in the
      last 15 years to treat complicated wounds of different origin. In spite of
      excellent technical advancements and clinical experiences cultured keratinocyte
      grafting still is associated with practical limitations. Application of
      hyaluronic acid ester membranes as carrier substrate for the transfer of
      keratinocytes allows improved graft handling: reduces total time required for
      tissue cultivation and furthermore enhances vitality of the keratinocytes because
      of possible grafting at semiconfluence.

PMID- 9027022
TI  - [Quality assurance in trauma surgery--meaning, characteristics and methods].
AB  - For trauma surgeons the compliance with and keeping to well organized and planned
      courses of action is obligatory. This is valid as well for the highly sensitive
      areas of preclinical emergency treatment, the primary treatment in the hospital
      and the exceptional management in polytrauma, as for treatment of solitary
      injuries of the musculo-skeletal system. Despite considerable activities--so far
      voluntarily--(optimization of courses of action, classification systems for
      injury grades, algorithms and close-meshed further education) control mechanisms
      are demanded by politicians and insurance companies. Therefore, comprehensive
      quality control is strived for in all different types of insurance coverage
      systems. In spite of justifiable restraints against control mechanisms, which
      oppose increasingly medical freedom in diagnostics and treatment, only
      cooperation with and proficient guidance of the often self-appointed quality
      assurance personnel is useful.

PMID- 9027023
TI  - [Committee "Hospital Hygiene and Infection Prevention" of the Robert-Koch
      institutes not authorized by a vote of the scientific organization].

PMID- 9027024
TI  - [Is the NIDEP-Study suitable in the assessment and appraisal of nosocomial
      infections in Germany?].

PMID- 9027025
TI  - [The possibilities for the prognostic assessment of toxic-septic shock in
      peritonitis].

PMID- 9027026
TI  - [A giant neurinoma of the stomach].

PMID- 9027027
TI  - [A method for probing the common bile duct].

PMID- 9027028
TI  - [Reconstructive-restorative operations on the hand in the polyclinic].

PMID- 9027030
TI  - [The first Moscow International Congress of Surgeons (7-10 August 1995, Moscow)].

PMID- 9027029
TI  - [Epidural electrostimulation of the spinal cord in obliterating diseases of the
      peripheral arteries].
AB  - Under study was the efficiency of epidural electrical stimulation of the spinal
      cord (ESSC) of 237 patients with obliterating diseases of the peripheral
      arteries. Reconstructive operations proved to be impossible in all the patients,
      and conservative treatment was not successful. The clinical status of 169
      patients was determined as the 3rd stage, in 68 patients as the 4th stage after
      Fontain. The period of observation was 35.6 months at an average. High amputation
      was performed in 64 patients in spite of ESSC. In the other cases when the
      extremity could be kept safe, the intensity of pain was considerably relieved
      (more than 75%). We believe that ESSC can considerably relieve the intensity of
      the pain syndrome and improve the quality of life in patients with critical
      ischemia of the extremities when traditional methods of treatment are not
      possible.

PMID- 9027031
TI  - [Is vagotomy necessary in perforating ulcers?].

PMID- 9027032
TI  - [The therapeutic procedure in wounds of the heart].

PMID- 9027033
TI  - [The use of intravascular laser irradiation of the blood in surgery].

PMID- 9027034
TI  - [The choice of the type of vagotomy in the planned surgery of peptic ulcer].
AB  - An analysis of 175 organ preserving operations for duodenal ulcer is presented.
      Lethality was 1.24%; intraoperative complications--2.48%; postoperative
      complications--6.83%. Long-term results were followed in 61.5% of the patients.
      They are analyzed according to the kind of vagotomy and draining operations used.
      The author recommends to use drainage of the stomach more often, combined
      vagotomy should be chosen as the kind of vagotomy.

PMID- 9027035
TI  - [The ultrasonic diagnosis of tumorous diseases of the stomach and intestines].

PMID- 9027036
TI  - [The first human blood transfusion in Russia taking isohemagglutination factors
      into account].

PMID- 9027037
TI  - [Professor Vsevolod Ivanovich Korkhov (on the centenary of his birth)].

PMID- 9027038
TI  - [Intragastric proteolysis after selective proximal vagotomy].

PMID- 9027039
TI  - [The clinical picture and treatment results in duodenal ulcers with a hereditary
      predisposition].
AB  - The literature data and results of personal investigations are presented which
      concern the analysis of the clinical picture and results of treatment of
      hereditary duodenal ulcers. Under examination there were 245 patients with
      duodenal ulcers. Hereditary aggravation was established in 81 of the patients.
      The results of examinations of this group of patients were compared with those
      obtained when examining 38 patients having the ulcer disease of not hereditary
      nature. It was stated that hereditary duodenal ulcers have specific clinical
      picture which must be taken into consideration in surgical treatment of the
      disease.

PMID- 9027040
TI  - [The motor-evacuatory and acid-producing functions of the stomach in patients
      with complicated peptic ulcer combined with thyrotoxicosis].

PMID- 9027041
TI  - [The surgical treatment of polyps and early forms of cancer of the large
      intestine].
AB  - The article describes the present-day principles of surgical treatment of polyps
      and early forms of colorectal carcinoma appearing against their background. The
      investigation performed has shown that all benign adenomas of the colon can be
      successfully treated by local dissection. Sessile tumors located on the lower-
      and middle-ampullar portions of the rectum, are liable to endorectal dissection,
      in pedicular tumors endoscopic polypectomy is most expedient. In cases with
      carcinoma against the background of adenoma, the main criterion determining
      choice of the method of surgical intervention is the degree of ingrowth of the
      tumor into the colon walls. An analysis of long-term results of treatment shows
      that in carcinoma of the colon developing against the background of adenoma,
      local dissection is not inferior in efficiency to typical radical operations.

PMID- 9027042
TI  - [The prognostic significance of the level of the blood antiproteinase potential
      in peritonitis].
AB  - It was shown that the level of proteinase alpha 1-inhibitor (alpha 1-i.p.) in the
      toxic phase of peritonitis was reduced. In transition of the toxic phase to the
      terminal one the level of alpha 1-i.p. increases which suggests the preserved
      function of the liver. The terminal phase proper is accompanied by a considerably
      decreased level of the inhibitor. For this phase proteinase inhibitors should be
      administered. The level of activity of alpha 1-i.p. can serve as a prognostic
      criterion of the peritonitis course.

PMID- 9027043
TI  - [A comparison of the results of the surgical and the conservative corrections of
      hyperlipidemia in treating atherosclerosis].
AB  - Long-term results of surgical correction of hyperlipidemia in 46 patients with
      obliterating atherosclerosis of lower extremities were compared with results of
      conservative treatment of 41 patients with the same pathology within the terms
      from 6 months till 5 years. It was shown that the surgical correction of
      hyperlipidemia resulted in more considerable and stable decrease of the blood
      lipid level as compared with the conservative treatment, in better course of the
      concomitant IHD and arterial hypertension.

PMID- 9027044
TI  - [Patterns in the spread of the vertical blood reflux in the musculo-venous "pump"
      of the foot in varicose disease].
AB  - An analysis of the complex clinical and phlebographic examination of 84 patients
      with the varicose disease was made. Eight variants of the state of the valve
      apparatus of profound veins of the foot were established. Main regular features
      of spread of the retrograde blood flow the profound veins along insufficient
      perforating to the superficial veins were determined. A classification of
      incompetence of the valve apparatus of the profound veins of the foot was
      developed which allows the choice of surgical procedures depending on the injury
      degree.

PMID- 9027045
TI  - [The biomechanical characteristics of the hip joint during endoprosthesis].
AB  - Under consideration was the interaction of the hip joint endoprosthesis pedicle
      with the femur. Causes of shaking the prosthesis pedicle, fracture of the femur,
      progressing deforming arthrosis were analyzed. Formulas for calculating the
      character of interactions of the prosthesis pedicle with the femur are presented,
      as well as risk factors and recommendations for practical use. The article is
      illustrated with a clinical case.

PMID- 9027046
TI  - [Leiomyomas and leiomyosarcomas of the stomach].

PMID- 9027047
TI  - [Mechanical obstructive ileus of the small intestine due to simultaneous
      fibrolipoma and invagination of the small intestine].

PMID- 9027048
TI  - [A rare complication of leiomyoma of the colon].

PMID- 9027049
TI  - [Lipoma of the large intestine].

PMID- 9027051
TI  - [The immunological and biochemical reactions of the cerebrospinal fluid in
      victims of blast injuries of the skull and brain].
AB  - An analysis of immunobiochemical indices of the cerebrospinal fluid has shown
      possibilities to establish objective mechanisms of injuries of the brain by
      explosions. Biochemical manifestations of the cytolysis syndrome can be taken as
      symptoms of primary injury of the brain under conditions of burst polytrauma
      since increased activity of cytoplasmic and mitochondrial enzymes in the liquor
      is directly proportional to the brain trauma degree. The primary injury of the
      brain is characterized by a specific immune response: increased concentration of
      IgG, IgA in the liquor with the increased circulation of immune complexes.

PMID- 9027050
TI  - [Gunshot wounds of the abdomen].
AB  - Results of an analysis of 1404 cases of gunshot penetrating wounds of the abdomen
      and 451 thoracoabdominal wounds got by servicemen during the war in Afghanistan
      (1979-1989) are presented. Under consideration are the character of injuries of
      organs of the abdominal cavity, the operative procedures performed, the
      postoperative treatment, complications and outcomes.

PMID- 9027052
TI  - [Comparative results in gunshot and non-gunshot nerve injuries].
AB  - An analysis of clinico-neurological and electrophysiological examinations of 88
      patients before and during the operation enabled the authors to establish
      substantial pathomorphological and functional distinctions of gunshot and not
      gunshot injuries of the nerves, difference in results of various operative
      procedures.

PMID- 9027053
TI  - [Brachydactyly of the hand].
AB  - The author has analyzed 54 patients aged from 9 months till 14 years with one of
      the types of congenital underdevelopment of fingers-brachydactyly. This form of
      the congenital pathology of the hand is concretized, the X-ray and clinical
      picture of brachydactyly is analyzed and more exact classification of this
      pathology is given. The state of blood supply, innervation and histological
      structure of the abnormal hand tissues are studied. Methods of treatment are
      determined.

PMID- 9027054
TI  - [The vascularization characteristics of free transplants of the growth zones of
      the long tubular bones (experimental studies)].
AB  - The authors have studied the process of revascularization of free transplants of
      growth zones of the bones transplanted heterotopically from greater trochanter of
      the femur onto the chest. The X-ray and histological data have shown the ingrowth
      of the vessels into autotransplants from the side of soft tissues of the
      recipient bed responsible for the growth of the epiphyseal cartilage.

PMID- 9027055
TI  - [The use of the Ender nail in the osteosynthesis of diaphyseal fractures of the
      femur in children].

PMID- 9027056
TI  - [An infected cavernous hemangioma of the greater omentum in a child].

PMID- 9027057
TI  - [Prolonged hydroperitoneum in the combined prophylaxis of postoperative adhesion
      formation].

PMID- 9027058
TI  - [The treatment of urological complications by percutaneous interventions in
      patients after kidney transplantation].

PMID- 9027059
TI  - [An erythrocyte suspension in Modegel in the treatment of acute gastrointestinal
      hemorrhages].
AB  - The effectiveness of a suspension of erythrocytes in the new colloid preservative
      "Modegel" (in 1:1 ratio) was studied in the complex treatment of 31 patients with
      severe gastroduodenal bleedings. It was established that the hemodynamic,
      antianemic action of the suspension was not inferior (and even excels) to the
      action of the whole preserved blood and the erythrocytic mass. The suspension
      transfusion has a favorable effect upon functions of the liver and kidneys,
      corrects the acidic-alkaline state of the recipients' blood, decreases the lipid
      peroxidation and has detoxicating properties. During transfusion of the
      suspension hypocoagulation of blood doesn't take place. The temperature reactions
      following the suspension transfusion are rare. The suspension of erythrocytes
      "Modegel" deserves wide introduction to clinical practice.

PMID- 9027060
TI  - [Intra-articular oxygen administration in the combined treatment of hemophilic
      arthropathies].

PMID- 9027061
TI  - [A method for correcting gastric hemodynamics in duodenal peptic ulcer].

PMID- 9027062
TI  - [A new method for recording the spinal blood circulation in spinal diseases and
      trauma].

PMID- 9027063
TI  - [An intraductal choledochal elevator].

PMID- 9027064
TI  - [The diagnosis of arteriovenous malformations of the brain by transcranial
      dopplerography (the potentials of complex noninvasive neurosonoradiological
      diagnosis)].
AB  - Under analysis were results of diagnostics in 89 patients with suspected
      arteriovenous malformations (AVM) obtained by the method of ROC-analysis. The
      examination included computed tomography (CT) and transcranial dopplerography
      (TCDG) performed by the standard method. The total sensitivity of TCDG in
      diagnosing AVMs as a nosological form was 89.5% which is considerably higher than
      the possibilities of CT. Malformation having a torpid course were diagnosed
      correctly reliably more often (100%) than those with hemorrhagic debut (78.6%).
      Most perspective is the principle of unity of "morphological" and functional
      methods of noninvasive diagnostics. Sensitivity of the complex diagnostics of
      AVMs was 92.9%, diagnostics of malformations with a torpid course being without
      errors.

PMID- 9027065
TI  - [The determination of the level of esophageal resection taking into account its
      blood supply].
AB  - The anatomical and polarographic investigations allowed the authors to establish
      two critical portions for forming the esophageal anastomoses. Risk of
      incompetence of the anastomoses in these portions is great because of an
      insufficient blood supply.

PMID- 9027066
TI  - [Ways to improve the care of patients with suppurative surgical diseases].

PMID- 9027067
TI  - [Reconstructive operations in peptic ulcers of the gastroenteric anastomosis
      following gastric resection].
AB  - In 78 from 121 patients with peptic ulcers the cause of the appearance of the
      ulcer was the insufficient volume of resection of the stomach. As a rule
      resection was performed with transformation of gastrojejunal anastomosis into
      gastroduodenal one with the abdominal bilateral subdiaphragmatic vagotomy. The
      isolated vagotomy in peptic ulcers after resection of the stomach was not
      fulfilled as a rule. Vagotomy was not used for the treatment of peptic ulcers
      after gastroenteroanastomosis.

PMID- 9027068
TI  - [The surgical treatment of colonic cancer].

PMID- 9027069
TI  - [The importance of liquid-crystal thermography in selecting the therapeutic
      procedure and method of the operation in patients with an epithelial coccygeal
      cyst at the acute inflammation stage].

PMID- 9027070
TI  - [Difficulties in differential x-ray diagnosis of restrictive pneumothorax in
      young children].
AB  - To define X-ray signs of restrictive pneumothorax, the authors analyzed X-ray
      films of 225 newborns and babies of the first 3 months of life who were examined
      for respiratory disorders and acute respiratory diseases. Restrictive
      pneumothorax was detected in 19 (8.44%) infants. In 14 patients, gas was present
      in limited areas of various portions of the pleural cavity, without causing
      collabation of the lung and displacing the mediastinum, which makes diagnosis
      difficult. Moreover, the thoracic superimposition of the border of the scapula,
      soft tissue of the shoulder, hypoventilation of the lower lobe simulated
      restrictive pneumothorax in 38 children. Examinations in the lateral position on
      the healthy side, X-ray made in milder modes than as accepted, dynamic studies
      were helpful in diagnosing restrictive pneumothorax. However, additional X-ray
      study increased radiation loads. The concordance of X-ray images of the available
      X-ray films on a UAP-2 device in 47 children enabled the presence of pneumothorax
      to be specified by the segregated outlines of the partially collabated lung and
      by the absence of a lung pattern outside. In hypoventilation of the lower lobe, a
      lung pattern was identified both in the hypoventilated and in the normal midlobe.
      The processing of X-ray films on the UAP-2 device enhanced the accuracy of
      restrictive pneumothorax diagnosis in infants and made it possible to do away an
      additional X-ray study, which reduced radiation loads.

PMID- 9027072
TI  - [Analysis of x-ray manifestations and changes in dysplastic lesions of the skull
      bones].
AB  - The paper deals with the analysis of X-ray manifestations of osteodysplasia of
      skull bones in 136 patients of different ages. It presents the time course of
      changes in relation to the structural pattern of malformed osseous tissue,
      including those after radical and palliative surgical interventions.

PMID- 9027071
TI  - [Experience in clinical use of paramagnetic agent magnevist in the diagnosis of
      spine and spinal cord metastases].
AB  - Fifty six patients with suspected spinal metastases were examined. A diagnostic
      algorithm included native and contrast (the paramagnetic contrast agent magnevist
      (Shering) magnetic resonance tomography (MRT) of the spine and spinal marrow. The
      diagnosis of spinal metastases was verified in all patients examined by using
      magnevist. Spinal metastases most commonly gave rise to the breast (55%),
      prostate (20%), lung (10%). The results of the study provide evidence that the
      use of magnevist enhances the informative value and specificity of MRT in the
      diagnosis of spinal metastases.

PMID- 9027073
TI  - [Role of transcatheter embolization in intrahepatic arterioportal fistulas].
AB  - The treatment outcomes were analysed in 37 patients with intrahepatic
      arterioportal fistulas (IAPF) of various etiology. In 21 patients with fistulas
      in the presence of hepatoma, surgical resection (n = 4), hepatic arterial
      embolization with a hemostatic sponge and metallic spirals (n = 7) and
      conservative therapy (n = 10) were used. In 4 large iatrogenic IAPF, embolization
      was conducted just after making a diagnosis; in other 7 cases, a follow-up was
      accompanied by control arteriography. Embolization was done in all 5 patients
      with large spontaneous IAPF in the intact and cirrhosis- or hemangioma-related
      liver. One fatal outcome was observed after embolization in the presence of
      severe hepatic failure. No other complications were registered. Symptoms of
      elevated pressures in the portal vein regressed in most patients. It is concluded
      that despite the cause of occurrence, long-term IAPF results in hyperkinetic
      portal hypertension, followed by bleeding from the esophageal and gastric
      varicosity. Arterial embolization of IAPF in the hepatoma reduces the risk for
      fatal hemorrhage. Small iatrogenic IAPF should be followed up by making control
      arteriography. Arterial occlusion is the treatment of choice for spontaneous and
      persistent iatrogenic IAPF. Severe chronic hepatic failure is a contraindication
      for embolization.

PMID- 9027074
TI  - [Clinical effectiveness of x-ray contrast studies of muscles in patients with
      diseases of the locomotor system].

PMID- 9027076
TI  - [Radiographic study of the kidneys in children].

PMID- 9027075
TI  - [An algorithm of neuroradiological examination of patients with acute
      craniocerebral injuries].

PMID- 9027077
TI  - [Contrast enhancement computerized tomography in children under the conditions of
      a diagnostic center using nonionic preparation ultravist (Schering)].

PMID- 9027078
TI  - [Comparison of standard and asymmetric screen-film systems in thoracic
      radiography].

PMID- 9027079
TI  - [X-ray manifestations of jaw bones in adults].

PMID- 9027080
TI  - [Computerized tomography diagnosis of lymphadenopathies in malignant non
      Hodgkin's lymphomas].
AB  - The potentialities of computer-aided tomography (CAT) in the diagnosis of
      lymphomas were studied. A total of 223 patients with disseminated lymphadenopathy
      were examined (78 with malignant non-Hodgkin's lymphomas, 48 with Hodgkin's
      disease, 54 with metastatic involvement of the lymph nodes, 18 with HIV
      infection, and 25 with reactive and inflammatory lymphadenopathy). CAT helped
      precisely assess the dissemination of the pathological process and disease stage
      in patients with malignant lymphomas, permitted follow up the time course of the
      disease, and facilitated differentiation of the condition from other diseases
      manifesting by disseminated lymphadenopathies.

PMID- 9027081
TI  - [X-ray and radionuclide methods in the diagnosis of osteoporosis].

PMID- 9027083
TI  - [Training of radiologists in America].

PMID- 9027082
TI  - [75th anniversary of the Kharkov Research Institute of Medical Radiology].

PMID- 9027084
TI  - [The initial results of organizing epidemiological health surveillance in the
      transition to the territorial principle of medical support for the troops].

PMID- 9027085
TI  - [The prediction of the needs of the medical service for military physicians].

PMID- 9027086
TI  - [Automation of the management of the academic process in a military medical
      department].

PMID- 9027087
TI  - [The structure of morbidity of the oral cavity in recruits and officers of the
      Russian Army].

PMID- 9027088
TI  - [Posttransfusion immunosuppression].

PMID- 9027089
TI  - [The objective assessment of trauma severity].
AB  - The authors offer a technique of an estimation of traumas gravity on the base of
      two parameters: weight of damages and gravity of condition of injured. For
      quantitative estimation of weight of damages on the faculty of military-field
      surgery of the Military-medical academy a scale was developed, including 74 the
      most distributed damages, having from 0.05 up to 19 numbers. The weight of
      damages is estimated by assignment to a specific trauma an appropriate number. At
      multiple and combined traumas the numbers are summarized in accordance with
      special technique. The estimation of gravity of an injured condition is made on
      two estimated scales, having accordingly 12 and 16 the most important attributes.
      One scale is used for estimation of weight of injured condition in medical
      establishments, and the other scale-for estimation of condition gravity at the
      various stages of treatment.

PMID- 9027090
TI  - [The diagnosis and treatment of gunshot wounds of the rectum].

PMID- 9027091
TI  - [The means for improving therapeutic care in the Navy].
AB  - The army elements of the medical service, as the results of the checks have
      shown, have more than 80% of all defects of the therapeutic care providing at the
      fleet. Specific character of work of the ships doctors consists in long duration
      of the services, during which the doctor should independently decides any
      problems of providing medical care. Growing threat of large-scale radiating and
      toxicological disasters, presence at Naval Fleet of the seamen from the special
      contingent structure dictates necessity of the specialized medical care
      organization to appropriate categories of patients and injured.

PMID- 9027092
TI  - [The organization of prophylactic inoculations in the Far East Military
      District].

PMID- 9027093
TI  - [A method for measurements of the intensity of electromagnetic radiation].

PMID- 9027094
TI  - [The effect of smoking on morbidity and the disqualification of flight
      personnel].
AB  - From 369 pilots and navigators in the age of 35-36 years during 5-10 years in
      longitudinal research 163 healthy objects were observed. At healthy subjects
      probability of development of general new illnesses during nearest 5 years and
      disqualification on health condition are not connected with smoking in the age of
      35. In pilots and navigators with chronic diseases in the age of 35 smoking
      accelerates disqualification on health condition during 10 years. Till 45 years
      among disqualified on condition of health was much more smoking than nonsmoking.
      In essence it is important, that for pilots exists increased risk of loss of
      professional suitability on health condition in connection with smoking.

PMID- 9027095
TI  - [The prospects for using mobile units for radiation hygiene control in the Navy].
AB  - By one of ways of perfection of means and methods of the radioactive-hygiene
      irradiation doses control of personnel and radioactive contamination control of
      environment in the regions of dislocation of radioactive dangerous objects is
      creation of mobile complexes of the radioactive hygiene control, forming basis of
      mobile medical-economic complex (Zhiliaev E. G., Volodin A. S., Gavriutin V. M.,
      1995). In article a general characteristic of such complexes is given and example
      of practical use of one of typical mobile radiologic laboratories of domestic
      production as analogue of a mobile complex of the radioactive hygiene control.

PMID- 9027096
TI  - [Current trends in the development of new blood substitutes].

PMID- 9027097
TI  - [The 75th anniversary of the 2nd Central Polyclinic of the Ministry of Defense of
      the Russian Federation].

PMID- 9027098
TI  - [The anniversary of the Department of General and Military Epidemiology of the
      Military Medical Academy].

PMID- 9027099
TI  - [The 50th anniversary of the 9th Treatment and Diagnostic Center of the Ministry
      of Defense of the Russian Federation].

PMID- 9027101
TI  - [The anniversary scientific and practical conference of physicians of the 2nd
      Central Polyclinic of the Ministry of Defense of the Russian Federation].

PMID- 9027100
TI  - [Methodological problems in preserving the health of servicemen].

PMID- 9027102
TI  - [Prognosis of heart failure--value of drug therapy].
AB  - During the last decade medical treatment of congestive heart failure has made
      impressive strides. Several studies have proven that ACE-inhibitors improve
      symptoms and decrease mortality in patients with severe heart failure. ACE
      inhibitors have also been demonstrated to improve prognosis in patients with mild
      to moderate symptoms of heart failure as well as left ventricular dysfunction.
      However, long-term medical treatment of severe heart failure is only palliative.
      Despite treatment with high doses of ACE-inhibitors, 1-year mortality of patients
      with severe heart failure is as high as 36%. Therefore, at present, cardiac
      transplantation remains the only alternative treatment for patients with end
      stage congestive heart failure.

PMID- 9027103
TI  - [Percutaneous "high risk" angioplasty with prophylactic cardiopulmonary support.
      High risk PTCA with mechanical circulatory support].
AB  - With improved technology and development of several mechanical assist devices,
      the indications of percutaneous transluminal coronary revascularization have been
      extended. In 39 patients (30 men, mean age = 60.1 +/- 8.1 years) with angina
      pectoris or heart failure, with poor operative risk-benefit ratio and ejection
      fraction < 35% and/or target vessel supplying > 50% of the viable myocardium, we
      performed assisted percutaneous transluminal coronary revascularization.
      Intraortic balloon counterpulsation (n = 16), extracorporal circulation (n = 21),
      or hemopump (n = 2) were used for mechanical support. Complete 6-week follow up
      was possible in 27 patients. An improvement of left-ventricular function
      (patients with EF < or = 35% demonstrated an improvement: 27 +/- 7 vs 36 +/- 10%,
      p < 0.05), heart failure (patients with EF < or = 35% demonstrated an improvement
      of maximal oxygen uptake: 14 +/- 4 vs 17 +/- 4 ml/kg/min; p < 0.05) and a marked
      improvement of angina (23/38 demonstrated CCS-improvement of at least one class)
      was found. Hospital mortality was as low as 2.6%. Major postinterventional
      complications included nonfatal myocardial infarction (n = 2), fatal
      retroperitoneal bleeding (n = 1), pulmonary edema (n = 1), nonfatal ventricular
      fibrillation (n = 1), cerebrovascular event without residual (n = 1), and deep
      vein thrombosis (n = 4). In conclusion, assisted percutaneous revascularization
      was successful in a high risk subset of patients with increased surgical risk
      and/or poor ventricular function.

PMID- 9027104
TI  - [Initial clinical experiences with indirect myocardial revascularization--free
      skeletal muscle transplantation for induction of epimyocardial
      neovascularization].
AB  - Patients with multiple and peripherial coronary stenosis are not suitable for
      direct coronary artery surgery. For these patients a new surgical myocardial
      revascularization was developed. This new surgery was adopted on 5 patients from
      May 1993 through May 1995. The operation consisted in the grafting of a free
      skeletal muscle flap onto the anterior wall of the heart (musculus-latissimus
      dorsi). The flap artery was implanted into the aorta, the venous flow was
      directed into the right atrium. All patients were about 3 weeks after the
      intervention free from angina. The postoperative bicycle ergometry showed no
      signs of ischemic ST-segment changes, meanwhile the preoperative ergometry
      evinced signs of ischemic ST-segment changes in almost all patients.
      Angiographically a patent anastomosis of the flap artery implanted into the aorta
      was found as well as a good contrast of the graft. Thus, "indirect myocardial
      revascularization" may be a surgical alternative treatment for patients suffering
      from therapy refractory ischemic heart disease.

PMID- 9027105
TI  - [Surgical coronary revascularization of the beating heart].
AB  - Despite the fact that all the progress in technology, surgical technique and
      pathophysiological knowledge has made aortocoronary bypass surgery a safe routine
      procedure, there are certain clinical settings where an alternative approach
      seems to be advantageous. In 50 patients with age ranging from 51 to 74 years
      with advanced coronary heart disease and poor left ventricular (LV) function, as
      well as in patients with good LV function and single or double vessel disease not
      amenable for PTCA and in patients with acute ischemia or recent myocardial
      infarction, we performed coronary artery bypass grafting (CABG) without
      cardioplegic arrest during a short period of left ventricular unloading by means
      of a left ventricular assist device (LVAD). During LVAD support we administered
      Esmolol to decrease the heart rate and to keep the heart flaccid to facilitate
      easier peripheral anastomosis on a breathing heart. Preoperative ejection
      fraction ranged from 15 to 56%. In two patients of the acute MI-group, we
      continued the left ventricular mechanical support postoperatively, one of them
      survived. We performed on average 1,4 distal anastomoses and used in 34 cases the
      left internal mammary artery. All but three patients survived the procedure in
      stable conditions and could leave intensive care after a mean stay of 1.5 days.
      There were no perioperative myocardial infarctions. In our view, CABG during LVAD
      support without heart lung machine and cardioplegia is a safe and life saving
      procedure. No ischemic damage is applied to the heart and it can be recommended
      for cautions use in select patients.

PMID- 9027106
TI  - [Endoventricular patch-plasty for reconstruction of ventricular geometry and pump
      function in myocardial aneurysm].
AB  - This report deals with the first experience with endoventricular patch plasty in
      patients suffering from left ventricular aneurysm. The early postoperative
      results in 18 patients operated upon during January and May 1995 are encouraging.
      All patients survived the procedure. In contrast to patients operated on
      according to a linear resection technique the postoperative outcome and the early
      results are much better with this technique. We recommend the endoventricular
      patch plasty on a beating heart.

PMID- 9027108
TI  - [Acute and chronic mechanical circulatory support].
AB  - Mechanical circulatory support and mechanical unloading of the left ventricle
      become more and more routine in clinical treatment regimens of both acute and
      chronic heart failure. Along with increasing availability of different cardiac
      assist systems one can adjust the degree of support according to the clinical
      situation. We report about our experience in the period between January 1994 and
      May 1995 with following assist systems: Hemopump, centrifugal pumps, Medos,
      HIAVAD and Novacor. We implanted those devices in 21 patients out of following
      indications: postinfarct--cardiac failure (CF), postcardiotomy CF, elective
      postcardiotomy support, myocarditis CF and "bridge" to transplant. Ten patients
      survived the period of mechanical support and could be weaned successfully.
      Circulatory support was sufficient in all cases, indication, time of
      implantation, anticoagulation and prevention of infections are discussed.

PMID- 9027107
TI  - [Value of dynamic cardiomyoplasty].
AB  - The value of dynamic cardiomyopathy in the treatment of end-stage heart failure
      is controversial. After more than 500 patients have been operated worldwide, the
      indication and the surgical technique have become more uniform, which makes
      results from different centers eligible for comparison. We performed
      cardiomyopathy in patients with contraindications for heart transplantation.
      Between 8.90-2.94, 8 isolated cardiomyopathy-procedures in patients with
      cardiomyopathy (EF 14-32%, NYHA III) were performed. One patient died in 2 months
      after surgery. Reported are the results of 7 patients after a mean follow-up of
      41.1 +/- 14.1 months. Considerable symptomatic improvement was found in 6 of 7
      patients, 3 of whom went back to work. One patient with severe pulmonary
      hypertension exhibited no improvement. Mean NYHA-class decreased from 3.0 to 1.9
      (p < 0.001). Echocardiography showed an increase in fractional shortening in all
      patients. LV-EF increased from 21.2 +/- 5.2% to 38.1 +/- 15.9% (n = 7, p < 0.015)
      at 1 year, to 36.6 +/- 17.6% (n = 6, p < 0.05) at two years and to 36.4 +/- 18.9%
      (n = 5, NS) at three years. Pulmonary artery pressure tended to decrease at rest
      over time. No significant change in exercise level and maximal O2-consumption
      upon treadmill testing was observed. One patient died 34 months after the
      operation from sudden death. Our preliminary results show, that patients after
      cardiomyopathy may exhibit an impressive clinical improvement with less striking
      changes of objective hemodynamic parameters. This data is in mutual agreement
      with all other investigators. According to the current state of experience with
      cardiomyopathy, the place for this procedure lies in the treatment of patients
      with end-stage heart failure and contraindications for heart transplantation. We
      do not consider cardiomyopathy an alternative to heart transplantation, however,
      it may receive further importance as a bridge to Htx.

PMID- 9027109
TI  - [Orthotopic and heterotopic heart transplantation].
AB  - Orthotopic cardiac transplantation is an excellent palliation for endstage
      cardiac failure in select patients. Individual patients may benefit from
      heterotopic cardiac transplantation. Since 1986 88 patients received an
      orthotopic or heterotopic transplant at Charite University Hospital. 83% one year
      survival and 58% nine years-survival rates were achieved. Infection is a leading
      cause of death in patients after cardiac transplantation. Due to persistent
      scarcity of donor organs we have to consider alternative surgical methods as
      there are dynamic cardiomyopathy, and the chronic conventional surgery, and the
      chronic use of mechanical circulatory assist systems.

PMID- 9027110
TI  - [Pharmacotherapy of severe heart failure with inodilators--new approaches].
AB  - Severe congestive heart failure and cardiogenic shock don't resemble a
      homogeneous clinical picture, but a syndrome that is based on very different
      etiologies. What all the etiologies have in common is the inadequate peripheral
      O2-supply to essential organs with or without signs of severe pulmonary
      congestion up to pulmonary edema. For prognosis and therapy is a fast
      diagnostical clarification of the causes crucial. The therapeutical procedure for
      the various etiologies may be diametrically opposed. For the therapy is it also
      dicisive to distinguish between acute myocardial failure, e.g. acute myocardial
      infarction, and the development of myocardial failure from a longer existing
      consistent congestive heart failure (cardiomyopathy). Whenever possible, next to
      symptomatically therapy of cardiogenic shock the basic conditions of the disease
      should be cured (e.g., PTCA, lysis with acute myocardial infarction, lysis in
      acute pulmonary embolism). In myogenic cardiogenic shock the use of positive
      inotropic substances with and without simultaneous vasodilatory effects, if
      necessary in combination with other vasodilators, may be life-saving. Up until
      now there still doesn't exist an alternative to the catecholamines in the acute
      phase, initially they should be used as a first-line-therapy to stabilize the
      hemodynamics. The insertion of a Swan-Ganz-catheter for invasive therapy
      monitoring, especially for the regulation of the therapy is a "condition sine qua
      non" for every patient with unstable hemodynamics. Because of the prompt beta
      receptor-down-regulation during shock, caused by endogenous catecholamines,
      successful therapy with exogenous catecholamines is limited (adrenaline,
      dopamine, dobutamine), on account of the acceleration and intensification of the
      beta-receptor-down-regulation process. Possible beta-receptor independent
      alternatives are beta 2-agonists (dopexamine), PDE-III-inhibitors (amrinone,
      milrinone, enoximone) as well as H2-receptor agonists (impromidine, arpromidine)
      and finally the calcium-sensitisers (pimobendane). First results give rise to
      optimism to effectively reduce the mortality of congestive heart failure. The
      combination of these new pharmacological possibilities with interventional
      transcutaneous applicable assist-systems (aortic counterpulsationpump IABP,
      hemopump, transcutaneous heart-lung-machine) as well as the transitory
      application of an artificial heart (Novacor) can possibly increase the success of
      these therapeutic strategies. So far there are no convincing results shown in the
      world literature.

PMID- 9027111
TI  - [Indications for orthopedic surgery. What does the established orthopedist
      need?].

PMID- 9027112
TI  - [Forensic problems in the treatment of hip dysplasias and dislocations].

PMID- 9027113
TI  - [Late results of Salter's pelvic osteotomy].

PMID- 9027114
TI  - [Ability for military service in spondylolysis].

PMID- 9027115
TI  - ["Virtual reality" in published sciences?].

PMID- 9027116
TI  - [Segmental hypermobility of the spine before and following discectomy].
AB  - In 145 patients with open dissectomies (virgin back) preoperative functional x
      rays (flexion/extension) were available. 80 patients out of this group could be
      used for additional postoperative functional x-rays. The mean follow-up was 28 +/
      18 months. The segmental mobility was measured using the translation in the z-
      and the angular rotation about the x-axis (methods of Morgan/ King and Dupuis et
      al.). The patients were divided in 3 groups in respect to the level of operation.
      For each patient 3 segments (L3/4 to L5/S1) were analyzed. Segmental
      hypermobility was defined with a translation of more than 4 mm respectively a
      rotation of more than 18 degrees (ROM flexion/extension). In patients operated at
      the level of L4/5 (n = 62) segmental hypermobility was found in 12.9% at L3/4, in
      8.1% at L4/5 and in 17.7% at L5/S1. Patients with a discectomy at the level of
      L5/S1 (n = 79) showed preoperative hypermobility in 10.1% at L3/4, in 15.1% at
      L4/5 and in 12.6% at L5/S1. In postoperative x-rays patients with discectomy at
      L4/5 (n = 34) showed no significant differences after operation, neither in
      translation nor in rotation. In the L5/S1-discectomy group (n = 45) the mobility
      for rotation at the level L4/5 increased significantly from 6.7 degrees to 10.2
      degrees and in the level L5/S1 from 5.2 degrees to 8.4 degrees. There was no
      significant difference for the translation in all 3 segments. In both discectomy
      groups the number of segments with hypermobility didn't change significantly
      after operation.

PMID- 9027117
TI  - [The interesting case report: spinal infarct with the picture of lumbar
      ischialgia].
AB  - The case we present here is that of a fifty-year-old male patient who first came
      to the Orthopedic Hospital for out-patient treatment suffering from symptoms of
      lumboischialgia. Shortly afterwards, he developed symptoms characteristic of
      paraplegia. It was only 21 days after the initial symptoms had manifest
      themselves that the tentative previous diagnosis, suspected "spinal infarct",
      could be confirmed by magnetic resonance tomography (MRT). Possibilities offered
      by differential diagnosis are discussed; the discussion is followed by an
      enumeration of this highly heterogeneous group of illnesses.

PMID- 9027118
TI  - [Computerized tomography monitoring of the position of pedicle screws in
      scoliosis surgery].
AB  - With the increasing use of pedicle screws in instrumented spine surgery the
      neurological risk must be evaluated critically. Studies, which evaluated the
      accuracy of pedicle screw placement in scoliosis surgery, have not been published
      up to date to our knowledge. In 25 consecutive patients with idiopathic
      scoliosis, who underwent posterior instrumented curve correction and
      stabilization, the accuracy of pedicle screw placement was evaluated using axial
      computed tomography. There was a total of 178 screws between T5 and L4. The
      preoperative Cobb angle of the curve averaged 60.7 degrees, the mean rotation of
      the instrumented vertebrae was 19.1 degrees according to Perdriolle. 145 pedicle
      screws (81.5%) were placed correctly within the pedicles, of which 4 screws
      (4.5%) penetrated the anterior aspect of the vertebral body with a mean of 0.9
      mm. 22 screws (12.4%) showed lateral penetration of the pedicle with a mean of
      1.9 mm, of which one screw was placed completely lateral of the pedicle. 8 screws
      (4.5%) penetrated the medial wall of the pedicle by 1.3 mm on average. One screw
      each penetrated the cranial and caudal border of the pedicle. Statistical
      analysis did not reveal any significant relationships between pedicle screw
      misplacement and grade of vertebral rotation or site of instrumentation.
      Neurological complications were not noted in any of the cases. In our mind the
      risk of pedicle screw threaded curve correction and fusion in scoliosis surgery
      in the hands of an experienced spine surgeon is calculated acceptably low.

PMID- 9027119
TI  - [Asymmetry of posture and truncal musculature following unilateral arm amputation
      -a clinical, electromyographic, posture analytical and photogrammetric study].
AB  - Unilateral upper limb amputation causes changes in statics of the spine. As a
      result asymmetrical posture of the spine, muscular asymmetries follow. In this
      study a population of upper limb amputees (above and below elbow amputees) is
      examined by clinical, electromyographical analysis and gait analysis. Upper limb
      amputations cause in correlation to weight loss a shift of the trunk to the side
      of the amputation, a scoliosis with a bowing to the side of the amputation, an
      elevation of the shoulder on the amputation side and a torsion of the trunk.
      Muscular asymmetries result from loss of function (muscles of the arm, M.
      latissimus, M. trapezius) and by shifting of the center of gravity. In order to
      get the center of gravity over the legs, the amputee compensates the loss of
      weight by shifting the upper trunk to the side of the amputation. As a result the
      shift of the segmental center of gravity at the lumber height to the side of the
      normal arm with muscular asymmetry in the erector trunci lumbalis results. As
      well we saw an overactivity of musculus glutaeus medius and resulting stress of
      the amputation sided hip joint. There was a remarkable difference between above
      and below elbow amputees caused by differences in weight loss. Muscular and
      static asymmetries in amputees who lost their arm only a short period before
      could be reduced by compensating the weight loss. Results for technical
      orthopaedic fitting and stress on gymnastic procedures to compensate these
      statistical problems are discussed.

PMID- 9027120
TI  - [Special case report: Gangrene of all 4 extremities caused by disseminated
      intravascular coagulation in pneumococcal sepsis].
AB  - The rare case of a child with gangrene of all extremities following intravascular
      coagulation in pneumococcus septicaemia is described. The two years old spanish
      girl showed a gangrene of all four extremities and accompanying celloid scars.
      The operative treatment, the orthopaedic technical fitting as well as the
      problems are discussed.

PMID- 9027121
TI  - [Surgical amputation and prosthetic management in congenital fibrosarcoma of the
      lower extremity].
AB  - The concept of surgical amputation and the problems of prosthetic management in a
      girl with congenital fibrosarcoma of left distal thigh, knee and shank is
      described. After failed polychemotherapy (EICESS 92) and expansion of the tumor a
      radical knee disarticulation and intended marginal resection of the tumorous soft
      tissue area of the distal thigh was performed at the age of eleven months and two
      weeks. The femur was shortened by osteotomy of the diaphysis and removing a
      fragment in order to protect the distal femoral epiphyseal growth plate and to be
      able to close the soft tissue of the stump primarily. Prosthetic fitting and
      rehabilitation started at the beginning of statomotorical development at the
      point when four feet standing changed into two feet standing. In present, at the
      age of two years and six months, this girl is independent mobile and well fitted
      with a knee disarticulation prosthesis.

PMID- 9027123
TI  - [Sesamoid bone complex and hallux valgus deformity. A retrospective analysis of
      82 Mitchell osteotomies].
AB  - The aim of the operative treatment of the hallux valgus deformity is to correct
      the medial luxation of the first metatarsal head out of the sesamoid complex, the
      restoration of a congruent joint, the patient after treatment should be painfree.
      82 patients were available for an independent clinical and radiological review.
      The median follow up was 32 months. The evaluation of the results are based on
      objective and subjective assessment of the patients as well as on radiographic
      criteria, such as hallux valgus angle, intermetatarsal angle, shortening of the
      first metatarsal bone, subluxation, lateral positioning of the osteotomized MT I
      head and position of the sesamoid complex. Depending on the degree of
      "lateralisation" of the sesamoid complex seven groups were defined: 0/0, 1/0,
      1/1, 2/1, 2/2. 2/3, 3/3 following Appel. Following objective criteria 61% of the
      patients were evaluated excellent or good, following subjective criteria 77% were
      evaluated excellent or good. Isolated parallel shifting seems to be sufficient in
      mild forms of hallux valgus (sesamoid complex group 2/2 or less), while the
      severe subluxation in the metatarsophalangeal joint (sesamoid complex group 2/3,
      3/3) requires an additional lateral wedge osteotomy.

PMID- 9027122
TI  - [Surgical treatment of a bunionette].
AB  - The term Bunionette or Tailor's Bunion is applied to an abnormal prominence on
      the lateral aspect of the fifth toe similar to the Hallux valgus of the first
      ray. Several different operative procedures-proximal, diaphyseal or distal-are
      advocated. Our analysis compares the clinical and radiological results of the
      distal oblique osteotomy and the distal Chevron metatarsal osteotomy. The
      clinical evaluation is based on the "Mayo Clinic Forefoot Scoring System" (max.
      75 points). Radiographic examination includes measurement of the fourth to fifth
      intermetatarsal angel, the fifth metatarsal phalangeal angel, as well as the
      shortening of the fifth metatarsal ray. Overall clinical results were evaluated
      as very good in both surgical techniques, all the patients obtained more than 70
      points in the score. The radiographic analyses show an improvement of the
      "functional angels" (IMT IV-V, MTP V) with both osteotomies. In all the cases of
      the distal oblique osteotomy there was a shortening of the fifth metatarsal bone
      and sometimes a tilting of the head with a consecutive "malalignment" of the
      metatarsal row without clinical impairment. The Chevron procedure resulted in
      correct positioning of the metatarsal head in all patients.

PMID- 9027124
TI  - [Arterial blood flow in congenital idiopathic clubfoot].
AB  - A doppler ultrasound study investigated vascularity in congenital idiopathic
      clubfeet (talipes equinovarus, (TEV) pretreated only by casting and
      physiotherapy. The studies were performed on 40 TEV (27 patients) aged 4-72
      months (average 15.1). In 12 unilateral cases of TEV, the opposite normal foot
      and 74 normal feet of 37 healthy children aged 3-35 months (average 8.7) were
      used as controls. Dorsalis pedis (DP), posterior tibial (PT), and peroneal (P)
      pulses were recorded by an unidirectional 8 MHZ continuous wave technique. At
      rest, DP pulses and PT pulses were present in all investigated TEVs. P pulse was
      absent in only one case of TEV. In the group of controls DP pulse was absent in
      one case and P pulse was absent in an other case of normal foot with
      contralateral TEV. All the other pulses in normal feet were present at
      physiological location. We propose that a vascular etiology for the origin of
      congenital idiopathic clubfoot, as reported in literature, is unlikely. The
      influence of postnatal casting in TEV on the vascular arterial condition is
      slight or even absent. Doppler assessment is readily available, noninvasive, and
      a reproducible mean of monitoring vascular integrity in clubfeet. Relating to
      vascular complications after surgery, perhaps caused by a preextant arterial
      anomaly, doppler assessment is indicated routinely in syndromes of multiple
      malformations with clubfoot deformity before surgical treatment. In congenital
      idiopathic clubfeet it is not necessary as a routine check.

PMID- 9027125
TI  - [Combined caudal and general anesthesia in clubfoot surgery].
AB  - In a retrospective study we analysed the effect of caudal epidural anesthesia
      combined with general anesthesia on requirement for intraoperative narcotics and
      postoperative analgesics in children undergoing surgical release of congenital
      clubfoot. In 20 children (mean age at day of surgery 4,7 months) general
      anesthesia was supplemented by caudal epidural anesthesia, controls (20 children,
      mean age 4,3 months) received general anesthesia only. Compared to controls, the
      amount of narcotics was significantly reduced in the caudal epidural group (1,1
      Vol% compared to 1,6 Vol% Isofluran). As well the use of analgesics in the
      postoperative phase was decreased from 112,5 mg to 56,3 mg Paracetamol. The
      children in the caudal epidural group recovered from anesthesia more comfortably.
      No complications occurred in either group. Our results show, that general
      anesthesia combined with caudal epidural anesthesia is more suitable for surgical
      release of congenital clubfoot than the exclusive use of general anesthesia.

PMID- 9027126
TI  - [Treatment of congenital tibial pseudarthrosis using a free vascularized fibula
      transfer and plate osteosynthesis. Case report].
AB  - Congenital pseudarthrosis of the tibia is a rare disorder of unknown etiology.
      The free vascularized fibula-pro-tibia-transplant permits correction of the
      defect and the leg length-discrepancy during one surgical procedure. A 5 year old
      girl with congenital pseudarthrosis underwent a free vascularized fibular-pro
      tibia-transplant. At a follow-up examination 5 years post surgery she had no
      subjective complaints, she walked without external orthopaedic support, there was
      no leg length-discrepancy. As stated in the literature the rates of bony unions
      are much higher than after conventional methods.

PMID- 9027127
TI  - [Arthroscopic repair of the glenoid labrum using the 3-point knot technique.
      Early results with consideration to different postoperative immobilization time
      periods].
AB  - There are different opinions on the duration of post-operative shoulder
      immobilisation following arthroscopic repair of labrum tears. Between 1993 and
      1994 at our department arthroscopic repairs of the glenoid labrum as described by
      Habermeyer (15, 16) have been performed in 38 patients. In 20 of these patients
      postoperative treatment included immobilisation of the operated shoulder in a
      Gilchrist-bandage for 3 weeks, while in the remaining 18 patients this
      postoperative immobilisation period was decreased to only 1 or 2 weeks.
      Physiotherapy started the day after the operation, using a device for passive
      motion exercises. The mean follow-up time of our examinations was 15.4 month. The
      mean score by Rowe rose significantly from 20.0 preoperatively to 82.6 at the
      follow-up examination. Results were excellent or good in 89.4% of all cases, new
      shoulder dislocations did not occur in any case. Patients having their shoulders
      immobilised for 3 weeks reached significantly higher Rowe-scores at our follow-up
      than those patients, whose shoulders were immobilised for only 1 or 2 weeks.
      Therefore, postoperative management following arthroscopic repair of labrum tears
      should include immobilisation of the operate shoulder for 3 weeks and an early
      start of passive-motion exercises.

PMID- 9027128
TI  - [Epidemiology of stress fractures from an occupational health viewpoint].
AB  - Stress fractures may occur after extremely high exercises in sports, military
      training, and occupational activities. The pathogenetic mechanisms include
      processes of material fatigue as well as repair capacities of the bone. By means
      of szintigraphic technique a sensitive tool for diagnostics of stress fractures
      is available. Recently, stress fractures of the vertebral processes only are
      acknowledged as a professional disease in Germany. As a rule, in orthopaedic and
      surgical practice fatigue fractures of other bones are considered as cases of
      accidental injuries.

PMID- 9027130
TI  - [Discussion remarks and opinion on: N. Wulker, K. Thren, M. Korell and L. Kirsch:
      Measurements in the translation of the glenohumeral joint in a dynamic shoulder
      model. Z. Orthop. 133 (1996) 67-72].

PMID- 9027129
TI  - [Experimental studies of mechanically-induced articular cartilage defects
      following implantation of allogeneic embryonal chondrocytes in a collagen-fibrin
      gel in chickens].
AB  - Full thickness defects (diameter 1,7 mm; depth 2,5 mm) were created mechanically
      in articular cartilage and subchondral bone of the condyles of tibiotarsal joints
      of 9-month old chickens. This full-thickness defects were repaired with cultured
      allogenic embryonic chick epiphyseal chondrocytes from the tibiae and femura of
      10-days-old chicken embryos. The cells were embedded in a collagen-fibrinogen
      matrix. Controls were similarly operated, but received either no treatment or
      implants the delivery substance only. Healing of the defects was observed
      macroscopically, histologically, histochemically and histomorphometrically after
      3, 12 and 24 weeks. This graft was successfully transplanted in mechanically
      induced defects in 80%. The resulting hyaline cartilage was structurally
      reorganized according to the host pattern and under the influence of
      environmental conditions. The articular zone preserved it's cartilaginous
      phenotype, whereas the subchondral regions were transformed into bone. 12 weeks
      after the operation the defects in the experimental group were completely filled.
      In all instances in this group, there was an initial extreme increase of mitotic
      rate and cell number. After 24 weeks normal and subnormal values were founded.
      The defects in the control groups healed with fibrocartilage. Our results showed,
      that only the defects in the experimental group were completely filled with
      reparative hyaline cartilage tissue. In the present study the mixture of cultured
      allogenic embryonic chondrocytes and a collagen-fibrinogen-matrix was used
      successfully as a transplant for repairing defects in articular cartilage of
      chickens. Thus allogenic transplantation of cultured embryonal chondrocytes
      appears to be one of the most promising methods for the restoration of articular
      cartilage.

PMID- 9027131
TI  - [Re: W.U. Weitbrecht, W. Schafer, A. Walter: Is physiotherapy useful following
      carpal tunnel syndrome? Z. Orthop 133 (1995)429-431].

PMID- 9027132
TI  - [Jenner's cowpox vaccine in light of current vaccinology].
AB  - Two hundred years ago Edward Jenner inoculated James Phipps with vaccinia and 181
      years later smallpox had disappeared from the surface of the earth as a result of
      generalized vaccination. Compared to the requirements of modern vaccinology, the
      procedures used by Jenner and his successors, were extremely primitive because of
      an almost total lack of knowledge in the field of microbiology and immunology.
      The active principle of smallpox vaccine is vaccinia virus, which in many
      respects, differs from that of natural cowpox; the term "cowpox" has been used
      for more than a century and a half to designate the vaccine; it appears itself to
      be a misnomer, because it is most probably by a virus of rodents, which only
      occasionally infects bovines or other species, especially cats. The origin of
      vaccinia remains doubtful, but a plausible explanation is that it is derived from
      horse-pox. Jenner was convinced that he was working with a virus of equine
      origin, which was occasionally transmitted from the horse to the cow by the
      personnel on the farms. Horse pox has now completely disappeared. Especially
      during the first years after Jenner's discovery, great confusion was caused by
      other lesions on the cow's udder, which were called "spurious cowpox". We know
      today that these lesions could be caused by the viruses of papular stomatitis,
      pseudo-cowpox or para-vaccinia (milker's nodules), herpes mammilitis and
      papillomatosis; they could not be differentiated from those of cowpox or
      vaccinia, in addition lesions due to bacteria or other causes also led to
      confusion. During the first eighty years the vaccine was being transferred almost
      exclusively from arm to arm with the risks inherent in this procedure; one of the
      reasons for applying this method was the fear of "bestialization" thought to be
      linked with the use of material of animal origin. Several contaminations have
      been observed as a result of the use of the arm-to-arm procedure: smallpox was
      transmitted, especially in the beginning, because vaccinations were carried out
      in a contaminated environment. Syphilis was diagnosed in several countries after
      the use of vaccine taken from syphilis patients. At least two foci of hepatitis
      were reported after the use of contaminated human lymph. Transmission of
      tuberculosis or what was then designated as scrofulosis was unlikely, but was
      used as one of the main arguments against vaccination by the antivaccinists.
      Varicella and measles were transmitted from time to time with the vaccine and
      also bacterial infections, such as staphylococci, streptococci e.a. From the
      global point of view, however, the number of contaminations remained limited in
      comparison with the large numbers of vaccinations that were performed. Another
      problem the early vaccinators were facing, was that of the decline and
      disappearance of the immunity after a certain number of years. Jenner and his
      successors believed that the immunity post vaccination would be lifelong as it
      was after variolation. When in the early part of the 19th century more and more
      immunity breakdowns occurred, this observation led to total confusion and it took
      dozens of years of debate and controversy before the only logical and efficacious
      measure, i.e. revaccination, was generally accepted and implemented. In the last
      third of the 19th century "human lymph", obtained by arm-to-arm vaccination, was
      gradually replaced everywhere by animal lymph i.e. vaccine produced on the skin
      of animals, mainly calves. The determining factor in the switch was the risk of
      vaccination syphilis. Everywhere vaccine institutes were created, where the
      vaccinia virus was propagated on the skin of calves. The harvested virus served
      each time for the inoculation of fresh calves; this resulted in a gradual
      increase of the number of passages leading to the possible risk of
      overattenuation. To avoid this risk, passages in man, donkeys, rabbits or other
      species were performed from time to time.

PMID- 9027133
TI  - [Dental care using silver amalgam].
AB  - Dental amalgam is the most widely used filling material in dentistry. In our
      country there are an estimated 40 million amalgam fillings in place. The mercury
      present in these fillings has caused health concerns over the last 160 years that
      amalgam has been used in decayed teeth. The fears have always proven to be
      unjustified and no harmful effects have ever been demonstrated in dental
      patients. Mercury can be found in several forms. In dentistry, only the metallic
      form is used, while inorganic and organic compounds are also present in the
      environment. The metallic form is absorbed in the human body mostly through the
      lungs. Once mercury reaches toxic levels inside the body, it will interfere with
      cell metabolism. Most important among the target organs are the brain, the liver
      and the kidneys. Elimination occur through urine and feces. Mercury is
      universally found in blood and urine. The concentration depends on absorption by
      air, water, nutrition, medication (including dental fillings) and occupational
      hazards. There are four kinds of objectives to dental amalgam: oral galvanism,
      toxicity, allergenicity and ecological grievances. Disorders from oral galvanism
      are difficult and delicate to evaluate as the actual currents are very small.
      Furthermore, no significant difference can be found in current intensity between
      patients with and without complaints. Finally patients with complaints often
      present other oral disorders, the treatment of which most often eliminates all
      complaints that could be attributed to oral galvanism. Toxicity is dose
      dependent. Industrial safety rules indicate that the amount of mercury absorbed
      from dental amalgam fillings is far below the safety level. HgB and HgU levels in
      patients with amalgam fillings are situated well below the acceptable levels.
      Allergic disorders are observed in patients with amalgam fillings but far less
      than expected in view of the wide spread use of dental amalgam. The problem of
      mercury spilling from dental amalgam fillings into the environment will be
      resolved by strict legislation in the near future. In this context, it can be
      stated that the use of dental amalgam is safe and justified. Furthermore, it is
      also advisable as no other material can meet the actual dental needs as
      efficiently as can dental amalgam.

PMID- 9027134
TI  - [The selectivity of the mutagenic action of DNA and other polynucleotides].
AB  - A paper summarises the results of author's and his collaborators studies on the
      mutagenic action of DNA and other natural and synthetic polynucleotides. These
      results were published with rare exception in Russian and Ukrainian scientific
      journals. Analogous results obtained by other authors of several countries are
      also discussed. It was proved that unlike conventional physical and chemical
      mutagens, polynucleotides selectively induce visible and lethal mutations
      preferentially in certain genes, different in case of treatment with different
      polynucleotides. Polynucleotides often induce mutation in several non-allelic
      genes in a single germ cell of the host (multimutational effect). Polynucleotides
      do not induce gross chromosome aberration.

PMID- 9027135
TI  - [The biological design of the oxygen transport system in mammals and the law of
      symmorphism].
AB  - In oxygen transport system of mammals the most important are biological constants
      and peculiarities of system construction, that are only hardly regulated
      physiologically. Thus, the coefficient of oxygen diffusion in animal tissues
      determines the construction of lungs and microvessel systems, oxygen capacity of
      blood, the rates of haemoglobin oxygenation and oxyhaemoglobin desoxygenation.
      The important parameter of biological construction of oxygen transport system is
      relatively low heart power (1-1.5 Vt for human). Such low value can be explained
      by low resistance to blood flow in microvessels because of decrease in blood
      viscosity. According the law of simmorphism physiological functions have a
      reserve that allows approximately ten times increase in power of functions. This
      law should be corrected since the supposed reserves in relatively small mammals
      are almost completely run off even in the stage of rest for maintenance of
      temperature homeostasis.

PMID- 9027136
TI  - [The chemical interaction of tadpoles of the common frog Rana temporaria L. with
      conspecific and heterospecific anuran tadpoles].
AB  - In double-choice experiments the behavioural reactions of Rana temporaria
      tadpoles to con- and heterospecific chemical cues of anuran tadpoles were
      studied. It was shown that they have not reacted to heterospecific chemical
      signals but were attracted by co-specific ones. Besides, Rana temporaria tadpoles
      do not show chemical guided sibling-reaction, saying that the sibs' cues were not
      preferable. The results indicate that Rana temporaria tadpoles are capable to
      distinguish these signals, react to some of them and cause the reaction of other
      tadpoles. Nevertheless, chemical signals seem not to play such great role in
      communication of these tadpoles.

PMID- 9027137
TI  - [Investigation and evaluation of fumonisin contamination of native and imported
      cereals].
AB  - Cereal varieties cultivated in Germany, such as wheat, rye, grain-maize, barley,
      and oats were analyzed for fumonisins, including also imported maize from
      Argentina. In a total of 410 wheat samples and 140 rye samples of two harvesting
      years (1993, 1994) and in random samples of barley and oats no fumonisins were
      detected at all. In german grain-maize of 1993, only low fumonisin contents (17
      33 ng/g) were detected occasionally. Some grainmaize samples of the 1994 harvest
      contained significantly higher fumonisin amounts, partly up to the mg/kg-range,
      which obviously is due to the extremely high temperatures during summer. In some
      samples of variety tests of the country the fumonisin B1 content amounted up to
      4828 ng/g and the total fumonisin content (FB1-FB3) up to 7132 ng/g respectively.
      In 1994 a total of 317 native grain-maize samples was tested, of it 109 samples
      of German cultivation and 208 samples from variety tests of different federal
      states. Maize samples from Baden-Wurttemberg, which are representative to the
      maize harvest of this state, had a fumonisin contamination of 14%, the mean value
      of the contaminated samples amounting to 206 ng/g. Of the imported maize from
      Argentina, all the investigated 21 samples had a fumonisin content (FB1-FB3) of
      14-1106 ng/g, the mean fumonisin content amounting to 175 ng/g.

PMID- 9027140
TI  - [Sexual behavior of Italian youths in connection to AIDS risk].
AB  - The objective of this survey is to evaluate knowledge and sexual behaviour among
      young Italians (19 to 24 years). The project, began in 1993, is being carried out
      through an anonymous postal questionnaire, sent to a representative sample of the
      young Italian population (a total of 52,000 people from 363 Italian towns). In
      the present intermediate evaluation, we have analysed 6929 of the 18,132
      questionnaires sent till now, with all Italian regions being proportionally
      included. Our data show that, after sexual activity has been started, it hardly
      seems to be limited to monogamy or to be always regulated by AIDS-preventing
      practices. Data show that the age of the first sexual intercourse is increasing
      (after age 18) and that condoms are used more frequently, particularly in
      occasional sex.

PMID- 9027138
TI  - [Comparison of the efficacy of various strains of mumps vaccine: a school
      survey].
AB  - BACKGROUND: Since the beginning of the program of immunization of children
      against measles, mumps and rubella (MMR) in 1987, various outbreaks of mumps have
      occurred in Switzerland, with a significant proportion of cases in immunized
      children. Previous studies have suggested a possible lack of efficacy of the
      Rubini vaccine strain, which has been much used in this country. METHODS:
      Incidence study of secondary cases of mumps in the schools of Geneva, between
      March 18th and June 30th 1994. STUDY POPULATION: During the study period, mumps
      outbreaks have been observed in 10 school classes. After exclusion of the 10
      primary cases, the study population comprised 195 children aged 4 to 12 years.
      RESULTS: Raw estimation of vaccine efficacy against mumps was 72.5%. Whereas both
      the Urabe and Jeryl-Lynn strains showed a significant efficacy, the Rubini strain
      didn't show any significant protective effect. After adjustment by Poisson
      regressions for the confounding effect of age, efficacy rates and 95% confidence
      limits were 75.8% (35.6%, 90.9%) for Urabe; 64.7% (10.6%, 86.0%) for Jeryl-Lynn;
      and 12.4% (-102%, 62.1%) fur Rubini. CONCLUSION: This study didn't show any
      protective effect of the Rubini vaccine strain. Furthermore, it demonstrated a
      statistically significant protective effect of the Urabe and Jeryl-Lynn strains,
      compared to the Rubini strains. In this conditions the use of the Rubini strain
      should be restricted to situations of confirmed contra-indications to the other
      vaccinal strains, as long as its protective efficacy is not clearly demonstrated.

PMID- 9027139
TI  - [The distribution of selected cardiac risk factors in employed and studying
      youths in the rural region of Steiermark (Austria)].
AB  - Demographic data, components of lifestyles such as risk behavior, health
      complaints, illnesses and utilization of preventive and curative services were
      surveyed through a health survey conducted in 79 selected rural communities of
      Styria between 1989 and 1933. Our research focussed on the stratification of
      cardiovascular risk factors such as smoking, high blood pressure, unhealthy
      nutrition, low physical activity and obesity in adolescents employed or attending
      school. The sample comprises 1239 adolescents divided into two groups: 651 were
      employed and 588 were in school. We could show that even at such a young age
      significant differences occur in the distribution of cardiovascular risk factors
      between these two groups. The employed adolescents were far more stressed than
      those of their age group attending school. Generally, the females are less
      strained than the males. Our results suggest that efficient programs to prevent
      cardiovascular disease need to specifically focus on the various life contexts of
      young people. Such programs should start at an early date.

PMID- 9027141
TI  - [Illegal drugs: attitude of parents of adolescents].
AB  - A survey among 2000 mothers and fathers of adolescent children confirms parent's
      concern about illicit drugs. Close to 40% of the respondents fear that their
      child, aged 11 to 16 years, could develop a drug problem. Those parents with the
      most apprehensions are to be found in the French-speaking and the Italian
      speaking region of Switzerland. It is also worthy to note that those fathers and
      mothers who have the impression that they are well informed about drugs are less
      fearful than those who feel insufficiently informed. Approximately one quarter of
      those questioned report lack of knowledge about illegal drugs and one third of
      parents do not know whom they could turn to in case someone in their immediate
      environment should have a drug problem. Many fathers and mothers have only scant
      knowledge about psychoactive substances and their related health risks. Most
      parents regard drug use as a social phenomenon and therefore assume that their
      child will be confronted with illegal drugs sooner or later. In order to hinder
      youngsters from using drugs respondents wish more prevention and information
      among parents as well as among children at school. However personal interviews
      show that parents consider it a difficult task to discuss drugs with their
      children. Some hints for the prevention are outlined.

PMID- 9027142
TI  - [Dietary differences between restaurants and home in a representative sample of
      the adult population residing in Geneva].
AB  - Differences in dietary intakes between those who eat at home and those who eat at
      the restaurant have not been documented previously. In the present study, three
      registered dietitians interviewed 626 adult residents of Geneva on the telephone
      about their diet the day before. Interviews were distributed over the seven days
      of the week. Participation rate was 80%. Results show that men go more often to
      the restaurant than women, that young people have lunch at the restaurant more
      often than older people but that age is not related to having dinner at the
      restaurant. When a resident of Geneva goes to the restaurant to have dinner, he
      eats and drinks more than those who eat at home, but the relative content of
      proteins, lipids and carbohydrates of the diet is not different. In conclusion,
      in Geneva the diet at the restaurant is very similar to the diet at home. This
      suggest that the meals in a restaurant tend to adapt to the customer's
      expectations rather then the opposite. The potential implication for public
      health is that the priority is to inform the customer about what is a healthy
      diet, the restaurant owner will follow his client's need.

PMID- 9027143
TI  - [Variations in referral to specialized medical centers of the Swiss disability
      insurance: role of the referring party].
AB  - The Commissions of the Swiss Disability Insurance (CDI), in order to evaluate the
      degree of disability which determines the right to benefits, can call upon
      Medical Observation Centers (MOCD) for a pluridisciplinary examination. The
      utilization rate of the MOCD, by the 28 CDI, varies by a factor of 1 to 50. The
      goal of this study is to identify the causes of this variation related to the
      differences in CDI practice. The CDI answered a mail survey. For analysis, they
      are allocated into 3 groups of equal size: Low, medium and high users of MOCD.
      There is no association between the use of the official and non-official criteria
      for referral to MOCD and utilization rate of the MOCD. The CDI have a false
      perception of their MOCD use; 40% of them underestimate it. Considering together
      the utilization rate of the substitutes and of the MOCD, variation still persists
      from 1 to 9 among the CDI. There is no difference in the reasons for non-referral
      to the MOCD according to the level of utilization. This study failed to identify
      the causes of the utilization differences of the MOCD by the CDI. Other factors
      should be examined.

PMID- 9027144
TI  - [Case report on management of grade 4 infected open comminuted tarsus fracture by
      tibio-Chopart arthrodesis].
AB  - We report on the treatment of a 39 year old patient who suffered from subtotal
      amputation of the middle foot area after fall from tall height. He was treated by
      an arthrodesis between ventral tibia and distal Chopart-joint which was carried
      out as late-primary care. Therefore calcaneus and talus were totally and os
      cuboideum and os scaphoideum were partially removed. This form of arthrodesis is
      a rare indication. With remaining blood flow and sensibility in the fore foot it
      is an alternative to amputation/exarticulation in the tibiotalar joint.
      Advantages are the improved plantar weightbearing area, a simplified supply of
      orthopedic shoes and a better tactile ground contact.

PMID- 9027145
TI  - [Ludwig Rehn (1849-1930) and his importance in the development of modern
      surgery].
AB  - The unusual course of Ludwig Rehn's professional development directed him from a
      general practitioner close to Frankfurt am Main to his convocation as first
      Professor in ordinary for surgery to the Frankfurt University, which was newly
      established in 1914. Among his numerous publications, especially the following
      contributed immensely to the development of modern surgery: in 1884, he already
      described the healing of patients with Graves' disease by subtotal resection of
      the goiter; in 1885 he first described the high prevalence of bladder tumors in
      workers of an aniline factory; in 1886, he managed the first successful heart
      suture after a stab-incision of the right ventricle; in 1897, he already
      performed an operation at the thoracal oesophagus, with an access via the
      posterior mediastinum; in 1920, he established the operative treatment
      (pericardectomy) of patients with a calcified pericarditis (armour heart).

PMID- 9027146
TI  - [Management of polytrauma].

PMID- 9027147
TI  - [Pathophysiology of polytrauma].
AB  - Sequential organ failure after multiple trauma emerges from a whole-body
      inflammatory process which develops as a complex host defense response to
      hypovolemic shock/resuscitation and traumatic tissue injury. Successful
      prevention and treatment involves exact assessment of inflicted damage and
      profound knowledge of the different stages of posttraumatic immune alterations.
      Local release of potent inflammatory mediators (cytokines, complement,
      arachidonic acid derivatives, reactive oxygen metabolites) primarily induces a
      repair process. However, massive soft tissue and bone injury, follow-up surgery,
      infections and blood transfusions trigger a systemic spill over of these
      mediators orchestrating a generalized inflammatory response (Systemic
      Inflammatory Response Syndrome, SIRS). Diffuse capillary leakage and
      microcirculatory disorder prepare cellular dysfunction. Secondary severe immune
      defects support septic complications which maintain an autodestructive process.
      Therapeutical advances depend on the analysis of local and time-dependent
      expression of relevant inflammatory mediators and cellular signalling systems.

PMID- 9027148
TI  - [Value of clinical scoring systems for evaluation of injury severity and as an
      instrument for quality management of severely injured patients].
AB  - Trauma Score Systems attempt to summarize the severity of injury in a single
      value. They provide a better classification of trauma patients and translate
      different severities of injury in a common language. They enable thereby
      comparisons between hospitals or trauma systems. Young doctors can control their
      clinical judgement with scoring systems and will gain experience. Scoring systems
      therefore increase safety and can help in decision making. As accuracy of scoring
      systems is never 100% individual decisions can never rely on scores only. Glasgow
      Coma Scale, Revised Trauma Score, Injury Severity Score and TRISS are the most
      often used international scores for severely injured patients. Their sensitivity
      and specificity, validity, reliability and practicability have been studied and
      proved in many trials. The role of these scoring systems for quality management
      purposes in the treatment of severe trauma is actually studied with the Trauma
      Registry of the German Society for Trauma Surgery.

PMID- 9027150
TI  - [Shock room management of polytrauma].
AB  - The emergency room functions as a junction between preclinical and early clinical
      treatment of patients with multiple trauma and should have defined technical and
      room possibilities. The personal staff should continue resuscitation measures and
      perform clinical and technical diagnostic procedures according to trained
      algorithms. The recognition of life-threatening injuries, the set up of correct
      priorities and application of respective surgical procedures characterize a good
      emergency room management.

PMID- 9027149
TI  - [Emergency management of polytrauma patients].
AB  - Adequate prehospital care of the severely traumatised patient is important to
      prevent or attenuate early as well as late life threatening complications, such
      as tissue hypoxia, ischemia/reperfusion injury and finally multiple organ
      failure. A mismatch of oxygen supply and oxygen demand is a hallmark in the
      pathophysiology of multiple trauma. Oxygen supply may be diminished by the
      following factors: shock-related decrease of cardiac output, anemia and hypoxia.
      On the other hand, oxygen demand may be increased by pain, panic, and agitation.
      Hence, it is a central point in prehospital care to reduce this supply-demand
      imbalance by identification and prompt reversal of the underlying causes. Most
      often, shock is caused by hypovolaemia and tissue injury ("traumatic-hemorrhagic
      shock"). However, shock may also be a result of central nervous system injury
      (neurogenic shock as a special form of distributive shock) or circulatory
      obstruction, e.g tension pneumothorax or cardiac tamponade (obstructive shock).
      Volume resuscitation by means of crystalloid or colloid solutions is an essential
      part in the therapy of the traumatic-haemorrhagic shock. In addition,
      catecholamines may be necessary in order to achieve an adequate arterial
      pressure. However, if bleeding cannot be controlled in the prehospital setting,
      only moderate volume support and permissive hypotension as well as rapid
      transportation into the next hospital may be preferable. This may be the case in
      penetrating thoracic or abdominal injuries as well as in traumatic amputations of
      the proximal limb. On the contrary, in patients with severe head injury,
      hypotension must be avoided by all means. Obstructive shock has to be treated
      urgently by insertion of a chest drain or drainage of the pericardium,
      respectively. Under all circumstances, it is an essential part of prehospital
      therapy to provide sufficient analgesia as soon as possible. Prehospital
      anesthesia, combined with artificial ventilation may be necessary for optimal
      patient management. Furthermore, ventilatory support is indicated when
      respiratory failure, loss of consciousness, or severe shock are present.
      Additional oxygen should be given whenever possible, even in the absence of an
      overt hypoxic state. Important additional measures are cervical spine
      immobilisation and reposition as well as splinting of long bone fractures or
      luxations, in order to avoid secondary injury of the spinal cord or ongoing
      tissue and vascular damage.

PMID- 9027152
TI  - [Intensive care medicine aspects of polytrauma].
AB  - Multiple trauma often leads to systemic inflammatory reaction and multiple organ
      dysfunction. Modulation of this response may be promising. Several pharmacologic
      approaches, such as antioxidants (e.g. superoxidedismutase), calcium channel
      blockers (e.g. diltiazem), cytokines (e.g. interferone gamma), and modulators of
      intracellular signal transduction pathways (e.g. pentoxiphylline) have been shown
      to improve outcome in experimental models and/or in clinical pilot studies.
      However, up to now no definitive evidence has been provided in prospective,
      randomized, and blinded "intention to treat" trials that these agents are able to
      reduce mortality and morbidity of the traumatized patient. Hence, supportive care
      of failing organs, treatment of hypoxemia and maintenance of an appropriate
      systemic blood pressure remain the mainstay of critical care therapy. Widely
      accepted therapeutic measures are (i) immediate treatment of hypoxia by
      administration of oxygen and ventilatory support, if needed, to maintain an
      oxygen tension of 60 mmHg or higher (ii) maintenance of adequate oxygen content
      by transfusion of red packed cells in order to restore a hematocrit of 23-30%
      (iii) treatment of hypovolemia by infusion of crystalloids, colloids and blood
      products (iv) normoventilation and restoration of a normal or elevated blood
      pressure in patients with severe head injury (v) immobilisation and early
      administration of methylprednisolone in patients with spinal cord injury (vi)
      analgesia by administration of opioids, non-steroidal antiinflammatory drugs, or
      ketamine (vii) sedation with benzodiazepines, gamma-hydroxbutyrate or propofol
      (viii) early enteral nutrition (ix); antibiotic therapy of infections (x)
      pressure controlled ventilation in patients with acute lung injury (xi)
      continuous veno-venous hemofiltration in patients developing acute renal failure
      and (xii) early surgical interventions to control bleeding and/or to evacuate
      intracerebral hematomas.

PMID- 9027151
TI  - [Strategy of surgical management of polytrauma].
AB  - Operative procedures in multiple injured patients consist in the first stage in
      life-saving operations such as control of bleeding and cerebral decompression.
      Operative measures during the urgent second operative phase have to be undertaken
      under consideration of the development of a multiple organ failure syndrome.
      Early stabilization of relevant extremity fractures and thorough care of soft
      tissue are of particular importance (day-1-surgery). Only second look procedures
      to optimize soft-tissue injuries and prevent infections may be allowed during
      this early intensive care period. Delayed operative procedures should only be
      performed after stabilization of the overall patient situation to prevent
      enhancement of the systemic inflammatory response. The required operative
      procedures of the multiple injuries have to be attributed to the respective
      operative phases.

PMID- 9027153
TI  - [Perspectives of polytrauma management].
AB  - Despite a high standard of preclinical, clinical and rehabilitative trauma care,
      the number and degree of injuries will remain a social and medical challenge.
      Improvements of trauma care in the future may be possible in respect to social,
      economic, organisational, clinical and research issues. Prevention of trauma will
      be of major impact and improvements may be possible by preventive legislation and
      technical developments. Organisation of trauma care should integrate high level
      trauma centres early-on including a national, regional and local quality control
      system. The future preclinical and clinical individual care of multiple trauma
      patients should consider the complex pathophysiological mechanisms at all levels,
      while the understanding of these mechanisms is increasing continuously.

PMID- 9027154
TI  - [Primary traumatic midbrain syndrome--follow-up and prognosis of acute primary
      brain stem damage].
AB  - Within 27 months 122 patients with severe head injury were treated at our clinic.
      Of these patients twelve (9.8%) were categorized as having a primary brain stem
      lesion (9 male and 3 female, mean age 28.3 years (17 to 73 years). Their injuries
      were caused primarily by traffic accidents. Initial and follow-up CT ruled out
      mass lesions or other causes for transtentorial herniation, supporting the
      diagnosis of primary brain stem lesion. Respiratory insufficiency and control of
      vegetative function demanded artificial ventilation and analog-sedation for up to
      32 days (mean 18 days) on our Intensive Care Unit. In all patients we performed
      initial and follow-up CT scans, ICP monitoring, evoked potentials (AEP, SSEP) and
      TCD. MRI was carried out in four patients. One patient died during the acute
      hospital phase, 7 were transferred in poor and four in good condition. During
      rehabilitation one patient died, two, one in a vegetative state and one in poor
      condition were transferred to a caring facility. Eight patients with a good or
      moderate recovery were dismissed home, subsequently regaining their prior social
      function. The primary traumatic brain stem lesion presents as a dramatic clinical
      picture. As shown in our series the prognosis is good independent of the duration
      of coma. The important prognostic factors were the primary neurological state
      according to the Gerstenbrand and Luecking classification, the degree of the
      brain stem lesion in CT scan and MRI, and normal evoked potentials, indicating a
      favourable outcome.

PMID- 9027155
TI  - [Treatment concept and results of grade 3 open fractures with arterial injuries
      requiring reconstruction].
AB  - Ninety-one open fractures associated with arterial injury requiring vascular
      repair (type IIIC injuries) were treated at the University of Louisville between
      May 1983 and January 1994. Involved anatomical areas were the humerus (6x), the
      forearm (11x), the femur (16x), the tibia (36x), the ankle (11x) and the foot
      (11x). Fracture management consisted of meticulous radical debridement, copious
      wound irrigation, fasciotomy and fracture stabilization. Additionally, 49 wounds
      (53.8%) were treated with the supplemental local use of antibiotics (tobramycin
      PMMA-beads). Thirty-four patients underwent primary amputation whereas 57 repairs
      of the injured vessels were performed. There were 7 secondary amputations due to
      infection or poor revascularization resulting in an overall amputation rate of
      45.1%. The wound infection rate was 12.1% (11/91) and the rate for osteomyelitis
      was 3.3% (3/91). The local use of the antibiotic beads was of significant benefit
      to lower infectious complications. Primary coverage of the soft tissue defect
      with free tissue transfer was associated with a high infection rate (2/3) and is
      not recommended for this type of injury. Temporary wound coverage with the
      "antibiotic bead pouch" technique until wound closure can be obtained in a
      sterile and viable environment leads to more satisfying results.

PMID- 9027156
TI  - [Surgical management of bone metastases of the lower extremity with AO
      interlocking nail].
AB  - Between January 1991 and June 1995 we have operated on 19 patients (9 male, 10
      female) with 22 skeletal metastases of the lower limb (19 femora, 3 tibiae) using
      a static interlocking nail. Closed intramedullary nailing without resection of
      the metastasis has been established as our standard procedure. We have stabilized
      15 patients with advanced osteolysis and seven pathological fractures. Sixteen
      patients underwent postoperative local radiation therapy with 40 Gy. As
      intraoperative complications we have observed one fracture of an osteolysis and
      one death due to fat embolism. Postoperatively there were observed one seroma,
      one haematoma and one patient with non fatal pulmonary embolism following DVT.
      Two patients died within the first 30 postoperative days because of tumor
      progression. All patients surviving longer than 30 days could be mobilized under
      full weight-bearing. Morphine like analgetics for metastasis related pain were no
      longer needed. A secondary instability has not been observed within a mean
      survival time of 199 days (811 longest follow up). Closed intramedullary nailing
      in combination with postoperative local radiation therapy seems to be an
      appropriate and technically non demanding procedure to stabilize skeletal
      metastases of the lower limb in patients with a short or medium-term expectation
      of life.

PMID- 9027157
TI  - [Ixodid tick-borne borrelioses--a new group of human diseases].

PMID- 9027158
TI  - [The virulence of enterobacteria and immunity].

PMID- 9027159
TI  - [An analysis of the stability of the antigenic structure in productive strain 205
      of the tick-borne encephalitis virus during prolonged passage].
AB  - The stability of the antigenic structure of tick-borne encephalitis (TBE) virus
      strain 205 in the process of passage through the brain of BALB/c mice has been
      studied. Its relationships with other viruses of the TBE complex have been
      analyzed with the use of monoclonal antibodies to virus proteins E and NS3. The
      stability of the protein structure of the virus has been determined by the
      immunofluorescence test and the enzyme immunoassay.

PMID- 9027160
TI  - [150 years of discussions on the reservoir of the causative agent of cholera and
      the mechanisms of human infection].

PMID- 9027161
TI  - [The epidemiological characteristics of a cholera outbreak in the Crimea].

PMID- 9027162
TI  - [The basic principles in organizing a laboratory service in a cholera focus].

PMID- 9027163
TI  - [An outbreak of food poisoning at a children's rest base].

PMID- 9027164
TI  - [Food poisoning in a boarding school].

PMID- 9027165
TI  - [The 70th anniversary of the Khabarovsk Research Institute of Epidemiology and
      Microbiology].

PMID- 9027166
TI  - [The stimulating action of exogenous RNase on eubiotic strains of Lactobacillus,
      Bifidobacterium and Escherichia coli].
AB  - The influence of Bacillus intermedius RNAase on the multiplication on
      B.B.bifidum, L.fermentum and E. coli was studied. The study revealed that the
      stimulating action depended on the dose of the enzyme, the microbial species and
      the growth phase of the inoculate. RNAase, added to the nutrient medium, was
      shown to induce the acceleration of the synthesis of DNA, RNA, protein, as well
      as mitosis. At the same time the stimulating action of RNAase was accompanied not
      only by the reduction of the duration of the lag phase, but in some cases even by
      an increase in the specific growth rate.

PMID- 9027167
TI  - [The characterization of Francisella tularensis mutants and subspecies by using
      monoclonal antibodies].
AB  - Monoclonal antibodies to F.tularensis cells, subspecies holarctica, were studied
      for the capacity of reacting with F.tularensis, subspecies nearctica, and its
      mutants having lower virulence and altered capacity for inducing protective
      immunity to tularemia in laboratory animals. Among the antibody-producing
      hybridoma clones under study, clones F8/67 and C7/65 capable of distinguishing
      the mutants of F.tularensis, subspecies nearctica, with lower virulence than that
      of the initial strain were selected. Antibodies of these hybridoma clones did not
      interact with the antigens of the initial virulent strains of F.tularensis,
      subspecies nearctica, while giving pronounced reaction with the antigens of its
      mutants. Close F8/67 produced IgG antibodies and clone C7/65, IgM antibodies. As
      shown in immunoblotting, antibodies produced by these hybridoma clones bound with
      proteins of F.tularensis cell membranes.

PMID- 9027168
TI  - [The variability of the biological characteristics of Vibrio cholerae isolated
      from environmental objects].
AB  - The study of the biological characteristics used for the identification of the
      species, biovar and serovar of V.cholerae O1 isolated from environmental objects
      on the territory of 8 regions of Ukraine for the period of 1974-1993 revealed the
      tendency towards an increase in the number of altered cultures. Phage sensitivity
      (60.7%) and capacity for agglutination with cholera species- and type-specific
      sera (24.6%) proved to be the most variable properties. Resistance to polymyxin
      (4.8%), the absence of hemagglutination with chick red blood cells (8.7%), the
      absence of diastatic activity (28.9%) were also detected. The study established
      that the temporal, ecosystemic and territorial geographical dependence could be
      observed in the character of variability of V.cholerae O1. The data thus obtained
      indicate the expediency of monitoring the dynamics of the properties of
      V.cholerae O1 in order to establish the relationship between its variability and
      the epidemic process.

PMID- 9027169
TI  - [The development of a Proteus mirabilis macrocolony on a solid nutrient medium].
AB  - As revealed in this study, the macrocolony of Proteus mirabilis, formed on solid
      culture medium, may consist both of the main part and of sporadically appearing
      dissociating subcolonies, considerably differing one from another. The outer edge
      of the main part of the macrocolony of swarming cells is represented by bacteria
      located in three perpendicular directions. The next intermediate area consisting
      of two layers is represented by bacteria oriented, as a rule, in one direction.
      The center of the colony is made up of short microbial cells. Between the upper
      layer and the surface of agar an original subpopulation of microbial cells,
      forming a separate layer, has been detected; together they determine the planar
      sandwich-like architectonics of the macrocolony.

PMID- 9027170
TI  - [The adhesive activity of Klebsiella pneumoniae controlled by plasmid 55 MD].
AB  - In K. pneumoniae clinical strains a nonconjugative plasmid, denoted as pAdh-55
      and responsible for their adhesive activity with respect to HEp-2 cells, was
      detected. The comparison of genetically related pairs of K. pneumoniae strains
      differing in the presence of pAdh-55 revealed that the loss of this plasmid by
      bacteria was accompanied by a decrease, and its acquisition by a considerable
      increase, in the number of Klebsiella-affected cells in the monolayer. The
      correlation between the presence of pAdh-55 in K. pneumoniae strains and their
      adhesive activity was established both in experiments aimed at the morphological
      study of preparations stained with azure eosin and in experiments with isotope
      labeled bacteria.

PMID- 9027171
TI  - [The taxonomic importance of the capacity of bacteria in the genus Staphylococcus
      for the inactivation of a number of natural anti-infectious resistance factors].
AB  - Bacteria of the species S. aureus are characterized by a wide range of signs
      indicating the inactivation of natural resistance factors, including
      anticomplement activity, which makes them different from coagulase-negative
      staphylococci exhibiting only antilysozyme activity. The taxonomic importance of
      these tests and their possible use for the identification of staphylococcal
      species are discussed.

PMID- 9027172
TI  - [The pathogenetic and clinico-diagnostic significance of changes in leukocyte
      migration activity in patients with shigellosis and salmonellosis].
AB  - The peripheral blood leukocyte migration activity (LMA) was studied in 134 acute
      dysentery patients and 129 salmonellosis patients by using the in vitro screening
      assay of cell migration (SACM) from microcultures, stimulated with LPS antigens
      from a number of enteric pathogens. At the acute period of the disease (days 1-5)
      in the greater part of the patients (80-90%) the specific acceleration of LMA,
      later followed by its inhibition, was registered in the presence of the
      pronounced intoxication and diarrhea syndromes, as well as the intensive
      circulation of specific antigens of the infective agents in the body (established
      by the method of the coagglutination test). The established phase fluctuations of
      LMA correlated with the severity and character of the infectious process. SACM
      was found to be highly sensitive and specific, convenient, well reproducible and
      having good prospects for the early diagnosis of enteric infections, including
      those of mixed etiology.

PMID- 9027173
TI  - [A DNA analysis of Vibrio cholerae strains by the polymerase chain reaction].
AB  - The method for the analysis of cholera toxin gene in V. cholerae strains was
      developed on the basis of polymerase chain reaction (PCR). This specific and
      highly sensitive method using primers affecting the site of the DNA of the operon
      of cholera toxin gene made it possible to identify one copy of V. cholerae
      genome. For the first time the content of cholera toxin gene in 4 V. cholerae
      (eltor) strains, obtained from the clinical material of cholera patients in
      Tajikistan and Dagestan, was shown with the use of PCR.

PMID- 9027174
TI  - [Problems in and the means for improving the epidemiological surveillance of HIV
      infection].
AB  - The system of the epidemiological surveillance of HIV infection, existing now in
      Russia and aimed at the detection of sources of the infective agent, is not
      adapted for territories with a low level of HIV infection among the population.
      This makes it impossible to evaluate the factors which may contribute to the
      epidemic spread of the infective agent. A new program of epidemiological
      surveillance is proposed. This program is based on the complex approach to
      monitoring infections having epidemiological signs, common with HIV infection; on
      the organization of serological monitoring for the detection of HIV-seropositive
      persons on the basis of blind tests and orientation on monitoring the social
      factors which determine the spread of HIV infection.

PMID- 9027175
TI  - [Salmonellosis in Moscow: its epidemiological characteristics and the prevention
      tasks].
AB  - Zooanthroponotic Salmonella infections in Moscow are characterized, on the whole,
      by the same epidemiological characteristics as in other areas of Russia. Despite
      the pronounced polyetiological character of these infections, only a few
      Salmonella serovars were found to dominate in their dynamics for many years. The
      1970s were characterized by a growth in morbidity due to a wide spread of
      S.typhimurium among children of early age in hospitals. This situation was
      stabilized by 1985, but since 1986 a sharp rise in morbidity was observed again,
      reaching its peak in 1989. This time its rise was determined by S.enteritidis,
      whose specific etiological importance grew from 13.3% to 81.3%. The growth of
      these bacteria was determined by a sharp increase in the epidemic role of such
      transmitter factors of Salmonella infection as chicken meat, prepared chicken
      meat products, as well as chicken eggs and their products, including
      confectionery, which production appreciably increased during this period
      simultaneously with the presence of a high level of infection among poultry in
      Russia with salmonellae of this serovar. High morbidity, observed all year round,
      with a high proportion of adults among patients (more than 60%) is the direct
      consequence of the preserved still present epidemic activity of the "chicken"
      factor and a high virulence of S.enteritidis.

PMID- 9027176
TI  - [The epidemiological characteristics of Sonne and Flexner dysentery in St.
      Petersburg in 1953-1994].
AB  - In connection with the growth of mortality in Flexner's dysentery observed since
      1991 and a rise in morbidity in this infection since 1993 the data on the
      registered cases of Shigella flexneri and Shigella sonnei infections in St.
      Petersburg for the period of 1953-1994 were analyzed. In the 60-80s the specific
      features of the epidemic process was determined by S. sonnei infection which
      constituted up to 90% of all documented cases of dysentery. Flexner's dysentery
      lost the character of a mass epidemic disease in the 60s, but in the 70s became
      again capable of epidemic spread, which was testified by annual seasonal rises
      producing a half of all cases registered per annum and two rises with peaks in
      1975 and 1984. In 1991-1992 the tenfold rise of morbidity in Flexner's dysentery
      took place in the presence of a common level of morbidity of Shigella infections.
      In 1993-1994 an essential change in the etiological structures of Shigella
      infections was observed: morbidity in Flexner's dysentery rose 6 times and
      morbidity in Sonne dysentery dropped 3 times, which was probably due to socio
      economical changes in the living conditions of the population during recent
      years.

PMID- 9027177
TI  - [Epidemiological data on salmonellosis due to Salmonella enteritidis in some
      areas of the Russian Federation].
AB  - A rise in morbidity caused by S. enteritidis at individual territories of the
      Russian Federation in the second half of 1980s was due to the consumption of
      insufficiently heated infected chicken eggs and the nonobservance of sanitary and
      hygienic rules in the preparation of food from chicken meat. The spread of S.
      enteritidis in the Russian Federation occurred mainly at the territories supplied
      with incubator eggs from the same poultry-breeding enterprise. S. enteritidis
      strains isolated from infected patients, chicken eggs, follicles and chicken-meat
      products belonged to biovar Jena (as a rule, to phagovar 1), had plasmid with a
      mol. wt. of 38 MD, produced no aerobactin, and their overwhelming majority was
      resistant to antibiotics.

PMID- 9027178
TI  - [An analysis of the epidemic cycle of meningococcal infection in Russia (1969
      1993)].
AB  - In this work the specific features of the epidemiological rise of morbidity in
      meningococcal infection in Russia for the period of 25 years are analyzed. Some
      factors influencing the intensity of the disease, such as etiology, specific
      features arising from the age of patients, social and territorial factors, are
      analyzed. Two waves of epidemic have been established in a single epidemic cycle.
      The first wave of epidemic was caused by meningococci of group A and
      characterized by the prevalence of city-dwellers among the patients; the second
      wave was caused by meningococci of groups A and B with the prevalence of the
      latter, especially during the period of the slump of the wave. The "Asiatic" and
      "European" types of morbidity were distinguished (in Moscow and St. Petersburg).
      The analysis of the epidemic cycle of meningococcal infection indicates the
      expediency of the development of new specific wide-profile preparation for
      prophylaxis.

PMID- 9027179
TI  - [The biotype and genetic characteristics of an isolate of the cowpox virus
      causing infection in a child].
AB  - A virus, identified as cowpox virus by its biological properties and the results
      of the analysis of its DNA, was isolated from a sick 4-year-old child with a
      clinical picture of pox, though having had no contacts with known natural
      carriers of the causative agent of this infection. At the same time the isolated
      virus was found to differ from the reference strain, as well as from other
      isolates of vaccinia virus by some biological markers (and in particular by the
      structure of cytoplasmic inclusions of type A) and by the restriction profile of
      DNA. The Hind III maps indicating the location of restriction sites made it
      possible to localize the genome differences established in this study. The
      specific feature of this case was the previous close contact of the child with a
      mole which was probably the source of infection.

PMID- 9027180
TI  - [The results and prospects for the vaccinal prophylaxis of mumps in Russia].
AB  - In recent years the rise of morbidity in epidemic parotitis (EP) has been
      observed in our country, which determines the development of major outbreaks and
      further increase in EP morbidity due to the regular accumulation of a
      considerable number of susceptible persons among the vaccinees. This is mainly
      caused by low immunogenic potency of live parotitis vaccine produced in Russia
      and the insufficient content of the virus in a vaccination dose. A definite
      contribution is also made by the insufficient coverage of the population with
      vaccination, low efficiency of vaccination made in a single injection and the
      absence of the quality control of the vaccine in individual regions. Only the
      complex solution of these problems will lead to the liquidation of EP in the
      country.

PMID- 9027181
TI  - [The lymphocyte phenotype of patients with different forms of diphtheritic
      infection and of bacterial carriers].
AB  - The subpopulation composition of lymphocytes in patients with different forms of
      diphtheria infection before treatment was studied by the method of laser
      cytometry with the use of monoclonal antibodies. Statistically significant
      differences in the characteristics of cell-mediated immunity between groups of
      diphtheria patients and carriers were obtained. In cases of diphtheria with
      different degrees of severity an essential decrease in the content of T
      lymphocytes and B-lymphocytes was established. The most prolonged changes
      affected cells carrying differentiating antigens CD3, CD4, CD8, CD72. Their
      number increased by day 5 of the disease, while the number of activated cells
      (CD21 and HLA-DR) progressively decreased. The correlation between the gravity of
      the course of diphtheria infection and the state of T-cell-mediated immunity was
      established.

PMID- 9027182
TI  - [An immunomodifier--staphylococcal anatoxin--prevents the development of
      immunosuppression caused by informational stress in mice].
AB  - The action of information stress for 14 days leads to the development of
      immunosuppression, which is manifested by the suppression of humoral response to
      sheep red blood cells (SRBC) and the decrease of resistance to Langat virus
      having low pathogenicity. As shown in this investigation, an immunomodifier,
      purified staphylococcal toxoid (PST), protects experimental animals from the
      immunosuppressive effect of information stress. After the injection of PST to
      stress-affected mice in doses of 15 or 1.5 binding units per animal on days 9, 11
      and 13 of the experiment their humoral response to SRBC and resistance to Langat
      virus are partially restored (by 45-60%).

PMID- 9027183
TI  - [The immunogenicity and heterogeneity of Pseudomonas pseudomallei surface antigen
      8].
AB  - Surface antigen 8, one of pathogenicity factors of P.pseudomallei and having an
      antiphagocytic action, contains glycoprotein with a mol. wt. of 200 kD and
      proteins with mol wt. of 25, 30 and 34 kD. According to its chemical structure,
      the carbohydrate part of antigen 8 is the homogeneous polymer of 6-d-D
      mannoheptose, and its protein component is a collection of monomer proteins with
      mol. wt. of 12-120 kD. The consecutive fractionation of antigen 8 by gel and ion
      exchange chromatography has made it possible to isolate its individual fragments,
      differing by the collection of antigenic components, as well as by their
      antiphagocytic and protective activity. Experiments have shown that glycoprotein
      with a mol. wt. of 200 kD is an active immunosuppressive agent, while protein
      with a mol. wt. of 34 kD produces a pronounced immunogenic effect.

PMID- 9027184
TI  - [Environmental pollution and the characteristics of the epidemic process in
      diphtheria].
AB  - The analysis of materials for 1981-1993 on the city of Almaty and the Zhambyl,
      Aktyubinsk, East Kazakhstan and Kustanai provinces of the Republic of Kazakhstan
      made it possible to find out a number of specific features in diphtheria
      morbidity under the conditions of environmental pollution. It caused an increase
      in the number of the foci of the disease and in the proportion of bacterial
      carriers and diphtheria patients in the foci, the growth of the proportion of
      children among the patients and the proportion of toxic forms of diphtheria, the
      tendency towards a rise in the frequency of unfavorable outcomes of the disease.
      These features correspond to earlier data on the decreased immunological
      effectiveness of immunization with adsorbed DPT vaccine in the presence of
      environmental pollution in the above-mentioned territories.

PMID- 9027185
TI  - [The problem of designing typhoid vaccines].

PMID- 9027186
TI  - [Hepatitis E].

PMID- 9027187
TI  - [The molecular epidemiology of typhoid].

PMID- 9027188
TI  - [Rochalimaea and its role in human pathology].

PMID- 9027190
TI  - [Malignant mitral valve prolapse: apropos of a case].
AB  - The authors report the case of a 67-year-old woman, with mitral valve prolapse,
      for more than 20 years. She recently complained of attacks of syncope and
      clinical ventricular tachycardia; ventricular fibrillation was induced during
      programmed stimulation. The patient seemed to be at high risk for sudden cardiac
      death, and was therefore treated with an automatic implantable defibrillator. The
      pathophysiology and risk factors of sudden cardiac death in mitral valve prolapse
      are discussed.

PMID- 9027189
TI  - [Methods in surgical antibacterial prophylaxis in Belgium, 1992-1995].
AB  - Since 1992, the Belgian network for the surveillance of nosocomial infections
      runs a system of voluntary surveillance of surgical wound infections, including
      the perioperative antibiotic prophylaxis patterns. From 1992 to 1995, the global
      rate of prophylaxis was 71%, calculated on 44,728 interventions from 72
      hospitals, but in 11.4% of operations for which prophylaxis is indicated, it was
      not given. On the other hand, prophylaxis was prescribed in 55.6% of operations
      where it was not indicated. At least 4 out of 10 courses were inappropriate with
      respect to indication, duration or day of administration. Fifteen percent of all
      courses exceeded 2 days (28% in genitourinary surgery, and 20% in abdominal
      surgery). In orthopedic surgery, recommended indications were not followed in 42%
      of operations. To improve the prescribing of antibiotic prophylaxis in Belgium,
      local surveillance of prophylaxis patterns and the implementation of guidelines
      describing good practices should be priorities at the hospital level. At the
      national level, recommendations about the indications for prophylaxis should be
      updated and disseminated.

PMID- 9027191
TI  - [Sleeping sickness as an import pathology following a stay in Zaire].
AB  - A 32-year-old Italian man developed fever and general malaise 3 weeks after
      arrival in Zaire. Malaria was diagnosed by a thick blood film, but consequent
      treatment with quinine was unsuccessful. After repatriation, the diagnosis of
      early stage sleeping sickness was established. Treatment with eflornithine
      (Ornidyl) resulted in complete recovery.

PMID- 9027192
TI  - 20 Years' advances in otolaryngology--head and neck surgery. Commemoration of the
      20th anniversary of Professor Shunkichi Baba taking his post at the Department of
      Otolaryngology, Nagoya City University Medical School.

PMID- 9027193
TI  - [The evolution of the techniques used to correct nasal septum function].
AB  - At the dawn of rhinosurgery, the otolaryngologist operated on the nasal septum
      while a plastic surgeon handled treatment of the "noble" portion of the nose,
      i.e. the nasal pyramid. However, the plastic surgeon dealt more with esthetics
      than with function. Discussion and doubts revolved around the priorities of
      septum vs. pyramid treatment. Such doubts have often gone unresolved and has led
      to an unusual dichotomy in nasal surgery: the break down into septoplasty and
      rhinoplasty. This scission has fallen by the wayside during the course of the
      years. Indeed, today, where necessary, one tends associate corrective rhinoplasty
      during the course of septal procedures. During this historical review of
      functional surgery of the nasal septum, some mention is made of the numerous
      techniques and variations thereof which have been presented by various authors.

PMID- 9027194
TI  - [The history of nasal valve surgery].
AB  - Nasal valve surgery involves the Nasal Valve Area and its deformities, as well as
      its surrounding structures. Since there is no single technique to solve every
      type of pathology, there are numerous works on this topic in the literature. The
      rhinologist to perform such surgery should thoroughly deal with all the
      components (i.e. nasal valve area, nasal bones, tip, spine, vestibulum and
      turbinates). However, even more so, he should be able to precisely locate the
      cartilaginous and/or osseous structural deformity impairing nasal air flow.
      Therefore, intuition and experience play a key role in planning such surgery. It
      is not easy to recognize the unique, or even more difficult, the partial defect
      the correction of which would improve overall nasal function. Every surgical
      technique has some "biologic cost": sclerosis, adhesions, and scar retraction.
      However, in this case the surgery could prove even more biologically costly as it
      could worsen the already poor nasal breathing. Therefore, the surgeon must
      strictly follow two basic rules: a) employ a proper approach to the region; b) do
      not endanger nasal valve function to satisfy esthetics. Valve area anomalies can
      be divided into primary and secondary. The latter are caused by trauma or surgery
      (1.2%). Among the wide range of techniques mentioned in the literature, the
      authors prefer the anatomical, surgical classification by Zijilker and
      Quaedvilieg as it incorporates the philosophy the rhinosurgeon must keep in mind
      when aiming to restore both nasal functions and esthetics through different,
      specific techniques.

PMID- 9027195
TI  - [Presumed physiopathology of the nasal wall surgery and contemporary techniques
      of the inferior turbinates surgery].
AB  - The lateral wall of the nasal cavity is anatomically complex and covers several
      nasal functions: ventilation, conditioning of the air, protection. This region
      also plays a prime role in maintaining nasal-sinus homeostasis through dynamic
      regulation of the two-way exchange between the nasal cavity and paranasal
      sinuses. In light of the most recently acquired information, physio-pathological
      aspect of the lateral wall are discussed in terms of ventilation mechanisms and
      mucociliary clearance of the paranasal sinuses. In this light, the key to nasal
      sinus physiology is clearly the perviousness of the side wall ostium and, above
      all, the status of the structures making up the "ostiomeatal complex". The
      anatomo-functional integrity of the lateral wall is fundamental for sinus
      ventilation 90% of which depends on passive diffusion of air through ostium. It
      is also a key to mucociliary clearance, always directed toward the main ostium.
      This rationale provides the basis for the so-called functional surgery of the
      lateral wall aimed at restoring ostium permeability. One structure in the lateral
      wall is a key to nasal physiology: the lower turbinate. Anatomical or functional
      alterations of the lower turbinate is one of the major causes of nasal stenosis.
      Pharmacological treatment of this pathologies is not always satisfactory, hence
      one leans toward surgical treatments. Nevertheless, the wide range of techniques
      available attests to the fact that there is still great deal of uncertainty in
      this regard. After having analysed the data available in the literature, the
      authors propose a comparison of some of the most frequently used forms of
      surgery: electrocauterization, cryotherapy, laser therapy, submucosal
      decongestion with or without luxation, turbinectomy. Follow-up based on
      rhinomanometric evaluation, rhinometry, TTMC, IgA assay and symptom scoring has
      been performed for 4 years. The results show that the submucosal decongestion
      technique, particularly the variation with lateral luxation, is considered most
      effective in resolving obstruction while respecting nasal physiology.

PMID- 9027196
TI  - [Modern corrective nasoseptal surgery].
AB  - Inner nose surgery should be addressed to normalize the geometry of the nasal
      cavities in order to restore physiologic nasal resistance. As the nasal septum
      plays a key role in the form and the function of the nose, a successful
      rhinosurgeon must be able to deal with all septal problems ranging from localized
      spurs to severely traumatized or surgically damaged nasal septa. Nasal airway
      obstruction due to septal derangements cannot be successfully solved simply by
      submucous resections of septal window(s) but does often require a range of
      corrective maneuvers on the anatomic sub-units constituting the septum. Septal
      surgery is systematically performed by the Authors using the maxilla-premaxilla
      approach (MPA) which allows access to and manipulation of the entire nasal septum
      including the caudal and anterior septal margins, columella, upper lateral
      cartilages, inferior nasal spine as well as floor of the nasal cavities and
      maxillary crest areas. Correction of the septum combines mobilization and/or
      removal of any deranged portion of the bony and/or cartilaginous septum, followed
      by reconstruction of the septum support, preferably using autogenous septal
      grafts. Reconstruction procedures are designed to reconstitute a stable medial
      wall and at the same time minimize scar tissue formation. Reconstruction is
      indispensable to avoid septal flapping occurring when the medial wall consists of
      muco-periosteal tissue only without firm intermediary support. When
      reconstructing the medial wall, great care must be taken with the most important
      portion of the septum, i.e. the dorso-caudal margin and the cartilaginous
      elements. However, many common nasal problems require procedures to correct the
      inside of the nose and the external pyramid at the same time. To effectively and
      efficiently address the challenge posed by the combination of internal and
      external nasal problems, a thorough understanding of respiratory rhinology as
      well a familiarity with the many procedures involved in both extensive septal
      surgery and external nasal pyramid surgery are imperative for the modern-day
      rhinosurgeon.

PMID- 9027197
TI  - [The history and evolution of the surgical techniques in rhinoplasty].
AB  - Few other forms of surgery embody the authentic, full essence of surgery as does
      rhinoplasty, where functional results are joined to meet one's innermost
      expectations. the present work reviews the main stages in the course of the
      evolution of the philosophy and surgical techniques adopted to resolve both the
      functional and esthetic problems of the nose. This provides a broad view of the
      issues every surgeon has had to deal with in this regard. The history of
      rhinoplasty once more teaches us that the evolution of a discipline hinges around
      the daily renewal of one's preparation through study, observation and insights.

PMID- 9027198
TI  - [Septorhinoplasty in childhood].
AB  - Septorhinoplasty plays an important role in childhood, particularly from the
      functional point of view. In fact, normal nasal respiration makes it possible to
      develop physical harmony throughout the entire body, particularly within the
      facial area. Nasal respiration serves as a defense mechanism, filtering air, thus
      relieving the lower respiratory tract of some work during the episodes of upper
      aero-digestive tract infection and inflammation so typical of childhood and early
      adolescence. The surgical indications should consider the central points in nasal
      surgery in childhood: there must be marked functional compromise; the aesthetic
      defect, if present, must be highly evident; the surgical treatment must be as
      limited and focused as possible as to prevent interfering with subsequent
      development of the nose, paranasal sinuses and facial structures. In those cases
      where the above conditions are not found, it is advisable to postpone surgery
      until the child has reached 16 years of age, when the development of the nasal
      and facial skeleton has been completed.

PMID- 9027199
TI  - [The actual problems in functional and aesthetic nasal surgery].
AB  - Functional and aesthetic nasal surgery has been undergoing a process of fine
      tuning. The surgical approaches lean toward greater conservation-particularly
      aesthetic- and functional selectivity. This has been made possible by improved
      diagnostic methods and pre-operative programming techniques such as computerized
      morphometry, computerized axial tomography, rhinosinus endoscopy, rhinomanometry,
      acoustic rhinometry and electromyography. Another important point in functional
      and aesthetic nasal surgery is that a) it can be divided into different
      techniques for each anatomo-functional sector considered and b) these can be used
      together in various combinations. Experience and the literature have underscored
      some issues which are most pertinent to the modern methodological viewpoint. The
      first large-scale controversy involves a comparison of open and closed techniques
      for access. The advantages and disadvantages of both techniques are described,
      although the disadvantages can be reduced to a minimum if the right indication is
      chosen. In the authors' opinion, the open technique should be reserved for
      general revision surgery, particularly in conjunction with difficult tips,
      labiopalatoschisis reconstruction, septal perforation and saddle nose. The second
      basic point involves how to deal with the perichondrium-periostium-mucosal flaps.
      The two main techniques for nasal skeletizing in rhinoseptoplasty include the
      extra-mucosal approach which is conservative and the trans-mucosal approach which
      is apparently more traumatic. Curiously, however, it is the latter technique
      which leads to fewer medium-long term complications. The nasal tip is the crux
      for the neophyte to rhinoseptoplasty. Through knowledge of the indications and
      the risks of the various techniques makes it possible to predict the result
      before-hand, although with certain margin of error. Indeed, this is one of the
      regions of the nose where errors reap the greatest damage. In this anatomical
      site, the use of conservative techniques is, therefore, strongly suggested.
      Finally, not only has research into the field of functional nasal surgery been
      unable to find concrete applications in humans (for obvious ethical reasons), it
      has likewise been unable to provide an answer to the question most rhinosurgeons
      pose: why do some patients still complain of difficulty breathing, even after
      successful surgery? It is our conviction that the problem is due to the fact that
      research into the endonasal receptors has not progressed.

PMID- 9027200
TI  - [Cartilaginous grafts in primary rhinoplasty].
AB  - In staging and performing secondary iatrogenous or post-traumatic rhinoplasty, it
      has clearly been shown that the use of grafts plays a key role in reconstructing
      the defective or missing anatomical parts. On the other hand, in primary
      rhinoplasty, in general the one prevailing concept is removal of the osteo
      cartilage to shape the nose. However, in order to achieve a good balance between
      aesthetics of the various parts of the nasal pyramid and their coherence with the
      face as a whole, it is often necessary to add at one or more points so that you
      can remove less elsewhere. In effect, a naturally short nasal tip, unless
      suitably increased, would require marked removal of the gibbus which could, in
      turn, throw the nasal pyramid out of proportion with the rest of the face. On the
      other hand, if the back of the nose is naturally too short, it creates the
      optical illusion of a tip which is longer than it really is. This also holds true
      for a tight nose-lip angle or when the portion of the face anterior to the upper
      jaw is set back, creating the optical illusion of a downward or elongated tip.
      Integrating the back of the nose, the anterior nasal spine or the canine fossae
      with a graft makes it possible to achieve more natural results in harmony with
      the rest of the face. The material of choice for the grafts used by the authors
      is the quadrangular cartilage of the nasal septum, both autologous and
      homologous. This material is preserved in a aqueous solution of 10% mertiolate.
      An alternative can be provided by the cartilage of the auricular concha.

PMID- 9027201
TI  - [8-year experience with force vector rhinoplasty by J.B. Tebbetts: comparative
      results].
AB  - The aim of the present work is to make a contribution in resolving the
      controversy between the traditional and "open" approaches to rhinoseptoplasty.
      Over these last few years, particularly in the United States, the Rethi technique
      (1920) has encountered unceasing opposition among those using the "open" approach
      and those who, on the other hand, assert that they can achieve equivalent results
      without resorting to the supplementary columellar incision. Since 1989 we have
      been using the technique proposed by J.B. Tebbetts in 1987 and published in
      detail in the July, 1994 issue of "Plastic and Reconstructive Surgery". The
      authors feel that Force Vector Tip Rhinoplasty has been the only true innovation
      since Joseph (1931). Moreover, because of its content, this technique has
      exceeded the general term of open rhinoplasty. Indeed, this term is extremely
      general and simply indicates what surgical route is used. Nevertheless, the
      access route alone does not justify the choice of technique. On the other hand,
      what is truly innovative is the particular philosophy and technical aspects of
      Vector Rhinoplasty. In fact, by adding particular suture points and cartilaginous
      graft along calculated, extremely precise force lines, it is possible to modify
      the nasal skeleton. This is achieved with a steady, direct control and without
      damaging the delicate structures being supported. The term "Optimized Force
      Vector Tip Rhinoplasty" clearly depicts the concept, not only of a more complex
      access route; it also underlines the advantages in terms of intraoperative
      diagnostics, precision in performance and stability in time.

PMID- 9027202
TI  - ["Functional" neurovascular decompressive surgery of cranial rhino- base in
      headaches with rhinogenic triggering].
AB  - Today one must include neurovascular decompression of the rhino-cranial base
      among the various forms of functional nasal surgery and the classical chapter on
      "Cephalea of rhinological origin" must be reviewed. In fact, all those forms of
      "apparently primary" headaches (i.e. migraine with and without aura, cluster
      headache, chronic paroxysmal migraine, tension headache) which have a central
      peripheral etiopathogenesis due to a documented (CT) reduction in the volume of
      the "subcribriform ethmoid-sphenoidal chambers" affecting the hemoangiokinetics
      of endo-exocranial anastomotic circulation in this area. Rhino-cranial base
      neurovascular decompression surgery is described employing a "septo-ethmoid
      sphenectomy". This surgery can either be conservative or radical, reaching the
      third degree monolateral with selective trigeminal-vegetative deafferentiation;
      this makes it possible to save the sense of smell, resolve the controlateral pain
      by decompressing the blood flow and even eliminate controlateral stasis. In
      addition, in a high percentage of cases, symptoms of neurological deficit or
      central irritation (i.e. visual aura, senso-motory palsy, epilepsy) disappear or
      are markedly improved after surgical elimination of the "peripheral rhinogenetic
      trigger". In a sample of 1000 of the 2124 patients who had undergone surgery from
      1964 through the end of 1994, yearly follow-ups indicated that surgery cured or
      substantially improved 88%. On the other hand in 204 patients with similar forms
      of cephalea in advanced prophylaxis, 98% showed healing with "rapid disjunction
      of the palate" through "ortognatorhinodoncy" aimed at decompressing the
      neurovascular structure of the subcribrose chamber.

PMID- 9027203
TI  - [Experimental endolymphatic hydrops and distortion otoacoustic emission].
AB  - The present investigation was designed to measure distortion-product otoacoustic
      emissions (DPOAEs) in a group of guinea pigs with endolymphatic hydrops in order
      to obtain normative data in this particular field. The-DPOAE's results were
      compared with compound action potential (CAP) outcomes to analyze the value of
      DPOAE measurements in audiologic screening. Thirty albino guinea pigs were used.
      Recording sessions were performed before the hydrops and 10,17 and 24 days
      thereafter. DPOAE measurements showed specific patterns of alteration providing
      quantitative data of the severity of the impairment and the specific frequencies
      involved. The close relationship of the functional effects of hydrops on the
      results of CAPs and DPOAEs suggests the potential contribution of DP testing to
      monitor the progression of the cochlear dysfunction of the hydropic ear.

PMID- 9027204
TI  - [Selective vestibular neurectomy: a comparison of techniques].
AB  - The surgical treatment of patients suffering from incapacitating peripheral
      vertigo is still controversial. In the ENT Department of the Civil Hospital of
      Venice 43 patients with disabling menieric vertigo spells underwent a selective
      vestibular nerve section employing either a retrosigmoid (25 cases) or a
      retrolabyrinthine approach (18 cases) between 1991 and 1993. The two approaches
      are compared with regard to surgical technique, pre- and postoperative
      complications and i.e. functional results, i.e. vertigo control and hearing
      preservation. Functional results, classified according to the guidelines reported
      by the Committee on Hearing and Equilibrium of the AAO-HNS in 1985 did not show
      substantial differences. We obtained complete vertigo control in 95% of the
      patients and hearing was conserved at the preoperative level in almost all of the
      cases. The retrosigmoid approach demonstrated distinct advantages with regard to
      the surgical technique employed; it was faster, offered a wider surgical field in
      the cerebello-pontine angle and brought about fewer peri- and postoperative
      complications.

PMID- 9027205
TI  - [Laryngeal vertical partial surgery. Surgical techniques. Oncological and
      functional results].
AB  - We present the results of a retrospective study of 467 patients treated with
      conservative surgery for glottic carcinomas at the ENT department of the
      "Gregorio Maranon" Hospital between 1962-1993. The disease was staged using the
      criteria set forth in 1988 by the AJCC, and 27.7% patients were intermediate to
      advanced stages. Our theoretic treatment protocol is presented. The 5 years
      uncorrected actuarial survival related to stage was 85.6%, 71.4% and 71% for
      stages I, II and III respectively. In stages I and II local failure occurred in
      22.4% when patients were treated by laryngofisure and 10.8% when treated with
      hemilaryngectomy. The 5 years local control related to stage was 92.6%, 81.72%
      and 73.24% for stages I, II and III respectively. In stages I and II the 5 years
      survival with voice was 75.2% when the patients were treated with radiotherapy
      and 84.9% when treated with partial laryngectomy. Functional results have been
      evaluated according to a three grade scale. Good and fair results were 91.1% for
      the quality of voice, 99.7% for swallowing and 97.6% for respiration.

PMID- 9027207
TI  - [Round table. Cervico-facial oncological reconstructive surgery].

PMID- 9027206
TI  - [Differentiated carcinoma in autonomously functioning thyroid nodule: case
      report].
AB  - This paper report a case of autonomously functioning thyroid nodule, firstly
      occurred in a 13 years old women, complicated 9 years later by hyperthyroidism,
      with no response to thyreostatic treatment, hystologically diagnosed as papillary
      carcinoma, in a thyroid gland affected by Hashimoto's thyroiditis, with cervical
      bilateral lymph node metastasis. In literature the rate of coexisting
      hyperthyroidism, chronic thyroiditis and differentiated carcinoma is low; thus
      thyroid malignancies are very rare in young people. In this patient the large
      autonomously functioning nodule was entirely made of neoplastic tissue, while in
      the remaining thyroid there was no evidence of adenomatous tissue. Moreover,
      thyreostatic treatment failed in controlling hyperthyroidism. The Authors
      consider these facts as indirect evidences that this is a rare case of
      hyperfunctioning differentiated thyroid carcinoma.

PMID- 9027208
TI  - Bioluminescence and chemiluminescence literature. 263 references concerning
      nitric oxide and chemiluminescence, with some from the chemical literature but
      mainly from the life science literature (1964-early 1996).

PMID- 9027209
TI  - Bioluminescence and chemiluminescence literature. 113 references concerning green
      fluorescent protein (GF) (1975-1996).

PMID- 9027210
TI  - Triterpene and steroid saponins isolated from two Melilotus species.
AB  - Four new triterpene saponins of the oleanan series-melilotosides I, II, III, IV
      and nonglycosylated soyasapogenol B have been isolated from roots of Melilotus
      albus Medik. (Leguminosae) and four steroid saponins were isolated from M.
      tauricus (Bieb.) ser. seeds. The chemical structure of the saponins and of their
      aglycone was proved based on chemical transformations and spectral data.
      Melilotoside I has the structure of 3-O-[a-L-arabinopyranosyl] soyasapogenol B,
      melilotoside II that of 3-O-[beta-D-galactopyranosyl-(1-->2)-O-alpha-L
      arabinopyranosyl] soyasapogenol B, melilotoside III that of 3-O-[alpha-L
      rhamnopyranosyl-(1-->2)-O-beta-D-galactopyranosyl-(1-->2)-O -alpha-L
      arabinopyranosyl] soyasapogenol B, and melilotoside IV that of 3-O-[alpha-L
      rhamnopyranosyl-(1-->2)-[alpha-L-arabinopyranosyl-(1- ->3)]- O-beta-D
      galactopyranosyl-(1-->2)-O-alpha-L-arabinopyranosyl soyasapogenol B. The steroid
      saponins have been identified as 3-O-beta-D-glucopyranoside-diosgenin (V); 3-O
      alpha-L-rhamnopyranosyl (1-->2)-[alpha-L-rhamnopyranosyl(1-->3)-O-beta-D
      glucopyranoside- diosgenin (VI),26-O-beta-D-glucopyranoside (25R)-furost-5-ene
      3beta,22alpha, 26-triol (VII), and 3-O-alpha-L-rhamnopyranosyl(1-->4)-alpha-O
      beta-D- glucopyranoside(25R)-furost-5-ene 3beta,22alpha,26-triol-26-O-beta-D-
      glucopyranoside (VIII).

PMID- 9027211
TI  - Regulatory effects of saponins in the pathogenesis of root rots in cereal crops.

PMID- 9027212
TI  - [Transsexualism and legal proceedings].
AB  - One may not ignore the legal problem to which the transsexuals are exposed, once
      they have to search medical care. In Belgium, there does not exist any laws,
      which deal with the change of sex, although such laws would be very important for
      transsexual patients. On the other hand, change of the first name has been
      regulated by law. The actual knowledge of this problem is reviewed in this paper.

PMID- 9027214
TI  - Working solo, my first job.

PMID- 9027213
TI  - [Contribution of Abrams Griffiths' graphic charts in the analysis of urinary
      urgency in women].
AB  - The simplest way to obtain a meaningful result about detrusor pressure and
      urethral function is to have the plot superimposed on the Abrams-Griffiths
      nomogram. This concept is used to obtain information related to subvesical
      obstruction due to prostatic hypertrophy in male. We show herein that this type
      of analysis allows an objective estimate of pressure-flow relationships and
      permit simplification in analyzing micturition in women.

PMID- 9027215
TI  - Spinal morphine in remote practice.

PMID- 9027216
TI  - Enoxaparin (Clexane) HITS.

PMID- 9027217
TI  - Interpretation of oligonucleotide mass spectra for determination of sequence
      using electrospray ionization and tandem mass spectrometry.
AB  - Procedures are described for interpretation of mass spectra from collision
      induced dissociation of polycharged oligonucleotides produced by electrospray
      ionization. The method is intended for rapid sequencing of oligonucleotides of
      completely unknown structure at approximately the 15-mer level and below, from
      DNA or RNA. Identification of sequence-relevant ions that are produced from
      extensive fragmentation in the quadrupole collision cell are based primarily on
      (1) recognition of 3'- and 5'- terminal residues as initial steps in mass ladder
      propagation, (2) alignment of overlapping nucleotide chains that have been
      constructed independently from each terminus, and (3) use of experimentally
      measured molecular mass in rejection of incorrect sequence candidates. Algorithms
      for sequence derivation are embodied in a computer program that requires < 2s for
      execution. The interpretation procedures are demonstrated for sequence location
      of simple forms of modification in the base and sugar. The potential for direct
      sequencing of components of mixtures is shown using an unresolved fraction of
      unknown oligonucleotides from ribosomal RNA.

PMID- 9027218
TI  - Development of a surface acoustic wave immunosensor.
AB  - In this paper the first application of horizontal polarized surface acoustic
      waves (HP-SAW) in LiTaO3 for an immunosensor is presented. A SAW device with two
      paths, a sensitive path and a reference path operating in liquid at 345 MHz, is
      used as the sensor. Antigens and antibodies were both immunoglobulins. The
      antibodies were immobilized via protein A on the sensitive path with a mass
      density of 0.4 ng/mm2, as shown by ELISA measurements. A theoretical detection
      limit of approximately 33 pg and a high sensitivity of 110 kHz/(ng/mm2) could be
      derived from the experiments. High signal enhancement factors of 4.5 and 12 are
      achievable by gold colloid labeled antigens with colloid diameters of 5 and 10
      nm, respectively. Specificity of the antibody was demonstrated by a preabsorption
      experiment. As a further antibody/antigen system the binding of the anti-human
      serum albumin (HSA) to HSA was examined.

PMID- 9027219
TI  - Mixed potential response mechanism of cobalt electrodes toward inorganic
      phosphate.
AB  - The potentiometric response mechanism of a previously reported phosphate ion
      sensitive electrode based on a surface-oxidized cobalt metal is examined. Beyond
      response to phosphate, the cobalt electrode is found to respond to changes in the
      partial pressure of oxygen in the sample solution. the potentiometric response
      toward phosphate ions and molecular oxygen is shown to depend on the sample
      stirring rate as well as the pH, ionic strength, and nature of the buffer salts
      present within the test solution. X-ray photoelectron spectroscopy studies of the
      cobalt electrodes, in conjunction with cyclic voltammetric measurements, suggest
      that the potentiometric response originates from a mixed potential resulting from
      the slow oxidation of cobalt and simultaneous reduction of both oxygen and Co2+
      at the surface of the electrode. In contrast to an originally proposed host-guest
      mechanism, the present mixed potential mechanism more accurately explains
      behavior of oxidized cobalt electrodes in the presence of phosphate and oxygen
      species.

PMID- 9027220
TI  - Use of moment of inertia in comparative molecular field analysis to model
      chromatographic retention of nonpolar solutes.
AB  - A quantitative structure-retention relationship (QSRR) was developed from
      chromatographic data on 31 unsubstituted 3-6 ring polycyclic aromatic
      hydrocarbons (PAHs) using the 3D-QSAR method known as comparative molecular field
      analysis (CoMFA). The resulting CoMFA model gave an excellent correlation to high
      performance liquid chromatography retention data for these PAHs yielding r2
      values of 0.947 (conventional) and 0.865 (cross-validated). The steric and
      electrostatic contributions to the CoMFA model were 100% and 0%, respectively. A
      unique feature of this study was the use of moment of inertia, I, as a basis for
      CoMFA alignment of the PAH molecules. The moment of inertia also provided an
      alternative method for calculating the solute length-to-breadth ratio (L/B),
      which has been applied in previous QSRR studies as a molecular descriptor for PAH
      retention. By virtue of its mathematical simplicity and lack of ambiguity, the
      present derivation of L/B from I offers several advantages over other geometry
      based schemes. Finally, Ix was evaluated for use as a molecular descriptor in
      QSRR regression analysis to predict the log of the retention index (log I) for
      these PAHs. The correlation with PAH retention was weak when the moment of
      inertia was considered alone but improved dramatically (r2 = 0.928) when the
      moment of inertia and connectivity index chi were used in combination as
      descriptors.

PMID- 9027221
TI  - Micellar electrokinetic chromatography separations and analyses of biological
      samples on a cyclic planar microstructure.
AB  - Micellar electrokinetic capillary chromatography (MECC) separations and analyses
      of biological samples on a planar glass microchip capillary electrophoresis
      device with laser-induced fluorescence solute detection are discussed. A cyclic
      channel system which permits dead volume free repeated column switching and thus
      the use of various channel lengths together with a relatively low applied
      separation voltage is described. It features an unbiased, dead volume free
      electrokinetic sample inlet system of approximately 12 pL. Because of the small
      cross section and favorable heat dissipation in glass microstructures, MECC
      separations with an electric field strength of up to 2000 V/cm achieving
      efficiencies of submicrometer plate heights can be performed. After a separation
      length of 2 cm, six fluorescein isothiocyanate labeled amino acids are shown to
      be separable within a few seconds and with an imprecision for peak areas (or
      heights) and detection times of < 2% and < 0.5%, respectively. Without
      application of electrokinetic solute stacking, the detection limit of fluorescein
      isothiocyanate labeled arginine is 3.3 nM, corresponding to approximately 40 zmol
      injected. Furthermore, the feasibility of directly applying human urine and serum
      samples onto the uncoated channel system is demonstrated and first data of the
      successful performance of a chip-based MECC immunoassay for serum theophylline
      are presented. Compared to MECC in conventional fused-silica capillaries, MECC
      analyses on microchips can be performed 1-2 orders of magnitude faster, with
      higher efficiency and at no expense of accuracy and precision. Furthermore,
      versatility is shown to be much increased with the use of a cyclic rather than a
      single-path channel system. The MECC separation efficiency of fluorescein
      isothiocyanate labeled amino acids is shown to be comparable to that obtained by
      gel electrophoresis performed in the same chip layout.

PMID- 9027222
TI  - Comparison of the sensitivities of various derivatives of oligosaccharides in
      LC/MS with fast atom bombardment and electrospray ionization interfaces.
AB  - Sensitivities of the following derivatives of oligosaccharides in MS and LC/MS
      with frit FAB and ESI interfaces were compared under the conditions where samples
      were supplied to the probes in solutions at constant rates: 2-aminopyridine, 4
      aminobenzoic acid ethyl ester (ABEE), 1-phenyl-3-methyl-5-pyrazolone (PMP) as
      well as 4-methoxyphenyl analogue, 2-aminoethanethiol, and 2-aminobenzenethiol. In
      FAB-MS, maltopentaose labeled with ABEE gave the most abundant [M + H]+ ions in
      positive ion mode when ionized in thioglycerol or glycerol matrix supplied in 50%
      (v/v) aqueous methanol. The lowest limit of detection was obtained for this
      compound in these matrices in water. The [M - H]- ion in negative ion mode was
      also abundant in all matrices examined in both 50% (v/v) aqueous methanol and
      water. On the other hand PMP derivatives gave the highest sensitivities in ESI-MS
      under the optimized conditions. On the basis of these findings, authentic
      oligosaccharides and oligosaccharides derived from a few glycoprotein samples
      were analyzed by LC/MS with frit FAB and ESI interfaces. The results indicated
      the usefulness of these derivatives for simultaneous microanalysis of
      oligosaccharides.

PMID- 9027223
TI  - Overoxidized polypyrrole-coated carbon fiber microelectrodes for dopamine
      measurements with fast-scan cyclic voltammetry.
AB  - Thin films of overoxidized polypyrrole have been electro-chemically coated onto
      carbon fiber microelectrodes and used for dopamine measurements with background
      substracted, fast-scan cyclic voltammetry at a scan rate of 300 V/s. The films
      were stable on the electrode surface only when the electrodes were scanned to
      high potentials (1400 mV vs SSCE) in pH 7.4 aqueous buffer. Dopamine sensitivity
      and ascorbate and dihydroxyphenylacetic acid (DOPAC) rejection at the
      overoxidized polypyrrole-coated electrode were compared to those at carbon fiber
      electrodes coated with Nafion, a perfluorinated ion-exchange material. At 300
      V/s, the overoxidized polypyrrole-coated electrode was almost 3 times more
      sensitive to dopamine than an uncoated disk electrode. Furthermore, the films
      were as effective as Nafion in the attenuation of the response to ascorbate and
      DOPAC, common interferences of dopamine in vivo. Overoxidized polypyrrole-coated
      electrodes maintained a stable response to dopamine for several hours when
      implanted in the rat brain. The electrochemical deposition procedure was
      effective at both elliptical and cylindrical electrodes. This is in contrast to
      the dip-coating procedures employed with Nafion films that lead to nonuniform
      coatings at cylindrical electrodes.

PMID- 9027224
TI  - High-resolution MALDI Fourier transform mass spectrometry of oligonucleotides.
AB  - The matrix-assisted laser desorption/ionization (MALDI) method has been used with
      an external ion source Fourier transform mass spectrometer (FIMS) to analyze
      single-stranded, mixed-base oligomers of DNA. It is demonstrated that ultrahigh
      mass resolution (830 000 fwhm) can be achieved for small oligomers, and high
      resolution (136 000 fwhm) can be achieved for a 25-mer at m/z 7634. MALDI-FTMS
      can clearly separate the molecular ion peaks from analyte-matrix adduct peaks and
      alkali metal-containing species that result from replacement of hydrogen ions
      with sodium or potassium ions at multiple sites along the phosphate backbone.
      Previous MALDI-FTMS studies of oligonucleotides had two limitations: (1) low
      sensitivity due to difficulty in trapping the high kinetic energy ions made by
      the laser and (2) fragmentation of the ions due to the long delay (tens to
      hundreds of milliseconds) between their formation and detection. Both of these
      problems are alleviated in the present study. With the external ion source FTMS
      instrument, ions made by MALDI are injected at low energy into the analyzer cell
      by a rf-only quadrupole ion guide, captured by gating the voltage on the trapping
      plates, and cooled by a 0.5-s pulse of argon gas. Under these conditions,
      fragmentation is minimized, and DNA ions can be trapped in the FTMS analyzer cell
      for greater than 50 s. Sensitivity is also improved, as demonstrated by detection
      of 1 pmol of a single-stranded, mixed-base 20-mer of DNA, with a signal-to-noise
      ratio greater than 20:1.

PMID- 9027225
TI  - Matrix-assisted laser desorption ion trap mass spectrometry: efficient trapping
      and ejection of ions.
AB  - The present paper explores the coupling of a matrix-assisted laser
      desorption/ionization (MALDI) ion source with an ion trap mass analyzer, with
      particular emphasis on the development of methods for improving the efficiency of
      ion trapping and ejection. A technique is described for directly measuring, for
      the first time, the trapping efficiency of peptide ions produced in a remote
      external MALDI ion source. The technique was used to devise an improved scheme
      for trapping, which yielded efficiencies as high as 39%. An improved
      understanding of the resonant ejection process led us to a new resonant ejection
      parameter set that increased the ejection efficiency by 1 order of magnitude over
      more conventionally used parameter sets and allowed for marked improvements in
      the mass resolution of ions with m/z > 2500. The presently described improvements
      in the efficiencies of ion trapping and ejection together with improved methods
      for isolating and fragmenting ions (Qin, J.; Chait, B.T.Anal. Chem., following
      article in this tissue) lay the foundation for highly sensitive MALDI ion trap
      mass spectrometry of proteins (Qin, J.; et al. Anal. Chem. 1996, 68, 1784-1791).

PMID- 9027226
TI  - Matrix-assisted laser desorption ion trap mass spectrometry: efficient isolation
      and effective fragmentation of peptide ions.
AB  - Effective analysis of the sequence of peptides using matrix-assisted laser
      desorption/ionization (MALDI) tandem ion trap mass spectrometry requires
      efficient mass isolation and the ability to induce extensive sequence-specific
      fragmentation. The present paper describes a new excitation scheme, which we term
      red-shifted off-resonance large-amplitude excitation (RSORLAE), that can deposit
      higher amounts of internal energy in ions than is feasible with conventional
      resonant excitation. The new method provides an effective means for inducing
      fragmentation of MALDI-produced peptide ions with m/z values up to 3500. Prior to
      excitation, it is necessary to isolate ions of interest with high efficiency. We
      demonstrate that isolation efficiencies of > 95% can be achieved by careful
      design of the rf scan functions used during ion isolation. In particular, sudden
      transitions in the amplitude of the rf field (from low to high amplitudes) must
      be avoided. The combined improvements in the efficiency for ion isolation and the
      efficacy of ion activation make MALDI tandem ion trap mass spectrometry a
      practical tool for the characterization of proteins with high sensitivity.

PMID- 9027227
TI  - Coupling of MALDI-TOF mass analysis to the separation of biotinylated peptides by
      magnetic streptavidin beads.
AB  - Extraction of biotinylated peptides by streptavidin magnetic beads has been
      directly coupled to the MALDI-TOF mass analysis. The elution of peptides from the
      beads is achieved by first mixing the beads with the MALDI matrix solution and
      removing, after a few minutes, the beads with a magnet; then, the matrix solution
      containing the biotinylated peptide is directly mass analyzed by MALDI. Three
      examples are presented to show the capabilities of this procedure to detect
      biotinylated peptides present at very low concentrations in complex mixtures.
      Detection limits of less than 100 finol can be achieved. Such a coupling strategy
      is of great interest to investigate peptide/ protein interactions.

PMID- 9027228
TI  - Multicomponent NMR titration for simultaneous measurement of relative pKaS.
AB  - An NMR titration method has been developed to simultaneously measure the
      difference in acid dissociation constants (delta pKa) of two or more compounds
      with high precision and accuracy. The delta pKa between the conjugate acids of
      the two stereoisomers of 4-tert-butylcyclohexylamine 1 was determined in a single
      1H NMR titration experiment. A mixture of the two stereoisomers was titrated with
      DCI in a 3:1 (v/v) mixture of CD3OD/D2O. From the variations of the H1 chemical
      shifts the ratio of the acidity constants was determined. The trans stereoisomer
      1t was found to be the more basic by 0.121 +/- 0.002 pK unit. A repeat titration
      in DMSO-d6 also found 1t to be the more basic, by 0.217 +/- 0.003 pK unit. The
      delta pKa between the two stereoisomers of 4-tert-butylcyclohexanecarboxylic acid
      2 was determined in both of these solvents using 1H and 13C NMR. Thermodynamic
      parameters delta delta H degree and delta delta S degree were evaluated from the
      temperature dependence of delta pKa. To further demonstrate the utility of this
      method, the delta pKas of the conjugate acids of the four stereoisomers of 2
      decalylamine 3 were determined in a single 1H NMR titration experiment. The
      cis,cis stereoisomer (3cc) was found to be the most basic, with the cis,trans
      (3ct), trans,cis (3tc), and trans,trans (3tt) less basic by 0.012 +/- 0.003,
      0.037 +/- 0.004, and 0.141 +/- 0.005 pK unit, respectively. A second four
      component titration was also performed with the two 4-tert-butylcyclohexylamines
      (1) and the two trans-2-decalylamines (3tc, 3tt).

PMID- 9027229
TI  - Oligonucleotide sequence and composition determined by matrix-assisted laser
      desorption/ionization.
AB  - Molecular weight measurements of several oligonucleotides ranging in size from 12
      to 60 bases were performed by matrix-assisted laser desorption/ionization with a
      time-of-flight mass spectrometer (MALDI-TOF). In each case, the mass accuracy was
      better than 0.1%. Sequences for two 12-base oligonucleotides and a 24-base
      oligonucleotide were determined using calf spleen phosphodiesterase to
      sequentially cleave from the 5' end. A MALDI-TOF spectrum of the digest mixture
      shortly after the addition of the enzyme produced a characteristic
      oligonucleotide ladder. Molecular ions in the mass spectrum corresponded to the
      products of enzymatic cleavage, and the mass differences between these peaks
      identified the individual nucleotides. The resolution and mass accuracy of MALDI
      TOF were sufficient to unambiguously identify the individual nucleotides in the
      12- and 24-base strands.

PMID- 9027230
TI  - Chiral separation of chloroquine using heparin as a chiral selector in high
      performance liquid chromatography.
AB  - The chiral selectivity of a commercially available heparin affinity column was
      investigated for chloroquine. The (+) enantiomer eluted first, which is
      consistent with results reported previously using heparin as a chiral additive in
      capillary zone electrophoresis. The effects of pH, ionic strength, and organic
      modifier on the enantiodiscrimination were explored. A combination of
      electrostatic and hydrophobic interactions seems to play an important role in the
      enantiodiscrimination exhibited by this novel phase.

PMID- 9027231
TI  - Determination of nucleic acids by a resonance light-scattering technique with
      alpha, beta, gamma, delta-tetrakis[4-(trimethylammoniumyl)phenyl]porphine.
AB  - The resonance light-scattering technique, using a spectrofluorometer, was first
      developed as a sensitive instrumental analysis method. At pH 7.48 and ionic
      strength 0.004, the extent of light-scattering of alpha, beta, gamma, delta
      tetrakis[4-(trimethylammoniumyl)phenyl]porphine (TAPP) is enhanced by nucleic
      acids near 432 nm. There are linear relationships between the enhanced extents of
      light-scattering and the concentrations of nucleic acids in the range of 1.8 x
      10(-7)-10.8 x 10(-7) M for calf thymus and fish sperm DNA and in the range of 1.8
      x 10(-7)-1.8 x 10(-6) M for yeast RNA. The limit of determination (3 sigma) is
      4.1 x 10(-8) M for calf thymus DNA, 4.6 x 10(-8) M for fish sperm DNA, and 6.7 x
      10(-8) M for yeast RNA. Mechanism study indicates that nucleic acids react with
      the title porphyrin in two modes, depending on the concentrations of nucleic
      acids. When the molar ratio of nucleic acids to TAPP is smaller than 4:1, the
      hypochromicity and fluorescence quenching of TAPP by nucleic acids appear, and
      the enhancement of resonance light-scattering can be observed. When the molar
      ratio of nucleic acids to TAPP is larger than 4:1, a new fluorescent complex is
      formed.

PMID- 9027232
TI  - Characterization of an erbium-doped fiber amplifier as a light source and
      development of a near-infrared spectrophotometer based on the EDFA and an
      acoustooptic tunable filter.
AB  - A novel light source for the near-infrared region which has the highest intensity
      and widest spectral bandwidth of all near-IR light sources has been developed.
      The system is based on a single-mode fiber (about 18 m long) doped with Er3+ ion.
      The doped ion produces amplified spontaneous emission (ASE) in the near-IR region
      (from 1500 to 1600 nm) when it is excited by a diode laser at 980 nm. Because the
      diode laser is fusion-spliced directly to the doped fiber, the system is compact,
      all-solid-state, reliable, and stable and requires little maintenance. Its ASE
      output intensity was found to be comparable with those of diode lasers currently
      available for this near-IR region and is much higher than those of conventional
      halogen-tungsten lamps and the so-called (high-intensity) superluminescent light
      emitting diodes (SLEDs). Its spectral bandwidth is, however, much wider than
      those of the diode lasers and the SLEDs. Even higher intensity can be obtained
      from the doped fiber when a low-intensity (1 mW) light from a 1550-nm laser diode
      is introduced into the doped fiber. The intensity is enhanced (up to 7 times
      compared to the ASE) because the input light is amplified by the doped fiber.
      Furthermore, the output intensity of this erbium-doped fiber amplifier (EDFA) can
      be appropriately adjusted to provide relatively higher output intensity at any
      range of wavelengths (within this 1500-1600-nm region) by simply changing the
      temperature and/or the driven current of the input diode laser. Subsequently, an
      acoustooptic tunable filter was used to provide a means to spectrally tune the
      EDFA rapidly and to develop an all-solid-state, compact near-IR spectrophotometer
      which not only is very sensitive, stable, and reliable but also has a very high
      throughput. This spectrophotometer can detect water in ethanol at a limit of
      detection of 10 ppm. More importantly, the high through-put makes it possible to
      use the instrument to measure spectra of highly absorbing samples (e.g.,
      absorption spectrum of 1.0 M Pr3+ aqueous solution through four sheets of paper);
      measurements which are currently not possible with halogen-tungsten lamp-based
      spectrophotometers.

PMID- 9027233
TI  - Correction of ion source nonlinearities over a wide signal range in continuous
      flow isotope ratio mass spectrometry of water-derived hydrogen.
AB  - Ion source nonlinearities are characterized over a wide range of signal
      intensities characteristic of complex mixtures, and correction schemes are
      proposed and evaluated for high-precision determinations of D/H ratios from water
      via an on-line reduction system facilitating continuous-flow isotope ratio mass
      spectrometry. Hydrogen isotope ratios are shown to be sensitive to analyte
      pressure in the IRMS ion source with or without carrier gas admitted with
      analyte, indicating that analyte level must be taken into account for isotope
      ratio calculation. Two experimentally simple "peakwise" correction schemes, in
      which hydrogen isotope ratios are corrected after peak identification and ratio
      calculation, are compared to the method routinely applied to static dual-inlet
      IRMS measurements. It is demonstrated that traditional linear correction applied
      to continuous-flow peaks is adequate over small signal ranges, about m/z 2 +/-
      0.5 V; however, a second order correction is required for acceptable accuracy and
      precision over larger ranges. In addition, tests of the peakwise algorithms were
      made using a set of liquid water samples with delta D Tap Water over the range of
      39-407/1000 with uncorrected data with precisions of SD-(delta D Tap Water <
      34/1000 and accuracy within 11/1000. Peakwise correction using a linear
      calibration model resulted in substantial improvements in precision (SD <
      10/1000) and accuracy (< 4/1000). Peakwise-corrected data, calibrated using a
      second-order regression to account for unmatched detector response, are still
      further improved to accuracy within 2/1000 from the calibration curve. The
      peakwise correction schemes are advantageous because of experimental simplicity
      when applied to peaks of the same or similar shapes. This study shows that ion
      source non-linearities in hydrogen analysis require correction for optimal
      analytical performance and can successfully be handled using straightforward
      procedures over the wide signal range required for chromatographic analysis.

PMID- 9027234
TI  - Evaluation of mass spectrometric methods applicable to the direct analysis of non
      peptide bead-bound combinatorial libraries.
AB  - Electrospray, matrix-assisted laser desorption, and time-of-flight secondary ion
      mass spectrometry have been explored as possible methods for the identification
      of active members of molecular combinatorial libraries. All three methods are
      found to yield accurate molecular weight information about a target molecule
      angiotensin II antagonist synthesized on a 40-microns polystyrene bead.
      Structural identification is also possible by accurate mass measurements to
      eliminate candidate structures with the same nominal mass and by analysis of the
      fragmentation patterns. In addition, the secondary ion mass spectrometry
      measurements yield spatially resolved spectra from a single bead after exposure
      to a suitable gas which clips the covalent bond at the linking position. All
      three approaches appear to offer a viable screening strategy of non-peptide
      libraries without the use of additional molecular tags.

PMID- 9027235
TI  - Product ion charge state determination via ion/ion proton transfer reactions.
AB  - Proton transfer from protonated pyridine to product anions derived from
      quadrupole ion trap collisional activation of the triply charged anion of the
      oligonucleotide 5'-d(AAAA)-3' and the 6- charge state of oxidized bovine insulin
      A-chain is shown to be a rapid and effective way to determine product charge
      states. The reactions are carried out in a quadrupole ion trap as part of a
      procedure involving three stages of mass analysis. It is demonstrated that the
      reactions can be driven at rates sufficiently high to convert 30-80% of the
      initial product anion population to second generation products in 50-200 ms. The
      use of ion/ion reactions enjoys significant advantages over the use of
      ion/molecule proton transfer chemistry. For example, ion/ion reactions are more
      universal than ion/molecule reactions due to their greater exothermicity, and
      ion/ion reactions allow for precise control over the timing of introduction and
      ejection of each reactant. Despite the high exothermicity of the reactions, no
      significant fragmentation of product ions derived from high-mass multiply charged
      anions is observed.

PMID- 9027236
TI  - Carboxylate and amine terminus directed fragmentations in gaseous dipeptide
      complexes with copper (II) and diimine ligands formed by electrospray.
AB  - Singly and doubly charged peptide complexes with copper(II) and 2,2'-bipyridyl
      (bpy) are formed in the gas phase by electrospraying water-methanol solutions
      containing the components. Collisionally activated dissociations at low kinetic
      energies of singly charged complexes of the [CuII(peptide-H)(bpy)].+ type provide
      information about the amino acid sequence for L-Phe-Leu, L-Leu-Phe, L-Phe-Pro, L
      Pro-Phe, L-Phe-Met, L-Met-Phe, L-Ser-Phe, L-Asp-Phe, and L-His-Phe. Dissociations
      of doubly charged complexes of the [CuII(peptide)(bpy).2+ type also allow
      identification of the N- and C-terminal amino acid residues. Leucine and
      isoleucine residues are readily distinguished in L-Ala-Leu and L-Ala-Ile through
      dissociations of their Cu complexes. Ion dissociation mechanisms, as elucidated
      by deuterium labeling, are discussed.

PMID- 9027237
TI  - Correction of mass spectral drift using artificial neural networks.
AB  - For pyrolysis mass spectrometry (PyMS) to be used for the routine identification
      of microorganisms, for quantifying determinands in biological and
      biotechnological systems, and in the production of useful mass spectral
      libraries, it is paramount that newly acquired spectra be compared to those
      previously collected. Neural network and other multivariate calibration models
      have been used to relate mass spectra to the biological features of interest. As
      commonly observed, however, mass spectral fingerprints showed a lack of long-term
      reproducibility, due to instrumental drift in the mass spectrometer; when
      identical materials were analyzed by PyMS at dates from 4 to 20 months apart,
      neural network models produced at earlier times could not be used to give
      accurate estimates of determinand concentrations or bacterial identities. Neural
      networks, however, can be used to correct for pyrolysis mass spectrometer
      instrumental drift itself, so that neural network or other multivariate
      calibration models created using previously collected data can be used to give
      accurate estimates of determinand concentration or the nature of bacteria (or,
      indeed, other materials) from newly acquired pyrolysis mass spectra. This
      approach is not limited solely to pyrolysis mass spectrometry but is generally
      applicable to any analytical tool which is prone to instrumental drift, such as
      IR, ESR, NMR and other spectroscopies, and gas and liquid chromatography, as well
      as other types of mass spectrometry.

PMID- 9027238
TI  - Mechanism of peptide separations by solid phase extraction capillary
      electrophoresis at low pH.
AB  - A device for on-line extraction and concentration of peptides from a dilute
      sample matrix prior to direct capillary electrophoretic analysis is described.
      The technique, termed solid phase extraction capillary electrophoresis (SPE-CE),
      can facilitate analysis of peptides in the low nanograms per milliliter range.
      Peptides from a sample matrix are adsorbed on a reversed phase resin (C-8 or C
      18) cartridge in-line with an uncoated fused-silica capillary and subsequently
      released for free zone electrophoresis by injection of an organic elutant. Unlike
      previous designs and commercially available packed-inlet capillaries, the device
      is easily constructed from common laboratory materials and is applicable to a
      wide range of conventional instrumentation and methods. This device and method
      has been developed for use in our laboratory as a stand-alone preparative
      technique, specifically to provide a second-dimensional orthogonal separation of
      biologically derived HPLC fractions of peptides in a single analysis. To this
      end, extensive effort was required in both device construction and method
      development to attain the successful separations which are reported in this
      study. Extractions of dilute peptide mixtures from sample injections exceeding,
      but not limited to, 20 times (48 microL) the capillary volume with apparent
      recovery greater than 80% are shown. The selectivity of extraction of individual
      components of a very dilute peptide mixture (31 ng/mL with 280 microL of sample
      injected) is presented. The ability to efficiently extract the individual
      peptides from the sample was found to be concentration-dependent for the
      individual peptide components over a 1600-field dilution of a common calibration
      mixture of nine model peptides. Varying the injected volume of elution buffer
      demonstrated the importance of minimizing the amount of buffer used to desorb
      peptides to maximize the resolution of individual peptides. This study highlights
      implementation for direct SPE-CE for peptide analysis and discusses for SPE tip
      induced mechanism through which reversal in electoosmotic flow occurs.

PMID- 9027239
TI  - Molded monolithic rod of macroporous poly(styrene-co-divinylbenzene) as a
      separation medium for HPLC of synthetic polymers: on-column precipitation-
      redissolution chromatography as an alternative to size exclusion chromatography
      of styrene oligomers and polymers.
AB  - A process for the separation of styrene oligomers and polymers by size and
      composition using a novel separation medium has been demonstrated. The process
      involves precipitation of the macromolecules on the molded macroporous rod
      columns, followed by progressive elution utilizing a simple gradient of the
      mobile phase. Molded macroporous rod columns are ideally suited for this
      technique because convection through the large pores of the rod enhances the mass
      transport of large analyte molecules and accelerates the separation process.
      Styrene oligomers and polymers are separated in a 50-mm x 8-mm-i.d. column using
      a solvent gradient composed of a poor solvent such as water, methanol, or
      acetonitrile and increasing amounts of a good solvent, tetrahydrofuran. Excellent
      separations are obtained, demonstrating that precipitation-redissolution can be a
      suitable alternate to size exclusion chromatography (SEC) of some polymers.
      Compared to SEC, the gradient elution separation can be achieved at higher flow
      rates in a much shorter time. Precipitation-redissolution with gradient elution
      can also be used for the separation of copolymers, for which the process is
      controlled not only by molecular weight but also by the composition of the
      copolymers.

PMID- 9027241
TI  - [The transverse movement of the temporo-mandibular joint (translation movement)
      of the dog, also with reference to dysplasia of this joint in the dachshund].
AB  - Contrary to the accepted opinion, transverse movement is possible in the temporo
      mandibular joint of the dog. This movement is arched and is important for
      mastication. Analysis of transverse movement of the temporo-mandibular joint was
      done in 20 dog breeds. Accidentally dysplasia of the temporo-mandibular joint was
      found in the dachshund, a phenomenon which has not been described before.

PMID- 9027240
TI  - Analysis of gamma-(cholesteryloxy)butyric acid in biologic samples by
      derivatization with 5-(bromomethyl)fluorescein followed by high-performance
      liquid chromatography with laser-induced fluorescence detection.
AB  - This report describes the first application of 5-(bromo-methyl)fluorescein (5
      BMF) for the quantitation of a pharmaceutically relevant carboxyl-containing
      analyte in a biological matrix. An analytical method for quantitation of gamma
      (cholesteryloxy)butyric acid (CBA), a relatively new antitumor agent, in
      different tissues of Sprague-Dawley rats was developed. 5-BMF was employed to
      form a stable and spectrally well-characterized conjugate of CBA. The
      derivatization yield was maximized by optimizing several reaction variables. The
      conjugate was separated by high-performance liquid chromatography and quantitated
      by a laboratory-constructed argon ion laser fluorometer. The detection limits for
      CBA were 4.6 x 10(-9) and 6.34 x 10(-11) M by conventional and laser-induced
      fluorescence (LIF), respectively. A derivatization limit of detection of 1.85 x
      10(-9) M was achieved by LIF for the conjugate The analytical method was useful
      for quantitation of CBA in various tissues in the picogram per milliliter range.

PMID- 9027242
TI  - [On the costal articulations XI, XII, XIII of the domestic cat (Felis catus)].
AB  - The costal articulations XI, XII, XIII of the cat are simple, synovial joints.
      This dot-shaped suspension of the last ribs from the spinal column and the
      existence of a costo-vertebral ligament are coordinated functionally.

PMID- 9027243
TI  - [Microangioarchitecture of the mucosa of the antrum pyloricum in rabbit].
AB  - Microangioarchitecture of the mucosa of the Antrum pyloricum in rabbit was
      studied by optical and scanning electron microscopy. Passing the lamina
      muscularis mucosae, arteries of the submucosa reach the lamina propria and branch
      in to the terminal arteries forming a subglandular network. From these vessels,
      two capillary nets arise. The first forms a capillary skein around the base of
      the glands, while the second ascends along the tubuli, moving upwards to the
      surface along the glandular tubuli. These ascending capillaries also arise
      directly from the subglandular arterioles of the lamina propria, as well as from
      capillaries of the basal parts of the glandular tubuli. Subepithelial capillaries
      form arcuate loops with 2-3 venules or collecting venules, which run into the
      venous net in the basal region of the lamina propria. Numerous horizontal
      interconnections exist between the collecting venules but arteriovenous
      anastomosis in the mucosa was not observed.

PMID- 9027244
TI  - [The differentiation of the surface mucous-cell line in the abomasum of the adult
      cow].
AB  - The differentiation of the surface mucous-cell lineage during physiological cell
      renewal was investigated using light and electron microscopy in the abomasal
      mucosa of adult cattle. The surface mucous cells constitute a morphologically and
      functionally heterogeneous population, whose members correspond to different
      developmental stages, OFFanged in a distoproximal gradient from the depth of the
      pit towards the free luminal surface. The cell lineage comprises immature pre-pit
      cells near the proliferative isthmus, mature pit cells within the foveola, and
      older interfoveolar cells lining the free surface. Ultrastructurally,
      differentiation can be traced towards a predominantly mucus-producing cell type
      and finally towards a surface-protective cell variant, which degenerates in situ
      and is extruded into the lumen without affecting epithelial integrity.

PMID- 9027245
TI  - [The analysis of systemic hemodynamics and of myocardial functional status in
      patients in critical states].
AB  - Timely diagnosis of disorders of the pumping function of the heart and its
      inotropic state, strained compensation, and failure of the compensatory potential
      are important for selecting the treatment strategy and predicting the disease
      course in critical patients. This paper presents the results of many-year
      investigations in this field. The contribution of right-ventricular insufficiency
      to the development of circulatory disorders is validated, as is the effect of
      artificial ventilation of the lungs on the function of the myocardium.
      Relationship between the severity of hemodynamic disorders and pathological
      process is described. The author validates the use of test exposures and
      functional tests in intensive care departments in order to assess the functional
      insufficiency and reduction of the reserve potential of the right and left heart.
      The potentialities of spectral analysis of the electrocardiographic signal in the
      early diagnosis of myocardial dysfunction and prediction of the disease course is
      shown.

PMID- 9027246
TI  - [Thrombocytic hemostasis in patients with severe craniocerebral trauma].
AB  - Platelet vascular hemostasis was assessed in 32 patients with slight
      craniocerebral injuries (SCCI) (Glasgow coma score 14-15) (group 1) on days 1, 3,
      5, and 7 and in 84 patients (score 3-8) (group 2) in the same terms and on days
      9, 14, and 21 after the injury. Under study were platelet count, spontaneous
      platelet aggregation and that induced by ADP, adrenalin, and ristomicin. Moderate
      disorders of platelet vascular hemostasis were revealed in all the patients; they
      were most of all expressed on day 5 and were mainly due to moderate disorders of
      the athrombogenicity of the vascular endothelium. The injury caused a manifest
      dysfunction of platelets connected with the developing disseminated intravascular
      blood coagulation and, specifically, with injury to the vascular endothelium.
      Spontaneous aggregation of platelets was the maximum on day 5 and coincided in
      time with an increase in Willebrand factor-dependent ristomicin-induced platelet
      aggregation (Willebrand factor is a marker of injury to the vascular
      endothelium). An increase of ristomicin-induced platelet aggregation was more
      often observed in the patients who died than in the survivors, and in those
      developing the respiratory distress syndrome (stages II-IV) and that combined
      with pneumonia.

PMID- 9027247
TI  - [Hyperbaric oxygenation as a method of intensive therapy].

PMID- 9027248
TI  - [Extrapulmonary fluorocarbon oxygenation].

PMID- 9027249
TI  - [The immunobiochemical mechanisms of the intoxication syndrome in acute diffuse
      peritonitis].
AB  - The course of diffuse peritonitis was studied in 211 patients with the reactive
      (25 patients), toxic (114), and terminal (65) stages. Besides routine treatment,
      local abdominal hypothermia, UV exposure of autoblood, and, if indicated,
      hyperbaric oxygenation and hemoperfusion were used in multiple-modality treatment
      of these patients. In addition to the common clinical tests, immunobiochemical
      monitoring of the function of medium-molecular peptides and index of their
      distribution, as well as of the fractions of circulating immune complexes and of
      IgA, IgM, and IgG was used to assess the severity of intoxication and treatment
      efficacy and predict the disease course and outcome. Intoxication of the organism
      was shown to lead to the formation of immunity shifts, involving, among other
      things, the humoral immunity.

PMID- 9027250
TI  - [The surgical operation as a component in the resuscitation assistance in severe
      combined chest trauma].
AB  - Assessment of the relationship between the total system and local pathological
      processes in patients with grave combined thoracic injuries and analysis of the
      efficacy of various therapeutic measures included in the intensive care complex
      brought the authors to a conclusion about the efficacy of surgical interventions,
      including repair of the thoracic carcass, in the early periods after the injury.
      They claim that artificial ventilation of the lungs is permitted, if necessary,
      during a limited period, and an intervention should be performed as early as
      possible in order to attain the recovery of spontaneous respiration.

PMID- 9027251
TI  - [The utilization of nutrient substances during wound healing].
AB  - The process of wound healing represents a series of complex physicochemical
      reactions requiring different nutritional microcomponents at each stage. In
      patients with extremely grave diseases and injuries the course of wound healing
      is impaired because of a hypermetabolic reaction to stress, leading to protein
      catabolism. The hypothalamus responds to cytokine stimulation by changes of
      thermoregulation (increase of heat production) and increased production of stress
      hormones (catecholamines, hydrocortisone, and glucagon). In turn, stress hormones
      trigger the thermogenous (unproductive) metabolic cycle and the lipolysis and
      proteolysis processes. Hyperproduction of glucose at the expense of skeletal
      muscle tissue degradation leads to the formation of amino acid substrate for
      liver glyconeogenesis. Additional nutrients are obligatory for wound healing in
      such patients. Protein catabolism cannot be arrested by amino, acids alone partly
      because amino acid transport is impaired; it can be normalized by anabolics, such
      as growth hormone and insulin-like growth factor 1. Treatment with growth hormone
      yields a dramatic positive effect in severely burned children. Proteins and
      vitamins, specifically arginine and vitamins A, B, and C provide the optimal
      nutritive support during wound treatment.

PMID- 9027252
TI  - [The efficacy of Capoten in different clinical courses of acute myocardial
      infarct].

PMID- 9027253
TI  - [The old and eternally new problems of resuscitation].

PMID- 9027255
TI  - [Changes in the functional status of the left-ventricular myocardium during dying
      and in the early postresuscitation period].
AB  - Experiments on dogs have shown that left-ventricular contractility reduces and
      the processes of contraction and relaxation are discoordinated during the first
      minutes of dying from acute blood loss with the mean arterial pressure of 40 mm
      Hg. During the postreanimation period following a ten-min clinical death
      spontaneous respiration is resumed late (after 15.1 +/- 3.2 min), as are the
      corneal reflexes (after 46.1 +/- 8.5 min). If there are no changes in left
      ventricular contractility in the course of dying, vital functions of the organism
      and neurological reflexes recover sooner (respiration after 6.1 +/- 2.0 min and
      corneal reflexes after 32.6 +/- 4.1 min). A relationship has been revealed
      between the severity of the postreanimation period and the degree of reduction of
      left-ventricular myocardial contractility during hypoperfusion (1 to 6 hrs after
      reanimation): the contractility index in animals with late neurologic recovery
      was lower than in those with a relatively early neurologic recovery.

PMID- 9027254
TI  - [Disordered cardiac contractility after clinical death caused by acute blood
      loss].
AB  - The regularities of development of postresuscitation cardiodepression were
      studied in experiments on outbred male rats resuscitated after 4-min clinical
      death from acute blood loss. The studies were carried out for the whole organism,
      isolated isovolumetrically contracting heart, and for the isolated papillary
      muscle. As a result of acute critical blood loss, the functional reserve of the
      myocardium dropped and fatigue rapidly developed, progressing to asystole and
      fibrillation during the maximal exercise. Cardiodepression was expressed most of
      all during the first day, particularly during the first hours after
      resuscitation. Later the contractility gradually normalized, and 3 months after
      resuscitation it did not reliably differ from the control. The disorders involved
      the relaxation processes most of all.

PMID- 9027256
TI  - [The verapamil correction of postresuscitation damages to the heart].
AB  - Disorders of systemic hemodynamics and myocardial contractility during the early
      postresuscitation period were examined in 132 outbred male rats resuscitated
      after 4-min clinical death from acute blood loss. The efficacy of adding
      verapamil (calcium ion antagonist) in a dose of 0.1 mg/kg to a complex of
      reanimation measures was assessed. Verapamil added to resuscitation procedures
      was conducive to an earlier repair of heart work and to a reduction of the early
      postresuscitation arrhythmias; it ensured a hemodynamic relief of the heart and
      decreased cardiodepression. Cardioprotective effect of verapamil was due to its
      ability to protect cell membranes from irreversible ischemic and reperfusion
      damage by preventing the postresuscitation calcium overloading of cardiomyocytes.

PMID- 9027257
TI  - [The neurochemical, molecular and ultrastructural mechanisms of the formation of
      latent postresuscitation encephalopathy].
AB  - The content of total RNA and DNA, activity of Ca2+, Mg(2+)-dependent DNA
      endonuclease, and ultrastructural changes in nerve tissue cells were examined in
      the brain cortex of narcotized dogs 1 to 3 months after a 4-hour hemorrhagic
      shock (arterial pressure 40 mm Hg). A new variant of reconstruction of cell
      membranes and organelles formed by them was revealed, developing in the brain
      neurons in the course of adaptation during the first-third months of the
      postshock period. Evidently, the molecular base of development of an atypical
      variant of cell structure rearrangement in the remote period after shock is the
      internucleosomal fragmentation of a part of the DNA of nerve cells resultant from
      DNA endonucleolysis and subsequent information disintegration of a cell as a
      system. This distorts the process of biosynthesis of supramolecular ensembles,
      specifically, of nerve cell biomembranes.

PMID- 9027258
TI  - [The interneuronal correlations in the cerebellar cortex in the postresuscitation
      period].
AB  - Quantitative analysis of the neuronal populations of the cerebellar cortex was
      carried out in white rats after reanimation. Clinical death was modeled by 10-min
      clamping of the neurovascular plexus near the heart. The material for analysis
      was collected at the end of ischemia, 90 min, 1, 3, and 7 days after it. There
      are about 8 neurons of the molecular layer and 250 granular cells per pyramidal
      neuron in an intact cerebellar cortex of white rats. Staring from day 3 of the
      postreanimation period, the number of granular cells per pyramidal neuron
      increases, whereas the ratio of the molecular layer neurons and pyramidal neurons
      differs but negligibly from the control values over the entire follow-up period.
      Different sensitivity of various neuron populations to an ischemic exposure leads
      to the formation of the structural basis for the predominance of stimulating
      pulsation in the cerebellar cortex and reduces its inhibitory effect on the
      cerebellar nucleus in the postreanimation period.

PMID- 9027259
TI  - [Postresuscitation changes in the nitric-oxide synthase activity and radical
      formation in sections of the rat brain].

PMID- 9027260
TI  - [The effect of succinic acid on postresuscitation pathology of the CNS and of the
      body as a whole].
AB  - The effect of oral succinic acid was studied in rats exposed to 10-min heart
      arrest followed by resuscitation. The drug was administered for 5 days in a dose
      of 30 mg/kg starting from day 3 up to day 7 after resuscitation. Succinic acid
      was found to normalize the orientation and exploration behavior of rats in the
      "open field" test, decreased the intensity of response to stress (electric
      shock), and normalized the radical formation in the brain tissue and blood serum,
      thus reducing the morphological changes in the brain. In addition, succinic acid
      prevented the development of risk factors of atherogenesis, namely, increase of
      the levels of blood cholesterol, triglycerides, and low and very low density
      lipoproteins. Further studies are needed to validate the addition of succinic
      acid to the armory of drugs preventing the development of postresuscitation
      encephalopathies in remote (3 months) periods.

PMID- 9027261
TI  - [The hyperbaric oxygen therapy of disordered ammonia detoxication in the operated
      liver].
AB  - The status of the main routes of ammonium detoxication in the liver (synthesis of
      glutamine and urea) after its resection and hyperbaric oxygenation (HBO) was
      studied in 160 rats. HBO (3 sessions at 3 atm. abs.--50 min) following resection
      of the liver stimulated the activity of glutamine synthase and prevented the
      reduction of glutamate (a substrate for glutamine synthesis) level in the
      operated on liver. Hyperbaric oxygen activated the glutamine-dependent and non
      glutamine-dependent pathways of urea synthesis in the resected liver and ensured
      the incorporation of glutamine amido groups in the ornithine cycle. HBO boosted
      the inhibitory effect of liver resection on the activity of glutamate
      dehydrogenase and prevented the accumulation of ammonium in the hepatocytes of
      resected liver. The stimulating effect of HBO on the ammonium-detoxifying
      function of the resected liver persisted for 11 days after the exposure.

PMID- 9027262
TI  - [The potentials for therapy of the postresuscitation process using regulatory
      peptides after 10 and 15 minutes of heart arrest].
AB  - The therapeutic effect of a single systemic injection of regulatory peptides was
      assessed in experiments oil white rats exposed to 10- and 15-min heart arrest.
      The effect of regulatory peptides was found to depend on the initial body
      resistance to hypoxia and on the duration of heart arrest. Positive effects of
      thyrotropin-releasing factor, ACTH4-10 and substance P on the recovery of
      cerebral function grew weaker as the duration of heart arrest increased, whereas
      the effects of oxitocin and somatostatin were unchanged, and that of taftsin even
      increased. In animals nonresistant to hypoxia cardiopulmonary resuscitation and
      survival of 50% of animals after 15-min heart arrest was provided by injection of
      thyrotropin-releasing factor at the beginning of resuscitation and of
      somatostatin 30 min later.

PMID- 9027264
TI  - [The simplest methods for controlling patient status in resuscitation and
      intensive therapy units].

PMID- 9027263
TI  - [Intensive therapy and cardiopulmonary resuscitation in the sudden cessation of
      efficient cardiac activity].

PMID- 9027265
TI  - [A universal perfusion headpiece for hemosorption and a variant of its attachment
      to flasks].

PMID- 9027266
TI  - [Fibrillation of the heart ventricles].
AB  - During ventricular fibrillation, extra feedback may form in the myocardial
      structure due to specific features of such fibrillation, specifically, because of
      highly asynchronous contractions of some parts of the myocardium; these newly
      forming feedback is conducive to a persistent development of such arrhythmia. The
      frequency of the waves of mechanical contractions in various segments of the
      myocardium varies depending on the increase of hypoxia. The waves do not
      correlate with each other as regards their shape, neither do they correlate with
      the electrical activity waves. This indicates the complex nature of the
      mechanisms giving rise to and maintaining ventricular fibrillation. Study of the
      electromechanical correlations in the myocardium, observed in ventricular
      fibrillation, and analysis thereof together with the complex staged development
      of ventricular fibrillation may help better understand the pathological processes
      in the myocardium and, hence, enable us to develop effective methods to control
      it.

PMID- 9027267
TI  - Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to
      moderate asthma. A randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: The increasing costs of managing asthma are due in part to the
      introduction of new medications, such as leukotriene receptor antagonists. These
      antagonists interfere with the action of leukotrienes, which are implicated in
      bronchoconstriction and the formation of airway edema in patients with asthma.
      Leukotriene receptor antagonists must be shown to be clinically and economically
      effective for their clinical use to be justified. OBJECTIVE: To assess the
      clinical and economic effectiveness of zafirlukast, a leukotriene receptor
      antagonist, in patients with mild-to-moderate asthma who might benefit from
      regular anti-inflammatory therapy. DESIGN: Randomized, double-blind, multicenter,
      placebo-controlled trial. SETTING: 28 outpatient clinics. PATIENTS: 146 patients
      with mild-to-moderate asthma who were 12 years of age or older, had not smoked
      cigarettes in the previous 6 months, had a smoking history of less than 10 pack
      years, had an FEV1 at least 55% of the predicted value with no upper limit, had
      demonstrated bronchial hyperresponsiveness, and were symptomatic during the 7-day
      run-in period. All patients were seen every 2 to 3 weeks for 13 weeks.
      INTERVENTION: 103 patients received zafirlukast (20 mg twice daily), and 43
      patients received placebo (twice daily). All patients received inhaled beta
      agonists as needed. MEASUREMENTS: Data were obtained from medical examinations,
      patient questionnaires, and daily diaries. The clinical effectiveness outcomes
      were days per month without asthma symptoms, limitation of activity, use of beta
      agonists, sleep disturbance, and episodes of asthma (the latter was a composite
      measure made up of the first four outcomes plus the occurrence of adverse
      events). The economic effectiveness outcomes were frequency and type of
      unscheduled health care contacts, use of beta-agonist inhalers, consumption of
      nonasthma medications, and days of absence from work or school. RESULTS: The
      zafirlukast group had 89% more days without symptoms (adjusted rates, 7.0
      compared with 3.7 days per month; P = 0.03), 89% more days without use of beta
      agonists (adjusted rates, 11.3 compared with 6.0 days per month; P = 0.001), and
      98% more days without episodes of asthma (adjusted rates, 10.1 compared with 5.1
      days per month; P = 0.003). They also had 55% (95% CI, 19% to 74%) fewer health
      care contacts (18.5 compared with 40.7 per 100 per month; P = 0.007) and 55% (CI,
      3% to 79%) fewer days of absence from work or school (15.6 compared with 35.0 per
      100 per month; P = 0.04). They used 17% fewer canisters of inhaled beta-agonists
      (P = 0.17) and 19% less nonasthma medication (P < 0.2). CONCLUSIONS: A daily
      regimen of zafirlukast added to as-needed inhaled beta-agonists is more effective
      than beta-agonists alone in treating mild-to-moderate asthma. The clinical and
      economic effectiveness of zafirlukast, a potential alternative to inhaled
      corticosteroids, provides further impetus to use regular "preventive" therapy in
      patients with mild-to-moderate asthma.

PMID- 9027268
TI  - Health and functional status of long-term survivors of bone marrow
      transplantation. EBMT Working Party on Late Effects and EULEP Study Group on Late
      Effects. European Group for Blood and Marrow Transplantation.
AB  - BACKGROUND: Although many patients now survive the short-term complications of
      bone marrow transplantation for life-threatening hematologic disease, information
      on the health and activity of long-term survivors is sparse. OBJECTIVE: To
      evaluate the morbidity and mortality of patients surviving more than 5 years
      after allogeneic bone marrow transplantation. DESIGN: Retrospective, multicenter
      study. PATIENTS: 798 recipients of bone marrow transplants (477 adults, 321
      children) from 43 European centers. Patients had received transplants before
      December 1985 and had survived at least 5 years. Patients had received allogeneic
      or syngeneic bone marrow for leukemia, lymphoma, inborn diseases of the
      hematopoietic and immune systems, and severe aplastic anemia. MEASUREMENTS:
      Survival, clinical performance according to Karnofsky score (in increments of
      10%), and social reintegration were assessed as outcomes. Patient age and sex,
      primary disease and status at transplantation, histocompatibility of the donor,
      conditioning regimen, type of prophylaxis of graft-versus-host disease, and acute
      and chronic graft-versus-host disease were evaluated as variables. RESULTS: For
      the 55 5-year survivors, actuarial mortality was 8% at 10 years and 14% at 15
      years. The leading causes of death were disease recurrence (21 patients), chronic
      graft-versus-host disease with complicating infections and lung disease (11
      patients), secondary cancer (8 patients), and the acquired immunodeficiency
      syndrome (AIDS) (5 patients). When patients with recurrent disease were excluded,
      late death was associated with chronic graft-versus-host disease (P < 0.001),
      occurrence of secondary cancer (P < 0.001), male sex of the patient (P = 0.05),
      and female sex of the donor (P = 0.002). Clinical performance was normal
      (Karnofsky score, 100%) or minimally reduced (Karnofsky score, 90%) in 93% of
      patients; 89% of patients resumed full-time work or school. Reduced performance
      status and incomplete resumption of social activity were associated with chronic
      graft-versus-host disease, recurrent leukemia, AIDS, secondary cancer, organ
      dysfunction, and neurologic or psychological problems. Other risk factors for
      incomplete resumption of social activity were female sex (P = 0.002) and older
      age at transplantation (P = 0.001). CONCLUSIONS: More than 5 years after bone
      marrow transplantation, most patients were in good health (93%) and had returned
      to full-time work or school (89%). Recurrence of the primary disease, secondary
      cancer, and chronic graft-versus-host disease and its sequelae remain problems
      for some patients.

PMID- 9027269
TI  - Parenteral ketorolac: the risk for acute renal failure.
AB  - BACKGROUND: Acute renal failure has been associated with parenteral ketorolac
      tromethamine, but the risk that is associated with this therapy has not been
      quantified. OBJECTIVE: To compare the risk for acute renal failure associated
      with ketorolac with that associated with opioids. DESIGN: Retrospective cohort
      study. SETTING: 35 hospitals in or near Philadelphia. PATIENTS: Patients
      receiving 10,219 courses of parenteral ketorolac and patients receiving 10,145
      courses of parenteral opioids. MEASUREMENTS: Acute renal failure was defined by
      1) an increase in the serum creatinine concentration of 50% or more and 2) either
      an absolute increase of 44.2 mumol/L or more for concentrations that were less
      than 132.6 mumol/L at baseline or an absolute increase of 88.4 mumol/L or more
      for concentrations that were 132.6 mumol/L or more at baseline. In addition, a
      secondary definition required a diagnosis by a physician. RESULTS: The overall
      incidence of acute renal failure was 1.1% after therapy with either ketorolac or
      opioids. Multivariate-adjusted rate ratios comparing ketorolac with opioids for
      acute renal failure were 1.09 (95% CI, 0.83 to 1.42) overall, 1.00 (CI, 0.76 to
      1.33) for less than 5 days of therapy, and 2.08 (CI, 1.08 to 4.00; P = 0.03) for
      more than 5 days of therapy. Similar results were obtained when the secondary
      definition of acute renal failure was used. CONCLUSIONS: Overall, acute renal
      failure was uncommon in this hospitalized population. Compared with opioids,
      ketorolac administered for 5 days or less did not increase the rate of renal
      failure. However, among patients who were treated with analgesics for more than 5
      days, ketorolac may be associated with an elevated rate of acute renal failure.

PMID- 9027270
TI  - Cardioversion guided by transesophageal echocardiography: the ACUTE Pilot Study.
      A randomized, controlled trial. Assessment of Cardioversion Using Transesophageal
      Echocardiography.
AB  - BACKGROUND: Electrical cardioversion in patients with atrial fibrillation is
      associated with an increased risk for embolic stroke. Screening for atrial
      thrombi with transesophageal echocardiography (TEE) before cardioversion should,
      in many patients, safely permit cardioversion to be done earlier than would be
      possible with prolonged conventional, anticoagulation therapy. OBJECTIVE: To
      compare the feasibility and safety of TEE-guided early cardioversion with those
      of conventional management of cardioversion in patients with atrial fibrillation.
      DESIGN: Randomized, multicenter clinical trial. SETTING: 10 hospitals in the
      United States, Europe, and Australia. PATIENTS: 126 patients who had atrial
      fibrillation lasting longer than 2 days and were having electrical cardioversion.
      INTERVENTION: Conventional therapy or early, TEE-guided cardioversion with short
      term anticoagulation therapy. OUTCOME MEASURES: Feasibility outcome variables
      were frequency of cardioversion and times to cardioversion and sinus rhythm.
      Safety outcomes were ischemic stroke, transient ischemic attack, systemic
      embolization, bleeding, and detected episodes of clinical hemodynamic instability
      occurring as long as 4 weeks after cardioversion. RESULTS: 62 patients were
      randomly assigned to receive TEE-guided cardioversion; TEE was done in 56 (90%)
      of these patients. Atrial thrombi were detected in 7 patients (13%) and led to
      the postponement of cardioversion. Cardioversion was successful in 38 of 45
      patients (84%) who had early cardioversion. No embolization occurred with this
      strategy. Of the 64 patients receiving conventional therapy, 37 (58%) had
      cardioversion, which was successful in 28 patients (76%). One patient had a
      peripheral embolic event. The time to cardioversion was shorter in the TEE group
      (0.6 weeks [95% CI, 0.3 to 0.9 weeks] compared with 4.8 weeks [CI, 3.8 to 5.7
      weeks]; P < 0.01). The incidence of clinical hemodynamic instability and bleeding
      complications tended to be greater in the conventional therapy group.
      CONCLUSIONS: These results suggest that TEE-guided cardioversion with short-term
      anticoagulation therapy is feasible and safe. The use of TEE may allow
      cardioversion to be done earlier, may decrease the risk for embolism associated
      with cardioversion, and may be associated with less clinical instability than
      conventional therapy. A large, multicenter study to confirm these findings is
      currently under way.

PMID- 9027271
TI  - Reliability of tuberculin skin test measurement.
AB  - BACKGROUND: Important management decisions depend on results of the tuberculin
      skin test. However, the test is subject to several potential errors, and its
      reliability has not been adequately studied. OBJECTIVE: To ascertain the
      reliability of tuberculin skin testing. DESIGN: Cross-sectional study. SETTING:
      University hospital. PARTICIPANTS: 96 persons who received a tuberculin skin
      test. MEASUREMENTS: Ballpoint-pen and palpation measures of induration. RESULTS:
      Global intra- and interobserver reliability coefficients of the ballpoint-pen
      technique were high. Five percent of the time, however, a second measurement by
      the same observer could be at least 2.7 mm less to 3.0 mm more than the first
      measurement and the measurement from the second observer could be at least 3.4 mm
      less to 3.7 mm more than the measurement from the first observer. This could lead
      to the reclassification of a positive test result as negative or vice versa. The
      area of imprecision was 38% less broad for the ballpoint-pen technique than for
      the palpation technique. CONCLUSION: Reading of tuberculin skin tests may
      frequently result in misclassifications when measurements are close to the cutoff
      point that separates negative from positive results.

PMID- 9027272
TI  - Cardiac Whipple disease: identification of Whipple bacillus by electron
      microscopy of a patient before death.

PMID- 9027273
TI  - On bedside teaching.
AB  - Actual teaching at the bedside during attending rounds, with emphasis on history
      taking and physical diagnosis, has declined from an incidence of 75% in the 1960s
      to an incidence of less than 16% today. Profound advances in technology, in
      imaging, and in laboratory testing and our fascination for these aspects of
      patient care, account for part of this decline, but faculty must also assume
      responsibility for the present lack of bedside teaching. If we are to reverse
      this trend, we will need to realize the barriers to bedside teaching, both real
      and imagined, and overcome them. And if we are to become effective bedside
      teachers, as were our mentors, we will need to sharpen our own physical
      diagnostic skills. We will need to learn how to be gentle with students and
      housestaff, how to better communicate with patients, and how to teach ethics and
      professionalism with the patient at hand.

PMID- 9027274
TI  - Update in gastroenterology.

PMID- 9027275
TI  - Thyroid incidentalomas: management approaches to nonpalpable nodules discovered
      incidentally on thyroid imaging.
AB  - BACKGROUND: The introduction of highly sensitive imaging techniques has made it
      possible to detect many non-palpable nodules, or "incidentalomas," in the
      thyroid. Discovery of these lesions raises concerns about their malignancy, but
      the optimal strategy for managing these lesions has not been clearly established.
      PURPOSE: To review evidence about incidentalomas, including prevalence and risk
      for malignancy, and to provide recommendations for their evaluation and
      treatment. DATA SOURCES: Literature searches for relevant articles published in
      the past 15 years in major English-language medical journals, review of selected
      articles published before this period, and reviews of bibliographies in text
      books. STUDY SELECTION: Three studies on autopsy findings, 11 studies on
      ultrasonographic findings, and other reports on nonpalpable thyroid nodules were
      included. DATA EXTRACTION: Data on the prevalence of nodules on autopsy and in
      ultrasonographic series, palpation compared with ultrasonography, the risk for
      malignancy in nodules found in irradiated glands, the natural history of thyroid
      nodules, and the prevalence of occult cancer were collated and reviewed. DATA
      SYNTHESIS: Prevalence of thyroid incidentalomas estimated from autopsy studies
      ranges from 30% to 60%. Studies comparing clinical palpation with thyroid imaging
      show a prevalence of 13% to 50%. Prospective studies of randomly selected
      patients have reported a prevalence of 19% to 67%. The risk for malignancy in
      asymptomatic nodules found in nonirradiated glands is 0.45% to 13% (mean +/- SD,
      3.9% +/- 4.1%). CONCLUSIONS: High-resolution ultrasonography is sensitive and
      capable of detecting many small, nonpalpable thyroid nodules. Most of these
      lesions are benign. For most patients with nonpalpable nodules that are
      incidentally detected by thyroid imaging, simple follow-up neck palpation is
      sufficient.

PMID- 9027276
TI  - Inefficacy of allopurinol as monotherapy for Colombian cutaneous leishmaniasis. A
      randomized, controlled trial.
AB  - BACKGROUND: Hundreds of thousands of cases of cutaneous leishmaniasis occur each
      year worldwide. Available therapies are parenteral, moderately toxic, and costly.
      OBJECTIVE: To determine the efficacy of and tolerance for oral allopurinol as
      monotherapy for cutaneous leishmaniasis. DESIGN: Randomized, controlled trial.
      SETTING: Outpatient clinics in 11 regions of Colombia in which cutaneous
      leishmaniasis is endemic. PATIENTS: 187 otherwise healthy adults with cutaneous
      leishmaniasis. Eighty-four percent of patients were infected with or were from
      regions with Leishmania panamensis; 16% were infected or were from regions with
      L. braziliensis. INTERVENTION: Patients were randomly assigned to one of three
      treatment groups. The first group received allopurinol, three 100-mg tablets four
      times daily (20 mg/kg of body weight per day) for 28 days. The second group
      received three placebo tablets four times daily for 28 days. The third group
      received Glucantime, 20 mg of intramuscular antimony/kg per day for 20 days.
      MEASUREMENT: Complete cure was defined as complete clinical reepithelialization
      of all lesions at 3 months and no relapse during 12 months of follow-up. RESULTS:
      Of 182 patients whose data could be analyzed, 157 (86%) were evaluated. In the
      allopurinol group, 18 of 55 (33% [95% CI, 21% to 47%]) patients were cured; in
      the placebo group, 17 of 46 patients (37% [CI, 23% to 52%]) were cured
      (difference, 4% [CI, -14% to 22%]; P = 0.68); and in the Glucantime group, 52 of
      56 patients (93% [CI, 83% to 98%]) were cured (P < 0.001 compared with the
      allopurinol and placebo groups combined). In most cases, therapy was considered
      to have failed because the lesion did not reepithelialize by 1.5 months after the
      end of therapy. Three cases of relapse (two in the allopurinol group and one in
      the placebo group) at the nasal mucosa (mucosal leishmaniasis) had occurred by
      the end of 12 months of follow-up. CONCLUSIONS: Allopurinol monotherapy has no
      effect on Colombian cutaneous disease primarily caused by L. panamensis and
      therefore is unlikely to be effective against cutaneous leishmaniasis in other
      endemic regions.

PMID- 9027277
TI  - Tuberculosis then and now: a personal perspective on the last 50 years.
AB  - Rates of death from tuberculosis in the United States decreased from 194 per
      100,000 persons in 1900 to 40 per 100,000 persons in 1945, in part because the
      epidemic of tuberculosis in the western world was running its course and in part
      because of public health initiatives and improved socioeconomic conditions. In
      1945, 63,000 persons died of tuberculosis and 115,000 new cases of the disease
      emerged. Streptomycin and para-aminosalicylic acid had just been discovered; the
      discovery of isoniazid followed, in 1952. Sanitarium care, nonsurgical and
      surgical collapse therapy, and resectional surgery were in widespread use. By the
      middle of the 1950s, it was evident that bedrest did not add to the benefit
      produced by effective chemotherapy, and sanitariums began to close, a process
      that was completed by the 1970s. As mortality and morbidity due to tuberculosis
      rapidly decreased, the U.S. government decreased funding for tuberculosis and
      many states and cities downgraded their tuberculosis control programs. After
      1984, the rate of new cases of tuberculosis, which had decreased to 9.4 per
      100,000, began to increase and focal outbreaks of multidrug-resistant
      tuberculosis were reported. Noncompliance with drug therapy, homelessness,
      immigration to the United States from developing countries, and human
      immunodeficiency virus (HIV) infection were invoked as explanations. With the
      reinstitution of federal funding, improved case-finding and surveillance, and the
      practice of having patients receive therapy while under direct observation, the
      rate of new cases of tuberculosis decreased to 8.7 per 100,000 in 1995, the
      lowest rate since national surveillance was begun in 1953. However, at the end of
      the 20th century, the worldwide burden of tuberculosis, which is engrafted onto
      the pandemic of HIV infection, is enormous: an estimated 7.6 million new cases in
      developing countries and 400,000 new cases in industrial nations.

PMID- 9027278
TI  - Management of atrial fibrillation: simplicity surrounded by controversy.

PMID- 9027279
TI  - Doing the little things.

PMID- 9027280
TI  - Pennyroyal metabolites in human poisoning.

PMID- 9027281
TI  - Ethics, mandated choice, and organ donation.

PMID- 9027282
TI  - Race and ethnicity: a compelling research agenda.

PMID- 9027283
TI  - Physician-run health plans and antitrust.

PMID- 9027284
TI  - [Medical microbial ecology: current status and outlook].

PMID- 9027285
TI  - [Outlook for using bacteria of the genus Bacillus for the design of new
      biopreparations].
AB  - The data evident of the promising use of Bacillus as a basis of new probiotics
      are presented. The criteria of the Bacillus screening among the other
      representatives of the exogenic microflora provided the design of a probiotic,
      named biosporin, which markedly differed from the other biological preparations
      based on aerobic sporulating bacteria. Biosporin proved to be an efficient agent
      in the treatment of acute intestinal infection due to pathogenic and
      opportunistic bacteria as well as in the treatment of dysbacteriosis of various
      etiology. A principally new probiotic, named subalin, with antibacterial and
      antiviral properties was designed on the basis of biosporin by the gene
      engineering. The data on the promising use of Bacillus in the composition of
      complex probiotics are also presented.

PMID- 9027286
TI  - [Change in various biological properties of Lactobacillus as affected by
      ribonuclease].
AB  - The influence of RNAse from Bacillus intermedius on the growth of the industrial
      strain Lactobacillus plantarum 8R-A3 was studied. It was shown that the
      stimulating effect of the enzyme depended on its dose and manifested itself in
      decreasing the growth lag phase. At the same time the growth stimulating dose of
      RNAse increased the Lactobacillus adhesion to the epithelial cells and promoted
      secretion of proteinases from Lactobacillus to the culture medium. The possible
      use of RNAse as a stimulant of the growth of industrial strains was demonstrated
      which is advantageous for colonization of the biological surfaces.

PMID- 9027287
TI  - [Development of technology for isolation and purification of gentamicin using
      sorption without filtration].
AB  - A technology for isolation and purification of gentamicin from nonfiltered
      fermentation broth with the use of sorption-pulsory columns was developed as a
      result of the research work. The practical application of the technology will
      increase the yield from 30 to 57 per cent and reduce the content of the minor
      admixtures in the final product up to 5 per cent in comparison to the currently
      used process.

PMID- 9027288
TI  - [Comparison of the results of determining antibiotic sensitivity on AGV medium
      and on Mueller-Hinton and isosensitest agars].
AB  - To evaluate the adequacy of AGV agar for antimicrobial susceptibility testing,
      the susceptibility of a range of bacteria to 10 antimicrobials on AGV, Mueller
      Hinton and isoSensitest agars, all supplemented with 5 per cent lyzed horse blood
      was determined. Disc tests were used. In general, AGV agar gave identical
      susceptibility results to Mueller-Hinton and isoSensitest agars for common gram
      positive and gram negative bacteria with most of the tested microbials excluding
      sulphonamides and trimethoprim. With those latter antimicrobials inhibition zones
      for susceptible organisms were not formed on AGV agar whereas large zones were
      present on Mueller-Hinton and isoSensitest agars. This discrepancy probably can
      be explained by the presence of high levels of thymidine in AGV agar; too high to
      be corrected even by the addition of 5 per cent lysed horse blood. AGV agar is
      possible to use for susceptibility testing with most of the microbials excluding
      trimethoprim and sulphonamides.

PMID- 9027289
TI  - [Effectiveness of the treatment of staphylococcal pneumonia with liposomal
      gentamicin in an experiment].
AB  - An in vivo comparative study on penetration of free gentamicin sulfate and
      liposome-entrapped gentamicin sulfate to macrophages was performed and the
      efficacy of the treatment of destructive pneumonia was estimated on albino mice.
      The liposome-entrapped antibiotic was arrested by the cells of the mononuclear
      phagocytic system thus providing higher concentrations of the drug in the organs
      with high counts of macrophages, the antibiotic retention time in the organs
      being longer than that after the use of free gentamicin. The use of liposome
      entrapped gentamicin in the treatment of destructive pneumonia made it possible
      to increase the host protection from 17 to 50 per cent.

PMID- 9027290
TI  - [Freedom of thought and optimism. On the 80th anniversary of the death of I. I.
      Mechnikov].

PMID- 9027291
TI  - [Enterotoxigenicity of gram-negative microorganisms isolated from the region of
      congenital cleft palate in children].
AB  - One hundred and ninety four stains of opportunistic gram negative bacteria were
      isolated from 106 children with congenital cleft palate. 83 of them (42.7 per
      cent) reduced enterotoxin. For comparison, microflora of the oral cavity in 32
      healthy children was investigated and 40 strains of opportunistic gram negative
      organisms were isolated. Only 3 of them proved to be enterotoxigenic. Therefore,
      the frequency of the enterotoxigenic bacteria in the children with cleft palate
      was higher than that in the healthy children.

PMID- 9027292
TI  - [Comparative characterization of the sensitivity of regional strains of various
      microorganisms to cefuroxime and other antibiotics].

PMID- 9027293
TI  - [Role of prophages in the formation of antibiotic-resistant populations of
      Staphylococcus in the process of transformation, transduction and conjugation].

PMID- 9027294
TI  - Australian quality assurance leads the way.

PMID- 9027295
TI  - Gene technology will make fruit and vegetables the key to public health.

PMID- 9027296
TI  - Triple therapy reduces HIV virus to undetected levels.

PMID- 9027297
TI  - Lateral cervical spine films in Down syndrome.

PMID- 9027298
TI  - Presynaptic bodies ("ribbons"): from ultrastructural observations to molecular
      perspectives.
AB  - The morphological diversity and dynamic aspects of presynaptic bodies are
      summarised. Molecular characteristics of the presynaptic machinery are discussed
      and the signals that control the plasticity of the presynaptic bodies are
      examined. A review is presented of recent findings regarding the physiology of
      tonically active synapses. The significance of the synaptic bodies and their
      dynamic changes in retinal and pineal photoreceptors are considered.

PMID- 9027299
TI  - Immunocytochemical analysis of glomerular regionalization and neuronal diversity
      in the olfactory deutocerebrum of the spiny lobster.
AB  - Antibodies against serotonin, dopamine, FMRF amide, substance P, and molluscan
      small cardioactive peptide (SCPB) were used to differentiate glomeruli and
      neurons in the olfactory deutocerebrum of the spiny lobster, Panulirus argus.
      Immunoreactivity to these antibodies identified distinct regions within
      individual columnar glomeruli of the olfactory lobe (OL), but not within the
      spherical glomeruli of the accessory lobe (AL). Glomeruli in the lateral,
      central, and medial layers of the AL, however, had different patterns of
      immunoreactivity. The immunostainings differentiated six types of local
      interneurons and three types of centrifugal projection neurons. Local
      interneurons included: (1) a "dorsal giant" neuron with serotonin- and FMRF amide
      like immunoreactivity arborizing in most or all glomeruli of the OL, in the
      glomeruli of the medial and lateral layer of the AL and in the unstructured
      olfactory globular tract neuropil, (2) three large OL "core" neurons, two with
      serotonin-like and one with FMRF amide-like immunoreactivity innervating many OL
      glomeruli, (3) several hundred small, globuli-type OL "core" neurons with
      serotonin- and FMRF amide-like immunoreactivity, (4) thousands of small, globuli
      type neurons with FMRF amide- and/or substance P-like immunoreactivity connecting
      the OL with the central layer of the AL, (5) thousands of small, globuli-type AL
      interneurons with substance P like immunoreactivity and additional arborizations
      in the unstructured deutocerebral tract neuropil, and (6) many small, globuli
      type OL "rim" neurons with FMRF amide- and/or SCPB-like immunoreactivity.
      Centrifugal projection neurons included two that targeted the soma clusters and a
      pair of large neurons with dopamine-like immunoreactivity that originated in the
      lateral protocerebrum and arborized in the OL and AL glomeruli. Only few
      ascending projection neurons and no olfactory afferents were labeled. These
      results suggest that in the spiny lobster neurochemically distinct subpopulations
      of local interneurons constitute functionally distinct regions within individual
      OL glomeruli and across groups of AL glomeruli. 

PMID- 9027300
TI  - Enzyme histochemical characteristics of osteoblasts and mononucleated osteoclasts
      in a teleost fish with acellular bone (Oreochromis niloticus, Cichlidae).
AB  - Bone resorption by mononucleated cells was studied in the acellular bone of a
      teleost fish (Oreochromis niloticus) by histological and enzyme histochemical
      observations and by transmission electron microscopy. Bone resorbing cells
      (osteoclasts) were identified by their location at the sites of bone resorption,
      their frequent association with a band of concentrated activity of tartrate
      resistant acid phosphatase at the bone surface and by the presence or lack of
      certain enzymes. Tartrate-resistant acid phosphatase was used as a marker for
      osteoclasts, and alkaline phosphatase as a marker for osteoblasts. Osteoclasts in
      O. niloticus are not multinucleated; however, during intense bone resorption,
      they form cell aggregations that resemble multinucleated giant cells in mammals.
      Conversely, during less intense bone degradation, osteoclasts are flat, have long
      narrow cytoplasmic processes and resemble the bone-lining cells of mammals. All
      bone-resorbing cells in O. niloticus are mononucleated and lack a ruffled border.
      Similarities to and differences from bone resorption by mononucleated cells in
      mammals are discussed. 

PMID- 9027303
TI  - A Unified Theory Based on SO(5) Symmetry of Superconductivity and
      Antiferromagnetism
AB  - The complex phase diagram of high-critical temperature (Tc) superconductors can
      be deduced from an SO(5) symmetry principle that unifies antiferromagnetism and d
      wave superconductivity. The approximate SO(5) symmetry has been derived from the
      microscopic Hamiltonian, and it becomes exact under renormalization group flow
      toward a bicritical point. This symmetry enables the construction of a SO(5)
      quantum nonlinear final sigma model that describes the phase diagram and the
      effective low-energy dynamics of the system. This model naturally explains the
      basic phenomenology of the high-Tc superconductors from the insulating to the
      underdoped and the optimally doped region.

PMID- 9027301
TI  - Simultaneous restitution of matrix and cells in gastric ulcer: use of a combined
      in-situ hybridization and immunohistochemistry technique applicable to paraffin
      embedded tissue.
AB  - The restoration of gastric tissue after ulceration involves cellular and matrix
      components. Our aim was to investigate the kinetics of collagen expression and
      cellular proliferation in an animal model of gastric ulcer. To demonstrate the
      expression of type I and IV collagen mRNAs by proliferating cells, a method
      combining in-situ hybridization and immunohistochemistry was devised. In order to
      avoid the disadvantages of radioisotopes, digoxigenin-labeled RNA-riboprobes were
      utilized and combined with single-step immunohistochemistry. This method proved
      sensitive enough to detect type I and IV procollagen mRNA transcripts in the
      submucosal area beneath the ulcer crater or adjacent to the ulcer rim. In
      addition, a subset of cells transcribing either procollagen type I or IV RNA was
      concomitantly positive for proliferating cell nuclear antigen by
      immunohistochemistry. Focal proliferation of cells simultaneously expressing
      extracellular matrix components may therefore occur in the gastric submucosa
      after ulceration, starting as soon as 3 days after the insult and continuing for
      several weeks. The devised method of combined in-situ hybridization and
      immunohistochemistry can be used with standard paraffin-embedded tissues, yields
      results within 2 days, and avoids radioisotopes.

PMID- 9027302
TI  - Transthyretin distribution in the developing choroid plexus of the South American
      opossum (Monodelphis domestica).
AB  - The distributions of transthyretin and albumin in the choroid plexus during brain
      development have been compared. The South American opossum was chosen because the
      young are born around the time of choroid plexus formation. Previous work showed
      that in the adult opossum, transthyretin is expressed in the choroid plexus
      cells. However, systematic studies of transthyretin in the choroid plexus during
      development have not been carried out before. Transthyretin was present in 90-95%
      of the choroidal cells form birth to adulthood. In most cells, transthyretin
      immunoreactivity was concentrated in the apical region of the cytoplasm. Double
      labelling of choroid plexus sections with antibodies to albumin and transthyretin
      showed that 1-2% of cells were positive for both proteins. These findings suggest
      that from the very earliest stage of choroid plexus formation most epithelial
      cells both synthesize and contain transthyretin, and a few of these transthyretin
      synthesizing cells also contain albumin that is probably being transferred form
      blood to the cerebrospinal fluid.

PMID- 9027304
TI  - Nanofabrication of Small Copper Clusters on Gold(111) Electrodes by a Scanning
      Tunneling Microscope
AB  - The use of scanning tunneling microscopy in an electrochemical environment as a
      tool for the nanoscale modification of gold electrodes was demonstrated. Small
      copper clusters, typically two to four atomic layers in height, were precisely
      positioned on a gold(111) electrode by a process in which copper was first
      deposited onto the tip of the scanning tunneling microscope, which then acted as
      a reservoir from which copper could be transferred to the surface during an
      appropriate approach of the tip to the surface. Tip approach and position were
      controlled externally by a microprocessor unit, allowing the fabrication of
      various patterns, cluster arrays, and "conducting wires" in a very flexible and
      convenient manner.

PMID- 9027305
TI  - Five-Coordinate Hydrogen: Neutron Diffraction Analysis of the Hydrido Cluster
      Complex
AB  - Pentacoordinate hydrogen atoms were identified by single-crystal neutron
      diffraction analysis of [N(CH3)4]3[H2Rh13(CO)24]. The hydrogen atoms are located
      in square pyramidal cavities of the Rh13 cluster, in positions almost coplanar
      with the Rh4 faces on the surface of the cluster. They are slightly displaced
      inward, toward the central rhodium atom of the cluster, with average H
      Rh(central) and H-Rh(surface) distances of 1.84(2) and 1.97(2) angstroms,
      respectively. This result shows that hydrogen, which normally forms only one
      bond, can be attached to five other atoms simultaneously in a large metal
      cluster.

PMID- 9027306
TI  - Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman
      Scattering
AB  - Optical detection and spectroscopy of single molecules and single nanoparticles
      have been achieved at room temperature with the use of surface-enhanced Raman
      scattering. Individual silver colloidal nanoparticles were screened from a large
      heterogeneous population for special size-dependent properties and were then used
      to amplify the spectroscopic signatures of adsorbed molecules. For single
      rhodamine 6G molecules adsorbed on the selected nanoparticles, the intrinsic
      Raman enhancement factors were on the order of 10(14) to 10(15), much larger than
      the ensemble-averaged values derived from conventional measurements. This
      enormous enhancement leads to vibrational Raman signals that are more intense and
      more stable than single-molecule fluorescence.

PMID- 9027307
TI  - Direct measurement of single-molecule diffusion and photodecomposition in free
      solution.
AB  - Continuous monitoring of submillisecond free-solution dynamics of individual
      rhodamine-6G molecules and 30-base single-stranded DNA tagged with rhodamine was
      achieved. Fluorescence images were recorded from the same set of isolated
      molecules excited either through the evanescent field at the quartz-liquid
      interface or as a thin layer of solution defined by micron-sized wires, giving
      diffraction-limited resolution of inter-connected attoliter volume elements. The
      single-molecule diffusion coefficients were smaller and the unimolecular
      photodecomposition lifetimes were longer for the dye-DNA covalent complex as
      compared with those of the dye molecule itself. Unlike bulk studies, stochastic
      behavior was found for individual molecules of each type, and smaller diffusion
      coefficients were observed.

PMID- 9027308
TI  - Mass survival of birds across the Cretaceous-Tertiary boundary: molecular
      evidence.
AB  - The extent of terrestrial vertebrate extinctions at the end of the Cretaceous is
      poorly understood, and estimates have ranged from a mass extinction to limited
      extinctions of specific groups. Molecular and paleontological data demonstrate
      that modern bird orders started diverging in the Early Cretaceous; at least 22
      avian lineages of modern birds cross the Cretaceous-Tertiary boundary. Data for
      several other terrestrial vertebrate groups indicate a similar pattern of
      survival and, taken together, favor incremental changes during a Cretaceous
      diversification of birds and mammals rather than an explosive radiation in the
      Early Tertiary.

PMID- 9027309
TI  - Muscular force in running turkeys: the economy of minimizing work.
AB  - During running, muscles and tendons must absorb and release mechanical work to
      maintain the cyclic movements of the body and limbs, while also providing enough
      force to support the weight of the body. Direct measurements of force and fiber
      length in the lateral gastrocnemius muscle of running turkeys revealed that the
      stretch and recoil of tendon and muscle springs supply mechanical work while
      active muscle fibers produce high forces. During level running, the active muscle
      shortens little and performs little work but provides the force necessary to
      support body weight economically. Running economy is improved by muscles that act
      as active struts rather than working machines.

PMID- 9027310
TI  - Mass Spawning by Green Algae on Coral Reefs
AB  - Predawn episodes of mass spawning by green algae (up to nine species in five
      genera on a single morning) intermittently cloud Caribbean waters. Species- and
      sex-specific bouts of anisogamous gamete release occurred synchronously and
      predictably on a given morning, with closely related species spawning at
      different times. Algal sexual reproduction was seasonal, but, unlike the mass
      spawning behavior of other sessile marine organisms, showed no lunar or tidal
      cycling. The discovery of mass-spawning behavior by these algae has important
      implications for future studies of the reproductive ecology and speciation of a
      vital, yet poorly understood, component of the coral reef community.

PMID- 9027311
TI  - Calmodulin regulation of calcium stores in phototransduction of Drosophila.
AB  - Phototransduction in Drosophila occurs through the ubiquitous phosphoinositide
      mediated signal transduction system. Major unresolved questions in this pathway
      are the identity and role of the internal calcium stores in light excitation and
      the mechanism underlying regulation of Ca2+ release from internal stores.
      Treatment of Drosophila photoreceptors with ryanodine and caffeine disrupted the
      current induced by light, whereas subsequent application of calcium-calmodulin
      (Ca-CaM) rescued the inactivated photoresponse. In calcium-deprived wild-type
      Drosophila and in calmodulin-deficient transgenic flies, the current induced by
      light was disrupted by a specific inhibitor of Ca-CaM. Furthermore, inhibition of
      Ca-CaM revealed light-induced release of calcium from intracellular stores. It
      appears that functional ryanodine-sensitive stores are essential for the
      photoresponse. Moreover, calcium release from these stores appears to be a
      component of Drosophila phototransduction, and Ca-CaM regulates this process.

PMID- 9027312
TI  - Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death.
AB  - Previous genetic studies of the nematode Caenorhabditis elegans identified three
      important components of the cell death machinery. CED-3 and CED-4 function to
      kill cells, whereas CED-9 protects cells from death. Here CED-9 and its mammalian
      homolog Bcl-xL (a member of the Bcl-2 family of cell death regulators) were both
      found to interact with and inhibit the function of CED-4. In addition, analysis
      revealed that CED-4 can simultaneously interact with CED-3 and its mammalian
      counterparts interleukin-1beta-converting enzyme (ICE) and FLICE. Thus, CED-4
      plays a central role in the cell death pathway, biochemically linking CED-9 and
      the Bcl-2 family to CED-3 and the ICE family of pro-apoptotic cysteine proteases.

PMID- 9027313
TI  - Interaction and regulation of subcellular localization of CED-4 by CED-9.
AB  - The Caenorhabditis elegans survival gene ced-9 regulates ced-4 activity and
      inhibits cell death, but the mechanism by which this occurs is unknown. Through a
      genetic screen for CED-4-binding proteins, CED-9 was identified as an interacting
      partner of CED-4. CED-9, but not loss-of-function mutants, associated
      specifically with CED-4 in yeast or mammalian cells. The CED-9 protein localized
      primarily to intracellular membranes and the perinuclear region, whereas CED-4
      was distributed in the cytosol. Expression of CED-9, but not a mutant lacking the
      carboxy-terminal hydrophobic domain, targeted CED-4 from the cytosol to
      intracellular membranes in mammalian cells. Thus, the actions of CED-4 and CED-9
      are directly linked, which could provide the basis for the regulation of
      programmed cell death in C. elegans.

PMID- 9027314
TI  - Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria
      blocked.
AB  - Bcl-2 is an integral membrane protein located mainly on the outer membrane of
      mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in
      response to a variety of stimuli. Cytosolic cytochrome c is necessary for the
      initiation of the apoptotic program, suggesting a possible connection between Bcl
      2 and cytochrome c, which is normally located in the mitochondrial intermembrane
      space. Cells undergoing apoptosis were found to have an elevation of cytochrome c
      in the cytosol and a corresponding decrease in the mitochondria. Overexpression
      of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the
      initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of
      apoptosis is to block cytochrome c release from mitochondria.

PMID- 9027315
TI  - The release of cytochrome c from mitochondria: a primary site for Bcl-2
      regulation of apoptosis.
AB  - In a cell-free apoptosis system, mitochondria spontaneously released cytochrome
      c, which activated DEVD-specific caspases, leading to fodrin cleavage and
      apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the
      release of cytochrome c and thus caspase activation. During apoptosis in intact
      cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a
      caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the
      inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in
      mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c
      translocation, thereby blocking caspase activation and the apoptotic process.

PMID- 9027316
TI  - Role for the amino-terminal region of human TBP in U6 snRNA transcription.
AB  - Basal transcription from the human RNA polymerase III U6 promoter depends on a
      TATA box that recruits the TATA box-binding protein (TBP) and a proximal sequence
      element that recruits the small nuclear RNA (snRNA)-activating protein complex
      (SNAPc). TBP consists of a conserved carboxyl-terminal domain that performs all
      known functions of the protein and a nonconserved amino-terminal region of
      unknown function. Here, the amino-terminal region is shown to down-regulate
      binding of TBP to the U6 TATA box, mediate cooperative binding with SNAPc to the
      U6 promoter, and enhance U6 transcription.

PMID- 9027318
TI  - Circadian rhythms and autoregulatory transcription loops--going round in circles?
AB  - Recent advances in the molecular analysis of biological timing have appeared to
      bring us closer to an answer to the 'big question', namely, 'What is the timing
      mechanism that enables an organism to measure the circadian (around 24 h)
      period?'. In this minireview, we consider the validity of the fashionable concept
      that autoregulatory feedback loops, centered on transcription, form the basis of
      the clock, and we offer a fresh view of recent progress as it relates to
      mammalian systems.

PMID- 9027317
TI  - Structural convergence in the active sites of a family of catalytic antibodies.
AB  - The x-ray structures of three esterase-like catalytic antibodies identified by
      screening for catalytic activity the entire hybridoma repertoire, elicited in
      response to a phosphonate transition state analog (TSA) hapten, were analyzed.
      The high resolution structures account for catalysis by transition state
      stabilization, and in all three antibodies a tyrosine residue participates in the
      oxyanion hole. Despite significant conformational differences in their combining
      sites, the three antibodies, which are the most efficient among those elicited,
      achieve catalysis in essentially the same mode, suggesting that evolution for
      binding to a single TSA followed by screening for catalysis lead to antibodies
      with structural convergence.

PMID- 9027319
TI  - Selenium deficiency and thyroid fibrosis. A key role for macrophages and
      transforming growth factor beta (TGF-beta).
AB  - Free radical damage and fibrosis caused by selenium deficiency are thought to be
      involved in the pathogenesis of myxoedematous cretinism. So far, no pathway
      explains the link between selenium deficiency and tissue fibrosis.
      Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids.
      Necrosis is much increased if the glands are also selenium-deficient, which then
      evolve to fibrosis. This rat model was reproduced to explore the role of selenium
      deficiency in defective tissue repair. At first, proliferation indexes of
      epithelial cells and fibroblasts were comparable between selenium-deficient and
      control groups. Then, in selenium-deficient thyroids the inflammatory reaction
      was more marked being mainly composed of macrophages. The proliferation index of
      the epithelial cells decreased, while that of the fibroblasts increased. These
      thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the
      macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the
      proliferation indexes, and blocked the evolution to fibrosis. In selenium
      deficiency, an active fibrotic process occurs in the thyroid, in which the
      inflammatory reaction and an excess of TGF-beta play a key role.

PMID- 9027320
TI  - Characteristics of tumor cell bioactivity in oncogenic osteomalacia.
AB  - Oncogenic osteomalacia is a condition where renal phosphate wasting occurs
      causing defective mineralisation, in the presence of a tumor. Cultures of cells
      were established from a hemangiopericytoma resected from a patient with oncogenic
      osteomalacia. Conditioned media from the cells inhibited phosphate uptake in
      opossum kidney cells and stimulated of cAMP in rat osteosarcoma cells, a standard
      parathyroid hormone (PTH)-like assay. This cAMP stimulation was suppressed by the
      PTH analogue, 3-34 bPTH and also by heat and trypsin treatment of the media.
      Tests of conditioned media for PTH and parathyroid hormone related protein
      (PTHrP) immunoreactivity were negative, however, and no hybridisation to probes
      for PTH, PTHrP or human stanniocalcin was detected in tumor cell RNA on Northern
      blot. These data support the hypothesis that tumors responsible for oncogenic
      osteomalacia produce a humoral substance that reduces renal phosphate
      reabsorption and provide evidence that the factor may act via PTH/PTHrP
      receptors.

PMID- 9027321
TI  - Structure and expression of the mouse oxytocin receptor gene.
AB  - To determine the structure of the mouse oxytocin receptor (OTR) gene, we have
      screened a mouse genomic library and confirmed cDNA sequence with rapid
      amplification of cDNA ends. Southern blot using human OTR cDNA probes indicated
      that the mouse genome has a single copy of the gene. The predicted amino acid
      sequence is 91% identical to human OTR. The gene contains 4 exons and 3 introns.
      Exons 1 and 2 contain the 5' untranslated region, with exons 3 and 4 encoding the
      amino acids of the receptor. Intron 3 interrupts the coding at the same location,
      after transmembrane domain 6, as in OTR genes of other species. The promoter
      region lacks an apparent TATA box but contains multiple putative interleukin
      response elements and estrogen responsive elements. Expression of OTR gene in the
      uterus during pregnancy reached maximum at day 20 gestation. The information
      obtained from the mouse OTR gene facilitates further comparative and biochemical
      analysis for protein structure-function relationships and gene regulatory
      mechanisms.

PMID- 9027322
TI  - Interleukin-2 (IL-2) and IL-6 regulate c-fos protooncogene expression in human
      pituitary adenoma explants.
AB  - We have previously shown that interleukin-2 (IL-2) and IL-6, which are expressed
      in the anterior pituitary, affect anterior pituitary cell proliferation in normal
      rats and cell lines. Here we examined their effects on the c-fos expression by
      human anterior pituitary adenomas. Adenoma cells in culture do not express c-fos
      mRNA. In adenoma explants, however, c-fos expression was detected and was
      regulated by IL-2 or IL-6. In different tumors (ACTH-, PRL-, GH-secreting and non
      functioning adenomas), these interleukins had inhibitory or stimulatory effects
      but the kind of response does not seem to be associated to tumor type or size.
      Using blocking antibodies, we observed that intrinsic IL-2 and IL-6 regulate c
      fos expression in the same way. Our data suggest that IL-2 and IL-6 are not only
      involved in the regulation of pituitary adenoma function but may also, given the
      role of c-fos in cell proliferation, be implicated in the development of human
      pituitary adenomas.

PMID- 9027323
TI  - Functional characterization of five V2 vasopressin receptor gene mutations.
AB  - COS7 cells were transiently transfected with plasmids encoding mutant forms of
      the V2 vasopressin receptors corresponding to mutations [Y280C, L292P, R337stop,
      V277A, and G12E (the latter found in the same kindred with L292P)] recently
      identified in subjects with X-linked nephrogenic diabetes insipidus (NDI). cAMP
      response to dDAVP and AVP, saturation binding experiments with [3H]-AVP,
      immunofluorescence, and indirect ELISA studies were performed to characterize the
      functional consequences of these mutations. The Y280C, L292P, and R337stop mutant
      V2 receptors show substantially decreased cell surface expression and are
      functionally inactive. The V277A mutant receptor, though well expressed at the
      cell surface as seen by immunofluorescence and ELISA and having a dissociation
      constant with AVP similar to the wild type receptor, was functionally less active
      as seen by a substantially decreased receptor number (Bmax) and reduced cAMP
      stimulation by dDAVP. The G12E mutant was functionally the same as the wild type
      V2 receptor in both cAMP stimulation and binding. These results provide insight
      into residues critical for V2 receptor expression and function and also provide
      direct evidence that Y280C, L292P, R337stop and V277A mutations are the cause of
      X-linked NDI in affected subjects.

PMID- 9027324
TI  - Transcriptional regulation of the human chromogranin A gene by its 5' distal
      regulatory element: novel effects of orientation, structure, flanking sequences,
      and position on expression.
AB  - In previous studies of human chromogranin A (hCgA) gene expression, we had
      identified a 27 bp distal regulatory element (DRE) located between -576 and -550
      bp that interacts with a CRE-containing promoter to enhance gene transcription
      specifically in neuroendocrine (NE) cells. To characterize the DRE we have now
      mutated its various parts and assessed the effects on protein binding by
      electrophoretic mobility shift assays (EMSAs) and hCgA transcription within BEN
      cells. We found that the sequence TGACTAA, an AP-1 binding site that we refer to
      as DRE-AP-1, was necessary but not sufficient to produce the DRE's enhancer
      effect. Moreover, while AP-1 (Jun/Fos) bound this site, binding was not
      correlated with transcriptional effects. Protein binding by the DRE-AP-1 could be
      attenuated by mutations of its flanking sequences, and transcriptional
      enhancement by the DRE was dependent on its orientation and spatial relationship
      to the hCgA proximal promoter. Mutation of the DRE-AP-1 to a consensus AP-1 did
      not produce greater transcriptional activity, even though it increased binding of
      nuclear factors. Co-transfection with c-jun and/or c-fos expression plasmids
      showed that the DRE was unresponsive to the over-expressed AP-1 proteins. Co
      transfection with wild-type DRE oligonucleotides competitively inhibited DRE
      mediated transcription, while co-transfection with mutant DRE oligonucleotides
      had a lesser effect. Our studies indicate that transcriptional enhancement of
      hCgA by the DRE is dependent on a unique NE-specific DRE-binding factor, which we
      refer to as DBF, that specifically and directionally binds the DRE to assemble
      and synergize a functional transcription complex.

PMID- 9027325
TI  - Autocrine mechanism of epidermal growth factor in choriocarcinoma cell
      proliferation.
AB  - We examined four choriocarcinoma cell lines, NaUCC-1, NaUCC-3, NaUCC-4 and BeWo,
      for the presence of epidermal growth factor (EGF) by enzyme immunoassay and
      reverse transcription and polymerase chain reaction, and for EGF receptor (EGFR)
      by 125I-EGF binding assay. Specific EGF binding and EGF proteins were detected in
      these four choriocarcinoma cell lines. On the cell lines examined, NaUCC-4 had
      the greatest EGF binding capacity (18 x 10(5) sites/cell) and the highest amount
      of immunoreactive EGF (142 pg/ml). These results prompted us to assess the
      significance of EGF/EGFR autocrine mechanism in NaUCC-4 cells. Low doses of
      exogenous EGF stimulated 3H-thymidine incorporation, and monoclonal antibodies
      against EGF or EGFR dose-dependently inhibited 3H-thymidine incorporation. On the
      other hand, these antibodies did not significantly affect hCG production. These
      results suggested that EGF might function in an autocrine manner to stimulate
      proliferation rather than differentiation of NaUCC-4 choriocarcinoma cells.

PMID- 9027326
TI  - Interaction between estradiol and cAMP in the regulation of specific gene
      expression.
AB  - The mRNA levels of LIV-1 and pS2, two estrogen-responsive genes, are increased by
      the agents, cholera toxin (CT) plus 3-isobutyl-l-methylxanthine (IBMX), which
      cause an increase in cAMP in MCF-7 human breast cancer cells. The simultaneous
      addition of estradiol and CT/IBMX results in a synergistic induction of the two
      mRNAs. The changes in mRNA reflect changes in transcription of the two genes.
      Interestingly, the addition of CT/IBMX to estradiol not only causes a greater
      increase in transcription rate but the increase is longer-lasting that seen with
      the hormone alone. Stimulation of mRNA levels by CT/IBMX, but not by estradiol,
      was prevented by cycloheximide. Stimulation by both estradiol and by CT/IBMX was
      prevented by the antiestrogen, ICI 164387. Transcription of LIV-1 and pS2 genes
      is by both estradiol and cAMP, via separate mechanisms both requiring the
      estrogen receptor.

PMID- 9027327
TI  - Protein kinase C pathway potentiates androgen-mediated gene expression of the
      mouse vas deferens specific aldose reductase-like protein (MVDP).
AB  - Transcription of the mouse vas deferens protein (MVDP) gene, a member of the aldo
      keto reductase superfamily, is stimulated by androgens via the androgen
      responsive element (ARE) located in the proximal promoter (-111 to -97). We
      investigated interaction between androgens and the protein kinase C (PKC)
      signalling pathway. Transcriptional regulation was determined by analysis of
      chloramphenicol acetyltransferase (CAT). T47D cells were transiently transfected
      with 5' flanking MVDP DNA promoter sequences (-1804 to +41; -510 to +41 and -121
      to +41) fused to the reporter (CAT) gene. Androgen-induced transcriptional
      activity can be enhanced from 6 (1.8 and 0.5 kb MVDP-CAT constructs) to 18 fold
      (0.16 kb MVDP-CAT construct), in a time and dose-dependent manner, by the PKC
      activator 12-o-tetradecanoylphorbol-13 acetate (TPA). A mutation in the proximal
      ARE abolished both androgen and TPA-dependent gene enhancement. TPA influenced
      minimally MMTV promoter in T47D cells and MVDP promoter in CV1 cells suggesting
      that the effects of the PKC activator are probably promoter and cell-specific. In
      contrast, activation of protein kinase A (PKA) via addition of dibutyryl-cAMP (db
      cAMP) reduced androgen induction of the MVDP gene.

PMID- 9027328
TI  - Hormonal regulation of FHG22 mRNA in Syrian hamster harderian glands: role of
      estradiol.
AB  - The regulation of the FHG22 gene by sex steroids has been studied in Syrian
      hamster Harderian gland, an organ with sexual dimorphism in which the FHG22 mRNA
      is female-specific. Testosterone treatment of females caused irregular inhibitory
      effects on the FHG22 mRNA levels, whereas male castration originated transitory
      increases during less than 2 weeks. Treatment of 15 day-castrated males for 1 or
      2 days with beta-estradiol-3-benzoate caused a marked stimulation in the FHG22
      mRNA levels. The results found in vivo may be explained considering those found
      in female Harderian gland serum-free primary cell cultures. In the absence of
      hormones, the FHG22 mRNA levels decreased along the time and neither
      progesterone, testosterone, or 5 alpha-dihydrotestosterone affected the
      expression. However, estradiol stimulated the FHG22 mRNA expression in a time and
      dose-dependent manner: increasing effects were detected between 8-96 h of
      treatment and the EC50 was about 10(-9) M. The estradiol effect was reverted by
      the antiestrogen ICI 164,384 or by cycloheximide. We conclude that estradiol
      stimulates FHG22 mRNA expression in Harderian gland, although other agents may
      also control the expression in vivo.

PMID- 9027330
TI  - Autoregulation of androgen receptor in rat ventral prostate: involvement of c-fos
      as a negative regulator.
AB  - Recent work from our laboratory has focused on elucidating the mechanism of
      androgen regulation of the androgen receptor (AR). We have demonstrated that
      testosterone increases AR protein and binding within 1 h in the ventral prostate
      of adult rats castrated for 24 h. Cycloheximide administered with testosterone
      reduces AR and AR mRNA levels. AP-1/c-fos transcription factor has been shown to
      function as a negative in many systems. c-fos mRNA levels were decreased 1 h
      after testosterone treatment in the ventral prostate, whereas they were increased
      in cycloheximide alone or cycloheximide-testosterone treated groups as compared
      to vehicle control. c-fos protein was also increased in the testosterone
      cycloheximide treated group as compared to testosterone alone or cycloheximide
      alone groups at 1 h. By 3 h, the tissue recovers from the inhibitory effect of
      cycloheximide as evidenced by restoration of AR and an increase in AR mRNA
      levels. At this time c-fos protein levels were reduced after treatment with
      cycloheximide and testosterone and c-fos mRNA levels were comparable to the
      controls. These results suggest that elevation of c-fos expression is associated
      with a decrease in AR and mRNA and provide correlative data supporting negative
      repression by c-fos on androgen receptors levels. Between the age of 25-85 days,
      serum testosterone levels reached adult levels by the age of 55 days. Steady
      state AR mRNA levels increased significantly by the age of 85 days while c-fos
      mRNA levels remained at low baseline levels at all ages. Thus, in addition to the
      circulating levels of serum testosterone, other age related factors are also
      involved in the regulation of AR mRNA levels. Furthermore, androgens appear to
      maintain androgen receptor levels and androgen sensitivity by continuous
      suppression of the repressor, c-fos.

PMID- 9027329
TI  - ACTH and AII differentially stimulate steroid hormone orphan receptor mRNAs in
      adrenal cortical cells.
AB  - NGFI-B and Ad4BP are steroid hormone receptor-like transcription factor that may
      control steroidogenesis, growth and differentiation in the adrenal cortex. We
      have studied the induction of NGFI-B and Ad4BP and mRNAs by the peptide hormones,
      ACTH, AII, IGF, FGF, and by KCl depolarization in cultured bovine adrenocortical
      cells. The mRNAs for these two transcription factors were most effectively but
      differentially induced by ACTH and AII. mRNA for NGFI-B was typically
      undetectable in unstimulated cells, but rapidly (< 30 min) accumulated in
      response to ACTH and AII. Peak increases occurred within 2-3 h after which mRNA
      levels declined. At maximally effective concentrations, AII produced increases in
      NGFI-B mRNA 2.7-fold larger than those triggered by ACTH (n = 7). In contrast to
      NGFI-B, Ad4BP mRNA was readily detectable in unstimulated cells. ACTH and AII
      induced smaller, slower and more sustained increases in Ad4BP mRNA. Peak values
      were obtained in 6-8 h and Ad4BP mRNA remained elevated for at least 18 h. ACTH
      produced increases in Ad4BP that were 2.6-fold larger than those stimulated by
      AII (n = 8). Antagonists of major signaling pathways that couple ACTH and AII
      receptors to cortisol secretion, including T-type Ca2+ antagonist Ni2+ and
      penfluridol, the CaM kinase antagonist KN-62, the A-kinase antagonist H-89 and
      the non-selective kinase antagonist staurosporine, all failed to suppress
      increases in NGFI-B and Ad4BP mRNAs triggered by these two peptides. Each of
      these agents effectively inhibited cortisol production stimulated by the
      peptides. Further, arguing against their proposed role as transcription factors
      for steroidogenic enzymes, ACTH- and AII-stimulated increases in steroid orphan
      receptor mRNAs were not correlated with corresponding increases in cortisol
      production measured over 24 h. The results show that NGFI-B and Ad4BP mRNAs are
      differentially regulated by ACTH and AII. Only NGFI-B is rapidly and transiently
      increased with kinetics common to immediate early genes. The lack of correlation
      between peptide-stimulated increases in orphan receptor mRNAs and cortisol
      production in combination with the apparent divergence in the associated
      signaling pathways argue against a primary role for these transcription factors
      in ACTH- and AII-stimulated steroidogenesis. The dual function of these peptide
      hormones as mediators of development and corticosteroid synthesis could
      necessitate the presence of separate, parallel signaling pathways.

PMID- 9027331
TI  - Most lactotrophs from lactating rats are able to respond to both thyrotropin
      releasing hormone and dopamine.
AB  - Intracellular free calcium concentration ([Ca2+]i) was measured with video
      imaging in lactotrophs from lactating rats. The median resting [Ca2+]i was 24 nM
      (85 cells). The great majority of cells responded to thyrotropin-releasing
      hormone (TRH) with an increase in [Ca2+]i, (median peak [Ca2+]i after TRH = 298
      nM; n = 73). In 77% of these cells this [Ca2+]i increase was biphasic, with
      [Ca2+]i remaining high after the initial peak (median [Ca2+]i 90 s after TRH
      application = 104 nM; n = 56); the second phase depended on calcium influx. Most
      cells also responded to dopamine (DA), after TRH had been applied. DA reduced or
      abolished TRH-induced calcium influx and also reduced resting [Ca2+]i if this was
      above its initial value. A few lactotrophs responded to TRH only after DA
      application and withdrawal. We conclude that the population of lactotrophs in
      lactating rats is heterogeneous, but is not composed of two distinct sub-groups
      defined by their responsiveness to TRH or DA.

PMID- 9027332
TI  - Characterization of the insulin-like growth factor type 1 receptor messenger in
      two teleost species.
AB  - The insulin-like growth factor type 1 receptor (IGF-1R) is a tyrosine kinase
      which plays essential role in the regulation of growth and development. In this
      study, we have cloned cDNAs encoding the tyrosine kinase domain of the IGF-1R
      from two species of fish. The turbot and trout nucleotide sequences share 82%
      identity. Moreover, the deduced polypeptides are also highly conserved (> 90%
      identity) compared with the IGF-1R sequences described in other vertebrates,
      particularly within domains involved in the catalytic activity and in the
      transduction pathway. Northern blot analyses have revealed a unique 13-kb mRNA
      transcript. Using an RT-PCR approach, we have also shown that the polyadenylation
      status seems to vary according to the developmental stage in turbot:
      polyadenylated in oocytes and in the first larval stages, the mRNA becomes
      undetectable in the polyadenylated fraction in later stages or in adult somatic
      tissues. These results suggest that IGF-1R mRNA undergoes complex post
      transcriptional regulation.

PMID- 9027333
TI  - Modulatory action of epidermal growth factor on differentiated human granulosa
      lutein cells: cross-talk between ligand activated receptors for EGF and
      gonadotropin.
AB  - A number of local regulatory factors including polypeptide growth factors like
      epidermal growth factor (EGF) have been suggested to play an active role within
      the human ovary. In order to understand the physiology of EGFs action, it is
      essential to demonstrate and characterize the receptors for this growth factor on
      ovarian cells which was the aim of this study. We demonstrate using [125I]EGF
      that specific high affinity sites with Ka for this ligand reaching 2.2 x 10(-9) M
      for growing cultures of human granulosa-lutein cells and 0.13 x 10(-9) M for the
      membrane fraction prepared from these cells. Additionally we have identified a
      170 kD protein as the EGF receptor with the help of affinity cross linking and
      immunoblotting procedures. Furthermore, we observed that a pretreatment of
      granulosa lutein cells with EGF for a short duration (0-30 min) leads to a dose-
      and time dependent upregulation of the LH-receptor-coupled adenylate cyclase
      activity. A maximal effect (159 +/- 12% increase compared with untreated cells, P
      < 0.001, n = 4) was reached at 10-15 min with 10-20 ng/ml EGF. Specific
      inhibition of the receptor tyrosine kinase activity abolished the observed EGF
      induced sensitization of the cyclase activity. Differentiation of granulosa cells
      in vivo is a prerequisite for ovulation and later transformation into highly
      differentiated lutein cells, a process depending on the presence of ligands that
      elevate cAMP production. The observed modulation of the adenylate cyclase by EGF
      could be a regulatory component for the differentiated status of the granulosa
      cells during different phases of the cycle.

PMID- 9027334
TI  - hCG beta residues 94-96 alter LH activity without appearing to make key receptor
      contacts.
AB  - The ability of human chorionic gonadotropin (hCG) to distinguish lutropin (LHR)
      and follitropin (FSHR) receptors is controlled principally by beta-subunit
      residues 94-117. To learn how residues 94-96 (Arg-Arg-Ser) influence LHR binding,
      we studied the effects of replacing them on the LH and FSH activities of a
      bifunctional hCG analog in which residues 101-109 were derived from FSH. Analogs
      containing 1-3 arginines and no aspartates at residues 94-96 bound LHR with 25
      400% the potency of hCG. When residues 94-96 were neutral or contained 1-3
      aspartates, LHR binding was reduced 6-100 fold but remained at least ten-fold
      greater than the negative control analog containing residues 94-117 derived from
      FSH. Residues 94-96 had little influence on FSHR binding. These observations
      support a model [Moyle et al. (1995) J. Biol. Chem. 270:20,020] in which residues
      94-96 influence LHR binding specificity primarily through an effect on hormone
      conformation rather than by direct participation in essential high affinity
      receptor contacts.

PMID- 9027335
TI  - Function of the conserved Pit-1 gene distal enhancer in progenitor and
      differentiated pituitary cells.
AB  - Pit-1 is a homeodomain transcription factor that is required for the function and
      survival of the hormone-secreting somatotrope, lactotrope and thyrotrope cells of
      the anterior pituitary gland. Within the upstream region of the mouse Pit-1 gene
      at around -10 kb, a complex transcriptional enhancer confers autoregulation and
      response to hormones and morphogens upon the gene. We demonstrate that this
      enhancer is conserved in both sequence and function and that related sequences
      are present in other rodents. Enhancer sequences from mouse, rat and hamster Pit
      1 genes activated transcription from Pit-1 promoter reporter genes in a pituitary
      progenitor cell line, in somatolactotrope cells and conferred pituitary cell
      specific activation on heterologous promoters. Elements allowing regulation by
      vitamin D3, pituitary-specific factors and Pit-1-dependent response to retinoic
      acid are well conserved. Studies comparing distal enhancer activity with that of
      a second proposed enhancer sequence at -3 to -5 kb in the rat Pit-1 gene revealed
      that the distal enhancer has markedly higher activity than the -3 to -5 kb region
      in both progenitor and differentiated pituitary cell lines. The functional
      conservation of the distal enhancer element suggests that it is crucial to the
      maintenance and cell-specific regulation of the Pit-1 gene.

PMID- 9027337
TI  - Molecular cloning and characterization of mouse stanniocalcin cDNA.
AB  - In bony fish, stanniocalcin is a glycoprotein hormone thought to be an important
      regulator of calcium uptake from the aquatic environment. Although stanniocalcin
      was previously thought to be unique to fish, recent evidence has indicated the
      existence of a human homologue. To facilitate studies of the function of
      stanniocalcin in mammals, we have now isolated the mouse stanniocalcin cDNA. This
      cDNA encodes a predicted protein of the same length as its human counterpart and
      with a high level of similarity (238/247) amino acids are identical, and five
      represent conservative changes). As in human, the mRNA is expressed in many mouse
      tissues, suggesting that mammalian stanniocalcin has a paracrine rather than
      endocrine role.

PMID- 9027336
TI  - Transcriptional and post-transcriptional regulation of rainbow trout estrogen
      receptor and vitellogenin gene expression.
AB  - Estrogen receptor (ER) and vitellogenin (Vg) gene expression are strongly up
      regulated by estrogens in rainbow trout liver. In this paper, we have used
      primary cultured hepatocytes to examine the mechanisms implicated in estrogen
      regulation of ER and Vg gene expression. Treatment of hepatocytes with 1 microM
      estradiol (E2) led to a rapid increase in ER and mRNA level (15 fold) followed by
      Vg and mRNA induction. Transcription rate and mRNA half-life determination
      carried out in the presence or absence of E2, demonstrated that E2 increases both
      the ER and Vg gene transcriptional activity and mRNA stability (ca. 3 fold). The
      effect of E2 was inhibited by an excess of antiestrogen, showing that E2
      stimulation of ER and mRNA level is mediated by the estrogen receptor. Our data
      show that ER and Vg genes have different hormonal sensitivity. In fact, the Vg
      gene required a higher concentration of E2 to be stimulated compared to the ER
      gene. Examination of the mechanisms involved in post-transcriptional regulation
      of ER mRNA showed that the setting up and maintenance of this regulation process
      implies that estrogen receptor and the general translational activity within the
      cells, suggesting that ER mRNA depends on the synthesis of an estrogen-dependent
      protein. However, the cis and trans elements involved in E2-stabilization process
      remain to be identified.

PMID- 9027338
TI  - Gonadotropins and their receptors: structure, function and molecular forms.
      Conference proceedings. Paris, France, May 9-10, 1996.

PMID- 9027340
TI  - Three-dimensional structures of gonadotropins.
AB  - Most secreted proteins are modified post-translationally with the addition of
      carbohydrate. It has been difficult to use crystallography to solve the
      structures of these proteins due to the inherent heterogeneity of the
      carbohydrate. The structure of the chemically deglycosylated form (hydrogen
      fluoride treated) of human chorionic gonadotropin (hCG) has been solved through
      crystallographic techniques. Unfortunately this form of hCG is not biologically
      active, and exhibits immunochemical differences from native hormone. In addition,
      subunit interactions appear altered after chemical deglycosylation as indicated
      by the increased thermal stability of the HF-treated hormone. The Asn 52 glycan
      on the alpha-subunit of hCG has been identified as being required for biological
      activity, it is, therefore, of physiological importance to determine the
      structure of the hormone with its carbohydrate intact. Also, it has not been
      possible to obtain crystals of the individual glycosylated subunits of hCG.
      Therefore an alternative method to solve the structure of the biologically active
      form of the hormone in solution as well as its separated subunits is necessary.
      Structural information utilizing NMR techniques can be obtained from native hCG
      subunits in solution if they can be uniformly labeled with 13C and 15N isotopes.
      We have developed a universal nonradioactive isotope, labeling medium enriched in
      13C and 15N which can be used to express uniformly labeled hCG from Chinese
      hamster ovary cells suitable for solving the structure of the individual subunits
      and ultimately that of the native, biologically active hormone. The isotopically
      labeled recombinant hCG and its purified subunits are essentially identical to
      urinary hCG on comparison by biochemical, immunochemical, biological activity and
      the ability of the isolated subunits to recombine to form a biologically active
      dimer. Mass spectrometric analysis and preliminary structural NMR data indicate
      that the labeling is uniform and there is greater than 90% incorporation,
      sufficient for complete structural determination studies. This labeled growth
      medium represents a technological advance which will enable the rapid solution of
      the structures of the other glycoprotein hormones, as well as other glycoproteins
      which have proven unsuitable for crystallographic study.

PMID- 9027339
TI  - Structural features of mammalian gonadotropins.
AB  - There are two species for which both pituitary and placental gonadotropins are
      readily available, humans and horses. The human gonadotropins are better
      characterized than equine gonadotropins. Nevertheless, the latter are very
      interesting because they provide exceptions to some of the general structure
      function principles derived from studies on human and other mammalian
      gonadotropins. For example, separate genes encode the hLH beta and hCG beta
      subunits while a single gene encodes eLH beta and eCG beta. Thus, eCG and eLH
      differ only in their oligosaccharide moieties and eLH is the only LH that
      possesses the O-glycosylated C-terminal extension previously believed to be
      restricted to chorionic gonadotropins. Truncation experiments involving eLH beta
      and hCG beta have suggested the C-terminal extension has no effect on receptor
      binding. However, the largest of three eCG forms which differ only in the extent
      of O-glycosylation possessed reduced affinity for LH and FSH receptors. This
      result suggested that effects of O-glycosylation need to be considered when
      examining the glycosylation differences between eLH and eCG responsible for the
      10-fold lower eCG receptor binding affinity compared with that of eLH.
      Contribution of alpha Asn56 N-linked oligosaccharides to the different biological
      activities of eLH and eCG has been evaluated following selective removal using
      peptide-N-glycanase digestion of native equine alpha-subunit preparations.
      Hormones-specific patterns of glycosylation were observed on alpha Asn56 of eLH,
      eFSH, and eCG. Removal of alpha Asn56 oligosaccharides increased the rate of
      subunit association, the extent of association, and receptor binding activity.
      Some unassociated alpha-subunit oligosaccharides were identified which may
      interfere with subunit association because they were more abundant in
      unassociated subunit oligosaccharide maps than in a total oligosaccharide map.
      This was most striking in the case of eCG alpha in which two minor peaks became
      the major oligosaccharide peaks detectable in the unassociated eCG alpha fraction
      following association with eLH beta and eFSH beta. The biological activities
      exhibited by hybrid hormones, eLH alpha reassociated with oLH beta and pLH beta,
      found to be greater than those of oLH and pLH provided an interesting exception
      to the general rule that the beta-subunit determines the potency of the
      heterodimer. LH receptor binding activities of eLH beta-chimeric ovine/equine
      alpha-subunits suggested that the equine alpha-subunit N-terminal domain may be
      responsible for this effect. Equine FSH has higher FSH receptor binding activity
      than human, ovine, and porcine FSH preparations. This probably results from two
      factors. First, the presence of the equine alpha-subunit promotes receptor
      binding as noted above. Second, the overall -2 charge of the eFSH beta
      determinant loop, which is less negative that the -3 observed in other species,
      results from the presence of an Asn residue at position 88 instead of Asp. This
      apparently facilitates binding to the FSH receptor.

PMID- 9027341
TI  - Immunochemical mapping of gonadotropins.
AB  - As a glycoprotein hormone, human chorionic gonadotropic (hCG) is not a single
      molecular entity but this term rather comprises an array of molecular variants
      such as hCG, hCG beta, hCGn, hCG beta n, hCG beta cf, -CTPhCG, hCG beta CTP,
      deglyhCG, asialohCG, hCGav and the closely related molecules hLH, hLH beta and
      hLH beta ef. The advent of monoclonal antibodies (MCA), the availability of
      ultrasensitive detection systems and the recent determination of the crystal
      structure of hCG, made it possible to design special purpose diagnostic and
      clinical research immunoassays for hCG-like molecules. For more than a decade we
      and others have tried to refine epitope maps for hCG and related molecules by
      means of a large panel of MCA, naturally occurring metabolic variants of hCG
      (hCGn, hCG beta, hCG alpha, hCG beta cf, hCG beta CTP), homologous hormones and
      subunits of various species (e.g. hLH, hLH beta, hFSH, hTSH, oLH, rLH beta),
      chemically modified molecules (deglyhCG, asialohCG, tryptic and chymotryptic hCG
      beta and hCG alpha fragments) and synthetic peptides (octapeptides and longer).
      It appeared that all epitopes on molecular hCG-variants recognized by our MCA are
      determined by the protein backbone. Except for the two major epitopes on hCG beta
      CTP and parts of two antigenic domains on hCG alpha, epitopes on hCG-derived
      molecules are determined by the tertiary and quarternary structure. Operationally
      useful descriptive epitope maps were designed including information on assay
      suitability of antigenic determinants. On this basis we established
      ultrasensitive time-resolved fluoroimmuno-assays for hCG, hCG and hCGn, hCG beta
      and hCG beta n and hCG beta cf, hCG alpha and additional assays recognizing
      different spectra of hCG-variants. Such assay have been applied by us and others
      to the detection of pregnancy, early pregnancy loss, choriocarcinoma, testicular
      cancer, other cancers and prenatal diagnosis. However, as the molecular structure
      of many epitopes utilized in immunoassays of different laboratories was not
      resolved, comparability of results was not satisfactory. Consequently, attempts
      were made to compare schematic epitope maps from different research institutions.
      The situation has been much improved by solving the three-dimensional (3D)
      structure of hCG. It has been shown that hCG is a member of the structural
      superfamily of cystine knot growth factors like NGF, PDGF-B and TGF-beta. Each of
      its subunits is stabilized in its topology by three disulfide bonds forming a
      cystine knot. Moreover, it turned out that the disulfide bridges in their
      majority have previously been wrongly assigned. Computer molecular modeling of
      crystallographic coordinates of hCG and subsequent selective combined--PCR-based
      and immunological--mutational analyses of hCG beta expressed via the
      transmembrane region of a MHC molecule made it possible to more precisely
      localize epitopes on hCG-derived molecules. Although the entire surface of hCG
      has to be regarded as potentially immunogenic there seems to be hot spots where
      epitopes are clustered in antigenic domains. These are located on the first and
      third loops protuding from the cystine knots of both subunits and are possibly
      centered around the knot itself. Ultimate answers on epitope localizations will
      be given by the crystal structure determination of hCG complexed with different
      Fabs.

PMID- 9027342
TI  - Human follitropin heterodimerization and receptor binding structural motifs:
      identification and analysis by a combination of synthetic peptide and mutagenesis
      approaches.
AB  - The family of human glycoprotein hormones, including follitropin (FSH), are
      heterodimeric proteins, each composed of single alpha- and beta-subunits that are
      tightly associated but non-covalently linked. To study structure and function
      relationships of FSH, synthetic peptides were used to inhibit subunit
      association, to map epitopes of FSH antibodies and as antigens to generate site
      specific antipeptide antibodies which could be used for topographic analysis.
      Interpretation of such results are generally more straightforward than when
      peptides are used with radioreceptor assays or in cell cultures which are complex
      systems. The data we collected using the synthetic peptide approach suggested
      that FSH residues homologous to human chorionic gonadotropin (hCG) loops L3 beta
      and L2 alpha are involved in subunit contact. FSH residues homologous to hCG
      loops L2 beta and L3 alpha seemed involved in receptor binding. Loop L2 beta also
      seemed involved in subunit contact. Those data provided a rationale for extensive
      mutagenesis of the four regions of hFSH. Mutagenesis data provided additional
      information and higher resolution of function when combined with the three
      dimensional structure of hCG. In the aggregate, this information has provided a
      reasonable model of the receptor binding site of hFSH. Our current model of the
      FSH receptor site is that of a discontinuous functional epitope including L3
      beta, L2 alpha and L3 alpha. The juxtaposition of residues beta D93, alpha K5 1,
      alpha Y88 and of alpha Y89 in the 'binding-facet' of hFSH suggest the feasibility
      of designing a synthetic peptide mimetic of FSH. Additional residues of the alpha
      subunit are involved, along this facet of the molecule. The data collected
      studying hFSH therefore demonstrates that the alpha-subunit features prominently
      in the mechanism of FSH binding to and stabilizing the interaction with its
      receptor. In contrast, the beta-subunit determinant loop serves as discriminator
      in addition to stabilizing the binding interaction whereas mutagenesis data
      indicates that L2 beta does neither. Instead, L2 beta appears to stabilize FSH
      conformation, possibly, the alpha-subunit, required for competent binding. In
      this regard, synthetic peptides provided data which were a useful guide to plan
      mutagenesis studies and which contributed to the process of understanding the
      structure and function of the gonadotropins.

PMID- 9027343
TI  - hCG-receptor binding and transmembrane signaling.
AB  - The technique of site-directed mutagenesis has proven to be quite powerful in
      elucidating contact sites involved in the interaction of the heterodimeric
      glycoprotein hormones and their respective seven transmembrane (TM) G protein
      coupled receptors. Our laboratory has focused on identification of the minimum
      core sequences of the alpha and beta subunits required for bioactivity, the
      minimum length of a conjoined (yoked) single-chain hCG, the amino acid residues
      on hCG and the LH/CG-receptor (LH/CG-R) responsible for high-affinity binding,
      and the regions of the receptor that are involved in TM signaling. A number of
      amino acid residues have been mapped on the alpha and beta subunits of hCG that
      appear important in receptor binding. When projected onto the crystal structure
      of HF-treated hCG, these residues, by and large, cluster on one side of the
      molecule and cover a sizeable surface area, indicating that the hormone-receptor
      binding interface is rather extensive. Based on mutagenesis studies of several
      conserved ionizable amino acid residues in the extracellular domain (ECD) of
      LH/CG-R and a model that we, in collaboration with Drs Lapthorn and Isaacs, have
      developed for this region based on the crystal structure of porcine ribonuclease
      inhibitor, a charged region that appears to play an important role in hormone
      receptor recognition has been identified. We have also delineated several regions
      of LH/CG-R that do not appear to participate in hCG binding but are involved in
      hCG-mediated signaling. These regions are located in the ECD and extracellular
      loop III just prior to entry into the membrane via TM helices I and VII,
      respectively, and in TM helices VI and VII. Similarly, a homologous region in the
      ECD of the FSH receptor, located with ten residues of TM helix I, is important in
      signaling but not hormone binding. These results suggest that ligand binding and
      ligand-mediated receptor activation are quasi-distinct, albeit sequential
      phenomena. Collectively, our mutagenesis and modeling studies, coupled with
      results from other laboratories, argue for a ligand-induced conformational change
      of the receptor that may involve a relative reorientation of the TM helices.

PMID- 9027344
TI  - Advances in the molecular understanding of gonadotropins-receptors interactions.
AB  - The extracellular domain (ECD) of gonadotropin receptors belong to the leucine
      rich repeat (LRR) protein superfamily and their transmembrane domain (TMD) is
      characteristic of the seven alpha-helices G-protein-coupled receptors (GPCR). The
      availability of the X-ray structures of porcine ribonuclease inhibitor (RI), a
      LRR protein, and bacteriorhodopsin (bR) allows the construction of 3D models of
      the ECD and the TMD of gonadotropin receptors, respectively. The predicted models
      are to a large extent consistent with currently available biochemical and
      mutational data. The models provide a reliable basis for understanding how the
      hormone binds and activates its receptor. The ECD, in particular the LRR region,
      serves as a baseball glove which efficiently catches the large hormone and
      optimally orient the appropriate parts of it for interaction with the seven
      transmembrane-helix domain of the receptor. This in turn is expected to lead to a
      conformational change to be sensed by the appropriate G-protein complex leading
      to the stimulation of cAMP synthesis and steroids production.

PMID- 9027345
TI  - Expression of biologically active fusion genes encoding the common alpha subunit
      and either the CG beta or FSH beta subunits: role of a linker sequence.
AB  - The gonadotropin/thyrotropin hormone family is characterized by a heterodimeric
      structure composed of a common alpha subunit non-covalently linked to a hormone
      specific beta subunit. The conformation of the heterodimer is essential for
      controlling secretion, hormone-specific post-translational modifications and
      signal transduction. Structure-function studies of FSH and the other glycoprotein
      hormones are often hampered by mutagenesis induced defects in subunit
      combination. Thus, the ability to overcome the limitation of subunit assembly
      would expand the range of structure activity relationships that can be performed
      on these hormones. Here we converted the FSH heterodimer to a single chain by
      genetically fusing the carboxyl end of the FSH beta subunit to the amino end of
      the alpha subunit in the presence or absence of a natural linker sequence. In the
      absence of the CTP linker, the secretion rate was decreased over three fold. (The
      CTP sequence is the last 28 amino acids of the CG beta sequence and contains four
      serine-linked oligosaccharides). Unexpectedly however receptor binding/signal
      transduction was unaffected by absence of the linker. Molecular modelling of the
      tethers lacking the linker sequence show that the alignment of the alpha/beta
      domains in the single chain differ substantially from that seen in the
      heterodimer. These data show that the single chain FSH was secreted efficiently
      and is biologically active and that the conformation determinants required for
      secretion and biologic activity are not the same.

PMID- 9027346
TI  - Mapping of HCG-receptor complexes.
AB  - Molecular forms of the porcine LH/CG receptor (pLHR) and complexes between hCG
      and either the full-length pLHR or its extracellular domain (ectodomain) have
      been produced in various recombinant systems. In COS cells and in the baculovirus
      insect cells system, the co-expression of the ecto- and endo-domains
      reconstituted a functional receptor where the association of the two domains
      seems to depend upon the presence of disulfide bridges. According to previous
      observations [39], synthetic peptides mimicking three regions of the ectodomain
      (21-38, 100-115, 250-272) were found to inhibit hormone binding and stimulation
      of cAMP production. Antisera raised against these peptides contained anti-peptide
      antibodies (Ab) able to interfere with hormone signalling. Moreover, the results
      of peptide mapping indicated that some peptides stretches may be more involved in
      signalling rather than in binding. Immunochemical mapping based on monoclonal
      antibodies (mAbs) was used to probe the hCG-ectodomain complex. It appeared that
      mAbs directed to epitopes present on the 'beta-tip' of hCG (assembled from the
      beta subunit loops 3 and 1, and previously designated site IIIb) and on the
      'alpha-tip' (alpha subunit loops 1 and 3, site IIIa) bound to hCG-receptor
      complexes, whereas a conformational epitope (defined by the alpha-beta interface
      between beta seat belt C-terminus and alpha loop 2, site II) was masked.
      Interestingly, we and others previously reported that, in the hCG-full length
      receptor complex, site IIIa was shielded to mAb binding. A peptide mimicking the
      second extracellular loop (EL2) of the receptor endodomain was found to prevent
      the binding of a mAb directed to site IIIa, suggesting that this region of the
      endodomain may be interacting with the 'alpha-tip'. In the full-length, membrane
      anchored pLHR, the EL2 peptide inhibited hCG-induced cAMP production, but not
      binding. The possibility of inhibiting stimulation without inhibition of binding
      gives support to the 'negative specificity' hypothesis [6]. Thus, the ectodomain
      of the glycoprotein hormone receptors might be considered as a screening device
      preventing access of any glycoprotein hormone to the signalling peptide keys of
      the endodomain, which otherwise would be sensitive to any alpha subunit
      stimulation. Finally, antibody binding to site IIIa on the hCG-ectodomain complex
      was also hindered by an anti-peptide mAb directed against a peptide encoded by
      the eighth exon (pE x 8) of the LHR. This suggests that pEx8 is vicinal to the
      alpha-tip of hCG and to EL2 in the hCG-full length receptor complex. Altogether,
      these observations help to build up a topological model of the hCG-receptor
      complex.

PMID- 9027347
TI  - Molecular mechanism of LH/CG receptor activation.
AB  - It is known that the N-terminal half of the LH/CG receptor is responsible for
      high hCG binding whereas the C-terminal half is capable of receptor activation.
      Our results suggest that initial hCG binding at the high affinity site in the N
      half receptor induces conformational adjustments. This leads to low affinity
      secondary contacts of the complex of hCG/the N-half receptor with the C-half
      receptor. This low affinity secondary contact is responsible for activating the
      receptor. This is based on the following observations. The C-terminal tail of hCG
      alpha is known to be involved in activation of the LH/CG receptor. In addition to
      hCG, we examined the C-terminal three residues (His90-Lys91-Ser92) of the common
      alpha subunit of FSH and TSH. The results show their differential roles in the
      three hormones. Ser92 is important for binding and cAMP induction of TSH but not
      for hCG and FSH. Lys91 is important for binding and cAMP induction of hCG, and
      cAMP induction but not binding of FSH. It is not important for binding or cAMP
      induction of TSH. His90 is important for all three hormones. When all three
      residues were truncated, FSH and TSH lose their affinity for binding and cAMP
      induction, whereas hCG is still capable of binding but not cAMP induction.
      Therefore, the three amino acids contribute differently in receptor binding and
      cAMP induction of hCG, FSH and TSH. Our data also indicate that the evolution of
      the alpha subunit has been constrained in order not to impair any of the
      hormones. This suggests that each hormone can be independently engineered to
      improve the potency. To chemically identify the contact site of the alpha C-tail
      of hCG in the LH/CG receptor, a decamer peptide corresponding to the alpha
      subunit sequence from His83 to Ser92 (peptide alpha 81-92) was derivatized with
      UV sensitive reagent, ABG and radio-iodinated. The resulting ABG-125I-peptide
      alpha 83-92 was capable of binding and activating the LH/CG receptor.
      Furthermore, it specifically photoaffinity-labeled the LH/CG receptor. In
      addition, the amino group of alpha Lys91 of peptide alpha 83-92 is crosslinked to
      a carboxyl group of the receptor, an indication of close association. Reciprocal
      mutagenesis of alpha Lys91 and Asp397 in exoloop 1 of the LH/CG receptor suggests
      the complementary of this pair in receptor activation but not the high affinity
      interaction of hCG and the receptor. In addition, Lys583 of exoloop 3 is also
      crucial for receptor activation. To test the conformational adjustment, ABG was
      attached to hCG alpha and reassociated with untreated beta to produce ABG-125I
      alpha/beta. The extent of inter-subunit crosslinking of ABG-125I-alpha/beta bound
      to the receptor was two to three fold less than unbound ABG-125I-alpha/beta. This
      result indicates structural change at the subunit interface in response to hCG
      binding to the receptor.

PMID- 9027348
TI  - Structure and functional significance of the carbohydrates of the LH/CG receptor.
AB  - The LH/CG appears to contain 1-4 bi- or multi-antennary complex-type N-linked
      oligosaccharide side chains, which appear to locate apart from the hormone
      binding regions. The exact sites to which the N-linked chains are attached remain
      to be delineated. The carbohydrates of the mature membrane-inserted receptor do
      not contribute to either specific high-affinity ligand-binding or signal
      transduction of the receptor. Thus, the polypeptide core of the receptor is
      responsible for both high affinity binding and dictating the hormone specificity.
      Moreover, the deglycosylated receptor, once inserted to the plasma membrane in a
      functionally mature form, retains its functional conformation or permits the
      conformational change that is required for coupling of the receptor to effector
      enzymes. Addition of oligosaccharides to the nascent LH/CG receptor but not their
      subsequent conversion to complex-type ones appears to be required for acquiring
      the hormone-binding conformation. On the other hand, neither addition of
      oligosaccharides to the nascent receptor, nor their further maturation are needed
      for the transport of the receptor to the plasma membrane. Thus, one function of
      the N-linked oligosaccharides in the LH/CG receptor appears to be to direct the
      proper folding of the receptor.

PMID- 9027349
TI  - Pathophysiological importance of various molecular forms of human
      choriogonadotropin.
AB  - Human chorionic gonadotropin (hCG), its subunits and fragments are widely used
      for diagnostic purposes. In addition to the diagnosis of pregnancy and pregnancy
      related disorders, hCG determinations are used for diagnosis of trophoblastic and
      recently also nontrophoblastic tumors. The use for diagnosis of nontrophoblastic
      tumors requires highly specific and ultrasensitive assays. With these, it is
      possible to measure the concentrations of both hCG, the free beta-subunits and
      the so called beta-core fragment in healthy subjects. Therefore it is important
      to establish reference values for these and also to be aware of the influence of
      physiological factors on the serum and urine concentrations. Improved
      standardization of the assay methods is also essential for these novel
      applications of hCG determinations to become useful.

PMID- 9027350
TI  - Metabolism of hCG and hLH to multiple urinary forms.
AB  - Human chorionic gonadotropin (hCG) is synthesized primarily in the placenta while
      human luteinizing hormone (hLH) is produced in the pituitary. Both hormones are
      highly homologous in structure and both appear to be altered to analogous
      molecular forms as the hormones are proteolytically processed, or metabolized,
      from tissue of origin, through the circulation, and finally to the urine.
      Placental hCG is excreted into urine as heterodimeric hormone, heterodimeric
      nicked hCG, free subunits (some nicked), and predominantly as the hCG beta core
      fragment. A pituitary form of heterodimeric hCG, which is partly sulfated as is
      pituitary hLH, was recently isolated and is likely the form of hCG observed in
      the urine of healthy postmenopausal women and nonpregnant premenopausal women as
      well. A pituitary form of the hLH beta core fragment, highly analogous in
      structure to that of urinary hCG beta core fragment, has been used to develop
      specific monoclonal antibody assays to measure urinary hLH beta core fragment
      which is excreted at significantly higher molar concentrations than is hLH in the
      urine of ovulating women 1 or 2 days after the LH surge. This fragment of LH
      appears in the urine of postmenopausal women as well. The development of the
      capability to distinguish the hCG beta core fragment from the hLH beta core
      fragment in urine may have useful applications in tumor marker assays, pregnancy
      tests, and menopause. While hCG urinary assays have been widely employed, urinary
      assays for hCG and hLH metabolites are much less used since the urinary molecular
      forms are only partly known. Our studies of hCG and hLH urinary metabolites are
      directed towards improvement of the utility of urinary measurements of molecules
      derived from these hormones. Since many of the molecular forms of these two
      hormones in urine differ from their forms in blood, it may be necessary to
      produce new immunoassays as well as novel urinary reference preparations to
      accurately measure these molecules within their urinary matrix.

PMID- 9027351
TI  - Structural and functional characterisation of hFSH and hLH isoforms.
AB  - Human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) are
      gonadotropins which are secreted as multiple forms by the pituitary. Evidence
      supporting the structural and functional heterogeneity of 15 purified hFSH
      isoforms and 20 purified hLH isoforms from pituitary extracts will be presented.
      Gonadotropin isoforms were purified by a combination of preparative isoelectric
      focusing and ion-exchange chromatography. The protein mass of each isoform was
      determined by amino acid analysis, which also correlated (data for hLH) (r =
      0.999, P < 0.001, n = 15) with the UV area under the curve at 280 nm of the
      isoforms following gel-filtration HPLC. The alpha and beta subunits of FSH and LH
      were shown to be intact by SDS-PAGE under reducing condition, with no evidence of
      proteolytic nicking or presence of contaminating proteins. hFSH radioreceptor
      activity varied over a seven-fold range, and a positive correlation (r = 0.85, P
      < 0.001, n = 9) was observed between FSH receptor activity and the sialic acid
      (SA) content (1.5-13.7 mol SA/mol hFSH) of the isoforms, as determined by an HPLC
      based microfluorometric assay. FSH in vitro activities varied over a similar
      range with a high correlation (r = 0.82, n = 15) with receptor activities,
      suggesting that the initial association of the hormone with the receptor is the
      key interaction with less differences attributed to subsequent effects in the
      signaling pathway. A similar result was seen with the hLH isoforms. To explore
      FSH/LH in vivo, the circulating half-life (LH/FSH) and the in vivo bioactivity
      (LH) using an acute in vivo assay was investigated. The clearance of hLH and hFSH
      showed a bi-exponential pattern for all isoform preparations with the proportion
      of the slower dissociating component (t 1/2 50-60 min) increasing three-fold with
      increasing sialic acid content of the isoform. The more rapidly cleared component
      (t 1/2 approx 10 min) is attributed to hepatically cleared gonadotropin, rather
      than gonadotropin equilibration between body compartments. The in vivo assay
      procedure for LH was based on the 24 h integrated plasma testosterone levels in
      rats following administration of graded doses of hLH isoform or standard. A 16
      fold range in vivo activities between LH isoforms (n = 14) was observed. A
      comparison between hLH in vitro and in vivo activities showed a good correlation
      (r = 0.75) with the slope of the regression line (1.39) not significantly
      different from unity. These results suggest that in this acute in vivo assay
      method, the differences in circulating half-lives between hLH isoforms although
      large is not a key factor in their in vivo activity. However, in chronic in vivo
      assay systems the differences in clearance rates between isoforms may be
      important in their subsequent biological response. It is concluded that
      structural heterogeneity of FSH and LH contributes to functional differences,
      with a key interaction occurring at the receptor level. The contribution of
      sialic acid to these activities was also investigated.

PMID- 9027352
TI  - Inherited disorders of the gonadotropin hormones.
AB  - Inherited disorders of the pituitary gonadotropins, LH and FSH, are rare. No
      mutations of the common alpha-subunit gene have been described. A single case of
      an FSH beta gene mutation has been reported. This mutation consisted of a two
      nucleotide deletion that caused a frameshift of codons 61-86 followed by
      premature termination. A homozygous patient with this mutation presented with
      primary amenorrhea and infertility. Serum FSH levels were low and LH levels were
      elevated. A postmenopausal heterozygous relative had subnormal FSH and LH and it
      was postulated that the mutant FSH beta subunit may have impaired gonadotrope
      function. Only a single example of an LH beta gene mutation has been described.
      This case was reported in a male who failed to undergo puberty, had elevated
      immunoreactive LH, but low bioactive LH and low testosterone. The LH beta gene is
      a member of the CG beta/LH beta gene cluster that resides on chromosome 19q. No
      rearrangements or deletions were observed and there was a homozygous
      substitutions of Gln 54 with Arg. The substituted Gln residue is conserved in
      each of the glycoprotein hormone beta-subunits. Recombinant mutant LH was
      expressed in CHO cells and was shown to be immunologically active, but it did not
      bind to the LH receptor, explaining the absence of bioactivity. This finding
      suggests that Gln 54 is either a contact site for the receptor or that the
      mutation alters the conformation of LH to prevent binding to the receptor. The
      serum LH bio/immuno (B/I) ratio in heterozygotes was 50% of control samples,
      consistent with normal production and stability of the mutant hormone in vivo.
      Male heterozygotes exhibited slightly reduced testosterone and only one of four
      was fertile. Female heterozygotes had regular menses and were fertile. A
      polymorphic variant of LH has been reported. The variant is prevalent in Finland
      (24% heterozygotes) and several cases have been reported in Japan. The LH variant
      consists of two amino acid substitutions (W8R; I15T) that correspond to residues
      normally found in CG beta. The I15T substitution may introduce a glycosylation
      site. The variant LH has increased bioactivity, but a reduced serum half-life. It
      is unclear whether the LH variant is of clinical significance aside from altering
      immunoactivity in some assays. In addition to gonadotropin mutations, defects in
      gonadotrope viability (SF-1; DAX-1 mutations) and in GnRH secretion (Kallmann
      syndrome; SF-1; DAX-1) can also lead to hypogonadotropic hypogonadism (Fig. 1).
      As noted in other talks, the LH-R and FSH-R are also targets for mutations. Thus,
      genetic defects have now been identified at each level of the H-P-G axis.

PMID- 9027353
TI  - Bioassays of gonadotropins based on cloned receptors.
AB  - Because of the microheterogeneities of gonadotropins, immunoreactive measurements
      of gonadotropins do not necessarily reflect their bioactivity. Follicle
      stimulating hormone (FSH) bioassays have relied on measurement of aromatase
      activity in primary cultures of immature rat Sertoli cells or rat granulosa cells
      (GAB assay). Luteinizing hormone (LH) bioassays have relied on measurement of
      androgen production in primary cultures of rat interstitial testicular cells
      (RICT) or mouse Leydig cells. Those bioassays are cumbersome because they rely on
      primary culture and on indirect measurement of estradiol or testosterone by RIAs.
      The cloning of the cDNAs of FSH and LH receptors has allowed the establishment of
      cell lines expressing human receptors. The cotransfection of the recombinant
      gonadotropin receptor with a cAMP reporter gene allows a nonisotopic measurement
      of gonadotropin bioactivity. Furthermore, patient serum can be tested directly
      without prior extraction. We and other groups have developed a CHO cell line
      expressing the human FSH receptor and a luciferase reporter gene (CHO-FSHR). The
      CHO-FSHR assays is specific for FSH and free of serum interference up to a final
      concentration of 20%. The clinical sensitivity is 3 IU/l, the interCV 16%, the
      intraCV 8%. Studies were performed in normal women (n = 11) during the menstrual
      cycle using the CHO-FSHR cells. The ratio of bioactive to immunoactive FSH (B/I)
      equals 1.1 +/- 0.04 across the follicular and early luteal phase. During the mid
      to late luteal phase the mean B/I rises significantly to 1.65 +/- 0.07 (P <
      0.001). Gonadotropin bioassays based on cloned receptors have been used to search
      for immunoglobulins, directed against the FSH or the LH receptors in premature
      ovarian failure patients. No blocking antibodies were found among the 38 women
      studied. A recent study of FSH bioactivity in patients with FSH secreting
      pituitary adenomas shows increased values of the B/I ratio. In summary, cell
      lines expressing the LH and the FSH human receptors are now available. Those
      homologous systems enable clinicians to study potential forms of mutated FSH or
      antibodies directed against gonadotropin receptors. Furthermore, bioassays based
      on cloned receptors are interesting tools to test anti-LH or anti-FSH molecules
      mainly in contraceptive research.

PMID- 9027354
TI  - The LH/CG and FSH receptors: different molecular forms and intracellular traffic.
AB  - Monoclonal antibodies have been raised against the LH/CG receptor [1] and have
      allowed to perform immunochemical studies of the receptor in target cells. Three
      different forms of the LH/CG receptor are physiologically expressed: a mature
      approximately 85 kDa transmembrane species corresponding to the full length
      receptor, a approximately 68 kDa high mannose containing species corresponding to
      a precursor which accumulates inside the cells, and truncated soluble
      approximately 45-48 kDa molecular weight species corresponding to the variant
      messanger RNAs generated by alternative splicing. Monoclonal antibodies against
      the human FSH receptor were also prepared. They allow to observe the existence of
      two forms of the FSH receptor in the ovaries: a major approximately 87 kDa
      species corresponding to the mature receptor and a minor approximately 81 kDa
      species corresponding to a high mannose rich precursor. No variant forms of the
      receptor corresponding to alternative mRNA transcripts were detected. The
      transport of hCG was examined in rat testicular microvasculature by electron
      microscopy and by analyzing the transfer of radiolabeled hormone and antireceptor
      antibodies. LH/CG receptors were present in endothelial cells and were involved
      in hormone transcytosis through these cells. Immunocytochemical experiments have
      shown that the FSH receptor has a polarized expression in the Sertoli cells of
      the testes whereas the LH/Cg receptor is spread on the surface of thecal
      granulosa and luteal cells in the ovary and Leydig cells in the testes. To study
      the mechanism of this polarization FSH, LH and TSH receptors were expressed in
      polarized MDCK cells. The mechanism of basolateral localization and of
      transcytosis of the receptors was studied using this model. The effect of
      hormone, cAMP and agents acting on G proteins was examined.

PMID- 9027355
TI  - Expression of follicle stimulating hormone-receptor mRNA during gonadal
      development.
AB  - Receptors for follicle-stimulating hormone (FSH) are found only in the gonads and
      have been localised to the Sertoli cells of the testis and the granulosa cells of
      the ovary. During gonadal development, functional signal transduction systems are
      present before gonadotrophin receptors appear indicating the expression of the
      receptors is the crucial step in development of gonadal responsiveness to
      gonadotrophins. The FSH receptor gene contains a single large exon which encodes
      the transmembrane and intracellular domains and nine smaller exons which encode
      most of the extracellular domain. In all species studied so far the FSH-receptor
      primary transcript has been shown to undergo alternate splicing. The function of
      these alternate transcripts is unclear but changes in alternate splicing appear
      to be associated with development of receptor mRNA expression. In the rat
      transcripts encoding only the extracellular domain of the receptor are detectable
      2 days before transcripts encoding the full length receptor. In the mouse ovary
      FSH-receptor mRNA levels and alternate splicing has been measured during
      development. Results show that FSH-receptor mRNA is detectable in day 1 ovaries
      which contain only primordial follicles. At this stage mRNA levels are low but a
      significant increase in FSH-receptor mRNA is seen around day 5 when primary
      follicles first appear. This correlates with in situ hybridisation studies which
      first detect FSH-receptor transcripts in primary follicles. At all stages of
      development the level of transcripts encoding the extracellular domain was
      significantly greater than that encoding for the transmembrane and intracellular
      regions suggesting that significant levels of shortened transcripts are produced.
      In the hypogonadal (hpg) mouse which lacks circulating gonadotrophins levels of
      FSH-receptor mRNA appeared normal up to 15 days. This shows that gonadotrophins
      ar not require for development of FSH-receptor mRNA levels. Studies on FSH
      receptor mRNA levels during granulosa cell luteinization show that there is
      complete loss of full-length transcripts soon after luteinization. Transcripts
      encoding the extracellular domain remain present, however, up to at least mid
      cycle. Thus, changes in receptor transcript splicing during loss of FSH-receptors
      appear to mimic, in reverse, changes occurring during development. It may be that
      the FSH-receptor gene is constitutively expressed in follicular (pre-granulosa)
      cells, granulosa cells and granulosa-luteal cells but that control of RNA
      splicing regulates levels of full-length FSH-receptor transcript.

PMID- 9027356
TI  - Functional and clinical consequences of mutations in the FSH receptor.
AB  - The follicle-stimulating hormone (FSH) is essential for normal gametogenesis. In
      females FSH is required for ovarian development and follicle maturation whereas
      in males FSH determines Sertoli cell number and quantitatively and qualitatively
      normal spermatogenesis. FSH action is mediated by a G-protein coupled receptor
      expressed solely in granulosa and Sertoli cells. The FSH-receptor (FSHR) gene is
      localized on chromosome 2 p21 and spans a region of 54 kb. It consists of ten
      exons; exon one to nine encode the large extracellular domain and the
      transmembrane domain is comprised of exon ten. Mutations in the FSHR gene could
      severely affect gametogenesis and result in infertility. Therefore screening
      programs have been initiated, in which patients with disturbed fertility were
      searched for mutations in the FSHR gene. Several Finnish families were identified
      displaying an inherited pattern of ovarian dysgenesis, a disease leading to
      streaky underdeveloped ovaries and primary amenorrhea. By genetic linkage the
      locus of the genetic defect was confined to chromosome 2 p21. Analysis of the
      FSHR gene resulted in the identification of a mutation (Ala189Val) homozygous in
      all affected females. Functional studies revealed that the mutation affects the
      proper protein folding and thereby inactivates the receptor. In a male patient
      hypophysectomized because of a pituitary tumor, who despite undetectable serum
      gonadotropins had normal semen parameters, we hypothesized an activating mutation
      of the FSHR. Screening of exon ten of the FSHR gene resulted in the
      identification of a Asp567Gly transition in the third intracytoplasmatic loop.
      Functional studies resulted in a 1.5-fold increase in basal cAMP production
      compared to wild type FSHR, indicating that the heterozygous mutation leads to a
      ligand-independent constitutive activation of the FSHR. This patient provides an
      exceptional model of nature defining the role of FSH in human spermatogenesis.
      Mutations of the FSHR might have differential effects in each gender. For example
      activating mutations have not been described in women, therefore it is not clear
      whether the constitutive activity of the receptor could disturb normal follicular
      development resulting in certain infertility.

PMID- 9027357
TI  - Pesticides: multiple mechanisms of demasculinization.
AB  - Many pesticides are known to produce reproductive and developmental effects in
      chronically exposed non-target organisms, including humans. Recent evidence
      suggests that demasculinization may be an important mechanism responsible for
      some of these effects. Some pesticides have been shown to interact with the
      androgen receptor and to act as antagonists, while others have been shown to
      interact with the estrogen receptor and function as estrogens in both in vitro
      and in vivo. Many pesticides can also lower serum androgen levels by altering
      rates of synthesis or metabolism. Given the ubiquity of pesticides in the
      environment and the multiple mechanisms whereby they can elicit demasculinizing
      effects, synergy between such compounds may produce clinical endocrine
      dysfunction at current human exposure levels.

PMID- 9027358
TI  - Bovine adrenocortical cells in culture synthesize an ouabain-like compound.
AB  - Ouabain or a closely related isomer, and 'ouabain-like compound' (OLC), has been
      identified in plasma, by Hamlyn et al., using several physico-chemical and
      biological methods. Using a radioimmunoassay, the same authors later
      characterized an identical compound in adrenal cortex tissue and culture medium
      from adrenocortical cells. Nevertheless, other groups, using different
      immunosera, were not able to detect OLC in adrenal cortex and adrenocortical
      cells medium. In this report, we confirm the presence of OLC in bovine adrenal
      cortex and in fasciculata cells culture medium. The compound that we obtained has
      the same chromatographic properties as ouabain on HPLC using two types of elution
      systems. It presents the same mass spectrum and is able to bind to erythrocytes
      membranes Na(+)-K(+)-ATPase. In primary cultures of adrenocortical cells, its
      biosynthesis is increased after addition of pregnenolone or progesterone
      suggesting that these compounds may represent intermediate substrates in the
      biosynthetic pathway. Rhamnose readily enters the adrenocortical cell and
      increases slightly the biosynthesis of OLC. The present studies confirm that
      bovine adrenocortical cells in primary culture release an OLC with no differences
      with authentic ouabain using, HPLC, mass spectrometry and radioreceptor assay and
      suggest that OLC may be a product related to the adrenocortical steroidogenic
      pathway.

PMID- 9027359
TI  - Differential responses to ligands of overexpressed thyroid hormone and retinoid X
      receptors in a Xenopus cell line and in vivo.
AB  - In an attempt to explain the contrasting patterns of expression of Xenopus
      thyroid hormone (xTR) and retinoid X (xRXR) receptor genes and to extend our
      understanding of the role of heterodimerization of these receptors during
      amphibian metamorphosis, we have investigated the response to their respective
      ligands of cells in which xTR and xRXR were overexpressed. Results obtained with
      two separate approaches are now described. In the first, 3,3'5-triiodothyronine
      (t3) was found to strongly upregulate xTR beta mRNA in XTC-2 cells, but not of
      xTR alpha or xRXR alpha mRNAs, while xRXR gamma transcripts could not be
      detected. 9-cis-retinoic acid (9-cis-RA) did not substantially influence the
      expression of any of these four receptor genes. When transcription from three
      different thyroid response elements (TREs) (a palindromic TREpal, an inverted
      repeat +6 [F2] and a direct repeat +4[DR+4] as present in the promoter of xTR
      beta gene) was measured in XTC-2 cells in which xTR beta and xRXR alpha were
      overexpressed, only T3 upregulated transcription while 9-cis-RA, alone or
      together with T3, was ineffective. 9-cis-RA however enhanced transcription from
      an RXR responsive element (RXR-RE). THe second approach involved overexpression
      of xTR beta and xRXR alpha in premetamorphic Xenopus tadpole tail muscle followed
      by measuring the response of the tails to T3 in organ culture. After validating
      the microinjection/culture procedure histochemically, we found that T3 enhanced
      transcription from the xTR beta DR +4 TRE in tails in which xTR beta was
      overexpressed but the overexpression of xRXR alpha failed to modify this
      response. It is concluded that in both XTC cells and tadpole tails, overexpressed
      xRXR fails to modify the enhanced transcriptional response of endogenous and
      overexpressed xTR beta to T3 and that exogenous 9-cis-RA is ineffective.

PMID- 9027360
TI  - Estradiol activates p60src, p53/56lyn and renatured p50/55 protein tyrosine
      kinases in the dog prostate.
AB  - Protein tyrosine kinases (PTKs) are key enzymes implicated in signal transduction
      pathways regulated by growth factors (GFs). We have previously shown by
      immunohistochemistry that the level of phosphotyrosine (pY) proteins is increased
      in prostatic basal epithelial cells following estrogen treatment in castrated
      dogs. In this study, we investigated if this treatment increases the level and
      distribution of prostatic PTK activity, and more specifically, if it alters the
      expression and/or activity of the Src family members p60src and p53/56lyn.
      Prostates from normal and hyperplastic dog prostates, as well as those from
      castrated dogs treated with androgens, were also examined. Only the glands
      obtained from estrogen-treated dogs had a significantly increased total and
      specific PTK activity, observed uniquely in the particulate extract, as compared
      to the other types of prostates studied. In addition, this increased activity was
      correlated upon gel filtration chromatography with the presence of an additional
      peak of activity with an apparent molecular weight of 130 kDa, which was absent
      in other prostate fractions presenting only 50 kDa peaks. Using antibodies, we
      demonstrate that active p60src and pp53/56lyn kinases accounted for 81% of the
      activity in this 130 kDa peak. On the other hand, in situ renaturation also
      revealed the presence of still uncharacterized 50/55 kDa PTKs in the 130 kDa
      peak. Altogether, these findings raise the possibility that these PTKs contribute
      to the transmission of mitogenic signals originating directly or indirectly from
      estrogen stimulation of the basal cell layer of the prostate.

PMID- 9027361
TI  - Hepatic lipase gene expression is transiently induced by gonadotropic hormones in
      rat ovaries.
AB  - Hepatic lipase (HL) gene expression was studied in rat ovaries. A transcript
      lacking exons 1 and 2 could be detected by reverse transcription-polymerase chain
      reaction (RT-PCR) in the ovaries of mature cyclic females and of immature rats
      treated with pregnant mare serum followed by human chorionic gonadotropin (hCG)
      to induce superovulation. By competitive RT-PCR the HL transcript was quantified.
      Low levels of HL mRNA were detected in ovaries of mature cyclic females and of
      immature rats. During superovulation HL mRNA was several fold higher than in
      mature cyclic rats and transiently increased to a maximum at 2 days after hCG
      treatment. Pulse-labelling of ovarian cells and ovarian slices with
      [35S]methionine followed by immunoprecipitation with polyclonal anti-HL IgGs
      showed de novo synthesis of a 47 kDa HL-related protein. Expression of the
      protein was transiently induced by gonadotropins with a peak at 2 days after hCG
      treatment. Induction of liver-type lipase activity occurred only after HL mRNA
      and synthesis of the HL-related protein had returned to pre-stimulatory levels.
      We conclude that in rat ovaries the HL gene is expressed into a variant mRNA and
      a 47 kDa protein. The expression of the HL gene in ovaries is inducible and
      precedes the expression of the mature, enzymatically active liver-type lipase.

PMID- 9027362
TI  - Expression of amphiregulin in the sheep mammary gland.
AB  - The reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify,
      from sheep mammary gland total RNA, a 280 bp sequence of amphiregulin cDNA.
      Cloned and sequenced, it corresponded to the 78 amino acids of the major secreted
      form of amphiregulin, showing 81, 70 and 69% identity with human, rat and mouse
      amphiregulin, respectively. Expression of amphiregulin was detected by RT-PCR in
      the mammary gland at several developmental stages (fetal, lamb, early and late
      pregnant and lactating ewes) and in isolated myoepithelial cells. By Western
      blotting with an antiserum to human amphiregulin, two molecular weight forms, 27
      and 51 kDa were detected in sheep mammary gland microsomal preparations, in a
      mammary gland extract after heparin affinity chromatography and in a medium
      conditioned by mammary epithelial cells. By immunocytochemistry, amphiregulin was
      detected in the cytoplasm and nuclei of luminal epithelial cells, myoepithelial
      cells and in intralobular stroma. An autocrine/paracrine role in sheep mammary
      growth is indicated.

PMID- 9027363
TI  - Effects of chronically elevated growth hormone levels on polyamine metabolism in
      elderly transgenic mice.
AB  - The polyamines are ubiquitous, multifunctional aliphatic amines with roles in
      cell growth, proliferation, differentiation, and malignant development. After
      growth stimulation, rapid and transient changes occur in polyamine regulatory
      enzymes. In this respect, acute effects of growth hormone (GH) injection on
      polyamine metabolic enzymes have earlier been shown. The present investigation
      comprises studies of the effects on polyamine metabolism of constitutively
      elevated levels of circulating GH in elderly transgenic (tg+) mice,
      overexpressing bovine GH. Polyamine levels were found to be constitutively
      altered in the liver and kidney of tg+ mice. Less changes were found in the
      spleen and none in the brain. The cellular uptake of polyamines in the liver from
      tg+ mice showed an increase and considerable changes were observed in the
      activity of ornithine decarboxylase (ODC) in the liver and kidney and S
      adenosylmethionine decarboxylase (AdoMetDC) in the liver. A conspicuous finding
      was the distribution pattern of ODC protein in the liver and both tg- and tg+
      animals. The results show that the effects of chronically elevated GH levels are
      organ-dependent and complex, and differ from acute GH effects. Despite high ODC
      activity and polyamine levels in liver, these mice did not display any malignant
      transformation even at an advanced age, indicating that high ODC activity is not
      sufficient to induce tumorigenesis in vivo.

PMID- 9027364
TI  - Androgen-dependent cell cycle arrest and apoptotic death in PC-3 prostatic cell
      cultures expressing a full-length human androgen receptor.
AB  - To assess the function of androgen receptor in androgen-independent prostate
      cancer cells, human PC-3 prostate carcinoma cells, which lack androgen receptor
      (AR) expression, were transfected with a full length human AR cDNA sequence
      inserted into an episomal expression vector system. Several clonal lines of
      transfected cells expressing varying levels of a 110 kDa AR, as determined by
      immunoblotting and ligand binding assay, were isolated. The expressed ectopic
      receptors displayed nuclear binding following androgen treatment and mediated
      androgen inducibility of a mouse mammary tumor virus (MMTV)-luciferase reporter
      gene construct in a dose-dependent manner. 5 alpha-dihydrotestosterone (DHT)
      activation of luciferase activity was blocked by the AR antagonist
      hydroxyflutamide, and was promoter-specific based on the inability of the hormone
      insensitive RSV promoter to respond to DHT. Treatment of AR-expressing PC-3 cells
      with physiological levels of DHT for 3 days resulted in paradoxical inhibition of
      cell growth. The growth-inhibitory effect was observed in clonal lines expressing
      low, moderate and high levels of AR, indicating that it was not the result of AR
      overexpression. To determine whether AR-expressing PC-3 cells had become androgen
      dependent, albeit with slowed growth, the effect of 1.0 nM DHT on the growth of
      two clonal lines expressing low and moderate receptor levels (PC-3(AR)13 and PC
      3(AR)2, respectively) was examined on over an 18 day period. DHT removed after 3,
      6, or 9 days and replaced with steroid-free medium. Surprisingly, after 6 days of
      DHT treatment, the number of PC-3(AR)2 cells began to decrease such that all
      cells were dead by 15 days after initiation of DHT treatment. A similar effect
      was observed in PC-3(AR)13 cells, but required a longer initial period of DHT
      exposure. PC-3(AR)2 cells were rescued from cell death if DHT was withdrawn 3
      days but not 6 or 9 days after initiation of DHT treatment. As determined by DNA
      cell cycle analysis, the proportion of cells in the G1 phase was enhanced by DHT
      treatment, accompanied by a decrease in cells in the S and G2M phase of the cell
      cycle. After 6 days of DHT treatment, the proportion of cells in G1 decreased
      which was accompanied by an increase in cells in a subG1 population consistent
      with apoptosis. DNA fragmentation in PC-3(AR)2 cells after 3 or 6 days of DHT
      treatment was demonstrated by agarose gel electrophoresis, further indicating the
      cell death was apoptotic. Removal of DHT from PC-3(AR)2 cultures after 3 days,
      but not after 6 or 9 days, was followed by a large shift in cells from G1 to S
      and G2M. These data suggest that DHT blocks the progression of AR transfected PC
      3 cells through the cell cycle, resulting in growth inhibition and apoptosis.

PMID- 9027365
TI  - Cloning, expression and regulation of the human S14 gene.
AB  - The rat S14 gene has been a useful model to study carbohydrate and
      triiodothyronine (T3) regulation of hepatic gene expression. To gain insight into
      the regulation and function of the S14 gene, we isolated the human S14 gene and
      studied its sequence, tissue specific expression, and transcriptional regulation
      by glucose and T3. The deduced amino acid sequence of the human S14 protein is
      78% identical to that of the rat. Northern blot analysis showed that the S14-mRNA
      is a single species in human liver and is not present in human brain or HepG2
      cells. Transfection studies in primary hepatocytes revealed that transcription of
      the human S14 gene is regulated by glucose and T3 in a similar manner to that of
      the rat gene. However, in HepG2 cells, T3 and glucose did not affect the
      transcription of the human S14 gene. These observations suggest that the S14 gene
      is highly conserved in mammals and is similarly regulated by carbohydrate and T3
      in vivo. More importantly, the function of the human S14 gene may be critical in
      lipid metabolism in human liver as the rat S14 gene is in rodents.

PMID- 9027366
TI  - Vitamin D receptor content and transcriptional activity do not fully predict
      antiproliferative effects of vitamin D in human prostate cancer cell lines.
AB  - Prostate cancer cell lines exhibit variable growth suppression by the hormonal
      form of vitamin D3, 1,25-Dihydroxyvitamin D3 [1,25 (OH)2D] (1,25 D3). To
      understand the molecular basis for this differential sensitivity to 1,25 D3, we
      compared growth response to 1,25 d3, vitamin D receptor (VDR) content and VDR
      transcriptional activity in four well-characterized human prostate cancer cell
      lines: LNCaP, DU145, PC-3 and ALVA-31. In PC-3 and DU145 cells, relative lack of
      growth inhibition by 1,25 D3 (< 10% inhibition) correlates with very low levels
      of VDR (9-15 fmol/mg protein) compared to classical vitamin D3 target tissues
      (approximately 75-200 fmol/mg protein). Transfection of DU145 and PC-3 cells with
      a VDR cDNA expression vector is sufficient to establish growth sensitivity to
      1,25 D3, suggesting that low VDR levels are responsible for the failure of these
      cell lines to respond to 1,24 D3. LNCaP cells are highly sensitive to growth
      inhibition by 1.25 D3 (approximately 55% inhibition) and contain approximately 2
      3-fold more VDR (25 fmol/mg) than the relatively 1,25 D3-insensitive PC-3 and
      DU145 cell lines. However, ALVA-31 cells display less than 20% growth inhibition
      to 1.25 D3 although they contain the highest levels of VDR (45 fmol/mg) of the
      four cell lines. Thus, sensitivity to growth inhibition by 1,25 D3 does not
      correlate with VDR content in ALVA-31 and LNCaP cells. This lack of correlation
      between VDR density and growth responses to 1,25 D3 led us to investigate VDR
      mediated gene transcription in these cell lines. We employed two different
      naturally occurring vitamin D response elements (VDREs) linked to a reporter
      gene. Reporter gene activation by 1,25 D3 correlated well with VDR content in all
      four cell lines. Therefore, compared to LNCaP cells, decreased sensitivity of
      ALVA-31 to growth inhibition by 1,25 D3 is not due to a decrease in the general
      transcriptional activity of VDR. We conclude that growth inhibition by 1,25 D3 in
      prostate cancer cells requires VDR but that this response is modulated by non
      receptor factors that are cell line-specific.

PMID- 9027367
TI  - Src tyrosine kinase activity in rat thecal-interstitial cells and mouse TM3
      Leydig cells is positively associated with cAMP-specific phosphodiesterase
      activity.
AB  - Phosphodiesterases (PDEs) play a critical role in the regulation of intracellular
      cyclic nucleotide concentration and, consequently, regulate the state of cellular
      differentiation. We have reported that the Src-selective tyrosine kinase
      inhibitor, herbimycin A, potentiates luteinizing hormone (LH)-stimulated cAMP
      accumulation in culture media by ovarian thecal-interstitial cells (TIC; see
      Taylor, C and Terranova, P.F. (1995) Lipopolysaccharide inhibits rat ovarian
      thecal-interstitial cell steroid secretion in vitro. Endocrinology 136, 5527
      5532). The present study was conducted to investigate the effects of herbimycin,
      and changes in Src tyrosine kinase activity, on PDE activity in rat TIC an in the
      mouse TM3 Leydig cell line. Treatment of TIC with herbimycin (1 microM) for 24 h
      inhibited basal and LH-stimulated PDE activity (approximately 50 and 70%,
      respectively) and was associated with an increase in cAMP and progesterone
      accumulation in culture media. Treatment of TM3 cells with herbimycin inhibited
      PDE activity and increased cAMP accumulation in a dose- and time-dependent
      manner. TM3 cell cultures challenged with herbimycin had lower Src tyrosine
      kinase activity than controls (approximately 50%); however, protein kinase A
      activity was unaffected. TM3 cells stably transfected with a dominant negative
      Src tyrosine kinase (TM3Srck-) had lower PDE activity than cells transfected with
      a G418 resistance gene alone (TM3pSV2neo) which served as control cells.
      Conversely, TM3 cells expressing a temperature-sensitive Src kinase had
      significantly greater PDE activity at the Src active temperature (35 degrees C;
      the temperature at which the enzyme is active) than TM3pSV2neo control cells
      grown at the same temperature. TM3 cell lysates hydrolyzed minimal amounts of
      cGMP, indicating a cAMP-specific PDE. Phosphodiesterase activity in both TM3 and
      rat TIC was sensitive to the PDE4-selective inhibitor RO20-1724, indicating the
      predominant active enzyme is probably a member of the cAMP-specific PDE4 family.
      From the present data, we conclude that a tyrosine kinase of the Src family may
      play an important role in regulating phosphodiesterase activity in thecal and
      Leydig cells, and thus regulate intracellular cAMP and the state of cellular
      differentiation.

PMID- 9027368
TI  - Tissue-specific regulation by vitamin D3 of a novel protein containing ankyrin
      like repeats.
AB  - Vitamin D3 is the precursor of the steroid hormone 1,25-dihydroxyvitamin D3 which
      is involved in the regulation of calcium metabolism, growth and differentiation.
      We used differential display of mRNA populations from kidney and intestine of
      vitamin D3-deficient and -replete chicks to determine the steady-state abundance
      of approximately 5000 mRNAs. One of these sequences, whose differential
      expression in kidney and down-regulation by vitamin D3 was confirmed by Northern
      analysis, was used to screen a cDNA library from vitamin D3-deficient chick
      kidney in order to obtain a full length cDNA. Subcloning and sequencing revealed
      that this cDNA encodes a novel protein containing ankyrin-like repeats and a C
      terminal Fe-S binding region signature. The encoded protein consists of 617 amino
      acids and contains two sets of four ankyrin-like repeats separated by 146 amino
      acids. This motif consists of approximately 33 amino acids containing a highly
      conserved central hydrophobic alpha helix and is abundant in a wide variety of
      proteins, particularly those participating in the protein-protein or protein
      membrane interactions involved in signal transduction, regulation of the cell
      cycle and control of transcription. Outside of the ankyrin-like domains, no
      homologies with other proteins in existing data bases were found. Our results
      have revealed a novel protein containing ankyrin-like repeats tissue-specifically
      down-regulated by vitamin D3 in the kidney.

PMID- 9027370
TI  - Referential cohesion and logical coherence of narration after right hemisphere
      stroke.
AB  - A group with right hemisphere dysfunction was compared to neurologically intact
      controls regarding the referential cohesion and logical coherence of narrative
      production. A somewhat varied sample of six stories was obtained with tasks of
      cartoon-elicited story-telling and auditory-oral retelling. We found deficits in
      the patient group with respect to referential cohesion, logical coherence, and
      accuracy of narration, but the occurrence of deficits depended on the condition
      in which narration was produced and, to some extent, on the particular story used
      in each condition. The primary implications of this study pertain to the
      attention given by researchers to the feature of discourse production being
      studied.

PMID- 9027369
TI  - Fractionating the articulatory loop: dissociations and associations in
      phonological recoding in aphasia.
AB  - This paper uses neuropsychological data to differentiate between three models of
      verbal short-term memory (Baddeley, 1983, 1986; Besner, 1987; Monsell, 1987). The
      focus is on three tasks: homophone judgments, rhyme judgments and pseudohomophone
      detection. When lesioned each model predicts characteristic patterns of
      impairment across these tasks. Thirteen span impaired aphasic subjects were
      assessed on all three tasks. The patterns of performance unequivocally supported
      the model proposed by Monsell (1987) which distinguishes input and output
      phonological buffers. Implications for further research are discussed.

PMID- 9027371
TI  - Surface dyslexia in nonfluent progressive aphasia.
AB  - This article presents the case of a 59-year-old male, JH, with a 6-year history
      of primary progressive aphasia (PPA), a disorder characterized by isolated
      language deterioration with relative preservation of other cognitive abilities.
      JH also shows typical features of surface dyslexia, a reading disorder
      exemplified by the selective preservation of phonological reading. One recent
      theory is that surface dyslexia in individuals with PPA results from a loss of
      semantic knowledge. In this paper we consider an additional possibility and
      present data supporting the notion that surface dyslexia may also arise from the
      malfunction in the links between semantic representations and phonology. JH has
      remarkably preserved lexical semantic knowledge when assessed on tasks that do
      not require verbal output. Further, item-by-item comparisons of his oral reading
      and comprehension ability show no significant correspondence between his reading
      and semantic knowledge. These findings lead us to conclude that, in JH's case,
      the surface dyslexia is attributable not to a semantic deficit per se but rather
      to the inability to access phonological information from semantics. JH's language
      profile is considered in relation to potential sources of surface dyslexia and
      other cases of progressive aphasia.

PMID- 9027373
TI  - The modality-specific organization of grammatical categories: evidence from
      impaired spoken and written sentence production.
AB  - We describe the case of a brain-damaged individual whose speech is characterized
      by difficulty with practically all words except for elements of the closed class
      vocabulary. In contrast, his written sentence production exhibits a complementary
      impairment involving the omission of closed class vocabulary items and the
      relative sparing of nouns. On the basis of these differences we argue: (1) that
      grammatical categories constitute an organizing parameter of representation
      and/or processing for each of the independent, modality-specific lexicons, and
      (2) that these observations contribute to the growing evidence that access to the
      orthographic and phonological forms of words can occur independently.

PMID- 9027372
TI  - Semantic memory impairment does not impact on phonological and orthographic
      processing in a case of developmental hyperlexia.
AB  - Recent evidence from patients with progressive language disorders and dementia
      has been used to suggest that phonological and orthographic processing depend on
      intact semantic memory. These claims challenge the traditional view that there
      are functionally separate modules in the language system. The effect of a severe,
      but nonprogressive, semantic impairment on phonological and orthographic
      processing was evaluated in LA, a mentally retarded child with hyperlexia.
      Knowledge of a word's meaning did not affect LA's word repetition, a measure of
      phonological processing, or his acquisition and retention of orthographic
      patterns for writing to dictation low-frequency words with exceptional spellings.
      These findings support the assertion that both orthographic and phonological
      whole-word representations can be acquired, stored, and retrieved in the absence
      of a functional link to semantic memory.

PMID- 9027374
TI  - Semantic priming in Broca's aphasics at a short SOA: no support for an automatic
      access deficit.
AB  - This study tests the recent claim that Broca's aphasics are impaired in automatic
      lexical access, including the retrieval of word meaning. Subjects are required to
      perform a lexical decision on visually presented prime target pairs. Half of the
      word targets are preceded by a related word, half by an unrelated word. Primes
      and targets are presented with a long stimulus-onset-asynchrony (SOA) of 1400
      msec and with a short SOA of 300 msec. Normal priming effects are observed in
      Broca's aphasics for both SOAs. This result is discussed in the context of the
      claim that Broca's aphasics suffer from an impairment in the automatic access of
      lexical-semantic information. It is argued that none of the current priming
      studies provides evidence supporting this claim, since with short SOAs priming
      effects have been reliably obtained in Broca's aphasics. The results are more
      compatible with the claim that in many Broca's aphasics the functional locus of
      their comprehension deficit is at the level of postlexical integration processes.

PMID- 9027375
TI  - Cognitive impairment in Schwartz-Jampel syndrome: a case study.
AB  - Schwartz-Jampel syndrome (SJS) is a rare, hereditary neuromuscular disorder. The
      prevalence of mental retardation has been estimated at 25%, however, no etiologic
      cause has been described. Neuropsychologic and speech language evaluations of an
      8-year-old boy with SJS showed a developmental language disorder and attention
      deficit disorder. He performed in the impaired range on linguistic/sequential
      information processing tests while performing in the average range in
      visuoperceptual and nonverbal tests of intelligence and memory. These results
      suggest further investigation of the cognitive and language functioning of
      patients with SJS.

PMID- 9027376
TI  - Auditory P3 responses to name stimuli.
AB  - Auditory evoked potentials (AEPs) were recorded from 10 normal adults in response
      to their own first names and to other first names spoken on tape. The following
      experimental conditions were used: 30 repetitions of the subject's first name; 80
      other assorted first names from the same gender; 30 repetitions of a first name
      other than the subject's name. A P3 component was recorded from all ten subjects
      in response to their own first name, but not to other first names. Utility of
      this procedure could include assessment of cognitive processing of nonresponsive
      populations such as comatose patients, stroke patients, demented patients,
      autistics, infants, and children.

PMID- 9027377
TI  - The temporal control of repetitive articulatory movements in Parkinson's disease.
AB  - Recent clinical data indicate that internal cueing mechanisms required for the
      triggering of movement sequences are impaired in Parkinson's disease (PD).
      Nevertheless, most PD subjects produce maximal syllable repetition rates similar
      to those observed in healthy control individuals during oral diadochokinesis
      tasks. There is some evidence that tremor oscillations may pace repetitive
      movements in Parkinsonians giving rise to hastening phenomena. Conceivably, the
      performance of PD patients in syllable repetition tasks thus reflects a specific
      timing deficit, i.e., articulatory hastening. It is the aim of the present study
      to investigate the contribution of speech hastening to oral diadochokinesis in
      the presence of internal and external cues. By means of an optoelectric movement
      analysis system, the displacements of the lips during repetitions of the syllable
      /pa/ were recorded in two akinetic-rigid PD individuals. Subjects were asked to
      synchronize labial diadochokinesis to sequences of periodic acoustic stimuli (2.5
      6 Hz). One of the PD patients showed speech hastening, i.e., he produced
      repetitions of 8 to 9 Hz whenever stimulus frequencies exceeded 4 Hz. The other
      Parkinsonian adequately matched the stimulus frequencies required. However, she
      achieved a higher diadochokinesis rate in the matching task than under the
      instruction to repeat "as fast as possible." Thus, the presence of an external
      cue improved performance. In conclusion, our data indicate two deficits of the
      temporal control of repetitive articulatory gestures in PD: speech hastening and
      impaired self-paced sequencing. These two pathomechanisms may allow to reconcile
      the controversial findings on oral diadochokinesis in PD reported so far.

PMID- 9027378
TI  - Temporal profile of microglial response following transient (2 h) middle cerebral
      artery occlusion.
AB  - We measured the time-dependent morphological changes of microglial cells reacting
      to ischemic cell damage after transient (2 h) middle cerebral artery occlusion in
      the rat by means of lectin histochemistry with the B4-isolectin from Griffonia
      simplicifolia as well as immunohistochemistry with monoclonal antibodies directed
      against monocyte/microphage (ED1) and major histocompatibility complex (MHC)
      class II (OX-6) antigens. As early as 1 h after onset of reperfusion, microglia
      were absent in the severely neuronal damaged preoptic area. However, ameboid-like
      microglia were evident in an adjacent area containing scattered shrunken neurons.
      Rod, round and ameboid-like microglia were present in the ischemic lesion between
      2 to 10 h of reperfusion. Round and ameboid cells became predominant in the
      ischemic core lesion and were mingled with highly ramified microglia to the
      boundary at 22 h of reperfusion. Highly ramified microglia were found in an
      adjacent area containing morphologically intact neurons. Round and ameboid cells
      were localized to the inner boundary of the ischemic lesion surrounding the
      infarct zone at 46 of reperfusion. Round and ameboid cells were present
      throughout the entire ischemic lesion in the infarct zone from 70-166 h of
      reperfusion. A marked increase in number and in intensity of highly ramified
      microglial cells were present in the outer boundary of the lesion during this
      period. In addition, a significant increase in both ED1- and OX-6-immunoreactive
      cells in the ischemic region was detected after 10 h of reperfusion and persisted
      up to 166 h of reperfusion. These data demonstrate that microglia exhibit a time
      dependent change in morphology after reperfusion and that the severity of injury
      may be reflected in the state of microglial activation.

PMID- 9027379
TI  - Suramin disrupts insulin-like growth factor-II (IGF-II) mediated autocrine growth
      in human SH-SY5Y neuroblastoma cells.
AB  - Suramin, traditionally used in the treatment of trypanosomiasis, is under
      investigation in the treatment of cancer. One side effect that limits its use is
      the onset of a sensorimotor polyneuropathy. In order to investigate the mechanism
      by which suramin induces polyneuropathy, we examined its effects on SH-SY5Y human
      neuroblastoma cells, an in vitro model of neuronal growth and differentiation.
      Addition of 50-400 micrograms/ml suramin to SH-SY5Y cells grown in 0.6% CS
      inhibited [3H]thymidine ([3H]TdR) incorporation and cell growth. Upon removal of
      suramin, [3H]TdR incorporation increased, demonstrating that levels of suramin
      used were cytostatic and not cytotoxic. Analysis of suramin-treated SH-SY5Y cells
      by flow cytometry revealed growth arrest in the G1/G0 phase of the cell cycle.
      IGF-II-induced SH-SY5Y growth is mediated by the type I IGF receptor (IGF-IR).
      Therefore, we examined its effect on IGF-IR tyrosine phosphorylation. Suramin
      prevented IGF-II-stimulated IGF-IR tyrosine phosphorylation. These results
      indicate that in SH-SY5Y cells, suramin acts as a cytostatic agent and can block
      IGF-II-dependent cell growth by preventing IGF-IR activation. Thus, suramin
      toxicity in the peripheral nervous system may be due, in part, to preventing IGF
      and other growth factors from activating their receptors.

PMID- 9027380
TI  - T2*-weighted magnetic resonance imaging of cerebrovascular reactivity in rat
      reversible focal cerebral ischemia.
AB  - Cerebrovascular carbon dioxide (CO2) reactivity is an important hemodynamic index
      in cerebrovascular disease. In the present study T2*-weighted magnetic resonance
      image (T2* WI) was evaluated as a non-invasive method to investigate changes in
      CO2 reactivity. Fourteen rats were subjected to permanent or, 30 and 90 min of
      temporary middle cerebral artery occlusion. A series of T2* WIs and diffusion
      weighted magnetic resonance images (DWI) was performed hourly under normo- and
      hypercapnic conditions. Triphenyltetrazolium chloride (TTC) staining of brain
      sections was obtained at the end of experiment to evaluate ischemic damage.
      During ischemia, a 4-6% signal increase upon hypercapnia was observed on T2* WI
      in the non-ischemic hemisphere, while no such reactivity was seen in the putamen
      and cortex ipsilateral to the MCA occlusion. After reperfusion, CO2 reactivity
      recovered in the putamen and cortex in the 30 min ischemia group and in the
      cortex alone of the 90 min ischemia groups. The areas with irreversible CO2
      reactivity dysfunction coincidentally revealed no recovery on DWI and lack of TTC
      staining. The results indicate that T2* WI can be used to monitor changes in CO2
      reactivity after various ischemic insults that may indicate tissue viability.

PMID- 9027381
TI  - Modulation of catecholamine release by alpha 2-adrenoceptors and I1-imidazoline
      receptors in rat brain.
AB  - The physiological and pharmacological effects of imidazoli(di)ne derivatives,
      such as clonidine, have been related not only to the interaction with alpha 2
      adrenoceptors but also to their activity on non-adrenoceptor sites termed
      imidazoline receptors. The modulation of catecholamine release by imidazoline
      drugs was studied by monitoring extracellular levels of norepinephrine (NE),
      dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      with microdialysis in cingulate cortex of rats, with or without irreversible
      alpha 2-adrenoceptor blockade. NE and DA levels were in the 1 nM range whereas
      DOPAC and HIVA levels were approximately equal to 100 nM. NE and DA levels were
      increased when the uptake blocker desipramine (1 microM) or KCl (100 mM) were
      added to the perfusion medium. Clonidine induced a dose-dependent (0.3-1.2 mg/kg
      i.p.) decrease in NE (max 61%) and DA (max 40+) levels that was reversed by the
      alpha 2-adrenoceptor antagonist RX821002. After alpha 2-adrenoceptor irreversible
      blockade with the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
      (EEDQ), [3H]clonidine binding to alpha 2-adrenoceptors was reduced by 94 +/- 1%.
      Under such conditions, clonidine elicited a paradoxical dose-dependent (0.6-2.4
      mg/kg i.p.) increase of NE (max 56%) without modifications in DA, DOPAC and HVA
      levels. The stimulatory effect of clonidine was prevented by the imidazoline
      receptor antagonist idazoxan (10 mg/kg i.p.) but not by RX821002 (5 mg/kg i.p.).
      In rats pretreated with EEDQ, cirazoline (I1/I2-imidazoline receptor agonist),
      moxonidine (I1-imidazoline receptor agonist), but not guanabenz (I2-imidazoline
      receptor agonist) (1.2-2.4 mg/kg i.p.) elicited an increase of NE levels in a
      similar manner to clonidine (11-82%). Idazoxan also abolished these responses to
      cirazoline or moxonidine. In contrast to systemic administration, local perfusion
      of clonidine (10-100 microM) through the microdialysis probe under alpha 2
      adrenoceptor alkylating conditions, did not modify extracellular levels of NE and
      DA suggesting an indirect mechanism. The results demonstrate that clonidine and
      related imidazoli(di)ne drugs are able not only to inhibit NE release in rat
      cerebral cortex involving an alpha 2-adrenoceptor mechanism, but also to induce a
      paradoxical NE release through an indirect extracortical mechanism. The findings
      evidence that the indirect modulation of NE levels by imidazoline drugs is mainly
      due to a functional activity on I1-imidazoline receptors.

PMID- 9027382
TI  - The N-methyl-D-aspartate (NMDA) receptor glycine site antagonist ACEA 1021 does
      not produce pathological changes in rat brain.
AB  - ACEA 1021 is a potent, selective N-methyl-D-aspartate (NMDA) receptor glycine
      site antagonist under clinical evaluation as a neuroprotectant for stroke and
      head trauma. The potential of ACEA 1021 to produce morphologic changes in
      cerebrocortical neurons of the rat was assessed since it is known that
      noncompetitive (e.g., MK-801) and competitive (e.g., CGS 19755)NMDA receptor
      antagonists produce neuronal vacuolization and necrosis in the rat posterior
      cingulate/retrosplenial cortex. Male and female adult rats were treated
      intravenously with either vehicle (Tris) or 10 mg/kg or 50 mg/kg ACEA 1021. MK
      801 (5 mg/kg, s.c.) served as positive control. Whereas MK-801 produced
      characteristic neuronal vacuolization and necrosis in the posterior
      cingulate/retrosplenial cortex, neither dose of ACEA 1021 had any effect on
      neuronal morphology. The absence of neuropathological changes in rats supports
      the further clinical evaluation of ACEA 1021 for stroke and head trauma, and
      suggests that glycine site antagonists may be devoid of neurotoxic potential.

PMID- 9027384
TI  - L-arginine ameliorates recirculation and metabolic derangement in brain ischemia
      in hypertensive rats.
AB  - The effects of L-arginine (a precursor of nitric oxide, NO) on cerebral blood
      flow (CBF), cerebrovascular resistance (CVR) and metabolites in the ischemic
      brain were examined in spontaneously hypertensive rats with bilateral carotid
      artery occlusion for 30 min followed by 60 min-recirculation. The administration
      of L-arginine (300 mg/kg, i.v.) increased the CBF by an average of 11 ml x 100 g
      1 x min-1 (P < 0.05 vs. at rest), and N(omega)-nitro-L-arginine (L-NNA, an
      inhibitor of NO synthase, 5 mg/kg, i.v.) reduced the CBF by 5-6 ml x 100 g-1.min
      1 with increase in the mean arterial pressure by 26 mmHg. During ischemia the CBF
      significantly decreased to below 8% of the resting values in all rats. The
      largest blood flow in postischemic hyperemia was 171 +/- 9% of the resting CBF in
      the rats with L-arginine (P < 0.05 vs. L-NNA and saline), followed by 126 +/- 5
      with saline and 109 +/- 3 with L-NNA. The CVR at 60 min of recirculation was
      3.291 +/- 0.144 mmHg . ml-1. 100 g-1 .min-1 in the rats with saline, remained low
      level of 2.711 +/- 0.124 with L-arginine (P < 0.01 vs. L-NNA and P < 0.05 vs.
      saline) and in contrast, significantly increased to 5.732 +/- 0.184 with L-NNA (P
      < 0.01 vs. L-arginine and saline, respectively). Tissue lactate with saline
      increased 2.3-fold at 60 min of recirculation, whereas the increase was inhibited
      to 1.4-fold after L-arginine treatment (P < 0.01 vs. L-NNA) and in contrast,
      significantly increased 5.7-fold with L-NNA. The ATP and glucose levels were
      better preserved in the rats with L-arginine than in those with L-NNA or saline.
      These findings support that the enhanced postischemic hyperemia is beneficial to
      the ischemic brain and the administration of L-arginine may be potentially useful
      for the treatment of acute stroke.

PMID- 9027383
TI  - The glycine site of the NMDA receptor contributes to neurokinin1 receptor agonist
      facilitation of NMDA receptor agonist-evoked activity in rat dorsal horn neurons.
AB  - We have investigated the role of the glycine recognition site of the N-methyl-D
      aspartate receptor (the GlyNMDA site) in the facilitation of NMDA receptor
      agonist-evoked activity in rat dorsal horn neurons that is brought about by
      neurokinin1 (NK1) receptor agonist and the contribution of protein kinase C (PKC)
      activation to this phenomenon. Ionophoresis of the selective NMDA receptor
      agonist 1-aminocyclobutane-cis-1,3-dicarboxylic acid (ACBD) produced a sustained
      increase in the firing rate of single laminae III-V neurons recorded
      extracellularly using multibarrelled glass electrodes. The highly selective NK1
      receptor agonist acetyl-[Arg6,Sar9,Met(O2)11]-SP6-11 (Sar9-SP) greatly
      facilitated this response, but under the present conditions had no effect when
      applied alone or with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptor agonist) at the same current. In the presence of the GLyNMDA site
      antagonists 2-carboxy-4,6-dichloro-(1H)-indole-3-propanoic acid (MDL 29951), 7
      chloro-3-(cyclopropylcarbonyl)-4-hydroxy-2(1H)-quinoline (L701,252), 5,7
      dinitroquinaxoline-2,3-dione (MNQX) or 7-chlorothiokynurenic acid (7-CTK), or the
      PKC inhibitors, chelerythrine or GF109203X, the Sar9-SP-induced facilitation of
      ACBD-evoked activity was prevented, generally restoring activity to a level
      similar to that in the presence of ACBD alone, whilst an AMPA receptor
      antagonist, 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX) did not
      inhibit the facilitation. At the same ionophoretic currents these compounds had
      no effect on ACBD-evoked activity in the absence of Sar9-SP but were inhibitory
      at significantly greater currents. To further substantiate the importance of the
      GlyNMDA site in the interaction, the effects of NMDA receptor antagonists
      selective for alternative recognition sites on the NMDA receptor were
      investigated. MK-801, a non-competitive NMDA receptor antagonist and arcaine, a
      competitive inhibitor at the polyamine site, were applied to the facilitated
      activity seen in the presence of Sar9-SP and ACBD, and to ACBD-evoked activity
      alone. Unlike the GlyNMDA site antagonists and PKC inhibitors, these compounds
      reduced both facilitated and ACBD-evoked activity at similar currents.
      Furthermore, like the NK1 receptor agonist, a selective GlyNMDA site agonist 1
      aminocyclopropane carboxylic acid (ACPC) caused facilitation of ACBD-evoked
      activity which was also blocked by currents of L701,252 that did not alter
      activity evoked by ACBD alone. These data suggest that activation of the GlyNMDA
      site (perhaps as a consequence of glycine release or modification of its
      influence by intracellular signalling cascades) is an essential component of the
      means by which NK1 receptor activation results in facilitated responsiveness of
      dorsal horn neurons towards NMDA receptor agonists.

PMID- 9027385
TI  - The lateral and medial compartments of the olfactory tubercle and their relation
      to olfactory-related input as determined by artificial neural network.
AB  - The current literature indicates that olfactory bulbar input projects throughout
      layer IA of the entire olfactory tubercle, with apparently more fibres in the
      lateral part than in the medial part of the tubercle. In addition, olfactory
      cortical association fibers project to layers IB, II, and III in all regions of
      the tubercle. This study exploited the phenomenon of transsynaptic transfer of
      WGA-HRP after injection into the olfactory bulb or rats to explore the degree of
      olfactory-related input to the tubercle. A computerized image analysis system was
      employed to quantify the amount of tracer transferred to layer II neurons of the
      tubercle. Qualitative analysis of the data indicates that the lateral tubercle
      consists of areas that receive little olfactory-related input. Nonparametric
      statistical tests and a novel application of artificial neural networks indicate
      regionally heterogeneous labeling across the tubercle and broad connections
      between homologous regions of the bulb and tubercle. These results have
      implications for understanding how olfactory sensory information is integrated
      into limbic-motor circuits by the olfactory tubercle.

PMID- 9027386
TI  - Central integration of the Bezold-Jarish reflex in the cat.
AB  - The medullary structures involved in the central Bezold-Jarisch reflex pathway
      were studied by recording unit activity of sympatho-excitatory (SE) or inhibitory
      (SI) cardiovascular neurons in pentobarbital-anesthetized cats. The neurons were
      selected based upon their spontaneous activity and upon their sensitivity to
      baroreceptor reflex activation by L-phenylephrine. The Bezold-Jarisch reflex was
      induced by i.v. injection of chlorophenylbiguanide 10 micrograms/kg which
      produced a short-lasting decrease in blood pressure, heart rate and renal nerve
      activity. 76 neurons were studied. In 10 out of 12 SE neurons of the rostral
      ventrolateral medulla the activity was inhibited by chlorophenylbiguanide whereas
      in 10 out of 11 SI neurons and 6 out of 6 baroreflex-insensitive cells of the
      caudal ventrolateral medulla it was activated. The others cells were insensitive.
      Three types of neurons: excitatory, inhibitory or non-barosensitive, were
      recorded in the lateral tegmental field (27 cells) and the medullary raphe (20
      cells). These neurons were either activated, inhibited or insensitive to Bezold
      Jarisch reflex activation. Microinjection of the glutamate receptor antagonist
      kynurenic acid (2.5 nmol/site) or the GABAergic agonist muscimol (1 nmol/site)
      into the nucleus tractus solitarii abolished the effects of both L-phenylephrine
      and chlorophenyl-biguanide on heart rate and renal nerve activity. These results
      indicate that the cardiovascular neurons (sympatho-excitatory and sympatho
      inhibitory) located in the medullary areas, involved in cardiovascular and
      baroreflex mechanisms, are implicated in the central Bezold-Jarish reflex
      pathway.

PMID- 9027387
TI  - Delta and kappa opioid receptors in eyestalk ganglia of a crustacean.
AB  - Crustacean eyestalk ganglia are part of the protocerebrum and have been
      demonstrated to produce numerous neurohormones. 3H(2-D-Pen, 5-D-Pen)-enkephalin,
      3H-(-)-ethylketocyclazocine and 3H(D-Ala2-NMePhe-Glyol5)-enkephalin were used as
      ligands for opioid receptors on neuronal membrane preparations of eyestalk
      ganglia under consideration of their stereospecific binding properties. In
      context with saturation binding isotherms, association and dissociation plots, we
      demonstrate here two opioid receptors; a delta-type receptor with high affinity
      (Bmax 68.5 fmol/mg protein, Kd = 4.0 nM) and low affinity (Bmax 493 fmol/mg, Kd =
      83.6 nM) and a second receptor of kappa-type with Bmax of 3.1 pmol/mg protein and
      Kd = 68.6 nM.

PMID- 9027388
TI  - Decrease in highly polysialylated neuronal cell adhesion molecules and in spatial
      learning during ageing are not correlated.
AB  - Age-dependent spatial memory impairments have been related to a decline in
      hippocampal plasticity. Highly polysialylated neuronal cell adhesion molecules
      (PSA-NCAM) show a strong expression during adulthood within regions associated
      with neuroplastic events. Furthermore, NCAM molecules have been proposed to
      mediate neuronal plasticity during learning and memory. The aim of the present
      study was to examine the effect of ageing on the expression of PSA-NCAM within
      the hippocampus. To investigate whether age-dependent changes in expression of
      PSA-NCAM were accentuated in aged rats with learning impairment, animals were in
      a first step assessed for their cognitive abilities using a Morris water maze.
      Seven-month-old and 24-month-old-rats were tested for their performance in the
      Morris water maze. The animals were sacrificed and brain sections were processed
      for PSA-NCAM immunohistochemistry. Ageing was accompanied by an overall decrease
      in PSA-NCAM-immunoreactivity (-IR) within the forebrain, presenting a important
      decrease of the number of PSA-NCAM-IR perikarya within the hippocampus. These
      results were confirmed by Western blot analysis. No difference in PSA-NCAM
      immunoreactivity was observed in aged rats with or without spatial learning
      impairment. It is concluded that although changes in PSA-NCAM accompanied the
      decrease in cognitive abilities, our data did not evidence a causal relationship
      between these two parameters.

PMID- 9027389
TI  - Differential effects of SCH 23390 on the apomorphine subsensitivity in the
      substantia nigra and ventral tegmental area 1 day following withdrawal from
      continuous or intermittent cocaine pretreatment.
AB  - Using extracellular single-unit recordings in rats, the effects of chronic
      intermittent injections and continuous infusion of cocaine on single dopamine
      neurons were directly compared in the substantia nigra and ventral tegmental
      area. After 1-day withdrawal we determined: (1) the neuronal sensitivity to the
      mixed D1/D2 agonist apomorphine and (2) its modulation by the D1 antagonist SCH
      23390. The nigral dopamine neurons exhibited subsensitivity to the impulse
      inhibiting effects of apomorphine following both intermittent and continuous
      regimens. SCH 23390 selectively reversed the apomorphine subsensitivity in the
      intermittent group, while having minimal effects in the other group. Dopamine
      neurons in the ventral tegmental area, on the other hand, were sub- and
      normosensitive to apomorphine following intermittent and continuous dosing
      regimens, respectively. In contrast to the substantia nigra, SCH 23390 failed to
      alter the apomorphine sensitivity in either of the pretreatment groups. Possible
      mechanisms underlying these distinctive changes in the substantia nigra and
      ventral tegmental area following intermittent and continuous cocaine pretreatment
      regimens are discussed.

PMID- 9027390
TI  - Temperature and amiloride alter taste nerve responses to Na+, K+, and NH+4 salts
      in rats.
AB  - The effects of adaptation/stimulus temperature (25 degrees C vs. 35 degrees C) on
      taste nerve responses to salt stimulation and amiloride suppression were assessed
      in rats. We measured the integrated responses of the chorda tympani nerve to 500
      mM concentrations of NaCl, Na2SO4, sodium acetate (NaAc), KCl, K2SO4, potassium
      acetate (KAc), NH4Cl, (NH4)2SO4, and ammonium acetate (NH4Ac) mixed with or
      without 100 microM amiloride hydrochloride at 35 degrees C. Taste nerve responses
      to all Na+ and NH4+ salts, but not K/ salts, were significantly smaller at 25
      degrees C than at 35 degrees C. Amiloride significantly suppressed taste nerve
      responses to all salts (Na+ salts > K+ salts > NH4+ salts); amiloride suppression
      of Na+ and NH4+ salts was significantly greater at 25 degrees C than at 35
      degrees C. Benzamil-HCl, a more potent Na+ channel blocker compared to amiloride,
      strongly suppressed taste nerve responses to NaCl and KCl, but not to NH4Cl.
      Amiloride and benzamil suppression of NaCl responses were similar; however,
      amiloride suppressed KCl responses more than did benzamil. The results suggest
      that: (1) amiloride-sensitive Na+ channels are involved to varying degrees in the
      transduction of sodium and potassium salt taste, and (2) amiloride may inhibit
      membrane proteins other than passive Na+ channels during stimulation with
      potassium and ammonium salts.

PMID- 9027391
TI  - Forebrain endothelium expresses GLUT4, the insulin-responsive glucose
      transporter.
AB  - The presence of GLUT4, the insulin-responsive glucose transporter, in
      microvascular endothelium and the responsiveness of glucose transport at the
      blood-brain barrier to insulin have been matters of controversy. To address these
      issues, we examined GLUT4 mRNA and protein expression in isolated brain
      microvessels and in cultured calf vascular cells derived from brain microvessels
      and aorta. We report here that GLUT4 mRNA can be detected in rat forebrain and
      its microvasculature using high stringency hybridization of poly(A)+ RNA isolated
      from these sources. This mRNA is identical to that found in adipose cells from
      rat. Immunoblot analysis of isolate brain microvessels reveals that GLUT4 protein
      is also present. Peptide preadsorption studies and absence of our antibody
      reaction to human red cells suggest these findings are specific.
      Immunohistochemical staining of cultured calf vascular cells reveals that GLUT4
      is expressed in brain endothelial cells but not pericytes, nor in aortic
      endothelium or smooth muscle cells. The sensitivity of the methods required to
      detect GLUT4 in brain and comparison to its abundance in low density microsomes
      from rat adipose cells indicate that GLUT4 is expressed in relatively low
      abundance in brain microvascular endothelium. No significant differences are
      observed in steady state levels of GLUT4 mRNA in brain from streptozotocin
      diabetic compared to control rats. This last finding supports the concept of
      tissue-specific regulation of GLUT4. We conclude that brain microvascular
      endothelium specifically expressed GLUT4 while other vascular cells do not.

PMID- 9027392
TI  - Involvement of dopamine-dependent and -independent mechanisms in the rewarding
      effects mediated by delta opioid receptor subtypes in mice.
AB  - The rewarding effects of the delta 1 opioid receptor agonist [D-Pen2,
      Pen5]enkephalin (DPDPE) and the delta 2 opioid receptor agonist [D
      Ala2]deltorphin II (DELT) on the activity of mesolimbic and nigrostriatal
      dopamine (DA) neurons were examined in mice. Both DPDPE (15 nmol, i.c.v.) and
      DELT (5 nmol, i.c.v.) produced a significant place preference in mice. The DPDPE
      (15 mol, i.c.v.)-induced place preference was abolished by 7
      benzylidenenaltrexone (BNTX; 0.5 mg/kg, s.c.), a delta1 opioid receptor
      antagonist, but not by naltriben (NTB; 0.5 mg/kg, s.c.), a delta 2 opioid
      receptor antagonist. In contrast, the DELT (5 nmol, i.c.v.)-induced place
      preference was antagonized by NTB, but not BNTX. I.c.v.. injection of DPDPE, but
      not DELT, at a dose that produced a significant place preference produced a
      significant elevation of DA turnover in the mouse limbic forebrain, and this
      effect of DPDPE was antagonized by BNTX but not by NTB. In addition, i.c.v.
      injection of DPDPE or DELT not affect DA turnover in the mouse striatum. These
      results suggest that the rewarding effects produced by the activation of central
      delta 1, but not delta 2, opioid receptors may be caused through the enhancement
      of the mesolimbic DA neurotransmission, and confirm our previous hypothesis that
      the DA-dependent and -independent mechanisms may exist in the rewarding effects
      produced by the activation of central delta opioid receptor subtypes.

PMID- 9027393
TI  - Differential distribution of an endothelial barrier antigen between the pial and
      cortical microvessels of the rat.
AB  - An endothelial barrier antigen (EBA), reported to be a marker for endothelial
      cells (EC) displaying blood-brain barrier (BBB) characteristics, was probed with
      a monoclonal antibody in pial and cortical microvessels in rat brain. In contrast
      to the uniform labelling of EC in cortical vessels, pial microvessels showed a
      heterogeneity in EBA expression. Most pial vessels consisted of a mixture of EBA
      positive and EBA negative cells whereas a smaller number of vessels were either
      completely negative or uniformly positive. Significantly, in vessels showing
      incomplete expression it was typically EC furthest from the brain surface that
      did not express EBA. Although the function of EBA is unknown, the variable
      expression in pial microvascular EC may be related to their incomplete barrier
      characteristics.

PMID- 9027394
TI  - Preservation of dendrites with the presence of reorganized mossy fiber
      collaterals in hippocampal dentate granule cells in patients with temporal lobe
      epilepsy.
AB  - Dendritic morphology was studied in human hippocampal dentate granule cells
      (DGCs) by intracellularly-injecting biocytin in slice preparations that were
      obtained from temporal lobe epilepsy patients who underwent a surgical treatment
      for medically-intractable seizures. These DGCs had a fan-shaped dendritic domain
      of 54.1 degrees +/- 4.1 S.E.M. with 13.8 +/- 1.1 branch points and an estimated
      total dendritic length of 11535.6 microns +/- 3045.4. Dendritic spines were
      counted, and spine density was calculated to be 0.25 spines/microns +/- 0.16
      S.E.M.. However, when the cells were categorized into two groups based on the
      presence or absence of the aberrant mossy fiber collaterals, the number of
      dendritic branches was significantly lower and spine density was significantly
      higher in DGCs that had aberrant collaterals. In particular, in the proximal
      dendrite, the spine density was 5 times higher in DGCs whose own mossy fibers
      were reorganized sending aberrant collaterals to this dendritic region (0.750
      spines/microns +/- 0.203 S.E.M.: P < 0.01) than the DGCs without such collaterals
      (0.082 spines/microns +/- p.021 S.E.M.). These results suggest that the axonal
      reorganization may have an effect on the morphology of DGC dendrites directly or
      indirectly in such a way that dendritic structure and spines could be protected
      from seizure-induced excitotoxic cell damage.

PMID- 9027395
TI  - Removal after addition of NO-generating agents and 8-bromo-cyclic GMP causes
      morphological change of cultured cerebellar astrocytes: a new mode of NO action.
AB  - The effect of nitric oxide (NO) on cell morphology was investigated in primary
      cultures of cerebellar astrocytes. Although the addition of NO donors to the
      culture medium did not change glial morphology, their removal did, with the form
      of astrocytes changing from flat to process bearing. This 'removal effect' may be
      a new mode of NO action.

PMID- 9027396
TI  - Modulation of a competitive N-methyl-D-aspartate receptor antagonist binding by
      zinc oxide.
AB  - Zinc through a zinc binding site is known to modulate the binding of agonists at
      the NMDA receptor. In the present study, the ability of zinc oxide to alter the
      specific binding of [3H]CGP-39653, a competitive NMDA receptor antagonist, was
      determined in homogenate of rat brain tissue. Analysis of saturation experiments
      indicated that zinc oxide significantly increased the Kd without changing Bmax of
      [3H]CGP-39653 binding. Furthermore, the effect of ZnO on glutamate and glycine
      displacement of [3H]CGP-39653 binding was determined. The results of the [3H]CGP
      39653 displacement study indicated that ZnO decreases the glutamate and glycine
      displacement of [3H]CGP-39653 binding.

PMID- 9027397
TI  - Serotonergic modulation of 3,4-methylenedioxymethamphetamine (MDMA)-elicited
      reduction of response rate but not rewarding threshold in accumbal self
      stimulation.
AB  - In a fixed interval 5-s rate-frequency function paradigm with rats, 3,4
      methylenedioxymethamphetamine (MDMA; 0.5, 2 and 4 mg/kg) dose-dependently
      decreased response rate for nucleus accumbens self-stimulation while both D
      amphetamine (0.3 and 1 mg/kg) and cocaine (5 and 15 mg /kg) increased response
      rates. The highest doses of MDMA caused a cessation of responding in many of the
      rats tested, but in those rats that continued to respond a significant reduction
      in frequency threshold for self-stimulation was seen. Cocaine and amphetamine
      dose-dependently reduced frequency threshold in all rats tested. The non-specific
      serotonin antagonist, methysergide (5 mg/kg), reversed the inhibitory effects of
      MDMA on response rates and caused all rats to respond following MDMA (4 mg/kg).
      Methysergide did not affect MDMA's threshold-lowering properties and when
      administered alone methysergide had not effect on self-stimulation. These results
      suggest serotonergic involvement in the performance but not reinforcement
      modulating effect of MDMA in the self-stimulation paradigm.

PMID- 9027398
TI  - Purkinje cell loss in heterozygous staggerer mutant mice during aging.
AB  - The cerebellum on the heterozygous (+/sg) staggerer mutant mouse has recently
      been proposed as a model system in which to study the genetic contribution to the
      normal process of central nervous system aging since there is significant loss of
      neurons from 3 to 12 months of age (Shojaeian-Zanjani, H., Mariani, J., Delhaye
      Bouchaud, N., and Herrup, K. (1992) Dev. Brain Res., 67, 153-160). In the current
      study we extend our analysis of the changes in Purkinje cell numbers up to 24
      months of age in +/sg and C57BL/6J wild-type mice. At 13 and 18 months, while
      wild-type Purkinje cell numbers remain unchanged, there is a 22-26% loss in the
      number of Purkinje cells in +/sg after which no further cell loss is observed.
      Between 18 and 24 months, however, a 22% loss of Purkinje cell occurs in +/+
      animals, with the result that by 2 years of age, the size of the Purkinje cell
      population is again similar in both genotypes. Analysis of the cell loss in both
      the mediolateral and the anteroposterior dimensions, as well as the
      immunostaining of Purkinje cells in frontal sections, reveal no obvious regional
      variation in the Purkinje cell loss. These results suggest that in +/sg, a
      precocious process of aging affects the size of the Purkinje cell population.

PMID- 9027399
TI  - Survival of Cajal-Retzius cells after cortical lesions in newborn mice: a
      possible role for Cajal-Retzius cells in brain repair.
AB  - Transient Cajal-Retzius (CR) cells in layer I of the mammalian cerebral cortex
      are the first postmitotic neurons and they are believed to play a role in
      neuronal migration and lamination during cortical development. Freezing insults
      to the cortex of newborn mice produce cortical malformations similar to those
      observed in human brain disorders. Here we have used calretinin immunostaining to
      investigate the response of CR cells to freezing lesions of the cortical surface.
      Shortly after injury, CR cells disappeared from the lesioned zone. Moreover, CR
      cells located near the lesioned area adopted extremely fusiform shapes. At later
      postnatal stages (P12), CR cells were still abundant in layer I of the lesioned
      zone, in contrast to their almost complete loss in control animals. These results
      show that CR cells survive for longer developmental periods following cortical
      injury. Furthermore, the initial loss and later re-appearance of CR cells suggest
      that these neurons might migrate tangentially from the cortical areas surrounding
      the lesioned zone. These findings imply a role for CR cells in brain repair after
      cortical injury during development.

PMID- 9027400
TI  - Degeneration of Cajal-Retzius cells in the developing cerebral cortex of the
      mouse after ablation of meningeal cells by 6-hydroxydopamine.
AB  - In the central nervous system, the neurotoxic drug 6-hydroxydopamine (6-OHDA)
      selectively deletes central catecholaminergic neurons and meningeal cells.
      Meningeal cells are known to contribute to brain development and their specific
      degeneration leads to disorganized neuronal positioning. We have analyzed whether
      a particular population of cortical pioneer neurons, the Cajal-Retzius (CR)
      cells, which lie just below meningeal cells, is also affected by 6-OHDA
      treatment. We show that application of 6-OHDA to the cortical surface leads to a
      rapid degeneration of CR cells, without affecting other cortical neurons. The
      ablation of CR cells was prevented by normetanephrine, which blocks the 6-OHDA
      uptake into meningeal cells. These results indicate that the disappearance of CR
      cells after 6-OHDA treatment may be a result of the ablation of the meningeal
      cells and suggest a trophic dependence of CR cells upon meningeal cells.

PMID- 9027401
TI  - Cocultured, but not isolated, cortical explants display normal dendritic
      development: a long-term quantitative study.
AB  - Dendritic growth has been studied in long-term organotypic neonatal rat occipital
      neocortex grown either apart as isolated explants or in tandem as cocultures.
      Quantitative light microscopic measurement of dendritic and axonal branching
      patterns within the cortical slice was accomplished using rapid Golgi stained
      materials. In both isolates and cocultures the overall cellular organization of
      the slice was maintained over 4 weeks in vitro with morphologically
      distinguishable pyramidal and nonpyramidal neurons located within the same layers
      and with the same orientations as observed in situ. Long-term increases in the
      total length of basal dendrites, apical dendrite and axons were observed only in
      cocultures and were similar to growth patterns reported for in situ materials.
      Dendritic growth was mainly due to elongation of terminal dendritic segments.
      Surprisingly, isolated explants showed no long-term increases in total (basal)
      dendrites, apical dendrites or axons with time in vitro. A transient decrease in
      the number of basal dendritic segments and increase in terminal segment lengths
      at the end of the first week in vitro, however, was observed in nonpyramidal
      neurons. It is hypothesized that (i) afferent inputs and/or efferent targets
      develop only in cocultures and provide a crucial conditions for the continued
      growth of dendritic/axonal arborization for neocortical neurons in vitro, (ii)
      intrinsic interconnectivity within isolated explants is not sufficient to
      maintain long-term growth of neuritic arbors, and (iii) remodelling of dendritic
      arbors within isolated explants occurs at the same time as these explants are
      showing noticeable increases in the level of spontaneous bioelectric activity,
      which suggests that dendritic growth and network formation may be function
      dependent.

PMID- 9027402
TI  - Glycine-activated whole cell and single channel currents in rat cerebellar
      granule cells in culture.
AB  - The patch clamp technique was used to study whole cell and single channel
      currents evoked by glycine in cerebellar granule cells in culture. Whole cell
      concentration response curve gave a Kd value for glycine of 73 microM and a Hill
      slope of 1.58. Glycine-activated currents reversed close to the predicted Cl-
      equilibrium potential. The responses to glycine were antagonized by strychnine
      and picrotoxin with an IC50 of 58 nM and 172 microM, respectively. Furthermore,
      glycine-evoked currents were potentiated by zinc in a dose-dependent way. In
      outside-out membrane patches, glycine opened channels with conductances of 32,
      52, 84 and 96 pS. The most frequently occurring was the 52 pS channel. The single
      channel current/voltage relationship was linear in the potential range between 
      60 and 60 mV. The 52, 84 and 96 pS channels exhibited prolonged openings whereas
      the 32 pS was characterized by fast (< 10 ms) openings. Open and closed time
      histograms of the 52 pS channel could be fitted with the sum of two or three
      exponentials, respectively, whereas burst duration histograms could be fitted
      with the sum of two exponentials. Glycine current density change drastically
      during days in culture, the maximal expression being between day 4 and 7,
      suggesting that the expression of glycine receptor channels is developmentally
      regulated.

PMID- 9027403
TI  - Postnatal changes in the laminar and subcellular distribution of NMDA-R1 subunits
      in the cat visual cortex as revealed by immuno-electron microscopy.
AB  - Although it is recognized that nearly all synapses in the cerebral cortex form
      postnatally, little is known about the emergence of molecules necessary to render
      these synapses functional. This study visualized the emergence of synaptically
      localized NMDA receptors by immuno-electron microscopic labeling of the
      receptor's obligatory subunit, NMDA-R1, in the developing cat visual cortex.
      Prior to eye-opening (postnatal day 2-10), NMDA-R1 immunoreactivity is already
      present within dendritic and growth cones, even though these profiles are devoid
      of synaptic specializations. This indicates that synthesis and incorporation of
      NMDA-R1 into plasma membranes are independent of form vision. During the next 2-3
      weeks, i.e., preceding the onset of the critical period for ocular dominance
      plasticity (around the fourth week), NMDA-R1 immunoreactivity changes from a
      diffuse distribution within dendrites to a more discrete aggregation over
      postsynaptic densities of axo-spinous junctions. Such clustering of NMDA-R1 at
      synapses may be a prerequisite for stabilization and strengthening of synapses
      activated by visual stimulation during the critical period. Furthermore, only
      during the first several weeks, intensely NMDA-R1-immunoreactive neurons are
      present in the infragranular layers and the white matter. Enrichment of NMDA-R1
      in the deep-layer neurons may reflect the neurons' supportive role in the
      development of cortical circuitry, serving as transient synaptic targets for
      geniculate and cortico-cortical afferents while these afferents 'wait' in the
      infragranular for their ultimate, life-long target neurons to become receptive in
      the upper layers.

PMID- 9027404
TI  - GABA metabolism during status epilepticus in the developing rat brain.
AB  - The rate of synthesis of GABA, the major inhibitory neurotransmitter, was
      determined in parietal cortex and hippocampus during SE induced by systemic
      administration of lithium (3 mEq/kg) followed 20 h later by pilocarpine (100
      mg/kg) in 1-4-week-old rats. Our results show that the immature hippocampus is
      better capable of maintaining GABA synthesis in the face of SE at the earliest
      stages of development studied (74.1% of basal in 1-week-old) and that development
      results in a progressive decline in the ability to maintain GABA synthesis in the
      face of SE (44.1% of basal by 4 weeks) that may parallel the ontogeny of self
      sustaining seizures. Our data describe an aspect of developmental GABA
      neurochemistry which may in part explain the relative resistance of the immature
      hippocampus to seizure spread and of certain types of seizure-induced damage.

PMID- 9027406
TI  - Androgens stimulate the morphological maturation of embryonic hypothalamic
      aromatase-immunoreactive neurons in the mouse.
AB  - Gonadal steroids play an important role as developmental factors for the rodent
      brain and are implicated in the sexual differentiation of neural structures.
      Estrogens have been linked to survival and plasticity of central neurons, thereby
      regulating the development of hypothalamic and limbic structures associated with
      reproductive functions. Besides estrogens, androgens also contribute actively to
      CNS maturation. We have shown recently that androgens stimulate the receptor
      mediated functional differentiation of cultured hypothalamic aromatase
      immunoreactive (Arom-IR) neurons by stimulating the expression of Arom, the key
      enzyme in estrogen formation. In the present study, we investigated whether
      androgens are capable of influencing morphological differentiation of
      hypothalamic Arom-IR neurons. Androgen treatment, unlike estrogen, stimulated the
      morphological differentiation of cultured embryonic hypothalamic Arom-IR cells by
      increasing neurite outgrowth and branching, soma size, and the number of stem
      processes. This effect was brain region- and transmitter phenotype-specific;
      neither cortical Arom-IR neurons nor hypothalamic GABAergic neurons responded to
      androgens. Moreover, morphogenetic effects depended on androgen receptor (AR)
      activation, since morphological changes were completely inhibited by flutamide.
      Double-labeling of hypothalamic Arom-IR neurons revealed a considerable number of
      cells coexpressing AR, whereas cortical Arom-IR cells did not label for AR. Our
      data demonstrate that androgens function as morphogenetic signals for developing
      hypothalamic Arom-IR cells, thus being potentially effective in influencing
      plasticity and synaptic connectivity of hypothalamic Arom-systems.

PMID- 9027405
TI  - Early molecular specification in the hippocampal rudiment: isolation of genes
      expressed in a region-specific manner in the embryonic telencephalon.
AB  - During development, the structure of the telencephalon is dramatically
      transformed by region-specific proliferation and differentiation of
      neuroepithelial cells. To understand mechanisms of morphogenesis in the
      telencephalon, a search was made for genes expressed in a region-specific manner
      in the dorsal telencephalon of embryonic rats. Dorso-lateral and dorso-medial
      portions of the telencephalon were taken from rat fetuses on embryonic day (E)
      13. Genes expressed in each portion were compared by a modified differential
      display method. Among more than 4000 cDNA fragments, four fragments termed M1,
      M1', M2 and M3 were found only after amplification of cDNAs derived from the
      dorso-medial portion of the telencephalon. Nucleotide sequence and Northern blot
      analyses showed that M1 and M1' were identical and that M2 and M3 were related
      genes. In situ hybridization revealed that M1 was expressed in a restricted
      portion of the hippocampal rudiment with a sharp boundary. M2 and M3 were
      expressed in the hippocampal rudiment with a more diffuse boundary than that of
      M1. Expression of M2 and M3 was also found in the most anterior part of the
      medial diencephalon with a caudal extension along the dorsal midline. These
      results suggest that at least two types of molecular specification occur in the
      dorso-medial telencephalon, contributing to the construction of the hippocampal
      elements during early stages of development.

PMID- 9027407
TI  - Postnatal development of synaptic plasticity in the CA3 hippocampal region of
      control and lead-exposed Wistar rats.
AB  - The object of this study was to compare the postnatal development of mossy fiber
      potentiation (MFP) and paired-pulse facilitation in the CA3 region of control and
      led-exposed rats. The postnatal development of MFP was not influenced by the
      chronic pre- and postnatal lead exposure nor did we find a statistically
      significant impairment of MFP in region CA3 following lead exposure in the four
      age groups studied. In contrast to the adult animals, in the three immature
      groups of the control as well as the lead-exposed animals MFP was preceded by a
      posttetanic depression after which MFP developed slowly. The results of the
      paired-pulse procedure depended both on the age and on the interstimulus interval
      (ISI) in control and lead-exposed animals. The differences between control and
      lead-exposed rats were statistically significant only in the adult animals at an
      ISI of 10 ms. In this case paired-pulse stimulation resulted in an increase of
      the second evoked response relative to the first response in the lead-exposed
      animals while the same procedure decreased the second evoked response in the
      control animals. It is concluded that although low lead exposure had no effect on
      the expression of MFP in hippocampal CA3 region, inhibitory mechanisms as
      revealed by paired-pulse stimulation are impaired by lead in adult rats.

PMID- 9027408
TI  - Carbonic anhydrase II and carbonic anhydrase-related protein in the cerebellar
      cortex of normal and lurcher mice.
AB  - The developmental profiles of carbonic anhydrase II (CA-II) and a carbonic
      anhydrase related protein (CARP) were studied in rat and mouse cerebella. Enzyme
      histochemistry, immunohistochemistry, in situ hybridisation and Western blotting
      were used to study the synthesis and expression of these enzymes in cerebellar
      sections from age matched control, CA-II deficient and lurcher mice, the latter
      being characterised by Purkinje cell degeneration. Both CA-II and CARP were first
      found to be expressed in the Purkinje cells in the 9 day old mouse, and the
      immunoreactivity of both peptides increased with time. Immunohistochemistry
      showed more intense staining of CARP than of CA-II in Purkinje cells throughout
      the developmental profile of the mouse, and this was mirrored by the mRNA levels
      determined by in situ hybridisation. Immunohistochemistry of CA-II and CARP also
      demonstrated the progressive dendritic growth of the mouse and rat Purkinje
      cells. CA-II and CARP immunoreactivity ceased by the end of cerebellar
      maturation. The onset of Purkinje cell degeneration was detected at day 10 in the
      lurcher mouse, with concomitant marked decrease in CA-II level: however CARP
      expression was found to be unchanged. By postnatal day 16 neither CA-II mRNA,
      protein, nor activity was detectable in contrast to CARP which remained at a
      decreased level unit the Purkinje cells population had completely degenerated.
      Our findings suggest a role of CA-II in the degenerative processes of the lurcher
      Purkinje cells, with CARP playing an important role in the development and
      maturation of the cerebellar cortex.

PMID- 9027409
TI  - Localisation of insulin-like growth factor-I (IGF-I) immunoreactivity in the
      olivocerebellar system of developing and adult rats.
AB  - The molecular mechanisms which underlie the development of the olivocerebellar
      topography are not fully understood. Insulin-like growth factor-I (IGF-I) is a
      growth factor known to play important roles in neural development and it has been
      identified within the cerebellum and the inferior olive. To assess the
      contribution of IGF-I to the development of climbing fibre topography, the
      distribution of IGF-I-like immunoreactivity (IGF-I IR) was identified in the
      cerebellar cortex and inferior olive of rats, 0, 3, 5, 7, 10, 15, 21, 28 and 90
      days old. In the cerebellar cortex, IGF-I IR was localised solely to Purkinje
      cells and its distribution was spatially and temporally regulated in a manner
      which coincides with climbing fibre development. At birth, weak IGF-I IR was
      detected in a few Purkinje cells in the ventral vermis. More Purkinje cells
      became positive until at postnatal day 7(P7) all Purkinje cells displayed IGF-I
      IR. Subsequently, a subpopulation of Purkinje cells lost their reactivity for IGF
      I to leave IGF-I-positive cells organised into sagittal bands by P15. IGF-I IR
      was also seen in all subdivisions of the inferior olive between birth and P10 in
      a distribution which paralleled the maturation of the inferior olive. The
      Purkinje cell and inferior olivary IGF-I IR parallels climbing fibre development
      and thus the results of this study support the hypothesis that IGF-I is involved
      in the development of climbing fibre topography.

PMID- 9027410
TI  - Amphetamine-induced preprodynorphin mRNA expression and kappa-opioid receptor
      binding in basal ganglia of adult rats after prenatal exposure to diazepam.
AB  - In order to obtain information on the functional state of basal ganglia following
      prenatal benzodiazepine exposure, preprodynorphin mRNA expression and kappa
      opioid receptors were studied in offspring of timed-pregnant Long Evans rats
      treated with diazepam (1.25 mg/kg/day) on gestational days 14 to 20.
      Preprodynorphin mRNA was localised by in situ hybridization using a 33P-labeled
      oligonucleotide. Relative optical density (ROD) was quantified by image analysis
      in four quadrants of caudate putamen, in nucleus accumbens and olfactory tubercle
      of adult male rats. Six hours after functional challenge by injection of D
      amphetamine (8 mg/kg s.c.), prenatally vehicle-exposed rats exhibited increased
      preprodynorphin mRNA (ROD) levels in caudate putamen (dorsolateral 187%,
      dorsomedial 150%, ventrolateral 153%, ventromedial 140% of control), nucleus
      accumbens (142%) and olfactory tubercle (213%). Prenatal diazepam exposure
      attenuated the effect of amphetamine in all regions; statistically significant
      differences between ROD levels of prenatally vehicle/adult amphetamine-treated
      and prenatally diazepam/adult amphetamine-treated groups were seen in
      ventrolateral caudate putamen, nucleus accumbens and olfactory tubercle. Baseline
      levels and topographical distribution of preprodynorphin mRNA remained unchanged.
      kappa-opioid receptor binding was analyzed in membrane from nucleus accumbens +
      olfactory tubercle, caudate putamen, and midbrain of male and female offspring
      using [3h]U69593. Bmax was reduced in nucleus accumbens + olfactory tubercle, but
      not in caudate putamen or midbrain of adult, prenatally diazepam-exposed male
      offspring, This effect was not yet seen at earlier postnatal stages (14 and 28
      days), and was also absent in females. These data indicate that prenatal exposure
      to diazepam results in a delayed change in the functional state of dynorphin
      containing neurons in several parts of the basal ganglia of adult male offspring.
      The decreased responsiveness to enhanced dopaminergic transmissions may impair
      the function of basal ganglia circuitry.

PMID- 9027411
TI  - Expression of alpha 7 neuronal nicotinic receptors during postnatal development
      of the rate cerebellum.
AB  - Several lines of evidence suggest that alpha-bungarotoxin-sensitive neuronal
      nicotinic acetylcholine receptors may play a developmental role by modulating
      plasticity in neuronal circuits. The alpha 7 subunit, a main component of these
      receptors, is expressed in most regions of the brain, including the cerebellum,
      where it is present almost exclusively in Purkinje cells and deep cerebellar
      nuclei. Purkinje cells constitute the only efferent pathway of the cerebellum and
      their development involves complex interactions, which have been extensively
      studied. They therefore provide a potentially useful model for analysis of
      development plasticity which could be influenced by alpha 7 neuronal nicotinic
      receptors. In the present study a previously characterized monoclonal antibody
      (mAb 307) has been used to determine the temporal pattern of expression of the
      alpha 7 subunit in the developing rat cerebellum. No detectable alpha 7
      immunoreactivity is found between P0 and P2. Between P3 and P5, however, the
      Purkinje cell layer shows moderate immunolabeling. alpha 7 expression in this
      layer increases rapidly between P8 and P15. This increase in alpha 7 staining,
      which overlaps in time with important developmental and synaptogenic events, is
      not uniform throughout the cerebellar cortex. Thus, between P3 and P5 all
      Purkinje cells are weakly labeled, while at later stages (P8-P15) immunolabeling
      becomes more intense, but at the same time, disappears from Purkinje cells in
      rostral lobules. In addition, a very well defined pattern for discontinuous or
      columnar labeling is detected in regions of the Purkinje cell layer where alpha 7
      subunits were being expressed. Finally, at P20, alpha 7 subunit labeling is found
      again in all Purkinje cells, although with lower intensity. These results suggest
      that alpha 7 receptor expression is developmentally regulated, with a time course
      that parallels the final differentiation of Purkinje cells. In addition, the
      heterogeneous spatial distribution of alpha 7-containing nicotinic receptors
      indicates that, during cerebellar maturation, these cells may receive different
      signals that modulate receptor gene expression in a very specific way.

PMID- 9027412
TI  - Control of endogenous norepinephrine release in the hypothalamus of male rats
      changes over adolescent development.
AB  - In order to evaluate mechanisms that could contribute to the effect of adolescent
      development on the in vivo utilization of norepinephrine (NE) in the
      hypothalamus, the depolarized release of endogenous norepinephrine (using 50 mM
      potassium) was measured in vitro in hypothalamic explants from male rats over
      late juvenile (28 days) to young adult (70 days) ages. Depolarized release,
      expressed as a percent of the total endogenous pool, was significantly greater in
      juveniles than in either adolescents (42 days) or young adults. Incubation in the
      presence of idazoxan, an alpha 2-adrenoceptor antagonists, increased the
      depolarized fractional NE release in adolescent and young adult rats; however,
      the same drug decreased depolarized release in juveniles. Inhibition of
      norepinephrine reuptake by incubation in the presence of nisoxetine (1 microM)
      significantly increased depolarized release (fractional and absolute) in young
      adults only. A higher concentration of nisoxetine (5 microM) significantly
      increased depolarized release in juveniles, but significantly reduced release in
      adults. Nisoxetine did not influence release in adolescents at either
      concentration. The possibilities that adolescents development brings about a
      change in alpha 2-adrenoceptor subtype and that juveniles may have a greater NE
      reuptake capacity than adults are discussed. Hypothalamic NE projections are
      important to several regulatory functions, and changes that take place in this
      system over adolescence may be important for the emergence of adult-typical
      responses as well as render adolescents vulnerable to specific dysfunctions.

PMID- 9027413
TI  - Antinociceptive effects of intrathecally administered 2-methylserotonin in
      developing rats.
AB  - The present study examined developmental patterns of antinociception mediated by
      the spinal 5-HT3 receptor system in the neonatal rat. Intrathecally administered
      2-methylserotonin (25-100 micrograms) first produced antinociception against
      formalin-induced acute inflammatory pain at 10 days postnatally, with effect only
      at the peak dose (100 micrograms). Intrathecal 2-methylserotonin produced dose
      dependent antinociception at 14 and 28 days of age that was attenuated by i.t.
      pretreatment with the 5-HT3 receptor antagonist MDL-72222 (10 micrograms).

PMID- 9027414
TI  - Neonatal caffeine alters passive avoidance retention in rats in an age- and
      gender-related manner.
AB  - Chronic administration of an adenosine receptor antagonist disturbs spatial
      learning and memory in adult mice and neonatal caffeine exposure results in long
      term behavioral and biochemical sequelae in mice and rats. We thus postulated
      that early treatment with caffeine would have latent effects on learning and
      memory as measured in a passive avoidance paradigm. Rats were not handled or
      received caffeine (15-20 mg/kg/day) by gavage over postnatal days 2-6. At 28 or
      70-90 days of age, rats were trained to avoid an electrified grid and tested for
      retention 24 h, 72 h, and 7 days later. At 28 days, caffeine-exposed rats
      required more trials to meet criterion than did control rats, regardless of
      gender. There was minimal effect on retention of either neonatal treatment or
      gender at this age. At 70-90 days, there was no effect of either gender or
      treatment on learning; however, there was a significant effect of gender (P <
      0.05) on retention at 24 h that was more pronounced in neonatally caffeine
      treated rats (P < 0.01). At 72 h, the effect of caffeine on retention differed
      between male and female rats. Neonatal caffeine exposure significantly improved
      retention in females (P < 0.01) and significantly decreased retention in males (P
      < 0.05). Thus, caffeine exposure limited to the first week of life resulted in
      alterations in passive avoidance retention that became apparent over pubertal
      development. These changes were a function of the gender of the animal.

PMID- 9027422
TI  - Cytotoxicity of bilirubin for human fibroblasts and rat astrocytes in culture.
      Effect of the ratio of bilirubin to serum albumin.
AB  - The sensitivity of rat brain astrocytes and human fibroblasts in culture to
      unconjugated bilirubin was investigated. Medium containing 6 mumol/1 bilirubin
      and increasing concentrations of human serum albumin giving ratios of 0.5-1.5
      that resulted in an increase of the free bilirubin concentrations. The LDH
      activity in the culture medium was an index of cytolysis and the MTT assay was
      used as an index of mitochondrial impairment. The ratios producing half-maximum
      cell lysis after 24, 48, and 72 h, were 1.1, 0.9 and 0.85, for astrocytes, and
      1.2, 0.75 and 0.75, for fibroblasts. Mitochondrial activity decreased after 24 h
      for ratio = 0.7 and partly recovered at 48 h. Mitochondrial activity was more
      impaired in fibroblasts than in astrocytes above ratio = 0.7. The cytotoxic
      effects were linked to the free bilirubin concentration. We conclude that
      astrocytes are less sensitive to bilirubin cytotoxic effects than are
      fibroblasts.

PMID- 9027421
TI  - Antibodies to Tamm-Horsfall protein in patients treated with extracorporeal shock
      wave lithotripsy (ESWL).
AB  - The aim of this study was to determine antibodies to Tamm-Horsfall protein in
      patients with nephrolithiasis treated with extracorporeal shock wave lithotripsy
      (ESWL). The values of antibodies to Tamm-Horsfall protein were determined by
      direct enzyme immunoassay. No statistically significant differences (P > 0.05)
      were observed for the IgG and IgM classes of antibodies between the groups of
      healthy subjects and patients with nephrolithiasis before, and 30 and 60 days
      after ESWL. The values of IgA class determined 30 days after treatment were
      significantly higher (P < 0.05) in patients, which could be due to the
      stimulation of the immune system. The highest values of antibodies to Tamm
      Horsfall protein were obtained in both groups in the test with secondary
      antibodies directed toward IgM class, implicated at the presence of cross
      reactive antibodies. Determination of antibodies to THP subunits isolated form
      urine of patients with nephrolithiasis should be performed.

PMID- 9027423
TI  - Serum free 3,5,3'-triiodothyronine (T3) in non-thyroidal somatic illness, as
      measured by ultrafiltration and immunoextraction.
AB  - Serum free 3,5,3'-triidothyronine (T3) levels are regularly reported reduced in
      patients with non-thyroidal, somatic illnesses (NTI). However most free T3 assays
      have serious methodologically shortcoming. From a theoretical point of view,
      ultrafiltration may be the most reliable technique at present, and we have
      previously reported unaltered serum free T3 levels in NTI. A newly commercialized
      assay suitable for routine use (Amerlite MAB free T3) has demonstrated promising
      results in NTI sera, and we thus compared these two methods in a large group of
      NTI patients not treated with glucocorticoids or dopamine (n = 120), as well as
      in 66 healthy controls and 8 patients on prolonged dopamine infusion. In both
      assays free T3 levels were unaltered in NTI (NTI versus controls (mean), Amerlite
      MAB free T3: 5.47 versus 5.32 pmol/l; ultrafiltration free T3; 6.99 versus 7.60
      pmol/l). Free T3 levels outside normal range were found in 14% using the Amerlite
      MAB free T3 assay and 2% using the ultrafiltration assay. The two methods
      correlated in all subjects (n = 194) (r = 0.32 (P < 0.001) as well as in NTI
      patients (r = 0.34 (P < 0.001). No correlations to serum T4 levels were found,
      and patients with serum T4 levels below or above 70 nmol/l, had similar free T3
      concentrations in both assays. Patients on dopamine infusion had reduced serum
      free T3 levels (both assays), but the values were still within the normal range.
      CONCLUSION: Serum free T3 levels were unaltered in NTI patients using both
      assays, and the Amerlite MAB free T3 assays seems useable during diagnostic work
      up for possible thyroid disease in hospitalized patients with other somatic
      illnesses, despite the fact that this assay has some shortcomings, which are an
      integral part of all immunoextraction assays.

PMID- 9027424
TI  - Significant reduction of the bias among commercial immunoassays for
      lipoprotein(a) after use of a uniform calibrator.
AB  - Despite the increasing interest in the measurements of lipoprotein(a) (Lp(a) in
      serum or plasma, at present there is no effective standardization for Lp(a)
      assays; the main problems to solve are represented either by the lack of a
      suitable primary standard or by the absence of a reliable and widely available
      reference method. A first step is hence the uniformity of calibration of
      different immunoassays. We calibrated three commercial immunoassays for Lp(a)
      (enzyme linked immunosorbent assay (ELISA), latex-enhanced immunonephelometric
      assay (LINA), and immunonephelometric assay (INA) with either proprietary
      standards or purified Lp(a) material obtained with a rapid and simple procedure.
      Final results of purified Lp(a) calibration were reported in terms of protein
      Lp(a) mass whereas we were able to quantify the exact protein concentration of
      our purified lipoprotein. The uniformity of the calibration of the different
      assays led to a significant improvement of regression slopes (from 1.88 to 0.90
      ELISA vs. LINA, from 1.45 to 0.95 ELISA vs. INA and from 1.27 to 0.96 INA vs.
      LINA) and correlation coefficients (from 0.990 to 0.994 ELISA vs. LINA, from
      0.987 to 0.990 ELISA vs. INA and from 0.985 to 0.987 INA vs. LINA). Furthermore,
      the significant differences among Lp(a) values obtained after calibration with
      proprietary standards were minimized, becoming non-significant in two out of
      three cases. In conclusion, we demonstrated that a better agreement of Lp(a)
      values obtained with different commercial assays could be simply reached by
      uniformity of calibration and by employing standards with values accurately
      measured.

PMID- 9027425
TI  - A simple near-patient test for nicotine and its metabolites in urine to assess
      smoking habit.
AB  - We describe a disposable, near-patient urine test to monitor cigarette smoking. A
      plastic device contains the sealed dried reagents to measure nicotine and its
      metabolites, by a colorimetric assay. The device can be used to give a
      qualitative assessment of tobacco consumption, simply by observing a colour
      change. Alternatively, the test can be quantified by measuring the light
      absorbance with a simple colorimeter, and a concentration of nicotinic
      metabolites obtained with reference to a cotinine standard. A correction factor
      for the concentration of the urine sample, based on light absorbance, allows the
      result to be expressed as a ratio to urine concentration. This method correlates
      with reported daily cigarette consumption (r = 0.69, p < 0.0001) and compares
      favourably with cotinine, as measured by gas chromatography (r = 0.89, p <
      0.0001). The method provides a simple-to-use, inexpensive way to monitoring
      tobacco consumption in extralaboratory situations.

PMID- 9027426
TI  - Osteocalcin detection in aging serum and whole blood: stability of different
      osteocalcin fractions.
AB  - Human serum osteocalcin is a well known bone formation marker. On the basis of
      their different affinities for hydroxyapatite, the total immunoreactive
      osteocalcin may be separated into two fractions. Six commercial test kits for
      osteocalcin were compared. All kits reacted with both osteocalcin fractions but
      the absolute amounts found in the same serum samples differed widely. During
      serum storage at room temperature, there was no significant loss of osteocalcin
      during the first 6 h. After longer storage periods, the recorded decrease of
      osteocalcin depended on the system used: with two kits, over 80% of the original
      immunoreactive antigen was left after 9 days. It is considered that the different
      osteocalcin fractions may become useful as markers for different metabolic bone
      processes. A more precise definition of the various circulating osteocalcin
      fractions, and the development of separate tests for each fraction, are
      requirements for the optimal use of osteocalcin as a diagnostic tool for
      metabolic bone disorders.

PMID- 9027427
TI  - The relationship between hyaluronidase activity and hyaluronic acid concentration
      in sera from normal controls and from patients with disseminated neoplasm.
AB  - Serum hyaluronidase activity (HAE) and hyaluronic acid (HA) concentration were
      measured in sera from patients with disseminated neoplasm and compared to those
      of normal controls. The serum HAE activity in disseminated neoplasm (mean, 12.6
      mumol N-acetylglucosamine (NAG)/min/1; range, 5.2-24.7 mumol NAG/min/1) was
      significantly lower (t = 6.7, p < 0.001) than in normal controls (mean, 17.1
      mumol NAG/min/1; range, 11.5-27.0 mumol NAG/min/1). The serum HA concentration in
      patients with disseminated neoplasm (mean, 8199.7 micrograms/l; range, 42.0
      496,000 micrograms/l) was significantly higher (t = 2.63, 0.01 > p> 0.001) than
      in normal age-matched controls (mean, 55.6 micrograms/l; range, 10.0-348.0
      micrograms/l). A negative correlation was found between the serum HAE activity
      and the HA concentration (r = -0.45, t = 5.92, p < 0.001). The possible reasons
      for the low serum HAE activity and the raised serum HA concentration in patients
      with disseminated neoplasm and the negative correlation between the results are
      discussed.

PMID- 9027428
TI  - Glutamic acid decarboxylase autoantibody assay using 125I-labelled recombinant
      GAD65 produced in yeast.
AB  - We describe a new method for measuring autoantibodies (Ab) to the 65 kDa isoform
      of glutamic acid carboxylase (GAD65). In particular, GAD65 without the
      hydrophobic N-terminal region has been produced in yeast, purified, labelled with
      125I and reacted with GAD65 Ab. Antibody bound 125I-GAD65 is then precipitated by
      the addition of solid phase protein A. With the assay, GAD65 Ab were detected in
      59 of 71 (83%) islet cell antibody (ICA) positive IDDM patients and in 8 of 23
      (35%) ICA negative IDDM patients (overall 67 of 94 (71%) of IDDM patients). Low
      concentrations of GAD65 Ab were also detected in 2/98 (2%) healthy blood donors
      and 1/27 (4%) Graves' disease patients had a high level of antibody. GAD65 Ab
      were not detected in any of 10 Hashimoto's thyroiditis, 20 Addison's disease or
      19 myasthenia gravis sera. There was good agreement between the 125I assay and
      the current reference method based on 35S-labelled full-length GAD65 (produced by
      in vitro transcription/translation reaction) and solid phase protein A (r = 0.91,
      n = 108). Overall, our 125I assay showed sensitivity, precision and disease group
      specificity at least as good as any assay so far described. These features,
      combined with a simple assay protocol and the convenience of 125I counting and
      handling indicate that the method is suitable for routine GAD65 Ab measurements.

PMID- 9027429
TI  - Evaluation of reference values for erythrocyte glutathione.
AB  - The analytical, intra-individual and inter-individual variations as well as the
      best storage conditions were determined for erythrocyte glutathione, and the
      reference values were established. A total of 396 apparently healthy people, 206
      male, and 190 female, were randomly selected from villages and cities of the
      southern part of Turkey. The distribution was Gaussian and no significant
      difference was observed between the male and the female subjects. The mean
      (standard deviation) of the population investigated for glutathione was 6.9 (1.0)
      mumol/gHb. The analytical, intra-individual and inter-individual variations were
      assessed in 20 apparently healthy subjects and were found to be 4.63%, 13.67% and
      11.16%, respectively. Whole blood stored at -70 degrees C for up to 10 days was
      shown to be the best storage condition for erythrocyte glutathione determination.
      The results of the index of individuality showed that glutathione reference
      values could be used for diagnostic purposes.

PMID- 9027430
TI  - Lipoamide dehydrogenase activity in lymphocytes.
AB  - To assess the suitability of lymphocytes for patient diagnosis and carrier
      detection of lipoamide dehydrogenase deficiency, the activity of lipoamide
      dehydrogenase was determined in lymphocytes of six patients, seven obligate
      heterozygotes and 32 healthy controls. In healthy controls, lipoamide
      dehydrogenase activity was 80.7 +/- 23.6 nmol/min/mg protein, in obligate
      heterozygotes it was 36.0 +/- 12.1 nmol/min/mg protein and in the patients it was
      13.3 +/- 5.1 nmol/min/mg protein. For the purpose of standardization, the results
      were also calculated as lipoamide dehydrogenase/citrate synthase activity ratio.
      The activity of lipoamide dehydrogenase and the lipoamide dehydrogenase/citrate
      synthase ratio differed significantly between the three groups (P < 0.005). We
      conclude that lymphocytes are suitable for the diagnosis of lipoamide
      dehydrogenase deficiency and for carrier detection.

PMID- 9027431
TI  - The liver cell histones of diabetic patients contain glycation endproducts (AGEs)
      which may be lipofuscin components.

PMID- 9027432
TI  - Keeping up with drug allergy.

PMID- 9027433
TI  - Beta-blocker induced asthma: a role for sensory nerve hyperresponsiveness?

PMID- 9027434
TI  - Pollen allergy in South Africa.

PMID- 9027435
TI  - Drug-associated anaphylaxis: 20 years of reporting in The Netherlands (1974-1994)
      and review of the literature.
AB  - BACKGROUND: Since 1963, the Drug Safety Unit of the Dutch Inspectorate for Health
      Care (DSU) holds a voluntary reporting system. OBJECTIVE: To analyse all reports
      received in the years 1974 to 1994, registered as anaphylaxis or as a diagnosis
      that could contain cases of anaphylaxis. METHODS: All reports were classified as
      probable or possible anaphylaxis according to previously described criteria and
      the causal relationship between exposure and anaphylaxis was assessed. RESULTS:
      Nine hundred and ninety-two reports possibly concerning anaphylaxis were received
      between 1974 and 1994. Fifty-six were unclassifiable. The remaining 936 reports
      concerned 326 men and 610 women. Three hundred and forty-five reports were
      classified as anaphylaxis probable, 485 as anaphylaxis possible, and 106 as
      anaphylaxis unlikely by previously specified criteria. Drugs frequently
      associated with anaphylaxis (causal relationship certain or probable) were:
      glafenine (326 reports classified as anaphylaxis probable or possible),
      combination preparations with (propy)phenazone or propyphenazone/phenacetine
      (39), diclofenac (30), dextran (20), ibuprofen (14), floctafenine (12), allergen
      extracts (12), sulfamethoxazole with trimethoprim (12), and trimethoprim (11).
      There is probably substantial under-reporting as well as reporting bias in these
      data. Furthermore, many reports were classified as possible and not as probable
      anaphylaxis because the temporal relationship was unknown or not reported.
      CONCLUSION: Drugs that caused anaphylaxis most frequently were glafenine, NSAID
      and certain antibiotics. Data from a voluntary reporting system such as the DSU
      are valuable as an early warning system for drugs that may induce anaphylactic
      reactions.

PMID- 9027436
TI  - The clinical spectrum of anaphylaxis in north-west England.
AB  - OBJECTIVE: To assess the clinical spectrum of anaphylaxis with a view to
      developing management guidelines and as a foundation for an epidemiological
      study. METHODS: Study of the reaction histories and investigations of 172
      patients, including children and adults, referred because of anaphylactic
      reactions. RESULTS: Over 700 reactions occurred in 172 patients from age 5 months
      to 69 years. There were equal numbers of males and females; when ranked by age at
      worst reaction, the youngest quartile (0-4 years) was 75% male and the oldest
      quartile (40+ years) was 74% female. The severity of reactions graded
      continuously from fatal to mild One hundred and twenty of 172 had two or more
      reactions; the worst reaction was the first in 33, midsequence in 35 and the most
      recent in 52. Suspected causes of each patient's worst reaction associated with
      positive allergy tests include peanuts (42), tree nuts (23), other foods (25, in
      five associated with exercise), venoms (six bee, 22 wasp), muscle relaxants
      (seven) and latex (six). Twenty were classified as idiopathic and, in a further
      13, investigation of the suspected cause proved negative. There was doubt about
      the nature of some of the 'reactions' reported even though these had been treated
      as for anaphylactic reactions. CONCLUSION: The clinical spectrum of anaphylaxis
      has been defined for the area served by our unit. Management guidelines and
      future epidemiological studies will have to address the continuous distribution
      of severity of reactions, the wide age range and the multiplicity of causes.

PMID- 9027437
TI  - Intradermal challenge with interleukin-8 causes tissue oedema and neutrophil
      accumulation in atopic and non-atopic human subjects.
AB  - BACKGROUND: Interleukin-8 (IL-8) is a cytokine with potent neutrophil chemotactic
      and activating properties and is active in inflammatory conditions in man. It has
      been identified in human inflammatory skin conditions where it is likely to be
      responsible for both neutrophil recruitment from the circulation and possibly T
      lymphocyte chemoattraction. Studies in animals also suggest that IL-8 may augment
      skin oedema. OBJECTIVE: To study the effects of intradermally administered IL-8
      in humans on tissue oedema and cellular recruitment in atopic and non-atopic
      volunteers. METHOD: Interleukin-8 (1.2 x 10(-7) M) in the presence and absence of
      histamine was administered by intradermal injection. Wheal and erythema area were
      measured at regular intervals and 3 h following challenge punch biopsies were
      taken for immunocytochemistry. Cellular infiltrate was measured by
      immunocytochemical identification of neutrophils, eosinophils and T-lymphocytes
      in glycol-methacrylate-embedded sections. RESULTS: In the presence of histamine,
      IL-8 provoked a significantly greater wheal area when compared to that produced
      by histamine alone (P < 0.001). In the presence of histamine, IL-8 produced a
      significantly greater neutrophil infiltrate (P < 0.05), however, neither
      lymphocyte or eosinophil infiltration was found to be increased with IL-8
      challenge. There was no difference observed between atopic and non-atopic
      subjects, nor were any effects of IL-8 demonstrated in the absence of histamine.
      CONCLUSION: This study demonstrates that in human skin, IL-8 induces increased
      microvascular permeability and neutrophil infiltration, but not eosinophil or T
      lymphocyte chemoattraction.

PMID- 9027438
TI  - Detection of a kappa-casein-specific lymphocyte response in milk-responsive
      atopic dermatitis.
AB  - BACKGROUND: Bovine casein leads to an expansion of lymphocytes expressing the
      cutaneous lymphocyte antigen and to specific lymphocyte proliferation in a
      subgroup of patients with milk-responsive atopic dermatitis (AD). The casein
      fraction is composed of different proteins with defined and completely different
      sequences. OBJECTIVE: To define the stimulatory capacity of the major casein
      protein (alpha, beta and kappa) in lymphocyte proliferation assays with cells
      from milk-allergic and non-allergic individuals. METHODS: Proliferative responses
      of peripheral blood mononuclear cells to lipopolysaccharide-depleted casein
      subfractions were measured by thymidine incorporation. Lymphocytes from milk
      responsive patients with AD were compared with cells from non-responsive patients
      with AD and to non-atopic individuals. Atopic individuals with immediate symptoms
      following consumption of cow's milk were included as positive controls. Casein
      specific T-cell clones (TCC) from four patients with milk-responsive AD were
      restimulated with unfractionated casein and kappa-casein. RESULTS: Higher
      proliferative responses to unfractionated casein and alpha-, beta- and kappa
      casein were observed in milk-responsive patients compared with non-responders.
      Unfractionated casein and kappa-casein discriminated best between the milk
      responsive patients with AD and non-responders. Twenty-five of 31 TCG from
      patients with milk-responsive AD reacted to the mixed casein preparation and
      kappa-casein. CONCLUSION: A pronounced kappa-casein-specific T-cell-mediated
      immune response is found in the blood of many patients with a history of milk
      related exacerbation of AD.

PMID- 9027439
TI  - Survey of gastrointestinal reactions to foods in adults in relation to atopy,
      presence of mucus in the stools, swelling of joints and arthralgia in patients
      with gastrointestinal reactions to foods.
AB  - BACKGROUND: Food intolerance in adults is mostly associated with vague symptoms
      and not clearly related to atopy and food allergy. A combination of different
      pathogenetic mechanisms may be responsible for the symptoms. OBJECTIVE: The aim
      of this study was to describe patients with a history of food-related
      gastrointestinal symptoms in relation to the presence of mucus in the stools,
      joint swelling and arthralgia and to determine whether or not there is an
      association between the presence of these parameters, atopic disease and the
      presence of immune complexes in serum. METHODS: Fifty-eight patients
      consecutively referred to our clinic with food-related gastrointestinal symptoms
      were investigated. RESULTS: Thirty-five patients (60%) had mucus in their stools,
      24 patients (41%) complained about joint swelling and 41 patients (71%) had
      arthralgia. There were no correlations between these parameters and atopy
      according to Phadiatope test or skin prick test (SPT). No correlations were found
      between the occurrence of mucus in the stools, arthralgia and joint swelling.
      There were significantly higher levels of circulating immune complexes in
      patients with a history of arthralgia compared with patients with no such history
      (P < 0.03) and the number of individuals with the presence of such immune
      complexes was higher among the patients with arthralgia than among the patients
      without. In general the patients did not relate the exposure to certain foods to
      symptoms like joint swelling, arthralgia and presence of mucus in the stools.
      However, there were significant positive correlations between food-related
      gastrointestinal symptoms in the following instances: chocolate-induced
      gastrointestinal symptoms and mucus in the stools (P = 0.006), vegetable-induced
      gastrointestinal symptoms and mucus in the stools (P = 0.002) and meat-induced
      gastrointestinal symptoms and mucus in the stools (P = 0.003). In a group of
      individuals without food-related symptoms investigated separately, a very low
      frequency of mucus in the stools, joint swelling and arthralgia was seen (none,
      two and three individuals of the 20 subjects, respectively). Of 41 patients with
      immediate onset of gastrointestinal symptoms, 20 were atopic according to
      Phadiatope and SPT. Of 11 patients with late onset of symptoms 10 were negative
      in Phadiatope and SPT (P < 0.05). The most frequently involved foods were fruits,
      vegetables, milk, fish and meat. CONCLUSION: The results suggest the involvement
      of different inflammatogenic mechanisms in food-related gastrointestinal
      symptoms.

PMID- 9027440
TI  - Comparison between hypertonic and isotonic saline-induced sputum in the
      evaluation of airway inflammation in subjects with moderate asthma.
AB  - BACKGROUND: Hypertonic saline-induced sputum has recently been used for the
      evaluation of airway inflammation in asthma. OBJECTIVE: To assess the effect of
      hypertonicity on airway inflammation. METHODS: We compared the inflammatory cell
      composition of hypertonic saline-induced sputum with that of isotonic saline
      induced sputum in 21 asthmatic subjects and, at baseline and 30 min after each
      sputum induction, we measured bronchial hyper-responsiveness to methacholine as
      an indirect marker to detect increased airway inflammation. On two different
      days, the patients inhaled hypertonic saline (3-5% NaCl) or isotonic saline (0.9%
      NaCl) for 30 min via an ultrasonic nebulizer, while monitoring FEV1. Sputum was
      collected for inflammatory cell analysis. RESULTS: There was no difference in
      inflammatory cell percentages obtained with the two methods. Eosinophils were >
      1% in 20 subjects after hypertonic saline and in 16 subjects after isotonic
      saline, but this difference was not statistically significant. Intraclass
      correlation coefficients for sputum inflammatory cells obtained with the two
      methods were +0.642 for eosinophils, +0.644 for neutrophils, +0.544 for
      lymphocytes and +0.505 for macrophages. Hypertonic saline induced
      bronchoconstruction in a significantly greater number of subjects than isotonic
      saline. Also, hypertonic saline increased bronchial responsiveness to
      methacholine, while isotonic saline did not. CONCLUSION: We conclude that
      hypertonicity does not affect sputum cell composition, suggesting that
      inflammatory cells in hypertonic saline-induced sputum are probably preexisting
      and not acutely recruited in the airways by the hypertonic stimulus. However, the
      bronchoconstriction and the increase in bronchial hyper-responsiveness after
      hypertonic saline inhalation may imply the release of inflammatory mediators.
      This fact must be considered in the evaluation of soluble markers of inflammation
      in hypertonic saline-induced sputum.

PMID- 9027441
TI  - Isolation, cDNA cloning and expression of Lig v 1, the major allergen from privet
      pollen.
AB  - BACKGROUND: An olive allergen-like protein has been detected in privet pollen.
      This protein could be involved in the allergenic cross-reactivity described for
      privet and olive tree pollen extracts. OBJECTIVE: Isolation and characterization
      of natural Lig v 1. Cloning and expression of its cDNA in order to assess its
      structural similarity with the olive allergen. METHODS: Current chromatographic
      methods were used to isolate the privet counterpart of Ole e 1. A pool of sera
      from subjects allergic to olive tree pollen was used to immunodetect the protein
      in the elution profiles. Ole e 1-specific polyclonal antibody and allergic sera
      were used in immunoblotting assays of the isolated protein. Polymerase chain
      reaction amplification of the first strand cDNA synthesized from the privet
      pollen total RNA was carried out to prepare a full-length fragment encoding Lig v
      1. After nucleotide sequencing, expression of one clone was performed in
      Escherichia coli, under the form of a fusion protein with glutathione S
      transferase. The IgE binding capability of the recombinant protein was also
      analysed. RESULTS: The major allergen from privet pollen. Lig v 1, was purified
      to homogeneity by two gel filtration chromatographies and one reverse-phase high
      performance liquid chromatography. Its amino acid composition and N-terminal
      amino acid sequence were determined. Two different clones encoding Lig v 1 were
      sequenced. Strong sequence similarity between Lig v 1 and Ole e 1 was observed,
      the identity being 85 and 96%. One of the sequenced clones was expressed and the
      recombinant product exhibited IgG and IgE binding activities against both anti
      Ole e 1 polyclonal antibodies and olive-allergic sera. CONCLUSION: Privet pollen
      contains a protein structurally and immunologically related to the major allergen
      of olive pollen. The similarity exhibited by these proteins could explain the
      cross-reactivity observed between the two pollen extracts. Since these allergens
      are highly polymorphic, the expression of an immunologically active recombinant
      Lig v 1 will permit the preparation of well defined molecules for both research
      and clinical purposes.

PMID- 9027442
TI  - Automated specific IgE assay with recombinant allergens: evaluation of the
      recombinant Aspergillus fumigatus allergen I in the Pharmacia Cap System.
AB  - BACKGROUND: We report the results of a study comparing the recombinant
      Aspergillus fumigatus allergen 1 (rAsp f I) to commercial A. fumigatus extracts
      in serological assays. Pharmacia CAP System and skin tests. OBJECTIVE: The study
      was designed to test the feasibility of using recombinant allergens in an
      automated serology system for determination of allergen-specific IgE. METHODS:
      Patients with allergic bronchopulmonary aspergillosis (ABPA), asthmatics with A.
      fumigatus allergy and control subjects, who included allergic asthmatics without
      allergy to A. fumigatus and healthy subjects, were investigated. All subjects
      were characterized with respect to their total IgE level, radio allergosorbent
      test to A. fumigatus and skin test reactivity to both commercial A. fumigatus
      extracts and recombinant rAsp f I protein. RESULTS: All patients with ABPA (n =
      30) showed positive skin test reactions with commercial A. fumigatus extracts,
      and 24 were sensitized to rAsp f I by the same criterion. The 10 patients with
      asthma and A. fumigatus allergy showed positive skin reactions to at least one
      commercial extract, and five reacted to rAsp f I. All control subjects (n = 19)
      scored negatively in skin tests to A. fumigatus extracts and rAsp f I and showed
      no detectable rAsp f I-specific IgE. ImmunoCAP carrying immobilized rAsp f I were
      evaluated using sera from all individuals described and the results compared with
      those obtained with the rAsp f I-specific ELISA for IgE. The data obtained with
      the two rAsp f I-specific detection systems correlated closely (r = 0.997) and
      were in perfect agreement with the skin test results. CONCLUSION: The data show
      that rAsp f I can be used as immobilized allergen in the Pharmacia CAP System
      indicating the feasibility of using recombinant allergens for an automated
      serological diagnosis of allergic diseases. However, every recombinant allergen
      needs to be evaluated individually for its performance if applied to a new
      diagnostic technology.

PMID- 9027443
TI  - Comparison between two automated systems to determine specific IgE: CAP and
      ELItest.
AB  - BACKGROUND AND OBJECTIVE: The ELItest is a newly developed system to measure
      specific IgE based on allergen bound to paper rings and an alkaline phosphatase
      conjugated second antibody detection system. It was compared to the CAP system, a
      method based on allergen conjugated to an encapsulated cellulose polymer and a
      beta-galactosidase conjugated fluorescence detection system. METHODS: Sera of 300
      patients with positive history and positive skin-prick tests to common allergens
      (birch, timothy-grass, cat dander, dermatophagoides ptronyssinus, wasp venom) and
      30 negative controls were tested in both systems. Serial dilutions of high titre
      sera were measured; inter- and intraassay coefficients of variation (cv) were
      determined. RESULTS: The CAP system proved to be more sensitive (92.3%) compared
      to ELItest (84%) but marginally less specific (94.7% for CAP versus 96.7% for
      ELItest). Intraassay cv were slightly lower in the ELItest (7.2% CAP versus 6.4%
      ELItest), whereas the interassay cv was roughly twice as high for ELItest (20.1%)
      than for the CAP system (11.4%). Linearity over an 8-fold dilution was good in
      both tests (r2 0.979 ELItest versus 0.996 CAP), although ELItest levelled off at
      higher allergen concentrations. Similarly, correlation analysis between both
      systems revealed that ELItest consistently measured lower values, especially at
      higher concentrations of specific IgE. The slope of the linear regression line of
      a log/log plot of measured IgE concentrations was significantly lower than 1 in
      birch, cat and wasp; the y-intersect was significantly lower than 0 in all
      analysed allergens. CONCLUSION: These results suggest that the ELItest system for
      the measurement of specific IgE is not quite as reproducible and sensitive as the
      CAP system but slightly more specific, and that higher concentrations of specific
      IgE are measured lower in the ELItest. One potential reason might be that the
      amount of allergen bound to a paper ring might be smaller than that bound to a
      cellulose polymer, but further experiments are necessary to prove this
      hypothesis.

PMID- 9027444
TI  - Role of sensory neuropeptides in post-allergic propranolol-induced
      bronchoconstriction in guinea pigs in vivo.
AB  - BACKGROUND: Administration of propranolol can provoke bronchoconstriction in
      asthmatic patients. We hypothesized that such bronchoconstriction may result from
      the inflammatory mediators released by an allergic reaction. We recently
      developed a guinea pig model for propranolol-induced bronchoconstriction (PIB).
      Neuropeptides which are released from C-fibre nerve endings have been postulated
      to induce bronchial hyperresponsiveness through neurogenic inflammation.
      OBJECTIVE: The purpose of this study was to examine whether sensory neuropeptides
      are involved in the development of PIB after allergic reaction. METHODS:
      Propranolol at a concentration of 10 mg/ml was inhaled 20 min after antigen
      challenge in passively sensitized, anaesthetized and artificially ventilated
      guinea pigs. The animals were treated intravenously with a NK1 and NK2 dual
      antagonist, FK224, in a dose of 1 or 10 mg/kg or vehicle or a selective NK1
      antagonist, FK888, in a dose of 1 or 10 mg/kg or vehicle 10 min before or 15 min
      after antigen challenge. RESULTS: Propranolol inhaled 20 min after antigen
      challenge caused bronchoconstriction. FK224 or FK888 administered 15 min after
      antigen challenge as well as 10 min before antigen challenge did not reduce the
      PIB. CONCLUSION: We conclude that neuropeptides such as neurokinin A and
      substance P do not directly contribute to the development of PIB after allergic
      reaction.

PMID- 9027446
TI  - A role for the sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme
      in degranulation of rat basophilic leukaemia cells.
AB  - BACKGROUND: A circulating inhibitor of the sodium, potassium adenosine
      triphosphatase (Na+,K+ ATPase) enzyme has been described in allergic subjects.
      Recent studies have suggested that the Na+,K+ ATPase, enzyme may be involved in
      the signal transduction pathways of various cell types and that inhibition of its
      activity can modulate histamine release from basophils and mast cells. OBJECTIVE:
      The purpose of this study was to determine if modulation of Na+,K+ ATPase
      activity alters degranulation in the 2H3 subline of rat basophilic leukaemia
      cells (RBL-2H3), a mucosal mast cell model bearing high-affinity Fc receptors for
      IgE. METHODS: Degranulation was measured by the release of both exogenous
      serotonin and endogenous histamine. Na+,K+ ATPase activity was assessed by
      ouabain-sensitive [86rubidium] uptake ([86Rb] uptake) and ex situ enzyme
      activity. RESULTS: Ouabain-sensitive [86Rb] uptake and degranulation increased in
      parallel and in a dose-response fashion with increasing Fc receptor cross
      linking. Additionally, incubation with ouabain, a known inhibitor of Na+,K+
      ATPase activity, decreased both anti-IgE and calcium ionophore-induced
      degranulation, but increased spontaneous degranulation, each in a dose-response
      manner. Moreover, the effect of ouabain on degranulation was reversed by rinsing
      and mimicked by other known inhibitors of Na+,K+ ATPase activity. Finally, in the
      absence of anti-IgE or calcium ionophore, stimulation of ouabain-sensitive [86Rb]
      uptake by the sodium (Na+) ionophore monensin was associated with a corresponding
      dose-response increase in ouabain-sensitive degranulation. These experiments
      demonstrate that ouabain-sensitive [86Rb] uptake increases following IgE receptor
      cross-linking in RBL-2H3, and that factors which modulate Na+,K+ ATPase activity
      in these cells may also regulate degranulation. CONCLUSION: The results of this
      study suggest an important role for Na+,K+ ATPase activation in the signal
      transduction pathway of stimulated RBL-2H3.

PMID- 9027445
TI  - Granulocyte function in the airways of allergen-challenged pigs: effects of
      inhaled and systemic budesonide.
AB  - BACKGROUND: Late airways obstruction and eosinophil infiltration after allergen
      challenge are often seen in human asthma and animal models of allergy. This
      inflammatory reaction, which may be a link between acute and chronic asthma, is
      blocked by glucocorticoid pretreatment. However, the role of eosinophils in late
      airways obstruction and the primary site of action of glucocorticoids, i.e.
      locally or systemically, have not been fully determined. OBJECTIVES: This study
      was initiated to find out the role of eosinophils and neutrophils in allergen
      induced late airways obstruction in the pig. The effect of pretreatment with
      budesonide (BUD) given locally or systemically on cellular responses seen within
      8 h after allergen challenge was also studied. METHODS: Twenty-five minipigs were
      actively sensitized with Ascaris suum antigen and challenged under anaesthesia
      with antigen in the lower airways. Pigs were given BUD as an aerosol (10
      micrograms/kg) or an intravenous infusion (5 micrograms/kg) 1 h before allergen
      challenge. In one group, high doses of BUD (50 micrograms/kg) were infused twice
      with a 3-h interval before allergen challenge. As a positive control, one group
      was given the BUD vehicle as an infusion and as a negative control, one group not
      treated with BUD was given the irrelevant antigen ovalbumin. Eosinophils and
      neutrophils in lung tissue specimens were detected and levels of eosinophil
      peroxidase (EPO) and myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) fluid
      were measured using specific antibodies against porcine EPO and MPO. RESULTS: The
      number of eosinophils in lung tissue and BAL fluid and the level of EPO in BAL
      fluid were significantly increased 8 h after A. suum challenge in pigs not
      treated with BUD. With regard to possible recruitment and activation of
      neutrophils the only significant finding was an increase in the number of cells
      in BAL fluid. The eosinophil numbers and the level of EPO in BAL fluid were shown
      to be decreased by all BUD treatments in all the compartments studied compared to
      the positive control. However, the number of eosinophils in lung tissue and EPO
      levels in BAL fluid did not correlate with the magnitude of the late airways
      obstruction. CONCLUSION: Although eosinophils are present in the bronchial wall
      and lumen and are apparently activated, a causative relationship between this
      granulocyte and the late bronchial obstruction could not be established in this
      model.

PMID- 9027465
TI  - Shaker mice and a peek into the House of Usher.

PMID- 9027466
TI  - Characterization of embryonic stem-like cell lines derived from embryoid bodies.
AB  - Embryoid bodies (EB) were formed by TT2 embryonic stem (ES) cells in vitro. ES
      like cell lines (ESLC) were established by culturing cells obtained by
      disaggregation of EB at 4, 8 and 20 days after culture, and designated ESLC4,
      ESLC8 and ESLC20, respectively. Flow cytometric analysis indicated that the cell
      surface expression of Le(a) on ESLC was less than that of original TT2 ES cells,
      but the expression of L-CAM was comparable. After suspension culture, all of the
      ESLC cells formed cystic EB in vitro. In addition, some ESLC4- and ESLC8-derived
      EB showed signs of beating. Although coat color chimeras were able to be produced
      with ESCL4 at a lower rate than parental ES cells, the cells did not contribute
      to germ line cells in chimeras. These results suggest that the ESLC had less
      pluripotent than parental ES cells and also that EB formation is not useful in
      obtaining pluripotent cells.

PMID- 9027467
TI  - Germ-line contribution of embryonic stem cells in chimeric mice: influence of
      karyotype and in vitro differentiation ability.
AB  - The effect of the karyotype and the ability to differentiate in vitro upon germ
      line transmission by A3-1 embryonic stem (ES) cells in chimeric mice were
      examined. Germ-line transmission was confirmed in ES cells exhibiting 38% and
      more of the normal karyotype, but no chimeric mice and/or germ-line transmitters
      were observed regardless of the karyotype when the cystic embryoid body (CEB) was
      formed on day 8 and later in the suspension culture. Germ-line transmission of
      the ES cells was not significantly influenced by formation of the simple embryoid
      body (SEB). Germ-line transmitters were preferentially observed in chimeras when
      the ES cell contribution to coat color was markedly increased, but this
      contribution to coat color varied regardless of the karyotype or in vitro
      differentiation ability. These results suggest that A3-1 ES cells which exhibit
      CEB at 7 days after suspension culture and approximately 40% of normal karyotype
      are capable of germ-line transmission in chimeric mice.

PMID- 9027468
TI  - Histochemical observations of alkaline phosphatase activity of Echinococcus
      multilocularis during in vivo development in golden hamsters, an alternative
      definitive host.
AB  - Histochemical observations of alkaline phosphatase activity of Echinococcus
      multilocularis during the in vivo development in golden hamster, an alternative
      definitive host. The present work reports on the ability of protoscoleces from a
      European fox strain of E. multilocularis to differentiate and develop into the
      adult form in the small intestine of male golden hamsters treated with
      prednisolone. Detection of alkaline phosphatase activity on various stages of the
      developing worm was performed by histochemical methods. The enzyme activity was
      not demonstrable in the early stages of infection but occurred with
      strobilization. Age-related changes in the distribution of the enzyme activity
      took place during strobilization. Alkaline phosphatase activity was evident in
      the excretory ducts of 8 to 11 day old strobila and in the tegument of mature
      proglottis of 16 day old worms. This in vivo procedure with rodents as definitive
      hosts provides interesting preliminary results on the biology of the E.
      multilocularis adult. Further investigations on membrane-bound enzymes involved
      in physiological and nutritional processes are in progress.

PMID- 9027469
TI  - Detection of proviruses and viral RNA in the early stages of feline
      immunodeficiency virus infection in cats: a possible model of the early stage of
      HIV infection.
AB  - Feline immunodeficiency virus (FIV) infection in cats has been reported to be a
      useful animal model for human AIDS studies, especially in the early stages of
      infection. We examined the temporal changes in provirus detection in peripheral
      blood mononuclear cells (PBMC) and the distribution of FIV-DNA and RNA in feline
      tissues by the polymerase chain reaction at 10, 35, 70 days after intravenous
      inoculation of FIV. Viral DNA in the PBMC was detected three to four weeks after
      infection and its fluctuation was demonstrated for the first time. Ten days after
      infection, before seroconversion, proviruses were detected only in the mesenteric
      lymph nodes and intestines. At 35 and 70 days after infection, after
      seroconversion, proviruses were detected in most lymphoid organs and the salivary
      glands, but the expression of FIV-RNA was limited to the thymus at 70 days after
      infection. These results show that FIV-RNA is transcribed from proviral DNA
      exclusively in the thymus at this stage. We suggest that the quantitative changes
      in detectable proviruses in the PBMC depend on the relation between the decrease
      in infected cells caused by cytolytic T lymphocytes and/or apoptosis and their
      increase caused by the release of a new supply of lymphocytes from the thymus.

PMID- 9027470
TI  - Heredity of red blood cells with high K and low glutathione (HK/LG) and high K
      and high glutathione (HK/HG) in a family of Japanese Shiba Dogs.
AB  - Forty-two of 81 dogs from a family of Japanese Shiba dogs had red blood cells
      with a high K and a low Na concentration (HK). Of the HK dogs, 32 were high K and
      low glutathione (HK/LG) and 10 were high K and high glutathione (HK/HG). These
      variants were found in both males and females. The phenotype of HK was inherited
      in a recessive mode as reported earlier. A high incidence of HK/LG dogs was found
      in this family, and the phenotype was also inherited in a recessive mode.
      Glutamate (Glu) influx, which defines the cellular glutathione concentration, was
      lower in HK/LG cells than in HK/HG cells (in some cases extremely low). The fact
      that the red blood cells of HK/LG dogs have the two varying characteristics of a
      remaining Na, K-pump and low Glu transport suggests that 2 or more genes may be
      involved. Since an extremely low Glu influx was also found in normal low K and
      high Na (LK) red blood cells, the characteristic of low Glu transport also exists
      in LK cells. The phenotype of low Glu transport may also be inherited in a
      recessive mode. This family therefore had a very high incidence of homozygous
      recessive genes which control the phenotypes for the Na, K-pump and low Glu
      transport.

PMID- 9027471
TI  - Changes in normal vaginal flora of African green monkeys (Cercopithecus aethiops)
      during the menstrual cycle.
AB  - Changes in normal vaginal flora of African green monkeys associated with the
      estrous cycle were examined by the swab method. Bacteroidaceae, corynebacteria,
      and streptococci were predominant throughout the whole estrous cycle, although
      individual differences were great. It was also clear that all bacterial species
      tended to decrease in the menstrual phase. Lactobacilli, the most predominant
      bacteria in the normal vagina of humans, were detected only in very low numbers
      in the African green monkey, suggesting that the normal vagina of the African
      green monkey has a different ecosystem from that of normal human vaginal flora.

PMID- 9027472
TI  - Epitope mapping of murine monoclonal antibodies against human immunodeficiency
      virus type 1 Nef.
AB  - It has shown that the human immunodeficiency virus type 1 (HIV-1) Nef protein has
      the high antigenicity in HIV-1 seropostive individuals. We newly obtained seven
      monoclonal antibodies (mAbs). To identify the antigenic determinants of HIV-1 Nef
      protein against murine, epitope mapping of the mAbs was performed by enzyme
      linked immunosorbent assay (ELISA) by using several recombinant truncated Nef
      fusion proteins, that were expressed in Esherichia coli, and synthetic peptides.
      The results showed that mAbs A6, A7, F2, F3, F4, F8 and E5 recognized epitopes on
      Nef protein located at amino acid residues 18-26, 28-45, 115-137, 128-137, 115
      126, 128-137, and 170-181, respectively.

PMID- 9027473
TI  - Age-related appearance of dystrophic axon terminals in cerebellar and vestibular
      nuclei of Mongolian gerbils.
AB  - In the brains of 360-day-old Mongolian gerbils, numerous swellings immunoreactive
      to anti-neurofilament antibody were observed in cerebellar and vestibular nuclei.
      The number of these swellings was the same in two gerbil strains with different
      susceptibility to spontaneous motor seizures by various stimuli, but much more
      numerous in gerbils as compared with the 360-day-old Slc:Wistar rats. Such
      swellings were only occasionally found before 60 days of age in gerbils, but they
      increased in number about fivefold from 60 to 180 days of age and about quadruple
      from 180 to 360 days of age. Electron microscopic observation showed that these
      swellings were dystrophic axon terminals (DATs) whose cytoplasms were occupied
      with large bundles of neurofilaments, numerous vesicular structures containing
      membranous and/or granular materials, and many rod-shaped mitochondria.
      Additionally, other types of DATs displaying degenerative changes of cytoplasmic
      organelles were observed. ACPase cytochemistry showed that the vesicular
      structures in the DATs contained ACPase and released it into the cytoplasm.

PMID- 9027474
TI  - The effects of medetomidine on maternal and fetal cardiovascular and pulmonary
      function, intrauterine pressure and uterine blood flow in pregnant goats.
AB  - To investigate the effects of medetomidine on late pregnant goats, medetomidine
      induced changes in maternal or fetal circulation and acid-base balance, as well
      as changes in intrauterine pressure (IUP) and uterine blood flow (UBF), were
      studied. Intramuscular administration of medetomidine (40 micrograms/kg b.w.)
      decreased the heart rate (HR) and arterial blood pressure (ABP) of the mother,
      and the change in HR was significant statistically (p < 0.05). In the fetus, HR
      and ABP showed a transient decrease and increase (p < 0.05), respectively. A
      decrease in maternal arterial blood pH and oxygen partial pressure (PO2) and an
      increase in carbon dioxide partial pressure (PCO2) were recorded after the
      injection, but none was significant. In the fetus, arterial blood PO2 decreased
      significantly (p < 0.05) after 5 min of administration, and a significant
      metabolic acidemia supported by a decrease in base excess was observed. Within 1
      to 4 min after the administration of medetomidine, IUP began to rise and remained
      high for 10 to 14 min. Thereafter, the rise in IUP was frequent and periodical.
      After the injection, UBF significantly (p < 0.05) decreased, and the fall in UBF
      was associated with a rise in IUP. The maternal and fetal serum medetomidine
      concentration increased remarkably after the injection of medetomidine into the
      mother. These observations in late pregnant goats suggested that medetomidine
      induced a decrease in maternal cardiac output, a decrease in UBF arising from the
      induction of uterine contractions, and transplacental medetomidine can have a
      suppressive effect on the fetus.

PMID- 9027475
TI  - Genetic typing of the mouse ob mutation by PCR and restriction enzyme analysis.
AB  - A genetic typing method for the mouse obese (ob) mutation by PCR and restriction
      fragment length polymorphism (RFLP) analysis was developed. Three genotypes
      (ob/ob, ob/+ and +/+) of the ob mouse are rapidly differentiated with this assay.
      Since only a small biopsy specimen (tail end) is necessary for the genotyping,
      the ob mouse at any age is typable and can be used in subsequent breeding or
      research. Obese homozygotes (ob/ob) were efficiently produced by mating
      heterozygotes (ob/+) only, which were selected by using the PCR-RFLP assay.

PMID- 9027476
TI  - Detection of viral RNA by electron microscopic in situ hybridization (ISH-EM) in
      the germinal epithelium of mice infected with encephalomyocarditis (EMC) virus.
AB  - Electron microscopic in situ hybridization (ISH-EM) was first applied to the
      detection of viral RNA in the germinal epithelium of mice inoculated i.p. with
      10(5) plaque-forming units/mouse of the D variant of encephalomyocarditis virus
      (EMC-D). Signals of viral RNA were first detected in a small number of Sertoli
      cells showing mild degeneration at 2 days post inoculation, and 2 days later,
      they were also detected in germinal cells and spermatogonia when Sertoli cells
      showed prominent degeneration. The results clearly demonstrated that the first
      site of viral attack in the germinal epithelium was Sertoli cell in the case of
      EMC-D-induced mouse orchitis.

PMID- 9027478
TI  - Identification of rat serum alkaline phosphatase isoenzyme by means of wheat germ
      agglutinin.
AB  - Wheat germ agglutinin (WGA) precipitates bone type serum alkaline phosphatase
      (sALP) isoenzyme specifically. The precipitates are composed of the
      macromolecules of WGA and "bone type sALP" (WGA-ALP complex). In order to use
      bone type sALP as a marker in polyacrylamide gel electrophoresis (PAGE), a method
      to separate "bone type sALP" from the "WGA-ALP complex" was established by using
      N-acetyl-D-glucosamine (GlcNAc)-Sepharose 6E column chromatography. It was
      concluded that this method is useful for clinical examination in the rat.

PMID- 9027477
TI  - Efficacy of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) on an ARC/AIDS rhesus
      macaque (Macaca mulatta) infected with simian immunodeficiency virus.
AB  - The efficacy of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) was investigated in
      vivo by using a male ARC/AIDS rhesus macaque infected with simian
      immunodeficiency virus (SIVmac251/32H). He was administered subcutaneously 6-Cl
      ddG (50 mg/kg B.W.) every 8 hr for 14 days when he showed clinical features of
      recurrent weight loss, severe diarrhea and neuropathy. The number of CD4+, CD8+
      cells and total T cells increased rapidly after administration of 6-Cl-ddG and a
      high level was maintained for 2 months, but the B cell count decreased during the
      treatment. The antibody titer to SIV did not change significantly during or after
      the treatment, but the virus load in the plasma measured by RT-PCR dropped to one
      third at the start of the 6-Cl-ddG treatment. Within 3 days after the start of 6
      Cl-ddG administration, he began to show recovery in clinical signs including
      weight increase, and disappearance of diarrhea and neuropathy. These findings
      suggested that 6-Cl-ddG was effective at the stage of ARC/AIDS in a rhesus monkey
      infected with SIV.

PMID- 9027479
TI  - Dilute down lethal: a new lethal mutation in Japanese quail.
AB  - "Dilute down lethal (DDL)" is a new mutation of Japanese quail (Coturnix
      japonica). Neonatal plumage of the DDL mutant is the same as the wild type in
      pattern, but its coloration is slightly lighter than that of the wild type. In
      addition to the down color abnormality, some DDL chicks have bent digits. All DDL
      chicks die within three days of age. Genetic analysis revealed that the DDL
      mutation is controlled by an autosomal recessive gene. The proposed gene symbol
      is ddl.

PMID- 9027480
TI  - Molecular genetic mapping of the mouse male sterility and histoincompatibility
      (mshi) mutation on proximal chromosome 10.
AB  - The recessive male sterility and histoincompatibility (mshi) mutation in the
      mouse generates pleiotropic effects on histocompatibility and male reproduction,
      while female mutants appear to be reproductively normal. We have mapped the mshi
      mutation to mouse Chromosome (Chr) 10 by analysis of 126 progeny from an
      intraspecific backcross. Our analysis both places the male sterility and
      histoincompatibility controlled by mshi within a 20-cM interval between the
      markers D10Mit51/D10Mit212 and D10Mit170 and has allowed the ordering of several
      other microsatellite markers on Chr 10 that were previously unresolved. The high
      resolution backcross panel we describe should facilitate the isolation of more
      tightly linked probe sequences and, ultimately, the molecular identification of
      the gene or genes affected by this interesting mutation.

PMID- 9027481
TI  - Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are
      associated with distinct mitochondrial DNA haplotypes.
AB  - Because Wolfram (or DIDMOAD) syndrome is supposed to be a mitochondrial (mt)
      mediated disease, we investigated a group of eight DIDMOAD patients with respect
      to point mutations of the mtDNA thus far described as being associated with
      defined mitochondrial disorders such as MELAS, MERRF, and LHON. Furthermore, to
      screen DIDMOAD patients for other mtDNA defects we used Southern blot analysis to
      detect mtDNA length mutations and rearrangements as well as PCR-SSCP and direct
      sequencing to screen all ND genes (complex I of the respiratory chain), the 22
      tRNAs, and a part of the cyt b gene for unknown mutations. As a disease control
      group, 17 LHON patients (harboring one of the primary LHON mutations) were
      included in this study because of the overlapping clinical symptoms (optic
      atrophy) in both syndromes. We compared mtDNA variants identified in DIDMOAD
      patients with those found in LHON patients as well as in a control group
      consisting of 67 healthy German blood donors. In total, the control group was
      characterized by 29 polymorphic sites in ND and tRNA genes that define certain
      major Caucasian haplotypes. We found that a cluster of nucleotide exchanges at
      nucleotide positions (nps) 4216 and 11,251 roughly discriminates controls (12/67
      controls, 18%) from the disease groups (6/8 DIDMOAD patients, 75%; 10/17 LHON
      patients, 59%). All 4216-positive LHON patients (10 patients) were concentrated
      in a haplogroup defined by additional exchanges at nps 10,398, 12,612, and 13,708
      (haplogroup A), while the bulk of 4216-positive DIDMOAD patients (5 patients)
      were found in a distinct haplogroup consisting of nucleotide exchanges at nps
      4917, 10,463, 13,368, 14,233, and 15,928. The frequencies of both haplogroups
      were significantly lower in the control group versus the respective disease
      groups. A more detailed analysis was performed by sequencing the two
      hypervariable regions of the non-coding D-loop region from patients and controls
      and corroborated the ranging in the two major haplogroups. Thus, the different
      clinical features of the mitochondrial disease groups investigated here
      corresponded to different clusters of mtDNA variants, which might act as
      predisposing haplotypes, increasing the risk for disease.

PMID- 9027482
TI  - Characterization of a Mus spretus YAC that maps to the pseudoautosomal region.
AB  - A library, containing M. spretus DNA in a half-YAC vector, was made and screened
      for clones hybridizing with an oligomer of the telomere hexamer TTAGGG. FISH to
      metaphase spreads of spleen cells showed hybridization of clone YTY3 to the
      distal ends of both X and Y chromosomes, consistent with localization to the
      pseudoautosomal region (PAR). Recombinational mapping in the BXD RI strains and
      an interspecies backcross, using a plasmid subclone and PCR primers from YTY3,
      showed linkage to distal Chr X. The restriction map of the YAC contains three
      NotI sites. Sequences similar to Mov15 lie close to the vector end of the clone,
      while the other end contains a telomere array that appears to be interstitial
      within the PAR, suggesting that the insert represents a proximal portion of the
      PAR. Sequences homologous to the clone are also present at subtelomeric regions
      of autosomes 4, 9, and 13.

PMID- 9027483
TI  - Isolation of a novel Sry-related gene that is expressed in high-metastatic K-1735
      murine melanoma cells.
AB  - To identify genes differentially expressed in association with metastatic
      potential of K-1735 mouse melanoma cells, the mRNA differential display method
      was applied to compare mRNAs from high- and low-metastatic K-1735 cells. A novel
      gene was identified as being expressed in high-metastatic cells but not in low
      metastatic cells. Sequence analysis revealed that this gene had an open reading
      frame of 538 amino acid residues containing a Sry high-mobility group (HMG) box
      domain, known as a DNA binding motif, particularly in the Sox family genes. This
      gene showed the highest homology to the human SOX9 gene, which is the responsible
      gene for an inherited disease, campomelic dysplasia. Thus, this gene was
      designated the Sox21 gene (the 21st Sox family gene). The Sox21 gene was mapped
      to mouse Chromosome 15, to which neither genes containing the HMG box region nor
      the loci of hereditary diseases similar to campomelic dysplasia have been
      previously mapped. This gene was highly conserved and specifically expressed in
      the brain. These results suggest that expression of the Sox21 gene is involved in
      the development of nerve systems and may function to enhance the metastatic
      potential of K-1735 mouse melanoma cells of nerve cell origin.

PMID- 9027484
TI  - Genomic structure and evolution of a novel gene (PLA2L) with duplicated
      phospholipase A2-like domains.
AB  - In a previous study, we isolated a novel human cDNA with two domains of homology
      to secreted phospholipase A2 (sPLA2) embedded within a much larger open reading
      frame. The corresponding gene, termed PLA2L, is also unusual in that it is
      transcribed from an endogenous retroviral long terminal repeat promoter in
      teratocarcinoma cell lines. The associated retroviral element, a member of the
      HERV-H family of sequences, is found within an intron of the human PLA2L gene and
      has apparently assumed transcriptional regulatory functions at this locus. In
      this study we have isolated genomic clones spanning the human PLA2L locus and
      have determined the intron/exon structure of the PLA2-like domains. This
      intron/exon structure is very similar to that of known sPLA2s despite the fact
      that the PLA2L gene is highly diverged and has a novel duplicated structure. We
      also mapped PLA2L to chromosome 8q24, a location that differs from the known
      locations of human sPLA2s. Genomic PCR across primate species was performed to
      determine the approximate time of integration of the HERV-H element. Results
      indicate that the element integrated 15-20 million years ago since it is present
      in chimpanzee and gorilla but absent in orangutan and lower primates. Although
      the function of the PLA2L gene is not known, genomic Southern analyses suggest
      evolutionary conservation in mammals. These results contribute to our
      understanding of the unique and complex evolutionary history of the PLA2L gene.

PMID- 9027485
TI  - Comparative linkage mapping of human chromosome 13 and bovine chromosome 12.
AB  - A comparative linkage map of human chromosome 13 and bovine chromosome 12 was
      constructed using eight polymorphic microsatellite markers associated with six
      specific genes. Linkage of these was also examined relative to five previously
      mapped anonymous microsatellite markers. Seven gene-linked markers were developed
      from bovine large-insert genomic clones containing one of five genes of interest
      (serotonin receptor subtype 2, fms-related tyrosine kinase, coagulation factor
      10, retinoblastoma susceptibility gene, collagen type IV alpha 1), and one
      additional marker was developed from a microsatellite resident within an intron
      of the bovine dopachrome tautomerase gene. Four of these loci were previously
      assigned to bovine chromosome 12 by analysis of a somatic cell hybrid panel. This
      study provides linkage information for examining gene order in this conserved
      synteny group. The comparative linkage mapping results indicate that the q arm of
      human chromosome 13 is almost entirely conserved in bovine chromosome 12. One
      intrachromosomal rearrangement was detected in this linkage group relative to
      human, and this rearrangement was confirmed by fluorescence in situ hybridization
      results.

PMID- 9027486
TI  - A yeast artificial chromosome (YAC) contig encompassing the critical region of
      the X-linked lymphoproliferative disease (XLP) locus.
AB  - X-linked lymphoproliferative disease (XLP) is characterized by a marked
      vulnerability to Epstein-Barr virus (EBV) infection. Infection of XLP patients
      with EBV invariably results in fatal mononucleosis, agammaglobulinemia, or
      malignant lymphoma. Initially the XLP gene was assigned to a 10-cM region in Xq25
      between DXS42 and DXS37. Subsequently, an interstitial, cytogenetically visible
      deletion in Xq25 was identified in one XLP family, 43. In this study we estimated
      the deletion in XLP patient 43-004 by dual-laser flow karyotyping to involve 2%
      of the X chromosome, or approximately 3 Mb of DNA sequence. From a human
      chromosome Xq25-specific yeast artificial chromosome (YAC) sublibrary, five YACs
      containing DNA sequences deleted in patient 43-004 have been isolated. Sequence
      tagged sites (STSs) from these YACs have been used to identify interstitial
      deletions in unrelated XLP patients. Three more families with interstitial
      deletions were found. Two of the patients (63-003 and 73-032) carried an
      interstitial deletion of 3.0 Mb overlapping the 43-004 deletion. In one XLP
      patient (30-011) who exhibited the characteristic postinfectious mononucleosis
      phenotype of XLP with hypogammaglobulinemia and malignant lymphoma, a deletion of
      approximately 250 kb was detected overlapping the deletion detected in patients
      43-004, 63-003, and 73-032. A YAC contig of 2.2 Mb spanning the XLP critical
      region, whose orientation on chromosome X was determined by double-color
      fluorescence in situ hybridization and which consists of 15 overlapping YAC
      clones, has been constructed. A detailed restriction enzyme map of the region has
      been constructed. YAC insert sizes were determined by counter-clamped homogenous
      electric field gel electrophoresis. Chimerism of YACs was determined by FISH and
      restriction mapping. On the basis of lambda subclones, YAC end-derived plasmids,
      and STSs with an average spacing of 100 kb, a long-range physical map was
      constructed using 5 rare-cutter restriction enzymes. The STSs and lambda
      subclones were used in Southern hybridization and PCR analyses. The work
      presented here substantially refines the critical region for XLP. The YAC contig
      with the overlapping interstitial deletions constitutes the basis for the
      construction of a transcriptional map of the critical region and facilitates the
      identification of the XLP gene.

PMID- 9027487
TI  - Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome
      19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human.
AB  - Sipa1, previously called Spa1, is transcriptionally induced in the murine
      lymphoid cells following mitogenic stimulation and encodes a protein with a
      domain related to Rap1 GTPase activating protein (Rap1GAP) at the N-terminus and
      to PEST sequences followed by a leucine zipper motif at the C-terminus. Herein
      mouse genomic Sipa1, which consisted of 16 exons, was cloned. Gene linkage
      analysis using (BXD) recombinant inbred strains indicated that Sipa1 was mapped
      to the most centromeric region of chromosome 19 syntenic with the long arm of
      human chromosome 11. Human SIPA1 cDNA exhibited a striking homology to that of
      mouse throughout the entire region, with the overall identity being 90% at the
      amino acid level. Human genomic clones, which hybridized with both mouse and
      human SIPA1 cDNA but not with RAP1GAP cDNA, were then isolated. Fluorescence in
      situ hybridization (FISH) analysis using the human genomic clones indicated that
      SIPA1 was indeed mapped to chromosome 11q13, most likely to the 11q13.3
      subregion. It was further indicated by double-color FISH that SIPA1 was located
      in the centromeric neighborhood of CCND1/ PRAD1, a presumed BCL1 oncogene.

PMID- 9027488
TI  - Molecular cloning and characterization of the human AE2 anion exchanger (SLC4A2)
      gene.
AB  - The human AE2 gene (HGMW-approved symbol SLC4A2) encompasses over 17 kb and
      contains 23 exons intervened by 22 introns. The size range for the exons is 90
      255 bp, whereas that for the introns is 80 bp to 2.2 kb. Exon 1 consists solely
      of 5'-untranslated sequence, and exon 2 encodes the amino-terminal end of the
      antiport protein. Primer extension experiments suggest that there are multiple
      transcription initiation sites in leukocytes. The putative promoter region of the
      human AE2 gene contains no obvious TATA or CCAAT elements in the expected
      positions but has GC boxes, proposed sites for binding Sp1 transcription factor.
      These features, as well as the presence of several consensus elements such as
      GATA, LBP-1, E-box, CACC box, and T-antigen motif, indicate that the human AE2
      promoter resembles the erythroid promoter of the human AE1 gene. The human AE2
      gene (which has been previously mapped to chromosome 7) has three more introns
      than the human AE1 gene (mapped to chromosome 17), but downstream of intron 7 in
      the AE2 gene (corresponding to intron 4 in the AE1 gene), these two genes show a
      rather similar exon/intron organization.

PMID- 9027489
TI  - Human homology and candidate genes for the Dominant megacolon locus, a mouse
      model of Hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is a congenital disorder of the enteric nervous
      system characterized by the absence of enteric ganglia. Three genes for HSCR have
      been identified: the RET proto-oncogene, the gene coding for the endothelin B
      receptor (EDNRB), and the endothelin 3 gene (EDN3). In mice, natural and in vitro
      induced mutations affecting the Ret, Ednrb, and Edn3 genes generate a phenotype
      similar to human HSCR. Another model of HSCR disease is the Dominant megacolon
      (Dom), a spontaneous mouse mutation for which the target gene has not yet been
      identified. The Dom mutation has been mapped to the middle-terminal region of
      mouse chromosome 15, between D15Mit68 and D15Mit2. Using new or known
      polymorphisms for conserved human/mouse genes, we established the homology
      between the Dom locus and human chromosome 22q12-q13. Two genes, Smstr3 and Adsl,
      not previously mapped in the mouse genome, were located on mouse Chromosome 15.
      Three genes (Smstr3, Lgals1, and Pdgfb) are possible Dom candidates, as they do
      not recombine with the Dom mutation in a 252 Dom/+ animal backcross.

PMID- 9027490
TI  - The complete sequences of the galago and rabbit beta-globin locus control
      regions: extended sequence and functional conservation outside the cores of DNase
      hypersensitive sites.
AB  - The locus control region (LCR) of mammalian beta-globin genes covers at least 17
      kb at the 5' end of the gene cluster and has been implicated in chromatin domain
      opening, enhancement, and insulation from neighboring sequences. Functional
      dissection of the LCR has defined the minimal cores for four of the five major
      DNase hypersensitive sites (HSs) that mark this regulatory region. To examine
      fully the patterns of conserved sequences in the mammalian homologs to the beta
      globin LCR, we determined the complete DNA sequence of the galago beta-globin LCR
      and completed previously unsequenced regions of the rabbit LCR. Simultaneous
      alignment of these sequences with the human, goat, and mouse LCRs revealed
      conserved sequences (phylogenetic footprints) detected using three largely
      independent methods. The most highly conserved segments are found both within the
      HS cores and in some but not all regions flanking the cores. These results argue
      for an extended pattern of well-conserved sequences, many of which lie outside
      the minimal cores, and we show that a key sequence required for domain opening by
      the region including HS3 maps about 1 kb 5' to the minimal core. Differential
      phylogenetic footprints, containing sequences conserved in nonhuman mammals but
      not in humans, are found primarily around HS3, consistent with some species
      specific differences in function that may be important for differences in
      hemoglobin switching during development.

PMID- 9027491
TI  - Genomic cloning and chromosomal assignment of the E2F dimerization partner TFDP
      gene family.
AB  - The TFDP genes encode a family of transcription factors that can form
      heterodimers with E2F family proteins in vivo. The E2F-TFDP transcription factors
      are major regulators of genes that are required for the progression of S-phase,
      such as DHFR and DNA polymerase alpha, and they play a critical role in cell
      cycle regulation and differentiation. The retinoblastoma tumor suppressor protein
      has been shown to induce growth arrest by binding to E2F-TFDP and repressing its
      activity. Two human TFDP genes have been cloned, namely TFDP1 and TFDP2 (or DP1
      and DP2). In the present study, we identified genomic clones of TFDP1, its
      pseudogene TFDP1P and TFDP2, and we mapped them to chromosome 13q34, 1q32.3, and
      3q23, respectively. Chromosomal abnormalities involving regions 13q34 and 3q23
      have been reported in certain lymphomas and other diseases associated with loss
      of cell cycle regulation, and the involvement of the TFDP transcription factors
      remains to be elucidated.

PMID- 9027492
TI  - Isolation of novel genes from the CMT1A duplication/HNPP deletion critical region
      in 17p11.2-p12.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1.5-Mb tandem
      DNA duplication in chromosome 17p11.2-p12, while hereditary neuropathy with
      liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this
      locus. The 1.5-Mb CMT1A monomer unit duplicated in CMT1A and deleted in HNPP is
      flanked by low-copy repeats termed CMT1A-REPs. Both diseases appear to be caused
      by an altered copy number of the peripheral myelin protein 22 gene (PMP22), which
      lies within the critical region. To identify additional genes rapidly, we used a
      cosmid contig of this region and reciprocal probing of arrayed chromosome 17
      specific cosmid and cDNA libraries. Three cDNA clones were identified within the
      CMT1A duplication/HNPP deletion region and one just proximal to the critical
      region. The cDNA for human heme A:farnesyltransferase (COX10) mapped 10 kb
      centromeric to the distal CMT1A-REP. The other two cDNA clones from within the
      critical interval mapped to cosmid 126D1 at the mfd41 (D17S261) DNA marker, and
      their conceptual translation showed homology to 60S ribosomal protein L9 (RPL9)
      and chromosomal protein RMSA-1 (RMSA-1). A gene that is homologous to human
      peroxisome proliferator activated receptor alpha (hPPARA) was identified near the
      proximal CMT1A-REP.

PMID- 9027493
TI  - Isolation and regional mapping of cDNAs expressed during early human development.
AB  - A cDNA sequencing project was initiated with the aim of isolating and mapping new
      genes expressed during early human development. A human embryo cDNA library was
      constructed, and a prescreening procedure was used to select cDNAs corresponding
      to poorly transcribed genes. Partial sequences were generated from one or both
      ends of 231 cDNA clones, and sequence comparison with genetic databases revealed
      that 28% were already annotated genes, 42% matched with partial sequences
      expressed sequence tags that had already been detected, 3% contained no insert,
      5% were highly similar to sequences from other species, and 23% of the cDNAs
      appeared to be unknown in genetic databases. All new sequences were deposited in
      public genetic databases, and most of the corresponding cDNAs were regionally
      mapped on human chromosome bands using both fluorescence and radioactive in situ
      hybridization. Several cDNAs colocalized with critical regions of the genome
      regarding mapped disorders, thus providing candidate genes for human genetic
      diseases.

PMID- 9027494
TI  - Molecular cloning and chromosomal localization in human and mouse of the SH2
      containing inositol phosphatase, INPP5D (SHIP). Amgen EST Program.
AB  - The action of lipid phosphatases on inositol phosphates is thought to be one
      method that the cell uses to attenuate growth factor- or cytokine-induced
      mobilization of calcium. We have cloned a cDNA from a mouse spleen library that
      is virtually identical to the recently described inositol tetraphosphate and
      phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase, SHIP. Chromosomal
      localization studies in human and mouse by FISH mapping and interspecies
      backcrossing in mice have demonstrated that human SHIP is localized to 2q36-q37.1
      and that mouse SHIP is localized to 1C5.

PMID- 9027495
TI  - The human inward rectifying K+ channel Kir 2.2 (KCNJ12) gene: gene structure,
      assignment to chromosome 17p11.1, and identification of a simple tandem repeat
      polymorphism.
AB  - K+ channels are essential for a variety of cellular functions in both excitable
      and nonexcitable cells, and K+ channel gene alteration has been recently
      described in cardiac and neurological disorders. To explore further the relations
      between hereditary human diseases and K+ channels, we isolated from a human
      cosmid library the gene encoding the inwardly rectifying K+ channel alpha-subunit
      Kir 2.2 (KCNJ12). PCR analysis performed on this clone indicates that the entire
      open reading frame is contained in one unique exon. A polymorphic (CA)16 sequence
      was localized 2.2 kb upstream of the ATG start codon. Fluorescence in situ
      hybridization on human metaphases assigns the gene to band 17p11.1. The
      implication of a deletion of the Kir 2.2 gene in the Smith-Magenis syndrome,
      which is also localized at 17p11, is unlikely since a Kir 2.2-linked
      microsatellite sequence could be amplified from the DNA of a Smith-Magenis
      syndrome affected patient bearing a 17p interstitial deletion.

PMID- 9027496
TI  - Mapping of a newly discovered human gene homologous to the apoptosis associated
      murine mammary protein, MFG-E8, to chromosome 15q25.

PMID- 9027497
TI  - Mapping of the Ras-GRF2 gene (GRF2) to mouse chromosome 13C3-D1 and human
      chromosome 5q13, near the Ras-GAP gene.

PMID- 9027498
TI  - Mapping of the human ribosomal small subunit protein gene RPS24 to the chromosome
      10q22-q23 boundary.

PMID- 9027499
TI  - Genomic organization and expression of the human fatty aldehyde dehydrogenase
      gene (FALDH).
AB  - Mutations in the fatty aldehyde dehydrogenase (FALDH) gene cause Sjogren-Larsson
      syndrome (SLS)-a disease characterized by mental retardation, spasticity, and
      congenital ichthyosis. To facilitate mutation analysis in SLS and to study the
      pathogenesis of FALDH deficiency, we have determined the structural organization
      and characterized expression of the FALDH (proposed designation ALDH10) gene. The
      gene consists of 10 exons spanning about 30.5 kb. A TATA-less promoter is
      associated with the major transcription initiation site found to be 258 bp
      upstream of the ATG codon. The GC-rich sequences surrounding the transcription
      initiation site encompassed regulatory elements that interacted with proteins in
      HeLa nuclear extracts and were able to promote transcription in vitro. FALDH is
      widely expressed as three transcripts of 2, 3.8, and 4.0 kb, which originate from
      multiple polyadenylation signals in the 3' UTR. An alternatively spliced mRNA was
      detected that contains an extra exon and encodes an enzyme that is likely to have
      altered membrane-binding properties. The FALDH gene lies only 50-85 kb from
      ALDH3, an aldehyde dehydrogenase gene that has homologous sequence and
      intron/exon structure.

PMID- 9027500
TI  - Comparative mapping in the beige-satin region of mouse chromosome 13.
AB  - The proximal end of mouse chromosome (Chr) 13 contains regions conserved on human
      chromosomes 1q42-q44, 6p23-p21, and 7p22-p13. This region also contains mutations
      that may be models for human disease, including beige (human Chediak-Higashi
      syndrome). An interspecific backcross of SB/Le and Mus spretus mice was used to
      generate a molecular genetic linkage map of mouse chromosome 13 with an emphasis
      on the proximal region including beige (bg) and satin (sa). This map provides the
      gene order of the two phenotypic markers bg and sa relative to restriction
      fragment length polymorphisms and simple sequence length polymorphisms in 131
      backcross animals. In parallel, we have created a physical map of the region
      using Nidogen (Nid) as a molecular starting point for cloning a YAC contig that
      was used to identify the beige gene. The physical map provides the fine-structure
      order of genes and anonymous DNA fragments that was not resolved by the genetic
      linkage mapping. The results show that the bg region of mouse Chr 13 is highly
      conserved on human Chr 1q42-q44 and provide a starting point for a complete
      functional analysis of the entire bg-sa interval.

PMID- 9027501
TI  - Sequence analysis of 497 mouse brain ESTs expressed in the substantia nigra.
AB  - The use of subtracted, region-specific cDNA libraries combined with single-pass
      cDNA sequencing allows the discovery of novel genes and facilitates molecular
      description of the tissue or region involved. We report the sequence of 497 mouse
      expressed sequence tags (ESTs) from two subtracted libraries enriched for cDNAs
      expressed in the substantia nigra, a brain region with important roles in
      movement control and Parkinson disease. Of these, 238 ESTs give no database
      matches and therefore derive from novel genes. A further 115 ESTs show sequence
      similarity to ESTs from other organisms, which themselves do not yield any
      significant database matches to genes of known function. Fifty-six ESTs show
      sequence similarity to previously identified genes whose mouse homologues have
      not been reported. The total number of ESTs reported that are new for the mouse
      is 407, which, together with the 90 ESTs corresponding to known mouse genes or
      cDNAs, contributes to the molecular description of the substantia nigra.

PMID- 9027502
TI  - High-resolution linkage map in the proximity of the host resistance locus Cmv1.
AB  - The mouse chromosome 6 locus Cmv1 controls replication of mouse Cytomegalovirus
      (MCMV) in the spleen of the infected host. In our effort to clone Cmv1, we have
      constructed a high-resolution genetic linkage map in the proximity of the gene.
      For this, a total of 45 DNA markers corresponding to either cloned genes or
      microsatellites were mapped within a 7.9-cM interval overlapping the Cmv1 region.
      We have followed the cosegregation of these markers with respect to Cmv1 in a
      total of 2248 backcross mice from a preexisting interspecific backcross panel of
      281 (Mus spretus x C57BL/6J)F1 x C57BL/6J and 2 novel panels of 989 (A/ J x
      C57BL6)F1 x A/J and 978 (BALB/c x C57BL/6J)F1 x BALB/c segregating Cmv1. Combined
      pedigree analysis allowed us to determine the following gene order and intergene
      distances (in cM) on the distal region of mouse chromosome 6: D6Mit216-(1.9)
      D6Mit336-(2.2)- D6Mit218-(1.0)-D6Mit52-(0.5)-D6Mit194-(0.2)-Nkrp 1/
      D6Mit61/135/257/289/338-(0.4)-Cmv1/Ly49A/D6Mit370++ +- (0.3)
      Prp/Kap/D6Mit13/111/219-(0.3)-Tel/D6Mit374/290/ 220/196/195/110-(1.1)-D6Mit25.
      Therefore, the minimal genetic interval for Cmv1 of 0.7 cM is defined by 13
      tightly linked markers including 2 markers, Ly49A and D6Mit370, that did not show
      recombination with Cmv1 in 1967 meioses analyzed; the proximal limit of the Cmv1
      domain was defined by 8 crossovers between Nkrp1/ D6Mit61/135/257/289/338 and
      Cmv1/Ly49A/D6Mit370, and the distal limit was defined by 5 crossovers between
      Cmv1/Ly49A/D6Mit370 and Prp/Kap/D6Mit13/111/219. This work demonstrates tight
      linkage between Cmv1 and genes from the natural killer complex (NKC), such as
      Nkrp1 and Ly49A, suggesting that Cmv1 may represent an NK cell recognition
      structure encoded in the NKC region.

PMID- 9027503
TI  - Mapping of the locus for autosomal dominant amelogenesis imperfecta (AIH2) to a 4
      Mb YAC contig on chromosome 4q11-q21.
AB  - Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group
      of inherited enamel defects. We recently mapped a locus for autosomal dominant
      local hypoplastic amelogenesis imperfecta (AIH2) to the long arm of chromosome 4.
      The disease gene was localized to a 17.6-cM region between the markers D4S392 and
      D4S395. The albumin gene (ALB), located in the same interval, was a candidate
      gene for autosomal dominant AI (ADAI) since albumin has a potential role in
      enamel maturation. Here we describe refined mapping of the AIH2 locus and the
      construction of marker maps by radiation hybrid mapping and yeast artificial
      chromosome (YAC)-based sequence tagged site-content mapping. A radiation hybrid
      map consisting of 11 microsatellite markers in the 5-cM interval between D4S409
      and D4S1558 was constructed. Recombinant haplotypes in six Swedish ADAI families
      suggest that the disease gene is located in the interval between D4S2421 and ALB.
      ALB is therefore not likely to be the disease-causing gene. Affected members in
      all six families share the same allele haplotypes, indicating a common ancestral
      mutation in all families. The AIH2 critical region is less than 4 cM and spans a
      physical distance of approximately 4 Mb as judged from radiation hybrid maps. A
      YAC contig over the AIH2 critical region including several potential candidate
      genes was constructed.

PMID- 9027504
TI  - The human NTT gene: identification of a novel 17-kb noncoding nuclear RNA
      expressed in activated CD4+ T cells.
AB  - We describe the cloning and characterization of the NTT gene (noncoding
      transcript in T cells), identified by differential display RT-PCR based on the
      differential presence of its transcript in a subset of activated, human CD4+ T
      cell clones. The full-length cDNA and genomic sequences were cloned and found to
      produce a 17-kb transcript that is polyadenylated, but is not spliced. Consistent
      with the transcript's nuclear predominance, NTT has no open reading frame larger
      than 270 bp. It is transcribed in a select subset of CD4+ T-cell clones
      propagated in vitro. Its transcription can also be induced in freshly isolated T
      cells by in vitro activation with PHA or with PMA and ionomycin. In vivo, NTT
      transcripts are found only in activated, but not resting, T cells. Transcripts
      were absent in a variety of lymphoid cell lines and transformed lines from other
      tissues. NTT is a new member of the small group of genes including XIST (X
      specific transcript), H19, and IPW (imprinted gene in the Prader-Willi syndrome
      region), which are transcribed but not translated, and may have a role in the
      regulation of neighboring genes. XIST, H19, and IPW exhibit monoallelic
      expression, but both NTT alleles are expressed in CD4+ T-cell clones. Southern
      blot and fluorescence in situ hybridization analyses show that NTT is a single
      copy gene residing in chromosome 6q23-q24, near the interferon-gamma receptor
      gene (IFN-gamma R). Their proximity and shared expression pattern suggest a
      possible functional relationship.

PMID- 9027505
TI  - Toward cloning of a novel ataxia gene: refined assignment and physical map of the
      IOSCA locus (SCA8) on 10q24.
AB  - Infantile onset spinocerebellar ataxia (IOSCA) is a progressive neurological
      disorder of unknown etiology. It is inherited as an autosomal recessive trait and
      has so far been reported in just 19 Finnish patients in 13 separate families. We
      have previously assigned the IOSCA locus (HGMW-approved symbol SCA8) to
      chromosome 10q, where no previously identified ataxia loci are located. Haplotype
      analysis combined with genealogical data provided evidence that all the IOSCA
      cases in Finland originate from a single 30- to 40-generation-old founder
      mutation. By analyzing extended disease haplotypes observed today, the IOSCA
      locus can now be restricted to a region between two adjacent microsatellites,
      D10S192 and D10S1265, with no genetic intermarker distance. We have constructed a
      detailed physical map of this 270-kb IOSCA region and cytogenetically localized
      it to 10q24. We have also assigned two previously known genes, PAX2 and CYP17,
      more precisely into this region, but the sequence analysis of coding regions of
      these two genes has not revealed mutations in an IOSCA patient. The obtained long
      range clones will form the basis for the isolation of a novel ataxia gene.

PMID- 9027506
TI  - cDNA cloning, expression analysis, and chromosomal localization of a gene with
      high homology to wheat eIF-(iso)4F and mammalian eIF-4G.
AB  - A novel mammalian gene, Eif4g2, with a high degree of homology to the p82 subunit
      of the wheat germ eukaryotic translation initiation factor eIF-(iso)4F and
      mammalian eIF-4G has been isolated. Zoo blot analysis indicates that Eif4g2 is a
      single-copy gene that is highly conserved among vertebrates. Northern blot
      analysis shows that Eif4g2 is ubiquitously expressed at high levels in all human
      and mouse tissues examined. The 3810-nucleotide Eif4g2 cDNA contains a 907-amino
      acid open reading frame that codes for a polypeptide with a predicted molecular
      mass of 102 kDa. The Eif4g2 polypeptide exhibits an overall similarity to wheat
      p82 of 52%. A 248-amino-acid segment at the amino-terminal end of both peptides
      exhibits 63% similarity and contains conserved potential RNA binding domains and
      a phosphorylation site. The Eif4g2 polypeptide contains multiple potential N
      linked glycosylation sites as well as protein kinase C and casein kinase II
      phosphorylation sites. Southern blot analysis of DNA from interspecific backcross
      mice shows that Eif4g2 is localized to distal mouse chromosome 7 in a region
      syntenic with human chromosome 11p15.

PMID- 9027507
TI  - Cloning and characterization of Rep-8 (D8S2298E) in the human chromosome 8p11.2
      p12.
AB  - A novel human gene referred to as the Rep-8 gene (D8S2298E) was cloned by a
      combination of exon trapping, thermal asymmetric interlaced-PCR, and screening of
      a cDNA library. It is located in human chromosome 8p11.2-p12. The gene consists
      of eight exons and spans about 20 kb between the glutathione S-reductase and the
      protein phosphatase 2A beta subunit genes. The full-length Rep-8 gene contains
      1483 nucleotides and codes for a protein of 270 amino acids. Southern blot
      experiments showed that the Rep-8 gene exists as a single copy per haploid. With
      a zoo blot analysis, human Rep-8 DNA hybridized strongly with the monkey DNA, but
      only weakly with the DNAs of species other than Homo sapiens. Northern blot
      analysis showed that it is expressed abundantly in the testis and ovary,
      suggesting that the Rep-8 gene product may play a role in reproduction.

PMID- 9027509
TI  - Sequence analysis of two genomic regions containing the KIT and the FMS receptor
      tyrosine kinase genes.
AB  - The KIT and FMS tyrosine kinase receptors, which are implicated in the control of
      cell growth and differentiation, stem through duplications from a common
      ancestor. We have conducted a detailed structural analysis of the two loci
      containing the KIT and FMS genes. The sequence of the approximately 90-kb KIT
      locus reveals the position and size of the 21 introns and of the 5' regulatory
      region of the KIT gene. The introns and the 3'-untranslated parts of KIT and FMS
      have been analyzed in parallel. Comparison of the two sequences shows that, while
      introns of both genes have extensively diverged in size and sequence, this
      divergence is, at least in part, due to intron expansion through internal
      duplications, as suggested by the discrete extant analogies. Repetitive elements
      as well as exon predictions obtained using the GRAIL and GENEFINDER programs are
      described in detail. These programs led us to identify a novel gene, designated
      SMF, immediately downstream of FMS, in the opposite orientation. This finding
      emphasizes the gene-rich characteristic of this genomic region.

PMID- 9027508
TI  - Cloning and sequencing of the mouse Gli2 gene: localization to the Dominant
      hemimelia critical region.
AB  - The GLI family of zinc finger genes has been implicated in both neoplastic and
      developmental disorders. We have cloned and sequenced the mouse homolog of the
      zinc finger gene Gli2 and demonstrated significant similarity to the human GLI3
      gene. We have also localized Gli2 to mouse chromosome 1, in the vicinity of the
      morphogenetic mutation Dominant hemimelia (Dh), which is characterized by tibial
      hemimelia, poly/oligodactyly, and a number of visceral abnormalities, most
      strikingly absence of the spleen. Using a Gli2-associated microsatellite, we
      demonstrated no recombination between Dh and Gli2 in a Dh intraspecific
      backcross. Gli2 is expressed in Dh heterozygotes and homozygotes. However, using
      a combination of mismatch analysis and direct sequencing, we have failed to
      identify any mutations in the coding sequence of Gli2 from Dh. We have also
      demonstrated that it is unlikely that there are any Gli genes in the mouse genome
      in addition to the previously described Gli, Gli2, and Gli3.

PMID- 9027510
TI  - A physical map at 1p31 encompassing the acute insulin response locus and the
      leptin receptor.
AB  - Recently, we reported genetic linkage in Pima Indians between the acute insulin
      response to an intravenous glucose challenge and the short tandem repeat marker
      D1S198, indicative of a genetic element in this region that controls the
      phenotypic variation in the first phase of insulin secretion. As a first step to
      isolating the gene responsible for the acute insulin response, we have
      constructed a yeast artificial chromosome (YAC) contig map that spans the DNA
      microsatellites D1S438 through D1S464. The contig comprises 34 YACs on which we
      have mapped 44 ends of the genomic DNA inserts from the 34 YACs, 13 short tandem
      repeats, eight expressed sequence tags, and six genes. In addition, we have used
      this contig to construct a physical map encompassing approximately 9 Mb of DNA in
      this region.

PMID- 9027511
TI  - The cloning of a human ABC gene (ABC3) mapping to chromosome 16p13.3.
AB  - The ATP binding cassette (ABC) transporters, or traffic ATPases, constitute a
      large family of proteins responsible for the transport of a wide variety of
      substrates across cell membranes in both prokaryotic and eukaryotic cells. We
      describe a human ABC protein with regions of strong homology to the recently
      described murine ABC1 and ABC2 transporters. The gene for this novel protein,
      human ABC3, maps near the polycystic kidney disease type 1 (PKD1) gene on
      chromosome 16p13.3. The ABC3 gene is expressed at highest levels in lung compared
      to other tissues.

PMID- 9027512
TI  - Localization of the human gene for macrophage migration inhibitory factor (MIF)
      to chromosome 22q11.2.

PMID- 9027513
TI  - Basic methods for sensitivity analysis of biases.
AB  - BACKGROUND: Most discussions of statistical methods focus on accounting for
      measured confounders and random errors in the data-generating process. In
      observational epidemiology, however, controllable confounding and random error
      are sometimes only a fraction of the total error, and are rarely if ever the only
      important source of uncertainty. Potential biases due to unmeasured confounders,
      classification errors, and selection bias need to be addressed in any thorough
      discussion of study results. METHODS: This paper reviews basic methods for
      examining the sensitivity of study results to biases, with a focus on methods
      that can be implemented without computer programming. CONCLUSION: Sensitivity
      analysis is helpful in obtaining a realistic picture of the potential impact of
      biases.

PMID- 9027514
TI  - Cancer incidence among Icelandic pesticide users.
AB  - BACKGROUND: This study was done to examine the cancer risk among pesticide users
      in Iceland. METHODS: We have followed a cohort of 2449 licensed pesticide users,
      students from a horticultural college, members of a pension fund for market
      gardeners, horticulturists and vegetable farmers up until the end of 1993 in the
      Icelandic Cancer Registry of cancer incidence. The observed number of cancers was
      compared with expected values calculated on the basis of cancer incidence for
      males and females in Iceland. RESULTS: The standardized incidence ratio (SIR) for
      all cancer sites was 0.80. Among females the increased incidence for cancer of
      lymphatic and haematopoietic tissue was significant (SIR = 5.56, 95% confidence
      interval (CI) 1.12-16.23). The incidence of rectal cancer was three times that
      expected (SIR = 2.94, 95% CI: 1.07-6.40), and this cancer was even more
      predominant among the licensed pesticides users (SIR = 4.63, 95% CI: 1.49-10.80).
      All cancers of the rectum were adenocarcinoma, however, one was adenocarcinoma in
      villous adenoma and one adenocarcinoma in tubulo-villous adenoma. CONCLUSION: The
      results provide some support for the suggestion that pesticide exposure may lead
      to cancer of the lymphatic and haematopoietic tissue in females. We suggest that
      some of the pesticides to which the licensed pesticide users were exposed may
      lead to rectal cancer.

PMID- 9027515
TI  - Cancer in banana plantation workers in Costa Rica.
AB  - BACKGROUND: Costa Rica has population and disease registries with potential value
      for epidemiological research. Pesticides have been intensively used on banana
      plantations, for example dibromochloropropane (DBCP). This study was planned to
      examine the quality of the cancer and civil registries and the feasibility of
      record linkages, and to explore cancer patterns among a highly exposed group.
      METHODS: A retrospective cohort study was carried out. Workers on the payrolls of
      banana companies, as reported to the Social Security System at any time between
      1972 and 1979, were followed up in the cancer registry between 1981 and 1992: 29
      565 men and 4892 women for 407 468 person-years. The observed cases of cancer
      were compared to the expected values, derived from the national incidence rates.
      RESULTS: We identified 368 cancer cases, 292 among men (standardized incidence
      ratio [SIR] = 76, 95% confidence interval [CI] 67-84) and 76 among women (SIR =
      116, 95% CI: 90-142). Among men increased SIR were observed for melanoma (SIR =
      197, 95% CI: 94-362) and penile cancer (SIR = 149, 95% CI: 55-324); among women
      for cervix cancer (SIR = 182, 95% CI: 122-241) and leukaemia (SIR = 274, 95% CI:
      86-639). Risk estimates for lung cancer were evaluated among male workers with
      the longest time of employment. CONCLUSIONS: Follow-up was difficult due to
      deficient identification variables in the cancer registry and to easier
      identification of the living compared to the decreased in the civil registry at
      the end of the observation period. The various systematic errors in this study
      are likely to produce an underestimation of the relative risk estimates. This
      study contributes to improvements of the registries and increases the potential
      for cancer epidemiology in Costa Rica and other developing countries.

PMID- 9027516
TI  - Incidence of malignant melanoma of the skin in Norway, 1955-1989: associations
      with solar ultraviolet radiation, income and holidays abroad.
AB  - BACKGROUND: Norway has the highest incidence of melanoma in Europe. This study
      analyses geographical variations in melanoma incidence within Norway and their
      association with possible aetiological factors. METHODS: Data on melanoma
      incidence from the Norwegian Cancer Registry were used to calculate standardized
      incidence ratios (SIR) for the 19 counties in Norway for each 5-year period from
      1955 to 1989. Multiple regression analysis was used to examine the associations
      between these SIR and local UVB levels, holidays abroad and income. Similar
      methods were also used to analyse changes in SIR between 1955-1969 and 1985-1989.
      RESULTS: There was a highly significant association between melanoma incidence
      and UVB in each of the time periods studied. Income showed a significant positive
      association in the 1960s and early 1970s but not later. Foreign holidays showed a
      significant positive association in the 1980s, but not earlier. Changes in
      melanoma SIR between 1955-1969 and 1985-1989 were significantly positively
      associated with holidays abroad and negatively with income levels. CONCLUSIONS:
      Melanoma incidence in Norway is closely related to local levels of UVB radiation
      independently of other factors suggesting that local exposures carry significant
      risk. Risks would probably increase if ozone depletion led to enhanced UVB flux
      (estimated as 1.6% rise in incidence for each 1% increase in UVB). By the end of
      the study period income was no longer a significant factor but holidays abroad
      had started to have a detectable effect on melanoma incidence.

PMID- 9027517
TI  - Sojourn time, sensitivity and positive predictive value of mammography screening
      for breast cancer in women aged 40-49.
AB  - BACKGROUND: In mammographic screening for breast cancer in women aged 40-49,
      previous studies have found very low estimates of sensitivity and predictive
      value. Methods of estimation have, however, used primitive models with relatively
      strong assumptions and less than full use of the data. METHODS: Here we estimate
      the underlying preclinical incidence, mean sojourn time, sensitivity and positive
      predictive value by a variety of methods in a randomized trial of mammographic
      screening (The Swedish Two-County Trial) and a service screening programme (The
      Florence Programme, 1975-1986) in women aged 40-49 years. RESULTS: In the Two
      County study, sensitivity estimates ranged from 72-83% and predictive value from
      39-89%. In the Florence programme, sensitivity estimates ranged from 69-85% and
      predictive value was uniformly estimated as 100%. CONCLUSIONS: The methods
      involving more explicit modelling of the disease process and fewer assumptions
      tended to find higher estimates of predictive value in the Two-County study. The
      results suggest that previously poor sensitivity and predictive value estimates
      may have been overpessimistic.

PMID- 9027518
TI  - Lifestyle and risk of stomach cancer: a hospital-based case-control study.
AB  - BACKGROUND: Stomach cancer (SC) is the most frequent cancer among males and third
      most common cancer among females in Madras, India. The incidence rate of SC is
      higher in Southern India compared to Northern India. METHODS: A hospital-based
      case-control study on 388 incident cases of SC was carried out in Madras as part
      of a multicentre study in India to identify the risk factors for SC. Cases were
      matched to cancer controls based on age (+/- 5 years), sex, religion and mother
      tongue. Categorical variables for income group, level of education and area of
      residence were included in all models to control for confounding. RESULTS:
      Smokers had a twofold risk of SC (95% confidence interval [CI] = 1.25-3.78)
      compared to non smokers and the risk seen among current smokers (odds ratio [OR]
      = 2.5; 95% CI: 1.36-4.44) was significantly different from that seen among
      exsmokers (OR = 1.5; 95% CI: 0.67-3.54). The risk among those who smoke bidi (OR
      = 3.2; 95% CI: 1.80-5.67) was higher than that seen among cigarette (OR = 2.0;
      95% CI: 1.07-3.58) and chutta (OR = 2.4; 95% CI: 1.18-4.93) smokers. Significant
      dose response relationships were observed with age began smoking bidi (P < 0.001)
      and with lifetime exposure to bidi (P < 0.001), cigarette (P < 0.01) and chutta
      (P < 0.05) smoking. The habits of drinking alcohol and chewing did not emerge as
      risk factors. An interaction effect was not seen between the lifestyle habits.
      Attributable risk (AR) for smoking among exsmokers was 33% and current smokers
      60%. Population AR for smoking was 31%. CONCLUSION: Smoking tobacco is an
      independent risk factor for SC.

PMID- 9027519
TI  - Trends in mortality, incidence and case fatality of ischaemic heart disease in
      Denmark, 1982-1992.
AB  - BACKGROUND: In Denmark, as in many other Western countries, a decline in
      mortality from ischaemic heart disease (IHD) has been observed. The present study
      assesses whether the decline in IHD mortality is due to a decrease in incidence
      and/or case-fatality, and whether parallel changes occurred in the various
      manifestations of IHD requiring hospitalization. METHODS: The National Patient
      Register of hospital discharges and the Causes-of-Death Register were linked and
      all cases of first admission for IHD including AMI and fatal first manifestations
      of IHD since 1977 in the entire Danish population were identified. Cases of AMI
      and IHD were considered as incident cases if no admission for these diagnoses had
      occurred during the preceding 5 years. Sex-specific, age-standardized annual
      mortality, incidence and case-fatality rates of AMI (ICD8 code 410), narrowly
      defined IHD (NIHD, ICD8 codes 410-4) and broadly defined IHD (BIHD, ICD8 codes
      410-4, 427 and 795-6) were calculated for the period 1982-1992. RESULTS: During
      the entire period the age-standardized mortality of AMI, NIHD and BIHD decreased
      in both men and women. The incidence of AMI and NIHD decreased, while the
      incidence of BIHD remained constant. Case fatality of AMI decreased in both men
      and women, while case fatality of NIHD and BIHD decreased in men and in women
      aged 0-64 years only. CONCLUSION: The declining mortality from IHD in Denmark may
      be partly due to declining incidence as well as declining case fatality, but
      changes in disease manifestation or diagnostic drift may also contribute because
      more broadly defined diagnostic groups showed less or no decline in incidence.

PMID- 9027520
TI  - Development and tracking of central patterns of subcutaneous fat in adolescence
      and adulthood: the Amsterdam Growth and Health Study.
AB  - BACKGROUND: A central pattern of body fat is recognized as a risk indicator of
      cardiovascular diseases in adulthood. The development of this body fat pattern
      from childhood into adulthood however, remains to be explored. METHODS: The
      development of two trunk skinfolds (subscapular; supra-iliac), two extremity
      skinfolds (biceps; triceps), and three trunk-extremity skinfold ratios for males
      (n = 71) and females (n = 84), were described over a period of 17 years from 13
      to 29 years of age. In addition, tracking of the skinfolds and the skinfold
      ratios was investigated over this period. Data for this study came from the
      Amsterdam Growth and Health Study, an ongoing longitudinal study in the
      Netherlands that started in 1977. RESULTS: In adolescence, a decrease was seen in
      extremity skinfolds for men but not for women. For both sexes, the trunk
      skinfolds increased over the entire period of study. An increase was found in
      trunk-extremity skinfold ratios in males, but not in females. Tracking
      coefficients, calculated as Pearson correlation coefficients between the initial
      measurement and subsequent measurements, were about 0.4 for the single skinfolds
      between 13 and 29 years of age for both men and women. For the skinfold ratios,
      these correlation coefficients were about 0.55. Longitudinal tracking
      coefficients, measuring the association between the initial measurement and all
      follow-up data simultaneously, were about 0.65 for both men and women.
      CONCLUSIONS: A central pattern of body fat, mainly seen in males, seems to start
      in adolescence. From a preventive point of view, tracking coefficients were too
      low to be of predictive value. In order to conclude that the roots of a central
      pattern of body fat are in adolescence, careful search for determinants of change
      of this body fat pattern is needed.

PMID- 9027521
TI  - Incidence, natural history and cardiovascular events in symptomatic and
      asymptomatic peripheral arterial disease in the general population.
AB  - BACKGROUND: Intermittent claudication is associated with a poor prognosis, but
      less is known of the risks associated with asymptomatic peripheral arterial
      disease. The aims of this study were to determine the incidence and natural
      history of claudication, and the incidence of cardiovascular events in
      symptomatic and asymptomatic peripheral arterial disease. METHODS: In 1988, 1592
      subjects aged 55-74 years were selected randomly from the age-sex register of 10
      general practices in Edinburgh, Scotland. The presence of peripheral arterial
      disease was determined by the World Health Organization questionnaire on
      intermittent claudication, the ankle brachial pressure index and a reactive
      hyperaemia test. This cohort was followed prospectively over 5 years for
      subsequent cardiovascular events and death. RESULTS: One hundred and sixteen new
      cases of claudication were identified (incidence density 15.5 per 1000 person
      years). Of those with claudication at baseline, 28.8% and still had pain after 5
      years, 8.2% underwent vascular surgery or amputation, and 1.4% developed leg
      ulceration. Claudicants had a significantly increased risk of developing angina
      compared with normals (RR: 2.31, 95% CI: 1.04-5.10), and asymptomatic subjects
      had a slightly increased risk of myocardial infarction and stroke. Deaths from
      cardiovascular disease were more likely in both claudicants (RR: 2.67, 95% CI:
      1.34-5.29) and subjects with major (RR: 2.08, 95% CI: 1.13-3.83) or minor
      asymptomatic disease (RR: 1.74, 95% CI: 1.09-2.76). Subjects with major
      asymptomatic disease also had an increased risk of non-cardiovascular death (RR:
      2.19, 95% CI: 1.33-3.59), and therefore had the highest overall risk of death
      (RR: 2.44, 95% CI: 1.59-3.74). CONCLUSIONS: Subjects with asymptomatic peripheral
      arterial disease appear to have the same increased risk of cardiovascular events
      and death found in claudicants.

PMID- 9027522
TI  - Regular leisure time physical activity predicts high activity of tissue
      plasminogen activator: The Northern Sweden MONICA Study.
AB  - BACKGROUND: Leisure time physical activity protects against the development of
      cardiovascular disease, partly by lowering blood pressure, cholesterol and body
      weight. Little is known about the effects of regular exercise on fibrinolytic
      variables in the population. METHODS: In a population sample of 733 men and 774
      women aged 25-64 years physical activity during leisure time was related to
      fibrinolytic variables. RESULTS: The activity of tissue plasminogen activator
      (tPA) increased linearly with greater physical activity, the difference between
      sedentary and most active subjects being 28.9% in men and 11.6% in women. The tPA
      mass concentrations decreased by 27.4% and 28.0% in men and women respectively,
      as did also plasminogen activator inhibitor (PAl-1) activity; 38.5% and 30.6%.
      Tests for trend were significant (P < 0.001) for all but tPA activity in women.
      Adjusting for age, body mass index and waist:hip ratio only slightly decreased
      three relationships. When taking triglyceride into account, tPA activity and PAl
      1 activity (in men) were no longer significantly related to physical activity
      level but lower tPA mass concentrations and PA1-1 activity (in women) were still
      found in those who exercised regularly. Further adjustment for insulin levels
      abolished all differences, except for PA1-1 activity in women. CONCLUSION:
      Greater leisure time physical activity is associated with an increased
      fibrinolytic activity. This may contribute to less cardiovascular disease in
      subjects who exercise regularly.

PMID- 9027523
TI  - Influence of parental occupation on coronary heart disease risk factors in
      children. The Cardiovascular Risk in Young Finns Study.
AB  - BACKGROUND: The influence of parental occupation on selected coronary heart
      disease risk factors was studied in a cohort of Finnish children aged 9, 12 and
      15 years (n = 1211) as part of the Cardiovascular Risk in Young Finns Study in
      1986. METHODS: The relationships of parental occupation to serum lipid and
      apolipoprotein concentrations, blood pressure, obesity, smoking, physical
      activity, diet and birthweight were examined. The occupation of the parents was
      obtained by a questionnaire and classified as I: upper non-manual (22%), II:
      lower non-manual (26%), III: upper manual (32%), IV: lower manual (5%) and F:
      farmers (15%). RESULTS: Highest serum total and how density lipoprotein
      cholesterol concentrations were found in classes IV and F. Boys from class IV had
      7.1% higher total cholesterol concentrations compared to class I (4.98 mmol/l
      versus 4.65 mmol/l, P = 0.0033), whereas farmers' girls had 10.4% higher
      concentrations than girls from class III (5.31 mmol/l versus 4.81 mmol/l, P =
      0.0057). Blood pressure was related to parental occupation only in boys, and the
      values were highest in class F. Boys from class IV smoked most often, and they
      also had lowest values for physical activity index and highest obesity indices.
      Farmers' children consumed significantly more saturated fat and cholesterol than
      children from other classes. In boys, the percentage of subjects with a low
      birthweight (< or = 10th percentile) was smallest in class I and greatest in
      class IV (7.1% versus 20.7%, P = 0.0330). CONCLUSIONS: Socioeconomic status based
      on parental occupation is associated with several coronary heart disease risk
      factors already present in children. These differences should be taken into
      account in prevention programmes aimed at children at an increased risk for
      developing coronary heart disease as adults.

PMID- 9027524
TI  - Lower consumption of wine and fish as a possible explanation for higher ischaemic
      heart disease mortality in Spain's Mediterranean region.
AB  - BACKGROUND: There is an apparent paradox in the geographical distribution of
      ischaemic heart disease (IHD) mortality in Spain. The Mediterranean regions,
      those with the lowest consumption of total and saturated fats, register the
      highest mortality due to IHD. This paper seeks to explain this paradox by
      examining the provincial distribution of IHD mortality in Spain and their known
      risk factors, dietetic and non-dietetic. METHODS: The study was based on data
      aggregated by province. Mortality data were taken from official vital statistics,
      while data on diet and other lifestyle habits were obtained from representative,
      large-scale, sample-based population surveys. Correlation and multiple regression
      analyses were run on standardized IHD mortality ratios for the period 1983-1987
      and potential dietetic and non-dietetic determinants in 1989-1981. RESULTS:
      Intake of total lipids, saturated and polyunsaturated fatty acids, fish and wine
      were lower in Spain's southern and eastern provinces. Consumption of wine, fish,
      chicken, dairy products, vegetables and blond cigarettes, as well as
      unemployment, explained 53% of the variation in IHD mortality. Consumption of
      fish and wine alone exhibited a statistically significant relationship (P < 0.05)
      with IHD mortality. Moderate consumption of wine was negatively associated with
      IHD mortality, whereas heavy consumption patterns revealed a positive
      association. CONCLUSIONS: Based on correlation analyses of ecological data, lower
      consumption of wine and fish may explain the apparent paradox of higher IHD
      mortality in the presence of a lower intake of saturated fats in Spain's
      Mediterranean regions.

PMID- 9027525
TI  - Geographical distribution of endomyocardial fibrosis in south Kerala.
AB  - BACKGROUND: Endomyocardial fibrosis (EMF) is a chronic heart disease confined to
      a few geographically specific locations within 15 degrees of the equator. Several
      aetiological hypotheses exist, among them filarial infection, eosinophilia, and
      toxic effect of the monazite element cerium from the soil. This study attempts to
      find out whether the pattern of distribution of EMF in south Kerala in India is
      consistent with the geochemical hypothesis. METHODS: From hospital records we
      identified all patients from south Kerala who had a confirmed diagnosis of EMF
      during the period 1978-1994. Our controls were patients from the southern
      districts diagnosed to have rheumatic heart disease (RHD) during the same period.
      We traced their residence address to the administrative subunit of taluk, and
      plotted the distribution of patients with EMF and RHD for each taluk in south
      Kerala. The taluks were then grouped into areas of high (> 4/100,000), medium
      (2.01-4/100,000), and low (< or = 2/100,000) density in each case. RESULTS: We
      identified an area of high density of EMF comprising four taluks near the
      coastline situated within the districts of Alapuzha, Kollam, and Pathanamthitta.
      Two coastal taluks in Kollam and Alapuzha districts are known areas of deposits
      of monazite elements in the state. Geographical distribution is not related to
      prevalence of filariasis and eosinophilia. CONCLUSION: Coexistence of high
      density of occurrence of EMF and deposits of monazite elements support the
      geochemical hypothesis.

PMID- 9027526
TI  - The relationship between body weight and patterns of smoking in women and men.
AB  - BACKGROUND: In the scientific literature, studies of the relationship between
      cigarette smoking and body weight yield conflicting results. Weight-lowering
      effects in women and men have been associated with smoking, however, no effects
      on weight have been proven. The purpose of this study was to examine the gender
      related association between cigarette smoking and relative weight in a rural
      population in Styria, Austria. METHODS: A database from a health survey conducted
      between 1989 and 1993 in 79 selected rural communities of Styria was used for
      these analyses. The sample consisted of 27,344 participants, 16,185 women and
      11,159 men, aged > or = 15 years. We controlled for possible confounding factors
      such as age, years of education, alcohol consumption, regular physical activity,
      and chronic diseases. RESULTS: For women and men, in comparison to non- and ex
      smokers, smoking is significantly correlated with lower body mass index (BMI). In
      contrast, heavy smoking and smoking cessation are significantly associated with
      higher relative weight. CONCLUSIONS: We found significant results confirming an
      association between cigarette smoking and lower BMI in women and men, whereas
      heavy smoking as well as smoking cessation were significantly correlated with
      higher relative weight. Health intervention programmes to quit smoking should
      take into account the underlying perceived benefits of smoking with regard to
      weight, especially its gender specificity.

PMID- 9027527
TI  - Association of respiratory symptoms with serum protease inhibitors and albumin
      levels in Japanese children.
AB  - BACKGROUND: Some individuals are more susceptible than others to the effects of
      environmental factors, although the physiological reasons for this are unknown.
      This study investigates the fundamental association between some serum proteins
      and respiratory symptoms in Japanese children. METHODS: The serum alpha 1
      antitrypsin (alpha 1AT), alpha 2-macroglobulin (alpha 2MG), and albumin
      concentrations were determined in 480 schoolchildren living in an area with low
      air pollution levels. Their respiratory symptoms were assessed from responses to
      questionnaires. RESULTS: Serum alpha 1AT levels were significantly lower in
      children with histories of allergic diseases, while their alpha 2MG levels were
      increased. Serum albumin levels were significantly decreased in children with
      asthma compared with those without, and the levels did not differ significantly
      for those children with wheezing symptoms or histories of allergic diseases.
      Serum alpha 1AT levels were only significantly lower in girls with asthma.
      Fourteen children (2.9%) were found to have decreased alpha 1AT levels of < 160
      mg/dl. All of these children had histories of allergic diseases, and the
      prevalence of asthma was remarkably higher in these children. Children with only
      wheezing symptoms showed no significant changes in serum alpha 1AT, alpha 2MG, or
      albumin levels. CONCLUSIONS: These findings suggest that serum alpha 1AT, alpha
      2MG, and albumin levels are associated with respiratory and allergic diseases in
      children. A decreased alpha 1AT level should be considered as a biological risk
      marker for these diseases.

PMID- 9027528
TI  - Air pollution and mortality in East Berlin during the winters of 1981-1989.
AB  - BACKGROUND: The relationship between air pollution and mortality in East Berlin
      was examined for the winters of 1981-1989. METHODS: Regression analysis included
      daily mean levels of sulphur dioxide (SO2) and suspended particulates (SP), and
      was controlled for temperature, humidity, week-day, month, and year. Moving
      averages of previous pollution were also used. RESULTS: Each pollutant was a
      significant contributor to excess mortality. The strongest association was found
      for mortality lagged for 2 days, which depended significantly on the level of SP
      (beta for in SP = 0.876; P = 0.008) and SO2 (beta for in SO2 = 0.635; P = 0.012),
      when regressed separately. When omitting days with pollutant concentrations above
      150 micrograms m-3, the pollutant-mortality relationship was linear, and a 100
      micrograms m-3 increase was associated with a 6.1% (SP) and 4.5% (SO2) mortality
      increase 2 days later, when pollutants were considered separately; this was
      reduced to 4.6% (SP) and 2.8% (SO2) increase, when both were considered
      simultaneously. CONCLUSIONS: The results show that short-term associations
      between air pollutants and mortality in East Berlin did exist during the winters
      1981-1989. Since the coefficients for SP and SO2 dropped when controlling for the
      other pollutant species, a similar strength of association with mortality for
      both pollutants was found.

PMID- 9027529
TI  - Asthma presentations to emergency departments in western Sydney during the
      January 1994 Bushfires.
AB  - BACKGROUND: From 5 to 12 January 1994, the state of New South Wales suffered from
      the worst bushfires seen this century. High levels of particulate air pollution
      were recorded in western Sydney from 7 to 14 January 1994, with nephelometry
      readings reaching 10.24 beta scat (10(-4)/m) and particulate matter < 10 mu
      readings peaking at 250.00 micrograms/m3. The aim of this study was to determine
      whether there was an increase in the proportion of asthma presentations to
      emergency departments (ED) in western Sydney as a result of the bushfire
      generated particulate air pollution. METHOD: We retrospectively analysed the
      emergency room attendance books for asthma presentations from seven public
      hospitals serving the Western Sydney and Wentworth Health Areas over two 6-7 week
      periods, 17 December 1992 to 31 January 1993, and 17 December 1993 to 31 January
      1994. Air pollution and meteorological data were obtained from local monitoring
      stations. RESULTS: The difference in the proportion of all ED presentations that
      were due to asthma during the week of the bushfire-generated air pollution,
      compared with the same week 12 months before, after adjusting for baseline
      changes over the 12-month period, was 0.0067 (95% CI: -0.0007, 0.0141). The
      maximum daily nephelometry reading was not a significant predictor of the daily
      number of asthma presentations to ED in any of the Poisson regression models.
      CONCLUSIONS: The bushfire-generated particulate air pollution in January 1994 did
      not result in an increase in asthma presentations to ED in western Sydney.

PMID- 9027530
TI  - Influence of occupational accidents and deaths related to lifestyle on mortality
      among merchant seafarers.
AB  - OBJECTIVES: The aim of the present historical cohort study was to enhance the
      understanding of the unusual mortality pattern seen among seafarers. The main
      object was to describe the mortality pattern of Danish seafarers in recent years
      with special reference to the influence of accidents in the maritime workplace
      and ashore and the influence of diseases related to lifestyle. SUBJECTS: A cohort
      of 24,132 male seafarers of all job categories employed on a Danish merchant ship
      between 1986 and 1993, was followed up. Mortality among those who left the
      occupation before the end of the follow-up period was analysed separately.
      RESULTS: The standardized mortality ratio was 1.43 (95% CI: 1.33-1.54) from all
      causes and 3.05 (95% CI: 2.62-3.52) from accidents. An excess mortality from
      natural causes was attributable mostly to an excess among deck and engine room
      crew and was mainly caused by diseases related to lifestyle. While active as
      seafarers, the SMR for accidents was 2.62 (95% CI: 2.12-3.20), accidents at the
      workplace explaining almost half the deaths. Among those who left shipping, the
      risk of fatal accidents increased. All categories of seafarers continued to have
      a high risk of fatal accidents into older age. CONCLUSION: Merchant seafarers
      were shown to have a higher mortality than the general population. Despite a very
      high risk of fatal accidents in the workplace, these accidents could only explain
      a proportion of the observed excess mortality. Accidents ashore and diseases
      related to lifestyle factors such as drinking and smoking made a major
      contribution to the observed excess mortality. The results indicate that people
      in occupations with a high risk of fatal accidents at the workplace also seem to
      have a high risk of accidents away from the workplace after leaving the
      occupation. The high risk lifestyle seems to be linked to lifestyle in general
      and hence the related diseases and high risk of death.

PMID- 9027531
TI  - Religious affiliation and all-cause mortality: a prospective population study in
      middle-aged men in eastern Finland.
AB  - BACKGROUND: Previous data suggest a favourable association between religion and
      mortality. METHODS: We investigated the association between selected religious
      groups and all-cause mortality in 1627 eastern Finnish men aged 42-60 years
      during 1984-1989 as a part of the Kuopio Ischaemic Heart Disease Risk Factor
      Study (KIHD). RESULTS: Eastern Orthodox men had a 5.1-fold (95% confidence
      interval [Cl: 1.98-13.3, P < 0.001) mortality as compared with Lutheran men after
      adjusting for main confounders. Adjustment for different sets of covariates did
      not affect the magnitude of relative hazard (RH) notably. Adjusted for the
      examination year, age, family history of coronary heart disease (CHD), and
      ischaemia in exercise electrocardiograms, RH was 4.4 (95% CI: 2.5-7.5, P < 0.001)
      and 4.7 (95% CI: 2.7-8.3, P < 0.001) after an additional adjustment for serum
      cholesterol, blood leucocytes, plasma fibrinogen, serum triglycerides, maximal
      oxygen uptake, height, and weight. With adjustment for income, childhood
      socioeconomic status (SES), and years of education RH for the Orthodox religion
      was 4.2 (95% CI: 2.4-7.3, P < 0.001) and 4.4 (95% CI: 2.5-7.7; P < 0.001) with
      depression, helplessness, quality of relationships, marital status and
      organizational participation, and 4.1 (95% CI: 2.4-7.2, P < 0.001) when adjusted
      for the use of tobacco and alcohol and the intensity of physical activity. After
      adjustment for migration because of the war the RH was 4.5 (95% CI: 1.9-10.8, P <
      0.001). CONCLUSIONS: Our findings indicate that mortality risk varies
      substantially by religious affiliation, and this variation cannot be attributed
      to differences in measures for a wide variety of health, behavioural,
      socioeconomic, biological, social, and other characteristics.

PMID- 9027532
TI  - Mortality during 25 years of follow-up of a cohort with diabetes.
AB  - BACKGROUND: Diabetes is one of the most common chronic diseases in Western
      populations. There have been few large published cohort studies of people with
      diabetes that have had more than 10 years of follow-up, and none other than the
      present one are in the UK. Such studies are important to understand the long-term
      fatal consequences of diabetes and their variation over time and between
      countries. METHODS: Cause-specific mortality was analysed in follow-up from 1966
      1970 to December 1992 of 5783 members of the British Diabetic Association living
      in England and Wales during 1966-1970. Comparison was made with age-, sex- and
      calendar year-specific mortality by cause in the general population of England
      and Wales. RESULTS: During the follow-up 3399 (58.8%) subjects died. The relative
      risk of all-cause mortality in the cohort compared to the general population was
      2.31 in women and 1.58 in men (both P < 0.001).Relative risks were greater for
      women than men at almost all ages and for each major diabetes-related cause of
      death. Absolute excess ('attributable') mortality rates were also greater in
      women than in men, except at ages < 50. Half the deaths in each sex were from
      circulatory diseases and only 3.4% were from renal disease. The relative risks of
      mortality for all-causes and circulatory diseases were particularly great at
      younger ages, but changed little with duration of follow-up. At ages < 40 the
      relative risks for all-causes were 3.75 in men and 5.51 in women and for
      ischaemic heart disease were 10.44 and 25.25 respectively (all P < 0.001). At
      these ages one-third of deaths were due to acute complications of diabetes,
      suicides and accidents, whereas at older ages these accounted for only 4% of
      deaths. CONCLUSIONS: The mortality rates at young ages in the cohort were around
      twice those in Sweden, Norway and Israel, suggesting that many of the deaths in
      England and Wales are preventable. The results also indicate a particular need
      for investigation and amelioration of cardiovascular risk factors in English and
      Welsh patients, especially women.

PMID- 9027533
TI  - Iron deficiency and anaemia in children with a high prevalence of
      haemoglobinopathies: implications for screening.
AB  - BACKGROUND: Haemoglobin (Hb) concentration is used as a sole test for iron
      deficiency anaemia (IDA) in most developing countries since most anaemia is
      believed to be due to iron deficiency and confirmatory testing is generally
      unavailable. Yet the validity of this approach in regions where
      haemoglobinopathies are endemic has not been documented. METHODS: Haemoglobin and
      serum ferritin (SF) were measured in 559 Northern Thai children aged 6 months to
      13 years of age. The sensitivity of SF to identify iron deficiency was also
      assessed in a subsample of children with low or low-normal Hb and normal SF by
      testing the Hb response to a trial of oral iron. RESULTS: While anaemia was
      common (27%), IDA constituted 19% and none of all anaemia in preschool and school
      age children, respectively (P < 0.002). Iron depletion was similarly more
      prevalent in younger children (P < 0.002). Children with IDA were younger (P <
      0.001) and the anaemia more severe (P < 0.0001) compared to those with non-IDA.
      Of anaemic children with normal SF values who received a therapeutic trial of
      iron, only 6% responded with an increase in Hb of > or = 1 g/dl. CONCLUSIONS: For
      populations such as ours most anaemia is not due to iron deficiency and a single
      Hb determination is therefore not acceptable for a presumptive diagnosis of IDA.

PMID- 9027534
TI  - The lack of selection bias in a snowball sampled case-control study on drug
      abuse.
AB  - BACKGROUND: Friend controls in matched case-control studies can be a potential
      source of bias based on the assumption that friends are more likely to share
      exposure factors. This study evaluates the role of selection bias in a case
      control study that used the snowball sampling method based on friendship for the
      selection of cases and controls. METHODS: The cases selected fro the study were
      drug abusers located in the community. Exposure was defined by the presence of at
      least one psychiatric diagnosis. Psychiatric and drug abuse/dependence diagnoses
      were made according to the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-III-R) criteria. Cases and controls were matched on sex, age and friendship.
      The measurement of selection bias was made through the comparison of the
      proportion of exposed controls selected by exposed cases (p1) with the proportion
      of exposed controls selected by unexposed cases (p2). If p1 = p2 then, selection
      bias should not occur. RESULTS: The observed distribution of the 185 matched
      pairs having at least one psychiatric disorder showed a p1 value of 0.52 and a p2
      value of 0.51, indicating no selection bias in this study. CONCLUSIONS: Our
      findings support the idea that the use of friend controls can produce a valid
      basis for a case-control study.

PMID- 9027535
TI  - Hepatitis A in a Chinese urban population: the spectrum of social and behavioural
      risk factors.
AB  - BACKGROUND: Viral hepatitis is a major public health problem in China. Hepatitis
      A infections represent a substantial proportion of these, particularly in urban
      centres. Little is known about the social and behavioural factors in the urban
      household environment that influence the transmission of hepatitis A. METHODS: We
      conducted a register-based case-control study to investigate the risk factor
      patterns for hepatitis A in the general population of the City of Wuhan, in the
      PR China. Cases were selected from district-based health registers. One control,
      matched for sex and age, was identified from the case's neighbourhood. Home-based
      interviews combined with household observation were performed to obtain
      information on social, behavioural and economic risk factors and the household's
      indoor and outdoor environment. Analysis included conditional logistic
      regression. RESULTS: Hepatitis A infection was associated with a variety of
      social and household-related factors, like handwashing habits (after working in
      the garden: adjusted odds ratio [OR] = 8.24, 95% confidence interval [CI]: 1.5
      44.2, before food preparation: OR = 4.68, 95% CI: 1.8-12.0; before eating: OR =
      4.92, 95% CI: 1.5-15.7), and the source of fresh vegetables (OR = 3.90, 95% CI:
      1.6-9.8). Hygiene in the kitchen and the household surroundings and the disposal
      of children's stools in vegetable gardens or refuse pits were significantly
      associated with univariate analysis only. The lack of possession of luxury
      consumer items as a surrogate indicator for income was significantly associated
      with the disease (OR = 2.47, 95% CI: 1.0-6.1). The study clearly established that
      exposure to health and hygiene education was less in the group of hepatitis A
      cases when compared to healthy controls (OR = 2.80, 95% CI: 0.9-8.3). CONCLUSION:
      The results of this study underline how social and behavioural factors are
      important determinants for hepatitis A in urban Chinese populations. These issues
      could be addressed by appropriate health and hygiene education targeted at high
      risk groups, and by strengthening existing procedures for monitoring and control
      of food hygiene.

PMID- 9027536
TI  - Risk factors for invasive Haemophilus influenzae disease among children 2-16
      years of age in the vaccine era, Switzerland 1991-1993. The Swiss H. Influenzae
      Study Group.
AB  - BACKGROUND: Continued surveillance, and detailed investigation of direct and
      indirect effects of conjugated vaccines and risk factors for invasive
      H.influenzae serotype B (Hib) disease in the vaccine era are important. METHODS:
      143 cases with invasive disease between 1991 and 1993 aged 2-16 years were
      selected retrospectively from a large incidence trend study. Controls (n = 336)
      were recruited from local vital registries and matched to cases for age, gender,
      and residence. Hib vaccination histories among study subjects and their siblings
      and other sociodemographic variables were obtained by questionnaires completed by
      the parents of these children. Adjusted odds ratio (OR) estimates were calculated
      by conditional logistic regression analysis. RESULTS: Most vaccinated subjects
      had received the Polysaccharide-Diphtheria Toxoid vaccine and estimated vaccine
      efficacy was high (95%; 95% confidence interval [CI] 60-99%). Also, the results
      suggested that protection afforded by vaccination against Hib extended to the
      family members of vaccinated children. School attendance was found to be
      protective against invasive Hib disease (OR:0.33; CI:1.2-14.4). Cases more often
      than controls reported suffering from asthma and allergies (OR:4.8; CI:1.2-19.4).
      CONCLUSIONS: Post-licensure vaccine efficacy is high among children > or = 2
      years of age. The observed association between asthma and epiglottitis is novel
      and deserves further investigation.

PMID- 9027537
TI  - The role of surveillance in a 'high risk' approach to the elimination of neonatal
      tetanus in Egypt.
AB  - BACKGROUND: Despite an international resolution to eliminate neonatal tetanus
      (NT) as a public health problem by the year 1995, 490000 cases occurred worldwide
      in 1994. An analysis of the NT elimination programme in Egypt was conducted to
      determine the utility of a 'high risk' approach in controlling this disease.
      METHODS: Three of the indicators for identifying districts at high risk of NT
      were evaluated. NT rates, tetanus toxoid coverage (TT2+), and urban or rural
      status. The reduction in NT incidence from 1992 to 1994 was compared between
      those high risk districts (> or = 1 NT case/1000 live births in 1992) which did
      or did not conduct supplementary immunization (P = 0.035). RESULTS: In a
      multivariate analysis, the strongest indicator of the NT risk in a district was
      the presence of > or = 1 case/1000 live births in the previous year (Rate ratios
      [RR] = 3.34 in 1993 and 3.07 in 1994, P < 0.001). The TT2+ coverage was not a
      reliable indicator of NT risk. Urban areas had a significantly lower risk than
      rural areas (RR = 0.62) in 1993 and 0.49 in 1994, P < 0.001). The decline in NT
      rates was greatest in the 'high risk' districts that conducted supplementary
      immunization in both 1993 and 1994. CONCLUSIONS: Although tetanus toxoid
      immunization of pregnant women will protect newborns from NT, TT2+ coverage
      calculated by the administrative method may not reflect a population's risk of
      NT. Surveillance data, however, can be used to identify areas where the ongoing
      risk NT is high. Conducting supplementary immunization in areas that are
      identified as 'high risk' on the basis of previous NT rates can significantly
      reduce the number of cases in subsequent years.

PMID- 9027540
TI  - International Consensus Group on Physical Activity Measurement.

PMID- 9027539
TI  - Whooping cough and Parkinson's disease. The Europarkinson Preparatory Activity
      Research Group.
AB  - BACKGROUND: We reported high levodopa use and prevalences of Parkinson's Disease
      (PD) in periodically, time-clustered, icelandic cohorts born after major whooping
      cough epidemics (MWCE). METHODS: In order to quantify a possible relationship
      between age at first post-birth MWCE and risk of PD we: 1) calculated cumulative
      incidences of PD during the period 1954-1963 in one-year Icelandic cohorts born
      between 1869 and 1927, using raw material from a reported survey; 2) identified
      MWCE from 1869 onwards in Iceland; 3) estimated cohort ages at onset of incidence
      period and at first MWCE; and 4) combined the above-mentioned information using
      log-linear models. In addition, we studied the prevalence of levodopa users in
      Icelandic birth cohorts during a recent period. RESULTS: The curves of the above
      mentioned incidences and prevalences in one-year birth-cohorts showed: 1) a
      similar, age-related, inverted V profile; and 2) a systematic notchy pattern,
      with peak values for one or both measurements for cohorts born during or after
      each of nine MWCE identified during the period 1869-1927. When 13 cohorts born in
      years with MWCE were excluded from the analysis, the risk of PD rose with age at
      first defined MWCE, with the linear increase being 8.4% per year (95% CI: -0.1
      18.3%). CONCLUSIONS: These results are consistent with reported effects of age at
      exposure in animal models of toxic parkinsonism, age-related changes in the
      dopamine receptor-GPT-binding protein-adenylatecyclase system observed in rats
      treated with pertussis toxin, and some PD epidemiological features. They suggest
      that pertussis neurotoxicity could be casually treated to PD worldwide.

PMID- 9027538
TI  - Urban schistosomiasis: morbidity, sociodemographic characteristics and water
      contact patterns predictive of infection.
AB  - BACKGROUND: Schistosomiasis (Schistosoma mansoni) is classically described as a
      rural disease that occurs in areas with poor sanitary conditions. This cross
      sectional study was undertaken in a suburban area of a large industrialized city
      in Brazil (Belo Horizonte), aiming at examining epidemiological characteristics
      of schistosomiasis in an urban setting. METHODS: A simple random sample of
      658/1896 dwellings was selected and 3049/3290 (92.7%) residents were submitted to
      stool examination. Of 518 eligible infected cases and 518 uninfected controls,
      87.1% and 89.9% participated in the study, respectively. RESULTS: The prevalence
      of S. mansoni infection was 20%, predominantly low egg counts in stools; no cases
      of splenomegaly were found. Signs and symptoms associated with infection were
      bloody stools (odds ratio [OR] = 8.0) and hardened palpable liver at the middle
      clavicular and at the middle sternal life (OR = 5.5 and 8.0 respectively).
      Sociodemographic variables and water contacts predictive of infection were age
      (10-19 and > or = 20 yrs; OR = 7.1 and 3.3, respectively), gender (male; OR =
      3.1), contacts for swimming and/or playing (twice a month or less and more than
      twice a month; OR = 2.2 and 3.0, respectively) and residence in Belo Horizonte
      (born in the City; OR = 2.5). Ninety per cent of dwellings had a piped water
      supply; no association between water supply and infection was found. CONCLUSION:
      Our results emphasize the need for schistosomiasis control measures focusing on
      water contacts for leisure purposes in this industrialized urban area.

PMID- 9027541
TI  - Influence of wholesale lamb marketing options and merchandising styles on retail
      yield and fabrication time.
AB  - Lamb carcasses (n = 94) from five packing plants, selected to vary in weight
      class and fat thickness, were used to determine retail yield and labor
      requirements of wholesale lamb fabrication. Carcasses were allotted randomly
      according to weight class to be fabricated as whole carcasses (n = 20), three
      piece boxes (n = 22), or subprimals (n = 52). Processing times (seconds) were
      recorded and wholesale and retail weights (kilograms) were obtained to calculate
      retail yield. Subprimals were fabricated into bone-in retail cuts or boneless or
      semi-boneless retail cuts. Retail yield for subprimal lamb legs decreased from
      85.3 +/- .6% for bone-in to 68.0 +/- .7% for a completely boneless retail
      product. Correspondingly, processing times increased from 126.1 +/- 5.4 s to
      542.0 +/- 19.2 s for bone-in and boneless legs, respectively. For all subprimals,
      retail yield percentage tended to decrease and total processing time increase as
      cuts were fabricated to boneless or semi-boneless end points compared with a bone
      in end point. Percentage retail yield did not differ (P > .05) among whole
      carcass, three-piece box, and subprimal marketing methods. Total processing time
      was shorter for subprimals (P < .05) than for the other two marketing methods.

PMID- 9027543
TI  - Phenotypic characterization of rambouillet sheep expressing the callipyge gene:
      I. Inheritance of the condition and production characteristics.
AB  - The objectives of this study were to determine the model of inheritance of the
      callipyge gene and to evaluate the growth, ADFI, feed efficiency, reproductive
      performance, and wool growth of sheep that are heterozygous for the callipyge
      gene. Ewes (n = 236) with a normal muscle phenotype and genotype were mated to
      three heterozygous rams that expressed the callipyge gene. Lambs (n = 311) were
      subjectively classified at weaning (90 to 120d) according to muscle phenotype by
      a panel of three evaluators working independently. The callipyge muscle phenotype
      was expressed in 150 lambs, whereas 161 lambs expressed a normal muscle
      phenotype. The percentage of lambs expressing the callipyge muscle phenotype
      (48.2%) did not differ (P > .1) from the expected 50%. Growth rate was similar
      for lambs of both phenotypes regardless of sex. Feed efficiency was superior (P <
      .05) for both male and female lambs with the callipyge muscle phenotype. Average
      daily feed intake was lower for male (P < .02) and female (P < .004) lambs with
      the callipyge muscle phenotype. Grease fleece weight and staple length at 12 mo
      were superior (P < .03) for ewes with a normal muscle phenotype. These results
      indicate that the callipyge gene in sheep is dominant when inherited from the
      paternal parent and lambs expressing the callipyge gene have increased feed
      efficiency and reduced ADFL.

PMID- 9027542
TI  - Biceps femoris and rump fat as additional ultrasound measurements for predicting
      retail product and trimmable fat in beef carcasses.
AB  - One hundred ninety-eight steers of Angus and Hereford breeding were evaluated
      ultrasonically for fat thickness over the 12-13th rib (UFAT), fat thickness over
      the rump (URUMP), 12-13th longissimus muscle area (UREA), and depth of the biceps
      femoris (UROUND) before slaughter. Carcass measurements associated with the USDA
      yield grade were also obtained. Carcasses were fabricated into closely trimmed
      (.32 cm fat), boneless subprimals. Regression procedures were used to predict
      weight and the percentages of retail product and trimmable fat. Final weight
      (FINALWT) accounted for most of the variation when predicting kilograms of retail
      product and trimmable fat, with R2 values of .836 and .435, respectively. As
      single predictors URUMP and UFAT accounted for most of the variation when
      predicting the percentages of retail product and trimmable fat with R2 values of
      .244 and .220, respectively. Adding URUMP to equations that included FINALWT,
      UREA, and UFAT increased R2 values for percentage of retail product from .175 to
      .318 and for weight of retail product from .847 to .865, whereas the addition of
      UROUND did not appreciably increase R2 values for the same models. Adding URUMP
      and UROUND to the model of FINALWT, UREA, and UFAT to predict kilograms and the
      percentage of trimmable fat increased R2 values from .530 to .610 and from .254
      to .360, respectively. Models using live-animal measurements to predict weight
      and the percentage of retail product gave R2 values equal to models using the
      actual measurements found in the USDA Yield Grade equation.

PMID- 9027545
TI  - Wind protection effects and airflow patterns in outside feedlots.
AB  - Steers were finished in three different sets of outside lots: 1) pens with
      overhead shelter on the north side; 2) pens south and southeast of a shelterbelt;
      and 3) pens with no shelter or windbreak. In trials conducted over a 3-yr period
      with predominantly British and British x Continental crossbred yearlings,
      performance improvements due to providing shelter or wind protection in the
      winter were not detected; however, in the summer, providing wind protection or
      shelter resulted in decreased (P < .10) cattle gains. Cattle fed in the
      unprotected area had greater (P < .05) fat thickness in the winter and greater
      marbling scores in the winter (P < .05) and autumn (P < .10) than cattle fed in
      protected areas. When averaged across facilities, season effects were detected
      for DMI (autumn > summer > winter > spring; P < .05). Feed:gain ratios followed a
      similar trend among seasons (summer and autumn > winter > spring P < .05). As a
      percentage of BW, winter (2.21), spring (2.19), and summer (2.18) DMI were less
      (P < .05) than autumn (2.35) DMI. Wind velocity data indicated that greater air
      flows tends to be found on mounds and less at the feedbunk in pens protected by
      shelterbelts. In unprotected, unsheltered pens, the greater airflow tends to be
      at the highest point in the pen (bunks and mounds). In Nebraska, benefits
      realized from feeding cattle in sheltered or protected areas under average or
      slightly milder than average winter weather conditions may be offset by lower
      performance experienced by cattle fed in those same areas in the summer. In
      addition, fat deposition seems to be enhanced in cattle exposed to moderate cold
      stress.

PMID- 9027544
TI  - Clostridial vaccination efficacy on stimulating and maintaining an immune
      response in beef cows and calves.
AB  - Experiments were conducted to determine the efficacy in stimulating and
      maintaining an immune response in the presence of maternal antibodies, compare
      the extent of the anamnestic responses to revaccination, and compare the maternal
      antibody response of 2- or 5-mL clostridial vaccination. In Exp. 1, 118 nursing
      calves were randomly assigned to receive a 2-mL (Alpha-7, A7) or a 5-mL
      clostridial vaccine (Ultrabac 7; UB7) at 50.4 +/- 15.30 (X +/- SD) d of age (d 0
      = date of calving). Calves were revaccinated with the same treatment on d 170.
      Blood samples were collected from 10 calves of each treatment group on d 50, 170,
      and 191 to determine antitoxin units for Clostridium perfringens type C (PC) and
      D (PD) and agglutination titers for Cl. chauvoei (CC). The A7-treated calves
      tended (P < .10) to have higher PC units on d 170, an increased rate of change in
      PD units from d 170 to d 191 (P < .06), and a tendency (P < .10) for enhanced CC
      titers on d 191 compared with UB7-treated calves. In Exp. 2, 109 pregnant cows
      and 83 pregnant heifers were randomly assigned within a 2 x 2 x 2 factorial
      design. The main effects were dam age (cow or heifer), dam treatment (A7 or UB7),
      and calf treatment (A7 or UB7). Dams were vaccinated with A7 or UB7 d 124
      prepartum (d -124) and d 53 after birth. At d 53.4 +/- 12.88, calves were
      vaccinated with A7 or UB7 (d 53). Calves were revaccinated with the same
      treatment on d 173. Blood samples were collected from 10 dams per treatment group
      on d -124, 53, and 173 and from their calves on d 53, 173, and 194. Cows had
      higher antitoxin levels for PC (P < .01) and PD (P < .05) than heifers. The A7
      treated dams had higher (P < .01) PD units on d 53 and d 173 and CC on d 173 than
      did UB7-treated dams. Calves from A7-treated cows had higher (P < .03) PD units
      on d 53 than calves from UB7-treated cows. The A7-treated calves had higher
      titers for CC (P < .01) on d 173 than did UB7-treated calves, and this enhanced
      level seemed to continue to d 194 (P < .08). In conclusion, titers for
      clostridial diseases in 50- to 53-d-old calves can be enhanced if dams are
      vaccinated approximately 4 mo before calving, and 120 d between clostridial
      vaccinations seems to be too long for adequate protection.

PMID- 9027546
TI  - Evaluation of corn and sorghum distillers byproducts.
AB  - Two trials were conducted to determine the feeding value of sorghum distillers
      byproducts. Trial 1, a finishing trial, used 160 yearling steers (327 kg).
      Treatments consisted of dry-rolled corn (DRC) control, sorghum wet distillers
      grains (SWDG), sorghum wet distillers grains plus solubles (SWDGS), and sorghum
      dried distillers grain plus solubles (SDDGS). Distillers byproducts were fed at
      40% of the diet DM. Cattle fed diets containing SWDG, SWDGS, or DRC were similar
      in efficiency of gain (P > .10); cattle fed SDDGS were less efficient (P < .10)
      than all other treatments. Sorghum wet distillers grains, SWDGS, and SDDGS
      contained 96, 102, and 80% relative NEg of corn, respectively. In Trial 2, 16
      crossbred lambs (55 kg) were used to determine the digestibility of sorghum and
      corn distillers byproducts. Byproducts were fed at 80% of the diet DM and
      treatments consisted of corn wet distillers grains (CWDG), corn dried distillers
      grains plus solubles (CDDGS), SWDG, and SDDGS. Neutral detergent fiber
      digestibility was not different among treatments (P > .10). Corn wet distillers
      grains were higher in true nitrogen (P < .001), apparent nitrogen (P < .01), and
      organic matter digestibility (P < .05) than SWDG. Wet distillers byproducts were
      higher (P < .01) in apparent organic matter and nitrogen digestibility than dried
      distillers byproducts. Digestibility of distillers byproducts and subsequent
      energy values are influenced by type of grain used in the fermentation process
      and drying of the finished byproduct.

PMID- 9027547
TI  - Evaluation of wet distillers composite for finishing ruminants.
AB  - Two trials evaluated the effect of a composite of feed ingredients formulated to
      be similar in nutrient composition to wet distillers byproducts on finishing
      performance of sheep and cattle. Trial 1 used 60 crossbred lambs (31 kg) assigned
      to one of four treatments: dry-rolled corn (DRC) control, dried distillers grains
      plus solubles, wet corn gluten feed (WCGF), and wet distillers grains composite
      (COMP1). The COMP1 consisted (DM basis) of 47.5 WCGF, 11.9% condensed distillers
      solubles, 30.5% corn gluten meal, 9.7% tallow, and .4% dicalcium phosphate and
      was fed at 40% of the diet DM. Lambs fed the COMP1 diet were 27% more efficient
      (P < .10) than lambs fed WCGF and 12% more efficient (P > .10) than lambs fed
      DRC. In Trial 2, 60 yearling crossbred steers (272 kg) were assigned to one of
      five treatments: DRC control, WCGF, wet distillers grains composite (COMP2),
      COMP2 minus tallow (-FAT), or COMP2 minus corn gluten meal (-CGM). the COMP2
      consisted (DM basis) of 65.7% WCGF, 26.3% corn gluten meal, and 8.0% tallow and
      was fed at 40% of the diet DM. Steers fed COMP2 were more efficient (P < .10)
      than steers fed DRC or WCGF, and the steers fed -FAT and -CGM were intermediate
      to these three dietary treatments. A composite diet of WCGF, condensed distillers
      solubles, corn gluten meal, and tallow, formulated to be similar in nutrient
      composition to wet distillers byproducts, may improve feed efficiency compared
      with WCGF or DRC.

PMID- 9027548
TI  - Genetic relationships among production traits and rebreeding performance.
AB  - We studied effects of selection for increased daily gain, reduced backfat,
      increased number of piglets born alive, and increased 21-d litter weight on
      interval from weaning to farrowing (IWF) of two commercial populations of
      purebred Large White (LW) and Landrace (LR) lines with each represented in two
      farms. The analysis took into account that normal and prolonged intervals could
      be distinguished. Distributions of IWF were described by a mixture of a normal
      and an exponential distribution. Observed intervals were transformed to the
      probability of being a prolonged interval, using the mixed density function.
      Incidence of normal intervals was less in LR than in LW sows and was least in
      first-litter sows. Heritability estimates of IWF ranged from zero to .24 across
      parities and farms. Genetic trend within breed and farm was different from zero
      (P < .05) for each trait under selection, except backfat on Farm 2. Genetic
      correlations between the traits under selection and IWF were inconsistent across
      farms. Differences in estimated breeding value for the traits under selection
      between sows with a normal and a prolonged interval were significant only on Farm
      1 in the Large White breed, when only observed intervals were analyzed. Including
      culled sows in the analysis as sows with a prolonged interval yielded consistent
      differences for average daily gain and backfat, such that genetic selection for
      improved production would increase the liability for a prolonged interval.
      Culling sows for delayed estrus apparently overcame this problem on Farm 2 but
      not on Farm 1, on which a trend of increasing incidence of prolonged intervals
      was observed.

PMID- 9027549
TI  - Influence of partitioning data by sex on genetic variance and covariance
      components for weaning weight in beef cattle.
AB  - Heterogeneity of (co)variance components (VC) by sex is currently accounted for
      in national genetic evaluations for Simmental cattle. Parameters used in the
      national evaluation program are estimated from data split into male, female, and
      steer populations. Analyzing only male data does not account for selection of
      females, and vice versa. To determine the impact of selection, a Monte Carlo
      simulation was used, and estimates of VC for weaning weight were obtained when
      data were partitioned by sex. Weaning weight data were simulated using
      homogeneous VC for males and females for random and selected populations.
      Restricted maximum likelihood estimates were obtained for direct and maternal
      genetic and permanent and temporary environmental variances and genetic
      covariance between direct and maternal effects by analyzing complete or split
      data. Estimates differed (P < .01) from input values in data from selected
      populations split by sex, yielding a spurious heterogeneity of VC for sex. The
      heterogeneity was reduced in models using genetic groups but not completely
      removed. Splitting data by sex also influenced VC estimates in data simulated
      with heterogeneous VC for males and females.

PMID- 9027550
TI  - Relationship between sire x year interactions and direct-maternal genetic
      correlation for weaning weight of Simmental cattle.
AB  - The interrelation of sire x year interactions (SY) and direct-maternal genetic
      correlation (rdm) for weaning weight was examined for bias in estimating rdm.
      Weaning weight records were simulated using models containing SY (D1), rdm (D2),
      or both (D3). When D1 data were analyzed ignoring SY, a nonzero rdm was observed,
      and direct and maternal genetic variance estimates were inflated. Analysis of D2
      data ignoring rdm did not reveal a spurious SY, and direct and maternal genetic
      variance estimates were deflated. On application to weaning weights of Simmental
      cattle, the model ignoring SY resulted in a direct-maternal genetic correlation
      estimate of -.29. The model using both SY and rdm fit the data better (P < .01).
      The SY variance represented only 3% of phenotypic variance but explained 62% of
      the covariance between direct and maternal genetic effects estimated ignoring SY.
      However, a negative estimate of the genetic correlation (-.14) was still
      obtained.

PMID- 9027551
TI  - Genetic analysis of discrete reproductive traits in sheep using linear and
      nonlinear models: I. Estimation of genetic parameters.
AB  - Repeated records on fertility, litter size, and ovulation rate of Rambouillet
      ewes and on fertility and litter size of Finnsheep ewes were used to estimate
      heritabilities and repeatabilities with linear and nonlinear sire and animal
      models. Linear sire (LSM) and animal models were used with all traits. Nonlinear
      models were the threshold, Poisson, and negative binomial. Threshold sire (TSM)
      and animal models were used with all traits. Litter size and ovulation rate were
      analyzed also with Poisson sire and animal models and with negative binomial sire
      and animal models. Variance components for linear models were estimated using
      REML; in the threshold, Poisson, and negative binomial, they were estimated using
      approximate marginal maximum likelihood. Poisson and negative binomial analyses
      yielded results difficult to interpret due to problems in variance component
      estimation. Animal models resulted in slightly greater estimates of heritability
      for fertility than did sire models, but ovulation rate heritability estimates
      from sire models were much greater than estimates form animal models. Differences
      between sire and animal models for heritability estimates for litter size were
      not consistent. Threshold models resulted in higher heritability estimates for
      all traits in both breeds and with both sire and animal models. In general,
      repeatabilities were consistent across models. For example, LSM (TSM)
      repeatabilities were .10 (.14) for fertility, .20 (.25) for litter size, and .25
      (.29) for ovulation rate in the Rambouillet, and .17 (.17) for fertility and .11
      (.13 for litter size in the Finnsheep.

PMID- 9027552
TI  - Genetic analysis of discrete reproductive traits in sheep using linear and
      nonlinear models: II. Goodness of fit and predictive ability.
AB  - The performance of linear and nonlinear sire and animal models in the analyses of
      reproductive traits (fertility, litter size, and ovulation rate) in two sheep
      populations (Rambouillet and Finnsheep) was compared in terms of goodness of fit
      and predictive ability. Linear sire (LSM) and animal (LAM) models were used with
      all traits. Nonlinear models were the threshold, Poisson, and negative binomial.
      Threshold sire (TSM) and animal (TAM) models were also used with all traits.
      Litter size and ovulation rate were analyzed also with Poisson and negative
      binomial sire (PSM and NBSM, respectively) and animal (PAM and NBAM,
      respectively) models. Variance components were those reported in the companion
      article. For PAM a new set of variance components derived from estimates found
      with the linear animal model also was used (PAM-L). Mean squares error (MSE) and
      correlations between fitted and observed values were used to assess goodness of
      fit. Predictive ability was assessed by partitioning the data sets for the
      different traits into two subsets with the restriction that all levels of fixed
      effects were represented in each subset. Parameters from one subset were employed
      to predict observations in the other, and then MSE and correlations between
      observed and predicted values were used as criteria for model comparison. Within
      estimation procedure, breed, and trait, goodness of fit of sire and animal models
      was similar. Linear and threshold models resulted in similar fit, and both
      outperformed Poisson and negative binomial models. In terms of predictive
      ability, linear and threshold models performed only slightly better than Poisson
      and negative binomial models. Goodness of fit and predictive ability generally
      were better when models included permanent environmental effects.

PMID- 9027553
TI  - Changes in proportions of empty body depots and constituents for nine breeds of
      cattle under various feed availabilities.
AB  - Mature cows (146) representing Angus, Braunvieh, Charolais, Gelbvieh, Hereford,
      Limousin, Pinzgauer, Red Poll, and Simmental breeds were slaughtered to
      contribute to the investigation of the effect of various feed availabilities on
      body composition. Weights recorded when cows were placed on feed were used to set
      daily diets at four rates of intake within each breed (55, 76, 96, and 111 g
      DM/[kg wt.75.d]). Cows remained on their assigned daily feed allotment throughout
      the study (3 to 5 yr). On the day of slaughter, shrunk live weights were
      recorded. Chemical determinations of protein (nitrogen x 6.25), ether extractable
      lipid, ash of dry matter, and moisture for hide and offal were obtained for all
      cows. Chemical determinations of these same constituents were obtained for the
      carcass soft tissue of 98 cows. Relationships among estimator traits carcass ash,
      warm carcass weight, resistive impedance, and carcass water from the 97 carcasses
      were used to predict the carcass constituents for the remaining 49 cows. Within
      breed, relationships between proportions of fat and empty body (sum of fat, ash,
      water, and protein from the three body pools of hide, offal, and carcass) were
      used to estimate empty body weight at 251 g fat/kg (standard reference body
      weight) for each of the nine breeds. Proportions of offal, carcass, hide,
      chemical constituents, and selected abdominal and thoracic organs relative to
      empty body weight from cows that attained weight stasis were regressed on one
      minus the ratio of individual actual empty body weight to breed standard
      reference weight. Among mature cows attaining weight stasis at various feeding
      rates, the proportion of offal remained constant, proportions of fat in carcass,
      hide, and offal increased with increasing feed level, and proportions of water
      and protein decreased. Significant variation (P < .01) attributable to breed in
      proportions of carcass, offal, hide, chemical constituents of the hide and offal,
      water, and protein of the carcass and selected organs was observed.

PMID- 9027554
TI  - Insulin and hydrocortisone, but not triiodothyronine, are required for the
      differentiation of pig preadipocytes in primary culture.
AB  - The objective of this study was to establish optimal conditions for the primary
      culture of pig preadipocytes. We cultured pig preadipocytes for 10 d and studied
      the effects of insulin, hydrocortisone, and triiodothyronine (T3) added to serum
      free basal medium on differentiation and gene expression of lipoprotein lipase an
      early marker, and adipsin, a late marker of preadipocyte differentiation. Insulin
      alone and hydrocortisone alone stimulated a low level of cell differentiation, as
      indicated by an increase in glycerol-3-phosphate dehydrogenase activity. When
      added together, insulin and hydrocortisone had a synergistic effect on cell
      differentiation. When combined with insulin or hydrocortisone, T3 had no effect
      on cell differentiation, indicating that T3 is not required in porcine
      preadipocyte culture. Gene expression studies also showed that removal of insulin
      or hydrocortisone from complete serum-free medium reduced both early and late
      marker mRNA. As expected, removal of T3 had no effect on the gene expression of
      early and late marker mRNA. We conclude that insulin and hydrocortisone, but not
      T3, are required for the differentiation of pig preadipocytes in primary culture.

PMID- 9027555
TI  - Effect of retinoic acid on differentiation of cultured pig preadipocytes.
AB  - We studied the effect of retinoic acid on the differentiation of cultured porcine
      preadipocytes. Porcine preadipocytes were cultured in serum-free medium (DME/F12
      medium containing 100 nM insulin, 10 micrograms/mL transferrin, and 50 ng/mL
      hydrocortisone). Addition of increasing amounts of retinoic acid (1 nM to 20
      microM) to the medium reduced glycerol-3-phosphate dehydrogenase (GPDH) activity,
      a late marker of preadipocyte differentiation. At lower concentrations (0.1 to 10
      nM), retinoic acid had no effect on the GPDH activity. Addition of retinoic acid
      (10 microM) for 24 h during the early stage of development (d 1) greatly
      inhibited the GPDH activity. After the cells were differentiated, however,
      retinoic acid no longer had any effect. Therefore, retinoic acid was most
      effective in undifferentiated cells. Following a 24-h exposure of porcine
      preadipocytes to retinoic acid at d 1, Northern blot analysis showed that there
      was a decrease in lipoprotein lipase and adipsin mRNA levels. The results suggest
      that retinoic acid is a potent inhibitor of porcine preadipocyte differentiation
      in primary culture.

PMID- 9027556
TI  - The effect of electrical stimulation on the water-holding, capacity and protein
      denaturation of two bovine muscles.
AB  - The effect of low-voltage electrical stimulation on the water-holding capacity
      and protein denaturation of bovine longissimus thoracis and semimembranosus was
      studied in eight electrically stimulated (85 V, 14 Hz, 15 s; immediately after
      slaughter) and eight nonstimulated Friesian Holstein bull carcasses. At 24 h
      postmortem longissimus thoracis and semimembranosus were sampled for drip loss,
      thaw loss, filter paper wetness, myofibrillar water-holding capacity, protein
      content of drip, protein solubility, myofibrillar ATPase-activities, and bound
      phosphorylase. Electrical stimulation resulted in higher (P < .05) drip losses
      and filter paper wetness and lower (P < .05) myofibrillar water-holding capacity
      of semimembranous samples. The increased drip loss coincided with decreased (P <
      .05) sarcoplasmic protein solubility, decreased (P < .05) myofibrillar ATPase
      activity, and decreased (P < .05) protein concentration of drip. In the
      longissimus thoracis, electrical stimulation resulted in a lower (P < .05)
      myofibrillar water-holding capacity. However, this was not reflected in higher
      drip losses. In this muscle, only a decreased (P < .05) sarcoplasmic protein
      solubility and increased (P < .05) amount of bound phosphorylase was observed.
      The results indicated that the negative effect of electrical stimulation on drip
      loss is possibly the result of myosin denaturation, which is determined by
      postmortem pH and temperature fall and thus varies by muscle studied.
      Sarcoplasmic protein denaturation seemed not to be involved in determining water
      holding capacity.

PMID- 9027557
TI  - Phenotypic characterization of Rambouillet sheep expressing the callipyge gene:
      II. Carcass characteristics and retail yield.
AB  - Paternal half-sibling Rambouillet ram lambs (n = 18) representing two muscle
      phenotypes were slaughtered at 54.5 kg to evaluate carcass characteristics and
      composition. Lambs were produced from a sire that was heterozygous for the
      callipyge gene. Carcasses were broken into wholesale and retail cuts to evaluate
      percentage bone-in retail yield of carcasses at various fat trim levels and
      percentage of boneless retail cuts. Retail cuts were trimmed to .6 and then to 0
      cm fat trim and bones were removed to determine boneless, closely trimmed retail
      cut yield. Chemical composition was determined using proximate analysis. Lambs
      expressing the callipyge gene had higher dressing percentages (57.3 vs 53.9), leg
      (14.4 vs 11.0) and conformation (14.4 vs 11.0) scores, and larger longissimus
      muscle (LM) areas (17.6 cm2 vs 10.3 cm2). All other carcass measurements were
      similar between phenotypes except marbling score, which was higher (417.8 vs
      325.6) for controls. Lambs expressing the callipyge gene had a higher (40.2 vs
      32.9) percentage boneless retail yield than controls. Retail yield of the
      boneless shoulder did not differ between phenotypes (8.9 vs 8.0). All other
      percentages of boneless retail cuts were higher (P < .02) for lambs expressing
      the callipyge gene. Carcasses from lambs with the callipyge gene had higher
      protein (16.6 vs 15.2), moisture (63.6 vs 58.6) and ash (.85 vs 77) percentages
      and lower fat (18.9 vs 25.4) percentages than controls. These data suggest that
      ram lambs expressing the callipyge gene have an advantage in retail yield and
      carcass conformation when compared to normal-muscled half-siblings.

PMID- 9027558
TI  - Phenotypic characterization of rambouillet sheep expression the callipyge gene:
      III. Muscle weights and muscle weight distribution.
AB  - Paternal half-sibling Rambouillet ram lambs (n = 18) representing two muscle
      phenotypes were slaughtered at 54.5 kg to evaluate the effect of the callipyge
      gene on muscle mass. Lambs were produced from a sire that was heterozygous for
      the callipyge gene. Nineteen muscles were dissected from the right side of each
      carcass to evaluate muscle weights relative to carcass weight. Excised muscle
      mass as significantly higher (42%) for lambs exhibiting a callipyge muscle
      phenotype than for half-siblings. In the pelvic limb, all excised muscles except
      the peronius tertius were larger in lambs expressing the callipyge gene (P <
      .001). In the torso, the longissimus (P < .001), psoas major (P < .001), and
      psoas minor (P < .01) were larger in lambs with the callipyge phenotype. In the
      thoracic limb, the biceps brachii (P < .001) triceps brachii (P < .002), and
      extensor carpi radialis (P < .01) were larger in lambs with the callipyge
      phenotype. Total pelvic limb (P < .001) torso (P < .001), and thoracic muscle
      weights were higher (P < .01) in lambs with the callipyge phenotype. Callipyge
      lambs had a higher (P < .01) percentage of excised muscle weight in the pelvic
      limb and torso and a lower (P < .01) percentage in the thoracic limb when
      compared to controls. These data indicate that the magnitude of expression of the
      callipyge gene is dependent upon the location of the muscle on the body and that
      the increased muscle mass was concentrated in the leg and loin.

PMID- 9027559
TI  - The use of urea dilution for estimation of carcass composition of Holstein steers
      at 3, 6, 9, and 12 months of age.
AB  - Every 3 mo for a 2-yr period, two weaned Holstein steer calves (94.5 kg) were
      randomly assigned to each of four slaughter age groups (3, 6, 9, and 12 mo). Urea
      dilution was performed before slaughter, and urea space (US) was calculated as
      total volume and as a percentage of body weight (BW) and empty body weight (EBW).
      The relationships between US (kg, % EBW and % BW), BW, and EBW and carcass soft
      tissue composition (protein, fat, moisture, and ash) were studied. One- and two
      pool models were fitted using the urea dilution data and the coefficients of
      those equations (zero time, A + B), and the intercepts of compartments A and B
      were used to estimate body volume. Body weight and EBW effectively predicted the
      amount of water, fat, and protein in the carcass soft tissue. Equations expressed
      in kilograms were more accurate than those expressed as percentages. Urea space
      overestimated body water, probably because of the fast rate of urea disappearance
      in plasma. Correlation coefficients between US and carcass soft tissue water (kg)
      based on the pooled data ranged from .74 at 6 min to .48 at 42 min after
      infusion. The biexponential models coefficients explained more of the variation
      of carcass soft tissue composition than US; correlation coefficients using volume
      B and the soft tissue composition (in kg) with pooled data were .78 (water), .68
      (fat), .69 (ash), and .76 (protein). The relationships between A and soft tissue
      composition were weaker (water .59, fat .51, ash .58 and protein .59). The
      highest correlation coefficients were obtained when A + B was used for water,
      fat, ash, and protein (.83, .70, .74 and .81, respectively). Equations combining
      BW, EBW, and two-model coefficients (A, B, A + B) explained much of the variation
      of soft tissue composition. No significant benefit was found in using the urea
      space at various times after infusion over BW or EBW alone to estimate carcass
      soft tissue composition in Holstein steers.

PMID- 9027560
TI  - Evaluation of the 15N-isotope dilution technique for determining the recovery of
      endogenous protein in ileal digestion of pigs: effect of dilution in the
      precursor pool for endogenous nitrogen secretion.
AB  - Three barrows, average initial BW of 35 kg, were fitted with a re-entrant cannula
      at the distal ileum and catheters in each of the external jugular veins. The
      barrows were fed twice daily a diet containing barley as the sole source of
      protein. A 1-d intravenous infusion of saline was followed by an 8-d continuous
      infusion of [15N]leucine at a rate of 30 mg/(kg BW x d). Blood samples, taken
      hourly for 9 d, were pooled over the 12-h period between feeding. Ileal digesta
      were collected hourly on d 3 and 8 of the [15N]leucine infusion and pooled over
      12 and 24 h. Enrichments (atom percentage excess 15N) in nitrogen (N), leucine,
      isoleucine, valine and alanine were measured in the trichloroacetic acid (TCA)
      soluble and -insoluble fractions of plasma and in ileal digesta. Although the
      enrichments in N were similar in all pools, enrichments in amino acids in the TCA
      soluble fraction of plasma were at least twice that in the TCA-insoluble fraction
      and in ileal digesta. The estimated contributions of endogenous N and amino acids
      to total N and amino acids in ileal digesta were 82.3 +/- 9.38, 39.0 +/- 3.83,
      43.8 +/- 6.50, 51.9 +/- 3.24, and 51.9 +/- 9.80 for N, leucine, isoleucine,
      valine and alanine, respectively. The results from this study indicate that
      enrichments in total N in the TCA-soluble fraction of plasma may not accurately
      reflect enrichments in endogenous N secreted into the intestinal lumen. This
      factor should be considered when using the 15N-isotope dilution technique to
      estimate the recovery of endogenous protein in ileal digesta of pigs fed protein
      containing diets.

PMID- 9027562
TI  - Growth performance and intestinal microbial populations of growing pigs fed diets
      containing sucrose thermal oligosaccharide caramel.
AB  - Four experiments were conducted to determine growth performance and changes in
      intestinal microbial populations of growing pigs fed diets containing sucrose
      thermal oligosaccharide caramel (STOC). Ninety-six barrows and 96 gilts were
      group-fed experimental nursery diets for 32 d after weaning in both Exp. 1 and 2.
      For each experiment, pigs were divided into four groups of 48 pigs and were fed
      either control, antibiotic (Apramycin sulfate, 34 mg/kg), 1% STOC, or 2% STOC
      diets for 32 d after weaning. Each diet was replicated six times with eight pigs
      per replication. Pigs were either orally gavaged (Exp 1) with water of STOC (2 g
      per pig) or pigs were creep-fed (Exp 2) either a control diet or a 2% STOC diet
      for 5 d before weaning (33 d). At the end of Exp 1 and 2, cecal material was
      collected for enumeration of total aerobes, total anaerobes, coliforms,
      lactobacilli, and bifidobacteria. Gilts (96 per experiment) used in Exp. 3 and 4
      were weaned at 26 d and fed experimental nursery diets for 32 d. They were fed
      either a control or 1% STOC diet and were otherwise treated as previously
      described. There were no significant effects of STOC or antibiotic on ADG, ADFI,
      feed efficiency, or cecal microbial populations in pigs in this study. Feeding
      diets containing either antibiotic of STOC did not improve animal performance or
      change intestinal bacterial populations in the present study.

PMID- 9027561
TI  - Evaluation of the 15N-isotope dilution technique for determining the recovery of
      endogenous protein in ileal digesta of pigs: effect of the pattern of blood
      sampling, precursor pools, and isotope dilution technique.
AB  - The 15N-enrichments (atom percentage excess) were determined in the plasma free
      amino acids of blood samples taken at the time of feeding and in samples taken
      hourly and pooled over 12 h, as well as in ileal digesta, crude mucin, and
      bacteria collected at the distal ileum of pigs fed barley while continuously
      administered [15N]leucine intravenously. The branched-chain amino acids were the
      only indispensable amino acids to exhibit incorporation of 15N (P < .05). All
      dispensable amino acids exhibited some incorporation. Enrichments in free leucine
      and alanine were higher (P < .02) in blood samples taken at the time of feeding,
      compared to those in pooled blood samples, resulting in an underestimation of the
      endogenous ileal recoveries of these amino acids. Enrichments in amino acids in
      crude mucin were usually similar to those in pooled plasma samples, providing
      some support for the use of plasma free amino acids to estimate enrichments in
      endogenous amino acids in ileal digesta. Enrichments in bacteria were not
      different (P > .05) from those in ileal digesta. The recoveries of endogenous
      amino acids in ileal digesta determined with the [15N]leucine and 15N-amino acid
      dilution techniques demonstrate the overestimation of these criteria with the 15N
      isotope dilution technique, applied in its current form, and suggest that
      modifications in the composition of endogenous protein can occur when pigs are
      fed protein-containing diets. These study supports the use of 15N-isotope
      dilution techniques, with modifications, for determining the recovery of
      endogenous protein in ileal digesta of pigs fed protein-containing diets.

PMID- 9027563
TI  - Effect of ergotamine and ergonovine on thermal regulation and cardiovascular
      function in cattle.
AB  - Research was conducted to determine whether individual ergot alkaloids could
      induce signs of fescue toxicosis. Nine Angus heifers received single i.v.
      injections of ergotamine tartrate, ergonovine maleate, and saline vehicle in a
      simple cross-over design. Each heifer received a different compound each week and
      all treatments during the study. Physiological traits measured 15 min before and
      30, 60, and 90 min after treatment were respiration rate, rectal and skin
      temperatures, systolic and diastolic pressures, and heart rate. Blood samples
      were collected 5 min before and 105 min after treatments to assess plasma
      prolactin concentrations. Heifers were on a fescue-free diet in drylot. Ambient
      temperature averaged 35 degrees C during data collection. A treatment x time
      interaction existed (P < .05) for respiration rate and prolactin concentrations.
      Ergot alkaloids altered (P < .05) all traits across time, except rectal
      temperature. Heifers under the influence of ergot alkaloids exhibited
      significantly lower skin temperature, heart rate, and prolactin and had higher
      respiration rate and blood pressure. Results indicated that individual ergot
      alkaloids administered i.v. induced signs of fescue toxicosis in cattle.

PMID- 9027564
TI  - Molecular cloning and mRNA expression of the bovine insulin-responsive glucose
      transporter (GLUT4).
AB  - Insulin-response glucose transporter GLUT4 is a member of the glucose transporter
      family (GLUT) and is present exclusively in muscle and adipose tissue. It is a
      target of insulin action in humans and rodents. To clarify the molecular
      structure of bovine GLUT4, its GLUT4 cDNA was cloned by the RT-PCR method.
      Several cDNA clones corresponding to the different regions of GLUT4 were obtained
      by amplifying reverse-transcriptase products of RNA extracted from Holstein
      cattle skeletal muscle. Nucleotide sequence analysis of the cDNA clones revealed
      that bovine GLUT4 cDNA was composed of 2,656 base pairs with a coding region for
      a 509 amino acid protein. The deduced amino acid sequence was 64% and 92%
      identical with bovine GLUT1 (GLUT ubiquitously expressed in all tissues) and rat
      GLUT4, respectively. Although the amino acid sequence of the GLUT4 COOH-terminal
      region is highly conserved among the species so far reported, one amino acid
      (Asp) of the region was replaced by His in bovine GLUT4. The tissue distribution
      of GLUT4 was also examined by Northern blot analysis using a probe prepared from
      the bovine cDNA. GLUT4 mRNA was detected in skeletal muscle, heart, and adipose
      tissue, but not in liver, kidney, lung, brain, or spleen. Such a distribution is
      essentially the same as in humans and rodents, suggesting that GLUT4 is an
      insulin-responsive glucose transporter in cattle.

PMID- 9027565
TI  - Concentration of gonadotropin-releasing hormone receptor messenger ribonucleic
      acid in pituitary tissue of orchidectomized sheep: effect of passive immunization
      against gonadotropin-releasing hormone.
AB  - The effect of immunoneutralization of gonadotropin-releasing hormone (GnRH) on LH
      secretion and concentrations of GnRH receptor, GnRH receptor mRNA, and
      gonadotropin subunit mRNA in pituitary tissue of orchidectomized sheep (wethers)
      was assessed. Thirty-six wethers were assigned at random to one of six treatment
      groups (six wethers per group). Thirty wethers (groups 2 to 6) received 200 ml,
      (i.v.) of anti-GnRH antisera at passive immunization (PI). Anterior pituitary
      tissue was collected .5, 1, 2, 4, or 8 d after PI from wethers in groups 2 to 6,
      respectively. Pituitary tissue was also collected from unimmunized wethers (Group
      1). Intravenous administration of anti-GnRH sera increased anti-GnRH activity to
      69.1 +/- 7% (percentage of total 125I-labeled GnRH bound by a 1:1,000 serum:GEL
      PBS dilution) within 1 h of PI. Anti-GnRH activity declined gradually during the
      period after PI, and 8 d after PI anti-GnRH activity was 57.2 +/- 1.7%. Serum
      concentration of LH was significantly reduced, relative to the pretreatment (16.1
      +/- 1.8 ng/mL) level, within 4 h (7.6 +/- 1.5 ng/mL) of PI, and the LH level was
      10% of the pretreatment concentration 8 d after PI (1.6 +/- 0.2 ng/mL). Steady
      state concentration of GnRH receptor mRNA decreased progressively during the
      period after PI and was significantly reduced, relative to the level in
      unimmunized control wethers (.44 +/- .03 pg/micron total RNA) d after PI. Tissue
      concentrations of GnRH receptor and mRNA for the alpha, LH alpha, and FISH beta
      subunits were also reduced (P < .05) by PI. These data indicate that maintenance
      of steady-state concentrations of GnRH receptor and GnRH receptor mRNA requires
      continued GnRH stimulation.

PMID- 9027566
TI  - Expression of stress proteins in porcine tissues: developmental changes and
      effect of immunological challenge.
AB  - Immunoblot procedures were used to evaluate stress protein (SP) expression in
      developing and suckling piglet and in growing pigs challenged immunologically
      with bacterial lipopolysaccharide (LPS). The constitutively expressed 70-kDa SP
      (HSC70) and HSP60 were detected in the whole fetus at 30 d of development and in
      cardiac and skeletal muscle, liver, and lung at 50, 80, and 109 d. Expression of
      HSP60 was higher (P < or = .03) postnatally in cardiac and skeletal muscle and in
      lung, whereas HSC70 expression increased (P < or = .01) only in skeletal muscle.
      The stress-inducible 70-kDa SP (HSP70) was detected in skeletal muscle samples
      collected 4 d postnatally in two of the four piglets sampled. However, this SP
      was not detected in samples collected 18 d postnatally. In the LPS challenge
      study, HSP70 was detected only in liver and intestinal mucosa, and an
      unidentified protein of approximately 130 kDa was evident in liver and tissue.
      Expression of HSP70 in liver was not affected by LPS but doubled (P < or = .01)
      in the jejunal mucosa. Furthermore, although faintly evident in the mucosa of
      spiral colon of control pigs, HSP70 was clearly increased (P < = .01) in that of
      challenged pigs. Liver concentrations of the immunoreactive 130-kda protein were
      not influenced by LPS. The data presented herein indicate that tissue
      concentration of specific SP change in vivo with development age and that an
      immunological challenge increases the concentration of specific SP in some
      tissues.

PMID- 9027567
TI  - Administration of testosterone from day 13 of the estrous cycle to estrus
      increased the number of corpora lutea and conceptus survival in gilts.
AB  - The effects of exogenous androgens on the number of corporea lutea (CL) and
      conceptus survival were examined in crossbred gilts. In Exp. 1, gilts received 1
      mg of testosterone per day from d 13 (d = 0 first day of estrus, n = 21) or d 16
      until estrus (n = 23). Gilts in the vehicle group received corn oil (n = 20).
      Gilts were mated and on d 11.5 their concepti and CL were evaluated. In Exp. 2,
      conceptus survival was examined at the 4- to 8-cell, early blastocyst or hatching
      blastocyst stages for gilts given vehicle or 1 mg testosterone from d 13 (24
      gilts per group). In Exp. 3, gilts received 1 mg of androstenedione (n = 20) or
      vehicle (n = 18) per day from 13 d to estrus and then were mated and evaluated on
      d 11.5. Results from Exp. 1 indicated that the number of CL was greater (P < .04)
      in gilts treated with testosterone from d 13 to estrus than in gilts receiving
      vehicle (16.4 vs 14.8, respectively). Similarly, the number (P < .01) and
      recovery rate (P < .04) of blastocysts were greater in gilts treated with
      testosterone from d 13 to estrus than in gilts treated with testosterone from d
      16 to estrus in gilts receiving vehicle (number, 15.3 vs 12.8 or 12.8; recovery
      rate, 95 vs 87 or 86%, respectively). Gilts treated testosterone or vehicle did
      not exhibit differences (P > .05) in number of normal concepti at the 4- to 8
      cell and hatching stages. However, prior treatment with testosterone delayed
      conceptus death; gilts treated with testosterone had more (P < .01) normal
      concepti at the intermediate stage (early blastocyst) than those treated with
      vehicle (treatment x embryo stage interaction, P < .05). In Exp. 3,
      androstenedione treatment did not influence (P > .10) the number of CL or the
      number and recovery rates of d-11.5 blastocysts. Treating gilts with testosterone
      from d 13 of the estrous cycle to the following estrus increased the number of CL
      and blastocyst survival, perhaps by improving some, as yet unknown, aspect(s) of
      oocyte quality.

PMID- 9027568
TI  - Pattern of feed intake and associated metabolic and endocrine changes
      differentially affect postweaning fertility in primiparous lactating sows.
AB  - Effects of differential patterns of feed intake during lactation, associated
      metabolic and endocrine changes, and reproductive status after weaning were
      investigated in 26 primiparous sows suckled by six piglets. Sows were fed to
      appetite (Group AA; n = 9) from d 1 to 28 of lactation or restricted to 50% from
      d 22 to 28 (Group AR; n = 9) or from d 1 to 21 (Group RA; n = 8). Sow weight,
      backfat, and litter weights were recorded weekly. After weaning sows were tested
      twice daily for onset of estrus and inseminated twice using pooled semen. At d 28
      of gestation sows were slaughtered and reproductive tracts were recovered to
      determine ovulation rate and embryo number. Intensive blood sampling was carried
      out for 12-h periods on d 21 and before and after weaning on d 28 to characterize
      changes in plasma, LH, FSH, insulin, and IGF-I by RIA. Litter growth rates did
      not differ among groups. Feed-restricted sows lost more (P < .01) body weight and
      backfat than those fed to appetite. During periods of feed restriction in AR and
      RA sows, postprandial insulin, mean IGF-I, and LH pulse frequency were less than
      in AA sows fed to appetite. All sows exhibited an increase (P < .001) in LH
      pulsatility in response to weaning. After weaning, no differences were observed
      in insulin, LH, or FSH, although IGF-I was still lower (P <.05) in AR sows. These
      results demonstrate that the pattern of metabolic change in the primiparous
      lactating sows exerts differential effects on fertility after weaning.

PMID- 9027569
TI  - Supplemental dietary chromium does not influence ACTH, cortisol, or immune
      responses in young calves inoculated with bovine herpesvirus-1.
AB  - Twelve Holstein bull calves (6 to 8 wk of age) were used to determine the
      influence of supplemental dietary Cr on ACTH, cortisol, and immune responses of
      calves experimentally inoculated with bovine herpesvirus-1 (BHV-1). Calves
      supplemented with Cr received 3 mg Cr/d (Chromium, n = 6) of a high-Cr-yeast
      product. Following 53 d of treatment, all calves were fitted with jugular
      catheters, and blood samples were collected every 4 h into tubes containing ETDA.
      Twenty-four hours later, all calves were inoculated intranasally with BHV-1 (1 x
      10(7) plaque-forming units in each naris). Serial blood collection continued at 4
      h intervals for 6 d. Plasma was harvested, immediately frozen in liquid nitrogen,
      and stored at -20 degrees C. Individual rectal temperatures and urine samples
      were collected at the same time each day. Rectal temperatures were elevated (P <
      .05) on d 2, 3, 4, and 5 but were not affected by Cr treatment. Treatment with Cr
      did not affect secretion of ACTH, cortisol, or plasma tumor necrosis factor
      alpha, although clear circadian variation in ACTH and cortisol occurred. No
      differences were detected in the concentrations of trace minerals excreted daily
      in the urine, lymphocyte proliferative response to mitogen stimulation, and
      neutrophil bactericidal function. The acute phase proteins, ceruloplasmin and
      fibrinogen, also were not affected by treatment or viral challenge. These data
      suggest the Cr supplementation using high-Cr yeast (3 mg/d) did not alter stress
      responses of calves experimentally inoculated with BHV-1.

PMID- 9027570
TI  - Effect of forage quality and monensin on the ruminal fermentation of fistulated
      cows fed continuously at a constant intake.
AB  - A ruminal fermentation study was used to investigate the relationship between
      forage quality and monensin-dependent amino acid-sparing. Two fistulated cows
      were fed three concentrations of chopped (2.5 to 5.0 cm in length) timothy and
      alfalfa hays (100:0, 50:50 and 0:100) and two levels of monensin (0 and 350
      mg.cow-1.d-1). The diets were offered 12 times per day (9 kg of DM/d), and the
      rumen reached a steady-state, reducing animal and day variation. Alfalfa hay had
      1.4 times more CP and 1.4 times less NDF than timothy hay, and the substitution
      of timothy with alfalfa increased (P < .05) ruminal ammonia. Monensin had no
      effect on total ruminal ammonia when timothy hay was present in the diet, and it
      increased total ruminal ammonia with the 100% alfalfa diet. Effects on ruminal
      ammonia were, however, confounded by monensin-dependent decreases in ruminal pH
      (P < .05). Dissociated ammonia, the species most likely to be adsorbed from the
      rumen, declined when monensin was added to the 100% timothy diet (P < .05).
      Monensin had no effect on dissociated ammonia if alfalfa was 50% or 100% of the
      forage, but it counteracted alfalfa-dependent decreases in bacterial protein (P <
      .05). The idea that monensin could spare amino acids was supported by the
      observation that monensin decreased (P < .001) the specific activity of
      deanimation and increased bacterial protein at all combinations of alfalfa and
      timothy. Increases in bacterial protein could be explained by monensin-dependent
      increases in total VFA.

PMID- 9027571
TI  - Sulfur amino acid utilization by growing steers.
AB  - Studies were conducted to quantify sulfur amino acid requirements of growing
      steers. In Exp. 1, six steers (160 kg) were used to determine the methionine
      requirement in the presence of excess L-Cys. Treatments were abomasal infusion of
      water only or water plus 2, 4, 6, 8, or 10g/d of L-Met. Steers were fed 2.4 kg/d
      DM of a diet designed to minimize basal Met supply to the small intestine.
      Continuous ruminal infusions of VFA (506 g/d) and abomasal infusions of dextrose
      (150 g/d) increased energy supply to the abomasum. Break-point analysis estimated
      maximal N retention at 5.8 g/d supplemental L-Met. The basal absorbable Met
      supply was 2.1 g/d; therefore, the total Met requirement was 7.9 g/d when excess
      Cys was available. In Exp. 2, five steers (195 kg) were used to determine the
      efficiency of transsulfuration. Treatments were abomasal infusion of water only
      or water plus 1.62 or 3.25 g/d L-Cys or 2 o4 g/d L-Met. Diet and infusions were
      similar to those on Exp. 1, except the amino acid mixture was devoid of Cys and
      all steers received 4 g/d L-Met to make total sulfur amino acids, but not
      necessarily Met, limiting. Nitrogen retention increased in response to Met but
      not Cys infusion and was maximized at 2 g/d supplemental L-Met; thus, the total
      Met requirement was near 8.4 g/d when the Cys supply was 2.1 g/d. Supplemental
      Cys did not spare Met, suggesting that nonprotein functions of Met may be
      quantitatively important.

PMID- 9027573
TI  - Assessment of stress during handling and transport.
AB  - Fear is a very strong stressor, and the highly variable results of handling and
      transportation studies are likely to be due to different levels of psychological
      stress. Psychological stress is fear stress. Some examples are restraint, contact
      with people, or exposure to novelty. In many different animals, stimulation of
      the amygdala with an implanted electrode triggers a complex pattern of behavior
      and autonomic responses that resemble fear in humans. Both previous experience
      and genetic factors affecting temperament will interact in complex ways to
      determine how fearful an animal may become when it is handled or transported.
      Cattle trained and habituated to a squeeze chute may have baseline cortisol
      levels and be behaviorally calm, whereas extensively reared animals may have
      elevated cortisol levels in the same squeeze chute. The squeeze chute is
      perceived as neutral and non-threatening to one animal; to another animal, the
      novelty of it may trigger intense fear. Novelty is a strong stressor when an
      animal is suddenly confronted with it. To accurately assess an animal's reaction,
      a combination of behavioral and physiological measurements will provide the best
      overall measurement of animal discomfort.

PMID- 9027572
TI  - Site and extent of mineral absorption in lactating cows fed whole-crop cereal
      grain silage of alfalfa silage.
AB  - The site of apparent absorption of Na, K, Ca, P, Mg, and S in lactating dairy
      cows fed whole-crop barley, oats, triticale, or alfalfa silages was studied.
      Eight ruminally and duodenally cannulated Holstein cows with ad libitum access to
      a total mixed diet were assigned to one of four treatments as a replicated 4 x 4
      Latin square design. All diets contained the same concentrate (50%, DM basis)
      plus one experimental silage. The concentrations of Na, K, Ca, P, Mg, and S in
      the concentrate were .84, .71, .85, .78, .27, and 38%, respectively. Dry matter
      intake was higher (P < .05) for cows fed alfalfa and barely silages than for cows
      fed oats and triticale silages (19.6, 18.6, 16.7, and 17.2 kg/d, respectively).
      Alfalfa silage contained a higher concentration of all minerals studied than the
      cereal silages, except Na. Sodium flow at the duodenum was substantially greater
      than dietary intake and apparent total tract digestibilities ranged between 74.5
      and 85.2%. Secretion of P in the forestomach ranged from 34 to 61 g/d and the
      major site of absorption was in the intestine. The correlation between P intake
      and fecal excretion of P was significant (P < .001, r/ = .39) and linear.
      Potassium absorption occurred before the duodenum and in the intestine. Apparent
      digestibilities of K were lower for cereal silages (range 74.0 to 82.9%) than for
      alfalfa silage (88,7%). Apparent total tract digestibilities of Ca (28 to 32%),
      P(27 to 34%), and MG (17 to 24%) were similar for all diets so that Ca, P, and Mg
      absorption (g/d) reflected dietary Ca, P, and Mg levels. Data indicate that
      forage source can influence the site and extent of absorption, fecal output, and
      apparent digestibilities of macrominerals.

PMID- 9027574
TI  - The use of electrolyte solutions for reducing transport stress.
AB  - The transport and handling procedures imposed on beef cattle during the normal
      course of marketing can be a significant stressor. Factors including time off
      feed, water deprivation, mixing and the resulting behavioral problems, transport
      movement, unfamiliar noise, inclement weather, and so forth are often present and
      collectively result in live weight and carcass losses as well as degraded meat
      quality. In addition, a growing public concern regarding animal welfare in such
      situations is evident. Understanding how cattle adapt to and are influenced by
      these factors is a necessary first step in being able to reduce these stresses
      and a major research effort globally has been directed toward this end. Studies
      at the Lacombe Research Center have focused on understanding the role of
      electrolytes in attenuating transport and handling stress. Apparent in this
      research has been the consistent observation that transport and handling reduce
      blood pH, glucose concentration, and interstitial water space (P < .05), and
      increases in serum chloride. hemoglobin, urine sodium, and urine osmolality (P <
      .05) are evident. These changes are also accompanied by significant increases in
      the neutrophile/lymphocyte ratio. The application of oral electrolyte therapy,
      especially if similar in constituents to interstitial fluid, seems to attenuate
      these physiological changes. Resulting improvements in both live and carcass
      weights (less shrink) of up to several percent in treated animals as well as a
      reduction in meat quality degradation (reduced dark cutting) is evident in such
      trials. These studies suggest that the use of electrolyte therapy may be an
      effective means of reducing stress in transported cattle.

PMID- 9027575
TI  - Assessment of acute pain in farm animals using behavioral and physiological
      measurements.
AB  - In this paper various aspects of animal pain and methods for its assessment are
      considered. The responses of lambs and calves to castration and of lambs to tail
      docking are used to illustrate quantitative approaches to the recognition and
      assessment of acute pain in farm animals. the validation of physiological and
      behavioral measurements for assessment of pain is examined by relating
      measurements made from young lambs, after a range of treatments, to an
      independent ranking of the order of severity of the treatments.

PMID- 9027576
TI  - Introducing undergraduate students to animal science: a discovery course for non
      majors.
AB  - A discovery course titled "Living with Animals and Biotechnology" was taught to
      first-year students enrolled in disciplines other than Animal Science during the
      fall semesters of 1994 and 1995 at the University of Illinois. The course
      provided freshman students with an overview of how animals and biotechnology
      interact with our global society. It focused on technological achievements
      involving animals and how they influence the development of agriculture,
      medicine, and industry in our world. The course was conducted in a discussion
      format and met once a week. Upon successful completion of the course, students
      received one credit towards graduation. A total of 17 and 19 students completed
      the course for the two semesters that the course was offered. Most of the
      students (86%) were majors in the College of Liberal Arts and Science. Students
      rated the course high (4.85 +/- .06 with 5 = exceptionally high) and found the
      course a valuable learning experience (4.57 +/- .11 with 5 = very valuable). When
      surveyed 93% of the students said the discovery course gave them a much better
      impression of the Department of Animal Sciences. Most of the students (86%) said
      they would consider taking another animal science course. Offering one credit
      animal science discussion courses by faculty with diverse expertise introduces
      students to animal science. It also may stimulate student curiosity and
      excitement about the field of animal science.

PMID- 9027577
TI  - Rapid communication: cloning of a pig full-length natural resistance associated
      macrophage protein (NRAMP1) cDNA.

PMID- 9027578
TI  - Alternative splicing and cycling kinetics of myosin change during hypertrophy of
      human smooth muscle cells.
AB  - We investigated in vivo expression of myosin heavy chain (MHC) isoforms, 17 kDa
      myosin light chain (MLC17), and phosphorylation of the 20 kDa MLC (MLC20) as well
      as mechanical performance of chemically skinned fibers of normal and
      hypertrophied smooth muscle (SM) of human myometrium. According to their
      immunological reactivity, we identified three MHC isoenzymes in the human
      myometrium: two SM-MHC (SM1 with 204 kDa and SM2 with 200 kDa), and one non
      muscle specific MHC (NM with 196 kDa). No cross-reactivity was detected with an
      antibody raised against a peptide corresponding to a seven amino acid insert at
      the 25K/50K junction of the myosin head (a-25K/50K) in both normal and
      hypertrophied myometrium. In contrast, SM-MHC of human myomatous tissue strongly
      reacted with a-25K/50K. Expression of SM1/SM2/NM (%) in normal myometrium was
      31.7/34.7/33.6 and 35.1/40.9/24 in hypertrophied myometrium. The increased SM2
      and decreased NM expression in the hypertrophied state was statistically
      significant (P < 0.05). MHC isoform distribution in myomatous tissue was similar
      to normal myometrium (36.3/35.3/29.4). In vivo expression of MLC17a increased
      from 25.5% in normal to 44.2% in hypertrophied (P < 0.001) myometrium.
      Phosphorylation levels of MLC20 upon maximal Ca(2+)-calmodulin activation of
      skinned myometrial fibers were the same in normal and hypertrophied myometrial
      fibers. Maximal force of isometric contraction of skinned fibers (pCa 4.5, slack
      length) was 2.85 mN/mm2 and 5.6 mN/mm2 in the normal and hypertrophied state,
      respectively (P < 0.001). Apparent maximal shortening velocity (Vmax(appt),
      extrapolated from the force-velocity relation) of myometrium rose from 0.13
      muscle length s-1 (ML/s) in normal to 0.24 ML/s in hypertrophied fibers (P <
      0.001).

PMID- 9027579
TI  - Inhibition of MG-63 cell proliferation and PDGF-stimulated cellular processes by
      inhibitors of phosphatidylinositol 3-kinase.
AB  - Studies on a platelet-derived growth factor (PDGF) responsive osteosarcoma cell
      line, MG-63, were initiated to determine the effects of phosphatidylinositol
      (Ptdlns) 3-kinase inhibitors on serum-stimulated cell proliferation and PDGF
      stimulated DNA replication, actin rearrangements, or Ptdlns 3-kinase activity. In
      a dose-dependent manner, the fungal metabolite wortmannin and a quercetin
      derivative, LY294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one),
      inhibited serum-stimulated MG-63 cell proliferation. The mitogenic effects of
      PDGF on MG-63 cells, as determined by incorporation of [3H]-thymidine, were also
      substantially inhibited in the presence of 0.10 microM wortmannin or 10 microM
      Ly294002. Furthermore, MG-63 cells stimulated by PDGF form distinct actin-rich,
      finger-like membrane projections which are completely inhibited by either 0.10
      microM wortmannin or 10 microM LY294002. At these same concentrations, wortmannin
      and LY294002 were also effective at reducing levels of phosphatidylinositol 3
      phosphate in PDGF-stimulated MG-63 cells. Treatment of these cells with
      increasing concentrations of wortmannin reduced the level of PDGF stimulated
      tyrosine phosphorylation of the PDGF receptor but did not significantly affect
      the amount of the Ptdlns 3-kinase regulatory subunit, p85, associated with the
      receptor. Additionally, pretreatment of cells with 0.250 microM wortmannin
      followed by stimulation with PDGF resulted in a slightly reduced level of
      receptor autokinase activity; however, similar treatment with 50 microM LY294002
      did not affect the level of autokinase activity. These results demonstrate the
      effects of two different Ptdlns 3-kinase inhibitors on serum- and PDGF-stimulated
      MG-63 cell proliferation and PDGF-stimulated morphological changes and suggest a
      greater role for Ptdlns 3-kinase in these processes.

PMID- 9027580
TI  - Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by
      choline-deficiency.
AB  - Choline-deficiency causes liver cells to die by apoptosis, and it has not been
      clear whether the effects of choline-deficiency are mediated by methyl-deficiency
      or by lack of choline moieties. SV40 immortalized CWSV-1 hepatocytes were
      cultivated in media that were choline-sufficient, choline-deficient, choline
      deficient with methyl-donors (betaine or methionine), or choline-deficient with
      extra folate/vitamin B12. Choline-deficient CWSV-1 hepatocytes were not methyl
      deficient as they had increased intracellular S-adenosylmethionine concentrations
      (132% of control; P < 0.01). Despite increased phosphatidylcholine synthesis via
      sequential methylation of phosphatidylethanol-amine, choline-deficient
      hepatocytes had significantly decreased (P < 0.01) intracellular concentrations
      of choline (20% of control), phosphocholine (6% of control),
      glycerophosphocholine (15% of control), and phosphatidylcholine (55% of control).
      Methyl-supplementation in choline-deficiency enhanced intracellular methyl-group
      availability, but did not correct choline-deficiency induced abnormalities in
      either choline metabolite or phospholipid content in hepatocytes. Methyl
      supplemented, choline-deficient cells died by apoptosis. In a rat study, 2 weeks
      of a choline deficient diet supplemented with betaine did not prevent the
      occurrence of fatty liver and the increased DNA strand breakage induced by
      choline-deficiency. Though dietary supplementation with betaine restored hepatic
      betaine concentration and increased hepatic S-adenosylmethionine/S
      adenosylhomocysteine ratio, it did not correct depleted choline (15% of control),
      phosphocholine (6% control), or phosphatidylcholine (48% of control)
      concentrations in deficient livers. These data show that decreased intracellular
      choline and/or choline metabolite concentrations, and not methyl deficiency, are
      associated with apoptotic death of hepatocytes.

PMID- 9027581
TI  - Cyclosporin A and its non-immunosuppressive derivative exhibit a differential
      effect on cell-mediated mineralization in culture.
AB  - Chronic immunosuppressive treatment with cyclosporin A (CsA) is associated with
      decreased bone density. However, in culture, CsA inhibits osteoclast
      differentiation and bone resorption. This raises the question as to whether CsA
      also affects osteoblast function. Immunophilin, one of the CsA-binding
      cyclophilins that is implicated in the immunosuppressive action of CsA via
      calcineurin, is a peptidyl prolyl cis-trans isomerase (PPl). CsA also binds a
      mitochondrial membrane PPl which is implicated in controlling permeability
      transition pores. Therefore, in the present study we tested the effect of CsA on
      cell mediated mineralization in parallel with mitochondrial rhodamine retention
      as an indicator of mitochondrial membrane potential Rat marrow stromal cells were
      grown in dexamethasone (DEX) medium to stimulate mineralization in culture, and
      CsA was added to various cultures using different treatment schedules. Low dose
      (0.1 microM) CsA inhibited mineralization, compared to controls, when present in
      the cultures during days 3-11 of DEX stimulation. Contrarily, high dose CsA (1.0
      microM) resisted the inhibitory effect of the low dose. SDZ 220-384 (SDZ), a non
      immunosuppressive derivative of CsA which is known, like CsA, to bind to
      mitochondrial cyclophilin but does not inhibit calcineurin, was also tested. Both
      high and low doses of SDZ decreased mineralization when present in the cultures
      from day 3 or from day 0. The similar effect of the low CsA dose and SDZ on
      mineralization is in accord with their ability to block permeability transition
      pores. The differential effect, on day 21 mineralization, between high CsA dose
      and SDZ took place in parallel to their opposing effects on mitochondrial
      membrane potential. On days 4-8, mitochondrial rhodamine retention was higher
      under CsA than under SDZ. Under these conditions there was no significant
      difference between the effects of these drugs on cell proliferation measured on
      day 11; there was a minor decrease in specific alkaline phosphatase activity by
      SDZ, too small to explain the extent of mineralization inhibition by SDZ. These
      results suggest that permeability transition pores might be involved in
      controlling mineralization. Unlike SDZ, CsA exhibits an additional effect on the
      mitochondrial membrane potential and on mineralization when applied at a high
      dose on day 3. Therefore identifying the additional activity of high dose CsA,
      which is missing in SDZ, may be beneficial. Such activity is expected to resist
      changes in rhodamine retention and decreased mineralization induced by SDZ, and
      yet enable preservation of immunosuppressive activity of CsA.

PMID- 9027582
TI  - Isolation, characterization, and chromosomal mapping of a novel cDNA clone
      encoding human selenium binding protein.
AB  - We have isolated the full-length human 56 kDa selenium binding protein (hSP56)
      cDNA clone, which is the human homolog of mouse 56 kDa selenium binding protein.
      The cDNA is 1,668 bp long and has an open reading frame encoding 472 amino acids.
      The calculated molecular weight is 52.25 kDa and the estimated isoelectric point
      is 6.13. Using Northern blot hybridization, we found that this 56 kDa selenium
      binding protein is expressed in mouse heart with an intermediate level between
      those found in liver/lung/kidney and intestine. We have also successfully
      expressed hSP56 in Escherichia coli using the expression vector-pAED4. The hSP56
      gene is located at human chromosome 1q21-22).

PMID- 9027583
TI  - Chloroquine, quinine and quinidine inhibit calcium release from macrophage
      intracellular stores by blocking inositol 1,4,5-trisphosphate binding to its
      receptor.
AB  - The binding of many ligands to cellular receptors induces a signaling cascade
      which generates inositol 1,4,5-trisphosphate (IP3). IP3 binding to its receptors
      in various internal compartments causes a rapid Ca2+ efflux into the cytosol. We
      now demonstrate that chloroquine blocks ligand-induced Ca2+ mobilization without
      affecting IP3 synthesis. The effect is independent of the ligand employed and
      occurred with five unrelated ligands; namely, alpha 2-macroglobulin-methylamine,
      angiotensin II, bradykinin, carbachol, and epidermal growth factor. Chloroquine,
      quinidine, and quinine, however, block binding of [3H]IP3 to its receptors by
      90%, 88%, and 71%, respectively. These observations suggest a previously
      undetected mechanism by which these agents may in part function as antimalarials.

PMID- 9027584
TI  - Protective role of intraperitoneally administrated vitamin E and selenium on the
      levels of total lipid, total cholesterol, and fatty acid composition of muscle
      and liver tissues in rats.
AB  - The aim of this work was to determine the protective effects of intraperitoneally
      administrated vitamin E and Se on total lipid, total cholesterol, and fatty acid
      composition of rat liver and muscle tissues. Total lipid content of muscle tissue
      in Se and combination groups decreased as compared to the control group. However,
      the level of total lipid in the liver tissues was seen to decrease only in the
      combination group (P < 0.05). While the amount of total cholesterol in liver
      tissue was lower (P < 0.05) in the vitamin E and combination groups, the amount
      of total cholesterol in muscle tissue decreased (P < 0.05) in the combination
      group. The amount of linoleic acid in muscle tissue slightly decreased (P <
      0.05), whereas the eicosenoic and eicosatrienoic acid amounts significantly
      increased (P < 0.01, P < 0.001) in the vitamin E group as compared to the control
      group. The amounts of most fatty acid decreased (P < 0.05) in the combination
      group. The proportions of eicosenoic, eicosatrienoic, and total polyunsaturated
      fatty acid (PUFA) within the total fatty acid were higher (P < 0.05) in vitamin E
      group, whereas these fatty acids proportions were lower (P < 0.05) in the Se
      group. Although the proportions of palmitic, linolenic, and total saturated fatty
      acids were low (P < 0.05), oleic and total unsaturated fatty acid proportions
      were higher (P < 0.05) in the combination group than in the control group. The
      amount of palmitic acid and total saturated fatty acid in liver tissue decreased
      (P < 0.01 and P < 0.05, respectively) in the vitamin E and combination groups.
      However, the amount of linoleic acid only decreased (P < 0.05) in the combination
      group. The amount of PUFA was slightly higher (P < 0.05) in vitamin E. The
      proportions of stearic acid and linoleic acid decreased (P < 0.05) both in the Se
      and combination groups. However, the proportions of eicosatrienoic, omega 6, and
      PUFA were slightly higher (P < 0.05) in the vitamin E group, but total saturated
      fatty acid proportion significantly decreased (P < 0.01) in both the vitamin E
      and combination groups. In conclusion, the level of total lipid and cholesterol
      in muscle and liver tissues were reduced by administrating vitamin E and Se
      together. Additionally, the fatty acid synthesis in the muscle and liver tissues
      was decreased by this process. However, it was observed that the protective
      effect of intraperitoneally administrated vitamin E was higher than Se on fatty
      acid composition in muscle and liver tissues.

PMID- 9027585
TI  - Effect of activating and inactivating mutations of Gs- and Gi2-alpha protein
      subunits on growth and differentiation of 3T3-L1 preadipocytes.
AB  - Previous investigations have demonstrated that both Gs- and the Gi-family of GTP
      binding proteins are implicated in differentiation of the 3T3-L1 preadipocyte. In
      order to further analyze the role of Gs alpha vs. Gi2 alpha, which are both
      involved in adenylate cyclase modulation, we transfected undifferentiated 3T3-L1
      cells with two sets of G-protein cDNA: the pZEM vector with either wild type, the
      activating (i.e., GTP-ase inhibiting) R201C-Gs alpha or the inactivating
      G226A(H21a)-Gs alpha point mutations, or the pZIPNeoSV(X) retroviral vector
      constructs containing the Gi2 alpha wild type or the missense mutations R179E-Gi2
      alpha, Q205L-Gi2 alpha, and G204A(H21a)-Gi2 alpha. The activating [R201C]Gs alpha
      mutant did not significantly affect the differentiation process, i.e., increase
      in the steady-state levels of G-protein subunits, gross appearance, or insulin
      elicited deoxy-glucose uptake into 3T3-L1 adipocytes, despite a marked initial
      increase in hormone-elicited adenylate cyclase activity. The [H21a]Gs alpha
      mutant, on the other hand, enhanced the degree of differentiation slightly, as
      evidenced by an augmented production of lipid vesicles and insulin-stimulated
      deoxy-glucose uptake. However, an expected increase in mRNA for hormone-sensitive
      lipase was not seen. Secondly, it appeared that both activating [R179E]Gi2 alpha
      or [Q205L]Gi2 alpha mutants reduced cell doubling time in non-confluent 3T3-L1
      cell cultures, while [H21a]Gi2 alpha slowed proliferation rate. Furthermore, it
      seemed that cell proliferation, as evidenced by thymidine incorporation, ceased
      at a much earlier stage prior to cell confluency when cultures were transfected
      with the [R179E]Gi2 alpha or [Q205L]Gi2 alpha mutants. Upon differentiation with
      insulin, dexamethasone, and iBuMeXan, the following cell characteristics emerged:
      the [R179E]Gi2 alpha and [Q205L]Gi2 alpha mutants consistently enhanced adenylate
      cyclase activation and cAMP accumulation stimulated by isoproterenol and
      corticotropin over controls. Deoxy-glucose uptake was also super-activated by the
      [R179E]Gi2 alpha and [Q205L]Gi2 alpha mutants. Finally, steady-state levels of
      hormone sensitive lipase mRNA were dramatically increased by [R179E]Gi2 alpha and
      [Q205L]Gi2 alpha over differentiated controls. The inactivating [H21a]Gi2 alpha
      mutant obliterated all signs of preadipocyte differentiation. It is concluded
      that Gi2 plays a positive and much more important role than Gs in 3T3-L1
      preadipocyte differentiation. Cyclic AMP appears to play no role in this process.

PMID- 9027586
TI  - Purification and substrate specificity of polydeoxyribonucleotide kinases
      isolated from calf thymus and rat liver.
AB  - Damage to DNA can result in strand breaks with 5'-hydroxyl and 3'-phosphate
      termini. Before DNA polymerases and ligases can rejoin the broken strands, such
      termini have to be restored to 5'-phosphate and 3'-hydroxyl groups.
      Polydeoxynucleotide kinase is an enzyme that may fulfil this function. We have
      purified the kinases from calf thymus and rat liver to near homogeneity. Based on
      SDS-polyacrylamide gel electrophoresis and activity gels, the enzymes from both
      sources are approximately 60-kDa polypeptides. Both enzymes have an acidic pH
      optimum (5.5-6.0) for kinase activity, and similar pl values (8.5-8.6), and a
      specificity for DNA. The calf thymus kinase possesses a 3'-phosphatase activity,
      as has previously been shown for the rat liver enzyme. The minimum size of
      oligonucleotide that can be labelled is 7-8 nucleotides in length, but the
      optimal size appears to be > 18 nucleotides. Comparison of phosphorylation of
      oligo(dA)24 and oligo(dT)24 with oligonucleotides containing a varied nucleotide
      sequence indicated that the homopolymers are poorer substrates. Unlike the
      bacteriophage T4 polynucleotide kinase, the mammalian kinases exhibit no
      preference for 5'-overhanging termini when acting at DNA termini produced by
      restriction enzymes. With double-stranded oligonucleotide complexes designed to
      mode single-strand gaps and nicks, the mammalian kinases preferentially
      phosphorylate the 5'-terminus associated with the gap or nick, in keeping with
      the idea that the kinases are involved in the repair of DNA single-strand breaks.

PMID- 9027587
TI  - Peripheral benzodiazepine receptors in isolated human pancreatic islets.
AB  - Peripheral benzodiazepine receptors have been shown in some endocrine tissues,
      namely the testis, the adrenal gland, and the pituitary gland. In this work we
      evaluated whether peripheral benzodiazepine receptors can be found in the
      purified human pancreatic islets and whether they may have a role in insulin
      release. Binding of the isoquinoline compound [3H]1-(2-chlorophenyl-N-methyl-1
      methyl-propyl)-3- isoquinolinecarboxamide (13H]PK-11195) a specific ligand of
      peripheral benzodiazepine receptors, to cellular membranes was saturable and
      Scatchard's analysis of the saturation curve demonstrated the presence of a
      single population of binding sites, with an affinity constant value of 9.20 +/-
      0.80 nM and a maximum number of binding sites value of 8913 +/- 750 fmol/mg of
      proteins. PK-11195 and 7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4-
      benzodiazepine-2-on (Ro 5-4864) significantly potentiated insulin secretion from
      freshly isolated human islets at 3.3 mM glucose. These results show the presence
      of peripheral benzodiazepine receptors in purified human pancreatic islets and
      suggest their role in the mechanisms of insulin release.

PMID- 9027588
TI  - Growth kinetics, self-renewal, and the osteogenic potential of purified human
      mesenchymal stem cells during extensive subcultivation and following
      cryopreservation.
AB  - Recent studies have demonstrated the existence of a subset of cells in human bone
      marrow capable of differentiating along multiple mesenchymal lineages. Not only
      do these mesenchymal stem cells (MSCs) possess multilineage developmental
      potential, but they may be cultured ex vivo for many passages without overt
      expression of a differentiated phenotype. The goals of the current study were to
      determine the growth kinetics, self-renewing capacity and the osteogenic
      potential of purified MSCs during extensive subcultivation and following
      cryopreservation. Primary cultures of MSCs were established from normal iliac
      crest bone marrow aspirates, an aliquot was cryopreserved and thawed, and then
      both frozen and unfrozen populations were subcultivated in parallel for as many
      as 15 passages. Cells derived from each passage were assayed for their kinetics
      of growth and their osteogenic potential in response to an osteoinductive medium
      containing dexamethasone. Spindle-shaped human MSCs in primary culture exhibit a
      lag phase of growth, followed by a log phase, finally resulting in a growth
      plateau state. Passaged cultures proceed through the same stages, however, the
      rate of growth in log phase and the final number of cells after a fixed period in
      culture diminishes as a function of continued passaging. The average number of
      population doublings for marrow-derived adult human MSCs was determined to be 38
      +/- 4, at which time the cells finally became very broad and flattened before
      degenerating. The osteogenic potential of cells was conserved throughout every
      passage as evidenced by the significant increase in APase activity and formation
      of mineralized nodular aggregates. Furthermore, the process of cryopreserving and
      thawing the cells had no effect on either their growth or osteogenic
      differentiation. Importantly, these studies demonstrate that replicative
      senescence of MSCs is not a state of terminal differentiation since these cells
      remain capable of progressing through the osteogenic lineage. The use of
      population doubling potential as a measure of biological age suggests that MSCs
      are intermediately between embryonic and adult tissues, and as such, may provide
      an in situ source for mesenchymal progenitor cells throughout an adult's
      lifetime.

PMID- 9027590
TI  - C-myc deregulation during transformation induction: involvement of 7SK RNA.
AB  - The process of oncogenic transformation has been widely studied but is still
      poorly understood. We have focused on the mechanism of deregulation of the c-myc
      gene during transformation of a temperature-sensitive SV40-transformed mouse cell
      line. Run-on transcription assays showed that the two c-myc minor promoters, P1
      and P3, are transiently activated following induction of transformation and that
      peak activation of both promoters is preceded by a large increase in
      transcription of a small RNA (7SK). To test the possibility that this RNA might
      participate in promoter activation, we transfected cells with sense and antisense
      oligodeoxynucleotides corresponding to different regions of the 7SK RNA predicted
      to be accessible within the RNP particle. Out of 14 oligos tested, inhibition of
      activation of P1 and/or P3 was observed with four antisense oligonucleotides
      corresponding to looped regions in the putative 7SK secondary structure. To
      identify c-myc promoter sequences which might serve as targets for 7SK activity,
      we carried out mobility-shift assays with either whole or 7SK-depleted cell
      extracts. The CT element of the c-myc promoter formed a 7SK-dependent complex
      which could be competed only with the same antisense 7SK oligo that suppressed P1
      and P3 activation in vivo. Taken together these results suggest that 7SK RNP
      participates in transformation-dependent c-myc deregulation.

PMID- 9027589
TI  - Osteogenic differentiation of purified, culture-expanded human mesenchymal stem
      cells in vitro.
AB  - Human bone marrow contains a population of cells capable of differentiating along
      multiple mesenchymal cell lineages. Recently, techniques for the purification and
      culture-expansion of these human marrow-derived Mesenchymal Stem Cells (MSCs)
      have been developed. The goals of the current study were to establish a
      reproducible system for the in vitro osteogenic differentiation of human MSCs,
      and to characterize the effect of changes in the microenvironment upon the
      process. MSCs derived from 2nd or 3rd passage were cultured for 16 days in
      various base media containing 1 to 1000 nM dexamethasone (Dex), 0.01 to 4 mM L
      ascorbic acid-2-phosphate (AsAP) or 0.25 mM ascorbic acid, and 1 to 10 mM beta
      glycerophosphate (beta GP). Optimal osteogenic differentiation, as determined by
      osteoblastic morphology, expression of alkaline phosphatase (APase), reactivity
      with anti-osteogenic cell surface monoclonal antibodies, modulation of
      osteocalcin mRNA production, and the formation of a mineralized extracellular
      matrix containing hydroxyapatite was achieved with DMEM base medium plus 100 nM
      Dex, 0.05 mM AsAP, and 10 mM beta GP. The formation of a continuously
      interconnected network of APase-positive cells and mineralized matrix supports
      the characterization of this progenitor population as homogeneous. While higher
      initial seeding densities did not affect cell number of APase activity,
      significantly more mineral was deposited in these cultures, suggesting that
      events which occur early in the differentiation process are linked to end-stage
      phenotypic expression. Furthermore, cultures allowed to concentrate their soluble
      products in the media produced more mineralized matrix, thereby implying a role
      for autocrine or paracrine factors synthesized by human MSCs undergoing
      osteoblastic lineage progression. This culture system is responsive to subtle
      manipulations including the basal nutrient medium, dose of physiologic
      supplements, cell seeding density, and volume of tissue culture medium. Cultured
      human MSCs provide a useful model for evaluating the multiple factors responsible
      for the step-wise progression of cells from undifferentiated precursors to
      secretory osteoblasts, and eventually terminally differentiated osteocytes.

PMID- 9027591
TI  - Functional analysis of the lysyl oxidase promoter in myofibroblast-like clones of
      3T6 fibroblast.
AB  - Lysyl oxidase (LO), an extracellular enzyme catalysing the first step of collagen
      and elastin cross-linking, is transiently expressed by myofibroblasts during
      fibrosis. A cell model with features of myofibroblast was thus established for
      studying the regulation of LO. Two clones of the 3T6 fibroblast cell line were
      selected because 1) they produced a relatively high steady-state level of the
      three lysyl oxidase mRNAs with the same relative ratio similar to fibrotic tissue
      and 2) they stably displayed certain features of myofibroblast (alpha-smooth
      muscle actin cytoskeleton, bundles of cytoskeletal filaments beneath the
      cytoplasmic membranes). These clones synthesized predominantly type I collagen
      fibers and a small amount of type III collagen. Neither type IV collagen nor
      elastin were observed. The cloning and sequencing of 2,073 bp of the mouse Balb/C
      LO promoter was performed, allowing the identification around the initiation of
      transcription of consensus sequences which are found on the COL1 promoters. A
      series of deletion constructs containing the LO 5'-flanking region ligated to the
      luciferase gene were transiently transfected into 3T6-5 fibroblasts. The region
      allowing the maximal activity was found between positions -416 to -192, while the
      more upstream region negatively regulated the promoter. The -898 to -865 sequence
      (called LOcol1) displayed 79% of homology with a conserved sequence of murine,
      rat, and human COL1A1 promoters. This sequence participated to the binding of
      several nuclear factors within a region (-970 to -784) allowing 50% of inhibition
      of the LO promoter. Therefore, the level of LO transcription is regulated in 3T6
      5 fibroblast by positive and negative cis-acting regulatory elements which might
      have common features with the COL1A1 promoter.

PMID- 9027592
TI  - Risk biomarkers and current strategies for cancer chemoprevention.
AB  - Quantifiable, well-characterized cancer risk factors demonstrate the need for
      chemoprevention and define cohorts for chemopreventive intervention. For
      chemoprevention, the important cancer risk factors are those that can be measured
      quantitatively in the subject at risk. These factors, called risk biomarkers, can
      be used to identify cohorts for chemoprevention. Those modulated by
      chemopreventive agents may also be used as endpoints in chemoprevention studies.
      Generally, the risk biomarkers fit into categories based on those previously
      defined by Hulka: 1) carcinogen exposure, 2) carcinogen exposure/effect, 3)
      genetic predisposition, 4) intermediate biomarkers of cancer, and 5) previous
      cancers. Besides their use in characterizing cohorts for chemoprevention trials,
      some risk biomarkers can be modulated by chemopreventive agents. These biomarkers
      may be suitable surrogate endpoints for cancer incidence in chemoprevention
      intervention trials. The criteria for risk biomarkers defining cohorts and
      serving as endpoints are the same, except that those defining cohorts are not
      necessarily modulated by chemopreventive agents. A primary criterion is that the
      biomarkers fit expected biological mechanisms of early carcinogenesis-i.e.,
      differential expression in normal and high-risk tissue, on or closely linked to
      the causal pathway for the cancer, and short latency compared with cancer. They
      must occur in sufficient number to allow their biological and statistical
      evaluation. Further, the biomarkers should be assayed reliably and
      quantitatively, measured easily, and correlated to cancer incidence. Particularly
      important for cancer risk screening in normal subjects is the ability to use
      noninvasive techniques that are highly specific, sensitive, and quantitative.
      Since carcinogenesis is a multipath process, single biomarkers are difficult to
      correlate to cancer, as they may appear on only one or a few of the many possible
      causal pathways. As shown in colorectal carcinogenesis, the risks associated with
      the presence of biomarkers may be additive or synergistic. That is, the
      accumulation of genetic lesions is the more important determinant of colorectal
      cancer compared with the presence of any single lesion. Thus, batteries of
      biomarker abnormalities, particularly those representing the range of
      carcinogenesis pathways, may prove more useful than single biomarkers both in
      characterizing cohorts at risk and defining modulatable risks. Risk biomarkers
      are already being integrated into many chemoprevention intervention trials. One
      example is the phase II trial of oltipraz inhibition of carcinogen-DNA adducts in
      a Chinese population exposed to aflatoxin B1. Also, urine samples from subjects
      in this trial will be screened for the effect of oltipraz on urinary mutagens. A
      second example is a chemoprevention protocol developed for patients at high risk
      for breast cancer; the cohort is defined both by hereditary risk and the presence
      of biomarker abnormalities. Modulation of the biomarker abnormalities is a
      proposed endpoint. Also, dysplastic lesions, such as prostatic intraepithelial
      neoplasia, oral leukoplakia and colorectal adenomas, have been used to define
      high-risk cohorts and as potential modulatable surrogate endpoints in
      chemoprevention trials.

PMID- 9027593
TI  - Genetic susceptibility to cancer from exogenous and endogenous exposures.
AB  - The past four decades of epidemiological research have yielded valuable
      information on the risks of populations to environmental exposures such as
      tobacco, asbestos, and dietary components. Prevention efforts have been focused
      on large-scale population-based interventions to minimize exposure to such
      external carcinogens. While some cancers are beginning to show a decline from
      changing environmental exposures, hormone-related cancers, such as breast and
      prostate, are becoming more prevalent. The development of these cancers appears
      to be closely related to endogenous exposures to circulating steroid hormones.
      Although prevention trials using antihormone agents are proving successful in
      some instances, the long-term control of these cancers necessitates a clearer
      understanding of the metabolism and transport of the relevant hormone in vivo.
      The revolution in molecular biology has provided powerful genetic tools for
      evaluating mechanisms of cancer causation as well as the potential to better
      define individual susceptibility. Using tobacco exposure as an example, we and
      others have demonstrated that polymorphisms in genes controlling aromatic amine
      metabolism provide at least a partial explanation for ethnic and individual
      susceptibility to bladder cancer. Similar studies have examined genetic
      polymorphisms in the metabolism of tobacco smoke and lung cancer risk, red meat
      and colorectal cancer, and aflatoxin and liver cancer. Our current studies have
      pursued a similar paradigm of genetic polymorphism and individual cancer
      susceptibility in prostate and breast carcinogenesis. We are evaluating
      polymorphisms in the steroid 5 alpha-reductase type II and androgen receptor
      genes in relation to prostate cancer based on the evidence that intracellular
      dihydrotestosterone is the critical "carcinogen." We are pursuing genetic
      polymorphisms affecting estradiol metabolism, including those in the 17 beta
      hydroxysteroid dehydrogenase 2 and estrogen receptor genes as they relate to
      susceptibility to breast cancer. The potential role of a polymorphism in the
      cytochrome P450c 17 alpha gene in both breast and prostate cancers is also being
      examined.

PMID- 9027594
TI  - Relevance of cyclin D1 and other molecular markers to cancer chemoprevention.
AB  - Until recently studies on mutations in cellular genes implicated in multistage
      carcinogenesis have concentrated mainly on dominant acting mutations in cellular
      proto-oncogenes, genes that normally mediate agonist-induced signal transduction
      pathways, and recessive mutations in cellular tumor suppressor genes, whose
      normal products appear to inhibit cell growth and/or control differentiation and
      cell-cell interactions. It seems likely, however, that a third category of
      cellular genes, the cyclins and cyclin-related genes, may also be critical
      targets during multistage carcinogenesis because of the central role that they
      play in controlling cell cycle progression. These proteins could, therefore,
      provide biomarkers for identifying individuals at high risk of developing cancer
      and also serve as novel targets for chemopreventive agents. This paper reviews
      evidence that the gene cyclin D1 is amplified and/or overexpressed in a major
      fraction of human tumors, and that this can occur relatively early in the
      carcinogenic process. Mechanistic studies indicates that this overexpression
      plays a critical role in tumor progression as well as the maintenance of the
      tumorigenic phenotype. Thus, increased cyclin D1 expression can enhance gene
      amplification and cell transformation and antisense to cyclin D1 can revert
      malignant cells. The latter findings provide direct evidence that cyclin D and
      related proteins might be useful markers and also targets for cancer
      chemoprevention.

PMID- 9027596
TI  - Inherited susceptibility and acquired allelic imbalance in rat mammary
      carcinogenesis.
AB  - Individual genetically determined susceptibility to cancer as well as acquired
      epigenetic and genetic organ specific alterations are important considerations in
      choosing target populations for chemopreventive trials. These individual
      epigenetic and genetic alterations can also serve as potential biomarkers for
      chemoprevention clinical trials. In order to model these potential markers for
      chemoprevention investigations, we are examining a series of interrelated rat
      models. Inbred rats vary in their susceptibility to mammary cancer induction by
      environmental agents. For example, the WF strain is highly susceptible to
      chemically induced mammary cancer while the Cop rat is almost completely
      resistant. The F344 is intermediate in susceptibility to chemically induced
      mammary cancer. These differential susceptibilities are inherited in a dominant
      pattern. For example, resistance is due to the inheritance of Mcs gene(s) which
      likely act by altering the differentiation lineage of mammary epithelial cells.
      As tumors form in the mammary glands of these rats, they acquire additional
      epigenetic and genetic alterations. Epigenetic initiation is a very frequent
      cellular event following carcinogen exposure which may predispose cells to
      genetic change including allelic imbalance. For example, following a standard
      dose of NMU or DMBA over 1% of cells are epigenetically initiated. During the
      carcinogenesis process, initiated cells may acquire genetic change such as
      oncogene activation and allelic imbalance. Interestingly, the pattern of allelic
      imbalance appears to be an inherited trait. For example, a non-random loss of
      heterozygosity (LOH) in rat chromosome 1 following DMBA only occurs in certain
      strains, such as Cop rats. Interestingly this change does not occur following
      initiation by ionizing radiation. It will thus be important to identify these
      epigenetic and genetic events which underlie mammary carcinogenesis as well as
      determine their patterns of inherited predisposition and temporal occurrence.
      Such knowledge is critical if we are to develop new molecular markers for
      chemoprevention trials.

PMID- 9027595
TI  - Cancer risk factors for selecting cohorts for large-scale chemoprevention trials.
AB  - Many anticipate that application of findings in molecular genetics will help to
      achieve greater precision in defining high-risk populations that may benefit from
      chemopreventive interventions. We must recognize, however, that genetic
      susceptibility, environmental factors, and complex gene-environment interactions
      are all likely to be risk determinants for most cancers. Cohort studies of twins
      and cancer indicate that having "identical" genes is generally not a very
      accurate predictor of cancer incidence. Data from twin studies support the
      suggestion that environmental factors such as tobacco use significantly influence
      cancer risk. The complexities of the genetic contribution to disease risk are
      exemplified by the development of Duchenne muscular dystrophy in only one of
      monozygotic twin girls, hypothesized to be the result of X chromosome
      inactivation, with the distribution patterns of the X chromosome being skewed to
      the female X in the manifesting twin and to the male X in the normal twin.
      Evidence from transgenic and genetic-environmental studies in animals support the
      possibility of genetic-environmental interactions. Calorie restriction modifies
      tumor expression in p53 knockout mice; a high-fat, low-calcium, low-vitamin D
      diet increases prepolyp hyperplasia formation in Apc-mutated mice; and calorie
      restriction early in life influences development of obesity in the genetically
      obese Zucker rat (fafa). Such environmental modulation of gene expression
      suggests that chemoprevention has the potential to reduce risk for both
      environmentally and genetically determined cancers. In view of the growing
      research efforts in chemoprevention, the NCI has developed a Prevention Trials
      Decision Network (PTDN) to formalize the evaluation and approval process for
      large-scale chemoprevention trials. The PTDN addresses large trial prioritization
      and the associated issues of minority recruitment and retention; identification
      and validation of biomarkers as intermediate endpoints for cancer; and
      chemopreventive agent selection and development. A comprehensive database is
      being established to support the PTDN's decision-making process and will help to
      determine which agents investigated in preclinical and early phase clinical
      trials should move to large-scale testing. Cohorts for large-scale
      chemoprevention trials include individuals who are determined to be at high risk
      as a result of genetic predisposition, carcinogenic exposure, or the presence of
      biomarkers indicative of increased risk. Current large-scale trials in well
      defined, high-risk populations include the Breast Cancer Prevention Trial
      (tamoxifen), the Prostate Cancer Prevention Trial (finasteride), and the N-(4
      hydroxyphenyl) retinamide (4-HPR) breast cancer prevention study being conducted
      in Milan. Biomarker studies will provide valuable information for refining the
      design and facilitating the implementation of future large-scale trials. For
      example, potential biomarkers are being assessed at biopsy in women with ductal
      carcinoma in situ (DCIS). The women are then randomized to either placebo,
      tamoxifen, 4-HPR, or tamoxifen plus 4-HPR for 2-4 weeks, at which time surgery is
      performed and the biomarkers reassessed to determine biomarker modulation by the
      interventions. For prostate cancer, modulation of prostatic intraepithelial
      neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated;
      similar studies are being planned for oltipraz, dehydroepiandrosterone, and
      vitamin E plus selenomethionine. The validation of biomarkers as surrogate
      endpoints for cancer incidence in high-risk cohorts will allow more agents to be
      evaluated in shorter studies that use fewer subjects to achieve the desired
      statistical power.

PMID- 9027597
TI  - Detection of genomic alterations in human cervical cancer by two-dimensional gel
      electrophoresis.
AB  - Two-dimensional gel electrophoresis was used to comprehensively scan the whole
      genome of 6 cervical intraepithelial neoplasia (CIN) lesions, 7 cervical squamous
      cell carcinomas, 1 cervical adenosquamous cell carcinoma, and 2 cervical
      adenocarcinomas for multiple genetic alterations, such as DNA amplification,
      chromosome deletion, loss of heterozygosity, and chromosome translocation, as
      compared with the paired normal tissues. DNA spot analysis of the genomic 2
      dimensional gels was performed by a computer color overlay system and by spot
      recognition software allowing for objective spot comparison and quantitation.
      Nine spots were found to be amplified in the cervical carcinomas while two
      amplified spots were detected in the CIN III lesions. Fourteen DNA spots were
      either reduced in their intensity or absent in cervical carcinomas as compared to
      their normal paired tissues. Reduction of intensity in 6 spots was observed in
      the 5 CIN III lesions. These genetic alterations may represent changes in cancer
      genes that are associated with human cervical carcinogenesis. Further
      characterization of these alterations may be significant to the understanding of
      cervical tumorigenesis and to the development of biomarkers for clinical trials
      in cancer chemoprevention.

PMID- 9027598
TI  - DNA quantification in cervical intraepithelial neoplasia thick tissue sections by
      confocal laser scanning microscopy.
AB  - Image analysis of tissue biopsies for determination of DNA content as an early
      marker of neoplasia is hampered by the complexity of corrections necessary to dea
      with nuclear truncation and overlap in thin sections. The use of confocal laser
      scanning microscopy (CLSM) for measurement of cellular DNA content on whole cells
      within thick tissue sections offers the advantage of preservation of cellular
      architecture, capacity for 3-dimensional analysis, and absence of sectioning
      artifacts. We have applied this technique to pararosaniline-Feulgen stained human
      cervical tissues graded from normal to cervical intraepithelial neoplasia (CIN)
      III. For the purpose of comparison, 15 microns sections were stained and mapped
      so that the same cell population could be analyzed by both integrated optical
      density and fluorescence intensity. Distribution of DNA content from normal
      cervical epithelial cells 2-3 layers out from the basal cell layer measured by
      both methodologies showed a stable G0/G1 population with no observable S-phase or
      G2 cells. Cells measured from areas of increasing CIN grade showed progressively
      higher DNA content values that were not observable in normal tissue. Although
      these data are preliminary they suggest that CLSM can be used to identify
      aneuploid states within defined structural areas of pre-invasive neoplasia.

PMID- 9027599
TI  - Detection of chromosome instability of tissue fields at risk: in situ
      hybridization.
AB  - Many human tumors are thought to develop along a multistep pathway in tissues
      that have encountered long periods of carcinogen exposure and thus have
      accumulated genetic hits in functional targets relevant to tumor evolution. The
      cumulative degree of genetic change is dependent on both exogenous (e.g., degree
      of carcinogen exposure) and endogenous factors (e.g., metabolism of
      procarcinogens, repair or misrepair capacity, proliferation properties of the
      tissue, capability of damaged cells to survive). Thus one approach to risk
      estimation is to measure the accumulated amount of genetic damage in a target
      tissue at risk for tumor development. Since one cannot predict the exact site of
      the future tumor, the risk assay must detect a generalized ongoing process of
      genetic instability from small, random biopsies. The technique of chromosome in
      situ hybridization involves the use of chromosome- or region-specific probes and
      provides an ability to directly visualize genetic change (e.g., random or clonal
      chromosome polysomy and monosomy) on thin tissue sections (where tissue
      architecture is maintained) or exfoliated cells. Analyses of normal and
      premalignant lesions adjacent to tumors (e.g., head and neck, lung, bladder,
      cervix, breast) have demonstrated that chromosome instability can be detected in
      the field of the tumor (i.e., in normal and premalignant cells in a tissue at
      100% risk of tumor development) and the degree of chromosome instability
      increases with the degree of histologic progression toward cancer. Analyses of
      premalignant lesions (e.g., oral leukoplakia and erythroplakia from individuals
      at risk for aerodigestive tract cancer) by chromosome in situ hybridization have
      uncovered varying degrees of chromosome instability. However, approximately half
      of those individuals who showed a high degree of chromosome instability in
      biopsies subsequently developed aerodigestive tract cancer. Of interest, half of
      these tumors have developed away from the biopsied site, suggesting that the
      detection of a chromosome instability process in one aspect of the tissue might
      yield risk information for the total tissue field. These studies also suggest
      that chromosome in situ hybridization might be useful for identifying individuals
      with high tumor risk who might benefit from chemopreventive intervention.

PMID- 9027600
TI  - Application of molecular epidemiology to lung cancer chemoprevention.
AB  - Molecular epidemiology has made great progress in detecting and documenting
      carcinogenic exposures and host susceptibility factors, in an effort to explain
      interindividual variation in disease. Interindividual differences in cancer risk
      have been hypothesized to result from an array of both genetic and acquired
      factors including nutritional status. Elevated risk of lung cancer has been
      associated with polymorphisms of metabolic genes such as CYP1A1 and GSTM1. On the
      other hand, numerous studies have demonstrated that diets rich in fruits and
      vegetables are protective against cancer, and have correlated high levels of
      antioxidants in the blood with decreased risk. As a first step in identifying
      susceptible individuals, we have assessed the combined effect of genetic factors
      and nutritional status on DNA adducts in a population of healthy smokers. Plasma
      retinol, beta-carotene, alpha-tocopherol, and zeaxanthin were inversely
      correlated with DNA damage, especially in subjects lacking the "protective" GSTM1
      gene. Research is ongoing using biomarkers to determine the effect of
      supplementation with antioxidants/vitamins on DNA damage, especially in
      population subsets with putative "at risk" genotypes. Information on mechanisms
      of interactions between exposure, micronutrients, and other susceptibility
      factors is important in the development of effective practical interventions.

PMID- 9027601
TI  - Defining and analyzing cohorts using molecular markers of cancer risk.
AB  - Cancer is currently regarded to be the phenotypic expression of an accumulation
      of heritable alterations in the regulators of cell growth and differentiation.
      Though detailed knowledge of the sequence and in vivo mechanistic effects of
      these alterations is rudimentary for most, if not all, cancers, their
      identification does offer the potential for classifying groups of individuals who
      are heterogeneous with respect to their cancer risks, into more nearly
      homogeneous subgroups. In this paper, we illustrate the value of using markers,
      which we define as any manifestation of cellular molecular diversity, to increase
      subgroup homogeneity. In the context of time-to-event data, we demonstrate for
      both somatic mutations (acquired p53 abnormalities in gastric mucosal cells) and
      inherited polymorphisms (polymorphisms in the phase 1 and 2 detoxifying enzymes)
      how knowledge regarding the population frequency of the marker the effect of the
      marker on the risk of cancer development, and/or the effect of the marker on
      response to therapy, can be used to plan and analyze such trials. Using as
      paradigms demographic features of the recently begun Shandong precancerous
      gastric lesion intervention trial, and the recently completed alpha-tocopherol
      beta-carotene (ATBC) lung cancer prevention study, we review the information,
      assumptions, and mathematical structure required for planning cancer prevention
      trials. We graphically demonstrate how informative markers make available
      strategies for selection, stratification, and optimal weighing, which, when
      properly implemented, increase the power of tests of effective cancer prevention
      agents.

PMID- 9027602
TI  - Mutagen sensitivity as a marker of cancer susceptibility.
AB  - Modulation of environmental exposures by host genetic factors may explain
      interindividual variation in susceptibility to carcinogenesis. One determinant of
      susceptibility is mutagen sensitivity measured by the frequency of bleomycin
      induced breaks in an in vitro lymphocyte assay. Mutagen sensitivity is a
      significant predictor of aerodigestive tract cancer risk. In this case-control
      study of lung-cancer susceptibility markers, 54% of 132 lung-cancer cases had
      mutagen-sensitivity scores greater than or equal to 1 break/cell, compared with
      only 22% of 232 controls. The mean breaks/cell value (+/-SE) for the 88 African
      American cases was 1.11 (+/-0.60), compared with 0.82 (+/-0.49) for the 121
      controls (P < 0.001). For the 44 Mexican-American cases and 111 controls, the
      comparable values were 1.11 (+/-0.52) and 0.76 (+/-0.38), respectively. The
      overall odds ratio (OR) for mutagen sensitivity (dichotomized at > or = 1
      break/cell), after adjusting for ethnicity and smoking status, was 3.62 (95%
      confidence limits [CL] = 2.2, 5.9). For current smokers the adjusted risk
      associated with mutagen sensitivity was 2.52 (1.2, 5.3). For former smokers, the
      comparable OR (95% CL) was 6.19 (2.7, 14.1). The risk estimate for those under 61
      years of age was 4.85 (2.3, 10.4), compared with 2.85 (1.5, 5.6) for older
      subjects. The risk also appeared to be higher for lighter smokers (< 20
      cigarettes daily) than heavier smokers (ORs = 5.72 and 3.20, respectively). The
      ethnicity-adjusted ORs by quartile of breaks/cell were 1.0, 1.40, 2.46, and 4.80;
      the trend test was significant at P < 0.001. The joint effects of mutagen
      sensitivity and former smoking, current smoking, or heavy smoking were greater
      than additive, although the interaction terms were not statistically significant
      in the logistic model. Mutagen sensitivity may therefore be a useful member of a
      panel of susceptibility markers for defining high-risk subgroups for
      chemoprevention trials.

PMID- 9027603
TI  - Carcinogen-DNA and protein adducts: biomarkers for cohort selection and
      modifiable endpoints in chemoprevention trials.
AB  - Chemical-specific markers have been developed for a number of environmental
      carcinogens for use as molecular dosimeters of individual exposure. In addition
      to contributing substantially to the specificity and sensitivity of
      epidemiological studies aimed at determining the role of environmental agents in
      the etiology of human cancers, some of these biomarkers may prove to be useful
      endpoints for assessing the efficacy of preventive interventions including
      exposure avoidance or remediation and chemoprevention. Biomarkers of the
      biologically effective dose may be particularly useful in this context in that
      they provide a mechanistic linkage between exposure and disease outcome. The
      biologically effective dose reflects the amount of toxicant that has interacted
      with its critical molecular target and can be measured through a variety of
      analytical techniques as either carcinogen-DNA or -protein adducts. Approaches
      for the development and validation of aflatoxin adduct biomarkers are presented
      as a paradigm for the application of carcinogen-specific markers for cohort
      selection and as modifiable endpoints for assessing efficacy in chemoprevention
      trials.

PMID- 9027604
TI  - Smokers and urinary genotoxins: implications for selection of cohorts and
      modulation of endpoints in chemoprevention trials.
AB  - Urinary genotoxicity assays measure the internal dose of genotoxic carcinogens,
      thereby providing a particularly sensitive endpoint for selecting cohorts of
      individuals exposed to cigarette smoke or other mutagens excreted with urines, as
      well as for evaluating the modulation of this parameter after administration of
      chemopreventive agents. Mutagenicity of urines was investigated in smoking
      Italian volunteers, who received oral N-acetylcysteine (NAC) at the same doses
      which are usually prescribed for the long-term treatment of chronic bronchitis.
      The daily excretion of mutagens, concentrated on XAD-2 columns and tested in
      Salmonella typhimurium YG1024 with S9 mix, was significantly and remarkably
      decreased by NAC in the majority of the subjects examined so far. Time-course
      experiments showed that this effect starts since the first day of drug
      administration and reverses when treatment is withdrawn. In addition, NAC
      administration almost totally prevented urinary genotoxicity in one subject whose
      concentrated urines induced a differential lethality in Escherichia coli strains
      having distinctive DNA repair capacities. The decrease of urinary genotoxicity
      produced by NAC in the majority of smokers correlates with the ability of this
      thiol to prevent tumors and to affect a variety of intermediate biomarkers in
      animal models. Modulation of the urinary excretion of mutagens is one of the
      biomarkers evaluated in two ongoing Phase II chemoprevention trials. One study
      involves the oral administration of NAC in Dutch smokers. The pretreatment urine
      samples of all the subjects so far recruited are clearly mutagenic. The other
      study involves the oral administration of the dithiolethione oltipraz to
      individuals living in the Qidong County of the People's Republic of China, an
      area of high endemy for HBV infection and of high exposure to aflatoxins.
      Additionally, a large proportion of the recruited male subjects are smokers. A
      total of 500 urine specimens will be assayed from 240 subjects according to a
      complex protocol arranged in three consecutive phases.

PMID- 9027605
TI  - Mutational specificity and cancer chemoprevention.
AB  - Mutational specificity describes the composite of all of the genetic alterations
      in a collection of mutations arising from a specific treatment. The information
      includes not only the nature of the genetic change (e.g., a base substitution or
      a frameshift), but also information about nucleotide position and hence the DNA
      context. As both the type of DNA damage and its position can be expected to
      reflect the nature of the chemical and physical mutagen, mutational specificity
      can be expected to provide insights into mechanisms of mutation. Conversely,
      mutational spectra should also provide insights into the identity of the mutagen.
      Indeed, the pioneering work on mutational specificity in Escherichia coli
      indicates that each physical or chemical treatment produces a unique spectrum of
      mutations. With the application of biotechnology to the field of genotoxicology,
      the database of sequenced mutations has become quite substantial. Both in vitro
      and in vivo data has been obtained following exposure to a variety of agents. In
      this communication we will critically assess whether the reality of mutational
      specificity has fulfilled the expectations and to examine what potential remains
      to be explored, especially in the area of monitoring human populations. The
      usefulness of both mutational spectra analysis and population monitoring with
      regards to chemoprevention are discussed.

PMID- 9027606
TI  - Classification of duct carcinoma in situ (DCIS) with a characterization of high
      grade lesions: defining cohorts for chemoprevention trials.
AB  - In the last 6 years a number of non-randomized, predominantly single
      institutional trials of breast conservation therapy (BCT) with DCIS, have
      demonstrated that it constitutes a very heterogeneous group of diseases with
      markedly different risks of local recurrence and invasive transformation. There
      has been a consensus that DCIS, which exhibits a "comedo" morphology, generally
      defines a high risk group. Most studies, moreover, have identified the same two
      features, nuclear grade and necrosis, as contributing most significantly to
      prognosis. Nuclear grade and necrosis have been identified as independent
      prognostic variables in several studies. High nuclear grade DCIS which exhibits
      comedo necrosis defines the majority of all DCIS which will result in local
      recurrence and invasive transformation after BCT. Studies utilizing image
      cytometry, to determine ploidy and S-phase fraction and immunohistochemical
      studies of proliferation and oncogene distribution have shown a significant
      association with morphologically identified high nuclear grade and aneuploidy,
      high S-phase fraction or proliferation rate, presence of HER-2/neu and P53
      oncogenes and absence of estrogen receptors. Generally the inverse of this
      association is seen with low nuclear grade DCIS. However, initial hopes that
      these adjunctive studies would identify subsets within the high nuclear grade
      group which might be more likely to recur have not been fulfilled.

PMID- 9027607
TI  - Identification of a chemoprevention cohort from a population of women at high
      risk for breast cancer.
AB  - In a prospective pilot study, we performed breast fine needle aspirations (FNAs)
      on 213 high-risk and 30 low-risk women and analyzed these aspirates for cytologic
      changes and biomarker abnormalities of aneuploidy and overexpressed estrogen
      receptor (ER), epidermal growth factor receptor (EGFR), p53 and HER-2/neu. High
      risk women were those with a first degree relative with breast cancer (73%),
      prior biopsy indicating premalignant breast disease (26%), a history of breast
      cancer (13%), or some multiple of these risk factors (11%). Median ages of the
      high-risk and low-risk groups were 44 and 42, respectively. Sixty-three percent
      of the high-risk and 73% of the low-risk group were premenopausal. Sixty-eight
      percent of the high-risk and 17% of low-risk women had cytologic evidence of
      hyperplasia with or without atypia (P < .0001). Aneuploidy and overexpression of
      EGFR and p53 occurred in 25%, 36%, and 28% of high-risk subjects but in less than
      4% of low-risk subjects (P < .0002). Overexpression of ER and HER-2/neu occurred
      in 8% and 19%, respectively of high-risk women; nc low-risk women had these
      abnormalities. Sixty-eight percent of high-risk women and 7% of low-risk women
      had abnormalities of one or more of these biomarkers exclusive of cytology.
      Thirty-one percent of high-risk women, but no low-risk women had abnormalities of
      two or more biomarkers (P = .0004). Biomarker abnormalities were more frequent
      with increasing cytologic abnormality. Eighteen percent of women with normal
      cytology, 29% of women with epithelial hyperplasia and 60% of women with
      hyperplasia with atypia had abnormalities of two or more biomarkers (P = .048 and
      < .0001, respectively). Restricting the analysis to those three biomarkers most
      frequently overexpressed in the high-risk group (ploidy, EGFR, p53), 13% of high
      risk women with normal cytology, 20% of high-risk women with epithelial
      hyperplasia and 51% of high-risk women with atypical hyperplasia had
      abnormalities of 2 or more of these 3 biomarkers. At a median follow up of two
      years, 8 of 213 women have been diagnosed with in situ (n = 5) or invasive (n =
      3) cancer. Later detection of neoplasia was associated with prior FNA evidence of
      atypical hyperplasia (P < .0001) and multiple biomarker abnormalities in the 5
      test battery (P = .006) by univariate analysis. By multivariate analysis,
      development and/or detection of cancer was primarily predicted by atypical
      hyperplasia (P = .0047) and secondarily by multiple biomarker abnormalities (P =
      0.021). Atypical hyperplasia, EGFR, and p53 in breast FNAs have promise as risk
      markers and as surrogate endpoint biomarkers for breast cancer chemoprevention
      trials.

PMID- 9027608
TI  - Ethical and scientific considerations for chemoprevention research in cohorts at
      genetic risk for breast cancer.
AB  - Identification of cohorts at genetic risk for cancer offers unique research
      opportunities to explore the steps in carcinogenesis, from the inheritance of a
      predisposing mutation to the development of preinvasive lesions or overt
      malignancy, and to evaluate interventions to modulate the carcinogenic process.
      However, cancer prevention strategies for most inherited cancer predisposition
      syndromes are of unproven benefit, and the potential for adverse psychosocial
      effects and employment or insurance discrimination associated with genetic
      testing is substantial. Thus testing for genetic cancer risk remains highly
      controversial, and the National Center for Human Genome Research and the American
      Society of Human Genetics advise DNA testing for presymptomatic identification of
      cancer risk only in the setting of a carefully monitored research environment.
      The commercial availability of predictive genetic testing, particularly for
      inherited susceptibility to cancer, has focused attention not only on the urgent
      need for research in cancer prevention for cohorts at genetic cancer risk but
      also on ethical considerations surrounding clinical prevention research in
      genetic risk groups. This paper addresses the interrelationship of ethical and
      scientific issues in conducting chemoprevention research in these cohorts,
      especially for those studies which require presymptomatic testing for specific
      gene mutations as a study entry criterion or as a criterion for stratification.
      Practical approaches to study design and implementation issues for
      chemoprevention research in genetic risk cohorts are discussed, emphasizing the
      interactions of ethical and scientific considerations at all levels of the
      research process.

PMID- 9027609
TI  - Cohorts with familial disposition for colon cancers in chemoprevention trials.
AB  - Colon cancer provides an attractive setting for chemoprevention trials because of
      the frequency and variation of familial predisposition that is observed in this
      malignancy. Additionally, the adenomatous polyp, the precursor of colon cancer,
      is a valuable intermediate marker for judging the effectiveness of candidate
      chemopreventive agents. Inherited colon cancer susceptibility varies from mild to
      severe. Conditions with extreme susceptibility include the autosomal dominantly
      inherited syndromes of familial adenomatous polyposis (FAP) and hereditary
      nonpolyposis colorectal cancer (HNPCC). These are highly penetrant syndromes with
      extreme cancer risk. FAP arises from mutations of the APC gene and HNPCC from
      mutations of the mismatch repair genes. Specific and individual genetic diagnosis
      is now possible in both syndromes, thus allowing identification of genetically
      affected individuals for chemoprevention trials. FAP accounts for less than 1% of
      colon cancers, while HNPCC may be present in up to 5% of cases. Familial
      clustering is common in the remainder of cases, which are often referred to as
      sporadic, but probably arise in part from inherited susceptibility. Epidemiologic
      studies have shown that first-degree relatives have a two- to four-fold increased
      risk of acquiring colon cancer compared to the general population. Ten percent of
      individuals in the U.S. have a first-degree with colon cancer. This clinically
      identifiable higher risk group thus constitutes a large potential cohort for
      chemoprevention trials. The common familial cases of colon cancer can be further
      stratified by severity. A relative diagnosed under the age of 50 or two first
      degree relatives affected with colon cancer confers an even greater risk for this
      malignancy, estimated to be four to six times that of the general population.
      Adenomatous polyps also precede the development of colon cancer in these
      categories, thereby providing a readily identifiable clinical endpoint to judge
      the effectiveness of chemoprevention. It is expected that genetic markers will
      soon be available for more precise identification of common colon cancer
      susceptibility. Candidate markers include mild mutations of the APC and mismatch
      repair genes, glutathione transferase isoenzymes, acetylator status, and
      phospholipase A2 expression. Bile acid concentrations of the bowel may be
      genetically and/or environmentally determined and likely have a role in colon
      cancer susceptibility. We recently identified a large kindred with polyp and
      cancer susceptibility arising from a mild mutation of the APC gene. There are
      over 4,000 kindred members and mutational testing has demonstrated 140 gene
      carriers to date. We expect to institute chemoprevention trials in this kindred
      using adenomatous polyp number as an endpoint of effectiveness.

PMID- 9027610
TI  - Inherited and acquired risk factors in colonic neoplasia and modulation by
      chemopreventive interventions.
AB  - The progressively abnormal development of epithelial cells prior to tumor
      development leads to widely differing chemopreventive approaches. The diversity
      of these approaches has resulted in different assays to measure the activities of
      the agents. To apply these assays to preclinical studies, we have developed
      rodent models in which different stages of evolution of colonic neoplasia are
      expressed. In one model mice carrying a truncated Apc allele with a nonsense
      mutation in exon 15 have been generated by gene targeting and embryonic stem cell
      technology (Apc 1638 mice). These mice develop multiple gastrointestinal lesions
      including adenomas and carcinomas, focal areas of high grade dysplasia (FAD) and
      polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has
      now been modulated by a chemopreventive regimen. Colonic lesions significantly
      increased in Apc 1638 mice on a Western-style diet, compared to Apc 1638 mice on
      AIN-76A diet which has lower fat content and higher calcium and vitamin D. These
      studies have also been carried out in normal mice, and have demonstrated without
      any chemical carcinogen that a Western-style diet induced colonic tumorigenesis.
      Modulation of cell proliferation has also been induced by Western-style diets in
      other organs including mammary gland, pancreas and prostate. These findings are
      leading to the development of new preclinical models for evaluating the efficacy
      of many classes of chemopreventive agents.

PMID- 9027611
TI  - Large bowel adenomas: markers of risk and endpoints.
AB  - In many large bowel chemoprevention trials adenomas have a double duty: they are
      used to identify subjects at risk for large bowel neoplasia, and also serve as
      endpoints. Many features of adenomas make them suitable for these tasks. Patients
      with adenomas are fairly numerous and easy to identify; further, the 'adenoma
      carcinoma' sequence suggests that adenomas are logical endpoints. The high
      recurrence risk among adenoma patients means that a relatively modest number of
      subjects will suffice for adequate statistical power. The are some limitations to
      the use of adenomas, however. There is clearly heterogeneity of risk for
      subsequent cancer. Patients with only small adenomas may have rates of colorectal
      cancer that are not much greater than those of the general population. Certainly
      subjects with large adenomas, and those with villous or highly dysplastic
      adenomas have a higher risk. Often, one would chose the high-risk patients for
      preventive interventions. Such a strategy makes sense from a risk-benefit point
      of view. However, from a population perspective, such a strategy may well have
      only a minor impact on the overall colorectal cancer burden. For more complete
      population-based prevention, efforts will have to be directed to the numerous
      individuals who are each at small risk, but who collectively account for most
      colorectal cancer. For this preventive approach, patients with any adenoma would
      certainly be part of the target population, and so are sensible subjects in
      chemoprevention trials. There are similar complexities in consideration of the
      use of adenomas as endpoints of chemoprevention trials. The adenomas that occur
      in prevention trials are generally small, and may not be associated with a
      greatly increased cancer risk. The issue for chemoprevention trials however, is
      not whether the endpoints are truly intermediate in the causal chain-but whether
      the intervention under study alters the adenoma recurrence risk to the same
      extent as it does for colorectal cancer risk. This is a difficult matter to
      verify, but the limited data available are encouraging. The epidemiology of
      colorectal adenomas (largely small adenomas) is similar in many regards to that
      for colorectal cancer itself. Thus to the extent that data are available, one can
      tentatively conclude that external influences affect adenomas and colorectal
      cancer similarly. To date, more than ten adenoma prevention trials have reported
      results. The data have been fairly consistent. Vitamin C (with or without vitamin
      E) has provided at most a modest protective benefit, except in one small trial in
      which it was combined with vitamin E and preformed vitamin A. beta-Carotene seems
      to be without any effect, and interventions to increase fiber and decrease fat
      intake have not indicated substantial effects. On the other hand, trials among
      familial polyposis patients have provided evidence for an impact of nonsteroidal
      anti-inflammatory drugs. Studies in progress have the potential to clarify
      greatly the preventive potential of the currently promising-but yet unproven
      chemopreventive regimens.

PMID- 9027612
TI  - The role of prostate-specific antigen in the chemoprevention of prostate cancer.
AB  - An understanding of the natural history of changes in prostate-specific antigen
      (PSA) may be valuable as a surrogate view of prostate dynamics, as a method to
      differentiate between benign and malignant growth, and as a means to assess the
      use of PSA as a tool for monitoring activity of chemoprevention agents. Although
      PSA appears to be useful as a noninvasive marker of prostatic growth, PSA changes
      should not be confused with a direct measure of tumor growth. Serum PSA levels
      are a function of tumor volume but are also influenced by the volume of benign
      epithelium, grade of carcinoma (if any), inflammation, androgen levels, growth
      factors, and the extracellular matrix. The biological functions of PSA in the
      prostate and in its secretions need to be more completely elucidated in order
      that PSA measurements may more accurately describe prostate dynamics. The
      expression of PSA is androgen-regulated. It is one of the most abundant prostate
      derived proteins in the seminal fluid. Seminogelin, a major protein in seminal
      fluid, is cleaved by PSA, and this cleavage is important in the liquefaction of
      semen. Less is known about other PSA substrates. Current PSA studies indicate
      that cancer cases exhibit an early slow linear PSA phase followed by a rapid
      exponential phase, and that PSA levels begin to increase exponentially
      approximately 7-9 years before diagnosis. The establishment of age-specific PSA
      reference ranges (ASRR) and of PSA velocity (PSAV) rates provide elements of a
      baseline from which prediction models could measure malignant potential of a
      prostatic carcinoma. Moreover, recent discoveries of different molecular forms of
      PSA in serum may allow a much more accurate differentiation of benign and
      malignant growth as well as a more potent measure of the impact of
      chemoprevention agents. If PSA doubling time is approximately 2.4-3.0 years and
      accurately reflects tumor doubling time, and if the average man has less than 0.5
      ml of latent prostatic tumor tissue and the average stage T2 cancer is
      approximately 4 ml when detected, then the available PSA data suggest that the 3
      doublings necessary to change from 0.5-4.0 ml, would take 7-12 years for a
      typical small volume tumor to reach the size of most stage T2 tumors. The
      findings that histologic cancers appear at much younger ages than previously
      known is disturbing. It indicates that disease initiation may begin sooner than
      ever thought likely. "Normal" PSA levels for younger men (< 40 years of age) may
      need to be studied, and an emphasis upon premalignant lesions in this age group
      may be necessary. Younger men may represent the most appropriate population and
      premalignant lesions the most relevant clinical factor for prostate cancer
      chemoprevention studies and trials. The molecular composition and molecular
      changes of PSA derived from premalignant lesions have yet to be elucidated, but
      such investigations may lead to a more complete understanding of the possible
      progression or transformation of normal prostate cells to premalignancy and
      subsequently to carcinoma. High grade prostatic intraepithelial neoplasia (PIN)
      in and of itself does not account for elevated serum PSA levels, but subtle
      changes in the molecular dynamics of PSA may reveal the influence of androgens
      and the impact of chemopreventive agents.

PMID- 9027613
TI  - Prostatic intraepithelial neoplasia (PIN) and other prostatic lesions as risk
      factors and surrogate endpoints for cancer chemoprevention trials.
AB  - The most efficient strategy for chemoprevention clinical trials are short-term
      studies which focus on surrogate endpoint biomarkers (SEBs) in high-risk target
      populations. High-grade prostatic intraepithelial neoplasia (PIN) is the most
      likely precursor of prostate cancer, and is found in a significant number of
      routine contemporary needle biopsies without cancer. The frequency and extent of
      PIN are decreased with androgen deprivation therapy, suggesting that it is a
      suitable endpoint biomarker for modulation. Potential SEBs for screening
      chemopreventive agents for prostate cancer in short-term Phase II trials include
      (1) histologic premalignant lesions, such as high-grade PIN; (2) biochemical
      markers, including prostate-specific antigen (PSA) serum concentration; and (3)
      morphometric markers, including nuclear texture, shape, and roundness; size and
      number of nucleoli; and number of apoptotic bodies; (4) proliferation markers,
      including MIB-1 and PCNA; (5) genetic markers, including nuclear DNA content
      (ploidy), oncogene c-erbB-2 (HER-2/neu) expression, fluorescence in situ
      hybridization for chromosome 8; and PSA-producing cells in the blood detected by
      reverse transcriptase polymerase chain reaction; and (6) differentiation markers,
      such as microvessel density as a determinant of angiogenesis. Each of these
      endpoint biomarkers is measured easily and accurately in serum or in tissue
      specimens such as formalin-fixed, paraffin-embedded needle biopsies, and may be
      modifiable by intervention. The clinical utility of these biomarkers as
      modulatable endpoints in prostate cancer chemoprevention needs to be demonstrated
      in future clinical trials.

PMID- 9027614
TI  - Molecular genetic biomarkers in hematological malignancies.
AB  - Most hematopoietic malignancies are widely disseminated even in their "early"
      stages and often do not have a well-defined localized phase. This makes them less
      amenable to conventional early screening methods such as imaging and observation.
      Furthermore, the staging systems for lymphomas are not particularly useful
      prognostically, with the possible exception of Hodgkin's disease. However, as
      currently compared with solid tumors, the extensively detailed understanding of
      the acquired (somatic) genetic lesions in leukemias and lymphomas provide useful
      molecular biomarkers for early detection. Moreover, well described high risk
      groups have been identified. These include individuals who are immunosuppressed,
      for example, iatrogenically following organ transplantation or those with AIDS.
      Also at high risk are patients treated with certain chemotherapeutic agents who
      are at risk for the development of acute non-lymphoblastic leukemia. Accordingly,
      these clinical settings might prove to be good models for evaluating molecular
      cancer risk markers and the possible introduction of chemoprevention. Here, we
      outline the biological basis for the application of biomarkers for the early
      detection of hematological neoplasia. These concepts may provide the stage for
      the creation of chemoprevention studies in leukemia and lymphoma.

PMID- 9027615
TI  - K-ras mutation in sputum of patients with or without lung cancer.
AB  - K-ras mutation appears in about 60% of patients with non-small-cell lung cancer
      (NSCLC). This frequency and its presence in normal appearing tissues point to the
      potential of ras oncogene mutation to serve as a good biomarker. Using enriched
      PCR (EPCR), which enables the detection of one mutant allele in the presence of
      10,000 normal alleles, we have determined the frequency of mutant ras alleles in
      the sputum samples of patients with or without lung cancer. Samples were
      collected from 17 patients with NSCLC and from 40 controls who suffered from non
      oncological lung diseases, including bronchitis, asthma, and pneumonia. Of the 37
      samples obtained from patients with lung cancer, 18 were found to harbor ras
      oncogene mutations (48%). Of the 40 cases that were free of lung cancer, five
      were found to harbor this mutation (12.5%). The difference between the two
      frequencies was found to be significant (P < 0.01). These findings indicate that
      (a) K-ras oncogene mutation can be identified in routinely obtained sputum
      samples of patients who may be at risk of developing lung cancer and (b) the
      higher frequency of these mutations in samples of patients with lung cancer
      points to the potential use of the ras mutation as a biomarker for either
      exogenous or endogenous exposure to carcinogens. Thus, the ability to examine
      sputum provides a powerful and convenient source of sampling and may be adapted
      for future large-scale screening.

PMID- 9027616
TI  - Clinical detection of lung cancer progression markers.
AB  - Lung cancer is the leading cause of cancer-related deaths in western countries.
      The prognosis for patients with lung cancer depends primarily on the stage of the
      tumor at the time of clinical diagnosis. New understanding of tumor biology has
      turned attention away from detection of clinical lung cancer, usually metastatic
      at presentation, toward recognition of genetic and protein markers which precede
      malignancy. Mutations of four types of genes contribute to the process of
      epithelial carcinogenesis by modifying control of cell growth. Examples of three
      of these changes have been detected in pre-malignant sputum, and validated in
      subsequent tumor. We have identified gene products (tumor associated and
      differentiation protein antigens), mutations of k-ras and p53, and microsatellite
      alterations as potential markers of subsequent malignancy. We consider the
      morphologic progression seen in archived sputum cells as the paradigm of
      neoplastic development in the lung. Although the NCl collaborative trials had
      shown that this progression is not recognized sufficiently often (sensitive) to
      be useful for lung cancer screening, this progression may be used to assess the
      timing of gene and peptide markers of carcinogenesis. Previous work has shown
      that at the time Johns Hopkins Lung Project sputum cells express moderately
      atypical metaplasia, 53% (8/15) of sputum specimens expressed common (codon 12) k
      ras or (codons 273 or 281) p53 mutations. Other investigators have reported that
      earlier morphologic changes (metaplasia) accompany 3p and 9p losses of
      heterozygosity. These observations suggest that 3p and 9p loss likely precede k
      ras or p53 mutations. Our preliminary data demonstrate that over-expression of a
      31 kD tumor associated antigen recently purified, sequenced, and identified as
      heterogeneous nuclear ribonucleoprotein (hnRNP) A2 (with cross reactivity to
      splice variant B1), is expressed in most lung cancer cases before any morphologic
      abnormality. Comparison of the accuracy of this marker with sputum cytology will
      determine its value for early lung cancer detection. Preliminary evidence
      confirms this marker greatly improves the accuracy of standard sputum cytology
      for detection of lung carcinogenesis. Clinical intervention trials must be
      undertaken to determine whether modulation of hnRNP overexpression is useful as
      an intermediate endpoint for chemoprevention.

PMID- 9027617
TI  - Examination of p53 alterations and cytokeratin expression in sputa collected from
      patients prior to histological diagnosis of squamous cell carcinoma.
AB  - Mutations in the p53 gene are detected in greater than 50% of squamous cell
      carcinomas of the lung and to a lesser extent in adenocarcinomas. The p53 protein
      is also overexpressed in a relatively high percentage of preinvasive lesions of
      the bronchial epithelium. However, unlike tumor tissue, immunoreactivity does not
      necessarily imply that cells in preinvasive lesions carry a mutant p53 allele. In
      some cases, overexpression may result from a cellular checkpoint reaction to a
      toxic or mutagenic substance such as exposure to tobacco smoke. In any case, p53
      overexpression in preinvasive lesions may serve as a biomarker for high risk
      assessment of lung cancer and other tumors in the aerodigestive tract. A study
      was designed to retrospectively analyze p53 overexpression in cells from sputum
      samples collected prior to histological tumor diagnosis. The rationale was based
      on the observation that both preinvasive and tumor cells from the bronchial
      epithelium are exfoliated into the airways and can be detected based on
      morphology in sputa. Two sets of cases were chosen: 1) patients whose first
      primary tumor was a squamous cell carcinoma containing a mutant p53 allele with
      overexpression observed in most of the tumor cells; and 2) patients whose
      squamous cell tumor did not contain a mutant p53 allele. Cells which stained
      positive for p53 expression were observed in sputum samples collected from all
      six patients whose tumors were positive for a mutant p53 allele. Also p53
      positive cells were detected on sputum slides for two of the five cases where the
      tumor DNA did not contain a mutation and/or tumor cells which overexpress p53
      were not detected in tissue sections. Although cells which stained positive for
      p53 were present in sputum from patients whose tumors contained a missense
      mutation, the presence of p53 overexpression was not specific for tumors which
      contain an altered p53 allele since overexpression was detected in sputum cells
      from patients whose tumor DNA did not contain a p53 mutation and/or tumor cells
      which stained positive for p53 were not observed in tissue sections. However, the
      p53 positive cells in sputa collected from the latter group of patients could
      have been exfoliated from other lesions which contained a mutant p53 allele. The
      accumulation of p53 in some sputum cells was concomitant with expression of
      simple epithelial type cytokeratins (CK) 8 and 18 or at least one of the other
      cytokeratins detected by a broad spectrum (PAN) CK antibody mixture. These data
      imply that most of the sputum cells which overexpress p53 are epithelial cells.
      Moreover, our results are consistent, at least in part, with other observations
      that cells which overexpress p53 in dyplasias and hyperplasias express CK 8, 18.
      We will continue to explore the possibility that expression of cytokeratins 8, 18
      and/or other cytokeratins in conjunction with p53 overexpression and/or
      morphological criteria could define a new class of atypical cells which are
      predisposed to cancer development.

PMID- 9027618
TI  - Genetic alterations as clonal markers for bladder cancer detection in urine.
AB  - Bladder cancer is the result of a clonal expansion of cancer cells in which
      multiple genetic alterations have accumulated. Point mutations of the p53 gene
      are frequently observed in bladder cancer. Loss of a retinoblastoma (Rb) allele
      is also common in bladder cancer. Recent data have shown frequent loss of
      heterozygosity (LOH) and homozygous deletion of 9p21, including the region of
      p16INK4A, a putative tumor suppressor gene, in bladder cancer. LOH is also
      observed frequently at several other chromosome regions in bladder cancer. These
      genetic changes have proved useful as clonal markers in the detection of cancer
      cells in urine. Because of their complexity, most molecular diagnostic approaches
      are not considered promising cancer screening tools in patients or high-risk
      populations. However, a new molecular approach, the examination of microsatellite
      alterations in bladder cancer and urine specimens, is a promising screening tool
      for the disease. The common genetic alterations in bladder cancer and their use
      as clonal markers in screening or diagnosis strategies will be discussed.

PMID- 9027626
TI  - Induction of psoriasiform inflammation by a bacterial superantigen in the SCID-hu
      xenogeneic transplantation model.
AB  - Psoriasis is a chronic skin disease affecting about 2% of the Caucasian
      population, characterized by co-existing inflammation and epidermal
      hyperproliferation. A T-lymphocyte-mediated autoimmune reaction induced by
      bacterial superantigens might be central in its pathogenesis. To model
      psoriasiform inflammation, we transplanted clinically uninvolved skin from
      psoriatic patients onto SCID mice. Repetitive intradermal injections with a
      bacterial superantigen and simultaneous intraperitoneal injections with the
      patients superantigen-stimulated peripheral mononuclear blood cells resulted in
      an inflammatory reaction exhibiting some of the hallmarks of psoriasis, e.g.
      epidermal hyperproliferation, papillomatosis, focal neo-expression of ICAMI, and
      an exocytotic T-lymphocytic infiltrate characterized by the expression of the
      cutaneous lymphocyte-associated antigen. These observations document the
      potential of superantigens to trigger psoriasiform dermatitis and provide a model
      to study lymphocyte homing.

PMID- 9027619
TI  - G-actin as a risk factor and modulatable endpoint for cancer chemoprevention
      trials.
AB  - Because tumorigenesis is an ongoing process, biomarkers can be used to identify
      individuals at risk for bladder cancer, and treatment of those at risk to prevent
      or slow further progression could be an effective means of cancer control given
      accurate individual risk assessment. Tumorigenesis proceeds through a series of
      defined phenotypic changes, including those in genetically altered cells destined
      to become cancer as well as in surrounding normal cells responding to the altered
      cytokine environment. A panel of biomarkers for the changes can provide a useful
      system for individual risk assessment in cancer patients and in individuals
      exposed to carcinogens. The use of such markers can increase the specificity of
      chemoprevention trials by targeting therapy to patients likely to respond, and
      thereby markedly reduce the costs of the trials. Previous studies in our
      laboratories showed the cytoskeletal proteins G- and F-actin reflect
      differentiation-related changes in cells undergoing tumorigenesis and in adjacent
      "field" cells, and a pattern of low F-actin and high G-actin is indicative of
      increased risk. Actin changes may be a common feature in genetic and epigenetic
      carcinogenic mechanisms. In a group of over 1600 workers exposed to benzidine, G
      actin correlated with exposure, establishing it as an early marker of effect. In
      another study, a profile of biomarkers was monitored in patients who underwent
      transurethral resection of bladder tumor (TURBT) and received Bacillus Calmette
      Guerin (BCG) and/or DMSO. The primary objective was to determine how the defined
      biomarkers expressed in the tumor and the field correlate with clinical response
      and recurrence. DMSO, known to modulate G-actin in vitro, was used as an agent.
      Results strongly support the hypothesis that cytosolic G-actin levels measured by
      quantitative fluorescence image analysis (QFIA) can be an important intermediate
      endpoint marker for chemoprevention and that the p300 (M344) and DNA ploidy
      markers identify a high-risk group that requires more aggressive therapy and
      recurrence monitoring. Further research with other markers has shown that DD23
      and nuclear actin, both of which identify late, specific changes, may increase
      the battery of useful markers. Taken together these studies show how biomarkers
      are employed to study individuals at risk, aid in the selection of
      chemopreventive compounds and assist in the understanding of the pathogenesis of
      malignancy.

PMID- 9027627
TI  - The inhibitory effect of UVB irradiation on the expression of p53 and Ki-67
      proteins in arsenic-induced Bowen's disease.
AB  - The aim of this study is to evaluate the effect of ultraviolet B (UVB) on arsenic
      induced Bowen's disease. Four patients were irradiated with 750 mJ/cm2 of UVB and
      biopsies were performed before treatment and 2 weeks later. Immunohistochemical
      stains of p53 and Ki-67 were compared by the labelled-streptavidin method before
      and after the UVB treatment. We found that the number of p53 and Ki-67 positive
      cells after the UVB treatment were significantly fewer than those of non-UVB
      treated specimens. These results suggest that the UVB inhibitory effect in
      Bowen's disease needs further studies to clarify its value in potentially
      retarding the progression of the hyperproliferative status in overt skin cancer
      on a molecular basis.

PMID- 9027628
TI  - Merkel cells are absent in basal cell carcinomas but frequently found in
      trichoblastomas. An immunohistochemical study.
AB  - The possibility of a neuroendocrine differentiation in basal cell carcinomas
      (BCCs) has been a matter of debate for many years. In the present
      immunohistochemical study, applying the cytokeratins 8, 18 and 20 as the most
      established markers for Merkel cells (MCs), we did not find elevated numbers of
      MCs in any of 205 BCCs. This speaks against a neuroendocrine line of
      differentiation in BCCs. In contrast, we found various amounts of MCs in 15 of 36
      trichoblastomas, which are the main benign differential diagnosis of BCC. In 4
      trichoblastomas abundant MCs were spread over the whole epithelial tumor area.
      Additionally, the trichoblastomas' overlying epidermis exhibited significantly
      much higher numbers of MCs than the uninvolved adjacent skin or the epidermis
      overlying the BCCs. These findings might be an additional aid in the distinction
      between trichoblastomas and BCCs. Furthermore, concerning the recent discussion
      about the role of MC in growth and development of follicular germ, our
      observations are another sign of regulative influences of the MC, also in
      follicular germ under pathological conditions. Trichoblastomas with high numbers
      of MCs could be characterized as showing advanced differentiation toward the
      neuroendocrine component of the hair follicle, i.e., the MCs.

PMID- 9027629
TI  - Focal necrotizing panniculitis and vascular necrosis in rats given subcutaneous
      injections of cocaine hydrochloride.
AB  - Subcutaneous injections of cocaine hydrochloride in sterile physiological saline
      were administered to rats at a dosage of 20 or 40 mg.kg-1. Resultant skin lesions
      included focal areas of alopecia (within 1 to 2 days) which progressed to
      necrosis (within 2 to 7 days). Histologically, the skin lesions were
      characterized by necrotizing panniculitis and vascular necrosis, with only small
      numbers of inflammatory cells. The lesions may be ischemic in nature, and
      associated with cytotoxic properties of cocaine.

PMID- 9027630
TI  - Histogenesis of clear cell hidradenoma: immunohistochemical study of keratin
      expression.
AB  - The expression of cytokeratins in 10 cases of clear cell hidradenoma, including 3
      cases of solid cystic hidradenoma, were examined using 21 kinds of monoclonal
      antibodies. We divided them into three histologic patterns: massive nests with a
      few lumina (M nests), nests with some tubular lumina (L nests), and nests in
      solid cystic hidradenomas (S nests). All hidradenomas showed similar
      immunoreactivities to those in the lower dermal ducts or secretory cells of
      normal eccrine glands. With antibodies against simple epithelial cytokeratins
      (CKs 7, 8, 18, and 19), however, different immunostaining was noted among the
      three histologic patterns. Namely, the M nests failed to react to them, although
      some luminal cells in the L nests revealed a positive staining. Furthermore, a
      majority of luminal cells in the S nests revealed a positive staining with them.
      Therefore, we think that the luminal cells in solid cystic hidradenoma mainly
      differentiate toward the secretory cells, and that the M nests mainly
      differentiate toward the dermal duct. Those in the L nests are thought to
      differentiate toward the dermal duct and the secretory cells. The proportion of
      the differentiation toward luminal cells of dermal ducts to the differentiation
      toward secretory cells was the main difference among the three nests. In
      addition, there was no difference in immunophenotypes between clear cells and
      epidermoid cells in the two kinds of hidradenomas.

PMID- 9027631
TI  - Detection of CD44 splice variants in formalin-fixed, paraffin-embedded specimens
      of human skin cancer.
AB  - The standard form of CD44 (CD44s) and CD44 isoforms, containing sequences encoded
      by one or several of 10 different variant CD44 exons (v1-v10), are thought to
      play a crucial role in the growth and metastasis of certain human tumors.
      Recently, monoclonal antibodies (mAbs) directed against all CD44 isoforms
      (panCD44), or against epitopes encoded by specific variant exons (CD44v) have
      been developed, which unfortunately only stain cryopreserved tissues. We wished
      to develop a technique to unmask chemically CD44s and CD44v epitopes in paraffin
      embedded specimens of human skin cancers, so that they would be accessible for
      these mAbs. To address this issue, CD44s and CD44v expression was compared in
      cryopreserved and in formalin-fixed, paraffin-embedded biopsies obtained from the
      same basal cell carcinomas (BCC), squamous cell carcinomas (SCC), primary
      malignant melanomas (PMM) and metastatic malignant melanomas (MMM). Formalin
      fixed tumors were deparaffinized and treated briefly with an antigen retrieval
      fluid (TUFTM) at 95 degrees C or left untreated. In untreated paraffin-embedded
      tissues, no CD44s or CD44v staining was detected. In contrast, in antigen
      retrieval fluid-treated biopsies CD44s and CD44v expression was identical to that
      in cryopreserved specimens of the same tumor with the exception of mAbs detecting
      v7/8 and v10. We conclude that antigen retrieval unmasks certain epitopes in
      formalin-fixed, paraffin-embedded tissues, thus facilitating future research on
      the relevance of CD44s and CD44v expression for human skin carcinogenesis.

PMID- 9027632
TI  - Primary cutaneous immunocytoma: report of an unusual case with secondary
      spreading to the gastrointestinal tract.
AB  - Cutaneous immunocytoma are low-grade B-cell lymphomas, which affect the skin
      either primarily or secondarily. Primary cutaneous immunocytomas usually present
      with one or a small number of lesions, mainly in the extremities. They generally
      remain confined to the skin. Histologically, there are polymorphous infiltrates
      of cells, in which the presence of monoclonal plasma cells is characteristic. We
      describe a case of cutaneous immunocytoma with secondary spread to the
      gastrointestinal tract.

PMID- 9027633
TI  - Detection of human papillomavirus DNA in squamous cell carcinomas of a patient
      with mycosis fungoides: report of a case.
AB  - Human papillomaviruses (HPV) have been associated with squamous cell carcinomas
      (SCC) of the skin in both the immunocompetent and the immunocompromised
      individual. A paucity of literature, however, exists concerning the presence of
      HPV in SCCs from patients with mycosis fungoides (MF)-[cutaneous T-cell lymphoma
      (CTCL.)]. We describe a case of multiple SCCs in which HPV DNA was detected over
      a 9-year period from a patient with MF. This patient with a long history of MF
      developed 7 small red scaly indurated lesions of sun and non-sun-exposed areas
      during a 9-year period (1981-1989). Histologic examination of all the lesions
      revealed that they were SCCs. The patient had no recorded history of arsenic
      exposure. To investigate the possible role of HPV as a co-carcinogen, we tested
      the 7 cases of SCC for HPV. Polymerase chain reaction (PCR) was performed on
      formalin-fixed tissue sections using HPV L.1 consensus sequence primers. Four of
      the 7 SCCs were positive for HPV DNA. These results suggest a possible role for
      HPV as a co-carcinogen in the development of SCCs in this patient.

PMID- 9027634
TI  - Oral pseudolymphoma: a report of two cases.
AB  - Although 2% to 10% of lymphomas present first in the oral cavity and lymphomas
      are the third most common oral malignancy, pseudolymphoma is a very infrequent
      problem within oral pathology. Two cases of oral pseudolymphoma are presented.
      Both were old persons with an infiltrative lesion on the oral mucosa that
      histologically showed a dense polymorphous infiltrate with some nuclear atypia
      that raised the problem of lymphoma versus pseudolymphoma. Both lesions
      disappeared with no relapse after 2-years' follow-up. Histologically, case 1 was
      mainly a lymphohistiocytic infiltrate whose histiocytic component showed nuclear
      features that mimicked Hodgkin's cells. In case 2, the infiltrate was mainly
      composed of histiocytes and eosinophils. The suspicion of malignancy here was a
      consequence of a high mitotic rate of histiocytes and of the large hyperchromatic
      nuclei of the intraepithelial lymphocytes. Similarities and differences with
      other pseudomalignant (lymphomatoid papulosis and atypical histiocytic granuloma)
      and inflammatory (traumatic ulcerative granuloma with stromal eosinophilia)
      disorders, as well as with some histiocytoses, are discussed. In the absence of a
      wider experience on this subject, an objective description of new cases seems
      appropriate.

PMID- 9027635
TI  - Superinfected cutaneous angiosarcoma: a highly malignant neoplasm simulating an
      inflammatory process.
AB  - This report describes a patient with a poorly differentiated cutaneous
      angiosarcoma (CA) of the face superinfected with pseudomonas aeruginosa.
      Neoplastic cells were positive for CD-34, CD-31 and vimentin, whereas they failed
      to express other vascular markers such as Factor VIII and Ulex europeaus lectin.
      The tumor spread rapidly through the skin and the superficial soft tissue before
      metastasizing. The patient died of disease 6 months after histopathological
      diagnosis. An autopsy revealed widespread metastases in the lung and the liver.
      The aim of this report is to call attention to some circumstances in which CA may
      masquerade as an inflammatory process, delaying the right diagnosis with serious
      consequences for the patient.

PMID- 9027636
TI  - Milia en plaque associated with pseudoxanthoma elasticum.
AB  - We report a woman with numerous milia occurring in a plaque-type distribution in
      the postauricular area, who has suffered from cutaneous pseudoxanthoma elasticum
      on both sides of the neck. Milia may arise primarily or may follow a number of
      dermatoses. We believe this is a unique case because milia en plaque coexisting
      with pseudoxanthoma elasticum does not appear to have been reported previously.

PMID- 9027637
TI  - Effect of omeprazole on the course of associated esophagitis and laryngitis.
AB  - Esophagitis has increasingly been implicated as a cause of chronic laryngitis and
      there is some evidence that gastro-esophageal reflux disease (GERD) is more
      common in patients with laryngitis. The aim of this study was to evaluate whether
      patients with esophagitis and laryngitis responded to treatment with omeprazole.
      Of 74 consecutive patients with endoscopically proven GERD, 21 had laryngitis.
      These 21 patients with associated esophagitis and chronic laryngitis were treated
      for 4 weeks with omeprazole 40 mg per day. After 2 weeks of treatment and at the
      conclusion of the study, 2 weeks later, esophagoscopy and laryngoscopy were
      performed and the patients responded to a questionnaire on their symptoms. The
      follow-up period was 1 year. Twenty-one of the 74 patients (28.4%) had
      esophagitis (grade I, n = 12; grade II, n = 9) and associated laryngitis (grade
      I, n = 14; grade II, n = 7). The severity of the esophagitis accorded with the
      severity of the laryngitis. After 2 weeks' treatment with omeprazole, both the
      esophageal and the laryngeal symptoms had improved in all 21 patients.
      Endoscopically, the healing rates were 62% for esophagitis and 33.3% for
      laryngitis. At the end of the study period, at 4 weeks, all patients were symptom
      free and the esophagitis and laryngitis had healed completely. No patient
      suffered from drug-induced side effects. Patients with associated laryngitis and
      esophagitis should be given adequate anti-reflux therapy. Both the laryngeal and
      esophageal symptoms improved with the omeprazole treatment, suggesting that
      reflux was the underlying etiology.

PMID- 9027638
TI  - Effect of cysteamine on gastric nerve fibers containing gastrin-releasing peptide
      in the rat.
AB  - In rats, changes in gastric nerve fibers containing gastrin-releasing peptide
      (GRP) in cysteamine-induced duodenal ulcer were investigated in relation to the
      dynamics of gastrin-producing cells (G-cells). Marked increases in gastric acid
      secretion and serum gastrin level were observed from 2 h after the administration
      of cysteamine. The number of G-cells was significantly decreased from 2 h after
      the injection of cysteamine. Two and 4 h after the administration of cysteamine,
      the G-cells showed ultrastructural changes characterized by a markedly decreased
      number of secretory granules. Circulating GRP levels were significantly elevated
      from 2 h after the administration of cysteamine. In the control group given
      vehicle only, nerve fibers showing immunoreaction for GRP formed a fine network
      in the gastric wall and were densely distributed in the oxyntic mucosa, located
      close to capillaries and demonstrated varicosities that contained either small
      clear vesicles or GRP-immunopositive vesicles with large cores. Eight h after the
      administration of cysteamine, there was depleted GRP immunoreactivity, evidenced
      by a markedly decreased number of vesicles, with large electron-dense cores, in
      the oxyntic mucosa. These findings suggest that, in cysteamine-induced duodenal
      ulcer, alterations in gastric nerve fibers containing GRP may be related to
      hypergastrinemia.

PMID- 9027639
TI  - Evaluation of omental implantation for perforated gastric ulcer therapy: findings
      in a rat model.
AB  - Omental implantation, a surgical procedure in which a perforated gastric or
      duodenal ulcer is repaired by drawing and implanting a portion of the omentum
      into the digestive tract, accelerates ulcer healing and inhibits ulcer
      recurrence. However, the mechanisms underlying these beneficial effects are
      largely unknown. To clarify these mechanisms, we investigated ulcer healing in
      two groups of rats in which acetic acid-induced gastric ulcers were perforated.
      Omental implantation was used for repair in one group and simple suturing was
      employed in the other group. Greater anti-inflammatory and angiogenic activity
      and accelerated collagen synthesis were seen in the omental implantation group.
      Basic fibroblast growth factor (bFGF)-mediated angiogenesis was noted in this
      group, as well as transforming growth factor-beta 1 (TGF-beta 1) activity within
      and around the omentum, resulting in abundant collagen production. It was
      confirmed that omental implantation accelerated ulcer healing and inhibited ulcer
      recurrence, and the presence of bFGF and TGF-beta 1 played a significant role in
      both these phenomena.

PMID- 9027640
TI  - Therapeutic effect of egualen sodium (KT1-32), a new antiulcer agent, on chronic
      gastritis induced by sodium taurocholate in rats.
AB  - We investigated the therapeutic effects of egualen sodium (KT1-32), a new
      antiulcer agent, on chronic erosive and atrophic gastritis induced by 5 months'
      administration of sodium taurocholate (TCA; 5 mM) in rats. The chronic gastritis
      was manifested by mucosal surface injuries (erosions), reduced mucosal thickness,
      reduction of the number of parietal cells, infiltration of inflammatory cells,
      and proliferation of collagenous fiber. Egualen sodium, (10-100 mg/kg, t.i.d.)
      administered orally to the rats for 2 weeks after the withdrawal of TCA, dose
      dependently and significantly decreased the total length of erosions. The
      indicators of atrophic gastritis, i.e., reduced mucosal thickness and reduction
      in the number of parietal cells, were improved dose-dependently by the
      administration of this agent. Egualen sodium also reduced the inflammatory cell
      infiltration and the proliferation of collagenous fiber in the gastric mucosa in
      a dose-dependent manner. The reduced staining of neutral gastric mucus was
      improved by a high dose (100 mg/kg) of egualen sodium. The therapeutic effects of
      egualen sodium on experimental gastritis were superior to those of sofalcone and
      sodium guaiazulene 3-sulfonate. These results suggest that egualen sodium may be
      a promising agent for the treatment of erosive and atrophic gastritis.

PMID- 9027641
TI  - Quantitative analysis of numerical chromosome aberrations in various
      morphological types of colorectal carcinomas.
AB  - Quantitative analysis by fluorescence in situ hybridization (FISH) on thin
      paraffin-embedded tissue sections, using specific probes for chromosomes 11, 17,
      and 18 was employed in various morphological types of early and advanced
      colorectal cancer to clarify tumor cytogenetics. The chromosome index (CI) was
      calculated as a quantitative measure of the chromosome copy number. Compared with
      the CI of normal epithelium, the CI of chromosome 11 in villous components of
      adenomas or polypoid early cancers was decreased, while the CI in flat type or
      advanced colorectal cancers, conversely, was increased (P < 0.05). The CI of
      chromosome 17 in villous components of adenomas and all cancers was higher than
      that of normal epithelium (P < 0.05), but the differences were not significant.
      In protruding advanced cancers, the CI of chromosome 18 was significantly
      decreased (P < 0.01) compared to the CI of normal epithelium. There was no
      significant chromosomal heterogeneity between the superficial and the deepest
      layer in each cancer. In mucosa adjacent to sessile and flat type cancers, the CI
      of chromosome 17 was significantly higher than the CI in normal epithelium or
      adenomas (P < 0.05). These results suggest that numerical chromosome aberrations
      are associated with the histological type of adenoma and the morphological
      diversity of cancer in the colorectum, and that chromosome 17 abnormality occurs
      in mucosa adjacent to sessile and flat cancers.

PMID- 9027642
TI  - Hepatitis C virus subtype 3b infection in a hospital in Japan: epidemiological
      study.
AB  - To elucidate the epidemiology of infection with hepatitis C virus (HCV) subtype
      3b (a rare subtype thought to have originated in Southeast Asia) in Japan, we
      examined the genotypic subtype in 1397 patients with HCV-related chronic liver
      diseases. Of 1330 patients with identified HCV RNA genotypes. 960 had subtype 1b,
      243 had subtype 2a, 97 had subtype 2b, 14 (1.1%) had subtype 3b, and 16 had other
      types of HCV or mixed subtypes. The age, gender, and severity of liver disease in
      patients with HCV subtype 3b did not differ from these features in patients with
      other subtypes. Eleven of the 14 patients with the 3b subtype had once worked at
      Company A in Tokyo, Japan. Multivariate logistic analysis showed that working
      history at that company was independently associated with the incidence of the
      subtype; the risk ratio was 207.2 (P < 0.0001). All 11 patients from Company A
      had received medical services, between 1953 and 1981, at Clinic C, which
      undertook medical care of the company staff. All 11 patients had received
      repeated intramuscular or intravenous injections for treatment of various
      diseases or for preventive vaccination for contagious diseases. The rare HCV
      subtype 3b, appeared to have been transmitted among the employees of a company
      through the performance of certain medical practices.

PMID- 9027643
TI  - Expression of interferon-alpha receptor mRNA in the liver in chronic liver
      diseases associated with hepatitis C virus: relation to effectiveness of
      interferon therapy.
AB  - To investigate whether interferon-alpha receptor (IFN-alpha Rc) expression was
      related to the effectiveness of interferon therapy in hepatitis C virus (HCV)
      associated chronic liver disease (CLD). IFN-alpha Rc mRNA was investigated by
      reverse transcription polymerase chain reaction (RT-PCR) in liver biopsies and
      peripheral blood mononuclear cells (PBMCs) from 40 patients with HCV-associated
      CLD who subsequently received IFN-alpha therapy. IFN-alpha Rc mRNA in the liver
      was detected in 18 of 20 (90%) responders to IFN and in 5 of 20 (25%) non
      responders (P < 0.01). In PBMCs, IFN-alpha Rc mRNA was detected in all patients
      regardless of response to IFN. Increased histological hepatitis activity and
      liver fibrosis were significantly related to the absence of IFN-alpha Rc mRNA.
      The HCV-RNA genotype showed no significant relationship to IFN-alpha Rc mRNA
      expression. Our results suggest that IFN-alpha Rc mRNA expression in the liver,
      but not in PBMCs, is closely associated with the effectiveness of IFN-alpha
      therapy in HCV-associated CLD.

PMID- 9027644
TI  - Analysis of serum hepatitis A virus antibody response in different courses of
      hepatitis A virus infection.
AB  - Changes in the serum hepatitis A virus antibody (anti-HAV) response in patients
      with different clinical courses of HAV infection were examined using immune
      adherence hemagglutination (IAHA). Anti-HAV was detected 2-6 weeks after the
      onset of clinical symptoms in patients with the typical course of acute hepatitis
      A and 1-4 weeks after the onset in those with fulminant hepatitis A. Maximal anti
      HAV titers were observed 8-20 weeks after the onset of clinical symptoms, and
      changes in anti-HAV were similar in the typical and the prolonged course of acute
      hepatitis A, but maximal antibody titers were higher in the prolonged course.
      Maximal anti-HAV titers in patients with subclinical HAV infection were
      significantly lower than titers in patients with the typical and prolonged
      courses of acute hepatitis A, and in those with fulminant hepatitis A. High
      titers of anti-HAV remained positive for at least 6 years after infection in
      patients with clinical infection and for at least 4 years in patients with
      subclinical infection on follow-up. These findings suggest that the maximum anti
      HAV titer correlates with the clinical severity of HAV infection; knowledge of
      the antibody response should be useful for analyzing the pathogenesis of HAV
      infection.

PMID- 9027645
TI  - Consecutive evaluation of immunoglobulin M and G antibodies against hepatitis E
      virus.
AB  - Hepatitis E virus (HEV) infection is sporadic in the Guangzhou city southern
      China. However, the evaluation of antibodies to HEV during consecutive time
      periods after infection has not been reported. We utilized enzyme immunosorbent
      assay (ELISA) to defect IgM and IgG anti-HEV in consecutive serum specimens from
      patients with acute hepatitis E and compared that data with detection rates of
      IgM and IgG anti-HAV in patients with acute hepatitis A. IgM anti-HEV can be
      detected as early as 4 days after onset of disease symptoms in some patients. The
      detection rate of IgM anti-HEV is significantly higher in specimens collected
      within 4 weeks (95%) of onset than in those specimens collected 4 to 18 weeks
      after onset (67.6%) (P < 0.005). IgM anti-HEV had a similar pattern to IgM anti
      HAV and can be used as a marker of acute HEV infection. In contrast with IgG anti
      HAV, 56.8% of the specimens did not contain detectable levels of IgG anti-HEV (P
      < 0.005). One should be cautioned against making a diagnosis of HEV infection
      solely by the currently available assays for IgG anti-HEV. In conclusion, IgM
      anti-HEV can be used as a reliable and sensitive marker for recent HEV infection,
      but serum specimens should be collected within 4 weeks after onset of symptoms to
      avoid false-negative results. In contrast, we should be aware of the failure to
      develop IgG anti-HEV in some patients. These patients carry the risk of
      reinfection.

PMID- 9027646
TI  - Serum and bile lipid levels in patients with and without gallstones.
AB  - The aim of the present study was to investigate predisposing factors that lead to
      the formation of gallstones. In a group of 70 patients (51 with gallstones and 19
      without, 20 possible risk factors were studied: percent of ideal body weight, the
      presence of superoxide dismutase in erythrocytes and in serum, lipid peroxide in
      serum, total serum cholesterol (Ch), high-density lipoprotein (HDL)-cholesterol
      (Ch), low-density lipoprotein (LDL)-Ch, very low-density lipoprotein (VLDL)-Ch,
      serum triglyceride (TG), HDL-TG, LDL-TG, VLDL-TG, serum bile acids (lithocholic
      acid, deoxycholic acid, chenodeoxy cholic acid, ursodeoxy-cholic acid, and cholic
      acid) and serum apolipoproteins (apo A-1, apo B-100, and apo A-1/apo B-100).
      Levels of apo B-100 and serum insulin in patients with gallstones were strikingly
      higher, and superoxide dismutase in erythrocytes was significantly lower than in
      individuals with no gallstones. Apo A-1 and HDL-Ch were also higher and LDL-Ch
      was lower in the gallstone group, albeit non-significantly so (P > 0.05) by t
      test. However, Apo A-1, HDL-Ch, and LDL-Ch showed remarkably good discriminatory
      power in stepwise discriminant analysis of the 20 factors. Bile lipid composition
      was also measured and the cholesterol saturation index was calculated, but no
      significant differences were seen between the two groups. The results demonstrate
      that serum lipid patterns differ to some extent in patients with and without
      gallstones. Lipid derangement may contribute to the development of gallstone
      disease.

PMID- 9027647
TI  - Deconjugation of bilirubin accelerates coprecipitation of cholesterol, fatty
      acids, and mucin in human bile--in vitro study.
AB  - To examine the initial step of brown pigment gallstone formation, sterile human
      gallbladder bile samples were incubated with or without beta-glucuronidase in
      vitro. Enhanced bilirubin deconjugation achieved by adding beta-glucuronidase
      significantly accelerated the formation of a precipitate that contained bilirubin
      (28.2 +/- 3.8% of dry weight), cholesterol (14.3 +/- 5.2%), free fatty acids
      (12.0 +/- 1.3%), and glycoprotein (10.0 +/- 6.7%). Both the composition and
      scanning electron microscopic appearance of the precipitate were similar to these
      features in brown pigment gallstones. The cholesterol saturation index and
      nucleation time in the supernatant did not change with various incubation
      periods. The weight ratios of bilirubin to cholesterol in the precipitates
      correlated with those in bile (r = 0.76; P = 0.017). Gel chromatography of the
      precipitate showed high molecular weight glycoprotein to be the major
      constituent. Bilirubin, cholesterol, fatty acids, and mucin were found to
      coprecipitate in accordance with bilirubin deconjugation, which process may play
      an important role in an early stage of the formation of brown pigment gallstones.

PMID- 9027648
TI  - Bacterial adhesion on hydrophilic heparinized catheters, with compared with
      adhesion on silicone catheters, in patients with malignant obstructive jaundice.
AB  - To study the inhibitory effects on bacterial adhesion of a newly devised,
      hydrophilic heparinized catheter to be used in patients with malignant
      obstructive jaundice, a randomized controlled study of indwelling endoprostheses
      was performed, using implantable port-connected heparinized catheters (n = 25)
      and silicone catheters (n = 21). Catheters withdrawn from patients were cultured
      for bacteria and examined by electron microscopy for the presence of adherent
      organisms. In vitro examination of the two type of catheters exposed to
      suspensions of Eschericia coli and Staphylococcus aureus was performed using
      electron microscopy and a luminometer. The formation of a biofilm coated with
      glycocalyces was found in silicone catheters, but not in the heparinized
      catheters. In vitro experiments demonstrated little bacterial adhesion to the
      heparinized surface, but significant formation of biofilm on the silicone
      surface. Anionically charged heparinized catheters have inhibitory effects on
      bacterial adhesion, and the surface charge of the catheter may be a factor in
      inhibiting this adhesion.

PMID- 9027649
TI  - Giant epiphrenic diverticulum with achalasia occurring 20 years after Heller's
      operation.
AB  - We report a case of giant epiphrenic diverticulum in a 43-year-old woman who
      underwent Heller's myotomy because of achalasia 20 years earlier. She complained
      of heartburn and dysphagia from March of 1991 and was hospitalized in our
      institution. An upper gastrointestinal X-ray examination with contrast medium
      revealed a large hemispheric lesion (7.8 x 4.8 cm) occupying the right posterior
      wall of the lower thoracic and abdominal esophagus. Manometry revealed a motility
      disorder and high pressure of the lower esophageal sphincter due to achalasia.
      Therefore she was diagnosed as having a giant diverticulum with achalasia after
      Heller's operation. She underwent transhiatal esophagectomy and reconstruction
      with placement of a gastric tube on June 4, 1992. Pathology results on the
      resected specimen revealed a false diverticulum. She has been doing well for 4
      years since the operation. It has been said that a complication of incomplete
      long myotomy causes pulsion diverticulum, but we could not find a case of
      epiphrenic diverticulum after myotomy for achalasia reported in the literature in
      the last 10 years.

PMID- 9027650
TI  - Infective dyspepsia in a heart transplant recipient.
AB  - We report the coexistence of symptomatic viral, bacterial, and fungal infection
      of the upper gastrointestinal tract in a heart transplant recipient. Endoscopic
      findings were normal at all levels but, because of severe symptoms and recent
      conversion to positive serology for Cytomegalovirus, biopsies were taken. These
      showed esophageal candidiasis and gastric Helicobacter infection that has
      hitherto been unreported in cardiac transplant recipients.

PMID- 9027651
TI  - Double cancer of the stomach, one AFP-producing tumor.
AB  - In recent years, many cases of alpha-fetoprotein-producing gastric cancer (AFPGC)
      characterized by increased serum levels of alpha-fetoprotein (AFP) and AFP
      positivity of the gastric cancer have been reported. Here we present a case of
      AFPGC coexistent with a different histological type of gastric cancer: The AFPGC
      was Borrmann type 1 advanced gastric cancer with multiple liver metastasis and
      appeared to produce both AFP and des-gamma-carboxy prothrombin (PIVKA-II). The
      second cancer was IIc type early gastric cancer and did not produce AFP. Despite
      receiving palliative chemotherapy, the patient died, due to hepatic failure, 45
      days after admission.

PMID- 9027652
TI  - Effects of erythromycin in chronic idiopathic intestinal pseudo-obstruction.
AB  - The prokinetic effects of erythromycin, a macrolide antibiotic, on the
      gastrointestinal tract as a motilin receptor agonist and its potential value for
      the treatment of gastrointestinal motility disorders have recently attracted
      interest. The effects of erythromycin on the clinical symptoms and
      gastrointestinal motility of patients with chronic idiopathic pseudo-obstruction
      have not been investigated extensively. We presented a case of chronic idiopathic
      intestinal pseudo-obstruction, in a 67-year-old man in whom oral erythromycin
      (900 mg/day) dramatically improved postprandial abdominal distention, nausea, and
      vomiting. Other agents with prokinetic effects on intestinal motility, i.e.,
      cisapride, domperidone, metoclopramide, and trimebutine maleate did not have a
      favorable effect. Gastric emptying, measured by the sulfamethizole method; and
      intestinal transit, evaluated using radio-opaque markers, were markedly improved
      by treatment with erythromycin. Our experience suggests that the prokinetic
      effects of erythromycin may be of therapeutic value in chronic idiopathic
      intestinal pseudo-obstruction.

PMID- 9027653
TI  - Ulcerative colitis with overexpression of p53 preceding overt histological
      abnormalities of the epithelium.
AB  - A 53-year-old man with a 22-year history of ulcerative colitis(UC) (pancolitis),
      had an ulcerating rectal tumor. Resection of the rectum and sigmoid colon was
      performed. Pathology showed an expansive ulcerating adenocarcinoma tumor (type 2)
      invading the adventitia against a background of UC in a resolving phase.
      Dysplasia was also found in granular and flat mucosa adjacent to the invading
      carcinoma. Immunostaining for p53 showed diffuse positivity in both the carcinoma
      and dysplasia, and also in the mucosa with indefinite dysplasia or no dysplasia
      neighboring the dysplasia and carcinoma. Mapping of neoplasms and the area with
      p53 protein overexpression showed that the grade of dysplasia increased as the
      lesion approached the invasive carcinoma and that the mucosa with dysplasia was
      surrounded by mucosa without dysplasia or indefinite for dysplasia, but with p53
      protein overexpression. In some areas without dysplasia showing p53
      overexpression, there was significant morphometric enlargement of the area and
      diameter of the nucleus p53 Immunostaining is a good marker for assessing the
      genetic alterations that precede histological abnormalities and for diagnosing
      carcinoma in UC. Objective findings such as p53-protein overexpression and
      morphometric values should be used to evaluate cytological abnormalities in UC,
      as well as in common colorectal cancer.

PMID- 9027654
TI  - Cystic mesothelioma of the peritoneum.
AB  - We report a case of cystic mesothelioma of the peritoneum (CMP), a rare tumor.
      The magnetic resonance imaging (MRI) findings and the histochemical features were
      studied. The patient was an 18-year-old women who presented with upper abdominal
      pain. Abdominal ultrasonography and computed tomography showed a well defined
      cystic mass with a solid papillary projection in its lumen. MRI of the cyst
      showed high intensity on T2- and proton weighted images and low intensity on T1
      weighted images, and the solid projection showed low intensity on T2- and proton
      weighted images and slight low intensity on T1-weighted images, on which it was
      well enhanced. The lesion was suspected to be a benign cyst, such as a
      hemangioma, lymphangioma, or a splenic or pancreatic cyst. Complete surgical
      resection was performed. The resected specimen consisted of a unilocular cystic
      mass, with a solid projection, weighing 260 g and measuring 10 cm in diameter.
      The final diagnosis, arrived at by histopathological examination, was low-grade
      malignant CMP. The tumor cells were strongly positive for keratin, weakly
      positive for vimentin, and negative for epithelial membranous antigen. The
      patient is now well and symptom-free with no recurrence 19 months after
      operation. CMP is a rare tumor; only 12 cases have previously been reported in
      Japan.

PMID- 9027655
TI  - Diffuse cavernous hemangioma of the rectum: MR imaging with endorectal surface
      coil and sphincter-saving surgery.
AB  - We describe the clinical features, diagnostic procedures, and treatment of two
      patients with diffuse cavernous hemangioma of the rectum. Sphincter-saving
      operations were performed in both patients, with satisfactory results. Magnetic
      resonance imaging (MRI) with an endorectal surface coil, as well as a
      conventional body coil, was used to determine the extent of the hemangiomas. We
      recommend sphincter-saving surgery for the treatment of this benign disease that
      can cause life-threatening hemorrhage. MRI with an endorectal coil achieves
      higher-resolution images than conventional MRI.

PMID- 9027656
TI  - Subcapsular hematoma of the liver and pylethrombosis in the setting of
      cholestatic liver injury.
AB  - We describe a subcapsular hematoma of the liver and pylethrombosis in a patient
      who developed cholestasis 4 days after severe burn injury. On the 44th hospital
      day, severe anemia suddenly appeared with no determinable cause. This was the
      initial manifestation of hepatic hematoma. Cholestatic liver injury of unknown
      cause lasted throughout the clinical course. The patient subsequently died of
      hepatic failure 27 months after the burn injury. An autopsy confirmed
      pylephlebitis and pylethrombosis, which were considered to have contributed to
      the hepatic failure. This was a rare case of hepatic hematoma and pylephlebitis
      and pylethrombosis that developed after burn injury.

PMID- 9027657
TI  - A long-surviving patient with recurrences of hepatic alveolar echinococcosis
      after traumatic intra-abdominal rupture.
AB  - Alveolar echinococcosis of the liver (AEL) takes a progressive and malignant
      course. Intra-abdominal dissemination of the parasite has a miserable outcome.
      Complete resection of the lesion is indispensable for the curative treatment of
      AEL. We experienced an extremely rare case of intra-abdominal rupture of AEL. The
      patient had repeated recurrences of AEL following the traumatic rupture of the
      lesion. After repeated resections of the lesions and appropriate medication, the
      patient is still alive more than 25 years since the initial onset of the disease.
      AEL differs from unilocular echinococcosis in terms of biological behavior. We
      compare the pathophysiology of the two conditions.

PMID- 9027658
TI  - Intraductal papillary adenocarcinoma with mucin hypersecretion and coexistent
      invasive ductal carcinoma of the pancreas with apparent topographic separation.
AB  - We report a 66-year-old man who had a cystic intraductal papillary adenocarcinoma
      containing a papillary adenoma, in the head of the pancreas and a coexistent
      invasive, well differentiated solid tubular adenocarcinoma in the tail of the
      pancreas. He was hospitalized with acute epigastralgia. Computed tomography
      demonstrated a multilocular cystic mass in the head of the pancreas and a solid
      tumor in the tail. Endoscopic retrograde pancreatography showed mucin secretion
      from an enlarged papilla of Vater, marked dilatation of the main pancreatic duct
      in the head and body, cystic dilatation of the uncinate branch, and irregular
      narrowing of the main pancreatic duct in the tail. Total pancreatectomy was
      performed. Between the cystic tumor and the solid tumor there was a distance of
      4.8 cm of normal pancreatic parenchyma and duct, recognized both grossly and
      microscopically. The patient died 35 months after the operation. At autopsy,
      peritonitis carcinomatosa was found in the abdominal cavity. Microscopically,
      disseminated nodules were also well differentiated tubular adenocarcinoma. The
      apparent anatomic separation of these two tumors within the pancreas is extremely
      unusual.

PMID- 9027659
TI  - Semi-quantitative analysis of telomerase in pancreatic ductal adenocarcinoma.
AB  - Using a polymerase chain reaction-based amplification assay, we measured
      telomerase activity in surgically resected pancreatic ductal carcinomas (n = 16
      cases) and normal ducts (n = 6), comparing findings with the telomerase activity
      of a human pancreatic cancer cell line, MIA PaCa-2, as a standard, i.e., relative
      telomerase activity was determined. Telomerase activity was expressed as the
      equivalent telomerase intensity of the number of cells of MIA PaCa-2 per
      microgram protein of tissue samples. The median value for telomerase activity in
      normal pancreatic ducts was 0.13 and the 25th and 75th percentile were 0.01 and
      0.76. The median value for telomerase activity in pancreatic ductal
      adenocarcinoma was 34.7 (25th percentile, 4.98; and 75th percentile, 296),
      significantly higher than that of normal ducts (P < 0.001). When the cut-off
      value was set at 1.0 and 3.0, the telomerase positivity rate of pancreatic ductal
      adenocarcinomas was 100% and 81.3%, respectively. Telomerase may be specific
      marker for pancreatic ductal carcinomas.

PMID- 9027660
TI  - Cyclooxygenase, NSAIDs, and colorectal cancer.
AB  - Prevention of human diseases has become a major focus of biomedical investigators
      around the world. Our current screening and treatment regimens for colorectal
      cancer are not effective, as indicated by the fact that this disease is the
      second leading cause of death from cancer in the United States. Recently
      published reports indicate that continuous use of aspirin reduces the relative
      risk of colorectal cancer by about 50%. Other work demonstrates that NSAIDs cause
      regression of adenomas in patients with familial adenomatous polyposis and
      prevent the development of colon tumors in carcinogen-treated animals. This
      review is a summary of the literature and includes an analysis of recent reports
      indicating the potential molecular basis for the chemoprotective effects of
      NSAIDs.

PMID- 9027662
TI  - Urinary 1 beta-hydroxyursodeoxycholic acid during ursodeoxycholic acid therapy.

PMID- 9027661
TI  - Alterations of the mucosal immune system in inflammatory bowel disease.
AB  - The normal intestinal immune system is under a balance in which proinflammatory
      and anti-inflammatory cells and molecules are carefully regulated to promote a
      normal host mucosal defense capability without destruction of intestinal tissue.
      Once this careful regulatory balance is disturbed, nonspecific stimulation and
      activation can lead to increased amounts of potent destructive immunologica and
      inflammatory molecules being produced and released. The concept of balance and
      regulation of normal mucosal immune and inflammatory events is indicative of how
      close the intestine is to developing severe inflammation. The normal intestinal
      mucosal immune system is constantly stimulated by lumenal contents and bacteria.
      The stimulatory molecules present in the intestinal lumen that activate and
      induce subsequent mucosal immunologic and inflammatory events include bacterial
      cell wall products, such as peptidoglycans and lipopolysaccharides, as well as
      other chemotactic and toxic bacterial products that are produced by the many
      different types of bacteria within the gastrointestinal tract. These highly
      stimulatory bacterial cell wall products are capable of activating macrophages
      and T lymphocytes to release potent proinflammatory cytokines, including
      interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF
      alpha). IL-1, IL-6, and TNF-alpha increase the presence of human leukocyte
      antigen (HLA) class II antigen-presenting molecules on the surfaces of epithelial
      cells, endothelial cells, macrophages, and B cells, thus increasing their ability
      to present lumenal antigens and bacterial products. The proinflammatory cytokines
      IL-1 and TNF-alpha also increase the ability of epithelial cells, endothelial
      cells, macrophages, and fibroblasts to secrete potent chemotactic cytokines, such
      as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), which
      serve to increase the movement of macrophages and granulocytes from the
      circulation into the inflamed mucosa. Thus, through lumenal exposure to potent,
      nonspecific stimulatory bacterial products, the state of activation of the
      intestinal immune system and mucosal inflammatory pathways are markedly up
      regulated. This raises the question of whether there is a deficiency in effective
      down-regulation through the absence of normally suppressive cytokines such as
      interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), interleukin-4
      (IL-4), and IL-1 receptor antagonist. Normally, the turning off of the active and
      destructive immunologic and inflammatory events should occur following the
      resolution of a bacterial or viral infection that has been appropriately defended
      against and controlled by the mucosal immune system. In inflammatory bowel
      disease (IBD), however, the down-regulatory events and processes that should turn
      off the immunologic and inflammatory protective processes, once the pathogenic
      agent has been cleared, appear to be deficient or only partially effective. We
      may find that we ultimately are dealing with disease processes that have more
      than one genetic or cellular basis. The improved understanding of the
      immunopathophysiology of IBD will allow exploration of novel immunologic and
      genetic approaches, such as gene replacement therapy, administration of a
      suppressor cytokine or an altered cell surface antigen, the administration of
      humanized monoclonal antibodies directed against proinflammatory cytokines, or
      the development of newer strategies against fundamental cell biologic mechanisms
      such as adhesion molecules.

PMID- 9027667
TI  - Sensitivity to antibacterials of Staphylococcus aureus isolated from different
      types of skin infections.
AB  - We examined the antibacterial susceptibility of Staphylococcus aureus isolated
      from several types of skin infections, which were classified into four groups:
      (i) impetigo, (ii) folliculitis, (iii) atopic dermatitis and eczema and (iv)
      ulcers and decubitus. The 50% minimal inhibitory concentration (MIC50) of the
      antibacterial agents was 3.13 micrograms/ml or lower, except that of gentamicin
      with isolates from the impetigo groups (25 micrograms/ml). The MIC90 of
      gentamicin was 50 micrograms/ml or more for isolates from all four groups. The
      isolates from the ulcers and decubitus group showed multiple resistance against
      antibacterial agents. The frequency of methicillin-resistant S. aureus was low,
      but was highest, at 25%, in the isolates from the ulcers and decubitus group. Few
      isolates from the atopic dermatitis and eczema group were resistant, and there
      was little difference in antibacterial resistance between isolates from atopic
      dermatitis and eczema.

PMID- 9027668
TI  - Sensitivity to antibacterials of Staphylococcus aureus isolated from skin
      infections: a comparison of two hospitals.
AB  - We compared the sensitivities to antibacterials of Staphylococcus aureus strains
      isolated from skin infections in two hospitals of different sizes. There were
      differences between the two hospitals in the proportions of the strains isolated
      that were resistant to certain drugs, and these differences may be related to the
      patterns of drug use at each hospital. The differences in the patterns of drug
      use at each hospital may be due to the types of infections encountered and/or the
      ages of the patients, both of which differed greatly. The proportions of
      resistant strains may also be related to differences in the proportions of in
      patients.

PMID- 9027669
TI  - Targeting immunotherapy using the avidin-biotin system for a human colon
      adenocarcinoma in vitro.
AB  - A new method of targeting immunotherapy using the avidin-biotin system in vitro
      was investigated. Both an anti-carcinoembryonic antigen monoclonal antibody (anti
      CEA MAb) and an anti-cancer drug, neocarzinostatin (NCS), were biotinylated. A
      human colon adenocarcinoma cell line (LoVo) was immunized with biotinylated anti
      CEA MAb; avidin was added, and the cell line was incubated with various
      concentrations of biotinylated NCS for either 72 h or 7 min. In the incubation
      for 72 h, the IC50 was similar (approximately 0.45 microgram/ml) for biotinylated
      NCS for LoVo cells immunized with biotinylated anti-CEA MAb and those without
      immunization. In the incubation for 7 min, the IC50 (concentration producing 50%
      cytotoxicity) of biotinylated NCS for LoVo cells immunized with biotinylated anti
      CEA MAb (0.35 microgram/ml) was five times less than that of non-immunized LoVo
      cells (1.8 micrograms/ml). Thus the present system has the potential to reduce
      the dosage of anti-cancer drugs needed, and this strategy seems likely to be a
      valuable clinical tool in targeting immunotherapy.

PMID- 9027670
TI  - Citalopram causes no significant alterations in plasma neuroleptic levels in
      schizophrenic patients.
AB  - Steady-state plasma concentrations of commonly used neuroleptic drugs were
      measured in 90 schizophrenic patients before and after adding placebo or
      citalopram (40 mg/day) to their treatment regimen. Plasma concentrations of
      citalopram and its main metabolite, desmethylcitalopram, were also measured. In
      addition, patients with exceptionally high neuroleptic levels or an increase in
      adverse effects during the 12-week study period were evaluated for their
      debrisoquine/sparteine hydroxylase (CYP2D6) genotype, an enzyme responsible for
      oxidative metabolism of several neuroleptics and selective serotonin re-uptake
      inhibitors. There were no significant changes in plasma concentrations of
      haloperidol, chlorpromazine, zuclopenthixol, levomepromazine, thioridazine or
      perphenazine during the study. Plasma concentrations of citalopram and
      desmethylcitalopram were well within the levels reported previously with
      monotherapy, and remained stable throughout the study. None of the 15 patients
      analysed for the CYP2D6 genotype was a poor metabolizer. It is concluded that
      clinically important pharmacokinetic drug interactions do not play a crucial role
      when citalopram is used as an augmentation therapy in neuroleptic-treated
      schizophrenic patients.

PMID- 9027671
TI  - Dirithromycin versus amoxiclav in the treatment of acute exacerbations of chronic
      bronchitis.
AB  - A total of 334 patients with acute exacerbation of chronic bronchitis were
      treated with either dirithromycin for 5 days (n = 169) or amoxiclav for 7-10 days
      (n = 165) in an open randomized trial. The efficacy and tolerability of the two
      drugs were compared. There was no statistically significant difference in outcome
      between the two treatment arms. Clinical success (cure or improvement) was
      obtained in 94.5% and 93.1% of patients treated with dirithromycin and amoxiclav,
      respectively. Adverse events (mostly gastrointestinal) occurred in both groups,
      but led to discontinuation of treatment (in only seven patients). We conclude
      that the two drugs are equally efficacious and safe.

PMID- 9027672
TI  - Transdermal nitroglycerine in the management of pain associated with primary
      dysmenorrhoea: a multinational pilot study. The Transdermal
      Nitroglycerine/Dysmenorrhoea Study Group.
AB  - Endogenous nitric oxide mediates smooth-muscle relaxation with subsequent
      vasodilatation in the vascular, pulmonary, gastrointestinal and genitourinary
      tissues. Transdermal nitroglycerine (a nitric oxide donor) has been found
      effective in inhibiting uterine contractility during premature labour. Sixty-five
      women with histories of moderate-to-severe pain associated with menses were
      treated with nitroglycerine patches that delivered 0.2 or 0.1 mg/h. Patches were
      applied as necessary during the first 3 days of the menstrual cycle for up to
      three consecutive cycles. Pain intensity was assessed at baseline and at 30 min
      and at 1, 2 and 4 h after patch application. Most patients obtained pain relief
      with the first dose of the first day. Pain relief was satisfactory to excellent
      in 90% of the patients. Headache was reported by 20% of the patients, most often
      in patients using two consecutive patches. A randomized, double-blind, placebo
      controlled study is underway in an attempt to confirm the above findings.

PMID- 9027673
TI  - Health economics with retrospective data: selection bias issues.

PMID- 9027674
TI  - Congenital ocular aberrant innervation--new concepts.
AB  - BACKGROUND: We have the impression that congenital aberrant innervations are more
      common than previously reported. Many varieties exist and typically involve the
      sixth nerve. The most common ocular miswirings are Duane's syndrome and Marcus
      Gunn jaw-winking ptosis. The second most common miswiring involves lateral rectus
      activation in upgaze causing a "Y" pattern exotropia (pseudo inferior oblique
      overaction). This commonly is confused with inferior oblique overaction but
      surgery on the obliques does not cure the condition. Lateral rectus recession and
      elevation are required. METHODS: We selected demonstrative cases from our
      practices to illustrate a variety of congenital aberrant innervations. A
      literature search for previous reported cases of aberrant innervations was
      performed. This report is an eclectic collection of observations of individual
      selected cases. RESULTS: We found aberrant innervations of unusual varieties.
      These miswirings involve simultaneous firing of the lateral rectus with other
      muscles, including: the ipsilateral superior rectus, causing "pseudo inferior
      oblique overaction"; the contralateral lateral rectus, causing synergistic
      divergence; the ipsilateral superior rectus, in upward saccades only; and the
      masticatory muscles, causing exotropia with sucking. The third nerve by itself
      rarely is involved in congenital miswirings, but commonly shows aberrant
      regeneration after traumatic injuries. We know of no cases of aberrant
      innervation involving the fourth nerve. SUMMARY: We present cases describing
      these congenital aberrant innervations and discuss a unifying hypothesis as to
      their typical involvement of the sixth nerve.

PMID- 9027675
TI  - Fundus morphology assessed by digital image analysis in children with fetal
      alcohol syndrome.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) is associated with anomalies of the eye
      ground. The aim of this study was to evaluate the development of fundus
      morphology in children with FAS from early childhood to adolescence. METHODS:
      Funds photographs were evaluated by digital image analysis in 16 children with
      FAS. Age at the baseline study was between 0.25 and 14 years, and the median
      follow-up period was 7 years (range: 0.5 to 12). Sixteen sex- and age-matched
      healthy children were used as controls. RESULTS: Children with FAS had a smaller
      optic disc area, lower frequency of excavations, greater tortuosity of retinal
      vessels, and a smaller number of vascular branching points compared with the
      controls. There were no significant differences in the funds abnormalities
      between the first and last examinations. CONCLUSION: No interval change of
      retinal funds morphology was found at follow up, suggesting that the ocular
      abnormalities associated with FAS remain unchanged during childhood.

PMID- 9027676
TI  - Comparison of the HOTV and Lea Symbols charts for preschool vision screening.
AB  - PURPOSE: Two preliterate acuity charts, the Lea Symbol chart and the HOTV chart,
      were compared prospectively in an established preschool vision screening program.
      The charts were compared by measuring time required to test, reliability
      coefficients, and the percentage of children testable with each chart. METHODS
      AND MATERIALS: Seven hundred and seventy-seven 3- to 5-year-old children were
      randomized to four screening sequences that determined the order of chart use.
      Each child was screened on two occasions within 6 weeks. Testing was performed at
      10 feet, and optotypes were not isolated for testing. RESULTS: Mean test time was
      significantly less for older children, but was not related to the chart used.
      Reliability coefficients were similar for the Lea Symbols and the HOTV charts.
      The percentage of children testable by each chart improved with increased age of
      the child. More 3 year olds were testable with the Lea Symbols chart compared to
      the HOTV chart (92% versus 85%, P = .05). CONCLUSIONS: Vision screening with
      either chart was more rapid and more frequently achieved with 4- and 5-year-old
      children compared with the 3 year olds. For the population as a whole, each chart
      gave similar results. Among the 3 year olds, however, testability rates were
      better for the Lea Symbols chart. The Lea Symbols chart is an acceptable option
      for preschool vision screening, and may be more efficacious than the HOTV chart
      for screening 3-year-old children.

PMID- 9027677
TI  - Magnetic resonance imaging in evaluation of congenital and acquired superior
      oblique palsy.
AB  - BACKGROUND: According to the recently popularized classification of superior
      oblique (SO) palsy based on congenital variations of the tendon, the primary
      pathology is the abnormality of the SO tendon rather than an innervational
      problem in congenital cases. If this hypothesis is true, denervation atrophy of
      SO muscle should not occur in patients with congenital SO palsy. METHODS: Eight
      patients with traumatic and nine patients with definite congenital SO palsy
      underwent magnetic resonance imaging (MRI) of the orbit. SO muscle width and
      cross-sectional area measurements were taken from coronal images and compared
      with the clinically uninvolved superior oblique muscles. RESULTS: Atrophy of
      varying degrees was observed in the SO muscle both in congenital and acquired
      cases. No significant difference was found in the appearance of the SO muscle
      between acquired and congenital SO palsy groups. CONCLUSION: We have been unable
      to demonstrate abnormalities of the SO tendon in both groups. The MRI appearance
      of the SO muscle suggested that in congenital SO palsy, the pathology is not
      limited to the tendon; there also is an abnormality of the muscle itself.

PMID- 9027678
TI  - Congenital aphakia: a clinicopathologic report of three cases.
AB  - BACKGROUND: Congenital aphakia is a rare condition that has been classified as
      primary when no lens induction of the surface ectoderm occurs and secondary when
      lens development takes place but later is resorbed or expelled in utero. METHODS:
      The authors report the clinical and pathologic findings in three infants with
      congenital aphakia whose eyes were enucleated either at surgery at 11 months or
      at autopsy after 1 and 3 days of life. RESULTS: Two cases classified as primary
      congenital aphakia had severe microphthalmos, anterior segment aplasia, or
      anomalous development and posterior choroidal and optic disc colobomas. One was
      in a case believed to be Waardenburg's recessive anophthalmia syndrome and the
      other had 18 trisomy. A case of secondary congenital aphakia had findings of
      Peter's syndrome and features suggesting rubella, which had been observed in some
      previous reports. CONCLUSIONS: Primary congenital aphakia can result from a
      variety of teratogenic events in the first 4 weeks of embryogenesis and results
      in microphthalmos and severe anterior segment aplasia/dysplasia. Secondary
      congenital aphakia is associated with less severe ocular anomalies. The possible
      role of deletion or mutation involving the PAX6 gene in anterior segment
      anomalies and induction of lens development is discussed. In addition to
      chromosomal influences, in utero viral infection, particularly rubella, may play
      a role in some cases.

PMID- 9027679
TI  - Necrotic melanocytoma of the choroid in a 2-year-old child.

PMID- 9027680
TI  - Diagnosis and management of iris juvenile xanthogranuloma.
AB  - BACKGROUND: Juvenile xanthogranuloma is a benign, self-limiting cutaneous
      disorder most commonly encountered during infancy. Approximately 10% of cases may
      develop ocular or adnexal involvement, most commonly in the iris. METHODS: We
      review clinical and morphological features of four cases of iris juvenile
      xanthogranuloma that reflect the diagnostic and therapeutic spectrum. RESULTS:
      Tissue diagnosis was confirmed in all cases; in one case, the disease was
      diagnosed with a skin biopsy and treated with local and systemic steroids, and
      its persistence in the iris was confirmed with a second tissue specimen obtained
      five months after systemic steroid treatment. CONCLUSION: The diagnosis and
      treatment of juvenile xanthogranuloma may be straightforward, particularly in
      cases when the ocular lesion receives early attention and responds well to
      topical steroids, and when there is no hyphema. However, in other instances, this
      entity may be difficult to manage and may necessitate iris biopsy for diagnosis
      and radiation therapy for treatment.

PMID- 9027681
TI  - Suppression of vestibular nystagmus by forced convergence in normal human
      subjects.
AB  - BACKGROUND: It has been suggested that the principal mechanism of nystagmus
      suppression in the nystagmus blockage syndrome is either adduction of the eye or
      convergence. We examined this issue using the nystagmus of the vestibulo-ocular
      reflex (VOR) as a model. METHODS: A motorized, computer-controlled rotary chair
      was used to produce VOR in darkness, using either sinusoidal or velocity step
      stimulation. Left eye position was monitored and horizontal slow-phase eye
      velocity was calculated. Subjects were cued to converge or perform other gaze
      tasks. RESULTS: Convergence suppressed nystagmus. With sinusoidal stimulation,
      nystagmus was nearly extinguished in extreme lateroversion, probably due to
      mechanical tethering of the eye. However, VOR gain suppression of 47% during
      convergence was observed even when the monitored eye was close to primary
      position. With velocity step stimulation, nystagmus was nearly extinguished at
      moderate angles of adduction. CONCLUSIONS: Convergence is sufficient to suppress
      nystagmus, without vision and without regard to whether the eye is adducted.

PMID- 9027682
TI  - Subnormal binocular vision in the Williams syndrome.
AB  - PURPOSE: Patients with Williams syndrome have been found to have a high
      prevalence of strabismus. This may be due to a primary sensory abnormality. The
      purpose of this study was to determine the prevalence of subnormal binocular
      vision in patients with Williams syndrome. METHODS: Patients being followed in an
      interdisciplinary Williams syndrome clinic were prospectively evaluated to
      determine their binocular status. RESULTS: Eleven patients with Williams syndrome
      underwent an ophthalmologic evaluation. Twenty-seven percent of patients had
      strabismus (3/11). Eight patients demonstrated no measurable strabismus. Six of
      these patients were found to have monofixation syndrome. CONCLUSIONS: There is a
      high prevalence of subnormal binocular vision in Williams syndrome. This
      subnormal binocular vision may explain the high prevalence of strabismus in this
      syndrome.

PMID- 9027683
TI  - Periorbital solitary-type infantile myofibromatosis.

PMID- 9027684
TI  - Orbital hemorrhage following extracorporeal membrane oxygenation in a newborn.

PMID- 9027685
TI  - Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white
      tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus
      nelsoni) in northcentral Colorado.
AB  - Between March 1981 and June 1995, a neurological disease characterized
      histologically by spongiform encephalopathy was diagnosed in 49 free-ranging
      cervids from northcentral Colorado (USA). Mule deer (Odocoileus hemionus) were
      the primary species affected and accounted for 41 (84%) of the 49 cases, but six
      Rocky Mountain elk (Cervus elaphus nelsoni) and two white-tailed deer (Odocoileus
      virginianus) were also affected. Clinical signs included emaciation, excessive
      salivation, behavioral changes, ataxia, and weakness. Emaciation with total loss
      of subcutaneous and abdominal adipose tissue and serous atrophy of remaining fat
      depots were the only consistent gross findings. Spongiform encephalopathy
      characterized by microcavitation of gray matter, intraneuronal vacuolation and
      neuronal degeneration was observed microscopically in all cases. Scrapie
      associated prion protein or an antigenically indistinguishable protein was
      demonstrated in brains from 26 affected animals, 10 using an immunohistochemical
      staining procedure, nine using electron microscopy, and seven using Western blot.
      Clinical signs, gross and microscopic lesions and ancillary test findings in
      affected deer and elk were indistinguishable from those reported in chronic
      wasting disease of captive cervids. Prevalence estimates, transmissibility, host
      range, distribution, origins, and management implications of spongiform
      encephalopathy in free-ranging deer and elk remain undetermined.

PMID- 9027686
TI  - Epizootiology of morbillivirus infection in harp, hooded, and ringed seals from
      the Canadian Arctic and western Atlantic.
AB  - Using a virus neutralization technique, we found phocine distemper virus (PDV)
      antibody in 130 (83% of 157) harp seals (Phoca groenlandica) from the western
      North Atlantic sampled between 1988 and 1993 inclusive. In contrast, only 44 (24%
      of 185) hooded seals (Cystophora cristata) had antibodies against PDV even though
      they were sympatric with harp seals and were sampled over a similar period, from
      1989 to 1994 inclusive. Antibodies occurred in 106 (41%) of 259 ringed seals
      (Phoca hispida); this prevalence was higher than expected given the solitary
      behavior and territoriality characteristic of this species. Seropositive ringed
      seals were found at each of seven locations across Arctic Canada from Baffin Bay
      to Amundsen Gulf at which samples were collected between 1992 and 1994. However,
      the prevalence of infection was highest where ringed seals are sympatric with
      harp seals in the eastern Canadian Arctic.

PMID- 9027687
TI  - Surveillance and spatiotemporal associations of rabies in rodents and lagomorphs
      in the United States, 1985-1994.
AB  - Between 1985 and 1994, 368 cases of rabies in rodents (95% of reports) and
      lagomorphs (5%) were reported to the Centers for Disease Control and Prevention,
      Atlanta, Georgia (USA), from 22 states. This was a 354% increase from the period
      1971 to 1984. Most reports were cases of rabies in woodchucks (Marmota monax) (n
      = 317), primarily from the eastern United States, which has been recently
      experiencing an epizootic of raccoon (Procyon lotor) rabies. Cases of rabies in
      woodchucks were temporally and spatially associated with reports of raccoon
      rabies. Antigenic or genetic characterization of variants of rabies viruses from
      rodents and woodchucks corresponded to the variants associated with the major
      terrestrial wildlife reservoir within the geographic region of specimen origin.
      Although rodents and lagomorphs are infrequently infected with rabies and human
      contact with these animals rarely requires postexposure treatment, appropriate
      health authorities need to evaluate individual circumstances surrounding
      potential exposures.

PMID- 9027688
TI  - Tick-raccoon associations and the potential for Lyme disease spirochete
      transmission in the coastal plain of North Carolina.
AB  - Raccoons (Procyon lotor) were live-trapped and examined for ticks from July 1990
      to July 1993 in the coastal plain of North Carolina on Marine Corps Base, Camp
      Lejeune, North Carolina (USA). Five species of ixodid ticks were found on 351
      (78%) of 449 raccoons. Amblyomma americanum was the most abundant tick found on
      raccoons. Dermacentor variabilis, Ixodes texanus, and Ixodes scapularis were
      frequently collected, while Ixodes cookei were rarely collected from raccoons.
      Tick burdens were not affected by the age, sex, or trap location of captured
      raccoons. Ticks parasitizing raccoons had varying seasonal patterns of abundance.
      Amblyomma americanum were generally collected from raccoons year around, but
      infestation intensities were greatest in summer from June to September.
      Dermacentor variabilis adults were most abundant in mid-summer while peak numbers
      of larvae were collected in the fall. Infestation intensities of Ixodes texanus
      larvae were greatest in fall and winter months while nymphs were most abundant in
      winter and spring. No males were collected from raccoons, but females were most
      frequently collected in the spring and declined in abundance in the summer with
      no specimens collected in the fall or winter. Numbers of 1. scapularis adults
      appeared to reach peak numbers in the fall while larvae and nymphs were most
      abundant on raccoons in winter. Spirochetes, Borrelia burgdorferi, were
      identified in a small percentage (0.2%) of host-seeking A. americanum nymphs and
      adults, and I. scapularis adults by immunofluorescent antibody assays. Similarly,
      a small percentage (1.9%) of host-associated A. americanum, D. variabilis, I.
      texanus and I. cookei contained B. burgdorferi. Borrelia burgdorferi spirochetes
      were cultured from the blood of 23 (26%) of 87 raccoons.

PMID- 9027689
TI  - Role of the eastern chipmunk (Tamias striatus) in the epizootiology of Lyme
      borreliosis in northwestern Illinois, USA.
AB  - The role of the eastern chipmunk (Tamias striatus) in the epizootiology of Lyme
      borreliosis was evaluated in Castle Rock State Park, Illinois (USA), an enzootic
      region, from June to August 1993. Prevalence, intensity, and molting rate of
      immature Ixodes scapularis were determined for chipmunks, white footed mice
      (Peromyscus leucopus), and raccoons (Procyon lotor). Chipmunks were the primary
      host for I. scapularis nymphs and an important secondary host for I. scapularis
      larvae. Based upon ear punch biopsy analysis, B. burgdorferi prevalence in
      chipmunks was similar to that of mice in August and greater than that of mice in
      June and July. Thus we propose that chipmunks are the primary source of B.
      burgdorferi infection for I. scapularis nymphs and an important secondary source
      of infection for larvae.

PMID- 9027690
TI  - Serological survey for diseases in free-ranging coyotes (Canis latrans) in
      Yellowstone National Park, Wyoming.
AB  - From October 1989 to June 1993, we captured and sampled 110 coyotes (Canis
      latrans) for various diseases in Yellowstone National Park, Wyoming (USA).
      Prevalence of antibodies against canine parvovirus (CPV) was 100% for adults (>
      24 months old), 100% for yearlings (12 to 24 months old), and 100% for old pups
      (4 to 12 months old); 0% of the young pups (< 3 months old) had antibodies
      against CPV. Presence of antibodies against canine distemper virus (CDV) was
      associated with the age of the coyote, with 88%, 54%, 23%, and 0% prevalence
      among adults, yearlings, old pups, and young pups, respectively. Prevalence of
      CDV antibodies declined over time from 100% in 1989 to 33% in 1992. The
      prevalence of canine infectious hepatitis (ICH) virus antibodies was 97%, 82%,
      54%, and 33%, for adults, yearlings, old pups, and young pups, respectively. The
      percentage of coyotes with ICH virus antibodies also declined over time from a
      high of 100% in 1989 to 31% in 1992, and 42% in 1993. Prevalence of antibodies
      against Yersinia pestis was 86%, 33%, 80%, and 7%, for adults, yearlings, old
      pups, and young pups, respectively, and changed over time from 57% in 1991 to 0%
      in 1993. The prevalence of antibodies against Francisella tularensis was 21%,
      17%, 10%, and 20%, for adults, yearlings, old pups, and young pups, respectively.
      No coyotes had serologic evidence of exposure to brucellosis, either Brucella
      abortus or Brucella canis. No coyotes were seropositive to Leptospira interrogans
      (serovars canicola, hardjo, and icterohemorrhagiae). Prevalence of antibodies
      against L. interrogans serovar pomona was 7%, 0%, 0%, and 9%, for adults,
      yearlings, old pups, and young pups, respectively. Antibodies against L.
      interrogans serovar grippotyphosa were present in 17% of adults and 0% of
      yearlings, old pups, and young pups. Many infectious canine pathogens (CPV, CDV,
      ICH virus) are prevalent in coyotes in Yellowstone National Park, with CPV
      influencing coyote pup survival during the first 3 months of life; eight of 21
      transmitted pups died of CPV infection in 1992. The potential impact of these
      canine pathogens on wolves (C. lupus) reintroduced to Yellowstone National Park
      remains to be documented.

PMID- 9027691
TI  - Use of body measurements and serum metabolites to estimate the nutritional status
      of mallards wintering in the Mississippi Alluvial Valley, USA.
AB  - We collected mallards (Anas platyrhynchos) from bottomland hardwood habitats on
      the Bayou Meto Wildlife Management Area and the White River National Wildlife
      Refuge, Arkansas County, Arkansas during the winter of 1990 to 1991 to determine
      if measures of physiological condition could be predicted from structural size,
      serum metabolite levels, or from direct measures of carcass composition. Serum
      triglyceride levels were correlated (r = 0.57, P = 0.007) with total body fat in
      males and slightly increased the value (from R2 = 0.64 to 0.76) of intact body
      mass alone for predicting total body fat in males. Overall, however, serum
      metabolites appeared to be poor indicators of the magnitude of nutrient masses in
      mallards. Three potential indices of nutritional status were developed from
      carcass composition data: protein/total ash, fat/ total ash, and fat/fat-free
      body mass. Protein masses of male mallards changed over winter (P = 0.02).
      Consequently, fat-free masses are not constant and represent poor indicators of
      structural size for mallards wintering in the Mississippi Alluvial Valley.

PMID- 9027692
TI  - Plasma haptoglobin levels in threatened Alaskan pinniped populations.
AB  - We evaluated the plasma concentration of the acute phase protein haptoglobin (Hp)
      from Steller sea lions (Eumetopias jubatus) and harbor seals (Phoca vitulina) in
      regions of Alaska (USA) where the populations of these pinnipeds were declining
      and compared the values with concentrations of Hp from the same species in areas
      where the populations were stable. Samples were collected from 1992 through 1994
      at sites in Southeast Alaska, Prince William Sound, the Gulf of Alaska, and the
      Aleutian Islands. Significantly higher levels of Hp were found in the samples
      from the areas of decline compared to those from stable populations. Based on
      these findings, we propose that one may be able to distinguish these compromised
      pinniped populations using Hp as a biomedical indicator.

PMID- 9027693
TI  - A practical anesthesia monitoring protocol for free-ranging adult African
      elephants (Loxodonta africana).
AB  - Twenty free-ranging adult African elephants (Loxodonta africana) in northern
      Botswana were immobilized with a mean (+/- SD) of 9.5 +/- 0.5 mg etorphine
      hydrochloride and 2,000 IU hyaluronidase by intramuscular (IM) dart. The mean
      time to recumbency was 8.7 +/- 2.4 min. All animals were maintained in lateral
      recumbency. The anesthesia monitoring protocol included cardiothoracic
      auscultation; palpation of auricular pulse for quality and regularity; checking
      of rectal temperature, and monitoring of respiratory and heart rates. Results of
      basic physiologic measurements were similar to those of previous field studies of
      African elephants immobilized with etorphine or etorphine-hyaluronidase. In
      addition, continuous real-time pulse rate and percent oxygen saturation of
      hemoglobin (SpO2) readings were obtained on 16 elephants with a portable pulse
      oximeter. Duration of pulse oximetry monitoring ranged from 3 to 24 min (mean +/-
      SD = 8.2 +/- 4.8 min). Differences between minimum and maximum SpO2 values for
      any given elephant ranged from 1 to 6 percentage points, evidence for relatively
      stable trends. The SpO2 readings ranged from 70% to 96% among the 16 elephants,
      with a mean of 87.3 +/- 2.8%. Fifteen of 16 elephants monitored with a pulse
      oximeter had mean SpO2 values > or = 81 +/- 2.4%, with 11 having mean SpO2 values
      > or = 85 +/- 1.5%. All 20 animals recovered uneventfully following reversal:
      diprenorphine at 23.3 +/- 1.5 mg intravenous (IV) with 11.7 +/- 0.5 mg IM, or 24
      mg diprenorphine given all IV.

PMID- 9027694
TI  - Shell disease in river cooters (Pseudemys concinna) and yellow-bellied turtles
      (Trachemys scripta) in a Georgia (USA) lake.
AB  - A disfiguring shell disease was detected in river cooters (Pseudemys concinna)
      and yellow-bellied turtles (Trachemys scripta) from Lake Blackshear, Georgia
      (USA). The turtles used were part of a mark-recapture study conducted from
      September 1991 to June 1993. Histologic changes on four turtles included acute
      segmental necrosis of the epidermis, followed by ulceration, necrosis of the
      underlying dermis and dermal bone, and exaggerated remodeling of bone. Additional
      findings included visceral inflammatory lesions and bacterial infection, sepsis
      and marked trematode ova granulomatosis. The cause of the shell lesions was not
      determined.

PMID- 9027695
TI  - Pathology of ocular lesions in free-living moose (Alces alces) from Saskatchewan.
AB  - Clinical signs of impaired vision or neurological disease occurred in seven of 74
      free-living moose (Alces alces) from Saskatchewan, Canada, submitted for necropsy
      between 1969 and 1994. Several lesions were found in each eye, including retinal
      degeneration (seven cases), cataract (six cases), lymphocytic-plasmacytic
      anterior uveitis (six cases), corneal scars (six cases), keratitis (four cases),
      and microphthalmia (one case), but their cause was not determined. Moraxella
      bovis was isolated from the cornea of one moose. Lesions in the brain and spinal
      cord were mild or absent.

PMID- 9027696
TI  - Hindlimb deformities (ectromelia, ectrodactyly) in free-living anurans from
      agricultural habitats.
AB  - High prevalences of hindlimb deformities were recorded in wild-caught green frogs
      (Rana clamitans), northern leopard frogs (Rana pipiens), American toads, (Bufo
      americanus), and bullfrogs (Rana catesbeiana) from agricultural sites exposed to
      pesticide runoff in the St. Lawrence River Valley of Quebec, Canada, between July
      and September 1992 and 1993. Of 853 metamorphosing anurans examined in 14
      farmland habitats, 106 (12%; range 0 to 69%) had severe degrees of ectromelia and
      ectrodactyly, compared to only two (0.7%; range 0 to 7.7%) of 271 in 12 control
      sites. However, the variation in the proportion of deformities among sites was
      too large to conclude that there was a significant difference between control and
      pesticide-exposed habitats. Clinical signs varied and were characterized by
      segmental hypoplasia or agenesis of affected limbs. Conspicuous abnormalities
      interfered with swimming and hopping, and likely constituted a survival handicap.
      Because of circumstances and the frequency of these malformations in nine
      distinct habitats, and in three different species from one of our study sites, we
      propose a teratogenic action of exogenous factors. Despite the fact that many
      biotic and abiotic agents are potentially harmful to limb development,
      agricultural contaminants were suspected as primary aggressors. Thus, clinical
      examination and frequency of deformities in anurans might be an economical
      screening tool to assess ecosystem health and the presence of environmental
      contaminants.

PMID- 9027697
TI  - Pathology of mucormycosis of cane toads in Australia.
AB  - The gross and microscopic pathology of a fungal septicaemia caused by the
      zygomycete. Mucor amphibiorum in 27 free-ranging cane toads, Bufo marinus, in
      Australia is described. Seven of the 27 toads had clinical signs of illness when
      discovered and five of these seven were moribund. Multiple granulomas were found
      in many organs, and in massive infections granulomas tended to coalesce. Liver,
      spleen, kidneys, urinary bladder, heart and lung were most commonly involved, but
      granulomas also occurred in subcutaneous lymph spaces, skin, gastro-intestinal
      tract, voluntary muscle, bone, cranial cavity and the oral cavity. Single lesions
      appeared grossly as a lemon coloured nodule < or = 5 mm in diameter.
      Histologically, the primary lesion was a granuloma composed of multinucleate
      giant cells, macrophages, occasional lymphocytes and eosinophils surrounding the
      distinctive sphaerules of M. amphibiorum. Fibroblasts occurred in greater numbers
      at the periphery and collagen formed a dense fibrous capsule around some nodules.
      A less common lesion resembled a microabscess and consisted of mononuclear cells,
      neutrophils and eosinophils surrounded by macrophages. Many of the centrally
      placed mixed inflammatory cells appeared necrotic. This reaction appeared to be
      more acute. Both types of lesions sometimes occurred concurrently, but the latter
      was less common. The pattern of lesions and natural history of M. amphibiorum
      suggested that ingestion of contaminated soil may have been the route of
      infection.

PMID- 9027698
TI  - Evaluation of low-level aflatoxin in the diet of white-tailed deer.
AB  - We evaluated the response of white-tailed deer (WTD) (Odocoileus virginianus) to
      dietary aflatoxin. Fourteen 4-to-5-mo-old WTD were used in this 8-wk study,
      conducted between November 1993 and January 1994. Seven animals received a ration
      containing 800 parts per billion (ppb) total aflatoxin (AF). Seven control
      animals received the same ration without AF. At 0, 1, 3, 6 and 8 wk, feed
      consumption, feed conversion, liver enzymes, bile acid levels, and immune
      function via lymphocyte proliferation assays and delayed type hypersensitivity
      reactions were determined. At the conclusion of the 8-wk feeding trial, deer were
      euthanized and necropsied. Clinical illness was not evident in any of the
      animals, but by the end of the study, AF-fed deer had reduced feed consumption
      and body weight as compared to control deer; the differences were not
      statistically significant. The AF-exposed group had a significant increase (P =
      0.03) in serum bile acid concentration as compared to control deer. Two AF
      exposed deer had gross and histologic hepatic lesions indicative of a mild
      degenerative hepatopathy. Residues of an aflatoxin metabolite, aflatoxin M1, were
      found in the livers of all treated animals. No differences in immune function
      were detected between the two groups. We conclude that consumption of 800 ppb AF
      in the diet of young WTD over an 8-wk period can produce subclinical hepatic
      injury.

PMID- 9027699
TI  - Clinicopathological features and histopathology of experimental hepatic
      capillariasis in muskrats (Ondatra zibethicus).
AB  - Ten muskrats (Ondatra zibethicus) each were infected with 17,000 eggs (long-term
      study) and eight muskrats each were infected with 8,000 eggs (short-term study)
      of Capillaria hepatica (Nematoda). Food intake, body weight, and selected
      clinicopathological parameters were measured every 2 days for 28 days in the
      short-term study and every 14 days for 184 days in the long-term study. Muskrats
      in the short-term study had moderate to severe necrotizing granulomatous
      hepatitis associated with mild anorexia and weight loss, varying degrees of
      leukocytosis with eosinophilia and elevation of serum alanine and aspartate
      aminotransferases. No significant changes in packed cell volume, hemoglobin,
      total plasma protein, albumin, blood urea nitrogen, bilirubin, lactate
      dehydrogenase or alkaline phosphatase were found among animals from the short
      term study. Muskrats in the long-term study had severe necrotizing granulomatous
      hepatitis associated with marked anorexia, weight loss and 60% mortality over 39
      days post-inoculation (PI); animals that survived for 184 days did not return to
      pre-inoculation body weights despite returning to normal food intake. Hepatic
      lesions at 184 days PI consisted of minimal to severe liver replacement by C.
      hepatica eggs. No statistically significant differences in values of clinical
      parameters between inoculated animals and a non-inoculated control group from the
      long term study were found.

PMID- 9027700
TI  - An epizootic of lead poisoning in greater flamingos (Phoenicopterus ruber roseus)
      in Spain.
AB  - During November 1992 to March 1993, and November 1993 to February 1994, 106
      greater flamingos (Phoenicopterus ruber) were collected dead or moribund in the
      wetlands of El Fondo and Salinas de Santa Pola, eastern Spain. Birds still alive
      were emaciated and had a bile-stained diarrhea. On necropsy, they had liquid in
      the upper digestive tract and the walls of their gizzards were stained dark
      green. Fifty-three (93%) of 57 gizzards examined contained lead shot (range one
      to 277 shot), and fifty-five (96%) of 57 livers contained levels of lead greater
      than 5 micrograms/g dry weight (DW) (median = 192.3 micrograms/g DW, range < 2.5
      to 992.2 micrograms/g DW).

PMID- 9027701
TI  - Lead toxicosis in a captive bottlenose dolphin (Tursiops truncatus) consequent to
      ingestion of air gun pellets.
AB  - A captive bottlenose dolphin (Tursiops truncatus) in a dolphinarium in Tel Aviv,
      Israel, had signs of anorexia, weight loss and a reluctance to train over a 4
      week period in June 1995 and died shortly thereafter. On necropsy, it had an
      enlarged, yellow discolored liver, and about 55 air gun pellets in the second
      stomach. The pellets were composed of 40% lead. Samples of liver and kidney
      cortex contained 3.6 and 4.2 micrograms/g lead, respectively. There was
      hemosiderosis in the liver and kidneys, status spongiosus in the brain, and
      vacuolization in the optic nerve; acid-fast intranuclear inclusion bodies were
      seen in the kidneys. We propose that chronic lead toxicosis had been induced
      after the gradual dissolution of the lead-based pellets in the acid environment
      of the stomach.

PMID- 9027702
TI  - Malignant mast cell tumor in an African hedgehog (Atelerix albiventris).
AB  - In November 1995, a malignant mast cell tumor (mastocytoma) was diagnosed in an
      adult African hedgehog (Atelerix albiventris) from a zoological park (West
      Lafayette, Indiana, USA). The primary mast cell tumor presented as a firm
      subcutaneous mass along the ventrum of the neck. Metastasis to the right
      submandibular lymph node occurred.

PMID- 9027703
TI  - An indirect immunofluorescent test for detection of rabies virus antibodies in
      foxes.
AB  - The blood-containing fluids in the thoracic cavity or blood from the heart from
      177 red foxes (Vulpes vulpes) in Slovenia were evaluated for rabies antibodies by
      rapid fluorescent focus inhibition test (RFFIT) and an adapted indirect
      immunofluorescent test (IIF) in 1994. We evaluated the usefulness of anti-dog
      fluorescein-isothiocyanate (FITC) conjugate instead of anti-fox FITC conjugate in
      detection of antibodies against rabies virus in fox sera. In the RFFIT test, 92
      (52%) of the fox samples were positive and 70 (40%) samples were negative for
      rabies antibodies; 15 (8.5%) samples were not suitable for examination in this
      test. In the IIF test, 98 (55%) fox samples were positive and 79 (45%) sera were
      negative. The IIF test was suitable for the rapid detection of antibodies against
      rabies virus in foxes, as often required for vaccine efficacy trials.

PMID- 9027704
TI  - Bacterial survival, lymph node pathology, and serological responses of bison
      (Bison bison) vaccinated with Brucella abortus strain RB51 or strain 19.
AB  - From August 1993 to June 1994, 3 month-old bison (Bison bison) were vaccinated
      with Brucella abortus strain RB51 (SRB51, n = 6), strain 19 (S19, n = 3), or with
      saline (n = 1) and serologic responses and persistence of vaccine strains within
      lymph nodes were monitored. Bison vaccinated with S19 had granulomatous
      lymphadenitis and greater peak numbers of B. abortus than those vaccinated with
      SRB51. Bison vaccinated with RB51 had similar histological lesions and B. abortus
      were still present in lymph nodes at 16 weeks. Although antibodies against RB51
      were produced, standard tube agglutination test responses of RB51-vaccinates
      remained negative. The histological lesions of B. abortus infections in bison
      were similar to those observed in cattle, but bison did not clear SRB51 as
      rapidly as cattle.

PMID- 9027705
TI  - Mortality in black siskins (Carduelis atrata) with systemic coccidiosis.
AB  - Ninety-five (97%) of 98 black siskins (Carduelis atrata) died within 2 months of
      arrival in Italy from South America with the following clinical sings: rapid
      weight loss, breast muscle atrophy, congested and distended abdomen, diarrhea,
      and lethargy. Macroscopically we observed hepato-splenomegaly, pulmonary
      congestion, and thickening of the interstinal wall. Histologically,
      lymphomonocytic transmural enteritis, interstitial mononuclear cell infiltrates
      in the lungs and in the liver, as well as activation of splenic follicles were
      common features. Large numbers of protozoa belonging to Isospora sp. were
      observed in various stages of their life-cycle in the intestinal epithelium, and
      some zoites were found in the extra-intestinal cellular infiltrate as well. No
      viral or bacterial pathogens were found.

PMID- 9027706
TI  - Baylisascaris sp. found in a wild northern bobwhite (Colinus virginianus).
AB  - During a telemetry study conducted between 1993 and 1995 in east-central Kansas
      (USA) on northern bobwhite (Colinus virginianus) populations, a wild adult male
      quail was found with signs of disorientation and torticollis in August 1994 in
      Lyon County, Kansas. Based on histological and parasitological examination, it
      was determined that the bird was infected with larval nematodes of the genus
      Baylisascaris spp. This is the first known recorded case of Baylisascaris sp. in
      a wild game bird species.

PMID- 9027707
TI  - Immobilization of collared peccaries (Tayassu tajacu) and feral hogs (Sus scrofa)
      with Telazol and xylazine.
AB  - A 1:1 mg mixture of Telazol and xylazine hydrochloride (100 mg of Telazol and 100
      mg of xylazine per ml) was used to immobilize wild collared peccaries (Tayassu
      tajacu) and feral hogs (Sus scrofa); mean (+/-SD) intramuscular dosage rate was
      4.73 +/- 0.86 mg/kg and 4.35 +/- 0.68 mg/kg for peccaries (n = 107) and hogs (n =
      49), respectively. Mean (+/-SD) induction time (time from injection until
      complete immobilization) was 4.6 +/- 2.5 minutes for collared peccaries and 4.4
      +/- 1.9 for hogs. Peccaries became conscious at 64 +/- 29 minutes and first stood
      at 92 +/- 33 minutes after initial injection. Hogs became conscious at 54 +/- 26
      minutes and first stood at 78 +/- 38 minutes after initial injection. A 1:1 mg
      mixture of Telazol and xylazine provided an effective and safe method to
      immobilize both species and provided adequate analgesia and anesthesia for short
      surgical procedures.

PMID- 9027708
TI  - Field immobilization of muskrats (Ondatra zibethicus) for minor surgical
      procedures.
AB  - A combination of ketamine hydrochloride and xylazine hydrochloride at doses of 50
      mg/kg and 5 mg/kg, respectively, was used to immobilize 48 muskrats (Ondatra
      zibethicus) from October 1993 to November 1994 in Tennessee (USA). Mean (+/-SD)
      time for induction was 2.97 +/- 1.1 min. After a mean (+/-SD) duration of 27.2 +/
      3.5 min intramuscular yohimbine hydrochloride at a dose of 0.125 mg/kg was
      administered. Mean (+/-SD) recovery time was 48.1 +/- 21.6 min. All anesthetic
      inductions were smooth and sufficient depth of anesthesia was achieved to allow
      surgical collection of adipose tissue. Recovery times were more variable than
      expected. There was a significant (P < or = 0.05) drop in heart rate, respiratory
      rate, and body temperature during anesthesia. One animal died during recovery.

PMID- 9027709
TI  - Heterogeneities and profiles of oxygen pressure in brain and kidney as examples
      of the pO2 distribution in the living tissue.

PMID- 9027710
TI  - Oxygen and renal metabolism.

PMID- 9027711
TI  - Is tubuloglomerular feedback a tool to prevent nephron oxygen deficiency?
AB  - The purpose of the study was to analyze whether rhythmic oscillations of proximal
      tubular pressure and distal fluid conductivity at the renal surface are induced
      by oxygen deficiency of thick ascending limb (TAL) segments. Oxygen pressure was
      measured in halothane anesthetized Munich-Wistar rats by a multi-wire micro-gold
      electrode at the kidney surface. Signals from wires placed upon glomeruli and
      tubuli exhibited pO2 oscillations with exactly the same frequency (in mean 30
      mHz) as have been described for proximal tubular pressures or distal fluid
      conductivities. This supports our suggestion that a limited oxygen supply to the
      nephron forces TAL segments to oscillate between aerobic and anaerobic energy
      production. A switch to glycolysis reduces TAL's transport efficiency
      dramatically. At the macula densa, the terminal end of the TAL segment, the
      thereby elevated sodium concentration operates as a switch by means of the TGF to
      adapt the filtered load to the oxygen supply of the individual nephron. In this
      way proximal tubules may also be protected from oxygen deficiency, which is
      essential due to their low glycolytic capacity. An enhanced halothane
      concentration of 2% or the use of barbiturates, such as Inactin, blocks
      oscillations completely as furosemide blocks oscillations as well as the feedback
      response. Reduction of the hematocrit by exchange transfusion mainly reduces
      supratubular pO2 values, and to a lesser extent also reduces supraglomerular
      pressures. This demonstrates that oxygen shunt diffusion in the kidney cortex and
      medulla is a prerequisite for both the function of a sensor to measure pO2 and
      oxygen capacity to regulate erythropoietin secretion and to enable an effective
      adjustment of blood flow to the metabolic and functional demands of the kidney.

PMID- 9027712
TI  - Sites of erythropoietin production.

PMID- 9027713
TI  - Role of oxygen in the zonation of carbohydrate metabolism and gene expression in
      liver.
AB  - Hepatocytes around the afferent (periportal) vessels differ from those around the
      efferent (perivenous) vessels in their contents of key enzymes, and therefore
      have different metabolic capacities. Thus, the model of "metabolic zonation"
      proposes that the periportal cells produce glucose via glycogenolysis and
      gluconeogenesis and that the perivenous cells utilize glucose via glycogen
      synthesis and glycolysis. The periportal and perivenous cells receive different
      signal patterns, because substrates including oxygen and hormones are degraded
      and products and mediators are formed during passage of blood through the liver.
      The different signal patterns should be important for both short-term regulation
      of metabolic rates and for long-term induction and maintenance of the enzyme
      equipments by control of gene expression. From the periportal to the perivenous
      zone, the concentration of the signal oxygen falls corresponding to a drop from
      about 13 (arterial) to 9 (mixed periportal) and then to 4 (hepatovenous) volume%
      gas atmosphere. For short-term regulation of metabolism, in perivenous-like cells
      net glucose production measured over a period of two hours was observed below 2%,
      net glycogen synthesis above 4%, and net lactate utilization above 6% oxygen. In
      periportal-like cells net glucose formation and net lactate utilization increased
      sharply from anoxia to 6% oxygen and then only moderately. For long-term
      regulation of gene expression, the glucagon (cAMP)-dependent activation of the
      PCK gene was modulated by oxygen. The transcriptional rate, the abundance of mRNA
      and the enzyme activity were increased to higher levels under arterial rather
      than under venous oxygen. Conversely, the insulin-dependent activation of the
      glucokinase gene was negatively modulated by oxygen. A heme protein appeared to
      be involved in oxygen sensing, since CO mimicked the effects of oxygen on the PCK
      gene. Hydrogen peroxide was produced by hepatocytes as a function of oxygen
      tension; exogenously added, it mimicked the effects of oxygen on PCK gene
      induction. Therefore, the heme protein containing an oxygen sensor could be a
      peroxide producing oxidase. It is not known at present whether the same oxygen
      sensor is also involved in the short-term regulation by oxygen of hepatic
      carbohydrate metabolism. Transfection of PCK promoter-CAT gene constructs into
      primary hepatocytes showed that oxygen modulated PCK gene activation in the
      region of -277/+73. This modulation was not mediated by isolated cAMP responsive
      elements.

PMID- 9027714
TI  - Unexpected hypoxia-dependent erythropoietin secretion during experimental
      conditions not affecting tissue oxygen supply/demand ratio.
AB  - Although a great deal of evidence supports the hypothesis that plasma
      erythropoietin (EPO) levels of mammals are related to the oxygen supply to the
      tissues relative to their oxygen needs, several observation millitate against its
      inherent simplicity. This study presents our results obtained from in vivo
      experiments that suggest that hypoxia-dependent EPO production can be altered by
      conditions which apparently do not modify the tissue oxygen supply/demand ratio.
      Hypoxia-dependent EPO production rate (EPO-PR), derived from plasma EPO titers
      and plasma EPO half-lives, were estimated in both transfused-polycythemic and
      normocythemic mouse models subjected to different treatments. From calculations
      of the O2 carrying capacity of blood and body O2 consumption, it was assumed that
      the tissue supply/demand ratios were similar in both experimental and control
      mice of the same model at the time of induction of EPO production. The following
      observations were worth noting: (1) EPO-PRs in transfused polycythemic mice whose
      erythropoietic rates were stimulated by intermittent exposure to hypobaria (0.5
      atm, 18 hr/day x 3 weeks), phenylhydrazine administration (40 mg/kg at weekly
      intervals x 3 weeks) or repeated rh-EPO injections (1500 U/kg 3 times a week x 3
      weeks) before transfusion were more than five times high than in comparabily
      polycythemic mice whose erythropoietic rates were not stimulated previously; and
      (2) EPO-PR in response to hypobaric hypoxia was 2.08 times normal in
      normocythemic mice with cyclophosphamide (100 mg/kg) induced depression of
      erythropoiesis, and 0.33 times normal in normocythemic mice with rh-EPO (400 U/kg
      x 2) induced enhancement of erythropoiesis. Although the results obtained in
      polycythemic mice are difficult to explain, those from normocythemic mice suggest
      the existence of a feedback mechanism between EPO-responsive cells and EPO
      producing cells. Both demonstrate the existence of experimental conditions in
      which modulation of the hypoxia-dependent expression of the EPO gene appears to
      occur. This modulation would be dependent on factors other than oxygen.

PMID- 9027715
TI  - Detection of erythropoietin in human liquor: intrinsic erythropoietin production
      in the brain.
AB  - Until now, erythropoietin (EPO) was thought to be produced exclusively in fetal
      liver and adult kidney and to regulate mammalian erythropoiesis. However, we
      recently showed that steady state levels of EPO mRNA could be induced up to 100
      fold in primary mouse astrocytes cultured under hypoxic conditions, and also
      reported the presence of mRNA for EPO and its receptor in the brain of mouse,
      monkey and human. In extending these studies on humans we now show that
      immunoreactive EPO is present in ventricular cerebrospinal fluid (CSF) of 5
      patients with traumatic brain injuries: EPO was found in 15 out of 15 CSF
      samples. There was no correlation between the serum EPO concentration and the
      concentration in the CSF. However, EPO concentrations in CSF correlated with the
      degree of blood-brain-barrier dysfunction. This suggests that EPO does not cross
      the intact blood-brain-barrier, implying that EPO is produced in the brain
      itself, most probably by astrocytes in an oxygen-dependent manner. In view that
      neuronal cells carry the EPO receptor, we propose that EPO acts in a paracrine
      fashion in the central nervous system and might function as a protective factor
      against hypoxia-induced damage of neurons.

PMID- 9027716
TI  - Hypoxia-induced modulation of endothelial cell properties: regulation of barrier
      function and expression of interleukin-6.
AB  - The endothelial cell response to hypoxia involves a range of adaptive mechanisms
      that reflect an active response of the cell's biosynthetic and metabolic
      apparatus. Hypoxia-mediated suppression of endothelial barrier function,
      resulting in increased vascular leakage, is likely to contribute to pulmonary and
      cerebral edema associated with high altitude and is closely associated with a
      fall in intracellular cyclic AMP levels. Buttressing of this second messenger
      pathway in the endothelium using membrane permeant cyclic AMP analogs prevents
      increased vascular leakage due to hypoxia. Application of this principle to organ
      preservation has shown that supplementation with cyclic AMP analogs or inhibition
      of endogenous cAMP metabolism enables extension of the time a harvested organ can
      remain extracorporeally, after which transplantation is successful. The
      underlying mechanism through which cyclic AMP exerts its effects appears to be
      maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism
      triggered in the endothelium by hypoxia is expression of the cytokine interleukin
      6 (IL-6) by a novel mechanism involving transcription driven by the nuclear
      factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective
      effects on vascular function, thereby limiting vascular injury by a different
      mechanism than those recruited by elevated cAMP levels. These studies provide
      insights into tow independent mechanisms through which endothelium responds to
      oxygen deprivation, and suggest possible new approaches to attentuate vascular
      injury associated with ischemia.

PMID- 9027717
TI  - Endothelial hypoxic stress proteins.

PMID- 9027719
TI  - Effects of hypoxia on growth factor expression in the rat kidney in vivo.
AB  - There is accumulating evidence from in vitro studies suggesting that the genes of
      endothelin-1, PDGF, and VEGF are, like the erythropoietin gene, regulated by
      oxygen tension and by divalent cations. Hypoxia-induced stimulation of, such as
      endothelin-1, PDGF or VEGF might be involved in the pathogenesis of acute or
      chronic renal failure, and in renal "inflammatory" diseases (glomerulonephritis,
      vasculitis, allograft rejection). Hypoxia (8% O2) for six hours caused a 55
      fold/1.6-fold increase of renal erythropoietin/endothelin-1 gene expression,
      whereas endothelin-3, PDGF-A, PDGF-B, and VEGF gene expression was unchanged.
      Carbon monoxide (0.1%) treatment for six hours stimulated renal erythropoietin
      gene expression 140-fold; however, endothelin-1, endothelin-3, PDGF-A, PDGF-B,
      and VEGF gene expression was not affected. Finally, cobalt treatment (60 mg/kg
      CoCl2) increased only renal erythropoietin/PDGF-B gene expression 5-fold/1.65
      fold. These findings suggest that hypoxia is a rather weak stimulus for renal
      endothelin-1 gene expression, and that renal PDGF and VEGF gene expression in
      vivo is not sensitive to tissue hypoxia, in contrast to cell culture experiments.
      The in vivo regulation of endothelin-1, PDGF, and VEGF differs substantially from
      that of erythropoietin, suggesting that the basic gene regulatory mechanisms may
      not be the same.

PMID- 9027718
TI  - Mechanisms by which oxygen regulates gene expression and cell-cell interaction in
      the vasculature.
AB  - Hypoxia has profound effects on blood vessel tone. Acute hypoxia causes pulmonary
      vasoconstriction and chronic hypoxia causes smooth muscle cell replication and
      extracellular matrix accumulation resulting in vessel wall remodeling. The
      cellular responses to hypoxia involve complex cell-cell interactions mediated by
      the release of growth factors, cytokines and biological messengers. We have
      reported that hypoxia increases the expression of a number of genes encoding
      vascular cell mitogens produced by endothelial cells: platelet-derived growth
      factor B (PDGF-B); endothelin-1 (ET-1); and vascular endothelial growth factor
      (VEGF). A 28-bp enhancer in the 5' upstream region of the VEGF gene mediates the
      expression of VEGF by endothelial cells under conditions of hypoxia. Hypoxia,
      however, has opposite effects on the vasodilator nitric oxide (NO); hypoxia
      suppresses both the transcriptional rate of the endothelial nitric oxide synthase
      gene and the stability of its mRNA. These endothelial-dependent processes would
      lead to vessel wall remodeling characteristic of a number of diseases from
      atherosclerosis to pulmonary hypertension. The smooth muscle cell also responds
      to hypoxia. It increases the transcriptional rate of the heme oxygenase gene-1
      responsible for the breakdown of heme to carbon monoxide (CO) and biliverdin. CO
      is a vasodilator with properties similar to the well-studied molecule NO. CO
      suppresses the production of ET-1 and PDGF-B by endothelial cells. The regulated
      production of NO and CO under hypoxia, therefore, results in complex feedback
      loop interactions leading to altered smooth muscle cell growth in an autocrine
      and paracrine manner.

PMID- 9027720
TI  - Induction of VEGF and VEGF receptor gene expression by hypoxia: divergent
      regulation in vivo and in vitro.
AB  - This study examined the expression of EPO, VEGF and VEGF receptor gene under
      conditions of reduced oxygen supply in primary cultures of rat hepatocytes, and
      compared it with the expression of these genes in hypoxic rat livers in vivo. To
      this end we exposed male Sprague-Dawley rats to hypoxia (10% and 8% O2), carbon
      monoxide (0.1% CO) or injected cobalt chloride (60 mg/kg CoCl2) subcutaneously.
      For the in vitro experiments we used primary cultures of rat hepatocytes which
      were kept at high (20% O2) and low (1% O2) oxygen tensions for three hours. The
      EPO mRNA was up-regulated by hypoxia in vitro and in vivo about 10-fold. The VEGF
      mRNA was up-regulated fivefold in the hepatocytes only, whereas the in vivo mRNA
      levels remained unchanged. The mRNA levels of flt-1 were up-regulated threefold
      by 8% O2 in livers, dependent on the strength of hypoxia (10% caused no changes
      in flt-1 gene expression) and on the kind of hypoxic stimulus (8% O2 was as
      effective as 0.1% CO and more effective than cobalt). The mRNA levels of flk
      1/KDR and flt-4 remained unchanged in the liver. In vitro there were no changes
      in the mRNA levels of flt-1, flt-4 and flk-1/KDR. Consequently, the in vivo
      regulation of VEGF, which might be modulated by induction of flt-1 receptor gene
      expression, differs from the in vitro cell culture situation and might be
      different from the EPO regulation in vivo.

PMID- 9027721
TI  - Oxygen sensing by ion channels.

PMID- 9027722
TI  - Diversity of response in vascular smooth muscle cells to changes in oxygen
      tension.
AB  - Hypoxia causes pulmonary vasoconstriction (HPV), but also dilation of systemic
      vessels and the ductus arteriosus. In the adult animal. HPV is initiated by
      inhibition of potassium current (IK) in the smooth muscle cells of small
      resistance arteries, which results in membrane depolarization and calcium entry
      through voltage-gated calcium channels. The oxygen-sensitive channels that
      initiate HPV are 4-aminopyridine (4-AP)-sensitive delayed rectifier channels
      (KDR), the most prominent of which has a conductance of 37 pS. In the fetus,
      hypoxia causes pulmonary vasoconstriction through inhibition of a calcium
      sensitive potassium channel (KCa). In smooth muscle cells from the rabbit ductus
      arteriosus, which dilates in response to hypoxia, whole-cell potassium current is
      reversibly enhanced, rather than inhibited, by hypoxia. The principal oxygen
      sensitive channel is inhibited by 4-AP and has a conductance of about 58 pS.
      There are morphological and electrophysiological differences between individual
      pulmonary artery smooth muscle cells, for example, in some cells IK is
      predominantly carried by KDR channels and in others by KCa channels. KDR cells
      are more common in the resistance pulmonary arteries and KCa in the conduit
      arteries. Responses of specific vessels (conduit, resistance; pulmonary,
      systemic, ductus) at different stages of development (fetal, neonatal and adult)
      to changes in oxygen tension may be determined by the distribution of a variety
      of ion channels in the smooth muscle cells.

PMID- 9027723
TI  - K+ ions and channels: mechanisms of sensing O2 deprivation in central neurons.
AB  - This is an exciting area of research for at least two reasons: (1) it has high
      clinical visibility and potential implications that transcend age, tissue, and
      cell type. (2) Currently there are very powerful armamentaria to solve questions
      and we are starting to apply this in this area of research. Hence, the
      possibility for understanding how hypoxia induces injury or why do cells survive
      anoxia is within reach. I hope that within the foreseeable future we will be able
      to solve some of these questions at the molecular level and start to target some
      of the important pathways for pharmacologic and drug interventions.

PMID- 9027724
TI  - Effects of sodium nitroprusside in the rat cortical collecting duct are
      independent of the NO pathway.
AB  - Recently we described K+ channels in the basolateral membrane of principal cells
      of rat cortical collecting duct (CCD) which are regulated by a cGMP-dependent
      protein kinase (Pflugers Arch 429:338-344, 1995). We examined the effects of the
      NO-liberator sodium nitroprusside (SNP) on single channel activity and membrane
      voltage (Vm) in principal cells of rat CCD, and on transepithelial voltage, lumen
      to-bath Na+ fluxes, and osmotic water permeability in isolated perfused rat CCD
      tubules. While in patch clamp experiments SNP (10 microM) hyperpolarized
      principal cells from -54 +/- 10 mV to -71 +/- 5 mV (N = 5) and increased the
      activity of the described K+ channels from 0.05 +/- 0.03 to 0.45 +/- 0.14 (N = 5)
      in cell-attached and from 0.04 +/- 0.02 to 0.25 +/- 0.05 (N = 4) in excised patch
      clamp experiments, it had no effect on basal or AVP-dependent transepithelial
      voltage, Na+ fluxes, or the osmotic water permeability. In addition, neither 50
      microM SIN-1, another liberator of NO, nor 1 mM L-NAME, an inhibitor of the NO
      synthase, changed Vm significantly. Furthermore, in cGMP-assays SNP failed to
      increase intracellular cGMP in CCD segments. Thus, we conclude that in the rat
      CCD transport is not regulated via the NO-pathway and that SNP acts as an cGMP
      independent activator of K+ channels in the basolateral membrane of these cells.

PMID- 9027725
TI  - ICln, a chloride channel cloned from kidney cells, is activated during regulatory
      volume decrease.

PMID- 9027726
TI  - Immunohistochemical colocalization of the alpha-subunit of neutrophil NADPH
      oxidase and ecto-5'-nucleotidase in kidney and liver.
AB  - In kidney and liver, fibroblasts and fibroblast-like cells, respectively, are
      sources of erythropoietin (Epo) formation, and these cells also bear a number of
      other similarities. Renal Epo expression is localized in peritubular type 1
      fibroblasts of the cortical labyrinth, and in the liver, apart from parenchymal
      cells, transcription is found in Ito cells. Both the renal peritubular cells and
      Ito cells contain ecto-5'-nucleotidase (5'NT). It had been suggested that 5'NT is
      involved in the oxygen sensing mechanism via a hydrolysis of AMP to adenosine,
      which in turn may stimulate EPO synthesis. However, the molecular mechanism of
      the cellular response to hypoxia is currently not well understood. Based on the
      notion that a heme protein probably acts as the oxygen sensor, it has recently
      been proposed that a b-type cytochrome as part of the neutrophil NADPH oxidase
      may influence intracellular superoxide levels depending on local oxygen tension.
      Superoxide levels were otherwise shown to determine the EPO production in
      hepatoma cell lines. By double immunofluorescence labeling the alpha-subunit of
      cytochrome b558 (alpha-SU) and 5'NT were simultaneously localized in rat kidney
      and liver, and in the kidney Epo mRNA and alpha-SU were double-labeled. Positive
      signal for alpha-SU was found in the majority of renal peritubular fibroblasts in
      the cortex and outer medulla, and in Ito cells. In both organs, the cells that
      coexpress 5'NT and Epo mRNA also contain an immunoreactivity for alpha-SU. In
      these cells, cytochrome b558 as part of an NADPH oxidase may be involved in a
      presumptive oxygen sensing mechanism using H2O2 as a possible second messenger
      for EPO gene regulation.

PMID- 9027728
TI  - Cobalt chloride and desferrioxamine antagonize the inhibition of erythropoietin
      production by reactive oxygen species.
AB  - We have recently proposed a H2O2-generating b-type cytochrome as part of the
      cellular oxygen sensor that controls O2-dependent erythropoietin (Epo) production
      in the human hepatocellular carcinoma cell line HepG2. H2O2 could act as an
      intracellular signaling molecule because its production in HepG2 cells is
      strictly dependent on the pericellular PO2. High cellular levels of H2O2 inhibit
      hypoxia-induced Epo production while low levels-as under hypoxic conditions-allow
      full expression of the Epo gene. Since cobalt chloride (CoCl2) and the iron
      chelator desferrioxamine (DSF) both mimic the hypoxic induction of Epo production
      we studied the influence of CoCl2 and DSF on the formation and on the action of
      reactive O2-species with respect to Epo production. Both chemicals reduced the
      H2O2-dependent 123-dihydrorhodamine fluorescence in HepG2 cells. The inhibition
      of Epo production by exogenous H2O2 was completely antagonized by DSF. This might
      indicate that H2O2 exerts its inhibition through a Fenton type reaction. On the
      other hand, NADPH and pyrogallol which stimulate the production of O2- inhibited
      Epo production. CoCl2 antagonized their effects. From our results we propose
      different sites of interaction with the putative signaling chain for DSF and
      CoCl2. While DSF appears to reduce the action of the H2O2 molecule, CoCl2 might
      act further upstream through the induction of H2O2-scavenger systems or by
      interfering with its production.

PMID- 9027727
TI  - Cobalt and desferrioxamine reveal crucial members of the oxygen sensing pathway
      in HepG2 cells.
AB  - Cobalt and desferrioxamine, like hypoxia, stimulate the production of
      erythropoietin in HepG2 cells. It is believed that cobalt as well as
      desferrioxamine interact with the central iron atom of heme proteins by changing
      their redox state similar to hypoxia. A subsequent decrease of the intracellular
      H2O2 levels under hypoxia was presumed to be the key event for stimulating
      erythropoietin production. We therefore investigated whether cobalt and
      desferrioxamine control the intracellular H2O2 levels that regulate gene
      expression by interacting with hemeproteins. Deconvolution of light absorption
      spectra revealed respiratory heme proteins such as cytochrome c, b558 and
      cytochrome aa3, as well as cytochrome b558, which is a nonrespiratory heme
      protein found in HepG2 cells. Whereas respiratory heme proteins are located in
      mitochondria, cytochrome b558 similar to the one described for the neutrophil
      NADPH oxidase can be visualized in the cell membrane of HepG2 cells by
      immunohistochemistry. Incubation with cobalt (100 microM/24 hr) interacts
      predominantly with cytochrome b558 and cytochrome b558. The interaction of cobalt
      with the respiratory chain results in an increased oxygen consumption of HepG2
      cells as revealed by PO2 microelectrode measurements. Desferrioxamine (130
      microM/24 hr), however has no influence on the cytochromes. In response to an
      external application of NADH (1 mM), the membrane bound cytochrome b558 produces
      two times more O2- than to the external NADPH (1 mM) application. Neither
      desferrioxamine not cobalt has any influence on the NADH stimulated O2-
      generation. Incubation with cobalt or with desferrioxamine, however, leads to a
      decrease of the intracellular H2O2 level as revealed by the dihydrorhodamine 123
      technique, perhaps causing the well-known enhanced erythropoietin production. The
      cobalt-induced H2O2 decrease seems to be caused by an increased activity of the
      glutathion peroxidase that is also induced under hypoxia. Desferrioxamine,
      however, leads to an apparent H2O2 decrease only because it seems to inhibit the
      iron catalyzed reaction of H2O2 with dihydrorhodamine 123, hinting at the
      occurrence of the Fenton reaction in HepG2 cells. Therefore, it must be
      determined whether or not degradation products of H2O2 by the Fenton reaction
      suppress erythropoietin production under normoxia.

PMID- 9027729
TI  - Effects of antioxidant vitamins on renal and hepatic erythropoietin production.
AB  - An important role in O2 sensing has been assigned to microsomal and membrane
      bound b-type cytochromes which generate regulatory reactive O2 species (ROS).
      Recently, ROS have been shown to suppress the in vitro synthesis of
      erythropoietin (Epo). We investigated the potential of the antioxidant vitamins
      A, E and C to enhance renal and hepatic Epo production. Renal effects were
      studied in isolated serum-free perfused rat kidneys. In control experiments
      without antioxidant vitamins, Epo secretion amounted to 441 +/- 23 mU/g kidney
      (mean +/- SEM, N = 5) during the three hour period of hypoxic perfusion (arterial
      pO2 35 mm Hg). Epo secretion significantly increased to 674 +/- 92 mU/g kidney (N
      = 7) when vitamins A (0.5 microgram/ml), E (0.5 microgram/ml) and C (10
      micrograms/ml) in combination were added to the perfusion medium. The effects of
      the single vitamins were studied in Epo-producing hepatoma cell cultures (lines
      HepG2 and Hep3B). Vitamin A induced a dose-dependent increase (half-maximal
      stimulation at 0.2 microgram/ml) in the production of immunoreactive Epo during
      24 hours of incubation (such as 680 +/- 51 U Epo/g cell protein in HepG2 cultures
      with 3 micrograms/ml retinol acetate compared to 261 +/- 15 U/g in untreated
      controls; N = 4). In contrast, vitamin E (tested from 0.05 to 500 micrograms/ml)
      and vitamin C (tested from 2 to 200 micrograms/ml) did not increase Epo
      production in hepatoma cell cultures. Thus, while vitamins E and C may have the
      potential to protect cells from oxidative damage, vitamin A exerts a specific
      stimulation of Epo production. Preliminary evidence suggests that this effect of
      vitamin A involves increased mRNA levels of hypoxia-inducible factor 1 alpha (HIF
      1 alpha).

PMID- 9027730
TI  - Oxygen-dependent regulation of erythropoietin gene expression in rat hepatocytes.
AB  - The essential role of the glycoprotein hormone erythropoietin (Epo) in the
      control of red blood cell production is well established. Synthesis of Epo is
      induced in response to low oxygen (hypoxia). In response to stimulation,
      increases in serum Epo levels are paralleled by changes in the abundance of Epo
      mRNA. These changes indicate that the level of Epo mRNA is the major determinant
      of hormone production rate [1-3]. Studies of the organ distribution of Epo mRNA
      [4, 5] have confirmed the results of organ ablation studies, which demonstrated
      that in adults the kidney is the major organ responsible for the Epo production,
      but the liver is capable of Epo production as well [6, 7]. More sensitive
      detection methods of Epo mRNA have demonstrated small quantities in testis,
      brain, lung, and spleen of rodents [3, 8].

PMID- 9027731
TI  - Regulation of hypoxic gene expression in yeast.
AB  - Baker's yeast, Saccharomyces cerevisiae, can adapt to growth under severe oxygen
      limitation. Two regulatory systems are described here that control this
      adaptation. The first involves a heme-dependent repression mechanism. Cells sense
      hypoxia through the inability to maintain oxygen-dependent heme biosynthesis.
      Under aerobic conditions, heme accumulates and serves as an effector for the
      transcriptional activator Hap1. The heme-Hap1 complex activates transcription of
      the ROX1 gene that encodes a repressor of one set of hypoxic genes. Under hypoxic
      conditions, heme levels fall, and a heme-deficient Hap1 complex represses ROX1
      expression. As a consequence, the hypoxic genes are derepressed. The second
      regulatory system activates gene expression in response to a variety of stress
      conditions, including oxygen limitation. Oxygen sensing in this system is heme
      independent. The same DNA sequence mediates transcriptional activation of each
      stress signal.

PMID- 9027732
TI  - Oxygen regulated gene expression: erythropoietin as a model system.

PMID- 9027733
TI  - Regulation of gene expression for tyrosine hydroxylase in oxygen sensitive cells
      by hypoxia.
AB  - Carotid body type I cells and the O2 sensitive pheochromocytoma (PC12) cells
      release dopamine during hypoxia. Reduced O2 tension causes inhibition of an
      outward rectifying the O2-sensitive potassium (K) channel in the O2-sensitive
      pheochromocytoma (PC12) cell line, which leads to membrane depolarization and
      increased intracellular free Ca2+. We found that removal of Ca2+ from the
      extracellular milieu, inhibition of voltage-dependent Ca2+ channels, and
      chelation of intracellular Ca2+ prevents full activation of the TH gene
      expression during hypoxia. These findings suggest that membrane depolarization
      and regulation of intracellular free Ca2+ are critical signal transduction events
      that regulate expression of the TH gene in PC12 cells during hypoxia. Gene
      expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in the
      biosynthesis of dopamine, is stimulated by reduced O2 tension in both type I
      cells and PC12 cells. The increase in TH gene expression in PC12 cells during
      hypoxia is due to increases in both the rate of transcription and mRNA stability.
      Analysis of reporter-gene constructs revealed that increased transcription of the
      TH gene during hypoxia is regulated by a region of the proximal promoter that
      extends from -284 to -150 bases, relative to the transcription start site. This
      region of the gene contains a number of cis-acting regulatory elements including
      AP1, AP2 and hypoxia-inducible factor (HIF-1). Competition assays revealed that
      hypoxia-induced binding occurs at both the AP1 and HIF-1 sites. Results from
      super-shift and shift Western assays showed that a heterodimer consisting of c
      Fos and JunB binds to the AP1 site during hypoxia. Mutagenesis experiments
      revealed that the AP1 site is required for increased transcription of the TH gene
      during hypoxia. We also found that the genes that encode the c-Fos and JunB
      transcription factor proteins are regulated by reduced O2 tension.

PMID- 9027734
TI  - Regulation of tyrosine hydroxylase gene expression during hypoxia: role of Ca2+
      and PKC.
AB  - Gene expression for tyrosine hydroxylase (TH), the rate-limiting enzyme in
      catecholamine biosynthesis, is regulated by reductions in oxygen tension
      (hypoxia). Hypoxia-induced regulation of the TH gene is due to the binding of
      specific transcription factors to specific sites on the 5' flanking region of the
      gene. The purpose of this study was to identify the second messenger system(s)
      responsible for regulation of the TH gene during hypoxia. Fura-2 fluorescence
      imaging of rat pheochromocytoma (PC12) cells, an O2-sensitive cell line, revealed
      that there is an increase in cytosolic calcium (Ca2+) associated with exposure to
      hypoxia. Based on the evidence that the transcription factors that bind to the TH
      promoter during hypoxia can also be induced by elevations in cytosolic Ca2+, the
      role of Ca2+ in the hypoxic regulation of the TH gene was explored. To assay the
      effect of hypoxia on TH gene expression, Northern blot analyses of total RNA were
      performed on PC12 cells exposed to hypoxia in the presence or absence of specific
      inhibitors. The addition of the L-type calcium channel blockers nifedipine or
      verapamil caused partial inhibition of the hypoxia-induced increase in TH mRNA.
      The increase in cytosolic Ca2+ during hypoxia was also only partially inhibited
      by addition of nifedipine. Importantly, chelation of extracellular Ca2+
      completely inhibited the increase in TH mRNA by hypoxia. Pretreatment of PC12
      cells with BAPTA/AM, an intracellular Ca2+ chelator, inhibited the hypoxic
      induction of TH gene expression in a dose-dependent manner. Addition of
      chelerythrine chloride (CHL), a protein kinase C inhibitor, to the media before
      exposure to hypoxia also resulted in an inhibition of TH induction by hypoxia.
      These results suggest that hypoxia regulates TH gene expression by a mechanism
      that is dependent on influx of calcium from the extracellular stores, partially
      but not exclusively through the L-type calcium channels. These results further
      suggest that a member of the PKC family is essential for this regulation.

PMID- 9027735
TI  - Diminution of the O2 responsiveness of the glucagon-dependent activation of the
      phosphoenolpyruvate carboxykinase gene in rat hepatocytes by long-term culture at
      venous PO2.
AB  - The glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK)
      gene within two hours is modulated by O2 in rat hepatocytes. It was the aim of
      the present study to test if this short-term modulation by O2 of the glucagon
      induction might be influenced by long-term culture of hepatocytes for 24 hours
      under different O2 tensions prior to glucagon induction. Cells were precultured
      for 24 hours at arterial O2 (16% O2) or venous O2 (8% O2), then induced within
      two to four hours with 1 nM glucagon each at arterial or venous O2. In arterial
      O2 precultured cells PCK mRNA and activity were induced to 100% at arterial O2
      and to about 60% at venous O2. In venous O2 precultured cells PCK mRNA and
      activity were induced only to about 70% at arterial O2 and to about 60% at venous
      O2. Transfected PCK promoter (-2500)-CAT constructs were activated by glucagon
      with the same long-term modulatory effects of oxygen as the endogenous PCK gene.
      Gel mobility shift assays with nuclear extracts prepared from hepatocytes and a
      PCK promoter fragment ranging from -149 to -42 bp revealed one complex with a
      higher DNA binding activity when extracts of cells precultured for 24 hours under
      venous O2 as compared to arterial O2 were used. Therefore, the short-term
      modulation by O2 of PCK gene activation by glucagon was widely lost during
      preculture at low O2. This diminution of O2 sensitivity of PCK induction may be
      due to a nuclear protein or proteins which are induced by perivenous O2 tensions
      and bind to the PCK promoter.

PMID- 9027736
TI  - Erythropoietin gene regulation depends on heme-dependent oxygen sensing and
      assembly of interacting transcription factors.
AB  - Studies on erythropoietin (Epo) gene expression have been useful in investigating
      the mechanism by which cells and tissues sense hypoxia. Both in vivo and in Hep3B
      cells. Epo production is induced not only by hypoxia but also by certain
      transition metal (cobalt and nickel) and by iron chelation. When Hep3B cells were
      incubated in an iron deficient medium, Epo mRNA expression was enhanced fourfold
      compared to Hep3B cells in iron enriched medium. Epo induction by cobalt was
      inversely related to iron concentration in the medium, indicating competition
      between the two metals. Under hyperbaric oxygen, cobalt induction of
      erythropoietin mRNA was modestly suppressed while nickel induction was markedly
      enhanced. These recent observations support the proposal that the oxygen sensor
      is a heme protein in which cobalt and nickel can substitute for iron in the
      porphyrin ring. The up-regulation of Epo gene transcription by hypoxia depends on
      at least two known DNA binding transcription factors, HIF-1 and HNF-4, which bind
      to cognate response elements in a critical approximately 50 bp 3' enhancer.
      Hypoxia induces HIF-1 binding. HNF-4, an orphan nuclear receptor constitutively
      expressed in kidney and liver, binds downstream of HIF-1 and cooperates with HIF
      1, contributing importantly to high level and perhaps tissue specific expression.
      The C-terminal activation domain of HNF-4 binds to the beta subunit of HIF-1. The
      C-terminal portion of the alpha subunit of HIF-1 binds specifically to p300, a
      general transcriptional activator. Hypoxic induction of the endogenous Epo gene
      in Hep3B cells as well as an Epo-reporter gene was fully inhibited by E1A, an
      adenovirus protein that binds to and inactivates p300, but only slightly by a
      mutant E1A that fails to bind to p300. Moreover, overexpression of p300 enhanced
      hypoxic induction. Thus, it is likely that in hypoxic cells, p300 or a related
      family member plays a critical role in forming a macromolecular assembly with HIF
      1 and HNF-4, enabling transduction from the Epo 3' enhancer to the apparatus on
      the promoter responsible for the initiation of transcription.

PMID- 9027737
TI  - Structural and functional analysis of hypoxia-inducible factor 1.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a basic helix-loop-helix protein that
      activates transcription of hypoxia-inducible genes, including those encoding:
      erythropoietin, vascular endothelial growth factor, heme oxygenase-1, inducible
      nitric oxide synthase, and the glycolytic enzymes aldolase A, enolase 1, lactate
      dehydrogenase A, phosphofructokinase I, and phosphoglycerate kinase 1. Hypoxia
      response elements from these genes consist of a HIF-1 binding site (that contains
      the core sequence 5'-CGTG-3') as well as additional DNA sequences that are
      required for function, which in some elements include a second HIF-1 binding
      site. HIF-1 is a heterodimer. The HIF-1 alpha subunit is unique to HIF-1, whereas
      HIF-1 beta (ARNT) can dimerize with other bHLH-PAS proteins. Structural analysis
      of HIF-1 alpha revealed that dimerization with HIF-1 beta (ARNT) requires the HLH
      and PAS domains, DNA binding is mediated by the basic domain, and that HIF-1
      alpha contains a carboxyl-terminal transactivation domain. Co-transfection of HIF
      1 alpha and HIF-1 beta (ARNT) expression vectors and a reporter gene containing a
      wild-type hypoxia response element resulted in increased transcription in non
      hypoxic cells and a superinduction of transcription in hypoxic cells, whereas HIF
      1 expression vectors had no effect on the transcription of reporter genes
      containing a mutation in the HIF-1 binding site. HIF-1 alpha and HIF-1 beta
      (ARNT) protein levels were induced by hypoxia in all primary and transformed cell
      lines examined. In HeLa cells, the levels of HIF-1 alpha and HIF-1 beta protein
      and HIF-1 DNA-binding activity increased exponentially as cellular oxygen tension
      decreased, with maximum values at 0.5% oxygen and half-maximal values at 1.5 to
      2% oxygen. HIF-1 alpha and HIF-1 beta (ARNT) mRNAs were detected in all human,
      mouse, and rat organs assayed and mRNA expression was modestly induced in rodents
      subjected to hypoxia. HIF-1 alpha protein levels were induced in vivo when
      animals were subjected to anemia or hypoxia. The HIF1A gene was mapped to human
      chromosome 14q21-q24 and mouse chromosome 12.

PMID- 9027738
TI  - Complex role of protein phosphorylation in gene activation by hypoxia.

PMID- 9027739
TI  - Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level.
AB  - The hypoxia-inducible factor-1 (HIF-1) is involved in the induction of oxygen
      regulated genes such as erythropoietin and vascular endothelial growth factor
      (VEGF). HIF-1 is a heterodimeric transcription factor consisting of an alpha and
      a beta subunit. The question of how HIF-1 itself is regulated remains to be
      elucidated. Studies performed in human Hep3B hepatoma cells suggested that the
      prevalent mode of HIF-1 action is an increase in HIF-1 alpha steady-state mRNA
      and protein levels after hypoxic exposure. In contrast to the reported very low
      basal HIF-1 alpha mRNA levels, however, we detected HIF-1 alpha mRNA in several
      cell lines cultured under normoxic conditions, although no HIF-1 DNA binding
      activity was observed. Following hypoxic induction, VEGF mRNA levels and HIF-1
      DNA binding activity increased, but HIF-1 alpha mRNA levels remained largely
      unchanged. One possible explanation for this discrepancy might be that HIF-1 DNA
      binding activity does not follow HIF-1 alpha mRNA kinetics. We therefore
      incubated HeLaS3 cells in tonometers for 7.5 minutes up to four hours at either
      20% O2 or 0.5% O2. Although there was some variation in HIF-1 alpha mRNA levels,
      we did not find significant changes over this time frame, suggesting that HIF-1
      alpha is not transcriptionally regulated.

PMID- 9027740
TI  - The hypoxia-inducible factor-1 DNA recognition site is cAMP-responsive.
AB  - The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding
      activity that specifically recognizes an 8 bp hypoxia response element (HRE)
      known to be essential for oxygen-regulated erythropoietin gene expression. In
      electrophoretic mobility shift assays (EMSAs) HIF-1 DNA binding activity is only
      detectable in nuclear extracts of cells cultivated in a low oxygen atmosphere. In
      addition to HIF-1, a constitutive DNA binding activity also specifically binds
      the HIF-1 probe. Based on EMSAs using competitor oligonucleotides, specific
      antibodies and recombinant proteins, we previously reported that the constitutive
      HRE binding factor is composed of ATF-1 and CREB-1. Here we show that this site
      is functionally responsive to the cAMP agonist 8Br-cAMP in a dose-dependent
      manner under hypoxic but not under normoxic conditions. These results were
      confirmed by using the protein kinase A (PKA) activator Sp-cAMPS and the PKA
      inhibitor Rp-cAMPS: while Sp-cAMPS was synergistic with hypoxia on the HIF-1 DNA
      recognition site, the Rp-cAMPS isomer showed no effect. Our findings suggest that
      the PKA-signaling pathway is enhancing oxygen-dependent gene expression via the
      HRE.

PMID- 9027741
TI  - Oxygen- and dioxin-regulated gene expression in mouse hepatoma cells.
AB  - The discovery that the oxygen-regulated transcription factor HIF-1 alpha and the
      dioxin receptor AhR share the common heterodimerization partner ARNT (HIF-1 beta)
      raised the question whether a cross-talk between oxygen and dioxin signal
      transduction pathways exists. To answer this question we investigated an ARNT
      deficient mutant cell line (Hepa1C4), which has lost its capability of responding
      to dioxin. The results demonstrate that the presence of ARNT is indispensable for
      hypoxia-inducible HIF-1 DNA binding as well as for oxygen-regulated reporter gene
      activity mediated by the EPO 3' hypoxia response element (HRE). Hypoxic induction
      of the vascular endothelial growth factor (VEGF) gene, however, was only
      partially abrogated in Hepa1C4 cells, suggesting that HIF-1-independent oxygen
      signaling pathways might exist. We further studied HIF-1 and AhR/ARNT DNA binding
      activity as well as the regulation of oxygen- and xenobiotic-responsive genes by
      treating mouse Hepa1 hepatoma cells with hypoxia and/or the dioxin analogue ICZ.
      Hypoxia-inducible VEGF expression was found to be independent of ICZ-treatment,
      whereas ICZ-inducible cytochrome P-450IA1 expression was slightly reduced by
      hypoxic treatment of the cells. Interestingly, the enhancer function of a
      xenobiotic response element (XRE) linked to a reporter gene was induced by
      hypoxia, but expression of a HRE-containing reporter gene was not affected by ICZ
      treatment.

PMID- 9027743
TI  - Interaction of erythropoietin RNA binding protein with erythropoietin RNA
      requires an association with heat shock protein 70.
AB  - Synthesis of erythropoietin (Epo), the glycoprotein hormone that regulates red
      blood cell formation, is induced in response to low oxygen stress (hypoxia), and
      is regulated at both transcriptional and post-transcriptional levels. We have
      previously described an Epo RNA binding protein (ERBP) which specifically binds
      to the 3'-untranslated region of Epo mRNA and is likely involved in the
      regulation of Epo mRNA stability. Since heat shock proteins (hsps) are induced in
      response to a variety of stresses, including hypoxia, we tested the possibility
      that hsps are involved in ERBP-Epo RNA complex formation. When human anti-hsp70
      antibody was added to ERBP-containing human hepatoma cell (Hep3B) lysates, the
      ERBP-Epo RNA complex was inhibited in an electrophoretic mobility band shift
      assay. In addition, the anti-hsp70 antibody-inhibited complex could be rescued if
      lysates were pretreated with purified inducible hsp70, but not with bovine serum
      albumin (BSA). In vivo studies using quercetin to inhibit hsp70 induction support
      the notion that hsp70 is involved in ERBP-Epo RNA complex formation. Taken
      together, these findings suggest involvement of hsp70 in ERBP-Epo mRNA complex
      formation, and our model suggests a novel role for hsps in the regulation of EPO
      mRNA stability.

PMID- 9027744
TI  - Post-transcriptional regulation of tyrosine hydroxylase gene expression by oxygen
      in PC12 cells.
AB  - Reduced oxygen tension (hypoxia) leads to increased stability of mRNA for
      tyrosine hydroxylase (TH), the rate limiting enzyme in biosynthesis of
      catecholamine neurotransmitters. Hypoxia increases the half life of TH mRNA from
      10 to 30 hours. The increased stability of TH mRNA during hypoxia results from
      fast enhanced binding of a cytoplasmic protein (hypoxia inducible protein, HIP)
      to a pyrimidine-rich sequence within the 3' untranslated region (3'UTR) of TH
      mRNA. This novel cis-element is referred to as hypoxia-inducible protein binding
      site (HIPBS) and is located between bases 1551 and 1578 of the 3' UTR of TH mRNA.
      We identified that the (U/C)(C/U)CCCU motif within the HIPBS represents the
      optimum protein-binding site. Mutations within this region that abolish protein
      binding prevent also regulation of TH mRNA stability during hypoxia. UV
      crosslinking and SDS-PAGE analysis of the HIPBS-protein complexes showed the
      presence of a major 50 kDa complex. The formation of the complex was augmented
      when protein extracts were obtained from PC12 cells exposed to 5% O2.
      Importantly, formation of the 50 kDa complex was also increased when protein
      extracts were obtained from carotid bodies or superior cervical ganglia from rats
      exposed to 10% hypoxia for twenty-four hours.

PMID- 9027745
TI  - Hyperkalemic hyperchloremic metabolic acidosis: pathophysiologic insights.

PMID- 9027742
TI  - Regulation of vascular endothelial growth factor by hypoxia and its modulation by
      the von Hippel-Lindau tumor suppressor gene.
AB  - The regulation of VEGF production is mediated by both transcriptional and post
      transcriptional mechanisms. A schematic model of elements involved in hypoxic
      regulation of VEGF is shown in Figure 1.

PMID- 9027746
TI  - Hemoglobin catabolism and iron utilization by malaria parasites.
AB  - Erythrocytic malaria parasites transport large quantities of erythrocyte
      cytoplasm to an acidic food vacuole, where hemoglobin is degraded. Globin is
      hydrolysed to free amino acids, which are subsequently incorporated into parasite
      proteins. Potentially toxic heme moieties are polymerized to hemozoin and also
      probably provide necessary parasite iron. Our understanding of the precise
      mechanisms of hemoglobin processing is incomplete. However, it is clear that
      hemoglobin catabolism and related events in the malarial food vacuole are the
      likely targets of both important antimalarial drugs and of promising new
      compounds. Thus, a more precise characterization of the metabolism of hemoglobin
      and iron by malaria parasites should expedite the development of new modes of
      antimalarial chemotherapy.

PMID- 9027747
TI  - DNA markers define two major phylogenetic lineages of Trypanosoma cruzi.
AB  - Parasitic protozoa within the taxon Trypanosoma cruzi are considered to be
      derived from multiple clonal lineages, and show broad genetic diversity as a
      result of propagation with little or no genetic exchange. We have analyzed a wide
      sample of T. cruzi isolates from vertebrate and invertebrate hosts by PCR
      amplification of a ribosomal RNA gene sequence, a mini-exon gene sequence and
      random amplified polymorphic DNA (RAPD). Amplification of the distinct rDNA and
      mini-exon gene sequences indicated a dimorphism within both of the tandemly
      repeated genes: 125 or 110 bp products for rDNA and 300 or 350 bp products for
      the mini-exon. Within individual isolates, one of three associations was
      observed: the 125 bp rDNA product with the 300 bp mini-exon product (defined as
      group 1), the 110 bp rDNA product with the 350 bp mini-exon product (defined as
      group 2) and the presence of both rDNA amplification products with the mini-exon
      group 1 product (group 1/2). The RAPD analysis showed variability between
      individual isolates, however, tree analysis clearly indicated the presence of two
      major branches. Interestingly, the rDNA/mini-exon group 2 isolates correlated
      precisely with one branch of the RAPD-derived tree; group 1 and group 1/2
      isolates correlated with the other branch. Our studies show a clear division of
      T. cruzi into two major lineages presenting a high phylogenetic divergence.
      Hypotheses are discussed to explain the origin of the two lineages as well as
      isolates that are hybrid for group 1 and 2 rDNA markers.

PMID- 9027748
TI  - Cloning, sequencing and expression of a cDNA encoding an antigen from the
      Myxosporean parasite causing the proliferative kidney disease of salmonid fish.
AB  - A pool of monoclonal antibodies (MAbs) raised against the unknown organism
      causing the proliferative kidney disease of salmonid fish (PKX) has been used to
      screen a cDNA expression library constructed from poly (A+) RNA extracted from
      PKX infected kidney. Four immunopositive lambda ZapII recombinant phages were
      selected. Sequencing of the cDNAs revealed identical 3' ends. The longest cDNA
      clone (2652 nucleotides) had an open reading frame (ORF) of 872 amino acids and
      encoded a protein with a predicted size of 101 kDa (PKX101). Sequence analysis of
      PKX101 revealed two leucine zipper motifs, a putative transmembrane region and a
      microbody targeting signal at its C-terminal end. Three cDNA fragments were
      subcloned in pET-14b expression vector and the ORF verified by an in vitro
      transcription/translation procedure. Recombinant clones were expressed in
      Escherichia coli and the antigenicity of fusion proteins was studied by Western
      blotting using monoclonal antibodies directed against PKX cells and a pool of
      serum from preimmune or PKX-infected rainbow trout. Western blotting of enriched
      PKX cell antigen probed with one MAb or with sera from infected trout revealed a
      single protein with relative mobility of 13 kDa (PKX13). This discrepancy between
      PKX101 and PKX13 observed in Western blot suggests post-translational
      modifications of the full-length PKX antigen.

PMID- 9027749
TI  - The SLA RNA gene of Trypanosoma brucei is organized in a tandem array which
      encodes several small RNAs.
AB  - We have recently identified the Spliced Leader Associated RNA (SLA RNA) which is
      implicated in pre-messenger RNA splicing in Trypanosoma brucei by virtue of its
      interaction with the 5' splice site of the trans spliced spliced leader RNA (SL
      RNA) in vivo. Southern analyses reveal that the SLA RNA gene is found in a tandem
      array of 10-11 copies per haploid genome in T. brucei. Each repeat unit in the
      array encodes three additional small RNAs of unknown function. RNA polymerase
      inhibition studies are consistent with transcription of all four genes by the
      same polymerase, but do not clearly differentiate between RNA polymerases II and
      III. The SLA RNA has homologs in other kinetoplastid protozoa and we have
      determined the sequence from two additional species. Trypanosoma cruzi and
      Crithidia fasciculata. Features of both secondary structure and sequence are
      conserved in these organisms. One conserved element, 5'-UGUAGUG-3', has the
      potential to base-pair to the SL RNA upstream of the 5' splice site. This
      potential interaction is consistent with the sites of SL RNA to SLA RNA psoralen
      cross-linking in vivo [1].

PMID- 9027750
TI  - Detection, purification and partial characterization of beta-amylase from
      trophozoites of Entamoeba invadens.
AB  - Trophozoites of Entamoeba invadens were able to ingest glucopolysaccharides and
      metabolize them. An activity capable of degrading these substrates was purified
      to apparent homogeneity. The enzyme was identified as beta-amylase (alpha-1,4-D
      glucan maltohydrolase EC 3.2.1.2): It was active against glycogen, amylose and
      amylopectin in a ratio of 100:198:133 and was also able to attack linear alpha
      1,4-glucooligosaccharides with more than three glucose moieties. All degradation
      experiments yielded maltose as reaction product, and no free glucose could be
      detected. While amylose was completely degraded, amylolysis of glycogen and
      amylopectin yielded limit dextrins besides maltose. The enzyme was completely
      inactive against cyclohexaamylose, cycloheptaamylose and pullulan, indicating its
      lack of endo-glucosidase specificity. Hydrolysis of 4-nitrophenyl-maltoheptaoside
      resulted in the successive removal of maltose units from the non-reducing end
      yielding 4-nitrophenyl-maltopentaoside, -trioside and -glucoside. No 4
      nitrophenyl-glycosides with even numbered glucose moieties were formed from this
      substrate. The enzyme exhibited a relative molecular mass of M(r) = 45,000 +/- 5%
      by gel filtration and sodium dodecyl sulfate (SDS) gel electrophoresis and the N
      terminal sequence 1 VEVNVMLPL 9. Optimal hydrolysis was observed at pH 5.5 and a
      temperature of 42 degrees C. On the basis of inhibition by mercury ions and p
      chloro-mercurybenzoate and abrogation of this effect by thiol reagents beta
      amylase was identified as sulfhydryl-enzyme.

PMID- 9027751
TI  - Formation of hydroxyeicosatetraenoic acids from hemozoin-catalyzed oxidation of
      arachidonic acid.
AB  - Hemozoin, a heme byproduct of hemoglobin digestion by malaria parasites, is
      released into the blood stream of the host upon lysing of infected erythrocytes.
      Since heme-compounds are potent catalysts of lipid peroxidation, we evaluated the
      catalytic ability of Plasmodium falciparum-derived hemozoin to oxidize
      arachidonic acid to hydroxyeicosatetraenoic acids (HETEs). Hemozoin, beta
      hematin, and hematin all catalyzed the formation of 15-, 12- and 5-HETE as major
      products. Although there were no significant differences in total amounts of
      HETEs generated by hemozoin relative to hematin or beta-hematin, there were
      significant differences in the proportions of certain isomers. 15-HETE was the
      predominant isomer generated by hemozoin catalysis while 5-HETE was the major
      product formed by hematin catalysis. Since HETEs are important vasoactive
      mediators, the non-enzymatic oxidation of arachidonic acid by hemozoin catalysis
      may contribute to some of the pathophysiology associated with severe and cerebral
      malaria.

PMID- 9027752
TI  - Characterization of native falcipain, an enzyme involved in Plasmodium falciparum
      hemoglobin degradation.
AB  - In Plasmodium falciparum, a cysteine protease known as falcipain has been
      implicated in the essential metabolic process of hemoglobin degradation. Parallel
      lines of investigation, using native or recombinant enzyme, have led to differing
      conclusions about the specificity and role of this protease. We have now
      determined that (1) Native falcipain does not cleave hemoglobin unless this
      substrate has first been denatured by reducing agents, acid-acetone treatment or
      plasmepsin action. (2) Reducing agents such as glutathione cannot denature
      hemoglobin in the presence of catalase, which is accumulated in the digestive
      vacuole. (3) The purified native enzyme has kinetics similar to those obtained
      with trophozoite extract, but substantially different from those of recombinant
      enzyme. (4) Although there are numerous cysteine protease genes in the P.
      falciparum genome, the falcipain gene is the only one whose transcript can be
      detected in the early intraerythrocytic parasites. We conclude that falcipain
      likely works by degrading hemoglobin fragments after initial aspartic protease
      attack has denatured the substrate. We propose that falcipain inhibitors block
      the initial steps of degradation indirectly by promoting vacuolar accumulation of
      osmotically active hemoglobin peptides.

PMID- 9027753
TI  - The MIC1 microneme protein of Toxoplasma gondii contains a duplicated receptor
      like domain and binds to host cell surface.
AB  - The cDNA encoding the Toxoplasma gondii microneme protein MIC1 and the
      corresponding gene have been cloned and sequenced. The MIC1 gene contains three
      introns. The cDNA encodes a 456 amino acid (aa) sequence, with a typical signal
      sequence and no other trans-membrane domain. The protein contains a tandemly
      duplicated domain with conservation of cysteines and presents distant homology
      with the Plasmodium sp. microneme protein TRAP-SSP2. The MIC1 protein from
      tachyzoite lysates and a PMAL recombinant expressing the N-terminal duplicated
      domain of the protein bound to the surface of putative host cells, suggesting a
      possible involvement of MIC1 in host cell binding/recognition.

PMID- 9027754
TI  - A thioredoxin reductase-class of disulphide reductase in the protozoan parasite
      Giardia duodenalis.
AB  - We describe the purification and characterisation of a thioredoxin reductase-like
      disulphide reductase from the ancient protozoan parasite, Giardia duodenalis.
      This dimeric flavoprotein contains 1 mol FAD per subunit and had an apparent
      subunit molecular mass of 35 kDa. The purified enzyme catalysed the NADPH
      dependent (Km = 8 microM) reduction of 5,5'-dithio-bis(2-nitrobenzoic acid) to
      thionitrobenzoate and was unable to utilise NADH as an electron donor. The
      sulphydryl-active compounds, N-ethylmaleimide, sodium arsenite and Zn2+ ions,
      strongly inhibited the enzyme suggesting that a thiol component forms part of the
      active site. Purified enzyme was able to utilise a variety of substrates,
      including cystine and oxidised glutathione, which suggests that it is a broad
      range disulphide reductase, probably accounting for the majority of thiol cycling
      activity in this organism. While the G. duodenalis enzyme does not require an
      intermediate electron transport protein, analogous to thioredoxin, for activity,
      we have identified a candidate carrier protein which enhances DTNB turnover six
      fold, therefore implying that Giardia contains a thioredoxin-like system.
      Physical, enzymatic and spectral properties of the G. duodenalis disulphide
      reductase are also consistent with it being a member of the thioredoxin reductase
      class of disulphide reductases. Furthermore, the internal amino acid sequence of
      a tryptic peptide generated from the purified protein was highly homologous with
      thioredoxin reductases from other sources. This is the first report of a
      disulphide reductase to be purified from the anaerobic protozoa and explains the
      so called "glutathione-induced thiol-reductase activity' previously observed in
      G. duodenalis.

PMID- 9027755
TI  - Iron-ascorbate cleavable malic enzyme from hydrogenosomes of Trichomonas
      vaginalis: purification and characterization.
AB  - Two isoforms of NAD(P)(+)-dependent malic enzyme (EC 1.1.1.39) were isolated from
      hydrogenosomes of Trichomonas vaginalis. A positively charged isoform at pH 7 was
      obtained in a single purification step using cation-exchange chromatography. The
      second isoform, negatively charged at pH 7.5, was partially purified using a
      combination of anion-exchange and affinity chromatography. Both isoforms
      displayed similar physical and kinetic properties. Molecular weight determination
      of the native enzyme suggested a homotetrameric arrangement of the 60 kDa
      subunits. The enzyme utilized NAD+ (Km, 6-6.3 microM) preferentially to NADP+
      (Km, 125-145 microM). The NAD(+)-dependent activity showed a broad pH optimum
      with maximum under alkaline conditions (pH 9) likely to be present inside
      hydrogenosomes. Immunocytochemical studies using a polyclonal rabbit antibody
      raised against purified T. vaginalis malic enzyme proved hydrogenosomal
      localization of the enzyme. Subfractionation of hydrogenosomes suggested an
      association of the malic enzyme with the hydrogenosomal membranes. The 60 kDa
      malic enzyme subunit was highly sensitive to non-enzymatic cleavage by an iron
      ascorbate system resulting in two enzymatically inactive fragments of about 31
      kDa. Microsequencing of the fragments revealed that the 60 kDa subunit was
      cleaved at the metal-binding site between Asp279-Ile280. The enzyme inactivation
      was inhibited by an excess of manganese. Iron-dependent posttranslational
      modification might contribute to the regulation of malic enzyme activity in vivo.

PMID- 9027756
TI  - The 5S ribosomal RNA intergenic region of parasitic nematodes: variation in size
      and presence of SL1 RNA.

PMID- 9027757
TI  - Single copy Babesia microti hsp70.

PMID- 9027758
TI  - An unexpected 5' untranslated intron in the P. falciparum genes for histidine
      rich proteins II and III.

PMID- 9027759
TI  - Differential glycosylation of epitope-tagged glycoprotein Gp72 during the
      Trypanosoma cruzi life cycle.

PMID- 9027760
TI  - Stable episomal transfection and gene expression in Entamoeba dispar.

PMID- 9027761
TI  - Endothelial vasoregulation and mechanosensitive ion channels in hypertension.

PMID- 9027762
TI  - Amylin--its role in the kidney.

PMID- 9027763
TI  - Phosphatonin--a new phosphaturetic hormone? (lessons from tumour-induced
      osteomalacia and X-linked hypophosphataemia)

PMID- 9027764
TI  - Protein degradation by proteasomes: molecular mechanisms of muscle catabolism.

PMID- 9027765
TI  - How important is vitamin D deficiency in uraemia?

PMID- 9027766
TI  - Should hyperlipidaemia in dialysis patients be treated?

PMID- 9027767
TI  - Metabolic abnormalities in renal transplant recipients. Risk factors and
      predictors of chronic graft dysfunction?
AB  - In summary, abnormalities in lipid and carbohydrate metabolism, including
      features of the metabolic risk factor syndrome, are frequently present in
      patients both before and after renal transplantation. Risk factors of
      atherosclerosis may not only contribute to increased cardiovascular morbidity and
      mortality in this patient population, but can also be assumed to contribute to
      the development and progression of CVR and chronic graft dysfunction. For
      preventing both early graft losses and the development of graft damage leading to
      late graft dysfunction and graft loss, it appears to be essential to identify
      patients at risk early, prior to transplantation. Intervention aiming to reduce
      overweight, diet and exercise may be of benefit. The role of omega-3 unsaturated
      fatty acid supplementation remains controversial. Pharmacological intervention by
      antioxidants or agents to reduce lipids and/or decrease PAI-1 synthesis may prove
      to be beneficial. Early identification of patients at risk and intervention in
      due time may improve the results of renal transplantation.

PMID- 9027768
TI  - Calcium channel blockers: what they can and what they can't do.

PMID- 9027769
TI  - Audit of quality of hospital haemodialysis in Scotland. The Scottish Renal
      Registry.

PMID- 9027770
TI  - Medical and psychosocial rehabilitation of young adults receiving renal
      replacement therapy since childhood: a single-centre experience.

PMID- 9027771
TI  - Membrane biocompatibility in the treatment of acute renal failure: what is the
      evidence in 1996?

PMID- 9027772
TI  - Myofibroblasts and the progression of diabetic nephropathy.
AB  - BACKGROUND: The cellular mediators of progressive renal fibrosis in diabetic
      nephropathy remain unknown. Myofibroblasts have been implicated in the
      pathogenesis of experimental and clinical renal fibrosis. Their role in the
      progression of diabetic nephropathy is the subject of this study. SUBJECTS AND
      METHODS: We have studied by immuno-histochemistry the expression of cytoskeletal
      proteins associated with the activation of myofibroblasts; alpha-smooth-muscle
      actin (alpha-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients
      with diabetic nephropathy (5 patients had a superimposed glomerulonephritis).
      Comparisons were made with normal tissue from three kidneys removed for renal
      cell carcinoma. Correlations were studied between clinical and biochemical
      parameters with the expression of renal cytoskeletal proteins. RESULTS: In normal
      kidneys, cells expressing alpha-SMA were confined to the vascular media and
      adventitia while immunoreactive Vi was detected in glomerular epithelial cells.
      In diabetic kidneys, cells expressing alpha-SMA were detected primarily in the
      renal interstitium and to a lesser extent in some glomeruli in association with
      mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying
      diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was
      noted in atrophic diabetic tubules and to a lesser extent in the interstitium.
      Desmin was not detected in either normal or diabetic kidneys. Close correlations
      were observed between the expression of renal cytoskeletal proteins and the
      progression of renal insufficiency. Interstitial alpha-SMA proved to be a
      predictor of progressive diabetic nephropathy (R2 for 1/serum Cr slope = 0.608, P
      = 0.00001). This predictive value was superior to, and independent from, that of
      the best conventional histological predictive parameters; tubular atrophy (R2 =
      0.477, P = 0.00004) and interstitial fibrosis (R2 = 0.28, P = 0.001). CONCLUSION:
      We have demonstrated in this study the neoexpression of cytoskeletal proteins
      within diabetic kidneys. This has allowed the identification of new predicting
      histological markers for the progression of diabetic nephropathy.

PMID- 9027773
TI  - Alternative pathway complement activation induces proinflammatory activity in
      human proximal tubular epithelial cells.
AB  - BACKGROUND: Proximal tubular epithelial cells express a surface C3-convertase
      activity which induces C fixation and insertion of the C5b-9 membrane attack
      complex (MAC) into the cell plasma membrane. The physiopathological consequences
      of this phenomenon are unknown. METHODS: The effect of C fixation on the
      production of inflammatory mediators by human proximal tubular epithelial cells
      in culture was explored. RESULTS: Proximal tubular epithelial cells incubated
      with a sublytic amount of normal human serum as a source of C, but not with heat
      inactivated human serum, showed a time-dependent calcium influx and a concomitant
      release of 14C-arachidonic acid (14C-AA). Eicosanoid synthesis following the
      arachidonic acid mobilization was studied as prostaglandin E2 release. Mg2+/EGTA,
      which did not prevent C activation by the C3-convertase, and p-bromodiphenacyl
      bromide a phospholipase A2-inhibitor, inhibited mobilization of 14C-AA. These
      results suggest the activation of an extracellular Ca(2+)-dependent,
      phospholipase A2. Complement fixation was associated with the synthesis of
      proinflammatory cytokines such as IL-6 and TNF-alpha. Experiments with C6
      deficient sera indicated that the release of 14C-AA and the production of
      cytokines were dependent on the insertion of the terminal components of
      complement in the plasma membrane. Indeed, the reconstitution of normal
      haemolytic activity of C6-deficient sera with purified C6 restored also the
      release of 14C-AA and the production of cytokines. CONCLUSIONS: In vitro
      complement activation on the proximal tubular cell surface triggers the
      generation of proinflammatory mediators, which may potentially contribute to the
      pathogenesis of tubulointerstitial injury.

PMID- 9027774
TI  - Nucleosomes and histones are present in glomerular deposits in human lupus
      nephritis.
AB  - BACKGROUND: Recently we showed that antinuclear autoantibodies complexed to
      nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane
      (GBM) via the histone part of the nucleosome. Histones have been identified in
      glomerular deposits in human and murine lupus nephritis. In addition, a decreased
      HS staining in the GBM was found, most probably due to masking by deposition of
      antibodies complexed to nucleosomes. METHODS: In this study we first investigated
      whether histones or nucleosomes could be identified in glomerular deposits in
      human lupus nephritis, and secondly whether the presence of these nuclear
      components was correlated with absence of HS staining. Kidney biopsies of SLE
      patients (11 with diffuse proliferative glomerulonephritis (DPGN) and six with
      membranous glomerulonephritis (MGN)) and non-SLE glomerular diseases were stained
      for histones. DNA, nucleosomes, IgG and HS. RESULTS: Using a polyclonal anti-H3 1
      21 antiserum, histones were detected in all patients with DPGN and in two of six
      patients with SLE-MGN (P < 0.01). Using a monoclonal antihistone antibody,
      histones were stained in three patients with DPGN, but in none of the biopsies
      with MGN. Using nucleosome specific monoclonal antibodies, nucleosomes were
      detected in five patients with DPGN, in two patients with MGN, but in none of the
      biopsies with non-SLE glomerulonephritis. HS staining was nearly absent in DPGN,
      whereas staining was only moderately reduced in patients with MGN and controls (P
      = 0.001). CONCLUSION: Using polyclonal and monoclonal antihistone antisera,
      histones were identified in all patients with DPGN and their presence was
      associated with a decrease of HS staining. Nucleosomes were identified in five of
      11 patients with DPGN and in two of six patients with MGN. This is the first
      demonstration of nucleosomes in glomerular deposits in SLE nephritis.

PMID- 9027775
TI  - Assessment of radioisotopic micturating cystography for the diagnosis of
      vesicoureteric reflux in renal transplant recipients with acute pyelonephritis.
AB  - BACKGROUND: The gold standard for documenting vesicoureteric reflux is direct
      (retrograde) micturating cystography (MC). In children, radioisotopic MC has been
      advocated for increased sensitivity and lesser radiation exposure. In renal
      transplant recipients, where reflux can induce acute pyelonephritis, this
      technique has not been evaluated. The aim of this study was to assess the
      radioisotopic technique in these patients. METHODS: Seventeen renal transplant
      recipients had developed acute pyelonephritis following the surgical grafting
      procedure. They were investigated using both MC techniques. Radioisotopic MC was
      performed using 99mTc-pertechnetate. RESULTS: Reflux was documented in nine
      patients by radioisotopic MC but in only seven with the conventional technique.
      All negative patients remained symptom free after the pyelonephritis was cured
      and it was assumed that they had no reflux. Consequently, using the radioisotopic
      MC as gold standard, the conventional X-ray technique had a sensitivity of 78%
      and a specificity of 100%. CONCLUSIONS: Direct radioisotopic MC allowing
      continuous cystogram recording is more accurate than conventional X-ray MC for
      the diagnosis of vesicoureteric reflux in transplanted patients with acute
      pyelonephritis.

PMID- 9027776
TI  - The diagnosis and racial origin of 394 patients undergoing renal biopsy: an
      association between Indian race and interstitial nephritis.
AB  - BACKGROUND: There is a high incidence of renal disease in the ethnically Indian
      population in the United Kingdom, the pathological basis for which is only partly
      understood. This study attempted to define associations between renal biopsy
      diagnosis and race. The aim was thereby to identify types of renal disease which
      may contribute to the observed predisposition to renal failure in the Indian
      population served by our centre. METHOD: A single-centre-based retrospective
      analysis of the final diagnosis and corresponding ethnicity in 394 consecutive
      patients undergoing native renal biopsy for the investigation of abnormal renal
      function or urinary sediment. RESULTS: A highly significant association between a
      diagnosis of interstitial nephritis and Indian race was observed. There were 30
      cases of interstitial nephritis, of whom 17 were Indian. In 15 of the Indian
      patients no aetiology could be established. The clinical features, outcomes, and
      the effect of steroid therapy in the Indian patients with idiopathic interstitial
      nephritis are described. CONCLUSION: Idiopathic interstitial nephritis is
      associated with Indian racial origin. This pathology may significantly contribute
      to the high incidence of end-stage renal failure in Indian patients resident in
      the United Kingdom.

PMID- 9027777
TI  - Accuracy of the urinary albumin titrator stick 'Micral-Test' in kidney-disease
      patients.
AB  - BACKGROUND: A quick, accurate, and easy measurement of microalbuminuria can be
      useful for the management of many patients. The Micral-Test stick (Boehringer
      Mannheim, Germany) gives a semiquantitative estimation of urinary albumin
      concentration at discrete readings of 0, 10, 20, 50 or 100 mg/l. The purpose of
      this study was to test its accuracy. METHODS: From 46 non-diabetic patients, 491
      urinary samples were analysed both with Micral-Test and with immunochemical
      nephelometry. RESULTS: Of 491 samples, 308 were from non-proteinuric patients
      (urinary albumin < 300 mg/day). In these patients the correlation coefficient of
      nephelometric values versus the stick readings was 0.79: 120/123 samples from non
      microalbuminuric (< or = 30 mg/24 h) and 164/185 from microalbuminuric patients
      were correctly identified by the stick, giving an 89% sensitivity and a 98%
      specificity. The readings around the threshold for microalbuminuria (20 and 50
      mg/l patches) were the most reliable ones. Analysis of the correct/uncorrect
      readings' ratio for every patch in the 245 samples in the 0-150 mg/l range shows
      a relative uniformity (chi2 = 8.5, P = 0.07), while analysis of the
      over/correct/underreadings for the 10, 20 and 50 patches, shows that incorrect
      responses tend to be underestimations for the 10 patch and overestimations for
      the 20 and 50 mg/l patches (chi2 = 10.5, P = 0.03). CONCLUSIONS: The Micral-Test
      stick is useful for screening, but less reliable for follow-up, unless
      considerable changes in albumin excretion are expected.

PMID- 9027778
TI  - Chinese herbs nephropathy presentation, natural history and fate after
      transplantation.
AB  - BACKGROUND: Chinese herbs nephropathy is a new type of subacute interstitial
      nephropathy reported in women who had followed a slimming regimen including
      Chinese herbs. METHODS: We report the clinical presentation and follow-up of 15
      cases and compare them with a control group of 15 women with interstitial
      nephropathies of other origins, matched for age, sex, and initial serum
      creatinine (mean 3 mg/dl). RESULTS: At presentation the Chinese herbs nephropathy
      group differed from the control group by a lower proteinuria (P = 0.009), a more
      severe anaemia (P = 0.002), and a higher prevalence of aortic insufficiency (42%
      vs 0%, P < 0.05). It was further characterized by mild hypertension in 80%,
      glycosuria and leukocyturia in 40% and asymmetric kidneys in 54% of the cases.
      During follow-up, deterioration of renal function was faster in the Chinese herbs
      nephropathy than in the control group (P < 0.05). It was influenced by the
      duration of Chinese herbs treatment (P = 0.037) and the delay between the end of
      Chinese herbs ingestion and diagnosis of the disease (P = 0.013). In three cases,
      renal failure developed 3 years after Chinese herbs ingestion. Complications
      included severe aortic regurgitation requiring surgery (n = 1), urothelial
      carcinoma (n = 2), bilateral ureterohydronephrosis due to periureteral fibrosis
      (n = 1). Five patients with Chinese herbs nephropathy were successfully
      transplanted, without evidence of recurrence of the disease. CONCLUSIONS: Chinese
      herbs nephropathy is characterized by a lower proteinuria, more severe anaemia,
      and a faster progression to renal failure than other interstitial nephropathies.
      The duration of Chinese herbs treatment and interval between withdrawal of
      Chinese herbs and diagnosis are correlated with the rate of progression. Severe,
      unusual extrarenal complications may affect Chinese herbs nephropathy patients.

PMID- 9027779
TI  - Effect of treatment with simvastatin on serum cholesteryl ester transfer in
      patients on dialysis. PERFECT Study Collaborative Group.
AB  - BACKGROUND: Plasma cholesteryl ester transfer activity is increased in patients
      with chronic renal failure on dialysis who have elevated levels of apolipoprotein
      B (apoB)-containing lipoproteins. Simvastatin, a 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG CoA) reductase inhibitor, reduces levels of these lipoproteins
      but the effect of treatment on cholesteryl ester transfer activity in patients on
      dialysis remains to be determined. METHODS: We measured serum newly synthesized
      cholesteryl ester transfer (NCET) activity, lecithin:cholesterol acyltransferase
      (LCAT) activity and serum lipid, lipoprotein and apolipoprotein concentrations
      before and immediately after 6 months treatment with simvastatin (10 mg daily, n
      = 24) or placebo (n = 29) in 53 patients with chronic renal failure receiving
      haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). RESULTS:
      Simvastatin therapy significantly reduced serum cholesterol, LDL cholesterol,
      apoB concentrations, and both NCET (P = 0.001) and LCAT (P = 0.012) rates. The
      decrease in NCET activity was correlated significantly with the corresponding
      decrease in apoB concentration (r = 0.715, P < 0.001) and LCAT activity (r =
      0.715, P < 0.001) during simvastatin therapy and was no longer significant when
      apoB concentration (P = 0.14) or LCAT activity (P = 0.07) were controlled.
      CONCLUSIONS: These data show that simvastatin therapy reduces serum NCET rates,
      and suggest that this may be linked to the concomitant decrease in levels of apoB
      containing lipoproteins which are acceptors of transferred cholesteryl esters,
      and to the decrease in serum LCAT rates in patients with chronic renal failure
      with treatment.

PMID- 9027780
TI  - Immunocytochemical detection of a reduction in 1,25 dihyroxyvitamin D3 receptor
      expression in uraemic parathyroid tissue.
AB  - BACKGROUND: The vitamin D receptor is expressed in nuclei of parathyroid cells
      and plays an important role in the regulation of cell growth and parathyroid
      hormone secretion. A number of studies have shown reduced receptor expression in
      uraemic parathyroid glands but the relationship between receptor expression and
      renal function has not been identified. METHODS: This study used archive
      parathyroid tissue from patients with primary adenomas, dialysis patients with
      diffuse hyperplasia secondary to uraemia and normal parathyroid tissue. An
      immunocytochemical assay with a vitamin D receptor antibody was used to identify
      parathyroid cells expressing receptor in their nuclei. RESULTS: In patients with
      a serum creatinine < or = 110 mumol/l, 81.94% +/- 6.5 of parathyroid cells
      expressed vitamin D receptor. This fell to a mean of 49.3% in two patients with a
      serum creatinine between 110 and 300 mumol/l and to 40.17% +/- 8.6 in dialysis
      patients. CONCLUSION: Vitamin D receptor expression in parathyroid glands is
      reduced in renal failure.

PMID- 9027781
TI  - Technetium-99m methoxy isobutyl isonitrile (MIBI) imaging of the parathyroid
      glands in patients with renal failure.
AB  - BACKGROUND: Technetium-99m methoxy isobutyl isonitrile (Tc-99m MIBI) scintigraphy
      has been reported to be at least as reliable as thallium-technetium subtraction
      imaging in the preoperative localization of hyperplastic parathyroid glands in
      patients with renal failure. Reports have suggested that 50% of glands can be
      identified correctly by this method. The aim of this study was to improve on
      previous results and demonstrate that Tc-99m MIBI imaging has an important place
      in the preoperative work-up of these patients. METHODS: Eighteen patients on
      renal replacement therapy were studied. All had tertiary hyperparathyroidism and
      had Tc-99m MIBI imaging prior to parathyroidectomy. A refined reporting method
      was employed. The imaging results were compared to the subsequent surgical and
      histological findings. RESULTS: In the 12 patients in whom serum parathyroid
      hormone levels fell postoperatively to within or below the normal range, 38 of 46
      glands (82.6%) were correctly identified and located in the correct quadrant of
      the thyroid gland. There were two false positive results where the imaging
      predicted glands not subsequently found by the surgeon. In the patients who had
      post-operative hyperparathyroidism, repeat Tc-99m MIBI imaging was able to locate
      accurately the site of the residual parathyroid tissue. CONCLUSIONS: Tc-99m MIBI
      imaging is able to identify more than 80% of hyperplastic parathyroid glands in
      renal failure patients if this reporting process is used, and locate them in the
      correct quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value
      when re-exploration of the neck is required for post-parathyroidectomy
      hyperparathyroidism. These results represent a significant improvement on the
      sensitivity of this imaging technique when compared to previous published data.

PMID- 9027782
TI  - Impact of the method of calculation on assessment of the PTH-calcium set point.
AB  - BACKGROUND: Although the methodology for calculating the PTH secretory parameters
      is well established, a consensus on a common methodology for calculation of the
      set point value has not yet been achieved. This is probably one of the major
      reasons for the conflicting results obtained for this secretory parameter. The
      aim of the present study was to analyse the influence of the different methods of
      calculation on the values of set point obtained in clinical nephrology practice.
      METHODS: We analysed 68 PTH-calcium sigmoidal curves, obtained by infusion of 37
      mg/kg Na2-EDTA i.v. in 2 h and 8 mg/kg Ca gluconate based on the calcium element
      i.v. in 2 h on two separate days. The set point was calculated according to three
      different methods: method A, the originally described method, based on the
      classical four-parameter model, which considers the set point as the calcium
      concentration corresponding to the PTH value intermediate between the maximal and
      minimal values (the midrange value method); method B (set point = calcium
      concentration corresponding to 50% of maximal PTH), and method C (set point =
      calcium concentration corresponding to 50% inhibition of basal PTH value). The
      three different sets of set point values were entered into the formula of the
      sigmoidal curve to test the best fitting of the PTH experimentally observed
      values. RESULTS: The set point values calculated with the classical midrange
      value method were lower than the corresponding values calculated by the other two
      methods; method C gave the highest values. Furthermore the best fitting of the
      experimentally observed PTH levels was obtained by method A the worst by method
      C, while method B gave intermediate results. The difference between method A and
      method B was analysed in order to see if this difference is constant over the
      whole range of PTH secretory conditions and calcium concentrations. The higher
      the basal serum calcium concentrations and the lower the suppressibility of PTH,
      the greater was the overestimation of set point values by method B compared to
      the midrange value method. CONCLUSIONS: Method A, the midrange value method,
      gives the set point values closest to the original concept of the four parameter
      model. Although method B (50% of maximal PTH) is well correlated with the
      original method, it overestimates the set point values and most importantly, this
      overestimation is not constant, but largely affected by calcium concentration and
      by the secretory conditions of parathyroid glands.

PMID- 9027783
TI  - Haemodialysis without anticoagulant: haemostasis parameters, fibrinogen kinetic,
      and dialysis efficiency.
AB  - BACKGROUND: Haemodialysis without anticoagulant is an alternative to systemic
      anticoagulation of patients at high risk of bleeding. However, reports have
      suggested that heparin-free haemodialysis might results in blood defibrination,
      and fibrin deposition in dialytic membrane with possible reduction in dialyser
      efficiency. METHODS: Haemostasis parameters, fibrin-fibrinogen kinetic assessed
      by 125I-fibrinogen (125I-F) turnover and 125I-fibrinogen deposition within the
      dialyser membranes, and dialytic efficiency were studied in 10 stable chronic
      uraemic patients. Each patient was dialysed on two consecutive 4-h dialyses, once
      with each of two dialysis strategies: haemodialysis without anticoagulant and
      conventional haemodialysis using heparin as anticoagulant. RESULTS: No
      significant changes were seen in mean platelet count, plasma fibrinogen,
      prothrombin time, and antithrombin III during haemodialysis without
      anticoagulation, and these parameters were not different from those in patients
      who underwent conventional haemodialysis. Compared with the predialysis values, a
      shortening of the mean aPTT from an initial mean value was noted (P < 0.05) in
      haemodialysis without anticoagulation at 60, 120 and 240 min. Fibrin-fibrinogen
      degradation products remained unchanged during conventional haemodialysis, but
      were increased after the 30th minute of haemodialysis without anticoagulation (P
      < 0.05), although all values were in normal range. The biological half-life of
      125I-F in uraemic patients before the haemodialysis was 5.02 +/- 0.43 days
      (control). There was a significant fall in 125I-F half-life during haemodialysis
      without anticoagulation (2.56 +/- 0.58 days; P < 0.01) but not during
      conventional haemodialysis (4.77 +/- 0.97, NS). After use each dialyser was
      dismantled and 125I-F deposition within the membranes (M#5, M#12 and M#19) was
      measured. During haemodialysis without anticoagulation mean fibrin deposition in
      M# (28.74 +/- 10.50 x 10(3) counts), M#12 (26.42 +/- 9.06 x 10(3) counts), and
      M#19 (21.97 +/- 8.33 x 10(3) counts) was greater (P < 0.001) than that during
      conventional haemodialysis (1.70 +/- 0.92 x 10(3), 1.33 +/- 0.65 x 10(3), and
      1.59 +/- 1.03 x 10(3) counts respectively). However, this greater deposition of
      fibrin on membranes during haemodialysis without anticoagulation did not change
      dialyser efficiency as assessed (haemodialysis without anticoagulation vs
      conventional haemodialysis) by change in serum urea (-53.96 +/- 3.38% vs -51.96
      +/- 5.20%, NS), serum creatinine (-48.65 +/- 5.99% vs -49.59 +/- 6.65%, NS),
      serum potassium (-30.06 +/- 4.46% vs -27.64 +/- 2.81%, NS), serum bicarbonate
      (+25.91 +/- 1.39% vs +24.89 +/- 2.59%, NS) and haematocrit (+3.20 +/- 3.99% vs
      2.15 +/- 2.01%, NS). The mean Kt/V was similar for conventional haemodialysis
      (0.870 +/- 0.074) and haemodialysis without anticoagulation (0.873 +/- 0.107).
      CONCLUSION: In conclusion, although conventional haemostasis parameters remained
      unchanged during haemodialysis without anticoagulation, some degree of activation
      of coagulation system occurs, haemodialysis without anticoagulation was
      associated with greater decline in 125I-F half-life and greater fibrin deposition
      on dialyser membranes, but with no change in dialyser efficiency.

PMID- 9027785
TI  - Physiological abnormalities of skeletal muscle in dialysis patients.
AB  - BACKGROUND: Muscle weakness is a common but unexplained feature of dialysis
      patients. This study investigated the prevalence and causes of muscle weakness in
      dialysis patients by examining the quadriceps muscle force and contractile
      properties. METHODS: The quadriceps femoris was studied in terms of force, force
      frequency curve, and speed of muscle relaxation in 49 dialysis patients and 27
      healthy subjects. In addition nutritional, haematological, biochemical, and
      histological assessments were performed, and steps of force generation were
      analysed to reach the possible mechanisms leading to the observed weakness.
      RESULTS: Muscle weakness, though invariable as a symptom, was subtle or absent on
      clinical examination. Quadriceps force measurements, however, revealed
      unequivocal weakness in most of the patients (71%). The quadriceps muscle was
      weaker (317 +/- 115 versus 460 +/- 159 N, P < 0.01) compared to healthy
      individuals, but there was no evidence of impaired excitation-contraction
      coupling (0.79 +/- 0.05 versus 0.76 +/- 0.07, P = 0.1). Among dialysis patients
      the older and the malnourished (n = 23) were the weaker but there was no
      relationship to the type or duration of dialysis. The serum albumin was the only
      biochemical parameter related to the muscle force (r = 0.6, P = 0.01). The other
      most prominent abnormality of quadriceps muscle function observed in this study
      was slowing of relaxation (patients versus controls; 8.7 +/- 1.8% versus 10.8 +/-
      1.1% force loss/10 ms, P < 0.0001) particularly in the malnourished group
      (malnourished versus well nourished; 8.3 +/- 2.1 versus 9.4 +/- 0.95, P = 0.03).
      Muscle histology was investigated (n = 12) and revealed that type II fibres were
      mildly atrophic in 40% of the biopsies in most areas, but predominantly type IIB.
      Although type IIB fibre areas are slightly smaller in the dialysis patients
      compared to the controls, this was not statistically significant (3025 +/- 578
      versus 4406 +/- 1582, P = 0.1) except in the malnourished group compared to the
      well-nourished dialysis patients (2092 +/- 304 versus 4346 +/- 1496, P = 0.04),
      and in the malnourished dialysis patients type IIB fibre area was significantly
      correlated to the strength (r = 0.6, P = 0.02). CONCLUSIONS: The only significant
      predictor of loss of muscle strength and abnormality of relaxation in this study
      was the nutritional state. A regular assessment of the nutritional state is
      required to ensure adequate nutrition to prevent the observed abnormalities of
      the skeletal muscles.

PMID- 9027784
TI  - Interleukin-1 receptors and receptor antagonist in haemodialysis.
AB  - BACKGROUND: Biological activity of interleukin-1 (IL-1) depends on the number and
      type of IL-1 receptors on target cells and on the amounts of its naturally
      occurring inhibitor, the IL-1 receptor antagonist (IL-1ra). METHODS: Expression
      of IL-1 receptor was studied on the peripheral blood mononuclear cells of 20 end
      stage renal-disease patients maintained by chronic haemodialysis by means of
      either polysulphone (10 patients) or cuprophane membranes (10 patients) and
      compared to that of normal controls. Plasma and cellular levels of IL-1ra and IL
      1 beta were also measured. RESULTS: The proportion of monocytes expressing the IL
      1 receptor was strikingly higher in haemodialysis patients than in the healthy
      population. This proportion further increased during haemodialysis with
      cuprophane but not with polysulphone. Expression of the IL-1 receptor on
      lymphocytes was very low in both controls and dialysed patients; in the latter
      there was no intradialytic variation. Plasma concentrations of IL-1 beta and IL
      1ra were elevated in haemodialysis patients and undetectable in controls. Whereas
      plasma IL-1 beta decreased throughout haemodialysis, IL-1ra further increased,
      with no significant differences between the two membranes used. Total cellular IL
      1 beta and IL-1ra were also higher in the patient group than in the healthy
      controls. A further increase of both IL-1 beta and IL-1ra was detected at the end
      of the haemodialysis session with any membrane. CONCLUSIONS: Monocytes of
      haemodialysis patients circulate in a state of activation, which makes them both
      producer and target of IL-1. Thus there is an autocrine upregulation of IL-1
      production. Although IL-1ra levels are high, they are most likely to be
      expression of monocyte activation rather than represent effective inhibitors of
      IL-1 activity.

PMID- 9027786
TI  - Muscular strength and bone mineral density in haemodialysis patients.
AB  - PURPOSE: The objective of this study was to determine the relationship between
      muscular strength and bone mineral density (BMD) in patients undergoing regular
      haemodialysis. METHODS: The BMD was measured in the lumbar spine (L2-L4) and in
      the proximal femur (femoral neck and trochanter) with dual-energy X-ray
      absorptiometry DEXA (Lunar DPX). Muscular strength of the extensors, flexors and
      abductors muscles of the femur (proximal muscles) and the extensors muscles of
      the back was measured with an isometric dynamometer. Thirty patients, 15 women
      with a mean age of 33.7 years (18-43) and 15 men with a mean age of 45.5 years
      (18-65) were included in the study. RESULTS: There was a positive and significant
      correlation between the BMD of the femoral neck and muscular strength of the
      flexors (r = 0.490, P < 0.005), the extensors (r = 0.658, P < 0.01) and the
      abductors muscles of the femur (r = 0.671, P < 0.0008), as well as between the
      muscular strength of the flexors (r = 0.413, P < 0.02) and extensors muscles of
      the femur (r = 0.433, P < 0.01) with BMD of the trochanter. There was no
      correlation between the muscular strength of the back extensor muscles and the
      BMD of the lumbar spine (r = -0.119, P NS). There was no correlation between the
      BMD and the number of years of haemodialysis therapy (r = -0.032, P NS), the
      patient's age (r = -159, P NS), or the value of serum PTH (r = 0.369, P NS)
      respectively. However, there was a significant correlation between the BMD of the
      femoral neck with muscular strength (r = 0.602, P < 0.05). CONCLUSION: This study
      reveals the close relationship that exists between muscular strength of the
      proximal muscles and the BMD of proximal femur in patients undergoing
      haemodialysis.

PMID- 9027787
TI  - Hepatitis E virus infection in haemodialysis patients: a seroepidemiological
      survey.
AB  - BACKGROUND: Hepatitis E virus (HEV) is the causative agent for enteric non-A, non
      B hepatitis. Transmission is via the faecal route but the possibility of
      transmission by blood has been raised. Data concerning anti-HEV prevalence among
      chronic haemodialysis (HD) patients are few and give conflicting results.
      METHODS: We tested for anti-HEV antibody 204 chronic HD patients attending a
      single dialysis unit. A specific solid-phase enzyme-linked immunoassay (Abbott
      HEV EIA) was used. RESULTS: We found six anti-HEV-positive patients, the anti-HEV
      prevalence was 3% (95% CI 0-6%). The prevalence rates of HBV and HCV infections
      were 39% (31-45%) and 22% (16-28%) respectively. No anti-HEV-positive patient
      showed past or current biochemical signs of liver damage. One of six (17%) anti
      HEV-positive patients was an immigrant; no risk factor for anti-HEV antibody was
      identified in the other anti-HEV-positive individuals. CONCLUSIONS: We observed a
      low anti-HEV prevalence: there was no association between HEV and blood-borne
      infections (HBV, HCV, and HIV) in our HD patients; most anti-HEV-positive
      patients we found were probably related to a local infection by HEV. This is one
      of the first reports concerning seroepidemiology of HEV infection in a large
      cohort of chronic HD individuals.

PMID- 9027788
TI  - Pharmacokinetics of carboplatin and etoposide in a haemodialysis patient with
      Merkel-cell carcinoma.
AB  - We present a Merkel-cell carcinoma patient with chronic renal failure requiring
      haemodialysis and evaluate the pharmacokinetics of carboplatin and etoposide
      during haemodialysis. The area under the concentration-time curve of carboplatin
      was increased by prolonging the interval between administration and
      haemodialysis. However, that of etoposide was not changed. Carboplatin showed
      good membrane permeability in haemodialysis, while etoposide showed no
      permeability. In conclusion, the pharmacokinetics of carboplatin could be
      controlled by haemodialysis and the interval between chemotherapy and
      haemodialysis. However, the pharmacokinetics of etoposide were not affected.

PMID- 9027789
TI  - Influence of variation at the apolipoprotein E locus on lipid and lipoprotein
      levels in CAPD patients.
AB  - BACKGROUND: Variation at the apolipoprotein E (apo E) locus influence lipid and
      lipoprotein levels in the normal population, and is associated with premature
      coronary artery disease. Patients with end-stage kidney disease or undergoing
      dialysis treatment are particularly prone to develop accelerated atherosclerosis.
      METHODS: To evaluate the influence of genetic variation at the apo E locus, apo E
      genotypes and serum lipid and lipoprotein levels were measured in 51 subjects
      undergoing continuous ambulatory peritoneal dialysis (CAPD). RESULTS: The
      distribution of apo E phenotypes and apo E allelic frequency among the CAPD
      subjects (epsilon 2 0.049; epsilon 3 0.745: epsilon 4 0.206) corresponded to the
      healthy Swedish population. In the CAPD subjects, total serum and LDL cholesterol
      levels were high (6.7 +/- 1.5 mmol/l and 4.2 +/- 1.3 mmol/l respectively) and HDL
      cholesterol levels were low (1.2 +/- 0.5 mmol/l). When directly comparing the two
      major apo E groups. E 3/3 subjects (n = 30) and E4/3 and 4/4 subjects, epsilon 4
      carriers, (n = 16), LDL cholesterol levels were significantly higher among
      epsilon 4-carriers (4.8 +/- 1.1 vs 4.0 +/- 1.2 mmol/l, P < 0.03), but total serum
      cholesterol levels was not higher among the epsilon 4-carriers (7.3 +/- 1.3 vs
      6.5 +/- 1.5 mmol/l, P < 0.08). Serum triglycerides or HDL cholesterol levels did
      not differ significantly between epsilon 3-homozygotes and epsilon 4-carriers.
      CONCLUSIONS: The results demonstrate a strong effect of variation of the apo E
      locus on LDL cholesterol levels in CAPD subjects, suggesting that epsilon 4
      carriers may be more susceptible to accelerated development of atherosclerosis in
      this condition.

PMID- 9027790
TI  - The influence of peritoneal dialysis and the use of subcutaneous and
      intraperitoneal insulin on glucose metabolism and serum lipids in type 1 diabetic
      patients.
AB  - BACKGROUND: Intraperitoneally administered insulin is regarded as the most
      physiological replacement therapy, leading to lower peripheral insulin
      concentrations and equal or better glycaemic control than subcutaneous insulin.
      This two-part study was undertaken to evaluate the effect of CAPD, as well as the
      use of subcutaneous vs. intraperitoneal insulin on insulin sensitivity, glycaemic
      control and serum lipids in type 1 diabetes. METHODS: Eleven patients with type 1
      diabetes mellitus and chronic renal failure participated the studies. Glycated
      haemoglobin (HbA1c), euglycaemic hyperin-sulinaemic clamp, serum lipids, and
      patient well-being were measured. During CAPD all patients were first treated
      with subcutaneous insulin and then with intraperitoneal insulin. The metabolic
      studies were repeated after both treatment periods for at least 3 months.
      Metabolic studies were performed on six of the patients also before initiation of
      CAPD. RESULTS: HbA1c rose after the initiation of CAPD from 8.85 +/- 0.54% to
      9.58 +/- 0.66%, NS) and improved after changing from subcutaneous to
      intraperitoneally administered insulin (from 9.49 +/- 0.43% to 8.13 +/- 0.39%, P
      < 0.01). Insulin dose increased by 15% after initiation of CAPD and 128% after
      switching from subcutaneous to intraperitoneal insulin. Glucose disposal rate
      enhanced by 39% (P = 0.05) and 14% respectively (P < 0.01). Initiation of CAPD
      had no significant effects on serum lipids but intraperitoneally administered
      insulin reduced HDL cholesterol and increased LDL/HDL ratio significantly.
      CONCLUSIONS: Intraperitoneal insulin therapy offers better glycaemic control and
      insulin sensitivity than subcutaneous insulin. Deterioration of HbA1c after
      initiation of CAPD while patients remained on subcutaneous insulin may be partly
      due to absorbed energy from the dialysate. Intraperitoneal insulin therapy seems
      to have detrimental effects on serum lipids. The clinical significance in
      modifying the risk of atherosclerosis remains unclear.

PMID- 9027791
TI  - Assessment of total body water and lean body mass from anthropometry, Watson
      formula, creatinine kinetics, and body electrical impedance compared with
      antipyrine kinetics in peritoneal dialysis patients.
AB  - BACKGROUND: Indirect methods such as anthropometry (A), Watson formula (W),
      creatinine kinetics (CK), and body electrical impedance (BEI) are increasingly
      applied to determine total body water (TBW) and lean body mass (LBM) in dialysis
      patients. These methods share the disadvantage that they have been validated for
      healthy men only. We studied which of these four commonly applied methods can
      best be used routinely in CAPD patients. METHODS: TBW estimates obtained from A,
      W, CK, and BEI were compared with those obtained by a gold standard (antypirine
      distribution volume, ADV) in eight CAPD patients. In addition, several BEI
      equations to derive lean body mass (LBM) were compared with LBM estimated by ADV
      in order to determine which equation is the most valuable for the assessment of
      LBM by BEI in CAPD patients. RESULTS: TBW as ADV was 41.4 +/- 6.6 (mean +/- SD)
      L. TBW estimated by W, A and CK underestimated ADV by a mean +/- SD of 2.3 +/-
      13, 5 +/- 8.4 and 12.3 +/- 10.9% respectively. TBW as measured by BEI
      overestimated ADV by 2.5 +/- 8.8%. The correlation coefficients between ADV-TBW
      and TBW estimated by the indirect methods were r = 0.88 (A), r = 0.87 (BEI), r =
      0.82 (CK), and 0.68 (W). LBM estimated by ADV was 56.7 +/- 8.9 (mean +/- SD) kg;
      LBM by different BEI equations ranged from 49.9 +/- 7 to 58.1 +/- 10.7 kg. The
      correlation coefficient between LBM by ADV and LBM according to the various BEI
      equations ranged from 0.81 to 0.93. CONCLUSION: A and BEI can be used to estimate
      TBW, but the considerable SD (or inaccuracy) makes individual predictions
      hazardous. Considering the correlation coefficients and difference between LBM by
      ADV and LBM according to different BEI equations, Deurenberg's formula can be
      advocated for use in the estimation of LBM by BEI.

PMID- 9027792
TI  - One-dose cefuroxime i.v. and i.p. reduces microbial growth in PD patients after
      catheter insertion.
AB  - BACKGROUND: When a peritoneal dialysis catheter is inserted intra-abdominally in
      a patient starting peritoneal dialysis (PD) there is always a risk for
      postoperative wound infection and peritonitis. At our centre, PD is started
      immediately after the dialysis catheter is inserted. This may increase the
      postoperative risk for peritonitis and wound infection. The aim of this
      prospective, randomized, study was to evaluate whether the incidence of microbial
      growth postoperatively (within 10 days) after catheter insertion could be reduced
      by prophylactic antibiotic therapy. SUBJECTS AND METHODS: During a period of 27
      months, 38 patients, who consecutively entered the PD programme, (11 women and 27
      men, mean age 57 years) were included in the study. Eighteen patients were given
      cefuroxime 1.5 g i.v. preoperatively and 250 mg i.p. in the first dialysis bag
      (containing 1 litre fluid) as prophylaxis. Twenty patients were not given
      prophylactic antibiotics (control group). All catheter insertions were performed
      in an operating theatre by the same surgeons using the same technique. RESULTS:
      In the test group, none of the patients showed microbial growth in the dialysis
      fluid during the post-operative period, while in the control group six of 20
      patients (30%) suffered from such growth (P = 0.021). CONCLUSION: Prophylactic
      treatment by cefuroxime i.v. pre- and i.p. perioperatively may reduce the risk
      for microbial growth and peritonitis after insertion of a Tenckhoff catheter.

PMID- 9027793
TI  - Serum amyloid A protein is a clinically useful indicator of acute renal allograft
      rejection.
AB  - BACKGROUND: Early diagnosis of acute rejection after renal transplantation is
      important. There is evidence that measurement of the acute phase proteins, C
      reactive protein (CRP) and serum amyloid A protein (SAA) is helpful. METHODS: In
      64 consecutive patients, CRP was measured in a routine clinical system (Technicon
      RA1000, Bayer) and SAA in a new sensitive automated immunoassay on the Abbott IMx
      instrument, daily or on alternate days for 30 days after renal transplantation.
      RESULTS: Patients all received triple immunosuppression with cyclosporin,
      azathioprine, and prednisolone and all mounted a post-surgical acute phase
      response of SAA, but the CRP response was reduced or absent. Serum creatinine
      rose significantly in 36 patients, leading to treatment for first rejection.
      Thirty of these episodes were confirmed rejection, three were definitely not and
      three were uncertain. SAA. normally < 10 mg/l, rose to more than 100 mg/l in all
      episodes except when rejection was definitely absent. In six cases SAA rose above
      100 mg/l 1-3 days before the rise in creatinine leading to antirejection therapy,
      and only twice did creatinine rise 1 day before SAA. In contrast, CRP responses
      to rejection were modest or absent. In four patients there were SAA and CRP
      responses unrelated to rejection, three associated with intercurrent infection
      and one with administration of antilymphocyte globulin. There were also two
      unexplained isolated spikes of SAA. CONCLUSIONS: SAA is a sensitive marker of
      acute renal allograft rejection. It is not specific, but the differential
      behaviour of CRP in patients receiving cyclosporin helps to distinguish infection
      from rejection. Availability of rapid assays for these analytes should facilitate
      management of renal allograft recipients.

PMID- 9027794
TI  - Environmental and genetic determinants of the hypercoagulable state and
      cardiovascular disease in renal transplant recipients.
AB  - BACKGROUND: Fibrinogen and factor VII coagulant activity (VIIc), risk factors for
      cardiovascular disease (CVD) in the general population, could contribute to CVD
      risk in renal transplant recipients (RTR). METHODS: We measured fibrinogen and
      VIIc in 38 RTR and 31 controls, along with prothrombin fragment F1 + 2 and D
      Dimer (markers of coagulation and fibrinolytic activation), plasma lipids and the
      acute phase response cytokine, interleukin 6. The effect of genetic polymorphisms
      of beta-fibrinogen (G/A-455) and factor VII (Arg/Gln353) was explored. RESULTS:
      F1 + 2, D-Dimer, and fibrinogen were increased in all RTR, indicating a chronic
      prothrombotic state. Fibrinogen correlated with age. F1 + 2, and trough
      cyclosporin A (CsA). RTR carriers of the A-455 allele had a greater increment in
      plasma fibrinogen concentration and correlation with CsA than homozygotes for the
      G-455 allele. Interleukin 6 was increased in RTR confirming that a persistent
      lowgrade acute-phase response could contribute to increased fibrinogen.
      Differences in plasma VIIc were associated with factor VII genotype, disease
      status, and blood lipids. Carriers of the Gln353 allele had 30% lower VIIc when
      compared with Arg353 homozygotes, which could confer a reduced thrombotic risk.
      The 12 RTR with CVD or metabolic complications (RTR+) were more hyperlipidaemic
      and had higher fibrinogen and VIIc than the 26 RTR free of disease complications
      (RTR-), or the controls. CONCLUSIONS: Long-term RTR manifest features of a
      chronic prothrombotic and persistent inflammatory state. Alterations in
      fibrinogen and VIIc in RTR arise in part as a result of interactions between
      common genetic and environmental factors, and these changes could contribute to
      the increased risk of CVD in RTR.

PMID- 9027795
TI  - A simple method to identify NBT-positive cells in isolated glomeruli.
AB  - BACKGROUND: Reactive oxygen radicals are probably involved in the pathogenesis of
      human and experimental models of renal disease, yet current methods are
      inadequate to quantify and identify the cells producing reactive oxygen radicals.
      METHODS AND RESULTS: We used the nitroblue tetrazolium reaction to determine
      superoxide anion production in glomerular cells in phorbol myristate-stimulated
      glomerular suspensions and in isolated glomeruli from rats with nephrotoxic
      nephritis, ureteral obstruction, and puromycin aminonucleoside nephrosis. We were
      also able to identify these nitroblue tetrazolium + cells using specific
      appropriate antibodies. When the technique was tested in conditions known to
      increase reactive oxygen radicals, as phorbol myristate-stimulated glomeruli and
      glomeruli from animals with nephrotoxic nephritis and ureteral obstruction,
      increased number of nitroblue tetrazolium + cells were found. These cells were
      identified as glomerular intrinsic cells (Thy-1 +) or infiltrating leukocytes
      (leukocyte common antigen + or antineutrophil +). CONCLUSION: This method may be
      useful to determine cells participating in glomerular damage induced by reactive
      oxygen radicals.

PMID- 9027796
TI  - Interference of creatinine measurement in CAPD fluid is dependent on glucose and
      creatinine concentrations.
AB  - BACKGROUND: High glucose concentration in CAPD fluid is known to interfere with
      creatinine measurement, which is required for assessment of peritoneal membrane
      permeability and adequacy of dialysis. Correction formulae have been proposed but
      they may be method/analyser-dependent. We studied such interference in detail.
      METHODS: CAPD fluid was diluted to prepare six specimens with glucose
      concentrations ranging from 9.1 to 154.4 mmol/l. To each specimen, creatinine
      standard was added to give five different concentrations from 50 to 800 mumol/l.
      The 30 specimens were assayed for creatinine with six routine clinical chemistry
      analysers (Hitachi 911 and 747, Technicon RAXT and SMAC3, Beckman CX7, and Kodak
      Ektachem 700). Creatinine interference was calculated by subtracting the apparent
      creatinine concentration with corresponding baseline creatinine concentration
      (measured at glucose = 9.1 mmol/l) in the same series. RESULTS: At constant
      creatinine concentration, interference increased with increasing glucose
      concentration to varying extents (up to 200%) amongst the six analysers. At
      constant glucose concentration, interference decreased with increasing creatinine
      concentration in analysers using the alkaline picrate reaction but increased in
      the Kodak analyser using enzymatic assay. CONCLUSION: Interference of creatinine
      measurement in CAPD fluid is dependent on glucose and creatinine concentrations,
      and each centre should derive specific correction formulae for its analytical
      system.

PMID- 9027797
TI  - Neurofibromatosis and renovascular hypertension presenting in early pregnancy.

PMID- 9027799
TI  - Acute inferior vena cava thrombosis in a patient with membranous nephropathy
      treated by rt-PA lysis.

PMID- 9027798
TI  - Renal manifestations of angiotrophic lymphoma: clinicopathological features.

PMID- 9027800
TI  - Thrombotic thrombocytopenic purpura following hemicolectomy for colonic
      carcinoma.

PMID- 9027801
TI  - Acute renal failure and nephrotic syndrome with alpha interferon therapy.

PMID- 9027802
TI  - Severe acute renal failure due to bromate intoxication: report of a case and
      discussion of management guidelines based on a review of the literature.

PMID- 9027803
TI  - Fibrillary glomerulonephritis in a patient with adenocarcinoma of stomach.

PMID- 9027804
TI  - IgA nephropathy associated with polycythaemia vera: accelerated course.

PMID- 9027805
TI  - Calcifying panniculitis in a child after renal transplantation.

PMID- 9027806
TI  - Nodular glomerulosclerosis after renal transplantation without diabetes mellitus.

PMID- 9027807
TI  - Isolated glomerular proteinuria as the only clinical manifestation of Fabry's
      disease in an adult male.

PMID- 9027808
TI  - Quadriparesis and faecal incontinence in a long-term haemodialysis patient.

PMID- 9027809
TI  - The patient with glomerulonephritis and lipodystrophy.

PMID- 9027810
TI  - Ascites in a polycystic patient.

PMID- 9027811
TI  - Secondary distal renal tubular acidosis in association with urological
      abnormalities.

PMID- 9027812
TI  - Lipids and lipoproteins alteration after renal transplantation.

PMID- 9027814
TI  - Biocompatible membranes in acute renal failure: prospective case-controlled
      study.

PMID- 9027813
TI  - Antiproteinuric effect of Losartan in patients with chronic renal diseases.

PMID- 9027847
TI  - Advances in SMA research: review of gene deletions.
AB  - The term spinal muscular atrophy (SMA) is used to encompass a group of inherited
      disorders in which the striking pathological feature is loss of the cell bodies
      of alpha motor neurons in the anterior horn cell of the spinal cord and, in some
      cases, of the bulbar motor nuclei. Although the pathological features of these
      disorders have been well characterized, the nature of the primary underlying
      biochemical abnormality remains to be determined. In the 1990s genetic linkage
      was established for the childhood onset recessive forms of SMA (types I, II and
      III) to markers mapping to the chromosomal region 5q11.2-13.3. Physical maps of
      the region were then constructed, several candidate genes isolated and in 1995
      deletions in two genes, the survival motor neuron (SMN) gene and the neuronal
      apoptosis inhibitory protein (NAIP) gene, were identified in significant numbers
      of patients. Already the impact of the characterization of these deletions is
      being seen in clinical practice in terms of aiding diagnosis in symptomatic cases
      and in prenatal diagnosis. As discussed in this review however, several questions
      remain unresolved. It is unclear whether deletions in one or both of these genes,
      or indeed in other, as yet unidentified, genes are important in generating the
      SMA phenotype. The function of the protein product of the SMN gene is unknown.
      The NAIP gene encodes a protein which inhibits apoptosis in a mammalian cell
      line: is it disruption of this function which is relevant in SMA? What underlies
      the variation in disease severity evident both between and within families?
      Resolution of such issues is of crucial importance if the identification of these
      deleted gene sequences is to lead to the development of rational therapies for
      motor neuron diseases.

PMID- 9027848
TI  - Merosin/laminin-2 and muscular dystrophy.
AB  - The laminins are a family of structural basement membrane components with major
      influences on cells. They are high molecular weight glycoproteins composed of
      three different but homologous chains, alpha, beta and gamma. At present 10
      different chains have been identified. Each chain has a distinct structural
      organization of domains, some of which have been assigned biological activities,
      including self-assembly and interactions with other proteins. The particular
      importance of laminins for the formation and stability of cell adhesion complexes
      is highlighted in severe inherited diseases of muscle and skin. Merosin is the
      collective name for laminins that share a common subunit, the laminin alpha 2
      chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by
      mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional
      epidermolysis bullosa is caused by mutations in any of the laminin alpha 3, beta
      3 or gamma 2 chain genes. The medical importance of laminins provides a further
      impetus to study the basic structure-function relationships in laminins in order
      to understand genotype-phenotype relationships and to design prenatal diagnostic
      tests and therapies aimed at compensating for specific defects.

PMID- 9027849
TI  - Clinical and genetic study of chronic (types II and III) childhood onset spinal
      muscular atrophy.
AB  - We have conducted a retrospective study of 63 patients affected by chronic forms
      of spinal muscular atrophy (SMA) to better document the natural history of this
      disease. Thirty-nine patients had type II and 24 type III SMA. These patients had
      manual muscle testing (MMT) and forced vital capacity (FVC) studies done every
      six to 12 months over follow up period ranging from six to 140 months. A decline
      in FVC was seen in both types of SMA but there was no significant change in MMT
      in either group. Genetic studies were also done in a subset of 17 families (23
      patients) included in this study. Homozygous deletions in the telomeric survival
      motor neuron (SMN) and the neuronal apoptosis inhibitory protein (NAIP) genes
      were observed in 100% and 11.8% of the patients tested respectively.

PMID- 9027850
TI  - Sequential study of central and peripheral nervous system involvement in an
      infant with merosin-deficient congenital muscular dystrophy.
AB  - Diffuse white matter changes on brain imaging and peripheral neuropathy are
      associated features of merosin-deficient congenital muscular dystrophy (CMD). In
      this report we describe the early manifestation and evolution of brain changes,
      and the involvement of the peripheral nervous system in a female infant with
      merosin-deficient CMD diagnosed in the neonatal period who had sequential
      clinical, neurophysiological and magnetic resonance imaging (MRI) assessment.
      Both MRI and nerve conduction velocity in the first week of life failed to
      demonstrate any abnormality. By 6 months of age both nerve conduction and MRI
      were abnormal. White matter changes became more evident on a further scan at 1 yr
      of age and this pattern remained unchanged on the following scan performed at 17
      months of age. Our findings suggest a failure in the physiological maturation
      process of myelination of both the central and peripheral nervous system.

PMID- 9027851
TI  - Respiratory insufficiency and ventilatory support. 39th ENMC International
      Workshop, Naarden, The Netherlands, 26-28 January 1996. European Consortium on
      Chronic Respiratory Insufficiency.

PMID- 9027852
TI  - Towards the classification of the autosomal recessive limb-girdle muscular
      dystrophies.

PMID- 9027853
TI  - Optimized protein diagnosis in the autosomal recessive limb-girdle muscular
      dystrophies.
AB  - The genes for six forms of recessive muscular dystrophy have so far been
      identified, although more are certain to be revealed. Differential diagnosis on
      clinical grounds alone can be very difficult, so a classification system based on
      the underlying molecular defect has been introduced. Muscle biopsies are taken
      for routine diagnostic histopathology, and the various proteins implicated in
      muscular dystrophy can be analysed immunologically and the results used to
      indicate where to start searching for gene mutations. A flow diagram is presented
      which demonstrates how such protein analysis could be optimized.

PMID- 9027854
TI  - Chromosome 15-linked limb-girdle muscular dystrophy: clinical phenotypes in
      Reunion Island and French metropolitan communities.
AB  - Erb's type limb-girdle muscular dystrophy (LGMD) was identified and clinically
      studied in detail in a small community living in the Reunion Island (RI). It was
      linked to chromosome 15q and related to mutations in the muscle specific calpain
      3 gene. A series of cases were afterwards clinically and genetically identified
      in the French metropolitan community. The phenotype was identical to the RI type
      in the great majority of cases, although clinical differences were noticed in a
      few cases. Six different mutations were identified in the RI families, whereas a
      series of 39 mutations were detected in the French metropolitan families, all
      different from those present in the RI patients. Phenotype-genotype correlations
      were attempted in both communities.

PMID- 9027855
TI  - Identification of muscle-specific calpain and beta-sarcoglycan genes in
      progressive autosomal recessive muscular dystrophies.
AB  - The autosomal recessive forms of limb-girdle muscular dystrophies are encoded by
      at least five distinct genes. The work performed towards the identification of
      two of these is summarized in this report. This success illustrates the growing
      importance of genetics in modern nosology.

PMID- 9027856
TI  - From adhalinopathies to alpha-sarcoglycanopathies: an overview.

PMID- 9027857
TI  - Abnormalities in alpha-, beta- and gamma-sarcoglycan in patients with limb-girdle
      muscular dystrophy.
AB  - We have identified 12 cases from a group of 45 patients with early onset limb
      girdle muscular dystrophy (LGMD), who have a deficiency of the 50 kDa dystrophin
      associated glycoprotein, alpha-sarcoglycan. An additional male sibling of one
      case was also studied clinically. All 12 patients showed a concomitant, but
      variable, deficiency of alpha-, beta- and gamma-sarcoglycan. None of our patients
      had a defect in only one component of the sarcoglycan complex. Molecular analysis
      confirmed that a total absence of one sarcoglycan, associated with reduced
      expression of the other two, indicates a primary defect. Immunocytochemistry is
      thus useful for directing molecular studies. Morphological features not usually
      observed in Xp21 dystrophies were peripheral accumulations of mitochondria,
      discrete core-like areas, and nemaline rods in one case. Clinical severity and
      progression was variable between and within families but early loss of
      ambulation, at or before the age of 12 years, was associated with a total absence
      of gamma-sarcoglycan. Common clinical features were calf hypertrophy,
      contractures of the tendo achilles, lumbar lordosis, winging of the scapulae,
      weak hamstrings and weak neck muscles. All cases had grossly elevated serum
      creatine kinase. In contrast to patients with Duchenne muscular dystrophy (DMD),
      our patients with sarcoglycan deficiencies had normal early motor milestones,
      normal intellect, and good respiratory and cardiac function. Our data confirm
      that the sarcoglycan complex acts as a unit and that morphological and clinical
      features can distinguish patients with defects in the sarcoglycans from those
      with Xp21 dystrophy. In our group of patients prognosis is better than in DMD,
      but clinical variability makes this difficult to predict in isolated cases.

PMID- 9027858
TI  - Autosomal recessive muscular dystrophy and mutations of the sarcoglycan complex.
AB  - Mutations in the genes encoding the dystrophin-associated sarcoglycan proteins
      (alpha, beta, gamma, and delta) (primary sarcoglycanopathies) have recently been
      shown to cause some cases of the genetically heterogeneous autosomal recessive
      muscular dystrophies (limb-girdle muscular dystrophy (LGMD) types 2D, 2E, 2C and
      2F, respectively). Patients with a primary sarcoglycanopathy are clinically
      indistinguishable from those with the primary dystrophinopathies. Consequently, a
      definitive diagnosis can only be achieved through biochemical and molecular
      analysis. Patient biopsies showing normal dystrophin immunostaining (and/or
      immunoblot) can be immunostained with antibodies directed against any component
      of the sarcoglycan complex, and biochemical deficiencies of the sarcoglycan
      complex can be detected. We have shown, however, that only some of the
      biochemically-deficient patients are affected with alpha-, beta-, gamma- and
      delta-sarcoglycan mutations. Many will show mutations of an, as yet, unidentified
      protein. The primary sarcoglycanopathies have been estimated to account for about
      5 per cent of muscular dystrophy in patients with normal dystrophin findings.

PMID- 9027859
TI  - The phenotype of chromosome 2p-linked limb-girdle muscular dystrophy.
AB  - This study reports on a detailed clinical, electrophysiological, muscle computed
      tomography (CT) and laboratory investigation carried out on five families with
      definite linkage to chromosome 2p. Some clinical and laboratory features were
      common to most of the patients, such as the very high serum creatine kinase (CK)
      levels (mean 43.70 times the normal). The onset was most frequently in the late
      teens or early twenties with weakness and wasting of the pelvic girdle muscles.
      All patients had normal motor milestones and had not complained of any symptoms
      of muscle disease in early childhood. The clinical course was variable both
      between and within some families, but was most often slowly progressive. Some
      variability in the pattern of muscle involvement between the different families
      has also been observed.

PMID- 9027860
TI  - The molecular biology of LGMD2B--towards the identification of the LGMD gene on
      chromosome 2p13.

PMID- 9027861
TI  - Limb-girdle muscular dystrophy 2C: clinical aspects.
AB  - The LGMD2C linked to chromosome 13q and related to a 35 KDa dystrophin-associated
      glycoprotein deficiency, is very similar to Duchenne muscular dystrophy with an
      autosomal recessive inheritance. It is characterized by a variability of the age
      of onset, the severity of the evolution and the severity of myopathic changes at
      the muscle biopsy. This variability was also present in the expression of the
      alpha-sarcoglycan between the same sibships and between different families.

PMID- 9027862
TI  - Neuromuscular disorders: gene location.

PMID- 9027863
TI  - Substantia innominata: a notion which impedes clinical-anatomical correlations in
      neuropsychiatric disorders.
AB  - Comparative neuroanatomical investigations in primates and non-primates have
      helped disentangle the anatomy of the basal forebrain region known as the
      substantia innominata. The most striking aspect of this region is its subdivision
      into two major parts. This reflects the fundamental organizational scheme for
      this portion of the forebrain. According to this scheme, two major subcortical
      telencephalic structures, i.e. the striatopallidal complex and extended amygdala,
      form large diagonally oriented bands. The rostroventral extension of the pallidum
      accounts for a large part of the rostral subcommissural substantia innominata,
      while the sublenticular substantia innominata is primarily occupied by elements
      of the extended amygdala. Also dispersed across this region is the basal nucleus
      of Meynert, which is part of a more or less continuous collection of cholinergic
      and non-cholinergic corticopetal and thalamopetal cells, which stretches from the
      septum diagonal band rostrally to the caudal globus pallidus. The basal nucleus
      of Meynert is especially prominent in the primate, where it is sometimes
      inappropriately applied as a synonym for the substantia innominata, thereby
      tacitly ignoring the remaining components. In most mammals, the extended amygdala
      presents itself as a ring of neurons encircling the internal capsule and basal
      ganglia. The extended amygdala may be further subdivided, i.e. into the central
      extended amygdala (related to the central amygdaloid nucleus) and the medial
      extended amygdala (related to the medial amygdaloid nucleus), which generally
      form separate corridors both in the sublenticular region and along the
      supracapsular course of the stria terminalis. The extended amygdala is directly
      continuous with the caudomedial shell of the accumbens, and to some extent
      appears to merge with it. Together the accumbens shell and extended amygdala form
      an extensive forebrain continuum, which establishes specific neuronal circuits
      with the medial prefrontal-orbitofrontal cortex and medial temporal lobe. This
      continuum is particularly characterized by a prominent system of long intrinsic
      association fibers, and a variety of highly differentiated downstream projections
      to the hypothalamus and brainstem. The various components of the extended
      amygdala, together with the shell of the accumbens, are ideally structured to
      generate endocrine, autonomic and somatomotor aspects of emotional and
      motivational states. Behavioral observations support this proposition and
      demonstrate the relevance of these structures to a variety of functions, ranging
      from the various elements of the reproductive cycle to drug-seeking behavior. The
      neurochemical and connectional features common to the accumbens shell and the
      extended amygdala are especially relevant to understanding the etiology and
      treatment of neuropsychiatric disorders. This is discussed in general terms, and
      also in specific relation to the neurodevelopmental theory of schizophrenia and
      to the neurosurgical treatment of neuropsychiatric disorders.

PMID- 9027864
TI  - Spatial cortical patterns of metabolic activity in monkeys performing a visually
      guided reaching task with one forelimb.
AB  - The 2-[14C]deoxyglucose method was used to map the metabolic activity in the
      neocortex of monkeys (Macaca nemestrina) performing a visually guided reaching
      task with one forelimb. Monkeys received liquid reward for correct, single
      directional reaching movements, which were required at a rate of about 10 per
      minute. We estimated the weighted average of local glucose consumption within
      several neocortical areas, and we reconstructed quantitative, high-resolution,
      two-dimensional maps of the detailed spatiointensive patterns of activity. Our
      findings demonstrate the involvement of the striate and prestriate cortices, the
      inferior intraparietal and superior temporal visual association areas, the
      frontal eye field and the caudal periprincipal cortex, the primary somatosensory
      and the related superior intraparietal area, the primary and association auditory
      cortices, the superior temporal multimodal region, and the premotor, primary,
      supplementary, and cingulate motor areas. The visual cortex in the superior
      temporal and the intraparietal sulci, which is concerned with "where", was
      activated during visually guided reaching. In contrast, the inferior temporal
      visual association cortex, which is concerned with "what", was not involved in
      our study. We suggest that the activated direction-selective layer four of V1 and
      the thick stripes of V2 convey visuomotor information to the activated cortex in
      the posterior bank and the floor of the superior temporal sulcus, which may
      encode the constantly updated position of the moving forelimb. In parallel, the
      activated cortex in the ventral part and the lateral bank of the intraparietal
      sulcus may encode visuospatial information related to the localization of the
      visual target in the extrapersonal space. Furthermore, the dorsal part of the
      medial bank of the intraparietal sulcus may be involved in proprioceptive
      guidance of movement, based on the parallel metabolic effects shown only
      contralateral to the moving forelimb within this region and the forelimb
      representations in the primary somatosensory and motor cortices. Finally, the
      bilaterally activated network including the inferior postarcuate skeletomotor and
      prearcuate oculomotor cortical fields and the caudal periprincipal region 46 may
      participate in sensory and oculomotor to motor transformations, in parallel with
      the medial and lateral intraparietal cortices with which this network is
      reciprocally interconnected.

PMID- 9027865
TI  - Brain cytochrome oxidase subunit complementary DNAs: isolation, subcloning,
      sequencing, light and electron microscopic in situ hybridization of transcripts,
      and regulation by neuronal activity.
AB  - The goal of the present study was to isolate, for the first time, cytochrome
      oxidase subunit genes from murine brain complementary DNA library and to
      characterize the expression of these genes from mitochondrial and nuclear sources
      at both light and electron microscopic levels. Brain subunit III (mitochondrial)
      shared 100% identity with that of murine L cells. Subunit VIa (nuclear) was known
      to have tissue-specific isoforms in other species: the ubiquitous liver isoform
      and the heart/muscle isoform. Our brain subunit VIa shared 93% homology with that
      of the rat liver and 100% identity with the recently reported murine liver
      isoform, which is only 62% identical to that of the rat heart isoform. In situ
      hybridization with riboprobes revealed messenger RNA labelling that was similar,
      though not identical, to that of cytochrome oxidase histochemistry. Monocular
      enucleation in adult mice induced a significant down-regulation of both subunit
      messages in the contralateral lateral geniculate nucleus. However, the decrease
      in subunit III messenger RNAs surpassed that of subunit VIa at all time periods
      examined, suggesting that mitochondrial gene expression is more tightly regulated
      by neuronal activity than that of nuclear ones. At the electron microscopic
      level, subunit III messenger RNA was localized to the mitochondrial compartment
      in both cell bodies and processes, while that of nuclear-encoded subunit VIa was
      present exclusively in the extramitochondrial compartment of somata and not of
      dendrites or axons. Surprisingly, the message was primarily associated with the
      rough endoplasmic reticulum, suggesting a novel pathway for its synthesis and
      trafficking. Our results indicate that the unique properties of neurons impose
      special requirements for subunits of a single mitochondrial enzyme with dual
      genomic origins. At sites of high energy demands (such as postsynaptic dendrites
      and some axon terminals), mitochondrial-encoded cytochrome oxidase subunits can
      be locally transcribed and translated, and they provide the framework for the
      subsequent importation and incorporation of nuclear-encoded subunits, which are
      strictly synthesized in the cell bodies. Dynamic local energy needs are met when
      subunits from the two genomic sources are assembled to form functional
      holoenzymes.

PMID- 9027866
TI  - Cholecystokinin B receptor antagonists enhance the locomotor response to the N
      methyl-D-aspartate antagonists phencyclidine and dizocilpine maleate.
AB  - The cholecystokinin antagonists L-740,093, L-365,260, LY-288513 and CI988, which
      are all selective for the cholecystokininB receptor subtype, were examined for
      their ability to modulate locomotor activity induced by the non-competitive N
      methyl-D-aspartate receptor antagonists phencyclidine and dizocilpine maleate (MK
      801) in habituated rats. It was found that the locomotor effects (motility,
      locomotion) produced by subcutaneous administration of phencyclidine (2 mg/kg)
      were significantly potentiated by intraperitoneal (i.p.) administration of L
      740,093 (1 mg/kg), L-365,260 (10 mg/kg), LY-288513 (10 mg/kg), but not CI-988 (10
      mg/kg). Locomotor activity induced by subcutaneous administration of MK-801 (0.15
      mg/kg) was potentiated by intraperitoneal L-740,093 (0.3, 1 and 3 mg/kg). L
      740,093, L-365,260, LY-288513 and CI-988 administered alone did not alter
      spontaneous locomotor activity (motility) as compared to vehicle/saline controls.
      However, when these antagonists were administered to naive, unhabituated rats, L
      365,260 and LY-288513 caused a significant reduction in motility compared to the
      vehicle control. These findings suggest that, although cholecystokinin may be
      involved in exploratory behaviour exhibited by rats in a novel environment
      (unhabituated rats), its role is negligible in rats subjected to a familiar
      environment (habituated rats). Furthermore, these results support the
      interpretation that cholecystokinin has a suppressant effect on locomotion
      elicited by phencyclidine and MK-801, and that this inhibitory action of
      cholecystokinin is mediated via the cholecystokininB receptor, since it can be
      eliminated by administration of cholecystokininB antagonists. It is suggested
      that the site of action of the cholecystokininB receptors involves mainly the
      cholecystokinin/glutamate projection from the cortex to the anterior nucleus
      accumbens and/or striatum. Finally, the present study provides two examples of
      endogenous release of a neuropeptide resulting in behavioural consequences.

PMID- 9027867
TI  - c-fos induction in sensory pathways of rats exploring a novel complex
      environment: shifts of active thalamic reticular sectors by predominant sensory
      cues.
AB  - In normal rats exploring a novel, complex environment, in comparison to control
      nonexploring rats, there is induction of the FOS protein, a marker of neuronal
      activity, in all layers of the striate visual cortex (particularly in the
      granular and supragranular layers), in the stratum griseum superficiale of the
      superior colliculus, and in the dorsal lateral geniculate nucleus, as well as in
      all layers of the whiskers barrel field in the somatosensory cortex. A surprising
      finding was a selective activation of the visual sector of the thalamic reticular
      nucleus, in dorsocaudal parts of the nucleus. To the contrary, in visually
      deprived rats exploring a novel environment which would depend critically on
      whiskers tactile clues for exploration there was instead a selective activation
      of the somatic sector in central parts of the thalamic reticular nucleus, in
      conjunction with activation of cortical whiskers barrel field. From these results
      it is concluded: (1) Different sensory sectors of the rat thalamic reticular
      nucleus are activated depending on prevalent sensory channels used in recognition
      of the environment, suggesting a role of thalamic reticular nucleus in optimizing
      thalamocortical transmission of essential external cues to guide adequate
      behaviour. (2) In the awake state, the granular and supragranular layers of the
      visual and somatosensory cortices are more active when attention is paid to
      sensory stimuli that are essential for recognition of the environment. (3) The
      selective induction of c-fos in the visual and somatosensory cortices, and in the
      stratum griseum superficiale of superior colliculus of rats exploring a novel,
      complex environment might be related to plastic changes that have been
      demonstrated in these centres in rats raised in complex environments. These
      plastic changes are likely to be the result of target late-response genes
      activated by c-fos.

PMID- 9027868
TI  - Reduced eticlopride-induced Fos expression in caudate-putamen and globus pallidus
      after unilateral frontal cortex injury: relation to neglect.
AB  - Unilateral ablation of medial agranular cortex in rats results in neglect of
      contralateral stimuli and reductions in amphetamine-induced expression of the
      immediate early gene, c-fos, in both caudate-putamen and globus pallidus. Both
      unilateral neglect and the reductions in dopamine agonist induction of
      subcortical Fos immunoreactivity dissipate over a matter of weeks. Dopamine
      agonism induces Fos predominantly in striatonigral cells and in globus pallidus
      via striatopallidal disinhibition, whereas Fos is induced in striatopallidal
      cells by administration of antagonists of the D2 dopamine receptor subfamily. To
      examine more directly effects of cortical injury on striatopallidal function,
      induction of striatal Fos by the D2 antagonist eticlopride (0.1 mg/kg, s.c.) was
      examined in rats with medial agranular cortex ablation. In the same animals,
      eticlopride-induced Fos in globus pallidus was also examined. Five days after
      unilateral cortex injury, in rats showing neglect, the numbers of Fos
      immunoreactive nuclei induced by eticlopride were reduced by 50% in caudate
      putamen and 25% in globus pallidus of the ipsilateral hemisphere. These lesion
      effects were restricted to dorsolateral caudate-putamen and dorsal pallidum.
      Three or more weeks after cortical injury, in rats recovered from neglect,
      eticlopride-induced Fos was normalized in caudate-putamen, but still decreased by
      20% in globus pallidus. Along with previous findings, these results suggest that
      behavioral recovery from neglect produced by cortical injury may be at least
      partially mediated by normalizations of function of both striatopallidal and
      striatonigral neurons. In addition, the present findings suggest that
      normalization of function of pallidal cells activated by eticlopride is not
      necessary for behavioral recovery from frontal cortex ablation. Lingering
      reductions in excitatory cortico-subthalamo-pallidal input may be responsible for
      the longer-lasting dysfunctions of these pallidal cells.

PMID- 9027869
TI  - Amphetamine sensitization enhances regional c-fos expression produced by
      conditioned fear.
AB  - Chronically administered amphetamine can result in a paranoid psychosis that can
      be re-induced in former amphetamine abusers by psychological stressors. In an
      attempt to investigate the neurobiological correlates of this phenomenon, the
      present study examined the effects of prior D-amphetamine sensitization on
      regional c-fos expression induced by a psychological stressor. Rats received
      intermittent footshock in a distinctive environment for 30 min/day for three
      days. Three days after the last fear conditioning session, the animals received
      injections of saline or D-amphetamine (4 mg/kg, i.p.) once every second day for
      16 days (eight injections in total). After a 14-day drug abstinent period, the
      animals were placed in the fear conditioning apparatus but without footshock. The
      amphetamine sensitization procedure significantly enhanced the effects of
      conditioned fear on c-fos expression in several brain regions. These included the
      cingulate cortex area 3, agranular insular cortex (layers 2 and 3), claustrum,
      piriform cortex, the shell region of the nucleus accumbens, medial striatum,
      ventral lateral septum, and CA3 and polymorphic layer of the hippocampal
      formation. These results indicate that D-amphetamine sensitization can have long
      lasting effects on the neural circuitries activated by conditioned stressors.

PMID- 9027870
TI  - Feeding-evoked dopamine release in the nucleus, accumbens: regulation by
      glutamatergic mechanisms.
AB  - The extent to which glutamate receptors in the nucleus accumbens and ventral
      tegmental area regulate feeding-evoked increases in dopamine release in the
      nucleus accumbens was determined using in vivo brain microdialysis in the rat. In
      some animals a second dialysis probe was implanted in the ventral tegmental area
      ipsilateral to the nucleus accumbens probe. The feeding protocol involved access
      to standard rat chow after 18 h of food deprivation. Under these conditions rats
      began eating approximately 30 s after the introduction of food and consumed 7-8
      g, resulting in a 50% increase in dopamine release. Application of the glutamate
      receptor antagonist kynurenate (1 mM) in the nucleus accumbens potentiated the
      feeding-evoked increase in dopamine release by 80%. Application of the
      metabotropic glutamate receptor agonist trans-1S,3R-1-amino-1,3
      cyclopentanedicarboxylic acid (100 microM) in the nucleus accumbens blocked the
      feeding-evoked increase in dopamine release. Application of a combination of the
      ionotropic glutamate receptor antagonists 2-amino-5-phosphopentanoic acid (200
      microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) through the dialysis
      probe in the ventral tegmental area reduced basal dopamine output in the nucleus
      accumbens by 20% and markedly attenuated (by 70%) the effect of feeding on
      dopamine release. None of the treatments affected the latency to eat or the
      volume of food consumed. These results indicate that glutamatergic afferents to
      the ventral tegmental area mediate feeding-induced increases in dopamine release
      in the nucleus accumbens. In contrast, at physiological concentrations, glutamate
      in the nucleus accumbens appears to decrease dopamine release via actions on
      ionotropic and metabotropic receptors.

PMID- 9027871
TI  - Removal of extracellular calcium after conditioning stimulation disrupts long
      term potentiation in the CA1 region of rat hippocampal slices.
AB  - During a conditioning stimulus, the influx of Ca2+ into neurons appears to be
      crucial for the induction of long-term potentiation at CA1 hippocampal synapses.
      We report here that extracellular Ca2+ is also required for full production of
      long-term potentiation during a critical period following the conditioning
      stimulus. In control slices, removal of extracellular Ca2+ (0 mM Ca2+/10 mM Mg2+)
      for 15 min eliminated synaptic transmission. Following reintroduction of normal
      extracellular solution, synaptic responses recovered fully within 15 min.
      However, removal of extracellular Ca2+ 15-30 min after theta burst stimulation
      significantly decreased the magnitude of long-term potentiation. A time window
      seems to exist for this effect, since either earlier or later Ca2+ removal was
      less effective. The effect of the 0 mM Ca2+/10 mM Mg2+ solution was observed in
      the absence of afferent stimulation, suggesting that evoked synaptic activity is
      not required. Perfusion with an extracellular solution containing Cd2+ (40
      microM), a broad spectrum inhibitor of voltage-dependent Ca2+ channels, or a low
      concentration (50 microM) of Ni2+, which preferentially blocks T-type, low
      voltage-activated Ca2+ channels, also caused a significant decrease in
      potentiation, whereas an inhibitor of L-type, high voltage-activated Ca2+
      channel, nifedipine (20 microM), had no effect. These results suggest that the
      presence of extracellular Ca2+ during a specific period after high-frequency
      synaptic activity is necessary for the maintenance of long-term potentiation, and
      that voltage-gated Ca2+ channels play a role in the stabilization of synaptic
      plasticity.

PMID- 9027872
TI  - In vitro propagation and inducible differentiation of multipotential progenitor
      cells from human fetal brain.
AB  - Central nervous system neurons and glia arise from undifferentiated embryonic
      neuroepithelial cells. Such progenitor cells from the human fetal forebrain can
      be propagated in vitro for extended periods, when grown on non-adhesive
      substrates in medium containing epidermal growth factor and insulin-like growth
      factor-1. These actively-dividing cells can be induced to differentiate into a
      variety of histochemically-characterized neurons and glia consistent with their
      forebrain origin. Electrophysiological recording indicates that differentiated
      neurons derived from these progenitors mature slowly, and display a range of
      glutamate- and GABA-mediated conductances characteristic of normal mammalian
      forebrain neurons. Our observations support a role for these trophic factors in
      normal development of the human brain. The methods described here may provide
      abundant normal, untransformed human forebrain neurons and glia for research and
      therapeutic applications.

PMID- 9027873
TI  - Basic fibroblast growth factor is highly neuroprotective against seizure-induced
      long-term behavioural deficits.
AB  - Basic fibroblast growth factor has been reported to protect neurons of various
      structures from excitotoxic damage. To study the effects of basic fibroblast
      growth factor on seizure-induced brain damage we infused the growth factor into
      the lateral ventricles of 35-day-old rats receiving convulsant dosages of kainic
      acid. Artificial cerebrospinal fluid or basic fibroblast growth factor at dosages
      of 0.5 ng/h or 2.5 ng/h was infused into the lateral ventricle continuously for
      seven days starting two days before and continuing for five days after the
      animals had kainic acid-induced status epilepticus. At age 80 days the animals
      underwent behavioural testing using the water maze, open field, and handling
      tests and at age 95 days were tested for seizure threshold using flurothyl
      inhalation. Neither artificial cerebrospinal fluid or basic fibroblast growth
      factor modified the latency or duration of the acute seizures following kainic
      acid. However, rats infused with 2.5 ng/h, but not 0.5 ng/h of basic fibroblast
      growth factor, had fewer spontaneous recurrent seizures, a higher seizure
      threshold, better performance in the handling, open field and water maze test,
      and less cell loss in the hippocampus when compared to rats receiving artificial
      cerebrospinal fluid or 0.5 ng/h of basic fibroblast growth factor. These results
      show that basic fibroblast growth factor has a dose-related neuroprotective
      effect against seizure-induced long-term behavioural deficits when administered
      by osmotic pump prior to seizure onset. This neuroprotective effect is not
      related to an anticonvulsant effect.

PMID- 9027874
TI  - Nerve growth factor treatment prevents dendritic atrophy and promotes recovery of
      function after cortical injury.
AB  - This study examined the behavioural and anatomical effects of intraventricular
      injections of nerve growth factor in rats with unilateral damage that included
      Zilles' areas Frl, FL, HL, ParI and the anterior portion of Oc2. Nerve growth
      factor-treated lesion rats showed attenuation of behavioural symptoms in measures
      of forelimb function (Whishaw reaching task) and hindlimb function (beam
      traversing task) as well as a measure of spatial navigation (Morris water task).
      Analysis of dendritic arborization using a modified Golgi. Cox procedure also
      showed a complete reversal of lesion-induced atrophy of dendritic fields in
      pyramidal neurons in motor (Zilles' Fr2) and cingulate (Zilles' Cgl) cortex. In
      addition, there was a reversal of a lesion-induced reduction in spine density.
      These results demonstrate that nerve growth factor treatment can facilitate
      functional recovery from cortical injury. This recovery may be mediated by a
      reorganization of intrinsic cortical circuitry that is reflected in changes in
      dendritic arborization and spine density of pyramidal neurons.

PMID- 9027875
TI  - Axonal regeneration of sensory nerves is delayed by continuous intrathecal
      infusion of nerve growth factor.
AB  - While it is well established that nerve growth factor is growth promoting for
      sensory neurons in culture, it is unclear whether it serves such a function in
      vivo. In fact, our previous studies led to the hypothesis that nerve growth
      factor could actually impair axonal regeneration by reducing the neuronal cell
      body response to injury. In the present study, the consequence of continuous
      intrathecal infusion of nerve growth factor on regeneration of sensory neurons
      was examined in rats given a bilateral sciatic nerve crush. Rats received nerve
      growth factor (125 ng/h) as a continuous infusion into the subarachnoid space of
      the lumbar spinal cord via an osmotic minipump (Alzet); controls received
      cytochrome C. At seven or 10 days, the pump was removed and L4 or L5 dorsal root
      ganglion exposed and injected with 50 microCi of (3H)leucine. Animals were killed
      24 h later, the sciatic nerves removed, cut into 3 mm segments and the
      radioactivity in each segment determined by liquid scintillation
      spectrophotometry. Maximal regeneration distances (determined from the front of
      the resultant transport curves) were similarly reduced (by approximately 6 mm) in
      nerve growth factor-infused compared to cytochrome C-infused rats. Thus,
      regeneration rates (determined between eight and 11 days) were unaltered by nerve
      growth factor infusion; regeneration rates from cytochrome C-infused and nerve
      growth factor-infused animals were 2.8 mm/day and 3.1 mm/day, respectively.
      However, nerve growth factor significantly (P < 0.005) increased the delay to
      onset for regeneration by two days. Taken together, the present study
      demonstrates that nerve growth factor delays the onset of regeneration without
      affecting the rate of regeneration. The results implicate the involvement of at
      least two signals in the regulation of axonal regeneration in dorsal root
      ganglion neurons. It is suggested that the loss of nerve growth factor serves as
      an early, induction signal regulating the onset of regeneration and that a
      second, unidentified signal independently serves to maintain regeneration.

PMID- 9027876
TI  - Quantitative and morphometric data indicate precise cellular interactions between
      serotonin terminals and postsynaptic targets in rat substantia nigra.
AB  - We have quantified the density of serotonin axonal varicosities, their synaptic
      incidence and their distribution among potential targets in the pars reticulata
      and pars compacta of the rat substantia nigra. Serotonin axonal varicosities,
      counted at the light microscopic level following in vitro [3H]serotonin uptake
      and autoradiography, amounted to 9 x 10(6)/mm3 in the pars reticulata and 6 x
      10(6)/mm3 in the pars compacta, among the densest serotonin innervations in
      brain. As determined at the electron microscopic level following immunolabelling
      for serotonin, virtually all serotonin varicosities in the pars reticulata and
      50% of those in the pars compacta formed a synapse, essentially with dendrites.
      The combination of serotonin immunocytochemistry with tyrosine hydroxylase
      immunolabelling of dopamine neurons reveals that 20% of the serotonin synaptic
      contacts in the pars reticulata are on dopamine dendrites and 6% are on a type of
      unlabelled dendrite characterized by its peculiarly high cytoplasmic content of
      microtubules. The comparison of the diameter of the dendritic profiles that were
      in synaptic contact with serotonin-immunoreactive varicosities with the diameter
      of all other dendritic profiles of the same type suggests that serotoninergic
      varicosities innervate dopamine dendrites uniformly along their length, whereas
      they tend to contact microtubule-filled dendrites in more proximal regions and
      the other, unidentified dendrites in more distal regions. Furthermore, the size
      of the serotonin-immunoreactive varicosities and of their synaptic junctions is
      significantly smaller on dopamine dendrites and larger on microtubule-filled
      dendrites than on other, unidentified dendrites, indicating that the nature of
      the postsynaptic target is an important determinant of synaptic dimensions. These
      data should help to clarify the role of serotonin in the nigral control of motor
      functions. They indicate that this dense serotonin input to the substantia nigra
      is very precisely organized, acting through both "non-junctional" and
      "junctional" modes of neurotransmission in the pars compacta, which projects to
      the neostriatum and the limbic system, whereas the predominant mode of serotonin
      transmission appears to be of the "junctional" type in the pars reticulata, where
      serotonin can finely control the motor output of the basal ganglia by acting on
      the GABA projection neurons either directly or through the local release of
      dopamine by dopaminergic dendrites. The data also raise the possibility that the
      postsynaptic targets have trophic retrograde influences on serotoninergic
      terminals.

PMID- 9027877
TI  - Effects of graft-derived dopaminergic innervation on the target neurons of patch
      and matrix compartments of the striatum.
AB  - Fetal dopaminergic neurons grafted into the dopamine-depleted striatum have
      previously been shown to normalize neurochemical and behavioural abnormalities.
      However, the extent of graft-induced recovery of striatal compartments, which
      differ in their ontogeny, neurochemical properties and function, is still not
      clear. The striosome and matrix compartments of the striatum provide a segregated
      projection to somatostatin-containing GABAergic neurons of the rostral part of
      the entopeduncular nucleus and somatostatin-negative GABAergic neurons of the
      caudal part of the entopeduncular nucleus, respectively. In the present study,
      preprosomatostatin and glutamate decarboxylase messenger RNA levels in the
      rostral and caudal parts of the entopeduncular nucleus were determined six and 18
      months postgrafting in rats with complete recovery of rotational behaviour
      following apomorphine challenge, and in rats with unilateral 6-hydroxydopamine
      lesions or sham lesions and no grafts. Sections were processed for in situ
      hybridization using 35S-labelled cRNA probes for glutamate decarboxylase (67,000
      mol. wt isoform; GAD67) and preprosomatostatin. Autoradiographs showed a marked
      increase in preprosomatostatin messenger RNA within the ipsilateral
      entopeduncular nucleus in 6-hydroxydopamine-lesioned rats, and a substantially
      lower increase six months postgrafting. At 18 months postgrafting, the
      preprosomatostatin messenger RNA levels were symmetrical within the
      entopeduncular nucleus. Unilateral depletion of striatal dopamine resulted in a
      moderate increase in GAD67 messenger RNA levels within the ipsilateral
      entopeduncular nucleus, along with a substantial decrease in GAD67 levels within
      the contralateral nucleus. By six months postgrafting, the GAD67 levels had
      decreased considerably within the ipsilateral entopeduncular nucleus, while the
      messenger RNA levels had returned to normal within the contralateral nucleus.
      Interestingly, at 18 months postgrafting, the GAD67 levels remained decreased
      within the ipsilateral entopeduncular nucleus and were significantly lower than
      the normal value. The results indicate that fetal nigral grafts placed within the
      dopamine-depleted striatum can restore the neurochemical alterations seen in
      striatal target areas such as the entopeduncular nucleus. This may form the
      neurochemical basis of graft-induced behavioural recovery, as the normalization
      of neurotransmitter messenger RNA levels in the entopeduncular nucleus reflects
      the restoration of overall activity in both direct and indirect striatal output
      pathways. The results also indicate that the graft-derived dopaminergic
      innervation restores the output of both striosome and matrix compartments of the
      striatum. The present results also showed a progressive recovery leading to over
      compensation of neurotransmitter messenger RNA levels following grafting, perhaps
      indicating the importance of feedback regulation of grafted dopaminergic neurons
      by the host.

PMID- 9027878
TI  - Epileptic afterdischarge in the hippocampal-entorhinal system: current source
      density and unit studies.
AB  - The contribution of the various hippocampal regions to the maintenance of
      epileptic activity, induced by stimulation of the perforant path or commissural
      system, was examined in the awake rat. Combination of multiple-site recordings
      with silicon probes, current source density analysis and unit recordings allowed
      for a high spatial resolution of the field events. Following perforant path
      stimulation, seizures began in the dentate gyrus, followed by events in the CA3
      CA1 regions. After commissural stimulation, rhythmic bursts in the CA3-CA1
      circuitry preceded the activation of the dentate gyrus. Correlation of events in
      the different subregions indicated that the sustained rhythmic afterdischarge (2
      6 Hz) could not be explained by a cycle-by-cycle excitation of principal cell
      populations in the hippocampal-entorhinal loop. The primary afterdischarge always
      terminated in the CA1 region, followed by the dentate gyrus, CA3 region and the
      entorhinal cortex. The duration and pattern of the hippocampal afterdischarge was
      essentially unaffected by removal of the entorhinal cortex. The emergence of
      large population spike bursts coincided with a decreased discharge of
      interneurons in both CA1 and hilar regions. The majority of hilar interneurons
      displayed a strong amplitude decrement prior to the onset of population spike
      phase of the afterdischarge. These findings suggest that (i) afterdischarges can
      independently arise in the CA3-CA1 and entorhinal dentate gyrus circuitries, (ii)
      reverberation of excitation in the hippocampal-entorhinal loop is not critical
      for the maintenance of afterdischarges and (iii) decreased activity of the
      interneuronal network may release population bursting of principal cells.

PMID- 9027879
TI  - Development of long-distance efferent projections from fetal hippocampal grafts
      depends upon pathway specificity and graft location in kainate-lesioned adult
      hippocampus.
AB  - Fetal hippocampal cells grafted into the excitotoxically lesioned hippocampus of
      adult rats are capable of extending axonal projections into the host brain. We
      hypothesize that the axonal growth of grafted fetal cells into specific host
      targets, and the establishment of robust long-distance efferent graft
      projections, require placement of fetal cells in close proximity to appropriate
      axon guidance pathways. Intracerebroventricular administration of kainic acid in
      adult rats leads to a specific loss of hippocampal CA3 pyramidal neurons. We
      grafted 5'-bromodeoxyuridine-labeled embryonic day 19 hippocampal cells into
      adult hippocampus at four days post-kainic acid lesion, and quantitatively
      measured the projection of grafted cells into the contralateral hippocampus and
      the septum after three to four months survival using Fluoro-Gold and 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (Dil) tracing. Grafts located
      in or near the degenerated CA3 cell layer exhibited numerous neurons which
      established commissural projections with the contralateral hippocampus. However,
      such projection did not occur in intrahippocampal grafts located away from the
      CA3 cell layer. In contrast, neurons in all grafts established robust projections
      into the septum regardless of location within hippocampus although grafts located
      near the degenerated CA3 cell layer displayed more neurons with such projections.
      Location of grafted cells clearly influences the development of efferent graft
      projections into distant targets in the adult host brain, particularly access to
      axon guidance pathways to facilitate the formation of projections. The
      establishment of robust long-distance commissural projections of fetal
      hippocampal grafts is clearly dependent on their placement in or near the
      degenerated CA3 cell layer, suggesting that appropriate axon guidance pathways
      for commissural pathways are tightly focussed near this cell layer. However, the
      establishment of septal projections of these grafts was not dependent on specific
      location within the CA3 cell layer, suggesting that axonal guidance mechanisms to
      the septum are more diffuse and not limited to the CA3 dendritic layers. The
      results underscore that fetal hippocampal grafts are capable of partly restoring
      lesioned hippocampal circuitry in adult animals when appropriately placed in the
      host hippocampus.

PMID- 9027880
TI  - The ontogeny of NADPH-diaphorase neurons in serum-free striatal cultures
      parallels in vivo development.
AB  - Nitric oxide synthase is co-localized with somatostatin and neuropeptide Y in a
      subpopulation of striatal interneurons that stain selectively for NADPH
      diaphorase. We studied the ontogeny of diaphorase-positive neurons in striatal
      serum-free cultures derived from 15-16-day-old CD1 mice. NADPH-diaphorase
      staining was detected as early as embryological day 18 in vivo and day 5 in
      vitro. Over the next seven days the number of neurons staining for NADPH
      diaphorase increased rapidly and then levelled off at about 0.5-1% of the total
      neuronal population both in vivo and in vitro. The cultured diaphorase neurons
      were also similar to their in vivo counterparts in terms of morphology and
      dendritic branching. Striatal neurons expressing NADPH-diaphorase exhibit similar
      ontogeny, morphology and neurochemical characteristics in vivo and in serum-free
      primary neuronal cultures. The culture system may represent a useful model for
      studying this important subgroup of striatal neurons.

PMID- 9027881
TI  - The role of nitric oxide in focally-evoked limbic seizures.
AB  - The deep rostral piriform cortex contains a site (area tempestas) in which focal
      application of picomole amounts of bicuculline, a GABA antagonist, triggers
      limbic motor seizures which are dependent upon activation of both N-methyl-D
      aspartate and alpha-amino-3-hydroxy-5-methyloxole-4-proprionate subtypes of
      glutamate receptors. In the present study we determined whether nitric oxide can
      influence the local modulation of seizure initiation by bicuculline. Nitric oxide
      and the nitric oxide precursor L-arginine, alone or in combination with low doses
      of bicuculline were focally administered into the area tempestas of rats. While
      nitric oxide alone had no significant convulsant effect, L-arginine alone (30-240
      nmol) induced brief myoclonic episodes. Nitric oxide (0.7 nmol) and L-arginine
      (30 nmol) markedly potentiated the seizures evoked by a low dose of bicuculline.
      The effect of L-arginine was prevented by focal pretreatment with an inhibitor of
      nitric oxide synthesis, N-nitro-L-arginine methyl ester. However, N-nitro-L
      arginine methyl ester did not attenuate the convulsant effect of bicuculline or
      kainate alone when focally administered into area tempestas. The data demonstrate
      that exogenously applied nitric oxide or its precursors can enhance seizure
      triggering activity. However, the data also indicate that L-arginine-nitric oxide
      pathway does not normally contribute to seizure expression from area tempestas,
      as N-nitro-L-arginine methyl ester alone did not attenuate focally-evoked
      seizures.

PMID- 9027882
TI  - The morphology and connections of neurons in the gasping centre of adult rats.
AB  - Neuronal activities in the intermediate reticular nucleus and adjacent lateral
      tegmental field are critical for the neurogenesis of the ventilatory pattern of
      gasping. We report herein the anatomical features of these neurons, their axonal
      projections and the location of neurons providing afferent inputs. These
      neuroanatomical evaluations were performed by iontophoretic injection of the
      tracer Neurobiotin into the region of the intermediate reticular nucleus of the
      rat. At the site of injection, neurons having soma of 30-50 microns were filled.
      Labelled axons and terminals were observed in ipsilateral regions which contain
      neurons having established functions in the control of ventilatory activity.
      These regions include the nucleus ambiguous and motor nuclei of the hypoglossal
      and facial nerves. In addition, axonal projections extended to the contralateral
      region of the intermediate reticular nucleus. From this contralateral region,
      retrograde tracing revealed projections to the site of injection. Similarly, many
      ipsilateral regions which received axonal terminals from the region of the
      intermediate reticular nucleus had reciprocal projections to this region. These
      anatomical results support the physiological observation that the neurogenesis of
      gasping involves a synchronized activation of diverse components of the brainstem
      ventilatory control system.

PMID- 9027884
TI  - Interaction of the movement-dependent, extrafusal and fusimotor after-effects in
      the firing of the primary spindle endings.
AB  - The after-effects of the firing of the primary spindle endings were studied in
      ankle extensor muscles of cats under Nembutal anesthesia. The activities of 27
      primary endings of the muscle spindles from mm. soleus, plantaris, and
      gastrocnemius have been analysed in various combinations of fusimotor and
      extrafusal stimulation and application of the mechanostimulation to the spindle
      bearing muscle. Short-term simulation of static gamma-axons evoked a post
      stimulation increase in the spindle ending firing, which can be recorded under
      both isometric and isotonic conditions on applying a weak extrafusal stimulation
      or without it. The movement-dependent after-effects were tested with a double
      trapezoid pattern of muscle length (or load) changes. The after-effects consisted
      of the difference of firing rates at the same values of muscle length (or load)
      with opposite direction of movement to the steady states; these uncertainties
      were also present during constant stimulation of static gamma-axons. The rate
      difference showed a tendency to a certain decrease with stimulation rate
      increment. For diapason of the stimulation rates up to 125 impulses/s a small
      negative correlation (r = -0.61) between the firing rate differences and the
      gamma-stimulation rate has been registered in the population of primary endings
      tested under length servo-control conditions. Using a frequency-modulated
      intrafusal stimulation, a clockwise hysteresis dependence of the spindle firing
      rate upon stimulation rate was demonstrated. The pronounced after-effects were
      shown to exist for steady rates of stimulation: the discharge rates were always
      higher after stimulation rate increase and lower after its decrease. Fusimotor
      after-effects were effectively destroyed by both the extrafusal stimulation and
      the cyclic length (load) changes evoked lengthening-shortening movements of the
      muscle. The results obtained can be considered as evidence for a hypothesis that
      history-dependent behavior of muscle spindles is mainly connected with hysteresis
      of the intrafusal muscle fibers and the whole spindle bearing muscle.

PMID- 9027883
TI  - Neurokinin A in rat renal afferent neurons and in nerve fibres within smooth
      muscle and epithelium of rat and guinea-pig renal pelvis.
AB  - Neurokinin A-like immunoreactivity of dorsal root ganglion neurons innervating
      the kidney were studied with retrograde tracing of FluoroGold dye applied to the
      cut renal nerves. The proportions and sizes of renal afferent neurons with
      neurokinin A-like immunoreactivity were quantified in T9-L2 dorsal root ganglia
      from five rats. Of 240 renal afferent neuronal somata examined, 26 +/- 3%
      (S.E.M.) showed neurokinin A-like immunoreactivity. Compared with the overall
      size distribution of renal afferent neurons, those staining for neurokinin A were
      mostly small-sized neurons with a few medium-sized neurons. All somata with
      neurokinin A-like immunoreactivity were neurofilament-poor as judged by labelling
      with an anti-neurofilament antibody, RT97, and it is therefore likely that they
      had unmyelinated fibres. To examine the sites to which the renal afferent fibres
      with neurokinin A might project, sections of rat and guinea-pig kidney and upper
      ureter were examined. Fibres with neurokinin A-like immunoreactivity were found
      beneath and within the transitional epithelium lining the inner surface of the
      pelvis, and within the smooth muscle layer beneath the transitional epithelium.
      Epithelial innervation was found only in regions with underlying smooth muscle
      and loose connective tissue, and not in sites where the epithelium was closely
      applied to the renal parenchyma. The network of fibres was most dense towards the
      pelvo-uretic junction. Fibres with neurokinin A-like immunoreactivity were not
      seen beneath or within the cuboidal/columnar epithelium covering the papilla
      within the renal pelvis. Furthermore, only very few fibres with neurokinin A were
      observed penetrating the transitional epithelium of the upper ureter in both rat
      and guinea-pig. The distribution of fibres labelled with antibodies to substance
      P and calcitonin gene-related peptide in the renal pelvis was similar to that for
      fibres with neurokinin A-like immuno-reactivity, although a few fibres penetrated
      further into the fornices than fibres with neurokinin-A-like immunoreactivity.
      Thus, many afferent fibres in the renal pelvis may contain neurokinin A as well
      as substance P and calcitonin gene-related peptide. These fibres may be the
      source of the neurokinin A, substance P and calcitonin gene-related peptide which
      can be released by topical capsaicin treatment. In addition they may be the
      mechano- and chemo-receptive fibres in the renal pelvis that are known to play
      important roles in renal haemodynamics. The intra-epithelial position of some of
      these fibres in the epithelial layer suggests a possible chemosensory or
      osmosensory role.

PMID- 9027885
TI  - [Functional neurosurgery with an implantable and programmable pulse-generator:
      control of involuntary movement disorders].

PMID- 9027886
TI  - [Surgical approaches to spinal arteriovenous malformations: anatomy and operative
      methods].

PMID- 9027887
TI  - [Treatment of metastatic brain tumors from lung cancer: analysis of performance
      status between treatment methods].
AB  - Retrospective analysis was performed in 280 patients; 112 surgical cases and 168
      non-surgical cases to determine which of three treatments, alone or in
      combination provides more prolonged improvement of performance status (PS:
      Karnofsky score) in patients with metastatic brain tumors from lung cancer. The
      treatments under scrutiny were surgical removal of metastatic brain tumor (S),
      radiation therapy (R) and chemotherapy (C). KS in the group treated with S or C
      showed a significantly better result than that in the non-S group or non-C group
      during the two-year observation period. However, R group showed no significant
      improvement in KS compared to that in the non-C group during the two-year period.
      During the first year after admission, two subgroups of S plus R and R alone
      showed most rapid decrease in KS. However, subgroups of S plus C and S plus R and
      C showed better results than other subgroups. In analyzing the changes in KS over
      the short period from admission to one month after treatment had been completed,
      the non-S group showed a significant decrease in KS, while the S group showed a
      slight increase in mean KS. The subgroup of R alone showed the greatest decrease
      in KS. Thus, retrospective analysis showed that surgical removal of a metastatic
      brain tumor led to improved KS for a short period and chemotherapy was useful in
      prolonging the duration of better Q.O.L.

PMID- 9027888
TI  - [Practical localization of the central sulcus using a video display during
      surgery by cortical somatosensory evoked potentials and how to discern precentral
      P20 and central P25].
AB  - In patients with lesions around the central sulcus, cortical surface
      somatosensory evoked potentials (SEPs) have been applied for the purpose of
      localization of the central sulcus based on the polarity inversion of postcentral
      N20 to precentral P20 across the central sulcus. We have intraoperatively
      monitored SEPs to infer the location of the central sulcus in 16 cases since
      December 1988. Intraoperative localization of the central sulcus has been most
      useful in patients with frontal lobe gliomas in which the localization of the
      central sulcus enables the surgeon to extensively resect tumor without
      postoperative motor weakness. The localization of the central sulcus, however,
      might be misjudged by using the polarity inversion criterion alone, because
      central P25 following N20 and P20 complicates SEP waveforms. It is significant
      that P25, which is recorded also posterior to the central sulcus, is discerned
      from the precentral P20. In order to solve this matter, we regarded only the
      positivity in SEP waveforms having the identical peak latency to that of N20 as
      the precentral P20. Positive potentials having a later peak latency than that of
      N20 are the superposition of P20 and P25, and might also be recorded posterior to
      the central sulcus. For the observation of the polarity inversion of N20 to P20
      across the central sulcus, a multi-channel SEP should be recorded using a sheet
      of silicone rubber embedded in a 16-electrode array consisting of a 4 by 4 grid.
      We projected the exposed cortical surface on the video display through the
      microscope apparatus and marked the locations of the recording electrodes on the
      video display. This enabled the location of the recording electrodes to
      correspond easily and precisely to the cortical surface. Our reliable and simple
      method of intraoperative localization of the central sulcus by cortical SEPs
      monitoring is presented in a practical case.

PMID- 9027889
TI  - [The clinical analysis of pediatric meningioma: 5 cases].
AB  - Five cases of pediatric meningioma were reported with special emphasis on the
      clinical features. These cases consisted of three boys and two girls between
      eight and fifteen years old. Two were falx meningioma, two were suprasellar, and
      one was petroclival. One falx meningioma was associated with Neurofibromatosis
      II, and a suprasellar case had no dural attachment, but had cystic component
      after recurrence. Histologically, there were three meningothelial, one
      transitional, and one fibrous meningioma. No malignant meningioma was found among
      any of the cases. Two cases received postoperative irradiation and had no
      recurrence. A falx meningioma with Neurofibromatosis II and a suprasellar with no
      dural attachment had evidence of recurrence. The latter suffered from severe
      neurological deficits after reoperation. It was suggested that irradiation
      against residual tumor should be considered. However, total removal should be
      carried out in pediatric cases of meningioma. The authors concluded that our
      cases had features intermediate between adult meningiomas and pediatric
      meningiomas because the majority of cases were senior children.

PMID- 9027890
TI  - [Histopathological examinations of dural arteriovenous malformations of posterior
      fossa].
AB  - Two cases of dural arteriovenous malformation (DAVM) of the posterior fossa were
      presented and a histopathological examination was described. After embolization
      of the feeding arteries, DAVMs of the posterior fossa were removed with the
      adjacent sinus. Serial sections of the surgical specimens showed an abnormal mass
      with dilated, tortuous vessels of varying diameters in the sinus wall, and
      partially hyalinized connective tissue around the vessels. The elastic lamina of
      the sinus wall was interrupted and a mass of abnormal vessels developed into the
      subintimal layer of the sinus. Fistulas, about 200 microns in diameter, were
      formed between arterialized dural veins and dural arteries which had obvious
      internal elastic lamina. An opening of the fistula of the abnormal vessel, 25
      microns in diameter, to the sinus lumen was also seen. No stage of organized
      thrombus could be seen in the sinus lumen. These findings strongly suggested that
      physiologically existing arteriovenous fistulas within the dura mater, which have
      been reported by Kerber et al, had developed due to many factors which increase
      intracranial pressure. They protruded into the sinus lumen in such a way that it
      could cause stenosis or obstruction of the sinus. In conclusion it can be said
      that an obstructive lesion of dural sinus is considered of itself to be DAVM in
      most cases and sinus thrombosis is the result of the DAVM.

PMID- 9027891
TI  - [Surgical management of extracranial internal carotid artery aneurysms].
AB  - Aneurysms of the extracranial internal carotid artery are rare but may present as
      a mass, with ischemic symptoms, or with fatal hemorrhage. We operated on
      aneurysms in four patients, two males and two females, whose ages ranged from 47
      to 57 years. While a lot of etiological factors for the aneurysms have been known
      to include trauma, vascular dysplasia, infection or surgery using patch graft for
      carotid endarterectomy, three aneurysms in our series were atherosclerotic and
      one was spontaneously dissecting. One patient had focal neurological deficit due
      to embolism, two presented with a growing cervical mass, and one was symptom
      free. The aneurysm was located proximal below the angle of the mandible in three
      patients and was distal above the angle in one. All patients were found able to
      tolerate test occlusion of the internal carotid before surgery. The aneurysm was
      trapped in one case (case 1) and was encased by vascular prosthesis in another
      (case 4). In the other two cases, arterial reconstruction after aneurysmal
      resection was carried out. In one case out of the two, the aneurysm was located
      at the level of 2nd cervical vertebral body (case 2). Vertical mandibular
      osteotomy was performed posteriorly to the exit of the inferior alveolar nerve
      from the bone, which gave a good view of the upper third of the internal carotid
      artery and facilitated primary end-to-end anastomosis. In the other case in which
      there was a dilated distal carotid artery and multiple aneurysms at the basilar
      and bilateral vertebral arteries (case 3), an extracranial-intracranial (EC-IC)
      saphenous vein bypass was inserted so as not to increase the hemodynamic stress
      in the posterior circulation. Except for a transient lower cranial nerve palsy in
      one case (case 2), there were no incidences of morbidity or death. Magnetic
      resonance angiography (MRA), Doppler ultrasonography or three-dimensional CT
      angiography (3-D-CT-A) was found useful in evaluating the change of aneurysmal
      size. It is essential in surgery for an internal carotid artery aneurysm to
      choose an appropriate approach characterized by its size and location. It may be
      important in cases with associated vascular lesions to estimate the potential
      hemodynamic change that might be induced by aneurysmal surgery.

PMID- 9027892
TI  - [Giant thrombosed fusiform aneurysm at the branch of the middle cerebral artery
      presenting with intramural hemorrhage: a case report].
AB  - We report a rare case of a giant thrombosed fusiform aneurysm at the branch of
      left middle cerebral artery presenting with intramural hemorrhage of the
      aneurysm. A twenty-year-old man with familial and past history of migraine
      presented sudden temporalgia on August 13, 1995. Computed tomography (CT) scan on
      the day of the first attack revealed a well delineated high density area at the
      left Sylvian fissure, 2.5cm in diameter. Angiogram showed avascular area
      corresponding to the lesion, but no visualization of the aneurysm. On October 18,
      this patient presented sudden temporalgia again. CT scan on the day of the second
      attack indicated new intramural hemorrhage and surgery was performed on October
      31. No evidence of subarachnoid hemorrhage was shown during the operation, and
      the lesion was proven to be a thrombosed fusiform aneurysm at the branch of the
      middle cerebral artery. The parent artery was clipped at both proximal and distal
      sides of the aneurysm, and the aneurysm was totally removed with success.
      Histological finding further supported the idea that the attacks mentioned were
      due to intramural hemorrhage of the thrombosed aneurysm. Postoperative course was
      uneventful and the patient was discharged without any neurological deficit.
      Intramural hemorrhage of a giant fusiform aneurysm is relatively rare, only
      reported in several autopsy cases. Furthermore, we failed to discover any
      comparable cases of giant fusiform aneurysm presenting symptoms directly caused
      by intramural hemorrhage of the aneurysm.

PMID- 9027893
TI  - [A case of chronic subdural hematoma associated with idiopathic thrombocytopenic
      purpura (ITP)].
AB  - We reported a case of ITP associated with chronic subdural hematoma. A 51-year
      old female was admitted to our hospital with left frontal pain on November 18,
      1995. CT and MRI examinations revealed a left chronic subdural hematoma.
      Peripheral platelet count showed thrombocytopenia, 5,000/mm3. She was treated
      preoperatively by administration of steroids, a large dose of immunoglobulin and
      transfusion of platelet. Five days after admission, platelet count had elevated
      to 199,000/mm3, and evacuation of the hematoma through a burr hole under local
      anesthesia was performed successfully. No troubles were observed during and after
      surgical procedure. Intracerebral hemorrhages associated with coagulopathy are
      rather common, but only 6 cases of ITP associated with chronic subdural hematoma
      have been reported. The characteristic clinical features and treatment of these 6
      cases including our own case was noted. The cases of patients less than 40 years
      old were usually treated by emergency operation with transfusion of platelet
      because of severe neurological deficits. However, in the cases of patients over
      40 years old treated by elected operation after administration of steroids, a
      large dose of immunoglobulin and transfusion of platelet did not give rise to
      severe neurological deficits. Therefore, we emphasize that the treatment against
      thrombocytopenia should be recommended taking the age of patients into
      consideration.

PMID- 9027894
TI  - [A case of olfactory neuroblastoma with intracranial, intraorbital extension and
      multiple metastases].
AB  - A 51-year-old man presented with headache, vomiting and exophthalmus.
      Neurological examination revealed anosmia, papilledema, decrease in visual
      acuity, and disability in ocular movement. MRI showed a huge mass which occupied
      the whole nasal cavity and compressed the frontal lobe upwards and the eyes
      laterally. CT revealed an extensive bony destruction of the frontal base and
      bilateral orbits. The mass was biopsied transnasally, and was histologically
      diagnosed as olfactory neuroblastoma. It was highly radiosensitive and
      disappeared with a local irradiation of 40 Gy. Three months later the patient
      complained of a pain radiating from the neck to the right arm. MRI demonstrated a
      metastasis at the vertebral body of C5. Local irradiation of 30 Gy was performed.
      The metastatic lesion was removed, and a bone graft taken from the iliac bone was
      transplanted via an anterior cervical approach. Three weeks later, however, a
      hard mass appeared in the right of his neck and was surgically removed. By
      histological examination, it was also identified as a metastatic neuroblastoma to
      the cervical lymph node. A week after the removal of the cervical metastatic
      lesion, the metastasis extended rapidly to the left cervical and the bilateral
      hilar lymph nodes of the lungs. Chemotherapy was performed with a total doses of
      800mg of cyclophosphamide, 1.5mg of vincristine, 40mg of pirarubicin, and 80mg of
      cisplatin. The lesions disappeared within 7 days. However, the patient died from
      disseminated intravascular coagulation 10 months after the onset. Olfactory
      neuroblastoma is usually an intranasal neoplasm, but it rarely extends
      intracranially and intraorbitally as is shown in our case. Basically, olfactory
      neuroblastoma is a relatively slow-growing tumor though it has a tendency to
      develop local recurrences over long periods even after aggressive primary
      treatment, and accompanied with distant metastases. However, our patient showed a
      very short survival time. Invasive extension and multiple metastases occurred
      during a short period, followed by disseminated intravascular coagulation.
      Combined chemotherapy at the initial treatment may be recommended in such an
      extensive case.

PMID- 9027895
TI  - [Lymphocytic infundibulo-hypophysitis with diabetes insipidus as a new clinical
      entity: a case report and review of the literature].
AB  - In 1992, we reported a lymphocytic adenohypophysitis (LIH) (Neurol Med Chir). We
      considered this case unusual in that the case was that of a menopausal female and
      that it was accompanied with diabetes insipidus as classical lymphocytic
      adenohypohysitis (LAH). Subsequently, Ahmed reported two cases which presented a
      similar pathological manifestation, except for necrosis, as did our case and
      named them "necrotizing infundibulo-hypophysitis." Recently we encountered
      another similar case, which is reported hereunder. A female, 34 years of age, had
      suffered from headache, polyuria, and amenorrhea. CT scan showed a pituitary
      mass, and pituitary tumor was surgically removed transcranially at a local
      hospital. The pathological examination revealed the findings of chronic
      inflammation and necrosis. One month after the operation, however, she was an in
      patient again under the suspicion of meningitis for fever and, when antibiotic
      therapy at the local hospital resulted in no improvement, she was referred to our
      hospital. Endocrinological studies showed low FSH, LH, ACTH and plasma cortisol
      level. Antibodies of serum to RNP, Sm, mitochondria, nucleus, AChR, and DNA were
      all negative. Because of an intrasellar mass with suprasellar extension on MRI,
      transsphenoidal operation was conducted four months after the initial operation.
      The pathological examination revealed the infiltration of lymphocytes, plasma
      cells, and foamy macrophages, and necrosis. After this operation, the headache
      was cured and the patient was discharged. Two months subsequent to the second
      operation, headache recurred and temporal upper quadrantic anopsia was noted. An
      enlarged tumor was found, but prednisolone worked to cure the pain and the visual
      field defect was found to have been remedied. The patient's diabetes insipidus is
      presently persisting, and she still relies on the use of desmopressin acetate and
      is still in need of cortisol replacement therapy. Including our cases, ten cases
      of lymphocytic hypophysitis, not related to pregnancy or delivery but with
      diabetes insipidus, have been reported. Several clinical and anatomical features
      distinguish these 10 cases from classical LAH. The classical LAH was
      predominantly related to pregnancy or delivery. However 6 of 10 cases were male
      in LIH. LAH related to pregnancy or delivery does not accompany diabetes
      insipidus, but all reported cases of LIH had a diabetes insipidus. Visual field
      and/or ocular movement disturbance are LAH's chief complaints (15 out of 25
      cases) but visual field disturbance seldom occurs in LIH (1 out of 10 cases).
      Hypopituitarism is more serious in LAH, and 4 cases became fatal from an adrenal
      crisis. Anatomically, inflammatory change of LIH is located anterior and
      posterior to the pituitary gland and extends to the pituitary stalk and, at
      times, hypothalamus. On the other hand, LAH relates to pregnancy or delivery, the
      inflammatory change localizes to the adenohypophysis. Ahmed emphasized necrosis,
      while necrosis was not a prominent histological finding in LIH. Necrosis was
      noted only in 3 of 10 cases. To be stressed, rather, are the inflammatory changes
      seen on the neurohypophysis and the pituitary stalk, together with the
      characteristic diabetes insipidus. We believe, in view of the above, that what
      Ahmed named necrotizing infundibulo-hypophysitis should be named "LIH with
      diabetes insipidus." Whereas differential diagnosis is necessary between this
      said new disorder and the conventional LAH, we advocate that the latter, which is
      related to pregnancy or parturition but is free from neurohypophysitis be
      identified as "LAH related to pregnancy or delivery." With respect to treatment,
      steroid therapy is essential. If the symptoms do not improve, a transsphenoidal
      operation for diagnosis (LIH and LAH) and decompression (the case of LAH with
      visual or external ocular movement disturbance) is advisable. However, extensive
      surgery is not recommended, because per

PMID- 9027896
TI  - [A Rathke's cleft cyst with a moving mass in the cyst].
AB  - We reported a case of Rathke's cleft cyst (RCC) with a moving mass in the cyst. A
      fifty-eight-year-old woman complaining of headache was admitted to our hospital.
      She suffered from hyponatremia, hypothalamic hypopituitarism, but did not show
      any neurological deficits, nor visual field nor visual acuity disturbance. MRI
      revealed an intrasellar cyst including a mass shadow and the cyst did not
      compress the hypothalamus. Interestingly, this mass moved gradually from the
      floor to the posterior wall of the sella turcica according to changes in position
      from standing to supine. We operated to remove the cyst partially by
      transsphenoidal approach. Xanthochromic fluid flowed out from the cyst. In
      addition, a brownish globular mass, 6 mm in diameter, existed within the cyst
      without connection to the surrounding tissue. Pathological findings showed that
      the capsule consisted of cuboid epithelium and was partially stratified, which
      confirmed the diagnosis of Rathke's cleft cyst. However, the mass was
      homogeneously stained with H.E., containing no cells, cellular debris, nor
      connective tissue. PAS stain was negative. Though we could not clarify the
      material in the cyst, this case is very rarely one of Rathke's cleft cyst. This
      case demonstrated the possibility of hypothalamic hypopituitarism in spite of the
      cyst being almost located in the sella turcica. We surmise that a cyst near the
      stalk of the pituitary gland, even if it is not so large, might compress the
      portal vein, and thus the function of hypothalamus-pituitary axis.

PMID- 9027897
TI  - [A case of a surgically treated extracranial internal carotid artery saccular
      aneurysm].
AB  - Extracranial internal carotid artery aneurysm is rare. Most cases are due to
      spontaneous or traumatic dissection of the cervical internal carotid artery. Here
      we report a case of surgically treated extracranial internal carotid artery (ICA)
      aneurysm. A 74-year-old man noticed a pulsatile mass just below the left
      mandibular angle. Intravenous digital subtraction angiography revealed multiple
      aneurysms in the systemic arteries, including the aortic arch, abdominal aorta
      and left extracranial ICA. It was decided to treat the aneurysms of the aortic
      arch and of the abdominal aorta conservatively. Cerebral angiography, however,
      showed a saccular aneurysm which projected latero-posteriorly at the C2 level of
      the left extracranial ICA. Although the patient had no previous ischemic event,
      we decided to treat this aneurysm surgically in view of the risk of cerebral
      ischemia caused by intraaneurysmal thrombus formation or rupture of the aneurysm
      by neck injury. The operation was performed under mild hypothermal general
      anesthesia. Electroencephalography was carried out during the operation. A skin
      incison was made from the anterior border of the sternocleidomastoid muscle to
      the pretragal region to expose the parotid gland. This skin incision, elevation
      of the parotid gland and division of the digastric muscle were useful for
      exposing the distal portion of the extracranial ICA. After trapping of the
      aneurysm, it was punctured and collapsed by aspiration and the dome was excised
      at its neck. The ICA was then reconstructed by suturing the cut neck of the
      aneurysm. Patency of the ICA was confirmed by postoperative angiography. The
      postoperative course was smooth except for hoarseness, which was caused by damage
      to a minor branch of the vagus nerve during exposure of the aneurysmal dome.

PMID- 9027898
TI  - [Neuropathology of AIDS: opportunistic infections and HIV encephalopathy].

PMID- 9027899
TI  - [AIDS-related primary central nervous system lymphoma].

PMID- 9027900
TI  - [Neurological manifestations associated with HIV-1 infection].

PMID- 9027902
TI  - [Neuropathological study on progression of the limbic degeneration in senile
      dementia of Alzheimer type].
AB  - Neuropathological study on the limbic lesion of 33 autopsy cases with senile
      dementia of Alzheimer type (SDAT) showed as follows. 1) The entorhinal cortex was
      more atrophied than the hippocampus. 2) Neuronal loss was found in the 2nd and
      3rd layers of the entorhinal cortex, irrespective of the different numbers of
      senile plaques and neurofibrillary tangles (NFTs). 3) Fibrillary gliosis occurred
      in the stratum lacunosum of the hippocampus, irrespective of the different
      degrees of neuronal loss in the stratum pyramidale of the hippocampus. 4) The
      prosubiculum showed gliosis disproportional to neuronal loss. 5) The degree of
      fibrillary gliosis in the stratum lacunosum of the hippocampus and in the
      prosubiculum was proportional to that of the entorhinal cortical degeneration. 6)
      The shape of the hippocampus of the cases with SDAT was different from that in
      the cases with anoxic encephalopathy in which neuronal loss in the CA1 occurred
      primarily: 7) Distribution pattern of the lesion in the hippocampus of SDAT cases
      was almost the same as that found in the cases with infarct in the collateral
      sulcus involving the entorhinal cortex. It is assumed that the hippocampal
      atrophy is a primary degeneration attributable to appearance of senile plaques
      and NFTs. However, our present observations and previous report (Neurosci Lett
      184: 141-144 1995) suggest that degeneration of the entorhinal cortex and its
      efferent fibres (perforant pathway) plays a considerable part of role in
      development of the hippocampal atrophy. The present study could contribute to
      understanding of progression of the limbic lesion in SDAT.

PMID- 9027903
TI  - [Localization of epileptogenic foci and visualization of propagating process in
      the seizure discharges using crosscorrelation analysis].
AB  - Electrocorticogram (ECoG) of intractable focal epilepsy was analyzed using AR
      model, wavelet analysis and crosscorrelation analysis. The sequential 3
      dimensional visualization technique of phase shift maps was developed to localize
      the epileptic foci and to study their propagation process. The crosscorrelation
      of the epileptic discharges was calculated between the electrodes in every unit
      of time, to get the phase shift. More than two epileptogenic foci were localized
      and two kinds of propagating process were shown. These findings suggest that two
      kinds of mechanism might work in development of epileptic discharges, and our
      newly developed visualization technique is useful to investigate the
      epileptogenesis etiology.

PMID- 9027904
TI  - [Evaluation of various somatosensory stimulations for functional MRI].
AB  - The aim of this functional magnetic resonance imaging (fMRI) study was to test
      detectability of activated area using various somatosensory stimulations. The
      following stimulations were performed in normal volunteers: regular or irregular
      electrical median nerve stimulation (n = 5, each), tactile stimulation to the
      palm and fingers (n = 8), pain stimulation to the index finger (n = 5) or to the
      palm and fingers (n = 5). fMRI was acquired with a spoiled gradient echo sequence
      at 1.5 T. Detectability of activated area was the highest when the pain
      stimulation was applied to the palm and fingers (80%). A successful rate for the
      tactile stimulation was 25%, and the other stimulations failed to demonstrate any
      activation. When successful, the highest signal activation on fMRI was seen on a
      sulcus, which presumably arose from a vein. The sulcus was defined as the central
      sulcus by somatosensory evoked field using a median nerve stimulation. Our study
      indicates that the pain stimulation to the palm and fingers may be a choice for
      the sensory fMRI.

PMID- 9027901
TI  - [Virology on AIDS and AIDS dementia complex].

PMID- 9027905
TI  - [Expression of interferon-alpha mRNA in human brain tissues].
AB  - The localization of mRNA of interferon-alpha (IFNA21) was examined in human brain
      tissues from neurologically normal, Parkinson's and Alzheimer's disease (AD)
      cases, using an in situ hybridization method. In all cases, signals for the mRNA
      of IFNA21 were detected in the white matter microglial cells. In AD brains, a few
      neurons in the parietal lobe were intensely labeled. These results suggest that
      one type of IFN-alpha protein is constitutively expressed in white matter
      microglial cells, and that expression of IFN-alpha in neuronal cells may play
      some role in AD pathology.

PMID- 9027906
TI  - [Hemifacial spasm].

PMID- 9027907
TI  - [Prolonged antegrade amnesia due to left anterior thalamic infarct, and SPECT
      findings].
AB  - A 60-year-old right-handed man developed disorientation, antegrade amnesia and
      transient mild clouding of consciousness. The antegrade amnesia persisted for
      more than one year after its onset. T2-weighted MR images showed high signal
      intensity in the left anteromedial thalamus. 99mTc-HM-PAO SPECT revealed
      decreased uptake in the left frontal and temporal lobes. These SPECT findings
      were still observed a year later. These findings suggest that functional
      involvement of the frontal and temporal lobe connections with the dorsomedial
      nucleus, anterior nucleus, and the mamillothalamic tract in the anteromedial part
      of thalamus were responsible for the prolonged antegrade amnesia. We think that
      SPECT findings are important for evaluating the outcome of thalamic amnesia.

PMID- 9027908
TI  - [A case of infected subdural hematoma complicating chronic subdural hematoma in a
      healthy adult man].
AB  - The authors report a case of so-called "infected subdural hematoma" as a
      complication of chronic subdural hematoma. The patient was a 55-year-old man who
      had sustained a small laceration of the forehead in a traffic accident on March
      29, 1995. No fractures were detected on skull roentgenograms, and general and
      neurological examinations failed to reveal any abnormal findings. In early August
      1995, the patient began to experience headaches, and on August 5 he developed a
      fever of 38 degrees C. On August 8 he suffered a left motor seizure and was
      admitted to our hospital. Laboratory studies revealed a peripheral leukocyte
      count of 10,800/mm3 and a C-reactive protein level of 18.1 mg/dl. Computed
      tomography scans showed a thick right fronto-parietal subdural low density mass
      and a thin left frontal subdural low density mass. An emergency operation was
      performed via a single right fronto-parietal burr hole. A chronic subdural
      hematoma containing slightly yellowish, bloody, purulent fluid was found beneath
      an outer membrane. The hematoma was irrigated with physiological saline
      containing antibiotics, and a drain was inserted into the subdural space. A
      subdural membrane was also present on the left but it contained no pus.
      Aggressive antibiotic therapy was performed, and the patient was discharged
      without any neurological deficit. Histologically the membrane was determined to
      be the outer membrane of a typical chronic subdural hematoma. Enterococcus
      faecalis, which has rarely been reported to cause infection of the central
      nervous system, was detected in a bacterial culture of the pus. Systemic
      investigation showed no evidence of otorhinologic or other focal infection. The
      above clinical findings suggested that hematogenous seeding of a chronic subdural
      hematoma had occurred in this patient. Subdural empyema arising from hematogenous
      seeding to a pre-existing subdural hematoma by an infection is very rare, but
      this type of complication must be kept in mind not only in the elderly, infants,
      and compromised hosts, but in patients without complications as well.

PMID- 9027909
TI  - [Transarterial platinum coil embolization for direct carotid-cavernous fistula].
AB  - Two cases of direct carotid-cavernous fistula (CCF) were treated by transarterial
      platinum coil embolization (TACE) following unsuccessful transarterial balloon
      embolization (TABE). Case 1 was a 47-year-old man who complained of pulsatile
      left exophthalmos, chemosis and bruit. Left carotid angiograms showed a CCF with
      anterior, posterior and cortical venous drainage. Near total obliteration of the
      CCF was achieved by TABE, but it showed recurrence in the next morning. At this
      time, left carotid angiograms showed a CCF which drained only into the cortical
      veins via the enlarged sphenoparietal sinus. Because of high risk of intracranial
      hemorrhage, TACE was performed immediately. The result was successful. Case 2 was
      an 82-year-old woman who suffered from traumatic subarachnoid hemorrhage. First
      right carotid angiograms showed a small CCF which drained only into the inferior
      petrosal sinus. Right exophthalmos, swelling of the eyelids, severe eye pain and
      bruit appeared gradually. The second right CAG performed three months after the
      head trauma showed markedly dilated superior ophthalmic vein which was the new
      main draining root of the CCF. Because of progressive symptoms, TACE was
      performed immediately after the angiography, which proved successful. Direct CCFs
      must be treated aggressively because they don't cure by spontaneous obstruction
      of fistula. Although TABE is the first choice for direct CCF, complete occlusion
      of CCF in difficult in some cases. Those cases have; 1) small fistula of CCF for
      balloon insertion, 2) large fistula for occlusion by balloons, 3) not enough
      space for inserting a balloon after recurrence of CCF, and 4) sharp objects (bone
      fracture fragments, foreign objects) may puncture the balloon. If TABE couldn't
      provide successful treatments, TACE should be considered as an alternative
      treatment for direct CCF after angiography without delay because it is less
      complex compared with TABE.

PMID- 9027910
TI  - [A 70-year-old man with a progressive gait disturbance and gaze palsy].
AB  - We report a 70-year-old man with progressive gait disturbance and gaze palsy. The
      patient was well until summer of 1991 when he was 66-year-old, when he noted a
      gradual onset of difficulty in gait and looking downward. He was evaluated in our
      hospital in May, 1994 when he was 69-year-old. On admission, he was alert but
      markedly demented with disorientation and memory loss. Constructional apraxia and
      dressing apraxia were noted. He had difficulty in gaze to all directions; he
      could move his eyes only 20% of the normal range. Oculocephalic response was
      retained. He had small voice and some dysphagia. Other cranial nerves were
      unremarkable. He could not walk unsupported. Marked retropulsion was noted in
      which he would fell down spontaneously upon standing unless supported. Moderate
      to marked rigidity was noted in the neck, trunk, and in the legs, however, in the
      upper extremities, rigidity was only mild. No tremor was noted. Deep reflexes
      were symmetrically exaggerated with ankle clonus bilaterally. Plantar response
      was flexor. Sensation was intact. Routine laboratory tests were unremarkable,
      however, his cranial MRI showed moderate to marked fronto-temporal atrophy and
      moderate midbrain and pontine tegmental atrophy. The third ventricle was markedly
      dilated. He was discharged for out patient care, however, his dysphagia had
      become progressively worse, and he suffered from frequent bouts of pneumonia. He
      was admitted to our service on October 17, 1994. His neurologic examination was
      essentially similar except that he showed more advanced dementia. He was still
      able to stand with support. Gastrostomy was placed on October 25. Post-operative
      course was unremarkable. He was discharged on November 1. His motor disturbance
      showed gradual deterioration, and by the May of 1995, he became bed-ridden, and
      was admitted to another hospital on May 30, 1995. He was almost totally unable to
      move his eyes, but oculocephalic response was still elicited. Marked truncal and
      limb rigidity were noted. He vomited coffee-ground substance on October 31, 1995,
      and developed hypotension. The subsequent course was complicated by pneumonia and
      he expired on November 24. The patient was discussed in a neurological CPC.
      Majority of the participants thought that the patient had progressive
      supranuclear palsy, but some participants thought that the patient had
      corticobasal degeneration because cortical atrophy was so marked. Post mortem
      examination revealed atrophy of the frontal and parietal lobe. The brain stem was
      atrophic particularly in the tegmental area including the midbrain. The
      substantia nigra showed marked neuronal loss and globose type neurofibrillary
      tangles in the remaining neurons. The neurons in the locus coeruleus was well
      retained, however neurofibrillary tangles were seen. In addition, the cerebellar
      dentate nucleus, the inferior olivary nucleus, and the internal globus pallidus
      showed marked neuronal loss and neurofibrillary degeneration. In the frontal
      cortex, although macroscopic examination showed some atrophy, microscopic
      examination failed to show neuronal loss or gliosis. The pathologic findings were
      consistent with the diagnosis of progressive supranuclear palsy.

PMID- 9027911
TI  - Noninvasive first-trimester screening for fetal aneuploidy.
AB  - We reviewed all studies concerning noninvasive first trimester screening for
      fetal aneuploidy obtained from a MEDLINE search through June 1996 with additional
      sources identified through cross-referencing. Three screening and diagnostic
      modalities are of potential application in noninvasive first trimester testing
      for fetal aneuploidy: ultrasound, maternal biochemical markers, and analysis of
      fetal cells retrieved from maternal sources. Sensitivities of the sonographic
      finding of nuchal translucency thickness in combination with maternal age for
      trisomy 21, performed between 10 and 14 weeks of gestation in experienced hands,
      and maternal biochemical markers independently may be as high as 86 percent and
      60 percent, respectively. Sensitivity, specificity, and predictive values of
      these diagnostic modalities alone, in combination with each other, or in
      conjunction with other predisposing factors such as maternal age, in large low
      risk populations have not currently been established. Analysis of fetal cells
      retrieved from maternal sources, although more complex, may offer definitive
      noninvasive prenatal diagnosis yet is not currently available in clinical
      practice. We conclude that noninvasive first trimester screening for fetal
      aneuploidy modalities including sonographic examination for nuchal translucency
      thickness and maternal biochemical markers, is feasible. Clinical feasibility;
      and all-encompassing clinical management paradigms of these and other early
      noninvasive first trimester screening methods for fetal aneuploidy, are not yet
      available.

PMID- 9027912
TI  - Hydrops fetalis: recent advances.
AB  - Hydrops fetalis is a morbid condition caused by a wide variety of fetal,
      placental, and maternal diseases. Mortality is high and depends on the
      gestational age at the time of occurrence and underlying etiology. Although the
      condition was described more than 300 years ago, recent advances in obstetric
      ultrasound, prenatal diagnostics have made it possible to differentiate various
      etiologies involved. It is also possible to treat some of these fetuses
      prenatally. In utero medical and surgical therapy is presently done in some
      centers. However, the majority of cases diagnosed remain untreatable. Early
      diagnosis of untreatable cases allows parents to make informed choices about
      subsequent management. Recent advances are covered in this review.

PMID- 9027913
TI  - Effectiveness of interventions to prevent or treat impaired fetal growth.
AB  - This is an overview of 126 randomized controlled trials (RCTs) evaluating 36
      prenatal interventions to prevent or treat impaired fetal growth (IFG). Results
      are based on systematic reviews including the meta-analyses of these RCTs. Most
      of the prenatal interventions do not show any significant effects on short-term
      perinatal outcomes. There are, however, a few interventions likely to be
      beneficial: smoking cessation, antimalarial chemoprophylaxis in primigravidae,
      and balanced protein/energy supplementation. Others merit further research: zinc,
      folate, and magnesium supplementation during gestation. Appropriate combinations
      of interventions should be a priority for evaluation because it is unlikely that
      a single intervention will reduce a multicausal outcome like IFG that is so
      dependent on socioeconomic disparities. Of concern is the discrepancy between the
      importance given in the epidemiological and clinical literature to the problem of
      IFG and the methodological quality and sample size of the RCTs conducted for the
      evaluation of preventive or treatment modalities.

PMID- 9027919
TI  - The deeper lesson of Alhazen.

PMID- 9027920
TI  - Descriptions of visual phenomena from Aristotle to Wheatstone.
AB  - A history of the observational era of vision is presented through selected
      descriptions of phenomena by natural philosophers from Aristotle to Wheatstone.
      The descriptions are listed under the headings of optics, colour, subjective
      visual phenomena, motion perception, eye movements, binocular vision, and space
      perception.

PMID- 9027921
TI  - On the ancient history of the direction of the motion aftereffect.
AB  - Scientists agree that Aristotle in his Parva Naturalia was the first to report a
      visual illusion known as the motion aftereffect (MAE). But there is less
      consensus as to who was the first to report the direction of the MAE. According
      to some, Aristotle only described the phenomenon without saying anything about
      its direction. Others have defended the position that Aristotle did report a
      direction, but the wrong one. Therefore, it has been suggested that Lucretius in
      his poem De Rerum Natura was the first to report the correct direction of the
      MAE. In this paper it is shown why and how it can be inferred that Aristotle did
      not write about the direction of the MAE, only about its occurrence. It is also
      argued that it is indeed likely that Lucretius was the first person to report the
      direction of the MAE. However, this is not as obvious as it might appear at first
      sight.

PMID- 9027922
TI  - Ptolemy's contributions to the geometry of binocular vision.
AB  - Ptolemy's Optics which was written in about the year 150 AD contains an account
      of the geometry of binocular vision which has been almost totally neglected in
      the vision literature. An English translation of the relevant passages from the
      Latin text in Lejeune (1956) is presented together with commentaries and a brief
      introduction.

PMID- 9027923
TI  - Alhazen's neglected discoveries of visual phenomena.
AB  - The first three books of the Book of Optics written by Alhazen in Cairo in the
      eleventh century were translated into English by A I Sabra in 1989. Book I deals
      with optics, the structure of the eye, image formation in the eye, and with the
      visual pathways. This book inspired all other books on optics from the thirteenth
      to the seventeenth century and formed the basis upon which Kepler solved the
      problem of image formation. However, Alhazen's work contained in Books II and III
      has been almost totally ignored. These two books contain an account of hundreds
      of observations and experiments carried out by Alhazen on a broad range of topics
      which are now studied under the heading of visual perception. He clearly
      enunciated many of the fundamental principles which are credited to scientists
      living in the last two hundred years, including a theory of unconscious
      inference; the law of equal innervation of the eye muscles; the principles of
      binocular direction; constancy of size, shape, and colour; induced visual motion;
      the vertical horopter; the fusional range of binocular disparity; and many
      others.

PMID- 9027924
TI  - Why Goethe rejected Newton's theory of light.
AB  - Observations that he himself had made persuaded Goethe to reject Newton's theory
      of light and to put forward an alternative theory of the colour phenomena seen
      with a prism. Duck has argued that Goethe's attack on Newton's theory rested on
      valid experimental observations that appeared to present a difficulty for
      Newton's theory but to support his own views on colour. Duck has also proposed
      that these observations may be accounted for as an instance of the Bezold-Brucke
      phenomenon. It is argued here that this explanation is invalid and that two other
      features of colour processing can explain Goethe's observations.

PMID- 9027925
TI  - Bergmann on visual resolution. 1857.

PMID- 9027926
TI  - A gem from the past: Pleikart Stumpf's (1911) anticipation of the aperture
      problem, Reichardt detectors, and perceived motion loss at equiluminance.

PMID- 9027927
TI  - Motion perception: a modern view of Wertheimer's 1912 monograph.
AB  - Max Wertheimer's 1912 monograph on apparent motion is a seminal contribution to
      the study of visual motion, but its actual contents are not widely known. This
      article attempts to clarify what the monograph did and did not contribute,
      emphasizing links between Wertheimer's principal findings and the results of
      subsequent investigations of motion perception, including currently active lines
      of research. The topics discussed include Wertheimer's experimental tests of
      explanations for apparent motion; his work with motion phenomena that lie between
      succession and optimum motion; his studies of the influence of attention on
      motion; explorations of various forms of hysteresis and motion transparency; and
      Wertheimer's work with a motion-blind patient.

PMID- 9027928
TI  - Temporal lobe dysfunction and correlation of regional cerebral blood flow
      abnormalities with psychopathology in schizophrenia and major depression--a study
      with single photon emission computed tomography.
AB  - Studies of regional cerebral blood flow in both schizophrenic and depressed
      patients have yielded contradictory findings. Single photon emission computed
      tomography (SPECT) was used to compare brain-perfusion patterns in 17 patients
      with schizophrenia and 12 patients with major depression and to evaluate the
      relationship of the findings to psychopathology. The images were analyzed both
      visually and quantitatively. Twelve of the 17 schizophrenic patients and 8 of the
      12 depressed patients showed a pathological blood flow pattern. Hypoperfusion of
      the left temporal lobe was observed in seven of the schizophrenic and five of the
      depressed patients. Five of the schizophrenic patients also had a hypoperfusion
      of the left frontal lobe. Separation of both diagnostic cohorts in two subgroups
      with pathological and normal cerebral blood flow patterns revealed significantly
      higher levels of symptomatology in the group with hypoperfusion in the SPECT
      image. The analysis of different cerebral regions revealed statistically
      significant temporal hypoperfusion was significantly related to positive symptoms
      in schizophrenia. Our data suggest that left-sided temporal lobe dysfunction is
      related both to schizophrenia and major depression. The localization of
      hypoperfusion seems to be associated with the type of psychopathology (positive
      vs. negative symptoms in schizophrenia). Thus, the results support the model of
      paralimbic and prefrontal dysfunction in both diseases.

PMID- 9027929
TI  - Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using
      [18F]altanserin and positron emission tomographic imaging.
AB  - We used [18F]altanserin and positron emission tomography (PET) to image serotonin
      5-HT2A receptors in humans. The highest [18F]altanserin uptake is found in the
      cerebral cortex, with specific-to-nonspecific binding ratios varying from 0.53 to
      1.91 in humans between 24 and 48 years of age. In all neocortical regions
      studied, [18F]altanserin uptake correlates negatively with age. No correlations
      were found between age and uptake in the cerebellum, the regional cerebral blood
      flow, or the time course of metabolization of [18F]altanserin. The reduction in
      cerebral 5-HT2A receptor binding thus directly reflects the loss of specific 5
      HT2A receptors with age.

PMID- 9027930
TI  - Striatal dopamine-2 receptor occupancy in psychotic patients treated with
      risperidone.
AB  - Seventeen psychiatric patients (11 with schizophrenia, 5 with other psychotic
      disorders, and 1 with obsessive-compulsive disorder) were examined by single
      photon emission computed tomography with 123I-iodobenzamide (IBZM) as tracer.
      Patients were treated with risperidone in two different dosage groups (3 mg and 8
      mg) and haloperidol (10-20 mg) and compared with eight healthy control subjects.
      There was a statistically significant difference in basal ganglia/frontal cortex
      ratios of IBZM binding between controls and all treatment groups. A statistically
      significant difference was also found concerning these ratios and percentage of
      dopamine D2 receptor occupancy rates between the treatment groups with lowest
      ratios and highest percentage of D2 receptor occupancy in the group of patients
      treated with haloperidol, followed by the group treated with 8 mg of risperidone
      and the group treated with 3 mg of risperidone.

PMID- 9027931
TI  - Quantitative EEG correlates of panic disorder.
AB  - Quantitative analysis of electroencephalographic (EEG) signals recorded from
      multiple scalp sites was used to compare panic disorder patients (n = 34) with
      normal healthy controls. Patients exhibited greater overall absolute power in the
      delta, theta, and alpha frequency bands and less relative power in the beta band.
      Discriminant analysis of absolute power indices correctly classified 75% of the
      subjects, while relative power indices exhibited a 69% correct-classification
      rate. Absolute delta and theta power were positively correlated with observer
      ratings of anxiety, while relative beta power was related to self-ratings of
      anxiety.

PMID- 9027932
TI  - High frequency of EEG and MRI brain abnormalities in panic disorder.
AB  - The frequency and quality of brain abnormalities in panic disorder (PD) were
      assessed with magnetic resonance imaging (MRI). The use of electroencephalography
      (EEG) to detect PD patients with a high probability of morphologic brain
      abnormalities was also explored. Consecutive PD patients (n = 120) were screened
      with routine EEG examinations and were divided into the following subgroups on
      the basis of their EEG findings: patients with non-epileptic EEG abnormalities
      (EEG-A group, n = 28), matched patients with normal EEG results (EEG-N group, n =
      28) and matched healthy controls (n = 28). PD patients showed a higher than
      expected rate of non-epileptic EEG abnormalities (29.2%; 35 of 120). EEG
      screening was effective in identifying patients with a high probability of
      morphologic brain abnormalities. MRI abnormalities were found in 60.7% of the EEG
      A patients, 17.9% of the EEG-N patients, and only 3.6% of the controls. A high
      frequency of septo-hippocampal abnormalities was found. Further research should
      focus on attempts to subtype PD on the basis of neuroanatomic and functional
      brain abnormalities.

PMID- 9027933
TI  - Magnetic resonance imaging changes in putamen nuclei iron content and
      distribution in normal subjects.
AB  - To study patterns of iron deposition in the putamen in aging, we reviewed brain
      magnetic resonance imaging (MRI) scans of 56 normal subjects. We developed the
      Signal Hypointensity in the Putamen (SHIP) Scale, a semiquantitative measure, to
      evaluate putamen nuclei for extent of iron deposition relative to the globus
      pallidus. The SHIP score was highly reliable (kappa = 0.76) and significantly
      correlated with age (P < 0.0001). We found that age-related iron deposition in
      putamen nuclei follows a characteristic pattern along a posterolateral-to
      anteromedial gradient. This gradient may be related to the microvasculature of
      the putamen. Other studies are needed to replicate our findings in patients with
      affective and other neuropsychiatric disorders and to clarify the
      pathophysiological mechanisms that govern these changes.

PMID- 9027934
TI  - Adverse effect of treatment gaps in the outcome of radiotherapy for laryngeal
      cancer.
AB  - BACKGROUND AND PURPOSE: A correlation has been demonstrated between unplanned
      prolongation of radiotherapy and increased local relapse. This review was
      performed to assess the importance of overall time on the outcome of curative
      radiotherapy of larynx cancer. MATERIALS AND METHODS: Retrospective analysis was
      performed of 383 patients with laryngeal cancer managed by elective radiotherapy
      between 1976-1988 in the Department of Clinical Oncology, University of
      Edinburgh, Western General Hospital, Edinburgh All cancers were confirmed
      histologically to be squamous cell carcinomas. All subjects received radiotherapy
      in 20 daily fractions (except Saturdays and Sundays), employing individual beam
      direction techniques and computer dose distribution calculations. Main outcome
      measures were complete resolution of the cancer in the irradiated volume; local
      relapse; survival and cause-specific survival rates. RESULTS: Radiotherapy was
      completed without any unplanned interruption (28 +/- 2 days) in 230/383 (60%) of
      patients. A statistically significant two-fold increase in local relapse rates
      was observed when treatment was given in 31 days or more. There also was a
      statistically significant four-fold increase in laryngeal cancer deaths when the
      treatment time exceeded 30 days. CONCLUSIONS: In patients with laryngeal cancer,
      accelerated repopulation of cancer cells probably occurs after the start of
      radiotherapy. When the overall treatment time is 4 weeks or less, gaps at
      weekends are not detrimental. However, long holiday periods or gaps in treatment
      longer than 4 days increase the risk of laryngeal cancer relapse and cancer
      related mortality. Significant gaps in treatment should be avoided. If treatment
      has to be prolonged, additional radiation dose should be prescribed to compensate
      for increased tumour cell proliferation.

PMID- 9027936
TI  - Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies
      following acoustic neuroma radiosurgery.
AB  - PURPOSE AND OBJECTIVE: To define the relationships between dose and tumor
      diameter for the risks of developing trigeminal, facial, and acoustic
      neuropathies after acoustic neuroma radiosurgery, a large single-institution
      experience was analyzed. MATERIALS AND METHODS: Two hundred and thirty-eight
      patients with unilateral acoustic neuromas who underwent Gamma knife radiosurgery
      between 1987-1994 with 6-91 months of follow-up (median 30 months) were studied.
      Minimum tumor doses were 12-20 Gy (median 15 Gy). Transverse tumor diameter
      varied from 0.3-5.5 cm (median 2.1 cm). The relationships of dose and diameter to
      the development of cranial neuropathies were delineated by multivariate logistic
      regression. RESULTS: The development of post-radiosurgery neuropathies affecting
      cranial nerves V, VII, and VIII were correlated with minimum tumor dose and
      transverse tumor diameter (P < 0.01 for all except Dmin for VIII where P = 0.10).
      A comparison of the dose-diameter response curves showed the acoustic nerve to be
      the most sensitive to doses of 12-16 Gy and the facial nerve to be the least
      sensitive. CONCLUSION: The risks of developing trigeminal, facial, and acoustic
      neuropathies following acoustic neuroma radiosurgery can be predicted from the
      transverse tumor diameter and the minimum tumor dose using models constructed
      from data presently available.

PMID- 9027935
TI  - Soft tissue sarcoma of the extremity. Limb salvage after failure of combined
      conservative therapy.
AB  - PURPOSE: To assess the results of salvage therapy using surgery alone or surgery
      and re-irradiation for patients with locally recurrent extremity soft tissue
      sarcoma (STS) following conservative surgery and radiotherapy. MATERIALS AND
      METHODS: 25 patients with locally recurrent STS after conservative surgery and
      irradiation were assessed between 1990 and 1995. Two patients with concurrent
      systemic relapse were treated palliatively. Seven patients were not candidates
      for conservative re-excision and underwent amputation, 11 patients underwent
      conservative resection without irradiation. Seven of these patients relapsed, and
      five went on to receive combined conservative surgery and re-irradiation. A
      further five patients initially received combined retreatment, for a total of ten
      patients treated with combined conservative surgery and re-irradiation. Six of
      these ten patients were treated with brachytherapy alone, one with brachytherapy
      and external beam therapy, and three with external beam therapy alone. The median
      retreatment dose was 49.5 Gy (range 35-65 Gy), and the median cumulative soft
      tissue dose was 100 Gy (range 93-120 Gy). RESULTS: The median follow-up from the
      most recent treatment is 24 months (range 7-42 months). At the last follow-up 14
      patients are alive and disease free; two are alive with local disease and four
      with systemic disease, and five are dead of disease. Overall local control is
      19/23 (91%). The local control for patients treated with conservative excision
      without irradiation is 4/11 (36%) and for conservative excision with re
      irradiation 10/10 (100%). Six (60%) of these patients experienced significant
      post-irradiation would-healing complications, but three have recovered fully.
      Functional scores for the entire treated group are significantly lower after
      treatment, as are those for patients undergoing combined surgery and re
      irradiation, but 70% of those treated with conservative surgery and re
      irradiation and a good or excellent post-treatment functional score. CONCLUSIONS:
      Combined conservative surgery and re-irradiation provided superior local control
      to local re-excision alone and a functional outcome superior to amputation.
      Combined treatment with re-irradiation should be considered the primary salvage
      therapy for patients who fail combined therapy and who are suitable for
      conservative re-excision. Systemic relapse is a significant problem, and optimal
      therapy should minimize the risk of local relapse after the initial therapy.
      Eighteen patients (72%) had a history of intralesional excision as their initial
      intervention, and suggests that inappropriate initial management is a risk factor
      for relapse after combined conservative therapy. Improvements in therapy must
      include the appropriate education of the primary care physicians.

PMID- 9027937
TI  - Narrow photon beam dosimetry for linear accelerator radiosurgery.
AB  - The dosimetric characteristics of linear accelerator radiosurgery for 10-MV X-ray
      were measured. Measurement of the relative output factor and tissue maximum ratio
      with a microchamber produced results equivalent to those of measurement with X
      ray film. The 80% isodose level width measured with the microchamber was
      significantly smaller than that measured with the X-ray film. For the measurement
      of relative output factor and tissue maximum ratio, a microchamber seems to be
      the more appropriate choice. X-Ray film was found to be suitable for beam profile
      measurement.

PMID- 9027938
TI  - Effect of carbogen breathing on tumour microregional blood flow in humans.
AB  - BACKGROUND AND PURPOSE: Carbogen is currently being re-evaluated as a
      radiosensitiser. It acts primarily by increasing tissue pO2, although there is
      evidence to suggest that enhanced tumour blood flow may also be a component of
      its action. MATERIALS AND METHODS: Ten tumours in eight patients with advanced
      malignant disease were studied. Up to six microprobes, each with an estimated
      sampling volume of 10(-2) mm3, were inserted into the tumours. Ten min of
      baseline readings were taken prior to a 10 min carbogen (95% O2/5% CO2) breathing
      period, measurements were continued for a further 10 min. RESULTS: The results
      show that in 34 microregions analysed no overall change in tumour perfusion was
      seen with carbogen breathing. Individual tumour analysis demonstrated variation
      in response between patients to carbogen-after 6 min of carbogen four tumours
      showed an increase in blood flow by more than 10% of the pre-breathing value, two
      a decrease and four no change. The magnitude of change was small, with only two
      tumours fluctuating by more than 25%. CONCLUSIONS: These findings confirm the
      presence of transient fluctuations in microregional blood flow in human tumours
      but suggest that the radiosensitising action of carbogen lies primarily in its
      effect on increasing the oxygen capacity of blood. This supports the addition of
      agents such as nicotinamide with carbogen in order to overcome both diffusion and
      perfusion limited hypoxia.

PMID- 9027939
TI  - Clearance of parenchymal tumors following radiotherapy: analysis of
      hepatocellular carcinomas treated by proton beams.
AB  - Clearance of a parenchymal tumor following radiotherapy was determined by using
      follow-up CT scans of 18 hepatocellular carcinoma tumors treated with focused
      proton beams. Regression analysis of the daily decrement (DD) and the diameter
      (D) of a tumor mass in each CT observation interval, DD = a*Db, showed that the
      exponent b was 3.0 or larger in early periods and 2.0 or smaller in late periods.
      This suggests that the clearance depends initially on the tumor volume,
      subsequently on the tumor surface area, and then it becomes much more moderate,
      possibly due to radiation damage to the parenchymal tissues.

PMID- 9027940
TI  - Enrichment of tumor cells for cell kinetic analysis in human tumor biopsies using
      cytokeratin gating.
AB  - PURPOSE: To determine the feasibility of using cytokeratin antibodies to
      distinguish normal and malignant cells in human tumors using flow cytometry. The
      goal was ultimately to increase the accuracy of cell kinetic measurements on
      human tumor biopsies. MATERIAL AND METHODS: A panel of four antibodies was
      screened on a series of 48 tumors from two centres; 22 head and neck tumors
      (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried
      out by immunohistochemistry on frozen sections to test intensity of staining and
      the fraction of cytokeratin-positive tumor cells. The antibody showing the most
      positive staining was then used for flow cytometry on the same tumor. RESULTS:
      The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best
      results with immunohistochemical staining, being positive in over 95% of tumors.
      Good cell suspensions for DNA flow cytometry could be made from frozen material
      by a mechanical method, whereas enzymatic methods with trypsin or collagenase
      were judged failures in almost all cases. From fresh material, both collagenase
      and trypsin produced good suspensions for flow cytometry, although the fraction
      of tumor cells, judged by proportion aneuploid cells, was markedly higher for
      trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow
      cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells
      was then tested by measuring the fraction of aneuploid cells (the presumed
      malignant population) of cytokeratin-positive cells versus all cells. An
      enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment,
      tumor cells only) was then calculated. The average enrichment was 0.60 for head
      and neck tumors and 0.59 for esophagus tumors. CONCLUSIONS: We conclude that this
      method can substantially enrich the proportion of tumor cells in biopsies from
      carcinomas. Application of this method could significantly enhance accuracy of
      tumor cell kinetic measurements.

PMID- 9027941
TI  - Optimal interfraction interval to minimize small bowel radiation injury in
      treatment regimens with two fractions per day: an experimental study in a rat
      model.
AB  - BACKGROUND: Normal tissue damage in fractionated radiotherapy is influenced by a
      number of factors including sublethal damage repair and cellular proliferation.
      The therapeutic benefit of regimens with multiple fractions per day may thus be
      offset by increased normal tissue injury if there is insufficient time between
      daily fractions. We examined the influence of interfraction interval on radiation
      injury of the intestine, an organ at significant risk during treatment of
      abdominal and pelvic tumors. METHODS: A total of 150 male rats were
      orchiectomized, and a functionally intact loop of small bowel was sutured to the
      inside of the scrotum. The intestine within this 'artificial hernia' was
      irradiated twice daily for 9 days with 2.8 Gy fractions at intervals of 0, 2, 4,
      6, or 8 h. Animals were observed for development of radiation-induced intestinal
      complications and euthanized at either 2 weeks and 26 weeks for subsequent
      histopathologic examination of irradiated and shielded intestine. RESULTS:
      Increasing the interfraction interval from 0 to 6 h was associated with a
      statistically significant reduction in intestinal complications (from 53% to 0%,
      P < 0.001), and in Radiation Injury Score (RIS) (from 10 to 6, P < 0.01) in long
      term observed animals. Extending the interfraction interval to 8 h did not confer
      additional benefit. CONCLUSION: An interfraction interval of 6 h minimizes the
      risk of chronic radiation enteropathy in this rat model.

PMID- 9027943
TI  - Comparative treatment planning between proton and X-ray therapy in locally
      advanced rectal cancer.
AB  - BACKGROUND AND PURPOSE: Conformal treatment planning with megavoltage X-rays and
      protons for medically inoperable patients with a large rectal cancer has been
      studied in an attempt to determine if there are advantages of using protons
      instead of X-rays. MATERIAL AND METHODS: Three dose plans were made for each of
      the six patients: one proton plan, including three beams covering the primary
      tumour and adjacent lymph nodes and three boost beams covering the primary
      tumour: one X-ray plan, eight beams including a boost with four beams and one
      mixed plan with four X-ray beams and a boost with three proton beams. A three
      dimensional treatment-planning systems, TMS, was used. The evaluation of the
      different plans was made by applying the biological models TCP and NTCP on the
      dose distributions in terms of dose-volume histograms. RESULTS: The comparison
      shows advantages of using protons instead of X-rays for all six patients, but in
      three of them, the advantage is only marginal. The dose-limiting organ at risk is
      the small bowel, but the proton plan and the mixed plan also spare the bladder
      and the femoral heads better. At 5% NTCP in any risk organ, the calculated mean
      TCP value for the six patients is increased by 14%-units with the proton plan and
      8%-units with the mixed plan compared to X-rays only. CONCLUSIONS: Proton beam
      therapy has potential advantages when treating medically inoperable patients with
      a large rectal cancer over conventional X-ray therapy. Since the benefits are
      comparatively small, although clinically worthwhile, large randomised studies are
      needed.

PMID- 9027942
TI  - Combined preoperative irradiation and direct postoperative 5-fluorouracil without
      negative effects on early anastomotic healing in the rat colon.
AB  - BACKGROUND AND PURPOSE: Preoperative irradiation with direct postoperative
      chemotherapy could benefit patients undergoing surgery for colorectal cancer.
      This study was designed to examine, in an experimental model, if such treatment
      is feasible without detrimental effects on early anastomotic healing. MATERIAL
      AND METHODS: A colonic segment was irradiated (25 Gy) in 3 groups (n = 10 each)
      of male Wistar rats. After 5 days, a colonic resection was performed with
      anastomotic construction; only the distal limb consisted of irradiated bowel.
      Postoperatively, animals received daily intraperitoneal 5-fluorouracil (5-FU,
      group I/CH: 17.5 mg/kg; group I/CL: 12.5 mg/kg) or saline (group I). Three
      additional groups were treated similarly, but with sham-irradiation: CH, CL and
      C, respectively. All rats were killed 7 days postoperatively. Parameters measured
      were: weight, serum albumin and protein, and anastomotic bursting pressure,
      breaking strength and hydroxyproline content. RESULTS: Body weight was diminished
      significantly in rats receiving chemotherapy. Serum albumin and protein was
      significantly lower in irradiated groups. At sacrifice, 40% of I/CH rats had
      functional rectal stenosis. The average bursting pressure (P = 0.0005) and the
      average breaking strength (P = 0.012) were only reduced significantly in the CH
      group. The anastomotic hydroxyproline content was significantly higher in the
      I/CH and I/CL groups vs. the control group. CONCLUSION: High-dose direct
      postoperative 5-FU leads to reduced anastomotic strength. Although the
      combination of preoperative irradiation (25 Gy) and direct postoperative high
      dose 5-FU does not reduce early anastomotic strength, some stenosis may occur.
      The combination of preoperative irradiation and low-dose 5-FU has no such effect.

PMID- 9027944
TI  - Comparison of the kidney dose between supine and prone position for pelvic and
      periaortic irradiation.
AB  - We compared the doses received by the kidney in supine and prone positions for
      pelvic and periaortic irradiation. Kidney locations were verified by CT images
      taken with patients in the same position as during the treatment. Due to the
      shift of the kidney anteriorly during prone position, treatment in supine
      position delivered a much lower dose to most of the kidney than treatment in the
      prone position. Therefore, for periaortic irradiation treatment, the supine
      position should be considered to minimize the dose to the kidneys, even though
      the prone position with a belly board can reduce the dose to the small bowel.

PMID- 9027945
TI  - Beam flatness perturbation effects of a perforated thermoplastic immobilization
      device on 6 and 12 MeV electron beams.
AB  - PURPOSE: Perforated thermoplastic masks are widely used in radiotherapy of head
      and neck malignancies. They provide for patient immobilization and increase setup
      reproducibility. Some oncology treatment centers cut mask portals (windows) for
      the beam to pass through; for those centers that do not, the mask affects beam
      fluence. The extent to which beam flatness is altered by such a mask is
      investigated. MATERIALS AND METHODS: The effects of perforated thermoplastic on 6
      MeV and 12 MeV electron beams was described in terms of optical density
      differences in a comparative film study. RESULTS: Variations of beam flatness
      were documented of up to 11.8% at 5 mm depth for 6 MeV, and 8.1% for 12 MeV
      electrons. The depth at which this effect may be considered insignificant (mean
      optical density differences < 2%) is approximately 10 mm for both beam energies.
      CONCLUSIONS: For clinical situations where the target volume is superficial, some
      consideration should be given to beam inhomogeneity caused by the mask.

PMID- 9027946
TI  - Characterization of dose distribution in radiation therapy plans.
AB  - As a method of considering only significant radiation doses to different tissues,
      the ICRU Report 50 recommends taking the dose given to a significant tissue
      volume (minimum diameter greater then 15 mm) instead of choosing a single,
      potentially insignificant, voxel value. In order to find this significant volume,
      we have adapted an emission imaging analysis method to radiation therapy
      planning. The resulting method finds and characterizes the dose distribution in
      the volumes of interest in a way that includes spatial arrangement. The data can
      be used to signal significant hot or cold volumes in the dose plan and to score
      the plans based on significant dose to the tissues.

PMID- 9027947
TI  - Classification, etiology, and considerations of outcome in acute liver failure.
AB  - Clinical descriptions of fulminant hepatic failure as originally reported, along
      with the subgroups of subfulminant and late onset hepatic failure identified
      later, are considered in relation to the proposed new classification of
      hyperacute, acute, and subacute liver failure. This reflects different clinical
      patterns of illness, etiology, and most importantly, prognosis. In addition to
      the defining state of encephalopathy and other manifestations directly related to
      the severe derangement in function and structure of the liver, the constellation
      of clinical symptoms and signs in acute liver failure (ALF) includes, to varying
      degrees, those of multiorgan failure. The latter develops because of tissue
      hypoxia from microcirculatory changes consequent on endotoxemia, and activation
      of macrophages and release of cytokines as a result of secondary bacteria
      infection due to an early failure of host defenses to infection in ALF.
      Paracetamol overdose-the commonest cause of acute liver failure in the United
      Kingdom-is increasing in frequency in other Western countries, but fulminant
      viral hepatitis is the most frequent etiology worldwide. Marked geographical
      variations are seen in the frequency with which the viral types A to E are
      implicated. Whereas hepatitis C is the major cause of ALF in Japan and the Far
      East, fulminant hepatitis C is seen rarely in America and European countries
      where most series show that in about one third of cases of presumed viral ALF, no
      specific agent can be identified. Over the past 10 years, the survival of those
      with grade 3 to 4 encephalopathy has shown a steady rise as a result of
      improvements in medical care, quite apart from the introduction and now
      widespread availability of transplantation for the treatment of this condition.
      As shown by a number of groups, a variety of different hematologic, biochemical,
      and clinical features can be used as predictive indices of the likely outcome and
      in determining the approach to treatment.

PMID- 9027948
TI  - Fulminant hepatic failure: pediatric aspects.
AB  - In children, fulminant hepatic failure is a rare multisystem disorder in which
      severe impairment of liver function, with or without encephalopathy, occurs in
      association with hepatocellular necrosis in a patient with no recognized
      underlying chronic liver disease. Recognized etiologies include infections,
      toxins, metabolic disorders, infiltrative diseases, autoimmune hepatitis,
      ischemic or irradiation damage; a proportion of cases are cryptogenic. The
      diagnosis of the cause is essential to institute lifesaving medical treatment,
      decide if transplantation is indicated, and offer genetic counseling. The maximum
      International Normalized Ratio *(INR) reached during the course of the illness is
      the most sensitive predictor of outcome, mortality being 86% with an INR > or =
      4, and 27% with an INR < 4 in our own series. Prognosis is worse in children
      younger than 2 years. Thus, urgent transplantation should be considered when the
      INR reaches 4, particularly in very young children. Survival after
      transplantation is 60% to 68%. Children with fulminant hepatic failure must be
      treated in specialized centers with facilities for liver transplantation.

PMID- 9027949
TI  - Mechanisms of liver damage.
AB  - The liver is implicated in many processes, and its failure induces severe
      consequences for metabolism, immune response, detoxification and antimicrobial
      defenses. The mechanisms involved in liver injury are complex and interactive,
      and can be artificially separated as chemical and immune injuries. The
      biochemical mechanisms concern various chemicals that are detoxified in the liver
      via cytochrome P-450 and conjugation. Toxic metabolites may alter plasma
      membrane, mitochondria, intracellular ion homeostasis, or degratative enzyme
      activity. Immune mechanisms involve cell cooperation, and are mediated by
      cytokines, nitric oxide, and complement. Pathologic apoptosis is potentially an
      important mechanism of acute liver injury. Specific attention is paid here to the
      more frequent causes of acute liver failure: hypoxia/reoxygenation, liver
      congestion, acetaminophen poisoning, posttransplant acute liver rejection, severe
      sepsis, viral hepatitis, and alcoholic liver disease. Knowledge of the intimate
      mechanisms of liver injury at the cellular level may lead to adaptation of
      therapeutic strategies that will prevent end-stage liver failure.

PMID- 9027950
TI  - Management of acute liver failure.
AB  - Acute liver failure (ALF) constitutes a medical emergency requiring the prompt
      response of experienced clinicians. As it is relatively infrequent, and tends to
      evolve rapidly, decisions concerning care and prognosis must be made promptly.
      Determining etiology is vital since prognosis is largely determined by the cause
      of the illness, and the use of antidotes may be lifesaving. Estimating the
      severity of the liver failure is also important, because if liver transplantation
      is necessary, it must be undertaken quickly. No treatment thus far is better than
      good general care of the comatose patient, with attention to the special problems
      associated with acute liver failure: cerebral edema, infection, circulatory
      collapse. A number of issues have been debated recently, including use of
      prostaglandins and N-acetylcysteine for treatment of all forms of acute liver
      failure, and the use of extracorporeal liver assist machines, however, the
      efficacy of non-specific treatments for this complex syndrome has not been
      proven.

PMID- 9027951
TI  - Circulatory, respiratory, cerebral, and renal derangements in acute liver
      failure: pathophysiology and management.
AB  - Many of the hemodynamic abnormalities seen in acute liver failure (ALF) have now
      been characterized. A lowered systemic vascular resistance with a raised cardiac
      output are prominent features, which in part are modulated by nitric oxide (NO).
      At a cellular level, oxygen supply and utilization are impaired by changes in
      vascular tone, plugging of nutritive vessels, and pathological shunting. The use
      of N-acetylcysteine (NAC) and prostacyclin, a vasodilator, have been shown to
      increase oxygen utilization in the microcirculation. NAC may act by enhancing the
      effect of NO on guanylate cyclase, increasing the formation of cyclic 3',5'
      guanosine monophosphate (cGMP), and thereby resulting in vasodilatation. This
      suggests that despite overproduction of NO in ALF, there is a short-age/ failure
      of utilization at a cellular level. Appropriate management of these patients
      should be based on a good knowledge of the underlying pathophysiology, and thus
      on monitoring, during the course of the disease.

PMID- 9027952
TI  - Bacterial and fungal infection in acute liver failure.
AB  - Patients with acute liver failure (ALF) have increased susceptibility to
      infections, principally as a result of impaired phagocytic function, reduced
      complement levels, and the need for invasive procedures. Bacteriologically proven
      infection is recorded in up to 80% of these patients and fungal infection
      (predominantly candidiasis) in 32%. Clinical signs such as high temperature and
      high WBC are absent in 30% of the cases. Pneumonia accounts for 50% of infective
      episodes, and bacteremia and urinary tract infection a further 20 to 25% each, at
      a median 5, 3, and 2 days, respectively, after the onset of ALF. Selective
      parenteral and enteral antisepsis regimens (SPEAR) were evaluated in prospective
      controlled studies, but early systemic antibiotics alone are as effective as
      SPEAR. With early antibiotics, the incidence of infective episodes is reduced to
      20% and the overall mortality to 44%, with a reduction in progression to
      encephalopathy and an increased opportunity for transplantation.

PMID- 9027953
TI  - The management of abnormalities of hemostasis in acute liver failure.
AB  - The liver is the primary site of synthesis of most coagulation and fibrinolytic
      proteins, and also plays a role in the clearance of hemostasis factors and their
      degradation products. In acute liver failure, these functions are severely
      disturbed, and the risk of hemorrhage is increased. Following a brief summary of
      the physiology of hemostasis, this review describes the nature and frequency of
      hemostatic abnormalities in acute liver failure. These abnormalities include
      quantitative and qualitative platelet defects, impaired synthesis and clearance
      of the coagulation factors and related inhibitory proteins, and enhanced
      fibrinolysis. Disseminated intravascular coagulation may also play a role,
      although this syndrome is difficult to distinguish from changes due to the
      failure of hepatic synthesis and clearance alone. At present, management options
      are limited to support with blood products, although pharmacological manipulation
      of the coagulation and fibrinolytic systems represent a potential area for future
      study.

PMID- 9027954
TI  - Liver transplantation in Europe for patients with acute liver failure.
AB  - Approximately 11% of all liver transplants performed in Europe are for acute
      liver failure, with one-year patient survival rates ranging between 50% and 75%.
      This review summarizes the selection, perioperative management, and outcome of
      patients transplanted for acute liver failure, with particular reference to the
      experience at the Hopital Paul Brousse in Paris and at King's College Hospital,
      London. In both centers, the decision to proceed to liver transplantation is
      based on criteria that predict a survival of less than 20% with medical
      management alone. Infectious complications and cerebral edema remain the most
      common causes of death, and highlight the importance of intensive monitoring and
      early treatment of perioperative complications. In selected patients, auxiliary
      partial orthotopic liver transplantation may be a therapeutic option, with the
      potential for native liver generation and eventual immunosuppression withdrawal
      in approximately two-thirds of patients.

PMID- 9027955
TI  - The American experience with transplantation for acute liver failure.
AB  - Liver transplantation has become the major therapy for acute liver failure (ALF)
      in the United States. Survival rates range from 46% to 89%. Appropriate patient
      selection, timely referral, and management of common complications have improved
      survival. Donor organ shortage may prompt further use of extracorporeal support
      systems and auxillary transplantation in the future. This article reviews the
      American experience of liver transplantation in patients with ALF.

PMID- 9027956
TI  - Use of bioartificial and artificial liver support devices.
AB  - With all the new work and current interest in extracorporeal liver support
      systems incorporating hepatocytes, the findings with earlier artificial systems
      need to be reconsidered, particularly as they may constitute a component of some
      bioartificial devices. Furthermore, new and more effective artificial systems are
      currently under development. Essential hepatic functions need to be replaced,
      including excretory (the capability of adsorbents and dialysis) and synthetic and
      biotransformatory function, but the relative importance of these three functions
      in terms of promoting recovery of the native liver is as yet unclear. Two
      bioartificial devices have already been used clinically in the treatment of acute
      liver failure (ALF): the bioartificial liver (BAL) based on pig hepatocytes
      attached to microcarriers, and the extracorporeal liver assist device (ELAD)
      which contains a human liver-derived tumor cell line. As with earlier completely
      artificial systems, the results so far obtained in man are less impressive than
      in animal models of ALF. An important question not yet answered relates to
      quantity of cells and specific function in the new hybrid bioreactor devices
      required for clinical benefit, as well as the duration of support needed. A
      better understanding of the effects of these devices on the metabolic function of
      the damaged liver and the recovery process will be essential in the further
      development and design of effective systems. Controlled clinical trials on a
      multicenter basis will be needed for proper evaluation of these new approaches to
      treatment of ALF. From our own initial experience, the design of these protocols
      and the selection of biochemical tests will be difficult.

PMID- 9027957
TI  - A 69-year-old man with cholestatic liver disease.

PMID- 9027958
TI  - The Ly-1.1 and Ly-1.2 epitopes of murine CD5 map to the membrane distal scavenger
      receptor cysteine-rich domain.
AB  - CD5 is a member of a superfamily of proteins which contain one or more
      extracellular domains homologous to the type I macrophage Scavenger Receptor
      cysteine-rich (SRCR) domain. The extracellular region of CD5 is composed of three
      SRCR domains (D1, D2, D3). Murine CD5 (mCD5) is polymorphic (Ly-1.1 and Ly-1.2
      alleles), however, the only murine CD5 gene characterized to date encodes the Ly
      1.2 allele (mCD5.2). Likewise, the domain specificity of many of the available
      anti-mCD5 mAb recognizing either Ly-1.1 or Ly-1.2 or both has not been examined.
      Herein we describe the isolation and characterization of cDNA encoding the Ly1.1
      allele (mCD5.1) and map the location and molecular nature of the mCD5 allelic
      variation. We also determined which SRCR domain of mCD5 is recognized by a panel
      of anti-mCD5 mAb. The mCD5.1 protein differs from mCD5.2 in only three amino
      acids, all of which map to the most amino terminal SRCR domain (D1) of mCD5. An
      additional seven silent substitutions were observed in the nucleotide sequence
      encoding mCD5 D1, D2 and transmembrane domains. Immunoglobulin (Ig) fusion
      proteins consisting of various combinations of mCD5.1 or mCD5.2 SRCR domains were
      produced and used to determine that allele specific mAb bound to D1, confirming
      sequence data. MAb against monomorphic determinants on mCD5 bound to each
      mCD5D11g.

PMID- 9027959
TI  - Role of the human CD38 molecule in B cell activation and proliferation.
AB  - Human CD38 is a surface molecule which has been attributed the function of a
      signaling channel leading to cellular activation and proliferation, an ectoenzyme
      with multiple function as well as an inducer of Ca2+ mobilization from
      cytoplasmic stores. The effect mediated by CD38 have been studied in different
      cell populations: the results obtained in human B cells are apparently
      contradictory, with CD38 simultaneously leading to apoptosis in early B cells
      while increasing survival in cells derived from lymph node germinal center. Other
      effects recently reported concern a different potential in terms of signaling in
      early B cells and derived cell lines or in more detailed disease models of human
      leukemia, namely B chronic lymphocytic leukemia cells. To complete the picture of
      the effects mediated by CD38 in the B cell compartment, we have studied the
      signals elicited by ligation of the human molecule in mature B cells from
      circulating pool and also from spleen of normal individuals. The information
      obtained completes the picture of CD38 and mature B cells, where we also studied
      the contribution of relevant cytokines involved in maintenance and
      differentiation of these normal cells, namely IL-1 alpha, IL-2, IL-4 and IL-6.
      Our results indicate that human CD38 plays a key role as a co-receptor in mature
      B cells from normal individuals.

PMID- 9027961
TI  - HLA-B27 presents a peptide from a polymorphic region of its own molecule with
      homology to proteins from arthritogenic bacteria.
AB  - A possible mechanism for the pathogenesis of HLA-B27-associated
      spondyloarthropathies is that peptides from arthritogenic bacteria with homology
      to endogenous self-peptides presented by HLA-B27, including those derived from
      HLA-B27 itself, could elicit an autoimmune T-cell response upon infection. We
      report here that an undecamer corresponding to the polymorphic region of HLA-B27
      spanning residues 169-179 is presented in vivo by the B*2701, B*2704 and B*2706
      subtypes, but was not detected in the B*2703-bound peptide pool. This peptide
      binds to B*2705 in vitro with sufficient affinity to allow its natural
      presentation by this subtype, but it binds with low affinity to B*2703. In spite
      of homology of this peptide to proteins from arthritogenic bacteria, its binding
      specificity does not correlate with current evidence concerning association of
      HLA-B27 subtypes to ankylosing spondylitis, suggesting that presentation of this
      peptide is not the critical feature that determines linkage of HLA-B27 to this
      disease.

PMID- 9027960
TI  - Polymorphisms of TAP1 and TAP2 genes in Graves' disease.
AB  - Graves' disease is an autoimmune disorder in which HLA DQA1*0501 and DQB1*0201
      confer predisposition. The genes for transporters associated with antigen
      processing (TAP1 and TAP2) locate near to HLA DQ coding regions and display only
      a limited degree of polymorphism. Since polymorphisms of TAP might influence
      susceptibility to Graves' disease by a possibly different selection of antigenic
      peptides, we investigated sequence variants of TAP1 and TAP2 genes in 235
      patients with Graves' disease and 218 random healthy controls by polymerase chain
      reaction (PCR) followed by sequence specific oligonucleotide analysis (SSO),
      single strand conformational polymorphism (SSCP) analysis and amplification
      refractory mutation system (ARMS). TAP1*0301 (Val-333/Asp-637: 71% vs. 55% in
      controls, p < 0.008, RR = 2.05) and TAP2*0101 (Val-379/Ala-565/Thr-665/stop-687:
      83% vs. 69% in controls, p < 0.03, RR = 2.20) showed a positive association with
      Graves' disease whereas TAP1*0401 a negative (Ile-333/Gly-637: 4% vs. 13% in
      controls, p < 0.01, RR = 0.25). After selection of patients and controls for HLA
      DQA1*0501 a similar association was found for TAP1*0301 (72% vs. 50% in controls,
      p < 0.02, RR = 2.63) and TAP1*0401 (4% vs. 16% in controls, p < 0.04, RR = 0.22),
      when matching for HLA DQB1*0201 as well as for TAP1*0401 (3% vs. 16% in controls,
      p < 0.05, RR = 0.18). Our findings indicate that the positive association of
      TAP1*0301 and the negative of TAP1*0401 with Graves' disease cannot only be
      explained by linkage disequilibrium between TAP alleles and HLA DQ. Therefore,
      these TAP alleles contribute to genetic susceptibility in Graves' disease as
      additional permissive and protective factors.

PMID- 9027962
TI  - Dermatitis herpetiformis and celiac disease are both primarily associated with
      the HLA-DQ (alpha 1*0501, beta 1*02) or the HLA-DQ (alpha 1*03, beta 1*0302)
      heterodimers.
AB  - HLA-DRB1,-DQA1, and -DQB1 genomic typing of 50 patients with dermatitis
      herpetiformis and of 290 healthy blood donors was performed. Genes encoding the
      DQ (alpha 1*0501, beta 1*02) heterodimer were carried by 43 (86%) of the patients
      and 72 (25%) of the controls. Of the remaining seven patients six (12% of all the
      patients) carried genes encoding the DQ (alpha 1*03, beta 1*0302) heterodimer.
      These HLA associations are very similar to those observed in patients with celiac
      disease. We thus conclude that dermatitis herpetiformis and celiac disease are
      associated to the very same HLA-DQ alpha beta heterodimers.

PMID- 9027963
TI  - An epitope in the third hypervariable region of the DRB1 gene is involved in the
      susceptibility to endemic pemphigus foliaceus (fogo selvagem) in three different
      Brazilian populations.
AB  - Endemic pemphigus foliaceus or fogo selvagem (FS) in an organ-specific autoimmune
      skin disease characterized by epidermal vesicles and mediated by autoantibodies.
      Family cases are frequent and not everyone living in endemic region develops FS
      suggesting that host factors play a role in determining whether exposed
      individuals will be affected. Because our previous works with Brazilian Mestizos
      and with Xavante Indians have shown that particular HLA alleles confer increased
      risk for the disease, we decided to extend these studies to another homogeneous
      population, the Terena Indians. 19 out of 20 Terena patients were either positive
      for DRB1*0404, 1402 or 1406 (p < 0.005, RR = 14). These findings were in
      agreement with the data obtained from the Xavante study. In Mestizos the
      association was with DRB1*01. All these alleles involved in predisposition to the
      disease in different populations shared the same amino acid sequence at position
      67-74 on the third hypervariable region of the DRB1 gene: LLEQRRAA, suggesting
      that inheritance of this sequence is involved in the susceptibility to FS. When
      patients and controls data from different studies were pooled and analyzed
      disregarding the ethnic background and the HLA alleles involved, the results
      obtained clearly supported the hypothesis that matching for this epitope is
      highly significant and predictive of FS predisposition (p < 0.00001, RR = 6.4).

PMID- 9027964
TI  - Diversity and evolution of the DRB1*03 family: description of
      DRB1*03022,*0307,*0308.
AB  - Three previously unreported DRB1*03 alleles are described, adding to the
      diversity of the DRB1 family of alleles. DRB1*03022 contains a silent
      substitution at codon 77. DRB1*0307 differs from DRB1*03011 by a substitution at
      codon 26 resulting in a predicted change from tyrosine to phenylalanine.
      DRB1*0308 is almost identical to DRB1*03011 differing at codon 58 which specifies
      the glutamic acid residue commonly found in DRB1*11 alleles. The new alleles
      (DRB1*03022,*0307,*0308) may have arisen by gene conversion-like events and add
      to the increasing complexity of the HLA system.

PMID- 9027965
TI  - Haplotypic diversity of DQA1*03 and *05 subtypes differing at amino acid residue
      160 encoded in the third exon in 2215 Japanese individuals.
AB  - We analyzed the frequencies and haplotypes of DQA1*03 and *05 subtypes,
      DQA1*03011 or DQA1*0302 and DQA1*0501 or DQA1*0503, respectively, differing only
      at codon 160 in the non-polymorphic third exon of the DQA1 gene. Of these, 1,862
      and 337 individuals selected as DQA1*03- and DQA1*05-positive samples,
      respectively among 2,215 unrelated Japanese were typed for their nucleotide
      variation at residue 160 using PCR-SSP. As observed in other populations, all the
      samples carrying DQA1*03011 (Gene Frequency, GF: 7.8%) were found to share
      DQB1*0302, whereas those carrying DQA1*0302 (GF: 44.3%) were associated with a
      variety of DQB1 alleles including DQB1*0302. Both of the DQA1-DQB1 haplotypes
      with DQA1*03011 and DQA1*0302 carrying DRB1*0406, DQA1*03011-DQB1*0302 and
      DQA1*0302-DQB1*0302, showed a strong linkage disequilibrium with B62 (p < 0.001,
      p < 0.05). These results suggested that DQA1*03011 was generated from a single
      amino acid change at residue 160 in the DQA1*0302-DQB1*0302 haplotype. However,
      none of the haplotypes with two different DQA1*03 subtypes carrying
      DRB1*0403,*0405,*0802 and *0901 showed a linkage disequilibrium with any common B
      locus antigens, revealing extensive haplotypic diversity of the DQA1*03 group.
      For example, DRB1*0802 haplotypes showed linkage disequilibria with two different
      B-locus antigens, B35 and B61 depending on the presence of DQA1*03011 and
      DQA1*0302, respectively. The GFs of DQA1*0501 and *0503 were 5.1% and 2.7%,
      respectively. The DQA1*05 associated haplotypes in the DR52-antigen group with
      DQB1*0301 were divided into two groups, depending on the bimorphism at residue
      160. Such a high degree of haplotypic diversity in association with DRB1 and B
      alleles observed in the DQA1*03 and *05 groups related to amino acid variation at
      residue 160, which may affect biological function such as the interaction between
      CD4 and HLA-DQ molecules, seems to reflect selective pressure in the evolutionary
      process of HLA antigens.

PMID- 9027966
TI  - An unusual DRB1*1503 haplotype without a detectable DRB5 locus in a black African
      family.
AB  - A DRB1*1503 allele not associated with DRB5 locus has been detected in an African
      family during routine HLA typing for bone marrow transplantation. PCR/SSOP
      analysis showed the DR2-associated alleles in all the family members but the DRB5
      locus appeared to be absent in the patient and his brother. The samples were then
      analyzed for the presence of DRB6 pseudogenes and we found that the unusual
      haplotype was associated with DRB6*0101 allele. This finding strengthen the
      hypothesis of a recombination hot spot between DRB1 and DRB6 genes.

PMID- 9027967
TI  - HLA class II genes in Latvian patients with juvenile rheumatoid arthritis.
AB  - PCR-based HLA genotyping was used to analyze the association of HLA-DR and -DQ
      genes in 127 juvenile rheumatoid arthritis patients and 111 population-based
      controls from Latvia. The results show DQA1*03 to be positively associated in
      overall patients and DRB1*01-DQA1*0101-DQB1*0501 to be negatively associated with
      JRA in overall patients and in polyarthritis patients compared to controls. These
      data indicate the immunogenetic heterogeneity in the JRA patients, in the disease
      subgroups and in different ethnic groups. Rheumatoid factor (RF) was assayed in
      patients (n = 119) and controls (n = 98). RF was present in patients (7/119, 6%)
      compared to controls (5/98, 5%). None of the DQA1, DQB1 alleles, DQ and DR-DQ
      haplotypes was associated in seropositive patients compared to seropositive
      controls. DR1-DQ5 (DQA1*0101-B*0501) was decreased in seronegative patients
      (11/111, 10%) compared to seronegative controls (24/105, 23%), but the difference
      was not significant after correction of the p value.

PMID- 9027968
TI  - Development of PCR-SSOP for HLA-A typing of bone marrow registry donors.
AB  - A medium resolution PCR-SSOP typing method, using 26 digoxigenin labelled probes,
      has been established for the identification of HLA-A alleles. The system is
      capable of discriminating all of the serologically defined specificities except
      for eight heterozygous combinations which are however rare in Caucasians. The
      method has been applied to 1,838 individuals on the local bone marrow registry
      who either had only one detectable HLA-A antigen, or a HLA-A antigen whose
      presence had been queried using the serological technique or a broad HLA-A
      specificity assigned by the serological technique. In all but one case the
      serologically assigned antigens were detected with the PCR-SSOP method. In
      addition, PCR-SSOP detected the presence of a second HLA-A allele in over 10% of
      individuals who had been previously homozygous. Frequency information, based on a
      population of 5,000 individuals, has been established using a combination of
      molecular and serological typing data.

PMID- 9027969
TI  - Possible protective role of HLA-B*2706 for ankylosing spondylitis.
AB  - HLA-B27 is strongly associated with ankylosing spondylitis (AS) but the role of
      the HLA molecule itself is still unclear. In this study on Singapore Chinese, we
      have subtyped 50 B27 positive AS patients and 45 B27 positive normals and found
      that the B*2706 allele has a significant negative association with disease (p =
      0.047). Together with recent data indicating the existence of AS "protective" B27
      alleles, our data shows that the HLA molecule itself plays a crucial role in
      disease development.

PMID- 9027970
TI  - Intrathymic maturation of CD4+ T-lymphocytes in an MHC class II deficient
      transplant model.
AB  - Major histocompatibility complex (MHC) class II knockout (class II-) mice fail to
      generate CD4+ CD8- T-lymphocytes. We were interested in determining whether these
      class II- mice could be reconstituted with CD4+ CD8- T-lymphocytes following
      marrow transplantation from normal (class II+) donors. Transplantation of class
      II+ marrow into lethally irradiated class II- recipients failed to generate
      peripheral CD4+ CD8- T-lymphocytes. Unexpectedly, however, transplantation of
      class II marrow into class II+ recipients also resulted in a deficiency of CD4+
      CD8- cells. Analysis of intrathymic T cells showed normal distribution of CD4 and
      CD8 single and double positive or negative thymocytes in normal recipients, while
      class II- recipients always lacked CD4+ CD8- T cells intrathymically. These
      results suggest, therefore, that T-cell maturation in mice requires the presence
      of MHC class II antigens not only in the thymus but also on immature, marrow
      derived pre-thymocytes.

PMID- 9027971
TI  - Polymorphism at the TNF loci in rheumatoid arthritis.
AB  - The purpose of this work was to analyze the possible influence of TNF loci
      polymorphism on the susceptibility and/or the disease profile of rheumatoid
      arthritis (RA). Tumor necrosis factor (alpha and beta) genotypes were determined
      in 60 patients with RA and 102 healthy subjects by a method based on PCR-RFLP
      with amplification-created restriction sites. The results obtained in the present
      study showed that there is not a significant association of either TNF alpha
      promoter variation (at positions -308 and -238) or TNF beta polymorphism with
      susceptibility to RA. However, a significant difference in the mean age at
      disease onset was found between -238 TNF alpha genotypes. In addition, a
      difference in the presence of nodular disease was observed between -308 TNF alpha
      genotype. The results of this study suggests that the TNF alpha gene may play a
      role in the disease profile of rheumatoid arthritis.

PMID- 9027972
TI  - B*78022, a new Caucasian member within the B78 family.

PMID- 9027973
TI  - A new DRB1 allele (DRB1*1125) sharing DR11 and DR8 sequence motifs.

PMID- 9027974
TI  - Identification of a new HLA-DRB1*13 allele (DRB1*1326) with a short DRB1*16
      sequence.

PMID- 9027975
TI  - HLA class II antigens DR4 and DQ8 are associated with allergy to hevein, a major
      allergen of Hevea latex.
AB  - In this study we investigated the relationship between HLA class II alleles and
      the IgE-specific immune response to the 4.7 kDa polypeptide hevein of Hevea
      brasiliensis, a major latex allergen, 51 individuals with immediate-type latex
      allergy and 90 controls were examined for the polymorphisms in exon 2 of HLA
      DRB1, 3, 4, 5 and DQB1 by sequence-specific oligonucleotide probe typing. 35
      (69%) out of 51 latex-sensitized subjects showed positive hevein-specific IgE
      values. Analysis of the HLA data among these 35 subjects revealed increased
      phenotype frequencies for DR4 (22/35, 63%) and DQ8 (18/35, 51%) when compared
      with those in the 16 hevein-negative but latex-positive subjects (DR4: 2/16, 13%,
      p = 0.0009, Pc = 0.047; DQ8: 0/16, p = 0.0003, pc = 0.018) and with healthy
      controls (DR4: 22/90, 24%, p = 0.00012, pc = 0.013; DQ8: 16/89, 18%, p = 0.0003,
      pc = 0.036). Finally the DR4-DQ8 haplotype frequency was significantly elevated
      in hevein-positives when compared with hevein-negatives (51% vs. 0, p = 0.0003,
      pc = 0.034) or controls (51% vs. 18%, p = 0.0002, pc = 0.045) The present data
      suggest DR4 and DQ8 to be operating jointly as susceptibility factor for the
      allergy to hevein.

PMID- 9027976
TI  - Nomenclature for factors of the HLA system, update October 1996.

PMID- 9027977
TI  - Mechanism of action of beta-bungarotoxin, a presynaptically acting phospholipase
      A2 neurotoxin: its effect on protein phosphorylation in rat brain synaptosomes.
AB  - The snake venom phospholipase A2 neurotoxin, beta-bungarotoxin, acts
      presynaptically to alter acetylcholine release in both the peripheral and central
      nervous systems. In investigating the mechanism of this action, we found that
      beta-bungarotoxin inhibited phosphorylation of synapsin I, GAP-43 and MARCKS in
      rat brain synaptosomes. This inhibition was not due to the inhibition of ATP
      synthesis, action of arachidonic acid metabolites, or stimulation of phosphatase
      activities. Furthermore, the activities of Ca2+/calmodulin-kinase II, cAMP-kinase
      and protein kinase C were not altered by beta-bungarotoxin in either synaptic
      plasma membranes or cytosol. When synaptic plasma membranes were treated with
      beta-bungarotoxin, MARCKS phosphorylation was inhibited, and this inhibition was
      overcome by the addition of exogenous protein kinase C. These results suggest
      that the interaction between MARCKS and endogenous protein kinase C is altered by
      beta-bungarotoxin. In contrast, Naja naja atra phospholipase A2, a typical
      phospholipase A2 enzyme, had effects on phosphorylation which were different from
      those of beta-bungarotoxin: (1) inhibition of phosphorylation of synapsin I in
      intact synaptosomes was less potent than that by beta-bungarotoxin; (2) it
      stimulated basal phosphorylation of GAP-43 and MARCKS; and (3) it increased the
      activity of protein kinase C. The inhibition of synapsin I phosphorylation by N.
      n. atra phospholipase A2 in intact synaptosomes may be due to the inhibition of
      ATP synthesis. The stimulation of GAP-43 and MARCKS by N. n. atra phospholipase
      A2 can be explained by the production of arachidonic acid, which stimulated
      protein kinase C activity to a similar extent as that caused by N. n. atra
      phospholipase A2. Thus, the mechanism of action of beta-bungarotoxin appears to
      be quite different from that of a phospholipase A2 enzyme, suggesting that
      phospholipase A2 activity of beta-bungarotoxin may not be essential for its
      action. beta-Bungarotoxin may be a useful tool to study the physiological role of
      phosphorylation of synaptosomal proteins in neurotransmitter release.

PMID- 9027978
TI  - Accelerated evolution of snake venom phospholipase A2 isozymes for acquisition of
      diverse physiological functions.
AB  - The nucleotide sequences of two cDNAs and four genes encoding Trimeresurus
      gramineus venom gland phospholipase A2 (PLA2) isozymes were determined and
      compared internally and externally with those encoding Trimeresurus flavoviridis
      venom gland PLA2 isozymes. It was revealed that the protein-coding regions are
      much more diversified than the 5' and 3' untranslated regions (UTRs) and the
      introns except for the signal peptide domain. The numbers of nucleotide
      substitutions per site (KN) for the UTRs and the introns were approximately one
      quarter of the numbers of nucleotide substitutions per synonymous site (KS) for
      the protein-coding regions and were at the same level as the KN value of T.
      gramineus and T. flavoviridis TATA box-binding protein (TBP) genes, indicating
      that the protein-coding regions of PLA2 isozyme genes are unusually variable and
      that the UTRs including the introns of venom gland PLA2 isozyme genes have
      evolved at similar rate to those of non-venomous genes. The numbers of nucleotide
      substitutions per non-synonymous site (KA) values were close to or larger than
      the KS values for the protein-coding regions in venom gland PLA2 isozyme genes,
      indicating that the protein-coding regions of snake venom gland PLA2 isozyme
      genes have evolved via accelerated evolution. Furthermore, the evolutionary trees
      derived from the combined sequences of the 5' and 3' UTRs and the signal peptide
      domain of cDNAs were in accord with the consequences from taxonomy. In contrast,
      the evolutionary trees from the mature protein-coding region sequences of cDNAs
      and from the amino acid sequences showed random patterns. Estimations of
      nucleotide divergence of genes and the phylogenetic analysis reveal that snake
      venom group IJ PLA2 isozyme genes have been evolving under adaptive pressure to
      acquire new physiological activities.

PMID- 9027979
TI  - Sequence analysis of Lys49 phospholipase A2 myotoxins: a highly conserved class
      of proteins.
AB  - A cDNA clone coding for a putative Lys49 phospholipase A2 myotoxin (ACL myotoxin)
      from Agkistrodon contortrix laticinctus was isolated from a venom gland library
      and sequenced. The sequence of the first 40 amino acid residues of the predicted
      protein matches exactly with the N-terminal sequence of the purified myotoxin.
      Sequence comparison of the predicted sequence of ACL myotoxin and other Lys49 and
      Asp49 phospholipase A2 enzymes shows that the Lys49 phospholipase toxins form a
      highly conserved protein family. In addition to the change at position 49, Lys49
      myotoxins have several invariant residues not found in the Asp49 group, like
      Lys7, Glu12, Thr13, Lys16, Lys78, Lys80, Lys115, and Lys116. There are also some
      conserved residues in the Asp49 group that are not conserved in the Lys49 group:
      Tyr28, Gly32, Gly33. Gly53. Lys49 myotoxins also have a Lys-rich region in the C
      terminus, which is not present in the Asp49 group. These differences clearly
      indicate that Lys49 myotoxins comprise a conserved and distinct class of
      phospholipase A2 enzymes.

PMID- 9027980
TI  - Binding of native kappa-neurotoxins and site-directed mutants to nicotinic
      acetylcholine receptors.
AB  - The kappa-neurotoxins are useful ligands for the pharmacological characterization
      of nicotinic acetylcholine receptors because they are potent antagonists at only
      a subgroup of these receptors containing either alpha 3- or alpha 4-subunits
      (IC50 < or = 100 nM). Four of these highly homologous, 66 amino acid peptides
      have been purified from the venom of Bungarus multicinctus (kappa-bungarotoxin
      (kappa-Bgt), kappa 2-Bgt, kappa 3-Bgt] and Bungarus flaviceps [kappa-Fvt)]. Two
      approaches were taken to examine the binding of these toxins to nicotinic
      receptors. First, venom-derived kappa-Fvt and kappa-Bgt were radioiodinated and
      the specific binding was measured of these toxins to overlapping synthetic
      peptides (16-20 amino acids in length) prepared based on the known sequence of
      the nicotinic receptor alpha 3-subunit. At least two main regions of interaction
      between the toxins and the receptor subunit were identified, both lying in the N
      terminal region of the subunit that is exposed to the extracellular space. The
      second approach examined the importance of several sequence position in kappa-Bgt
      for binding to alpha 3-containing receptors in autonomic ganglia and alpha 1
      containing muscle receptors. This was done using site-directed mutants of kappa
      Bgt produced by an Escherichia coli expression system. Arg-34 and position 36
      were important for binding to both receptor subtypes, while replacing Gln-26 with
      Trp-26 (an invariant in alpha-neurotoxins) increased affinity for the muscle
      receptor by 8-fold. The results confirm that kappa-neurotoxins bind potently to
      the alpha 3-subunit and bind with considerably reduced affinity (Kd approximately
      10 microM) to muscle receptors. Site-directed mutagenesis of recombinant kappa
      Bgt is thus an important approach for the study of structure-function
      relationships between kappa-Bgt and nicotinic receptors.

PMID- 9027981
TI  - Anti-muscarinic toxins from Dendroaspis angusticeps.
AB  - Toxins from the venom of the African green mamba, Dendroaspis angusticeps,
      fulfill a major need for selective ligands for some of the five genetically
      defined subtypes of muscarinic acetylcholine receptors (m1-m5). Two toxins have
      been found that are highly selective antagonists for m1 and m4 receptors (m1
      toxin and m4-toxin, respectively). Two other toxins (MT1 and MT2) bind with high
      affinity to both m1 and m4 receptors, and are agonists. Components of the venom
      also modify the binding of radiolabeled antagonists to m2 receptors, but an m2
      selective toxin has not yet been isolated, m1-Toxin can bind to m1 receptors at
      the same time as typical competitive antagonists, suggesting that this toxin
      binds to the N-terminal and outer loops of m1 receptor molecules, rather than
      within the receptor pocket where typical agonists and antagonists bind. The
      binding of toxins to the outer parts of receptor molecules probably accounts for
      their much higher specificity for individual receptor subtypes than is seen with
      smaller ligands. Toxins are useful for identifying, counting, localizing,
      activating and blocking m1 and m4 receptors with high specificity.

PMID- 9027982
TI  - Snake venom metalloproteinases: structure, function and relationship to the ADAMs
      family of proteins.
AB  - A large number of zinc metalloproteinases of varying mol. wts and biological
      functions has been isolated from crotalid and viperid venoms. Over the past few
      years, structural studies on these proteinases have suggested their organization
      into four classes, P-I to P-IV. These proteinases are synthesized in the venom
      gland as zymogens which are subsequently processed to the active form. The signal
      and pro-sequences of the proteins are highly conserved. Within the pro-domain
      lies a consensus sequence which probably functions in a manner similar to the
      cysteine switch in mammalian collagenases. The proteinase domain is represented
      by two forms: a two-disulfide and a three-disulfide structure. Crystallographic
      and modeling studies suggest that the two forms share very similar tertiary
      structures. The larger venom metalloproteinases (P-II, III and IV) have
      additional domains on the carboxy side of the proteinase domain. The additional
      domains that have been identified include disintegrin and disintegrin-like
      domains, a high-cysteine domain and a lectin-binding domain. It appears that
      these non-enzymatic domains function to modulate the biological properties of the
      proteinases. Recently, a family of homologues of the venom zinc
      metalloproteinases has been described from a variety of organisms including
      mammals, reptiles and invertebrates. This family of proteins has been termed the
      ADAMs, for A Disintegrin-like And Metalloproteinase-containing protein. They
      differ from the venom proteinases in that some of them may not have proteolytic
      activity. In addition to the domain structure described for the P-III class of
      venom proteins, the ADAMs have an epidermal growth factor-like domain, a
      transmembrane domain and a cytoplasmic domain. A description of venom
      metalloproteinase structure will be outlined in this review, along with the
      similarities and differences among the venom proteins and the ADAMs family of
      proteins.

PMID- 9027983
TI  - Characterization of the major metalloprotease isolated from the venom of the
      northern pacific rattlesnake, Crotalus viridis oreganus.
AB  - Rattlesnake venoms typically contain several different metalloproteases, some of
      which are hemorrhagic toxins. Metalloproteases contribute significantly to the
      often severe necrotic changes in tissues following envenomation, and these
      prominent components are important to the predigestive role of venoms. Venom of
      the northern Pacific rattlesnake (Crotalus viridis oreganus) contains at least
      five distinct metalloproteases, and the dominant protease (trivial name, CVO
      protease V) has been isolated and characterized as being a single polypeptide
      chain acidic protein with a molecular mass of 61 kDa and a pH optimum of
      approximately 9.0. It catalyzes the hydrolysis of several protein substrates,
      including casein, and is inhibited by metal chelators such as EDTA, EGTA and 1,10
      phenanthroline but not by serine protease inhibitors such as PMSF. Calcium is
      present at a molar ratio of approximately 1:1, but, unlike other described venom
      metalloproteases, this protease does not appear to contain zinc. Caseinolytic
      activity is not significantly inhibited by citrate (at pH 9.0) at levels up to
      2.0 mM; at 100 mM citrate (at pH 9.0) more than 65% of activity is retained. It
      is partially inhibited by nanomolar concentrations of ATP, but higher amounts
      (micromolar) do not result in further inhibition of activity. The protease shows
      fibrinolytic and fibrinogenolytic activity, but is only weakly hemorrhagic in
      rats. When stored in solution for long periods it undergoes autolytic
      degradation. This protease or a homolog appears to be present in venoms from
      several rattlesnake species but is not present in venoms from juvenile C.v.
      oreganus. The presence of this component in venoms from adult Pacific
      rattlesnakes is responsible for the age-related increase in metalloprotease
      activity of the crude venom.

PMID- 9027984
TI  - Are C-type lectin-related proteins derived by proteolysis of
      metalloproteinase/disintegrin precursor proteins?
AB  - Metalloproteinases and disintegrins, non-enzymatic inhibitors of platelet
      aggregation, are derived by proteolysis from common precursors. A closer
      examination of the cDNA and amino acid sequences of these precursors indicated
      that the putative signal peptide may be an internal hydrophobic segment and that
      the sequences are incomplete at the 5'-region. The studies indicated that C-type
      lectin-related proteins are also derived from the amino terminal region of these
      precursors. Based on these findings, a five-domain structure is proposed for the
      precursors.

PMID- 9027985
TI  - Biochemical characterization of atroxase and nucleotide sequence encoding the
      fibrinolytic enzyme.
AB  - Atroxase, isolated from the venom of Crotalus atrox (western diamondback
      rattlesnake), is a non-hemorrhagic protease which has fibrinolytic activity in
      vitro and in vivo. Fibrin solubilization occurs primarily from the hydrolysis of
      alpha-polymer and unpolymerized alpha- and beta-chains. The enzyme also cleaves
      the A alpha-chain of fibrinogen first, followed by the B beta-chain, and shows no
      effect on the gamma-chain. Although crude venom induces platelet aggregation,
      atroxase demonstrated no ability to induce or inhibit aggregation. Intravenous
      administration of atroxase at a dosage of 6.0 mg/kg resulted in thrombolysis
      within 1 hr followed by recanalization. The primary structure of atroxase was
      deduced from the cDNA encoding the atroxase protein. The venom glands of C. atrox
      were used to prepare a cDNA library. Degenerate oligonucleotides were synthesized
      based on the partial amino acid sequence of atroxase and were used as primers in
      the polymerase chain reaction to amplify overlapping cDNA fragments from the C.
      atrox cDNA library. The resulting cDNA fragments were subcloned, sequenced, and
      translated. The final nucleotide sequence shows high homology to previously
      described primary structures of non-hemorrhagic fibrinolytic proteases isolated
      from snake venom. The base sequence of cDNA obtained from colony hybridization
      also showed comparable results to the cDNA fragment amplified by PCR.

PMID- 9027986
TI  - Similarities and differences in mechanisms of cardiotoxins, melittin and other
      myotoxins.
AB  - Myonecrosis induced in vivo by cardiotoxin, melittin, and Asp49 and Lys49
      phospholipase A2 (PLA2) myotoxins involves rapid lysis of the sarcolemma,
      myofibril clumping, and hypercontraction of sarcomeres. In contrast, skeletal
      muscle necrosis induced by crotamine and myotoxin a is much slower, consisting of
      mitochondrial and sarcoplasmic reticulum swelling, myofibril degeneration, and
      lack of sarcolemma or transverse tubule damage. The mechanisms contributing to
      the myonecrosis induced by these peptides were evaluated. Two cardiotoxins and
      two Lys49 PLA2 myotoxins lysed primary cultures of human skeletal muscle within
      24 hr at a concentration of 0.25 microM, while melittin, crotamine, and myotoxin
      a, and an Asp49 PLA2 myotoxin were non-cytolytic at concentrations up to 5.0
      microM, suggesting that cytolysis is not a good measure of myotoxicity. Crotamine
      and the Lys49 PLA2 myotoxin altered Ca2+ ion flux in human heavy sarcoplasmic
      reticulum by opening the ryanocine receptor. Whole-cell patch-clamp studies
      demonstrated that administrating crotamine intracellularly increased Na+
      currents. Free fatty acids, liberated by activation of tissue phospholipase C or
      by the PLA2 activity of the myotoxins, were monitored for crotamine, myotoxin a
      and a Lys49 PLA2 myotoxin in cell cultures in which the lipids had been
      radiolabeled. Only the Lys49 myotoxin produced significant amounts of fatty acid
      in cell cultures, supporting a potential role for fatty acid production only in
      the mechanism of sarcolemma-destroying myotoxins. These findings, coupled with
      those in the literature, support a hypothesis in which the myotoxins and/or
      products of lipase activity (e.g. fatty acids) are acting at a site existing on
      both the Na+ channel and a protein involved in Ca2+ release and probably serving
      a modulatory function for ion regulation. Based on the similarities in mechanisms
      between the toxins and fatty acids, the most likely site would be a fatty acid
      binding site on the protein (either similar to that on fatty acid binding
      proteins, or an acylated cysteine residue) or in the membrane.

PMID- 9027987
TI  - Erinacin, an antihaemorrhagic factor from the European hedgehog, Erinaceus
      europaeus.
AB  - An antihaemorrhagic factor named erinacin was purified from the skeletal muscle
      extract of the European hedgehog, Erinaceus europaeus, by ammonium sulfate
      precipitation followed by various steps of ion-exchange (DEAE-cellulose),
      absorption chromatography (hydroxylapatite), and gel filtration (cellofine gel).
      A 625-fold purification was achieved with an overall yield of 19%
      antihaemorrhagic activity. The protein effectively inhibited the activity of
      Bothrops jararaca venom haemorrhagin and did not inhibit the enzymatic activity
      of trypsin and chymotrypsin. Erinacin is a large molecule (about 1,000,000 mol.
      wt). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the
      presence of two subunits: one with an apparent mol. wt of 35,000 forming a larger
      subunit (350,000) by cross-linking with disulfide bridges, and a second with a
      mol. wt of 39,000 without disulfides. Dissociation of erinacin into its subunits
      resulted in complete loss of its antihaemorrhagic activity.

PMID- 9027988
TI  - A hypothesis to explain the substrate reactivity of ribosomal and stem-loop RNA
      with ricin A-chain.
AB  - A hypothesis is proposed which explains the low catalytic efficiency of ricin A
      chain on artifical stem-loop RNA substrates, relative to the high catalytic
      efficiency found on intact mammalian ribosomes. The enzymatic binding energy
      required to reach the transition state is greater than that to stabilize the stem
      structure of stem-loop RNA molecules. When artifical stem-loop complexes bind,
      the base-pairing of the stem is lost rapidly relative to catalysis. Loss of
      secondary structure causes movement of the susceptible adenine to a catalytically
      unfavorable geometry and most of the enzyme-substrate complexes dissociate
      without catalysis. The protein architecture of intact ribosomes, when bound to
      ricin A-chain, is proposed to stabilize the stem-loop structure to maintain
      adenine 4324 in a configuration external to the RNA phosphodiester backbone. The
      slow catalysis observed with small stem-loop structures is a consequence of the
      relative probabilities for stem-melting induced by the enzyme and for reaching
      the transition state. Catalysis with a ten-base stem-loop RNA shows product
      formation at a rate of up to 0.02 hr-1, but fails to achieve a full catalytic
      turnover with long incubations. The substoichiometry of product formation with
      small stem-loops is proposed to be a consequence of the competing rates of
      catalysis and enzyme denaturation under in vitro assay conditions. Rates for
      these processes are estimated from the kinetic parameters for ricin A-chain
      hydrolysis of ribosomes and stem-loop structures.

PMID- 9027989
TI  - Structural analysis of ricin and implications for inhibitor design.
AB  - Ricin is a potent cytotoxin with experimental and clinical uses; it has also been
      used as a poison. There is considerable interest in identifying or designing
      inhibitors of the toxin that could be administered as antidotes. The X-ray
      structure of ricin A-chain is known and a plausible mechanism of action has been
      proposed. This provides a structural and chemical framework around which
      inhibitors could be designed; such a structure-based project is underway.
      Computer programs such as DOCK, GRID, SYBYL, and CHEMX have been used to map the
      ricin A-chain binding site and to search for potential inhibitors. Inhibitor
      candidates can be assayed kinetically in a protein synthesis assay and binding
      can be observed crystallographically. Taken together, a workable search algorithm
      has been developed and initial tests indicate that at least one ricin A-chain
      inhibitor, pteroic acid, has been identified.

PMID- 9027990
TI  - An overview of Clostridium perfringens enterotoxin.
AB  - Clostridium perfringens enterotoxin (CPE) is considered to be the virulence
      factor responsible for causing the symptoms of C. perfringens type A food
      poisoning and may also be involved in other human and veterinary illnesses. CPE
      has a unique four-step membrane action that apparently involves: (1) CPE binding
      to a 50,000 mol. wt mammalian protein receptor, forming a small complex of 90,000
      mol. wt; (2) the development of a post-binding physical change to this small
      complex; this physical change could represent either the insertion of CPE into
      the membrane or a conformational change to small complex; (3) an interaction
      between this physically changed small complex and a 70,000 mol. wt mammalian
      protein, forming a large, 160,000 mol. wt complex in membranes; and (4) a
      breakdown in normal plasma membrane permeability properties for small (< 200,000
      mol. wt) molecules. Structure-function analyses have identified a receptor
      binding region at the C-terminus of CPE and indicate that residues in the N
      terminal half of CPE are required for the second step in CPE action to occur.
      Finally, cpe genetic studies are in their infancy but already indicate that cpe
      can be either chromosomal or plasmid-borne and that only a tiny minority of the
      global C. perfringens population is cpe positive. CPE expression appears to be
      transcriptionally regulated during sporulation, at least in part, by regulatory
      factors that are common to all C. perfringens isolates.

PMID- 9027991
TI  - Mass spectrometric investigations on Conus peptides.
AB  - Molecular masses and primary structure determination of Conus peptides, such as
      alpha-, mu- and omega-conotoxins, conantokins and conopressins, were accurately
      measured by state-of-the-art mass spectrometric techniques using only 1-2 pmole
      quantities. Soft ionization of Conus peptides under electrospray, matrix-assisted
      laser desorption and continuous flow frit-FAB conditions produced their
      corresponding singly and multiply charged molecular ions which can be detected by
      mass spectrometric analysis. The molecular masses of Conus peptides were obtained
      by the deconvolution of the multiply charged pseudo-molecular ions. Mixture
      analysis without chromatographic separation can be accomplished by this approach.
      The ions formed during collision-induced dissociation of either singly or
      multiply charged ions of any reduced and derivatized peptide provided the
      corresponding sequences of the amino acids. Preliminary investigations indicate
      that the developed techniques and procedures could be applied in order to
      characterize the peptides present in unknown Conus venoms from the Bay of Bengal
      region.

PMID- 9027992
TI  - A simple biochemical method in the search for bioactive polypeptides in a sea
      anemone (Anemonia sulcata).
AB  - The sea anemone Anemonia sulcata is a well-known natural source of supply of
      biologically active polypeptides. So far, five toxins, ATX I, II, III, IV and AS
      V, several polyvalent protease inhibitors, an elastase inhibitor, two blood
      pressure-depressive polypeptides and very recently peptides that inhibit
      competitively the binding of 125I-dendrotoxin to rat brain membranes and block
      the voltage-sensitive K+ channels, have been isolated from it. The sea anemone
      toxins (especially toxin II of A. sulcata, ATX II) are very important tools in
      neurophysiological and pharmacological research, and their structure-function
      relationship has been investigated. Because of the great scientific value of the
      sea anemone toxins a simplification of their purification procedure was
      elaborated.

PMID- 9027993
TI  - Purification, characterization and immobilization of proteinase inhibitors from
      Stichodactyla helianthus.
AB  - Isolation of proteinase inhibitors from the sea anemone Stichodactyla helianthus
      was achieved by trichloroacetic acid treatment of the aqueous extract followed by
      affinity chromatography on trypsin-Sepharose and ion-exchange chromatography on
      CM-cellulose. The average molecular mass of the major inhibitor (ShPI-I) obtained
      by fast atom bombardment mass spectrometry (FAB-MS) was 6110.6 Da. The amino acid
      sequence was determined by FAB-MS combined with manual Edman degradation,
      digestions with endopeptidases and exopeptidases and automatic sequencing. The
      sequence of ShPI-I (55 amino acids) was compared with those reported in the
      SwissProt database for several proteinase inhibitors and significant similarity
      to inhibitors belonging to the Kunitz family was observed. ShPI-I exhibits a
      broad specificity for serine, cysteine and aspartic proteinases. The dissociation
      constants of the complexes formed with different enzymes were determined. The
      affinity-purified fraction (PI) was immobilized on Sepharose and used in the
      purification of different classes of proteinases.

PMID- 9027994
TI  - Coelenterate venom research 1991-1995: clinical, chemical and immunological
      aspects.
AB  - Important clinical, chemical, and immunological advances in coelenterate venom
      research have been made in recent years. Perhaps the most dramatic advance has
      been in the communication of research data and clinical cases between
      investigators in this field. Results have been processed by the International
      Consortium for Jellyfish Stings through their newsletter and the forthcoming
      publication of the Marine Stinger Book by the University of New South Wales
      Press.

PMID- 9027995
TI  - Development of a protein phosphatase-based assay for the detection of phosphatase
      inhibitors in crude whole cell and animal extracts.
AB  - Diarrhetic shellfish poisoning (DSP) is a serious and globally widespread
      phytoplankton-related seafood illness. Although DSP is rarely life-threatening,
      it causes incapacitating diarrhea and vomiting with no known medical treatments.
      In addition, phytoplankton producing DSP toxins have been identified in temperate
      coastal waters worldwide, and their numbers may be increasing as a result of
      coastal eutrophication. The toxic effects of the major DSP toxins, okadaic acid
      and dinophysistoxin-1 (35-methylokadaic acid), appear to originate from their
      inhibitory activity against a family of structurally related serine/threonine
      protein phosphatases (PSPases). In particular, the inhibition of essential
      PSPases (e.g. PP1 and PP2A) has catastrophic consequences in most eukaryonic
      cells. Exploiting the potent inhibitory property of the DSP toxins, we have
      developed an enzyme-based assay (PP2A assay) capable of detecting both okadaic
      acid and dinophysistoxin-1 in nanogram amounts. The assay employs purified PP2A,
      which has an extremely high affinity for both DSP toxins. This provides the PP2A
      assay with a level of sensitivity comparable to, or surpassing, that of most
      monoclonal antibody probes. To evaluate the PP2A assay as a means of detecting
      contaminated shellfish, a series of spike recovery experiments was conducted. The
      findings from these studies suggest that the PP2A assay has the potential for
      development into a rapid and relatively simple method for detecting PSPase
      inhibitors in crude extracts produced from shellfish.

PMID- 9027996
TI  - Antibodies to maitotoxin elicited by immunization with toxin-fragment conjugates.
AB  - Maitotoxin is a water-soluble polyether toxin produced by the benthic
      dinoflagellate, Gambierdiscus toxicus. Toxin fragments generated by periodate
      oxidation were conjugated to keyhole limpet hemocyanin, and the resulting
      immunogens were used to elicit maitotoxin-specific antibodies in mice. A
      competitive immunoassay developed with polyclonal IgG antibodies detected
      approximately 3 nM purified maitotoxin standard (IC50 approximately 13 nM; 45
      ng/ml) but did not detect other polyether marine toxins. These are the first
      reported maitotoxin-specific antibodies.

PMID- 9027997
TI  - Action of New World scorpion venom and its neurotoxins in secretion.
AB  - New World scorpion venom contains protein toxins specific for ion channels in the
      plasmalemma of excitable cells. The effects were examined of whole venoms from
      Tityus serrulatus, T. bahiensis and T. stigmurus, and some purified toxins in
      isolated nerve endings (synaptosomes) and pancreatic acinar cells. Both systems
      initiated exocytosis in a dose-dependent response to the venom or its bioactive
      protein toxins. Actions differed, however, such that pancreatic acinar cells
      required Ca2+ while cerebrocortical synaptosomes responded by a Ca(2+)-dependent
      mechanism, except in the case of one toxin, IV-5, that elicited a Ca(2+)
      independent response. Membrane depolarization caused by scorpion venom toxins was
      measured via radioisotopic discharge of tetra[3H]phenylphosphonium bromide. The
      role of protein kinase C in second-messenger coupling in pancreatic acinar cells
      is favored over ion-exclusive routes characteristic of synaptosomes.

PMID- 9027998
TI  - Synthesis and expression of the gene coding for noxiustoxin, a K+ channel
      blocking peptide from the venom of the scorpion Centruroides noxius.
AB  - A set of six synthetic overlapping oligonucleotides coding for noxiustoxin were
      coupled into a continuous DNA fragment by means of recursive polymerase chain
      reaction. The polymerase chain reaction product was digested with SalI and
      HindIII, ligated into the E, coli vector pCSP 105 and expressed as a fusion
      protein. The fusion protein was purified and digested with trypsin and the
      hydrolysis products were separated by high-performance liquid chromatography.
      Approximately 1.3 mg of recombinant noxiustoxin per liter of culture was
      obtained. Amino acid analysis and N-terminal amino acid sequence of the
      recombinant noxiustoxin confirmed the nucleotide sequence of the cloned DNA.
      Binding experiments using rat brain synaptosomal membranes revealed that
      recombinant noxiustoxin displaced bound radioactive native NTX with a similar
      efficiency to cold native noxiustoxin.

PMID- 9027999
TI  - Toxins produced by arthropod parasites: salivary gland proteins of human body
      lice and venom proteins of chelonine wasps.
AB  - A review is presented of our ongoing research projects on the protein components
      of the saliva of human body lice and of the non-paralyzing venom of wasps in the
      subfamily Cheloninae. Sodium dodecyl sulfate-polyacryamide gel electrophoretic
      analysis of lice salivary gland proteins showed a predominance of high and
      intermediate mol. wt proteins. Immunoblotting with a low titer polyclonal
      antiserum to lice salivary proteins indicated that some, but not all, of the
      predominant high mol. wt salivary gland proteins are injected into the host
      during feeding. The venom of a Chelonus sp. wasp contains a chitinase, and a
      33,000 mol. wt protein with a primary structure composed mostly of a series of 12
      tandem repeats of a 14-residue sequence. The N-terminus of this protein and its
      homologs in a related species of Ascogaster share a conserved adjacent pair of
      acidic residues. Epitope mapping/immunoprecipitation experiments now in progress
      will provide information on which linear motifs are on the surface of the
      protein, and will thereby provide information on the tertiary structure of the
      protein.

PMID- 9028000
TI  - Characteristics of a developmental arrestant in the venom of the ectoparasitoid
      wasp Euplectrus comstockii.
AB  - Parasitic Hymenoptera regulate their hosts in order to provide a suitable source
      of nutrition and dwelling for their offspring. Few regulatory factors known to
      cause a specific effect on the host have been structurally characterized. The
      larval ectoparasitoid Euplectrus comstockii Howard (Hymenoptera: Eulophidae)
      arrests larval-larval ecdysis in its lepidopteran hosts. Prior to oviposition,
      the female wasp inject a venom into the hemocoel of the host and that venom alone
      is effective in causing the arrestment. A venom gland-reservoir structure
      connected to the lower reproductive tract of the wasp contains a complex mixture
      of proteins. There are no obvious similarities among the electrophoretic banding
      pattern (native or denatured) for venom proteins of E comstockii and several
      other parasitic hymenopteran species. Venomous protein, separated by
      electrophoretic techniques, with a native mol. wt of c. 66,000, was capable of
      arresting larval-larval ecdysis in 4th instar larvae of Trichoplusia ni
      (Lepidoptera: Noctuidae). Nanogram quantities of the protein were sufficient to
      cause arrestment. The activity of the protein was sensitive to temperature, pH,
      organic solvent, and protease.

PMID- 9028001
TI  - Selective alteration of sodium channel gating by Australian funnel-web spider
      toxins.
AB  - The actions of potent mammalian neurotoxins isolated from the venom of two
      Australian funnel-web spiders were investigated using both electrophysiological
      and neurochemical techniques. Whole-cell patch clamp recording of sodium currents
      in rat dorsal root ganglion neurons revealed that versutoxin (VTX), isolated from
      the venom of Hadronyche versuta, produced a concentration-dependent slowing or
      removal of tetrodotoxin-sensitive (TTX-S) sodium current inactivation and a
      reduction in peak TTX-S sodium current. In contrast, VTX had no effect on
      tetrodotoxin-resistant (TTX-R) sodium currents or potassium currents. VTX also
      shifted the voltage dependence of sodium channel activation in the
      hyperpolarizing direction and increased the rate of recovery from inactivation.
      Ion flux studies performed in rat brain synaptosomes also revealed that
      robustoxin (RTX), from the venom of Atrax robustus, and VTX both produced a
      partial activation of 22Na+ flux and an inhibition of batrachotoxin-activated
      22Na+ flux. This inhibition of flux through batrachotoxin-activated channels was
      not due to an interaction with neurotoxin receptor site 1 since [3H]saxitoxin
      binding was unaffected. In addition, the partial activation of 22Na+ flux was not
      enhanced in the presence of alpha-scorpion toxin and further experiments suggest
      that VTX also enhances [3H]batrachotoxin binding. These selective actions of
      funnel-web spider toxins on sodium channel function are comparable to those of
      alpha-scorpion and sea anemone toxins which bind to neurotoxin receptor site 3 on
      the channel to slow channel inactivation profoundly. Also, these modifications of
      sodium channel gating and kinetics are consistent with actions of the spider
      toxins to produce repetitive firing of action potentials.

PMID- 9028003
TI  - Bibliography of toxinology.

PMID- 9028002
TI  - Immunochemical studies of stinging insect venom allergens.
AB  - Several major venom allergens from different insects of the Hymenoptera order
      have been cloned and sequenced by different laboratories. These insects include
      fire ants, honey bees, hornets, yellowjackets and wasps. These venom allergens
      have different biochemical functions, but have one feature in common, their
      varying extents of sequence identity with other proteins in our environment. Our
      studies in mice suggest that recombinant fragments containing regions of sequence
      identity of venom allergen(s) and host protein(s) show antigenic cross
      reactivity. These studies lead to the hypothesis that cross-reactivity of venom
      allergens with host proteins promotes the immunogenicity of venom allergens in
      susceptible people.

PMID- 9028004
TI  - Systemic inflammatory response syndrome in envenoming.

PMID- 9028005
TI  - Light-microscopic studies of 3T3 cell plasma membrane alterations mediated by
      melittin.
AB  - Various light microscopic techniques were used to study the effect of melittin, a
      major toxic constituent of honey bee venom, on plasma membranes of 3T3 mouse
      fibroblasts. Bright-field light microscopy and Trypan Blue dye exclusion were
      used to demonstrate changes in membrane permeability after exposure to melittin.
      Differential interference contrast (DIC) microscopy showed that membrane
      vesiculation induced by melittin was dose dependent. Using both fluorescent lipid
      and glycoprotein markers, we found that membrane vesicles were primarily composed
      of lipids. A sequence of events associated with vesicle formation was depicted by
      DIC and fluorescence microscopy. Confocal laser scanning fluorescence microscopy
      demonstrated a translocation of membrane glycoproteins from the plasma membrane
      to the cytosol following melittin treatment. The significance of membrane
      vesiculation and translocation of membrane glycoproteins in damaged cells is
      discussed.

PMID- 9028006
TI  - Cloning and characterization of cDNAs encoding three isoforms of phospholipase A2
      in Malayan spitting cobra (Naja naja sputatrix) venom.
AB  - cDNAs encoding three phospholipase A2 (PLA2) isoforms in Naja naja sputatrix were
      cloned and characterized. One of them encoded an acidic PLA2 (APLA) while the
      others encoded neutral PLA2 (NPLA-1 and NPLA-2). The specific characteristics of
      APLA and NPLA were attributed to mutations at nt139 and nt328 from G to C and G
      to A, respectively, resulting in amino acid substitutions from Asp20 and 83 in
      APLA to His20 and Asn83 in NPLA. Amino acid sequencing of purified protein also
      showed the presence of this Asp20 and His20 in APLA and NPLA, respectively. The
      cDNA encoding one of the PLA2 (NAJPLA-2A), when expressed in Escherichia coli,
      yielded a protein that exhibited PLA2 activity.

PMID- 9028007
TI  - Blockade of neuromuscular transmission by huwentoxin-I, purified from the venom
      of the Chinese bird spider Selenocosmia huwena.
AB  - Huwentoxin-I (HWTX-I) is a neurotoxic peptide purified from the venom of the
      Chinese bird spider Selenocosmia huwena. The effects of HWTX-I on neuromuscular
      transmission of vertebrate skeletal muscle have been investigated by means of
      twitch tension and electrophysiological techniques. On isolated mouse phrenic
      nerve-hemidiaphragm preparations, HWTX-I blocked the twitch responses to
      indirect, but not to direct, muscle stimulation. The time needed for complete
      block of the neuromuscular transmission was dose dependent. The transmission
      could be mostly restored by prolonged repeated washing with Tyrode's solution. If
      the preparation was pretreated with D-tubocurarine and then immersed in a mixed
      solution of D-tubocurarine and HWTX-I, the washout time necessary to restore the
      neuromuscular transmission was significantly decreased. Intracellular recording
      at the end-plate region of frog sartorius muscle revealed that HWTX-I could
      synchronously reduce the amplitude of the acetylcholine potential induced by
      ionophoretic application of acetylcholine as well as the amplitude of the end
      plate potential evoked by nerve stimulation. Both of these effects eventually
      disappeared; however, both could be restored by prolonged washing. Experiments on
      Xenopus embryonic myocytes indicated that HWTX-I reduced the open probability of
      acetylcholine-induced channel activity, and finally blocked the channel. All of
      these results demonstrated that HWTX-I was a peptide neurotoxin and the
      postsynaptic nicotinic acetylcholine receptor was its site of action.

PMID- 9028008
TI  - Cardiotoxicity of verrucotoxin, a protein isolated from the venom of Synanceia
      verrucosa.
AB  - Freshly purified but unstable verrucotoxin (VTX) and a more stable proteic
      complex of the toxin (p-VTX) were isolated from the venom of the stonefish
      Synanceia verrucosa and applied to frog atrial fibres. VTX and p-VTX decreased
      the amplitude and the duration of the stimulated peak tension and accelerated the
      relaxation phase of the contraction. The negative inotropic effect of p-VTX
      decreased with increasing the external Ca concentration ([Ca]o) in the Ringer
      solution. The negative chronotropic effect induced by p-VTX was insensitive to
      change in [Ca]o. It is reversed by glibenclamide. p-VTX shortened the duration of
      the plateau and the repolarizing phase of the action potential. Glibenclamide but
      not tetraethylammonium reversed the p-VTX-induced shortening of the AP
      repolarizing phase. The data suggest that the toxin isolated from the venom of S.
      verrucosa inhibits Ca channels and might activate ATP-sensitive potassium
      channels in frog atrial heart muscle.

PMID- 9028009
TI  - Occurrence of toxins, other than paralysing type, in the skin of
      Tetraodontiformes fish.
AB  - Puffer fish (Tetraodontidae and Diodontidae) possess paralysing toxins
      (tetrodotoxin and analogues) that are secreted upon stimulation. In a previous
      work it was demonstrated that mucous secretion from the puffer fish Sphoeroides
      spengleri, when mixed in sea water passing through the orobranchial cavity of
      groupers, induced cardiorespiratory alterations. In the present study, skin
      secretions from Ciclichthys spinosus, S. spengleri and Diodon hystrix were tested
      on crustacean nerves, sea urchin eggs and mouse erythrocyte suspensions to verify
      neurotoxic and cytotoxic activities. Ciclichthys spinosus and D. hystrix
      secretions induced transient depolarizations with 0.16 mg and blocked crustacean
      nerve conduction after prolonged exposure. Both secretions had cytotoxic effects;
      when applied to sea urchin eggs they caused cleavage inhibition and anomalies in
      a dose-dependent manner (ED50 +/- S. E. M. = 2.59 +/- 0.08 mg/ml for C. spinosus
      and 1.23 +/- 0.07 mg/ml for D. hystrix); moreover, hemolysis occurred with an
      ED50 = 0.76 mg/ml of 0.5% mouse erythrocyte suspensions to C. spinosus and 0.59
      mg/ml to D. hystrix. These secretions were not lethal in acute toxicity tests,
      even at 335 mg/ml. The neurotoxic components were thermolabile while the
      hemolytic activity was resistant to boiling. Tests with the secretion from S.
      spengleri did not show cytotoxic effects but promptly blocked action potentials
      of crustacean nerves and were lethal for mice in acute toxicity rests. When
      applied to groupers, the C. spinosus secretion caused cardiorespiratory
      alterations. These results suggest the presence of neurotoxins (other than
      tetrodotoxin) and cytotoxins in skin of diodontid puffer fish.

PMID- 9028010
TI  - Melittin and phospholipase A2 from bee (Apis mellifera) venom cause necrosis of
      murine skeletal muscle in vivo.
AB  - Melittin and phospholipase A2 (PLA2) from bee (Apis mellifera) venom were rested
      for their ability to induce necrosis of skeletal muscle cells after intramuscular
      injection into mice. Light and electron microscopic examination of tissue
      indicated that both melittin (4 micrograms/g) and bee venom PLA2 (4 micrograms/g)
      caused necrosis of skeletal muscle cells within 30 min after i.m. injection.
      Early changes in the cells consisted of delta lesions, indicating a ruptured
      plasma membrane, and hypercontraction of myofibrils. By 24 hr the affected cells
      appeared as an amorphous mass of disorganized and disrupted myofibrils contained
      in an intact basal lamina. To ensure that the myotoxic activity of the melittin
      preparation was not due to contaminating. PLA2 activity, the preparation was
      treated with p-bromophenacyl bromide (p-BPB), a known inhibitor of PLA2 activity.
      The p-BPB-treated melittin was determined to have no detectable PLA2 activity
      using a sensitive muscle cell culture assay, and it still induced myonecrosis,
      although to a lesser extent and of a slower onset. Additionally, p-BPB treatment
      of purified bee venom PLA2 completely inhibited its myotoxic activity. These
      results indicate that both melittin and bee venom PLA2 are capable of inducing
      necrosis of skeletal muscle cells upon i.m. injection, and that the catalytic and
      myotoxic activities of bee venom PLA2 are inihibited by p-BPB. Also, melittin and
      contaminating PLA2 in the melittin fraction may be acting synergistically to
      induce a stronger and more rapid myotoxic effect than occurs with either alone.

PMID- 9028011
TI  - Clinical and laboratory alterations in horses during immunization with snake
      venoms for the production of polyvalent (Crotalinae) antivenom.
AB  - Six horses were immunized with the venoms of Bothrops asper, Crotalus durissus
      durissus and Lachesis muta stenophrys for the production of polyvalent
      (Crotalinae) antivenom. During the immunization, clinical and laboratory
      alterations were evaluated in these animals, and the development of humoral
      immune response was followed. Only moderate local tissue changes (edema,
      abscesses, fistules and fibrosis) were observed in these animals, whereas no
      systemic alterations occurred. Regarding laboratory tests, there was a drop in
      hemoglobin concentration and hematocrit, together with an increment in total
      serum protein. Horses developed a moderate leukocytosis, with increments in
      polymorphonuclear leukocytes and lymphocytes. No significant changes were
      observed in prothrombin time or platelet count. There were no alterations in
      serum lactic dehydrogenase and gamma glutamyl transferase activities, whereas
      minor increments in creatine kinase and alanine aminotransferase activities were
      observed, together with a decrease in aspartate aminotransferase. All these
      changes occurred after the injection of 9 mg venom, when sodium alginate was
      first used as adjuvant. Creatinine levels had a small increment, although no
      changes were observed in urea levels or in the urea/creatinine ratio. An
      important individual variability was observed in the humoral immune response, as
      judged not only by enzyme-linked immunosorbent assay, but also by assessing the
      neutralization of the indirect hemolytic activity of venoms.

PMID- 9028012
TI  - Encapsulation of native crotoxin in liposomes: a safe approach for the production
      of antivenom and vaccination against Crotalus durissus terrificus venom.
AB  - Crotoxin, the neurotoxic component of Crotalus durissus terrificus (Cdt) venom
      that displays phospholipase A2 activity, was successfully encapsulated into
      dehydration-rehydration vesicles (DRV/crotoxin) and reverse-phase evaporation
      vesicles (REV/crotoxin) made from sphingomyelin and cholesterol. The
      encapsulation efficiency of native crotoxin was higher in DRV/crotoxin than in
      REV/crotoxin. DRV/crotoxin was not toxic when i.v. inoculated in mice at a dose
      of crotoxin as high as 91 times its L.D50 or when s.c. inoculated at 42 times its
      LD50. On the other hand, crotoxin released from DRV/crotoxin retained its
      original toxicity. REV/crotoxin was found to be at least 1.9 times more toxic
      than DRV/crotoxin. The fact that DRV/crotoxin retained crotoxin more efficiently
      than REV/crotoxin may account for the difference in acute toxicity between the
      two preparations. DRV/crotoxin, when s.c. inoculated in mice, induced anti
      crotoxin antibodies that protected animals against the lethal effect of Cdt
      venom. Following immunization with three doses of DRV/crotoxin (3 x 20 micrograms
      of crotoxin/mouse) and challenge with 8 x LD50 of Cdt venom, 75% of mice were
      protected. The DRV/crotoxin preparation was compared to crotoxin emulsified in
      Freund's adjuvant (FCA/crotoxin). DRV/crotoxin was found to be less toxic than
      FCA/crotoxin, and to induce lower levels of anti-crotoxin antibodies but similar
      levels of protection when inoculated at high doses (20 or 70 micrograms
      crotoxin/mouse). When DRV/crotoxin was adsorbed to alum at the time of
      immunization, it induced antibody and protection levels comparable to those
      produced by FCA/crotoxin.

PMID- 9028013
TI  - Identification of phospholipase A2 and neurotoxic activities in the venom of the
      New Guinean small-eyed snake (Micropechis ikaheka).
AB  - The Papua New Guinean small-eyed snake (Micropechis ikaheka) is recognised as a
      cause of life-threatening envenoming in certain parts of New Guinea. The clinical
      features suggest the presence of toxins acting at the neuromuscular junction and
      on muscle. We have used the mouse phrenic nerve hemidiaphragm preparation, a
      phospholipase A2 assay, and 125I-neurotoxin-binding radioimmunoassays to look for
      toxic activities in the crude venom and in preliminary high-performance liquid
      chromatography (HPLC) fractions. Micropechis ikaheka venom at 1 and 3
      micrograms/ml completely abolished nerve-evoked muscle twitch within 70 min at 37
      degrees C. There was also a sustained contracture of the muscle and some
      reduction in twitch tension evoked by direct stimulation; these were explained by
      the presence of phospholipase A2 activity. The venom inhibited the binding of
      125I-alpha-bungaro-toxin to detergent-extracted human muscle acetylcholine
      receptor (AChR), and inhibited acetylcholine receptor function in a muscle cell
      line. It also inhibited binding of 125I-omega-conotoxin GVIA to detergent
      extracted human frontal cortex voltage-gated calcium channels, but this appeared
      to be dependent on the phospholipase A2 activity. Identification of the main
      neurotoxic fractions following HPLC are shown.

PMID- 9028014
TI  - Isolation, characterization and crystallization of a phospholipase A2 myotoxin
      from the venom of the prairie rattlesnake (Crotalus viridis viridis).
AB  - A myotoxin with phospholipase A2 (PLA2) activity was isolated from the venom of
      the prairie rattlesnake (Crotalus viridis viridis, CVV) by cation-exchange
      chromatography. The toxin contains 123 amino acids and has an estimated mol. wt
      of 14,000. It is basic, with a pI above 9. Comparison of the N-terminal 33
      residues of this myotoxin with other PLA2 proteins from snake venoms showed that
      CVV myotoxin has highest homology (91%) to one isoform of the B component of
      crotoxin from Crotalus durissus terrificus venom, and less homology (73-75%) to
      mojave toxin from Crotalus scutulatus scutulatus venom and agkistrotoxin from
      Agkistrodon halys Pallas venom. It has the least homology (40-43%) to PLA2s from
      venom of two other snakes in the Crotalus genus which are neither neurotoxic nor
      myotoxic. CVV myotoxin induces the type of myonecrosis typical of snake venom
      myotoxins with the PLA2 structure, i.e. rapid disruption of the plasma membrane
      as indicated by the presence of delta lesions, hypercontraction and clumping of
      the myofilaments, and necrosis of affected skeletal muscle cells. Inhibition of
      the phospholipase activity of the toxin with p-bromophenacyl bromide inhibits the
      myotoxic activity, indicating that for some myotoxins with the PLA2 structure,
      the catalytic activity is important for myotoxic activity. This is the first
      report of the isolation of a non-neurotoxic, single-chain PLA2 myotoxin from the
      venom of a snake from the Crotalus genus.

PMID- 9028015
TI  - Cerastatin, a new potent inhibitor of platelet aggregation from the venom of the
      Tunisian viper, Cerastes cerastes.
AB  - Cerastatin, a potent platelet aggregation inhibitor, was purified by gel
      filtration on Sephadex G-75, followed by two ion exchange chromatographies on
      Mono-S columns. Cerastatin is a neutral glycoprotein (pI = 6.2) of 32 kDa, made
      up of at least three subunits. It is devoid of phospholipase A2, esterase,
      fibrinogenolytic and amidolytic activities. It inhibits aggregation of washed
      platelets, induced by either collagen, PAF acether or thrombin, with similar IC50
      of 2.3 nM. Cerastatin also inhibits the thrombin-induced clot retraction of
      platelet-rich plasma. It does not inhibit the amidolytic or the procoagulant
      activities of thrombin Cerastatin caused no lytic effect on platelet membranes
      since it did not cause release of lactate dehydrogenase. Pretreatment of
      platelets with cerastatin irreversibly inhibits the aggregation induced by
      thrombin. Also cerastatin completely inhibits the fibrinogen-induced aggregation
      of alpha chymotrypsin-treated platelets. Cerastatin therefore inhibits platelet
      aggregation by interfering with the interaction of fibrinogen with fibrinogen
      receptors.

PMID- 9028016
TI  - Saxitoxin as a toxic principle of a freshwater puffer, Tetraodon fangi, in
      Thailand.
AB  - Saxitoxin was identified in a freshwater puffer, Tetraodon fangi, which caused
      food poisoning in Thailand. Tetrodotoxin, a puffer toxin, was not detected in the
      species by the HPLC-fluorometric analysis, showing that tetrodotoxin is absent or
      under any detectable level. The result of this study shows that saxitoxin can be
      a major toxin in puffer.

PMID- 9028017
TI  - Assessment of an ovine antivenom raised against venom from the desert black cobra
      (Walterinnesia aegyptia).
AB  - The desert black cobra (Walterinnesia aegyptia) is an elapid widely distributed
      throughout the deserts of Saudi Arabia and currently available antivenoms are
      ineffective in the treatment of its envenoming. Walterinnesia aegyptia venom was
      assessed for several of its physicochemical, enzymatic and biological
      characteristics. An antivenom was raised in sheep using a low-dose immunization
      schedule and digested with papain to provide Fab fragments. The antivenom
      neutralized all of the above enzymatic and biological activities and provided
      good protection in mice (ED50 0.25 g/kg), whereas the commercial polyspecific
      products showed only partial neutralization and did not protect mice.

PMID- 9028018
TI  - Bibliography of toxinology.

PMID- 9028020
TI  - The information processing organisms.
AB  - In spite of the tremendous progress in recent decades of biological science, many
      aspects of the behaviour of organisms in general and of humans in particular
      remain still somewhat obscure. A new approach towards the study of the behaviour
      of man was presented by Heisenberg when he emphasized that a Cartesian view of
      nature as an object "out there" is an illusion in so far as "the observer is
      always part of the formula, the man viewing nature must be figured in, the
      experimenter into his experiment and the artist in the scene he paints."
      (Heisenberg, 1969). The present study is an attempt to make a step forward in
      this direction by focusing on the ways and means of involvement of the observer
      which make him an indelible part of the observation. To get a fresh start let us
      have a look at the physical universe. Although showing an immense variety, all
      objects, living and non-living, have some characteristics in common. They all
      obey the physical laws and they all are engaged in perpetual interactions. How do
      we tell then the difference between living and non-living objects? According to
      the traditional concept it is the capacity for reproduction that distinguishes
      living from non-living objects. (Luria et al., 1981). The non-traditional concept
      presented in this study stresses the way in which objects interact as the crucial
      point of difference between living and non-living objects. This concept claims
      that living objects assert themselves as such only when and while interacting in
      terms of information processing. Under such conditions only, living objects are
      able to display relative independence of the physical laws, for instance active
      movement. This display of relative independence is governed by biological laws
      and defines the behaviour of the living objects as active in principle. All
      objects who share these characteristics are called living, they behave as wholes
      assessing themselves as individuals. The definition suggests that they all share
      the same internal organization which is principally dynamic.

PMID- 9028021
TI  - On fuzzy concepts in immunology.

PMID- 9028019
TI  - The role of constrained self-organization in genome structural evolution.
AB  - A hypothesis of genome structural evolution is explored. Rapid and cohesive
      alterations in genome organization are viewed as resulting from the dynamic and
      constrained interactions of chromosomal subsystem components. A combination of
      macromolecular boundary conditions and DNA element involvement in far-from
      equilibrium reactions is proposed to increase the complexity of genomic
      subsystems via the channelling of genome turnover; interactions between
      subsystems create higher-order subsystems expanding the phase space for further
      genetic evolution. The operation of generic constraints on structuration in
      genome evolution is suggested by i) universal, homoplasic features of chromosome
      organization and ii) the metastable nature of genome structures where lower-level
      flux is constrained by higher-order structures. Phenomena such as 'genomic
      shock', bursts of transposable element activity, concerted evolution, etc., are
      hypothesized to result from constrained systemic responses to
      endogenous/exogenous, micro/macro perturbations. The constraints operating on
      genome turnover are expected to increase with chromosomal structural complexity,
      the number of interacting subsystems, and the degree to which interactions
      between genomic components are tightly ordered.

PMID- 9028022
TI  - Effect of relevance shifts in category acquisition: a test of neural networks.
AB  - The effect of changing the validity of stimulus dimensions in the course of
      category learning was investigated. Contrary to previous experiments on
      interdimensional relevance shifts, a family resemblance stimulus structure was
      used that allowed for the direct comparison of performance on items learned
      before and after the relevance shift. In both experiments, the test performance
      was dominated by information that was acquired after the relevance shift. The
      results indicate that the acquired knowledge of the 2 learning phases was not
      integrated, but knowledge learned before the shift was partly replaced by
      information acquired after the shift. Simulation of the results by the
      independent cue model, the configural cue model, and ALCOVE (attention learning
      covering map) demonstrates that these models must be expanded by a mechanism that
      inhibits the integration of information acquired before and after the relevance
      shift.

PMID- 9028023
TI  - Event-related potentials differentiate the effects of aging on word and nonword
      repetition in explicit and implicit memory tasks.
AB  - Explicit memory declines with age while implicit memory remains largely intact.
      These experiments extended behavioral findings by recording event-related
      potentials (ERPs) in young and elderly adults during repetition priming and
      recognition memory paradigms. Words and pronounceable nonwords repeated after 1
      of 3 delays. Stimuli were categorized as either word-nonword or old-new. Repeated
      items elicited more positive-going potentials in both tasks. Hemispheric
      asymmetries for word and nonword processing were observed during lexical
      decision: Repetition effects were larger over the left hemisphere for words and
      over the right hemisphere for nonwords. For the young, ERP repetition effects
      were larger during recognition memory. For old adults, conversely, repetition
      produced more positive-going waveforms during lexical decision. The elderly had
      ERP and behavioral deficits at long recognition delays. ERP repetition effects in
      the elderly, like behavioral performance, were preserved in an implicit task but
      impaired in an explicit memory task.

PMID- 9028024
TI  - Bias in auditory priming.
AB  - Priming for previously studied words in an implicit auditory memory task has been
      interpreted as evidence for a presemantic perceptual representation system that
      encodes acoustic representations of words (B. A. Church & D. L. Schacter, 1994).
      In this article, 3 experiments provided evidence that such priming may result
      instead from a bias to respond with studied words. In forced-choice
      identification with similar alternative choices, there was no overall improvement
      in performance due to prior study. Benefits for studied test words were offset by
      costs for similar but nonstudied test words. Prior study had no effect when
      forced-choice alternatives were dissimilar. The data are discussed in relation to
      current models of auditory information processing and a new model (R. Ratcliff &
      G. McKoon, in press) for priming in visual word identification.

PMID- 9028025
TI  - Do vision and haptics share common representations? Implicit and explicit memory
      within and between modalities.
AB  - Previous assessments of verbal cross-modal priming have typically been conducted
      with the visual and auditory modalities. Within-modal priming is always found to
      be substantially larger than cross-modal priming, a finding that could reflect
      modality modularity, or alternatively, differences between the coding of visual
      and auditory verbal information (i.e., geometric vs. phonological). The present
      experiments assessed implicit and explicit memory within and between vision and
      haptics, where verbal information could be coded in geometric terms. Because
      haptic perception of words is sequential or letter-by-letter, experiments were
      also conducted to isolate the effects of simultaneous versus sequential
      processing from the manipulation of modality. Together, the results reveal no
      effects of modality change on implicit or explicit tests. The authors discuss
      representational similarities between vision and haptics as well as image
      mediation as possible explanations for the results.

PMID- 9028026
TI  - Temporal distinctiveness and modality.
AB  - It has been proposed that auditory stimuli are more temporally discriminable in
      memory than visual stimuli. Studies using the continual-distractor paradigm have
      provided both supporting and contradictory evidence for this hypothesis. The
      conflicting reports differed, however, in the modality of the interleaved
      distractor tasks. The present experiments manipulated both word and distractor
      task modality. Results showed that aurally presented word lists were more
      sensitive to temporal schedules of presentation when the distractor task was
      auditory than when it was visual. The same effect was not consistently found for
      visually presented word lists. Such an interaction may help explain the
      previously reported disparate findings and suggests that the auditory modality,
      in the presence of silent distraction, can reduce participants' use of temporal
      distinctiveness information at retrieval.

PMID- 9028027
TI  - Implicit (and explicit) learning: acting adaptively without knowing the
      consequences.
AB  - Subjects exposed to members of a structured domain become sensitive to the
      general structure of that domain, even when unaware that the domain has such
      structure. Numerous investigators have taken this as evidence for a mode of
      learning in which memory passively and unselectively absorbs the structure of the
      environment. The authors contend that this assumption miscasts the fundamental
      nature of learning. The authors demonstrate that even when task and stimulus
      structure are held constant, subjects react to variations in incidental stimulus
      properties by processing the stimuli in qualitatively different ways. The authors
      conclude that implicit learning, just like explicit learning, proceeds through
      active organization of the stimulus complex, rather than through passive
      absorption of any level of structure. The authors propose a synthesis in which
      learning, with and without awareness, is understood through a common set of
      principles.

PMID- 9028028
TI  - Hidden covariation detection: a fundamental and ubiquitous phenomenon.
AB  - H. Hendrickx, J. De Houwer, F. Baeyens, P. Eelen, and E. Van Avermaet (1997)
      reported a series of (mostly unsuccessful) studies on nonconscious hidden
      covariation detection (HCD); for example, they reported that out of 3 attempts to
      replicate P. Lewicki et al.'s studies, only 1 produced the expected results. They
      concluded that HCD may be not as general and robust as the previous research
      suggested, and they considered boundary conditions. In this article, the authors
      discuss a number of weaknesses of H. Hendrickx et al.'s experiments (and
      systematic deviations from the original methodology) that are potentially
      responsible for the lack of the expected results and discuss missing facts in
      their arguments (e.g., they failed to mention any published replications of the
      HCD studies from other than the present authors' laboratories). It is argued that
      when all evidence is considered, the proper conclusion is that nonconscious
      processing of covariations is not only general and robust but also a ubiquitous
      phenomenon mediating a variety of processes of acquisition of information.

PMID- 9028029
TI  - The relationships between psychometric intelligence and learning in an explicit
      and an implicit task.
AB  - An experiment is reported examining the relation of implicit grammar learning and
      series completion tasks to a standard measure of psychometric intelligence, the
      Wechsler Adult Intelligence Scale-Revised (WAIS-R; D. Wechsler, 1981). The
      results replicate and extend an earlier study by A. S. Reber, F. F. Walkenfeld,
      and R. Hernstadt (1991) and provide the following support for the differences
      between explicit and implicit tasks: (a) The implicit task was less strongly
      related to Full Scale IQ, and (b) the implicit task appeared to be independent of
      age. The implicit and explicit tasks exhibited a quite different pattern of
      relations to the factors known to underlie WAIS-R performance. Although both
      tasks showed significant links with a Perceptual Organization factor, only the
      series completion task showed a significant link with the Attention factor.

PMID- 9028030
TI  - List-context effects in evaluative priming.
AB  - Evaluative priming effects are often found in the evaluative decision task, in
      which persons judge the affective connotation (positive vs. negative) of a target
      word. The present experiments examined list-context effects to test whether
      evaluative and semantic priming follow the same laws. In Experiment 1, evaluative
      priming was found at prime-target stimulus onset asynchronies (SOAs) of 0 ms and
      100 ms, but not at SOAs of--100, 200, 600, and 1,200 ms. Experiment 2 manipulated
      SOA (0, 200, and 1,200 ms) and the proportion (25%, 50%, and 75%) of the prime
      target pairs that were evaluatively related. Contrary to the typical finding that
      increases in the proportion of related prime-target pairs lead to increased
      priming at long but not short SOAs, an effect of consistency proportion was found
      at SOAs of 0 ms (for reaction times) and 200 ms (in the accuracy data), but not
      at the 1,200-ms SOA. The pattern of results is discussed in relation to possible
      explanatory mechanisms of evaluative priming.

PMID- 9028031
TI  - Micro-assay method for evaluating the allergenicity of the major soybean
      allergen, Gly m Bd 30K, with mouse antiserum and RBL-2H3 cells.
AB  - A micro-assay method for evaluating the allergenicity of soybean allergen was
      developed by using the mouse antiserum against Gly m Bd 30K, a major soybean
      allergen, and RBL-2H3, a rat mucosal mast cell line. The antiserum against Gly m
      Bd 30K was prepared by subcutaneously immunizing BALB/c mice with the allergen.
      The behavior by affinity-chromatography and the properties against heat treatment
      show that the reaginic activity of the antiserum resided in the IgE antibody
      specific for Gly m Bd 30K. The developed assay method is shown to be useful for
      simulating IgE mediated type-I allergy and to be highly sensitive for detecting
      the allergen.

PMID- 9028032
TI  - Immune bioactivity in shellfish toward serum-free cultured human cell lines.
AB  - The biologically functional effect of eight kinds of hot-water extracts of
      shellfish on cultured human cell lines was examined in a serum-free medium model.
      Meretrix lusoria and Sinonovacula constricta extracts enhanced IgM secretion of
      both hybridoma HB4C5 and SI102 cells when cultured with the respective extracts.
      The purified principle exhibited remarked activity in the adsorbed fraction in
      hydroxyapatite and Concanavalin A columns. The extracts of Corbicula fluminea,
      Crassostreas gigas, Meretrix lusoria, Anadara granosa, and Sinonovacula
      constricta enhanced in nitroblue tetrazolium (NBT)-reducing ability of macrophage
      U-M cells. Meretrix lusoria, Anadara granosa, and Sinonovacula constricta were
      specifically cytotoxic to both cultures of MCF-7 breast cancer cells and HuH-6KK
      hepatoblastoma. These findings imply that the extracts of shellfish that were
      examined exhibited a differential effect on immune cells and tumor cells.

PMID- 9028033
TI  - Protein, and dietary fiber-rich new foodstuff from brewer's spent grain increased
      excretion of feces and jejunum mucosal protein content in rats.
AB  - We made a new protein-rich and fibrous foodstuff by milling and sieving brewer's
      spent grain. This product contained glutamine-rich protein and the dietary fibers
      cellulose, hemicellulose, and lignin. We called this product germinated barley
      foodstuff (GBF). GBF had the effect of increasing fecal dry weight and number of
      feces and of significantly increasing jejunum mucosal protein content in rats
      over the cellulose group. In GBF, Gln-rich protein is thought to have strong
      chemical bonds with dietary fiber, an arrangement which would be important in the
      way these physiological effects arise. As dietary supplements of Gln or dietary
      fibers (i.e., cellulose, hemicellulose, lignin, and a mixture of these) did not
      improve defecation and jejunum mucosal protein simultaneously, the effects of GBF
      are thought to be caused not by the individual ingredients, but by the
      combination of protein with dietary fiber.

PMID- 9028034
TI  - Analysis of low temperature inducible mechanism of gamma-glutamyltranspeptidase
      of Escherichia coli K-12.
AB  - Escherichia coli K-12 cultured at 20 degrees C has more gamma
      glutamyltranspeptidase (GGT: EC 2.3.2.2) activity than that cultured at 37 or 42
      degrees C. On Western blot analysis, E. coli K-12 cells cultured at 20 degrees C
      produced more GGT protein than those cultured at 37 degrees C. mRNA of the GGT
      gene (ggt) in the cells was also measured and it was found that the level of ggt
      mRNA at 20 degrees C was 10-fold higher than that at 37 degrees C. When the ggt
      promoter was replaced by a tac promoter, GGT activity at 37 degrees C from the
      tac promoter was 5-fold higher than that at 37 degrees C from the ggt promoter,
      though there was less difference in GGT activity between both grown at 20 degrees
      C. The ggt mRNA at 20 degrees C was found to be more stable than that at 37
      degrees C. These results suggested that the higher GGT activity in E. coli K-12
      cells grown at 20 degrees C was due to a higher level of GGT protein at 20
      degrees C caused by higher level of ggt mRNA at 20 degrees C because of a low
      temperature dependent ggt promoter as well as the stability of ggt mRNA at 20
      degrees C.

PMID- 9028035
TI  - Purification and characterization of a thermostable pyruvate kinase from the
      actinomycete Microbispora thermodiastatica.
AB  - The pyruvate kinase of Microbispora thermodiastatica was purified to homogeneity
      and some properties of the enzyme were characterized. The molecular weight of the
      enzyme by gel filtration is 277,000. The subunit molecular weight is 55,000 by
      SDS-polyacrylamide gel electrophoresis, and only one N-terminal amino acid
      sequence was obtained. It had a pH optimum around pH 4.5 to 7.0 and was stable
      over the range of pH 4.0-8.0. The enzyme is thermostable and no activity was lost
      after heat treatment at 55 degrees C for 60 min. AMP activated this enzyme and
      the saturation curve of the enzyme for PEP changed from sigmoidal type to
      hyperbolic type in the presence of AMP.

PMID- 9028036
TI  - Molecular cloning of an inulin fructotransferase (depolymerizing) gene from
      Arthrobacter sp. H65-7 and its expression in Escherichia coli.
AB  - The gene encoding an extracellular inulin fructotransferase (depolymerizing)
      (inulase II) (EC 2.4.1.93), designated ift gene, was cloned from the genomic DNA
      of Arthrobacter sp. H65-7, and expressed in Escherichia coli for the first time.
      Sequence analysis showed a single open reading frame consisting of 1314 base
      pairs that encoded a signal peptide of 32 amino acids and a mature protein of 405
      amino acids. The primary structure showed a homology of 49.8% with that of the
      inulin fructotransferase (DFA I-producing) (EC 2.4.1.200) from Arthrobacter
      globiformis S14-3. E. coli cells carrying the ift gene produced the active enzyme
      under control of the lac promoter. The expression of the ift gene was improved by
      a plasmid, pIFT-B, in which the ift gene was immediately downstream from the lac
      promoter. An E. coli transformant carrying pIFT-B expressed twice as much
      activity of inulase II as that of the original strain, Arthrobacter sp. H65-7.
      Most of the enzyme activity existed within the cells.

PMID- 9028037
TI  - Novel extracellular alkaline metalloendopeptidases from Vibrio sp. NUF-BPP1:
      purification and characterization.
AB  - We found two types of novel alkaline metalloendopeptidases (AP1 and AP2) from a
      marine bacterium, isolated from the intestine of a five-barred goatfish
      (Parupeneus trifasciatus) and identified as Vibrio sp. (NUF-BPP1). We studied the
      structure-function relationship of these marine bacterial proteases. The
      electrophoretically homogeneous proteases had a molecular mass of 48 kDa for AP1
      and 36 kDa for AP2 on SDS-PAGE, and showed optimum activity at around pH 9.5-10.0
      (casein as substrate). Calcium chloride (5 mM) stabilized the activities over pH
      6-11, but o-phenanthroline and EDTA inhibited the activities of both AP1 and AP2.
      The EDTA-inactivated proteases were partly restored to activity by addition of
      either zinc or calcium. Sodium chloride (3.5 M) increased the activities toward Z
      Gly-Leu-NH2. N-Terminal sites of hydrophobic amino acid residues (Leu, Ile, Phe,
      Tyr, and Trp) of the peptide substrates were cleaved by AP1 and by AP2. Autolysis
      of AP1 in the absence of calcium ion probably produced AP2 by releasing a
      fragment (molecular mass of about 12 kDa) from the C-terminal end of AP1.

PMID- 9028038
TI  - Hesperidin as an inhibitor of lipases from porcine pancreas and Pseudomonas.
AB  - In the course of our screening work for new types of lipase inhibitors,
      hesperidin was identified as a simple and small molecular weight inhibitor in the
      peels of Citrus unshiu. Hesperidin inhibited lipase activity from porcine
      pancreas and that from Pseudomonas, and their IC50 was 32 and 132 micrograms/ml,
      respectively. Hesperidin, neohesperidin, narirutin, and naringin are known as the
      main flavonoids in Citrus unshiu. Neohesperidin also inhibited the lipase from
      procine pancreas, but did not have any effect on Pseudomonas. Narirutin and
      naringin did not show this effect on lipases from porcine pancreas and
      Pseudomonas. In animal experiments, the concentration of plasma triglyceride in
      rats fed a diet containing 10% hesperidin were significantly lower than that fed
      the control diet.

PMID- 9028039
TI  - Effects of an Escherichia coli ilvA mutant gene encoding feedback-resistant
      threonine deaminase on L-isoleucine production by Brevibacterium flavum.
AB  - A mutated ilvA gene of Escherichia coli encoding a threonine deaminase that is
      resistant to feedback inhibition by L-isoleucine was obtained. It was functional
      in Brevibacterium flavum, and a wild strain of B. flavum into which it was
      introduced became able to convert exogeneous L-homoserine and L-threonine to L
      isoleucine. When it was introduced into a L-threonine-producing B. flavum strain,
      the transformant accumulated 20 g/liter L-isoleucine from 100 g/liter glucose.

PMID- 9028040
TI  - The role of microsomal beta-glucuronidase in ascorbic acid biosynthesis
      stimulated by xenobiotics in rats.
AB  - We (Horio et al., 1993) have reported that the stimulation of the expression of
      the UDPglucuronosyltransferase (UDPGT) gene played a key role in the ascorbic
      acid biosynthesis induced by xenobiotics, such as 3-methylcholanthrene (3MC) and
      phenobarbital (PB). beta-Glucuronidase catalyzes the hydrolysis of glucuronide
      formed by UDPGT. The role of microsomal beta-glucuronidase in ascorbic acid
      biosynthesis induced by xenobiotics was investigated using homozygous and
      heterozygous EHBRs (Eisai hyperbilirubinuria rats) which are deficient in
      microsomal beta-glucuronidase. Homozygous EHBRs, heterozygous EHBRs, and Sprague
      Dawley (SD) rats were injected intraperitoneally once with 3MC (20 mg/kg body
      weight), or once a day for 2 d with PB (100 mg/day kg body weight). In these
      three strains of rats, the hepatic level of xenobiotics-inducible UDPGT mRNA was
      elevated similarly by the treatment with xenobiotics. The increases of the
      hepatic concentration of ascorbic acid and the urinary excretion of ascorbic acid
      by the treatment with 3MC or PB were markedly suppressed in both EHBRs compared
      with those in the control SD rats. These results indicate that the microsomal
      beta-glucuronidase has an important role in the hepatic ascorbic acid
      biosynthesis induced by xenobiotics.

PMID- 9028041
TI  - Purification and characterization of dipeptidyl aminopeptidase from
      Aureobacterium sp. WO26.
AB  - We isolated a bacterial strain with an enzyme which releases dipeptide from Gly
      Arg-p-nitroanilide. The bacterium was tentatively identified as Aureobacterium
      sp. The enzyme, named AuDAP, was purified and characterized. It was homogenous by
      SDS-PAGE and IEF, and had a molecular mass of 90,000 Da by SDS-PAGE and 88,000 Da
      by gel filtration, so it may be a monomer. The isoelectric point was 3.8 and the
      optimum pH was 10.0. The purified enzyme hydrolyzed Gly-Arg-pNA, a model
      substrate for DAP I, and Arg-Arg-MNA, a model substrate for DAP III. However,
      this enzyme did not hydrolyze Gly-Phe pNA, also a model substrate for DAP I.
      These results suggested that this enzyme did not fall under the classification of
      mammalian DAPs and was similar to DAP BI from Pseudomonas sp. WO24 and dDAP from
      Dictyostelium discoideum, although several differences were observed between
      them. The N-terminal amino acid sequence of this enzyme showed no significant
      homology to any enzyme and protein, except only for DAP BI.

PMID- 9028042
TI  - A novel NADP(+)-dependent serine dehydrogenase from Agrobacterium tumefaciens.
AB  - NADP(+)-dependent serine dehydrogenase [EC 1.1.1.-], which catalyzes the
      oxidation of the hydroxyl group of serine to form 2-aminomalonate semialdehyde,
      was purified to homogeneity from a crude extract of Agrobacterium tumefaciens ICR
      1600. The enzyme had a molecular mass of about 100 kDa and consisted of four
      identical subunits. In addition to L-serine, D-serine, L-glycerate, D-glycerate,
      and 2-methyl-DL-serine were substrates. However, O-methyl-DL-serine and L
      threonine were inert. The enzyme showed maximal activity at about pH 9 for the
      oxidation of L-serine. The enzyme required NADP+ as a coenzyme, NAD+ was inert.
      The enzyme was not inhibited by EDTA, o-phenanthroline, or alpha,alpha'
      dipyridyl, but was inhibited by HgCl2, p-chloromercuribenzoate, L-cysteine, D
      cysteine, malonate, 2-methylmalonate, and tartronate. The Michaelis constants for
      L-serine, D-serine, and NADP+ were 42, 44, and 0.029 mM, respectively.

PMID- 9028043
TI  - Bone resorption inhibitors from hop extract.
AB  - We searched hop extract for active component(s) that inhibited bone resorption in
      the pit formation assay, and isolated xanthohumol and humulone as active
      ingredients. Especially humulone had extraordinarily strong inhibitory activity
      and the IC50 (concentration of 50% inhibition) value was 5.9 x 10(-9)M.

PMID- 9028044
TI  - Protection by trehalose of DNA from radiation damage.
AB  - The most serious damage to cells exposed to radiation is attributed mostly to
      effects on the structure of cellular DNA. We found that trehalose protects DNA
      from irradiation. In the presence of 10 mM trehalose, DNA can be protected from
      about 4 times higher doses of beta- and gamma-ray irradiation. The protective
      effect increases with the amount of the sugar. Other disaccharides, sucrose, and
      maltose had similar effects.

PMID- 9028045
TI  - Neoagarobiose as a novel moisturizer with whitening effect.
AB  - Neoagarobiose, a disaccharide, showed a higher hygroscopic ability than glycerol
      or hyaluronic acid, typical moisturizing reagents. Beside, neoagarobiose whitened
      B16 murine melanoma cells, and showed low cytotoxicity. Therefore neoagarobiose
      was a rare reagent showing both moisturizing and whitening effects.

PMID- 9028046
TI  - Isolation and molecular characterization of four arginine/glutamate rich
      polypeptides from the seeds of sponge gourd (Luffa cylindrica).
AB  - Four arginine/glutamate rich polypeptides referred to as 5 k-, 6.5 k-, 12.5 k-,
      and 14 k-AGRPs were purified to homogeneity by gel filtration on Sephadex G-75
      followed by CM-cellulose, butyl-Toyopearl 650 M, and reverse-phase HPLC from the
      seed of sponge gourd (Luffa cylindrica). Tricine SDS-PAGE indicated that 5 k- and
      6.5 k-AGRPs are single polypeptides, but 12.5 k- and 14 k-AGRPs consist of two
      polypeptide chains, which are linked by disulfide bond(s). The N-terminal amino
      acid sequences of four AGRPs were analyzed by a gas-phase sequencer, and the
      result indicated that they are distinct molecules. Comparison of the sequences
      with those of proteins in the protein data base demonstrates that 5 k- and 6.5 k
      AGRPs have a significant homology with a basic peptide from pumpkin seeds and
      with cocoa seed vicilin, respectively, and that 12.5 k- and 14 k-AGRPs are
      related to 2S seed storage proteins. Furthermore, it was assumed that the four
      AGRPs might occur in the protein bodies within cells of the seed.

PMID- 9028047
TI  - Quantitative analysis of alkylpyrazines in regular- and low-fat commercial peanut
      butter preparations.
AB  - A simple, modified version of the selective purge and trap method was applied for
      a quantitative analysis of the trace amount of pyrazines present in both regular-
      and low-fat commercial peanut butter preparations. A total of 33 volatile
      compounds were identified, the three most abundant individual pyrazines being 2,5
      (or 2,6)-dimethylpyrazine, 2-ethyl-6-methylpyrazine, and pyrazine which comprised
      55-79% of the total pyrazine concentration. Minor or trace quantities of
      thiazoles, oxazoles, pyrroles, and pyridine were also identified in the sample.

PMID- 9028048
TI  - Isolation and characterization of chitinase from a flake-chitin degrading marine
      bacterium, Aeromonas hydrophila H-2330.
AB  - A flake-chitin degrading marine bacterium was isolated and identified as
      Aeromonas hydrophila. This strain secreted five chitinases and an beta-N
      acetylglucosaminidase. The main chitinase (Chi-A) was purified and characterized.
      The optimum pH of Chi-A was 5-8, and the activity was inhibited by Hg2+ and Fe3+.
      Chi-A was different from chitinases of other Aeromonas species with respect to
      molecular weight (62,000) and insensitivity to monoiodoacetate. The amino
      terminal amino acid sequence showed extensive similarity with chitinases from
      Gram-negative bacteria.

PMID- 9028049
TI  - Isolation and identification of alpha-glucosidase inhibitors from tochu-cha
      (Eucommia ulmoides).
AB  - alpha-Glucosidase inhibitory activity was found in aqueous methanol extracts of
      tochu-cha, dried leaves of Eucommia ulmoides (Eucommiaceae). Five active
      principles against yeast enzyme were isolated and characterized. Among them,
      quercetin (1, Ki: 8.5 x 10(-6) M) was considered to contribute mostly to the
      activity of the tochu leaves. In regard to an animal alpha-glucosidase, rat
      intestinal sucrase activity was also inhibited by 1.

PMID- 9028050
TI  - Rapid detection method for bacteriocin and distribution of bacteriocin-producing
      strains in Lactobacillus acidophilus group lactic acid bacteria isolated from
      human feces.
AB  - A new screening method, using micro plate wells, was developed for detecting the
      bacteriocin producer in lactic acid bacteria. The method was applied for
      screening the bacteriocin producer in L. acidophilus group lactic acid bacteria
      isolated from human feces with 19 bacteria used as indicator strains. Of the 98
      strains, 62 were finally selected as the bacteriocin producers, including 39
      strains positive against at least one of food-borne pathogenic bacteria.

PMID- 9028051
TI  - Mechanism of stereospecific conversion of DL-5-substituted hydantoins to the
      corresponding L-amino acids by Pseudomonas sp. strain NS671.
AB  - The mechanism of stereospecific conversion of DL-5-substituted hydantoins to the
      corresponding L-amino acids by Pseudomonas sp. strain NS671 was studied. The
      results indicated that the hydantoinase catalyzed the hydrolysis reaction of both
      D- and L-5-(2-methylthioethyl)hydantoin, and that the hydrolysis of the L
      enantiomer proceeded preferentially compared with that of the D-enantiomer. On
      the basis of these findings, the mechanism was speculated to be as follows: DL-5
      substituted hydantoins are converted exclusively to the L-forms of the
      corresponding N-carbamyl-amino acids by the hydantoinase in combination with
      hydantoin racemase. The N-carbamyl-L-amino acids are then converted to L-amino
      acids by N-carbamyl-L-amino acid amidohydrolase.

PMID- 9028052
TI  - Increased stability of PEG-PPG conjugated human urokinase against autolysis.
AB  - Human urokinase (UK) was easily degraded during the incubation at 37 degrees C in
      a time-dependent manner. The degradation was also observed in the presence of
      trypsin inhibitors, suggesting that UK was not degraded by exogeneous trypsin
      like serine protease but by autolysis. In this cases, the A-chain of UK was
      selectively degraded. Polyethylene glycol-polypropylene glycol conjugated
      urokinase (PEG-PPG-UK) was not degraded after prolonged incubation at 37 degrees
      C. These results demonstrated that PEG-PPG modification completely blocked the
      degradation of UK by autolysis.

PMID- 9028053
TI  - Changes of lipoxygenase and fatty acid hydroperoxide lyase activities in bell
      pepper fruits during maturation.
AB  - Developmental changes in fatty acid hydroperoxide lyase (HPO lyase) and
      lipoxygenase (LOX) during the maturation of bell pepper fruits (Capsicum annuum
      L. cv. Kyonami) were examined by means of activity measurements, immunological
      detection of both the enzymes, and analysis of the volatile compounds formed upon
      homogenization of the fruits. Both the enzyme activities decreased with
      maturation, and immunological studies showed that the amounts of the enzymes
      concomitantly decreased. The amounts of six-carbon aldehydes and alcohols formed
      from bell pepper fruits upon homogenization also decreased during maturation, and
      with the fully ripened red fruits, these volatile compounds were hardly
      detectable. These results suggest that the major factor contributing to the
      changes in the composition of volatile compounds during the maturation of bell
      pepper fruits was changes in the amounts of HPO lyase and LOX.

PMID- 9028054
TI  - High efficiency transformation of Bacillus brevis by electroporation.
AB  - Various conditions in the Bacillus brevis transformation by electroporation were
      investigated to increase the efficiency. Competent cell volume and presence of
      polyethylene glycol 6000 and single stranded DNA on pulsing were critical for the
      efficiency. As a result, we established the improved method by which 10(7)-10(8)
      transformants/microgram plasmid DNA could be obtained.

PMID- 9028055
TI  - Inhibitory effect of green tea on injury to a cultured renal epithelial cell
      line, LLC-PK1.
AB  - When cells from a cultured renal epithelial cell line, LLC-PK1, were cultured
      under hypoxic conditions (oxygen concentration of 2% or less) before
      reoxygenation was applied (95% air, 5% CO2), the leakage of lactate dehydrogenase
      (LDH) into the medium increased. This phenomenon was inhibited in the presence of
      dimethyl sulfoxide, a hydroxyl radical scavenger, suggesting the involvement of
      free radicals. Such oxidative stress was significantly inhibited by a green tea
      extract, and more potently by a tannin mixture. On the other hand, under ordinary
      culture conditions (95%, air, 5% CO2), there was cell injury, although the LDH
      leakage was less than that under hypoxia/reoxygenation, and such injury was
      inhibited by the green tea extract and the tannin mixture.

PMID- 9028056
TI  - Increase in lysophosphatidylethanolamine in the cell membrane upon the regulated
      exocytosis of pancreatic acinar AR42J cells.
AB  - A specific cytosolic phospholipase A2 inhibitor, arachidonyl trifluoromethyl
      ketone (AACOCF3), was found to inhibit the regulated exocytosis of pancreatic
      acinar AR42J cells. When AR42J cells were stimulated with cholecystokinin
      octapeptide (CCK-8), the regulated exocytosis monitored by amylase release was
      rapidly activated and increased by 2.5-fold during one hour. After AR42J cells
      were treated with AACOCF3, amylase release by CCK-8 remained at the basal level.
      Thus, changes in the composition of membrane phospholipids before and after
      stimulation were investigated. Within 1 min after CCK-8 stimulation,
      lysophosphatidylethanolamine (lysoPE) in the cellular membranes of AR42J was
      increased while lysophosphatidylcholine stayed unchanged. In the presence of
      AACOCF3, lysoPE was not increased by CCK-8. Those results indicate that the
      increment of lysoPE is linked to the regulated exocytosis.

PMID- 9028058
TI  - Spatial constructions by capuchin monkeys.
AB  - Spontaneous object grouping by two capuchin monkeys (Cebus apella) ranging from 1
      to 4 years of age was investigated. Subjects' spontaneous interactions with
      groups of objects were recorded. Similarly to human infants and chimpanzees,
      capuchins increased with age the size of groups, the rate of vertical
      constructions, and of contemporaneous groups, i.e., of groups made simultaneously
      or close to another. However, capuchins lagged behind human infants and, partly,
      to chimpanzees in that they failed to develop alignments of objects, or spatial
      correspondences between contemporaneous groups. Capuchins' constructive processes
      were similar to those of chimpanzees and different from those of human infants.
      Nonhuman primates increasingly manipulate objects together with the same part of
      their body. In these instances, no specific spatial relations among objects as
      detached units are detectable. In fact, objects are related to one another only
      incidentally to the simultaneous relations of each object to the self. Therefore,
      nonhuman primates increasingly manipulate objects in relation to their body.

PMID- 9028057
TI  - Opioid-immune interactions in autism: behavioural and immunological assessment
      during a double-blind treatment with naltrexone.
AB  - The emerging concept of opioid peptides as a new class of chemical messengers of
      the neuroimmune axis and the presence of a number of immunological abnormalities
      in infantile autism prompted us to correlate biological (hormonal and
      immunological) determinations and behavioural performances during treatment with
      the potent opiate antagonist, naltrexone (NAL). Twelve autistic patients ranging
      from 7 to 15 years, diagnosed according to DSM-III-R, entered a double-blind
      crossover study with NAL at the doses of 0.5, 1.0 and 1.5 mg/kg every 48 hours.
      The behavioural evaluation was conducted using the specific BSE and CARS rating
      scales NAL treatment produced a significant reduction of the autistic
      symptomatology in seven ("responders") out of 12 children. The behavioural
      improvement was accompanied by alterations in the distribution of the major
      lymphocyte subsets, with a significant increase of the T-helper-inducers (CD4+CD8
      ) and a significant reduction of the T-cytotoxic-suppressor (CD4-CD8+) resulting
      in a normalization of the CD4/CD8 ratio. Changes in natural killer cells and
      activity were inversely related to plasma beta-endorphin levels. It is suggested
      that the mechanisms underlying opioid-immune interactions are altered in this
      population of autistic children and that an immunological screening may have
      prognostic value for the pharmacological therapy with opiate antagonists.

PMID- 9028059
TI  - Biological parameters influencing the immunological response to plasma derived
      and recombinant hepatitis B vaccines.
AB  - Personnel (1856 subjects) belonging to local health units (medical and
      paramedical staff) that have been vaccinated since 1984 against hepatitis B virus
      (HBV) with HBsAg plasma purified preparations (Hevac-B and H-B-Vax) or
      recombinant DNA preparation (Engerix-B) were followed in plasma anti-HBs antibody
      levels. At the end of the protocols, different seroconversion percentages and
      different anti-HBs levels were reached: the best results were obtained with
      Engerix-B. Sex and principally age influenced the antibody production: women
      generally reached highest protective antibody levels and the 21-30 year group was
      more responsive than other groups. The injection of a supplementary 4th or 5th
      dose in low or non-responders could restore the specific immunity in the majority
      of the subjects and increase the anti-HBs level. The time course after the
      immunization of antibody levels depended on the level reached at the end of
      vaccination schedule. These data suggest that different antibody level
      monitorings of vaccinated subjects, planned on the basis of the antibody level
      reached at the end of vaccination, could prevent a loss of protection against the
      HBV infection.

PMID- 9028061
TI  - Determination of chromium and nickel in commercial foam bath products by ETA-AAS.
AB  - The presence of some inorganic elements, such as Ni and Cr in cosmetic products
      could be responsible for some skin diseases, such as allergic dermatitis. This
      paper deals with the determination of these two elements in commercial samples of
      foam bath products by means of the ETA-AAS technique. Four different analytical
      procedures for sample digestion are evaluated and discussed. Results indicated
      that the high-pressure microwave digestion is the best procedure for treatment of
      the complex matrices considered in the study. Chromium values were in the range
      of 22-199 micrograms/kg, whereas those of nickel fell within the range 26-287
      micrograms/kg. The detection limit (3 sigma) of the whole procedure was 3
      micrograms/kg for Cr and 15 micrograms/kg for Ni. The analytical data
      demonstrated that both Ni and Cr were present in all the samples at very low
      concentrations, and that foam bath products are a relatively minor source of
      exposure to these elements.

PMID- 9028060
TI  - Micellar electrokinetic capillary chromatographic analysis of platelet activating
      factor in human blood by indirect ultraviolet detection.
AB  - In this paper, 1-O-hexadecyl and 1-O-octadecyl-2-acetyl-sn-glycero-3-
      phosphorylcholine (C16-AGEPC and C18-AGEPC) in the platelet activating factor of
      human blood were analyzed by micellar electrokinetic capillary chromatography
      (MECC) with indirect ultraviolet absorption detection at 254 nm. The optimum
      running buffer for the separation contained 50 mmol/l sodium dodecy sulphate, 20
      mmol/l potassium hydrogen phthalate, 10 mmol/l borax and 3 mol/l urea (pH 6.8).
      The separation was completed within 10 min. The detection limits of C16-AGEPC and
      C18-AGEPC were the same, i.e. 60 ng/ml (k = 3). The analytical precision (n = 6)
      was 2.8-3.0% and 1.4-1.7% for the determination (peak height mode) and for the
      measurement of the migration times, respectively. The application of this method
      to the clinical samples was demonstrated.

PMID- 9028062
TI  - Treating tuberculous pleurisy with effusion by artificial pneumothorax.
AB  - The efficacy of artificial pneumothorax therapy was evaluated in subjects with
      tuberculous pleurisy with effusion. The patients (57 cases) were divided into two
      groups at random: 30 cases in the control group and 27 cases in the group under
      treatment. They were all given standard treatment with antituberculous drugs
      drawing liquid accumulated and injecting antituberculous drugs and
      corticosteroids into their intrapleural cavity. In addition, the treating group
      received artificial pneumothorax to enhance the treatment efficacy. The frequency
      and amount of liquid drawn in the treating group were obviously less than those
      in the control group. Time necessary to draw all the liquid was substantially
      shortened in the former case with a higher degree of efficiency (92.59%) than
      that of the latter (83.33%). We also found that the artificial pneumothorax could
      raise the intrapleural pressure of 2 to 4 cm H2O, reduce leakage in parietal
      pleura and evidently increase the absorption in visceral pleura. The results
      suggest that artificial pneumothorax can reduce the liquid leakage and accelerate
      absorption of the liquid in thorax. As the two layers of pleura can be isolated
      by the air in thorax, the occurrence rate of pleural adhesion can be cut down.
      Hence, it is an effective assistant therapy for tuberculous pleurisy with
      effusion.

PMID- 9028063
TI  - [Surgical treatment of T4 primary lung cancer].
AB  - We investigated 257 T4 primary lung cancer patients who received operation in 30
      hospitals of a lung cancer surgical therapy group of Chubu and present the
      results of questionnaires on the outcomes of surgical treatment for the T4 cases.
      T4 cases were classified as follows; 147 resections (57.4%); 110 exploratory
      thoracotomies (42.8%) ; 90 pleural dissemination and pleural effusions; 33 aorta;
      30 left atrium and 17 superior vena cava. Survival rate of the T4 lung cancer
      patients in resection group and exploratory thoracotomy group were respectively
      49.1% and 37.8% for one-year survival rate, and 15.1% and 4.7% for three-year
      survival rate. P of these two groups was 0.06 from Logrank test. Thirty three
      patients (21 resection and 12 exploratory thoracotomies) survived for two years
      and more. The number of cases by invasive organ was 17 pleural disseminations and
      effusion, 4 aorta, 4 left atrium and 3 mediastinum. We questionnaire on surgical
      operation for T4 cases with poor prognosis and obtained the result that half of
      the hospitals were positively performing surgery and the other half revealed a
      policy avoiding surgery.

PMID- 9028065
TI  - [Treatments for T4 advanced lung cancer with invasion to the superior vena cava].
AB  - We discussed on the treatments for T4 lung cancer with invasion to the superior
      vena cava, whose prognosis has been poor. However, surgical resection may improve
      the prognosis compared with radiation therapy. The prosthetic replacement of
      superior vena cava can be done safely, and its patency is good in cases of ring
      enforced ePTFE graft. Although superior vena caval obstruction syndrome had been
      a hard issue in the advanced cases, stenting in superior vena using the
      interventional radiological technique is a safe and reliable method. We should
      consider the stenting as the first choice for superior vena cava obstruction
      syndrome, because it makes the QOL improve so much.

PMID- 9028064
TI  - [The significance of surgical treatment for T4 lung cancer].
AB  - A total of 114 pT4 patients underwent pulmonary resection from January 1980 to
      December 1993 at our hospital. The overall five-year survival rate of the 114
      cases was 17%. There was no significance between the five-year survival rate of
      squamous cell carcinoma and that of adenocarcinoma. Five-year survival rates of
      17 patients with N0 disease, 29 patients with N1 disease, 51 patients with N2
      disease, 1 patients with N3 disease, and 16 patients with NX disease were 40%,
      21%, 21%, 0%, and 0%, respectively. Five-year survival rate of 89 cases with
      single factor of T4 was 24% and that of 25 cases with more than one factor was 4%
      (0.05 < P < 0.1). In the patients with only single factor of T4, five-year
      survival rates of 6 patients with left atrium invasion, 13 patients with major
      vessel invasion, 9 patients with trachea/carina invasion, and 18 patients with
      vertebral body, were 50%, 38%, 22%, and 0%, respectively. Furthermore, in 38 pT4
      patients with involvement only to single adjacent structure, five-year survival
      rates were 47% in curative operation (n = 17) and 10% in non-curative operation
      (n = 21) (P < 0.05). We conclude that surgical treatment for T4 lung cancer
      should be performed to patients with single structure invasion which is expected
      to have a curative operation. N0 disease is more favorable than N1 or N2 disease.

PMID- 9028066
TI  - [T4 lung cancer: surgical indications based on results of surgical treatment].
AB  - During the period of 1981 and 1995, 54 patients with T4 lung cancer underwent
      pulmonary resection in our institutes. The actuarial survival rate of them was
      30% at three years and 12% at five years. The five-year survival rate of 12
      patients with complete resection was 33%. On the other hand, the five-year
      survival rate of 30 patients with incomplete resection was 9%. The five-year
      survival rates of 17 patients with N0 disease, 9 patients with N1 disease, and 22
      patients with N2 disease were 13%, 40%, and 5%, respectively. There was a
      significant difference in survival between patients with N1 and N2 disease. Four
      patients survived for more than five years after the operation : two patients had
      invasion to the left atrium and two had a slight degree of pleural dissemination.
      Radical pulmonary resection may yield long-term survival in T4 lung cancer
      patients having invasion to the left atrium.

PMID- 9028067
TI  - [A successful removal of T4 lung cancer with its left atrial extension using
      cardiopulmonary bypass].
AB  - A 42-year-old man presented with cough, chest pain and dyspnea. The chest
      roentgenogram revealed a large mass shadow in the right upper and middle lobes
      with atelectasis and pleural effusion. Massive polypoid tumor extending into the
      left atrium was diagnosed by computed tomography and two dimensional
      echocardiography. In order to prevent sudden death and cardiac failure, surgery
      was performed. At first, the polypoid tumor in the left atrium was removed with a
      partial resection of the left atrial wall under cardiac arrest using
      cardiopulmonary bypass. Then, a right pneumonectomy was performed. Episodes of
      embolism were not observed during surgery. His postoperative course was almost
      favorable. The size of the tumor in the right lung was 18 x 15 x 8 cm and the one
      in the left atrium was 6.5 x 4.5 x 3 cm, respectively. Pathological examination
      of the resected specimen revealed the evidences of large cell carcinoma extending
      into the left atrium. Local recurrence with S9 metastasis of the left lung were
      detected 6 months after surgery, and he died 6 months later. It is emphasized
      that the extended surgery using cardiopulmonary bypass was useful for both
      prevention of embolism and improvement of quality of life.

PMID- 9028068
TI  - [Surgical treatment of T4 lung cancer: combined resection of lung and heart or
      great vessels].
AB  - From 1980 to 1995, sixteen patients with T4 lung cancer underwent resection of
      left atrium (LA) or great vessels combined with pulmonary resection. For eight
      patients with lung cancer invading LA, LA was resected under simple clamp of LA
      in seven cases, and under extracorporeal circulation in one case. For three
      patients with lung cancer invading aorta, resection and reconstruction of aorta
      was performed under femoro-femoral bypass in one case, and under temporary bypass
      using a heparin-coated tube in two cases. For five patients with lung cancer
      invading superior vena cava (SVC), SVC was resected under partial clamp or simple
      clamp of SVC in each case. In remaining three patients, SVC was resected under
      internal bypass in one case, and under temporary bypass using a heparin-coated
      tube in two cases. Three were two operative deaths, one (SVC) died of acute heart
      failure, and the other (LA) died of acute respiratory distress syndrome. Four
      patients are alive without recurrence and three of them (one LA and two SVC) have
      been surviving more than five years after operation.

PMID- 9028069
TI  - [Assessment of surgery for primary lung cancer with dissemination or malignant
      effusion of pleura (T4 advanced lung cancer)].
AB  - Twenty-four cases of primary lung cancer with dissemination or malignant effusion
      of pleura detected preoperatively or intraoperatively were surgically treated at
      our hospital. Mean survival time (MST) and two-year survival rate (2 YSR) were
      analyzed on their resected cases and non-resected cases with similar lesion. MST
      and 2 YSR of 19 cases with lobectomy, 5 cases with pneumonectomy including
      pleuropneumonectomy and 15 cases with no surgical procedure were 2.77 +/- 0.60
      years, 53.4%, 1.51 +/- 0.50 years, 26.7% and 0.99 +/- 0.15 years, 6.7%. MST and 2
      YSR of 13 cases with lymph node dissection under R 1 and 6 cases over R 2 on
      lobectomy group were 1.99 +/- 0.38 years, 37.5% and 5.66 +/- 1.71 years, 66.7%.
      These findings suggested that lobectomy with lymph node dissection of R 2 over
      may be a beneficial treatment of lung cancer with dissemination or malignant
      effusion of pleura.

PMID- 9028070
TI  - [Results of surgical treatment of T4 lung cancer].
AB  - A total of 381 patients with primary lung cancer including 30 cases of T4 lesion,
      were surgically treated at our hospital from June 1975 through July 1996.
      Extended resection was performed in 11 patients. The 5-year survival rate after
      operation for all cases of T4 lung cancer, including one with operative death was
      15.2%. Six patients who had curative operation showed no significant prolonged
      survival when compared to 24 patients who resulted in non-curative operation, but
      the median survival time of the former was longer than that of the latter. Six
      patients survived over 3 years; malignant pleurisy and/or intrathoracic
      dissemination of lung cancer were existed in 3 cases of those patients. In
      conclusion, extended resection for patients with T4 lung cancer should be limited
      to patients who are expected to have curative operation.

PMID- 9028071
TI  - [Outcome from surgery of lung cancer invading the carina].
AB  - By 1995, 17 patients with lung cancer invading the carina underwent surgical
      resection and reconstruction of the carina. Procedures which applied to patients
      were two cases of wedge pneumonectomy, seven cases of sleeve pneumonectomy, four
      cases of carinal reconstruction with right upper lobectomy, and four cases of
      carinal resection and reconstruction. Overall survival for five years were 40.3%
      and 33.6% for ten years survival. Operative death occurred in 5 cases. Long term
      survival was achieved in localized diseases which showed no lymph node extension.
      As for N1 and N2 diseases, only one patient among 7 cases survives 12 months.
      Thus we conclude that selected cases which showed localized disease without lymph
      node extension are the candidate for carinal resection and reconstruction.
      Postoperative intensive care is mandated for these patients. Adjuvant therapy
      with surgery for these patients with lymph node progression is a future problem.

PMID- 9028072
TI  - [A case report of type A dissection of the aorta presenting as a superior vena
      cava syndrome 10 years after aortic valve replacement].
AB  - Aortic dissection usually result in chest pain and back pain. This patient is a
      58 year-old man who received aortic valve replacement for aortic regurgitation 10
      years ago. In this case, the patient had superior vena cava syndrome as a result
      of a painless aortic dissection. The superior vena cava was compressed by the
      ascending aorta itself, which had become very large but had not ruptured into the
      mediastinum. He underwent modified Carbrol's operation under hypothermic
      cardiopulmonary bypass and circulation arrest on May 8, 1995. Dissecting aneurysm
      in the late term after aortic valve replacement is rare, and for it to result in
      superior vena cava syndrome is especially rare.

PMID- 9028073
TI  - [A curative report of multiple organ dysfunction syndrome and disseminated
      intravascular coagulation due to methicillin-resistant Staphylococcus aureus
      caused mediastinitis after cardiac surgery].
AB  - We experienced a curative case, who was a fifty nine-year old man suffered from
      multiple organ dysfunction syndrome (MODS) and disseminated intravascular
      coagulation (DIC) due to Methicillin-resistant Staphylococcus aureus (MRSA)
      caused-mediastinitis following cardiac surgery against atrial septal defect (ASD)
      and tricuspid regurgitation. We successfully treated him with mediastinal
      irrigations by a large quantities of physiological saline containing 1% Povidone
      iodine (PI) and MRSA sensitive antibiotics as well as artificial supports such as
      plasma pheresis and hemodialysis against failure organs. It may be due to the
      prompt treatment with mediastinal irrigation and well timed dosage of sensitive
      antibiotics against the origin of sepsis that such a serious patient like this
      case could be recovered from MODS and DIC. In addition, it may be very effective
      to irrigate with 1% PI against MRSA-caused-mediastinitis.

PMID- 9028074
TI  - [A case report of aortic valvuloplasty by rasping technique for aortic stenosis
      with small annulus simultaneously performed with mitral valve replacement].
AB  - The patient was a 48-year-old woman with aortic stenosis and regurgitation and
      mitral stenosis. Preoperative cardiac catheterization revealed LV-Ao pressure
      gradient of 30 mmHg and regurgitation of Sellers III. The aortic annulus was
      measured less than 19 mm. As operative findings, the aortic annulus seemed to be
      too small to be replaced with 19 mm prosthetic valve. Aortic valvuloplasty (AVP)
      with rasping technique was performed for the aortic valve and valve replacement
      was carried out for the mitral valve. After aortic declamping and occurring her
      beat, the transesophageal echocardiographic evaluation for AVP was effective.
      Postoperative course was uneventful. Postoperative cardiac catheterization have
      shown decreased transvalvular pressure gradient up to 10 mmHg and aortic
      regurgitation of Sellers I.

PMID- 9028075
TI  - [A case of localized pleural mesothelioma].
AB  - Localized pleural mesothelioma is reported. A 62-year-old male had been observed
      as a patient with old tuberculosis of the left lung for a few decades. For
      detailed examination of fever of unknown cause and abnormal shadow on the chest X
      ray, the patient was introduced to our hospital. By percutaneous cytodiagnosis,
      the illness was diagnosed as pleural mesothelioma, and the patient underwent
      surgery. Since adhesion of the tumor to the lower lobe of the lung was extremely
      tight, the tumor and the left lower lobe were resected as a mass. The tumor was
      about 15 cm in diameter, weighed 1,300 g and a slight pleural effusion was
      observed. The tumor was diagnosed as malignant localized pleural mesothelioma
      pathologically. Localized pleural mesothelioma should be subjected to surgery in
      the early stage, in principle. Even in cases difficult to diagnose, operation
      should not be delayed by repeating easy-going needle-biopsy or a long-term
      treatment with antitubercular drugs. The postoperative course of this case has
      been good, and no recurrence nor metastasis has been detected.

PMID- 9028076
TI  - [A case report of anterior mediastinal cystic lymphangioma].
AB  - Fourty seven years old woman came to our hospital for further examination of
      incidentally found abnormal chest shadow. Chest US examination revealed lobulated
      cystic mass. The cyst wall was thin and smooth. Chest computed tomography showed
      water density cystic mass. Preoperative diagnosis was pericardial cyst. Operation
      was done. Lobulated cyst was attached to pericardium and diaphragma. Though
      adhesion to the pericardium was loose, adhesion to the diaphragma was tight. To
      achieve complete resection of the cyst, partial resection of the diaphragma was
      needed. Postoperative course was uneventful. Cystic lymphangioma is benign but
      complications such as infection or bleeding were reported. Then complete
      resection of the cyst should be done.

PMID- 9028077
TI  - [A case of systemic arterial supply to the normal left basal segments with no
      symptoms].
AB  - A 41-year-old man was admitted to Hirakata City Hospital because of an abnormal
      shadow on chest X-ray film. Chest X-ray film showed a tumorous shadow in the left
      anterior basal segment (S8). MRI showed aberrant arteries arose from the
      descending aorta clearly. Broncho-fibers-copy showed no defect of visible
      bronchi. Aortography showed one aberrant arteries arose from the descending
      thoracic aorta, circulated in the basal segment of the left lower lobe, and
      returned to the left pulmonary vein. Pulmonary arteriogram revealed defect of A8
      10. Resection of left lower lobe was performed. In the resected specimen, the
      bronchi of the left lower lobe had a normal structure and showed a normal pattern
      of distribution.

PMID- 9028078
TI  - [The differences of the cerebral and spinal vessels in sensitivity to PaCO2 and
      vasoconstrictors].
AB  - We investigated the differences in the response to arterial CO2 tension and
      vasoconstrictors between the cerebral and spinal vasculatures using cranial and
      spinal window technique which provided the direct observation of pial vessels.
      Pentobarbital anesthetized dogs (n = 18) (CO2 tension; n = 6 and vasoconstrictor;
      n = 12) were instrumented for measurement of pial vessel diameters by intravital
      microscopy in the cranial and spinal window preparation simultaneously. We
      achieved hypocarbia (20-25 mmHg) followed by adjusting CO2 levels for normocarbia
      (35-40 mmHg) and for hypercarbia (55-60 mmHg) using CO2 gas addition. After
      obtaining the desired PaCO2, the measurements were made. In the next experiment,
      we administered 2 different concentrations of epinephrine or phenylephrine
      solutions (1:2 x 10(6), 1:2 x 10(5)) through the window, and the measurement was
      made sequentially. The response of cerebral and spinal vasculature to change in
      PaCO2 was almost similar. Topical application of both drugs produced a
      significant constriction of spinal pial arterioles compared with the cerebral
      ones, while epinephrine but not phenylephrine constricted cerebral pial venules
      compared with spinal ones. These results suggest that the responses to
      vasoconstrictor of cerebral and spinal pial vessels are not similar, and high
      sensitivity of spinal arterioles to vasoconstrictors may possibly contribute to a
      risk of ischemic damage of the spinal cord.

PMID- 9028079
TI  - [The effects of vasoconstrictors on distribution of ischemic tissue flow in
      isolated perfused rat liver].
AB  - We studied the effects of ATP and epinephrine on distribution of ischemic hepatic
      tissue flow in the isolated perfused rat liver. Five minutes after clamping both
      the portal vein and hepatic artery, perfusion was started. Lidocaine was infused
      into the portal vein, and the concentration of lidocaine in hepatic outflow was
      measured with FPIA. The oxygen extraction ratio was also measured. Tissue surface
      blood flow was measured with laser-Doppler flowmetry. We measured the tissue flow
      at 2 points: one where flow was more than 10 ml.min-1.100 gm liver weight-1 (R),
      and the other where flow was less than 10 ml.min-1.100 gm liver weight-1 (P).
      After perfusion pressure had become stable, ATP or epinephrine was infused for 15
      minutes. Perfusion pressure increased, and tissue flow of R decreased
      significantly, while that of P increased (not significantly). The extraction
      ratio of lidocaine decreased significantly by epinephrine, and that of oxygen
      decreased (not significantly). We conclude that in the ischemic liver,
      vasoconstriction results in changes in the distribution of tissue blood flow and
      alters drug metabolism.

PMID- 9028080
TI  - [Effect of dibucaine and lidocaine on histamine release from mouse bone marrow
      derived cultured mast cells].
AB  - We examined the effects of dibucaine and lidocaine on histamine release from
      mouse bone marrow-derived cultured mast cells. The effects of these drugs on
      intracellular calcium were also monitored by assessing Fura-2 signals.
      Additionally, the inhibitory effects of lidocaine on IgE dependent and
      independent stimuli were examined. Though dibucaine induced histamine release and
      increases in intracellular calcium from mast cells dose-dependently, lidocaine
      did not. Lidocaine inhibited both the IgE-dependent and independent histamine
      release from mast cells in a dose dependent manner. However, the ability of
      lidocaine to inhibit the IgE-dependent response was greater. Lidocaine also
      inhibited increases in intracellular calcium to a greater extent after IgE
      dependent stimulation as compared with IgE-independent stimulation. The degree of
      the inhibition of histamine release by lidocaine appeared to parallel decreases
      in calcium mobilization.

PMID- 9028081
TI  - [Evaluation of neutrophil activation using elastase releasing capacity in vitro
      during perioperative period of esophagectomy].
AB  - Neutrophil activation is considered to play a major role in organ dysfunction
      after severe trauma. Major surgery like esophagectomy also induces various host
      responses including neutrophil activation and it may be responsible for
      postoperative complications. We measured neutrophil elastase releasing capacity
      in 14 patients undergoing esophagectomy to evaluate perioperative changes of
      neutrophil activation. Elastase releasing capacity was estimated by the fMLP
      induced elastase release from separated neutrophils in vitro and expressed as %
      increase of released elastase activity induced by 0.2 microM fMLP. Elastase
      releasing capacity was significantly increased from 28.6 +/- 17.7% after
      induction of anesthesia to 63.7 +/- 38.8% at 72 hours after induction, and
      decreased to 57.6 +/- 15.4% at 72 hours after induction. Elastase alpha 1
      antitripsin inhibitor complex showed no significant increase during perioperative
      period. Interleukin-6 showed a peak level 24 hours after induction and
      interleukin-8 was increased significantly 12 hours after induction and maintained
      the elevated level until 72 hours postoperatively. We concluded that the
      neutrophil activity was increased during the perioperative period of
      esophagectomy and the priming of neutrophil took place during extensive surgical
      intervention.

PMID- 9028083
TI  - [Examples of pitfalls in statistical analysis--5: Analysis of a multiple factor
      model].
AB  - When we analyze the effects of multiple factors, it is inadequate to repeat
      simple comparisons of the groups divided by a factor. The reasons for this are
      twofold, i.e., the total error rate of the study grows higher in proportion to
      the number of comparisons, and we cannot evaluate the relationships between the
      factors. It is reasonable in such a situation to use multivariate analyses which
      are developed to analyze multiple factor models, by changing the analytic point
      of view. In this article, I present an example to illustrate several types of
      mistakes which occur when we simply compare the two groups divided by one factor
      for other multiple factors, and explain the evaluation with correlation analysis
      and factor analysis.

PMID- 9028082
TI  - [Effect of amrinone and vagotomy on airway constriction in dogs: analysis by
      respiratory system impedance method].
AB  - Amrinone, a selective phosphodiesterase III inhibitor, is a positive inotropic
      agent with vasodilating effect which is attributable to an increase in cyclic AMP
      in vascular smooth muscle. Little is known about the effect of amrinone on airway
      mechanics. The purpose of this study was to clarify the bronchodilating effect of
      amrinone in dogs, when bronchoconstriction was induced by methacholine infusion.
      We also evaluated the effect of amrinone on bronchoconstriction in vagotomized
      dogs. To evaluate the effect of amrinone on respiratory function, the total
      respiratory system impedance was measured using forced oscillation method by
      imposing a random noise. The analysis was performed by dynamic models and a
      second-order system curve fitting. From the study, we conclude that amrinone 0.5
      mg.kg-1.1.0 mg.kg-1 or 2.0 mg.kg-1 attenuates methacholine-induced
      bronchoconstriction in a dose-related manner. In vagotomized dogs, amrinone also
      had the same effect on methacholine induced bronchoconstriction.

PMID- 9028084
TI  - [Anesthesiologists and information resources on the Internet].
AB  - The Internet connects computers around the world using the common protocol.
      Anesthesiologists are providing places on the Internet to exchange anesthetic
      information and share information resources, in the form of mailing lists and
      World Wide Web. They are also distributing anesthetic information to persons
      engaging in other medical services as well as to the general public. There are
      many information resources on the Internet that are useful for daily diagnosis
      and treatment, self-study, education and research by anesthesiologists.

PMID- 9028085
TI  - [Usefulness of alpha 2-adrenoceptor agonists and practical problems associated
      with their use in clinical anesthesia--II. Effects in regional anesthesia and
      analgesic effects for pain relief].
AB  - In the second part of this review, we summarized the effects of alpha 2
      adrenoceptor agonists (clonidine and dexamedetomidine) in regional anesthesia and
      pain control, and evaluated their usefulness as anesthetic adjuvants and
      analgesics in the clinical settings. In addition, we referred to practical
      problems associated with their use.

PMID- 9028086
TI  - [Postoperative pain relief for a patient with elective mutism by patient
      controlled analgesia].
AB  - We previously reported that intrathecal (i.t.) administration of morphine reduced
      postoperative pain in pediatric patients after spinal instrumentation for
      scoliosis (Cotrel-Dubousset method), and the i.t. administration of morphine
      before incision produced better pain relief than that given after the surgical
      procedure. In this study, we evaluated postoperative pain relief in a patient
      with elective mutism who had been given i.t. morphine 0.15 mg before surgery. The
      patient was scheduled to undergo patient controlled analgesia (PCA) intravenously
      with morphine after surgery. The grade of postoperative pain and incidence of
      side effects were assessed at 1, 2, 6, 12, 24, and 48 h after the operation. The
      pain was rated by means of a verbal numeric rating scale (0-3) and a visual
      analog scale (VAS) (0-100mm). The used morphine volume shown on a PCA device was
      evaluated at scheduled times. No patient developed hemodynamic instability or
      respiratory depression during the monitoring period. We conclude that PCA can be
      useful for the patient with elective mutism.

PMID- 9028087
TI  - [Aprotinin 2 million KIU reduces perioperative blood loss in patients undergoing
      primary total hip replacement].
AB  - We investigated consecutive patients undergoing primary total hip replacement
      surgery who were randomly assigned into two groups; those who received a blinded
      solution of aprotinin 2 million KIU (kallikrein inactivation units) (n = 11) and
      those who received an equivalent volume of normal saline placebo (n = 10)
      throughout the surgical procedure. Anesthesia and surgical techniques were
      standardized. All patients received spinal anesthesia combined with general
      anesthesia. There was no significant difference in blood loss during operation
      between the two groups. However, postoperative blood loss in the aprotinin group
      (284 +/- 155g, mean +/- SD) was significantly less compared with that in the
      control group (723 +/- 334g). Total blood loss in the aprotinin group (820 +/-
      255g) was also significantly less than in control group (1265 +/- 389g). We
      conclude that the use of aprotinin 2 million KIU during total hip replacement
      results in significantly less perioperative blood loss, especially during the
      postoperative period.

PMID- 9028088
TI  - [Anesthetic management of a pediatric patient with non-Fukuyama type congenital
      muscular dystrophy].
AB  - Non-Fukuyama type congenital muscular dystrophy (n-FCMD), a subtype of
      progressive muscular dystrophy (PMD), is a very rare autosomal recessive
      disorder. N-FCMD is characterized by severe and progressive motor weakness and
      atrophies of proximal muscles during the infant period. A 9-year-old boy with n
      FCMD underwent elective surgery for muscle release around the hip joints
      bilaterally. As many perioperative complications related with volatile
      anesthetics and muscle relaxants had been reported in the anesthetic management
      of PMD, these drugs were thought to be contraindicated in patients with n-FCMD.
      Because n-FCMD seemed to have very similar pathogenesis with PMD, caudal epidural
      block was chosen, supplemented with the administration of diazepam, pentazocine
      and nitrous oxide. The operation and anesthesia were conducted uneventfully. No
      complications occurred postoperatively.

PMID- 9028089
TI  - [Hemodynamic effects of amrinone combined with dopamine in patients undergoing
      living renal transplantation].
AB  - Systemic hypertension is a constant feature of chronic renal failure, mediated by
      renin and exacerbated by salt and fluid loading. Vascular atherosclerosis appears
      to accelerate in patients on long-term dialysis. Therefore, it is important to
      control hypertension and keep appropriate renal blood flow during living renal
      transplantation surgery. Amrinone, a phosphodiesterase inhibitor, produces
      vasodilation in arterial smooth muscle as well as venodilation in the capacitance
      bed. By increasing myocardial contractility it increases inotropic effect.
      Amrinone has potent inodilator effects because of its dual mechanism of action.
      The current study is aimed to compare hemodynamic effects between amrinone (3-5
      mg.kg-1.min-1) (AMR group, n = 4) and nitroglycerin (0.3-1.0 mg.kg-1.min-1) (NTG
      group, n = 5), combined with dopamine (3-5 mg.kg-1.min-1) in nine patients
      undergoing living renal transplantation. Increase in cardiac index in AMR group
      was significantly larger than that in NTG group. Values of systemic and pulmonary
      vascular resistance in AMR group were significantly smaller than those in NTG
      group. No significant difference was found in renal function in the post
      operative period.

PMID- 9028090
TI  - [Three patients with Gilbert's syndrome associated with constitutional excretory
      defect of indocyanine green].
AB  - We routinely perform, as a preoperative liver function test, the indocyanin green
      (ICG) test in patients scheduled for operations under general anesthesia. Doubts
      have been raised, however, concerning the necessity for this test, since no
      abnormalities have ever been detected by it. Nonetheless, we noted a high level
      of ICG retention and a slight increase in indirect bilirubin in 3 patients, and
      further investigation led to a diagnosis of Gilbert's syndrome accompanied by
      constitutional impairment of ICG excretion. This syndrome can be associated with
      perioperative jaundice in patients with malnutrition and those who received
      halothane, morphine, or some other agents. Although the indirect bilirubin level
      increased briefly after surgery, no other abnormalities occurred in the 3
      patients. Since this syndrome is asymptomatic and is detected incidentally, the
      preoperative ICG test was considered to be useful.

PMID- 9028091
TI  - [Intraoperative continuous epidural lidocaine combined with preoperative
      administration of epidural morphine for post-hepatectomy pain relief].
AB  - In a randomized double-blind study, the use of continuous epidural lidocaine
      during surgery combined with preoperative epidural morphine was compared with
      that of preoperative epidural morphine alone for postoperative analgesia in 20
      patients undergoing hepatectomy. Morphine 2 mg was administered through a
      catheter inserted epidurally at T10-11 before surgery, followed by continuous
      epidural administration of 1% lidocaine 5ml.h-1 in group Lid (n = 10) or normal
      saline 5ml.h-1 in group NS (n = 10) during surgery. Anesthesia was maintained
      with N2O-O2-isoflurane in both groups. On admission to the ICU, the visual analog
      scale score (VAS; mm) was 20 +/- 7 (mean +/- SE) in group Lid and 38 +/- 10 in
      group NS, and the number of patient with VAS < or = 30 was 9 in group Lid and 4
      in group NS; these differences were significant (P < 0.05). Pain score during
      mobilization in group Lid was significantly lower than that in group NS (P <
      0.05). All patients in both groups had adequate analgesia for the remainder of
      their stay in the ICU. No patient had any serious adverse effect. We conclude
      that continuous epidural administration of lidocaine during hepatectomy combined
      with administration of epidural morphine just before surgery results in better
      pain relief during the early postoperative period than that obtained with
      epidural morphine alone, and is without serious side effects.

PMID- 9028092
TI  - [A case of life-threatening anaphylactoid reaction caused by povidone-iodine].
AB  - A 64 year-old man developed life-threatening anaphylactoid reaction caused by
      povidone-iodine during induction of anesthesia for elective coronary artery
      bypass graft surgery. While he had a history of cardiac arrest caused by iodine,
      he could tolerate contrast material and povidone-iodine for pre-operative
      coronary angiography with pretreatment of H1 and H2 receptor blockades and
      methylprednisolone. During the operation and postoperative care we could manage
      cardiac failure by continuous monitoring of cardiac output (CCO) using pulsed
      thermodilution method. We recommend prophylactic use of H1 and H2 receptor
      blockades for surgical patients who may be at risk for anaphylaxis or
      anaphylactoid reaction.

PMID- 9028093
TI  - [The effect of nicardipine hydrochloride upon the pulmonary arterial pressure].
AB  - This study examines the effects of induced hypotension with intravenous
      administration of nicardipine hydrochloride (NIC) upon pulmonary arterial
      pressure (PAP) undergoing modified radical mastectomy with neuroleptanesthesia
      (NLA-group; 3 cases) and inhalation anesthesia (N2O+ isoflurane; GOI-group; 3
      cases). Systolic arterial pressure was reduced and maintained at 80 mmHg. During
      and after induced hypotension in NLA-group, heart rate (HR), cardiac index,
      pulmonary arterial pressure (PAP) increased remarkably. On the other hand,
      systemic vascular resistance index was reduced. In GOI group, no significant
      changes were seen in PAP. The acceleration of the autonomic baro-reflex induced
      by decreased blood pressure produced by NIC may be depressed under anesthesia to
      initiate this difference in response of HR to NIC. The data indicate that this
      depressive effect of NLA on this reflex is weak, and NIC is a potent systemic
      vasodilator with hyperdynamic hemodynamic effects in addition to an increase in
      right ventricular function, and PAP was increased.

PMID- 9028094
TI  - [Epidural anesthesia for herniorrhaphy in a patient with severe dilated
      cardiomyopathy (DCM) under pimobendan control].
AB  - A 60-year-old man with severe DCM was scheduled for a herniorrhaphy under
      epidural anesthesia using fentanyl. Three months prior to operation, the patient
      suffered heart failure associated with life-threatening ventricular arrhythmia.
      The former was successfully treated with pimobendan as the main constituent of
      medication, but the latter was not responsive to various antiarrhythmic drugs
      with the exception of aprindine. On the day of operation and for two days
      postoperatively, pimobendan was administered daily. A sudden drop in systemic
      blood pressure and central venous pressure (CVP) during anesthesia, as well as
      the tendency to hypotensive status in the postoperative period were well
      regulated with continuous infusion of dopamine and dobutamine via CVP catheter
      probably due to the effect of up-regulation of pimobendan, together with
      adjustment of the volume of intravenous fluids. No dangerous ventricular
      arrhythmia were observed. Thereafter the patient made uneventful progress and was
      discharged on the 8th postoperative day.

PMID- 9028095
TI  - [A case of crush syndrome resulting from continuous compression of the upper arm
      by automatically cycled blood pressure cuff].
AB  - We report a case of crush syndrome (rhabdomyolysis) resulting from the prolonged
      compression of the inadvertently inflated blood pressure cuff around her upper
      arm. A 61-yr-old woman had undergone total gastrectomy, splenectomy and
      cholecystectomy for gastric cancer. At the end of the surgery lasting for 5 hrs
      40 mins, we found the right upper arm extremely swollen with cyanotic petechiae
      beyond the inflated cuff. Failure of deflation of the automatically cycled blood
      pressure cuff was strongly suspected as a cause. She complained numbness and
      ardor on her hand with motor nerve disturbance and plasma CPK level was elevated.
      Diuretics were given and fluids were infused vigorously to prevent the renal
      failure, and continuous cervical epidural block was instituted to increase the
      blood flow to the injured arm. Prostaglandin E1 and ulinastatin (a protease
      inhibitor) were also effective for recovery from the crush syndrome. One month
      later she was discharged home accompanied with a slight numbness on the arm.
      Attention should be paid to deflation of the automatically cycled blood pressure
      cuff during anesthesia.

PMID- 9028096
TI  - [Cervical spine movement during orotracheal intubation using the McCoy
      laryngoscope compared with the Macintosh and the Miller laryngoscopes].
AB  - The movement of cervical spine during orotracheal intubation was compared using
      the McCoy, Macintosh or Miller laryngoscope blade. Twenty ASA 1-2 patients
      requiring tracheal intubation were studied. Following induction of anesthesia and
      obtaining muscle relaxation, the cross-table lateral X-ray was taken before and
      during laryngoscopy using three types of laryngoscopes. Degree of cervical spine
      movement was evaluated by measuring the distance between the spinous processes of
      C1 and the occiput, and the amount of displacement of C1 and C5 against C3 by
      tracing on each films. The results indicated that delta C1-occiput was larger and
      delta C1 + C5 smaller with the McCoy laryngoscope compared with the others. The
      use of the McCoy laryngoscope results in less cervical spine movement during
      laryngoscopy and therefore should be of particular benefit in the presence of
      cervical spine instability as well as in the normal patients.

PMID- 9028097
TI  - [Ophthalmology in Japan and the foundation of the Ophthalmological Society].

PMID- 9028098
TI  - [Some aspects of research and development in diagnosis and treatment of central
      serous chorioretinopathy in Japan].

PMID- 9028099
TI  - [A tendency of the biochemical cataract research].

PMID- 9028100
TI  - [Studies on kinetic viscoelasticity of slow muscle fibers--1. Tension, fatigue
      resistance and stiffness in rabbit extraocular muscles].
AB  - To evaluate the mechanical properties of the slow fibers and fast fibers which
      make up the extraocular muscle, I studied the contractibility and viscoelasticity
      properties of the superior rectus muscle (SR) and the retractor bulbi muscle (RB)
      of rabbits. Eighteen to nineteen percent of whole muscle tension was produced by
      slow fibers in SR and 1 to 5% by those in RB. After long continuous contraction,
      fatigue-resistant fibers left residual tension in SR, but the tension was almost
      entirely absent in RB. The frequency response method was used to examine kinetic
      viscoelasticity. The muscle was stretched sinusoidally, with an amplitude of 1 mm
      at 20 Hz in Lmax. The tension amplitude to sine wave vibrations during tetanus
      (P) and resting (Po) were then examined. The dynamic stiffness ratio (P/Po) was
      higher in SR (3.1) than in RB (2.0). I suggest that the viscoelasticity of the
      activated cross bridge is greater in slow fibers than in fast fibers.

PMID- 9028101
TI  - [Indocyanine green infrared fluorescence angiography and histopathological
      correlation in experimental choroidal circulatory disturbance. Report 1].
AB  - We performed an experimental study on choroidal circulatory disturbance to
      clarify basic problems about interpretation of retino-choroidal lesions in
      indocyanine green fluorescence angiography (ICG angiography). We severed all of
      the posterior temporal ciliary arteries, to produce choroidal circulatory
      disturbance. Fluorescein angiography and ICG angiography were performed using
      scanning laser ophthalmoscope immediately, and 2 days after occlusion. These
      findings were compared with histopathological findings from the same specimen.
      Immediately after occlusion, choroidal vessels were filled with the red blood
      cells in the lesion that showed hypofluorescence in both types of angiography.
      Two days after occlusion, the fundus had a grayish white edematous appearance
      which was similar to choroidal infarction. The retinal pigment epithelial cells.
      (RPEs) in infarcted lesion progressed to liquefied necrosis. Fluorescein
      angiography showed hyperfluorescence in the lesion, and ICG angiography showed
      hypofluorescence in the early phase, but hyperfluorescence at the margin of the
      lesion in the late phase. This result showed that damaged RPEs were stained by
      ICG dye. In reading ICG angiography, we have to consider that the ICG angiogram
      is greatly modified by the condition of the RPEs.

PMID- 9028102
TI  - [Early ocular changes in a tree shrew model of diabetes].
AB  - We developed a tree shrew model of diabetes using streptozotocin (STZ), and
      studied early ocular changes of diabetes (after one week of diabetes) by
      fluorophotometry. STZ was injected intraperitoneally at doses of sixty to 400
      mg/kg body weight. Animals injected with more than 300 mg/kg of STZ developed
      diabetes. Corneal autofluorescence was significantly increased one week after STZ
      injection. These changes may be related to impairment of the ocular homeostatic
      mechanisms due to the onset of diabetes. Using this model, we might be able to
      obtain diabetic ocular impairment data closer to human data than in previous
      models of diabetes, because tree shrews are primates.

PMID- 9028103
TI  - ['Ischemic tolerance' in ischemia-reperfusion injury in the optic nerve in rats].
AB  - Brief ischemia caused by high intraocular pressure induced tolerance to
      subsequent ischemia-reperfusion injury in rats. Male Wistar rats were subjected
      to 15 minutes of ischemia. This ischemic injury did not show distinct axonal
      damage in the optic nerve in electron microscopy. 1, 2, 4, 7, and 14 days after
      the first 15 min ischemia, the rats were subjected to a second ischemia for 45
      minutes (ischemic tolerance). After 1 week, the rats were perfusion fixed and the
      optic nerves were processed for light and electron microscopy. Samples of the
      axonal density in the central optic nerve 2 mm behind the lamina cribrosa were
      observed and counted an electron micrographs. In axonal morpometric findings, 2
      days and more after brief ischemia, the damage was lessened more than after 45
      minutes ischemia (control) and the difference was significant. This 'ischemic
      tolerance' induced by brief ischemia might be considered the same stress as brain
      ischemia-reperfusion injury.

PMID- 9028104
TI  - [Reconstruction of the neuroretina from embryonic chick retinal cells in floating
      culture and the effect of growth factors].
AB  - We observed the three dimensional structure of cellular aggregates formed from
      chick retinal cells in a floating culture system for 2 months. The aggregated
      cells partially mimicked the structure of the retina and showed differentiation
      of photoreceptor cells and Muller cells with numerous synapses.
      Immunohistochemical studies showed the number of anti-rhodopsin positive cells
      increasing over time. In the long-term culture, increasing anti-crystalline
      positive cells appeared late in the culture, indicative of differentiation of
      lens epithelial cells. Nerve, epidermal, and basic fibroblast growth factors, and
      co-culture with retinal pigment epithelial cells stimulated to some degree the
      growth of dendrites in retinal cellular aggregates. Epidermal growth factor, in
      particular, promoted the production of rhodopsin in photoreceptor cells. Retinal
      cellular aggregates in a floating culture system could be used to examine the
      effect of various factors on differentiation of the neuroretina.

PMID- 9028105
TI  - [DNA damage and the mechanism following UV-B irradiation in lens epithelial
      cells].
AB  - DNA damage and its mechanism following ultraviolet-B (UV-B) irradiation were
      investigated in quantifying DNA strand break in bovine lens epithelial cells. In
      contrast, the DNA relative migration distance was as little as 0.14 +/- 0.34
      (mean +/- standard deviation) in controls, 1.10 +/- 0.89 at 0.5 kJ/m2
      irradiation, 1.61 +/- 1.05 at 1 kJ/m2, 4.65 +/- 1.18 at 3 kJ/m2, and 6.10 +/-
      0.93 at 5 kJ/m2. The degree of DNA strand break increased with the intensity of
      the UV-B irradiation. 1.10-phenanthroline, an iron ion chelator, significantly
      reduced DNA strand break. These results suggest that the Fenton reaction might
      participate in DNA damage of normal lens epithelial cells following UV-B
      exposure.

PMID- 9028106
TI  - [Histochemical studies on the separation of the lens vesicle].
AB  - We studied histologically the changes and distribution patterns of
      glycosaminoglycan molecular species during the separation of the lens vesicle in
      the mouse. Embryos were obtained by sacrificing pregnant mice of the Jcl: ICR
      strain on day 10.5 and 11 of pregnancy. Serial frontal sections were stained with
      hematoxylin-eosin and a sensitized high iron diamine method. To identify
      glycosaminoglycan molecular species in tissues, enzyme digestion (double
      digestions with chondroitinase B and testicular hyaluronidase) and chemical
      modification (nitrous acid treatment) were performed in combination with the
      sensitized high iron diamine method. Before separation of the lens vesicle, the
      glycosaminoglycan molecular species, identified in the basement membrane of the
      presumed corneal epithelium and intercellular matrices between the presumed
      corneal epithelium and lens vesicle, were chondroitin sulfate A/C and B, and
      those in the lens capsule were chondroitin sulfate A/C. After separation of the
      lens vesicle, heparan sulfate emerged in the basement membrane of the presumed
      corneal epithelium and intercellular matrices between the presumed corneal
      epithelium and lens vesicle. These results are thus taken to indicate that the
      changes and distribution patterns of glycosaminoglycan molecular species play an
      important role during separation of the lens vesicle.

PMID- 9028107
TI  - [Evaluation of conjunctival epithelial damage in dry eye].
AB  - Using sulphorhodamine B, which is highly sensitive in detecting damaged ocular
      surface epithelium, we evaluated conjunctival epithelial damage in dry eye
      patients. The subjects were 99 eyes of 50 dry eye patients (41 eyes of 21
      patients with Sjogren's syndrome and 58 eyes of 29 keratoconjunctivitis sicca
      patients without Sjogren's syndrome). We also investigated the relation between
      sulphorhodamine B and fluorescein staining in ocular surface epithelium. The
      conjunctival epithelial damage stained with sulphorhodamine B showed a high
      correlation with corneal epithelial damage stained with fluorescein. In addition,
      conjunctival damage in Sjogren's syndrome tended to be more severe than in
      patients without Sjogren's syndrome.

PMID- 9028108
TI  - [Distribution of cell adhesion glycoproteins in the human retrobulbar optic
      nerve].
AB  - We examined the immunohistochemical distribution of six types of cell adhesion
      glycoproteins in the human retrobulbar optic nerve. The pial septa had laminin
      and entactin on the surface at the border with the optic nerve fibers, and
      fibronectin and vitronectin were distributed in the stroma of the septa. Some
      tenastin was also detectable both on the surface and in the stroma of the septa.
      Thrombospondin was associated with capillaries within the stroma. The surface of
      the arachnoid membrane, the pia mater, and the dura mater was covered by laminin
      and entactin. Diffuse staining with antifibronectin antibody was seen in all
      these meningeal tissues, but vitronectin showed a fine fibrillar appearance in
      these tissues. No significant staining could be found for tenastin.
      Thrombospondin showed only faint staining on the capillaries of the pia mater and
      the dura mater. These findings can provide clues for the discussion of how the
      extracellular matrix works and what roles it plays in disorders involving the
      retrobulbar optic nerve, such as optic neuritis and glaucoma.

PMID- 9028109
TI  - [Ocular complications of atopic dermatitis].
AB  - We examined the frequency and types of ocular complications that developed in 560
      eyes of 280 patients with atopic dermatitis at the Department of Dermatology,
      Tokyo Medical College Hospital. Mild ocular involvement included blepharitis in
      294 eyes (52.5%), conjunctivitis in 221 eyes (39.5%), and superficial punctate
      keratopathy in 65 eyes (11.6%). More serious ocular complications leading to
      decreased visual function occurred in 133 eyes (23.8%) that developed lens
      opacities, and 34 eyes (6.0%) that developed retinal break or retinal detachment.
      Because of the presence of abnormalities in the peripheral retina, we believe
      that a pathogenic factor may have been present in the vitreous of these atopic
      dermatitis patients. Many of our patients with atopic dermatitis had serious
      ocular complications in the absence of ocular symptoms. Thus it is important to
      conduct a thorough ophthalmological examination in the early period of disease in
      atopic dermatitis patients, both for the management of early but serious ocular
      complications, as well as for the preservation of visual function.

PMID- 9028110
TI  - [Ultrasound biomicroscopic observation of the anterior eye segment in a
      sclerocornea and a microcornea].
AB  - We observed the anterior segment of eyes in one case of sclerocornea and one case
      of microcornea using an ultrasound biomicroscope. The sclerocornea was the
      peripheral type. The contrast in the image of ultrasound biomicroscopy changes
      from low to high density in proportion to the optical opacity at the peripheral
      portion of the cornea. There was no abnormality in the anatomical figures of the
      anterior chamber angle in ultrasound biomicroscopic findings, which gave
      significant information in the cataract surgery. The patient with microcornea had
      horizontal nystagmus, partial coloboma of the iris, choroidal coloboma, and
      cataract in both eyes. We observed the iris tissue in all the meridians in the
      ultrasound biomicroscopic pictures. Ultrasound biomicroscopy is a promising
      procedure for examining the anterior segment of eyes with corneal opacity.

PMID- 9028111
TI  - [Study of choroidal vascular lesions in central serous chorioretinopathy using
      indocyanine green angiography].
AB  - We performed fluorescein and indocyanine green (ICG) angiographies in 56 patients
      with central serous chorioretinopathy, and studied the choroidal lesions. In the
      early phase, choroidal filling with ICG was delayed in 77% in the area including
      focal leakage. Hypofluorescent findings around the site of focal leakage
      persisted through the phase in 23%, and we think this finding was caused by
      filling defect of the choriocapillaris. In the late phase, choroidal tissue
      staining by ICG was present in 82% in the area including focal leakage. Multiple
      areas of choroidal staining were also present in unaffected areas in 43% and in
      62% of fellow eyes. Choroidal tissue staining by ICG was revealed in 48% in the
      area of choroidal filling delay, and this finding persisted after focal leakage
      had disappeared following photocoagulation. We think this finding was caused by
      choroidal vascular hyperpermeability. These findings suggest that choroidal
      circulatory disturbance and choroidal vascular hyperpermeability play a causative
      role in damage to the retinal pigment epithelium in central serous
      chorioretinopathy.

PMID- 9028112
TI  - [Lectin histochemistry of the glycoconjugates in conjunctival goblet cells].
AB  - The distribution of O- and N-linked glycoconjugates in human conjunctival goblet
      cells was examined histochemically using biotinylated and fluorescence-labeled
      lectins simultaneously. Both peanut agglutinin and Erythrina cristagalli
      agglutinin, specific for O- and N-linked sugar chains, respectively, bound to the
      same goblet cell, which demonstrated that a conjunctival goblet cell produces and
      contains both types of glycoconjugates. Maackia amurensis lectin II, specific for
      sialic acid alpha 2, 3 galactose, bound to the goblet cells, while Sambueus nigra
      agglutinin, specific for sialic acid alpha 2, 6 galactose, did not. This
      observation suggested that the terminal galactosyl residue of the glycoconjugates
      is alpha 2, 3-sialylated in the human conjunctival goblet cells.

PMID- 9028113
TI  - [An immunohistochemical study on glycosaminoglycans distribution in the
      trabeculum of congenital aniridia].
AB  - Distribution of glycosaminoglycans in the trabecular tissue was
      immunohistochemically investigated in 7 congenital aniridia eyes of 5 patients
      aged 0 to 43 days. Paraffin sections of each specimen were immunohistochemically
      stained with antibodies to chondoroitin (clone 1-B-5), chondoroitin-1-sulfate (2
      B-6), chondoroitin-6-sulfate (3-B-3), dermatan sulfate (6-B-6), and keratan
      sulfate (5-D-4). The trabecular meshwork and Schlemm's canal in all eyes were
      absent or not well differentiated. The cornea, trabecular tissue, and iris stroma
      were negative for chondoroitin immunostaining but positive for chondoroitin-4
      sulfate, chondoroitin-6-sulfate, dermatan sulfate and keratan sulfate
      immunostaining. In the normal anterior segment tissue keratan sulfate is present
      in the cornea, trabecular tissue, and iris at the fetal stage, and disappears
      from the iris at the neonatal stage. These findings suggest that the persistence
      and/or abnormal distribution of keratan sulfate in the anterior segment may play
      a role in the pathogenesis of congenital aniridia.

PMID- 9028114
TI  - [A case of paraneoplastic retinopathy with serum antibody against retinal soluble
      70 kDa protein].
AB  - We report a case of paraneoplastic retinopathy in a patient who was found to have
      small cell carcinoma of the lung and was shown to have serum antibody against
      retinal soluble 70 kDa protein. A 71-year-old woman visited her ophthalmologist
      for gradual visual loss in both eyes. Although she underwent uncomplicated
      cataract surgery in her left eye, she was referred to our hospital because of
      progressive visual deterioration in November 1994. On admission, her corrected
      visual acuity was 0.3 OD and hand motion OS. Funduscopic examination showed
      narrowing retinal arteries, pigment epithelial mottling in the posterior retina
      bilaterally, and optic disc pallor in the left eye. An electroretinogram
      demonstrated marked reduction in the a and b waves. Bilateral central scotomas
      were detected by kinetic perimetry. We pursued further examination for systemic
      disease, and identified increased serum level of neuron specific enolase and
      radiographically abnormal shadow in the chest. Transcutaneous needle biopsy of
      the mediastinum confirmed small cell carcinoma. In western blot analysis the
      patient's serum reacted strongly with soluble retinal proteins of 70 kDa
      molecular weight, although the 26 kDa CAR antigen was not labeled. This patient
      was diagnosed as having paraneoplastic retinopathy due to small cell carcinoma
      and unusual serum protein which responded to an antigen with a molecular weight
      of 70 kilodaltons.

PMID- 9028116
TI  - [Pulmonary function during exercise before and after radical esophagectomy for
      esophageal cancer].
AB  - Since the postoperative long-term evaluation for thoracic esophageal carcinoma
      had not been sufficient by a conventional respiratory function test alone,
      investigation was carried out by observing the changes in motor tolerance. The
      subjects were selected of 50 cases who elapsed more than 3 months before and
      after the operation among the cases who had been undergone radical operations
      with right thoracotomy and laparotomy for thoracic esophageal carcinoma; and then
      all of the subjects were subjected to a conventional respiratory function test
      and a respiratory movement loading test. Furthermore, investigation by use of
      multivariate analysis (Quantification: Class 1) was conducted for the factors
      relating to the depression of respiratory movement. For loading the movement,
      bicycle-type ergometer were employed, and a graded gradual-increase loading
      method was adopted. With the general respiratory function test, vital capacity
      was depressed from a preoperative average value of 2.1 +/- 0.4 (1/m2) to a
      postoperative average value of 1.6 +/- 0.3 (1/m2) showing a depressing trend
      being significant to a postoperative condition (p < 0.0001), and no significant
      postoperative difference was observed for FEV 1.0%. Even in such a condition, no
      significant depression was observed for oxygen intake at resting, but the maximum
      oxygen intake showed a significant depression (p < 0.0001) from a preoperative
      average value of 22.3 +/- 5.0 to a postoperative average value of 19.3 +/- 4.1
      ml/min/kg. The maximum carbon oxide evacuation showed a significant depression (p
      < 0.0001) after operation. The ventilation quantity in a course of movement
      showed a depressing trend after operation, with be number of respiration in an
      increasing trend, showing a shallow-but-quick respiratory pattern. Mobility
      restriction due to circulation factors was not observed, and also the nutrition
      before and after operation did not show any significant difference in the blood
      examination. But the lactic acid during movement showed a significant increase
      after operation. As described above, it is considered that a pattern of
      restrictive impairment at resting increased an oxygen equivalent resulted from
      depression of oxygen intake by the movement, an increase in dead space
      ventilation rate for minute ventilation at movement, and a shallow-but-quick
      respiratory pattern have caused aggravation of the ventilation efficiency, which
      finally led to the interruption of movement. In a long-term period, as clinical
      factors relating to those, cigarette smoking, nutrition before operation, age,
      and postoperative radiation therapy are concerned, which were thus considered the
      key factors in considering the postoperative long-term QOL. Nutrition and
      rehabilitation by continuous muscle training is necessary to improve the long
      term QOL, after radical esophagectomy.

PMID- 9028115
TI  - [Detection of mycobacterial DNA with polymerase chain reaction in eye discharge
      and gastric juices in a case of scleritis].
AB  - We report a case of mycobacterial scleritis in which prompt diagnosis was made by
      the detection of mycobacterial DNA with polymerase chain reaction (PCR) in eye
      discharge and gastric juices, when conventional tests were negative. A 77-year
      old woman who had a past history of pulmonary tuberculosis visited the outpatient
      clinic of Tokai University Hospital complaining of pain in her right eye. She was
      diagnosed as having scleritis and uveitis. There were no indications of active
      tuberculosis. We examined the gastric juices, sputum, and eye discharge by
      microscopy, culture, and PCR for detection of mycobacterium. The results of
      microscopy and culture were negative, but with PCR we detected atypical
      mycobacterium in eye discharge and gastric juices. After oral treatment with
      antituberculosis agents, the patient's eye symptoms disappeared. Detecting
      mycobacterial DNA with PCR could be useful for early diagnosis of mycobacterial
      scleritis, so that treatment with antituberculosis agents could be started.

PMID- 9028117
TI  - [The study of urgent pulmonary resections for lung cancer accompany with
      pneumonia].
AB  - We studied 10 lung cancer patients with pneumonia insusceptible of conservative
      treatment. All patients underwent urgent pulmonary resection to control their
      pneumonia induced by the tumor and to cure the cancer. The causes of pneumonia
      were bronchial obstruction by the tumor itself or aspiration of the tumor
      necrosis. The patients comprised 9 men and 1 women. The age range was 37 to 72
      years with a median age of 57 years. There were obstructive pneumonia in 3
      patients and aspiration pneumonia in 7 cases. The average size of tumor was about
      4.7 and 7.5 cm, respectively. The histological type of lung cancer was squamous
      cell carcinoma in 6 and adenocarcinoma in 4. There were 1 stage 1,1 stage IIIA
      and 3 stage IIIB tumors. Lobectomy was performed in 8 patients and pneumonectomy
      in 2 patients. Nine patients underwent the operation under one-lung ventilation.
      A median period of preoperative administration of antibiotics was 6.2 days. The
      curative operation for lung cancer was performed in 3 patients and non-curative
      operation in 7 patients. Postoperative complications were pneumonia in 2,
      subcutaneous abscess in 2 and arrhythmia in a case of pneumonectomy. All non
      curative patients died in 5 years, but two curative patients survived long time
      for 31 and 75 months, respectively. We performed urgent pulmonary resection for
      lung cancer patients to cure fatal pneumonia and cancer. There were no hospital
      death. Urgent pulmonary resection could prevent early death caused by fatal
      pneumonia by tumor itself.

PMID- 9028118
TI  - [Reoperation for malfunction of Ionescu-Shiley bovine pericardial bioprosthetic
      valves in the mitral position--special consideration with emergency operation].
AB  - Sixty-eight patients have had mitral valve replacement with Ionescu-Shiley bovine
      pericardial bioprosthesis from 1981 to 1984. Thirty five patients were required
      reoperation due to primary tissue failure of the bioprosthesis, 10 (28.6%) were
      on emergency basis and 25 (71.4%) were on elective. Hospital deaths were two
      (20.0%) on emergency and four (16.0%) on elective. Clinical features of emergency
      cases were as follows: progressive congestive heart failure in eight, severe
      hemolysis with massive hemoglobinuria in eight and acute renal failure in four.
      Cusp tears were observed in all valves, 8.1 +/- 1.5 mm in emergency group and 4.2
      +/- 3.6 mm in elective group. Neointimal ingrowth over Dacron cloth of the inner
      surface of the stent was absent in 29 valves (89.2%). Calcification was observed
      in seven valves, however these were not dominant causes of primary tissue
      failure. Clinical symptoms were correlated with structural deterioration of
      explanted valves. Structural deterioration of the bioprosthesis may occur
      suddenly and progressively. Our experience demonstrated that life-threatening
      prosthetic valve failure may occur with a relatively high incidence and that
      careful follow-up is needed for Ionescu-Shiley bovine pericardial bioprosthesis.

PMID- 9028120
TI  - [Effectiveness of continuous pulmonary perfusion during total cardiopulmonary
      bypass to prevent lung reperfusion injury].
AB  - The oxygen free radicals and the interaction between neutrophils and endothelium
      have been implicated in the pathogenesis of lung injury associated with
      cardiopulmonary bypass (CPB), and in the setting of total CPB, the ischemia
      reperfusion injury has been suspected as the mechanism of lung injury. To prevent
      this reperfusion induced lung injury, we performed continuous pulmonary perfusion
      during total CPB. We studied 26 infants less than 1 year of age who underwent
      patch closure of ventricular septal defect. Intermittent mechanical ventilation
      (5/min) and continuous perfusion of pulmonary artery (30 ml/kg/min) were
      performed during total CPB in 7 infants (Group P). Whereas 19 infants underwent
      ordinary CPB (Group N). PaO2/FiO2 ratio was employed for the predictor of lung
      injury and was calculated before and after CPB. PaO2/FiO2 ratio decreased from 3
      to 12 hours after CPB and then increased by 24 hours after CPB in both groups.
      The lowest PaO2/FiO2 ratio measured at 12 hours after CPB correlated with age and
      body weight at operation (Spearman's correlation coefficient, 0.59; p = 0.01 and
      0.61; p = 0.009, respectively) and strongly correlated with preoperative Rp/Rs
      ratio (-0.73; p = 0.003). PaO2/FiO2 ratio, however, did not correlate with
      duration of CPB and aortic cross clamping, preoperative Pp/Ps and Qp/Qs ratio in
      group N. PaO2/FiO2 ratio of group P at 3, 6, and 12 hours after CPB were higher
      than those of group N, although there were no significant difference When
      analysis was made on the infants with high pulmonary vascular resistance
      (preoperative Rp/Rs ratio > or = 0.1), PaO2/FiO2 ratio of group P (n = 6) at 3, 6
      and 12 hours after CPB were higher than those of group N (n = 11), and the
      difference was statistically significant at 12 hours after CPB (291.1 +/- 15.5
      versus 199.6 +/- 27.0, p = 0.027. These results implicate that young age, low
      body weight and especially high pulmonary vascular resistance were incremental
      risk factor of lung injury after CPB and, furthermore, ischemia reperfusion
      injury can be the initiating factor of lung injury. The results also suggest that
      continuous pulmonary perfusion during total CPB is an effective mean to prevent
      lung injury particularly for the infants with high pulmonary vascular resistance.

PMID- 9028119
TI  - [Effects of ischemic preconditioning on the recovery of myocardial function after
      unprotected ischemia and cardioplegia in the isolated and crystalloid perfused
      rat hearts].
AB  - Preconditioning with repetitive brief periods of ischemic (IPC) is known to
      induce myocardial protection against a subsequent more prolonged period of
      ischemia. We investigated whether IPC can offer similar beneficial effects on
      myocardial function after cardioplegic preservation in isolated and crystalloid
      perfused rat hearts. IPC was produced by 5 periods of 1 min ischemia followed by
      5 min reperfusion before 25 min of unmodified ischemia or 40 min of cardioplegia.
      IPC had no significant effect on the time to contractile arrest (control: 211 +/-
      27 sec, IPC: 240 +/- 32 sec) after unmodified ischemia, while the time to
      electrical asystole was significantly (p < 0.05) shortened by IPC (676 +/- 107
      sec) compared to control (1021 +/- 197 sec). However, rapid contractile arrest
      concomitant with electrical asystole was induced by infusion of St. Thomas'
      Hospital solution in control as well as in IPC-treated hearts without a
      significant intergroup difference (control: 33 +/- 7 sec, IPC 39 +/- 9 sec).
      Although myocardial ATP was significantly reduced by IPC, IPC-treated hearts
      showed a significantly higher ATP level after 25 min of unprotected ischemia.
      Accumulation of myocardial lactate after 25 min of unprotected ischemia was
      significantly (p < 0.05) inhibited by IPC. However, the levels of myocardial ATP
      and lactate after 40 min of cardioplegia were comparable between control and IPC
      treated hearts. Left ventricular developed pressure (LVDP) at 30 min reperfusion
      after unprotected ischemia was significantly improved by IPC, while the recovery
      of LVDP at 30 min reperfusion after cardioplegia was comparable between control
      and IPC-treated hearts. The onset of ischemic contracture, i.e., a rise of left
      ventricular end-diastolic pressure (LVEDP), was significantly accelerated and its
      magnitude was significantly greater in IPC-treated hearts during unprotected
      ischemia and also during cardioplegia. However, a significant decrease of LVEDP
      during reperfusion compared to control hearts was observed only after unprotected
      ischemia. The amounts of creatine kinase (CK) released during 30 min reperfusion
      after unprotected ischemia was significantly greater in control than in IPC
      treated hearts, but there was no significant difference in CK release between
      control and IPC-treated hearts during reperfusion after cardioplegia. These
      results suggest that IPC-induced cardioprotection may be induced via inhibition
      of anaerobic energy metabolism through a negative chronotropic effect during
      unprotected ischemia, but such a beneficial effect is dissipated with
      cardioplegia by which rapid electrical asystole is induced. It is, therefore,
      concluded that IPC may not provide additional myocardial protection over
      conventional hyperkalemic cardioplegia.

PMID- 9028121
TI  - [Comparison of left ventricular pressure-volume loops measured by two-dimensional
      echocardiography and a conductance catheter].
AB  - A left ventricular pressure volume loop (PV loop) is useful not only in
      evaluating cardiac function, but also in predicting the postoperative hemodynamic
      state. There are two methods available for the intraoperative measurement of a PV
      loop: a conductance catheter and two-dimensional echocardiography. Although the
      accuracy of conductance catheter is well established for the measurement of
      ventricular volume, however, the accuracy of echocardiography remains
      controversy. This paper describes the relationship of parameters including
      volumes and Emax calculated with each method. Six patients who underwent open
      heart surgery were included in this study. Comparison of the absolute volumes at
      four points at the corners of the PV loop showed a Pearson's correlation
      coefficient of 0.62 (p-value < 0.01). In comparison with the relative volumes at
      four points which reflect the preoperative to postoperative change ratio, the
      correlation coefficient was 0.74 (p < 0.01). The correlation coefficients were
      0.76 (p = 0.16) and 0.63 (p = 0.29) for the ratio of the end-diastolic and end
      systolic volume respectively. Each preload-varying "Emax: out" (r = 0.84, p <
      0.01) were highly correlated. As a predictor of cardiac oxygen consumption, each
      PVA (r = 0.84, p < 0.01) was highly correlated. We conclude that the measurement
      of left ventricular volume using two-dimensional echocardiography is as reliable
      as the conductance catheter.

PMID- 9028122
TI  - [Rapid ventricular pacing in dogs--the natural history and pathology].
AB  - Six dogs were rapidly paced for 4 weeks with a VVI pacemaker, and observed for 4
      to 6 weeks after cessation of rapid pacing. Echocardiographic study revealed
      congestive heart failure at the end of rapid pacing associated with enlarged left
      ventricles and reduced left ventricular ejection fraction. Four weeks after
      cessation of rapid pacing, the left ventricular cavity and ejection fraction
      improved, but did not return to the normal pre-paced values. Six weeks after the
      cessation, cardiac function recovered, and pathological study of the resected
      hearts demonstrated normal myocardium without fibrotic or ischemic changes.

PMID- 9028123
TI  - [A case report of malignant schwannoma of the chest wall].
AB  - We described a very rare case of malignant schwannoma of the chest wall, which
      was surgically resected. The patient, a 40-year-old woman, came to our hospital
      because of an abnormal shadow in the right chest wall of an X-ray film without
      any symptoms. Computed tomography revealed a solid tumor attached to the
      posteroinferior aspect of the intrathoracic chest wall. The tumor was a 2.5 x 2.1
      cm, mass originating from the seventh intercostal nerve without pulmonary
      adhesion, and the patient underwent en bloc resection of the tumor. The
      pathological diagnosis was malignant schwannoma. The postoperative course was
      uneventful, and the patient, eight years after the operation is now doing well
      without local recurrence or distant metastasis. We reviewed seven cases of this
      type of tumor reported in the Japanese literature.

PMID- 9028124
TI  - [Retrieval of intravascular catheter fragment remaining for 15 years--a case
      report].
AB  - A 66-year-old woman was operated on aortic valve replacement, mitral valve
      replacement, and tricuspid annuloplasty. Retrieval of remaining Swan-Ganz
      Thermodilution catheter in the superior vena cava and the right atrium for 15
      years was also made. Fortunately, contamination and embolism have not occurred
      for 15 years. Extracted catheter showed to be stiff due to the degradation. It
      was suggested that the cause of remaining was the thread for closing the left
      atrium on the previous operation. The explanation to patient and one's
      recognition are most important. We recommend that retrieval of remaining catheter
      for a long time and/or after open heart surgery should be made under
      extracorporeal circulation because that remaining catheter may be involved with
      the intima, and preventing from bleeding.

PMID- 9028125
TI  - [A case report of aorto-coronary artery bypass surgery in patient with essential
      thrombocythemia].
AB  - Essential thrombocytosis was detected by chance in a 55-year-old patient with
      angina pectoris when cardiac catheterization was performed. The diagnosis of
      thrombocytosis (platelet count > 1,000000/mm3) was established by detailed
      investigations. This patient had stenosis of the coronary arteries and the right
      common iliac artery. About one month after cardiac catheterization, the patient
      underwent coronary bypass surgery following normalization of the platelet count
      with interferon therapy, which was also used to control the platelet count
      perioperatively. The operation was completed without major problems, and the
      postoperative course was uneventful. This case is reported in detail.

PMID- 9028126
TI  - [A case of successful operation of tetralogy of Fallot in a 55-year-old man].
AB  - A 65-year-old man with Tetralogy of Fallot having respiratory dysfunction is
      reported. He had a history of pulmonary tuberculosis and experienced right upper
      lobectomy and thoracoplasty, he had severe hypoxemia (PaO2 35.0 mmHg, Sat, 68.5%
      under room air) and low quality of life. Total corrective surgery (patch closure
      for ventricular septal defect, patch enlargement for right ventricular outflow
      tract, pulmonary valve replacement with bioprosthesis) was performed. Pulmonary
      edema which was similar to adult respiratory distress syndrome occurred on the
      first postoperative day after temporary weaning from respirator although
      circulatory correction was successful. Management with respirator was continued
      until the 7th postoperative day. It seemed that high pulmonary blood flow and
      pulmonary hypertension after operation resulted in increase of capillary
      permeability of lung. One month later there was no gait disturbance and no
      dyspnea (PaO2 59.8 mmHg, Sat. 92.3% under room air). This patient was the oldest
      one with Tetralogy of Fallot undergoing successful corrective surgery.

PMID- 9028127
TI  - [Two cases of coronary artery bypass grafting following radical mastectomy using
      bilateral internal thoracic arterial grafts].
AB  - We report two cases of coronary artery bypass grafting following radical
      mastectomy using bilateral internal thoracic arterial grafts. One was a 68-year
      old woman with angina pectoris, and the other was a 71-year-old woman with old
      myocardial infarction. Dissection of the internal thoracic arterial pedicles from
      the chest wall was not so difficult in both cases. The pedicles had good patency
      and each free flow of them was enough. They had no postoperative complications.
      It may be a useful method to use the internal thoracic arterial grafts for a case
      of coronary artery bypass grafting after radical mastectomy.

PMID- 9028128
TI  - [Successful surgical repair of composite graft detachment occurred 5 months after
      combined Bentall's operation and graft replacement with active aortitis
      syndrome].
AB  - Ninteen-year-old male with annuloaortic ectasia and resultant massive aortic
      valvular regurgitation, along with aortic aneurysmal dilatation extending from
      the root to the distal arch, underwent surgical repair at our hospital. Operative
      procedure comprised composite graft replacement of aortic valve-ascending aorta
      (Bentall's operation with Piehler's modification), combined with the aortic arch
      replacement with reconstruction of the neck vessels. Physical, laboratory, and
      histopathological findings revealed active aortitis syndrome as the etiology of
      this aortic disease. Five months after operation, this patient was readmitted
      because of his anemia and complaint of dyspnea. Two days after admission, his
      condition rapidly deteriorated into pulmonary edema with fall of blood pressure
      to 70 mmHg. Fluoroscopic examination taken after emergency intubation and
      mechanical ventilatory support showed malfunction of the aortic valve prosthesis.
      Circulatory assist was accomplished with intraaortic balloon counterpulsation and
      percutaneous cardiopulmonary bypass support, and emergent operation was carried
      out. On reentry into the anterior mediastinum, expansion of the aortic wall
      wrapping the graft was found. Incision into the wrapped aortic wall revealed
      dehiscence of the composite graft from the aortic annulus at the sites of right
      coronary cusp and noncoronary cusp position. Pooled blood between the graft and
      the wrapped aortic wall compressed the composite graft, resulting in tilting of
      the bi-leaflet mechanical valve prosthesis and restraint of the motion of one
      occluder. Retachment of the composite graft to the annulus from outside of the
      wrapped aortic root wall by seven felt-buttressed mattress sutures of 3-0
      polypropylene was performed. Postoperative course was smooth and successive
      strict antiinflammatory therapy with corticosteroid has successfully controlled
      the aortitis and the patient has been well after a follow-up of 18 months.

PMID- 9028129
TI  - [Successful repair of combined cardiac rupture and septal perforation after
      myocardial infarction].
AB  - A 78-year-old woman was operated on with a diagnosis of oozing-type cardiac
      rupture after an acute anteroseptal myocardial infarction. Pericardial drainage
      was performed and hemostasis was obtained by dressing with local hemostatics. As
      hemodynamics improved, elevation of pulmonary artery pressure and a step-up in
      oxygen concentration in the pulmonary artery from a Swan-Ganz catheter sample
      appeared. A left-to-right shunt was observed in the operative field with color
      Doppler echocardiography and a diagnosis of ventricular septal perforation (VSP)
      was made. Subsequently, intracavitary repair with two sheets of equine
      pericardial patch, sutured using interrupted mattress sutures with felt pledgets,
      was performed. Her early course after operation was satisfactory in spite of a
      small residual shunt. However, thirty-one days later she was returned to surgery
      because of an increasing residual shunt. Looseness of several interrupted
      mattress sutures and thrombus adherent to the internal surface of the pericardial
      patch were observed. The thrombus was removed and the patch was reattached using
      both interrupted mattress sutures with felt pledgets and continuous suture. She
      had an uneventful recovery thereafter. As double rupture is not a rare
      complication after myocardial infarction, a careful hemodynamic examination is
      necessary and important in the diagnosis and treatment of cardiac rupture. We
      consider that interrupted mattress sutures are a better technique for early
      repair of the VSP to reduce a risk of residual shunt due to the weakness and
      unclear border of infarcted myocardial tissue, and continuous suture is
      acceptable to repair the VSP 3 to 4 weeks later after infarction. Long-term
      anticoagulant therapy is necessary after intracavitary repair using equine
      pericardial patch.

PMID- 9028130
TI  - [A resected case of bronchogenic cyst of the left hemidiaphragm with elevated
      serum CA19-9].
AB  - A rare case of bronchogenic cyst of the left hemidiaphragm is reported. A 53-year
      old woman referred to our institution for an abnormal shadow on chest
      roentgenogram. Chest X-ray showed a 6 x 6 cm mass in the left lower lung filed.
      The margin of the mass was clear and the surface was smooth. The lateral view
      showed a mass on the diaphragm with the extrapleural sign. Chest CT demonstrated
      the mass as a multi loculated cyst. Celiac angiography demonstrated the branch of
      the inferior diaphragmatic artery at the margin of the mass. Her serum CA19-9
      level was 470 U/ml. The patient underwent surgical exploration. Operative
      findings showed the smooth surface mass was on the diaphragm covered with pleura.
      Resected tumor was large as 7.5 x 6.5 x 4.0 cm. The surface was smooth and white
      yellowish, and the cut surface presented a multi loculated cyts.
      Histopathological examination showed a bronchogenic cyst. CA19-9 in the cyst
      fluid was elevated as 445,900 U/ml. The serum CA19-9 level returned to normal
      after the operation.

PMID- 9028131
TI  - [A case of extracardiac noncoronary sinus Valsalva aneurysm associated with
      aortic regugitation].
AB  - A case of extracardiac noncoronary sinus Valsalva aneurysm was reported. A 11
      year-old male with history of mild AR was admitted to the hospital due to severe
      AR. Echocardiography revealed that the severe AR and an aneurysm in the posterior
      part of the ascending aorta. Angiography revealed that the origin of the aneurysm
      was noncoronary sinus. Operative findings showed that the aneurysm sized 23 mm by
      25 mm was an extracardiac type which grew posteroinferiorily at the left side of
      noncoronary sinus and that the dilation. Neither aortic valve nor the aortic
      route showed degenerative change. The ptosis of the valvular ring due to
      aneurysmal dilation of the noncoronary sinus caused AR. Then, valve repair
      composed by commissuroplasty and commissural suspension was carried out. And
      intraluminal patch closure technique in which the longitudinal diameter of patch
      was half of that of the aneurysm was effective on suspension of the valvular
      ring. Postoperative echocardiography showed decreasing of AR.

PMID- 9028132
TI  - [A case report of a fenestrated Fontan operation after bivalvation of the common
      atrioventricular valve in right isomerism].
AB  - The patient is a boy of five years old with asplenia, dextrocardia, right aortic
      arch, bilateral superior vena cavae, single atrium, common atrioventricular
      orifice, double outlet right ventricle and pulmonary stenosis. He underwent
      operations of right Blalock-Taussig shunt and right superior vena cava ligation
      when he was eight months old and at the age of three years old, bidirectional
      Glenn procedure and bivalvation of the common atrioventricular valve (CAVV) as
      he, then, suffered from severe regurgitation of the CAVV. The regurgitation
      improved from grade 3 to 1 and his recovery allowed the fenestrated Fontan
      operation at the age of four years and nine months. Bivalvation is an effective
      means for the mitigation of regurgitation of CAVV and paves the way for
      application of Fontan-type operation.

PMID- 9028133
TI  - [A surgical case report--rare association of tetralogy of Fallot with cor
      triatriatum, unroofed coronary sinus and persistent left superior vena cava].
AB  - We experienced the rare association of Tetralogy of Fallot with cor triatriatum,
      unroofed coronary sinus and persistent left superior vena cava. Only one case of
      this association has ever been reported in the literature. We successfully
      performed a total correction which consisted of a resection of the intra-left
      atrial fibrous membrane, reconstruction of the LSVC return pathway to the right
      atrium with PTFE graft, atrial partition with a bovine pericardial patch and the
      conotruncal repair for Tetralogy of Fallot. Cardiac catheterization 6 months
      after operation demonstrated the smooth drainage from LSVC into the right atrium
      without pressure gradient. His postoperative course has been uneventful.

PMID- 9028134
TI  - [Four cases of thymoma associated with pure red cell aplasia].
AB  - Thymomas associated with pure red cell aplasia (PRCA) constituted only 3.3% of
      122 thymomas treated in our department from 1963 to March, 1995. Four patients
      with this disease (2 men and 2 women, mean age: 58 years, range: 41 to 66 years
      old) are reported. Auto-antibodies were found in all 4 cases, increase of T cell
      in two, suppression of erythropoietin production in one, and antibody to EB virus
      in one. Operation was performed in all cases (two thymothymectomies, one extended
      thymothymectomy, and one thymomectomy), and 3 of 4 patients were in the
      progressive stage of Masaoka's classification (I, III, IVa, and IVb each). As for
      the pathological findings, mixed type was found in three cases and lymphocyte
      predominant type in one. Two patients died from radiation pneumonia. As for PRCA,
      postoperative therapy was effective (100%) in all patients.

PMID- 9028135
TI  - [Urgent replacement of aortic arch and descending aorta following replacement of
      ascending aorta for Stanford a aortic dissection--a case report].
AB  - A 37-year-old male who was on chronic dialysis regimen for IgA nephropathy
      developed acute Stanford A type aortic dissection. Replacement of the ascending
      aorta was performed with the aid of extracorporeal circulation, selective
      cerebral perfusion, and open distal anastomosis technique. The site of the
      intimal tear in the ascending aorta was resected and the gelatin-resorcin
      formaldehyde (GRF) glue was applied to both stumps. The outside of dissecting
      aortic wall was reinforced with Teflon-felt strips. Two months after the
      operation, the patient required an urgent operation due to threatening spindle
      evolution of a persisting dissection in the descending aorta. Replacement of the
      total arch and the descending aorta was carried out via the median sternotomy
      with the left anterior thoracotomy, and a subclavian incision. Continuous veno
      venous hemofiltration was initiated immediately after both operations and the
      water balance was maintained well. The patient was discharged 1 month
      postoperatively. It was suggested that the inside of the dissected aortic wall
      should be also reinforced even when the GRF glue was used in patients who have a
      fragile intimal flap and a wide tear.

PMID- 9028136
TI  - [Stage classification for pancreatic cancer: its difference between Japan and
      UICC].

PMID- 9028137
TI  - [Comparison of Gore-tex covered Ultraflex stent and bare Ultraflex stent:
      preliminary clinical results].
AB  - We clinically compared the covered Ultraflex stent and the bare Ultraflex stent
      for malignant esophageal strictures. Materials were 6 cases with esophageal
      carcinomas. We placed the Gore-tex covered stents (A group) in 4 cases including
      2 cases of esophagorespiratory fistulae, and the bare stents (B group) in 2
      cases. The stents were well-expanded in all cases. After stenting, dysphagia was
      improved in all cases. Fistulae were obstructed by the cover in 2 cases in A
      group. Mean survival term was 123 days in A group and 45 days in B group.
      Complications were fistulation of bare portion of the covered stent in one case
      in A group, and tumor bleeding in one case in B group. Considering of the risk of
      fistula or tumor bleeding, the cover is necessary to increase the safety and
      efficacy of the esophageal stent.

PMID- 9028138
TI  - [The mechanisms of the inhibition of gastric acid secretion induced by
      intraduodenal amino acids in rats].
AB  - We investigated the effect of intraduodenal amino acids (AA) on gastric acid
      secretion and gastrin release, and possible role of endogenous secretin on this
      phenomenon in vivo in rats. Intraduodenal administration of mixed AA solution
      (140 mg/hr, pH6.5) resulted in significant inhibition of gastric acid secretion
      and gastrin release stimulated by intragastric perfusion of peptone (0.5%).
      Intravenous infusion of secretin (0.05CU/kg/hr) also inhibited peptone-stimulated
      gastric acid secretion and gastrin release. Furthermore, the AA-induced
      suppression of gastric acid secretion was significantly blocked by intravenous
      injection of rabbit anti-secretin serum. In conclusion, intraduodenal AA inhibit
      peptone-stimulated gastric acid secretion and gastrin release, and endogenous
      secretin released by AA is attributed to this suppression. Thus, the result of
      this study indicates that intestinal AA regulate gastric secretory function
      mediated by AA-released endogenous secretin in the intestinal phase.

PMID- 9028139
TI  - [A case of gastric MALT lymphoma regressed endoscopically and pathologically
      after eradication of Helicobacter pylori].

PMID- 9028140
TI  - [A case of granular cell tumor of cecum].

PMID- 9028141
TI  - [A case of cecum cancer metastasizing to the spleen after right hemicolectomy].

PMID- 9028142
TI  - [A case of rectal varices treated with endoscopic injection sclerotherapy].

PMID- 9028143
TI  - [A case of nodular regenerative hyperplasia of liver with idiopathic
      hypereosinophilic syndrome].

PMID- 9028144
TI  - [A case of hepatic hemangiosarcoma in which heterogeneous MRI findings were
      useful for diagnosis].

PMID- 9028145
TI  - [A case of hepatocellular carcinoma detected by dynamic CT and MRI but not
      digital subtraction angiography].

PMID- 9028146
TI  - [A case of double choledochus with early gallbladder cancer].

PMID- 9028147
TI  - [Gallbladder metastasis from renal cell carcinoma--a report of a case].

PMID- 9028148
TI  - [Nine cases of malignant biliary stenosis treated with transpapillary placement
      of Wallstent].

PMID- 9028149
TI  - [Time course of disappearance of Helicobacter pylori after topical therapy and
      new triple therapy].

PMID- 9028150
TI  - Hepatic phenylalanine-hydroxylase and tyrosine-aminotransferase mRNA levels in
      rats adapted to diets with different concentrations of protein.
AB  - The effect of dietary protein concentrations on the hepatic expression of
      phenylalanine hydroxylase (PAH) and tyrosine aminotransferase (TAT) mRNA
      concentrations was studied in rats adapted to consume diets (18 or 50% casein) in
      a restricted schedule of 7 h (0900 to 1600) for 5 days. After 6 hours of feeding,
      TAT mRNA concentrations of rats adapted to 18% casein diet and fed acutely 6, 18
      and 50% casein diet were 0.15, 0.84 and 5.08 fold respectively higher than mRNA
      concentrations of rats before feeding. After 17 hours of fasting, TAT mRNA
      concentrations of rats previously fed 6, 18 or 50% casein diet were -0.45, 1.76
      and 9.11 fold respectively higher than mRNA concentrations of rats before they
      were fed. PAH mRNA concentrations showed a similar pattern. There was a -0.68,
      1.63 and 2.5 fold rise of PAH mRNA concentrations in rats fed 6,18 and 50% casein
      diet during the feeding period, and -0.86, 2.32 and 9.33 fold rise after 17 hours
      of fasting. TAT and PAH mRNA concentrations of rats adapted to consume 50% casein
      diet and then changed to 6% or kept on the 50% casein diet showed a maximum peak
      6 hours after the rats began to consume the diet; however, they decreased 5 hours
      after fasting. These results suggest that increasing concentrations of protein in
      the diet were able to increase the concentration of TAT and PAH mRNA, possibly in
      order to eliminate the excess of amino acids consumed. The concentration of TAT
      and PAH mRNA depended more on the protein content of the diet to which the rats
      were previously adapted.

PMID- 9028151
TI  - Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled
      diabetes.
AB  - OBJECTIVE: To examine the effects of vitamin E on total serum protein glycation
      (fructosamine), hemoglobin glycation (HbA1c), and serum levels of glucose, total
      cholesterol, triglycerides, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B.
      MATERIAL AND METHODS: Sixty poorly controlled diabetic patients were randomly
      assigned to receive either 1200 mg/day of vitamin E or identical placebo capsules
      during a two month period following a double blind cross-over design with a four
      week wash-out period between regimens. RESULTS: Seven patients were excluded from
      the study because of reasons not related to the medication. In the remaining 53
      patients, the levels of serum glucose, fructosamine, HbA1c, total cholesterol,
      HDL-C, LDL-C, Apo A1 and Apo B did not vary significantly with vitamin E as
      compared with placebo. CONCLUSIONS: No significant effects of vitamin E on any of
      the parameters evaluated were observed in poorly controlled diabetic patients.

PMID- 9028152
TI  - Case report of primary squamous carcinoma of the rectum.
AB  - PURPOSE: To report a patient with primary squamous carcinoma of the rectum. CASE
      REPORT: A 40-year-old woman with hematochezia and change in bowel habits was
      studied. The main laboratory finding was a mild anemia. A barium enema and a
      proctoscopy revealed a rectal neoplasm at eight cm from the anal verge. A
      transendoscopic biopsy demonstrated an squamous rectal carcinoma. A transrectal
      ultrasound and CT scan of the abdomen revealed a big rectal mass with transmural
      affection and possible involvement of the lymph nodes. The carcinoembriogenic
      antigen (CEA) was high (32 ng/mL). The patient underwent radiotherapy with 46 Gy,
      and 5-fluorouracil as radiosensitizer. Three months later, a new CT scan showed
      significant reduction of the size of the mass, and the patient underwent a very
      low anterior resection with double-stapled anastomosis. The analysis of the
      specimen showed a squamous carcinoma of the mid-rectum, invading through the wall
      without lymph node affection and with proximal, distal, and radial margins free
      of tumor. The CEA returned to normal after surgery (1.3 ng/mL). The patients is
      alive and without evidence of disease 18 months after the operation. CONCLUSION:
      Primary squamous carcinoma of the rectum is a rare disease, and surgery seems to
      be a good option of treatment, with the possibility of sphincter preservation
      depending upon the location of the tumor.

PMID- 9028153
TI  - Significance of lipid consumption during lactation.
AB  - Human milk lipids are the main source of energy to support optimum growth of the
      breast-fed infant. The content and composition of milk lipids come from three
      main sources of fatty acids: the diet, mobilization of body fat stores and fatty
      acid synthesis de novo by the mammary gland. On account of these, the consumption
      and composition of the lipids from the diet and also the nutritional state,
      specifically the body fat percentage of the lactating woman, are elements that
      maintain a close relation with the content and composition of milk lipids which
      translates into the energy content given to the baby. The evidence suggests that
      the body fat stores significantly provide the demand imposed by lactation, and
      under suboptimal nutritional conditions where body fat stores are depleted,
      dietary lipid consumption is essential. It is necessary to elucidate the
      physiological regulatory mechanisms involved in the utilization of dietary lipids
      on milk synthesis. This information will be of great practical value, since it
      may allow the development of optimum diets for lactating women.

PMID- 9028154
TI  - [Heterogeneity of ineffective erythropoiesis in myelodysplastic syndromes
      evaluated by application of newly devised parameters based on ferroerythrokinetic
      data].
AB  - Ineffective erythropoiesis was evaluated in 100 studies in 87 patients with
      myelodysplastic syndromes (MDS) applying newly devised parameters based on
      ferroerythrokinetic (FEK) data including erythron transferrin uptake (ETU). The
      efficiency ratio (R-Ef) was calibrated with V-2, the second canonical
      discriminant variate which underwent axis rotation. Based on discriminated FEK
      patterns, as previously reported, the patients were classified into five types
      i.e. I-z, ineffective, H-z, hemolytic hyperplastic, O-z, hypoplastic, I-H-z and I
      O-z, combination of these, groups. The proportion of I-z group was 48% and that
      of I-H-z and I-O-z groups was 30%. Significant correlations were obtained in I-z
      group between R-Ef and ETU (r = -0.628), unclear abnormality scores (R = 0.664)
      or ringed sideroblast scores (R = 0.742), scored by dummy variables regression.
      In the other groups, significant deviation from these correlations was observed,
      indicating that there is an obvious heterogeneity in MDS patients concerning
      association or dissociation of morphological abnormality, in addition to
      hyperplasia of erythroblasts, with or from ineffective erythropoiesis.

PMID- 9028155
TI  - [CDw90 (Thy-1) expression on CD34 positive cells in peripheral blood stem cell
      harvest].
AB  - In this study, we investigated CDw90 (Thy-1) expression in CD34+ cells and
      hematopoietic colony-forming ability in purified CD34+ Thy-1+ and CD34+ Thy-1
      fractions in the peripheral blood at the PBSCH. The high proliferative potential
      colony-forming cells (HPP-CFC), which are considered to be more primitive
      hematopoietic stem cells, were found more frequently in the purified CD34+ Thy-1+
      fraction than in the purified CD34+ Thy-1- fraction. Thus, it is useful to decide
      the optimal time of PBSCH to measure the CD34+ Thy-1+ cells as well as CD34+
      cells in the peripheral blood by flow-cytometry. In CD34+ acute myeloblastic
      leukemia (AML) cells, the co-expression rate of CD34 and Thy-1 was negative,
      suggesting that it may be possible to estimate the contamination of CD34+ AML
      cells by the Thy-1 expression rate in CD34+ cells at PBSCH.

PMID- 9028156
TI  - [Rapid onset of hemolytic anemia after allogeneic bone marrow transplantation
      from an unrelated ABO major mismatched donor].
AB  - A 46-year-old woman with chronic myelogenous leukemia received allogeneic bone
      marrow transplantation from an unrelated human leukocyte antigen (HLA) matched
      (but mixed lymphocyte culture (MLC) positive to graft-versus host disease (GvHD)
      donor. The blood type of the recipient was A type Rh (+) while the donor blood
      type was B type Rh (+). The patient received busulfan 8 mg/kg, cyclophosphamide
      120 mg/kg, and total-body irradiation 10 Gy before bone marrow transplantation.
      Short-term administration of methotrexate and cyclosporin was given for
      prophylaxis of GvHD. The mononuclear cells harvested from the donor were
      concentrated by COBE Spectra before bone marrow transplantation. Although
      engraftment of transplanted bone marrow in the recipient was confirmed on day 11,
      the patient suffered from severe anemia on day 10. Since the direct Coombs' test
      to A type red blood cells was positive, and anti-A antibody titer increased 16
      fold, we diagnosed her anemia as hemolytic anemia caused by ABO mismatched
      transplantation. In addition to hemolytic anemia, she had skin symptoms of acute
      GvHD grade II, microangiopathic hemolytic anemia, and died of multiple organ
      failure on day 44. This experience indicated that some allogeneic transplant
      recipients are at risk of severe hemolytic anemia in the early stage after
      unrelated ABO mismatched donor and that it is necessary to establish proper
      treatment and prophylaxis.

PMID- 9028157
TI  - [Smoldering leukemia with CD7.CD34(+), immunoglobulin heavy chain rearrangement
      (+) and hypoplastic marrow with myelofibrosis].
AB  - A 63-year-old male was admitted because of pneumonia. Peripheral blood findings
      showed pancytopenia with increase of blasts. A bone marrow specimen showed
      hypocellular marrow with increase of blasts. The blasts were positive for CD7,
      CD34, and HLA-DR and negative for other lymphoid antigens and myeloid antigens
      involving myeloperoxidase. Rearrangement of immunoglobulin heavy chain was
      demonstrated by Southern blotting analysis. T cell receptor beta, T cell receptor
      gamma and immunoglobulin light chain rearrangement were negative. A diagnosis of
      stem cell leukemia was made. In vitro, the blasts did not respond to recombinant
      human granulocyte colony-stimulating factor (rhG-CSF), cytarabine (Ara-C) and all
      trans retinoic acid (ATRA). However, in the blasts of culture without cytokeins,
      CD33 expression was newly induced. Remission was not obtained by chemotherapies
      with cyclophosphamide, etoposide, prednisolone and Ara-C. Four months later,
      marrow specimens showed hypoplasty with myelofibrosis. One year later, the blasts
      showed CD33 expression with negative myeloperoxidase. The leukemia was
      transformed to minimally differentiated myeloid leukemia from stem cell leukemia.
      This condition was thought to be "smoldering leukemia" because of the slow
      development and refractoriness to chemotherapy. Nineteen months later the patient
      died due to respiratory failure by pneumonia and pulmonary bleeding despite
      therapy.

PMID- 9028158
TI  - [Werner's syndrome developing acute megakaryoblastic leukemia with der(1;7)].
AB  - A 46-year-old man with Werner's syndrome was admitted with epigastralgia and body
      weight loss. The peripheral blood findings showed anemia, thrombocytosis and
      eosinophilia. Bone marrow aspiration and biopsy revealed increases in eosinophils
      and megakaryocytes, myelodysplastic change with 6.6% myeloblast, and
      myelofibrosis. Chromosomal analysis revealed 46, XY, +der(1;7), -7, del(20). He
      was diagnosed as having myelodysplastic syndrome with myelofibrosis or essential
      thrombocythemia. Three months later, pancytopenia appeared with a relative
      increase of blasts positive for CD41 and negative for myeloperoxidase. He died of
      respiratory failure due to pneumonia. An autopsy revealed severe myelofibrosis
      with proliferation of megakaryocytes and blasts. A final diagnosis of acute
      megakaryoblastic leukemia was made. Werner's syndrome is rare, and it is even
      more unusual to have the complication of acute leukemia with der (1;7) seen in
      this case.

PMID- 9028159
TI  - [The detection of minimal residual disease by DEK/CAN chimeric m-RNA in a case of
      AML M2 with translocation t(6;9) (p23;q34) after chemotherapy and peripheral
      blood stem cell transplantation].
AB  - A 18-year old female with acute myelogenous leukemia (AML), M2 had translocation:
      t(6;9) (p23; q34). The patient entered into hematological complete remission
      after two courses of BHAC-DMP chemotherapy with disappearance of cytogenetic
      abnormality. However, minimal residual disease (MRD) detected with DEK/CAN
      chimeric m-RNA by reverse transcription polymerase chain reaction (RT-PCR) was
      continuously observed, although decreased quantitatively, following several
      courses of consolidation and intensification chemotherapies. MRD was detected
      also in the harvested peripheral blood stem cells (PBSC). Leukemia relapsed with
      the reappearance of t(6;9) 2 months after the subsequent peripheral blood stem
      cell transplantation (PBSCT). Leukemia became refractory to chemotherapy, and the
      patient died 5 months thereafter.

PMID- 9028161
TI  - [Intracranial hypertension in a patient with acute promyelocytic leukemia treated
      with all-trans retinoic acid].
AB  - A 21-year-old Japanese woman was referred to our hospital because of severe
      anemia and thrombocytopenia. Bone marrow aspiration showed a hypercellular marrow
      with 91.5% promyelocytes. Cytochemical study and surface marker a diagnosis of
      acute promyelocytic leukemia. Because leukocyte count elevated, she was treated
      with all-trans retinoic acid (ATRA) after conventional chemotherapy. After 11
      days of ATRA therapy, the patient started to develop severe headache, nausea and
      diplopia. Ophthalmologic examination revealed bilateral papilledema. Computed
      tomography and magnetic resonance imaging of the head showed no intracranial
      lesion. ATRA was discontinued because it was suspected to cause intracranial
      hypertension. Her symptoms were relieved and patilledema improved gradually. ATRA
      is safe and well-tolerated, if the retinoic acid syndrome can be prevented or
      managed. As the tolerable dose of ATRA in adults is higher than that in children,
      the side effects tend to occur in children. In Japan, only two childhood cases of
      intracranial hypertension during ATRA therapy have been reported. We must
      remember the possibility of intracranial hypertension during ATRA therapy, even
      in adults.

PMID- 9028160
TI  - [Early establishment of bone marrow hypoplasia by antileukemic chemotherapy with
      concurrent rhG-CSF in a case of acute myelogenous leukemia complicated with
      intestinal perforation].
AB  - We report a case of 53-year-old man with acute myelogenous leukemia (M2) showing
      a karyotype of t(7;11) (p15;p15), del(10) (q11;q12), who was complicated with
      perforation of a duodenal ulcer during the antileukemic chemotherapy using
      behenoyl ara-C, daunorubicin, 6-mercaptopurine and prednisolone. As his bone
      marrow still showed high cell density and leukemic proliferation at the time of
      intestinal perforation, the therapeutic regimen was changed to a combination of
      behenoyl are-C and mitoxantrone, and daily rhG-CSF was concurrently administered
      for the purpose of early establishment of bone marrow hypoplasia. On the 8th day
      after the therapeutic regimen had been changed, his bone marrow became nearly
      aplastic, and complete remission was obtained on the 24th day. This case may
      indicate that the concurrent administration of cell-cycle specific antileukemic
      drugs and rhG-CSF is available for AML patients with emergent need of leukemic
      cell reduction.

PMID- 9028162
TI  - [False positive FDP test associated with malignant lymphoma].
AB  - We present a man with non-Hodgkin's lymphoma who had false positive FDP test
      results and who had monoclonal IgM and IgG. At admission, laboratory examinations
      showed elevated FDP levels and prolonged PT and APTT, which did not improve by
      anti-coagulation therapy. Although coagulation system data returned to normal
      levels after steroid pulse therapy, the FDP level increased. Positive pregnancy
      test and results of dilution analyses on FDP assay yielded a diagnosis of false
      positive FDP test results due to serum latex agglutinin. The addition of anti
      immunoglobulin antibody inhibited latex agglutination by serum. FDP levels
      positively correlated with serum IgM concentrations. These data suggest that the
      false positive FDP test in this case was due to latex agglutination by monoclonal
      IgM.

PMID- 9028163
TI  - [Plasma cell leukemia with amyloid deposition and osteogenetic change at the site
      of an extramedullary plasmacytoma].
AB  - A 49-year-old man was admitted with swelling in the left lower extremity, and a
      mass in the left lower abdomen. Laboratory findings showed an increased WBC of
      15,000/microliter with 41% plasma cells, and immunoglobulin (Ig) A of 2,557mg/dl
      with a monoclonal component. A roentgenogram and computed tomograph of the
      abdomen revealed that a 5 x 10 cm mass with calcification located in the
      iliopsoas muscle. Plasma cell leukemia with extramedullary plasmacytoma was
      diagnosed, and the patient was treated with high-dose dexamethasone (40 mg/day
      for 4 days), resulting in a good response with the disappearance of plasma cells
      in peripheral blood and a marked decrease in serum Ig A. However, the patient's
      condition deteriorated in spite of various treatments, and he died of heart
      failure 5 months after admission. With informed consent from relatives, a
      necropsy was performed and infiltration of plasma cells in the mass in the
      iliopsoas muscle was noted. We reported this case because plasma cell leukemia
      with amyloid deposition and osteogenesis at the site of extramedullary
      plasmacytoma is very rare.

PMID- 9028164
TI  - [Allopurinol induced pancytopenia in a patient with myeloproliferative disorder].
AB  - We reported a rare case of pancytopenia caused by allopurinol. A 61-year-old man
      was first admitted in May 1993, because of thrombocytosis. He had suffered from
      chronic glomerulonephritis. He was administered allopurinol for hyperuricemia
      from March 1993. On first admission the laboratory findings revealed leukocytosis
      (10,100/microliter) and thrombocytosis (971 x 10(3)/microliter) in the peripheral
      blood. Myelofibrosis was strongly suspected due to increased number of MgK and
      reticular fiber in the bone marrow. Two months later, he readmitted due to
      pancytopenia (WBC 1,300/microliter, Hb 6.2g/dl, Plt 10 x 10(3)/microliter). His
      bone marrow showed markedly hypocellular. Because we suspected that pancytopenia
      was induced by allopurinol, we discontinued allopurinol and administered
      oxymetholone, G-CSF, and EPO, WBC, RBC, and platelet count had been recovered
      about one and half months later. In vitro co-culture indicated that CFU-G, E, and
      Meg in the bone marrow cells after recovery from pancytopenia were markedly
      suppressed in the presence of patient's serum and oxipurinol. Pancytopenia due to
      allopurinol was reported to be rare, and some authors showed that it will
      sometimes be fatal. Because pancytopenia of this case had been recovered in a
      relatively short time with cytokine therapy, it was thought to be effective for
      pancytopenia due to drug like this case.

PMID- 9028165
TI  - [Chronic myelogenous leukemia expressing two bcr-abl chimeric mRNA; a case
      report].
AB  - Chronic myelogenous leukemia (CML) expresses two types of bcr-abl chimeric mRNA.
      One is b3a2 type in which bcr exon 3 binds to abl exon 2, the other is b2a2 type
      that bcr exon 2 binds to abl exon 2. Either bcr-abl is normally expressed, but
      both types of bcr-abl mRNA can be expressed at the same time in a patient. We
      report here a rare case of CML expressing two types of bcr-abl mRNA and discuss
      the possibility that this double expression would help to monitor the clinical
      course of CML.

PMID- 9028166
TI  - [How does, bacteriorhodopsin convert light into energy?].

PMID- 9028167
TI  - [Photochemical reaction centers].

PMID- 9028168
TI  - [Phytochrome: a plant sensor for environmental light conditions].

PMID- 9028169
TI  - [Structure and photochemical reactions of photoactive yellow protein].

PMID- 9028171
TI  - [Ecology of influenza viruses: are we prepared for the emergence of the next
      pandemic of influenza].

PMID- 9028170
TI  - [Photoreactive nitrite hydratase].

PMID- 9028172
TI  - [NADH-quinone oxidoreductase: the hugest and most complicated membrane-bound
      enzyme complex].

PMID- 9028173
TI  - [What we can learn from the whole genome sequence of an archaeon Methanococcus
      jannaschii].

PMID- 9028174
TI  - [Biomolecular electronic device using an artificial flavocytochrome].

PMID- 9028175
TI  - Alveolar breath sampling and analysis to assess exposures to methyl tertiary
      butyl ether (MTBE) during motor vehicle refueling.
AB  - Methyl tertiary butyl ether (MTBE) is added to gasoline (15% by volume) in many
      areas of the U.S. to help control carbon monoxide emissions from motor vehicles.
      In this study we present a sampling and analytical methodology that can be used
      to assess consumers' exposures to MTBE that may result from routine vehicle
      refueling operations. The method is based on the collection of alveolar breath
      samples using evacuated one-liter stainless steel canisters and analysis using a
      gas chromatograph-mass spectrometer equipped with a patented "valveless"
      cryogenic preconcentrator. To demonstrate the utility of this approach, a series
      of breath samples was collected from two individuals (the person pumping the fuel
      and a nearby observer) immediately before and for 64 min after a vehicle was
      refueled with premium grade gasoline. Results demonstrate low levels of MTBE in
      both subjects' breaths before refueling, and levels that increased by a factor of
      35 to 100 after the exposure. Breath elimination models fitted to the post
      exposure measurements indicate that the half-life of MTBE in the first
      physiological compartment was between 1.3 and 2.9 min. Analysis of the resulting
      models suggests that breath elimination of MTBE during the 64 min monitoring
      period was approximately 115 micrograms for the refueling subject while it was
      only 30 micrograms for the nearby observer. This analysis also shows that the
      post exposure breath elimination of other gasoline constituents was consistent
      with previously published observations. These results demonstrate that this new
      methodology can be used effectively in studies designed to assess exposures to
      MTBE. The method can be used to objectively demonstrate recent exposures, the
      relative magnitude of an exposure, and the approximate duration of the resulting
      bloodborne dose. Once a blood/breath partition coefficient for MTBE has been
      firmly established, the bloodborne concentration of the absorbed material can be
      determined using these techniques as well.

PMID- 9028176
TI  - Aerobic treatment of a nitrogen-limited chemical process wastewater.
AB  - Nitrogen transformations and their effect on aerobic suspended growth treatment
      of an industrial wastewater were studied in three parallel bench-scale reactors
      operated at 5 degrees C at mean cell residence times (MCRT) of 15, 30, and 60
      days. In normal process wastewater, the bulk of influent nitrogen was in organic
      form, and the fraction transformed was almost totally incorporated into
      synthesized biomass. Assimilative control by heterotrophs maintained ammonia
      nitrogen levels below permitted effluent levels, and nitrification was not
      significant. Although volatile suspended solids had a nitrogen content of only 5%
      to 8%, effective organics removal was maintained, and total organic carbon and
      filtered daily average five-day biochemical oxygen demand (BOD5) were below
      permitted effluent levels. A marked improvement in settleability and lower
      effluent total suspended solids was achieved by adding ammonia-nitrogen to the
      wastewater in excess of stoichiometric growth requirements. During a batch
      production cycle of a cationic chemical, the ratio of nitrogen to chemical oxygen
      demand and the fraction of the total influent nitrogen in soluble form increased
      in the wastewater. Reactor effluent ammonia levels increased to above permit
      levels at all three MCRTs during treatment of wastewater containing cationic
      production effluents. The magnitude of ammonia increase was greater for longer
      MCRTs, suggesting that synthesis of cell mass was not capable of assimilating the
      increased ammonia supply under these non-steady conditions. The experimental
      results suggest several potential strategies for operating the aerobic process at
      the treatment facility, including adding nitrogen to improve settleability and
      discontinuing these additions when wastewater contains a high ratio of nitrogen
      to chemical oxygen demand and an elevated soluble nitrogen fraction.

PMID- 9028177
TI  - A socioeconomic assessment of human exposure to ozone in the South Coast Air
      Basin of California.
AB  - The purpose of this study is to assess by age, race, ethnicity, and income the
      effects of air pollution control measures and population growth on human exposure
      to ozone in the South Coast Air Basin of California (SoCAB). A methodology to
      study human exposure to air pollutants from a socioeconomic perspective has been
      developed. Specifically, the Regional Human Exposure model (REHEX-II) has been
      applied to estimate historical (1980-1982) and recent (1990-1992) human exposure
      to ozone. The model accounts for time spent in different microenvironments for
      different age groups and incorporates long-term air quality data with high
      spatial resolution. The simulation results, expressed as per capita hours of
      exposure to ozone above various concentration thresholds, are associated with
      population race, ethnicity, and per capita income. The results indicate that
      ozone exposure differences by race and ethnicity have diminished over time.
      However, the study suggests that on average, low income areas may be experiencing
      higher ozone exposure than high income areas, suggesting that environmental
      health risks (e.g., respiratory diseases) may be systematically higher for low
      income groups in the SoCAB.

PMID- 9028178
TI  - John Hunter: his origins and his influence.

PMID- 9028179
TI  - Dentistry and the new National Health Service of 1948.

PMID- 9028180
TI  - Root end filling materials: a review.
AB  - When non-surgical attempts prove unsuccessful or are contraindicated, surgical
      endodontic therapy is needed to save the tooth. The procedure usually consists of
      exposure of the involved area, root end resection, root end preparation and
      insertion of a root end filling material. Numerous materials have been suggested
      as root end filling materials. This article is a review of the literature on the
      suitability of various root end filling materials based on their leakage
      assessment, marginal adaptation, cytotoxicity, and usage test in experimental
      animals and humans.

PMID- 9028181
TI  - Assessment of antibacterial activity of endodontic sealers by a direct contact
      test.
AB  - It is recognized that endodontic success depends on bacterial elimination from
      the root and root canal system. Antibacterial activity of endodontic sealers can
      improve the success rate of endodontic treatment, provided the physical
      properties are not compromised. The aim of this study was to evaluate the
      antimicrobial properties of two endodontic sealers (AH26 and Endoflas) using a
      direct contact test (DCT) which was designed for this purpose. The DCT is based
      on measuring the effect of close contact between test bacteria and the tested
      material on the kinetics of bacterial outgrowth using a temperature controlled
      microplate spectrophotometer (THERMOmax). For comparison, the agar diffusion test
      (ADT) was performed for both materials. The results of the DCT showed that
      Endoflas was a significantly more potent bacterial growth inhibitor than AH26,
      whereas when assessed with the ADT, AH26 was capable of producing a larger
      inhibition zone than Endoflas. The DCT, by being quantitative and virtually
      independent of solubility and diffusion, was found more suitable to assay solid
      surfaces. The results demonstrated the added value of DCT in the study of the
      antimicrobial properties of endodontic sealers.

PMID- 9028182
TI  - Reasons for apicectomies. A retrospective study.
AB  - A retrospective study was carried out to evaluate the clinical factors involved
      in deciding to perform apicectomies. Five hundred and seventeen teeth from 392
      patients (211 women and 181 men) that had undergone apicectomy during the period
      from September, 1990 to December, 1992 were assessed using the patients' clinical
      records. The information recorded included the source of referral, the quality of
      preoperative root canal filling, the size of periradicular lesion, the type of
      the lesion (for biopsed lesions), the type of coronal and radicular restorations,
      and the different factors that influenced the decision to perform an apicectomy
      for each tooth. These factors were classified into technical and biological, and
      when they occurred together they were classified as combined. The decisions to
      perform apicectomies most commonly involved combined technical and biological
      factors. Biological factors alone only amounted to 35% of the total. Technical
      factors alone amounted to only 3% of the total. When all factors were considered,
      biological factors constituted 60%, whilst technical factors constituted 40%, of
      the total. The most common biological factors were persistent symptoms (54%), and
      continuing presence of a periradicular lesion (44%). The most common technical
      factors were post crown (60%) and crowned teeth without posts (31%). This study
      emphasised the need for a high standard of conventional root canal treatment in
      order to avoid surgical treatment.

PMID- 9028183
TI  - Pulp exposure after stepwise versus direct complete excavation of deep carious
      lesions in young posterior permanent teeth.
AB  - The aim was to assess the prevalence of pulp exposure after stepwise versus
      direct complete excavation of permanent posterior teeth with deep carious
      lesions. The material, representing 116 patients aged 6-16 yrs (mean = 10.2 yrs),
      consisted of 127 teeth with radiographs revealing carious lesions to such a depth
      that pulp exposure could be expected if direct complete excavation was performed.
      Teeth with clinical symptoms, other than transient pain shortly before treatment,
      were not accepted. The teeth were randomly selected for either treatment
      procedure. Stepwise excavation implied removal of the bulk of carious tissue and
      application of calcium hydroxide, followed by sealing of the cavity with zinc
      oxide eugenol cement. After a period of 8-24 weeks the rest of the carious dentin
      was removed and the cavity sealed with calcium hydroxide, zinc-oxide-eugenol
      (ZOE) and a restorative material. Direct complete excavation entailed removal of
      all carious dentin followed by sealing as mentioned above. In case of pulp
      exposure, pulp treatment was performed. The pulp was exposed in 40 of the teeth
      treated by direct complete excavation. The corresponding figure for those treated
      by stepwise excavation was 17.5%. The difference was statistically significant.
      The teeth with no pulp exposure after direct or stepwise excavation showed normal
      clinical and radiographic conditions at the last check-up (mean = 43 months).

PMID- 9028184
TI  - Factors affecting the wear of sonic files.
AB  - The aim of this study was to investigate factors affecting the wear and cutting
      ability of sonic files. A model system was used and the following variables
      evaluated, file type; Heliosonic, Rispisonic or Shaper, load; 25, 50 or 100 grams
      and length of time in use; new, 30 or 60 seconds. A 3(3) full factorial analysis
      with two replications into the effect of the above variables on the cutting
      ability of the Heliosonic, Rispisonic and Shaper files powered by the MM1500
      sonic instrument was performed. A new file size 25 (Heliosonic and Shaper) or No
      3 (Rispisonic) was used for each cut together with water irrigation and the
      substrate used was 1 mm thick sections of bovine bone. All variables had a
      significant effect on cutting (ANOVA. p < 0.001). However examination of the F
      values showed that the most significant variable was load, followed by file type,
      and time. The most significant interaction was between file type and load
      followed by time and file type. The interaction between time and load was not
      significant (p > 0.05). The Rispisonic file was most susceptible to wear during
      use especially at higher loads and the Heliosonic file cut least. It is suggested
      that the Shaper file is the better design of the three with respect to cutting
      ability and wear with use.

PMID- 9028185
TI  - 3-hydroxy fatty acids in a lipopolysaccharide-like material from Treponema
      denticola strain FM.
AB  - Treponemes are associated with major oral diseases such as apical and marginal
      periodontitis. Lipopolysaccharide (LPS) is regarded as an important virulence
      factor in these diseases. It is unclear whether LPS is present in oral
      treponemes. Therefore, the present study was undertaken to examine if a common
      oral treponeme-Treponema denticola-possesses LPS. A modified Westphal method
      (phenol water-ethanol-hexane extraction) was used to extract LPS-like material
      from T. denticola, reference strain FM. It was cultivated in prereduced
      anaerobically sterilized pectin medium. Gas chromatography and gas chromatography
      mass spectrometry of the extract detected three hydroxy fatty acids: C3-OH-i
      13:0, C3-OH-i-15:0, and C3-OH-16:0 which constituted 12% of its fatty acid
      content. These acids, commonly regarded as markers of LPS, suggested the presence
      of LPS in T. denticola.

PMID- 9028186
TI  - Conservative treatment of dens evaginatus of anterior teeth.
AB  - Dens evaginatus is a developmental malformation characterized by the presence of
      an extra cusp. In the anterior dentition, dens evaginatus is more commonly found
      in the maxilla and on the palatal surface of the tooth. Treatment may include
      root canal therapy followed by either an aesthetic restoration or a full crown
      coverage. In cases of mesiodens, supernumerary teeth or crowded dentition,
      extraction is often indicated. Presented is a case of a conservative treatment
      modality of dens evaginatus in a mandibular central incisor.

PMID- 9028188
TI  - Measurement of tooth mobility in children using the periotest.
AB  - This study investigated the use of the periotest for measuring tooth mobility of
      upper permanent incisor teeth in children. A total of 160 children, with equal
      numbers of boys and girls aged between 9 and 16 years had two periotest readings
      made on their four upper incisor teeth. In all 1,280 measurements were collected
      and analysed. The results showed that the second periotest readings were
      statistically significantly higher than the first. Periotest readings were lower
      for girls than boys of the same ages. The periotest may have a place as a
      diagnostic tool in paediatric dentistry and dental traumatology, however, further
      research is necessary before the periotest can be used to assist in the diagnosis
      and assessment of healing of traumatised teeth.

PMID- 9028187
TI  - Management of intrusive luxation injuries.
AB  - Traumatic intrusion of permanent teeth is a relatively infrequent but serious
      type of dental injury, due to the complicated picture it involves. Various
      treatment approaches have been suggested, so far, regarding management of
      intrusive luxation. Techniques aiming to reposition the intruded tooth include
      observation for spontaneous reeruption, surgical as well as orthodontic
      repositioning. However, development of complications such as pulp necrosis,
      inflammatory root resorption, replacement resorption and ankylosis and loss of
      marginal bone support makes selection of the most favorable technique
      controversial. In this paper, a critical review of the existing treatment
      modalities is attempted and treatment approaches based on diagnostic parameters
      that are indicative of the severity of an intrusive injury are presented.
      Recommendations are made after taking into consideration experimental and
      clinical study findings and observations from other author's and our own clinical
      experience. Two cases of intrusive luxation in children are presented and
      management of the dental injuries as well as the complications which occurred are
      being discussed.

PMID- 9028189
TI  - Impact resistance of crowned endodontically treated central incisors with
      internal composite cores.
AB  - The impact fracture resistance of crowned endodontically treated teeth with
      composite cores but without posts, that had either no coronal dentin remaining or
      a 1 mm dentin collar was compared to that of unrestored caries free teeth. The
      teeth were struck mid-labially to simulate a common trauma situation using a
      pendulum device and fracture resistance determined by calculation of absorbed
      energies. No significant difference was found between the intact teeth and the
      crowned root treated teeth with composite core and a 1 mm dentin collar. Crowned
      root treated teeth with a composite core but no coronal dentin had significantly
      reduced fracture resistance (p < 0.05). Teeth with the dentin collar mainly
      fractured obliquely from the buccal crown margin to a point coincident with the
      simulated alveolus, representing a clinical situation which would allow retention
      rather than extraction of the tooth.

PMID- 9028190
TI  - Prognosis of root-fractured permanent incisors.
AB  - The prognosis of 56 root-fractured permanent incisors was evaluated clinically
      and radiographically for 2 to 31 years. Information about initial case histories,
      examination and treatment of root-fractured teeth were recorded retrospectively
      from patient cards. Most of the root fractures occurred in the 16-20 year age
      group (38%) followed by the 11-15 year age group (29%). Males were involved more
      often than females. Fifty-two percent of the patients visited the dental clinic
      within the first week, while 48% did so 1 month-31 years later after the injury.
      The leading cause of root fractured injuries was falls (46%) and mostly involved
      one tooth (71%). Maxillary central incisors were the most often affected teeth
      (95%). The most common type of root fracture was in the middle third of the root
      (57%) followed by apical part (34%). About 59% of untreated or splinted teeth
      maintained their vitality. Healing with connective tissue was observed in 19
      teeth, with calcified tissue in 15 teeth and with osseous tissue in only one
      tooth. There was partial or complete obliteration of the pulp space in these
      healed cases (62.5%). The formation of pulpal hard tissue produced no additional
      clinical problems. Partial or total pulp necrosis were noted in 21 (37.5%) teeth.
      Endodontic treatment was successful in 12 cases. The remaining 9 teeth were
      extracted due to the loss of marginal alveolar bone and apical periodontitis.

PMID- 9028191
TI  - Management of dens evaginatus: evaluation of two prophylactic treatment methods.
AB  - Dens evaginatus (DE) is an odontogenic anomaly characterized by an enamel covered
      tubercle, enclosing dentin and pulpal tissue. It most commonly affects premolar
      teeth of people of mongoloid ethnicity. The prevalence of DE in Singapore is
      2.1%. Fracture or attrition of the tubercle may lead to pulpal necrosis. Thus,
      prophylactic management of DE is preferred. A retrospective cohort study
      comparing two common prophylactic restorative methods was conducted. This
      involved 817 children, aged 10 years at the outset, having 1591 DE. The teeth
      were observed for 2 years. The results showed that significantly less teeth
      developed pulpal pathology when an enamoplasty-preventive resin restoration
      method was used (0.52%) as compared to an amalgam cavity restoration (5.37%) and
      the control (3.65%) [chi 2 = 9.595 (p < 0.01) df = 2]. Knowledge of the various
      treatment options and prevalence data is important as there is an increasing
      global migration of people of mongoloid ethnicity.

PMID- 9028192
TI  - Torsional and bending properties of stainless steel and nickel titanium Canal
      Master U and Flexogate instruments.
AB  - The purpose of this study was to assess and to compare the torsional and bending
      properties of the Canal Master U (CMU) and Flexogate instruments made of
      stainless steel and nickel titanium. The bending moment, the torsional moment and
      angular deflection were measured according to ANSI/ADA specification number 28
      and ISO reference number 3630. Ten instruments of each size, sizes 25 to 40 were
      used for each test. Nickel titanium instruments were significantly more flexible
      than stainless steel files. With regard to the torsional moment, values obtained
      were below the standards in all sizes except stainless steel CMU sizes 25, 35 and
      40, and nickel titanium CMU size 25. Nickel titanium instrument also showed the
      highest angular deflection values. There were statistically significant
      differences between nickel titanium files and stainless steel Flexogates and
      between stainless steel Flexogates and stainless steel CMU. Based on these
      findings, the use of nickel titanium CMU and Flexogates is encouraged. Given the
      perceived advantages of both CMU and Flexogate instruments over conventional
      files for canal preparation, it would appear desirable to have the torque
      resistance of these instruments improved.

PMID- 9028193
TI  - Role of cementoenamel junction on the radicular penetration of 30% hydrogen
      peroxide during intracoronal bleaching in vitro.
AB  - Intracoronal bleaching of nonvital, teeth with 30% hydrogen peroxide is
      occasionally associated with external cervical root resorption. The exact
      mechanism by which bleaching induced root resorption occurs is not yet fully
      understood. The relationship of cementum to the enamel at the cementoenamel
      junction may have clinical significance. Seventeen single rooted human mandibular
      premolars extracted atraumatically for orthodontic reasons were used. The
      radicular hydrogen peroxide penetration in each tooth was measured in vitro by an
      indirect colorimetric method. Thereafter, the teeth were examined with a scanning
      electron microscope to determine the type of the cementoenamel junction. It was
      found that the radicular penetration of 30% hydrogen peroxide was related to the
      type of cementoenamel junction.

PMID- 9028194
TI  - Periapical actinomycosis: report of a case and review of the literature.
AB  - This case of periapical actinomycosis presented the clinical picture of chronic
      periapical inflammation. The diagnosis was based on the histological examination
      of the periapical lesions suggesting the necessity for routine histological
      examination. Although root canals provide a primary port of entry the Actinomyces
      organisms into the periapical tissue, periapical actinomycosis, is considered
      extremely rare. This may be due to the omission of routine histological
      examination of periapical lesions and the clinical behavior of the disease. The
      large number of cases reported during the last decade indicates that periapical
      actinomycosis is more frequent than what it is believed and this is important in
      the daily dental practice.

PMID- 9028195
TI  - Polylactic acid (PLA) root replica in ridge maintenance after loss of a
      vertically fractured incisor.
AB  - A periodontally affected tooth was prepared for a special treatment: Calcium
      hydroxide was introduced into the apical half of the root canal whereas its
      cervical part was filled with glass ionomer cement. The tooth was shortened
      subgingivally. After 6 weeks of epithelization over the residual root a palatal
      full-thickness flap was mobilized. The root was carefully extracted and chairside
      copy-milled from the biodegradable polylactic acid (PLA) material. The PLA
      replica was implanted immediately into the socket and the flap was sutured. Aim
      of the treatment was to prevent the ridge collapse of the extraction area. Ridge
      height could be preserved during the 21 months of observation. With time the
      radiographic density of the cancellous bone increased in the implanted area,
      indicating that a PLA-replica is replaced by host's bone tissue.

PMID- 9028196
TI  - Young's modulus of warm and cold gutta-percha.
AB  - The purpose of this study was to evaluate the Young's modulus of cold and warm
      gutta-percha. Rods of gutta-percha. Specially designed by three companies were
      tested at 20 degrees C and 55 degrees C with a tensile testing machine. The
      Young's modulus, the yield strength and the percentage of deformation were
      automatically recorded. There was a statistically significant difference, for the
      three criteria, between the cold and warm gutta-percha. Warm gutta-percha
      presented a Young's modulus 100 times smaller, a yield strength 2 times smaller
      but a percentage of permanent deformation 10 times higher than cold gutta-percha.
      Gutta-percha Hygenic presented the best characteristics.

PMID- 9028197
TI  - Detection of pulse in oral mucosa and dental pulp by means of optical reflection
      method.
AB  - This paper describes a new system in which optical reflectance is used to test
      the pulse and vitality of oral mucosa or dental pulp. Radiation at red (660 nm)
      and near infra-red (850 nm) wavelengths are directed through a thin probe. The
      beam is directed into tissue and reflected back. Plethysmography is used to
      measure the pulse rate from the right forefinger. Reflected radiation is related
      to plethysmogram using a computer. Preliminary findings relating to the lips and
      gingiva in 9 healthy volunteers were promising. Preliminary tests showed that
      vital and nonvital pulps reflected the radiation differently. Pulpal pulse did
      not always correspond to plethysmogram from the right forefinger.

PMID- 9028198
TI  - Dental injuries of permanent teeth treated in private practice in Athens.
AB  - Although there are several epidemiological studies on dental trauma
      internationally, there are not many studies that record, analyse and follow
      different kinds of dental trauma treated in a private office, and that evaluate
      how parameters such as type of dental trauma, as well as time lapse until
      treatment might influence the final outcome and the prognosis of the teeth. The
      sample consisted of 242 patients, 6-17 years of age, with 369 injured teeth
      treated within a period of 5 years. All the case were treated by the first author
      and were followed for at least 3 years. The treatment modalities used were based
      upon the clinical examination and the history of the case and included direct and
      indirect pulp capping, partial pulpotomy, pulpotomy, pulpectomy and splinting.
      The type of trauma was classified based on WHO classification partially modified.
      Seventy six percent of the teeth suffered only hard tissue injuries and 22% had
      only periodontal ligament PDL) trauma. Of the total number of teeth class I
      represented 3%, class II 59%, class III 20% and class IV 2%. Of the PDL injuries
      14% of the teeth suffered concussion, 69% luxation and 17% exarticulation. The
      highest incidence of dental trauma was observed at the age of 10. Sixty eight
      percent of the patients sought treatment 3 days or more after the trauma had
      occurred delayed treatment), while only 32% within the first 3 days (immediate
      treatment). The main reasons for delayed treatment were neglect (50%) and
      unawareness 37%). Of the teeth with delayed treatment 43% became necrotic, while
      only 28% of the teeth that were treated on time needed pulpectomy. Luxations
      caused more pulp necrosis (46%) than Class I (0%) Class II (7%) or Class III
      (34%) type of trauma. The data from this study suggested that a most of the
      dental injuries on permanent teeth were class II or III type, b) a high
      percentage (68%) of the patients sought treatment more than 3 days after the
      injury (delayed treatment), c) delayed treatment caused more necrotic teeth, d)
      the public should be informed of the importance of immediate treatment in an
      effort to improve the prognosis of the pulp, e) dentists should be informed of
      the appropriate treatment of dental injuries since 10.3% of the cases were
      mistreated.

PMID- 9028199
TI  - Anaerobic microorganisms in root canals of human teeth with chronic apical
      periodontitis detected by indirect immunofluorescence.
AB  - Aiming to assess the presence of selected anaerobic microorganisms in root canals
      of human teeth with chronic apical periodontitis. 25 central and lateral upper
      incisors presenting with radiographic evidence of chronic apical periodontitis
      were studied. The pulp chamber was opened under aseptic conditions and samples of
      the root canal content were collected with sterile absorbent paper points, which
      were placed and dispersed in test tubes containing reduced transport medium RTT.
      Aliquots were dried on glass slides and stained by indirect immunofluorescence
      for detection of Actinomyces viscosus, Fusobacterium nucleatum, Porphyromonas
      gingivalis and Prevotella intermedia. The results showed a positive indirect
      immunofluorescence reaction in 24 of the 25 samples. Fourteen were positive for
      the specie Actinomyces viscosus, 12 for Prevotella intermedia, 10 for
      Fusobacterium nucleatum and 4 for Porphyromonas gingivalis. A semiquantitative
      assay was easily implemented for assessment of degree of infection by the
      organisms in individual cases.

PMID- 9028200
TI  - Scanning electron microscopic observations of apical root surfaces of teeth with
      apical periodontitis.
AB  - The aim of this study was to observe apical root surfaces of teeth with chronic
      periapical lesions. Five premolars and three molars with radiographically
      demonstrable periapical lesions were extracted and fixed in 2.5% phosphate
      buffered glutaraldehyde solution for 9 days. The apical 3-mm portion of 17 roots
      was removed and prepared for scanning electron microscope. Lacunar resorption
      zones were frequently observed on the root surfaces. Bacteria and yeast cells
      were detected in some of the lacunae. Periapical bacterial plaque with a smooth
      structure was present mostly around the main apical foramen. Cementum-like tissue
      deposits indicative of repair were seen adjacent to some resorption areas.
      Clastic cells tightly attached to crater-like depressions with finger-like
      projections were observed laterally on the specimens. Current research should be
      focused on new procedures to eliminate extraradicular microrganisms and
      periapical bacterial plaque in persistent periapical infections.

PMID- 9028201
TI  - Taper and stiffness of sonic endodontic files.
AB  - The aims of this investigation were to measure the thickness and taper of the
      different files (Heliosonic 15-40. Shaper 15-40 and Rispisonic 1-6) supplied with
      the MM1500 sonic instrument and relate this to their stiffness. The diameter of
      the files (n = 5 for each file type) was measured at 2 mm intervals using light
      microscopy and a calibrated graticule (mag x 120). A model system was developed
      for the stiffness testing. The file was held 3 mm from its tip and the load in g
      required to produce a 45 degrees deflection of the file was recorded.
      Measurements of file diameter showed that the width of the Heliosonic and Shaper
      increased in a linear manner and that the file taper was the same for increasing
      file sizes in accordance with ISO recommendations. The Rispisonic files however
      showed differing widths and degrees of taper which were not consistent with ISO
      standards. The stiffness testing results showed the Heliosonic files to be less
      flexible than the Rispisonic and Shaper files for all sizes (ANOVA, p < 0.001).
      The differences in stiffness of the Heliosonic, Shaper and Rispisonic files were
      due to the variation in cross sectional area of metal. In conclusion sonic
      endodontic files do not have the same taper and stiffness.

PMID- 9028202
TI  - Surface morphology changes in human enamel, dentin and cementum following
      bleaching: a scanning electron microscopy study.
AB  - Extracted human premolars were cut, cleaned and divided into 6 experimental
      groups. Each group was treated with one of the following bleaching materials: 30%
      hydrogen peroxide, 10% carbamide peroxide, sodium perborate, Nu-Smile,
      Opalescence and DentlBright. Morphological changes in tooth surface occurred
      following treatment with most bleaching agents. Hydrogen peroxide and DentlBright
      were associated with surface changes in all dental tissues. Hydrogen peroxide,
      DentlBright, Nu-Smile and Opalescence were mainly associated with surface changes
      in the cementum, which exhibited more changes than the other tissues.

PMID- 9028203
TI  - Effects of prilocaine local anaesthetic solutions on pulpal blood flow in
      maxillary canines.
AB  - The effects of prilocaine local anaesthetic solutions on pulpal blood flow (PBF)
      in maxillary canines were investigated in nine adult subjects. Buccal
      infiltration of 2 ml of the following solutions were carried out: 3% prilocaine;
      3% prilocaine with 0.03 IU/ml felypressin; and 3% prilocaine with 1:100,000
      adrenaline. Blood flow in the anaesthetized tooth was monitored by a laser
      Doppler flowmeter and data stored in a computer. An electric pulp tester was used
      to assess pulpal anaesthesia. The duration of anaesthesia was recorded. After
      administration of plain prilocaine, PBF changed little throughout the experiment
      in all nine subjects. When prilocaine with felypressin was injected. PBF
      fluctuated greatly, but there was no sustained increase or decrease. In
      comparison, prilocaine with adrenaline caused a significant decline in PBF in
      every subject (p < 0.05), but then gradually started to return to the pre
      injection level: there was no such change in PBF of the contralateral tooth.
      Injection of 3% plain prilocaine achieved a short duration of pulpal anaesthesia
      (median 7 min) in only three subjects. When prilocaine with felypressin was
      injected, eight out of nine subjects experienced pulpal anaesthesia (median
      duration 10.5 min). Injection of prilocaine with adrenaline caused pulpal
      anaesthesia in six of nine subjects (median duration 10.5 min). The use of
      vasoconstrictors with prilocaine anaesthetics had less pronounced effects on
      blood flow and shorter periods of anaesthesia than those reported previously for
      lignocaine with adrenaline.

PMID- 9028204
TI  - Cutting characteristics of a sonic root-end preparation instrument.
AB  - The aim of this study was to investigate the cutting ability of retro tips
      powered by a sonic handpiece (MM 1500, Micro Mega, Prodonta, Geneva,
      Switzerland). Two levels of the following variables were evaluated in this study:
      a) power setting with the an inlet ring half or fully open, b) orientation of tip
      perpendicular or parallel to the long axis of the handpiece, c) length of tip 2
      or 3 min, d) loading of 25 or 50 grams, e) tip size 35 or 55. The substrate used
      was 1 mm thick sections of bovine bone and load was controlled by using a load
      cell interfaced with a transducer meter. Instrumentation time was fixed at 10
      seconds with water irrigation. A 2(5) full factorial analysis was performed with
      two replications making a total of 64 experimental units. The resultant depth of
      cut was measured using a stereo microscope at x50 magnification. Analysis of the
      data indicated that all variables had a significant effect on cutting (ANOVA p <
      0.05). The most significant factor was power, followed by tip length tip
      orientation, width and load. An increase in loading resulted in tip constraint
      and a reduction of cutting at the lower power setting. In conclusion sonically
      activated retro tips were found to cut satisfactorily with instrument air inlet
      ring opening/power having the main effect.

PMID- 9028205
TI  - Effect of retrograde cavity preparations on root apexes.
AB  - Ultrasonic cavity preparations in endodontic surgery has become a popular
      procedure with several advantages noted: Smaller cavities, deeper and cleaner
      preparations, less removal of surrounding bone needed for instrumentation and
      less removal of root apex dentin. Concern has been raised that lines of
      infraction have appeared in some instances when the ultrasonic instruments have
      been used. We wished to examine the result of cavity preparations in root apexes
      using five different methods: high and slow speed handpieces, sonic instruments,
      and ultrasonic instruments at two power settings, medium and high levels,
      respectively. The results showed that all the methods produced some infractions;
      the high power ultrasonics produced the most infractions while the lowest numbers
      were associated with the slow speed handpiece and ultrasonic instruments at the
      medium power setting.

PMID- 9028207
TI  - Oral soft tissue trauma: gingival degloving.
AB  - Ideally gingival degloving following a traumatic episode should be treated as
      soon as possible by repositioning the displaced gingivae and mucosa. The cases
      reported are of degloving in the primary and permanent dentition. In both cases
      immediate assistance was sought from health professionals but no treatment was
      offered. The delay before attendance at the Dental Hospital meant that it was too
      late to offer active treatment. Instead supportive measures were instigated which
      resulted in eventual successful healing.

PMID- 9028206
TI  - Treatment of labial fenestration of maxillary central incisor.
AB  - A case of external inflammatory root resorption and labial fenestration in a
      maxillary central incisor is presented. The root canal was dressed with pure
      calcium hydroxide mixed with normal saline for 1 month before it was obturated
      with gutta percha and apicoectomy surgery undertaken to attempt primary closure
      of the fenestration. The PDL and the fenestration healed uneventfully.

PMID- 9028208
TI  - Prosthodontic management of a combination transosteal/endosteal implant
      reconstruction: a clinical report.
AB  - This is a clinical report of a patient who was not referred for prosthodontic
      evaluation and treatment until after undergoing Branemark endosseous implant
      placement to supplement the previously existing mandibular staple bone plate
      implant. This supplemental treatment was the surgeon's attempt to resolve the
      patient's complaint of loose dentures. Creativity with implant biomechanics and
      prosthodontic design were necessary to restore the patient, in a predictable
      manner, to normal function. A fixed, detachable cast overdenture bar rigidly
      connected to all the implants was constructed utilizing resilient attachments to
      retain the tissue-supported mandibular overdenture. A presurgical prosthodontic
      evaluation could have averted many of the problems encountered with treatment.
      More effective conventional prosthodontic treatment may have resolved the
      patient's complaints and eliminated the need for additional implant placement.

PMID- 9028209
TI  - Factors associated with successful denture therapy.
AB  - PURPOSE: The purpose of this investigation was to evaluate complete denture
      patients at pretreatment and postinsertion, 6 months and 18 months after denture
      delivery in order to develop an explanatory model of successful denture therapy
      to better understand patient acceptance of complete dentures. MATERIALS AND
      METHODS: Sixty complete-denture patients treated at a dental student clinic were
      followed through denture therapy and for 18 months thereafter. Subjects were
      examined and completed pretreatment questionnaires and posttreatment interviews.
      Three outcome measures of denture success were tested, and factors considered
      substantive in achieving a successful denture outcome were examined using
      multivariate analyses. RESULTS: At post-insertion, 76.7% of subjects were
      satisfied with their dentures, 74.6% said their expectations were met, and 66.7%
      said they adjusted easily to their new dentures; reports at 6 and 18 months were
      similarly high. Logistic regression findings suggest that psychological and
      interpersonal factors are more important determinants of denture satisfaction
      than anatomic or clinical factors. CONCLUSIONS: Subject characteristics including
      age, gender, race, income level, education, marital status, and maxillary and
      mandibular anatomy were not significantly associated with denture success as
      defined by the three outcome measures used in this study. Although these
      variables may represent important co-factors in the patient's acceptance of
      dental services and may affect the way a patient perceives dental care outcomes,
      statistically significant relationships were not found within our sample.
      Psychosocial variables, such as pretreatment expectations, satisfaction with the
      dental care received, and mental health showed a stronger relationship to a
      successful outcome.

PMID- 9028210
TI  - A retrospective clinical study of resin-bonded cingulum rest seats.
AB  - PURPOSE: The purpose of this study was to evaluate the success of the resin
      bonded cingulum rest seats (RBCRS) supporting removable partial dentures.
      MATERIALS AND METHODS: Twenty-six patients who had been treated with RBCRSs were
      recalled and examined. RESULTS: None of the patients who had RBCRSs placed on
      their teeth experienced debonding, and none of the teeth showed clinically
      significant signs of wear to the rest seats. CONCLUSIONS: The use of RBCRSs to
      support removable partial dentures is a highly successful method of treatment.

PMID- 9028212
TI  - A comparison of microwave and dry-heat curing methods on the bond strength of
      silicone facial materials applied to acrylic resin.
AB  - PURPOSE: This study compared two curing methods (microwave irradiation and dry
      heat) on the tensile bond strength of silicone facial materials to cured acrylic
      resin. The facial materials studied were Mollomed, Silskin II, MDX4-4210, and A
      2186. MATERIALS AND METHODS: The samples were processed with microwaves for 13
      minutes at 90 W plus 2 minutes at 500 W and dry heat for 3 hours at 100 degrees C
      to cured acrylic resin. Facial materials 3-mm thick were processed between two
      half-dumbbells of acrylic resin. The bonding surfaces were treated with a primer.
      The samples were placed in tension until failure. RESULTS: The results showed
      that the bond strength was affected by the type of silicone material and not by
      the curing methods used. CONCLUSIONS: Mollomed had the highest bond strength of
      all materials tested. MDX4-4210 and A-2186 showed the lowest, and Silskin II had
      intermediate bond strength. Microwave irradiation has the potential of saving
      time, energy, and resources during the fabrication of facial prostheses, but
      further laboratory studies and clinical trials are indicated.

PMID- 9028211
TI  - Contact damage as a failure mode during in vitro testing.
AB  - PURPOSE: The purpose of this study was to identify the failure mode(s) for all
      ceramic crowns tested in vitro and to determine whether measured failure loads in
      this type of testing would be influenced by indenter radii (a classic Hertzian
      cone-crack variable) and specimen thickness. MATERIALS & METHODS: Fracture
      surfaces and failure probability data from glass-ceramic cuspids (n = 50) tested
      in a previous in vitro study were examined to determine their mode of failure. To
      further evaluate the failure mode identified for the crowns, 100 ceramic
      platelets (50 glass-ceramic, 50 feldspathic porcelain) were loaded to failure
      beneath spherical indenters (radii, 0.75-94 mm). RESULTS: Glass-ceramic cuspids
      failed from blunt contact damage at the point of loading (with Hertzian stress
      state damage evident). Ceramic platelets exhibited failure from either the
      indentation surface (Hertzian cone-cracking present) or from the supported
      surface (ie, mimicking bending failure). Failure-loads increased with the
      indenter radius for both failure modes. Failure from blunt contact damage
      occurred at markedly higher loads than did failure from support-surface sites.
      CONCLUSIONS: Blunt indentation damage was identified as being the failure source
      for the glass-ceramic cuspid crowns and a major failure mode for both feldspathic
      porcelain and glass-ceramic platelets loaded beneath spherical indenters. This
      failure mode is not similar to that reported for clinically failed glass-ceramic
      crowns. Influential testing variables were contact radius, ceramic thickness, and
      the surface finish of both the ceramic specimen and test platen.

PMID- 9028213
TI  - Compressive characteristics of an internally threaded post system.
AB  - PURPOSE: The effects of oblique compressive forces were evaluated for extracted
      teeth restored with posts of solid and internally threaded designs. MATERIALS AND
      METHODS: A group of 25 roots was restored with crowns supported by Para-post
      dowels and pin-retained composite resin cores, and a second group was restored
      with gold copings cast to internally threaded stainless steel-post prototypes.
      Samples were then embedded in epoxy resin and loaded at 45 degrees until failure.
      Failure force and type were statistically analyzed to determine statistical
      difference (P < .05) between groups. RESULTS: No statistical difference was shown
      between groups for either fracture force or type. CONCLUSIONS: The internally
      threaded post system resisted oblique loading forces similarly to a solid post
      system.

PMID- 9028215
TI  - Comparison of the in vitro fatigue resistance of an acrylic resin removable
      partial denture reinforced with continuous glass fibers or metal wires.
AB  - PURPOSE: The fatigue resistance of heat-polymerized acrylic resin test specimens
      reinforced with continuous glass fibers or metal wire was investigated. MATERIALS
      AND METHODS: Test specimens in the shape of maxillary removable partial dentures
      were reinforced with one of the following: (1) circular steel wire (cross
      sectional diameter, 1.0 mm); (2) semicircular steel wire (cross-sectional
      diameter, 1.0 x 2.0 mm); or (3) continuous unidirectional E-glass fibers. Ten
      specimens were fabricated for each test group. The specimens were tested by a
      constant force flexural fatigue test at a force of 180 N while immersed in 37
      degrees C water. The number of loading cycles required to generate a fatigue
      fracture and the position of the fracture were measured. RESULTS: Results showed
      that the test specimens, which were either unreinforced or reinforced with metal
      wires, fractured after 13,197 to 39,237 loading cycles. For the glass fiber
      reinforced test specimens, the fracture did not coincide with the region of the
      strengthener but with the opposite side of the test specimen after 1,239,298
      loading cycles. The position of the fracture showed a statistically significant
      variation between the test groups (P < .001). CONCLUSIONS: This study suggests
      that the fatigue resistance of acrylic resin removable partial dentures
      reinforced with glass fibers are superior to those removable partial dentures
      reinforced with conventional metal wire.

PMID- 9028214
TI  - Marginal fit of electroformed ceramometal crowns.
AB  - PURPOSE: A method of fabricating ceramometal crowns using gold copings produced
      by an electroforming process has been described, which purportedly results in
      restorations exhibiting an excellent marginal fit. This study compares the fit of
      electroformed ceramometal crowns with ceramometal crowns fabricated using
      conventional lost wax casting techniques. MATERIALS AND METHODS: Electroformed
      and conventional ceramometal crowns were fabricated for prepared extracted teeth.
      Specimens were cemented, embedded in acrylic resin, sectioned, polished,
      photographed, and measured to compare marginal fit. RESULTS: Marginal fit of
      electroformed ceramometal crowns was superior to the fit of ceramometal crowns
      fabricated using conventional casting techniques. The difference was
      statistically significant at a P = .05 level. CONCLUSIONS: Crowns utilizing
      copings fabricated by electroforming methods appear to have a fit superior to
      conventional ceramometal crowns fabricated using copings made by lost wax
      casting. The ease in laboratory electroforming techniques and the esthetic
      advantages of a gold-colored coping can be capitalized on without concerns of a
      poorer fit.

PMID- 9028216
TI  - Patient-centered competency-based education in fixed prosthodontics.
AB  - Revision of a traditional fixed prosthodontic curriculum was undertaken in
      response to observed private practice patterns, recent literature in fixed
      prosthodontics, and an increasingly crowded dental school curriculum. The
      revision was further motivated by the commitment of the faculty to become patient
      centered in all components of instruction. The resultant preclinical and clinical
      curriculum emphasizes patient care activities and minimizes student-generated
      laboratory products. This program is characterized as patient-driven, competency
      based, and criterion-referenced, and it places heavy reliance on validated
      pedagogical strategies, which include evaluation of self and peers. The
      curriculum requires the development of good communication skills with peers,
      faculty, and commercial laboratories and creates time for the student to develop
      critical patient care skills without requiring more curriculum time. The new
      fixed prosthodontic curriculum appears to be consistent with current private
      general practice, national licensing examinations, and the recommendations of the
      Institute of Medicine's report to dental education.

PMID- 9028217
TI  - A technique for shielding electron beams used in radiotherapeutic management of
      head and neck cancer.
AB  - One of the major complications of radiation therapy in the management of
      maxillofacial tumors is the postradiation damage to the healthy tissues adjacent
      to the tumors. The success of radiation therapy is often limited by the treatment
      sequelae. The use of shielding prostheses reduces the number of potential
      treatment sequelae caused by the administration of therapeutic radiation for head
      and neck tumors. A technique for shielding uninvolved tissues from external
      electron beams used in therapeutic radiation treatment of head and neck cancer is
      described. The materials required are readily available and the shielding
      prosthesis can be easily fabricated by any dentist with a thorough understanding
      of radiation therapy, dosimetry, and the goals of treatment with radiation
      therapy.

PMID- 9028218
TI  - The Institute of Medicine study of dental education: issues affecting
      prosthodontics. Report of the Educational Policy Subcommittee of the American
      College of Prosthodontists.
AB  - In 1993, the National Academy of Sciences' Institute of Medicine (IOM) convened a
      committee to study dental education and to make recommendations regarding the
      future of dentistry. The study was prompted by educational and professional
      concerns: specifically, the number of dental school closures, the high cost of
      dental education, the size of the dental workforce, and the role of dentistry
      within medicine and the health care system. In January 1995, the IOM's Committee
      on the Future of Dental Education concluded "Dental Education at the Crossroads
      Challenges and Change," a 345-page report that includes eight policy and
      strategic principles and presents 22 recommendations. The unabridged text of the
      strategic principles and recommendations is published at the beginning of this
      paper. The IOM text notes impressive achievements in dentistry, and the
      recommendations form a foundation for the assessment of the many crucial issues
      that face dental education and dentistry today. The IOM report urges each dental
      school to review its curriculum and individually determine how best to fulfill
      its missions of education, research, and patient care. As dental education looks
      to the future, the practice of dentistry will be altered by social, economic,
      political, and technological developments as our consumers (students and
      patients) demand professional accountability and effectiveness. In the midst of
      this call for change, the specialty of prosthodontics is faced with many
      challenges and opportunities. This article is the response to a request from the
      American Dental Association (ADA) to address the IOM study on dental education as
      it affects the specialty and practice of prosthodontics. This article presents
      the position of the American College of Prosthodontists (ACP); however, some
      sections have been expanded to provide additional background information.

PMID- 9028219
TI  - Multiple implants for first molar prosthodontics.
AB  - Problems that can occur when single implants are utilized to restore first molar
      teeth include the frequent loosening of screws, as well as screws and/or implant
      breakage. These may result from torquing and rotational movements of the
      prosthesis during masticatory and parafunctional mandibular movements. When
      sufficient bone and mesio-distal restorative space is present, the placement of
      two implants should be considered.

PMID- 9028220
TI  - Esthetics: patients' perceptions of dental attractiveness.
AB  - PURPOSE: The importance of dentofacial attractiveness to the psychosocial well
      being of an individual has been well established. Very little information is
      available regarding dental patient perceptions of a pleasing esthetic image. The
      purpose of this study was to identify factors distinctive to attractive smiles
      versus unattractive smiles, as perceived by patients. MATERIALS AND METHODS:
      Standardized format photographs (5 x 7 in, matte finish, at f-32 and 1:2
      magnification) of eight male and eight female smiles, framing only lips and
      teeth, were viewed by 297 subjects. The smiles exhibited differences in symmetry,
      tooth shade, number of teeth displayed, and height of maxillary lip line, and
      included both restored and unrestored teeth. Respondents ranked the photographs
      in order from most to least appealing appearance. Respondents viewed each series
      of photographs in a similar lighting and time period. A questionnaire identified
      the respondent's age, sex, race, education, income, and home town. Twenty-five
      demographic groups were established from the information in the questionnaire.
      Data were analyzed using stepwise discriminant analysis to determine the
      combination of smile characteristics that best predicted the ranking. RESULTS:
      The same female smile was chosen as the most attractive by 24 of the 25
      demographic groups. This smile is characterized by natural teeth having light
      shade, high lip line, a large display of teeth, and radiating symmetry. Two
      female smiles typified by darker shade and asymmetry were rated by all groups as
      being least attractive. Two male smiles were judged equal as the most pleasing
      esthetically. Respondents favored those smiles characterized by light shade, a
      moderate display of teeth, moderate lip line, and a symmetrical arrangement of
      teeth. One male smile characterized by darker shade was rated as least
      attractive. CONCLUSIONS: In all cases, tooth shade was the most important factor,
      followed in sequence by unrestored natural teeth and number of teeth displayed.
      No correlation was found to exist between specific demographic groups and smile
      variables.

PMID- 9028221
TI  - Geometric analysis of occlusal plane orientation using simulated ear-rod facebow
      transfer.
AB  - PURPOSE: Ear-rod facebow techniques may position casts high or low between the
      upper and lower members on the articulator when using orbitale or nasion as
      anterior reference positions. This study assessed the effect of changing the
      anterior reference position on simulated mountings utilizing simulated ear-rod
      facebow. MATERIALS AND METHODS: Tracings from latoral cephalographs made on seven
      subjects were superimposed with an outline model of a semiadjustable articulator.
      Three simulated mountings were performed for each subject in which the plane of
      occlusion was positioned (1) high, (2) midway, and (3) approaching the lower
      member (low). Maxillary and mandibular occlusal planes representing intercuspal
      position were determined from the cephalographs and positioned on the articulator
      model in a simulated centric relation position for each mounting. Condylar
      guidance was determined from a simulated protrusive position. RESULTS: Analysis
      of the three mounting positions demonstrated no change in intercuspal position
      within subjects; however, angles formed between upper member and condylar
      guidance were 14.9% smaller for the mid-distance mounting, 42.9% smaller for the
      high mounting, and 13.4% higher for the low mounting positions when compared with
      a standard Frankfort horizontal plane reference. CONCLUSIONS: The cephalographs
      showed extreme variability in the position of the ear piece to bony structures of
      the skull, but this deviation appeared to be compensated by a change in the
      horizontal condylar guidance relative to mounting. Results also suggest that
      casts may be mounted in a convenient mid-position for routine articulation.

PMID- 9028222
TI  - Effect of firing on the color stability of a light-cured ceramic stain.
AB  - PURPOSE: This study evaluated the color stability of four stains of a light-cured
      porcelain stain system between the light-cured and fired stages. MATERIALS AND
      METHODS: Thirty-six ceramometal discs 20 mm in diameter and 2 mm in thickness
      were cast to provide the substrate on which Ceramco II porcelain was applied. The
      porcelain was polished to a uniform thickness of 2 mm, and the samples were
      divided into four groups and assigned a color (yellow, orange, green, or blue).
      Orbit LC stain was applied in a thin layer and light-cured for 40 seconds. After
      light-curing, three color readings were made with a Minolta Chroma Meter II. The
      porcelain discs were then fired in a porcelain oven and three color measurements
      were again made. The pre- and postfired Commission Internationale de I'Eclairage
      L*a*b* values were recorded and the color difference (delta E) was calculated for
      each specimen. The clinical significance for the computed delta E ratings was
      completed according to previously modified criteria. RESULTS: The results show
      that the mean delta E between the light-cured and fired stages of Orbit LC are
      clinically acceptable. No statistically significant differences (p < .05) were
      observed between any of the four groups. CONCLUSIONS: A light-cured porcelain
      stain system was evaluated for color stability between light-cured and fired
      stages. Within the conditions of this study, the following conclusions can be
      made: (1) There was no clinically significant color difference between light
      cured and fired stages for the stain colors evaluated; and (2) the final color of
      the restorations altered with light-cured stains can be predicted before firing.

PMID- 9028223
TI  - Fatigue resistance and stress of wrought-steel wire clasps.
AB  - PURPOSE: The objective of this study was to determine the fatigue resistance of
      wrought-steel wire clasps used for removable partial dentures. MATERIALS AND
      METHODS: Five wrought-steel wires with cross-sectional diameters of 1.2, 1.1,
      1.0, 0.9, and 0.8 mm were tested using a deflection fatigue test with deflections
      of 0.4 to 0.7 mm. The force and stress required to cause deflection was
      determined, as well as the number of loading cycles required to cause fatigue
      fracture. The fracture surfaces of the wrought-steel wire clasps were examined
      with a scanning electron microscope. RESULTS: The number of loading cycles
      required to cause fatigue fracture increased with reduced deflection of the
      wrought wire (p < .005). To obtain fatigue resistance for loading cycles of over
      10(6), the stress in the wrought-steel wire clasp should remain under 1.0 GPa.
      CONCLUSIONS: These results suggest that to avoid fractures of wrought-steel wire
      clasps caused by bending fatigue, the stress on the clasp during its deflection
      should be taken into account.

PMID- 9028224
TI  - Comparison of strains transferred to a bone simulant between as-cast and
      postsoldered implant frameworks for a five-implant-supported fixed prosthesis.
AB  - PURPOSE: To measure and compare the strains transferred by screw-fastening one
      piece full-arch prostheses as cast and after sectioning and soldering. MATERIALS
      AND METHODS: Photoelastic resin was applied directly to five 3.75 x 13-mm
      Branemark implants, situated 7 mm apart, in a silicone mold of an edentulous
      mandible. Four strain gauge rosettes were also incorporated in the resin to allow
      strain measurements at four locations. Three frameworks were made from a single
      master cast produced from an impression of the five-implant model with 4-mm
      abutments. These frameworks were sequentially secured to the master model with
      five gold slot screws tightened to 10 N cm. Strain indicator readings were
      recorded at a standardized time following the initial fastening of each
      prosthesis. The test was repeated three times. Each of the three castings were
      subsequently sectioned and soldered in two locations, mesial to the two terminal
      fixtures. After soldering, the three superstructures were returned to the master
      model for measurement of postsolder strains three times each. A one-way repeated
      measures ANOVA was performed to determine differences between mean principal
      strains between the as-cast and postsoldered groups. RESULTS: A statistically
      significant difference was found in the principal strains between the as-cast and
      soldered frameworks. Overall, there was a decrease in the magnitude of strain for
      the soldered frameworks. CONCLUSIONS: Sectioning and soldering improved the as
      cast accuracy as far as the amount of strain transferred to the bone simulant.

PMID- 9028225
TI  - Accuracy of wax, autopolymerized, and light-polymerized resin pattern materials.
AB  - PURPOSE: The marginal fit of MOD inlay and full-crown patterns fabricated from
      wax, autopolymerized acrylic resin, and two light-polymerized, diacrylate resin
      pattern materials was compared on standardized dies. MATERIALS AND METHODS: Four
      pattern materials were studied-two light-polymerized, diacrylate resin materials
      (Palavit G LC and Triad VLC Burnout Paste), an inlay wax, and an autopolymerized
      resin (Duralay). Patterns were fabricated using incremental and bulk techniques
      on stone dies made from addition silicone impressions of American Dental
      Association MOD and full-crown master dies. Gaps were measured with a measuring
      microscope in four marginal areas on the master dies at 1 and 24 hours after
      fabrication. RESULTS: For the MOD inlay patterns, marginal gaps ranged from 7 to
      23 microns, and the light-polymerized, diacrylate resins and autopolymerized
      acrylic resin material had statistically smaller gaps than the inlay wax. For the
      full-crown patterns, marginal gaps ranged from 10 to 23 microns, with the
      exception of the autopolymerized acrylic resin prepared by the bulk technique (40
      to 46 microns). With the incremental technique, the light-polymerized, diacrylate
      resins and inlay wax had statistically smaller gaps than the autopolymerized
      acrylic resin material. Overall, the incremental technique produced equal or
      smaller marginal gaps than the bulk technique for full-crown patterns. Generally,
      the patterns measured at 1 hour had smaller marginal gaps than at 24 hours.
      CONCLUSIONS: When measured on intra- and extracoronal master dies, the light
      polymerized, diacrylate resins had equal or better marginal fit, compared with
      wax or autopolymerized acrylic resin, and were less affected by placement
      technique and storage. The marginal gaps of all four pattern materials ranged
      from 7 to 46 microns and are within the range of clinical acceptability.

PMID- 9028226
TI  - The Periotest method: implant-supported framework precision of fit evaluation.
AB  - PURPOSE: In this study, the Periotest instrument was used to measure the
      precision of fit between cast high noble-metal frameworks and the supporting
      implants in a patient-simulation model. Three framework conditions and three
      implant-location variables were used to evaluate the rigidity of the assembly as
      measured by the Periotest method. The framework variables were (1) one-piece
      castings (OPC); (2) sectioned-soldered inaccurate castings (SSIC); and (3)
      sectioned-soldered accurate castings (SSAC). The implant-location variables were
      right anterior (RA), center (C), and left anterior (LA). MATERIALS AND METHODS:
      The patient simulation model used consisted of three self-tapping Branemark
      implants in a reasonable arch curvature in bovine bone. Three working casts were
      fabricated from the patient-simulation model using polyvinyl siloxane and tapered
      impression copings. From the working casts, three sets of three frameworks were
      fabricated as OPCs, SSICs, and SSACs using type 3 high noble alloy. The SSICs
      were fabricated with a quantitative misfit of 101.6 microns at the facial
      surface, between the abutment-to-gold cylinder interface at the C implant
      location. Periotest value (PTV) measurements were made at the midfacial surface
      of the frameworks directly above each abutment-to-gold cylinder interface. Three
      measurements were made for each test condition. The data were analyzed to compare
      framework condition(s) and implant location(s) using ANOVA and Fisher's Protected
      Least Significant Difference Comparison Test. RESULTS: The ANOVA showed that
      significant differences exist between the mean PTV data for framework condition
      and for implant location (p < .01). Significant differences were shown between
      the mean PTV data for the SSAC assemblies and the OPC and SSIC assemblies. The
      SSICs displayed a more positive (+) mean PTV than the OPCs. The OPC assemblies
      had a more positive mean PTV than the SSAC assemblies. The mean PTV data for the
      SSAC assemblies had a significantly different PTV (p < .01) than the other two
      framework condition assemblies. The OPC and the SSIC assemblies had PTVs that
      were not significantly different. The C implant location was significantly
      different from the RA and the LA implant locations (p < .01). The RA and the LA
      implant locations were not significantly different from each other. The C implant
      location always demonstrated the most positive mean PTV regardless of the
      framework condition being tested. CONCLUSIONS: The Periotest instrument
      quantified differences in the precision of fit between three framework
      conditions. The SSAC assemblies were significantly more rigid than the OPC and
      SSIC assemblies. The OPC and SSIC assemblies' mean PTVs were not significantly
      different. The mean PTVs for the C implant location and the RA and LA implant
      locations were significantly different (p < .01). The mean PTVs of the RA and LA
      implant locations were not significantly different. The implant-location PTVs
      followed the same rank order for all three framework conditions. The procedures
      used to fabricate a more precise fit between the framework and the supporting
      implants is influenced by the skill of the clinician and technician.

PMID- 9028227
TI  - A seminar/case-based approach to teaching removable partial dentures to
      predoctoral students.
AB  - This article describes a seminar/case-based, instructional model designed to
      simulate removable partial denture (RPD) problem-solving and decision-making
      processes encountered in third-year clinic in dental school and in dental general
      practice. Groups of approximately 20 second-year students (in the 3-year program)
      meet in a series of six 1-hour seminars during the first days of the course.
      Following the seminars, students complete an exercise on mouth preparation and
      multiple clasp and major connector designs on prototype casts. This is followed
      by survey-design exercises on casts of dentitions representing six variations of
      RPD requirements. Instructors assist students during the practice phase of each
      class. Each 2-hour practice session is followed by a 1-hour practical
      examination. The last day of the course is devoted to a comprehensive final
      practical examination on both maxillary and mandibular casts, incorporating any
      of the design features previously studied.

PMID- 9028228
TI  - The results of a brief survey of complete denture prosthodontic techniques in
      predoctoral programs in North American dental schools.
AB  - A brief mail survey of North American dental schools was undertaken to ascertain
      the current techniques in complete denture prosthodontics regarding preliminary
      and final impressions, record bases, and denture teeth. Of the 64 schools
      surveyed, 54 responded (84%). Seventy-four percent of the respondents used only
      irreversible hydrocolloid (alginate) for their preliminary impressions; 15% used
      only modeling plastic impression compound. Eighty-one percent used only modeling
      plastic impression compound for border molding of the final impression tray; 7%
      used only polyether impression material. Forty-eight percent used only
      polysulfide rubber (PR) impression material for their final impression material;
      4% used only polyether impression material. Only 1 school still used shellac as
      one of its materials for record bases. Thirty-five percent used only Triad; 35%
      used only acrylic resin; 24% used both of these materials. Thirteen percent of
      responding schools used only nonanatomic teeth. The majority (54%) used all three
      options (nonanatomic, semianatomic, and anatomic). Eleven percent used
      lingualized occlusion. As compared with a survey performed in 1985, the use of
      irreversible hydrocolloid as a preliminary impression material, the use of
      visible light-cured resins for record bases, and the use of anatomic teeth have
      increased. The use of plastic impression compound for border molding and PR as
      the final impression material has largely remained the same.

PMID- 9028229
TI  - Controlled retainer-screw access placement for screw-retained implant prosthesis.
AB  - An implant-supported prosthesis is often secured to the underlying gold cylinders
      by retaining screws. There must be access to these screws from the oral surface
      of the prosthesis. Conventional preparation of this access is from the oral
      surface. This approach is difficult because the underlying gold cylinder is
      obscured. It may be damaged by a rotary cutting instrument as the access is
      prepared above it, because the cylinder cannot be seen during the preparation.
      Alternatively, the access hole may be unnecessarily enlarged in an attempt to
      find the cylinder. This loss of structure may weaken the prosthesis. A new
      approach, using 18-gauge stainless steel wire as a rotary cutting instrument,
      permits preparation of the access chamber from the intaglio surface of the
      prosthesis. This reduces risk of damage to the gold cylinder and is less
      destructive to the overlying material.

PMID- 9028231
TI  - Decisions of practitioners regarding placement of amalgam and composite
      restorations in general practice settings.
AB  - This study was undertaken to analyze the current reasons practitioners in general
      practice settings choose to place amalgam and composite restorations. Data were
      gathered on individual restorations in the clinical setting to provide
      information on reasons practitioners state that restorations are placed, the type
      of material most often placed in different restoration classifications, and the
      age of restorations at the time of replacement. The results of this study
      indicate that approximately one-half of all restorations, both amalgam and
      composite, were placed to treat primary caries. One-half of the remaining
      restorations placed, i.e., not including those with primary caries, were placed
      to treat recurrent caries. With respect to restorative materials, amalgam was
      most often placed in class 1 and class 2 situations (88.9% of the amalgam
      restorations reported), while composite was most often placed in class 3, 4, or 5
      situations (77.4% of the composite restorations reported). From the total data
      set returned for replaced restorations, only 20% of the data forms reported on
      verified longevity of the restoration being replaced. Analysis of these data gave
      a calculated median longevity for amalgam and composite restorations of 10 years
      and 5 years respectively.

PMID- 9028230
TI  - Bond strength of glass ionomers to coronal and radicular dentin.
AB  - A study was conducted to compare the shear bond strength of a glass-ionomer
      cement and glass-ionomer base to coronal and radicular dentin. Two different
      glass ionomers were bonded to paired coronal and radicular human dentin surfaces
      that had received no surface treatment or had been treated passively for 20
      seconds with either 40% or 25% polyacrylic acid. When only the effect of the type
      of dentin surface was considered, glass-ionomer bonds were greater to radicular
      dentin than to coronal dentin. With one exception, bond strengths to both dentin
      surfaces were greater with the base ionomer (Ketac-Bond) than with the luting
      cement (Ketac-Cem). Bond strengths of both glass ionomers were greater after
      dentin surface treatment with either 25% or 40% polyacrylic acid than with no
      treatment.

PMID- 9028232
TI  - Microleakage in facial and lingual Class 5 composite restorations: a comparison.
AB  - The purpose of this in vitro study was to determine if there is a difference in
      microleakage between facial and lingual enamel and cementum using two different
      evaluation techniques. Class 5 preparations were made in 50 teeth on the facial
      and lingual tooth surfaces and restored using dentin bonding and composite resin.
      The teeth were thermocycled, silver nitrate stained, and longitudinally sectioned
      into mesial and distal halves through each restoration. The mesial half was
      scored using a rank order system. A Kruskal-Wallis one-way ANOVA was performed.
      The distal half was scored by measurement, and a two-sample t-test was performed.
      There were no statistically significant differences (P > or = 0.05) in
      microleakage between facial and lingual tooth enamel or cementum surfaces using
      either measurement technique.

PMID- 9028233
TI  - Trends in elastomeric impression materials.
AB  - In the past three years more addition silicones have been supplied as hydrophilic
      materials and heavier viscosities have been provided in automatic mixing
      cartridges. Also, a polyether is now supplied in an automatic mixing system.
      There has been an increase in the number of products available as monophase or
      single viscosity systems. Both addition silicones and polyethers are available as
      bite registration materials.

PMID- 9028234
TI  - The effects of varied etching time and etching solution viscosity on bond
      strength and enamel morphology.
AB  - The effects of varied etching time and etching solution viscosity on bond
      strength were evaluated by measuring the tensile bond strength of a composite
      resin to bovine enamel. Also, six enamel surfaces were examined to evaluate the
      effect of acid treatment on the morphology of etched enamel using scanning
      electron microscopy. There was no significant difference in tensile bond strength
      between three etchants of differing viscosity or between etch times. Light
      microscopy revealed that most bond failures were cohesive in nature. When the
      three etchants of differing viscosity were compared under the scanning electron
      microscope, the liquid and the thin gel produced a more even etch pattern than
      the thick gel. In addition, the thin gel appeared to produce the most well
      defined pattern of the three conditioners.

PMID- 9028236
TI  - The three kinds of dental schools.

PMID- 9028237
TI  - A modified matrix technique for the application of restorative materials on the
      facial surfaces of teeth.
AB  - A Tofflemire matrix is modified and is secured in place with the help of Super
      Floss and unfilled light-activated resin or light-activated impression material.
      The matrix prevents excess cementing medium escaping in the gingival area,
      providing excellent isolation. The technique is simple and provides good
      esthetics while minimizing lengthy and traumatic finishing procedures.

PMID- 9028235
TI  - The effect of dentin surface moisture on bond strength to dentin bonding agents.
AB  - This in vitro study compares the mean shear bond strengths of two dentin bonding
      agents to dry and to moist human dentin. The occlusal surfaces of 60 extracted
      human molars were ground to produce flat dentin surfaces. The teeth were divided
      into four groups of 15 specimens each. For Scotchbond Multi-Purpose dentin
      bonding agent, the teeth were etched, rinsed, and then either blotted with gauze,
      which left the dentin moist, or dried with compressed air. The primer and
      adhesive were then applied, and composite cylinders were bonded to the teeth. For
      Optibond, the teeth were again either blotted with gauze or dried with air. The
      primer and dual-activated adhesive were applied, and composite cylinders were
      bonded to the teeth. After storage in room-temperature distilled water for 48
      hours, the specimens were thermocycled. Shear bond strength testing was performed
      at 1 week. Analysis using two-sample t-tests found no significant difference for
      either product in bond strengths to moist and to dry dentin (P > 0.05). This
      study indicated that for some current-generation dentin bonding agents, the
      presence of moisture on dentin surfaces does not compromise short-term bond
      strength.

PMID- 9028238
TI  - Saliva contamination of dentin bonding agents.
AB  - This study examined the shear bond strength to dentin of two dentin bonding
      agents when contaminated with a measured amount of saliva at various stages in
      their application procedure. Eighty extracted human third molar teeth were
      randomly separated into four groups of 10 for each of the dentin bonding systems
      tested (All-Bond 2, Scotchbond Multi-Purpose). Group A specimens were not
      contaminated; primer/adhesive/resin were applied according to manufacturers'
      instructions. In Group B, samples were contaminated for 15 seconds with fresh
      whole human saliva, and then forcibly dried with a blast of oil-free air; this
      occurred after application of the primer but prior to application of adhesive. In
      Group C, contamination occurred after application of adhesive, prior to
      application of resin. In Group D, saliva was allowed to contaminate the surface
      as the primer was being applied, without forcible removal. Specimens were then
      thermocycled, mounted, and tested in shear on an Instron at 7 days. Bond
      strengths in MPa were obtained, and data were analyzed using a one-way ANOVA, at
      the P = 0.05 level of significance. Although shear bond strengths were lowered in
      saliva-contaminated samples, there was no statistically significant difference
      between group means.

PMID- 9028240
TI  - Effects of secondary curing on indirect posterior composite resins.
AB  - This study was designed to compare strength, elastic modulus (stiffness), and
      hardness for five composite resin materials that are used for laboratory
      fabricated posterior composite restorations. Ten specimens of each material were
      processed according to the manufacturer's instructions. Statistical analysis
      indicated that there were significant differences in mechanical properties among
      the materials tested. In addition, materials that are incrementally light cured
      prior to secondary processing were tested for changes in mechanical properties
      following secondary processing. It was determined that secondary processing
      provided improvement in flexural strength (11%) when compared to samples that
      were only light cured.

PMID- 9028239
TI  - The effect of various bases on the fracture resistance of amalgam.
AB  - This study compared the compressive force required to fracture amalgam over nine
      base materials: a calcium hydroxide product (Dycal); two autocured glass ionomers
      (GlasIonomer Base Cement and Ketac-Bond); three light-cured glass ionomers
      (Photac-Bond, Variglass VLC, and Vitrebond); two light-cured resins (Timeline and
      VLC Dycal); and a zinc phosphate cement (Fleck's Zinc Cement). For the control
      group, 10 aluminum dies (25 mm x 12 mm x 10 mm) were milled with 3.0 mm x 3.0 mm
      slots, which were filled with hand-condensed Tytin amalgam with no underlying
      base. For experimental groups, 10 aluminum dies of equal dimension were milled
      with 3.5 mm x 3.0 mm slots. Following manufacturer's instructions, the nine base
      materials were successively placed in these 10 dies using a depth-limiting device
      made of light-transmitting clear acrylic to ensure a 0.5 mm thickness, and Tytin
      amalgam was again condensed over each base such that the depth of the amalgam
      equalled that in the control. All test specimens were stored in 100% humidity for
      48 hours then fractured in compression on an Instron machine. Mean force, in
      Newtons (S D in parentheses), required to fracture the specimens was: CONTROL:
      1934(210), Zinc Cement: 1874(147), GlasIonomer Base Cement: 1839(174), Ketac
      Bond: 1723(225), Vitrebond: 1485(155), Photac-Bond: 1422(294), Advanced Formula
      II Dycal: 1296(237), VLC Dycal: 1035(116), Variglass: 909(294) and Timeline:
      906(275). ANOVA and Student-Newman-Keuls statistical analysis (alpha = 0.05)
      indicated that the autocuring glass ionomers, GlasIonomer Base Cement and Ketac
      Bond, and a zinc phosphate cement, Zinc Cement, provided significantly more
      fracture resistance for amalgam than the other bases tested and were not
      statistically different from a no-base control.

PMID- 9028241
TI  - Verification and maintenance of dental explorer sharpness.
AB  - An ongoing study of the relationship between different chewing gums,
      remineralization, and caries rates was started in 1989 in Belize, Central
      America. Initially 1277 children, age 10 years, were assigned in equal randomized
      groups to four dentists who had been trained to identify a standard of caries
      diagnosis. The same children were examined according to a modified WHO caries
      code by the same dentist in each of the three subsequent years. To eliminate one
      possible variable, all 200 dental explorers used were examined under a X20
      binocular Bausch and Lomb dissecting microscope initially and at each exam
      period. Any explorer not comparable to an explorer that was originally marked and
      kept unused as a standard was sharpened by hand on an Arkansas oilstone wetted
      with engine oil for lubrication. Explorers that could not be restored to a
      condition comparable at X20 to the standard were discarded. Approximately 10% of
      the explorers needed correction at each exam period and about 1% were discarded.
      In any study related to dental caries evaluation with dental explorers or
      comparison of explorer use versus nonuse, verification and maintenance of
      sharpness of used and even new dental explorers should be addressed to remove
      that factor as a possible variable.

PMID- 9028242
TI  - Amalgam shear bond strength to dentin using different bonding agents.
AB  - This study evaluated the shear bond strength of amalgam to dentin using five
      different bonding agents: Amalgambond Plus, Optibond, Imperva Dual, All-Bond 2,
      and Clearfil Liner Bond. Flat dentin surfaces obtained by grinding the occlusal
      portion of 50 human third molars were used for this study. To contain the amalgam
      on the tooth surface, cylindrical plastic molds were placed on the dentin and
      secured with sticky wax. The bonding agents were then applied according to the
      manufacturers' instructions or light activated and Tytin amalgam was condensed
      into the plastic molds. The samples were thermocycled and shear bond strengths
      were determined using an Instron Universal Testing Machine. Analysis by one-way
      ANOVA indicated significant difference between the five groups (P < 0.05). The
      bond strength of amalgam to dentin was significantly higher with Amalgambond Plus
      using the High-Performance Additive than with the other four bonding agents.

PMID- 9028243
TI  - Placement and replacement of amalgam restorations in Germany.
AB  - From 15 September to 15 October 1991, 102 dentists practicing in a rural area of
      Germany provided information on 5240 amalgam restorations. The aim of the present
      cross-sectional study was to investigate the reasons for placement and
      replacement of amalgam fillings and to register the age of the failed
      restorations. First placements because of primary caries were made in 47.1% of
      all cases; 52.9% were replacements of failed restorations. The most frequently
      recorded reason for replacement was secondary caries, irrespective of size of the
      filling, dentition, and age group. The second most frequently recorded reasons
      for replacement depended on the size of the filling, the age and the dentition of
      the patient: Bulk fractures were predominant in primary teeth and in fillings
      with three or four surfaces, primary caries in permanent teeth of patients 16
      years old or younger and marginal gaps in adults and in fillings with one or two
      surfaces. The median age of replaced amalgam restorations in adults was 60
      months.

PMID- 9028244
TI  - Dental benefits: essential and important.

PMID- 9028245
TI  - Buonocore Memorial Lecture. Glass-ionomer cements: past, present and future.
AB  - It was Michael Buonocore who focused the attention of the profession on adhesion
      in the oral cavity. He expanded the concept of adhesion of resins to enamel and
      investigated adhesion to dentin. The problem has been solved through the glass
      ionomer cements rather than with resins, but sadly, he did not live to see them
      achieve maturity. The glass-ionomer cements were introduced to the profession in
      1976, and they provide adhesion to both enamel and dentin through an ion exchange
      with the additional benefit of a continuing fluoride release throughout the life
      of the restoration. Solubility is low, abrasion resistance is high, and
      biocompatability is excellent. As a water-based material, they have an excellent
      chance of survival in the hostile environment of the oral cavity. Acceptance of
      the early versions was slow because of perceived problems with water exchange, a
      poor color range, and a lack of translucency. Considerable research has been
      carried out over the last 20 years by members of the profession and the
      manufacturers; at this point, the glass-ionomer cements make a very valuable
      contribution to everyday practice. They are now available as both an autocure and
      a dual-cure cement, and the color range and translucency are excellent. Problems
      of clinical placement have been overcome, and it is now a simple matter to take
      advantage of the adhesion and the fluoride release and place a restoration that
      is esthetic, resistant to microleakage, long lasting, and a deterent to recurrent
      caries. Their only limitation lies in the fact that they lack the fracture
      strength to rebuild marginal ridges and incisal corners. In spite of this
      limitation, they have opened the way for the introduction of a new range of
      microcavity designs that allow for conservation of remaining tooth structure to
      an extent never before available. In the near future physical properties will be
      improved still further, and the use of these cements will expand considerably.

PMID- 9028246
TI  - In vitro inhibition of marginal caries-like lesions with fluoride-containing
      amalgam.
AB  - Carious lesions surrounding restorations represent one of the main causes of
      restoration failure. The addition of fluoride compounds to dental restorative
      materials prevents or reduces recurrent caries. The purpose of this study was to
      compare the capacity of three restorative materials to inhibit the development of
      recurrent caries in vitro. Thirty unrestored, noncarious premolars that were
      being extracted for orthodontic reasons were sectioned in half buccolingually and
      divided into three groups. One of the groups was restored with conventional
      amalgam. The second group was restored with a fluoride-containing amalgam, and
      the third group was restored with a glass-ionomer cement. All the samples were
      submitted to a medium containing Streptococcus mutans (Ingbritt strain) for 8
      weeks. At the end of the 8-week incubation period, the samples were cut into 100
      microns sections, soaked in Quinoline (IR = 1.62), and observed with light
      transmission and polarized light microscopy. The development of artificial caries
      in the cavity walls was measured in microns. The results show that conventional
      amalgam had an average caries penetration of 160 microns, fluoride-containing
      amalgam 46 microns, and glass-ionomer cement 11 microns. Glass-ionomer cement
      gave the best protection against recurrent caries.

PMID- 9028247
TI  - In vitro comparison of filled and unfilled universal bonding agents of amalgam to
      dentin.
AB  - In this study, four different adhesive amalgam systems were compared(Amalgambond
      Plus, Amalgambond Plus with HPA, All-Bond 2, and All-Bond 2 with Liner-F)
      regarding their ability to bond amalgam to freshly prepared dentinal surfaces.
      The two groups that yielded the highest mean bond strengths, Amalgambond Plus
      with HPA and All-Bond 2 with Liner-F, were the only two groups in comparison that
      were not statistically different (P > 0.05). The use of the filled resin bonding
      agents created significantly higher bond strengths between tooth and freshly
      triturated amalgam than the unfilled resin bonding agents. Further study is
      required to determine: a) the exact nature and mechanism of the bonds, and b)
      clinical in vivo presence and longevity of the bonds.

PMID- 9028248
TI  - Bite registration using impression plaster.

PMID- 9028249
TI  - The antimicrobial action of chlorhexidine-containing zinc-phosphate cement.
AB  - In this study chlorhexidine dihydrochloride and diacetate salts were incorporated
      at a low level into a zinc-phosphate luting cement. Inhibition of three
      cariogenic organisms by cement specimens aged up to 8 weeks was significantly
      greater than the bacterial inhibition of unaltered zinc-phosphate cement. The
      addition of chlorhexidine caused no significant degradation in strength, film
      thickness, or solubility of the cement.

PMID- 9028250
TI  - Fracture toughness of pin-retained class 4 restorations.
AB  - Standardized class 4 cavities were prepared in bovine incisors and restored with
      a microfilled composite resin. The composite restorations were retained either by
      acid etching technique (AET) alone or by acid etching technique in combination
      with a self-threading retentive pin. Pins covered with a bonding/opaquer coating
      (PCR pin) and uncovered pins (FO pin) were used. After having been aged for 3
      days, the fracture resistance of the restorations was determined with a Universal
      Testing Machine. The restorations were loaded at an angle of 45 degrees. The
      restorations retained by AET and a PCR pin showed the highest failure load. The
      restorations accomplished with AET and a FO pin yielded the lowest fracture load.
      The fracture toughness of the restorations retained by AET and a PCR pin was
      slightly but statistically significant, higher compared to the restorations
      exclusively attached by acid etching technique. It was concluded that there was
      only a small increase of fracture toughness of large class 4 composite
      restorations if the acid etching technique was combined with the application of
      bonding/opaquer-covered retentive pins.

PMID- 9028251
TI  - The effect of pulpal fluid flow on tensile bond strength of a glass-ionomer
      cement: an in vivo and in vitro comparison.
AB  - Previous studies of the bonding capabilities of glass-ionomer cements have
      concentrated on the use of in vitro testing conditions. Since early moisture
      contamination appears to have adverse effects on the physical properties of glass
      ionomer cements, and with the probability of pulpally derived dentinal fluid
      being present under in vivo conditions, the objective of this study was to
      compare in vivo tensile bond strength with in vitro tensile bond strength of a
      glass-ionomer cement to dentin utilizing the same teeth under similar test
      conditions. A glass-ionomer lining cement was placed on freshly exposed labial
      dentin of the maxillary incisor on 10 Rhesus monkeys. Immediately following
      placement, an orthodontic button was placed over the cement and left undisturbed
      for 1 hour. The teeth were then extracted and stored in 100% relative humidity
      for 23 hours. An Instron testing machine was used to register in kilograms the
      force required to cause tensile bond failure of the cement. Identical methodology
      was then used on the same teeth for in vitro testing. The concluding results
      indicate that a statistically significant difference (P < or = 0.05) exists
      between in vivo and in vitro tensile bond strengths of the glass-ionomer lining
      cement and that the bond failure was cohesive in character for all cases both in
      vivo and in vitro. These findings suggest that clinically, tensile bond strengths
      of glass-ionomer cements to cut dentin can be expected to be weaker in vital
      teeth than in devital teeth.

PMID- 9028252
TI  - Detection of human viruses in periodontal pockets using polymerase chain
      reaction.
AB  - Even though viruses have been implicated in the etiology of several medical and
      dental disorders, little or no data are available on the possible involvement of
      human viruses in the pathogenesis of human periodontal disease. This study
      investigated the presence of human cytomegalovirus, Epstein-Barr virus, herpes
      simplex virus, human papillomavirus and human immunodeficiency virus (HIV) in
      crevicular fluid samples from 30 patients with advanced periodontitis and 26
      subjects with gingivitis. Viral identification was performed on direct
      subgingival samples from 3 diseased sites in each patient using the polymerase
      chain reaction technique. Seventy-eight percent of advanced periodontitis
      patients were positive for at least one of the five test viruses. Cytomegalovirus
      was detected in 60% of the periodontitis patients, Epstein-Barr virus in 30%,
      herpes simplex virus in 20%, human papillomavirus in 17% and HIV in 7%. Forty
      percent of the periodontitis patients revealed coinfection by 2 to 5 viruses.
      Only 31% of the gingivitis subjects showed a positive viral identification in
      crevicular fluid, and infected individuals only revealed human cytomegalovirus.
      This study demonstrated that human viruses may occur in periodontitis lesions
      with relatively high prevalence. The pathogenetic significance of human viruses
      in destructive periodontal disease needs to be determined.

PMID- 9028253
TI  - Direct detection of Streptococcus mutans in human dental plaque by polymerase
      chain reaction.
AB  - Streptococcus mutans is an etiological agent in human dental caries. A method for
      the detection of S. mutans directly from human dental plaque by polymerase chain
      reaction has been developed. Oligonucleotide primers specific for a portion of
      the dextranase gene (dexA) of S. mutans Ingbritt (serotype c) were designed to
      amplify a 1272-bp DNA fragment by polymerase chain reaction. The present method
      specifically detected S. mutans (serotypes c, e and f), but none of the other
      mutans streptococci: S. cricetus (serotype a), S. rattus (serotype b), S.
      sobrinus (serotypes d and g), and S. downei (serotype h), other gram-positive
      bacteria (16 strains of 12 species of cocci and 18 strains of 12 species of
      bacilli) nor gram-negative bacteria (1 strain of 1 species of cocci and 20
      strains of 18 species of bacilli). The method was capable of detecting 1 pg of
      the chromosomal DNA purified from S. mutans Ingbritt and as few as 12 colony
      forming units of S. mutans cells. The S. mutans cells in human dental plaque were
      also directly detected. Seventy clinical isolates of S. mutans isolated from the
      dental plaque of 8 patients were all positive by the polymerase chain reaction.
      These results suggest that the dexA polymerase chain reaction is suitable for the
      specific detection and identification of S. mutans.

PMID- 9028254
TI  - Three subtypes of the tet(M) gene identified in bacterial isolates from
      periodontal pockets.
AB  - The tet(M) genes were characterized from 84 isolates of 10 different bacterial
      species isolated from the periodontal pockets of 16 patients with periodontal
      disease. A 740 bp polymerase chain reaction product from the hypervariable region
      of the tet(M) structural gene was cleaved with the restriction enzymes AluI and
      HinfI. Three different restriction patterns were identified for each of the two
      enzymes. By DNA sequencing, using a direct solid-phase automated sequencing
      method, the isolates could be grouped into 3 different clusters of tet(M)
      subtypes. The internal DNA homology within each subtype was 98-100%; the homology
      between clusters was 89-94%. Two different subtypes were identified in 9 of 10
      bacterial species, and the remaining species had 3 different subtypes. One of the
      subtypes (M3) was seen mainly in the anaerobic isolates. This subtype was
      different from all earlier sequenced structural tet(M) genes present in the
      Genbank. Most patients had two different subtypes of tet(M), and a third subtype
      was seen in the 3 patients who exhibited the greatest variety of tetracycline
      resistant bacterial species. It appears that the presence of one subtype of the
      tet(M) gene within a patient or bacterial species does not prevent the
      acquisition of another subtype of the same gene. This study identified a new
      subtype of the tet(M) gene and grouped it into 3 distinct yet highly homologous
      genetic subtypes.

PMID- 9028255
TI  - Tetracycline resistance in Prevotella isolates from periodontally diseased
      patients is due to the tet(Q) gene.
AB  - Tetracycline-resistance in gram-negative periodontal bacteria is often due to the
      presence of the tet(Q) gene. In the present study the polymerase chain reaction
      (PCR) was used to examine 54 isolates of gram-negative anaerobic rods (Prevotella
      intermedia, Prevotella nigrescens and related or Bacteroides-like species) for
      the presence of the tet(Q) gene. The isolates were recovered from 42 patients
      with periodontal disease living in northern Europe and North America. An 814 base
      pair segment of the tet(Q) gene was amplified from all 41 isolates resistant to
      tetracycline with minimal inhibitory concentrations of 4 micrograms/ml and above.
      The presence of the tet(Q) gene was verified using hybridization with a specific
      oligonucleotide internal to the amplified region and restriction endonuclease
      digestion with DdeI. A PCR product of the same size was also amplified from one
      tetracycline susceptible isolate (minimal inhibitory concentration = 0.5
      microgram/ml). However, this isolate and the one isolate that was resistant to
      tetracycline at 4 micrograms/ml showed a weaker signal than the remaining
      isolates when hybridized with the internal probe. Typing of the PCR products
      using restriction endonuclease digests with AluI and HpaII revealed two clusters
      of distinct electrophoresis patterns, indicating that two different subtypes of
      the tet(Q) gene were present in this material. A control strain containing the
      tet(Q) gene from Bacteroides thetaiotaomicron had a different electrophoresis
      pattern for AluI. This study indicated that subtypes of the tet(Q) gene in
      tetracycline-resistant gram-negative periodontal bacteria exist both within the
      same patient and within the same species.

PMID- 9028256
TI  - Effect of host responses on the pathogenicity of strains of Porphyromonas
      gingivalis.
AB  - Porphyromonas gingivalis is implicated in the etiology of periodontitis. Strains
      of P. gingivalis have been classified as invasive or noninvasive based on their
      ability to form abscesses in a mouse model. The purpose of this study was to
      investigate the ability of P. gingivalis strains to cause abscesses and
      periodontal bone loss in an experimental rat model and the effect of serum and
      salivary responses on the pathogenicity of these strains. Subcutaneous injection
      of animals with P. gingivalis 33277, A7A1-28, W50 or 381 resulted in abscesses in
      a higher percentage of mice than rats. P. gingivalis 33277 caused lesions at the
      site of injection, whereas strains A7A1-28 and W50 induced abscesses at distant
      sites in both mice and rats. Local lesions were seen in rats injected with strain
      381, whereas lesions formed distant from the site of injection in mice. When
      periodontal bone loss was assessed in the experimental rat model, animals
      challenged with 33277 had the highest amount of horizontal and vertical bone
      loss. Rats challenged with strain A7A1-28, W50 or 381 had some or no periodontal
      bone loss compared with controls. Assessment of antibody responses to P.
      gingivalis in these animals revealed that rats challenged with 33277 had lower
      levels of serum immunoglobulin G-(IgG) and especially salivary IgA antibody
      activity than A7A1-28-challenged rats. Serum IgG and in particular salivary IgA
      anti-P. gingivalis responses were seen in W50- and 381-challenged rats. These
      results indicate that the ability of P. gingivalis strains to cause abscesses
      does not relate directly to their periodontal pathogenicity as assessed by
      periodontal bone loss in the same animal model. The results further suggest the
      importance of salivary IgA antibody responses in protection against experimental
      periodontal bone loss after challenge with P. gingivalis.

PMID- 9028257
TI  - Lipopolysaccharide isolated from Porphyromonas gingivalis grown in hemin-limited
      chemostat conditions has a reduced capacity for human neutrophil priming.
AB  - One way prokaryotes respond to environmental stresses is by modifying selected
      outer membrane components. Iron, in the form of hemin, has been shown to be a
      significant regulator of Porphyromonas gingivalis growth and virulence and of the
      expression of outer membrane proteins and lipopoly saccharide. Since lipopoly
      saccharide has profound effects on host immune cells, this study compared the
      effect of hemin-restricted and hemin-normal P. gingivalis growth conditions on
      lipopolysaccharide priming of N-formylmethionyl-leucyl-phenylalanine-induced
      superoxide generation by human neutrophils. P. gingivalis was grown in a
      chemostat under normal (5 micrograms hemin/ml) and hemin-restricted (0.08
      microgram hemin/ml) conditions. Purified lipopolysaccharide from both P.
      gingivalis normal and hemin-limited environments increased N-formylmethionyl
      leucyl-phenylalanine-induced superoxide release by neutrophils in a dose
      dependent manner. Lipopolysaccharide isolated from the hemin-normal conditions
      was a significantly more potent neutrophil priming agent than the
      lipopolysaccharide isolated from hemin-restricted conditions. Addition of normal
      human serum enhanced the priming effect of both lipopolysaccharide preparations;
      this effect, however, was more evident with the hemin-normal lipopolysaccharide.
      Further, this enhancing effect of serum was partly reduced in the presence of
      antibodies raised against the serum lipopolysaccharide-binding protein. The
      differences in the biological activity of the two lipopolysaccharide preparations
      could be associated with structural differences detected by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis. These results indicate that
      hemin availability affects regulation of an aspect of P. gingivalis virulence,
      lipopolysaccharide-human neutrophils priming. The reduced capacity for neutrophil
      priming by hemin-restricted lipopolysaccharide appears to be related to
      lipopolysaccharide-neutrophil interactions and not to serum factors Targeting
      bacterial cell-surface components involved in hemin transport might be effective
      therapy for P. gingivalis-associated periodontal diseases.

PMID- 9028258
TI  - Laminin binding to a heat-modifiable outer membrane protein of Actinobacillus
      actinomycetemcomitans.
AB  - The interaction of Actinoabacillus actinomycetemcomitans with the basement
      membrane protein, laminin, was examined in a 125I-labeled protein-binding assay.
      The binding of laminin increased by lowering the pH. The ability to bind laminin
      was decreased in cells at the stationary phase of growth and by the presence of
      blood in the culture medium. Laminin binding to this bacterium was saturable, and
      the affinity constant was 4.6 nM. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis and Western blot (ligand blot) analysis of cell-envelope and
      outer membrane of A. actinomycetemcomitans displayed a 125I-laminin-reactive
      protein band with a molecular weight of 29 k. The laminin-binding protein was the
      previously described outer membrane protein A of A. actinomycetemcomitans. It was
      identified by its heat-modifiable property, detergent-solubility profile and
      reactivity with outer membrane protein A-specific polyclonal antiserum. At acidic
      pH, 25I laminin bound to several cell-envelope components of A.
      actinomycetemcomitans, but at neutral pH, laminin bound only to the heat
      modifiable protein. Despite the existence of the laminin-binding protein, cells
      grown in blood-containing media did not bind laminin. Several mammalian proteins
      interfered with laminin-bacterial interaction, including lactoferrin, which binds
      to the same bacterial protein that inhibited and displaced the laminin-bacterial
      interaction.

PMID- 9028259
TI  - Effect of oral bacteria on peripheral blood leukocyte interleukin-6 and soluble
      interleukin-6 receptor production.
AB  - To determine the effect of pathogenic oral bacteria on interleukin 6 (IL-6) and
      soluble IL-6 receptor production, we measured their release by human peripheral
      blood mononuclear cells in vitro. Unseparated peripheral blood mononuclear cells,
      peripheral blood lymphocytes (monocyte depleted), pure T cells, or monocytes were
      cultured with Actinobacillus actinomycetemcomitans, Capnocytophaga gingivalis,
      Capnocytophaga ochracea, Fusobacterium nucleatum or Porphyromonas gingivalis for
      24 h. Supernatants were tested for IL-6 and soluble IL-6 receptor by enzyme
      linked immunosorbent assay. Only monocytes and peripheral blood mononuclear cells
      responded with significant IL-6 release in the presence of all bacteria tested.
      However, peripheral blood lymphocytes were capable of producing IL-6 when
      activated by phytohemagglutinin or IL-2 followed by bacteria, though
      substantially less than cultures containing monocytes. No bacteria tested
      increased soluble IL-6 receptor release over spontaneous soluble IL-6 receptor
      release. We conclude that monocytes release IL-6 after contact with oral
      pathogens; however, soluble IL-6 receptor from T cells and monocytes is
      constitutively produced and may modulate IL-6 actions.

PMID- 9028260
TI  - Lymphocyte adhesive interactions with cultured parotid salivary gland epithelial
      cells from rats.
AB  - Cellular interactions control lymphocyte localization within salivary gland
      tissues and contribute to the immune defense of oral surfaces. We examined
      lymphocyte adherence to cultured parotid cells using an in vitro assay and found
      good correlation with previously reported binding to parotid gland frozen
      sections. Thoracic duct lymphocytes (TDL) bound to parotid cells in greater
      numbers than thymocytes (74 vs 11 cells/mm2). B cells showed preferential
      adherence compared to T cells (75% vs 28%). TDL binding was inhibited by sodium
      azide or cytochalasin B (60% and 80%, respectively). EDTA inhibition (63%) was
      restored by replacing calcium (9%) but not magnesium (65%). Binding was inhibited
      by fucoidin or phosphomannan (approximately 70%). Fibronectin peptides had no
      effect. Culture supernatants were inhibitory for TDL adherence (60%), suggesting
      that molecules involved in lymphocyte localization may be shed and that parotid
      cell cultures will be useful for ligand isolation and characterization.

PMID- 9028262
TI  - The inhibitory action of fatty acids on oral bacteria.
AB  - Saturated and unsaturated fatty acids and fatty acid derivatives were examined
      for their growth-inhibitory effects towards three selected oral bacteria:
      Porphyromonas gingivalis, Selenomonas artemidis, and Streptococcus sobrinus. Of
      the 45 compounds surveyed, only one, myristoleic acid, was inhibitory towards S.
      artemidis at a concentration < 100 micrograms/ml. cis-Hexadecenoic and cis
      octadecenoic acids were generally inhibitory towards P. gingivalis and S.
      sobrinus, but there was no correlation between the position of the double bond
      and the minimum inhibitory concentration. Supra-minimum inhibitory concentrations
      of palmitoleic acid did not promote leakage of intracellular materials from
      either P. gingivalis or S. sobrinus, nor was L-isoleucine uptake by S. sobrinus
      inhibited. Fatty acids and derivatives were also examined for prospective
      synergistic or antagonistic interactions with thymol vis-a-vis growth inhibition
      of the test strains. Lauric acid and myristic acid each behaved synergistically
      with thymol to inhibit the growth of at least one test strain, whereas cis-10
      heptadecenoic acid and thymol were noticeably antagonistic towards the growth of
      S. sobrinus.

PMID- 9028261
TI  - Identification of human antigenic epitopes in an alanine-rich repeating region
      using sera from hu-PBL-SCID mice immunized with a surface protein antigen of
      Streptococcus mutans.
AB  - A 190-kDa surface protein antigen (PAc) of Streptococcus mutans is considered to
      play an important role in dental caries. To identify antigenic epitopes of the
      PAc in humans, we immunized severe combined immunodeficient (SCID) mice with
      recombinant PAc that was transplanted with human peripheral blood mononuclear
      cells (PBMC). The reactivities of the sera from the immunized hu-PBL-SCID mice to
      the recombinant PAc and 24 19-mer synthetic peptides covering the alanine-rich
      repeating region (A-region) presented in the PAc molecule were then examined. The
      results showed that the immunized mice produced a significant recombinant PAc
      specific human antibody, and among 24 19-mer peptides, 6 19-mer peptides showed a
      strong reaction with the antibodies. In addition, 4 19-mer peptides containing
      human antigenic epitope in a donor were identified with enzyme-linked
      immunosorbent assay (ELISA) inhibition assays using the recombinant PAc protein.
      In this study, the SCID mouse was useful in identifying human antigenic epitopes.

PMID- 9028264
TI  - Winning at all costs.

PMID- 9028263
TI  - Development and evaluation of a selective and differential medium for the primary
      isolation of Peptostreptococcus micros.
AB  - Peptostreptococcus micros, an anaerobic gram-positive coccus, has been associated
      with periodontal and endodontic lesions, including those refractory to treatment,
      as well as many human polymicrobial infections in other body locations. A
      selective and differential medium for the primary isolation of P. micros was
      developed and evaluated. Columbia CNA agar, a selective medium for gram-positive
      cocci, was supplemented with glutathione and lead acetate (P. micros medium:
      PMM). P. micros has a characteristic of rapidly utilizing the reduced form of
      glutathione to form hydrogen sulfide, which reacts with lead acetate producing a
      black precipitate in the medium. When grown on PMM, P. micros can be easily
      identified by its typical colonial morphology and the presence of a black
      precipitate directly under the colony. PMM was compared for the growth of P.
      micros with phenylethyl alcohol agar (PEA) and Columbia base medium (CBM) with 80
      strains of P. micros and 30 strains of other gram-positive cocci. All P. micros
      isolates tested grew and showed the typical morphology of P. micros on PMM. Using
      colony counts on CBM as controls, there was an average 81.8% recovery in the
      number of P. micros colonies on PMM, in contrast to an average 6.1% recovery on
      PEA. Subgingival plaque and tongue samples from 12 adult periodontitis and 6
      early-onset periodontitis patients were cultured onto PMM for the isolation of P.
      micros. P. micros was isolated on PMM and identified biochemically and
      enzymatically from both adult periodontitis and early-onset periodontitis
      patients with higher percentages isolated from the diseased periodontal pockets
      of adult periodontitis patients; furthermore, this is the first isolation of P.
      micros from tongue samples taken from periodontally diseased patients. This
      medium in cultural studies will further our understanding and assist future
      investigations of P. micros involved in disease processes.

PMID- 9028265
TI  - The best way.

PMID- 9028266
TI  - Utilization of a resorbable collagen membrane in repairing gingival recession
      defects.
AB  - Predictable coverage of exposed root surfaces and the corresponding treatment of
      gingival recession defects remain important objectives of periodontal therapy. A
      variety of techniques have been developed during the past several decades to
      address this common clinical challenge. Traditional surgical approaches have been
      relatively successful in achieving root coverage. Attempts have been made
      recently to achieve root coverage with surgical techniques based on the
      principles of guided tissue regeneration, using resorbable and nonresorbable
      materials. The learning objective of this article is to present case
      documentations of root coverage, using a resorbable collagen barrier. The results
      achieved illustrate the potential of this material in the treatment of gingival
      recession. The biologic properties of collagen as a barrier material, the
      surgical approach, and the principles of case selection are reviewed.

PMID- 9028267
TI  - Implant site preparation with osteotomes: principles and clinical application.
AB  - The use of implant-supported restorations is a well-accepted and predictable
      treatment modality. Drilling has been the traditional method for cylindrical
      implant site preparation. This procedure, however, removes a considerable amount
      of bone. This article presents an alternative site preparation method--the use of
      osteotomes--which preserves, expands, and condenses alveolar bone. Indications,
      advantages, and the clinical procedure are presented, with extensive details on
      bone preservation, expansion, condensation, and sinus floor elevation. The
      learning objective of this article is to familiarize the reader with the
      principles of this alternative method and the clinical application of osteotomes.

PMID- 9028268
TI  - Small-segment symphysis graft: augmentation of the maxillary anterior ridge.
AB  - The loss of a tooth results in loss of alveolar bone, required for the placement
      and retention of implants. Bone can be replaced by various augmentation
      modalities, including a small-segment symphysis graft. The selection of the donor
      site, the preparation of the recipient and donor sites, the procedures of graft
      placement, and the closure of the donor site are presented and described. The
      corticotrabecular graft is obtained with a trephine drill from the mandibular
      symphysis and grafted to a recipient site that has been prepared with ridge
      expanding osteotomes. The graft is then mortised with a combination of an
      alloplast, freeze-dried demineralized bone, and autogenous bone harvested from
      the symphysis donor site. The learning objective of this article is to describe
      the procedures of a small-segment symphysis graft, using a clinical case to
      illustrate the text. After graft healing and lost bone regeneration, implants can
      be placed.

PMID- 9028269
TI  - Developing soft tissue contours for implant-supported restorations: a simplified
      method for enhanced aesthetics.
AB  - The success of a full coverage crown restoration, whether placed on a natural
      abutment or a dental implant, requires healthy and correctly contoured soft
      tissue "framing" for the restoration. Any compromise in soft tissue configuration
      may result in an aesthetic and functional failure of the final restoration.
      Traditionally, soft tissue grafts and other augmentation materials have been
      utilized to develop natural contours and appearance. The learning objective of
      this article is to present a simplified technique--the use of wide diameter
      prosthodontic components--for establishing the correct soft tissue profile. This
      technique enables the clinician to develop an anatomically correct implant
      supported restoration with an aesthetic final result.

PMID- 9028270
TI  - The enemy within.

PMID- 9028271
TI  - Predictable aesthetic reconstruction of fractured anterior teeth with composite
      resins: a case report.
AB  - Full-coverage rehabilitation is generally the treatment modality indicated for
      restoration of severely fractured anterior teeth. However, the advanced
      formulations of composite resins present improved physical properties, an
      expanded range of shade selection, and high sculptability, allowing predictable
      restoration of the anterior dentition and replication of the polychromatic
      characteristics of natural teeth. The learning objective of this article is to
      present the utilization of composite resin materials in the treatment of
      fractured maxillary anterior incisors, implementing the concepts of polychromatic
      characteristics, hue, translucency, opacity, chroma, value, strength, and
      polishability. Also presented are several practical clinical observations that
      will assist the practitioner in attaining predictable aesthetic results with
      composite resin material.

PMID- 9028272
TI  - Whatever it takes.

PMID- 9028273
TI  - Aesthetic guidelines for posterior composite restorations.
AB  - The development of composite resin materials that combine the required strength
      and wear resistance with the appropriate color palate which resembles natural
      dentition has enabled the clinician to successfully place composite restorative
      materials in the posterior region. Appropriate techniques have been developed for
      utilization of the new materials. This article reviews the selection of posterior
      composite materials, indications, and force factors. Preparation guidelines are
      presented, including a review of the criteria established by G.V. Black. The
      article also reviews the indications, preparation guidelines, bonding materials,
      composite placement techniques, and finishing protocols for posterior composite
      restorations. Three case presentations illustrate the clinical procedure. The
      learning objective of this article is to enhance the knowledge of materials
      currently available for posterior tooth-color restorations and their application
      techniques.

PMID- 9028274
TI  - Stratification of composite restorations: systematic and durable replication of
      natural aesthetics.
AB  - A thorough knowledge of the internal structure of natural dentition provides
      invaluable information for increasing the aesthetic potential in dental
      restorations. To achieve the optimal aesthetic results, this knowledge must be
      integrated in a systematic therapeutic procedure. The learning objective of this
      article is to guide the practitioner in clinical case analysis, evaluation, and
      the application of a personalized technique of stratification for each individual
      case in direct composite restorations. The article evaluates treatment
      demarcations, differences in composite stratification between anterior and
      posterior teeth, color selection, and the "sandwich technique." The treatment
      protocol section discusses the element of reference, which can be either an
      adjacent natural tooth or provisional restorations, permitting the diagnostic
      study of a more extensive case. The structure of the element of reference is
      analyzed as to the enamel, dentin, and incisal edge, and replicated. Since light
      penetration is different in the anterior and posterior dentition, the color
      stratification must differ accordingly. The "worn" tooth must be distinguished
      from the "unworn" tooth. In color selection, the luminosity and saturation of the
      teeth are evaluated first; tint is selected from the element of reference.

PMID- 9028275
TI  - All-ceramic fixed restorations: a preliminary clinical evaluation.
AB  - This article is a preliminary evaluation of a limited size clinical trial of all
      ceramic fixed restorations. The maxillary anterior region in each of eight
      patients was restored with single-unit and three-unit fixed restorations, using a
      particular all-ceramic system. Patient selection, laboratory procedures, clinical
      techniques, patient follow-up, and the interim clinical results of the
      restorations, are presented and evaluated. The learning objective of this article
      is to review and update the knowledge of all-ceramic restorative materials and
      clinical procedures. Two of the eight cases in the study are presented to
      illustrate the clinical results.

PMID- 9028277
TI  - The exam was a sham.

PMID- 9028276
TI  - Aesthetic solution for large maxillary anterior diastema and frenum attachment.
AB  - Resin-bonded porcelain veneer restorations can be used to correct unaesthetic
      diastemata caused by tooth position or discrepancies in the tooth size/arch
      development. The size of the diastema, size and proportion of the clinical
      crowns, tooth preparation, and dental occlusion require special attention; an
      excessive frenum attachment requires additional care and coordination of the
      treatment. This article describes the placement of six resin-bonded porcelain
      veneer restorations in a patient with a large diastema between the maxillary
      central incisors and associated frenum and soft tissue involvement. The learning
      objective of this article is to demonstrate the importance of pretreatment
      planning and problem solving in achieving predictable final restorations.

PMID- 9028278
TI  - Masking severely tetracycline-stained teeth with ceramic laminate veneers.
AB  - When the primary restorative objective is the reinstatement of vital natural
      tooth color, dark tetracycline-stained teeth still represent the ultimate
      challenge for ceramic laminate veneers. Masking severe stain with opaquing
      composite resins is a significant advancement; however, the procedure requires
      additional chairtime, is technique sensitive (to avoid excessive opacity), and
      involves removal of additional tooth structure. The learning objective of this
      article is to describe and compare two different methods for masking tetracycline
      stained teeth. The article illustrates the natural tooth color derived from
      ceramic laminate veneers when bonded to opaque composite resins in the maxillary
      arch, and compares it to a new ceramic veneer formulation in the mandibular arch,
      which masks the stain, eliminates the need for subopaquing with composite resins,
      and resembles the qualities of natural tooth color.

PMID- 9028279
TI  - Cervical contouring concepts: enhancing the dentogingival complex.
AB  - The importance of the mucogingival complex in any restorative procedure has long
      been recognized, and various surgical and nonsurgical procedures have been
      developed to restore the compromised gingiva to its original health. The learning
      objective of this article is to review nonsurgical restorative techniques to
      manipulate the soft tissue surrounding the cervical aspect of the restored tooth
      into a more favorable contour. The techniques presented are applicable to direct
      and indirect restorations. Six case reports are used to illustrate the various
      clinical procedures. The techniques include: Supragingival direct restorative
      techniques, such as recontouring intact dentition; and intracrevicular indirect
      techniques, such as recapturing the soft tissue of deficient crown restorations,
      re-engineering recessed injured tissue, re-creation of hyperplastic injured
      tissue, re-engineering hyperplastic recessed posttrauma tissue, and re
      engineering the periprosthetic envelope.

PMID- 9028281
TI  - Layering techniques and aesthetic anterior restorations: what's really new?

PMID- 9028280
TI  - Class V restorations utilizing a new compomer material: a case presentation.
AB  - Restorative materials used in the anterior cervical region should be able to
      restore the affected area in an aesthetic manner, require only a minimal amount
      of tooth structure removal, and provide protection from further cervical
      decalcification. The latest generation of restorative materials have combined the
      qualities of composite resins and glass-ionomers. Some of these materials
      incorporate resin components into glass-ionomer systems and are termed resin
      modified glass-ionomers; others add glass-ionomer particles to acidic
      polymerizable monomers in a resin matrix and are commonly called "compomers." The
      learning objective of this case report is to present a step-by-step clinical
      procedure for restoration of a Class V defect in the maxillary anterior region,
      using a recently introduced "compomer."

PMID- 9028282
TI  - Atypical trigeminal neuralgia.

PMID- 9028283
TI  - An effective technique for extended proximal contacts in composite resin
      restorations.
AB  - Obtaining a firm anatomic contact has been a difficult criteria in placing Class
      II posterior composite restorations. Various techniques have been developed and a
      number of products marketed to accomplish this task, but none have combined the
      necessary qualifications of ease, simplicity, and effectiveness for consistent
      and predictable results. To address this challenge, two innovative devices--a
      precontoured (biplanar concave) sectional matrix band and a light--focusing tip
      have been developed. Using a clinical case presentation, this article describes
      the application of these devices to obtain high quality proximal contacts, even
      in widely separated teeth. The learning objective of this article is to
      familiarize clinicians with this procedure. The technique is simple and
      universally applicable with a variety of posterior composite materials and
      placement methods.

PMID- 9028284
TI  - Strength, anatomic adaptation, and aesthetic of a new all-ceramic restorative.

PMID- 9028285
TI  - Trying to keep faith in humanity.

PMID- 9028286
TI  - Ridge augmentation using mandibular ramus bone grafts for the placement of dental
      implants: presentation of a technique.
AB  - Local bone grafts are a convenient source of autogenous bone in alveolar
      reconstruction. The mandibular ramus area provides primarily a cortical graft
      that is well-suited for veneer-grafting of ridge deficiencies prior to implant
      placement. The advantages of this method of augmentation include its intraoral
      access and low morbidity. Similar to bone harvested from the mandibular
      symphysis, these grafts require short healing periods, exhibit minimal
      resorption, and maintain their dense quality. Advantages of this donor site over
      the chin include minimal patient concern for altered facial contour, proximity to
      posterior mandible recipient sites, and decreased complaints of postoperative
      sensory disturbances and discomfort. However, the surgical access in some cases
      is limited, and there is a potential for damage to the mandibular neurovascular
      bundle. The learning objective of this article is to review and update the reader
      knowledge of alveolar ridge augmentation using mandibular grafts.

PMID- 9028287
TI  - Ovate pontics: the natural tooth replacement.

PMID- 9028288
TI  - Guided tissue regeneration/guided bone regeneration: a review of the barrier
      membranes.

PMID- 9028289
TI  - A single-step GTR treatment for gingival recession with a bioresorbable membrane:
      a case report.
AB  - Creating a single-step surgical treatment for coverage of gingival recession has
      long been the objective in the development of guided tissue regeneration. A
      single-step procedure would avoid the trauma of a second surgery and eliminate
      the limitations associated with soft tissue grafts and nonresorbable barriers. It
      would also ensure the predictable integration of the bioresorbable membrane in
      the periodontal tissue and the clinical repair of gingival recession. The
      learning objective of this article is to present the clinical application of a
      bioresorbable matrix along with the indications and advantages of the procedure.
      Three case reports are used to illustrate the clinical technique.

PMID- 9028290
TI  - Guided periodontal tissue regeneration (GPTR): an update.
AB  - Periodontal therapy has three primary objectives--elimination of etiologic
      factors, repair or regeneration of the lost attachment apparatus, and prevention
      of further periodontal breakdown. Significant progress has occurred in the area
      of surgical periodontal therapy during the last two decades. Periodontal
      regeneration has become a viable treatment option utilizing the principles of
      guided tissue regeneration. The learning objective of this article is to review
      the biologic rationale, the various barrier materials currently available, and
      the surgical techniques for guided periodontal tissue regeneration procedures
      using nonresorbable and resorbable barriers, with and without bone grafting
      materials.

PMID- 9028291
TI  - Pain management in dentistry: an introduction.

PMID- 9028292
TI  - Pain management in guided tissue regeneration.

PMID- 9028294
TI  - Paradigm shifts be damned.

PMID- 9028293
TI  - Clinical evaluation of an acellular dermal allograft for increasing the zone of
      attached gingiva.
AB  - Grafting with autogenous tissue or freeze-dried skin is the generally accepted
      method for increasing and/or restoring the width of attached gingiva. This
      article describes the periodontal use of an acellular dermal allograft previously
      available for treating burn patients. When used as a gingival graft, this new
      dermal allograft has major potential advantages over the previously available
      periodontal graft materials, including improved color and contour match,
      elimination of multiple surgeries, and unlimited availability. The technique and
      results of acellular dermal grafting are presented and discussed. The learning
      objective of this article is to describe the principles and the clinical
      procedure of this technique. Several cases are used to illustrate this technique.

PMID- 9028295
TI  - The exam was a sham.

PMID- 9028296
TI  - The aesthetic guidelines of the mucogingival complex for fixed prosthodontics.
AB  - Until the 1980s, aesthetic dentistry focused its attention primarily on the
      replication and improvement of tooth structure by developing modifications of
      porcelain-fused-to-metal crown restorations, incorporated in porcelain systems in
      combination with adhesive technology. The introduction of new, improved, or
      modified periodontal surgical techniques addresses nearly all mucogingival
      challenges, except for the loss of papillae. Therefore, it is of critical
      importance to develop and define aesthetic guidelines for treatment of the
      mucogingival complex. In these guidelines, the aesthetic analysis of a treatment
      is divided into an evaluation of the mucogingiva and that of the tooth structure.
      Correction of mucogingival discrepancies is a prerequisite for aesthetic success
      in dental treatment. The learning objective of this article is to review the
      mucogingival discrepancies and examine a variety of potential solutions.

PMID- 9028297
TI  - Reconstruction of function and aesthetics of the maxillary anterior region: a
      combined periodontal/orthodontic therapy.
AB  - Severe cases of periodontal disease often require periodontal surgery. Techniques
      have been developed attempting to minimize the postsurgical gingival recession
      and compromise of the interdental papillae. This article presents a case report
      in which soft tissue regenerative surgery was minimized through combined
      utilization of periodontal and orthodontic principles. The treatment plan
      included the control of periodontal inflammation, restoration of lost attachment
      apparatus, realignment of anterior dentition, and stabilization of occlusion. The
      anticipated loss of a maxillary central incisor was avoided. The learning
      objective of this article is to present the advantage of the interdisciplinary
      form of therapy in such challenging cases.

PMID- 9028298
TI  - Treatment of complex traumatic anterior dental injuries: a pediatric case report.
AB  - Traumatic injuries of permanent teeth in children present complex challenges.
      Growth and development influences, orthodontic considerations, and unknown
      endodontic and periodontal sequelae preclude immediate intervention with long
      term restorations. "Interim" solutions are required to return the patient to the
      normal appearance, function, and health of the dental/alveolar complex until
      maturation of the patient allows long-term treatment planning. This report
      outlines diagnosis and treatment of multiple injuries, sustained by the maxillary
      anterior teeth. Step-by-step clinical procedures and their rationale are
      described. The learning objective of this case report is to outline the
      principles for management of traumatic injuries of permanent anterior teeth in
      young patients and to demonstrate clinical techniques for splinting displaced
      teeth, bonding fractured teeth, providing endodontic therapy, and fabricating
      adhesively bonded resin composite restorations for interim full coverage of
      severely damaged permanent incisors in a child.

PMID- 9028299
TI  - Advanced adhesive restorations: the post-amalgam age.
AB  - Due to patient demand for biocompatible, safe, and tooth-colored restorations,
      the use of amalgam as a restorative material has been declining. Currently, the
      profession of operative dentistry is in a state of transition from the amalgam
      age to the post-amalgam age. The learning objective of this article is to discuss
      the current state of the art of tooth-colored restoratives--amalgam substitutes
      and amalgam alternatives--used either as direct or laboratory fabricated
      restorations nationally and internationally. Adhesive dentistry is discussed in
      detail, with tooth preparation as the key element. The challenges facing the
      clinician during the transition period include clinician education, restorative
      concepts and teaching competence, costs, prevention, and maintenance.

PMID- 9028300
TI  - Options: the key to satisfied patients.

PMID- 9028301
TI  - Optimizing form and function with the direct posterior composite resin: a case
      report.
AB  - The acceptance of mercury-containing restorative materials has declined, and the
      demand for amalgam substitutes has resulted in development of a variety of
      composite resins. Microhybrids are the newest generation of composite resins, and
      they incorporate particles of different sizes to maximize wear, polishability,
      and handling characteristics. The learning objective of this article is to
      present a technique to maximize form, function, and aesthetics in the placement
      of a posterior composite resin restoration. Shade selection, use of caries
      indicator, "total etch" technique, new generation bonding agent, and incremental
      resin placement are discussed. A step-by-step case presentation demonstrates that
      an appropriately placed direct posterior composite resin provides an excellent
      alternative to the traditional metal-colored restorations.

PMID- 9028302
TI  - Bone grafting: materials and modes of action.

PMID- 9028303
TI  - Pain management. Temporal tendonitis.

PMID- 9028304
TI  - Iron-chelating therapy and the treatment of thalassemia.
AB  - Iron-chelating therapy with deferoxamine in patients with thalassemia major has
      dramatically altered the prognosis of this previously fatal disease. The
      successes achieved with deferoxamine, as well as the limitations of this
      treatment, have stimulated the design of alternative strategies of iron-chelating
      therapy, including orally active iron chelators. The development of the most
      promising of these, deferiprone, has progressed rapidly over the last 5 years;
      data from several trials have provided direct and supportive evidence for its
      short-term efficacy. At the same time, the toxicity of this agent mandates a
      careful evaluation of the balance between risk and benefit of deferiprone in
      patients with thalassemia, in most of whom long-term deferoxamine is safe and
      efficacious therapy.

PMID- 9028305
TI  - Identification of the cDNA for human red blood cell-specific hexokinase isozyme.
AB  - A unique cDNA for hexokinase (HK) was identified from poly(A)+ RNA of human
      reticulocytes by anchored polymerase chain reaction. This appeared to represent
      the cDNA for the red blood cell (RBC)-specific HK isozyme (HKR) described in our
      previous study (Murakami et al: Blood 75:770, 1990). Its nucleotide sequence was
      identical to HKI cDNA except for the 5' extreme end. It lacked the first 62
      nucleotides of the HKI coding region: instead, it contained a unique sequence of
      60 nucleotides at the beginning of the coding sequence as well as another unique
      sequence upstream of the putative translation initiation site. It lacked the
      porin-binding domain which facilitates binding to the mitochondria, thus
      explaining the exclusive cytoplasmic localization of HKR. It was the major cDNA
      derived from reticulocytes, consistent with the observation that HKR activity is
      predominant in reticulocytes. Northern blot analysis showed that it was expressed
      in the reticulocytes and in the K562 erythroleukemic cell line, but not in a
      lymphocytic cell line. In the extract of K562 cells, HKR activity co-eluted with
      the HKR of human RBCs on a MonoQ column (Pharmacia, Piscataway, NJ)
      chromatography, using a salt gradient elution. The separate genetic control of
      the RBC-specific HK isozyme explains the clinical reports of two types of HK
      deficiency, one in which the HK activity was reduced exclusively in the RBC (HKR
      defect) and another with general decrease of HK activity in several tissues (HKI
      defect).

PMID- 9028306
TI  - A novel specific immunoassay for plasma two-chain factor VIIa: investigation of
      FVIIa levels in normal individuals and in patients with acute coronary syndromes.
AB  - We report the development of an enzyme-linked immunosorbent assay (ELISA) that is
      specific for factor VIIa (FVIIa). This assay uses a neoantigen specific capture
      antibody directed to the amino acid peptide sequence N terminal to the FVII
      cleavage activation site. The antibody exhibits approximately 3,000-fold greater
      reactivity to FVIIa than FVII on a molar basis. Experiments using plasma with
      added (exogenous) human FVIIa gave quantitative recovery in the ELISA over a
      range of 0.20 to 3.2 ng/mL of FVIIa. The intra- and inter-assay coefficient of
      variation (CVs) of the ELISA are 4.5% and 9.8%, respectively. The ELISA shows
      excellent correlation (r = .99) with a functional assay (using recombinant
      soluble tissue factor) in detecting FVIIa added to plasma over the range 0.05 to
      18.0 ng/mL. However, a major discrepancy exists between the two assays when
      normal endogenous plasma concentrations of FVIIa are measured. Using normal
      plasma (n = 14) the functional assay reported 3.10 +/- 0.30 ng/mL (mean +/- SE)
      whereas only 0.025 +/- 0.010 ng/mL was detected in the same samples by the
      immunoassay. Patients (n = 43) presenting with acute coronary syndromes
      (myocardial infarction and unstable angina) exhibited elevations (P < .05) in
      immunologically detected FVIIa, 0.093 +/- 0.013 ng/mL (mean +/- SE) compared to
      patient controls (n = 20) contemporaneously admitted with noncardiac chest pain,
      0.048 +/- 0.007 ng/mL (mean +/- SE). These elevations in the acute coronary
      syndromes were accompanied by increased (P < .05) and correlating prothrombin
      fragment F1 + 2 levels (Spearman correlation coefficient rs = .4, P < .01),
      demonstrating that thrombin generation is certainly associated with, and may even
      be caused by, extrinsic pathway activation.

PMID- 9028307
TI  - Development of antibodies to fetal calf serum with arthus-like reactions in human
      immunodeficiency virus-infected patients given syngeneic lymphocyte infusions.
AB  - In an attempt to restore immune competence to 12 human immunodeficiency virus-1
      (HIV-1)-infected patients, lymphocytes from their HIV-1-uninfected identical twin
      siblings were cultured in medium supplemented with 5% fetal calf serum (FCS),
      anti-CD3 antibody, and interleukin-2 (100 IU/mL) for 10 days and then infused
      into the patients. After multiple infusions, at 6- to 8-week intervals, half of
      the patients developed arthus-like reactions within 4 to 12 hours of infusion
      consisting of fever > 39 degrees C, hypotension, rigors, arthralgias, myalgias,
      headache, and/or malaise. Preinfusion and postinfusion serum samples were
      evaluated for the presence of antibodies to FCS using double immunodiffusion. All
      preinfusion serum samples were negative by this method while 8 of the 12 patients
      developed antibodies to a single component of FCS after two or more infusions of
      lymphocytes cultured in FCS-supplemented medium. Prick skin testing to
      standardized beef extract was negative in all patients. There was a correlation
      between initial CD4 level and the development of antibodies to FCS (median
      initial CD4 count in FCS antibody positive patients = 362.0/microL v median
      initial CD4 count of nonresponders = 135.0/microL). There was no correlation with
      response to recall antigens in delayed-type hypersensitivity testing. We conclude
      that selected patients were sensitized to a single component of FCS carried on
      donor lymphocytes, despite thorough washing of the cells before infusion. The
      development of antibodies to FCS indicates that immune complex formation could
      have occurred after the cell infusions, resulting in the arthus-like reactions.
      These observations suggest that the therapeutic use of human lymphocytes cultured
      in FCS may expose the recipient to immunogenic substances with possible clinical
      sequelae.

PMID- 9028308
TI  - Granulocyte-colony stimulating factor (filgrastim) accelerates granulocyte
      recovery after intensive postremission chemotherapy for acute myeloid leukemia
      with aziridinyl benzoquinone and mitoxantrone: Cancer and Leukemia Group B study
      9022.
AB  - This study evaluated the effect of filgrastim (granulocyte colony-stimulating
      factor [G-CSF]) on the duration of granulocytopenia and thrombocytopenia after
      intensive consolidation therapy with diaziquone (AZO) and mitroxantrone for
      patients less than 60 years of age with acute myeloid leukemia (AML) in complete
      remission. Patients less than 60 years of age with AML who achieved complete
      remission (CR) with daunorubicin and cytarabine induction therapy, were scheduled
      to receive three sequential courses of high-dose cytarabine,
      cyclophosphamide/etoposide, AZQ, and mitroxantrone in a pilot study to determine
      their tolerance of these three sequential consolidation regimens. The initial
      patients treated with AZQ and mitroxantrone experienced prolonged bone marrow
      suppression and, therefore, subsequent cohorts were treated with G-CSF, 5
      micrograms/kg, beginning the day after completion of the third cycle of
      chemotherapy. There was a marked decrease in the duration of granulocytopenia
      less than 500/microL in two groups of patients receiving two different dose
      levels of AZQ and the same dose of mitoxantrone compared with patients not
      receiving the G-CSF. There was also a decrease in the need for hospitalization,
      as well as the duration of hospitalization. There was a trend towards shortening
      of the duration of thromobocytopenia, as well. The duration of complete remission
      and overall survival was similar in patients who received or did not receive G
      CSF. G-CSF markedly shortened the duration of granulocytopenia in patients with
      AML receiving intensive postremission consolidation with AZQ and mitoxantrone.
      There was no adverse effect on CR duration or survival.

PMID- 9028309
TI  - Superiority of tandem autologous transplantation over standard therapy for
      previously untreated multiple myeloma.
AB  - Virtually no progress has been made during more than 2 decades of clinical trials
      for multiple myeloma (MM) involving standard therapy (ST). Recent studies suggest
      that dose intensification requiring hematopoietic stem cell support results in
      higher complete response (CR) rates and extended disease control. "Total Therapy"
      (TT) consisting of noncross-resistant induction regimens, followed by a double
      autotransplant (AT) procedure, was administered to 123 untreated patients with
      symptomatic MM. Upon hematologic recovery, interferon (IFN) maintenance (3
      million units [MU]/m2 subcutaneously thrice weekly) was given until disease
      recurrence/progression. Results were compared with the outcome of untreated
      patients receiving ST according to Southwest Oncology Group (SWOG) trials. One
      hundred sixteen pair mates were selected from both TT and among 1,123 patients to
      match for the major prognostic features. TT induced CR in 40% of all 123 patients
      (intent-to-treat). By 12 months, 7% had died, including 4% from treatment-related
      complications. With a median follow-up of 31 months, median durations of event
      free survival (EFS) and overall survival (OS) are 49 and 62+ months,
      respectively. Abnormalities of chromosomes 11q and 13 were associated with
      inferior outcome, whereas CR within 6 months after induction was a favorable
      prognostic feature for both EFS and OS. In comparison to ST, TT induced higher PR
      rates (85% v 52%, P < .0001) (CR rates not available on SWOG trials) and extended
      EFS (49 v 22 months, P = .0001) and OS (62+ v 48 months, P = .01). Compared to
      ST, dose intensification with double AT markedly augments tumor cytoreduction,
      effecting not only higher CR rates but also significantly extending EFS and OS in
      previously untreated patients with MM.

PMID- 9028310
TI  - Frequency and severity of central nervous system lesions in hemophagocytic
      lymphohistiocytosis.
AB  - We have retrospectively assessed the neurological manifestations in 34 patients
      with hemophagocytic lymphohistiocytosis (HLH) in a single center. Clinical,
      radiological, and cerebrospinal fluid (CSF) cytology data were analyzed according
      to treatment modalities. Twenty-five patients (73%) had evidence of central
      nervous system (CNS) disease at time of diagnosis, stressing the frequency of CNS
      involvement early in the time course of HLH. Four additional patients who did not
      have initial CNS disease, who did not die early from HLH complications, and who
      were not transplanted, also developed a specific CNS disease. Therefore, all
      surviving and nontransplanted patients had CNS involvement. Initially, CNS
      manifestations consisted of isolated lymphocytic meningitis in 20 patients and
      meningitis with clinical and radiological neurological symptoms in nine patients.
      For these nine patients, neurological symptoms consisted of seizures, coma, brain
      stem symptoms, or ataxia. The outcome of patients treated by systemic and
      intrathecal chemotherapy and/or immunosuppression exclusively (n = 16) was poor,
      as all died following occurrence of multiple relapses or CNS disease progression
      in most cases. Bone marrow transplantation (BMT) from either an HLA identical
      sibling (n = 6) or haplo identical parent (n = 3) was performed in nine patients,
      once first remission of CNS and systemic disease was achieved. Seven are long
      term survivors including three who received an HLA partially identical marrow.
      All seven are off treatment with normal neurological function and cognitive
      development. In four other patients, BMT performed following CNS relapses was
      unsuccessful. Given the frequency and the poor outcome of CNS disease in HLH, BMT
      appears, therefore, to be the only available treatment procedure that is capable
      of preventing HLH CNS disease progression and that can result in cure when
      performed early enough after remission induction.

PMID- 9028311
TI  - High-dose therapy and autologous hematopoietic progenitor cell transplantation
      for recurrent or refractory Hodgkin's disease: analysis of the Stanford
      University results and prognostic indices.
AB  - One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD)
      received high-dose therapy followed by autologous hematopoietic progenitor cell
      transplantation. Three preparatory regimens, selected on the basis of prior
      therapy and pulmonary status, were employed. Twenty-six patients without a
      history of prior chest or pelvic irradiation were treated with fractionated total
      body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg.
      Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A
      group of 19 patients with a limited diffusing capacity or history of pneumonitis
      received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and
      Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35
      (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years
      actuarial survival was 52%, event-free survival was 48% and freedom from
      progression (FFP) was 62%. No significant differences were seen in survival data
      with the three preparatory regimens. Six patients died within 100 days of
      transplantation and 5 died at a later date of transplant-related complications.
      Secondary malignancies have developed in 6 patients, including
      myelodysplasia/leukemia in four patients and solid tumors in two patients.
      Regression analysis identified systemic symptoms at relapse, disseminated
      pulmonary or bone marrow disease at relapse and more than minimal disease at the
      time of transplantation as significant prognostic factors for overall and event
      free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at
      4 years compared with 41% for patients with one or more unfavorable prognostic
      factors (P = .0001). Our results confirm the efficacy of high-dose therapy and
      autografting in recurrent or refractory HD. Although longer follow-up is
      necessary to address ultimate cure rates and toxicity, our data indicate that a
      desire to reduce late effects should drive future research efforts in favorable
      patients whereas new initiatives are needed for those with less favorable
      prognoses.

PMID- 9028312
TI  - Comparison between conventional salvage therapy and high-dose therapy with
      autografting for recurrent or refractory Hodgkin's disease.
AB  - Sixty patients with Hodgkin's disease, refractory to or at first recurrence after
      chemotherapy, received cytoreductive therapy followed by high-dose etoposide,
      cyclophosphamide and either total body irradiation or carmustine and autografting
      (median follow-up, 3.6 years; range, 1.1 to 7.5 years). A matched conventional
      salvage group of 103 patients was selected from patients treated at Stanford
      University Medical Center between January 1976 and January 1989 (median follow
      up, 10.3 years; range, 3.0 to 15.7 years). Overall survival (OS), event-free
      survival (EFS), and freedom from progression (FFP) at 4 years follow-up favored
      patients who received high-dose therapy compared with conventional salvage
      treatment (OS: 54% v 47%, P = .25; EFS: 53% v 27%, P < .01; FFP: 62% v 32%, P <
      .01). In Cox regression analysis, response to cytoreductive or salvage therapy
      and B symptoms at relapse were the most important predictors of OS. The use of
      high-dose therapy at relapse, a longer duration of remission, and favorable
      response to cytoreductive or salvage therapy were most predictive of superior FFP
      and EFS. These data from a single institution comparing conventional and high
      dose therapy in matched patients demonstrate an advantage for high-dose therapy
      and autografting in the sustained control of Hodgkin's disease. As with primary
      therapy, it is difficult to demonstrate a statistically significant survival
      advantage, despite an apparently superior cure rate. However, patients failing
      induction therapy or relapsing within 1 year benefited significantly from high
      dose therapy by all outcome measures (OS, EFS, FFP). As the transplant-related
      mortality rates decline in Hodgkin's disease, it is predicted that cure rates and
      late effects will become ultimate determinants of the success of high-dose
      therapy and autografting.

PMID- 9028313
TI  - A single injection of pegylated murine megakaryocyte growth and development
      factor (MGDF) into mice is sufficient to produce a profound stimulation of
      megakaryocyte frequency, size, and ploidization.
AB  - Despite numerous studies investigating the action of c-mpl ligand, no reports
      have defined the in vivo changes in megakaryocytopoiesis in response to a single
      injection of this cytokine. Here we compare the kinetics of the
      megakaryocytopoietic response in C57BI/6J mice administered 25 micrograms/ kg or
      250 micrograms/kg of pegylated (PEG) murine megakaryocyte growth and development
      factor (MGDF) as a single intravenous injection. Megakaryocytes of mice treated
      with MGDF had normal ultrastructure, showing a typical distribution of the
      demarcation membrane system, alpha-granules, and other cytoplasmic organelles.
      Megakaryocyte ploidy, size, and frequency were markedly increased with both MGDF
      doses. Megakaryocyte ploidy was maximally increased from a modal value of 16N to
      64N on day 3, with both doses of MGDF. Similarly, a comparable increase in
      megakaryocyte size occurred in the two MGDF groups. Increased megakaryocyte size
      was coupled to the increase in megakaryocyte ploidy, and no evidence for
      independent regulation of megakaryocyte size within individual ploidy classes was
      apparent. In contrast to megakaryocyte ploidy and size, the increase in
      megakaryocyte frequency was markedly different with the two doses of MGDF. The
      proportion of 2N and 4N cells was increased from a baseline of 0.035% to 0.430%
      by day 4 in mice treated with the higher dose of MGDF, but only to 0.175% in mice
      administered 25 micrograms/kg of MGDF. The marked increase in the pool of these
      immature megakaryocytes translated to a sustained elevation in the frequency of
      polyploid megakaryocytes (8N cells and greater). In contrast to the sustained
      increase in the frequency of polyploid cells, the level of polyploidization was
      downregulated on days 6 to 10, but normalized by day 14. We conclude that a
      single injection of MGDF is able to expand the megakaryocytic pool in a dose
      dependent manner, which, with subsequent maturation, should lead to an increased
      rate of platelet production.

PMID- 9028314
TI  - Population size and radiosensitivity of murine hematopoietic endogenous long-term
      repopulating cells.
AB  - A new assay is described that measures the numbers (n) of endogenous long-term
      repopulating cells (eLTRC) surviving sublethal irradiation. The assay is based on
      analysis of variances of Pgk-1 phenotypes within groups of sublethally irradiated
      Pgk-1(a/b) mice. When ln n is plotted as a function of dose, the radiosensitivity
      (D0) is the negative reciprocal of the slope and the gamma-intercept is N or
      total numbers of eLTRC per mouse. The assay is unique in that N is an absolute
      value not requiring correction for seeding efficiency, or f. From two independent
      estimates, total numbers of eLTRC were determined to be 8,700 or 11,900 cells per
      mouse and D0 was found to be 0.82 or 0.83 Gy. If eLTRC are, in fact, the long
      term repopulating cells (LTRC) defined by classical transfer assay, then LTRC can
      home to the marrow with nearly unit efficiency, only one to two LTRC are required
      for a mouse to survive a radiation LD50/30, and LTRC possess nearly unlimited
      self-renewal potential.

PMID- 9028315
TI  - Roles of the N and C terminal domains of the interleukin-3 receptor alpha chain
      in receptor function.
AB  - The interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and
      IL-5 receptor alpha chains are each composed of three extracellular domains, a
      transmembrane domain and a short intracellular region. Domains 2 and 3 constitute
      the cytokine receptor module (CRM), typical of the cytokine receptor superfamily;
      however, the function of the N-terminal domain is not known. We have investigated
      the functions of the N-terminal and C-terminal domains of the IL-3 receptor (IL
      3R) alpha chain. We find that cells transfected with the receptor beta chain (h
      beta c) and a truncated IL-3R alpha that is devoid of the intracellular region
      fail to proliferate or to activate STAT5 in response to human IL-3, despite
      binding the IL-3 with affinity indistinguishable from that of full-length
      receptor. In addition, IL-3-induced phosphorylation of h beta c was not detected.
      Thus, the IL-3R alpha intracellular region does not contribute detectably to
      stabilization of the receptor/ligand complex, but is essential for signal
      propagation. In contrast, a truncated IL-3R alpha with the N-terminal domain
      deleted interacts functionally with the beta chain; mouse cells transfected with
      these receptor chains proliferate in response to human IL-3 and STAT5
      transcription factor is activated. High- and low-affinity binding sites are
      retained, although the affinity for IL-3 is decreased 15-fold, indicating a
      significant role for the N-terminal domain in IL-3 binding.

PMID- 9028316
TI  - Role of bcl-2 in the development of lymphoid cells from the hematopoietic stem
      cell.
AB  - To investigate the role of bcl-2 in lymphohematopoiesis, a long-term bone marrow
      reconstitution system was established. Transplantation of 1,000 c-Kit+ Sca-1+ and
      lineage markers negative cells from bcl-2-l-mouse bone marrow resulted in long
      term reconstitution of nonlymphoid cells. However, T cells were totally absent
      and B-lymphocyte development was severely impaired at a very early stage of
      differentiation in the chimeric mouse. On the other hand, transplantation of day
      14 fetal liver cells from bcl-2-l-mice resulted in generation of both T and B
      cells in the recipient, albeit transiently. These data suggest that bcl-2 plays a
      critical role in the development of lymphoid progenitor cells from the
      hematopoietic stem cell (HSC), but is not essential for the development of
      nonlymphoid cells and the self-renewal of HSC. In addition, lymphopoiesis from
      fetal liver HSC appears to be less dependent on bcl-2 than adult bone marrow HSC.

PMID- 9028317
TI  - Activation of JAK2 in human vascular endothelial cells by granulocyte-macrophage
      colony-stimulating factor.
AB  - Besides the regulation of hematopoiesis, granulocyte-macrophage colony
      stimulating factor (GM-CSF)induces the expression of a functional program in
      endothelial cells (ECs) related to angiogenesis and to their survival in the bone
      marrow microenvironment. ECs express specific GM-CSF high-affinity binding sites,
      which mediate the proliferative and migratory response. We now report that ECs
      express the alpha and beta subunits of GM-CSF receptor (GM-CSFR), and that GM-CSF
      is able to activate the Janus kinase (JAK)2, a member of the cytosolic tyrosine
      kinase family, which is known to mediate signals of several non-tyrosine kinase
      receptors. JAK2 tyrosine phosphorylation, as well as activation of its catalytic
      activity, is induced by subnanomolar concentrations of GM-CSF and occurs within 3
      minutes of stimulation and persists at least for 10 minutes. The effect is
      specific as inferred by the lack of effect of heat-inactivated GM-CSF or
      neutralized by specific antibodies and by the finding that interleukin-5, which
      utilizes a specific alpha chain and the same beta chain of GM-CSFR, does not
      phosphorylate JAK2. Furthermore, we show that the amount of JAK2 physically
      associated with GM-CSFR beta chain is increased after GM-CSF stimulation and that
      GM-CSF triggers both beta chain and JAK2 tyrosine phosphorylation. Taken
      together, these results suggest that biologic activities of GM-CSF in vascular
      endothelium may, in part, be elicited by GM-CSFR-mediated JAK2 activation.

PMID- 9028318
TI  - Induction of fibrinogen biosynthesis and secretion from cultured pulmonary
      epithelial cells.
AB  - Although the liver is the primary site of fibrinogen (FBG) synthesis, epithelial
      cells from diverse tissues have been shown to express one or more of the FBG A
      alpha, B beta, and gamma chain genes. In contrast, marrow megakaryocytes, which
      store FBG in the alpha-granules, are thought not to express the FBG genes. Our
      earlier studies have shown that epithelial cells in a variety of extrahepatic
      tissues express the gamma chain gene ubiquitously, while the mRNAs for the A
      alpha and B beta chain genes are essentially undetectable. During systemic
      inflammation, the liver secretes increased levels of FBG into the circulation,
      and lung epithelium responds to local inflammation during pulmonary infection by
      increased transcription of the gamma-FBG gene. Therefore, to determine whether
      extrahepatic epithelial cells express the A alpha, B beta, and gamma chain genes
      in response to proinflammatory mediators, cultured lung epithelial cells were
      treated with interleukin-6 (IL-6) and dexamethasone (DEX). Northern blot analysis
      demonstrated that the levels of gamma-FBG mRNA in cultured lung (A549) and liver
      (HepG2) epithelial cells increased 2- to 10-fold in response to treatment.
      Reverse-transcriptase-polymerase chain reaction amplification demonstrated
      increased accumulation of steady state levels of FBG A alpha, B beta, and gamma
      chain mRNAs in lung epithelial cells after treatment. The basal level of lung
      cell gamma-FBG gene transcription was not accompanied by appreciable levels of A
      alpha and B beta chain gene transcription; however, nuclear run-on analysis
      suggested that the increase in lung cell FBG mRNAs in response to DEX +/- IL-6
      was due to new transcription. Furthermore, stimulation of lung epithelial cells
      with IL-6 + DEX resulted in maximal secretion of intact FBG (340 kD) composed of
      the characteristic A alpha, B beta, and gamma chain polypeptides. The data
      suggest that basal expression of the gamma-FBG gene in extrahepatic tissue occurs
      ubiquitously in the absence of detectable levels of A alpha- and B beta-FBG gene
      expression, which are then upregulated on induction of an inflammatory response.
      This would result in local synthesis and secretion of FBG in the injured tissue,
      supporting the hypothesis that production of FBG by extrahepatic epithelial cells
      in response to inflammation plays a role in wound repair.

PMID- 9028319
TI  - Thrombopoietin enhances the alpha IIb beta 3-dependent adhesion of megakaryocytic
      cells to fibrinogen or fibronectin through PI 3 kinase.
AB  - The effect of thrombopoietin (TPO) on the functional activity of surface alpha
      IIb beta 3 (GPIIbIIIa) was investigated in both primary human megakaryocytic
      cells, derived from peripheral blood CD34+ cells, and HEL hematopoietic cell
      line. TPO (100 ng/mL) induced a sixfold to ninefold enhancement of adhesion of
      both primary megakaryocytic and HEL cells to plates coated with either fibrinogen
      or fibronectin and a parallel increase of immunoreactivity to the PAC1 monoclonal
      antibody (MoAb) and fluorescein isothiocyanate-fibrinogen, both of which
      recognize an activated state of alpha IIb beta 3. The enhanced adhesion to
      fibrinogen or fibronectin was mediated by the Arg-Gly-Asp (RGD) recognition
      sequence of alpha IIb beta 3, as it was abolished by pretreatment of cells with
      saturating concentrations of RGDS peptide. A MoAb specific for the alpha IIb beta
      subunit of alpha IIb beta 3 also inhibited cell attachment to fibrinogen or
      fibronectin, while MoAb to anti-alpha v beta 3 or anti-alpha 5 integrins were
      completely ineffective, clearly indicating that alpha IIb beta 3 participates in
      this association. A role for PI 3 kinase (PI 3-K) in the TPO-mediated increase in
      alpha IIb beta 3 function in megakaryocytic cells was suggested by the ability of
      the PI 3-K inhibitor wortmannin (100 nmol/L) and antisense oligonucleotides
      directed against the p85 regulatory subunit of PI 3-K to completely block the TPO
      induced increase in alpha IIb beta 3 integrin activity upon TPO stimulation. The
      modulation of adhesiveness to extracellular matrix proteins containing the RGD
      motif mediated by TPO likely plays a physiologic role in megakaryocytopoiesis, as
      pretreatment of CD34+ cells with RGDS or anti-alpha IIb MoAb significantly
      reduced the number of megakaryocytic colonies obtained in a fibrinclot semisolid
      assay.

PMID- 9028320
TI  - P-selectin glycoprotein ligand-1 is essential for adhesion to P-selectin but not
      E-selectin in stably transfected hematopoietic cell lines.
AB  - P-selectin (CD62P) is a member of the selectin family of adhesion molecules
      involved in the regulation of leukocyte traffic. P-selectin glycoprotein ligand-1
      (PSGL-1) is a mucin-like molecule that is thought to be a primary ligand for P
      selectin. The interaction of P-selectin with PSGL-1 results in leukocyte rolling
      and recruitment of leukocytes to sites of inflammation and tissue injury.
      However, expression of PSGL-1 protein alone is insufficient for binding to P
      selectin. Several posttranslational modifications of PSGL-1, including
      sialylation, sulfation, and fucosylation by alpha 1,3-fucosyltransferase(s)
      (FucT), are required for functional interaction with P-selectin. Recently,
      several groups have reported that PSGL-1 might also serve as a ligand for E
      selectin. Differential posttranslational modifications of PSGL-1 may determine
      whether it can interact with either P- or E-selectin or both. To determine
      whether PSGL-1 is essential for adhesion to P- or E-selectin, we have constructed
      and analyzed a panel of stably transfected K562 cells. K562 cells express FucT-IV
      but not FucT-VII or PSGL-1, and do not bind to either E- or P-selectin. K562
      cells transfected with PSGL-1 cDNA also did not bind to either P- or E-selectin.
      Binding to P-selectin occurred only when K562 cells were cotransfected with both
      FucT-VII and PSGL-1. In contrast, expression of FucT-VII alone was sufficient for
      E-selectin binding. These data demonstrate that expression of PSGL-1 is not
      required for adhesion of a stably transfected hematopoietic cell line to E
      selectin, and suggest that FucT-IV alone cannot properly modify PSGL-1, expressed
      in transfected K562 cells, to bind P-selectin.

PMID- 9028321
TI  - Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative
      syndrome: a molecular and immunological analysis.
AB  - Programmed cell death (or apoptosis) is a physiological process essential to the
      normal development and homeostatic maintenance of the immune system. The Fas/Apo
      1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated
      by lymphoproliferation in MRL-lpr/lpr mice and by the recently described
      autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due
      to mutations in the Fas gene. We describe a novel family with ALPS in which three
      affected siblings carry two distinct missense mutations on both the Fas gene
      alleles and show lack of Fas-induced apoptosis. The children share common
      clinical features including splenomegaly and lymphadenopathy, but only one
      developed severe autoimmune manifestations. In all three siblings, we
      demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T
      cells; moreover, a chronic lymphocyte activation was found, as demonstrated by
      the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by
      the presence of high levels of serum activation markers such as soluble
      interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30).

PMID- 9028322
TI  - Cytokine-induced apoptosis of human natural killer cells identifies a novel
      mechanism to regulate the innate immune response.
AB  - Interferon-gamma (IFN-gamma) is critical for an effective innate immune response
      against infection. A combination of interleukins (ILs) derived from activated T
      cells (IL-2) and monocytes (IL-12), or monocytes alone (IL-15 and IL-12), induces
      optimal production of IFN-gamma from natural killer (NK) cells. The mechanism by
      which human NK cells downregulate their production of IFN-gamma is unknown. Here
      we show that the same cytokines that induce human NK cell IFN-gamma production
      subsequently induce apoptosis of the NK cells. Fas, bcl-2, or bax do not appear
      to be involved in this process. The mechanism of cytokine-induced apoptosis of
      human NK cells appears to involve NK cell production of tumor necrosis factor
      alpha (TNF-alpha). Neutralization of TNF-alpha or inhibition of TNF-alpha binding
      to the p80 TNF-alpha receptor partially inhibited apoptosis. Transforming growth
      factor-beta, which inhibits cytokine-induced NK cell production of IFN-gamma and
      TNF-alpha, also decreased cytokine-induced NK cell apoptosis. Costimulation of a
      CD3-CD56+ NK leukemia cell line with IL-2 and IL-12 or IL-15 and IL-12 induced
      apoptosis in vitro, which increased when combined with a chemotherapeutic agent.
      In summary, costimulation of human NK cells via the IL-2 receptor and the IL-12
      receptor induces significant IFN-gamma production, followed by NK cell apoptosis
      and a decline in IFN-gamma production. Hence, cytokines that activate this innate
      immune response may also serve to limit it via apoptosis. This novel observation
      may have implications for the regulation of the innate immune response during
      infection, the toxicity of combination cytokine therapy, and the treatment of NK
      cell leukemia.

PMID- 9028323
TI  - Maintenance of human germinal center B cells in vitro.
AB  - The ability to maintain germinal center (GC) B cells in culture should facilitate
      studies on the molecular and cellular events which accompany affinity maturation
      and the generation of memory in T-dependent responses. We have investigated the
      ability of cytokines to maintain human tonsillar GC B cells (IgD-/CD39
      /CD38+/CD77+) in the "CD40 culture system". In the absence of added cytokines,
      CD40 monoclonal antibody held on CD32-transfected L cells effectively sustained
      DNA synthesis in GC B cells for a maximum 3 to 4 days. Of the following cytokines
      (interleukin-1 beta [IL-1 beta], IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, and stem
      cell factor), only IL-2 and IL-4 provided a significant enhancement to DNA
      synthesis in the CD40 culture system; this was modest and short-term. Following a
      study on the cooperative activity between pairs of cytokines, triple combinations
      were identified that could maintain high levels of GC B-cell stimulation for at
      least 10 days. IL-10 was a common component of these synergistic cytokine
      cocktails, which were IL-10 + IL-4 + IL-7; IL-10 + IL-3 + IL-7; IL-10 + IL-1 beta
      + IL-2; IL-10 + IL-1 beta + IL-3, and IL-10 + IL-3 + IL-6. Culture of GC B cells
      with these cytokine combinations resulted in a net increase in viable cell
      numbers of 50% to 100% whereas total cell numbers increased up to fourfold. Cells
      recovered from these cultures retained a GC B-cell phenotype with a significant
      proportion being CD38+/CD44-, features characteristic of centroblasts. Studies
      with metabolically inactive CD32-L cells supported a role for stromal cell
      derived soluble factors in maintaining GC B cells in vitro.

PMID- 9028324
TI  - Expression of interleukin-7 receptor by lineage-negative human bone marrow
      progenitors with enhanced lymphoid proliferative potential and B-lineage
      differentiation capacity.
AB  - Relatively little is known about the relationship of lymphoid-associated gene
      expression to the proliferation and differentiation potential of early human bone
      marrow lymphoid progenitors. Surface expression of interleukin-7 (IL-7) receptor
      alpha (IL-7R alpha), a component of the high-affinity receptor for the lymphoid
      precursor growth factor IL-7, defined a CD34+ progenitor subset lacking the CD19+
      pro-B phenotype but demonstrating markedly enhanced lymphoid clonogenic capacity
      and the ability to differentiate into pro-B cells in short-term culture. These
      progenitors expressed mRNA for the lymphoid-associated genes Ig beta, RAG-1, and
      PAX-5, and were uniformly TdT-positive (TdT+). In contrast, IL-7R alpha-/CD19-/
      CD34+ progenitors had a 50-fold reduced lymphoid clonogenic capacity and did not
      differentiate into pro-B cells in short-term culture. Expression of TdT and the
      lymphoid-associated genes Ig beta and RAG-1, but not PAX-5, was detected in this
      fraction, although at lower levels than in the IL-7R alpha+ progenitors. In
      contrast to IL-7R alpha, loss of the stem cell factor receptor c-kit was
      associated with enhanced lymphoid clonogenic potential and increased B-lineage
      differentiation potential. These results indicate that IL-7R alpha expression
      defines entry into a developmental stage characterized by upregulation of
      multiple lymphoid-associated genes and enhanced fitness for B-lymphoid
      differentiation. The onset of IL-7R alpha and PAX-5 expression immediately before
      acquisition of CD19 is consistent with evidence suggesting upregulation of CD19
      through pathways involving PAX-5 and IL-7.

PMID- 9028325
TI  - Chronic lymphocytic leukemia B cells are resistant to the apoptotic effects of
      transforming growth factor-beta.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia of the western
      world and is characterized by a slowly progressing accumulation of clonal CD5+ B
      cells. Our laboratory has investigated the role of transforming growth factor
      beta (TGF-beta) and interleukin-4 (IL-4) in the pathogenesis of B-cell expansion
      in CLL. In vitro addition of TGF-beta did not increase spontaneous apoptosis of B
      cells from most CLL patients, as determined using the TUNEL method, compared with
      a twofold increase observed in cultures of normal B cells. There was similar
      expression of TGF-beta type II receptors on both CLL B cells and normal B cells.
      In contrast to apoptosis, CLL B-cell proliferation was variably inhibited with
      addition of TGF-beta. In vitro addition of IL-4, previously reported to promote
      CLL B-cell survival, dramatically reduced spontaneous apoptosis of CLL B cells
      compared with normal B cells. CLL B-cell expression of IL-4 receptors was
      increased compared to normal B cells. Thus, our results show aberrant apoptotic
      responses of CLL B cells to TGF-beta and IL-4, perhaps contributing to the
      relative expansion of the neoplastic clone.

PMID- 9028326
TI  - Integration patterns of HTLV-I provirus in relation to the clinical course of
      ATL: frequent clonal change at crisis from indolent disease.
AB  - We examined human T-lymphotropic virus type I (HTLV-I) DNA integration in 68
      patients with adult T-cell leukemia/ lymphoma (ATL) by Southern blotting using
      EcoRI, which does not cut within the 9 kb of the genome and probes for pX and gag
      pol region of HTLV-I. We detected defective proviral integration as a monoclonal
      band of various sizes with the pX but not with the gag-pol probe, or a monoclonal
      band of less than 9 kb with the pX probe, in 20 patients (29.4%). These were
      designated defective (D) type. With both probes, a single band greater than 9 kb
      was detected in 34 (50.0%), designated complete (C) type, and two or more bands
      greater than 9 kb, were designated multiple (M) type, in 14 (20.6%). Advanced
      age, a high LDH value, and hypercalcemia were more frequent in D type patients.
      The median survival time (MST) was 6.8, 24.4, and 33.3 months, for D, C, and M
      types, respectively (log rank P = .006). Among 52 sequentially examined patients,
      the HTLV-I integration patterns changed in 4 (7.5%). In three of these four, the
      rearrangements of the T-cell receptor (TCR)b gene concomitantly changed,
      suggesting the appearance of a new ATL clone. Another patient had the same
      rearrangement of the TCRb gene, indicating clonal evolution. The HTLV-I
      integration pattern changed at crisis from indolent to aggressive ATL in three
      patients. These findings suggested that the HTLV-I integration patterns have
      clinical implications in ATL pathophysiology. In contrast to the clonal evolution
      characteristic of the multistep carcinogenesis of most human malignancies, the
      frequent clonal change of ATL at crisis is a peculiar phenomenon, probably
      reflecting the emergence of multiple premalignant clones in viral leukemogenesis
      as suggested in Epstein-Barr virus associated lymphomagenesis in the
      immunocompromised host.

PMID- 9028327
TI  - Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon
      alpha in chronic myelogenous leukemia.
AB  - Interferon-alpha (IFN-alpha) is an established treatment for chronic myelogenous
      leukemia (CML) in chronic phase, but the mechanism of its antileukemic activity
      is not clear. One possible mechanism of action might include the induction of
      apoptosis, and especially Fas-mediated cell killing may play an important role in
      the elimination of malignant cells. We investigated Fas receptor (Fas-R)
      expression and the consequences of Fas-R triggering in CML patients. Using two
      color flow cytometry, we found a significantly higher number of Fas-R-expressing
      CD34+ cells in the bone marrow (BM) of CML patients compared with normal
      subjects. We have previously shown that IFN-gamma induces Fas-R expression on
      CD34+ cells; in this study, we investigated whether IFN-alpha induces Fas-R
      expression on CML progenitor cells. Dose-dependent induction of Fas-R expression
      was observed after IFN-alpha stimulation of CD34+ cells from CML BM. In
      methylcellulose culture, IFN-alpha alone at a therapeutic concentration showed
      only marginal antiproliferative effects on both normal and CML BM progenitors. In
      contrast, a Fas-R agonist, the anti-CD95 monoclonal antibody CH11, inhibited
      colony formation from normal progenitors, and the inhibition was even stronger on
      CML progenitors. When CML BM cells were cultured in the presence of IFN-alpha,
      Fas-R-mediated inhibition of colony growth was potentiated in a dose-dependent
      fashion, consistent with IFN-alpha induction of Fas-R expression. This functional
      effect did not require the presence of accessory cells, since similar results
      were obtained with purified CD34+ cells. In suspension cultures, we demonstrated
      that suppression of CML hematopoiesis by IFN-alpha and Fas-R agonist was exerted
      through Fas-R-mediated induction of apoptosis. Our findings suggest that the Fas
      R/Fas-ligand system might be involved in the immunologic regulation of CML
      progenitor growth and that its effect can be amplified by IFN-alpha.

PMID- 9028328
TI  - Detection of cyclin D1 (bcl-1, PRAD1) overexpression by a simple competitive
      reverse transcription-polymerase chain reaction assay in t(11;14)(q13;q32)
      bearing B-cell malignancies and/or mantle cell lymphoma.
AB  - In mantle cell lymphoma, the t(11;14)(q13;q32) and its molecular counterpart, bcl
      1 rearrangement, are consistent features and lead to cyclin D1 (bcl-1, PRAD1)
      proto-oncogene overexpression. In order to detect cyclin D1 overexpression, we
      developed a simple assay involving a reverse transcription followed by
      competitive polymerase chain reaction (PCR). A single upstream primer was derived
      from a homologous region between cyclin D1 and the other D-type cyclins, cyclins
      D2 and D3, while three downstream primers were specific to their respective D
      type cyclins. Because the upstream primer was shared in PCR amplification of the
      three sequences, each PCR product served as a competitor and the quantification
      of the target was made by comparison of the intensity of the three products. With
      this assay we analyzed 45 hematopoietic cell lines and 40 clinical specimens.
      Cyclin D1 was rarely expressed in lymphoid cell lines except in t(11;14)(q13;q32)
      bearing B-cell malignancies and/or mantle cell lymphoma, which expressed cyclin
      D1 predominantly. In myeloid cell lines, the levels of cyclin D1 expression
      varied and never exceeded the sum of cyclin D2 and D3 levels. Cyclin D3 was
      ubiquitously expressed while cyclins D1 and D2 were differentially used. The
      observations suggest that human cyclin D3 may play a fundamental role in
      hematopoiesis and that cyclins D1 and D2 may have different lineage- or
      differentiation-dependent functions. With this assay, small aliquots of clinical
      specimens such as 100 microL peripheral blood were enough to detect cyclin D1
      overexpression without a well-controlled standard. The technique was validated as
      highly comparable with Northern analysis. This rapid and reliable detection of
      cyclin D1 overexpression may have practical clinical utility in the analysis and
      management of B-cell malignancies.

PMID- 9028329
TI  - Microsatellite instability is rare in B-cell non-Hodgkin's lymphomas.
AB  - Microsatellite instability (MSI), a symptom of defect in DNA mismatch repair
      function, represents a type of genomic instability frequently detected in many
      types of cancers. However, the involvement of MSI in non-Hodgkin's lymphomas
      (NHL) has not been conclusively investigated. In this study, we have tested the
      presence of MSI in 69 cases of B-cell NHL (B-NHL) representative of the various
      histologic categories of the disease and including 17 cases of acquired
      immunodeficiency syndrome (AIDS)-related B-NHL (AIDS-NHL). In addition, for
      selected B-NHL cases, consecutive samples obtained before and after clinical
      progression (with and without concomitant histologic transformation) were also
      investigated. Five distinct microsatellite repeats (2 dinucleotide, 2
      trinucleotide, and 1 tetranucleotide repeats) were analyzed by polymerase chain
      reaction in all cases. MSI, defined by the presence of microsatellite alterations
      in two or more of the five microsatellite loci tested, was not found in NHL. In
      contrast to a previous study reporting the frequent association between MSI and
      AIDS-NHL, we found this abnormality in only 1 of 17 cases of AIDS-NHL
      representative of the major subtypes. Overall, these data indicate that defects
      in DNA mismatch repair do not contribute significantly to the molecular
      pathogenesis of B-NHL.

PMID- 9028331
TI  - Hepatocyte growth factor/scatter factor promotes adhesion of lymphoma cells to
      extracellular matrix molecules via alpha 4 beta 1 and alpha 5 beta 1 integrins.
AB  - Hepatocyte growth factor (HGF)/scatter factor (SF) is the ligand for a tyrosine
      kinase cell surface receptor encoded by the MET protooncogene (c-MET). HGF/SF can
      induce proliferation and motility in epithelial cells and promotes invasion of
      carcinoma cells and NIH3T3 fibroblasts transfected with both HGF/SF and c-MET
      genes. Our results show that HGF/ SF and c-MET also play a role in adhesion and
      invasion of human lymphoma cells. c-MET mRNA is expressed in hemopoietic cells,
      such as hemopoietic progenitor cells (CD34+ cells) in bone marrow (BM) and
      mobilized peripheral blood, immature B cells in cord blood and BM, and germinal
      center B-centroblasts. In normal peripheral blood B cells, which are c-MET-, c
      MET expression was induced by PMA, ConA, HGF/ SF, and Epstein-Barr virus (EBV)
      infection. Using immunohistochemistry, we detected c-MET on the cell surface of
      large activated centroblasts in lymph nodes from patients with B-non-Hodgkin's
      lymphoma and Hodgkin's disease. In the latter group, c-MET expression correlated
      well with the presence of EBV. Because HGF/SF and c-MET promote metastasis of
      carcinoma cells, we studied the effects of c-MET stimulation by HGF/SF of B
      lymphoma cells on properties relevant for metastasis, ie, adhesion, migration,
      and invasion. HGF/SF stimulated adhesion of the c-MET+ B-cell lines to the
      extracellular matrix molecules fibronectin (FN) and collagen (CN) in a dose
      dependent manner. However, adhesion to laminin was not affected by HGF/SF.
      Adhesion to FN was mediated by beta 1-integrins alpha 4 beta 1 (VLA4) and alpha 5
      beta 1 (VLA5) since blocking antibodies against beta 1- (CD29), alpha 4-(CD49d),
      or alpha 5- (CD49e) integrin subunits, completely reversed the effect of HGF/SF.
      Furthermore, HGF/SF induced adhesion was abrogated by addition of genistein,
      which blocks protein tyrosine kinases, including c-MET. Addition of HGF/SF
      resulted in a sixfold increase in migration of c-MET B-lymphoma cells through
      Matrigel, compared to medium alone. In rat fibroblast cultures, HGF/SF doubled
      the number of c-MET+ B-lymphoma cells that invaded the fibroblast monolayer. In
      these adhesion, migration and invasion assays HGF/SF had no effect on c-MET- cell
      lines. In conclusion, c-MET is expressed or can be induced on immature,
      activated, and certain malignant B cells. HGF/SF increased adhesion of c-MET+ B
      lymphoma cells to FN and CN, mediated via beta 1-integrins alpha 4 beta 1 and
      alpha 5 beta 1, and furthermore promoted migration and invasion.

PMID- 9028330
TI  - Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T- and
      null-cell type and Hodgkin's disease: evidence for distinct cellular origin.
AB  - Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre,
      cells of T- or null-cell phenotype that show a preferential sinusoidal growth
      pattern and consistent CD30 positivity. Whether these tumors represent a single
      entity or several, and what the exact cell origin, is controversial. Recently,
      granzyme B, a cytotoxic granule component, was reported in a small percentage of
      ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To
      further investigate this possibility, we performed an immunohistochemical study
      of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic
      cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular
      proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL
      cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC)
      forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic
      antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17
      large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/ or CD30
      positivity. We found that 76% of ALCLs, representing all subtypes except the PC
      forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1
      and perforin were highly correlated (P < .001). On the basis of their
      immunophenotypic profiles, several subtypes of cytotoxic antigen positive and
      negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33)
      displayed an immunophenotypic profile consistent with cytotoxic T cells. Six
      cases expressed cytotoxic granular proteins in the absence of lineage specific
      markers, and one case expressed both T-cell- and natural killer cell-like
      markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic
      lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were
      cytotoxic granule protein negative. All but one of these displayed a T-cell
      phenotype. Cytotoxic granule protein expression did not correlate with the
      presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found
      to be TIA-1+, and none expressed perforin. Cytotoxic antigen expression was
      absent in LBCL. The expression of cytotoxic granule proteins in the majority of
      ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases
      originate from lymphocytes with cytotoxic potential. Furthermore, the
      demonstration of cytotoxic cell related proteins may be a useful addition to the
      current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL.

PMID- 9028332
TI  - Stat1 is induced and activated by all-trans retinoic acid in acute promyelocytic
      leukemia cells.
AB  - Treatment of freshly isolated acute promyelocytic leukemia (APL) cells and the
      myelogenous leukemia cell lines, NB4, HL-60, and U937, with all-trans retinoic
      acid (ATRA) results in a remarkable elevation in the amounts of Stat1 alpha and
      Stat2 proteins. Stat1 alpha protein levels are augmented by ATRA as a consequence
      of elevated amounts of the corresponding transcripts. The retinoid increases the
      levels of nuclear complexes that are capable of binding to interferon (IFN)
      regulated consensus sequences and contain Stat1 and/or Stat2 proteins, and causes
      a rapid and long-lasting elevation in Stat1 alpha tyrosine phosphorylation.
      Transient transfection experiments show that ATRA enhances the transactivating
      properties of Stat1 alpha observed on an appropriate reporter gene, in the
      presence of the RAR alpha retinoic acid receptor, but not in the presence of the
      PML-RAR protein. Treatment of NB4 cells with ATRA is associated with a remarkable
      upregulation of the two IFN-responsive genes IFN-responsive factor 1 and 2'-5'
      oligoadenylate synthetase, as well as with an augmentation in the levels of IFN
      alpha secretion. Our data show that ATRA is capable of modulating the amounts and
      the state of activation of some of the components of the IFN intracellular
      signaling pathways. They also suggest that the retinoid can bypass IFN/IFN
      receptor interactions and induce the expression of IFN-regulated genes.

PMID- 9028333
TI  - Defective transport is a common mechanism of acquired methotrexate resistance in
      acute lymphocytic leukemia and is associated with decreased reduced folate
      carrier expression.
AB  - Methotrexate (MTX) transport was examined in 27 patients with untreated acute
      lymphocytic leukemia (ALL) and 31 patients with relapsed ALL using a previously
      described fluorescent MTX analog (PT430) displacement assay (Blood 80:1158,
      1992). Only 13% of untreated patients were considered to have impaired MTX
      transport, whereas more than 70% of relapsed patients had evidence of impaired
      MTX transport. To further characterize the basis for this defect, Northern
      analyses for the reduced folate carrier (RFC) were performed on the RNA available
      from the leukemic blasts of 24 patients in whom MTX transport had been measured.
      Six of nine samples with impaired MTX transport had decreased RFC expression (one
      had no detectable RFC expression), while three had no decrease in RFC expression.
      None of 15 samples with normal MTX transport had decreased RFC expression. A
      reverse-transcriptase polymerase chain reaction (RT-PCR) assay was developed to
      quantitate RFC mRNA expression more accurately. Decreased RFC expression was
      demonstrated in six of the nine samples with impaired MTX transport, confirming
      the results obtained by Northern blot. These data indicate decreased RFC
      expression associated with impaired MTX transport is observed in relapsed ALL
      following treatment with MTX-containing therapy.

PMID- 9028334
TI  - Inactivation of recombinant monocyte cAMP-specific phosphodiesterase by cAMP
      analog, 8-[(4-bromo-2,3-dioxobutyl)thio]adenosine 3',5'-cyclic monophosphate.
AB  - Two cAMP analogs, 8- and 2- [(4-bromo-2,3-dioxobutyl)thio]adenosine 3',5'-cyclic
      monophosphate (8- and 2-BDB-TcAMP) have been used in probing the catalytic site
      of recombinant monocyte cAMP-specific phosphodiesterase (PDE4a). 2-BDB-TcAMP is a
      reversible and competitive inhibitor (Ki = 5.5 mumol/L) of cAMP hydrolysis by
      PDE4a, 8-BDB-TcAMP irreversibly inactivates the enzyme in a time- and
      concentration-dependent manner with a second order rate constant of 0.022 mmol/L
      1 min-1. The rate of inactivation of PDE4a is reduced by the presence of the
      substrate cAMP and specific inhibitors, rolipram and denbufylline, but not by
      cGMP or AMP. Reduction of the enzyme-inhibitor complex with sodium
      [3H]borohydride shows that 1.2 mol of the affinity label/mol of enzyme was
      incorporated. The radiolabeled peptide is composed of 10 amino acid residues (697
      to 706) located near the carboxyl end of the proposed catalytic domain. The
      peptide (GPGHPPLPDK) has seven nonpolar and aliphatic residues, of which four are
      proline, giving the peptide a highly structured conformation. This peptide is the
      first to be identified in the putative catalytic domain involved in substrate
      recognition.

PMID- 9028335
TI  - Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma
      receptor IIIb.
AB  - Polymorphic structures of the neutrophil Fc gamma receptor IIIb (Fc gamma RIIIb)
      result in alloantibody formation that causes alloimmune neonatal neutropenia and
      transfusion reactions. Alloantigens located on Fc gamma RIIIb include the
      antigens NA1 and NA2. In four cases of alloimmune neonatal neutropenia,
      granulocyte-specific alloantibodies directed against a thus far unknown antigen
      were detected by granulocyte agglutination and immunofluorescence tests in the
      maternal sera. By the use of the monoclonal antibody-specific immobilization of
      granulocyte antigens (MAIGA) assay, the new antigen, termed SH, was located on
      the Fc gamma RIIIb. Nucleotide sequence analysis of the Fc gamma RIIIb coding
      region from a SH(+) individual showed a single-base C-->A mutation at position
      266, which results in an Ala78Asp amino acid substitution. A family study
      confirmed that this nucleotide difference is inherited, and corresponds to the SH
      phenotype. Serologic typing of 309 randomly selected individuals showed an
      antigen frequency of 5% in the white population. The same frequency was found by
      genotyping, for which a technique based on polymerase chain reaction (PCR) using
      sequence-specific primers (PCR-SSP) was developed. Typing of all SH(+)
      individuals for NA1 and NA2, and PCR-restriction fragment length polymorphism
      analysis of the NA-specific PCR products from five SH(+) individuals using the SH
      specific endonuclease SfaN 1 showed that SH antigen is very probably the result
      of an additional mutational event in the NA2 form of the Fc gamma RIIIB gene.
      Immunochemical studies also demonstrated that the SH determinants reside on the
      65- to 80-kD NA2 isoform of the Fc gamma RIIIb. Our findings show the existence
      of an additional polymorphism of the Fc gamma RIIIb, which can result in
      alloantibody formation causing alloimmune neonatal neutropenia.

PMID- 9028336
TI  - Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in
      human neutrophils. I. Tyrosine phosphorylation-dependent stimulation of
      phosphatidylinositol 3-kinase and inhibition by phorbol esters.
AB  - Phosphatidylinositol 3-kinase (PI3-kinase) is a cytosolic enzyme that plays key
      roles in mediating signaling through many receptors. The heterodimeric form of
      PI3-kinase is made up of a regulatory subunit, p85, and a catalytic subunit,
      p110. Although granulocyte-macrophage colony-stimulating factor (GM-CSF) has been
      shown to activate PI3-kinase, the mechanisms by which this activation is mediated
      and regulated are incompletely understood. Here we show that treatment of human
      neutrophils with GM-CSF induced both time- and concentration-dependent increases
      in the level of tyrosine phosphorylation of p85. The ability of GM-CSF to
      activate PI3-kinase was abolished by pretreating the cells with erbstatin, a
      tyrosine kinase inhibitor. The simultaneous treatment of the cells with GM-CSF
      and phorbol esters such as phorbol 12-myristate 13-acetate (PMA) and phorbol
      12,13-dibutyrate (PDBu) significantly inhibited both the tyrosine phosphorylation
      of p85 and the activation of PI3-kinase. The inhibitory effects of phorbol esters
      were not induced by their inactive analogues and they were selective to the
      stimulation of tyrosine phosphorylation of p85 since phorbol esters did not alter
      the enhancement of the pattern of tyrosine phosphorylation of other cellular
      proteins, including that of Jak2 induced by GM-CSF. However, PMA significantly
      inhibited the in situ tyrosine phosphorylation and the activation of lyn observed
      in response to GM-CSF. The results suggest that the activation of PI3-kinase by
      GM-CSF is mediated by the tyrosine phosphorylation of p85 and that this
      activation is downregulated by PKC possibly via the inhibition of lyn.

PMID- 9028337
TI  - Protoporphyria induced by the orally active iron chelator 1,2-diethyl-3
      hydroxypyridin-4-one in C57BL/10ScSn mice.
AB  - Administration in the drinking water of the orally-active iron chelator 1,2
      diethyl-3-hydroxypyridin-4-one (CP94) to C57BL/10ScSn mice caused the development
      of hepatic protoporphyria. This was detected after 1 week and continued as long
      as the chelator was given (15 weeks). The more hydrophilic 1,2-dimethyl- and 1
      hydroxyethyl,2-ethyl-analogues (CP20 and CP102) were also tested, but they were
      both inactive in inducing accumulation of protoporphyrin in the liver.
      Restriction of in vivo iron supply for ferrochelatase seemed a likely mode of
      action, but an approximately 30% decrease in activity of this enzyme was also
      observed when measured in vitro. Extracts of livers from mice given CP20, CP94,
      and CP102 showed no potential to inhibit mouse ferrochelatase, in contrast to the
      findings with an extract from mice treated with the known porphyrogenic chemical
      4-ethyl-3, 5-diethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine, indicating that
      ferrochelatase inhibition did not occur by the formation of an N-ethyl
      protoporphyrin derived from metabolism by cytochrome P450, CP20, CP94, CP102, and
      CP117 (the pivoyl ester of CP102) all caused significant depression of the levels
      of ferritin-iron and total nonheme iron, but only CP94 caused the significant
      accumulation of protoporphyrin. Protoporphyria did not occur with iron overloaded
      C57BL/10ScSn mice or in SWR mice that had elevated basal iron status. Although
      the protoporphyrin had only a small effect on the total levels of the hemoprotein
      cytochrome P450 in C57BL/10ScSn mice, the activity of the CYP2B isoforms of
      cytochrome P450 was actually induced in both strains. The results show that CP94
      could cause protoporphyria in individuals of low iron status, perhaps through
      specifically targeting particular iron pools available to ferrochelatase and by
      concomitantly stimulating heme synthesis.

PMID- 9028338
TI  - Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of
      iron deficiency.
AB  - The objective of the study was to evaluate the diagnostic efficiency of
      laboratory tests, including serum transferrin receptor (TfR) measurements, in the
      diagnosis of iron depletion. The patient population consisted of 129 consecutive
      anemic patients at the University Hospital of Turku who were given a bone marrow
      examination. Of these patients, 48 had iron deficiency anemia (IDA), 64 anemia of
      chronic disease (ACD), and 17 patients had depleted iron stores and an infectious
      or an inflammatory condition (COMBI). Depletion of iron stores was defined as a
      complete absence of stainable iron in the bone marrow examination. Serum TfR
      concentrations were elevated in the vast majority of the IDA and COMBI patients,
      while in the ACD patients, the levels were within the reference limits reported
      earlier for healthy subjects. TfR measurement thus provided a reliable diagnosis
      of iron deficiency anemia (AUC(ROC) 0.98). Serum ferritin measurement also
      distinguished between IDA patients and ACD patients. However, the optimal
      decision limit for evaluation of ferritin measurements was considerably above the
      conventional lower reference limits, complicating the interpretation of this
      parameter. Calculation of the ratio TfR/log ferritin (TfR-F Index) is a way of
      combining TfR and ferritin results. This ratio provided an outstanding parameter
      for the identification of patients with depleted iron stores (AUC(ROC) 1.00). In
      anemic patients, TfR measurement is a valuable noninvasive tool for the diagnosis
      of iron depletion, and offers an attractive alternative to more conventional
      laboratory tests in the detection of depleted iron stores.

PMID- 9028339
TI  - Altered erythrocytes and a leaky block in B-cell development in CD24/HSA
      deficient mice.
AB  - The heat stable antigen (HSA, or murine CD24) is a glycosyl phosphatidylinositol
      linked surface glycoprotein expressed on immature cells of most, if not all,
      major hematopoietic lineages, as well as in developing neural and epithelial
      cells. It has been widely used to stage the maturation of B and T lymphocytes
      because it is strongly induced and then repressed again during their maturation.
      Terminally differentiated lymphocytes, as well as most myeloid lineages, are
      negative for HSA. Erythrocytes are an exception in that they maintain high levels
      of HSA expression. HSA on naive B cells has been shown to mediate cell-cell
      adhesion, while HSA on antigen-presenting cells has been shown to mediate a
      costimulatory signal important for activating T lymphocytes during an immune
      response. Here, we characterize mice that lack a functional HSA gene, constructed
      by homologous recombination in embryonic stem cells. While T-cell and myeloid
      development appears normal, these mice show a leaky block in B-cell development
      with a reduction in late pre-B and immature B-cell populations in the bone
      marrow. Nevertheless, peripheral B-cell numbers are normal and no impairment of
      immune function could be detected in these mice in a variety of immunization and
      infection models. We also observed that erythrocytes are altered in HSA-deficient
      mice. They show a higher, tendency to aggregate and are more susceptible to
      hypotonic lysis in vitro. In vivo, the mean half-life of HSA-deficient
      erythrocytes was reduced. When infected with the malarial parasite Plasmodium
      chabaudi chabaudi, the levels of parasite-bearing erythrocytes in HSA-deficient
      mice were also significantly elevated, but the mice were able to clear the
      infection with kinetics similar to wild-type mice and were immune to a second
      challenge. Thus, apart from alterations in erythrocytes and a mild block in B
      cell development, the regulated expression of HSA appears to be dispensable for
      the maturation and functioning of those cell lineages that normally express it.

PMID- 9028341
TI  - Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea.
      Multicenter Study of Hydroxyurea.
AB  - Hydroxyurea (HU) can increase fetal hemoglobin (HbF) in sickle cell anemia
      (HbSS). To identify determinants of the HbF response, we studied 150 HU-treated
      patients grouped by quartiles of change in HbF from baseline to 2 years. Half of
      the HU-assigned patients had long-term increments in HbF. In the top two
      quartiles, HbF increased to 18.1% and 8.8%. These patients had the highest
      baseline neutrophil and reticulocyte counts, and largest treatment-associated
      decrements in these counts. In the lower two quartiles, 2-year HbF levels (4.2%
      and 3.9%) and blood counts changed little from baseline. In the highest HbF
      response quartile, myelosuppression developed in less than 6 months, compliance
      was best, and final doses of HU were 15 to 22.5 mg/kg. All four quartiles had
      substantial increases of F cells in the first year. This was maintained for 2
      years only in the top three quartiles. Leukocyte and reticulocyte counts
      decreased initially in all quartiles, but drifted back toward baseline levels in
      the lowest HbF response quartile. Initial HbF level and phenotype of the F-cell
      production (FCP) locus were not associated with HbF response, but absence of a
      Central African Republic (CAR) haplotype was. Bone marrow ability to withstand HU
      treatment may be important for sustained HbF increases during HU treatment of
      HbSS.

PMID- 9028340
TI  - The primate erythrocyte complement receptor (CR1) as a privileged site: binding
      of immunoglobulin G to erythrocyte CR1 does not target erythrocytes for
      phagocytosis.
AB  - The primate erythrocyte (E) complement receptor, CR1, is a transmembrane
      glycoprotein located in clusters on the surface of E. In vivo studies have
      demonstrated that during processing and clearance of complement-opsonized immune
      complexes, large amounts of immunoglobulin G (IgG) can be bound to primate E via
      CR1 with no E loss or lysis. However, when comparable amounts of IgG are bound to
      other sites on E, in many cases the E are cleared from the circulation by the
      mononuclear phagocytic system. Therefore, due to its role in immune complex
      processing, CR1 may represent a privileged site on the primate E. To delineate
      further this property of E CR1, we performed in vitro phagocytosis assays in the
      absence of complement and examined the ingestion of E, opsonized at various sites
      with IgG, by peripheral blood monocytes. When either human or rhesus monkey E
      were opsonized at sites other than CR1, with between 1,000 and 15,000 IgG per E,
      substantial phagocytosis of E was evident. However, when comparable amounts of
      IgG were bound exclusively via CR1, little, if any, phagocytosis was observed.
      The key to the low phagocytic level of E opsonized via CR1 may be related to the
      requirements of a "zipper mechanism" for phagocytosis first annunciated by
      Griffin et al. Based on their findings, we suggest that due to the presence of
      preexisting clusters of CR1 on the E membrane, large amounts of IgG can be bound
      to E under conditions that preclude circumferential engagement (and phagocytosis)
      of the entire E by Fc receptors on the monocyte.

PMID- 9028342
TI  - A murine model for human cord blood transplantation: near-term fetal and neonatal
      peripheral blood cells can achieve long-term bone marrow engraftment in
      sublethally irradiated adult recipients.
AB  - The purposes of the research reported here were first to explore a murine model
      for human placental and umbilical cord blood transplantation and second to
      evaluate the engraftment ability of ex vivo cultured hematopoietic cells. Murine
      near-term fetal and neonatal peripheral blood (FNPB) cells, genetically marked
      with the human multiple drug resistance transgene (MDR1) were used for syngeneic
      transplants into sublethally irradiated adult mice. Donor cells were transplanted
      either fresh and untreated, or after ex vivo culture in the presence of the
      hematopoietic growth factors recombinant murine stem cell factor, recombinant
      human interleukin-3 (rHu IL-3), and rHu IL-6, in a liquid culture system. To
      evaluate, count, and characterize FNPB progenitor cell-derived colonies, neonatal
      mouse mononuclear cells were cultured directly in methylcellulose with growth
      factors. To assess their ex vivo expansion ability, FNPB mononuclear cells were
      first cultured in liquid medium for 3 to 8 days and then transferred to semisolid
      assay plates. Evaluation of the cell counts after liquid culture showed a 1.4- to
      11.6-fold increase, and the numbers of colonies observed in methylcellulose were
      similar to those produced by fresh FNPB cells. Donor-type engraftment was
      demonstrated by polymerase chain reaction (PCR) amplification of the human MDR1
      transgene in the peripheral blood of all surviving animals (5 of 7 recipients of
      the fresh, and 3 of 8 recipients of the ex vivo-cultured cells) 2 to 4 months
      after transplantation. The proportion of donor leukocytes in the peripheral blood
      of the recipients (chimerism) was evaluated using fluorescence in situ
      hybridization (FISH) analysis 4 to 6 months after transplantation and ranged from
      2% to 26%. In addition, bone marrow cultures were obtained from two recipient
      animals: one had received fresh-untreated cells and was evaluated 8 months after
      transplant, the other had received ex vivo cultured cells and was tested 14
      months after grafting. The derived hematopoietic colonies were tested by PCR and
      the transgene was detected, conclusively proving long-term engraftment of donor
      cells. These results indicate that FNPB transplants can be successfully performed
      in sublethally irradiated mice with and without ex vivo culture. Long-term donor
      type engraftment with sustained chimerism has been demonstrated. Thus, murine
      neonatal blood grafts can be used as an animal model for cord blood
      transplantation for gene therapy studies where complete myeloablation is not
      desirable and partial replacement of defective marrow may be sufficient.
      Furthermore, the possibility of numerically expanding hematopoietic progenitor
      cells contained in neonatal blood without affecting their engraftment ability
      could facilitate use of cord blood grafts in adult recipients.

PMID- 9028343
TI  - Donor gamma delta T lymphocytes promote allogeneic engraftment across the major
      histocompatibility barrier in mice.
AB  - T cells that express the alpha beta T-cell receptor are thought to be the T-cell
      population primarily responsible for facilitating alloengraftment. The role of
      gamma delta + T cells that comprise only a minority of mature T cells in
      promoting allogeneic engraftment, however, has not been extensively studied. The
      purpose of this study was to determine whether gamma delta T cells were capable
      of facilitating alloengraftment in murine recipients of major histocompatibility
      complex-mismatched marrow grafts. We developed a model where engraftment of
      C57BL/6 x 129/F2(H-2b) marrow in sublethally irradiated (800 cGy) recipients
      (AKR/J, H-2k) is dependent on the presence of mature donor T cells in the marrow
      graft. In this model, donor T-cell engraftment was significantly augmented by as
      few as 1 x 10(5) alpha beta T cells. The role of gamma delta T cells was then
      investigated using transgenic donors (C57BL/6 x 129 background) in which a
      portion of the T-cell receptor-beta chain gene was deleted by gene targeting so
      that these mice lack alpha beta T cells. Addition of 10 x 10(5) naive gamma delta
      T cells to T-cell depleted marrow grafts was required to significantly increase
      alloengraftment, although donor T cells averaged < 50% of total splenic T cells.
      To determine whether higher doses of gamma delta T cells would improve donor
      engraftment and eradicate residual host T cells, gamma delta T cells were ex vivo
      expanded with a gamma delta T-cell-specific mono-clonal antibody and interleukin
      2 and then transplanted into irradiated recipients. Transplantation of > or = 160
      x 10(6) activated gamma delta T cells was necessary to consistently and
      significantly augment donor cell chimerism and enhance hematopoietic
      reconstitution when compared to control mice, but host T cells persisted in these
      chimeras. Addition of 2.5 x 10(4) mature alpha beta T cells, which alone were
      incapable of facilitating engraftment, to T-cell depleted marrow grafts
      containing 160 x 10(6) activated gamma delta T cells resulted in long-term (> 100
      day) complete donor engraftment, indicating that limiting numbers of alpha beta T
      cells were required in the marrow graft for the eradication of residual host T
      cells. Using serial weight curves and B-cell reconstitution as end points,
      clinically significant graft-versus-host disease was not observed in these
      chimeras under these experimental conditions. These data show that, whereas less
      potent than alpha beta T cells, gamma delta T cells are able to promote
      engraftment and enhance hematopoietic reconstitution in allogeneic marrow
      transplant recipients.

PMID- 9028344
TI  - Interferon-alpha upregulates both interleukin-10 and interferon-gamma production
      by human CD4+ T cells.

PMID- 9028345
TI  - In vitro hypersensitivity to oxygen of Fanconi anemia (FA) cells is linked to ex
      vivo evidence for oxidative stress in FA homozygotes and heterozygotes.

PMID- 9028346
TI  - Platelet antibody testing in idiopathic thrombocytopenic purpura.

PMID- 9028347
TI  - Microsatellite instability in natural killer cell-like T-cell lymphomas in
      immunocompromised and immunocompetent individuals.

PMID- 9028348
TI  - Nephrotic syndrome as a complication of immune tolerance in hemophilia B.

PMID- 9028349
TI  - Transient increase of leukocytes after transplantation of expanded and
      nonexpanded allogeneic CD34+ blood cells is of host origin.

PMID- 9028350
TI  - p53 protein accumulation and p53 gene mutation in esophageal carcinoma. A
      molecular and immunohistochemical study with clinicopathologic correlations.
AB  - BACKGROUND: p53 gene mutation and p53 protein accumulation are common in human
      cancer. However, their clinical significance is controversial and p53
      accumulation may not correlate with gene mutation. The current study investigates
      the occurrence of p53 alterations in esophageal carcinoma, the correlation
      between the analyses at the gene and protein level, and their prognostic
      significance. METHODS: A series of 74 esophageal carcinomas (46 squamous cell
      carcinomas, 21 Barrett's adenocarcinomas, and 7 undifferentiated carcinomas) was
      studied by single strand conformation polymorphism (SSCP) analysis and
      immunohistochemistry (IHC) to detect p53 mutation and accumulation, respectively.
      RESULTS: p53 mutations in exons 5-8 were detected in 53% of the carcinomas
      whereas p53 accumulation was observed in 57% of cases. Comparing SSCP and IHC,
      there were 27 discordant cases (38%). Overall, only 20 tumors (27%) did not
      display p53 mutation and/or p53 accumulation. No associations were found between
      p53 aberrations and clinicopathologic parameters, including patients age and
      gender tumor type, stage, and grade. p53 protein accumulation and p53 gene
      mutation were not related to patient survival by univariate or multivariate
      analysis in esophageal carcinomas. CONCLUSIONS: p53 aberrations are very common
      in esophageal carcinomas. However, p53 gene mutation and p53 protein accumulation
      have a significant discordance, suggesting that p53 function may be inactivated
      by mechanisms other than mutation. p53 aberrations do not independently predict
      prognosis in esophageal tumors.

PMID- 9028351
TI  - Differential expression of apoptosis receptors on diffuse and intestinal type
      stomach carcinoma.
AB  - BACKGROUND: Intestinal and diffuse adenocarcinomas of the stomach differ in
      phenotypic properties, morphology, and growth behavior. Apoptosis (programmed
      cell death) is induced via specific cell-surface receptors (SC-1, Fas/APO-1/CD95)
      and coregulated by intracellular molecules (bcl-2, p53, etc.); the success of
      apoptotic processes is dependent on the expression of these signals. Differences
      in the expression of specific apoptosis receptors and intracellular-related
      signals might help to explain the molecular pathogenesis of these two types of
      stomach adenocarcinoma. METHODS: Immunohistochemical studies were performed on
      frozen sections of tumor tissue using human monoclonal antibody SC-1 and murine
      monoclonal antibodies Fas and p53, followed by peroxidase-coupled second
      antibodies. To determine binding of SC-1 and Fas antibodies to stomach carcinoma
      cells on the molecular level, Western blot analysis was performed with cell
      extract preparations from stomach carcinoma cells. To investigate functional
      apoptotic activity, MTT assays were performed with SC-1 and Fas antibodies on
      stomach carcinoma cells. RESULTS: On frozen sections intestinal type stomach
      carcinoma cells demonstrate little or no expression of SC-1 and Fas receptors (4
      of 17 and 1 of 17, respectively). Diffuse type stomach carcinoma cells show just
      the opposite: greater than 50% express SC-1 and Fas at a high level (15 of 30 and
      22 of 30, respectively). Normal stomach mucosa is negative with both antibodies.
      Expression of p53 is positively correlated with intestinal type carcinomas (11 of
      17) but not with diffuse type (5 of 30). In functional studies MTT assay) the SC
      1 and Fas antibodies react with stomach carcinoma by inducing apoptosis and
      inhibiting growth. On Western blot analysis of extracts from stomach carcinoma
      cells, SC-1 detects a protein of 50 kilodalton (kD) and Fas proteins of
      approximately 30, 45, and 60 kD. CONCLUSIONS: These data indicate that gastric
      carcinoma cells of the intestinal and diffuse type differ in their expression of
      the apoptotic receptors SC-1 and Fas and the tumor suppressor gene product p53.
      These new data on phenotypic differences support the hypothesis that these two
      types of stomach carcinoma do not only differ in morphology, growth pattern, and
      risk factors but also in genetic pathways.

PMID- 9028352
TI  - Incidence of colorectal adenocarcinoma by anatomic subsite. An epidemiologic
      study of time trends and racial differences in the Detroit, Michigan area.
AB  - BACKGROUND: Colorectal adenocarcinoma may represent more than one disease
      process. Numerous epidemiologic studies suggest that rates of occurrence of
      colorectal adenocarcinoma at particular anatomic subsites (e.g., right colon,
      left colon, and rectum) may be associated with distinctive geographic,
      demographic, and risk factor profiles. This study explored time trends over a 22
      year period of the incidence of adenocarcinoma of the colon and rectum at various
      subsites among patients of different race, gender, and stage of disease. METHODS:
      Data on the incidence of colorectal adenocarcinoma were obtained from a
      population-based cancer registry in the Detroit, Michigan area funded by the
      National Cancer Institute. Age-adjusted incidence rates were analyzed by year of
      diagnosis. Relative survival rates were also obtained for different race and
      gender categories, along with disease stage at diagnosis. RESULTS: A major rise
      was revealed in the incidence of adenocarcinoma in the right colon among African
      American men and women between the mid-1970s and the early 1980s. The rise was
      greatest among African American men and accounts for increases in late stage
      disease among them. Corresponding decreases in survival among African American
      men were noted. CONCLUSIONS: These findings indicated widely differing disease
      patterns based on anatomic subsite and patient demography and also indicated a
      need for targeted efforts at early detection of adenocarcinoma of the right colon
      among African Americans.

PMID- 9028353
TI  - Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma.
AB  - BACKGROUND: The metabolism of sphingomyelin generates important signals
      regulating cell proliferation and apoptosis. Previous studies found that the
      administration of colon carcinoma carcinogen was associated with an accumulation
      of membrane sphingomyelin, and that dietary sphingomyelin inhibited promotion of
      experimental colon carcinoma in mice, indicating that the abnormal metabolism of
      sphingomyelin is linked to colon carcinoma development. However, the changes in
      sphingomyelinase (SMase) activity in colon carcinoma have not been directly
      studied. The authors identified, specifically in the intestine, a distinctive
      alkaline SMase that differs from the known acidic and neutral SMases. The
      functions and clinical implications of the enzyme are unknown. This study
      examined the changes in all three SMase activities in human colorectal carcinoma.
      METHODS: Tissue samples were taken from colorectal carcinoma and normal mucosa
      from 18 patients. After homogenization, the activities of acidic, neutral, and
      alkaline SMase, as well as ceramidase and alkaline phosphatase, were determined.
      The enzyme activities in cancer tissue were compared with normal tissue from the
      same patients. RESULTS: In the normal tissue, there is an activity gradient from
      the ascending colon to the rectum for neutral and alkaline SMases but not for
      acidic SMase. In colorectal carcinoma, alkaline SMase activity was preferentially
      decreased by 75%, whereas acidic and neutral SMase activity decreased by 30% and
      50%, respectively. No changes could be found for either ceramidase or alkaline
      phosphatase activity. CONCLUSIONS: Alkaline SMase activity preferentially
      decreases in human colorectal carcinoma, suggesting a regulatory role of the
      enzyme in colon mucosa cell proliferation.

PMID- 9028354
TI  - Diagnosis of carcinoma in situ of the pancreas by peroral pancreatoscopy and
      pancreatoscopic cytology.
AB  - BACKGROUND: Most pancreatic carcinomas are unresectable at the time of diagnosis,
      but recently the diagnosis of carcinoma in situ of the pancreas has become
      possible. This diagnosis can be made by the detection of cancer cells in
      pancreatic juice and the radiographically demonstrated lack of a mass lesion. It
      has greatly improved the effectiveness of surgery. Carcinoma in situ remains
      within the pancreatic ductal epithelium and has not yet invaded the parenchyma.
      However, it has often been difficult to locate carcinoma in situ by conventional
      diagnostic methods, such as ultrasonography, endoscopic ultrasonography, computed
      tomography, and endoscopic retrograde pancreatography. METHODS: Peroral
      pancreatoscopy and a new method of cytodiagnosis, pancreatoscopic cytology, were
      used to analyze 11 patients with carcinoma in situ of the pancreas, 10 with
      disease in the main duct of the pancreas and 1 with disease in the branch ducts.
      The results of pancreatoscopic cytology were compared with those of conventional
      pancreatic juice cytology. RESULTS: Under peroral pancreatoscopy, carcinoma in
      situ of the pancreas in the main duct appeared as papillary mucosa, irregular
      mucosa, or nodular mucosa. Using pancreatoscopic cytology, cancer cells were
      obtained from all the lesions, allowing a more thorough analysis than pancreatic
      juice cytology. CONCLUSIONS: Peroral pancreatoscopy and pancreatoscopic cytology
      are useful for locating and diagnosing carcinoma in situ of the pancreas.

PMID- 9028355
TI  - Correlation between K-ras gene mutation and prognosis of patients with nonsmall
      cell lung carcinoma.
AB  - BACKGROUND: Mutations at codons 12, 13, and 61 of the three ras genes, H-ras, K
      ras, and N-ras, convert these genes into active oncogenes. It appears that ras
      gene mutations can be found in a variety of tumor types. The purpose of this
      study was to evaluate the clinical significance of K-ras gene mutation in
      nonsmall cell lung carcinoma (NSCLC). METHODS: The authors analyzed 58 NSCLC
      patients for mutations at codons 12, 13, and 61 of the K-ras gene and correlated
      the findings with the tumor stage and patient survival. Polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP) and the direct nucleotide
      sequencing method were used to detect mutations after amplification of ras
      specific sequences by PCR. RESULTS: Fourteen mutations (24%) of ras genes were
      found, all at codon 12 of the K-ras gene. GGT to GAT transition was the
      predominant mutational pattern. There was a significant association between K-ras
      mutation and the tumor stage (i.e., the higher the stage, the higher the mutation
      rate) (P = 0.014). Using univariate analysis, the presence of K-ras mutation in
      paraffin embedded tissue from patients who received treatment with curative
      intent was associated with a shorter survival (P = 0.039). The median survival
      duration for patients with or without K-ras mutation was 9 and 30 months,
      respectively. The Cox proportional hazards model also predicted a higher risk for
      patients with K-ras mutations (P = 0.047). CONCLUSIONS: K-ras mutations, present
      in a subset of NSCLC, are associated with tumor progression and shortened patient
      survival.

PMID- 9028356
TI  - The prognostic application of cytokeratin typing of nonsmall cell lung carcinoma.
      A retrospective study.
AB  - BACKGROUND: In a previous study, the authors used a variety of anticytokeratin
      monoclonal antibodies to show that a large proportion of lung tumors
      cytologically diagnosed as squamous cell carcinoma contain cells expressing
      simple epithelial cytokeratins, suggesting that these tumors have their origin in
      adenocarcinoma. These findings raised the possibility that cytokeratin (CK)
      typing might have a diagnostic capacity not attainable by standard
      histopathology. The aim of the current study was to assess the value of CK typing
      for this purpose by determining the correlation between the diagnosis of lung
      tumors based on CK typing and the survival rate of the patients. METHODS:
      Paraffin embedded tissue sections of 66 nonsmall cell lung carcinoma (NSCLC)
      specimens were examined. These included 18 adenocarcinomas, 32 squamous cell
      carcinomas, and 16 undifferentiated carcinomas, all diagnosed surgically and
      histopathologically, and further classified as either Stage I or II. CK typing
      was performed using the streptavidin-biotin-peroxidase method, employing the
      following anti-CK monoclonal antibodies: Ks.B.17 (which reacts with CK 18), A3-3
      (which reacts with CK 13), and E5-9 (which reacts with CK 10). RESULTS:
      Comparison between the 5-year survival rates (5 ysr) of patients with different
      NSCLC indicated that all types of Stage II tumors had a much poorer prognosis
      than Stage I tumors. Differences found in the 5 ysr among patients with different
      types of Stage I tumors were not statistically significant (adenocarcinomas, 33%
      5 ysr; squamous cell carcinomas, 59% 5 ysr; undifferentiated carcinomas, 36% 5
      ysr; all diagnosed by conventional histopathology). Similarly, no significant
      differences were noted in 5 ysr between patients with tumors stained positively
      or negatively with monoclonal antibodies A3-3 or E5-9 (anti-CK 13 and anti-CK 10,
      respectively). In contrast, highly significant differences (P = 0.002) were found
      in the 5 ysr between patients with Stage I tumors positively or negatively
      stained with monoclonal antibody Ks.B.17 (23% vs. 75% 5 ysr, respectively)
      regardless of the histologic types of tumors. Especially informative was a
      combination of immunohistochemical and histologic diagnoses, with best survival
      rates (87% 5 ysr) in Ks.B.17 negative tumors histologically diagnosed as Stage I
      squamous cell carcinomas and worst survival rates (14% 5 ysr) in Ks.B.17 positive
      tumors diagnosed as adenocarcinomas. CONCLUSIONS: The current study showed that
      CK 18 typing of lung tumors can provide a more accurate diagnosis and therefore
      facilitate the planning of more suitable therapeutic approaches.

PMID- 9028357
TI  - Autologous tumor killing activity as a prognostic factor in primary resected
      nonsmall cell carcinoma of the lung.
AB  - BACKGROUND: Cytotoxic activity of peripheral blood lymphocytes obtained during
      surgery against autologous fresh tumor cells has been reported. However, the role
      of lymphocyte autologous tumor killing or natural killer activity during the
      postoperative period remains obscure. In this article, the authors describe the
      importance of postoperative autologous tumor killing activity as a prognostic
      factor in patients with primary resected nonsmall cell lung carcinoma (NSCLC)
      after long term follow-up. METHODS: Forty-two patients who had resection of
      NSCLC, with primary culture of autologous tumor cells taken successfully, were
      studied. Cytotoxic activity against autologous, allogenic NSCLC and K562 leukemia
      cells was examined using peripheral blood lymphocytes obtained during the 2 weeks
      immediately following surgery. Factors related to prognosis were analyzed by
      univariate and multivariate analyses. RESULTS: The overall 5- and 10-year
      survival rates for the NSCLC patients were 40.5% and 27.5%, respectively.
      Statistical analysis of survival curves revealed a significant difference with
      regard to T classification (P = 0.025), N classification (P = 0.0015), stage (P =
      0.028), and postoperative autologous tumor killing activity (P = 0.0008); there
      were no significant differences in relation to age, gender, histology,
      differentiation, visceral pleural invasion, resectability, surgical method,
      allogeneic tumor killing activity, or natural killer activity. Multivariate
      analysis demonstrated a significant correlation between disease recurrence and N
      classification (P = 0.0003), T classification (P = 0.023), stage (P = 0.001), and
      autologous tumor killing activity (P = 0.007), indicating independent prognostic
      significance. The phenotypes of the effector cells involved in autologous tumor
      killing activity were CD3(+), CD4(-), CD8(+), and CD11b(-). Autologous tumor
      killing activity was inhibited by competing unlabeled autologous tumor cells.
      CONCLUSIONS: Autologous tumor killing activity during the 2 weeks immediately
      following surgery is an important prognostic factor in resected NSCLC.

PMID- 9028358
TI  - Malignant fibrous histiocytoma of bone. A clinicopathologic study of 81 patients.
AB  - BACKGROUND: Malignant fibrous histiocytoma of bone, a relatively rare primary
      malignant neoplasm occurring in bone, is a distinct clinicopathologic entity
      formerly included in the category of osteosarcoma or fibrosarcoma. A series of
      patients treated at the Mayo Clinic for malignant fibrous histiocytoma of bone
      was studied to determine whether the prognosis for this disease is different from
      that of osteosarcoma and whether treatment should be different. METHODS: The bone
      tumor files of the Mayo Clinic were reviewed for examples of malignant fibrous
      histiocytoma of bone. Clinical records and histologic slides were reviewed for 81
      patients. Roentgenograms of 13 patients were available for review. RESULTS:
      Patients with malignant fibrous histiocytoma of bone ranged in age from 6 to 81
      years. The region most commonly affected was the knee. Seventy-eight percent of
      the lesions arose de novo and 22% in preexisting conditions. Histologically, most
      of the tumors were classified as the storiform pleomorphic type, although other
      histologic subtypes were identified. The prognosis depended on the types of
      surgical margins involved. Patients with wide or radical margins had a better
      prognosis than patients in whom the margins were contaminated. Some patients who
      received radiation therapy alone became long term survivors. CONCLUSIONS: The
      overall prognosis for patients with malignant fibrous histiocytoma was not found
      to be significantly different from that described for patients with osteosarcoma
      in recent series. However, at least in this small series, some patients with
      malignant fibrous histiocytoma had a good response to radiation therapy.
      Osteosarcoma is generally considered radioresistant.

PMID- 9028359
TI  - Association of Stein-Leventhal syndrome with the incidence of postmenopausal
      breast carcinoma in a large prospective study of women in Iowa.
AB  - BACKGROUND: The Stein-Leventhal syndrome (SLS), first described in 1935, is
      characterized by infertility, hyperandrogenization, and obesity. Because this
      phenotype represents an aggregation of risk factors for postmenopausal breast
      carcinoma, and because in general, a hormonal imbalance underlies the disorder,
      the authors examined the association between self-reported SLS and breast
      carcinoma incidence in a cohort of 34,835 cancer-free women assembled in 1986 and
      followed through 1992. METHODS: All participants were between the ages of 55 and
      69 and held a valid Iowa driver's license. A total of 472 women in the cohort
      (1.35%) reported a history of SLS at baseline. Incident cases of breast carcinoma
      were identified annually using the State Health Registry of Iowa. Data were
      analyzed using Cox proportional hazards regression. RESULTS: During the follow-up
      period, there were 883 incident breast carcinomas, 14 among women reporting a
      history of SLS. Women with SLS were more likely than women without SLS to report
      fertility problems and menstrual irregularities, but there were no significant
      differences observed regarding body mass index (BMI). Although women with SLS
      were 1.8 times as likely to report benign breast disease than women without SLS
      (P < 0.01), they were not more likely to develop breast carcinoma (relative risk
      [RR] = 1.2; 95% confidence interval [CI] = 0.7-2). Adjustment for age at
      menarche, age at menopause, parity, oral contraceptive use, BMI, waist-to-hip
      ratio, and family history of breast carcinoma lowered the RR to 1 (95% CI = 0.6
      1.9. CONCLUSIONS: Despite the high risk profiles of some women with SLS, these
      results do not suggest that the syndrome per se is associated with an increased
      risk of postmenopausal breast carcinoma.

PMID- 9028360
TI  - Pelvic computed tomography of breast carcinoma patients. Should it routinely be
      added to abdominal computed tomography?
AB  - BACKGROUND: This study was conducted to determine if pelvic computed tomography
      (CT) should routinely be appended to abdominal CT in the workup of patients with
      breast carcinoma. METHODS: The abdominal-pelvic CTs of 139 breast carcinoma
      patients (195 exams) were reviewed. Scans were grouped by indication and whether
      pelvic pathology was known before CT. Pelvic CT results were correlated with
      their effect on patient management. RESULTS: Among the 119 patients without pre
      CT evidence of pelvic disease, a nonosseous pelvic metastasis was identified in
      only 1; this patient also had liver metastases and management was not changed. No
      unsuspected pelvic CT finding altered therapy for breast carcinoma. However,
      three patients underwent surgery for asymptomatic masses discovered on pelvic CT;
      all were benign. CONCLUSIONS: Pelvic CT is unlikely to affect the management of
      patients with breast carcinoma by detecting occult metastatic disease.

PMID- 9028361
TI  - Adenocarcinoma of the cervix. Expression and clinical significance of estrogen
      and progesterone receptors.
AB  - BACKGROUND: Although hormone receptor status is an important prognostic indicator
      in adenocarcinoma of the breast and the endometrium, few studies have
      investigated the expression and clinical significance of estrogen receptor (ER)
      and progesterone receptor (PgR) in adenocarcinoma of the cervix. METHODS: ER and
      PgR expression were determined using an immunohistochemical method in 84 cervical
      adenocarcinomas. Clinical features and outcome were determined by chart review.
      RESULTS: ER was identified in 17 of the 84 cases (20%). ER positivity was most
      frequently detected in mucinous adenocarcinoma of the endocervical type (in 11 of
      48 cases) and endometrioid adenocarcinoma (in 4 of 10 cases). PgR was identified
      in 23 of the 84 cases (27%). PgR positivity was also most frequently detected in
      mucinous adenocarcinoma of the endocervical type (in 15 of 48 cases) and
      endometrioid adenocarcinoma (in 6 of 10 cases). Mucinous adenocarcinoma of the
      intestinal type (five cases), glassy cell carcinoma (two cases), and clear cell
      adenocarcinoma (two cases) were uniformly negative for both ER and PgR. No
      association was detected between International Federation of Gynecology and
      Obstetrics stage and receptor status, but there was a somewhat lower frequency of
      ER positivity in poorly differentiated tumors (P = 0.07). No association was
      detected between PgR status and disease free survival. Similarly, no association
      between ER status and overall survival was observed. Although ER positive tumors
      may be associated with longer disease free survival than ER negative tumors, this
      difference did not reach statistical significance in this study (P = 0.06).
      CONCLUSIONS: ER and PgR positivity were found in 20% and 27%, respectively, of
      primary cervical adenocarcinomas. However, receptor status was not significantly
      associated with either overall survival or disease free survival.

PMID- 9028362
TI  - Correlation of cervical carcinoma c-erb B-2 oncogene with cell proliferation
      parameters in patients treated with radiation therapy for cervical carcinoma.
AB  - BACKGROUND: Although c-erb B-2 oncoprotein expression (CerbB-OPE) is believed to
      be associated with tumor cell proliferation and prognosis, the correlation
      between CerbB-OPE and cell proliferation parameters has not been fully analyzed.
      METHODS: Immunohistochemical studies were performed on 64 cervical carcinoma
      patients treated with radiation therapy. Prognosis was analyzed by CerbB-OPE,
      growth fraction determined with Ki-67 immunohistochemistry (Ki-GF), and the
      mitotic index of proliferating cell population (pMI). RESULTS: CerbB-OPE was
      observed on the cell membrane of carcinoma cells. Positivity of CerbB-OPE, which
      was 42.4% in total, increased significantly with stage progression. No
      significant differences were observed among histologic subtypes. Mean total Ki-GF
      and pMI were 36% and 2.5%, respectively. Mean Ki-GF for CerbB(+) patients was
      26.2%, which was significantly lower than the 38.3% for CerbB(-) patients (P <
      0.01). The mean pMI for CerbB(+) patients was 3.7%, which was significantly
      higher than the 2% for CerbB(-) patients (P < 0.05). The 5-year survival rates of
      CerbB(+) patients and CerbB(-) patients were 45.1% and 75.6%, respectively,
      indicating that CerbB(+) patients showed significantly poorer survival than
      CerbB(-) patients (P < 0.01). The difference in survival was due mainly to local
      recurrence rather than distant metastasis. There were significant correlations
      between prognosis and Ki-GF and pMI. CONCLUSIONS: The poor prognosis of patients
      with cervical carcinoma with CerbB-OPE was due to local recurrences after
      radiation therapy. The correlations of CerbB-OPE with Ki-GF and pMI suggest that
      c-erb B-2 oncoprotein may play an important role in the cell proliferation status
      of cervical carcinoma.

PMID- 9028363
TI  - Glutathione S-transferase-pi expression and glutathione concentration in ovarian
      carcinoma before and after chemotherapy.
AB  - BACKGROUND: To clarify the role of glutathione (GSH) in the chemotherapy
      resistance of ovarian carcinoma, the authors examined the expression of
      glutathione S-transferase-pi (GST-pi) and the concentration of glutathione in
      tumors before and after chemotherapy in the same patients. METHODS: The cohort
      for this study comprised 20 patients with ovarian carcinoma who had residual
      disease after primary surgery. These patients received two to three courses of
      postoperative chemotherapy, then underwent surgery for a second time.
      Chemotherapy consisted of 50 mg/m2 cisplatin, 40 mg/m2 doxorubicin, and 400 mg/m2
      cyclophosphamide. The expression of GST-pi in tumors was determined by
      immunohistochemical staining and Western blot analysis. GSH concentration was
      measured by an enzymatic assay. RESULTS: Of the 20 patients, 10 responded to
      chemotherapy and 10 did not. Immunohistochemical staining for GST-pi was positive
      in 3 tumors among the 10 responders and in 7 tumors among the 10 nonresponders,
      but Western blot analysis detected GST-pi expression in all tumors. Among the
      responders, GST-pi after chemotherapy increased in one patient, was unchanged in
      two patients, and decreased in seven patients. Among nonresponders, GST-pi
      increased in six patients, was unchanged in one patient, and decreased in three
      patients. The ratio of GST-pi density in tumors after chemotherapy to GST-pi
      density before chemotherapy was significantly higher in nonresponders than in
      responders (2.0 +/- 1.1 vs. 0.6 +/- 0.4). The concentration of GSH in tumors was
      widely distributed, but it was found that the ratio of GSH concentration in each
      tumor after chemotherapy to GSH concentration before chemotherapy was
      significantly higher for nonresponders than for responders (3.0 +/- 1.3 vs. 0.6
      +/- 0.3). CONCLUSIONS: Increased levels of GST-pi expression after chemotherapy
      are linked to drug resistance in patients with ovarian carcinoma.

PMID- 9028364
TI  - Evaluation of a nomogram used to predict the pathologic stage of clinically
      localized prostate carcinoma.
AB  - BACKGROUND: A Nomogram based on pretreatment prostate specific antigen (PSA)
      level, tumor grade, and clinical stage has recently been developed and
      distributed to physicians. It was distributed to aid physicians in making
      treatment recommendations by predicting the probability of the final pathologic
      stage of clinically localized prostate carcinoma. The Nomogram was based on data
      for one patient population, and the validity of its application in general
      urologic practices had not yet been evaluated. METHODS: In the current study, the
      authors tested the performance of the Nomogram against data from their series of
      697 men who underwent radical prostatectomy during the PSA era. Predictions made
      with the Nomogram were applied to the authors' data set, and the predictions were
      compared with actual outcomes of the authors' patients. A localized least-squares
      regression smoothing technique was used to determine whether the Nomogram was
      calibrated accurately for the authors' data and whether it discriminated across a
      full spectrum of patient characteristics. RESULTS: Many of the predicted
      probabilities of the Nomogram were accurate, but some were suboptimal when
      applied to the authors' data set. Although the Nomogram did discriminate quite
      well between organ-confined and nonconfined cancer, it had difficulty predicting
      high probabilities of seminal vesicle invasion and lymph node metastasis, which
      are the pathologic features with the most profound impact on prognosis.
      CONCLUSIONS: The Nomogram predicted organ-confined disease accurately. However,
      because not all of its predictions were completely calibrated when applied to the
      authors' data set, the authors conclude that the Nomogram may not be totally
      applicable to general urologic practice until further validation and possible
      modifications are performed.

PMID- 9028365
TI  - Erectile functioning of men treated for prostate carcinoma.
AB  - BACKGROUND: Published reports of complication rates, such as erectile
      dysfunction, associated with treatments for prostate carcinoma are often used to
      guide patient decision-making and develop clinical guidelines. Unfortunately, the
      published data are largely comprised of case series from single institutions.
      Meta-analysis is a methodology for combining findings from several studies to
      produce a better result. METHODS: A comprehensive literature review and
      subsequent meta-analysis of the rates of erectile dysfunction associated with
      external beam radiotherapy and radical prostatectomy was conducted. A simple
      logistic regression model was used to combine the data from 40 articles that met
      selection criteria. RESULTS: The probability of maintaining erectile functioning
      after radiotherapy is 0.69. The probability after surgery is 0.42. This
      difference is significant. Analysis of the effects of variables such as patient
      age and stage of disease on erectile functioning could not be performed due to
      inconsistencies across studies and the limited number of studies reporting such
      variables. CONCLUSIONS: The published data indicate that men with normal erectile
      functioning are more likely to retain this function after radiotherapy than after
      surgery. Attention is drawn to the weaknesses in the reviewed studies in the hope
      that the clinical trials of emerging treatments, such as cryotherapy,
      brachytherapy, three-dimensional conformal radiotherapy, and neoadjuvant hormones
      can be strengthened to reflect more accurately the rate of treatment-associated
      erectile dysfunction.

PMID- 9028366
TI  - Bone fractures associated with luteinizing hormone-releasing hormone agonists
      used in the treatment of prostate carcinoma.
AB  - BACKGROUND: Luteinizing hormone-releasing hormone agonists (LHRH-a) have become
      an established treatment for certain patients with prostate carcinoma. LHRH-a are
      known to decrease bone mineral density. The purpose of this study was to
      determine the risk of bone fracture in men receiving LHRH-a for prostate
      carcinoma. METHODS: A retrospective chart review and phone interviews were
      conducted to determine the incidence of bone fractures occurring in patients
      receiving LHRH-a for the treatment of prostate carcinoma. Abstracted data
      included the number of monthly LHRH-a injections, age, clinical stage of disease,
      sites of metastases, and bone fracture history. RESULTS: Twenty of the 224
      patients (9%) treated with LHRH-a for prostate carcinoma between 1988 and 1995 at
      3 teaching hospitals had at least 1 bone fracture during treatment with LHRH-a.
      The duration of treatment to the time of fracture ranged from 1 to 96 months
      (mean, 22.2 months). Seven fractures (32%) were osteoporotic in nature (i.e.,
      vertebral compression fractures or hip fractures after a fall from standing),
      whereas 8 fractures (36%) were associated with a significant traumatic event
      (i.e., a motor vehicle accident, boxing, etc.) and 5 were of mixed etiology. Two
      of 22 fractures (9%) were pathologic. CONCLUSIONS: This study demonstrated a 9%
      fracture incidence in a cohort of patients receiving LHRH-a for prostate
      carcinoma for up to 96 months. The incidence of osteoporotic fractures was 5%.

PMID- 9028367
TI  - Stereotactic radiosurgery for the treatment of brain metastases. Results of a
      single institution series.
AB  - BACKGROUND: Stereotactic radiosurgery is being used with increasing frequency for
      the treatment of brain metastases. Optimal patient selection and treatment
      factors continue to be defined. This study provides outcome data from a single
      institutional experience with radiosurgery and identifies parameters that may be
      useful for the proper selection and treatment of patients. METHODS: Eighty-four
      patients underwent stereotactic radiosurgery for brain metastases between
      September 1989 and November 1995. Seventy-nine patients (93%) were treated at
      recurrence after previous whole brain radiotherapy. Patients had between 1 and 6
      lesions treated with a median minimum tumor dose of 1600 centigrays (cGy). Thirty
      eight patients (45%) had active extracranial disease at the time of radiosurgery.
      RESULTS: Median survival for the entire group was 43 weeks from the date of
      radiosurgery and 71 weeks from the original diagnosis of brain metastases.
      Patients with 1 or 2 metastases had significantly improved survival compared with
      patients with > or = 3 metastases (P = 0.02), and patients without active
      extracranial tumor survived longer than those with extracranial disease (P =
      0.03). Median time to failure for 145 evaluable lesions was 35 weeks. Local
      control was significantly improved for radiosurgery doses of > 1800 cGy, and for
      melanoma histology. CONCLUSIONS: These results are comparable to reports of
      patients treated with resection and significantly superior to results observed
      after whole brain radiotherapy. The authors conclude that stereotactic
      radiosurgery is an effective, low risk treatment for extending the survival of
      patients with recurrent brain metastasis. Although survival is best for patients
      with < or = two lesions and no active extracranial disease, selected patients
      with > two lesions or active extracranial tumor may benefit as well.

PMID- 9028368
TI  - Spontaneous regression of primary intracranial germinoma. A case report.
AB  - BACKGROUND: Testicular seminomas are well known to regress spontaneously at a
      higher incidence than other tumors. To date, there have been no reports of
      spontaneous regression of an intracranial germinoma, although these tumors are
      histologically identical to testicular seminomas. METHODS: The authors present a
      patient with a primary intracranial germinoma that regressed spontaneously.
      RESULTS: A 21-year-old man was admitted to the study facility with acute onset of
      headache and vomiting. He had a 3-year history of polydipsia and polyuria.
      Computed tomography (CT) demonstrated a large tumor in the third ventricle,
      accompanied by hydrocephalus. He underwent ventriculoperitoneal shunt placement
      on the second day of hospitalization. A CT scan obtained on the fifth
      postoperative day demonstrated a remarkable decrease in tumor size. Because
      serial magnetic resonance imaging (MRI) demonstrated a gradual decrease in tumor
      size, tumor resection was not performed at that time. The patient was discharged
      and followed with MRI. The tumor continued to regress for more than 2 months. The
      patient was readmitted due to tumor regrowth, confirmed by MRI 4 months after the
      initial admission, despite the absence of symptom exacerbation. Two weeks later,
      the suprasellar portion of the tumor was resected through a right frontotemporal
      craniotomy. The histopathologic diagnosis was a germinoma. No concurrent tumors
      were found on whole body examination. The residual tumor gradually regressed
      after conventional radiation therapy and there has been neither tumor recurrence
      nor metastasis to date. CONCLUSIONS: Although the precise cause of the transient
      partial regression is unknown, this case indicates that, like their testicular
      counterparts, intracranial germinomas may on occasion spontaneously regress.

PMID- 9028369
TI  - Prognostic factors for thyroid carcinoma. A population-based study of 15,698
      cases from the Surveillance, Epidemiology and End Results (SEER) program 1973
      1991.
AB  - BACKGROUND: A number of prognostic factors for thyroid carcinoma have been
      identified, including sociodemographic characteristics, such as age and gender,
      and tumor characteristics, such as histology and stage. The relative importance
      of these factors as independent predictors of survival for patients with
      papillary, follicular, anaplastic, and medullary thyroid carcinoma has been
      extensively studied but remains uncertain. METHODS: The authors used data
      collected by the Surveillance, Epidemiology and End Results (SEER) program of the
      National Cancer Institute between 1973 and 1991 to investigate prognostic factors
      for each of the major histologic types of thyroid carcinoma in a population-based
      patient series and to assess the effect of these factors as predictors of
      survival. RESULTS: Both tumor and sociodemographic characteristics were
      independently associated with survival. Patients with papillary carcinoma had the
      highest 10-year relative survival (0.98), followed by those with follicular
      carcinoma (0.92) and medullary carcinoma (0.80). Anaplastic tumors had the lowest
      10-year relative survival (0.13). Stage at diagnosis and differentiation status
      were strong independent prognostic factors for each histologic type. Advanced
      stage at diagnosis was a stronger prognostic factor for medullary carcinoma than
      for other histologic types. Increasing age was associated with lower relative
      survival for each histologic type. Gender, marital status, and ethnicity were
      significant, but weaker, predictors of survival. CONCLUSIONS: Survival varied
      markedly among patients with different histologic types of thyroid carcinoma.
      Stage at diagnosis and tumor differentiation were important prognostic factors
      for each histologic type. Age at diagnosis was a stronger predictor of survival
      for patients with follicular and medullary carcinoma than for patients with
      papillary carcinoma.

PMID- 9028370
TI  - Metastasis to the thyroid gland. A report of 43 cases.
AB  - BACKGROUND: The incidence of metastasis to the thyroid gland in autopsy series
      varies from 1.25% to 24%. Metastasis to the thyroid gland is usually considered a
      terminal event, and the effectiveness of conventional treatment has been
      questioned. The authors assessed the effects of current methods of diagnosis and
      treatment on the course of the disease. METHODS: Forty-three patients with
      metastasis to the thyroid gland were studied retrospectively. Primary tumor
      origin was identified in all but two cases. Metastasis to the thyroid gland was
      confirmed by fine-needle aspiration cytology or histology. Data were analyzed for
      the frequency and types of malignant lesions, the clinical course of disease, and
      the prognosis after thyroid involvement. RESULTS: The kidney was the most common
      primary tumor site (33%), followed by lung (16%), breast (16%), esophagus (9%),
      and uterus (7%). The time from diagnosis of the primary tumor to metastasis to
      the thyroid gland was considerable for renal cell adenocarcinoma (mean, 106
      months) and for adenocarcinomas of the breast (mean, 131 months) and uterus
      (mean, 132 months). In 12 patients, this interval was more than 120 months. Fine
      needle aspiration cytology detected metastatic malignancy in 29 of 30 patients.
      Treatment involved surgery alone, surgery with adjuvant therapy, or nonsurgical
      methods. Two patients with uterine adenocarcinoma and one with breast
      adenocarcinoma had disease regression with no evidence of tumor recurrence.
      CONCLUSIONS: In any patient with a previous history of malignancy, no matter how
      remote that history is, a new thyroid mass should be considered recurrent
      malignancy until proved otherwise. Although detection of metastasis to the
      thyroid gland often indicates poor prognosis, aggressive surgical and medical
      therapy may be effective in a small percentage of patients.

PMID- 9028371
TI  - Primary smooth muscle tumors of the thyroid gland.
AB  - BACKGROUND: Primary smooth muscle tumors of the thyroid gland are rare. To date,
      there are few cases reported of primary thyroid leiomyomas and leiomyosarcomas.
      METHODS: One leiomyoma and four leiomyosarcomas arising within the thyroid gland
      were identified in the files of the Endocrine Tumor Registry of the Armed Forces
      Institute of Pathology. Histologic and immunohistochemical features were reviewed
      and follow-up obtained. RESULTS: The patients included 2 females, ages 56 and 64
      years, and 3 males, ages 45, 68, and 83 years. The patients presented with a mass
      in the thyroid gland that had increased in size over a number of months. All the
      tumors originated within a single lobe of the thyroid gland and measured from 1.1
      to 9 cm in greatest dimension. Histologically, there was a fascicular pattern of
      growth comprised of spindle-shaped cells with blunt-ended nuclei. The leiomyoma
      was encapsulated, cytologically bland, and amitotic; the leiomyosarcomas were
      invasive with increased cellularity, pleomorphism, a high mitotic rate, necrosis,
      and hemorrhage. Immunohistochemical staining showed reactivity with vimentin,
      smooth muscle actin, muscle specific actin, and desmin. The patient with the
      leiomyoma was alive without evidence of disease 11 years after the initial
      presentation, with surgical resection as the only treatment. Three of the
      patients with leiomyosarcomas were dead within 2 years of diagnosis, in spite of
      aggressive therapeutic intervention. The remaining patient was still alive 10
      months after initial presentation with multiple lung metastases. CONCLUSIONS:
      Smooth muscle tumors of the thyroid gland are distinctive tumors. Leiomyosarcomas
      can be distinguished from anaplastic carcinoma, although patient outcome is
      uniformly unfavorable.

PMID- 9028372
TI  - Phase II study of induction and adjuvant chemotherapy for squamous cell carcinoma
      of the head and neck. A long-term analysis for the Illinois Cancer Center.
AB  - BACKGROUND: In 1982, the Illinois Cancer Center initiated a Phase II trial in
      which the following treatment was administered: Induction chemotherapy (cisplatin
      and infusional 5-fluorouracil [5-FU]) was administered before definitive local
      therapy. Definitive local therapy, consisting of surgery, radiation, or both, was
      followed by three cycles of the same chemotherapy program. METHODS: Eligible
      patients had Stage III or IV squamous cell carcinoma of the head and neck with no
      distant metastases. Three cycles of induction chemotherapy were given. Cisplatin,
      100 mg/m2, was infused over 60 minutes on Day 1; thereafter, 5-FU (1000
      mg/m2/day) was given continuously for 5 days. Cycles were repeated at 3-week
      intervals. Local therapy was individualized, according to tumor stage and site.
      Patients who responded were to receive an additional three cycles of chemotherapy
      after surgery or radiation. RESULTS: Eighty-one patients were entered into the
      trial, and 71 were considered both eligible and evaluable. After induction
      chemotherapy, 59 patients (83%) responded, 23 of whom experienced complete
      response. Sixty-nine patients completed definitive local treatment, but only 22
      proceeded to the planned adjuvant cycles of treatment. Median follow-up of
      surviving patients was 12 years. At last follow-up, 13 patients were alive and
      free of malignancy, 9 of whom never had disease recurrence or a second primary
      tumor. These 13 patients had an acceptable quality of life, were ambulating, and
      were fully capable of caring for themselves. Overall, nine patients had second
      primary malignancies. Thirty-four percent of patients were alive at 5 years, and
      21% were alive at 10 years. Of 58 deaths, 44 resulted from progressive disease
      and 8 resulted from second primary cancers. Four patients died of unrelated
      causes, and two suffered lethal acute toxicity from the chemotherapy program.
      Late toxicity was moderate. Among 23 patients surviving at least 6 years, there
      were 3 cases of hypothyroidism, presumed to be secondary to radiation. Xerostomia
      was modest, consistent with usual radiation effects. Of the 13 patients who were
      alive and free of malignancy at last follow-up, none had clinical manifestations
      of serious late end organ toxicity. CONCLUSIONS: During long term follow-up after
      multimodal treatment of locally advanced squamous cell carcinoma, no obvious
      benefit was observed from the chemotherapy component of the treatment regimens
      rendered. Only 21% of patients achieved 10-year survival with the following
      causes of failure, in descending order of frequency: disease recurrence, second
      malignancies, other medical problems, and treatment-related deaths. The results
      of this trial are consistent with the results of other induction chemotherapy
      trials, indicating the need for innovative treatment strategies. These data do
      not support the continued use of induction chemotherapy with the cisplatin and
      infusional 5-FU program.

PMID- 9028373
TI  - Human papillomavirus (HPV) in head and neck cancer. An association of HPV 16 with
      squamous cell carcinoma of Waldeyer's tonsillar ring.
AB  - BACKGROUND: Certain strains of human papillomavirus (HPV) have been shown to be
      etiologically related to the development of uterine cervical and other genital
      cancers, but their role in the development of malignancies at other sites is less
      well established. Previous studies have shown HPV DNA in tumors of the head and
      neck, but its prevalence has varied depending on the detection methods and the
      types of tumor and/or tissue examined. This study was undertaken to estimate the
      frequency of HPV DNA in squamous cell carcinoma (SCC) at different sites of the
      esophagus, head and neck and to compare the clinical behavior of HPV positive and
      negative tumors. METHODS: DNA was extracted from frozen tissue of 167 SCCs of the
      esophagus, head and neck. The DNA was screened for HPV sequences by polymerase
      chain reaction with two sets of consensus primers, one to a conserved region in
      the L1 gene (MY09/ MY11) and the other to a conserved region in the E1 open
      reading frame (IU/IWDO). The products were run on agarose gels, detected by
      ethidium bromide staining, and then the gels were subjected to Southern blot
      analysis and hybridized with probes specific to HPV 6, 16, and 18. All tumors
      found to be HPV positive with the consensus primers were amplified with type
      specific primers, and in selected cases the presence of HPV DNA was confirmed by
      restriction enzyme digestion of the tumor DNA with conventional Southern blot
      analysis. RESULTS: Overall, HPV sequences were found in 25 of 167 tumors (15%),
      but HPV was detected most frequently in tumors in Waldeyer's tonsillar ring. In
      that area, 9 of 15 (60%) were HPV positive. No HPV DNA was detected in 11
      esophageal SCCs, 7 tumors of the pharynx/hypopharynx, or 6 pyriform sinus
      carcinomas. HPV DNA was detected in the following tumor sites: 1 of 28 (3.6%) in
      the larynx, 1 of 10 (10%) in the oral cavity, 5 of 39 (12.8%) in the tongue, 2 of
      15 (13.5%) in the floor of the mouth, 3 of 21 (14.3%) supraglottic, and 1 of 7
      (14.3%) in the lip. A high incidence of HPV DNA was also found in metastatic
      tumors located in cervical lymph nodes for which no primary site was clinically
      identified (3 of 8, 37.5%). With respect to age, gender, and tobacco and alcohol
      consumption, analysis of clinical data obtained by retrospective review showed no
      difference between patients with HPV DNA in their tumors and those in which no
      HPV was detected. However, HPV positive patients had larger tumors (P = 0.09) and
      a higher incidence of lymph node metastasis (P = 0.003). In spite of the higher
      stage of disease at presentation in HPV positive patients, there was no
      significant difference in 3-year survival rates between HPV positive patients and
      HPV negative patients (43.1% vs. 48.8%, respectively). Median follow-up was 27
      months. CONCLUSIONS: In the head and neck, HPV-associated SCC had site
      specificity with the viral DNA frequently found in tumors in Waldeyer's tonsillar
      ring. Patients with HPV positive tumors presented with a higher stage of disease
      than patients with HPV negative tumors, but there was no significant difference
      in the 3-year survival rates between these two groups of patients.

PMID- 9028374
TI  - Regression of metastatic carcinoid tumor after valvular surgery for carcinoid
      heart disease.
AB  - BACKGROUND: The carcinoid syndrome is a common sequela in patients with carcinoid
      tumor metastatic to the liver. Cardiac involvement occurs in 19-56% of patients
      with symptomatic carcinoid syndrome and, in some patients, leads to valvular
      surgery to relieve symptoms due to progressive right-sided heart failure. Reports
      of these patients have emphasized amelioration of cardiac symptoms, but
      postoperative tumor status rarely has been discussed. METHODS: This report
      describes four patients who underwent valvular heart surgery for severe carcinoid
      heart disease and had regression of their metastatic carcinoid tumor
      postoperatively. RESULTS: All four patients had definite clinical improvement in
      cardiac function and relief of symptoms related to congestive heart failure
      postoperatively. Unexpectedly, they also had regression of their metastatic
      disease, as reflected in decreased levels of urinary 5-hydroxyindoleacetic acid,
      and objective evidence of a reduction in the size of hepatic metastases.
      CONCLUSIONS: To the authors' knowledge, these four patients represent the first
      reported cases of metastatic disease regression after valvular surgery for
      carcinoid heart disease. Further descriptions of tumor status in patients having
      undergone a heart operation for this disease would be valuable in determining the
      clinical significance of this finding.

PMID- 9028375
TI  - Mixed connective tissue disease and radiation toxicity. A case report.
AB  - BACKGROUND: Several cases of long term radiation sequelae have been reported in
      patients with lupus erythematosus and systemic sclerosis after breast or chest
      wall irradiation. To the authors' knowledge, no experience with such
      complications in patients with mixed connective tissue disease (MCTD) has been
      reported previously. METHODS: A case of a woman with occult breast carcinoma
      metastatic to the axilla and preexisting MCTD is presented. To the authors'
      knowledge, this is the first case report of the adverse effects of breast
      irradiation in a patient with MCTD. The pathophysiology of such radiation injury
      to specific anatomic structures and technical dosimetric considerations of the
      radiation therapy and radiation dose are analyzed. The relevant literature on
      other collagen vascular diseases with features related to MCTD is reviewed.
      RESULTS: A moderate dose of radiation to the breast and regional lymphatics
      resulted in marked early and late toxicity to skin and subcutaneous tissues. The
      tissue injury was similar to that observed in patients with lupus erythematosus
      and systemic sclerosis. The early skin reaction (moist desquamation) was related
      to the daily radiation dose delivered at the depth of the epidermis, and the late
      reaction (subcutaneous fibrosis) was related to the dose at the depth of the
      dermal capillaries and dermal connective tissue. CONCLUSIONS: Patients with MCTD
      may develop exaggerated radiation reactions similar to those in patients with
      lupus erythematosus and systemic sclerosis. Although the incidence of such
      radiation reactions in patients with MCTD is difficult to assess, the risks and
      benefits of radiation therapy should be carefully weighed in these patients,
      particularly if an alternative therapy is available. If there is no alternative,
      judicious attention to radiotherapy technique may reduce or prevent skin
      toxicity.

PMID- 9028376
TI  - World Conference for Cancer Organisations. March 3-7, 1996, Melbourne, Australia.

PMID- 9028377
TI  - The management of pancreatic carcinoma ...a continuing challenge: introduction.

PMID- 9028378
TI  - Benefits versus risks from mammography. A critical reassessment.

PMID- 9028379
TI  - Managed health care: an overview.

PMID- 9028380
TI  - Role of professional organizations and managed health care.

PMID- 9028381
TI  - The government and managed health care.

PMID- 9028382
TI  - The American Cancer Society and Mission 2000.

PMID- 9028383
TI  - Managed care: the future.

PMID- 9028384
TI  - Insulin-like growth factor I receptor messenger RNA in the colon is unchanged
      during neoplasia.
AB  - The expression of growth factor receptor messenger RNA is difficult to quantitate
      due to low copy number. We describe a quantitative polymerase chain reaction that
      rapidly, reproducibly assays expression of human insulin-like growth factor I
      (IGF-I) receptor mRNA from small, biopsy-sized, specimens of tissue. This was
      then clinically applied to surgically resected specimens of colon. Total RNA was
      isolated from normal colonic mucosa and documented tumors from 4 patients
      undergoing resection. The mRNA was first reverse-transcribed with an oligomer
      bearing a complementary sequence specific for the mRNA at its 3' end, and a
      sequence complementary to an intervening intron of the IGF-I receptor gene at the
      5' end. Competitive PCR was then performed in the presence of the cDNA product
      and exogenously added genomic DNA, with an upstream primer complementary to the
      exon sequence of the gene of interest and a downstream primer complementary to
      the intron sequence that was tagged to the cDNA. The genomic DNA was used as the
      internal standard. To calculate the number of copies of mRNA per microgram total
      RNA, a standard curve was used. No difference was noted in IGF-I receptor
      expression between neoplastic and normal colonic mucosa. This quantitative PCR is
      accurate, rapid, and requires very small amounts of tissue. Potential uses are in
      determining genetic expression of growth factor receptors or putative tumor
      markers preoperatively from small samples obtained during diagnostic colonoscopy
      or from samples obtained at surgery.

PMID- 9028385
TI  - Hormone dependence of mammary tumors induced in rats by intraperitoneal NMU
      injection.
AB  - The purpose of this work was to determine the hormone dependence of mammary
      tumors induced in Sprague-Dawley rats by three intraperitoneal injections of N
      nitroso-N-methylurea at 50, 80, and 110 days of age. Two experimental designs
      were carried out: (a) Ten days before the first NMU injection, 130 rats were
      divided into 13 batches and randomly assigned to the following treatments:
      control, ovariectomy (OVX), tamoxifen (TAM), bromocriptine (BROM), haloperidol
      (HAL), estradiol (E2), progesterone (Pg), OVX + BROM, TAM + BROM, OVX + HAL, TAM
      + HAL, OVX + TAM, and E2 + BROM. After 150 days of treatment the following growth
      parameters were determined: latency period (LP), mean tumor number per rat (n/t),
      and tumor incidence (TI). LP was significantly increased (p < 0.05) only by Pg
      and TAM + BROM. The n/t was significantly decreased (p < 0.05) by all treatments
      except HAL. TI was significantly reduced by OVX, TAM, BROM, and their
      combinations, (b) Rats bearing ip-NMU-induced mammary tumors were divided into 7
      batches and assigned to the following treatments: control, OVX, TAM, BROM, HAL,
      OVX + BROM, and TAM + BROM. Tumor growth was assessed up to 60 days of treatment;
      only OVX, TAM and their combination with BROM were able to produce tumor
      regression. These results support the essential role of E2 and prolactin in the
      promotion stage of carcinogenesis. However, for established tumors, growth
      becomes more independent from hormone influence, in particular from prolactin
      deprivation. We conclude that this model seems suitable for studying the
      mechanisms underlying the evasion of hormonal control of tumor growth.

PMID- 9028386
TI  - Lipid-laden macrophage infiltration of human adenocarcinoma in vivo associated
      with taxol and GCSF treatment.
AB  - This brief report illustrates the presence of lipid-laden macrophages in
      proximity to metastatic adenocarcinoma cells within the bone marrow of a patient
      receiving taxol and GCSF therapy. The pathophysiological mechanism is uncertain.
      Taxol, which is associated with macrophage function in vitro, may have been
      responsible for the recruitment of macrophages in this patient. GCSF could have
      contributed as well; however, GCSF usually has little effect on monocytes and
      macrophages.

PMID- 9028387
TI  - Hemostatic defects in cancer patients.

PMID- 9028388
TI  - Controversies in the antibacterial treatment of patients with neutropenia: a
      matter of comprehension or apprehension?

PMID- 9028389
TI  - Is TNF really involved in cachexia?
AB  - A review on the possible involvement of tumor necrosis factor-alpha (TNF) in
      cachexia is presented. While this cytokine is definitely linked to sepsis and
      tumor-associated weight loss in some experimental models, other cytokines, such
      as interleukin-6 (IL-6) or interferon-gamma (IFN-gamma), alone or in combination
      with TNF, may also play an important role in the development of cachexia.

PMID- 9028391
TI  - Multiple myeloma: prognosis and standard treatment.

PMID- 9028392
TI  - Bone marrow transplantation in multiple myeloma.

PMID- 9028393
TI  - The biological features of multiple myeloma.

PMID- 9028394
TI  - Pathophysiology and management of bone disease in multiple myeloma.

PMID- 9028404
TI  - Important, but neglected: the health of young women in a tropical environment.

PMID- 9028405
TI  - Do young women in tropical regions constitute a recognized social category?
AB  - In most tropical regions there is little organized health care for young women,
      yet their household roles within contexts of worsening socio-economic situations
      create special health problems. In the area of sexual and reproductive health,
      the onset of reproductive roles does not entitle the young women to either
      maternal and child health services or family planning services unless they are
      married and have children under 5 years. Societal values and norms at macro and
      micro levels have prevented young women from benefiting from reproductive
      technology, although they are, at the same time, increasingly expected to spend a
      great deal of their youth in school and outside marriage. Young women thus live
      in paradoxical situations as indicated by the increasing levels of early teenage
      pregnancy, induced abortion and related complications, school drop-out and
      infection with sexually transmitted diseases including HIV/AIDS. Young women
      clearly constitute an unrecognized social category, and research focusing on them
      would be particularly rewarding because of the potential it offers for addressing
      the gender imbalances and their dynamics in health.

PMID- 9028406
TI  - Providing accessible health care for adolescents with sexually transmitted
      disease.
AB  - Provision of sexually transmitted disease (STD) care for sexually active
      adolescents has been neglected in developing countries, although this is
      changing. Available evidence indicates that STDs are a serious problem among
      adolescents (10-19 years), especially in rural areas where services are limited
      for any age group. Curative care is hampered by the inadequacy of the syndromic
      approach for identifying adolescents with asymptomatic infections, especially
      Chlamydia trachomatis. There is an urgent need to asses STD interventions for
      adolescents in controlled studies, with numbers and follow-up sufficient to
      monitor changes in STD markers. Many programmes report increased uptake of
      condoms by youth but have been unable to demonstrate its effect on STD/HIV rates.
      It is unlikely that any one approach to adolescent STD services will be feasible
      and hence the importance of understanding the benefits and limitations of each
      approach.

PMID- 9028407
TI  - The problem of post-partum fistulas in developing countries.
AB  - Postpartum fistulas are frequent in the tropical environment. They are mostly
      found in very young women who live in remote areas. Without treatment women with
      fistulas will be condemned to the disconsolate life of social outcasts. Good
      operative treatment is crucial. The different operative methods are discussed.
      The operation through vaginal approach can be performed in any hospital. It does
      not need special surgical skill. More important than surgery is prevention of
      postpartum fistulas through a well-organised primary health care program which
      reaches out into the villages and which includes adequate prenatal controls and
      competent midwifery.

PMID- 9028408
TI  - Schistosomiasis in women: manifestations in the upper reproductive tract.
AB  - Female genital schistosomiasis (FGS) is a neglected disease entity which may give
      rise to considerable suffering among women of child-bearing age in areas where
      schistosomiasis (especially due to Schistosoma haematobium) is prevalent. The
      close relation between the vessels in genital organs and the urinary bladder
      enables the parasite to easily change location to virtually any organs in the
      female pelvic area. Symptoms concur with the anatomical location of worm pairs
      and their ova. Lesions of the lower female genital tract can easily be
      investigated by cytology, histology or direct demonstration of eggs in scrapings
      or biopsies whereas schistosomiasis of the upper genital tract is clinically
      indecipherable and less accessible for examination. In the literature there are
      references to FGS as a cause of infertility, complications of pregnancy,
      menstrual disorders, problems related to sexual intercourse, diagnostic
      similarities to STDs and cancer, unspecified complaints related to blood loss,
      chronic abdominal pain, social segregation and related psychological problems.
      The diagnosis of female upper genital schistosomiasis is difficult and the
      authors point out possible diagnostic procedures which might be helpful for
      further understanding of this complex entity.

PMID- 9028409
TI  - Female genital schistosomiasis due to Schistosoma haematobium. Clinical and
      parasitological findings in women in rural Malawi.
AB  - A total of 51 women with urinary schistosomiasis haematobium were examined in
      order to identify diagnostic indicators for female genital schistosomiasis (FGS).
      Patients were selected at random from the outpatient department of the Mangochi
      District Hospital, Malawi. The medical histories were recorded according to a pre
      designed questionnaire and the women were subjected to a thorough gynaecological
      examination including colposcopy and photographic documentation of lesions.
      Microscopy of genital biopsies revealed that 33 of the 51 women had S.
      haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova
      in urine. The most sensitive diagnostic procedure was beside microscopic
      examination of a wet cervix biopsy crushed between two glass slides, which
      revealed 25 of the 33 genital infections. There was a significant correlation
      between the size of genital lesions and the number of ova counted per mm2 of
      crushed tissue. Women with FGS had significantly more tumours in the vulva than
      women with schistosomiasis limited to the urinary tract. Most of the observed
      genital pathology could easily be identified by the naked eye, but colposcopic
      examination yielded valuable additional information like the demonstration of
      neovascularisation around cervical sandy patches. Few of the symptoms previously
      regarded as indicators for FGS could be linked to the presence of schistosome ova
      in genital tissue. Husbands of infertile women with FGS had children with other
      women significantly more often than husbands of women who only had urinary
      schistosomiasis. This, together with the finding that the majority of the
      divorced women had FGS, indicates that the manifestation of this disease may have
      implications for the marital and sexual life of the affected women.

PMID- 9028410
TI  - Female genital schistosomiasis (FGS): relationship between gynecological and
      histopathological findings.
AB  - Schistosomiasis of the lower female reproductive tract manifests itself in a
      broad spectrum of clinical features. However, clinical and histopathological
      findings have never been studied in a synoptic manner. Based on the assumption
      that any type of pathology present in the female reproductive tract is the
      expression of a complex pathophysiological reaction towards eggs sequestered in
      the genital tissues, we decided to analyze colposcopic and histopathological
      findings in a comprehensive manner. Thirty-three women in Malawi with urinary and
      genital schistosomiasis were examined parasitologically and gynecologically. A
      thorough colposcopic examination with photodocumentation was performed and
      biopsies were taken from the cervix, the vagina and/or the vulva for histological
      sectioning and immunohistochemistry. The predominant colposcopic findings were
      sandy patches on the cervical surface similar to those seen in the bladder and
      polypous/papillomatous tumors with irregular surface on the vaginal wall and in
      the vulvar area. The histopathological sections of sandy-patch-like lesions
      demonstrated only a small cellular reaction around S. haematobium eggs in various
      stages of disintegration. In contrast, in the case of polyps the histology
      revealed a more pronounced immunological reaction characterized by a heavy
      cellular infiltrate. One case of invasive squamous cell carcinoma of the cervix
      was diagnosed. We conclude that colposcopy is a useful tool in the detection of
      FGS related pathology in the lower female reproductive tract and that the
      synoptic assessment of surface and of corresponding histological sections helped
      to understand the pathophysiology of S. haematobium associated disease in genital
      tissue.

PMID- 9028411
TI  - Diagnosis of female genital schistosomiasis by indirect disease markers:
      determination of eosinophil cationic protein, neopterin and IgA in vaginal fluid
      and swab eluates.
AB  - Based on assumptions about the pathophysiology of egg-related lesions in the
      lower reproductive tract, putative indirect disease markers were investigated in
      vaginal fluids from 54 Malawi adolescent girls and women infected with S.
      haematobium. These women received a careful gynecological examination during
      which biopsies were taken from the cervix, and, if present, also from suspicious
      lesions in the vagina and the vulva. If the biopsies, either in wet crushed
      preparations or in histological sections, contained eggs the patients were
      considered to have female genital schistosomiasis (FGS; n = 33). The remainder (n
      = 21) were classified as having urinary schistosomiasis only. Eosinophil cationic
      protein (ECP), a cytotoxic granule protein of eosinophils, neopterin, a second
      messenger molecule generated during the activation of macrophages, and IgA as an
      indicator of local B-cell activation were quantitatively determined in vaginal
      fluid. To clarify the origin of ECP, this protein was also looked for in
      histological sections by an immunohistochemical method. In order to explore
      whether such disease markers can be detected after absorption to a tampon-like
      material, ECP and IgA were also assessed after elution from a non-porous,
      polypropylene fibre web impregnated with vaginal fluid. The concentration of ECP
      in vaginal fluid and the degree of immunohistochemical staining in histological
      sections were significantly higher in patients with FGS than in women with
      urinary schistosomiasis only. The amount of ECP detected in histological sections
      correlated to the number of eggs/mm2 of compressed genital tissue (rho = 0.36, P
      = 0.02), and the concentration of ECP in vaginal fluid correlated to the
      concentration of neopterin as well as to that of IgA (rho = 0.52, P = 0.004 and
      rho = 0.37, P = 0.02, respectively). Median neopterin concentration in vaginal
      fluid was also higher in the FGS group, but the difference was not statistically
      significant. ECP could also be detected in eluates from impregnated fibre webs,
      but the concentration was approximately one power of 10 less than in the original
      vaginal fluid. These results demonstrate that indicators of immunological
      mechanisms related to the egg-granuloma might be useful as indirect disease
      markers for women with FGS if assessed in vaginal washings or swab eluates.

PMID- 9028412
TI  - Urine reagent strips for diagnosis of schistosomiasis haematobium in women of
      fertile age.
AB  - Hematuria, proteinuria and leukocyturia were semiquantitatively assessed by
      reagent strips in single morning urine of women of fertile age visiting the
      outpatient department of the Mangochi district hospital, Malawi. This was part of
      a diagnostic approach to female genital schistosomiasis (FGS). In 51 women ova of
      Schistosoma haematobium were detected in urine by a filtration technique. In 33
      of these women ova were also present in genital tissue as demonstrated by
      microscopic examination of biopsies. In 209 women no ova were found in the single
      urine filtered. There were significantly higher scores for hematuria, proteinuria
      and leukocyturia as well as of the combined reagent strip index (RSI) in egg
      excreting than in egg-negative women. The sensitivity of a single hematuria,
      proteinuria and leukocyturia reading was 98, 84 and 73%, respectively. However,
      the respective specificity was only 24, 22 and 23%. The best prediction of
      urinary schistosomiasis was achieved by a +2 score for hematuria, of which the
      sensitivity was 94% and the specificity was 61%. The high false-positive rates
      can probably be explained by contamination of urine by vaginal secretion.
      Moreover, cases of schistosomiasis have probably been overlooked because only a
      single morning urine sample was examined. The total absence of hematuria,
      proteinuria and leukocyturia, however, may be used to rule out heavy infections
      in community surveys. There was no difference in reagent strip scores between
      women with genital and urinary schistosomiasis as compared with those with
      urinary tract lesions alone. Thus urine analysis reagent strip readings do not
      help to discriminate between S. haematobium infected women with and without FGS.

PMID- 9028414
TI  - Intranasal antihistamine gains marketing approval.

PMID- 9028413
TI  - Reversibility of lower reproductive tract abnormalities in women with Schistosoma
      haematobium infection after treatment with praziquantel--an interim report.
AB  - Little is known whether and to what extent antiparasitic treatment cures female
      genital schistosomiasis (FGS). Using a standard protocol, of twenty-one women
      with FGS nine were re-examined at two to nine weeks after they had been treated
      with praziquantel at a single dose of 40 mg/kg. Symptoms related to pathology of
      the urinary tract and to a lesser extent of genital pathology subsided in most
      patients. Schistosoma haematobium ova were no longer detectable in urine of any
      of the patients post-treatment. Efficiency of chemotherapy against adult worms
      was confirmed by the disappearance of circulating anodic antigen (CAA) in serum.
      Sandy patches showed resolution in two of four cases after chemotherapy.
      Papillomata due to schistosomiasis alone improved, but persisted in mixed
      infection with human papilloma virus (HPV) or when HPV was the only underlying
      cause. In one patient ulcera could not be related with certainty to
      schistosomiasis at admission, but resolved after treatment with parziquantel.
      Leukoplakia (two cases) was not influenced by chemotherapy, or even increased
      during follow-up, regardless of whether ova had been detected or not. Although
      the follow-up period was rather short, time intervals were not standardized, and
      a relatively small number of patients was investigated, it could be shown that
      genital pathology due to sequestered S. haematobium ova is, at least partially,
      reversible already two to nine weeks after killing the adult worms by
      praziquantel. This is paralleled by a normalization of inflammatory immune
      responses detectable in histological sections and vaginal lavage.

PMID- 9028416
TI  - Recapping needles in the pharmacy.

PMID- 9028417
TI  - Patient-centered computing.

PMID- 9028418
TI  - Promoting use of angiotensin-converting-enzyme inhibitors.

PMID- 9028419
TI  - Trends in health information systems technology.
AB  - Major trends in health information systems technology are described. The new
      paradigm for information systems is integrated, patient-centered computing. The
      computer system and files are designed around information-capture needs along the
      continuum of care instead of around charge capture or inventory. The need for
      patient information in the future will not be limited to the health system but
      will extend to work sites and homes. Health systems will move to full client
      server architecture, higher-speed data transmission, and greater network
      capacity. Computing standards will be instituted nationwide. With changes in the
      economics of health care, physician order-entry systems are inevitable. Many
      health systems and system vendors are making progress in achieving the computer
      based patient record (CPR); health systems will require the CPR if they are to be
      truly integrated. Trends in health care and health care information technology
      will require that pharmacists innovate and adapt as never before.

PMID- 9028420
TI  - Health system informatics.
AB  - The application of informatics in a health system in general and to pharmacy in
      particular is discussed. Informatics is the use of information technology to
      enhance the quality of care, facilitate accountability, and assist in cost
      containment. Tying the pieces of health care into a seamless system using
      informatics principles yields a more rational approach to caregiving. A four
      layer hierarchy of information systems can be found in any health system: layer
      1, the foundational layer formed by a transaction-processing system; 2, the
      management information system; 3, decision support; and 4, advanced informatics
      applications such as expert systems. Other industries appear to be ahead of
      health care in investing in informatics applications. Pharmacy is one of the key
      health care professions that must adopt informatics. A stepwise structure for
      pharmacy informatics has been proposed; it consists of establishing a
      relationship with the patient, establishing a database, listing and ranking
      problems, choosing among alternatives, and planning and monitoring. Informatics
      should be approached by determining where the department is going strategically.
      Informatics standards will be needed. Pharmacists will need to use informatics to
      enhance their worth on the health care team and to improve patient care.

PMID- 9028421
TI  - Arden Syntax: the emerging standard language for representing medical knowledge
      in computer systems.
AB  - The Arden Syntax for Medical Logic Modules standard language for knowledge-based
      computer systems is described. Knowledge systems can use computerized patient
      data in decision-making. Although they have the potential to reduce adverse drug
      events and infection rates, improve drug dosing, and decrease the cost of care,
      knowledge systems have not yet reached the average patient. Arden Syntax for
      Medical Logic Modules is the standard language for defining clinical decision
      rules that drive alerts, reminders, clinical guidelines, and data
      interpretations. Each medical logic module (MLM) in an Arden Syntax knowledge
      base is designed to make one type of decision. MLMs usually represent either
      rules that can be encoded, such as generating a warning that the potassium
      concentration is decreasing in a patient taking digoxin, or complex decision
      trees for individual patient care plans and clinical protocols. An MLM contains
      maintenance slots (title, file name, version, originating institution, author,
      date, specialist, validation information), library slots (stating the MLM's
      purpose and providing keywords for searching), and knowledge slots (containing
      the "essence" of the MLM). Arden Syntax is receiving growing support from the
      medical and information systems communities as the standard language for medical
      knowledge systems, but legal, ethical, regulatory, and ownership issues remain.
      If pharmacy is to grow and prosper as a knowledge profession, it should adopt an
      accepted standard language for representing active, applied knowledge in computer
      systems.

PMID- 9028422
TI  - Mycophenolate mofetil: a unique immunosuppressive agent.
AB  - The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects,
      and dosage and administration of mycophenolate mofetil are reviewed.
      Mycophenolate mofetil is used to prevent or treat allograft rejection after solid
      organ transplantation. A prodrug, mycophenolate mofetil is rapidly hydrolyzed to
      mycophenolic acid after oral administration. Mycophenolic acid inhibits de novo
      purine synthesis, resulting in antiproliferative effects on T and B lymphocytes.
      The absolute bioavailability of mycophenolic acid is 94% for oral administration;
      the maximum plasma concentration occurs after two hours. Mycophenolic acid
      undergoes hepatic glucuronidation to an inactive salt that is renally excreted.
      Clinical trials of mycophenolate mofetil in renal transplant patients suggest
      that the drug is effective for the prevention of acute rejection and as rescue
      therapy. Clinical data on mycophenolate mofetil therapy in liver transplant
      patients are too limited to permit conclusions. Clinical trials of the drug for
      primary immunosuppression in heart transplant patients have not been conducted,
      but studies of this agent as rescue therapy suggest efficacy. Mycophenolic acid
      has proved useful for long-term management of psoriasis. The most common adverse
      effects of mycophenolate mofetil are gastrointestinal. Nephrotoxicity and overt
      hepatotoxicity have not been reported, but the drug may be linked to bone marrow
      suppression and certain malignancies. Mycophenolate mofetil is available as a 250
      mg capsule for oral use. The recommended initial dosage is 1 g twice daily.
      Mycophenolate mofetil appears to be a useful addition to the armamentarium of
      immunosuppressive drugs, particularly for kidney transplant patients, but more
      study is needed to clarify its role.

PMID- 9028423
TI  - Drug-related problems in emergency department patients.

PMID- 9028425
TI  - ASHP guidelines on the pharmacist's role in the development of clinical care
      plans.

PMID- 9028424
TI  - ASHP therapeutic guidelines on angiotensin-converting-enzyme inhibitors in
      patients with left ventricular dysfunction. This official ASHP practice standard
      was developed through the ASHP Commission on Therapeutics and approved by the
      ASHP Board of Directors on November 16, 1996.

PMID- 9028426
TI  - Albendazole monitoring.

PMID- 9028427
TI  - Hypoprothrombinemia induced by warfarin sodium and cisapride.

PMID- 9028428
TI  - Chromium as an industrial carcinogen: Part I.
AB  - Successive cohorts by year of hire at the same chromate plant (1931-1932, 1933
      1934, 1935-1937) and the combined cohort (1931-1937) of 332 employees were
      followed through 1993. A total of 283 deaths (85%) of the total cohort were
      identified. In the combined cohort (1931-1937), 66 lung cancers were found,
      constituting 23.3% of all deaths and 64.7% of all cancers. The lung cancer
      mortality rates are shown over a span of decades, from 15 years to over 55 years,
      with progressive rise. Observations of lung cancer identified, employees not
      found, and cancer risk by age at hire are cited. Lung cancer death rates
      increased by gradient level of exposure to insoluble (trivalent) chromium and to
      soluble (hexavalent) chromium, with a pattern of increase by total chromium. Age
      specific death rates for lung cancer according to the same gradient exposure
      range for total, insoluble, and soluble chromium are presented. The potential
      cancer risk extends to all forms of chromium and to total chromium.

PMID- 9028429
TI  - Chromium as an industrial carcinogen: Part II. Chromium in human tissues.
AB  - A continuation of the findings in a study of workers hired in 1931-1937 in a
      chromate plant, directed at the evaluation of the carcinogenic risk of insoluble,
      soluble, and total chromium. Chemical analyses of tissues of autopsies,
      identified by age at hire, cumulative exposure to insoluble, soluble, and total
      chromium and interval since last exposure are cited for three lung cancer cases.
      Histological identification of insoluble chromium was demonstrated. Marked
      deposition and retention of concentrations of chromium was noted 18.0 years since
      last exposure. In one case with cumulative exposure to insoluble chromium of
      10.74 mg versus 0.63 mg for soluble chromium and histological demonstration of
      insoluble chromium, chrysotile was also identified.

PMID- 9028430
TI  - Menstrual patterns of workers exposed to low levels of 2-ethoxyethylacetate
      (EGEEA).
AB  - The objectives of this study were to determine the exposure levels among workers
      who handle 2-ethoxyethylacetate (EGEEA) in the liquid crystal display (LCD)
      manufacturing industry and to study the menstrual patterns among the exposed
      workers compared to a referent group of workers. A total of 52 female exposed
      workers and 55 referents was studied. Detailed menstrual histories were obtained
      by personal interview using a structured questionnaire. All the exposed had
      individual 8-hour personal monitoring for EGEEA in the environment and start-of
      shift and end-of-shift urine analysis for EGEEA concentration. The geometric mean
      end-of-shift urine EGEEA concentration was 0.16 mg/g creatinine. End-of-shift
      urine EGEEA was well correlated with the air concentration; r = 0.81 [p <
      0.0001]. No significant differences were observed between the exposed and
      referent groups for duration of each menstrual cycle (period), duration (days) of
      the menses, and the amount of flow, even after adjusting for possible confounders
      viz. age, years of education, use of oral contraceptive pills, age at menarche,
      gravidity, and race. The workers in the LCD manufacturing industry were exposed
      to a mean TWA of 0.51 ppm of EGEEA. At this concentration, the findings did not
      reveal any significant difference between the menstrual patterns of the exposed
      and referent subjects.

PMID- 9028431
TI  - Sinonasal cancer and occupation. Results from the reanalysis of twelve case
      control studies.
AB  - A pooled reanalysis of twelve case-control studies on sinonasal cancer and
      occupation from seven countries was conducted in order to study associations with
      occupations other than wood- and leather-related occupations. The pooled data set
      included a total of 930 cases (680 men and 250 women) and 3,136 controls (2,349
      men and 787 women). All the studies included a detailed occupational history for
      cases and controls. Each job was coded using the same classifications for
      occupation and industry. Two approaches were used in the analysis: systematic
      analysis of occupations; a priori analysis using a preestablished list of
      occupations and industries. The results confirmed associations observed in
      several studies not included in this analysis. For agricultural workers,
      significant excesses were observed for squamous cell carcinoma among women (OR =
      1.69) and men (OR = 3.72 for ten years or more of employment as an orchard
      worker), and adenocarcinomas among men (OR = 2.98 for ten years or more of
      employment). Associations with textile occupations were observed for
      adenocarcinoma among women (OR = 2.60) and squamous cell carcinoma among men (OR
      = 5.09 for fiber preparers, 3.01 for bleachers). Elevated risks for both
      histologic types were observed among men employed in food manufacturing (OR =
      3.25, adenocarcinoma), or as food preservers (OR = 13.9, squamous cell
      carcinoma), and among men employed as cooks (OR = 1.99, squamous cell carcinoma).
      A positive association with squamous cell carcinoma was observed for male
      transport equipment operators (OR = 1.21), and also with adenocarcinoma for male
      motor-vehicle drivers (OR = 2.50). A number of other associations were observed
      in the systematic analysis.

PMID- 9028432
TI  - Occupational exposure to machining fluids and laryngeal cancer risk: contrasting
      results using two separate control groups.
AB  - This death certificate-based case-control study linked Connecticut Tumor Registry
      and Connecticut Division of Vital Statistics death data to determine whether
      machining fluid exposure is associated with laryngeal cancer risk. Laryngeal
      cancer cases were compared with oral cancer controls and general population
      controls. Level of exposure to machining fluids was imputed from the usual
      occupation and industry on the death certificate. Because exposure was infrequent
      among females, analysis was limited to males. When cases were compared to oral
      cancer controls, high exposure to machining fluids was associated with laryngeal
      cancer (odds ratio = 1.48; 95% confidence interval = 1.01-2.16), with a p-value
      for trend of 0.08. When cases were compared to population controls, no
      association between machining fluid exposure and laryngeal cancer was observed. A
      possible reason for the contrasting results, other than chance, is that exposure
      data quality for the cases and oral cancer controls may have differed from that
      of the population controls.

PMID- 9028433
TI  - Increased mortality from chronic liver disease and cirrhosis 13 years after the
      Taiwan "yucheng" ("oil disease") incident.
AB  - In 1979, a mass poisoning involving some 2,000 persons occurred in central Taiwan
      from cooking oil contaminated by polychlorinated biphenyls (PCBs) and their heat
      degraded byproducts, including polychlorinated dibenzofurans (PCDFs). The
      responsible health department registered cases for clinical purposes between 1979
      and 1983. The exposed persons are referred to as the "yucheng" (oil disease)
      cohort. PCBs and PCDFs are toxic chemicals widely dispersed in the environment
      and in human tissue, which persist long after exposure. The consequences of
      exposure to these agents are not well understood. We traced the cohort through
      December 31, 1991, and compared overall and cause-specific mortality of 1,837
      "yucheng" subjects with age, gender, and calendar time-specific mortality rates
      for the Taiwan general population. Eighty-three deaths were identified from
      23,404 observed person-years. Even though the overall standardized mortality
      ratio (SMR) was 0.8 (95% confidence interval (CI) 0.7-1.0), there was a
      substantial elevation in the mortality rate for chronic liver disease and
      cirrhosis (10 deaths, SMR = 2.7, 95% CI = 1.3-4.9). Mortality from malignant
      neoplasms and other causes was not significantly different from that of the
      Taiwan population. PCB/PCDF exposure appears to promote the development of severe
      liver disease, perhaps in combination with known risk factors such as infection
      with hepatitis B virus. Further follow-up of this young cohort is necessary to
      see if the consequences include hepatic cancer.

PMID- 9028434
TI  - Proportionate mortality among unionized construction ironworkers.
AB  - This report presents the results of proportionate mortality ratios (PMR) and
      proportionate cancer mortality ratios (PCMR) among 13,301 members of the
      International Union of Bridge, Structural, and Ornamental Ironworkers who had
      been members for a minimum of 1 year, were actively paying dues into the death
      beneficiary fund, and had died between 1984-1991. Using the United States
      proportionate mortality rates as the comparison population, statistically
      significant elevated risks, using 95% confidence intervals (CI), were observed
      for several types of injuries: falls (N = 259, PMR = 3.57, CI = 3.15-4.03),
      transportation injuries (N = 363, PMR = 1.22, CI = 1.10-1.35), and other types of
      injuries (N = 225, PMR = 1.63, CI = 1.43-1.86). The deaths due to falls were
      significantly elevated for each 10-year age group under age 60 (PMR > 7.00) and
      for those workers with < 20 years in the union (PMR > 6.00). Elevated mortality
      risks were also observed for all malignant neoplasms combined (N = 3,682, PMR =
      1.09, CI = 1.06-1.13) as well as for site-specific malignant neoplasms of the
      lung (N = 1,523, PMR = 1.28, CI = 1.21-1.35), pleural mesothelioma (N = 7, PMR =
      1.67, CI = 0.67-3.44) and "other and unspecified sites" (N = 307, PMR = 1.29, CI
      = 1.15-1.44). The category "pneumoconiosis and other respiratory diseases" was
      also significantly elevated (N = 690, PMR = 1.11, CI = 1.03-1.20); in this
      category, deaths due to asbestosis had the greatest elevated risk (N = 10, PMR =
      3.56, CI = 1.70-6.54). No elevation in risk was found for kidney cancer or for
      chronic nephritis which were of interest because of Ironworkers' potential
      exposure to lead. The present study underscores the importance of fall protection
      and other injury prevention efforts in the construction industry, as well as the
      need to control airborne exposures to asbestos, welding fumes and other
      respirable disease hazards.

PMID- 9028436
TI  - Exposure to potential occupational asthmogens: prevalence data from the National
      Occupational Exposure Survey.
AB  - Few data are available about the prevalence of occupational exposures to agents
      which can cause occupational asthma or aggravate preexisting asthma (asthmogens).
      Using potential occupational exposure data from the National Occupational
      Exposure Survey (NOES) of 1980-1983, we investigated the number of asthmogen
      exposures, asthmogen-exposure(s) per production worker, and unprotected
      occupational asthmogen exposures in different industries and occupations. Data
      for the entire United States were used to generate estimates of occupational
      exposure at two selected state and local levels. It was estimated that 7,864,000
      workers in the surveyed industries were potentially exposed to one or more
      occupational asthmogen(s) in the United States. The average number of observed
      potential exposures per asthmogen-exposed worker was 4.4, and varied from 11.9,
      in the Water Transportation industry, to 1.2 in Local and Suburban
      transportation. The largest number of observed potential exposures was recorded
      in the Apparel and Other Finished Products (garment) industry. This work and
      further analyses using this approach are expected to contribute to a better
      understanding of the epidemiology of occupational asthma, and to serve as a guide
      to target future occupational asthma surveillance efforts.

PMID- 9028435
TI  - Lead levels in Maryland construction workers.
AB  - A cross-sectional study of unionized construction workers not currently known to
      be performing lead work was conducted. Participants completed an interviewer
      administered questionnaire obtaining information about demographics, work
      history, other possible sources of lead exposure and health status (including
      hypertension, noise-induced hearing loss and renal disease). Blood was then
      obtained via venipuncture for whole blood lead level, hematocrit and free
      erythrocyte protoporphyrin determination. Two hundred and sixty-four Maryland
      construction workers had median whole blood lead determinations of 7
      micrograms/dl and mean values of 8.0 micrograms/dl, with a skewed distribution
      ranging from 2 to 30 micrograms/dl. None were currently engaged in known lead
      work. Blood lead levels were significantly higher for the 124 who had 'ever'
      worked in demolition (8.8 micrograms/dl vs. 7.2 micrograms/dl, p = .004), and for
      the 79 who had ever burned paint and metal and welded on outdoor structures
      compared to the 48 who had done none of these activities (8.6 micrograms/dl vs.
      6.8 micrograms/dl, p = .01). The 58 workers who had ever had workplace lead
      monitoring performed had higher lead levels (9.7 vs. 7.5 micrograms/dl, p =
      .003). Blood lead levels increased with age, and cigarette smoking. African
      Americans (N = 68) had higher lead levels (9.1 vs. 7.5 micrograms/dl, p = .01).
      There were only two women in the study, one with a lead level of 21 micrograms/dl
      and one, 7 micrograms/dl. Blood lead levels did not predict either systolic or
      diastolic blood pressure in this population. However, there was a significant
      interaction between race and lead as predictors of blood pressure, with blacks
      demonstrating a trend-significant correlation, and whites showing a
      nonsignificant but negative association. Demolition and hotwork on outdoor
      structures are known to cause acute episodes of lead poisoning. They also appear
      to cause slight but persistent increases in blood lead levels. Future workplace
      regulation should recognize and seek to maintain the low baseline now apparent
      even in urban, East Coast, construction workers.

PMID- 9028437
TI  - Stress among package truck drivers.
AB  - In 1992, a cross-sectional questionnaire study of package truck drivers in one
      company was conducted at four widely scattered sites throughout the US; 317
      drivers participated, representing 82% of those eligible. The package truck
      drivers scored significantly above the US working population comparison norm on
      all summary and individual scales derived from the SCL 90-R, indicating a
      substantial increase in psychologic distress for this group. The Global Severity
      Index, the best single summary measure of psychological distress in the SCL 90-R,
      revealed a mean T score for the drivers of 64.20, 91st percentile of the
      normative population. The group perceived significantly more daily stressful
      events than the average working adult, and their sensitivity to these events was
      also increased. Role overload, a component of the Occupational Stress Inventory,
      was the most consistent factor associated with symptoms of psychological distress
      on multiple regression analysis. This study suggests that job stress is a
      psychological health hazard for these drivers.

PMID- 9028438
TI  - An update of mortality from all causes among white uranium miners from the
      Colorado Plateau Study Group.
AB  - To place previously recognized mortality risks into the context of the total
      mortality from all causes, an updated retrospective cohort mortality study was
      conducted on 3,238 white males from the US Public Health Service cohort of
      Colorado Plateau uranium miners. Vital status was followed from 1960 through
      1990. Life-table analyses used combined New Mexico, Arizona, Utah, and Colorado
      mortality rates for external comparison and mortality risks within the lowest
      radon-exposure or duration-employed category for internal comparison.
      Significantly elevated SMRs were found for pneumoconioses (SMR = 24.1, 95% CI
      16.0-33.7), lung cancer (SMR = 5.8, 95% CI 5.2-6.4), tuberculosis (SMR = 3.7, 95%
      CI 1.9-6.2), chronic obstructive respiratory diseases (SMR = 2.8, 95% CI 2.2
      3.5), emphysema (SMR = 2.5, 95% CI 1.9-3.2), benign and unspecified tumors (SMR =
      2.4, 95% CI 1.0-4.6), and diseases of the blood and blood-forming organs (SMR =
      2.4, 95% CI 1.0-5.0). No significantly lowered SMRs were found for any disease.
      For lung cancer and pneumoconioses standardized rate ratios increased with
      increasing exposure to radon progeny or duration of employment. Most findings
      from this update are consistent with previous studies. Not observed were
      previously elevated SMRs for chronic nephritis and for acute alcoholism. New
      findings observed were elevated SMRs for benign and unspecified tumors and for
      diseases of the blood and blood-forming organs. The most important long-term
      mortality risks for the white uranium-miners continue to be lung cancer and
      pneumoconioses, for which SMRs remain significantly elevated after a mean period
      of 22.4 years since last uranium mining.

PMID- 9028439
TI  - Acute work injuries among electric utility linemen.
AB  - This analysis presents differences in acute work injury rates among electric
      utility linemen who perform different work tasks. Incidence-density rate ratios
      were the primary measure of association and are based on the work injury and
      person-time data for each job title. Logistic regression was used to model race,
      age, job experience, total inservice, prior injury, and time from prior injury.
      Transmission linemen had the lower acute injury rate with 18.9 per 100 person
      work-years (95% CI 16-20), distribution linemen had 27.8 per 100 person-work
      years (95% CI 27-28), and apprentice linemen had 43.3 per 100 person-work-years
      (95% CI 41-45). Injuries to the trunk and sprains and strains are the predominant
      injury categories. Having a prior lost time injury increases the risk for
      subsequent lost time injury for transmission linemen (OR = 1.6, 95% CI = 1.0-2.7)
      and for distribution linemen (OR = 1.5, 95% CI = 1.3-1.6).

PMID- 9028440
TI  - The Agricultural Health Study: factors affecting completion and return of self
      administered questionnaires in a large prospective cohort study of pesticide
      applicators.
AB  - Response rates were examined in a prospective epidemiologic study of individuals,
      mostly farmers, from Iowa and North Carolina seeking a pesticide applicator
      license during the period from 1994 through 1996. In the first year of enrollment
      16,535 farmers (representing 77% of eligible farmer applicators) enrolled in the
      study by completing a 17-page questionnaire administered at a pesticide training
      session; 47% of the enrolled farmers completed and returned a much longer take
      home questionnaire. The characteristics of farmers who completed only the
      enrollment questionnaire were quite similar to those of farmers who also
      completed and returned the take-home questionnaire. The most notable difference
      was the increased age of responders. Thus, the study population might have
      slightly higher cumulative farm exposures and slightly lower current farm
      exposures than the base population of all farmer applicators. The lack of
      evidence for substantial selection bias is reassuring for the Agricultural Health
      Study, and provides a measure of reassurance for other studies depending on the
      voluntary completion of self-administered questionnaires.

PMID- 9028441
TI  - Identifying comparison groups for evaluating occupational hearing loss: a
      statistical assessment of 22 industrial populations.
AB  - Finding appropriate comparison groups to study occupational hearing loss has been
      difficult. Recently, however, the National Institute for Occupational Safety and
      Health sponsored the complication of potentially useful data from 22 diverse
      industrial companies in the U.S.A. and Canada. We conducted a statistical
      evaluation to determine which of the 22 populations might be suited as comparison
      groups in future studies of workers exposed to hazardous noise. In a Cox
      Proportional Hazards model that included age and sex, the relative risk of
      developing hearing loss in each company was estimated at two, five, and ten years
      of follow-up. We ranked the companies based on their relative risks, and rated
      them on a five-point scale from "excellent" to "poor" to indicate their
      suitability as comparison groups. The risk profiles developed and other variables
      described in this study will assist researchers in selecting appropriate
      comparison groups for evaluating occupational hearing loss.

PMID- 9028442
TI  - Respiratory function in vineyard and orchard workers.
AB  - A group of 174 male vineyard and orchard workers was studied for the prevalence
      of acute and chronic respiratory symptoms and lung function changes. In addition,
      115 male control workers were studied for the prevalence of chronic respiratory
      symptoms. There was a significantly higher prevalence of dyspnea and chest
      tightness in exposed compared to control workers. In particular, exposed
      nonsmokers had significantly higher prevalences of dyspnea and chest tightness
      than controls this was found for exposed nonsmokers with both short (< or = 10
      years) and long (> 10 years) exposure. Smokers exposed for more than 10 years had
      significantly higher prevalences of chronic cough, chronic phlegm, chronic
      bronchitis, and chest tightness than smokers with shorter exposures (p < 0.01 or
      p < 0.05). Workers employed for more than 10 years had higher prevalences of most
      of the acute (shipt-related) symptoms than those workers with shorter employment;
      however, the differences were significant only for cough in smokers (p < 0.05).
      Significantly lower than predicted FVC values were measured in smokers and
      nonsmokers after both short and long duration of employment. Differences between
      measured and predicted FEV1, FEF50, and FEF25 were significant for workers
      employed for more than 10 years. A separate analysis of individual data as a
      percent of predicted values demonstrated that many workers had FVC (5.2%), FEV1
      (6.3%), FEF50 (27.6%), and FEF25 (40.2%) lower than 70% of predicted values.
      These data suggest that vineyard and orchard workers may develop acute and
      chronic respiratory symptoms and lung function changes which are, in part,
      related to environmental factors and to cigarette consumption.

PMID- 9028443
TI  - A follow-up study of job strain and heart disease among males in the NHANES1
      population.
AB  - Several studies have associated heart disease with job strain, defined as low job
      control and high job demands. We have studied incident heart disease (519 cases)
      and job strain among 3,575 males in NHANES1 survey who were currently employed at
      baseline in the early 1970s, and followed through 1987. Scores for job control
      and job demands were assigned to each subject based on current occupation at
      baseline. Controlling for conventional risk factors, we found no excess risk for
      those with the highest strain (lowest control and highest demands, rate ratio
      1.08). Those with highest job control did have significantly decreased risk (rate
      ratio 0.71, 95% CI 0.54-0.93). In blue-collar workers (58% of subjects) there was
      a significant inverse trend in risk with increasing job demands. Control for
      level of physical activity did not change this finding. A combination of high
      control and demand was protective among blue-collar workers (odds ratio 0.69,
      0.48-0.99). Our findings suggest that class-specific analyses are needed in
      studying job stress, and that "active" blue-collar workers with high control and
      high demand are protected against heart disease. The "job demand" variable may
      measure whether work is challenging rather than fast-paced. Our findings are
      limited by the use of assigned job scores based on job title.

PMID- 9028444
TI  - Marshall-Stickler phenotype associated with von Willebrand disease.
AB  - We report on 6 individuals from three different kindreds with Marshall-Stickler
      (MS) phenotype, with characteristic orofacial abnormalities, arthropathy,
      deafness, and eye findings, all of whom were discovered to have a mild bleeding
      diathesis and coagulation-study findings consistent with mild von Willebrand
      disease (vWD). MS syndrome has been linked in some cases to the type II
      procollagen gene (COL2A1) on chromosome 12q, and to the collagen XI gene
      (COL11A2) on chromosome 6. The von Willebrand factor (vWF) is encoded by a 180-Kb
      gene located on the short arm of chromosome 12. This is the first reported
      association of these two disorders.

PMID- 9028445
TI  - Autosomal dominant and sporadic radio-ulnar synostosis.
AB  - We report on seven cases of congenital radio-ulnar synostosis (RUS). Five were
      found in the same family and two were sporadic. In six the synostosis was
      bilateral and consistently involved the proximal end of the radius and ulna. In
      the familial cases the anomaly was inherited as an autosomal dominant trait and
      was associated with a Dubois sign and relative shortness of metacarpals number 4
      and 5 in two patients, and of number 2 in another patient, and of all phalanges
      of the 5th fingers. These observations suggest involvement of an ulnar
      developmental field. RUS does not seem to be rare in the Sicilian population.

PMID- 9028446
TI  - Developmental analysis of cardiovascular system of 45,X fetuses with cystic
      hygroma.
AB  - There have been few pathological investigations of 45,X embryos and fetuses from
      a developmental point of view. Since most 45,X embryos and fetuses are lost
      prenatally, it is important to investigate them morphologically in order to
      elucidate the pathogenesis of the abnormalities. In this study, 13 45,X fetuses
      with cervical cystic hygroma were examined between 12 and 23 weeks of pregnancy.
      Every case had a hypoplastic thymus. The aortic valve was bicuspid in 11 cases
      and unicuspid in 2 cases. The aortic arch showed tubular hypoplasia between the
      left carotid artery and the left subclavian artery in 12 cases and type B
      interruption in one case. Smooth muscle cells and elastic fibers were reduced in
      number in the hypoplastic aortic arch. These results suggest hypoplastic
      development of the fourth branchial arch. Combined abnormalities between the
      aortic arch and aortic valve are not infrequently observed in DiGeorge anomaly. A
      similar developmental mechanism apparently underlies the pathogenesis of 45,X
      embryos. Possible genes causing the abnormalities are discussed.

PMID- 9028447
TI  - Mental retardation, postaxial polydactyly, phalangeal hypoplasia, 2-3 toe
      syndactyly, unusual face, uncombable hair: new syndrome?
AB  - We report on a boy with unique somatic and skeletal manifestations. The syndrome
      consists of mental retardation, postaxial polydactyly, phalangeal hypoplasia, 2-3
      toe syndactyly, abnormal face and uncombable hair. A younger sib who died soon
      after the birth was probably also affected.

PMID- 9028448
TI  - Increased low-level chromosome 21 mosaicism in older individuals with Down
      syndrome.
AB  - During a study of the familial aggregation of Down syndrome (DS) and Alzheimer
      disease (AD), we observed an increase in mosaicism for disomy 21 in older
      individuals with DS. In a total of 213 DS subjects who were studied
      cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14
      of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report
      connotes "low-level" mosaicism, where all 15 individuals exhibited a modal
      chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of
      the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17,
      and X increased with age, and an inverse correlation between chromosome loss and
      size was also observed. Because older individuals had not been karyotyped at
      birth, it was not possible to determine whether our observations were due to
      either increased survival of mosaic individuals or accumulation of disomy 21
      cells via increased chromosome loss with aging of the trisomy 21 individual.
      Using a modeling approach involving life table methods, we obtained results that
      suggested acquired mosaicism as the predominant mechanism to explain our
      findings. These results support the hypothesis that as individuals with DS age,
      there is an increased loss of chromosome 21.

PMID- 9028449
TI  - Are there ethnic differences in deletions in the dystrophin gene?
AB  - We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of
      India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic
      deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of
      cases with deletion of single exons did not differ significantly from those with
      deletion of multiple exons. The distribution of deletions in studies from
      different countries was variable, but this was accounted for either by the small
      number of cases studied, or by fewer exons analyzed. It is concluded that there
      is likely to be no ethnic difference with respect to deletions in the DMD gene.

PMID- 9028450
TI  - Limb defects and congenital anomalies of the genitalia in an infant with
      homozygous alpha-thalassemia.
AB  - We describe an infant with homozygous alpha-thalassemia, genital abnormalities,
      and terminal transverse limb defects, whose limbs demonstrate evidence of loss of
      tissue and abnormal morphogenesis. We propose these defects were due to either
      severe fetal anemia or to vascular occlusion by abnormal erythrocytes, resulting
      in hypoxia of the developing distal limbs and genitalia.

PMID- 9028451
TI  - Limb defects in homozygous alpha-thalassemia: report of three cases.
AB  - Homozygosity for the South-Asian alpha-thalassemia (--SEA/) deletion is a serious
      hematological condition that results, in most cases, in intrauterine or postnatal
      death due to anemia and severe hypoxia of prenatal onset. A relationship between
      congenital abnormalities and intra-uterine hypoxia has been postulated. However,
      since homozygosity for the (--SEA/) deletion is most common in underdeveloped
      countries where detailed autopsies are lacking, the incidence of congenital
      abnormalities among these babies has not been well delineated. We report on three
      newborn infants, homozygous for the (--SEA/) deletion, who were born with limb
      defects. We postulate that this combination is the result of prenatal hypoxia
      which may affect other fetal body organs. This should be taken into consideration
      when prenatal treatment of affected fetuses, with intrauterine blood transfusion,
      is suggested.

PMID- 9028452
TI  - Ectrodactyly-ectodermal dysplasia-clefting syndrome and hypothalamo-pituitary
      insufficiency.
AB  - We report on 2 brothers with ectrodactyly-ectodermal dysplasia-clefting (EEC)
      syndrome and hypothalamo-pituitary insufficiency. Both had hypogonadotropic
      hypogonadism. One brother had partial TSH and prolactin deficiency, and the other
      had mild primary hypothyroidism, due most probably to irradiation therapy which
      he had undergone a few years earlier because of Hodgkin disease. The association
      of hypogonadotropic hypogonadism with EEC was reported once previously.
      Hypothalamopituitary dysfunction could be considered as yet another manifestation
      of EEC syndrome. This report reconfirms that EEC syndrome is a pleiotropic trait
      with reduced penetrance. Alternatively, we may be dealing with a (new) autosomal
      or X-linked recessive condition.

PMID- 9028453
TI  - Genetic defects at the UGT1 locus associated with Crigler-Najjar type I disease,
      including a prenatal diagnosis.
AB  - Characterization of the UGT1 gene complex locus encoding both multiple bilirubin
      and phenol UDP-glucuronosyltransferases (transferases) has been critical in
      identifying mutations in the bilirubin isoforms. This study utilizes this
      information to identify the bases of deficient bilirubin UDP
      glucuronosyltransferase activity encoded by the UGT1A gene for the major
      bilirubin isozyme, HUG-Br1, in 3 Crigler-Najjar type I individuals and the
      genotype of an at-risk unborn sibling of one patient. A homozygous and
      heterozygous two-base mutation (CCC to CGT) created the HUG-Br1P387R mutant of
      the major bilirubin transferase in 2 different Crigler-Najjar type I patients,
      B.G. and G.D., respectively. Both parents of B.G. and his unborn sibling, J.G.,
      were determined to be carriers of the P387R mutation. G.D. also contains the CAA
      to TAA nonsense mutation (G1n357st). Y.A. has a homozygous CT deletion in codons
      40/41. The HUG-Br1P387R mutant protein was totally inactive at the major pH
      optimum (6.4), but retained 26% normal activity at the minor pH optimum (7.6),
      which was 5.4% of the combined activities measured at the two pH values.

PMID- 9028454
TI  - Limb anomalies in DiGeorge and CHARGE syndromes.
AB  - Limb anomalies are not common in the DiGeorge or CHARGE syndromes. We describe
      limb anomalies in two children, one with DiGeorge and the other with CHARGE
      syndrome. Our first patient had a bifid left thumb, Tetralogy of Fallot, absent
      thymus, right facial palsy, and a reduced number of T-cells. A deletion of 22q11
      was detected by fluorescence in situ hybridization (FISH). The second patient,
      with CHARGE syndrome, had asymmetric findings that included right fifth finger
      clinodactyly, camptodactyly, tibial hemimelia and dimpling, and severe club-foot.
      The expanded spectrum of the DiGeorge and CHARGE syndromes includes limb
      anomalies.

PMID- 9028455
TI  - Microsatellite DNA markers detects 95% of chromosome 22q11 deletions.
AB  - Cono-truncal cardiac malformations account for some 50% of congenital heart
      defects in newborn infants. Recently, hemizygosity for chromosome 22q11.2 was
      reported in patients with the DiGeorge/Velo-cardio-facial syndromes (DGS/VCFS)
      and causally related disorders. We have explored the potential use of
      microsatellite DNA markers for rapid detection of 22q11 deletions in 19 newborn
      infants referred for cono-truncal heart malformations with associated DGS/VCFS
      anomalies. A failure of parental inheritance was documented in 84.2% of cases
      (16/19). PCR-based genotyping using microsatellite DNA markers located within the
      commonly deleted region allowed us either to confirm or reject a 22q11
      microdeletion in 94.3% of cases (18/19) within 24 hours. This test is now
      currently performed in the infants referred to us for a cono-truncal heart
      malformation as a first intention screening for 22q11 microdeletion.

PMID- 9028456
TI  - Tetra-amelia and splenogonadal fusion in Roberts syndrome.
AB  - Roberts-SC phocomelia syndrome comprises limb deficiencies of variable severity,
      facial clefts, and other anomalies. Tetra-amelia may also be associated with
      facial clefts and similar anomalies. We report on a female infant with severe
      tetra-amelia, micrognathia, cleft palate, splenogonadal fusion, and premature
      centromere separation. We propose that this represents the severe expression of
      the Roberts-SC phocomelia syndrome.

PMID- 9028457
TI  - Limb-pelvis hypoplasia/aplasia: a discrete entity in the fibuloulnar
      developmental field complex.
AB  - The limb-pelvis hypoplasia/aplasia (LPHA) syndrome is a rare condition of
      skeletal malformations affecting the ulnae, pelvic bones, fibulae and femora,
      sometimes associated with extraskeletal defects. Most reported patients are from
      the Middle East, and autosomal recessive inheritance was clearly demonstrated on
      the basis of multiple occurrences of affected sibs born to consanguineous
      matings. Here we report on a baby girl presenting with the phenotypic
      characteristics of LPHA. This is second observation of LPHA from Italy, and the
      fourth outside the Middle East. A paternal first cousin once removed had
      unilateral fibular hypoplasia and absence of the the 4th and 5th digital rays.
      The possible link between these cases is discussed in the light of the
      developmental field theory.

PMID- 9028458
TI  - Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome
      patients with an imprinting mutation.
AB  - Recent studies have identified a new class of Prader-Willi syndrome (PWS) and
      Angelman syndrome (AS) patients who have biparental inheritance, but neither the
      typical deletion nor uniparental disomy (UPD) or translocation. However, these
      patients have uniparental DNA methylation throughout 15q11-q13, and thus appear
      to have a mutation in the imprinting process for this region. Here we describe
      detailed clinical findings of five AS imprinting mutation patients (three
      families) and two PWS imprinting mutation patients (one new family). All these
      patients have essentially the classical clinical phenotype for the respective
      syndrome, except that the incidence of microcephaly is lower in imprinting
      mutation AS patients than in deletion AS patients. Furthermore, imprinting
      mutation AS and PWS patients do not typically have hypopigmentation, which is
      commonly found in patients with the usual large deletion. Molecular diagnosis of
      these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127,
      PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the
      simple molecular diagnostic analysis of PWS and AS patients with an imprinting
      mutation, as has been found for typical deletion or UPD PWS and AS cases. With
      the recent finding of inherited microdeletions in PWS and AS imprinting mutation
      families, our studies define a new class of these two syndromes. The clinical and
      molecular identification of these PWS and AS patients has important genetic
      counseling consequences.

PMID- 9028459
TI  - Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by
      fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A
      II, coagulation factor V, and antithrombin III.
AB  - We report on a 12-month-old Japanese boy with an interstitial deletion of the
      long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia,
      atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes
      equinovarus, low birth weight, growth/developmental retardation, and many minor
      anomalies. By conventional GTG-banding, his karyotype was first interpreted as
      46,XY,del(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by
      fluorescence in situ hybridization using 11 known cosmid clones as probes. His
      serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to
      1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum
      concentration and activity of antithrombin III (AT3, 1q23-q25.1) was low. The
      results indicated that localization of APOA2 and F5 are proximal to the deleted
      region and AT3 is located within the deletion extent in the patient.

PMID- 9028460
TI  - Novel insertion mutation in a non-Jewish Caucasian type 1 Gaucher disease
      patient.
AB  - Gaucher disease is the most prevalent lysosomal storage disorder. It is
      autosomalrecessive, resulting in lysosomal glucocerebrosidase deficiency. Three
      clinical forms of Gaucher disease have been described: type 1 (nonneuronopathic),
      type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). We performed
      PCR-thermal cycle sequence analysis of glucocerebrosidase genomic DNA and
      identified a novel mutation in a non-Jewish type 1 Gaucher disease patient. It is
      a C insertion in exon 3 at cDNA nucleotide position 122 and genomic nucleotide
      position 1626. This mutation causes a frameshift and, subsequently, four of the
      five codons immediately downstream of the insertion were changed while the sixth
      was converted to a stop codon, resulting in premature termination of protein
      translation. The 122CC insertion abolishes a Cac81 restriction endonuclease
      cleavage site, allowing a convenient and reliable method for detection using RFLP
      analysis of PCR-amplified glucocerebrosidase genomic DNA. The mutation in the
      other Gaucher allele was found to be an A-->G substitution at glucocerebrosidase
      cDNA nucleotide position 1226 that so far has only been reported among type 1
      Gaucher disease patients. Since mutation 122CC causes a frameshift and early
      termination of protein translation, it most likely results in a meaningless
      transcript and subsequently no residual glucocerebrosidase enzyme activity. We
      speculate that mutation 122CC may result in a worse prognosis than mutations
      associated with partial activity. When present in the homozygous form, it could
      be a lethal allele similar to what has been postulated for the other known
      insertion mutation, 84GG. Our patient, who is a compound heterozygote
      122CC/1226G, has moderately severe type 1 Gaucher disease. Her clinical response
      to Ceredase therapy that began 31 months ago has been favorable, though
      incomplete.

PMID- 9028461
TI  - Dubowitz syndrome in a boy without developmental delay: further evidence for
      phenotypic variability.
AB  - Dubowitz syndrome is an autosomal recessive condition characterized by pre- and
      postnatal growth retardation, eczema, telecanthus, epicanthal folds,
      blepharophimosis, ptosis, and broadening of the bridge and tip of the nose. The
      initial patients described had varying degrees of mental retardation and there is
      little information about long-term developmental outcome. We present a boy with
      Dubowitz syndrome who does not have developmental delays, providing additional
      evidence that the phenotype includes normal neurodevelopmental status.

PMID- 9028462
TI  - De novo trisomy 16p.
AB  - We report on a patient with psychomotor retardation and a pattern of
      malformations comprising single umbilical artery, craniofacial anomalies, severe
      truncal hypotonia, and lower-limb hyporreflexia. G-banding cytogenetics
      demonstrated a 16p+ chromosome. Parental chromosomes were normal. The use of
      fluorescent in situ hybridization (FISH) showed that this extra material derived
      from chromosome 16. High-resolution G-banding demonstrated a duplicated segment
      on the 16p arm, confirming our suspicion of a de novo tandem duplication; hence,
      the cytogenetic diagnosis was given as 46,XY,dir dup(16)(p11.2-->p12).

PMID- 9028463
TI  - Salivary gland disorders and heredity.
AB  - From personal observations, I review the genetic disorders of salivary gland
      development and function, including the lacrimo-auriculodentodigital (LADD)
      syndrome, autosomal dominant hypoplasia/agenesis of salivary and/or lacrimal
      glands, chronic recurrent sialadenitis, polycystic-dysgenetic disease of the
      parotids and salivary calculi.

PMID- 9028464
TI  - The Pointer syndrome: a new syndrome with skeletal abnormalities, camptodactyly,
      facial anomalies, and feeding difficulties.
AB  - We describe a brother and sister with a unique combination of skeletal findings
      including camptodactyly (phalangeal dislocations), facial anomalies, neonatal
      respiratory problems, and feeding problems due to poor suck. Metaphyseal
      splaying, osteopenia, endosteal bone apposition, campomelia, and multiple
      fractures characterize the other skeletal abnormalities. The parents are first
      cousins once removed and are unaffected. These cases appear to represent a
      previously undescribed autosomal recessive disorder.

PMID- 9028465
TI  - Hypertelorism and hypospadias associated with a de novo apparently balanced
      translocation between 8q22.3-23 and 20p13.
AB  - A de novo apparently balanced translocation involving chromosomes 8 and 20 was
      found in a 14-year-old boy with minor anomalies, mild skeletal abnormalities and
      ambiguous external genitalia including perineoscrotal hypospadias, rudimentary
      fused labioscrotal folds, bilateral cryptorchidism, and small penis. The
      karyotype was 46,XY, t(8;20)(q22.3-23;p13). No signs of other conditions known to
      be associated with structural anomalies of either chromosome 8 or 20 were present
      and incomplete masculinisation of the external genitalia appears to be the main
      component of the phenotype. Clinical and biological studies showed apparently
      normal testicular function in utero and after birth. Examinations excluded 5
      alpha-reductase deficiency or a block in any enzymatic steps of testosterone,
      glucocorticoid and mineralocorticoid biosynthesis. Coding sequences of the sex
      determining gene (SRY) and androgen receptor gene (AR) were found to be identical
      to those of a normal male excluding their role in the cause of the present
      condition. Since several other reports describe the association of hypospadias
      and hypertelorism with deletions or translocations involving 8q, we suggest that
      a locus necessary for male sex differentiation is located at distal 8q.

PMID- 9028466
TI  - Asymptomatic and late-onset ornithine transcarbamylase deficiency caused by a
      A208T mutation: clinical, biochemical and DNA analyses in a four-generation
      family.
AB  - We describe a 4-generation family in which a previously healthy 10-year-old boy
      died of late-onset ornithine transcarbamylase (OTC) deficiency. Pedigree analysis
      and allopurinol loading tests in female relatives were not informative. A
      missense mutation (A208T) in the OTC gene was detected in the deceased patient
      and in several clinically healthy male and female relatives, the oldest male
      being 97 years old. OTC deficiency was established in autopsy liver tissue of the
      propositus and liver biopsy samples of his sister, mother, and a maternal uncle.
      The males had 4% and 6% residual activity, respectively, the females 58% and 67%,
      respectively. The observed relation between the mutation and the decreased OTC
      activity in liver tissue of these subjects suggests that the mutation is a
      deleterious one. Late-onset, "mild" OTC deficiency can have a fatal or a
      favorable outcome. The disease can segregate undetected in families.

PMID- 9028467
TI  - Trisomy 18 mosaicism in a woman with normal intelligence, pigmentary dysplasia,
      and an 18 trisomic daughter.

PMID- 9028468
TI  - Malignant melanoma and Charcot-Marie-Tooth disease: a further case.

PMID- 9028469
TI  - Magnetic resonance imaging of the brain in Williams-Beuren syndrome.

PMID- 9028470
TI  - Linkage analysis in a family with the Opitz GBBB syndrome refines the location of
      the gene in Xp22 to a 4 cM region.
AB  - The Opitz GBBB syndrome (OS) is characterized in part by widely spaced inner
      ocular canthi and hypospadias. Recently, linkage analysis showed that the gene
      for the X-linked form to be located in an 18 cM region spanning Xp22. We have now
      conducted linkage analysis in a family previously published as having the BBB
      syndrome and found tight linkage to DXS7104 (Z = 3.3, theta = 0.0). Our data
      narrows the candidate region to 4 cM and should facilitate the identification and
      characterization of one of the genes involved in midline development.

PMID- 9028471
TI  - Effects of time and dilution on concentration of xanthine in frozen urine and
      plasma of dogs.
AB  - OBJECTIVE: To evaluate the effects of dilution on stability of xanthine in canine
      urine stored at -20 C, and to evaluate the effects of storage at -20 C on
      stability of xanthine in canine plasma. ANIMALS: 6 reproductively intact female
      Beagles, 3.9 to 4.2 years old and weighing 8.5 to 10.1 kg. PROCEDURE: Dogs were
      fed a 31.4% protein (dry weight), meat-based diet for 21 days, and administered
      allopurinol (15 mg/kg of body weight, q 12 h) during days 14 to 21; urine and
      plasma samples were obtained on day 22. Urine samples were preserved undiluted or
      diluted, and divided into 1-ml aliquots for storage at -20 C for 1 to 12 weeks.
      Plasma samples were divided into 1-ml aliquots for storage at -20 C for 1 to 12
      weeks. Urine and plasma xanthine concentrations were measured on day of
      collection (baseline) and after 1, 2, 4, 6, 9, and 12 weeks. RESULTS: Dilution of
      urine samples did not have a significant effect on consistency of xanthine
      concentration measured for up to 12 weeks of storage. Although xanthine
      concentration did not differ significantly between undiluted and diluted urine
      samples, average xanthine concentration measured in diluted samples was
      consistently higher, compared with that in undiluted samples. Compared with
      baseline values, plasma xanthine concentration was significantly lower at 6, 9,
      and 12 weeks of storage. CONCLUSIONS: Measurement of xanthine concentration is
      reproducible in undiluted or diluted urine samples for up to 12 weeks, although
      dilution may provide better results. Measurement of plasma xanthine concentration
      is reproducible in samples stored for up to 4 weeks. CLINICAL RELEVANCE: To
      ensure reproducibility of measurements of xanthine concentration in urine samples
      collected from dogs that are affected with urate uroliths and receiving
      allopurinol, urine should be diluted 1:20 with deionized water. These
      measurements may be useful for monitoring dogs that are receiving allopurinol for
      dissolution or prevention of urate uroliths.

PMID- 9028472
TI  - Decreased serum apolipoprotein B-100 and A-I concentrations in cows with ketosis
      and left displacement of the abomasum.
AB  - OBJECTIVE: To assess the relevance of hepatic lipidosis (fatty liver) in the
      development of ketosis and left displacement of the abomasum (LDA). SAMPLE
      POPULATION: Sera from 22 healthy cows in early lactation, 21 cows with ketosis,
      and 19 cows with LDA, and serum and liver specimens from 35 slaughtered cows with
      or without fatty liver, ketosis, and/or LDA. PROCEDURE: Apolipoprotein B-100 and
      A-I concentrations were measured in sera of healthy farm cows and of farm cows
      with ketosis and LDA. Serum apolipoprotein concentration, together with liver
      triglyceride content, also were surveyed in a subset of slaughtered cows.
      RESULTS: Compared with those in healthy cows or controls, apolipoprotein B-100
      and A-I concentrations were decreased in cows with ketosis and LDA. CONCLUSIONS:
      Decreases in apolipoprotein B-100 and A-I concentrations in cows with ketosis and
      LDA indicate that the 2 disorders may be intimately associated with fatty liver.
      CLINICAL RELEVANCE: Monitoring of the apolipoprotein B-100 and A-I concentrations
      during the stages of nonlactation and early lactation is helpful for detecting
      cows susceptible to ketosis and LDA.

PMID- 9028473
TI  - Effects of temperature on hematologic and serum biochemical profiles of hybrid
      striped bass (Morone chrysops x Morone saxatilis).
AB  - OBJECTIVE: To investigate the effect of water temperature on hematologic and
      biochemical analytes in hybrid striped bass. ANIMALS: Hybrid striped bass
      (reciprocal cross: female Morone chrysops x male M saxatilis) maintained in 2,000
      L tanks with undergravel filters. PROCEDURE: Fish were acclimated to 10, 18, 24,
      and 29 C water for 6 weeks prior to sample collection. Hematologic and serum
      biochemical profiles were then determined. Values were compared among the various
      temperatures, and with reference intervals previously determined. RESULTS: Most
      values were within or slightly outside the established reference intervals. The
      following analytes deviated notably from the reference interval: leukocyte,
      lymphocyte, and monocyte counts were lower than the reference intervals at 10 C;
      glucose values were lower at 10 and 18 C; calcium values were higher at 10 and 18
      C; and total protein, albumin, globulin, and chloride values were higher at 29 C.
      CONCLUSION: Separate reference intervals should be developed for analytes which,
      because of temperature, deviate notably from the reference interval.
      Modifications of the established reference intervals, by including fish from
      varied temperatures, should allow use of one reference interval for analytes,
      with only slight variation attributable to temperature. CLINICAL RELEVANCE:
      Determining the effects of temperature on the hematologic and biochemical values
      helps develop clinical pathology as a diagnostic tool in fish.

PMID- 9028474
TI  - Effects of ammonia and nitrate concentration on hematologic and serum biochemical
      profiles of hybrid striped bass (Morone chrysops x Morone saxatilis).
AB  - OBJECTIVE: To investigate the effects of poor water quality on hematologic and
      biochemical analytes in hybrid striped bass. ANIMALS: Hybrid striped bass
      (reciprocal cross: female Morone chrysops x male M saxatilis) maintained in 2,000
      L tanks with undergravel filters. PROCEDURE: Fish were acclimated to high ammonia
      (0.15 mg/L) and nitrate (200 mg/L) concentrations for 6 weeks prior to sample
      collection. Hematologic and biochemical profiles were determined for these fish
      and for fish kept under normal conditions (control). Comparisons were made among
      the 3 water qualities and with reference intervals determined previously.
      RESULTS: Significant differences in hematologic and biochemical analytes were
      observed between fish in the various groups; however, most of the values were
      within established reference intervals. All values from fish in the high ammonia
      concentration tank were either within the reference interval or not significantly
      different from control values. Fish from the high nitrate concentration tank had
      higher serum creatinine values and lower chloride values than did control fish,
      and both analytes were substantially outside the reference intervals. CONCLUSION:
      High ammonia concentration of 0.15 mg/L did not affect any of the blood analytes
      measured. The hypercreatininemia and hypochloremia observed in fish from the 200
      mg of nitrate/ml tank were considered to be pathologic changes associated with
      the high nitrate concentration. CLINICAL RELEVANCE: Determining the effects of
      water quality on hematologic and biochemical values helps to develop clinical
      pathology as a diagnostic tool in fish.

PMID- 9028475
TI  - Oral administration of tylosin phosphate for treatment and prevention of
      proliferative enteropathy in pigs.
AB  - OBJECTIVE: To evaluate the efficacy of orally administered tylosin phosphate for
      prevention and treatment proliferative enteropathy (PE) in pigs. ANIMALS:
      Crossbred pigs weaned at 24 days of age. PROCEDURE: Pigs were challenge exposed
      with an inoculum of Lawsonia intracellularis strain LR189/5/83. Seven control
      pigs received buffer solution. Of 33 challenge-exposed pigs, 8 were untreated.
      Two groups of challenge-exposed pigs were dosed orally with tylosin phosphate via
      a 2% stabilized premix, starting with 100 or 40 ppm 4 days before challenge
      exposure and continuing for 16 days, when the dose was reduced to 40 or 20 ppm,
      respectively, which was continued for 12 more days. Another group of challenge
      exposed pigs was dosed orally with 100 ppm of tylosin phosphate commencing 7 days
      after challenge exposure and continuing for 21 days. Pigs were euthanatized and
      necropsied 4 weeks after challenge exposure. RESULTS: The 8 untreated pigs had
      reduced weight gain, 3 of them had moderate diarrhea 3 weeks after challenge
      exposure. Five pigs had gross lesions of PE at necropsy. Seven pigs had
      histologic lesions of PE with numerous L intracellularis organisms. None of the
      pigs in the control, nonchallenge-exposed, or the 3 groups given tylosin
      phosphate before or after challenge exposure had clinical signs or lesions of PE.
      CONCLUSION AND CLINICAL IMPLICATIONS: Tylosin phosphate can be effective for
      prevention and for treatment of PE, using reported dosing schedules. We can
      experimentally induce PE, using the pure culture challenge-exposure model, for
      use in testing of treatments.

PMID- 9028476
TI  - Use of injectable lufenuron for treatment of infestations of Ctenocephalides
      felis in cats.
AB  - OBJECTIVE: To determine whether and for how long a single dose of a new
      injectable formulation of lufenuron would successfully control experimentally
      induced Ctenocephalides felis infestations in cats. ANIMALS: 15 cats (3 groups of
      5). PROCEDURE: Each group of cats was housed in a separate room. Each cat was
      infested with 150 fleas, and flea counts were checked weekly. Once flea
      populations had stabilized, cats were treated with lufenuron at a dosage of 5
      mg/kg of body weight, s.c. (group 1) or 10 mg/kg, s.c. (group 2). Group-3 cats
      were not treated. Flea counts were checked weekly for 18 weeks, and effectiveness
      was determined by comparing flea counts for treated cats with flea counts for
      control cats. Cats were reinfested with fleas during weeks 19, 26, 36, and 49,
      and flea counts were again determined weekly. RESULTS: Effectiveness for both
      dosages of lufenuron was > 90% by 5 weeks after treatment, > 95% by 9 weeks after
      treatment, and > 98% by 13 weeks after treatment. Reinfestations performed during
      weeks 19 and 26 were well controlled (ie, > 90% reduction in flea counts,
      compared with control group) in both groups of cats treated with lufenuron.
      Reinfestations performed during week 36 were well controlled only in cats treated
      with lufenuron at the higher dosage. Reinfestations performed during week 49 were
      not controlled in either group of treated cats. CONCLUSIONS: A single dose of the
      new injectable formulation of lufenuron should control flea populations in cats
      for up to 26 weeks, even among cats that are periodically reinfested with fleas.

PMID- 9028477
TI  - Alterations in specific activity of glucose-6-phosphatase in laboratory rats
      after leptospiral exposure followed by triiodothyronine administration.
AB  - OBJECTIVE: To determine the effect of leptospirosis on thyroid hormone induction
      of the specific activity of hepatic microsomal glucose-6-phosphatase in
      laboratory rats. ANIMALS: Male Fisher 344 rats, 6 and 24 months old, healthy and
      infected with leptospirosis. PROCEDURE: The maximal velocity of glucose-6
      phosphatase in intact and detergent-disrupted hepatic microsomes was assayed in
      duplicate or triplicate at 5 substrate concentrations, by monitoring the release
      of inorganic phosphate at 0-, 5-, and 10-minute intervals. The method of least
      squares was used to determine the velocity of the reactions. The level of
      statistical significance was determined, using the Student's t-test for unpaired
      data. Thyroid hormone (40 micrograms of T3/ 100 g of body weight) was
      administered for 5 consecutive days prior to sacrifice. RESULTS: Leptospirosis
      significantly increased the specific activity of the translocase component of
      glucose-6-phosphatase in old, but not young, rats. The activity of the
      translocase increased more than three-fold in untreated, infected old animals,
      compared with untreated, healthy old animals. Thyroid hormone induced a two- and
      threefold increase in the specific activities of the translocase in young and old
      healthy animals, respectively. Thyroid hormone did not increase the activity of
      the translocase in old animals infected with leptospirosis. CONCLUSIONS AND
      CLINICAL RELEVANCE: Leptospirosis alters the specific activity and induction by
      thyroid hormone of the translocase component of hepatic microsomal glucose-6
      phosphatase in old male Fisher 344 rats. It is necessary to be aware of possible
      alterations in hepatic membrane-bound enzymes after leptospiral infection of
      older laboratory animals.

PMID- 9028478
TI  - Effects of choreito consumption on urine variables of healthy cats fed a
      magnesium-supplemented commercial diet.
AB  - OBJECTIVE: To investigate the effect of choreito consumption (500 mg/kg of body
      weight/d) on struvite crystal formation and signs of lower urinary tract disease
      (LUTD) in cats consuming a commercial canned diet with 0.5% added inorganic
      magnesium. SAMPLE POPULATION: 6 male and 6 female adult cats, all considered to
      be clinically normal on the basis of physical examination findings; results of
      CBC, serum biochemical analyses, urinalyses, and urine cultures; and freedom from
      urolithiasis on the basis of urethrocystoscopic (females) or urethrocystographic
      (males) findings. PROCEDURE: Diets were fed for 12 weeks, or until appearance of
      signs of LUTD, including dysuria, hematuria, urine pH > 7.0, and severe struvite
      crystalluria. Presence of at least 2 of these signs was required for removal from
      study. Urine specimens were examined for electrolytes, struvite crystal content,
      and hematuria. RESULTS: Results for urine variables were compared between groups
      at 4 weeks, because of reduction in cat numbers attributable to removal from
      study. Struvite crystal content of 24-hour urine specimens was significantly
      lower for cats fed the choreito-containing diet. Moreover, frequency and severity
      of hematuria were significantly decreased in cats fed the choreito-containing
      diet. Correlation between hematuria and struvite crystal content was not observed
      in either group. Additionally, all 6 cats fed the diet without choreito had been
      removed from study by day 58 because of signs of LUTD. Of the 6 cats fed the
      choreito-containing diet, 2 completed the 12-week study. CLINICAL RELEVANCE:
      Choreito may be beneficial for relief of some signs of struvite-associated LUTD
      disease in cats.

PMID- 9028479
TI  - Effects of choreito and takushya consumption on in vitro and in vivo struvite
      solubility in cat urine.
AB  - OBJECTIVE: To determine the effects of the takushya portion of choreito, a
      traditional Chinese treatment for urolithiasis, on urine and struvite crystal
      variables in cats fed diets containing takushya. SAMPLE POPULATION: 6 male and 6
      female adult cats, all considered to be clinically normal on the basis of
      physical examination findings, results of CBC, serum biochemical analyses,
      urinalyses, and urine cultures; and freedom from urolithiasis on the basis of
      urethrocystoscopic (females) or urethrocystographic (males) findings. PROCEDURE:
      Cats were fed a commercial canned diet supplemented with 0.1-mg of takushya/kg of
      body weight, or with 0.5 mg of choreito/kg. Diets were fed, using a Latin-square
      design, to 3 groups of 4 cats (2 male, 2 female) each for 2 weeks, followed by
      blood and 24-hour urine sample collections. RESULTS: Consumption of takushya,
      which comprises 20% by weight of choreito, was not associated with adverse
      effects in cats at the amounts provided during the period of study. Moreover,
      takushya was responsible for most of the effect of choreito consumption on
      reduction of urine pH, and approximately half its ability to reduce struvite
      crystal formation in cat urine. CLINICAL RELEVANCE: Alternative treatments for
      struvite urolithiasis in cats may be feasible.

PMID- 9028480
TI  - Cardiopulmonary effects of propofol infusion in llamas.
AB  - OBJECTIVE: To evaluate selected cardiopulmonary responses to propofol 2 infusion
      rates in nonpretreated llamas breathing room air. ANIMALS: 5 adult llamas (3
      males, 2 females) with mean +/- SD body weight of 135 +/- 17.7 kg. PROCEDURE:
      After anesthesia induction with propofol (2 mg/kg of body weight, IV), llamas
      received either propofol infusion 0.2 mg/kg/min (group 1) or 0.4 mg/kg/min (group
      2) for 60 minutes. Measurements, taken before anesthesia induction and at regular
      intervals during infusion were: direct blood pressures, heart and respiratory
      rates, cardiac output, and arterial blood gas tensions. Systemic and pulmonary
      vascular resistance, cardiac and stroke indices, and plasma bicarbonate and base
      excess concentrations were calculated. RESULTS: At 3 to 60 minutes after either
      dosage of propofol, PaCO2 and heart rate increased in all llamas; at the same
      time, PaO2 and arterial pH decreased. Mean pulmonary artery and central venous
      pressures, and stroke index decreased at 3 to 60 minutes after either dosage of
      propofol. Mean arterial pressure decreased at 30 to 60 minutes after infusion of
      0.4 mg of propofol/kg/min; pulmonary arterial wedge pressure decreased at 20 to
      40 minutes and 3 to 60 minutes after infusion of 0.2 and 0.4 mg of
      propofol/kg/min, respectively. Mean time from termination of infusion to sternal
      recumbency was 7 (group 1) and 13 (group 2) minutes. Standing was achieved in a
      mean 11 (group 1) and 22 (group 2) minutes. CONCLUSION: Propofol infusion rate of
      0.2 mg/kg/min was considered too low to maintain a suitable depth of anesthesia,
      but 0.4 mg/kg/min was considered sufficient for noninvasive procedures with
      minimal cardiopulmonary depression.

PMID- 9028482
TI  - Resynthesis of glycogen in skeletal muscle from standardbred trotters after
      repeated bouts of exercise.
AB  - OBJECTIVE: To determine glycogen resynthesis rate and changes in plasma
      metabolite concentrations in horses before and after repeated exercise. ANIMALS:
      6 clinically normal Standardbred trotters. PROCEDURE: Horses trotted distances of
      3,000, 3,000, and 2,000 m (trial A) and 3 days later, trotted 2,100, 2,100, and
      1,600 m (trial B). Horses had 1 hour rest periods between bouts of exercise.
      Trotting speed was increased with each exercise bout, up to a near maximal.
      Muscle biopsy specimens and venous blood samples were obtained before each trial
      and 0, 4, 24, 48, and 72 hours after the third bout. Blood samples were also
      taken between exercise bouts. Muscle glycogen content and plasma glucose,
      glycerol, nonesterified fatty acid, and triglyceride concentrations were
      determined. RESULTS: Muscle glycogen content was significantly decreased
      immediately after exercise from 473 +/- 45 to 329 +/- 79 mmol/kg of dry weight in
      trial A, and from 472 +/- 128 to 347 +/- 59 mmol/kg in trial B. Further decreases
      were measured 4 hours after exercise. Glycogen resynthesis was negligible 24
      hours after exercise. Basal muscle concentrations of glycogen were obtained 72
      hours after exercise in trial A (472 +/- 128 mmol/kg), but not in trial B (279 +/
      52 mmol/kg). Plasma concentrations of glucose were greater than or equal to
      before-exercise values. Plasma concentrations of lipid metabolites, glycerol,
      triglycerides, and nonesterified fatty acids, were less than before-exercise
      values 2 to 72 hours after exercising. CONCLUSIONS: Repeated bouts of exercise
      decrease glycogen repletion rate, which is not attributable to hypoglycemia, but
      may be influenced by limited availability of lipids for energy production.

PMID- 9028481
TI  - Effects of a carfentanil-xylazine combination on cardiopulmonary function and
      plasma catecholamine concentrations in female bongo antelopes.
AB  - OBJECTIVE: To determine the effects of an i.m. administered carfentanil-xylazine
      combination on cardiopulmonary variables and plasma catecholamine concentrations
      and to validate use of pulse oximetry in bongo antelopes. ANIMALS: 8 healthy
      adult females. PROCEDURE: Antelopes were immobilized with carfentanil citrate
      (8.3 micrograms/kg of body weight, i.m.) and xylazine hydrochloride (0.79 mg/kg,
      i.m.). Hematologic values and plasma biochemical and catecholamine concentrations
      were determined at the beginning and end of immobilization. Immediately after
      induction of immobilization and every 15 minutes thereafter, cardiopulmonary
      variables were determined. RESULTS: Induction time after carfentanil-xylazine
      administration was 6 +/- 2 minutes. At 15 and 45 minutes after immobilization and
      thereafter, significant decrease in heart and respiratory rates, respectively,
      were observed. After 15 minutes of immobilization, all antelopes had developed
      mild hypoxemia, which resolved after nasal insufflation with 100% oxygen. Pulse
      oximetry readings underestimated arterial blood gas values, but reliably
      indicated trends in arterial oxygen desaturation. Antelopes developed hypoxemia
      after oxygen administration was terminated at the end of the procedure, prior to
      reversal of immobilization. Norepinephrine concentrations increased significantly
      (P < 0.05), and 3,4-dihydroxyphenylacetic acid concentrations decreased
      significantly at the end of the anesthetic event. Immobilization of all antelopes
      was reversed, using antagonists naltrexone and yohimbine hydrochloride. Time to
      standing was 3 +/- 1 minutes, and renarcotization was not observed. CONCLUSIONS
      AND CLINICAL RELEVANCE: The carfentamil-xylazine combination at the dosage used
      induced hypoxemia, pronounced arterial hypertension, and significant increase in
      plasma norepinephrine and decrease in plasma 3,4-dihydroxyphenylacetic acid
      concentrations in bongo antelopes. Supplemental administration of oxygen is
      recommended. Pulse oximetry is a useful tool to monitor trends in arterial oxygen
      desaturation, but does not substitute for arterial blood gas analysis.

PMID- 9028483
TI  - Skeletal muscle characteristics and metabolic response to exercise in young
      standardbreds.
AB  - OBJECTIVE: To determine whether performance capacity in a group of young trained
      Standardbreds is related to skeletal muscle characteristics and metabolic
      response to exercise. ANIMALS: 13 clinically normal 2-year-old Standardbreds.
      PROCEDURE: Venous blood and middle gluteal muscle biopsy samples were obtained
      from each horse within 1 to 2 minutes after trotting at high speed for 1,600 m.
      RESULTS: There was a positive correlation between plasma lactate and muscle
      glucose-6-phosphate (G-6-P) concentrations and trotting speed. There was a
      negative correlation between muscle adenosine triphosphate concentration and
      trotting speed, plasma lactate concentration, and muscle lactate and G-6-P
      concentrations. Muscle concentration of G-6-P was positively correlated with
      muscle lactate and plasma lactate concentrations. Percentage of type-1, -2A, and 
      2B fibers in skeletal muscle and muscle enzyme activities of hexokinase, 3-OH
      acyl-CoA dehydrogenase, lactate dehydrogenase, and citrate synthase were not
      correlated with trotting speed. CONCLUSION: Speed of trotting at a distance of
      1,600 m in young trained Standardbreds is related to the ability of muscle to
      produce energy by use of anaerobic glycolysis.

PMID- 9028485
TI  - Use of dew-point hygrometry, direct sweat collection, and measurement of body
      water losses to determine sweating rates in exercising horses.
AB  - OBJECTIVE: To compare dew-point hygrometry, direct sweat collection, and
      measurement of body water loss as methods for determination of sweating rate (SR)
      in exercising horses. ANIMALS: 6 exercise-trained Thoroughbreds. PROCEDURE: SR
      was measured in 6 horses exercising at 40% of the speed that elicited maximum
      oxygen consumption for 45 km, with a 15-minute rest at the end of each 15-km
      phase. Each horse completed 2 exercise trials. Dew-point hygrometry, as a method
      of local SR determination, was validated in vitro by measurement of rate of
      evaporative water loss. During exercise, local SR was determined every 10 minutes
      by the following 2 methods: (1) dew-point hygrometry on the neck and lateral area
      of the thorax, and (2) on the basis of the volume of sweat collected from a
      sealed plastic pouch attached to the lateral area of the thorax. Mean whole body
      SR was calculated from total body water loss incurred during exercise. RESULTS:
      Evaporation rate measured by use of dew-point hygrometry was significantly
      correlated (r2 = 0.92) with the actual rate of evaporative water loss. There was
      a similar pattern of change in SR measured by dew-point hygrometry on the neck
      and lateral area of the thorax during exercise, with a significantly higher SR on
      the neck. The SR measured on the thorax by direct sweat collection and by dew
      point hygrometry were of similar magnitude. Mean whole body SR calculated from
      total body water loss was not significantly different from mean whole body SR
      estimated from direct sweat collection or dew-point hygrometry measurements on
      the thorax. CONCLUSIONS: Dew-point hygrometry and direct sweat collection are
      useful methods for determination of local SR in horses during prolonged, steady
      state exercise in moderate ambient conditions. Both methods of local SR
      determination provide an accurate estimated of whole body SR.

PMID- 9028484
TI  - Decreased pulmonary arterial endothelium-dependent relaxation in heartworm
      infected dogs with pulmonary hypertension.
AB  - OBJECTIVE: To investigate the contractility of pulmonary arterial smooth muscle
      and the relation between pulmonary hypertension and endothelium-derived relaxing
      factor in canine heartworm disease. ANIMALS: 18 noninfected control and 9
      heartworm-infected dogs. PROCEDURE: Mean pulmonary arterial blood pressure was
      measured in vivo, and tension of pulmonary arterial strips was measured by use of
      the isometric tension method. RESULTS: After phenylephrine (10(-5)M)-induced
      contraction of the pulmonary vascular smooth muscle, carbamylcholine chloride
      (CCh, 10(-6)M) caused more relaxation of the vascular smooth muscle of
      noninfected, dogs than that of heartworm-infected dogs. Furthermore, the degree
      of CCh-induced relaxation was inversely correlated with mean pulmonary arterial
      blood pressure in the noninfected and the heartworm-infected dogs. The CCh
      induced relaxation was inhibited by pretreatment with NG-nitro-L-arginine methyl
      ester hydrochloride (10(-5)M), and in reversed dose-dependent manner by L
      arginine (10(-4) to 3 x 10(-2)M). Sodium nitroprusside (10(-8) to 10(-5)M) caused
      a dose-dependent relaxation in all vessels, and there was no significant
      difference in the relaxation responses in both groups except at 10(-7)M for
      vessels with intact endothelium from noninfected dogs. CONCLUSION: The depression
      of endothelium-dependent relaxation is correlated with the pulmonary arterial
      blood pressure in heartworm-infected dogs, suggesting that the decrease is one of
      the essential factors for the genesis of pulmonary hypertension in canine
      filariasis.

PMID- 9028486
TI  - Pregnancy-associated changes in material properties of the third metacarpal
      cortical bone in mares.
AB  - OBJECTIVE: To investigate the effect of late gestation, age, and parity on
      material properties of third metacarpal (MCIII) cortical bone in mares. ANIMALS:
      8 healthy mares (treatment group) that died or were euthanatized within 24 hours
      after parturition because of foaling complications and 6 age-matched, healthy,
      nonpregnant mares (control group). PROCEDURES: After random assignment for
      mechanical testing and microradiography, the dorsal half of transverse mid
      diaphyseal sections of each MCIII bone was divided into lateral, dorsal, and
      medial regions. Cylinders of bone from each of the 3 regions were tested in
      compression in a single cycle to failure. Contact microradiographic views were
      taken of 100-microns-thick sections prepared from methylmethacrylate-embedded
      transverse dorsal region specimens, which were further divided into periosteal,
      intracortical, and endosteal regions for assessment of bone mineral density and
      porosity. RESULTS: Postpartum mares had lower yield strain in the dorsal and
      medial regions and failure strain in the medial region. Increasing parity was
      associated with decreasing elastic modulus in the dorsal region and yield stress
      and failure stress in the lateral region. Age and parity were positively
      correlated (r = 0.865; P = 0.0001), but significant correlations were not found
      between treatment group and age or between treatment group and parity. Increasing
      age and parity were associated with increasing porosity in the periosteal region.
      CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the material properties
      evaluated for MCIII cortical bone in late pregnancy, any increased risk for
      fractures in mares in late gestation may be related to parity or age or both, and
      less likely to pregnancy pese.

PMID- 9028487
TI  - Effects of parathyroidectomy on induced renal failure in dogs.
AB  - OBJECTIVE: To determine the effects of parathyroid hormone (PTH) depletion on
      dogs with induced chronic renal failure. ANIMALS: 2 groups of 26 mixed-breed dogs
      of both sexes (13 were parathyroidectomized [PTX] and 13 had sham surgery).
      PROCEDURE: After surgical reduction of renal mass and PTX, dogs were selected for
      a 24-month period of study and monitored for clinical, hematologic, blood
      biochemical, and organ function status. On development of uremia or after 24
      months, dogs were euthanatized, and tissues were examined. RESULTS: Higher
      survival rate and smaller decrement in renal function (glomerular filtration
      rate) were observed in PTX dogs, compared with those that had sham surgery, but
      values did not reach statistical significance. The PTX dogs remained hypocalcemic
      during the study and had lower serum Ca2+ X P product values. Regardless of
      parathyroid state, survivors and fatalities could be separated on the basis of
      serum Ca2+ X P product values. Parathyroidectomy did not prevent renal deposition
      of calcium, and renal lesions were poorly correlated with renal cortical calcium
      concentration. Abnormalities reported in dogs with renal failure, which were
      attributed to PTH (glucose intolerance, pulmonary hypertension), were not
      observed in PTX dogs or those that had sham surgery. CONCLUSIONS AND CLINICAL
      RELEVANCE: PTX had beneficial effects, but these were mediated via changes in
      mineral homeostasis rather than via direct effects of PTH. Results attributable
      to PTX were similar to those previously obtained by dietary restriction of
      phosphate intake.

PMID- 9028488
TI  - Final stretch for the totally implantable TAH.

PMID- 9028490
TI  - Double filtration plasmapheresis for the treatment of rheumatoid arthritis: a
      study of 21 cases.
AB  - The treatment of rheumatoid arthritis remains difficult and often controversial.
      Plasma exchange has been advocated in some cases. In the present study 71
      sessions of double filtration plasmapheresis (DFPP) were performed in 21 patients
      with rheumatoid arthritis in an average of 3.7 +/- 1.1 sessions per patient
      within 1-2 weeks. Seven patients had received prednisone, and all the patients
      had received nonsteroid anti-inflammatory drugs with poor results. Although after
      the DFPP therapy, only 2 patients were still receiving nonsteroid anti
      inflammatory drugs, the function capacities improved in all patients. Five out of
      8 positive rheumatoid factors became negative for the group. These results
      suggest that DFPP could be a regular therapy for rheumatoid arthritis.

PMID- 9028489
TI  - Hemodialysis urea rebound and membrane biocompatibility: accuracy of Kt/V
      estimations.
AB  - To date, the magnitude, causes, and factors that govern urea rebound are not
      clearly defined. This study was undertaken to determine the possible influence of
      the biocompatibility of dialyzer membrane on urea rebound and to assess the
      participation of rebound in the calculation of Kt/V-urea by different methods.
      Blood urea samples were obtained before, and at 2, 30, and 60 min
      posthemodialysis in 8 patients undergoing dialysis with 2 different membranes,
      Cuprophan and polyacrylonitrile (24 sessions with each membrane). Urea rebound
      was documented in all patients. The degree of rebound was large, 20%, and it was
      achieved within 30 min after the end of dialysis. Urea rebound was observed with
      both Cuprophan and polyacrylonitrile membranes, without significant differences.
      Kt/V-urea significantly decreased (p < 0.001) by all methods when urea rebound
      was incorporated. We conclude that urea rebound is clinically very important and
      is not influenced by the biocompatibility of the dialyzer membrane. This
      phenomenon must be taken into account in the calculation of Kt/V; otherwise, it
      might be overestimated.

PMID- 9028491
TI  - Hepatocytes entrapped in collagen gel following 14 days of storage at 4 degrees
      C: preservation of hybrid artificial liver.
AB  - Preservation of hepatocytes is a key technical factor toward the successful
      clinical application of hybrid artificial livers. It was possible to culture
      hepatocytes that had been preserved with collagen gel for 8 and 14 days in 4
      degrees C University of Wisconsin solution. Phase-difference and scanning
      electron microscopy showed that most of the stored hepatocytes maintained a round
      shaped morphology. In the 14 day preservation group, on Days 2 and 8,
      respectively, ureogenesis was 98.3% and 69.6%, gluconeogenesis was 65.2% and
      80.7%, lidocaine clearance was 81.7% and 72.5%, urea synthesis after ammonia load
      was 47.6% and 57.5% of those in the comparable control group. This implies that
      preserved hepatocytes maintained adequate functional capability even after 14
      days of preservation. We suggest that our preservation method will be valuable
      for the future application and development of a practical hybrid artificial
      liver.

PMID- 9028492
TI  - Design of hollow fiber modules for uniform shear elution affinity cell
      separation.
AB  - Large-scale monoclonal antibody based systems for the selection of cell subsets
      will play a prominent role in the development of hematotherapy and graft
      engineering. Hollow fiber systems for affinity cell separation rely on the
      generation of uniform fluid shear stress at the lumenal attachment interface.
      Potential mechanisms for nonuniformity of lumenal wall shear stress are fiber
      wall permeation fluxes driven by the pressure gradient along individual fibers
      and the influence of inlet header dynamic pressure on the radial distribution of
      axial flow within the fiber module. Dimensional analysis and numerical solution
      of the flow field within the lumen of a hollow fiber module illustrate the main
      physical criteria for design of hollow fiber modules. There will be a nearly
      uniform distribution of flow within the fiber bundle provided that the dynamic
      inlet pressure is small in comparison with the pressure drop along fibers. Fiber
      wall permeation fluxes will have a negligible effect on axial flow rate for
      nonporous membranes such as Cuprophan.

PMID- 9028493
TI  - Stent fracture in Wessex porcine heart valve bioprostheses.
AB  - By January 1994, a total of 40 Wessex porcine bioprostheses (21 mitral, 18
      aortic, and 1 tricuspid) were explanted from 31 subjects. They belonged to a
      series of 150 patients who received 184 of such prostheses in our unit. Seventeen
      of these explanted prostheses were available for study, and 11 of them presented
      some sort of stent fracture or fissuring (mean of 3.6 +/- 1.6 fractures per
      prosthesis). The disruption occurred in all cases at the base of the commissural
      arch or at the commissural bar of the stent. The fractures were not detected
      clinically nor echo-cardiographically before reoperation, and most valves were
      explanted for reasons other than the stent rupture itself. The actuarial
      probability of freedom from stent fracture in our series is 66 +/- 12% at 9 years
      of follow-up. In our experience, fracture of the stent is an important mode of
      structural dysfunction of the Wessex porcine bioprostheses.

PMID- 9028494
TI  - Are intraaortic balloons suitable for reuse? A survey study of 112 used
      intraaortic balloons.
AB  - To assess the safety of reusing single-use intraaortic balloon devices (IABs),
      112 used devices were investigated in terms of physical integrity, gas leakage
      inspection, mechanical performance, surface chemistry and morphology, and
      physical stability. These IABs were all used clinically only once, and the
      duration of the IABs in vivo ranged from 6 to 312 h. Macroscopic examination of
      the balloons and the outer catheters revealed no obvious change in either shape
      or color. No discernible abrasions or cracks were observed on the balloons.
      However, 61% of the balloons were creased, and 40% of the central lumens and 21%
      of the sheaths showed visible bending flaws. Moreover, 65% of the balloons and
      38% of the central lumens were contaminated by visible residual organic debris.
      The physical integrity of each device was verified in a specially designed
      leakage-fatigue tester for 72 h. Ninety-seven percent of the devices passed the
      leakage inspection. Stress-strain testing, differential scanning calorimetry,
      attenuated total reflection-Fourier transform infrared, and scanning electron
      microscopy analyses clearly indicated that there were no significant differences
      in the mechanical properties, bulk material morphology, surface chemistry, and
      external surface morphology between the used balloons and virgin controls.
      Although some surface modifications occurred on the internal side of the
      balloons, the external surfaces of most balloons suffered no trauma. Most of the
      used IABs examined in this study maintained physical and mechanical properties
      similar to those of the virgin devices. The chemistry of the balloon material was
      stable after short-term in vivo use. However, it does not seem possible to
      establish a rigorous protocol of cleaning, sterilization, and inspection to
      guarantee a safer reuse of these devices. The presence of residual organic debris
      that cannot be eliminated results in an imperative preclusion not to reuse the
      IABs.

PMID- 9028495
TI  - The implantable fuzzy controlled Helmholtz-left ventricular assist device: first
      in vitro testing.
AB  - To perform first experimental tests for validation of a new left ventricular
      assist device (LVAD) with a high efficiency energy converter, a new pump design
      and a novel type of perfusion control, a functional labtype, were manufactured.
      With a stroke volume of 65 ml, a total pump housing volume of 450 ml (including
      valves and connectors), and a weight of 430 g, it is one of the smallest and
      lightest implantable pulsatile electromechanical LVADs. Pulsatile operation is
      generated by a special reduction and displacement gear which transforms a uniform
      rotational movement of a sensorless, electronically commutated DC motor into a
      translatory pusher plate movement. A prolonged duration for filling (60% of the
      cycle time) supports full-empty pumping and consequently a high overall pump
      efficiency. Active adaptation of output flow to organ perfusion demand is
      achieved by changing the rotational speed of the motor by means of a sensorless
      fuzzy controller, which detects preload and afterload induced effects at the
      motor current input. First in vitro test results obtained within a circulatory
      mock loop that simulates physiological preloads and afterloads are presented.
      They comprise preload sensitivity and the function of the novel perfusion
      controller as well as preload and afterload related flow data. The results prove
      the feasability of the energy conversion with the novel gear and control concept
      for an implantable electromechanical pulsatile LVAD.

PMID- 9028496
TI  - Mechanical white blood cell damage in rotary blood pumps.
AB  - Mechanical trauma of white blood cells (WBC) due to the operation of a rotary
      blood pump was examined, using a simple method of trypan blue dye exclusion test
      for a cell viability measurement. The degree of WBC trauma was investigated using
      a roller pump (RP) and 3 commercially available centrifugal pumps (Bio-Medicus
      [BP], Capiox [CP], Nikkiso [NK]), and compared with the red blood cell (RBC)
      trauma. Each pump was operated 3 times at a flow rate of 5 L/min against the
      total pressure head of 350 mm Hg for 6 h in a mock circuit with 400 ml of fresh
      bovine blood. Blood was sampled at 2 h intervals measuring plasma free hemoglobin
      concentration and the percentage of damaged WBC in the trypan blue dye exclusion
      test. Each pump demonstrated a linear increase in the degree of WBC trauma, and
      there were differences among the tested pumps (RP > BP > CP > NK). These findings
      were similar to those of the free hemoglobin measurements. To compare the degree
      of RBC and WBC trauma, the probability (gamma, omega) of RBC and WBC to be
      damaged was calculated, respectively. gamma = delta DRBC/delta N, omega = delta
      DWBC/delta N where DRBC and DWBC are the ratios of the damaged RBC and WBC,
      respectively, and N is the passing number defined as Qt/V (Q, flow rate; t, time;
      V, circulating volume). The data of this study demonstrated that the omega value
      was approximately 20 times or more greater than the gamma equally in all the
      tested pumps. This suggests that a WBC is more vulnerable to mechanical damage by
      a rotary blood pump than a RBC.

PMID- 9028497
TI  - Material of the double pivot bearing system in the Gyro C1E3 centrifugal pump.
AB  - A double pivot bearing system is adopted for the Gyro C1E3 centrifugal blood pump
      to achieve a completely sealless structure that prevents blood leakage and
      thrombus formation around the shaft. The double pivot bearing system is also a
      critical factor for blood trauma and durability of the C1E3 pump. This study
      focuses on the double pivot bearing material. The pump with the male ceramic and
      female polyethylene pivots (PE) was compared with the pump with the male ceramic
      and female ceramic pivots (CRM), pertaining to stability of the impeller spinning
      motion, hemolysis, and durability. At first, the wear rate of the pivots was
      recorded after operating the pumps in various rotational speeds. As for
      hemolysis, in vitro tests were carried out using fresh bovine blood in 2
      conditions (5 L/min, 350 mm Hg and 5 L/min, 100 mm Hg). Then, stability of the
      spinning motion was investigated by evaluating the vibration of the pump. The two
      pumps with different female pivots were operated identically at 2,700 rpm, and
      the vibration signals were measured using an accelerometer that was mounted on
      the top of the pump housing. The following findings were obtained in this study.
      The wear sites were different between the PE and CRM. Most of the wear occurred
      at the top female polyethylene pivot in the PE. In contrast, most of the wear
      occurred at the top male ceramic pivot in the CRM. In addition, the amount of the
      initial wear was less and the wear rate was lower in the PE than in the CRM. The
      hemolysis caused by the PE was less than the hemolysis caused by the CRM. The
      vibration signals of the PE had less amplitude and a narrower range of frequency
      than the vibration signals of the CRM. In conclusion, the combination of
      materials male ceramic-female polyethylene are superior to the male ceramic
      female ceramic for the double pivot bearing system of the Gyro C1E3 centrifugal
      pump because of less vibration, less hemolysis, and less wear.

PMID- 9028498
TI  - Effects of self washout structure on the antithrombogenicity and the hemolytic
      properties of a centrifugal pump.
AB  - Antithrombogenicity in an initial type (N1) of a centrifugal pump (CP) developed
      in our institute is provided by the central balancing hole of an impeller. A new
      CP (N2) was modified to obtain better antithrombogenicity, in which the balancing
      hole was widened to improve self washout flow velocity (Vsf), and an edge of the
      thrust bearing was rounded off to minimize flow separation. Effects of the
      modifications were assessed in vitro and in vivo studies. The Vsf of the N1 and
      the N2 evaluated by a Doppler velocimeter were 12.8 and 22.1 cm/s, respectively.
      Flow around the thrust bearing, which was visualized by a light cutting method,
      confirmed less flow stagnation in the N2. The hemolytic indices of the N1 and the
      N2 were 0.023 and 0.008 mg/dl, respectively. In vivo antithrombogenicity and the
      hemolytic properties of the N2 and the N1 were investigated without
      anticoagulation therapy in 3 goats. In each goat the N2 was driven for 1 week and
      exchanged for the N1, which was driven for the same period. Red thrombi at the
      thrust bearing were found in 2 N1s, and 2 small thrombi were on the impeller of
      another N1, whereas a thrombus of less than 1 mm3 at the TB was noted in 1 N2.
      Plasma free hemoglobin was not increased in either CP. These results indicate
      that the N2 has better antithrombogenicity and hemolytic properties than the N1.

PMID- 9028499
TI  - Do sheep really have problems with cardiopulmonary bypass for total artificial
      heart implantation?
AB  - Although the use of sheep in total artificial heart (TAH) implantation has many
      advantages, they are known to show a significant morbidity rate on
      cardiopulmonary bypass (CPB); this has been considered to be a major limiting
      factor in using them for TAH experiments. We conducted a series of ovine CPB
      experiments to evaluate the sheep's pathophysiological response to CPB. CPB
      related hemolysis, bleeding, and lung dysfunction were analyzed in 5 sheep, which
      had undergone CPB, used at our hospital for TAH implantation. Four of the 5 sheep
      survived the experimental procedures, and 3 of them survived on a long-term
      basis. Unacceptable degrees of hemolysis related to CPB were not observed.
      Postoperative bleeding was not remarkable, and coagulation test results did not
      show significant abnormal findings. Acute lung injuries of a mild to moderate
      degree were found mainly at the microscopic level, but rarely had clinical
      significance. In conclusion, this experiment suggests that sheep can be used for
      the animal model for TAH implantation with acceptable risk on CPB circuits and
      techniques are used.

PMID- 9028501
TI  - Generation of nitrate during dialysis as a measure of nitric oxide synthesis.
AB  - Nitric oxide (NO) is a recently identified messenger, which influences the local
      regulation of blood flow and platelets as well as neuronal and inflammatory
      pathways. Disturbed NO information might be involved in the uremic syndrome and
      might also cause hypotension during dialysis. To clarify these issues, we
      analyzed plasma and dialysis fluid concentrations of nitrate, the stable NO
      metabolite, in 9 patients during hemodialysis. Plasma nitrate was raised at the
      onset of dialysis as compared with healthy subjects (83 +/- 9 versus 26 +/- 2
      mumol/L). The plasma concentration decreased to 20 +/- 2 mumol/L (p < 0.01)
      during the dialysis. The relative decrease was more pronounced than the relative
      reduction in creatinine, phosphate, and urea concentrations. A parallel decrease
      in nitrate was seen in effluent dialysis fluid (32 +/- 4 to 14 +/- 1 mumol/L; p <
      0.01). Calculations of the amount of nitrate coming to and from the dialyzer were
      performed in 7 of the 9 patients, and in 5 of the 7 patients, generation of
      nitrate within the dialyzer could be postulated. This might explain the
      paradoxical venodilation noted during hemodialysis.

PMID- 9028502
TI  - Hot-knife dissection of the latissimus dorsi muscle for dynamic cardiomyoplasty.
AB  - The overall purpose of circulatory assistance utilizing skeletal muscle is the
      most efficient application of muscle power. From the histological viewpoint, hot
      knife dissection of the latissimus dorsi muscle (LDM) is presented to preserve
      muscle tissue. The shaw hemostatic scalpel could be used similarly to standard
      surgical blades, and its hemostatic performance was efficient in sealing
      collateral vessels from the thoracic wall. Muscular and nervous twitching was
      never observed throughout dissecting the LDM. Histological findings revealed that
      muscle fibers could be preserved by hot-knife dissection rather than by
      electrocautery. This technique may reduce the inconvenience of the operators,
      and, therefore, shorten the operation time in dynamic cardiomyoplasty and other
      experiments.

PMID- 9028500
TI  - A novel method to evaluate thromboresistance of drip chambers with filter used in
      extracorporeal blood circuits for hemodialysis.
AB  - We have developed a novel method to simultaneously evaluate thromboresistance of
      two different types of drip chambers with a filter used in extracorporeal blood
      circuits for hemodialysis using canine arteriovenous shunt models. Bilateral
      bypasses between the femoral artery and vein on both sides of the animal were
      formed with 2 test circuits consisting of polyvinyl chloride tubing and two types
      of drip chambers with filters. Blood flow was derived into the drip chambers with
      a filter and returned to the femoral vein without using peristaltic pumps and
      systemic anticoagulants. By monitoring the quantitative changes of the blood flow
      rate through each drip chamber with a filter and measuring the time elapsed
      before the blood flow through its was completely obstructed by clots,
      thromboresistance of the drip chambers was evaluated under the same blood
      conditions. The drip chamber with a filter that had a small effective filter
      area, a big pore size, and slitlike pores showed better thromboresistance. This
      novel method proved useful in evaluating the thromboresistance of differently
      designed drip chambers with a filter.

PMID- 9028504
TI  - Do we need health departments?

PMID- 9028503
TI  - Working pressure for full balloon inflation during intraaortic balloon pumping.
AB  - With changes in heart rate and mean aortic pressure, an intraaortic balloon (IAB)
      works with incomplete inflation. The effects of initial peak positive pressure
      and plateau holding positive pressure on IAB volume were investigated and minimum
      pressures necessary to inflate an IAB to a desired volume were established with a
      standard IAB catheter (Datascope type, 9.5 Fr, 40 ml). Initial peak pressure
      greater than 200 mm Hg was adequate to attain the desired volume of the IAB.
      Plateau positive pressure should be altered in accordance with hemodynamic
      changes.

PMID- 9028505
TI  - Antiproteinase deficiency, emphysema and replacement therapy.

PMID- 9028506
TI  - Survey of cyclosporin-sparing agent use in Australasian transplant centres.
AB  - BACKGROUND: The co-prescription of drugs which elevate cyclosporin blood
      concentration has been advocated to reduce the costs associated with use of this
      expensive immunosuppressive drug. This is the first time that drugs have been
      widely prescribed for an economic purpose and while it is thought to be
      widespread, there are little published data on the extent of this practice in
      Australia and New Zealand. AIMS: To determine the extent to which cyclosporin
      sparing agents are used by Australian and New Zealand organ transplant centres,
      to determine which agents are used and why these agents are used by some but not
      all centres. METHODS: Organ transplant centres were surveyed via a questionnaire.
      RESULTS: Considerable variation in use of cyclosporin sparing agents exists both
      within and across organ transplant types by Australian and New Zealand transplant
      centres. Diltiazem use is more widespread than ketoconazole. CONCLUSIONS: Little
      of the variability in use of cyclosporin sparing agents can be explained by
      scientific considerations. While the central government benefits from the
      significant cost savings achieved by the use of cyclosporin sparing agents,
      individual transplant units may not. Transplant units may however be the major
      target in the event of litigation arising as a result of adverse effects. The
      availability of generic brands and improved formulations of cyclosporin may
      affect the viability of using cyclosporin sparing agents.

PMID- 9028507
TI  - Epidemiological study of angioedema and ACE inhibitors.
AB  - BACKGROUND: Angioedema is an uncommon and poorly recognised adverse reaction to
      angiotensin converting enzyme inhibitors (ACE-Is). The epidemiology of this
      association has not been described. AIMS: To examine the epidemiology of
      angioedema and its relation to ACE inhibitor prescribing. To examine the
      characteristics of angioedema occurring in patients taking ACE inhibitors.
      METHODS: A retrospective case control study and a case note audit were conducted
      of 40 patients who presented to a teaching hospital Accident and Emergency
      Department with angioedema on 48 occasions. One hundred and sixty control
      subjects presenting to the same Accident and Emergency Department but without
      angioedema were matched to cases by age, sex and presentation date. An ecological
      study comparing the numbers of angioedema admissions by age cohorts to South
      Australian (SA) public hospitals with the prescription volumes of ACE-Is in
      Australia was also undertaken. RESULTS: Case control study: In patients
      presenting with angioedema compared with controls, the exposure odds ratio for
      ACE-Is was 5.1 (95% CI 2.03-12.89) and for non-steroidal anti-inflammatory drugs
      (NSAIDs) was 4.13 (95% CI 1.28-13.39). CASE NOTE AUDIT: 15/40 (38%) patients
      presenting with angioedema on 19/48 (40%) occasions were taking an ACE-I. These
      patients were older and less likely to have an atopic history than those not
      taking an ACE-I. The onset of angioedema after starting an ACE-I was delayed for
      greater than six months in nine patients. ACE-I therapy was continued after 53%
      of presentations. ECOLOGICAL STUDY: The number of admissions with angioedema to
      SA public hospitals increased between 1985-86 and 1994-95, predominantly in older
      patients, and paralleled the increasing prescription volumes of ACE-Is.
      CONCLUSIONS: A considerable proportion of patients presenting with angioedema
      will be taking an ACE-I or a NSAID. The association of ACE-Is and angioedema is
      not well recognised, partly because the onset of angioedema may be delayed for
      months or years after commencement of an ACE-I. A persisting risk of angioedema
      is present in patients who have initially commenced an ACE-I uneventfully. The
      epidemiology of angioedema is now changing in parallel with the increasing use of
      ACE-Is.

PMID- 9028508
TI  - Symptomatic human immunodeficiency virus (HIV) infection in Papua New Guinea.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) infection was first detected in
      Papua New Guinea (PNG) in 1987. By August 1995 a total of 323 persons had been
      diagnosed as HIV antibody positive nationwide and seroprevalence rates were
      climbing. This study was prompted by a lack of data on the clinical syndromes
      associated with HIV infection in Melanesian adults. AIMS: To describe the
      clinical and epidemiological features of symptomatic HIV infection in adult
      Melanesians. METHODS: A largely retrospective study of patients was admitted to
      the medical wards of the Port Moresby general hospital between January 1990 and
      September 1995. Clinical records of patients with antibody to HIV were studied
      and clinical, laboratory and epidemiological data were recorded. RESULTS: Seventy
      patients were studied and the majority were young, urban dwelling adults from a
      variety of social groups. The sex distribution was even. Common clinical
      syndromes associated with HIV infection were chronic diarrhoea (47.8%), wasting
      (94.2%) and oropharyngeal candidiasis (68.7%). Tuberculosis was suspected in
      68.6% and cryptococcal meningitis was detected in 8.6% including one patient with
      Cryptococcus. neoformans var. gattii infection. There was a high mortality (53%)
      in patients admitted to hospital. CONCLUSIONS: Patients with HIV infection in PNG
      present to hospital late in their disease course. Clinical syndromes are similar
      to those observed in Africa and mortality on first admission is high. The major
      mode of transmission is heterosexual and sexually transmitted diseases and
      promiscuity are probably important factors in facilitating spread.

PMID- 9028509
TI  - Hepatitis C genotypes in Australian haemophilia patients.
AB  - BACKGROUND: Differences in the hepatitis C virus (HCV) genotype influence the
      severity of HCV related liver disease and response to interferon therapy. HCV
      infection is frequent in Australian haemophilia patients who have been exposed
      repeatedly to multiple HCV genotypes through non HCV virally inactivated clotting
      factor concentrates. The distribution of the various HCV genotypes in Australian
      haemophilia patients is unknown. AIM: To examine the HCV genotype distribution
      and clinical features of HCV associated liver disease in Australian haemophilia
      patients. METHODS: Forty patients with bleeding disorders who were known to be
      both HCV antibody and polymerase chain reaction (PCR) positive were evaluated by
      direct sequencing of the PCR products for the HCV genotype. RESULTS: Genotype 1
      was found in 65% of patients (26/40), type 2 in 5% (2/40) and type 3 in 30%
      (12/40). No genotypes 4 to 6 were found. There was no association between the HCV
      genotype and the severity of haemophilia, alanine transaminase levels, or the
      presence of portal hypertension. Unlike European, Asian and American studies
      where the majority of type 1 infection is subclass 1b, in Australian haemophilia
      patients it is subclass 1a (73%-19/26) which may have a better prognosis and
      response to interferon. CONCLUSIONS: Despite patients with haemophilia being
      exposed to multiple HCV genotypes, it appears that there is no selection
      advantage of one genotype over another. Australian haemophilia patients with HCV
      have a different genotype distribution to that reported in other countries and
      care should be observed in interpreting non Australian studies concerning HCV.

PMID- 9028510
TI  - A prospective study of the gastroenterological causes of iron deficiency anaemia
      in a general hospital.
AB  - BACKGROUND: Current practice is to investigate routinely both upper and lower
      gastrointestinal tracts in patients with unexplained iron deficiency anaemia.
      AIMS: To determine the efficacy of this approach and whether the use of more
      stringent biochemical criteria for iron deficiency, symptoms, or a positive
      immunochemical faecal human haemoglobin (FHH) influenced the findings of the
      investigations and could help target investigations more efficiently. METHODS:
      Eighty patients were studied prospectively, 51 who had "definite' iron deficiency
      anaemia (low ferritin and transferrin saturation) and 29 with "probable' iron
      deficiency anaemia (either low ferritin or transferrin saturation). Patients
      underwent a standardised symptom assessment and testing for FHH, upper endoscopy
      with small bowel biopsy and colonoscopy, and a small bowel series if upper
      endoscopy and colonoscopy were negative. RESULTS: Lesions potentially causative
      for iron deficiency anemia were found in 54/80 (60%) of patients. Five patients
      (7%) had lesions in both upper and lower tracts. Small bowel biopsy was abnormal
      in one of 80 patients and small bowel series one of 25 patients. Significant
      lesions in either the upper or lower gastrointestinal tract were found in 14/20
      patients with positive FHH and 25/47 with negative FHH. Symptoms, use of non
      steroidal anti-inflammatory drugs and classification of patients into "definite'
      and "probable' iron deficiency did not influence yield of investigations or site
      of lesions found. CONCLUSIONS: Gastrointestinal lesions are common in patients
      with unexplained iron deficiency anaemia. Neither symptoms nor presence of FHH
      predict the presence of site of detectable lesions and neither testing for FHH
      nor more stringent biochemical criteria for iron deficiency alters clinical
      decision making. The findings support the routine performance of both upper
      endoscopy and colonoscopy in the investigation of patients with unexplained iron
      deficiency anaemia, however routine investigation of the small bowel is of
      questionable value.

PMID- 9028511
TI  - A comparison of the effects of oral prednisone and inhaled beclomethasone
      dipropionate on circulating leukocytes.
AB  - BACKGROUND: While the side effects of oral glucocorticoids are well recognised
      there is debate about the systemic effects of high doses of inhaled
      glucocorticoids such as beclomethasone dipropionate and how these compare with
      the effects of oral prednisone. AIMS: To compare the effects of different doses
      of oral prednisone and inhaled beclomethasone dipropionate (BDP) on changes in
      circulating leukocytes. METHODS: Changes in different subsets of circulating
      leukocytes were measured as an index of the systemic effects of inhaled BDP and
      oral prednisone. We compared the effects of inhaled placebo and 500 and 1000
      micrograms of inhaled BDP with oral placebo and 2.5, 5 and 10 mg of prednisone in
      eight healthy volunteers. Leukocyte numbers were measured before and four hours
      after each dose of medicine. RESULTS: Compared with inhaled placebo, 1000
      micrograms of inhaled BDP led to a significant increase in neutrophils as a
      percentage of the total white count (p < 0.05) and a significant decrease in the
      total lymphocyte number (p < 0.05) and in the number of CD4 lymphocytes (p <
      0.05). For 1000 micrograms BDP the increase in the % neutrophil count was 8.55%
      (95% CI 5.17 to 11.93) and the fall in lymphocyte numbers was -0.14 x 10(9)/L
      (95% CI 0.06 to -0.34) while 2.5 mg prednisone led to an increase in the %
      neutrophil count of 9.31% (95% CI 5.82 to 12.80) and a fall in lymphocyte numbers
      of -0.07 x 10(9)/L (95% CI 0.05 to -0.19). CONCLUSIONS: The systemic effects of
      1000 micrograms inhaled BDP and 2.5 mg of prednisone are similar.

PMID- 9028512
TI  - Comparison of optimised planar scintigraphy with SPECT thallium, exercise ECG and
      angiography in the detection of coronary artery disease.
AB  - BACKGROUND: Thallium SPECT has been shown to be more sensitive than planar
      imaging in the detection of coronary heart disease (CAD) in a number of reported
      series. Early (< 10 minutes) redistribution on planar imaging has been
      demonstrated in clinical studies and this may partly contribute to its lower
      sensitivity. AIM: To determine whether thallium SPECT is superior to planar
      scintigraphy (with the timing of imaging performed optimally so that it was
      commenced within five minutes of injection) in the detection of CAD. METHODS:
      Planar and SPECT studies were performed in 44 patients with significant (> 70%
      stenosis) CAD, seven patients with borderline stenoses (50-69%) and in 18
      patients with no significant CAD. RESULTS: The sensitivity of planar imaging was
      66% which was higher than exercise ECG 54% (ns) but significantly lower than
      SPECT 86% (p < 0.005). The specificity of planar thallium scintigraphy was 100%
      which was higher than SPECT (83%) and significantly higher than exercise ECG 72%
      (p < 0.05). SPECT had a significantly higher sensitivity for LAD and single
      vessel disease than planar imaging and this was unrelated to a history of prior
      myocardial infarction. CONCLUSION: Even when planar imaging is timed optimally to
      minimise the impact of early redistribution, SPECT is more sensitive than either
      planar imaging or exercise ECG in the detection of CAD, but its specificity is
      lower.

PMID- 9028513
TI  - G-CSF stimulated donor granulocyte collections for prophylaxis and therapy of
      neutropenic sepsis.
AB  - BACKGROUND: The administration of granulocyte colony-stimulating factor (G-CSF)
      increases the granulocyte count in normal donors and enables the collection of
      large numbers of mature myeloid cells by leukapheresis. This has potential value
      in the treatment of sepsis unresponsive to antibiotics in patients with severe
      neutropenia. AIM: To evaluate the tolerability of granulocyte collections in
      normal donors receiving G-CSF, the optimal method of collection and the clinical
      factors influencing the efficacy of granulocyte infusions. METHODS: Analysis of
      the outcome of 55 granulocyte collections from 26 donors for progressive
      bacterial or fungal sepsis in neutropenic patients (n = 8) or as prophylaxis in
      patients with recent fungal infections undergoing allogeneic bone marrow
      transplantation (BMT) (n = 3). RESULTS: G-CSF was well tolerated in most donors.
      Fatigue occurred commonly after the second collection. The median WCC per 200-220
      mL bag was 351 x 10(9)/L. Collections were optimised with the use of a
      sedimenting agent (dextran) and a deepened interface setting on the cell
      separator. There was only a weak correlation between the number of granulocytes
      infused and the increment in the patient, but levels were usually maintained > or
      = 0.5 x 10(9)/L for the next 24 hours. The infusions were successful in three
      septic patients without multi-organ dysfunction and prophylactically, in two
      patients with localised fungal infections undergoing MBT. The infusions were not
      beneficial in patients with septicaemia and established organ dysfunction or with
      extensive pulmonary aspergillosis. CONCLUSIONS: G-CSF mobilised granulocyte
      collections are feasible and the preliminary evidence suggests that the infusion
      of these cells may be useful early in the prophylaxis or treatment of severe
      neutropenic sepsis.

PMID- 9028514
TI  - Update in eating disorders.

PMID- 9028515
TI  - ABO incompatible renal transplantation: a chance to re-examine?

PMID- 9028517
TI  - The long QT syndromes.

PMID- 9028516
TI  - Exercise and insulin-dependent diabetes mellitus (IDDM): benefits and pitfalls.

PMID- 9028518
TI  - Is it diabetes mellitus or Munchausen's syndrome?

PMID- 9028519
TI  - Left main coronary artery stenting under extracorporeal circulatory support.

PMID- 9028520
TI  - Emotional incontinence: a dramatic response to paroxetine.

PMID- 9028521
TI  - A lethal pedigree of hypertrophic cardiomyopathy associated with mild left
      ventricular hypertrophy.

PMID- 9028522
TI  - Acute interatrial right to left shunt causing life threatening hypoxia following
      surgery.

PMID- 9028523
TI  - Twenty-four-hour urine analysis in patients with orthostatic hypotension and
      chronic fatigue syndrome (CFS)

PMID- 9028524
TI  - Coeliac disease and familial hypercholesterolaemia.

PMID- 9028525
TI  - Pulmonary hypertension as a consequence of alveolar capillary plugging by
      malignant megakaryocytes in essential thrombocythaemia.

PMID- 9028526
TI  - Vomiting--a forgotten symptom in thyrotoxicosis.

PMID- 9028527
TI  - Recurrent Legionella longbeachae pneumonia associated with re-exposure to potting
      soil?

PMID- 9028528
TI  - Silicone? Silica? Scleroderma. A need to look further?

PMID- 9028529
TI  - Erythropoietin treatment for postural hypotension from autonomic dysfunction.

PMID- 9028530
TI  - Localization of cathepsin K in human osteoclasts by in situ hybridization and
      immunohistochemistry.
AB  - We have recently cloned cathepsin K from a human bone cDNA library. Since
      cathepsins are proposed to be involved in the degradation of mineralized bone
      matrix, we have investigated, by in situ hybridization and immunocytochemistry,
      the expression of the cathepsin K mRNA transcripts and protein in sections of
      bone and giant cell tumor to determine which cells express this enzyme. Within
      all tissues studied, cathepsin K was highly expressed in osteoclasts.
      Furthermore, the expression of cathepsin K mRNA in giant cell tumor tissue
      appeared to be confined to the periphery of the osteoclast indicating a
      compartmentalization of the mRNA. Immunohistochemistry confirmed the specific
      localization of cathepsin K to the osteoclast. In actively resorbing osteoclasts,
      the immunostaining was localized at the ruffled border, whereas in osteoclasts in
      sections of giant cell tumor, staining was observed in lysosomal vacuoles, which
      in some cases were seen to fuse with the cell membrane. Other cells within the
      bone, such as osteoblasts and osteocytes, did not express either the cathepsin K
      transcript or protein. However, there were very low levels of cathepsin K
      detected in a population of mononuclear cells, possibly representing osteoclast
      progenitor cells, within the marrow/stromal layer. The specific localization of
      cathepsin K within osteoclasts would therefore indicate the potential role of
      this enzyme in the bone resorptive process.

PMID- 9028531
TI  - Demonstration of estrogen receptor mRNA in bone using in situ reverse
      transcriptase polymerase chain reaction.
AB  - Falling estrogen levels affect the female skeleton profoundly. Following
      menopause, estrogen lack is a major cause of osteoporosis. The site of estrogen
      action in human bone, however, is unclear, but responsive cells must express the
      estrogen receptor (ER). One obstacle to localizing these cells is that mRNA for
      ER is expressed in low copy number. Hence, conventional molecular techniques are
      either too insensitive to detect receptor transcripts (in situ hybridization) or
      necessitate amplification of RNA extracted from tissue [Northern analysis and
      polymerase chain reaction (PCR)], thus failing to identify the specific target
      cells within the mixed-cell population of bone. In situ PCR (IS-PCR) is a
      technique that combines the sensitivity of PCR with the localization of
      conventional in situ hybridization. The technique has previously been used
      primarily to detect single-copy genes and viral DNA within cells. More recently,
      incorporation of a reverse-transcriptase reaction (IS-RT-PCR) has allowed the
      technique to be used to identify rare mRNAs within tissues. We have therefore
      applied the technique of IS-RT-PCR to localize ER mRNA first in human breast
      tumors, a known positive tissue, and then in bone. Using conventional riboprobe
      in situ hybridization, ER transcripts were not detectable in any bone cells
      within sections taken from normal bone and several actively remodeling bone
      tissues, namely, Paget's disease, renal hyperparathyroidism, and healing fracture
      callus. The technique of IS-RT-PCR, however, allowed amplification of transcripts
      to a detectable level. Following two cycles of amplification, hybridization
      signal was observed in osteoblasts and to a lower level in osteoclasts and
      occasional osteocytes. This positive signal was more obvious after five cycles,
      particularly in osteoclasts and osteocytes. After ten cycles, although signal was
      increased in osteoclasts and osteocytes, it appeared to be decreased in
      osteoblasts, suggesting that overamplification leads to loss of target complex
      from these cells. We conclude that several cell types in human bone express ER
      mRNA in vivo.

PMID- 9028533
TI  - Osteogenesis by bone marrow stromal cells maintained on type I collagen matrix
      gels in vivo.
AB  - In this study, we demonstrated that bone marrow stromal cells maintained on type
      I collagen matrix induced bone in vivo. The formed bone contained bone marrow,
      and the process of bone formation occurred without cartilage formation. Bone
      marrow stromal cells differentiated into osteoblasts on type I collagen matrix in
      vitro, but types II, III, and V collagens did not possess this activity. These
      findings imply that type I collagen matrix offers a suitable environment for the
      induction of osteoblastic differentiation in vitro and osteogenesis in vivo.

PMID- 9028532
TI  - Proliferating cells in the primary spongiosa express osteoblastic phenotype in
      vitro.
AB  - We have shown that intermittent parathyroid hormone (PTH) treatment targets
      proliferating cells in the primary spongiosa of trabecular bone of young rats,
      resulting in an increased number of osteoblasts. To further characterize these
      proliferating osteoprogenitor cells, bromodeoxyuridine (BrdUrd) incorporated in
      vivo, was used as a marker to identify and isolate cells for in vitro studies.
      Proliferating cells were labeled in vivo in young rats with BrdUrd and 24 h later
      were isolated by trypsinization of sections of the primary spongiosa of the
      distal femur metaphysis. Within 12 h of isolation, BrdUrd+ cells formed distinct
      foci containing 20-500 cells with fibroblast morphology. Stimulation of
      proliferation as determined by [3H]-thymidine incorporation was observed for
      these cells in response to fetal bovine serum, platelet derived growth factor,
      and transforming growth factor beta-1. Neither insulin-like growth factor-1 (IGF
      1) nor insulin stimulated proliferation PTH (1-34) and dexamethasone inhibited
      proliferation. The effects of PTH and dexamethasone were additive. Cells
      expressed the osteoblast phenotype as evidenced by synthesis of type I collagen,
      expression of high alkaline phosphatase activity, and production of increased
      intracellular cAMP in response to PTH (1-34). Confluent cell aggregates
      spontaneously formed mineralized nodules within 4-7 days, in the absence of
      inducers. These observations suggest that the primary spongiosa cells
      recapitulates the differentiation process in vitro in an accelerated fashion and
      may serve as a useful model to study osteoblast differentiation.

PMID- 9028534
TI  - Demonstration of feasibility of automated osteoblastic line culture in space
      flight.
AB  - There is a large body of evidence that microgravity- or immobilization-induced
      bone loss is mainly related to osteoblastic cell impairment. Osteoblasts are
      sensitive to increased mechanical stress and could therefore be responsible for
      unloading-induced bone changes. However, the nature of osteoblast involvement
      remains unclear. The effects of the space environment on cells have been studied
      extensively, but little information about anchorage-dependent cell cultures of
      the 25 different cell types flown in space has been published. We studied the
      effects of long-term weightlessness on the cell shape of cultured osteoblasts
      during the Russian Bion 10 space-flight. This experiment required the development
      of special automatic culture devices (the plunger-box culture system) finalized
      with the constructors. Multiple feasibility experiments were performed to allow
      osteoblast culture for 6 days in microgravity. The study revealed plunger-box
      biocompatibility; optimization of ROS 17/2.8 (mammalian adherent cells) culture
      under closed conditions (without gas exchange); and transport of viable cells for
      5 days. During the 6 days of microgravity, the growth curves of ground controls
      and cells in space were roughly similar. Alkaline phosphatase activity was
      enhanced twofold in microgravity. ROS 17/2.8 cell morphology began to change
      significantly after 4 days of microgravity; they became rounder and covered with
      microvilli. At the end of the flight, the cells exhibited mixed morphological
      types, piling cells, stellar shape, and spread out cells, resembling ground
      controls or 1g flight controls (centrifuge). We demonstrated that ROS 17/2.8
      cells were viable during a 6 day automatic culture in space and were sensitive to
      space related conditions. They adapted their structure and function to this
      environment, characterized by loss of mechanical stimuli.

PMID- 9028535
TI  - Expression of bone associated markers by tooth root lining cells, in situ and in
      vitro.
AB  - Periodontal disease is marked by inflammation and subsequent loss and/or damage
      to tooth-supporting tissues including bone, cementum, and periodontal ligament. A
      key tissue in the initial process of periodontal development as well as
      regeneration following periodontal disease is cementum. Research efforts aimed
      toward understanding mechanisms involved in periodontal development and
      regeneration, and in particular the formation of root cementum, have been
      hampered by an inability to isolate and culture cells involved in cementum
      production (i.e., cementoblasts). Much has been learned regarding the processes
      and mechanisms involved in bone formation and function from experiments using
      bone cell cultures. Therefore, the purpose of this study was to develop a
      strategy whereby cementoblasts could be isolated, cultured, and characterized. As
      a first step, using in situ hybridization, we determined the timed and spatial
      expression of mineral-associated proteins during first molar root development in
      CD-1 mice. These proteins included dentin sialoprotein (DSP), osteopontin (OPN),
      bone sialoprotein (BSP), osteocalcin (OCN), and type I collagen. During root
      development in mice BSP, OPN, and OCN mRNAs were expressed selectively by cells
      lining the tooth root surface--cementoblasts--with high levels of expression at
      day 41. Importantly, at this time point BSP, OPN, and OCN mRNAs were not
      expressed throughout the periodontal ligament. These findings provided us with
      markers selective to root-lining cells, or cementoblasts, in situ, and
      established the time (day 41) for isolating cells for in vitro studies. To
      isolate cells from tissues adherent to the root surface, enzymatic digestion was
      used, similar to what are now considered classical techniques for isolation of
      osteoblasts. To determine whether cells in vitro contained root-lining cells and
      cementoblasts, cultured cells were analyzed for expression of mineral-associated
      proteins. Cells within this heterogeneous primary population expressed type I
      collagen, BSP, OPN, and OCN as determined by in situ hybridization. In contrast,
      cells within this population did not express dentin sialoprotein, an odontoblast
      specific protein. These procedures have provided a means to obtain root-lining
      cells in vitro that can now be cloned and used for studies directed at
      determining the properties of root-lining cells, or cementoblasts, in vitro.

PMID- 9028536
TI  - Alteration of mineral crystallinity and collagen cross-linking of bones in
      osteopetrotic toothless (tl/tl) rats and their improvement after treatment with
      colony stimulating factor-1.
AB  - A common feature of various types of mammalian osteopetroses is a marked increase
      in bone mass accompanied by spontaneous bone fractures. The toothless (tl/tl) rat
      osteopetrotic mutation is characterized by drastically reduced bone resorption
      due to a profound deficiency of osteoclasts and their precursors. An altered bone
      morphology has also been observed. The mutants cannot be cured by bone marrow
      transplantation, but skeletal defects are greatly reduced after treatment with
      colony stimulating factor 1 (CSF-1). The objectives of this study were to
      characterize mineral and collagen matrices in cancellous and compact bone
      isolated from long bones of 6-week-old normal littermates, tl/tl osteopetrotic
      mutants and mutants (tl/tl) treated with CSF-1. There were no differences in bone
      mineral content, but a significant decrease in the crystallinity of mineral
      evaluated by the method based on electron paramagnetic resonance spectrometry was
      observed in all bones of tl/tl mutants as compared to that of controls. Within
      the collagen matrix, slight decreases in the labile cross-links, but significant
      increases in the content of the stable cross-links, pyridinoline, and
      deoxypyridinoline, were observed in both cancellous and compact bone of
      osteopetrotic mutants. In tl/tl mutants treated with human recombinant CSF-1, the
      normalization of the crystallinity of bone mineral as well as collagen cross
      links was found. Our results indicate that remodeling of bone matrix in tl/tl
      mutants is highly suppressed, but that after treatment with CSF-1, this activity
      recovers significantly. Taken together, these data provide further support for
      the hypothesis that CSF-1 is an essential factor for normal osteoclast
      differentiation and bone remodelling.

PMID- 9028537
TI  - Collagen formation and degradation increase during growth hormone therapy in
      children.
AB  - A comprehensive set of serum markers of collagen turnover and growth was
      investigated in a longitudinal study of short children during growth induced by
      growth hormone (hGH) treatment. The study comprised 18 prepubertal children with
      short stature who had no other current illness or continuous medication. The
      growth rates and endogenous GH secretions covered a continuum from subnormal to
      normal. Before treatment, the concentrations of carboxyterminal propeptide of
      type I procollagen (PICP), reflecting type I collagen formation, of
      carboxyterminal telopeptide of type I collagen (ICTP), a degradation product of
      type I collagen, of amino-terminal propeptide of type III procollagen (PIIINP), a
      marker for type III collagen formation, of alkaline phosphatase (AP), and of
      insulin-like growth factor binding protein-3 (IGFBP-3) were within the lower
      limits of normal. The median IGF-I concentration was lower than the reference.
      One week after the start of treatment, the serum concentrations of ICTP, PIIINP,
      and osteocalcin (OC), and the increments in ICTP, PIIINP, and IGF binding protein
      3 (IGFBP-3) correlated with the subsequent height velocity. During the 12-month
      treatment, all markers were higher than those of age-matched references, but only
      the three collagen markers paralleled the changes in height velocity. In molar
      concentrations, ICTP increased less than PICP. Throughout the study period, the
      serum level of ICTP correlated with that of PIIINP, but not with that of PICP.
      The findings suggest that during hGH treatment, linear body growth is closely
      associated with collagen formation and degradation.

PMID- 9028538
TI  - Very low rate of type I collagen synthesis and degradation in newly diagnosed
      children with acute lymphoblastic leukemia.
AB  - In children with acute lymphoblastic leukemia (ALL), the metabolism of type I
      collagen, the major collagen of bones, may be changed at diagnosis and during
      early chemotherapy. In the present study, bone formation and degradation rates
      were evaluated longitudinally in 35 children with ALL, using two serum markers of
      bone collagen formation: the amino-terminal (PINP) and carboxyterminal (PICP)
      propeptides; and a marker of degradation: the carboxyterminal telopeptide of type
      I collagen (ICTP). These serum markers were determined at diagnosis, during
      induction treatment (at 1, 4, and 6 weeks), and during consolidation treatment
      (at 8 and 12 weeks). The changes in the serum markers suggested that, at
      diagnosis, type I collagen turnover (i.e., both synthesis and degradation) was
      remarkably low. The median serum levels of PINP, PICP, and ICTP were -2.6 SDS
      (standard deviation score), -1.5 SDS, and -2.5 SDS, respectively. The PICP and
      PINP levels declined further during the first week of therapy (p < 0.001),
      whereas the ICTP levels had risen by end of the induction phase (p < 0.05). By
      the end of the 12 week interval, the concentrations of the formation and
      degradation markers had returned to normal (p < 0.01). Our findings suggest that
      ALL is accompanied by low turnover of bone collagen. The abnormalities are at
      first aggravated, but then corrected, by treatment.

PMID- 9028539
TI  - The influence of family history of hip fracture on the risk of vertebral
      deformity in men and women: the European Vertebral Osteoporosis Study.
AB  - There are few data exploring clustering of osteoporotic fractures within
      families. The aim of this study was to determine the influence of maternal and
      paternal history of hip fracture on the risk of vertebral deformity. 12,816 men
      and women aged 50 to 75 years were recruited from population based sampling
      frames across Europe. Subjects were invited to attend by letter of invitation for
      an interviewer administered questionnaire and lateral spinal radiographs.
      Vertebral deformity was defined morphometrically using the McCloskey-Kanis
      method. 6.4% of men and 7.1% of women reported that their mother had suffered a
      hip fracture, while 1.7% of both men and women reported that their father had
      suffered a hip fracture. A maternal history of hip fracture was associated with a
      modest increased risk of vertebral deformity in men [odds ratio (OR) 1.3, 95%
      confidence interval (CI) 1.0-1.8], the risk being greater among those aged 65
      years and over (OR = 1.5; 95% CI 1.0-2.4) and in those from low prevalence areas.
      There was no increased risk in women. Paternal history of hip fracture was not
      associated with vertebral deformity in either sex. In conclusion, maternal
      history of hip fracture appears to be a risk factor for vertebral deformity,
      particularly in men.

PMID- 9028540
TI  - The response in spinal bone mass to tibolone treatment is related to bone
      turnover in elderly women.
AB  - To determine the ability of bone turnover to predict the response in bone mass
      during treatment with Tibolone, two biochemical markers of bone metabolism were
      evaluated [CrossLaps corrected for urinary creatinine (CrossLaps/Cr.) and serum
      osteocalcin measured in a newly developed assay (N-Mid)]. Data from a 2-year
      double-blind, randomized trial with 56 completing Tibolone-treated women and 13
      placebo-treated women were studied. Bone mineral density in the spine (QDR-1000)
      and indices of bone turnover were determined every 3 months throughout the study.
      The response in bone mass was calculated as the percent annual change in bone
      mineral density from baseline and was determined from a total of nine
      measurements. The response in bone mass was correlated to prestudy values of
      CrossLaps/Cr. (r = 0.27; p < 0.05), but was uncorrelated to prestudy values of N
      Mid. The changes from baseline of these two markers were significantly correlated
      with the response in bone mass from the 6 months' time point and throughout the
      rest of the study, i.e., at 1 year: CrossLaps/Cr.: r = 0.54; p < 0.001, N-Mid: r
      = 0.49; p < 0.001). The change from baseline in the two markers was clearly more
      predictive of the response in bone mass than the baseline values of these markers
      as evaluated in a multiple, linear regression-model. Within 1 year of Tibolone
      treatment, measured changes in CrossLaps/Cr. and bone mineral density are at
      least equally predictive of the true response in bone mass over 2 years. These
      results indicate a possibility of monitoring Tibolone therapy with biochemical
      markers of bone turnover, at least on group basis.

PMID- 9028541
TI  - In vitro assessment of the relationship between acoustic properties and bone mass
      density of the calcaneus by comparison of ultrasound parametric imaging and
      quantitative computed tomography.
AB  - This in vitro study aimed to add new experimental evidence to clarify the
      relation between acoustic properties of bone and bone mineral density (BMD) of
      the human calcaneus. Parametric images of normalized broadband ultrasonic
      attenuation (nBUA) and ultrasound bone velocity (UBV) were compared with
      quantitative computed tomography (QCT) images of the calcaneus. The experimental
      protocol was designed to control the different potential sources of error in
      acoustic measurements, including the shape and thickness of the samples,
      intervening soft tissues and cortical bone, boundary effects, and variation in
      location of the regions of interest (ROIs) analyzed by ultrasound and X-ray. The
      present study was based on bone specimens from calcaneus removed from 15 cadavers
      (six male and nine female donors ranging from 69 to 89 years of age). Immersion
      ultrasonic measurements were performed in the through-thickness direction at
      normal incidence using a pair of focused broad-band 0.5-MHz transducers. QCT of
      the specimens was performed using standard 10-mm-thick slices with the Cann
      Genant calibration standard. Identical, site-matched ROIs were selected for
      quantitative analysis on the three images. The pattern of acoustic parameters was
      similar to that of BMD with QCT. The relationships between nBUA and BMD (r2 =
      0.75), between UBV and BMD (r2 = 0.88) and between nBUA and UBV (r2 = 0.84) were
      highly significant (p < 10(-4). From this study, it appears that ultrasound
      parameters as measured with current transmission techniques reflect mainly bone
      quantity and only reflect microarchitecture to a small extent and that BUA and
      UBV reflect the same bone property.

PMID- 9028542
TI  - Bone mineral density in normal Swedish women.
AB  - We examined 429 women, aged 20-80 years, randomly selected from the population
      register to establish normal values for bone mineral density (BMD) in Swedish
      women. BMD of the spine and hip was measured by dual-energy X-ray absorptiometry
      (DEXA; Hologic QDR 1000) and in the forearm by single photon absorptiometry (SPA;
      Molsgaard ND-1100). The recalled age of menarche was negatively correlated to BMD
      at all ages. There was no significant change in BMD from 20-49 years at any site
      except a slight decline at Ward's triangle. Bone loss was rapid at all sites
      during the first decade after menopause. Thereafter, BMD declined slowly in the
      trochanter and total hip but more rapidly in the forearm, femoral neck, and
      Ward's triangle. BMD in the spine even increased in the eighth decade probably
      due to osteoarthritis. The average change in forearm BMD during the 15
      perimenopausal years comprising mean age for menopause +/- 2 SD (43-57 years) was
      -0.4% per year in premenopausal females and -1.6% per year in postmenopausal
      females. The corresponding annual percental change was, for the spine, +0.2 and 
      1.7; neck, -0.7 and -1.7; trochanter, +0.5 and -1.5; and Ward's triangle, -0.1%
      and -2.2%, respectively. Our normal values for lumbar spine BMD prior to
      menopause did not differ from published values or the manufacturer's normal
      values; however, our spine BMD values for the first decade after menopause were
      significantly lower (approximately 10%) than in other studies. Our femoral neck
      BMD values for younger women were, like those of several other groups,
      significantly lower than the manufacturer's normal values, but our sample of
      young women in this study was small. The prevalence of osteoporosis, if defined
      as t score < -2.5 is highly dependent on the sampling of the reference population
      of young adult women, and also on the choice of skeletal site. Further studies on
      bone mineral density in healthy young adult women are needed.

PMID- 9028543
TI  - Lactose intolerance (LI) predisposes to reduced perimenopausal BMD.

PMID- 9028544
TI  - Additional myeloablation with 52Fe before bone marrow transplantation.
AB  - For many hematological malignancies, high-dose chemoradiotherapy followed by bone
      marrow transplantation offers the best and sometimes the only chance for cure.
      However, the main causes of failure of this therapy are relapse and toxicity. In
      order to selectively deliver higher doses of radiotherapy to the bone marrow and
      to spare normal organs, we explored 52Fe therapy before a conventional BMT
      conditioning regimen. Twenty-four patients at high risk for relapse after BMT
      were included in a phase II study. The median follow-up was 42 months. The median
      52Fe dose was 59 mCi. This resulted in a median radiation-absorbed dose (RAD) to
      the BM of 626 rad. The median RAD to the liver was 338 rad. No untoward effects
      were noted after the injections of 52Fe. The patients recovered hematopoiesis
      without toxicity in excess of that expected with conventional conditioning alone.
      The 3-year DFS probability was 49% (95% CI: 20-78%). Eight patients have
      relapsed, three of them in extramedullary sites. 52Fe should provide a way to
      boost the radiation dose to marrow-based diseases before bone marrow
      transplantation without excessive toxicity.

PMID- 9028545
TI  - Collection and use of peripheral blood stem cells in young children with
      refractory solid tumors.
AB  - Fifteen children 4 years of age or under (8-46 months), weight 7.8 to 17 kg,
      underwent 44 peripheral blood stem cell (PBSC) collections. Diagnoses included
      PNET/medulloblastoma (five), neuroblastoma (five), and others (five). PBSCs were
      collected following G-CSF/GM-CSF or chemotherapy plus G-CSF/GM-CSF mobilization.
      All PBSC collections were well tolerated. The average yield per collection was
      6.80 x 10(8) mononuclear cells/kg (1.1-30 x 10(8)/kg) or 57.60 x 10(6) CD34+/kg
      (1.37 to 480 x 10(6)/kg). Eight patients underwent stem cell transplantation
      following myeloablative chemotherapy. Six of the eight children who received PBSC
      following myeloablative therapy also received autologous bone marrow (0.7 to 3.6
      x 10(8) MNC/kg). One heavily pretreated patient experienced delayed hematologic
      reconstitution, while the remaining seven patients had a median ANC recovery to >
      0.5 x 10(3)/microliter by day +10 (9-11 days) and platelets > 50 x
      10(3)/microliter by day +15 (12-17 days). Seven patients received PBSCs following
      repetitive submyeloablative chemotherapy (ICE: ifosfamide 1.8 g/m2/day, etoposide
      100 mg/m2/day x 5, carboplatin 400 mg/m2/day x 2) or other similar combination
      chemotherapy. Median days to recover ANC > or = 1 x 10(3)/microliter and
      platelets > or = 100 x 10(3)/microliter in children receiving ICE + PBSCs were 10
      and 14 days, respectively, compared with 16 and 22 days in children receiving ICE
      + G-CSF in historical controls. In conclusion, collection and use of PBSCs to
      support either myeloablative chemotherapy or multicycle submyeloablative
      chemotherapy is well tolerated and may enhance hematological recovery in young
      children and infants.

PMID- 9028546
TI  - Application of an HLA-B PCR-SSOP typing method to a bone marrow donor registry.
AB  - A previously reported HLA-B PCR-SSOP typing method has been applied to those
      individuals, from the local bone marrow registry, with only one detectable HLA-B
      antigen by serology. The PCR-SSOP method detected the serologically defined HLA-B
      antigen in all cases. In addition, PCR-SSOP detected the presence of a second HLA
      B allele in 19.9% of these individuals. The method was also applied to all
      individuals where serology could only determine the HLA-B antigen as a broad
      specificity. All antigens were split by the PCR-SSOP method, indicating that the
      method is more specific than serology. Using a combination of PCR-SSOP and
      serologically determined types for 5000 individuals on the local bone marrow
      registry, HLA-B frequencies for the Northern Ireland population have been
      calculated.

PMID- 9028547
TI  - rhGM-CSF vs placebo following rhGM-CSF-mobilized PBPC transplantation: a phase
      III double-blind randomized trial.
AB  - In this placebo-controlled randomized trial we evaluated the hematological and
      clinical effects of r-Hu GM-CSF after high-dose chemotherapy (HDC) followed by GM
      CSF-mobilized PBPC transplantation. Fifty patients with poor prognosis
      malignancies were randomized in a double-blind study to receive either GM-CSF or
      placebo after HDC followed by PBPC rescue. For all patients, PBPCs were recruited
      using a combination of VP-16 (300 mg/m2 on days 1 and 2), cytoxan (3 g/m2 on days
      3 and 4) and GM-CSF (5 micrograms/kg from day 5). No differences were
      demonstrated between the two groups in median time to neutrophil or platelet
      recoveries. There was no significant difference between the GM-CSF group and the
      placebo group in the median duration of post-transplant hospitalization, in the
      number of days of antibiotic treatment, in the number of infections and in red
      blood cell or platelet transfusion requirements. There was a significant
      difference with an advantage for the placebo group in the mean duration of
      febrile days (P = 0.01). We conclude that the administration of GM-CSF in
      patients transplanted with GM-CSF-mobilized PBPC is not associated with a
      clinical benefit in term of tempo of engraftment, numbers of documented
      infections, transfusion requirements and mucositis grading.

PMID- 9028548
TI  - G-CSF post-autologous progenitor cell transplantation: a randomized study of 5,
      10, and 16 micrograms/kg/day.
AB  - G-CSF is routinely administered after autologous bone marrow or peripheral blood
      progenitor cell transplantation to enhance neutrophil engraftment. However, many
      different doses of G-CSF have been described with no clear consensus on the most
      cost-effective dose. We performed a prospective randomized trial examining the
      efficacy of three different doses of G-CSF post-autologous transplant (5, 10, or
      16 micrograms/kg/day). Fifty-seven consecutive patients with breast cancer (n =
      30), non-Hodgkin's lymphoma (n = 16), Hodgkin's disease (n = 6), multiple myeloma
      (n = 2), acute leukemia (n = 2), and testicular cancer (n = 1) were randomized,
      with 19 patients enrolled in each of the three treatment groups. All patients
      underwent a high-dose chemotherapy preparative regimen and received an autologous
      peripheral blood progenitor cell (PBPC) transplant (without bone marrow), with G
      CSF beginning on day 0. There was no difference in time to neutrophil engraftment
      among the three treatment groups (mean 10.2 to 10.8 days). There is a trend
      towards earlier platelet engraftment in the patient group receiving 5
      microgram/kg/day of G-CSF. The total cost of G-CSF by dose group was $2900,
      $4400, and $6500 per patient. We conclude that there was no advantage to the use
      of higher doses of G-CSF after autologous transplantation, and that lower doses
      are associated with lower costs.

PMID- 9028549
TI  - The treatment of relapsed or refractory intermediate grade non-Hodgkin's lymphoma
      with autologous bone marrow transplantation followed by cyclosporine and
      interferon.
AB  - In an effort to decrease the relapse rate following autologous bone marrow
      transplantation for non-Hodgkin's lymphoma, patients were given cyclosporine and
      interferon following autologous marrow transplantation. Forty patients with
      intermediate grade non-Hodgkin's lymphoma that was relapsed or refractory to
      standard chemotherapy underwent autologous marrow transplantation. The
      preparative regimen consisted of cyclophosphamide 6.8 g/m2, etoposide 1600 mg/m2,
      and carmustine 400 mg/m2 over 4 days followed by reinfusion of bone marrow.
      Intravenous cyclosporine was started on day -1 as a 16 mg/kg loading dose
      followed by 3.6 mg/kg/day for 28 days after transplant. Patients were begun on
      alpha-interferon (starting dose, 0.5 million units s.c. every other day)
      following platelet engraftment (median day 24 post-transplant) and continued on
      1.5 million units s.c. daily for 2 years. Regimen-related toxicities resulted in
      four (10%) deaths. Twenty-one (53%) patients developed marked erythema of the
      palms, soles, and arms. Biopsies of the erythema were consistent with grade I
      GVHD. Patients who did not develop rashes were not biopsied. The erythema
      persisted for a median of 10 days and resolved in all cases without treatment.
      Visceral GVHD was not apparent. All patients have been followed for a median of
      24 months (range 12-54 months). To date, only five patients (13%) have relapsed
      after bone marrow transplant. Multivariant analysis could not identify risk
      factors for relapse post-transplant. Disease-free survival of all patients is 77%
      (95% confidence interval, 67-93%). The results of this pilot study suggest that
      the administration of cyclosporine and interferon may decrease the relapse rate
      of relapsed/refractory non-Hodgkin's lymphoma following autologous bone marrow
      transplantation.

PMID- 9028550
TI  - Do patients with metastatic and recurrent rhabdomyosarcoma benefit from high-dose
      therapy with hematopoietic rescue? Report of the German/Austrian Pediatric Bone
      Marrow Transplantation Group.
AB  - Patients with primary metastatic or recurrent rhabdomyosarcoma (RMS) have a very
      poor prognosis. Since high-dose chemotherapy (HDC) +/- TBI was thought to improve
      survival, many centers performed this therapy using different types of
      hematopoietic rescue (auto BM or PBSC, allo BM). This is a retrospective, multi
      center analysis of the results of treatment in 36 patients with primary
      metastatic or relapsed RMS who were given HDC +/- TBI and hematopoietic rescue
      between 1986 and 1994. The median age was 6 years (< 1-22 years). Primary therapy
      was given according to either one of the Cooperative German Soft Tissue Sarcoma
      Studies CWS-81, -86, -91 or the European Study for Stage IV Malignant Mesenchymal
      Tumors in Childhood. There were 22 alveolar RMS, 13 embryonal RMS and one
      undifferentiated sarcoma. The indication for HDC was primary metastatic disease
      (27 patients) or a relapse of a primary localized tumor (nine patients). Thirty
      two patients were in 1st or 2nd CR when given HDC and four in VGPR. The median
      time from last event to HDC was 44 weeks (21-110). HDC consisted of fractionated
      melphalan ((4 x 30-45 mg/m2), VP16 40-60 mg/kg, carboplatin 3 x 400-500 mg/m2) in
      26 patients, 10 of whom received additional FTBI. Seven patients were treated
      with melphalan alone or in combination with carboplatin. Two patients received
      cyclophosphamide/busulphan with TLI (total lymphoid irradiation) and one
      cyclophosphamide with FTBI. Thirty-one patients were given autologous BM or PBSC
      as hematopoietic rescue and five allogeneic bone marrow from HLA-identical
      siblings. Fourteen patients received GM-CSF or G-CSF after hematopoietic stem
      cell transfusion (HSCT). Ten patients received adjuvant IL-2. There was one toxic
      HDC-related death. Nine patients are alive and free of disease with a median
      observation time of 57 months (32-108). The median time from HDC to relapse was 4
      months (1-17). The tumor recurred in the majority of patients at previously known
      sites; in three cases new metastatic sites were observed. Patients with primary
      localized tumors who had been treated with HDC because of relapse did slightly
      better (four of nine alive with NED) than patients with primary metastatic
      disease (five of 27 alive with NED). HDC is still of uncertain value in the
      therapy of poor-risk rhabdomyosarcoma and should be performed only as part of
      controlled clinical trials.

PMID- 9028551
TI  - No prevention of cytomegalovirus infection by anti-cytomegalovirus hyperimmune
      globulin in seronegative bone marrow transplant recipients. The Nordic BMT Group.
AB  - A randomized multicentre study was conducted to evaluate the effect of anti-CMV
      hyperimmune globulin in the prophylaxis of CMV infections in CMV seronegative
      allogeneic BMT patients who received a transplant from a seropositive donor or
      who had received blood products unscreened for CMV during the treatment before
      BMT. Twenty-eight patients were included in the study. Thirteen were randomized
      to receive and 15 not to receive intravenous CMV hyperimmune globulin. A dose of
      0.4 g/kg of immunoglobulin was given on day -8 and 0.2 g/kg on days -1, +7, +14,
      +21, +28, +35, +42, +56 and +70 in relation to the day of transplantation. Among
      the 15 patients not given immunoglobulin CMV was isolated in three, and two of
      them developed clinical CMV disease. In addition, one more patient developed CMV
      antibodies without virus isolation. In five of the 13 patients given
      immunoglobulin the virus could be isolated, and four of them developed CMV
      disease. One additional patient showed seroconversion but no other findings of
      CMV infection. The incidence of acute and chronic GVHD was similar in the two
      arms. There was no significant difference in survival. In conclusion, the present
      results do not indicate a beneficial effect of CMV hyperimmune globulin infusions
      in the prophylaxis of CMV infection or disease in seronegative allogeneic bone
      marrow transplant recipients from a seropositive donor.

PMID- 9028552
TI  - Hepatitis C virus genotypes and liver disease in patients undergoing allogeneic
      bone marrow transplantation.
AB  - Hepatitis C virus (HCV) genotypes were investigated in 57 HCV-infected patients
      undergoing allogeneic BMT at four European BMT units where death resulting from
      liver failure (LF) in HCV-infected patients varied from < 1% to > 80%. The aim of
      the study was to determine whether differing HCV genotypes could account for the
      different severity of post-transplant liver disease (LD). Sera from patients with
      pre (n = 22) or post-BMT (n = 35) HCV infection were collected from Italy
      (Genova, Monza), Sweden (Huddinge) and Germany (Ulm). Patients were grouped as
      follows: LF: 19/57; acute hepatitis (AH): 10/57 or chronic hepatitis (CH): 22/57;
      no liver disease (LD): 6/57. HCV genotypes were identified by hybridisation of
      the 5'UTR amplified products with type-specific oligonucleotides probes according
      to Simmonds (Hepatology 1994; 19: 1321-1324). Genotype HCV 1 was identified in 34
      patients (60%), HCV 2 in 15 (26%), HCV 3 in three (5%), mixed infection in three
      (5%) and undefined in two (3.5%). In the LF group HCV 1 was identified in 10/19
      and other genotypes in 9/19. Median timing of LF was earlier in patients infected
      with HCV 1 compared to other genotypes (45 and 68 days, respectively), largely
      due to the cause of LF; death from veno-occlusive disease (VOD) and hepatitis
      occurred at 30 and 68 days post-BMT, respectively. Genotype 1 was also identified
      in cases with no LD. These data indicate that there was no evident correlation
      between HCV genotype and type or severity of post-transplant liver disease.

PMID- 9028553
TI  - Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease
      after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka
      Bone Marrow Transplantation Group.
AB  - Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using
      the CMV antigenemia assay in 72 patients who received allogeneic bone marrow
      transplantation (BMT), and their incidences were compared between related and
      unrelated donor transplant patients. The incidence of CMV infection after BMT was
      significantly higher in patients who received transplants from HLA-matched
      unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05). CMV
      associated disease developed in 73% of unrelated and in 14% of sibling donor
      transplant patients (P < 0.01). The peak levels of CMV antigenemia were
      significantly higher in unrelated donors than in sibling donor transplant
      patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01). The
      median number of CMV antigen-positive cells on first detection was also
      significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01).
      The detection of CMV antigen-positive cells preceded the development of CMV
      associated disease in 18% of unrelated donor transplant patients, suggesting a
      lower predictive value of CMV antigenemia for subsequent CMV-associated disease
      in unrelated donor BMT. Careful monitoring and further studies are needed for the
      early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

PMID- 9028554
TI  - Liver function abnormality following treatment with antithymocyte globulin for
      aplastic anaemia.
AB  - We have observed transient elevations of serum alanine transaminase (ALT) levels
      in patients with aplastic anaemia who have been treated with antithymocyte
      globulin (ATG). Out of 18 patient episodes analysed retrospectively over a 12
      month period, 15 experienced increases in ALT levels with values ranging from 1.2
      to 18.5 times the upper limit of normal. In 11 of 15 episodes this was transient
      with ALT values returning to normal by 30 days, but in two patients this
      persisted for 6 months, and in a further two, until death at 34 and 145 days from
      unrelated causes. There was no evidence of acute viral infection or reactivation
      and no other drug toxicity could be implicated. We conclude that this may
      represent either a non-specific binding effect of ATG to hepatocytes or infection
      with an unidentified agent.

PMID- 9028555
TI  - Growth after bone marrow transplantation in young children conditioned with
      chemotherapy alone.
AB  - Short stature is a potential side-effect of BMT, brought about by the
      conditioning protocol and/or the complications of BMT. This study evaluates the
      effects of conditioning by chemotherapy, and BMT complications on growth. Thirty
      children conditioned for BMT by chemotherapy alone (cyclophosphamide and
      busulfan) were classified according to the occurrence of serious or prolonged
      complications after BMT: group 1 (n = 12) had no complication, while group 2 (n =
      18) did. Fifteen of them were severely growth retarded (< or = -2 s.d.) at BMT,
      because of their initial disease. At the time of BMT, the two groups had similar
      ages (1.0 +/- 0.2, s.e.m. year, in group 1 and 1.7 +/- 0.5 year in group 2),
      height (-1.7 +/- 0.5; -1.8 +/- 0.3 s.d.) and plasma insulin-like growth factor I
      (IGFI) levels (0.3 +/- 0.1 U/ml in both). Group I grew significantly and their
      plasma IGFI increased but group 2 did not, as assessed 2 years post-BMT. We
      conclude that conditioning with chemotherapy alone does not prevent the catch-up
      growth induced by BMT in young children; the lack of catch-up growth is due to
      complications occurring after BMT, and the change in plasma IGFI suggests that
      complications of BMT prevent any increase in plasma IGFI, and thereby catch-up
      growth.

PMID- 9028556
TI  - Quality of life following bone marrow transplantation for breast cancer: a
      comparative study.
AB  - As more women are treated with bone marrow transplantation (BMT) for breast
      cancer, there is growing interest in quality of life (QOL) following treatment.
      Although there have been some clinical studies of QOL following BMT, this area
      has received little systematic attention. In particular, it is unclear how QOL
      for women treated with BMT for breast cancer differs from that which might be
      expected for 'healthy' women of about the same age. To address this issue, we
      compared QOL reported by women treated with autologous BMT for breast cancer with
      that of a group of women of similar age with no history of cancer. In addition,
      we examined the relationship of demographic factors, medical factors, and self
      reported symptom prevalence, severity, and distress to QOL in post-BMT patients.
      All participants completed the SF-36 Health Survey developed from the Medical
      Outcomes Study (SF-36). Post-BMT patients also completed the ECOG Performance
      Status Rating Scale (PSR) and the Memorial Symptom Assessment Scale (MSAS).
      Results indicated that, compared to the women with no cancer history, post-BMT
      patients reported significantly impaired physical functioning, physical role
      functioning, general health, vitality, social functioning, and emotional role
      functioning. Impaired QOL following BMT was significantly associated with lower
      income, a longer time to engraftment, longer hospital stay, poor performance
      status, and greater symptom prevalence, severity, and distress. The problems
      identified in this study may be important targets for intervention when trying to
      improve QOL following BMT.

PMID- 9028557
TI  - Effect of the in vivo priming regimen for peripheral blood stem cells (PBSC)
      mobilization on in vitro generation of cytotoxic effectors by IL-2 activation of
      PBSC in a murine model.
AB  - Priming of patients with different PBSC mobilizing regimens leads to an increase
      by several fold in circulating hematopoietic progenitors in peripheral blood.
      However, the effect of these mobilizing regimens on lymphoid cells contained
      within the harvested PBSC population is not well understood. We have studied the
      effect of CY and/or G-CSF +/- IL-2 containing regimens on lymphoid cells, and
      their capacity to give rise to cytotoxic effectors on subsequent in vitro IL-2
      activation in a murine model of PBSC mobilization. C57B1/6 mice were given CY 100
      or 200 mg/kg on day 0 followed 48 h later by G-CSF 125 micrograms/kg twice a day
      and/or IL-2 60000 i.u. twice a day in different schedules. Mice were sacrificed
      on day 4, 6, 8 and 10 following CY and the number of hematopoietic progenitors
      mobilized to the spleens of these mice was assessed by CFC assay and cytotoxicity
      was evaluated by 4 h 51Cr release assay against both NK-sensitive (Yak-1), and NK
      resistant (B16, C1498) cell lines after 24 h in vitro IL-2 activation in the
      presence of 6000 i.u./ml of IL-2. Peak numbers of CFC in the splenic PBSC
      population were seen on day 6 following CY. Administration of CY 200 mg/kg +
      GCSF, the most potent regimen for CFC mobilization, led to a marked decrease in
      proportion of CD3+ cells in day 6 PBSC as compared to controls (17.7% vs 3.9%)
      and was associated with a significant decrease in generation of cytotoxic cells
      after IL-2 activation. Combining IL-2 to CY + G-CSF prevented the marked loss in
      cytotoxicity associated with this regimen without any decrease in number of CFC
      mobilized. When IL-2 was combined with CY without G-CSF, the number of CFC
      mobilized was comparable to that seen with CY + G-CSF and these CY + IL-2
      mobilized PBSC generated potent cytotoxic effectors after in vitro IL-2
      activation. Thus our results indicate that combining IL-2 with a PBSC mobilizing
      regimen can avert a decrease in the cytotoxic potential of mobilized cells
      without compromising the number of hematopoietic progenitors.

PMID- 9028558
TI  - Cost-effectiveness of autologous bone marrow transplantation in patients with
      relapsed non-Hodgkin's lymphoma.
AB  - The analysis of published survival curves can be used as the basis for conducting
      cost-effectiveness analyses in which two treatments are compared in terms of cost
      per life year saved. In patients with relapsed chemosensitive non-Hodgkin's
      lymphoma, autologous bone marrow transplantation (ABMT) has been reported to
      improve survival in comparison with control patients who receive standard
      chemotherapy. An incremental cost-effectiveness analysis was undertaken in which
      the Gompertz model was used to determine a lifetime estimate of patient-years
      gained by subjects given ABMT in comparison with controls. Our study utilised the
      cost data calculated by Uyl-de Groot et al and the clinical data reported by
      Philip et al. This latter randomised clinical trial involved 55 patients
      subjected to ABMT and 54 controls given chemotherapy. Lifetime survival advantage
      for patients of the ABMT group was estimated as 3606 discounted patient-months
      every 100 patients. The use of ABMT as opposed to standard chemotherapy was found
      to imply an incremental cost of $9,229 per discounted life year gained (95% CI of
      $5,390 to $24,012). The cost-effectiveness ratio of ABMT in patients with
      relapsed chemosensitive non-Hodgkin's lymphoma is noticeably favourable.

PMID- 9028560
TI  - Hyperkalemia associated with cyclosporine (CsA) use in bone marrow
      transplantation.
AB  - Two adult leukemia patients underwent allogeneic bone marrow transplantation and
      received cyclosporine (CsA) as part of their immunosuppressive therapy. Despite
      adequate kidney function, both patients developed hyperkalemia. Cyclosporine was
      the only pharmaceutical agent to which this electrolyte abnormality could be
      attributed. Although the mechanism of the hyperkalemia is unclear, it seems to be
      related to an aldosterone-resistant state. Cyclosporine-induced hyperkalemia is a
      relatively common occurrence; however, there is only a single 'case report'
      addressing this phenomenon in bone marrow transplantation patients. We propose
      both mechanisms and methods of managing CsA-associated hyperkalemia in allogeneic
      transplantation patients.

PMID- 9028559
TI  - The effects of a simplified method for cryopreservation and thawing procedures on
      peripheral blood stem cells.
AB  - A simplified method for cryopreservation at -80 degrees C of peripheral blood
      stem cells (PBSC) has been increasingly used for autologous PBSC transplantation
      in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5%
      dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing,
      has several advantages over the conventional method using 10% DMSO with rate
      controlled freezing, little is known about effects of long-term cryopreservation
      for years and thawing process on hematopoietic progenitors. We examined the
      recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the
      simplified method under various conditions as follows: (1) long-term storage for
      1-5 years; (2) DMSO exposure for 1 h after rapid thawing; and (3) thawing at a
      lower temperature other than 37 degrees C. In our study, we found that the
      recovery rates of BFU-E and CFU-GM were not affected by the length of
      cryopreservation period; they remained at more than 70% on average for 16-61
      months. In our hands, a 1-h exposure to DMSO after rapid thawing was not toxic
      for hematopoietic progenitors. Furthermore, there was no significant difference
      in the recovery rates of BFU-E and CFU-GM between thawing at 37 degrees C and 20
      degrees C. These observations indicate that PBSC cryopreserved for at least 5
      years by the simplified method can be used clinically without losing
      hematopoietic activity, and suggest that hematopoietic activity of the thawed
      PBSC may be unaffected when PBSC are infused slowly within 60 min or even when
      PBSC are thawed gradually at room temperature.

PMID- 9028561
TI  - Esophageal aspergillosis after bone marrow transplant.
AB  - The prolonged immune suppression associated with bone marrow transplants
      predisposes to fungal infections including Aspergillus. Disseminated
      aspergillosis occurs in up to 60% of patients with invasive pulmonary
      aspergillosis; sites of involvement include the brain, gastrointestinal tract,
      kidney, liver, thyroid, heart, and spleen. There is only one report of isolated
      esophageal aspergillosis. A recent acute myelogenous leukemia patient had
      isolated esophageal aspergillosis after bone marrow transplantation which was
      successfully treated with amphotericin B.

PMID- 9028562
TI  - Rapid engraftment after allogeneic ABO-incompatible peripheral blood progenitor
      cell transplantation complicated by severe hemolysis.
AB  - A patient with CML in accelerated phase received G-CSF-mobilized PBPC from an
      unrelated HLA genotypically matched donor. The blood groups of the patient and
      donor were bidirectionally incompatible. Hematologic recovery was rapid with >
      500 PMN/microliter on day +9. Starting on day +5 bilirubin levels increased from
      1.3 mg/dl up to a maximum of 18 mg/dl on day +14. Clinical signs and laboratory
      tests supported major hemolysis. Blood typing on day +16 revealed early blood
      group change, consistent with donor-derived antibodies produced by passenger
      lymphocytes which may have mediated severe hemolysis. The early onset and strong
      intensity of the hyperbilirubinemia could be a specific feature of ABO
      incompatible allogeneic PBPC transplantation which would be difficult to
      differentiate from GVHD or VOD.

PMID- 9028563
TI  - Unrelated peripheral blood stem cell transplantation for Fanconi anemia.
AB  - The Brazilian unrelated bone marrow donor program began in 1993 and an unrelated
      matched donor was found for a Fanconi anemia patient without a sibling match. An
      11-year-old female recipient received FTBI (6.0 Gy) and cyclophosphamide (40
      mg/kg) as conditioning. The 41-year-old female unrelated donor received G-CSF at
      5 micrograms/kg x 5 days, and on day 6 and 7 postmobilization, peripheral blood
      stem cells were harvested. Engraftment was seen on day 19 post-BMT and she
      remains alive and well on day 191+. This case supports the potential role of
      harvesting G-CSF-stimulated PBSC for unrelated bone marrow transplantation.

PMID- 9028564
TI  - Cokeromyces recurvatus infection in a bone marrow transplant recipient.
AB  - Diarrhea is common after bone marrow transplants. We report Cokeromyces
      recurvatus infection in a transplant recipient with diarrhea. Treatment with
      mystatin was effective.

PMID- 9028565
TI  - On the origin of a species: evolution of health sciences librarianship.
AB  - The basic role of the health sciences librarian has not significantly changed
      throughout history. It has been- and remains-to collect information and organize
      it for effective use. What has changed is the environment in which this role is
      carried out and the tools used to accomplish the tasks. Over the one hundred-year
      history of the evolution of health sciences librarianship, we have used specialty
      education as the mechanism for differentiating ourselves from other types of
      librarianship and for acquiring the knowledge and skills to succeed in our
      profession. Changing conditions require a continual review of our specialty
      education and a willingness to modify it in order to prepare ourselves for
      changing environments. A review of specialty education for health sciences
      librarianship reveals that we have always adapted to new and changing conditions
      and will continue to do so in the future.

PMID- 9028566
TI  - Primary clientele as a predictor of interlibrary borrowing: a study of academic
      health sciences libraries.
AB  - Statistics obtained from the Association of Academic Health Sciences Library
      Directors (AAHSLD) member libraries were studied during 1991/92 to determine
      whether the size of the primary client pool is a better predictor of a library's
      interlibrary loan (ILL) borrowing than is collection size. In libraries with
      collections of fewer than 70,000 serial and monograph titles, size of the client
      base explained 25% of the variation in ILL borrowing. No measure of collection
      size helped explain a greater percentage of the variability. This relationship
      was not found in libraries with collections of more than 70,000 titles. Further
      research into the predictors of ILL borrowing volume in the relatively controlled
      environment of the OhioLINK system is proposed.

PMID- 9028567
TI  - The impact of consumer health information provided by libraries: the Delaware
      experience.
AB  - In the past two decades, consumer health libraries have proliferated in response
      to the changing health care environment and consumer demand. While this growth of
      consumer health resources and services has been extensively described in the
      literature, there is little documentation about the impact and value of providing
      consumer health information. This paper explores the issues of impact and value
      as examined in a retrospective study of consumers who received health information
      from the Delaware Academy of Medicine's Consumer Health Library during 1995. In
      this study, 270 adults were mailed a questionnaire that focused on whether the
      information influenced decisions, actions, anxiety levels, and patient-provider
      communication. The questionnaire also addressed the value of such library service
      in terms of likelihood of repeat use, recommendation to others, and willingness
      to pay. The results, based on a return rate of 86.7%, identified effects of
      library-supplied consumer health information that extend beyond the anticipated
      acquisition of knowledge to specific actions and effects on anxiety. The value of
      consumer health library information service was shown by the extremely high
      percentage of probable repeat use and recommendation to others, the willingness
      of 83.8% of the respondents to pay for such service, and the copious comments
      volunteered by the respondents.

PMID- 9028568
TI  - Communication on a listserv for health information professionals: uses and users
      of MEDLIB-L.
AB  - BACKGROUND: Listservs offer the potential for participants to engage in a
      "virtual conference" with experts and colleagues from around the world. However,
      little research has been done to study the use and effectiveness of this means of
      communication. METHODS: In April 1995, an electronic survey of MEDLIB-L
      subscribers was conducted to determine demographic characteristics and uses of
      the listserv. RESULTS: Respondents worked predominately at academic institutions
      (45%) as members of large staffs (44%) in the United States (82%). The majority
      had worked as health information professionals for more than ten years. Nearly
      90% of respondents read MEDLIB-L at work and most spent fewer than three hours
      per week doing this. More than half of the respondents read 41% to 100% of the
      messages distributed by the list, with fewer than 20% reading 91% to 100% of the
      messages. Respondents reported initiating and responding to reference questions
      and product information with greatest frequency. There was no relationship
      between years of experience in the profession and participation in listserv
      activities except in the category of posting information. CONCLUSIONS: This study
      describes communication activities on MEDLIB-L and the extent of subscriber
      participation in these activities.

PMID- 9028569
TI  - Assessing research productivity in an oncology research institute: the role of
      the documentation center.
AB  - An evaluation method used to assess the quality of research productivity and to
      provide priorities for budget allocation purposes is presented. This method,
      developed by a working group of the National Institute for Research on Cancer
      (IST), Genoa, Italy, is based on the partitioning of categories of the Science
      Citation Index and Journal Citation Reports (SCI-JCR) into deciles, which
      normalizes journal impact factors in order to gauge the quality of the
      productivity. A second parameter related to the number of staff of each institute
      department co-authoring a given paper has been introduced in order to guide
      departmental budget allocations. The information scientists of the IST
      Documentation Center who participated in the working group played a pivotal role
      in developing the computerized database of publications, providing and analyzing
      data, supplying and evaluating literature on the topic, and placing international
      bibliographic databases at the working group's disposal.

PMID- 9028570
TI  - Equalizing rural health professionals' information access: lessons from a follow
      up outreach project.
AB  - A follow-up outreach project was undertaken to extend and reinforce the work of a
      National Library of Medicine-funded outreach project conducted in west central
      Illinois in 1991. The participants included five of the eight original sites as
      well as additional populations. An evolving partnership with the state's Center
      for Rural Health expanded the project's geographic area statewide. Evaluation
      showed benefits of varied training formats, reexposure to end-user searching, and
      the importance of "readiness." Follow-up training and longer trials for practice
      searching resulted in greater volume of search and document delivery activity.
      Varied training formats proved successful in reaching specific groups. Loansome
      Doc activity throughout the eighteen-month project suggested sustained use of
      Grateful Med beyond the two-month trial periods. The introduction of Grateful
      Med/Loansome Doc to unaffiliated health professionals is an important component
      in equalizing information access. Future information service initiatives are
      suggested to meet the challenge of building a rural information infrastructure
      and support system for health professionals.

PMID- 9028571
TI  - Providing library services to a remote non-traditional program for health career
      students: the Kellogg experience.

PMID- 9028572
TI  - First-year medical students' information needs and resource selection: responses
      to a clinical scenario.

PMID- 9028573
TI  - The effect of hospital proximity and numbers of students on reference service in
      medical school libraries.

PMID- 9028574
TI  - SPIRS, WinSPIRS, and OVID: a question of free-text versus thesaurus retrieval?

PMID- 9028575
TI  - Precocious dinosaur or preeminent electronic presence?

PMID- 9028576
TI  - Depressed smooth muscle contractility after massive intestinal resection in rat:
      role of alterations in muscarinic receptor status or source of calcium for
      excitation-contraction coupling.
AB  - Following massive intestinal resection (removal of 75% of the mid-jejunoileum) in
      the rat, there is a significant reduction in the in vitro tonic contractile
      response of the remaining jejunal circular smooth muscle in response to
      stimulation with the muscarinic agonist bethanechol. The aim of these experiments
      was to determine if this alteration is specific to muscarinic excitation and
      occurs as a result of changes in the source and availability of calcium required
      for excitation-contraction coupling, or reflects changes in muscarinic receptor
      number and (or) affinity. The contractile response of proximal jejunal circular
      muscle strips from sham-operated and resected rats was studied in vitro in
      response to electrical field stimulation, serotonin, and bethanechol, the later
      under conditions where extracellular calcium was absent or entry was excluded. In
      contrast with the significant reduction in tonic contractile response to
      muscarinic excitation of tissues from resected animals, there was an equivalent
      or enhanced response of these tissues to electrical field stimulation and
      serotonin, respectively. While sham-operated and resected groups showed similar
      dependency upon or availability of intracellular and extracellular calcium, the
      data indicate distinct pathways of calcium mobilization for tonic versus phasic
      contractile activity. Muscarinic receptor number and affinity were assessed by 1
      quinuclidinyl[pheny1-4-3H]benzilate ([3H]QNB) binding to isolated smooth muscle
      cells and showed a significant increase in Bmax, with no change in Kd after
      resection. Thus, the reduced contractility of the circular muscle of the remnant
      jejunum after massive intestinal resection is a specific even associated with
      muscarinic receptor activation, but it is not the result of either an alteration
      in the source or availability of calcium required for excitation-contraction
      coupling or a reduction in the number and (or) affinity of muscarinic receptors.

PMID- 9028577
TI  - In vitro study of the effect of miglitol on carbohydrate digestion and intestinal
      metabolism in normal and non-insulin-dependent diabetic rats.
AB  - The effect of miglitol was studied (20 mg/kg body weight), administered
      intraduodenally alone or together with maltose, on the absorption and intestinal
      metabolism of glucose during its translocation from the lumen of the intestine to
      the blood, using in vitro perfused preparations of complete small intestine
      pancreas, proximal small intestine alone, or distal small intestine alone,
      isolated from normal and non-insulin-dependent diabetic rats. In the absence of a
      luminal administration of maltose in normal rats, the glucose uptake from the
      vascular perfusate was greater in the presence (0.52 +/- 0.04 mmol/h) than in the
      absence (0.39 +/- 0.02 mmol/h) of miglitol (p < 0.05). In diabetic rats, no
      significant variations were observed in glucose uptake from the vascular
      perfusate as an effect of miglitol, but the glucose uptake in the presence of
      this drug was significantly less (p < 0.05) than that observed in normal rats.
      Portal lactate was significantly greater (p < 0.05) in diabetic than in normal
      rats and, after administration of miglitol, rose in both normal and diabetic
      rats, the rise being significantly greater in normal than in diabetic rats (p <
      0.01). When maltose was administered luminally (2 g/kg body weight), the values
      of portal glucose in both normal and diabetic rats were significantly less in the
      presence of miglitol in the complete as well as in the distal and proximal small
      intestine preparations (p < 0.05); the glucose uptake from luminal administered
      maltose was greater in the presence of miglitol in diabetic (p < 0.05) and in
      normal (p < 0.05) rats except in the complete small intestine of normal rats; and
      no significant differences were observed in portal lactate levels between normal
      and diabetic rats in the presence of miglitol. In conclusion, our results show
      that miglitol administered luminally at the doses employed here, as well as
      reducing the transport of glucose from the lumen of the intestine into the blood
      supply, significantly stimulate intestinal glucose metabolism.

PMID- 9028578
TI  - Endothelial binding sites for lipoprotein lipase are not diminished in perfused
      hearts from diabetic rats.
AB  - The possibility that diabetes reduces functional, heparin-releasable lipoprotein
      lipase (HR-LPL) activity on the coronary vasculature of perfused hearts by
      altering endothelial binding sites for the enzyme was examined by measuring the
      binding and subsequent heparin-induced release of exogenous lipoprotein lipase
      purified from bovine milk (mLPL). Rat hearts were first perfused with heparin (5
      U/mL) for 5 min to displace endogenous HR-LPL into the perfusate. The subsequent
      perfusion of control hearts with 0.05-2 micrograms/mL mLPL resulted in a
      progressive increase in bound exogenous enzyme that could be released by a second
      heparin perfusion. Induction of an acute, insulin-deficient model of diabetes
      (100 mg/kg streptozotocin 4-5 days prior to heart perfusions) reduced endogenous
      HR-LPL activity, but the binding and heparin-induced release of mLPL (0.5
      microgram/mL) were the same as measured in control hearts. Therefore, diabetes
      does not alter low-affinity, high-capacity proteoglycan binding sites for mLPL on
      the endothelium of perfused hearts.

PMID- 9028579
TI  - Effect of endogenous L-arginine on the measurement of nitric oxide synthase
      activity in the rat kidney.
AB  - The endogenous level of L-arginine in renal cortex, outer medulla, and inner
      medulla and its effect on the measurement of nitric oxide synthase (NOS) activity
      in these regions was determined. L-Arginine was measured with an amino acid
      analyzer and total NOS activity was measured as the rate of formation of
      radiolabeled L-citrulline from L-[14C]arginine. Total NOS activity was that
      activity inhibited by NG-nitromonomethyl-L-arginine (300 microM). The endogenous
      L-arginine concentration was 452 +/- 45 (mean +/- SEM), 313 +/- 25, and 95 +/- 8
      pmol/mg wet weight in the cortex, outer medulla, and inner medulla, respectively
      (n = 12). Total NOS activity was 61 +/- 19, 709 +/- 94, and 1347 +/- 76 pmol.h
      1.mg protein-1 in the cortex, outer medulla, and inner medulla, respectively,
      when endogenous L-arginine was not considered in the calculation. Correcting for
      endogenous L-arginine gave values of 185 +/- 61, 1714 +/- 239, and 1707 +/- 104
      pmol.h-1.mg protein-1, respectively. Dowex extraction to remove endogenous L
      arginine from samples also increased NOS activity in cortex and medulla. The data
      indicate that there is a differential distribution of endogenous L-arginine in
      the kidney and that these levels must be taken into account when measuring NOS
      activity. NOS activity is also distributed differentially, with activity in the
      medulla being nearly 10-fold higher than in the cortex.

PMID- 9028580
TI  - Susceptibility of spontaneously hypertensive rats to the diabetogenic effects of
      streptozotocin.
AB  - Several studies have utilized the spontaneously hypertensive (SHR) diabetic rat
      to document the synergistic deleterious consequences of diabetes and hypertension
      on various organ systems. However, whether these effects are due entirely to the
      overlapping pathological states or partially result from a greater susceptibility
      of SHR rats to the diabetogenic effects of streptozotocin (STZ) is unclear. The
      present study was conducted to examine if strain-dependent variabilities in the
      STZ-induced diabetic state could also contribute to the pronounced complications
      previously observed in the SHR diabetic rat. To eliminate a possible modulating
      influence of severe hypertension on the beta-cytotoxic efficacy of STZ, SHR
      (SHRD), and Wistar (WisD) rats were injected with STZ (55 mg/kg i.v.) at 7-8
      weeks of age, a time when there was no significant difference in systolic blood
      pressure between both stains. An oral glucose tolerance test was performed at 1
      week following STZ and animals were killed at 2 weeks. Although both diabetic
      groups were equally hyperglycemic in the fed state, only SHRD rats had
      significantly elevated fasted glycemia at 1 week. Plasma insulin levels in the
      fed state or in response to oral glucose, as well as pancreatic insulin contents
      were diminished to a greater extent in the SHRD group relative to WisD. Fed
      plasma triglyceride (TG) levels were elevated only in the SHRD group, in
      association with a 4-fold reduction in basal circulating lipoprotein lipase (LPL)
      activity. However plasma TG clearance and LPL activity in response to i.v.
      heparin were not significantly altered in SHRD relative to SHR controls. The
      results in this study indicate that when evaluating the combined effects of
      diabetes and spontaneous hypertension, the STZ dose should be titrated to obtain
      an identical degree of diabetes in the SHR and a normotensive strain. In this
      regard, 45 (SHR) and 55 (Wistar) mg/kg STZ produced an identical milieu of
      diabetes.

PMID- 9028581
TI  - Abnormal regulation of cytosolic calcium and pH in platelets of Sabra rats in
      early phases of salt hypertension development.
AB  - Platelet cytosolic free calcium concentration ([Ca2+]i) and pH (pHi) have been
      reported to be altered in both human essential and rat spontaneous hypertension.
      The aim of our study was not only to search for the occurrence of such
      alterations in platelets of rats with salt-induced hypertension but also to
      investigate whether these changes might precede blood pressure rise in this form
      of experimental hypertension. Using fluorescent probes fura-2 and BCECF, basal
      values and thrombin-induced changes of [Ca2+]i and pHi were determined in
      platelets of young hypertension-prone (SBH) and hypertension-resistant (SBN)
      Sabra rats fed either low-salt (0.3% NaCl) or high-salt (4% NaCl) diets. Under
      the conditions of low salt intake, basal [Ca2+]i values were similar in SBH and
      SBN rats, whereas pHi was significantly lower in SBH than in SBN animals.
      Thrombin induced smaller [Ca2+]i elevation but greater pHi rise in SBH rats
      compared with SBN animals. The initial rate of thrombin-induced Mn2+ entry, which
      reflects the opening of a particular subclass of thrombin-operated Ca2+ channels,
      was similar in both strains. The moderate hypertension elicited in SBH rats by
      high salt intake was not associated with major alterations of basal [Ca2+]i or
      pHi values. High salt diet feeding did not influence [Ca2+]i and pHi responses to
      thrombin in either strain. In contrast, high salt intake reduced thrombin-induced
      Mn2+ entry in SBN but not in SBH rats. Basal platelet [Ca2+]i values correlated
      positively with systolic but not with diastolic blood pressure. This could be
      ascribed to a very close relationship of basal [Ca2+]i values with pulse
      pressure. The abnormalities of [Ca2+]i and pHi handling in platelets of Sabra
      rats with salt-dependent genetic hypertension differ from those described in
      essential hypertensive patients or rat strains with spontaneous forms of genetic
      hypertension. Our study also indicated that alterations of platelet [Ca2+]i do
      not precede blood pressure elevation in salt hypertension.

PMID- 9028582
TI  - A physical-chemical analysis of the acid-base response to chronic obstructive
      pulmonary disease.
AB  - The metabolic contributions to chronic acid-base changes were examined in the
      plasma of arterial blood in patients with chronic obstructive pulmonary disease
      (COPD) and chronic hypercapnia, by a quantitative physical-chemical analysis.
      Patients were stratified into three groups: group 1 (Paco2 less than 40 mmHg; 1
      mmHg = 133.3 Pa), group 2 (Paco2 between 40 and 50 mmHg), and group 3 (Paco2
      higher than 50 mmHg). With the development of hypercapnia (Paco2 from 38.2 +/-
      1.6 to 53.8 +/- 0.6 mmHg) and hypoxemia (Pao2 from 73.6 +/- 2.5 to 62.1 +/- 2.1
      mmHg), blood pH decreased slightly (from 7.405 +/- 0.007 to 7.372 +/- 0.009). The
      strong ion difference ([SID]) increased in the hypercapnic group (from 39.7 +/-
      1.7 to 46.2 +/- 2.9 mequiv.L-1) parallel to the increase in [HCO3-] (from 23.8 +/
      0.5 to 30.8 +/- 0.8 mequiv.L-1). The change in [SID] was quantitatively similar
      to the [HCO3-] change, thus reflecting a metabolic compensation of chronic
      respiratory acidosis. [SID] increase was mainly accounted for by changes in the
      [Na+]/[Cl-] ratio due to a significant decrease in plasma [Cl-]. Other ions
      measured as well as the weak acid buffers ([ATOT]) remained constant. From the
      present results, we suggest the usefulness of the physical chemical approach in
      the characterization of acid-base disturbances due to chronic hypercapnia when
      water retention or protein depletion are expected further to hypochloremia, as
      can be the case in severe COPD patients.

PMID- 9028584
TI  - Effects of nitric oxide synthase blockade on esophageal peristalsis and the lower
      esophageal sphincter in the cat.
AB  - The present study explores the role of nitric oxide (NO) in control of esophageal
      peristalsis and lower esophageal sphincter (LES) function in the cat. Studies
      were performed on 20 ketamine-anesthetized cats with manometric recording at the
      LES, 0, 2, 4, and 6 cm above the LES (smooth muscle section), and 12 and (or) 14
      cm above the LES (striated muscle section). L-Ng-Nitro-arginine (L-NNA, 10(-6)
      10(-4) mol/kg) was given intravenously, and the effects on swallow-induced
      esophageal peristalsis were assessed. (i) L-NNA increased the velocity of swallow
      induced peristalsis in the smooth muscle esophagus; the effect was dose
      dependent, more prominent distally, and completely reversed by L-arginine (10(-3)
      mol/kg). (ii) L-NNA decreased the amplitude of peristaltic contraction in the
      very distal esophagus; the decrease also was dose dependent but not returned to
      normal by L-arginine. (iii) L-NNA inhibited LES relaxation (reversed by L
      arginine) and decreased the LES "after-contraction" amplitude (unaffected by L
      arginine). (iv) L-NNA was associated with the appearance of repetitive
      contractions. Basal LES tone was unaffected by L-NNA. In conclusion, NO is an
      important mediator for the timing of peristalsis in the distal smooth muscle
      esophagus and for LES relaxation in the cat, a species whose contraction
      amplitude is largely determined by cholinergic excitation. The role of NO in
      controlling esophageal body and LES contraction amplitude, and in preventing
      repetitive contractions, requires further study.

PMID- 9028585
TI  - Ventilatory effects of angiotensin and vasopressin in conscious rats.
AB  - Angiotensin II (ANG II) stimulates ventilation (V), when ventilatory baroreceptor
      reflexes are taken into account, and arginine vasopressin (AVP) causes baroreflex
      inhibition of V in conscious and anesthetized dogs. To study mechanisms of
      hormonal modulation of V, a conscious rat model was investigated. V and
      metabolism were measured during steady-state intravenous infusions of ANG II and
      AVP in Sprague-Dawley rats (mean arterial pressure (MAP) increased 20 mmHg (1
      mmHg = 133.3 Pa)). These data were compared with observations during equal
      pressor infusions of phenylephrine (PE), an agent classically used to study
      baroreceptor reflexes. V, respiratory frequency (f), and tidal volume (Vt) were
      maintained during the increased MAP associated with ANG II infusions, a response
      identical with that reported in conscious dogs. However, unlike dogs, AVP
      infusion did not depress V and metabolism in rats. PE in conscious rats caused an
      unexpected increase in Vt and V in association with increased metabolism. None of
      the pressor agents affected breath timing when the latter was binned by breath f.
      Since there was no obvious baroreflex inhibition of V with AVP and PE, potential
      stimulatory effects of ANG II on respiration could not be discerned. As well, the
      ventilatory baroreceptor pressure threshold may be higher or adaptation of the
      reflex may be faster in conscious rats than in dogs.

PMID- 9028583
TI  - Canine bronchial sustained contraction in Ca2+-free medium: role of intracellular
      Ca2+.
AB  - We evaluated whether cartilage was a source of Ca2+ and the possible role of Ca2+
      recycling in the sustained bronchial contraction (SBC) induced by carbachol (Cch)
      in Ca2+-free medium. Canine first-order bronchi were studied with cartilage and
      epithelium (+CAR + EPI) and without these structures individually (-CAR + EPI and
      +CAR - EPI) or together (-CAR - EPI). After cartilage removal (-CAR - EPI or -CAR
      + EPI) Cch produced a transient contraction in Ca2+-free medium. Removal of the
      epithelium alone had minor effects on the magnitude of the SBC but increased the
      effect of removal of cartilage to diminish the SBC. Bronchial strips with
      cartilage were able to respond to Cch with lower Ca2+ concentrations (10-100
      microM) than could dissected preparations. Preincubation with BAY K 8644 (30-1000
      nM) or 60 mM KCl or -CAR - EPI tissues converted the transient contractions to
      Cch in Ca2+-free medium to sustained contractions. In microelectrode studies, 50
      nM Cch induced membrane oscillations in solutions with 2.5 mM Ca2+ in bronchial
      preparations, plus or minus cartilage, and in undissected tissues in Ca2+-free
      medium but not in -CAR - EPI tissues. Preincubation with 1 microM BAY K 8644 in
      Ca(2+)-free medium restored these oscillations in -CAR - EPI tissues. The release
      of 45Ca2+ from cartilage was too rapid to provide a reservoir of Ca2+ to support
      multiple SBCs in Ca2+-free medium. Moreover, in the Ca2+-free medium (with 10 nM
      Ca2+ after tissue +CAR + EPI incubation) excitatory junction potentials rapidly
      disappeared. Addition of 1 microM nifedipine or 1 mM EGTA during the SBC of +CAR
      + EPI tissues produced complete relaxation. A transient contraction to Cch
      occurred with prior addition of nifedipine. Inhibition of the sarcoplasmic
      reticulum Ca2+ pump by tissue incubation with cyclopiazonic acid (CPA; 10
      microM), or briefly with 1 mM EGTA significantly diminished the SBC induced by
      Cch in Ca2+-free medium. CPA and EGTA together abolished the Cch-induced SBC.
      Thus, cartilage plays a more complex role than as a Ca2+ reservoir to support the
      SBC induced by Cch in Ca2+-free solution; its removal affects the process
      supporting SBCs involving intracellular Ca2+ storage and Ca2+ entrance through
      voltage-dependent channels.

PMID- 9028586
TI  - Inhibition of nicotinic cholinoceptor mediated current in vagal motor neurons by
      local anesthetics.
AB  - The effects of local anesthetics on ligand-gated cation channel currents were
      examined in rat brainstem vagal motoneurons. Etidocaine (0.1-20 microM) blocked
      nicotinic cholinoceptor gated currents in cells voltage-clamped at -60 mV in a
      concentration-dependent manner, but at concentrations up to 100 microM did not
      inhibit glutamate receptor currents induced by (+/-)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA), N-methyl-D-aspartate (NMDA), or glutamate.
      Relative to etidocaine, procaine displayed about 10-fold lower potency in
      antagonizing acetylcholine and its inhibitory effect, unlike that of etidocaine,
      was rapidly reversed by washout. Ketamine (10 microM) caused a 2-fold larger
      decrease in NMDA current than acetylcholine current, but did not affect AMPA
      current. In conclusion, (i) etidocaine and procaine possess a moderately potent
      blocking activity at nicotinic cholinoceptor gated channels in brainstem vagal
      motoneurons and (ii) in contrast with ketamine, both agents showed similar
      selectivity in that neither inhibited glutamate receptor gated channels at
      concentrations up to 0.1 mM.

PMID- 9028587
TI  - Tissue blood flow distribution and the effect of chronic vascular catheterization
      in the hind limb of the fetal lamb.
AB  - In six chronically instrumented fetal lambs, hind-limb skin, bone, and muscle
      comprised 22.5 +/- 1.3, 35.3 +/- 1.6, and 42.3 +/- 1.1% of total limb weight,
      respectively. As estimated using radionuclide-labeled microspheres, blood flow to
      these tissues averaged 30.4 +/- 4.9, 30.1 +/- 3.3, and 14.0 +/- 3.1 mL.min-1.100
      g-1, respectively, and they received 29.5 +/- 3.3, 45.3 +/- 3.6, and 25.2 +/-
      4.5% of total limb blood flow. Thus, muscle has a lower blood flow in relation to
      its weight in comparison with the other tissues, while bone receives the largest
      fraction of hind-limb blood flow. The higher perfusion rate to bone may by due to
      a high rate of hematopoiesis in late gestation, whereas muscle flow may be lower
      than that reported immediately after birth because of limited limb movement and
      lack of shivering thermogenesis. There were no significant differences in tissue
      weights between the limb in which femoral arterial and lateral tarsal venous
      catheters were implanted (nonstudy limb) and the leg that had smaller diameter
      catheters placed in the pudendoepigastric artery and vein (study limb). However,
      nonstudy limb blood flow was 13.4 +/- 1.8% less than in the study limb, although
      the flow distribution to hind-limb tissues was not different between the two
      limbs. This suggests that the longer, larger diameter catheters inserted into the
      nonstudy limb had an adverse effect on hind-limb blood flow but not on overall
      limb growth or blood flow distribution. More attention should be paid to the
      effects of chronic fetal vascular catheterization on the tissues or organs
      normally perfused by the catheterized vessel.

PMID- 9028588
TI  - United we stand, divided we fall!

PMID- 9028589
TI  - CVMA survey questions.

PMID- 9028590
TI  - Crisis in our midst.

PMID- 9028591
TI  - The Brucellosis Research Network of the United Nations University/Biotechnology
      in Latin America and the Caribbean Program.

PMID- 9028593
TI  - Use of a clinical sepsis score for predicting bacteremia in neonatal dairy calves
      on a calf rearing farm.
AB  - In human, equine, and bovine neonates, early diagnosis of bacteremia remains a
      challenge for the internist. The objective of this study was to develop a
      predictive model for risk of bacteremia, based on a clinical evaluation system
      called the clinical sepsis score. Blood from 90 ill calves, 1- to 14-days-old
      from a calf-raising farm in the San Joaquin Valley of California was cultured.
      The calves were also scored according to a clinical score for hydration status,
      fecal appearance, general attitude, appearance of scleral vessels, and umbilical
      abnormality. Age, rectal temperature, heart rate, respiratory rate, and presence
      or absence of a focal site of infection were recorded. Prevalence of bacteremia
      was 31% (28/90). A logistic regression model indicated that high clinical score,
      presence of a focal infection, and increased age were associated with an
      increased risk of bacteremia in ill calves (P < 0.06). Calves for which the model
      predicted bacteremia with a probability > or = 40.8% were considered bacteremic,
      yielding acceptable sensitivity (75%) and specificity (71%) estimates. The
      predictive model was validated through a 2nd sampling of 100 calves (79 ill
      calves and 21 controls), of which 17 calves were bacteremic. The classification
      was 75% correct using the model, with an estimated sensitivity of 76% and
      specificity of 75%. Overall, results indicated that the model could be a useful
      tool for predicting bacteremia in ill calves in a clinical setting.

PMID- 9028592
TI  - Bacteriological culture of blood from critically ill neonatal calves.
AB  - The objectives of this study were to estimate the prevalence of bacteremia in
      critically ill, neonatal calves with severe diarrhea or depression, and to
      describe the variety of bacteria involved. Two studies were conducted in the
      summers of 1991 and 1993 involving 190 neonatal calves, 1-day to 19-days-old.
      Bacteremia was detected by blood culture in 31% (28/90) of calves in study 1, and
      in 24% (19/79) of ill calves and 0% (0/21) of control calves in study 2. Bacteria
      cultured from blood included Escherichia coli (51% of all isolates), other gram
      negative enterics (25.5%), gram-negative anaerobes (5.9%), gram-positive cocci
      (11.8%), and gram-positive rods (5.9%). Among clinically ill calves, the average
      age was significantly lower in the blood culture-negative group (5.5 d) than in
      the blood culture-positive group (7.5 d) (P = 0.004). Mean serum IgG
      concentration was significantly (P = 0.0001) lower in blood culture-positive
      calves (1.146 g/L) than in blood culture-negative calves (3.077 g/L). The
      mortality rate was significantly (P < 0.0001) higher in the blood culture
      positive group (57.4%) than in the blood culture-negative group (15.1%).
      Bacteremia appeared to be a frequent entity in this particular rearing situation.
      Early recognition of the problem, as well as appropriate treatment, may be
      beneficial in increasing survival rates. Results also support the need to address
      the failure of passive transfer of maternal antibodies to prevent bacteremia in
      calves.

PMID- 9028594
TI  - Malignant histiocytosis in a Bernese mountain dog presenting as a mandibular
      mass.
AB  - A Bernese mountain dog was evaluated because of a gingival mass, multiple
      abdominal masses, and a pulmonary mass. Malignant histiocytosis was diagnosed
      based on cytological examination of splenic and bone marrow aspirates and
      histological examination of a bone marrow biopsy and the gingival mass. The case
      demonstrates that malignant histiocytosis is difficult to diagnose due to the
      variety of histiocytic disorders.

PMID- 9028595
TI  - Removal of a nasal polyp in a standing horse.
AB  - Diagnosis and removal of a nasal polyp in a horse using standing chemical
      restraint and readily available equipment are described. Histopathology of the
      polyp and differential diagnoses are discussed.

PMID- 9028596
TI  - Haemobaphes disphaerocephalus, an accidental parasite of seawater pen-reared
      Atlantic salmon.
AB  - Gill infections by the parasitic copepod Haemobaphes disphaerocephalus (family
      Pennellidae) were observed on a few Atlantic salmon reared at 2 seawater netpen
      sites in British Columbia. This is the first report of this parasite affecting
      salmonids. The terminal holdfast penetrated into a branchial artery and was
      associated with anemia.

PMID- 9028597
TI  - Fracture of the 7th cervical and 1st thoracic vertebrae presenting as radial
      nerve paralysis in a horse.

PMID- 9028598
TI  - Riemerella anatipestifer infection of domestic ducklings.

PMID- 9028599
TI  - Isolation of Streptococcus suis from a young wild boar.

PMID- 9028600
TI  - Isolation of Abiotrophia spp. with Staphylococcus aureus in a case of mastitis in
      a cow.

PMID- 9028624
TI  - Assessment of clinical enzyme methodology: a probabilistic approach.
AB  - A number of techniques are available to assess the clinical value of enzyme
      methodologies including regression and discriminant analyses, expert systems,
      neural networks, and probabilistic. Each has its adherents but the probabilistic
      approach appears to be the most commonly used technique. This approach uses the
      fourfold contingency table that categorises subjects by both the presence or
      absence of the target disease-as defined by a gold standard test- and by a test
      result being above or below a chosen decision threshold. From this classification
      can be defined the test's sensitivity and specificity. By altering the decision
      threshold across the entire range of test values a series of
      sensitivity:specificity pairs can be tabulated. These may be plotted as 1
      specificity (or false positive rate or fraction) versus sensitivity (or true
      positive rate or fraction) to create a receiver operator characteristic (ROC)
      curve. ROC curves can provide the accuracy of the test (the area under the curve
      with associated confidence intervals), the rule-in and rule-out decision
      thresholds, and the clinical power of the test (likelihood ratio). However, a
      review of three years' publications in a peer-reviewed journal indicated that
      much of this essential data is usually absent. It is argued that such
      publications should include the decision thresholds used, the area under the
      curve and its standard error, a statistical assessment of the difference between
      two or more ROC plots, the rule-in and rule-out decision thresholds (indicating
      if these change with time after the onset of disease), and the relevant
      likelihood ratios.

PMID- 9028623
TI  - Gene transfer technologies for the production of enzyme and protein reference
      materials.
AB  - To maintain the success of recommended methods and to allow comparison among
      various methods of enzyme analysis, enzyme reference materials are required,
      having catalytic properties as close as possible to those of the corresponding
      human enzymes. Though human sources are preferable, ethical reasons require the
      extraction and purification from animal tissues. By providing theoretically
      unlimited amounts of material, gene transfer technologies and mass culture can
      overcome the need of human or mammalian tissues. We have used these technologies
      to produce human gamma-glutamyltransferase (GGT) and pancreatic lipase (PL) in
      various types of host cells. Different strategies were tested, especially for
      GGT, depending on the inherent properties and requirements of the human enzyme.
      Expression and purification protocols were optimized, yielding good amounts of
      recombinant enzymes which share many physico-chemical and catalytic features with
      their natural counterparts. Kinetic constants and catalytic behavior were very
      similar, demonstrating the usefulness of these products as reference materials.
      We assume recombinant DNA technologies could be successfully applied to most
      enzymes or proteins assayed in clinical chemistry laboratories.

PMID- 9028625
TI  - Multivariate discriminant analysis of biochemical parameters for the
      differentiation of clinically confounding liver diseases.
AB  - We describe a series of studies on the contribution of laboratory medicine to the
      differential diagnosis of clinically confounding diseases in the field of chronic
      hepatobiliary diseases. Ascitic cholesterol and lactate dehydrogenase (LD),
      selected by multivariate discriminant analysis (MDA) from a multitude of serum
      and ascitic analytes, correctly classified 100% of patients with malignant
      ascites or non-malignant ascites. In addition, ascitic pseudouridine
      differentiated hepatocarcinoma (HC) from cirrhotic ascites with a diagnostic
      effectiveness (overall discrimination power) of 90%. A panel of analytes
      constituted by serum gamma-glutamyltransferase (GGT), the GGT isoenzyme complexed
      with low- and very low-density lipoprotein, aspartate aminotransferase, copper,
      hepatic alkaline phosphatase (AP), the LD-5 isoenzyme and alpha-fetoprotein
      (AFP), selected by the MDA, correctly classified 93% of about 200 cases of
      cirrhosis or HC. Finally, MDA also identified an equation, based on serum values
      of the LD-4/LD-5 and carcinoembryonic antigen/AFP ratios, AP and iron that
      correctly classified 96% of HC or secondary liver neoplasia cases in 100
      patients. This approach based on panels of analytes selected by a sophisticated
      statistical analysis is a rapid and non-invasive contribution to the differential
      diagnosis of chronic liver disease including neoplasia.

PMID- 9028626
TI  - Ethanol metabolism, cirrhosis and alcoholism.
AB  - Alcohol-induced tissue damage results from associated nutritional deficiencies as
      well as some direct toxic effects, which have now been linked to the metabolism
      of ethanol. The main pathway involves liver alcohol dehydrogenase which catalyzes
      the oxidation of ethanol to acetaldehyde, with a shift to a more reduced state,
      and results in metabolic disturbances, such as hyperlactacidemia, acidosis,
      hyperglycemia, hyperuricemia and fatty liver. More severe toxic manifestations
      are produced by an accessory pathway, the microsomal ethanol oxidizing system
      involving an ethanol-inducible cytochrome P450 (2E1). After chronic ethanol
      consumption, there is a 4- to 10-fold induction of 2E1, associated not only with
      increased acetaldehyde generation but also with production of oxygen radicals
      that promote lipid peroxidation. Most importantly, 2E1 activates many xenobiotics
      to toxic metabolites. These include solvents commonly used in industry,
      anaesthetic agents, medications such as isoniazid, over the counter analgesics
      (acetaminophen), illicit drugs (cocaine), chemical carcinogens, and even vitamin
      A and its precursor beta-carotene. Furthermore, enhanced microsomal degradation
      of retinoids (together with increased hepatic mobilization) promotes their
      depletion and associated pathology. Induction of 2E1 also yields increased
      acetaldehyde generation, with formation of protein adducts, resulting in antibody
      production, enzyme inactivation, decreased DNA repair, impaired utilization of
      oxygen, glutathione depletion, free radical-mediated toxicity, lipid
      peroxidation, and increased collagen synthesis. New therapies include adenosyl-L
      methionine which, in baboons, replenishes glutathione, and attenuates
      mitochondrial lesions. In addition, polyenylphosphatidylcholine (PPC) fully
      prevents ethanol-induced septal fibrosis and cirrhosis, opposes ethanol-induced
      hepatic phospholipid depletion, decreased phosphatidylethanolamine
      methyltransferase activity and activation of hepatic lipocytes, whereas its
      dilinoleoyl species increases collagenase activity. Current clinical trials with
      PPC are targeted on susceptible populations, namely heavy drinkers at
      precirrhotic stages.

PMID- 9028627
TI  - Support of the diagnosis of pancreatitis by enzyme tests--old problems, new
      techniques.
AB  - Computerized tomography and ultrasound are helpful in the diagnosis of acute
      pancreatitis. The procedures, however, are not always available and so laboratory
      tests continue to play an important role. Serum amylase measurement is the most
      widely used test, despite its lack of sensitivity (75-92%) and specificity (20
      60%). A cut-off point of 3-6 times the upper reference limit increases the
      specificity greatly, but at the expense of sensitivity. A method using
      chloronitrophenyl-maltotrioside as substrate has recently been rejected by the
      IFCC. A method using ethylidene-protected 4-nitrophenyl-maltoheptaoside and a new
      alpha-glucosidase has emerged as the method of choice. Amylase isoenzyme
      determinations have higher specificity than total amylase measurements. Serum
      lipase methods are more sensitive and specific, but methodological problems
      persist. Cationic trypsin-1 measurements yield high sensitivity but low
      specificity. Elastase-1 is claimed to correlate best with the clinical symptoms.
      Reasons for the widely differing reports on sensitivity and specificity of tests
      for pancreatitis are discussed.

PMID- 9028629
TI  - Individual prostate-specific antigen (PSA) forms as prostate tumor markers.
AB  - Prostate-specific antigen (PSA) is a kallikrein-like serine protease mainly
      expressed in the human prostate. It is responsible for the proteolysis of the gel
      forming proteins in human semen. Two major extracellular protease inhibitors,
      alpha-1-antichymotrypsin (ACT) and alpha-2-macroglobulin (AMG) may inactivate PSA
      escaping from the prostate. The predominant immunodetected form of PSA in serum
      is complexed to ACT but PSA exists also in a free non-complexed form despite the
      large excess of inhibitors. The concentrations of PSA in serum are normally less
      than 4 micrograms/l. but elevated concentrations are found in a majority of
      patients with prostate cancer (CAP) and the analysis of PSA in serum has become
      invaluable in the detection and monitoring of patients with CAP. However, it is
      not an ideal tumor marker in the sense that there are CAP patients with normal
      PSA concentrations in serum and patients with benign hyperplasia of the prostate
      (BPH) with elevated PSA concentrations. Analysis of the various PSA forms in
      serum attracts much interest as there is a higher proportion of PSA in complex
      with ACT in patients with CAP than in those with BPH. Optimal combinations of
      monoclonal antibodies have been used to design sensitive noncross-reacting
      immunoassays for the detection of free PSA, PSA-ACT complexes and the detection
      of both free PSA and PSA complexes in an equimolar fashion (i.e. total PSA).
      Several studies have demonstrated that the analysis of the proportions of the
      free-to-total PSA in serum may increase the diagnostic specificity by 15-20%
      without significant loss in the sensitivity for detection of CAP.

PMID- 9028628
TI  - Cardiac troponin I and troponin T: are enzymes still relevant as cardiac markers?
AB  - Creatine kinase (CK) MB and lactate dehydrogenase (LDH) isoenzyme 1 are not heart
      specific. By contrast, the regulatory proteins troponin I and troponin T are
      expressed in three different isoforms, one for slow-twitch skeletal muscle
      fibers, one for fast-twitch skeletal muscle fibers, and one for cardiac muscle
      (cTnI, cTnT). cTnI and cTnT are usually not detectable in patients without
      myocardial damage, which is a prerequisite for high diagnostic performance. After
      acute myocardial infarction (AMI) cTnI, cTnT, and CKMB mass have a comparable
      early sensitivity. cTnI and cTnT usually peak in parallel except for patients
      without reperfusion in whom cTnI peaks about 1 day and cTnT approximately 3-4
      days after onset of AMI. Both stay increased for at least 4-5 days. cTnT tends to
      stay increased longer than cTnI. Because the sensitivities of cTnI and cTnT for
      myocardial injury are comparable, their specificities are the main topic of
      current debate. Recent reports on mismatches of cTnI and cTnT in patients with
      renal failure and myopathy without other evidence for myocardial injury suggest
      that cTnT could be reexpressed similar to CKMB and LDH-1 in chronically damaged
      human skeletal muscle. In contrast to cTnT, CKMB, and LDH-1, cTnI is not
      expressed in skeletal muscle during fetal development. So far, an increase in
      cTnI has been reported only after myocardial damage. Because of currently higher
      costs, troponin measurement should be restricted at present to clinical settings
      that really require their high specificity. Based on its distinct functional
      association with the metabolism of acute ischemic myocardium and according to
      initial clinical results, glycogen phosphorylase isoenzyme BB is a promising
      enzyme for the early detection of ischemic myocardial damage.

PMID- 9028630
TI  - Physicochemical and pathophysiological factors in the release of membrane-bound
      alkaline phosphatase from cells.
AB  - Alkaline phosphatase is bound to cell membranes by a glycan phosphatidylinositol
      anchoring domain. The structure of this domain and ways in which it may be
      cleaved by chemical and enzymatic means provide a basis for understanding the
      solubilization of alkaline phosphatase from tissues in vitro and in vivo and the
      generation of isoforms.

PMID- 9028631
TI  - Regulation of dopamine-1A (D1A) receptor gene transcription.
AB  - The D1A receptor is expressed primarily in the brain and kidney. The D1A receptor
      gene has been cloned from human, rat and pig and is organized similarly in each
      species. The 5' flanking region of the D1A receptor gene is high in GC content,
      is TATA box-less and contains multiple Sp1 binding sites. Comparison and
      alignment of the nucleotide sequences within the 5' flanking and 5' untranslated
      regions of each gene indicates that the highest sequence identity is in the area
      centered approximately 100 bases upstream from the transcription start site.
      There are numerous binding sites for transcription factors, including Sp1 and AP
      2, in the 5' flanking region. Approximately 200 bases upstream is a conserved
      cAMP regulatory element-like sequence. The conserved position of certain cis
      acting elements in each gene suggests that the essential elements for regulated
      expression of the D1A receptor gene are contained within the first 300 bases of
      the 5' flanking region.

PMID- 9028632
TI  - Transgenic mice to study the role of dopamine receptors in cardiovascular
      function.
AB  - Dopamine, an intrarenal regulator of sodium transport, is important in the
      pathogenesis of hypertension. The transduction of D1-like receptors in renal
      proximal tubules is defective in animal models of genetic hypertension. The
      defect is associated with an impaired regulation of proximal tubular sodium
      transport and cosegregates with hypertension in rats. Moreover, mice lacking one
      or both D1A receptor alleles develop hypertension. Extrasynaptic D3 receptors in
      renal tubules and juxtaglomerular cells may also regulate renal sodium transport
      and renin secretion while presynaptic D3 receptors may act as autoreceptors to
      inhibit neural norepinephrine release. Mice lacking one or both D3 alleles have
      elevated systolic blood pressure and developed diastolic hypertension. Although
      basal urine flow, sodium excretion, and glomerular filtration rate are similar,
      mice homozygous to the D3 receptor have an impaired ability to excrete an acute
      saline load compared to heterozygous and wild type mice. These studies suggest
      that abnormalities in dopamine receptor genes or their regulation may lead to the
      development of hypertension via different pathogenetic mechanisms.

PMID- 9028633
TI  - Light microscope autoradiography of peripheral dopamine receptor subtypes.
AB  - Radioligand binding assay techniques associated with light microscope
      autoradiography were used for investigating the pharmacological profile and the
      micro anatomical localization of peripheral dopamine receptor subtypes. In
      systemic arteries, the predominant dopamine D1-like receptor belongs to the D5
      (or D1B) subtype. It is located within smooth muscle of the tunica media. In
      pulmonary arteries, dopamine D1-like receptors have primarily an endothelial
      localization and belong to the dopamine D1 (or D1A) receptor subtype. Both
      systemic and pulmonary arteries express a dopamine D2-like receptor belonging to
      the D2 receptor subtype. It has a prejunctional localization in the majority of
      vascular beds investigated. In cerebral, coronary and mesenteric arteries, it has
      also an endothelial localization. In the heart, a dopamine D4 receptor was
      identified. It is expressed by atrial tissue and has a widespread distribution
      overall atrial musculature. The kidney expresses both dopamine D1-like and D2
      like receptors. Renal dopamine D1-like receptors have a vascular and tubular
      localization. The majority of these sites belongs to the D5 receptor subtype. A
      smaller D1 receptor population has primarily a tubular localization. Renal
      dopamine D2-like receptors belong to the dopamine D3 subtype and in lesser
      amounts to the D2 and D4 receptor subtypes. Renal dopamine D3 receptor has to a
      greater extent a tubular localization, whereas the D4 receptor is located within
      glomerular arterioles. The above results suggest that radioligand binding assay
      and autoradiographic techniques, if performed in the presence of compounds
      displaying specific receptor subtype selectivity, may contribute to characterize,
      mainly from a quantitative point of view, peripheral dopamine receptors.

PMID- 9028634
TI  - Renal and intestinal autocrine monoaminergic systems: dopamine versus 5
      hydroxytryptamine.

PMID- 9028635
TI  - Expression of dopamine receptors in immune organs and circulating immune cells.
AB  - The existence of dopamine (DA) D1- and D2-like receptors in the rat and pigeon
      thymus and in human peripheral blood lymphocytes was investigated. The selective
      D1-like antagonist [3H]-SCH 23390 was used as a ligand of DA D1-like receptors
      (D1 and D5 sites). Pharmacological analysis suggests that binding of [3H]-SCH
      23390 to sections of thymus and to human peripheral blood lymphocytes belongs
      mainly to the dopamine D5 receptor subtype. Light microscope autoradiography,
      performed in sections of rat and pigeon thymus, revealed that these receptors are
      located primarily in the cortical layer. DA D2-like receptors (D2, D3 and D4
      sites) were studied in sections of rat thymus and in peripheral blood lymphocytes
      by using the putative DA D3 receptor agonist [3H]-7-OH-DPAT as a ligand. Both rat
      and pigeon thymus and human peripheral blood lymphocytes express a putative DA D3
      receptor. These data are in agreement with recent molecular biology studies
      performed in human peripheral blood lymphocytes. The demonstration of different
      subtypes of DA receptors in a primary immune organ such as the thymus and in
      circulating immune cells supports the hypothesis of an involvement of DA in the
      control of immune function.

PMID- 9028636
TI  - Short-term vs. sustained inhibition of proximal tubule Na,K-ATPase activity by
      dopamine: cellular mechanisms.
AB  - Dopamine (DA) produces a natriuresis attributed in part to inhibition of Na,K
      ATPase activity (NKA) in the proximal tubule (PCT), and impairment in this
      inhibition has been linked to several forms of hypertension in animals. Here we
      examined whether the intracellular signaling mechanisms involved are the same in
      the early and late phases of this phenomenon. DA (1 microM) inhibited NKA
      similarly after 15 min (by 38%) or 180 min (by 36%) incubation, taken to
      represent short-term (ST) and sustained (Sd) pump regulation, respectively.
      Calphostin C, a specific inhibitor of protein kinase C (PKC), completely blocked
      the ST action of DA on NKA, whereas IP20, a specific inhibitor of protein kinase
      (PKA), had no effect. In contrast, IP20 completely abolished the Sd (180 min)
      inhibition by DA, whereas calphostin C had only a partial or variable effect. The
      DA-1 agonist fenoldopam (which does not activate PKC but increases cAMP) alone
      failed to inhibit the pump at 180 min (as it does also in the short-term in PCT),
      suggesting that ST inhibition is required for the Sd effect to occur.
      Furthermore, PTH1-34, a known ST inhibitor of NKA suppressed the pump at 180 min
      (by 46%), but unlike in the short-term, this effect was completely prevented by
      IP20. In contrast, PTH3-34, which does not stimulate adenylyl cyclase or activate
      PKA, caused only a small (19%) and variable Sd inhibition. In conclusion, short
      term inhibition of the PCT pump by dopamine is mediated via PKC, whereas the
      sustained inhibition requires the PKA pathway in addition to the ongoing PKC
      mediated effect.

PMID- 9028637
TI  - Regulation of sodium transport by endogenous dopamine production in proximal
      tubular and OK cells.
AB  - Inhibition of AADC for several hours increases the activity and mass of NaKATPase
      in proximal tubular basolateral membranes and reduces phosphate (P1) and citrate
      excretion, but has only a small effect on Na excretion. The reduction in citrate
      excretion is consistent with the observed increase in brush border Na+/H+
      exchange. Thus, in Na replete rats, endogenous D inhibits Na entry into proximal
      tubular cells, through cotransport with Pi and exchange with H+, and inhibits
      exit through the Na pump. Tonic D inhibition of NaKATPase and Na+/H+ antiporter
      activity is not found in the SH rats' kidneys, which have defective linkage of
      proximal tubular D receptors to adenylate cyclase. The inhibitory action of
      endogenous D on Pi reabsorption is retained in SHR kidneys. This suggests that
      different signaling systems are responsible for the effects of D on NaPi
      transport and Na+/H+ exchange. In OK cells D inhibits NaPi cotransport (Ki 0.2
      microM). The D effect is not blocked by cAMP, adenylate cyclase, PKA or PKC
      inhibitors. Thus it appears that D regulates NaPi transport by a non-cAMP, non
      PKC mechanism and is a homeostatic regulator of phosphate reabsorption by SHR.

PMID- 9028638
TI  - Dopamine D3 receptors in rat juxtaglomerular cells.
AB  - D2-like receptors in the kidney have been suggested to be important in the
      regulation of renin release but the D2-like subtype(s) expressed in
      juxtaglomerular (JG) cells is not known. Therefore, we determined which of the D2
      like family of dopamine receptors is located in primary cultures of rat
      juxtaglomerular (JG) cells. Reverse transcriptase-polymerase chain reaction (RT
      PCR) identified D3 and D4 but not D2Long mRNA in JG cells (n = 3). D3 receptor
      function was demonstrated by a concentration-dependent inhibition of forskolin
      stimulated cAMP production by LY-171555 (a non-selective D2-like receptor
      agonist) and PD-128593 (a partially selective D3 agonist) (n = 3-7/group). The
      stimulatory action of LY-171555 and PD-128593 we blocked by the non-selective D2
      like antagonist YM-09151. We conclude that D3 and D4 dopamine receptor subtypes
      are expressed in JG cells; the receptor subtype linked to the inhibition of cAMP
      in JG cells remains to be established.

PMID- 9028639
TI  - Preferential release of renal dopamine into the tubule lumen: effect of chronic
      sodium loading.
AB  - Dopamine (DA), produced by the renal proximal tubule, has been demonstrated as an
      intrarenal paracrine hormone mediating diuresis and natriuresis. The precise
      mechanism by which DA exerts its cell-to-cell action is not fully understood. In
      the present study, renal interstitial (RIF) DA (by in vivo microdialysis) and
      urinary DA excretion (UDAV) were compared in anesthetized rats on either normal
      (0.28% NaCl, NS) or high (4.0% NaCl, HS) sodium balance (n = 9 in each group).
      Urine flow (UV) and sodium excretion (UNaV) in HS were greater than in NS rats
      (UV 7.2 +/- 0.6 vs 3.8 +/- 0.3 microliters/min, P < 0.01; UNaV 497 +/- 66 vs 265
      +/- 27 nmol/min, P < 0.01). In rats on both NS and HS balance, UDAV was
      significantly higher than RIF DA (420 +/- 37 vs 3.68 +/- 0.49 pg/min in the NS
      rat; 601 +/- 68 vs 1.25 +/- 0.36 pg/min in the HS rat, both P < 0.01). UDAV was
      increased in HS compared with NS rats (601 +/- 68 vs 420 +/- 37 pg/min, P <
      0.05). In contrast, RIF DA was significantly lower in HS than NS rats (1.25 +/-
      0.36 vs 3.68 +/- 0.49 pg/min, P < 0.01). In conclusion, chronic sodium loading
      increased renal DA production and release predominantly into the tubular lumen
      rather than the peritubular interstitial space of the kidney. These results
      indicate that DA originating from proximal tubule cells has a direct tubule
      action in the control of sodium excretion.

PMID- 9028640
TI  - Comparative hypertensionology-renal dopaminergic activity in experimental
      hypertensive rats.
AB  - In our laboratory, it had been found that the renal natriuretic and depressor
      systems are suppressed in essential hypertension, and that suppression of the
      dopaminergic system may be primary and dominant in this condition. Moreover,
      close relationships among the renal dopamine, kallikrein-kinin, and prostaglandin
      systems have also been found. Therefore, we attempted to evaluate the
      pathogenetic and pathophysiological role of renal dopamine in connection with
      renal kallikrein-kinin and prostaglandin systems in various experimental
      hypertensive models. Two kidney 1 clip hypertensive rats (2K1C), 5/6 reduced
      renal mass hypertensive rats (5/6 RRM), deoxycorticosterone acetate-salt
      hypertensive rats (DOCA-salt), spontaneously hypertensive rats/Izumo (SHR/Iz),
      Dahl salt sensitive hypertensive rats/John Rapp (Dahl/Jr), Dahl/Iwai (Dahl/Iw),
      and respective controls were employed in this study. Urinary excretions of free
      dopamine (uDA), kallikrein (uKAL), and prostaglandin E2 (uPGE2) were measured
      before, during and after treatment in each of these hypertensive models. In these
      experimental hypertensive models, renal dopamine in DOCA-salt and SHR/Iz, and
      renal kallikrein in 2K1C, 5/6 RRM and two types of Dahl strains were primarily
      and dominantly suppressed in the renal natriuretic and depressor systems. Renal
      dopamine was transiently suppressed in Dahl/Jr, and PGE2 was suppressed in the
      two types of Dahl strains. Compensatory augmentation of renal kallikrein was
      found in DOCA-salt and SHR/Iz, and that of PGE2 was found in 5/6 RRM and DOCA
      salt. Although these three renal natriuretic depressor systems are suppressed in
      Dahl/Jr, the dominantly suppressed system is not renal dopamine but renal
      kallikrein. Thus, it was summarized that, 1) decreased renal dopamine production
      is important in the pathogenesis of human essential hypertension, 2) pressor
      mechanisms of experimental hypertensive rats are different from human essential
      hypertension, 3) decreased renal dopamine is important in DOCA-salt and SHR/Iz,
      4) decreased renal kallikrein is the dominant mechanism in the pathogenesis of
      2K1C, 5/6 RRM, Dahl/Jr and Dahl/Iw hypertensive rats, and 5) we have to be
      careful when considering human essential hypertension through results taken from
      experimental rat hypertensive models.

PMID- 9028641
TI  - Dopamine-1 receptor G-protein coupling and the involvement of phospholipase A2 in
      dopamine-1 receptor mediated cellular signaling mechanisms in the proximal
      tubules of SHR.
AB  - Dopamine-induced natriuretic response which results from the activation of
      tubular dopamine1 (DA1) receptors is diminished in spontaneously hypertensive
      rats (SHR). This may be a result of alterations occurring at the receptor level
      and within the cellular signaling pathway which ultimately causes inhibition of
      Na+, K(+)-ATPase. There have been reports showing that DA1 receptor induced
      inhibition of Na+, K(+)-ATPase is abolished in SHR which is due to a decreased
      activation of PLC and PKC by dopamine. Of the mechanisms, adenylyl cyclase and
      phospholipase C are two known enzymes linked to DA1 receptors via G proteins.
      Furthermore, the involvement of phospholipase A2 (PLA2) has also been reported in
      this process. However, the site of defect in DA1 receptor signaling pathway in
      SHR is still not well understood. This report will (i) review the coupling of DA1
      receptor with G proteins and their levels in Wistar Kyoto (WKY) rats and SHR and
      (ii) discuss studies dealing with the role of PLA2 in dopamine-induced inhibition
      of Na+, K(+)-ATPase in WKY rat and SHR kidneys. Fenoldopam, DA1 receptor
      selective agonist stimulated [35S]GTP gamma S binding in a concentration (10(-9)
      10(-4) M)-dependent manner in WKY rats which was attenuated in SHR. Fenoldopam
      (10 microM)-induced stimulation of [35S]GTP gamma S binding was significantly
      reduced by a DA1 receptor selective antagonist, SCH 23390 suggesting the
      involvement of DA1 receptor. Furthermore, the specific antipeptides Gs alpha, and
      Gq/11 alpha significantly blocked fenoldopam-stimulation of [35S]GTP gamma S
      binding suggesting the coupling of DA1 receptor with both the G proteins. Western
      analysis revealed a significant decrease in Gq/11 alpha but no changes in Gs
      alpha in SHR compared to WKY rats. Dopamine inhibited Na+, K(+)-ATPase activity
      in a concentration (10(-9)-10(-5) M)-dependent manner in WKY rats while it failed
      to inhibit the enzyme activity in SHR. Dopamine (10 microM)-induced inhibition in
      Na+, K(+)-ATPase activity was significantly blocked by mepacrine (a PLA2
      inhibitor) suggesting the involvement of PLA2 in dopamine-mediated inhibition of
      Na+, K(+)-ATPase. Arachidonic acid (AA), a PLA2 product, inhibited Na+, K(+)
      ATPase in a concentration (1-100 microM)-dependent manner in WKY rats while the
      inhibition in SHR was significantly attenuated (IC50: 7.5 microM in WKY and 80
      microM in SHR). Furthermore, lower concentration (1 microM) of AA stimulated the
      enzyme activity in SHR. This suggests a defect in the metabolism of AA in SHR.
      Proadifen (10 microM), an inhibitor of cytochrome P-450 monoxygenase (an
      arachidonic acid metabolizing enzyme) significantly blocked the inhibition
      produced by arachidonic acid in WKY rats and abolished the difference in
      arachidonic acid inhibition of Na+, K(+)-ATPase between WKY rats and SHR. These
      data suggest that (i) the reduced activation of G proteins following DA1 receptor
      stimulation, (ii) reduced amount of Gq/11 alpha and (iii) a defect in the AA
      metabolism may be responsible for the reduced dopaminergic inhibition of sodium
      pump activity and a diminished natriuretic response to dopamine in SHR.

PMID- 9028642
TI  - The mechanisms underlying heart stimulation by dopamine, with special reference
      to direct and indirect beta adrenoceptor stimulation.
AB  - 1. The positive chronotropic and norepinephrine-releasing effects of dopamine
      were examined in the isolated guinea pig heart, using the Langendorff model. 2.
      The released norepinephrine was estimated from the norepinephrine concentration
      measured in the post-perfusion solution using HPLC. 3. The dose-response curve
      for dopamine to stimulate the heart rate (HR) closely resembled that for the
      norepinephrine release. A selective beta 1 antagonist bisoprolol completely
      abolished the positive chronotropic effect, but did not affect the norepinephrine
      release. 4. The HR increase in response to 3 mumol/L dopamine was 54 +/- 15% (n =
      14) of the control in normal hearts. The response was decreased to 15 +/- 7% (n =
      6) by pretreatment with reserpine. 5. A D1 antagonist, SKF83742, (3 mumol/L)
      shifted the dose-response curve for the dopamine-induced norepinephrine release
      toward the right, indicating the involvement of D1-like dopamine receptors. 6.
      Voltage clamp experiments using single cells isolated from the right atrium
      revealed that dopamine is a weak partial agonist for beta adrenoceptors. Dopamine
      stimulated the L-type Ca2+ current with a threshold concentration of 3 mumol/L.
      7. These findings indicate the important role of the norepinephrine release in
      the stimulation of beta adrenoceptors by dopamine at clinically relevant
      concentrations.

PMID- 9028643
TI  - Metabolic fate of the sympathoneural imaging agent 6-[18F]fluorodopamine in
      humans.
AB  - We examined the metabolism of 6-[18F]fluorodopamine, by assaying arterial plasma
      concentrations of radioactivity, 6-[18F]fluorodopamine, and 6-[18F]fluorodopamine
      metabolites in untreated subjects or subjects given desipramine to block neuronal
      uptake of catecholamines or tyramine to displace vesicular amines. After the 3
      min 6-[18F]fluorodopamine infusion, plasma 6-[18F]fluorodopamine levels declined
      precipitously, total radioactivity declining slowly. After 30 min, the main
      identified metabolite was 6-[18F]fluorodopamine-sulfate. Desipramine attenuated
      the rapid increase in plasma 6-[18F]fluorodihydroxyphenylacetic acid levels, and
      tyramine briefly increased 6-[18F]fluorodopamine levels. Neither drug affected 6
      [18F]fluorodopamine-sulfate levels. The results indicate that soon after 6
      [18F]fluorodopamine infusion, plasma radioactivity corresponds mainly to 6
      [18F]fluorodopamine metabolites; that sympathetic nerves rapidly remove 6
      [18F]fluorodopamine, which then undergoes oxidative deamination in the neuronal
      cytoplasm and sequestration in sympathetic vesicles; and that sulfoconjugation of
      [18F]fluorodopamine occurs extraneuronally.

PMID- 9028645
TI  - Efficacy and mechanisms of dopexamine in the prevention of ischemia-reperfusion
      induced organ damage: role of oxygen free radicals.
AB  - The studies reported in this article provide evidence that several complex
      mechanisms are involved in the ability of dopexamine HCl (DPX) in preventing
      ischemia-reperfusion induced organ damage. In a canine model of hemorrhagic shock
      in which shed-blood was reinfused, DPX prevented deterioration in renal blood
      flow via an action on beta-2 and DA-1 receptors, whereas its ability to preserve
      tubular function was essentially due its agonistic effects on DA-1 receptors. In
      a different experimental model in anesthetized rats, acute generation of oxygen
      free radicals (OFR) via intravenous administration of Xanthine (X) followed by
      Xanthine Oxidase (XO) resulted in depression of circulation and death of more
      than 80% of the animals within the observation period of 120 min. Pretreatment of
      the rats with DPX significantly enhanced survival rate in a dose dependent manner
      to about 70%. Neither dobutamine nor prenalterol, which are beta-1 adrenoceptor
      agonists and like DPX, potent chronotropic and inotropic agents were effective in
      preventing OFR induced lethal toxicity. In a separate series, a selective DA-1
      receptor agonist felodopam had no protective effect and a DA-1 receptor
      antagonist SCH-23390 failed to antagonize the salutary effects of DPX. In
      contrast, salbutamol, a selective beta-2 adrenoceptor agonist significantly
      promoted the survival rate facilitated by DPX and a selective beta-2 adrenoceptor
      antagonist, ICI-558,551 significantly attenuated the survival rate. These later
      studies suggest that unlike in hemorrhagic shock, the beta-2 adrenoceptor
      agonistic properties are critical in the ability of DPX to attenuate lethal
      toxicity and these effects could be related to prevention of lipid peroxidation
      induced by oxygen free radicals.

PMID- 9028644
TI  - Dopamine and sympathoadrenal activity in man.
AB  - The sympathetic adrenal (SA) activity can be modulated by dopamine (DA) through
      D2 receptors. In man, using D2 antagonists, it has been demonstrated that
      endogenous DA plays an inhibitory modulation of the SA system during high degree
      of SA activation. D2 agonists are able to induce a decrease in norepinephrine
      (NE) release either in vitro or in vivo. This effect leads, in vivo, to a
      decrease in blood pressure (BP) and to an activation of arterial baroreceptors.
      Therefore, in vivo, the D2 mediated inhibition of epinephrine (E) release, which
      is clearly demonstrated in vitro, is overwhelmed by the baroreceptor-mediated
      activation of the splachnic nerve. As a consequence, the in vivo administration
      of D2 agonists can induce a different effect on the net peripheral sympathetic
      tone of an organ, depending on the balance between the degree of the baroreceptor
      mediated sympathetic activation and the inhibitory D2-mediated inhibition of NE
      release at the tissue level. In the present paper we investigated the in vivo
      effect of placebo (PL) or acute oral bromocriptine (BC) administration on plasma
      CA and on the cardiac sympatho-vagal balance of 7 normal volunteers, as assessed
      by power spectral analysis of heart rate (HR) variability (autoregressive
      method), either in resting or sitting position. Low frequency (LF) and high
      frequency (HF) components, both expressed in normalized units (nU), and LF/HF
      ratio were calculated. BC caused a decrease in BP, plasma NE and no change in HR
      in resting and sitting position. Plasma E increased in sitting position. At the
      heart level, after BC, we observed, during rest, an increase in LF and LF/HF
      ratio and a decrease in HF while in sitting position LF did not increase further.
      These data show that BC, while reducing BP through a decrease of plasma NE,
      increases LF/HF ratio (sympathetic tone) without any change in heart rate. These
      data seem to confirm that BC causes an inhibitory modulation of the SA system
      acting predominantly at the periphery through D2 presynaptic receptors.

PMID- 9028646
TI  - Use of dopamine in the ICU. Hope, hype, belief and facts.
AB  - Dopamine is frequently administered in the ICU to critically-ill patients. The
      widespread use of dopamine does not only involve states of distributive and
      cardiogenic (imminent) shock, but also prophylaxis for deterioration and/or
      improvement of kidney- and bowel perfusion. Although many studies have shown an
      increase of renal- and (in some studies) improvement of splanchnic circulation,
      well controlled studies have failed to demonstrate a better outcome with respect
      to renal function and/or survival of prophylactic dopamine administration.
      Furthermore, evidence exists that norepinephrine is more efficacious in fluid
      resuscitated septic shock patients to restore blood pressure than dopamine,
      without jeopardizing the renal function. It is concluded that the widespread use
      of dopamine in the ICU should be reassessed.

PMID- 9028647
TI  - The role of dopaminergic agonists in congestive heart failure.
AB  - Congestive Heart Failure is a clinical syndrome characterised by myocardial
      dysfunction and sympathetic activation. Plasma norepinephrine (NE) levels have
      been related to the poorest survival. Large-scale clinical trials have proved the
      clinical benefits of Angiotensin Converting Enzyme inhibitors in reducing the
      risk of death and hospitalisation. However, mortality remains high in the treated
      group underlining the need to explore new therapeutic approaches. Specific
      activation of peripheral dopamine receptors exerts profound hemodynamic effects
      and neurohormonal control such as peripheral and renal vasodilation, diuresis and
      natriuresis and inhibition of NE release. Z1046, a mixed D1/D2-like agonist,
      reduces peripheral and renal vascular resistance increasing renal blood flow. In
      anaesthetised dogs the compound strongly reduces plasma NE without increasing
      plasma renin activity and plasma aldosterone. The inhibition of NE could be the
      basis of Z1046 potent cardioprotective effect observed in a dog model of
      myocardial ischemia and reperfusion, in which the severity of ventricular
      arrhythmias was markedly reduced, resulting in higher survival. These findings
      suggest that chronic oral treatment with specific dopaminergic agonists is able
      to alleviate the hemodynamic burden on the myocardium, and to suppress the
      sympatho-adrenal activity.

PMID- 9028684
TI  - Glycated hemoglobin and related factors in diabetic children and adolescents
      under 18 years of age: a Belgian experience.
AB  - OBJECTIVE: To determine, in an unselected population of diabetic children and
      adolescents < 18 years of age, which HbA1c levels can be achieved, and to examine
      the relationships with insulin regimen, insulin dose, sex, diabetes duration,
      BM1, and frequency of home blood glucose monitoring (HBGM) and outpatient clinic
      attendance. RESEARCH DESIGN AND METHODS: A total of 144 unselected subjects (73
      boys and 71 girls) aged 11.8 +/- 3.7 years (mean +/- SD) were included in the
      study over a 6-month period. They had diabetes durations ranging from 5 months to
      15 years (4.0 +/- 3.0). They were followed by the same pediatric diabetologist
      and the same nurse. The yearly frequency of visits was 8.9 +/- 2.0, and the
      monthly frequency of HBGM was 111 +/- 27. Of the patients, 129 were treated with
      two daily insulin injections of an individualized mixture of rapid- and
      intermediate-acting insulins, and 15 adolescents were treated with four
      injections using the basal-bolus regimen. The patients were divided into two
      subgroups according to diabetes duration: < or = 2 years (n = 53) and > 2 years
      (n = 91), i.e., outside the honeymoon period. HbA1c was measured by a high
      pressure liquid chromatography method (normal values 3.9-5.5%). RESULTS: The mean
      +/- SD HbA1c level in the 144 children and adolescents was 6.6 +/- 1.2% using our
      method. In 62% of the patients, it was possible to obtain an HbA1c level under
      the normal mean value plus 5 SD. HbA1c was not related to sex, number of insulin
      injections, or age, i.e., it was not poorer at adolescence. The mean daily
      insulin dose was 0.9 U/kg body wt, being lower during the first 2 years of
      diabetes and reaching 1 U at adolescence. HbA1c levels were lower during the
      first 2 years of diabetes (6.2 +/- 1.0%) than afterwards (6.9 +/- 1.2%), but the
      frequencies of outpatient visits and HBGM were higher. After 2 years, HbA1c was
      negatively correlated with the frequency of HBGM. The yearly incidence rate of
      severe hypoglycemic episodes was 0.2. After the age of 13 years, BM1 was
      significantly higher in girls and in adolescents on four daily injections.
      CONCLUSIONS: In nearly two-thirds of diabetic children and adolescents, it is
      possible to obtain HbA1c levels under the normal mean plus 5 SD, which is
      considered satisfactory and close to that of the adult cohort of the Diabetes
      Control and Complications Trial (DCCT) with intensive treatment. There is no
      difference between the children on only two daily insulin injections and the
      adolescents on four injections. After 2 years of diabetes, increased frequency of
      HBGM helps reduce HbA1c levels, taking into account the "intensive" education of
      the patients and their families. Adolescent girls on four injections must pay
      attention to the risk of becoming overweight.

PMID- 9028685
TI  - Characteristics related to poor glycemic control in NIDDM patients in community
      practice.
AB  - OBJECTIVE: To identify clinical characteristics related to poor glycemic control
      in patients with NIDDM cared for by Michigan primary care physicians. RESEARCH
      DESIGN AND METHODS: This study was a cross-sectional secondary analysis of data
      from 393 NIDDM patients (mean age, 63 +/- 11 years; 54% female; 92% white) in the
      1990-1991 Michigan Diabetes in Communities II Study. We evaluated patient
      demographic, clinical, and physiological characteristics, attitudes toward
      diabetes, and self-care ability. Logistic regression was used for multivariate
      evaluation of the characteristics of those patients whose glycosylated hemoglobin
      (normal GHb 4-8%) was in the upper 25% of the study sample (GHb > 11.6%).
      RESULTS: A high meal-stimulated plasma C-peptide was associated with a lower
      likelihood of poor control (odds ratio [OR] for highest quartile vs. all others =
      0.37; 95% CI 0.23-0.58). Longer time since diagnosis (OR for each 5 years
      duration = 1.28; 95% CI 1.07-1.53), poor self-care ability (OR = 1.85; 95% CI
      1.27-2.71), and perceived absence of dietary recommendations (OR = 2.37; 95% CI
      1.11-5.08) were also independently associated with presence in the highest GHb
      quartile. Characteristics that were not significantly related to poor glycemic
      control included sex, age, obesity, educational level, exercise, self-rated
      health status, and pharmacological treatment. CONCLUSIONS: 1) Poor glycemic
      control may reflect progressive failure of islet function, although the
      independent relationships of C-peptide level and time since diagnosis are
      consistent with concepts of heterogeneous mechanisms underlying NIDDM. 2) Despite
      the important relationships of biological characteristics of NIDDM to glycemic
      control, patient attitudes and self-care ability may be useful targets for
      designing management strategies for certain poorly controlled patients.

PMID- 9028686
TI  - Measurement of plasma LDL cholesterol in patients with diabetes.
AB  - OBJECTIVE: To assess the accuracy of plasma LDL cholesterol concentrations
      estimated by the Friedewald formula and a direct immunoseparation method by
      comparison with a reference ultracentrifugation procedure in patients with
      diabetes. RESEARCH DESIGN AND METHODS: Fasting plasma samples with triglyceride
      concentrations < 4.5 mmol/l were collected from 100 patients with diabetes (28
      type I and 72 type II) and LDL cholesterol concentrations were compared by the
      three methods. RESULTS: LDL cholesterol values determined by the reference beta
      quantitation procedure were highly correlated with both the Friedewald formula (r
      = 0.96) and a direct immunoseparation method (r = 0.92). Calculated (Friedewald)
      LDL cholesterol coincided with the reference method with < 10% error in 74% of
      the total diabetic group (82% of type I and 68% of type II diabetic patients).
      However, agreement between the direct LDL cholesterol and reference methods was
      significantly less (P = 0.02), with only 44% of patients having an error of < 10%
      (52% of type I and 41% of type II diabetic patients). The direct immunoseparation
      method for LDL cholesterol showed a positive bias with increasing triglyceride
      concentrations, particularly for patients with type II diabetes. CONCLUSIONS: In
      the group of diabetic patients studied with plasma triglyceride concentrations <
      4.5 mmol/l, the Friedewald formula provided an accurate estimation of LDL
      cholesterol. The direct immunoseparation method significantly overestimated LDL
      cholesterol at triglyceride levels between 2 and 4.5 mmol/l.

PMID- 9028687
TI  - The feasibility of automated voice messaging as an adjunct to diabetes outpatient
      care.
AB  - OBJECTIVE: To determine whether automated voice messaging (AVM) systems could be
      used as an adjunct to primary care for diabetic patients, we examined whether
      patients were able to respond to AVM queries for clinical information, whether
      sufficient numbers of problems were identified to warrant the implementation of
      the service, and whether patients found the system helpful. RESEARCH DESIGN AND
      METHODS: The AVM system we examined uses specialized computer technology to
      telephone patients, communicate messages, and collect information. Sixty-five
      diabetic patients participated. Based on a review of the literature and the input
      of diabetes clinician-researchers, we developed an AVM monitoring protocol to
      inquire about patients' symptoms, glucose monitoring, foot care, diet, and
      medication adherence. Patients also were given the option to listen to health
      promotion messages and to report their satisfaction with the calls. Patients
      responded by using their touch-tone telephone keypads. RESULTS: A total of 216
      AVM calls were successfully completed, an average of 3.3 out of four calls per
      patient. Patients reported a variety of health problems that signaled the need
      for follow-up. Many patients reported not checking their blood glucose or their
      feet, and one in four reported problems with medication and diet adherence.
      Health and self-care problems varied across patient subgroups in ways suggesting
      that the AVM reports were reliable and valid. Overall, 98% of all patients
      reported that the calls were helpful, 98% reported that they had no difficulty
      responding to the calls, and 77% reported that receiving AVM calls would make
      them more satisfied with their health care. CONCLUSIONS: This study demonstrates
      that diabetic patients can respond to AVM queries and find the calls helpful.
      Such calls are a feasible strategy for identifying health and self-care problems
      that would otherwise go unnoticed by clinicians.

PMID- 9028688
TI  - Hypoglycemia: incidence and clinical predictors in a large population-based
      sample of children and adolescents with IDDM.
AB  - OBJECTIVE: To determine the frequency of moderate and severe hypoglycemia and to
      identify clinical predictors associated with its occurrence in a large population
      based sample of children and adolescents with IDDM. RESEARCH DESIGN AND METHODS:
      A total of 657 patients (age: 12.1 +/- 4.4 years, mean +/- SD) were included in
      the study, yielding 1,449 patient-years of data. A prospective assessment of
      severe hypoglycemia (an event resulting in a seizure or coma) and moderate
      hypoglycemia (an event requiring assistance of another, excluding severe
      episodes) was made over a 3-year period. Patients and caregivers detailed
      episodes of significant hypoglycemia (moderate and severe events) and these were
      recorded at each 3-month clinic visit along with HbA1c. Data were analyzed using
      generalized estimating equation models fitted with the exchange correlation
      structure. RESULTS: The overall incidence of severe events was 4.8/100 patient
      years and of moderate events was 13.1/100 patient-years. Over 3 years, severe
      events occurred in 8.5% of children and moderate events occurred in 26.9%.
      Significant hypoglycemia was rare in the first 12 months after diagnosis. Rates
      of hypoglycemia were increased in children < 6 years of age versus > 6 years of
      age (40.9 vs. 16.6/100 patient-years, age < or = 6 years vs. age > 6 years, P <
      0.001). Rates of hypoglycemia doubled when HbA1c fell below 8%, and children with
      HbA1c < 7% had a threefold increase in both moderate and severe hypoglycemia
      (e.g., severe episodes 14.9 vs. 4.1/100 patient-years, HbA1c < or = 7% vs. HbA1c
      > 7%, P < 0.001). Most severe events were seizures, and 75% of them occurred at
      night. The majority of events were related to missed meals or increased activity.
      However, in 38% no predisposing factor was evident. CONCLUSIONS: Newly diagnosed
      children appear to be protected from severe hypoglycemia. Rates increase with
      lower glycated hemoglobin, especially when mean HbA1c is < 8.0%. Younger
      children, who may be more susceptible to the adverse effects of neuroglycopenia,
      are at a particular risk of significant hypoglycemia.

PMID- 9028689
TI  - Lifestyle changes may reverse development of the insulin resistance syndrome. The
      Oslo Diet and Exercise Study: a randomized trial.
AB  - OBJECTIVE: To compare and assess the single and joint effect of diet and exercise
      intervention for 1 year on insulin resistance and the development leading toward
      the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: An unmasked,
      randomized 2 x 2 factorial intervention trial was applied with a duration of 1
      year for each participant. The trial comprised 219 men and women with diastolic
      blood pressure of 86-99 mmHg, HDL cholesterol < 1.20 mmol/l, triglycerides > 1.4
      mmol/l, total cholesterol of 5.20-7.74 mmol/l, and BMI > 24 kg/m2. Participants
      were randomly allocated to diet group (n = 35), diet and exercise group (n = 67),
      exercise group (n = 54), and control group (n = 43). The diet included increased
      intake of fish and reduced total fat intake. The exercise program entailed
      supervised endurance exercise three times a week. Baseline cross-sectional
      changes and 1-year changes in insulin resistance, fasting serum levels of
      insulin, C-peptide, proinsulin, glucose, and lipids as well as weight, mean blood
      pressure, and plasminogen activator inhibitor 1 (PAI-1) values were recorded.
      RESULTS: The cross-sectional results at baseline showed significant correlations
      between the calculated insulin resistance and BMI (r = 0.54) and correlations
      between the mean blood pressure (mBP) (r = 0.26) and PAI-1 (r = 0.40). The 1-year
      diet intervention gave a significant decrease in the calculated insulin
      resistance from 4.6 to 4.2 and a positive correlation between the changes in
      insulin resistance and changes in BMI (r = 0.40). The diet and exercise
      intervention also led to significantly decreased insulin resistance (from 5.0 to
      4.0). The exercise intervention did not significantly change insulin resistance.
      CONCLUSIONS: The cross-sectional and 1-year intervention results supported each
      other and underscored the important connection between increased BMI and the
      development leading toward the insulin resistance syndrome.

PMID- 9028690
TI  - Cognitive function in younger type II diabetes.
AB  - OBJECTIVE: To examine central nervous system involvement as a possible
      complication of diabetes by performing a comprehensive neuropsychological
      evaluation of relatively young (age < 55 years) NIDDM patients and a group of
      control subjects. RESEARCH DESIGN AND METHODS: A cross-sectional comparative
      study of 28 patients, with duration of diabetes 5-18 years (mean +/- SD +/- 3.2
      years), screened for acceptable glycemic control and absence of hypoglycemia on
      the day of examination, compared with 28 demographically similar, nondiabetic
      control subjects. Neuropsychometric tests performed were Mini-Mental Status
      Examination (MMSE), Neurobehavioral Cognitive Status Examination (NCSE), and P300
      latencies (endogenous evoked potentials). RESULTS: Seven (25.0%) patients
      reported history suggestive of cognitive impairment during day-to-day activities,
      and 17 (60.7%) had distal symmetrical polyneuropathy. Average P300 latencies were
      significantly delayed among the diabetic patients compared with the control
      subjects (349.5 +/- 28.2 vs. 312.9 +/- 19.3 ms; t = 5.68, P < 0.001). Although
      there was no significant difference in MMSE scores, compared with control
      subjects significantly more patients had impairment in NCSE tests of attention
      (chi 2 = 7.38, P < 0.01), repetition (chi 2 = 4.073, P < 0.05), and memory (chi 2
      = 5.83, P < 0.05), while there was no significant difference in tests of
      comprehension, naming, construction, and calculation. Duration of diabetes, HbA1c
      levels, and the presence of distal symmetrical polyneuropathy among patients each
      did not correlate with any of the parameters of cognitive function evaluated.
      Higher blood glucose levels during the electrophysiological testing were
      associated with less delay in P300 latencies among the patients. CONCLUSIONS:
      Central nervous system impairment, manifesting as mild impairments in certain
      cognitive skills, should be recognized as a possible complication of long
      standing NIDDM, even in relatively younger individuals.

PMID- 9028691
TI  - Psychiatric disorders in youths with IDDM: rates and risk factors.
AB  - OBJECTIVE: To determine prevalence rates, associated features and risk factors
      for psychiatric disorders subsequent to the diagnosis of IDDM in youths. RESEARCH
      DESIGN AND METHODS: Using a longitudinal, naturalistic design, 92 youths from 8
      to 13 years old at onset of IDDM were followed from their initial diagnosis. They
      were repeatedly assessed by semistructured interview and diagnosed by operational
      criteria. RESULTS: By the 10th year of IDDM and the mean age of 20 years, an
      estimated 47.6% of the sample developed psychiatric disorder. Major depressive,
      conduct, and generalized anxiety disorders were the most prevalent, and major
      depression had a significantly higher estimated rate (27.5%) than each other
      disorder. The highest incidence rates were during the 1st year of the medical
      condition. Initial maternal psychopathology increased the risk of psychiatric
      disorder in the subjects, and maternal depression was a specific risk factor for
      depression in the subjects. Earlier psychiatric disorder in the subjects also
      increased the risk of later disorder. CONCLUSIONS: The results converge with
      findings from other studies, suggesting elevated psychiatric morbidity in
      contemporary samples of young people with IDDM. The morbidity partly reflects the
      high incidence of major depression in adolescence and generalized anxiety
      disorder in young adulthood. Monitoring the psychological status of young
      patients and their mothers may help to identify diabetic children at risk for
      psychiatric disorder and facilitate prevention or treatment efforts. Monitoring
      may be particularly beneficial during the 1st year of the IDDM.

PMID- 9028692
TI  - Major depressive disorder in youths with IDDM. A controlled prospective study of
      course and outcome.
AB  - OBJECTIVE: To determine whether IDDM affects the course of major depressive
      disorder (MDD) in youths. RESEARCH DESIGN AND METHODS: The study samples include
      24 youths with IDDM (of a group of 92) who developed MDD during a longitudinal
      follow-up of 10 years, on average, since onset of the medical condition, and 30
      depressed psychiatric control subjects, matched on relevant variables. Both
      groups were repeatedly assessed by semistructured interviews and diagnosed by
      operational criteria. RESULTS: In diabetic subjects, median time to recovery from
      the first episode of MDD was 6.4 months; by 12 months from onset, 69% of the
      youths will have recovered. Within 2 years of recovery, 32% were at risk for a
      new episode; by 6.5 years, altogether 47% are estimated to have a recurrence.
      Only 37.5% of diabetic subjects received treatment for the first episode of
      depression, and 50% received treatment for the second episode. Overall rates of
      recovery and recurrence were indistinguishable in the diabetic and psychiatric
      control groups. However, young women with diabetes were at nine times greater
      risk for recurrent depression than their male counterparts, and diabetic subjects
      eventually spent more time being depressed than the control subjects.
      CONCLUSIONS: The course characteristics of MDD in young diabetic subjects and
      psychiatric control subjects appear to be similar in several regards. However,
      the eventual propensity of diabetic youths for more protracted depressions and
      the higher risk of recurrence among young diabetic women suggest that the mental
      health of patients with IDDM should be closely monitored. The findings confirm
      that depression is undertreated among patients in the primary health care sector.

PMID- 9028693
TI  - Motivational interviewing to improve adherence to a behavioral weight-control
      program for older obese women with NIDDM. A pilot study.
AB  - OBJECTIVE: The aim of this randomized pilot study was to examine whether the
      addition of motivational interviewing strategies to a behavioral obesity
      intervention enhances adherence and glucose control in older obese women with
      NIDDM. RESEARCH DESIGN AND METHODS: Twenty-two older obese women (41% black) with
      NIDDM were randomly assigned to 1) a standard 16-week group behavioral weight
      control program that provided instruction in diet, exercise, and behavioral
      modification or 2) the same group behavioral program with three individualized
      motivational interviewing sessions added. RESULTS: The motivational group
      attended significantly more group meetings (13.3 vs. 8.9), completed
      significantly more food diaries (15.2 vs. 10.1), and recorded blood glucose
      significantly more often (46.0 vs. 32.2 days) than the standard group. Further,
      participants in the motivational group had significantly better glucose control
      post-treatment (9.8 vs. 10.8%). Although both groups demonstrated significant
      weight loss, no differences were apparent between groups. CONCLUSIONS: These
      results suggest that augmenting a standard behavioral treatment program for obese
      women with NIDDM with a motivational interviewing component may significantly
      enhance adherence to program recommendations and glycemic control. Preliminary
      data warrant further investigation with larger samples and a longer follow-up.

PMID- 9028694
TI  - Chronic administration of levosulpiride and glycemic control in IDDM patients
      with gastroparesis.
AB  - OBJECTIVE: We evaluated the effect of chronic administration of levosulpiride, a
      prokinetic drug that is a selective antagonist for D2 dopamine receptors, on the
      glycemic control of IDDM subjects. RESEARCH DESIGN AND METHODS: The study was
      performed on 40 long-standing IDDM subjects with clinical signs of autonomic
      neuropathy and delayed gastric emptying. Gastric emptying time and glycemic
      parameters (diurnal glycemic profile and HbA1c) were checked under double-blind
      conditions before and after the administration of levosulpiride at the dosage of
      25 mg t.i.d. orally for 6 months, or placebo. RESULTS: No significant differences
      were noted in the glycemic and HbA1c values before and after 6 months of placebo
      administration. In contrast, after 6 months of levosulpiride, glycemic control
      had improved (HbA1c 6.7 +/- 0.4 and 5.7 +/- 0.3%, P < 0.01; mean daily glycemia
      10.9 +/- 0.8 and 8.8 +/- 0.4 mmol/l, P < 0.05, at the start and at the end of the
      study), while the dosage of injected insulin (0.65 +/- 0.02 IU.kg-1.day-1) and
      the number of severe hypoglycemic episodes remained unchanged. After 6 months of
      levosulpiride therapy, the time of gastric emptying was significantly reduced
      from 321 +/- 14 to 261 +/- 9 min (P < 0.001) and dyspeptic symptoms had improved.
      CONCLUSIONS: Our results show the importance of gastric emptying in the
      maintenance of glycemic control and the usefulness of chronic administration of
      levosulpiride in diabetic subjects with gastroparesis.

PMID- 9028695
TI  - Long-term therapy of IDDM with an implantable insulin pump. The Implantable
      Insulin Pump Trial Study Group.
AB  - OBJECTIVE: To examine the long-term benefits and risks of treatment of IDDM with
      an implantable programmable insulin pump. RESEARCH DESIGN AND METHODS: Seventy
      six patients with IDDM were studied at nine clinical centers. After 3-4 months of
      intensive subcutaneous therapy, the Infusaid Model 1000 pump was implanted, and
      insulin was delivered either intraperitoneally or intravenously for an average of
      39.6 +/- 10 months (251 patient-years). Data was collected for glycemic control,
      lipid levels, weight gain, insulin requirements, adverse events, and quality of
      life. Sixty-three patients were also followed for 8.5 +/- 6.3 months (45 patient
      years) after pump therapy was discontinued. RESULTS: Mean quarterly HbA1c fell
      with subcutaneous intensive therapy and remained stable on implantable pump
      therapy between 6.9 and 7.5%. Severe hypoglycemia was relatively rare, with only
      4 episodes/100 patient-years of implantable pump therapy. This rate was
      significantly less than with subcutaneous intensive therapy before implantable
      pump initiation (33 episodes/100 patient-years) or after discontinuation of
      implantable pump therapy (36/100 patient-years) (P < 0.003). Weight did not
      increase significantly in the 1st year of therapy, but increased by 2.0 +/- 4.3
      kg after 3 years of therapy. There were no significant differences in metabolic
      control or adverse events between intraperitoneal and intravenous insulin therapy
      except for minor differences in lipid levels and the more frequent development of
      catheter obstruction with intravenous delivery. Most pump slow-downs and catheter
      occlusions were corrected noninvasively. Quality of life, as measured by the
      Diabetes Control and Complications Trial instrument, showed high satisfaction and
      improved impact scores. CONCLUSIONS: Long-term implantable pump therapy
      maintained HbA1c in a range similar to intensive subcutaneous therapy, but with
      fewer episodes of severe hypoglycemia. Although pump and catheter occlusions
      remain a limitation, patient satisfaction with implantable pump therapy remains
      high.

PMID- 9028696
TI  - Self-monitoring of blood glucose in type I diabetic patients: comparison with
      continuous microdialysis measurements of glucose in subcutaneous adipose tissue
      during ordinary life conditions.
AB  - OBJECTIVE: To evaluate whether frequent self-monitoring of blood glucose (SMBG)
      sufficiently reflects the true diurnal glucose control during ordinary daily life
      in type I diabetic patients. RESEARCH DESIGN AND METHODS: By using a
      microdialysis technique, continuous monitoring of adipose tissue glucose was
      performed in 24 type I diabetic patients during ambulatory conditions. A
      microdialysis probe was implanted subcutaneously and perfused by a portable
      microinfusion pump. Dialysate fractions were collected in 1- to 2-h samples
      during 3 consecutive days. The diurnal microdialysis glucose profiles were
      compared with those obtained by SMBG recordings performed seven times a day.
      RESULTS: In seven patients, the SMBG profiles showed marked aberrations as
      compared to the continuous microdialysis glucose recordings; during the 3-day
      study period, 5-6 inconsistencies were registered. In only 4 patients (17%) did
      SMBG provide a valid reflection (0-2 inconsistencies) of the diurnal glucose
      profile, whereas in 13 patients the SMBG recordings paralleled the diurnal
      adipose tissue glucose profiles in an intermediate way (3-4 major
      inconsistencies). The inaccuracy of the SMBG data was due more often to the fact
      that wide glucose swings remained unrecognized, rather than to erroneous testing
      techniques (P < 0.05), and it was more evident during the night (P < 0.05).
      CONCLUSIONS: In many type I diabetic patients, the true diurnal variability in
      glycemia is too great to be accurately reflected even by frequent self-monitoring
      of blood glucose.

PMID- 9028697
TI  - Severe antibody-mediated human insulin resistance: successful treatment with the
      insulin analog lispro. A case report.
AB  - OBJECTIVE: To evaluate the efficacy of the insulin analog lispro (Lys B28, Pro
      B29) in severe insulin resistance caused by human insulin antibodies. CASE: A 27
      year-old man with a history of diabetes treated with human insulin for 3 years
      developed severe immunological insulin resistance caused by human insulin
      antibodies. Throughout follow-up (12 months) the insulin analog lispro was
      administered with an infusion pump as the only insulin therapy. The insulin dose
      decreased from an average of 300 U/day to 58 U/day, HbA1c decreased from 12.6 to
      7.4%, and human insulin antibodies decreased from 8,057 to 1,860 nU/ml.
      Hypoglycemic episodes during early morning disappeared. CONCLUSIONS: The insulin
      analog lispro might be suitable for the treatment of diabetic patients with
      substantially increased insulin antibody levels Apparently, the structural
      difference between the lispro and human insulin molecules prevented lispro from
      binding to the human insulin antibodies in this patient and consequently was
      nonimmunogenic.

PMID- 9028698
TI  - Circulating antibodies to common food antigens in Japanese children with IDDM.
AB  - OBJECTIVE: To investigate the humoral immune response to common food antigens in
      Japanese children with IDDM. RESEARCH DESIGN AND METHODS: IgG antibodies to cow's
      milk, beta-lactoglobulin, bovine serum albumin (BSA), alpha-lactalbumin, and hens
      egg ovalbumin were examined by enzyme-linked immunosorbent assay in the sera of
      33 patients with IDDM, ages 11.8 +/- 3.4 years. The data were compared with that
      of 50 normal subjects, ages 10.3 +/- 5.1 years, who acted as control subjects. A
      positive antibody to a food antigen was defined as an antibody titer greater than
      the 95th percentile value in normal subjects. RESULTS: Children with IDDM had
      significantly higher median titers of IgG antibodies to beta-lactoglobulin and
      ovalbumin (P = 0.03 and P = 0.0005 respectively). More children with IDDM than
      control subjects had positive IgG antibody to ovalbumin (21 vs. 6%, P = 0.04).
      Titers, as well as the number of positive antibodies to other food antigens,
      including BSA, did not differ between the two groups. CONCLUSIONS: Japanese
      children with IDDM show an enhanced humoral immune response to beta-lactoglobulin
      and ovalbumin, a phenomenon that may be related to the pathogenesis of the
      disease.

PMID- 9028699
TI  - The effect of prepubertal diabetes duration on diabetes. Microvascular
      complications in early and late adolescence.
AB  - OBJECTIVE: To define the significance of prepubertal diabetes duration in the
      development of diabetic microvascular complications in adolescents. RESEARCH
      DESIGN AND METHODS: Study A compares complications in 38 prepubertal (PreP) and
      140 pubertal (Pub) subjects of the same age (10-14 years) and diabetes duration
      (3-12 years) to determine if the absence of puberty itself confers a lower risk
      of complications. Study B examines the importance of prepubertal and pubertal
      diabetes duration in 193 older adolescents (ages 15-22 years) with prepubertal
      onset of diabetes. Retinopathy status was assessed using stereoscopic fundus
      photography of seven fields per eye. Albumin excretion rate (AER) was assessed by
      three consecutive overnight urine collections, using a polyclonal
      radioimmunoassay. RESULTS: In study A, there were no significant differences
      between the PreP and Pub groups for retinopathy (27 vs. 29%, P = 0.8) or
      differences in elevated AER (17 vs. 31%, P = 0.1). In study B, longer prepubertal
      diabetes duration improved the prediction for retinopathy over postpubertal
      duration alone (P < 0.0005). No relationship with duration was found for elevated
      AER (> 7.5, > 15, and > 30 micrograms/min). CONCLUSIONS: Prepubertal subjects
      with diabetes did not have less retinopathy or elevated albumin excretion
      compared with pubertal subjects of the same age. Prepubertal diabetes duration is
      significantly related to the presence of retinopathy in adolescents.

PMID- 9028700
TI  - Low prevalence of islet autoantibodies in patients with gestational diabetes
      mellitus.
AB  - OBJECTIVE: To determine the proportion of patients with gestational diabetes
      mellitus (GDM) who have serological characteristics typical of IDDM. RESEARCH
      DESIGN AND METHODS: Islet cell antibodies (ICAs), insulin autoantibodies (IAAs),
      GAD65, and IA-2 antibodies were measured in 145 pregnant women with GDM, 33 with
      impaired glucose tolerance (IGT), and in 73 with normal glucose tolerance (NGT).
      ICAs were measured by indirect immunofluorescence; GAD65 and IA-2 antibodies, by
      a radio-ligand immunoassay incorporating 35S-labeled recombinant antigen; and
      IAAs, by a liquid-phase radiobinding assay. RESULTS: The prevalences of islet
      autoantibodies were low and not significantly different between groups. ICAs were
      detected at levels ranging from 5 to 45 Juvenile Diabetes Foundation U in 14
      (10%) women with GDM, 2 (6%) women with (GT, and in 4 (5%) women with NGT. IAAs
      were detected at levels between 3 and 4 SD above the mean in 4 (3%) women with
      GDM, 0 women with IGT, and in 1 (1%) woman with NGT. None had both ICAs and IAAs.
      Neither GAD65 nor IA-2 antibodies, which have been detected in the majority of
      pre-IDDM and IDDM patients, were found in NGT, IGT, or GDM patients. CONCLUSIONS:
      Low-titer ICAs and IAAs are not infrequent in pregnant women, but multiple islet
      autoantibodies and antibodies to GAD65 or IA-2 were not found in GDM. These
      findings suggest that the serological characteristics of IDDM are rare in GDM.

PMID- 9028701
TI  - Increased urinary albumin and retinol-binding protein in type I diabetes. A study
      of identical twins.
AB  - OBJECTIVE: Indexes of early renal glomerular and tubular dysfunction have been
      demonstrated in type I diabetes, but it remains uncertain whether such changes
      are genetically determined or are secondary to the disease process. We therefore
      undertook to study whether early markers of renal dysfunction are a consequence
      of type I diabetes or inherited. RESEARCH DESIGN AND METHODS: We estimated both
      urinary albumin excretion (UAE) and urinary retinol-binding protein (RBP) in 51
      identical twin pairs discordant for type I diabetes and in 51 matched control
      subjects. RESULTS: UAE and RBP were significantly higher in the diabetic twins
      than in their nondiabetic co-twins (P < 0.0001 and P < 0.0002, respectively).
      Seven diabetic twins had elevated UAE, but none of the nondiabetic co-twins did.
      In a subgroup of 44 twins with normal UAE (albumin excretion rate < 20
      micrograms/min), diabetic twins had both a higher albumin excretion function
      (median [range]; 0.64 [0.18-2.74] mg/mmol creatinine) than their nondiabetic co
      twins (0.48 [0.24-1.40], P < 0.01) and higher levels of RBP excretion (10.4 [4.0
      167.0] micrograms/mmol creatinine) than their nondiabetic co-twins (7.5 [0.97
      23.0], P < 0.05). Values between twins of a pair were significantly correlated
      for RBP (r = 0.36, P < 0.05) but not for UAE (r = 0.13). CONCLUSIONS: These
      results suggest that in type I diabetes, an index of renal tubular function
      (RBP), but not glomerular function (UAE), is influenced by shared genetic and
      nongenetic factors. Type I diabetes can affect renal tubular function even when
      glomerular function is normal. We conclude that neither the increased UAE nor
      urinary RBP found in type I diabetes is inherited independently of the diabetes
      process.

PMID- 9028702
TI  - Cholesterol absorption, synthesis, and LDL metabolism in NIDDM.
AB  - OBJECTIVE: Cholesterol and lipoprotein metabolism was studied in mildly
      hypercholesterolemic nonobese men with NIDDM to find out which metabolic
      parameters regulate serum cholesterol level in these NIDDM subjects. RESEARCH
      DESIGN AND METHODS: Nonobese NIDDM subjects (n = 13) and control subjects (n =
      18) with serum cholesterol > or = 6.0 and triglycerides < or = 2.5 mmol/l were
      studied on a similar monoene-enriched diet. Cholesterol absorption was studied
      with peroral double isotopes and by measuring serum plant sterols with gas-liquid
      chromatography; cholesterol synthesis was studied by measuring sterol balance and
      by measuring serum cholesterol precursor sterols; and LDL kinetics was measured
      with 131I-labeled autologous apoprotein (apo) B. RESULTS: Cholesterol absorption
      was significantly lower in NIDDM subjects than in the control subjects, as
      detected by low serum plant sterol levels and absorption percentage (23 vs. 29%,
      P < 0.05). Cholesterol synthesis was significantly higher in NIDDM subjects than
      in the control subjects, as detected by precursor sterols or balance data (18 vs.
      12 mg.kg-1.day-1, P < 0.01), cholesterol turnover (19 vs. 13 mg.kg-1.day-1, P <
      0.01), and LDL apo B removal (0.343 vs. 0.267 pools/day, P < 0.01). Serum total
      and LDL cholesterol levels were inversely correlated with cholesterol synthesis,
      which was positively related to the catabolism of LDL apo B and negatively
      related to cholesterol absorption efficiency. CONCLUSIONS: In this small selected
      group of mildly hypercholesterolemic nonobese NIDDM subjects, the regulation of
      serum cholesterol levels was achieved by the homeostasis between cholesterol
      absorption, synthesis, and LDL fractional catabolism. Cholesterol turnover and
      removal of LDL apo B were high in NIDDM subjects, compared with the control
      subjects, whereas cholesterol absorption efficiency was abnormally low Because of
      the relatively small number of selected subjects, the present results are not
      directly applicable to the overall NIDDM population.

PMID- 9028703
TI  - Translation of the diabetes nutrition recommendations for health care
      institutions.

PMID- 9028704
TI  - Translation of the diabetes nutrition recommendations for health care
      institutions. American Diabetes Association.

PMID- 9028705
TI  - A brave new world for nutrition and diabetes.

PMID- 9028706
TI  - American Diabetes Association annual meeting 1996: complications, treatment of
      type I diabetes, and IGF-I.

PMID- 9028707
TI  - Lipoprotein(a) and retinopathy in IDDM and NIDDM patients.

PMID- 9028708
TI  - Is rapid gastric emptying in type II diabetic patients emptying the stomach in
      less time than in normal subjects?

PMID- 9028709
TI  - Comment on study by Gentzkow et al.

PMID- 9028710
TI  - American Diabetes Association: clinical practice recommendations 1997.

PMID- 9028711
TI  - Glucose and alpha-ketoisocaproate induce transient inward currents in rat
      pancreatic beta cells.
AB  - The perforated patch technique was used to study changes in membrane potential
      and whole-cell currents in single isolated rat pancreatic beta-cells during
      stimulation with glucose or alpha-ketoisocaproate. Increasing the glucose
      concentration from 4 to 20 mmol/l, or addition of 15 mmol/l alpha
      ketoisocaproate, caused depolarization and, in most cases, initiation of action
      potentials. Under voltage-clamp conditions close to a potassium equilibrium
      potential (EK) (-60 to -70 mV) these effects were accompanied by the appearance
      of transient inward currents. These transient currents resembled those elicited
      during cell swelling in response to a 10% hypotonic bath solution, a manoeuvre
      which also caused beta-cell depolarization and electrical activity. Tolbutamide
      (0.2 mmol/l), in the absence of glucose depolarized beta-cells but did not induce
      transient inward currents. Nutrient-induced electrical activity and inward
      currents were abolished by the anion channel inhibitors 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid and 5-nitro-2-(3
      phenylpropylamino) benzoic acid, compounds which also inhibited glucose-induced
      insulin release. It is concluded that nutrient secretagogues induce transient
      inward currents in isolated rat beta-cells, possibly by activating a volume
      sensitive anion conductance. These inward currents could enhance the intensity of
      electrical, and hence secretory, activity in the beta-cell during nutrient
      stimulation.

PMID- 9028712
TI  - Teratogenic effect of diabetic serum is prevented by supplementation of
      superoxide dismutase and N-acetylcysteine in rat embryo culture.
AB  - Congenital malformations are more common in offspring of diabetic mothers than
      offspring of non-diabetic mothers. The precise cell biological mechanism leading
      to the increased incidence of congenital malformations in diabetic pregnancy is
      not known. In previous studies increased glucose and beta-hydroxybutyrate
      concentrations were found to cause embryonic dysmorphogenesis. We have previously
      shown that rat embryos, cultured in serum from insulin-treated diabetic rats,
      develop malformations, despite normalisation of glucose and beta-hydroxybutyrate
      concentration, thereby suggesting a multifactorial teratological nature of the
      diabetic environment. In the present study, therefore, we aimed to characterise
      the teratogenic activity of various components of diabetic serum and in addition
      to study the possible anti-teratogenic effects of supplementation of superoxide
      dismutase and N-acetylcysteine in rat embryo culture. We found that diabetic
      serum has a teratogenic effect on embryo development, a capacity residing in the
      alteration of several serum components in addition to glucose. Improving the
      embryonic capability to scavenge oxygen radicals, either by increasing superoxide
      dismutase activity or by supplying a rate-limiting precursor (N-acetylcysteine)
      for the enhanced synthesis of reduced glutathione, blocks the embryonic
      dysmorphogenesis.

PMID- 9028713
TI  - Alterations in the expression of the alpha 3 beta 1 integrin in certain membrane
      domains of the glomerular epithelial cells (podocytes) in diabetes mellitus.
AB  - In view of the major alterations which take place at the level of the
      extracellular matrix of the glomerular wall in diabetes mellitus and the key
      roles played by beta 1 integrins in cell-to-matrix interactions, it is imperative
      to understand the role played by integrins in the development of diabetic
      glomerulosclerosis. In the present study, we revealed by immunocytochemistry the
      ultrastructural distribution of the alpha 3 beta 1 at the level of the plasma
      membrane of the different renal glomerular cells from short- and long-term
      diabetic rats. For the endothelial cells, the labelling present on both the
      luminal and abluminal plasma membranes was low. For the podocyte epithelial
      cells, the labelling was present on both the luminal and basal plasma membranes,
      the former being concentrated at points of contact between podocyte foot
      processes. The labelling on the basal plasma membrane was more significant and
      similar in domains facing either the glomerular basement membrane or the
      mesangial matrix. The plasma membrane of mesangial cells also exhibited alpha 3
      beta 1. The labelling was recorded under diabetic conditions, at the same sites,
      with similar intensities, alongside that of the basal plasma membrane of
      podocytes facing the glomerular basement membrane, the density of which decreased
      significantly. This decrease in labelling was similar in renal tissues from short
      and long-term diabetic animals. These results demonstrate that alpha 3 beta 1
      present at the podocyte basal plasma membrane facing the glomerular basement
      membrane, which undergoes important alterations in diabetes, could be involved in
      the major dysfunctions of the glomerular wall characteristic of diabetic
      glomerulosclerosis. Since the changes in integrin were found to occur as early as
      after 1 month of hyperglycaemia, when morphological alterations of the glomerular
      basement membrane are not yet established, we propose that they constitute an
      early event which precedes the onset of diabetic nephropathy.

PMID- 9028714
TI  - Renal antioxidant enzyme mRNA levels are increased in rats with experimental
      diabetes mellitus.
AB  - Exposure to high glucose concentrations increases the mRNA levels of oxygen
      radical scavenging enzymes in cultured endothelial cells, suggesting a
      compensatory response to increased free radical production. To test the
      hypothesis that this response also occurs in vivo, Cu.Zn-superoxide dismutase
      (Cu.Zn-SOD) and catalase mRNA levels, were measured in the kidneys of Sprague
      Dawley rats 17 days after intravenous injection of streptozotocin (60 mg/kg body
      weight) and compared with those of control rats. Diabetic rats were either left
      untreated or given differing insulin regimens (2. 3-8, 6-10 IU/day) in two
      different experiments that were designed to achieve varying degrees of metabolic
      control. Cu,Zn-SOD and catalase mRNA levels were measured by Northern blot
      hybridization and standardized by 28S ribosomal RNA determination. Renal Cu,Zn
      SOD and catalase mRNA levels were significantly greater in untreated diabetic and
      in low-dose (2 IU/day) insulin-treated rats than in controls. Treatment with a
      moderate dose (3-8 IU/day) of insulin normalized catalase but not Cu,Zn-SOD mRNA
      levels. The highest insulin regimen (6-10 IU/day), in addition to achieving
      complete metabolic control as evidenced by normal growth and plasma glucose
      levels, normalized both catalase and Cu,Zn-SOD mRNA levels. Thus, in rats with
      streptozotocin-induced diabetes Cu,Zn-SOD and catalase renal mRNA levels are
      greater than in normal rats. This difference is prevented by sufficient insulin
      dosage to normalize plasma glucose and might be due to an increased production of
      free radicals.

PMID- 9028715
TI  - Substrate autoregulation of glucose transport: hexose 6-phosphate mediates the
      cellular distribution of glucose transporters.
AB  - Exposure of rat skeletal muscle and skeletal muscle cell lines to high glucose
      levels results in a time- and dose-dependent reduction of the rate of hexose
      uptake, paralleled by a reduction in the plasma membrane density of glucose
      transporters. The mechanism of this process was investigated in cultured L8
      myocytes. Low concentrations (0.5-2.0 mmol/l) of deoxyglucose mimicked the
      downregulatory action of 20 mmol/l glucose both regarding the time-course and
      magnitude of the effect, but in an irreversible manner. A dose-dependent
      relationship between intracellular accumulation of deoxyglucose 6-phosphate and
      the magnitude of the downregulatory response was observed. Depletion of
      intracellular deoxyglucose 6-phosphate restored the rate of hexose transport to
      the control level. The reduction of hexose transport activity by deoxyglucose
      occurred independently of ATP depletion which by itself produced the opposite
      effect. The effects of deoxyglucose and high glucose on hexose transport were
      associated with reduced transport maximal velocity and GLUT1 transporter
      abundance in the plasma membranes of myocytes, as assessed by cell surface
      biotinylation. The reduction of myocyte GLUT1 mRNA content, observed after
      exposure to high glucose, did not accompany the transport down regulatory action
      of deoxyglucose. We suggest that hexose 6-phosphate is the mediator of the
      downregulatory signal for subcellular redistribution of GLUT1 in L8 myocytes. The
      signal responsible for reducing the GLUT1 mRNA level may be related to glucose
      metabolites downstream of the hexokinase reaction.

PMID- 9028716
TI  - Effect of 1,25-dihydroxycholecalciferol on glucose metabolism in gestational
      diabetes mellitus.
AB  - The effect of 1,25-dihydroxyvitamin D supplement on glucose metabolism was
      evaluated in 12 women with gestational diabetes mellitus (GDM). All women had an
      oral glucose tolerance test (OGTT) performed at inclusion in the study.
      Thereafter, each patient was instructed to continue their normal diet during the
      following 2 days, after which they received 2 micrograms/m2 Etalpha i.v. 2 h
      prior to the second OGTT. During the next 14 days each patient received 0.25
      microgram Etalpha orally, after which a third OGTT was performed. On average the
      level of 1,25-dihydroxyvitamin D3 at inclusion at baseline significantly
      increased after i.v. 1,25-dihydroxyvitamin D3 (from 92 to 138 ng/l [p < 0.001]),
      but returned to the baseline level after 2 weeks of oral Etalpha (85 ng/l).
      Simultaneously, the glucose level decreased from 5.6 to 4.8 mmol/l (p < 0.01)
      after i.v. treatment with 1,25-dihydroxyvitamin D3, but did not differ
      significantly from inclusion following 2 weeks of oral Etalpha. There was no
      difference between the glucose concentrations during OGTT prior to and after i.v.
      or oral 1,25-dihydroxyvitamin D3, in contrast to the insulin levels which tended
      to be lower after both i.v. and oral supplementation. In a multiple regression
      model including 1,25-dihydroxyvitamin D3, insulin, weight and height against
      glucose, only 1,25-dihydroxyvitamin D3 and insulin were selected for the final
      model (r2 = 0.73, p < 0.0001). Our results suggest that supplements of 1,25
      dihydroxyvitamin D3 influence glucose metabolism in patients with GDM probably by
      increasing the insulin sensitivity.

PMID- 9028717
TI  - Effect of omega 3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty
      acid content in NIDDM patients.
AB  - This study was conducted to examine the effect of omega 3 fatty acid
      supplementation on plasma lipid, cholesterol and lipoprotein fatty acid content
      of non-insulin-dependent diabetic individuals consuming a higher (0.65, n = 10)
      or lower (0.44, n = 18) ratio of dietary polyunsaturated to saturated fatty acid
      (P/S). The participants were initially given an olive oil supplement (placebo)
      equivalent to 35 mg of 18:1. kg body weight-1.day-1 for 3 months. This was
      followed by two omega 3 supplement periods in a randomized crossover. In these 3
      month periods, participants were given a linseed oil supplement equivalent to 35
      mg of 18:3 omega 3.kg body weight-1.day-1 or a fish oil supplement equivalent to
      35 mg of 20:5 omega 3 + 22:6 omega 3.kg body weight-1. day-1. At the end of each
      supplement period, a blood sample was drawn from each participant for lipid,
      lipoprotein, insulin, glucagon and C-peptide analyses. At the end of each 3-month
      period a 7-day dietary record was completed to calculate dietary fat intake and
      P/S ratio. Results indicate that fish oil significantly reduced plasma
      triacylglycerol level (p < 0.05) and increased 20:5 omega 3 and 22:6 omega 3
      content of all lipoprotein lipid classes. Linolenic acid supplementation had no
      effect on plasma triacylglycerol level, but it increased 18:3 omega 3 content of
      lipoprotein cholesterol ester fractions (p < 0.05). A slight increase in 20:5
      omega 3, but not 22:6 omega 3, content was noted in lipoprotein lipid classes as
      a result of 18:3 omega 3 supplementation. LDL and HDL cholesterol, insulin,
      glucagon and C-peptide levels were not affected by either omega 3 supplement. It
      is concluded that a modest intake of omega 3 fatty acids, such as could be
      obtained from consuming fish regularly, will reduce plasma triglyceride level
      without affecting LDL or HDL cholesterol levels.

PMID- 9028718
TI  - A search for evidence of viral infection in pancreases of newly diagnosed
      patients with IDDM.
AB  - Techniques were developed to look for evidence of viral infection in formalin
      fixed paraffin-embedded autopsy pancreatic tissues from patients who had died of
      recent-onset insulin-dependent diabetes mellitus. DNA extracted from 47
      pancreases in which good DNA preservation was confirmed was analysed by a
      polymerase chain reaction for Epstein-Barr virus and by a nested polymerase chain
      reaction for cytomegalovirus. Histological sections from 29 pancreases in which
      there was good RNA preservation were tested for the presence of enterovirus and
      Epstein-Barr virus using in situ hybridization techniques. Seventy-five
      pancreases were analysed immunohistochemically for the presence of mumps virus.
      None of these viruses could be detected in any of the diabetic pancreases
      studied. Control studies suggested that the techniques employed were as sensitive
      as culture done at the time of autopsy. Pancreas was available for study in 9
      infants who had died of myocarditis; enterovirus was demonstrable in islets in 5
      of these cases. An acute or persisting infection in the pancreas at the time of
      clinical onset of insulin-dependent diabetes by any of the 4 virus included in
      this study seems unlikely.

PMID- 9028719
TI  - Are risk factors for conversion to NIDDM similar in high and low risk
      populations?
AB  - Mexican Americans have an increased risk of non-insulin-dependent diabetes
      mellitus (NIDDM) relative to non-Hispanic whites which is only partially
      explained by their excess overall obesity and unfavourable body fat distribution.
      Non-diabetic Mexican Americans have hyperinsulinaemia and insulin resistance
      relative to non-Hispanic whites. We therefore hypothesized that the insulin
      resistance might be a more important predictor of NIDDM in high-risk populations
      characterized by obesity and insulin resistance, while compromised insulin
      secretion might be a more important risk factor for NIDDM in low-risk
      populations. We assessed the ability of ethnicity (Mexican American vs non
      Hispanic white), age, overall adiposity (body mass index [BMI]), unfavourable
      body fat distribution (as assessed by waist-to-hip ratio [WHR]), glucose
      tolerance (impaired glucose tolerance vs normal glucose tolerance), fasting
      insulin and compromised insulin secretion (as assessed by increment in insulin to
      the increment in glucose over the first 30 min of an oral glucose tolerance test
      (delta I30/delta G30)) to predict future NIDDM. In the 8-year follow-up of the
      San Antonio Heart Study, NIDDM developed in 11.7% (107/914) of Mexican Americans
      and in 5.0% (18/362) of non-Hispanic whites (p < 0.001). Multivariate predictors
      of NIDDM by multiple logistic regression analysis included increased age, BMI,
      WHR, fasting insulin and impaired glucose tolerance and decreased insulin
      secretion. The strongest independent predictors of NIDDM were high fasting
      insulin and decreased insulin secretion. These risk factors predicted NIDDM
      equally well in high and low-risk populations.

PMID- 9028720
TI  - Influence of protamine on adhesion, chemotaxis and proliferation of human
      vascular smooth muscle cells.
AB  - It has been shown that, in streptozotocin diabetic rats, protamine-retarded
      insulin administered in vivo stimulates intimal hyperplasia in balloon-injured
      carotid artery. The aim of this study was to evaluate the influence of protamine
      on cultured human vascular smooth muscle cells (h VSMC), by observing its effects
      on adhesion, chemotaxis and proliferation. hVSMC were isolated during abdominal
      surgery, cultured and utilized at passages 6-10. We observed that protamine
      stimulates: 1) cell adhesion in the concentration range 0.04-20 micrograms/ml
      (analysis of variance, ANOVA, p < 0.0001); 2) cell chemotaxis in the absence of
      fetal calf serum (FCS) in the concentration range 1-200 micrograms/ml (ANOVA, p <
      0.0001) and in the presence of 1% FCS in the concentration range 5-200
      micrograms/ml (ANOVA, p < 0.0001), further enhancing the chemotaxis induced by
      10% FCS in the concentration range 20-200 micrograms/ml (ANOVA, p < 0.0001); 3)
      cell proliferation and 3H-thymidine incorporation from 1 to 5 micrograms/ml
      (ANOVA, p < 0.0001); 4) cell c-fos oncoprotein nuclear expression. We also
      observed that protamine effects on chemotaxis, proliferation and c-fos expression
      are inhibited by heparin that human insulin stimulates cell proliferation and 3H
      thymidine incorporation (ANOVA, p < 0.0001) at concentrations equal to or greater
      than 480 pmol/l and that these effects of insulin persist in the presence of
      protamine. In conclusion, protamine influences hVSMC behaviour by interfering
      with biological functions involved in atherogenesis. The concentrations used in
      this short-term in vitro study were higher than those probably occurring in vivo
      in patients chronically treated by protamine-retarded insulin preparations:
      further studies, therefore, are needed to evaluate the safety of protamine as a
      retardant of insulin action in vivo.

PMID- 9028722
TI  - Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men
      with IDDM.
AB  - Pramlintide, a human amylin analogue, reduces hyperglycaemia after meals in
      patients with insulin-dependent diabetes mellitus (IDDM). We investigated whether
      this was due to delayed gastric emptying. Eight men with uncomplicated IDDM were
      studied twice in a randomised, double-blind crossover design. Euglycaemia was
      maintained overnight by intravenous infusion of glucose and/or insulin and the
      following morning a 5-h infusion of pramlintide 25 micrograms/h or placebo was
      started at 08.00 hours. At 08.30 hours the patients injected their normal morning
      insulin dose subcutaneously and 30 min later ate a meal (600 kcal, 50%
      carbohydrate) of which the solid component was labelled with Technetium-99 m and
      the liquid with Indium-111 to quantify gastric emptying. Gamma-scintigraphic
      images were obtained every 20 min for the next 4 h. Insulin and glucose were
      infused as necessary to maintain blood glucose levels within 3 mmol/l of the pre
      meal value. Compared to placebo, pramlintide significantly delayed emptying of
      both liquid (median lag time 69 vs 7.5 min) and solid (median lag time 150 vs
      44.5 min) components of the meal. Pramlintide delayed gastric emptying so much
      that t50 values could not be calculated for solid or liquid. Amylin agonists such
      as pramlintide may, therefore, be of value in improving glycaemic control in IDDM
      by modifying gastric emptying.

PMID- 9028721
TI  - UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate
      amidotransferase activities in insulin-sensitive tissues.
AB  - Glutamine:fructose 6-phosphate amidotransferase (GFA) is rate-limiting for
      hexosamine biosynthesis, while a UDP-GlcNAc beta-N-acetylglucosaminyltransferase
      (O-GlcNAc transferase) catalyses final O-linked attachment of GlcNAc to serine
      and threonine residues on intracellular proteins. Increased activity of the
      hexosamine pathway is a putative mediator of glucose-induced insulin resistance
      but the mechanisms are unclear. We determined whether O-GlcNAc transferase is
      found in insulin-sensitive tissues and compared its activity to that of GFA in
      rat tissues. We also determined whether non-insulin-dependent diabetes mellitus
      (NIDDM) or acute hyperinsulinaemia alters O-GlcNAc transferase activity in human
      skeletal muscle. O-GlcNAc transferase was measured using 3H-UDP-GlcNAc and a
      synthetic cationic peptide substrate containing serine and threonine residues,
      and GFA was determined by measuring a fluorescent derivative of GlcN6P by HPLC. O
      GlcNAc transferase activities were 2-4 fold higher in skeletal muscles and the
      heart than in the liver, which had the lowest activity, while GFA activity was 14
      36-fold higher in submandibular gland and 5-18 fold higher in the liver than in
      skeletal muscles or the heart. In patients with NIDDM (n = 11), basal O-GlcNAc
      transferase in skeletal muscle averaged 3.8 +/- 0.3 nmol/mg.min, which was not
      different from that in normal subjects (3.3 +/- 0.4 nmol/mg.min). A 180-min
      intravenous insulin infusion (40 mU/m2.min) did not change muscle O-GlcNAc
      transferase activity in either group. We conclude that O-GlcNAc transferase is
      widely distributed in insulin-sensitive tissues in the rat and is also found in
      human skeletal muscle. These findings suggest the possibility that O-linked
      glycosylation of intracellular proteins is involved in mediating glucose
      toxicity. O-GlcNAc transferase does not, however, appear to be regulated by
      either NIDDM or acute hyperinsulinaemia, suggesting that mass action effects
      determine the extent of O-linked glycosylation under hyperglycaemic conditions.

PMID- 9028723
TI  - Physiological and genetic characterization of the Gly40Ser mutation in the
      glucagon receptor gene in the Sardinian population. The Sardinian Diabetes
      Genetic Study Group.
AB  - A Gly40Ser amino acid substitution in the glucagon receptor gene has been
      associated with non-insulin-dependent diabetes mellitus (NIDDM), but the
      questions raised about its physiological implications have not been resolved. The
      aim of this study was to determine the frequency of the Gly40Ser mutation in
      different regions of Sardinia and to investigate the physiological implications
      of the mutation in glucose and insulin homeostasis. We studied a population of
      691 subjects selected on the basis of their Sardinian origin. Only heterozygous
      subjects were found, 21 of 574 (3.6%) in NIDDM patients and 5 of 117 in non
      diabetic subjects (4.2%). In northern Sardinia 3.4% of the NIDDM patients were
      carriers of the Gly40Ser substitution, 1.4% in central Sardinia, while 7.6%
      carried the substitution in the Southern part. No significant differences were
      found between hypertensive and normotensive subjects with respect to the presence
      of Gly40Ser. Ten subjects with Gly40Ser were carefully matched for diabetic
      state, BMI, age, sex, and geographical origin with 10 patients with Gly40, and a
      glucagon infusion test was performed using 1, 3, 9 and 27 ng glucagon kg-1.min-1
      for 30 min. Blood for determination of glucose, glucagon, and insulin
      concentrations was drawn at 15-min intervals from the Controlateral arm. Plasma
      glucagon increased dose-dependently during the infusion with no significant
      difference between the two groups. Carriers of Gly40Ser had a significantly lower
      (p < 0.02) increase in plasma glucose concentration in response to glucagon
      infusion compared to Gly40 homozygous subjects at all times, while the plasma
      insulin increase was not significantly different at any time. In conclusion, our
      results indicate that the Gly40Ser variation is not associated with NIDDM in the
      Sardinian population and that its frequency varies in different parts of
      Sardinia. Moreover in vivo Gly40Ser plays a physiological role in the glucose
      homeostasis under glucagon control both in NIDDM and non-diabetic subjects. This
      latter result suggests that this amino acid substitution in the glucagon receptor
      may lead to a decreased blood glucose concentration because of the reduced
      stimulation of liver glucose output via the glucagon receptor.

PMID- 9028724
TI  - IA-2-autoantibodies complement GAD65-autoantibodies in new-onset IDDM patients
      and help predict impending diabetes in their siblings. The Belgian Diabetes
      Registry.
AB  - IA-2 has been identified as an autoantigen that is recognized by immunoglobulins
      from insulin-dependent diabetic (IDDM) patients. Using a liquid phase
      radiobinding assay, we performed an IA-2-autoantibody (IA-2-Ab) assay in 474 IDDM
      patients and 482 non-diabetic control subjects aged 0-3 years. IA-2-Ab were
      detected in 58% of the patients and 0.8% of control subjects. Their prevalence in
      patients was lower than that of islet cell autoantibodies (ICA; 73%) or glutamic
      acid decarboxylase (M(r) 65 kDa)-autoantibodies (GAD65-Ab; 82%) but higher than
      that of insulin autoantibodies (IAA; 42%). IA-2-Ab were more frequent in patients
      under age 20 years (70%) than between 20 and 40 years (45%; p < 0.001). In the
      whole IDDM group, 92% of patients were positive for at least one of the three
      molecular assays, which is higher than the positivity for the ICA assay (73%).
      Only 1% was negative in the molecular assays and positive in the ICA assay. IA-2
      Ab levels were positively correlated with ICA titres (p < 0.001) and HLA DQ
      A1*0301-DQ B1*0.02 (p < 0.003) by multivariate analysis. In a group of 481 non
      diabetic siblings (age 0-39 years) of IDDM patients only 7 were IA-2-Ab positive
      (1.5%). All seven were under age 20 years and positive for at least two other
      autoantibodies and for DQ A1*0301-DQB1*0302. Four of these seven developed IDDM
      during the 6-70-month follow-up period. The positive predictive value of IA-2-Ab
      (57%) was higher than that of ICA, GAD65-Ab or IAA alone, or in combination (< or
      = 20%) but these calculations are restricted by the relatively short observation
      period and the small number of cases. The only IA-2-Ab-negative case of pre
      diabetes was also negative for IAA and GAD65-Ab, while it was strongly positive
      for ICA. In conclusion, IA-2-Ab show a high diagnostic specificity for IDDM and
      are predictive markers of impending diabetes in siblings of patients. In
      combination with other molecular antibody assays they may replace ICA testing in
      future. Our data also indicate that other autoantibodies than IA-2-Ab, GAD65-Ab
      and IAA contribute to ICA.

PMID- 9028725
TI  - Elevated plasma endothelin-1 levels as an additional risk factor in non-obese
      essential hypertensive patients with metabolic abnormalities.
AB  - Circulating endothelin-1 concentration was evaluated in 93 lean patients with
      essential hypertension, of whom 16 had impaired glucose tolerance and
      hyperlipidaemia, 25 had impaired glucose tolerance, 28 had hyperlipidaemia and 24
      had no metabolic abnormalities; we also studied 22 control subjects. All groups
      were age- and sex-matched. Plasma endothelin-1 levels were higher (p < 0.05) in
      hypertensive patients with impaired glucose tolerance and hyperlipidaemia than in
      the remaining groups and were directly correlated with fasting insulin levels (r
      = 0.506, p = 0.045). Therefore, circulating endothelin-1 concentrations are
      elevated in hypertensive patients with a high-risk profile due to the presence of
      metabolic abnormalities, and might favour the development of vascular damage.

PMID- 9028726
TI  - Is GLUT2 required for glucose sensing?

PMID- 9028727
TI  - Are there kinetic advantages of GLUT2 in pancreatic glucose sensing?

PMID- 9028728
TI  - Islet cell autoantigen 69 kDa (ICA69) is preferentially expressed in the human
      islets of Langerhans than exocrine pancreas.

PMID- 9028729
TI  - Beta 3-adrenergic receptor gene polymorphisms and determination of adiposity and
      fat distribution in normal female twins.

PMID- 9028730
TI  - Beta 3-adrenergic receptor gene variant and lipid metabolism in Pima Indians.

PMID- 9028731
TI  - A simplified polymerase chain reaction assay for detection of chromosomal
      translocations in hematologic malignancies.
AB  - The polymerase chain reaction (PCR) is a rapid and highly sensitive method for
      detection of a variety of chromosomal translocations in malignant tissues.
      Detection of each different type of translocation, or even DNA rearrangements at
      different breakpoint cluster regions within the same type of translocation,
      usually requires separate thermocycling parameters and/or buffer conditions. In
      this report, we describe a single set of reaction conditions, making use of
      progressively decreasing annealing temperatures and a standardized reaction
      buffer, that permits the detection of several different translocations
      simultaneously. Specificity equal to or better than current procedures and
      sensitivity equivalent to one malignant cell in 1 x 10(5) normal cells was
      achieved for translocations t(14;18)(q32;q21), t(9;22)(q34;q11), and
      t(4;11)(q21;q23). For PCRs formerly requiring different, fixed annealing
      temperatures, the new technology allows batching or multiplexing of PCR samples.
      Thus, shorter turnaround time, decreased cost per sample, and simplified
      mechanization of PCR may be attainable using this assay.

PMID- 9028732
TI  - Activation of TRK genes in Ewing's sarcoma. Trk A receptor expression linked to
      neural differentiation.
AB  - Trk receptors have been identified by immunohistochemical methods in primitive
      neuroectodermal tumor (PNET)/Ewing's sarcoma (ES). However, the presence of
      different members of the Trk family of receptors in PNET/ES has not been
      specified. We have examined whether Trk A, B, and C receptors are specifically
      expressed in ES both with and without features of neural differentiation. Ten ES
      tumors (five primary tumors of bone and five extraosseous tumors transplanted
      into nude mice) were investigated for expression of Trk receptors by
      immunohistochemistry and reverse transcription-polymerase chain reaction. One
      primary ES and the five grafted ES tumors exhibited signs of neural
      differentiation; the remaining four primaries were undifferentiated ES. Other
      tumor types were analyzed as controls; they included three neuroblastomas (NB),
      two lymphomas, and single cases of pheochromocytoma (PHEO), schwannoma (SCHW),
      osteosarcoma, and carcinoma of breast, colon, and kidney. Trk receptors were
      detected in paraffin-embedded tumor tissue sections by means of a pan-Trk
      polyclonal antibody raised against the 14 carboxy-terminal residues of gp140trk,
      and trk A, B, and C transcripts were specifically detected by polymerase chain
      reaction-based amplification on cDNAs derived from tumor RNA with MuLV reverse
      transcriptase. Reactivity to the pan-Trk antibody was exhibited by six ES tumors,
      the three NBs, and the single PHEO and SCHW cases; immunoreactivity was
      restricted to differentiated tumors, in the case of ES. Tumor types positive for
      immunostaining were also distinguished by containing transcripts of TRK genes.
      However, the trk A, B, and C expression pattern of ES differed from that of NBs,
      PHEO, and SCHW. Transcripts of trk A, B, and C were detected in seven, four, and
      one case of ES, respectively, and in five, two, and five cases of NB, PHEO, and
      SCHW, respectively. Interestingly, all differentiated ES tumors contained trk A
      transcripts. Tumors of neuroectodermal phenotype and/or derivation were thus
      characterized by a distinct consensus expression pattern: trk A+/B-/C+ for
      differentiated ES and trk A+/B-/C+ for NB-PHEO-SCHW. These results indicate that
      the TRK gene family is frequently activated in ES; they also suggest that Trk A
      receptor is a feature of ES with neural differentiation, whereas Trk B and C
      receptors seem to be present in undifferentiated ES.

PMID- 9028733
TI  - Genomic imprinting and the endometrial cycle. The expression of the imprinted
      gene H19 in the human female reproductive organs.
AB  - H19 is an imprinted maternally expressed gene, which is not translated to protein
      and functions as an RNA molecule. It is closely related to the oppositely
      imprinted paternally expressed insulin-like growth factor 2 (IGF-2). While the
      biological function of H19 is not understood IGF-2 is a growth factor that plays
      a role in human follicular and endometrial differentiation. We examined the
      expression of H19 in the endometrium and ovary during the menstrual cycle by in
      situ hybridization applied to paraffin sections of human endometrium and ovaries
      at different stages of differentiation. In the endometrium, H19 expression was
      confined to the stroma and fluctuated with endometrial dating to reach its peak
      in the late secretory stage. IGF-2 was also prominently expressed in late
      secretory endometrium, but its expression was evident both in the stroma and
      glandular epithelium. Expression of H19 was not found in primordial, primary, and
      preantral follicles of the ovary, but prominent expression was evident in the
      theca of antral and cystic atretic follicles, and focal expression was noted in
      the granulosa of corpora lutea. An association between H19 expression during the
      menstrual cycle and the differentiation state of the human female reproductive
      tract, which is under hormonal control, is suggested.

PMID- 9028734
TI  - Demonstration of cytoplasmic tyrosinase mRNA in tissue-cultured cells by reverse
      transcription (RT) in situ polymerase chain reaction (PCR) and RT PCR in situ
      hybridization.
AB  - To evaluate the specificity and applicability to the study of human tumor cells
      of the reverse transcription (RT) in situ PCR and RT polymerase chain reaction
      (PCR) in situ hybridization techniques, we examined five melanoma cell lines and
      five nonmelanoma lines for tyrosinase mRNA using primers specific for tyrosinase.
      Each procedural step was optimized and minutely controlled, and results from the
      in situ techniques and solution-phase RT-PCR were compared. All melanoma lines
      showed a specific pattern of perinuclear cytoplasmic reaction not seen in
      nonmelanoma lines. There was exact agreement between the results from the RT in
      situ PCR and RT-PCR in situ hybridization techniques and those from solution
      phase RT-PCR. Ribonuclease digestion abolished cytoplasmic staining, as did
      omission of the reverse transcriptase step. Nuclear staining was seen in melanoma
      and nonmelanoma lines, apparently as a result of DNA synthesis from repair
      replication and mispriming or nonspecific amplification. Neither high
      concentrations of deoxyribonuclease nor long incubation periods abolished this
      effect completely. Demonstration of cytoplasmic mRNA by RT in situ PCR and RT-PCR
      in situ hybridization specifically identifies cells of melanocytic lineage.

PMID- 9028735
TI  - A nonradioactive method of in situ hybridization that uses riboprobes and
      paraffin-embedded tissue and its combination with immunohistochemistry.
AB  - Current research into cytokine production in tissue sections relies on the
      detection of cytokine proteins using a variety of immunohistochemical methods.
      The disadvantages of this technique are that precise localization to a particular
      cell is difficult and it is uncertain whether the cells detected by this method
      are the origin or target of the cytokine or rather have nonspecifically absorbed
      the secreted cytokine. This question can be clarified using in situ
      hybridization, but current techniques are insensitive, poorly localizing, or time
      consuming. Biotin-labeled riboprobes were generated from cDNA fragments
      sandwiched between two RNA polymerase promoters (SP6 and T7 RNA polymerases)
      using a commercial riboprobe generation kit containing biotin-labeled UTP. The in
      situ hybridization technique was used to demonstrate cytokine mRNA in a range of
      tissues containing an inflammatory infiltrate and with a range of cytokine
      probes. This technique of in situ hybridization was combined with
      immunohistochemistry using an immunoalkaline phosphatase technique to show the
      powerful combination of these two techniques. The biotin-labeled riboprobes were
      sensitive enough to detect a range of cytokine mRNAs in a variety of tissue
      sections. The technique can be completed over a 24-h period and produces a stable
      color product that can be stored for long periods and can be quantitated using
      image analysis techniques. This technique was performed on paraffin-embedded
      tissue as well as cryosections and allowed for the detection of mRNA in archival
      tissue. It was also successfully combined with immunohistochemical techniques to
      determine simultaneously the localization of a cytokine product in particular
      cell lineages. A nonradioactive method for in situ hybridization using biotin
      labeled riboprobes is described; it is capable of detecting mRNA products from a
      range of genes in a variety of tissue samples. An amplification step in the
      method enhances the sensitivity to a level that approaches that of radioactive
      methods, while maintaining the speed, safety, and simplicity of an
      immunoperoxidase detection system. The ability to use paraffin-embedded tissue
      with this method allows for improved tissue architecture and examination of
      archival tissue. These features should ensure greater use of in situ
      hybridization techniques in future research studies.

PMID- 9028736
TI  - Elevated expression of retinoic acid receptor-alpha (RAR alpha) in estrogen
      receptor-positive breast carcinomas as detected by immunohistochemistry.
AB  - Retinoids modulate gene activity, cell growth and differentiation by binding to a
      series of nuclear receptors, i.e., retinoic acid receptors (RARs) or retinoid X
      receptors. Retinoic acid (RA) inhibition of estrogen receptor (ER)-positive
      breast carcinoma seems to be mediated through RAR alpha. Estrogens upregulate RAR
      alpha in ER-positive breast carcinoma cell lines. In this study we examined RAR
      alpha expression in the ER-positive MCF7 and ER-negative MDA-MB-231 human breast
      carcinoma cell lines as well as in 10 ER-negative and 9 ER-positive infiltrating
      ductal breast carcinoma specimens using immunohistochemistry and quantitation by
      image cytometry. MCF7 cells expressed twofold higher levels of RAR alpha protein
      than MDA-MB-231 cells. RAR alpha expression, as detected by immunostaining and
      quantitated by image cytometry, was upregulated in these cells by estradiol. ER
      positive breast carcinoma specimens also exhibited approximately two-fold higher
      RAR alpha levels than their ER-negative counterparts. Thus, RAR alpha expression
      is significantly elevated in ER-positive breast tumors as assessed by detection
      and quantitation using immunohistochemical staining and image cytometry,
      respectively. Whether the decrease in RAR alpha protein levels and loss of RA
      mediated growth inhibition in ER-negative tumor plays a role in the increased
      metastatic potential of ER-negative tumors remains to be determined.

PMID- 9028737
TI  - Analysis of the allele-specific PCR method for the detection of neoplastic
      disease.
AB  - PCR assays for the presence of mutant K-ras or p53 sequences are potentially
      useful as sensitive tests for tumor diagnosis. The technical challenge is to
      design assays sensitive enough to detect a few molecules of mutant DNA yet
      sufficiently specific that a false positive signal is not produced by a 10(5)- or
      10(6)-fold excess of normal DNA. We determined the detection limit of allele
      specific PCR (ASA) as a function of the particular mismatch involved using all 12
      possible mismatches in two different DNA sequence contexts (K-ras codon 12 and
      p53 codon 273). Depending on the identity of the mismatch, mismatched template
      was amplified 10(2)-10(4)-fold less than perfectly matched template. In other
      words, a mutant allele could be detected by ASA if it represented > 1-0.01% of
      the total DNA from that locus. Peptide nucleic acid (PNA) clamping was used to
      improve the K-ras ASA assay. Selective amplification of mutant sequences was
      achieved using a PNA complementary to the normal sequence to inhibit the
      amplification of wild-type DNA. PNA clamping followed by ASA resulted in
      significant improvement in sensitivity and specificity, permitting the detection
      of tumor DNA diluted with a 300,000-fold excess of normal human DNA.

PMID- 9028738
TI  - Molecular identification of a partial hydatidiform mole.
AB  - Specimens of a vacuum curettage were microscopically indicated for a hydatidiform
      mole. The combination of three different approaches identified the specimen as a
      partial mole caused by the fertilization of a haploid ovum by sperm containing a
      haploid or diploid nucleus with one or two sets of paternal genetic material.
      Interphase fluorescence in situ hybridization identified three chromosome 1
      centromeres, and DNA flow cytometry revealed a peak with a DNA index of 1.50. The
      combination of flow cytometric cell sorting and microsatellite marker polymerase
      chain reaction proved that in this case two alleles were from paternal origin.
      Because it is known that partial hydatidiform moles have a tendency for
      recurrence, specimens from the same patient of an earlier executed vacuum
      curettage were investigated. Microdissection of the villi was performed before
      DNA isolation in this case as too few villi were present for DNA flow cytometry
      and cell sorting. In this case, no evidence was fond for additional alleles. This
      study shows the diagnostic potential of microsatellite markers for genetic typing
      of hydatidiform moles.

PMID- 9028739
TI  - Clinicopathologic analysis of k-ras, p53, and ERBB-2 gene alterations in
      pulmonary adenocarcinoma.
AB  - We compared PCR-SSCP detected mutations of k-ras (codon 12) and p53 (exons 5-8)
      to ERBB-2 immunostaining and clinicopathologic features in 31 pulmonary
      adenocarcinomas. There were nine tumors (29%) with mutations of ras, 13 tumors
      (42%) with mutations of p53, and three tumors (10%) with mutations of both.
      Neither k-ras nor p53 mutation alone was significantly correlated with stage,
      grade, or survival. However, tumors with k-ras mutation were more frequently
      associated with an invasive growth pattern, defined as > 30% tumor volume
      composed of infiltrative nests of cells within desmoplastic, scar-like stroma [<
      30% volume invasive--1/13 (8%) with k-ras mutation vs. > 30% volume invasive-
      8/18 (44%) with k-ras mutation, p = 0.02]. Accordingly, k-ras mutations were
      observed in only 1/9 (15%) predominantly bronchoalveolar or papillary tumors
      versus 6/22 (28%) acinar or scar carcinoma tumors. All three patients with
      combined k-ras/p53 mutation had advanced stage (III/IV) at presentation and died
      of the disease. In contrast to k-ras, staining for ERBB-2 was more frequently
      observed in tumors exhibiting < 30% invasive growth pattern (12/13, 92%) than in
      tumors with > 30% invasive growth pattern (10/18, 56%, p = 0.03). ERBB-2
      immunoreactivity was more frequent in Stage I (14/15, 93%) versus Stage II-IV
      (8/16, 50%) cases, but it did not correlate with survival. There was a reciprocal
      relationship between k-ras mutation and ERBB-2 staining; only 4/9 (44%) k-ras
      mutated cases were ERBB-2 positive versus 18/22 (82%) cases without k-ras
      mutation (p = 0.005). In contrast, 8/13 cases with p53 mutation were ERBB-2
      positive. We conclude that well-differentiated and less invasive papillary and
      bronchoalveolar tumors are more often ERBB-2 positive/k-ras negative (i.e. at
      codon 12), whereas less well differentiated acinar or scar carcinomas are more
      often ERBB-2 negative/k-ras mutated at codon 12. These findings imply that the
      divergent histogenesis of pulmonary adenocarcinoma may reflect specific
      differences in genetic pathology.

PMID- 9028740
TI  - Inflammatory bowel disease management. Some thoughts on future drug developments.
AB  - This article is intended to stimulate thought and focus on those areas where we
      feel advances in drug therapy for inflammatory bowel disease may occur. It is not
      an extensive review of current practice, although this is considered where it is
      thought to be pertinent to future developments. There are several excellent
      reviews of current practice which we do not attempt to repeat, nor do we give a
      comprehensive set of references, but cite well referenced reviews where
      necessary. New therapeutic developments should ideally stem from an understanding
      of the cause of pathogenesis of a condition; alternatively, established therapies
      may be modified or used as a basis for progress. Since the causes of both
      ulcerative colitis and Crohn's disease remain unknown, most forward thinking on
      drug development must come from current practice, but remain open to novel
      approaches. Our thoughts on possible future treatments for inflammatory bowel
      disease are somewhat selective, and because of their speculative nature are
      unlikely to coincide with those of others-only the future will reveal genuine
      advances as they become incorporated into established practice.

PMID- 9028741
TI  - Drug treatment of Parkinson's disease in the 1990s. Achievements and future
      possibilities.
AB  - Advances in the medical treatment of Parkinson's disease have improved the
      disability related to complications of long term levodopa therapy, including
      motor fluctuations, dyskinesias and neuropsychiatric toxicity. A range of new
      dopamine agonists are in various stages of preclinical and clinical development.
      Cabergoline appears to be effective in improving moderate motor fluctuations, and
      a number of dopamine partial agonists that can act as either agonists or
      antagonists depending on the degree of denervation and receptor sensitivity are
      being investigated. Apomorphine represents a significant advance in the treatment
      of well developed motor fluctuations in selected patients who are able to master
      the technique of subcutaneous administration. The catecholamine-O-methyl
      transferase inhibitors are proving useful in phase III studies in the management
      of patients with moderate motor fluctuations. A role for glutamate antagonists is
      supported by animal and early clinical data, although the poor therapeutic index
      associated with the currently available nonselective, noncompetitive glutamate
      antagonists has prompted a search for more selective antagonists with less
      toxicity. The management of levodopa-induced dyskinesias remains a major
      therapeutic challenge. Some reports of dopamine partial agonists, selective D2
      receptor antagonists and atypical antipsychotics being useful await confirmation.
      Neuropsychiatric toxicity probably remains the major dose-limiting adverse effect
      of levodopa and is a major reason for parkinsonian patients being admitted to
      nursing homes. The development of new atypical antipsychotics with improved
      therapeutic indices, along with the possible use of serotonergic antagonists, may
      improve management of this difficult problem. The challenge will be to fit these
      new forms of treatment into our present range of available drugs and to assess
      their relative role within the emerging framework of functional neurosurgery for
      parkinsonian disability.

PMID- 9028743
TI  - Recognition and management of gliomas.
AB  - Gliomas are the most frequent primary brain tumours. They include astrocytic
      gliomas, oligodendrocytic gliomas, ependymomas and gliomas with mixed cell
      populations. Each glioma type consists of both low-grade and malignant atypical
      varieties. The low-grade tumours occur predominantly in children and young
      adults, and the malignant forms in older people. The presenting symptoms are
      epileptic seizures, headache and mental confusion. Focal neurological symptoms
      and findings, such as hemiparesis, are mostly associated with the malignant
      forms. Magnetic resonance imaging (MRI) scan of the brain with and without
      gadolinium contrast demonstrates the tumour. However, stereotactic biopsy or
      surgical resection is necessary to obtain the correct pathological diagnosis,
      except for diffuse pontine astrocytomas, which have an unmistakeable imaging
      appearance and for which biopsy has substantial risks. Treatment depends on the
      pathological diagnosis. Complete surgical resection may be curative for low-grade
      tumours. Postoperative radiotherapy is recommended for partially resected
      tumours. Most malignant gliomas require aggressive combination therapy with
      radiotherapy and chemotherapy after maximal surgery. The standard initial
      regimens are nitrosourea-based chemotherapies, such as carmustine alone, a
      combination of procarbazine, lomustine and vincristine, or a combination of
      thioguanine, procarbazine, lomustine and hydroxycarbamide (hydroxyurea).
      Unfortunately, the prognosis of malignant gliomas is generally poor despite
      aggressive treatment, because of their infiltrative nature and high relapse rate.

PMID- 9028742
TI  - Physiology of chemotherapy-induced emesis and antiemetic therapy. Predictive
      models for evaluation of new compounds.
AB  - The physiology of emesis has been studied for several hundred years, focusing on
      the different centres involved and the mechanics of expulsion. The vomiting
      centre receives inputs from various emetic detectors such as the gut, the
      vestibular labyrinths and the chemoreceptor trigger zone. Emesis is a common
      disabling effect in motion sickness, postoperative conditions and in radio- and
      chemotherapy. Our current understanding of the mechanisms has been provided
      mainly by the recent introduction of serotonin 5-HT3 receptor antagonists into
      therapeutic use. Nevertheless, despite the considerable advances made in the
      understanding of the different pathways involved in emesis, there are number of
      areas that still require experimental investigation. Different animal and human
      models are available to study the physiology of emesis and to evaluate the
      antiemetic activity of new compounds, but they need to be predictors of clinical
      situations.

PMID- 9028744
TI  - Recognition and optimum treatment of brucellosis.
AB  - Brucellosis (infection with Brucella spp.) is a common zoonosis in many parts of
      the world. Human brucellosis is a multisystem disease that may present with a
      broad spectrum of clinical manifestations. Treatment of brucellosis must
      effectively control acute illness and prevent complications and relapse. The
      choice of regimen and duration of antimicrobial therapy should be based on the
      presence of focal disease and underlying conditions which contraindicate certain
      specific antibiotics. The regimen of first choice is combination therapy with
      doxycycline for 45 days and streptomycin for 14 days. Gentamicin or netilmicin
      for the first 7 days may be substituted for streptomycin. Second-choice regimens
      consist of combinations of doxycycline and rifampicin (rifampin) for 45 days, or
      monotherapy with doxycycline for 45 days. Surgery should be considered for
      patients with endocarditis, cerebral or epidural abscess, spleen abscess or other
      abscesses which are antibiotic-resistant. Tetracyclines are generally
      contraindicated for pregnant patients and children < 8 years old. Rifampicin 900
      mg once daily for 6 weeks is considered the drug of choice for treating
      brucellosis in pregnant women. In children < 8 years old the preferred regimen is
      rifampicin with cotrimoxazole (trimethoprim-sulfamethoxazole) for 45 days. An
      alternative regimen consists of a combination of rifampicin for 45 days with
      gentamicin 5 to 6 mg/kg/day for the first 5 days.

PMID- 9028745
TI  - Triamcinolone acetonide. A review of its pharmacological properties and
      therapeutic efficacy in the management of allergic rhinitis.
AB  - Triamcinolone acetonide is a synthetic glucocorticoid which has been formulated
      as both an aerosol and an aqueous metered-dose pump spray for nasal inhalation in
      the treatment of allergic rhinitis. Nasally administered triamcinolone acetonide
      is not significantly absorbed into the systemic circulation and does not suppress
      hypothalamic-pituitary-adrenal (HPA) axis function at therapeutic dosages.
      Clinical trials with either formulation have shown that once-daily triamcinolone
      acetonide 110 to 220 micrograms reduces symptoms of allergic rhinitis within the
      first day of administration. Once symptoms are under control, the dosage of
      aqueous triamcinolone acetonide may be reduced from 220 to 110 micrograms/day
      without loss of effect. Both aqueous and aerosol formulations of triamcinolone
      acetonide are significantly more effective in relieving symptoms and reducing
      nasal eosinophil influx than placebo. Once-daily intranasal triamcinolone
      acetonide 220 micrograms/day produced similar reductions from baseline in nasal
      symptoms of allergic rhinitis, when measured both subjectively (visual analogue
      scales) and objectively (anterior rhinomanometry), to those seen with
      beclomethasone 84 to 168 micrograms twice daily, fluticasone 200 micrograms once
      daily or flunisolide 100 micrograms twice daily for 3 to 12 weeks. Furthermore,
      triamcinolone acetonide aerosol 220 micrograms/day was significantly more
      effective at reducing the nasal symptoms of allergic rhinitis than the oral
      antihistamines loratadine and astemizole (both 10mg daily) and was equally as
      effective in reducing the associated ocular symptoms. The use of intranasal
      triamcinolone acetonide and oral loratadine in combination did not confer any
      additional advantage over triamcinolone acetonide alone. Triamcinolone acetonide
      [110 to either 220 micrograms/day (aqueous) or 440 micrograms/day (aerosol)] was
      well tolerated in clinical trials; headache and epistaxis were the only adverse
      events considered possibly or probably related to aerosol therapy in a 1-year
      study (110 to 440 micrograms/day). Therefore, in accordance with the
      recommendations from the International Rhinitis Management Working Group
      regarding the use of nasal glucocorticoids, triamcinolone acetonide may be
      considered a first-line therapy option in adults with moderately severe seasonal
      allergic rhinitis with predominantly nasal symptoms and also in children and
      adult patients with perennial allergic rhinitis.

PMID- 9028746
TI  - Olanzapine. A review of its pharmacological properties and therapeutic efficacy
      in the management of schizophrenia and related psychoses.
AB  - Olanzapine is a thienobenzodiazepine derivative which displays efficacy in
      patients with schizophrenia and related psychoses. It has structural and
      pharmacological properties resembling those of the atypical antipsychotic
      clozapine and an improved tolerability profile compared with the classical
      antipsychotic haloperidol. In several large, well controlled trials in patients
      with schizophrenia or related psychoses, olanzapine generally 5 to 20 mg/day was
      at least as effective as haloperidol (5 to 20mg) and more so than placebo, as
      assessed by overall rating scales for psychoses. Olanzapine improved negative
      symptoms to a greater extent than haloperidol in 2 of 3 comparative trials,
      including the largest trial. Efficacy of olanzapine has a rapid onset (within 1
      to 2 weeks). Its clinical benefits appear to be maintained for treatment periods
      of up to 1 year, as shown by analysis of the extension phase of several trials
      demonstrating decreased probability of hospitalisation over this period compared
      with haloperidol. Preliminary data suggest the drug may also improve quality of
      life. Olanzapine was associated with significantly fewer adverse movement
      disorders (e.g. akathisia, dystonia, hypertonia, extrapyramidal symptoms) than
      haloperidol. There have been no reports of agranulocytosis (as occurs with
      clozapine) or any other haemotoxicity attributed to olanzapine, and the drug has
      shown minimal effect on prolactin levels. Transient increases in levels of
      hepatic transaminases seem to be clinically important. The only events recorded
      more frequently during olanzapine than during haloperidol therapy were weight
      gain, dry mouth and increased appetite. Although the antipsychotic activity of
      olanzapine has been well demonstrated. Its efficacy in refractory schizophrenia
      and its place relative to other atypical antipsychotics remain to be determined.
      Nevertheless, if the long term tolerability profile of olanzapine is confirmed,
      the drug should provide a valuable therapeutic alternative in the management of
      schizophrenia and related psychoses.

PMID- 9028748
TI  - Analysis of very early jugular bulb oximetry data after severe head injury:
      implications for the emergency management?
AB  - Jugular bulb oximetry provides the first bedside available information on
      cerebral oxygen utilization. An extensive analysis was made of all initial
      jugular bulb oximetry data obtained in 150 patients within the first 12 h after
      severe traumatic brain injury. These data revealed initial abnormal jugular bulb
      saturation values in 57 patients (= 38% of study population), with a predominance
      of jugular bulb desaturation (observed in 45 patients). This confirms earlier
      reports that revealed a high incidence of disturbed and inadequate cerebral
      perfusion in the first hours after brain injury. Jugular bulb desaturation was
      especially related to systemic causes (such as a lowered cerebral perfusion
      pressure observed in 29 patients, and a lowered arterial carbon dioxide tension
      in 24 patients). These findings could have important implications for the
      emergency management of severely head-injured patients, as outcome might possibly
      be improved by better attention to all systemic factors that might reduce
      cerebral perfusion in the early hours after traumatic insult.

PMID- 9028749
TI  - Ambulance use, misuse, and unmet needs in a developing emergency medical services
      system.
AB  - Ambulances in Taiwan have always been viewed by medical personnel and the
      population at large purely as transport vehicles. The emergency medical services
      (EMS) system upgrading will require a change of concept. Following emergency
      medical technicians (EMT) training in Keelung, a 400000-inhabitant mid-sized port
      city in northern Taiwan, we began prospective data collection to evaluate the
      patterns of ambulance use, misuse and potential needs within the community. Over
      a 3-month period, 1035 calls, 572 fully documented patient transfers and 17703
      emergency department (ED) visits at the city's largest hospital were collected
      and analysed. The daily call volume was 0.32 per 10000 population with 31.7% of
      all ambulances dispatched resulting in no patient being transferred. The majority
      of patient transports were for trauma (61.2%), with almost all of the no patient
      transfers also following trauma, having been called in by someone passing by or
      witnessing the accident. Of those transported, 27.6% did not require even basic
      EMT care and so were considered misuse. Conversely, the majority of critically
      ill patients presenting to the hospital ED did not arrive by EMS ambulance,
      giving a conservatively projected unmet need of 86%. Despite low call volumes,
      misuse and non-transport, rates appear high. This is because the majority of
      accidents are called-in by passers-by who have no first aid training and a
      cultural aversion to becoming involved. At the same time unmet needs are also
      high, with education required to get the public to change their practice, and
      further study needed to see if this will, in fact, improve outcomes.

PMID- 9028750
TI  - Incidence and preventability of adverse events in the emergency room of an
      orthopaedic traumatologic surgery unit.
AB  - This paper reviews the nature and the frequency of adverse events in the everyday
      functioning of a French trauma emergency unit, and evaluates the feasibility of
      their detection by the means of a daily record review. A senior surgeon
      identified the adverse events by reviewing the complete record with a minimal 6
      months follow-up for every patient attending the emergency unit during a 10-week
      period. To test the reliability of this review, a blind re-review of all records
      corresponding to the detected adverse events, mixed with an equal number of
      controls, was carried out by two independent experts. The review of the 2604
      records identified 210 medical adverse events, most of them occurring early in
      the care process. Sixty-seven per cent of the adverse events involved prevention
      failure, mainly for tetanus but also for thrombosis and rabies. For the other 33%
      it was possible to determine two situations with a high risk of adverse event:
      body contusions following a traffic accident and metacarpo-phalangeal thumb
      sprains. The re-review evaluated the positive predictive value of the initial
      review to be 97.5% and its negative predictive value to be 96%. It is concluded
      that the review of the initial record by a single senior is effective in
      detecting the adverse events. Prevention of two-thirds of them could be possible
      by the implementation and monitoring of protocols.

PMID- 9028751
TI  - Blunt injury of the small intestine and mesentery--the trauma surgeon's Achilles
      heel?
AB  - Eighteen patients with small intestine or mesenteric injury following blunt
      abdominal trauma were operated over a 34-month period. Early diagnosis and
      surgery, less than 6 hours after admission, was achieved in 10 patients (56%),
      seven of whom had haemorrhagic shock and had positive diagnostic peritoneal
      lavage or ultrasonography on admission. Three haemodynamically stable patients
      had a diagnostic abdominal computed tomography. Diagnosis was delayed in eight
      patients (44%) resulting in a gap between admission and surgery that varied from
      20 hours to 46 days. The delay was related to lack of suspicion of injuries in
      haemodynamically stable patients despite a seat-belt sign, or false negative
      abdominal computed tomography. Diagnosis was delayed in six of seven patients
      (86%) where the only injury on admission was an isolated intestinal or mesenteric
      injury. In 11 patients there were associated abdominal or other system injuries.
      Late diagnosis was associated with an increased morbidity and longer hospital
      stay, relating to intestinal and mesenteric injury. In conclusion, a seat belt
      sign is highly suspicious of intestinal or mesenteric injury. Computed tomography
      was unreliable in diagnosing blunt intestinal and mesenteric injuries, and if
      equivocal, should be followed by diagnostic peritoneal lavage if nonoperative
      management is selected. Delayed diagnosis is often related to isolation of
      intestinal and mesenteric injury and results in increased morbidity and hospital
      stay. Every attempt should be made to reach a diagnosis within six hours of
      admission to the trauma unit. A management algorithm is proposed.

PMID- 9028747
TI  - Pravastatin. A reappraisal of its pharmacological properties and clinical
      effectiveness in the management of coronary heart disease.
AB  - Pravastatin is an HMG-CoA reductase inhibitor which lowers plasma cholesterol
      levels by inhibiting de novo cholesterol synthesis. Pravastatin produces
      consistent dose-dependent reductions in both total and low density lipoprotein
      (LDL)-cholesterol levels in patients with primary hypercholesterolaemia.
      Favourable changes in other parameters such as total triglyceride and high
      density lipoprotein (HDL)-cholesterol levels are generally modest. Combination
      therapy with other antihyperlipidaemic agents such as cholestyramine further
      enhances the efficacy of pravastatin in patients with severe dyslipidaemias.
      Available data suggest that pravastatin is effective in elderly patients and in
      patients with hypercholesterolaemia secondary to diabetes mellitus or renal
      disease. The benefit of cholesterol-lowering in terms of patient outcomes is
      currently an area of considerable interest. Recently completed regression studies
      (PLAC I, PLAC II, KAPS and REGRESS) show that pravastatin slows progression of
      atherosclerosis and lowers the incidence of coronary events in patients with mild
      to moderately severe hypercholesterolaemia and known coronary heart disease.
      Large scale primary (WOSCOPS) and secondary (CARE) prevention studies, moreover,
      demonstrate that pravastatin has beneficial effects on coronary morbidity and
      mortality. In WOSCOPS, all-cause mortality was reduced by 22%. Pravastatin is
      generally well tolerated by most patients (including the elderly), as evidenced
      by data from studies of up to 5 years in duration. As with other HMG-CoA
      reductase inhibitors, myopathy occurs rarely (< 0.1% of patients treated with
      pravastatin): approximately 1 to 2% of patients may present with raised serum
      levels of hepatic transaminases. Thus, with its favourable effects on
      cardiovascular morbidity/mortality and total mortality, pravastatin should be
      considered a first-line agent in patients with elevated cholesterol levels,
      multiple risk factors or coronary heart disease who are at high risk of
      cardiovascular morbidity.

PMID- 9028752
TI  - Administration of rectal indomethacin does not reduce the requirement for
      intravenous narcotic analgesia in acute renal colic.
AB  - The aim of this study was to compare the total dose of intravenous pethidine
      required to give satisfactory analgesia to patients with acute renal colic
      between two groups, one of which was also administered rectal indomethacin on
      presentation and one which was not. This was a prospective, randomized, unblinded
      comparison study. Each group contained 39 patients. Group 1 received rectal
      indomethacin 100 mg and intravenous pethidine in 25 mg increments until pain was
      satisfactorily relieved. Group 2 received increments of intravenous pethidine
      alone. The primary endpoint was total pethidine dose required to achieve
      analgesia to the patient's satisfaction. No significant difference in total
      pethidine dose between the groups was found. It was concluded that administration
      of rectal indomethacin does not reduce the total dose of intravenous pethidine
      required to relieve the pain of acute renal colic.

PMID- 9028754
TI  - Benign paradoxical vocal cord adduction presenting as acute stridor.
AB  - We present a case of benign paradoxical vocal cord adduction' presenting to the
      emergency department as acute stridor. This patient received direct laryngoscopy
      at initial presentation documenting inspiratory vocal cord adduction. The
      syndrome is not well known to emergency physicians and, because it often mimics
      life-threatening airway compromise, prompt recognition of the benign nature of
      this syndrome may avert more aggressive airway interventions such as beta
      agonists, steroids, endotracheal intubation and tracheostomy. Successful
      treatment has included relaxation, sedatives and speech therapy to abort the
      acute attack and prevent further recurrence. As direct flexible laryngoscopy is
      more readily available in the emergency department, goals for the future are more
      rapid diagnosis and appropriate treatment of this benign syndrome.

PMID- 9028753
TI  - Early tracheostomy in trauma patients.
AB  - A retrospective analysis of 118 trauma patients who underwent tracheostomy for
      airway and pulmonary management was undertaken. Timing of the procedure was
      defined as early (0-3 days), intermediate (4-7 days), and late (> 7 days). Head
      injury patients received tracheostomy early (p < 0.00003). Aspiration evaluated
      by modified bedside aspiration test was a frequent occurrence in all three groups
      with no difference in incidence (p < 0.34). Pneumonia was less frequent in the
      early group compared with the intermediate and late groups (p < 0.0034). The
      incidence of pneumonia in the early group was not different from that observed in
      early extubated patients (n = 282; p < 0.23). Our study suggests that early
      tracheostomy may decrease pulmonary septic complications in trauma patients.
      Although no change in length of stay can be attributed to the early performance
      of tracheostomy, preventing pneumonia in the intensive care unit setting with its
      resulting high expense is beneficial.

PMID- 9028755
TI  - Accidental embolization of an intravenous cannula in the upper limb: retrieval
      following computed tomography localization.
AB  - Embolization of small foreign body particles from peripheral veins to the heart
      or lungs is an uncommon occurrence and, once released into the circulation,
      localization and retrieval may be difficult. We present a case of accidental
      separation and embolization of a 28 mm long distal portion of a
      polytetrafluoroethylene intravenous cannula that was sited in a superficial right
      wrist vein. The fragment travelled as far as the antecubital fossa prior to the
      application of a tourniquet. It was then accurately located in the cephalic vein
      using contiguous axial computed tomography with reconstructions, and was easily
      retrieved under local anaesthesia. A management approach to this uncommon but
      potentially serious problem is suggested.

PMID- 9028756
TI  - Guidelines for the management of severe head injury. Brain Trauma Foundation.

PMID- 9028769
TI  - Effect of 21-aminosteroid on extracellular energy-related metabolites and amino
      acids after compression injury of rat spinal cord.
AB  - We evaluated in a rat model of severe spinal cord compression the effect of the
      21-aminosteroid tirilazad on extracellular levels of energy metabolites and amino
      acids, until 3 h after injury. The compound was given i.v. 30 min before injury
      (3 mg/kg) and hourly thereafter (1.5 mg/kg). The findings were compared with
      previously reported effects of methylprednisolone. Both treated and untreated
      rats with spinal cord compression showed, at 10 min after injury, a five- to
      sixfold elevation of extracellular lactate above the preinjury level. There was
      no significant difference for lactate, pyruvate or lactate/pyruvate ratio between
      the treated and untreated injured groups at any time point after trauma.
      Glutamate was significantly elevated both in treated and untreated injured rats
      for 20 min after trauma. The mean glutamate level was lower in animals treated
      with 21-aminosteroid. However, there was no statistically significant difference
      between the treated and untreated rats at any time after trauma. There was no
      statistically significant difference between the groups for aspartate, serine,
      glutamine, histidine, glycine, threonine, taurine, alanine and tyrosine. In
      conclusion our findings indicate that, in the injured spinal cord,
      methylprednisolone and the 21-aminosteroid have differences and similarities,
      regarding their effects on energy and amino acid metabolism. The lowering of the
      lactate and arginine levels early after trauma seen with methylprednisolone
      pretreatment was absent after 21-aminosteroid pretreatment. However, the mean
      extracellular level of glutamate was lower with both methylprednisolone and 21
      aminosteroid after injury, although the difference was not statistically
      significant between treated and untreated rats.

PMID- 9028770
TI  - Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver
      mice.
AB  - The phenotypic effect of the weaver mutation in the ventral midbrain of
      homozygous mutants is associated with the progressive loss of dopaminergic
      neurons. To discover whether the number of mesencephalic dopaminergic cells is
      altered in weaver heterozygotes (wv/+), we studied mice between 20 and 365 days
      of age. We counted tyrosine hydroxylase (TH)-immunopositive cells in the
      substantia nigra (SN), retrorubral nucleus (RRN), and ventral tegmental area
      (VTA), and measured cross-sectional areas of neuronal somata in the SN of wv/+
      and age-matched wild-type controls (+/+). The number of TH-positive cells in the
      wv/+ ventral midbrain was on average 13% lower than normal. Cell loss was
      detected selectively in the SN (12%) and VTA (23%). The areas of somatic profiles
      in the wv/+ nigral neurons were on average reduced by 9.8%. The neuronal losses
      in the SN and VTA correlated with a 13.8% reduction in dopamine level in the
      ventral striatum in wv/+ mice at 14-16 months of age. Our findings imply that a
      single dose of the weaver gene in the mouse is associated with cellular damage
      leading to a chronic deficiency in the mesostriatal dopaminergic system.

PMID- 9028772
TI  - Preferential activation of different I waves by transcranial magnetic stimulation
      with a figure-of-eight-shaped coil.
AB  - Transcranial magnetic stimulation (TMS) over the human primary motor cortex (MI)
      evokes motor responses in the contralateral limb muscles. The latencies and
      amplitudes of those responses depend on the direction of induced current in the
      brain by the stimuli (Mills et al. 1992, Werhahn et al. 1994). This observation
      suggests that different neural elements might be activated by the differently
      directed induced currents. Using a figure-of-eight-shaped coil, which induces
      current with a certain direction, we analyzed the effect of direction of
      stimulating current on the latencies of responses to TMS in normal subjects. The
      latencies were measured from surface electromyographic responses of the first
      dorsal interosseous muscles and the peaks in the peristimulus time histograms
      (PSTHs) of single motor units from the same muscles. The coil was placed over the
      MI, with eight different directions each separated by 45 degrees. Stimulus
      intensity was adjusted just above the motor threshold while subjects made a weak
      tonic voluntary contraction, so that we can analyse the most readily elicited
      descending volley in the pyramidal tracts. In most subjects, TMS with medially
      and anteriorly directed current in the brain produced responses or a peak that
      occurred some 1.5 ms later than those to anodal electrical stimulation. In
      contrast, TMS with laterally and posteriorly directed current produced responses
      or a peak that occurred about 4.5 ms later. There was a single peak in most of
      PSTHs under the above stimulation condition, whereas there were occasionally two
      peaks under the transitional current directions between the above two groups.
      These results suggest that TMS with medially and anteriorly directed current in
      the brain readily elicits I1 waves, whereas that with laterally and posteriorly
      directed current preferentially elicits I3 waves. Functional magnetic resonance
      imaging studies indicated that this direction was related to the course of the
      central sulcus. TMS with induced current flowing forward relative to the central
      sulcus preferentially elicited I1 waves and that flowing backward elicited I3
      waves. Our finding of the dependence of preferentially activated I waves on the
      current direction in the brain suggests that different sets of cortical neurons
      are responsible for different I waves, and are contrarily oriented. The present
      method using a figure-of-eight-shaped coil must enable us to study physiological
      characteristics of each I wave separately and, possibly, analyse different neural
      elements in MI, since it activates a certain I wave selectively without D waves
      or other I waves.

PMID- 9028771
TI  - Dopaminergic innervation of striatal grafts placed into different sites of normal
      striatum: differences in the tyrosine hydroxylase immunoreactive growth pattern.
AB  - When patients with Parkinson's disease initially show symptoms, approximately 80
      85% of their dopaminergic nerve fibers in the striatum have degenerated. It is
      thus of importance to develop strategies to try to rescue the remaining
      dopaminergic neurons and to stimulate them to induce sprouting. In this study the
      goal was to examine whether the different subgroups of dopaminergic neurons in
      the ventral mesencephalon projecting to the basal ganglia have different
      sprouting capacities when stimulated by the trophic effect of a fetal striatal
      graft. Lateral ganglionic eminence was implanted into the lateral ventricle, the
      midportion of dorsal striatum, globus pallidus, or ventral striatum. Solid tissue
      pieces from 13- to 15-mm fetuses were stereotactically implanted into adult
      female Sprague-Dawley rats. At postgrafting week 4 the animals were perfused and
      processed for tyrosine hydroxylase (TH) immunohistochemistry. Transplants placed
      in the lateral ventricle were TH-negative, except for two cases with TH-positive
      fibers where the ependymal layer was disrupted, thereby allowing direct contact
      between the graft and the adjacent host striatum. The transplants placed into
      dorsal striatum were innervated by small patches of dopaminergic nerve fibers.
      Areas between the TH-positive patchy structures remained TH-negative. In grafts
      placed into globus pallidus, both patchy structures and a less dense TH-positive
      nerve fiber network was noted. The TH-positive growth pattern in transplants
      placed in ventral striatum was also divided into patchy and widespread growth.
      Grafts placed in globus pallidus and ventral striatum revealed significantly
      larger areas of TH-positive innervation compared with that measured in grafts
      placed in dorsal striatum and the lateral ventricle. In conclusion, it is
      possible to induce sprouting of TH-immunoreactive nerve fibers from all areas
      examined. The most potent areas to initiate dopaminergic growth were the globus
      pallidus and ventral striatum, where both a patchy dense and a widespread, less
      dense growth was induced. Thus, if using a trophic stimulus to induce sprouting
      from remaining dopaminergic nerve fibers in Parkinson's disease, the preferential
      target to induce sprouting would be ventromedial striatum and growth would be
      guided toward dorsal striatum owing to the enhanced dopaminergic growth
      properties in the ventromedial areas.

PMID- 9028773
TI  - Timing of onset of afferent responses and of use of kinesthetic information for
      control of movement in normal and cerebellar-impaired subjects.
AB  - A coordinated triggering task requiring use of kinesthetic information was
      employed to assess the timing of use of kinesthetic information in normal
      subjects and patients with cerebellar dysfunction. Passive movements of varying
      velocity were imposed in the flexor direction about the metacarpophalangeal joint
      of the right index finger. Subjects attempted to depress a switch with their left
      thumb when the index finger moved past a specified angle that was learned during
      a training session. The velocities ranged from 10 degrees/s to 88 degrees/s in 2
      degrees/s increments. After 200 trials, subjects were then instructed instead to
      react as quickly as possible (reaction-time task) to the onset of movement for an
      additional 200 trials. For the same movements, the timing of onset of responses
      of muscle spindle afferents and cutaneous mechanoreceptors was determined by
      recording the responses of these afferents using microneurography. For slow
      velocities, patients were able to perform similarly to normals but at faster
      velocities patients triggered too late compared with normals. Patients required
      more time to use kinesthetic information than did normal subjects. An estimate of
      kinesthetic processing was not longer in patients. The chief explanation for the
      prolonged time required to use kinesthetic information in patients was that their
      reaction times were prolonged by 93 ms. In addition, the movement time was also
      prolonged, but this accounted for only 23 ms. Impaired motor performance in tasks
      requiring the use of kinesthetic information in cerebellar patients can be
      explained largely by their prolonged reaction times. Muscle spindle afferents
      responded on average much sooner than cutaneous mechanoreceptors. Because of the
      limited time available to perform the kinesthetic triggering task, the role for
      cutaneous mechanoreceptors to provide signals for on-line coordination of
      movement appears limited compared with muscle spindle afferents.

PMID- 9028774
TI  - Parvalbumin-containing cells of the angular portion of the vertical limb
      terminate on calbindin-immunoreactive neurons located at the border between the
      lateral and medial septum of the rat.
AB  - In the septal complex, both parvalbumin and calbindin neurons cocontain GABA. In
      the same area, a large number of GABA-GABA synaptic connections can be observed.
      In order to further characterize their neurochemical nature, as well as the
      extrinsic and/or intrinsic origin of these GABA terminals, the following
      experiments were performed: (1) correlated light- and electron-microscopic double
      immunostaining for calbindin and parvalbumin on septal sections of control rats:
      (2) light microscopic parvalbumin immunostaining of septal sections after
      surgical isolation (5 days) of the septum from its telencephalic or (3)
      hypothalamic afferents; and (4) parvalbumin immunostaining of sections prepared
      from the entire brain 2 days following horseradish peroxidase injection into the
      border between the lateral and medial septum. The results demonstrated that: (1)
      in a well-circumscribed, vertically longitudinal area located between the lateral
      and medial septum, 0.1-0.6 mm anterior to the bregma, a group of calbindin
      containing, nonsomatospiny neurons are surrounded by parvalbumin-immunoreactive
      baskets; (2) these basket-forming axon terminals establish symmetric synaptic
      contacts with their targets; and (3) their cells of origin are not in the medial
      septum, but in the angular portion of the vertical limb. These observations
      indicate that a portion of the septal complex GABA-GABA synaptic connections
      represent functional interaction between two different types of GABAergic
      neurons. The presynaptic GABAergic neurons contain parvalbumin, and the
      postsynaptic GABAergic cells are immunoreactive for calbindin. Furthermore, a
      population of the medial septum/diagonal band parvalbumin neurons project only to
      the hippocampus, while others, which may also send axons to the hippocampus,
      terminate on lateral septum calbindin cells as well.

PMID- 9028775
TI  - The oculomotor integrator: testing of a neural network model.
AB  - An important part of the vestibulo-ocular reflex is a group of cells in the
      caudal pons, known as the neural integrator, that converts eye-velocity commands,
      from the semicircular canals for example, to eye-position commands for the
      motoneurons of the extraocular muscles. Previously, a recurrently connected
      neural network model was developed by us that learns to simulate the signal
      processing done by the neural integrator, but it uses an unphysiological learning
      algorithm. We describe here a new network model that can learn the same task by
      using a local, Hebbian-like learning algorithm that is physiologically plausible.
      Through the minimization of a retinal slip error signal the model learns, given
      randomly selected initial synaptic weights, to both integrate simulated push-pull
      semicircular canal afferent signals and compensate for orbital mechanics as well.
      Approximately half of the model's 14 neurons are inhibitory, half excitatory.
      After learning, inhibitory cells tend to project contralaterally, thus forming an
      inhibitory commissure. The network can, of course, recover from lesions. The
      mature network is also able to change its gain by simulating abnormal visual
      vestibular interactions. When trained with a sine wave at a single frequency, the
      network changed its gain at and near the training frequency but not at
      significantly higher or lower frequencies, in agreement with previous
      experimental observations. Commissural connections are essential to the
      functioning of this model, as was the case with our previous model. In order to
      determine whether a commissure plays a similar role in the real neural
      integrator, a series of electrical perturbations were performed on the midlines
      of awake, behaving juvenile rhesus monkeys and the effects on the monkeys' eye
      movements were examined. Eye movements were recorded using the coil system
      before, during, and after electrical stimulation in the midline of the pons just
      caudal to the abducens nuclei, which reversibly made the integrator leaky. Eye
      movements were also recorded from two of the monkeys before and after a midline
      electrolytic lesion was made at the location where stimulation produced a leaky
      integrator. This lesion disabled the integrator irreversibly. The eye movements
      that were produced by the monkeys as a result of these perturbations were then
      compared with eye movements produced by the model after analogous perturbations.
      The results are compatible with the hypothesis that integration comes about by
      positive feedback through lateral inhibition effected by an inhibitory
      commissure.

PMID- 9028776
TI  - Cortical activation by monaural speech sound stimulation demonstrated by positron
      emission tomography.
AB  - To investigate how auditory input from each ear contributes to spoken language
      processing, cortical activation by monaural speech sound stimulation was examined
      in 12 normal subjects using 15O-labeled water positron emission tomography.
      Regional cerebral blood flow (rCBF) was measured under four different sound
      stimulation conditions: (1) silence, (2) white noise, (3) sequential Japanese
      sentences ("speech"), and (4) Japanese sentences played backward ("reversed
      speech"), and the results were evaluated by statistical parametric mapping (SPM).
      Noise induced significant rCBF increase in the contralateral Heschl's gyrus.
      Speech and reversed speech stimuli caused significant rCBF increase in the
      contralateral Heschl's gyrus and the bilateral superior temporal gyri, with
      contralateral activation broader than that in the ipsilateral hemisphere.
      Monaurally input speech sound signals that reach the contralateral Heschl's gyrus
      may be processed chiefly and phonologically in the surrounding superior temporal
      gyrus in the same hemisphere. Comparison of speech activation with reversed
      speech activation failed to demonstrate a significant difference, which made it
      difficult to identify the area for lexical and semantic processing.

PMID- 9028777
TI  - Effect of intrathecal serotonin on nociception in rats: influence of the pain
      test used.
AB  - The involvement of serotonin (5-HT) in the modulation of nociceptive impulse in
      the spinal cord has been widely studied. However, its activity, considering the
      nature of noxious stimuli and the type of 5-HT receptors involved, merits to be
      further elucidated. The present behavioural study was performed to compare the
      dose-antinociceptive effect relationship of 5-HT in rats, after intrathecal
      (i.t.) injection (10 microliters/rat), using mechanical (paw pressure), thermal
      (tail immersion and tail-flick) and chemical (formalin) pain tests. In rats
      submitted to the paw pressure test, 5-HT was found to possess a dose-dependent
      antinociceptive activity (0.01, 0.1, 1, 10 and 20 micrograms/rat) when
      vocalization threshold was assessed as a pain parameter. A peak effect occurred 5
      min after the injection and the effect was maintained for 45 min. The lowest
      active dose was 0.1 microgram (maximum increase in vocalization thresholds, 23 +/
      3%) and a plateau was observed for 10 micrograms and 20 micrograms (maximum
      increase in vocalization thresholds, 72 +/- 7% and 71 +/- 6%, respectively). When
      paw withdrawal was assessed, 5-HT induced a weak hyperalgesic effect for the
      highest dose (60 micrograms), while other doses were ineffective. In the tail
      immersion (warmth and cold) and tail-flick tests, different doses (0.01, 0.1, 1,
      10, 30, 60 and 100 micrograms/rat) were studied. In the two immersion tests, only
      the highest doses (60 micrograms and 100 micrograms) significantly increased the
      withdrawal thresholds from 5 to 45 min after the injection. The maximum effect
      was observed at 5 min (23 +/- 4% and 21 +/- 6% for 60 micrograms; 27 +/- 3% and
      30 +/- 6% for 100 micrograms in the warmth and cold immersion test,
      respectively). In the tail-flick test, the doses of 30, 60 and 100 micrograms/rat
      dose-dependently and significantly increased the withdrawal thresholds from 5 to
      45 min after the injection, with a maximum effect at 5 min (30 +/- 5% for 30
      micrograms; 37 +/- 6% for 60 micrograms; and 45 +/- 4% for 100 micrograms). In
      the formalin test, 5-HT (10, 25, 50, 75 and 100 micrograms/rat) produced dose
      related antinociception. The nociceptive response (licking of the injected paw)
      was significantly reduced from 25 micrograms (-59 +/- 11%) in the early phase,
      whereas the lowest active dose in the late phase was 50 micrograms (-46 +/- 17%).
      For both phases, a total inhibition was obtained with 100 micrograms. It is
      concluded that the effect of 5-HT on pain tests may differ according to the
      applied stimulus and the parameter assessed; unspecific effects of 5-HT may
      modify motor reactions to noxious stimuli. Mechanical test (assessment of
      vocalization) was the most sensitive to 5-HT. These observations are of
      importance in order to further study the pharmacological mechanisms involved in 5
      HT spinally induced antinociception.

PMID- 9028778
TI  - Reaction times of vertical prosaccades and antisaccades in gap and overlap tasks.
AB  - Horizontal saccadic reaction times (SRTs) have been extensively studied over the
      past 3 decades, concentrating on such topics as the gap effect, express saccades,
      training effects, and the role of fixation and attention. This study investigates
      some of these topics with regard to vertical saccades. The reaction times of
      vertical saccades of 13 subjects were measured using the gap and the overlap
      paradigms in the prosaccade task (saccade to the stimulus) and the antisaccade
      task (saccade in the direction opposite to the stimulus). In the gap paradigm,
      the initial fixation point (FP) was extinguished 200 ms before stimulus onset,
      while, in the overlap paradigm, the FP remained on during stimulus presentation.
      With the prosaccade overlap task, it was found that most subjects (10/13)-whether
      they were previously trained making horizontal saccades or naive-had
      significantly faster upward saccades compared with their downward saccades. One
      subject was faster in the downward direction and two were symmetrical. The
      introduction of the gap reduced the reaction times of the prosaccades, and
      express saccades were obtained in some naive and most trained subjects. This gap
      effect was larger for saccades made to the downward target. The strength of the
      updown asymmetry was more pronounced in the overlap as compared to the gap
      paradigm. With the antisaccade task, up-down asymmetries were much reduced.
      Express antisaccades were absent even with the gap paradigm, but reaction times
      were reduced as compared to the antisaccade overlap paradigm. There was a slight
      tendency for a larger gap effect of downward saccades. All subjects produced a
      certain number of erratic prosaccades in the antitasks, more with the gap than
      with the overlap paradigm. There was a significantly larger gap effect for the
      erratic prosaccades made to the downward, as compared to the upward, target, due
      to increased downward SRTs in the overlap paradigm. Three subjects trained in
      both the horizontal and the vertical direction showed faster SRTs and more
      express saccades in the horizontal directions as compared to the vertical. It is
      concluded that different parts of the visual field are differently organized with
      both directional and nondirectional components in saccade preparation.

PMID- 9028779
TI  - Neuromuscular activation patterns during treadmill walking after space flight.
AB  - Astronauts adopt a variety of neuromuscular control strategies during space
      flight that are appropriate for locomoting in that unique environment, but are
      less than optimal upon return to Earth. We report here the first systematic
      investigation of potential adaptations in neuromuscular activity patterns
      associated with postflight locomotion. Astronaut-subjects were tasked with
      walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from
      their eyes after space flights of 8-15 days. Surface electromyography was
      collected from selected lower limb muscles and normalized with regard to mean
      amplitude and temporal relation to heel strike. In general, high correlations
      (more than 0.80) were found between preflight and postflight activation waveforms
      for each muscle and each subject: however relative activation amplitude around
      heel strike and toe off was changed as a result of flight. The level of muscle
      cocontraction and activation variability, and the relationship between the phasic
      characteristics of the ankle musculature in preparation for toe off also were
      altered by space flight. Subjects also reported oscillopsia during treadmill
      walking after flight. These findings indicate that, after space flight, the
      sensory-motor system can generate neuromuscular-activation strategies that permit
      treadmill walking, but subtle changes in lower-limb neuromuscular activation are
      present that may contribute to increased lower limb kinematic variability and
      oscillopsia also present during postflight walking.

PMID- 9028780
TI  - An immunocytochemical study of calpain II in the hippocampus of rats injected
      with kainate.
AB  - The distributions of the kainate/DL-alpha-amino-3-hydroxy-5
      methylisoxazolepropionic acid (KA/ AMPA) receptors GluR1 and calcium-activated
      neutral protease II (calpain II) in the hippocampus of normal and kainate
      lesioned rats were studied by immunocytochemistry. There was a reduction in GluR1
      immunoreactivity and a slight increase in calpain II immunoreactivity on the
      dendrites of pyramidal neurons in CA fields affected by the kainate at 18 h
      postinjection. Calpain II immunore-activity was associated with amyloid fibrils
      at electron microscopy. These fibrils were most often intracellular, in membrane
      bound profiles, some of which were contacted by axon terminals and were
      identified as degenerating dendrites. There was extensive destruction of
      mitochondrial membranes in degenerating profiles, and accumulations of amyloid
      fibrils were often localised in mitochondria in a calpain-positive profile. This
      was unlike other, calpain-negative degenerating profiles, that contained
      tubulovesicular profiles or multilamellar bodies, where mitochondrial membranes
      were preserved. Many more calpain-positive profiles were observed at electron
      microscopy 6 days after kainate injection. The enzyme was present in macrophages
      and astrocytes in lesioned areas.

PMID- 9028781
TI  - Relation between delayed impairment of cerebral energy metabolism and infarction
      following transient focal hypoxia-ischaemia in the developing brain.
AB  - Phosphorus magnetic resonance spectroscopy (31P MRS) was used to determine
      whether focal cerebral injury caused by unilateral carotid artery occlusion and
      graded hypoxia in developing rats led to a delayed impairment of cerebral energy
      metabolism and whether the impairment was related to the magnitude of cerebral
      infarction. Forty-two 14-day-old Wistar rats were subjected to right carotid
      artery ligation, followed by 8% oxygen for 90 min. Using a 7T MRS system. 31P
      brain spectra were collected during the period from before until 48 h after
      hypoxia-ischaemia. Twenty-eight control animals were studied similarly. In
      controls, the ratio of the concentration of phosphocreatine ([PCr]) to inorganic
      orthophosphate ([Pi]) was 1.75 (SD 0.34) and nucleotide triphosphate (NTP) to
      total exchangeable phosphate pool (EPP) was 0.20 (SD 0.04): both remained
      constant. In animals subjected to hypoxia-ischaemia, [PCr] to [Pi] and [NTP] to
      [EPP] were lower in the 0- to 3-h period immediately following the insult: 0.87
      (0.48) and 0.13 (0.04), respectively. Values then returned to baseline level, but
      subsequently declined again: [PCr] to [Pi] at -0.02 h-1 (P < 0.0001). [PCr] to
      [Pi] attained a minimum of 1.00 (0.33) and [NTP] to [EPP] a minimum of 0.14
      (0.05) at 30-40 h. Both ratios returned towards baseline between 40 and 48 h. The
      late declines in high-energy phosphates were not associated with a fall in pHi.
      There was a significant relation between the extent of the delayed impairment of
      energy metabolism and the magnitude of the cerebral infarction (P < 0.001).
      Transient focal hypoxia-ischaemia in the 14-day-old rat thus leads to a biphasic
      disruption of cerebral energy metabolism, with a period of recovery after the
      insult being followed by a secondary impairment some hours later.

PMID- 9028782
TI  - Mesencephalic neuron death induced by congeners of nitrogen monoxide is prevented
      by the lazaroid U-83836E.
AB  - We explored the effects of congeners of nitrogen monoxide (NO) on cultured
      mesencephalic neurons. Sodium nitroprusside (SNP) was used as a donor of NO, the
      congeners of which have been found to exert either neurotoxic or neuroprotective
      effects depending on the surrounding redox milieu. In contrast to a previous
      report that suggests that the nitrosonium ion (NO+) is neuroprotective to
      cultured cortical neurons, we found that the nitrosonium ion reduces the survival
      of cultured dopamine neurons to 32% of control. There was a trend for further
      impairment of dopamine neuron survival, to only 7% of untreated control, when the
      cultures were treated with SNP plus ascorbate, i.e. when the nitric oxide radical
      (NO.) had presumably been formed. We also evaluated the effects of an inhibitor
      of lipid peroxidation, the lazaroid U-83836E, against SNP toxicity. U-83836E
      exerted marked neuroprotective effects in both insult models. More than twice as
      many dopamine neurons (75% of control) survived when the lazaroid was added to
      SNP-treated cultures and the survival was increased eight-fold (to 55% of
      control) when U-83836E was added to cultures treated with SNP plus ascorbate. We
      conclude that the congeners of NO released by SNP are toxic to mesencephalic
      neurons in vitro and that the lazaroid U-83836E significantly increases the
      survival of dopamine neurons in situations where congeners of NO are generated.

PMID- 9028783
TI  - Hand deviations away from visual cues: indirect evidence for inhibition.
AB  - Previous research has demonstrated that when a stimulus is to be ignored, the
      path of motion towards a target (saccade or manual reach) deviates away from the
      to-be-ignored stimulus. Path deviations in saccade and reaching tasks have,
      however, been observed in very different situations. In the saccade tasks
      subjects initially attended to a cue, then disengaged attention while saccading
      to a target. By contrast, in the selective reaching tasks attention was
      continuously withdrawn from the to-be-ignored stimulus, as this was irrelevant
      throughout the experiment. In the two experiments reported here, cues similar to
      those studied in saccade tasks are examined with selective reaching procedures.
      Experiment 1 shows that when a coloured light-emitting diode cue, upon which
      subjects engage and then subsequently disengage attention, is close to the
      responding hand, the hand deviates away from the cue. Experiment 2 confirms this
      cue avoidance by showing that, compared with central fixation alone, the hand
      veers away from a central cue. These results confirm that the path deviations
      observed in saccades can also be obtained in manual reaching movements. Such
      findings support the notion that eye and hand movements are both affected by
      inhibitory mechanisms of attention.

PMID- 9028784
TI  - Eye acceleration during large horizontal saccades in man.
AB  - The pattern of acceleration was recorded during horizontal saccadic eye movements
      using a light-weight accelerometer fixed to a scleral contact lens. Horizontal
      saccades of 15-20 degrees were dominated by either several pulses of
      acceleration, with a frequency of around 40 Hz. or a single acceleration
      deceleration wave followed by lower amplitude polyphasic activity of about 80 Hz.
      These features are unlikely to be due to slippage or resonance in the contact
      lens-accelerometer system, as very similar patterns of acceleration were
      simultaneously recorded with an accelerometer taped over the closed eyelid of the
      contralateral eye. Analysis of simultaneous surface electromyogram recordings
      indicated that the multicomponent acceleration profiles were the product, at
      least in part of the rhythmic and synchronous modulation of eye muscle discharge
      during saccades.

PMID- 9028785
TI  - Stochastic processes in postural center-of-pressure profiles.
AB  - The stochastic processes of postural center-of-pressure profiles were examined in
      3- and 5-year-old children, young adult students (mean 20 years), and an elderly
      age group (mean 67 years). Subjects stood still in an upright bipedal stance on a
      force platform under vision and nonvision conditions. The time evolutionary
      properties of the center-of-pressure dynamic were examined using basic stochastic
      process models. The amount of motion of the center of pressure decreased with
      increments of age from 3 to 5 years to young adult but increased again in the
      elderly age group. The availability of vision decreased the amount of motion of
      the center of pressure in all groups except the 3-year-old group, where there was
      less motion of the center of pressure with no vision. The stochastic properties
      of the center-of-pressure dynamic were assessed using both a two-process, random
      walk model of Collins and De Luca and an Ornstein-Uhlenbeck model that is linear
      and has displacement governed only by a single stiffness term in the random walk.
      The two-process open- and closed-loop model accounted for about 96% and the
      Ornstein-Uhlenbeck model 92% of the variance of the diffusion term. Diffusion
      parameters in both models showed that the data were correlated and that they
      varied with age in a fashion consistent with developmental accounts of the
      changing regulation of the degrees of freedom in action. The findings suggest
      that it is premature to consider the trajectory of the center-of-pressure as a
      two-process, open- and closed-loop random-walk model given that: (a) the linear
      Ornstein-Uhlenbeck dynamic equation with only two parameters accommodates almost
      as much of the variance of the random walk; and (b) the linkage of a
      discontinuity in the diffusion process with the transition of open- to closed
      loop processes is poorly founded. It appears that the nature of the stochastic
      properties of the random walk of the center-of-pressure trajectory in quiet,
      upright standing remains to be elucidated.

PMID- 9028786
TI  - Pressor response elicited by nose-up vestibular stimulation in cats.
AB  - The purpose of the present study was to determine whether selective activation of
      vestibular receptors produces changes in blood pressure. Blood pressure was
      recorded during trapezoidal head rotations in cats with extensive denervations to
      eliminate nonlabyrinthine inputs that could be produced by the movements. Large
      (50 degrees) nose-up trapezoidal head tilts produced an increase in blood
      pressure of approximately 18 mmHg; ear-down tilt produced little change in blood
      pressure. The changes in blood pressure began approximately 1.4 s after the
      plateau of the stimulus. The responses to nose-up tilt were abolished following
      intracranial transections of the VIIIth cranial nerves. These data suggest that
      vestibular inputs elicited by nose-up movements of the head act to rapidly
      increase blood pressure. This mechanism may contribute to counteracting the
      orthostatic hypotension induced by nose-up body rotation in quadrupeds.

PMID- 9028787
TI  - Retinal projections to the accommodation-related area in the rostral superior
      colliculus of the cat.
AB  - Results of previous studies have indicated that the rostral superior colliculus
      (SC) plays an important part in the control of accommodation. The present study
      was carried out to investigate retinal projections to the accommodation-related
      area in the rostral SC. We injected WGA-HRP into the accommodation-related area
      in the rostral SC of the cat, where accommodative responses were elicited by
      stimulation with weak currents of less than 20 microA. Following injection of WGA
      HRP into the accommodation-related area in the rostral SC, retrogradely labeled
      ganglion cells were observed mainly in the area centralis. Projections from the
      contralateral eye were denser than those from the ipsilateral eye. Almost all
      retrogradely labeled cells were classified as gamma-cells owing to their small
      cell-body diameters and thin dendrites, although a few were classified as alpha
      cells. These findings suggest that the accommodation-related area in the rostral
      SC is located in the portion corresponding to the area of representation of the
      central visual field and receives mainly gamma-cell projections.

PMID- 9028788
TI  - A retrograde double fluorescent tracing study of the levator palpebrae superioris
      muscle in the cynomolgus monkey.
AB  - In the cynomolgus monkey, motoneurons innervating the levator palpebrae
      superioris muscle form a nucleus within the oculomotor nuclei called the central
      caudal nucleus. After double fluorescent neuronal retrograde tracing experiments,
      using fast blue and diamidino yellow as tracers in the levator palpebrae superior
      muscles, labelled motoneurons (30%) were found in an unpaired central caudal
      nucleus. Approximately 2% of the labelled motoneurons were double-labelled. The
      labelled and double-labelled neurons were distributed randomly over the central
      caudal nucleus, lateralization of populations of levator motoneurons within this
      nucleus was not observed. The afferent innervation of the levator palpebrae
      superioris muscle was restricted to the ophthalmic branch area of the gasserian
      ganglion. Primary afferent labelled neurons were absent from the mesencephalic
      nucleus of the fifth nerve. Surprisingly, fast blue was also found in the
      ophthalmic branch area of the contralateral ganglion of Gasser, while diamidino
      yellow was present only ipsilaterally. About 1% of the afferent labelled neurons
      were double-labelled. The results reveal that in the cynomolgus monkey the
      central caudal nucleus is not only topographically but also functionally one
      nucleus. Afferent innervation of the levator palpebrae superioris muscle is
      probably bilaterally organized.

PMID- 9028789
TI  - Attention-related neurons in the supplementary eye field of the macaque monkey.
AB  - This study investigated whether the neuronal activity of a cortical area involved
      in the control of eye fixation is affected by the covert orienting of attention.
      We recorded single-unit activity from the supplementary eye field (SEF) of two
      macaque monkeys performing fixation and peripheral-attention tasks. Ninety-nine
      out of four hundred and fifteen cells were related to eye movements. The other
      neurons showed relationship with postural adjustments, and arm and ear movements.
      Fifty-five neurons were active during fixation (fixation cells) and 44 discharged
      in relation to saccades. The experiments reported here primarily concern the
      fixation cells. The activity of 64% (35/55) of fixation cells started with the
      onset of visual stimulus, before the visual input reached the fovea, and
      continued during active fixation. The activity of 27% (15/55) of fixation cells
      started with the onset of fixation. The activity of 9% (5/55) of fixation cells
      modified their timing trial by trial. Sixty-four percent of the fixation cells
      (35/55) were position-dependent, showing a selective spatial field of activity,
      36% (20/55) were position-independent and characterized by a full spatial field.
      None of the 55 cells showed a visual receptive field. We tested both types of
      fixation cells by means of a peripheral attention task. When attention was
      oriented peripherally toward a target located in the selective spatial field, the
      cells discharged as if the gaze was held toward it. When attention was oriented
      peripherally toward a target, lying outside the selective spatial field the cells
      were inactive as if gaze was held in that position. These results suggest that
      the supplementary eye field neurons may code for oriented attention in space and
      might be involved in the preparation of motor action.

PMID- 9028790
TI  - An intact peripheral nerve preparation for monitoring inputs from single muscle
      afferent fibres.
AB  - A preparation is described that permits the monitoring of activity from
      individual muscle afferent nerve fibres in an intact peripheral nerve in the
      forelimb of the cat. The nerve is a fine branch of the deep radial that supplies
      the indicis proprius muscle. When it is freed from nearby tissue over a length of
      2-5 cm and placed in continuity over a silver hook electrode, it becomes possible
      to identify and monitor the impulse activity from each muscle afferent fibre
      activated by stretch or vibration applied to the muscle tendon or by focal
      mechanical stimulation of the muscle at the presumed site of individual spindle
      receptors. With this preparation it is possible to examine the central actions
      and security of transmission at central synaptic targets for single, identified
      muscle afferent fibres arising in the cat's forearm.

PMID- 9028791
TI  - Human keratin diseases: hereditary fragility of specific epithelial tissues.
AB  - Keratins are heteropolymeric proteins which form the intermediate filament
      cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes
      have been found to cause a variety of human diseases affecting the epidermis and
      other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first
      mechanobullous disease for which the underlying genetic lesion was found, with
      mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes
      less resilient to trauma, resulting in skin fragility. The site of mutation in
      the keratin protein correlates with phenotypic severity in this disorder. Since
      mutations were identified in the basal cell keratins, the total number of keratin
      genes associated with diseases has risen to eleven. The rod domains of suprabasal
      keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma
      (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10
      mutations results in a nevoid distribution of EH. An unusual mutation in the VI
      domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar
      keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause
      epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late
      differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS).
      In the last year or so, mutations were discovered in differentiation specific
      keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations
      occur in pachyonychia congenita type 2. K16 and K17 mutations have also been
      reported to produce phenotypes with little or no nail changes: K16 mutations can
      present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17
      mutations can result in a phenotype resembling steatocystoma multiplex. Recently,
      mutation of mucosal keratin pair K4 and K13 has been shown to underlie white
      sponge nevus (WSN). This year, the first mutations in a keratin-associated
      protein, plectin, were shown to cause a variant of epidermolysis bullosa
      associated with late-onset muscular dystrophy (MD-EBS). An unusual mutation has
      been identified in K5 which is responsible for EBS with mottled pigmentation and
      genetic linkage analysis suggests that the hair disorder monilethrix is likely to
      be due to a mutation in a hair keratin. The study of keratin diseases has led to
      a better understanding of the importance of the intermediate filament
      cytoskeleton and associated connector molecules in maintaining the structural
      integrity of the epidermis and other high stress epithelial tissues, as well as
      allowing diagnosis at the molecular level thus facilitating prenatal testing for
      this heterogeneous group of genodermatoses.

PMID- 9028792
TI  - Attachment, spreading and migration of melanoma cells on vitronectin. The role of
      alpha V beta 3 and alpha V beta 5 integrins.
AB  - Recent in situ studies suggest the alpha V beta 3 integrin is a tumour
      progression marker in melanoma. We analyzed 5 human melanoma cell lines for their
      expression of the vitronectin binding alpha V beta 3 and alpha V beta 5 integrins
      using flow cytometry. The role of these receptors in cell attachment, spreading
      and migration was investigated using attachment assays, video time lapse
      spreading and migration assays and with function blocking monoclonal antibodies.
      Cell lines derived from later stages of tumor progression exhibited high levels
      of alpha V beta 3 expression, whereas no similar correlation with alpha V beta 5
      expression was identified. Cell attachment, spreading and migration response on
      vitronectin correlated well with the expression level of the alpha V beta 3 but
      not the alpha V beta 5 vitronectin receptor. Blocking of the alpha V beta 3
      integrin resulted in a significant decrease in cell attachment, spreading and
      motility whereas the function blocking antibody against the alpha V beta 5
      integrin only inhibited cell attachment in cell lines with the highest level of
      expression of this integrin. Taken together, our study indicates that the level
      of expression of the alpha V beta 3 and alpha V beta 5 integrins is heterogeneous
      in melanoma cell lines and that the alpha V beta 5 integrin, if present, may
      function only during the initial cell attachment whereas the alpha V beta 3 plays
      an important role in cell spreading and cell migration as well.

PMID- 9028793
TI  - Human keratinocytes constitutively express IL-4 receptor molecules and respond to
      IL-4 with an increase in B7/BB1 expression.
AB  - In certain pathological conditions, such as atopic dermatitis, interleukin-4 (IL
      4) can be detected in the skin. As the role of this cytokine in inflammatory skin
      lesions is not completely clear, we investigated its biological effects on skin
      keratinocytes. It was found that freshly isolated as well as cultured
      keratinocytes obtained from normal individuals express mRNA for the IL-4 receptor
      (IL-4R) and produce IL-4R protein, as determined by flow cytometry. Moreover, IL
      4 induced a proliferative response in keratinocytes after 1 day of culture and
      enhanced B7/BB1 expression in these cells. B7-2 (CD86) mRNA and protein were
      neither detected on untreated nor IL-4 treated keratinocytes. In contrast to
      interferon-gamma (IFN-gamma), IL-4 did not induce ICAM-1 (CD54) or HLA-DR
      expression. Keratinocytes which had been treated with IL-4 showed an enhanced
      ability to stimulate allogeneic T-cell proliferation in the presence of
      staphylococcus enterotoxin B (SEB), (p < 0.01). Neutralizing anti-B7/BB1
      monoclonal antibodies did not block this effect. These results indicate that
      other molecules than B7/BB-1. HLA-DR or ICAM-1 on IL-4-activated keratinocytes
      may be involved in T-cell stimulation. In conclusion our results suggest that
      locally produced IL-4, besides modulating keratinocyte membrane molecules, may
      enable keratinocytes to interact with skin infiltrating lymphocytes.

PMID- 9028794
TI  - Melanotropic peptide receptors: membrane markers of human melanoma cells.
AB  - The objectives of this research were to determine whether melanotropin receptors
      are characteristic (constant) membrane markers of human melanoma cells.
      Methodologies were developed to visualize these receptors by fluorescence
      microscopy. Multiple copies (10-20) of both [Nle4,D-Phe7]alpha-MSH, a superpotent
      analog of alpha-melanocyte stimulating hormone (alpha-MSH), and a fluorophore,
      were conjugated to polyvinyl alcohol (PVA). Incubation in the presence of the
      multivalent macromolecular conjugate (FITC-PVA-MSH) resulted in binding of human
      epidermal melanocytes and keratinocytes and human melanoma cells (both melanotic
      and amelanotic) to the fluorescent conjugate. Binding of the conjugate to the
      cells exhibited a unique cluster pattern (capping) suggesting a receptor
      internalization related phenomenon. Most importantly, every cell of every
      melanoma cell line, melanotic or amelanotic, possessed receptors as visualized by
      fluorescence microscopy. Since the cells were not synchronized, some binding
      apparently took place during all phases of the cell cycle. Therefore, receptor
      expression appears not to be cell-cycle dependent. Specificity of binding of FITC
      PVA-MSH was demonstrated by several studies. (i) Binding of the conjugate to
      melanoma cells could be blocked by prior incubation of the cells in the presence
      of the unconjugated hormone analog; [Nle4,D-Phe7]alpha-MSH. (ii) The
      macromolecular conjugate lacking bound ligand (FITC-PVA) did not bind to the
      melanoma cells. (iii) Another peptide, a substance-P analog, attached to the
      substrate (FITC-PVA-SP) failed to bind to the cells. (iv) With the exception of
      keratinocytes, other cells of nonmelanocyte origin (e.g., fibroblasts, spleen,
      liver, kidney cells, and mammary cancer cells, lung cancer cells) did not bind to
      the conjugate. Thus, cell-specific melanotropin receptors appear to be
      characteristic cell surface markers of epidermal melanocytes, keratinocytes, and
      melanoma cells. In several human melanoma cell lines these receptors appeared to
      be functional since [Nle4,D-Phe7]alpha-MSH stimulated tyrosinase activity.
      Fluorescent melanotropin conjugates might prove useful in determining whether all
      human melanoma (primary and metastatic) tumors possess such receptors. These
      receptors might then provide targets for melanotropic peptides for the
      identification, localization, and chemotherapy of melanoma.

PMID- 9028795
TI  - The chemotactic activity of T-lymphocytes in response to interleukin 8 is
      significantly decreased in patients with psoriasis and atopic dermatitis.
AB  - Involvement of T-lymphocytes in the pathogenesis of psoriasis and atopic
      dermatitis is well established. The question arises as to whether not only tissue
      infiltrating but also circulating T-lymphocytes are involved in the disease
      process. Therefore we sought to determine whether T-lymphocytes from patients
      with psoriasis and atopic dermatitis show abnormal biological behavior to the
      proinflammatory chemokine interleukin 8 (IL-8) in vitro as studied by their
      chemotactic activity. In addition, the expression of T-cell activation markers
      such as HLA-DR and interleukin 2 receptor (IL-2R) were analysed with FACS
      technique. In all, 25 patients with psoriasis (13 patients with severe psoriasis
      and 12 patients with mild psoriasis) and 11 patients with atopic dermatitis were
      investigated. For comparison. T-lymphocytes from 14 healthy controls were tested
      equally. The results show that T-cell chemotactic responses to IL-8 were
      significantly decreased in patients with severe psoriasis as compared to healthy
      controls. T-cells from patients with atopic dermatitis demonstrated an even more
      pronounced decrease in chemotactic response as compared to T-cells from psoriasis
      patients or healthy controls. In contrast, increased expression of activation
      markers HLA-DR and IL-2R were demonstrated in circulating T-cells from patients
      with severe psoriasis and atopic dermatitis in comparison to healthy controls. It
      can be concluded that circulating T-cells in patients with severe psoriasis and
      atopic dermatitis show a decreased in vitro chemotactic response to IL-8.
      Furthermore, the in vivo phenotypic activation state of T-lymphocytes in these
      patients seemed to be associated with their decreased in vitro functional
      capacity.

PMID- 9028796
TI  - Chrysotile asbestos and H2O2 increase permeability of alveolar epithelium.
AB  - The alveolar epithelium contains tight junctions and provides a barrier to
      passage of potentially injurious substances into the pulmonary interstitium.
      Alveolar epithelial injury is hypothesized to be an important early event in the
      pathogenesis of asbestosis. Mechanisms that may contribute to alveolar epithelial
      cell injury following asbestos exposure include the physicochemical interactions
      between asbestos fibers and cells, and the generation of reactive oxygen species
      such as hydrogen peroxide (H2O2). The present study examined changes in
      transepithelial resistance (Rt) (a measure of barrier function) and permeability
      of alveolar epithelium after chrysotile asbestos and H2O2 exposure. Alveolar
      epithelial cell monolayers, obtained from isolation of rat alveolar type II cells
      and grown on porous supports, were exposed to chrysotile asbestos or polystyrene
      beads (control) at concentrations of 5, 10, and 25 micrograms/cm2 for 24 h. In
      separate experiments, monolayers were exposed to H2O2 at concentrations of 50,
      75, and 100 microM for 1 h Rt was measured using a voltohmmeter. Prior to
      treatment, monolayers had a high Rt (> 2000 ohms.cm2). Permeability was assessed
      by measuring flux of [3H]sucrose from apical to basolateral compartments.
      Cytotoxicity was evaluated by lactate dehydrogenase (LDH) and preincorporated
      [14C]adenine release. The morphological integrity of the monolayers was evaluated
      by scanning electron microscopy. Chrysotile asbestos and H2O2 exposure resulted
      in dose-dependent decrease in alveolar epithelial Rt and increases in
      permeability under conditions that did not result in over cytotoxicity. These
      results demonstrate that both chrysotile asbestos and H2O2 have effects on
      alveolar epithelial Rt and permeability and suggest a potential role for the
      alveolar epithelium in mediation of asbestos-induced pulmonary interstitial
      disease.

PMID- 9028797
TI  - Intratracheal instillation versus intratracheal-inhalation of tracer particles
      for measuring lung clearance function.
AB  - Effective elimination of particles deposited in the respiratory tract is an
      important defense function to protect the organism from potentially adverse
      effects of inhaled particles. Delivery of radioactively labeled tracer particles
      and subsequent measurement in vivo of their retention in different regions of the
      respiratory tract provides an adequate method for characterizing this defensive
      function. However, the delivery of such tracer particles by inhalation may result
      in some external contamination of the animals and requires specific protective
      measures while working with radioactive aerosols. In this study, 85Sr-labeled
      tracer particles (3 microns) were administered to the lower respiratory tract of
      rats by intratracheal inhalation to avoid external contamination, and also by
      intratracheal instillation in order to compare the 2 technique with respect to
      their suitability for measuring normal and impaired particle clearance rates. It
      was postulated that particle clearance function in the alveolar region can be
      determined equally well with intratracheally instilled particles despite their
      uneven distribution in the lung. For both techniques, rats were anesthesized with
      halothane and the particles were administered via oral intubation. Retention in
      the lower respiratory tract of about 30 micrograms (inhalation) and 6 micrograms
      (instillation) of the administered particles was followed over a period of 180
      days by external counting of lung 85Sr-activity in a collimated detection system.
      To impair alveolar particle clearance rates, groups of rats were subjected to 12
      weeks of inhalation exposure prior to delivery of the tracer particles as
      follows: (1) sham-exposed control; (2) pigment-grade TiO2 particles to induce
      lung overload: (3) ultrafine TiO2 particles: (4) crystalline SiO2 particles
      (cristobalite). The following results were obtained: The long-term retention half
      times (T1/2) of the tracer particles reflecting alveolar clearance consistently
      showed the same ranking of the treatment groups whether measured after
      intratracheal inhalation or instillation. Control values were 66 and 72 days,
      respectively, and significantly prolonged long-term clearance was measured by
      both methods for pigment-grade TiO2 (117 and 99 days), ultrafine TiO2 (541 and
      600 days) and SiO2 (1901 and 1368 days). Comparison of these values between the
      two modes of administration of tracer particles showed no significant
      differences. In contrast, the short-term T1/2 (mucociliary clearance) of the
      intratracheally instilled tracer particles in the different treatment groups were
      variable and did not accurately reflect particle clearance from the conducting
      airways. However, short-term T1/2 after intratracheal inhalation of tracer
      particles were consistent with fast conducting airway clearance, and mucociliary
      clearance appears to be stimulated when alveolar clearance is significantly
      impaired due to particle overload or to effects of cytotoxic particles. The
      results suggest that intratracheal instillation of a low dose (< or = 10
      micrograms) of tracer particles in the rat provides an adequate method for
      reliably determining effects of inhaled toxicants on alveolar particle clearance
      function. Further, intratracheal inhalation of tracer particles is useful for
      measuring both short-term (mucociliary) and long-term (alveolar) particle
      clearance rates in the lower respiratory tract of the rat.

PMID- 9028798
TI  - Differential distribution and increased levels of ras proteins during lung
      development.
AB  - Differential localization of ras proteins and variations in their levels may be
      of importance during lung growth and differentiation. Abundant cell proliferation
      occurs during development of the fetal rat lung. As assessed by flow cytometry
      the proliferative activity declined near birth, followed by a gradual increase in
      cellular proliferation during the subsequent 8 days and a decline to basal levels
      by 15 to 18 days of age. During this period of substantial variations in
      proliferative activity, differences in both the protein content and localization
      of the different ras proteins were observed. The content of N- and K-ras proteins
      in lung homogenates increased 5 to 6-fold in rats 20 days or older, compared to
      fetal levels. The protein levels of the ras proteins remained elevated when
      cellular proliferation decreased to basal levels. As determined by
      immunohistochemistry, the localization of N-ras protein was restricted to keratin
      expressing cells of bronchiolar structures, apparently mainly ciliated cells. In
      contrast, K-ras was found in alveolar cells, probably type I and type 2 cells. H
      ras, but not K- or N-ras, was localized to nonepithelial cells. Thus, different
      ras proteins were localized to different regions of the lung and increased in
      abundance during postnatal development.

PMID- 9028799
TI  - Effect of chronic daily ozone exposure on Clara cell secretory protein mRNA
      expression in the adult rat lung.
AB  - Short-term exposure to the air pollutant ozone results in severe injury to the
      nares, trachea, and centriacinus. Long-term exposure however, leads to a state of
      tolerance that is characterized by remodeling in the centriacinar airways and
      markedly reduced cell necrosis and inflammation. This remodeling consists of
      hypertrophy and hyperplasia of Clara cells with a 2- to 5-fold increase in the
      intracellular content of the major protein synthesized by the Clara cell, Clara
      cell secretory protein (CCSP). Previous in vitro studies suggest that CCSP may
      moderate inflammation and bind reactive cytotoxicants. This study tested whether
      acute and chronic exposure to ozone alters the normal level of expression of the
      CCSP gene. Rats were exposed to ozone, 1 ppm 8 h nightly, for up to 90 days.
      Immunohistochemistry demonstrated repopulation of the alveolar ducts with CCSP
      positive Clara cells and an increase in the intensity of immunoreactive CCSP
      within Clara cells. The results showed that (1) CCSP mRNA expression, GAPDH, and
      beta-actin do not change as a result of ozone injury, (2) mRNA levels are more
      variable as a result of ozone injury and (3) CCSP mRNA expression increases with
      age.

PMID- 9028800
TI  - Neutrophil involvement in the retention and clearance of dust intratracheally
      instilled into the lungs of F344/N rats.
AB  - This study evaluated polymorphonuclear leukocyte (PMN) involvement in
      translocation of dust to bronchial lymph nodes after deposition of dust in the
      lungs of control and neutropenic F344/N rats. Rats were rendered neutropenic with
      an intraperitoneal (IP) injection of anti-rat PMN antiserum (APA); control rats
      were injected IP with 0.9% saline solution. Eighteen hours after IP injections,
      control and APA-treated rats were instilled intratracheally with 5 x 10(8)
      microspheres suspended in 0.9% saline solution, which caused an influx of PMNs
      into the pulmonary airspaces of control rats, but not of APA-treated rats. One
      day postinstillation (PI), 77.2% of the microspheres recovered in bronchoalveolar
      lavage fluid (BALF) from control rats were associated with pulmonary alveolar
      macrophages (PAMs) and 18.8% with PMNs; 4.0% were free. In BALF from the APA
      treated rats, 66.3% of the microspheres were associated with PAMs and 0.3% with
      PMNs; 36.3% were free. Two days PI, about 95% of the microspheres in BALF from
      control and APA-treated rats were associated with PAMs; by 4 and 7 days PI,
      essentially 100% were with PAMs. Amounts of microspheres translocated to
      bronchial lymph nodes of control rats were four fold less than in the APA-treated
      rats on days 2, 4, and 7 PI (p < .05). The results suggest that PMNs in pulmonary
      airspaces of F344/N rats phagocytize dust and thereby interfere with the
      mechanism(s) involved in dust penetration into the pulmonary interstitium.

PMID- 9028801
TI  - Airway responses to capsaicin in guinea pigs: role of NK-1 and NK-2 neurokinin
      receptors.
AB  - The role of NK-1 and NK-2 receptors on the pulmonary response to capsaicin in
      guinea pigs was evaluated using intravenous infusion of selective nonpeptide
      antagonists of NK 1 (CP 96345, 300 nmol/kg, and SR 140333, 300 nmol/kg) and NK-2
      (SR 48968, 100 nmol/kg) neurokinin receptors. Maximal values of pulmonary dynamic
      elastance (Edyn) and pulmonary resistance (RL) after capsaicin infusion were
      significantly lower in the presence of SR 48968 (p < .005). Morphometric analysis
      of lungs obtained by quick-freezing showed significant attenuation of airway
      contraction and peribronchiolar edema formation in the presence of NK-2
      antagonist (p < .001). When compared to guinea pigs that received only capsaicin,
      animals that received SR 140333 or CP 96345 showed lower values of Edyn, RL,
      airway contraction, and peribronchiolar edema, but only the difference in Edyn
      values was significant. The combination of NK-1 and NK-2 antagonists was not more
      effective than NK-2 antagonist alone in attenuating capsaicin effects. The
      results suggest that airway effects of capsaicin are mainly mediated by
      activation of NK-2 receptors although NK-1 receptors may also play a role.

PMID- 9028812
TI  - Stress and genetic testing for disease risk.
AB  - Healthy people who believe they are at risk for a life-threatening disease appear
      to carry a substantial stress burden because of threat of disease and uncertainty
      of risk. Testing for risk factors may be helpful by reducing this uncertainty,
      but diseases with multiple causes, like breast cancer, appear to be determined by
      genetic factors and by age, reproductive behavior, exposure to environmental
      toxins, or unknown antecedents. For diseases caused by inherited genetic defects,
      testing brings different benefits and stressors. A model is proposed that
      predicts long-term distress when risk analysis suggests a very high risk, when
      uncertainty is not reduced, when results of testing are at odds with preventive
      actions already taken, and when people who receive a positive, risk-increasing
      result lack strong social support, coping skills, other psychosocial resources,
      or all of these.

PMID- 9028813
TI  - Three-year follow-up after presymptomatic testing for Huntington's disease in
      tested individuals and partners.
AB  - The 3-year psychological effects of presymptomatic DNA diagnosis for Huntington's
      disease are described in 20 identified carriers of the Huntington's disease gene
      (mean age = 31 years), 29 noncarriers (mean age = 32 years), and 37 partners. The
      Intrusion and Avoidance subscales of the Impact of Event Scale (M. J. Horowitz,
      N. Wilner, & W. Alvarez, 1979) and the Beck Hopelessness Scale (A. T. Beck, 1986;
      A. T. Beck, A. Weissman, D. Lester, & L. Trexler, 1974) measured psychological
      distress at 4 time points: baseline (before disclosure of test results) and 1
      week, 6 months, and 3 years after testing. Multivariate testing on course of
      distress revealed similar patterns of intrusive thoughts about Huntington's
      disease over the 3-year follow-up in carriers and noncarriers but showed opposite
      patterns of avoidance at the 6-month assessment. One week after disclosure,
      carriers had increased and noncarriers had decreased levels of hopelessness.
      These effects disappeared after 6 months and did not recur. Carrier partners
      followed the same course of distress as carriers. Carrier partners with children
      were significantly more distressed than those without offspring. Noncarrier
      partners were significantly less distressed than noncarriers after 3 years.

PMID- 9028814
TI  - Predictors of psychological adjustment to genetic testing for Huntington's
      disease.
AB  - In the present study the authors assessed predictors of adjustment to genetic
      testing for Huntington's disease. Fifty-two genetically positive and 108
      genetically negative persons were studied for 1 year following testing.
      Adjustment, defined by hopelessness and depressive symptoms, was measured at 3,
      6, 9, and 12 months after disclosure and was within normal limits for both
      groups. Those less well adjusted had tested positive, were married, had no
      children, or were closer to their estimated ages of onset. The study delineated
      risk factors for psychological distress that should be considered by people
      contemplating testing for Huntington's disease.

PMID- 9028815
TI  - Long-term cognitive and emotional impact of genetic testing for carriers of
      cystic fibrosis: the effects of test result and gender.
AB  - The cognitive and emotional responses to genetic testing for carriers of cystic
      fibrosis (CF) of 241 female and 36 male carriers and a matched sample who had
      received a negative screening result were compared 3 years after testing. The
      main predictor of responses to testing was the type of result received. Gender
      differences in response to screening were also found: Women were more likely to
      feel relieved and less likely than men to feel indifferent, regardless of test
      results. There was an interaction between test results and gender for feeling
      happy and healthy about test results. The greater impact of testing on women may
      reflect gender differences in appraisal or in coping with the threat of being a
      carrier for a genetic disorder.

PMID- 9028816
TI  - Psychological responses to BRCA1 mutation testing: preliminary findings.
AB  - The short-term psychological responses of 60 adult women tested for a BRCA1 gene
      mutation associated with a high risk of breast and ovarian cancer were
      investigated. Participants were members of a large kindred enrolled in an ongoing
      prospective study of the psychosocial impact of genetic testing. Initial results
      from participants who completed both the pretest baseline and the 1-2 week
      posttest follow-up interviews are reported. Gene mutation carriers manifested
      significantly higher levels of test-related psychological distress, as measured
      by the Impact of Event Scale, when compared with noncarriers. The highest levels
      of test-related distress were observed among mutation carriers with no history of
      cancer or cancer-related surgery. Although general distress (state anxiety)
      declined after testing, carriers were more distressed than noncarriers at follow
      up.

PMID- 9028817
TI  - Correlates of psychologic distress in colorectal cancer patients undergoing
      genetic testing for hereditary colon cancer.
AB  - In this article the authors describe the demographic and psychosocial correlates
      of 2 measures of psychologic distress among 200 colorectal cancer patients
      undergoing genetic testing for hereditary nonpolyposis colon cancer. The
      prevalence of symptoms of depression on the Center for Epidemiologic Studies
      Depression (CES-D) Scale was 24%. In multivariate analysis, female sex, less
      formal education, fewer sources of social contacts, and less satisfaction with
      them were associated with high scores on the CES-D Scale. Characteristics
      associated with high scores on the State-Trait Anxiety Inventory were younger
      age, less formal education, non-White race, local-regional stage of disease,
      fewer social contacts, and less satisfaction with them. Information on
      psychosocial correlates of psychologic distress may prove useful in guiding
      genetic counseling sessions, in identifying subgroups that need more intensive
      follow-up, and in developing interventions to facilitate adjustment to genetic
      test results.

PMID- 9028818
TI  - Incorporating biomarkers of exposure and genetic susceptibility into smoking
      cessation treatment: effects on smoking-related cognitions, emotions, and
      behavior change.
AB  - In this article the authors report on the short-term impact of incorporating
      biomarker feedback about exposure and genetic susceptibility into minimal-contact
      quit-smoking counseling (QSC). Four hundred and twenty-seven smokers were
      randomized to 1 of 3 treatments: (a) QSC, (b) QSC + exposure biomarker feedback
      (EBF) about carbon monoxide in exhaled breath, or (b) QSC + EBF + biomarker
      feedback about genetic susceptibility to lung cancer (SBF). We observed
      significant immediate positive effects of SBF, compared with EBF and QSC on
      perceived risk, perceived quitting benefits, and fear arousal. However, at the 2
      month follow-up, there were no group differences in quit rates. SBF did lead to
      significant reductions in the number of cigarettes smoked for smokers who were in
      the preparation stage. Smokers in the EBF and QSC conditions showed reductions in
      depressive symptoms by 2 months, but smokers in the SBF condition did not. In the
      context of QSC, genetic feedback may heighten vulnerability and possibly promote
      distress, but may not immediately enhance quitting in most smokers.

PMID- 9028819
TI  - Compound heterozygosity for Hb Lepore-Boston and Hb Neapolis (Dhonburi) [beta
      126(H4)Val-->Gly] in a patient from Naples, Italy.
AB  - The simultaneous presence of two hemoglobin variants has been detected in a 14
      month-old patient affected by thalassemia intermedia. The two variants were
      characterized by a combination of allele-specific amplification methods and mass
      spectrometric procedures carried out on isolated globins. These were identified
      as Hb Lepore-Boston and Hb Neapolis (also known as Hb Dhonburi) or beta 126
      (H4)Val-->Gly. Hb Lepore-Boston is the most common hybrid variant detected in
      Campania and several cases of Hb Neapolis which causes a mild hypochromic
      microcytic anemia have been identified in this region in the last few years. This
      is the first report of a double heterozygosity involving Hb Lepore-Boston and Hb
      Neapolis.

PMID- 9028820
TI  - Hb Puttelange [beta 140(H19)Ala-->Val] in an Italian man with polycythemia.
AB  - Hb Puttelange [beta 140(H18)Ala-->Val] was found in a 51-year-old Italian man who
      had mild polycythemia. The variant eluted from ion exchange high performance
      liquid chromatography at a position between Hb A and Hb A2. It comprised
      approximately 34% of the total hemoglobin, was weakly unstable and exhibited an
      increased oxygen affinity. Amplification of the beta-globin exons and nucleotide
      sequencing revealed a heterozygosity for a GCC-->GTC mutation in codon 140
      corresponding to an Ala-->Val replacement. This substitution accounts for the
      altered functional properties, probably by producing indirect perturbation of the
      2 3-diphosphoglycerate pocket through the nearby lysine residue at beta 82(EF6).

PMID- 9028821
TI  - Alpha-, beta-, and gamma-mRNA levels in beta-thalassemia; transcriptional and
      translational differences in heterozygotes, homozygotes, and compound
      heterozygotes.
AB  - We have determined the relative levels of alpha-, beta-, and gamma- (G gamma- and
      A gamma-) mRNAs in the reticulocytes of patients with mild beta-thalassemia
      intermedia due to combinations of promoter mutations and a classical type of beta
      thalassemia, as well as in their relatives. The expected differences in the
      alpha/beta-mRNA ratio confirmed the mild suppression of beta-mRNA synthesis,
      particularly in heterozygotes for the -101 (C-->T) promoter mutation and the
      large increase in the relative gamma-mRNA level in compound heterozygotes. A
      significant discrepancy between Hb F and gamma-mRNA levels, observed in
      previously published studies, was confirmed indicating a less efficient gamma
      mRNA translation. When the two different gamma-mRNA (G gamma- and A gamma-)
      levels were determined it was observed that in beta-thalassemia heterozygotes the
      extra gamma-mRNA was primarily of the G gamma type suggesting a more efficient
      translation of the A gamma-mRNA. This difference disappeared in homozygotes and
      compound heterozygotes: both mRNAs (G gamma- and A gamma-) translate with an
      equal efficiency.

PMID- 9028822
TI  - The molecular basis of Hb H disease in Turkey.
AB  - A total of 25 unrelated Hb H patients were studied at the DNA level. Ten
      different genotypes were found to be responsible for the disease. The most
      prevalent alpha-thalassemia-2 determinant was the alpha alpha/-alpha (3.7) kb
      deletion (56%) which was followed by a nondeletional type of alpha-thalassemia,
      namely the pentanucleotide deletion in the 5' first intervening sequence splice
      junction [alpha(-5nt) alpha] (16%). The two most frequent alpha-thalassemia-1
      determinants were alpha alpha/-20.5 kb and alpha alpha/-17.5 kb (MED-I)
      deletions. In two patients, homozygosity for the polyadenylation signal mutation
      [alpha (PA-2)alpha] was found to be responsible for Hb H disease. Clinical and
      hematological expression seems more severe in patients with the alpha (-5nt)
      alpha deletion at the donor site of the first intervening sequence and the
      alpha(PA-2) alpha mutation in trans to an alpha-thalassemia-1 determinant.
      Homozygosity for the alpha (PA-2)alpha mutation was also found to be associated
      with severe phenotype.

PMID- 9028823
TI  - Detection of the alpha-thalassemia-2 (3.7 kb) deletion in DNA extracted from 20
      year-old blood smears.
AB  - Using a polymerase chain reaction procedure we have identified the 3.7 kb alpha
      thalassemia-2 deletion in the DNA that was isolated from slides of blood smears
      stained with Wright's stain some 20 years ago. Details about the procedure are
      presented. The success of this approach depends entirely on the amount of DNA
      that could be isolated; thick smears always gave good data provided they were not
      covered with immersion oil. The success rate in this study was 45%.

PMID- 9028824
TI  - Identification of Mediterranean beta-thalassemia mutations by reverse dot-blot in
      Italians and Egyptians.
AB  - beta-Thalassemia is a significant public health problem in Egypt where over 1000
      of the annual 1.5 million newborns are expected to be affected with this
      disorder. A preventive program of the disease should be multifaceted with its
      technical component based on carrier screening and prenatal diagnosis through
      mutation detection. In addition, it should have an information and educational
      component with the aim of increasing public awareness of the disease. Proper
      selection of the technique(s) to be utilized in such a program is highly
      important. The appropriate technique to be used in screening should be reliable,
      simple and cost effective. It should also circumvent the problem of marked
      heterogeneity of the disease in Egypt. The reverse dot-blot technique has been
      used in the present study for the characterization of mutations in 138 Italian
      and 108 Egyptian thalassemia chromosomes, confirming its reliability as a
      screening method. The technique is now in routine use for thalassemia diagnosis
      in the Microcitemia Center of the Galliera Hospital in Genoa, Italy. Based on
      these results, we recommend the reverse dot-blot method as the technique of
      choice in the preventive program of this disease in Egypt.

PMID- 9028825
TI  - Multivariant confirmation of sickle cell disease using a non-radioactive
      minisequencing reaction.
AB  - A non-radioactive solid-phase minisequencing method for confirmation of abnormal
      hemoglobin variants causing sickle cell disease has been developed. In this
      method amplified 5'-biotinylated target sequences containing normal and mutation
      sites are immobilized onto streptavidin-coated microplates. Detection primers
      corresponding to target sequences are annealed immediately adjacent to the
      mutation site and single-step, hapten-labeled nucleotide primer extension
      reactions are performed. The incorporation of the labeled nucleotide is detected
      through immunological reaction with an enzyme-labeled anti-hapten conjugate and a
      substrate. The method enables confirmation of mutations of the beta-globin gene
      variants (Hbs S, C, E D-Punjab, O-Arab) and the alpha-globin gene variant (Hb G
      Philadelphia). The test was evaluated using characterized dried blood spot
      specimens (n = 100) The advantages of the procedure are easy performance and
      objectiveness. The non-radioactive minisequencing assay will prove helpful for
      genotyping in neonatal screening for hemoglobinopathies and in prenatal and pre
      implantational diagnostics.

PMID- 9028826
TI  - Hb Setif [alpha 94(G1)Asp-->Tyr] in Malta.

PMID- 9028827
TI  - Hb Valletta [beta 87(F3)Thr-->Pro] due to an A-->C substitution at codon 87 in a
      Calabrian family with alpha-thalassemia.

PMID- 9028830
TI  - Isolation of normal human colonic mucosa: comparison of methods.

PMID- 9028829
TI  - The transfection of rabbit articular chondrocytes is independent of their
      differentiation state.

PMID- 9028828
TI  - Stem cells of the respiratory epithelium and their in vitro cultivation.
AB  - Parenchymal (epithelial or mesenchyma) stem cells are rapidly drawing both
      scientific and clinical attention in solid organs like the liver, skin, intestine
      and abdominal mesothelium, just as has been the case in the hematopoietic system.
      For the stem cells of these organs various definitions, markers for
      identification, methods of isolation and in vitro cultivation, and lineage
      mechanisms have been proposed and some of them are now proven to be valid and
      useful. In this article attempts will be made to explore whether there are stem
      cells in the lower respiratory system (from the trachea to the lung periphery)
      and what they look like. Because of its anatomical and functional complexity the
      stem cell concept for the respiratory system has been developing rather slowly.
      Nevertheless, the data available seem to indicate that in analogy to the above
      mentioned organs there is only one type of epithelial stem cells throughout all
      sections of the lower respiratory system during fetal through adult stages. They
      are multipotent for cell differentiation and able to yield lineage progenitors
      for ciliated, goblet, basal. Clara neuroendocrine, alveolar type 1 and alveolar
      type 2 cells.

PMID- 9028831
TI  - WST-1 assay--a simple colorimetric method for virus titration.

PMID- 9028832
TI  - Reconstituted human gingival epithelium: nonsubmerged in vitro model.
AB  - Many studies have shown that human gingival keratinocytes grown in submerged
      culture fail to attain optimal differentiation. This study reports an in vitro
      culture system for oral gingival epithelial cells, in which they are grown at the
      air-liquid interface, on polycarbonate inserts, in the presence of an NIH-3T3
      feeder layer. This model was compared with two submerged culture methods for
      gingival keratinocytes, on type 1 collagen gel and on an NIH-3T3 feeder layer.
      Transmission electron microscopy showed an advanced level of stratification (over
      six layers of cells) for cultures grown at the air-liquid interface.
      Immunofluorescence and electrophoretic patterns showed the presence of
      cytokeratins 10 and 11 in cytoskeletal protein extracts of these cultured
      keratinocytes. In this air-liquid interface culture model, in the presence of NIH
      3T3 feeder cells, keratinocytes can achieve an advanced level of stratification
      and differentiation and a resemblance to in vivo gingiva. The obtention of a
      highly differentiated epithelium will permit in vitro pharmacological studies and
      studies on the biocompatability of certain alloys with the superficial
      periodontium; it will also provide grafts for patients undergoing periodontal
      surgery.

PMID- 9028833
TI  - Characterization of a SV40-transformed rheumatoid synovial fibroblast cell line
      which retains genotypic expression patterns: a model for evaluation of anti
      arthritic agents.
AB  - A chimeric Adenovirus-Simian Virus 40 (AdSV40) containing the large T antigen was
      used to transform rheumatoid synovial fibroblasts. A rheumatoid synovial
      fibroblast cell line was established by infection of primary rheumatoid arthritis
      (RA) synovial fibroblasts at Passage 10 with AdSV40 recombinants followed by
      selection in semisoft agarose cultures. The transformed cells grew anchor
      independent, exhibited continuous proliferation (> 65 passages) in monolayer
      culture, and formed multiple visible foci. The transformed synovial fibroblasts
      showed expression of the simian virus 40 large T antigen in the nucleus as
      determined by immunofluorescence staining. In addition, indirect
      immunofluorescence staining demonstrated that the transformed cells stained
      specifically with a fibroblast-specific antibody 1B10. Studies involving
      expression of metalloproteinases showed that collagenase and stromelysin were
      induced by phorbal 12-myristate 13-acetate (PMA), and such an induction was
      repressed by dexamethasone typical of primary RA fibroblasts. Levels of mRNAs for
      IL-1 beta, TNF-alpha, and c-jun were increased by PMA, and the mRNA transcripts
      of these genes were also repressed by addition of dexamethasone to the culture
      media. Our results indicate that transformed RA synovial fibroblasts display a
      similar gene expression pattern in response to PMA and dexamethasone as observed
      for untransformed primary RA synovial fibroblasts. These transformed rheumatoid
      arthritis synovial fibroblast cells provide an ideal cell culture model in which
      to test the efficacy of novel arthritis gene therapy reagents.

PMID- 9028834
TI  - Generation of a human melanocyte cell line by introduction of HPV16 E6 and E7
      genes.
AB  - Availability of a standard human melanocyte cell line with unlimited growth
      potential and otherwise normal melanocytic properties will greatly facilitate
      research in melanocyte biology and in vitro studies on the etiology of pigmentary
      disorders and melanoma. Using a retroviral vector, E6 and E7 open reading frames
      of human papilloma virus type 16 (HPV 16) have been introduced into cultured
      normal human melanocytes. Cells selected by increased resistance to geneticin
      conveyed by the vector and expressing E6E7 mRNA have been cloned to ensure
      genetic homogeneity. Since their establishment as primary cells, cloned PIG1
      cells have undergone more than twice the amount of population doublings of
      senescent parental cells. Moreover, in passage numbers when parental cells had
      become senescent, proliferation of clonal cells was retained at levels exceeding
      those of normal human melanocytes in third passage by 100%. Further
      characterization has revealed that the cells remain dependent on tetradecanoyl
      phorbol 13-acetate (TPA) for growth and do not proliferate in soft agar nor form
      tumors in nude mice. The antigenic profile of the cells was slightly altered as
      compared to parental cells, but was incomparable to that of M14 melanoma cells.
      Importantly, PIG1 cells contain more melanin pigment than parental cells.

PMID- 9028835
TI  - A colonic tissue architecture assay applied to human colon carcinoma cells.
AB  - A two-component tissue architecture assay system has been devised that tests the
      ability of human colon carcinoma cells to conform to the specific three
      dimensional cell-cell and cell-substratum interactions characteristic of normal
      colonic tissues. Dissociated fetal rat colonic cells (FRCC) were allowed to
      reaggregate in suspension with or without the addition of different proportions
      (0.1%, 1%, and 10% of the total cells) of the human colon carcinoma cell lines,
      SW-1222 and LS-174T. Cellular aggregates obtained after 36 hours, incubation
      exhibited cell sorting by the formation of recognizable epithelial colonic crypt
      like structures with glandular lumens in a mesenchyme-like background.
      Carcinoembryonic antigen (CEA)-positive SW-1222 cells in 10% mixed aggregates
      were organized into numerous well-formed glandular structures with a polarized
      apical distribution of CEA. LS-174T cells, on the other hand, were self-sorted
      but structurally disorganized with a continuous cell surface CEA distribution.
      Pure FRCC and mixed aggregates were implanted under the kidney capsules of Swiss
      nu/nu (nude) or CD-1 nu/nu mice and allowed to grow for a period of 7-10 days.
      Whereas the normal FRCC readily formed colonic tissue, the SW-1222 cells
      exhibited a capacity for differentiation into colonic crypts which became
      progressively less normal and more tumor-like as the proportion of carcinoma
      cells in the aggregates was increased. The LS-174T cells demonstrated poor
      differentiation at all concentrations. Cell surface levels of CEA and the CEA
      family member nonspecific crossreacting antigen (NCA), both overexpressed in
      colon cancer, were higher in LS-174T than in SW-1222 cells, whereas family member
      biliary glycoprotein (BGP), downregulated in colon carcinoma was higher in the SW
      1222 cells. These results thus support the suggestion that deregulated expression
      of CEA family members can be involved in the ability of colonocytes to
      differentiate and conform to normal tissue architecture as assessed by the assay.
      The assay is therefore amenable to genetic analysis of normal and perturbed
      architectural phenotypes.

PMID- 9028837
TI  - Maintenance is hard - a comment on our times in the United States.

PMID- 9028836
TI  - The effects of human leukemia inhibitory factor (hLIF) and culture medium on in
      vitro differentiation of cultured porcine inner cell mass (pICM).
AB  - Isolation and maintenance of porcine embryonic stem (pES) cells have been
      hindered by the inability to inhibit differentiation of the porcine inner cell
      mass (pICM) in vitro. Culture conditions currently in use have been developed
      from mouse ES cell culture and are not effective for maintaining the pICM.
      Optimizing culture conditions for the pICM is essential. We have developed a
      grading system to detect changes in the differentiation status of in vitro
      cultured pICM. Porcine ICMs (Day 7) were isolated by immunosurgery and cultured
      for 4 d in either Dulbecco's modified Eagle's medium (DMEM)-based medium (D
      medium) or DMEM/Ham's F-10 (1:1)-based medium (D/H medium) without human Leukemia
      Inhibitory Factor (hLIF, 1000 iu/ml). Colonies were photographed daily for
      morphological analysis, pICMs were categorized into one of two types based on
      their morphological profile: type A, nonepithelial or type B, epithelial-like.
      Eight investigators evaluated pICM differentiation using standardized
      differentiation profile. Each pICM series was graded on a scale of 1 (fully
      undifferentiated) to 5 (fully differentiated) for each time point.
      Differentiation was verified by alkaline phosphatase activity, cytokeratin
      staining, and scanning electron microscopy. Neither hLIF nor culture medium
      delayed differentiation of pICMs (P = 0.08 and P = 0.25, respectively). The
      grading system employed was an effective tool for detecting treatment effects on
      differentiation of the developing pICM. These results demonstrate that hLIF
      cannot significantly inhibit differentiation of the pICM, and is unlikely to
      assist in porcine ES cell isolation. Future experiments utilizing homologous
      cytokines may prove more beneficial.

PMID- 9028838
TI  - Neonatal ovarian cysts: pathogenesis, diagnosis and management.
AB  - This review discusses problems concerning the neonatal ovary. Neonatal ovarian
      cysts may undergo torsion and amputation. We discuss the pathogenesis, diagnosis,
      and management of these conditions.

PMID- 9028839
TI  - Non-accidental injury or brittle bones.
AB  - When a child presents with one or more unexplained fractures, non-accidental
      injury (NAI) should be considered in the differential diagnosis. This article
      reviews some of the other differential diagnoses, particularly osteogenesis
      imperfecta and the alleged "temporary brittle bone disease".

PMID- 9028840
TI  - Non-accidental injury: confusion with temporary brittle bone disease and mild
      osteogenesis imperfecta.
AB  - Accurate diagnosis of non-accidental injury (NAI) can be reached in the majority
      of cases by careful appraisal of the social and family history, combined with
      painstaking clinical roentgenographic and other imaging evaluations. Careful
      review of the scientific literature clearly indicates that collagen analysis to
      exclude mild forms of osteogenesis imperfecta, especially type IV, is recommended
      only in rare cases in which diagnosis of NAI remains in doubt even after thorough
      evaluation by experienced radiologists and/or other physicians. Until clinical
      research scientifically establishes the existence of temporary brittle bone
      disease, it should remain strictly a hypothetical entity and not an acceptable
      medical diagnosis.

PMID- 9028841
TI  - Occult trauma mimicking metastases on bone scans in pediatric oncology patients.
AB  - BACKGROUND: Tracer-avid osseous lesions are usually considered to represent
      metastases in pediatric oncology patients. However, sites of minor, clinically
      occult, skeletal trauma may be mistaken for osseous metastases. OBJECTIVE: The
      objective of this study was to review our experience with skeletal scintigraphy
      in pediatric oncology patients to determine specificity for metastatic disease.
      Materials and methods. We reviewed 164 bone scans performed on 96 consecutive
      patients (ages 5 months to 23 years) at presentation with malignancy or during
      chemotherapy. Tumors included osteosarcoma (13), Ewing sarcoma (11), lymphoma
      (19), neuroblastoma (12), brain tumors (16), rhabdomyosarcoma (10), renal tumors
      (5), and miscellaneous neoplasms (10). Scintigraphic abnormalities were
      considered metastatic based on radiographic findings, subsequent tumor
      progression, or multiplicity of lesions. Lesions were considered benign when
      spontaneous resolution occurred without change in therapy or radiographs
      demonstrated a traumatic or other benign lesion. RESULTS: Of the 96 patients, 51
      had normal studies or showed only the primary lesion. Of the 45 patients with
      abnormal scintigraphy, 16 (35 %) had metastases and 29 (65 %) had one or more
      focal benign lesions. These lesions included abnormalities due to stress/trauma
      (25), benign neoplasm (2), infection (3), disuse (6), surgery (10) and artifacts
      (4). CONCLUSION: The majority of scintigraphic abnormalities have nonmalignant
      etiologies, most commonly stress reaction and trauma. In patients without known
      extraosseous metastases, one or two skeletal lesions should not be assumed to
      represent metastatic disease.

PMID- 9028842
TI  - Musculoskeletal computed radiography in children: scatter reduction and
      improvement in bony trabecular sharpness using air gap placement of the imaging
      plate.
AB  - The effect of various air gaps on computed radiographic musculoskeletal images
      was investigated using a knee phantom. Scatter to primary radiation ratios were
      measured using the beam stop method at air gaps ranging from 0 to 30 in. (0-762
      mm). Bony trabecular sharpness, line pair resolution, quantum mottle and
      visualization of low-contrast beads in the soft tissues were evaluated. A
      significant reduction of scatter to primary radiation ratio, from a value of
      almost 1 at table top to about 0.4 at 10-in. (254-mm) air gap and about 0.2 at 25
      in. (635-mm) air gap placement of the computed radiography (CR) imaging plate,
      was obtained. A progressive improvement in bony trabecular sharpness and line
      pair resolution, compared with the table top and Bucky images was observed on 10
      in. (254-mm) through 25-in. (635-mm) air gap images. Sharpness of the bony
      trabeculae and line pair resolution were best on the 25-in. (635-mm) air gap
      images. The skin entrance radiation dose does not have to be increased for air
      gap digital radiography. The radiographic noise or quantum mottle is highest on
      the Bucky image, higher on air gap images and minimal on the table top images,
      despite a high scatter to primary radiation ratio at the table top. The lower
      quantum mottle on the table top images allowed for maximal visualization of low
      contrast densities in the soft tissues. Air gap radiography further improves
      musculoskeletal computed imaging by reducing the scatter to primary radiation
      ratio without an increase in the skin entrance dose. For significant reduction of
      the scatter to primary radiation ratio and best evaluation of line pair spatial
      resolution and bony trabeculae, a 25-in. (635-mm) air gap with digital
      radiography would be optimal. For evaluation of low contrast densities in the
      soft tissues, table top placement would be the technique of choice.

PMID- 9028844
TI  - MRI appearance of popliteal cysts in childhood.
AB  - Popliteal cysts are soft fluid-filled lesions of synovial origin which result
      from extrusion of joint fluid into the gastrocnemiosemimembranous bursa. They may
      occur in any age group, but 22-33 % occur in the first 15 years of life. In this
      age group they are rarely associated with intraarticular abnormalities and
      therefore rarely require treatment. This case report shows the magnetic resonance
      imaging (MRI) appearances of a popliteal cyst in two children.

PMID- 9028843
TI  - MR imaging differentiation of benign and malignant peripheral nerve sheath
      tumors: use of the target sign.
AB  - BACKGROUND: T2-weighted MR imaging of soft tissue tumors of neural origin may
      show round lesions with a central hypointensity and a hyperintense rim resembling
      a target. We define the "target sign" as a mass consisting of a solitary target,
      or a multicompartmental mass in which the largest component consists of multiple
      targets. OBJECTIVE: The objective of this study was to determine whether the
      target sign can differentiate benign neurofibromas and their malignant
      counterparts, malignant peripheral nerve sheath tumors. Materials and methods.
      Preoperative T2-weighted MR images of 23 neurofibromas or malignant peripheral
      nerve sheath tumors were retrospectively reviewed in 16 patients, aged 3 weeks to
      20 years (median 15 years), without knowledge of the pathologic diagnosis. The
      presence or absence of a target sign was noted. RESULTS: The target sign was seen
      in all 12 neurofibromas and 1 of the 11 malignant peripheral nerve sheath tumors.
      Statistical analysis showed good differentiation of benign and malignant tumors
      using this sign (chi = 0.91). CONCLUSION: The target sign on T2-weighted MR
      imaging is helpful in differentiating neurofibromas from malignant peripheral
      nerve sheath tumors.

PMID- 9028845
TI  - Radiological signs in newborns exposed to primary Toxoplasma infection in utero.
AB  - A total of 44 181 serum samples from 16 733 pregnant women were analyzed for
      findings suggesting primary Toxoplasma infection. Thirty-seven newborns exposed
      to maternal primary Toxoplasma infection in utero were studied prospectively with
      ultrasound, CT, and MRI for signs of intrauterine infection. Their mothers had
      been treated during pregnancy, and all infants were treated. The children were
      assigned to three groups according to their mothers' serological status, and the
      radiological results were compared with the clinical outcome. Although
      radiological signs were scarce, ultrasound findings combined with maternal
      serology were found to be significantly related to clinical outcome.

PMID- 9028846
TI  - Cerebellar infarction and atrophy in infants and children with a history of
      premature birth.
AB  - BACKGROUND AND OBJECTIVE: We wished to determine the pattern of cerebellar
      disease in children with a history of premature birth and early ultrasound
      evidence of intraventricular haemorrhage and/or parenchymal lesions of the
      cerebral hemispheres. MATERIALS AND METHODS: MRI findings for all premature
      infants examined in a 3-year period (73 patients) were reviewed to determine the
      nature and frequency of lesions of the cerebellum and the results were correlated
      with clinical data. RESULTS: Six cases of unilateral cerebellar infarction were
      identified. These involved the posterior inferior cerebellar territory in each
      case (as well as other territories in two cases). A case of generalised
      cerebellar atrophy and three cases of unilateral cerebellar hemisphere atrophy
      were identified as well. In nine of these ten cases abnormalities were also seen
      elsewhere in the brain. CONCLUSION: The literature describes cerebellar
      infarction in infants and children as rare, but this study shows that it is not
      unusual following perinatal haemorrhagic/ischaemic anoxic injury. It is suggested
      that cerebellar atrophy may also occur as a result of vascular disease.

PMID- 9028847
TI  - Hemorrhage in the cavum septi pellucidi in a full-term neonate.
AB  - A case of hemorrhage in the cavum septi pellucidi presenting as macrocephaly
      secondary to hydrocephalus in a full-term neonate is described. This condition
      has only been reported previously in one premature infant. This unusual location
      of intracranial bleeding has been demonstrated by ultrasonography and MRI. We
      discuss the pathophysiology.

PMID- 9028848
TI  - Power Doppler ultrasound appearances of neonatal ischaemic brain injury.
AB  - Following neonatal ischaemic brain injury, irregular vessels increase in size
      owing to luxury perfusion. These may be demonstrated by conventional colour flow
      Doppler (CFD) imaging at the periphery of the infarcted area. We present a case
      in which power Doppler imaging (PDI) was performed in addition to CFD in a
      neonate with unexplained seizures and which proved more sensitive than CFD in
      demonstrating luxury perfusion. Ultrasound appearances were compared with those
      seen on cranial CT. PDI can be a useful adjunct to conventional CFD examination
      of the neonatal brain in cerebral infarction.

PMID- 9028849
TI  - Mobius syndrome with brain stem calcification: prenatal and neonatal sonographic
      findings.
AB  - The sonographic findings of Mobius syndrome with brain stem calcification are
      presented. Prenatal and neonatal sonography disclosed characteristic hyperechoic
      dots or linear bands in the brain stem representing calcification, which suggests
      prenatal ischemic insult to the brain stem.

PMID- 9028850
TI  - Magnetic resonance imaging with fluid-attenuated inversion recovery pulse
      sequences in MELAS syndrome.
AB  - We report the brain magnetic resonance imaging findings in the case of a 5-year
      old boy with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke
      like episodes (MELAS). Fluid-attenuation inversion recovery (FLAIR) imaging
      revealed multifocal abnormal cortical signals which were difficult to see on
      conventional T1- and T2-weighted images. Although the patient was in an advanced
      clinical stage of disease and had severe cortical atrophy, FLAIR imaging
      demonstrated characteristic findings of MELAS.

PMID- 9028851
TI  - Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI
      findings.
AB  - Vitamin B12 deficiency is known to be associated with signs of demyelination,
      usually in the spinal cord. Lack of vitamin B12 in the maternal diet during
      pregnancy has been shown to cause severe retardation of myelination in the
      nervous system. We report the case of a 14(1)/2-month-old child of strictly
      vegetarian parents who presented with severe psychomotor retardation. This
      severely hypotonic child had anemia due to insufficient maternal intake of
      vitamin B12 with associated megaloblastic anemia. MRI of the brain revealed
      severe brain atrophy with signs of retarded myelination, the frontal and temporal
      lobes being most severely affected. It was concluded that this myelination
      retardation was due to insufficient intake of vitamin B12 and vitamin B12 therapy
      was instituted. The patient responded well with improvement of clinical and
      imaging abnormalities. We stress the importance of MRI in the diagnosis and
      follow-up of patients with suspected diseases of myelination.

PMID- 9028852
TI  - Imaging of pyelonephritis.
AB  - OBJECTIVE: Accurate diagnosis of pyelonephritis using clinical and laboratory
      parameters is often difficult, especially in children. The main aims of this
      prospective study were to compare the value of different imaging techniques
      [renal sonography, cortical scintigraphy with technetium-99m dimercaptosuccinic
      acid (99mTc DMSA) and computed tomography (CT)] in detecting renal involvement in
      acute urinary tract infections and to determine the sensitivity of DMSA scans for
      permanent renal scars 6 months later. MATERIALS AND METHODS: Between February
      1992 and January 1993, 55 children admitted to our pediatric unit with febrile
      symptomatic urinary tract infections were eligible for analysis. Ultrasonography
      (US), DMSA scanning and micturating cystourethrography were performed in every
      case. Only 18 children underwent CT. A second DMSA scan was performed in 48
      children a mean of 7.5 months after the first. RESULTS: US abnormalities were
      found in 25 children (45 %). The first DMSA scan showed a parenchymal aspect
      suggestive of pyelonephritis in 51 patients (93 %). Among the 18 patients studied
      by CT, 14 had abnormalities. Normal US findings did not rule out renal
      parenchymal involvement. Scintigraphy appeared to be more sensitive than CT for
      renal involvement. The frequency and degree of initial renal parenchymal damage
      seemed to correlate with vesicoureteral reflux, but the most severe initial
      parenchymal defects were not associated with marked clinical or laboratory
      manifestations. Repeat DMSA scans, performed on 45 kidneys with abnormalities at
      the first examination, showed resolution in 19, improvement in 16, persistence in
      8 and deterioration in 2. The prevalence of vesicoureteral reflux was not higher
      in patients with renal scarring on the second DMSA scan than in patients whose
      scans showed an improvement. CONCLUSION: DMSA scans should be considered as a
      reference in the detection and follow-up of renal scarring associated with acute
      urinary tract infection as this technique is more sensitive than US and CT, the
      latter being unsuitable because it entails radiation exposure and sedation of
      patients.

PMID- 9028853
TI  - Gastroschisis: a radiological and clinical review.
AB  - A retrospective clinico-radiological review was undertaken of 66 consecutive
      cases of gastroschisis managed at our institution between August 1982 and
      February 1993. The condition's morbidity and mortality were reviewed, as were its
      radiological features and their impact upon management. All patients underwent
      surgery in the first 24 h of life, and the overall survival rate was 92 %. The
      finding of bowel atresia at operation was associated with a particularly poor
      outcome, with only two out of five infants surviving. A minority of infants
      developed serious complications including necrotizing enterocolitis, short-bowel
      syndrome, persistent small-bowel dysfunction and cholestatic jaundice.
      Investigation by plain films, contrast studies and ultrasound examinations was
      necessary and helpful in these patients. Plain film radiography commonly revealed
      bowel-wall thickening and luminal dilatation, frequently accompanied by
      generalised abdominal distension. Small-bowel enema was considered to be superior
      to the conventional follow-through in distinguishing mechanical from functional
      obstruction in infants with persistent bowel dilatation.

PMID- 9028854
TI  - Extraperitoneal abdominopelvic inflammatory pseudotumor: report of four cases.
AB  - We describe four cases of inflammatory pseudotumor seen at our institution in the
      past 4 years. Four children were each found to have a large extraperitoneal mass
      on imaging studies, three of which were in the pelvis. Malignant sarcomatous
      tumors were suspected. Surgical biopsy of each mass, however, revealed
      inflammatory pseudotumor.

PMID- 9028855
TI  - Pyloric volume: an important factor in the surgeon's ability to palpate the
      pyloric "olive" in hypertrophic pyloric stenosis.
AB  - OBJECTIVE: The objective of this study was to determine whether the size of the
      pyloric mass is one of the factors in the surgeon's ability to palpate the
      pyloric "olive". MATERIALS AND METHODS: The ultrasonographic images and medical
      records of 60 infants with surgically confirmed hypertrophic pyloric stenosis
      (HPS) were reviewed. The pyloric diameter (PD) and pyloric length (PL) were
      measured and the pyloric volume (PV) was calculated using the equation PV = 1/4pi
      x (PD)2 x PL. Based on the pediatric surgeon's physical examination the infants
      were divided into two groups: those with and those without palpable pyloric
      masses. RESULTS: Infants with a palpable pyloric mass had an average pyloric
      volume of 3.33 +/- 1.76 mm3, which was statistically larger than those whose
      hypertrophied pylorus could not be palpated (average volume 2.59 +/- 2.07 mm3, P
      < 0.01). There was no statistically significant age difference between the two
      groups. CONCLUSION: Clinical skill of the examiner and other clinical aspects
      (patient cooperation, etc.) determine palpability of the pylorus in HPS. The size
      of the hypertrophied pylorus is also an important factor affecting the
      clinician's ability to palpate the pyloric mass.

PMID- 9028856
TI  - Menetrier's disease evaluated serially by abdominal ultrasonography.
AB  - We report the case of a 3-year-old boy with Menetrier's disease who presented
      with prominent anasarca associated with hypoproteinemia, but no proteinuria. An
      early sonogram of the stomach demonstrated thickening of the gastric wall which
      was found to resolve gradually on serial sonograms. Consequently, we considered
      that the submucosal layer of the gastric wall was particularly thickened as a
      result of Menetrier's disease. A gastric biopsy was performed 18 days after onset
      of the disease, and an electron-microscopic examination of the sample disclosed
      persistent widening of gastric tight junctions by more than 10 nm. The patient
      made a full recovery on supportive treatment in 3 weeks. Ultrasonography provided
      us with a potent tool not only in making the diagnosis, but also in following the
      course of the disease.

PMID- 9028857
TI  - Spiral CT angiography in an infant with severe hypoplasia of a long segment of
      the descending aorta.
AB  - CT angiography, or the spiral CT technique, is a promising minimally invasive
      method of visualising the arterial vascular system and can be applied in children
      in whom ultrasound, MRI and/or angiography or cardiac catheterisation cannot be
      performed, or where an exact diagnosis cannot be made. CT angiography should be
      considered in special cases as a diagnostic alternative to MRI, ultrasound and
      angiography. As an example of the possibilities of CT angiography, a case is
      described in which hypoplasia of the descending aorta was diagnosed and a
      postoperatively encountered perigraft reaction was demonstrated. Perforation of
      the blood vessel could be excluded by CT angiography.

PMID- 9028858
TI  - Adrenobronchial fistula complicating a neonatal adrenal abscess: treatment by
      percutaneous aspiration and antibiotics.
AB  - A case of retroperitoneal pulmonary fistula caused by a neonatal adrenal abscess
      is reported. The adrenal abscess was diagnosed by means of needle aspiration
      which guided the choice of antibiotic therapy. The fistula was demonstrated by
      direct injection of contrast medium into the adrenal abscess. Treatment by needle
      aspiration of the adrenal abscess and intravenous antibiotics was successful.

PMID- 9028859
TI  - Tuberculosis in children with acquired immunodeficiency syndrome.
AB  - With AIDS related tuberculosis in the pediatric population on the rise, we review
      our experience with 14 such children. A brief review of the pertinent literature
      is also presented.

PMID- 9028860
TI  - Dideoxyinosine-induced pancreatitis in human immunodeficiency virus-infected
      children.
AB  - Dideoxyinosine (ddI) is a widely used antiretroviral agent in treatment of HIV
      infection. Pancreatitis is a serious side effect. Two cases are reported, one
      with rapid development of a pseudocyst.

PMID- 9028862
TI  - The mIBG super scan.

PMID- 9028861
TI  - Valproic-acid-associated pancreatitis and hepatic toxicity in children with
      endstage renal disease.

PMID- 9028863
TI  - Nitric oxide generation mediates lipid A-induced oxidant injury in renal proximal
      tubules.
AB  - In previous studies, we found that lipid A, the biologically active component of
      lipopolysaccharide, triggers a rapid release of intracellular calcium, the
      activation of nitric oxide synthase (NOS), and nitric oxide (NO) production in
      rat proximal tubules. This pathway leads ultimately to cell death [as measured by
      the release of lactate dehydrogenase (LDH)], initiated by early generation of NO.
      In the present studies we found that lipid A produces a time- and concentration
      dependent increase in lipid peroxidation [malondialdehyde (MDA) formation] prior
      to cell death. Furthermore, preventing lipid peroxidation protected against cell
      death. Lipid A (50 micro;g/ml) produced significant MDA formation in 30 min. The
      addition of two antioxidants 5 min prior to lipid A completely inhibited MDA
      formation and LDH release at 90 min. Preincubation with 5 mm GSH also
      significantly reduced MDA formation. The involvement of NOS activation in lipid A
      induced lipid peroxidation was established when an NOS inhibitor and an inhibitor
      of intracellular calcium release completely blocked MDA formation. In addition,
      superoxide generation was significantly increased in the presence of lipid A, and
      the involvement of superoxide was established when superoxide dismutase protected
      against oxidant injury. The iron chelators deferoxamine (also a scavenger of
      peroxynitrite) and diethylenetriaminepentaacetic acid prevented lipid A-induced
      lipid peroxidation and cell death, indicating a role for iron and peroxynitrite.
      The addition of an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-3-oxide-1-oxyl, prior to lipid A also completely protected
      tubule cells from lipid peroxidation and subsequent cell death. These results
      indicate that lipid A-stimulated NO generation in the rat proximal tubule
      initiates oxidant injury.

PMID- 9028864
TI  - Signaling pathway triggered by a short immunomodulating peptide on human
      monocytes.
AB  - A short synthetic peptide (Pa) containing a structural motif ("2-6-11" motif)
      present in a number of human extracellular matrix proteins was found to stimulate
      the production of cytokines IL-1alpha, IL-1beta, IL-6, and TNFalpha by human
      peripheral blood mononuclear cells. We have now investigated the signal
      transduction pathway involved in the elicitation of these immunomodulating
      properties on isolated human monocytes. Our results show that active peptide Pa
      provoked phosphoinositide hydrolysis, intracellular calcium elevation, and cAMP
      accumulation. Herbimycin A, an inhibitor of protein tyrosine kinases (PTK),
      markedly reduced these effects of peptide Pa. We have also found that this
      peptide stimulated CREB, NF-kappaB, and AP-1 DNA-binding activity. With the help
      of inhibitors of PTK (herbimycin A), phospholipase C (neomycin sulfate), protein
      kinase C (bis-indolyl maleimide), protein kinase A (H89), and the calmodulin
      antagonist W-7, as well as cholera toxin, an agent that increases intracellular
      cAMP, we showed that cytokine (IL-1alpha, IL-1-beta, IL-6, and TNFalpha)
      production could be modified by the signal transduction pathway triggered by
      peptide Pa on monocytes.

PMID- 9028865
TI  - Reaction of ozone with protein tryptophans: band III, serum albumin, and
      cytochrome C.
AB  - Treatment of red cell ghosts with ozone inhibited both AChE (marking the outside
      of the membrane) and G3PDH (marking the inside of the membrane). There was no
      change in tryptophan fluorescence of the ghosts after the ozone treatment. Band 3
      protein was isolated from the ozone-treated ghosts. The protein was digested with
      trypsin to obtain water soluble peptides from the cytoplasmic N-terminal tail and
      the interhelical loops. Fluorescent peptides included GWVIHPLGLR from the outer
      loop between helices 7 and 8, and peptide WMEAAR from the N-terminal cytoplasmic
      tail. Neither one of these peptides was oxidized by ozone. This was true whether
      or not the ghosts were sealed. We conclude that the position of these tryptophans
      either in the membrane structure, or because of binding to other proteins in the
      cytoplasmic tail, protects them from oxidation by ozone. Treatment of horse heart
      cytochrome c with ozone did not change the absorbance spectrum in the heme region
      or the tryptophan absorbing region. HPLC of the ozone-treated cytochrome c showed
      that cytochrome c was being modified, indicated by a change in the elution time.
      Treatment of cytochrome c with ozone did not change the activity in the NADH
      cytochrome c reductase assay. Digestion of the ozone-treated cytochrome c with
      trypsin gave peptides which demonstrated normal fluorescence. (Cytochrome c has
      abnormally low fluorescence, which is not changed by ozone exposure.) The
      peptides were separated by HPLC. The fluorescence of the tryptophan-containing
      peptide (GITWK) was not decreased by treatment of the cytochrome c by ozone.
      Amino acid analysis of the ozone-treated cytochrome c indicated that methionine
      was oxidized. We conclude that tryptophan in cytochrome c is protected from
      oxidation by ozone because of the interaction with the porphyrin ring. Bovine
      serum albumin and human serum albumin were treated with ozone. There was a
      monotonic decrease in tryptophan fluorescence in both cases. Digestion of BSA
      with trypsin produced two fluorescent peptides. The peptide FWGK was identified
      by coelution with the authentic peptide. The putative peptide AWSVAR was not the
      same as the chemically synthesized peptide. The peptide sequences FWGK and
      "AWSVAR" were both oxidized in ozone-treated bovine serum albumin, with no
      detectable discrimination. Tryptic digestion of the ozone-treated human serum
      albumin produced a single fluorescent peptide, which was oxidized by ozone. The
      putative peptide AWAVAR in the tryptic digest of HSA was distinct from chemically
      synthesized peptide. The oxidation of tryptophans in proteins by ozone is
      markedly influenced by position in tertiary structure, position in membrane
      structure, and by chemical interactions within the protein.

PMID- 9028866
TI  - Complete amino acid sequence of an acidic, cardiotoxic phospholipase A2 from the
      venom of Ophiophagus hannah (King Cobra): a novel cobra venom enzyme with
      "pancreatic loop".
AB  - A phospholipase A2 (OHV A-PLA2) from the venom of Ophiophagus hannah (King cobra)
      is an acidic protein exhibiting cardiotoxicity, myotoxicity, and antiplatelet
      activity. The complete amino acid sequence of OHV A-PLA2 has been determined
      using a combination of Edman degradation and mass spectrometric techniques. OHV A
      PLA2 is composed of a single chain of 124 amino acid residues with 14 cysteines
      and a calculated molecular weight of 13719 Da. It contains the loop of residues
      (62-66) found in pancreatic PLA2s and hence belongs to class IB enzymes. This
      pancreatic loop is between two proline residues (Pro 59 and Pro 68) and contains
      several hydrophilic amino acids (Ser and Asp). This region has high degree of
      conformational flexibility and is on the surface of the molecule, and hence it
      may be a potential protein-protein interaction site. A relatively low sequence
      homology is found between OHV A-PLA2 and other known cardiotoxic PLA2s, and hence
      a contiguous segment could not be identified as a site responsible for the
      cardiotoxic activity.

PMID- 9028867
TI  - Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping
      of an inhibitory monoclonal antibody to P450 2C51.
AB  - The epitope recognized by the inhibitory monoclonal antibody designated 2F5,
      which was raised against P450 2C5, was mapped to amino acids 237-260 by
      immunoblotting using a combination of recombinant antigens and chimeric and
      partial fusion proteins constructed from rabbit P450s 2C2, 2C4, 2C5, and 2C16,
      which are recognized by 2F5, and from 2C1 and 2C3, which are not. When the
      sequence of the epitope for 2F5 (amino acids 237-260) was compared with those of
      other rabbit 2C P450s, a single lysine residue at position 253 appeared to be a
      likely determinant of 2F5 immunoreactivity. Substitution of lysine for glutamic
      acid 253 in P450 2C3 (2C3E253K) conferred immunoreactivity and the ability of 2F5
      to inhibit progesterone metabolism catalyzed by P450 2C3E253K. Sequence alignment
      revealed that this epitope lies in close proximity to the epitope identified for
      LKM-1 autoantibodies to P450 2D6. Based on these results, an antipeptide antibody
      was raised to the corresponding region (amino acids 252-263) of human P450 2C18.
      The resulting antipeptide antiserum recognizes P450 2C18 but not P450 2C8, 2C9,
      or 2C19. However, the antipeptide 2C18 antiserum did not inhibit 2C18-catalyzed
      diazepam N-demethylation. Human 2C P450s were also quantitated by immunoblot
      analysis in a panel of six human liver microsomes using Escherichia coli
      expressed P450s as standards. Analysis of immunoblots indicated that, if present,
      P450 2C18 was expressed at very low levels (<2.5 pmol/mg), whereas P450s 2C8,
      2C9, and 2C19 were easily detected.

PMID- 9028868
TI  - One-electron reduction of chromium(VI) by alpha-lipoic acid and related hydroxyl
      radical generation, dG hydroxylation and nuclear transcription factor-kappaB
      activation.
AB  - Reaction of chromium(VI) with alpha-lipoic acid (reduced form, also called 1,2
      dithiolane-3-pentanoic acid) generated Cr(V) and hydroxyl radical (*OH) as
      measured by electron spin resonance and ESR spin trapping. 5,5-Dimethyl-1
      pyrroline was used as a spin trapping agent. Catalase inhibited the *OH
      generation and enhanced the Cr(V) formation. Superoxide dismutase had an opposite
      effect. H2O2 enhanced the *OH generation and decreased the Cr(V) formation in a
      dose-dependent manner. Metal chelators, EDTA, diethylenetriaminepentaacetic acid,
      deferoxamine, and 1, 10-phenanthroline inhibited *OH radical generation in the
      order of EDTA > 1,10-phenanthroline > DTPA > deferoxamine. Oxygen consumption
      measurements indicated that molecular oxygen was used to generate *OH radical in
      the mixture of Cr(VI) and alpha-lipoic acid. H2O2 and superoxide radical (O2-)
      were involved as reactive intermediates. The *OH radical was generated via Cr(V)
      mediated Fenton-like reaction (Cr(V) + H2O2 --> Cr(VI) + OH- + *OH). HPLC
      measurements show that the *OH radical generated by this reaction is capable of
      generating 8-hydroxyl-2'-deoxyguanosine from 2-deoxyguanosine. Incubation of
      Cr(VI) with cultured Jurkat cells resulted in an activation of DNA binding
      activity of the nuclear factor (NF)-kappaB. Addition of alpha-lipoic acid
      enhanced the NF-kappaB activation, while the *OH radical scavenger, sodium
      formate, inhibited it, showing that alpha-lipoic acid enhanced Cr(VI)-induced NF
      kappaB activation via free radical reactions. The results indicate that while
      alpha-lipoic acid is considered to be an antioxidant, it may be a cellular one
      electron Cr(VI) reductant and could be involved in the mechanism of Cr(VI)
      induced carcinogenesis.

PMID- 9028869
TI  - Multiple routes and regulation by tyrosine phosphorylation characterize the ATP
      dependent transport of 2,4-dinitrophenyl S-glutathione in inside-out vesicles
      from human erythrocytes.
AB  - ATP-dependent efflux routes for 2,4-dinitrophenyl S-glutathione (DNP-SG) were
      investigated using inside-out vesicles from human erythrocytes. Nonlinear double
      reciprocal plots of transport at substrate concentrations ranging from 0.07 to
      500 micro;m indicated that multiple transport routes were operative. Sensitivity
      to naphthyl glucuronide separated [3H]DNP-SG transport into two low-affinity
      components which by computer analysis exhibited Km values of 330 and 1400
      micro;m, respectively. At low substrate concentrations, two high-affinity routes
      were observed. The predominant activity (hMOAT3a) exhibited a Km of 0.18 micro;m
      (Vmax = 22 pmol/min/mg protein), whereas the second activity (MOAT3b) had a Km of
      0.58 micro;m (Vmax = 16 pmol/min/mg protein). High-affinity transport of DNP-SG
      increased substantially (2.5-fold) in vesicles preincubated with genistein or
      other tyrosine kinase inhibitors. Kinetic analyses in vesicles pretreated with 50
      micro;m genistein showed that increased transport resulted from the appearance of
      a new activity (hMOAT3c) with a Km of 0.85 micro;m and a substantially elevated
      Vmax (80 pmol/min/mg protein). At varying concentrations of genistein, a
      progression was observed that was consistent with the conversion of hMOAT3b to
      hMOAT3a and hMOAT3a to hMOAT3c. Phenylarsine oxide, a phosphotyrosine phosphatase
      inhibitor, produced an opposite progression. Specificity studies showed that
      hMOAT3a exhibited the highest affinity for various anionic conjugates, and had a
      notable binding preference for glutathione disulfide. The relative effectiveness
      of the various inhibitors was similar for hMOAT3a, hMOAT3b, and hMOAT3c, as well
      as for a corresponding mMOAT3 activity from L1210 mouse cells. The results show
      that human erythrocytes contain multiple ATP-dependent efflux systems for DNP-SG
      and that separation of these systems can be achieved on the basis of substrate Km
      value and inhibitor and activator specificity. High-affinity transport can
      proceed via three activities which appear to be subforms of a single system with
      differing levels of tyrosine phosphorylation. Multiple hMOAT3 subforms provide
      flexibility for extruding various anionic conjugates and may have evolved in
      erythrocytes to expedite the efflux of GS-SG.

PMID- 9028870
TI  - Functional organization of mammalian hexokinases: characterization of the rat
      type III isozyme and its chimeric forms, constructed with the N- and C-terminal
      halves of the type I and type II isozymes.
AB  - Previous studies have shown that catalytic function is associated with both
      halves of the Type II isozyme of mammalian hexokinase, while the Type I isozyme
      is functionally differentiated into a catalytic C-terminal half and regulatory N
      terminal half. The Type III isozyme has now been shown to be similar to the Type
      I isozyme in its functional organization. Chimeras composed of the N-terminal
      half of Type III hexokinase and the C-terminal half of either Type I or Type II
      hexokinase have activities that can be attributed to the C-terminal half and are
      similar in activity to chimeras composed of the C-terminal half of Type III and
      the intrinsically inactive N-terminal domain of Type I or the inactivated (by
      site-directed mutation) N-terminal half of Type II hexokinase. Virtually no
      activity was seen with chimeras constructed with the N-terminal half of the Type
      III isozyme and catalytically inactive (by site-directed mutation) C-terminal
      halves of Type I or Type II hexokinase. Substrate inhibition by Glc is seen only
      with the Type III isozyme and with chimeric forms containing the C-terminal half
      of Type III hexokinase and the N-terminal half of Type I or Type II isozyme, the
      latter inactivated by site-directed mutation; this is attributed to
      conformational changes induced by binding of Glc to a low affinity site in the N
      terminal half, with subsequent effect on catalytic activity of the C-terminal
      half. These results also provide further insight into the role of interactions
      (or lack of interactions) between the N- and C-terminal halves in the inhibition
      of the Type I-III isozymes by Glc-6-P, its antagonism by low concentrations of
      Pi, and the inhibition seen at higher concentrations of Pi.

PMID- 9028871
TI  - cAMP-dependent transactivation involving the homeodomain protein Pbx1.
AB  - Pbx1 is a DNA-binding homeodomain protein originally discovered in the t(1;19)
      chromosomal translocation associated with pediatric pre-B acute lymphoblastic
      leukemia. Previously we reported a cAMP-regulatory sequence (CRS1) in the
      promoter region of the bovine CYP17 gene encoding steroid 17alpha-hydroxylase
      cytochrome P450 (P450c17) to be the first endogenous Pbx1 binding site and that
      overexpression of Pbx1 in mouse adrenal Y1 tumor cells enhances cAMP-dependent
      transcription mediated by this element. Here we report further characterization
      of Pbx1 binding site in CRS1 and role of Pbx1 in cAMP-dependent, CRS1-mediated
      transcription. By gel shift analysis utilizing nuclear extracts from Y1 cells, a
      high-affinity Pbx-binding sequence has been determined to be TTGAT(T/G)GA(T/C)A
      which represents the 5' portion of CRS1. An artificial Pbx-binding sequence
      (PRS), previously determined by random PCR analysis, is similar to the Pbx1
      binding sequence in CRS1 and by both gel shift analysis and transfection studies
      shows characteristics very similar to CRS1. Upon overexpression, Pbx1 is found
      capable of enhancing CRS1-mediated transcription in both steroidogenic (Y1, JEG3)
      and nonsteroidogenic (HepG2 and S194) cells when coexpressed with the catalytic
      subunit of cAMP-dependent protein kinase A. Thus even though Pbx1 has been found
      to be involved only in cAMP-dependent transcription of a gene involved in
      steroidogenesis (CYP17), Pbx1 is capable of participating in cAMP-dependent
      transcription of target genes without complex formation with steroidogenic tissue
      specific nuclear factors.

PMID- 9028872
TI  - Heparinase-II-catalyzed degradation of N-propionylated heparin.
AB  - Currently there is great interest in the preparation of modified heparins and
      heparin-like polymers that possess specific and useful bioactivities. This paper
      demonstrates the potential of a particularly versatile endopolysaccharide lyase
      (heparinase II) as an analytical tool with which to assess both the chemical
      modification occurring during synthesis of such polymers and the actual primary
      structure of the final product of the enzyme activity. Additionally, the work
      widens our knowledge of the specificity range of this enzyme. The study involved
      a novel derivative of heparin containing the unnatural N-propionyl group, which
      was prepared from de-N-sulfated heparin. The extent of the chemical modification
      was followed throughout the preparation process by incubating samples with
      heparinase II and analyzing, with HPLC, the products of degradation catalyzed by
      the enzyme.

PMID- 9028873
TI  - A hot spot for hydrogen peroxide-induced damage in the human hypoxia-inducible
      factor 1 binding site of the PGK 1 gene.
AB  - Using ligation-mediated polymerase chain reaction to separately map the
      distribution of induced oxidized bases and strand breaks along the human PGK1
      promoter at nucleotide resolution, we previously described the pattern of
      oxidative DNA damage induced in vitro by Cu(II)/ascorbate/H2O2 [J. Biol. Chem.
      270, 17633-17640 (1995)]. Here we report that the pattern of in vivo base damage
      caused by H2O2 is almost identical to that of the previously used in vitro system
      with the exception of transcription factor-associated footprints. An unusually
      strong positive footprint for both strand breaks and oxidized bases is associated
      with binding of the hypoxia-inducible transcription factor-1. Base damage at this
      footprint was 52-91% repaired in 24 h, which was similar to the global base
      damage repair rate. However, strand breaks at this footprint were only 39-55%
      repaired in 24 h or approximately 100-fold slower than the global strand break
      repair rate.

PMID- 9028874
TI  - Mercuric salt-catalyzed removal of unsaturated glucuronic acid from
      chondroitinase-treated proteochondroitin sulfate.
AB  - Aggrecan (PG) was isolated from Swarm rat chondrosarcoma and the chondroitin 4
      sulfate removed with chondroitinase ABC (ABC) or ACII (AC), leaving a 4-deoxy
      beta-d-gluc-4-enuronosyl (DeltaGlcA) residue on the nonreducing terminus of the
      attached chondroitin sulfate chains. Mercuric acetate (as low as 5 mm) removed
      the DeltaGlcA from the PG-ABC within 10 min at 25 degrees C at pH 5.0, and the
      rate was pH independent between pH 3.0 and 5.0. The reaction was readily
      monitored by following the loss of reactivity to the monoclonal antibodies
      specific for 4-sulfated and nonsulfated unsaturated disaccharides in ELISA. After
      mercury treatment, there was a loss of carbazole-positive material and a decrease
      in the size of the linkage region oligosaccharides consistent with DeltaGlcA
      being removed. Aside from the loss of DeltaGlcA, neutral sugar composition and
      sialic acid content remained unchanged. After electrophoresis in a 4%
      polyacrylamide gel, Hg-treated PG-ABC and PG-AC migrated as single major bands,
      but with reduced mobilities, which is consistent with a loss of charge. There was
      a loss of reactivity to specific monoclonal antibodies. Treated aggrecan did not
      bind hyaluronic acid. This loss was not completely prevented by being present in
      a complex with link protein and hyaluronic acid. However, link protein could
      partially restore the hyaluronic acid interaction, so the effect of mercuric
      acetate on biological function will have to be assessed on an individual basis.
      Treatment with mercuric acetate is an effective, rapid, reproducible way of
      removing DeltaGlcA from both chondroitinase ABC and ACII-digested proteoglycan.

PMID- 9028875
TI  - Identification of positive and negative regulatory elements of the human
      cytochrome P4501A2 (CYP1A2) gene.
AB  - We previously demonstrated an enhancer-like positive regulatory element within a
      259-bp sequence (-2352 to -2094 bp) of the human CYP1A2 gene in HepG2 cells.
      Three protein binding sites were identified by DNase I footprinting analyses
      within the 259-bp sequence: protected region A PRA; -2283 to -2243 bp), PRB (
      2218 to -2187 bp), and PRC (-2124 to -2098 bp) (I. Chung and E. Bresnick, Mol.
      Pharmacol. 47, 677-685, 1995). In the present study, the functional significance
      of those protected regions was examined. Transfection experiments with deletion
      and substitution mutants defined the PRB and PRC as containing positive and
      negative regulatory elements, respectively. Human breast carcinoma MCF-7 cells
      were cotransfected with a hepatocyte nuclear factor-1 (HNF-1) expression vector
      and CYP1A2 promoter- or thymidine kinase promoter-luciferase reporter gene
      constructs. HNF-1, which contributes to the liver specificity of genes, enhanced
      reporter gene activity in a PRC sequence-dependent manner. These results
      suggested that PRC could exist bound to a repressor which was displaceable by
      other transcription factors such as HNF-1. Results obtained by transfection of
      HepG2 hepatoma cells with various PRB substitution mutant-luciferase gene fusion
      constructs indicated that the entire sequence of PRB was necessary for promoter
      activity. Consequently, the regulation of CYP1A2 expression is very complex,
      requiring a number of both positive and negative regulatory factors.

PMID- 9028876
TI  - Protein kinase CK2 down-regulates glucose-activated expression of the acetyl-CoA
      carboxylase gene.
AB  - It has been suggested that, in pancreatic beta-cells, acetyl-CoA carboxylase
      (ACC) is a key enzyme in glucose signal transduction leading to glucose-induced
      insulin secretion. The PII promoter is the only active promoter for the ACC gene
      in the beta-cell. Here we report that, in the pancreatic beta-cell, high glucose
      levels (above 20 mm) activate Sp1 binding to the glucose response element of the
      PII promoter, which leads to a dose-dependent increase in PII transcription. The
      expression of a gene coding protein kinase CK2 (CK2) alpha subunit, or the
      presence of okadaic acid (a serine/threonine protein phosphatase inhibitor),
      partially blocks the glucose activation of PII transcription. The inhibitory
      effect of CK2 alpha, or okadaic acid, was not observed in the absence of glucose
      or at low glucose concentrations. Phosphorylation of Sp1 by CK2 alpha leads to
      the inactivation of Sp1 binding to PII. Dephosphorylation of the phosphorylated
      Sp1 by protein phosphatase 1 (PP1) activates the binding of Sp1 to PII.
      Inhibition of PP1-catalyzed Sp1 dephosphorylation by okadaic acid, or PP1
      specific inhibitor 2, decreases Sp1 binding to PII. These results suggest that
      the phosphorylation/dephosphorylation of Sp1 by CK2/PP1 may be the underlying
      mechanism by which the expression of the PII promoter of ACC is controlled in the
      process of glucose-mediated insulin secretion in pancreatic beta-cells.

PMID- 9028877
TI  - Absorption of retinol from the retinol:retinol-binding protein complex by small
      intestinal gut sheets from the rat.
AB  - Absorption of retinol by the absorptive cells of the small intestine is a
      necessary first step in the metabolism of vitamin A. Previous studies had
      suggested that absorption of retinol from the retinol:retinol-binding protein
      complex (retinol:RBP) might be receptor mediated. We investigated the specificity
      of this process by determining the absorption of retinol from retinol:RBP by
      small intestinal sheets obtained from the suckling rat. We found that the
      absorption of retinol from retinol:RBP was a saturable process. Unlike the
      absorption of free retinol, absorption of retinol from retinol:RBP was not
      inhibited by N-ethylmaleimide. The absorption was specifically competable by
      unlabeled retinol:RBP and by both apo- and holocellular retinol-binding protein,
      but not by beta-lactoglobulin. This suggests that a specific mechanism is present
      for the absorption of retinol bound to RBP.

PMID- 9028878
TI  - A glycolytic enzyme binding domain on tubulin.
AB  - Cleavage of tubulin at tryptophan residues yielded several peptides, one of which
      strongly interacted with aldolase as determined by inhibition of aldolase
      activity. This peptide was identified as the C-terminal, residues 408-451, of the
      alpha-subunit of tubulin. Peptides with identical sequences to the C-terminal
      regions of the alpha- and beta-subunits of tubulin were synthesized to further
      characterize interactions with glycolytic enzymes. A 43-amino-acid C-terminal
      peptide from alpha-tubulin (residues 409-451) was found to have binding
      properties similar to those of native tubulin and was designated the tubulin
      glycolytic enzyme binding domain (T-GEBD-43mer).

PMID- 9028879
TI  - Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role
      of carotenoid-membrane incorporation and alpha-tocopherol.
AB  - beta-Carotene and other carotenoids are widely regarded as biological
      antioxidants. However, recent clinical trials indicate that beta-carotene
      supplements are not effective in disease prevention and raise questions about the
      biological significance of carotenoid antioxidant actions. To further explore
      this issue, we have reevaluated the antioxidant actions of beta-carotene in
      liposomal and biological membrane systems. In dilinoleoylphosphatidylcholine
      liposomes in which 0.35 mol % beta-carotene was incorporated into the bilayer
      during liposome preparation, the carotenoid inhibited lipid peroxidation
      initiated by 10 mm azobis[amidinopropane HCl] (AAPH). In carotenoid-free liposome
      suspensions to which the same amount of beta-carotene was added, no antioxidant
      effect was observed. Supplementation of rat liver microsomes with beta-carotene
      in vitro yielded microsomes containing 1.7 nmol beta-carotene mg-1 and 0.16 nmol
      alpha-tocopherol mg-1 microsomal protein. In beta-carotene supplemented
      microsomes incubated with 10 mm AAPH under an air atmosphere, lipid peroxidation
      did not occur until alpha-tocopherol was depleted by approximately 60%. beta
      Carotene exerted no apparent antioxidant effect and was not significantly
      depleted in the incubations. Similar results were obtained when the incubation
      was done at 3.8 torr O2. In liver microsomes from Mongolian gerbils fed beta
      carotene-supplemented diets, beta-carotene levels were 16-37% of alpha-tocopherol
      levels. The kinetics of AAPH-induced lipid peroxidation were no different in beta
      carotene-supplemented microsomes than in microsomes from unsupplemented animals,
      although the kinetics of beta-carotene and alpha-tocopherol depletion were
      similar. The results indicate that beta-carotene is ineffective as an antioxidant
      when added to preformed lipid bilayer membranes and that alpha-tocopherol is a
      much more effective membrane antioxidant than beta-carotene, regardless of the
      method of carotenoid-membrane incorporation. These results support a reevaluation
      of the proposed antioxidant role for beta-carotene in biological membranes.

PMID- 9028881
TI  - Rheology and Dynamics of Water-in-Oil Emulsions under Steady and Dynamic Shear
      Flow
AB  - The fundamental aspects governing the rheology of water-in-oil emulsions, such as
      viscosity ratio and morphology were considered. The model developed here is based
      on the early work of Pal and Rhodes (1989) for viscosity equation, combined with
      the theory of Lee and Park (1994) for the morphological contributions. Thus, the
      proposed conception enables us to predict not only the degree of flocculation but
      also viscosity ratio and morphological effects. The contribution of secondary
      morphology caused by the flocculation of droplets on the viscosity of dispersed
      emulsions has been found by using the factor, -alpha'q'xy/gamma; (where alpha' is
      the interfacial tension, q'xy is xy-component of anisotropy tensor, and gamma; is
      shear rate). However, this approach is only useful for system below the maximum
      random packing concentration. Experimentally, the bulk rheological properties
      have been examined under steady and dynamic shear flow to investigate the
      structure of emulsion. The flocculation-deflocculation transition was observed
      during the shear rate sweep, resulting in instant dilatancy of viscosity near the
      critical shear rate gamma; approximately 100 s-1.

PMID- 9028880
TI  - The Interaction Forces between Silica and Plasma-Treated Polypropylene Surfaces
      in Aqueous Solutions
AB  - The interaction forces between silica and plasma-treated polypropylene surfaces
      in aqueous NaCl solutions have been measured using a scanning force microscope.
      The measured interaction forces are well described by DLVO theory at large and
      moderate separation distances. However, at short range (<5 nm) an additional
      repulsive force is measured, presumably due to solvation of the surfaces. This
      additional force was not present when the interaction forces were measured
      between untreated polypropylene and silica under identical conditions. The
      presence of C-OH groups on the surface of the polypropylene is proposed to
      account for this additional repulsive force. In addition, the surface potential
      and charges fitted to the data were much higher than in the untreated
      polypropylene case. As no ionizable groups are present on either polypropylene
      surface, the adsorption of bicarbonate ion from solution is proposed to account
      for the surface charge.

PMID- 9028882
TI  - The Effect of Sodium Dodecyl Sulfate and M-alpha-Cyclodextrin on the Solubility
      and Partitioning of Xylenes in Aqueous Solutions
AB  - The solubility and the partitioning of p- and o-xylene in aqueous solutions
      containing M-alpha-CD, a partially methylated alpha-cyclodextrin, and the anionic
      surfactant sodium dodecyl sulfate (SDS) were studied by extraction experiments to
      evaluate the applicability of liquid membrane permeation for the separation of
      xylene isomeres. Experiments were carried out with the pure xylenes and 1:1
      mixtures of o- and p-xylene. The interactions of M-alpha-CD and SDS and their
      effects on the solubility and partitioning of xylenes were investigated. M-alpha
      CD was found to form 1:1 complexes with p- and o-xylene. Formation constants were
      determined as 141 M-1 for p-xylene and 48 M-1 for o-xylene, respectively, which
      are higher than those reported with nonmethylated alpha-CD. This can be explained
      by additional hydrophobic interactions with the methyl groups of the
      cyclodextrin. In contrast to the solubility in CD solutions, o-xylene was found
      to be more soluble than p-xylene in aqueous solutions of SDS. At constant
      concentrations of M-alpha-CD the addition of SDS led to the displacement of p
      xylene from the cyclodextrin cavity, which resulted in a decrease in its
      solubility. This decrease lasted until micelles were formed. Due to the
      solubilization of p-xylene in the micelles, further addition of SDS resulted in a
      linear increase in the solubility of p-xylene. However, at constant CD
      concentrations the solubility of o-xylene increased with the addition of SDS
      until about 5 mmol/liter SDS. This might be attributed to the formation of a
      ternary complex consisting of cyclodextrin, o-xylene, and SDS. At SDS
      concentrations greater than 5 mmol/liter, the solubility of o-xylene decreased,
      which was probably due to the formation of a more stable complex between SDS and
      M-alpha-CD. An addition of SDS beyond a critical concentration (CMC), where
      micelles are formed, resulted again in a linear increase of o-xylene solubility.
      The CMC was found to depend linearly on the concentration of M-alpha-CD in
      aqueous solution. Extraction experiments with a 1:1 mixture of o- and p-xylene
      showed that the two xylenes and SDS are in competition for M-alpha-CD. Since
      surfactants are always present when using emulsion liquid membranes and due to
      the complex interactions between SDS, the xylenes, and M-alpha-CD, no sufficient
      selectivity for the separation of the xylenes by liquid membrane permeation could
      be achieved.

PMID- 9028883
TI  - Use of Chemically Modified Silica with beta-Diketoamine Groups for Separation of
      alpha-Lactoalbumin from Bovine Milk Whey by Affinity Chromatography
AB  - Silica gel surface was chemically modified with beta-diketoamine groups by
      reacting the silanol from the silica surface with 3-aminopropyl-triethoxysilane
      and 3-bromopentanedione. With this material, copper ions were adsorbed from
      aqueous solutions. The chemical analysis of the silica-gel-immobilized
      acetylacetone provided a quantity of 0.67 mmol g-1 of organic groups attached to
      the support and 0.63 mmol g-1 of copper. This material was used as a stationary
      phase in IMAC (immobilized metal affinity chromatography), to separate alpha
      lactoalbumin from bovine milk whey. The results showed an efficient separation in
      the chromatographic column. The possibility of reutilization of the stationary
      phase was also investigated.

PMID- 9028884
TI  - Surface Tension Kinetics of the Wild Type and Four Synthetic Stability Mutants of
      T4 Phage Lysozyme at the Air-Water Interface
AB  - Surface tension kinetics exhibited by the wild type and selected stability
      mutants of T4 lysozyme at the air-water interface were monitored with DuNouy
      tensiometry. Mutant lysozymes were produced by substitution of the isoleucine at
      position 3 with cysteine, leucine, glycine, and tryptophan. Each substitution
      resulted in an altered structural stability quantified by a change in the free
      energy of unfolding. Surface pressure kinetics were compared to the kinetic model
      evolving from a simple model for protein adsorption. This model allowed for
      parallel, irreversible adsorption into two states directly from solution, where
      state 2 molecules were more tightly bound to the surface and occupied greater
      interfacial area than state 1 molecules. Moreover, the model allowed state 2
      molecules to increase spreading pressure more than state 1 molecules occupying
      the same interfacial area. The model indicated that less stable variants of T4
      lysozyme have a greater tendency to adsorb in state 2, and state 2 molecules
      increase spreading pressure more than state 1 molecules occupying the same
      interfacial area. While agreement between the model and experimental data was
      very good at low concentration, these results suggest that a more comprehensive
      two-state model should account for the influence of surface coverage on the
      adsorption rate constants.

PMID- 9028885
TI  - Microstructure-Confined Mechanical and Electric Properties of the
      Electrorheological Fluids under the Oscillatory Mechanical Field
AB  - The dynamic properties of two kinds of aluminosilicate-based electrorheological
      (ER) fluids were investigated under on-state and off-state electric fields. The
      dynamic responsive (frequency sweep spectrum and strain sweep spectrum)
      differences between these two ER suspensions were found under the off-state
      electric field, whereas similarities were observed once an external electric
      field was applied. Their dc conductances under an oscillatory mechanical field
      and their mechanical strengths under an oscillatory electric field were also
      examined. The periodically varied dc current in an oscillatory mechanical field
      and the decreased shear stress in an ac field were both found in these ER
      suspensions. The different in situ microstructures of these two ER fluids
      suggested on the basis of the percolation model, as well as their different
      response times measured experimentally, were presented to understand the
      experimental observations. Our results have a direct implication concerning the
      practical application of ER fluids.

PMID- 9028886
TI  - H-aggregation of Methyl Orange at the Interface between the Water Phase and Oil
      Phase in a Water-in-Oil Microemulsion
AB  - Methyl orange dissolved in a water-in-oil microemulsion was examined by UV-VIS
      absorption spectroscopy and differential scanning calorimetry (DSC). Methyl
      orange showed two temperature-dependent peaks at 416 and 354 nm in the
      microemulsion. The former was attributed to a methyl orange monomer, and the
      latter to aggregates of the dye in the parallel orientation (H-aggregates) at the
      interface between the water phase and the oil phase in the microemulsion. The
      position of methyl orange in the microemulsion was verified by DSC analysis.

PMID- 9028887
TI  - Polymer Dose Effects on Filtration Followed by Expression of Clay Slurries
AB  - Filtration followed by expression characteristics of cationic polymer conditioned
      clay slurries are reported for the first time in this work. As the polymer dosage
      increases, the resistance to filtration greatly decreases until a specific dose
      has been reached, where the zeta potential is close to zero. And further increase
      in polymer dose conversely raises the resistance. The expression data are
      interpreted by the Terzaghi-Voigt combined model, from which the model parameters
      are evaluated. The polymer conditioning has only a mild effect on the primary
      consolidation process but has, however, a considerable influence on secondary
      consolidation characteristics. When zeta potential changes from negative to
      positive, both the easiness of creeping of constituent particles within the
      sludge cake and the fraction of moisture removal by the secondary consolidation
      attain a maximum. The optimal polymer dose criterion considering the filtration
      and expression stages separately, or in combination, is

PMID- 9028888
TI  - Adsorption of Water Vapor by Homoionic Montmorillonites. Heats of Adsorption and
      Desorption
AB  - Adsorption isotherms for water vapor, basal spacing, and immersion heats and
      water desorption heats of Li+, Na+, Mg2+, Ca2+, Cu2+, and Fe3+ montmorillonite
      are measured at various relative humidities (r.h.). The amount of water adsorbed
      as a function of r.h. is found to increase gradually, whereas basal spacing
      increases and the adsorption heat decreases in steps. The water desorption heat
      also decreases in steps. The entropy of adsorbed water appears to be negative
      with respect to the entropy of liquid water. A theoretical model is proposed to
      describe the hydration process of Li+, Na+, Mg2+, Ca2+, Cu2+, and Fe3+
      montmorillonites. The experimental adsorption heats are found to have a direct
      relationship with the sum of the hydration energy of the cations plus expansion
      energy.

PMID- 9028889
TI  - Studies on Ferric Oxide Hydroxides
AB  - Adsorption of selenite (SeO2-3) on different polymorphic forms of iron
      oxyhydroxides and amorphous ferrihydrite was studied as a function of time,
      temperature, pH, and concentration of adsorbate(s) and adsorbent(s). Analysis of
      adsorption data indicates that the surfaces of all the forms of oxyhydroxides and
      ferrihydrite are heterogeneous in nature and that adsorption fits into a
      heterogeneous site binding model. The adsorption capacity of oxyhydroxides for
      SeO2-3 follows the order beta-FeOOH < alpha-FeOOH < gamma-FeOOH < delta-FeOOH <
      ferrihydrite.

PMID- 9028890
TI  - Hydrophobic Interactions between Dissimilar Surfaces
AB  - An atomic force microscope (AFM) was used to measure surface forces between a
      glass sphere and a silica plate. When the measurements were conducted between
      untreated surfaces, a "short-range" hydration force with decay lengths of 0.4 and
      3.0 nm was observed. When the surfaces were hydrophobized with
      octadecyltrichlorosilane (OTS), on the other hand, long-range hydrophobic forces
      with decay lengths in the range of 2-32 nm were observed. The force measurements
      were conducted between surfaces having similar and dissimilar hydrophobicities so
      that the results may be used for deriving an empirical combining rule. It was
      found that the power law force constants for asymmetric interactions are close to
      the geometric means of those for symmetric interactions. Thus, hydrophobic force
      constants can be combined in the same manner as the Hamaker constants. A plot of
      the power law force constants versus water contact angles suggests that the
      hydrophobic force is uniquely determined by contact angle. These results will be
      useful in predicting hydrophobic forces for asymmetric interactions and in
      estimating hydrophobic forces from contact angles.

PMID- 9028891
TI  - Interactions in the Thallium(I) Heptanoate and Heptanoic Acid System:
      Association, Aggregation, and Phase Behavior
AB  - The phase, association, and aggregation behavior of the binary system
      [TlO2C(CH2)5CH3 + HO2C(CH2)5CH3] have been investigated through temperature and
      enthalpy vs composition diagrams by determination of the thermal behavior of the
      pure components and 30 mixtures over an interval of nearly 300 K, and by
      differential scanning calorimetry and polarized microscopy. Total miscibility was
      observed in liquid and liquid crystalline phases but essentially total
      immiscibility among crystalline phases. The phase behavior exhibits: (1)
      Formation of two intermediate compounds which dissociate in the solid state at
      low temperature; (2) A eutectic reaction at salt molar fraction x = 0.08 about 3
      K below the acid melting point; (3) Unimolecular salt:acid association by very
      strong hydrogen bonding, which undergoes a crystal/crystal transition prior to
      incongruent melting at 295.5 K, occurring by a highly energetic peritectic
      reaction in which the compound evolves more than the sum of the total transition
      enthalpies of both components; (4) Lyotropic mesophase formation at 390.0 K over
      the x >/= 0.66 composition range by aggregation of a solid and a liquid phase to
      yield, on heating, a continuous series of liquid crystalline solutions with mixed
      lamellar structure and interlamellar spacings around 20 A as determined by powder
      X-ray diffractometry, their texture being focal conic, consistent with the neat
      thermotropic mesophase of the pure salt. A tridimensional phase diagram is
      presented. All these main reactions have been fully characterized by their
      nature, stoichiometry, and relevant thermodynamic data.

PMID- 9028892
TI  - Heterogeneous Nucleation of Naphthalene Vapor on Water Surface
AB  - The evaporation of a water drop into a ternary gaseous mixture of air, steam, and
      naphthalene vapor was investigated. The experimental results were compared with a
      theoretical prediction based on a numerical solution of coupled boundary layer
      equations for heat and mass transfer from a drop moving in ternary gas. In the
      experiments the naphthalene vapor condensed on the water drop as a supercooled
      liquid even at temperatures far below the melting point of naphthalene. The
      condensation on drop surface is discussed in terms of classical theory of
      heterogeneous nucleation on smooth surfaces.

PMID- 9028893
TI  - Effect of N-Cetylpyridinium Chloride on the Surface Free Energy of Leacril Fabric
AB  - Changes in the Lifshitz-van der Waals, gammaLWS, electron donor, gamma-S, and
      electron acceptor, gamma+S, surface free energy components of leacril fabric due
      to the adsorption of N-cetylpyridinium chloride (N-CP-Cl) were determined by the
      thin-layer wicking technique. It was found that the treatment of leacril with
      different amounts of N-CP-Cl practically does not change the value of the
      gammaLWS component. The treatments reduce the gamma+S component practically to
      zero, and a very sharp decrease of gamma-S (from 60.5 to 35.8 mJ/m2) was observed
      as the leacril was treated with increasing amounts of the above surfactant. It is
      concluded that the adsorption of N-CP-Cl on leacril takes place by means of
      electrostatic attractions between the quaternary ammonium group of N-CP and both
      the sulfonate and the sulfate groups of leacril. These groups could impart
      hydrophilicity to the surface of the leacril and hence acid-base interactions
      between the molecules of the surfactant and the surface of the fabric could
      explain the interactions between the N-CP-Cl and the leacril. The decrease in the
      gamma-S parameter in leacril fabric at concentrations of N-CP-Cl in solution as
      the fabric is treated is due to the decreasing content of sulfonate and sulfate
      groups electron donors, in the leacril due to acid-base neutralization between
      the cation of the surfactant and the surface groups of the fabric. The obtained
      value of gamma-S, 35.8 mJ/m2, after the treatment of leacril with 10(-2) M N-CP
      Cl could be due to the presence of N+-pyridinium groups, electron donors, on the
      leacril surface at the highest concentrations of surfactant due to the adsorption
      of the surfactant onto the leacril surface.

PMID- 9028894
TI  - The Synthesis of a New Class of Polymer Colloids with a Low Index of Refraction
AB  - In this paper we report the synthesis of highly charged polymer colloids based on
      the monomer dihydroperfluorobutylacrylate with a refraction index of nD20 = 1.37.
      By varying the polymerization parameters we could prepare polymer colloids in the
      size range of 70-500 nm. Removal of the excess ions in the suspensions leads to
      the formation of liquid-like or solid-like phases.

PMID- 9028896
TI  - Motion of a Colloidal Particle Coated with a Layer of Adsorbed Polymers in a
      Spherical Cavity
AB  - An analytical study is presented for the quasisteady translation and steady
      rotation of a spherical particle covered by a layer of adsorbed polymers located
      at the center of a spherical cavity that may also have an adsorbed polymer layer
      on its inside wall. The Reynolds number is assumed to be small, and the surface
      polymer layers are assumed to be thin with respect to the particle radius and the
      spacing between solid surfaces. To solve the Stokes flow equations within and
      outside the polymer layers a method of matched asymptotic expansions in small
      parameters lambda1 and lambda2 is used, where lambda1 and lambda2 are the ratios
      of the polymer-layer length scale to the radius of curvature at the particle
      surface and at the cavity wall, respectively. The results for the hydrodynamic
      force and torque exerted on the particle are expressed as an effective
      hydrodynamic thickness (L) of the adsorbed polymer layer surrounding the
      particle, which are accurate to O(lambda21). The O(lambda1) term for L normalized
      by its value in the absence of the cavity is found to be independent of the
      polymer segment distribution, the hydrodynamic interactions among the segments,
      and the volume fraction of the segments. The O(lambda21) term for L, however, is
      a sensitive function of the polymer segment distribution and the volume fraction
      of the segments. In general, the boundary effects on the motion of a polymer
      coated particle can be quite significant in appropriate situations.

PMID- 9028895
TI  - Microstructural and Magnetic Studies on Hydrothermally Prepared Hematite
AB  - Hematite particles of various shapes and sizes have been prepared hydrothermally
      at different pH values ranging from 3 to 10 from ferric chloride solution at
      180&deg;C. Particle size decreases with an increase in the pH of precipitation as
      observed from Transmission Electron Micrographs (TEM). A comparison of TEM and
      mean crystallite diameter (MCD) from XRD data reveals that the particles prepared
      are polycrystalline in nature. The polycrystallinity decreases with an increase
      in the pH of precipitation, and at pH 10 almost single crystalline nature of
      particles is obtained. Polycrystalline monodispersed pseudocubic particles
      obtained at pH 3 exhibit very high coercive force and remanent magnetization
      which decreases with an increase in pH, whereas Morin transition temperature, Tm,
      shows an opposite trend. Magnetic a.c. susceptibility increases with an increase
      in pH up to pH 7 and then decreases. A probable mechanism for the formation of
      polycrystalline particles has been suggested in order to explain the above trends
      in magnetic behavior.

PMID- 9028897
TI  - The Structure of Nonionic Micelles in Less Polar Solvents
AB  - Small angle neutron scattering, SANS, has been used to investigate the structure
      and geometry of nonionic micelles of monododecyl octaethylene glycol C12EO8,
      monododecyl hexaethylene glycol C12EO6, and monohexadecyl octaethylene glycol
      C16EO8 in less polar solvents: mixed solvents of water and glycerol, sorbitol,
      and ethylene glycol. For C12EO8 in glycerol/water solvent mixtures the addition
      of glycerol results in an increase in the micelle aggregation number and a
      decrease in the ethylene oxide (EO) headgroup hydration. The increase in micelle
      size is associated with the dehydration of the ethylene oxide headgroup and the
      consequent closer proximity of the lower consolute boundary. This follows from
      the observation that the same trends are seen at fixed glycerol content and
      increasing temperature where the intermicellar interactions become attractive.
      For C12EO6 micelles in water/ethylene glycol mixtures similar trends are
      observed, and the same conclusions may be drawn despite an increase in the
      clouding temperature. This can be explained by a greater dehydration of the
      solvent ethylene glycols such that the rate of change of solvent quality for the
      micelles with temperature is suppressed. A combination of SANS and Couette shear
      flow alignment has been used to investigate the structure of C16EO8 micelles in
      water/sorbitol and water/glycerol mixtures. The addition of sorbitol or glycerol
      results in less anisotropically shaped micelles. The resulting micelles are more
      labile, and show evidence of flexibility and shear induced transformations or
      extreme polydispersity. The temperature dependence of the micelle rod length of
      C16EO8/water/glycerol is similar to that previously observed for C16EO6 and
      C16EO8 micelles in water and for the mixed micelles of C16EO6/C16TAB.

PMID- 9028898
TI  - Preparation and Characterization of New Self-Assembled Polyamide Film Containing
      Disulfide Bonds on Gold Electrode
AB  - New polyamides containing disulfide bonds in their main chains are prepared by
      condensation between 3,3'-dithiodipropionic acid and various alkyldiamines (NH2
      (CH2)n-NH2, n = 4 and 12, polyamide I and II). The polyamides form a thin layer
      on a gold substrate. The surface of polyamide modified electrodes were
      investigated by AFM and XPS measurements. The surface structure depends on the
      polyamide structure, especially alkyl chain length of the polyamide. Furthermore,
      adsorption of ferrocene derivatives [1-ferrocenylmethanol (FME) or 2-amino-3
      ferrocenylpropionic acid (AFP)] on the polyamide modified electrodes and their
      electrochemical responses were investigated. Interaction between the polyamide on
      the electrode and the ferrocene derivatives depends on the structure of the
      ferrocene derivatives and polyamide chain length.

PMID- 9028899
TI  - Experimental and Theoretical Diffusivities of Cd and Sr in Hydrous Ferric Oxide
AB  - Oxides of manganese, aluminum, and especially iron are important sorbents for
      inorganic contaminants. The sorption process can be characterized by two steps.
      The first step is a rapid, reversible reaction between the bulk aqueous phase and
      external surfaces. The slow, second step is the rate limiting mechanism wherein
      the contaminant diffuses through small pores along surface sites. Isotherm and
      constant boundary condition studies were conducted to evaluate the sorption
      process. Best fit experimental surface diffusivities ranged from 10(-14) to 6 x
      10(-13) cm2/s. Using site activation theory and assuming a sinusoidal potential
      field along the pore surface, theoretical surface diffusion coefficients were
      estimated from the adsorption enthalpy.

PMID- 9028900
TI  - Characterization of the Interface between a Rough Metal and Smooth Mica in
      Contact
AB  - We introduce a technique to characterize, in situ, the solid-solid interface
      formed when a rough metal surface is placed in contact with a smooth mica
      surface. The technique is based on the use of extended spectral analysis of
      multiple beam interferometry in conjunction with the surface forces apparatus
      (SFA). The intensity versus wavelength spectra of light transmitted through the
      rough metal/mica interface is measured and compared to that transmitted through a
      smooth metal/mica interface. Interference theory is used to characterize the
      rough interface based on differences in the measured spectra. Roughness on the
      order of nanometers can be resolved. The key to our technique is the creation of
      a perfectly smooth metal/mica interface that is in all respects, except for
      roughness, identical to the metal/mica interface created in the SFA. We
      accomplish this by thermal evaporation of a metal film directly onto mica. We
      demonstrate the effectiveness of the technique by characterizing the structure of
      silver/mica and gold/mica interfaces. We also show how the technique can be used
      to investigate the exchange of fluids within the contact region.

PMID- 9028901
TI  - Sol-Gel Synthesis of Microporous Amorphous Silica from Purely Inorganic
      Precursors
AB  - Aqueous sodium silicate solutions and hydrochloric acid were used to prepare
      silica gels without any additives. In order to establish the optimum conditions
      for the preparation of microporous and monodisperse gels, the sol-gel reaction
      has been studied as a function of pH, concentration of silicate, time, and
      temperature. From 29Si NMR spectroscopy it was found that polycondensation sets
      on immediately after mixing the reagents, with a continuous increase of the
      fraction of 4-connected silicate tetrahedra (Q4) at the expense of Q1 and Q2.
      Polycondensation continues beyond the gelation point for 1 </= pH </= 7, but not
      for 7 </= pH </= 10. Two mechanisms were also observed for the gelation kinetics
      which is about second order with respect to [Si] for pH </= 7, whereas for pH >
      7, the order increases rapidly with pH. Gels formed at pH > 7 had an
      electrostatic nature and redissolved in water, whereas for pH </= 7, gelation was
      irreversible as expected for a gel where individual colloid particles are linked
      by chemical ( identical withSi-O-Si identical with) bonds. From nitrogen
      adsorption, it is found that the pore size depends mainly upon pH, the finest
      pores being obtained for pH 2-3 (BET surface area 650-700 m2/g, porosity 35%,
      pore radius 5-11 A).

PMID- 9028902
TI  - Scanning Force Microscopy Study of Methanol-Induced Changes in the Distribution
      of Silver Particles in Colloidal Metal Films
AB  - Colloidal silver particles were attached to a solid surface for use as a
      substrate for surface-enhanced Raman scattering and surface enhanced fluorescence
      spectroscopies. The enhancement of Raman scattering is dramatically increased
      after exposure of the substrates to methanol solution. Scanning force microscopy
      was used to visualize the substrate before and after the methanol treatment, and
      a statistical evaluation of the particle distribution revealed some differences.
      The nearest-neighbor distance was decreased after the exposure to methanol. This
      effect suggests that an aggregation of the particles occurred. This aggregation
      is probably based on increased attractive interactions and lateral mobility of
      the particles in methanol.

PMID- 9028903
TI  - XAFS and Bond-Valence Determination of the Structures and Compositions of Surface
      Functional Groups and Pb(II) and Co(II) Sorption Products on Single-Crystal alpha
      Al2O3
AB  - The structures and compositions of Pb(II) adsorption complexes and surface
      binding sites on alpha-Al2O3 (0001) and (1&1macr;02) surfaces were investigated
      in the presence of water using grazing-incidence X-ray absorption fine structure
      (GI-XAFS) spectroscopy. Pb(II) ions were found to adsorb in an inner-sphere mode
      on alpha-Al2O3 (1&1macr;02) but as outer-sphere complexes on alpha-Al2O3 (0001).
      The distance between the outer-sphere complexes and the surface places useful
      constraints on double-layer properties of water. A bond-valence model is
      described that relates the reactivities of surface functional groups and
      adsorption complexes to their molecular structures and compositions, and places
      constraints on the stoichiometries of adsorption reactions, including proton
      release. The EXAFS and modeling results suggest that Pb(II) and Co(II) ions bond
      to [AlAlAl-->O-1/2--> and [Al-OH+1/22] surface functional groups. In contrast,
      [AlAl > OH] groups complex Co(II) but not Pb(II). The results indicate the
      importance of using structurally defined surface sites to describe reactions at
      oxide-water interfaces.

PMID- 9028904
TI  - Freundlich's Isotherm Extended by Statistical Mechanics
AB  - In this paper we obtain an asymptotic development compatible with Freundlich's
      isotherm, theta = KCm. That expression was derived underlying the theory of
      heterogeneous surface. We assume the distribution function of adsorption sites to
      be in the exponential form and the sites to follow the Langmuir energy
      homogeneous isotherm. The derived expression represents an analytical solution to
      the fundamental integral equation for the overall adsorption isotherm in its
      correct integration limit. From this expression we clearly identify the
      parameters K and m, the Freundlich parameters. We applied this expression to fit
      the experimental data for the adsorption of CO2 into BPL-activated carbon.

PMID- 9028905
TI  - Boundary Effects on Electrophoretic Motion of Spherical Particles for Thick
      Double Layers and Low Zeta Potential
AB  - The electrophoretic motion of a charged sphere in the presence of a rigid
      boundary is analyzed for low surface zeta potentials but arbitrary kappaa, where
      a is the particle radius and kappa is the inverse Debye length. The boundary
      configurations considered are a single flat wall, a slit, and a long cylindrical
      tube. Using a method of reflections, we obtain the particle velocity for a
      constant applied electric field in powers of lambda up to O(lambda6), where
      lambda is the ratio of the particle radius to the distance from the boundary.
      This analysis is valid as long as the double layer around the particle does not
      overlap significantly with the double layer at the boundary. The effect of finite
      kappaa is to enhance the viscous retardation of the particle, although for large
      separations the first effect due to the proximity of the boundary is still at
      O(lambda3) in all cases. When the applied field is parallel to the boundary, the
      electrophoretic velocity is not proportional to the difference in zeta potential
      between the particle and the boundary (as occurs for kappaa --> infinity), and
      the proximity of the boundary may increase the particle velocity or change its
      direction. An important result of the analysis is that the hindrance to the
      electrophoretic velocity of a particle in a cylindrical pore increases
      significantly as kappaa is reduced below 10.

PMID- 9028906
TI  - Creaming and Flocculation of Oil-in-Water Emulsions Containing Sodium Caseinate
AB  - The influence of protein content on the stability of concentrated oil-in-water
      emulsions (35 or 45 vol% oil, droplet diameter approximately 0.5 &mgr;m, pH 6.8)
      containing sodium caseinate as the sole emulsifying agent has been investigated.
      Time-dependent creaming profiles were determined at 30&deg;C using an ultrasound
      velocity scanning technique with data analysis based on a Urick equation
      renormalization technique. The results indicate that creaming kinetics has a
      complex dependence on caseinate content. At low protein content (1 wt%),
      corresponding to less than half that required for saturation monolayer coverage,
      the emulsion is destabilized by bridging flocculation (accompanied by some
      coalescence). At higher protein content (2 wt%), where individual droplets are
      fully protected against protein bridging or coalescence by the thick adsorbed
      protein layer, the unflocculated emulsion has good stability over a period of
      several weeks. With further increase of protein content (>/=3 wt%), the observed
      creaming stability is reduced again, with the rate of serum separation at the
      bottom of the sample now greatly increased. This is attributed here to depletion
      flocculation by unadsorbed caseinate, probably in the form of small particles
      called "casein submicelles." Light microscopy has confirmed that the visually
      observable extent of reversible depletion flocculation in concentrated emulsions
      of this type is very sensitive to overall protein content. Once the caseinate
      concentration reaches a high value (6 wt%), the strength of the depletion
      interaction is such that it produces a very strong emulsion droplet network which
      can reorganize only slowly, and is hence much more stable to creaming and serum
      separation.

PMID- 9028907
TI  - The Critical Coagulation Concentration of Counterions: Spherical Particles in
      Asymmetric Electrolyte Solutions
AB  - The ratio of the critical coagulation concentration (CCC) of counterions is
      evaluated for spherical particles and asymmetric electrolytes. A perturbation
      method is adopted to solve the Poisson-Boltzmann equation governing the
      electrical potential distribution of the system under consideration. On the basis
      of the result obtained, an approximate expression for the CCC is derived. Another
      approach based on the Derjaguin approximation is also used to estimate the CCC.
      We show that the CCC ratio of counterions is a complicated function of the
      valences of the ion species in the liquid phase and the sizes of particles.
      Depending upon the thickness of the Debye length, the CCC ratio of counterions
      for various combinations of electrolytes can be estimated. The classic Schulze
      Hardy rule for planar particles in a symmetric electrolyte solution can be
      recovered as a limiting case of the present model. If the surface potential is
      low, the effect of curvature on the CCC ratio of counterions is negligible.

PMID- 9028908
TI  - The Adsorption of Poly(vinyl alcohol) to Biodegradable Microparticles Studied by
      X-Ray Photoelectron Spectroscopy (XPS)
AB  - The design of biodegradable microparticle drug delivery systems with precisely
      tailored surface properties requires surface analytical methods that can relate
      polymer chemistry and fabrication parameters to the final surface chemistry of
      the microparticles. We demonstrate using X-ray photoelectron spectroscopy (XPS)
      that it is possible to identify significant variations in the surface chemistry
      of microparticles composed of poly(lactic acid) (PLA), poly(lactide-co-glycolide)
      (PLGA), or block copolymers of PLA or PLGA with poly(ethylene glycol) (PEG).
      These variations are related to the mechanism by which the microparticle/water
      interface is stabilized. This, in turn, is controlled by the interfacial surface
      tensions of the polymers within aqueous environments. For PEG containing block
      copolymers, adsorption of a surfactant, poly(vinyl alcohol) (PVA), from the
      aqueous medium onto the polymer is reduced compared with the PLA and PLGA
      polymers. This reduction is achieved because the PEG segments, within the
      copolymer structure, stabilize the polymer/water interface. Estimates of the
      relative amounts of lactide, lactide-co-glycolide, vinyl alcohol, and ethylene
      glycol monomer units at the microparticle surfaces are presented based on curve
      fitting analysis of the XPS data.

PMID- 9028909
TI  - NOTE
AB  - The influence of different counterions (F-, Cl-, Br-, I-) on the electric surface
      properties ("permanent" dipole moment and electric polarizability) of beta-FeOOH
      ellipsoid particles in dilute aqueous dispersions is studied by electric light
      scattering method and electrophoresis. An additional longitudinal permanent
      dipole moment appears with the increase of ionic strength for all added
      counterions, but is most pronounced in the case of I- ions. The additional
      orientation moment is most likely due to the distortion of the counterions'
      distribution close to the particle surface.

PMID- 9028910
TI  - NOTE
AB  - Atomic force microscopy was used to investigate the mixed monolayer of FC- and HC
      amphiphiles. Clear topographic images showing domain structure of the mixed
      monolayer and the data of the domain size have been provided. It is revealed that
      in the mixed monolayer the sodium octadecanesulfonate molecules construct the
      hexagonal domain dispersing in the continuous two-dimensional phase of
      perfluorononanoic acid. These results strongly support that, due to the mutual
      phobicity between fluorocarbon chain and hydrocarbon chain, there exists phase
      separation in the mixed monolayer of fluorocarbon and hydrocarbon amphiphiles,
      albeit the pi-A curves would obey the simple additive rule.

PMID- 9028911
TI  - NOTE
AB  - 2H NMR quadrupolar splittings of clay suspensions monitor the orientation of
      water molecules near the solid surface. Two limiting water interfacial sites
      explain our results on montmorillonite, hectorite, and saponite suspensions. The
      location of cation isomorphous substitution and the Ca2+/Na+ molar ratio of
      exchangeable cations modulate their relative importance. With beidellite
      suspensions, water orientation at the clay surface cannot be described within the
      above scheme.

PMID- 9028912
TI  - High survival rate of one-cell mouse embryos cooled rapidly to -196 degrees C
      after exposure to a propylene glycol-dimethylsulfoxide-sucrose solution.
AB  - We investigated the effect of duration of exposure at 22 degrees C to a solution
      containing dimethylsulfoxide (Me2SO), propylene glycol (PROH), and sucrose on the
      survival rate of one-cell mouse embryos cooled rapidly to -196 degrees C. The
      cryoprotectant solutions were made up on a molar basis and six different times of
      exposure were tested (1, 2.5, 5, 10, 15, and 20 min). After rapid thawing and
      dilution in a 1 M sucrose solution the survival rate was calculated as the number
      of hatching or hatched blastocysts formed per frozen-thawed and recovered one
      cell embryo. We demonstrated that the optimum time of exposure depends on the
      type of cryoprotectant solution used. The optimum time of exposure was 1 min when
      a 4.5 M PROH-0.25 M sucrose solution was used, 2.5 min when a 2.25 M PROH-2.25 M
      Me2SO-0.25 M sucrose solution was used, and 5 min when a 4.5 M Me2SO-0.25 M
      sucrose solution was used. For prolonged exposure times beyond the optimum,
      survival rates were the highest when solutions containing 2.25 M PROH-2.25 M
      Me2SO-0.25 M sucrose were used. To identify factors that may influence the
      survival rates, we carried out further experiments on one-cell embryos in the
      different cryoprotectant solutions. We evaluated (i) the survival rates after
      exposure without freezing and (ii) the volume changes during exposure. It is
      suggested that the optimum time of exposure to a cryoprotectant solution depends
      on cryoprotectant permeation and that detrimental effects after prolonged
      exposure are a consequence of chemical toxicity. When one-cell mouse embryos were
      exposed for 3 min to a solution containing 2.25 M PROH-2.25 M Me2SO-0.25 M
      sucrose before rapid cooling to -196 degrees C, 98% of the zygotes were
      morphologically intact after rapid thawing. There was no further loss in
      viability during in vitro culture on after transfer in vivo as compared to
      unfrozen control embryos.

PMID- 9028913
TI  - Freeze drying of cardiac valves in preparation for cellular repopulation.
AB  - When freeze-dried cardiac valves have been implanted they remained acellular.
      This study is the initial step in the development of a method designed to
      repopulate the substance of the freeze-dried valve with fibroblasts and the
      lumenal surface with endothelial cells. In this scheme, the freeze-drying process
      performs three functions; it provides a porous matrix, it kills the donor cells,
      and it preserves the collagen structure and hence the mechanical strength of the
      valve. This paper describes the production of appropriate porosity in freeze
      dried porcine pulmonary valve leaflets. We found that Tg' for this material is 
      83 degrees C, which made it impracticable to freeze-dry exclusively from the
      glassy state. Uncontrolled freeze-drying produced a variable structure with most
      of the pores considerably smaller than the desired size and a dense layer,
      apparently devoid of perforations, on the surface. Compacted layers also occurred
      within the substance of the leaflets. These appearances suggested that extensive
      collapse had occurred during the drying process. Variation of the cooling rate,
      the primary drying temperature, and the warming rate during secondary drying
      enabled us to identify the following conditions that provided satisfactory
      internal porosity: cooling at 5 degrees C/min, vacuum drying for 6 h at -20
      degrees C, and secondary drying for 10 h during rewarming at 0.06-0.08 degrees
      C/min. The internal cavities measured 100-350 microns2 by ca. 400 microns2, which
      is adequate to provide access for the fibroblasts (cross-sectional area ca. 150
      200 microns2 when rounded but fusiform when attached. However, the internal
      porous structure rarely communicated with the surface and mechanical perforation
      was required to provide continuity between the surface and the internal sponge.
      The resulting method provides a basis for studies of cell colonization.

PMID- 9028914
TI  - The influence of cryopreservation on murine oocyte water permeability and
      osmotically inactive volume.
AB  - Osmotic experiments were performed on unfrozen (N = 18) and cryopreserved (N =
      21) ICR murine oocytes in order to determine whether a standard cryopreservation
      process alters membrane water permeability (hydraulic conductivity, Lp) and/or
      osmotically inactive volume (Vb). Oocytes, initially in an isotonic (288 mOsm)
      NaCl solution, were exposed to 900 mOsm NaCl in a microdiffusion chamber. Cell
      size changes were videotaped and analyzed using a parameter estimation program.
      Best estimates for a two-parameter model (Lp and Vb) which includes the
      osmotically inactive volume as a fitting parameter are presented for the first
      time. The cryopreservation process produced no significant difference between the
      mean Lp or the mean Vb values for the unfrozen control population (Lp = 0.64 +/-
      0.15 micron/min/atm, Vb = 24.7 +/- 2.9%) and the cryopreserved population (Lp =
      0.63 +/- 0.12 micron/min/atm, Vb = 28.0 +/- 10.8%). While the cryopreservation
      process did not cause significant changes in the mean values of Lp, Vb, or the
      variability of Lp, it did produce more variability of Vb. The cause of the
      increased variability of Vb produced by cryopreservation is unknown. These
      results suggest that the osmotic properties of unfrozen control oocytes can be
      used as a reasonable approximation for frozen-thawed oocytes. They also suggest
      that multiple parameter models and parameter estimation methods may be useful in
      developing a more comprehensive understanding of the more subtle alterations in
      osmotic properties that were detected here. Statistical tests were also used for
      the first time to confirm the assumption that all of the experimental populations
      were derived from normal distributions.

PMID- 9028915
TI  - Cryopreservation of mature bovine oocytes following centrifugation treatment.
AB  - In vitro matured bovine oocytes were frozen slowly in 1.6 M 1,2-propanediol
      following centrifugation treatment for polarization of lipid droplets in the
      cytoplasm. After thawing, the survival of the oocytes was assessed
      morphologically and also by in vitro fertilization and culture. The polarization
      of cytoplasmic lipid droplets had a negative effect on the survival of frozen
      thawed oocytes. Thus, this treatment did not improve the frequency of normal
      fertilization and development to blastocysts, compared with that of frozen
      control oocytes. However, the frequency of polyspermy and activation of lipid
      polarized oocytes that survived after freezing-thawing and subsequent in vitro
      fertilization tended to be less than those of surviving control oocytes. In
      addition, the effect of centrifugation treatment was to produce a small but
      significant increase in the cleavage rate of oocytes that survived after freezing
      thawing and the development rates to blastocysts of surviving lipid-polarized
      oocytes tended to increase, compared with those of surviving control oocytes.
      These results suggest that the freezing tolerance of the spindle and other
      organelles of in vitro matured bovine oocytes is associated with lipid droplets
      and may be improved by the polarization of cytoplasmic lipid droplets before
      cryopreservation.

PMID- 9028916
TI  - Cryosurgery of dunning AT-1 rat prostate tumor: thermal, biophysical, and
      viability response at the cellular and tissue level.
AB  - This study investigates cryodestruction of the Dunning AT-1 rat prostate tumor at
      the single cell, tissue slice, and in vivo levels. The thermal history around a 3
      mm-diameter cylindrical cryosurgical probe was predicted by solving the bioheat
      equation in a one-dimensional cylindrical geometry. At various radial positions
      in the iceball this thermal history was approximated by a constant cooling rate
      and a final, steady-state temperature (or end-temperature). The predicted cooling
      rates and end temperatures ranged from > or = 1000 degrees C/min to 5 degrees
      C/min and -196 degrees C to -20 degrees C, respectively. These cooling rates and
      end-temperatures were then imposed on single AT-1 cells, AT-1 tissue slices in
      vitro and AT-1 tumors in vivo. The single cells and tissue slices were frozen by
      LN2 immersion, copper block slam-freezing, or controlled cooling on a
      cryomicroscope or a directional solidification stage. LN2 immersion is lethal to
      AT-1 cells (presumably due to intracellular ice formation), while cooling at 5
      100 degrees C/min leaves some viable cells (at end-temperatures ranging between 
      20 and -40 degrees C). AT-1 tumor slices show extensive intracellular ice
      formation due to slam cooling, extensive dehydration at 100 degrees C/min, and
      total dehydration at rates < or = 10 degrees C/min to end temperatures below -10
      degrees C. Postfreeze culture and histology of the AT-1 tissue show that
      extensive intracellular ice formation is lethal, while cellular dehydration and
      vascular engorgement leave viable cells (at end-temperatures between -20 and -40
      degrees C). Based solely on the single cell and in vitro tissue damage achieved
      by cooling rates and end-temperatures, a sizable portion of a cryosurgically
      frozen tumor would be expected to survive. However, in vivo cryosurgery performed
      on AT-1 tumors demonstrated that the tissue was damaged throughout the
      cryolesion, even at the periphery where the thermal history would be expected to
      allow single cells and tissue slices to survive in vitro. Taken together, these
      results suggest that damage mechanisms other than those due to cooling rate and
      end-temperature may be responsible for the increased cellular destruction at the
      periphery of the iceball in vivo and that cooling rate is less important than end
      temperature in determining cryosurgical damage in AT-1 tumors. Experiments are
      ongoing to determine if the time held at an end temperature, thawing rate,
      vascular response, or other mechanisms are primarily responsible for the enhanced
      destructive capability in vivo.

PMID- 9028917
TI  - Temperature Regulation of Supercooling and Gut Nucleation in Relation to Diapause
      of Pyrrhocoris apterus (L.) (Heteroptera)
AB  - The heteropteran Pyrrhocoris apterus (L.) does not survive freezing of its body
      fluids; there is a good correlation between values of survival at subzero
      temperatures and the supercooling point (SCP), i.e., the temperature at which
      body fluids start to freeze. The decrease of the SCP and thus the increase in
      cold hardiness is regulated by photoperiod and temperature. The relative
      importance of these factors depends on the physiological state of the insect. The
      SCP is about -7&deg;C at the onset of prediapause and a decrease of about 4
      5&deg;C is associated with the development of the diapause syndrome in adults;
      these processes both are induced by a short-day photoperiod with temperature
      playing a secondary role. The induction of the diapause syndrome is a
      prerequisite for the subsequent decrease of the SCP by about 5-6&deg;C during
      cold acclimation. An intermediate temperature of 15&deg;C, or fluctuating outdoor
      temperatures and short-day photoperiods, are more suitable for the decrease of
      SCP than 5&deg;C in continuous darkness. The sensitivity to photoperiod gradually
      disappears during the development of diapause; after the termination of diapause
      around the winter solstice the SCP irreversibly increases at a high temperature
      of 26&deg;C even if exposed to a short-day photoperiod. The SCPs of hemolymph,
      gut, fat body, and gonads were compared to whole-body SCP. The gut was identified
      as the primary site of ice nucleation because its SCP value was very similar to
      the value for the whole body in both short-day and long-day insects. The SCPs of
      other organs, including the hemolymph, were always lower than the whole body SCP.
      Food was not a source of ice nucleating agents because the SCP of freshly ecdysed
      adults remained high after 2 weeks of starvation. In contrast, feeding was a
      prerequisite for the decrease of the SCP during prediapause. In postdiapause
      insects, the SCP increased at high temperatures in spite of the absence of food.

PMID- 9028918
TI  - Rectal protection during prostate cryosurgery: design and characterization of an
      insulating probe.
AB  - This study presents the design and characterization of an insulating probe made
      of silicone that could be used for enhancing the safety and efficacy of prostate
      cryosurgery. The probe would be placed in Denonvilliers' fascia between the
      prostate and the rectum prior to freezing. During freezing, the iceball would be
      monitored by ultrasound through the silicone, and direct temperature monitoring
      of the rectal and prostatic tissue via thermocouples mounted on opposing sides of
      the device. Both theoretical and experimental studies were performed to verify
      the insulating and acoustic properties of the probe. The insulating effect of the
      silicone will enhance cell death within the prostate while minimizing tissue
      freezing injury and therefore fistula formation postfreeze in the rectum.
      Experiments were also performed with the insulator placed in gelatine which
      showed that the silicone material is transparent to ultrasound. In addition the
      silicone was itself visible under ultrasound imaging, a characteristic which may
      assist in the delivery of the device to the surgical site. One possible scenario
      for reconfiguration and delivery of the device is suggested prior to a
      cryosurgery. The success of this device in insulating and monitoring temperature
      during freezing suggests that it can also be useful in protecting sensitive
      tissues adjacent to a surgical site when extreme heat is applied (i.e., electron
      or hyperthermic surgery).

PMID- 9028919
TI  - Mechanisms of evolutionary changes in timing, spatial expression, and mRNA
      processing in the msp130 gene in a direct-developing sea urchin, Heliocidaris
      erythrogramma.
AB  - Developmental processes associated with skeletogenesis differ in the direct
      developing sea urchin Heliocidaris erythrogramma from that in Heliocidaris
      tuberculata and other indirect-developing species. In H. erythrogramma, the
      differences include ingression of a much higher number of mesenchyme cells,
      failure of the cells to form the typical ring pattern of cells prior to the onset
      of skeletogenesis, a significantly reduced larval skeleton, and a delay in timing
      of expression of the skeletogenic cell-restricted gene msp130. We report that the
      heterochronic change in msp130 expression is regulated at the level of
      transcription. By transient expression of reporter constructs containing msp130
      promoter regions from direct- and indirect-developing species, we found that this
      evolutionary change in regulation is consistent with changes in the timing of
      action of trans-acting factors in skeletogenic mesenchyme cells. We further used
      these experiments to show that the H. erythrogramma promoter contains elements
      required for correct spatial expression in the primary mesenchyme cells of an
      indirect-developing host. We finally show that alternate processing of H.
      erythrogramma msp130 is thus far specific to this species and not an aspect of
      adult skeletogenesis.

PMID- 9028921
TI  - Establishment of a cell line from Spodoptera litura (Lepidoptera: Noctuidae) and
      replication of S. litura nuclear polyhedrosis virus in vitro.
AB  - A new cell line, designated IBL-SLO1A, was established from pupal ovaries of the
      tobacco cutworm Spodoptera litura. Cells were grown in the TNM-FH insect cell
      culture medium supplemented with 10% fetal bovine serum. The subculture of cells
      was initiated with 1-3 x 10(5) cells/ml, a split ratio about 1:10. The growth
      curve of the cells fit the model of exponential growth (Y = e-0.6750 + 0.0317X R2
      = 0. 98), the population doubling time during logarithmic growth at 28 degrees C
      was 21.9 hr. The number of chromosomes was about 140. Cytopathology
      characteristics of baculovirus infection were observed when the culture cells
      were infected with SINPV derived from alkali dissolution of occlusion bodies at
      24 hr postinfection (pi). The cells lysed and released occlusion bodies into
      culture medium at 120 hr pi.

PMID- 9028922
TI  - A new small RNA virus persistently infecting an established cell line of Galleria
      mellonella, induced by a heterologous infection.
AB  - A persistent infection in a Galleria mellonella cell line was revealed when
      infected with a maize stem borer picorna-like virus isolated on Sesamia cretica
      (MSBV). The new virus, completely different from the MSBV, is designated as G.
      mellonella cell line virus (GmclV), induces spectacular cytopathic effects, and
      is also considered efficient in vivo. The GmclV is a 29-nm-diameter isometric
      virus, with single-strand RNA of 2.9 x 10(6) Da molecular weight with a poly(A)
      tract. Its capsid is constituted of only two major polypeptides, of 34,500 and
      32,500 Da, and no minor bands could be detected. The characteristics of the GmclV
      do not permit us to classify it with assurance. Even though it has not yet been
      identified as a picornavirus, it can be classified in the small RNA virus group
      of the Picornaviridae. G. mellonella represents a very interesting model, owing
      to the fact that two different persistent viruses belonging to the same family
      were isolated in vivo and in vitro, to further the understanding of the general
      phenomenon of persistency and induction.

PMID- 9028923
TI  - Encapsulation response of Ciona intestinalis (Ascidiacea) to intratunical
      erythrocyte injection.
AB  - Electron microscopic studies on the encapsulation induced by erythrocyte
      injection into the tunic of the ascidian Ciona intestinalis were carried out. The
      observations reported in the present paper complete the description previously
      given of capsule architecture and contribute to the characterization of the cells
      involved in the inflammatory reaction. The inflamed area is surrounded by an
      ample and peculiar "three-layered coat" respectively composed of flattened and
      packed extratunical hemocytes, the monolayered epithelium, and a layer of
      intratunical electron-dense particles. The latter are also clustered, variously
      arranged, and distributed in the tunic ground substance. The epithelial cells
      appear to be undergoing an active secretory phase; in several regions they also
      show discontinuities and organule and surface changes. The infiltrating
      hemocytes, mainly globular and unilocular granulocytes, appear frequently to be
      degranulating and in relation with electron-dense particles, net-like fibrous
      materials, and fine membranes. The involvement of morula-shaped granulocytes is
      discussed, as well as possible relationships with the melanization process, and
      finally analogies in the structural organization with the inflammatory reactions
      induced in other invertebrates. A schematic drawing, based on all available
      observations of the capsule architecture, is presented in order to reconstruct
      the entire inflamed area and illustrate the relative fine features.

PMID- 9028924
TI  - A 16S rRNA gene oligonucleotide probe for identification of Bacillus
      thuringiensis isolates from sheep fleece.
AB  - Larvae of the Australian sheep blowfly Lucilia cuprina are susceptible to some
      strains of Bacillus thuringiensis, including some isolates from sheep fleeces
      from South Australia and Western Australia. Larvicidal strains of B.
      thuringiensis include var. thuringiensis, tolworthi, darmstadiensis, morrisoni,
      and toumanoffi. As part of an ecological study, a large number of B.
      thuringiensis fleece isolates from untreated sheep and sheep previously treated
      with larvicidal B. thuringiensis were screened for larvicidal activity. A
      ribotyping method to distinguish larvicidal B. thuringiensis jetted (sprayed)
      onto sheep from the natural B. thuringiensis flora of the fleece was developed. A
      cloned fragment of the 16S rRNA gene used as a probe for B. thuringiensis DNA
      digested with restriction endonucleases enables separation of B. thuringiensis
      serovars and separation within the serovars thuringiensis, tolworthi, and
      kurstaki. The 16S gene probe method is useful for distinguishing between
      reisolates of larvicidal B. thuringiensis jetted onto sheep and the background B.
      thuringiensis population present prior to jetting.

PMID- 9028925
TI  - Attachment of Metarhizium anisopliae to the southern green stink bug Nezara
      viridula cuticle and fungistatic effect of cuticular lipids and aldehydes.
AB  - In this paper we examined the conidial attachment of Metarhizium anisopliae on
      the southern green stink bug, Nezara viridula, using the exuvia and nymphal stage
      of the host as a substrate for M. anisopliae conidiospores. Initial studies using
      fluorescein isothiocyanate (FITC)-labeled conidia examined the differential
      binding of conidia to various sites on the cuticle. Both the topography and the
      chemistry of the cuticle affected conidial adhesion. Conidia were trapped in
      areas containing large numbers of setae (e.g., antennal tips, apical portions of
      tibia and tarsi). Chemical treatments to remove the cuticle proteins did not
      affect conidial adhesion, but solvent extraction of cuticular lipids
      significantly reduced the adhesion of M. anisopliae spores. Germination of M.
      anisopliae conidia attached to N. viridula cuticle was much less than conidia
      attached to other insect cuticle substrates. After a 24-hr incubation, only 5-20%
      of the conidia produced detectable germ tubes. The aldehyde (E)-2-decenal, a
      primary component of the stink bug scent gland, was detected in cuticle extracts
      and found to be selectively fungistatic to certain entomopathogenic fungi,
      including M. anisopliae. The hydrocarbon fraction (nC13 and nC21 to nC31
      hydrocarbon series) served as a binding substrate for M. anisopliae, but conidia
      did not degrade these hydrocarbons and did not use them as a carbon source.

PMID- 9028926
TI  - Replication of Anticarsia gemmatalis nuclear polyhedrosis virus in four
      lepidopteran cell lines.
AB  - Anticarsia gemmatalis nuclear polyhedrosis virus (AgNPV; family Baculoviridae) is
      pathogenic for larvae of the velvetbean caterpillar, Anticarsia gemmatalis Hubner
      an important pest of soybean. AgNPV is a viable alternative to chemical control
      of A. gemmatalis in Brazil, where its use as a pesticide has brought significant
      economic and environmental benefits. Although a significant amount of information
      is available on the ecological and biological control aspects of AgNPV, very
      little is known about the replication cycle and host specificity of this virus.
      We examined the susceptibility of four lepidopteran cell lines to AgNPV.
      Infections of the A. gemmatalis UFL-AG-286 cell line were highly productive.
      Ninety percent of infected cells had polyhedral inclusion bodies by 48 hr after
      infection, and the infectious virus titer was 10(8) IU/ml. Viral DNA replication
      was efficient, and the maximal rate of synthesis was between 6 and 12 hr after
      infection. Infections of the Spodoptera frugiperda IPLB-SF-21 cell line were
      productive but less efficient. Infections of Choristoneura fumiferana IPRI-CF
      124T cells with this virus were poor, with only 5% of the cells forming polyhedra
      and an infectious virus titer of 10(6) IU/ml. The level of viral DNA replication
      was low, suggesting that this system was predominantly abortive. Infections of
      Bombyx mori BM-5 cell lines were abortive, and cells had apoptosis-like
      morphology. No polyhedra or increase in infectious levels were observed, and
      there was little or no replication of viral DNA. Our data suggest that
      restriction of AgNPV replication in abortive cell lines is due mainly to
      inability of viral DNA to replicate efficiently. The possible causes of low DNA
      replication are discussed. Our results suggest that the cell lines utilized in
      this study can provide an important model for studying mechanisms of AgNPV host
      specificity.

PMID- 9028927
TI  - Effects of diet-age and streptomycin on virulence of Autographa californica M
      nucleopolyhedrovirus against the tobacco budworm.
AB  - Addition of the antibiotic streptomycin to two artificial diets routinely used in
      bioassays of neonate lar vae of Heliothis virescens (tobacco budworm) infected
      with Autographa californica M nucleopolyhedrovirus (AcMNPV) increased lethal
      times of the virus. After storage of diets for 3 weeks at 4 degrees C, lethal
      times of infected larvae were significantly slower compared to those for larvae
      bioassayed using diets stored for 2 weeks or less. The effect of diet-age on rate
      of mortality was not the result of a change in total protein content or pH of the
      diet, but was apparently the result of some other alteration in the quality of
      the diet (e.g. microbial spoilage, palatibility, and/or nutritional value
      unrelated to total protein). Although we did not determine why lethal times were
      slower in response to streptomycin concentration or diet-age, we did find that
      slower lethal times were correlated with slower relative growth rates (RGR) of
      infected larvae. In addition, RGR of infected larvae decreased as a function of
      increasing streptomycin concentration, diet-age, and the interaction of the two
      factors. These results demonstrate that it is difficult to obtain consistent and
      comparable bioassay results if antibiotic composition and diet-age are not
      controlled. We suggest a standardized diet or highly standardized procedures for
      a given diet be developed that permits comparison of bioassays among and within
      laboratories.

PMID- 9028928
TI  - Morphological characterization of the hemocytes of the clam, Ruditapes decussatus
      (Mollusca: Bivalvia).
AB  - Hemocytes play an important role in internal defence in molluscs. The morphology
      of hemolymph cells was studied for the first time in Ruditapes decussatus. Two
      main types of hemocytes (hyalinocytes and granulocytes) exist in R. decussatus.
      Three types of granulocytes were identified by light microscopy, in accordance
      with the presence of basophilic or acidophilic granules or a mixture of both in
      the cytoplasm. The existence of hyalinocytes and granulocytes was confirmed by
      electron microscopy. Some monoclonal antibodies (MABs) raised against hemocytes
      of Crassostrea gigas showed cross-reactivity with the total population of
      hemocytes of R. decussatus; however, none of the MABs raised against hemocytes of
      Mytilus edulis showed cross-reactivity. The MABs assayed did not allow us to
      distinguish hemocyte subpopulations.

PMID- 9028929
TI  - Effect of azadirachtin A on the fine structure of the midgut of Rhodnius
      prolixus.
AB  - Rhodnius prolixus fed with azadirachtin A showed significant changes in the
      ultrastructural organization of the epithelial cells of the stomach and the
      intestine. Changes included (a) clustering of the microvilli, (b) disorganization
      of the extracellular membrane layers, (c) modifications in the array of
      spherocytes, and (d) disorganization of the basal portion of the epithelial
      cells. We suggest that these changes interfere significantly with the intestinal
      environment, making it unsuitable for survival and multiplication of the
      protozoan Trypanosoma cruzi.

PMID- 9028930
TI  - The effect of humidity on germination and infection of termites by the
      hyphomycete, Metarhizium anisopliae.
AB  - The effect of relative humidities (r.h.) from 90 to 100% on germination of a
      termite-active isolate of Metarhizium anisopliae (isolate FI25 and FI610) was
      studied using a liquid germinating medium to which the appropriate amount of
      glycerol had been added. Germination was increasingly delayed at water activities
      equivalent to 99, 98, and 96% r.h. and completely inhibited at 94, 92, and 90%.
      Twenty-one isolates were then screened for germination at 96 and 100% r.h. All
      isolates showed delayed germination at 96% r.h. but most isolates eventually gave
      a high final percentage germination at this humidity. Two isolates, FI527 and
      FI638, were markedly slower to germinate at both humidities. The susceptibility
      of two species of termites, Nasutitermes exitiosus and Coptotermes acinaciformis,
      to FI610 was tested at r.h. down to 86%-the lowest humidity at which the insects
      would survive. No consistent effect of humidity on pathogenicity was detected.
      Mortality occurred over the range range of humidities tested; sporulation from
      the disease-killed termites, however, occurred only at r.h. above 93%. It is
      concluded that the microclimate around living termites is usually sufficiently
      humid to ensure infection under most field conditions and that humidity is
      unlikely to limit the efficacy of the fungus in controlling termites.

PMID- 9028931
TI  - Inactivation of conidia of Paecilomyces fumosoroseus by near-ultraviolet (UVB and
      UVA) and visible radiation.
AB  - The detrimental effects of solar radiation, especially the ultraviolet waveband,
      on quiescent conidia of Paecilomyces fumosoroseus were investigated. Conidia were
      irradiated by a high-intensity source, which emitted a continuous spectrum from
      270 to 1100 nm and which was equipped with long-pass filters to block short
      wavelengths below 280, 295, 320, or 400 nm. After irradiation, conidia were
      tested for germinability, survival, and infectivity toward Spodoptera frugiperda
      larvae. It was demonstrated that the detrimental effects of light depended on
      irradiance in the shortest wavelengths. The UVB (280-320 and 295-320 nm) appeared
      to be the most detrimental part of natural radiation, although UVA (320-400 nm)
      was also harmful. Visible and near infrared radiations were less harmful than UV.
      Our results demonstrate that the irradiance of the UVB waveband should be
      considered as the pertinent factor for the detrimental effects of sunlight on the
      persistence of conidia of entomopathogenic fungi in insolated environments.

PMID- 9028932
TI  - Instar susceptibility of the monarch butterfly (Danaus plexippus) to the
      neogregarine parasite, Ophryocystis elektroscirrha.
AB  - The susceptibility of the monarch butterfly (Danaus plexippus) larvae to the
      neogregarine parasite, Ophryocystis elektroscirrha, was tested in the laboratory.
      Spore loads recovered from infected monarch butterflies were directly related to
      the inoculum level, larval stage of the host, and spore age. There was a linear
      relationship between spores ingested by first instar larvae and spore
      concentration. Larvae feeding on leaves treated with 0, 50, 500, 5000, or 50,000
      spores averaged 0, 0, 193, 457, or 1,255 spores, respectively, on the abdomens of
      the adult butterflies. When first, third, and fifth instar larvae were given 14.5
      spores/mg of body weight, there was no significant difference in the spore load
      of the adults resulting from the first and third instars. However, there were
      significant differences in the spore load from adults resulting from the first
      and third instars versus the fifth instar. In addition, 1-year-old spores were
      not as infectious as fresh spores. Our findings indicate that under field
      conditions, the first instar is most likely to become infected because one spore
      appears sufficient to produce a detectable spore load in the adult. Older instars
      are less susceptible and have fewer opportunities to encounter sufficient viable
      spores for infection to occur. Thus, vertical transmission appears to be the
      primary mode of parasite maintenance in natural populations of monarch
      butterflies.

PMID- 9028933
TI  - Pathophysiologic implications of membrane phospholipid asymmetry in blood cells.

PMID- 9028934
TI  - Use of leukemic dendritic cells for the generation of antileukemic cellular
      cytotoxicity against Philadelphia chromosome-positive chronic myelogenous
      leukemia.
AB  - The success of adoptive immunotherapy for the treatment of leukemia depends on
      the generation of T cells that can specifically react with malignant cells.
      Dendritic cells (DCs) are important antigen-presenting cells in the development
      of antileukemic T-cell responses. In this study, we generated DCs from peripheral
      blood cells of patients with chronic myelogenous leukemia (CML). CML cells
      incubated concurrently with granulocyte-macrophage colony-stimulating factor,
      interleukin-4, and tumor necrosis factor-alpha in vitro developed morphologic and
      phenotypic characteristics of DCs. Fluorescence in situ hybridization showed the
      presence of t(9;22) in the nuclei of these cells, indicating that they were
      leukemic in origin. These cells were potent stimulators of lymphocyte
      proliferation in specific in vitro assays for DC function. Autologous T cells
      stimulated with in vitro-generated, leukemic DCs displayed vigorous cytotoxic
      activity against CML cells but low reactivity to major histocompatability complex
      matched normal bone marrow cells. Cytotoxic activity against CML targets was
      fourfold to sixfold higher using DC-stimulated autologous T cells than with
      autologous T cells expanded by culture with interleukin-2 alone. DC-stimulated T
      cells also inhibited growth of CML clonogenic precursors in colony-forming assays
      in vitro. These results suggest that cytokine-driven in vitro differentiation of
      CML cells results in generation of DCs with potent T-cell stimulatory function.
      In vitro-generated DCs can be effectively used as antigen-presenting cells for
      the ex vivo expansion of antileukemic T cells.

PMID- 9028935
TI  - Case-control study suggests a favorable impact of TEL rearrangement in patients
      with B-lineage acute lymphoblastic leukemia treated with antimetabolite-based
      therapy: a Pediatric Oncology Group study.
AB  - TEL gene rearrangement is the most common genetic lesion in pediatric acute
      lymphoblastic leukemia (ALL), occurring in about 25% of B-lineage cases. We
      previously showed that, among patients treated on St Jude protocols, TEL
      rearrangement independently conferred an excellent prognosis. To extend these
      results to patients treated with antimetabolite-based therapy, we performed
      Southern blot analysis to determine the TEL gene status of 104 cases of B-lineage
      ALL treated on Pediatric Oncology Group 8602, matched on age, gender, and
      leukocyte count. There were 52 failures among the 77 patients with germline TEL,
      compared with only 8 failures among 27 patients in the rearranged group. Based on
      a two-sided logistic regression analysis, stratified for age (subdivided at 10
      years), leukocyte count (subdivided at 50,000), and gender, the estimated odds of
      failing by 4 years in the germline TEL group is 5.4 times that of the rearranged
      TEL group, with 95% confidence from 1.9 to 15.6, two-sided P = .0009. Thus, the
      presence of a rearranged TEL gene is also associated with an improved survival
      among patients treated with antimetabolite-based therapy. Our results indicate
      that all newly diagnosed ALL patients should be screened for TEL gene
      rearrangements and suggest that these patients are candidates for less intensive
      therapy.

PMID- 9028936
TI  - Interleukin-10 inhibits spontaneous colony-forming unit-granulocyte-macrophage
      growth from human peripheral blood mononuclear cells by suppression of endogenous
      granulocyte-macrophage colony-stimulating factor release.
AB  - Spontaneous growth of myeloid colonies (colony-forming unit-granulocyte
      macrophage [CFU-GM]) can be observed in methylcellulose cultures containing
      peripheral blood mononuclear cells (PB-MNCs) and is supposedly caused by the
      release of colony-stimulating factors (CSF) by accessory cells. Because of its
      cytokine synthesis-inhibiting effects on T lymphocytes and monocytes, interleukin
      10 (IL-10) may be a potential candidate for indirect modulation of hematopoiesis.
      We studied the effect of recombinant human IL-10 (rhIL-10) on spontaneous growth
      of myeloid colonies derived from human PB-MNCs. A total of 10 ng/mL of IL-10
      almost completely inhibited spontaneous CFU-GM proliferation (by 95.1%; P < .001,
      n = 7) in unseparated PB-MNCs. This effect was dose-dependent and specific,
      because a neutralizing anti-IL-10 antibody was able to prevent IL-10-induced
      suppression of CFU-GM growth. Spontaneous CFU-GM growth, which required the
      presence of both monocytes (CD14+ cells) and T lymphocytes (CD3+ cells), was also
      greatly suppressed by a neutralizing anti-granulocyte-macrophage CSF (GM-CSF)
      antibody but was only slightly or not at all inhibited by antibodies against G
      CSF or IL-3. Moreover, IL-10-suppressed colony growth could be completely
      restored by the addition of exogenous GM-CSF. Using semiquantitative polymerase
      chain reaction, we were able to show that GM-CSF transcripts that spontaneously
      increased in PB-MNCs within 48 hours of culture were markedly reduced by the
      addition of IL-10. Inhibiton of GM-CSF production in PB-MNCs by IL-10 was also
      confirmed at the protein level by measuring GM-CSF levels in suspension cultures.
      Our findings suggest that autonomous CFU-GM growth, resulting from an interaction
      of monocytes and T lymphocytes, is mainly caused by endogenous GM-CSF release and
      can be profoundly suppressed by the addition of exogenous IL-10. Considering the
      strong inhibitory action of IL-10 on GM-CSF production and spontaneous cell
      growth in vitro, this cytokine may be useful in myeloid malignancies in which
      autocrine and/or paracrine mechanisms involving GM-CSF are likely to play a
      pathogenetic role.

PMID- 9028937
TI  - Initiation of murine embryonic erythropoiesis: a spatial analysis.
AB  - Hematopoiesis in the mouse conceptus begins in the visceral yolk (VYS), with
      primitive erythroblasts first evident in blood islands at the headfold stage
      (E8.0). VYS erythropoiesis is decreased or abrogated by targeted disruption of
      the hematopoietic transcription factors tal-1, rbtn2, GATA-1, and GATA-2. To
      better understand the potential roles of these genes, and to trace the initial
      temporal and spatial development of mammalian embryonic hematopoiesis, we
      examined their expression patterns, and that of betaH1-globin, in normal mouse
      conceptuses by means of in situ hybridization. Attention was focused on the 36
      hour period from mid-primitive streak to early somite stages (E7.25 to E8.5),
      when the conceptus undergoes rapid morphologic changes with formation of the yolk
      sac and blood islands. Each of these genes was expressed in extraembryonic
      mesoderm, from which blood islands are derived. This VYS expression occurred in a
      defined temporal sequence: tal-1 and rbtn2 transcripts were detected earlier than
      the others, followed by GATA-2 and GATA-1, and then by betaH1-globin. Transcripts
      for all of these genes were present in VYS mesoderm cell masses at the neural
      plate stage (E7.5), indicating commitment of these cells to the erythroid lineage
      before the appearance of morphologically recognizable erythroblasts. By early
      somite stages (E8.5), GATA-2 mRNA expression is downregulated in VYS blood
      islands as terminal primitive erythroid differentiation proceeds. We conclude
      that primitive mammalian erythropoiesis arises during gastrulation through the
      ordered temporal expression of tal-1, rbtn2, GATA2, and GATA-1 in a subset of
      extraembryonic mesoderm cells. During the stages analyzed, tal-1 and rbtn2
      expression was also present in posterior embryonic mesoderm, while GATA-1 and
      GATA-2 expression was evident in extraembryonic tissues of ectodermal origin.

PMID- 9028938
TI  - Augmented production of interleukin-6 by normal human osteoblasts in response to
      CD34+ hematopoietic bone marrow cells in vitro.
AB  - Based on anatomic and developmental findings characterizing hematopoietic cells
      in close approximation with endosteal cells, we have begun an analysis of
      osteoblast/hematopoietic cell interactions. We explore here the functional
      interdependence between these two cell types from the standpoint of de novo
      cytokine secretion. We determined that, over a 96-hour period, CD34+ bone marrow
      cells had no significant effect on osteoblast secretion of granulocyte colony
      stimulating factor, granulocyte-macrophage colony-stimulating factor, or
      transforming growth factor-beta1, but in some experiments minor increases in
      leukemia inhibitory factor levels were observed. However, when CD34+ bone marrow
      cells were cocultured in direct contact with osteoblasts, a 222% +/- 55% (range,
      153% to 288%) augmentation in interleukin-6 (IL-6) synthesis was observed. The
      accumulation of IL-6 protein was most rapid during the initial 24-hour period,
      accounting for nearly 55% of the total IL-6 produced by osteoblasts in the
      absence of blood cells and 77% of the total in the presence of the CD34+ cells.
      Cell-to-cell contact does not appear to be required for this activity, as
      determined by coculturing the two cell types separated by porous micromembranes.
      The identity of the soluble activity produced by the CD34+ cells remains unknown,
      but is not likely due to IL-1beta or tumor necrosis factor-alpha, as determined
      with neutralizing antibodies. To our knowledge, these data represent the first
      demonstration that early hematopoietic cells induce the production of molecules
      required for the function of normal bone marrow microenvironments, in this case
      through the induction of hematopoietic cytokine (IL-6) secretion by osteoblasts.

PMID- 9028939
TI  - Impaired hematopoiesis in paroxysmal nocturnal hemoglobinuria/aplastic anemia is
      not associated with a selective proliferative defect in the
      glycosylphosphatidylinositol-anchored protein-deficient clone.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) results from somatic mutations in the
      PIG-A gene, leading to poor presentation of glycosylphosphatidylinositol (GPI)
      anchored surface proteins. PNH frequently occurs in association with suppressed
      hematopoiesis, including frank aplastic anemia (AA). The relationship between GPI
      anchored protein expression and bone marrow (BM) failure is unknown. To assess
      the hematopoietic defect in PNH, the numbers of CD34+ cells, committed
      progenitors (primary colony-forming cells [CFCs]), and long-term culture
      initiating cells (LTC-ICs; a stem cell surrogate) were measured in BM and
      peripheral blood (PB) of patients with PNH/AA syndrome or patients with
      predominantly hemolytic PNH. LTC-IC numbers were extrapolated from secondary CFC
      numbers after 5 weeks of culture, and clonogenicity of LTC-ICs was determined by
      limiting dilution assays. When compared with normal volunteers (n = 13), PNH
      patients (n = 14) showed a 4.7-fold decrease in CD34+ cells and an 8.2-fold
      decrease in CFCs. LTC-ICs in BM and in PB were decreased 7.3-fold and 50-fold,
      respectively. Purified CD34+ cells from PNH patients had markedly lower
      clonogenicity in both primary colony cultures and in the LTC-IC assays. As
      expected, GPI-anchored proteins were decreased on PB cells of PNH patients. On
      average, 23% of monocytes were deficient in CD14, and 47% of granulocytes and 58%
      of platelets lacked CD16 and CD55, respectively. In PNH BM, 27% of CD34+ cells
      showed abnormal GPI-anchored protein expression when assessed by CD59 expression.
      To directly measure the colony-forming ability of GPI-anchored protein-deficient
      CD34+ cells, we separated CD34+ cells from PNH patients for the GPI+ and GPI
      phenotype; CD59 expression was chosen as a marker of the PNH phenotype based on
      high and homogeneous expression on fluorescent staining. CD34+ CD59+ and CD34+
      CD59-cells from PNH/AA patients showed similarly impaired primary and secondary
      clonogeneic efficiency. The progeny derived from CD34+ CD59- cells were both CD59
      and CD55-. A very small population of CD34+ CD59- cells was also detected in
      some normal volunteers; after sorting, these CD34+ CD59- cells formed normal
      numbers of colonies, but their progeny showed lower CD59 levels. Our results are
      consistent with the existence of PIG-A-deficient clones in some normal
      individuals. In PNH/AA, progenitor and stem cells are decreased in number and
      function, but the proliferation in vitro is affected similarly in GPI-protein
      deficient clones and in phenotypically normal cells. As measured in the in vitro
      assays, expansion of PIG-A- clones appears not be caused by an intrinsic growth
      advantage of cells with the PNH phenotype.

PMID- 9028940
TI  - Cell-cycle-dependent regulation of erythropoietin receptor gene.
AB  - To understand the regulatory mechanism of erythropoietin (EPO) receptor (EPOR)
      gene expression, the effect of EPO on the steady-state level of EPOR mRNA was
      examined using the human EPO-dependent cell line UT-7 as a model system. We found
      that the treatment of UT-7 cells with EPO resulted in a transient decrease of the
      EPOR mRNA level. This transient downregulation was also induced by stimulation
      with granulocyte-macrophage colony-stimulating factor (GM-CSF), another
      stimulator of UT-7 cell growth. These results raised the possibility that EPOR
      gene expression is in part related to cell growth. Moreover, it was found that
      EPO-induced downregulation of EPOR mRNA level was preceded by a transient
      downregulation of GATA-1 mRNA. To examine the relationship between the expression
      of EPOR, GATA-1, and GATA-2 mRNA levels and the cell cycle, logarithmically
      growing UT-7 cells were centrifugically fractionated according to the cell-cycle
      phase. Both EPOR and GATA-1 mRNA levels, but not the GATA-2 mRNA level,
      concomitantly decreased at the G0/G1 phase and increased at the S and G2/M
      phases. An electrophoretic mobility shift assay (EMSA) showed that in EPO
      stimulated UT-7 cells, the dynamic changes in EPOR gene expression paralleled the
      GATA-1 DNA-binding activity to the oligonucleotide probe containing a GATA
      binding site located at the promoter region of the EPOR gene. These findings
      suggest that the regulation of EPOR mRNA level is mainly associated with GATA-1
      gene expression in UT-7 cells undergoing proliferation, and that these serial
      events are under the control of, or related to, the cell cycle.

PMID- 9028941
TI  - Cycling status of CD34+ cells mobilized into peripheral blood of healthy donors
      by recombinant human granulocyte colony-stimulating factor.
AB  - In this study, we assessed the functional and kinetic characteristics of highly
      purified hematopoietic CD34+ cells from the apheresis products of 16 normal
      donors undergoing glycosylated granulocyte colony-stimulating factor (G-CSF)
      treatment for peripheral blood stem cells (PBSC) mobilization and transplantation
      in allogeneic recipients. Mobilized CD34+ cells were evaluated for their colony
      forming capacity and trilineage proliferative response to selected recombinant
      human (rh) CSF in vitro and the content of very primitive long-term culture
      initiating cells (LTC-IC). In addition, the cycling status of circulating CD34+
      cells, including committed clonogenic progenitor cells and the more immature LTC
      IC, was determined by the cytosine arabinoside (Ara-C) suicide test and the
      acridine orange flow cytometric technique. By comparison, bone marrow (BM) CD34+
      cells from the same individuals were studied under steady-state conditions and
      during G-CSF administration. Clonogenic assays in methylcellulose showed the same
      frequency of colony-forming unit cells (CFU-C) when PB-primed CD34+ cells and BM
      cells were stimulated with phytohemagglutinin-lymphocyte-conditioned medium (PHA
      LCM). However, mobilized CD34+ cells were significantly more responsive than
      their steady-state BM counterparts to interleukin-3 (IL-3) and stem cell factor
      (SCF) combined with G-CSF or IL-3 in presence of erythropoietin (Epo). In
      cultures added with SCF, IL-3, and Epo, we found a mean increase of 1.5- +/- 1
      fold (standard error of the mean [SEM]) of PB CFU-granulocyte-macrophage and
      erythroid progenitors (burst-forming units-erythroid) as compared with BM CD34+
      cells (P < .05). Conversely, circulating and BM megakaryocyte precursors (CFU
      megakaryocyte) showed the same clonogenic efficiency in response to IL-3,
      granulocyte-macrophage-CSF and IL-3, IL-6, and Epo. After 5 weeks of liquid
      culture supported by the engineered murine stromal cell line M2-10B4 to produce G
      CSF and IL-3, we reported 48.2 +/- 35 (SEM) and 62.5 +/- 54 (SEM) LTC-IC per
      10(4) CD34+ cells in PB and steady-state BM, respectively (P = not significant).
      The Ara-C suicide assay showed that 4% +/- 5% (standard deviation [SD]) of
      committed precursors and 1% +/- 3% (SEM) of LTC-IC in PB are in S-phase as
      compared with 25.5% +/- 12% (SD) and 21% +/- 8% (SEM) of baseline BM,
      respectively (P < .001). However, longer incubation with Ara-C (16 to 18 hours),
      in the presence of SCF, IL-3 and G-CSF, or IL-6, showed that more than 60% of LTC
      IC are actually cycling, with no difference being found with BM cells.
      Furthermore, studies of cell-cycle distribution on PB and BM CD34+ cells
      confirmed the low number of circulating progenitor cells in S- and G2M-phase,
      whereas simultaneous DNA/RNA analysis showed that the majority of PB CD34+ cells
      are not quiescent (ie, in G0-phase), being in G1-phase with a significant
      difference with baseline and G-CSF-treated BM (80% +/- 5% [SEM] v 61.9% +/- 6%
      [SEM] and 48% +/- 4% [SEM], respectively; P < .05). Moreover, G-CSF
      administration prevented apoptosis in a small but significant proportion of
      mobilized CD34+ cells. Thus, our results indicate that mobilized and BM CD34+
      cells can be considered equivalent for the frequency of both committed and more
      immature hematopoietic progenitor cells, although they show different kinetic and
      functional profiles. In contrast with previous reports, we found that PB CD34+
      cells, including very primitive LTC-IC, are cycling and ready to progress into S
      phase under CSF stimulation. This finding should be taken into account for a
      better understanding of PBSC transplantation.

PMID- 9028942
TI  - Characterization of cis-acting sequences and trans-acting signals regulating
      early growth response 1 and c-fos promoters through the granulocyte-macrophage
      colony-stimulating factor receptor in BA/F3 cells.
AB  - Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) activates a set
      of genes such as c-fos, jun, myc, and early growth response gene 1 (egr-1).
      Studies on BA/F3 cells that express hGM-CSF receptor (hGMR) showed that two
      different signaling pathways controlled by distinct regions within the beta
      subunit are involved in activation of c-fos/c-jun genes and in c-myc,
      respectively. However, the region(s) of the beta subunit responsible for
      activation of the egr-1 gene and other regulatory genes has not been identified.
      We describe here how egr-1 promoter is activated by hGMR through two regions of
      the beta subunit, with these regions being required for activation of the c-fos
      promoter. Coexpression of dominant negative (dn) Ras (N17ras) or dn JAK2 almost
      completely suppressed the activation of egr-1 and c-fos promoters. Deletion
      analysis of egr-1 promoter showed two cis-acting regions responsible for
      activation by hGM-CSF or mouse interleukin-3 (mIL-3), one between nucleotide
      positions (nt) -56 and -116, and the other between nt -235 and -480, which
      contains tandem repeats of the serum response element (SRE) sites. Similar
      experiments with the c-fos promoter showed that cis-acting regions containing the
      SRE/AP-1 sites is sufficient for activation by hGM-CSF. Based on these
      observations, we propose that signaling pathways activating egr-1 and c-fos
      promoters are controlled by SRE elements, either through the same or overlapping
      pathways that involve JAK2 and Ras.

PMID- 9028943
TI  - Thrombopoietin enhances proliferation and differentiation of murine yolk sac
      erythroid progenitors.
AB  - Thrombopoietin (TPO), the ligand for the receptor proto-oncogene c-Mpl, has been
      cloned and shown to be the critical regulator of proliferation and
      differentiation of megakaryocytic lineage. Initially, TPO was not considered to
      have the activity on hematopoietic lineages other than megakaryocytes. Recently,
      however, TPO was reported to enhance the in vitro erythroid colony formation from
      human bone marrow (BM) CD34+ progenitors or from mouse BM cells in combination
      with other cytokines. We examined the effects of TPO on the colony formation of
      hematopoietic progenitors in mouse yolk sac. TPO remarkably enhanced
      proliferation and differentiation of erythroid-lineage cells in the presence of
      erythropoietin (Epo). This effect was observed even in the absence of Epo.
      Compared with adult BM, yolk sac turned out to have relatively abundant erythroid
      and erythro-megakaryocytic progenitors, which responded to TPO and Epo
      stimulation. TPO similarly stimulated erythroid colony formation from in vitro
      differentiation-induced mouse embryonic stem (ES) cells whose hematopoietic
      differentiation status was similar to that of yolk sac. These findings help to
      understand the biology of hematopoietic progenitors of the early phase of
      hematopoiesis. Yolk sac cells or in vitro differentiation-induced ES cells would
      be good sources to analyze the TPO function on erythropoiesis.

PMID- 9028944
TI  - Impaired steel factor responsiveness differentially affects the detection and
      long-term maintenance of fetal liver hematopoietic stem cells in vivo.
AB  - The results of previous studies have shown that the development of hematopoiesis
      during fetal life can occur in the absence of Steel factor (SF) signaling. On the
      other hand, impairment of this mechanism can severely compromise the ability of
      cells from adult bone marrow to regenerate hematopoiesis on their transplantation
      into myeloablated recipients. This apparent paradox could result from changes
      during ontogeny in the responsiveness of hematopoietic stem cells to regulators
      that may substitute for SF as well as from differences in the availability of
      such factors during embryogenesis and in the myeloablated adult. To investigate
      these possibilities, we studied the effect of W41 and W42 mutations on the
      numbers, phenotype, and posttransplant self-renewal behavior of primitive
      hematopoietic cells present in the fetal liver (FL) of 14.5-day-old mouse
      embryos. In W41/ W41 FL, day-12 spleen colony-forming units and long-term culture
      initiating cells appeared both quantitatively and qualitatively similar to their
      counterparts in the FL of +/+ embryos. W41/W41 FL also contained near normal
      numbers (approximately 50% of controls) of transplantable lymphomyeloid stem
      cells with competitive reconstituting ability in myeloablated adult +/+
      recipients (as assessed for up to at least 16 weeks posttransplant). Moreover,
      both the original phenotype of these W41/W41 competitive repopulating units
      (CRUs) and their clonal posttransplant output of mature progeny were normal.
      Similarly, when myeloablated adult +/+ mice were cotransplanted with 5 x 10(4)
      +/+ FL cells and a sevenfold to 70-fold excess of W41/W41 FL CRUs, the
      contribution of the +/+ FL CRUs to the circulating white blood cell count present
      5 weeks later was markedly reduced as compared with that of mice that received
      only +/+ FL cells. However, over the next 3 months, the proportion of mature
      white blood cells that were derived from +/+ precursors increased significantly
      (P < .002) in all groups (to > or = 30%), indicating that the ability to sustain
      hematopoiesis beyond 5 weeks is more SF-dependent than the ability to initially
      reconstitute both lymphoid and myeloid compartments. Cells from individual FL of
      W42/+ matings also showed an initial ability (at 7 to 8 weeks posttransplant) to
      competitively repopulate both lymphoid and myeloid compartments of myeloablated
      +/+ adult recipients. However, in contrast to recipients of normal or W41/W41 FL
      cells, the repopulation obtained with the W42 mutant stem cells was transient.
      Secondary transplants confirmed the inability of the W42 mutant cells to
      regenerate or even maintain a population of transplantable stem cells. Taken
      together with previous results from studies of CRUs in adult W mice, these
      findings support the concept of changes in the way hematopoietic stem cells at
      different stages of development respond to the stimulatory conditions evoked in
      the myeloablated recipient. In addition, they provide the first definitive
      evidence that SF is a limiting physiological regulator of sustained hematopoietic
      stem cell self-renewal in vivo.

PMID- 9028945
TI  - Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome
      plasmas induce apoptosis in restricted lineages of human microvascular
      endothelial cells.
AB  - Thrombotic thrombocytopenic purpura (TTP) and sporadic hemolytic-uremic syndrome
      (HUS) are thrombotic microangiopathies that occur in the absence of an
      inflammatory response. Ultrastructural features of tissues involved in
      TTP/sporadic HUS suggest an apoptotic process. Consistent with these findings, we
      observed that TTP plasmas induce apoptosis in primary human endothelial cells
      (EC) of dermal microvascular but not umbilical vein origin (Laurence et al, Blood
      87:3245, 1996). We now document the ability of plasmas from both TTP and sporadic
      HUS patients, but not from a patient with childhood/diarrhea-associated HUS, to
      induce apoptosis and expression of the apoptosis-associated molecule Fas (CD95)
      in restricted lineages of microvascular EC. EC of small vessel dermal, renal, and
      cerebral origin were susceptible to induction of Fas and an apoptotic cell death.
      In contrast, microvascular EC of pulmonary and hepatic origin, as well as EC of a
      large vessel, coronary artery, were resistant to both processes. This dichotomy
      parallels the in vivo pathology of TTP/sporadic HUS, with notable sparing of the
      pulmonary and hepatic microvasculature. Apoptotic EC also had some features of a
      procoagulant phenotype, including depressed production of prostaglandin I2
      (prostacyclin). These phenomena support the pathophysiologic significance of
      microvascular EC apoptosis in TTP, extend it to a related disorder (sporadic
      HUS), and suggest consideration of apoptosis inhibitors in the experimental
      therapeutics of these syndromes.

PMID- 9028946
TI  - A collagen-like peptide stimulates tyrosine phosphorylation of syk and
      phospholipase C gamma2 in platelets independent of the integrin alpha2beta1.
AB  - Activation of platelets by collagen is mediated through a tyrosine kinase
      dependent pathway that is associated with phosphorylation of the Fc receptor
      gamma chain, the tyrosine kinase syk, and phospholipase C gamma2 (PLC gamma2). We
      recently described a collagen-related triple-helical peptide (CRP) with the
      sequence GCP*(GPP*)GCP*G (single letter amino acid code: P* = hydroxyproline;
      Morton et al, Biochem J306:337, 1995). The cross-linked peptide is a potent
      stimulus of platelet activation but, unlike collagen, does not support
      alpha2beta1-mediated, Mg2+-dependent adhesion, suggesting that its action is
      independent of the integrin alpha2beta1. This finding suggests the existence of a
      platelet receptor other than alpha2beta1 that underlies activation. In the
      present study, we show that CRP stimulates tyrosine phosphorylation of the same
      pattern of proteins in platelets as collagen, including syk and PLC gamma2.
      Protein tyrosine phosphorylation induced by CRP is not altered in the absence of
      Mg2+ or the presence of monoclonal antibodies (MoAbs) to the integrin alpha2beta1
      (MoAb 6F1 and MoAb 13), conditions that prevent the interaction of collagen with
      the integrin. In contrast, phosphorylation of syk and PLC gamma2 by collagen is
      partially reduced by MoAb 6F1 and MoAb 13 or by removal of Mg2+. This may reflect
      a direct role of alpha2beta1 in collagen-induced signaling events or an indirect
      role in which the integrin facilitates the binding of collagen to its signaling
      receptor. The results show an alpha2beta1-independent pathway of platelet
      activation by CRP that involves phosphorylation of syk and PLC gamma2. This
      pathway appears to contribute to platelet activation by collagen.

PMID- 9028947
TI  - Studies of a second family with the Quebec platelet disorder: evidence that the
      degradation of the alpha-granule membrane and its soluble contents are not
      secondary to a defect in targeting proteins to alpha-granules.
AB  - We recently described a Quebec family with an autosomal dominant bleeding
      disorder characterized by mildly reduced-low normal platelet counts, an
      epinephrine aggregation defect, multimerin deficiency, and proteolytic
      degradation of several, soluble alpha-granular proteins. Similar clinical
      features led us to investigate a second family with an unexplained, autosomal
      dominant bleeding disorder. The affected individuals had reduced to normal
      platelet counts, absent platelet aggregation with epinephrine, and multimerin
      deficiency. Their platelet alpha-granular proteins factor V, thrombospondin, von
      Willebrand factor, fibrinogen, fibronectin, osteonectin, and P-selectin were
      proteolyzed and comigrated with the degradation products found in patients from
      the other family. However, their platelet albumin, IgG, external membrane
      glycoproteins, CD63 (a lysosomal and dense granular protein), calpain, and plasma
      von Willebrand factor were normal, indicating restriction in the proteins
      proteolyzed. Electron microscopy studies indicated preserved alpha-granular
      ultrastructure, despite degradation of soluble and membrane alpha-granular
      proteins. Immunoelectron microscopy studies of the patients' platelets indicated
      that fibrinogen, von Willebrand factor, P-selectin, multimerin, and factor V were
      within alpha-granules, with normal to reduced labeling for these proteins.
      Pathologic proteolysis of alpha-granular contents, rather than a defect in
      targeting proteins to alpha-granules, may be the cause of the protein degradation
      in the Quebec platelet disorder.

PMID- 9028948
TI  - Therapeutic levels of functional human factor X in rats after retroviral-mediated
      hepatic gene therapy.
AB  - Factor X deficiency results in a rare but serious bleeding disorder that might be
      treated by expressing a normal factor X gene in patients. We generated an
      amphotropic retroviral vector with the human FX cDNA and delivered it to rat
      hepatocytes in vivo during liver regeneration. The human alpha1-antitrypsin
      promoter was chosen to direct expression because it was the most efficient of
      several tested in yielding expression of alpha1-antitrypsin protein from a
      retroviral vector in hepatocytes in vivo. We achieved expression of factor X in
      four rats at levels sufficient to maintain hemostasis in humans (10% to 43% of
      normal). The factor X was determined to be functional by using a chromogenic
      substrate assay after immunoprecipitation with human specific antibodies.
      Expression of factor X remained stable for more than 10 months in two rats. It is
      likely that expression will be maintained for the life of the animals, because
      retroviral vectors integrate into the chromosome and hepatocytes are long-lived.
      The high and stable levels of expression achieved using this liver-specific
      promoter overcomes one of the two major obstacles to successful human gene
      therapy for hemophilia.

PMID- 9028950
TI  - Specific accumulation of circulating monocytes and polymorphonuclear leukocytes
      on platelet thrombi in a vascular injury model.
AB  - The adhesion of leukocytes to platelets deposited at the site of vascular injury
      may represent an important mechanism by which leukocytes contribute to hemostasis
      and thrombosis. In this study, we examined whether, in comparison with their
      distribution in circulating blood, certain leukocyte types are enriched at sites
      of platelet deposition. We used an experimental vascular injury model, in which
      human fibrillar collagen was exposed to anticoagulated human whole blood flowing
      through parallel-plate chambers (venous shear rate, 65/s). The platelet-adherent
      leukocytes were detached by EDTA treatment and analyzed by flow cytometry using
      cell-type-specific antibodies. The predominant leukocytes found in platelet
      thrombi were polymorphonuclear leukocytes, accounting for 76% of bound leukocytes
      (62% in circulating blood), whereas T and B lymphocytes did not significantly
      accumulate on thrombi, comprising a fraction of less than 5% (32% in circulating
      blood). Monocytes constituted 16% of platelet thrombus-bound leukocytes, which
      represents an almost fourfold enrichment as compared with their proportion in
      circulating blood. Almost identical results were obtained when we analyzed
      leukocytes adhering to platelet monolayers, which were formed by blocking
      glycoprotein IIb-IIIa, thus preventing platelet aggregation on top of the
      collagen-adherent platelets. Furthermore, leukocyte adhesion to platelet
      monolayers was completely inhibited by an anti-P-selectin antibody (50%
      inhibitory concentration, 0.3 microg/mL), whereas it reached a plateau at about
      70% inhibition on platelet thrombi. This difference could be explained by a
      possible function of glycoprotein IIb-IIIa in leukocyte immobilization to thrombi
      or by the high local concentration of P-selectin in the growing thrombi. The
      results suggest that, because of their known abilities to promote coagulation and
      thrombolysis, the monocytes and polymorphonuclear leukocytes accumulating on
      forming platelet thrombi could play an important role in modulating thrombotic
      and hemostatic processes.

PMID- 9028949
TI  - Characterization of the human platelet/endothelial cell adhesion molecule-1
      promoter: identification of a GATA-2 binding element required for optimal
      transcriptional activity.
AB  - Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kD member of the
      Ig gene superfamily that is expressed on platelets, endothelial cells, and
      certain leukocyte subsets. To examine the factors controlling vascular-specific
      expression of PECAM-1, we cloned the 5'-flanking region of the PECAM-1 gene and
      analyzed its transcriptional activity. 5'-Rapid amplification of cDNA ends (5'
      RACE) analysis showed that transcription initiation occurred at several closely
      spaced nearby sites originating approximately 204 bp upstream from the
      translation start site. Analysis of the sequence immediately upstream from the
      transcription initiation site (TIS) showed no canonical TATA or CAAT elements,
      however an initiator element commonly found in TATA-less promoters encompassed
      the TIS. 5'-serially truncated PECAM-1 promoter segments cloned in front of a
      luciferase reporter drove transcription in both a lineage- and orientation
      specific manner. Putative cis-acting control elements present within a 300-bp
      core promoter included two ets sites, an Sp1 site, tandem E-box domains, two GATA
      associated sites (CACCC), an AP-2 binding site, and a GATA element at -24.
      Mutational analysis showed that optimal transcriptional activity required the
      GATA sequence at position -24, and gel-shift assays further showed that the GATA
      2 transcription factor, but not GATA-1, bound to this region of the PECAM-1
      promoter. Understanding the cis- and transacting factors that regulate the tissue
      specific expression of PECAM-1 should increase our understanding of the
      mechanisms by which vascular-specific gene expression is achieved.

PMID- 9028951
TI  - Molecular mechanism of a mild phenotype in coagulation factor XIII (FXIII)
      deficiency: a splicing mutation permitting partial correct splicing of FXIII A
      subunit mRNA.
AB  - Congenital factor XIII (FXIII) deficiency is potentially a severe bleeding
      disorder, but in some cases, the symptoms may be fairly mild. In this study, we
      have characterized the molecular mechanism of a mild phenotype of FXIII A-subunit
      deficiency in a Finnish family with two affected sisters, one of whom has even
      had two successful pregnancies without regular substitution therapy. In the
      screening tests for FXIII deficiency, no A-subunit could be detected, but by
      using more sensitive assays, a minute amount of functional A-subunit was seen. 3H
      putrescine incorporation assay showed distinct FXIII activity at the level of
      0.35% of controls, and also the fibrin cross-linking pattern in the patients
      clotted plasma showed partial gamma-gamma dimerization. In Western blot analysis,
      a faint band of full-length FXIII A-subunit was detected in the patients'
      platelets. The patients have previously been identified as heterozygotes for the
      Arg661 --> Stop mutation. Here we report a T --> C transition at position +6 of
      intron C in their other allele. The transition affected splicing of FXIII mRNA
      resulting in low steady state levels of several variant mRNA transcripts. One
      transcript contained sequences of intron C, whereas two transcripts resulted from
      skipping of one or two exons. Additionally, correctly spliced mRNA lacking the
      Arg661 --> Stop mutation of the maternal allele could be detected. These results
      demonstrate that a mutation in splice donor site of intron C can result in
      several variant mRNA transcripts and even permit partial correct splicing of
      FXIII mRNA. Further, even the minute amount of correctly processed mRNA is
      sufficient for producing protein capable of gamma-gamma dimerization of fibrin.
      This is a rare example of an inherited functional human disorder in which a
      mutation affecting splicing still permits some correct splicing to occur and this
      has a beneficial effect to the phenotype of the patients.

PMID- 9028952
TI  - Evidence for a large compartment of IgM-expressing memory B cells in humans.
AB  - The recent finding of somatically mutated mu heavy chain transcripts in human
      peripheral blood (PB) B lymphocytes suggests that T-dependent B-cell memory might
      not be restricted to class-switched cells. We provide here evidence that IgM-only
      PB B cells are likely to be the IgM-expressing counterpart of classical (IgM- IgD
      ) memory B cells in humans. As shown by molecular single cell analysis, most IgM
      only cells carry mutated V region genes, like class-switched cells. Although both
      subsets represent populations of nonactivated, resting cells, they express higher
      levels of Ig mRNA than naive (IgM+ IgD+) B cells. IgM-only and class-switched
      cells are CD38- CD77-, and mostly CD23-, thus neither resembling germinal center
      nor naive B cells. Because many IgM-expressing B cells located in secondary
      lymphoid tissues resemble IgM-only PB B cells in terms of cell phenotype, we
      propose that the human lymphoid system contains a large compartment of IgM
      expressing memory cells. Moreover, these cells seem to represent the nonmalignant
      counterparts of IgM-expressing tumor cells in sporadic Burkitt's lymphoma, MALT
      lymphoma, monocytoid B-cell lymphoma, and diffuse large-cell lymphoma that were
      found to harbor somatically mutated V genes.

PMID- 9028953
TI  - Telomerase activity is induced in human peripheral B lymphocytes by the
      stimulation to antigen receptor.
AB  - To understand the molecular events for the proliferation of B cells, we studied
      the induction of telomerase activity in vitro after stimulation to B-cell antigen
      receptor (BCR) on human peripheral B cells. Although unstimulated purified B
      cells of tonsils and peripheral blood from healthy volunteers do not express
      detectable telomerase activity, anti-IgM beads induce telomerase activity in
      these B cells. Soluble anti-IgM antibody (Ab) alone does not induce telomerase
      activity, but the second signal, given by either one of the cytokines of
      interleukin-2 (IL-2), IL-4, and IL-13 or by anti-CD40 monoclonal Ab (MoAb), is
      effective as the costimulation for the induction of the activity. Stimulation
      with anti-IgM Ab and anti-CD40 MoAb induces telomerase activity in most mature B
      cells of the tonsils and peripheral blood. The stimuli to both IgM and IgD
      receptors similarly induce the activity. Induction of telomerase activity is
      accompanied with the proliferation of B cells, but is not absolutely correlated
      with the extent of B-cell growth. Phorbol dibutylate (PDB) plus calcium (Ca)
      ionophore (PDB/Ca), which replace the activation through BCR and the
      costimulatory molecules, also induce telomerase activity. Moreover, it is
      suggested that phosphoinositide (PI) 3-kinase plays a role for the induction of
      telomerase activity in B cells stimulated with anti-IgM Ab and anti-CD40 MoAb.
      These results suggest that telomerase activity is induced in the B-cell
      activation of the antigen specific immune response.

PMID- 9028954
TI  - CD2 regulates the positive selection and function of antigen-specific CD4- CD8+ T
      cells.
AB  - The CD2 glycoprotein has been implicated in both positive and negative regulation
      of T-cell mitogenesis. To study the involvement of CD2 in T-lymphocyte
      development and immune responses, we have analyzed two lines of CD2-null mice,
      each expressing a distinct class I major histocompatibility complex (MHC)
      restricted T-cell receptor (TCR). In both situations, the absence of CD2 appeared
      to promote the positive selection of cells in a manner that is similar to that
      which occurs in the absence of CD5. Consistent with this, compound homozygotes
      that lacked both CD2 and CD5 showed evidence of enhanced positive selection even
      in the absence of a transgenic TCR. Despite the observed enhancement of positive
      selection, the lack of CD2 was associated with defects in proliferative responses
      and interferon-gamma production when transgenic thymocytes and mature T
      lymphocytes were stimulated with the appropriate antigens. These findings raise
      the possibility that impaired sensitivity to selecting ligands in the thymus may
      provide a selective advantage that improves the efficiency of positive selection
      for certain TCRs. Furthermore, the results highlight the potential for a
      differential role for CD2 in thymocyte selection and T-cell immune responses.

PMID- 9028955
TI  - Analysis of the human interleukin-6/human interleukin-6 receptor binding
      interface at the amino acid level: proposed mechanism of interaction.
AB  - The interaction between interleukin-6 (IL-6) and IL-6 receptor (IL-6R) is the
      initial and most specific step in the IL-6 signaling pathway. Understanding its
      mechanism at the amino acid level is the basis for developing small IL-6
      inhibiting molecules. We studied the human IL-6 (hIL-6)/hIL-6R binding interface
      by a combination of molecular modelling and site-directed mutagenesis. Our model
      suggests that the center of the interface between the two molecules consists of
      hydrophobic contacts predicted to account for most of the binding-free energy.
      These contacts can be regarded as a hydrophobic core shielded by hydrophilic
      residues that are also needed for recognition. Following this hypothesis, we
      altered in hIL-6 and hIL-6R residues predicted to reside in the contact region
      and to interact with each other. We studied the capacity of these mutants to form
      an IL-6/IL-6R complex and their ability to transduce the signal. This combined
      approach has led to the identification of certain residue-clusters in the binding
      interface and to a rational explanation of their specific interactions,
      suggesting therein a likely mechanism of complex formation. The results confirm
      the predictive model and strongly support our hypothesis. Comparison with other
      cytokines and their alpha-subunit receptors suggests that the structural location
      of certain binding sites are conserved.

PMID- 9028956
TI  - Thymidine kinase (TK) gene-transduced human lymphocytes can be highly purified,
      remain fully functional, and are killed efficiently with ganciclovir.
AB  - A graft-versus-leukemia (GVL) effect has been considered a major factor
      responsible for cures in patients with hematologic malignancies undergoing
      allogeneic bone marrow transplantation; however, associated graft-versus-host
      disease (GVHD) results in significant morbidity and mortality. T-cell depletion
      reduces the incidence and severity of GVHD but eliminates, at least partially,
      the GVL effect. Reinfusion of donor T lymphocytes at relapse posttransplantation
      can induce a potent antitumor response, but GVHD still occurs in the majority of
      patients. Prior transduction of T lymphocytes with the suicide gene, the viral
      thymidine kinase (TK), permits specific cell kill on administration of
      ganciclovir (GCV). Therefore, infusion of TK-transduced T lymphocytes may induce
      GVL effect and allow for their subsequent selective elimination in case GVHD
      develops. To evaluate the efficacy and feasibility of this promising approach,
      anti-CD3-stimulated primary human lymphocytes cultured in interleukin-2 were TK
      transduced by a retroviral vector carrying both TK and neomycin-resistance genes.
      After selection in G418, more than 90% of the cells contained the TK gene as
      shown by a semiquantitative polymerase chain reaction. In addition, 1 to 5 days
      of GCV exposure, at clinically achievable concentrations of 20 to 50 micromol/L,
      induced > or = 90% killing of G418-selected cells without affecting nontransduced
      cells. Correlation of the extent of T-cell kill and the proportion of TK-gene
      transduced cells is consistent with the absence of a bystander effect. Transduced
      cells were CD3+ and either CD8+ or CD4+ and retained functional properties of
      untransduced cells. In vivo administration of GCV prevented tumor development
      after subcutaneous injection of TK-transduced murine myeloma cells (MOPC-11),
      whereas such an effect was not observed on injection of untransduced cells into
      the opposite flank. Our studies provide critical information that (1) adequate
      numbers of TK-transduced lymphocytes can be selected efficiently with > or = 90%
      purity, (2) selected cells remain functional, (3) 24 hours of exposure to GCV at
      clinically achievable concentration effects > or = 90% killing of selected cells,
      and (4) GCV is effective in vivo in killing TK-transduced cells. Based on these
      data, a clinical study has been initiated in patients with multiple myeloma with
      persistent or relapsing disease after T-cell-depleted allogeneic transplants.

PMID- 9028957
TI  - Clincal, immunologic, and genetic features of an autoimmune lymphoproliferative
      syndrome associated with abnormal lymphocyte apoptosis.
AB  - Programmed cell death (apoptosis) of activated lymphocytes is critical to immune
      homeostasis. The cell surface protein Fas (CD95) and its ligand play a pivotal
      role in regulating lymphocyte apoptosis, and defective expression of either Fas
      or Fas ligand results in marked over accumulation of mature lymphocytes and
      autoimmune disease in mice. The results of recent studies suggest that defective
      lymphocyte apoptosis caused by mutations of the Fas gene can result in a severe
      autoimmune lymphoproliferative syndrome (ALPS) in humans. To define the clinical,
      genetic, and immunologic spectrum of ALPS, 9 patients and their families were
      extensively evaluated with routine clinical studies, lymphocyte phenotyping,
      genotyping, and in vitro assays for lymphocyte apoptosis. Individual patients
      were followed up for 3 months to 6 years. ALPS was identified in 9 unrelated
      children as manifested by moderate to massive splenomegaly and lymphadenopathy,
      hypergammaglobulinemia, autoimmunity, B-cell lymphocytosis, and the expansion of
      an unusual population of CD4- CD8- T cells that express the alpha/beta T-cell
      receptor (TCR). All patients showed defective lymphocyte apoptosis in vitro.
      Heterozygous mutations of the Fas gene were detected in 8 patients. One ALPS
      patient lacked a Fas gene mutation. Healthy relatives with Fas mutations were
      identified in 7 of 8 ALPS kindreds. These relatives also showed in vitro
      abnormalities of Fas-mediated lymphocyte apoptosis, but clinical features of ALPS
      were not present in the vast majority of these individuals. ALPS is a unique
      clinical syndrome in which in vitro abnormalities of lymphocyte apoptosis are
      associated with abnormal lymphoproliferation and autoimmunity. These findings
      provide evidence that apoptosis of activated lymphocytes is an important
      mechanism for maintaining immunologic homeostasis and self-tolerance in humans.
      Fas gene mutations account for impaired lymphocyte apoptosis in only a subset of
      patients with ALPS.

PMID- 9028958
TI  - Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces
      inhibition of intrathymic T-cell development in hGM-CSF receptor transgenic mice.
AB  - Thymocytes show differential cytokine responses, depending on the stage of
      differentiation. Whether these responses are due to preferential cytokine
      receptor expression or due to downstream signaling mechanisms is unknown. In this
      study, we examined the relationship between receptor expression and T-cell
      proliferation or differentiation using thymocytes from transgenic mice
      constitutively expressing the human granulocyte-macrophage colony-stimulating
      factor (hGM-CSF) receptor. Transgenic CD4- CD8-, CD4+ CD8-, and CD4- CD8+ cells
      proliferated when cultured with hGM-CSF in vitro, whereas CD4+ CD8+ cells failed
      to proliferate. To examine the effect of hGM-CSF receptor signaling on T-cell
      development, we used fetal thymic organ cultures. The addition of exogenous hGM
      CSF resulted in the failure of CD4- CD8- cells to differentiate into CD4+ CD8+
      cells. To more closely identify this maturational inhibition, we reconstituted
      normal fetal lobes with sorted pro-T-, pre-T-, or post-pre-T-precursor cells from
      transgenic mice. The addition of hGM-CSF to these cultures led to a block in both
      pro-T- and pre-T-cell differentiation, whereas the more mature post-pre-T cells
      differentiated normally. We propose that hGM-CSF receptor signaling during T-cell
      development results in a stage-specific inhibition of thymic precursor
      maturation.

PMID- 9028959
TI  - Role of Fas ligand and receptor in the mechanism of T-cell depletion in acquired
      immunodeficiency syndrome: effect on CD4+ lymphocyte depletion and human
      immunodeficiency virus replication.
AB  - Direct killing of CD4+ lymphocytes by human immunodeficiency virus-1 (HIV-1)
      probably cannot account for the magnitude of the loss of these cells during the
      course of HIV-1 infection. Experimental evidence supports a pathophysiologic role
      of the apoptotic process in depletion of CD4 cells in acquired immunodeficiency
      syndrome (AIDS). The Fas-receptor/Fas-ligand (Fas-R/Fas-L) system mediates
      signals for apoptosis of susceptible lymphocytes and lympoblastoid cell lines. A
      number of investigators have recently reported increased expression of the Fas
      receptor in individuals with HIV infection, along with increased sensitivity of
      their lymphocytes to anti-Fas antibody mimicking Fas ligand. We attempted to
      determine the role of Fas-mediated apoptosis in disease progression and viral
      replication. Increased Fas-receptor (CD95) expression on CD4+ and CD8+
      lymphocytes was found in a large group of HIV-1-infected patients compared with
      normal controls; individuals with a diagnosis of AIDS and a history of
      opportunistic infection had significantly more Fas receptor expression than did
      asymptomatic HIV-infected persons and normal blood donor controls (P < .01).
      Triggering of the Fas-R by agonistic anti-Fas monoclonal antibody, CH11, was
      preferentially associated with apoptosis in the CD4+ cells; this effect was more
      pronounced in lymphocytes derived from HIV+ individuals. Soluble and membrane
      bound forms of Fas-L were produced in greater amounts in peripheral blood
      mononuclear cells (PBMC) cultures and in plasma obtained from HIV-1-infected
      persons than from normal controls. Furthermore, triggering of lymphocytes from
      HIV-infected persons by CH11 increased levels of interleukin-1beta converting
      enzyme (ICE), a protein associated with apoptosis. When PBMC were cultured in the
      presence of CH11, p24 production per number of viable cells was decreased as
      compared with the same PBMC without CH11 (P < .01). These findings suggest that
      multiple mechanisms, including increased production of Fas-L by infected PBMC,
      increased Fas-R expression, and induction of a protease of ICE family, may play
      roles in the apoptotic depletion of CD4+ cells in HIV infection.

PMID- 9028960
TI  - Phenotypic and functional evidence for the expression of CD4 by hematopoietic
      stem cells isolated from human fetal liver.
AB  - Expression of the CD4 antigen was observed on human fetal liver, fetal bone
      marrow (BM), and umbilical cord blood progenitors expressing high levels of CD34.
      Using clonal and liquid-culture assays, CD4+ CD34++ Lin- (lineage = CD3, CD8,
      CD10, CD14, CD15, CD16, CD19, CD20, and glycophorin A) fetal liver progenitors
      were found to have a greater proliferative potential than CD4- CD34++ Lin-
      progenitors, whereas the CD4- fraction was more enriched for erythroid
      progenitors. Both the CD4+ and the CD4- progenitor subpopulations also gave rise
      to multilineage engraftment upon transplantation into human fetal bone fragments,
      supportive of B-lymphoid and myeloid growth, or into human fetal thymic
      fragments, supportive of T-cell growth, implanted in scid/scid (SCID) mice.
      However, in SCID-hu mice transplanted with graded doses of donor cells ranging
      from 2.0 x 10(2) to 2.0 x 10(4) cells, BM reconstitution by the CD4+ fraction of
      CD34++ Lin- cells was more frequent than by the CD4- fraction when low numbers of
      cells were injected. These functional data strongly suggest that stem cells
      reside among CD4+ CD34++ Lin- fetal liver cells. This hypothesis was further
      supported by the observations that CD4+ CD34++ Lin- fetal liver cells were
      enriched for CDw90+ (Thy-1), CD117+ (kit), CD123+, HLA-DR+, CD7-, CD38-, CD45RA-,
      CD71-, CD115- (fms), and rhodamine 123(dull) cells, a phenotypic profile believed
      to represent fetal stem cells. Furthermore, all CD4+ CD34++ Lin- fetal liver
      cells also expressed CD13 and CD33.

PMID- 9028961
TI  - Activated cytotoxic T cells as prognostic marker in Hodgkin's disease.
AB  - Although the results of treatment of Hodgkin's disease (HD) have improved
      considerably in the last decades, the disease remains fatal in a minority of
      patients. We have recently shown that numbers of activated cytotoxic T cells
      (CTLs), present in tumor biopsy specimens, differ considerably among individual
      HD patients. Because CTLs are the major effector cells in elimination of
      neoplastic cells, we investigated whether the number of activated CTLs is related
      to the clinical outcome of the individual patient with HD. Activated CTLs present
      in tumor biopsy specimens of patients with nodular sclerosis or mixed cellularity
      HD were identified by immunohistochemistry using an antibody directed against
      granzyme B (GrB), a major constituent of the cytotoxic granules of activated CTLs
      and natural killer cells, and an antibody directed against CD8. The presence of a
      high percentage of GrB+ lymphocytes was found to be an unfavorable prognostic
      marker. The large majority of GrB+ cells were also CD8+, indicating that these
      cells are activated CTLs. Prognosis was found to decrease with increasing
      percentages of GrB+ lymphocytes. Optimal discrimination between patients with
      good and poor prognosis was obtained when the threshold was set at 15% GrB+
      cells; 6 of 10 patients with > or = 15% GrB+ lymphocytes died as a result of the
      disease, as compared with 6 of 70 patients with less than 15% GrB+ lymphocytes (P
      < .0001). In stage-2 patients, the percentage of GrB+ lymphocytes retained its
      predictive value in a multivariate analysis including histology, sex, age,
      erythrocyte sedimentation rate, and the presence of B symptoms as covariables. In
      addition, patients with > or = 15% GrB+ lymphocytes had a shortened progression
      free survival time (P = .002). We conclude that a high percentage of activated
      CTLs present in biopsy material of HD patients is a strong indicator for an
      unfavorable clinical outcome.

PMID- 9028962
TI  - Overexpression of PU.1 induces growth and differentiation inhibition and
      apoptotic cell death in murine erythroleukemia cells.
AB  - PU.1 is a member of the ets family of transcription factors and is expressed in
      Friend virus-induced murine erythroleukemia (MEL) cells as a consequence of
      proviral integration into the PU.1/Spi-1 locus. After induction of MEL cell
      differentiation by treatment with dimethylsulfoxide (DMSO), expression of the
      PU.1/Spi-1 gene decreased before induction of beta-globin gene expression.
      Overexpression of PU.1 by using a zinc-inducible expression plasmid in MEL cells
      resulted in unexpected growth inhibition of the transfectants. When PU.1
      overexpressing transfectants were treated with DMSO, growth inhibition became
      much pronounced and apoptosis was induced. Expression of the beta-globin gene was
      not induced under this condition. Neither growth inhibition nor apoptosis was
      induced in MEL cells after expression of mutant PU.1 proteins with a deletion of
      the activation domain or the DNA-binding Ets domain irrespective of the presence
      of DMSO. Interestingly, beta-globin gene expression was not induced in the
      transfectants expressing the former mutant, whereas it was induced in those
      expressing the latter one in the presence of DMSO. These results indicate that
      overexpression of PU.1 in MEL cells results in growth and differentiation
      inhibition and, in conjunction with DMSO treatment, apoptotic cell death. These
      results also suggest that the activation domain and the Ets domain of PU.1
      contribute differently to induction of these effects.

PMID- 9028963
TI  - Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin
      (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody
      ALK1.
AB  - The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma
      (ALCL), results in the production of the nucleolar protein nucleophosmin
      anaplastic lymphoma kinase (NPM-ALK) protein. This report describes an
      immunocytochemical study of the distribution of ALK and NPM-ALK proteins using a
      new monoclonal antibody, ALK1, that recognizes a formalin resistant epitope in
      both the 80-kD NPM-ALK chimeric and the 200-kD normal human ALK proteins.
      Cytoplasmic and nuclear labeling was seen in the t(2;5)+ SU-DHL-1 and Karpas 299
      cell lines. Normal ALK protein expression was restricted to the central nervous
      system (in scattered neurons, glial cells, and endothelial cells). Two hundred
      and thirty-nine cases of lymphoma and 80 nonhematopoietic tumors were
      immunostained. Antibody ALK1 labeled 53.4% (39 of 73 cases) of CD30+ ALCL. A case
      of ALCL with a t(1;2) translocation was ALK1+. Three cases of CD30- ALCL with
      prominent nucleoli showed a unique pattern of coarse granular cytoplasmic
      labeling. All other tumors, including Hodgkin's disease and lymphomatoid
      papulosis, were ALK1-. These results indicate that reliable immunostaining of
      routine biopsy material for NPM-ALK and ALK proteins is feasible. Such analysis
      is of diagnostic importance, especially because t(2;5)+ ALCL cases have a good
      prognosis with appropriate treatment.

PMID- 9028964
TI  - Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia.
AB  - To clarify whether the expression of the WT1 gene in leukemic cells is aberrant
      or merely reflects that in normal counterparts, the expression levels of the WT1
      gene were quantitated for normal hematopoietic progenitor cells. Bone marrow (BM)
      and umbilical cord blood (CB) cells were fluorescence-activated cell sorting
      (FACS)-sorted into CD34+ and CD34- cell populations, and the CD34+ cells into
      nine subsets (CD34+ CD33-, CD34+ CD33+, CD34+ CD38-, CD34+ CD38+, CD34+ HLA-DR-,
      CD34+ HLA-DR+, CD34+ c-kit(high), CD34+ c-kit(low), and CD34+ c-kit-) according
      to the expression levels of CD34, CD33, CD38, HLA-DR, and c-kit. Moreover, acute
      myeloid leukemic cells were also FACS-sorted into four populations (CD34+ CD33-,
      CD34+ CD33+, CD34- CD33+, and CD34- CD33-). FACS-sorted normal hematopoietic
      progenitor and leukemic cells and FACS-unsorted leukemic cells were examined for
      the WT1 expression by quantitative reverse transcriptase-polymerase chain
      reaction. The WT1 expression in the CD34+ and CD34- cell populations and in the
      nine CD34+ subsets of BM and CB was at either very low (1.0 to 2.4 x 10(-2)) or
      undetectable (< 10(-2)) levels (the WT1 expression level of K562 cells was
      defined as 1.0), whereas the average levels of WT1 expression in FACS-sorted and 
      unsorted leukemic cells were 2.4 to 9.3 x 10(-1). Thus, the WT1 expression levels
      in normal hematopoietic progenitor cells were at least 10 times less than those
      in leukemic cells. Therefore, we could not find any normal counterparts of BM or
      CB that expressed the WT1 at levels comparable with those in leukemic cells.
      These results indicate an aberrant overexpression of the WT1 gene in leukemic
      cells and imply the involvement of this gene in human leukemogenesis.

PMID- 9028965
TI  - Plasmablastic lymphomas of the oral cavity: a new entity associated with the
      human immunodeficiency virus infection.
AB  - We report here a series of 16 highly malignant diffuse large B-cell lymphomas of
      the oral cavity with unique immunohistologic features. Fifteen of these developed
      in human immunodeficiency virus-positive patients. All cases displayed
      morphologic features of diffuse large-cell lymphomas but strikingly differed from
      them in that they showed a minimal or absent expression of the leukocyte common
      antigen as well as of the B-cell antigen CD20. Instead, the tumor cells showed a
      constant reaction with the plasma cell characteristic antibody VS38c and a
      frequent reaction with the CD79a antibody. This, in conjunction with a variable
      expression of cytoplasmic Ig and a monoclonal rearrangement of the Ig heavy chain
      gene in all of the three tested cases confirmed the B-cell nature, the clonal
      origin, and the plasmacellular differentiation of these neoplasms. The majority
      of these tumors were negative for the BCL-6 protein, with the remaining cases
      showing only a partial and weak expression of this antigen. An association with
      the Epstein-Barr virus (EBV) was found in 9 of 15 tested cases showing abundant
      EBV-encoded nuclear RNA transcripts in the absence of EBNA-2. Five of the EBV
      positive cases variably expressed LMP-1. We propose to name these tumors
      plasmablastic lymphomas, in accordance with their morphologic and
      immunohistologic features. Knowledge of this lymphoma entity is important to
      avoid confusion with nonlymphoid malignancies due to the lack of commonly used
      lymphoid markers.

PMID- 9028966
TI  - Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the
      major translocation cluster region and tetraploid chromosome clones.
AB  - Sixty-four cases of mantle cell (centrocytic) non-Hodgkin's lymphomas have been
      analyzed for their cytomorphologic features, proliferation indices, bcl-1
      rearrangements, p53 expression patterns, and DNA content by both interphase
      cytogenetic and DNA flow cytometric analyses. According to cytomorphology, three
      subtypes were recognized: a common, a lymphoblastoid, and a pleomorphic variant
      of mantle cell lymphoma (MCL). Blastoid MCL subtypes were characterized by
      distinctly elevated mitotic counts (57 and 51/10 HPF v 21/10 high-power fields in
      common MCL), proliferation indices (58% and 53% v 27% in common types,
      respectively; P < .001), frequent bcl-1 rearrangements at the major translocation
      cluster locus (59% v 40%), and overexpression of p53 (21% v 6%). However, the
      most interesting finding was a striking tendency of blastoid MCL subtypes to
      harbor chromosome numbers in the tetraploid range (36% of lymphoblastoid and 80%
      of pleomorphic types v 8% of common variants, P < .001), a feature clearly
      separating these neoplasms from other types of B-cell non-Hodgkin's lymphoma and
      possibly being related to cyclin D1 overexpression. Our data indicate that,
      although characterized by a uniform immunophenotype and common biologic
      background, MCL shows a broad spectrum of morphologic features ranging from small
      cell to blastoid types and that the morphologic spectrum is mirrored by distinct
      biologic features.

PMID- 9028968
TI  - Characterization of T-cell clones derived from peripheral blood lymphocytes of a
      patient with transfusion-associated graft-versus-host disease: Fas-mediated
      killing by CD4+ and CD8+ cytotoxic T-cell clones and tumor necrosis factor beta
      production by CD4+ T-cell clones.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is one of the most
      serious adverse effects of blood transfusion. It is generally thought to be
      caused by the infused lymphocytes. Donor-derived cytotoxic T lymphocytes (CTLs)
      directed against the recipient's HLAs, which have escaped the recipient's immune
      system and are proliferating, are considered to attack recipient organs and
      tissues. Despite the seriousness of the disease, the precise mechanism of its
      development remains unclear and no definitive treatment has been developed. With
      the aim of developing an effective treatment, we established and characterized T
      cell clones from peripheral blood lymphocytes (PBLs) of a TA-GVHD patient. Three
      types of clones were established. Type I clones were CD8+ and specifically lyse
      cells that express HLA B52. Type II clones were CD4+, specifically lysed cells
      that express HLA DR15, and proliferated in response to stimulation with cells
      that express DR15. Type III clones were also CD4+, showed no cytotoxic activity
      toward any HLA-expressing cells, and proliferated in response to stimulation with
      cells that express DR15. Furthermore, we found that the Fas/Fas-ligand (Fas-L)
      system is involved in the cytotoxicity of the type I and II clones and that the
      type III clones produce and secrete a large amount of tumor necrosis factor beta
      (TNFbeta) after antigen stimulation. Based on our results, these three types of
      clones can be classified into two categories: those that have the ability to
      induce GVHD directly by cytolysis and that show no cytotoxic activity and those
      that have the ability to cause GVHD indirectly through secretion of cytotoxic
      lymphokines.

PMID- 9028967
TI  - Negative regulation of the erythropoietin gene expression by the GATA
      transcription factors.
AB  - We examined regulation of the human erythropoietin (Epo) gene through the GATA
      sequence in the Epo promoter and showed that Hep3B and HepG2 cells express human
      GATA-2 (hGATA-2) mRNA and protein. Nuclear extracts of QT6 cells transfected with
      hGATA-1, 2, or 3 transcription factors showed specific binding to the GATA
      element in the human Epo gene promoter by gel mobility shift assay. Transient
      transfection of Hep3B cells with hGATA-1, 2, or 3 showed that each of these
      transcription factors significantly decreased the level of expression of Epo mRNA
      as assessed by a competitive polymerase chain reaction. Transient transfection of
      Hep3B cells with hGATA-1, 2, and 3 and an Epo-reporter gene (growth hormone [GH])
      construct showed significant inhibition of the Epo promoter. Antisense
      oligonucleotide for hGATA-2 transcription factor significantly increased the Epo
      protein in Hep3B cells under 1% O2 for 24 hours incubation. Furthermore,
      transient transfection of Hep3B cells with hGATA-1, 2, and 3 and an Epo-reporter
      gene (luciferase) construct also showed significant inhibition of the Epo
      promoter. However, transfection of the mutated GATA sequence of the Epo
      luciferase gene with hGATA-1, 2, and 3 interfere with the inhibition of the Epo
      promoter. We conclude that the hGATA-1, 2, and 3 transcription factors
      specifically bind to the GATA element in the human Epo gene promoter and
      negatively regulate Epo gene expression.

PMID- 9028969
TI  - Host F1 mice pretreated with granulocyte colony-stimulating factor accept
      parental bone marrow grafts in hybrid resistance system.
AB  - In the setting of hybrid resistance, parental C57BL/6 bone marrow (BM) grafts are
      vigorously rejected by lethally irradiated (C57BL/6xDBA/2) F1 mice. However, F1
      mice pretreated by continuous administration of granulocyte colony-stimulating
      factor (G-CSF) with a miniosmotic pump before BM grafting developed day-8 splenic
      colonies of donor origin. This inhibitory effect on rejection was reversible
      because F1 mice regained the capacity to reject parental BM when the pump ceased
      functioning. The appearance of only a small number of colonies with the
      administration of G-CSF soon after BM grafting suggested the importance in
      producing this inhibitory effect of pre-exposure of host mice to G-CSF. Because G
      CSF administration with a syngeneic combination did not influence the number of
      colonies, an altered distribution of grafted precursors was unlikely. The absence
      of a reduction in the number of NK1.1-positive cells in G-CSF-treated mice
      suggested functional impairment of natural killer cells, major effectors in
      hybrid resistance, but further study is necessary to elucidate the mechanism
      underlying this phenomenon. However, our results indicate the importance of G-CSF
      as a regulator in a certain type of immune response and raise the possibility of
      clinical application in transplantation medicine.

PMID- 9028970
TI  - Administration of a CD31-derived peptide delays the onset and significantly
      increases survival from lethal graft-versus-host disease.
AB  - The CD31 monoclonal antibody, LYP21, binds to the CD31 domain 6 and inhibits the
      human mixed-lymphocyte reaction (MLR) in a specific and dose-dependent fashion. A
      synthetic CD31 peptide based on human CD31 epitope (amino acids 551 to 574)
      recognized by LYP21 is equally effective in inhibiting the MLR. In this study, we
      used the murine homolog of CD31 peptide 551 to 574 and a control peptide to study
      the role of CD31 molecule on T-cell activation. In vitro, CD31 peptide inhibited
      the MLR across several major and minor histocompatibility differences in a
      specific and dose-dependent fashion, similar to the results observed in the human
      system. Maximal inhibition was achieved at a dose of 200 microg/mL. In the
      cytotoxic T-lymphocyte (CTL) assay, CD31 peptide inhibited CTL responses by 97%.
      To study the in vivo effect of this peptide, graft-versus-host disease (GVHD)
      across minor histocompatibility barriers was induced in the B10.D2 (H-2d) -->
      BALB/c (H-2d) model. BALB/c recipients received CD31 peptide (100 microg/d), or
      phosphate-buffered saline (PBS), or control peptide (100 microg/d)
      intraperitoneally (IP) for the first 5 weeks. CD31 peptide delayed onset of graft
      versus-host disease and significantly increased long-term survival. Twelve of 14
      mice receiving CD31 peptide survived more than 100 days after transplantation, as
      compared with none of 10 mice receiving PBS and none of five mice receiving
      control peptide (P = .0001). Long-term engraftment of allogeneic bone marrow was
      documented in all transplanted mice by polymerase chain reaction (PCR) analysis
      of microsatellite region in the interleukin (IL)-1beta gene. Our data suggest
      that the CD31 molecule has an important functional role in T-cell activation in
      vitro and in vivo.

PMID- 9028971
TI  - Adenoviral vectors and hematopoietic cells.

PMID- 9028972
TI  - 2-Chlorodeoxyadenosine treatment in the Sezary syndrome.

PMID- 9028973
TI  - Acute idiopathic thrombocytopenic purpura--management in childhood.

PMID- 9028974
TI  - Acute idiopathic thrombocytopenic purpura--management in childhood.

PMID- 9028975
TI  - The G1456 to T mutation in the thrombomodulin gene is not frequent in patients
      with venous thrombosis.

PMID- 9028976
TI  - The education and qualification of thoracic surgeons in the USA.

PMID- 9028977
TI  - Efficacy of ketorolac tromethamine and extrapleural intercostal nerve block on
      post-thoracotomy pain. A prospective, randomized study.
AB  - BACKGROUND: Post-thoracotomy pain causes severe impairment of the respiratory
      function. Epidural analgesia is effective in the treatment of post-thoracotomy
      pain but may give rise to significant side-effects. Other low-risk and cost
      effective analgesic treatments are therefore required. METHODS: Thirty male
      patients who had undergone pulmonary lobectomy entered a prospective, randomized
      trial to evaluate the efficacy of ketorolac tromethamine (Group 2) and
      extrapleural intercostal nerve block (Group 3) with intermittent low-dose
      bupivacaine. Objective and subjective assessment was carried out at 8, 16, 24 and
      48 hours postoperatively. RESULTS: There were no significant differences between
      Groups 1 (control group) and 2. Vital capacity was significantly lower in Group 3
      (p<0.05) than in Group 1 after 16 hours. Forced Vital Capacity was significantly
      higher in Group 2 than in Group 3 after 16 and 24 hours (p<0.05). Peak expiratory
      flow was also significantly better in Group 2 than in Group 3 after 16 hours
      (p<0.05). On-demand opioid consumption was significantly lower in Group 2
      (p<0.001) and Group 3 (p<0.05). No side-effects were observed. CONCLUSIONS:
      Ketorolac tromethamine was effective in the treatment of post-thoracotomy pain.
      Extrapleural intercostal nerve block allowed a significant reduction in the
      consumption of opioids. These analgesic techniques could be useful as low-risk,
      cost-effective and reproducible treatments when more effective techniques, such
      as epidural analgesia, are contraindicated.

PMID- 9028978
TI  - Thoracoscopic lung volume reduction surgery for emphysema.
AB  - Resection of large bullae to decompress adjacent lung tissue with the goal of
      improving pulmonary function has been an accepted surgical approach for many
      years. However, the indication for lung volume reduction is not bullous disease
      but diffuse emphysema and the surgical approach is based on an entirely different
      concept. The resection of the most affected parts of the emphysematous parenchyma
      aims at a reduction of the over expansion of the chest with the goal of improving
      respiratory mechanics. This concept was introduced by Brantigan in 1959, but has
      failed to gain widespread acceptance until recently. Based on the extensive
      experience in lung transplantation for patients with end stage emphysema J. D.
      Cooper reevaluated the idea successfully. He reported remarkable improvements in
      FEV1 and a reduction in hyperinflation after performing bilateral lung volume
      reduction through a median sternotomy. During the last 2 years we performed
      bilateral lung volume reduction in more than 30 patients with diffuse emphysema
      using video assisted thoracoscopy (VAT) and studied the results prospectively. In
      the first 20 patients preoperative mean forced expiratory volume in 1 second
      (FEV1) was 765 ml/sec and improved by a mean of 42% (0-100%) three months
      postoperatively. This gain in FEV1 was already observed at the end of
      hospitalisation approximately two weeks after surgery. The 12 minute walking
      distance improved over 40%. In our highly selected study population we had no
      perioperative mortality. Lung volume reduction is a palliative treatment of
      severe pulmonary emphysema. Currently no data is available on the duration of the
      improvement. In this selected group of patients dyspnea is reduced and pulmonary
      mechanics are improved, with a resulting increase in quality of life.

PMID- 9028979
TI  - Comparison of minimally invasive thoracoscopy versus open thoracotomy for staging
      lung cancer.
AB  - Minimally invasive thoracoscopic staging for lung cancer was compared with re
      staging by open thoracotomy in seventeen patients to evaluate whether videoimaged
      thoracoscopic staging was accurate. Seventeen patients underwent thoracoscopic
      staging initially with a closed videoimaged technique. These same patients then
      underwent an open thoracotomy and re-staging with a therapeutic resection for
      lung cancer. All patients underwent pleural evaluation and biopsy if indicated,
      thoracic hilar and mediastinal lymph node sampling, and then resection of the
      parenchymal lesion via a wedge resection, lobectomy or pneumonectomy. There was
      complete TMN stage correlation between the closed videoimaged thoracoscopic and
      open thoracotomy techniques. This preliminary study suggests minimally invasive
      videoimaged thoracoscopic staging is an accurate method to assess the stage of
      lung cancer to guide rational management.

PMID- 9028980
TI  - Thoracoscopic limited resection of bronchogenic carcinoma in patients over the
      age of 80.
AB  - Video-assisted thoracoscopic surgery (VATS) has emerged as a minimally invasive
      therapy of bronchogenic carcinoma, when the diseases occur in patients unable to
      tolerate open thoracotomy who are 80 years old or older. We report on an 80-year
      old man with poor pulmonary function and an 83-year-old man, who were treated
      with a complete VATS resection of bronchogenic carcinoma. Mean chest tube
      duration of the two patients was one day and mean postoperative hospital stay was
      7 days with an uncomplicated postoperative course. Compared with patients with
      open thoracotomy, there were early mobility, less morbidity, and less mortality.
      We believe that when the indication for treatment of bronchogenic carcinoma in
      patients over the age of 80 with concomitant systemic disorders, a thoracoscopic
      limited resection should be considered.

PMID- 9028982
TI  - Thoracoscopic surgery for lung cancer complicated by emphysema in elderly
      patients. Report of three cases.
AB  - We have experienced three elderly cases who underwent thoracoscopic surgery for
      lung cancer complicated by emphysema. Cases 1, 2 and 3, respectively aged 76, 78
      and 80 years, had required the oxygen therapy preoperatively. Allowing for poor
      pulmonary reserve, a thoracoscopic partial pulmonary resection for lung cancer
      combined with Nd-YAG laser pneumoplasty for emphysema was designed. The
      respective values of forced expiratory volume in one second (FEV 1.0) for cases 1
      and 2 increased from 470 and 820 to 860 and 1620 ml. Reductions in residual
      volumes (RV) for cases 1, 2 and 3 were from 2770, 4940 and 5230 to 2370, 4500 and
      3250 ml. The degrees of respiratory failure in the Hugh-Jones classification for
      cases 1, 2 and 3 were up-graded from V, IV and IV, respectively, to III, II and
      II, postoperatively. In conclusion, our thoracoscopic treatment, designed for
      elderly patients with poor pulmonary reserve, allows improvement of emphysema as
      well as resection of lung cancer.

PMID- 9028981
TI  - Localization techniques for the thoracoscopic resection of pulmonary nodules.
AB  - The recent progress made in endoscopic surgery has increased the number of
      thoracoscopic procedures, especially in the field of pulmonary nodules resection.
      The main problem related to these newly developed surgical procedures is the
      difficulty in locating the target nodule. We describe the techniques we currently
      use to facilitate the localization of pulmonary nodules. These techniques include
      preoperative methylene blue injection and insertion of a hookwire into the lung
      nodule, but also intraoperative palpation (digital and instrumental) and
      ultrasonography.

PMID- 9028983
TI  - Thoracoscopic-assisted pulmonary resection in lung cancer.
AB  - BACKGROUND: Thoracoscopic-assisted pulmonary resection for lung cancer is
      controversial. The appropriateness of this approach has to be compared with the
      golden standard of an open resection. METHODS: This study consists of 66 patients
      with a clinical stage 1 disease. A thoracoscopic exploration was executed in 41
      patients. Only in 16 cases was a thoracoscopic resection finally possible. The
      clinical and pathological TNM classification, the histological types and the
      surgical procedure are reported. The reasons for conversion are documented.
      RESULTS: To investigate the appropriateness of the thoracoscopic approach we
      evaluated only the pathologically proven stage 1 disease in both groups.
      Postoperative complications, hospital stay and survival are compared. CONCLUSION:
      Until now we can conclude that there is no adverse effect on survival because of
      the thoracoscopic approach.

PMID- 9028984
TI  - Videothoracoscopic operative staging for lung cancer.
AB  - The authors describe their experience in performing Videothoracoscopy as the
      first step of the operation in patients affected by lung cancer: they refer to
      this procedure as Videothoracoscopic Operative Staging (VOS). In 286 patients,
      already proposed for curative surgical resection on the basis of conventional
      staging, VOS was carried out in order to reach a conclusive judgement of
      resectability. VOS discovered unsuspected causes of inoperability in 17 patients
      (5.7%), while 269 patients underwent surgical operation but in 9 of them this
      consisted in an exploratory thoracotomy (ET). Furthermore, VOS allowed us to
      assess the operability of 11 patients in whom preoperative computed tomography
      (CT) had suggested unresectability but without providing a definitive judgement.
      Based on their experience the Authors conclude that VOS should be performed in
      every patient affected by lung cancer in order to obtain a more detailed staging
      and to reduce to a minimum the number of ETs. By using VOS it was possible to
      decrease the rate of exploratory thoracotomies to less than 4%.

PMID- 9028985
TI  - Continued experience with thoracoscopic major pulmonary resection.
AB  - Between April 1992 and March 1995, 83 patients underwent video-assisted (VATS)
      thoracoscopic major pulmonary resection (lobectomy: 72, bilobectomy: 4, or
      pneumonectomy: 7). Conversion to open thoracotomy was required in a further 21
      cases (rate=20.2%). There was no in unit mortality; 2 patients died within 30
      days (1.9% overall). Analysis (median values) of the VATS lobectomy cases
      demonstrated; operation time - 135 minutes; blood loss - 80 mls; High Dependency
      stay - 38 hours; total postoperative stay - 7 days. Comparison between 70 VATS
      lobectomies and a simultaneous group of 110 open thoracotomy cases confirmed
      reduced postoperative morphine consumption (83 mg open vs 57 mg VATS; p<0.001).
      One pneumonectomy patient exhibited a transient sympathetic dysaesthesia and one
      lobectomy patient developed a mild post thoracotomy pain syndrome. Long-term
      follow-up of VATS lobectomy for patients with primary bronchogenic carcinoma (49)
      revealed 1 bronchogenic cancer related death during an overall mean follow-up of
      16.5 months.

PMID- 9028987
TI  - Indications for laparoscopic surgery in cases of gynecological malignancies
      (endometrial cancer).
AB  - The role of surgery in the treatment of patients with invasive cervical cancer is
      undisputed, but how radical surgery should be is debatable. Every case requires
      detailed knowledge of the development and spread of cervical cancer. Tumor volume
      is the most important diagnostic factor in cervical cancer and also correlates
      with vascular invasion and lymph node involvement. As radical hysterectomy
      requires in cervical cancer besides the laparoscopically easy performable
      lymphadenectomy also the resection of parametria with sceletonisation of ureters
      we started to treat endometrial cancer with a combined laparoscopic and vaginal
      approach. In patients with the suspicion of stage I endometrial cancer prior to
      laparoscopic staging, the prerequisites of histological grading with ploidy and
      measurement of monoclonal antibodies were performed. All patients underwent a
      general check with radiography, computer tomography, liver scan, bone scan and
      lymphography. The performance of lymphadenectomy in cases of stage I endometrial
      cancer remains a controversial subject. We believe that laparoscopic assisted
      surgical staging of stage I endometrial cancer is an attractive alternative to
      the traditional laparotomy-surgical approach. The change from laparotomy to a
      laparoscopic assisted vaginal approach allows for a similar success rate with the
      less invasive approach. No complications occurred in this series and the results
      of our pilot study were satisfactory.

PMID- 9028986
TI  - Possibilities and limits of operative hysteroscopy: an update on transcervical
      resectoscopic uterine surgery.
AB  - In infertility therapy operative hysteroscopy by means of high-frequency surgery
      has replaced laparotomy in many cases. Thus today the therapy of intrauterine
      synechias, septa and myoma is a major sector in hysteroscopic metroplasty.
      Uterine haemorrhage is another area of indications for transcervical high
      frequency surgery. In menstrual disorders caused by polyps, submucous myoma or
      without any anatomic reason transcervical electrosurgery helps to avoid more and
      more hysterectomies. The increasing importance of this method becomes obvious in
      the 1991-AAGL-Survey according to which within three years the number of
      operative hysteroscopies has risen to 17,298, thus doubled within this period of
      time. The present article based on literature and personal experience gives an
      overview of technical equipment available, complications, operative technics and
      risks. Furthermore, the frequency of success and complications of transcervical
      resectoscopic surgery are also discussed.

PMID- 9028988
TI  - Myomectomy by pelvicoscopy.
AB  - The evolution of laparoscopic techniques has made possible the performance of
      myomectomies by pelviscopy. Our technique implies the incision of myometrium with
      diluted POR 8, the excision of myometrium by scissors and the removal of the
      myoma using a SEMM Enucleator, and finally the suture of one or two layers of the
      wound using a cylinder needle. The myoma is extracted from the abdominal cavity
      using sharp cylindrical morcellators. Our technique does not consider the use of
      monopolar or bipolar energy.

PMID- 9028989
TI  - Bile leak after cholecystectomy significance and treatment: results from the
      National Norwegian Cholecystectomy Registry.
AB  - From April 1993 to July 1995, altogether 3860 procedures were enrolled in the
      Norwegian National Cholecystectomy Registry (NNCR), 777 (20.2%) being open
      operations. 3083 (79.8%) were initiated laparoscopically, 313 (10.2%) of these
      converted to open technique. Mortality within 30 days after open cholecystectomy
      was 1.9%, after a converted procedure 1.0% and 0.14% after laparoscopic
      cholecystectomy (p<0.01). According to the intention to treat principle,
      converted procedures should be included in the laparoscopic group. This gives
      seven deaths after 3083 procedures, i.e. 0.23%. Postoperative death still occurs
      approximately 10 times more frequently after open cholecystectomy (p<0.01).
      However, this is partly due to selection of high risk cases to open technique.
      Postoperative bile leak was observed in 25 patients (0.9%) in the laparoscopic,
      13 (4.2%) in the converted and 19 (2.4%) in the open group. Bile leak contributed
      significantly to serious complications. 37 major problems were observed in 25 of
      the patients (44%). Five patients died (8.8%). Among the 57 bile leak patients,
      common bile duct (CBD) injury was found in 13 (22.8%). Additional 19 CBD injuries
      occurred, presenting with other symptoms such as icterus, or being recognised
      during the first operation. The frequency of CBD injury in the laparoscopic group
      was 14 (0.5%), in the converted group 12 (3.8%) and in the open group 6 (0.8%).
      None of the patients with CBD injury underwent intraoperative cholangiography.
      The present results firstly show that open cholecystectomy cannot be considered a
      safe procedure for high risk patients, secondly, that postoperative bile leak
      contributes significantly to postoperative mortality and hence is a serious
      condition generating from CBD injury in about 1/5 of all cases.

PMID- 9028990
TI  - Conservative hepatic resection for hepatocellular carcinoma of cirrhotic
      patients.
AB  - We evaluated in retrospect the applicability of conservative hepatic resection
      for hepatocellular carcinoma (HCC) of cirrhotic patients. Eighty (14.6%) of 548
      patients with HCC underwent liver resection over a period of 10 years in this
      hospital. They were divided into two groups according to surgical procedures. In
      group I, 22 patients underwent major hepatic resection, and in group II, 58
      patients underwent conservative liver resection. The operative mortality for
      patients in group I was 13.6% while it was 3.5% for those in group II. The
      difference was significant (p<0.05). The five-year survival rate was 22% for
      patients in group I, while it was 21% for group II patients. The rate of HCC
      recurrence was 47.4% for group I patients while it was 57.1% for group II
      patients. The difference was not significant. The tumor-free survival rates at 6
      , 12-, 24- and 36-months were 80%, 75%, 55% and 55% respectively for patients in
      group I, while they were 50%, 42.5%, 42.5% and 42.5% for patients in group II. It
      suggested that conservative liver resection was associated with early recurrence
      of HCC. But the difference of mean tumor-free survival time is not significant
      (35.82+/-5.47 vs 38.63+/-8.05 months, p>0.05). Using Cox's regression analysis,
      the presence of Child's B was identified as an independent adverse prognostic
      factor (p=0.000) for long-term survival. The factors associated with poor tumor
      free survival rate were Child's classification (p=0.008), metastasis (p=0.021),
      liver cirrhosis (p=0.039) and tumor size (p=0.054). By evaluating the operative
      mortality, long-term survival rate, prognostic factors for cumulative survival
      time and tumor-free survival time, it suggests that conservative liver resection
      can be selectively used to treat HCC associated with liver cirrhosis.

PMID- 9028991
TI  - Surgical treatment of hepatocellular carcinoma with biliary tumor thrombi.
AB  - Treatment is always abandoned in those HCC with jaundice, because it is usually
      attributed to the underlying liver cirrhosis and extensive tumor. In this series,
      7 cases (0.8%) of HCC with jaundice were caused by bile duct invasion and tumor
      thrombi (BTT). 57% of cases showed Charcot's triad. 57% of BTT were small HCC,
      significantly higher than the 1.7% of total cases (p<0.05). The growth pattern of
      BTT was all spreading type, significantly higher than the 42% of total operation
      cases (p<0.05). The DNA ploidy of BTT was all aneuploid. 57% of BTT had AFP level
      higher than 400 IU/ml, but it was 27% in total cases. The prognosis is poor in
      those treated with palliative tube drainage. Aggressive hepatic resection was
      proved to be safe and achieved the best results in our limited experience.
      Choledochotomy to remove tumor thrombi is contraindicated because it easily
      causes tumor seeding. It is advocated to search BTT for resection from the group
      of HCC with jaundice.

PMID- 9028992
TI  - Laparoscopic adjustable silicone gastric banding in the treatment of super
      obesity in the Jeddah area, Saudi Arabia. A preliminary report.
AB  - Eighteen morbid and super-obese patients were subjected to laparoscopic
      adjustable silicone gastric banding (LASGB) of the new prototype which is
      currently used in Europe. This prospective study was done during a short period
      of time between October 26, 1995 and January 29, 1996 by one team and in the same
      hospital. Eleven patients were males, while seven were females. The mean age was
      32 years (range 19-55 years), while the mean weight was 138 kg (range 98-191 kg),
      and the mean Body Mass Index (BMI) was 49.8 kg/m2 (range 36.3-65 kg/m2). Although
      most of the patients were super obese, no major operative difficulties were
      encountered and the patients made a good postoperative recovery after this
      technique. The weight loss during this short period was encouraging. The
      literatures are reviewed.

PMID- 9028993
TI  - Recto-colic reflex: role in the defecation mechanism.
AB  - As urge is felt and defecation starts, it is postulated that the colon
      continuously feeds the rectum with stools until the colon is empty. The
      relationship of rectal distension at defecation to colonic activity is not yet
      fully explored. The current communication studies this relationship in 11
      patients (mean age 48.4+/-18.8 years, 6 men and 5 women) with transverse
      colostomy performed after transverse colectomy for cancer of the transverse
      colon. The rectum was distended by a condom-ended catheter in increments of 10 ml
      of H20, and the pressures in the right and left colon were measured by balloon
      catheters introduced through the colostomy. The test was repeated after
      anesthetizing the rectum or colon, respectively. Upon rectal distension up to
      sensation of urge, there was no colonic pressure response. At urge (mean
      distension volume of 160+/-36.7 ml), the left colonic pressure showed a
      significant rise (p<0.001), while the right colon revealed no response (p>0.05).
      Rectal distension during rectal or colonic anesthetization effected no colonic
      pressure response (p>0.05). The left colonic contraction upon rectal distension,
      being reproducible and absent with the anesthetized rectum or colon, postulates a
      reflex relationship which we call "recto-colic reflex". This reflex acts at
      defecation to feed the rectum successively with fecal material until the colon is
      emptied. Reflex derangement may play a role in defecation disorders.

PMID- 9028994
TI  - Acute appendicitis in pregnancy. A review of 52 cases.
AB  - Acute appendicitis in pregnancy is the most common non-obstetric complication
      warranting emergency laparotomy. A retrospective study of 52 pregnant patients
      who underwent laparotomy for suspected acute appendicitis between June 1982 and
      June 1995 revealed a histopathological diagnosis in 29 (56%) patients. The
      hospital incidence for acute appendicitis in pregnancy was 0.09% (1 in 1102
      deliveries). There were 10 (19%) patients who presented in the first trimester,
      31 (60%) second trimester, 8 (15%) third trimester and 3 (6%) patients in the
      puerperium. Abdominal pain in the right lower quadrant was the most common
      presenting symptom. Abdominal tenderness and rebound tenderness were the most
      common physical signs, although the latter was less marked in late pregnancy.
      Preoperative laboratory investigations were equivocal in reaching a decision for
      surgical intervention. Laparotomy was performed within 24 hours of onset of
      symptoms in 67% of patients. Perforation of the appendix was found in 4 (14%)
      patients, all of whom had symptoms exceeding 24 hours. Wound infection occurred
      in 4 (9.6%) patients, 3 of whom had a perforated appendix. There were 2 (9%)
      fetal losses among the patients with negative laparotomies. Five (17%) other
      fetuses were lost in the group with diseased appendix, three of these were in
      patients with perforated appendix. There was no maternal death in the study.

PMID- 9028995
TI  - Complications of 867 thyroidectomies performed in a region of endemic goiter in
      Turkey.
AB  - This article aims to define the incidence of complications in 867 thyroidectomies
      performed by residents with attending surgeons' supervision as part of a training
      programme, in a region of endemic goiter. Seven hundred and nine patients were
      female and 158 were male. The age of the patients ranged between 6 and 76 and
      mean age was 32.5. Cases were divided into two groups according to their disease
      nature. Group 1 included 805 patients with nodular colloidal goiter (NCG) and
      adenomas. The remaining 62 cases, 25 with recurrence of goiter (RG), 21 with
      thyroid malignancy (TM) and 16 with thyroiditis formed group 2. While the overall
      complication rate was 11.3% (93 cases) in group 1, it was 20.9% (13 cases) in
      group 2. The mortality rate was zero in both groups. The incidence of
      complications of 867 thyroidectomies performed by residents with the attending
      surgeons' supervision was within acceptable limits especially as far as group 1
      was concerned. However we suggested that attending surgeons themselves,
      disregarding residents training, should perform the operation in special cases
      such as recurrent goiters, thyroid carcinomas with positive regional lymph nodes
      and thyroiditis with regional adhesions.

PMID- 9028996
TI  - The use of thallium-201 and technetium-99m subtraction scintigraphy for the
      localisation of parathyroid adenomas.
AB  - Parathyroid adenomas account for approximately 85% of cases of primary
      hyperparathyroidism. Several preoperative localisation techniques exist to aid
      the surgeon during neck exploration, with varying degrees of success. We report
      on the results of a modification of the established technique of thallium and
      technetium subtraction scintigraphy. The operative findings of 60 patients
      undergoing neck exploration for parathyroid adenoma were correlated with
      preoperative thallium and technetium subtraction scintigraphy scans. The radio
      isotopes were administered in the reverse order to conventional administration,
      resulting in enhanced imaging. The adenomatous glands were correctly localised in
      all cases. The 100% sensitivity of this modified scanning technique supports a
      strategy of unilateral scan-directed neck exploration.

PMID- 9028997
TI  - Splenic preservation after traumatic rupture. A remote hospital experience.
AB  - OBJECTIVE: The aim of this study is to describe the outcome of treatment
      modalities, the length of hospital stay and blood transfusion requirements of
      patients with traumatic splenic rupture. It also discusses the pros and cons of
      each treatment given, to determine its feasibility and pre-requisites in a set-up
      similar to this one. SET-UP: The Royal Commission Medical Centre is a 340-bed
      secondary care facility located in Yanbu Industrial City, in the western part of
      Saudi Arabia. It serves the population of the city (approximately 40,000) plus a
      catchment area of nearly 300,000. METHODS: A retrospective cross-sectional design
      was used in this study. The medical records were reviewed to abstract the
      required data. RESULTS: Twenty-one patients (15 males, 6 females) were included.
      The age ranged between 4 and 57 years, with a mean of 20.8 years and a SD of 13.3
      years. A total of 14 spleens (66.6%) were preserved. Non-operative treatment
      (active conservative) was given to 12 patients while two spleens were preserved
      operatively by splenorraphy. Seven (33.3%) had operative treatment in the form of
      splenectomy. The blood transfusion requirement was significantly less in the non
      operative treatment modality (p<0.005). The outcome of treatment was
      significantly better in the non-operative treatment modality (p<0.005). The
      length of hospital stay was not statistically significantly different.
      CONCLUSION: Active-conservative treatment is a viable and safe alternative in
      stable patients with splenic injury due to blunt trauma when intensive care and
      monitoring facilities are available and properly utilized.

PMID- 9028998
TI  - Clinical and histologic determinations of adequate breast resection in breast
      conserving surgery. A review.
AB  - Patient selection is an important consideration in breast-conserving therapy
      (BCT), and is dependent on the clinical and histologic determination of disease
      extent. In order to provide adequate local control without compromising cosmetic
      outcome, the amount of breast tissue that must be excised in BCT needs to be
      individualized. Nuclear magnetic resonance (NMR) imaging can provide better
      information than mammography or ultrasonography for assessing multifocal and
      multicentric disease in the breast. However, they will play a limited role in
      breast cancer staging until NMR imaging-directed sterotaxic biopsy becomes
      available. On the other hand, the histologic status of the surgical margins as
      well as certain features of the tumor including the presence of intraductal
      components is predictive of the extent of breast cancer. It is reasonable to
      evaluate and obtain clear margins when performing BCT. However, further
      investigation of new preoperative imaging and intraoperative staging modalities
      for assessing multifocal and multicentric disease is necessary.

PMID- 9028999
TI  - Hemostatic efficacy and safety of TachoComb in surgery. Ready to use and rapid
      hemostatic agent.
AB  - TachoComb is a new, ready-to-use hemostatic agent consisting of a collagen sheet
      coated on one side with human fibrinogen, bovine thrombin, and bovine aprotinin.
      The product was used in 125 surgical operations (vascular, hepatic, urological
      and ENT) in which secondary hemostasis was required. It was placed over the cut
      surface or over the edges of the wound. The investigating surgeons expressed
      their opinion on the intra- and postoperative hemostatic efficacy, and routine
      laboratory tests were done postoperatively. TachoComb had good hemostatic
      efficacy in 67.2% of cases, and very good in 22.4%. No noteworthy systemic
      changes were observed. As an adjuvant to obtain complete hemostasis in surgery,
      TachoComb is effective, practical and quick to use, and is very well tolerated.

PMID- 9029000
TI  - Angiomyolipoma of the liver.
AB  - Angiomyolipoma, a form of mixed mesenchymal tumor, a not uncommon tumor of the
      kidney, is rarely found in the liver. We report a case of angiomyolipoma of the
      liver in a 34-year-old woman, in whom diagnosis was made by computed tomography
      (CT), magnetic resonance imaging, superior mesenteric and celiac trunk
      angiography and histological examination. The treatment of choice was a
      successful extended right hepatectomy.

PMID- 9029001
TI  - An air leak free and self retaining cannula for laparoscopic surgery.

PMID- 9029002
TI  - The dendritic cell lineage in haemopoiesis.

PMID- 9029003
TI  - Molecular defects in Hb H hydrops fetalis.
AB  - The molecular defect in two unique cases of Hb H hydrops fetalis has been
      characterized. Both cases are due to co-inheritance of a 'non-deletion' defect
      affecting the alpha2 gene: at codon 30 delta GAG, Glu) and codon 59 (G --> A, Gly
      --> Asp) respectively, and a zeta-alpha thalassaemia (thal) 1 or alpha thal 1
      genotype. These two non-deletion defects, unlike previously described cases,
      resulted in severe anaemia of the fetuses and emphasize the importance of
      performing prenatal diagnosis for these families.

PMID- 9029004
TI  - Molecular analysis of the Turkish form of deletion-inversion (delta beta)(0)
      thalassaemia.
AB  - Two unrelated (delta beta)(0)-thalassaemia patients from Southern Turkey are
      presented. DNA studies indicated that both of them are homozygous for the Turkish
      type of (delta beta)(0)-thalassaemia characterized by one large deletion of 11.5
      kb including the delta and beta globin genes at the 5' end and one small deletion
      of 1.6 kb at the 3' end, which are separated by an inverted 7.6 kb long DNA
      segment that includes L1 repetitive sequence. In the present study a PCR-based
      method was performed to produce a unique deletion-specific product and subjected
      to sequence analysis for the determination of the breakpoint. DNA polymorphisms
      in the beta-globin gene cluster of deletion-inversion type of (delta beta)(0)
      thalassaemia, IVS-I-6 and beta-39 globin genes were examined. Analysis of
      sequence variations in regulatory regions including the 5' hypersensitive site-2
      of the locus control region (LCR), the delta, (G)gamma and (A)gamma 5' flanking
      regions and the second intervening sequence (IVS-II) of (A)gamma and (G)gamma
      genes indicated the presence of close similarities between the chromosome
      carrying the Turkish form of deletion-inversion (delta beta)(0)-thalassaemia and
      the chromosome associated with beta-39 nonsense mutation in haplotype II. These
      two chromosomes are characterized by the presence of a 4 base pair deletion in
      the (A)gamma(T) globin gene promoter. A C --> T alteration at position -199 5' to
      the delta gene was also found to be associated with the Turkish type of (delta
      beta)(0)-thalassaemia and beta-39 chromosome.

PMID- 9029005
TI  - Inadequate erythropoietin response to anaemia in HIV patients: relationship to
      serum levels of tumour necrosis factor-alpha, interleukin-6 and their soluble
      receptors.
AB  - Severe anaemia is a frequent complication in advanced HIV infection. In our study
      we investigated the interaction between cytokine network, HIV infection and
      erythropoietin (Epo) response with increasing anaemia levels. No correlations
      could be established between circulating tumour necrosis factor (TNF)-alpha and
      any of the examined parameters. However, a negative correlation was found between
      haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r = -0.54; P <
      0.001; sTNF-R II: r = -0.47; P < 0.001) as well as interleukin-6 levels (r = 
      0.29; P < 0.01). In contrast, no significant increase in log[Epo],
      counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors,
      was found. In patients classified as stage III, according to the Centers for
      Disease Control (CDC) classification, the erythropoietin response was
      significantly more impaired than in patients from CDC groups I and II (P < 0.01).
      The results of this study suggest that similar to its action in vitro, activation
      of the TNF/TNF-R system may impair erythropoietin production in HIV-associated
      anaemia. Due to the brief half-life of TNF-alpha, this activation is particularly
      reflected by elevations of soluble TNF receptor levels.

PMID- 9029006
TI  - The sensitivity of Fanconi anaemia group C cells to apoptosis induced by
      mitomycin C is due to oxygen radical generation, not DNA crosslinking.
AB  - Fanconi's anaemia (FA) is characterized by increased spontaneous and induced
      chromosome fragility. This has been widely regarded to be due to a defect in DNA
      crosslink repair, because of the sensitivity of cells to known DNA crosslinking
      agents such as mitomycin C (MMC) and diepoxybutane (DEB). Although Fanconi cells
      are also sensitive to molecular oxygen, and may be protected by antioxidants,
      this has generally been considered to be a secondary phenomenon. However, it has
      recently been demonstrated that the FAC protein, coded for by the Fanconi anaemia
      gene for complementation group C, is strictly cytoplasmic and does not enter the
      nucleus even after DNA damage, which seems inconsistent with a role in DNA
      repair. We have studied the effects of MMC and oxygen on apoptotic cell death in
      FA group C (FA-C) and normal lymphoblastoid cell lines. Hyperoxia alone failed to
      induce apoptosis in either FA-C or normal cells. At ambient oxygen, MMC is known
      to generate oxygen free radicals, whereas decreased oxygen tension facilitates
      the metabolic activation of MMC for DNA crosslinking. We therefore studied the
      effects of MMC at 20% and 5% oxygen to favour oxygen radical generation or DNA
      crosslinking respectively. FA-C cells showed increased sensitivity compared to
      normal cells for the induction of apoptosis by MMC at 20% oxygen. When cells were
      treated with MMC at 5% oxygen we found no increased sensitivity of Fanconi cells
      to MMC when compared to normal cells. These results imply a role for oxygen free
      radicals, but not for DNA crosslinking, in the sensitivity of FA cells to MMC.

PMID- 9029007
TI  - Iron metabolism in transgenic mice with hypoplastic anaemia due to incomplete
      deficiency of erythropoietin.
AB  - Iron overload is a serious complication of many forms of anaemia, arising in part
      from mechanisms associated with compensatory increases in erythropoiesis. To
      investigate other mechanisms by which anaemia itself may perturb iron metabolism,
      without the confounding effects of compensatory erythropoiesis, we studied
      transgenic mice with a partially disabling insertion in the erythropoietin gene,
      which manifested as incomplete erythropoietin deficiency. Mice were studied aged
      7-8 weeks. Haemoglobin concentrations were 6.6 +/- 0.8 g/dl in mice homozygous
      for the modified erythropoietin gene, 12.9 +/- 2.2 g/dl in heterozygous mice and
      14.1 +/- 1.0 g/dl in controls. Homozygous mice showed significant hepatic iron
      loading (2-fold increase in liver non-haem iron, compared with heterozygous mice
      and normal controls, with iron staining principally in the periportal
      hepatocytes). Absorption studies using 59Fe showed increased uptake from the
      lumen of an in vivo isolated duodenal segment in homozygous mice, although at
      this point in time overall transfer of radioiron to the circulation and other
      tissues (mucosal transfer) was not different from controls. These observations
      demonstrate that anaemia can lead to hepatic iron loading even in the absence of
      increased erythropoiesis, and are consistent with the possibility that anaemic
      hypoxia can enhance mucosal iron uptake by the duodenal enterocyte.

PMID- 9029009
TI  - The mechanism of red cell (dis)aggregation investigated by means of direct cell
      manipulation using multiple optical trapping.
AB  - We used multiple optical trapping to study the mechanism of red cell
      (dis)aggregation. Two sets of optical 'tweezers' were used to bring two red blood
      cells together to form a two-cell aggregate and then to pull them apart, to study
      the interaction between the cells. We found that cross-bridging occurred in
      normal reversible aggregation as we observed binding and the occurrence of small
      tethers between opposite cell membranes. Furthermore, the cells could only be
      parted by sliding them side by side with a maximum velocity in the order of
      microm/s indicating accumulation of the cross-bridges.

PMID- 9029008
TI  - Agranulocytosis, arthritis and systemic vasculitis in a patient receiving the
      oral iron chelator L1 (deferiprone).
AB  - A thalassaemic girl presented with agranulocytosis, arthritis of both ankles and
      clinical and laboratory features consistent with the diagnosis of systemic
      vasculitis, during oral iron chelator L1 (deferiprone) treatment. Changes in the
      humoral and cell-mediated immune function. including antinuclear antibodies
      (ANA), anti-DNA and extractable-nuclear antigens (ENA) antibodies positivity,
      increased immunoglobulin values, decreased T suppressor and the presence of
      circulating immune complexes, suggest a cause-and-effect relationship with the
      observed clinical manifestations. A careful monitoring of the immune function is
      recommended in patients who are receiving the oral iron chelator L1.

PMID- 9029010
TI  - Administration of G-CSF to healthy subjects: the effects on eosinophil counts and
      mobilization of eosinophil granule proteins.
AB  - Any influence of G-CSF on eosinophils is mostly negative, although reports which
      have studied this relationship are few with varied results. The aim of this study
      was to investigate the influence of G-CSF administration to healthy subjects on
      eosinophils in peripheral blood. Blood eosinophil counts, serum levels of
      eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil
      protein X (EPX), as well as cell morphology were studied. 14 healthy volunteers
      received 7.5 microg (n = 8) or 10 microg/kg body weight (n = 6) G-CSF daily for
      six consecutive days. ECP and EPX were assessed by specific RIAs and EPO by a
      specific FEIA. Cell morphology was examined by electron microscopy. During G-CSF
      administration, eosinophil counts increased from 0.22 +/- 0.04 x 10(9)/l to 0.61
      +/- 0.098 x 10(9)/l (P = 0.001), serum ECP from 12.39 +/- 2.45 microg/l to 61.82
      +/- 7.38 microg/l (P = 0.0014), serum EPX from 28.05 +/- 4.54 microg/l to 87.86
      +/- 9.84 microg/l (P = 0.002) and serum EPO from 8.89 +/- 2.2 microg/l to 19.98
      +/- 5.1 microg/l (P = 0.003). All variables returned gradually to initial values
      after discontinuation of G-CSF. Distinct changes in the morphology of secondary
      granules were observed 24 h after G-CSF administration. The granules became
      irregular and their matrix less electron dense. We conclude that administration
      of G-CSF to healthy humans increases the number of circulating eosinophils and
      affects the mobilization of eosinophil granule proteins.

PMID- 9029011
TI  - Clonal expansion of Vgamma3/Vdelta3-expressing gammadelta T cells in an HIV-1/2
      negative patient with CD4 T-cell deficiency.
AB  - Immunological investigations were carried out in an HIV-1/2//HTLV-1-negative
      patient with CD4 T-cell deficiency (0.357-0.6 x 10(9)/l) and expansion of
      gammadelta T cells which accounted for 26-42% of peripheral blood lymphocytes
      during an observation period of 3 years. Flow cytometry analyses with a panel of
      available Vgamma/Vdelta-specific monoclonal antibodies indicated that the
      pathologically expanded gammadelta population expressed Vgamma2 or Vgamma3 paired
      with Vdelta3 on the surface but lacked the expression of activation antigens such
      as CD38 or CD71. Cloning and sequencing of RT-PCR products obtained after
      amplification of cDNA with Vgamma-Cgamma and Vdelta-Cdelta specific primers
      confirmed the presence of a clonally expanded Vgamma3/Vdelta3 population in the
      peripheral blood of this patient. Cytotoxicity assays performed with purified
      gammadelta T cells as effectors and resting or preactivated autologous CD4 T
      cells as targets failed to reveal evidence for autoreactive cytotoxicity of
      Vgamma3/Vdelta3 cells as a possible mechanism of CD4 T-cell deficiency in this
      patient.

PMID- 9029012
TI  - Persistent polyclonal B-cell lymphocytosis in identical twins.
AB  - This is the first report of the unusual syndrome of persistent polyclonal B-cell
      lymphocytosis occurring in monozygotic twins. The syndrome is characterized by a
      lymphocytosis, with circulating atypical, binucleated lymphocytes, mild
      splenomegaly and raised serum IgM. It occurs predominantly in females, with
      serological evidence of previous EBV infection, and is associated with cigarette
      smoking and HLA-DR7 phenotype. The association with .DR7 suggests a genetic
      predisposition. Its occurrence in identical twins, documented here, provides
      stronger support for a hereditary/genetic basis for the syndrome.

PMID- 9029013
TI  - Analysis of CD9, CD32 and p67 signalling: use of degranulated platelets indicates
      direct involvement of CD9 and p67 in integrin activation.
AB  - The use of agonist monoclonal antibodies (mAbs) to probe the signalling function
      of platelet membrane proteins is severely limited by the dependence of the mAb
      effect on Fc-FcgammaRII interaction. Furthermore, in addition to its anchoring
      role, the FcgammaRII receptor itself generates a stimulation signal resulting in
      granule secretion. Platelet stimulation by the released granule contents can then
      further obscure the original activation signal. Here we demonstrate that these
      problems are largely overcome by the use of platelets which had been degranulated
      with thrombin prior to stimulation with mAbs. We found that, like intact cells,
      degranulated platelets could also be activated and induced to aggregate by mAbs
      against a 67 kD membrane protein (known as PTA1) and CD9, and by crosslinked CD32
      (FcgammaRII). However, the signal generated by crosslinked FcgammaRII was weak
      compared with that induced by the other monoclonal antibodies. Thus, by
      diminishing the FcgammaRII signal contribution, we have succeeded for the first
      time to clearly dissect the target antigen signal from that generated by
      FcgammaRII. In addition to differences in the degree of aggregation, analysis of
      the signals generated by each mAb showed differences in Ca2+ fluxes and protein
      phosphorylation. Moreover, the signals generated by CD9 and PTA1 antigens
      differed significantly in their sensitivity to PKC inhibition or ADP-ribosylation
      of the small GTP-binding protein rhoA. Despite these differences, the signals
      initiated by all three antigens converged to a common signalling pathway which
      included activation of tyrosine kinase(s). The pattern of protein phosphorylation
      strongly resembled that induced by gpIIb/IIIa-mediated platelet interaction with
      macromolecular ligands and by mutual cell contact. The multiple intercellular
      links formed by mAb would have a similar effect since the Fc-receptor anchorage
      required for antigen stimulation is already known to be provided by adjacent
      cells. The present findings suggest that the function of both CD9 and PTA1
      antigens is closely associated with gpIIb/IIIa activation.

PMID- 9029015
TI  - In vivo coagulation activation following infusion of highly purified factor XI
      concentrate.
AB  - The use of factor XI concentrates has been associated with thrombosis. Plasma
      markers of coagulation activation were measured before and 30, 60, 120 and 240
      min after six infusions of the BPL factor XI concentrate. Five studies were
      completed before surgical intervention, one was undertaken in a patient with an
      intracerebral haemorrhage. Significant elevation of levels of fibrinopeptide A
      (FpA) (P < 0.05) and thrombin-antithrombin (TAT) were demonstrated following six
      infusions and prothrombin fragment F1.2 following four. Levels of all three
      markers had risen 60 min following concentrate administration and FpA levels
      remained elevated throughout the study period. Levels of D-dimer rose in four
      patients at 240 min. These results indicate significant thrombin generation by 60
      min and subsequent plasmin generation consistent with coagulation activation by
      the factor XI concentrate. The greatest elevation of activation markers was seen
      in those subjects with pre-existing coagulation activation. We advise caution in
      the use of these products and awareness of the risks in patients who may already
      have activated coagulation states.

PMID- 9029014
TI  - Defective response to thrombopoietin and impaired expression of c-mpl mRNA of
      bone marrow cells in congenital amegakaryocytic thrombocytopenia.
AB  - Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in
      newborns and infants, characterized by isolated thrombocytopenia and
      megakaryocytopenia in the first year without physical anomalies. The defect of
      thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand
      for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in
      vivo studies indicate that TPO plays a key role in the regulation of
      megakaryocytopoiesis. In this study we examined the effect of TPO on
      megakaryocyte colony formation from a patient with CAMT using a plasma-containing
      methylcellulose clonal culture. The in vitro results demonstrated a defective
      response to TPO in megakaryocyte colony formation from bone marrow mononuclear
      cells (MNC) of the patient. although interleukin-3 (IL-3) but not stem cell
      factor (SCF) induced only a small number of megakaryocyte colonies. These
      findings indicated that thrombocytopenia in CAMT could not be corrected by
      administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL
      3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic
      progenitors in the bone marrow of the patient. The serum TPO level measured by
      enzyme-linked immunosorbent assay was significantly higher than that in healthy
      controls. By PCR, marrow MNC from healthy children and from a patient with
      essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected
      in marrow MNC from the patient with CAMT. There was no difference in the CD34
      expression and c-kit mRNA between the CAMT patient and healthy children. The
      results of this study suggest that the pathophysiology in CAMT may be a defective
      response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.

PMID- 9029016
TI  - Two novel alleles of the ATCT variable number tandem repeat locus VWF.VNTR I in
      intron 40 of the von Willebrand factor gene.
AB  - Two new alleles, allele 9 and allele 15, of the ATCT variable number tandem
      repeat locus, VWF.VNTR I, of intron 40 of the von Willebrand factor (VWF) gene
      are described. Both alleles occurred in low frequencies, being detected in only
      two and one of 285 random Australian Caucasians respectively. In all, 10 alleles
      were observed representing between six and 15 repeats of the ATCT motif. The
      allele frequency distribution in this Australian population was similar to other
      VWF.VNTR I population studies. The additional alleles described here for the
      VWF.VNTR I further enhance the usefulness of this VNTR locus in human
      identification work.

PMID- 9029017
TI  - Expression of intercellular adhesion molecule 1 (ICAM-1) in childhood acute
      lymphoblastic leukaemia: correlation with clinical features and outcome.
AB  - To investigate whether expression of intercellular adhesion molecule 1 (ICAM-1,
      CD54) in childhood acute lymphoblastic leukaemia (ALL) has an impact on the
      biological behaviour of the disease, we evaluated 751 children of the ALL-BFM 90
      trial with B-cell precursor- (n = 677) or T-cell-ALL (n = 74) for CD54 expression
      within immunological subgroups, its correlation to certain clinical features, and
      therapy outcome. The highest percentage of patients expressing CD54 was found in
      common- and pre-B-ALL (76.1% and 61.4%, respectively). There was intermediate
      expression in pre-pre-B-ALL (47.8%), and the lowest expression was detected in T
      ALL (12.2%). A significant positive correlation could be demonstrated between low
      CD54 expression (< 20% stained blasts) and high peripheral leucocyte counts,
      central nervous system (CNS) involvement, and splenomegaly at the time of
      diagnosis (P < 0.01). In addition, CD54 expression was a favourable but not
      independent prognostic factor. Event-free survival estimate at 4.5 years was 86%
      for CD54+ patients (n = 463), compared with 78% for CD54- patients (n = 241) (P <
      0.01). These findings demonstrate that CD54 expression has an impact on
      dissemination patterns and outcome of childhood ALL, and emphasizes the potential
      relevance of adhesion mechanisms in influencing clinical characteristics and
      prognosis of haematological malignancies.

PMID- 9029018
TI  - Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene
      status.
AB  - In this study we investigated the presence of structural lesions in the ALL-1,
      p53 and p16 (cyclin-dependent kinase 4 inhibitor) genes in leukaemic cells
      obtained from 22 patients with infant acute leukaemia (aged < 18 months). Of
      these, 18 cases were classified as acute lymphoblastic leukaemia (ALL) and four
      as acute myeloid leukaemia (AML). Tumour DNAs were analysed by a combination of
      Southern blot. polymerase chain reaction (PCR), single-strand conformation
      polymorphism (SSCP), and direct sequence analyses. The results showed ALL-1 gene
      rearrangements in 15/22 (68%) cases, p53 gene mutations in 5/22 (26%), and a
      homozygous deletion of p16 in a single T-ALL case. p53 and p16 alterations were
      all found in the group of patients with ALL-1 gene rearrangements. p53 mutations
      were more often associated with a myeloid phenotype (3/5). In summary, multiple
      molecular alterations were found in 6/15 (40%) infant acute leukaemias with ALL-1
      rearrangements. As to the clinical course, patients with additional lesions had
      similar clinical outcome with respect to patients with ALL-1 gene rearrangement
      as the sole genetic aberration. This may support the hypothesis that ALL-1
      alterations are genetic events per se sufficient to confer a fully malignant
      phenotype to the leukaemic clone.

PMID- 9029019
TI  - Additional chromosome abnormalities confer worse prognosis in acute promyelocytic
      leukaemia.
AB  - Acute promyelocytic leukaemia (APL) has been associated with a favourable
      prognosis in many studies of acute myeloid leukaemia. A series of 54 patients
      treated at the Royal Marsden Hospital between 1979 and 1996, with APL and the
      t(15;17) chromosome translocation at presentation, was examined for the effect of
      additional chromosome abnormalities in their presentation karyotype on survival.
      The patients were aged between 2 and 62 years with a median age of 31 years.
      There were approximately equal numbers of males and females. Presentation white
      cell count ranged from O.7 to 156 x 10(9)/l with a median of 1.0 x 10(9)/l. 39%
      of patients (21/54) had additional chromosome abnormalities at presentation.
      Statistical analyses were performed for factors thought to influence survival
      such as age, sex, white cell count, and number of courses of chemotherapy
      required to enter remission. These showed that the presence of additional
      chromosome abnormalities has an adverse effect on prognosis, independent of other
      prognostic indicators, reducing it to the level of patients with AML from less
      favourable cytogenetic subgroups. These data indicate that additional therapeutic
      strategies may be required in patients with APL who demonstrate cytogenetic
      aberrations over and above the t(15;17) at presentation. The biological basis for
      the more aggressive nature of these cases remains to be determined.

PMID- 9029020
TI  - Disappearance of prognostic significance of histopathological grading of nodular
      sclerosing Hodgkin's disease for unselected patients, 1972-92.
AB  - The importance of the subclassification of nodular sclerosing Hodgkin's disease
      (NSHD) according to the British National Lymphoma Investigation Group (BNLI)
      criteria, which had an independent prognostic value for 90 unselected patients
      diagnosed in our region in the period 1972-83, is still equivocal. Because
      survival of patients with Hodgkin's disease improved in our region during the
      period 1972-92 and because treatment may modify prognostic factors, we re
      evaluated the prognostic value of NSHD subclassification up to 1993. A registry
      based study was performed with data on all 345 Hodgkin patients diagnosed in the
      period 1972-92. Available histology was reviewed. The prognostic value of nodular
      sclerosis (NS) grading was evaluated for two periods, 1972-80 and 1981-92,
      designated as the seventies and the eighties, respectively. NSHD was diagnosed in
      57% (n = 195) of all registered cases of Hodgkin's disease, 17 of which could not
      be evaluated. NS stage I (NSI; 73%) and NS stage II (NSII; 27%) patients
      exhibited the same distribution of stage during both periods; NSII patients were
      older than NSI patients in the seventies. NSII patients presented with an
      elevated ESR and B symptoms more frequently during the eighties and subsequently
      received combined modality therapy more often. The crude 5-year survival rate for
      grade I v grade II NSHD was 85% v 38% (P < 0.05) for the seventies and 84% v 83%
      for the eighties. Subclassification of NSHD was not an independent prognostic
      factor after adjustment for age, stage, gender, B symptoms and ESR, though it
      remained of independent prognostic value when ESR was left out of the Cox model.
      The most important factors adversely influencing survival were advanced age,
      advanced stage and male gender. The independent prognostic value of the
      subclassification of NSHD has disappeared, as reflected by the clearly improved
      survival of NSII patients, probably due to more intensive treatment in the
      eighties, whereas survival of NSI patients did not changes.

PMID- 9029021
TI  - Paclitaxel activity for the treatment of non-Hodgkin's lymphoma: final report of
      a phase II trial.
AB  - In order to determine the activity of paclitaxel in patients with relapsed or
      refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II clinical trial
      in which eligible patients received paclitaxel 200 mg/m2 intravenously over 3 h.
      Treatment was repeated every 3 weeks. Patients achieving complete or partial
      responses after two courses of paclitaxel continued to receive therapy for a
      maximum of eight courses, otherwise they were removed from the study. Of 96
      evaluable patients, 45 (47%) had primary refractory disease, and 51 (53%) had
      relapsed lymphoma. The median number of prior treatment regimens was two (range
      one to 10 regimens). 45 patients had lowgrade, 44 had intermediate-grade, and
      seven had mantle cell lymphoma. 24/96 patients responded (10 complete and 14
      partial remissions) for an overall response rate of 25% (95% CI 17-35%). Patients
      with relapsed lymphoma had a higher response rate than those with primary
      refractory disease (19/51 = 37% v 5/45 = 11%; P < 0.01), and patients with
      relapsed intermediate-grade lymphoma had a higher response than those with
      relapsed low-grade lymphoma (9/18 = 50% v 10/31 = 32%; P = 0.22). The treatment
      was very well tolerated with the most common side-effects being alopecia (100%),
      peripheral neuropathy (35% of > or = grade II), and arthralgia/myalgia (25% of >
      or = grade II). After the first course of paclitaxel, grade III/IV
      thrombocytopenia and neutropenia were observed in 21% and 23% of the patients
      respectively. 23 episodes of neutropenic fever developed after 250 courses of
      paclitaxel therapy (8%). We conclude that paclitaxel, at this dose and schedule,
      is an active new drug for the treatment of non-Hodgkin's lymphoma. The activity
      of paclitaxel combination programmes are currently under investigation.

PMID- 9029022
TI  - Conventional induction treatments do not influence overall survival in multiple
      myeloma.
AB  - A retrospective analysis was performed on two subsequent myeloma patient series
      treated with the same conventional induction treatments, melphalan and prednisone
      or alternating VMCP/VBAP: 273 were enrolled in the multicentre M83 trial (M83
      trial group) from 1983 to 1986; 160 were referred to a single institution
      (Haemat. To group) from 1986 to 1994. Response to treatment was very similar in
      the two groups (53% v 50.3%). Remission duration curves merely overlapped (median
      20 v 21 months). However, overall survival was significantly longer in the
      Haemat. To group (43.2 v 33 months, P < 0.04). This difference was due to a
      prolonged period from relapse or progression to death (21 v 8 months, P < 0.01;
      20.8 v 7 months, P < 0.009). Prolonged survival was also observed in poor
      prognosis patients with a serum beta2-microglobulin level > 3 mg/l, in the
      Haemat. To group (31.8 v 24.2 months, P < 0.04). The same induction treatments
      produced almost identical response rate and remission duration in both groups,
      but overall survival was 10 months longer for one group. However, it could be
      argued that treatment salvage modalities and support therapies have been improved
      in a decade. Lastly, induction treatments did not influence overall survival.

PMID- 9029023
TI  - Idiotype-specific T lymphocytes in monoclonal gammopathies: evidence for the
      presence of CD4+ and CD8+ subsets.
AB  - Tumour-specific CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells may
      participate in the control and eradication of tumour cells. In the present study,
      idiotype-specific stimulation of CD4+ and CD8+ blood T cells from patients with
      monoclonal gammopathy of undetermined significance and patients with untreated
      multiple myeloma stage I was examined. Activation was measured in the CD4+ and
      CD8+ subsets enriched by magnetic microbeads as the incorporation of 3H-thymidine
      and the secretion of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 by
      single cells using the enzyme-linked immunospot assay. Idiotype-specific T cells
      were found in four of seven patients. Stimulation was mainly confined to the CD4+
      subset in three of the four responding patients. This type of response was major
      histocompatibility complex (MHC) class II restricted as it could be inhibited by
      monoclonal antibodies against MHC class II (HLA-DR), but not against class I (HLA
      ABC) molecules. Idiotype-specific CD8+ T cells were also demonstrated in these
      patients although at a lower frequency. One patient showed a strong and
      dominating activation of CD8+ T cells which could be blocked by antibodies
      against HLA-ABC but not against HLA-DR. Idiotype-specific CD4+ or CD8+ T cells
      were mainly of the type-1 subsets as judged by their secretion of IFN-gamma and
      IL-2. Thus, this study provides evidence for the presence of idiotype-specific
      and MHC-restricted CD4+ and CD8+ T cells of the type-1 subsets in patients with
      monoclonal gammopathies. Such T cells with the potential to control the growth of
      tumour B cells may be a suitable target for immunotherapeutic interventions in
      patients.

PMID- 9029024
TI  - A low but functionally significant MDR1 expression protects primitive
      haemopoietic progenitor cells from anthracycline toxicity.
AB  - Pgp is expressed on normal haemopoietic progenitor cells. The significance of the
      efflux pump in protecting normal progenitors for anthracycline toxicity is not
      defined and is the subject of this study. Pgp was measured in CD34+ progenitors
      with a rhodamine efflux assay. A high efflux, modulated by verapamil, was only
      found in a distinct subpopulation (20-30%). Pgp measured by the monoclonal
      antibody antibody (MoAb) MRK-16 was low in the rhodamine dull, but significantly
      (P < 0.04) higher than in the rhodamine bright cells. Reverse transcriptase
      polymerase chain reaction (RT-PCR) of MDR1 mRNA showed a very weak signal in both
      populations. In a single-cell clonogenic assay, rhodamine dull cells appeared
      less sensitive to anthracyclines (IC50 daunorubicin 0.005 microg/ml; adriamycin
      0.03 microg/ml) compared to rhodamine bright cells (IC50 daunorubicin 0.0025
      microg/ml; adriamycin 0.01 microg/ml). Furthermore, verapamil significantly (P <
      0.05) potentiated anthracycline toxicity only in the rhodamine dull cells,
      proving its Pgp-specific modulating effect. Rhodamine dull cells gave larger and
      more mixed colonies compatible with a more primitive origin. Although detection
      with MoAbs and RT-PCR revealed a low Pgp level, functionally this Pgp appeared to
      be very important in protecting primitive progenitors against anthracycline
      toxicity. This protection can be jeopardized by administration of Pgp modulators.

PMID- 9029025
TI  - P-glycoprotein (PGP) and lung resistance-related protein (LRP) expression and
      function in leukaemic blast cells.
AB  - P-glycoprotein (PGP) lung resistance protein (LRP) and multidrug resistance
      associated protein (MRP) expressions and function were evaluated by flow
      cytometry in 65 leukaemic patients (38 acute non-lymphocytic leukaemias, eight
      acute lymphocytic leukaemias, 19 Ph-positive chronic myeloid leukaemias in
      blastic phase). By using the MRK-16, the LRP-56 and the MRPm6 MoAbs, 34% of the
      cases did not over-express any proteins (-); 24.5% over-expressed (+) only PGP,
      11% only LRP, 1.5% only MRP, 24.5% both PGP and LRP, and 4.5% both PGP and MRP.
      The mean intracellular daunorubicin accumulation (IDA) and rhodamine 123 (Rh123)
      retention in the presence or absence of the reversal agent SDZ PSC 833 (PSC) of
      the PGP-/LRP-/MRP- cases were comparable to the ones observed in normal
      leucocytes. With respect to the non-over-expressing cases, the PGP-/LRP+/MRP-
      cases showed only an impaired IDA (mean 204 +/- 29; P < 0.001). The PGP+/
      LRP+/MRP- cases had a defect both in IDA (mean 166 +/- 47, P < 0.001) and Rh123
      retention (mean 0.42 +/- 0.14: P < 0.001), which were both corrected by PSC. All
      the PGP+/LRP+/MRP- cases had a defect in IDA (mean daunorubicin (DNR)
      accumulation 192 +/- 44; P < 0.001). However, only in 8/16 of them an evident
      defect in Rh123 retention was found. In conclusion, both PGP and LRP over
      expression were common in leukaemia. An impaired IDA was found in all cases over
      expressing PGP, LRP or both. The study of Rh123 retention could give incorrect
      information about the blast cells' ability to accumulate cytotoxic drugs in
      patients over-expressing both PGP and LRP.

PMID- 9029026
TI  - Acute lymphoblastic leukaemia in childhood: cell proliferation without rest.
AB  - The percentage of non-cycling blast cells in children with untreated acute
      lymphoblastic leukaemia (ALL) was investigated by staining smears for statin, a
      nuclear protein specifically present in non-growing resting cells. Results were
      compared with purified normal CD34-positive progenitors. A low fraction of ALL
      and CD34-positive cells expressed statin (2.9 +/- 3.8% and 2.8 +/- 3.1%,
      respectively), the growth fraction assessed by staining for the nucleolar antigen
      p120 was 94% in both ALL and CD34-positive cell samples. From this analysis it
      can be concluded that the compartment of non-replicating cells in ALL as well as
      in normal CD34-positive precursor cells collected from peripheral blood is very
      small and that most cells are cycling.

PMID- 9029027
TI  - Hypereosinophilic syndrome in a child mosaic for a congenital triplication of the
      short arm of chromosome 8.
AB  - An 11-year-old boy with mental retardation, malformations, and the mosaic
      karyotype 47,XY,+i(8p)/46,XY presented with fever, headache and petechiae.
      Peripheral blood WBC was 190 x 10(9)/l; and contained > 90% mature eosinophils.
      Cytogenetic analysis of the eosinophils revealed no aberrations except the
      constitutional karyotype. The patient was diagnosed as having a hypereosinophilic
      syndrome. Shortly after initiation of therapy he died from extensive mural
      thrombi of the heart and thrombi of several other organs. This is the first case
      of congenital triplication of the short arm of chromosome 8 associated with
      hypereosinophilic syndrome, suggesting involvement of genes on chromosome 8p in
      the regulation of eosinopoiesis.

PMID- 9029028
TI  - A new c-kit mutation in a case of aggressive mast cell disease.
AB  - Systemic mast cell disease (SMCD) is a disorder characterized by a mast cell
      proliferation in various tissues. Mast cells express the c-kit proto-oncogene. A
      few cases of c-kit mutations have been described in SMCD. We report an aggressive
      SMCD in a patient who presented with a bone marrow infiltration by abnormal mast
      cells. Molecular studies of mast cell DNA and RNA revealed a new c-kit
      heterozygous mutation (Asp820Gly). This mutation leads to a drastic amino-acid
      change and is located close to the highly oncogenic Asp816Val. These findings
      suggest that the Asp820Gly has a potential role in c-kit activation.

PMID- 9029029
TI  - An antisense Bcr-Abl phosphodiester-tailed methylphosphonate oligonucleotide
      reduces the growth of chronic myeloid leukaemia patient cells by a non-antisense
      mechanism.
AB  - The specificity of antisense oligonucleotides targeted to the mRNA breakpoint
      region of the Bcr-Abl oncogene, found in leukaemic cells from patients with
      chronic myeloid leukaemia, remains controversial due to non-specific effects. To
      prevent protein binding of oligonucleotides we designed and tested a
      methylphosphonate oligonucleotide with an attached 3' soluble phosphodiester
      tail. Growth of chronic myeloid leukaemia (CML) cell lines BV173, KCL-22 and
      cells of CML patients tested was inhibited by the b2a2 type antisense Bcr-Abl
      oligonucleotide and not with controls. Also the growth of control CD34+ cells of
      two healthy donors, control cell lines and cells from AML patients was only
      moderately affected or not affected. Bcr-Abl protein studies in combination with
      growth-determination experiments indicated that the antisense methylphosphonate
      Bcr-Abl oligonucleotide tested is a potent inhibitor of the growth of CML cells
      but works in a non-antisense manner.

PMID- 9029030
TI  - Long-term follow-up of leukaemia patients after related cryopreserved allogeneic
      bone marrow transplantation.
AB  - We have previously shown that allogeneic bone marrow transplantation (BMT) with
      cryopreserved donor marrow cells can be used without prolonging the engraftment
      time or interfering with the reconstitution of haemopoiesis. In this report we
      extend our initial observations of the first 40 patients who underwent allogeneic
      bone marrow transplantation from related donors with cryopreserved donor bone
      marrow for haematological malignancies, including the long-term follow-up data of
      the previously reported patients. The outcome of these patients was compared with
      that of 40 related BMT recipients receiving fresh donor bone marrow (historic
      control group). Time until engraftment of all patients receiving cryopreserved
      bone marrow was not different from the control group (ANC > 0.5 x 10(9)/l 17d
      (range 11-24 d) versus 17.5 d (range 10-28 d): platelets > 20 x 10(9)/l 21 d
      (range 11-85 d) versus 22 d (range 13-69 d), respectively). There was the same
      incidence of acute and chronic GvHD in patients receiving either cryopreserved
      bone marrow or fresh bone marrow (acute GvHD > or = II 61% v 60% and chronic GvHD
      56% v 52%, respectively). Chimaerism studies showed no difference between the
      patient groups. Furthermore, the two groups did not differ in day 100 survival
      (82% v 72%). With a median follow-up of 520 d (range 47-1365 d) and 1289 d (range
      48-1849 d), 60% of the patients receiving cryopreserved and 53% of the patients
      receiving fresh allogeneic donor bone marrow, respectively, are alive. We
      conclude that cryopreservation of allogeneic related donor bone marrow does not
      adversely affect engraftment, does not decrease the incidence of severe acute
      GvHD, and does not seem to affect the day 100 survival or long-term haemopoiesis.

PMID- 9029031
TI  - Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood
      acute lymphoblastic leukaemia in first remission. Associazione Italiana di
      Ematologia ed Oncologia Pediatrica (AIEOP) and the Gruppo Italiano Trapianto di
      Midollo Osseo (GITMO).
AB  - We compared the outcome of children with high-risk acute lymphoblastic leukaemia
      (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO)
      or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All
      children treated by the Italian Paediatric Haematology Oncology Association for
      HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children
      were given BMT at a median of 4 months from first CR, with preparative regimens
      including total-body irradiation (n = 25/30). 130 matched controls for BMT
      patients were identified among 397 HR-ALL CHEMO patients. Matching on main
      prognostic factors and duration of first CR was adopted to control the selection
      and time-to-transplant biases. The comparative analysis was based on the results
      of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6
      months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77)
      and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the
      two groups (P = 0.34). With a median follow-up of 4 years, the disease-free
      survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO
      group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of
      BMT patients. In the BMT group the estimated cumulative incidence of relapse at
      1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in
      the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence
      continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results
      of this study suggest that, with respect to the CHEMO group, the higher risk of
      early failure in the BMT group is outweighed by the lower risk of relapse after 1
      year. Results prompt the need for a prospective study, in order to demonstrate
      the likely advantage of BMT in HR childhood ALL in first CR.

PMID- 9029032
TI  - PCR-positivity in harvested bone marrow predicts relapse after transplantation
      with autologous purged bone marrow in children in second remission of precursor B
      cell acute leukaemia.
AB  - Purging of autologous bone marrow (BM) grafts of children in second remission
      after a relapse of precursor B acute lymphoblastic leukaemia (ALL) in the BM has
      been carried out in our laboratory since 1987, initially by complement mediated
      cell lysis. This protocol was extended by performing an immunorosette depletion
      before lysis with complement. The aim of the present study was to assess by
      polymerase chain reaction the presence of residual leukaemic cells in the BM
      grafts before and after purging. The results were then correlated to clinical
      outcome. In 24/28 patients a PCR product was obtained by amplification of IgH
      and/or TcR junctional regions. BM before purging was available for analysis in 13
      patients. We found that leukaemic cells could be detected in 8/13 (62%) of these
      grafts before purging . All these eight patients experienced a relapse,
      regardless of whether the purging procedure had been successful (defined as
      achievement of PCR-negativity) or not. In contrast, none of the five patients
      with PCR-negative grafts before purging relapsed (P = 0.0008). One patient died
      due to transplant-related toxicity. Of the remaining 23 patients, nine patients
      received a PCR-positive BM graft after purging. All these nine patients
      experienced a relapse as compared to 6/14 whose BM was PCR-negative after purging
      (P = 0.0072). Two of eight PCR-positive BM grafts could be purged to PCR
      negativity. Thus, improvements both in treatment of leukaemia and in purging
      efficacy are still needed.

PMID- 9029033
TI  - Persistence of residual tumour cells after cytokine-mediated ex vivo expansion of
      mobilized CD34+ blood cells in multiple myeloma.
AB  - Mobilized CD34+ blood cells were immunomagnetically enriched from leukapheresis
      products in five multiple myeloma (MM) patients. Thawed samples of selected CD34+
      cells were cultured for up to 21 d in a liquid and stroma-free culture system
      with different combinations of recombinant cytokines. The most successful cell
      expansion was obtained when a combination of rh-IL-1beta, rh-IL-3, rh-IL-6, rh
      SCF, rh-G-CSF and rh-GM-CSF was used. After 14 d this mixture gave a 120-187-fold
      overall increase of total nuclear cells and a 4-8-fold overall increase of early
      CFU-GM numbers. In four patients a very sensitive patient-specific PCR analysis
      showed the presence of monoclonal cells in the initial leukapheresis products.
      After immunomagnetic separation a tumour cell depletion of 2-4 logs was observed,
      although all samples still contained malignant cells. Cell suspensions that were
      cultured with the most potent cytokine combination showed tumour contamination in
      two-thirds of evaluable cases at the moment of maximal CFU-GM output. Serial cDNA
      dilution experiments indicated that the positive PCR results at day 14 reflected
      the persistence of pre-culture tumour cells rather than in vitro expansion of
      tumour cells in two cases. This study demonstrates that ex vivo expansion of
      myeloid precursor cells from mobilized CD34+ cells in MM patients does not always
      result in an effective purging of residual tumour cells. On the other hand, our
      culture conditions do not seem to favour in vitro expansion of malignant cells,
      despite the use of a cytokine cocktail that includes potential myeloma growth
      factors.

PMID- 9029034
TI  - Human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus in organ transplant
      patients with immunosuppression.
AB  - Several recent studies have demonstrated Kaposi's sarcoma-associated herpes virus
      (KSHV), also known as putative human herpes virus-8 (HHV-8), DNA in various
      epidemiologic forms of Kaposi's sarcoma (KS), including AIDS-associated, classic,
      and endemic types. Risk of developing KS in non-HIV-infected immunosuppressed
      hosts, such as patients following solid organ transplantation, is also
      significantly higher compared to normal individuals. We have retrospectively
      evaluated 28 organ transplant patients with KS (23 cutaneous and five visceral)
      for the presence of KSHV genome by polymerase chain reaction (PCR) amplification
      of DNA isolated from formalin-fixed, paraffin-embedded archival tissue samples.
      27/28 KS patients were positive for the presence of KSHV. In four KS patients,
      tissue samples with no histologic evidence of KS were also analysed for KSHV. No
      evidence of positivity in three samples was noted, but one patient had weak
      positive amplification products on DNA samples isolated from a gastric biopsy
      with chronic gastritis and lymph node with sinus histiocytosis. These data
      support the association of KSHV with KS developing in non-HIV-infected
      immunosuppressed patients, similar to other forms of KS, and suggest that KSHV
      may play a significant role in the development of all forms of KS.

PMID- 9029035
TI  - Peripheral blood stem cell apheresis in normal donors: feasibility and yield of
      second collections.
AB  - We report 13 normal peripheral blood stem cell (PBSC) donors who had a second
      PBSC collection for allogeneic transplantation performed after the first. The
      median interval between the first and second collection was 5 months.
      Mobilization was achieved with filgrastim (12 microg/kg/d). No significant
      difference was found in the median pre-apheresis leucocyte count (x10(9)/l)
      between the two donations (40.2 v 38.5; P = 0.91). The median apheresis yield
      (x10(6) CD34+ cells/litre blood processed, first apheresis) was also similar (28
      v 27.3; P = 0.91). Filgrastim-related adverse events were comparable. These data
      suggest that second PBSC collections are feasible, similarly tolerated and
      provide comparable apheresis yields.

PMID- 9029036
TI  - Prospective randomized study comparing the efficacy of bioequivalent doses of
      glycosylated and nonglycosylated rG-CSF for mobilizing peripheral blood
      progenitor cells.
AB  - Thirty patients diagnosed with breast cancer were included in a prospective
      randomized study comparing the in vivo priming effect of bioequivalent doses of
      glycosylated (lenograstim) and nonglycosylated (filgrastim) rG-CSF
      administration. Analysis of the efficacy of equivalent biological doses of both
      rG-CSFs showed no significant differences either in the mobilization of the
      subpopulations of PBPC considered (CD34+, CD34+/38-, CD34+/DR-), the content of
      such CD34+ cell subsets in the leukapheresis product, or the cost of the
      mobilization and collection procedures between both recombinant molecules. These
      results suggest that priming with bioequivalent doses of the two commercially
      available forms of glycosylated or nonglycosylated rG-CSF has a similar in vivo
      effect on PBPC mobilization.

PMID- 9029037
TI  - Successful autografting in chronic myelogenous leukaemia using Philadelphia
      negative blood progenitor cells mobilized with rHuG-CSF alone in a patient
      responding to alpha-interferon.
AB  - Several non-randomized studies suggest a possible survival advantage for chronic
      myelogenous leukaemia (CML) patients treated with an autologous stem-cell
      transplantation. Due to the possible contribution of residual leukaemic cells
      present in the inoculum in post-transplant relapse, several methods are being
      evaluated to eliminate neoplastic cells or to select 'normal' (Ph1 negative)
      progenitor cells for autografting. Recently, several studies have shown that Ph1
      negative blood progenitor cells can be mobilized by rHuG-CSF alone in patients
      who have a cytogenetic response to alpha-interferon (IFN). We describe the first
      case, as far as we are aware, of a CML patient responding to IFN autografted by
      using blood progenitor cells collected by rHuG-CSF alone.

PMID- 9029038
TI  - Royal College of Physicians Consensus Conference on unrelated donor BMT: its use
      in leukaemias and allied disorders; 29-30 October 1996.

PMID- 9029039
TI  - Investigation of chronic hepatitis C infection in individuals with haemophilia.

PMID- 9029040
TI  - Mutations in the FVIII gene in seven families with mild haemophilia A.

PMID- 9029041
TI  - Hepatitis C virus infection (and additional neoplasms) among marginal zone
      lymphomas.

PMID- 9029043
TI  - Disposition and metabolism of tenidap in the rat.
AB  - Tenidap is a new antirheumatic drug currently undergoing clinical evaluation. It
      inhibits production and activity of cytokines in vivo and causes significant
      reductions in plasma markers of disease activity in rheumatoid arthritis. After
      the oral administration of C-14 labeled tenidap, bile, urine and plasma were
      examined by HPLC and atmospheric pressure tandem mass spectrometry. Label is
      excreted primarily in bile/feces and the remainder in urine, with good
      recoveries. Numerous metabolites were identified and the structures of most were
      confirmed by comparison with authentic synthetic samples. Hydroxylation in
      several positions on both the oxindole and thienyl rings of tenidap represents
      the major routes of metabolism; most of these metabolites are subsequently
      conjugated. The glucuronide of 5'-hydroxytenidap, excreted primarily in bile, is
      the major metabolite, constituting about one third of the oral dose recovered.
      Other pathways include dihydroxylation and methoxylation on the thienyl ring. An
      unusual reduction of hydroxytenidap took place, resulting in the formation of a
      novel thiolactone analog. Anaerobic incubation with rat cecal contents generated
      the thiolactone metabolite, suggesting the involvement of gut microflora.

PMID- 9029042
TI  - Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P4502C18
      and P4502C19 as low K(M) diazepam N-demethylases.
AB  - The present study provides a detailed kinetic analysis of diazepam metabolism by
      all four known members of the human P4502C subfamily expressed from their cDNAs
      in Escherichia coli. Both P4502C18 and P4502C19 were found to be low K(M)
      diazepam N-demethylases with apparent K(M) values of 24 +/- 4 microM and 21 +/- 3
      microM, respectively. These values closely resemble the low K(M) component of
      diazepam N-demethylase activity exhibited by human liver microsomes. In addition,
      P4502C19 also catalyzed diazepam 3-hydroxylation with a K(M) value of 21 +/- 9
      microM. Although P4502C8 was essentially inactive in catalyzing diazepam
      metabolism, P4502C9 catalyzed the N-demethylation with a relatively high K(M) of
      80 +/- 15 microM and an overall 3- to 6-fold lower catalytic efficiency, compared
      with P4502C18 and P4502C19, respectively. At a substrate concentration of 10
      microM, diazepam N-demethylation in a panel of human liver microsomes was
      inhibited 42 +/- 12% (mean +/- SD, N = 6) by a polyclonal anti-CYP2C antibody. In
      the same experiment, 3-hydroxylation remained unaffected (<10% inhibition). 1
      microM of the CYP3A inhibitor ketoconazole inhibited 37 +/- 19% of the N
      demethylation and 86 +/- 5% of 3-hydroxylation. Estimates of relative
      contributions to diazepam N-demethylation of P4502C9 (8 +/- 4%), P4502C18 (<2%),
      and P4502C19 (33 +/- 14%) and to diazepam 3-hydroxylation of P4502C19 (9 +/- 3%)
      based on the kinetic parameters of the recombinant enzymes and on specific
      contents of the individual 2C P450s determined in immunoblots are consistent with
      the inhibition data. In conclusion, these data confirm that both P4502C19 and
      P4503A are major contributors to human liver microsomal diazepam N-demethylation
      at low substrate concentrations, whereas P4503A is the major enzyme responsible
      for 3-hydroxylation.

PMID- 9029044
TI  - Comparison of in vitro carnitine and glycine conjugation with branched-side chain
      and cyclic side chain carboxylic acids in rats.
AB  - The substrate specificity for carnitine conjugation was examined using rat
      hepatocytes and kidney slices and compared with glycine conjugation which is a
      competitive pathway through the CoA thioester. For both hepatocytes and kidney
      slices, the best substrate for the camitine conjugate was cyclopropanecarboxylic
      acid followed by cyclobuthanecarboxylic acid (CBCA) and cyclohexanecarboxylic
      acid (CHCA). For the glycine conjugate, the best substrate was benzoic acid, with
      conjugation also occurring with CHCA and CBCA. These results suggest that
      carnitine transferase shows substrate specificity for cyclic side chain
      carboxylic acids of lesser carbon number, while glycine transferase shows inverse
      specificity. To compare directly the amounts of carnitine and glycine conjugates
      in the liver and the kidney, we estimated the endogenous amounts of carnitine and
      glycine and then multiplied the results by the production ratio of each
      conjugate. With respect to the enzyme activity per unit tissue weight, the kidney
      tended to show higher activities for both conjugates than the hepatocytes. This
      is the first report, to our knowledge, of the kidney having high carnitine
      conjugation activity. Cyclopentanecarboxylic acid (CPECA) was the least effective
      substrate for glycine and carnitine conjugates in both hepatocytes and kidney
      slices, CPECA may not readily undergo esterification with CoA. The branched-side
      chain carboxylic acids, such as pivalic acid (PA) and isobutylic acid, were also
      poor substrates for carnitine and glycine conjugates in rat hepatocytes and
      kidney slices.

PMID- 9029045
TI  - Comparative metabolism of the tobacco-related carcinogens benzo[a]pyrene, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanol, and N'- nitrosonornicotine in human hepatic microsomes.
AB  - We compared the metabolism in human hepatic microsomes of three tobacco smoke
      carcinogens believed to be involved in the induction of cancer in humans:
      benzo[a]pyrene (BaP),4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N'
      nitrosonomicotine (NNN). The metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL), a major metabolite of NNK, was also investigated. Although the
      metabolism of some of these compounds by human enzymes or tissue preparations has
      been previously examined in some studies, they have never been compared in the
      same human hepatic samples. Moreover, there have been no previous reports of NNAL
      metabolism by human tissues or enzymes. The tritium-labeled carcinogens (3
      microM) were incubated with 10 different human hepatic microsomal preparations
      and cofactors for 10-20 min, and the products were analyzed by radioflow HPLC.
      NNN was the best substrate for oxidative metabolism, with the 5'-hydroxylation
      pathway being the predominant one observed (mean +/- SD = 31 +/- 17 pmol/min/mg
      protein). alpha-Hydroxylation of NNK by the methylene and methyl hydroxylation
      metabolic activation pathways was the next fastest reaction, with rates of 3.1 +/
      1.9 and 3.3 +/- 1.1 pmol/min/mg protein, respectively. Metabolism of BaP
      resulted in the formation of dihydrodiols and phenols; trans-7,8-dihydro-7,8
      dihydroxy-BaP, its major proximate carcinogen, was formed at a rate of 1.1 +/-
      0.61 pmol/min/mg protein. alpha-Hydroxylation of NNAL proceeded at a rate of 0.53
      +/- 0.26 pmol/min/mg protein. The results of this study demonstrate that human
      hepatic microsomes metabolize all of these tobacco carcinogens resulting in a
      substantial stream of electrophilic intermediates capable of binding to DNA. The
      relative rates of oxidative metabolism to electrophiles or their precursors were
      NNN > NNK > BaP > NNAL. Correlation studies indicated involvement of cytochrome
      P4502A6 in the 5'-hydroxylation of NNN and cytochrome P4503A4 in the alpha
      methylene hydroxylation and pyridine-N-oxidation of NNK and NNAL. The results of
      this study provide the first data on the comparative metabolism of these
      important carcinogens in human hepatic microsomes.

PMID- 9029046
TI  - Induction of two UDP-glucuronosyltransferase isoforms sensitive to phenobarbital
      that are involved in morphine glucuronidation: production of isoform-selective
      antipeptide antibodies toward UGT1.1r and UGT2B1.
AB  - We document here in that two UDP-glucuronosyltransferase (UGT) isoforms sensitive
      to phenobarbital are involved in morphine glucuronidation in Wistar and Sprague
      Dawley rats. The hepatic microsomal morphine UGT activity in untreated Gunn rats
      was significantly less than that of untreated Wistar rats. Although the morphine
      UGT activity in the liver of Gunn rats was increased by phenobarbital (PB)
      treatment, this was significantly less than that in the liver of PB-treated
      Wistar rats. UGT1.1r is an isoform of morphine UGT in rat, and UGT2B1 is also
      considered an isoform of morphine UGT, because UGT2B1 (stably expressed in V79
      cells) exhibited morphine UGT activity. We prepared specific antipeptide
      antibodies against UGT1.1r and UGT2B1. Using isoform-specific antipeptide
      antibodies, both UGT1.1r and UGT2B1 in Wistar and Sprague-Dawley rats were
      inducible by PB treatment. However, UGT1.1r is not present in the liver from Gunn
      rats. This study is the first demonstration that protein levels of two morphine
      UGT isoforms, UGT1.1r and UGT2B1, in the liver of Wistar and Sprague-Dawley rats
      are inducible by PB treatment.

PMID- 9029047
TI  - Effects of freezing, thawing, and storage of human liver samples on the
      microsomal contents and activities of cytochrome P450 enzymes.
AB  - Effects of freezing, thawing, and storage at room temperature of human liver
      samples on the contents and catalytic activities of individual forms of
      cytochrome P450 (P450 or CYP) were examined. The stability of liver genomic DNA
      was also investigated. There were no significant decreases in microsomal levels
      or catalytic activities of P450 enzymes by storage at -80 degrees C for 5 years.
      We then examined the effects of freezing/thawing of liver samples. Levels of P450
      forms were determined immunochemically and by the activities of typical drug
      oxidation reactions in liver microsomes of human samples, which were divided into
      two groups. One group of samples was thawed and kept at 25 degrees C for 6 hr and
      then frozen again and kept for 1 week at -80 degrees C. In the other group, liver
      microsomes were prepared at the same time (as those from the other group), but
      not thawed and refrozen. Thawing the liver samples and storage for 6 hr at 25
      degrees C decreased contents of total P450 by about 90% and activities of both
      NADH-ferricyanide and NADPH-cytochrome c reductases by about 80%. However, the
      decrease in b5 levels was only about 30%. Spectral studies of P450 suggested that
      thawing the liver samples and holding them at 25 degrees C produced inactive form
      P420. P450 proteins were detected by immunoblot analysis with or without thawing,
      but catalytic activities for individual P450s were decreased drastically by
      thawing and holding samples for 6 hr at 25 degrees C. Only 10% of tolbutamide
      methyl hydroxylation activity was present, and there was no detectable
      ethoxyresorufin O-deethylation activity in such microsomes after thawing and
      holding samples for 6 hr at 25 degrees C. Genomic DNA from human livers was also
      found to be degraded after the samples were thawing. These results suggested that
      thawing and holding the liver samples at 25 degrees C decreased the levels and
      activities of P450s in microsomes and that there are differences in stabilities
      in individual forms of P450 proteins. P450 proteins determined immunochemically
      do not always reflect P450-catalytic functions in human liver microsomes because
      of difficulties in obtaining fresh liver samples.

PMID- 9029048
TI  - Human NAD(P)H:quinone oxidoreductase induction in human hepatoma cells after
      exposure to industrial acrylates, phenolics, and metals.
AB  - Induction of the endogenous human NAD(P)H:quinone oxidoreductase (HQOR1) gene in
      the human hepatoma cell line HepG2 was measured at both the enzyme activity and
      RNA levels after exposure to a variety of industrial compounds. An RNA probe was
      designed that was complementary to portions of both the coding region and the 3'
      nontranslated region unique to the largest (2.7-kilobase) HQOR1 transcript.
      Induction by three strong inducers of HQOR1 verified the utility of the antisense
      RNA probe. Ten industrial chemicals were evaluated as potential inducers, i.e.
      acrylonitrile, Sb2O3, BaO, CdCl2, CuCl, ethyl acrylate, methyl acrylate, MoO3,
      phenol, and toluene. Induction at the RNA level was about 2-fold higher than at
      the enzyme activity level except in the case of acrylonitrile, for which
      induction at the enzyme activity and RNA levels was similar. There was no
      preferential induction of the 2.7-kilobase transcript for any chemical tested,
      including 2,3,7,8-tetrachloro-dibenzo-p-dioxin, which had previously been
      reported to preferentially induce this transcript. Six of the 10 industrial
      chemicals, including four previously untested chemicals (phenol, Sb2O3, CuCl, and
      MoO3), were found to induce the HQOR1 gene. By comparison, previous studies in
      rodent systems failed to accurately predict the human HQOR1 gene response. Two
      chemicals previously shown to be inducers in rodent systems (methyl acrylate and
      CdCl2 failed to induce the HQOR1 gene. These results emphasize the importance of
      analyzing induction of the endogenous human gene, rather than simply
      extrapolating from rodent systems or gene fusion experiments.

PMID- 9029049
TI  - Short-term oral 3-hydroxypyridin-4-one dosing increases aluminum excretion and
      partially reverses aluminum-induced toxicity in the rabbit independent of
      chelator lipophilicity.
AB  - The objectives of the present study were to determine the efficacy and toxicity
      of repeated oral administration of 3-hydroxypyridin-4-one (HP) chelators in a
      rabbit model of aluminum (Al) accumulation and toxicity, and the influence of
      chelator lipophilicity on these effects. Efficacy was assessed as chelator
      induced Al mobilization and excretion and reversal of Al accumulation and Al
      induced toxicity. Chelator-induced toxicity was assessed by multiple measures.
      Six HPs were given orally 12 times over 1 month to Al-loaded rabbits, which had
      significant elevation of Al in most tissues and evidence of Al-induced
      nephrotoxicity, osteomalacia, and anemia. Intravenous desferrioxamine (DFO), the
      current chelator of choice for the treatment of Al-overload and toxicity, was
      included as a positive control. All six HPs and DFO demonstrated efficacy
      evidenced by significantly greater urinary and biliary Al elimination after the
      twelfth dose than seen in saline-treated controls. All of the HPs were more
      effective than DFO. Chelator-induced urinary Al excretion accounted for 58-98% of
      total (urinary plus biliary) Al excretion. Chelator-facilitated Al excretion was
      nearly complete within 12 hr, demonstrating a fairly short duration of action in
      rabbits with intact renal function. HP treatments did not consistently affect
      tissue concentrations of Al or other metals. However, there was a trend toward
      chelator-induced reduction of Al-induced nephrotoxicity. The influence of HP
      lipophilicity was limited to a positive correlation between HP x Al lipophilicity
      and biliary Al output and a negative correlation between HP and HP x Al
      lipophilicity and reduction of Kupffer cell Al. Little toxicity was evident after
      repeated oral HP dosing. Adrenal weight increased after treatment with several
      HPs. There was a decrease in testes weight after several HPs, which is consistent
      with an antiproliferative effect. More frequent dosing and/or a longer duration
      of HP treatment might produce greater reversal of the Al-induced toxicity and
      perhaps reveal more adverse effects than seen in this study. There was a lack of
      profound toxicity during this short-term study. The 1,2-dimethyl (CP20) and 1,2
      diethyl (CP94) HPs, which have been the most extensively studied HPs, were the
      least effective of the HPs examined. These results encourage the further
      investigation of other HPs as oral alternatives to DFO for the treatment of Al
      accumulation and toxicity.

PMID- 9029050
TI  - In vivo, ex vivo, and in vitro effects of L-NAME and L-arginine on the metabolism
      of theophylline in the rabbit.
AB  - It has been shown that selected isoforms of cytochrome P450 (P450) can generate
      nitric oxide from L-arginine analogs; however, the effect of L-arginine analogs
      on the catalytic activity of P450 remains unknown. To assess the effect of N
      nitro-L-arginine methyl ester (L-NAME; 25 mg/kg) and L-arginine (150 mg/kg) on
      the activity of P450, these compounds were administered intravenously every 8 hr
      for 2 days to groups of six New Zealand rabbits. Thereafter, the
      biotransformation of theophylline was documented in vivo (2.5 mg/kg i.v.) and ex
      vivo in hepatocytes of control and treated animals. In vivo, compared with
      control rabbits, both L-NAME and L-arginine increased theophylline plasma
      concentrations secondary to a reduction in theophylline systemic clearance by 46%
      and 42% (p < 0.05), respectively. Ex vivo, the effect of L-arginine analogs on
      P450 activity was documented by measuring the production of 3-methylxanthine
      (3MX), 1-methyluric acid (1MU), and 1,3-dimethyluric acid (1,3DMU) after
      incubation of theophylline (176 microM) with hepatocytes for 4 hr. L-NAME reduced
      the formation of 3MX, 1MU, and 1,3DMU by 42%, 45%, and 32% (p < 0.05),
      respectively. However, L-arginine reduced only the formation of 3MX by 34% (p <
      0.05). In the in vitro studies, incubation of L-NAME or L-arginine with
      hepatocytes did not modify the biotransformation of theophylline. It is concluded
      that L-NAME and L-arginine inhibit the activity of several apoenzymes of P450,
      the probable mechanism being a catalysis-dependent inhibition.

PMID- 9029051
TI  - Co-oxidative metabolism of 4-aminobiphenyl by lipoxygenase from soybean and human
      term placenta.
AB  - ]4-aminobiphenyl (4-ABP) co-oxidation catalyzed by the human term placental
      lipoxygenase (HTPLO), purified by affinity chromatography, was studied in the
      presence of linoleic acid (LA). Soybean lipoxygenase (SLO) which is extensively
      employed as a model lipoxygenase, was used for comparison. Spectral analyses of
      reaction media containing 4-ABP, LA, and SLO/HTPLO suggested the disappearance of
      substrate (deltaA at 270 nm) and a gradual appearance of a new peak at 315 nm,
      indicating a metabolite formation. Under optimal assay conditions, SLO exhibited
      a specific activity of 350 nmoles of 4-ABP depleted/min/nmole of enzyme. To
      observe the maximal rate of co-oxidation by the HTPLO (45 nmoles of 4-ABP
      depleted/min/mg protein), an incubation of 50 microM 4-ABP, 2 mM LA, and 80
      microg/ml protein at pH 7.4 was essential. 4-ABP was also oxidized by SLO in the
      presence of H2O2, although at a lower rate. The reversed-phase HPLC analysis of
      organic extracts of the incubations of 4-ABP with SLO and H2O2/LA as well as
      HTPLO and LA showed the formation of a major peak which was identified by GC-MS
      as 4,4'-azobis(biphenyl). The addition of GSH, BHT, and BHA to the enzymatic
      incubations decreased the formation of 4-ABP metabolite, suggesting the
      generation of a free radical as the initial metabolite during 4-ABP oxidation.
      Both the SLO and HTPLO mediated reactions were significantly inhibited by
      nordihydroguaiaretic acid, gossypol, and 5,8,11-eicosatriynoic acid.
      Collectively, these results suggest that the co-oxidation catalyzed by HTPLO may
      be the underlying biochemical mechanism responsible for the transplacental
      toxicity of 4-ABP.

PMID- 9029052
TI  - Metabolism and excretion of the novel antipsychotic drug ziprasidone in rats
      after oral administration of a mixture of 14C- and 3H-labeled ziprasidone.
AB  - The metabolism and excretion of ziprasidone (5-[2-[4-(1,2-benzisothiazol-3
      yl)piperazin-1-yl]ethyl]-6-++ +chloroindolin-2-one hydrochloride hydrate) were
      studied in Long Evans rats after oral administration of a single dose of a
      mixture of 14C- and 3H-labeled ziprasidone. The radioactive dose was
      quantitatively recovered over 7 days in both male and female rats. The percentage
      of the dose excreted in urine, bile, and feces of rats was 21.6, 19.2, and 55.6%,
      respectively. The total excretion in urine and bile suggested that at least 41%
      of the drug was absorbed. Absorption of ziprasidone was rapid, and the mean
      plasma concentrations of the unchanged drug and metabolites were slightly higher
      in the female rats than in the males. The maximal plasma concentrations for
      ziprasidone and metabolites were reached at 1 hr in both male and female rats.
      Based on AUC (0-12 hr) values, approximately 59 and 52% of the circulating
      radioactivity (average of 14C and 3H) was attributable to metabolites in male and
      female rats, respectively. Ziprasidone was extensively metabolized in rats, and
      only a small amount of ziprasidone was excreted as unchanged drug. Twelve
      metabolites were identified by ion spray LC/MS, using a combination of parent ion
      and product ion scanning techniques. The structures of eight metabolites were
      unambiguously confirmed by coelution on HPLC with synthetic standards, and four
      additional metabolites were partially identified. There was a gender-related
      difference in the excretion of urinary metabolites in Long Evans rats. The major
      route of metabolism in male rats involved N-dealkylation. In female rats the
      major metabolites were due to oxidation at the benzisothiazole ring. Based on the
      structures of these metabolites, four major and two minor routes of metabolism of
      ziprasidone were identified. The major routes included 1) N-dealkylation of the
      ethyl side chain attached to the piperazinyl nitrogen, 2) oxidation at the
      sulfur, resulting in the formation of sulfoxide and sulfone, 3) oxidation on the
      benzisothiazole moiety (other than sulfur), and 4) hydration of the C==N bond and
      subsequent oxidation at the sulfur of the benzisothiazole moiety. The minor
      routes involved N-oxidation on the piperazine ring and hydrolysis of the oxindole
      moiety.

PMID- 9029053
TI  - A comparative investigation of 2-propyl-4-pentenoic acid (4-ene VPA) and its
      alpha-fluorinated analogue: phase II metabolism and pharmacokinetics.
AB  - An earlier study in rats revealed that alpha-fluorination of 2-propyl-4-pentenoic
      acid (4-ene VPA), a toxic metabolite of the anticonvulsant drug valproic acid,
      would avert its metabolism via beta-oxidation and eliminate the drug-related
      hepatotoxicity. This investigation was carried out to compare 4-ene VPA and the
      alpha-fluorinated analogue (alpha-fluoro-4-ene VPA) for their pharmacokinetic and
      protein binding properties. Male Sprague-Dawley rats were dosed with either 4-ene
      VPA or alpha-fluoro-4-ene VPA i.p. at 1.4 mmol/kg. Blood was collected from the
      tail vein at various time points and serum samples were prepared. Urine was
      collected for 24 hr. A second set of rats was treated the same but sacrificed 1
      hr post dose, and the livers were homogenized in a Tris-buffer. Protein binding
      was assessed via ultrafiltration of the naive serum samples spiked with either of
      the drugs. The serum drug concentration-time profiles of 4-ene VPA and alpha
      fluoro-4-ene VPA seemed to resemble one another during the initial 200 min within
      which differences were reported for their effects on mitochondrial GSH. A second
      serum peak concentration was observed for 4-ene VPA at approximately 300 min,
      which was attributed to the extensive glucuronidation of the drug and
      enterohepatic circulation. The alpha-fluoro-4-ene VPA, on the other hand, did not
      show these properties with its major phase II metabolite being the corresponding
      L-glutamine conjugate. The toxic metabolite (E)-2-propyl-2,4-pentadienoic acid
      and its N-acetylcysteine conjugate were detected only in 4-ene VPA treated rats.
      Liver concentrations of 4-ene VPA and alpha-fluoro-4-ene VPA were 0.96 +/- 0.11
      and 0.89 +/- 0.19 micromol/g of wet liver, respectively, at 1 hr after the dose.
      Comparable and parallel serum free drug levels were apparent for the two drugs
      over a concentration range of 0.25 to 2.9 micromol/ml. Taken together, the data
      seem to suggest that the reported distinction in the ability of 4-ene VPA and
      alpha-fluoro-4-ene VPA to produce liver toxicity in the rat resides in
      differences in their metabolism rather than in their pharmacokinetic properties.

PMID- 9029054
TI  - Metabolism of the human immunodeficiency virus type 1 reverse transcriptase
      inhibitor delavirdine in rats.
AB  - Delavirdine mesylate (U-90152T) is a highly specific nonnucleoside reverse
      transcriptase inhibitor currently under development for the treatment of AIDS.
      The excretion, disposition, and metabolism of delavirdine were investigated in
      Sprague-Dawley rats after oral administration of [14C]delavirdine mesylate at
      single doses ranging from 10 to 250 mg/kg and multiple doses ranging from 20 to
      250 mg/kg/day. Excretion studies showed that feces was the major route of
      elimination, delavirdine was well absorbed (>80%) after a 10 mg/kg single dose,
      and excretion was dose-dependent. The metabolism of delavirdine in the rat was
      extensive. The following metabolites were identified (% of dose in rats given 10
      and 100 mg/kg, respectively): 6'-hydroxy delavirdine (7.1% and 15.6%) and its
      glucuronide (12.2% and 6.2%) and sulfate (5.5% and 3.2%) conjugates, despyridinyl
      delavirdine (12.1% and 11.7%) and its conjugate (13.0% and 11.7%), desalkyl
      delavirdine (16.5% and 13.4%), and its N-sulfamate, 6'- and 4'-sulfate conjugates
      (2.9% and 3.9%). Cleavage of the amide bond in delavirdine to give N
      isopropylpyridinepiperazine and indole carboxylic acid constituted a minor
      pathway. Degradation of 6'-hydroxy delavirdine generated despyridinyl delavirdine
      and the pyridine-ring opened MET-14. The metabolic pathway of delavirdine
      involved N-desalkylation, pyridine ring hydroxylation, pyridine ring cleavage,
      and amide bond cleavage.

PMID- 9029055
TI  - Metabolic inactivation of cytochrome P4502B1 by phencyclidine: immunochemical and
      radiochemical analyses of the protective effects of glutathione.
AB  - Phencyclidine (PCP) inactivates the 7-ethoxy-4-trifluoromethylcoumarin O
      deethylase activity of P4502B1 in a reconstituted system containing NADPH
      cytochrome P450 (P450) reductase (reductase) and L-alpha-phosphatidylcholine,
      dilauroyl in a time-, concentration-, and NADPH-dependent manner. Catalytic
      activity of the enzyme could not be restored upon reconstitution with fresh
      reductase, indicating that the effect was on the P450 and not on the reductase.
      Although the kinetics suggested that PCP would be classified as a classical
      mechanism-based inactivator, protection against inactivation of P450 by PCP by
      the presence of an exogenous nucleophile, such as glutathione (GSH), indicated
      otherwise. There was no loss of spectrally detectable P450 associated with
      inactivation either in the presence or absence of GSH. When radiolabeled PCP was
      used to inactivate the enzyme and the reaction mixture analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, radioactivity was found to be
      associated with P450, reductase, and catalase that had been added to protect
      against oxidative damage. When GSH was included in the reaction mixtures,
      analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      demonstrated a marked decrease in the binding to all three proteins.
      Correspondingly, analysis of the components of the inactivated sample by reversed
      phase HPLC demonstrated that radioactivity was associated with P450, reductase,
      and catalase, and that there was a marked decrease in the labeling of all three
      proteins in the presence of GSH. The stoichiometry of binding of radiolabeled PCP
      to the proteins in the incubation mixture in the absence of GSH was 4:1. In the
      presence of GSH, no significant amount of radioactivity was incorporated into the
      proteins. An anti-PCP metabolite antibody was used to detect PCP metabolite
      adducts bound to the inactivated enzyme by Western blot analysis. The antibody
      recognized adducts bound to P450, reductase, and catalase. In the presence of
      GSH, there was a decrease in immunoreactivity, although binding of PCP to all
      three proteins was still detected. Because the added nucleophile protects against
      inactivation and protein labeling by PCP, these data suggest that the reactive
      intermediate may escape from the active site and attack other sites on the P450,
      as well as other proteins in the milieu.

PMID- 9029057
TI  - Selective biotransformation of the human immunodeficiency virus protease
      inhibitor saquinavir by human small-intestinal cytochrome P4503A4: potential
      contribution to high first-pass metabolism.
AB  - Saquinavir is a HIV protease inhibitor used in the treatment of patients with
      acquired immunodeficiency syndrome, but its use is limited by low oral
      bioavailability. The potential of human intestinal tissue to metabolize
      saquinavir was assessed in 17 different human small-intestinal microsomal
      preparations. Saquinavir was metabolized by human small-intestinal microsomes to
      numerous mono- and dihydroxylated species with K(M) values of 0.3-0.5 microM. The
      major metabolites M-2 and M-7 were single hydroxylations on the octahydro-2-(1H)
      isoquinolinyl and (1,1-dimethylethyl)amino groups, respectively. Ketoconazole and
      troleandomycin, selective inhibitors of cytochrome P4503A4 (CYP3A4), were potent
      inhibitors for all oxidative metabolites of saquinavir. The cytochrome P450
      selective inhibitors furafylline, fluvoxamine, sulfaphenazole, mephenytoin,
      quinidine, and chlorzoxazone had little inhibitory effect. All saquinavir
      metabolites were highly correlated with testosterone 6beta-hydroxylation and with
      each other. Human hepatic microsomes and recombinant CYP3A4 oxidized saquinavir
      to the same metabolic profile observed with human small-intestinal microsomes.
      Indinavir, a potent HIV protease inhibitor and a substrate for human hepatic
      CYP3A4, was a comparatively poor substrate for human intestinal microsomes and
      inhibited the oxidative metabolism of saquinavir to all metabolites with a Ki of
      0.2 microM. In addition, saquinavir inhibited the human, small-intestinal,
      microsomal CYP3A4-dependent detoxication pathway of terfenadine to its alcohol
      metabolite with a Ki value of 0.7 microM. These data indicate that saquinavir is
      metabolized by human intestinal CYP3A4, that this metabolism may contribute to
      its poor oral bioavailability, and that combination therapy with indinavir or
      other protease inhibitors may attenuate its low relative bioavailability.

PMID- 9029056
TI  - Comparison of stably expressed rat UGT1.1 and UGT2B1 in the glucuronidation of
      opioid compounds.
AB  - Opioids are important drugs used as analgesics, antitussives, antidiarrheals, and
      in the therapy of myocardial infarctions, and as antagonists of opioid
      intoxication. The glucuronidation of these compounds, catalyzed by UDP
      glucuronosyltransferases (UGTs), is well known to be a primary step in their
      metabolism to hydrophilic products and in their ultimate excretion. The present
      study was designed to compare the reactivity and relative glucuronidation
      efficiencies of opioid agonists, antagonists, and partial agonists with two rat
      UGT isoforms; UGT1.1, which is generally considered the "bilirubin UGT," and
      UGT2B1, which has previously been shown to catalyze the glucuronidation of
      testosterone, chloramphenicol, and (-)-morphine. Rat UGT2B1, stably expressed in
      HK293 cells, exhibited high glucuronidation rates and catalytic efficiencies for
      many opioids, although values for (-)-morphine and nalorphine were the highest.
      In contrast, these compounds were very poor substrates for expressed rat UGT1.1.
      Comparably high glucuronidation rates and efficiencies were found for
      buprenorphine and diprenorphine with both UGT isoforms. These results suggest
      that opioids with morphinan-based chemical structures similar to (-)-morphine
      interact with UGTs differently than those with oripavine-based chemical
      structures similar to buprenorphine. To investigate the contribution of rat
      UGT1.1 and UGT2B1 in the overall rate of glucuronidation of buprenorphine in the
      rat liver, hepatic microsomes from Gunn rats (where UGT1.1 activity is absent)
      and Wistar rats (where UGT1.1 activity is present) were studied. Buprenorphine
      glucuronidation activity in Gunn rat liver microsomes exhibit approximately 25%
      of rates observed in Wistar rat liver microsomes, whereas (-)-morphine, naloxone,
      and naltrexone glucuronidation rates were not significantly different in
      microsomal preparations from Gunn and Wistar rats. These data suggest that UGT2B1
      is the major hepatic enzyme involved in the glucuronidation of (-)-morphine and
      naloxone in livers from untreated rats, whereas buprenorphine glucuronidation is
      preferentially catalyzed by rat UGT1.1.

PMID- 9029058
TI  - Major metabolic pathway for N-methyl-2-pyrrolidone in humans.
AB  - The aim was to study the metabolic pathway for N-methyl-2-pyrrolidone (NMP) in
      humans. Three healthy male volunteers were administered 100 mg NMP orally. All
      urine was collected during nine consecutive days. The identification and
      quantification of the metabolites were performed by gas chromatography/mass
      spectrometry (GC/MS). NMP, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP), N
      methylsuccinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) were found in
      urine. The mean excreted fractions for NMP, 5-HNMP, MSI, and 2-HMSI were 0.8%,
      44%, 0.4%, and 20%, respectively. There was no conjugation with glucoronic acid
      or sulfate or either 5-HNMP or 2-HMSI. One-third of the orally dosed NMP was not
      recovered in urine as either NMP, 5-HNMP, MSI, or 2-HMSI. The half-lives for 5
      HNMP, MSI, and 2-HMSI in urine were approximately 4, 8, and 17 hr, respectively.

PMID- 9029060
TI  - Frontotemporal dementia is on the MAPtau.

PMID- 9029059
TI  - Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5
      fluorouracil prodrugs.
AB  - Rats were orally co-administered sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5
      (2-bromovinyl)uracil), a new oral antiviral drug for herpes zoster, with the oral
      anticancer drug tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil) as a prodrug
      of 5-flourouracil (5-FU) once daily to investigate a toxicokinetic mechanism of
      15 Japanese patients' deaths recently caused within a brief period by the drug
      interaction of these drugs. All the rats showed extremely elevated levels of 5-FU
      in plasma and tissues, including bone marrow and small intestine, and died within
      10 days, whereas the animals given the same dose of SRV or FT alone were still
      alive over 20 days without any appreciable toxic symptom. Before their death,
      there was marked damage of bone marrow, marked atrophy of intestinal membrane
      mucosa, marked decreases in white blood cells and platelets, diarrhea with bloody
      flux, and severe anorexia as reported with the Japanese patients. Data obtained
      by in vivo and in vitro studies strongly suggested that (E)-5-(2
      bromovinyl)uracil generated from SRV by gut flora was reduced in the presense of
      NADPH to a reactive form by hepatic dihydropyrimidine dehydrogenase (DPD), a key
      enzyme determining the tissue 5-FU levels, bound covalently to DPD as a suicide
      inhibitor, and markedly retarded the catabolism of 5-FU.

PMID- 9029061
TI  - Mitochondrial function in Huntington's disease: clues for pathogenesis and
      prospects for treatment.

PMID- 9029062
TI  - Optic pathway gliomas in children with neurofibromatosis 1: consensus statement
      from the NF1 Optic Pathway Glioma Task Force.

PMID- 9029063
TI  - Hereditary frontotemporal dementia is linked to chromosome 17q21-q22: a genetic
      and clinicopathological study of three Dutch families.
AB  - Hereditary frontotemporal dementia (HFTD) is a rare autosomal dominant form of
      presenile dementia characterized by behavioral changes and reduced speech. Three
      multigeneration kindreds with this condition, in the Netherlands, were
      investigated for clinicopathological comparison and linkage analysis.
      Frontotemporal atrophy on computed tomographic scanning and/or magnetic resonance
      imaging was usually present. Single-photon emission computed tomography (SPECT)
      showed frontal hypoperfusion in the early phase of the disease. Brain tissue
      showed moderate to severe atrophy of frontal and temporal cortex with neuronal
      loss, gliosis, and spongiosis. Pick bodies were lacking in all cases of the 3
      families. The mean age of onset varied significantly between families. We report
      here evidence for linkage to chromosome 17q21-q22 with a maximum lod score of
      4.70 at theta = 0.05 with the marker D17S932. Recombination analysis positions
      the gene for HFTD in a region of approximately 5 cM between markers D17S946 and
      D17S791. Three other neurodegenerative disorders with a strong clinical and
      pathological resemblance have recently been mapped to the same chromosomal
      region, suggesting that a group of clinically related neurodegenerative disorders
      may originate from mutations in the same gene.

PMID- 9029064
TI  - Energy metabolism defects in Huntington's disease and effects of coenzyme Q10.
AB  - We investigated whether the Huntington's disease (HD) gene mutation may produce
      either primary or secondary effects on energy metabolism. 31P magnetic resonance
      spectroscopy demonstrated a significant decrease in the phosphocreatine to
      inorganic phosphate ratio in resting muscle of 8 patients as compared with 8
      control subjects. The cerebrospinal fluid lactate-pyruvate ratio was
      significantly increased in 15 patients as compared with 13 control subjects.
      Lactate concentrations assessed using 1H magnetic resonance spectroscopy are
      increased in Huntington's disease cerebral cortex. Treatment with coenzyme Q10,
      an essential cofactor of the electron transport chain, resulted in significant
      decreases in cortical lactate concentrations in 18 patients, which reversed
      following withdrawal of therapy. These findings provide evidence for a
      generalized energy defect in Huntington's disease, and suggest a possible
      therapy.

PMID- 9029065
TI  - Familial risk of migraine: a population-based study.
AB  - Estimates of familial aggregation of migraine have varied considerably due, in
      part, to methodological differences among studies. We concluded a population
      based study of 73 clinically confirmed probands with migraine, 72 matched control
      probands, and 511 of their first-degree relatives, all of whom were directly
      interviewed. The risk of migraine was 50% more likely in relatives of migraine
      probands than in relatives of controls. Migraine risk was considerably higher
      among relatives of probands with disabling migraine compared with relatives of
      probands with minimal disability. Moreover, for probands with minimal disability,
      no excess risk of migraine in female relatives was observed. Finally, in
      relatives of male migraine probands, there appears to be an excess risk of
      migraine with aura. A borderline significant relative risk of 4.04 was observed.
      No excess risk was observed among relatives of male probands who had migraine
      without aura. This study suggests that familial factors (environment related to
      the family or genetic factors) account for less than one-half of all migraine
      cases in the population. Degree of disability in the proband appears to influence
      familial risk. These results suggest that the development of migraine is
      determined by complex genetic as well as environmental factors.

PMID- 9029066
TI  - Muscle-eye-brain disease: a neuropathological study.
AB  - A combination of congenital central nervous, ocular and muscular abnormalities is
      characteristic of muscle-eye-brain disease (MEB), of Fukuyama congenital muscular
      dystrophy (FCMD), and of Walker-Warburg syndrome (WWS). The nosological
      relationship of these inherited malformative disorders is still unestablished,
      although the genetic locus for FCMD has been excluded in MEB. We present the
      first postmortem neuropathological study of MEB based on 2 male patients. Apart
      from sharply limited occipital agyric areas, their brains showed coarse gyri with
      an abnormally nodular surface ("cobblestone cortex"). Both the cerebral and
      cerebellar cortices showed a total disorganization without horizontal lamination.
      The haphazardly oriented cortical neurons formed irregular clusters or islands,
      separated by gliovascular strands extending from the pia. The ocular
      abnormalities included a pronounced glial preretinal membrane. Although MEB
      shares the cobblestone cortex-type malformation with FCMD and WWS, the cerebral
      and ocular manifestations are less severe than in WWS. Furthermore, a
      consistently weak staining for laminin alpha2 chain (merosin) was found in muscle
      biopsy specimens from 4 MEB patients, while normal immunoreactivity was observed
      for the laminin beta2 chain, reported to be severely deficient in WWS. These
      findings support nosological independence of MEB.

PMID- 9029067
TI  - Botulinum toxin treatment of muscle cramps: a clinical and neurophysiological
      study.
AB  - Botulinum toxin is now widely used in the treatment of several hyperkinetic
      movement disorders. To evaluate its efficacy in treating muscle cramping
      syndromes, we studied clinical and neurophysiological variables before and after
      botulinum toxin injections into calf muscles and small flexor muscles of the foot
      in patients with an inherited benign cramp-fasciculation syndrome. At each
      assessment the clinical severity of cramp was scored and the cramp threshold
      frequency was measured with repetitive electrical peripheral nerve stimulation.
      Botulinum toxin injection significantly lowered our patients' clinical cramp
      severity scores (mean +/- SD: before, 3.80 +/- 0.44; after, 1.40 +/- 0.54), left
      muscle strength unchanged and significantly increased their cramp threshold
      frequencies (before, 4.22 +/- 2.26 Hz; after, 10.0 +/- 3.74 Hz). The clinical
      benefit induced by botulinum toxin lasted about 3 months. Botulinum toxin
      injections also significantly reduced fasciculation potentials in relaxed muscles
      (before, 0.86 +/- 0.19 fasciculations/sec; after, 0.45 +/- 0.11
      fasciculations/sec). These findings show that local intramuscular injections of
      botulinum toxin provide effective, safe, and long-lasting relief of cramps
      possibly by reducing presynaptic cholinergic stimulation of motor nerve terminals
      and by impairing the input/output function of intrafusal and extrafusal motor end
      plates.

PMID- 9029068
TI  - Acute and chronic effects of hypoxia on the developing hippocampus.
AB  - Perinatal hypoxia is associated with both seizures arising acutely and the
      subsequent development of temporal lobe epilepsy (as determined retrospectively).
      We therefore attempted to identify acute and chronic morphological and/or
      electrophysiological hippocampal pathologies associated with experimentally
      induced hypoxia in immature rats. Pups were exposed to 15 minutes of hypoxia on 3
      successive days (starting on postnatal day 8; P8), or to 60 minutes of hypoxia on
      P10 with either one or multiple hypoxia-induced seizures. For animals
      experiencing multiple seizures, flurothyl seizure threshold was significantly
      lower than that of controls at 60 to 80 days, but not at 10 days, after hypoxia.
      Acutely, there was a treatment-related increase in the number and the density of
      pyknotic dentate and hilar neurons, in particular in animals experiencing
      multiple seizures. However, 60 to 80 days after the multiple-seizure protocol,
      the number of dentate and hilar neurons did not differ between control and
      experimental animals. Electrophysiological measures of pyramidal cell properties
      showed no striking difference between experimental and control animals at any
      time point. These results indicate that early postnatal hypoxia and hypoxia
      induced seizure episodes decrease seizure threshold in the adult but produce
      minimal acute or chronic morphological or functional changes in the hippocampus.

PMID- 9029069
TI  - Sequestration of RNA in Alzheimer's disease neurofibrillary tangles and senile
      plaques.
AB  - The polypeptide composition of neurofibrillary tangles (NFTs) and senile plaques
      (SPs) has been characterized extensively within the Alzheimer's disease (AD)
      brain. Because few data exist on the nonproteinaceous components of these
      lesions, we sought to determine if NFTs, neuropil threads (NTs), and SPs contain
      RNA species. To accomplish this, acridine orange (AO) histofluorescence was
      employed, alone or in combination with thioflavine S (TS) staining and
      immunohistochemistry to identify RNAs in paraffin-embedded tissue sections of
      hippocampus and entorhinal cortex. Postmortem brain samples came from 32 subjects
      including AD and elderly Down's syndrome (DS) patients, age-matched normal
      controls, and non-AD diseased controls. AO stained the cytoplasm of normal
      hippocampal and entorhinal neurons in all of the cases, while NFTs, NTs, and SPs
      were AO-positive in the same regions of AD and DS brains. Cytoplasmic AO
      histofluorescence was abolished with RNase, but not DNase or proteinase K,
      indicating the relative specificity of AO for RNA species. Quantitative analysis
      of double-labeled sections demonstrated that approximately 80% of TS-positive
      NFTs also were AO-positive, whereas approximately 55% of TS-stained SPs contained
      AO labeling. These novel observations demonstrate the presence of RNAs in NFTs,
      NTs, and SPs.

PMID- 9029070
TI  - Epidemiology of mutations in superoxide dismutase in amyotrophic lateral
      sclerosis.
AB  - We registered 366 families in a study of dominantly inherited amyotrophic lateral
      sclerosis. Two hundred ninety families were screened for mutations in the gene
      encoding copper-zinc cytosolic superoxide dismutase (SOD1). Mutations were
      detected in 68 families. The most common SOD1 mutation is an alanine for valine
      substitution in codon 4 (50%). We present clinical and genetic data concerning
      112 families with 395 affected individuals. The clinical characteristics of
      patients with familial amyotrophic lateral sclerosis arising from SOD1 mutations
      are similar to those lacking SOD1 defects. Mean age at onset was earlier
      (Wilcoxon test, p = 0.004) in the SOD1 group (46.9 years [standard deviation,
      12.5] vs 50.5 years [11.5] in the non-SOD1 group). Bulbar onset was associated
      with a later onset age. The presence of either of two mutations, G37R and L38V,
      predicted an earlier age at onset. Kaplan-Meier plots demonstrated shorter
      survival in the SOD1 group compared with the non-SOD1 group at early survival
      times (Wilcoxon test, p = 0.0007). The presence of one mutation, A4V, correlated
      with shorter survival. G37R, G41D, and G93C mutations predicted longer survival.
      This information suggests it will be productive to investigate other genetic
      determinants in amyotrophic lateral sclerosis and to use epidemiological
      characteristics of the disease to help discern molecular mechanisms of motor
      neuron cell death.

PMID- 9029071
TI  - Dopaminergic function in familial Parkinson's disease: a clinical and 18F-dopa
      positron emission tomography study.
AB  - There is increasing evidence for familial aggregation in Parkinson's disease
      (PD). It is possible that some asymptomatic relatives of PD patients have
      subclinical nigral Lewy body pathology and their identification could help
      determine the true prevalence of the disease. We used 18F-dopa positron emission
      tomography to investigate nigrostriatal dopaminergic terminal function in
      asymptomatic members of 7 unrelated kindreds in which at least 2 members had
      parkinsonism. Eight (25%) of the 32 asymptomatic relatives showed abnormal
      putamen 18F-dopa uptake (2.5 standard deviations below the normal mean). When
      discriminant function analysis was applied, all of these 8 subjects plus another
      3 were classified with high probability as having PD. On neurological
      examination, 5 of the 32 relatives scanned had an isolated mild postural tremor
      and 2 of these 5 had reduced putamen uptake. Our findings provide further support
      for a role of inheritance in the etiology of PD and suggest that the penetrance
      for nigrostriatal dopaminergic dysfunction in familial clusters of PD is higher
      than the prevalence of clinical parkinsonism reported in epidemiological surveys.

PMID- 9029072
TI  - Deletion and conversion in spinal muscular atrophy patients: is there a
      relationship to severity?
AB  - The spinal muscular atrophy-determining gene, survival motor neuron (SMN), is
      present in two copies, telSMN and cenSMN, which can be distinguished by base-pair
      changes in exons 7 and 8. The telSMN gene is often absent in spinal muscular
      atrophy patients, which could be due to deletion or sequence conversion (telSMN
      conversion to cenSMN giving rise to two cenSMN genes). To test for conversion
      events in spinal muscular atrophy, we amplified a 1-kb fragment that spanned
      exons 7 and 8 of SMN from 5 patients who retained telSMN exon 8 but lacked exon
      7. In all patients, sequence analysis demonstrated that cenSMN exon 7 was
      adjacent to telSMN exon 8, indicating conversion. All 5 patients with this
      mutation had type II or III spinal muscular atrophy, strongly supporting an
      association with chronic spinal muscular atrophy. We also identified 3 families
      in which 2 siblings had no detectable telSMN but presented with markedly
      different phenotypes. We suggest that sequence conversion is a common event in
      spinal muscular atrophy and is associated with the milder form of the disease.
      The severity, however, can be modified in either a positive or negative direction
      by other factors that influence splicing or expression of the sequence converted
      SMN gene.

PMID- 9029073
TI  - Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia.
AB  - Antibody-mediated autoimmunity underlies a diverse range of disorders,
      particularly in the nervous system where the extracellular domains of ion
      channels and receptors are especially vulnerable targets. We present here a novel
      means of detecting autoantibodies where the genes of the suspected target
      proteins are known, and use it to detect specific autoantibodies in acquired
      neuromyotonia (Isaacs' syndrome), a disorder characterized by hyperexcitable
      motor nerves and sometimes by central abnormalities. We expressed different human
      brain voltage-gated potassium channels in Xenopus oocytes by injecting the
      relevant alpha-subunit complementary RNA, and detected antibody binding by
      immunohistochemistry on frozen sections. Antibodies were detected to one or more
      human brain voltage-gated potassium channel in 12 of 12 neuromyotonia patients
      and none of 18 control subjects. The results establish neuromyotonia as a new
      antibody-mediated channelopathy and indicate the investigative potential of this
      molecular immunohistochemical assay.

PMID- 9029074
TI  - Involvement of the ipsilateral motor cortex in finger movements of different
      complexities.
AB  - Functional imaging and behavioral studies suggest involvement of the ipsilateral
      hemisphere in hand movements, particularly of the left hand. If this is so,
      transient disturbance of the motor cortex (M1) with repetitive transcranial
      magnetic stimulation (rTMS) may affect ipsilateral motor sequences, and the
      effects may differ on the two sides. We studied 15 right-handed subjects who
      played a simple and a complex piano sequence for 8 seconds each. Two seconds
      after the beginning of each sequence, rTMS was delivered to the ipsilateral or
      contralateral M1, or directed away from the head (control trial). Ipsilateral M1
      stimulation on either side induced timing errors in both sequences, and with the
      complex sequence induced more timing errors in the left hand than in the right
      hand. Errors of the right hand with both sequences occurred in the stimulation
      period only, but errors of the left hand with the complex sequence occurred in
      both the stimulation and poststimulation periods. We conclude that the
      ipsilateral M1 is involved in fine finger movements. The left hemisphere plays a
      greater role in timing ipsilateral complex sequences than the right hemisphere
      and may be more involved in the processing of complex motor programs.

PMID- 9029075
TI  - Motion direction discrimination in blind hemifields.
AB  - We tested motion direction discrimination with random dot cinematograms (RDCs)
      projected into the contralateral homonymous visual field defects of 10 patients
      with unilateral cerebral hemispheric lesions. Five patients had medial occipital
      lesions that spared the putative motion area in lateral occipitotemporal cortex
      and the optic radiations and other white matter tracts proximal to this site. The
      other 5 had lesions involving this area or the proximal optic radiations. Eye
      position was monitored to ensure fixation. No patient in either group
      discriminated motion direction in signal/noise RDCs at a level better than
      chance, and the performance of those with lesions restricted to medial occipital
      lobe did not differ from those with lateral occipital or optic radiation lesions.
      A subgroup of patients with medial occipital lesions also performed a "frequency
      of discrimination" experiment, using 100% coherent dot motion with stimulus
      velocities ranging as high as 79.4 degrees/sec. Their results on these tests were
      also no better than chance. Sparing of the putative motion area in lateral
      occipitotemporal cortex and its input fibers is not a sufficient condition for
      residual direction discrimination (blindsight) with RDCs in homonymous visual
      field defects.

PMID- 9029076
TI  - Maternal inheritance in Parkinson's disease.
AB  - To evaluate possible matrilineal factors in the inheritance of Parkinson's
      disease, we prospectively identified families in which a parent and multiple
      siblings had Parkinson's disease. In each of the 5 families identified, the
      affected parent was the mother (p < 0.03). The age at onset in the offspring
      generation in these 5 families was younger than the age at onset in the parental
      generation (p < 0.001). In addition, the age at onset in all patients with an
      affected mother (n = 18) was younger than the age at onset in the affected
      mothers (p < 0.001). No difference was found between the age at onset in patients
      with an affected father (n = 14) and the age at onset in the affected fathers.
      These results are consistent with a role for inherited abnormalities of
      mitochondrial DNA in the pathogenesis of at least some cases of Parkinson's
      disease.

PMID- 9029077
TI  - Molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome.
AB  - Cytochrome c oxidase deficiency is the most common biochemical defect associated
      with Leigh's syndrome. The genetic defect responsible for this deficiency has not
      been identified in any patient with Leigh's syndrome. Given that this disorder
      appears to be inherited as an autosomal recessive trait, this would suggest prima
      facie that one of the nuclear DNA-encoded cytochrome c oxidase subunits is
      affected. We report the first detailed sequence analysis of all 10 cytochrome c
      oxidase nuclear complementary DNAs and the cytochrome c oxidase mitochondrial
      genes in a Leigh's syndrome patient with cytochrome c oxidase deficiency. No
      pathological mutations were identified in any of the cytochrome c oxidase
      structural genes.

PMID- 9029078
TI  - Plasma levels of amyloid beta proteins Abeta1-40 and Abeta1-42(43) are elevated
      in Down's syndrome.
AB  - To investigate the effect of the overexpression of beta-amyloid precursor protein
      (APP) on the production of two major amyloid beta protein (Abeta) species,
      Abeta40 and Abeta42(43), we measured amounts of Abeta1-40 and Abeta1-42(43) in
      the plasma from 44 patients with Down's syndrome (DS) (age, 19-61 years) and 66
      age-matched normal controls using enzyme-linked immunosorbent assays. Plasma
      concentrations of both Abeta1-40 and Abeta1-42(43) were increased about 3-fold
      and 2-fold, respectively, in DS patients compared with normal controls.
      Especially, the increases in plasma Abeta1-40 in DS patients were statistically
      higher than the 1.5-fold increase one might predict based on the gene dose of APP
      in DS. These findings showed that both Abeta1-40 and Abeta1-42(43) are increased
      in plasma in DS patients, the former more than the latter, suggesting that
      overexpression of APP and/or other genes may have different effects on the
      production of these two Abeta species in DS.

PMID- 9029079
TI  - Pupil-involving third-nerve palsy and carotid stenosis: rapid recovery following
      endarterectomy.
AB  - We report a patient who presented with a painful pupil-involving third-nerve
      palsy. Cerebral angiography revealed a high-grade stenosis of the ipsilateral
      internal carotid artery with a 4-cm intraluminal thrombus. Following emergent
      carotid endarterectomy, the patient's partial third-nerve palsy resolved in 1
      hour. A pupil-involving third-nerve palsy may be an unusual presentation of
      impending carotid occlusion.

PMID- 9029080
TI  - Genetic evidence for the involvement of tau in progressive supranuclear palsy.
AB  - A dinucleotide repeat polymorphism in a tau intron was identified and used in a
      case-control study to analyze the genetic association of tau with several
      neurodegenerative diseases with tau pathology. Subjects with the homozygous tau
      AO alleles were excessively represented in the progressive supranuclear palsy
      (PSP) group, compared with the age-matched healthy control group. Consequently,
      this allele is more frequently found in PSP than in a group of healthy subjects.
      This trend was not found in Alzheimer's disease or parkinsonism-dementia complex
      of Guam, both of which are accompanied by major tau pathology. The result
      suggests a possible involvement of tau in the pathogenesis of PSP.

PMID- 9029081
TI  - Selegiline and mortality in Parkinson's disease: another view.

PMID- 9029082
TI  - Financial influences on career choices in neurology.

PMID- 9029083
TI  - Cutting edge: CD4+ T cells kill CD8+ T cells via Fas/Fas ligand-mediated
      apoptosis.
AB  - To explore the possibility that CD4+ T cells, described to mediate the
      elimination of themselves or B lymphocytes, could also mediate the elimination of
      CD8+ T cells, we analyzed apoptotic phenomena in cocultures of CD4+ and CD8+
      autologous T cell lines. The data show that CD8+ T cells were lysed by activated
      CD4+ helper T cells by a Fas/FasL-mediated mechanism. CD4+ T cells were not lysed
      by activated CD8+ T cells, although Fas and FasL were equally expressed and anti
      Fas Abs induced apoptosis in both CD4+ and CD8+ T cell populations. The results
      allowed us to speculate that CD4+ T cells not only help CD8+ T lymphocytes to
      mature into effector killer cells and to sustain this function but can also limit
      their growth.

PMID- 9029084
TI  - MHC affinity, peptide liberation, T cell repertoire, and immunodominance all
      contribute to the paucity of MHC class I-restricted peptides recognized by
      antiviral CTL.
AB  - MHC class I-restricted T cell responses to viral proteins focus on a limited set
      of peptides. To better understand this phenomenon, we examined all of the 26
      nonameric peptides encoded by the influenza virus A/Puerto Rico/8/34 (PR8)
      conforming to the canonical Kd binding motif. Ten peptides bound strongly to Kd
      as assessed by a cell surface stabilization assay. Five of these 10 induced in
      vitro secondary CD8+ T cell responses from splenocytes derived from PR8-immunized
      mice. The strongest responses were induced by the two previously defined
      antigenic peptides, which ranked only second and fifth in relative binding
      affinity. To examine the limiting factors in the immunogenicity of Kd-binding
      peptides, we produced recombinant vaccinia viruses (rVVs) expressing cytosolic or
      endoplasmic reticulum (ER)-targeted peptides. rVVs expressing ER-targeted
      versions of the 7 peptides with the highest relative affinities for Kd rescued Kd
      cell surface expression in T2 cells, while those expressing the 3 lowest affinity
      peptides did not. The immunogenicity of several, but not all, of the highest
      affinity peptides was greatly enhanced when expressed as VV-encoded cytosolic or
      ER-targeted peptides as compared with full length proteins. We conclude that
      limitations in the immunogenicity of class I binding peptides reflects, in order
      of decreasing importance, peptide liberation by cellular proteases, T cell
      repertoire, and TAP-mediated peptide transport. We also observed an additional
      important contributing factor: suppression of T cell responses to nondominant
      peptides by an immunodominant peptide located in the same protein.

PMID- 9029085
TI  - IL-2 signaling controls actin organization through Rho-like protein family,
      phosphatidylinositol 3-kinase, and protein kinase C-zeta.
AB  - IL-2 and IL-4 induce proliferation of TS1 alpha beta cells. Activation of the
      zeta isoform of protein kinase C is an important step in IL-2-, but not IL-4
      mediated proliferation. In addition, protein kinase C-zeta is implicated in IL-2
      mediated actin organization. Given the established involvement of the Rho family
      of small guanine nucleotide-binding proteins in organization of actin structures,
      we analyze the possible relationships between Rho and protein kinase C-zeta.
      Using the Rho-like protein family-specific toxin B from Clostridium difficile, we
      report in this work that IL-2, but not IL-4, induces a Rho-dependent activation
      of protein kinase C-zeta. This signaling event is mediated by the activation of
      phosphatidylinositol 3-kinase. In contrast, IL-4 induces a Rho-independent,
      phosphatidylinositol 3-kinase-mediated activation of protein kinase C-zeta, but
      this pathway has no implications in cytoskeleton organization.

PMID- 9029086
TI  - Early endosomes and a late endocytic compartment generate different peptide-class
      II MHC complexes via distinct processing mechanisms.
AB  - Class II MHC Ag-processing compartments and mechanisms were compared for four
      antigenic epitopes from hen egg lysozyme (HEL) and RNase. T cell assays on
      subcellular fractions of Ag-pulsed macrophages detected the initial appearance of
      HEL-(48-61):I-Ak, HEL-(34-45):I-Ak, and RNase-(90-105):I-Ek complexes in a high
      density late endocytic compartment. In contrast, RNase-(42-56):I-Ak complexes
      never appeared in high density compartments, but were rapidly generated in low
      density endosomes. This early endosomal processing mechanism was 1) chloroquine
      inhibitable; 2) less sensitive than the late endocytic mechanism to 20 degrees C
      inhibition; 3) partially resistant to depletion of nascent class II MHC molecules
      with brefeldin A, suggesting some use of recycled class II MHC molecules, whereas
      the late endocytic processing mechanism was blocked by brefeldin A; and 4)
      involved in the processing of a DM-independent complex (RNase-(42-56):I-Ak).
      Thus, distinct processing compartments and mechanisms are identified for
      different epitopes even within a single Ag.

PMID- 9029087
TI  - Lymphotactin is produced by NK cells and attracts both NK cells and T cells in
      vivo.
AB  - Injection of lymphotactin (Lptn) into the peritoneum caused an influx of
      lymphocytes at 24 h. Phenotypic analysis of the cellular influx showed that a
      large proportion of these cells were T lymphocytes; however, a large number of NK
      cells was also present. This effect of murine Lptn (mLptn) was specific since the
      cellular influx was blocked with a mLptn-specific mAb. Similar results were
      observed when Lptn was injected s.c. and the tissue was analyzed by
      immunohistochemistry using an anti-CD3epsilon mAb. Microchemotaxis assays
      confirmed that murine NK cells respond to mLptn, and also showed human NK clones
      to be similarly responsive to recombinant human Lptn (rhLptn).
      Immunohistochemical analysis of IL-2-activated murine NK cells and Northern
      analysis of human NK clones revealed that these cells also produce Lptn,
      suggesting that a self-regulatory migration mechanism exists in NK cells.
      Together these data confirm, in vivo, the lymphocyte specificity of Lptn
      previously observed in vitro and extend its chemotactic effects to the NK cell
      lineage. We also investigated the functional consequences of truncating the
      carboxyl terminus of hLptn. This truncated molecule (which is missing the
      carboxyl-terminal 22 amino acids of hLptn) had no detectable activity on human
      PBLs. In addition, while hLptn was found to attract murine splenocytes in vitro,
      the carboxyl-terminal truncated hLptn was again inactive on murine splenocytes.
      This observation indicates the presence of structural features in the carboxyl
      terminus of Lptn that are necessary for its biologic activity.

PMID- 9029088
TI  - IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of
      Th1 but not Th2 cells and exerts its effect independently of IL-12.
AB  - We have previously reported the cloning of a novel cytokine, IFN-gamma-inducing
      factor (IGIF), which shared some biologic activities with IL-12. In this study,
      we analyzed the effects of murine IGIF on the activation of T cells, and compared
      the effects with those of IL-12. IGIF alone had no effect on the activation of T
      cell lines or Th1 clones, while IGIF increased the IFN-gamma production by
      antigen-stimulated T cell lines, but had no effect on IL-4 or IL-10 production.
      As reported with IL-12, IGIF served as a costimulatory factor for Th1 clones
      stimulated with Ag on B cell APC, immobilized anti-CD3, Con A, or IL-2 to augment
      IFN-gamma production and to induce IL-2R alpha-chain expression and proliferation
      of the Th1 clones, whereas IGIF had little or no effect on the IL-4 production
      and proliferation of Th2 clones stimulated with anti-CD3 or Ag. However, IGIF
      synergized with IL-12 to further augment the IFN-gamma production of the Th1
      clones. Even in the presence of saturated amounts of IL-12, IGIF still augmented
      the IFN-gamma production and proliferation and enhanced the IL-2R alpha-chain
      expression of the Th1 clones. In contrast with IL-12, IGIF induced IL-2
      production by Ag- or anti-CD3-stimulated Th1 clones. These two findings indicate
      that IGIF and IL-12 are utilizing different signal transduction pathways. We also
      found that IGIF as well as IL-12 was endogenously released through interaction
      between Th1 cells and spleen cell APC in the presence of specific Ag, and that it
      regulated IFN-gamma production. These results further suggest that IGIF may act
      as an immunoregulatory factor in the immune response.

PMID- 9029089
TI  - Regulation of CD28 costimulation in human CD8+ T cells.
AB  - Optimal stimulation and prevention of anergy in T cells requires signaling
      through the CD28 molecule. During HIV disease progression, CD28 expression is
      lost, particularly on CD8+ T cells. Because alterations in cytokine production
      patterns occur during HIV infection, we determined whether CD8+ T cell phenotype
      or function was affected by cytokine environment. Treatment of CD8+ T cells with
      IL-4 decreased levels of both CD28 surface expression and message and increased
      CD8 expression. Furthermore, CD8+ T cells that had down-regulated CD28 had
      reduced proliferative capacity. The inhibitory effects of CD28 reduction could be
      compensated either by increased anti-CD3 or by exogenous IL-2, suggesting that
      the strength of T cell signaling necessary for the production of IL-2 and
      subsequent proliferation is negatively regulated by IL-4. CD8+ subpopulations
      with differential CD28 expression produced different patterns of cytokines,
      particularly IL-2 and IFN-gamma. Furthermore, CD8+ T cells that had reduced CD28
      levels but made their own IL-2 were able to proliferate in response to TCR
      stimulation. These results suggest that loss of CD28 expression and CD8 T cell
      function can be regulated by the cytokine environment, which may be altered
      during HIV disease progression. Whether the dysfunction of CD8+ T cells in HIV
      infection occurs by such a mechanism is the subject of future investigation.

PMID- 9029090
TI  - The mechanism of in vitro T helper cell type 1 to T helper cell type 2 switching
      in highly polarized Leishmania major-specific T cell populations.
AB  - We have previously demonstrated that highly polarized CD4+ Th1 cells isolated
      from Leishmania major-infected mice could be switched to a Th2-like phenotype
      when cultured for 1 wk in the presence of APC, L. major Ag, and IL-4, suggesting
      that the reversion of a differentiated Th response could occur at the population
      level. To investigate the cellular basis for this population switch, CD4+ lymph
      node cells from Th1-polarized L. major-infected mice were separated into two
      subsets based on the level of expression of L-selectin (Mel-14), and each subset
      was stimulated with APC and IL-2 for 1 wk in the presence or the absence of IL-4.
      Mel-14low T cells contained all of the initial Th1 activity and retained their
      Th1 phenotype when cultured with IL-4. In contrast, Mel-14high T cells did not
      produce cytokines upon challenge with L. major Ag, but gave rise to a Th2-like
      population after culture with IL-4. Thus, the newly induced Th2 population was
      derived from undifferentiated cells distinct from the Th1 cells present in the
      starting population. This undifferentiated Th precursors could be induced to
      develop into either Th1 or Th2 cells and were not recent thymic emigrants as they
      were present in mice thymectomized before infection. These experiments show that
      a chronically stimulated and highly polarized Th1 population consisted of both
      precursor T cells able to differentiate into Th2 cells and cells fully
      differentiated into Th1 cells that could not be induced to switch their pattern
      of cytokine production.

PMID- 9029091
TI  - Surface expression of hemopoietic cell phosphatase fails to complement CD45
      deficiency and inhibits TCR-mediated signal transduction in a Jurkat T cell
      clone.
AB  - Previous studies have shown that the protein tyrosine phosphatase CD45 is
      required for initiation of signal transduction through several lymphoid
      receptors. In contrast, there is increasing evidence that another protein
      tyrosine phosphatase, hemopoietic cell phosphatase (known as HCP, SHP, PTP1C,
      SHPTP-1, or PTPN6), is a negative regulator of signaling in hemopoietic cells. To
      determine the effect of HCP on signal transduction through the TCR, HCP was
      expressed as a chimeric molecule with extracellular and transmembrane domains of
      the HLA-A2 molecule (A2/HCP) on wild-type Jurkat T cells and the CD45-deficient
      variant, J45.01. In this report, we show that expression of A2/HCP, unlike A2
      chimeras containing the enzymatic regions of CD45, fails to rescue TCR-mediated
      signal transduction in J45.01. Furthermore, expression of A2/HCP on wild-type
      Jurkat T cells results in diminished inositol phosphate production following TCR
      ligation as well as markedly diminished nuclear factor of activated T cells
      promoter activity. Surprisingly, however, TCR-mediated tyrosine phosphorylation
      of phospholipase C gamma 1 remains intact in the Jurkat cells expressing the
      A2/HCP chimera. These experiments provide further evidence that HCP can serve a
      negative regulatory role in receptor-mediated signaling in immune cells.
      Additionally, our studies suggest that surface expression of HCP in T cells may
      provide a means to identify phosphotyrosine-containing proteins that are required
      for coupling signaling pathways initiated by ligation of the T cell Ag receptor.

PMID- 9029092
TI  - Type 2 helper T cell-type cytokines and the development of "infectious" tolerance
      in rat cardiac allograft recipients.
AB  - CD4-targeted therapy with a nondepleting RIB-5/2 mAb abrogates accelerated (< 36
      h) rejection in presensitized LEW rats and results in permanent acceptance of
      LBNF1 cardiac allografts in conjunction with the features of infectious
      tolerance. This study examined the role and functional significance of the Th1
      and Th2 cytokine network and systemic host allospecific Ab (allo-Ab) responses in
      the development of the infectious tolerance pathway in this model. Long term
      survival of cardiac transplants in rats treated with the tolerizing RIB-5/2 mAb
      regimen was accompanied by profound depression of Th1 (IL-2 and IFN-gamma) and
      Th2 (IL-4, IL-10) cytokines at the graft site, as shown by competitive template
      reverse transcription-PCR and immunohistochemistry. In contrast, the expression
      of Th2-type cytokines was selectively up-regulated after transfer of infectious
      tolerance by spleen cells into new generations of primary and secondary test
      recipients. Donor-specific circulating IgM allo-Ab responses were diminished
      throughout, and the switch from IgM to IgG allo-Ab was completely prevented in
      tolerant hosts, as shown by flow cytometry. The demonstration that treatment with
      cytolytic anti-CD4, but not anti-CD8, mAb recreated rejection of test cardiac
      allografts with simultaneous down-regulation of IL-4 mRNA/protein expression
      underlines the importance of this cytokine in the development of infectious
      tolerance. Hence, this report documents distinct cytokine elaboration patterns in
      animals tolerized by CD4-targeted therapy compared with those rendered tolerant
      by putative regulatory Th2-like cells. The mechanism of tolerance in anti-CD4 mAb
      treated hosts appears distinct from that operating in the absence of mAb, when
      the tolerant state is being transferred in an infectious manner to new cohorts of
      test recipients.

PMID- 9029093
TI  - A major role for matrix metalloproteinases in T cell injury in the gut.
AB  - Activated lamina propria T cells responding to luminal Ags are thought to be
      important in celiac disease and Crohn's disease, and T cells responding to
      foreign MHC products are also important in intestinal graft-vs-host disease and
      intestinal transplant rejection. However, the mechanism(s) by which T cells
      mediate damage in the gut is not known. We have previously shown that activation
      of lamina propria T cells by PWM in explant cultures of second trimester human
      small intestine produces severe tissue injury, with epithelial cell shedding and
      loss of villi. In this study, we have investigated the role of matrix
      metalloproteinases in this system. Organ culture supernatants of explants
      stimulated with PWM showed a 3-fold increase in the concentration of interstitial
      collagenase and a 10-fold increase in stromelysin-1 compared with control explant
      culture supernatants. Tissue inhibitors of metalloproteinase-1 and -2
      concentrations were unchanged. Increased metalloproteinase enzymatic activity was
      detected by gelatin and casein zymography. Western blotting revealed the active
      forms of interstitial collagenase and stromelysin-1 in PWM-stimulated culture
      supernatants. Up-regulation of mRNA for interstitial collagenase, stromelysin-1,
      and gelatinase-B was also seen. Nanomolar amounts of recombinant stromelysin-1
      added directly to explants produced rapid severe tissue injury. PWM-induced
      mucosal injury was inhibited by a synthetic peptidomimetic inhibitor of matrix
      metalloproteinases. Mesenchymal cells isolated from the mucosa of human fetal
      small intestine produced increased amounts of interstitial collagenase,
      gelatinase A, and stromelysin-1 when stimulated with IL-1beta or TNF-alpha. These
      results suggest that T cell activation in the lamina propria results in increased
      production of matrix metalloproteinases, which by degrading the lamina propria
      matrix represent a major pathway by which T cells cause injury in the gut.

PMID- 9029094
TI  - TGF-beta 1 promotes in vitro generation of dendritic cells by protecting
      progenitor cells from apoptosis.
AB  - Our previous studies demonstrated that TGF-beta 1 is required for efficient in
      vitro generation of dendritic cells (DC) from CD34+ progenitor cells under serum
      free conditions. Here we show that TGF-beta 1 promotes the growth and
      differentiation of DC primarily by protecting the viability of DC precursors and
      not by enhancing their proliferative response. Addition of TGF-beta 1 to TNF
      alpha, granulocyte-macrophage CSF, and stem cell factor-supplemented cultures had
      no significant effect on the proportions of cycling cells. Already at 72 h of
      culture, however, the proportion of apoptotic cells was reduced by more than 60%
      in the presence of TGF-beta 1. This early protective effect of TGF-beta 1
      correlates with the outgrowth of higher numbers and proportions of CD1a+ DC at
      day 7 of culture. It also correlates with a significantly reduced Fas/APO-1
      expression on TGF-beta 1 cultured cells. In contrast, granulomonocytic cells,
      also arising under these culture conditions, are not affected to such an extent.
      They are found at equal proportions, both in the presence and absence of TGF-beta
      1. The striking DC growth-promoting effect of TGF-beta 1 could only be observed
      when both TGF-beta 1 and TNF-alpha were present in the cultures. TGF-beta 1, in
      the absence of TNF-alpha, rather inhibited than enhanced cell expansion. Thus,
      for optimal in vitro DC development to occur, all four cytokines must obviously
      act in concert and the combination of TGF-beta 1 with TNF-alpha seems to be
      particularly critical.

PMID- 9029095
TI  - Development of B cells in aged mice: decline in the ability of pro-B cells to
      respond to IL-7 but not to other growth factors.
AB  - The process of B lymphopoiesis changes with increasing age, resulting in a severe
      drop in the number of pre-B cells in old mice. We have shown that the ability of
      freshly isolated pro-B cells to proliferate on stromal cells declines with age.
      In this study, we wanted to determine the reason for the diminished response of
      the aged pro-B cells. The functional alterations could arise from changes
      intrinsic to the pro-B cells or to composition of the precursor population.
      Changes in the composition of pro-B cells in marrow or long-term bone marrow
      culture system for B lymphocytes (LTBMC-B) could not account for the functional
      losses. We then examined the hypothesis that the diminished amount of
      proliferation on stromal cells was due to changes in the responsiveness to stroma
      derived cytokines. The proliferation to IL-7 but not to stem cell factor (SCF) or
      insulin-like growth factor 1 (IGF-1) was severely impaired by 24 mo of age,
      independently of the concentration of IL-7 and length of culture time. The
      reduced IL-7 response could not be explained by an increase in the percentage of
      cells undergoing apoptosis; rather, a greater frequency of aged cells remained in
      G0/G1 after IL-7 stimulation. Furthermore, the impaired responsiveness of the
      aged pro-B cells is not due to diminished expression of the IL-7R alpha-chain or
      the common gamma-chain. Since only IL-7 responsiveness is impaired, we believe
      that the underlying molecular mechanism for the cellular alterations is specific
      to signaling through the IL-7 receptor complex.

PMID- 9029096
TI  - Function of lymphocyte homing-associated adhesion molecules on human natural
      killer and lymphokine-activated killer cells.
AB  - We have analyzed the ability of fresh and rIL-2-activated human NK cells to
      interact with high endothelial venules (HEV) that are known to support
      physiologic lymphocyte extravasation, and examined the role of different adhesion
      molecules in this process. In in vitro HEV-binding assays, NK cells bound to both
      peripheral lymph node (pLN) and mucosal HEV. Activation by rIL-2 slightly
      decreased adherence to pLN HEV, but increased adherence to mucosal high
      endothelium. Markedly fewer NK cells than PBL expressed L-selectin, and the
      expression was diminished further upon treatment with rIL-2. Inhibition studies
      showed, however, that L-selectin was the most important single molecule to
      mediate adhesion to pLN HEV. Binding to mucosal HEV was mediated mainly by CD44
      and alpha 4 integrin, and the expression level of these molecules was increased
      by rIL-2, paralleling the results in HEV-binding assays. Higher m.w. forms of
      CD44, representing differentially glycosylated/variant forms of CD44, were more
      abundant on large granular lymphocytes than on unseparated PBL. We conclude that,
      despite weak recirculatory capacity, NK cells or a subpopulation of NK cells with
      the correct adhesion molecules can interact with and bind to high endothelial
      cells. Lymphokines can modulate the expression of adhesion molecules that NK
      cells utilize for HEV binding. Our results suggest that activation of NK cells
      with IL-2 may facilitate the extravasation of lymphokine-activated killer cells,
      especially to mucosal sites, whereas homing to peripheral lymphoid tissues may be
      diminished. This should be taken into consideration when procedures for
      lymphokine-activated killer cell immunotherapy are planned.

PMID- 9029097
TI  - Integrin-mediated intracellular Ca2+ signaling in Jurkat T lymphocytes.
AB  - T lymphocytes interact with components of the extracellular matrix after
      transendothelial migration on their way to sites of inflammation. To characterize
      the molecular basis of the interaction between T lymphocytes with different
      extracellular matrix proteins, we investigated the role of intracellular Ca2+ as
      a signal mediating such interactions and identified the cell surface integrins
      involved in this process. When Jurkat T lymphocytes loaded with the calcium
      sensitive fluorescent dye fura-2 were placed on coverslips coated with human
      fibronectin, human collagen types I, IV, and VI, human tenascin, human laminin I,
      or mouse laminin I, an elevation in intracellular Ca2+ concentration was
      observed. In contrast, contact of the Jurkat T lymphocytes with vitronectin and
      thrombospondin did not induce Ca2+ signals in more cells as compared with control
      measurements in which cells were in contact with only BSA or polylysine.
      Furthermore, the percentage of Jurkat T lymphocytes responding with Ca2+ signals
      to collagen types I and IV, fibronectin, and laminin I was completely reduced to
      levels observed on BSA or polylysine when the cells were pretreated with specific
      anti-integrin Abs, suggesting a role for cell surface integrins as mediators of
      cell matrix-induced intracellular Ca2+ signaling. Similar results were obtained
      with peripheral human T lymphocytes activated by phytohemagglutinin.

PMID- 9029098
TI  - Class I-deficient hemopoietic cells and nonhemopoietic cells dominantly induce
      unresponsiveness of natural killer cells to class I-deficient bone marrow cell
      grafts.
AB  - NK cells in normal mice reject bone marrow transplants from class I-deficient
      mice. In contrast, class I-deficient mice do not reject autologous cells,
      suggesting that NK cell tolerance is acquired. We employed fetal liver
      irradiation chimeras to assess two potential mechanisms that could account for
      the tolerance of NK cells in class I-deficient mice to class I-deficient cells:
      1) a positive model, in which recognition of class I+ cells molecules by NK cells
      is necessary to induce functional NK cell maturation; and 2) a negative model, in
      which interactions of NK cells with class I-deficient cells induce tolerance. In
      class I+ chimeras reconstituted with mixtures of class I+ and class I-deficient
      fetal liver cells, the rejection of class I-deficient bone marrow cell grafts was
      significantly impaired, supporting the negative model. We further addressed
      whether nonhemopoietic cells are also able to induce NK cell tolerance. Class I-
      mice reconstituted with class I+ fetal liver cells were tolerant of class I
      deficient cells, favoring this idea. Furthermore, class I-deficient mice
      reconstituted with a mixture of class I-deficient and class I+ fetal liver cells
      were more tolerant to class I-deficient cells than were class I+ mice
      reconstituted with the same fetal liver cell mixture. These results suggest that
      maximal tolerance induction requires the presence of class I-deficient
      nonhemopoietic cells.

PMID- 9029099
TI  - A shift from negative to positive selection of autoreactive T cells by the
      reduced level of TCR signal in TCR-transgenic CD3 zeta-deficient mice.
AB  - T cell selection is thought to be determined through the interaction between TCR
      and Ag/MHC. However, the contribution of the level of TCR signal to thymic
      selection remains unclear. To address this issue, we analyzed T cell selection of
      male Ag (HY)-specific TCR transgenic (HYTg) mice crossed with CD3 zeta-deficient
      (zeta KO) mice (HYTg/zeta KO), which have impaired signaling through TCR. In male
      HYTg/zeta KO mice, the number of thymocytes was comparable to that in normal
      mice, and almost all the peripheral T cells were HY specific, although these
      positively selected cells were anergic to male Ag. From these observations, the
      decrease in TCR signaling by CD3 zeta deficiency resulted in both the avoidance
      of negative selection and the acquisition of positive selection of autoreactive T
      cells in male HYTg/zeta KO mice. There was a shift of T cell selection from
      positive to no selection of HY-specific T cells in female HYTg/zeta KO mice also.
      Collectively, these findings suggest that the level of TCR signal directly
      regulates T cell selection; furthermore, the findings have integrated the models
      of T cell selection into a concept based on the quantity of TCR signal.

PMID- 9029100
TI  - Immune restoration by fetal pig thymus grafts in T cell-depleted, thymectomized
      mice.
AB  - Donor-specific tolerance can be induced across a discordant xenogeneic barrier in
      T/NK cell-depleted, thymectomized (ATX) B10 mice by grafting of fetal pig thymic
      and liver tissue (FP THY/LIV) under the kidney capsule. We have now examined the
      phenotype and function of murine T cells that develop in FP THY/LIV grafts in
      these mice. Mouse CD4+ T cells reached normal levels in PBL by 14 wk, and were
      maintained up to 30 wk. Similar proportions of splenic CD4+ cells expressed the
      naive phenotype (CD45RBhighMEL-14+CD44low) in FP THY/LIV graft recipients and
      euthymic control mice. These CD4 cells were functional, demonstrating normal
      proliferative responses and up-regulation of CD25 and CD69 after activation by
      mitogens or alloantigens. They proliferated in response to the protein Ag KLH
      presented by host MHC following in vivo immunization. ATX B10 mice grafted with
      FP THY/LIV also cleared Pneumocystis carinii infections, whereas simultaneously
      treated ATX B10 mice not receiving FP THY were unable to do so. Discordant
      xenogeneic thymus grafting can therefore restore immune competence. Thus, in
      addition to tolerance induction, xenogeneic thymic replacement might have a
      potential role in the reconstitution of immunity in patients afflicted with
      immunodeficiencies affecting the thymus.

PMID- 9029101
TI  - Protein tyrosine kinases Syk and ZAP-70 display distinct requirements for Src
      family kinases in immune response receptor signal transduction.
AB  - Engagement of immunoreceptors in hemopoietic cells leads to activation of Src
      family tyrosine kinases as well as Syk or ZAP-70. Current models propose that Src
      family kinases are critical in immune response signal transduction through their
      role in phosphorylation of tyrosine residues within immunoreceptor tyrosine
      activation motifs (ITAMs; which recruit the SH2 domains of Syk or ZAP-70) and by
      direct phosphorylation of Syk and ZAP-70. Several lines of evidence suggest that
      Syk may not show the same dependence on activation by Src family kinases as ZAP
      70. In this report, we used COS cells transiently transfected with components of
      the Fc epsilon RI complex (Lyn, Syk, and a chimeric CD8 receptor containing the
      cytoplasmic domain of the gamma subunit of Fc epsilon RI (CD8-gamma)) to examine
      the regulation of Syk activity. Syk was activated and phosphorylated in COS cells
      cotransfected with Lyn; however, in cells expressing CD8-gamma, activation of Syk
      and phosphorylation of CD8-gamma did not require coexpression of Lyn. Additional
      experiments indicate that gamma phosphorylation is dependent on Syk kinase
      activity and is independent of endogenous COS cell kinases. In parallel
      experiments, ZAP-70 was not activated by cotransfection with CD8-gamma, nor was
      CD8-gamma phosphorylated when coexpressed with ZAP-70 alone. Taken together,
      these studies indicate that Syk can be distinguished from ZAP-70 in its ability
      to be activated by coexpression with an ITAM-containing receptor without
      coexpression of a Src family kinase, and that Syk is capable of phosphorylating
      ITAM tyrosines under certain experimental conditions.

PMID- 9029102
TI  - Polymorphism in the alpha 1 helix of the HLA-B heavy chain can have an overriding
      influence on peptide-binding specificity.
AB  - Previously, we reported overlap in the repertoires of peptides endogenously bound
      by a group of HLA-B allotypes related to HLA-B7. Extending such analysis to four
      members of the B17 family and seven members of the B15 family shows that
      allotypes that share sequence identity in the alpha 1 helix of the class I heavy
      chain possess markedly similar peptide-binding specificities. Members of the B17
      family share a preference for peptides with serine, threonine, or alanine at
      position 2 and aromatic residues at the carboxyl terminus. Strikingly, the
      presence of a segment of the B17 alpha 1 helix in B*1516 and B*1517 confers the
      B17-like peptide-binding motif. The strong influence of natural variation in the
      alpha 1 helix is exemplified by the differences in peptide-binding specificity of
      B15 allotypes related by conversion events that replaced segments of the alpha 1
      helix. In contrast, evolutionary changes that are confined to the alpha 2 domain
      confer less dramatic change. They do not perturb the primary anchors of the
      peptide-binding motif but can modulate the specificity through development and
      diversification of secondary anchors. Our results, in combination with those
      obtained previously for other HLA-B allotypes, suggest a general trend whereby
      polymorphism in the alpha 1 helix is the overriding influence on peptide-binding
      specificity of HLA-B allotypes, while amino acid substitutions in the alpha 2
      domain play a more modulatory role.

PMID- 9029103
TI  - Anti-human kappa opioid receptor antibodies: characterization of site-directed
      neutralizing antibodies specific for a peptide kappa R(33-52) derived from the
      predicted amino terminal region of the human kappa receptor.
AB  - Site-directed polyclonal Abs specific for a synthetic peptide with sequence
      homology to the predicted N-terminal sequence of the human kappa opioid receptor
      [anti-kappa R-(33-52)] are capable of binding to normal human cells and cell
      lines expressing mRNA specific for the human kappa receptor. Flow cytometric
      analysis of 1) a neuronal cell line (NT2), 2) blood-derived CD14+ monocytes, 3)
      monocyte-like cell lines (U937 and THP 1), 4) blood-derived CD3+ T cells and a T
      cell line, and 5) human B cell lines bound anti-kappa R-(33-52) in a specific
      manner. Anti-kappa R-(33-52) was also found to specifically neutralize the
      immunosuppressive activities associated with the kappa R-selective agonist
      U50,488H. This antiserum was found to block U50,488H-mediated inhibition of 1)
      Staphylococcus aureus Cowen strain I-induced B and T lymphocyte proliferation, 2)
      PHA-induced T lymphocyte proliferation, and 3) S. aureus Cowen strain I-induced
      IgG production. However, this antiserum failed to neutralize mu R-selective
      agonist (Tyr-D-Ala-Gly-NMe-Phe-Gly-ol)-mediated suppression of IgG synthesis.
      Finally, the kappa R-selective antagonist nor-binaltorphimine hydrochloride
      inhibits the binding of anti-kappa R-(33-52) to the U937 cell line. These results
      suggest that anti-kappa R-(33-52) specifically interacts with the human kappa R
      molecule. Studies conducted with anti-kappa R-(33-52) indicated that this
      antiserum effectively blocked U50,488H-mediated immunosuppression, but by itself
      did not enhance or suppress lymphocyte activation. These data suggest that anti
      kappa R-(33-52) 1) does not interact with the effector binding site of the
      receptor, but sterically interferes with U50,488H binding to the receptor; and/or
      2) the antiserum interacts with a secondary binding site that is important for
      ligand binding, but may not be involved in signal transduction.

PMID- 9029104
TI  - The 14.1 surrogate light chain promoter has lineage- and stage-restricted
      activity.
AB  - The 14.1 surrogate light chain protein is expressed on human pre-B lymphocytes in
      association with Vpre-B and the mu Ig heavy chain to form the pre-B receptor. The
      14.1 chain has also been called the lambda (lambda)-like (LL) protein and is
      homologous to murine lambda5. The 14.1(IGLL1) gene is expressed in a lineage- and
      stage-restricted manner. To understand the molecular mechanism of the 14.1 gene
      tissue- and stage-specific expression, we analyzed the 5'-flanking region and
      characterized the promoter for this gene. In this report, we identify two DNase I
      hypersensitive sites located at 2.6 kilobases (HSS 1) and 0.2 kilobases (HSS 1)
      upstream of 14.1 exon 1. These hypersensitive sites are present in pre-B
      lymphocyte cell lines, but absent in mature B and T cell lines. We have used
      RNase protection analysis to localize the 5' major transcriptional start site and
      rapid amplification of 5' cDNA ends to identify multiple start sites within the
      TATA-less, GC-rich 14.1 promoter. The region encompassing HSS 2 was analyzed for
      promoter activity. Transfection of cell lines with a series of truncated segments
      of the 5' flanking region linked to the luciferase reporter gene revealed that
      the 14.1 promoter is lineage- and stage-specific, and we localized this activity
      to positions +150 to +227 relative to the 5' major transcriptional start site.

PMID- 9029105
TI  - Molecular cloning, chromosomal localization, expression, and functional
      characterization of the mouse analogue of human CD59.
AB  - We have previously described the isolation and cloning of the rat analogue of the
      human complement inhibitor CD59 (hCD59). Using the rat CD59 (rCD59) coding region
      as probe, we have isolated positive cDNAs from a mouse kidney cDNA library.
      Sequence analysis of these clones indicated that they contained an open reading
      frame encoding a 124 amino acid protein. Comparisons with the known sequences of
      hCD59 and rCD59 suggested that the clones contained a full-length cDNA encoding
      the mouse analogue of CD59 (mCD59). The cDNA encoded a 81-bp 5'-flanking region,
      a 23 amino acid NH2-signal peptide, a 101 amino acid coding region including
      putative N-glycosylation sites and a glycosyl phosphatidylinositol (GPI)
      anchoring signal, and approximately 0.8 kb 3'-untranslated flanking region.
      Reverse transcriptase PCR revealed the presence of mCD59 mRNA in all mouse
      tissues examined. The gene for mCD59 was mapped by fluorescence in situ
      hybridization to the E2-E4 region of mouse chromosome 2, a region that includes
      areas syntenous with the location of the human CD59 gene on chromosome 11p13.
      Expression of mCD59 in a CD59-negative human cell line conferred protection
      against lysis by complement from rodent, human, and several other species,
      confirming that mCD59 was the functional analogue of hCD59 and that function was
      not species restricted. The expressed protein was glycosyl phosphatidylinositol
      anchored as demonstrated by its partial removal from U937 cells on treatment with
      phosphatidylinositol-specific phospholipase C. Abs raised against the expressed
      protein demonstrated the presence of mCD59 on all mouse blood cell types and on
      several mouse cell lines and neutralized function of mCD59 on mouse E and
      expressed on U937. Western blot analysis revealed that both expressed and
      endogenous mCD59 had a molecular mass of 22 to 24 kDa.

PMID- 9029106
TI  - Purification and characterization of the pig analogue of human membrane cofactor
      protein (CD46/MCP).
AB  - A panel of mAbs were raised against pig lymphocytes. Seven mAbs
      immunoprecipitated a 50- to 60-kDa membrane-bound protein. This protein, termed
      JM4C8-Ag, was expressed on a wide variety of cells, including all circulating
      cells and cells of fibroblast, epithelial, and endothelial origin. The JM4C8-Ag
      was transmembrane-anchored and glycosylated. One of the Abs was used in
      immunoaffinity chromatography to isolate JM4C8-Ag from erythrocyte membranes. N
      terminal amino acid analysis through the first 28 residues showed a 43% homology
      with the human complement regulatory molecule membrane cofactor protein (MCP;
      CD46). The purified protein had cofactor activity for factor I-mediated cleavage
      of human and pig C3b, confirming its identity as the pig analogue of human MCP.
      The purified protein also strongly inhibited lysis of rabbit erythrocytes by
      human and pig complement after activation of the classical or alternative
      pathway. This is the first report of a nonprimate analogue of MCP. The presence
      of a resident MCP on pig cells capable of acting as a cofactor in the control of
      human complement activation has consequences for the use of pig organs in
      xenotransplantation.

PMID- 9029107
TI  - A cyclic hexapeptide is a potent antagonist of alpha 4 integrins.
AB  - The alpha 4 integrins mediate leukocyte adhesion to specific counter-receptors,
      including vascular cell adhesion molecule-1 (VCAM-1), the fibronectin splice
      variant containing connecting segment 1 (CS1), and mucosal addressin cell
      adhesion molecule-1. A series of cyclized peptides based on the LDV sequence of
      CS1 were synthesized and assayed for inhibition of alpha 4 integrin binding. The
      most potent peptide, C*WLDVC* (where * indicates disulfide-linked residues),
      inhibited alpha 4 beta 1-dependent binding of lymphocytes to VCAM-1 and CS1 with
      half-maximal inhibition achieved at 1 to 3 microM of peptide. The peptide proved
      more potent when the lymphocytes were activated with 1 mM MnCl2; half-maximal
      inhibition was reached at 0.4 and 0.05 microM for VCAM-1 and CS1, respectively.
      This represents a 100- to 800-fold increase in potency over a linear CS1 peptide
      in these same assays. C*WLDVC* also inhibited alpha 4 beta 7-dependent lymphocyte
      binding to the ligands mucosal addressin cell adhesion molecule-1, VCAM-1 and
      CS1. Immunoprecipitation of radiolabeled integrin indicated that the peptide
      could bind alpha 4 beta 1 and alpha 4 beta 7 directly and elute alpha 4 beta 1
      from a CS1-conjugated agarose resin. The peptide showed selectivity for alpha 4
      integrins in that it effectively inhibited alpha 4 beta 1-dependent, but not
      alpha 5 beta 1-dependent, binding of cells to intact fibronectin. Due to its
      small size and potency, C*WLDVC* may serve as a useful tool for the study of
      alpha 4 integrin biology and the development of small molecule therapeutics.

PMID- 9029108
TI  - Analysis of IgM structures involved in J chain incorporation.
AB  - J chain is associated with pentameric IgM and polymeric IgA. In IgM, J chain is
      disulfide bonded to the C575 residue of the mu-chain, located in the mu tail
      piece (mu tp). Previous studies indicated that mu tp is not sufficient to mediate
      J chain incorporation into polymeric Ig. In this study, we analyzed which other C
      mu domains are involved in J chain incorporation. Three altered forms of mouse
      IgM were analyzed: IgM lacking the C mu 1 domain, IgM in which the C mu 2 and C
      mu 3 domains were replaced by the hinge region and the C gamma 2 domain of IgG2b,
      and IgM, in which the C mu 4 domain was replaced by C gamma 3. We found that
      neither C mu 1, C mu 2, nor C mu 3 was absolutely required for J chain
      incorporation. The importance of C mu 4 could not be fully analyzed because the C
      gamma 3 replacement mutant failed to form polymers. Also, we found that the
      glycosylation site at asparagine 563 of mu tp was important for J chain
      incorporation. Disruption of this site by replacement of either asparagine 563 by
      tyrosine or serine 565 by phenylalanine resulted in diminished J chain
      incorporation and increased production of hexameric IgM. These results
      demonstrate the importance of structural elements located close to mu tp in the
      incorporation of J chain into IgM.

PMID- 9029109
TI  - Regulation of class I-restricted epitope processing by local or distal flanking
      sequence.
AB  - Influenza A/Puerto Rico/8/34 nucleoprotein (NP) contains an H-2Kd-restricted CD8+
      T cell (T CD8+) epitope spanning amino acid residues 147-155. It was previously
      demonstrated that expression of NP147-155 and NP147-158 in isolation via
      "minigene"/recombinant vaccinia virus (vac) technology leads to sensitization of
      target cells for NP-specific killing while expression of 147-158 lacking the
      arginine at position 156 (termed here as 147-155TG) does not. The presentation
      block was overcome by placing this fragment into the context of full length NP.
      We show that addition of a single amino acid, Met159, to the C terminus of the
      blocked peptide (creating 147-155TGM) restores presentation. Presentation of 147
      155TGM was not due to trimming in the exocytic compartment, consistent with
      severe limitations on C-terminal trimming activity in this location. Rescued
      presentation was also achieved when the blocked construct was extended in the N
      terminal direction only, but in this case more than 55 amino acids of flanking
      sequence were required. The transition to presentation was abrupt, with 91-155TG
      and shorter constructs showing little or no detectable presentation and 90-155TG
      showing full level presentation. Presentation could not be attributed to
      acquisition of conventional targets for ubiquitination since mutation of all Lys
      residues, to which the ubiquitin moiety is conjugated, does not abrogate
      presentation. Rescued presentation was not inhibited by the peptide aldehyde N
      acetyl-L-leucinyl-L-leucinal-L-norleucinal, suggesting that the added elements
      may be recruiting nonproteasomal activity. We have therefore identified and begun
      to characterize protease targeting of regulatory elements, both local and distal
      to an epitope, which strongly influence the ability of the epitope to be excised.

PMID- 9029110
TI  - Non-killer cell-specific transcription factors silence the perforin promoter.
AB  - Perforin is a pore-forming killer protein exclusively expressed by cells
      functionally defined as cytolytic lymphocytes. Previous reporter gene
      investigations have indicated that the cell-type-specific expression of the
      perforin gene is determined by the promoter and upstream region but the
      respective cis- and trans-acting molecules remain to be identified. In this
      investigation, we differentially display DNA-protein interactions of perforin
      positive vs perforin-negative cell types and functionally test their biological
      relevance. Our results provide molecular evidence for the transcriptional
      repression of the perforin gene in non-killer cells by two novel regulatory
      elements. One of the respective transcription factors that are exclusively
      expressed by non-killer cells appears to be an Ets family member. Thus, the
      development of cells expressing perforin, and perhaps cytolytic lymphocytes in
      general, may involve a shutdown of the genes for these proteins.

PMID- 9029111
TI  - Differential responses to challenge with live and dead Mycobacterium bovis
      Bacillus Calmette-Guerin.
AB  - Bacillus Calmette-Guerin (BCG) vaccination has been shown to protect against
      challenge with virulent Mycobacterium tuberculosis in a range of experimental
      animal models: in each case, protective efficacy requires vaccination with live
      bacteria. With the goal of moving to a new generation of safer, nonliving
      vaccines, efforts have been made to identify the factors that determine the
      efficacy of live vaccination. We show that injection of live, but not dead, BCG
      induces localized swelling in the mouse footpad model. Live and dead bacteria
      induce similar responses during the first week after vaccination as determined by
      immunohistochemical analysis of the site of injection and of the draining lymph
      node. The subsequent differential response is characterized by migration of acid
      fast bacilli to the draining lymph node in the case of the live vaccine. This is
      accompanied by an increase in mononuclear cells in the lymph node and by
      expression of inducible nitric oxide synthase (iNOS) both in the lymph node and
      at the site of injection. The ability of the bacteria to migrate to the lymph
      node may be an important element in the efficacy of live BCG vaccination.

PMID- 9029112
TI  - T cell priming against vesicular stomatitis virus analyzed in situ: red pulp
      macrophages, but neither marginal metallophilic nor marginal zone macrophages,
      are required for priming CD4+ and CD8+ T cells.
AB  - Since extensive degradation may be required to present complex Ags, we addressed
      whether macrophages (M phi) might function as APC for anti-viral cell-mediated
      immune responses. To study this question, murine splenic M phi were depleted by
      i.p. administration of liposome-encapsulated dichloromethylene diphosphonate
      (Cl2MDP-liposomes or clodronate-liposomes) before priming mice with vesicular
      stomatitis virus (VSV). Cl2MDP-liposome treatment resulted in the rapid (1-day)
      depletion of splenic M phi that was associated with a suppression of the ability
      of M phi-deficient mice to generate secondary anti-VSV CTL and Th cell
      proliferative responses in vitro. Control studies demonstrated that splenic
      dendritic cells were not adversely affected by treatment with Cl2MDP-liposomes.
      To assess the contribution of splenic M phi subpopulations to T cell priming
      against this virus, priming was delayed following treatment with Cl2MDP-liposomes
      until specific M phi subsets had repopulated the spleen. This analysis revealed
      that repopulation by red pulp M phi, but not with other splenic M phi subsets,
      was associated with the ability to mount normal secondary CTL and Th cell
      responses against VSV. Depletion of splenic, but not resident, peritoneal M phi
      by i.v. injection of Cl2MDP-liposomes did not rescue T cell priming in VSV
      infected mice. Thus, only red pulp M phi, and not other splenic or peritoneal M
      phi populations, are necessary for T cell priming to VSV, a biochemically complex
      Ag.

PMID- 9029113
TI  - Activation of the lymphotoxin beta receptor by cross-linking induces chemokine
      production and growth arrest in A375 melanoma cells.
AB  - The lymphotoxin beta receptor (LT beta R) was originally described as a
      transcribed sequence encoded on human chromosome 12p, with homology to the TNF
      receptor family. Subsequently, a recombinant LT beta R was shown to bind LT alpha
      LT beta heteromeric complexes. In this study, we have shown that LT beta R is
      expressed in a variety of tissues and cell lines of monocytic lineage, as well as
      in fibroblast and human melanoma cell lines. Unlike other members of the TNF
      receptor family, LT beta R is not expressed by peripheral blood T cells. A
      chimeric fusion protein consisting of the extracellular domain of LT beta R fused
      to the Fc region of human IgG1 was used to develop mAbs against LT beta R. Cross
      linking LT beta R on A375 melanoma cells with these Abs generated an
      antiproliferative signal. In addition, the IL-8 and RANTES chemokines, early
      indicators of inflammation, were secreted by the A375 melanoma line and the
      WI38VA13 fibroblast line in response to cross-linking of LT beta R. These same
      activities could be induced by membrane-bound and soluble LT beta and LT alpha LT
      beta oligomers.

PMID- 9029114
TI  - Mechanism of complement inactivation by glycoprotein C of herpes simplex virus.
AB  - Glycoprotein C (gC) of both herpes simplex virus type 1 (HSV-1) and HSV-2
      interacts with complement C3b and protects the virus from complement-mediated
      neutralization. To study the mechanism by which gC modulates complement
      activation, we expressed both gC-1 and gC-2 in a baculovirus expression system.
      Baculovirus recombinants containing gC genes spanning the entire gC-1 sequence
      (gC-1-TMR) or only the extracellular domain(s) of gC-1, gC-2, or a deletion
      mutant of gC-1 lacking residues 33 through 123 were expressed in sf9 insect
      cells. Binding of the expressed proteins to human C3 and C3 fragments was
      assessed by direct and competition ELISA. All four expressed proteins bound to
      C3, C3b, and C3c but not to C3d, suggesting 1) that the binding sites for these
      proteins are located in the C3c region of C3; and 2) that gC, in contrast to
      other C3-binding proteins, interacts with native C3. We have also examined the
      interaction of native C3 with gC-1 expressed on the HSV-1-infected cells.
      Analogous to recombinant proteins, gC-1 expressed on the infected cells also
      bound to native C3. The ability of baculovirus-expressed gCs to inhibit the
      interaction of C3b with its ligands was also analyzed. We found that gC-1, but
      not gC-2, inhibited the binding of C5 and properdin to C3b and also inhibited the
      alternative pathway-mediated lysis of rabbit erythrocytes. Inhibition of
      alternative pathway-mediated lysis and properdin binding to C3b, but not of C5
      binding to C3b, required the transmembrane segment of the gC-1. The specificity
      of gC interactions was examined by studying the interaction of gC with C3 from
      various species. In contrast to properdin, both gCs bound to cobra C3; this
      finding suggests that gC-1 and properdin bind to different sites on C3b. Further
      analyses suggested that gC-1 sterically hindered access of C5 and properdin to
      C3b.

PMID- 9029115
TI  - Expression of lung inducible nitric oxide synthase protein does not correlate
      with nitric oxide production in vivo in a pulmonary immune response against
      Cryptococcus neoformans.
AB  - Mice infected intratracheally with Cryptococcus neoformans (Cne) require CD4 and
      CD8 T cells, IFN-gamma, and M phi production of nitric oxide (NO) for effective
      resolution of the pulmonary infection. Differences exist among strains of mice in
      clearing the infection. C.B-17 mice reduced Cne lung burden at a significantly
      greater rate than C57BL/6 (B6) mice and resistance correlated with greater IFN
      gamma production by C.B-17 lung-associated lymph node cells. We examined whether
      the differences observed in the ability of B6 vs C.B-17 mice to clear Cne was due
      to 1) numbers of inflammatory cells recruited to the lung, 2) the activation
      state of the recruited cells as measured by expression of inducible nitric oxide
      synthase (iNOS), and/or 3) the in vivo production of NO as measured by
      quantitating urine nitrates. The level of iNOS protein was identical in lungs
      from both strains of mice during Cne infection as determined by Western blot
      analysis of whole lung homogenates and immunocytochemistry of isolated lung
      macrophages. Surprisingly, in vivo studies of iNOS activity indicated that NO
      production in B6 mice was significantly less than that in C.B-17 mice. While
      single cell suspensions from lungs of either mouse strain produced identical
      amounts of NO, NO production by lung explants paralleled in vivo urinary nitrate
      excretion, suggesting that the maintenance of pulmonary architecture and cell
      cell interaction was necessary for suppression of iNOS activity in B6 mice. These
      data strongly implicate the existence of mechanisms that regulate NO production
      at the level of enzyme activity during infections and have important implications
      for analyzing the role of iNOS during an immune response in in vivo models.

PMID- 9029116
TI  - Activation of human macrophage fungistatic activity against Histoplasma
      capsulatum upon adherence to type 1 collagen matrices.
AB  - Human monocyte/macrophages (Mphi) were adhered to extracellular matrix proteins,
      and the intracellular growth of Histoplasma capsulatum (Hc) yeasts were
      quantified and compared with their growth in Mphi adhered to plastic. Freshly
      isolated monocytes and cultured monocyte/derived Mphi adhered to type 1 collagen
      gels, but not to nongelled collagen-, fibronectin-, laminin-, or vitronectin
      coated surfaces, demonstrated significant fungistatic activity against Hc yeasts.
      Activation of Mphi developed immediately upon adherence to the collagen matrices
      (1 h) and did not require additional time in culture. In addition, many of the
      yeasts were digested by 24 h postinfection. Mphi adhered to collagen maintained
      their fungistatic activity for up to 4 days, during which time monolayers
      cultured on plastic were destroyed. Culture of Mphi in the presence of IFN-gamma
      or TNF-alpha for 24 h before infection did not augment the fungistatic activity
      of collagen-adherent Mphi. Likewise, culture of monocytes on collagen gels with
      IL-3, granulocyte-Mphi CSF (GM-CSF) or Mphi CSF (M-CSF) for 7 days did not
      enhance Mphi fungistatic activity above that obtained by monocytes cultured on
      collagen alone. The mechanism(s) of Mphi-mediated fungistasis was not associated
      with production of toxic oxygen radicals, nitric oxide, or the restriction of
      intracellular iron. However, experiments with horseradish peroxidase-labeled gold
      colloids and immunoelectron microscopy demonstrated that phagolysosomal fusion,
      which is minimal in Hc-infected Mphi adhered to plastic, is enhanced
      significantly at both 1 h and 24 h postinfection in Mphi adhered to collagen
      matrices. These data suggest that in vivo, matrix-bound Mphi may express a
      previously unrecognized antifungal activity that proceeds in the absence of
      exogenous cytokines and is mediated, in part, by overcoming the capacity of Hc
      yeasts to inhibit Mphi phagolysosomal fusion.

PMID- 9029117
TI  - Protective monoclonal antibody defines a circumsporozoite-like glycoprotein
      exoantigen of Cryptosporidium parvum sporozoites and merozoites.
AB  - The apicomplexan protozoan parasite Cryptosporidium parvum causes a diarrheal
      disease in humans and other mammals for which specific therapy and
      immunoprophylaxis are unavailable. Passive immunization with Abs against whole C.
      parvum organisms has variable efficacy in immunocompromised or neonatal hosts.
      Because apical and surface-exposed zoite Ags of the Apicomplexa are critical to
      infectivity and targets of protective immunity, we examined the ability of mAbs
      generated against such Ags in C. parvum sporozoites to passively protect against
      infection and identify biologically relevant parasite molecules. A panel of mAbs
      was produced against affinity-purified native Ags using sporozoite apical- and
      surface-reactive mAb C4A1 as binding ligand. One resulting mAb, designated 3E2,
      elicited prominent morphologic changes in sporozoites and merozoites
      characterized by rapid and progressive formation, posterior movement, and release
      of membranous Ag-mAb precipitates. These changes had a striking resemblance to
      the malarial circumsporozoite precipitate (CSP) reaction. Sporozoite infectivity
      was completely neutralized after in vitro exposure to 3E2 and the CSP-like
      reaction. Furthermore, orally administered 3E2 completely prevented or markedly
      reduced infection in neonatal BALB/c mice. 3E2 bound to apical complex and
      surface molecules of zoites and was demonstrated in membranous precipitates by
      immunoelectron microscopy. In Western blots, 3E2 recognized multiple 46 to
      approximately 770 kDa sporozoite Ags and an approximately 1300-kDa Ag designated
      CSL, also expressed by merozoites. CSL was characterized as a soluble
      glycoprotein exoantigen released by infectious sporozoites. Further, CSL was
      determined to be the molecular species mechanistically involved in the CSP-like
      reaction by its identification in SDS-PAGE gels and Western blots of purified
      membranous precipitates. These findings indicate that CSL has a functional role
      in sporozoite infectivity and is a candidate molecular target for passive or
      active immunization against cryptosporidiosis.

PMID- 9029118
TI  - Identification of subdominant CTL epitopes of the GP100 melanoma-associated tumor
      antigen by primary in vitro immunization with peptide-pulsed dendritic cells.
AB  - The gp100 melanoma-associated tumor Ag was selected as a model system to study
      the diversity of human antitumor cytotoxic T cell responses. First, peptides
      corresponding to dominant gp100 HLA-A2.1-restricted CTL epitopes were tested
      using lymphocytes from normal volunteers and an in vitro priming protocol that
      uses peptide-pulsed dendritic cells as APCs and IL-7 and IL-10 as immune
      enhancing cytokines. High CTL activity toward both peptide-pulsed target cells
      and gp100+ melanoma cells was obtained with four out of five peptides tested.
      Second, HLA-A2.1-binding peptides from gp100 that do not appear to represent CTL
      epitopes in melanoma patients were also tested for their capacity to induce CTL
      using the in vitro priming protocol. Three of six peptides tested induced CTL in
      lymphocytes from normal volunteers. One of these peptides was also immunogenic
      for lymphocytes derived from a melanoma patient in remission. Because these three
      CTL epitopes were not recognized in the natural immune response in melanoma
      patients but do appear as immunogens when peptides are used to induce the T cell
      response, they may be considered as typical "subdominant" epitopes. The results
      are discussed in the context of the usefulness of this approach to detail the
      immunologic potential of a given tumor-associated Ag and its relevance for the
      design of effective immune-based therapies.

PMID- 9029119
TI  - Aggregation of low affinity IgG receptors induces mast cell adherence to
      fibronectin: requirement for the common FcR gamma-chain.
AB  - Mast cells have been reported to increase at sites of immune complex-induced
      inflammation where these cells appear to potentiate the inflammatory response.
      The mechanism by which mast cells accumulate at these sites is unknown. One
      possibility is that aggregation of low affinity IgG receptors could signal mast
      cells to adhere to components of the connective tissue matrix. To test this
      hypothesis, we first added aggregated IgG to a mast cell adhesion assay employing
      fibronectin as a matrix component and observed an increase in cell adhesion. Even
      a small amount of aggregated IgG (< 60 ng/ml) demonstrated by fast protein liquid
      chromatography in untreated IgG preparations was sufficient to increase mast cell
      adhesion by 100%. We next explored the Fc gamma receptors involved. Fc
      gammaRII/III, which are receptors for oligomeric IgG and were first verified as
      present on these mast cells by FACS analysis and immunoprecipitation, signaled
      mast cells to rapidly adhere to fibronectin when aggregated with the anti
      receptor Ab2.4G2. The adhesion process mediated by Fc gammaRII/III was not
      associated with beta-hexosaminidase release. Bone marrow-cultured mast cells from
      common gamma-chain deficient mice, unlike mast cells cultured from +/+ mice, did
      not respond to Fc gammaRII/III aggregation. This demonstrated requirement for a
      gamma-chain implicates oligomeric Fc gammaRIII in the adhesion process. Thus,
      aggregation of Fc gammaRIII on mast cells leads to mast cell adhesion,
      demonstrating a previously unknown biological function for this receptor on mast
      cells and providing a mechanism for mast cell accumulation in immune complex
      dependent inflammation.

PMID- 9029120
TI  - Phosphatidyl serine is involved in the reduced rate of transcription of the
      inducible nitric oxide synthase gene in macrophages from tumor-bearing mice.
AB  - Upon stimulation with LPS, peritoneal-elicited macrophages (PEM) from mammary
      tumor-bearing mice display a diminished ability to produce nitric oxide (NO) and
      lyse tumor targets. In contrast, when these cells are stimulated with LPS in
      combination with IFN-gamma, they perform these functions at normal levels.
      Kinetic studies revealed that these defects became more pronounced with tumor
      progression and were accompanied by similar changes in inducible nitric oxide
      synthase (iNOS) mRNA levels. Since this tumor is known to produce PGE2,
      granulocyte-macrophage CSF (GM-CSF), and phosphatidyl serine, we evaluated the
      effects of these products on NO production and cytolytic activity. Pretreatment
      of normal PEM with PGE2 or recombinant GM-CSF had negligible effects on NO
      production and cytolytic capacity. In contrast, phosphatidyl serine caused a
      concentration-dependent inhibition of these functions in response to LPS, which
      could be partially overcome by the addition of IFN-gamma. Moreover, iNOS mRNA
      levels paralleled these changes and were analogous to the alterations observed in
      the tumor-bearers' PEM. iNOS mRNA stability was not reduced in these cells;
      however, the rate of transcription was diminished relative to normal levels,
      suggesting that the defects causing these alterations are occurring at or before
      the level of iNOS transcription. These data implicate tumor-derived phosphatidyl
      serine in the alterations observed in tumor-bearers' macrophages and suggest that
      reduced iNOS transcription is responsible for the diminished capacity of these
      macrophages to produce NO and lyse tumor targets.

PMID- 9029121
TI  - Response to local inflammation of IL-1 beta-converting enzyme- deficient mice.
AB  - IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to the mature, released
      form. Although other proteases can process pro-IL-1 beta, ICE-deficient (ICE -/-)
      mice do not release mature IL-1 beta in response to endotoxin. The purpose of our
      study was to investigate the response of ICE -/- mice in two models of local
      inflammation, turpentine-induced tissue damage and zymosan-induced peritonitis.
      No differences were observed in the development of the systemic acute phase
      response after turpentine administration between wild-type and ICE -/- mice, but
      this response was completely impaired in IL-1 beta -/- mice. Accordingly, the
      levels of mature IL-1 beta produced in response to turpentine did not differ
      between wild-type and ICE -/- mice. In contrast, following zymosan-induced
      peritonitis, the levels of mature IL-1 beta were significantly lower in ICE -/-
      mice. This was associated with a 50% decrease in cellular infiltrate in ICE -/-
      mice compared with that in wild-type controls. The reduced production of zymosan
      induced mature IL-1 beta in ICE -/- mice was also observed from cultured
      peritoneal or spleen cells. Our results demonstrate that in turpentine-induced
      tissue necrosis, precursor IL-1 beta is processed by non-ICE proteases, but in
      complement-mediated inflammation, ICE participates in the processing of the IL-1
      beta precursor.

PMID- 9029122
TI  - Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse.
AB  - The dual radiolabeled mAb technique was used to quantify the constitutive and
      induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular
      cell adhesion molecule-1 (VCAM-1) in the microvasculature of different organs of
      the mouse. The constitutive expression of both adhesion molecules varied
      significantly between tissues, with ICAM-1 levels consistently higher than VCAM-1
      in all tissues studied. Following systemic administration of endotoxin (LPS), an
      increased surface expression of both adhesion molecules occurred in most organs,
      with the largest increases for ICAM-1 (2 to 3x increase) noted in the heart,
      small intestine, and brain, while heart and small intestine exhibited the largest
      increases in LPS-induced VCAM-1 expression (2 to 5x increase). These responses
      occurred in the face of an unaltered expression of platelet endothelial cell
      adhesion molecule-1 (PECAM-1) in all tissues. TNF-alpha also elicited an
      increased expression of both adhesion molecules, with initial increases noted at
      2 to 5 h, peak levels at 5 to 9 h, and a sustained elevation above baseline at 24
      h. The TNF-alpha-induced increases in both ICAM-1 and VCAM-1 were dose dependent,
      with significant up-regulation noted at 5 microg/kg and maximal increases
      occurring at 10 to 25 microg/kg. These studies indicate that while there are
      significant quantitative differences in constitutive and induced expression of
      murine ICAM-1 and VCAM-1, the kinetics and dose-response characteristics of the
      two adhesion molecules to TNF-alpha are qualitatively similar.

PMID- 9029123
TI  - A novel CD8 molecule expressed by alveolar and peritoneal macrophages stimulates
      nitric oxide production.
AB  - Macrophages play an essential role in host defense, and we have identified a
      novel CD8 molecule, on alveolar and peritoneal macrophages, that may be involved
      in regulating this function. Flow cytometric analysis of bronchoalveolar lavage
      from normal rats identified a large number of CD8-positive cells that could not
      be accounted for by T lymphocytes. Within the scatter profile region in which the
      majority of cells were alveolar macrophages (OX41; 89 +/- 1%), 63 +/- 5% of the
      cells stained positively for CD8alpha (OX8) and 52 +/- 3% for CD8beta (341).
      Double-staining of lavage cells confirmed the presence of CD8 on alveolar
      macrophages. Interestingly, flow cytometry showed differences between CD8 on
      alveolar macrophages and on T lymphocytes within the ligand binding domain for
      MHC class I. Reverse transcription-PCR analysis on FACS-enriched alveolar
      macrophages showed the presence of CD8alpha mRNA, determining that macrophages
      synthesize CD8. Further studies identified both the alpha (49 +/- 8%)- and beta
      (37 +/- 4%)-chains of CD8 on peritoneal lavage cells (86 +/- 3% macrophages
      (OX42, CD11b)). As with alveolar macrophages, there were differences within the
      ligand-binding domain of CD8 on peritoneal macrophages compared with T
      lymphocytes. Functional studies determined that anti-CD8alpha (OX8) stimulated a
      dose-dependent release of nitric oxide, indicating that CD8 can directly regulate
      macrophage function. Thus, macrophages express an unusual CD8 molecule that
      differs within its ligand-binding domain, compared with T lymphocytes, and these
      findings suggest hitherto unknown ligand(s) for CD8. These findings will lead to
      a greater understanding of macrophage function and regulation.

PMID- 9029124
TI  - Human airway smooth muscle cells express and release RANTES in response to T
      helper 1 cytokines: regulation by T helper 2 cytokines and corticosteroids.
AB  - RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong
      chemotactic activity for eosinophils, lymphocytes, and monocytes. We determined
      the regulation of RANTES production by human airway smooth muscle cells in
      culture. While TNF-alpha, but not IFN-gamma, increased RANTES mRNA expression and
      protein release, the combination of TNF-alpha and IFN-gamma caused a greater
      degree of expression and release in a time- and dose-dependent manner. Sequential
      treatment of airway smooth muscle cells with TNF-alpha and IFN-gamma showed that
      IFN-gamma sensitized the cells to the stimulatory effect of TNF-alpha. Using a
      modified Boyden chamber technique, RANTES separated by reverse-phase liquid
      chromatography from cell culture supernatants of airway smooth muscle cells
      stimulated by TNF-alpha and IFN-gamma showed a strong chemoattractant effect on
      human eosinophils, an effect inhibited by an anti-RANTES Ab. RANTES production
      induced by TNF-alpha and IFN-gamma was inhibited partly by the Th2-derived
      cytokines, IL-4, IL-10, and IL-13, as well as by dexamethasone. Our studies
      indicate that, in addition to contractile responses and mitogenesis, airway
      smooth muscle cells have synthetic and secretory potential with the release of
      RANTES. They may participate in chronic airway inflammation by interacting with
      both Th1- and Th2-derived cytokines to modulate chemoattractant activity for
      eosinophils, activated T lymphocytes, and monocytes/macrophages.

PMID- 9029125
TI  - Stimulation of macrophages by lipopolysaccharide alters the phosphorylation
      state, conformation, and function of PU.1 via activation of casein kinase II.
AB  - We previously reported that LPS stimulation of the RAW264.7 murine macrophage
      cell line rapidly induced a structural change within the N terminus of the
      transcriptional regulatory factor PU.1. PU.1 is required for the expression of a
      variety of cytokine, cytokine receptor, and integrin genes. Western blot analysis
      of nuclear extracts prepared from LPS-stimulated macrophages revealed increased
      phosphorylation of PU.1 at serine residues relative to that in unstimulated
      controls. PU.1-DNA complexes prepared using nuclear extracts from LPS-stimulated
      macrophages were less sensitive to protease digestion compared with PU.1-DNA
      complexes generated using nuclear extracts prepared from unstimulated cells. This
      altered protease sensitivity probably reflects a conformational change within
      PU.1 resulting from LPS-induced phosphorylation. This possibility was supported
      by the finding that in vitro-phosphorylated PU.1 was similarly resistant to
      protease digestion. Transient transfection studies suggest that LPS-induced
      phosphorylation of PU.1 at serine 148, located within a casein kinase II (CKII)
      consensus motif, increases the transactivation function of PU.1. Other
      serine/CKII sites located at positions 41, 45, 132, and 133 do not appear to be
      required for LPS-induced PU.1 function. Lastly, we found that LPS also increased
      the enzymatic activity of CKII in these cells. To our knowledge, these are the
      first studies to demonstrate that LPS can stimulate CKII activity, induce PU.1
      phosphorylation, and enhance the capacity of PU.1 to activate transcription in
      macrophages.

PMID- 9029126
TI  - C5a-dependent up-regulation in vivo of lung vascular P-selectin.
AB  - Acute lung injury in rats following systemic activation of complement by i.v.
      infusion of cobra venom factor (CVF) is known to be P-selectin dependent. In the
      current studies, infusion of CVF caused the appearance in plasma of C5a (as
      revealed by ELISA analysis) together with neutrophil chemotactic activity, which
      was totally blocked by addition in vitro of anti-rat C5a. Using a detector 125I
      labeled antibody to rat P-selectin, we have demonstrated quantitative up
      regulation in vivo of lung vascular P-selectin in a time-dependent manner after
      infusion of CVF. This up-regulation was almost completely blocked by prior
      complement depletion or by the infusion of anti-rat C5a. Platelet depletion did
      not affect CVF-induced up-regulation of lung vascular P-selectin, indicating that
      platelets were not the source of P-selectin. These results demonstrate that
      complement and, specifically, C5a are necessary for up-regulation of lung
      vascular P-selectin after systemic activation of complement.

PMID- 9029127
TI  - Induction of acute inflammatory lung injury by staphylococcal enterotoxin B.
AB  - Superantigens stimulate T lymphocytes at high frequency by interacting with
      appropriate Vbeta segments of the TCR. Challenge of mice with bacterial
      superantigens such as staphylococcal enterotoxin B (SEB) induces the systemic
      release of cytokines resulting in septic shock and death of sensitized animals.
      Analysis of putative pathogenic mechanisms of T cell-dependent septic shock
      revealed that administration of SEB results in acute inflammatory lung injury
      characterized by a profound increase in vascular permeability. Injury was
      associated with marked leukocyte infiltration of the lung and induction of cell
      adhesion molecules including VCAM-1, ICAM-1, and P-selectin, but not E-selectin.
      Lung infiltrating leukocytes consisted of granulocytes, mononuclear phagocytes
      and NK cells with granulocytes representing the major fraction. Consistent with a
      role of neutrophils as cellular mediators of inflammatory organ injury, we
      demonstrate activation of circulating granulocytes in mice treated with SEB. When
      compared with granulocytes of control mice, peripheral blood granulocytes of SEB
      treated mice were found to express increased levels of cell surface Mac-1, to
      down-regulate expression of L-selectin, and to respond with an increased
      production of toxic oxygen metabolites upon exposure to FMLP. Interestingly, TNF
      alpha further enhanced FMLP-induced oxidant production by granulocytes from SEB
      treated but not control mice, suggesting that the systemic response to SEB
      increases granulocyte sensitivity to TNF-alpha-mediated signals. Together, these
      results suggest that acute inflammatory lung injury may contribute to the
      pathogenesis of T cell-dependent lethal shock in mice challenged with bacterial
      superantigens and indicate common pathogenic mechanisms of lung injury induced by
      a large number of distinct inflammatory stimuli.

PMID- 9029128
TI  - Mechanisms of action of antimalarials in inflammation: induction of apoptosis in
      human endothelial cells.
AB  - Antimalarials are beneficial therapeutic agents in systemic lupus and rheumatoid
      arthritis. These autoimmune diseases have abnormally low apoptosis of
      inflammatory cells. Both disorders have an abnormal angiogenesis. In the present
      report, antimalarials were demonstrated to selectively increase apoptosis of
      HUVECs in vitro. A 24-h exposure to 50 or 150 microM of the drugs was associated
      with a significant loss of substrate-adherent cells. Chloroquine exhibited an
      inhibitory effect on HUVEC proliferation over 7 days. Programmed cell death in
      HUVECs rendered nonadherent by chloroquine was confirmed by the induction of DNA
      fragmentation in floating cells. Northern blot analysis revealed a rapidly
      increased expression of the bcl-x(s) gene without any change in the expression of
      the bcl-2 gene, indicating that HUVECs under chloroquine were undergoing
      apoptosis. The onset of the apoptotic cascade in HUVECs appeared shortly after
      the addition of chloroquine. The effect of chloroquine on apoptosis was distinct
      from acute cell lysis and was restricted to HUVECs. Antimalarials also induced IL
      1alpha production. In parallel, chloroquine alone did not increase the expression
      of IL-6. Anti-IL-1alpha Ab or IL-1Ra only marginally reversed chloroquine-induced
      depression of proliferation for the low drug concentration, but not the massive
      cell death effect at and above 50 microM. Taken together, these data may indicate
      that antimalarials repress angiogenesis. The autocrine mechanism involving IL
      1alpha accounts only for a minor fraction of the full antiendothelial effect of
      chloroquine, which is mainly dependent on apoptosis.

PMID- 9029129
TI  - Fibrin induction of ICAM-1 expression in human vascular endothelial cells.
AB  - In acute and chronic inflammatory processes, fibrin deposition, and leukocyte
      accumulation are classic histopathologic hallmarks. Previous studies have shown
      that fibrin and fibrin degradation products can have biologic effects on vascular
      endothelial cells and can induce the expression of several endothelial cell
      derived factors that may be important in regulating inflammation and tissue
      repair. We now demonstrate that coculture of human vascular endothelial cells
      (EC) with fibrin results in the up-regulation of intercellular adhesion molecule
      1 (ICAM-1), thus providing a first link between fibrin deposition and adhesion
      molecule expression, which may lead subsequently to leukocyte accumulation and
      extravasation. Increased ICAM-1 expression was demonstrated by ELISA, flow
      cytometry, and functional adhesion assays. EC ICAM-1 expression increased in a
      time and dose response fashion. Cell surface levels of ICAM-1 induced by fibrin
      were comparable to, or exceeded, levels induced by IL-1beta. ICAM-1 expression
      increased beginning at 4 h post-fibrin formation with sustained elevated
      expression at 48 h. Fibrin-stimulated EC also bound increased numbers of
      polymorphonuclear neutrophils in cellular adhesion assays. This increase in
      adhesion could be blocked by Ab to ICAM-1. Inhibition of fibrin polymerization
      also inhibited the up-regulation of ICAM-1. Culture medium from fibrin-stimulated
      EC contained elevated levels of soluble ICAM-1. These data suggest that fibrin
      deposition on vascular EC, in addition to other reported effects on EC
      metabolism, may also lead to leukocyte accumulation and extravasation through the
      induction of leukocyte adhesion molecules such as ICAM-1.

PMID- 9029130
TI  - Inflammatory cytokines induce endothelial cells to produce and release basic
      fibroblast growth factor and to promote Kaposi's sarcoma-like lesions in nude
      mice.
AB  - Inflammatory cytokines including TNF-alpha, IL-1beta, and IFN-gamma are increased
      in sera and lesions of Kaposi's sarcoma (KS) patients. Previous data have
      indicated that the combination of these cytokines as found in conditioned media
      from activated T cells induces normal endothelial cells to acquire the features
      of KS spindle cells (KS cells) including spindle morphology, marker expression,
      and the responsiveness to the effects of HIV-1 Tat protein. Conditioned media
      from activated T cells or the single cytokines also induce AIDS-KS cells to
      produce and release basic fibroblast growth factor (bFGF). bFGF is highly
      expressed also by in situ KS cells and mediates KS-like lesion formation after
      inoculation of the cells in nude mice. Here we show that both large and small
      vessel endothelial cells chronically exposed to inflammatory cytokines produce
      and release bioactive bFGF in the absence of cell death. In addition, after this
      treatment, endothelial cells acquire angiogenic capability and induce KS-like
      lesions after inoculation in nude mice. Production and release of bFGF is induced
      in a synergistic fashion by TNF-alpha, IL-1beta, and IFN-gamma, and its release
      is further promoted by low cell density and by the serine proteases plasmin and
      thrombin. These results indicate that inflammatory cytokines induce endothelial
      cells to export bFGF and to acquire angiogenic properties, a key feature of the
      KS cell phenotype, and suggest a mechanism by which these cytokines can cooperate
      in the induction of KS.

PMID- 9029131
TI  - A peptide with unique receptor specificity: stimulation of phosphoinositide
      hydrolysis and induction of superoxide generation in human neutrophils.
AB  - Previously, we identified peptides that stimulate phosphoinositide hydrolysis in
      several leukocyte cell lines from mixtures of random hexapeptide sequences.
      Moreover, the peptides activate phospholipase C via a pertussis toxin-sensitive G
      protein-coupled receptor. We now investigate the structure-activity relationship
      of the peptides with the goal of improving the activity of the peptides, as well
      as the biologic function of the peptides. Substitution of the L-methionine at the
      C terminus of peptides with D-methionine markedly increased the effectiveness of
      the peptides. The half-maximal effective concentrations of MKYMPm-NH2 and WKYMVm
      NH2 for stimulation of phosphoinositide hydrolysis in U266 cells were 30 and 0.5
      nM, respectively. By BIAcore analysis we confirmed the existence of a receptor
      for WKYMVm-NH2. Furthermore, the intracellular calcium concentration increase
      induced by WKYMVm-NH2 was not inhibited by several chemoattractants (FMLP, IL-8,
      platelet-activating factor, C5a, granulocyte-macrophage CSF, and granulocyte CSF)
      suggests that WKYMVm-NH2 has a unique cell surface receptor on leukocytes. WKYMVm
      NH2 stimulated the phosphoinositide hydrolysis in U937, HL60, and U266 cells, as
      well as in human neutrophils. Moreover, WKYMVm-NH2 is more effective than FMLP in
      the production of superoxide in human neutrophils. The data suggest that WKYMVm
      NH2 may have the ability to activate the microbicidal functions of human
      neutrophils.

PMID- 9029133
TI  - Characteristic T helper 2 T cell cytokine abnormalities in autoimmune
      lymphoproliferative syndrome, a syndrome marked by defective apoptosis and
      humoral autoimmunity.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is marked by massive
      lymphadenopathy, hepatosplenomegaly, autoimmunity and the presence of increased
      numbers of circulating and tissue TCR-alpha beta, CD4- CD8- T cells. The
      underlying defect is that of decreased T cell and B cell apoptosis, due in most,
      but not all, cases to heterozygous mutations of the Fas gene and corresponding
      defective Fas signaling function. Here we measure in vivo and in vitro cytokine
      secretion in ALPS to shed light on the relation of apoptosis defects to the
      development of autoimmunity. In in vivo studies, ALPS patients manifested greatly
      increased circulating levels of IL-10 (> 100-fold), compared with both healthy
      individuals and various disease controls; in contrast, their levels of IL-1 beta,
      IL-4, and IFN-gamma were normal and their levels of IL-2 and TNF-alpha were
      marginally increased. In parallel in vitro studies, ALPS patients CD4+ DR+ T
      cells stimulated either with anti-CD3/CD28 or anti-CD2/CD28 produced increased
      amounts of IL-4 and IL-5 (10 to 20-fold) and decreased amounts of IFN-gamma (4
      fold) as compared with those of control CD4+ DR+ T cells. In contrast, ALPS
      patients' CD4-/CD8- T cells produced very low amounts of cytokines. Finally, ALPS
      patients' peripheral monocytes/macrophages produced decreased amounts of IL-12
      (30-fold) and increased amounts of IL-10 (5-fold). In conclusion, ALPS is marked
      by the presence of DR+ T cells that exhibit a skewed Th2 cytokine response upon
      various forms of stimulation. This cytokine response, in the presence of
      increased circulating IL-10 levels, is likely to define the cytokine milieu that
      accounts for the humoral autoimmune features of ALPS and, perhaps, of other
      humoral autoimmune states.

PMID- 9029132
TI  - Signaling by adhesion in human neutrophils: activation of the p72syk tyrosine
      kinase and formation of protein complexes containing p72syk and Src family
      kinases in neutrophils spreading over fibrinogen.
AB  - Src family kinases are implicated in signaling by integrins in polymorphonuclear
      neutrophils (PMN). To identify proteins present in complexes with Src family
      kinases, we subjected p58(c-fgr) or p53/56(lyn) immunoprecipitates from Triton X
      100 lysates of PMN incubated on fibrinogen-coated surfaces to in vitro kinase
      assays. Assays on p58(c-fgr) or p53/56(lyn) immunoprecipitates from Triton
      lysates of PMN induced to spread over fibrinogen in response to TNF-alpha showed
      that several proteins form complexes with Src family kinases and can be
      phosphorylated in vitro. Immunoblot analysis showed that the p72(syk) tyrosine
      kinase is one of these proteins. Formation of protein complexes containing Src
      family kinases and p72(syk) required PMN spreading because p72(syk) was not
      detected in p58(c-fgr) or p53/56(lyn) immunoprecipitates from PMN, which were
      stimulated with TNF-alpha, in suspension. In addition, induction of PMN spreading
      with Mn2+ in the absence of TNF-alpha promoted the formation of protein complexes
      containing Src family kinases and p72(syk). We also found that p72(syk)
      autophosphorylating kinase activity was enhanced, and a fraction of p72(syk) was
      translocated to a Triton-insoluble cytoskeletal fraction in PMN induced to spread
      over fibrinogen by TNF-alpha or Mn2+. In vitro kinase assays on CD18 (beta 2
      integrin subunit) immunoprecipitates from Triton lysates of spread PMN showed
      that several proteins formed complexes with CD18 and could be phosphorylated in
      vitro. Immunoblot analysis of CD18 immunoprecipitates allowed us to identify
      p72(syk) as one of these proteins. These findings show that PMN spreading is
      accompanied by activation of p72(syk) and formation of multimolecular complexes
      in which Src family kinases and p72(syk) colocalize.

PMID- 9029135
TI  - Studies on the interaction of IL-8 with human plasma alpha 2-macroglobulin:
      evidence for the presence of IL-8 complexed to alpha 2-macroglobulin in lung
      fluids of patients with adult respiratory distress syndrome.
AB  - alpha 2-Macroglobulin (alpha 2m) is a major plasma proteinase inhibitor, as well
      as a carrier and regulator of the function of many cytokines. IL-8 is a potent
      neutrophil attractant and activator, and it plays an important role in the
      pathogenesis of adult respiratory distress syndrome (ARDS). The concentration of
      both IL-8 and alpha 2m is increased in lung fluids from patients with ARDS.
      Therefore, interaction of IL-8 with human alpha 2m was studied. Mixtures of
      native and methylamine-treated alpha 2m (fast alpha 2m) with 125I-labeled IL-8
      were analyzed using nonreducing gel electrophoresis. 125I-labeled IL-8
      exclusively bound to fast alpha 2m, and the binding could be inhibited by
      unlabeled IL-8. Analysis of the IL-8-alpha 2m interaction using SDS-PAGE gels
      indicated that the binding was mainly noncovalent. The affinity of the binding of
      alpha 2m to IL-8 was measured using an equilibrium dialysis technique, and Kd was
      30 nM. Bioassays revealed that fast alpha 2m did not affect IL-8-induced
      neutrophil degranulation or chemotaxis. However, it protected IL-8 from
      proteolytic degradation. In addition, IL-8 complexed to alpha 2m was detected in
      lung fluids from patients with ARDS. alpha 2m may therefore modulate IL-8
      function in the lung.

PMID- 9029134
TI  - Human anti-nicotinic acetylcholine receptor recombinant Fab fragments isolated
      from thymus-derived phage display libraries from myasthenia gravis patients
      reflect predominant specificities in serum and block the action of pathogenic
      serum antibodies.
AB  - Myasthenia gravis (MG) is a prototype Ab-mediated autoimmune disease in which Abs
      against nicotinic acetylcholine receptors (AChR) induce loss of functional
      receptors at the neuromuscular junction. Germinal centers present in MG
      hyperplastic thymus contain activated B cells spontaneously producing anti-human
      AChR (anti-huAChR) Ab in vitro. To access the anti-huAChR repertoire, phage
      display Fab libraries of thymic lymphocytes were constructed from two MG
      patients. Four Fabs highly specific for huAChR were isolated that bind to
      determinants in or near the main immunogenic region. These anti-huAChR Fabs
      showed evidence of significant somatic mutations, supporting the idea that the
      anti-huAChR Ab response in MG patients is driven by Ag. Two Fabs were able to
      inhibit up to 90% of donor serum anti-huAChR Abs. Competition with serum anti
      huAChR Ab was also observed in unrelated MG patients and indicate that anti
      huAChR Fabs bind to epitopes on huAChR recognized by the majority of MG patients.
      In vitro antigenic modulation studies demonstrated that anti-huAChR Fabs were
      able to induce AChR loss when cross-linked by an anti-Fab Ab but not as
      monovalent Fab. Moreover, anti-huAChR Fabs were able to protect against AChR loss
      by antigenic modulation induced by MG serum Abs, suggesting a potential
      therapeutic role for these recombinant Fabs in patients with a myasthenic crisis.

PMID- 9029136
TI  - Analysis of human common bile duct-associated T cells: evidence for
      oligoclonality, T cell clonal persistence, and epithelial cell recognition.
AB  - The phenotype of T cells associated with the common bile duct (CBD) is unknown.
      We investigated the hypothesis that they behave like other intraepithelial
      lymphocytes (IEL). Thus, we sought to determine the phenotype, TCR repertoire,
      and epithelial recognition of T cells obtained during endoscopic retrograde
      cholangiopancreatography. Three subjects were studied: two with primary
      sclerosing cholangitis and one normal control. After establishing a short-term T
      cell line, cells were 1) stained with mAbs for flow cytometric analysis, 2)
      analyzed for TCRB chain transcript expression, and 3) used as effector cells for
      cytotoxicity and proliferation. Flow cytometry revealed that for all the subjects
      98% of the T cells were TCR-alpha beta-positive. Immunohistology of the CBD
      showed that the epithelium and lamina propria contained significant numbers of
      CD3+ CD43+ CD45RO+ lymphocytes. Complementarity-determining region 3 length
      displays suggested that the CBD-derived lines were oligoclonal. This was
      confirmed by cloning and random sequencing of PCR amplification products using
      TCRBV region family-specific primers; TCRB chain sequences were reiterated in all
      transcripts analyzed. In one case, two expanded TCRB clones could be identified
      that were persistent in the bile duct over a 1-yr period. The CBD-derived lines
      were cytolytic in a redirected lysis assay and caused cytolysis of an intestinal
      epithelial cell line (Caco-2). This recognition was likely preferential for
      intestinal epithelial cells, since a CBD-derived line exhibited proliferation to
      two intestinal epithelial cell lines (HT-29 and Caco-2) but not three other lines
      (HepG2, human foreskin fibroblast, and KD). We conclude that the CBD contains
      IELs that share several characteristics with intestinal IELs.

PMID- 9029137
TI  - Human T cell responses induced by vaccination with Mycobacterium bovis bacillus
      Calmette-Guerin.
AB  - Many aspects of the widely used bacillus Calmette-Guerin (BCG) vaccine against
      tuberculosis are still the subject of controversy. There is a huge variation in
      efficacy from one clinical trial to another and no relationship between vaccine
      induced skin test conversion and subsequent protection. We have studied in vitro
      cell-mediated immune responses primed by BCG vaccination in 22 healthy Danish
      donors with different levels of in vitro purified protein derivative (PPD)
      reactivity before vaccination. The study demonstrated a markedly different
      development of reactivity to mycobacterial Ags depending on the prevaccination
      sensitivity to PPD. Previously sensitized donors mounted a potent and highly
      accelerated recall response within the first week of BCG vaccination.
      Nonsensitized donors, in contrast, exhibited a gradually increasing
      responsiveness to mycobacterial Ags, reaching maximal levels between day 56 and
      365 postvaccination. The recognition of different classes of Ags were induced in
      a stepwise manner: culture filtrate Ags were recognized 1 wk postvaccination
      followed by cell wall, membrane, and the cytosolic Ag fraction. The T cell
      response primed by BCG vaccination was characterized as a CD4 response with a Th1
      like cytokine pattern and substantial levels of Ag-specific cytotoxicity. The
      specificity of the T cell response generated was broad and directed to a range of
      culture filtrate Ag fractions. The study shows that BCG vaccination of previously
      nonsensitized donors can provide important data on potentially protective immune
      responses in humans and suggest a careful evaluation of prevaccination
      sensitivity when investigating vaccine-induced immunity.

PMID- 9029138
TI  - C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial
      meningitis and mediate chemotactic activity on peripheral blood-derived
      polymorphonuclear and mononuclear cells in vitro.
AB  - The appearance of polymorphonuclear and mononuclear leukocytes in the
      cerebrospinal fluid (csf) is an important hallmark of bacterial meningitis.
      Chemokines are candidate mediators of cell migration from blood into the
      subarachnoid space. Therefore, concentrations of C-X-C and C-C chemokines in the
      csf of patients with pyogenic meningitis were measured by ELISA. Highly
      significant elevations of chemokine levels in comparison with noninflammatory csf
      controls were found for IL-8 (median, 21.6 ng/ml; range, < 0.1 to 191.3), growth
      related gene product alpha (median, 5.6 ng/ml; range, < 0.1 to 48.2), monocyte
      chemotactic protein-1 (median, 26.4 ng/ml; range, < 0.2 to 193.8), macrophage
      inflammatory protein-1 alpha (MIP-1 alpha; median, 1.8 ng/ml; range, < 0.5 to
      18.0), MIP-1 beta (median, 10.6 ng/ml; range, < 0.3 to 84.4), but not for RANTES
      (regulated upon activation, normal T cell expressed and secreted). The csf of
      bacterial meningitis were chemotactic for neutrophils and mononuclear leukocytes.
      Correlation analysis demonstrated a strong association between individual
      chemokine levels and chemotactic activity mediated by csf. A significant
      reduction of neutrophil chemotaxis was obtained by anti-IL-8 and anti-growth
      related gene product alpha Abs, and a reduction of mononuclear cell migration was
      achieved by a combination of anti-monocyte chemotactic protein-1, anti-MIP-1
      alpha, and anti-MIP-1 beta Abs. Since no significant correlation was found
      between csf leukocyte counts and chemokine concentrations or chemotactic activity
      mediated by csf, additional factors influence the extent of pleocytosis in vivo.

PMID- 9029139
TI  - T cell receptor of Fas-sensitive T cells in rheumatoid synovium.
AB  - Apoptosis is found in synoviocytes and CD3+ T cells in the synovium of patients
      with rheumatoid arthritis (RA). To analyze the pathogenesis of apoptosis in
      rheumatoid synovium, we examined the expression of Fas Ag, Fas ligand (Fas-L),
      and TCR on T cells susceptible to anti-Fas mAbs. Fas Ag is expressed on 40 to 60%
      of CD3+ T cells in the synovium as measured by immunohistochemical and flow
      cytometry methods. It was observed by the reverse transcription-PCR method that
      Fas-L is overexpressed on T cells infiltrating the rheumatoid synovium. These
      results suggest that apoptosis in RA synovium is mediated by the Fas/Fas-L
      pathway. PCR-single-strand conformation polymorphism clearly demonstrated that
      more than 50% of T cells that accumulate in synovium are removed by incubation
      with anti-Fas mAbs for 24 h in vitro, indicating that these cells are Fas
      sensitive. Junctional sequence analysis revealed several conserved amino acids
      motifs (ERxxxSMNTE, IAAEGLLG, QxEGxD, VPD, TLAGxYNEQ, EPSE, LTNxGEL, QGK, NIP,
      GLL, and KWT) in the CDR3 region of accumulated Fas-sensitive T cell clones,
      whereas these motifs were not detected in Fas-resistant clones. In conclusion,
      our findings support the notion that Fas-sensitive T cells in rheumatoid synovium
      are generated by Ag stimulation and recognize relatively limited T cell epitopes
      on autoantigens, suggesting that susceptibility to anti-Fas mAbs might be a
      selection marker for activated autoreactive T cells in RA.

PMID- 9029140
TI  - Effects of IL-10 on systemic inflammatory responses during sublethal primate
      endotoxemia.
AB  - IL-10 protects mice from LPS-induced lethality. To determine the effects of IL-10
      on LPS-induced inflammatory responses, six Papio anubis baboons were i.v.
      injected with a sublethal dose of LPS (Salmonella typhimurium; 500 microg/kg)
      directly preceded by either human rIL-10 (n = 3, 500 microg/kg) or diluent (n =
      3). IL-10 strongly inhibited LPS-induced release of TNF, IL-6, IL-8, and IL-12
      (all p < 0.05). By contrast, IL-10 did neither influence the activation of the
      coagulation system (plasma levels of thrombin/antithrombin III complexes), nor
      the activation of the fibrinolytic system (plasma levels of tissue-type
      plasminogen activator, plasminogen activator inhibitor type I, and plasmin/alpha
      2-antiplasmin complexes). IL-10 modestly attenuated neutrophilic leukocytosis and
      neutrophil degranulation (plasma concentrations of elastase/alpha1-antitrypsin
      complexes) (both p < 0.05). Changes in surface TNF receptor expression on
      circulating granulocytes were not affected by IL-10. These results suggest that
      during sublethal endotoxemia the predominant anti-inflammatory effect of IL-10
      treatment is inhibition of proinflammatory cytokine release.

PMID- 9029141
TI  - Lipoprotein from Yersinia enterocolitica contains epitopes that cross-react with
      the human thyrotropin receptor.
AB  - Yersinia enterocolitica has recently been shown to produce a low molecular mass
      envelope protein that contains an epitope(s) that is cross-reactive with the
      extracellular domain of the human thyrotropin receptor (ETSHR). In this study, we
      have generated mAb to this cross-reactive protein and have obtained amino acid
      sequences for peptide fragments obtained from Lys-c digestion of the protein. The
      amino acid sequences of these peptides were identical to sequences present in
      bacterial lipoprotein (LP). All bacteria of the Enterobacteriaceae family produce
      LP as a major outer membrane protein. However, the ETSHR cross-reactive
      epitope(s) was shown to be unique to LP produced by Yersinia species. This was
      shown by Western blot analysis using a mAb specific for LP and with affinity
      purified Ab specific for either LP or ETSHR and obtained from mouse antiserum
      generated to Y. enterocolitica. LPs from different Gram-negative bacteria were
      shown to be mitogenic for C3H/HeJ spleen cells and induced production and
      secretion of significant levels of Ig. Production of Ab that recognized the ETSHR
      was only induced in spleen cells stimulated with the LP obtained from Yersinia.
      In contrast, LP was not mitogenic for either human PBMC or human B cells.
      However, LP did induce IL6 and IL8 production in human monocytes at levels
      equivalent to that seen after LPS activation. These results identify, for the
      first time, the Yersinia envelope protein that is cross-reactive with the ETSHR
      and show that it can activate human monocytes. These findings are potentially
      important for advancing our understanding of the role molecular mimicry plays in
      the induction of autoimmunity to the thyrotropin receptor.

PMID- 9029142
TI  - Molecular structure of the sarcomeric M band: mapping of titin and myosin binding
      domains in myomesin and the identification of a potential regulatory
      phosphorylation site in myomesin.
AB  - The M band of sarcomeric muscle is a highly complex structure which contributes
      to the maintenance of the regular lattice of thick filaments. We propose that the
      spatial coordination of this assembly is regulated by specific interactions of
      myosin filaments, the M band protein myomesin and the large carboxy-terminal
      region of titin. Corresponding binding sites between these proteins were
      identified. Myomesin binds myosin in the central region of light meromyosin (LMM,
      myosin residues 1506-1674) by its unique amino-terminal domain My1. A single
      titin immunoglobulin domain, m4, interacts with a myomesin fragment spanning
      domains My4-My6. This interaction is regulated by phosphorylation of Ser482 in
      the linker between myomesin domains My4 and My5. Myomesin phosphorylation at this
      site by cAMP-dependent kinase and similar or identical activities in muscle
      extracts block the association with titin. We propose that this demonstration of
      a phosphorylation-controlled interaction in the sarcomeric cytoskeleton is of
      potential relevance for sarcomere formation and/or turnover. It also reveals how
      binding affinities of modular proteins can be regulated by modifications of inter
      domain linkers.

PMID- 9029143
TI  - Binding of non-native protein to Hsp25 during heat shock creates a reservoir of
      folding intermediates for reactivation.
AB  - Small heat shock proteins (sHsps) are a conserved and ubiquitous protein family.
      Their ability to convey thermoresistance suggests their participation in
      protecting the native conformation of proteins. However, the underlying
      functional principles of their protective properties and their role in concert
      with other chaperone families remain enigmatic. Here, we analysed the influence
      of Hsp25 on the inactivation and subsequent aggregation of a model protein,
      citrate synthase (CS), under heat shock conditions in vitro. We show that stable
      binding of several non-native CS molecules to one Hsp25 oligomer leads to an
      accumulation of CS unfolding intermediates, which are protected from irreversible
      aggregation. Furthermore, a number of different proteins which bind to Hsp25 can
      be isolated from heat-shocked extracts of cells. Under permissive folding
      conditions, CS can be released from Hsp25 and, in cooperation with Hsp70, an ATP
      dependent chaperone, the native state can be restored. Taken together, our
      findings allow us to integrate sHsps functionally in the cellular chaperone
      system operating under heat shock conditions. The task of sHsps in this context
      is to efficiently trap a large number of unfolding proteins in a folding
      competent state and thus create a reservoir of non-native proteins for an
      extended period of time, allowing refolding after restoration of physiological
      conditions in cooperation with other chaperones.

PMID- 9029144
TI  - Crk is required for apoptosis in Xenopus egg extracts.
AB  - Apoptosis is essential for the development and homeostasis of multicellular
      organisms. Recently, a cell-free extract prepared from Xenopus eggs was shown to
      recapitulate intracellular apoptotic pathways in vitro. While many stimuli have
      been shown to trigger apoptosis in a variety of cell types, the intracellular
      signaling pathways involved in apoptosis remain largely unknown. Here we show
      that addition of a recombinant protein containing the phosphotyrosine binding
      (SH2) domain from the adaptor protein crk, but not those derived from a panel of
      other signaling proteins, can prevent apoptosis in the Xenopus egg extract
      system. Furthermore, immunodepletion of endogenous crk protein from the egg
      extracts, or addition of anti-crk antisera to these extracts, prevents apoptosis.
      The ability to undergo apoptosis can be restored to these extracts by addition of
      recombinant crk protein. These results directly demonstrate that crk participates
      in apoptotic signaling.

PMID- 9029145
TI  - Micromolar and submicromolar Ca2+ spikes regulating distinct cellular functions
      in pancreatic acinar cells.
AB  - Agonists induce Ca2+ spikes, waves and oscillations initiating at a trigger zone
      in exocrine acinar cells via Ca2+ release from intracellular Ca2+ stores. Using a
      low affinity ratiometric Ca2+ indicator dye, benzothiazole coumarin (BTC), we
      found that high concentrations of agonists transiently increased Ca2+
      concentrations to the micromolar range (>10 microM) in the trigger zone.
      Comparison with results obtained with a high affinity Ca2+ indicator dye, fura-2,
      indicated that fura-2 was in fact saturated with Ca2+ during the agonist-induced
      Ca2+ spikes in the trigger zone. We further revealed that the micromolar Ca2+
      spikes were necessary for inducing exocytosis of zymogen granules investigated
      using capacitance measurements. In contrast, submicromolar Ca2+ spikes
      selectively gave rise to sequential activation of luminal and basal ion channels.
      These results suggest new functional diversity in Ca2+ spikes and a critical role
      for the micromolar Ca2+ spikes in exocytotic secretion from exocrine acinar
      cells. Our data also emphasize the value of investigating the Ca2+ signalling
      using low affinity Ca2+ indicators.

PMID- 9029146
TI  - Rapid Ca2+-mediated activation of Rap1 in human platelets.
AB  - Rap1 is a small, Ras-like GTPase whose function and regulation are still largely
      unknown. We have developed a novel assay to monitor the active, GTP-bound form of
      Rap1 based on the differential affinity of Rap1GTP and Rap1GDP for the Rap
      binding domain of RalGDS (RBD). Stimulation of blood platelets with alpha
      thrombin or other platelet activators caused a rapid and strong induction of Rap1
      that associated with RBD in vitro. Binding to RBD increased from undetectable
      levels in resting platelets to >50% of total Rap1 within 30 s after stimulation.
      An increase in the intracellular Ca2+ concentration is both necessary and
      sufficient for Rap1 activation since it was induced by agents that increase
      intracellular Ca2+ and inhibited by a Ca2+-chelating agent. Neither inhibition of
      translocation of Rap1 to the cytoskeleton nor inhibition of platelet aggregation
      affected thrombin-induced activation of Rap1. In contrast, prostaglandin I2
      (PGI2), a strong negative regulator of platelet function, inhibited agonist
      induced as well as Ca2+-induced activation of Rap1. From our results, we conclude
      that Rap1 activation in platelets is an important common event in early agonist
      induced signalling, and that this activation is mediated by an increased
      intracellular Ca2+ concentration.

PMID- 9029147
TI  - A protein-arginine methyltransferase binds to the intracytoplasmic domain of the
      IFNAR1 chain in the type I interferon receptor.
AB  - The intracytoplasmic domain (IC) of cytokine receptors provides docking sites for
      proteins which mediate signal transduction. Thus, in interferon-alpha,beta
      receptors (IFNAR1 and 2), the IC region binds protein-tyrosine and 
      serine/threonine kinases which phosphorylate the receptor and the associated Stat
      transcription factors. A two-hybrid screening was carried out to identify
      additional proteins which could interact with the IC domain of the IFNAR1 chain
      of the IFN-alpha,beta receptor. Several positive clones representing a protein
      sequence designated IR1B4 were recovered from a human cDNA library. IR1B4 was
      identified as the human homolog of PRMT1, a protein-arginine methyltransferase
      from rat cells. Flag-IR1B4 fusion proteins bind to the isolated IFNAR1
      intracytoplasmic domain produced in Escherichia coli, as well as to the intact
      IFNAR1 chain extracted by detergent from human U266 cell membranes. S
      Adenosylmethionine-dependent methyltransferase activity was precipitated by anti
      IFNAR1 antibodies from untreated human cells. IR1B4/PRMT1 is involved in IFN
      action since U266 cells rendered deficient in this methyltransferase by antisense
      oligonucleotides become more resistant to growth inhibition by IFN. Methylation
      of proteins by enzymes which can attach to the IC domains of receptors may be a
      signaling mechanism complementing protein phosphorylation. Among substrates
      methylated by PRMT1 are RNA-binding heterogeneous nuclear ribonucleoproteins
      (hnRNPs) which are involved in mRNA processing, splicing and transport into the
      cytoplasm.

PMID- 9029148
TI  - The glucocorticoid receptor is a key regulator of the decision between self
      renewal and differentiation in erythroid progenitors.
AB  - During development and in regenerating tissues such as the bone marrow,
      progenitor cells constantly need to make decisions between proliferation and
      differentiation. We have used a model system, normal erythroid progenitors of the
      chicken, to determine the molecular players involved in making this decision. The
      molecules identified comprised receptor tyrosine kinases (c-Kit and c-ErbB) and
      members of the nuclear hormone receptor superfamily (thyroid hormone receptor and
      estrogen receptor). Here we identify the glucocorticoid receptor (GR) as a key
      regulator of erythroid progenitor self-renewal (i.e. continuous proliferation in
      the absence of differentiation). In media lacking a GR ligand or containing a GR
      antagonist, erythroid progenitors failed to self-renew, even if c-Kit, c-ErbB and
      the estrogen receptor were activated simultaneously. To induce self-renewal, the
      GR required the continuous presence of an activated receptor tyrosine kinase and
      had to cooperate with the estrogen receptor for full activity. Mutant analysis
      showed that DNA binding and a functional AF-2 transactivation domain are required
      for proliferation stimulation and differentiation arrest. c-myb was identified as
      a potential target gene of the GR in erythroblasts. It could be demonstrated that
      delta c-Myb, an activated c-Myb protein, can functionally replace the GR.

PMID- 9029149
TI  - Two EGF molecules contribute additively to stabilization of the EGFR dimer.
AB  - Receptor dimerization is generally considered to be the primary signaling event
      upon binding of a growth factor to its receptor at the cell surface. Little,
      however, is known about the precise molecular details of ligand-induced receptor
      dimerization, except for studies of the human growth hormone (hGH) receptor. We
      have analyzed the binding of epidermal growth factor (EGF) to the extracellular
      domain of its receptor (sEGFR) using titration calorimetry, and the resulting
      dimerization of sEGFR using small-angle X-ray scattering. EGF induces the
      quantitative formation of sEGFR dimers that contain two EGF molecules. The data
      obtained from the two approaches suggest a model in which one EGF monomer binds
      to one sEGFR monomer, and that receptor dimerization involves subsequent
      association of two monomeric (1:1) EGF-sEGFR complexes. Dimerization may result
      from bivalent binding of both EGF molecules in the dimer and/or receptor-receptor
      interactions. The requirement for two (possibly bivalent) EGF monomers
      distinguishes EGF-induced sEGFR dimerization from the hGH and interferon-gamma
      receptors, where multivalent binding of a single ligand species (either monomeric
      or dimeric) drives receptor oligomerization. The proposed model of EGF-induced
      sEGFR dimerization suggests possible mechanisms for both ligand-induced homo- and
      heterodimerization of the EGFR (or erbB) family of receptors.

PMID- 9029150
TI  - Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular
      stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3
      and SAPK2 (RK/p38).
AB  - Stress-activated protein kinase-3 (SAPK3), a recently described MAP kinase family
      member with a wide-spread tissue distribution, was transfected into several
      mammalian cell lines and shown to be activated in response to cellular stresses,
      interleukin-1 (IL-1) and tumour necrosis factor (TNF) in a similar manner to
      SAPK1 (also termed JNK) and SAPK2 (also termed p38, RK, CSBP and Mxi2). SAPK3 and
      SAPK2 were activated at similar rates in vitro by SAPKK3 (also termed MKK6), and
      SAPKK3 was the only activator of SAPK3 that was induced when KB or 293 cells were
      exposed to cellular stresses or stimulated with IL-1 or TNF. Co-transfection with
      SAPKK3 induced SAPK3 activity and greatly enhanced activation in response to
      osmotic shock. These experiments indicate that SAPKK3 mediates the activation of
      SAPK3 in several mammalian cells. SAPK3 and SAPK2 phosphorylated a number of
      proteins at similar rates, including the transcription factors ATF2, Elk-1 and
      SAP1, but SAPK3 was far less effective than SAPK2 in activating MAPKAP kinase-2
      and MAPKAP kinase-3. Unlike SAPK2, SAPK3 was not inhibited by the drug SB 203580.
      SAPK3 phosphorylated ATF2 at Thr69, Thr71 and Ser90, the same residues
      phosphorylated by SAPK1, whereas SAPK2 only phosphorylated Thr69 and Thr71. Our
      results suggest that cellular functions previously attributed to SAPK1 and/or
      SAPK2 may be mediated by SAPK3.

PMID- 9029151
TI  - Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of
      oligodendrocyte differentiation.
AB  - Many types of vertebrate precursor cells divide a limited number of times before
      they stop and terminally differentiate. In no case is it known what causes them
      to stop dividing. We have been studying this problem in the proliferating
      precursor cells that give rise to postmitotic oligodendrocytes, the cells that
      make myelin in the central nervous system. We show here that two components of
      the cell cycle control system, cyclin D1 and the Cdc2 kinase, are present in the
      proliferating precursor cells but not in differentiated oligodendrocytes,
      suggesting that the control system is dismantled in the oligodendrocytes. More
      importantly, we show that the cyclin-dependent kinase (Cdk) inhibitor p27
      progressively accumulates in the precursor cells as they proliferate and is
      present at high levels in oligodendrocytes. Our findings are consistent with the
      possibility that the accumulation of p27 is part of both the intrinsic counting
      mechanism that determines when precursor cell proliferation stops and
      differentiation begins and the effector mechanism that arrests the cell cycle
      when the counting mechanism indicates it is time. The recent findings of others
      that p27-deficient mice have an increased number of cells in all of the organs
      examined suggest that this function of p27 is not restricted to the
      oligodendrocyte cell lineage.

PMID- 9029152
TI  - Abrogation of a mitotic checkpoint by E2 proteins from oncogenic human
      papillomaviruses correlates with increased turnover of the p53 tumor suppressor
      protein.
AB  - Human papillomavirus (HPV) E2 and E1 proteins are required for the replication of
      viral genomes in vivo. We have examined the effects of increasing the level of E2
      on viral and cellular replication using recombinant adenoviruses. Infection of
      cells which maintain HPV 31 DNA episomally with E2 recombinant adenoviruses
      resulted in a 5-fold increase in genome copy number as well as an S phase arrest
      allowing for the continued replication of cellular DNA. Similar effects on cell
      cycle progression were seen following infection of normal human foreskin
      keratinocytes, the natural host cell. The DNA content of these cells increased
      beyond 4N indicating that multiple rounds of replication had occurred without an
      intervening mitotic event. In addition, increased cyclin A and E associated
      kinase activity was observed, while no change was detected in cyclin B associated
      kinase activity or in the activation state of cdc2 kinase. Interestingly, the
      levels of the p53 tumor suppresser protein were dramatically reduced through a
      post-transcriptional mechanism following infection. These data suggest a role for
      E2 in regulating viral and cellular replication by abrogation of a mitotic
      checkpoint, which is, at least in part, controlled by p53.

PMID- 9029153
TI  - Cdk2-dependent phosphorylation of Id2 modulates activity of E2A-related
      transcription factors.
AB  - The helix-loop-helix (HLH) protein Id2 is thought to affect the balance between
      cell growth and differentiation by negatively regulating the function of basic
      helix-loop-helix (bHLH) transcription factors. Id2 acts by forming heterodimers
      that are unable to bind to specific (E-box) DNA sequences. Here we show that this
      activity can be overcome by phosphorylation of a serine residue within a
      consensus target site for cyclin-dependent kinases (Cdks). In vitro, Id2 can be
      phosphorylated by either cyclin E-Cdk2 or cyclin A-Cdk2 but not by cyclin D
      dependent kinases. Analogous phosphorylation occurs in serum-stimulated human
      diploid fibroblasts at a time in late G1 consistent with the appearance of active
      cyclin E-Cdk2. The phosphorylation of Id2 in these cells correlates with the
      restoration of a distinct E-box-dependent DNA-binding complex, suggesting that
      the levels of this complex are modulated by both the abundance and
      phosphorylation status of Id2. These data provide a link between cyclin-dependent
      kinases and bHLH transcription factors that may be critical for the regulation of
      cell proliferation and differentiation.

PMID- 9029154
TI  - Dual phosphorylation of the T-loop in cdk7: its role in controlling cyclin H
      binding and CAK activity.
AB  - A cyclin-dependent kinase (cdk)-activating kinase (CAK) has been shown previously
      to catalyze T-loop phosphorylation of cdks in most eukaryotic cells. This enzyme
      exists in either of two forms: the major one contains cdk7, cyclin H and an
      assembly factor called MAT-1, whilst the minor one lacks MAT-1. Cdk7 is unusual
      among cdks because it contains not one but two residues (S170 and T176 in Xenopus
      cdk7) in its T-loop that are phosphorylated in vivo. We have investigated the
      role of S170 and T176 phosphorylation in the assembly and activity of cyclin H
      cdk7 dimers. In the absence of MAT-1, phosphorylation of the T-loop appears to be
      required for cdk7 to bind cyclin H. Phosphorylation of both residues does not
      require cyclin H binding in vitro. Phosphorylation of S170 is sufficient for cdk7
      to bind cyclin H with low affinity, but high affinity binding requires T176
      phosphorylation. By mutational analysis, we demonstrate that in addition to its
      role in promotion of cyclin H binding, S170 phosphorylation plays a direct role
      in the control of CAK activity. Finally, we show that dual phosphorylation of
      S170 and T176, or substitution of both phosphorylatable residues by aspartic
      residues, is sufficient to generate CAK activity to one-third of its maximal
      value in vitro, even in the absence of cyclin H and MAT-1, and may thus provide
      further clues as to how cyclins activate cdk subunits.

PMID- 9029155
TI  - Over-expression of GATA-6 in Xenopus embryos blocks differentiation of heart
      precursors.
AB  - Xenopus GATA-6 transcripts are first detected at the beginning of gastrulation in
      the mesoderm, and subsequent domains of expression include the field of cells
      shown to have heart-forming potential. In this region, GATA-6 expression
      continues only in those cells that go on to form the heart; however, a decrease
      occurs prior to terminal differentiation. Artificial elevation of GATA-6, but not
      GATA-1, prevents expression of both cardiac actin and heart-specific myosin light
      chain. This effect is heart-specific because cardiac actin expression is
      unaffected in somites. Expression of the earlier marker XNkx-2.5 was unaffected
      and morphological development of the heart was initiated independently of the
      establishment of the contractile machinery. We conclude that a reduction in the
      level of GATA-6 is important for the progression of the cardiomyogenic
      differentiation programme and that GATA-6 may act to maintain heart cells in the
      precursor state. At later stages, when the elevated GATA-6 levels had decayed,
      differentiation ensued but the number of cells contributing to the myocardium had
      increased, suggesting either that the blocked cells had proliferated or that
      additional cells had been recruited.

PMID- 9029156
TI  - p300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene
      transcription.
AB  - The nuclear phosphoprotein p300 is a new member of a family of 'co-activators'
      (which also includes the CREB binding protein CBP), that directly modulate
      transcription by interacting with components of the basal transcriptional
      machinery. Both p300 and CBP are targeted by the adenovirus E1A protein, and
      binding to p300 is required for E1A to inhibit terminal differentiation in both
      keratinocytes and myoblasts. Here we demonstrate that, in differentiating
      skeletal muscle cells, p300 physically interacts with the myogenic basic helix
      loop-helix (bHLH) regulatory protein MyoD at its DNA binding sites. During muscle
      differentiation, MyoD plays a dual role: besides activating muscle-specific
      transcription, it induces permanent cell cycle arrest by up-regulating the cyclin
      dependent kinase inhibitor p21. We show that p300 is involved in both these
      activities. Indeed, E1A mutants lacking the ability to bind p300 are greatly
      impaired in the repression of E-box-driven transcription, and p300 overexpression
      rescues the wild-type E1A-mediated repression. Moreover, p300 potentiates MyoD-
      and myogenin-dependent activation of transcription from E-box-containing reporter
      genes. We also provide evidence, obtained by microinjection of anti-p300
      antibodies, that p300 is required for MyoD-dependent cell cycle arrest in either
      myogenic cells induced to differentiate or in MyoD-converted C3H10T1/2
      fibroblasts, but is dispensable for maintenance of the postmitotic state of
      myotubes.

PMID- 9029157
TI  - Conversion of ectoderm into a neural fate by ATH-3, a vertebrate basic helix-loop
      helix gene homologous to Drosophila proneural gene atonal.
AB  - We have isolated a novel basic helix-loop-helix (bHLH) gene homologous to the
      Drosophila proneural gene atonal, termed ATH-3, from Xenopus and mouse. ATH-3 is
      expressed in the developing nervous system, with high levels of expression in the
      brain, retina and cranial ganglions. Injection of ATH-3 RNA into Xenopus embryos
      dramatically expands the neural tube and induces ectopic neural tissues in the
      epidermis but inhibits non-neural development. This ATH-3-induced neural
      hyperplasia does not require cell division, indicating that surrounding cells
      which are normally non-neural types adopt a neural fate. In a Xenopus animal cap
      assay, ATH-3 is able to convert ectodermal cells into neurons expressing anterior
      markers without inducing mesoderm. Interestingly, a single amino acid change from
      Ser to Asp in the basic region, which mimics phosphorylation of Ser, severely
      impairs the anterior marker-inducing ability without affecting general neurogenic
      activities. These results provide evidence that ATH-3 can directly convert non
      neural or undetermined cells into a neural fate, and suggest that the Ser residue
      in the basic region may be critical for the regulation of ATH-3 activity by
      phosphorylation.

PMID- 9029158
TI  - The Xenopus RNA polymerase I transcription factor, UBF, has a role in
      transcriptional enhancement distinct from that at the promoter.
AB  - Repeated sequence elements found upstream of the ribosomal gene promoter in
      Xenopus function as RNA polymerase I-specific transcriptional enhancers. Here we
      describe an in vitro system in which these enhancers function in many respects as
      in vivo. The principal requirement for enhancer function in vitro is the presence
      of a high concentration of upstream binding factor (UBF). This system is utilized
      to demonstrate that enhancers function by increasing the probability of a stable
      transcription complex forming on the adjacent promoter. Species differences in
      UBF are utilized to demonstrate that enhancers do not act by recruiting UBF to
      the promoter, rather UBF performs its own distinct role at the enhancers. UBF
      function in enhancement differs from that at the promoter, as it is flexible with
      respect to both the species of UBF and the enhancer element employed.
      Additionally, we identify a potential role for the mammalian UBF splice variant,
      UBF2, in enhancer function. We demonstrate that the TATA box binding protein
      (TBP)-containing component of Xenopus RNA polymerase I transcription, Rib1, can
      interact with an enhancer-UBF complex. This suggests a model in which enhancers
      act by recruiting Rib1 to the promoter.

PMID- 9029159
TI  - Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion
      in the PKR gene: role of IRF-1 and NF-kappaB.
AB  - The interferon (IFN)-induced double-stranded RNA (dsRNA)-activated Ser/Thr
      protein kinase (PKR) plays a role in the antiviral and antiproliferative effects
      of IFN. PKR phosphorylates initiation factor eIF2alpha, thereby inhibiting
      protein synthesis, and also activates the transcription factor, nuclear factor
      kappaB (NF-kappaB), by phosphorylating the inhibitor of NF-kappaB, IkappaB. Mice
      devoid of functional PKR (Pkr(o/o)) derived by targeted gene disruption exhibit a
      diminished response to IFN-gamma and poly(rI:rC) (pIC). In embryo fibroblasts
      derived from Pkr(o/o) mice, interferon regulatory factor 1 (IRF-1) or guanylate
      binding protein (Gbp) promoter-reporter constructs were unresponsive to IFN-gamma
      or pIC but response could be restored by co-transfection with PKR. The lack of
      responsiveness could be attributed to a diminished activation of IRF-1 and/or NF
      kappaB in response to IFN-gamma or pIC. Thus, PKR acts as a signal transducer for
      IFN-stimulated genes dependent on the transcription factors IRF-1 and NF-kappaB.

PMID- 9029160
TI  - Pop3p is essential for the activity of the RNase MRP and RNase P
      ribonucleoproteins in vivo.
AB  - RNase MRP is a ribonucleoprotein (RNP) particle which is involved in the
      processing of pre-rRNA at site A3 in internal transcribed spacer 1. Although
      RNase MRP has been analysed functionally, the structure and composition of the
      particle are not well characterized. A genetic screen for mutants which are
      synthetically lethal (sl) with a temperature-sensitive (ts) mutation in the RNA
      component of RNase MRP (rrp2-1) identified an essential gene, POP3, which encodes
      a basic protein of 22.6 kDa predicted molecular weight. Over-expression of Pop3p
      fully suppresses the ts growth phenotype of the rrp2-1 allele at 34 degrees C and
      gives partial suppression at 37 degrees C. Depletion of Pop3p in vivo results in
      a phenotype characteristic of the loss of RNase MRP activity; A3 cleavage is
      inhibited, leading to under-accumulation of the short form of the 5.8S rRNA
      (5.8S(S)) and formation of an aberrant 5.8S rRNA precursor which is 5'-extended
      to site A2. Pop3p depletion also inhibits pre-tRNA processing; tRNA primary
      transcripts accumulate, as well as spliced but 5'- and 3'-unprocessed pre-tRNAs.
      The Pop3p depletion phenotype resembles those previously described for mutations
      in components of RNase MRP and RNase P (rrp2-1, rpr1-1 and pop1-1).
      Immunoprecipitation of epitope-tagged Pop3p co-precipitates the RNA components of
      both RNase MRP and RNase P. Pop3p is, therefore, a common component of both RNPs
      and is required for their enzymatic functions in vivo. The ubiquitous RNase P
      RNP, which has a single protein component in Bacteria and Archaea, requires at
      least two protein subunits for its function in eukaryotic cells.

PMID- 9029161
TI  - DNA double-strand breaks caused by replication arrest.
AB  - We report here that DNA double-strand breaks (DSBs) form in Escherichia coli upon
      arrest of replication forks due to a defect in, or the inhibition of, replicative
      DNA helicases. The formation of DSBs was assessed by the appearance of linear DNA
      detected by pulse-field gel electrophoresis. Processing of DSBs by recombination
      repair or linear DNA degradation was abolished by mutations in recBCD genes. Two
      E. coli replicative helicases were tested, Rep, which is essential in recBC
      mutants, and DnaB. The proportion of linear DNA increased up to 50% upon shift of
      rep recBTS recCTS cells to restrictive temperature. No increase in linear DNA was
      observed in the absence of replicating chromosomes, indicating that the formation
      of DSBs in rep strains requires replication. Inhibition of the DnaB helicase
      either by a strong replication terminator or by a dnaBTS mutation led to the
      formation of linear DNA, showing that blocked replication forks are prone to DSB
      formation. In wild-type E. coli, linear DNA was detected in the absence of RecBC
      or of both RecA and RecD. This reveals the existence of a significant amount of
      spontaneous DSBs. We propose that some of them may also result from the
      impairment of replication fork progression.

PMID- 9029162
TI  - AcSDKP plasma concentrations in patients with solid tumours: comparison of two
      chemotherapeutic regimens.
AB  - The tetrapeptide AcSer-Asp-Lys-Pro (AcSDKP) is a physiological inhibitor of the
      proliferation of haematopoietic stem cells and progenitors. In Ara-C-treated
      mice, its plasmatic concentrations decrease while the CFU-S start cycling.
      Infusion of synthetic AcSDKP (Goralatide) at this time protects them from
      haematoxicity by blocking early cycling of CFU-S. Both in vitro and in vivo, this
      effect seems to be optimal in a narrow range of concentrations. Thus, a better
      knowledge of the kinetics of endogenous AcSDKP during cancer treatment could help
      to optimize the treatments with Goralatide. AcSDKP plasma levels have been
      measured by a specific EIA in 14 cancer patients during the two initial monthly 5
      day courses of chemotherapy with 5-FU alone administered either by continuous
      infusions (six patients) or by 1 h daily infusions (eight patients). AcSDKP
      concentrations did not vary significantly during the first and the second course.
      Together with our previous results in AML patients treated with high doses
      chemotherapy (Ara-C and Anthracyclin), our present data suggest that the
      variations of endogenous AcSDKP in patients are dependent of the type, doses and
      schedule of chemotherapy.

PMID- 9029163
TI  - p53 mutation and absence of mdm2 amplification and Ki-ras mutation in 4
      hydroxyamino quinoline 1-oxide induced transplantable osteosarcomas in rats.
AB  - Previously, we reported the establishment of two transplantable osteosarcomas,
      one induced by local application of a carcinogen, 4-hydroxyamino quinoline 1
      oxide(4-HAQO), and another which developed spontaneously in rats, and their
      subdivision into four lines with high and low metastatic potential to the lung.
      In the present study, mutations of p53 and Ki-ras genes were investigated by PCR
      and SSCP followed by direct sequencing, and the amplification of the mdm2 gene
      was assessed by Southern blot analysis. Mutations of p53 in exon 7 were detected
      in 4-HAQO-induced transplantable osteosarcomas, but not their spontaneous
      counterparts, irrespective of the metastatic potentials. Direct sequencing
      revealed a CGC to CAC transition with an amino acid change of Arg to His, at
      codon 246. Neither Ki-ras mutations nor mdm2 amplification were detected in any
      of the transplantable tumors. The results suggest that while p53 mutations
      occurred during osteosarcoma development by 4-HAQO without mdm2 amplification and
      Ki-ras mutation does not contribute to osteosarcoma development in rats.

PMID- 9029164
TI  - Mutagenic, carcinogenic and cocarcinogenic activity of cashewnut shell liquid.
AB  - The petroleum ether extract of cashewnut shell (Anacardium occidentale) was
      tested for its mutagenic, carcinogenic and cocarcinogenic potency. Mutagenicity
      tests using Salmonella typhimurium (Ame's test) Strains TA 1535, TA 100 and TA 98
      showed that cashewnut shell liquid is non-mutagenic up to a concentration of
      0.003% (in 0.1 ml DMSO) with and without metabolic activation (S 9 mixture).
      Carcinogenicity testing using murine (female Swiss albino mice) two stage skin
      tumourigenesis model revealed that cashewnut shell liquid has no tumour
      initiating potency at a concentration of 10% (in 0.2 ml acetone) while it may act
      as weak promoter (P < 0.05) at a concentration of 5% (in 0.2 ml acetone). Testing
      for cocarcinogenic potency of cashewnut shell liquid (2% and 5% in 0.2 ml
      acetone) demonstrated that it has no cocarcinogenic potency on mouse skin tumour
      model when applied along with 2 x 10(-6)% benzo(a)pyrene in acetone up to a
      period of 20 weeks.

PMID- 9029165
TI  - Combination of chemotherapy and recombinant interferon-alpha in advanced non
      small cell lung cancer.
AB  - Some studies have shown that the combination of chemotherapy and interferon in
      non-small cell lung cancer (NSCLC) and other solid tumors is feasible and
      possesses antitumor activity. Our study was aimed at verifying whether the
      addition of recombinant human interferon alpha (rh-IFN alpha) to combined
      chemotherapy would be able to increase the response rate and survival of patients
      with NSCLC. Thirty-eight patients with previously untreated advanced NSCLC were
      evaluated in this study. Median age of patients was 57 years; performance status
      according to ECOG 0 and 1, 37 pts (97%); stage IIIB, 27 pts (71%); stage IV, 11
      pts (29%). Histology was squamous cell carcinoma in 53%, adenocarcinoma 44% and
      large cell carcinoma 3%. Our schedule consisted of 80 mg/m2 cisplatin I.V., 100
      mg/m2 etoposide I.V., 10 million U rh-IFN alpha IM and 10 million U rh-IFN alpha
      I.V. on first day of treatment, every 3 weeks. None of the patients had complete
      response. Partial response rate was 34%. Median response duration was 7 months
      (range 3-19 months), median survival time was 11 months (range 4-41 months).
      Twenty-nine percent of patients had grade 3 nausea and vomiting, 24% had grade 2
      leucopenia, 5% had grade 2 cardiotoxicity, 2.6% had flu-like syndrome. According
      to these results, in advanced NSCLC, the addition of rh-IFN alpha did not
      increase the cisplatin-etoposide combined chemotherapy induced response rate and
      survival time.

PMID- 9029166
TI  - Lung resistance protein (LRP) expression in human normal tissues in comparison
      with that of MDR1 and MRP.
AB  - MDR1 (P-glycoprotein), multidrug resistance-associated protein (MRP) and lung
      resistance protein (LRP) are associated with multidrug resistance in various
      cancer cells. It is known that P-glycoprotein and MRP are also expressed in
      several normal tissues. However, the exact location of LRP in normal tissues is
      still unclear. In order to obtain more insight into the physiological role of
      LRP, its expression in human normal tissues was examined by an
      immunohistochemical technique, using one monoclonal antibody, LRP-56. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) was also utilized for several
      cell lines and fresh-frozen tissues. P-glycoprotein was found to be expressed in
      the kidney, adrenal, brain vessels, muscle, lung, pancreas, liver, intestine,
      placenta and testis. MRP was expressed in the kidney, adrenal, lung, pancreas,
      muscle, intestine, thyroid and prostate, and its distribution mostly overlapped
      with that of P-glycoprotein. Interestingly, MRP was not expressed in the liver.
      LRP at 110 kDa was expressed in the kidney, adrenal, heart, lung, muscle,
      thyroid, prostate, bone marrow and testis. These findings suggest that LRP as
      well as P-glycoprotein and MRP plays distinct roles in the physiology of various
      organs.

PMID- 9029167
TI  - Highly metastatic hepatocellular carcinomas induced in male F344 rats treated
      with N-nitrosomorpholine in combination with other hepatocarcinogens show a high
      incidence of p53 gene mutations along with altered mRNA expression of tumor
      related genes.
AB  - The carcinogenic and metastatic processes are thought to consist of a sequence of
      steps, and animal models featuring highly metastatic lesions are clearly
      necessary to allow analysis of the whole process of transformation from
      preneoplastic changes to high grade metastatic tumors, and to access
      effectiveness of therapeutic treatments of advanced cancers in vivo. The purpose
      of the present study was to establish a model and to screen for reported genetic
      alterations in induced lesions. In the present study, it was confirmed that lung
      metastasis of hepatocellular carcinomas (HCCs) induced in male F344 rats by N
      nitrosomorpholine (NNM), given in the drinking water at a dose of 120 ppm for 24
      weeks, was significantly enhanced by additional carcinogenic pretreatments and
      that a single i.p. injection of 100 mg/kg body weight N-diethylnitrosamine (DEN)
      alone was sufficient for that purpose. Molecular biological analyses of the
      induced lesions revealed point mutations in the p53 gene in 60.9% of HCCs, and
      elevated expression of mRNAs for p53, c-myc, c-fos, TGF-alpha, TGF-beta1, alpha
      fetoprotein, GST-P, and GGT, and decreased mRNA expression of EGF and EGFR in
      HCCs when compared to controls. No obvious association of gene alterations with
      metastatic potential of primary tumors was found except for an increase in the
      incidence of p53 mutations. Since the process of metastasis is thought to be
      sequential and selective, further comparative analysis of metastatic and primary
      lesions should clarify the mechanisms involved in the multi-step process of
      metastasis.

PMID- 9029169
TI  - Induction of lung carcinogenesis in AKR-mice by N
      nitrosodiethylamine/phenobarbitone, associated with high expression of c-myc and
      c-jun oncoproteins.
AB  - Lung carcinogenesis was induced in AKR mice using N-nitrosodiethylamine (NDEA).
      Tumors were detected in 46.8% of mice provided with 100 ppm NDEA in drinking
      water. The incidence of tumors was increased to 64.2% when the same
      carcinogenesis was promoted by phenobarbitone (PB). Lung tumor bearing mice
      showed no tumors in other organs. Characteristic features of these lung tumors
      are: (i) appearance of tumors within a short period of time i.e. less than 75
      days; (ii) no increase in the number and size of tumors with the increase in dose
      and duration of treatment of carcinogen; (iii) the same histological type was
      maintained in more than 80% of tumors. Animals that received treatment for 75-125
      days showed no significant advancement in the stage of carcinogenesis in
      comparison to the 50-75 days treatment period. Moreover, mice which received
      treatment for 125-150 days, did not have any neoplastic lesions in lungs, but
      they consisted of liver tumors generally. Expression of oncoproteins, c-myc and c
      jun, was detected in all lung tumors but the expression of c-myc protein was more
      than that of c-jun and both of these oncoproteins were enhanced by the promoter,
      PB. Highest level of expression of c-myc and c-jun was detected within the period
      of 50-75 days, whereafter it was decreased significantly within the period of 75
      125 days and 125-150 days of treatment. Thus, the results indicate that c-myc/c
      jun might be involved in the development of lung cancer in AKR mice, but may not
      have any role in the maintenance of the malignant phenotype of lungs.

PMID- 9029168
TI  - Alternative splicing of the erythropoietin receptor gene correlates with
      erythroid differentiation in rat hematopoietic and leukemic cells.
AB  - An alternative splicing of the rat erythropoietin receptor (EpoR) gene was
      identified in normal and erythroleukemia cells. A 105 bp insert was found at a
      region corresponding to the extracellular domain of EpoR. The alternative
      transcript was translated to a soluble EpoR (EpoR-S) expressed in spleen, bone
      marrow, and cultured erythroleukemia cells in addition to the full-length EpoR
      (EpoR-F). One of the rat erythroleukemia sublines, K4DT, which partially lost
      erythroid phenotypes and manifested monocyte/macrophage characteristics also
      lacked EpoR-S expression. Thus, expression of EpoR-S may play an important role
      in differentiation of rat erythroid cells.

PMID- 9029170
TI  - Selective hyperexpression of c-jun oncoprotein by glass fiber- and silica
      transformed BALB/c-3T3 cells.
AB  - Mining and mineral processing are important industries in the United States. A
      large number of workers are potentially exposed to silica during mining and to
      glass fibers during manufacturing. There is a concern regarding lung cancer risk
      among workers exposed to silica and glass fibers. Our previous studies showed
      that both glass fibers and silica induced transformation of BALB/c-3T3 cells. In
      order to explore the relationship between silica and glass fiber-induced cell
      transformation and oncoprotein expression, the protein products of seven proto
      oncogenes (c-K-ras, c-H-ras, c-sis, c-myc, c-myb, c-erb B1 and c-jun) and one
      tumor suppressor gene (p53) were examined in BALB/c-3T3 cells transformed by
      glass fibers or silica using immunoblotting with specific monoclonal or
      polyclonal antibodies. The results showed that all transformants, including eight
      induced by glass fibers and eight by silica (Min-U-Sil 5), were positive for c
      jun protein expression; the level of c-jun protein was elevated 8-21-fold in
      these transformants. Other protooncogene proteins in transformed cells were
      either not detectable or not different from non-transformed cells. These results
      suggest that the overexpression of c-jun is common in BALB/c-3T3 transformed
      cells induced by glass fibers or silica. It seems, therefore, that the expression
      of c-jun may play an important role in the transformation process.

PMID- 9029171
TI  - Polymorphism of metabolizing genes and lung cancer histology: prevalence of
      CYP2E1 in adenocarcinoma.
AB  - The relationship between genetic predisposition and development of specific
      cancers has not been adequately elucidated. In this study, the involvement of
      three polymorphic genes (CYP2E1, GSTM1, and GSTT1) in the development of
      different histological types of lung cancer was investigated. DNA was extracted
      from peripheral blood lymphocytes of lung cancer patients who have been long-term
      cigarette smokers (n = 52). Allelic variants of CYP2E1 were detected using PCR
      followed by PstI restriction enzyme digest and RFLP analysis, which detects a
      specific mutation causing over-expression of the gene. GSTM1 and GSTT1 genotypes
      were detected using two separate differential PCR methods. Our results indicate a
      13.5% allele frequency for the CYP2E1 rare PstI site among the lung cancer
      patients which represents a 3.4-fold increase over the normal controls (OR = 3.5,
      95% CL = 0.65-25.8). A novel observation is that all the patients with this
      polymorphism had adenocarcinomas only, resulting in a significant association
      between them (OR = 16.17, 95% CL = 0.95-73, P = 0.02). The frequency of the null
      GSTM1 gene was 42.3% among the lung cancer patients with no preferential tendency
      towards developing squamous cell carcinoma versus adenocarcinoma (OR = 1.10, 95%
      CL = 0.3-4.14, P = 0.5). The GSTT1 gene was absent in 21.1% of the patients with
      a non-significant tendency towards developing squamous cell carcinoma (OR = 1.23,
      95% CL = 0.25-6.1, P = 0.5). Another important observation is the significant
      predominance of the three predisposing polymorphic alleles among the
      adenocarcinoma patients (OR = 3.4, 95% CL = 0.78-16.1, P = 0.05) compared with
      the squamous cell carcinoma patients. The results of this study indicate that the
      inheritance of several polymorphic metabolizing genes, particularly the CYP2E1
      gene, contributes not only to the development of lung cancer but also to the
      development of specific types of cancer.

PMID- 9029172
TI  - Sonodynamically induced antitumor effect of gallium-porphyrin complex by focused
      ultrasound on experimental kidney tumor.
AB  - The antitumor effect of a gallium-porphyrin complex, ATX-70, induced by focused
      ultrasound, on colon 26 carcinoma implanted in a mouse kidney was investigated.
      Colon 26 tumors were exposed to focused ultrasound at 500 kHz and 1 MHz in a
      progressive wave mode. Both frequency components were superimposed onto each
      other in the focal zone to efficiently produce cavitation in the tumor. ATX-70
      was administered intravenously at the dose of 2.5 mg/kg, 24 h before the
      ultrasonic exposure. Antitumor effects were evaluated by histological observation
      7 days after the exposure. The destruction of tumor tissue was observed with the
      ultrasonic treatment in combination with ATX-70, while neither the treatment with
      ATX-70 alone nor that with ultrasound alone caused any necrosis. These results
      first demonstrated that antitumor effects of a porphyrin compound can be induced
      by focused ultrasound in a progressive wave mode.

PMID- 9029174
TI  - New protein and PCR markers RAK for diagnosis, prognosis and surgery guidance for
      breast cancer.
AB  - Breast cancer antigens RAK-p120, -p42, -p25 were detected in 100% of breast
      cancer cases tested (71 cases). Only 10% of adjacent tissue cases tested positive
      for all three cancer antigens, and 17.5% of the cases tested positive for two
      antigens only. Eighty-five percent of histologically normal breast tissue
      samples, isolated either from breast cancer patients or patients with advanced
      fibrocystic disease, tested RAK-negative, with the exception of low expression of
      p25, observed in some patients. Polymerase chain reaction (PCR) with HIV-1 gp 41
      derived primers revealed cancer-associated DNA fragments of similar size (140 bp)
      as in HIV-1 genome. Fifty-four percent of cancer adjacent tissues, and 50% of
      malignancy-free breast tissue samples, tested PCR-negative. It is suggested that
      genetic predisposition to cancer may be associated with the presence of RAK
      genes, while expression of RAK antigens marks an already ongoing process of
      malignant changes.

PMID- 9029173
TI  - Non-promoting effects of iron from beef in the rat colon carcinogenesis model.
AB  - Significant alarm has existed among the general public in the past few years that
      eating red meat may cause human colon cancer. Iron in beef has been hypothesized
      as one of the factors in the etiology of this cancer. The present study was
      designed to test the hypothesis that dietary iron solely from beef would enhance
      colon tumorigenesis induced in rats. Tumors were induced in Sprague-Dawley rats
      with 1,2-dimethylhydrazine (20 mg/kg body weight for 10 weeks). Seventy male
      weanling rats were randomized to two dietary treatment groups with two iron
      sources (very lean beef vs. iron citrate) as the factor. The rats were allowed
      free access to the respective diet and deionized water for 27 weeks. At
      termination of the study, the rats were examined for location, size and type of
      colon or extracolonic lesions. No significant differences were found in total
      incidence and number of colon tumors between the beef (51.7%, 0.8 tumors/rat) and
      casein (62.1%, 0.9 tumors/rat) diets, although the serum iron levels of rats fed
      the beef diet were higher than for those fed the casein diet. The results
      demonstrate that, when lean beef is used as an iron source, the risk for colon
      carcinogenesis is not increased.

PMID- 9029175
TI  - Stimulation of cell proliferation and inhibition of gap junctional intercellular
      communication by linoleic acid.
AB  - The effect of linoleic acid (LA) on gap-junction permeability, connexin 43 mRNA
      level, protein level, and phosphorylation, and the numbers of gap-junctional
      membrane plaques were studied in the rat liver epithelial cell line WB-F344 to
      determine whether changes in these parameters correlated with the enhanced cell
      growth and the inhibition of gap-junction function. When cultured in a medium
      with low serum (1%), these cells exhibited a slower growth rate than in the high
      serum medium (7%). Addition of linoleic acid (0.01-3 mg/ml) to the low serum
      medium increased the growth rate and inhibited gap junctional intercellular
      communication (GJIC) in a dose-dependent manner. In a comparison of short-term
      and long-term treatments with LA, GJIC in short-term treated (1 h) WB cells was
      inhibited at 3 mg/ml LA but readily recovered by washing and removing LA from
      cells, whereas GJIC in long-term treated (6 days) WB cells did not recover by
      washing and removing LA from WB cells. Western blot analysis of connexin 43
      showed that a short-term incubation with linoleic acid increased the relative
      amount of unphosphorylated connexin 43 protein, but a long-term incubation with
      linoleic acid decreased the amount of unphosphorylated connexin 43 protein and
      increased the relative amount of hyperphosphorylated connexin 43 protein.
      Connexin 43 and p53 mRNA levels decreased in a time- and dose-dependent manner in
      linoleic acid-treated cells. These results suggest that growth stimulation and
      gap junctional intercellular communication inhibition of rat liver epithelial
      cells by linoleic acid may be mediated in part through modulation of p53
      expression and function.

PMID- 9029178
TI  - Trials and tribulations.

PMID- 9029176
TI  - Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a
      highly oxygenated diterpene isolated from Tripterygium wilfordii.
AB  - Triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii
      Hook f. (Celastraceae), has been shown to demonstrate potent antileukemic
      activity in rodent models at remarkably low treatment doses. A variety of other
      physiological responses are known to be mediated by this compound, including
      immunosuppressive and antifertility effects. We currently report that triptolide
      was not mutagenic toward Salmonella typhimurium strain TM677, either in the
      presence or absence of a metabolic activating system. Relatively potent but non
      specific cytotoxicity was observed with a panel of cultured mammalian cell lines,
      and modest antitumor activity was observed when an i.p. dose of 25 microg was
      administered three times weekly to athymic mice carrying human breast tumors.
      Treatment regimens involving higher doses of triptolide (e.g. 50 microg/mouse
      three times weekly) were lethal.

PMID- 9029177
TI  - Mechanism of enhancement of esophageal tumorigenesis by 6-phenylhexyl
      isothiocyanate.
AB  - 6-Phenylhexyl isothiocyanate (PHITC) enhances esophageal tumorigenesis induced by
      the carcinogen N-nitrosomethylbenzylamine (NMBA) in rats while its shorter chain
      analog, phenethyl isothiocyanate (PEITC), inhibits NMBA-induced esophageal
      tumorigenesis. A significant increase in O6-methylguanine levels in esophageal
      DNA at 72 h after NMBA administration to rats pretreated with PHITC suggested
      that PHITC might enhance NMBA metabolic activation or inhibit DNA repair. To test
      this hypothesis, groups of 20 rats were administered PEITC or PHITC at
      concentrations of 0, 1.0, or 2.5 mmol/kg in modified AIN-76A diet for 2 weeks.
      The esophagi were removed from rats, stripped, split, and maintained in HEPES
      buffered saline (HBS) for assays of NMBA metabolism (n = 5 per group) or were
      snap frozen for DNA repair assays (n = 15 per group). The principal metabolites
      of NMBA produced by esophageal explants were: two unidentified peaks, benzyl
      alcohol (at 4 h only), and benzoic acid. Esophageal explants from PEITC-treated
      animals showed a significantly decreased ability to metabolize NMBA as expected.
      PHITC-treated animals showed a slight inhibition in the formation of most NMBA
      related metabolites, rather than an overall increase in NMBA activation. This
      inhibition was less than that observed with PEITC. No inhibitory effects were
      observed on O6-alkylguanine transferase (AGT) activity in the esophagi of rats
      treated with 1.0 micromol/g or 2.5 micromol/g PHITC. Thus, effects of PHITC on
      esophageal metabolism and DNA repair do not account for the enhancement of NMBA
      tumorigenicity by PHITC.

PMID- 9029179
TI  - Therapy of acute myelogenous leukemia: understanding the question, understanding
      the answer.
AB  - The best therapy for people with acute myelogenous leukemia (AML) in first
      remission is controversial. Options include postremission chemotherapy, a bone
      marrow transplant (HLA-identical sibling or autotransplant) or chemotherapy
      followed by a transplant at relapse. Four large cooperative group trials address
      this issue. In this review design and implementation of these trials is
      considered. Whether data from these trials will answer the questions of the best
      therapy for AML in first remission, is focused upon.

PMID- 9029180
TI  - Protection from apoptotic cell death by interleukin-4 is increased in previously
      treated chronic lymphocytic leukemia patients.
AB  - Chronic lymphocytic leukemia (CLL) cells were cultured in a medium supplemented
      with 0.01-1 ng/ml interleukin-4 (IL-4) for 18 h, fixed and analyzed on a flow
      cytometer. The percentage of apoptotic (AP) cells with hypodiploid DNA content
      was determined from DNA histograms. IL-4 at 0.01 ng/ml protected from spontaneous
      apoptosis of cells from previously treated CLL patients, but had very little
      effect on apoptotic death in cultures of cells from untreated patients. The
      number of AP cells in the absence of IL-4 was similar in cultures from treated
      and untreated patients. The concentration of IL-4 which inhibited spontaneous
      apoptosis by 50% was less than 0.01 ng/ml for pretreated patients and close to 1
      ng/ml for untreated patients. Stage of the disease had no effect on the level of
      spontaneous apoptosis and its sensitivity to IL-4. Protection from apoptosis by
      IL-4 was not accompanied by the upregulation of bcl-2 protein. The number of AP
      cells in methylprednisolone hemisuccinate (MP) treated cultures from previously
      treated patients was significantly lower than in cultures from untreated patients
      in the presence of 0.01-1.0 ng/ml IL-4. Treatment with the combination L
      phenylalanine mustard (L-PAM)+ fludarabine induced synergistic apoptotic
      response. Apoptosis induced by this combination was relatively resistant to IL-4
      in patients treated with chlorambucil and prednisone, but not in patients
      previously treated with fludarabine. Protection from cytotoxicity by IL-4 may be
      one of the mechanisms of acquired drug resistance in CLL.

PMID- 9029181
TI  - Interleukin-4 is a pleotropic cytokine with effects on B-cell malignancies.

PMID- 9029182
TI  - Predictors for optimal mobilization and subsequent engraftment of peripheral
      blood progenitor cells following intermediate dose cyclophosphamide and G-CSF.
AB  - Fifty consecutive patients undergoing cyclophosphamide/G-CSF mobilization were
      studied for indicators predictive for adequate harvest (CD34+ cells > 2 x
      10(6)/kg, CFU-GM > 1 x 10(5)/kg). Target yields following a single leukopheresis
      were achieved for 66% of patients (89% with no previous alkylation chemotherapy
      or radiotherapy). Previous alkylation therapy, radiotherapy and low collection
      day platelet count were predictive of poor collection yields. Following
      reinfusion, the median time to platelets > 20 x 10(9)/l (PLT > 20) was 10 days
      and to neutrophils > 500 x 10(6)/l (ANC > 500) was 13 days. Total CD34+ cells
      infused was predictive of early platelet engraftment. Previous radiotherapy was
      inversely predictive of neutrophil engraftment. For the majority of patients not
      exposed to alkylation therapy or radiotherapy, adequate progenitor cells can be
      collected following a single leukopheresis. In patients suitable for future
      autologous bone marrow transplantation it would seem appropriate to avoid or
      minimize radiotherapy and alkylation therapy exposure in the pre-collection
      period.

PMID- 9029183
TI  - Perturbation in the ability of bone marrow stroma from patients with acute
      myeloid leukemia but not chronic myeloid leukemia to support normal early
      hematopoietic progenitor cells.
AB  - The ability of bone marrow (BM) stroma derived from patients with acute myeloid
      leukemia (AML) or chronic myeloid leukemia (CML) to support normal hematopoiesis
      was investigated using a two-stage long-term bone marrow culture (LTBMC)
      procedure. Of particular interest was whether leukemia-derived stroma were
      capable of supporting the very immature, uncommitted hematopoietic progenitor
      cells (HPC) which are considered to have a higher dependence and association with
      the BM stroma than the more mature committed HPC. Confluent stromal layers were
      recharged with selected populations of normal HPC enriched for the CD34+CD38-
      cells (immature, uncommitted HPC) or the CD34+CD38+ cells (mature, committed
      HPC). The weekly output of clonable granulocyte-macrophage progenitor cells (CFU
      GM) was used as an indicator of the hematopoietic-supporting ability of the
      cultures. Stromal layers derived from 5/7 patients newly diagnosed with AML,
      showed significantly depressed ability to support the CD34+CD38- cells compared
      to stroma derived from normal donors. The supporting function of the AML-derived
      stroma for the more mature CD34+CD38+ cells was similar to that of the normal
      stroma (3/3 cases). Stromal layers derived from patients with chronic-phase CML
      showed normal or enhanced supporting function for the CD34+CD38- cells (5/6
      cases), and likewise for the CD34+CD38+ cells (3/3 cases). This study revealed a
      selective defect in the ability of BM stroma from patients with AML to support
      the maturation of normal early uncommitted HPC, represented by the CD34+CD38-
      cells, whilst the ability to support the committed CD34+CD38+ cells was not
      affected. This suggests that the BM microenvironment may be implicated in the
      disease mechanism of AML. It does not, however, appear to be as clearly
      implicated in chronic-phase CML.

PMID- 9029184
TI  - Ether lipids are effective cytotoxic drugs against multidrug-resistant acute
      leukemia cells and can act by the induction of apoptosis.
AB  - We studied the cytotoxic effects of two ether lipids, a relatively new class of
      anticancer drugs, on multidrug-resistant (MDR1) leukemia cells of patients with
      acute leukemias who had failed induction treatment. The cytotoxicity of ether
      lipids was determined by the elimination of clonogenic leukemia cells from
      leukemic cultures or, in case of failure to generate leukemic cultures, by the
      inhibition of 3[H]thymidine incorporation in leukemic blasts. At dose levels of
      50 microg/ml, a plasma level that can be achieved after oral intake, the MDR1
      positive blasts were killed, both of patients with drug-resistant acute myeloid
      leukemia (AML) and of patients with drug-resistant acute lymphoblastic leukemia
      (ALL). The leukemic blasts were killed by the induction of apoptosis. These data
      suggest that ether lipids may be effective antileukemic drugs and that their
      cytotoxic function is not affected by MDR1.

PMID- 9029185
TI  - Glucocorticoids induce apoptosis in acute myeloid leukemia cell lines with A
      t(8;21) chromosome translocation.
AB  - The t(8;21) chromosome translocation frequently occurs in the AML, acute myeloid
      leukemia, M2 sub-type. This translocation juxtaposes the AML1 gene on chromosome
      21 with the MTG8(ETO) gene on chromosome 8, resulting in the expression of the
      AML1-MTG8(ETO) fusion transcript. The fusion product is thought to play a
      critical role in the abnormal proliferation and differentiation of myeloid
      leukemia cells. We investigated the effects of various differentiation inducers
      of myeloid leukemia cells on the growth and differentiation of Kasumi-1 and SKNO
      1 cells, AML cell lines with t(8;21). These cells resisted differentiation into
      mature granulocytes and macrophages in response to various inducers of
      myelomonocytic differentiation, such as dimethyl sulfoxide, retinoic acid,
      butyrate, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1alpha,25
      dihydroxyvitamin D3. On the other hand, dexamethasone can induce apoptosis in
      these cells at low concentrations, whereas other myelomonocytic leukemia cell
      lines tested were resistant to glucocorticoid-induced apoptosis. The levels of
      glucocorticoid receptor gene expression were high in Kasumi-1 and SKNO-1 cells.
      Expression of the AML1-MTG8(ETO), bcl-2, and c-myc genes was unchanged following
      exposure to dexamethasone. Glucocorticoids might induce the apoptosis of some
      types of AML cells, just like that of some lymphoid leukemia cells.

PMID- 9029186
TI  - Suppression of in vitro maintenance of non-promyelocytic myeloid leukemia
      clonogenic cells by all-trans retinoic acid: modulating effects of dihydroxylated
      vitamin D3, alpha interferon and 'stem cell factor'.
AB  - In a liquid culture system, all-trans retinoic acid (ATRA), alone and in
      combination with dihydroxylated vitamin D3 (D3) or alpha interferon (alphaIFN) at
      concentrations achievable in vivo, could significantly suppress the maintenance
      of non-promyelocytic myeloid leukemia clonogenic cells (CFU-L) in 9/20, 9/18 and
      7/11 cases, respectively. That suppression was counteracted only slightly by the
      addition of 'stem cell factor', a cytokine which promotes CFU-L expansion in
      vitro. Differentiated cells slightly increased in 5/17 cases only, suggesting the
      prevalence of anti-proliferative rather than differentiating mechanisms. The
      present results extend our previous ones and suggest the possible therapeutical
      value of ATRA+D3 or alphaIFN, even in cases of non-promyelocytic myeloid
      leukemia.

PMID- 9029187
TI  - Chronic myeloid leukemic granulocytes exhibit reduced and altered binding to P
      selectin: modification in the CD15 antigens and sialylation.
AB  - Granulocytes from patients with chronic myeloid leukemia (CML) egress from the
      bone marrow before they are functionally mature and exhibit delayed emigration to
      sites of infection. To understand these defects, we have compared the binding of
      normal and CML granulocytes to the 293 cell line transfected with cDNA for P
      selectin. The CML granulocytes show significantly reduced binding to P-selectin
      relative to normal cells. The binding of normal granulocytes to P-selectin was
      significantly reduced when the cells were treated with anti CD15, polyclonal anti
      P-selectin, monoclonal anti-P-selectin (G1) antibodies or neuraminidase. On
      average, only 8% of the CML granulocyte population bound to P-selectin. The
      antibodies and neuraminidase were ineffective in inhibiting the binding of this
      population of leukemic cells. These data show that the morphologically mature CML
      granulocytes consist of a heterogeneous population of cells, some of which do not
      bind to P-selectin and others which adhere to the molecule via modified sugars.

PMID- 9029188
TI  - Expression of adhesion molecules in 113 patients with B-cell chronic lymphocytic
      leukemia: relationship with clinico-prognostic features.
AB  - The B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease, its
      clinical and biological behavior possibly being influenced by surface molecules
      expressed in B-lymphocytes. These molecules mediate cell adhesion, mobility and
      homing. Expression of surface adhesion molecules of the integrin family
      (CD11a/CD18 or LFA-1, CD11c/CD18), of the immunoglobulin-related family (CD54),
      of the selectin family (CD62L or LAM-1) and the lymphocyte homing receptor (CD44)
      were analyzed in peripheral cells from 113 B-CLL patients. The association with
      three prognosis-related parameters (Rai stage, bone marrow pattern and doubling
      time) was determined. The study included only patients with B-CLL lymphocytes of
      typical morphology, which always expressed CD5 and CD23. Low expression of
      integrins, particularly CD18, was associated with advanced disease (Rai stages
      III-IV) and diffuse bone marrow pattern, even after adjusting for other prognosis
      related variables. Expression of CD54 was associated independently with rapid
      doubling time (less than 12 months). The association persisted after adjusting
      for stage and bone marrow pattern; CD44 was expressed in all patients. No
      correlations were found between expression of CD62L and the prognostic variables
      analyzed. In conclusion, CD54 expression and low CD18 expression are both
      significantly associated with poor prognostic features.

PMID- 9029189
TI  - Interferon-alpha-2C and LD ara-C for the treatment of patients with CML: results
      of the Austrian multi-center phase II study.
AB  - Small pilot studies of patients with CML have reported on encouraging response
      rates after treatment with interferon-alpha (IFNalpha) in combination with low
      dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase
      II trial in order to investigate the efficacy and tolerability of this
      combination in newly diagnosed patients with Ph-positive chronic myelogenous
      leukemia (CML). Eighty-four patients were treated with IFN-alpha-2c at daily
      subcutaneous doses of 3.5 MU and LD ara-C added subcutaneously for 10 days every
      month at a dose of 10 mg/m2, following an initial reduction of WBC to less than
      20 x 10(9)/l with hydroxyurea (HU). Within a median observation period of 28 (5
      59) months the patients received a median of 7 (1-35) IFNalpha and LD ara-C
      cycles. Treatment was stopped due to side effects in 16 cases (19%) and to
      primary or secondary treatment failure in 38 cases (45%). In 45 patients (54%)
      complete hematological response (CHR) was achieved; in 39 patients (46%)
      cytogenetic responses including 15 (18%) complete cytogenetic responses (CHR)
      were observed. Median duration of cytogenetic responses was 15 months. Relapses
      were seen in 8/15 patients (53%) with complete cytogenetic remission (CCR), in
      3/6 patients (50%) with partial cytogenetic response and in 9/18 patients (50%)
      with minor cytogenetic response. In conclusion, the combination of IFNalpha and
      LD ara-C resulted in encouraging rates of hematological and cytogenetic responses
      in patients with CML with low to moderate toxicity.

PMID- 9029190
TI  - The combined differentiating effect of retinoic acid and vincristine on acute
      promyelocytic leukemia.
AB  - We have previously shown that HL-60 cells exposed to all-trans retinoic acid
      (ATRA) after treatment with a non-cytotoxic concentration of vincristine (VCR)
      result in granulocytic maturation and differentiation, suggesting that VCR might
      exhibit a synergistic action with ATRA in the treatment of acute promyelocytic
      leukemia. In this report, leukemic cells obtained from a patient with acute
      promyelocytic leukemia were exposed to 20 nM VCR for 1 h followed by 1 microM
      ATRA for 6 days. An increase in the expression of mature myelocyte antigens,
      CD11b and CD15, was observed as determined by flow cytometric analysis. Treatment
      of VCR or ATRA alone, however, did not have any effect on the expression of these
      mature myelocyte antigens of the leukemic cells. These results suggest that
      combined VCR and ATRA may be more efficient in the differentiation therapy of
      acute promyelocytic leukemia, particularly in those cases showing a slow response
      to ATRA therapy.

PMID- 9029191
TI  - Expand your differential.

PMID- 9029192
TI  - Airway and alveolar permeability and surface liquid thickness: theory.
AB  - The thickness of airway surface liquid (ASL) can be calculated as the ratio of
      the permeability coefficient of an absorbed inert tracer to the percentage rate
      in which it decreases in content in the airway lumen. The percentage clearance of
      radiolabeled diethylenetriaminepentaacetic acid (DTPA) from human airways or
      lungs has been measured many times, with a mean value of 1.04 +/- 0.25 (SD)
      %/min. Rates of clearance from animal lungs of most species give values of the
      same order, although they are lower in the sheep and higher in the dog.
      Permeability coefficients have not been measured simultaneously with percentage
      clearances and not at all for human tissues. Values for mannitol and sucrose, of
      which the former gives a permeability coefficient approximately 25% greater than
      that for sucrose and DTPA in airway tubes and isolated mucosal sheets from
      experimental animals, give a mean approximately 7.1 x 10(-7) cm/s. This
      corresponds to thickness of ASl of approximately 20-150 microns for various
      species. The assumptions underlying this estimate are discussed. It is concluded
      that ASL thickness in vivo may be considerably greater than in vitro measurements
      involving rapid freezing of the airway wall. Estimates of alveolar permeability
      suggest that either it is very considerably lower than that of the airway
      epithelium, that methods to measure alveolar permeability mainly reflect airway
      permeability, or both.

PMID- 9029193
TI  - Interaction of leg stiffness and surfaces stiffness during human hopping.
AB  - When mammals run, the overall musculoskeletal system behaves as a single linear
      "leg spring". We used force platform and kinematic measurements to determine
      whether leg spring stiffness (k(leg)) is adjusted to accommodate changes in
      surface stiffness (ksurf) when humans hoop in place, a good experimental model
      for examining adjustments to k(leg) in bouncing gaits. We found that k(leg) was
      greatly increased to accommodate surfaces of lower stiffnesses. The series
      combination of k(leg) and ksurf [total stiffness (ktot)] was independent of ksurf
      at a given hopping frequency. For example, when humans hopped at a frequency of 2
      Hz, they tripled their k(leg) on the least stiff surface (ksurf = 26.1 kN/m;
      k(leg) = 53.3 kN/m) compared with the most stiff surface (ksurf = 35,000 kN/m;
      k(leg) = 17.8 kN/m). Values for ktot were not significantly different on the
      least stiff surface (16.7 kN/m) and the most stiff surface (17.8 kN/m). Because
      of the k(leg) adjustment, many aspects of the hopping mechanics (e.g., ground
      contact time and center of mass vertical displacement) remained remarkably
      similar despite a > 1,000-fold change in ksurf. This study provides insight into
      how k(leg) adjustments can allow similar locomotion mechanics on the variety of
      terrains encountered by runners in the natural world.

PMID- 9029194
TI  - Nature and site of action of endogenous nitric oxide in vasculature of isolated
      pig lungs.
AB  - The site of action of endogenous and exogenous nitric oxide (NO) in isolated pig
      lungs was investigated by using arterial, double, and venous occlusions, which
      allowed precapillary, postcapillary, and venous segments to be partitioned into
      arterial, precapillary, postcapillary, and venous segments. NG-nitro-L-arginine
      (L-NNA; 10(-5) M) increased resistance in the arterial (35 +/- 6.6%. P = 0.003),
      precapillary (39.3 +/- 5.1%, P = 0.001), and venous (18.3 +/- 4.8%, P = 0.01)
      segments, respectively. Sodium nitroprusside (10(-5) M) NO (80 parts/million)
      reversed the effects of L-NNA. Total pulmonary vascular resistance fell with
      increasing flow, due to a fall in precapillary resistance and dynamic resistance,
      and was significantly lower than mean total resistance. L-NNA increased the
      resistances but did not alter the pattern of the pressure-flow relationships. It
      is concluded that, in isolated pig lungs, the effect of endogenous NO seems to be
      dependent on flow in the arterial segment and independent of flow in the
      precapillary segment, but variation of its release does not appear to be
      fundamental to accommodation to changes in steady flow.

PMID- 9029195
TI  - A distributed nonlinear model of lung tissue elasticity.
AB  - We present a theory relating the static stress-strain properties of lung tissue
      strips to the stress-bearing constituents, collagen and elastin. The fiber pair
      is modeled as a Hookean spring (elastin) in parallel with a nonlinear string
      element (collagen), which extends to a maximum stop length. Based on a series of
      fiber pairs, we develop both analytical and numerical models with distributed
      constituent properties that account for nonlinear tissue elasticity. The models
      were fit to measured stretched stress-strain curves of five uniaxially stretched
      tissue strips, each from a different dog lung. We found that the distributions of
      stop length and spring stiffness follow inverse power laws, and we hypothesize
      that this results from the complex fractal-like structure of the constituent
      fiber matrices in lung tissue. We applied the models to representative pressure
      volume (PV) curves from patients with normal, emphysematous, and fibrotic lungs.
      The PV curves were fit to the equation V = A--Bexp(-KP), where V is volume, P is
      transpulmonary pressure, and A, B, and K are constants. Our models lead to a
      possible mechanistic explanation of the shape factor K in terms of the structural
      organization of collagen and elastin fibers.

PMID- 9029196
TI  - Alignment of microvascular units along skeletal muscle fibers of hamster
      retractor.
AB  - When muscle fibers contract, blood flow requirements increase along their entire
      length. However, the organization of capillary perfusion along muscle fibers is
      unclear. The microvascular unit (MVU) is defined as a terminal arteriole and the
      group of capillaries it supplies. We investigated whether neighboring MVUs along
      the fiber axis perfused the same group of muscle fibers by using the parallel
      fibered retractor muscle. Hamsters were anesthetized and perfused with Microfil
      to visualize MVUs relative to muscle fibers. Fields of study, which encompassed
      five to seven neighboring MVUs along a muscle fiber, were chosen from the
      interior of muscles and along muscle edges. On average, MVUs were 1 mm in length,
      0.50 mm in width, and 0.1 mm deep; segments of approximately 30 fibers were
      contained in this tissue volume of 0.05 mm3 (20 MVUs/mg muscle). The total
      distance across muscle fibers encompassed by a pair of MVUs is designated "union"
      (U); the fraction of this distance common to both MVUs is designated
      "intersection" (I). The ratio of I to U for the widths of neighboring MVUs
      provides an index of MVU alignment along muscle fibers (e.g., I/U = 1.0 indicates
      complete alignment, where the fibers perfused by one MVU are the same as those
      perfused by the neighboring MVU). We found that I/U along muscle edges (0.71 +/-
      0.02) was greater (P < 0.05) than the ratio measured within muscles (0.66 +/-
      0.02). A model predicted a maximum I/U of 0.58 with random MVU alignment. Thus
      measured values were closer to random than to complete alignment. These findings
      indicate that an increase in blood flow along muscle fibers requires the
      perfusion of many MVUs and imply that vasodilation is coordinated among the
      parent arterioles from which corresponding MVUs arise.

PMID- 9029197
TI  - Testosterone and cortisol in relationship to dietary nutrients and resistance
      exercise.
AB  - Manipulation of resistance exercise variables (i.e., intensity, volume, and rest
      periods) affects the endocrine response to exercise; however, the influence of
      dietary nutrients on basal and exercise-induced concentrations of hormones is
      less understood. The present study examined the relationship between dietary
      nutrients and resting and exercise-induced blood concentrations of testosterone
      (T) and cortisol (C). Twelve men performed a bench press exercise protocol (5
      sets to failure using a 10-repetitions maximum load) and a jump squat protocol (5
      sets of 10 repetitions using 30% of each subject's 1-repetition maximum squat)
      with 2 min of rest between all sets. A blood sample was obtained at preexercise
      and 5 min postexercise for determination of serum T and C. Subjects also
      completed detailed dietary food records for a total of 17 days. There was a
      significant (P < or = 0.05) increase in postexercise T compared with preexercise
      values for both the bench press (7.4%) and jump squat (15.1%) protocols; however,
      C was not significantly different from preexercise concentrations. Significant
      correlations were observed between preexercise T and percent energy protein (r = 
      0.71), percent energy fat (r = 0.72), saturated fatty acids (g.1,000 kcal-1.day
      1; r = 0.77), monounsaturated fatty acids (g.1,000 kcal-1.day-1; r = 0.79, the
      polyunsaturated fat-to-saturated fat ratio (r = -0.63), and the protein-to
      carbohydrate ratio (r = -0.59). There were no significant correlations observed
      between any nutritional variables and preexercise C or the absolute increase in T
      and C after exercise. These data confirm that high-intensity resistance exercise
      results in elevated postexercise T concentrations. A more impressive finding was
      that dietary nutrients may be capable of modulating resting concentrations of T.

PMID- 9029198
TI  - Temporal dynamics of acute isovolume bronchoconstriction in the rat.
AB  - The time course of lung impedance changes after intravenous injection of
      bronchial agonist have produced significant insights into the mechanisms of
      bronchoconstriction in the dog (J. H. T. Bates, A.-M. Lauzon, G. S. Dechman, G.
      N. Maksym, and T. F. Shuessler. J. Appl. Physiol. 76: 616-626, 1994). We studied
      the time course of acute induced bronchoconstriction in five anesthetized
      paralyzed open-chest rats injected intravenously with a bolus of methacholine.
      For the 16 s immediately after injection, we held the lung volume constant while
      applying small-amplitude flow oscillations at 1.48, 5.45, and 19.69 Hz
      simultaneously, which provided us with continuous estimates of lung resistance
      (RL) and elastance (EL) at each frequency. This procedure was repeated at initial
      lung inflation pressures of 0.2, 0.4, and 0.6 kPa. Both RL and EL increased
      progressively after methacholine administration; however, the rate of change of
      EL increased dramatically as frequency was increased, whereas RL remained
      relatively independent of frequency. We interpret these findings in terms of a
      three-compartment model of the rat lung, featuring two parallel alveolar
      compartments feeding into a central airway compartment. Model simulations support
      the notions that both central airway shunting and regional ventilation
      inhomogeneity developed to a significant degree in our constricted rats. We also
      found that the rates of increase in both RL and EL were greatly enhanced as the
      initial lung inflation pressure was reduced, in accord with the notion that
      parenchymal tethering is an important mechanism limiting the extent to which
      airways can narrow when their smooth muscle is stimulated to contract.

PMID- 9029199
TI  - Muscle capillarization O2 diffusion distance, and VO2 kinetics in old and young
      individuals.
AB  - The relationships between muscle capillarization, estimated O2 diffusion distance
      from capillary to mitochondria, and O2 uptake (VO2) kinetics were studied in 11
      young (mean age, 25.9 yr) and 9 old (mean age, 66.0 yr) adults. VO2 kinetics were
      determined by calculating the time constants (tau) for the phase 2 VO2 adjustment
      to and recovery from the average of 12 repeats of a 6-min, moderate-intensity
      plantar flexion exercise. Muscle capillarization was determined from cross
      sections of biopsy material taken from lateral gastrocnemius. Young and old
      groups had similar VO2 kinetics (tau VO2-on = 44 vs. 48 s; tau VO2-off = 33 vs.
      44 s, for young and old, respectively), muscle capillarization, and estimated O2
      diffusion distances. Muscle capillarization, expressed as capillary density or
      average number of capillary contacts per fiber/average fiber area, and the
      estimates of diffusion distance were significantly correlated to VO2-off kinetics
      in the young (r = -0.68 to -0.83; P < 0.05). We conclude that 1) capillarization
      and VO2 kinetics during exercise of a muscle group accustomed to everyday
      activity (e.g., walking) are well maintained in old individuals, and 2) in the
      young, recovery of VO2 after exercise is faster, with a greater capillary supply
      over a given muscle fiber area or shorter O2 diffusion distances.

PMID- 9029200
TI  - Airway smooth muscle orientation in intraparenchymal airways.
AB  - Airway smooth muscle (ASM) shortening is the central event leading to
      bronchoconstriction. The degree to which airway narrowing occurs as a consequence
      of shortening is a function of both the mechanical properties of the airway wall
      as well as the orientation of the muscle fibers. Although the latter is
      theoretically important, it has not been systematically measured to date. The
      purpose of this study was to determine the angle of orientation of ASM (theta) in
      normal lungs by using a morphometric approach. We analyzed the airway tree of the
      left lower lobes of four cats and one human. All material was fixed with 10%
      buffered Formalin at a pressure of 25 cmH2O for 48 h. The fixed material was
      dissected along the airway tree to permit isolation of generations 4-18 in the
      cats and generations 5-22 in the human specimen. Each airway generation was
      individually embedded in paraffin. Five-micrometer-thick serial sections were cut
      parallel to the airway long axis and stained with hematoxylin-phloxine-saffron.
      Each block yielded three to five sections containing ASM. To determine theta, we
      measured the orientation of ASM nuclei relative to the transverse axis of the
      airway by using a digitizing tablet and a light microscope (x250) equipped with a
      drawing tube attachment. Inspection of the sections revealed extensive ASM
      crisscrossing without a homogeneous orientation. The theta was clustered between 
      20 degrees and 20 degrees in all airway generations and did not vary much between
      generations in any of the cats or in the human specimen. When theta was expressed
      without regard to sign, the mean values were 13.2 degrees in the cats and 13.1
      degrees in the human. This magnitude of obliquity is not likely to result in
      physiologically important changes in airway length during bronchoconstriction.

PMID- 9029201
TI  - Effects of a synthetic lung surfactant on pharyngeal patency in awake human
      subjects.
AB  - We examined the effects of separate applications of saline and a synthetic lung
      surfactant preparation (Surf; Exosurf Neonatal) into the supraglottic airway (SA)
      on the anteroposterior pharyngeal diameter (Dap) and the airway pressures
      required to close (Pcl) and reopen (Pop) the SA in five awake normal supine
      subjects. Dap, Pcl, and P(op) were determined during lateral X-ray fluoroscopy
      and voluntary glottic closure when pressure applied to the SA lumen was decreased
      from 0 to -20 cmH2O and then increased to +20 cmH2O. After Surf application and
      relative to control, Dap was larger for most of the applied pressures, Pcl
      decreased (-12.3 +/- 1.9 to -18.7 +/- 0.9 cmH2O; P < 0.01), P(op) decreased (13.4
      +/- 1.9 to -6.0 +/- 3.4 cmH2O; P < 0.01), and genioglossus electromyographic
      activity did not change (P > 0.05). Saline had no effect. These observations
      suggest that pharyngeal intraluminal surface properties are important in
      maintaining pharyngeal patency. We propose that surfactants enhance pharyngeal
      patency by reducing surface tension and adhesive forces acting on intraluminal SA
      surfaces.

PMID- 9029202
TI  - Myoglobin oxygen dissociation by multiwavelength spectroscopy.
AB  - Multiwavelength optical spectroscopy was used to determine the oxygen-binding
      characteristics for equine myoglobin. Oxygen-binding relationships as a function
      of oxygen tension were determined for temperatures of 10, 25, 35, 37, and 40
      degrees C, at pH 7.0. In addition, dissociation curves were determined at 37
      degrees C for pH 6.5, 7.0, and 7.5. Equilibration was achieved with a myoglobin
      solution, at the desired temperature and pH, and 16 oxygen-nitrogen gas mixtures
      of known oxygen fraction. Correction for the inevitable presence of metmyoglobin
      was made by using a three-component least squares analysis and by correcting the
      end point oxymyoglobin spectra for the presence of metmyoglobin. The PO2 at which
      myoglobin is half-saturated with O2 (P50) was determined to be 2.39 Torr at pH
      7.0 and 37 degrees C. The myoglobin dissociation curve was well fit by the Hill
      equation [saturation = PO2/(PO2 + P50)].

PMID- 9029203
TI  - Age-related changes in the twitch contractile properties of human thenar motor
      units.
AB  - The purpose of this study was to examine the effects of aging on the contractile
      and electrophysiological properties of human thenar motor units (MUs).
      Percutaneous electrical stimulation of single motor axons within the median nerve
      was used to isolate and examine the twitch tensions, contractile speeds, and
      surface-detected MU action potential (S-MUAP) sizes of 48 thenar MUs in 17
      younger subjects (25-53 yr) and 44 thenar MUs in 9 older subjects (64-77 yr). A
      wide range of twitch tensions, contractile speeds, and S-MUAP sizes was observed
      in both age groups. However, older subjects had significantly larger MU twitch
      tensions and slower MU twitch contraction and half-relaxation times. These
      changes were accompanied by increased S-MUAP sizes. These findings suggest that
      the human thenar MU pool undergoes significant age-related increase in MU size
      and slowing of contractile speed. Such adaptation may help to overcome previously
      reported age-related losses of thenar MUs.

PMID- 9029204
TI  - Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar
      hypoxia.
AB  - Arterial oxygen tensions (PaO2), atrial natriuretic peptide (ANP) concentrations,
      and circulating plasma volumes (PV) were measured in anesthetized rats ventilated
      with room air or 15, 10, or 8% O2 (n = 5-7). After 10 min of ventilation, PaO2
      values were 80 +/- 3, 46 +/- 1, 32 +/- 1, and 35 +/- 1 Torr and plasma
      immunoreactive ANP (irANP) levels were 211 +/- 29, 229 +/- 28, 911 +/- 205, and
      4,374 +/- 961 pg/ml, respectively. At PaO2 < or = 40 Torr, irANP responses were
      more closely related to inspired O2 (P = 0.014) than to PaO2 (P = 0.168). PV was
      36.3 +/- 0.5 microliters/g in controls but 8.5 and 9.9% lower (P < or = 0.05) for
      10 and 8% O2, respectively. Proportional increases in hematocrit were observed in
      animals with reduced PV; however, plasma protein concentrations were not
      different from control. Between 10 and 50 min of hypoxia, small increases (+40%)
      in irANP occurred in 15% O2; however, there was no further change in PV,
      hematocrit, plasma protein, or irANP levels in the lower O2 groups. Urine output
      tended to fall during hypoxia but was not significantly different among groups.
      These findings are compatible with a role for ANP in mediating PV contraction
      during acute alveolar hypoxia.

PMID- 9029205
TI  - Acute alveolar hypoxia increases blood-to-tissue albumin transport: role of
      atrial natriuretic peptide.
AB  - Plasma immunoreactive atrial natriuretic peptide (irANP) and blood-to-tissue
      clearance of 131I-labeled rat serum albumin (CRSA) were examined in anesthetized
      rats during hypoxic ventilation (n = 5-7/group). Hypoxia (10 min) increased irANP
      from 211 +/- 29 (room air) to 229 +/- 28 (15% O2, not significant), 911 +/- 205
      (10% O2), and 4,374 +/- 961 pg/ml (8% O2), respectively. Graded increases in CRSA
      were significant at 8% O2 in fat (3.6-fold), ileum (2.2-fold), abdominal muscles
      (2.0-fold), kidney (1.8-fold), and jejunum (1.4-fold). CRSA was decreased in back
      skin and testes; heart, brain, and lungs were unaffected. The increases in CRSA
      were related to irANP and not to arterial PO2. Circulating plasma volume was
      negatively correlated with whole body CRSA. Graded increases in extravascular
      water content (EVW) were found in the kidney, left heart, and cerebrum and were
      positively related to CRSA in the kidney. EVW decreased in gastrointestinal
      tissues; the magnitude was inversely related to CRSA. We conclude that ANP
      induced protein extravasation contributes to plasma volume contraction during
      acute hypoxia.

PMID- 9029206
TI  - Effects of carotid body hypocapnia during ventilatory acclimatization to hypoxia.
AB  - Hypoxic ventilatory sensitivity is increased during ventilatory acclimatization
      to hypoxia (VAH) in awake goats, resulting in a time-dependent increase in
      expired ventilation (VE). The objectives of this study were to determine whether
      the increased carotid body (CB) hypoxic sensitivity is dependent on the level of
      CB CO2 and whether the CB CO2 gain is changed during VAH. Studies were carried
      out in adult goats with CB blood gases controlled by an extracorporeal circuit
      while systemic (central nervous system) blood gases were regulated independently
      by the level of inhaled gases. Acute VE responses to CB hypoxia (CB PO2 40 Torr)
      and CB hypercapnia (CB PCO2 50 and 60 Torr) were measured while systemic normoxia
      and isocapnia were maintained. CB PO2 was then lowered to 40 Torr for 4 h while
      the systemic blood gases were kept normoxic and normocapnic. During the 4-h CB
      hypoxia, VE increased in a time-dependent manner. Thirty minutes after return to
      normoxia, the ventilatory response to CB hypoxia was significantly increased
      compared with the initial response. The slope of the CB CO2 response was also
      elevated after VAH. An additional group of goats (n = 7) was studied with a
      similar protocol, except that CB PCO2 was lowered throughout the 4-h CB hypoxic
      exposure to prevent reflex hyperventilation. CB PCO2 was progressively lowered
      throughout the 4-h CB hypoxic period to maintain VE at the control level. After
      the 4-h CB hypoxic exposure, the ventilatory response to hypoxia was also
      significantly elevated. However, the slope of the CB CO2 response was not
      elevated after the 4-h hypoxic exposure. These results suggest that CB
      sensitivity to both O2 and CO2 is increased after 4 h of CB hypoxia with systemic
      isocapnia. The increase in CB hypoxic sensitivity is not dependent on the level
      of CB CO2 maintained during the 4-h hypoxic period.

PMID- 9029207
TI  - Gender-specific effects of dexamethasone treatment on rat diaphragm structure and
      function.
AB  - The effects of long-term dexamethasone treatment on diaphragm muscle were studied
      in female and male rats. Compared with pair-fed control animals, dexamethasone
      treatment did not significantly affect estrous cycling or peak serum estradiol
      levels; however, testosterone levels were significantly increased in females and
      decreased in males. Dexamethasone significantly reduced body and costal diaphragm
      weights, but to a lesser extent in females than in males. Reductions in diaphragm
      weight were proportional to reductions in body weight. In females and males,
      dexamethasone treatment significantly decreased diaphragm fiber (types I and II)
      cross-sectional area and the relative expression of myosin heavy chain isoform
      2B. With the exception of type I fiber atrophy, these changes occurred to a
      lesser extent in females. Dexamethasone did not significantly affect specific
      forces. Dexamethasone significantly increased twitch one-half relaxation time and
      fatigue resistance indexes in males but not in females. In conclusion, the
      effects of long-term dexamethasone treatment were gender specific, with
      significantly fewer effects in females, and changes in serum testosterone levels
      were associated with these findings.

PMID- 9029208
TI  - Short- and long-term effects of testosterone on diaphragm in castrated and normal
      male rats.
AB  - The effects of short- and long-term testosterone absence or treatment on the
      diaphragm were studied in castrated and sexually normal male rats. Compared with
      control rats (untreated normal males), testosterone absence or treatment did not
      significantly affect costal weight. In untreated castrated males, there were
      significant decreases in specific forces, type II fiber cross-sectional area, and
      myosin heavy chain (MHC) isoform 2B after 2.5 wk. In castrated males that
      received testosterone, there were significant increases in specific forces, type
      II total fiber proportional area, and relative expression of all adult diaphragm
      fast MHC isoforms (MHC-2all) after 2.5 wk. In normal males that received
      testosterone, the only significant finding was an increase in MHC-2B after 2.5
      wk. Across all groups, there was close correlation between increases in maximum
      tetanic forces and MHC-2all. Changes in diaphragm function and composition were
      closely related to changes in serum testosterone levels at 2.5 wk. The lack of
      significant change in diaphragm function at 10 wk occurred despite changes in
      serum testosterone levels and diaphragm composition similar to those at 2.5 wk.
      These findings support our hypothesis that the effects of testosterone are
      dependent on basal circulating androgen levels and study duration.

PMID- 9029209
TI  - Effects of muscle kinematics on surface EMG amplitude and frequency during
      fatiguing dynamic contractions.
AB  - Fifteen male subjects performed a repetitive elbow flexion/extension task with a
      7-kg mass until exhaustion. Average joint angle, angular velocity, and biceps
      brachii surface electromyographic (EMG) amplitude (aEMG) and mean power frequency
      (MPF) were calculated with each consecutive 250-ms segment of data during the
      entire trial. Data were separated into concentric or eccentric phases and into
      seven 20 degree-ranges from 0 to 140 degrees of elbow flexion. A regression
      analysis was used to estimate the rested and fatigued aEMG and MPF values. aEMG
      values were expressed as a percentage of amplitudes from maximum voluntary
      contractions (MVC). Under rested dynamic conditions, the average concentric aEMG
      amplitude was 10% MVC higher than average eccentric values. Rested MPF values
      were similar for concentric and eccentric phases, although values increased
      approximately 20 Hz from the most extended to flexed joint angles. Fatigue
      resulted in an average increase in concentric and eccentric aEMG of 35 and 10%
      MVC, respectively. The largest concentric aEMG increases (up to 58% MVC) were
      observed at higher joint velocities, whereas eccentric increases appeared to be
      related to decreases in velocity. Fatigue had a similar effect on MPF during both
      concentric and eccentric phases. Larger MPF decreases were observed at shorter
      muscle lengths such that values within each angle range were very similar by the
      end of the trial. It was hypothesized that this finding may reflect a biological
      minimum in conduction velocity before propagation failure occurs.

PMID- 9029210
TI  - Air entry in infant resuscitation: oral or nasal routes?
AB  - The current recommendation for resuscitation of infants is to blow air into both
      the nose and mouth. We have observed that mothers cannot cover both the nose and
      mouth of their infants. We compared postmortem tracheal and esophageal air entry
      by using the nose, combined nose and mouth, and mouth routes in eight infants.
      Air entry into the trachea occurred at lower pressures (P < 0.05) via a nose mask
      than via a combined nose and mouth mask or via a mouth mask. Air entry into the
      trachea occurred at lower pressures (P < 0.05) via the nose route in the neutral
      and extended neck positions compared with the flexed position. We were unable to
      demonstrate an effect of the route of air entry on esophageal air entry. The
      findings indicate that the nasal route of air entry is more effective than the
      combined nose and mouth or mouth routes and that neck flexion impedes air entry.
      We recommend that parents are taught to blow air into their infants' noses if the
      infant stops breathing.

PMID- 9029211
TI  - Relationship between maximum aerobic power and resting metabolic rate in young
      adult women.
AB  - The literature is inconclusive as to the chronic effect of aerobic exercise on
      resting metabolic rate (RMR), and furthermore there is a scarcity of data on
      young women. Thirty-four young women exhibiting a wide range of aerobic fitness
      [maximum aerobic power (VO2max) = 32.3-64.8 ml.kg-1.min-1] were accordingly
      measured for RMR by the Douglas bag method, treadmill VO2max, and fat-free mass
      (FFM) by using Siri's three-compartment model. The interclass correlation (n =
      34) between RMR (kJ/h) and VO2max (ml.kg-1.min-1) was significant (r = 0.39, P <
      0.05). However, this relationship lost statistical significance when RMR was
      indexed to FFM and when partial correlation analysis was used to control for FFM
      differences. Furthermore, multiple linear-regression analysis indicated that only
      FFM emerged as a significant predictor of RMR (kJ/h). When high- (n = 12) and low
      fitness (n = 12) groups were extracted from the cohort on the basis of VO2max
      scores, independent t-tests revealed significant between-group differences (P <
      0.05) for RMR (kJ.kg-1.h-1) and VO2max (ml.kg-1.min-1) but not for RMR (kJ/h),
      RMR (kJ.kg FFM-1.h-1), and FFM. Analysis of covariance of RMR (kJ/h) with FFM as
      the covariate also showed no significant difference (P = 0.56) between high- and
      low-fitness groups. Thus the results suggest that 1) FFM accounts for most of the
      differences in RMR between subjects of varying VO2max values and 2) the RMR per
      unit of FFM in young healthy women is unrelated to VO2max.

PMID- 9029212
TI  - Diaphragm disuse reduces Ca2+ uptake capacity of sarcoplasmic reticulum.
AB  - Chronic phrenic tetrodotoxin (TTX) blockade and phrenic denervation (Dnv) of
      hamster diaphragm result in decreased maximum specific tension, prolonged
      contraction time, and improved fatigue resistance (W. Z. Zhan and G. C. Sieck, J.
      Appl. Physiol. 72: 1445-1453, 1992). An underlying increased relative
      contribution of type I fibers to total muscle mass appears to be consistent with,
      but does not completely account for, changes in contractile and fatigue
      properties. The present study was designed to evaluate a potential role for
      altered cellular Ca2+ metabolism in the adaptive response of the diaphragm to
      chronic disuse. An analytic method based on simulation and modeling of long-term
      45Ca2+ efflux data was used to estimate Ca2+ contents (nmol Ca2+/g wet wt tissue)
      and exchange fluxes (nmol Ca2+.min-1.g-1) for extracellular and intracellular
      compartments in the in vitro hamster hemidiaphragm after prolonged disuse. Three
      groups were compared: control (Con, n = 5), phrenic TTX blockade (TTX, n = 5),
      and phrenic denervation (Dnv, n = 5). Experimental muscles were loaded with
      45Ca2+ for 1 h, and efflux data were collected for 8 h by using a flow-through
      tissue chamber. Compartmental analysis of efflux data estimated that the Ca2+
      contents and Ca2+ exchange fluxes of the largest and slowest intracellular
      compartment (putative longitudinal reticulum) were reduced by approximately 50%
      in TTX and Dnv muscle groups compared with Con. In addition, the kinetic model
      predicted significant decreases in total intracellular Ca2+ and total diaphragm
      Ca2+ in TTX and Dnv muscles. We conclude that the data support the hypothesis
      that the capacity of the sarcoplasmic reticulum for Ca2+ sequestration is reduced
      in chronic diaphragm disuse. The impact of this effect on diaphragm contractile
      and fatigue properties is discussed.

PMID- 9029213
TI  - Respiratory transfer impedance between 8 and 384 Hz in guinea pigs before and
      after bronchial challenge.
AB  - We report a forced oscillatory technique for noninvasively measuring respiratory
      transfer impedance (Ztr) between 8 and 384 Hz in guinea pigs. This technique uses
      a device consisting of two chambers: one surrounding the animal's head that is
      used as a plethysmograph to measured flow through the airway opening and the
      other that surrounds the animal's body and is used to apply pressure oscillations
      to the body surface. Ztr was measured in spontaneously breathing awake guinea
      pigs and while the animals were anesthetized in normal and methacholine
      challenged conditions. An eight-element model consisting of an airway compartment
      separated from a tissue compartment by a shunt gas compression compartment was
      fit to the data. Anesthesia increased central and peripheral airway resistance
      and bronchial airway wall compliance by 13, 31, and 44%, respectively, whereas it
      decreased tissue compliance by 37%. Compared with the unanesthetized condition,
      the methacholine challenge (20 micrograms/kg) resulted in an increase in central
      and peripheral airway resistance (69 and 319%, respectively) and a decrease in
      bronchial airway wall and tissue compliance (37 and 79%, respectively). This
      technique is capable of measuring Ztr in anesthetized and awake guinea pigs.
      Analysis of these data with this eight-element model provides reasonable
      estimates of airway and tissue parameters.

PMID- 9029214
TI  - Lower limb skeletal muscle function after 6 wk of bed rest.
AB  - Force, electromyographic (EMG) activity, muscle mass, and fiber characteristics
      were studied in seven healthy men before and after 6 wk of bed rest. Maximum
      voluntary isometric and concentric knee extensor torque decreased (P < 0.05)
      uniformly across angular velocities by 25-30% after bed rest. Maximum quadricep
      rectified EMG decreased by 19 +/- 23%, whereas submaximum (100-Nm isometric
      action) EMG increased by 44 +/- 28%. Knee extensor muscle cross-sectional area
      (CSA), assessed by using magnetic resonance imaging, decreased by 14 +/- 4%.
      Maximum torque per knee extensor CSA decreased by 13 +/- 9%. Vastus lateralis
      fiber CSA decreased 18 +/- 14%. Neither type I, IIA, and IIB fiber percentages
      nor their relative proportions of myosin heavy chain (MHC) isoforms were altered
      after bed rest. Because the decline in strength could not be entirely accounted
      for by using decreased muscle CSA, it is suggested that the strength loss is also
      due to factors resulting in decreased neural input to muscle and/or reduced
      specific tension of muscle, as evidenced by decreased torque/EMG ratio.
      Additionally, it is concluded that muscle unloading in humans does not induce
      important changes in fiber type or MHC composition or in vivo muscle contractile
      properties.

PMID- 9029216
TI  - Source of error on A-aDO2 calculated from blood stored in plastic and glass
      syringes.
AB  - We studied the effects of time delay on blood gases, pH, and base excess in blood
      stored in glass and plastic syringes on ice and the effects of resulting errors
      on calculated alveolar-to-arterial PO2 difference (A-aDO2). Matched samples of
      dog whole blood were tonometered with gas mixtures of 5% CO2-12% )2-83% N2
      (mixture A), 10% CO2-5% O2-85% N2 (mixture B), and 2.88% CO2-4% O2-93.12% N2
      (mixture C). Tonometered blood samples were transferred to 5-ml glass (5G), 5-ml
      plastic (5P), and 3-ml plastic (3P) syringes and stored on ice. Blood gases were
      measured every 1 h up to 6 h. In 5G, PO2 progressively decreased in blood
      tonometered with mixture A but rose in blood tonometered with mixtures B and C.
      O2 saturation progressively fell in all cases. In 5G, blood PCO2 progressively
      rose regardless of which gas mixture was used, and pH as well as base excess
      progressively fell. The rise in PO2 was faster in plastic than in glass syringes,
      and O2 saturation always rose in plastic syringes. Differences between storage in
      plastic and glass syringes on PO2 change were greatest when initial blood PO2 was
      highest (mixture A). At the highest PO2, O2 exchange was faster in 3P than in 5P.
      The rise of PCo2 was just as fast in plastic as in glass syringes, but in both
      the rise in PCO2 was faster at a higher initial PCO2 (mixture B) than in lower
      initial PCO2 (mixtures B and C). Rates of PO2 and PCO2 change in matched samples
      were significantly faster in 3P than in 5P. Errors due to rises in PCO2 and PO2
      cause additive errors in calculated A-aDO2, and when blood is stored in plastic
      syringes for > 1 h significant errors result. Errors are greater in normoxic
      blood, in which estimated A-aDO2 decreased by > 10 Torr after 6 h on ice in
      plastic syringes, than in hypoxic blood.

PMID- 9029215
TI  - Peak force and maximal shortening velocity of soleus fibers after non-weight
      bearing and resistance exercise.
AB  - This study examined the effectiveness of resistance exercise as a countermeasure
      to non-weight-bearing-induced alterations in the absolute peak force, normalized
      peak force (force/fiber cross-sectional area), peak stiffness, and maximal
      shortening velocity (Vo) of single permeabilized type I soleus muscle fibers.
      Adult rats were subjected to the following treatments: normal weight bearing
      (WB), non-weight bearing (NWB), or NWB with exercise treatments (NWB+Ex). The
      hindlimbs of the NWB and NWB+Ex rats were suspended for 14 days via tail
      harnesses. Four times each day, the NWB+Ex rats were removed from suspension and
      performed 10 climbs (approximately 15 cm each) up a steep grid with a 500-g mass
      (approximately 1.5 times body mass) attached to their tail harness. NWB was
      associated with significant reductions in type I fiber diameter, absolute force,
      normalized force, and stiffness. Exercise treatments during NWB attenuated the
      decline in fiber diameter and absolute force by almost 60% while maintaining
      normalized force and stiffness at WB levels. Type I fiber Vo increased by 33%
      with NWB and remained at this elevated level despite the exercise treatments. We
      conclude that in comparison to intermittent weight bearing only (J.J. Widrick,
      J.J. Bangart, M. Karhanek, and R.H. Fitts. J. Appl. Physiol. 80: 981-987, 1996),
      resistance exercise was more effective in attenuating alterations in type I
      soleus fiber absolute force, normalized force, and stiffness but was less
      effective in restoring type I fiber Vo to WB levels.

PMID- 9029217
TI  - Comparison of techniques for measuring pulse-wave velocity in the rat.
AB  - We evaluated methods for measuring average and regional pulse-wave velocity along
      the full length of the aorta in 18-mo-old ether-anesthetized male spontaneously
      hypertensive rats. Catheter-tip manometers were placed in the ascending and
      descending thoracic aorta via the right carotid and left femoral arteries,
      respectively. As the distal catheter was withdrawn at 1-cm intervals, the
      relationship between the distal catheter insertion distance and distance between
      transducers was determined from the intercept of the insertion distance vs.
      transmission delay regression line. Methods that assessed the foot-to-foot time
      delay between pressures accurately predicted the separation between catheters
      (measured distance of 1.43 cm; intercept of 1.40 +/- 0.5 cm; P = not significant)
      were highly reproducible (coefficient of variation of 2.3% for repeated
      measurements) and showed minimal variability (range 509 +/- 30 to 600 +/- 29
      cm/s) along the full length of the aorta. Methods that made use of the pressure
      pressure transfer function were spatially (range of values along the aorta 367 +/
      17 to 722 +/- 39 cm/s) and temporally more variable, especially during
      vasoconstriction with methoxamine, due to the effects of reflected waves.

PMID- 9029218
TI  - Modulation of myosin isoform expression by mechanical loading: role of
      stimulation frequency.
AB  - This study tested for the hypothesis that mechanical loading, not stimulation
      frequency per se, plays a key role in determining the plasticity of myosin heavy
      chain (MHC) protein isoform expression in muscle undergoing resistance training.
      Female Sprague-Dawley rats were randomly assigned to resistance-training programs
      that employed active 1) shortening (n = 7) or 2) lengthening contractions (n =
      8). The medial gastrocnemius (MG) muscles in each group trained under loading
      conditions that approximated 90-95% of maximum isometric tetanic tension but were
      stimulated at frequencies of 100 and approximately 25 Hz, respectively.
      Lengthening and shortening contractions were produced by using a Cambridge
      ergometer system. The MG muscles trained every other day, performing a total of
      16 training session. Both training programs produced significant (P < 0.01) and
      similar reductions in the fast type IIB MHC protein isoform in the white MG
      muscle, reducing its relative content to approximately 50% of the total MHC
      protein isoform pool. These changes were accompanied by increases in the relative
      content of the fast type IIX MHC protein isoform that were of similar magnitude
      for both groups. The results of this study clearly demonstrate that stimulation
      frequency does not play a key role in modulating MHC isoform alterations that
      result from high-resistance training.

PMID- 9029219
TI  - Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein
      kinase and protein kinase A.
AB  - This study was designed to compare functional effects of phosphorylation of
      muscle acetyl-CoA carboxylase (ACC) by adenosine 3',5'-cyclic monophosphate
      dependent protein kinase (PKA) and by AMP-activated protein kinase (AMPK). Muscle
      ACC (272 kDa) was phosphorylated and then subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis followed by autoradiography. Functional
      effects of phosphorylation were determined by measuring ACC activity at different
      concentrations of each of the substrates and of citrate, an activator of the
      enzyme. The maximal velocity (Vmax) and the Michaelis constants (Km) for ATP,
      acetyl-CoA, and bicarbonate were unaffected by phosphorylation by PKA.
      Phosphorylation by AMPK increased the Km for ATP and acetyl-CoA. Sequential
      phosphorylation by PKA and AMPK, first without label and second with label,
      appeared to reduce the extent of label incorporation, regardless of the order.
      The activation constant (Ka) for citrate activation was increased to the same
      extent by AMPK phosphorylation, regardless of previous or subsequent
      phosphorylation by PKA. Thus muscle ACC can be phosphorylated by PKA but with no
      apparent functional effects on the enzyme. AMPK appears to be the more important
      regulator of muscle ACC.

PMID- 9029220
TI  - Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats
      given IL-1 intratracheally.
AB  - Interleukin-1 (IL-1) is increased in lung lavages from patients with the acute
      respiratory distress syndrome, and administering IL-1 intratracheally causes
      neutrophil accumulation and a neutrophil-dependent oxidative leak in lungs of
      rats. In the present study, we found that rats pretreated intraperitoneally with
      lisofylline [(R)-1-(5-hydroxyhexyl)-3, 7-dimethylxanthine (LSF)], an inhibitor of
      lysophosphatidic acid acyl transferase, which reduces the production of
      unsaturated phosphatidic acid species, did not develop the lung leak or the
      related ultrastructural abnormalities that occur after intratracheal
      administration of IL-1. However, rats pretreated with LSF and then given IL-1
      intratracheally did develop the same elevations of lung lavage cytokine-induced
      neutrophil chemoattractant (CINC) levels and the same increased numbers of lung
      lavage neutrophils as rats given IL-1 intratracheally. Lungs of rats given IL-1
      intratracheally also had increased unsaturated phosphatidic acid and free acyl
      (linoleate, linolenate) concentrations compared with untreated rats, and these
      lipid responses were prevented by pretreatment of LSF. Our results reveal that
      LSF decreases lung leak and lung lipid alterations without decreasing neutrophil
      accumulation or lung lavage CINC increases in rats given IL-1 intratracheally.

PMID- 9029221
TI  - Effects of surface tension and intraluminal fluid on mechanics of small airways.
AB  - Airway constriction is accompanied by folding of the mucosa to form ridges that
      run axially along the inner surface of the airways. The mucosa has been modeled
      (R. K. Lambert. J. Appl. Physiol. 71:666-673, 1991) as a thin elastic layer with
      a finite bending stiffness, and the contribution of its bending stiffness to
      airway elastance has been computed. In this study, we extend that work by
      including surface tension and intraluminal fluid in the model. With surface
      tension, the pressure on the inner surface of the elastic mucosa is modified by
      the pressure difference across the air-liquid interface. As folds form in the
      mucosa, intraluminal fluid collects in pools in the depressions formed by the
      folds, and the curvature of the air-liquid interface becomes nonuniform. If the
      amount of intraluminal fluid is small, < 2% of luminal volume, the pools of
      intraluminal fluid are small, the air-liquid interface nearly coincides with the
      surface of the mucosa, and the area of the air-liquid interface remains constant
      as airway cross-sectional area decreases. In that case, surface energy is
      independent of airway area, and surface tension has no effect on airway
      mechanics. If the amount of intraluminal fluid is > 2%, the area of the air
      liquid interface decreases as airway cross-sectional area decreases. and surface
      tension contributes to airway compression. The model predicts that surface
      tension plus intraluminal fluid can cause an instability in the area-pressure
      curve of small airways. This instability provides a mechanism for abrupt airway
      closure and abrupt reopening at a higher opening pressure.

PMID- 9029222
TI  - Effects of acute hyperoxic exposure on solute fluxes across the blood-gas barrier
      in rat lungs.
AB  - We investigated effects of acute hyperoxia on solute transport from air space to
      vascular space in isolated rat lungs. Air spaces were filled with Krebs-Ringer
      bicarbonate solution containing fluorescein isothiocyanate-labeled dextran (FD
      20; mol wt 20,000) and either 22Na+ and [14C]sucrose, or D-[14C]glucose and L
      [3H]glucose. Apparent permeability-surface area products for tracers over time
      (up to 120 min) were calculated for isolated perfused lungs from control rats
      (room air) and rats exposed to > 95% O2 for 48 or 60 h immediately postexposure.
      After O2 exposures, mean fluxes for [14C]sucrose and FD-20 were significantly
      higher than in room-air control lungs. However, amiloride-sensitive Na+ and
      active D-glucose fluxes were unchanged after hyperoxic exposure. Therefore, it is
      unlikely that decreases in net solute transport in this lung-injury model
      contributed to pulmonary edema resulting from O2 toxicity. Increased net solute
      transport shown to help resolve pulmonary edema after acute hyperoxic exposure
      must therefore begin during the recovery period. In summary, our data show
      increases in passive solute fluxes but no changes in active solute fluxes
      immediately after acute hyperoxic lung injury.

PMID- 9029223
TI  - Glucose administration before exercise modulates catecholaminergic responses in
      glycogen-depleted subjects.
AB  - In glycogen-depleted subjects (GD) a nonlinear increase in epinephrine (Epi) and
      norepinephrine (NE) parallels blood lactate (La) during graded exercise. The
      effect of glucose (Glc) supplementation and route of administration on these
      relationships was studied in 26 GD athletes who were randomly assigned to receive
      1.3 g/kg Glc by slow intravenous infusion (IV; n = 9), oral administration (PO; n
      = 9), or artificially sweetened placebo in 1 liter of water (Asp; n = 8) in the 2
      h preceding a graded maximal exercise. Performance and La were similar among the
      three groups in normal glycogen (NG) or GD conditions. However, slightly improved
      performances were observed in GD compared with NG and were associated with a
      shift to the right in La curves. Blood Glc concentrations were higher in IV and
      PO before exercise, but they rapidly decreased to lowest levels in IV, gradually
      decreased over time in PO, and remained stable in Asp or NG. Insulin
      concentrations were highest in IV and lowest in Asp and NG at onset of exercise,
      rapidly decreasing in IV and PO although remaining at higher levels than in Asp
      or NG. In contrast, higher serum levels of free fatty acids were measured during
      exercise in Asp with no significant differences in glucagon or glycerol among the
      three groups. Free and sulfated NE increases were smaller in IV than in PO and
      Asp on exhaustion. In contrast, free and conjugated Epi were most increased in
      IV, with smallest increases in Asp. Dopamine levels were most increased in IV at
      exhaustion. We conclude that the changes of Epi and NE concentrations, associated
      with the activation of glucoregulatory mechanisms, including hyperinsulinemia,
      display different magnitude and time courses during exercise in GD subjects who
      receive oral vs. intravenous load of Glc before exercise. We speculate that the
      magnitude of insulin surge after acutely increased Glc before exercise in GD
      subjects may exert dissociative effects on adrenal-dependent glycogenolysis and
      on sympathetic responses.

PMID- 9029224
TI  - Skeletal muscle mass and exercise performance in stable ambulatory patients with
      heart failure.
AB  - The purpose of this study was to determine whether skeletal muscle atrophy limits
      the maximal exercise capacity of stable ambulatory patients with heart failure.
      Body composition and maximal exercise capacity were measured in 100 stable
      ambulatory patients with heart failure. Body composition was assessed by using
      dual-energy X-ray absorption. Peak exercise oxygen consumption (VO2peak) and the
      anaerobic threshold were measured by using a Naughton treadmill protocol and a
      Medical Graphics CardioO2 System. VO2peak averaged 13.4 +/- 3.3 ml.min-1.kg-1 or
      43 +/- 12% of normal. Lean body mass averaged 52.9 +/- 10.5 kg and leg lean mass
      16.5 +/- 3.6 kg. Leg lean mass correlated linearly with VO2peak (r = 0.68, P <
      0.01), suggesting that exercise performance is influences by skeletal muscle
      mass. However, lean body mass was comparable to levels noted in 1,584 normal
      control subjects, suggesting no decrease in muscle mass. Leg muscle mass was
      comparable to levels noted in 34 normal control subjects, further supporting this
      conclusion. These findings suggest that exercise intolerance in stable ambulatory
      patients with heart failure is not due to skeletal muscle atrophy.

PMID- 9029225
TI  - Altered fractal dynamics of gait: reduced stride-interval correlations with aging
      and Huntington's disease.
AB  - Fluctuations in the duration of the gait cycle (the stride interval) display
      fractal dynamics and long-range correlations in healthy young adults. We
      hypothesized that these stride-interval correlations would be altered by changes
      in neurological function associated with aging and certain disease states. To
      test this hypothesis, we compared the stride-interval time series of 1) healthy
      elderly subjects and young controls and of 2) subjects with Huntington's disease
      and healthy controls. Using detrended fluctuation analysis we computed alpha, a
      measure of the degree to which one stride interval is correlated with previous
      and subsequent intervals over different time scales. The scaling exponent alpha
      was significantly lower in elderly subjects compared with young subjects
      (elderly: 0.68 +/- 0.14; young: 0.87 +/- 0.15; P < 0.003). The scaling exponent
      alpha was also smaller in the subjects with Huntington's disease compared with
      disease-free controls (Huntington's disease: 0.60 +/- 0.24; controls: 0.88 +/
      0.17; P < 0.005). Moreover, alpha was linearly related to degree of functional
      impairment in subjects with Huntington's disease (r = 0.78, P < 0.0005). These
      findings demonstrate that strike-interval fluctuations are more random (i.e.,
      less correlated) in elderly subjects and in subjects with Huntington's disease.
      Abnormal alterations in the fractal properties of gait dynamics are apparently
      associated with changes in central nervous system control.

PMID- 9029226
TI  - Training intensity, blood lipids, and apolipoproteins in men with high
      cholesterol.
AB  - Twenty-six hypercholesterolemic men (mean cholesterol, 258 mg/dl; age, 47 yr;
      weight, 81.9 kg) completed 24 wk of cycle ergometer training (3 days/wk, 350
      kcal/session) at either high (n = 12) or moderate (n = 14) intensity (80 and 50%
      maximal O2 uptake, respectively, randomly assigned) to test the influence of
      training intensity on blood lipid and apolipoprotein (apo) concentrations. All
      physiological, lipid, and apo measurements were completed at 0, 8, 16, and 24 wk.
      Lipid data were analyzed via two x four repeated-measures analysis of variance
      (alpha = 0.0031). Training produced a significant decrease in body weight and
      increase in maximal O2 uptake. No interactions between intensity and weeks of
      training were noted for any lipid or apo variable, and no between-group
      differences were significant before or throughout training. Therefore, intensity
      did not affect the training response. Regardless of intensity, apo AI and apo B
      fell 9 and 13%, respectively, by week 16 and remained lower through week 24 (P <
      0.0003). Total cholesterol fell transiently (-5.5%) by week 16 (P < 0.0021) but
      returned to initial levels by week 24. Triglyceride, low-density-lipoprotein
      cholesterol, and high-density-lipoprotein (HDL) cholesterol did not change with
      training. In contrast, HDL2 cholesterol rose 79% above initial levels by week 8
      and 82% above initial levels by week 24 (P < 0.0018); HDL3 cholesterol fell 8 and
      13% over the same training intervals (P < 0.0026). These data show that changes
      in blood lipid and apo concentrations that accompany training in
      hypercholesterolemic men are not influenced by exercise intensity when caloric
      expenditure is held constant.

PMID- 9029227
TI  - Pliometric contraction-induced injury of mouse skeletal muscle: effect of initial
      length.
AB  - For single pliometric (lengthening) contractions initiated from optimal fiber
      length (Lf), the most important factor determining the subsequent force deficit
      is the work input during the stretch. We tested the hypothesis that regardless of
      the initial length, the force deficit is primarily a function of the work input.
      Extensor digitorum longus muscles of mice were maximally activated in situ and
      lengthened at 2 Lf/s from one of three initial fiber lengths (90, 100, or 120% of
      Lf) to one of three final fiber lengths (150, 160, or 170% of Lf). Maximal
      isometric force production was assessed before and after the pliometric
      contraction. No single mechanical factor, including the work input (r2 = 0.34),
      was sufficient to explain the differences in force deficits observed among
      groups. Therefore, the force deficit appears to arise from a complex interaction
      of mechanical events. With the data grouped by initial fiber length, the
      correlation between the average work and the average force deficit was high (r2 =
      0.97-0.99). Consequently, differences in force deficits among groups were best
      explained on the basis of the initial fiber length and the work input during the
      stretch.

PMID- 9029228
TI  - Angiogenesis in bronchial circulatory system after unilateral pulmonary artery
      obstruction.
AB  - We studied the effects of left pulmonary artery (LPA) ligation on the bronchial
      circulatory system (BCS) by using a sheep model. LPA was ligated in the newborn
      lambs soon after birth (n = 8), and when the sheep were approximately 3 yr of age
      anatomic studies revealed marked angiogenesis in BCS. Bronchial blood flow and
      cardiac output were studied by placing flow probes around the bronchial and
      pulmonary arteries in four adult sheep. After LPA ligation, bronchial blood flow
      increased from 35 +/- 6 to 134 +/- 42 ml/min in approximately 3 wk (P < 0.05). We
      also studied gas-exchange functions of BCS approximately 3 yr after the ligation
      of LPA in newborn lambs (n = 4) and used a control group (n = 12) in which LPA
      was ligated acutely. In the left lung, O2 uptake after acute ligation was 16 +/-
      3 ml/min and was similar to the chronic model, whereas CO2 output in the control
      group was 27 +/- 3 ml/min compared with 79 +/- 12 ml/min in the chronic
      preparation (P < 0.05). We conclude that LPA ligation causes marked angiogenesis
      in BCS that is capable of performing some gas-exchange functions.

PMID- 9029229
TI  - Effect of N omega-nitro-L-arginine on ventilatory response to hypercapnia in
      anesthetized cats.
AB  - The effect of intravenous administration of 40 mg/kg N omega-nitro-L-arginine (L
      NNA), an inhibitor of the synthesis of nitric oxide (NO), on the ventilatory
      response to CO2 was studied in anesthetized cats. The ventilatory response to CO2
      was assessed during normoxia by applying square-wave changes in end-tidal PCO2 of
      approximately 1 kPa. Each CO2 response was separated into a fast peripheral and
      slow central component characterized by a CO2 sensitivity (Sp and Sc,
      respectively), time constant, time delay, and an offset (apneic threshold). L-NNA
      reduced Sp, Sc, and the apneic threshold significantly by approximately 30%.
      However, the ratio Sp/Sc was not changed. It is argued that the reduction in Sp
      and Sc, Sp/Sc remaining constant, may be due to a potent inhibitory action of L
      NNA on the brain stem respiratory-integrating centers and on the neuromechanical
      link between these centers and respiratory movements. It is concluded that NO
      plays an important role in the control of breathing.

PMID- 9029230
TI  - Effect of an 18-wk weight-training program on energy expenditure and physical
      activity.
AB  - The purpose of this study was to examine the effect of an 18-wk weight-training
      program on average daily metabolic rate (ADMR). Before the intervention and in
      weeks 8 and 18 (T0, T8, and T18, respectively) data on body composition, sleeping
      metabolic rate (SMR), food intake, energy cost of the weight-training program
      (EEex), and nontraining physical activity (accelerometer) were collected in the
      exercise group (EXER, n = 18 males). ADMR was determined in a subgroup (EX12, n =
      12) by using doubly labeled water. At T0 and T18, data (except ADMR) were also
      collected in a control group (Con, n = 8). Body mass did not change in EXER or
      Con. Fat-free mass increased only in EXER with 2.1 +/- 1.2 kg, whereas fat mass
      decreased in EXER as well as Con (2.0 +/- 1.8 and 1.4 +/- 1.0 kg, respectively).
      Initial ADMR (12.4 +/- 1.2 MJ/day) increased at T8 (13.5 +/- 1.3 MJ/day, P <
      0.001) with no further increase at T18 (13.5 +/- 1.9 MJ/day). SMR did not change
      in EXER (4.8 +/- 0.5, 4.9 +/- 0.5, 4.8 +/- 0.5 kJ/min) or Con (4.7 +/- 0.4, 4.8
      +/- 0.4 kJ/min). Energy intake did not change in EXER (10.1 +/- 1.8, 9.7 +/- 1.8,
      9.2 +/- 1.9 MJ/day) or Con (10.2 +/- 2.6, 9.4 +/- 1.8, 10.1 +/- 1.5 MJ/day) and
      was systematically underreported in EX12 (-21 +/- 14, -28 +/- 18, -34 +/- 14%, P
      < 0.001). EEex (0.47 +/- 0.20, 0.50 +/- 0.18 MJ/day) could only explain 40% of
      the increase in ADMR. Nontraining physical activity did not change in both
      groups. In conclusion, although of modest energy cost, weight-training induces a
      significant increase in ADMR.

PMID- 9029231
TI  - Exhalation of gaseous nitric oxide by rats in response to endotoxin and its
      absorption by the lungs.
AB  - Rats injected with a lipopolysaccharide endotoxin produce detectable
      concentrations of nitric oxide gas (NO) in the expired air within 60 min. The
      concentration of NO reaches a plateau at 3 h. Production of the NO is dose
      dependent on lipopolysaccharide, and at a dose of 1 mg/kg i.v.,
      lipopolysaccharide alveolar concentrations of > 260 parts per billion are
      observed. NO synthase inhibitors suppress this NO production in response to
      endotoxin. Experiments were conducted to ascertain the site of origin of this NO
      and to measure the capacity of the lungs to absorb NO from alveolar air. Results
      indicate that the endotoxin-induced NO originates from within the lungs
      themselves and that the lungs have the capacity to absorb > 60% of NO that is
      presented to them. Lung tissues absorb approximately 44-47% of the NO load, blood
      carries away between 15 and 19%, while the remainder is exhaled in the expired
      air. It is proposed that the exhalation of NO might prove useful as an early
      biomarker for acute lung injury.

PMID- 9029232
TI  - Ventilation and metabolism among rat strains.
AB  - We examined ventilation and metabolism in four rat strains with variation in
      traits for body weight and/or blood pressure regulation. Sprague-Dawley [SD; 8
      males (M), 8 females (F)], Brown Norway (BN; 10 M, 11 F), and Zucker (Z; 11 M, 12
      F) rats were compared with Koletsky (K; 11 M, 11 F) rats. With the use of
      noninvasive plethysmography, frequency, tidal volume, minute ventilation (VE), O2
      consumption, and CO2 production were derived at rest during normoxia (room air)
      and during the 5th minute of exposure to each of the following: hyperoxia (100%
      O2), hypoxia (10% O2-balance N2), and hypercapnia (7% CO2-balance O2).
      Statistical methods probed for strain and sex effects, with covariant analysis by
      body weight, length, and body mass. During resting breathing, strain effects were
      found with respect to both frequency (BN, Z > K, SD) and tidal volume (SD > BN,
      Z) but not to VE. Sex influenced frequency (F > M) alone. Z rats had higher
      values for O2 consumption, CO2 production, and respiratory quotient than the
      other three strains, with no independent effect by sex. During hyperoxia,
      frequency was greater in BN and Z than in SD or K rats; SD rats had a larger
      tidal volume than BN or Z rats; Z rats had a greater VE than K rats; and M had a
      larger tidal volume than F. Strain differences persisted during hypercapnia, with
      Z rats exhibiting the highest frequency and VE values. During hypoxic exposure,
      strain effects were found to influence VE (SD > K, Z), frequency (BN > K), and
      tidal volume (SD > BN, K, Z). Body mass was only a modest predictor of VE during
      normoxia, of both VE and tidal volume with hypoxia, hypercapnia, or hyperoxia,
      and of frequency during hypercapnia. We conclude that strain of rats, more than
      their body mass or sex, has major and different influences on metabolism, the
      pattern and level of ventilation during air breathing, and ventilation during
      acute exposure to hypercapnia or hypoxia.

PMID- 9029233
TI  - Eglin-c prevents monocrotaline-induced ventilatory dysfunction.
AB  - The present study was carried out to investigate the relationship between
      elastase and monocrotaline (MCT)-induced ventilatory dysfunction in rats. To
      accomplish this, we used an elastase inhibitor eglin-c to suppress the activity
      of endogenous elastase. Thirty-five young Sprague-Dawley rats were randomly
      divided into six groups: control, MCT, eglin-c(1), eglin-c(2), eglin-c(1) + MCT,
      and eglin-c(2) + MCT. Rats in the control group received no treatment. Each MCT
      rat received a single subcutaneous injection of MCT (60 mg/kg) 1 wk before the
      functional test. Each eglin-c(1) rat was intratracheally instilled with eglin-c
      (9 mg/rat) twice in 1 wk. Each eglin-c(2) rat was intratracheally instilled with
      eglin-c (9 mg/rat) five times in 1 wk. Both eglin-c + MCT groups were treated
      with the combination of eglin-c(1) or eglin-c(2) and MCT. In the MCT group, there
      were significant decreases in dynamic respiratory compliance, maximal expiratory
      flow rate at 50% total lung capacity, and the slopes of the maximal expiratory
      flow-%total lung capacity curve and the maximal expiratory flow-static recoil
      pressure curve. However, in the eglin-c(1) + MCT and eglin-c(2) + MCT groups, all
      of the above-mentioned MCT-induced changes were prevented. All ventilatory values
      of the eglin-c(1) and eglin-c(2) groups were not significantly different from
      those of the control group. These results demonstrate that eglin-c treatment
      prevents MCT-induced ventilatory dysfunction and suggest that endogenous elastase
      may play an important role in MCT-induced inflammation-mediated ventilatory
      abnormality.

PMID- 9029234
TI  - A model for phosphocreatine resynthesis.
AB  - A model for phosphocreatine (PCr) resynthesis is proposed based on a simple
      electric circuit, where the PCr store in muscle is likened to the stored charge
      on the capacitor. The solution to the second-order differential equation that
      describes the potential around the circuit suggests the model for PCr resynthesis
      is given by PCr(t) = R - [d1.exp(-k1.t) +/- d2.exp(-k2.t)], where R is PCr
      concentration at rest, d1, d2, k1, and k2 are constants, and t is time. By using
      nonlinear least squares regression, this double-exponential model was shown to
      fit the PCr recovery data taken from two studies involving maximal exercise
      accurately. In study 1, when the muscle was electrically stimulated while
      occluded, PCr concentrations rose during the recovery phase to a level above that
      observed at rest. In study 2, after intensive dynamic exercise, PCr recovered
      monotonically to resting concentrations. The second exponential term in the
      double-exponential model was found to make a significant additional contribution
      to the quality of fit in both study 1(P < 0.05) and study 2(P < 0.01).

PMID- 9029235
TI  - Whole body sweat collection in humans: an improved method with preliminary data
      on electrolyte content.
AB  - Previous methods used to collect human sweat for electrolyte analysis have been
      criticized because they involve only regional sampling or because of
      methodological problems associated with whole body-washdown techniques. An
      improved method for collection of whole body sweat from exercising subjects is
      described. It involved construction of a plastic frame that supports a large
      plastic bag within which the subject exercises. The subject and the equipment are
      washed with distilled, deionized water before exercise begins. After exercise is
      completed, the subject and equipment are again washed with water containing a
      marker not present in sweat (ammonium sulfate). Total sweat loss is calculated
      from the change in body mass, and the volume of sweat not evaporated is
      calculated from dilution of the added marker. Recovery of added water was 102 +/-
      2% (SD) of the added volume, and recovery of added electrolytes was 99 +/- 2% for
      sodium, 98 +/- 9% for potassium, and 101 +/- 4% for chloride. Repeated trials (n
      = 4) on five subjects to establish the reproducibility of the method gave a
      coefficient of variation of 17 +/- 5% for sodium, 23 +/- 6% for potassium, and 15
      +/- 6% for chloride. These values include the biological variability between
      trials as well as the error within the method. The biological variability thus
      appears to be far greater than the methodological error. Normal values for the
      composition of sweat induced by exercise in a hot, humid environment in healthy
      young men and women were (in mM) 50.8 +/- 16.5 sodium, 4.8 +/- 1.6 potassium, 1.3
      +/- 0.9 calcium, 0.5 +/- 0.5 magnesium, and 46.6 +/- 13.1 chloride.

PMID- 9029236
TI  - Persistence of supercompensated muscle glycogen in trained subjects after
      carbohydrate loading.
AB  - Several carbohydrate (CHO)-loading protocols have been used to achieve muscle
      glycogen supercompensation and prolong endurance performance. This study assessed
      the persistence of muscle glycogen supercompensation over the 3 days after the
      supercompensation protocol. Trained male athletes completed a 6-day CHO-loading
      protocol that included cycle ergometer exercise and dietary manipulations. The 3
      day depletion phase began with 115 min of cycling at 75% peak oxygen uptake
      followed by 3 x 60-s sprints and included the subjects consuming a low-CHO/high
      protein/high-fat (10:41:49%) diet. Subjects cycled 40 min at the same intensity
      for the next 2 days. During the 3-day repletion phase, subjects rested and
      consumed a high-CHO/low-protein/low-fat (85:08:07%) diet, including a glucose
      polymer beverage. A 3-day postloading phase followed, which involved a moderately
      high CHO diet (60%) and no exercise. Glycogen values for vastus lateralis
      biopsies at baseline and postloading days 1-3 were 408 +/- 168 (SD), 729 +/- 222,
      648 +/- 186, and 714 +/- 196 mmol/kg dry wt, respectively. The CHO-loading
      protocol increased muscle glycogen by 1.79 times baseline, and muscle glycogen
      remained near this level during the 3-day postloading period. Results indicate
      that supercompensated muscle glycogen levels can be maintained for at least 3
      days in a resting athlete when a moderate-CHO diet is consumed.

PMID- 9029237
TI  - Alveolar liquid clearance in multiple nonperfused canine lung lobes.
AB  - We evaluated the ability of canine isolated nonperfused lung lobes to absorb
      fluid from their air spaces by simultaneously measuring alveolar liquid clearance
      (ALC) in three lobes removed from the same dog. Autologous plasma was instilled
      in the air spaces of each lobe, and the increase in plasma protein concentration
      resulting from fluid reabsorption was used to calculate ALC. ALC after 4 h was
      16.5 +/- 0.6% (SE) of the instilled fluid volume under baseline conditions and
      was 30.2 +/- 1.3% after terbutaline (10(-5) M) administration. These values were
      similar to those previously reported for intact dogs. Propranolol (10(-4) M) and
      ouabain (10(-3) M) reduced ALC in terbutaline-stimulated lobes to 20.4 +/- 0.8
      and 3.9 +/- 1.4%, respectively. There was no significant difference in ALC among
      the three lobes under either baseline conditions or after terbutaline
      administration. These data indicate that the sodium and water transport
      mechanisms of the canine alveolar epithelium remain viable during 4 h of
      nonperfusion and that there are no intrinsic differences in the transport
      properties of individual lung lobes. The ability to study several lobes
      simultaneously without the need for perfusion will allow for the design of
      experiments in which multiple interventions can be studied by using lung lobes
      from the same animal.

PMID- 9029238
TI  - Determination of fascicle length and pennation in a contracting human muscle in
      vivo.
AB  - We have developed a technique to determine fascicle length in human vastus
      lateralis muscle in vivo by using ultrasonography. When the subjects had the knee
      fully extended passively from a position of 110 degree flexion (relaxed
      condition), the fascicle length decreased from 133 to 97 mm on average. During
      static contractions at 10% of maximal voluntary contraction strength (tensed
      condition), fascicle shortening was more pronounced (from 126 to 67 mm),
      especially when the knee was closer to full extension. Similarly, as the knee was
      extended, the angle of pennation (fascicle angle, defined as the angle between
      fascicles and aponeurosis) increased (relaxed, from 14 to 18 degrees; tensed,
      from 14 to 21 degrees), and a greater increase in the pennation angle was
      observed in the tensed than in the relaxed condition when the knee was close to
      extension (< 40 degrees). We conclude that there are differences in fascicle
      lengths and pennation angles when the muscle is in a relaxed and isometrically
      tensed conditions and that the differences are affected by joint angles, at least
      at the submaximal contraction level.

PMID- 9029239
TI  - Evidence that nitric oxide increases glucose transport in skeletal muscle.
AB  - Nitric oxide synthase (NOS) is expressed in skeletal muscle. However, the role of
      nitric oxide (NO) in glucose transport in this tissue remains unclear. To
      determine the role of NO in modulating glucose transport, 2-deoxyglucose (2-DG)
      transport was measured in rat extensor digitorum longus (EDL) muscles that were
      exposed to either a maximally stimulating concentration of insulin or to an
      electrical stimulation protocol, in the presence of NG-monomethyl-L-arginine, a
      NOS inhibitor. In addition, EDL preparations were exposed to sodium nitroprusside
      (SNP), an NO donor, in the presence of submaximal and maximally stimulating
      concentrations of insulin. NOS inhibition reduced both basal and exercise
      enhanced 2-DG transport but had no effect on insulin-stimulated 2-DG transport.
      Furthermore, SNP increased 2-DG transport in a dose-responsive manner. The
      effects of SNP and insulin on 2-DG transport were additive when insulin was
      present in physiological but not in pharmacological concentrations. Chronic
      treadmill training increased protein expression of both type I and type III NOS
      in soleus muscle homogenates. Our results suggest that NO may be a potential
      mediator of exercise-induced glucose transport.

PMID- 9029240
TI  - Plasma 2-hydroxycatecholestrogen responses to acute submaximal and maximal
      exercise in untrained women.
AB  - Exercise-induced menstrual problems are accompanied by an increase in
      catecholestrogen (CE) formation. It has been hypothesized that hypoestrogenemia
      may be secondary to an increased turnover from estrogens to CE, which then may
      disrupt luteinizing hormone release. In addition, the strong affinity of CE for
      the catecholamine-deactivating enzyme catechol-O-methyltransferase (COMT) has led
      to speculations about their possible role in safeguarding norepinephrine from
      premature decomposition during exercise. We investigated whether acute exercise
      on a cycle ergometer produces any changes in CE homeostasis. Nine untrained
      eumenorrheic women (body fat, 24.8 +/- 3.1%) volunteered for this study. Baseline
      plasma CE averages for total 2-hydroxyestrogens (2-OHE) were 218 +/- 29 (SE)
      pg/ml during the follicular phase (FPh) and 420 +/- 58 pg/ml during the luteal
      phase (LPh). 2-Methoxyestrogens (2-MeOE) measured 257 +/- 17 pg/ml in the FPh and
      339 +/- 39 pg/ml in the LPh. During incremental exercise, total estrogens (E)
      increased, but 2-OHE and 2-MeOE levels did not significantly change in either
      phase. The 2-OHE/E ratio (measure of CE turnover) decreased during exercise in
      both menstrual phases, whereas the 2-MeOE/2-OHE ratio (correlates with COMT
      activity) did not significantly change. These findings suggest that there is
      insufficient evidence to conclude that brief incremental exercise in untrained
      eumenorrheic females acutely produces increased CE formation.

PMID- 9029241
TI  - Role of carotid body activity responsible for hypoxic ventilatory decline in
      awake humans.

PMID- 9029242
TI  - Hypertension in the dialysis population: no easy answers.

PMID- 9029243
TI  - Peritonitis: finding success by evaluating the failures.

PMID- 9029244
TI  - Medical and dialytic management of hyperkalemia in hemodialysis patients.

PMID- 9029245
TI  - Effects of a pH 7.4, lactate-based and a pH 7.4, bicarbonate-based peritoneal
      dialysis solutions on neutrophil superoxide generation.
AB  - Neutrophil superoxide formation was similar when cells were incubated in self
      made, non-autoclaved pH 7.4, lactate-based peritoneal dialysis solutions or in
      their self-made, non-autoclaved, pH 7.4, bicarbonate-based counterparts. On the
      other hand, commercially available, autoclaved, pH 7.4, lactate-based peritoneal
      dialysis solutions resulted in inhibition of superoxide production when compared
      to their self-made, non-autoclaved, pH 7.4, lactate-based or bicarbonate-based
      counterparts. The cause for this inhibition of superoxide generation is at
      present unknown.

PMID- 9029246
TI  - Removal of constitutive and inducible nitric oxide synthase-active compounds in a
      modified hemodiafiltration with on-line production of substitution fluid: the
      contribution of convection and diffusion.
AB  - Chronic renal failure and the uremic state lead to accumulation of various
      endogenous inhibitors of nitric oxide synthase. Previous studies on end-stage
      uremic patients nitric oxide synthase activity in murine vascular endothelium and
      cytokine-induced macrophage cell lines was shown to be modulated during treatment
      (Nephrol Dial Transplant 1995; 10: 1386-96). Paired filtration dialysis, a
      modified hemodiafiltration technique, physically separates convection from
      diffusion. Plasmas, ultrafiltrates and dialysates from seven uremic patients
      undergoing paired filtration dialysis performed using ultrapure apyrogen
      substitution fluid in the absence (first 120 min) or presence (last 120 min) of
      extracellular fluid reduction were tested for their inhibitory/stimulatory effect
      on ecNOS, constitutively expressed on t.End 1 cell line, a murine vascular
      endothelium, or for their inducing effect on iNOS, inducible on J774 cells, a
      macrophage cell line. On ecNOS, Group 1 (stimulatory, 3/7 patients) markedly
      enhanced the ecNOS activity as compared to control plasma, whereas group 2 plasma
      (inhibitory, 4/7 patients) inhibited ecNOS plasma. Post-dialysis plasma samples
      from all Group 1 and 2 patients showed a marked decrease of the predialysis
      stimulatory and inhibitory activity, respectively. On iNOS: all patient plasmas
      stimulated iNOS activity. The UF and particularly the dialysate had a remarkable
      iNOS inducing effect (Group 1). The substitution fluid obtained at 120 min during
      treatment in Group 1 and 2 had no effect on NOS activity. No correlation was
      found between predialysis ecNOS or iNOS activity values with mean systolic or
      diastolic pressures. These studies suggest a complex balance of ecNOS
      inhibitors/stimulators and iNOS inducers in uremia. Dialysis may remove ecNOS
      inhibitors and stimulators by convection and, in the latter case, by diffusion.
      iNOS inducers are removed during dialysis, suggesting the biocompatibility of the
      dialysis system with the on-line production of ultrapure substitution fluid.

PMID- 9029247
TI  - A new polymer valve for mechanical circulatory support systems.
AB  - A new low-cost artificial heart valve with easily modified dimensions according
      to its application was developed using segmented polyurethane (SPU). It consists
      of a convex frame and a concave membrane which floats in the center of the frame
      while working. The hydrodynamic performance of the polymer valve was compared
      with that of the Bjork-Shiley mechanical valve using a mock circulatory testing
      system. The hydrodynamic performance of this valve was superior to the Bjork
      Shiley mechanical valve. The valve was applied to a ventricular assist device
      (VAD) developed in our institute. In vivo performances of these systems were
      tested using mongrel dogs. During the experiments, there were no complications
      related to malfunction of the valve. At postmortem examinations, no thrombus
      formation was found on the valve surface, and no embolus was detected in the
      kidneys. We believe this valve could prove a very useful alternative for valves
      of mechanical circulatory support systems (MCSS) such as VAD and TAH.

PMID- 9029249
TI  - Implantable insulin pumps: diagnosis and management of decreased flow rates using
      radionuclide investigation.
AB  - The aim of this study was to develop a diagnostic procedure for pumping unit
      malfunction by radionuclide imaging (RI) and to validate the method by comparing
      the results with those obtained using more conventional methods. Fifteen
      radionuclide investigations were performed in 11 patients with intraperitoneal
      implantable insulin pumps. One mCi of 99 mTc in 1 ml isotonic sodium chloride was
      injected into the reservoir. The results based on catheter visualization and
      peritoneal accumulation were compared blindly to the efficacy of alkaline rinses
      and laparoscopic findings. In all RI stoppage cases except one alkaline rinses
      failed to restore flow. Where laparoscopy was performed, comparisons were
      concordant i.e. no outflow from the tip of the catheter. The RI images obtained
      were reproduced in vitro using a pump under normal flow conditions and complete
      proximal and distal catheter obstruction. RI is a safe, quick non invasive method
      which allows the location of the site of pump/catheter malfunction within a one
      step procedure and the prediction of the efficacy of sodium hydroxide rinses.

PMID- 9029248
TI  - A computer controlled pulsatile pump: preliminary study.
AB  - A Stepper Motor Driven Reciprocating Pump (SDRP) can replace roller pumps and
      rotary pumps for cardio pulmonary bypass, hemodialysis and regional perfusion.
      The blood pumping ventricles are basically the same as ventricles used for air
      driven artificial hearts and ventricular assist devices. The electric stepper
      motor uses a flexible linkage belt to produce a reciprocating movement, which
      pushes a hard sphere into the diaphragm of the blood ventricles. The SDRP
      generates pulsatile flow and has a small priming volume. The preset power level
      of the motor driver limits the maximum potential outflow pressure, so the driver
      acts as a safety device. A double pump can be made by connecting two fluid
      pumping chambers to opposing sides of the motor base. Each pump generates
      pulsatile flow. Pressure and flow studies with water were undertaken. Preliminary
      blood studies showed low hemolysis, even when circulating a small amount of blood
      up to 16 hours.

PMID- 9029251
TI  - Transplantation of parathyroid tissue in experimental hypoparathyroidism: in
      vitro and in vivo function of parathyroid tissue microencapsulated with a novel
      amitogenic alginate.
AB  - Microencapsulation of tissues is an alternative to postoperative
      immunosuppression in transplantation. In 1994 iso-, allo- and xenotransplantation
      of microencapsulated parathyroid tissue was achieved in vivo. However, continued
      analysis of the coating substance (an alginate) determined mitogenic properties.
      Here, we report on the in vitro and in vivo function of parathyroid tissue
      microencapsulated with a novel amitogenic alginate suitable for use in humans. To
      assess in vitro function, parathyroid tissue encapsulated with mitogenic and
      amitogenic alginate was exposed to rising concentrations of calcium. For in vivo
      experiments, it was isotransplanted into parathyroidectomized rats. PTH release
      into medium and PTH serum levels as well as calcium levels of recipient rats were
      analyzed and compared to native (non-microencapsulated) tissue and empty
      capsules, respectively. In vivo, transplants were excised and subjected to
      histologic examination six months after trans-plantation. In vitro, parathyroid
      tissue encapsulated with amitogenic alginate releases approximately half of the
      PTH of the native tissue, not different from tissue encapsulated with the
      mitogenic alginate. In vivo, the novel alginate preserved parathyroid function
      similar to that of native tissue over the six month period resulting in complete
      reversal of hypoparathyroidism. Correspondingly, histologic examination revealed
      vital parathyroid tissue in intact microcapsules. By establishing in vitro
      function and successful long-term transplantation, we have documented the
      principle of microencapsulation of parathyroid tissue to be effective also with
      the novel amitogenic alginate, which is suitable for clinical use.

PMID- 9029250
TI  - Pathophysiological and histomorphological evaluation of polyacryloylmorpholine vs
      polyethylene glycol modified superoxide dismutase in a rat model of
      ischaemia/reperfusion injury.
AB  - Twenty Wistar rats were divided into two groups. Both underwent acute ischaemia
      followed by reperfusion of the left hind limb. The first group was a control
      group while the second was treated with PAcM-SOD. The survival percentage of the
      limb after 10 days was 30% for the first group and 70% for the second. Neither
      linear regression nor correlation were found between groups as far as the
      survival percentage of the limb after 10 days and reperfusion pmO2 data were
      concerned. After ten days the histomorphological analysis was significant
      regarding the fibre diameter and the percentage of central located nuclei in the
      specimens of PAcM-SOD treated limbs compared to normal limbs, but not when
      compared to the muscular fibres of the control group. Comparing these results
      with others obtained with native SOD and monomethoxypoly(ethylene glycol)
      modified SOD (mPEG-SOD) used in the same experimental model, we can conclude that
      the clinical and morphological results were better using mPEG-SOD, and that PAcM
      SOD does have a protective effect on ischaemic muscle damage, although it is not
      as effective as mPEG-SOD in preventing ischaemia/reperfusion injury.

PMID- 9029252
TI  - Purification of bacteriocins of lactic acid bacteria: problems and pointers.
AB  - Bacteriocins of lactic acid bacteria have been widely studied in recent years.
      However, there are relatively few studies that describes their biochemical
      structure. This study may be due to the many challenges associated with the
      purification of these antimicrobial peptides. This review focuses on the
      purification procedures used with bacteriocins of lactic acid bacteria and
      conveys some of the problems associated with this process as well as some of the
      lessons learned. An improvement in the efficiency of the purification process
      should contribute significantly to research at the understanding of the
      biochemical nature of bacteriocins.

PMID- 9029253
TI  - Aeromonas species in fish, fish-eggs, shrimp and freshwater.
AB  - Aeromonas spp. are common contaminants of fish and seafood. They also are
      ubiquitous in the water environment. Aeromonas spp. were identified in 27 (93%)
      of 29 fish, in 17 (100%) fish-egg, in two (16%) of 12 shrimp samples and in 23
      (100%) freshwater samples. In total, 117 Aeromonas strains were isolated from 69
      positive samples, several samples having had two or three Aeromonas species.
      Included in this were also 26 mesophilic Aeromonas strains isolated in
      association with the study on fish diseases. The distribution of the species into
      13 known hybridization groups (HGs) were studied by phenotypic and molecular
      methods. Ribopattern analysis of SmaI digested DNA was used for the
      identification of HGs. The predominant HG in fish, fish-eggs and freshwater
      samples was A. hydrophila HG 3 because 63% (22/37), 28% (16/57) or 80% (16/20) of
      the strains, respectively, were in HG 3. A. hydrophila HG 2 was also common in
      fresh fish samples but was not identified in fish-egg samples. HG 7 was common in
      fish samples studied for fish diseases and in freshwater samples. Strains which
      were not allotted to any HGs were common (19 of 143 strains). A. hydrophila HG 1,
      A. caviae HG 4, A. veronii subspecies sobria or subspecies veronii HG 8/10 known
      to be associated with human diarrhea were uncommon in all samples. The three
      strains isolated from frozen shrimp during two suspected food-borne outbreaks
      were A. hydrophila HG 2 and HG 3.

PMID- 9029254
TI  - Computational neural networks for predictive microbiology: I. Methodology.
AB  - Artificial neural networks are mathematical tools inspired by what is known about
      the physical structure and mechanism of the biological cognition and learning.
      Neural networks have attracted considerable attention due to their efficacy to
      model wide spectrum of challenging problems. In this paper, we present one of the
      most popular networks, the backpropagation, and discuss its learning algorithm
      and analyze several issues necessary for designating optimal networks that can
      generalize after being trained on examples. As an application in the area of
      predictive microbiology, modeling of microorganism growth by neural networks will
      be presented in a second paper of this series.

PMID- 9029255
TI  - Computational neural networks for predictive microbiology. II. Application to
      microbial growth.
AB  - The growth of a specific microorganism on a certain food is influenced by a
      number of environmental factors such as temperature, pH, and salt concentration.
      Methods that delineate the history of the growth of microorganisms are always
      subject to a considerable debate and scrutiny in the field of predictive
      microbiology. Regardless of its types, a growth model (e.g., modified Gompertz
      model) contains several parameters that vary depending on the microorganisms/food
      combination and the associated prevailing environmental conditions. The growth
      model parameters for a set of operating conditions are commonly determined from
      expressions developed via multiple linear regressions. In the present study, a
      substitute for the nonlinear regression-based equations is developed using
      computational neural networks. Computational neural networks are applied herein
      on experimental data pertaining to the anaerobic growth of Shigella flexneri.
      Results have indicated that predictions by neural networks offer better agreement
      with experimental data as compared to predictions obtained via corresponding
      regression equations.

PMID- 9029256
TI  - Reliability and practicability of bacteriological monitoring of beef carcass
      contamination and their rating within a hygiene quality control programme of
      abattoirs.
AB  - A total of 9600 swab samples from 900 carcasses originating from ten different
      abattoirs were subjected to bacteriological examination. Two sampling sites,
      brisket and forearm, consistently showed the highest contamination rates. The
      following sites are recommended for sampling: on the lateral side of the carcass
      neck, forearm, shoulder, brisket and abdomen. The neck is recommended for the
      medial side. Compared to the large variance of contamination either on individual
      carcasses or between different carcasses, the differences in the variance of
      results between double swab and incision sampling techniques should be of minor
      importance. Considering this big variance of colony counts, it is suggested to
      take five to six swab samples from each of at least ten to 15 carcasses once a
      month. With a view to a more differentiated and evident evaluation the results
      should be recorded in a 'box plots' and not in the form of mean values and
      standard deviations. The data confirms bacteriological monitoring of beef
      carcasses as a useful tool for the verification of slaughter hygiene.

PMID- 9029257
TI  - Genotypic diversity of Campylobacter lari isolated from mussels and oysters in
      The Netherlands.
AB  - In order to gain insight into the epidemiology of Campylobacter lari infection in
      The Netherlands due to the consumption of raw mussels and oysters, batches of
      these shellfish were screened for the presence of Campylobacter spp. during a 6
      month period in 1993-1994. Apparently, 41 out of 59 batches of mussels and 11 out
      of 41 batches of oysters were colonized with Campylobacter spp. A subset of the
      isolates was further characterized by additional phenotypic tests, numerical
      analysis of electrophoretic protein patterns, and genotyping by random
      amplification of polymorphic DNA (RAPD). Protein electrophoretic analysis of 39
      Campylobacter spp. cultured from 24 batches of mussels and oysters, revealed that
      all isolates, except two, were C. lari. Two strains with an aberrant protein
      pattern were identified as C. coli and C. hyointestinalis, respectively.
      Nalidixic acid susceptible campylobacters (NASC) and urease-positive thermophylic
      campylobacters (UPTC) did not form separate clusters and should be considered
      biovars only. Several strains were both urease positive and nalidixic acid
      susceptible, which represents a new biovar within C. lari. The results of RAPD
      demonstrated the presence of 3 distinct genetic variants, implying that even
      within a single batch of shell fish, relatively extensive DNA polymorphisms can
      be found. It is therefore apparent that this complex group of C. lari is
      characterized by a high degree of genetic diversity, implying the presence of a
      heterogenous population of C. lari in crustacean organisms living in marine
      waters in a restricted area in The Netherlands.

PMID- 9029258
TI  - The effect of previous growth conditions on the lag phase time of some foodborne
      pathogenic micro-organisms.
AB  - In current models for predicting microbial growth, the lag phase duration is
      expressed as a function of the growth rate of the micro-organism. We observed
      that in addition to the growth rate (as influenced by incubation temperature and
      NaCl contents), the pre-incubation temperature influences the lag phase duration
      of foodborne pathogenic micro-organisms.

PMID- 9029259
TI  - Fluorogenic substrates for proteases based on intramolecular fluorescence energy
      transfer (IFETS).
AB  - A prospective class of intramolecular fluorescence energy transfer substrates
      (IFETS) is described. In contrast to the known chromogenic and fluorogenic
      substrates that are used widely in the scientific and medical research, IFETS
      allow to control the enzymatic cleavage at any point of the peptide chain and
      thus permit simultaneous studies of enzymes of different specificity. We discuss
      the main types of donor and acceptor, their advantages and drawbacks and the
      effectiveness of exited-state energy transfer between them. High sensitivity and
      selectivity of IFETS in the assay of proteinases was demonstrated. They prove to
      be a very useful and very promising instrument for enzymology and medicine.

PMID- 9029260
TI  - Improved resolution in the gel electrophoresis of proteins by a periodically
      interrupted electric field.
AB  - The capability of the commercial gel electrophoresis apparatus with intermittent
      scanning of fluorescence (HPGE-1000, LabIntelligence) to provide time-dependent
      zone dispersion allows one to quantitate resolution. Using a model protein
      separation, that between phycoerythrin and fluorescein-labeled conalbumin,
      resolution was compared between separations conducted at a constant field
      strength of 80 V/cm and one conducted in 10-s pulses of the same field strength,
      interrupted periodically by 120 s in the absence of an electric field. Resolution
      was improved by a factor of two in the discontinuous application of the electric
      field compared to that obtained in its continuous application. Similarly, the
      intermittent application of 80 V/cm for 10 s, followed by 120-s pauses, gave rise
      to twice the resolution obtained from a continuous application of 7 V/cm.

PMID- 9029261
TI  - Proteolytic cleavage of soybean Bowman-Birk inhibitor monitored by means of high
      performance capillary electrophoresis. Implications for the mechanism of
      proteinase inhibitors.
AB  - The hydrolysis of the soybean Bowman-Birk inhibitor in the presence of catalytic
      amounts of bovine trypsin and the formation of the non-covalent enzyme-inhibitor
      complex with an equimolar amount of enzyme are monitored by means of high
      performance capillary electrophoresis (HPCE). The inhibitor is cleaved in the
      trypsin-reactive and more slowly in the chymotrypsin-reactive subdomain. HPCE
      proves itself as the only reliable analytical tool to monitor these reactions in
      clear contrast to classical electrophoretic, chromatographic and enzymatic
      methods. The most efficient separation of the intact and the two active site
      cleaved forms of the inhibitor was achieved in borate buffer at pH 10.0. The pH
      dependence of the rate constant and the final extent of hydrolysis reveal the
      stability of the enzyme inhibitor complex as a central aspect of the mechanism of
      proteinase inhibitors.

PMID- 9029262
TI  - Application of an eosin B dye method for estimating a wide range of proteins.
AB  - We describe a detailed procedure for estimating a wide range of proteins by the
      eosin B dye method. At acidic pH, eosin B binds to proteins and absorption of the
      protein-dye complex at 536-544 nm is proportional to the concentration of the
      proteins. Inorganic and organic acids are used for the assay, the optimum
      concentration of acid for each assay differs from acid to acid. This method
      provides minimal interference with commonly used compounds in protein
      purification and biomolecules like DNA, RNA, lipids, carbohydrates and minerals
      which are generally present in biological fluids. This method is applicable for
      estimating proteins in tissue homogenates, isolated proteins and various
      biological fluids.

PMID- 9029263
TI  - A fluorogenic substrate for beta-glucuronidase: applications in fluorometric,
      polyacrylamide gel and histochemical assays.
AB  - We have developed a fluorogenic substrate, ELF-97 beta-D-glucuronide, that
      provides significant advantages over existing substrates in detecting beta
      glucuronidase activity. ELF-97 beta-D-glucuronide allows the detection of
      enzymatic activity in situ, yielding a hydrolytic product that exhibits maximal
      fluorescence within the physiological pH range. This substrate yields a
      hydrolytic product that demonstrates a more than 100 nm Stokes shift, which
      minimizes interference from autofluorescence in plant tissue. With the commercial
      enzyme, ELF-97 beta-D-glucuronide can detect less than 2 x 10(-4) U/ml of beta
      glucuronidase activity in solution, and 5 x 10(-4) U per lane in polyacrylamide
      gels. Assays using transgenic Arabidopsis, whole leaf extracts of GUS-positive,
      but not GUS-negative plans, show significant GUS activity upon incubation with
      ELF-97 beta-D-glucuronide. Furthermore, the ability of this substrate to form
      insoluble precipitates at the sites of enzymatic activity makes it suitable for
      in situ localization of GUS activity in tissue samples of higher plants.

PMID- 9029264
TI  - A magnetic micromethod to measure Young's modulus of protein crystals and other
      polymer materials.
AB  - A new micromethod has been developed to measure the elastic modulus of polymer
      materials. It is based on measurements of bending of a polymer sample in a
      periodic uneven magnetic field acting on a small permanent magnet attached to the
      sample free end. As compared to the other methods known, it combines simplicity
      of resonant methods with a possibility to perform measurements at different
      frequencies in liquids under normal and high pressures. The method is
      specifically designed to measure the temperature dependence of cross-linked
      protein crystals under different conditions.

PMID- 9029265
TI  - The use of crude tissue section lysates for PCR assessment of gene copy number
      with human tumour biopsy samples.
AB  - This paper reports the development of experimental procedures for the use of
      crude tissue section lysates, in conjunction with a non-radioactive polymerase
      chain reaction-high performance ion-exchange chromatographic (PCR/HPIEX) method,
      for the quantitative assessment of gene copy number in human biopsy samples. In
      particular, these methods have been established for the assessment of gene
      amplification with the FGF-2, FGF-3, FGF-4 and c-erb-B2 genes with the a single
      copy IFN-gamma gene used as an internal control. In principle, the same
      procedures could, in general, be simultaneously applied for monitoring the
      amplification or deletion of other oncogenes as well as normal genes in mammalian
      cells. Procedures to optimise the precision of the analysis have been examined,
      including the influence of the oligonucleotide primer concentrations, cycle
      number, extension temperature, and method of pre-treatment of the tissue sample
      with proteinase K. The results confirm that crude tissue lysates, rather than
      purified DNA samples, can be reliably employed, thus extending the scope of non
      radioactive PCR/HPIEX methods for the assessment of aberrant gene copy number to
      biological samples such as tumour biopsy tissues.

PMID- 9029266
TI  - Application of an optimised reverse transcriptase-polymerase chain reaction
      method to determine the cDNA nucleotide sequence of porcine basic fibroblast
      growth factor.
AB  - In the present investigation, oligonucleotide primers of high hybridisation
      stringency have been used in combination with optimised reverse transcriptase
      polymerase chain reaction (RT-PCR) methods for the determination of the cDNA
      sequence corresponding to porcine FGF-2 mRNA present in brain and uterine tissue.
      Application of these optimised methods have overcome previous limitations
      associated with the low abundance of the porcine FGF-2 mRNA, and allowed as
      little as 100 micrograms of tissue to be employed to generate the complete cDNA
      nucleotide sequences as well as to provide specific template fragments selected
      for their suitability in subsequent ligation and mutagenesis studies with
      conventional expression vectors. Comparisons of the cDNA nucleotide and the
      deduced amino-acid sequence of porcine FGF-2 and the known FGF-2s from other
      species have indicated nucleotide sequence homologies of 95.5% with the bovine,
      94.7% with the human and 88.7% with the rat FGF-2 cDNA whilst amino-acid sequence
      homologies of 100% with the bovine, 98.7% with the human and 96.8% with the rat
      FGF-2, respectively, were found. Based on these investigations, application of
      analogous strategies and methods with low abundance mRNAs related to other
      members of this family of growth factors, as well as very low abundance mRNAs of
      other protein growth factor, in the pig should now be readily realised.

PMID- 9029267
TI  - Fluorometric study of the isoform difference of mammalian metallothionein.
AB  - A fluorometric method for studying the isoform difference of mammalian
      metallothionein (MT), which lacks aromatic amino-acid residues, is reported.
      Cadmium-induced rabbit and hedgehog liver MT exhibited a strong luminescence
      signal in the range of 335 to 340 nm when excited at 285 nm in aqueous solution.
      The differences in emission intensity of the two major isoforms of MTs are
      significant. When titrated with chloride acid, which is believed to proton the
      metal-thiolate coordination bound to the -SH group in MT, a 10-nm red-shift
      property of the emission spectrum was observed, and the red-shift properties of
      the isoforms varied with the species. The observed fluorescence property of MT
      was considered to be the result of its polypeptide chains, which was confirmed by
      comparing the luminescence and absorption spectra during the titration of MT with
      diethylenetriaminepentaacetic acid. The new luminescence property of MT should be
      useful in studying the isoform and function difference of MT.

PMID- 9029268
TI  - Induction of liver cytochrome P-450 (CYP) 3A in male and female rats by a
      steroidal androgen receptor antagonist, zanoterone.
AB  - The cytochrome P-450 (CYP) mediated hydroxylation of testosterone to 6 beta-, 7
      alpha-, and 16 alpha-hydroxytestosterone (b beta-, 7 alpha-, and 16 alpha-OHT)
      and the dealkylation of ethoxycoumarin to 7-hydroxycoumarin (ECOD) and
      ethoxyresorufin to resorufin (EROD) were used to probe changes in CYP
      monooxygenase activities in liver microsomes from rats treated with the androgen
      receptor antagonist, zanoterone (Z). Phenobarbital (PB) and beta-naphthoflavone
      (beta-NF) were used as comparators. There were sex-related differences in the
      constitutive CYP activities and in the responses of CYP activities to Z. The
      greatest effect of Z administration was on 6 beta-OHT activity: It was increased
      up to 5.2-fold in males and 13.9-fold in females (Z high dose). The effect was
      larger than the produced by PB or beta-NF (< or = threefold increases). Z (high
      dose), PB, and beta-NF increased ECOD to a similar extent, e.g., about 1.3-fold
      in males and 1.2-2.9-fold in females. beta-NF increased EROD (11.2-fold males,
      6.2-fold females) more than PB (3.4- to 4.6-fold) or Z (1.3- to 1.7-fold). Since
      hydroxylation of testosterone at the 6 beta position in rats and humans is
      catalyzed primarily by CYP isoforms from the 3A subfamily, the increase in 6 beta
      OHT suggests that Z induced CYP 3A activity. These findings were confirmed with
      Western immunoblots with probes for rat CYP 1A1, 2B1/2, 2E1, 3A, and 4A. Z
      produced a three-to fourfold increase in the 3A isoform for both male and female
      rats. Results from this study suggest that in a clinical setting, Z therapy has
      the potential to induce CYPs of the 3A subfamily and in so doing alter the
      metabolism and clearance of drugs that are substrates for the 3A subfamily.

PMID- 9029269
TI  - Characterization of glutamate toxicity in cultured rat cerebellar granule neurons
      at reduced temperature.
AB  - We have defined conditions whereby glutamate becomes toxic to isolated cerebellar
      granule neurons in a physiologic salt solution (pH 7.4). In the presence of a
      physiologic Mg++ concentration, acute glutamate excitotoxicity manifests only
      when the temperature was reduced from 37 degrees C to 22 degrees C. In contrast
      to glutamate, N-methyl-D-aspartate (NMDA) was nontoxic at either temperature at
      concentrations as high as 1 mM. Glycine strongly potentiated both the potency and
      efficacy of glutamate but revealed only a modest NMDA response. The non-NMDA
      receptor antagonist, 6-cyano-7-nitroquinoxalinedione (CNQX), potently protected
      against glutamate challenge, although the contribution of antagonism at
      strychnine-insensitive glycine sites could not be excluded. To further
      characterize the non-NMDA receptor contribution to the excitotoxic response, the
      promiscuity of glutamate interaction with ionotropic receptors was simulated by
      exposing neurons to NMDA in the presence of non-NMDA receptor agonists. NMDA
      toxicity was potentiated four- to sevenfold when non-NMDA receptors were
      coactivated by a subtoxic concentration of AMPA, kainate, or domoate. These
      results suggest that non-NMDA receptor activation participates in the mechanism
      of acute glutamate toxicity by producing neuronal depolarization (via sodium
      influx), which in turn promotes the release of the voltage-dependent magnesium
      blockade of NMDA receptor ion channels.

PMID- 9029270
TI  - Alterations of the glutathione redox cycle status in fumonisin B1-treated pig
      kidney cells.
AB  - Fumonisin B1 (FB1) causes equine leukoencephalomalacia, porcine pulmonary edema,
      and liver tumors and chronic nephritis in rats. To investigate mechanisms by
      which FB1 induces toxicity, effects of FB1 on cellular glutathione (GSH) redox
      status and GSH depletion on FB1 toxicity in pig kidney (LLC-PK1) cells were
      studied. Treatment of LLC-PK1 cells with 50 microM FB1 for 24 hours significantly
      decreased cellular GSH contents from 56 +/- 3.2 to 42.7 +/- 4.4 nmol/mg protein
      (p < 0.05) and increased the activities of glutathione reductase (GR) from 25.7
      +/- 2.4 to 35.7 +/- 5.0 mumol NADPH/mg protein (p < 0.05). The activities of
      glutathione peroxidase (GSHpx), catalase, and Cu,Zn-superoxide dismutase (SOD)
      were not changed by this treatment. Treatment of LLC-PK1 cells for 12 hours with
      0.1 mM buthionine sulfoximine (BSO), a selective inhibitor of the enzyme gamma
      glutamylcysteine synthetase that catalyzes the rate-limiting reaction in de novo
      GSH synthesis, decreased cellular GSH levels to about 20% of that found in the
      control cells. The cells pretreated with 0.1 mM BSO for 12 hours were
      significantly sensitized to the FB1 cytotoxicity as determined by a long-term
      survival assay (p < 0.05). The results demonstrate that FB1 changes GSH redox
      cycle status in LLC-PK1 cells, and GSH may play a role in cytoprotection against
      FB1 toxicity.

PMID- 9029272
TI  - Blood antioxidant status and urine sulfate and thiocyanate levels in smokers.
AB  - Erythrocyte and plasma antioxidant enzyme activities and antioxidants as well as
      concentrations of total sulfate and thiocyanate were estimated in a group of
      healthy subjects and three groups of smokers (cigarette smokers, mixed tobacco
      smokers, and miscellaneous tobacco smokers). Plasma vitamin E, uric acid,
      ascorbic acid, ceruloplasmin, and urinary total sulfate concentrations were
      decreased, whereas dehydroascorbate and urinary thiocyanate concentrations were
      elevated in the three groups of smokers in comparison to the corresponding levels
      of the control subjects. On the other hand, erythrocyte superoxide dismutase and
      catalase as well as plasma superoxide dismutase activities were elevated in
      subjects of the three groups of smokers compared with the corresponding activity
      in subjects of the control group. Plasma catalase activity is statistically
      unaffected by smoking, but blood glutathione peroxidase activities were decreased
      in the three groups of smokers in comparison with the corresponding levels of the
      control group. There were also statistically meaningful differences between mean
      values of the antioxidant concentrations and the activities of the antioxidant
      enzymes in most of the smokers groups.

PMID- 9029273
TI  - Study of oxidative stress in isoniazid-induced hepatic injury in young rats with
      and without protein-energy malnutrition.
AB  - The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid
      (INH) was investigated in young growing rats. The interaction of moderate and
      severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic
      injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed
      kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin
      (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive
      fat globules could be demonstrated in frozen sections stained with oil red O'.
      The concomitant elevation of serum ALT/AST added support to the histopathologic
      injury. Electronmicroscopic analysis revealed the proliferation of rough
      endoplasmic reticulum in INH-treated groups. The glutathione and related thiols
      were decreased significantly by INH both in blood and liver tissues, indicating a
      decrease in protective mechanism. Glutathione reductase activity was elevated
      concomitantly in both the tissues. A significant decrease in the activity of
      glutathione peroxidase and catalase is again indicative of diminished capacity to
      handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these
      alterations indicated that the damage to the liver cell could well be operating
      through the inefficient disposal of superoxides (O-2) and H2O2. A profound
      decrease in the protective mechanism further aggravated the picture in moderate
      and severe PEM, which was observed with INH alone.

PMID- 9029271
TI  - Inhibition of mitochondrial function in isolated rate liver mitochondria by azole
      antifungals.
AB  - Ketoconazole is an imidazole oral antifungal agent with a broad spectrum of
      activity. Ketoconazole has been reported to cause liver damage, but the mechanism
      is unknown. However, ketoconazole and a related rug, miconazole, have been shown
      to have inhibitory effects on oxidative phosphorylation in fungi. Fluconazole,
      another orally administered antifungal azole, has also been reported to cause
      liver damage despite its supposedly low toxicity profile. The primary objective
      of this study was to evaluate the metabolic integrity of adult rat liver
      mitochondria after exposure to ketoconazole, miconazole, fluconazole, and the
      deacetylated metabolite of ketoconazole by measuring ADP-dependent oxygen uptake
      polarographically and succinate dehydrogenase activity spectrophotometrically.
      Ketoconazole, N-deacetyl ketoconazole, and miconazole inhibited glutamate-malate
      oxidation in a dose-dependent manner such that the 50% inhibitory concentration
      (I50) was 32,300, and 110 microM, respectively. In addition, the effect of
      ketoconazole, miconazole, and fluconazole on phosphorylation coupled to the
      oxidation of pyruvate/malate, ornithine/malate, arginine/malate, and succinate
      was evaluated. The results demonstrated that ketoconazole and miconazole produced
      a dose-dependent inhibition of NADH oxidase in which ketoconazole was the most
      potent inhibitor. Fluconazole had minimal inhibitory effects on NADH oxidase and
      succinate dehydrogenase, whereas higher concentrations of ketoconazole were
      required to inhibit the activity of succinate dehydrogenase. N-deacetylated
      ketoconazole inhibited succinate dehydrogenase with an I50 of 350 microM. In
      addition, the reduction of ferricyanide by succinate catalyzed by succinate
      dehydrogenase demonstrated that ketoconazole caused a dose-dependent inhibition
      of succinate activity (I50 of 74 microM). In summary, ketoconazole appears to be
      the more potent mitochondrial inhibitor of the azoles studied; complex I of the
      respiratory chain is the apparent target of the drug's action.

PMID- 9029292
TI  - A comparison of the inflammatory potential of particulates derived from two
      composite materials.
AB  - In order to develop total joint prostheses with moduli of elasticity close to
      bone while retaining excellent strength characteristics, composite materials are
      being developed. Composites consist of graphite fibers embedded in a polymer
      matrix. We studied the inflammatory potential of particulates derived from two
      composites with different matrix components, polysulfone (PFS) and
      polyetherketoneketone (PEKK), in the rat subcutaneous air pouch model. Neat
      components of the composites were studied separately in the air pouch.
      Particulates also were studied in culture using the macrophage cell line RAW
      264.7, adherent synovial cells (ASC), and human polymorphonuclear neutrophils
      (PMNs). Particles derived from the PEKK-containing composite material
      consistently were less inflammatory than the PFS composite-derived particles, as
      measured by PMN infiltration, neutral metalloprotease activity, tumor necrosis
      factor (TNF) activity, and prostaglandin E2 (PGE2) accumulation. Results from the
      neat materials confirmed the findings in the composite-derived material. PEKK
      composite-derived material produced less TNF from macrophage cultures, but there
      were no significant differences noted in PGE2 production from ASC or in
      superoxide anion generation from PMNs. Particles from both PSF and PEKK produced
      minimal inflammatory responses in the rat subcutaneous air pouch. PEKK elicited a
      response virtually the same as the saline control and significantly less than
      that produced by particles of PSF.

PMID- 9029274
TI  - Evaluation of reactive oxygen species involvement in amiodarone pulmonary
      toxicity in vivo and in vitro.
AB  - Amiodarone (AM) is an effective antidysrhythmic agent, restricted in use by the
      development of adverse effects, including potentially fatal AM-induced pulmonary
      toxicity (AIPT). Although the pathogenesis of AIPT is unknown, an oxidant
      mechanism has been proposed. The present study evaluated the role of reactive
      oxygen species (ROS) in AM-induced toxicity. The effect of inhibiting lung
      antioxidant defense on in vivo development of AIPT was evaluated in hamsters.
      Lung glutathione reductase activity was inhibited by 66%, 6 hours following
      administration of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (20 mg/kg i.p.).
      When AM (1.83 mumol) was administered intratracheally 6 hours after BCNU,
      toxicity was enhanced, as indicated by lung hydroxyproline content and
      histological evaluation 21 days later. However, BCNU treatment did not affect AM
      induced alterations in lung glutathione, suggesting that the increased toxicity
      was not due to decreased antioxidant capacity following BCNU. The effect of BCNU
      on AM cytotoxicity in vitro was evaluated using rabbit lung alveolar macrophages.
      Incubation with 5 microM BCNU for 2 hours caused greater than 95% inhibition of
      glutathione reductase activity. However, BCNU treatment had no effect on 146
      microM AM-induced cytotoxicity, as assessed by lactate dehydrogenase latency
      following 12 hours of incubation. Rabbit macrophages loaded with 2',7'
      dichlorofluorescein, which is oxidized by ROS to fluorescent 2',7'
      dichlorofluorescein (DCF), were used to evaluate ROS generation by AM. Incubation
      of macrophages with AM (73 or 146 microM) for 1 hour, with or without the
      catalase inhibitor sodium azide (1 mM), did not result in DCF formation. Overall,
      these results do not support the hypothesis that AIPT is due to ROS action.

PMID- 9029293
TI  - Fatigue behavior of zirconia hip joint heads: experimental results and finite
      element analysis.
AB  - Crack propagation in a commercial surgical grade zirconia ceramic was performed
      under static and cyclic loading. The slow crack growth (SCG) parameters were
      determined in both cases. The results reveal the existence of threshold values of
      applied stress intensity factor, for both static and cyclic loadings, below which
      no slow crack growth occurs. Such threshold values represent one of the best
      advantages of the present zirconia ceramic compared with other ceramic materials
      used in orthopedics, which could lead to a strong enhancement of implant
      lifetime. This threshold value was also identified by cyclic fatigue tests
      performed on zirconia femoral heads. From a new statistical approach based on the
      Monte Carlo method, the knowledge of SCG behavior, and the help of finite element
      analysis, an estimate of the lifetime prediction has been made and discussed.

PMID- 9029294
TI  - Relationship between microstructure and ductility of investment cast ASTM F-75
      implant alloy.
AB  - Hip replacement implants fabricated using the ASTM F-75 alloy sometimes fail in a
      sudden catastrophic way. In general, fractures start at microstructural defects
      subjected to stress-corrosion under chemical attack by body fluids. In this paper
      the results of a study on the effect of casting parameters on the microstructure
      of ASTM F-75 are presented. The preheating mold temperature and the liquid
      temperature were varied between 900 and 1000 degrees C, and 1410 and 1470 degrees
      C, respectively. Optimum static strength and ductility were obtained when
      shrinkage microporosity and the volume fraction of M23C6 "eutectic" carbides
      precipitated at grain boundaries were minimized by increasing the preheating mold
      temperature to 1000 degrees C and by using intermediate pouring temperatures of
      1455 degrees C. Under these casting conditions, however, the solidification rates
      are low, leading to large grain sizes, which, in turn, reduce the strength of the
      material under dynamic loading conditions. The volume fraction of the M23C6
      "blocky" carbides appears to be independent of the casting conditions; however,
      their size and spatial distributions determine the strength of the as-cast
      alloys.

PMID- 9029296
TI  - Enhanced strength in cemented stem fixation using adhesive acrylic cement as a
      metal coating material.
AB  - One cause of aseptic loosening of cemented total hip arthroplasty is mechanical
      weakness at the interface between the metal stem and the cured bone cement.
      Adhesive acrylic bone cement containing 4-methacryloyloxyethyl trimellitate
      anhydride (4-META) was applied as a metal coating material to increase the
      strength of the cemented fixation. The 4-META cement has 2-3 times greater
      tensile bond strength to metals than does commercial acrylic bone cement. The
      shear strength of the coated metals fixed with bone cement was approximately 4
      times greater in SUS-304 and 3 times greater in titanium (Ti) alloy than those of
      uncoated metals, and this strength did not decrease after 1 week's immersion in
      saline. The coating process using the 4-META cement can be performed at normal
      room temperature, so that metal stems for bone cement fixation could be coated
      during the course of an operation resulting in potentially improved results of
      total hip arthroplasty.

PMID- 9029295
TI  - Apatite as carrier for growth hormone: in vitro characterization of loading and
      release.
AB  - Previous studies concerning bone drug delivery systems have provided little data
      about the amount of drug loaded, one of the essential factors for determining the
      dose/effect relationship. To investigate this factor, an adsorption method
      involving a therapeutic agent was tested in vitro on an apatitic calcium
      phosphate (AP). One milligram of human growth hormone (hGH) was deposited onto
      0.1, 0.15, and 0.2 g of AP powder over a period of 24 h at 37 degrees C. The
      amount of hGH loaded was determined by subtracting the dose recovered from that
      applied on AP. The results show that 1 g of AP absorbed 9.48 mg of hGH. From 0.1
      and 0.15 g of hGH-loaded AP, hGH was released in vitro for 2 and 3 weeks,
      respectively, with a 50% time release (T1/2) at 30 h and 72 h, respectively, for
      the two quantities. The amount of drug loaded and the determined release kinetics
      were compatible with the action pattern of hGH, indicating that hGH-loaded
      calcium phosphate supports are suitable for bone-growth promotion.

PMID- 9029297
TI  - Three-dimensional examination of bone structure around hydroxyapatite implants
      using digital image processing.
AB  - This study introduced a new method for three-dimensional (3D) examination of the
      bone structure around an implant and presented 3D bone-implant contact rates. A
      block of nondecalcified implant tissue was ground gradually at an interval of 80
      micrograms for the collection of serial two-dimensional (2D) images. An image of
      the stained block surface was instantly recorded by a charge-couple device (CCD)
      camera and computer-aided system. A 3D model was reconstructed from 60-70 sheets
      of serial 2D images. The 3D bone structure around the implant was shown in
      perspective and displayed all sides of the implant. The bone-implant contact rate
      depended on the cutting position and direction in the specimen. The 3D model will
      be necessary and valuable for the biomechanical study of dynamic bone changes
      around implants.

PMID- 9029298
TI  - New radiopaque polyHEMA-based hydrogel particles.
AB  - New iodine-containing polymeric hydrogel particles were prepared by suspension
      radical copolymerization of 2-hydroxyethyl methacrylate (HEMA), 3
      (methacryloylamidoacetamido)-2,4,6-triiodobenzoic acid (MABA) and ethylene
      dimethacrylate (EDMA) in an aqueous medium using azobisisobutyronitrile as an
      initiator and magnesium hydroxide as a suspension stabilizer. To impart porosity
      to the product, cyclohexanol and 1-dodecanol were added as inert diluents to the
      polymerization mixture. Particles containing 27 wt % iodine produced radiopacity
      sufficient to observe a clearly visible X-ray image. The equilibrium swelling
      behavior of the particles in water was characterized. Swelling of the particles
      dramatically increased by converting the acid groups of MABA into their Na+ form.
      The more MABA the copolymer particle contain, the higher is their swelling in the
      Na+ form.

PMID- 9029299
TI  - Controlling cell interactions by micropatterning in co-cultures: hepatocytes and
      3T3 fibroblasts.
AB  - The repair or replacement of damaged tissues using in vitro strategies has
      focused on manipulation of the cell environment by modulation of cell
      extracellular matrix interactions, cell-cell interactions, or soluble stimuli.
      Many of these environmental influences are easily controlled using macroscopic
      techniques; however, in co-culture systems with two or more cell types, cell-cell
      interactions have been difficult to manipulate precisely using similar methods.
      Although microfabrication has been widely utilized for the spatial control of
      cells in culture, these methods have never been adapted to the simultaneous co
      cultivation of more than one cell type. We have developed a versatile technique
      for micropatterning of two different cell types based on existing strategies for
      surface modification with aminosilanes linked to biomolecules and the
      manipulation of serum content of cell culture media. This co-culture technique
      allowed manipulation of the initial cellular microenvironment without variation
      of cell number. Specifically, we were able to control the level of homotypic
      interaction in cultures of a single cell type and the degree of heterotypic
      contact in co-cultures over a wide range. This methodology has potential
      applications in tissue engineering, implant biology, and developmental biology,
      both in the arena of basic science and optimization of function for technological
      applications.

PMID- 9029300
TI  - Adhesion to silicone rubber of yeasts and bacteria isolated from voice
      prostheses: influence of salivary conditioning films.
AB  - Adhesion of yeasts and bacteria to silicone rubber is one of the first steps in
      the biodeterioration of silicone rubber voice prostheses. In this paper, adhesion
      of two streptococcal, staphylococcal, Candida albicans and Candida tropicalis
      strains, isolated from explanted voice prostheses was investigated to silicone
      rubber with and without a salivary conditioning film in a parallel-plate flow
      chamber. Within each microbial pair of one species, the strain with the most
      negative zeta potential adhered most slowly to negatively charged silicone
      rubber. No other clear relationships were obvious between adhesion to silicone
      rubber and microbial zeta potentials of cell-surface hydrophobicities, as by
      water contact angles. A 1.5-h adsorbed salivary conditioning film appeared to
      possess components, presumably albumin and lysozyme, slowing down the deposition
      of the yeasts and some of the streptococcal and staphylococcal isolates. In
      addition, microbial adhesion in a stationary end point was generally lower to
      silicone rubber with an adsorbed salivary conditioning film than without one.
      Nearly all microorganisms adhering to an adsorbed salivary conditioning film,
      yeasts as well as bacteria, were stimulated to detach by the passage of an air
      bubble through the chamber, but microorganisms adhering directly to the silicone
      rubber, especially C tropicalis strains, detached in far lower numbers under the
      influence of a passing air bubble. The present observations are in agreement with
      clinical in vivo findings that in patients with reduced saliva production after
      radiotherapy, the device life of the voice prosthesis is significantly shortened
      and suggests that isolated salivary components might be used as an anti-adhesive.

PMID- 9029301
TI  - Evaluation of matrix scaffolds for tissue engineering of articular cartilage
      grafts.
AB  - Injury to articular cartilage predisposes that joint to further degeneration and
      eventually osteoarthritis. Recent studies have demonstrated the feasibility of
      using chondrocytes together with different biomaterial carriers as grafts for the
      repair of cartilage defects. The following study was undertaken to determine the
      effect of a variety of these materials on chondrocyte growth and extracellular
      matrix synthesis. We cultured chondrocytes on several commonly used materials and
      compared their rates of synthesis of proteoglycan and collagen. Additionally, we
      evaluated them in a closed culture recirculating system on these materials and
      compared them with standard culture techniques. This was done to see whether such
      a bioreactor-type system can be used to enhance the quality of in vitro
      reconstructed tissues. Our results demonstrated marked variability with respect
      to how chondrocytes responded to culture on the various materials. Bioabsorbable
      polymers such as polyglycolic acid (PGA)--enhanced proteoglycan synthesis,
      whereas collagen matrices stimulated synthesis of collagen. The use of the closed
      culture system, in general, improved the rates of synthesis of collagen and
      proteoglycan on the different material scaffolds. Exceptions were collagen
      synthesis on collagen matrices: use of the closed culture system did not enhance
      the rate of synthesis. Rates of proteoglycan synthesis on PGA scaffold initially
      was higher in the closed culture system but did not sustain a difference over the
      entire course of the 3-week culture period. This study demonstrates the
      importance of carrier material for the purpose of cartilage tissue reconstruction
      in vitro.

PMID- 9029302
TI  - Effects of cement creep on stem subsidence and stresses in the cement mantle of a
      total hip replacement.
AB  - In cemented total hip prostheses, the role of creep of the acrylic cement
      (polymethyl methacrylate, [PMMA]) in increasing or decreasing the chance of
      failure of the cement mantle is a subject of ongoing controversy. In the present
      study we used a three-dimensional finite-element model of a cemented stem to
      assess the influence of cement creep on subsidence of the stem, and on the stress
      and strain in the cement under cyclic load, both in the short and long term. The
      cement layer was assigned the shear and bulk creep moduli of Zimmer regular PMMA
      cement, which were obtained experimentally. The stem-cement interface was modeled
      either as (1) completely bonded, (2) completely debonded with friction, or (3)
      completely debonded and frictionless. Under the cyclic load some cement creep
      occurred with all three bonding conditions, allowing additional subsidence of the
      stem and a decrease in the stress components within the cement. During the
      unloaded period the full recovery of the preload conditions could be reached with
      the completely bonded and with the frictionless interfaces. With the frictional
      interface there was residual cement creep, residual stresses within the cement,
      and residual subsidence of the stem during the unloaded period; however, the
      reduction of the stress was at most 13% and the subsidence was about 0.46 mm. The
      much larger subsidence of debonded stems that is often observed clinically might
      be attributed to the factors which were not included in the present model, such
      as circumferential bone remodeling.

PMID- 9029303
TI  - Effects of calcium phosphate bioceramics on skeletal muscle cells.
AB  - With advances in ceramics technology, calcium phosphate bioceramics have been
      applied as bone substitutes. The effects of implants on bony tissue have been
      investigated. The effects upon adjacent skeletal muscles have not been
      determined. The focus of this work is to elucidate the biological effects of
      various calcium phosphate bioceramics on skeletal muscles. Four different kinds
      of powder of calcium phosphate biomaterials including beta-tricalcium phosphate
      (beta-TCP), hydroxyapatite (HA), beta-dicalcium pyrophosphate (beta-DCP) and
      sintered beta-dicalcium pyrophosphate (SDCP), were tested by myoblast cell
      cultures. The results were analyzed by cell count, cell morphology and
      concentration of transforming growth factor beta 1 (TGF-beta 1) in culture
      medium. The cell population and TGF-beta 1 concentration of the control sample
      increased persistently as the time of culture increased. The changes in cell
      population and TGF-beta 1 concentration in culture medium of the beta-TCP and HA
      were quite low in the first 3 days of culture, then increased gradually toward
      the seventh day. The changes in cell population and TGF-beta 1 concentration in
      culture medium of the silica, beta-DCP, and SDCP were quite similar. They were
      lower during the first day of culture but increased and reached that of the
      control medium after 7 days' culture. Most cells on B-TCP and HA diminished in
      size with radially spread, long pseudopods. We conclude that HA and beta-TCP are
      thought to have an inhibitory effect on growth of the myoblasts. The HA and beta
      TCP may interfere with the repair and regeneration of injured skeletal muscle
      after orthopedic surgery.

PMID- 9029304
TI  - Physicochemical and biological studies of corona-treated artificial membranes
      used for pancreatic islets encapsulation: mechanism of diffusion and interface
      modification.
AB  - The artificial AN69 membrane (Hospal), a synthetic copolymer composed of
      acrylonitrile and sodium methallyl sulphonate suitable for pancreatic islet
      encapsulation, was submitted to physicochemical treatment (Corona discharge) to
      improve its insulin permeability. X-ray photoelectron spectroscopy (XPS) analysis
      of the AN69 membrane indicated the presence of up to two molecular layers of
      glycerol at its surface while the surface energies revealed the presence of
      hydrophilic sites (-SO3Na/glycerol) located at the membrane surface and
      acrylonitrile hydrophobic groups inside the material. The Corona discharges
      decreased the number of glycerol molecules at the membrane surface and from a
      biological point of view, produced a threefold increase in insulin diffusion.
      Furthermore, the biocompatibility of the treated membrane was preserved after 1
      year of intraperitoneal implantation. The increase in insulin permeability should
      result from a decrease of the membrane polarity and of a steric hindrance in
      pores. Thus, Corona discharge treatment may serve to optimize the properties of
      artificial membranes used for pancreatic islets encapsulation.

PMID- 9029305
TI  - In vitro growth of human adult bone-derived cells on hydroxyapatite plasma
      sprayed coatings.
AB  - The growth of adult human bone-derived cells on hydroxyapatite (HA) plasma
      sprayed coatings was investigated. Such cells were difficult to grow on original
      plasma-sprayed coatings, even following rinsing and rubbing down. We obtained
      cell growth only on samples previously immersed 15 or 22 days in complete culture
      medium. We describe a dissolution/precipitation phenomenon on the HA coating
      surface assessed by modifications of Ca and P concentrations in the culture
      medium, by the transformation of the HA coating into carbonated HA (X-ray
      diffraction and infrared spectrometry and by the presence demonstrated by
      scanning electron microscopy of spherocrystallites on the HA after 15 days of
      immersion. Our results show that adult human bone-derived cells are apparently
      particularly sensitive to the changes in the coating surface induced by liquid
      immersion. We raise the question of the limits of in vitro investigations on
      bioactive ceramics such as HA plasma-sprayed coatings susceptible to modification
      by simple immersion in aqueous solutions such as cell culture medium or
      physiologic saline.

PMID- 9029306
TI  - 2-hydroxyethyl methacrylate-terminated polyurethane/polyurethane interpenetrating
      polymer networks.
AB  - The interpenetrating polymer networks (INPs) of polyurethane (PU) and 2
      hydroxyethyl methacrylate (MEHA)-terminated polyurethane (HPU) were prepared by
      solution polymerization. PU prepolymer was synthesized from 4,4-diphenyl methane
      diisocyanate (MDI) and poly(propylene oxide) glycol (PPG). HPU prepolymer was
      synthesized from MDI, poly(tetramethylene oxide) glycol and HEMA. Dynamic
      mechanical analysis showed that the resultant IPN membranes have good
      compatibility between their constituents. As the HPU content increased, the
      tensile strength of the IPNs first increased and then decreased. For the highest
      tensile strength, the optimum HPU content was about 25 wt %. The value of surface
      tension of IPNs varied from 44.4 to 50.5 dyne/cm, and polarity ranged from 0.59
      to 0.91. The relative index of platelet adhesion (RIPA) of the IPN membranes was
      measured by the dynamic thrombosis test at constant shaking speed and
      temperature. By the criteria of this test, the IPN membranes with HPU content of
      about 25 wt% to the minimum platelet adhesion. When measured by the angular
      dependent ESCA technique on the surface of IPN samples, the variation in the RIPA
      correlated to the change in the surface soft segment to hard segment ratio.
      Higher HPU content resulted in more migration of soft segments toward the
      surface. The platelet adhesion was observed to be minimized when the surface O/N
      ratio was around 12.

PMID- 9029307
TI  - Bending strength of synthetic OH-carbonated hydroxyapatite single crystals.
AB  - Although hydroxyapatite (HAP) is applied to medical implants because of its
      biocompatibility, no data on mechanical strength of HAP single crystals were yet
      available, partly due to the difficulty in obtaining sufficiently large single
      crystals. In the present study the bending strength of OH-carbonated
      hydroxyapatite (CHAP) single crystals containing carbonate of 0.09 CO2 wt %
      prepared hydrothermally was determined in three-point bending tests. The three
      point bending tests were performed using a modified ultra micro-hardness tester
      with a span of 380 micrograms and a bending direction of <210>. The CHAP single
      crystals were broken in air, water, and air after immersion in alpha minimum
      essential medium (alpha MEM) + 10% fetal bovine serum (FBS) for 3 weeks. The
      average bending strength of the CHAP single crystals was 468 +/- 205, 361 +/- 199
      and 501 +/- 212 MPa in air, water, and air after immersion in alpha MEM + 10%
      FBS, respectively. In all cases the maximum strength at each crystal thickness
      value decreased in inverse proportion to the thickness.

PMID- 9029308
TI  - Sensitive, selective gas chromatographic-mass spectrometric analysis with
      trifluoroacetyl derivatives and a stable isotope for studying tissue sorbitol
      producing activity.
AB  - One of the major mechanisms involved in diabetic microangiopathy is considered to
      be an altered polyol pathway. However, clarifying the pathophysiology is
      difficult due to the lack of a sensitive method for measuring the reduction of
      glucose to sorbitol in tissue. Here we report a sensitive and selective method
      for polyol measurement using trifluoroacetyl (TFA) derivatives of polyols and
      stable isotope-labeled D-sorbitol (U-[13C]sorbitol, 13C6H14O6, 98.7%) as an
      internal standard. Gas chromatography-mass spectrometry (GC-MS) using an SE-30
      capillary column gave elution of TFA derivatives of sugars, polyols and U
      [13C]sorbitol within 8 min, with clear separation of sorbitol. In the calibration
      study, the coefficients of correlation between the amount of sorbitol added and
      that determined in standard solutions containing 0.1-8.0 nmol sorbitol,
      erythrocyte mixture and liver cytosol mixture were r = 0.999, r = 0.997 and r =
      0.997, respectively. The precision of the GC-MS measurement of standard solution
      was C.V. = 4.3%. Because glucose is used as a substrate, the method can clarify
      the polyol pathway under physiological conditions. With this method, Km and Vmax
      values of the reductase in erythrocytes were 115 +/- 19 mmol/l and 4.42 +/-
      nmol/min/g of hemoglobin. In human liver, on the other hand, they were 755 +/-
      132 mmol/l and 0.773 +/- 0.090 nmol/min/mg of protein, respectively. This
      difference of Km values suggested that aldehyde reductase rather than aldose
      reductase is mainly responsible for reducing glucose to sorbitol in the liver. In
      conclusion, this newly developed method offers a highly sensitive and selective
      procedure for measuring low concentrations of sorbitol in various tissues and
      cells and should enable clarification of the kinetics of glucose reduction to
      sorbitol, which in turn can be used to evaluate the role of an altered polyol
      pathway in the pathophysiology of diabetic microangiopathy.

PMID- 9029310
TI  - Rapid size-exclusion chromatography of proteoglycans.
AB  - The separation of intact proteoglycans using high-performance liquid
      chromatography is not trivial because the high molarity denaturing buffers
      required to maintain proteoglycans in the disaggregated state create back
      pressures higher than the limits of many HPLC systems. Until recently, low back
      pressure requirements of HPLC size-exclusion columns precluded their use for the
      separation of intact proteoglycans. In this study we show that rapid size
      exclusion chromatography is possible in 8 M urea buffers using a Dionex BioLC
      system equipped with a Bio-Rad BioSil Sec-400 column. This technique reduced the
      time required for size-exclusion chromatography of intact proteoglycans from
      approximately 18 h (Sepharose CL4B) to 25 min and in some cases improved
      resolution of the sample.

PMID- 9029311
TI  - Abnormal microheterogeneity detected in one commercial alpha 1-acid glycoprotein
      preparation using chromatography on immobilized metal affinity adsorbent and on
      hydroxyapatite.
AB  - The study of one commercial preparation of human alpha 1-acid glycoprotein (AAG)
      by isoelectric focusing and by different chromatographic methods, previously
      developed to purify and fractionate the genetic variants of AAG, revealed an
      abnormal heterogeneity for this preparation. In addition to the three main
      variants (F1, S and A) of AAG normally present, this preparation contained five
      other AAG variants (called here sigma, alpha, beta, delta and gamma), accounting
      for ca. 40% of the total. As it is very unlikely that the latter variants are
      rare AAG variants, the abnormal heterogeneity of this AAG preparation is most
      probably due to structural alterations occurring during the large scale
      isolation. The alpha and the sigma, beta, delta and gamma variants could
      correspond to altered forms of the A and the F1 and S variants, respectively,
      because of their similar retention behaviour on immobilized copper(II) ions and
      their similar drug binding properties. However, the elution of the variants from
      the immobilized metal affinity column suggested that sigma, alpha, beta, delta
      and gamma were desialylated. Chromatography on hydroxyapatite enabled the
      separation of the F1, S and A variants from the sigma, alpha, beta, delta and
      gamma variants. The inability of the latter variants to bind to hydroxyapatite
      suggests that the structural alterations might involve acidic amino acid
      residues. This proposal agreed with the isoelectric focusing study of variants
      sigma, alpha, beta, delta and gamma. Since the different separation methods used
      were able to resolve the variants of this AAG, this protocol could be used for
      characterization of commercial AAG proteins.

PMID- 9029309
TI  - Method for combined analysis of profiles of conjugated progesterone metabolites
      and bile acids in serum and urine of pregnant women.
AB  - A method for analysis of profiles of conjugated progesterone metabolites and bile
      acids in 10 ml of urine and 1-4 ml of serum from pregnant women is described.
      Total bile acids and neutral steroids from serum and urine were extracted with
      octadecylsilane-bonded silica. Groups of conjugates were separated on the
      lipophilic ion-exchanger triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20).
      Fractions were divided for steroid or bile acid analyses. Sequences of
      hydrolysis/solvolysis and separations on TEAP-LH-20 permitted separate analyses
      of steroid glucuronides, monosulfates and disulfates and bile acid aminoacyl
      amidates, sulfates, glucuronides and sulfate-glucuronides. Radiolabelled
      compounds were added at different steps to monitor recoveries and completeness of
      separation, and hydrolysis/solvolysis of conjugates was monitored by fast-atom
      bombardment mass spectrometry. The extraction and solvolysis of steroid
      disulfates in urine were studied in detail, and extraction recoveries were found
      to be pH-dependent. Following methylation of bile acids, all compounds were
      analysed by capillary gas chromatography and gas chromatography-mass spectrometry
      of their trimethylsilyl ether derivatives. Semiquantification of individual
      compounds in each profile by gas-liquid chromatography had a coefficient of
      variation of less than 30%. The total analysis required 3 days for serum and 4
      days for urine.

PMID- 9029312
TI  - High-performance liquid chromatographic determination of imidazole dipeptides,
      histidine, 1-methylhistidine and 3-methylhistidine in equine and camel muscle and
      individual muscle fibres.
AB  - The combined solid-phase extraction (Isolute PRS columns) and reversed-phase
      gradient HPLC method presented provides a sensitive, reproducible and selective
      quantification of carnosine, balenine, homocarnosine, histidine, 1
      methylhistidine and 3-methylhistidine in equine and camel muscle and individual
      muscle fibres. Recoveries were 91-115%. Lower limits of detection were 0.005
      0.010 mmol kg-1 dry muscle. The compounds were isolated from other physiological
      amino acids and small peptides and resolved within a single chromatographic run
      of 55 min. Concentrations of these compounds in equine myocardium, diaphragm,
      skeletal muscle, camel muscle and individual muscle fibres of both species are
      presented for the first time.

PMID- 9029313
TI  - Simultaneous determination of low plasma concentrations of retinol and
      tocopherols in preterm infants by a high-performance liquid chromatographic
      micromethod.
AB  - A method for the simultaneous determination of low concentrations of retinol and
      tocopherols from 100 microliters plasma using isocratic reversed-phase HPLC is
      described. Retinol is quantified with a programmable UV-Vis detector, whereas
      tocopherols are quantified by fluorescence detection using tocol as the internal
      standard. Intra- and inter-assay precision are 3.7 and 4.3% for retinol and 2.3
      and 6.1% for alpha-tocopherol, respectively. The accuracy as determined with
      standard material from the US National Institute of Standards and Technology with
      low, medium and high concentrations is in the range of 0.2-6.0% bias for retinol
      and of -3.0 to 5.5% for alpha-tocopherol, respectively. This method is highly
      sensitive and selective and has a good precision and accuracy for measuring low
      concentrations of vitamins in small plasma volumes.

PMID- 9029314
TI  - High-performance thin-layer chromatographic determination of N-ethyl-3,4
      methylenedioxyamphetamine and its major metabolites in urine and comparison with
      high-performance liquid chromatography.
AB  - The consumption of N-ethyl-3,4-methylenedioxyamphetamine (MDE, 1), an analogue of
      ecstasy, can be detected by direct in situ HPTLC-FTIR measurement of the main
      metabolite N-ethyl-4-hydroxy-3-methoxyamphetamine (HME, 2). HME (2) can, like the
      other important metabolite 3,4-methylenedioxyamphetamine (MDA, 3) and unchanged
      MDE (1), be determined quantitatively in urine by HPTLC-UV after two-step
      automatic development. The results have been compared with those obtained using
      an HPLC method. The differences were not generally significant. Small deviations
      were attributable to the different sample preparation methods necessary. The
      working range for the HPTLC method was between 0.1 and 8.2 micrograms/ml and for
      the HPLC method between 0.2 and 60.0 micrograms/ml. The method standard
      deviations were 2.66-4.91% (HPTLC) and 0.48-3.67% (HPLC).

PMID- 9029315
TI  - Micellar electrokinetic chromatography as a fast screening method for the
      determination of the doping agents furosemide and piretanide in urine.
AB  - The possibility of using micellar electrokinetic chromatography for the screening
      of the loop diuretics piretanide and furosemide in urine was studied. A fast and
      simple method with good repeatability is described. The method was applied to
      urine samples collected from a healthy volunteer after oral administration of
      therapeutic doses of each compound. Positive identification in the urine matrix
      was possible through recording diode array spectra.

PMID- 9029316
TI  - Determination of subnanogram concentrations of fentanyl in plasma by gas
      chromatography-mass spectrometry: comparison with standard radioimmunoassay.
AB  - A method was devised to determine fentanyl plasma concentrations by GC-MS using
      selected-ion monitoring (SIM) with sufentanil as internal standard. This was
      compared with a commonly used commercial radioimmunoassay (RIA). Sample
      preparation for GC-MS involved basification of plasma then extraction using n
      butyl chloride followed by concentration to dryness and reconstitution in toluene
      for chromatography. Using 1-ml plasma samples, the estimated limit of detection
      of fentanyl was 20 pg/ml. Blood samples for pharmacokinetic studies were split
      and assayed by GC-MS and RIA which had a limit of detection of 200 pg/ml.
      Pearson's r (r - 0.80, p < 0.0001) indicated the methods were highly correlated
      at all plasma concentrations. Owing to the greater sensitivity of the method, GC
      MS is recommended over RIA for subnanogram determination of fentanyl in plasma.

PMID- 9029317
TI  - Simultaneous gas chromatographic-mass spectrophotometric determination of alpha
      fluoro-beta-alanine and 5-fluorouracil in plasma.
AB  - A gas chromatographic-mass spectrometric (GC-MS) method is reported for
      simultaneous determination of alpha-fluoro-beta-alanine (FBA), the major end
      metabolite of 5-fluorouracil (5-FU), and 5-FU in plasma samples isolated from
      cancer patients. 5-Chlorouracil (5-CIU, 1 micrograms/ml) is added to samples as
      an internal standard. The method relies on protein precipitation of the plasma
      sample followed by derivatisation with pentafluorobenzyl bromide. Following
      sample purification with Sep-pak C18 columns the derivatives are analysed by GC
      MS, with FBA, 5-FU and 5-CIU being determined at 36.96-37.03, 46.91-46.98 and
      51.99-52.13 min, respectively. The ions measured in each case had m/z of 390, 490
      and 506, respectively. The method showed good reproducibility with coefficients
      of variation between 3 and 10%, with a detection limit of < 1 ng/ml for 5-FU and
      < 5 ng FBA/ml plasma. The possibility of sensitive determination of FBA without
      the use of radioisotopes should permit routine estimation of rates of 5-FU
      metabolism in individual patients.

PMID- 9029318
TI  - Determination of a new carbapenem derivative, DA-1131, in plasma and urine by
      high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method was developed for the
      determination of a new carbapenem, DA-1131 (I), in human plasma and urine and in
      rat blood and tissue homogenates. The method involved deproteinization of the
      biological samples with 1 volume each of 0.04 M Ba(OH)2 and ZnSO4 aqueous
      solution. A 50-microliters aliquot of the supernatant was injected onto a C18
      reversed-phase column. The mobile phase employed was 0.015 M KH2PO4-acetonitrile
      (9:1, v/v) with a pH of 5.0. The flow-rate was 0.8 ml/min. The column effluent
      was monitored by a ultraviolet detector at 300 nm. The retention time of I was
      8.0 min. The detection limits of I in human plasma and urine were 0.1 and 0.5
      micrograms/ml, respectively. The coefficients of variation of the assay were
      generally low (below 8.39%) for human plasma and urine, and rat blood and tissue
      homogenates. No interferences from endogenous substances were observed.

PMID- 9029319
TI  - Determination of angiotensin II receptor antagonist (E4177) in human plasma and
      urine by high-performance liquid chromatography.
AB  - A sensitive reversed-phase high-performance liquid chromatographic (HPLC) method
      with fluorescence detection was developed for the analysis of a new angiotensin
      II receptor antagonist, E4177, in human plasma and urine. The analyte and
      internal standard (I.S.) are extracted from acidified plasma and urine by liquid
      liquid extraction and then refined by solid-phase extraction. The extraction
      recovery was greater than 90%. E4177 and I.S. were separated from endogenous
      components in plasma and urine on a C18 column using a mobile phase of
      acetonitrile-water-85% phosphoric acid (27.3:72.0:0.7, v/v). The eluent was
      monitored by fluorescence with excitation and emission set at 280 and 380 nm,
      respectively. The assay was linear from 2.5 to 1000 ng/ml of plasma and from 5 to
      1500 ng/ml of urine. The limit of quantification was 2.5 and 5 ng/ml for plasma
      and urine, respectively. Inter- and intra-day coefficients of variation for the
      plasma and urine ranged from 0.6 to 4.7%. E4177 was stable in plasma and urine
      for at least 9 months during storage at -20 degrees C, respectively. The method
      was successfully applied to the determination of E4177 in plasma and urine for a
      pharmacokinetic study.

PMID- 9029320
TI  - Determination of ebrotidine and its metabolites in human urine by reversed-phase
      ion-pair high-performance liquid chromatography.
AB  - Ebrotidine is a new H2-receptor antagonist with powerful antisecretory activity,
      demonstrated gastroprotection and the ability to inhibit protease and lipase
      activities of Helicobacter pylori. As a tool in the clinical pharmacokinetic
      study of ebrotidine, an analytical method for the simultaneous determination of
      ebrotidine an its metabolites in human urine was developed. An ion-pair reversed
      phase HPLC separation using 1-hexanesulfonic acid and acetonitrile as mobile
      phase with gradient elution was optimized. In addition, several procedures of
      preconcentration and clean-up were tested, including solid-phase and liquid
      liquid extraction, the mixture dichloromethane-2-propanol (9:1, v/v) at pH 11
      being the most efficient. The quality parameters of the whole analytical method
      were established, the calibration curves were linear over the range studied (1
      200 micrograms/ml) and the reproducibility of the method was high (inter-day
      R.S.D. values lower than 4.4%). The limits of detection were between 26 and 110
      ng/ml of urine for ebrotidine and its metabolites. The method was applied to the
      analysis of urine collected from two volunteers during 96 h following oral
      administration of ebrotidine at a dose of 400 mg.

PMID- 9029321
TI  - Determination of turosteride, a new inhibitor of 5 alpha-reductase, in human
      plasma by high-performance liquid chromatography with ultraviolet detection.
AB  - A sensitive and specific HPLC method for the determination of turosteride in
      human plasma was developed and validated. Turosteride was extracted from plasma
      with diethyl ether. Further purifications of the fraction extracted were
      performed sequentially by solid-phase extraction using a CN cartridge and by
      liquid-liquid partition between n-hexane and acetonitrile. Finally the
      acetonitrile solution containing the test compound was evaporated to dryness and
      the residue dissolved in the mobile phase, then injected onto the HPLC system.
      The chromatographic separation was performed isocratically by a reversed-phase
      column filled with ODS using a water-acetonitrile-methanol mixture. The eluate
      was monitored at 210 nm. No peak interfering with that of turosteride was
      observed when blank human plasma was assayed. Linearity was obtained in the
      turosteride concentration range of 5-1000 ng/ml plasma. Six calibration curves in
      plasma prepared and run on six different days showed correlation coefficients
      higher than 0.99 and good reproducibility of the slope (C.V. = 4.3%). The intra
      day precision, evaluated at three concentrations (in the low, mid and high range
      of the standard curve) and expressed as C.V., ranged from 0.81 to 13.25%. The
      inter-day precision evaluated at the same concentrations was better than 10.7%.
      The inter-day accuracy evaluated in the same samples and expressed as the ratio
      of found/added amount of turosteride ranged from 97.66 to 98.38%. The limit of
      quantitation was 5 ng/ml plasma. The HPLC method described was successfully
      employed for the determination of turosteride in plasma samples obtained during a
      phase I clinical trial with the test compound.

PMID- 9029322
TI  - Determination of a basic drug, bambuterol, in human plasma by capillary
      electrophoresis using double stacking for large volume injection and supported
      liquid membranes for sample pretreatment.
AB  - In this work we show the potential of using a double stacking procedure based on
      field enhancement as a means to increase the concentration sensitivity in CZE
      analysis of human plasma extracted by the supported liquid membrane (SLM)
      technique. A basic drug, bambuterol, was used as a model substance. The low ionic
      strength of the SLM extract makes this pretreatment technique compatible with the
      double stacking sequence. No significant loss of separation performance was
      observed when 3 microliters of SLM extract was concentrated by the CZE double
      stacking sequence. Almost no visible difference was seen between the
      electropherograms after enrichment of a plasma blank and an aqueous blank. Good
      performance of the whole procedure was demonstrated and detection limits in the
      low nM range were obtained in spite of the relatively weak UV absorbance of
      bambuterol. The developed procedure was evaluated for both achiral and chiral
      separation. In the latter approach chiral selectivity was obtained by adding
      cyclodextrin to the separation electrolyte.

PMID- 9029323
TI  - Determination of pentamidine in serum and urine by micellar electrokinetic
      chromatography.
AB  - A number of parameters influencing the electrokinetic processing of pentamidine
      by micellar electrokinetic chromatography (MEKC) were studied in order to develop
      an analytical method for this compound. The parameters considered were: pH, ionic
      strength, and SDS concentration of electrolyte, temperature and working voltage.
      On the basis of the results obtained, the best analytical conditions for the
      detection of pentamidine in serum and urine by MEKC were determined. Analysis by
      MEKC permitted determination of the drug in 10 min. Good linearity,
      reproducibility and accuracy were obtained in the range 0-30 micrograms/ml for
      both samples, with a correlation coefficient r > or = 0.9998 and a recovery of 87
      92% in serum and 90-108.9% in urine. We examined the metabolism of pentamidine
      using rat liver homogenates in order to exclude any possible interference of
      metabolites in the analysis of pentamidine.

PMID- 9029324
TI  - Identification and quantitation of iodotyrosines and iodothyronines in proteins
      using high-performance liquid chromatography by photodiode-array ultraviolet
      visible detection.
AB  - We describe a new method for the separation, identification and quantitation of
      iodotyrosines and iodothyronines [3-monoiodo-L-tyrosine (MIT), 3,5-diiodo-L
      tyrosine (DIT), L-thyronine (T0), 3,5-diiodo-L-thyronine (T2), 3,5,3'-triiodo-L
      thyronine (T3), reverse 3,3',5'-triiodo-L-thyronine (rT3) and 3,3',5,5'-tetraiodo
      L-thyronine (T4)]. Reversed-phase high-performance liquid chromatography (RP
      HPLC) was performed on a Nucleosil C8 column with photodiode-array UV-Vis
      detection. A clearly defined elution profile was obtained of each iodoamino acid
      (iodotyrosines and iodothyronines) using a linear gradient from 20 to 80% phase B
      (90% acetonitrile, 10% water, 0.1% TFA), phase A (water, 0.1% TFA, pH 2.0) eluted
      over 40 min. Iodoamino acid composition was determined, taking into account
      retention times and spectral characteristics. Thyroid protein samples were
      digested enzymatically and the complex mixture of IAA was then injected onto the
      RP-HPLC system. A photodiode-array detector with a dynamic range in the UV-Vis
      region was used in the HPLC system to monitor the absorbance at different
      wavelengths continuously, collecting data which were compared with standard
      samples. Each IAA was quantitated using linear calibration curves obtained at 280
      nm. This method allowed identification and quantitation of iodoamino acids from
      diverse sources in the range 2-500 ng, avoiding the need to radiolabel samples.
      The technique was tested with in vitro iodinated and non-iodinated human
      thyroglobulin and the recoveries ranged from 84 to 91%.

PMID- 9029325
TI  - High-performance liquid chromatographic determination of N-alpha-acetyl-L
      carnosine in equine plasma.
AB  - N-alpha-Acetyl-L-carnosine (NAcCAR) in perchloric acid extracts of equine plasma
      was assayed by high-performance liquid chromatography on a 3 microns Hypersil ODS
      (150 x 4.6 mm I.D.) column eluted with 5 mM phosphoric acid-1 mM triethylamine,
      pH 2.58. NAcCAR was isolated by solid-phase extraction on Isolute PRS
      (propylsulphonyl) columns. The HPLC mean retention time for NAcCAR was 5.9 +/-
      0.2 min. The recovery from plasma by solid-phase extraction was 93.9-99.7% and
      lower limit of detection in plasma was 0.18 microM. The normal NAcCAR
      concentration in equine plasma was 2.4 +/- 0.3 microM. The method was applied to
      the determination of plasma concentrations following oral and intravenous NAcCAR
      administration.

PMID- 9029326
TI  - Simultaneous determination of carbamazepine and its metabolites in plasma from
      carbon tetrachloride-intoxicated rats using a new reversed-phase chromatographic
      column of 2-microns porous microspherical silica gel.
AB  - A high-performance liquid chromatographic method has been developed for the
      simultaneous analysis of carbamazepine (CBZ) and its two metabolites,
      carbamazepine-10,11-epoxide (CBZ-E) and carbamazepine-10,11-dihydroxide (CBZ
      diOH), using a recently developed reversed-phase column with 2-microns particles
      and a 2-microliters microflow cell equipped with a UV detector. The separation
      was achieved using two different C18 reversed-phase columns (column 1: 100 x 4.6
      mm I.D., particle size 2 microns, TSK gel Super-ODS; column 2: 100 x 4.6 mm I.D.,
      particle size 5 microns, Hypersil ODS-C18) for comparison. The mobile phase was
      composed of methanol-water (30:70, v/v), and the flow-rate was 0.4 ml/min for
      both columns. The absorbance of the eluent was monitored at 210 nm. Retention
      times with column 1 were shorter than with column 2. When the three compounds
      were determined, the sensitivity and limit of quantification were about ten times
      better with column 1 than with column 2. The relative recovery and linearity with
      column 1 were approximately the same as those with column 2. These results show
      that the new ODS column packing with a particle size of 2 microns gives a higher
      sensitivity and shorter analysis time than the conventional ODS column packing.

PMID- 9029327
TI  - Everyday heroes in ethics: Part I.

PMID- 9029328
TI  - Where are the heroes of bioethics?

PMID- 9029329
TI  - Heroes, martyrs, and other choices.

PMID- 9029330
TI  - Perhaps we all be heroes.

PMID- 9029331
TI  - Reflections on my father's experience with doctors during the Shoah (1939-1945).
      Interview by Harold J. Bursztajn.

PMID- 9029332
TI  - Feminist approaches to bioethics.

PMID- 9029333
TI  - She said/he said: ethics consultation and the gendered discourse.

PMID- 9029335
TI  - A model policy addressing mistreatment of medical students.

PMID- 9029334
TI  - A feminist standpoint for genetics.

PMID- 9029336
TI  - Family dynamics and children in medical research.

PMID- 9029337
TI  - Audience and authority: the story in front of the story.

PMID- 9029338
TI  - Fantasies, coping behavior, and psychopathology.
AB  - This study assessed whether consistent relationships exist between the content of
      self-reported coping behaviors, sustaining fantasies, and ordinary daydreams. A
      second goal was the identification of coping behaviors associated with
      psychopathology and an exploration of connections between coping behaviors,
      fantasies, and daydreams correlated with pathology. College students (N = 119)
      completed the Tanck and Robbins Coping Behaviors Scale, the Sustaining Fantasy
      Questionnaire, and 12 Imaginal Processes Inventory scales. Pearson correlations
      indicated strong support for similar content between coping behaviors and the two
      types of fantasy. Previously reported relationships between coping behaviors and
      psychopathology were replicated. Significant intercorrelations were found between
      sustaining fantasies, daydreams, and coping behaviors that, separately, were
      found to be significantly associated with psychopathology.

PMID- 9029339
TI  - Construct validity of the Rorschach Oral Dependency (ROD) Scale: relationship of
      ROD scores to WAIS-R scores in a psychiatric inpatient sample.
AB  - Three-hundred and two psychiatric inpatients (166 women and 136 men) completed
      Masling, Rabie, and Blondheim's Rorschach Oral Dependency (ROD) Scale and the
      Weschler Adult Intelligence Scale Revised (WAIS-R). As predicted, ROD scale
      scores were unrelated to WAIS-R scores in subjects of either sex. These findings
      support the discriminant validity of the ROD scale as a measure of interpersonal
      dependency, and suggest that deficits in intellectual ability do not underlie the
      dependency-related behaviors (e.g., suggestibility, conformity, interpersonal
      yielding) that are associated with high scores on the ROD scale. Implications of
      these findings for research on the dependency-academic performance relationship
      are discussed, and suggestions for future studies assessing the convergent and
      discriminant validity of the ROD scale are offered.

PMID- 9029340
TI  - Codependency as a mediator between stressful events and eating disorders.
AB  - This study examined the role of codependency in the relationship between
      stressful events and the development of eating disorders. Ninety-five
      undergraduate women completed the Codependency Assessment, the Eating Disorder
      Inventory-2, the Differentiation of Self Scale, and an open-ended questionnaire
      asking about stressful experiences, including relationships with alcoholic family
      members. Results supported the hypothesis that women who reported experience with
      an alcoholic significant other or a chronic stressful situation exhibited higher
      levels of eating disordered behavior. However, a family history of parental
      alcohol abuse alone did not result in differences in eating disorder symptoms.
      Further, women who exhibited more characteristics of codependency (e.g.,
      caretaking, needs for control) also evidenced more eating disorder symptoms. The
      findings suggest a developmental sequence, whereby codependency mediates the
      relationship between excessive stress and the development of an eating disorder.

PMID- 9029341
TI  - Performance variability as a new theoretical mechanism regarding eating disorders
      and cognitive processing.
AB  - Bulimic (n = 23) and control subjects (n = 28) were compared on four
      neuropsychological tests and several clinical variables. Between-group
      differences were observed on neuropsychological measures that reflected marked
      impulsivity and problem-solving deficits in the bulimics. Additional between
      group comparisons, based on the variability of performance on the
      neuropsychological tests, revealed that bulimics were more variable than controls
      on approximately 50% of the tests given Performance variability on the remaining
      two tests was equal across the bulimic and control groups. This represents the
      first known application of this performance variability analysis in subjects with
      bulimia nervosa. It is proposed that there may be considerable variability in
      performance among bulimics and that by examining performance from this "sub
      group" perspective may lead to a more analytic understanding of this eating
      disorder.

PMID- 9029342
TI  - A two-factor model of dietary restraint.
AB  - The present study was designed to examine the factorial nature of the Three
      Factor Eating Questionnaire-Restraint Scale (TFEQ-R) and to compare the
      relationship of both the Restraint Scale (RS) and TFEQ-R to current dieting,
      history of dieting, disinhibition, self-esteem and restrained drinking in 144
      females. A principal component analysis identified three interpretable factors:
      Emotional/Cognitive Concern for Dieting, Calorie Knowledge, Behavioral Dieting
      Control. Only Emotional/Cognitive Concern for Dieting equated with RS as both
      measures correlated with self-esteem and restrained drinking. Results are
      discussed in light of other proposed models of dietary restraint and in relation
      to two recent factors which have been identified in the drinking literature,
      Cognitive Emotional Control and Cognitive Behavioral Control.

PMID- 9029343
TI  - Childhood leukemia and body image: interview reveals impairment not found with a
      questionnaire.
AB  - Twenty-eight adolescent leukemia survivors and 34 healthy controls were examined
      by means of a self-report questionnaire and a semi-structured face-to-face
      interview to appraise the quality of their body image. To protect against
      observer bias a blind-rater was used. The self-report inventory suggested that
      survivors have a perfectly normal body image, whereas in the interview 36% of the
      survivors were rated as having an impaired and 36% a diffuse, body image. The
      survivors' characteristic attitude towards their physical appearance--to evade
      the difficult issue--because evident when there were no ready answers from which
      to choose. Thus, in evaluating the impact of cancer on body image the choice of
      method of inquiry is vital.

PMID- 9029344
TI  - Cultural pathways toward Antonovsky's sense of coherence.
AB  - This study empirically validated Antonovsky's suggestion that differing cultural
      pathways exist in the development of a Sense of Coherence Differences were found
      in the ways in which essentially identical levels of a Sense of Coherence were
      developed in Native Americans and Anglo-Americans. Native Americans' families
      appear to emphasize moral and religious values while Anglo-American families
      appear to emphasize achievement and independence.

PMID- 9029345
TI  - Indicators of feminine gender identity in latency-aged boys in the Draw a Person
      and the Rorschach tests.
AB  - Seven diagnostic indicators were examined for their potential to identify latency
      aged boys who had feminine gender identity. Nineteen emotionally disturbed boys
      (average age 10.2) with feminine gender identity were compared on these
      indicators with 21 control boys. The indicators which were found to be valid were
      drawing the female figure with a greater value than the male figure in the DAP;
      difficulty in identification with the male figure in stories to the DAP; a low
      relative rate of male human responses and/or a high relative rate of female human
      responses in the Rorschach; and initial butterfly response to card V in the
      Rorschach. Using these indicators in combination reduced the false positive and
      negative rates associated with each individual indicator.

PMID- 9029346
TI  - Alexithymia and dissociative tendencies.
AB  - This study is one of a series exploring the potential of affective variables as
      predictors of dissociative tendencies. Some clinicians have observed that
      traumatized children who develop a dissociative coping style also tend to fail to
      discriminate emotions by verbal means. The study therefore investigated a
      relationship between dissociation and alexithymia. Undergraduate psychology
      students were individually tested for dissociative tendencies, alexithymic
      characteristics, and ability to generate the names of emotions. Dissociation was
      found to be predicted by some aspects of alexithymia but not by affective
      fluency. The data are interpreted in terms of the concept of asymmetry of
      dissociative processes.

PMID- 9029347
TI  - Perception of body shapes by anorexics and mature and teenage females.
AB  - Three groups of females-Anorexic (mean age 28). Teenage (mean age 16), and Mature
      adults (mean age 27)-were shown four male and four female body drawings ranging
      from very thin to very fat and asked to rate them on four categories (attractive,
      healthy, confident, and popular) using a 10-point bipolar scale. A predicted and
      consistent pattern occurred, namely that the anorexics rated fatter women less
      attractive, less healthy, less confident and less popular than teenagers and
      mature females, while at the same time rating male body shapes more attractive
      than did the two other female groups. Both anorexic and teenage groups rated the
      thinner women as more attractive, healthy, confident, and popular than the mature
      females. Both mature and teenage females rated the fat female body shape more
      positively than did the anorexics. The implications of these findings are
      discussed.

PMID- 9029348
TI  - Coping and problem solving of self-mutilators.
AB  - People who self-mutilate have been hypothesized to have deficient skills in
      coping and problem-solving that leave them vulnerable to the adoption of self
      mutilation as a coping strategy. This hypothesis was tested using male
      incarcerated self-mutilators with comparisons being made with non-multilating,
      prisoner, and non-prisoner control groups. Examination of the inherent resources
      which enable an individual to effectively cope with stress demonstrated a
      depressed score for self-mutilators on the scale measuring self-worth and
      optimism about life. Assessment of the strategies used to cope with real problems
      demonstrated that self-mutilators engage in more problem avoidance behaviors.
      Self-mutilators also recorded less perceived control over problem-solving
      options. The results are discussed in terms of the effectiveness of self
      mutilation as a coping strategy and the need to adopt a multidimensional approach
      to the investigation of coping.

PMID- 9029349
TI  - Psychological functioning of adolescent transsexuals: personality and
      psychopathology.
AB  - Adolescent transsexuals were compared with adolescent psychiatric outpatients and
      first-year university students to determine the extent to which other
      psychopathology is a necessary condition for the development of transsexualism.
      Three areas of psychological functioning associated with fundamental
      psychological disturbances--perceptual inaccuracy, disorders of thought and
      negative self-image--were assessed by means of the Rorschach Comprehensive
      System. The group of adolescent transsexuals was found to be intermediate between
      adolescent psychiatric patients and nonpatients for extent of perceptual
      inaccuracy. They did not differ significantly from nonpatients with regard to
      thinking disturbances and negative self-image. The psychiatric patients included
      significantly more individuals characterized by negative self-image than the
      other groups. The results support the idea that major psychopathology is not
      required for the development of transsexualism.

PMID- 9029350
TI  - Immunomodulatory activity of beta-casein permeate medium fermented by lactic acid
      bacteria.
AB  - During fermentation, lactic acid bacteria may be able to release components that
      possess immunomodulatory activity. This activity was investigated in several
      culture supernatants arising from lactic acid bacteria cultured in a medium
      composed primarily of UF permeate of bovine milk; beta-CN was added as the sole
      protein source. Only a Lactobacillus helveticus supernatant allowed the
      modulation (both suppression and enhancement) of lymphocyte proliferation in
      vitro on human peripheral blood lymphocytes, but L. helveticus did not modulate
      the cytotoxic activity of natural killer cells or of lymphokine-activated killer
      cells. The addition of different quantities of culture supernatant to cultures of
      human mononuclear cells, stimulated by the mitogen concanavalin A, significantly
      increased the production of interferon-gamma and decreased the production of
      interleukin-2 and the expression of the alpha-chain of the interleukin-2 receptor
      (p55), all of which appear to be correlated with the decrease in lymphocyte
      proliferation. Our results suggest that the culture supernatant activity might be
      related to interaction with monocyte-macrophage and T helper cells, especially
      Th1-like cells.

PMID- 9029352
TI  - Viscosity and density of lactulose solutions.
AB  - The density and viscosity of solutions of lactulose and solutions of lactulose
      and boric acid were determined using calibrated viscometers and a nominal 10-ml
      pycnometer, respectively. These data were necessary for the development of the
      recovery section of a continuous pilot plant process to produce lactulose, a
      valuable pharmaceutical, from lactose.

PMID- 9029351
TI  - Hypocholesterolemic action of Lactobacillus acidophilus ATCC 43121 and calcium in
      swine with hypercholesterolemia induced by diet.
AB  - Thirty-three Yorkshire barrows (92 kg), fed a high cholesterol diet for 14 d had
      mean concentrations of serum cholesterol of 294.6 +/- 7.8 mg/dl. Starting on d 15
      and for an additional 15 d, crystalline cholesterol was removed from the diet and
      pigs were assigned to one of four treatments: including two levels of calcium
      (0.7% and 1.4%) with and without added viable Lactobacillus acidophilus ATCC
      43121 (2.5 x 10(11) cells per feeding). Serum cholesterol levels decreased, as
      expected, for all groups. However, the declines were initiated sooner for the
      groups receiving L. acidophilus. and those receiving the high level of calcium
      than for the respective control groups. When averaged over days, pigs fed L.
      acidophilus had 11.8% lower total cholesterol than pigs fed a diet without L.
      acidophilus. Similarly, pigs fed 1.4% calcium had a significantly lower total
      cholesterol than pigs fed 0.7% calcium. The effects were greater on low density
      lipoprotein cholesterol than on high density lipoprotein cholesterol. In
      addition, during the overall 15-d experimental period, serum bile acids were
      reduced 23.9% by dietary L. acidophilus and by 21.4% by 1.4% dietary calcium
      compared with those of their controls. Total bile acid concentration was
      positively correlated with total cholesterol concentration for pigs fed L.
      acidophilus or 1.4% calcium. These data suggest that both L. acidophilus and
      calcium can enhance the reduction of serum cholesterol in pigs that had been fed
      a high cholesterol diet, probably through alteration in the enterohepatic
      circulation of bile acids.

PMID- 9029353
TI  - Modulation of postthaw motility, survival, calcium uptake, and fertility of
      bovine sperm by female genital products.
AB  - Because the different portions of the female genital tract act in many ways on
      sperm metabolism, the current study was undertaken to modulate the survival and
      fertilizing ability of bovine semen by incorporation of products from the oviduct
      or the follicle in extenders before freezing. Motility rates at 6 h in vitro
      showed a net positive effect when biological factors from total retentate or from
      a fraction of bovine follicular fluid (total retentate = 43%; fraction 2 = 54%),
      oviductal cell culture (total retentate = 43%; fraction 2 = 58%), or granulosa
      cell culture (total retentate = 43%; fraction 3 = 53%) were added to the
      extenders compared with the addition of BSA (31%). Fraction 3 of granulosa cell
      culture retentate also had a significant stimulatory effect on the number of
      sperm that penetrated mucus of cows in estrous compared with BSA (n = 205 vs. n =
      159). The intracellular sperm Ca2+ concentrations were very different across
      treatments after thawing. Sperm from straws with BSA had the highest
      concentration. At 4 h, intracellular Ca2+ concentration increased for all
      treatments, except that for sperm treated with BSA and Ca alone, internal Ca2+
      declined. Heparin plus Ca stimulated a greater internalization of Ca2+ than did
      Ca alone for retentate from bovine follicular fluid, oviductal cell culture, and
      BSA treatments: glucose consistently and significantly reduced internalization.
      In vitro fertilization rates were similar, and no significant differences were
      observed across treatments.

PMID- 9029354
TI  - Modulation of postthaw motility, survival, calcium uptake, and fertility of
      bovine sperm by magnesium and manganese.
AB  - Because Mg2+ and Mn2+ are potent stimulators of motility through the stimulation
      of adenylate cyclase activity, the current study was undertaken to modulate the
      fertilizing ability of bovine semen by incorporation of various concentrations of
      those two salts in extenders before freezing. Motility analysis at 6 h in vitro
      showed a positive effect of MgCl2 in a dose-dependent manner from 0.5 to 5 mM (31
      to 50%). Manganese at the concentration of 0.1 mM also supported good sperm
      motility (53%) compared with that of the control (28%). Although survival was
      increased, no detrimental effects were seen on the number of sperm that
      penetrated mucus of cows in estrus. The intracellular Ca2+ concentration of sperm
      was very different across treatments after thawing; spermatozoa that were
      extended with 2 mM MgCl2 and 0.5 mM MnCl2 possessed the highest concentrations at
      thawing. Four hours later, in the presence of Ca, spermatozoa that were extended
      in 0.1 mM MnCl2 showed the highest uptake. In the presence of Ca and heparin,
      spermatozoa that were extended in different amounts of Mg showed Ca2+
      concentrations that increased in a dose-dependent manner. This effect was negated
      by glucose. Functional fertilizing capacity was also evaluated by in vitro
      fertilization, and the different treatments did not show any detrimental effects.
      In summary, 5 mM MgCl2 and 0.1 mM MnCl2 both have beneficial effects for the
      maintenance of sperm motility without detrimental effects on mucus penetration
      and fertilizing ability. Furthermore, these treatments do not prevent subsequent
      Ca2+ uptake in response to heparin. These in vitro studies are potentially a good
      sorting system to predict the benefits of extender modifications.

PMID- 9029355
TI  - Effect of bovine somatotropin administered to periparturient dairy cows on the
      incidence of metabolic disease.
AB  - Thirty-eight dry, pregnant Jersey cows were assigned to diet and bST treatment in
      a 2 x 2 factorial design. During the dry period, half of the cows were fed a
      normal TMR (0.4% Ca; 0.3 to 0.4% P), and half of the cows were fed a high Ca TMR
      (1.5 to 1.6% Ca; 0.4 to 0.7% P). The high Ca diets were designed to induce milk
      fever and were relatively cationic (194 to 293 meq/kg) compared with the normal
      diets (-131 to 30 meq/kg). A standard dairy diet was fed to all cows postcalving.
      Cows received subcutaneous injections of either an oil-based excipient or 500 mg
      of bST in an oil-based excipient every 14 d from 28 d before expected calving
      until approximately 14 d postcalving. Peripartal bST treatment decreased the
      incidence of clinical mastitis, did not affect incidence of milk fever, and
      increased the duration, but not the incidence, of ketosis in mature Jersey cows.
      Blood data confirmed the clinical responses and indicated that treated cows
      mobilized more bone Ca than did controls, as was evidenced by increased
      hydroxyproline concentrations. Treatment with bST did not affect blood
      concentrations of 1,25-dihydroxyvitamin D, Ca, or Mg. High Ca diets increased the
      incidence of milk fever and downer cow syndrome compared with normal diets. The
      effect of bST on mastitis and milk production must be considered as preliminary
      given the small size of the study. Although bST treatment increased Ca
      mobilization, the effect was insufficient to prevent milk fever in this model.

PMID- 9029356
TI  - Acidosis effects on insulin response during glucose tolerance tests in Jersey
      cows.
AB  - The effect of metabolic alkalosis and acidosis on insulin response to glucose
      tolerance tests was determined for cows fed a high cation diet to induce a state
      of metabolic acidosis. The anion diet to induce a state of metabolic acidosis.
      The glucose tolerance test (500 mg of glucose/kg of BW infused i.v. over 10 min)
      caused a rapid increase in plasma glucose and insulin concentrations. Plasma
      glucose concentrations were highest, and plasma insulin concentrations were
      lowest, during metabolic acidosis. These results suggest that insulin secretion
      is impaired during metabolic acidosis, which may reduce tissue uptake of glucose.
      Correction of metabolic acidosis by oral administration of sodium bicarbonate
      prior to glucose tolerance testing increased blood pH and bicarbonate
      concentrations and partially restored insulin response to the glucose tolerance
      test. Interestingly, sodium bicarbonate also caused an elevation in plasma
      cortisol concentrations. We concluded that glucose utilization is altered in cows
      with metabolic acidosis. The correction of acidosis associated with diseases such
      as diarrhea and ketosis may improve the therapeutic benefit of glucose infusions
      used to treat these diseases.

PMID- 9029357
TI  - Bovine mastitis caused by Listeria monocytogenes: kinetics of antibody responses
      in serum and milk after experimental infection.
AB  - The kinetics of antibodies in serum and milk directed against proteins from
      Listeria monocytogenes were studied using 4 lactating cows after infection was
      experimentally induced in the udder with four strains of serotypes 4b or 1/2a.
      Antibodies (IgG and IgA) in samples of composite quarter milk and serum of the
      cow were measured by indirect ELISA. Microtiter plates were coated with proteins
      obtained from the culture supernatant of L. monocytogenes 4b. After challenge, an
      IgG response in serum and milk to listerial infections in the udder occurred for
      all cows, although the response varied among cows. In sera, the IgG titers
      reached a peak at 9 to 13 wk after challenge and remained elevated until 21 to 33
      wk after challenge. In milk, the IgG titer increased significantly 3 wk after the
      challenge for all cows. A weak and nonpersistent increase in IgA antibodies also
      occurred. These results indicate that IMI by L. monocytogenes induced an increase
      of antibodies in milk, which could be detected with an ELISA test using our
      antigenic preparation. Therefore, this antigenic preparation could be used for
      the evaluation of a new method of diagnosis for bovine mastitis caused by L.
      monocytogenes.

PMID- 9029358
TI  - Effect of glucose fermentation on fiber digestion by ruminal microorganisms in
      vitro.
AB  - Two in vitro digestion trials were performed to determine whether the negative
      effect on fiber digestion when pH was maintained at > 6.2 was attributable to
      glucose alone or to end products of glucose fermentation. In some treatments,
      glucose was depleted by a previous 6-h incubation; the supernatant from this
      incubation was used as the buffer source for treatments using the fermented
      glucose medium. In trial 1, mixed cultures were grown on cellulose, soybean
      hulls, and corn bran in fresh media with 0 (control) or 25 mM glucose, in media
      previously fermented for 6 h with 0 (control) or 25 mM glucose, or in fermented
      control medium plus 25 mM lactic acid. The rate of NDF digestion was decreased
      with fermented glucose medium but not with fresh glucose medium or lactic acid
      medium. Concentrations of lactate, propionate, and butyrate did not appear to
      affect NDF digestion directly. In trial 2, six treatment media were used: control
      and glucose media that were either fresh or previously fermented for 6 h and
      fermented control and glucose media treated with a protease. Rate of NDF
      digestion was slower in cultures with fermented glucose medium that was treated
      with protease than in fermented control medium without protease. When treated
      with protease, rate of NDF digestion was not different between the fermented
      control medium and the fermented glucose medium. Thus, the negative effect on
      fiber digestion appeared to be attributable partially to a proteinaceous
      inhibitor that was produced in culture media containing a rapidly fermented
      sugar.

PMID- 9029359
TI  - Kinetics of cell-wall digestion of orchardgrass and alfalfa silages treated with
      cellulase and formic acid.
AB  - The objectives of this study were to determine the effects of cellulase (from
      Trichoderma longibrachiatum) combined with formic acid, applied before ensiling,
      on the subsequent concentration and composition of the cell wall and on the
      extent and rate of in situ cell-wall digestion of orchardgrass (Dactylis
      glomerata L.) and alfalfa (Medicago sativa L.). Treated and control forages of
      both plant species were ensiled for at least 60 d before being ruminally digested
      by two fistulated cows. Analyses of NDF, ADF, and acid detergent lignin were
      conducted sequentially on original and digested samples. Data were fitted with a
      first-order, nonlinear model to estimate extents and rates of digestion of
      potentially digestible NDF, cellulose, and hemicellulose. The concentration of
      indigestible residue and the discrete lag time before digestion were also
      determined for the cell-wall components. After ensiling, the mean NDF
      concentration of treated silages was 19% lower than that of control silages; the
      effect was greater for orchardgrass than for alfalfa. The extent of digestion of
      NDF, cellulose, and hemicellulose, respectively, was 33, 37, and 27% lower for
      treated silages than for control silages. Treatment effects on the extent of
      digestion varied between plant species. Cellulose from treated orchardgrass was
      digested 19% more slowly than cellulose from the control silage. Indigestible
      residue concentrations of NDF, cellulose, and hemicellulose, respectively, were
      7, 8, and 7% lower in treated silages than in control silages. Thus, extensive
      cell-wall degradation by cellulase during ensiling resulted in less digestible
      cell-wall material for ruminal digestion but greater total cell-wall degradation,
      including that during ensiling and ruminal incubation, especially during early
      digestion in the rumen.

PMID- 9029360
TI  - Effect of intravenous amino acid infusion on leucine oxidation across the mammary
      gland of the lactating goat.
AB  - Changes in the kinetics of leucine in the mammary gland were examined in four
      lactating goats (25, 38, 45, and 135 DIM) that were given an i.v. infusion of a
      mixture of 18 AA, not including leucine, to alter the availability of leucine to
      the gland relative to other AA. Arteriovenous monitoring of [1-13C]leucine
      kinetics across one-half of the mammary gland was conducted on the last day (d 6
      or 7) of the saline (control) and the AA infusion periods. Although blood flow to
      the mammary gland and the arterial concentration of most AA other than leucine
      were increased by the AA infusion, milk and protein yields did not change. For
      goats in early lactation (n = 3), arterial leucine concentrations fell
      considerably during AA infusion; however, the arteriovenous difference of leucine
      was maintained, resulting in uncommonly low leucine concentrations in venous
      plasma (8 microM). Whole body leucine flux (protein synthesis plus oxidation) was
      unaffected by AA infusion, but, because whole body leucine oxidation was reduced,
      whole body utilization of leucine for protein synthesis increased. The AA
      infusion reduced mammary oxidation of leucine to approximately one-third of
      control values. These results suggest that leucine oxidation can be reduced
      considerably without affecting milk protein output; thus, leucine oxidation may
      not be an irrevocable consequence of mammary metabolism. If catabolism of other
      AA either by the gland or in the whole body can be reduced, then the efficiency
      of milk yield can be improved.

PMID- 9029361
TI  - Effects of dietary crude protein, breed, parity, and health status on the
      fertility of dairy cows.
AB  - A study was conducted to determine the impact of dietary CP (13% vs. 20%), parity
      (first vs. second lactation or later), and breed (Holstein vs. Jersey) on the
      reproductive efficiency of dairy cows. Sixty-four cows were blocked by parity and
      breed and assigned to one of two treatments. Cows were removed from treatments on
      d 100 or 120 depending on pregnancy status. Cows were categorized by health
      status based on the occurrence of postparturient disorders. Plasma urea N
      concentrations were influenced by diet (8.6 vs. 21 mg/dl, 13 and 20% CP,
      respectively), parity, and breed. Reproductive indices were not influenced by
      diet except that days to first estimated ovulation increased for cows fed the 20%
      CP diet when health status was added to the model. Days to first observed estrus,
      first AI service, and cumulative pregnancy rate were affected by health status.
      Regression analysis for survival showed an interaction of diet and health status
      for days open. High CP diets tended to increase days open when cows had major
      health problems; otherwise, a high CP diet decreased days open. The
      implementation of a strict reproductive management program allowed high
      reproductive efficiency goals to be achieved regardless of plasma urea N
      concentrations.

PMID- 9029362
TI  - Effects of supplemental chromium on production of cytokines by mitogen-stimulated
      bovine peripheral blood mononuclear cells.
AB  - This study determined whether supplementing the diets of dairy cows during the
      peripartum period with organic trivalent Cr influenced the capacity of their
      peripheral blood mononuclear cells to produce activation cytokines in response to
      stimulation with mitogens in vitro. Nine cows were fed 0.5 ppm of Cr/d per cow
      from 6 wk prepartum to 16 wk postpartum; 10 other periparturient cows served as
      unsupplemented controls. Mononuclear leukocytes, enriched from peripheral blood
      during wk 0, 2, 4, and 6 of lactation, were cultured with or without the T
      lymphocyte mitogen, concanavalin A. Culture supernatants, harvested at 24, 48, or
      72 h, were assayed for interleukin-2, interferon-gamma, and tumor necrosis factor
      alpha. The cytokines were barely detectable in the supernatants from the
      unstimulated cultures, but supernatants from mitogen-stimulated cultures
      contained higher concentrations of each cytokine. For cows fed Cr, concentrations
      of all three cytokines in the culture supernatants of the mitogen-stimulated
      mononuclear cells decreased significantly relative to values for unsupplemented
      cows, particularly around peak lactation for the 24- and 48-h cultures. Theses
      results extended our previous observations and supported the hypothesis that
      organic Cr is immunomodulatory in high producing cows.

PMID- 9029363
TI  - Influence of niacin supplementation on in vivo digestibility and ruminal
      digestion in dairy cows.
AB  - The effect of niacin supplementation on digestion was investigated using four
      cows in a crossover design. After peak lactation, cows received a diet of corn
      silage (55%) and concentrates (45%), including a formaldehyde-treated mixture of
      soybean meal, rapeseed meal, and urea. This diet was either supplemented with
      niacin (6 g/d) or not supplemented. Total tract apparent digestibility of OM and
      fiber and ruminal digestibility of OM were not modified by treatment. Niacin
      supplementation enhanced the theoretical degradability of ruminal DM in situ
      (44.7% vs. 40.6%) and concentration of protozoa in ruminal fluid (459 vs. 311 x
      10(3)/ml), especially Ophryoscolecidae. The percentage of butyrate in the VFA
      mixture of ruminal fluid was increased by niacin supply, but acetate and
      propionate percentages and total VFA concentration did not vary. Ruminal digesta,
      ruminal pools, and ruminal kinetics were not affected by treatment. Duodenal flow
      of nonmicrobial N tended to increase with niacin supplementation. Duodenal flow
      of microbial N did not vary, as measured using a microbial sample, for fluid
      associated bacteria or for a mixture of fluid-associated and particle-associated
      bacteria. These results are discussed in relation to the characteristics of the
      diet.

PMID- 9029364
TI  - Influence of weaning method on growth, intake, and selected blood metabolites in
      Jersey calves.
AB  - Forty-three Jersey calves were assigned randomly at birth to treatments that
      evaluated the method of weaning on growth, intake, and concentrations of blood
      metabolites that were indicative of ruminal development. The three experimental
      treatments were 1) milk replacer fed at 10% of BW until abrupt weaning at 35 d of
      age, 2) milk replacer fed at 10% of BW until 28 d and then at 5% of BW until
      weaning at 35 d of age, or 3) milk replacer fed at 10% of BW until intake of calf
      starter reached 454 g/d for 2 consecutive d, at which time calves were weaned.
      Commercial milk replacer was reconstituted to 12.5% DM and fed twice daily.
      Commercial calf starter was offered from 3 d of age. When milk replacer was fed
      at 5% of BW from 29 to 35 d, BW gain was reduced compared with that of calves on
      the other treatments; however, BW at 56 d was unaffected by treatment.
      Concentrations of NEFA and blood urea N were higher from 29 to 56 d than when
      calves were fed milk replacer at 5% of BW from 29 to 35 d. Blood BHBA increased
      as starter DMI increased and was unaffected by treatment. Intake of milk replacer
      and feed cost were greater for calves that were weaned when calf starter intake
      reached 454 g/d for 2 consecutive d. For calves that were weaned according to
      intake, mean age at weaning was 40 d.

PMID- 9029365
TI  - Genetic parameters of longevity traits of an upgrading population of dairy
      cattle.
AB  - Longevity reflects the ability of a cow to avoid being culled for low production,
      low fertility, or illness. Longevity could be used in breeding programs if
      genetic parameters were known. Various measures are used for longevity. In this
      study, lifetime measures including number of lactations, total milk production,
      number of days in lactation, herd life, and length of productive life were
      analyzed. Also analyzed were stayability measures (dead or alive) to 36, 48, 60,
      or 72 mo of age and to 12, 24, 36, or 48 mo of productive life. Measures of
      longevity were also analyzed after correction for milk production during first
      lactation (functional longevity traits). Data on 1,72,988 cows were used to
      calculate means for longevity traits per year of birth. All cows were known to
      have been culled. Longevity decreased from 1978 through 1984 and increased in
      1985. Possible causes for the decrease of longevity were implementation of the
      quota system and introduction of Holstein genes. heritabilities of longevity
      traits were estimated for cows born in 1985 (38,957 records), 1982 (166,324
      records), and 1978 (94,935 records) after data were edited to require at least 25
      daughters per sire and 10 cows per herd. Phenotypic and genetic correlations were
      estimated for the 1985 data. Heritability estimates differed between years of
      birth, and estimates of functional traits were lower than those of uncorrected
      longevity traits. Genetic correlations between uncorrected longevity traits were
      high (0.733 to 1.000); phenotypic correlations were lower (0.131 to 0.980).
      Genetic correlations between uncorrected and functional longevity traits were
      high (0.577 to 0.975).

PMID- 9029366
TI  - Genetic parameters and trends for milk production of blond-faced Latxa sheep
      using Bayesian analysis.
AB  - The genetic progress attained with the breeding scheme of the blond-faced Latxa
      dairy sheep in the Spanish Basque Country was assessed by a Bayesian approach
      based on the marginal posterior distributions of parameters achieved via Gibbs
      sampling. The data file included 49,056 milk yield records of 22,363 ewes. Normal
      distributions were assumed for EBV and fixed effects, and scaled inverted chi
      square distributions were assumed for variance components or additive, permanent
      environment, and residual effects. Under vague priors for variance components,
      the posterior means (SD) for heritability and permanent environment coefficient
      for milk yield at 120 d were 0.22(0.01) and 0.20(0.01). An important effect on
      the milk yield (41.6% of the mean) was evident for a genetic group of imported
      rams. Selection was effective for sheep that were bred by AI and that had known
      parents. The robustness of results for effect of genetic group and genetic trends
      was validated using a mildly informative prior constructed from variance
      components estimated with the related black-faced Latxa breed.

PMID- 9029367
TI  - Milk yield and composition of dairy cows fed concentrate based on high moisture
      wheat or high moisture corn.
AB  - Thirty-six Ayrshire cows were assigned to 18 pairs and were blocked within parity
      (5 pairs of primiparous heifers and 13 pairs of multiparous cows); pairs had
      similar calving dates. The study, which was conducted over 3 yr, was designed to
      determine the effects of high moisture grain on milk yield and composition and to
      determine in vitro DM digestibility and ruminal degradabilities of DM, N, and
      starch of high moisture grains. Treatment diets consisted of isonitrogenous and
      isoenergetic concentrates that were based on high moisture wheat or high moisture
      corn. Both groups were fed a mixture of grass silage, grass hay, protein
      supplement, and a vitamin and mineral mix for ad libitum intake. Treatment diets
      were fed from wk 4 to 29 and from wk 4 to 37 of lactation for cows in first and
      second lactations, respectively. There was no interaction between treatment diet
      and year of lactation. Cows fed high moisture wheat had higher 4% FCM than did
      cows fed high moisture corn. Milk composition was similar for the two treatment
      diets. Ruminal degradabilities of DM and starch were higher for high moisture
      wheat than for high moisture corn. In vitro DM digestibility was higher for high
      moisture wheat (90.5%) than for high moisture corn (71.6%). This greater
      digestibility contributed to the higher milk yield of dairy cows fed high
      moisture wheat.

PMID- 9029368
TI  - Are ruminal bacteria armed with bacteriocins?
AB  - The production of toxic compounds or antibiotics is a common component of
      intermicrobial competitive interactions, and many of these toxins have been
      adopted and adapted for the control of microbial populations. One class of these
      toxins, the bacteriocins, is a heterogeneous group of proteinaceous antibiotics
      that often display a high degree of target specificity, although many have a very
      wide spectrum of activity. To date, only limited information is available
      concerning the occurrence of bacteriocins among ruminal isolates or the
      sensitivity of ruminal microorganisms to exogenous bacteriocins. A survey of 50
      strains of Butyrivibrio spp. isolated from a variety of sources (sheep, deer, and
      cattle) for bacteriocin production indicated a high incidence of bacteriocin-like
      activity (50%). Many of these inhibitory compounds appear to have a broad
      spectrum of activity, which suggests that bacteriocins may have a significant
      impact on both the competitive fitness of individual microbial strains within the
      rumen and on the overall structure of the microbial population within the rumen.
      Selected bacteriocins from lactic acid bacteria also were shown to have activity
      against Butyrivibrio spp. and may have application in ruminant systems.
      Bacteriocins may provide an alternative group of antibiotics for the manipulation
      of ruminal microbial populations. Bacteriocins have significant advantages over
      other antibiotics in target specificity, susceptibility to proteolytic digestion,
      possibility of genetic transfer and manipulation, and, in the case of some
      bacteriocins derived from lactic acid bacteria, a long history of safe use.

PMID- 9029369
TI  - PAF and haematopoiesis: IX. Platelet-activating factor increases DNA synthesis in
      human bone marrow cells.
AB  - Platelet-activating factor (PAF) is present in human bone marrow leading us to
      investigate its effect on human bone marrow cell proliferation. While PAF (0.1
      microM to 1 nM) stimulates the incorporation of [3H]thymidine by freshly isolated
      adherent human bone marrow cells, PAF has no effect on non adherent cells. A non
      metabolizable PAF agonist is more potent than PAF to stimulate thymidine
      incorporation in adherent cells. The precise role of PAF in human haematopoiesis
      in vivo remains to be clarified.

PMID- 9029370
TI  - High density lipoproteins increase cytoplasmic free calcium in bovine aortic
      endothelial cells.
AB  - This study examined the influence of human high density lipoproteins (HDL) on the
      intracellular free calcium of cultured bovine aortic endothelial cells (BAECs).
      Intracellular Ca2+ concentration ([Ca2+]i) was determined by a fluorescent
      calcium indicator, Fura-2. It was found that, in the presence of 1 mmol/L
      extracellular calcium, HDL resulted in a biphasic elevation of [Ca2+]i in BAECs,
      consisting of an initial, transient component followed by a lower, but more
      sustained component. Doses of HDL from 25 to 200 micrograms protein/ml induced
      marked concentration-dependent elevations of [Ca2+]i in BAECs. The sustained
      component was abolished by deprivation of extracellular calcium or by
      pretreatment of endothelial cells with a calcium influx blocker, NiCl2, HDL
      induced elevation of [Ca2+]i was attenuated in a concentration-dependent way by
      an inhibitor of calcium release, tetracaine. Repeated applications of HDL (100
      micrograms protein/ml) markedly blunted the initial peak component of the calcium
      transient of BAECs. These results demonstrate that both intracellular and
      extracellular calcium pools are responsible for the biphasic elevation of [Ca2+]i
      induced by HDL in cultured BAECs.

PMID- 9029371
TI  - Pharmacological characterisation of a new model of antigen-induced pulmonary late
      phase reaction in the conscious guinea pig which uses additional polymyxin B
      inhalation.
AB  - The aim of the present study was to develop a new model of allergic late-phase
      reaction in the airways of conscious guinea pigs (GPs) and to characterise it by
      pharmacological intervention. GPs were pretreated with cyclophosphamide and
      sensitized with ovalbumin (OA) in Al(OH)3. Weekly inhalations of polymyxin B were
      performed before and during sensitization and continued throughout the study
      period. Under cover of 10 mg/kg i.p. mepyramine all GPs still exhibited a
      pronounced immediate reaction (IR), peaking during the first 15 min after OA.
      Nine out of 15 GPs demonstrated, during screening, a reproducible (twice) second
      phase (late phase reaction (LPR)] of decreased airflow and tidal volume (TV),
      peaking 4-8 h after OA. In a cross over study, methylprednisolone (MP) at 30
      mg/kg p.o. (16 h and 1 h before OA) significantly inhibited the LPR at its peak
      (4-8 h) (peak decrease of TV to % of basal: control 49.4 +/- 3.7; MP 78.9 +/-
      7.5; p < 0.01: n = 7). After another booster sensitization with 2 micrograms
      OA/GP under the same conditions, the Paf-antagonist WEB 2347 at 3 mg/kg p.o. (1 h
      before OA) inhibited the LPR at its peak again (peak decrease of TV to % of
      basal: control 57.3 +/- 3.5; WEB 2347 74.8 +/- 7.6: p < 0.01; n = 6). In
      conclusion more than 50% of repeatedly ovalbumin sensitized (and polymyxin B
      treated) unanaesthetized GPs developed a reproducible pulmonary late phase
      reaction (LPR). The LPR peaked at 4-8 h after antigen-exposure. The inhibitory
      effect by a glucocorticoid and the Paf-antagonist WEB 2347 suggests the
      inflammatory nature of the LPR and the involvement of platelet-activating factor
      (Paf) in this model.

PMID- 9029373
TI  - Activation of rat brain protein kinase C by eicosapentaenoic acid-containing
      diacylglycerol.

PMID- 9029372
TI  - Protein kinase C inhibitors and PAF stimulate phosphatidylserine synthesis in
      human leucocytes.
AB  - To study the regulation and turnover of phosphatidylserine (PtdSer) in human
      leucocytes, we investigated the effect of 12-O-tetradecanoylphorbol 13-acetate
      (TPA), I-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3 or
      edelfosine), staurosporine and platelet activating factor (PAF) on [14C]serine
      incorporation into phospholipids. More than 80% of lipid radioactivity was in
      PtdSer. ET-18-OCH3 stimulated incorporation into PtdSer 5-fold, without
      increasing incorporation into other lipids. PAF stimulated PtdSer synthesis 3
      fold after 1 h, while staurosporine stimulated the synthesis 2-fold after 3 h.
      TPA inhibited PtdSer synthesis. It abolished the ET-18-OCH3 stimulation, and
      reduced the staurosporine stimulation. ET-18-OCH3 and TPA did not significantly
      alter the incorporation of [14C]arachidonic acid into PtdSer, and did not
      increase PtdSer turnover judged from chase and stability experiments. The results
      demonstrate that PKC inhibitors and PAF induce increased incorporation of
      [14C]serine into PtdSer, while TPA inhibits stimulated PtdSer synthesis. This
      suggests that modulation of PtdSer synthesis may regulate PKC activity in PMN
      cells.

PMID- 9029374
TI  - Anandamide--a new look on fatty acid ethanolamides.

PMID- 9029375
TI  - Exogenous diacylglycerols synergize with PAF with human platelets, but inhibit
      PAF-induced responses of rabbit platelets.
AB  - To investigate whether diacylglycerol (DAG) has a role in reversible platelet
      aggregation induced by low concentrations of platelet-activating factor (PAF), we
      attempted to use the DAG kinase inhibitor, R59022, to prevent rapid conversion of
      DAG to phosphatidic acid. However, we found that R59022 inhibited the binding of
      [3H]PAF to human and rabbit platelets and to rabbit platelet membranes. We then
      investigated whether exogenous, cell-penetrating DAGs (1,2-dihexanoyl-sn-glycerol
      (DHG) and 1-oleoyl-2-acetyl-sn-glycerol (OAG)) act synergistically with low
      concentrations of PAF that alone induce only reversible aggregation. Platelets
      were isolated and labeled with [14C]serotonin. DHG (25-75 microM) caused slow,
      weak aggregation and some release of [14C]serotonin with human, but not rabbit,
      platelets. OAG (25-75 microM) did not aggregate either species' platelets.
      Phosphorylation of pleckstrin by DHG was more transient in rabbit platelets than
      previously observed with human platelets. Both DHG and OAG synergistically
      potentiated PAF-induced aggregation of human platelets, but, paradoxically,
      concurrently inhibited the PAF-induced increase in intracellular Ca2+ ([Ca2+]i):
      potentiation decreased upon incubation with DAGs before PAF addition. In
      contrast, DHG strongly inhibited PAF-induced aggregation of rabbit platelets;
      inhibition decreased upon preincubation. OAG, added with PAF, slightly
      potentiated aggregation of rabbit platelets: upon preincubation, OAG
      progressively inhibited. Effects of DHG and OAG on PAF-induced increases in
      [Ca2+]i in rabbit platelets followed a similar pattern; thus, with rabbit
      platelets, inhibition of the [Ca2+]i increase may at least partially account for
      inhibition of PAF-induced aggregation by exogenous DAGs. Results with human
      platelets are consistent with stimulation of protein kinase C by DAGs, and then
      metabolism of DAGs and/or negative feedback by DAGs, but results with rabbit
      platelets indicate both an unexpected species difference and a difference between
      the effects of DHG and OAG on PAF-induced platelet aggregation.

PMID- 9029376
TI  - The fixative lipid of tiger pheromone.
AB  - Tigers communicate with one another with the help of Marking Fluid (MF) which is
      a lipid-rich fluid sprayed upwards and backwards through the urinary channel of
      both the sexes. The volatile molecules of the MF are made to last longer with the
      help of lipid 'fixatives' the total amount of which is 1-2 mg/ml. This lipid
      comprises cholesterol ester, wax ester, triglyceride, free fatty acids,
      diglyceride, monoglyceride, free sterol and phospholipid as revealed by thin
      layer chromatography. The gas liquid chromatogram of fatty acid methyl esters of
      the total lipid of the MF, when compared with the fatty acids of groin and body
      fat of tiger (analysed by other workers), reveals differences in higher
      proportions of palmitoleic and myristic acids and of highly unsaturated fatty
      acids. The palmitoleic acid content of total lipid and triglyceride is high in
      comparison to the wax esters and cholesterol esters of the MF-fat. The unique
      feature of the alcohol part of the wax esters is a series of saturated straight
      chain primary alcohols of C14 to C20 and these are accompanied by the
      corresponding monoenoic unsaturates.

PMID- 9029377
TI  - A retrospective analysis of Erb's palsy cases and their relation to birth weight
      and trauma at delivery.
AB  - Brachial plexus injury is assumed to be associated with the traumatic delivery of
      a macrosomic fetus in the vast majority of cases. This study was undertaken to
      examine the relationship of brachial plexus injury to birth weight and trauma at
      delivery, to compare our incidence to the incidence in other populations, and to
      examine how the incidence of brachial plexus injury has changed in our
      institution over the last 30 years. A retrospective analysis of 14,358 births
      from January 1, 1987, to June 30, 1991, identified 15 cases of brachial plexus
      injury (all Erb's palsy, incidence 0.10%). Maternal and neonatal charts were
      reviewed. There were 14 cases of Erb's palsy out of 11,484 vaginal deliveries
      (0.12%) and one case of Erb's palsy out of 2,874 cesarean deliveries. There was
      birth trauma (i.e., shoulder dystocia) noted at the time of delivery in eight
      cases (53.3%). However, a surprising finding was that in the other seven cases
      (46.7%) there was no evidence of shoulder dystocia at delivery. In the group in
      which Erb's palsy occurred and trauma was noted at the time of delivery, the
      average birth weight was 4,265 +/-480 g (range 3,550-5,110 g), with seven out of
      eight (88%) being large for gestational age (LGA). In the group in which Erb's
      palsy occurred but no trauma was noted at the time of delivery, the average birth
      weight was 2,906 +/- 745 g (range 1,590-3,950 g), with one out of seven (14%)
      being LGA. The infants without recognizable trauma weighed significantly less (P
      = 0.0009). In the group with trauma noted at delivery one out of eight (13%)
      received pitocin, and in the group without trauma noted at delivery one out of
      seven (14%) received pitocin. There was no significant difference in 5 min Apgar
      scores < 7 (3/8 vs. 0/7), umbilical cord pH (7.27 +/- 0.07 vs. 7.24 +/- 0.10), or
      base excess (-3.1 +/- 1.6 vs. -5.3 +/- 3.3) between those with recognizable
      trauma and those without recognizable trauma. The incidence of brachial plexus
      injury in this institution from 1987 to 1991 was 0.10%, which was unchanged from
      the incidence of 0.12% from 1954 to 1959, even though the cesarean rate rose from
      5% to 20% during this period. The appearance of Erb's palsy in the newborn may
      not be as closely linked to birth weight and recognizable birth trauma as has
      previously been thought. In this study half the cases of Erb's palsy occurred in
      normal-sized infants without trauma noted at delivery. The incidence of Erb's
      palsy in our population is similar to that of other reported studies and has
      remained unchanged over the past 30 years, even as our cesarean rate has risen
      from 5% to 20%.

PMID- 9029379
TI  - Renal tubular acidosis in pregnancy: case report and literature review.
AB  - Renal tubular acidosis is a rare form of chronic metabolic acidosis, which is
      either inherited as an autosomal dominant condition (Types 1, 2, and 3) or
      acquired. Its effects on pregnancy and vice versa are not known, but chronic
      acidosis may affect fetal bone growth and development. Chronic maternal acidosis
      may also lead to fetal distress, which should respond to correction of the
      maternal acidosis. The patient is a 20-year-old gravida 2, para 1-0-0-1, Hispanic
      female with distal renal tubular acidosis, diagnosed 1 year prior to this
      pregnancy after suffering from hypokalemic paralysis. During the pregnancy she
      required steadily increasing doses of potassium and bicarbonate, to maintain
      electrolyte balance. She delivered a healthy full-term female infant, weighing
      2,892 g, with Apgars of 5 and 9 at 1 and 5 min, respectively, following an
      induction of labor for oligohydramnios. There was no evidence of intrapartum or
      neonatal distress, and the infant was discharged home with her mother on the
      first postpartum day in good health. Established renal tubular acidosis, which
      was adequately treated with bicarbonate and potassium supplementation during
      pregnancy, had no apparent ill effects on fetal or neonatal well-being in this
      case.

PMID- 9029378
TI  - Recent advances in the management of preeclampsia.
AB  - The past decade has been characterized by few advances regarding the
      pathophysiology and prevention but many changes in the clinical treatment of
      patients with preeclampsia. Specifically, recommendations have been made for home
      or day-care management of a select group of patients with mild gestational
      hypertension or preeclampsia. Moreover, three randomized clinical trials revealed
      that expectant management with close monitoring of maternal and fetal conditions
      is possible in a select group of patients with severe preeclampsia at less than
      34 weeks' gestation. In addition, the efficacy of magnesium sulfate in the
      prevention and control of eclamptic convulsion has been validated in randomized
      controlled trials performed worldwide. In contrast, recent randomized trials
      failed to demonstrate any major benefit from the routine use of low-dose aspirin
      in pregnancy, whereas a recent meta-analysis found calcium supplementation during
      pregnancy to be effective in reducing the risk of hypertension.

PMID- 9029380
TI  - Management of thromboembolic disease associated with pregnancy.
AB  - Our objective was to identify practice patterns of members of the Society of
      Perinatal Obstetricians with regard to the management of thromboembolic disease
      in pregnant women. We sent survey-questionnaires to members of the Society of
      Perinatal Obstetricians and requested information on antepartum and postpartum
      management of four clinical case scenarios. We also requested information on the
      evaluation of hypercoagulability and on the dosing and monitoring of heparin
      during pregnancy. We received 515 responses after a single mailing (47%). Most
      respondents utilize some form of anticoagulation in pregnant women with a history
      of thromboembolic disease, although there was variation in the duration and
      intensity of anticoagulation. Nearly all respondents (96%) use full
      anticoagulation with heparin for pregnant women with prosthetic heart valves.
      Most respondents evaluate pregnant women for hypercoagulable disorders who
      present with a thromboembolism or have a history of thromboembolic disease. There
      is considerable variation with respect to the dosing and monitoring of heparin
      therapy during pregnancy. Although most SPO members recommend anticoagulation in
      pregnant women with a history of venous thromboembolism, there is marked
      variation in the intensity, duration, and monitoring of heparin therapy in
      pregnant patients. Randomized prospective studies are needed to establish
      accurate recurrence risks and to evaluate the efficacy of anticoagulation in
      pregnant women with a history of venous thromboembolism.

PMID- 9029381
TI  - A comparison of the 3 H glucose tolerance test and the 2 H value in identifying
      risk for excessive fetal growth.
AB  - The objective of this study was to determine if the 2 h value of the glucose
      tolerance test (GTT) is as reliable as the complete GTT in identifying risk for
      excessive fetal growth. Five hundred eighty-eight patients underwent a 3 h oral
      GTT at 26-28 weeks' gestation. The 2 h value of the test was compared to the
      results of the GTT. The incidence of large for gestational age (LGA) infants was
      compared for patients who had an abnormal GTT or an abnormal 2 h value only. A
      normal 2 h value was associated with a normal GTT in 98.5% of cases, while an
      abnormal 2 h value was associated with an abnormal GTT in 70% of cases. An
      abnormal GTT was associated with a 22% incidence of LGA, while a 2 h value > or =
      165 mgm/dl was associated with a 20% incidence of LGA. This difference was not
      statistically significant. A single 2 h value GTT is more cost-effective and as
      predictive as a complete 3 h GTT in identifying risk for excessive fetal growth.

PMID- 9029382
TI  - Pregnancy complicated by obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a well-recognized psychiatric disorder
      often beginning in reproductive age. A case of OCD in pregnancy is presented and
      its management discussed. A 28-year-old G3P2 woman presented at 8 weeks'
      gestation for prenatal care. She had been diagnosed with OCD following her prior
      pregnancy. Her symptoms primarily involved obsessions about infectious disease
      and compulsive cleaning and organization of household items, both of which
      greatly distressed her and interfered with caring for her children. She had been
      managed with clomipramine between pregnancies and was beginning a clinical trial
      of fluvoxamine when pregnancy was diagnosed. She discontinued medication when she
      realized she was pregnant. Her symptoms were managed during the pregnancy with
      frequent appointments with her obstetrician and her psychiatrist. She used a
      behavioral technique, "thought-stopping", as well. Her symptoms worsened in the
      last month of pregnancy and immediately after delivery; she delivered a normal
      infant. The clomipramine was restarted postpartum. She has done well since then,
      with minimal psychiatric symptoms. OCD is a disabling psychiatric disorder that
      occurs in women of reproductive age. With careful management, pregnancy without
      disabling psychiatric symptoms can occur.

PMID- 9029383
TI  - Mortality from early neonatal group B streptococcal sepsis: influence of
      obstetric factors.
AB  - Our objective was to determine if the neonatal mortality from early group B
      streptococcal (GBS) septicemia was associated with obstetric factors other than
      birthweight. Medical records from our institution for all neonates with positive
      blood cultures for GBS in the first 7 days of life between January 1981 and
      December 1992 were reviewed (n = 61). All the neonates had received broad
      spectrum intravenous antibiotics within 3 h of birth, and all had cerebrospinal
      fluid (CSF) cultures obtained. In a multivariate model we found a significant
      association between neonatal mortality and birthweight (P = .01). The other
      significant associations were with positive CSF cultures (P = .01) and
      intrapartum invasive fetal scalp electrode monitoring (P = .03). After
      controlling for these and other variables in the model, the odds of death for the
      infants with scalp electrode monitoring was 8 times greater (95% CI = 1.1,56),
      compared to those who had the GBS septicemia but no intrapartum fetal scalp
      electrode monitoring. In conclusion, the association we found between neonatal
      fatality from early GBS septicemia and invasive fetal scalp electrode monitoring
      is plausible and needs further study.

PMID- 9029385
TI  - Cord blood carbohydrate-deficient transferrin levels are markedly higher than
      maternal.
AB  - Regular, heavy alcohol intake results in transferrin that is deficient in
      carbohydrate moieties. Carbohydrate-deficient transferrin (CDT) has been used as
      a biologic marker of heavy alcohol exposure in nonpregnant humans. There have
      been no reports of CDT levels in pregnancy. Our objective was to determine
      maternal and cord blood levels of CDT. Parturients were recruited at delivery
      based on graded representative alcohol consumption, from abstainers to heavy
      drinkers, as determined by screeners skilled at eliciting drug and alcohol
      histories. Maternal and cord blood serum samples were obtained at delivery. A
      double antibody radioimmunoassay was used to determine CDT in each sample. There
      were 83 paired specimens analyzed by paired t tests and stepwise regression
      analysis. Cord blood CDT units/liter (44.0 +/- 29.5) were significantly (P <
      0.0001) higher than maternal (18.4 +/- 7.0). Maternal and cord CDT did not
      correlate with race, perinatal risk score, gestational age at delivery, birth
      weight, Apgar scores, or reported alcohol intake. Maternal CDT levels had a
      significant negative correlation with cigarette smoking. Cord blood CDT levels
      are significantly higher than maternal. While regular, heavy alcohol consumption
      by adults results in serum transferrin deficient in carbohydrate moieties, the
      reason for elevated fetal CDT is unknown.

PMID- 9029384
TI  - Hepatic transplantation during pregnancy and the puerperium.
AB  - Liver transplantation is the treatment of choice for many patients with acute and
      chronic hepatic failure. Although uncommon, hepatic failure may occur during
      pregnancy or after delivery, and liver transplantation may be life-saving. We
      report a case of a liver transplant performed during pregnancy in a patient with
      decompensated cirrhosis from chronic autoimmune hepatitis. A patient with chronic
      autoimmune hepatitis developed decompensated cirrhosis at approximately 18 weeks'
      gestation. Despite attempts at medical stabilization, her condition worsened, and
      an orthotopic liver transplant was performed at 23 weeks. The procedure was
      complicated by transient hypotension, and fetal death was diagnosed
      postoperatively. Her postoperative course was complicated by hypotension,
      infection, oliguric renal failure, anemia, thrombocytopenia, and rejection. She
      spontaneously labored on the 6th postoperative day and delivered without
      difficulty a 560-g stillborn male. The patient recovered and was discharged 31
      days after surgery on prednisone, tacrolimus, mycostatin, erythropoietin, and
      iron. Liver transplantation may be a valuable therapeutic option for treatment of
      pregnant or puerperal women with hepatic failure.

PMID- 9029386
TI  - Role of amniotic fluid in newborn acceptance and bonding in canines.
AB  - Maternal behavior, such as licking and cleaning of the newborn, and oral
      consumption of the placenta and membranes is characteristic of nearly all
      mammals. They are the first step toward maternal acceptance and bonding in
      canines. Factors affecting these initial behaviors are unclear. Also the impact
      of these initial behaviors in regard to establishing long-term newborn acceptance
      and bonding is unclear. We undertook this study to determine the role of the
      amniotic fluid on newborns and oral consumption of the placenta and membranes on
      the initial development of the maternal-newborn relationship. Thirty litters were
      studied, nine serving as controls in which the maternal and neonatal behaviors
      were simply observed for 36 h after delivery. Twenty-one litters underwent three
      different manipulations and served as the study groups. The first study group
      consisted of nine litters where the pups, placenta, and membranes were
      immediately separated from the mother at birth. Pups were washed three times and
      returned to the mother, and observation began. The second group of nine litters
      had the pups, placentas, and membranes immediately removed from the mother at
      birth. These pups were washed three times and returned to their mother. After 2.5
      h of observations, pups were bathed in their amniotic fluid and the placenta and
      membranes returned to mother. In the third study group, three litters had the
      pups immediately separated from their mother, washed only once, and returned to
      their mother. The placenta and membranes were removed permanently in this case.
      In the control group, acceptance of pups was universal. In the first study group,
      all pups were rejected for the entire 36 h of observation. In the second study
      group, all pups were rejected until they were bathed in amniotic fluid and the
      placentas returned to the mother. At this point, the mother accepted all pups. In
      the third study group, all pups were accepted by the mother during the entire
      observation period. It appears that having the amniotic fluid on pups is an
      important signal for the mother to begin licking, accepting, and establishing
      maternal bonding with the newborn in canines. In the absence of amniotic fluid on
      the pups, rejection for the first 36 h was universally present.

PMID- 9029387
TI  - Risk of recurrence of craniospinal anomalies.
AB  - The authors analyzed 1,655 situations from their Genetic Counseling Service over
      a 15 year period where the reason for counseling was craniospinal anomaly (neural
      tube defects and/or hydrocephalus) in the family. Excluding the obviously
      monogenically inherited cases, they investigated pregnancies undertaken after
      1,285 isolated and 177 multiple forms of craniospinal abnormalities. The
      recurrence rate of craniospinal defects was found to be 3.66%, which is about ten
      times higher than the general population risk, supporting the theory of the
      multifactorial threshold model in the inheritance of these anomalies. The
      recurrence risks of neural tube defects and of hydrocephalus were 3.47% and
      2.95%, respectively. The authors concluded that recurrence risk is mainly
      influenced by the pathoanatomic severity of the involved anomaly, the degree of
      relationship, and the number of affected relatives in the family. There is a
      positive correlation between the pathoanatomic severity of the anomaly in the
      proband and the offspring. At least in one-half of the cases the same type of
      anomaly was observed again in the offspring as in the proband. Attention is drawn
      to the fact that hydrocephalus (ventriculomegaly) is often manifested only in the
      second half of gestation. Therefore, performing ultrasound examination is
      strongly recommended not only at the 18th but at the 24th week of gestation, as
      well in pregnancies with a positive history of neural tube defects and/or
      hydrocephalus.

PMID- 9029388
TI  - Idiopathic granulomatous angiitis of the central nervous system in pregnancy: the
      first case report.
AB  - Idiopathic granulomatous angiitis of the central nervous system (IGANS) is a rare
      vasculitis primarily affecting the spinal cord and brain not related to any
      underlying systemic disease. Clinical manifestations range from simple headache
      to cerebral vascular accidents secondary to vascular occlusion. The management of
      a pregnancy complicated by multiple risk factors including underlying IGANS is
      reported. An expectant, empiric approach was adopted and resulted in excellent
      maternal and neonatal outcomes. The first report of the management of a pregnancy
      complicated by IGANS is presented. Underlying maternal IGANS may not necessarily
      represent an indication for pregnancy termination.

PMID- 9029389
TI  - Single dose cefazolin prophylaxis for postcesarean infections: before vs. after
      cord clamping.
AB  - The objective of this study was to test the hypothesis that 1 g of cefazolin
      administered preoperatively is no more effective than the same dose administered
      after cord clamping in preventing postcesarean infectious morbidity. Ninety
      consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks
      gestation were randomized by computer to receive 1 g of cefazolin intravenously
      preoperatively or after cord clamping in a double-blinded, placebo-controlled
      study. The 2 groups were compared for differences in maternal and neonatal
      demographics, and intrapartum and operative characteristics associated with
      postcesarean infection. Primary maternal outcome variables were endometritis or
      wound infection. Secondary outcomes included intra-abdominal abscess formation,
      septic pelvic thrombophlebitis, pneumonia, or urinary tract infection. Neonatal
      outcomes included sepsis screens, sepsis, pneumonia, and meningitis. Subjects
      were followed 6 weeks postoperatively for late complications. Subjects receiving
      cefazolin preoperatively or after cord clamping had similar maternal and neonatal
      demographics, and intrapartum and operative characteristics. One patient in the
      former group experienced both endometritis and wound infection. In the latter
      group, 2 wound infections and 1 case of endometritis occurred (P = 0.35). There
      were no secondary maternal infections. Two infants treated for pneumonia and 2
      other infants readmitted with febrile illnesses were born to mothers receiving
      cefazolin preoperatively. Overall, 8 neonates were evaluated for suspected sepsis
      and all had negative studies. Six of these infants' mothers received cefazolin
      preoperatively (P = 0.28). In conclusion, 1 gram of cefazolin preoperatively is
      no more effective than the same dose administered after cord clamping in
      preventing postcesarean infectious morbidity, but is associated with a trend
      toward increased suspected sepsis in the newborn. However, this trend may be
      related to differences between the study groups' risk factors for infection.

PMID- 9029390
TI  - Health technology assessment and the NHS R&D initiative.

PMID- 9029391
TI  - A portable system for monitoring physiological responses to hypoglycaemia.
AB  - Hypoglycaemia is the most common complication affecting people with Type 1
      insulin dependent diabetes mellitus. Its onset is characterized by symptoms which
      include sweating, tremor, palpitations, loss of concentration and tiredness. As
      part of a research project to investigate the mechanisms of hypoglycaemia we have
      developed an ambulatory system to monitor and record pulsatile changes in blood
      flow, pulse interval, body temperature and skin impedance. The system uses a
      pocket computer (Atari Portfolio) to collect and store the data on a memory card.
      The analogue system consists of two thermocouples, an infrared
      photoplethysmograph and skin impedance monitoring circuit. To conserve power the
      system is programmed to make measurements for 2 min every 10 min: using this
      regimen over 16 h of data can be stored. Data collected during a spontaneous
      overnight hypoglycaemic episode are presented and also a comparison between
      continuous and intermittent data collection during a period of induced
      hypoglycaemia. The system is being used to investigate the physiological
      responses to hypoglycaemia but could easily be adapted for monitoring other
      physiological signals.

PMID- 9029392
TI  - Monitoring progress after lung transplantation from home-patient adherence.
AB  - A paperless electronic spirometer/diary instrument has been employed in a home
      monitoring programme for lung and heart-lung transplant patients at the
      University of Minnesota. The monitoring programme is part of a long term study to
      develop a system which will detect the earliest signs of developing rejection or
      infection in the transplanted organs. It is based on patient daily self
      measurements of standard spirometry, vital signs, and symptoms recorded at home
      and transmitted weekly to the study data center over the telephone using a modern
      built into the instrument. This report summarizes adherence behaviour for 41
      subjects enrolled in the study over a 12 month period. The number of subjects
      from whom home data has been received each week was used to measure adherence at
      the subject level. The number of records received each week measured adherence at
      the daily recording level. A data record consists of a daily set of spirometry,
      vital signs, and symptom values from a given subject. Approximately 82% of
      subjects transmitted records each week, over the 52 week review period. There was
      an average of 4.5 records received each week from each subject. Transmitted
      records had missing vital sign or symptom items in less than 2% of cases,
      spirometry data was always present. This evaluation showed than lung transplant
      recipients are willing and able to use a home-monitoring instrument, and that
      basic spirometry, data entry, and data transmission can be performed
      satisfactorily.

PMID- 9029393
TI  - ECG data compression using Hebbian neural networks.
AB  - Principal component analysis has long been used for a variety of signal
      processing applications, including signal compression. Neural network
      implementations of principal component analysis provide a means for unsupervised
      feature discovery and dimension reduction. In this paper, we describe a method
      for the compression of ECG data using principal component analysis. Hebbian
      neural networks were used for principal components computation. A variety of
      examples of normal and pathological ECGs obtained from the MIT ECG database
      demonstrate that the proposed method can provide compression ratio up to 30 with
      PRD% less than 5%.

PMID- 9029394
TI  - A comparison of the hydrodynamical behaviour of three heart aortic prostheses by
      numerical methods.
AB  - The behaviour of the blood flow passing through artificial heart values in aortic
      position is numerically simulated by discretizing the Navier-Stokes equations for
      viscous incompressible flow through the finite element method. Three different
      artificial valves, Starr-Edwards, St Jude and disc valves, are modelled by using
      the finite element method as well as the Navier-Stokes equations for viscous
      incompressible flow. The blood flow behaviour is characterized by discretizing
      both planar and axisymmetric domains of the value devices. The streamlines as
      well as the velocity distributions are studied and compared. Likewise, the
      pressure patterns are analysed and compared. Some numerical examples of the three
      valves are presented and discussed herein.

PMID- 9029395
TI  - Occurrence and frequency of transmission of naturally occurring simian retroviral
      infections (SIV, STLV, and SRV) at the CIRMF Primate Center, Gabon.
AB  - Among the primates held at the CIRMF Primate Center, Gabon, no serological sign
      of SIV infection could be demonstrated in 68 cynomolgus monkeys, 60 chimpanzees,
      nine gorillas, and 12 sun-tailed monkeys, while seven of 102 mandrills and six of
      24 vervets were infected with SIV. Six mandrills, seven vervets and ten
      cynomolgus monkeys exhibited a full HTLV type 1 Western blot profile. The sera of
      two gorillas and one chimpanzee presented with a positive but not typical HTLV
      Western blot profile. The sera of the gorillas lacked p24 antibodies, and the
      chimpanzee had a Western blot profile evocative of HTLV-II. All attempts to
      amplify viruses from these animals by PCR were unsuccessful. Two other
      chimpanzees and seven gorillas presented with indeterminate HTLV Western blot
      profiles. In the mandrill colony, only male animals were STLV seropositive and no
      sexual transmission to females was observed. SIV infection was also more frequent
      in male than female mandrills and sexual transmission appeared to be a rare
      event. No SRV infection was observed in macaques.

PMID- 9029396
TI  - Prevalence of Epstein-Barr virus (EBV) antibodies in primate stocks of zoological
      gardens.
AB  - Examination of 387 serum samples from 41 primate species with two different
      ELISAs for the presence of IgG-antibodies against Epstein-Barr virus. Antibodies
      were detected in 15 out of 32 species of Old World primates and none in six
      species of New World primates by screening ELISA (Enzygnost, Behringwerke AG,
      Marburg), a testkit for human diagnostics. To avoid species-dependent factors
      which could influence the sensitivity of the Enzygnost assay, a competition ELISA
      was established. The modified test assessed antibodies in all species of Old
      World primates and three species of the New World primates.

PMID- 9029398
TI  - Fetal ultrasonography: normal biometric ranges in the baboon (Papio hamadryas).
AB  - Normal biometric ranges for fetal growth in a captive breeding baboon (Papio
      hamadryas) colony are described. Measurements include crownrump length,
      biparietal diameter, binocular distance, head circumference, abdominal
      circumference, femur length and amniotic fluid index. The pattern of fetal growth
      is compared with other baboon subspecies and man. The uses and limitations of
      such data for breeding colony management and optimum utilisation of
      experimentally derived data are discussed.

PMID- 9029397
TI  - Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of
      age and gender.
AB  - Measurement of bone turnover in conditions such as osteoporosis has been limited
      by the need for invasive iliac bone biopsy to reliably determine parameters of
      bone metabolism. Recent advances in the area of serum and urinary markers of bone
      metabolism have raised the possibility for noninvasive measurements; however,
      little nonhuman primate data exist for these parameters. The purpose of this
      experiment was to define the normal range and variability of several of the newer
      noninvasive bone markers which are currently under investigation in humans. The
      primary intent was to determine age and gender variability, as well as provide
      some normative data for future experiments in nonhuman primates. Twenty-four
      rhesus macaques were divided into equal groups of male and female according to
      the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years.
      Urine was collected three times daily for a four-day period and measured for
      several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline
      (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the
      lumbar spine were performed at the beginning and end of the study period. Serum
      was also obtained at the time of bone densitometry for measurement of osteocalcin
      levels by radioimmunoassay. There were no significant differences in bone mineral
      density, urine PYD, or urine DPD based on gender. Bone density was lowest in the
      youngest animals, peaked in the 15-20-year group, but again decreased in the
      oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely
      related pattern to bone density. The most important result was the relative age
      insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone
      density changes take months or years to become measurable and iliac biopsies are
      invasive, the PYD/DPD marker ratio may have important implications for rapid
      noninvasive measurement of the effects of potential treatments for osteoporosis
      in the non-human primate model.

PMID- 9029399
TI  - Identification of rhesus macaques with spontaneous endometriosis.
AB  - Rhesus macaques (Macaca mulatta) with endometriosis were identified using
      reproductive histories, serum levels CA-125, pelvic ultrasonography, laparoscopy,
      and histopathology. All animals were evaluated from a large breeding colony and
      had a history of infertility and/ or spontaneous abortions. Laparoscopy and
      ultrasonography were performed on 40 macaques: 27 macaques from the breeding
      colony with elevated CA-125 levels, ten macaques from the breeding colony with
      normal or low serum CA-125 levels, and three macaques from another facility with
      previously diagnosed spontaneous endometriosis. Clinical endometriosis was
      diagnosed by laparoscopy in 16/37 (43%) macaques from the breeding colony and was
      confirmed by histologic examination in all animals biopsied. The disease was
      classified as minimal (40%), mild (25%), moderate (10%), or severe (25%). The
      most common sites of endometriosis were the serosal surface of the uterus (75%)
      and the posterior cul-de-sac (75%). In this study, CA-125 levels were useful in
      identifying animals from the breeding colony with endometriosis. The rhesus
      macaque provides a valuable animal model to study endometriosis and potentially
      to assess efficacy of therapeutic agents for this disease condition.

PMID- 9029400
TI  - Macaque sperm fusion with zona-free hamster oocytes.
AB  - Semen from six cynomolgus macaques was washed twice by centrifugation in BWW
      media and resuspended in 1:2 (vol:vol) of Tes-Tris-buffered eggyolk extract (EXT)
      diluent and BWW (EXT-BWW). Caffeine and dbcAMP were added to induce capacitation.
      Sperm were treated with calcium ionophore, A23187, followed by the addition of
      EXT to recover motility, then washed into BWW. The percent motile sperm was
      similar in ionophore-treated and control sperm suspensions, but motility of
      treated sperm decreased significantly by 20 min after treatment. The percentage
      of viable, acrosome-reacted sperm was 56.3% following ionophore treatment versus
      4.0% in control suspensions. When ionophore-treated sperm were coincubated with
      zona-free hamster oocytes, 51% of oocytes had evidence of sperm fusion and no
      oocytes were penetrated after incubation with control sperm. These results are
      consistent with the hypothesis that macaque sperm are capable of fusion with zona
      free hamster oocytes if sperm are viable and acrosome-reacted.

PMID- 9029402
TI  - Uterine epithelioid leiomyosarcoma in a pig-tailed macaque.
AB  - During ultrasonographic examination following spontaneous abortion, an
      approximately 6-cm diameter mass of mixed echogenicity is detected in the uterine
      wall of a mature pig-tailed macaque (Macaca nemestrina). Grossly, the mass is
      associated with the uterine fundus, multilobulate and tan with red-black mottled
      foci on cut surface. Microscopically, the invasive mass is composed of poorly
      differentiated round cells arranged in sheets and bundles supported by a fine
      fibrous stroma. On immunohistochemical evaluation, neoplastic cells contain
      vimentin, desmin, muscle actin, and smooth muscle alpha-actin antigens and do not
      react with antibodies to low and high molecular-weight cytokeratins. Cell
      morphology and immunohistochemical results indicate a diagnosis of epithelioid
      leiomyosarcoma (clear cell variant).

PMID- 9029401
TI  - Nesidioblastosis associated with hyperglycemia in two squirrel monkeys (Saimiri
      sciureus).
AB  - Nesidioblastosis associated with progressive weight loss and hyperglycemia was
      diagnosed in two mid-adult, wild-caught, male squirrel monkeys (Saimiri
      sciureus). Hyperglycemia, glucosuria, and abnormal glucose tolerance test results
      were found when the monkeys were presented for clinical evaluation for chronic
      weight loss, episodic dehydration, hypothermia, and lethargy. Immunohistochemical
      studies of the pancreatic tissue demonstrated that the proliferating endocrine
      cells stained predominantly glucagon-positive in the most severely affected
      monkey.

PMID- 9029403
TI  - The physiological and behavioral effects of radio music on singly housed baboons.
AB  - The response of four singly caged baboons to radio music was measured using
      behavioral and physiological indices. Heart rate and blood pressure, measured
      through a tether system, as well as behavior, were recorded during a two-week
      period in which radio music was available in half of the samples. The behavior of
      the subjects, as well as their blood pressure, did not vary in relation to radio
      music. Heart rate was significantly lower when the radio was on.

PMID- 9029404
TI  - Influence of a potential anti-asthmatic drug, CR 2039, upon the anticonvulsive
      activity of conventional antiepileptics against maximal electroshock-induced
      seizures in mice.
AB  - CR 2039 [[4-(1H-tetrazol-5-yl)-N-(4-(1H-tetrazol-5-yl]phenylbenza m ide], in
      doses of 10, 50, and 100 mg/kg i.p., significantly elevated the threshold for
      electroconvulsions, increasing the CS50 (current strength 50% in mA) values from
      6.3 to 7.2, 7.5, and 7.6 mA, respectively. When combined with carbamazepine,
      diphenylhydantoin, or valproate, CR 2039 (5 and 10 mg/kg) potentiated the
      anticonvulsive action of these antiepileptics against maximal electroshock
      induced convulsions which was reflected by significant decreases in the
      respective ED50s (in mg/kg). The protective efficacy of phenobarbital was not
      affected by the phenylbenzamide derivative. The potentiation of the
      anticonvulsive activity of three antiepileptics was not accompanied by increased
      adverse effects, evaluated in the chimney test (motor coordination) and passive
      avoidance task (long-term memory). Finally, CR 2039 (10 mg/kg) did not alter the
      plasma levels of the antiepileptic drugs studied which speaks against a
      pharmacokinetic mechanism in the observed results. It is concluded that CR 2039
      may prove a safer anti-asthmatic drug for the use in epileptic patients than
      aminophylline which, either acutely or chronically, considerably impaired the
      anticonvulsive activity of conventional antiepileptics.

PMID- 9029406
TI  - Effect of ascorbate and cysteine on the 3,4-methylenedioxymethamphetamine-induced
      depletion of brain serotonin.
AB  - The extent of long-term depletion of serotonin (5-HT) produced by 3,4
      methylenedioxymethamphetmaine (MDMA) was assessed in rats treated with the
      antioxidants sodium ascorbate or L-cysteine. There was a 30-35% reduction in the
      striatal concentration of 5-HT 7 days following a single injection of MDMA (20
      mg/kg, s.c.). MDMA had no significant effect on striatal concentrations of 5-HT
      in rats that had been treated with ascorbate (250 mg/kg, i.p.) or cysteine (500
      mg/kg, i.p.) 30 min prior to and 5 hrs following the administration of MDMA.
      Treatment with ascorbate or cysteine did not alter the accumulation of MDMA in
      brain as determined by in vivo microdialysis. Moreover, neither ascorbate nor
      cysteine altered the stimulation of dopamine release elicited by MDMA. These data
      are supportive of the view that MDMA-induced toxicity of 5-HT neurons may be
      related to the production of free radicals and subsequent oxidative damage.

PMID- 9029405
TI  - Rat strain differences in the vulnerability of serotonergic nerve endings to
      neurotoxic damage by p-chloroamphetamine.
AB  - Substituted amphetamines are known to selectively destroy serotonin (5-HT) nerve
      endings in distant projection fields of the dorsal raphe nuclei and the systemic
      administration of these drugs is widely used in investigations of the role of the
      central 5-HT system and of the mechanisms involved in their toxicity. Until now
      Sprague-Dawley rats were almost exclusively used for this purpose and the
      findings were thought to apply to other strains as well. We compared the long
      term effects of the administration of different doses of para-chloroamphetamine
      (PCA) on three specific markers of the density of 5-HT presynapses, [3H]
      paroxetine binding to 5-HT-transporters, tryptophan hydroxylase apoenzyme
      contents, and 5-HT levels in the frontal cortex of Sprague-Dawley and Wistar
      rats. PCA-treatment caused a dose dependent decline of all three parameters which
      was much more pronounced in Sprague-Dawley compared to Wistar rats. An i.p. dose
      of 4 mg PCA/kg body weight, which caused a severe, about 90% reduction of all
      three parameters of 5-HT innervation in Sprague-Dawley rats was almost
      ineffective in Wistar rats. The dose of 8 mg/kg which was required to eliminate
      about 80% of cortical 5-HT presynapses in Wistar rats was already lethal to
      Sprague-Dawley rats. The reasons of this different susceptibility of the 5-HT
      system in the two rat strains are unknown. Their elucidation will contribute to a
      better understanding of inherited differences in individual vulnerability to the
      neurotoxic effects of substituted amphetamines. The combined measurements of
      transporter density, of tryptophan hydroxylase apoenzyme contents, and of 5-HT
      levels is a powerful tool for the assessment of experimentally induced changes in
      the density of 5-HT innervation in distant projection fields of the raphe nuclei.

PMID- 9029407
TI  - Pharmacological modifications in dopaminergic neurotransmission affect the
      quinpirole-evoked suppression of serotonin N-acetyltransferase activity in chick
      retina: an impact on dopamine D4-like receptors.
AB  - Dopamine (DA) plays an important role in the regulation of melatonin biosynthesis
      in retinas of several vertebrate species. In the retina of chick, the DA receptor
      controlling melatonin production represents a D4-like subtype. Stimulation of
      this receptor by quinpirole (QNP) results in a dose-dependent decline of the
      nighttime activity of serotonin N-acetyltransferase (NAT; a key regulatory enzyme
      in melatonin biosynthesis) and melatonin level of chick retina. The present study
      was undertaken to determine whether long-term treatment with antipsychotic drugs
      (clozapine-30 mg/kg, i.m.; sulpiride-100 mg/kg, i.m.; and raclopride-10 mg/kg,
      i.p., once daily for 21 days) and L-DOPA (80 mg/kg, i.p., once daily for 7 days)
      affects the response of the melatonin generating system of chick retina to the
      suppressive effect of QNP. Chronic administration to chicks of clozapine and
      sulpiride, but not raclopride, resulted in a markedly increased response of
      retinal NAT activity to the action of QNP. ED50 values for QNP were 3-times
      (clozapine) and 4-times (sulpiride) lower than those in the respective vehicle
      treated control groups. On the other hand, QNP was significantly less potent in
      retinas of birds treated with L-DOPA than in control animals; the ED50 value for
      QNP was 3-times higher in birds injected with L-DOPA than in the vehicle-treated
      group. These results indicate that long-term treatment with clozapine, sulpiride
      and L-DOPA may modify the reactivity of D4-like DA receptors regulating NAT
      activity of chick retina. A possibility of modifications of circadian and
      electrophysiological processes within the eye following prolonged administration
      of DA-ergic drugs is discussed.

PMID- 9029408
TI  - Regulation of N-terminus-deleted human tyrosine hydroxylase type 1 by end
      products of catecholamine biosynthetic pathway.
AB  - The N-terminal 52-, 70-, and 157-amino acids-deleted mutants and wild-type
      tyrosine hydroxylases were expressed in Escherichia coli and utilized to
      investigate the roles of the N-terminus in the catecholamine inhibition on enzyme
      activity. Their lysate's supernatants were used as enzyme samples. Three
      catecholamines, namely dopamine, norepinephrine, and epinephrine, affected both
      wild-type and mutant enzymes after preincubation in the mode of mixed inhibition,
      and the most marked alteration among the kinetic parameters produced by the
      deletion was the increase in the inhibition constants. The deletions also
      abolished the catecholamine-induced shift of the pH profile of the enzyme
      activity toward a more acidic pH optimum. All three mutants responded to
      catecholamines almost in the same way. These results suggest that the three
      catecholamine end products exert their inhibition on tyrosine hydroxylase to the
      same extent and that the N-terminal 52 amino acid residues contain the key
      sequence in mediating the inhibitory action.

PMID- 9029409
TI  - Lack of permanent nigrostriatal dopamine deficit following 6-hydroxydopamine
      injection into the rat striatum. Short communication.
AB  - The lesion caused by a single 6-hydroxydopamine injection into rat striatum was
      evaluated. In vivo positron emission tomography using a dopamine reuptake tracer
      revealed no consistent reduction in striatal dopamine transporter. Amphetamine
      rotation test was negative up to 18 weeks. A 21% reduction in striatal dopamine
      seen at 11 weeks was not detectable at 18 weeks. Tyrosine hydroxylase-positive
      neurone counts showed no decline in substantia nigra. Our results suggest that
      this lesion may be subject to compensation and therefore should be used with
      caution in studies on neuroprotective treatments of Parkinson' disease.

PMID- 9029410
TI  - Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian
      patients.
AB  - Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused
      by synthesis and accumulation of endogenous and exogenous toxins. Because of
      structural similarity to MPTP, beta-carbolines, like norharman and harman, have
      been proposed as putative neurotoxins. In vivo they may easily be formed by
      cyclization of indoleamines with e.g. aldehydes. For further elucidation of the
      role of beta-carbolines in neurodegenerative disorders harman and norharman
      levels in cerebrospinal fluid (CSF) were measured in 14 patients with PD and
      compared to an age- and sex-matched control group (n = 14). CSF levels of
      norharman and harman in PD were significantly higher compared to controls. These
      results may suggest a possible role of harman and norharman or its N-methylated
      carbolinium ions in the pathophysiological processes initiating PD. However the
      origin of increased levels of these beta-carbolines remains unclear. On the one
      hand one may speculate, that unknown metabolic processes induce the increased
      synthesis of harman and norharman in PD. On the other hand a possible impact of
      exogenous sources may also be possible.

PMID- 9029411
TI  - Depression in Parkinson's disease: biogenic amines in CSF of "de novo" patients.
AB  - INTRODUCTION: Etiology of depression in Parkinson's disease (PD) is associated
      with serotonergic dysfunction. Previous studies, supporting this hypothesis, were
      performed on patients treated with antiparkinsonian drugs. To eliminate the
      influence of parkinsonian drug therapy and to elucidate significance of different
      biochemical pathways in PD associated with depression we determined levels of
      biogenic amines in cerebrospinal fluid (CSF) of 26 untreated "de novo"
      Parkinsonian patients. MATERIAL AND METHODS: Patients were scored with the
      Hamilton depression scale (HD) and subdivided into groups with HD score > or = 18
      and HD score < 18. Diagnosis of depression was made according to DSM III R. Both
      groups were matched for age and motor disability. RESULTS: In both groups no
      significant differences appeared between CSF levels of dopamine, noradrenaline,
      3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4
      hydroxyphenylglycol and 5-hydroxyindole acetic acid, determined by high
      performance liquid chromatography. DISCUSSION: In contrast to previous studies on
      treated Parkinsonian patients no sign of altered serotonin metabolism especially
      in context with severity of depression in early stages of PD was found. Due to
      our results, we suggest, that biochemical markers of depression in CSF of PD may
      be influenced by antiparkinsonian therapy and that depression in PD may respond
      to serotonin reuptake inhibitors mainly in later stages of PD.

PMID- 9029413
TI  - CSF inositol does not predict antidepressant response to inositol. Short
      communication.
AB  - CSF inositol was reported to be reduced in depression and inositol has been
      reported to be effective in treatment of depression. We studied CSF inositol in
      18 drug-free depressed patients and 36 normal controls; the depressed patients
      then participated in an open trial of 18 gm daily inositol treatment for 4 weeks.
      There was no difference in pre-treatment CSF inositol between depressed patients
      and controls. CSF inositol levels did not predict response on the Hamilton
      Depression Scale to 4 weeks of inositol treatment.

PMID- 9029412
TI  - Human adenosine A2a receptor (A2aAR) gene: systematic mutation screening in
      patients with schizophrenia.
AB  - Several lines of evidence suggest an involvement of adenosine A2a receptor
      (A2aAR) mediated adenosinergic neuromodulation in the etiopathogenesis of
      schizophrenia. We therefore performed a systematic mutation scan of the complete
      coding region of the human A2aAR gene in a sample of 42 schizophrenic patients.
      We detected one rare naturally occurring receptor variant (Gly-340-Ser) and two
      silent mutations (405C/T and 1083C/T). To our knowledge the Gly-340-Ser
      substitution is the first naturally occurring molecular variant of the A2aAR
      identified. Determining the frequency of the three variants in 42 unrelated
      healthy controls, we observed a significant trend towards an overrepresentation
      of the 1083T variant in patients when compared to controls (p = 0.041). This
      trend was followed up in a large independent replication sample. However, we were
      not able to confirm the original trend in the second sample (p = 0.367). The Ser
      340 variant was found in a single schizophrenic individual. Investigation of the
      patient's family revealed independent segregation between the Ser-340 variant and
      psychiatric illness. Our data suggest that genetically determined structural
      variation of the A2aAR does not play a major role in the development of
      schizophrenia.

PMID- 9029415
TI  - Graduate education in nursing: beyond essentials.

PMID- 9029414
TI  - A preliminary study of possible psychoactive effects of intravenous forskolin in
      depressed and schizophrenic patients. Short communication.
AB  - Forskolin is a unique activator of adenylate cyclase that bypasses membrane
      receptors and directly raised levels of the second messenger cyclic AMP.
      Depressed patients and schizophrenic patients with negative symptoms have been
      reported to have reduced cyclic AMP levels. In the first study of forskolin in
      psychiatry, we gave iv forskolin in a 75 minute infusion to four depressed and
      five schizophrenic patients. All four depressed patients showed a transient mood
      elevation or stimulation, as did two of the five schizophrenic patients.

PMID- 9029416
TI  - Characteristics of graduate adult health nursing programs.
AB  - This descriptive study explored the current characteristics and emphases of
      graduate programs which offer adult health nursing curricula. All NLN-accredited
      master's programs offering the adult health focus were requested to send selected
      demographic information and materials/bulletins normally sent to prospective
      students. The Conrad and Pratt model for curriculum decision-making was used to
      organize results related to environmental input and curriculum design variables.
      Descriptive statistics were employed to analyze admission requirements, types of
      study permitted, length of program, type of courses (core, electives/cognates,
      specialty) and completion requirements. Results indicated that adult health
      graduate programs have multi-tracks. Students were generally attending part-time.
      Full-time study completion time was four to six semesters. Evening and one day
      per week offerings were frequently found, as were numerous innovative strategies.
      Prevalent admission requirements were: graduation from an NLN-accredited BSN
      program, current licensure, specified GPA, GRE scores, health assessment and
      statistics courses, professional references and possible personal interview. Most
      programs required core courses in theory/conceptual frameworks, issues, roles,
      statistics and research. Electives/cognate courses and thesis/non-thesis options
      were present in most programs.

PMID- 9029417
TI  - Spiral processes of becoming: women's experiences within the context of doctoral
      education.
AB  - The purpose of this qualitative study was to explore women's experiences of being
      a doctoral student. We report on interviews from 11 women, 8 of whom were
      Caucasian and 3 of whom were African-American. Participants in the study
      described their experiences as doctoral students in ways that reflected a
      spiraling process of becoming. This process included experiences of confidence,
      support and self-discovery. This research has implications for nursing faculty
      and women engaged in doctoral education as well as for women who anticipate
      entering doctoral programs.

PMID- 9029418
TI  - Epigenesis of the nurse practitioner role revisited.
AB  - In the mid-1970s, an article discussed the identity crises of nurse practitioner
      (NP) students which occurred during their educational experience. This article
      noted that NP students progress from dependence to interdependence and
      demonstrate regression, anxiety and conflict. Twenty years later we have also
      observed these changes in our own graduate students. This article describes our
      observations, analyzes them with respect to well-known developmental theory, and
      offers suggestions for teaching methodologies which enhance successful
      transitions through the crises.

PMID- 9029419
TI  - Agricultural safety and health: principles and possibilities for nursing
      education.
AB  - Health risks for the men, women and children involved in production agriculture
      are substantial. The profession of nursing, with its current emphasis on health
      promotion and disease prevention, is potentially capable of profoundly impacting
      the health of these vulnerable families in positive ways. Suggestions for methods
      of integrating content and activities related to agricultural safety and health
      in already crowded nursing curricula are offered.

PMID- 9029420
TI  - Developmental care in advanced practice neonatal nursing education.
AB  - Neonatal nursing education for the future is being influenced by two forces:
      expanding knowledge of infant development and health care reform. In response to
      the former and in anticipation of the latter, the University of Colorado School
      of Nursing incorporated developmentally based, family-centered care concepts in
      its recent revision of the master's program in neonatal nursing.

PMID- 9029421
TI  - A conceptual model for an adult health masters in nursing curriculum.

PMID- 9029422
TI  - Telephone interviews: a cost-effective way to select faculty.
AB  - The telephone interviewing process was a very positive experience for the
      interviewers. It gave us the opportunity to collaborate together to determine how
      best to represent our own peers and find future peers. With minimal expense, it
      expedited the process of filling our positions. The efficiency and thoroughness
      of the interview process allowed us to fill the positions by holding only three
      on-campus interviews which were shorter (less than one day in length in one case)
      and within budgetary allotments.

PMID- 9029423
TI  - Use of meta-analysis as a teaching strategy in nursing research courses.
AB  - In order to become knowledgeable consumers of nursing research, nursing students
      must be able to critically read research and determine the study's value for
      nursing practice. As the number of nursing intervention studies rises and
      research topics are studied more extensively, the use of meta-analysis in the
      discipline of nursing will also increase. The same scientific rigor demanded of
      other types of research must be applied to meta-analysis. In this article two
      teaching strategies using meta-analysis are shared for sharpening both
      undergraduate and graduate nursing students' critiquing skills. On the
      undergraduate level, nursing students can assess the quality of the studies
      included in a particular meta-analysis. On the graduate level, students can use
      an appraisal checklist of criteria for evaluating the actual meta-analysis.

PMID- 9029424
TI  - Advanced education for the role of rural nurse generalist.
AB  - The Montana State University College of Nursing has developed a master's degree
      program which prepares nurses as generalists with advanced knowledge for
      understanding and addressing rural health care needs. The programs is clear about
      its goals and objectives and does not attempt to be "all things for all people."
      The emphasis is on rural nursing, and this emphasis is present in recruiting,
      teaching, research and publication at the College. Classroom and clinical
      experiences challenge students to develop a broad range of skills, and most
      importantly to enhance critical thinking and problem-solving abilities. Since
      delivering high quality health care in rural areas requires the ability to
      understand health care from the consumer's perspective, both data collection and
      clinical experience in rural communities are required. The enthusiasm for rural
      nursing--practice, teaching and research--displayed by faculty members, alumnae
      and students is both a major factor in, and an indication of, the program's
      success.

PMID- 9029425
TI  - Elevated beta 2-microglobulin after nephrectomy.

PMID- 9029426
TI  - Methylene chloride, carboxyhemoglobin and cardiac risk.

PMID- 9029427
TI  - Neurophysiological effects of flickering light in patients with perceived
      electrical hypersensitivity.
AB  - An increasing number of people in Sweden are claiming that they are
      hypersensitive to electricity. These patients suffer from skin as well as
      neurological symptoms when they are near computer monitors, fluorescent tubes, or
      other electrical appliances. Provocation studies with electromagnetic fields
      emitted from these appliances have, with only one exception, all been negative,
      indicating that there are other factors in the office environment that can effect
      the autonomic and/or central nervous system, resulting in the symptoms reported.
      Flickering light is one such factor and was therefore chosen as the exposure
      parameter in this study. Ten patients complaining of electrical hypersensitivity
      and the same number of healthy voluntary control subjects were exposed to
      amplitude-modulated light. The sensitivity of the brain to this type of visual
      stimulation was tested by means of objective electrophysiological methods such as
      electroretinography and visual evoked potential. A higher amplitude of brain
      cortical responses at all frequencies of stimulation was found when comparing
      patients with the control subjects, whereas no differences in retinal responses
      were revealed.

PMID- 9029428
TI  - Development, use, and evaluation of clinical practice guidelines.
AB  - The development and use of practice guidelines, if framed as recommendations for
      best practices in the prevention, diagnosis, treatment, and management of
      occupationally related health concerns and disability, can improve the quality of
      occupational medical practice and worker health and well being. Adherence to
      guidelines should improve the efficiency and effectiveness of prevention, care,
      and disability management by reducing the present wide variance in practices and
      then by moving the mean or median of process and outcome statistics toward
      recommended levels. The information developed for guidelines can also be used for
      patient discussion and expectation management. Practicing in evidence-based,
      agreed-upon ways should also make occupational medical practices more defensible.
      Guidelines should be explicit, be based on a review of the available evidence and
      benefits vs risks, have clear medical logic, link findings to diagnosis to
      treatment ot prevention, be time-based, and avoid recommending unproven
      approaches as a last resort. If possible, they should be reviewed and tested for
      usability. Guidelines that start with common occupational health concerns are
      best suited to prevention and outpatient care, because patients present in this
      way. The contents of a useful occupational health guideline would include a
      statement of purpose and scope, the method of development; the authors' and
      reviewers names and affiliations; an analysis of the specificity, sensitivity,
      and predictive power of mechanisms of illness or injury, symptoms, signs and
      tests; findings that point to a serious or emergent condition requiring immediate
      referral or treatment; diagnostic criteria; and initial treatment, including work
      with the patient in a therapeutic partnership. The guideline should also present
      information on factors known to be associated with work, and predictors of
      delayed recovery. Disability-duration statistics and methods of matching job
      requirements with worker abilities are also helpful. Guidelines should then
      outline reassessment of those patients whose health concerns remain after a
      reasonable recovery period. The recommendations should again be evidence-based
      and conform to the other attributes listed above. A discussion of management
      after reassessment, including behavioral referral, further testing, and
      procedures, is also quite useful. Recommendations for restoration of function and
      return to work complete guidelines focused on diagnosing, treating, and resolving
      activity limitations among workers. Simply developing and publishing guidelines
      has not resulted in improvement in practice. However, if used as the basis for
      peer-group interactions and actions by occupational health opinion leaders,
      guidelines can contribute to marked improvements in quality, worker satisfaction,
      and worker health.

PMID- 9029429
TI  - A descriptive study of recurrent low back pain claims.
AB  - This is the first large-scale study of US workers that describes the demographic
      and cost differences between recurrent and nonrecurrent low back pain (LBP)
      disability claimants, using data from a large workers' compensation insurer.
      Persons with at least one LBP claim in 1990 and one or more additional claims in
      1990 to 1996 were defined as recurrent. Persons with at least one LBP claim in
      1990 but no subsequent claims were defined as nonrecurrent. Fourteen percent of
      claimants were recurrent. The percentage of recurrent claimants who were male
      (77.2%) was higher than the percentage that were female (22.8%). This difference
      was more pronounced in the younger age groups. The median total cost for
      recurrent LBP claims in 1990 was 4% greater than for nonrecurrent 1990 LBP
      claims, whereas the mean cost was 48% less. Most studies of LBP recurrence among
      US workers have followed single-corporation employees. Our rate of recurrence was
      lower than these previously reported rates. However, analysis of independent
      workers' compensation insurance company data may provide a more accurate
      assessment of LBP claim recurrence among US workers.

PMID- 9029430
TI  - Incidence of non-fatal workplace assault injuries determined from employer's
      reports in California.
AB  - Although fatal work-related assault assault injury rates are routinely reported
      in the United States, reports of non-fatal injuries are not routinely examined.
      Non-fatal workplace assault injuries can be reported through many agencies. One
      of the most common reporting mechanisms in California is the Employer's Report of
      Occupational Illness and Injury. Employer's Reports filed from October 1, 1994
      through January 31, 1995 in the state of California were the source of workplace
      assault information for this study. All reports indicating an assault-related
      injury were identified and characterized by gender and occupation of the victim,
      type of assault and weapon used, and industry. Annual rates were determined based
      on the number of estimated annual reports and the civilian working population.
      The estimated annual rate of workplace assault injuries for California based on
      Employer's Reports is 72.9 per 100,000 workers, which is approximately 50 times
      the fatal rate. Rates differed by industry, with retail, hospital, transportation
      and police workers exhibiting the highest rates. Assaults were predominantly Type
      I, which involve criminal activity, and Type II, which involve an assault by a
      client, patient, or inmate. The rates of non-fatal work-related assault injury
      are much greater and have different characteristics than fatal injuries. These
      non-fatal injury patterns need to be considered when estimating the burden of
      assault injuries on businesses, and can help identify the most effective
      prevention strategies.

PMID- 9029431
TI  - Repeated case-control studies as a method of surveillance for asthma in
      occupations.
AB  - Our aim was to establish whether the case-control design may be applied in
      surveillance for occupational asthma. In a region with intensive manufacturing
      industries, we carried out one case-control study from 1974 to 1978 and another
      from 1989 to 1993; 325 and 387 pairs of cases of asthma and of age- and sex
      matched control subjects, respectively, were selected. Current risks were found
      to be higher than past estimates for painters, farmers, millers/bakers, textile,
      wood/ furniture, and chemical workers. High risks for asthma have recently
      appeared in leather, polyurethane plastics, hospital and food industry workers,
      welders, and shoemakers. It is concluded that the case-control approach may be
      used to describe variations in asthma risk by occupational categories and time. A
      method to measure the efficiency of the diagnostic process for occupational
      asthma is also proposed.

PMID- 9029432
TI  - Blood lead levels in radiator repair workers in Colorado.
AB  - A laboratory-based blood lead surveillance system in Colorado identified radiator
      repair workers as having the highest blood lead levels of all worker groups
      reported. A survey of 42 radiator repair shops in ten locales throughout Colorado
      was undertaken to estimate the prevalence of workers with elevated blood lead
      levels > 25 micrograms/dL. The survey was designed to test the sensitivity of the
      surveillance system and to assess working conditions and practices in the
      radiator repair industry in Colorado. Of 63 workers, 39 (62%) had blood lead
      levels > 25 micrograms/dL. The sensitivity of the surveillance system for
      detecting radiator repair workers with elevated blood lead levels was estimated
      at 11%. None of the radiator repair shops had adequate local exhaust ventilation.
      Work practice and engineering modifications are needed to reduce lead exposure in
      this industry.

PMID- 9029433
TI  - Treating work stress: an alternative to workers' compensation.
AB  - Work stress is a growing and expensive problem. A model for group psychotherapy
      for disgruntled workers presenting with psychiatric symptoms was offered through
      Kaiser Permanente's outpatient psychiatry department. The findings of a 2-year
      follow-up study conducted on group participants indicate that this type of
      cognitive-behavioral group psychotherapy can be helpful in increasing employee
      satisfaction and adjustment at work. This also raises the possibility that early
      intervention through group psychotherapy may be effective in reducing the
      incidence of workers' compensation stress claims.

PMID- 9029434
TI  - Musculoskeletal-related disability in US Army personnel: prevalence, gender, and
      military occupational specialties.
AB  - Research on military populations indicates that musculoskeletal-related disorders
      represent a prevalent source of outpatient visits, lost work time,
      hospitalization, and disability. Despite the increasing role of women in the
      military, little is known regarding the association among military occupations,
      gender, and disability. The study presented here analyzed 41,750 disability cases
      to determine: (1) prevalence of work-related musculoskeletal disability, (2)
      specific jobs associated with greater risk of musculoskeletal disability, and (3)
      association among gender, job-type, and disability. Results indicate: (1) back
      related disorders represent the most prevalent sources of disability, (2) certain
      occupations were associated with higher disability risk, (3) women experienced
      higher overall, and musculoskeletal, disability risk, and (4) specific jobs were
      identified in which women experienced higher rates of musculoskeletal disability.
      These findings highlight the need to consider the interaction between workplace
      factors and gender on disability in the military work force.

PMID- 9029435
TI  - Atriopeptin lowers aqueous humor formation and intraocular pressure and elevates
      ciliary cyclic GMP but lacks uveal vascular effects in the bovine perfused eye.
AB  - The effects of atriopeptin (AP) on intraocular pressure (IOP), aqueous humor
      formation (AHF) and ciliary cyclic GMP in bovine eyes perfused in vitro through a
      ciliary artery were investigated. AHF was monitored fluorophotometrically by
      perfusing the anterior chamber with Barany's mock aqueous humor containing
      fluorescein. To study the effect of AP on cyclic GMP synthesis, eyes were
      injected with an intra-arterial bolus of AP prior to dissection of the ciliary
      processes. For comparison, individual ciliary processes, or isolated ciliary
      epithelial cells were incubated with AP. Cyclic GMP was extracted by
      homogenization, aqueous partition and column chromatography, and measured by
      radioimmunoassay (RIA). Decreases in IOP or AHF were seen approximately 15 min
      after the injection of AP and persisted throughout a 60-80 min perfusion.
      Arterial perfusion pressure was not significantly altered by AP, even when
      vascular tone was raised by adding noradrenaline to the perfusate. In whole eyes,
      ciliary cyclic GMP increased in response to AP. Cyclic GMP in isolated ciliary
      processes, or cultured ciliary epithelial cells incubated with AP also increased.
      We conclude that the decrease in IOP in the bovine eye by AP is due to a
      reduction in AHF, which is independent of any vascular effect. Ciliary cyclic GMP
      may be the intracellular mediator involved.

PMID- 9029436
TI  - Effects of pilocarpine and other antiglaucoma drugs on cultured human Tenon's
      fibroblast cells.
AB  - It has been found that long-term therapy with topical antiglaucoma drugs may
      decrease the success of glaucoma filtering surgery. In this study, various
      antiglaucoma drugs, including carteolol, betaxolol, levobunolol, pilocarpine, and
      timolol, were investigated for their proliferative effect on cultured human
      Tenon's fibroblast cells. It was found that the 3H-thymidine uptake of cultured
      fibroblast cells was inhibited by commercial antiglaucoma drugs, including
      carteolol of 0.1% concentration (13%), 0.01% (50%) and 0.001% (53%), betaxolol of
      0.05% concentration (14%), 0.005% (42%) and 0.0005% (62%), levobunolol of 0.05%
      concentration (2%), 0.005% (32%) and 0.0005% (55%), and timolol of 0.025%
      concentration (4%), 0.0025% (47%) and 0.00025% (55%), whereas the 3H-thymidine
      uptake was increased by commercial pilocarpine eyedrop from 103% (0.2% of
      concentration), 170% (0.02% of concentration) to 171% (0.002% of concentration),
      when cells were treated with commercial drugs for 100 min. Meanwhile, the
      proliferations of cultured fibroblast cells were stimulated by simultaneously
      combining 0.2%, 0.02% and 0.002% concentrations of pilocarpine eyedrops with
      other antiglaucoma drugs, such as carteolol of 0.1% concentration (50%), 0.01%
      (113%) and 0.001% (138%), betaxolol of 0.05% concentration (24%), 0.005% (128%)
      and 0.0005% (142%), levobunolol of 0.05% concentration (32%), 0.005% (87%) and
      0.0005% (119%), and timolol of 0.025% concentration (15%), 0.0025% (94%) and
      0.00025% (118%). Following incubation with pure pilocarpine, the proliferation of
      Tenon's fibroblast cells was inhibited for 84% (0.2% concentration), 84% (0.02%
      concentration) and 90% (0.002% concentration). When fibroblast cells were treated
      with commercial pilocarpine eyedrops for 24 hours, the 3H-thymidine uptake was
      increased to 160% (0.02% concentration) and 172% (0.002% concentration). This
      result shows that the commercial pilocarpine may play a crucial role for the
      proliferation of cultured human Tenon's fibroblast cells.

PMID- 9029438
TI  - Effect of collagen cross-linking in collagen corneal shields on ocular drug
      delivery.
AB  - It is well known that some ocular diseases can be treated more effectively with a
      collagen shield containing drug. The influence of collagen cross-linking on drug
      delivery is not known. We determined if collagen cross-linking affects ofloxacin
      bioavailability at three different collagen shield dissolution times. In this
      study, the collagen shields were not impregnated in drug but an eye drop was
      simply instilled after application of collagen shield. A non-cross-linked
      collagen shield, with a dissolution time of 12 h, disappeared more rapidly from
      the rabbits' eyes due to proteolysis after application in vivo. On the other
      hand, the cross-linked collagen shields, with dissolution times of 24 and 72 h,
      served as an ofloxacin depot and enhanced topical ofloxacin penetration into the
      cornea and the aqueous humor. As the dissolution times for the cross-linked
      collagen shield are longer than those of the non-cross-linked type, they serve as
      drug reservoirs. Therefore, cross-linked collagen shields might be useful ocular
      drug delivery devices because they can allow drug concentrations to achieve
      higher levels in the cornea and aqueous humor.

PMID- 9029437
TI  - Ocular absorption, blood levels, and excretion of dorzolamide, a topically active
      carbonic anhydrase inhibitor.
AB  - Dorzolamide is a powerful inhibitor of carbonic anhydrase (CA) II that penetrates
      the sclera and cornea to reach the ciliary process and lowers formation of HCO3
      and aqueous humor. The usual dose applied to the eye in treatment of glaucoma is
      1 drop (30 microL of 2% solution) every 8 hr to each eye, or a total daily dose
      of 4 mg. On this regime, the red cells accumulated drug over a period of 8 days,
      reaching a value of 20-25 microM, which corresponds to the concentration of CA II
      in human red cells. This drug concentration persisted throughout the 18 months of
      application. The plasma concentration was 0.034 microM, or 1/700 that of the red
      cells. This plasma concentration corresponds to that calculated from the dilution
      of administered drug into body water. The data are well fitted into the
      equilibrium expression for KI of dorzolamide against CA II at 37 degrees C, as 8
      x 10(-9) M. The red cells also contain a small amount (5 microM) of the N-des
      ethyl metabolite, probably reflecting its modest binding to CA I. In the initial
      8-day drug period, virtually none appeared in the urine since CA II sites were
      being filled. At steady state, renal excretion was 1.3 mg/day and the renal
      clearance 90 ml/min. These excretion numbers include the small (20%) amount of
      the des-ethyl metabolite of dorzolamide. The relation of these data to lowering
      of intraocular pressure is clear. By the systemic route, an inhibitor such as
      acetazolamide is effective when free drug concentration in plasma is 2.5 microM.
      In the case of topical drugs, as shown here, the plasma concentration is some 100
      x lower, but the concentration in ciliary process is 2-10 microM, comparable to
      that following systemic drugs (1). In conclusion, the concentration in plasma
      (reflecting free drug) of dorzolamide is about 1/200 of that needed for systemic
      effects as seen following acetazolamide or methazolamide. Thus, there is a clear
      pharmacological basis for the lack of any physiological effects of ocular
      dorzolamide, except on the eye itself.

PMID- 9029439
TI  - Penetration into the anterior chamber via the conjunctival/scleral pathway.
AB  - The importance of the conjunctival/scleral pathway as a route of entry into the
      ciliary body, and in particular uptake and deposition by vessels, was
      investigated. A constant concentration of methazolamide analogs as well as 6
      carboxyfluorescein (6-CB) and rhodamine B (RB) was maintained on either the
      cornea or the conjunctiva/sclera tissue, the latter excluding the cornea. The
      solutions were applied with the use of a cylindrical well affixed to the cornea
      of an anesthetized white rabbit. After two hours, concentrations of drug or dye
      were measured in cornea, aqueous humor or iris/ciliary body for both routes of
      entry. Confocal microscopy methods were used to determine reflected fluorescence
      images for 6-CB and RB. Carbonic anhydrase inhibition, partitioning, solubility
      and intraocular pressure (IOP) measurements were also determined. Permeability
      calculations were estimated for drug diffusing against aqueous flow within the
      posterior chamber. The conjunctival/scleral route of entry produced higher
      iris/ciliary body concentrations for all compounds except for the lipophilic RB.
      Confocal microscopy results suggested that drug is gaining entry into the ciliary
      body through vessel uptake in the sclera. Following entry of drug into the
      conjunctival/scleral tissue, a significant portion enters scleral vessels and
      deposits within the ciliary body. Calculations are given that indicate that once
      drug penetrates the cornea it is highly unlikely drug diffuses through the pupil
      against aqueous flow to enter the posterior chamber and reach the ciliary body.

PMID- 9029440
TI  - The effectiveness of 0.5% atropine in controlling high myopia in children.
AB  - Twenty highly myopic children (> or = -6.0 D) were treated with 0.5% atropine
      eyedrops once per night. Twelve subjects were initially treated with a short
      acting cycloplegic agent, tropicamide (0.5%) (Group A), and the other eight
      subjects did not receive any myopic therapy before atropine (Group B). These
      cases were followed for up to five years. In Group A, the mean myopic progression
      rate after 0.5% atropine treatment was -0.01 +/- 0.04 D/M (Diopter/Month), which
      was significantly lower than that of the period during tropicamide treatment (
      0.12 +/- 0.09 D/M) (p < 0.05). In Group B, the mean myopic progression rate after
      atropine therapy was begun was -0.04 +/- 0.06 D/M, which was also significantly
      slower than that of non-medication, -0.14 +/- 0.07 D/M (p < 0.05). The results
      suggested that 0.5% atropine is effective for slowing down myopic progression,
      even in highly myopic children.

PMID- 9029442
TI  - Experimental electroretinographic exploration of retinal ischemia: preventive use
      of free radical scavengers and anti-PAF agents.
AB  - Electroretinographic exploration is an effective approach to evaluate retinal
      function. In order to investigate physiopathological mechanisms and evaluate
      potentially protective therapies for retinal ischemia, we developed three
      experimental models: the first two on isolated retina, with ischemia induced by
      either stopping perfusion or clamping the ophthalmic artery, and the third, in
      vivo, with ischemia induced by ocular hypertonia. Since free radicals are
      implicated in the formation of post-ischemic lesions, we evaluated the protective
      effects of drugs known to be free radical scavengers and of an immunomediator
      antagonist, an anti-PAF (platelet activating factor) agent.

PMID- 9029441
TI  - Facilitation of retinal function recovery by coumarin derivatives.
AB  - Ischemic retinopathy is a difficult disease to treat, although numerous drugs
      have been tried in the clinics. Coumarin was one of those tried as an anti
      coagulant with a marginal efficacy. In this study, 15 coumarin derivatives were
      studied on the b-wave recovery in electroretinogram which is an indicator of the
      functional recovery of retina after ischemic insult. It was found that when
      positions 6, 7 and 8 were occupied by various functional groups, the b-wave
      recovery could be markedly enhanced. On the other hand, single occupation of
      position 3 with any functional group would cause damaging effects to the anti
      ischemic activity. It is concluded that some coumarin derivatives with two or all
      of these positions at 6, 7 and 8 occupied by certain functional groups could
      result in useful drugs for the treatment of ischemic retinopathy.

PMID- 9029443
TI  - Protection against light-induced retinal degeneration with naftidrofuryl
      (Praxilene) in the rat.
AB  - The purpose of this work was to investigate the ability of Naftidrofuryl
      (Praxilene, Lipha-Sante, France) to produce light-induced retinal degeneration in
      the rat. Fisher male rats were injected intraperitoneally with 30 mg/kg
      Naftidrofuryl in 0.9% NaCl. The first injection took place 30 minutes before the
      beginning of the constant light exposure (90 fc) and was repeated at days 2 and
      4. The animals were sacrificed at day 7. Controls treated or not with
      Naftidrofuryl were exposed to a regular cyclic light environment (20 fc). Eyes
      were fixed in 4% paraformaldehyde and embedded in Historesin. Whole median 5
      microns sections of the retina were analyzed by measurement of the thickness of
      the retinal photoreceptor nuclear and inner and outer segment layers with a
      Biocom image analyzer. After one week of constant illumination, the photoreceptor
      nuclear layer thickness decreased in all regions of the retina, more in the
      superior than in the inferior region. In animals treated with Naftidrofuryl, a
      significant rescue from degeneration was observed throughout all retinal regions.
      An average rescue of 66% (compared with the retina from constantly illuminated
      rats) was observed. Naftidrofuryl had no effect on cyclic light-raised rats.
      Naftidrofuryl partially protects against the degeneration of photoreceptors
      induced by constant light illumination of the rat retina.

PMID- 9029444
TI  - Oral carriage of Helicobacter pylori: a review.
AB  - Helicobacter pylori is a microaerophilic, motile bacterium, especially adapted to
      life in the human stomach. The presence of H. pylori in the stomach is strongly
      associated with chronic gastritis and ulcer disease and is a risk factor for
      gastric cancers. The microorganism may be transmitted orally and has been
      detected in dental plaque, saliva, and feces, but the hypothesis that oral
      microflora may be a permanent reservoir of H. pylori is still controversial. A
      review of the literature suggests that the recovery of H. pylori in the mouth is
      probably intermittent, associated with gastroesophageal reflux but not with
      specific oral disease. Nonetheless, the PCR identification of oral H. pylori may
      become helpful, particularly in cases of gastritis or ulcer relapse after
      antimicrobial therapy. Eradication of oral H. pylori by local medication or
      periodontal procedures would rely on the precise identification of its ecological
      niche. Within family groups, prophylactic methods should be practiced to avoid
      oral carriage of H. pylori. The risk of iatrogenic transmission during dental
      care, however, is already circumscribed by standard professional hygiene
      procedures.

PMID- 9029445
TI  - Positive correlation between blood cyclosporin A level and severity of gingival
      overgrowth in rats.
AB  - Cyclosporin a is a drug used to control rejection of organ transplantation and
      autoimmune diseases; however, it has also been implicated in gingival overgrowth.
      The present study investigates the relationship between severity of gingival
      overgrowth and blood cyclosporin A (CsA) levels in Fischer rats treated orally
      with CsA. Thirty-six 15-day-old male rats were divided into six experimental
      groups and given powdered rat chow containing 0, 50, 100, 200, 300, and 400
      micrograms CsA/g diet ad libitum for 40 days. At the end of the 40-day treatment
      period, whole blood samples were collected from each rat for assessment of CsA
      levels. The rats were then sacrificed and the gingival sulcus depth
      (pseudopocket) around mandibular molars measured to estimate gingival overgrowth.
      The blood levels of CsA in rats increased with increasing amounts of CsA provided
      in their food. A 100% incidence in gingival overgrowth was induced in all the
      rats treated orally with CsA. The overgrowth was more severe in buccal than in
      lingual gingiva. A significantly positive correlation was found between gingival
      sulcus depth and the blood CsA level (rs = 0.914, P < 0.0001; Spearman's
      correlation coefficient by rank). On histological examination, the overgrown
      gingiva consisted of a thickened epithelial layer and an accumulation of
      subepithelial fibrous connective tissue components without marked distortion of
      their proportion.

PMID- 9029446
TI  - Alveolar bone loss in rats infected with a strain of Prevotella intermedia and
      Fusobacterium nucleatum isolated from a child with prepubertal periodontitis.
AB  - Prevotella intermedia and fusobacterium nucleatum are associated with various
      forms of periodontal disease. The purpose of the present study was to infect the
      clinical isolates of these periodontopathic bacteria and to induce a significant
      loss of alveolar bone in specific pathogen-free (SPF) rats in the absence of
      ligatures. P. intermedia YKD8 and F. nucleatum YKZ5 were isolated from a
      prepubertal periodontitis patient, while P. gingivalis MWB13 was from a patient
      with juvenile periodontitis. At first, SPF Sprague-Dawley rats (70 days of age,
      male) were infected with A. viscosus Ny1R and subsequently superinfected with P.
      gingivalis MWB13, P. intermedia YKD8, or F. nucleatum YKZ5, respectively. The
      control group was infected with A. viscosus Ny1R alone. All rats were killed and
      periodontal bone levels were assessed morphometrically 135 days after the first
      infection with A. viscosus. P. intermedia YKD8 was recovered frequently from
      rats, with serum antibody levels remaining highly elevated throughout the
      experiment. Significant loss of alveolar bone was found in rats infected with P.
      intermedia YKD8, the virulence of which was equivalent to that of P. gingivalis
      MWB13. F. nucleatum YKZ5 also induced alveolar bone loss, but not significantly
      when compared with rats infected with A. viscosus Ny1R alone.

PMID- 9029447
TI  - Occurrence of Porphyromonas gingivalis, Bacteroides forsythus, and Treponema
      denticola in periodontally healthy and diseased subjects as determined by an
      ELISA technique.
AB  - The aim of this study was to assess by means of an ELISA technique, the
      occurrence of 3 putative periodontopathogens, Porphyromonas gingivalis,
      Bacteroides forsythus, and Treponema denticola, in 3 clinically-defined adult
      periodontal conditions. Thirty systemically-healthy subjects were selected and
      grouped into 3 categories according to their periodontal health: 1) 10
      periodontitis subjects (PS), having moderate adult chronic periodontitis; 2) 10
      untreated gingivitis subjects (UGS), exhibiting no signs of periodontal
      destruction but presenting with clinical signs of mild gingivitis; and, 3) 10
      treated gingivitis subjects (TGS), having the same clinical status as UGS, but
      who received a thorough prophylaxis treatment within the past 7 to 14 days prior
      to the baseline examination. A total of 60 samples were collected subgingivally
      from the six Ramfjord teeth per subject in each group and ELISA analysis was
      carried out to give a semiquantitative estimate of P. gingivalis. B. forsythus,
      and T. denticola. The immunologic detection method suggested the presence of
      antigens of P. gingivalis, B. forsythus, and T. denticola in subjects from each
      of the 3 groups. When a global analysis for the 3 disease groups was performed at
      one time, statistically significant differences were found among the ELISA scores
      of the 3 bacterial species. For example, comparisons of the ELISA scores showed
      that the concentrations of P. gingivalis differed significantly when comparing
      TGS to UGS and PS, but not when examining UGS/PS. The ELISA scores for B.
      forsythus were significantly different between TGS and PS. Mean concentrations of
      T. denticola were significantly different when comparing PS to TGS or UGS,
      whereas no difference was found between the latter categories. Within the limited
      scope of this study, the concentration of antigens detectable from putative
      periodontopathogens like P. gingivalis, B. forsythus, and T. denticola differed
      among the 3 diseased groups, with periodontitis subjects often showing the
      greatest level of antigens. Thus, it is reasonable to expect that, when using
      sensitive immunological detection methods, antigens of suspected periodontal
      pathogens can be found irrespective of the individual's clinical status. However,
      while detectable in the periodontal sites, the concentrations of these
      microorganisms are most likely to be above the threshold necessary to induce
      clinically-significant disease. Studies with larger sample size and standardized
      antigens are necessary to determine if the groups we found not to differ, were,
      in fact, different.

PMID- 9029449
TI  - Sustained local delivery of chlorhexidine in the treatment of periodontitis: a
      multi-center study.
AB  - The safety and efficacy of a degradable, subgingivally placed drug delivery
      system containing 2.5 mg chlorhexidine (CHX) were evaluated in a randomized,
      blinded, multi-center study of 118 patients with moderate periodontitis. A split
      mouth design was used to compare the treatment outcomes of scaling and root
      planing (SRP) alone with the combined use of SRP and the CHX in pockets with
      probing depths of 5 to 8 mm. The two maxillary quadrants were used for the two
      treatment arms of the study. Scaling and root planing was performed at baseline
      only, while the CHX was inserted both at baseline and at 3 months. Clinical and
      safety measurements including probing depth (PD), clinical attachment level
      (CAL), and bleeding on probing (BOP) as well as gingivitis, plaque, and staining
      indices were recorded at baseline, and at 1, 3, and 6 months. The average PD
      reduction in the CHX-treated sites was significantly greater than in the sites
      receiving SRP alone at both 3 and 6 months with a mean difference of 0.42 mm (P <
      or = 0.01) at 6 months. The reduction in CAL at the treated sites was greater
      than at the SRP sites, although the difference was statistically significant at
      the 6-month visit only. An analysis of patients with initial probing depths of 7
      to 8 mm (n = 56) revealed a significantly greater reduction in PD and CAL in
      those pockets treated with CHX compared to SRP at both 3 and 6 months. The mean
      differences between test and control sites at 6 months were 0.71 mm and 0.56 mm
      PD and CAL respectively.

PMID- 9029448
TI  - The association between estrogen status and alveolar bone density changes in
      postmenopausal women with a history of periodontitis.
AB  - While numerous studies have demonstrated a relationship between 17-beta-estradiol
      (E2) deficiencies and skeletal bone loss in postmenopausal females, the influence
      of E2 deficiency on alveolar bone resorption is poorly understood. The purpose of
      this study was to examine the association between the estrogen status of
      postmenopausal women and alveolar bone density changes in a 1-year longitudinal
      study. Twenty-four postmenopausal women, within 7 years of menopause, were
      divided into 2 groups, E2-sufficient (n = 10) and E2-deficient (n = 14). Venous
      blood samples were taken at baseline, 6 months, and 1 year for radioimmunoassay
      determination of serum E2 levels. At baseline and 1 year, 4 vertical bite-wing
      radiographs were taken for computer-assisted densitometric image analysis
      (CADIA). Areas of interest (AOIs) for CADIA were crestal and subcrestal regions
      of posterior interproximal alveolar bone. Serum E2 levels were significantly
      higher at all 3 time points in the E2-sufficient subjects (P < 0.002), repeated
      measures ANOVA). Overall, mean CADIA values (0.30 +/- 0.07 for the E2-sufficient
      women and -0.44 +/- 0.07 for the E2-deficient women) were statistically different
      between groups (P < 0.001, repeated measures ANOVA), indicating that the E2
      sufficient women displayed a mean net gain in alveolar bone density and the E2
      deficient women displayed a mean net loss in alveolar bone density. Furthermore,
      the E2-sufficient women exhibited a higher frequency of sites demonstrating a
      gain in alveolar bone density, while the E2-deficient women exhibited a higher
      frequency of sites demonstrating loss in alveolar bone density. These data
      suggest that estrogen status may influence alveolar bone density changes as
      demonstrated with CADIA.

PMID- 9029450
TI  - Fusobacterium nucleatum T18 aggregates human mononuclear cells and inhibits their
      PHA-stimulated proliferation.
AB  - In previous studies Fusobacterium nucleatum has been shown to induce either
      stimulatory or inhibitory effects on human mononuclear cells. We examined the
      interaction of human mononuclear cells with human and cynomolgus monkey strains
      of F. nucleatum. Peripheral blood mononuclear cells (PBMCs) isolated from normal
      donors were aggregated in the presence of cells of F. nucleatum but not control
      bacteria. The aggregation of PBMCs and F. nucleatum T18 was inhibited by either L
      arginine, L-lysine, or pretreatment of the bacterial cells with heat, but was
      unaffected by the presence of sugars or normal human serum. Strain T18 aggregated
      purified T-cells and monocytes at approximately equal concentrations. When F.
      nucleatum T18 was incubated with PHA-stimulated PBMCs, DNA synthesis in the PBMCs
      was significantly inhibited and detection of IL-2R alpha on the PBMCs was
      reduced. These studies indicate that F. nucleatum aggregates PBMCs, and that this
      interaction is associated with both an inhibition of PBMC proliferation and a
      decrease in IL-2 receptor expression. The ability of F. nucleatum to inhibit
      mononuclear cell proliferation may be significant in the pathogenesis of
      periodontal diseases.

PMID- 9029451
TI  - The effectiveness of an aerosol reduction device for ultrasonic scalers.
AB  - Intraoral use of ultrasonic scalers may generate aerosols that contain infectious
      microorganisms and therefore pose a hazard to the health of the dental
      professional. The purpose of this in vivo study was to determine if an aerosol
      reduction device for an ultrasonic scaler would be effective in reducing the
      amount of contaminated aerosols produced during ultrasonic instrumentation.
      Twelve adult subjects participated in the study. A split-mouth design was
      utilized, and two treatments (in separate rooms) were performed on each subject:
      1) ultrasonic scaling for 5 minutes with the aerosol reduction device; and 2)
      ultrasonic scaling for 5 minutes without the aerosol reduction device. The right
      or left side of the subject's mouth was randomly assigned to one of the two
      treatment groups. After instrumentation, the subject and operator remained
      motionless for 25 minutes during collection of aerosol particles. Air samples
      were collected on blood agar plates 6 inches from the subject's mouth. Replicate
      organism detection and counting plates were used to sample microorganisms present
      on the investigator's face shield. All plates were incubated for 3 days at 37
      degrees C. The results, using the paired t-test (P < 0.001), indicate that the
      ultrasonic scaler without the aerosol reduction device had a significantly
      greater quantity of mean colony forming units (CFUs) 6 inches from the subject's
      mouth (45.1 +/- 28.9) than the ultrasonic scaler with the aerosol reduction
      device (2.6 +/- 3.6). No significant difference was evident in the number of CFUs
      found on the investigator's face shield. These data suggest that an aerosol
      reduction device is effective in reducing the number of microorganisms generated
      during ultrasonic scaling, therefore decreasing the risk of disease transmission.

PMID- 9029452
TI  - The vasculature in chronic adult periodontitis: a qualitative and quantitative
      study.
AB  - Blood vessel features in periodontal pocket soft tissues may be significant in
      the pathogenesis and progression of chronic periodontitis. The aim of this study
      was to make a quantitative histological assessment of the vasculature in soft
      tissue biopsies from patients with chronic adult periodontitis and patients with
      healthy periodontal tissues. We have also investigated changes in tissue
      morphology at both the histological and ultrastructural level. Twelve interdental
      biopsies were obtained, 6 from chronic adult periodontitis patients and 6 from
      healthy volunteers. The specimens were sliced, fixed in 3% glutaraldehyde,
      postfixed in 1% buffered osmium tetroxide, dehydrated, and embeded in araldite.
      One micron semithin sections were differentially stained with a dichromatic
      technique. The number of blood vessels (BV) for sub-epithelial, superficial and
      deep connective tissue layers were then assessed. Only in the sub-epithelial
      connective tissue layer was there a significant increase in the number of blood
      vessels (95% Confidence interval [CI]) in the chronic adult periodontitis
      specimens when compared to healthy specimens. The results of this study seem to
      indicate that a dichromatic staining technique facilitates the identification and
      quantification of blood vessels in epoxy resin embedded specimens at light
      microscope level, and that there is an increase in the number of blood vessels in
      the chronic adult periodontitis lesions.

PMID- 9029453
TI  - Experimental peri-implant tissue breakdown around hydroxyapatite-coated implants.
AB  - This study monitored experimental peri-implant tissue breakdown around
      hydroxyapatite (HA)-coated titanium dental implants. Thirty-two HA-coated
      cylindrical implants, in groups of two, were bilaterally inserted in the
      posterior maxilla and mandible in 4 Macaca mulatta monkeys. Two months after
      healing-abutment connection, a 2-month plaque control program was initiated.
      Clinical and radiographic recordings and peri-implant submucosal microbial
      samples were then obtained (baseline). Cotton ligatures were next placed around
      the healing-abutments and plaque control measures were abandoned. Clinical and
      radiographic recordings were repeated at 5 and 10 months post-baseline. Microbial
      samples were repeated at 10 months post-baseline, and ligatures were removed.
      Clinical, radiographic, and microbial examinations were again repeated at 11
      months post-baseline. Mean modified plaque index (mPI; P < 0.01), gingival index
      (G]; P < 0.01), and bleeding on probing (BOP; P < 0.05) scores increased over the
      plaque accumulation period. The mPI, and GI scores decreased after ligature
      removal (P < 0.001). Mean probing depth (PD) and clinical attachment level (AL)
      increased between baseline and the 5- and 10-month examinations (delta PD 3.0 mm;
      delta AL 2.7 mm; P < 0.05). PD values were reduced following ligature removal (P
      < 0.05). AL values and BP scores remained unchanged. A significant negative
      correlation was found between induced defect depth and width of keratinized
      mucosa at baseline (P = 0.03). At baseline, the submucosal microbiota was
      dominated by coccoid cells. Following ligature placement, the microbiota included
      a large proportion of Gram-negative anaerobic rods, predominantly Porphyromonas
      gingivalis, Bacteroides forsythus, and Fusobacterium species as well as beta
      hemolytic streptococci. Ligature removal had a limited effect on the composition
      of the submucosal microbiota. This non-human primate study indicates that
      ligature-enhanced plaque accumulation is a precursor of progressive peri-implant
      tissue breakdown around HA-coated implants. The associated microbiota resembles
      that of peri-implantitis and destructive periodontal disease in humans. This
      preclinical model may be useful to study modalities aimed at arresting peri
      implant tissue breakdown and at regeneration of bone in peri-implantitis defects.

PMID- 9029454
TI  - A correlation study of inflammatory cell mobilization in response to subgingival
      microbial colonization.
AB  - This study evaluated site-by-site the relations between subgingival microbial
      colonization and gingival tissue reactions. Experimental, deep periodontal
      defects were established at buccal surfaces of mandibular and maxillary canine
      teeth in 5 beagle dogs. The root surfaces were instrumented by a flame-shaped,
      fine-grained, rotating diamond point, or by a sharp curet. Following a 10-day
      postsurgical healing period, the dogs were fed a plaque-inducing diet for 70
      days. The animals were then sacrificed and tissue blocks of the experimental
      sites including teeth and periodontal tissues were secured. The buccal gingiva
      was removed and processed for histomorphometric analysis while the teeth were
      prepared for scanning electron microscopic evaluation of the extent of
      subgingival microbial colonization. The results revealed that inflammatory cell
      density in the junctional epithelium and in the connective tissue were positively
      correlated to subgingival microbial colonization (P < 0.01). Furthermore, the
      degree of significance decreased with increasing distance from the plaque. The
      present study demonstrates that a close relation may exist between the extent of
      subgingival microbial colonization and inflammatory gingival tissue reactions.

PMID- 9029456
TI  - Minocycline-induced intraoral pharmacogenic pigmentation: case reports and review
      of the literature.
AB  - Minocycline, a semi-synthetic tetracycline antibiotic, is well documented as
      being associated with pharmacogenic pigmentation of various tissues in humans and
      other mammals. The most obvious of these are skin pigmentation, but intraorally
      include "green" roots of erupted teeth, "black" roots of extracted teeth, a dark
      stain of the crowns of fully developed teeth, and "black" alveolar bone. This
      article presents five cases of "black" alveolar bone with photographic
      documentation of its progress. It also reviews the available English language
      literature on this phenomenon. The incidence of minocycline staining of alveolar
      bone is probably 2% of that population taking the drug for 2 months or longer.
      Presently, minocycline is most widely used in the young adult population for the
      treatment of acne. With the recent interest in minocycline as a palliative
      treatment for rheumatiod arthritis, an entirely different population could be
      experiencing this effect. If minocycline use becomes widespread as a treatment
      for rheumatoid arthritis, it is likely that more practitioners will be asked to
      diagnose this sometimes striking, though apparently benign, condition.
      Recognition of this condition will save the practitioner and the patient from
      unnecessary concern and surgery.

PMID- 9029455
TI  - Phenytoin and cyclosporine A specifically regulate macrophage phenotype and
      expression of platelet-derived growth factor and interleukin-1 in vitro and in
      vivo: possible molecular mechanism of drug-induced gingival hyperplasia.
AB  - Phenytoin (pht) is an anticonvulsant drug commonly used for the prevention of
      seizures. A common side effect of PHT therapy is gingival hyperplasia,
      occasionally so severe that it requires surgical intervention. Cyclosporine A
      (CSA) is a drug widely used for the control of rejection phenomena following
      solid organ and bone marrow transplantation. A frequent side effect of CSA
      administration is gingival overgrowth. As yet, the molecular mechanisms of drug
      induced gingival hyperplasia are unknown although it has been postulated that
      certain drugs increase fibroblastic activity through alterations in levels of
      various growth factors and cytokines. The purpose of this study was to: 1)
      evaluate monocyte/macrophage platelet-derived growth factor (PDGF) and
      interleukin (IL)-1 beta production in vitro after exposure to CSA; 2) determine
      the levels of PDGF-B and IL-1 beta gene expression in minimally inflamed gingival
      tissues of control patients and PHT-treated patients exhibiting gingival
      overgrowth as well as patients with severe gingival inflammation; and 3) combine
      characterization of macrophage phenotype with clinical presentation and
      expression of PDGF-B and IL-1 beta in gingival tissues from the control and PHT
      treated patients. For the in vitro studies, commercial ELISA kits were used to
      measure PDGF-A/PDGF-B and IL-1 beta levels in conditioned media from rat and
      human monocyte/macrophage cell cultures. CSA caused a significant elevation of
      PDGF but did not cause any changes in IL-1 beta levels. For the in vivo studies,
      quantitative competitive reverse transcription polymerase chain reaction (QC
      RTPCR) techniques were utilized to measure PDGF-B and IL-1 beta mRNA levels in
      experimental groups. PHT-treated patients exhibiting gingival overgrowth
      demonstrated a significant increase in PDGF-B mRNA compared with minimally
      inflamed controls. Patients with severe gingival inflammation also demonstrated a
      significant increase in PDGF-B mRNA however, PHT-induced PDGF-B upregulation is
      approximately 6 times larger than PDGF-B upregulation produced by inflammation
      alone. PHT-treated patients exhibiting gingival overgrowth demonstrated no
      significant increase in IL-1 beta mRNA; however, IL-1 beta mRNA levels in the
      severely inflamed gingival samples demonstrated a significant increase.
      Additionally, for the clinical samples, macrophage phenotype was characterized
      immunohistochemically in adjacent sections using specific monoclonal antibodies
      for inflammatory and reparative/proliferative phenotypes. There were no
      significant differences in the numbers of either macrophage phenotype in
      minimally inflamed gingival tissues; however, in the severely inflamed tissue,
      there was a significant increase in the inflammatory macrophage phenotype and in
      the hyperplastic gingival tissue, there was a significant increase in the
      reparative/proliferative macrophage phenotype. The results of this investigation
      indicate that the clinical presentation of inflamed and hyperplastic gingival
      tissues is associated with specific macrophages phenotypes which express the pro
      inflammatory cytokine IL-1 beta in inflamed tissues or the essential polypeptide
      growth factor PDGF-B in PHT-induced hyperplastic tissues.

PMID- 9029457
TI  - The effect of plaque retention on cyclosporine-induced gingival overgrowth in
      rats.
AB  - The purpose of this study was to examine the role of plaque retention on
      cyclosporine A (CsA)-induced gingival overgrowth. Forty-five male Sprague-Dawley
      rats, 15 for each of three CsA dosage conditions, were unilaterally ligated
      around the first mandibular molar (plaque retention). The silk ligature was left
      in place for 6 weeks. Contralateral first molars served as unligated controls.
      The daily dosage of CsA, administered by gastric feeding, was 0, 3, or 10 mg/kg
      body weight. Stone models from biweekly impressions of the molar sites were used
      to investigate development of gingival overgrowth. Rats were sacrificed at 6
      weeks for histopathological and histometric examination of the molar sites.
      Gingival overgrowth was significantly increased in sites with higher CsA dosage,
      longer treatment duration, and ligation. Gingival overgrowth was enhanced in
      ligated sites regardless of CsA dosage. However, the odds ratio of ligated over
      unligated sites for gingival overgrowth increased with increasing CsA dosage. The
      histopathological and histometric examination revealed significantly increased
      gingival volume in ligated sites in CsA-treated animals. The tissue enlargement
      included both the epithelium and the connective tissue; however, the epithelium
      to connective tissue ratio remained unaltered. Within limitations of the study,
      we suggest that plaque retention magnifies CsA-induced gingival overgrowth; thus,
      dental plaque appears to be a cofactor in the development of CsA-induced gingival
      overgrowth.

PMID- 9029458
TI  - A multicenter longitudinal clinical trial of a new system for restorations.
AB  - STATEMENT OF PROBLEM: A new method for fabrication of crowns and fixed partial
      dentures (Procera system) that involves electric discharge machining and copy
      milling has been developed. The metal used is unalloyed titanium, which can be
      processed as a single coping or multiple units joined to a pontic by laser
      welding. PURPOSE: The single-unit coping or the fixed partial denture (FPD)
      substructure is then veneered with a low-fusing porcelain. MATERIAL AND METHODS:
      In this article the clinical application of this technique was evaluated by six
      major universities in the United States. A total of 114 patients participated in
      this study, which involved 126 restorations (55 maxillary and 71 mandibular
      prostheses). There were 179 abutments, of which 73 were crowns and 53 were three
      unit FPDs. Surface and color, anatomic form, and margin integrity were assessed 1
      month after cementation and at 1 year with the California Dental Association
      (CDA) quality assessment evaluation system. RESULTS: No statistically significant
      differences in CDA scores between the 1 month evaluations and the 1 year
      assessments were found for surface and color (p = 0.68), anatomic form (p >
      0.99), or margin integrity (p = 0.57). By use of the lowest ranking in the three
      categories as the overall quality of the restoration, only 3.3% (two crowns and
      two FPDs) were not acceptable at the 1-month visit and 4.5% (two crowns and three
      FPDs) were not acceptable at the 1-year evaluation. At-the 1-month visit 96.6%
      (114) of the restorations were considered to be satisfactory, whereas 95.5% (107
      restorations) were evaluated similarly at the 1-year evaluation. CONCLUSIONS: The
      Procera system demonstrated, by use of the CDA criteria, its capability to
      produce quality prostheses that were rated satisfactory more than 95% of the time
      after insertion and maintained this high rating at least for 1 year.

PMID- 9029459
TI  - Adhesion of glass ionomer cement to a ceramometal alloy.
AB  - STATEMENT OF PROBLEM: Glass ionomer cements can be used for restoring minor
      caries lesions, sealing an endodontic access, and repairing defective margins of
      inlay-onlay restorations. Little information is available on the adhesion between
      ceramometal alloys and various types of glass ionomer cements. PURPOSE: The aim
      of this study was to determine whether the adhesion of glass ionomer cement to
      the surface of a ceramometal alloy could be enhanced with pretreatment of the
      alloy surface. MATERIAL AND METHODS: Six groups of five specimens were either
      ground with a diamond bur, sandblasted with aluminum oxide, or ground with a
      silicon-carbide stone before bonding to either conventional glass ionomer or
      resin-glass ionomer cements. Resistance to bond failure was tested with a three
      point loading test. RESULTS: The results revealed that the greatest resistance to
      bond failure was obtained by the resin-glass ionomer cement to the sandblasted
      alloy surface and the least resistance by the glass ionomer cement to the diamond
      ground alloy surface (p < 0.001). Both the type of glass ionomer cement (p =
      0.002) and the type of mechanical treatment (p = 0.001) affected the resistance
      to bond failure. CONCLUSIONS: This study suggests that pretreatment of alloy
      surfaces with a sandblasting device may be recommended when repairing marginal
      defects of alloy restorations with glass ionomers. Resin-glass ionomer cements
      seem to give better adhesion than conventional glass ionomer cements do.

PMID- 9029461
TI  - Comparison of the clinical abrasion resistance of six commercially available
      denture teeth.
AB  - PURPOSE: Clinical abrasion of denture teeth has certain implications when
      dentures are worn in excess of the average useful lifetime. The purpose of this
      study was to evaluate clinical denture tooth wear over a period of 3 years.
      MATERIAL AND METHODS: The wear of six commercially available denture teeth
      (Premierdent, Acrotone, vitapan, Rx1, Duravite, and Ivoclar Orthosit) and a
      seventh combination of teeth was compared. Seventy patients with complete
      dentures were divided into seven groups of 10 each to form the study population.
      RESULTS: There were no significant differences among the commercial denture
      teeth. Porcelain/Vitapan teeth exhibited the highest amount of abrasion.
      Significant wear was also measured between the Ivoclar Orthosit and
      Porcelain/Vitapan teeth.

PMID- 9029460
TI  - Influence of dentinal adhesives and a prefabricated post on fracture resistance
      of silver amalgam cores.
AB  - PURPOSE: Failures of silver amalgam cores for endodontically treated teeth have
      been attributed to the use of posts. The use of adhesive agents has been reported
      to improve the strength of silver amalgam restorations. The purpose of this study
      was to test the effects of two adhesive agents on the fracture resistance of
      silver amalgam cores with and without a post. MATERIAL AND METHODS: Sixty
      mandibular molars were restored with the use of silver amalgam, with or without
      one of the adhesive agents and/or a tapered prefabricated post. A universal
      testing machine, with a constant load rate of 0.5 mm/minute, was used to
      determine the force in kilograms at failure. RESULTS: The use of either adhesive
      agent with silver amalgam significantly increased the force at failure, and
      neither adhesive agent was significantly better than the other. Silver amalgam
      with a post and without an adhesive agent had the least resistance to fracture.
      CONCLUSIONS: The results indicated that endodontically treated mandibular molars
      restored with silver amalgam are more resistant to fracture when an adhesive
      agent is used.

PMID- 9029462
TI  - Cement-retained versus screw-retained implant restorations: achieving optimal
      occlusion and esthetics in implant dentistry.
AB  - STATEMENT OF PROBLEM: Optimal occlusion and esthetics are goals in prosthetic
      treatment. Implant dentistry is no exception. PURPOSE OF ARTICLE: The purpose of
      this article is to discuss how the choice to use screw-retained or cement
      retained implants dramatically influences the occlusion and esthetics.

PMID- 9029463
TI  - A stent for presurgical evaluation of implant placement.
AB  - This article describes a method of fabricating a stent with barium sulfate and
      stainless steel tubes for the accurate radiographic evaluation of the
      relationships of the predesigned superstructure, the scheduled implant placement,
      and the anatomic structure. The barium sulfate in the stent depicts the outline
      of the predesigned superstructure, and the stainless steel tubes indicate the
      intended location and inclination of the implants on the computed tomographic
      scans. In addition, this stent can be used as a surgical stent to guide the pilot
      drill to the desired site.

PMID- 9029464
TI  - Tooth intrusion in implant-assisted prostheses.
AB  - STATEMENT OF PROBLEM: Numerous reports and surveys have been published on natural
      tooth abutment intrusion with implant-connected fixed partial dentures. The
      consensus of these publications was that the cause of intrusion was
      multifactorial, with causative factors such as disuse atrophy, debris impaction,
      impaired rebound memory, and mechanical binding. It was also believed that the
      process was irreversible. PURPOSE: In this article, the limitations with these
      theories are discussed, and two patient reports of tooth intrusion reversal are
      reviewed. A review of the current literature is discussed, as well as the current
      theory of tooth movement in response to dynamic mechanical stimulus, a brief
      discussion of current experimental procedures and results, and the current
      recommendations for reversal of intrusion.

PMID- 9029465
TI  - Temporomandibular disorders, headaches, and neck pain after motor vehicle
      accidents: a pilot investigation of persistence and litigation effects.
AB  - STATEMENT OF PROBLEM: There is a lack of long-term follow-up studies that involve
      post-motor vehicle accident temporomandibular disorders and compensation. PURPOSE
      OF STUDY: The purposes of this retrospective pilot study were (1) to assess
      patients who had previously been treated for temporomandibular disorders after
      motor vehicle accidents to determine the nature of their symptoms in terms of
      jaw, head, and neck pain and jaw dysfunction and (2) to determine whether there
      was a difference in the pain and dysfunction between those who had settled and
      those who had not settled their insurance claims. MATERIAL AND METHODS: Thirty
      previously treated patients with temporomandibular disorders after motor vehicle
      accidents were questioned by telephone regarding litigation status and current
      jaw, head, and neck pain and jaw dysfunction symptoms. They did not differ
      substantially from a smaller group who were not able to be interviewed.
      Descriptive statistics were calculated and statistical tests were performed. A
      total of 22 patients had their claims settled. RESULTS: Approximately three
      fourths had persistent complaints of jaw pain, jaw dysfunction, and headache, and
      more than 80% reported persistent neck pain. No apparent differences were found
      between those who had and had not settled their insurance claims. CONCLUSION:
      Jaw, head and neck pain, and jaw dysfunction continued to be problems for the
      majority of this patient population, regardless of litigation status in this
      retrospective study.

PMID- 9029466
TI  - The effect of a surface wetting agent on void formation in impressions.
AB  - STATEMENT OF PROBLEM: Impressions free from voids are important for the
      fabrication of accurate restorations. Any material or technique that reduces the
      incidence of bubbles is welcome. PURPOSE: The aim of this study was to determine
      whether the use of a surfactant designed for clinical use (Hydrosystem) reduced
      the number of visible air bubbles on the surface of a range of impression
      materials. MATERIAL AND METHODS: The surfactant was used before impressions were
      recorded with one of the following: a putty-wash condensation silicone, four
      polyvinyl siloxane materials, a polyether, a polysulfide, and an irreversible
      hydrocolloid impression material. Impressions recorded without the use of
      Hydrosystem acted as controls. Impressions were made of two prepared acrylic
      resin teeth in vitro and examined for surface voids by an examiner who was blind
      to whether the surfactant was used. RESULTS: Hydrosystem surfactant significantly
      reduced the number of surface voids when it was used with low-viscosity addition
      cured silicone material but not when used with irreversible hydrocolloid,
      polysulfide, a hydroactive monophase addition-cured silicone, or a putty-wash
      condensation silicone. CONCLUSION: The use of Hydrosystem surfactant may result
      in a clinically significant improvement in impression quality.

PMID- 9029467
TI  - A regression analysis of filler particle content to predict composite wear.
AB  - STATEMENT OF PROBLEM: It has been hypothesized that composite wear is correlated
      to filler particle content. There is a paucity of research to substantiate this
      theory despite numerous projects evaluating the correlation. PURPOSE OF STUDY:
      The purpose of this study was to determine whether a linear relationship existed
      between composite wear and filler particle content of 12 composites. MATERIAL AND
      METHODS: In vivo wear data had been previously collected for the 12 composites
      and served as basis for this study. Scanning electron microscopy and backscatter
      electron imaging were combined with digital imaging analysis to develop "profile
      maps" of the filler particle composition of the composites. These profile maps
      included eight parameters: (1) total number of filler particles/28742.6 microns2,
      (2) percent of area occupied by all of the filler particles, (3) mean filler
      particle size, (4) percent of area occupied by the matrix, (5) percent of area
      occupied by filler particles, r (radius) 1.0 < or = micron, (6) percent of area
      occupied by filler particles, r = 1.0 < or = 4.5 microns, (7) percent of area
      occupied by filler particles, r = 4.5 < or = 10 microns, and (8) percent of area
      occupied by filler particles, r > 10 microns. Forward stepwise regression
      analyses were used with composite wear as the dependent variable and the eight
      parameters as independent variables. RESULTS: The results revealed a linear
      relationship between composite wear and the filler particle content. CONCLUSION:
      A mathematical formula was developed to predict composite wear.

PMID- 9029468
TI  - A comparison of the dimensional accuracy of the splinted and unsplinted
      impression techniques for the Bone-Lock implant system.
AB  - STATEMENT OF PROBLEM: The precise transfer of intraoral relationships of implants
      to laboratory working models is central to the success of implant prostheses.
      PURPOSE: In this study a stone master model incorporating five implants (Bone
      Lock) was used to compare the dimensional accuracy of a splinted impression
      technique with an unsplinted impression technique. METHODS: A three-factor
      analysis of variance was used to examine the effect of technique, relative
      position of the implant on the cast, and plane of measurement. RESULTS: All three
      factors had a significant effect on dimensional accuracy. CONCLUSIONS: The
      splinted technique exhibited more deviation from the master model than the
      unsplinted technique did. This was primarily associated with rotational
      discrepancies around the long axes of the implants for the splinted technique.

PMID- 9029469
TI  - Lipopolysaccharide affinity for titanium implant biomaterials.
AB  - STATEMENT OF PROBLEM: Lipopolysaccharide (LPS) affinity for titanium implant
      biomaterials could affect crevicular LPS concentrations and thereby influence
      periimplant inflammation. PURPOSE OF STUDY: The purpose of this study was to
      evaluate Porphyromonas gingivalis and Escherichia coli LPS affinity for titanium
      biomaterials groups that differed in surface oxide composition and surface
      roughness. MATERIAL AND METHOD: Polished and abraded grade 1 commercially pure
      titanium and grade 5 alloyed extra low interstitial titanium specimens were
      treated with 10 EU/mm2 and radiolabeled LPS. RESULTS: The resultant mean +/- SD
      LPS adherence values ranged from 4.17 +/- 0.29 to 4.79 +/- 0.40 EU/ mm2. No
      difference in adherence and elution was indicated on the basis of LPS type,
      surface oxide composition, or surface roughness. Moreover, P. gingivalis and F.
      coli LPS desorption was below detection. CONCLUSION: Clinically, the high
      affinity of both LPS types for titanium biomaterials may adversely influence the
      periimplant tissue response.

PMID- 9029470
TI  - Check bite impressions using irreversible alginate/reversible hydrocolloid
      combination.
AB  - A restoration that the patient reports as "high" is a common problem for the
      restorative dentist. Check bite, dual bite, or closed mouth impressions address
      this problem effectively by eliminating the opposing arch impression and
      articulating the opposing cast accurately. In this article a procedure that
      combines irreversible hydrocolloid and reversible hydrocolloid results in a
      rapid, clean, and effective solution.

PMID- 9029471
TI  - Support of removable partial dentures in situations with a unilaterally missing
      canine and a curved edentulous ridge.
AB  - The load and movement of abutments and removable partial dentures were examined
      in situations with a unilaterally missing canine and a curved edentulous ridge.
      These measurements were performed on a model adapted to intraoral conditions. In
      this simulation, removable partial dentures supported by incisors may result in
      failure. Spring rest support results in significantly reduced articulation
      vertically and horizontally when compared with solid rest support and avoids
      periodontal overloading.

PMID- 9029472
TI  - Repairing and strengthening a fractured Hader bar.
AB  - Stresses from occlusion and metal fatigue over time can cause fracture of
      overdenture retention bars. Often failure of the bar necessitates the removal and
      remake of the bar. This may damage the abutment, especially if there are dowel
      posts involved. This article describes a method for reinforcing the existing bar
      without having to remove the bar or significantly alter the overdenture. The
      fractured bar can be prepared in the mouth to receive a reinforcing
      superstructure that will be cemented.

PMID- 9029473
TI  - Hypersensitivity to methyl methacrylate: mode of treatment.
AB  - This article describes the treatment of a patient who experienced a delayed
      hypersensitivity reaction associated with acrylic resin. Patch testing revealed
      an allergy to methyl methacrylate monomer. Patients with a known or suspected
      allergy of this type should be treated by alternative methods. Dental procedures
      in which negligible contact of the oral mucosa with methyl methacrylate are
      presented.

PMID- 9029474
TI  - Denture duplication technique with alternative materials.
AB  - This denture duplication technique uses addition silicone impression material. It
      is an easy, time-efficient method that allows the fabrication of the duplicate
      denture at a convenient time.

PMID- 9029475
TI  - Multiple prosthodontic uses for permanent crown remover forceps.
AB  - Practitioners will find multiple uses for Perm Gripper forceps. These crown
      remover forceps are likely to become an indispensable adjunct in the busy
      prosthodontic practice.

PMID- 9029476
TI  - Bite fork modification.

PMID- 9029477
TI  - Modification of the centric lock assembly of a semiadjustable articulator.

PMID- 9029478
TI  - Genetic approaches to CNS disorders with particular reference to GABAA-receptor
      mutations.
AB  - The tools of molecular biology will bring the field of human genetics into a new
      era by permitting the analysis of the genetic contribution to disease. Most
      single gene disorders, inherited in a Mendelian fashion, will be molecularly
      diagnosed. In addition, the genetic susceptibility of common, complex diseases
      such a schizophrenia can be clarified, even though the conditions are not
      inherited as Mendelian characteristics. The mapping of the human genome will
      increase the rate at which new disease genes are identified and isolated.
      Finally, the development of genetically engineered animal models will help to
      dissect the steps involved in physiological and pathophysiological processes and
      thereby enhance our understanding of complex biological systems.

PMID- 9029479
TI  - Allosteric modulation of Torpedo nicotinic acetylcholine receptor ion channel
      activity by noncompetitive agonists.
AB  - Similar to other neuroreceptors of the vertebrate central nervous system, the
      nicotinic acetylcholine receptor (nAChR) is subject to modulatory control by
      allosterically acting ligands. Of particular interest in this regard are
      allosteric ligands that enhance the sensitivity of the receptor to its natural
      agonist acetylcholine (ACh), as such ligands could be useful as drugs in diseases
      associated with impaired nicotinic neurotransmission. Here we discuss the action
      of a novel class of nAChR ligands which act as allosterically potentiating
      ligands (APL) on the nicotinic responses induced by ACh and competitive agonists.
      In addition, APLs also act as noncompetitive agonists of very low efficacy, and
      as direct blockers of ACh-activated channels. These actions are observed with
      nAChRs from brain, muscle and electric tissue, and they depend on the structure
      of the APL and the concentration range applied. We focus here on Torpedo nAChR
      because (i) the unusual pharmacology of these ligands was first discovered with
      this system, and (ii) large quantities of this receptor are readily available for
      biochemical studies.

PMID- 9029480
TI  - In vitro translation analysis of integral membrane proteins.
AB  - A method of in vitro translation scanning was applied to a variety of polytopic
      integral membrane proteins, a transition metal P type ATPase from Helicobacter
      pylori, the SERCA 2 ATPase, the gastric H+,K+ ATPase, the CCK-A receptor and the
      human ileal bile acid transporter. This method used vectors containing the N
      terminal region of the gastric H+,K+ ATPase or the N terminal region of the CCK-A
      receptor, coupled via a linker region to the last 177 amino acids of the beta
      subunit of the gastric H+,K+ ATPase. The latter contains 5 potential N-linked
      glycosylation sites. Translation of vectors containing the cDNA encoding one, two
      or more putative transmembrane domains in the absence or presence of microsomes
      allowed determination of signal anchor or stop transfer properties of the
      putative transmembrane domains by the molecular weight shift on SDS PAGE. The P
      type ATPase from Helicobacter pylori showed the presence of 8 transmembrane
      segments with this method. The SERCA 2 Ca2+ ATPase with this method had 9
      transmembrane co-translational insertion domains and coupled with other evidence
      these data resulted in a 11 transmembrane segment model. Translation of segments
      of the gastric H+,K+ ATPase provided evidence for only 7 transmembrane segments
      but coupled with other data established a 10 membrane segment model. The G7
      protein, the CCK-A receptor showed the presence of 6 of the 7 transmembrane
      segments postulated for this protein. Translation of segments of the human ileal
      bile acid transporter showed the presence of 8 membrane insertion domains.
      However, translation of the intact protein provided evidence for an odd number of
      transmembrane segments, resulting in a tentative model containing 7 or 9
      transmembrane segments. Neither G7 type protein appeared to have an arrangement
      of sequential topogenic signals consistent with the final assembled protein. This
      method provides a useful addition to methods of determining membrane domains of
      integral membrane proteins but must in general be utilized with other methods to
      establish the number of transmembrane alpha-helices.

PMID- 9029481
TI  - Constitutively active G protein-coupled receptors: potential mechanisms of
      receptor activation.
AB  - Mutations of G protein-coupled receptors can increase their constitutive (agonist
      independent) activity. Some of these mutations have been artificially introduced
      by site-directed mutagenesis, others occur spontaneously in human diseases. The
      analysis of the constitutively active G protein-coupled receptors has provided
      important informations about the molecular mechanisms underlying receptor
      activation and drug action.

PMID- 9029482
TI  - Interactions of alpha-melanotropin and agouti on B16 melanoma cells: evidence for
      inverse agonism of agouti.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH, alpha-melanotropin) and agouti
      control the switch between eumelanin and pheomelanin synthesis in mammalian
      melanocytes. Here we investigated interactions between alpha-MSH, agouti protein,
      cAMP elevating agents and phorbol ester on mouse B16 melanoma cells. Agouti (Kd
      3.7 nmol/l) and alpha-MSH (Kd 2.3 nmol/l) had similar affinities to the MC1
      melanocortin receptor. Both alpha-MSH and agouti induced MC1 receptor down
      regulation. Agouti antagonized melanogenesis induced by alpha-MSH, forskolin,
      cholera toxin (CT), and pertussis toxin (PT). It also reduced the constitutive
      melanin formation of long-term cultures. Cell proliferation was inhibited by
      agouti (43% at 100 nM). This effect was reversed by alpha-MSH, forskolin, or CT.
      B16-G4F cells, a cell variant that lacks the MC1 receptor, did not respond to
      agouti. From these results we conclude that agouti shows the characteristics of
      an inverse agonist acting through the MC1 receptor.

PMID- 9029483
TI  - Development of stable cell lines expressing different subtypes of GABAA
      receptors.
AB  - The experiments reported here were motivated by our interest to express in stably
      transfected cells large amounts of recombinant rat GABAA receptors. For this, we
      developed an original two step selection strategy, in which the first step
      consisted of transfecting HEK 293 cells with rat GABAA receptor alpha and beta
      subunits. G 418 resistant colonies isolated at this step were screened for [3H]
      muscimol binding to select for those that coexpressed alpha- and beta-subunits.
      The best alpha and beta subunit expressing colony was then supertransfected with
      a plasmid coding for the gamma rat GABAA receptor subunit and a mutant DHFR gene.
      After a second round of selection, this time in presence of methotrexate, those
      colonies that coexpressed ternary alpha beta gamma GABAA receptor combinations
      were distinguished using [3H] flumazenil as a probe. This strategy was applied to
      the isolation of 3 GABAA receptor clones, alpha 1 beta 2 gamma 2s, alpha 3 beta 2
      gamma 2s and alpha 5 beta 3 gamma 2s, that expressed relatively high levels of
      these proteins. These 3 cell lines exhibited pharmacological and functional
      properties similar to cells transiently-transfected with equivalent subunit
      combinations. These cell lines therefore provide attractive models with which to
      evaluate the intrinsic activity and potency of compounds at recombinant GABAA
      receptor subtypes.

PMID- 9029485
TI  - Signal perception and intracellular signal transduction in plant pathogen
      defense.
AB  - Disease resistance in plant/pathogen interactions requires sensitive and specific
      recognition mechanisms for pathogen-derived signals in plants. Cultured parsley
      (Petroselinum crispum) cells respond to treatment with a crude cell wall
      preparation derived from the phytopathogenic fungus Phytophthora sojae with
      transcriptional activation of the same set of defense-related genes as are
      activated in parsley leaves upon infection with fungal spores. A 13 amino acid
      core sequence (Pep-13) of a 42 kDa fungal cell wall glycoprotein was identified,
      which stimulates the same responses as the crude cell wall elicitor, namely
      macroscopic Ca2+ and H(+)-influxes, effluxes of K(+)- and Cl- ions, production of
      active oxygen species (oxidative burst), defense-related gene activation, and
      formation of antifungal phytoalexins. Using [125I]Tyr-Pep-13 as ligand in binding
      assays, a single-class high-affinity binding site in parsley microsomal membranes
      and protoplasts could be detected. Binding was specific, saturable, and
      reversible. By chemical crosslinking, a 91 kDa parsley plasma membrane protein
      was identified to be the receptor of the peptide elicitor. Isolation of this
      receptor protein involved in pathogen defense in plants is under way.

PMID- 9029484
TI  - Expression of ligand-gated ion channels with the Semliki Forest virus expression
      system.
AB  - Two types of ligand-gated ion channels were expressed with the Semliki Forest
      virus (SFV) expression system. The cDNAs for mouse serotonin 5-HT3 receptor and
      rat and human purinoreceptor P2x subtypes were introduced into the pSFV1 vector.
      In vitro transcribed RNAs were coelectroporated with pSFV-Helper2 RNA into BHK
      cells, where in vivo packaging resulted in high titer SFV-5-HT3 and SFV-P2x virus
      stocks. Infection of BHK, CHO and RIN cells resulted in high-level expression of
      recombinant receptors. Saturation binding analysis indicated the presence of more
      than 3 x 10(6) 5-HT3 receptors per cell. Binding studies on isolated membranes
      yielded from 10 to 60 pmol of either 5-HT3 or P2x receptor per mg protein.
      Functional responses to the P2x receptors were demonstrated in SFV-infected CHO
      cells by Ca2+ mobilization or by 45Ca2+ influx. High amplitude
      electrophysiological responses were also detected for both SFV-5-HT3 and SFV-P2x
      infected CHO cells in whole-cell patch clamp recordings. To facilitate the
      purification procedure of SFV-expressed recombinant receptors a histidine tag was
      introduced at the C-terminus of the 5-HT3 receptor. This 5-HT3His receptor showed
      high levels of expression, specific binding and high amplitude
      electrophysiological responses. For large scale expression the BHK cells were
      adapted to suspension culture and were efficiently infected in a 11.5 liter
      fermentor culture with SFV-5-HT3His resulting in high-level expression, 52 pmol
      receptor per mg protein corresponding to 3.2 x 10(6) receptors per cell.

PMID- 9029486
TI  - Specific modulation of two neuronal digitalis receptors by anaesthesia.
AB  - Three isoenzymes of digitalis receptors (alpha 1, alpha 2, alpha 3) in the brain
      and only one in the kidney (alpha 1) can be distinguished by their ouabain
      affinities and their responsiveness to sodium. Since we have reported modulations
      for these digitalis receptors by their fatty acid membrane environment,
      anaesthesics could bind on and modulate either directly these receptors or
      indirectly by disturbing membrane lipids. The aim of this study was to evaluate
      this anaesthetic action on apparent ouabain affinities and sodium dependence of
      cerebral and renal Na+, K(+)-ATPase isoenzymes activities. Rat brain and kidney
      membrane fractions with pentobarbital-induced anaesthetized state were compared
      to an unanaesthetized state for their (1) fatty acid composition of total
      membrane phospholipids, (2) responsiveness to ouabain and (3) Na+ dependence of
      digitalis receptors. An anaesthesia period of 10 minutes induced (1) a fatty acid
      modification of brain membranes and (2) a significant sensibilization to ouabain
      for the alpha 2 and alpha 3 isoforms of digitalis receptors (alpha 2, IC50; 8.2
      +/- 0.5 x 10(-7) mol/l vs 4.5 +/- 0.2 x 10(-7) mol/l; alpha 3, IC50; 6.0 +/- 0.3
      x 10(-8) mol/l vs 2.5 +/- 0.1 x 10(-8). In contrast, the ouabain affinity of the
      alpha 1 subunit expressed in kidney and brain membranes was unaltered. No
      anaesthetic effect was observed on the Na+ dependence of the alpha 1 isoenzyme in
      the brain (4 mmol/l) and the kidney (8 mmol/l). Pentobarbital induced a
      desensibilization for alpha 2-receptors (8.3 +/- 0.5 vs 16.0 +/- 1.4 mmol/l Na+)
      and a sensibilization for alpha 3-receptors (14.4 +/- 0.8 vs 10 +/- 1.3 mmol/l
      Na+). These altered properties could be related to a selective modification of
      the fatty acid composition and/or to the presence of a specific binding site for
      pentobarbital on these two neuronal digitalis receptors.

PMID- 9029487
TI  - Cyclosporin A potentiates receptor-activated [Ca2+]c increase.
AB  - The use of the immunosuppressant cyclosporin A (CsA) is frequently associated
      with hypertension. Drug-induced local vasoconstriction appears to be responsible
      for this effect. Using fura-2 and 45Ca2+ efflux techniques, we have examined
      variations in the cytosolic calcium concentration ([Ca2+]c) in rat aortic smooth
      muscle cells and have shown that increases in [Ca2+]c after [Arg8]vasopressin,
      serotonin, endothelin-1 or angiotensin II stimulation were potentiated after
      preincubation of cells with CsA. This effect was independent of cyclophilin or
      calcineurin inhibition by CsA. Measurements of inositol phosphates (InsPn) after
      agonist stimulation showed that CsA also potentiated their formation. As for
      45Ca2+ efflux this effect was not related to cyclophilin or calcineurin
      inhibition. Direct stimulation of G proteins with aluminium tetrafluoride induced
      an increase in InsPn formation and 45Ca2+ efflux. Neither of these responses was
      potentiated by CsA. These results indicate that CsA acts on a target upstream of
      G protein activation, possibly at the receptor level, resulting in a potentiation
      of InsPn formation and subsequent calcium increase.

PMID- 9029488
TI  - Studies on capacitative calcium entry in vascular smooth muscle cells by
      measuring 45CA2+ influx.
AB  - Capacitative calcium entry was studied in the A7r5 vascular smooth muscle cell
      line by measuring 45Ca2+ influx. Entry was induced by depletion of the Ca2+ pools
      by either the receptor agonist [Arg]8 vasopressin (AVP) or the SR-Ca(2+)-ATPase
      inhibitor thapsigargin (TG). TG showed a higher efficacy for calcium influx than
      AVP. This is probably due to a larger Ca2+ release from the pools induced by TG
      compared to AVP and the irreversible inhibition of the SR-Ca(2+)-ATPase by TG
      causing influx to persist for a longer period of time. At maximally effective
      concentrations signals induced by AVP and TG were synergistic in the absence but
      not in the presence of the intracellular calcium chelator, 1,2-bis(2
      aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA). Depolarisation with 55
      mM KCl completely inhibited 45Ca2+ influx induced by TG but only slightly the one
      induced by AVP, both effects being less pronounced in the presence of BAPTA.
      [Ca2+]c signals induced by AVP and TG were both inhibited by depolarisation. In
      conclusion, although our results show differences between AVP- and TG- induced
      Ca2+ influx, they can be explained by their different mechanism of action and are
      in accordance with an activation of the same capacitative entry pathway by both
      agents.

PMID- 9029489
TI  - Characterisation of [3H]-darifenacin as a novel radioligand for the study of
      muscarinic M3 receptors.
AB  - Darifenacin, (S)-2-[1-[2,3-dihydrobenzofuran-5-yl]-3- pyrrolidinyl]-2,2
      diphenylacetamide, is a novel muscarinic M3 antagonist. In this study we have
      compared the binding of [3H]-darifenacin to the five cloned human muscarinic
      receptors (m1-m5) expressed in CHO cells. [3H]-darifenacin binds with 6 fold
      higher affinity to m3 (KD = 0.33 nmol/l) over m1 (KD = 1.6 nmol/l) receptors.
      There was no specific binding of [3H]-darifenacin to m2 receptors and specific
      binding to m4 and m5 receptors was insufficient to determine a KD. Binding of
      [3H]-darifenacin to m1 and m3 was displaced by atropine (m1 pKi = 9.36, m3 pKi =
      9.4), 4-DAMP (m1 pKi = 9.04, m3 pKi = 9.19), pirenzepine (m1 pKi = 8.63, m3 pKi =
      6.85), methoctramine (m1 pKi = 7.28, m3 pKi = 6.63), and darifenacin (m1 pKi =
      8.36, m3 pKi = 9.14), demonstrating that [3H]-darifenacin represents the first
      selective m3 radioligand.

PMID- 9029490
TI  - Characterization of a ryanodine receptor in Periplaneta americana.
AB  - Specific binding sites for the alkaloid ryanodine were characterized in membrane
      preparations from sarcoplasmatic reticulum of Periplaneta americana skeletal
      muscle. Binding of [3H]ryanodine was optimal at pH 8 and at CaCl2 concentration
      of about 300 mumol l-1. The Ca-chelating agents EGTA (100 mumol l-1) and EDTA
      (100 mumol l-1) abolished 95% and 90% of the [3H]ryanodine binding respectively.
      Preincubation with Ca2+ (100 mumol l-1) restored the ryanodine binding in
      presence of up to 300 mumol l-1 EGTA. Radioligand binding experiments showed one
      class of high affinity binding sites for ryanodine. Determination of rate
      constants revealed 7.05 x 10(6) l mol-1 min-1 for associating and 3.77 x 10(-3)
      min-1 for the dissociating [3H]ryanodine ryanodine receptor complex. Solubility
      of the ryanodine receptor was examined with different anionic, non-ionic and
      zwitterionic detergents. Best solubilization results of "calcium release channel"
      of cockroach muscle membrane preparations were obtained with the detergent CHAPS
      in a concentration of 5 mg ml-1.

PMID- 9029491
TI  - MSH receptors and the response of human A375 melanoma cells to interleukin-1
      beta.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH, alpha-melanotropin) has been
      shown to be an inhibitory factor in many immunologic and inflammatory processes
      involving the cytokine interleukin-1 (IL-1). As the mechanism of the interaction
      between IL-1 and alpha-MSH at the receptor level is unknown, we have studied the
      role of MC1 melanocortin receptors in two variants of the human melanoma cell
      line A375 differing in their sensitivity to the cytostatic effects of IL-1 beta.
      Both IL-1 sensitive (A375r-) and resistant cells (A375r+) carry specific high
      affinity receptors for IL-1, albeit their concentration is 10-fold higher in
      A375r+ cells. In A375r- cells, MC1 receptors are absent or below the level for
      reliable detection in the binding assay. Conversion of A375r- to A375r+ cells by
      prolonged culture in medium not depleted of endotoxin led to the appearance of
      MC1 receptors (KD 0.4 +/- 0.123 nmol/l; 608 +/- 134 receptors/cell). Stable
      transfection of A375r- cells with the human MC1 receptor did not, however, render
      them resistant to the cytostatic effect of IL-1 beta on concomitant treatment
      with alpha-MSH or result in the production of IL-6 on treatment with IL-1 beta.
      Therefore, the presence of MC1 receptors on the surface of A375 cells or their
      binding to alpha-MSH does not seem to be a factor in cytokine resistance or IL-6
      secretion. No interaction between IL-1 beta and alpha-MSH could be demonstrated
      at the cellular level in this melanoma cell line.

PMID- 9029492
TI  - IL-1 beta transduces different signals than IL-1 alpha leading to class II
      antigen expression on beta-insulinoma RIN-5AH cells through specific receptors.
AB  - Like most cytokines, IL-1 transduces its signals for growth, differentiation and
      diverse cellular functions after binding to specific receptors on the cell
      surface. Up to now two IL-1 receptors have been reported, type I which induces
      signal transduction and type II which binds IL-1 but does not transduce
      signalling. By using the rat insulinoma RIN-5AH cell line that expresses both
      types of receptor mRNA, and computer-assisted binding analysis, we show that
      interleukin-1 beta (IL-1 beta) binds to a single class of high affinity receptors
      with a Kd of 155 pmol/l. The average number of receptors on adherent cell layer
      is calculated to be 7300 per cell. 125I-IL-1 beta binding can be competed out by
      unlabelled IL-1 beta. 125I-IL-1 alpha binding can be also obtained and is subject
      to competition by cold IL-1 alpha. Its saturation curve, however, varies within
      experiments due to differential receptor up-regulation. These results have also
      been confirmed by FACS analysis using specific antibodies to type I and II IL-1
      receptors, where type I receptor antibody binds strongly to RIN-5AH cells, and
      type II receptor antibody shows weak staining, also due to inadequate receptor up
      regulation. In order to determine whether functional signal transduction occurs
      via the receptors detected, it is shown that IL-1 beta is able to induce MHC
      class II antigen expression on the surface of the RIN cells, whereas IL-1 alpha
      is unable to do so, indicating different signal reception by the cells. IL-1 beta
      induced class II upregulation shows moderate signs of p21ras or/and PKC
      dependency, whereas IL-1 alpha strongly activates both pathways that probably
      regulate different functions. Finally, both IL-1 alpha and beta induce nitric
      oxide (NO) production in a time-dependent fashion which appears to be unrelated
      to the signals and pathways described, but may be involved in the onset of
      autoimmune type 1 diabetes.

PMID- 9029493
TI  - Electrophysiology: a method to investigate the functional properties of ligand
      gated channels.
AB  - Ligand-gated channels (LGCs) play a fundamental role in the fast transmission of
      electrical activity from neuron to neuron and/or to effector cells. Studies of
      LGCs in isolation have become possible since the identification of genes coding
      for these membrane proteins together with the establishment of reconstitution
      techniques in host systems. Methods for electrophysiological investigations of
      LGCs reconstituted either in the Xenopus oocytes or stably tranfected in cell
      lines are discussed. Functional studies of reconstituted receptors enable fast
      determination of LGCs' pharmacological profiles and comparison of their
      physiological properties. Combination of molecular engineering with physiological
      measurements allows studies with unpreceeding resolution and it is now possible
      to examine at the amino-acid level the contribution of some residues in the
      formation of the ligand-binding site or the ionic channel domains.

PMID- 9029494
TI  - Nicotinic acetylcholine receptors on hippocampal neurons: distribution on the
      neuronal surface and modulation of receptor activity.
AB  - The recent development of a technique that uses infrared microscopy for the
      visualization of well-defined areas on the surface of neurons, and a computerized
      system of micromanipulators led to the discovery that functional nicotinic
      acetylcholine receptors (nAChRs) are expressed at higher density on the dendrites
      than on the soma of rat hippocampal neurons. The finding that the expression of
      alpha-bungarotoxin-sensitive, alpha 7-bearing, nAChRs and dihydro-beta
      erythroidine-sensitive, alpha 4 beta 2 nAChRs tends to increase along the
      dendritic length suggests that these receptors may be highly involved in the
      integration of synaptic functions in hippocampal neurons. The present report also
      discusses the finding that ligands such as the anticholinesterase galanthamine
      can modulate the nAChR activity by binding to a novel receptor site, and that 5
      hydroxytryptamine (5-HT) may serve as an endogenous ligand for this site. The
      ability of 5-HT to modulate the nAChR function in vivo supports the concept that
      the overall CNS function is determined not only by the neuronal network
      established by the neuronal wiring, but also by a chemical network established by
      the ability of a single substance to act as the primary neurotransmitter in one
      system and as a co-transmitter in another system.

PMID- 9029495
TI  - Full and partial agonists induce distinct desensitized states of the 5-HT3
      receptor.
AB  - 5-HT3 receptor-mediated ion currents evoked by the full agonists 5-hydroxy
      tryptamine (5-HT), quaternary 5-HT (5-HTQ), meta-chlorophenylbiguanide (mCPBG)
      and the partial agonists dopamine and tryptamine have been investigated in whole
      cell voltage clamp experiments on N1E-115 mouse neuroblastoma cells. All agonists
      desensitize the 5-HT3 receptor completely with a steep concentration dependence
      and a potency order of: mCPBG > 5-HTQ approximately 5-HT > > tryptamine >
      dopamine. The time course of recovery from desensitization depends on the agonist
      used. Recovery from partial agonist-induced desensitization is single
      exponential, whereas the desensitization induced by full agonists recovers with
      sigmoid kinetics, suggesting at least 3 transitions between 4 states. It is
      concluded that full and partial agonists induce distinct desensitized states.

PMID- 9029496
TI  - Genetic manipulations of cholinergic communication reveal trans-acting control
      mechanisms over acetylcholine receptors.
AB  - Several approaches have been developed for genetic modulations of receptor
      expression. These initiated with gene cloning and heterologous expression in
      microinjected Xenopus oocytes, and proceeded through transgenic expression and
      genomic disruption of receptor genes in mice. In addition, antisense treatments
      have reduced receptor levels in a transient, reversible manner. Integration of
      foreign DNA with host genomic sequences yields both cis- and trans-acting
      responses. These may depend on the DNA integration site, host cells condition and
      most importantly, the affected signal transduction circuit. For example,
      acetylcholinesterase (AChE) overexpression in microinjected Xenopus tadpoles has
      been shown to upregulate alpha-bungarotoxin binding levels, indicating trans
      acting control conferring overproduction of muscle nicotinic acetylcholine
      receptors. In transgenic mice expressing human AChE, the hypothermic response to
      oxotremorine was suppressed, reflecting modified levels of brain muscarinic
      receptors. To dissociate the feedback processes occurring in transfected cells
      from responses related to DNA integration, we examined the endogenous expression
      of the alpha 7 neuronal nicotinic acetylcholine receptor in PC12 cells
      transfected with DNA vectors carrying alternative splicing variants of human AChE
      mRNA. Our findings demonstrate suppression of alpha 7 receptor levels associated
      with the accumulation of foreign DNA in the transfected cells. Acetylcholine
      receptor levels thus depend on multiple elements, each of which should be
      considered when genetic interventions are employed.

PMID- 9029498
TI  - Expression of functional human muscarinic M2 receptors in different insect cell
      lines.
AB  - Human M2 receptors were expressed using the baculovirus expression system in
      three different insect cell lines: Sf9, Sf21 and High5. The level of expression
      was slightly increased in Sf21 cells versus Sf9 cells. In contrast, High5 cells
      were not able to produce more recombinant protein than Sf9. We also show that in
      both Spodoptera frugiperda cell lines a peak of expression was reached after 6
      days of infection, whereas in High5 cells, the maximum of expression occurred
      after 3 days. Immunodetection of m2 muscarinic receptor clearly shows that the
      expressed protein undergoes significant proteolysis in both the Sf9 and High5
      cells, whereas in the Sf21 cells this phenomenon was less detectable.
      Additionally, we show that in all three cell lines, the expressed recombinant
      receptor was functional in that it was able to stimulate GTP gamma S binding in
      the presence of exogenous G-proteins. Analysis of the population of G-proteins (G
      alpha i, G alpha o and G beta common) in Sf21 and High5 cells is provided.

PMID- 9029499
TI  - Regulation of gene expression by nuclear hormone receptors.
AB  - Steroids and thyroid hormones, as well as vitamin D, retinoids and some nutrient
      metabolites (fatty acids, prostaglandins, farnesol metabolites) act by binding to
      members of the zinc-finger containing superfamily of nuclear hormone receptors.
      These receptor proteins bind directly to specific DNA recognition sequences
      (hormone response elements) in the promoter region of target genes, resulting in
      the alteration of the transcription initiation rate. While the principle of
      action of these receptors appears to be quite simple, the promiscuous behavior of
      some members of this family as well as cross-talk with other signaling systems
      result in an intricate regulatory network with distinct particularities for each
      receptor type. Specific areas of current interest in nuclear receptor research
      are: (i) the mechanisms for target gene specificity, which occur at the level of
      receptor expression, ligand metabolism and/or DNA sequence; (ii) cross-talk with
      other signaling systems resulting in the modulation of the transcriptional
      activity of the ligand-activated receptor through phosphorylation and/or
      heterodimerization with shared nuclear factors; and (iii) the discovery of novel
      agonistic and antagonistic ligands for established and orphan nuclear receptors.
      Recent insights through screening strategies for putative ligands, the cloning of
      co-activator proteins, as well as the characterization of human and animal models
      with germline and somatic mutations in nuclear receptors have resulted in
      important insights into some of the above questions, which are fundamental for a
      better understanding of the role of these hormone-activated transcription factors
      during development and cell differentiation.

PMID- 9029497
TI  - Investigation of growth hormone releasing hormone receptor structure and activity
      using yeast expression technologies.
AB  - Growth hormone releasing hormone (GHRH) is the positive regulator of growth
      hormone synthesis and secretion in the anterior pituitary. The peptide confers
      activity by binding to a seven transmembrane domain G protein-coupled receptor.
      Signal transduction proceeds through subsequent G alpha s stimulation of adenylyl
      cyclase. To investigate ligand/receptor and receptor/G protein associations, the
      human GHRH receptor was expressed in a modified S. cerevisiae strain which allows
      for facile measurement of receptor activity by cell prototrophy mediated by a
      reporter gene coupled to the yeast pheromone response pathway. GHRH-dependent
      signal activation in this system required the substitution of yeast G alpha
      protein with proteins containing C-terminal regions of G alpha s. A D60G variant
      (analogous to the little mouse mutation) of the receptor failed to respond to
      agonist. In parallel studies, GHRH29 and the N-terminal extracellular region of
      the receptor were expressed as Gal4 fusion proteins in a 2-hybrid assay. A
      specific interaction between these proteins was readily observed. The D60G
      mutation was engineered into the receptor fusion protein. This protein failed to
      interact with the ligand fusion, confirming the specificity of the association
      between unmodified proteins. These two yeast expression technologies should prove
      invaluable in additional structure/activity analyses of this ligand/receptor pair
      as well as other peptide ligands and receptors.

PMID- 9029500
TI  - Steroid receptors in the rat hippocampus: a note to the methodology of their
      binding assay.
AB  - Mineralocorticoid (MR) and glucocorticoid (GR) receptors in the rat hippocampus
      are linked to several cognitive functions of the animal and seem to play an
      important role in the response to various stressors. Their assessment by binding
      experiments brings about problems associated with their intracellular
      compartmentalization, and in particular with the separation of the bound and free
      ligands. Adrenalectomy 24 h before sacrificing is commonly used to clear the
      circulating adrenal steroids, and to facilitate their dissociation from
      hippocampal MR and GR. We have successful attempted to use dialysis to these
      purposes and thus, to avoid a potential surgical stress. Without dialysis, only
      GR can be measured in the cytosol from intact rats, while the corresponding
      pellet contains MR as a component of the cell nuclei. The bound ligand fraction
      was separated by filtration on polyethyleneimine pretreated glass fiber filters
      as suggested earlier. The method has clear-cut preferences compared to any
      alternative used up to now. Discrimination between the two receptor types can be
      optimally achieved in a cross-displacement experiment in which two labeled
      ligands possessing various affinities to individual receptors (in our case:
      corticosterone and aldosterone, or their synthetic analogs) are displaced with
      the two corresponding nonlabelled ligands from their receptors. Computations can
      be carried out with LIGAND software which yield accurate values of binding
      parameters.

PMID- 9029501
TI  - Application of a novel method for the comparison of DNA binding parameters of the
      two human thyroid hormone receptor subtypes hTR alpha 1 and hTR beta 1.
AB  - DNA-binding characteristics of the two human thyroid hormone receptors alpha 1
      and beta 1 (hTR alpha 1 and hTR beta 1) were studied by applying the recently
      developed solid-phase scintillation technique. Biotinylated double stranded
      oligonucleotides containing thyroid hormone response elements (TRE) were
      immobilized to streptavidin coated scintillating microtiter plates. The TRE:s
      consisted of variants of the consensus core sequence AGGTCA as monomers or as
      dimers in direct repeats. Equilibrium binding of radioactive labelled hTR alpha 1
      and hTR beta 1 were studied. Metabolically 35S-labelled hTR (in vitro translated
      cDNA) as well as hTR expressed in the baculovirus-system and labelled with 125I
      triiodothyronine (125I-T3) were used. In binding saturation experiments, the
      affinity for the TRE:s investigated did not differ greatly between hTR alpha 1
      and hTR beta 1. No significant effects of T3 on the amplitude of DNA binding of
      either hTR alpha 1 or hTR beta 1 to the single site response elements could be
      demonstrated. Receptor binding to direct repeats was stimulated by the hormone in
      the case of the hTR beta 1. The hTR alpha 1 binding to direct repeats was not
      significantly altered by T3. The single site octameric variant of a TRE,
      TAAGGTCA, was observed to bind tighter to the hTR:s as compared to the hexameric
      variant AGGTCA. In the binding competition format, with one response element
      immobilized and other (un-biotinylated) added to the reaction mixture, there was
      a larger dynamic range for the affinity constants (IC50) as compared to the
      affinity constants (Kd) obtained in the binding saturation experiments. The
      present quantitative results confirm previous reports obtained with qualitative
      methods like gel shift assays. The method described here is applicable in basic
      research concerning characterisation of DNA binding of nuclear receptors. It also
      lends itself to automatization in high capacity formats.

PMID- 9029502
TI  - Differential targeting and retention of G protein-coupled receptors in polarized
      epithelial cells.
AB  - Localization of receptors in discrete cellular microdomains undoubtedly
      contributes to their interaction with particular effectors and receptor targets.
      For G protein-coupled receptors, virtually nothing is known about the mechanisms
      and structural features responsible for their targeting to and retention in
      varying surface domains. We have shown that the Gi/ Go-coupled alpha 2A
      adrenergic receptor (alpha 2AAR) is directly targeted to the lateral subdomain of
      MDCK II cells. Mutational analysis has revealed that regions in or near the
      bilayer are likely critical for alpha 2AAR targeting, whereas endofacial domains
      contribute to alpha 2AAR retention on the lateral surface. Although the alpha
      2BAR also is enriched on the lateral subdomain at steady-state, its polarization
      occurs after initial random delivery to both apical and basolateral surfaces
      followed by a selective accumulation on the lateral subdomain. The alpha 2CAR
      also is expressed on the lateral subdomain and achieves its localization via
      direct delivery to the basolateral surface; however, the alpha 2CAR also exists
      in an as yet not fully characterized intracellular compartment. Interestingly,
      another Gi/Go-coupled receptor, the A1 adenosine receptor, is enriched on the
      apical surface of MDCK II calls and achieves this localization by direct apical
      delivery. These findings indicate that receptor delivery to polarized surfaces is
      not determined by receptor coupling to a specific subpopulation of G proteins.

PMID- 9029503
TI  - The elusive nature of cerebellar somatostatin receptors: studies in rat, monkey
      and human cerebellum.
AB  - The pharmacological profile and localization of somatostatin (SRIF) receptors
      were determined in rat, monkey and human cerebellum. In rat cerebellar cortex,
      low sst1/sst4, intermediate sst2 and very high sst3 receptor mRNA levels were
      found. sst1 mRNA was also expressed in the deep cerebellar nuclei. [125I]Tyr3
      octreotide binding sites in cerebellar membranes correlated with recombinant
      sst2, but not with sst5 or sst3 receptors and were found in the molecular layer
      of the cerebellum. [125I]CGP 23996 (in Na(+)-buffer) binding in rat cerebellum
      correlated with sst1 or sst4, but not with sst2, sst3 or sst5 receptor binding.
      Similar data were obtained in rhesus monkey cerebellum. mRNAs for all five
      receptors were found in the granule cell layer of the human cerebellum and/or in
      the dentate nucleus. [125I]Tyr3-octreotide binding was strong in the molecular
      layer and correlated with that of recombinant sst2 receptors, but not with sst3
      or sst5 receptors. [125I]CGP 23996 (in Mg(++)-buffer) binding was heterogeneous
      (about 75%, to sst2 and 25% to sst1 and/or sst4 receptors). The molecular and
      granular layers were equally and the dentate nucleus strongly labeled. Thus, SRIF
      receptors of the sst2, sst1 and/or sst4 subtype are presnt in the rat, monkey and
      human cerebellum. In the latter two species, the sst2 type appears to be
      predominant. Surprisingly, the high expression of sst3 receptor mRNA is not
      supported by radioligand binding data in any of the species studied. The reason
      for this discrepancy remains to be elucidated.

PMID- 9029504
TI  - Fluorescent labelled analogues of neuropeptide Y for the characterization of
      cells expressing NPY receptor subtypes.
AB  - Porcine neuropeptide Y (NPY), a 36 amino acid hormone of the pancreatic
      polypeptide family, and subtype selective analogues have been synthesized by
      solid phase peptide synthesis. The peptides were labelled with Cy3, a
      commercially available fluorescent marker based on a cyanine dye, by solid phase
      strategy. During the cleavage a partial fragmentation of the fluorescent marker
      occurred. This has been investigated by means of HPLC and electrospray mass
      spectrometry. The labelled analogues of NPY showed high affinity to the NPY
      receptor subtypes Y1 and Y2. Thus, Cy3-NPY, Y1-selective Cy3-[Pro34] NPY and Y2
      selective Cy3-[Ahx5-24] NPY were used to label SK-N-MC- and SMS-KAN-cells, which
      are stably expressing the Y1-(SK-N-MC) and the Y2-receptor subtype (SMS-KAN). The
      binding of the labelled analogues to the receptors was reversible and specific.
      The photoactivatable analogue, [(Tmd)Phe27] NPY, which showed high affinity to
      both receptor subtypes was labelled with Cy3 in solution. Whereas the fluorescent
      labelling of the cells with analogues without photoactivatable amino acid was
      reversible, successful photocrosslinking could be investigated by the
      irreversible staining of the cells using Cy3-[(Tmd)Phe27] NPY. These subtype
      selective analogues are exciting tools to trace receptors in tissues and to
      identify the pharmacologically characterized subtypes without radioactivity.

PMID- 9029505
TI  - Distinct binding patterns of [3H]raclopride and [3H]spiperone at dopamine D2
      receptors in vivo in rat brain. Implications for pet studies.
AB  - Positron emission tomography studies (PET) on dopamine (DA) D2 receptors of
      schizophrenics provided conflicting data, perhaps because the ligands generally
      used, raclopride (RAC) and spiperone (SPI), did not label the same sites. In this
      study, we found that the in vivo binding characteristics of [3H]RAC labeled twice
      as many sites in striatum and olfactory tubercle and [3H]SPI twice as many sites
      in pituitary. 2) The kinetic was much shorter with [3H]RAC than [3H]SPI in
      striatum. 3) RAC, unlike SPI, did not exhibit limbic selectivity. 4) The
      modulation of [3H]RAC and [3H]SPI binding by endogenous DA were diametrically
      opposite: D-amphetamine decreased, and reserpine + alpha-methyl-p-tyrosine
      increased [3H]RAC binding in striatum whereas the opposite occurred with [3H]SPI.
      This distinct binding pattern of [3H]RAC and [3H]SPI suggests that these two
      radioligands do not label the same receptor sites.

PMID- 9029506
TI  - Maturation of receptor proteins in eukaryotic expression systems.
AB  - Transient and stable expression in eukaryotic cells is commonly used to examine
      receptor function. Characterization of the V2 vasopressin receptor synthesized in
      transiently transfected cells revealed the presence of large quantities of
      immature protein and a small fraction of fully mature protein. The immature
      protein was characterized by its sensitivity to endoglycosidase H treatment,
      abnormal migration in SDS PAGE, and a tendency to form aggregates. Prevention of
      protein glycosylation by mutagenesis increased the fraction of mature protein
      produced, but did not eliminate the need for the maturation step. On the other
      hand, stably transfected cells produce almost exclusively mature receptor protein
      with a t1/2 of 6 h, while the immature form has a t1/2 of 20 min. In the absence
      of N-linked glycosylation the t1/2 of the mature V2 receptor in stably
      transfected cells was reduced to 4.5 h. In transient expression experiments the
      immature receptor proteins exhibited a prolonged t1/2 of about 8 h. Comparison of
      the half life of the immature form of the wild type and the R137H mutant V2
      receptor did not reveal differences despite the lower amounts of mutant mature
      receptor detected by binding.

PMID- 9029507
TI  - Canine cardiac digitalis receptors are preserved in congestive heart failure
      induced by rapid ventricular pacing.
AB  - In dogs, it has been reported that acute ischemia or severe and terminal heart
      failure results in a selective reduction of myocardial alpha 3 isoform of Na, K
      ATPase activity. The aim of this study was to evaluate if a similar change in the
      two canine digitalis receptor isoforms occurs following 4 weeks of rapid
      ventricular pacing-induced heart failure without profound necrosis. Heart failure
      was induced in dogs by rapid ventricular pacing (240 beats x min-1). Digitalis
      receptors were quantitated by [3H]-ouabain binding with isolated microsomal
      membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by
      Western blot analysis using specific alpha 1 and alpha 3 polyclonal antibodies.
      In kinetic studies, similar dissociation rates of 19 to 22 x 10(-4) s-1 and 1.3
      to 2.4 x 10(-4) s-1 corresponding to high and low affinity sites respectively,
      were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance
      of alpha 1 isoform in the two groups; however, levels of alpha 3 were increased
      by at least 50% in pacing-induced heart failure animals. In conclusion, heart
      failure selectively modulates the expression of cardiac alpha 3 isoform in dogs.

PMID- 9029508
TI  - Energetic and entropic factors determining binding affinity in protein-ligand
      complexes.
AB  - Understanding of non-covalent interactions in protein-ligand complexes is
      essential in modern biochemistry and should contribute toward the discovery of
      new drugs. The affinity of a ligand toward its receptor falls into a range of 10
      80 kJ/mol. It is related to the binding constant and corresponds to a free
      energy. Accordingly enthalpic and entropic effects determine binding affinity.
      Hydrogen bonds and lipophilic contacts are the most important contributions to
      protein-ligand interactions. They are governed by changes in entropy and
      enthalpy. Solvation and desolvation effects either of the ligand and the protein
      binding site play a key role in the binding process. Prerequisite for a
      quantitative description and subsequently for a prediction of protein-ligand
      interactions is a partitioning in additive group contributions. In many cases,
      this additivity seems to be a good approximation, however, phenomena such as
      conformational pre-organizations give rise for a non-additive behavior.
      Flexibility and mobility of the bound ligand influence binding affinity. The rare
      experiments separating enthalpic and entropic contributions to the binding
      affinity sometimes reveal surprisings results, e.g. the loss of a hydrogen bond
      parallels with a loss in entropy.

PMID- 9029510
TI  - Thermodynamic parameters of ligand-receptor interactions: computation and error
      margins.
AB  - A semiempirical relationship describing the temperature function of ligand
      receptor dissociation constants (Kd), derived from heat capacities of the system
      in equilibrium, is suggested for computation of the standard enthalpy (delta H
      degree) and standard entropy (delta S degree) changes in equilibrium. The use of
      the linear expression (called Gibbs-van't Hoff equation) may lead to inaccurate
      results when heat capacity Cp displays a considerable temperature dependence. The
      accuracy of Kd, delta H degree and delta S degree has been studied by simulation
      experiments. In the case of Kd, deviations of computed from "true" values are
      determined by both the accuracy of experimental data used for its estimation, and
      by the shape of the binding isotherm (for instance, by Hill coefficients or by
      the presence of low affinity sites). As a rule, if errors of bound ligand
      measurements are greater than 20 per cent, Kd estimates ought to be considered as
      less reliable. However, computations of delta H degree and delta S degree that
      use such Kd values, are more correct, probably due to an error compensation. The
      suggested nonlinear temperature function of Kd enables an estimate of the heat
      capacity of the system and its temperature dependence.

PMID- 9029509
TI  - Integrated homology modelling and X-ray study of herpes simplex virus I thymidine
      kinase: a case study.
AB  - Knowledge-based homology modelling together with site-directed mutagenesis,
      epitope and conformational mapping is an approach to predict the structures of
      proteins and for the rational design of new drugs. In this study we present how
      this procedure has been applied to model the structure of herpes simplex virus
      type 1 thymidine kinase (HSV1 TK, HSV1 ATP-thymidine-5'-phosphotransferase, EC
      2.7.1.21). We have used, and evaluated, several secondary structure prediction
      methods, such as the classical one based on Chou and Fastman algorithm, neural
      networks using the Kabsch and Sander classification, and the PRISM method. We
      have validated the algorithms by applying them to the porcine adenylate kinase
      (ADK), whose three-dimensional structure is known and that has been used for the
      alignment of the TKs as well. The resulting first model of HSV1-TK consisted of
      the first beta-strand connected to the phosphate binding loop and its subsequent
      alpha-helix, the fourth beta-strand connected to the conserved FDRH sequence and
      two alpha-helix with basic amino acids. The 3D structure was built using the X
      ray structure of ADK as template and following the general procedure for homology
      modelling. We extended the model by means of COMPOSER, an automatic process for
      protein modelling. Site-directed mutagenesis was used to experimentally verify
      the predicted active-site model of HSV1-TK. The data measured in our lab and by
      others support the suggestion that the FDRH motif is part of the active site and
      plays an important role in the phosphorylation of substrates. The structure of
      HSV1 TK, recently solved in collaboration with Prof. G. Schulz at 2.7 A
      resolution, includes 284 of 343 residues of the N-terminal truncated TK. The
      secondary structures could be clearly assigned and fitted to the density. The
      comparison between crystallographically determined structure and the model shows
      that nearly 70% of the HSV1 TK structure has been correctly modelled by the
      described integrated approach to knowledge based ligand protein complex structure
      prediction. This indicate that computer assisted methods, combined with "manual"
      correction both for alignment and 3D construction are useful and can be
      successful.

PMID- 9029511
TI  - Fluorescence correlation spectroscopy (FCS)--a highly sensitive method to analyze
      drug/target interactions.
AB  - Fluorescence Correlation Spectroscopy (FCS) a new analytical technology, allows
      binding properties to be determined very accurately in biological assays at the
      level of single molecules. At concentrations of > or = 10(-12) M, binding
      constants, on/off-rates, and even reaction/enzyme kinetics can be determined in
      real-time, and in sample volumes as low as 10(-9) microliters. The FCS technology
      can be applied to study molecular and cellular interactions in homogeneous
      assays. Assay times in the range of seconds in combination with nanoliter sample
      volumes allow FCS to be used for high throughput screening to identify new
      pharmaceutical lead structures or new pharmacological targets. FCS is fully
      compatible with standard microtiter plate formats. However, for high throughput
      screening, specially designed sample carriers containing many thousand sub
      microliter sample wells may be used in combination with a nanopipetting and
      sample retrieval system.

PMID- 9029512
TI  - Development of a novel TNF alpha ligand-receptor binding assay for screening
      NATCHEM Libraries.
AB  - The TNF alpha receptor is a major therapeutic target since over production of TNF
      alpha plays a key role in the development of septic shock following bacterial
      infection and has been implicated in the pathogenesis of many inflammatory
      disorders such as rheumatoid arthritis. To screen our NATCHEM Libraries for novel
      natural product inhibitors of this target we have developed a sensitive
      immobilised TNF alpha receptor binding assay based on a commercially available
      recombinant soluble TNF alpha receptor (p55) and [125I]-TNF alpha.

PMID- 9029513
TI  - Drug discovery using receptors that modulate gene expression.
AB  - Cytokines and non-peptidyl small molecules, such as steroid hormones, exert many
      of their effects on cells through rapid regulation of gene expression. This is
      achieved by the activation of different families of latent transcription factors,
      which bind to specific sequences in the promoters of regulated genes. High
      throughput assay systems have been developed based on a detailed molecular
      understanding of these transcriptional regulation processes, and are being used
      as screens for both agonists and antagonists of specific cytokines and hormones.
      The opportunities for the discovery of novel and selective compounds using these
      systems is discussed.

PMID- 9029514
TI  - Orphan receptors and their natural ligands.

PMID- 9029515
TI  - Nomenclature and classification of transmitter receptors: an integrated approach.
AB  - This short assay is an attempt to rationalize an integrated approach to
      transmitter receptor nomenclature and classification based on three criteria:
      structural information (gene structure/amino acid sequence), operational 1
      information (pharmacological/ ligand-defined/recognitory) and transductional
      information (receptor-effector coupling) are proposed to be used when considering
      the naming of existing or newly discovered receptors. It should be recognized
      that none of these criteria has primacy and that in an ideal situation, as much
      information as feasible on these three aspects should be collected before the
      naming of a receptor can be agreed upon.

PMID- 9029524
TI  - A coupled PCR and restriction digest method for the detection and analysis of the
      SV40 regulatory region in infected-cell lysates and clinical samples.
AB  - The polymerase chain reaction (PCR) is an increasingly popular analytical tool
      for the detection of virus sequences in laboratory preparations as well as in
      human clinical samples. In studies involving papovaviruses SV40, BK virus (BKV),
      and JC virus (JCV), one of the primary targets for analysis is the viral
      regulatory region, as that section of the papovavirus genome is distinct. A
      primary concern with PCR-based studies is whether amplified DNA sequences may be
      derived from laboratory contaminants. Recognizing that common sources of PCR
      contamination are the positive control templates, we devised a facile method to
      distinguish between real and false-positive PCR-amplified SV40 regulatory region
      DNAs. SV40 constructs that had been engineered to contain different combinations
      of 72-basepair (bp) enhancer elements and 21-bp repeats, as well as two
      introduced unique restriction enzyme sites, were used as positive control
      templates for PCR amplification. Cleavage of PCR-amplified DNA identifies
      products from the engineered control plasmids. The procedure is rapid, simple and
      cost-effective. We also report that primer sets predicted to be specific for the
      SV40 regulatory region can be used to amplify BKV and JCV regulatory region
      sequences under conditions of reduced stringency.

PMID- 9029525
TI  - Rapid and sensitive genotyping of hepatitis C virus by single-strand conformation
      polymorphism.
AB  - There is an increasing demand for genotyping hepatitis C virus (HCV) isolates due
      to the rapidly expanding list of distinct HCV genotypes and the mounting evidence
      of genotype-specific clinical consequences. We describe an SSCP-based assay for
      determining genotypes in HCV infections. HCV RNA extracted from serum was
      amplified by a sensitive nested-PCR assay producing a 287 bp fragment of the
      conserved 5' non-coding region (NCR) and analysed by non-denaturing
      polyacrylamide gel electrophoresis. Following empirical optimisation of the SSCP
      assay we identified distinct conformation polymorphisms (characteristic band
      patterns) corresponding to types 1a, 1b, 2a, 2b, 2c, 3 and 4 found in the Western
      Australian population. Seventy-three HCV RNA-positive samples were used to
      evaluate the SSCP genotyping assay for accuracy and efficiency by comparison with
      the previously established genotyping methods of manual direct sequencing and
      dideoxy fingerprinting. SSCP genotyping was in concord with control methods while
      performing more rapidly and at a fraction of the cost. Moreover, SSCP detected
      two co-infected samples that were not shown by the control methods. The PCR-SSCP
      assay provides an accurate and rapid method for genotyping of HCV RNA-positive
      samples at the 5' NCR by type-specific sequence polymorphisms which is applicable
      to large-scale screening.

PMID- 9029526
TI  - Development of a quantitative competitive polymerase chain reaction for human
      herpesvirus 8.
AB  - A quantitative competitive polymerase chain reaction (PCR) assay for human
      herpesvirus 8 (HHV8) was developed. The assay uses a competitive internal control
      sequence which differs from the wild type sequence by the presence of an EcoRI
      restriction endonuclease site. The quantitative method was validated by co
      amplifying known amounts of control sequence DNA and wild type DNA, and shown to
      accurately quantify HHV8 within the range of 10(1)-10(6) genome copies (R =
      0.998). The assay was used to quantify HHV8 in sequential blood samples of a
      renal transplant patient diagnosed with Kaposi's sarcoma (KS). A peak viral load
      of 28320 genomes/ml blood was present at diagnosis of KS, which reduced to 13680
      genomes after 2 days and was undetectable 4 months later. Control of HHV8
      replication in this patient parallelled the cessation of immunosuppressive
      therapy.

PMID- 9029528
TI  - Development of an in vitro quantal assay in primary cell cultures for a non
      occluded baculo-like virus of penaeid shrimp.
AB  - An in vitro quantal assay (TCID50) for a non-occluded baculo-like virus isolate
      from naturally infected Penaeus japonicus obtained from China and experimentally
      infected P. stylirostris was developed using primary shrimp lymphoid cell
      cultures in Primaria 24-well tissue culture plates. The virus caused
      cytopathogenic effect (CPE) in the cell cultures as early as 2 day post-infection
      (p.i.). Initially, the cells rounded up and finally detached from the culture
      vessel as the infection progressed. At the present time, there is no established
      quantitative in vitro cell culture protocol for the assay of this baculo-like
      virus which has been reported by our laboratory to be highly pathogenic for P.
      stylirostris and P. vannamei, the two species of penaeid shrimp commercially
      cultured in Hawaii and the Western hemisphere. This quantal assay thus provides a
      simple and convenient method for the detection and assay of infectious virus in
      cultured penaeid shrimp.

PMID- 9029527
TI  - High level expression of the major antigenic African swine fever virus proteins
      p54 and p30 in baculovirus and their potential use as diagnostic reagents.
AB  - At present, the eradication of African swine fever (ASF) in affected countries is
      based only on an efficient diagnosis program because of the absence of an
      available vaccine. The highly antigenic ASF virus proteins p54 and p30, encoded
      by genes E183L and CP204L respectively, were expressed in baculovirus for
      diagnostic purposes. A sequence comparison analysis of these genes from different
      field virus strains which are geographically diverse and isolated in different
      years, revealed that both genes are completely conserved among the isolates.
      Partially purified baculovirus-expressed proteins were used in ELISA and Western
      blot for ASF antibody detection in sera from experimentally inoculated pigs and
      field sera from ASF innaparent carriers. These comparative analyses showed that
      p54 presents better reactivity than p30 in Western blot. However, recombinant p30
      was more efficient for antibody detection by ELISA, improving the discrimination
      between positive and negative sera by this technique. These data suggest the
      convenience of using p30 as ELISA antigen, while p54 should be the selected
      antigen for ASF virus antibody detection by Western blot. The combined use of
      both antigens for serodiagnosis of ASF disease will improve the sensitivity of
      innaparent carriers detection, facilitating also the interpretation of the tests,
      and eliminating the use of ASF virus in antigen production.

PMID- 9029529
TI  - Detection and identification of ruminant and porcine pestiviruses by nested
      amplification of 5' untranslated cDNA regions.
AB  - Based on published gene sequences of bovine viral diarrhoea virus (BVDV) type I
      and classical swine fever virus (CSFV), genus- and species-specific primers were
      designed to detect and identify pestivirus cDNA sequences in a nested polymerase
      chain reaction (PCR). The PCR primers were validated using cDNA synthesized from
      146 pestivirus isolates, comprising representatives of all four so far described
      genotypes (BVDV type I, BVDV type II, CSFV and border disease virus), as well as
      others of uncertain classification. PCR products of the predicted size were
      amplified from all viruses with the genus-specific primers. All 53 cattle
      isolates, including 5 typed antigenically as BVDV type II were amplified by the
      internal BVDV-specific primers, but not the CSFV-specific primers. The same
      result was found for other BVDV type I and II viruses isolated from sheep and
      pigs. Seventy-seven CSF viruses were amplified by their respective internal
      primers. Available information strongly indicate that 4 CSF viruses also
      amplified by the BVDV-specific primers had been contaminated with BVDV in cell
      cultures. Border disease viruses were mostly not detected by the BVDV-specific
      primers, but were detected weakly by the CSFV-specific primer pair. Using carrier
      RNA for extraction of viral RNA, the sensitivity of detection of the single and
      nested PCR was, respectively, 5 and 50 times higher than obtained with a cell
      culture assay. The RT-PCR also detected BVDV in all of 15 commercial batches of
      fetal calf serum examined, and verified three earlier diagnoses of CSFV by
      detecting specific gene sequences in 30 year old frozen archival organ samples.

PMID- 9029530
TI  - Rescue of measles virus using a replication-deficient vaccinia-T7 vector.
AB  - A system which allows the reconstitution of measles virus (MV) from cloned cDNA
      is described. The severely host cell restricted vaccinia vector MVA-T7 expressing
      bacteriophage T7 RNA polymerase was used to generate full-length antigenomic MV
      RNA and simultaneously the mRNAs encoding the viral N, P and L proteins in order
      to produce replicationally and transcriptionally active nucleocapsids. The
      functionality of the N, P and L proteins was demonstrated first by their ability
      to rescue MV specific subgenomic RNAs. Assembly and budding of reconstituted MV
      was shown by syncytia formation and subsequently by virus isolation. The
      inability of MVA-T7 to produce progeny virus in most mammalian cells circumvents
      the necessity to separate the reconstituted MV from the MVA-T7 helper virus.
      Since all components are expressed transiently, this system is especially
      suitable for studying the functions of N, P and L. Furthermore, it is useful for
      investigating later steps in the MV life cycle.

PMID- 9029531
TI  - Development of a nucleic acid capture probe with reverse transcriptase-polymerase
      chain reaction to detect poliovirus in groundwater.
AB  - There is a need to develop a practical method for the detection of viral
      contaminates in water supplies. In this study, poliovirus was used as a model to
      develop a nucleic acid capture technique. This technique was used to recover
      viral RNA from concentrated groundwater samples. Poliovirus RNA was isolated
      using magnetic bead technology. A biotinylated oligonucleotide probe was
      hybridized to poliovirus-RNA in solution. Streptavidin coated magnetic beads were
      then added to isolate the RNA-oligonucleotide hybrid. The procedure allows for
      the recovery of viral RNA suitable for amplification by reverse transcription
      polymerase chain reaction (RT-PCR). This nucleic acid capture system was
      effective in both concentrating, and purifying poliovirus RNA while removing
      environmental RT-PCR inhibitors. A detection sensitivity of one plaque forming
      unit (PFU) in 250 microliters of a concentrated environmental sample was
      routinely attained. This was the same detection level found with seeded purified
      water. It was shown that the sensitivity of nucleic acid capture RT-PCR was
      significantly greater than direct RT-PCR, when applied to environmental samples.
      The amplified product was sequenced to ensure specificity. Furthermore, this
      technique is rapid, reliable and can be readily adapted to detect other viral
      pathogens.

PMID- 9029533
TI  - Two PBMC-based neutralization assays depict low reactivity of both anti-V3
      monoclonal antibodies and immune sera against HIV-1 primary isolates.
AB  - The neutralizing activity of anti-V3 monoclonal antibodies (MAbs) and anti-HIV-1
      immune sera was tested against HIV-1 laboratory strains and African primary
      isolates. Neutralization was investigated in Phytohaemagglutinin (PHA)-stimulated
      peripheral blood mononuclear cell (PBMC) cultures by means of two distinct viral
      titer reduction assays. In these assays, virus was detected by means of either
      p24 antigen measurement using ELISA or HIV provirus synthesis using PCR,
      respectively. Anti-V3 MAbs and anti-HIV-1 immune sera neutralized efficiently the
      homologous laboratory HIV-1 strains used for eliciting immune response but showed
      no neutralizing activity against most primary isolates. The two neutralization
      assays used provided similar results. However, a PCR-based assay circumvented the
      limitations due to low levels of virus replication. The mechanism of resistance
      of the primary isolates to neutralizing antibodies was complex and was not simply
      predicted by partial sequence determination of the epitopes. This points out the
      need for reliable neutralization assays of HIV-1 primary isolates in order to
      evaluate the role of humoral immunity during HIV-1 infection and for future
      vaccine strategies.

PMID- 9029532
TI  - Comparison between cytomegalovirus promoter and elongation factor-1 alpha
      promoter-driven constructs in the establishment of cell lines expressing
      hepatitis C virus core protein.
AB  - The establishment of stable cell lines expressing the hepatitis C virus (HCV)
      core protein may be important for studies of HCV pathogenesis. Human and mouse
      cell lines were generated expressing the HCV core protein using expression
      vectors driven by either the cytomegalovirus (CMV) or elongation factor-1 alpha
      (EF-1 alpha) promoters. Following transient transfection, HCV core protein was
      expressed in all cell lines. However, stable human hepatocellular carcinoma (HCC)
      and murine myeloma cell lines expressing the HCV core protein were only
      established using constructs driven by the EF-1 alpha promoter. In contrast,
      stable expression of the hepatitis B virus (HBV) middle envelope protein (MHBs)
      was obtained successfully in these cell lines using an expression vector driven
      by the CMV promoter. Inhibitory activity of the first 69 amino acids of the HCV
      core protein on the CMV promoter was found by using chimeric MHBs/HCV core
      protein constructs. Growth of cloned cell lines expressing the HCV core protein
      was slower than that of nonexpressing cell lines. However, morphological changes
      and cell death were not observed in the stable cell lines expressing HCV core
      protein. These results indicate that the HCV core protein was not directly
      cytotoxic to HCC and myeloma cell lines but that specific promoter elements are
      required to establish stable expression of the nucleocapsid structural protein.

PMID- 9029535
TI  - Simple hand-held devices for the efficient infection of plants with viral
      encoding constructs by particle bombardment.
AB  - An efficient method for infection of plants with a cloned potyvirus by particle
      bombardment has been described (Gal-On et al., 1995). A simplified method is
      described now whereby a vaccuum chamber and helium propulsive gas are not
      required to achieve a high efficiency of infection. The new device-the 'HandGun'-
      is hand-held, and easily constructed from readily available materials. With this
      technique it is possible to bombard soft plants and seedings that do not survive
      particle bombardment by other devices. bombardment of C. pepo plants with a full
      length clone of zucchini yellow mosaic potyvirus results in approximately 100%
      infection at 100 pg cDNA per plant using air or helium to propel the
      microprojectiles. The HandGun is 10(5)-fold more efficient than mechanical
      inoculation. Tungsten and gold were found to be the most efficient materials
      tested for use as microprojectiles. Crude extracts of plasmids from E. coli were
      found to be effective, as well as column-purified cDNA. A functional, simple
      version of the HandGun--'the Blowpipe'--was also constructed, which does not
      require an electrically controlled valve. Plants can be inoculated with plant
      viruses from sap with the HandGun.

PMID- 9029534
TI  - Quasispecies analysis in hepatitis C virus infection by fluorescent single strand
      conformation polymorphism.
AB  - Hepatitis C virus (HCV) results frequently in chronic hepatitis and its sequelae
      liver cirrhosis and hepatocellular carcinoma. Interferon-alpha is at present the
      most effective treatment, resulting in a sustained response in about 20-25% of
      patients. HCV genotype, titer and quasispecies determine the success of
      treatment. In this study, fluorescent single strand conformation polymorphism (f
      SSCP) was evaluated for the analysis of HCV quasispecies. Two sera from a
      chronically HCV-infected patient, obtained 6 years apart, were examined. The
      hypervariable region I (HVRI) of the HCV genome was amplified by reverse
      transcription and PCR. The PCR products were cloned and sequenced or fluorescein
      labeled and subjected to f-SSCP. Both methods demonstrated a single HCV species
      in the early serum and multiple quasispecies in the late serum. Single clones of
      the heterogeneous virus population were used to optimize conditions for f-SSCP.
      The most important factors were the gel temperature and virus titer. At the
      optimal running temperature one base exchange in 218 bases was detectable. Repeat
      extractions and amplifications gave identical results. Dilution of the serum
      containing multiple quasispecies resulted in a 'loss' of species. Provided the
      running temperature is optimal and virus titer is sufficient, f-SSCP is shown to
      be fast and reliable for HCV quasispecies analysis.

PMID- 9029536
TI  - Tomographic imaging of the angular-dependent coherent-scatter cross section.
AB  - A new special-purpose computed tomographic (CT) imaging system is described which
      produces images based on measurements of the low-angle (0-10 degrees) x-ray
      diffraction properties of an object. Low-angle scatter in the diagnostic x-ray
      energy range is dominated by coherent scatter, and the system uses first
      generation CT geometry to acquire a diffraction pattern for each pencil beam. The
      patterns are used to reconstruct a series of images which represent the coherent
      scatter intensity at a series of scatter angles. To demonstrate the potential of
      coherent-scatter CT (CSCT), the scanner has been built and used to image a
      phantom consisting of a water-filled Lucite cylinder containing rods of
      polyethylene, Lucite, polycarbonate, and nylon. In this paper, the system is
      described and a sequence of CSCT images of this phantom is shown. Coherent
      scatter cross sections of these materials are generated for each pixel from this
      sequence of images and compared with cross sections measured separately. The
      resulting excellent agreement shows that the angular-dependent coherent-scatter
      cross section can be accurately imaged in a tomographic slice through an object.
      These cross sections give material-specific information about the object. The
      long-term goal of this research is to make measurements of bone-mineral content
      for every pixel in a tomographic slice.

PMID- 9029537
TI  - Investigation of the line-pair pattern method for evaluating mammographic focal
      spot performance.
AB  - The latest American College of Radiology (ACR) Mammography Quality Control Manual
      contains a new method for evaluating focal spot performance, which this paper
      refers to as the "line-pair pattern test." The ACR describes a variety of methods
      for performing this test, and does not advocate one method over another. The
      authors of this paper conducted an investigation to compare the optional ways for
      performing the test. Resolution measurements were obtained using a prototype line
      pair resolution phantom imaged with a GE DMR mammography unit. Measurements were
      made with the line-pair pattern 4.5 cm above the breast support platforms in both
      conventional (contact) and magnification geometries. Both 4.5 cm of air and
      Lucite were tested as attenuators between the line-pair pattern and the breast
      support platform. Image receptors that were employed included film alone, screen
      film, and screen-film that was not allowed to wait the recommended 15 min before
      exposure. kVp was varied as was the orientation of the line-pair pattern relative
      to the chest wall. For the air attenuator case, the screen degraded the measured
      resolution by 1-3 lp/mm when compared to the direct film. The Lucite attenuator
      reduced the resolution by an additional 1 1p/mm. Increasing kVp improved the
      resolution slightly for the conventional mode, but decreased it slightly for the
      magnification mode. Based upon the results of this study, recommendations are
      made for improving the test protocol. For a test of focal spot performance, one
      should use the no-attenuation with direct film detector setup. For a measure of
      the resolution of the entire imaging chain, one should use the Lucite attenuator
      with screen-film detector setup.

PMID- 9029538
TI  - Comparison of eye position versus computer identified microcalcification clusters
      on mammograms.
AB  - The purpose of this study was to compare identifications of microcalcification
      clusters on mammograms by a computerized detection scheme and by human observers
      having their eye position recorded. Eighty digitized mammograms (half with a
      subtle microcalcification cluster) were analyzed by a computerized detection
      scheme and then were read from laser-printed films by six mammographers while eye
      position was recorded. The computer had 83% true positives with a false-positive
      rate of 0.5 per image. The true positives of the radiologists ranged from 78% to
      90%, with false-positive rates ranging from 0.03 to 0.20. Locations of true and
      false positives identified by computer and by the human were compared. All but 5%
      of the true clusters were identified by either the computer, human, or by both.
      Here 10% of the clusters were detected by only the computer, and 11% were missed
      by the computer but detected by at least one radiologist. False positives were of
      three types: identified by computer only, by the human reader only, or by both.
      Eye-position data indicated significant differences in dwell time between both
      true-positive and false-positive locations reported by the radiologist versus the
      computer detections. A follow-up analysis indicated that microcalcification
      clusters and false positives were judged to have more identifiable
      characteristics of true calcifications and were associated with longer gaze
      durations than those with fewer microcalcification characteristics. In general,
      the computer was able to detect clusters judged to have few or no features that
      the radiologists were not able to detect. Comparison of computer versus human
      identification of microcalcification clusters may be useful for improving
      computerized detection schemes to serve as clinical aids to mammographers, and
      for understanding what image features lead to false-positive decisions for both
      the computer and the human reader.

PMID- 9029539
TI  - Automated three-dimensional registration of magnetic resonance and positron
      emission tomography brain images by multiresolution optimization of voxel
      similarity measures.
AB  - Approaches using measures of voxel intensity similarity are showing promise in
      fully automating magnetic resonance (MR) and positron emission tomography (PET)
      image registration in the head, without requiring extraction and identification
      of corresponding structures. In this paper a method of multiresolution
      optimization of these measures is described and five alternative measures are
      compared: cross correlation, minimization of corresponding PET intensity
      variation, moments of the distribution of values in the intensity feature space,
      entropy of the intensity feature space and mutual information. Their ability to
      recover registration is examined for ten clinically acquired image pairs with
      respect to the size of initial misregistration, the precision of the final
      result, and the accuracy assessed by visual inspection. The mutual information
      measure proved the most robust to initial starting estimate, successfully
      registering 98.8% of 900 trial misregistrations. Success is defined as providing
      a visually acceptable solution to a trained observer. A high resolution search
      (1/16 mm step size) of 30 trial misregistrations showed that optimization using
      the mutual information measure provided solutions with 0.13 mm, 0.11 mm and 0.17
      mm standard deviations in the three Cartesian axes of the translation vector and
      0.2 degree, 0.3 degree and 0.2 degree standard deviations for rotations about the
      three axes. The algorithm takes between 4 and 8 minutes to run on a typical
      workstation, including visual inspection of the result.

PMID- 9029540
TI  - X-ray imaging technique for in vitro tissue composition measurements using
      saline/iodine displacement: technique optimization.
AB  - An in vitro radiographic technique which uses saline/iodine displacement has been
      developed to study the thickness of bone-equivalent and soft-tissue-equivalent
      materials within atherosclerotic plaques in arterial specimens which have been
      cut open longitudinally and laid flat. Results concerning the optimization of the
      imaging parameters are presented and discussed. The technique consists of imaging
      arterial specimens under two different conditions: (1) when it is immersed in an
      isotonic saline solution, to estimate the calcium content, and (2) when it is
      immersed in a concentrated iodine solution, to estimate the total thickness of
      the specimen. Calibration step wedges made out of bone-mimicking and soft-tissue
      mimicking materials are imaged simultaneously to generate calibration curves
      which are used to convert the radiographs into bone-equivalent and soft-tissue
      equivalent thickness images. The optimal spectral parameters were determined to
      be 45 and 100 kVp for the saline and the iodine images, respectively, with a
      significant amount of added filtration for both images. Inherent systematic
      inaccuracies due to (1) the nonidealities due to linear attenuation coefficient
      mismatch between tissue and calibration materials and (2) beam hardening due to
      heel effect are determined theoretically, and can be used to correct a set of
      bone-equivalent and the soft-tissue-equivalent images to within +/- 6 microns
      with an ideal, noise-free imaging system.

PMID- 9029541
TI  - Empirical investigation of the signal performance of a high-resolution, indirect
      detection, active matrix flat-panel imager (AMFPI) for fluoroscopic and
      radiographic operation.
AB  - Signal properties of the first large-area, high resolution, active matrix, flat
      panel imager are reported. The imager is based on an array of 1536 x 1920 pixels
      with a pixel-to-pixel pitch of 127 microns. Each pixel consists of a discrete
      amorphous silicon n-i-p photodiode coupled to an amorphous silicon thin-film
      transistor. The imager detects incident x rays indirectly by means of an
      intensifying screen placed over the array. External acquisition electronics send
      control signals to the array and process analog imaging signals from the pixels.
      Considerations for operation of the imager in both fluoroscopic and radiographic
      modes are detailed and empirical signal performance data are presented with an
      emphasis on exploring similarities and differences between the two modes.
      Measurements which characterize the performance of the imager were performed as a
      function of operational parameters in the absence or presence of illumination
      from a light-emitting diode or x rays. These measurements include
      characterization of the drift and magnitude of the pixel dark signal, the size of
      the pixel switching transient, the temporal behavior of pixel sampling and the
      implied maximum frame rate, the dependence of relative pixel efficiency and pixel
      response on photodiode reverse bias voltage and operational mode, the degree of
      linearity of pixel response, and the trapping and release of charge from
      metastable states in the photodiodes. In addition, X-ray sensitivity as a
      function of energy for a variety of phosphor screens for both fluoroscopic and
      radiographic operation is reported. Example images of a line-pair pattern and an
      anthropomorphic phantom in each mode are presented along with a radiographic
      image of a human hand. General and specific improvements in imager design are
      described and anticipated developments are discussed. This represents the first
      systematic investigation of the operation and properties in both radiographic and
      fluoroscopic modes of an imager incorporating such an array.

PMID- 9029542
TI  - Empirical and theoretical investigation of the noise performance of indirect
      detection, active matrix flat-panel imagers (AMFPIs) for diagnostic radiology.
AB  - Noise properties of active matrix, flat-panel imagers under conditions relevant
      to diagnostic radiology are investigated. These studies focus on imagers based
      upon arrays with pixels incorporating a discrete photodiode coupled to a thin
      film transistor, both fabricated from hydrogenated amorphous silicon. These
      optically sensitive arrays are operated with an overlying x-ray converter to
      allow indirect detection of incident x rays. External electronics, including gate
      driver circuits and preamplification circuits, are also required to operate the
      arrays. A theoretical model describing the signal and noise transfer properties
      of the imagers under conditions relevant to diagnostic radiography, fluoroscopy,
      and mammography is developed. This frequency-dependent model is based upon a
      cascaded systems analysis wherein the imager is conceptually divided into a
      series of stages having intrinsic gain and spreading properties. Predictions from
      the model are compared with x-ray sensitivity and noise measurements obtained
      from individual pixels from an imager with a pixel format of 1536 x 1920 pixels
      at a pixel pitch of 127 microns. The model is shown to be in excellent agreement
      with measurements obtained with diagnostic x rays using various phosphor screens.
      The model is used to explore the potential performance of existing and
      hypothetical imagers for application in radiography, fluoroscopy, and mammography
      as a function of exposure, additive noise, and fill factor. These theoretical
      predictions suggest that imagers of this general design incorporating a CsI: Tl
      intensifying screen can be optimized to provide detective quantum efficiency
      (DQE) superior to existing screen-film and storage phosphor systems for general
      radiography and mammography. For fluoroscopy, the model predicts that with
      further optimization of a-Si:H imagers, DQE performance approaching that of the
      best x-ray image intensifier systems may be possible. The results of this
      analysis suggest strategies for future improvements of this imaging technology.

PMID- 9029543
TI  - Evaluation of a commercial three-dimensional electron pencil beam algorithm.
AB  - Results from beta testing of a commercially available three-dimensional electron
      pencil beam algorithm (CMS FOCUS, Computerized Medical Systems, Inc. St. Louis,
      MO) are reported. Straight on beams were evaluated at normal and extended
      distances, and obliquely incident beams at angles up to 40 degrees. Shaped
      electron fields with small circular cutouts, and narrow elongated, centered and
      offcentered, rectangular field shapes were investigated. Slab inhomogeneities
      were studied for lung and bone equivalent material, and isodose distributions for
      small inhomogeneities of these materials were compared with film and TLD
      measurements. All tests reported here were performed with electrons 6, 12, and 20
      MeV from a Cl-1800 accelerator.

PMID- 9029544
TI  - Reporting and analyzing dose distributions: a concept of equivalent uniform dose.
AB  - Modern treatment planning systems for three-dimensional treatment planning
      provide three-dimensionally accurate dose distributions for each individual
      patient. These data open up new possibilities for more precise reporting and
      analysis of doses actually delivered to irradiated organs and volumes of
      interest. A new method of summarizing and reporting inhomogeneous dose
      distributions is reported here. The concept of equivalent uniform dose (EUD)
      assumes that any two dose distributions are equivalent if they cause the same
      radiobiological effect. In this paper the EUD concept for tumors is presented,
      for which the probability of local control is assumed to be determined by the
      expected number of surviving clonogens, according to Poisson statistics. The EUD
      can be calculated directly from the dose calculation points or, from the
      corresponding dose-volume distributions (histograms). The fraction of clonogens
      surviving a dose of 2 Gy (SF2) is chosen to be the primary operational parameter
      characterizing radiosensitivity of clonogens. The application of the EUD concept
      is demonstrated on a clinical dataset. The causes of flattening of the observed
      dose-response curves become apparent since the EUD concept reveals the finer
      structure of the analyzed group of patients in respect to the irradiated volumes
      and doses actually received. Extensions of the basic EUD concept to include
      nonuniform density of clonogens, dose per fraction effects, repopulation of
      clonogens, and inhomogeneity of patient population are discussed and compared
      with the basic formula.

PMID- 9029545
TI  - Electron dose calculations using the Method of Moments.
AB  - The Method of Moments is generalized to predict the dose deposited by a
      prescribed source of electrons in a homogeneous medium. The essence of this
      method is (i) to determine, directly from the linear Boltzmann equation, the
      exact mean fluence, mean spatial displacements, and mean-squared spatial
      displacements, as functions of energy; and (ii) to represent the fluence and dose
      distributions accurately using this information. Unlike the Fermi-Eyges theory,
      the Method of Moments is not limited to small-angle scattering and small angle of
      flight, nor does it require that all electrons at any specified depth z have one
      specified energy E(z). The sole approximation in the present application is that
      for each electron energy E, the scalar fluence is represented as a spatial
      Gaussian, whose moments agree with those of the linear Boltzmann solution.
      Numerical comparisons with Monte Carlo calculations show that the Method of
      Moments yields expressions for the depth-dose curve, radial dose profiles, and
      fluence that are significantly more accurate than those provided by the Fermi
      Eyges theory.

PMID- 9029546
TI  - Electron arc dose distributions as a function of beam energy.
AB  - The characteristic angle-beta concept provides a simple semiempirical method for
      determination of dose distributions in electron arc therapy. Initially, the
      method required a set of measured radial depth dose distributions for each
      electron beam energy used for arc therapy. In this paper, we report an extension
      of the angle-beta concept that enables the determination of arc therapy depth
      doses for an arbitrary electron energy from the known set of depth dose data at a
      reference energy. Depth dose distributions of stationary and arc electron beams
      have been studied in the energy range from 9 to 18 MeV. The stationary electron
      beams used for electron arc therapy were collimated by photon collimators only,
      no secondary collimation was used in our experiments. For stationary electron
      beams and for arc electron beams with a given characteristic angle beta, the
      depths of dose maximum as well as the depths of a given percentage depth dose
      beyond the depth of dose maximum are linearly proportional to the mean incident
      electron energy. This simple geometrical and dosimetric relationship increases
      the potential usefulness of the angle-beta concept in clinical electron arc
      therapy.

PMID- 9029547
TI  - Exceptional increases in electron cone output as the backup diaphragms are
      opened.
AB  - Some linac manufacturers provide cones for defining circular electron fields.
      During commissioning of one of our new radiotherapy units, we noted that the
      output of these cones has a strong dependence on the diaphragm opening that
      precedes the cone. In particular, for the 8 MeV beam, the output of a 3 cm
      diameter cone increased by more than a factor of 2 as the diaphragm was opened
      from 5 x 5 to 20 x 20 cm. One concludes that the particular mechanical design
      results in an output factor dependency that is exceptional when compared to the
      data presented in standard texts such as Khan's "The Physics of Radiation
      Therapy." The importance of quality assurance and communications with the
      manufacturer is underscored by this example.

PMID- 9029548
TI  - Shielding for thermal neutrons.
AB  - The problem of calculating the neutron capture gamma-ray dose rate due to thermal
      neutron capture in a boron or cadmium rectangular shield is considered. An
      example is given for shielding for a door at the exit of medical accelerator room
      maze in order to determine the optimum location of lead relative to the borated
      polyethylene.

PMID- 9029549
TI  - beta-Cyano-L-alanine toxicity: evidence for the involvement of an excitotoxic
      mechanism.
AB  - The legume Vicia sativa (common vetch) harbors the neurotoxic nonprotein amino
      acid beta-cyano-L-alanine (BCLA) and its gamma-glutamyl derivative. BCLA elicits
      hyperexcitability, convulsions, and rigidity in chicks and rats after oral or
      intraperitoneal administration, but the mechanism of its action is unknown. The
      effect of different concentrations of BCLA (0.075-10.0 mM) has been investigated
      in an organotypic tissue culture system. BCLA concentrations of 0.075 and 0.60 mM
      had no effect, even up to 6 hr. No changes were observed in cultures treated with
      1 mM BCLA for 4 hr. BCLA (2.0-10.0 mM) induces concentration-dependent changes in
      the explants. The explants display neurona vacuolation, chromatin, clumping, and
      dense shrunken cells, a pathological response generally seen with excitotoxin. MK
      801 (35 microM), which blocks the open ion channel associated with the N-methyl-D
      aspartate (NMDA) class of glutamate receptors, attenuates the neurotoxic property
      of BCLA, while the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (10
      20 microM), provides no significant protection. Treatment of isolated mouse brain
      mitochondria with up to 5 mM BCLA had no inhibitory effect on the activity of
      NADH dehydrogenase (complex I) or cytochrome or oxidase (complex IV), a cyanide
      sensitive enzyme. These results suggest that the neurotoxicity of BCLA (or
      derivative) is mediated directly or indirectly through NMDA receptors.

PMID- 9029550
TI  - Transformation of the mycotoxin ochratoxin A in plants: 1. Isolation and
      identification of metabolites formed in cell suspension cultures of wheat and
      maize.
AB  - The metabolism of the mycotoxin ochratoxin A in plant cells was investigated
      using cell suspension cultures of wheat and maize. A number of metabolites were
      detected by HPLC-chromatography with fluorescence detection. The main metabolites
      were ochratoxin alpha, ochratoxin A methyl ester, two isomers of
      hydroxyochratoxin A, and the glucosides and methyl esters of both
      hydroxyochratoxin A isomers. The compounds were isolated by TLC and preparative
      HPLC and identified by mass spectrometry and specific enzymic reactions.

PMID- 9029551
TI  - Complex association and dissociation kinetics of brevetoxin binding to voltage
      sensitive rat brain sodium channels.
AB  - Brevetoxins bind with high affinity to the voltage-sensitive sodium channel and
      cause nerve cell depolarization and increased sodium ion conductance. Using 0.6
      nM tritium-labeled brevetoxin-3 and freshly prepared synaptosomes from fresh or
      frozen rat brain, binding results at 6 degrees C fit well to a curve for 2-phase
      association with 65% of the binding in the rapid phase and t1/2 values of 11 and
      74 min for the rapid and slow phases, respectively. Both phases were accelerated
      at higher toxin concentrations, binding of 9 nM brevetoxin-3 (PbTx-3) was close
      to equilibrium within 1 hr. The slow phase was not apparent when binding was done
      at 20 degrees C or when binding was done at 6 degrees C after the membrane sample
      had been preincubated at 4 degrees C for 1 day or at 22 degrees C for 1 hr. The 2
      phase nature of association was not affected by substitution of KCl for choline
      chloride in the assay medium to produce sodium channel in the inactive state.
      Dissociation kinetics at 6 degrees C were also complex; the results fit well to a
      2-phase curve with 55% of the dissociation in the rapid phase and t1/2 values of
      13 and 64 min for the rapid and slow phases, respectively. The 2-phase nature did
      not change significantly after preincubation at 4 degrees C for 1 day. However,
      dissociation at 20 degrees C was rapid and fit a curve for 1-phase dissociation
      with a t1/2 of 2-6 min. At higher concentrations of PbTx-3, the binding is
      further complicated by the presence of 2-4 low-affinity binding sites with Kd
      values near 700 nM. In conclusion the association and dissociation of PbTx-3 with
      sodium channel from rat brain are complex processes that may involve changes in
      sodium channel conformation or interactions with other membrane (or membrane
      associated) components.

PMID- 9029552
TI  - Survey of microcystins in environmental water by a highly sensitive immunoassay
      based on monoclonal antibody.
AB  - By using a highly sensitive enzyme-linked immunosorbent assay (ELISA) based on a
      monoclonal antibody, microcystin (MC) concentration was analyzed in environmental
      water samples (total, 134), collected in 1993-1995 from ponds, lakes, reservoirs,
      and rivers in Japan, Thailand, Germany, and Portugal. MCs detected in the water
      samples filtered over a glass filter were designated as free MCs, and those
      samples that were freeze-thawed twice before the filtration were designated as
      total MCs. MCs (> 50 pg/ml) were detected in 14 of 24 samples collected from the
      lakes that were used as recreation and water supply in Japan in different
      regions. In the MC-positive samples, the concentration of free MCs was only a few
      percentages of the total MCs, indicating that the most part of MCs found in the
      water samples was present in algal cells. An additional trial on 33 samples
      collected continuously from Lake Inbanuma, Japan, during June-September 1994-1995
      revealed that the total MCs were in a range of 52-52,000 pg/ml. In Chiang Mai,
      Thailand, 6 of 10 samples were positive, with the mean and highest of 161 and 354
      pg/ml, respectively. In the Frankfurt area. Germany, 4 of 10 and 7 of 8 samples
      collected in the same lakes for recreation in July 1993 and November-December
      1994 showed the presence of MCs, with their mean and highest values of 257 and
      407 pg/ml, respectively. Another survey of MCs in dense bloomed samples collected
      with plankton net revealed a contamination of MCs up to 36,000 pg/ml. In
      Portugal, 28 of 29 samples from 4 lakes, 20 rivers, and 5 reservoirs were
      positive for MCs, with the respective means of 13,664, 11,048, and 2,278 pg/ml.
      These data indicated that MCs contaminate environmental water in ponds, rivers,
      lakes, and reservoirs worldwide. The present ELISA is considered to be a reliable
      tool for the mass monitoring and risk assessment of MCs in water supplies.

PMID- 9029553
TI  - Detection and identification of microcystins in the drinking water of Haimen
      City, China.
AB  - Cyanobacterial toxins, microcystins, have a potent tumor-promoting activity. We
      investigated the level of microcystins in drinking water collected from 1992 to
      1994 in Haimen City, China, where people who drink pond ditch water usually
      incurred a high incidence rate of hepatocellular carcinoma compared with those
      who drink well water. High-performance liquid chromatography, liquid
      chromatography/mass spectrometry (LC/MS), and protein phosphatase inhibition
      assay (pp assay) were used to identify and quantify the microcystins. Microcystin
      LR and [D-Asp3]microcystin LR were detected in 2 of 50 samples at a concentration
      less than 100 ng/L by LC/MS in 1992. Although no microcystins were found by the
      chemical method in 1993, 6 of 7 samples except for 3 tap water samples showed an
      approximate amount of 100 ng/L by using the pp assay in 1994. The obtained
      results supported the epidemiological results reported by Yu.

PMID- 9029554
TI  - Development of a new method for the analysis of sphinganine and sphingosine in
      urine and tissues.
AB  - The fumonisins are inhibitors of de novo sphingolipid biosynthesis in vitro and
      in vivo and thus possibly interfere with the regulation of cell growth,
      differentiation, and neoplastic transformation. In addition, the ratio of free
      sphinganine (Sa) to free sphingosine (So) has been proposed as a marker of
      exposure for animals or humans consuming feed or food contaminated by these
      toxins. A method to analyze these sphingolipid bases has been proposed [Merrill
      et al., 1988: Anal Biochem 171:373-381; Riley et al., 1994a: JAOAC 77:533-540]
      but involves numerous steps and consequently is not ideally suited to the
      analysis of large numbers of samples, as is often required in epidemiological
      studies. A new method was therefore developed for the analysis of the Sa/So ratio
      in tissues as well as human and rat urine. Briefly, the method involves isolation
      of exfoliated cells from as little as 0.5 ml of rat urine or 2 ml of human urine
      followed by a rapid and efficient extraction of sphingolipid bases in ethyl
      acetate, an optimized derivatization step with o-phthaldialdehyde and a high
      pressure liquid chromatography separation on a 250 mm x 4.6 mm. 5 microns
      Kromasil C18 column, with a 4-step phosphate buffer/methanol gradient.
      Fluorescence was monitored at 340 nm excitation, 455 nm emission, and retention
      times for So, Sa, and C-20 Sa were about 11, 14, and 22 min, respectively. The
      method was adapted to tissue analysis by partially digesting approximately 30 mg
      tissue with trypsin to permit isolation of a cell pellet before extraction of the
      sphingolipids as described above. The method was applied to the analysis of So
      and Sa in urines and tissues of fumonisin B1 (FB1) treated and untreated male
      BDIV rats. The Sa/So ratio in urine of untreated rats varied from 0.1 to 0.7, and
      for treated rats (between 1-5 mg FB1/kg body weight daily by gavage), the ratio
      was between 1.2-10. In kidney, the ratio was 0.1 in control rats and varied from
      4 to 10.3 in treated rats. In human urine, measurements could easily be made in 2
      ml of urine in females, but in males much larger volumes were required due to the
      low levels of sphingolipid bases.

PMID- 9029555
TI  - Mycotoxin fumonisin B1 stimulates nitric oxide production in a murine macrophage
      cell line.
AB  - Fumonisin B1 (FB1), a mycotoxin, is a common fungal contaminant of corn and corn
      products. This sphingolipid-like compound causes a variety of animal diseases and
      is a suspected human carcinogen. Cellular targets of FB1 include hepatocytes and
      renal and immune cells. The effects of FB1 on nitric oxide (NO) production
      induced by lipopolysaccharide (LPS) were investigated in the present study by
      using a murine macrophage cell line as a model system. Stimulation of NO
      production was observed for increasing concentrations of FB1 (1, 10, and 100
      microM) and either 0.005 or 0.01 microgram/ml LPS. Although with an increasing
      dose of FB1 the total protein content decreased for the stimulated and the
      unstimulated cells, the NO production remained elevated for the stimulated cells.
      It can be hypothesized that the potentiation of the LPS-dependent NO production
      by FB1 treatment could be due to direct interaction between FB1 and NO synthases
      and LPS receptors or to a disrupted sphingolipid metabolism.

PMID- 9029632
TI  - Identifying treatments that halt progression of pulmonary disease in cystic
      fibrosis.
AB  - Rapid progress in cystic fibrosis research affords the possibility of halting the
      progress of the lung disease. We used data from 215 patients who had sputum
      cultures negative for Burkholderia cepacia, at least one outpatient pulmonary
      function test during 1990, and at least one test a year later to estimate the
      number of subjects and study duration required to demonstrate that a hypothetical
      treatment reduces the rate of decline of forced expiratory volume in 1 s (FEV1)
      to zero. Mean rate of decline of FEV1 (percent predicted) was about 2% predicted
      per year. Variability decreases with increasing time of observation. For a 1-y
      study, with alpha = 0.05 and beta = 0.20, over 550 patients must complete the
      study in each group to show that a treatment halts pulmonary decline. For a 2-y
      study, 86 subjects in each group are required, and for 4 y, 65. Increasing the
      number of data points used to determine the rate of decline of FEV1 had only
      small effect on sample size. Use of pulmonary function data collected at regular
      intervals for research purposes did not alter these conclusions. Higher initial
      FEV1 was associated with a greater rate of decline, and among patients with
      initial FEV1 > 60% predicted, younger subjects had a faster decline than did
      older subjects. Thus, fewer subjects will be required to detect a complete halt
      in progression of lung disease if the patients are young and have mild pulmonary
      disease.

PMID- 9029633
TI  - Actin depolymerization is developmentally regulated in rat type II cells exposed
      to terbutaline.
AB  - The type II alveolar epithelial cell synthesizes and secretes pulmonary
      surfactant. Terbutaline enhances phospholipid release from adult and fetal type
      II cells. Our hypothesis is that the actin network of microfilaments regulates
      the secretory activity of the type II cell. To examine the developmental
      regulation of the changes in actin subfractions associated with secretory
      activity, cultures of type II cells derived from adult and 19-d fetal rat lung
      were incubated with or without 10 microM terbutaline for 1, 30, and 60 min. Dose
      response effects of terbutaline were examined in adult type II cells. Effects of
      phorbol ester were also examined Globular (G-actin) and filamentous (F-actin)
      fractions were extracted from the cells and analyzed separately. Specified
      cellular equivalent volumes of each subfraction were analyzed by Western
      blotting, visualized by a color reaction, and quantified by densitometry. There
      was a decrease in the cytoskeletal F-actin pool along with an increase in the G
      actin fraction within I min in adult type II cells exposed to terbutaline,
      indicating that depolymerization of F-actin occurs. Values returned to control
      levels by 60 min. In contrast, the decrease in F-actin, with a concomitant
      increase in G-actin, was maximal at 60 min in fetal cells exposed to terbutaline.
      There was a dose-dependent increase in actin depolymerization with maximal
      effects at 10 microM terbutaline. Phorbol ester also caused an increase in actin
      depolymerization. Depolymerization of the actin microfilament network may
      regulate transport and exocytosis of lamellar bodies in type II cells. We
      speculate that there is an early secretory mechanism that involves
      depolymerization of actin microfilaments and a late, actin-independent secretory
      mechanism present in adult type II cells. The timing of the response of the actin
      dependent pathway is developmentally regulated. This may explain the
      developmental differences in the secretion of surfactant that we have previously
      shown.

PMID- 9029635
TI  - Simultaneous measurement of the rates of appearance of palmitic and linoleic acid
      in critically ill infants.
AB  - Lipolysis has been measured in humans by means of stable isotope techniques using
      labeled palmitic acid (PA) or glycerol as tracers. If other fatty acids (FA) such
      as linoleic acid (LLA) have the same rate of appearance (Ra) as PA and therefore
      contribute equally to oxidative and nonoxidative metabolism is unknown. We
      infused albumin-bound [U-13C]PA and [U-13C]LLA in seven critically ill infants
      (weight 3.6 +/- 1.3 kg, age 57 +/- 64 d) receiving 20.9 +/- 5.4 kcal. kg-1.d-1 of
      i.v. glucose only, and measured simultaneously the Ra of PA and LLA from the
      isotopic enrichment of plasma FFA by mass spectrometry. A needle biopsy of the
      s.c. adipose tissue was obtained for FA composition. PA in adipose tissue was
      higher than LLA (40 +/- 6.7 versus 5.4 +/- 3.2 mol %, p < 0.001). The Ra values
      of PA and LLA were 5.73 +/- 2.79 and 1.34 +/- 0.92 mumol.kg-1.min-1, respectively
      (p = 0.005). However, the ratio of the FA's Ra to their respective mol% values in
      adipose tissue was lower for PA than for LLA (0.15 +/- 0.06 versus 0.25 +/- 0.06,
      p = 0.02). The Ra of LLA acid was higher than could be expected from the FA
      composition of adipose tissue, thus indicating a preferential release of LLA
      during lipolysis. In critically ill infants receiving only i.v. glucose, the
      contribution of LLA to the oxidative and nonoxidative metabolism may be larger
      than what assumed from the FA composition of plasma and adipose tissue.

PMID- 9029634
TI  - Partial liquid ventilation combined with inhaled nitric oxide in acute
      respiratory failure with pulmonary hypertension in piglets.
AB  - This study was a prospective, randomized, controlled design to evaluate gas
      exchange, lung mechanics, and pulmonary hemodynamics during partial liquid
      ventilation (PLV) combined with inhaled nitric oxide (NO) in acute respiratory
      failure (ARF) with pulmonary hypertension (PH). ARF with PH was induced in 12
      piglets weighing 9.7-13.7 kg by repeated lung lavages and the continuous infusion
      of the stable endoperoxane analog of thromboxane. Thereafter the animals were
      randomly assigned either for PLV or conventional mechanical ventilation (CMV) at
      a fractional concentration of inspired O2 (Fio2) of 1.0. Perfluorocarbon (PFC)
      liquid (30 mL kg-1) was instilled into the endotracheal tube over 5 min followed
      by 5 mL kg-1h-1. All animals were treated with different concentrations of NO (1
      10-20 ppm) inhaled in random order. Continuous monitoring included ECG, right
      atrial (Pra), mean pulmonary artery (Ppa), pulmonary capillary (Ppc'), and mean
      arterial (Pa) pressures, arteria oxygen saturation, and mixed venous oxygen
      saturation measurements. During PLV Pao2/Fio2 increased significantly from 8.2 +/
      0.4 kPa to 34.8 +/- 5.1 kPa (p < 0.01), whereas Pao2/FiO2 remained constant at
      9.5 +/- 0.4 kPa during CMV. The infusion of the endoperoxane analog resulted in a
      sudden decrease of Pao2/Fio2 from 34.8 +/- 5.1 kPa to 14.1 +/- 0.4 kPa (p < 0.01)
      in the PLV group and from 9.5 +/- 0.4 kPa to 6.9 +/- 0.2 kPa (p < 0.05) in the
      control group. Inhaled NO significantly improved oxygenation in both groups
      (Pao2/Fio2: 45.7 +/- 5.3 kPa during PLV and 25.9 +/- 4.7 kPa during CMV). During
      inhalation of NO mean Ppa decreased significantly from 7.8 +/- 0.26 kPa to 4.2 +/
      0.26 kPa (p < 0.01) in the PLV group and from 7.4 +/- 0.26 kPa to 5.1 +/- 0.13
      kPa (p < 0.01) in the control group. As documented in the literature PLV
      significantly improves oxygenation and lung mechanics in severe ARF. In addition,
      when ARF is associated with severe PH, the combined treatment of PLV and inhaled
      NO improves pulmonary hemodynamics resulting in better oxygenation.

PMID- 9029636
TI  - Intermediates in endogenous synthesis of C22:6 omega 3 and C20:4 omega 6 by term
      and preterm infants.
AB  - An alternative pathway of omega 3 and omega 6 fatty acid metabolism has been
      described in isolated rate hepatocytes and human fibroblasts. This alternative
      pathway, which is independent of delta 4 desaturation, involves elongation of C22
      5 omega 3 and C22:4 omega 6 to C24 fatty acids, delta 6 desaturation of the C24
      fatty acids and subsequent beta oxidation of the desaturated products to C22:6
      omega 3 and C22:5 omega 6. To determine whether this alternative pathway is
      operative in the human infant and also to obtain additional information
      concerning endogenous conversion of C18:3 omega 3 and C18:2 omega 6 to longer
      chain more unsaturated fatty acids, presence of [M + 18] isotopomers of omega 3
      and omega 6 fatty acids in the plasma phospholipid fraction of term and preterm
      infants after administration of [U-13C]18:3 omega 3 and [U-13C]18:2 omega 6 was
      determined by negative chemical ionization gas chromatography/mass spectrometry.
      [M + 18] isotopomers of the following omega 3 fatty acids were detected: C18:3,
      C18:4, C20:3, C20:4, C20:5, C22:4, C22:5, C22:6, C24:4 (two infants only), C24:5,
      and C24:6. [M + 18] isotopomers of omega 6 fatty acids detected included only
      C18:2, C18:3, C20:2, C20:3, and C20:4, but sensitivity was insufficient to detect
      [M + 18] isotopomers of C22 and C24 omega 6 fatty acids. Presence of [M + 18]
      isotopomers of C24:5 omega 3 and C24:6 omega 3 indicates that these fatty acids
      were synthesized endogenously from C18:3 omega 3. This plus the in vitro data
      strongly suggests that infants use the recently described alternative pathway in
      endogenous synthesis of C22:6 omega 3. However, involvement also of delta 4
      desaturation cannot be excluded. Detection of [M + 18] isotopomers of C20:3 omega
      3, C20:2 omega 6, and C22:4 omega 3 suggests that C18:3 omega 3, C18:2 omega 6,
      and C20:4 omega 3 are elongated as well as desaturated. The specific fate of
      these elongation products and their importance in endogenous synthesis of omega 3
      and omega 6 long chain polyunsaturated fatty acids remain to be determined.

PMID- 9029637
TI  - Mothers' milk enhances the acceptance of cereal during weaning.
AB  - Although baby food manufacturers and child care manuals often advise parents to
      prepare their infant's cereal with water or either mother's milk or formula,
      depending on the feeding regimen of the infant, little is known about the
      infant's acceptance of differently flavored cereals. The present study
      demonstrates that breast-fed infants, who had been fed cereal for approximately 2
      wk but had experienced cereal prepared only with water, consumed more of the
      cereal-mother's milk mixture compared with cereal water mixture and displayed a
      series of behaviors signaling their preferences for the former. Moreover, the
      infants' willingness to accept the flavored cereal is correlated with their
      mothers' reported willingness to try novel foods and flavors.

PMID- 9029638
TI  - Hypoparathyroidism and deafness associated with pleioplasmic large scale
      rearrangements of the mitochondrial DNA: a clinical and molecular genetic study
      of four children with Kearns-Sayre syndrome.
AB  - In four children with hypoparathyroidism and deafness as initial major
      manifestations of Kearns-Sayre syndrome, a unique pattern of mitochondrial DNA
      rearrangements was observed. Hypocalcemic tetany caused by PTH deficiency started
      between age of 6-13 y and was well controlled by small amounts of 1.25-(OH)2
      cholecalciferol. Rearranged mitochondrial genomes were present in blood cells of
      all patients and consisted of partially duplicated and deleted molecules, created
      by the loss of 7813, 8348, 8587, and 9485 bp, respectively. The deletions were
      localized between the origins of replication of heavy and light strands and
      encompassed at least eight polypeptide-encoding genes and six tRNA genes.
      Sequence analysis revealed imperfect direct repeats present in all rearrangements
      flanking the break-points. The duplicated population accounted for 25-53% of the
      mitochondrial genome and was predominant to the deleted DNA (5-30%) in all cases.
      The proportions of the mutant populations (30-75%) correlated with the age at
      onset of the disease. We conclude that, unlike heteroplasmic deletions,
      pleioplasmic rearrangements may escape selection in rapid-dividing cells,
      distribute widely over many tissues, and thus cause multisystem involvement.
      Hypoparathyroidism and deafness might be the result of altered signaling pathway
      caused by selective ATP deficiency.

PMID- 9029640
TI  - A deletion in the long arm of chromosome 18 in a child with serum carnosinase
      deficiency.
AB  - The dipeptides carnosine and anserine, found exclusively in meats, are hydrolyzed
      in serum by the enzyme carnosinase. Several reports of serum carnosinase
      deficiency describe a variable phenotype, which ranges from normal to severe
      psychomotor retardation, hypotonia, and myoclonic seizures in the first year of
      life. We report the case of a 30-mo-old girl with hypotonia, developmental
      delays, and tremor. Although consuming nominal quantities of meal, she excreted
      large amounts of carnosine and anserine. A strict meat-free diet ameliorated, but
      did not eliminate, these abnormalities. Serum carnosinase activity was found to
      be extremely low. Analysis of this child's chromosomes revealed a terminal
      deletion of chromosome 18 with breakpoint at q21.3. Neither parent exhibited this
      deletion, suggesting it was generated de novo in the patient or in a parental
      germ cell. Molecular studies showed that the patient's paternal chromosome 18 was
      deleted. Urinary carnosine excretion and serum carnosinase activity were normal
      in the patient's father. The mother had low carnosinase activity. The patient's
      brother exhibited moderate hypercarnosinuria and intermediate enzyme activity,
      consistent with the carrier state for carnosinase deficiency. Cumulatively, these
      findings suggest that the locus for this enzyme resides on the distal long arm of
      chromosome 18, and they are consistent with an unusual mechanism for the
      inheritance of this, typically autosomal recessive, condition. We conclude that
      this patient is likely hemizygous for the defect, having received the deficiency
      allele from her mother and, by virtue of the chromosomal deletion, no allele from
      her father. This represents the first report of a chromosomal abnormality in
      association with serum carnosinase deficiency and should aid in further
      localization of the gene encoding serum carnosinase.

PMID- 9029639
TI  - A survey of the newborn populations in Belgium, Germany, Poland, Czech Republic,
      Hungary, Bulgaria, Spain, Turkey, and Japan for the G985 variant allele with
      haplotype analysis at the medium chain Acyl-CoA dehydrogenase gene locus:
      clinical and evolutionary consideration.
AB  - Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty
      acid metabolism. It is one of the most frequent genetic metabolic disorders among
      Caucasian children. The G985 allele represented 90% of all the variant alleles of
      the MCAD gene in an extensive series of retrospective studies. To study the
      distribution of the G985 allele, newborn blood samples from the following
      countries were tested; 3000 from Germany (1/116). 1000 each from Belgium (1/77).
      Poland (1/98), Czech Republic (1/240). Hungary (1/168), Bulgaria (1/91), Spain
      (1/141). Turkey (1/216), and 500 from Japan (none). The frequency is shown in
      parentheses. The haplotype of G985 alleles in 1 homozygote and 57 heterozygote
      samples were then analyzed using two intragenic MCAD gene polymorphisms (Iaq1 and
      GT-repeat). The result indicated that only 1 of the 10 known haplotypes was
      associated with the G985 mutation, suggesting that G985 was derived originally
      from a single ancestral source. We made a compilation of the G985 frequencies in
      these countries and those in nine other European countries studied previously.
      The G985 distribution was high in the area stretching from Russia to Bulgaria in
      the east and in all northern countries in western and middle Europe, but low in
      the southern part of western and middle Europe. The incidence among ethnic
      Basques appeared to be low. This distribution pattern and the fact that all G985
      alleles belong to a single haplotype suggest that G985 mutation occurred later
      than the delta F508 mutation of the CFTR, possibly in the neolithic or in a later
      period, and was brought into Europe by IndoEuropean-speaking people. The
      panEuropean distribution of the G985 allele, including Slavic countries from
      which patients with MCAD deficiency have rarely been detected, indicates the
      importance of raising the level of awareness of this disease.

PMID- 9029641
TI  - Association of -158 (C-->T) (XmnI) DNA polymorphism in G gamma-globin promoter
      with delayed switchover from fetal to adult hemoglobin synthesis.
AB  - In this study, the effect of -158 (C-->T) (XmnI) polymorphism on the synthesis of
      fetal Hb and its G gamma component during the switchover from fetal to adult Hb
      was examined using cord blood samples from normal Caucasian term infants. The
      presence of -158(C-->T) mutation was determined by amplification of G gamma and A
      gamma-globin gene promoter fragments from the DNA isolated from cord blood
      samples, followed by XmnI restriction enzyme digestion. The syntheses of fetal
      and adult Hb in cord blood were measured by [3H]leucine incorporation in globin
      synthesis, separation of the globin polypeptides by HPLC, and scintillation
      counting of the fractions. The presence of -158(C-->T) substitution in the G
      gamma-globin promoter region was positively correlated with elevated synthesis of
      fetal Hb and its G gamma-globin component in term newborn infants and is
      associated with delayed switchover from fetal to adult Hb. In addition analysis
      of cord blood samples from 100 normal Caucasian French Canadian term infants
      revealed that the frequency of -158(C-->T) substitution in G gamma-promoter was
      0.32.

PMID- 9029642
TI  - Deficient thromboxane synthesis and response in platelets from premature infants.
AB  - In vitro function of cord blood platelets from 35 premature infants (gestational
      age 32 +/- 3.2 wk) was compared with that of 12 full-term infants and 14 adult
      control subjects. In comparison with adult platelets, preterm platelets showed
      impaired aggregation, in response to thrombin, collagen, ADP, and U46619 [a
      stable analog of thromboxane A2 (TxA2)], and impaired [14C]serotonin secretion in
      response to collagen and U46619. The production of TxB2 (the stable TxA2
      metabolite) in response to collagen was reduced in preterm platelets (30.2 +/-
      5.5 ng/mL) compared with full-term (52.7 +/- 12.6 ng/mL) or adult control
      platelets (132.3 +/- 38.7 ng/mL). The deficient TxB2 production and U46619
      response prompted further investigation of TxA2 receptor number and binding
      characteristics. Immunoblotting using an anti-TxA2 receptor antibody (anti-P2)
      identified a single, identical 55-kD band in solubilized membranes of control,
      full-term, and preterm platelets. Flow cytometry using anti-P2 produced
      histograms that did not differ between adults and neonates. Ligand binding
      studies using [3H]U46619 were carried out on 10 samples from each group.
      Scatchard analysis yielded a single class of binding sites with no significant
      difference among the Kd values (85 +/- 16 versus 99 +/- 12 versus 100 +/- 12 nM)
      or number of binding sites per platelet (1876 +/- 460 versus 2450 +/- 478 versus
      2777 +/- 536) for preterm and full-term infants and adults. Therefore platelets
      of preterm infants show impaired TxA2 production and response. The poor response
      is not related to altered binding characteristics of the TxA2 receptor but may
      lie in the postreceptor signal transduction pathway.

PMID- 9029643
TI  - Body iron stores decrease in boys during pubertal development: the transferrin
      receptor-ferritin ratio as an indicator of iron status.
AB  - The transferrin receptor in serum provides a useful measure of tissue iron
      deficiency and the rate of erythropoiesis, whereas serum ferritin reflects the
      amount of storage iron in normal subjects. We studied the serum transferrin
      receptor and the transferrin receptor-ferritin ratio in 57 healthy prepubertal or
      early pubertal boys and followed them at 3-mo intervals for 24 mo to evaluate
      their iron status during puberty. The mean laboratory parameters changed as
      follows: Hb from 13.0 to 13.3 g/dL (p = 0.01), mean corpuscular volume from 85 to
      84 fL (p = 0.0001), transferrin receptor from 6900 to 7200 micrograms/L (p =
      0.03) ferritin from 36 to 23 micrograms/L (p = 0.0001), and transferrin receptor
      ferritin ratio from 230 to 400 (p = 0.0001). At the start of the investigation,
      the serum transferrin receptor was elevated (> 9000 micrograms/l) or ferritin low
      (< = or 12 micrograms/L) in fewer than 2% of the boys. During the subsequent 2 y
      the proportion of boys with an elevated transferrin receptor or low ferritin
      value increased. The two parameters were simultaneously abnormal in none of the
      boys initially, but in about 3% of the boys 2 y later. The change in transferrin
      receptor-ferritin ratio was closely correlated with genital development. The
      proportion of elevated transferrin receptor-ferritin ratios increased 4.5-fold
      during the 2 y, indicating the high responsiveness of the ratio. At the end of
      the study, iron therapy was started to eliminate any iron deficiency. In response
      to the therapy, the mean transferrin receptor-ferritin ratio fell to 210 +/- 19,
      i.e. close to the level at the beginning of the study. The marked responses of
      the transferrin receptor and the receptor-ferritin ratio to iron therapy reflect
      the dependence of these parameters on iron status rather than on physiologic
      differences in the rate of erythropoiesis.

PMID- 9029644
TI  - Lack of evidence for rotavirus by polymerase chain reaction/enzyme immunoassay of
      hepatobiliary samples from children with biliary atresia.
AB  - The purpose of this study was to analyze hepatobiliary samples of patients with
      biliary atresia for rotavirus groups. A, B, and C, because group A rotavirus had
      been used to produce an animal model of the disease and group C rotavirus had
      been found in hepatobiliary samples from one group of patients. Biliary remnants
      and liver tissue from 10 biliary atresia and 14 control patients with other liver
      diseases were examined for rotavirus groups A, B, and C using nonisotopic,
      reverse transcriptase polymerase chain reaction enzyme immunoassay. Biliary
      atresia patients had a median age of 3 mo and were from a confined geographic
      area. Rotaviral stocks from groups A and C were used as polymerase chain reaction
      positive controls. The limits of detection for rotaviral RNA from these two
      groups were respectively, 5 plaque-forming units and 50 tissue culture infectious
      doses (ID50). Tissue culture was 100-fold less sensitive for groups A and C than
      the polymerase chain reaction. The nested nonisotopic probes hybridized in
      solution only with their homologous target DNAs as determined by the enzyme
      immunoassay, or by Southern blot hybridization. Although it was possible to
      detect mRNA from a beta-actin housekeeping gene in all of the hepatobiliary
      samples, no evidence of rotaviral RNA was found in either the biliary atresia or
      the negative control group. In conclusion, rotavirus is not a common viral
      etiology of biliary atresia.

PMID- 9029645
TI  - Increased activity of lysosomal acid hydrolases in the cell-free cerebrospinal
      fluid of bacterial meningitis.
AB  - Because inflammation could affect lysosomal enzyme trafficking, resulting in
      increased enzyme release from the cells, tissue necrosis, or altered blood- and
      the brain-cerebrospinal fluid (CSF) barrier, the activity of four lysosomal
      enzymes in the cell-free CSF of 34 patients with bacterial meningitis, 20 with
      aseptic meningitis, and 39 control subjects was measured. Activities are
      expressed in nanomoles of 4-methylumbelliferone mL/h. The median beta
      hexosaminidase A activity in bacterial meningitis was 313, in aseptic meningitis
      it was 173, and in the control subjects it was 175, the median beta
      hexosaminidase B activity was 417, 165, and 120; the median alpha-mannosidase
      activity was 171, 124, and 113; and the median beta-glucuronidase activity was
      133.7, 14.3, and 10.0, respectively. The difference of the activities of the four
      enzymes measured between the bacteria meningitis and the controls is significant
      (p < 0.000). Also significant is the difference between bacterial and aseptic
      meningitis (p = 0.005 to < 0.000), but it is not significant between aseptic and
      control subjects. Both the sensitivity and specificity of the beta-glucuronidase
      activity between bacterial meningitis and control subjects were 100%, whereas the
      corresponding values between bacterial and aseptic meningitis were 100% and 90%,
      respectively. No significant correlation was observed between the activities of
      the enzymes measured and the number of the polymorphonuclear leukocytes or other
      laboratory characteristics of the CSF. The increased lysosomal enzyme activities
      in the CSF of patients with meningitis may result from diffusion across the blood
      CSF or the brain-CSF barrier or from enzyme leakage through the cell membranes.

PMID- 9029646
TI  - Metabolic alterations in the fetal hepatic and umbilical circulations during
      glucocorticoid-induced parturition in sheep.
AB  - Fetal hepatic amino acid metabolism has unique features in comparison to
      postnatal life. Thus, it seemed likely that this metabolism might be changed by
      the endocrine changes which precede birth. To explore the changes in placental
      and fetal carbohydrate and amino acid metabolism that occur during parturition,
      labor was induced in six ewes at 131 +/- 1 d gestation with a fetal infusion of
      dexamethasone. For purpose of chemical analysis, blood was withdrawn before and
      approximately 3 and 25 h from the start of the infusion from maternal arterial,
      uterine venous, umbilical venous, fetal arterial, and left hepatic venous
      catheters. Fetal oxygenation remained normal. At 25 h, both fetal and maternal
      arterial plasma glucose concentrations increased (p < 0.01 and p < 0.02,
      respectively) and umbilical glucose uptake decreased (p < 0.05). Fetal glutamate
      showed a significant reduction in its hepatic output (p < 0.05) with a
      concomitant reduction in fetal arterial plasma concentration (p < 0.05) and
      placental uptake (p < 0.01). Fetal plasma concentrations of several other amino
      acids were markedly increased. The reduction in placental glutamate uptake was
      temporally associated with a decline in progesterone release by the pregnant
      uterus. These data suggest the hypothesis that glutamate plays a role in
      integrating the complex changes in placental and fetal hepatic metabolism that
      occur during parturition.

PMID- 9029647
TI  - Growth hormone release induced by growth hormone-releasing hexapeptide is not
      mediated by thyrotropin-releasing hormone in neonatal rats.
AB  - GH-releasing hexapeptide (GHRP-6) and nursing stimulate GH secretion in rat pups
      via GH-releasing factors (GRFs: distinct from GH-releasing hormone (GHRH). It was
      determined whether GH secretion induced by GHRP-6 or nursing was mediated by TSH
      releasing hormone (TRH) in 2-d-old rats. In vitro. GHRP-6 and TRH stimulated GH
      secretion of neonatal pituitary glands. At their maximally effective doses, GHRP
      6 and TRH evoked approximately equal GH responses. Treatment with a combination
      of the maximally effective doses of GHRP-6 and TRH resulted in a GH response
      comparable to that evoked by either treatment alone. GHRP-6 in vivo induced a
      greater GH response than did TRH. Treatment in vivo with a combination of the
      maximally effective doses of GHRP-6 and TRH synergistically increased serum GH
      levels. Unlike GHRP-6 TRH was an effective stimulus of prolactin secretion either
      in vitro or in vivo. Nursing was an effective stimulus for GH secretion, but only
      marginally increased serum prolactin levels. The effects of either of the
      peptides and nursing on GH secretion were additive. These results suggest that
      GHRP-6 stimulates GH secretion both by acting directly on the pituitary gland and
      indirectly via a hypothalamic GRF. The indirect effect appears to be greater. The
      alternative GRFs released by GHRP-6 or nursing are distinct from each other and
      from TRH. These findings suggest that alternative GRFs play a significant role in
      the regulation of GH secretion in neonatal rats.

PMID- 9029648
TI  - Spatial polarization of insulin-like growth factor receptors on the human
      syncytiotrophoblast.
AB  - The expression of IGF receptors on the maternal-facing, microvillous membrane
      (MVM) surface and the fetal-facing, basal membrane (BM) surface of the
      syncytiotrophoblast was studied using standard ligand binding assays, covalent
      cross-linking techniques, and immunoblot analysis. Scatchard analysis of
      [125I]IGF-I and -II binding revealed the presence of both high and low affinity
      binding sites associated with each membrane preparation that did not clearly
      distinguish between the two membrane preparations. Cross-linking analysis,
      however, demonstrated type I and type II IGF receptors associated primarily with
      MVM, suggesting that nonreceptor binding sites may contribute to total membrane
      binding. Ligand blot analysis revealed that BM are uniquely associated with 29-
      and 24-kD IGF binding proteins (IGFBPs). [125I]QAYL-IGF-I, having reduced
      affinity for IGFBPs, was therefore used to study receptor-specific binding.
      Approximately 5-fold more type I IGF receptors were shown to be associated with
      MVM than BM by Scatchard and cross-linking analyses. This was confirmed by
      immunoblot analysis. By contrast, immunoblot analysis revealed approximately 50
      100% more type II IGF receptor protein associated with BM, whereas cross-linking
      to [125I]IGF-II revealed a MVM predominance. In the presence of 5 mM mannose 6
      phosphate, however, a substantial increase in [125I]IGF-II cross-linked to the
      type II IGF receptor was observed in BM but not MVM consistent with immunoblot
      analysis. These data demonstrate that type 1 and unoccupied type II IGF receptors
      are expressed primarily on the maternal-facing. MVM surface of the
      syncytiotrophoblast.

PMID- 9029649
TI  - Biochemical selection of prepubertal patients with androgen insensitivity
      syndrome by sex hormone-binding globulin response to the human chorionic
      gonadotropin test.
AB  - Before puberty, the diagnosis of androgen insensitivity syndrome (AIS) can be
      difficult. We studied whether the decrease of sex hormone-binding globulin (SHBG)
      during the human chorionic gonadotropin (hCG) test may represent a biochemical
      test to select prepubertal patients with AIS. We examined prepubertal patients
      with AIS (n = 9, age 0.9-8.2 y), male pseudohermaphroditism not due to AIS (other
      MPH) (n = 8, age 0.6-10.7 y), and control boys (n = 12, age 0.8-12.5 y).
      Testosterone and SHBG levels (mean +/- SD) were measured before (d 0) and after
      (d 5) a hCG test (1500 IU X 3 d). Testosterone levels (nmol/L) increased in all
      groups [AIS: from 1.5 +/- 1.2 to 22.1 +/- 11.8 (p < 0.001); other-MPH: from 0.6
      +/- 0.6 to 9.2 +/- 7.4 (p < 0.02); controls: from 1.8 +/- 1.4 to 22.8 +/- 14.4 (p
      < 0.001)]. SHBG concentrations (nmol/L) did not change in AIS [from 66.2 +/- 15.1
      to 67.5 +/- 18.6 (p = NS), delta-variation 1.7 +/- 12.7%], whereas they were
      significantly decreased in other-MPH [from 59.9 +/- 14.2 to 46.5 +/- 18.6 (p <
      0.005), delta-variation -23.7 +/- 19.6%] and controls [from 63.0 +/- 16.9 to 33.7
      +/- 14.6 (p < 0.003), delta-variation -46.9 +/- 15.2%]. Our data suggest that the
      SHBG changes during the hCG test can be used to assess in vivo the biologic
      response to androgens in prepubertal patients with ambiguous genitalia, selecting
      those patients in whom it is worth performing second level investigations to
      confirm the AIS diagnosis.

PMID- 9029650
TI  - Change in blood pressure during pubertal insulin resistance.
AB  - To examine the levels and relationship of blood pressure and insulin during
      puberty, blood pressure and serum insulin were measured in 3596 subjects, aged 3
      18 y, whose pubertal status was graded according to the Tanner classification.
      The same study protocol was repeated in two follow-up surveys 3 and 6 y later for
      2991 6-21-y-old subjects and 2799 9-24-y-old subjects, respectively. There was a
      37-66% increase in insulin at Tanner stage 3 (pubic hair) among the female
      subjects and at Tanner stage 5 (pubic hair) among the male subjects, after which
      insulin started to decrease. The mean systolic and diastolic blood pressure
      increased steadily throughout puberty. The rise in blood pressure continued
      during early adulthood, despite the decrease in serum insulin. The correlation
      between systolic blood pressure and insulin measured in the same year was weak at
      each pubertal stage after standardization for weight, except among the female
      subjects at mid puberty. There was no relation between diastolic blood pressure
      and insulin. Adult systolic blood pressure could be predicted by pubertal insulin
      among the male subjects after adjustment for age and weight (partial correlation
      coefficient 0.21), but among the female subjects this relation was trivial
      (partial correlation coefficient 0.08). We conclude that the correlation between
      insulin and actual blood pressure vanishes during puberty, whereas pubertal
      insulin and future adult male systolic blood pressure seem to correlate.

PMID- 9029651
TI  - Spectral pattern of neonatal cerebral blood flow velocity: comparison with
      spectra from blood pressure and heart rate.
AB  - The cerebral blood flow velocity (CBFV) frequency spectra were studied in 106
      premature and term newborns (gestational age range. 24-42 wk) and compared with
      the heart rate (HR) and mean arterial blood pressure (BP) spectra over the 0.005
      0.5 Hz range. CBFV, BP, and HR were shown to have similar but not identical
      spectral patterns. Adjustment of a l/f model to these spectra produced highly
      significant fittings, but the residuals were not independent. This condition was
      met only by the CBFV and BP spectra over a limited frequency range (0.005-0.06
      Hz). These results provide a characterization of the CBFV spectra for a much
      larger population of newborns than hitherto available, indicating that under
      certain conditions CBFV and BP might show the properties of chaotic systems. In
      infants without major complications, gestational age (GA) did not have a
      significant influence on the CBFV spectrum, whereas the spectral power to 0.5 Hz
      of both BP and HR was found to increase with GA. The spectral power increased
      over the first 24 h of postnatal life for all three variables: only CBFV showed a
      significant spectral change in the low frequency (LF, 0.02-0.08 Hz) range. A
      matched group comparison, adjusted for GA and postnatal age, indicated a
      reduction in CBFV LF power for term infants with birth asphyxia when compared
      with normal infants, which was not reproduced in the HR spectra.

PMID- 9029652
TI  - Muscle isoactin expression during in vitro differentiation of murine embryonic
      stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cells derived from mouse blastocysts.
      ES cells can differentiate into complex embryoid bodies (EBs) which exhibit many
      of the characteristics of 4-10-d embryos, including areas which rhythmically
      contract. The expression of the four muscle isoactins was examined in EBs by
      using transcript-specific probes for each of the muscle actin mRNAs and
      selectively reactive MAbs to muscle actins. Northern blot analyses from
      undifferentiated ES cells and EBs after 5, 10, 15, and 20 d in suspension culture
      demonstrated that no muscle actin transcripts could be detected in the
      undifferentiated cells, whereas during differentiation, the vascular and enteric
      smooth muscle isoactin mRNAs were easily detected. To further define the pattern
      of expression polymerase chain reaction analyses were carried out on RNA isolated
      from individual EBs. The data indicated that all four muscle-specific actin genes
      are transcribed. We also demonstrated the presence of muscle actins in at least
      two distinct cell populations within the EBs using selectively reactive MAbs.
      Fibroblast-like cells exhibit significant levels of the two smooth muscle actins
      (vascular and enteric) localized to stress fibers. In addition, one or both of
      the striated muscle actins (cardiac and skeletal) are expressed in cardiomyocyte
      like cells. As is the case in embryonic heart, alpha-smooth muscle actin and the
      striated muscle actin(s) are incorporated into well organized sarcomeres in these
      cardiomyocyte-like cells. Thus, differentiating EBs provide an in vitro system to
      study both striated and smooth muscle cell gene expression.

PMID- 9029653
TI  - Acceleration of barrier ontogenesis in vitro through air exposure.
AB  - Immaturity of the epidermal barrier in the preterm infant may have serious
      clinical consequences. However, regardless of the degree of prematurity, the
      barrier rapidly matures such that by 2 wk all infants display a competent
      barrier. To determine whether the change from an aqueous (intrauterine) to a
      xeric environment might be the stimulus for this accelerated maturation, we
      examined the effects of air exposure on cutaneous barrier formation in vitro.
      Skin explants from d 17 fetal rats were incubated either submerged or at the air
      medium interface. As previously reported, a competent barrier formed under
      submerged conditions after 3-4 d, precisely mirroring the time course of
      maturation in utero. In contrast, barrier maturation was accelerated in air
      exposed explants, with functional, histologic, and structural markers of barrier
      formation observed after only 2 d of incubation. A water-impermeable membrane
      blocked the acceleration of barrier formation, resulting in a developmental time
      course comparable to that for submerged explants. In contrast a water vapor
      permeable membrane did not block the acceleration. Glucocorticoids and thyroid
      hormone, which accelerate barrier formation in utero or in vitro under submerged
      conditions, did not further accelerate barrier formation in the air-exposed
      model. These data indicate that: 1) air exposure accelerates barrier ontogenesis,
      suggesting that water flux may be an important signal for the accelerated barrier
      formation that occurs in premature infants; and 2) factors which accelerate
      barrier formation in utero may not further accelerate barrier formation in
      neonates.

PMID- 9029654
TI  - "With a little help from my friends I get by": self-help books and psychotherapy.
      Essay review.
AB  - A Bosnian mental health professional told the following story: Her village had
      been under siege for months, and she had worked around the clock in her community
      using all her personal and professional resources. She was offered a few days
      break in Zagreb and went to the city; she welcomed the chance to be out from
      under fire and to rest. A bookstore was the first place she wanted to go, to
      browse, to expand her vision, to read about other places and peoples. In the
      shop, the shelves were lined with American best-selling self-help books with
      titles like "Getting rid of the shoulds in your life in 24 hours," "How to stop
      being angry and guilty in 12 steps," etc. She looked at these and felt so unreal
      that she fled back to her village, preferring the reality of her people and her
      problems.

PMID- 9029655
TI  - Psychodynamic theory and practice in the study of political life: a review essay.
AB  - Autonomy, individuality, and freedom are values central to psychoanalytic
      inquiry. The theory, in its political form, defends the individual against the
      demands and tyrannical pressures of the group. In its applied dimension,
      psychoanalytic theory contributes considerable insight to understanding political
      relationships and the values supportive of political liberalism.

PMID- 9029656
TI  - The history of psychiatry: an opportunity for self-reflection and
      interdisciplinary dialogue. Essay review.
AB  - "Can you recommend a good one volume history of psychiatry?" I am often asked
      this question, being a psychiatric and psychoanalytic clinician who has also been
      deeply involved in the history of psychiatry, as a writer and as a teacher.
      "Single authored or multiple authored?" I ask in return and explain that if
      single authored the answer is no; if multiple authored I respond, "You have to
      await the publication of the huge encyclopedic volume(s), edited by John Gach and
      Edwin Wallace, sometime in the next few years. That 'definitive' work will not be
      definitive for very long; neither will it be inexpensive nor light reading,
      either in heft or in style." "What about Zilboorg's History of Medical
      Psychology?-I remember it as readable, portable, and quotable," my student or
      colleague continues. To that I reply, "Definitely worth reading, but you will
      have to do a lot of other reading to fill in the important omissions, to correct
      the errors of fact and interpretation, and to understand the author's
      unquestioned assumptions and biases." "Erwin Ackernecht's Short History of
      Psychiatry?" "Good book, amazing what's packed into it, but it really is short.
      If you read German very well, there is Der Wahnsinn by Leibbrand and Wettley,
      which would serve you better, but that is a huge book with small print, and for
      that too you would have to do a lot of extra reading to fill in gaps and to
      understand their biases."

PMID- 9029657
TI  - New directions in the prevention and treatment of schizophrenia: a biological
      perspective.
AB  - Our current treatments for schizophrenia are, at best, palliative. With the
      exception of counseling those families with a known high risk for having
      schizophrenic offspring, no preventive measures are currently available. The not
      too distant future, however, promises to bring improvements in somatic treatments
      as well as the possible introduction of preventive measures. We are fully aware
      that current biological treatments work best when they are combined with
      psychosocial intervention, and expect that future biological treatments and
      preventions will also involve appropriate nonbiological considerations.
      Psychosocial treatments are covered elsewhere in this issue. Here we look at how
      modern genetics, pre- and perinatal factors, early and sustained intervention,
      and new medications are likely to decrease both the number of individuals with
      schizophrenia and the severity of the illness.

PMID- 9029658
TI  - Early identification and treatment of schizophrenia: conceptual and ethical
      considerations.
AB  - To identify and start treatment of schizophrenic patients at an early stage has
      been a matter of growing interest in recent years (Alanen 1994; Birchwood 1992;
      Docherty et al. 1978; Falloon 1992; Lieberman et al. 1993). However, we are not
      aware of any controlled study definitively concluding that early treatment of
      schizophrenia is favorable. Many researchers discuss the topic, for example,
      regarding outcome and prognosis (Falloon 1992) or treatment response (Alanen
      1994; Lieberman et al. 1993). In this article we take a closer look at the idea
      of early treatment of schizophrenia by analyzing the concept of early
      schizophrenia/early psychosis at an epistemological level and discuss related
      ethical problems.

PMID- 9029659
TI  - Limitations of cognitive status exams: a case-based discussion.
AB  - Despite their extensive use in psychiatric and medical settings, brief mental
      status examinations have significant limitations that are easily overlooked in
      the pressure-cooker environments within which they are commonly used. Although
      undoubtedly of value as quick screening devices, the sheer brevity of these
      instruments all but guarantees limited validity. Brief examinations perform best
      with grossly impaired cases, alerting clinicians to the fact that something is
      badly amiss in patients who are significantly confused, disoriented, aphasic, or
      otherwise severely impaired. Very poor scores are accordingly frequently useful.
      Moderate or even perfect scores, however, will frequently be misleading, because
      patients with compromised brains often obtain them (Nelson et al. 1986). One such
      case follows.

PMID- 9029660
TI  - The role of neurocognitive deficits in understanding adaptive functioning in
      severe psychiatric illness: commentary on Hawkins and Cooper.
AB  - The presentation of Ms. E. by Hawkins and Cooper provides an excellent discussion
      of the diverse ways in which clinicians and clinical researchers are currently
      conceptualizing neurocognitive deficits within severe psychiatric disorders. The
      thorough neuropsychological evaluation of this patient provided a wealth of
      information that was completely missed by the Mini-Mental State Exam (MMSE;
      Folstein et al. 1975). As Hawkins and Cooper point out, the tendency of some
      clinicians to discount the role of neuropsychological deficiency in the face of
      adequate MMSE scores and evident psychiatric symptoms is not justified by the
      relevant clinical research literature. Furthermore, recent developments in
      scientific conceptions of the role of neurocognitive deficits in the more severe
      psychiatric disorders, such as schizophrenia, schizoaffective disorder, and
      bipolar mood disorder, deserve more attention in clinical practice.

PMID- 9029661
TI  - Multifetal pregnancy reduction: psychodynamic implications.
AB  - New reproductive technologies, such as advanced infertility treatments, may have
      significant implications for women's psychological experience of pregnancy and
      motherhood. This paper examines some of the psychodynamic implications of
      multifetal pregnancy reduction, a medical procedure in which some of the fetuses
      in a multiple pregnancy are aborted while other fetuses are carried to term.
      Forty-four women who had undergone pregnancy reductions were interviewed about
      their emotional experience of this medical intervention and their subsequent
      pregnancies. A qualitative analysis of their experience was conducted from five
      psychoanalytically-informed vantage points: drive theory, ego psychology, object
      relations theory, self psychology and a developmental perspective. Women
      experienced having to abort some of their fetuses as a stressful and distressing
      life event, and a fourth of the women experienced bereavement reactions which
      impaired their functioning for at least two weeks. Conscious and unconscious
      responses to the procedure included ambivalence, guilt, and a sense of
      narcissistic injury, increasing the complexity of their attachment to the
      remaining babies. However, the achievement of the developmental goal of parenting
      healthy birth children helped most women feel that they had made the right
      decision for themselves and their families. Further research is indicated,
      including interviews before the reduction and long-term follow-up of mothers and
      surviving children.

PMID- 9029662
TI  - Monoamine metabolites in 'leftover' newborn human cerebrospinal fluid--a
      potential resource for biobehavioral research.
AB  - Although variations in monoamine neurotransmission have been implicated in a
      variety of psychopathologic outcomes in man, little is known about how monoamines
      influence or are affected by developmental processes early in childhood. In this
      study, assays for 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA),
      and 3-methoxy-4-hydroxyphenylglycol (MHPG) were obtained from leftover
      cerebrospinal fluid (CSF) of 119 human newborns. The levels of these monoamine
      metabolites were in keeping with pre-existing 'normative' data from two small
      previously published studies. The levels were largely unaffected by variations in
      the infants' physiologic condition at the time of lumbar puncture, and exhibited
      evidence for circadian rhythms. Among 32 infants (8 neurologically normal, 24
      neurologically compromised) for whom more than one CSF sample was obtained during
      the first year of life, the correlations between baseline and follow-up
      measurements for 5-HIAA and HVA were on the order of 0.75. Correlations between
      twins (four sets) were significantly higher than those between unrelated
      individuals for 5-HIAA and HVA. At 9-month follow-up, neurologically normal
      infants in the lower extreme 15% of the distribution for 5-HIAA exhibited a trend
      toward lower scores for sociability on the Colorado Childhood Temperament
      Inventory (maternal report) than their counterparts at the upper extreme of the 5
      HIAA distribution. Leftover CSF is a readily available resource for measurements
      of monoamine metabolites (and possibly other CSF constituents) in population
      based samples of human newborns.

PMID- 9029663
TI  - Faulty cortisol/serotonin interplay. Psychopathological and biological
      characterisation of a new, hypothetical depression subtype (SeCA depression)
AB  - The hypothesis is proposed of a new subtype of depression named: stressor
      precipitated, cortisol-induced, serotonin-related, anxiety/aggression-driven
      depression (SeCA depression). Biologically, these patients are characterized by
      impaired 5-HT synthesis and reduced 5-HT1A receptor sensitivity. Under normal
      conditions these functions proceed marginally; in times of stress they easily
      fail, due to sustained overproduction of cortisol. Psychopathologically this
      depression type shows the following characteristics: anxiety and aggression, not
      mood lowering, heralding a depressive episode; the personality structure shows
      'character neurotic' impairments and tolerance for (certain) traumatic life
      events is low. As specific therapeutic agents selective 5-HT1A agonists and
      cortisol or CRH antagonists are proposed. Prophylactically, maintenance treatment
      with 5-HT1A agonists seems indicated as well as psychological interventions to
      increase the stressor threshold.

PMID- 9029664
TI  - Lower total serum protein, albumin, and beta- and gamma-globulin in major and
      treatment-resistant depression: effects of antidepressant treatments.
AB  - Strong evidence has recently been reported that major depression is accompanied
      by an acute phase response (APR), characterized by elevated levels of positive
      acute phase proteins (APPs) and decreased levels of negative APPs. The APR is
      also reflected in lowered total serum protein (TSP) and specific changes in the
      major electrophoretically separated protein fractions. The present study examined
      pretreatment and posttreatment serum TSP and the concentrations and percentages
      of the major electrophoretically separated serum protein fractions in 37 major
      depressed subjects, of whom 29 had treatment-resistant depression (TRD), and in
      29 normal controls. We found that TSP and the percentage and concentration of
      serum albumin (Alb) and gamma-globulin fraction were significantly lower in major
      depression and TRD than in normal controls. Serum beta-globulin concentrations
      were significantly lower in major depressed and TRD subjects than in normal
      controls. The percentages of the alpha 1- and alpha 2-globulin fractions were
      significantly higher in major depressed subjects than in normal controls. There
      were no significant effects of subchronic treatment with antidepressants on TSP,
      the percentage or concentration of the major electrophoretically separated
      protein fractions, i.e. alpha 1-, alpha 2- and beta-globulin. There was a
      significant increase in percentage of the gamma-globulin fraction after
      subchronic treatment with antidepressants. The results support the hypothesis
      that major depression and TRD are accompanied by a chronic APR.

PMID- 9029665
TI  - Increased production of interleukin-2 (IL-2) but not soluble interleukin-2
      receptors (sIL-2R) in unmedicated patients with schizophrenia and
      schizophreniform disorder.
AB  - This study investigated immune activation, as measured by production of
      interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R) from stimulated
      lymphocytes, in schizophrenia and schizophreniform disorder. The study included
      13 neuroleptic-free patients, 13 medicated patients and 13 age- and sex-matched
      control subjects. Production of IL-2 and sIL-2R by peripheral blood mononuclear
      cells (PBMCs) was measured after in vitro stimulation with phytohaemagglutinin
      (PHA). Patients' symptoms were rated on the Scales for Assessment of Positive
      (SAPS) and Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale
      (BPRS). IL-2 production by stimulated lymphocytes was significantly elevated in
      neuroleptic-free patients compared with both medicated patients and control
      subjects. IL-2 production was inversely correlated with the SAPS subscales of
      bizarre behaviour and formal thought disorder. The pattern of increased IL-2
      production is in contrast to previous findings in patients with schizophrenia.
      Significant associations with clinical rating scores suggest that IL-2 production
      may vary in different biological subgroups of schizophrenia and schizophreniform
      disorder.

PMID- 9029666
TI  - Dopamine agonist amineptine prevents the antidepressant effect of sleep
      deprivation.
AB  - In a double-blind study, the effects of the interaction between the
      administration of amineptine versus placebo and repeated cycles of total sleep
      deprivation (TSD), which is thought to act through an enhancement in dopaminergic
      transmission, were analyzed. Twenty-two consecutively admitted patients with
      bipolar depression formed the study group. Repeated administrations of TSD
      significantly enhanced perceived mood levels in placebo-treated patients, while
      amineptine administration blocked the antidepressant action of TSD. Hypothesized
      changes in brain dopaminergic transmission attributable to amineptine
      pretreatment are discussed.

PMID- 9029667
TI  - The Tridimensional Personality Questionnaire in obsessive-compulsive disorder.
AB  - This study examined the Tridimensional Personality Questionnaire in 32 patients
      with obsessive-compulsive disorder. Scores on the Harm Avoidance (HA) dimension
      alone were found to distinguish the patient from normal volunteers. The impact of
      multiple anxiety disorders and of the specific lower-order HA trait of fear of
      uncertainty was also demonstrated.

PMID- 9029668
TI  - The Children's Affective Lability Scale: a psychometric evaluation of
      reliability.
AB  - The Children's Affective Lability Scale (CALS) is a 20-item parent report measure
      developed to assess affect regulation in children aged 6-16. It was normed with
      school children in regular education classrooms and with children hospitalized in
      a psychiatric facility. Internal-consistency reliability, split-half reliability,
      and two-week test-retest reliability were excellent. Staff interrater reliability
      in the psychiatric sample was acceptable. Higher CALS scores were observed in an
      in-patient psychiatric sample than in either an out-patient or a normative
      sample. A principal components factor analysis yielded two components for the
      normative sample.

PMID- 9029669
TI  - Renal tubular epithelial cell-E. coli interaction products stimulate nitric oxide
      production in cultured rat renal medullary interstitial and mesangial cells.
AB  - Tubulointerstitial and periglomerular inflammation and fibrosis are important
      consequences of pyelonephritis. The pathogenesis of these abnormalities is not
      fully understood. Renal tubular epithelial cells (RTEC) elaborate biologically
      active materials following incubation with bacteria. Nitric oxide (NO) is an
      inflammatory mediator and it modulates the accumulation of extracellular matrix
      proteins. Therefore, we studied whether RTEC-E. coli interaction products
      regulate NO production by cultured rat renal medullary interstitial cells (RMIC)
      and mesangial cells (MC). RMIC and MC were maintained in media containing IFN
      gamma and LPS for 24-72 h. Test media contained either no further additives or
      20% supernatants from RTEC incubated with E. coli or bacterial cell products.
      RTEC-E. coli interaction products significantly increased NO production in RMIC
      and MC. This stimulation in NO production was not associated with changes in
      inducible nitric oxide synthase (iNOS) gene or protein expression. These findings
      indicate that RTEC-E. coli interaction products increase NO production in RMIC
      and MC by directly stimulating iNOS enzymatic activity. Altered NO production by
      renal cells may contribute to tubulointerstitial inflammation in acute and
      chronic pyelonephritis.

PMID- 9029670
TI  - Impairment of endothelium-dependent relaxation of the isolated basilar artery
      from streptozotocin-induced diabetic rats.
AB  - In the isolated rat basilar artery, acetylcholine (ACh) caused concentration
      dependent relaxation. The relaxation induced by ACh was significantly inhibited
      by NG-nitro-L-arginine (L-NNA) (10(-4) M) or isotonic high K+ medium (30 mM) but
      not by treatment with indomethacin (3 x 10(-5) M) or glibenclamide (10(-6) M).
      The relaxation was abolished by the combined treatment with L-NNA and isotonic
      high K+ (30 mM). The relaxation caused by ACh was significantly attenuated in the
      basilar artery from streptozotocin (STZ)-induced diabetic rats. L-NNA caused
      contractile response in the isolated basilar artery and this response was
      significantly attenuated in diabetic rats. IBMX (3-isobutyl-1-methylxanthine)
      induced relaxation response was slightly but significantly attenuated in diabetic
      rats. The relaxation of the basilar artery caused by sodium nitroprusside was not
      significantly different between control and diabetic rats. In the present study,
      we were the first to report that the endothelium-dependent relaxation of the
      isolated rat basilar artery in response to ACh was significantly impaired during
      STZ-induced diabetic rats.

PMID- 9029671
TI  - Binding of tacrolimus (FK506) with human plasma proteins re-evaluation and effect
      of mycophenolic acid.
AB  - Protein binding of tacrolimus (FK506) in human plasma was re-evaluated by
      equilibration dialysis and compared with that of FK506 previously reported by two
      different methods (about 99 and 77% by an ultrafiltration and ultracentrifugation
      method, respectively). The binding determined in this study was about 99%
      irrespective of FK506 concentrations added (0.5-10 ng/ml) and this value was very
      close to that estimated by the ultrafiltration method. The effect of mycophenolic
      acid (MPA, an active form of the immunosuppressant mycophenolate mofetil) and its
      glucuronide (MPAG, a major metabolite of mycophenolate mofetil in human plasma)
      on the binding was studied at concentration levels of 1 and 10 ng/ml of FK506.
      The binding was not affected significantly by the addition of MPA (25-100
      micrograms/ml) and/or MPAG (100-1500 micrograms/ml). FK506 has already been
      reported not to cause significant changes of plasma protein binding of MPA. The
      results indicate that the unbound fraction of FK506 is about 1% in human plasma
      and that concomitant administration of FK506 and mycophenolic mofetil does not
      cause the drastic change of the binding of FK506 and MPA with human plasma
      proteins.

PMID- 9029672
TI  - The effect of copper on zinc in liver and in metallothionein.
AB  - The question as to the increase in zinc content in metallothionein in response to
      copper injection was examined. Each rat was injected intraperitoneally once with
      0.9% NaCl or copper (2, 4 or 6 mg copper/kg b.w.). After copper injection, 54.0
      62.9% of the hepatic zinc contents were found in the cytosol. Although the zinc
      contents in the cytosol and livers of copper-injected rats were higher than those
      of control rats, they did not increase in response to copper injection. The
      distribution profiles of the hepatic cytosol of copper-injected rats on a
      Sephadex G-75 column showed that the amount of the increased zinc was
      attributable to the metallothionein and high molecular weight protein fractions.
      Although the zinc contents in hepatic metallothionein of copper-injected rats
      were higher than those of control rats, they did not increase in response to
      copper injection. These results indicate that zinc contents in liver and in
      metallothionein did not increase in response to copper injection.

PMID- 9029673
TI  - The effect of cadmium on zinc and copper in liver and in metallothionein.
AB  - The question as to the increase in zinc and copper contents in metallothionein in
      response to cadmium injection was examined. Each rat was injected
      intraperitoneally once with 0.9% NaCl or cadmium (1, 2 or 3 mg cadmium/kg b.w.).
      After cadmium injection, 51.4-60.4% of the hepatic zinc contents were found in
      the cytosol. Although the zinc contents in the cytosol and livers of cadmium
      injected rats were higher than those of control rats, they did not increase in
      response to cadmium injection. Approximately 56.1-65.6% of the copper contents in
      the livers were detected in the cytosol. The copper contents in cytosol and
      livers of cadmium-injected rats did not increase in response to cadmium
      injection. The distribution profiles of the hepatic cytosol of cadmium-injected
      rats on a Sephadex G-75 column showed that the amount of the increased zinc was
      attributable to the MT fraction. Although the zinc contents in hepatic MT of
      cadmium-injected rats were higher than those of control rats, they did not
      increase in response to cadmium injection. These results indicate that zinc and
      copper contents in metallothionein did not increase in response to cadmium
      injection.

PMID- 9029674
TI  - Antioxidant effects of vitamin C in mice following X-irradiation.
AB  - The influence of supplemental vitamin C on the survival of nucleated bone marrow
      cells was examined in Swiss Webster mice following whole-body sublethal X
      irradiation (3.5 Gy). The vitamin protected these cells by a factor of 1.7 when
      cell count per tibia was taken as the biological end point. However, in studies
      with lethal whole-body irradiation (9 Gy) and 30 day survival as the end point,
      supplemental ascorbic acid (AA) had no significant effect on the biological
      outcome. Based on these studies, it appears that vitamin C is effective in
      protecting the nucleated cells at lower doses, but not at lethal doses. Studies
      on the mechanism of radioprotection by vitamin C at sublethal doses were carried
      out by following the response of endogenous AA and glutathione levels to X
      irradiation (3.5 Gy) on mice fed with regular as well as vitamin C rich diet. The
      results suggest that i) a glutathione controlled feedback mechanism regulates the
      plasma AA levels in mice; ii) the role of vitamin C against radiation damage is
      not only in the initial stages of radical scavenging but also in cellular redox
      processes mediated by glutathione.

PMID- 9029675
TI  - Effect of probucol on the cytological and biochemical changes induced by
      adriamycin in Swiss albino mice.
AB  - Probucol [(4,4'-(-(isopropylidenedithio) bis (2,6-di-t-butylphenol)], a
      hypolipidemic drug, was evaluated for its effects on the clastogenic activity of
      ADM in Swiss albino mice. Male mice were treated i.p. with different doses (25,
      50 and 100 mg/kg, body weight/day) of probucol for 7 days. Some of the mice in
      each dose group of probucol and those in the positive control group were injected
      i.p. with Adriamycin (ADM, 8 mg/kg, body weight) and killed after 24 hr. Femoral
      cells of mice were collected and studied for the frequency of micronuclei and the
      ratio of polychromatic erythrocytes to Normochromatic erythrocytes. Furthermore,
      proteins, DNA, RNA, Malondialdehyde (MDA) and non-protein sulfhydryl (NP-SH)
      levels were determined in the hepatic cells. Probucol treatment failed to induce
      any significant clastogenic, cytotoxic and biochemical changes. However, pre
      treatment with probucol was found to reduce the ADM-induced micronuclei without
      any alteration in its cytotoxicity. The DNA, RNA, proteins and NP-SH levels in
      the hepatic cells of these animals were increased and the MDA concentrations were
      reduced. The inhibition of ADM-induced clastogenicity by probucol may be
      attributed to its lipids lowering, iron chelating, free radical scavenging and
      topoisomerase-II-depleting action.

PMID- 9029676
TI  - Concentration dependence of the metabolic effects of diltiazem in the isolated
      perfused rat liver.
AB  - The concentration dependence of the effects of diltiazem on glycogenolysis,
      glycolysis, gluconeogenesis and oxygen uptake was investigated in the isolated
      perfused rat liver. The effects of this compound were very complex. At low
      concentrations diltiazem increased glycolysis, glycogenolysis (up to 200 microM)
      and oxygen uptake (up to 100 microM) in livers from fed rats. At the
      concentrations of 500 and 750 microM the drug inhibited glycolysis,
      glycogenolysis and oxygen uptake. In livers from fasted rats diltiazem inhibited
      gluconeogenesis from pyruvate. Inhibition was virtually complete at a
      concentration of 500 microM. Lactate production from pyruvate and oxygen uptake
      were also inhibited. Several alterations were observed after cessation of the
      infusion of diltiazem (i.e., a posteriori effects). The most prominent of these
      effects was an activation of glucose release in livers from fed rats
      (glycogenolysis), which occurred after cessation of the infusion of 500 or 750
      microM diltiazem. It can be concluded that diltiazem is primarily an inhibitor of
      energy metabolism in the liver. At high concentrations it blocks the respiratory
      chain. At low concentrations it could be acting as an uncoupler, because
      inhibition of a biosynthetic process (gluconeogenesis) occurred at concentrations
      (up to 200 microM) that simultaneously increased oxygen uptake and glycolysis.

PMID- 9029677
TI  - Determination of a new antiulcer agent, YJA-20379-2, in human plasma and urine by
      high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method was developed for the
      determination of a new antiulcer agent, YJA-20379-2, in human plasma and urine.
      The sample preparation was simple: 2.5-volume of acetonitrile was added to the
      biological sample to deproteinize. A 50-microliter aliquot of the supernatant was
      injected onto a C18 reversed-phase column. The mobile phase employed was methanol
      0.1M Sorensen phosphate buffer of pH 7.0-H2O (75:2:25, v/v/v), and was run at a
      flow-rate of 1.0 ml/min. The column effluent was monitored by ultraviolet
      detector at 295 nm. The retention time for YJA-20379-2 was approximately 7.0 min.
      The detection limits for YJA-20379-2 in human plasma and urine were both 100
      ng/ml. The coefficients of variation of the assay (within-day and between-day)
      were generally low (below 9.16%) for both the human plasma and urine. No
      interference from endogenous substances was found.

PMID- 9029678
TI  - Chromosome abnormalities associated with recurrent abortion.
AB  - We analyzed 37 cases of habitual abortion which were presented in our department
      in the last 2-years. Seven among 37 couples with habitual abortion exhibited
      chromosomal anomalies.

PMID- 9029679
TI  - Hepatocyte nuclear factor-4 alpha gene mutations in Japanese non-insulin
      dependent diabetes mellitus (NIDDM) patients.
AB  - A mutation in the hepatocyte nuclear factor-4 alpha (HNF-4 alpha) gene has been
      recently reported to cause maturity-onset diabetes of the young (MODY) (Yamagata,
      Furuta, et al., 1996). The mutation can also be a good candidate for the
      responsible gene of non-insulin dependent diabetes mellitus (NIDDM). The
      existence of the mutated allele of Q268X (C to T substitution within the exon 7
      of HNF-4 alpha gene) was searched in 514 alleles of Japanese NIDDM patients by
      polymerase chain reaction-restriction fragment length polymorphism analysis. No
      mutation was found in these patients. The result showed that the Q268X mutation
      of HNF-4 alpha gene was not frequent among general NIDDM patients and that it
      cannot serve as the major diabetogenic gene in the Japanese ethnic group.

PMID- 9029704
TI  - Diabetes in the 1990s--an overview.
AB  - Diabetes affects more than 16 million persons in the United States and touches
      all ages races and both genders. As a rule the younger population (usually under
      age 30) has insulin-dependent diabetes mellitus (IDDM, sometimes referred to as
      Type I diabetes) while the older population is affected by non-insulin-dependent
      diabetes mellitus (NIDDM, or Type II). Diabetes mellitus has been increasing
      fairly steadily over the years, and in 1994 the number of diabetes deaths was 5
      percent higher than in 1993. In the United States minority groups particularly
      Native Americans are more frequently affected by NIDDM than non-Hispanic whites.
      Uncontrolled diabetes often leads to long-term complications which account for an
      increase in health care costs. In 1992 diabetes and its long-term complications
      cost $92 billion approximately 15 percent of the total U.S. health care costs.
      This cost is expected to continue rising as the number of diabetics increases.
      Over the past five to seven years the disease has become more manageable with the
      development of new options medications and simple accurate diagnostic kits for
      patients home use. Research is leading to better preventive and management
      techniques which increase the need not only for general public health but also
      for individual patient education. Effective preventive measures as well as
      symptom identification and awareness can result in far better control of
      complications.

PMID- 9029705
TI  - Trends and characteristics of births attended by midwives.
AB  - In 1994 there were 218,466 births attended by midwives in the United States more
      than seven times the number in 1975 (29,413). The percent of all births attended
      by midwives rose from 0.9 percent in 1975 to 5.5 percent in 1994. The vast
      majority of midwife attended births were by certified nurse-midwives (CNMs) and
      occurred in hospitals. Births attended by other midwives comprised only 6 percent
      of all midwife-attended births (down 11 percent since-1989) and are becoming
      increasingly concentrated in out of hospital settings, particularly residences.
      Due in large part to population characteristics, the proportions of births
      attended by midwives varies markedly between states. The percentages range from
      19 percent in New Mexico to less than 1 percent in Kansas Louisiana Missouri and
      Nebraska Mothers with midwife attended births in out of hospital settings
      generally had demographic and lifestyle characteristics that were lower risk for
      obstetric complications and poor birth outcomes compared with mothers with
      physician- or midwife attended births in hospitals. That is these mothers were
      more likely to be married older more educated having higher order births and were
      less likely to smoke and gain and adequate amount of weight during pregnancy.
      However women with midwife attended births regardless of type of midwife or birth
      setting were more likely to initiate prenatal care later in the pregnancy and
      have fewer overall visits than were women whose births were attended by
      physicians. Despite less prenatal care a smaller proportion of babies whose
      births were attended by midwives were preterm or were of low or very low birth
      weight.

PMID- 9029706
TI  - Average charges for coronary artery bypass grafts and percutaneous transluminal
      coronary angioplasties, 1995.
AB  - In 1995 the average charge for a coronary artery bypass graft (CABG) among 1,643
      patients age 30 and over was $44,820. This charge was more than twice that for
      3,569 patients undergoing a percutaneous transluminal coronary angioplasty (PTCA)
      $20,370. The Middle Atlantic area reported the highest average charge for a CABG
      (18 percent above the norm) due mainly to the high charge in Pennsylvania, which
      was 37 percent higher than the national average. Each of the four regions west of
      the Mississippi River had higher than average charges for both revascularization
      procedures. The lowest charge for a CABG was reported in West Virginia-36 percent
      below the average and less than half the Pennsylvania charge Arizona, California
      and Illinois had the highest average PTCA charges, each 20 percent or more above
      that for the U.S. The lowest PTCA charge was reported in Ohio ($14,680), 28
      percent lower than the U.S. average and 42 percent lower than in Arizona Hospital
      charges accounted for 73 percent of the total CABG charge and 77 percent of the
      PTCA total. Physician charges were the highest in New York and New Jersey for
      CABGs (each 31 percent above the average) and the lowest in Colorado (37 percent
      below). For PTCAs, the physicians' fees were the highest in Indiana, Connecticut
      and New York (between 18 and 21 percent above the norm) and lowest in Washington
      (25 percent below). CABG patients remained hospitalized for 8.32 days, more than
      twice the number of days for the PTCA (3.86 days).

PMID- 9029707
TI  - A look at income and wealth in America.
AB  - Diverse forces in the U.S. economy have led to a tendency for increased
      concentration of income and wealth in the upper income brackets. Some mobility
      within classes helps to mitigate the problem, but sluggish growth of real incomes
      has heightened awareness of this trend. Even though the vast majority of
      Americans continue to identify themselves as "middle class," this slowed growth
      contributes to the concerns about the shrinking size of this group. Between 1975
      and 1995 the highest quintile of households was the only one to experience a
      growing share of money income, with virtually all of the increase occurring
      within the top 5 percent. Education and training in our high-technology society
      are two key elements in improving income. Demographic forces may also change
      income and wealth dynamics in the future particularly as the population ages and
      the ratio of workers to the elderly retired affects the supply demand forces in
      the labor markets.

PMID- 9029708
TI  - Regulation of expression of the steroidogenic acute regulatory protein (StAR)
      gene: a central role for steroidogenic factor 1.
AB  - Steroidogenic acute regulatory protein (StAR) plays a critical role in regulating
      the rate-limiting step in steroid hormone synthesis, cholesterol side-chain
      cleavage. StAR gene expression is transcriptionally controlled in the gonads by
      gonadotropic hormones via a cAMP second message. We have begun to analyze factors
      responsible for the transcriptional activation of the StAR gene. The human StAR
      gene promoter has at least two cis elements that govern basal and cAMP-regulated
      gene expression. One of these elements (the distal element) is a consensus
      binding sequence for the orphan nuclear receptor transcription factor,
      steroidogenic factor 1 (SF-1); the other (the proximal element) is a related
      motif. The human StAR promoter is not active in BeWo choriocarcinoma cells, but
      is functional and cAMP-responsive in murine Y1 adrenal cortical tumor cells.
      Cotransfection of a plasmid expressing SF-1 allows a StAR promoter construct to
      function in BeWo cells. Other orphan nuclear transcription factors do not support
      StAR promoter function in BeWo cell hosts. Deletion or mutation of the distal and
      proximal cis elements individually substantially reduces SF-1-supported StAR
      promoter activity. The distal site binds SF-1 with high affinity, whereas the
      proximal site binds SF-1 with lower affinities. These findings demonstrate a
      requirement for SF-1 for human StAR gene expression.

PMID- 9029709
TI  - Control of cholesterol access to cytochrome P450scc in rat adrenal cells mediated
      by regulation of the steroidogenic acute regulatory protein.
AB  - Cholesterol conversion to pregnenolone by cytochrome P450scc in steroidogenic
      cells, including those of the adrenal cortex, is determined by hormonal control
      of cholesterol availability. Intramitochondrial cholesterol movement to P450scc,
      which retains hormonal activation in isolated mitochondria, is apparently
      dependent on peripheral benzodiazepine receptor and the recently cloned
      steroidogenic acute regulatory (StAR) protein. In rat adrenal cells, StAR is
      formed as a 37-kDa precursor that is transferred to the mitochondrial inner
      membrane following phosphorylation by hormonally activated protein kinase A, and
      processed to multiple forms, some of which turn over very rapidly. In bovine
      cells, StAR undergoes three modifications forming a set of eight proteins seen in
      both glomerulosa and fasciculata cells. In the former, cyclic AMP and angiotensin
      II each decrease two forms and elevate six forms. Significantly, the major change
      seen after activation may not involve phosphorylation of StAR. Cholesterol
      transfer across mitochondrial membranes is also activated in isolated
      mitochondria by GTP and low concentrations of Ca2+, apparently prior to
      activation by StAR. Depletion of StAR by cycloheximide inhibits cholesterol
      transfer but is overcome by uptake of Ca2+ into the matrix. This activation of
      cellular cholesterol transport is sustained in adrenal cells permeabilized by
      Streptolysin O. In rat adrenal cells cAMP elevates 3.5- and 1.6-kb mRNA,
      hybridized by a 1.0-kb StAR cDNA. A 3.5-kb rat adrenal cDNA that encodes all
      except the 5' end of the longest StAR mRNA has been characterized. The
      corresponding gene sequence is distributed across seven exons. The shorter mRNA
      may arise from polyadenylation signals early in exon 7. However, the 3.5-kb mRNA
      comprises 80-90% of untreated rat adrenal StAR mRNA and may therefore provide the
      prime source for in vivo translation of StAR protein.

PMID- 9029710
TI  - Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis.
AB  - Steroidogenesis begins with the metabolism of cholesterol to pregnenolone by the
      inner mitochondrial membrane cytochrome P450 side-chain cleavage (P450scc)
      enzyme. The rate of steroid formation, however, depends on the rate of
      cholesterol transport from intracellular stores to the inner mitochondrial
      membrane and loading of P450scc with cholesterol. In previous in vitro studies,
      we demonstrated that a key element in the regulation of cholesterol transport is
      the mitochondrial peripheral-type benzodiazepine receptor (PBR). We also showed
      that the polypeptide diazepam binding inhibitor (DBI), an endogenous PBR ligand,
      stimulates cholesterol transport and promotes loading of cholesterol to P450scc
      in vitro, and that its presence is vital for hCG-induced steroidogenesis by
      Leydig cells. Based on these data and the observations that i) the mitochondrial
      PBR binding and topography are regulated by hormones; ii) the 18-kDa PBR protein
      is functionally coupled to the mitochondrial contact site voltage-dependent anion
      channel protein; iii) the 18-kDa PBR protein is a channel for cholesterol, as
      shown by molecular modeling and in vitro reconstitution studies; iv) targeted
      disruption of the PBR gene in steroidogenic cells dramatically reduces the
      ability of the cells to transport cholesterol in the mitochondria and produce
      steroids; v) endocrine disruptors, with known anisteroidogenic effect, inhibit
      PBR ligand binding; and vi) in vivo reduction of adrenal PBR expression results
      in reduced circulating glucocorticoid levels, we conclude that PBR is an
      indispensable element of the steroidogenic machinery.

PMID- 9029711
TI  - The role of the steroidogenic acute regulatory protein in steroidogenesis.

PMID- 9029712
TI  - Transcriptional regulation of the CYP11A1 and ferredoxin genes.
AB  - The first step in the synthesis of all steroids is the cleavage of cholesterol
      side chain, catalyzed by an electron transport system located in mitochondria
      consisting of ferredoxin reductase, ferredoxin, and cytochrome P450scc. These
      proteins are present in adrenal, gonad, placenta, and some parts of the brain. In
      addition, ferredoxin and ferredoxin reductase are also found in the kidney and
      liver. Whereas ferredoxin reductase levels remain constant in the cell,
      ferredoxin and P450scc levels are stimulated by trophic hormones using cAMP as an
      intracellular messenger. The ferredoxin promoter is relatively simple, consisting
      of a TATA box and two Sp1-binding sites. This simple module is enough to direct
      cAMP-dependent transcription in a steroidogenic cell-specific fashion. The
      regulatory region for the P450scc gene is more complex, containing many protein
      binding sites for different regulation purposes. Its TATA box directs cAMP
      dependent transcription in a cell-type-specific manner. A transcription factor,
      steroidogenic factor 1 (SF1), activates P450scc gene expression. The tissue
      specific expression of the P450scc gene is probably accomplished through the
      interaction of SF1 with other protein factors located further upstream of the
      control region. SF1 may also be involved in the cAMP response. An upstream region
      binding to cAMP-Responsive Element Binding Protein CREB and AP1 can respond to
      cAMP for gene activation. These analyses of regulatory elements provide the
      structural architecture for transcriptional regulation of the ferredoxin and the
      CYP11A11 gene.

PMID- 9029713
TI  - Transcriptional regulation of the bovine CYP17 gene by cAMP.
AB  - The transcription of steroid hydroxylase genes is controlled by ACTH and cAMP in
      the adrenal cortex. In most instances the regulation appears to rely on
      transcription factors traditionally not associated with cAMP-dependent gene
      expression. For the non-traditional factors it remains necessary to elucidate the
      coupling of increases in intracellular cAMP and cAMP-dependent protein kinase
      (PKA) activity to the function of these proteins. The bovine CYP17 gene, which
      encodes the steroid 17 alpha-hydroxylase, contains two discrete DNA elements
      within its promoter and upstream region (CRS1 and CRS2) that individually can
      confer cAMP responsiveness. The CRS1 element is a target for PKA signalling and
      for negative regulation via the protein kinase C signal transduction pathway. The
      homeodomain protein Pbx1 enhances CRS1-dependent transcription, but additional
      CRS1-binding proteins remain to be identified. Furthermore it is not known how
      PKA regulates the activity of Pbx1 or its possible binding partners. Closer to
      the promoter, the nuclear orphan receptors SF-1 and COUP-TF have overlapping
      binding sites in CRS2 and they bind in a mutually exclusive manner with very
      similar affinities; 8 and 10 nM, respectively. SF-1 stimulates whereas COUP-TF
      inhibits transcription from the bovine CYP17 promoter. Together, the data suggest
      that cAMP-dependent control of the amounts of the activator SF-1 vs. the
      repressor COUP-TF could influence CRS2-dependent transcription. In addition, PKA
      may influence the phosphorylation of SF-1, thus increasing its activity. In
      vitro, PKA will elicit phosphorylation of SF-1. However, although SF-1 can be
      immunoprecipitated from adrenocortical cells as a phosphroprotein, we have not
      been able to show cAMP-dependent increase in net phosphorylation in intact cells.
      More careful examination of individual phosphorylation sites in SF-1 may still
      reveal hormone- and cAMP-induced phosphorylation of SF-1.

PMID- 9029714
TI  - The testis and the adrenal are (transcriptionally) the same.
AB  - We have been studying the transcriptional regulation of the rat P450c17 gene in
      both adrenocortical and Leydig cells, to assess which DNA sequences are required
      for its basal and hormonally stimulated transcription. Comparing the
      transcriptional regulation in both of these cell types enables us to demonstrate
      whether specific nuclear factors required for transcriptional regulation of the
      rat P450c17 gene are tissue-specifically expressed, and whether the same cis
      acting DNA elements in the gene are required for transcriptional regulation in
      both of these two different steroidogenic tissues. Using such an approach, we
      previously demonstrated that the transcriptional regulation of the rat P450scc
      gene uses different cis-acting DNA sequences in steroidogenic versus neural
      tissues, and requires the expression of tissue-specific nuclear factors that are
      unique to neural tissue. However, in studying the transcriptional regulation of
      the rat P450c17 gene in cultured mouse adrenocortical Y-1 and mouse Leydig MA-10
      cells, we have shown that identical DNA sequences necessary for basal and cAMP
      stimulated transcriptional regulation in these two cell types, and that identical
      nuclear factors from Y-1 and from MA-10 cells bind to these sequences. We have
      identified four transcriptionally active regions within 500 bp of the
      transcription initiation start site that are important for basal and/or cAMP
      stimulated transcriptional regulation of this gene in Y-1 and MA-10 cells. This
      paper will discuss two of these regions in greater detail. By studying the
      regulation of the rat P450c17 gene, we have identified two new members of the
      orphan nuclear receptor gene family and have discovered new alternative
      mechanisms by which orphan nuclear receptors activate gene transcription in both
      mouse adrenocortical Y-1 and Leydig MA-10 cells.

PMID- 9029715
TI  - Steroidogenic factor 1 acts at all levels of the reproductive axis.
AB  - The conversion of cholesterol into steroid hormones occurs through the sequential
      actions of the cytochrome P450 steroid hydroxylases. Attempts to understand the
      mechanisms responsible for the temporal and spatial expression patterns of these
      enzymes led to the identification of a shared regulator, termed steroidogenic
      factor 1 (SF-1). SF-1 coordinately regulates the steroid hydroxylase genes and
      thus functions as a global mediator of steroidogenesis. Of greater significance,
      recent studies using a knockout mouse model have further implicated SF-1 in a
      variety of processes ranging from development of the steroidogenic organs to the
      normal function of gonadotropes and the development of the ventromedial
      hypothalamic nucleus. A fundamental aspect of elucidating the role of SF-1 at all
      levels of the reproductive axis is to identify its cell-specific target genes.
      The recent purification and cloning of the steroidogenic acute regulatory (StAR)
      protein has provided an intriguing new candidate through which SF-1 acts to
      mediate its effects on reproductive competence. These studies yield novel
      insights into the processes of steroidogenesis, endocrine development, and
      reproductive function.

PMID- 9029716
TI  - Expression of cytochromes P450aldo and P45011 beta in rat adrenal gland during
      late gestational and neonatal stages.
AB  - The development of the rat adrenal gland during late gestational and neonatal
      stages was studied by following the expression of aldosterone synthase cytochrome
      P450 (P450aldo) and glucocorticoid-synthesizing cytochrome P450 (P45011 beta).
      Cells expressing P450aldo, a functional marker for the mineralocorticoid
      synthesizing zona glomerulosa, were not detected until day 20 of fetal age, i.e.,
      2 days before birth, although the zona glomerulosa cells were histologically
      recognizable at the 18th day of gestation. The intensity of P450aldo staining
      thereafter became stronger with age in the outer portion of the cortex. Cells
      expressing P45011 beta, a marker for the glucocorticoid-producing zona
      fasciculata, were present in the fetal adrenals on the 18th day. P45011 beta
      positive cells were distributed over the whole adrenal gland and intermingled
      with the cells containing tyrosine hydroxylase, a marker enzyme for medullary
      cells. The P45011 beta-positive and tyrosine hydroxylase-positive cells began to
      separate on the 20th day, and were completely resolved from each other around the
      third day after birth. Expression of P450aldo and P45011 beta, together with that
      of tyrosine hydroxylase, thus serves as a suitable marker for studying the
      development of the adrenal gland.

PMID- 9029717
TI  - Role of growth factors in the developmental regulation of the human fetal adrenal
      cortex.
AB  - Development of the human fetal adrenals is characterized by rapid growth and high
      levels of steroidogenic activity during the latter two-thirds of pregnancy. By
      midgestation, the human fetal adrenals are composed of two distinct cortical
      zones: the predominant fetal zone, which occupies 80-90% of the cortical volume
      and produces large amounts of the delta 5-steroid dehydroepiandrosterone sulfate,
      and the narrow definitive zone, which surrounds the fetal zone. Late in
      gestation, the peripheral portion of the fetal zone develops into a third,
      functionally distinct compartment, the transitional zone, which is the likely
      site of cortisol synthesis. Soon after birth, the adrenal cortex is remodeled and
      the fetal zone disappears. The adult cortical zones are thought to arise from the
      definitive zone, which persists postnatally. Development of the human fetal
      adrenals is regulated primarily by corticortropin (ACTH) secreted from the fetal
      pituitary. However, as ACTH is not a mitogen per se, its proliferative actions on
      human fetal adrenal cortical cells are thought to be mediated by
      autocrine/paracrine growth factors produced by adrenal cortical cells in response
      to ACTH. In addition, these growth factors appear to modulate the functional
      response of fetal adrenal cortical cells to ACTH. The roles of several growth
      factors, including the insulin like growth factors I and II (IGF-I and IGF-II),
      epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), activin,
      inhibin, and the transforming growth factors alpha and beta (TGF-alpha and TGF
      beta) have been examined. In cultured human fetal adrenal cortical cells, EGF,
      bFGF, and IGF-I and -II are mitogenic, whereas activin and TGF-beta inhibit
      proliferation. IGF-II, activin, and TGF-beta also modulate ACTH-stimulated
      steroidogenesis. Human fetal adrenal cortical cells express IGF-II, bFGF and the
      activin/inhibin subunits, and the abundance of mRNAs for each of these factors is
      up-regulated by ACTH, suggesting that these growth factors are
      autocrine/paracrine mediators of ACTH action. Thus, although human adrenal
      development is primarily regulated by ACTH, its actions appear to be
      mediated/modulated by a cohort of locally expressed growth factors, the net
      effect of which results in the unique growth and steroidogenic activity of the
      human fetal adrenal cortex.

PMID- 9029718
TI  - Zona glomerulosa-specific factor: cloning and function.
AB  - The rat adrenal cortex is composed of three zones: the zona glomerulosa, the zona
      fasciculata, and the zona reticularis. Several investigators have claimed the
      presence of a zona intermedia between the zonae glomerulosa and fasciculata. The
      cells of zona glomerulosa, a few layers of cells just beneath the adrenal
      capsule, synthesize and secrete aldosterone, whereas those of zonae fasciculata
      and reticularis secrete glucocorticoids and androgens, respectively. The function
      of the cells in zona intermedia is unclear, because they express neither
      aldosterone synthase nor 11 beta-hydroxylase. To investigate the mechanism
      underlying the zonal differentiation of adrenocortical steroidogenesis, attempts
      have been made to isolate and characterize zone-specifically expressed proteins
      such as steroidogenic enzymes and putative regulatory factors. Having subtracted
      the mRNAs present in the decapsulated adrenal gland from those in the adrenal
      capsule, we successfully isolated three distinct clones, each specifically
      expressed in the zona glomerulosa. One clone encoded a protein named zona
      glomerulosa-specific factor (ZOG), which had a putative signal peptide at the N
      terminus, six tandem epidermal growth factor (EGF)-like repeats, and a
      transmembrane domain in the central portion and a short cytosolic stretch at the
      C-terminus. Immunohistochemical studies using the antibody raised against ZOG
      confirmed the presence of the protein in all layers of cells in the zona
      glomerulosa. In contrast, cells possessing aldosterone synthase were present only
      in the periphery of zona glomerulosa, just beneath the capsule. These findings
      suggest that there are at least two kinds of zona glomerulosa cells in the rat
      adrenal cortex, one expressing aldosterone synthase as well as ZOG, and another
      expressing only ZOG. The cells in the zona intermedia did not express ZOG,
      aldosterone synthase, or 11 beta-hydroxylase, but did express Ad4BP. ZOG was not
      detected in zonae fasciculata and reticularis where 11 beta-hydroxylase was
      present.

PMID- 9029719
TI  - Human 11 beta-hydroxysteroid dehydrogenase: studies on the stably transfected
      isoforms and localization of the type 2 isozyme within renal tissue.
AB  - The type 1 and type 2 isoforms of human 11 beta-hydroxysteroid dehydrogenase (11
      beta-HSD) play a crucial role, respectively, in modulating glucocorticoid and
      mineralocorticoid hormone action. Deficiency of the 11 beta-HSD2 isoform, as
      described in the syndrome of apparent mineralocorticoid excess and following
      liquorice (glycyrrhetinic acid) or carbenoxolone ingestion, results in
      hypertension in which cortisol acts as a potent mineralocorticoid. Several
      studies have addressed the effects of progesterone, glycyrrhetinic acid, and
      their derivatives on 11 beta-HSD activity, but these were largely undertaken
      before the characterization of the 11 beta-HSD isoforms. The aim of this study
      was to evaluate the localization of 11 beta-HSD2 in human kidney and to study the
      effects of progesterone, glycyrrhetinic acid, and their related compounds on
      stable transfectants of the human 11 beta-HSD isoforms. Using an in-house sheep
      antibody against human 11 beta-HSD2, immunoperoxidase studies localized 11 beta
      HSD2 to renal cortical and medullary collecting ducts. Glomeruli, vascular
      structures, loops of Henle, and proximal tubules were all negative. Confocal
      laser microscopy studies indicated both a cytoplasmic and nuclear localization
      for the enzyme within renal collecting ducts. The nuclear staining, which was
      intranuclear and was not associated with the nuclear membrane, accounted for 40%
      of the total cellular 11 beta-HSD2 immunoreactivity. Kinetic analysis of 11 beta
      HSD activity in fetal kidney 293 cells stably transfected with h11 beta
      HSD1/pcDNA3 or 11 beta-HSD2/pCR3, indicated, respectively, low-affinity
      dehydrogenase/oxoreductase activity (Km for F, 1.8 microM; Km for E, 270 nM) and
      high-affinity dehydrogenase activity (Km for F, 190 nM). The reductase activity
      of 11 beta-HSD1 was inhibited by 11 alpha-hydroxyprogesterone > carbenoxolone =
      glycyrrhetinic acid = progesterone > 11 beta-hydroxyprogesterone. The
      dehydrogenase activity of 11 beta-HSD2 was inhibited 11 alpha-hydroxyprogesterone
      = 11 beta-hydroxyprogesterone > glycyrrhetinic acid > carbenoxolone =
      progesterone. 11 beta-HSD2, expressed in the renal collecting duct, serves to
      protect the mineralocorticoid receptor (MR) in an autocrine fashion. The
      demonstration of a nuclear localization for what was thought to be principally a
      microsomal enzyme suggests that interaction between the MR and its ligand (either
      aldosterone or cortisol) may be a nuclear rather than a cytoplasmic event. The
      inhibitory effects of progesterone, glycyrrhetinic acid, and related compounds on
      11 beta-HSD1 and 2 were similar, and it remains to be seen what implication these
      findings have for 11 beta-HSD1 action in tissues such as the liver and gonad and
      renal 11 beta-HSD2 activity in relation to sodium homeostasis and blood pressure
      control.

PMID- 9029720
TI  - Molecular analysis of 11 beta-hydroxysteroid dehydrogenase and its role in the
      syndrome of apparent mineralocorticoid excess.
AB  - The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of
      hypertension in which 11 beta-hydroxysteroid dehydrogenase (11-HSD) is defective.
      This enzyme converts cortisol to its inactive metabolite, cortisone. The
      deficiency allows mineralocorticoid receptors to be occupied by cortisol, because
      these receptors themselves have similar affinities for cortisol and aldosterone.
      There are two isozymes of 11-HSD, a liver (L) or type 1 isozyme with a relatively
      low affinity for steroids, and a kidney (K) or type 2 isozyme with high steroid
      affinity. Mutations in the gene for the kidney isozyme of 11-HSD have been
      detected in all kindreds with AME. We expressed enzymes carrying all known
      missense mutations in cultured cells and determined their activity. For each
      patient with AME, we compared the enzymatic activity predicted by the genotype
      with the ratio of cortisol to cortisone metabolites in the urine, (THF +
      aTHF)/THE. These were strongly correlated, suggesting that the biochemical
      phenotype of AME is largely determined by genotype. The K isozyme of 11-HSD is
      also expressed in high levels in the placenta, where its function is unclear. AME
      patients often have low birth weight. By analogy with AME, low placental 11-HSD K
      activity in humans might be a risk factor for low birth weight and subsequent
      hypertension. However, we found that there was no significant correlation between
      11-HSD activity, mRNA levels, and either fetal or placental weight.

PMID- 9029721
TI  - Glucocorticoids, feto-placental 11 beta-hydroxysteroid dehydrogenase type 2, and
      the early life origins of adult disease.
AB  - Increasing human epidemiological data suggest that events that subtly retard
      intrauterine growth may determine common disorders, such as hypertension and non
      insulin-dependent diabetes, in adult life. The underlying mechanisms are unknown.
      However, excessive fetal exposure to glucocorticoids retards growth and
      "programs" adult hypertension in rats. 11 beta-Hydroxysteroid dehydrogenase type
      2 (11 beta-HSD2) catalyzes the rapid inactivation of cortisol and corticosterone
      to inert 11 keto-products. Normally, 11 beta-HSD2 in the placenta and some fetal
      tissues is thought to protect the fetus from excess maternal glucocorticoids. In
      both rats and humans there is considerable natural variation in placental 11 beta
      HSD2, and enzyme activity correlates with birth weight. Moreover, inhibition of
      feto-placental 11 beta-HSD2 in the rat reduces birth weight and produces
      hypertensive and hyperglycaemic adult offspring, many months after prenatal
      treatment; effects are dependent upon intact maternal adrenals, suggesting a
      direct action on the fetus or placenta. Maternal protein restriction during
      pregnancy also produces hypertensive offspring and selectively attenuates
      placental 11 beta-HSD2 activity. These data suggest that feto-placental 11 beta
      HSD2, by regulating fetal exposure to maternal glucocorticoids, crucially
      determines fetal growth and the programming of later disorders. Deficiency of the
      barrier to maternal glucocorticoids may represent a common pathway between the
      maternal environment and feto-placental programming of later disease. These data
      may, at least in part, explain the human observations linking early life events
      to the risk of subsequent disease.

PMID- 9029722
TI  - Structure and function of steroid dehydrogenases involved in hypertension,
      fertility, and cancer.
AB  - Short-chain dehydrogenase reductase (SDR) enzymes influence mammalian
      reproduction, hypertension, neoplasia, and digestion. The three-dimensional
      structures of two members of the SDR family reveal the position of the conserved
      catalytic triad, a possible mechanism of keto-hydroxyl interconversion, the
      molecular mechanism of inhibition, and the basis for selectivity. Glycyrrhizic
      acid, the active ingredient in licorice, and its metabolite carbenoxolone are
      potent inhibitors of bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3
      alpha, 20 beta-HSD). The three-dimensional structure of the 3 alpha,20 beta-HSD
      carbenoxolone complex unequivocally verifies the postulated active site of the
      enzyme, shows that inhibition is a result of direct competition with the
      substrate for binding, and provides a plausible model for the mechanism of
      inhibition of 11 beta-hydroxysteroid dehydrogenase and 15-hydroxyprostaglandin
      dehydrogenase by carbenoxolone. The structure of human 17 beta-hydroxysteroid
      dehydrogenase type 1 (17 beta-HSD) suggests the details of binding of estrone and
      17 beta-estradiol in the active site of the enzyme and the possible roles of
      various amino acids in the catalytic cleft. The SDR family includes over 50
      proteins from human, mammalian, insect, and bacterial sources. Only five residues
      are conserved in all members of the family, including the YXXXK sequence. X-ray
      crystal structures of five members of the family have been completed. When the
      alpha-carbon backbone of the cofactor binding domains of the five structures are
      superimposed, the conserved residues are at the core of the structure and in the
      cofactor binding domain, but not in the substrate binding pocket.

PMID- 9029723
TI  - Structure and function of 3 alpha-hydroxysteroid dehydrogenase.
AB  - Mammalian 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSDs) inactivate
      circulating steroid hormones, and in target tissues regulate the occupancy of
      steroid hormone receptors. Molecular cloning indicates that 3 alpha-HSDs are
      members of the aldo-keto reductase (AKR) superfamily and display high sequence
      identity (> 60%). Of these, the most extensively characterized is rat liver 3
      alpha-HSD. X-ray crystal structures of the apoenzyme and the E.NADP+ complex have
      been determined and serve as structural templates for other 3 alpha-HSDs. These
      structures reveal that rat liver 3 alpha-HSD adopts an (alpha/beta)8-barrel
      protein fold. NAD(P)(H) lies perpendicular to the barrel axis in an extended
      conformation, with the nicotinamide ring at the core of the barrel, and the
      adenine ring at the periphery of the structure. The nicotinamide ring is
      stabilized by interaction with Y216, S166, D167, and Q190, so that the A-face
      points into the vacant active site. The 4-pro-(R) hydrogen transferred in the
      oxidoreduction of steroids is in close proximity to a catalytic tetrad that
      consists of D50, Y55, K84, and H117. A water molecule is within hydrogen bond
      distance of H117 and Y55, and its position may mimic the position of the carbonyl
      of a 3-ketosteroid substrate. The catalytic tetrad is conserved in members of the
      AKR superfamily and resides at the base of an apolar cleft implicated in binding
      steroid hormone. The apolar cleft consists of a side of apolar residues (L54,
      W86, F128, and F129), and opposing this side is a flexible loop that contains
      W227. These constraints suggest that the alpha-face of the steroid would orient
      itself along that side of the cleft containing W86. Site-directed mutagenesis of
      the catalytic tetrad indicates that Y55 and K84 are essential for catalysis. Y55S
      and Y55F mutants are catalytically inactive, but still form binary (E.NADPH) and
      ternary (E.NADH.Testosterone) complexes; by contrast K84R and K84M mutants are
      catalytically inactive, but do not bind steroid hormone. The reliance on a
      Tyr/Lys pair is reminiscent of catalytic mechanisms proposed for other AKR
      members as well as for HSDs that belong to the short-chain
      dehydrogenase/reductase (SDR) family, in which Tyr is the general acid, with its
      pKa being lowered by Lys. Superimposition of the nicotinamide rings in the
      structures of 3 alpha-HSD (an AKR) and 3 alpha, 20 beta-HSD (an SDR) show that
      the Tyr/Lys pairs are positionally conserved, suggesting convergent evolution
      across protein families to a common mechanism for HSD catalysis. W86Y and W227Y
      mutants bind testosterone to the E.NADH complex, with effective increases in Kd
      of 8- and 20-fold. These data provide the first evidence that the side of the
      apolar cleft containing W86 and the opposing flexible loop containing W227 are
      parts of the steroid-binding site. Detailed mutagenesis studies of the apolar
      cleft and elucidation of a ternary complex structure will ultimately provide
      details of the determinants that govern steroid hormone recognition. These
      determinants could provide a rational basis for structure-based inhibitor design.

PMID- 9029724
TI  - Structure of cytochrome P450eryF: substrate, inhibitors, and model compounds
      bound in the active site.
AB  - Much of our understanding of P450 reaction mechanisms derives from studies on
      P450cam, a bacterial camphor hydroxylase. P450cam has served as the model for
      understanding detailed structure/function relationships in mammalian P450
      enzymes, which have not proved amenable to x-ray crystallographic techniques. To
      expand and improve the P450 model, we solved the structure of P450eryF, a
      cytochrome P450 involved in erythromycin biosynthesis. The overall structure of
      P450eryF is similar to that of P450cam, but differs in the exact positioning of
      several alpha-helices, which results in the enlargement of the substrate-binding
      pocket. P450eryF also differs from P450cam in having alanine in place of the
      highly conserved threonine residue in the active site. To assess the role of this
      alanine residue, two mutant forms of P450eryF and a substrate analog were
      examined. Our findings suggest that P450eryF has evolved an active site that
      utilizes the substrate to assist in catalysis. In addition, the enlarged
      substrate binding pocket of P450eryF enables P450eryF to bind certain steroid
      compounds and azole-based steroid hydroxylase inhibitors. Crystals have been
      obtained for P450eryF complexed with the antifungal drug ketoconazole, and the
      high-resolution structure has been determined.

PMID- 9029725
TI  - P450BM-3; a tale of two domains--or is it three?
AB  - Over 400 P450s have been identified to date in prokaryotes and eukaryotes, plants
      and animals, mitochondria and endoplasmic reticulum. These enzymes function in
      areas such as metabolism and steroidogenesis. The eukaryotic members of this gene
      superfamily of proteins have proved difficult to study because of the hydrophobic
      nature of their substrates, their various redox partners, and membrane
      association. To better understand the structure/function relationship of P450s
      what determines substrate specificity and selectivity, what determines redox
      partner binding, and which regions are involved in membrane binding-we have
      compared the three crystallized, soluble bacterial P450s (two class I and one
      class II) and a model of a steroidogenic, eukaryotic P450 (P450arom), to define
      which structural elements form a conserved structural fold for P450s, what
      determines specificity of substrate binding and redox-partner binding, and which
      regions are potentially involved in membrane association. We believe that there
      is a conserved structural fold for all P450s that can be used to model those
      P450s that prove intransigent to structural determination. However, although
      there appears to be a conserved structural core among P450s, there is sufficient
      sequence variability that no two P450s are structurally identical. NADPH-P450
      reductase transfers electrons from NADPH to P450 during the P450 catalytic cycle.
      This enzyme has usually been thought of as a simple globular protein; however,
      sequence analysis has shown that NADPH-P450 reductase is related to two separate
      flavoprotein families, ferredoxin nucleotide reductase (FNR) and flavodoxin.
      Recent studies by Wolff and his colleagues have shown that the FAD-binding FNR
      domain and FMN-binding flavodoxin domain of human NADPH-P450 reductase can be
      independently expressed in Escherichia coli. The subdomains can be used to
      reconstitute, however poorly, the monooxygenase activity of the P450 system. We
      have been utilizing the reductase domain of P450BM-3 to study the mechanism of
      electron transfer from NADPH to P450 in this complex multidomain protein. We have
      overexpressed both the FNR subdomain and the flavodoxin subdomain in E. coli and
      fully reconstituted the cytochrome c reductase activity of this enzyme. Our
      studies have shown that electron transfer from NADPH through the reductase domain
      to the P450 requires shuttling of the FMN subdomain between the reductase
      subdomain and the P450. Studies of the factors that control the molecular
      recognition and interaction among these three proteins are complicated by the
      weakness of the association and changes in the strength of the interaction
      depending on the redox state of each of the components. How these structural and
      mechanistic studies of a soluble bacterial P450 can be extended to gain a better
      understanding of the control of membrane-bound eukaryotic P450-dependent redox
      systems is discussed.

PMID- 9029726
TI  - Molecular recognition and electron transfer in mitochondrial steroid hydroxylase
      systems.
AB  - Mitochondrial monooxygenase systems are involved in the biosynthesis of
      glucocorticoids, mineralocorticoids, bile acids, and 1,25-dihydroxyvitamin D. The
      reactions are catalyzed by specific P450 enzymes that receive reducing
      equivalents via NADPH-ferredoxin oxidoreductase (adrenodoxin reductase) and
      ferredoxin (adrenodoxin). Although the three-dimensional structures of the
      individual components have not yet been solved, methods of expressing recombinant
      forms of these enzymes in Escherichia coli have allowed the use of site-directed
      mutagenesis to investigate the roles of specific amino acids in protein binding
      interactions, electron transfer, and catalysis. These studies have identified key
      charged residues in NADPH-ferredoxin oxidoreductase, ferredoxin, and P450scc,
      which are involved in electrostatic interactions critical for recognition, high
      affinity binding, and electron transfer. The finding that the binding sites on
      ferredoxin for NADPH-ferredoxin oxidoreductase and P450 show significant overlap
      supports the proposed function for ferredoxin as a mobile electron shuttle
      between the reductase and P450 enzymes and is consistent with ferredoxin's role
      in serving multiple P450 isoforms.

PMID- 9029727
TI  - Regulation of androgen synthesis: the late steroidogenic pathway.
AB  - Studies of the regulation of androgen synthesis in steroidogenic cells have
      focused on both transcriptional and post-translational regulation of the proteins
      that catalyze these reactions: the P450c17 that catalyzes the production of DHEA
      or androstenedione in consecutive hydroxylase and lyase activities, and the 17
      beta-hydroxysteroid dehydrogenase (17 beta-HSD) that catalyzes the conversion of
      androstenedione to testosterone. Our studies of the regulation of the CYP17 lyase
      activity at the molecular level have utilized species- and tissue-specific
      differences to identify target regulatory sequences. Adenovirus infection of rat
      CYP17 promoter/luciferase reporter gene constructs in primary cultures of rat
      adrenal and rat Leydig cells revealed a rat-specific domain between-1 and -108 bp
      that cause inhibition of both basal and cAMP-induced CYP17 transcription in the
      adrenal, but not the Leydig cell. In contrast, similar promoter constructs from
      other species exhibited substantial cAMP-induced transcriptional activity in the
      rat adrenal. Mutagenesis of the conserved region of the rat and human proteins
      reveals significant differences in the amino acid domains required for
      hydroxylase and lyase activities within and between the two species, consistent
      with their differential regulation of lyase activity. The 17 beta-hydroxysteroid
      dehydrogenase (17 beta-HSD) reaction requires a viable glucose transporter system
      for optimal activity, and a high-energy phosphate was discovered to be the
      requisite product of glucose metabolism in 17 beta-HSD activation. These studies
      have provided insight into potential mechanisms of control of androgen synthesis
      in the late steroidogenic pathway, at the transcriptional and post-translational
      levels.

PMID- 9029728
TI  - The regulation of 17,20 lyase activity.
AB  - P450c17 is a single microsomal enzyme that catalyzes two distinct steroid
      biosynthetic activities: 17 alpha-hydroxylase and 17,20 lyase. Human beings have
      only one gene that encodes only one form of P450c17. Three clinical observations
      indicated that these were independently regulated activities. First, several
      cases of isolated 17,20 lyase deficiency were reported, in which 17 alpha
      hydroxylase activity was spared. Second, most adrenal steroidogenesis in children
      stops after 17 alpha-hydroxylation, thus permitting the synthesis of cortisol,
      whereas most gonadal steroidogenesis proceeds to C19 sex steroids as a result of
      both activities. Third, the 17,20 lyase activity of the human adrenal is
      developmentally activated during adrenarche. To catalyze these two activities,
      P450c17 must receive reducing equivalents from electron donors (redox partners).
      Previous observations showed that the molar ratio of P450 oxidoreductase to
      P450c17 was 3-fold higher in the testis than in the adrenal, and that increasing
      the molar ratio of the redox partner to P450c17 would increase the ratio of 17,20
      lyase activity to 17 alpha-hydroxylase. We have recently shown that P450c17 must
      be phosphorylated on serine and threonine residues by a cAMP-dependent protein
      kinase to acquire 17,20 lyase activity. We have also recently found two cases of
      isolated 17,20 lyase deficiency that have mutations of residues in the proposed
      redox partner binding site. Together, these studies suggest a unified view of the
      regulation of 17,20 lyase activity. The ratio of 17,20 lyase to 17 alpha
      hydroxylase activity of P450c17 is regulated by the availability of reducing
      equivalents flowing to the enzyme. This can be increased by increasing the molar
      concentration of electron-donating redox partners, such as P450 oxidoreductase or
      possibly cytochrome b5, as appears to be the case in the gonads. Alternatively,
      the affinity of P450c17 for redox partners may be selectively increased by
      Ser/Thr phosphorylation, or selectively decreased by certain mutations in the
      redox partner binding site, in either case altering an electrostatic interaction
      between P450c17 and the redox partner. This model is consistent with all present
      observations about the biochemistry, genetics, enzymology, and clinical
      phenomenology of P450c17.

PMID- 9029729
TI  - Physiology and molecular genetics of 17 beta-hydroxysteroid dehydrogenases.
AB  - 17 beta-Hydroxysteroid dehydrogenases (17 beta-HSDs) are enzymes involved in both
      the activation and inactivation of androgens and estrogens. 17 beta-HSD type 1
      shows a high specificity for C18 steroids and is the major isozyme in the
      granulosa cells of the ovary. Its role is to convert the inactive C18 steroid
      estrone to the active estrogen estradiol, which in turn locally promotes
      maturation of the follicle. In contrast, attenuation of estradiol action in the
      glandular epithelium of the secretory endometrium is achieved by expression of
      the oxidative type 2 isozyme that inactivates estradiol to estrone. An
      interesting feature of 17 beta-HSD type 2 is that the enzyme also possesses 20
      alpha-HSD activity, i.e., it catalyzes the 20 alpha-oxidation of the inactive C21
      steroid 20 alpha-dihydroprogesterone to the active progestin progesterone. As the
      type 2 enzyme is also active on androgens, it may play a general role in the
      peripheral inactivation of androgens and estrogens, thus determining their steady
      state levels in target tissues. The reductive 17 beta-HSD type 3 is predominantly
      expressed in the testis and converts the inactive C19 steroid androstenedione to
      the active androgen testosterone. The importance of the type 3 enzyme in male
      steroid hormone physiology is underscored by the genetic disease 17 beta-HSD
      deficiency. Mutations in the 17 beta-HSD3 gene impair the formation of
      testosterone in the fetal testis and give rise to genetic males with normal male
      Wolffian duct structures but female external genitalia. To date, 15 mutations
      have been identified in 18 subjects with the disease.

PMID- 9029730
TI  - The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology.
AB  - 17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) controls the last step in the
      formation of all androgens and all estrogens. This crucial role of 17 beta-HSD is
      performed by at least five 17 beta-HSD isoenzymes having individual cell-specific
      expression, substrate specificity, regulation mechanisms, and reductive or
      oxidative catalytic activity. Both estrogenic and androgenic 17 beta-HSD
      activities were found in all 25 rhesus monkey and 15 human peripheral intracrine
      tissues examined. Type 1 17 beta-HSD is a protein of 327 amino acids catalyzing
      the formation of 17 beta-estradiol from estrone. Its x-ray structure was the
      first to be determined among mammalian steroidogenic enzymes. Initially
      crystallized with NAD, the crystal structure of type 1 17 beta-HSD has just been
      determined as a complex with 17 beta-estradiol, thereby illustrating the
      conformation of the substrate-binding site. Type 2 17 beta-HSD degrades 17 beta
      estradiol into estrone and testosterone into androstenedione, and type 4 17 beta
      HSD mainly degrades 17 beta-estradiol into estrone and androst-5-ene-3 beta, 17
      beta-diol into dehydroepiandrosterone. Types 3 and 5 17 beta-HSD, on the other
      hand, catalyze the formation of testosterone from androstenedione in the testis
      and peripheral tissues, respectively. The various types of human 17 beta-HSD,
      because of their tissue-specific expression and substrate specificity, provide
      each peripheral cell with the necessary mechanisms to control the level of
      intracellular androgens and/or estrogens, a new area of hormonal control that we
      call intracrinology.

PMID- 9029732
TI  - The regulation of 3 beta-hydroxysteroid dehydrogenase expression.
AB  - 3 beta-Hydroxysteroid dehydrogenasel delta 5-->4-isomerase (3 beta-HSD) catalyzes
      the formation of delta 4-3-ketosteroids from delta 5-3 beta-hydroxysteroids, an
      obligate step in the biosynthesis not only of androgens and estrogens but also of
      mineralocorticoids and glucocorticoids. The enzyme is expressed in the adrenal
      cortex and in steroidogenic cells of the gonads, consistent with this role.
      However, 3 beta-HSD is also expressed in many other tissues, such as the liver
      and kidney, where its function is not entirely clear. It is established that a
      family of closely related genes encode for 3 beta-HSD. The various 3 beta-HSD
      isoforms are expressed in a tissue-specific manner involving separate mechanisms
      of regulation. The human type I 3 beta-HSD is expressed at high levels in
      syncytial trophoblast and in sebaceous glands, and the type II isoform is almost
      exclusively expressed in the adrenal cortex and gonads. An important feature in
      liver and kidney (at least of hamster, mouse, rabbit, and rat) is the sexual
      dimorphic nature of 3 beta-HSD expression. We briefly review studies on the
      regulation of the human 3 beta-HSD I and II genes in human trophoblast and
      adrenal cortex and extend this to discuss the rat 3 beta-HSD I gene expressed in
      adrenals and gonads. The complexity of 3 beta-HSD expression through multiple
      signaling pathways acting on a multigene family of enzymes may contribute
      importantly to the diverse patterns and locations of steroid hormone
      biosynthesis.

PMID- 9029731
TI  - Steroids, fatty acyl-CoA, and sterols are substrates of 80-kDa multifunctional
      protein.
AB  - The 2.9-kb mRNA of 17 beta-hydroxysteroid dehydrogenase IV codes for an 80-kDa
      (737 amino acids) protein featuring domains that are not present in the other
      human 17 beta-hydroxysteroid dehydrogenases. The N-terminal part reveals
      conserved motifs of the short-chain alcohol dehydrogenase family. The central-
      and C-terminal domains are similar to peroxisomal enzymes for beta-oxidation of
      fatty acids and to sterol carrier protein 2. The 80-kDa protein is N-terminally
      cleaved to a 32-kDa fragment (amino acids 1-323). Both the 80-kDa and the N
      terminal 32-kDa peptides are able to catalyze the dehydrogenation with steroids
      at the C17 position and with 3-hydroxyacyl-CoA. The central part of the 80-kDa
      protein (amino acids 324-596) catalyzes the 2-enoyl-acyl-CoA hydratase reaction
      with high efficiency. The C-terminal part of the 80-kDa protein (amino acids 597
      737) facilitates the transfer of 7-dehydrocholesterol and phosphaidylcholine
      between membranes in vitro. The unique multidomain structure of the 80-kDa
      protein permits the catalysis of several reactions previously thought to be
      performed by complexes of different enzymes.

PMID- 9029733
TI  - The multiple murine 3 beta-hydroxysteroid dehydrogenase isoforms: structure,
      function, and tissue- and developmentally specific expression.
AB  - The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) is essential for the
      biosynthesis of all active steroid hormones. To date five distinct isoforms have
      been identified in the mouse. The different isoforms are indicated by roman
      numerals (I-V) in the chronological order in which they have been isolated. The
      different isoforms are expressed in a tissue- and developmentally specific manner
      and fall into two functionally distinct groups. 3 beta-HSD I, II, and III
      function as NAD(+)-dependent dehydrogenaselisomerases, and IV and V function as
      NADPH-dependent 3-keto steroid reductases. These latter two isoforms, therefore,
      are not involved in the biosynthesis of steroid hormones, but most likely in the
      inactivation of steroid hormones. In the adult mouse 3 beta-HSD I is expressed in
      the classical steroidogenic tissues, the adrenal glands and the gonads. 3 beta
      HSD II and III are expressed in the liver and kidney, with III being the major
      isoform expressed in the adult liver. 3 beta-HSD IV is expressed almost
      exclusively in the kidney of both sexes, and expression of 3 beta-HSD V is
      observed only in the male liver starting late in puberty. In the fetal liver of
      both sexes, 3 beta-HSD I is the major or only isoform expressed at 13.5 days
      postconception and remains the major isoform until the day of birth, after which
      3 beta-HSD III becomes the major isoform. Expression of 3 beta-HSD I in the liver
      decreases after birth and ceases by day 20 postnatally. Thus the liver expresses
      four distinct isoforms of 3 beta-HSD, I, II, III, and V, at different times
      during development. The mouse 3 beta-HSD genes, Hsd3b, have been mapped to a
      small region on mouse chromosome 3. Analysis of two yeast artificial chromosome
      (YAC) libraries identified one clone that contains the entire Hsd3b locus within
      a 1400-kb insert. Hybridization by Southern blot analysis of restriction-enzyme
      digested YAC DNA using an 18-base oligonucleotide that hybridizes without
      mismatch to all known Hsd3b sequences indicates that there are a total of seven
      Hsd3b genes or pseudogenes in the mouse genome. Further analysis of mouse genomic
      DNA by pulse field gel electrophoresis suggests that all of the Hsd3b gene family
      is found within a 400-kb fragment.

PMID- 9029734
TI  - Structure-function relationships of 3 beta-hydroxysteroid dehydrogenase:
      contribution made by the molecular genetics of 3 beta-hydroxysteroid
      dehydrogenase deficiency.
AB  - The transformation of delta 5-3 beta-hydroxysteroids into the corresponding delta
      4-3-keto-steroids is an essential step for the biosynthesis of all classes of
      active steroids: progesterone, mineralocorticoids, glucocorticoids, androgens,
      and estrogens. These steroid hormones play a crucial role in the differentiation,
      development, growth, and physiological function of most human tissues. The
      structures of several cDNAs encoding 3 beta-HSD isoenzymes have been
      characterized in human and several other vertebrate species: human types I and
      II; macaque; bovine; rat types I, II, III, and IV; mouse types I, II, III, IV, V
      and VI; hamster types I, II, and III; and rainbow trout. Their transient
      expression reveals that 3 beta-HSD and delta 5-delta 4-isomerase activities
      reside within a single protein. Distinct approaches have been used for a better
      understanding of the structure-function relationships of these 3 beta-HSD
      enzymes: i) affinity radiolabeling studies of the human type I 3 beta-HSD; ii)
      identification and the functional consequences of the human type-II 3 beta-HSD
      mutations detected in patients with 3 beta-HSD deficiency. Taken together, all of
      these data were examined to determine whether the relationship between the
      genotype and the phenotype of these patients were consistent with in vitro
      mutagenesis studies. 3 beta-HSD deficiency, transmitted in an autosomic recessive
      disorder, is characterized by varying degrees of salt wasting; in genetic males,
      fetal testicular 3 beta-HSD deficiency causes an undervirilized male genitalia
      (male pseudohermaphroditism); females exhibit either normal sexual
      differentiation or mild virilization. All mutations were detected in the type II
      3 beta-HSD gene, which is expressed almost exclusively in the adrenals and
      gonads. No mutation was detected in the type I 3 beta-HSD gene, which is
      expressed in peripheral tissues. The finding of a normal type I 3 beta-HSD gene
      explains the elevated delta 5-steroids and mild virilization of affected girls at
      birth. To date, 24 mutations have been identified in 25 distinct families with 3
      beta-HSD deficiencies. All nonsense and frameshift mutations introducing a
      premature termination codon were associated with the classical salt-losing form.
      The locations of these nonsense mutations suggest that at least the first 318
      amino acids out of 371 are required for 3 beta-HSD activity. The consequences of
      the missense mutations on some domains of the 3 beta-enzyme, such as membrane
      spanning domains, cofactor-binding site, and steroid-binding site, were reviewed.
      The future crystallization of the overexpressed normal and mutant-type II-3 beta
      HSD enzymes should contribute to a better understanding of the structure-function
      relationships of this enzyme, especially for missense mutations located outside
      the putative functional regions.

PMID- 9029735
TI  - The roles of calmodulin, actin, and vimentin in steroid synthesis by adrenal
      cells.
AB  - The rate of steroid synthesis is regulated by the rate of transport of
      cholesterol to mitochondria. The transport process involves two elements of the
      cytoskeleton (microfilaments and intermediate filaments) and Ca2+/ calmodulin.
      Electron microscopy and immunofluorescence reveal that lipid droplets in which
      steroidogenic cholesterol is stored in the cytoplasm are tightly attached to
      vimentin intermediate filaments. Mitochondria are also attached to intermediate
      filaments. Ca2+/calmodulin is known to be essential for the steroidogenic
      response to ACTH and acts to increase transport of cholesterol to mitochondria.
      Ca2+/ calmodulin promotes phosphorylation of two important adrenal proteins:
      vimentin via its protein kinase and myosin light chain via the calmodulin
      dependent light-chain kinase. In permeabilized adrenal cells Ca2+/calmodulin
      causes an ATP-dependent contraction of the cells. Phosphorylation of vimentin is
      known to cause breakdown of intermediate filaments. Electron microscopy reveals
      that actin filaments cross-link intermediate filaments in adrenal cells. It is
      proposed that ACTH has at least two second messengers, Ca2+/calmodulin and cAMP.
      Ca2+/calmodulin causes breakdown of vimentin filaments and activates a
      contractile event dependent on ATP and myosin light chain. These changes
      reorganize the cytoskeleton in such a way as to facilitate the interaction of
      lipid droplets with mitochondria, resulting in transport of cholesterol to these
      organelles and hence increased steroid synthesis.

PMID- 9029736
TI  - 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, a maturation-inducing hormone in fish
      oocytes: mechanisms of synthesis and action.
AB  - Meiotic maturation of fish oocytes is induced by the action of maturation
      inducing hormone (MIH). 17 alpha,20 beta-Dihydroxy-4-pregnen-3-one (17 alpha,20
      beta-DP) was identified as the MIH of several fish species, including salmonid
      fishes. The interaction of two ovarian follicle cell layers, the thecal and
      granulosa cell layers, is required for the synthesis of 17 alpha,20 beta-DP; the
      thecal layer produces 17 alpha-hydroxyprogesterone that is converted to 17
      alpha,20 beta-DP in granulosa cells by the action of 20 beta-hydroxysteroid
      dehydrogenase (20 beta-HSD). The preovulatory surge of LH-like gonadotropin (GTH
      II) is responsible for rapid expression of 20 beta-HSD mRNA transcripts in
      granulosa cells. 17 alpha,20 beta-DP acts via a receptor on the plasma membrane
      of oocytes. A specific 17 alpha,20 beta-DP receptor has been identified and
      characterized from defolliculated oocytes of several fish species. The
      concentrations of 17 alpha,20 beta-DP membrane receptor increase immediately
      prior to oocyte maturation. The pertussis toxin-sensitive inhibitory G protein is
      involved in the signal transduction pathway of 17 alpha,20 beta-DP. The early
      steps following 17 alpha,20 beta-DP action involve the formation of the major
      mediator of this steroid, maturation-promoting factor, which consists of cdc2
      kinase (34 kDa) and cyclin B (46-48 kDa). Immature oocytes contain only monomeric
      35 kDa cdc2 and do not stockpile cyclin B, although immature oocytes contain mRNA
      for cyclin B. 17 alpha,20 beta-DP induces oocytes to synthesize cyclin B, which
      in turn activates preexisting 35 kDa cdc2 through its threonine 161
      phosphorylation by a threonine kinase (M015), producing the 34-kDa active cdc2.
      17 alpha,20 beta-DP-induced oocyte maturation is blocked by cordycepin, a
      polyadenylation inhibitor. Furthermore, cyclin B mRNA was polyadenylated during
      17 alpha,20 beta-DP-induced oocyte maturation. These findings suggest that 17
      alpha,20 beta-DP initiates translation of cyclin B mRNA through cytoplasmic 3'
      poly(A) elongation.

PMID- 9029738
TI  - Apoptosis in steroidogenic cells: structure-function analysis.
AB  - Granulosa cells are the main producers of the female sex steroid hormones,
      progesterone and estradiol, which are responsible for the cyclicity in ovarian
      function. Programmed cell death in the ovary plays a crucial role in limiting the
      number of follicles that can ovulate and thus prevents the development of more
      embryos than can successfully complete pregnancy. Granulosa cell apoptosis is
      regulated by the concerted action of endocrine, paracrine, and autocrine factors.
      These factors lead to the developmental decision of whether the steroidogenic
      cell will luteinize and enter the pathway leading to programmed cell death, or
      whether the life span of the luteinized cell will be prolonged to continue
      secretion of progesterone, which is essential for the maintenance of pregnancy.
      At the level of the individual cell, we find that enhanced steroidogenesis can be
      maintained during the initial steps of apoptosis as long as the steroidogenic
      apparatus remains intact. This can be achieved by a unique mechanism of
      compartmentalization of steroidogenic organelles in the perinuclear region and
      migration of the multicatalytic proteinase, the proteasome, to the apoptotic
      blebs. Reorganization of the actin cytoskeleton during apoptosis may provide an
      efficient barrier between the proteolytic activity and the steroidogenic activity
      in the apoptotic cell. It is suggested that steroidogenesis can be maintained in
      the apoptotic cells as long as the steroidogenic organelles bearing the
      steroidogenic apparatus remain intact.

PMID- 9029739
TI  - Therapeutic drug monitoring databases for postmarketing surveillance of drug-drug
      interactions: evaluation of a paired approach for psychotropic medication.
AB  - The present study investigated the potential of therapeutic drug monitoring data
      to document pharmacokinetic drug interactions with psychotropic medication, both
      in terms of methodology and applicability. It focused on 105 patients exposed to
      one of five agents known for their capacity to induce (phenytoine, phenobarbital,
      and carbamazepine) or to inhibit (thioridazine and levomepromazine) the
      metabolism of psychotropic drugs. These patients were matched by gender, age, and
      monitored psychotropic medication to 105 patients randomly selected from a pool
      of subjects nonexposed to target comedication. Such a paired approach was shown
      to be effective in reducing variability for a majority of substances. Power
      analysis suggested that eight to 10 pairs of exposed and nonexposed patients
      would effectively allow the detection of twofold effects of interacting
      substances. In keeping with the literature, analysis of the ratios of dose
      normalized exposed to nonexposed concentrations indicated that phenothiazine
      comedication led to significantly higher concentrations of desmethylated
      metabolites but not parent compounds, when clomipramine, imipramine, or
      amitriptyline were administered. A similar, as yet undocumented interaction was
      observed for the tetracyclic antidepressant mianserine. In contrast, the present
      study revealed that maprotiline concentrations were increased, but its metabolite
      was largely unaffected by phenothiazine comedication. Increased concentrations
      were also observed for moclobemide, but not citalopram or its metabolite. In
      addition to its long recognized capacity to decrease haloperidol concentrations,
      carbamazepine was shown to induce the metabolism of clopenthixol and possibly
      flupenthixol. The consistency of such a picture substantiates the need to
      consider therapeutic drug monitoring databases as cost-effective and reliable
      tools for postmarketing surveillance.

PMID- 9029737
TI  - Expression of aromatase in the ovary: down-regulation of mRNA by the ovulatory
      luteinizing hormone surge.
AB  - Aromatase (CYP19) mRNA is induced by follicle-stimulating hormone (FSH) in
      granulosa cells of preovulatory follicles and subsequently is rapidly diminished
      as a consequence of the luteinizing hormone (LH) surge. Primary cultures of rat
      granulosa cells were used to identify some of the cellular mechanisms by which
      FSH increases and LH decreases steady-state levels of aromatase mRNA. Induction
      of aromatase mRNA by FSH was increased by cycloheximide but was blocked by alpha
      amanitin and the C-kinase activators gonadotropin-releasing hormone (GnRH) and
      phorbol 12-myristate 13-acetate (PMA). In contrast, the decrease in steady-state
      levels of aromatase mRNA by LH was mimicked by A-kinase (forskolin) and C-kinase
      (PMA or GnRH) activators. The decrease in aromatase mRNA was associated with
      decreased amounts of mRNA and protein for steroidogenic factor-1 (SF-1), a
      nuclear orphan receptor that binds and trans-activates the aromatase promoter,
      and with the A-kinase subunit type II (RII beta), which is required for mediating
      cAMP action in these cells. The down-regulation of aromatase, SF-1, and RII beta
      by each kinase activator and alpha-amanitin was prevented by cycloheximide when
      the drug was added in combination with the activator. If, however, cycloheximide
      was added 2 h after PMA (or LH), the drug did not prevent the rapid loss of mRNA.
      When granulosa cells were transfected with an aromatase CAT transgene, CAT
      activity was stimulated 10- to 20-fold by FSH and forskolin but not by PMA. Taken
      together, these results indicate that the A-kinase but not the C-kinase pathway
      can trans-activate the aromatase gene in immature granulosa cells, whereas the C
      kinase, as well as A-kinase pathways, mimic the LH surge to decrease aromatase
      mRNA in preovulatory cells. By increasing degradation of aromatase mRNA and by
      inhibiting transcription, the LH surge rapidly terminates the granulosa cell
      pattern of gene expression while reprogramming the cells to express genes
      associated with ovulation and luteinization.

PMID- 9029740
TI  - Diffusion characteristics of placental preparations affect the digoxin passage
      across the isolated placental lobule.
AB  - Our aim was to evaluate the isolated placental lobule to study maternofetal
      transplacental digoxin transfer and accumulation in placental tissue in vitro.
      Digoxin passage across the isolated lobule of 10 human placentas was calculated
      from repeated fetal and maternal perfusate samples, and placental tissue digoxin
      concentrations were measured at the end of the experiments. To determine the
      degree of overlap of the fetal and the maternal circulation, the antipyrine
      clearance was used. Digoxin disappearance from the maternal circuit was not
      significantly affected by the degree of overlap. In contrast, the increase of
      digoxin in the fetal compartment was significantly higher in "well-perfused"
      placentas (antipyrine clearance > 1.60 ml/min; n = 5) than in "malperfused"
      placentas (antipyrine clearance < 1.50 ml/min; n = 5) (end-feto to initial
      maternal digoxin ratio 0.44 +/- 0.08 vs. 0.30 +/- 0.08; p < 0.05), whilst the
      accumulation in placental tissue was higher in the latter group (0.45 +/- 0.07
      vs. 0.62 +/- 0.10 ng/mg protein; p < 0.05). We conclude that the isolated
      placental lobule is suitable to quantify transplacental digoxin transfer in
      vitro, but the diffusion characteristics of each preparation have to be
      considered.

PMID- 9029741
TI  - Description of blood pressure changes in patients beginning cyclosporin A
      therapy.
AB  - Cyclosporin A (CyA) is the primary immunosuppressive agent for the prophylaxis of
      rejection episodes in renal, cardiac, liver, and other transplants. Recently, its
      use in autoimmune diseases has been investigated as well. Although several
      studies have produced promising results, nephrotoxicity and hypertension can
      result from CyA treatment, and their development must be understood in order to
      facilitate patient management. This article describes the diastolic blood
      pressure (DBP) responses in two populations of patients during three months of
      CyA therapy. Study A involved psoriasis patients and Study B involved
      postoperative renal transplant patients. The relationship between blood pressure
      and systemic CyA exposure and other covariates was evaluated using linear mixed
      effects modeling. Temporal patterns of blood pressure changes with varying
      duration of CyA exposure were investigated. In Study A, the psoriasis patients
      showed transient exposure-related increases in DBP on CyA. These elevations,
      while statistically significant, were clinically insignificant. In Study B, the
      renal transplant patients showed no CyA-related rises in DBP. In neither study
      was there evidence for a difference in effect on DBP between Sandimmune and
      Neoral, the two formulations of CyA presently approved for marketing by the Food
      and Drug Administration, after differences in CyA exposure were taken into
      account.

PMID- 9029742
TI  - Application of a neural network for gentamicin concentration prediction in a
      general hospital population.
AB  - Neural network (NN) computation is computer modeling based in part on simulation
      of the structure and function of the brain. These modeling techniques have been
      found useful as pattern recognition tools. In the present study, data including
      age, sex, height, weight, serum creatinine concentration, dose, dosing interval,
      and time of measurement were collected from 240 patients with various diseases
      being treated with gentamicin in a general hospital setting. The patient records
      were randomly divided into two sets: a training set of 220 patients used to
      develop relationships between input and output variables (peak and trough plasma
      concentrations) and a testing set (blinded from the NN) of 20 to test the NN. The
      network model was the back-propagation, feed-forward model. Various networks were
      tested, and the most accurate networks for peak and trough (calculated as mean
      percent error, root mean squared error of the testing group, and tau value
      between observed and predicted values) were reported. The results indicate that
      NNs can predict gentamicin serum concentrations accurately from various input
      data over a range of patient ages and renal function and may offer advantages
      over traditional dose prediction methods for gentamicin.

PMID- 9029743
TI  - Population pharmacokinetics of felbamate in children.
AB  - Information about the pharmacokinetics of felbamate in children is limited. Even
      though it is claimed that monitoring of felbamate concentrations is unnecessary,
      many neurologists have requested therapeutic drug monitoring (TDM) for various
      reasons. This study used the NONMEM program to describe the pharmacokinetics and
      the influence of other anticonvulsants on the pharmacokinetics of felbamate.
      Felbamate, carbamazepine (CBZ), phenytoin (PHY), valproate (VPA), and barbiturate
      serum levels were obtained by our TDM service as requested by the clinician. The
      clearance and volume of distribution of felbamate were 41.1 ml/h/kg and 908
      ml/kg, respectively. CBZ and PHY increased the clearance 49 and 40% while VPA
      decreased it 21%. Barbiturate had no significant effect. Clearance also decreased
      with age.

PMID- 9029744
TI  - Comparative serum estradiol profiles from a new once-a-week transdermal estradiol
      patch and a twice-a-week transdermal estradiol patch.
AB  - Two identical open-label, randomized crossover studies were conducted to compare
      serum estradiol profiles from the new 12.5- and 25-cm2 once-a-week adhesive
      patches with those from the 10- and 20-cm2 commercially available twice-a-week
      Estraderm patches when applied as directed during a 1-week patch-wear period.
      Both studies were conducted in healthy postmenopausal women; serum estradiol
      levels were determined by gas chromatography/mass spectroscopy (GC/MS). Although
      both sizes of both patch treatments produced mean serum estradiol levels in the
      therapeutic range, the once-a-week patch provided more constant mean levels,
      avoiding large peak-to-trough fluctuations. As expected, the differences in mean
      serum estradiol concentrations between the two patch treatments occurred during
      the second application of the twice-a-week patch. Based on these results, the
      once-a-week drug in adhesive patch appears to be an acceptable means of hormone
      replacement therapy.

PMID- 9029745
TI  - Increases in plasma concentration of m-chlorophenylpiperazine, but not trazodone,
      with low-dose haloperidol.
AB  - Our previous study suggested that cytochrome P4502D6 (CYP2D6) is involved in the
      metabolism of trazodone and its active metabolite, m-chlorophenylpiperazine (m
      CPP). The purpose of this study was to examine the degrees of increase in plasma
      concentrations of trazodone and m-CPP induced by haloperidol, which is an
      inhibitor of CYP2D6. The subjects were nine depressed inpatients receiving
      trazodone at bedtime (150 mg in seven patients and 300 mg in two) for 2-19 weeks.
      Haloperidol at 4 mg/day was coadministered for 1 week, and blood samplings were
      taken before and after the coadministration. Contrary to our expectation,
      haloperidol did not significantly increase the mean plasma trazodone
      concentration (810 +/- 382 vs. 856 +/- 357 ng/ml). However, haloperidol
      significantly increased (p < 0.01) the mean plasma m-CPP concentration (78 +/- 31
      vs. 92 +/- 34 ng/ml).

PMID- 9029746
TI  - Effect of activated charcoal on the pharmacokinetics of pholcodine, with special
      reference to delayed charcoal ingestion.
AB  - We conducted a randomized study with four parallel groups to investigate the
      effect of single and multiple doses of activated charcoal on the absorption and
      elimination of pholcodine administered in a cough syrup. The first group received
      100 mg of pholcodine on an empty stomach with water only (control); the second
      group took 25 g of activated charcoal immediately after pholcodine; the third
      group received 25 g of activated charcoal 2 h and the fourth group 5 h after
      ingestion of the 100-mg dose of pholcodine. In addition, the fourth group
      received multiple doses (10 g each) of charcoal every 12 h for 84 h. Blood
      samples were collected for 96 h and urine for 72 h. Pholcodine concentrations
      were measured by high-performance liquid chromatography. A significant reduction
      in absorption was found when charcoal was administered immediately after
      pholcodine; the AUC0-96h was reduced by 91% (p < 0.0005), the Cmax by 77% (p <
      0.0005), and the amount of pholcodine excreted into urine by 85% (p < 0.0005).
      When charcoal was administered 2 h after pholcodine, the AUC0-96h was reduced by
      26% (p = 0.002), the Cmax by 23% (p = NS), and the urinary excretion by 28% (p =
      0.004). When administered 5 h after pholcodine, charcoal produced only a 17%
      reduction in the AUC0-96h (p = 0.06), but reduced the further absorption of
      pholcodine still present in the gastrointestinal tract at the time of charcoal
      administration, as measured by AUC5-96h (p = 0.006). Repeated administration of
      charcoal failed to accelerate the elimination of pholcodine. We conclude that
      activated charcoal is effective in preventing the absorption of pholcodine, and
      its administration can be beneficial even several hours after pholcodine
      ingestion.

PMID- 9029748
TI  - Griseofulvin and fluvoxamine interactions with the metabolism of theophylline.
AB  - Theophylline is predominantly metabolized by cytochrome P4501A2 (CYP1A2). A
      possible interaction between griseofulvin and theophylline was reported to our
      laboratory, which led us to form the hypothesis that griseofulvin induces the
      metabolism of theophylline. One purpose of this study was to investigate this
      hypothesis. The study was carried out as a randomized crossover study of 12
      healthy volunteers. In period A of the study, each volunteer received a single
      dose of 300 mg theophylline ethylenediamine orally. In period B, the subjects
      took fluvoxamine, 50 mg for 1 day and 100 mg for 6 days, and on day 4, the
      subjects ingested 300 mg theophylline ethylenediamine. Fluvoxamine is a potent
      inhibitor of CYP1A2, and period B was included as a positive control. In period
      C, the subjects took 500 mg griseofulvin for 9 days; on day 8 the subjects again
      ingested 300 mg theophylline ethylenediamine. Theophylline and its metabolites (1
      methyluric acid [IMU], 3-methylxanthine [3MX], and 1,3-dimethyluric acid [13DMU])
      in plasma and urine were assayed by high-performance liquid chromatography.
      During fluvoxamine intake, the median of the total clearance of theophylline
      decreased from 80 ml/min to 24 ml/min, and the half-life increased from 6.6 to 22
      h. The partial formation clearances of the metabolites decreased from 17 to 1.7
      ml/min, from 8.9 to 0.9 ml/min, and from 21 to 6.8 ml/min for 1MU, 3MX, and
      13DMU, respectively. The results confirm that assessment of theophylline
      metabolism indeed serves as a biomarker for CYP1A2. During griseofulvin
      ingestion, the median of the total and partial clearances of theophylline were 84
      ml/min, 22 ml/min (1MU), 9.4 ml/min (3MX), and 25 ml/min (13DMU). The half-life
      decreased significantly from 6.6 to 5.7 h. The increase in partial formation
      clearances of 1MU and 13DMU, but not of 3MX, were statistically significant. The
      increase in the total clearance reached only borderline significance. In four
      subjects a marked induction was seen for all pharmacokinetic parameters,
      suggesting that the susceptibility to induction is more pronounced in some
      subjects. This susceptibility could theoretically be explained by a polymorphism
      in the inducibility of the gene coding for the CYP1A2 enzyme.

PMID- 9029747
TI  - Therapy for neurocysticercosis: pharmacokinetic interaction of albendazole
      sulfoxide with dexamethasone.
AB  - Albendazole is considered the drug of choice for neurocysticercosis. It is
      frequently used in combination with dexamethasone to prevent the acute
      inflammatory reaction due to cysticercal death. It has been reported that
      dexamethasone increases the plasma level of albendazole sulfoxide, the active
      metabolite of albendazole. The pharmacokinetic interaction of albendazole
      sulfoxide with dexamethasone, associated or not with cimetidine, was investigated
      in 24 patients with active intraparenchymal brain cysticercosis. Eight of these
      patients received albendazole alone, eight received it in combination with
      dexamethasone, and eight received it in combination with both dexamethasone and
      cimetidine. The pharmacokinetic parameters maximum plasma concentration, time to
      maximum plasma concentration, absorption half-life, and absorption rate constant
      did not differ between groups, suggesting that the formation of albendazole
      sulfoxide was not altered by the administration of dexamethasone, combined or not
      with cimetidine. There were significant differences, however, in the parameters
      plasma concentration-time curve, oral clearance, elimination half-life, and
      elimination rate constant, suggesting that dexamethasone, combined or not with
      cimetidine, decreases the rate of elimination of albendazole sulfoxide.

PMID- 9029749
TI  - Pharmacokinetics of high-dose thiopental in pediatric patients with increased
      intracranial pressure.
AB  - This study was conducted on 10 pediatric patients in whom intracranial
      hypertension stemming from head injury was reduced by high-dose thiopental
      administered for a prolonged period. All children showed a favorable recovery of
      their neurological functions. The total dose normalized to body weight averaged
      335 +/- 135 mg/kg, and the mean treatment duration was 93.0 +/- 37.1 h. Data
      analysis was modeled for each patient to cover all the doses on the whole plasma
      thiopental concentration-time curve, according to a one-compartment open model. A
      better fit was obtained using a linear model rather than a Michaelis-Menten
      elimination model. Model selection was guided by evaluation of the minimum
      objective function, the weighted residuals, and the Akaike criterion. Thiopental
      pharmacokinetic parameters in pediatric patients were compared with those
      determined in an adult control group with similar total doses and durations of
      treatment. No significant difference was found between the two groups in spite of
      a 33% decrease of the elimination half-life in children (11.7 +/- 5.7 h) compared
      with adults (17.5 +/- 9.03 h). The mean values obtained were 2.42 and 2.19
      ml/min/kg for total clearance and 2.18 and 2.90 L/kg for Vd in pediatric and
      adult groups, respectively. The linear regression of pharmacokinetic parameters
      in terms of age was not significant. When high doses of thiopental were
      administered over a prolonged period, the pharmacokinetic parameters computed for
      pediatric patients did not differ from those obtained in adults.

PMID- 9029750
TI  - Status epilepticus associated with the combination of valproic acid and
      clomipramine.
AB  - An epileptic patient well controlled on valproic acid (VPA) developed a prolonged
      episode of status epilepticus 12 days after initiation of 75 mg of clomipramine
      (CMI) to treat depression. Serum level of VPA in the emergency room was unchanged
      from her previous levels; serum level of CMI was very elevated despite the
      relatively small dose of CMI. A pharmacokinetic interaction between VPA, an
      enzyme inhibitor, and CMI has not been described but seemed to have occurred in
      this patient. Decreased metabolism of CMI and its metabolites, increased free CMI
      fraction, and precipitation of a nonlinear saturation kinetic state has been
      described when CMI was used concomitantly with other highly protein-bound, enzyme
      inhibiting compounds. This case provides reasonable evidence that the combination
      of VPA and CMI may result in elevation of levels of CMI and possibly of its
      metabolites and may precipitate seizures in patients with an underlying
      predisposition. The elevated serum level of CMI at the time of the seizures,
      despite the relatively small oral dose of the drug, suggests that VPA may have
      inhibited its metabolism and/or elimination.

PMID- 9029751
TI  - Comparison of a fluorescence polarization immunoassay of netilmicin in plasma,
      peritoneal dialysate, and urine with a high-performance liquid chromatographic
      method.
AB  - The quantitative analysis of netilmicin in plasma, peritoneal dialysate, and
      urine using the fluorescence polarization immunoassay (FPIA) of the Abbott TDx
      system is compared with the modified high-performance liquid chromatography
      (HPLC) method of Peng et al., which was chosen as a reference. Using the least
      square method, we found that the results of the FPIA (y) correlated well with
      those obtained with HPLC (x). The three regression equations for the plasma,
      peritoneal dialysate, and urine samples, respectively, were y = 0.71x + 0.44 with
      r = 0.88 and n = 45; y = 0.94x + 1.22 with r = 0.93 and n = 95; and y = 0.92x +
      0.70 with r = 0.93 and n = 61. The corresponding mean errors (FPIA-HPLC) with
      their 95% confidence intervals were -0.19 (-0.38 to -0.02), 0.69 (-0.42 to 1.81),
      and -0.13 (-1.13 to 0.87) microgram/ml. According to results of the Wilcoxon
      matched-pairs signed-ranks test, these errors did not represent a significant
      bias. The FPIA is thus suitable for analyzing netilmicin in the three biological
      fluids studied except when dialysate is contaminated with Amuchina. In this case,
      HPLC should be used.

PMID- 9029752
TI  - A limited sampling method for the estimation of vigabatrin maximum plasma
      concentration and area under the curve.
AB  - A limited sampling model (LSM) was developed to estimate the area under the curve
      (AUC) and maximum plasma concentration (Cmax) for a 1-g oral dose of vigabatrin.
      The model was developed using the data from 10 healthy subjects and one time
      point. The following equations describe the model for AUC and Cmax:
      AUC(predicted) = 5.4 x C3h + 70 and Cmax(predicted) = 0.18 x AUC(0-infinity) +
      9.4. The model was validated in 49 subjects who orally received 1-g vigabatrin.
      This LSM was also used to predict AUC and Cmax volunteers who received 2- and 4-g
      vigabatrin doses and in renal failure patients who were given a 0.75-g dose. The
      model provided good estimates of both AUC and Cmax in all groups of subjects
      except renal dysfunction patients. The method described here may be used to
      estimate AUC and Cmax of vigabatrin without detailed pharmacokinetic studies.

PMID- 9029753
TI  - Ultrafiltration using the Amicon MPS-1 for assessing methadone plasma protein
      binding.
AB  - The percent of protein-free and protein-bound methadone were separated in
      methadone-spiked bank and artificial plasma, and in plasma samples taken from
      methadone-maintained patients using the Amicon MPS-1 ultrafiltration device.
      Following the separation procedure, protein-bound and protein-free methadone were
      extracted from the protein-bound and free fractions, and their respective
      concentrations were determined by gas chromatography and nitrogen-phosphorus
      detection. Eighty-five patient samples from 38 men and 10 women receiving
      methadone maintenance were collected and subjected to the ultrafiltration
      methodology. Two independent procedures demonstrated that, following the
      ultrafiltration process, no proteins were measurable in the filtrate. In
      addition, the ultrafiltration process was found to function independently of the
      concentration of methadone and the volume of sample, assuming the amount filtered
      never exceeded 40% of the original volume. In the patient samples, the %-free
      methadone varied sixfold across all patients. Female patients were found to have
      a mean +/- SD %-free methadone of 11.9 +/- 3.8% vs. 10.1 +/- 3.4% for men.
      Pearson correlation values suggest that steady-state protein-free methadone
      levels (r = 0.521) and total methadone levels (r = 0.491) rise as methadone dose
      is increased. Corresponding to these results, free methadone levels are highly
      correlated with total methadone levels (Pearson r = 0.85). The Amicon MPS-1
      ultrafiltration device appears to be a reliable and relatively easy system to use
      for separating protein-free from protein-bound methadone, though further study is
      required to clarify the clinical applications of free methadone levels.

PMID- 9029754
TI  - A highly sensitive enzyme-linked immunosorbent assay for the determination of
      tacrolimus in atopic dermatitis patients.
AB  - A highly sensitive enzyme-linked immunosorbent assay method has been developed
      for the determination of tacrolimus in human blood samples. The assay is a
      modification of the previously published assay with improved sensitivity.
      Following extraction of tacrolimus with methanol and sulfosalicylic acid, the
      samples are incubated for 2 h at room temperature on a Nunc Maxisorb plate that
      has been treated for nonspecific binding by precoating with polyclonal antibody.
      The analysis of human blood following the standard addition of tacrolimus (0.02
      5.0 ng/ml) demonstrated excellent precision and accuracy over a 6-day period. The
      interday and intraday co-efficients of variation were 6.0-28.9 and 3.9-15.2%,
      respectively. The limit of quantitation was 0.05 ng/ml. The method was used to
      quantitate blood concentration of tacrolimus in patients following the
      administration of tacrolimus ointment.

PMID- 9029755
TI  - Simultaneous determination of phenytoin and carbamazepine in human hair by high
      performance liquid chromatography.
AB  - Drug detection in human hair has been regarded as a potentially useful technique
      for therapeutic drug monitoring and for the assessment of therapeutic compliance.
      An isocratic high-performance liquid chromatography (HPLC) assay for the
      simultaneous measurement of phenytoin and carbamazepine in human hair was used to
      assess therapeutic compliance in a population of patients with epilepsy. After
      alkaline digestion, phenytoin and carbamazepine were separated on a reverse-phase
      column by using a mobile phase of acetonitrile/methanol/water (9:37:54) and
      monitored at a wavelength of 214 nm with methylphenyl-5-phenylhydantoin as
      internal standard. The assay was linear in the range from 0 to 66.66 ng/mg hair,
      and recoveries of both drugs at concentrations of 8.33, 33.3, and 66.66 ng/mg
      hair from the hair matrix ranged from 91.2 to 104.0%. Inter- and intraassay
      coefficients of variation for both drugs (assessed at three concentrations in the
      calibration range) were < 10%. The limits of detection for phenytoin and
      carbamazepine were 2.0 and 1.33 ng/mg hair, respectively.

PMID- 9029756
TI  - Salivary measurement of deferiprone concentrations and correlation with serum
      levels.
AB  - Deferiprone (L1) is the first clinically available oral iron chelator and it has
      been proven to be effective for the treatment of transfusional iron overload in
      thalassemic patients. Because many of these patients have impaired compliance
      with their medications, effective means of continuous monitoring of compliance
      are crucial. Saliva drug monitoring has the potential advantage of an easy,
      noninvasive approach, assuming that it represents serum levels. However, drugs
      have variable correlations between saliva and serum concentration. We compared
      serum and saliva levels of L1 at various time points after ingestion of a 75
      mg/kg/day dose in nine thalassemic patients. A highly significant correlation
      between serum-free L1 and saliva levels (r = 0.97, p = 0.0003) was found.
      Pharmacokinetic profiles were similar using serum and saliva monitoring. We
      conclude that saliva can be substituted for serum in monitoring L1 levels.

PMID- 9029757
TI  - False-positive EMIT II opiates from ofloxacin.
AB  - The cross-reactivities of four quinolone antibiotics--ofloxacin, norfloxacin,
      ciprofloxacin, and nalidixic acid--toward the EMIT II Opiates enzyme immunoassay
      were examined. Drug-free urine was spiked with the individual drugs up to 5,000
      mg/L. Only ofloxacin showed potential for causing a false-positive opiates
      immunoassay screening result (apparent morphine > 300 micrograms/L). The method
      produced a positive opiate result at an ofloxacin concentration of 200 mg/L, a
      0.16% cross-reactivity. Three hospitalized patients taking therapeutic doses of
      ofloxacin all gave false-positive EMIT II Opiates urine screening results. Three
      patients taking norfloxacin and three patients taking ciprofloxacin gave true
      negative urine screening results. False-positive results were also obtained from
      the urines of two volunteers who each consumed a single 400-mg ofloxacin pill.

PMID- 9029758
TI  - A rapid and specific assay for the determination of lamotrigine in human plasma
      by normal-phase HPLC.
AB  - A rapid and specific high-performance liquid chromatography assay of lamotrigine
      in human plasma is described. Lamotrigine is extracted with dichloromethane from
      buffered plasma to which an internal standard has been added. The solvent is
      directly injected into a 250 x 4.6-mm Spherisorb Silica column and the drug is
      eluted by using a mixture of methanol, n-heptane, dichloromethane, and 28-30%
      ammonium hydroxide (20:40:40:0.3 vol/vol) at a flow rate of 1 ml/min. The eluates
      are detected at 240 nm. The assay requires 250 microliters of sample, and
      concentrations as low as 0.4 microgram/ml can be measured accurately. The method
      is linear in the range of 0.4-16 micrograms/ml, with a mean coefficient of
      correlation (r) > or = 0.997. Within- and between-day relative standard
      deviations at three different concentration levels (1, 4, and 8 micrograms/ml)
      are < or = 8.6%.

PMID- 9029759
TI  - A simple, automated, nonextraction assay for serum digoxin using particle
      enhanced immunoassay.
AB  - We have adapted a latex particle-enhanced immunoassay for serum digoxin to a
      centrifugal analyser. A 4-microliter serum sample (without pretreatment) inhibits
      the monoclonal antibody induced aggregation of digoxin-coated latex particles.
      The total assay time is 10 min and mean analytical recoveries were 98.1%. Intra
      and interassay precision were < 4.2 and < 15.0%, respectively. Method comparison
      with an established fluorescence polarisation immunoassay (FPIA) gave R = 0.97,
      and a Deming regression analysis of particle-enhanced turbidimetric inhibition
      immunoassay (PETINIA) = FPIA x 0.78 + 0.007 microgram/L (n = 91). There was no
      evidence of significant interference from digoxin-like immunoreactive compounds
      in patients with chronic renal failure. This assay can be adapted to most
      photometric analysers used in routine laboratories and is a significant advance
      in the sensitivity of latex particle-enhanced immunoassays in a serum matrix.

PMID- 9029760
TI  - Determination of rapamycin in whole blood by HPLC.
AB  - Sirolimus (rapamycin, RAPA) is a natural fermentation product (macrolide
      antibiotic) that has demonstrated potent immunosuppressive activity. A reverse
      phase high-performance liquid chromatographic (HPLC) method is described for
      analysis of the drug in whole blood. The samples are purified by using liquid
      liquid extraction with butyl chloride/diethyl ether combined with reversed-phase
      solid-phase extraction. RAPA and internal standard were traced by UV-detection at
      278 nm. Linear calibration curves with correlation coefficients > 0.999 were
      obtained (range, 1-50 ng/ml). Minimum detectable concentration was approximately
      0.4 ng/ml and recovery approximately 45% for both RAPA and internal standard.
      Coefficient of variation (day to day) was 9.8% at 5 ng/ml (n = 6) and 5.6% at 40
      ng/ml (n = 6). The chromatography requires < 10 min per sample. The assay has
      proved to be free of interference peaks from cyclosporine or tacrolimus. The
      method has been used to determine the whole blood concentrations in samples from
      healthy volunteers and renal transplant recipients receiving single and multiple
      doses of oral rapamycin.

PMID- 9029761
TI  - Interference with vancomycin fluorescence polarisation immunoassay in a
      nonuraemic patient.
AB  - Commercially available immunoassays for vancomycin have been reported to
      overestimate serum vancomycin concentrations by varying degrees in patients with
      renal impairment, particularly those on peritoneal dialysis, by interference with
      crystalline degradation product-1 (CDP-1). To date this interference has not been
      reported in any other patient population. This report describes vancomycin
      fluorescence polarisation immunoassay (FPIA) interference in a patient with only
      mildly impaired renal function. At this time it is not possible to confirm that
      the interference was caused by CDP-1.

PMID- 9029762
TI  - Interaction between tacrolimus and erythromycin.
AB  - A 40-year-old Asian man, 6 months post renal transplant and receiving tacrolimus
      therapy, presented to the emergency department with a complaint of sudden-onset
      left eye pain with blurred vision, headache on the left side, and nausea and
      vomiting. On being admitted, the patient was intubated for respiratory
      depression, and erythromycin was initiated for suspected atypical pneumonia.
      Tacrolimus concentrations (whole blood) drawn on the 3rd day of hospitalization
      were reported to be > 60.0 ng/ml. Before hospitalization, tacrolimus
      concentrations were reported to be 9.8 ng/ml on a maintenance dose of 7 mg twice
      daily. Six days after discontinuation of erythromycin and a decrease in
      tacrolimus dose, the concentration decreased to 11.5 ng/ml and the original dose
      of tacrolimus was restarted. It is recommended that concurrent administration of
      erythromycin and tacrolimus be avoided. However, if concomitant therapy is
      necessary, tacrolimus concentrations, serum creatinine, blood urea nitrogen, and
      urine output should be monitored.

PMID- 9029763
TI  - Ultrastructural pathology of glial brain tumors revisited: a review.
AB  - The ultrastructural pathology of primary brain tumors of glial origin is
      examined. These are divided into two major groups. The first category comprises
      astrocytoma with the variants: fibrillary, protoplasmic, gemistocytic, and
      anaplastic. These are biologically aggressive tumors of a relatively high
      proliferative potential and include a substantial proportion of cases that
      transform into the most malignant secondary glioblastoma. The second category,
      comprised of rather benign tumors of a limited proliferative capacity and a
      reasonable good prognosis, includes such clinico-pathological entities as
      pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant cell
      astrocytoma of tuberous sclerosis. There is no ultrastructural feature, however,
      which makes it possible to discriminate between major subclasses of astrocytes;
      but secondary glioblastoma cells, while still retaining the stigmata of
      neoplastic astrocytes, are characterized by nuclei that seem to be more indented,
      cisterns of the endoplastic reticulum may be distended, and intranuclear
      pseudoinclusions are frequently observed. Primary glioblastoma, which probably
      originates de novo, is characterized by poorly differentiated cells with a
      paucity of subcellular organelles and no obvious features of astrocytic origin.
      Granular cell tumor also belongs to neoplasms of astrocytic lineage and the
      hallmark of this entity is a cell characterized by the presence of numerous
      membrane-bound, electron-dense autophagic vacuoles. Its malignant analogue is the
      granular cell glioblastoma. Two subtypes of granular cell glioblastoma have been
      distinguished. The first is characterized by the presence of numerous granular,
      electron-dense bodies which correspond to autophagic vacuoles. The second type is
      characterized by numerous electron-dense, amorphous masses within cellular
      processes. These electron-dense inclusions are virtually indistinguishable from
      minute Rosenthal fibers. The pilocytic astrocytoma is virtually indistinguishable
      at the ultrastructural level from fibrillary astrocytomas but cells tend to be
      more elongated. Besides Rosenthal fibers, two types of distinctive structures are
      relatively common in pilocytic astrocytomas: eosinophilic hyaline droplets and
      round granular bodies, which are composed of large aggregates of electron-dense
      secondary lysosomes or small electron-dense bodies, respectively. Pleomorphic
      xanthoastrocytoma is characterized by astrocytes surrounded by basal membranes.
      It belongs to a peculiar category of astrocytic "desmoplastic" brain tumors
      occurring in younger patients, the common denominator for which is the presence
      of basal lamina. The last category in this group is subependymal giant cell
      astrocytoma, a tumor of bivalent (glial and neuronal) differentiation, the cells
      of which are characterized by the presence of peculiar crystalloids. The hallmark
      of oligodendroglioma is the presence of concentric arrays of membranes (so-called
      membrane laminations, whorls, or scrolls). A fragment of the cytoplasm
      sequestrated within a particular whorl may contain mitochondria, lysosomes, or
      abundant glycogen granules. Ependymomas are characterized by a florid picture
      dominated by the presence of microlumina, cilia with basal bodies
      (blepharoplasts), microvilli, and long, interdigitating intercellular junctions
      of the zonulae adherentiae type. Ganglioglioma, the last category covered by this
      review, is a mixed glio-neuronal tumor. While glial cells are indistinguishable
      from their counterparts encountered elsewhere (mostly pilocytic astrocytes), the
      ganglion cells are characterized by abundant intracytoplasmic dense-core
      vesicles, absence of intermediate filaments, and numerous microtubules.
      Occasionally a close apposition of ganglion cells and Rosenthal fibers is seen.
      Dense-core vesicles are pleomorphic and ranged in a diameter from small synaptic
      vesicles to large lysosome-like neurosecretory granules.

PMID- 9029764
TI  - Immunocytochemical and immunoelectron microscopical analysis of BCL2 expression
      in thyroid oxyphilic tumors.
AB  - In both human lymphoma and carcinoma, BCL2 expression contributes to the
      neoplastic development by preventing normal turnover due to programmed cell
      death. In thyroid carcinoma it was shown that BCL2 expression is related to cell
      differentiation and appears to be associated with a less aggressive behavior.
      Using immunogold electron microscopy labeling techniques on ultrathin frozen
      sections, the authors undertook an analysis of bcl-2 protein localization in 7
      cases of thyroid tumor with (4 cases) or without (3 cases) oncocytic
      differentiation, which displayed histopathological features, corresponding to
      different degree of aggressiveness. All thyroid tumors and a lymphoblastoid cell
      line overexpressing BCL2 showed a preferential labeling of mitochondrial
      circumference, while the 4 cases with oncocytic differentiation displayed a bcl-2
      protein location, not only on the circumference but also on the cristae of a
      consistent number of mitochondria. These results may indicate a bcl-2 protein
      interaction with intramitochondrial constituents related to the neoplastic
      transformation in oncocytic tumor.

PMID- 9029765
TI  - Ultrastructural and morphometric investigation of human brain capillaries in
      normal and peritumoral tissues.
AB  - Capillaries of peritumoral and normal brain tissues were ultrastructurally and
      morphometrically investigated to evaluate the changes in peritumoral capillaries
      connected with the tumor-associated vasogenic edema. The endothelial cells of
      peritumoral capillaries showed varying thickness, electron-lucent cytoplasm, and
      structurally normal tight junctions. The basal lamina was thickened, rarefied,
      and vacuolated. The pericytes were provided with pinocytotic vesicles and
      phagocytic bodies. The astrocytic glia appeared empty or swollen, with few
      glycogen granules and a disarranged cytoskeleton; well-preserved glia was
      occasionally observed. The brain tissue was slightly edematous. No statistically
      significant differences were observed between normal and peritumoral capillaries
      as regards diameter, wall thickness, endothelial thickness, and endothelial
      vesicle density. Instead, the peritumoral capillaries displayed three times as
      many endothelial surface-connected vesicles, a markedly thicker basal lamina, and
      significantly reduced extension of pericytic and glial investments. The kind and
      severity of the vascular modifications, compared with the slight edematous
      appearance of the nervous tissue, strengthen the hypothesis that peritumoral
      capillaries could be involved in the edema resolution process.

PMID- 9029766
TI  - Richner-Hanhart's syndrome: new ultrastructural observations on skin lesions of
      two cases.
AB  - New ultrastructural observations are described in skin lesions of two brothers
      with Richner-Hanhart's syndrome (RHS). Physical examination of the two patients
      showed painful skin lesions of palms and soles combined with denderitic corneal
      ulceration and mental retardation. The diagnosis of RHS was confirmed
      biochemically with high tyrosine levels in both blood and urine. Examination by
      transmission electron microscopy revealed several abnormal ultrastructural
      changes in the epidermal cells. The horny cells contained heterogeneously,
      electron-dense cytoplasm with many lipid droplets. The granular cell cytoplasm
      contained abundant tonofibrils and keratohyaline granules. The spinous cell
      cytoplasm was vacuolated due to the presence of minute tyrosine crystals, which
      are known to have a lytic effect. The surrounding keratinocytes contained
      multilobed nuclei. The basal epidermal cells appeared normal except for Merkel
      cells, which were severely damaged by vacuolatio, also due to the presence of
      tyrosine crystals. This study showed that high tyrosine levels can induce several
      ultrastructural pathological changes in the epidermal cells, including the skin
      chemoreceptor Merkel cells.

PMID- 9029767
TI  - Unique intracerebral tumor with divergent differentiation in a patient presenting
      as NF2: report of a case with features of astrocytoma, ependymoma, and PNET.
AB  - Patients with neurofibromatosis 2 (NF2) are predisposed to a variety of
      neoplastic and dysplastic lesions, including schwannomas, neurofibromas,
      meningiomas, astrocytomas, and ependymomas, as well as entities such as
      meningioangiomatosis, schwannosis, and hamartomas. This study reports a unique
      intracerebral frontotemporal tumor in a 6-year-old boy with presumed NF2, on the
      basis of bilateral cerebellopontine tumors consistent with acoustic neuromas. The
      intracerebral tumor revealed a variety of histological patterns, including foci
      of primitive neuroectodermal tumor (PNET), low-grade astrocytoma and ependymoma,
      as well as neuroepithelial rests with immature ganglion cells and hamartomatous
      areas. The MIB-1 labeling index ranged from 63% in the foci of PNET to 4-7% in
      other foci. The PNET component revealed immunopositivity for synaptophysin and
      neurofilament and showed cells with delicate intercellular junctions, profiles of
      rough endoplasmic reticulum, mitochondria, and dense core granules, and cell
      processes with microtubules and neurofilaments. The glial and ependymal
      components showed bundles of glial filaments and prominent cell junctions, cilia,
      and microvilli. The hamartomatous component also included aggregates of cells
      with hyaline eosinophilic cytoplasm. By EM these cells contained abundant
      amorphous flocculent material. This constellation of pathologic findings,
      especially the finding of PNET, is unique and not previously reported in the
      setting of NF2.

PMID- 9029768
TI  - Adenosarcoma of the uterus with extensive smooth muscle differentiation:
      ultrastructural study and review of the literature.
AB  - Four cases of Mullerian adenosarcoma were studied by light and electron
      microscopy and immunohistochemistry. All 4 cases showed the histologic
      characteristics of adenosarcoma with benign endometrial glands and a malignant
      stroma. Ultrastructurally, the epithelial component in all cases had the
      appearance of proliferative endometrial glands, and the malignant mesenchymal
      cells showed features of endometrial stroma. A distinct basal lamina separating
      glands from stroma was present. In addition, 2 of the cases showed extensive
      smooth muscle differentiation which was associated with sarcomatous overgrowth.
      The smooth muscle features were confirmed by immunohistochemistry. Multiple
      theories of the histogenesis of this tumor are discussed.

PMID- 9029770
TI  - Case for the panel. When is a spike truly a spike? Brief observations from a
      pediatric renal biopsy population.

PMID- 9029769
TI  - Head and neck fibromyxoid sarcoma: clinicopathological correlation with emphasis
      on peculiar ultrastructural features related to collagen processing.
AB  - A fibromyxoid sarcoma of the jaw of a young patient is described. The tumor
      recurred and was locally aggressive but displayed mostly a low-grade morphology
      with only a few areas showing undifferentiated (high-grade) appearance. An
      isolated lung metastasis was identified 15 years after the original presentation.
      Ultrastructurally, the tumor cells showed features of partial fibroblastic
      differentiation, with abundant and often markedly dilated rough endoplastic
      reticulum cisternae, but also interrupted segments of basal lamina. The cytoplasm
      contained numerous large, spindle-shaped, membrane-bound inclusions of collagen
      that showed a complex triple periodicity. A distinct cell polarity was seen, with
      the nucleus at one end of the cell and the collagenous inclusions at the other.
      All of these features indicate a tumor with significant cytodifferentiation,
      correlating with the relatively protracted clinical course. The intercellular
      space contained mature collagen fibers and scattered aggregates of delicate,
      slender fibers embedded in moderately electron-dense granular matrix
      (fibrillogranular aggregates). The results suggest that based on its morphology
      and clinical presentation this tumor represents an unusual variant in the
      spectrum of fibromyxoid sarcomas.

PMID- 9029771
TI  - Gap junctional vesicles in intimal smooth muscle cells in human atherosclerotic
      arteries.

PMID- 9029772
TI  - Increased emphasis on viruses associated with neoplasia.

PMID- 9029773
TI  - Two-dimensional gel analysis of [35S]methionine labelled and phosphorylated
      proteins present in virions and light particles of herpes simplex virus type 1,
      and detection of potentially new structural proteins.
AB  - Cells infected with herpes simplex virus (HSV) synthesize both infectious viruses
      and non-infectious light particles (L-particles). The latter contain the envelope
      and tegument components of the virions, but lack virus capsid and DNA.
      Electrophoresis in SDS-polyacrylamide gels (SDS-PAGE) has been used extensively
      for analysis of structural proteins in virions and L-particles. Two-dimensional
      (2-D) gel electrophoresis, however has a markedly higher resolution, and in the
      present work we have used this technique to study both [35S]methionine labelled
      and phosphorylated structural proteins in virions and L-particles. Proteins were
      assigned to the tegument or the envelope by the analysis of L-particles.
      Localization of structural proteins was also determined by stepwise
      solubilization in the presence of the neutral detergent NP-40 and NaCl, and by
      isolation of capsids from nuclei of infected cells. Different steps in
      posttranslational modification can be detected by 2-D gel electrophoresis such
      that a single polypeptide may appear as several spots. This was most clearly
      observed for some of the HSV-encoded glycoproteins which were shown to exist in
      multiple forms in the virion. Some polypeptides apparently not identified
      previously were either capsid associated, or localized in the tegument or
      envelope. The degrees of phosphorylation in L-particles and virions are almost
      identical for some proteins, but markedly different for others. Thus,
      glycoprotein E of HSV-1 is for the first time shown to be phosphorylated, and
      most heavily so in virions. The IE VMW)110 protein represents a group of proteins
      which are more phosphorylated in L-particles than in virions. Attempts are made
      to correlate the proteins detected by 2-D analysis with those previously
      separated by SDS-PAGE.

PMID- 9029774
TI  - Assembly of the reovirus outer capsid requires mu 1/sigma 3 interactions which
      are prevented by misfolded sigma 3 protein in temperature-sensitive mutant
      tsG453.
AB  - A temperature-sensitive reovirus mutant, tsG453, whose defect was mapped to major
      outer capsid protein sigma 3, makes core particles but fails to assemble the
      outer capsid around the core at non-permissive temperature. Previous studies that
      made use of electron cryo-microscopy and image reconstructions showed that mu 1,
      the other major outer capsid protein, but not sigma 3, interact extensively with
      the core capsid. Although wild-type sigma 3 and mu 1 interact with each other,
      immunocoprecipitation studies showed that mutant sigma 3 protein was incapable of
      interacting with mu 1 at the non-permissive temperature. In addition,
      restrictively-grown mutant sigma 3 protein could not be precipitated by some
      sigma 3-specific monoclonal antibodies. These observations suggest that in a wild
      type infection, specific sigma 3 and mu 1 interactions result in changes in mu 1
      conformation which are required to allow mu 1/sigma 3 complexes to condense onto
      the core capsid shell during outer capsid assembly, and that sigma 3 in non
      permissive tsG453 infections is misfolded such that it cannot interact with mu 1.

PMID- 9029775
TI  - Temperature sensitive mutants of influenza A virus generated by reverse genetics
      and clustered charged to alanine mutagenesis.
AB  - Temperature sensitive (ts) mutants of influenza A virus have the potential to
      serve as live attenuated (att) virus vaccines. Previously, ts mutants were
      isolated by chemical mutagenesis or arose spontaneously, and most likely
      contained point mutations in one or more genes. While sufficiently attenuated,
      even the most genetically stable of these viruses was found to revert to a more
      virulent form in a seronegative vaccinee. Recently developed technology, however,
      allows the introduction of engineered mutations into the genome of influenza A
      and B viruses, permitting the rational design of attenuated mutants with the
      potential for increased genetic stability. To accomplish this goal, we have
      introduced ts mutations into the PB2 gene of A/Los Angeles/2/87 (H3N2) and
      rescued the mutated genes into infectious viruses. We have used clustered charged
      to alanine mutagenesis (substitution of alanine for charged amino acid residues
      which are present in clusters) of the PB2 gene to generate novel ts mutants.
      Viruses containing such ts PB2 genes were attenuated in mice and ferrets. This
      approach has thus yielded several vaccine candidates with ts and attenuated
      characteristics in animal models. Combination of these mutations with each other
      or with other ts mutations may lead to a high level of genetic stability.

PMID- 9029777
TI  - Characterization of canine herpesvirus glycoprotein C expressed by a recombinant
      baculovirus in insect cells.
AB  - The gene encoding the canine herpesvirus (CHV) glycoprotein C (gC) homologue has
      been identified by sequence homology analyses with other well studied
      herpesviruses. Previously, we have identified three CHV glycoproteins, gp145/112,
      gp80 and gp47 using a panel of monoclonal antibodies (MAbs). To determine which
      CHV glycoprotein corresponds to gC, a recombinant baculovirus which contains the
      putative CHV gC structural gene under the baculovirus polyhedrin promoter was
      constructed. The recombinant baculovirus expressed gC-related polypeptides (44-62
      kDa), which reacted only with MAbs against CHV gp80, indicating that the
      previously identified CHV gp80 is the translation product of the gC gene. The
      baculovirus expressed gC was glycosylated and transported to the surface of
      infected cells. At least seven neutralizing epitopes were conserved on the gC
      produced in insect cells. It was found that the recombinant baculovirus infected
      cells adsorbed murine erythrocytes as is the case for CHV-infected cells. The
      hemadsorption activity was inhibited by heparin, indicating that the CHV gC binds
      to heparan sulfate on the surface of murine erythrocytes. Mice immunized with the
      recombinant gC produced strong neutralizing antibodies. Our results suggest that
      CHV gC produced in insect cells may be useful as a subunit vaccine to control CHV
      infections.

PMID- 9029776
TI  - Use of persistent infections with vaccinia virus recombinants to introduce
      alterations in foreign proteins: an application to HIV-1 env protein.
AB  - With the aim of generating a virus-cell system to introduce alterations in
      proteins of interest--which may be of use in studies of their biological
      functions--we established a persistent infection on a B-lymphoma cell line
      (A20.2J) with vaccinia virus (VV) recombinants. As a model, we used a vaccinia
      virus recombinant expressing the human immunodeficiency virus HIV-1 env gene. In
      this unique virus-cell system, we found that it is possible to introduce several
      structural and functional alterations in the env protein with passage numbers.
      From passage 10-20, two new env products emerged: an uncleaved gp160 and a
      glycoprotein fragment of 110 kDa. The uncleaved gp160 exhibit interesting
      properties as an immunogen. This protein forms stable oligomers, is not released
      from the cells, cannot fuse CD4+ presenting HeLa cells and activates a stronger
      cellular immune response than the parental cleaved env. In contrast, the 110 kDa
      product is a poor immunogen, since it lacks the gp41 domain, cannot form
      oligomers, accumulates intracellularly and cannot fuse CD4+ cells. In the
      persistently infected cells we have also found alterations in another
      heterologous protein-beta-galactosidase-a gene inserted in the same locus of VV
      as the env gene. This alteration resulted in a truncation of the (beta
      galactosidase protein from 125 kDa to about 70 kDa. A similar size truncation of
      env and of beta-galactosidase was observed in many of the isolated VV
      recombinants.

PMID- 9029778
TI  - A dual role for endothelial cells in cytomegalovirus infection? A study of
      cytomegalovirus infection in a series of rat endothelial cell lines.
AB  - Several clinical findings point to the involvement of microvascular endothelial
      cells in cytomegalovirus-related pathology. In this study the interactions of
      cytomegalovirus (CMV) with microvascular endothelial cells was investigated in an
      in vitro rat model. A series of rat endothelial cell lines, considered
      representative for the heterogeneity of heart microvascular endothelium in vivo,
      were infected with rat CMV (RCMV). The course of infection and production of
      infectious virus were examined using immunofluorescence staining and plaque
      titration assays, and was compared with infection of fully permissive rat
      fibroblasts. These endothelial cell lines displayed differences in susceptibility
      to CMV infection. Two endothelial cell lines (RHEC 50 and 191) were practically
      non-permissive, while four endothelial cell lines (RHEC 3, 10, 11 and 116) were
      partly permissive for CMV infection. In contrast to CMV infection in fibroblasts,
      only limited infection of the permissive endothelial cell lines was observed
      without spreading of CMV infection through the monolayer, although infectious
      virus was produced. Detachment of infected endothelial cells and recovery of the
      monolayer with time was observed. The detached endothelial cells were able to
      transmit CMV infection to fibroblast monolayers, but not to endothelial
      monolayers. Our in vitro results demonstrate differences in permissiveness for
      RCMV between the series of rat endothelial cell lines, which is suggestive for
      endothelial heterogeneity to CMV infection in vivo. Our findings indicate that
      endothelial cells are relatively resistant to CMV infection and that, upon
      infection, the endothelial monolayer may dispose of the virus via detachment of
      the infected cells. This points to a dual role for the endothelium in CMV
      infection in vivo: a barrier for CMV infection (by the endothelial monolayer) on
      the one hand and spreading of CMV infection (by detached infected cells) on the
      other hand.

PMID- 9029779
TI  - Expression and properties of feline herpesvirus type 1 gD (hemagglutinin) by a
      recombinant baculovirus.
AB  - We constructed a recombinant baculovirus expressing feline herpesvirus type I
      (FHV-1) gD in insect cells (Sf9 cells). The expressed product was identified as
      FHV-1 gD by a panel of monoclonal antibodies specific for the FHV-1 gD, and had
      an apparent molecular mass of approximately 49 kDa, which was less than that of
      the authentic FHV-1 gD. When the FHV-1 gD protein were expressed in Sf9 cells and
      CRFK cells in the presence of tunicamycin, the FHV-1 gD exhibited a molecular
      mass of 41 kDa. It was shown that the gD protein was transported to the surface
      of recombinant virus-infected Sf9 cells when examined by membrane
      immunofluorescence analysis, and that the gD expressed on the surface of Sf9
      cells adsorbed feline erythrocytes. Mice inoculated with a lysate of Sf9 cells
      expressing FHV-1 gD induced antibodies with virus-neutralizing and
      hemagglutination-inhibition activities. Therefore, the expressed gD appears to be
      biologically authentic. These data suggested that recombinant FHV-1 gD produced
      in Sf9 cells may be a useful immunogen as a feline vaccine.

PMID- 9029781
TI  - GB virus C/hepatitis G virus infection among Japanese patients with chronic liver
      diseases and blood donors.
AB  - Recently, a novel hepatitis virus, GB virus C/hepatitis G virus (GBV-C/HGV), has
      been isolated. To elucidate the seroprevalence of chronic GBV-C/HGV infection in
      Japan and the phylogenetic relationship between Japanese strains and the strains
      previously reported, serum GBV-C/HGV RNA was detected by reverse transcription
      polymerase chain reaction (RT-PCR) in 203 patients with chronic liver diseases
      and 200 samples of voluntary blood donors. RT-PCR was performed with primers
      derived from the 5'-untranslated region which were conserved between GBV-C and
      HGV and distant from other flaviviruses including hepatitis C virus (HCV). The
      nucleotide sequences were determined by the dideoxy chain termination method. The
      phylogenetic analysis was performed by the neighbor-joining method. In 10 (4.7%)
      of 203 patients with chronic liver diseases and in 1 (0.5%) of 200 blood donor
      samples, serum GBV-C/HGV RNA was detected. Of 10 patients, 9 patients were
      positive for anti-HCV and negative for HBsAg, and 1 patient was positive for
      HBsAg and negative for anti-HCV. The phylogenetic analysis indicated that there
      were three major groups which were group 1 (GBV-C), group 2 (HGV), and group 3 (a
      group of Japanese strains). These data indicated that (1) there was a low
      prevalence of GBV-C/HGV infection in Japanese patients with chronic liver
      diseases, (2) a high proportion of patients with GBV-C/HGV infection had chronic
      HCV infection however, and (3) there were at least three groups in strains of GBV
      C/HGV.

PMID- 9029780
TI  - Sequence analysis of hepatitis GB virus C (GBV-C) isolates from 14 patients.
AB  - In 1995, a new human hepatitis virus belonging to the family Flaviviridae was
      described and designated hepatitis GBV-C. To investigate variations within the
      genome of GBV-C and to study the relationship of GBV-C to GBV-A/B or hepatitis C
      virus (HCV), we established a detection system using reverse transcriptase
      polymerase chain reaction (RT-PCR) of the putative helicase region (NS3). So far,
      isolates derived from 14 different GBV-C-positive sera were analyzed (GBV-C/S3
      36), showing 80.1-89.4% (mean: 85%) identical nucleotides. The deduced amino acid
      sequences revealed 97.3% homology. Nucleotide sequences of GBV-C/S3-36 revealed
      about 60% identity to GBV-A as well as to HCV, but only 56% identity to GBV-B.
      Amino acid sequences revealed 73.4 and 68.6% similarity to GBV-A and GBV-B,
      respectively, but a slightly higher percentage of 78.5% to HCV sequences. Thus,
      according to the putative GBV-C helicase sequence, a subtyping of GBV-C into
      different genotypes may be necessary.

PMID- 9029782
TI  - Expression of parvovirus LuIII NS1 from a Sindbis replicon for production of
      LuIII-luciferase transducing virus.
AB  - In order to develop an alternative packaging system for recombinant parvoviruses,
      the gene for the major nonstructural protein (NS1) of parvovirus LuIII was
      inserted into a Sindbis replicon vector. Cells infected with recombinant SinNS1
      virus produced NS1 RNA from the Sindbis 26S promoter and expressed NS1 protein
      which was able to transactivate a parvovirus P38 promoter. Co-transfections of
      Sindbis-NS1 RNA together with a packageable LuIII transducing genome and a coat
      protein expression plasmid generated detectable levels of LuIII-luciferase
      transducing virus. These levels could be increased by a capsid expression plasmid
      that was also capable of expressing NS2. These results show that a multi
      functional parvovirus protein expressed from a Sindbis RNA molecule can be used
      to produce recombinant parvoviruses.

PMID- 9029783
TI  - Evidence for the association of Nef protein with HIV-2 virions.
AB  - HIV-Nef protein supports viral infectivity prior to proviral integration. This
      requires Nef to be present before the expression of viral genes and suggests its
      delivery as part of the virion. We report here that the Nef proteins of HIV-2-HOM
      and HIV-2-ROD are associated with the virion. After the separation of pelleted
      virus in a 20-60% sucrose density gradient, both proteins cosedimented with the
      virion-associated reverse transcriptase (RT) activity at a density characteristic
      of retroviral particles. Whereas Nef-2-ROD was present in the virion only as the
      full-length protein, HIV-2-HOM appeared as 32 and 35 kDa isoforms. The smaller
      isoform is identical in molecular weight to the protein expected from proteolytic
      cleavage of full-length Nef-2-HOM by the virion-based protease. Virion
      association of Nef helps to explain the recently redefined biological function of
      this regulatory protein.

PMID- 9029784
TI  - Cooperation between transmissible gastroenteritis coronavirus (TGEV) structural
      proteins in the in vitro induction of virus-specific antibodies.
AB  - Following infection of haplotype defined NIH-miniswine with virulent
      transmissible gastroenteritis coronavirus (TGEV), isolated mesenteric lymph node
      CD4+ T-cells mounted a specific proliferative response against infectious or
      inactivated purified virus in secondary in vitro stimulation. A specific, dose
      dependent response to the three major recombinant viral proteins: spike (S),
      membrane (M), and nucleoprotein (N), purified by affinity chromatography, was
      characterized. Induction of in vitro antibody synthesis was analyzed. The
      purified recombinant viral proteins induced the in vitro synthesis of
      neutralizing TGEV-specific antibodies when porcine TGEV-immune cells were
      stimulated with each of the combinations made with two of the major structural
      proteins: S + N, S + M, and to a minor extent with M + N, but not by the
      individual proteins. S-protein was dissociated from purified virus using NP-40
      detergent and then micellar S-protein oligomers (S-rosettes) were formed by
      removing the detergent. These occurred preferentially by the association of more
      than 10 S-protein trimmers. These S-rosettes in collaboration with either N or M
      proteins elicited TGEV-specific antibodies with titers up to 84 and 60%,
      respectively, of those induced by the whole virus. N-protein could be partially
      substituted by a 15-mer peptide that represents a T helper epitope previously
      identified in N-protein (Anton et al. (1995)). These results indicate that the
      induction of high levels of TGEV-specific antibodies requires stimulation by at
      least two viral proteins, and that optimum responses are induced by a combination
      of S-rosettes and the nucleoprotein.

PMID- 9029785
TI  - Identification and analyses of glycoprotein B of human herpesvirus 7.
AB  - The gene for the human herpes virus 7 (HHV-7) glycoprotein B (gB) has been
      identified by sequencing a molecularly cloned HHV-7 DNA fragment. A 2.5-kb open
      reading frame (ORF) encoded a protein of 822 amino acids with characteristics of
      a transmembrane glycoprotein, and showed the strongest similarity (56.5%) with
      the human herpesvirus 6 (HHV-6) gB. The genes for the transport/capsid assembly
      protein (tp/cap) and the DNA polymerase (pol) existed upstream and downstream of
      the gB gene, respectively. This arrangement was the same as that of HHV-6.
      Antisera were generated by immunizing mice with a glutathione S-transferase
      carboxy terminal gB fusion protein. Immunofluorescent tests demonstrated that the
      antisera reacted specifically with HHV-7 antigens in cytoplasm of infected cells.
      The antisera immunoprecipitated proteins with apparent molecular masses of 51, 63
      and 112 kDa from HHV-7 infected cells by pulse-chase analysis. In the presence of
      tunicamycin, the protein with a molecular mass of 112 kDa was replaced by a
      protein with a molecular mass of 88 kDa, and this size was consistent with the
      predicted size of the primary translation product of the HHV-7 gB gene. These
      results suggested that the protein with a molecular mass of 112 kDa was a
      glycoprotein synthesized by addition of N-linked oligosaccharides to a non
      glycosylated precursor of the protein with a molecular mass of 88 kDa and then
      cleaved into the proteins with molecular masses of 51 and 63 kDa in HHV-7
      infected cells.

PMID- 9029786
TI  - Serial passage of human immunodeficiency virus type 1 generates misalignment
      deletions in non-essential accessory genes.
AB  - Human immunodeficiency virus type 1 (HIV-1) derived from an infectious molecular
      clone pNL432 was extensively passaged in tissue culture by repeated rounds of
      acute infection. We previously showed the natural occurrence of a nonsense
      mutation in the vpr gene during continued passage of this virus. In this report,
      we show that two forms of large deletions (561 and 518 base pairs containing
      short direct repeats at the deletion junctions) occur after passage 50 in the
      region that spans the vif and vpr open reading frames. One model to explain the
      occurrence of these deletion regions is that such mutations result from
      misalignment of the growing point at a limited number of nucleotide positions.
      Infection of CD4+ T-cells with a recombinant HIV-1 construct containing the same
      vif to vpr deletion showed virtually no cytopathogenic phenotype. Thus,
      misalignment deletions at non-essential accessory genes of HIV-1 might be induced
      during replication, which result in the generation of virus with a low
      cytopathogenic potential.

PMID- 9029787
TI  - Mutational analysis of bacteriophage phi CTX cos site.
AB  - The DNA of phi CTX contains the gene ctx, located closely downstream of cos. This
      encodes for the pore-forming cytotoxin protein, CTX. phi CTX converts some
      Pseudomonas aeruginosa strains into CTX producers. After different periods of phi
      CTX infection, two distinct forms of phage DNA were isolated: circular DNA from
      bacterial cytosol and later linear DNA from phi CTX particles. When circular phi
      CTX DNA was transfected into the P. aeruginosa strains CF5 and E40, phi CTX was
      amplified and ctx expressed. phi CTX induced a protein fraction in CF5 cells that
      cleaved the 0.477 kb cos fragment at the cos site, indicating terminase activity.
      Deletion and point mutation variants of the cos DNA were prepared. Protein
      binding to DNA in vitro and competition experiments in vivo showed that portions
      of the cos site and its flanking sequences are differentially critical to the
      binding of phi CTX-induced proteins.

PMID- 9029788
TI  - Expression and distribution of the receptors for coxsackievirus B3 during fetal
      development of the Balb/c mouse and of their brain cells in culture.
AB  - This study was designed mainly to determine the relationships between the
      expression and distribution of the cellular receptor proteins for coxsackievirus
      B3 (CVB3) and susceptibility of mouse brain cells during fetal development of
      Balb/c mice. Immunoblot analysis of fetal extracts demonstrated that the CVB3
      receptor proteins were first expressed at day 14 of the fetal stage, and that
      maximal expression of the cellular receptor occurred at near term or newborn
      stage. Results also suggested that newborn mouse brain tissue expressed much
      larger quantities of viral receptor proteins, compared to other tissues. In vitro
      studies showed that both mouse neurons and astrocytes could be infected by two
      CVB3 strains, pantropic CVB3 Nancy strain (CVB3N) and myocardiotropic CVB3
      Woodruff strain (CVB3W). CVB3N, however, replicated and grew to high titer in
      primary astrocyte cultures and in primary neuron cultures, whereas, primary
      astrocyte cultures were relatively resistant to CVB3W. Virus binding assays
      revealed that CVB3N bound faster and in greater amounts to mouse brain cells than
      CVBW. These two virus strains, however, were found to share the same receptor
      specificity by virus competition assays. The number of virus binding sites for
      CVB3 on newborn mouse brain cells was approximately 1.8 x 10(4) per cell. The
      data suggested that preferential expression of the cellular receptors on newborn
      mouse brain cells may be related to their high susceptibilities to CVB3
      infection.

PMID- 9029790
TI  - A contribution to the systematization of bovine herpesvirus 1 based on genomic
      mapping by restriction fragment pattern analysis.
AB  - Fourteen isolates of bovine herpesvirus 1 (BHV-1) found representative of more
      than 100 isolates studied, were compared by restriction fragment pattern analyses
      and molecularly characterized. A number of evolutionary links between the
      variants originally associated with infectious bovine rhinotracheitis and the
      variants originally associated with infectious pustular vulvovaginitis were
      identified. These findings, as well as the lack of any correlation between genome
      type and clinical manifestation, confirm that there is no phylogenetic basis for
      a distinction between groups of strains associated with genital and respiratory
      disease. Two attenuated vaccine strains can be identified as deviating from field
      isolates.

PMID- 9029789
TI  - Polyomavirus large T antigen zinc finger is not required for efficient cellular
      immortalization of primary rat embryo fibroblasts.
AB  - The polyomavirus large T antigen contains a zinc finger domain required for the
      formation of hexamers involved in viral DNA replication. Since mutations within
      the zinc finger domains of transforming proteins like SV40 large T antigen and
      human papilloma virus E7 protein generally decrease their overall transforming
      activity, we have examined the ability of a mutant polyomavirus large T antigen
      that harbors a deletion in sequences within the zinc finger motif to immortalize
      primary rat embryo fibroblasts. In contrast to result obtained with SV40 large T
      antigen and the human papilloma virus E7 protein we show that deletion of the
      entire zinc finger motif enhances the immortalization efficiency of this mutant T
      antigen.

PMID- 9029791
TI  - A recently silenced, duplicate PgiC locus in Clarkia.
AB  - Previous electrophoretic analysis showed that 17 diploid species of the
      wildflower Clarkia (Onagraceae) have two cytosolic isozymes of phosphoglucose
      isomerase (PGIC; EC 5.3.1.9), whereas 15 other diploid species have a single
      PGIC. Molecular studies revealed that the two isozymes in the former species are
      encoded by duplicate genes, PgiC1 and PgiC2, whereas the single isozyme in the
      latter is always encoded by PgiC1. Phylogenetic analysis of the nucleotide
      sequences implied that PgiC2 was silenced four times independently in the genus.
      Here we describe a psi PgiC2 from C. mildrediae, a species in which only PgiC1 is
      expressed. The discovery of the psi PgiC2 is significant because it confirms a
      formal prediction of the phylogenetic analysis. The psi PgiC2 includes 5,039
      nucleotides corresponding to 18 of the 23 exons of PgiC, as well as the
      intervening introns and 3' nontranslated region. The absence of an increase of
      nucleotide substitutions in its "exons" suggests that the gene was silenced
      recently. The present study appears to be the first to establish that a specific
      duplicate gene locus regularly expressed in a group of related plant species has
      been silenced in one of them. The multiple independent silencings of PgiC2
      suggest that it remained functional but inessential in ancestral lineages. We
      discuss the possibility that PgiC2 may have been preserved in these lineages by
      selection against mutants causing defective PGIC1-PGIC2 heterodimers.

PMID- 9029792
TI  - The ability to form intrastrand tetraplexes is an evolutionarily conserved
      feature of the 3' end of L1 retrotransposons.
AB  - Mammalian genomes contain many thousands of members of a family of
      retrotransponsons known as L1 (or LINE-1) elements. These elements lack long
      terminal repeats (LTRs), and are thought to use a retroposition mechanism than
      differs from that of retroviruses and other LTR-containing retroelements. In
      order to define those regions of the L1 element that may be important for L1
      retroposition, we examined the 3' untranslated regions (UTRs) of L1 elements from
      a diverse group of mammals. We show that while the 3' UTRs of L1 elements from
      different species share little if any sequence homology, they all contain a G
      rich polypurine tract of variable length and sequence which can form one or more
      intrastrand tetraplexes. This conservation over the 100 Myr since the mammalian
      radiation suggests that either the G-rich motif itself or a conserved structure
      such as the tetraplex that can be formed by this motif is a significant
      structural feature of L1 elements and may play a role in their propagation.

PMID- 9029793
TI  - A large-subunit mitochondrial ribosomal DNA sequence translocated to the nuclear
      genome of two stone crabs (Menippe).
AB  - Two DNA sequences that appear to be homologous to large-subunit mitochondrial
      ribosomal RNA genes have been identified in the stone crabs Menippe mercenaria
      and M. adina. Amplification from whole genomic DNA by polymerase chain reaction
      (PCR) with oligonucleotide primers based on conserved portions of large-subunit
      mitochondrial rRNA genes consistently amplified two products of similar length
      (565 and 567 bp). These products differed at 3% of their nucleotide bases, and
      could be distinguished by a HindIII site. Only one of these sequences (designated
      the A sequence) was detected by PCR in purified mitochondrial DNA. The other
      (designated the B sequence) hybridized to total genomic DNA at a level consistent
      with a nuclear genome location. It is unlikely that the type B product would have
      been recognized as a nuclear copy by examination of its sequence alone. This is
      the first report of a mitochondrial gene sequence translocated into the nuclear
      genome of a crustacean.

PMID- 9029794
TI  - Mitochondrial and nuclear genes present conflicting portraits of human origins.
AB  - Human mitochondrial DNA (mtDNA) sequences reveal an abundance of polymorphic
      sites in which the frequencies of the segregating bases are very different. A
      typical polymorphism involves one base at low frequency and the other base at
      high frequency. In contrast, nuclear gene data sets tend to show an excess of
      polymorphisms in which both segregating bases are at intermediate frequencies. A
      new statistical test of this difference finds significant differences between
      mtDNA and nuclear gene data sets reported in the literature. However, differences
      in the polymorphism patterns could be caused by different sample origins for the
      different data sets. To examine the mtDNA-nuclear difference more closely, DNA
      sequences were generated from a portion of the X-linked pyruvate dehydrogenase E1
      alpha subunit (PDHA1) locus and from a portion of mitochondrial control region I
      (CRI) from each of eight individuals, four from sub-Saharan Africa. The two genes
      revealed a significant difference in the site frequency distribution of
      polymorphic sites. PDHA1 revealed an excess of intermediate-frequency
      polymorphisms, while CRI showed an excess of sites with the low-high frequency
      pattern. The discrepancy suggests that mitochondrial variation has been shaped by
      natural selection, and may not be ideal for some questions on human origins.

PMID- 9029795
TI  - Structural conservation and variation in the mitochondrial control region of
      fringilline finches (Fringilla spp.) and the greenfinch (Carduelis chloris).
AB  - We sequenced the entire control region and portions of flanking genes (tRNA(Phe),
      tRNA(Glu), and ND6) in the common chaffinch (Fringilla coelebs), blue chaffinch
      (F. teydea), brambling (F. montifringilla), and greenfinch (Carduelis chloris).
      In these finches the control region is similar in length (1,223-1,237 bp) and has
      the same flanking gene order as in other birds, and contains a putative TAS
      element and the highly conserved CSB-1 and F, D, and C boxes recognizable in most
      vertebrates. Cloverleaf-like structures associated with the TAS element at the 5'
      end and CSB-1 at the 3' end of the control region may be involved with the stop
      and start of D-loop synthesis, respectively. The pattern of nucleotide and
      substitution bias is similar to that in other vertebrates, and consequently the
      finch control region can be subdivided into a central, conserved G-rich domain
      (domain II) flanked by hypervariable 5'-C-rich (domain I) and 3'-AT-rich (domain
      III) segments. In pairwise comparisons among finch species, the central domain
      has unusually low transition/transversion ratios, which suggests that increased G
      + T content is a functional constraint, possibly for DNA primase efficiency. In
      finches the relative rates of evolution vary among domains according to a ratio
      of 4.2 (domain III) to 2.2 (domain I) to 1 (domain II), and extensively among
      sites within domains I and II. Domain I and III sequences are extremely useful in
      recovering intraspecific phylogeographic splits between populations in Africa and
      Europe, Madeira, and a basal lineage in Nefza, Tunisia. Domain II sequences are
      highly conserved, and are therefore only useful in conjunction with sequences
      from domains I and III in phylogenetic studies of closely related species.

PMID- 9029796
TI  - Transposition rate of the 412 retrotransposable element is independent of copy
      number in natural populations of Drosophila simulans.
AB  - The transposition and excision rates of the 412 retrotransposable element were
      estimated in five populations of Drosophila simulans differing in their average
      412 copy numbers, which ranged from 2 to 54. The transposition rate was found to
      equal 1 x 10(-3) to 2 x 10(-3), independently of copy number. No excision was
      detected. These values eliminate autoregulation as a force maintaining copy
      number of the 412 element in natural populations of D. simulans.

PMID- 9029798
TI  - Estimating the age of the common ancestor of a sample of DNA sequences.
AB  - We present a simple Monte Carlo method for estimating the age of the most recent
      common ancestor (MRCA) of a sample of DNA sequences. We show that Templeton's
      (1993) estimator of the age of the MRCA based on the maximum number of nucleotide
      differences between two sequences in a sample is inaccurate, and we demonstrate
      the new method by reanalyzing a sample of DNA sequences from human Y chromosomes
      and a sample of human Alu sequences.

PMID- 9029799
TI  - Evolution of mitochondrial genomes in yeast: a study of mitochondrial divergence
      in two closely related species, Saccharomyces douglasii and Saccharomyces
      cerevisiae.

PMID- 9029800
TI  - Microsatellite loci are not conserved across the Asteraceae.

PMID- 9029801
TI  - Fluoride supplement dosage. British Dental Association, the British Society of
      Paediatric Dentistry and the British Association for the Study of Community
      Dentistry.

PMID- 9029802
TI  - Treating restorative dentistry to health.

PMID- 9029803
TI  - Treating restorative dentistry to health.

PMID- 9029805
TI  - Vocational training.

PMID- 9029804
TI  - The limits of scientific dentistry or over the counter therapeutics?

PMID- 9029806
TI  - Trends in the referral and treatment of new patients at a free emergency dental
      clinic since 1989.
AB  - AIM: To investigate the changes in the pattern of new patient referral and
      treatment at a dental hospital emergency clinic since the introduction of the new
      dental contract in 1989. DESIGN: A prospective survey and review of clinical
      records. SETTING: The examination and emergency clinic at Cardiff Dental
      Hospital. SUBJECTS: 500 consecutive new patients attending the clinic in May/June
      in 1989, 1993, 1994 and 1995. MAIN OUTCOME MEASURES: Numbers of referrals; source
      of referral; geographical distribution of patients; registration with general
      dental practitioners; type of dental disease; treatment received. RESULTS: New
      patient attendances increased by 56% since 1989. Referrals from family doctors
      and dentists decreased while self-referrals increased. Self-referral by patients
      not registered with family dentists increased by 56%. Extraction of teeth was the
      commonest form of treatment in all years and increased by 72%. CONCLUSIONS:
      Numbers of patients attending for dental treatment at this setting increased
      substantially after 1989. Increasing numbers of these patients were
      inappropriately self-referred for treatment. Patients increasingly selected
      extraction of teeth as the primary treatment rather than restorative procedures.
      These changes appeared to be unrelated both to the severity of dental disease at
      presentation and to socio-economic status.

PMID- 9029807
TI  - A laboratory evaluation of two brands of disposable air turbine handpiece.
AB  - OBJECTIVE: To report on the essential performance characteristics of two brands
      of disposable air turbine handpiece and on aspects of their safety and
      convenience for clinical use. MATERIALS AND METHODS: Oralsafe and Feathertouch
      disposable handpieces were characterised using a variety of techniques in respect
      of the following: turbine rotor radius, equivalent orifice radius, stall torque
      coefficient, pressure effectiveness, power index, efficiency index, sound level
      and instrument retention force. RESULTS: Free-running speed versus pressure
      curves for many of the disposable handpieces showed marked deviations from the
      expected smooth form. Considerable variation between examples of each type was
      found in most measured values. Evidence of eccentric rotors and high bearing
      friction was not found. CONCLUSIONS: Both brands of disposable handpiece had a
      number of problems: poor performance, vibration, excessive noise, variability of
      behaviour, poor bearings. Use of these devices is difficult to recommend.
      Improvement in design seems necessary.

PMID- 9029808
TI  - Opinions of dental consultants on the standard of referral letters in dentistry.
AB  - AIM: To ascertain the views of dental consultants on the relative importance of a
      range of topics relevant to specialist referral. SUBJECTS: 200 randomly selected
      dental consultants working in the UK in 1995. MAIN OUTCOME MEASURES: Data items
      which referral letters should contain; standard of referral letters; appropriate
      reasons for referral; how referrals could be improved; should restrictions be
      placed on specialist referrals. RESULTS: 161 replies were received. Overall there
      was only slight variation between specialities with regard to data items,
      appropriateness of referral and standard of referral letter. The perceived
      standard of referral letters was adequate or better on 76% of occasions; 21% were
      deemed to be of a poor standard; 2% were described as appalling. CONCLUSIONS: A
      Section 63 course on how to refer competently could be of benefit. Consultants
      were generally not in favour of restricting referrals to them.

PMID- 9029810
TI  - The shape of things to come?
AB  - This fourth paper in the Future of Dentistry series examines the future of dental
      practice, particularly in terms of the National Health Service. David Watson
      James' vision is, he explains, intrinsically linked to past and present
      developments in dentistry and as the last 50 years has seen dental practice
      largely influenced by the creation of the NHS, he looks at its importance and
      relevance in years to come.

PMID- 9029811
TI  - Centenary year of scientific papers in the British Dental Journal.
AB  - It was no accident that Warren Harvey's paper on 'Tooth temperature with
      reference to dental pain while flying' was published during the Second World War,
      as Harvey was given the opportunity to investigate this subject after aircrew
      reported dental problems during flight. Group Captain Peter Richardson of the RAF
      Institute of Dental Health and Training reviews the paper.

PMID- 9029809
TI  - Clinical evaluation of an anterior hybrid composite resin over 8 years.
AB  - AIM: To evaluate the performance of an anterior hybrid composite resin
      restorative material (Opalux). DESIGN: Single-centre clinical trial. MATERIALS
      AND METHODS: Scores were obtained based on USPHS criteria for marginal
      adaptation, anatomic form, colour match, surface roughness and marginal
      discolouration. INTERVENTIONS: The restorative material was evaluated in suitable
      cavities in 24 patients (12 male, 12 female). Ethical permission and consent were
      obtained. MAIN OUTCOME MEASURES: Baseline data was collected on 44 restorations
      (25 Class III, 3 Class IV, 16 Class V) and reviewed independently by two of the
      three clinicians who contributed to the study who then reached a consensus score.
      Restorations were reviewed and scored in the same way at 3 months and 1, 2, 3 and
      8 years. RESULTS: The total number of alpha ratings at baseline and review (3
      months and 1, 2, 3 and 8 years) appointments for the following parameters were:
      marginal adaptation (33, 28, 29, 27, 12, 17), anatomic form (39, 30, 32, 26, 17,
      15), surface roughness (34, 26, 24, 23, 11, 4), colour match (24, 25, 26, 24, 15,
      12) and marginal discolouration (39, 31, 30, 25, 10, 9). The incidence of
      secondary caries was very low. Life table analysis suggests a 73% survival, with
      no scores below B, at 8 years. CONCLUSIONS: The majority of these restorations
      continued to perform satisfactorily. Although this particular material is no
      longer available, these results may be applicable to currently available similar
      materials.

PMID- 9029812
TI  - Gramicidin channels--a solvable membrane "protein" folding problem.
AB  - The linear gramicidins are peptide antibiotics that form cation-selective
      channels in lipid bilayers. Gramicidin channels have very well-defined functional
      characteristics, and the structure of membrane-spanning gramicidin A channels is
      known at atomic resolution. These features make the gramicidins well suited to
      study how the amino acid sequence encodes the structure and function of a
      membrane-spanning channel. We show how one can use electrophysiological
      measurements to obtain structural information about conducting channels and to
      quantify the conformational preferences of sequence-substituted gramicidin
      mutants.

PMID- 9029813
TI  - Acylation of proteins: recent advances.
AB  - The biochemistry and cell biology of covalent attachment of the fatty acids
      palmitic and myristic to proteins has been the subject of extensive
      investigations during the past fifteen years. While the site of attachment of
      fatty acids and the primary structure of proteins around the acylation site have
      been extensively documented, the exact role of the fatty acids have only been
      speculated upon. Since fatty acids would prefer to be associated with the lipid
      bilayer of membranes, it has been assumed that the role of the fatty acid is to
      provide a stable membrane anchor. This review discusses recent reports in the
      area of fatty acylation which suggests roles for the fatty acid other than that
      of a stable membrane anchor.

PMID- 9029815
TI  - Stability of D-amino acid oxidase: denaturation by guanidine hydrochloride and
      urea.
AB  - The guanidine hydrochloride-induced and urea-induced denaturations of swine D
      amino acid oxidase (EC 1.4.3.3) dimer were studied by the measurements of the
      difference absorption spectra in the near-ultra violet region and specific
      activity. Spectral measurements were made at different pH values (8.3 and 3.2)
      and temperatures (27, 37 and 47 degrees C). It has been observed that (1), enzyme
      looses all its activity in concentrated solutions of the denaturants, and (2),
      the product of urea and guanidine hydrochloride denaturation is only partially
      unfolded as judged by the measurements of the intrinsic viscosity and exposures
      of the tyrosyl, tryptophyl and sulphhydryl residues.

PMID- 9029816
TI  - Purification and kinetic characterization of chicken liver inorganic
      pyrophosphatase.
AB  - Soluble inorganic pyrophosphatase (EC 3.6.1.1) was isolated from chicken liver,
      RIR breed, to apparent homogeneity. The enzyme showed a molecular mass of 100 kDa
      as estimated by gel filtration and a subunit mass of 49 kDa on SDS-PAGE. The
      enzyme was very specific for pyrophosphate (PPi) and magnesium, and there was no
      measurable activity on replacing Mg2+ with Zn2+. At optimal conditions of assay,
      50% of the enzyme activity was inhibited at 42 microM Ca2+, 70 microM fluoride
      and 0.91 mM Cd2+. There was a 50% inactivation of enzyme activity at 0.1 M
      guanidine hydrochloride (GuHCl). Kinetic analysis of GuHCl inactivation revealed
      2 essential binding sites for this ligand. The enzyme showed allosteric behaviour
      with the substrate PPi and Mg2+. The apparent Hill coefficient of 1.47 and 1.48
      for PPi and Mg2+, respectively indicate positive cooperatively. Hill plots also
      gave [S]0.5 of 0.177 mM and 2.5 microM for Mg2+ and PPi, respectively.

PMID- 9029814
TI  - Lag kinetics of tyrosinase: its physiological implications.
AB  - The various theories put forward to explain the characteristic lag kinetics of
      oxidation of L-tyrosine by tyrosinase a rate regulatory step in the biosynthesis
      of melanin are reviewed Examination of the evidence in the literature and from
      experiments in the author's laboratory indicate that one of the hypotheses, that
      is, competition of tyrosine and dopa for met-tyrosinase and the formation of a
      dead-end complex of met-enzyme with tyrosine as explanation for lag kinetics is
      not consistent with available information. The alternative hypothesis that
      tyrosinase is an allosteric enzyme with tyrosine having negative effector site on
      the enzyme and dopa competing for it as an explanation for lag kinetics of
      tyrosinase is not yet disproved. Irrespective of the actual explanation for the
      lag kinetics of tyrosinase, it is suggested that the highly conserved lag
      kinetics may serve a physiological function. It is suggested that this function
      is to keep the enzyme essentially inactive during its transport to the specific
      organelle, namely the melanosome, in which an acidic environment exists. Only at
      acidic pH is the enzyme able to catalyze the biosynthesis of melanin.

PMID- 9029817
TI  - Purification and preliminary characterization of L-asparaginase from Erwinia
      aroideae NRRL B-138.
AB  - L-Asparaginase (L-asparagine amidohydrolase EC 3.5.1.1) from Erwinia aroideae
      NRRL B-138 has been purified to apparent homogeneity by ammonium sulphate
      precipitation, chromatography on sulfopropyl-sephadex C-50 and sephadex G-200
      with 22% recovery and 567-fold purification. The enzyme obtained from sulfopropyl
      sephadex C-50 was unstable and lost activity within a few hours. Addition of
      glycerol helped in restoring the activity of the enzyme. The enzyme has an
      apparent molecular mass of approximately 155 kDa and has four subunits of
      identical molecular mass of approximately 38 kDa. The K(m) for L-asparagine is
      2.8 x 10(-3) M. Enzyme shows optimal activity at 45 degrees C and pH 8.2. Energy
      of activation as determined from Arrhenius plot was 9.1 kcal/mol. Substrate L
      asparagine and analogue L-glutamine, D-asparagine and 6 diazo-5-oxo-L-norleucine
      provide full protection to the enzyme against thermal denaturation.

PMID- 9029818
TI  - Influence of Ca2+ on kinetics and thermodynamics of the NADPH-dependent
      microsomal lipid peroxidation.
AB  - The effect of Ca2+ on kinetics and thermodynamics of lipid peroxidation in
      microsomes prepared from liver of male Swiss albino mice (7-8 weeks old) was
      studied. Ca2+ was found to increase the Vmax in temperature dependent manner.
      Michaelis-Menten constant (Km) also increased with temperature. However, the
      linearity and extent of change in Km remained unaffected in presence of Ca2+, and
      was suggestive of non-competitive and mixed type of activation. The activation
      constant (Ka) obtained by the replotting of slopes of the Lineweaver-Burk plots
      against the reciprocal of Ca2+ concentration showed linear variation with
      temperature. The linear pattern of Arrhenius plots indicated non-involvement of
      parallel reactions of other intermediate species in the lipid peroxidation.
      Thermodynamic parameters delta H degree, delta S degree and delta G degree,
      associated with lipid peroxidation process were studied. The positive value of
      delta H degree is suggestive of the endothermic nature of the process. It appears
      that the NADPH induced lipid peroxidation is an entropy driven process.

PMID- 9029819
TI  - Probing tenability of biochemical vis-a-vis physicochemical interpretations of
      modulation of radiation damage by caffeine and cysteine in barley.
AB  - Cysteine (an aminothiol) is known to protect against radiation damage, and is
      understood to do so by generating hydrogen peroxide which subsequently inhibits
      RNA synthesis. Our results showed inability of catalase to remove or reduce the
      magnitude of radioprotection by caffeine and/or cysteine at optimal/suboptimal
      temperatures in barley. This observation was adequately corroborated by data on
      frequency of chromosomal aberration, peroxidase activity and total protein
      content. On the contrary, catalase tended to enhance the radioprotective
      effectiveness of cysteine. Macromolecular synthetic patterns in caffeine and/or
      cysteine treated embryos were too inconsistent to permit a logical conclusion
      with regard to their positive involvement in the biochemical pathway of chemical
      modification of radiation damage. On the other hand, mutually annihilatory
      reaction hypothesis based on physico-chemical principles provides a satisfactory
      explanation for the observed effects.

PMID- 9029820
TI  - Molecular mechanics calculations of opioid ligands of the 4-arylpiperidine class.
AB  - Molecular mechanics calculations have been carried out on N-methyl-4-phenyl-4
      piperidinols substituted at 2,3-, 2,5- and 2,6-positions with methyl groups.
      Besides the alcohols, their esters and methiodides were also studied. The
      molecular mechanics conformations have been compared with conformations
      determined experimentally by NMR or X-ray diffraction.

PMID- 9029821
TI  - The possible role of surface charge in membrane organization in an acidophile.
AB  - Thiobacillus ferrooxidans, an obligate acidophile, possesses an electron
      transport chain that uses oxidation of ferrous iron to generate proton motive
      force. The cells possess an efficient machinery for inter-conversion of the two
      components of the free energy, namely pH gradient and membrane potential.
      Incidentally, unlike most of the naturally occurring membranes, surface in T.
      ferrooxidans appears to be positively charged at or near its physiological pH.
      Independent estimate of such charge was obtained from binding studies with
      anionic optical and fluorescent probes. When the external pH is lowered below a
      critical value the inter-conversion of the two components of the proton motive
      force was no longer operative. A surface charge mediated phase separation of
      membrane is suggested as one of the possible mechanisms for the failure of such
      inter-conversion process.

PMID- 9029822
TI  - Near ultraviolet radiation induced changes in goat lens.
AB  - The possibility that the ultraviolet radiation from sunlight and other ambient
      sources as a major causative factor for the onset of cataract processes and
      photolytic changes of the eye lens constituents was studied. Normal goat lenses
      exposed in vitro to near UV radiation in the region of 315-400 nm (UV-A) revealed
      distinct morphological changes in the ultrastructure, increase in the inorganic
      elements; C, H, N, and a sharp shift in the intrinsic fluorescence spectra. UV
      exposure resulted in an alteration in the lambda max of the excitation spectra, a
      red shift in the emission absorption maxima and also an increase in the absolute
      fluorescence intensity. Scanning electron microscopic study showed a significant
      increase in the interfibrillar distances of the lens structural proteins. It is
      argued that the UV light induced covalent modifications of the lens proteins and
      their aggregations might have occurred due to the generation of photolytic
      products which then lead to oxidative damages.

PMID- 9029823
TI  - Effect of enterotoxin on glutathione status in the intestinal mucosa.
AB  - The effect of luminal exposure of enterotoxins on the intestinal mucosal
      glutathione (GSH) was studied in rat. Cholera toxin induced fluid secretion and
      decreased mucosal GSH by 35% without altering oxidized glutathione (GSSG) level.
      Toxin induced fluid secretion was tested after mucosal GSH depletion by compounds
      such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) and thiol
      supplementation with N-Acetyl cysteine (NAC). Fluid secretion was not altered by
      prior thiol depletion or supplementation. Exposure of intestinal lumen to
      bacterial endotoxin resulted in 25% decrease in mucosal GSH with two fold
      increase in GSSG. Luminal exposure of Shiga toxin did not alter the mucosal
      thiol. The level of other low molecular weight thiols, cysteine and cystine was
      not altered by luminal exposure of any of these toxins. These results show that
      although cholera toxin decreased the mucosal GSH level, prior modulation of thiol
      status of the mucosa may not have any effect on toxin-induced fluid secretion.

PMID- 9029824
TI  - Involvement of a protease in tert-butylhydroperoxide-mediated activation of Ca2+
      ATPase in microsomes of pulmonary smooth muscle.
AB  - Microsomes isolated from bovine pulmonary artery smooth muscle tissue treated
      with the oxidant t-buOOH stimulated Ca2+ ATPase activity dose-dependently as also
      protease activity when tested with a synthetic substrate N-benzoyl-DL-arginine p
      nitroanilide. At 300 microM, t-buOOH optimally stimulated these activities.
      Treatment of the microsomes with t-buOOH stimulated ATP dependent Ca2+ uptake
      while Na+ dependent Ca2+ uptake was inhibited by t-buOOH. Pretreatment of the
      microsomes with vitamin E (1 mM) and aprotinin (1 mg/ml) prevented t-buOOH caused
      stimulation of protease activity and Ca2+ ATPase activity, and also stimulation
      of ATP dependent Ca2+ uptake while t-buOOH caused inhibition of Na+ dependent
      Ca2+ uptake was reversed by vitamin E and aprotinin. Treatment of the microsomes
      with trypsin (1 microgram/ml) stimulated Ca2+ ATPase and ATP dependent Ca2+
      uptake while Na+ dependent Ca2+ uptake was inhibited. Pretreatment of the
      microsomes with aprotinin prevented trypsin caused stimulation of Ca2+ ATPase and
      ATP dependent Ca2+ uptake, while trypsin caused inhibition of Na+ dependent Ca2+
      uptake was reversed by aprotinin.

PMID- 9029825
TI  - Changes in the cellular composition of Candida albicans resistant to miconazole.
AB  - Biochemical changes that accompany acquisition of miconazole resistance in a
      single step mutant of C. albicans 3153 were analyzed. Experiments show that
      resistance to this drug was associated with decrease in total lipids,
      phospholipids and sterol content. Fluorescence polarization studies with 1,6
      diphenyl-1,3,5-hexatriene (DPH) showed decrease in polarization value (p) in
      resistant cells, thus indicating changes in membrane fluidity. Uptake of [3H]
      proline by intact cells revealed decrease in K(m) and Vmax of high affinity
      system (S1) of proline transport in cells resistant to miconazole. Results of
      this study suggest that membrane sensitivity of miconazole is determined by
      overall membrane organisation rather than by affinity of antifungal drug(s) for a
      single membrane component.

PMID- 9029826
TI  - Thiocarbamate linkage as internucleoside bond.

PMID- 9029827
TI  - Glutamate dehydrogenase induction in the brain of streptozotocin diabetic rats.

PMID- 9029829
TI  - Rapid identification of Campylobacter jejuni strains by polymerase chain reaction
      & their restriction fragment length polymorphism analysis.
AB  - A polymerase chain reaction (PCR) technique was developed for specific
      identification of C. jejuni. A primer pair of a conserved region of flagellin A
      (fla A) gene identified all 15 strains of C. jejuni isolated from human faeces.
      None of the control strains like Helicobacter pylori, Vibrio cholerae Escherichia
      coli and Salmonella typhimurium except C. coli exhibited any amplified product by
      PCR. A predicted 450 bp could also be amplified from 4 chicken caecal contents
      positive for C. jejuni-C coli by culture. The caecal contents remained positive
      for C. jejuni-C. coli by PCR after preservation at 4 degrees C for one week when
      no viable organism could be detected. Restriction fragment length polymorphism
      analysis (RFLP) of fla A amplified product by using Bgl II enzyme classified 15
      strains into 5 types. Three C. jejuni strains isolated from the same patient over
      a period of 3 wk showed the same RFLP pattern. The present study indicates that
      PCR is specific for C. jejuni-C. coli and it has the potential for rapid
      diagnosis of infection. RFLP can be a good epidemiological marker for C. jejuni
      infection.

PMID- 9029828
TI  - Blood stem cell transplantation: current concepts.
AB  - Mobilized peripheral blood haematopoietic progenitor cells are increasingly being
      used as against bone marrow (BM) transplants, following high dose chemotherapy
      and/or radiotherapy for the management of chemosensitive malignancies. Rapid
      haematopoietic reconstitution as evidenced by reduced duration of neutropaenia,
      fewer donor platelet infusions, shorter hospital stay and reduced cost of
      treatment are the advantages of this procedure. Reduced tumour cell contamination
      of mobilized blood compared to bone marrow however, has not been substantiated.
      Mobilization of lymphokine activated killer cells (LAK), use of blood stem cells
      (BSC) for allogeneic transplants and ex vivo expansion of the mobilized cells are
      emerging as the future areas for research. Addition of interleukin-3 (IL-3), stem
      cell factor (c-kit ligand) and PIXY-321 appear to open-up new vistas by enforcing
      trilineage and multilineage haematopoietic reconstitution.

PMID- 9029830
TI  - Upper urinary tract stones & Ureaplasma urealyticum.
AB  - Extensive culture of stones and of pre-operative and renal pelvic urine for
      isolation of bacteria and Ureaplasma urealyticum were performed in 70 patients of
      nephrolithiasis. Stones were subjected to biochemical analysis and scanning
      electron microscopy. Micro-organisms were isolated from 33 (47%) of 70 renal
      stones. Of the 38 species of micro-organisms isolated, 14 were urea-splitting (U.
      urealyticum 2; Klebsiella pneumoniae 8; Morganella morganii 1; Acinetobacter spp
      3) and 24 were nonurea splitting. U. urealyticum was cultured from the renal
      stones of two patients. Pelvic urine, unlike voided urine did reflect the
      bacteriology of the stone. Biochemically, 55 stones (79%) were calcium oxalate
      phosphate stones, 10 (14%) were calcium oxalate stones and 5 (7%) were uric acid
      stones. None of the stones were found to be of struvite composition. These data
      suggest that infection stones are uncommon in this part of the country. Further,
      infection of renal stones with fastidious organisms like U. urealyticum and multi
      drug resistant bacteria necessitate their removal to ensure complete cure.

PMID- 9029831
TI  - The changing profile of Plasmodium falciparum malaria.
AB  - Resurgence of malaria has been noted in the Rohtak district (Haryana, India)
      after the recent floods. The profile of 66 patients of P. falciparum infection
      who were admitted to our hospital over one month in October 1995 is reported.
      While only a minority of cases (< 15%) presented with an uncomplicated course,
      all others developed one or more complication(s), some of them very rare. The
      usual manifestations viz, cerebral malaria, black water fever and algid malaria
      seen in the past were observed in less than half the patients. The remaining
      presented with unusual complications like haemolytic anaemia (46.2%), severe
      anaemia (37.9%), thrombocytopaenia (18.2%), pancytopaenia (6%), adult respiratory
      distress syndrome (4.5%) often not seen in sporadic cases of falciparum malaria
      which occurred in the past in this district. Similarly all deaths (15.1%) were
      noted in patients with rarer manifestations and only one patient died of cerebral
      malaria. This study confirms the occurrence of severe and complicated falciparum
      malaria in this part of the country.

PMID- 9029832
TI  - Late onset adrenal hyperplasia due to 3 beta-hydroxy-delta 5-steroid
      dehydrogenase deficiency in north Indian hirsute women.
AB  - The presence of late onset 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD) type
      of congenital adrenal hyperplasia was studied in 58 north Indian hirsute women.
      The age range of these patients was 15 to 42 yr. Fifty two per cent of these
      patients had body mass index > 25. Basal serum testosterone, luteinizing hormone,
      follicle stimulating hormone, dehydroepiandrosterone sulphate (DHEAS), and 17
      hydroxy progesterone (17 OHP) were estimated. All the patients underwent
      adrenocorticotropin (ACTH) stimulation test after an overnight dexamethasone
      suppression for the estimation of DHEAS, 17 OHP, and 17 hydroxy pregnenolone
      (delta 5-17p). Five (8.6%) hirsute women showed an exaggerated 17 OHP response to
      ACTH indicating 21-hydroxylase deficiency. Eight (13.8%) hirsute women had
      elevated basal DHEAS and ACTH-stimulated DHEAS as well as delta 5-17P responses
      indicative of 3 beta-HSD deficiency. In one patient hirsutism was the presenting
      manifestation of tumoural hyperandrogenism. Our findings indicate the presence of
      both 21-hydroxylase and 3 beta-HSD deficiency in north Indian hirsute women,
      with, 3 beta-HSD deficiency being the major cause of hirsutism in this
      population.

PMID- 9029834
TI  - Elevated levels of anti-proteus antibodies in patients with active rheumatoid
      arthritis.
AB  - We carried out this study to determine if our patient population with rheumatoid
      arthritis (RA) has elevated levels of antibodies to gut bacteria. Seventy
      patients with RA were categorised as being either active or inactive on clinical
      grounds. Antibodies to the H and O antigens of Proteus mirabilis and Salmonella
      typhi were determined by tube agglutination method in these patients, 18 patients
      with osteoarthritis and 82 healthy controls. There was no significant difference
      in the anti-proteus antibody titres between both the control groups and patients
      with inactive disease. However, antibody levels among patients with active
      disease were significantly higher than controls (P < 0.001). There was no
      significant difference in anti-salmonella antibody titres among the various
      disease and control groups. Elevated antibody levels could suggest a role for
      Proteus as an etiological agent in RA.

PMID- 9029833
TI  - Genotype-phenotype correlation in Duchenne/Becker muscular dystrophy patients
      seen at Lucknow.
AB  - The molecular basis of two allelic forms of muscular dystrophy, Duchenne (DMD)
      and Becker (BMD), has been explained by frame shift hypothesis. In order to test
      this hypothesis, deletional mutations in 59 patients confirmed to have DMD and 11
      BMD patients were analysed using multiplex polymerase chain reaction and Southern
      hybridization with dystrophin cDNA probes. Translational reading frame of the
      dystrophin gene was derived from 'Border type' analysis of exons flanking the
      intragenic deletions. The correlation between genotype (reading frame) and
      phenotype (clinical severity) showed higher number of DMD patients (approximately
      20%) deviating from the frame shift hypothesis. The patients who deviated had
      deletions at the central hot spot region of the dystrophin gene. The presence of
      these deviations in a large number of DMD patients highlights the difficulties in
      predicting the clinical progression of the disease based only on DNA profile.

PMID- 9029835
TI  - Make the Internet work for your practice.

PMID- 9029836
TI  - New laws affecting physicians.

PMID- 9029837
TI  - Combatting fraud and abuse. Anti-kickback statute.

PMID- 9029838
TI  - Current therapy of Parkinson's disease.

PMID- 9029839
TI  - Drug-seeking patients.

PMID- 9029840
TI  - Quarterly report of the National Legal Center for the Medically Dependent &
      Disabled, Inc.

PMID- 9029841
TI  - The dilemma of "medical futility"--a "wisdom model" for decisionmaking.

PMID- 9029842
TI  - In re Martin.

PMID- 9029843
TI  - Brief of the Attorney General in Washington v. Glucksberg in the United States
      Supreme Court. No. 96-110.

PMID- 9029844
TI  - Brief of the Attorney General in Vacco v. Quill in the United States Supreme
      Court. No. 95-1858.

PMID- 9029845
TI  - Insurance crusade.

PMID- 9029846
TI  - Cellular hemangioma of the posterior mediastinum: unusual presentation of a rare
      vascular neoplasm.
AB  - Cellular hemangiomas arising in the posterior mediastinum (or paravertebral
      sulcus) are rare tumors even in childhood. We report one such tumor which arose
      within a sympathetic ganglion in an infant with associated congenital heart
      disease (ventricular septal defect) and severe congestive heart failure. The
      tumor was discovered incidentally at cardiac catheterization when tumor blush was
      observed in the apex of the left chest. This benign mass was completely resected
      prior to repair of the cardiac defect. We speculate that it may have contributed
      to the congestive heart failure.

PMID- 9029847
TI  - Alcohol consumption among Oklahoma women: before and during pregnancy. The PRAMS
      Working Group. Pregnancy Risk Assessment Monitoring System.
AB  - The Pregnancy Risk Assessment Monitoring System (PRAMS) utilizes a population
      based survey of Oklahoma women with a recent live birth to examine the rates of
      alcohol consumption before and during pregnancy. Nearly one-half of Oklahoma
      women report using alcohol during the three months before pregnancy and one in
      thirteen women consume alcohol during the three months prior to delivery.
      Moderate to heavy alcohol use before pregnancy was associated with additional
      perinatal risk factors including unintended pregnancy, inadequate prenatal care,
      smoking, and physical abuse. Health providers play an important role in the
      prevention of alcohol related birth impairments such as fetal alcohol syndrome
      through early detection of problem drinking, patient education and appropriate
      referrals. However, one in four Oklahoma mothers report their health care
      provider did not talk to them about the harmful effects alcohol can have on their
      baby.

PMID- 9029848
TI  - Managed health care: a concept not understood by rural Oklahomans.
AB  - OBJECTIVE: The purpose of the study was to find out what people in rural Oklahoma
      know and understand about managed care. METHODS: A fourteen-statement survey
      instrument was developed. A panel of managed care professionals were asked to
      participate to provide a "standard" to compare the responses of the general
      public. The survey was administered to the general public in five rural
      communities and to recipients of the Oklahoma AHEC Newsletter. RESULTS: Overall,
      the panel tended to agree and created an industry profile useful in comparison to
      the responses of the general public: (1) 55-65% of the respondents answered I
      Don't Know or Neither Agree nor Disagree to statements using the term "managed
      care" and only 15-20% of the public respondents answered I Don't Know to
      statements not including the term, "managed care." (2) 25-30% of the general
      public answered in accordance with the managed care panel. (3) Over 50% of the
      public respondents Agreed that changes are necessary in the health sector.
      CONCLUSIONS: The results of this survey suggest that rural Oklahomans are
      uninformed about the concept of managed care and need to become better informed.

PMID- 9029849
TI  - Consumer-focused preadmission testing: a paradigm shift.
AB  - The current trend in the health care environment is to redesign the delivery of
      services to make them customer friendly as opposed to hospital convenient. The
      paradigm shift meets and exceeds customers, expectations by bringing the points
      of service to the patient. Preadmission testing is accomplished by specially
      educated, registered professional nurses, who complete the nursing assessment,
      laboratory work, electrocardiograms, social and rehabilitative services
      referrals, and patient teaching in a primary care framework. This redesign
      results in a cost savings for the institution, increased patient and physician
      satisfaction, and decreased idle time for patients and staff.

PMID- 9029850
TI  - Medication self-administration: an outcome-oriented, consumer-driven program.
AB  - The ability to understand medication and consistently follow a prescribed medical
      regimen varies among the general population. The Department of Nursing at Mohawk
      Valley Psychiatric Center developed a medication self-administration program to
      help consumers gain knowledge and/or improve their ability to participate in
      medication and symptoms management. Results have demonstrated that consumers can
      learn at least one more piece of information about their illness and/or
      medication despite their level of cognitive functioning, can learn to self
      administer medications with minimal supervision before leaving the hospital, and
      can make an easier transition into the community setting.

PMID- 9029851
TI  - Implementing the Agency for Health Care Policy and Research pain management
      pediatric guideline in a multicultural practice setting.
AB  - This article describes the implementation, monitoring, and evaluation of a
      clinical practice guideline for managing pediatric patient pain. The standard of
      care used was the Agency for Health Care Policy and Research acute pain
      management guideline. It was used to assess current levels of care and to make
      recommendations for improvements. Information was gathered from a sample of 240
      pediatric patients aged 1 week to 14 years. Recommendations for improving care
      are given. The guideline was found to be clinically useful as a general standard
      of care, but more work needs to be done to individualize care for specific
      populations, age groups, and cultures.

PMID- 9029852
TI  - Nurse call systems: impact on nursing performance.
AB  - Outcries for health care reform and more cost-effective patient care have
      motivated many organizations to examine routine unit activities. The article
      reports a study that used a descriptive design to examine nursing utilization of
      and satisfaction with nurse call systems in two large metropolitan hospitals.
      Findings revealed that nurse call system features such as the ability of unit
      secretaries to receive and screen patient calls reduced unnecessary nurse
      interruptions, saved actual nursing time, and enabled some nurses to begin
      preparing to meet patients, needs before entering their rooms. Problems with the
      nurse call system identified from the data were the sound quality of the
      transmission, inability to locate the nurse, inability to prioritize and confirm
      calls, and inability to speak directly to patients and staff.

PMID- 9029854
TI  - Reducing high-risk interventions for managing aggression in psychiatric settings.
AB  - Seclusion and restraints have traditionally been major interventions for
      controlling patient aggression. The implementation of less restrictive measures
      may or may not be an option in managing individual cases of psychiatric
      emergencies. Improvement in patients, knowledge of alternatives and the need to
      reduce the use of restraints have led to the development of new tools to enhance
      prevention of high-risk interventions. At one institution, an anger management
      assessment tool and "Triangle of Choices" have assisted patients in identifying
      and managing feelings of frustration and anger. Since their inception 1 year ago,
      the implementation of documented alternatives to restraints has increased, and
      use of most restrictive measures has decreased.

PMID- 9029853
TI  - A framework for integrated quality improvement.
AB  - The importance of maintaining and improving quality is well understood in most
      health care organizations. This work becomes more challenging as internal and
      external conditions rapidly change. A quality improvement framework was developed
      to help clinicians and administrators organize intergrated, multifaceted quality
      programs that have the flexibility necessary for success in today's fast-paced
      health care environment.

PMID- 9029855
TI  - Improving patient follow-up through implementation of an ambulatory care quality
      improvement program.
AB  - Nurse practitioners in ambulatory care settings must begin using quality
      improvement strategies to enhance patient outcomes and to improve patient follow
      up. The article highlights the development and beginning stages of implementation
      of one such quality improvement program and discusses the actions that were taken
      to increase timeliness of key patient processes. An example of a quality
      improvement educational program, outlines of the plan, and scope of services are
      also provided.

PMID- 9029856
TI  - Biological indices predictive of survival in 519 Italian terminally ill cancer
      patients. Italian Multicenter Study Group on Palliative Care.
AB  - The knowledge of prognostic factors capable of subdividing cancer patients into
      groups having homogenous survival times is useful even in very advanced stages of
      illness. This prospective multicenter study assessed these prognostic factors in
      530 terminal patients with solid tumors who were undergoing only palliative care.
      Thirteen hematological and urinary parameters were assessed on admission and
      every 28 days thereafter. In 519 assessable patients with a median survival of 32
      days, six biological parameters demonstrated a statistically significant
      predictive prognosis. A poor prognosis was predicted by high total white blood
      count (WBC) (P < 0.0001), high neutrophil percentage (P < 0.0001), low lymphocyte
      percentage (P < 0.0001), low serum albumin level (P = 0.0015), low
      pseudocholinesterase level (P < 0.0001), and high proteinuria (P = 0.0064).
      Multiple regression analysis showed that only WBC, lymphocyte percentage and
      pseudocholinesterase level were independent predictors of survival. The
      individualization of biological parameters having an independent prognostic
      capacity is a useful step in the attempt to identify subsets of patients with a
      homogeneous prognosis. The biological factors needed are easily detected by means
      of a simple blood test and do not require invasive operations on patients who are
      already debilitated.

PMID- 9029857
TI  - The Edmonton Functional Assessment Tool: preliminary development and evaluation
      for use in palliative care.
AB  - The purpose of this article is to report the development and psychometric testing
      of the Edmonton Functional Assessment Tool (EFAT). The EFAT was developed as a
      functional outcome measure for use with a palliative care population. The
      assessment identified ten functional activities important to patients even in the
      terminal stage of their illness. In addition, a global performance status rating
      (PS) asked for an overall judgment of functional status after the ten EFAT
      functions were evaluated. Tests for interrater reliability and concurrent
      validity were conducted on a sample of 25 inpatients on the Palliative Care Unit
      (PCU) at the Edmonton General Hospital (EGH) who were evaluated independently by
      two raters. Interrater reliability of the EFAT expressed as an intraclass
      correlation (ICC) was established at 0.88. The interrater reliability of these
      two raters was 0.71 for the Karnofsky Performance Status (KPS) and 0.81 for the
      performance status measure of the Eastern Cooperative Oncology Group (ECOG).
      Concurrent validity of the EFAT was demonstrated by correlating the total EFAT
      score with the KPS (r = -0.79, P = 0.0001) and the ECOG (r = 0.85, P = 0.0001).
      The total EFAT score was also strongly correlated with the global PS rating scale
      (r = 0.90, P = 0.0001). Construct validity of the EFAT was tested with a sample
      of 101 patients admitted to the unit, which was later divided into the unit group
      (N = 88) and the home group (N = 13). Our findings provided initial evidence that
      the EFAT distinguished between the functional status of these two groups. The
      results of this preliminary study suggest that the EFAT requires further research
      and development, but shows potential to evolve as a useful clinical tool in
      palliative care.

PMID- 9029858
TI  - Fibrinolytic inhibitors for cancer-associated bleeding problems.
AB  - This pilot study of 16 patients explored the use of two fibrinolytic inhibitors,
      tranexamic acid and aminocaproic acid, for the suppression of tumor-associated
      hemorrhage. The effects of such bleeding include anemia requiring transfusion,
      practical difficulties with dressings, and psychological morbidity from constant
      reminder of poor physical health. Cessation of bleeding occurred in 14 of the 16
      patients treated. The average time until significant improvement in bleeding was
      just 2 days and the average time for complete cessation was 4 days. We conclude
      that fibrinolytic inhibitors are potentially useful agents in palliative care.

PMID- 9029859
TI  - Spinal epidural metastasis: implications for spinal analgesia to treat
      "refractory" cancer pain.
AB  - Two hundred one consecutive patients with cancer pain who received intrathecal
      pain treatment between 1985 and 1993 were included in this retrospective study
      undertaken to test the hypothesis that epidural metastasis is a common cause of
      "refractory" cancer pain and that its presence may affect the efficacy and the
      complication rates of intraspinal pain treatment. Fifty-seven (approximately 28%)
      patients were investigated by metrizamide myelography, computerized tomography
      (CT), magnetic resonance imaging (MRI), laminectomy, or neurohistopathology.
      Epidural metastases were found in 40 (70%) and spinal stenosis in 33
      (approximately 58%); 7 patients with total and 26 with partial occlusion of the
      spinal canal. Presence of epidural metastasis affected catheter insertion
      complications, daily dosages, and complications of the intrathecal pain treatment
      only when it was associated with spinal canal stenosis (partial or total). During
      the period of the intrathecal treatment, the patients with confirmed epidural
      metastasis and total spinal canal stenosis needed significantly (P < 0.05) higher
      daily doses of opioid (means = 77 +/- 103 versus 22 +/- 29 mg) and intrathecal
      bupivacaine (means = 65 +/- 44 versus 33 +/- 20 mg) and had significantly (P <
      0.05) higher rates (14% versus 0%) of radicular pain at injection and poor
      distribution of analgesia than those without epidural metastasis and spinal canal
      stenosis. In contrast, the rate of occurrence of post-dural puncture headache was
      significantly (P < 0.05) lower in patients with partial (4%) and total (14%)
      spinal stenosis than in those without (29%). Unexpected paraplegia occurred in
      four patients and was due to accidental injury during attempted dural puncture (N
      = 1) and collapse (due to cerebrospinal fluid leakage leading to "medullary
      coning" of an unknown epidural metastasis (N = 3).

PMID- 9029860
TI  - Subcutaneous cannulae for morphine boluses in children: assessment of a
      technique.
AB  - Indwelling subcutaneous cannula for the administration of intermittent morphine
      boluses postoperatively have been used in several centers as an alternative to
      intramuscular (IM) injections. We introduced this technique to our hospital,
      assessed it for complications in 220 children, and conducted a survey to see if
      nursing staff preferred it to IM injections. The injections through the
      subcutaneous cannulae caused minimal distress to the children. There were no
      major complications, 95% of the nursing staff preferred this technique, and 74%
      would give morphine more readily to a child with a subcutaneous cannula in situ.

PMID- 9029861
TI  - Acetaminophen in the management of background pain in children post-burn.
AB  - This retrospective review evaluated the pain management of 395 acutely burned
      pediatric patients who were treated by a pain management protocol emphasizing
      acetaminophen as the initial medication to control background pain. Pain was
      assessed by using standardized instruments based on observations by patients,
      nurses, and parents. Morphine was added when scheduled acetaminophen (10-15
      mg/kg/4 hr) did not control background pain. Fifty percent of the children
      received only acetaminophen to control background pain. Younger children and
      children with the smallest burns, regardless of age, were likely to be managed
      with acetaminophen alone. Most peak serum concentrations of acetaminophen were
      less than 10 micrograms/mL. When needed, children also received medication for
      painful procedures, anxiety, and posttraumatic stress symptoms. These additional
      medications were not more frequently given to children receiving only
      acetaminophen for background pain. These data suggest that acetaminophen is a
      safe, useful medication for the control of post-burn background pain in some
      children.

PMID- 9029862
TI  - Salmonella anatum infection in infants linked to dried milk.

PMID- 9029863
TI  - Transmission of HIV from an infected surgeon to a patient in France.

PMID- 9029864
TI  - Surveillance of HIV and AIDS in 1996.

PMID- 9029865
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 9029866
TI  - Legionnaires' disease in Corby, Northamptonshire.

PMID- 9029867
TI  - Scombrotoxic fish poisoning and imported tuna steaks.

PMID- 9029868
TI  - News media are first to catch influenza.

PMID- 9029869
TI  - Innovations for the new year.

PMID- 9029870
TI  - Management of clusters of meningococcal disease. PHIS Meningococcus Working Group
      and Public Health Medicine Environmental Group.
AB  - Guidance on the management of clustered cases of meningococcal disease has been
      revised following a review of the clusters that occurred in England and Wales
      between 1 April 1995 and 31 March 1996. Public health action is indicated for
      confirmed and probable cases but not in response to possible cases. The
      importance of microbiological confirmation is re-emphasised. Intervention is
      recommended for defined target groups when two or more confirmed or probable
      cases occur in a preschool group or school within a four week period. We present
      a framework to assist in the management of clusters of invasive serogroup C
      infections in larger and less defined communities.

PMID- 9029871
TI  - A college outbreak of group C meningococcal infection: how widely should
      investigation and prophylaxis extend?
AB  - Neisseria meningitidis group C type 2b, P1.2, P1.5 caused an outbreak of four
      cases, two of whom were members of an agricultural college in Devon, and two
      outside contacts of students who were documented carriers of the outbreak strain.
      The identification of the outbreak was made more difficult by the fact that none
      of the three cases first linked with the college was culture positive and indeed
      only one of these was actually a member of the college. Carriage of the outbreak
      strain was significantly associated with residence in college and enrollment on
      one particular course. The question was raised of whether in outbreaks of this
      type control measures should be extended beyond the confines of the affected
      institution.

PMID- 9029872
TI  - Meningococcal disease in the Republic of Ireland: 1995.
AB  - Two hundred and nine culture confirmed cases of meningococcal disease were
      reported in the Republic of Ireland in 1995, using a new laboratory based
      surveillance system. The reported rate of 5.9/100000 population is one of the
      highest in western Europe, but the rate differed widely between regions. Fifty
      three per cent of cases were female. Half of the cases occurred in four months
      (January, February, March, and December). Nineteen cases (9%) died. The highest
      age specific incidence was in infancy (under 1 year). Infections with serogroup B
      accounted for 105 cases (54%) and serogroup C 87 cases (45%). We estimate that up
      to 30% of cases of meningococcal disease may be preventable when conjugate
      meningococcal group C vaccines become available, but cost benefit analyses will
      be required to determine how they should be employed.

PMID- 9029873
TI  - Communicable diseases and the Australian Paediatric Surveillance Unit.

PMID- 9029874
TI  - Research lacking in osteopathic medical profession.

PMID- 9029875
TI  - Transurethral microwave hyperthermia: new hope for treating chronic nonbacterial
      prostatitis?

PMID- 9029876
TI  - Transurethral microwave hyperthermia in the treatment of chronic nonbacterial
      prostatitis.
AB  - Chronic nonbacterial prostatitis is an ill-understood and difficult-to-diagnose
      disease. Symptoms of chronic nonbacterial prostatitis are similar to those of
      chronic prostatitis and include low back pain, frequency, dysuria, perineal
      discomfort, and painful ejaculation. In view of uncertainty about etiology,
      treatment of chronic nonbacterial prostatitis remains speculative. Most treatment
      is aimed at relieving symptoms and not at curing the disease. Because of the
      troublesome nature of chronic nonbacterial prostatitis and the poor results
      obtained from traditional treatment methods, a new modality of transurethral
      microwave hyperthermia was investigated. Six patients were treated from January
      1994 through June 1995 by use of transurethral microwave hyperthermia. These men
      were treated four times during a 2-week period. Their average symptom score
      decrease was 74.9% and was associated with minimal morbidity. Based on this
      result, it is concluded that transurethral microwave hyperthermia is a safe and
      effective treatment modality for chronic nonbacterial prostatitis.

PMID- 9029877
TI  - Anterior hip pain in the adult: an algorithmic approach to diagnosis.
AB  - The adult patient who complains of anterior hip pain is a dilemma frequently
      encountered by the primary care physician. Detailed history taking, physical
      examination, and plain x-ray films are indicated for the initial evaluation.
      Anterior hip pain is often diagnosed as musculoskeletal strain/sprain and treated
      with a conservative regimen represented by the acronym NICER (nonsteroidal anti
      inflammatory drugs, ice, compression, elevation, and rest) with or without
      physical therapy. On occasion, this therapy fails to eradicate the symptoms. When
      these symptoms are refractory to diagnosis by conventional means, a more
      comprehensive evaluation of the etiology is warranted. Refractory pain is defined
      in the authors' practice as pain that persists after 4 weeks of initial
      conservative management. This subsequent evaluation includes the use of such
      laboratory tests as complete blood cell count with differential count, Chem 20
      health profile, erythrocyte sedimentation rate, and an arthritic panel
      (assessment of rheumatoid factor, antinuclear antibody, C-reactive protein).
      Ancillary radiologic tests warranted include a nuclear bone scan, a magnetic
      resonance imaging scan, a computed tomography arthrogram with hip aspiration,
      and/or a scan of white blood cells labeled with indium 111. The test chosen
      depends on the etiology most suspected. A useful diagnostic algorithm for the
      investigation of anterior hip pain in the adult is provided. An illustrative case
      presentation of carcinoma of an unknown primary site presenting as anterior hip
      pain demonstrates the algorithm as it applies in the authors' practice.

PMID- 9029878
TI  - Focal atrophy and cerebrospinal fluid rhinorrhea.
AB  - Focal atrophy is a diagnosis of exclusion in nontraumatic cerebrospinal fluid
      rhinorrhea. It is most commonly associated with ethmoid or sphenoid sinus defects
      and is most prevalent in women between the ages of 30 and 40 years. In the unique
      case described, a 39-year old woman had focal atrophy and cerebrospinal fluid
      rhinorrhea secondary to a sphenoid sinus defect. The defect was diagnosed by
      computed tomography scans and repaired neurosurgically.

PMID- 9029879
TI  - Interferon alfa-associated retinopathy.
AB  - Interferon alfa and its related compounds have been used for more than 10 years
      in the treatment of a number of conditions including viral illnesses, childhood
      hemangiomas, various cancers, and leukemia. The potential applications for this
      class of medication continue to grow. The use of interferon alfa in experimental
      protocols has also increased, thus making it more likely that new indications
      will be discovered. It is probable that primary care physicians will be called on
      to initiate therapy or will see patients being treated with interferon in their
      practice. We report the development of interferon-related retinopathy in a 43
      year-old man while he was receiving experimental treatment with interferon alfa
      for hepatitis B virus and hepatitis C virus infection. The vision loss was acute
      and only partially reversible. Interferon, its mechanism of action, and the past
      literature are briefly discussed.

PMID- 9029880
TI  - Osteopathic physicians and expert medical testimony.
AB  - The US Supreme Court addressed the issue of expert medical and scientific
      testimony in the 1993 case Daubert v Merrell Dow Pharmaceuticals, Inc. The
      guidelines to be used as a standard for expert medical witnesses under Daubert
      differ from earlier standards used by many courts for more than 70 years. This
      commentary reviews the history of previous and current standards used to
      determine admissibility of medical testimony in legal proceedings and discusses
      the ramifications of these standards for osteopathic physicians involved in the
      medical malpractice process.

PMID- 9029882
TI  - Violence in the workplace.

PMID- 9029881
TI  - 'Bridge' between knowledge and practice in diagnosing depression.
AB  - Depression is one of the most common disorders in primary care patients. Yet,
      physicians fail to recognize it in most patients. One of the likely reasons for
      this problem may be that medical students and physicians have difficulty
      recalling pertinent psychiatric didactic information in a clinically usable form.
      To that end, the author presents three mnemonics as a means to help clinicians
      easily recall the information important to making an accurate diagnosis of
      depression in their patients.

PMID- 9029883
TI  - Medical care at the 1996 Olympic Village.

PMID- 9029884
TI  - Doping control in the '96 Olympics.

PMID- 9029885
TI  - The Olympics in Columbus: a first and a legacy.

PMID- 9029886
TI  - The Centennial Olympic Park bombing: Grady's response.

PMID- 9029887
TI  - Gender verification at the centennial Olympic games.

PMID- 9029888
TI  - Olympic fatigue syndrome.

PMID- 9029889
TI  - Paralympics--a triumph for people with physical disabilities.

PMID- 9029890
TI  - Survival of carcinoma of the prostate patients less than 55 years old compared to
      older patient groups.
AB  - Both incidence and death rate from cancer of prostate are rising. Prostate cancer
      is the most common malignancy in man and second most common cause of death in
      men. Lung cancer is the leading cause of death in men. Carcinoma of prostate is
      generally a disease of older men. Carcinoma of prostate can also occur in the
      middle-aged men. This study was performed to find whether the middle-aged men
      survived longer than older men when both groups of patients were compared
      according to equivalent stage of the disease. In this series, survival is
      slightly better in younger age groups when patients of all stages are pooled
      together. Due to small number of patients in younger age groups, survival
      difference cannot be calculated for each stage of the disease.

PMID- 9029891
TI  - Case records of the Department of Medicine University of Mississippi Medical
      Center. Multiple myeloma with a plasmacytoma of the lung.

PMID- 9029892
TI  - Foundation project promotes stroke prevention.

PMID- 9029893
TI  - Lack of immunoreactivity for myoglobin in skeletal muscle of acute stroke
      patients.
AB  - Sternothyroid muscle biopsy specimens, obtained during tracheostomies from 15
      patients with acute stroke and respiratory failure, were examined
      immunohistochemically to immunoreactivity to myoglobin (Mb). A marked decrease or
      lack of Mb immunoreactivity in association with hyaline degeneration was observed
      in 0.8 to 44.4% of the muscle fibers on both the paretic and non-paretic sides of
      all patients. The percentages of negative staining for Mb were less than 3.1% in
      5 patients with acute respiratory failure due to causes other than stroke. The
      pattern and incidence of attenuated Mb immunoreactivity in the muscle fibers was
      found to be distinctively different in the two patients groups. In one group of 5
      patients, a large number of muscle fibers (24.8 +/- 15.6%) had no Mb staining and
      were clearly bordered and grouped. In another 10-patient group, only a limited
      number of muscle fibers (3.3 +/- 2.5%) had no staining for Mb and these fibers
      were scattered. Four patients in the former group had catastrophic outcomes,
      while all the patients in the latter group survived. Ischemia, produced by an
      increase in catecholamines, and the consequent vasoconstriction, rather than
      hypoxemia seemed to be the cause of the negative immunoreactivity for Mb in the
      group pattern. In contrast, hypoxemia may have caused the scattered pattern of
      negative Mb immunoreactivity. It was concluded that negative immunostaining for
      Mb in muscle fibers represents a common and characteristic complication in acute
      stroke patients.

PMID- 9029894
TI  - Petechial hemorrhage of the conjunctiva and histological findings of the lung and
      pancreas in infantile asphyxia--evaluation of 85 cases.
AB  - Eighty-five cases of infantile asphyxia were examined in relation to the degree
      of conjunctivae petechial hemorrhages and histological and immunohistochemical
      findings of the lungs and the pancreas. In very young cases, even in the
      strangulation cases, conjunctivae petechial hemorrhages were unremarkable and
      sometimes absent. The lungs showed remarkable to moderate congestion, while the
      pancreas showed only slight to moderate edema and cell infiltrations. Many
      pancreata of cases of accidental and homicidal asphyxia had hyperplasia and
      nesidioblastosis of islet cells. In adult asphyxia cases, remarkable congestion
      has been the main finding in the lungs and the pancreas. This study shows many
      similarities between the findings in homicidal suffocation and in genuinely
      accidental suffocation, both in inspection and on histological examination. So,
      we here, stressed on the necessity of legal necropsy for various infantile
      asphyxia cases, in the speculation of the cause of death, in order to not only
      study infantile sudden death cause but also not to mis-diagnose genuine
      accidental asphyxia cases or homicidal cases using suffocation for Sudden Infant
      Death Syndrome (SIDS).

PMID- 9029895
TI  - Remnant-stump gastric cancer following partial gastrectomy-clinicopathological
      studies.
AB  - Forty-five cases of remnant-stump (R-S) gastric cancer were investigated
      retrospectively, comparing those which were initially benign (Group 1: 31 cases)
      with those which were initially malignant (Group 2: 14 cases). The incidence of R
      S gastric cancer over all gastrectomy cases from 1967 to 1994 was 1.4%
      (45/3,282). The mean period until development of the R-S gastric cancer following
      partial gastrectomy was 21.6 years in Group 1 and was 15.8 years in Group 2 (p <
      0.05). Of those R-S cases that underwent resection, total gastrectomy was
      selected for 82% in Group 1 and for 85% in Group 2. The incidence of negative
      lymph nodes was only 25% in Group 1 and 62% in Group 2 (p < 0.05). The
      pathological stage I was 21% in Group 1 and 54% in Group 2 (p < 0.05). The 5-year
      survival rate was 32% in Group 1 and was 62% in Group 2 (p < 0.05). To improve
      the prognosis for R-S gastric cancer, periodic endoscopic follow-up examinations
      to find any R-S cancer at the earliest stage is most important, especially in
      cases of a partial gastrectomy for an initially benign case.

PMID- 9029896
TI  - Pulmonary capacity in lung cancer patients prior to lung resection--comparison of
      the unilateral pulmonary artery occlusion test with expired gas analysis during
      exercise testing.
AB  - We attempted to determine if expired gas analysis during exercise testing has
      equal value to the unilateral pulmonary artery occlusion test (UPAO). Sixty-four
      lung cancer patients were evaluated. We performed UPAO and measured mean
      pulmonary artery pressure (PPA) and cardiac output (C.O.) 15 min later, and
      calculated total pulmonary vascular resistance (TPVR). Expired gas analysis
      during exercise testing was performed, and the maximum oxygen consumption per
      unit body surface area (VO2max/m2) and the anaerobic threshold (AT/m2) were
      calculated. The patients were divided into two groups according to the PPA as
      follows: Group PPA(L) and Group PPA(H), and the TPVR as follows: Group TPVR(L)
      and Group TPVR(H). Comparative studies of the mean values of VO2max/m2 and AT/m2
      were performed between the two groups. VO2max/m2 was significantly higher in
      Group PPA(L) than in Group PPA(H). VO2max/m2 was significantly higher in Group
      TPVR(L) than in Group TPVR(H). TPVR and VO2max/m2 showed no significant
      correlation, but a weak negative quadratic correlation with the equation y = 2276
      246.6 logx was found. This result led a minimal acceptable levels for lung
      resection of Vo2max/m2 of 650 ml/min/m2 corresponding to the TPVR levels of 700
      dyne.sec.cm5/m2.

PMID- 9029897
TI  - Neutrophil chemotactic activity in bronchoalveolar lavage fluid recovered from
      patients with diffuse panbronchiolitis.
AB  - The present study was aimed at elucidating the role of inflammatory cells in the
      pathogenesis of the chronic inflammatory changes in the bronchioles of patients
      with diffuse panbronchiolitis (DPB) and at determining the mechanism for the
      clinical efficacy of erythromycin (EM) therapy for these patients. For this
      purpose, neutrophil percentages, neutrophil chemotactic activity (NCA), IL-8 and
      TNF-alpha in the bronchoalveolar lavage fluid (BALF) were measured in 9 patients
      with DPB. Significantly higher neutrophil percentages, NCA and IL-8
      concentrations were demonstrated in the BALF from DPB patients than from chronic
      bronchitis (CB) patients or healthy control subjects. The levels of these
      indicators of chronic inflammation in the BALF from DPB patients were
      significantly decreased after EM therapy. TNF-alpha was elevated in the BALF from
      both DPB- and CB-patients and was not decreased by treatment of the DPB patients
      with EM. From the above results, it can be concluded that IL-8, not TNF-alpha, is
      the major chemoattractant for neutrophils and that the inhibition of IL-8
      production by EM induces the subsequent depression of neutrophil accumulation in
      the peripheral airways, and consequently, prevents the peripheral airway tissue
      damage due to accumulated and activated neutrophils.

PMID- 9029898
TI  - Mucinous adenocarcinoma of the stomach-clinicopathological studies.
AB  - The clinical and morphological features of 58 cases of the rare mucinous
      adenocarcinoma of the stomach (MUC) were investigated and compared to those of
      other pathological types. The incidence of MUC was only 2.9% of all cases of
      resected gastric cancer. Among the 58 cases of MUC, the incidence of early cases
      was only 19% (Group 1), while among other pathological types of cancer, it was
      42% (Group 2) (p < 0.001). The incidence of early mucosal cancer was 0% in Group
      1, and 54% in Group 2 of the resected early gastric cancer. The incidence of
      lymph node metastasis rate was 81% in Group 1, and was 46% in Group 2 (p <
      0.001). The presence of peritoneal dissemination was 21% in Group 1, and was 8%
      in Group 2 (p < 0.001). The incidence of liver metastasis pre- and
      intraoperatively was 0% in Group 1, and was 3.5% in Group 2. The overall 5-year
      survival rate was 45% in Group 1, and was 61% in Group 2 (p < 0.05). In stage
      III, the 5-year-survival rate was 30% in Group 1, and was 49% in Group 2 (p <
      0.05). There was no statistical prognostic difference between the two groups in
      stage I, II and stage IV. Therefore, to improve the outcome for MUC, more
      effective radical gastrectomy and aggressive immunochemotherapy should be
      selected especially for stage III mucinous adenocarcinoma of the stomach.

PMID- 9029899
TI  - Changes of vasoactive peptides and effects of inhaled nitric oxide after
      pneumonectomy.
AB  - To clarify the role of vasoactive peptides in the physiologic response to
      pneumonectomy, we investigated the changes of atrial (A-type) natriuretic peptide
      (ANP). C-type natriuretic peptide (CNP), and endothelin-1 (ET-1) levels in the
      lung and blood after pneumonectomy and the effects of inhaled nitric oxide (NO; 5
      ppm) after pneumonectomy in beagle dogs. The concentrations of these peptides in
      the lung and blood were measured by radioimmunoassay. The dogs in group A (n =
      10) were observed without NO inhaling after right pneumonectomy, and the dogs in
      group B (n = 5) were observed with NO inhaling from 120 to 180 min after right
      pneumonectomy. After the thoracotomy, right lung tissue was resected for the pre
      operative histological control. Tissue from the left lung was obtained at 120 min
      (5 dogs in group A), at 180 min (5 dogs in group A), and after 60 min of NO
      inhalation (group B) for the post-operative histological material. Peripheral
      blood was collected from the femoral artery. The pulmonary arterial pressure
      (PAP) was significantly increased after pneumonectomy, but rapidly decreased to
      the same level as the pre-operative stage after NO inhalation. Increases of
      plasma ANP, lung ANP and lung CNP levels occurred after pneumonectomy, while the
      ET-1 level was unchanged. Inhaled NO rapidly reduced the plasma ANP, lung ANP and
      lung CNP. These results indicate that both ANP and CNP act to maintain
      normotensive homeostatic balance in the pulmonary circulation.

PMID- 9029900
TI  - Analysis of sleep EEGs by the interval histogram method--validity of the baseline
      night as a control and the effect of ethyl loflazepate (CM6912).
AB  - The effects of an anxiolytic drug, ethyl loflazepate (CM6912) on sleep EEGs were
      investigated by the interval histogram method originally developed. EEGs were
      classified into each of the delta 2-beta 2 and sigma 1 wave-form parameters, and
      the individual frequencies were determined on the third baseline, second drug and
      the first recovery nights in each sleep stage. In comparison with the second
      baseline night, the sigma 1 waves in stage 2 sleep and the delta 1 waves in REM
      sleep were decreased and the alpha and sigma 1 waves in stage 3 sleep were
      increased on the third baseline night. In consideration of the 5% significance
      level and the remarkable influence of drug administration, described below, no
      major problems were encountered in the use of the night as a control in this
      experimental schedule. The main characteristics of administration of CM6912
      manifested as decreases in the slow wave, increases in the fast wave, and an
      increase in the sigma 1 wave in sleep stages other than stage 1. These tendencies
      were remarkable on the second drug night and were still evident even on the
      recovery night. Increases in sigma 1 wave were related to increases in sleep
      spindles. The increases in the beta 2 wave were particularly remarkable in REM
      sleep.

PMID- 9029901
TI  - Cloning and expression of cDNA for soluble form of rat heme oxygenase-1.
AB  - Heme oxygenase catalyzes the oxidation of heme to biliverdin and carbon monoxide.
      The gene encoding the truncated soluble rat heme oxygenase-1 (Metl-Pro267) was
      cloned. The enzyme protein was expressed in E. coli JM109 and purified to
      homogeneity. The molecular weight of the recombinant enzyme was 30 kDa as
      assessed by SDS-polyacrylamide gel electrophoresis. From a 3-L culture, about 90
      mg of the purified enzyme was routinely obtained. The dependency of the heme
      oxygenase reaction catalyzed by the soluble enzyme on the NADPH-cytochrome P-450
      reductase concentrations and the effect of catalase on the reaction were examined
      to compare with the purified membrane-bound form of heme oxygenase-1 (Yoshida and
      Kikuchi, 1978b). The activity of the soluble enzyme was inhibited at high
      concentrations of NADPH-cytochrome P-450 reductase and the inhibition was not
      alleviated by addition of catalase unlike the membrane-bound form. The ferric
      iron of the heme-heme oxygenase complex was in a typical high spin state at
      acidic to neutral pH (pH 6.5-7.0) but conversion to low spin state was observed
      at basic pH (pH 9-10). The heme bound to heme oxygenase was converted to
      biliverdin at a stoichiometric ratio of unity in the presence of NADPH-cytochrome
      P-450 reductase system. During the heme degradation of the heme-heme oxygenase
      complex under atmospheric oxygen, several intermediates, that is, oxygenated heme
      and verdoheme, were spectrally discriminated.

PMID- 9029902
TI  - A pylorus-retaining pancreatic head-duodenectomy for cancers of the duodenal
      papilla and the lower bile duct.
AB  - With the development of diagnostic technology, the surgical methods of cancer
      therapy have been expanded, and operations have been performed using a procedure
      corresponding to the stage of cancer to improve the postoperative QOL. A 79-year
      old man with cancer of the duodenal papilla and obstructive jaundice, and a 63
      year-old woman with cholangiocarcinoma in the lower region complicated by
      cholangitis caused by Candida underwent resections of the pancreatic head and
      duodenum, and pancreaticogastrostomies retaining the pylorus. Satisfactory
      results were obtained in both cases. The merits of the procedure were that there
      were few complaints, sufficient food could be ingested and the QCL was
      maintained. The benefits of pancreaticogastrostomy are that the anastomosis
      procedure is simple, the gastric wall is thicker than the jejunum and blood flow
      is plentiful. The dorsal gastric wall is located close to the pancreatic cut-end,
      therefore tension is not created, and the pancreatic enzymes are not activated
      because the anastomosis site does not contact the intestinal fluid. These
      characteristics should decrease the rate of anastomosis failure which can be a
      fetal complication. A safer operation is desirable, particularly for elderly
      patients or patients who have complications.

PMID- 9029903
TI  - Dead but not deserted. Retrospective diagnosis: the potential and the pitfalls.

PMID- 9029904
TI  - Is Hippocrates dead yet?

PMID- 9029905
TI  - Overview of implantable cardioverter-defibrillator in reducing total mortality in
      the high-risk coronary patient.
AB  - The idea of an implantable cardioverter-defibrillator (ICD) was conceived in the
      mid- to late 1960s, and working circuits were built and tested at Sinai Hospital
      of Baltimore in the fall of 1969. After a number of years of preclinical testing,
      the device entered clinical trials at The Johns Hopkins Hospital in February,
      1980, and received Food and Drug Administration (FDA) approval in 1985. The
      device appeared to be highly effective, but there was criticism that it had not
      been tested in a randomized fashion, and there was the feeling that drugs would
      eventually prove to be superior. In 1989, a series of randomized clinical trials
      were begun. One of these trials, the Multicenter Automatic Defibrillator
      Implantation Trial (MADIT), has concluded and the outcome has recently been
      published. The results are landmark in importance and lead the way towards
      rational treatment of serious ventricular arrhythmia patients in clinical
      practice.

PMID- 9029906
TI  - Incidental detection of cystic neoplasms of the pancreas.
AB  - Cystic neoplasms of the pancreas are rare, accounting for less than 1% of all
      pancreatic tumors Since the advent of computerized tomography (CT), an increasing
      number of these lesions are being discovered incidentally. Compagno and Oertel
      were the first to thoroughly describe and differentiate the benign serous
      cystadenoma from the potentially or overtly malignant mucinous
      cystadenoma/cystadenocarcinoma spectrum. At present, our ability to definitively
      differentiate between these two classes of cystic neoplasms is limited. Because
      of this, controversy exists as to their appropriate surgical management. A case
      report is presented and followed by a review of the literature on incidentally
      detected cystic neoplasms of the pancreas.

PMID- 9029907
TI  - Spontaneous mediastinal hemorrhage: a case report with a review of the
      literature.
AB  - A patient on chronic hemodialysis presenting with shortness of breath and
      dysphagia was found to have massive hemomediastinum. A review of the world's
      literature prompted by this case reveals that this rare entity can be classified
      into three general groups: (1) hemomediastinum secondary to underlying bleeding
      disorder, (2) hemomediastinum secondary to hemorrhage into a mediastinal organ or
      gland, without underlying bleeding disorder and (3) idiopathic hemomediastinum,
      without underlying bleeding disorder. Therapy depends upon the underlying
      etiology and the severity of symptoms.

PMID- 9029908
TI  - 46,XY,i(21q) identified by maternal serum screening.
AB  - Maternal serum screening for the detection of fetal Down syndrome has become
      widespread. Prenatal detection of fetal Down syndrome has important implications
      not only for management of the current pregnancy, but also for recurrence risk
      counseling for future pregnancies. We report a case of fetal Down syndrome due to
      an isochromosome 21q detected after maternal serum screening using alpha
      fetoprotein and human chorionic gonadotropin indicated an increased risk for
      fetal Down syndrome in a 19-year-old pregnant woman. This confirms that maternal
      serum screening can detect fetal Down syndrome due to rare chromosome
      rearrangements and illustrates the importance of cytogenetic studies for
      provision of appropriate genetic counseling.

PMID- 9029909
TI  - Managed care and the physician-patient relationship: implications for peer
      review.

PMID- 9029910
TI  - Lotka-Volterra representation of general nonlinear systems.
AB  - In this article we elaborate on the structure of the generalized Lotka-Volterra
      (GLV) form for nonlinear differential equations. We discuss here the algebraic
      properties of the GLV family, such as the invariance under quasimonomial
      transformations and the underlying structure of classes of equivalence. Each
      class possesses a unique representative under the classical quadratic Lotka
      Volterra form. We show how other standard modeling forms of biological interest,
      such as S-systems or mass-action systems, are naturally embedded into the GLV
      form, which thus provides a formal framework for their comparison and for the
      establishment of transformation rules. We also focus on the issue of recasting of
      general nonlinear systems into the GLV format. We present a procedure for doing
      so and point at possible sources of ambiguity that could make the resulting Lotka
      Volterra system dependent on the path followed. We then provide some general
      theorems that define the operational and algorithmic framework in which this is
      not the case.

PMID- 9029911
TI  - Autocatalytic networks with intermediates. I: Irreversible reactions.
AB  - A class of autocatalytic reaction networks based on template-dependent
      replication and specific catalysis is considered. Trimolecular "elementary steps"
      of simple replicator dynamics are resolved into two consecutive irreversible
      reactions. The extreme cases, competition for common resources and hypercycle
      like cooperative feedback, were analyzed in some detail. Although the dynamics of
      the extended networks resembles corresponding replicator dynamics in general,
      there are significant differences. Most notably, the interior fixed points in the
      cooperative model turned out to be asymptotically stable for an arbitrary number
      of species, whereas simple replicator dynamic predicts an asymptotically stable
      periodic orbit fixed for four species and fewer and a stable periodic orbit for
      all other cases.

PMID- 9029912
TI  - Personal liberties versus public safety: some issues for mental health review
      tribunals (MHRTs)

PMID- 9029913
TI  - Myocarditis misdiagnosed as sudden infant death syndrome (SIDS).
AB  - In a retrospective study spanning five years, the histologic sections of 35
      autopsies of infants diagnosed as SIDS victims were reviewed. Based on a recently
      reported study in which findings on marked basement membrane thickening (BMT) in
      the true vocal cords was suggested as a pathognomonic marker of SIDS, we expected
      to find BMT in all these cases. However, in seven of the reviewed autopsies (20%)
      no BMT was detected. Examination of new histologic sections of all the victims
      revealed myocarditis in these seven cases. In a control group (n = 18) of
      children with known cause of death, neither BMT nor myocarditis were found. The
      incidence of myocardial diseases in infants and young adults (20% and 22%
      respectively) reported in the literature indicates that myocarditis is not a rare
      cause of sudden death in infants. Therefore, in SIDS-suspected cases a meticulous
      post-mortem microscopic examination of the heart should be carried out,
      especially whenever BMT of the vocal cords is absent.

PMID- 9029914
TI  - Comparison of wound patterns in homicide and dyadic death.
AB  - A comparison of patterns of injuries between homicides and cases of dyadic death
      was performed. In 195 homicides, 139 deceased (71%) showed exclusively one type
      of trauma (mainly gunshot wounds) whereas two and even three types of trauma were
      detectable in 45 (23%) and 11 (6%) of the cases, respectively. In contrast, 18
      out of 20 victims of dyadic death (90%) showed one type of injury (mainly gunshot
      wounds) and only two victims showed two types of injury. Even though different
      methods of killing seem to be unusual in dyadic death, even in cases with more
      than one victim and evidence of different types of injuries, such features cannot
      provide reliable information useful for a differentiation between homicide and
      extended suicide.

PMID- 9029915
TI  - Diseases of the airways and lungs in forensic autopsy material of alcoholics.
AB  - The frequency of diseases of the airways and lungs was examined in a forensic
      autopsy material of 441 alcoholics, who were compared with 255 controls. Lobar
      pneumonia was seen only in alcoholics, emphasizing alcohol abuse as a
      predisposing factor for this infection. Tuberculosis was more frequent in
      alcoholics, while there were no major differences in the occurrence of chronic
      lung diseases.

PMID- 9029916
TI  - Judicial problems related to transsexualism in France.
AB  - The French courts have recently changed their juridical position about
      transsexualism. The new decisions have, among other things, asserted the
      necessity for preliminary judicial expertise, an ordinary medical report not
      being satisfactory as a legal basis. The authors present a summary of the
      juridical evolution, an expert analysis of transsexualism and the key concepts
      that the experts will have to debate.

PMID- 9029917
TI  - Does being unusual and dangerous mean you are mad?
AB  - This article is, essentially, an examination of what the medical profession and
      society generally mean by the term 'mad', and what relevance 'madness' has to
      modern psychiatry. It suggests that 'madness' differs from 'mental illness' and
      that psychiatry only deals with the latter. It concludes that for any rigorous,
      rational approach to psychiatry to be attempted an accepted framework of what
      constitutes mental illness must be used. This is the important role of ICD 10 and
      DSM IV which help to ensure that psychiatrists do not act as 'moral gaolers of
      the state'.

PMID- 9029918
TI  - Dirty protests: a phenomenological assessment.
AB  - The use of faecal material as a means to effect a personal protest appears to be
      a behaviour restricted to prison establishments. Over the last decade, this form
      of protest appears to be diminishing. Dirty protests are described, and possible
      aetiologies explored.

PMID- 9029919
TI  - A survey of sentenced prisoners transferred to hospital for urgent psychiatric
      treatment over a three-year period in one region.
AB  - This study describes a survey of sentenced prisoners who were transferred to
      psychiatric hospitals in South Wales under 8.47 of the Mental Health Act of 1983
      (England & Wales) over a three-year period. During this time there were 29 such
      transfers of 25 prisoners and all were male. Fifty per cent of these prisoners
      who became patients had a clinical diagnosis of schizophrenia, 13 per cent of
      recurrent depressive disorder, 4 per cent of a drug-induced psychosis, 4 per cent
      of hypomania and 6.6 per cent had some form of personality disorder. Forty-four
      per cent were returned to prison to complete their sentence once their mental
      disorder was treated.

PMID- 9029920
TI  - The use of health legislation to deal with abuse of community based elderly
      people with dementia.
AB  - This paper describes current health legislation used to deal with actual and
      potential abuse of elderly people with dementia living in the community. Recent
      recommendations made regarding updating existing legal processes and creating new
      provisions are also outlined.

PMID- 9029921
TI  - A prospective study of assaults on staff by psychiatric in-patients.
AB  - This study determined the prevalence and features of assaults on staff, compared
      them with other aggressive incidents by psychiatric in-patients, and studied
      their relationship with the ward atmosphere. There were 181 physical assaults
      among 279 staff in two months, i.e. 389 assaults per 100 staff per year. A few
      patients were responsible for the majority of the assaults. Most assaults were
      triggered off by staff-patient interaction. About one-third of the staff were
      significantly psychologically shaken by the incidents. Patients were more likely
      to be provoked and used more severe means of aggression against staff than
      against other targets of aggression. There were no significant differences
      between the characteristics of patients who assaulted staff and those who had
      other targets of aggression.

PMID- 9029922
TI  - Inadequacies in the Mental Health Act, 1983 in relation to mentally disordered
      remand prisoners.
AB  - There are widely recognized problems regarding access to NHS facilities for
      mentally disordered remand prisoners (Robertson et al., 1994). The Bentham Unit
      was set up in February 1994 to provide the earliest possible hospital admission
      for mentally disordered remand prisoners. Over the first twelve months of the
      service's operation we assessed 150 and admitted 62 remand prisoners: a full
      description of the service is in preparation. Because admission is restricted to
      remand prisoners, the inadequacies of current legislation in allowing effective,
      uninterrupted care for remand transfers have become very apparent. There have
      been recent proposals to review the 1983 Mental Health Act (Murphy, 1995) and we
      suggest that provisions for assessment and treatment of mentally disordered
      remand prisoners should be revised in this context.

PMID- 9029923
TI  - The Mental Health Act and professional hostage taking.
AB  - Compulsory detention of psychiatric patients is seen as a necessary response to a
      perceived threat, against themselves or against others, and such detention is
      rationalized as humane, compassionate and benevolent. However, seen from the
      recipient's perspective such detention and enforced treatment may be viewed as
      malevolent. This paper is concerned with examining the role of compulsory
      detention of the mentally abnormal offender in respect of the 1983 Mental Health
      Act by analysis of the resultant ideas which underpin it. First, in terms of its
      role as a sanction against transgressors of a particular value system, who are
      spotlighted by the increased 'surveillance' in our society. Second, the issues of
      treatability and consent are discussed in relation to the neo-legalism that
      permeates our social world. In addition, the role of the 1983 Mental Health Act
      as a means of social control will be examined using the notion of a covert
      political 'policing' in the form of compulsory detention, resulting from the
      medico-legal confrontation of power bases which defines the patient as a
      'professional hostage'. Quite clearly there is an overlap of themes which creates
      a difficulty in interpretation. However, with increasing legal facilities for
      detention and the increasing number of 'conditions' being drawn under the medical
      umbrella it is important to attempt to review the results of this legislation
      within those areas identified above and to understand how this may be interpreted
      for those held against their wishes.

PMID- 9029924
TI  - A prospective study of coroner's autopsies in University College Hospital,
      Ibadan, Nigeria.
AB  - The present study reviews 876 consecutive coroner's autopsies performed in the
      Department of Pathology, University College Hospital, Ibadan over a two-year
      period (1 February 1991 to 31 January 1993). The hospital autopsy rate during the
      study period was 36.2%, and 62.5 per cent of these post-mortems were medico-legal
      cases. The most common indications for coroner's autopsies were sudden natural
      deaths (55.6%), followed by accidental deaths (35.3%). The proportions of
      maternal (4.3%), homicidal (3.1%) and suicidal (0.3%) deaths were much lower. The
      male to female ratio was 1.7 to 1. Ninety-one (10.4%) of the cases fell within
      the paediatric age group and the peak age incidence for these cases was in the 5
      14 years age group. The remaining 785 (89.6%) cases were adults and the peak age
      incidence for these cases was in the fourth decade of life. The most common cause
      of sudden natural death was cardiovascular disease, of which hypertension
      constituted the majority of cases. Other major causes of sudden death included
      pneumonia, meningitis, typhoid fever and neoplastic diseases. Road traffic
      accidents accounted for 78 per cent of accidental deaths followed by falls
      (13.3%) and burns (4.6%). Abortions, post-partum haemorrhage and eclampsia were
      the major causes of maternal deaths in the present study. Homicidal deaths were
      eight times more frequent in male than female victims and the commonest mode of
      death was gunshot injuries. Suicidal deaths remain extremely uncommon in African
      patients, as confirmed by our study.

PMID- 9029925
TI  - Sudden death due to cardiac myxoma.
AB  - Primary tumours of the heart are rare, their incidence ranging from 0.0017 to
      0.28 per cent in various autopsy series (Colucci and Braunwald, 1992). Thirty per
      cent of these tumours are cardiac myxomas (McAllister and Fenaglio, 1978). The
      latter are histologically benign but potentially lethal. Sudden death is reported
      in 15 per cent of cases and is mainly attributed to massive embolism or
      mechanical interference to blood flow within the heart by the tumour (Fisher,
      1983). This incidence could be due to the absence of clinical manifestations of
      the disease or to the presence of non-specific or subtle ones that preclude early
      referral for specialist evaluation (Colucci and Braunwald, 1992). Such a poor
      prognosis is not altogether justified, however, considering the highly sensitive
      and accurate diagnostic techniques and the level of surgical treatment which can
      be offered today (Larsson et al., 1989; Roberts, 1989; Bortolloti et al., 1990;
      Lyons et al., 1991). We present a case diagnosed at post-mortem of an atrial
      myxoma which had subtle ante-mortem manifestations. This paper should alert the
      clinician with regard to the need to be aware of the rather obscure clinical
      presentation which may accompany this potentially treatable condition.

PMID- 9029926
TI  - A post-mortem examination was NOT done through a large autopsy incision.

PMID- 9029928
TI  - Decapitation--a rare complication in hanging.
AB  - Decapitation from hanging is rare and there appears to be a lack of reports in
      scientific literature. Two cases of this phenomenon are reported.

PMID- 9029927
TI  - The obscure autopsy and neuroleptic malignant syndrome.
AB  - The technique of immunocytochemistry was used to identify myoglobin in kidney,
      confirming a diagnosis of neuroleptic malignant syndrome following an otherwise
      obscure autopsy in a decomposed body. The features of neuroleptic malignant
      syndrome are reviewed with a differential diagnosis of myoglobin renal casts. The
      report emphasizes a thorough and detailed assessment of deaths which occur during
      treatment with neuroleptic drugs.

PMID- 9029930
TI  - When a 'match' is not a genetic match.

PMID- 9029929
TI  - Oncocytic cardiomyopathy: a rare cause of unexpected early childhood death
      associated with fitting.
AB  - A 15-month-old girl died unexpectedly in hospital following a five-day history of
      intermittent cardiac arrhythmias and convulsions preceded by several weeks of
      occasional vomiting. Autopsy revealed subendocardial nodules in the left
      ventricle, and tricuspid and mitral valves that were composed of aggregated large
      cells with foamy, pale pink cytoplasm characteristic of oncocytic cardiomyopathy.
      Fat stains were positive for neutral lipid and phospholipid and electron
      microscopic examination revealed numerous irregular mitochondria within affected
      cells. Examination of the brain revealed no structural or histologic
      abnormalities, anoxic damage or thromboembolic material. Oncocytic
      cardiomyopathy, though rare, may cause unexpected death in previously well young
      children with quite variable preceding clinical symptoms and signs which include
      fitting. Although the aetiology is unknown there is evidence that mitochondrial
      dysfunction may be involved.

PMID- 9029931
TI  - Nonfebrile seizures.

PMID- 9029932
TI  - Tuberculosis: an update.

PMID- 9029933
TI  - Treatment of adrenocortical insufficiency.

PMID- 9029934
TI  - Index of Suspicion. Case 1. Dystonic reaction to metoclopramide.

PMID- 9029935
TI  - Index of Suspicion. Case 2. Pseudoparalysis of Parrot caused by congenital
      syphilis.

PMID- 9029936
TI  - Index of Suspicion. Case 3. Bronchiolitis and diabetic ketoacidosis.

PMID- 9029937
TI  - Complications of immunizations.

PMID- 9029938
TI  - The nutritional adequacy of mineral content of formulas.
AB  - The nutritional adequacy of infant formulas is a subject with which all
      pediatricians need to be familiar. Unfortunately, we are still learning what is
      nutritionally adequate and what is excessive for some minerals in infants.
      Pediatricians must be aware of the parameters that are used when such
      recommendations are made. Although this brief does not contain an analysis of
      each individual formula, the commercial infant formulas currently in use provide
      an adequate intake of the minerals through the first 6 months of life.
      Thereafter, supplementation with solid foods is suggested.

PMID- 9029939
TI  - Acyclovir.

PMID- 9029940
TI  - Structural and functional diversity in the leucine-rich repeat family of
      proteins.

PMID- 9029941
TI  - Development and applications of in vivo clinical magnetic resonance spectroscopy.
AB  - 4.1 CURRENT STATUS. While an extensive clinical literature of MRS of muscle,
      brain, heart and liver has been achieved, the MRS technique is not considered
      essential for routine diagnosis because it is inherently insensitive and
      metabolic changes tend to be small. However, MRS techniques have proven to be of
      considerable value for prognosis in some circumstances, notably for predicting
      outcome following hypoxic-ischaemic injury in the newborn and also in predicting
      graft viability following organ transplantation. The chemical specificity of MRS
      has been illustrated, and exploiting the non-invasive nature of the technique,
      metabolic fingerprinting of pathophysiological processes throughout the natural
      history of a wide variety of diseases is now being accomplished. Particularly
      exciting are the applications of 13C MRS for measuring hepatic and muscle
      glycogen levels, for example in diabetics, and the use of hepatic 31P MRS for
      assessing liver function in cirrhosis. Other areas of excitement are the
      applications of 1H MRS in assessing neuronal function in epilepsy and stroke, and
      for measuring the evolution of lactate in stroke and hypoxic-ischaemic
      encephalopathy. Emphasis on technique development continues, and applications
      still tend to be technology-led. The availability of routine clinical MRI systems
      with spectroscopy capabilities has given MRS studies wider applicability. The
      recent improvements in spatial resolution have been impressive and the technique
      is slowly becoming more quantitative. 4.2. FUTURE PERSPECTIVES. Given the
      flexibility of clinical magnetic resonance techniques, particularly magnetic
      resonance imaging, it is likely that MRI will be the diagnostic tool of choice in
      a wider range of diseases, such as multiple sclerosis, stroke, neurodegenerative
      conditions, sports injuries and in staging malignancies. Since proton magnetic
      resonance spectroscopy packages have become a routine addition to many MRI
      systems, it is feasible to select the MRI sequences of most value in highlighting
      anatomical and pathological abnormalities and to incorporate specifically
      selected MRS sequences to emphasize biochemical differences. Improvements in
      technical methodologies are central to further developments. For example, use of
      internal coils, such as implantable or endoscopic coils, will enable small
      regions of tissue to be studied in considerable detail, which may otherwise be
      inaccessible to measurement. Chemical MRS studies have benefited from the use of
      higher magnetic fields, and the same may be expected for clinical MRS studies.
      Whole-body magnets up to 4 T have been used in a few centres, and certainly 3 T
      systems are becoming more widely available with the recent tremendous interest in
      functional imaging. Certainly, better control of artefacts can be expected; for
      example, improved definition of spectral changes due to voluntary or involuntary
      movements. Wider use of proton decoupling methods will improve the specificity of
      the spectra, by allowing definitive assignments of overlapping resonances, as
      well as the sensitivity. Comparing PET and MRS studies, it is becoming
      increasingly obvious that both will be required in parallel to explore parameters
      of brain metabolism and function. The ability to measure 13C MR signals in the
      brain has been demonstrated, which allows measurements of glutamate and glucose
      turnover. MRS measurements have the advantage of not requiring a radioactive
      isotope, as well as being insensitive to activity-related changes in regional
      cerebral blood flow. Also the study of cerebral glucose metabolism by MRS is very
      promising, allowing a resolution and sensitivity comparable to PET. A combination
      of MRS and PET studies will allow the pathogenesis of neuropsychiatric disorders
      to be better understood. (ABSTRACT TRUNCATED)

PMID- 9029942
TI  - Crystalline bacterial cell surface layers (S-layers): from cell structure to
      biomimetics.

PMID- 9029943
TI  - Structure and function of the WW domain.

PMID- 9029944
TI  - X-ray computed microtomography (microCT) using synchrotron radiation (SR).

PMID- 9029945
TI  - The psychoanalytic study of the child. Introduction.

PMID- 9029946
TI  - Anna Freud's contributions to our knowledge of child development. An overview.
AB  - Anna Freud's contribution to our understanding of child development, normal and
      abnormal, is so substantial, extensive, diverse, and rich in its implications
      that its summary is beyond the scope of a single presentation. Accordingly this
      paper concentrates on some contributions that have especially influenced the
      author, on later, comparatively neglected writings, and on works that looked at
      what had gone before as well as what lay ahead. But, it is argued, Anna Freud's
      contributions cannot be assessed simply in terms of her writings. The creation of
      the Hampstead Child Therapy Course and Clinic, along with its leadership and the
      stimulation it gave to others both there and world wide, is regarded as her
      greatest achievement.

PMID- 9029947
TI  - Differentiation and integration.
AB  - The purpose of this paper is to propose a clinical approach to coordinating the
      psychoanalytic process with the developmental process in treating children. The
      paper is constructed as a dialogue between the spirit of Anna Freud and myself; a
      vignette brings together the principal traditional features Ms. Freud understood
      as "psychoanalytic" with her innovative propositions about the "developmental."

PMID- 9029948
TI  - Current issues in psychoanalytic child development.
AB  - This paper addresses Anna Freud's propositions about the significance of the
      developmental point of view. Beyond the role of genetic reconstruction, the
      developmental dimension demands our investigation of developmental
      reorganization, which leads to new structures with new priorities and new
      hierarchies. This paper also attempts to explore the difficulties and resistances
      in the path that forwards the developmental point of view. References are made to
      object relations and intersubjectivity theories, which seem to give relatively
      little attention to the structure and the history of pathology. Moreover, we have
      outlined areas of development and maturation that need further investigation in
      order to achieve a better understanding of the complex evolvement of the mind.

PMID- 9029949
TI  - "Put yourself in the skin of the child," she said.
AB  - Two Native American children were adopted by a non-Indian family. Following a
      legal challenge under the provisions of the Indian Child Welfare Act, the case
      became before both the United States Supreme Court and an Indian Tribal Court. In
      this paper we analyze the procedure and outcome of this transcultural adoption
      case from the point of view of the children involved and compare it with the
      intracultural "Baby Richard" case. Anna Freud believed that continuity of care is
      vital for each child's healthy growth and development. Transcultural adoptions
      highlight questions that characterize contested placements, whether or not they
      cross cultural boundaries and whether or not they place children across lines of
      race, color, religion, or national origin.

PMID- 9029950
TI  - Anna Freud as a historian of psychoanalysis.
AB  - This article explores a series of papers Anna Freud wrote in the 1970s, which
      constitute her history of child psychoanalysis. It notes her purposes
      theoretical, clinical, and institutional-for reviewing this history and then
      focuses on three themes that she stressed. First, she emphasized that the
      "widening scope of psychoanalysis" had been both tremendously fruitful and
      perplexing as it revealed areas-such as the developmental pathologies-for which
      theory and technique lag. Second, she underscored the way child analysis had been
      extended from pathology to the theory of normal development, particularly by
      adding child observation to its research methods. Third, she noted how child
      analysis has often been hampered by reductionist thinking, and she made a plea
      for complexity: for considering all metapsychological frameworks and all
      developmental lines, and for articulating a complexly grounded diagnostic.

PMID- 9029951
TI  - Offerings and acceptances. Technique and therapeutic action.
AB  - This paper presents several proposal about clinical psychoanalysis. One proposal
      suggests that an analyst's essential offering is a non-hierarchical partnership
      in discovering. Another implies that a valuable goal of psychoanalytic work is to
      acquire the adaptive tool of "insighting," an acquisition that is promoted by the
      structure of the partnership. The paper contains arguments that support the
      proposals, as well as an extended clinical anecdote that illustrates them.

PMID- 9029952
TI  - Undoing the lag in the technique of conflict and defense analysis.
AB  - When the individual skills of a psychotherapist or psychoanalyst coincide with
      what serves as a sublimation for the practitioner, the gratification in the
      clinical work is especially enhanced. If those moments of applied skill also are
      a part of the specific therapeutic action of that form of treatment, a fortunate
      combination exists. As Freud expanded the potential of psychoanalytic treatment
      when he reformulated the theory of anxiety, he also provided access to improved
      therapeutic actions in the course of analyzing intrapsychic conflict. This meant
      that some of the sublimations in practicing the earlier techniques no longer
      coincided with what could be the therapeutic actions characteristic of the more
      effective analysis of conflict. The lag in adding new technical measures to
      psychoanalytic methodology is more fully accounted for by a reluctance on the
      part of some analysts to sacrifice certain traditional sources of sublimated
      projection in interpretations and to seek other sublimations commensurate with
      Freud's more advanced view of analyzing defenses.

PMID- 9029953
TI  - Dread of the strength of the instincts. A psychoanalytic contribution to the
      understanding of violence.
AB  - Dread of the strength of the instincts develops as an affective state in which
      displacements generally available to an individual have been weakened, rendering
      that person more vulnerable to committing an act of violence. Although the case
      presented here includes an act of violence, ways that this act could have been
      foreseen and thus possibly forestalled through analysis are explored. Factors in
      this child's development are reviewed with regard to their possible predisposing
      contributions.

PMID- 9029954
TI  - Anna Freud and developmental psychoanalytic psychology.
AB  - When reviewed in its entirety, Anna Freud's legacy represents her efforts to
      address the deepest of metapsychological dilemmas: What moves development along,
      and is it inherently progressive and linear? She created a developmental
      psychoanalytic psychology that is remarkably current and draws upon principles of
      neurobiology, genetics, pediatrics, and social psychology. Her general
      developmental psychology builds upon three fundamental notions: (1) development
      proceeds not predominantly stage-based but more continuous and cumulative, with
      progressions and regressions; (2) progression along developmental lines involves
      the maturational push of innate or biologic givens as well as the interaction
      between biology and environmental conditions; and (3) understanding the
      complexities of normal development is a means of understanding the presence or
      absence of psychopathology in any given symptomatic presentation. These
      contributions and the notion of a developmental psychoanalytic psychology are
      reviewed through the contemporary lens of the field of developmental
      psychopathology. The enduring contributions of Anna Freud's developmental
      psychoanalytic psychology to child psychiatry and child development are in asking
      how mind and body are brought together, and in asserting that the interaction
      between the biologic and the mental remains the common ground of all disciplines
      concerned with children.

PMID- 9029955
TI  - Anna Freud. A historical look at her theory and technique of child
      psychoanalysis.
AB  - This paper traces historically the development of Anna Freud's thinking about the
      theory and technique of child psychoanalysis. Representing more than fifty years
      of work, her ideas were refined and many were altered, influenced by naturalistic
      and clinical observations and her developmental viewpoint. The paper begins with
      her 1926 Introductory Lectures, which contain both her early views about the
      technique used with children as compared to adults and the origins of many of her
      later ideas. It follows her theories up through her final papers, published in
      the late 1970s.

PMID- 9029956
TI  - Object relations, affect management, and psychic structure formation. The concept
      of object constancy.
AB  - Object relations are central to contemporary structural theory. This paper first
      reviews the various ways in which the key concept object constancy has been used.
      To reconcile the apparent contradictions in definitions, the concept is viewed
      along a developmental continuum in which each step is defined by its functions.
      It is proposed that at its most mature stage, a capacity for affective self
      regulation is achieved, a capacity that is central to characterological structure
      formation and optimal adaptation. Possible interferences with the achievement of
      mature object constancy are briefly explored.

PMID- 9029957
TI  - Diagnosis in clinical practice. Its relationship to psychoanalytic theory.
AB  - The rapidly growing diversity of psychoanalytic clinical practice calls for a
      reexamination of its relationship to psychoanalytic theory. This is as strikingly
      evident in the field of diagnosis as it is elsewhere. Many analysts bring
      together their clinical observations in a clinical theory that may appear to fit
      their clinical findings well. But a clinical theory is not to be identified with
      a theory of the way the mind works (metapsychology), and an attempt is made, in
      what follows, to clarify the relationship between the two. It is argued that an
      uncritical attachment to clinical theories unsupported by metapsychological
      understanding has been furthered by two main longstanding developments: "object
      relations" theory and the extension of the clinical concept of transference. A
      misapplication of Freud's structural model may, in part, have contributed to
      these developments. This argument, and matters related to it, is pursued in some
      detail in respect to problems of psychoanalytic diagnosis, with special reference
      to some of Anna Freud's contributions to the field that seem to be somewhat
      neglected. Finally, in pointing to metapsychology as a check to clinical
      speculation, some of the illustrations are drawn from psychoanalytic treatment
      material, on the grounds that psychoanalytic work with the patient can be viewed
      in terms of continuing diagnosis.

PMID- 9029958
TI  - Anna Freud: observation and development.
AB  - Anna Freud taught the importance of observation, suggesting that students jot
      down their observations in a systematic manner. She urged observers to amplify
      their notes, which were later discussed in meetings. Observations made in the
      nursery school, for example, were discussed afterwards and classified in a file
      under appropriate headings somewhat similar to the technique used at the Anna
      Freud Centre. In this paper I describe my observations of a subject as an infant
      and a toddler with special reference to the way she looked intensely at the world
      around her. To some degree, the way she herself looked-i.e., her appearance-was
      also interesting. The relationship between the child's looking in infancy and the
      oedipal child's sexual curiosity, exhibitionism, and scoptophilia is suggested by
      these observations.

PMID- 9029959
TI  - The analytic resolution of a developmental imbalance.
AB  - This paper explores the treatment of developmental imbalance in the young child.
      Examples from the treatment of a prelatency girl are examined for the usefulness
      of analysis in redressing early conflicts, which Anna Freud termed "a fertile
      breeding ground for the later infantile neurosis." In this case the child, whose
      history included significant prematurity, also sustained environmental stresses
      to which she reacted by constructing a developmentally precocious independence
      designed to protect her from overwhelming affect states. This defensive stance
      could not be maintained over time, and its breakdown brought her to treatment.

PMID- 9029960
TI  - Developing developmental lines.
AB  - Anna Freud's concept of developmental lines itself followed a complex path of
      development. Ms. Freud came to psychoanalytic maturity during a time when Sigmund
      Freud was rethinking many of his theories. He was engaged in adding to his
      analytic understanding of his patients' past, a new approach to the intrapsychic
      synthesis that takes place in the present and potential future. Anna Freud
      extended this view in her work with children whose treatment and process of
      development overlapped in the continuous present and in the clinically
      foreseeable future. She provided a general system of thinking while respecting
      Freud's distrust of general systems and preserving his commitment to detailed
      observation and to poetic perception. This approach required the ability to
      distinguish clearly among different levels of generalization. Her complex
      experience as both daughter and analysand of her father contributed to her
      intuitive talent in making such distinctions. It was her mourning for her father
      after his death that pulled these trends together into her own unique
      contribution. Her mourning and her contribution took the form of continuing alone
      along the path she and her father had once traveled together. In the concept of
      developmental lines she gave most cogent expression to this continued journey.

PMID- 9029961
TI  - The psychoanalytic legacy of Anna Freud.
AB  - This paper presents some aspects of Anna Freud's work in a way that is rather
      different from the conventional accounts of her contributions. It focuses on some
      of the factors that I believe have led to her particular contribution to
      psychoanalytic theory and practice-inevitably, with special emphasis on her work
      with children. In looking back at Anna Freud's work from today's vantage point,
      it is clear that she was, as Robert Wallerstein put it (1984), a radical
      innovator as well as a staunch conservative.

PMID- 9029962
TI  - Trauma and the developmental process. Excerpts from an analysis of an adopted
      child.
AB  - The adopted child faces a complex developmental task. Having a vital need for a
      parent, he has to deal with the traumatic loss of one set of parents and at the
      same time has to allow new, alien adults to become his parents. Some implications
      of this life situation on the developing representations of self and other and on
      self-other relations are explored in the three-year course of psychoanalysis of a
      five-and-a-half-year-old boy.

PMID- 9029963
TI  - The concept of penis envy revisited. A child analyst listens to adult women.
AB  - Current psychoanalytic scholarship concerning gender development rejects
      recognition of the genital difference, or "penis envy," as central to the
      construction of "femininity," substituting the concept of "primary femininity."
      This shift in the paradigm of gender construction has occurred in part because of
      contributions from child-observational research showing that "gender identity" is
      acquired by age three. It has also been stimulated by the observations of adult
      analysts that interpretations organized around the concept of penis envy appear
      to have little mutative value in contrast to the communications in play and
      action from the analyses of preschool girls, which seem to reflect intense
      intrapsychic conflict stimulated by the girls' recognition of the genital
      difference. Using clinical material, this paper contrasts fantasies of gender
      found in oedipal girls with those presented in the analyses of adult women. The
      differences reflect not only the vicissitudes of gender construction and
      developmental changes in the mind's capacity to adapt to the demands of reality
      but also the fate of aggressive and narcissistic derivatives as they become
      entangled in conflict created by recognition of the inherent limitations of the
      body. The fantasies referred to by the concept "penis envy" are not constitutive
      of femininity; however, they reflect one approach to a defensive solution to
      intrapsychic dilemmas stemming from awareness of bodily and generational limits.

PMID- 9029964
TI  - Oedipal and preoedipal transference transformations. Comments on the analysis of
      a latency-age boy.
AB  - The critical importance of both oedipal and preoedipal unconscious conflicts in
      child and adult analysis as these conflicts unfold through the transference is
      documented using analytic process data. Evidence is provided that demonstrates
      the equal relevance of these psychic conflicts and their continuous interactions.
      The concept of transference transformations is proposed to explain these and
      later psychic conflicts that are resolved through the mutative interpretations
      unique to psychoanalysis. Extensive clinical data from the analysis of a latency
      age boy are presented in support of this thesis. Thus, transference neurosis that
      arises from the infantile neurosis, the structural residue of the Oedipus
      complex, would be subsumed within the group of transference transformations. This
      concept eliminates the obligation to emphasize one developmental phase over
      another.

PMID- 9029965
TI  - The role of passivity in the relationship to the body during adolescence.
AB  - For some adolescents the bodily changes occurring at puberty and during
      adolescence are a source of intense anxiety. Rather than integrate the new sexual
      body within the existing body image, these adolescents respond to the physical
      changes with behavior that attempts to maintain the omnipotent fantasy that they
      are in control of their bodies. Unconsciously they experience the changes as if
      they are able to prevent physical change from taking place and therefore can
      remain passively dependent on their parents. They feel as if the sexual body has
      the power to make them helpless by forcing them to submit passively to its
      demands. The case of an adolescent seen in analysis is presented to illustrate
      the defensive function of such symptomatic behavior and its repetitive,
      compulsive quality.

PMID- 9029966
TI  - Observations on the long-term effects of child analysis. Implications for
      technique.
AB  - This paper examines the issue of the lasting influence of child analysis on
      subsequent development, focusing particularly on the normative developmental
      crisis of the transition from adolescence to adulthood. The cases presented here
      are of two children from a longitudinal study analyzed in childhood with follow
      up to age 35 and the analysis of a young adult whose childhood analysis had been
      reported in the literature. The author considers the significance of changes in
      the theory of technique in child analysis for improving its long-term
      effectiveness.

PMID- 9029967
TI  - The good boy syndrome and malignant academic failure in early adolescence.
AB  - The shift into adolescence coincides with an increase in academic demands that
      reveals a large diagnostic range of difficulties underlying academic
      underachievement or failure at this developmental stage. A group of compliant
      boys of high intelligence and proved abilities, previously apparently well
      adjusted and well-liked, unexpectedly come to attention because of sudden
      academic failure. Their puzzling difficulties indicate a serious underlying
      disorder, including depression, which requires intensive treatment. Intrasystemic
      superego conflicts of ideals form an intrinsic part of the psychic picture.

PMID- 9029968
TI  - Complicating the theory. The application of psychoanalytic concepts and
      understanding to family preservation.
AB  - Anna Freud's recognition of the complex interactions between endowment and
      maturation, innate structuralization and environmental influences, have had a
      profound influence on the development of policies and programs in the United
      States that attempt to improve the adverse conditions, strengthen the tenuous
      maternal ties, and reduce the potential for behavioral problems and intrapsychic
      distress in certain high-risk families. This paper describes and provides a case
      illustration of the application of Ms. Freud's psychoanalytic theories to the
      Yale Family Preservation and Support Programs. It reviews and comments on
      national policies regarding the risks and benefits of family preservation and
      child placement, identifies a paradigmatic shift in the provision of mental
      health care, and cautions against overconfidence in our ability to intervene
      effectively.

PMID- 9029969
TI  - The bereavement process in children of parents with AIDS.
AB  - AIDS has left tens of thousands of children with dead or dying parents. This
      epidemic is forcing us to take a new look at loss in childhood, paying attention
      to the impact of the social and cultural forces in these children's surroundings
      on their internal/psychological worlds. This chapter is a preliminary attempt to
      examine these factors, integrating psychoanalytic concepts, the sociocultural
      context, and treatment issues. Clinical vignettes are used to illustrate
      throughout.

PMID- 9029970
TI  - Oedipal themes in latency. Analysis of the "farmer's daughter" joke.
AB  - A sample of "farmer's daughter" jokes, gathered from archives, personal
      informants, and published collections, is examined in relation to the
      developmental progress of the latency-age boys who most often tell them. The joke
      texts are divided into three categories-oedipal triumph, castration, and
      feminization-each of which represents a different regressive fantasy. Through
      these fantasied scenarios, the joke teller can safely work through some of the
      anxieties he experiences as a result of the recent repression of the oedipal
      conflict. Common themes of latency fantasies such as separation from the family,
      confusion of gender identity, and incestuous desires are all present in the
      texts. Repetition of the farmer's daughter joke not only motivates the child's
      individual psychological progress but also reinforces his or her awareness of
      taboos and socially appropriate behavior. Because the parental injunctions are
      internalized to help consolidate superego formation at the onset of latency and
      the child must now displace incestuous urges with manifestations of conscience,
      the retesting of values through joke telling is important during this
      developmental period.

PMID- 9029971
TI  - Psychological complications of short stature in childhood. Some implications of
      the role of visual comparisons in normal and pathological development.
AB  - This study examines the effect of short stature on the emotional development of a
      subgroup of children who were treated in psychoanalysis and psychotherapy. These
      children became capable of making accurate comparisons of body size in early
      latency as a result of advances in cognitive development. Recognizing their
      comparative smallness left them feeling vulnerable and humiliated. They responded
      with envy and rage toward normally endowed children and vindictively used their
      intellect to outwit and defeat others. They acted as if their suffering exempted
      them from ordinary social rules and expectations. Their preoccupation also
      resulted in arrests in cognitive and social development. Their distrust and
      intention to deceive and defeat posed particular problems for treatment. This
      outcome suggests that visual comparisons of size during early latency are
      implicated in pathological, and therefore in normal, development. Parallels are
      suggested between the subjective experiences of children in this group and the
      experiences of children with other kinds of physical deviations and compromising
      life circumstances.

PMID- 9029972
TI  - Mother's milk. A psychoanalyst looks at breastfeeding.
AB  - This chapter examines the complex experiences and meanings of breastfeeding for
      women engaged in it. My review of the sparse literature to date reveals that
      understanding of breastfeeding has been limited largely to an oral perspective.
      The sociology and physiology of lactation are sketched here to provide a
      background for the multifaceted psychic experiences reported by breastfeeding
      women. Within this more complex context it can be demonstrated that breastfeeding
      kindles aspects of all the psychosexual stages, touching off a cascade of
      fantasies and feelings in the nursing woman. Case vignettes also illustrate the
      broad clinical utility of an interest in breastfeeding. The question arises as to
      why there has been such reticence on the part of both patients and analysts
      regarding breastfeeding. Paying attention to this activity can yield rich and
      useful information about the nursing mother's unconscious attitudes. Issues of
      power, competence, erotism, and aggression are discussed in addition to those of
      orality and nurturance.

PMID- 9029974
TI  - The psychoanalyst of the adolescent.
AB  - The adolescent who comes for psychoanalytic treatment has probably experienced a
      developmental breakdown-a rejection of his or her body and a distorted image of
      himself or herself as being male or female. A critical requisite for work with
      such adolescents is an understanding of one's own adolescent development. The
      internal freedom of the psychoanalyst is an essential ingredient in the treatment
      of the adolescent. This means that the psychoanalyst of the adolescent can
      separate his own sexual life and thoughts from what is lived out in the analytic
      sessions and thus can ensure that the treatment will confront whatever is
      essential and that he will avoid deriving gratification from the treatment
      process through taking over the adolescent's body or feeling that he is secretly
      sharing the intimacies of the patient.

PMID- 9029973
TI  - Psychoanalytic perspectives on adolescent suicide.
AB  - From the beginning of the twentieth century, youthful suicide has posed both a
      clinical and a theoretical challenge for psychoanalysis. This paper examines
      several paradigmatic cases of completed suicide in order to illustrate important
      psychodynamic aspects of adolescent suicide. The contributions of the
      developmental psychoanalytic perspective to our understanding of adolescent self
      destructiveness are discussed, with particular emphasis on Anna Freud's concept
      of developmental lines toward self-care and self-regulation. The applications of
      this developmental psychoanalytic perspective to clinical research on
      vulnerability to adolescent suicide are reviewed.

PMID- 9029975
TI  - Psychoanalysis on the beat. Children, police, and urban trauma.
AB  - Anna Freud's legacy to child psychoanalysis was her understanding and description
      of the complexities of development and her ability to apply her findings to the
      care of children both within and outside of the consulting room. In addition to
      her approach to consultation with nonanalytic professionals concerned with
      children's development and well-being, she established a model for generations of
      child analysts and other analytically oriented clinicians. Both of Ms. Freud's
      concepts of development and collaboration with other professionals have served as
      a basis for the implementation of the Child Development-Community Policing
      Program in New Haven, Connecticut. This collaboration between mental health and
      police professionals will be described in this paper, with particular emphasis on
      the application of Ms. Freud's work to attempts to intervene on the behalf of
      children and families exposed to urban violence.

PMID- 9029976
TI  - States of overstimulation in early childhood.
AB  - This chapter considers states of overstimulation in young children, especially
      those who present with symptomatology consistent with a phenomenologic diagnosis
      of AD/HD (distractible, overactive, and impulsive). These children tend to have a
      history of overstimulation as well as other common developmental factors.
      Characteristic aspects of the deviational ego development of these children are
      described.

PMID- 9029977
TI  - The eternal triangle across cultures. Oedipus, Hsueh, and Ganesa.
AB  - In this chapter we consider the cross-cultural relevance of the Oedipus complex
      by investigating three "oedipal" myths from three disparate cultures: Chinese,
      Indian, and European. Although all three myths concern the same mother-father-son
      triad, they stress different aspects and proscriptions. These are interpreted as
      reflecting the different values that are central to the respective cultures. The
      relationship between these values and child-rearing practices is discussed. We
      conclude that fundamental psychoanalytic concepts are relevant cross-culturally,
      although the content of the Oedipus complex may vary from society to society.

PMID- 9029978
TI  - Lie as narrative truth in abused adopted adolescents.
AB  - Two case examples of abused adopted adolescents are discussed to highlight
      tension within the treatment relationship when the therapist is expected to
      accept without question a clearly unbelievable story. These examples illustrate
      how the lies of such youths can function as narrative truth. The unbelievable
      tales that emerge in the therapeutic work effectively alter the adolescents'
      perceptions about the perplexing loss of continuity, both internal and external,
      that occurred when they were removed from their homes. Characters in the stories
      represent fragmented self- and object-representations as victim, abuser, rescuer,
      and passive onlooker. Counterparts to the patient as victim, abuser, rescuer, and
      passive onlooker can be recognized in the therapist's subjective responses. If
      the therapist can use countertransference to inform an understanding of the
      treatment process, an appreciation emerges that the truth of the lie is in its
      impact. Decisions about how to intervene can then be crafted. The second
      separation-individuation intrinsic to adolescent development is understood to
      provide a ripe opportunity for this working-through process.

PMID- 9029979
TI  - What's in name? Psychiatric epidemiology and social psychiatry at the turn of the
      century.

PMID- 9029980
TI  - In what ways do characteristics of psychiatric services determine contact rates
      and use of services? The Nordic Comparative Study on Sectorized Psychiatry.

PMID- 9029981
TI  - The genetic epidemiology of psychiatric disorders: a current perspective.
AB  - Psychiatric genetic epidemiology has, as a field, undergone considerable change
      in the last two decades. My goal here is to provide a brief, selective and
      inevitably personal overview of where the field has come from, where it is now
      and where it might be going. Methodologic issues will be emphasized, particularly
      those of an "epidemiologic" nature. I will organize this review around three of
      the major methods used in psychiatric genetics: family studies, twin studies and
      linkage studies.

PMID- 9029982
TI  - The Nordic Comparative Study on Sectorized Psychiatry. Part V. Contact rates,
      contact patterns and care level at index contact.
AB  - As part of a Nordic comparative study on sectorized psychiatry in seven Nordic
      catchment areas, a prospective investigation of contact rates of new patients and
      pathways to the psychiatric services was performed. The results showed that there
      was more than a twofold difference between the services in the total contact
      rates. Regarding diagnostic groups, contact rates for neurosis were predominant
      in three of the services, while adjustment disorders, dependencies and
      personality disorders were predominant in other the services. The contact rate of
      functional psychosis, as well as the ratio of psychotic patients to the total
      contact rate were highest in two catchment areas serving inner parts of big
      cities. The most common way of getting into contact with the services was by self
      referral, 39.4% of total referrals, followed by primary care referrals, although
      there were large differences between the services. Psychotic patients made
      contact with the services to a significantly less extent by self-referral. The
      majority of patients were treated in outpatient care at entry to the services,
      with a large variation between the services. It was also found that inpatient
      care at index contact was predicted by clinical characteristics-a diagnosis of
      psychosis and a history of former inpatient care-as well as by social
      characteristics-male, widowed or divorced, sick pension/old age pension.

PMID- 9029983
TI  - Counting the uncatchable? An epidemiological method for counting drug misusers.
AB  - Service provision and treatment outcome for problem drug users are receiving
      increased attention, although both are hindered by the lack of good
      epidemiological data. A technique of population enumeration called capture
      recapture methodology (CRM) is currently being advocated for use in populations
      that are otherwise hard to count. CRM is explained and some of its limitations
      discussed. Studies that have used this methodology are examined.

PMID- 9029984
TI  - Epidemiology of somatoform disorders: a community survey in Florence.
AB  - Since the exclusion of somatic causes is necessary for somatoform disorders (SMD)
      to be diagnosed, there is little information on the prevalence of such disorders
      in the community. As the method we have previously developed [general
      practitioners (GPs) with psychiatric training who interview samples
      representative of the general population] seemed to be appropriate to deal with
      the problem, we carried out a community survey focused on somatoform disorders.
      The prevalence rates of DSM-III-R somatoform disorders were studied in two wards
      of the city of Florence. In order to be representative of the general population,
      673 subjects randomly selected were interviewed by their own GP. Four GPs, all
      with specific training in psychiatry, participated in the interviewing process.
      The 1-year prevalence figures were as follows: 0.7% body dysmorphic disorder;
      4.5% hypochondriasis; 0.6% somatoform pain disorder; 0.3% conversion disorder;
      0.7% somatization disorder; 13.8% undifferentiated somatoform disorder. No
      specific comorbidity was found between somatoform disorders and mood or anxiety
      disorders. Although the sample investigated was small, this study may be seen as
      one of the first in an area where knowledge is still scant. The prevalence rates
      of somatoform disorders were generally found to be slightly lower than expected.

PMID- 9029986
TI  - Quality of life as an outcome measure in evaluating mental health services: a
      review of the empirical evidence.
AB  - This paper addresses the question of how well quality of life measures function
      as valid and sensitive outcome indicators of mental health services. Findings
      from the major empirical studies of quality of life in the mental health area
      over the last 15 years are reviewed. The extent to which existing studies provide
      evidence of the ability of quality of life measures to discriminate the impact of
      service interventions on the well-being of psychiatric clients is examined.
      Findings from cross-sectional, comparative, repeated-measures and randomised
      studies are presented. The available empirical evidence is critically examined
      and the methodological and theoretical implications of current findings for
      future work are considered.

PMID- 9029987
TI  - Upstream like a salmon (early diagnosis of hemochromatosis)

PMID- 9029985
TI  - Early onset depression: the relevance of anxiety.
AB  - The aim of this study was to determine risk factors that may differentiate early
      onset from late onset depression. A non-clinical cohort that had been assessed
      from 1978 to 1993 at 5 yearly intervals and that had a high prevalence rate of
      lifetime depression took part in the study. We established an appropriate age cut
      off to distinguish early onset (i.e. before 26 years) of major and of minor
      depression, and examined the relevance of a number of possible determinants of
      early onset depression assessed over the life of the study. Despite several
      dimensional measures of depression, self-esteem and personality being considered,
      they generally failed (when assessed early in the study) to discriminate
      subsequent early onset depression, with the exception of low masculinity scores
      being a weak predictor of major and/or minor depression. Early onset depression
      was strongly predicted, however, by a lifetime episode of a major anxiety
      disorder, with generalised anxiety being a somewhat stronger and more consistent
      predictor than panic disorder, agoraphobia and minor anxiety disorders (ie social
      phobia, simple phobia). The possibility that anxiety may act as a key
      predispositional factor to early onset depression and to a greater number of
      depressive episodes is important in that clinical assessment and treatment of any
      existing anxiety disorder may be a more efficient and useful strategy than
      focussing primarily on the depressive disorder.

PMID- 9029988
TI  - State of South Dakota's child: 1996.
AB  - The trend of decreasing annual births in South Dakota continued with a decline to
      10,470 live births in 1995. The state's infant mortality rate (IMR) of 9.5 per
      1,000 live births for 1995 decreased from 9.6 in 1994, but has essentially varied
      little over the past nine years and is currently higher than the nation's rate of
      7.5. Neonatal mortality (zero to 27 days of life) in South Dakota decreased to
      5.2 in 1995 from 5.5 in 1994 with the decline attributable to fewer deaths of
      newborns of color. Nonetheless, similar to 1994 this rate is higher than the
      provisional national 1995 rate of 4.8. Post neonatal mortality in the state
      increased in 1995 among both whites and infants of color. An examination of
      causes of infant deaths in South Dakota shows that the state's rates of infant
      deaths due to congenital anomalies and Sudden Infant Death Syndrome (SIDS) exceed
      those noted nationally. The US Public Health Service's "Back to Sleep" campaign,
      initiated in 1994, is described as a contributor to the recent declining national
      rate of SIDS and its acceptance is urged as a preventive measure to decrease
      tragic loss of new life in South Dakota.

PMID- 9029989
TI  - Beta-blockade in heart failure: a potential role.

PMID- 9029992
TI  - Physician-assisted suicide. Above all else do no harm.

PMID- 9029990
TI  - No alternative.

PMID- 9029993
TI  - Employers continue to embrace managed care.

PMID- 9029994
TI  - Ask TMA....

PMID- 9029995
TI  - Loss prevention case of the month. Lost in the shuffle of a busy practice?

PMID- 9029996
TI  - Boerhaave's syndrome--an elusive diagnosis.

PMID- 9029997
TI  - Excessive sweating: unusual side effect of megestrol acetate therapy.

PMID- 9029998
TI  - FDA requires manufacturers to fortify grain products with folic acid.

PMID- 9030001
TI  - The disappearance of the general internist.

PMID- 9029999
TI  - Intra-arterial thrombolysis in acute ischemic stroke.

PMID- 9030002
TI  - Duties to science, duties to God: medical theory, physiology, and the discourse
      on morality in nineteenth-century America.

PMID- 9030003
TI  - Factory work for doctors: the early years of the Section on Industrial Medicine
      and Public Health of the College of Physicians of Philadelphia.

PMID- 9030004
TI  - The Hyrtl skull collection.

PMID- 9030005
TI  - Dr. Ames defines his profession.

PMID- 9030006
TI  - Naval medicine in Philadelphia, 1815-1840.

PMID- 9030007
TI  - Doctors of the old school: Philadelphia physicians of the middle period (from
      Benjamin Rush to S. Weir Mitchell).

PMID- 9030008
TI  - Prazosin: scorpion envenoming and the cardiovascular system.

PMID- 9030009
TI  - Chloroquine retinopathy.

PMID- 9030010
TI  - Scorpion envenoming and the cardiovascular system.

PMID- 9030011
TI  - Eye damage from chloroquine as an antimalarial: misuse makes safe medicines
      unsafe.

PMID- 9030013
TI  - Conducting a descriptive survey: 2. Choosing a sampling strategy.

PMID- 9030012
TI  - Surgical ascariasis in children in Kashmir.
AB  - A retrospective study of 85 children aged 3-12 years revealed 25 cases who needed
      surgical intervention due to ascariasis. The surgical conditions found at
      laparotomy were intestinal obstruction (18) appendicitis (3), ileal perforation
      (2), biliary ascariasis (2). The study highlights the high incidence of surgical
      ascariasis among children with abdominal complaints in an endemic area.

PMID- 9030014
TI  - Non-specialist management of tropical talipes.
AB  - Talipes equinovarus (clubfoot) is a complex deformity which in the West is
      usually treated by trained orthopaedic surgeons. In developing countries,
      however, most clubfeet will need to be treated by medical officers lacking
      specialist training. We report one author's experience in treating clubfeet in a
      small, rural East African hospital and review the literature in order to assist
      other non-specialists in managing this difficult condition in the face of poverty
      and poor parental compliance.

PMID- 9030015
TI  - Observed versus expected obstetric complications: an assessment of coverage of
      obstetric care in developing countries.
AB  - The objective of this study was to evaluate access to obstetric care in a rural
      district in East Africa using easily collected and evaluated data and avoiding
      expensive field surveys, complicated study design or statistical methods. The
      number of observed obstetric complications occurring during 12 months in a rural
      East African district hospital (the only institution with surgical facilities and
      access to blood transfusion in the district) were compared to the number of
      expected complications the district should 'generate'. Of the expected > 10000
      deliveries < 25% took place in the district hospital. The place of confinement
      for the other deliveries was not determined. As compared to the total number of
      expected conditions within the study district < 25% of the breech and < 45% twin
      deliveries took part in the district hospital and < 10% of pregnancies
      complicated by placental abruptions and < 5% of the pregnancies complicated by
      placenta praevia were managed in the district hospital. Comparing the number of
      serious pregnancy complications which were managed in the hospital to the total
      expected number for a particular region allows a simple assessment of the
      accessibility of obstetric care. This ratio might be more useful when evaluating
      obstetric care than traditional parameters as it stresses the importance of
      accessibility of care for the whole community.

PMID- 9030016
TI  - Basic care reduces neonatal hyperbilirubinaemia.
AB  - We studied the frequency of jaundice, bilirubin estimations, phototherapy
      administration and exchange transfusions performed at 5 year intervals (1981,
      1986 and 1991) among babies admitted to special care unit and those managed in
      postnatal ward, showing a decline which was significant except for the number of
      exchange transfusions performed. The number of term babies with serum bilirubin >
      15 mg/dl and preterm babies with serum bilirubin > 10 mg/dl also declined
      significantly without prophylactic phototherapy or pharmacotherapy.

PMID- 9030018
TI  - Why wait so long for child care? An analysis of waits, queues and work in a South
      African urban health centre.
AB  - Long waits at large urban clinics obstruct primary care delivery, imposing time
      costs on patients, deterring appropriate utilization and causing patient
      dissatisfaction. This paper reports on an innovative attempt by staff in a large
      South African urban health centre to analyse a system of queues and preventive
      and curative services for pre-school children, and thereafter to evaluate
      changes. The study had a cross-sectional work study design, with repeated
      measurement of waiting times after 13 months. At baseline the preventive clinic
      was found to have several inessential processes and waits; these were eliminated
      or overlapped, and clinic sessions per week were increased. A year later median
      waiting times had decreased substantially in the preventive clinic, but had
      increased in the curative clinic. Simple research can explain long waits, inform
      and measure changes, and provide evidence to justify primary care integration and
      would be useful in health centres and hospital outpatient departments in
      developing countries.

PMID- 9030017
TI  - Emergency endoscopy in patients with portal hypertension having upper
      gastrointestinal bleeding.
AB  - During the last 4 years, 147 patients suffering from portal hypertension with
      acute upper gastrointestinal bleeding were subjected to emergency endoscopy soon
      after they were resuscitated. Seventeen (11.5%) patients were referred to us with
      a clinical diagnosis other than portal hypertension. The causes of bleeding as
      seen during endoscopy were: oesophageal varices (n = 130; 88%), gastric varices
      (n = 11), gastric ulcer (n = 2) portal hypertensive gastropathy (n = 2) and
      erosive gastritis and duodenal ulcer in one patient each. All patient bleeding
      from oesophageal varices except one underwent emergency endoscopic sclerotherapy.
      One hundred and twenty-one (94%) stopped bleeding immediately. Rebleeding was
      seen in 11% and was effectively controlled by a second session of sclerotherapy
      in all but one patient. Twenty (14%) patients died. It is concluded that
      emergency endoscopy has a definite role in the management of patients with portal
      hypertension complicated by gastrointestinal bleeding.

PMID- 9030019
TI  - Diagnosis of HIV infection.
AB  - AIDS is the clinical manifestation of cellular immunodeficiency caused by HIV
      infection. A characteristic feature of HIV-infection is the lifelong coexistence
      of HIV and antibodies against it in the blood. The routine diagnosis of HIV
      positivity is based mainly on HIV-antibody screening by ELISA and confirmation by
      Western blotting. Improvements in diagnostic sensitivity are expected from the
      introduction of HIV-genome detection by polymerase chain reaction technique.

PMID- 9030020
TI  - Chronic volvulus of the stomach: to operate?
AB  - Chronic volvulus of the stomach is a relatively rare entity. We present a series
      of six cases diagnosed over the past 18 months. Three patients underwent surgical
      treatment by gastropexy alone or with gastrojejunostomy while the other three
      were managed conservatively. Symptomatic relief was equally good in both groups,
      in the short term.

PMID- 9030021
TI  - A teaching hospital-based drug information service in Nepal.

PMID- 9030023
TI  - Ureteral reconstruction using the vermiform appendix flap in a patient with a
      post traumatic uretero cutaneous fistula.

PMID- 9030022
TI  - Prevalence of hepatitis B surface antigen and HCV antibodies in hepatocellular
      carcinoma cases in Karachi, Pakistan.
AB  - Hepatocellular carcinoma (HCC) is a common cancer the world over. In Pakistan it
      has an incidence of 8/ 100,000 per annum. To assess the prevalence of Hepatitis B
      virus (HBV) and Hepatitis C virus (HCV) infections in biopsy proven cases of HCC
      a serological study was conducted at Screening Laboratory of Blood Transfusion
      Services, Jinnah Postgraduate Medical Centre. Of 54 sera of HCC tested for HBV
      and HCV infections, 67% showed HBV infection, and 33% HCV infection. Among them
      24% were positive for both HBV and HCV infections. No HBV and HCV infection was
      found in 24% cases of HCC. Our findings suggest viral association for most of the
      HCC cases reported in the country. We suggest an immediate intervention strategy
      to prevent the spread of HBV and HCV infections by mandatory screening of blood
      for HBV and HCV infections, and the use of disposable/sterilized needles,
      instruments for all invasive procedures. For the prevention of vertical
      transmission of HBV infections all pregnant women should be screened and
      vaccinated and HBV vaccination should also be included in EPI (expanded programme
      for immunization).

PMID- 9030025
TI  - A 3-year-old boy with tuberculous epididymo-orchitis.
AB  - The authors report the case of a 3-year-old child with tuberculous epididymo
      orchitis. The only presenting symptom was testicular, epididymis and scrotal
      swelling and pain. Diagnosis was reached after histopathological examination of
      epididymis and testis tissues. The response to antitubercular drugs given with
      prednisolone was rapid. This case emphasizes the importance of considering
      tuberculosis in differential diagnosis of testicular and epididymal enlargement
      in young children in an endemic area despite the absence of systemic, pulmonary
      and urinary manifestations.

PMID- 9030024
TI  - Management of oesophageal foreign bodies in a rural hospital in developing
      countries.

PMID- 9030027
TI  - Rapunzel syndrome.

PMID- 9030026
TI  - Recurrent pyogenic cholangitis: 'sump syndrome' following choledochoduodenostomy.
AB  - An uncommon and late complication of side-to-side choledochoduodenostomy (CDD),
      the 'sump syndrome', developed in a patient 4 years after surgery. Recurrent
      right upper abdominal pain, fever with chills and rigors and latterly, mild
      jaundice made her seek repeated hospital admissions which were treated
      successfully with antibiotics. During the last admission, ultrasonography,
      endoscopic retrograde cholangiography (ERC), computerized scanning (CT) and
      hepatic iminodiacetic acid (HIDA) scan using Tc99m confirmed multiple
      intrahepatic calculi with proximal dilatation, debris in the distal blind segment
      and delayed excretion through the CDD. At surgery, the choledochoduodenostomy was
      taken down and a Rouxen-Y hepaticojejunostomy (RHJ) was fashioned after ductal
      clearance. The closed end of the Roux loop was placed subcutaneously for
      subsequent percutaneous access for cholangiography and removal of calculi. She is
      asymptomatic and well 28 months after surgery.

PMID- 9030028
TI  - Ultrasound diagnosis of subdural abscess complicating meningitis.

PMID- 9030029
TI  - Presentation of parasites and the radiology of parasitic diseases.

PMID- 9030030
TI  - Mycobacterium ulcerans skin infection in a patient with HIV infection: is this
      incidental?

PMID- 9030031
TI  - Conduction defect following pentavalent antimony therapy in visceral
      leishmaniasis.

PMID- 9030032
TI  - Factors associated with the utilization of trained traditional birth attendants
      in rural Bangladesh.

PMID- 9030033
TI  - Improvisation of a T-tube.

PMID- 9030034
TI  - The Gonococcal Antimicrobial Surveillance Programme (GASP). WHO western Pacific
      region, 1995.

PMID- 9030035
TI  - Education about research.

PMID- 9030036
TI  - Perceived control and well-being in Parkinson's disease.
AB  - Sense of control in the context of an uncontrollable chronic illness is explored
      by analyzing the impact of the patient's perceived control over symptoms (PCS)
      and perceived control over disease progression (PCDP) on patient and caregiver
      outcomes. PCS was significantly associated with patient well-being, caregiver
      well-being, and less caregiver burden. No relationship was found between PCDP and
      patient well-being, caregiver well-being, or caregiver burden. Findings support
      the importance of symptom management, viewing the patient-caregiver dyad as a
      unit, and the need for future research on control and transition points in
      chronic illness.

PMID- 9030037
TI  - Disordered eating behaviors and bone-mineral density in women who misuse alcohol.
AB  - Because lower bone-mineral density is one potential physiological consequence of
      eating disorders and chronic alcohol misuse, the risk for osteoporosis may be
      compounded in women who have both conditions. This study investigated the
      frequency of eating disorders in 25 women who misuse alcohol and compared bone
      mineral density between those with and without multiple disordered eating
      behaviors. Disordered eating behaviors were assessed through the EAT-26 (Eating
      Attitudes Test) and a structured interview addressing binge eating, purging, and
      other weight-control behaviors. Bone-mineral density was measured using dual
      energy x-ray densitometry. Although only one woman met the DSM-III-R criteria for
      a current eating disorder, 12% had past histories suggestive of anorexia nervosa
      and 40% had multiple disordered eating behaviors with bulimic features. Bone
      mineral density of the femoral neck was 9.3% greater in women with multiple
      disordered eating behaviors (p < or = .05).

PMID- 9030038
TI  - Decisions to have a baby by HIV-infected women.
AB  - As the epidemiologic picture of HIV changes to include increased numbers of women
      of childbearing age, particularly those of African American heritage and those
      from rural southern cultures, those who provide services to these women need to
      understand the processes used by HIV-infected women to make reproductive
      decisions. Focus-group data with subsequent content analysis were used to
      discover themes surrounding pregnancy decisions among 22 women in two
      predominantly rural southeastern states. The results both validated and amplified
      previous findings and added new perspectives. The analyses revealed six
      overarching themes: spiritual and religious beliefs, knowledge and beliefs about
      HIV, previous experience with childbearing attitudes of families and sex
      partners, personal health, and intrapersonal motivation to have a baby.

PMID- 9030039
TI  - Benefits and burdens of genetic carrier identification.
AB  - This qualitative study examined experiences of adults requesting genetic-carrier
      testing for four autosomal-recessive and X-linked-recessive disorders. The sample
      consisted of 34 adults with a positive family history or membership in an ethnic
      group at risk for the inherited disorder. A semistructured interview guide was
      used to collect data during an interview 1 month after receipt of test results.
      Noncarriers experienced benefits of emotional relief and freedom to move ahead
      with reproductive planning. Carriers experienced burdens of sadness and loss of
      reproductive expectations. Some subjects in both groups experienced difficulty
      disclosing results to selected family members and expressed concerns regarding
      disclosure of testing to insurance providers.

PMID- 9030040
TI  - Home-care nurses as strangers in the family.
AB  - As nurses move from the hospital into the home setting, they are challenged to
      examine boundaries of practice and family-nurse relationships. This
      phenomenological study was undertaken to explore the experiences of nurses
      working with families of technology-dependent children in the home. The main
      theme emerging from the data was the nurse's presence as "a stranger in the
      family." Additional themes focused on the nurse's advocacy for the child and
      family, boundary setting, collaboration, and occupational demands.

PMID- 9030041
TI  - Nurses' experience with implementing developmental care in NICUs.
AB  - The aim of this study was to gain insight into nurses' (N = 8) experience of
      working in a neonatal intensive-care unit (NICU) that incorporated the
      developmental-care approach. Although Als's model is family centered, the basic
      social process identified by nurses was putting the baby first. The process of
      putting the baby first was uncovered using grounded-theory methodology. The
      process included three phases: learning, reacting, and advocating/nonadvocating.
      In each of the phases, four main concepts--encountering, appraising, supporting,
      and gaining sensitivity--emerged from the data. Nurses appraised the advantages
      and disadvantages of this therapeutic approach not only to the infant but also to
      themselves.

PMID- 9030042
TI  - Afghan refugee issues in the U.S. social environment.
AB  - Since Afghan refugees began coming to the United States in the early 1980s, the
      Afghan community of the San Francisco Bay Area has become the largest in the
      United States. This population copes with a number of stressors that negatively
      affect their health and psychological well-being. Based on an ethnographic study,
      we focus on the social context in which Afghan refugees find themselves,
      describing Afghans' perceptions of their interactions with mainstream American
      citizens and health and social service providers. The theme running through all
      such interactions is information--its scarcity, character, and cultural
      differences in type, purposes, and means of transmission. Quotes from interviews
      illustrate four types of problems: economic and occupational problems, health
      care access, family and children's issues, and immigration issues/ethnic bias.
      Policy and program recommendations are applicable to other recent refugee
      populations that experience similar information problems with regard to the
      dominant society.

PMID- 9030043
TI  - Nurses' roles in protecting human subjects.
AB  - This article highlighted several nursing roles and strategies for the protection
      of human subjects including the importance of socializing new nurses into their
      role responsibilities and reporting questionable scientific conduct. Although
      different strategies were suggested in relation to each role, one commonality
      pervaded--nurses, by virtue of their license and focus of their professional
      discipline, are keys to the protection of human subjects in research.

PMID- 9030044
TI  - Triplet births: trends and outcomes, 1971-94.
AB  - OBJECTIVES: This report describes changes in the number and ratio of live births
      in triplet and other higher order multiple deliveries from 1971 to 1994 by
      maternal race, age, education, and marital status. The report also examines the
      birth outcomes of triplets compared with singletons, including overall gestation
      specific, and birthweight specific infant mortality rates. METHODS: Birth data
      are obtained from the U.S. certificates of live birth. Mortality data were
      obtained from the Linked Birth and Infant Death Data Sets for the 1983-91 birth
      cohorts. Most analyses are based on triplet and other higher-order multiple
      births (quadruplet and quintuplet and greater births) in the aggregate. (Triplet
      births comprise about 92 percent of all higher order multiple births.) Triplet
      and other higher order birth ratios for most variables are computed by combining
      data for years 1982-84 and 1992-94, and for infant mortality by combining birth
      cohorts for years 1987-91. FINDINGS: Between 1971 and 1994 the number and ratio
      of triplet births quadrupled, rising from 1,034 to 4,594, and from 29.1 to 116.2
      per 100,000 live births. Most of the increase was among births to white mothers,
      particularly among married and more educated mothers. Only about one-third of the
      increase in triplet birthing among white mothers between 1989 and 1994 could be
      attributed to changes in the maternal age distribution. Massachusetts reported
      the highest triplet birth ratio (215.9), more than twice the U.S. ratio (105.5).
      Other States with comparatively high ratios were New Hampshire, New Jersey, and
      Iowa. Nine of 10 triplets were born preterm compared with 1 of 10 singletons. The
      average triplet weighed 1,698 grams at birth, one-half that of the average
      singleton (3,358 grams). Triplets were about 12 times more likely to die during
      the first year of life as singletons, but had a survival advantage over
      singletons at lower gestations and birthweights.

PMID- 9030045
TI  - Supercritical fluid extraction of 11C-labeled metabolites in tissue using
      supercritical ammonia.
AB  - Supercritical fluid extraction (SFE) of 11C-labeled tracer compounds and their
      metabolites from biological tissue was performed using supercritical ammonia in
      an attempt to develop a rapid extraction procedure that allowed subsequent
      analysis of the labeled metabolites. Metabolites were extracted from kidneys and
      brain in rats given in vivo injections of the radiotracers O-[2-11C]acetyl-L
      carnitine and N-[11C]methylpiperidyl benzilate, respectively. Only a minimal
      sample pretreatment of the tissue was necessary, i.e., cutting into 10-20 pieces
      and mixing with the drying agent Hydromatrix, before it was loaded into the
      extraction vessel. Extraction efficiency was measured for SFE at temperatures
      over the range of 70-150 degrees C and a pressure of 400 bar. For O-[2-11C]acetyl
      L-carnitine, 66% of the radioactivity was trapped in the collected fractions and
      12% remained in the extraction vessel. For the more lipophilic N
      [11C]methylpiperidyl benzilate, 93% of the activity was collected and less than
      1% remained in the extraction vessel. Labeled metabolites were analyzed by LC and
      also, in the case, of O-[2-11C]acetyl-L-carnitine by LC/MS. The complete
      extraction procedure, from removal of the biological tissue until an extract was
      ready for analysis, was 25 min, corresponding to about one half-life of the
      radionuclide 11C.

PMID- 9030046
TI  - Counting basic sites in oligopeptides via gas-phase ion chemistry.
AB  - Cations derived from oligopeptides ranging from laminin fragment (5 residues) to
      beta-lactoglobulin (162 residues) have been subjected to gas-phase ion/molecule
      reactions with hydroiodic acid. The sum of the ion charge state and the maximum
      number of molecules of hydroiodic acid that attach to the ion is equal to the
      total number of lysines, arginines, histidines, and N-termini consisting of a
      primary amine for ions derived from all 21 oligopeptides studied. These results
      suggest that ion/molecule reactions can provide useful information regarding
      oligopeptide basic site number, which might be used as a criterion for searching
      protein data bases instead of, or in conjunction with, use of proteolytic
      digestion or gas-phase ion dissociation procedures.

PMID- 9030047
TI  - Detection of modified peptides in enzymatic digests by capillary liquid
      chromatography/electrospray mass spectrometry and a programmable skimmer CID
      acquisition routine.
AB  - A method for the identification of multiple covalent protein modifications in
      enzymatic protein digests by specific marker ion signals in a single analysis is
      described. This method is based on the combined strengths of capillary liquid
      chromatography (microLC) to purify, concentrate, and resolve complex mixtures and
      electrospray mass spectrometry (ESI-MS) to selectively and sensitively detect
      ions. A variety of modification-specific marker ions can be generated using a
      programmable skimmer collision-induced dissociation (sCID) acquisition routine,
      which allows for flexibility in the (i) number of marker ions monitored under
      single-ion monitoring conditions, (ii) selection of optimal polarity for both
      marker ions and molecular ions, (iii) use of variable dwell times for marker
      ions, and (iv) selection of optimal sCID offset. Using this combined method of
      microLC/ESI/sCID-MS, phosphorylated, sulfated, acrylamide-modified, and
      glycosylated peptides were identified in a model enzymatic digest at 200 fmol.
      The capability of reversed-phase LC to resolve isomeric compounds which cannot be
      identified by low-energy CID underscores the utility of this combined method.
      Further capabilities of this technique are demonstrated by the analysis of
      biologically important proteins.

PMID- 9030048
TI  - On-line HPLC electrospray mass spectrometry of phosphorothioate oligonucleotide
      metabolites.
AB  - Metabolism of 2'-deoxyphosphorothioate oligonucleotides ISIS 11061 and ISIS 11637
      was examined with capillary gel electrophoresis (CGE) and on-line HPLC
      electrospray mass spectrometry (HPLC/ES-MS). Oligonucleotides were isolated from
      plasma, liver, and kidneys of rats injected with ISIS 11061 and ISIS 11637.
      Metabolites found in plasma were consistent with 3'-exonuclease activity.
      Metabolites isolated from liver and kidney were consistent with 3'- and/or 5'
      exonuclease activity. HPLC/ES-MS analysis of ISIS 11061 isolated from kidney
      indicated extensive degradation from the 3' terminus, but metabolites consistent
      with 5' degradation and combinations of 3' and 5' truncations also were observed.
      ISIS 11061 isolated from liver showed less extensive degradation. The 5'
      truncated metabolites represented the predominant species in contrast to the
      kidney sample. Metabolites with masses consistent with combinations of 3' and 5'
      truncations were also observed in liver. The metabolic profiles generated by CGE
      analysis of these samples agreed qualitatively with mass spectrometric results.
      HPLC/ES-MS enabled the simultaneous determination of degradation products that
      are the same length but differ in composition. CGE could discriminate species
      that differed by one nucleotide in length. HPLC/ES-MS was shown to be a useful
      tool to study the complex metabolism of antisense oligonucleotides in vivo.

PMID- 9030049
TI  - Open-tubular capillary electrochromatography with an on-line ion trap
      storage/reflectron time-of-flight mass detector for ultrafast peptide mixture
      analysis.
AB  - In this work, a novel open-tubular column (OTC) capillary electrochromatography
      (CEC) system has been coupled to an on-line ion trap storage/reflectron time-of
      flight mass spectrometer for ultrafast peptide mixture analysis. Reversed-phase
      OTCs prepared by the sol-gel process were coated with an amine, which greatly
      enhanced the electroosmotic flow in an acidic buffer solution and considerably
      reduced nonspecific adsorption between the peptides and the column wall. A six
      peptide mixture could be separated to baseline within 3 min on this system. A
      full mass range detection speed of 8 Hz was used in all these experiments, which
      was sufficiently rapid to maintain the high efficiency of ultrafast separations.
      Because of the high duty cycle of the mass spectrometer and the column path
      length-independent concentration-sensitive feature of the electrospray ionization
      process, high-quality total ion chromatograms could be obtained with injections
      of only 1-2 fmol of peptide samples. A concentration limit of detection of 1 x
      10(-6) M was also achieved due to the preconcentration capability of CEC. In
      addition, a novel gradient CEC device was demonstrated which did not result in a
      pressure-driven flow. A tryptic digest of horse heart myoglobin was successfully
      separated on the gradient CEC system within 6 min. The use of the mass
      spectrometer increased the resolving power of this system by clearly identifying
      coeluting components.

PMID- 9030050
TI  - A new strategy for MALDI on magnetic sector mass spectrometers with point
      detectors.
AB  - We have developed a new strategy to perform matrix-assisted laser
      desorption/ionization (MALDI) on magnetic sector instruments equipped with
      nonintegrating point detectors. This approach is based on using liquid matrices
      to provide very long-lasting analyte ion currents and to overcome the inability
      of these instruments to simultaneously detect ions over a range of mass-to-charge
      values. Here, we demonstrate some of the capabilities of MALDI on a magnetic
      sector for analyzing biological samples. These capabilities include the ability
      to perform MS/MS experiments, to attain resolutions over 8000 (full width at half
      maximum), and to determine relative molecular masses with < 20 ppm error for a
      single measurement and < 2 ppm error for the average of five measurements. All
      three of these experiments can be performed on the same 10 pmol sample loading.
      We also compare the results of MALDI on a magnetic sector instrument with point
      detection with the reported capabilities of MALDI on time-of-flight-based mass
      analyzers and with fast atom bombardment on sector-based instruments. This work
      demonstrates that researchers with magnetic sector-based instruments can perform
      MALDI experiments with a relatively simple and inexpensive upgrade to their
      existing equipment.

PMID- 9030051
TI  - pH-dependent isoform transitions of a monoclonal antibody monitored by micellar
      electrokinetic capillary chromatography.
AB  - Within the pH range 2-12, the monoclonal chimeric antibody BR96 can be separated
      into one to five isoforms by micellar electrokinetic capillary chromatography
      (MECC). The distribution of the immunoglobulin between these isoforms is pH
      dependent and apparently reversible. Some of the changes in the electrophoretic
      profile are represented by alterations in the immunoglobulin secondary structure.
      MECC and CD data demonstrate that, in other cases, differences in electrophoretic
      mobilities of the intact and acid-stressed antibody molecules were not due to
      differences in the ionization of the protein functional groups or changes in
      secondary structure, but rather resulted from differences in the exposure of the
      molecule's structural elements to the solvent. The results indicate that the
      interaction of the isoforms with sodium dodecyl sulfate micelles plays a crucial
      role in MECC isoform separations. The formation of analyte-micelle complexes was
      postulated to make electrophoretic mobilities, especially of large protein
      molecules, susceptible to subtle conformational changes that are not detectable
      by other methods.

PMID- 9030052
TI  - Microchip-based capillary electrophoresis for immunoassays: analysis of
      monoclonal antibodies and theophylline.
AB  - A microchip capillary electrophoresis device has been used to separate the
      reaction products of homogeneous, immunological reactions within approximately 40
      s. Determination of monoclonal mouse IgG in mouse ascites fluid, via a direct
      assay, and the drug theophylline in serum samples, via a competitive assay, was
      demonstrated on-chip. The mouse anti-bovine serum albumin IgG assay gave a linear
      calibration curve up to at least 135 micrograms/mL, with +/- 3% precision. The
      theophylline assay gave a threshold for detection of 1.25 ng/mL in diluted serum.
      A calibration curve of signal vs undiluted log[theophylline] is linear from 2.5
      to 40 micrograms/mL, which includes the therapeutically useful range.
      Theophylline recoveries in spiked samples were 100%, within an experimental error
      of +/- 5%. A buffer system consisting of 0.05 M tricine adjusted to pH 8.0, 0.01%
      (w/v) Tween 20, and approximately 40 mM NaCl was used. This buffer allowed for
      adequate separation (40,000 plates for theophylline; 1000 plates for theophylline
      antibody complex and for human IgG) and gave reproducibility of migration times
      of 1-1.5% over 4-day periods, indicating minimal problems from adsorption in the
      uncoated chips.

PMID- 9030053
TI  - Capillary electrochromatography and capillary electrochromatography-mass
      spectrometry for the analysis of DNA adduct mixtures.
AB  - Capillary electrochromatography (CEC) is an emerging technique that can be
      applied to the separation of neutral compound mixtures and provides a versatile
      alternative to micellar electrokinetic chromatography. In this paper, CEC is
      applied to the separation of polycyclic aromatic hydrocarbons (PAHs) and in vitro
      reaction products of PAH deoxynucleoside adducts. Some unique features related to
      CEC, such as convenience of stopping the flow, nanoliter flow rate, and low
      sample consumption, are discussed. On-column focusing in CEC can be conducted by
      introducing the analytes in a solution of lower solvent strength followed by
      elution with a stronger mobile phase, in a manner analogous to that used in
      normal HPLC (e.g., a 10-fold preconcentration factor can be readily achieved).
      Coupling of CEC to mass spectrometry for the detection of a relatively dilute DNA
      adduct mixture solution (10(-6) M) using the on-column focusing method is also
      presented.

PMID- 9030055
TI  - Multichannel microchip electrospray mass spectrometry.
AB  - Microfabricated multiple-channel glass chips were successfully interfaced to an
      electrospray ionization mass spectrometer (ESI-MS). The microchip device was
      fabricated by standard photolithographic, wet chemical etching, and thermal
      bonding procedures. A high voltage was applied individually from each buffer
      reservoir for spraying sample sequentially from each channel. With the sampling
      orifice of the MS grounded, it was found that a liquid flow of 100-200 nL/min was
      necessary to maintain a stable electrospray. The detection limit of the microchip
      MS experiment for myoglobin was found to be lower than 6 x 10(-8) M. Samples in
      75% methanol were successfully analyzed with good sensitivity, as were aqueous
      samples. The parallel mutliple-channel microchip system allowed ESI-MS analysis
      of different samples of standard peptides and proteins in one chip.

PMID- 9030054
TI  - Intermolecular interactions involved in solute retention on carbon media in
      reversed-phase high-performance liquid chromatography.
AB  - Carbon adsorbents for RPLC separations are greatly underutilized due to the poor
      chromatographic properties of the earliest commercially available materials and
      our limited understanding of solute interactions with the solid surface.
      Previously, we reported on the properties of a carbon surface prepared by vapor
      deposition on porous zirconia microspheres. The resulting material is a new type
      of carbon sorbent with considerably improved chromatographic properties. Here we
      present a fundamental study of the intermolecular interactions influencing solute
      retention on these novel carbon phases under RPLC conditions. Retention on seven
      unique carbon phases has been correlated with solute descriptors of dispersion,
      dipolarity/polarizability, and hydrogen bond basicity through the use of linear
      solvation energy relationships (LSERs). In stark contrast, conventional bonded
      phases do not show the large contribution from dipolarity/ polarizability, that
      is observed on these types of carbon. The presence of this interaction indicates
      a distinct difference between carbon and conventional bonded RPLC phases. Other
      results suggest that solvent sorption plays a significant role in controlling
      solute retention on carbon. In addition, we investigated the temperature
      dependence of retention on carbon and found typical RPLC-like behavior.

PMID- 9030057
TI  - Characterization of a tunable optical parametric oscillator laser system for
      multielement flame laser excited atomic fluorescence spectrometry of cobalt,
      copper, lead, manganese, and thallium in buffalo river sediment.
AB  - A pulsed (10 Hz) optical parametric oscillator (OPO) laser system based on beta
      barium borate (BBO) crystals and equipped with a frequency-doubling option (FDO)
      was characterized for use in laser excited atomic fluorescence spectrometry
      (LEAFS). This all-solid-state laser has a narrow spectral line width, a wide
      spectral tuning range (220-2200 nm), and a rapid, computer-controlled slew scan
      of wavelength (0.250 nm s-1 in the visible and infrared, and 0.125 nm s-1 in the
      ultraviolet). The output power characteristics (15-90 mJ/pulse in the visible, 1
      40 mJ in the infrared, and 1-11 mJ in the ultraviolet), laser pulse-to-pulse
      variability (3-13% relative standard deviation, RSD, of the laser pulses),
      conversion efficiency of the FDO (2-17%), and spectral bandwidth in the visible
      spectrum (0.1-0.3 cm-1) were measured. The laser was used as the excitation
      source for a flame LEAFS instrument for which rapid, sequential, multielement
      analysis was demonstrated by slew scan of the laser. The instrument allowed about
      640 measurements to be made in about 6 h, with triplicate measurements of all
      solutions and aqueous calibration curves, which yielded accurate analyses of a
      river sediment (National Institute of Standards and Technology, Buffalo River
      Sediment, 2704) for five elements with precisions < 5% RSD. Comparable or
      improved flame LEAFS detection limits over literature values were obtained for
      cobalt (2 ng mL-1), copper (2 ng mL-1), lead (0.4 ng mL-1), manganese (0.2 ng mL
      1), and thallium (0.9 ng mL-1) by flame LEAFS.

PMID- 9030058
TI  - Temperature and quenching studies of fluorescence polarization detection of DNA
      hybridization.
AB  - The effects of temperature and collisional quenching on fluorescence polarization
      detection of DNA hybridization were studied using measurements of fluorescence
      intensity and anisotropy and the dynamic decay of these properties. Three
      different tethers, 3, 6, and 12 carbons in length, were used to attach
      fluorescein label to the 5' end of the 33-base oligomers. Perrin plots showed
      that the effective rotating volume decreases with increasing tether length and
      approximately doubles upon hybridization. Hybridization increases the association
      between the tethered dye and the DNA for the shorter tethers but displaces the
      fluorescein on the 12C tether from the DNA, forcing it into greater contact with
      the bulk solution. The 6C tether appears to promote sequence-specific interaction
      between fluorescein label and the oligomer, which causes unexpectedly high
      anisotropy at higher temperatures and increased protection from collisional
      quenching. In all cases, there appear to exist several possible conformations for
      the tethered fluorescein. As temperature is increased, these conformations tend
      to collapse into a single, average or preferred, conformation. The results
      demonstrate the importance of the selection of tether, dye, and DNA probe in
      designing a polarization strategy for detection of DNA hybridization,
      particularly with respect to tether length and DNA probe sequence.

PMID- 9030056
TI  - Space charge evaluation in a plasma-source mass spectrograph.
AB  - Space charge effects, and the matrix interferences they cause, are problems in
      inductively coupled plasma mass spectrometry (ICPMS). It has previously been
      observed that these deleterious space charge effects are not significantly
      present in sector-field instruments, a fact that has been attributed, but not
      demonstrated, to the high accelerating potentials they commonly employ. To
      examine the significance of space charge in our plasma-source mass spectrograph
      (which operates at only moderate accelerating potentials) and in other sector
      instruments, a graphite disk was placed approximately 7 cm behind the skimmer. An
      inductively coupled plasma was operated for 17 h while a 0.01 mM multielement
      solution was introduced. This disk was then analyzed by spatially resolved laser
      ablation ICP time-of-flight MS. Second vacuum-stage acceleration appears to be an
      important factor that governs the elemental distribution within the ion beam. The
      ion beam width at m/z 208 is one-third of its width at m/z 7 using an
      accelerating potential of 800 V; at an accelerating potential of 4000 V, the ion
      beam width does not vary with mass.

PMID- 9030059
TI  - All-solid-state miniaturized fluorescence sensor array for the determination of
      critical gases and electrolytes in blood.
AB  - We describe a six-channel, all-solid-state, miniaturized fluorescence sensor
      array for the precise determination of blood analytes for medical diagnostic
      purposes. The device features superblue LEDs as light sources, GRIN optics, and
      photodiodes, assembled according to pigtailing procedures (Bruno, A. E.; et al.
      Trends Anal. Chem. 1994, 13, 190-198). The numerical aperture of the fluorescence
      optics is 0.46, rendering a collection efficiency of 2.4%. The performance of
      this instrument has been evaluated in terms of dynamic response, linearity,
      channel reproducibility, reversibility, long-term drifts, photobleaching of
      indicator, cross-talk, ionic strength, and selectivity in pH measurements. The
      responses of the pH sensing membranes were optimized in the physiological range.
      Responses are linear with typical values of approximately 1.5 V/pH units, with
      limits of decision of 24 mV, which corresponds to pH resolutions of 0.03 pH unit.
      Under continuous illumination, using calibration buffers, the sensors display
      nonstatistical differences within 2 standard deviations over a period of 6 h, and
      it is shown that, under discontinuous illumination, the membranes can be used in
      more than 2000 measurements without need of calibration, in contrast to
      electrochemical sensors which require periodic calibration. After selecting the
      appropriate combination of LEDs, excitation and emission filters, and sensing
      membranes, the instrument was used to determine the concentrations of various
      critical blood analytes in buffer solutions in the various channels. Similar
      measurements in untreated blood reproduce the reported results.

PMID- 9030060
TI  - Determination of nanograms of nucleic acids by their enhancement effect on the
      resonance light scattering of the cobalt(II)/4-[(5-chloro-2-pyridyl)azo]-1,3
      diaminobenzene complex.
AB  - Using a common spectrofluorometer to measure the intensity of resonance light
      scattering, a method for determination of nucleic acids in the nanogram range has
      been developed. In the pH range 11.5-12.0, the resonance light-scattering of the
      binary complex of cobalt(II)/ 4-[(5-chloro-2-pyridyl)azo]-1,3-diaminobenzene (5
      Cl-PADAB) is greatly enhanced by nucleic acids, with the maximum scattering peak
      located at 547.0 nm. The enhanced intensity of resonance light-scattering is in
      proportion to the concentration of calf thymus DNA in the range 0-400 ng/mL and
      to that of fish sperm DNA and yeast RNA in the range 0-300 ng/mL. The limits of
      detection are 1.4 ng/mL for calf thymus DNA, 0.8 ng/ mL for fish sperm DNA, and
      1.3 ng/mL for yeast RNA. Precision at 200 ng/mL for the three nucleic acids is
      1.9%, 2.0%, and 0.8%, respectively. Six synthetic samples were determined
      satisfactorily. Mechanism studies showed that the nature of the reaction is that
      the binary complex of Co(II)/5-Cl -PADAB reacts with single-stranded nucleic
      acid, and the enhancement effect of nucleic acids on the resonance light
      scattering of the binary complex is due to the stacking of the binary complex on
      nucleic acids, which act as a template.

PMID- 9030061
TI  - Fibromuscular dysplasia of the renal artery--rapid progression with formation of
      aneurysm: case report.

PMID- 9030062
TI  - Comparison of two-dimensional time-of-flight dynamic magnetic resonance
      angiography with digital subtraction angiography in popliteal artery entrapment
      syndrome.
AB  - OBJECTIVE: To assess dynamic magnetic resonance angiography (MRA) as an
      alternative to catheter angiography in patients with popliteal artery entrapment
      syndrome (PAES). PATIENTS AND METHODS: Nine patients with surgically proven PAES
      underwent provocation digital subtraction angiography (DSA) and 2-dimensional
      time-of-flight dynamic MRA of the popliteal fossae (total of 17 limbs). Eight
      normal volunteers also underwent dynamic MRA (total of 16 limbs). Two observers
      blinded to the surgical findings and the results of DSA independently evaluated
      the 33 limbs of the 17 subjects on the basis of maximum-intensity projection
      images and transverse MRA source images. The degree of stenosis was graded and
      compared with that indicated by DSA. RESULTS: Among the 17 limbs of patients with
      surgically proven PAES, dynamic MRA suggested the correct diagnosis in 13 (76%)
      by indicating stenosis greater than 50%. Dynamic MRA indicated stenosis of 1% to
      50% for 4 (25%) of the 16 normal limbs and no stenosis in the other 12 normal
      limbs (i.e., no false positive results). CONCLUSION: Catheter angiography is not
      necessary if dynamic MRA indicates stenosis of greater than 50% in patients with
      clinical suspicion of PAES, but is recommended if dynamic MRA indicates stenosis
      of 1% to 50%.

PMID- 9030063
TI  - Embolization of apparently normal pulmonary arteries as a treatment for
      hemoptysis: case report.

PMID- 9030064
TI  - Spontaneous knotting of a transgastric jejunostomy tube: case report.

PMID- 9030065
TI  - Aneurysmal bone cyst formation within a chondroblastoma: case report.

PMID- 9030066
TI  - Thrombosed fusiform basilar aneurysm associated with Klippel-Trenaunay-Weber
      syndrome: case report.

PMID- 9030067
TI  - Aberrant internal carotid artery presenting in the midline retropharyngeal space:
      case report.

PMID- 9030068
TI  - Selective supplementation of calcaneal ultrasound densitometry with dual-energy x
      ray absorptiometry of the spine and femur for population screening.
AB  - OBJECTIVE: To determine the limitations on the improvements in the efficacy of
      screening with ultrasound densitometry of the calcaneus that can be achieved by
      adding direct-site mineral measurements of the lumbar spine and the femur when
      the ultrasound t-score is low. SUBJECTS AND METHODS: The author retrospectively
      analysed data from 2500 women for whom the results of both dual-energy x-ray
      absorptiometry of the lumbar spine and femur and ultrasonometry of the calcaneus
      were available. Various ultrasound t-score cut-off values (from 0 to -4.5) were
      tested to determine changes in sensitivity, specificity, false negatives, false
      positives and accuracy with and without adding direct-site measurements of the
      lumbar spine and the femur neck. RESULTS: For this analysis, the addition of
      direct-site measurement data increases the specificity to 100% for all t-score
      cut-off values without affecting the sensitivity, thereby improving the accuracy;
      however, the number of false negatives remains unknown. The number of false
      negatives decreases as the cut-off value is increased, but with higher cut-off
      values, greater numbers of subjects would have to be recalled for direct-site
      measurements of the lumbar spine and the femoral neck, which would entail extra
      costs. CONCLUSIONS: The accuracy of screening for low mineral content by
      calcaneal ultrasonometry is improved by recalling subjects for direct-site
      measurements if their ultrasound t-score falls below some arbitrary value. The
      cut-off value must be chosen to achieve a balance between the number of missed
      false negatives that are acceptable in the screening process and the number of
      subjects recalled for the direct-site study at additional cost. In remote areas,
      where dual-energy x-ray absorptiometry devices for performing the supplemental
      measurement are not usually available, the cost of transportation would be
      another factor.

PMID- 9030069
TI  - Delayed excretion of radionuclide in scanning with diisopropyl iminodiacetic acid
      does not exclude the possibility of primary biliary atresia: case report.

PMID- 9030070
TI  - Inflammatory pseudotumour of the lung presenting as multiple pulmonary nodules:
      case report.

PMID- 9030072
TI  - Residents' corner. Answer to case of the month #44. Intralobar pulmonary
      sequestration in the right lower lobe.

PMID- 9030071
TI  - Granular cell tumour of the trachea: case report.

PMID- 9030073
TI  - Residents' corner. Answer to case of the month #45. Stress changes of the distal
      radial physis.

PMID- 9030075
TI  - Early hospital discharge and home care.

PMID- 9030076
TI  - Hepatoma, paroxysmal dyspnea and diaphragmatic hump.

PMID- 9030074
TI  - Mandatory exploration or observation for penetrating neck injuries?

PMID- 9030077
TI  - Radiology for the surgeon. Case 13. Giant cavernous hemangioma of the liver.

PMID- 9030078
TI  - Comparison of hemorrhoidal treatments: a meta-analysis.
AB  - OBJECTIVE: To determine whether any method of hemorrhoid therapy has been shown
      to be superior in randomized trials. METHOD: A meta-analysis of all randomized
      controlled trials assessing two or more treatment modalities for symptomatic
      hemorrhoids. MAIN OUTCOME MEASURES: Response to therapy, the need for further
      therapy, complications and pain. RESULTS: Eighteen trials were available for
      analysis. Hemorrhoidectomy was found to be significantly more effective than
      manual dilatation of the anus (p = 0.0017) and associated with less need for
      further therapy (p = 0.034), no significant difference in complications (p =
      0.60) but more pain (p < 0.001). Patients who underwent hemorrhoidectomy had a
      better response to treatment than did patients who were treated with rubber-band
      ligation (p = 0.001), although complications were greater (p = 0.02), as was pain
      (p < 0.0001). Rubber-band ligation was better than sclerotherapy in response to
      treatment for all hemorrhoids (p = 0.005) and for hemorrhoids stratified by grade
      (grades 1 and 2, p = 0.007, grade 3, p = 0.042), with no difference in the
      complication rate (p = 0.35). Patients treated with sclerotherapy (p = 0.031) or
      infrared coagulation (p = 0.0014) were more likely to require further therapy
      than those treated with rubber-band ligation, although pain was greater after
      rubber-band ligation (p = 0.03 for sclerotherapy, p < 0.0001 for infrared
      coagulation). CONCLUSIONS: Rubber-band ligation is recommended as the initial
      mode of therapy for grades 1 to 3 hemorrhoids. Although hemorrhoidectomy showed
      better response, it is associated with more complications and pain than rubber
      band ligation. Thus, it should be reserved for patients whose hemorrhoids fail to
      respond to rubber-band ligation.

PMID- 9030079
TI  - Group A Streptococcus invasive infections: a review.
AB  - The incidence of group A Streptococcus (GAS) invasive infections has been
      increasing worldwide, and there is no obvious explanation for this phenomenon. In
      1993, a working group on severe GAS infections was established to define
      accurately what constitutes an invasive infection. Three types of infection are
      particularly feared: necrotizing fasciitis, myositis and a newly defined entity,
      named streptococcal toxic shock syndrome (STSS) because of a certain analogy with
      its staphylococcal counterpart. GAS produces many toxins responsible for its
      clinical manifestations. Some of them, labelled streptococcal pyrogenic
      exotoxins, have been characterized as superantigens. These proteins play a key
      role in initiating the immune response to GAS and are mostly responsible for the
      precipitous course of invasive infections. Death rates are high in streptococcal
      invasive infections, ranging from about 20% for necrotizing fasciitis to almost
      100% for myositis. Therapy consists mainly of high doses of antibiotic
      combinations, aggressive surgery, and intravenous administration of
      immunoglobulins for STSS.

PMID- 9030080
TI  - Impact of infection by verotoxigenic Escherichia coli O157:H7 on the use of
      surgical services in a children's hospital.
AB  - OBJECTIVES: To determine the impact of Escherichia coli O157:H7 infection in
      children on the need for surgical assessment in a pediatric surgical practice and
      whether clinical and bacteriologic variables might contribute to that need.
      DESIGN: Examination of a case series. SETTING: A tertiary-care pediatric
      hospital. PATIENTS: Between 1990 and 1994, E. coli O157:H7 gastrointestinal
      infections were documented among 85 children, 29 of whom suffered from hemolytic
      uremic syndrome. INTERVENTION: Surgical consultation for presumed or proven
      complications of the infection. MAIN OUTCOME MEASURES: The frequency of and
      reasons for surgical consultation, clinical and bacteriologic variables between
      patients who did or did not require surgical assessment. RESULTS: Of the 85
      children, 17 (20%) were assessed by the surgical service. The majority of these
      children were inpatients. Two required abdominal surgery. Female gender, older
      age and progression to hemolytic-uremic syndrome were factors associated in
      univariate analyses with a likelihood of need for surgical assessment; variation
      in bacterial genotype was not. CONCLUSION: There is the potential for
      verotoxigenic E. coli O157:H7 infection to have a considerable impact on the
      utilization of pediatric surgical services.

PMID- 9030081
TI  - Penetrating and blunt neck trauma: 10-year review of a Canadian experience.
AB  - OBJECTIVES: To determine if selective management of blunt and penetrating neck
      trauma is still appropriate in Canadian tertiary care centres because of
      differences in trauma demographics. A key secondary objective was a descriptive
      analysis of the Canadian head and neck trauma patient population and outcomes.
      DESIGN: A retrospective case series. SETTING: An academic tertiary care centre.
      PATIENTS: All 85 patients admitted between 1982 and 1992 with a diagnosis of
      blunt (19) or penetrating (66) neck trauma. INTERVENTIONS: Emergent neck
      explorations (29 patients), selective nonoperative management (20 patients) and
      elective neck exploration (17 patients). MAIN OUTCOME MEASURES: Hospital stay,
      complication rate, rate of negative exploration (elective management, emergent
      exploration) and rate of secondary exploration (selective management), and
      outcome and complication rate. The entire population was described
      demographically. RESULTS: In 66 patients the injuries were penetrating, with the
      majority being of low kinetic energy. The patients who underwent elective
      mandatory exploration were comparable to those who underwent selective
      nonoperative management. The length of stay in hospital for the selective group
      was significantly less (p = 0.0008), and no patient in this group required later
      operative management of a missed injury. However, 41% of patients who underwent
      elective mandatory neck exploration had no significant injury. The complication
      rate in the two groups was similar. CONCLUSIONS: The patients managed selectively
      had no difference in outcome from those who underwent mandatory elective
      exploration. In Canada, because of the lower incidence of high-morbidity zone I
      and zone III injuries and the high incidence of low kinetic energy trauma with a
      predilection to zone II, the surgeon may consider a selective approach where
      appropriate.

PMID- 9030082
TI  - Caremap management for postoperative prostatectomy care at home: a comparative
      study.
AB  - OBJECTIVE: To evaluate early discharge from hospital with community-based care as
      an alternative to hospital-based care for patients who have undergone
      transurethral resection of the prostate (TURP). DESIGN: Prospective comparative
      study. SETTING: A major urban hospital and the urban community. PATIENTS: Of 198
      patients who underwent TURP between Jan. 10, 1994 and Sept. 30, 1994, 81,
      discharged on postoperative day 1, received the caremap method of health care
      delivery at home. They were compared with 85 patients who were discharged on
      postoperative day 2 or 3 and received standard hospital-based care. MAIN OUTCOME
      MEASURES: Readmission to hospital, reuse of health care services, complications
      and patient satisfaction. RESULTS: Comparison of the 2 groups revealed no
      significant differences in readmissions to hospital, reutilization of health care
      services or complications. Following these initial results, the early discharge
      program was expanded to include all acute care hospitals and the surrounding
      community. CONCLUSIONS: Postoperative care for TURP can be delivered in the home.
      A critical success factor was the ability to provide quality care in the
      community without adverse effects.

PMID- 9030083
TI  - The surgical and oncologic significance of the axillary arch during axillary
      lymphadenectomy.
AB  - An uncommon and often-overlooked anatomic variation of the latissimus dorsi
      muscle is the axillary arch. It is formed by an anomalous slip of the muscle that
      arises from the body of the latissimus dorsi but then inserts along with the
      pectoralis major muscle anterior to the axillary vein and neurovascular bundle.
      If an axillary arch is encountered during axillary lymphadenectomy, the lymph
      nodes posterior and lateral to the arch should be excised. Experience with a
      number of cases is used to consider local therapeutic and staging factors.

PMID- 9030084
TI  - Osteomyelitis of the spine due to Salmonella infection--conservative treatment
      with quinolone: a case report.
AB  - Although osteomyelitis due to Salmonella infection is known to be associated with
      sickle cell anemia, various hemoglobinopathies and immune suppressive states, it
      may also occur in normal hosts. A 16-year-old Chinese boy without sickle cell
      disease or any other condition that would compromise the immune system had
      osteomyelitis of the lumbar spine caused by Salmonella enteritidis. The condition
      was treated conservatively with ciprofloxacin (quinolone group). This may be the
      first reported case in which a patient with spinal osteomyelitis due to
      Salmonella infection, who was otherwise healthy, was successfully treated
      nonoperatively with quinolone.

PMID- 9030085
TI  - Sarcoma of bone-cement membrane: a case report and review of the literature.
AB  - The development of a cancerous tumour at the site of total joint replacement is a
      rare but virtually always fatal event. The previously unreported scenario of a
      patient who was found to have a malignant fibrous histocytoma at the bone-cement
      membrane after revision for a loose total hip prosthesis is reported. Recent
      biologic information evaluating the response of mesenchymal cells to metallic
      debris suggests that the environment surrounding a loosened prosthesis may
      provide conditions appropriate for the development of a sarcoma.

PMID- 9030086
TI  - A rare case of hip dislocation after internal fixation of a femoral neck fracture
      without infection.
AB  - Hip dislocation after hip pinning has been reported in association with sepsis,
      but in this paper the authors describe a case of gradual, spontaneous dislocation
      of the hip over several weeks, without sepsis, in a 36-year-old man who had
      undergone screw-plate fixation of a displaced basi-cervical fracture. This is
      only the second reported case of spontaneous dislocation after hip pinning not
      associated with infection.

PMID- 9030087
TI  - Mobile tumours in the lumbar spinal canal: a diagnostic problem.
AB  - In two cases of mobile tumours in the lumbar spinal canal there was difficulty
      and delay in clinical and radiologic diagnosis because the early symptoms did not
      correspond to any particular dermatome. Myelography and computed tomography (CT)
      are the initial diagnostic procedures used in most institutions, even where
      magnetic resonance imaging (MRI) is available. The purpose of these 2 case
      reports is to remind clinicians that it is possible for certain tumours attached
      to the roots in the lumbar spinal canal to migrate, because the roots tend to be
      redundant or tax. Multilevel search is essential in neuroradiologic studies for
      early diagnostic confirmation of mobile tumours.

PMID- 9030088
TI  - Spontaneous internal herniation through the foramen of Winslow: a case report.
AB  - A 41-year-old woman, who presented with acute onset of generalized peritonitis,
      was found to have a segment of strangulated small bowel incarcerated in the
      lesser peritoneal sac through the foramen of Winslow. The strangulated small
      bowel was reduced and resected. The predisposing factors for this condition as
      mentioned in the literature were not present in this case. In particular, the
      herniation was associated with a small foramen of Winslow and the presentation
      was one of rapidly developing peritonitis.

PMID- 9030089
TI  - Antigen presentation of mucosal pathogens: the players and the rules.
AB  - A vast number of infectious pathogens gain entry into the host through mucosal
      surfaces, which have a much greater total surface area than the skin. Since the
      mucosa is continuously exposed to those pathogens, the development of an
      effective local immune response is of utmost importance. An obligatory step in
      the development of most immune responses is the presentation of antigens by
      specialized accessory cells, termed antigen-presenting cells (APC) to T
      lymphocytes. The recognition of antigens by T cells is largely determined by how
      the antigens are handled by the APC. Complex antigen-processing events generate a
      selected set of peptides which ultimately become associated with MHC molecules.
      The type of MHC molecules that bind the peptides in turn determine what T
      lymphocyte subset recognizes the peptides. Thus, an understanding of the
      molecular and cellular processes preceding the T cell recognition event is a
      prerequisite for understanding how mucosal immune responses develop, as well as
      for investigating alternative approaches to vaccine development and therapeutic
      strategies to control autoimmune diseases. This review discusses the cell biology
      of antigen processing and how various APC populations may participate in mucosal
      responses.

PMID- 9030090
TI  - Role of hemolytic and nonhemolytic phospholipase C from Pseudomonas aeruginosa
      for inflammatory mediator release from human granulocytes.
AB  - BACKGROUND: Pseudomonas aeruginosa phospholipase C (PLC) is a critical component
      in the pathogenesis of severe P. aeruginosa infections. However, P. aeruginosa
      can produce a hemolytic (PLC-H) as well as a nonhemolytic (PLC-N) variant, both
      having a MW of about 77 kD. In the past, studies did not distinguish between both
      types of PLC with regard to the induction of inflammatory mediators from human
      cells. METHODS: We compared the ability of P. aeruginosa PLC-H and PLC-N to
      generate leukotriene B4 (by HPLC) and oxygen (O2-) metabolites (luminol-enhanced
      chemiluminescence), and to release beta-glucuronidase and histamine
      (fluorophotometry from human granulocytes. Therefore, human neutrophilic
      granulocytes (PMN; 1 x 10(7)) or human peripheral blood mononuclear cells (5 x
      10(6)) were treated with purified P. aeruginosa PLC-H (up to 10 units) as well as
      culture supernatants (cutoff: MW > 50,000) of P. aeruginosa PAOl capable of
      producing both PLC-H and PLC-N, and PAOl mutant strains deficient in the
      production of either or both phospholipases. Controls were PLC-H from Clostridium
      perfringens and PLC-N from Bacillus cereus. RESULTS: PLC-H-containing P.
      aeruginosa culture supernatant, purified P. aeruginosa PLC-H as well as PLC-H
      from P. perfringens activated human leukocytes for a significant (p < 0.05)
      increase in inflammatory mediator release. In this regard, purified PLC-H (10
      units) from P. aeruginosa activated human PMN for a significant increase in the
      generation of oxygen metabolites (30 +/- 5.4 x 10(3) cpm) and in leukotriene B4
      (6.1 +/- 2.0 ng), in the release of beta-glucuronidase (15.8 +/- 1.1%) and of
      histamine (25.8 +/- 6.2%) as compared to the corresponding control values (3 +/-
      1 x 10(3) cpm; 0.2 +/- 0.1 ng; 5.1 +/- 1.0%, 5.1 +/- 1.5%). Culture supernatants
      containing no PLC or only PLC-N, as well as PLC-N from B. cereus, failed to
      activate or only slightly stimulated human granulocytes for inflammatory mediator
      release. CONCLUSION: The data thus provide evidence that P. aeruginosa PLC-H can
      be a potent inducer of inflammatory mediator release, at least in vitro. Our
      results therefore contribute to the understanding of the pathophysiological role
      of P. aeruginosa PLCs.

PMID- 9030091
TI  - Immunostimulatory effects of platinum compounds: correlation between sensitizing
      properties in vivo and modulation of receptor-mediated endocytosis in vitro.
AB  - The sensitizing properties of different complex salts of platinum were defined in
      vivo by means of the popliteal lymph node (PLN) assay in mice. Hexa- and
      tetrachloroplatinates were confirmed to be highly immunogenic, inducing vigorous
      primary immune responses in the draining PLN following single subcutaneous
      injections. Flow-cytometric analysis revealed a dramatic increase in the total
      number of cells expressing proliferating cell nuclear antigen. The majority of
      these cells were of the T helper phenotype (CD4+) reflecting the T-cell
      dependence of the PLN response induced by Pt salts such as Na2[PtCl6] or
      Na2[PtCl4]. In contrast, [Pt(NH3)4]Cl2 failed to elicit a significant increase in
      PLN cell proliferation when compared with saline-treated controls. The
      differential immunogenicity of the Pt compounds found in vivo directly correlated
      with their capacity to modulate mechanisms of receptor-mediated endocytosis in
      murine Langerhans cells in vitro. The reactivity of Na2[PtCl6] or Na2[PtCl4]
      resembled that of potent contact sensitizers in this endocytosis assay whereas
      [Pt(NH3)4]Cl2 proved to be mert. These results suggest that [Pt(NH3)4]Cl2 might
      be less harmful to humans than hexa- or tetrachloroplatinates. As demonstrated
      with Pt compounds, monitoring of direct effects of low-molecular-weight chemicals
      on antigen-presenting dendritic cells in vitro is able to predict their
      sensitizing potential in vivo.

PMID- 9030092
TI  - Flow-cytometric analysis of T-cell receptor expression in peripheral blood
      lymphocytes.
AB  - BACKGROUND: Lymphocytes of subjects sensitized to the insect-derived allergen Chi
      t 1-9 are, in response to the allergen, characterized by an elevated
      proliferation and increased expression of activation markers such as HLA-DR and
      CD25 in vitro. A restriction for HLA-DR B1 in monosensitized patients was found.
      OBJECTIVE: The aim of this study was to investigate whether the response to the
      allergen Chi t 1-9 involves the preferential cell surface expression of a
      specific alpha/beta T-cell receptor type. METHODS: The T-cell receptor repertoire
      was measured with 7 monoclonal antibodies to epitopes on the variable region of
      the alpha- and beta-chain by flow cytometry. Cell lines of 9 patients were
      established with Chi t 1-9, 6 with tetanus toxoid and 6 with phytohaemagglutinin
      in the presence of interleukin 2. In addition, non-stimulated lymphocytes as well
      as lymphocytes of 5 non-sensitized controls exposed to Chi t 1-9 were examined.
      RESULTS: Each of the 9 sensitized and 5 control subjects studied showed an
      individual pattern of lymphocyte expression for each T-cell receptor specificity.
      However, after stimulation specific to Chi t 1-9 for 2 weeks, a significant
      increase in V beta 8-expressing cells was measurable only in patients sensitized
      to Chi t 1-9. The cells of the 5 control subjects showed no significant changes
      due to the allergen stimulation. CONCLUSION: These data suggest that the
      expression of certain T-cell receptor types plays an important role in the
      development of Chi t 1-9 allergy.

PMID- 9030093
TI  - Detection and characterisation of anti-endomysial antibody in coeliac disease
      using human umbilical cord.
AB  - OBJECTIVES: To verify the effectiveness of human umbilical cord (HUC) in the
      detection of anti-endomysial antibodies (AEA) in coeliac disease and to
      characterize further these antibodies by studying tissue adsorption
      characteristics and antibody inhibition studies. METHODS: AEA were detected on
      HUC and primate oesophagus in a blind study, using sera from 46 patients with
      untreated coeliac disease and 108 controls. Tissue adsorption studies were
      performed using homogenized tissue from rodent liver, HUC, primate oesophagus and
      human liver. Sera were adsorbed with each of these homogenates and antibody was
      detected using HUC, primate oesophagus and rat kidney. In the inhibition
      experiments AEA was detected on HUC, and inhibition of binding was attempted by
      pre-incubating the sections with antibodies against collagen types I, III and IV.
      RESULTS: The sensitivity of AEA was 91% when detected on HUC, 89% when detected
      on primate oesophagus (93% and 91%, respectively, after exclusion of 1 patient
      with IgA deficiency). Specificity was 100% for both assays. Tissue adsorption
      studies showed identical results for AEA detected on both HUC or primate
      oesophagus, whereas antireticulin antibody was adsorbed only by rodent tissue.
      Blocking of the HUC with anticollagen antibodies did not prevent binding of AEA.
      CONCLUSIONS: HUC is an effective substrate for the detection of AEA and may be
      superior to primate oesophagus. The antibody detected by HUC shows identical
      tissue adsorption specificities to that detected on primate oesophagus.

PMID- 9030094
TI  - Differing regulation of major histocompatibility class II and adhesion molecules
      on human umbilical vein endothelial cells by serotonin.
AB  - Major histocompatibility class II molecules (MHC class II), whose biosynthesis
      and expression by endothelial cells can be induced by gamma-interferon (IFN
      gamma), play a major role in antigen recognition and subsequent cell-cell
      interactions involved in the initiation of immune responses. Adhesion molecules
      such as E-selectin and intercellular adhesion molecules (ICAM-1), whose
      biosynthesis and membrane expression by endothelial cells is regulated by
      proinflammatory cytokines (IL-1 and TNF), are necessary for the attachment and
      subsequent extravasation of leukocytes into the surrounding tissue. In the
      present study, the effects of preformed inflammatory mediators (histamine and
      serotonin) on the induction and expression of MHC class II, E-selectin, and ICAM
      1 molecules by human umbilical vein endothelial cells were examined. Serotonin
      but not histamine was found to significantly inhibit in a dose-response fashion
      the induction and expression of MHC class II molecules. Inhibition occurred when
      it was added 24 h before, at the same time (most effective), or 24 h after IFN
      gamma stimulation. No enhancement or stimulation of MHC class II biosynthesis
      could be detected using moderate or low concentration of either histamine or
      serotonin alone. In contrast to MHC class II molecules, neither serotonin nor
      histamine blocked the induction and biosynthesis of E-selectin and ICAM-1
      molecules as detected by specific H18/7 and RR1/1 monoclonal antibodies,
      respectively, using flow cytometry. These findings suggest that serotonin but not
      histamine can assist in regulating the induction and expression of MHC class II
      molecules. Failure to block biosynthesis of E-selectin and ICAM-1 induced by TNF
      alpha and IL-1 beta indicates the inhibitory effect exerted by serotonin was
      selective in nature.

PMID- 9030095
TI  - High levels of circulating interleukin-4 and interleukin-10 in Kawasaki disease.
AB  - For analysis of the cytokine network in Kawasaki disease (KD), we measured over
      time the plasma levels of interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 in
      patients with KD. Fifteen patients with KD were studied. Eight healthy children
      were selected as control subjects. Circulating IFN-gamma levels were measured by
      immunoradiometric assay, and IL-4 and IL-10 levels were measured by enzyme-linked
      immunosorbent assay. The results were as follows: (1) The plasma levels of IFN
      gamma in KD patients in the acute phase were significantly higher than the levels
      of patients in the convalescent phase (p < 0.05) and those of the control
      children (p < 0.05). (2) The plasma levels of IL-4 in the KD patients in the
      acute phase were significantly higher than the levels of the patients in the
      convalescent phase (p = 0.001) and those of the control children (p = 0.001). (3)
      The plasma levels of IL-10 in the KD patients in the acute phase were
      significantly higher than the levels of the patients in the convalescent phase (p
      < 0.03) and those of the control children (p < 0.005). (4) The investigation of
      the relationship between the IL-4 and IFN-gamma levels during the acute phase of
      KD demonstrated a significant reciprocal relationship (p < 0.05). (5) There was
      no significant relationship between the IL-4 and IL-10 levels during the acute
      phase. However, plasma IL-10 levels were low in the patients with high levels of
      plasma IL-4, and the patients with high levels of IL-10 revealed low levels of
      plasma IL-4. The above results suggested that a variety of patterns of cytokine
      production was present in the acute phase of this disease, and that the key
      cytokine, which might regulate the cytokine network, was IL-4.

PMID- 9030096
TI  - Inhibition of neutrophil elastase-induced interleukin-8 gene expression by
      urinary trypsin inhibitor in human bronchial epithelial cells.
AB  - BACKGROUND: Urinary trypsin inhibitor (UTI), a potential inhibitor for
      proteinases including neutrophil elastase (NE), trypsin, plasmin, cathepsin B and
      H has been used for the treatment of lung diseases with the absence of side
      effects in Japan. METHODS: In this study, we investigated the inhibitory effects
      of UTI on both purified NE and NE activities present in bronchoalveolar fluids
      from patients with chronic bronchitis. We also investigated the inhibitory
      capacity of UTI with regard to NE-induced interleukin-8 gene expression in human
      bronchial epithelial cells by Northern analyses. RESULTS: UTI inhibited NE
      activities in bronchoalveolar lavage fluid from patients with chronic bronchitis
      and of the purified enzyme. In addition, UTI inhibited NE-induced interleukin-8
      gene expression and protein secretion in a human bronchial epithelial cell line.
      CONCLUSIONS: Our results suggest that UTI is applicable to patients with a
      variety inflammatory lung diseases in which NE plays a pivotal role.

PMID- 9030097
TI  - Combinations of IgE values and lymphocyte proliferative responses for
      consideration of the clinical course of infantile hen's-egg-sensitive atopic
      dermatitis.
AB  - We have attempted a new approach, using peripheral blood mononuclear cells
      (PBMCs), to predict the clinical course of infantile food-sensitive atopic
      dermatitis (AD). In this study, we investigated the relationships between the
      clinical course of infantile hen's-egg-sensitive AD and laboratory data obtained
      at the early stage of AD, particularly on combinations of specific IgE antibodies
      to hen's egg and proliferative responses of PBMCs to ovalbumin (OA). Total IgE
      concentrations, specific IgE antibodies to hen's egg and proliferative responses
      of PBMCs to OA were measured in 31 hen's-egg-sensitive AD patients within 6
      months after development of AD symptoms. After the acquisition of laboratory
      data, the clinical courses of all patients were followed up for 1 year. The
      stimulation index of proliferative responses of PBMCs to OA in hen's-egg
      sensitive AD patients whose symptoms did not improve was significantly (p < 0.05)
      higher than that in hen's-egg-sensitive AD patients whose symptoms improved. On
      the other hand, the radioallergosorbent test (RAST) scores for hen's egg were not
      statistically different between the two groups. The degree of refractoriness of
      AD symptoms tended to be higher in the patients who showed a higher total IgE
      concentration at the beginning of the clinical course than in those who showed a
      lower one. These results might be attributed to the underlying cause of AD, i.e.,
      a cell-mediated and an IgE-mediated allergy. We concluded that, in addition to
      total IgE concentrations, combinations of RAST values and lymphocyte
      proliferative responses to OA are important to predict the clinical course of
      infantile hen's-egg-sensitive AD.

PMID- 9030098
TI  - Characterization of Aedes communis, Aedes aegypti and Anopheles stephensi
      mosquito saliva antigens by immunoblotting.
AB  - BACKGROUND: Mosquito bites cause immediate wheals and delayed bite papules in
      sensitized subjects having saliva-specific IgE and IgG4 antibodies. At present,
      mosquito saliva antigens are not well characterized. METHODS: To identify
      immunogenic proteins in mosquito saliva and study their cross-reactivity we
      immunized mice with Aedes communis, Aedes aegypti and Anopheles stephensi bites.
      Immune sera were used in immunoblotting and immunoblot inhibition experiments.
      RESULTS: The main A. communis saliva antigens were 22-, 30-, and 36-kD, A.
      aegypti saliva antigens 31-, 36-, 46- and 64- to 66-kD, and A. stephensi saliva
      antigen 46-kD proteins. Most of the saliva antigens appeared to be species
      specific and only weak cross-reactivity was observed with heterologous immune
      sera. Distinct cross-reactivity was observed only between saliva proteins of A.
      communis and Aedes punctor, two taxonomically closely related species. Human IgE
      and IgG4 antibodies from mosquito-bite-sensitive children bound to the same
      saliva proteins as antibodies from the immunized animals. CONCLUSIONS: This study
      disclosed several immunogenic proteins in Aedes and Anopheles mosquito saliva and
      suggests that these proteins can also be allergenic in man.

PMID- 9030099
TI  - Total and birch pollen-specific human IgE in mice with severe combined
      immunodeficiency transplanted with human peripheral blood lymphocytes: donor
      dependence, seasonal variation and in vivo half-life.
AB  - BACKGROUND: There is a need for animal in vivo models in the study of human
      allergy. The aim of the present experiments was to study production and
      catabolism of human IgE in mice with severe combined immunodeficiency
      transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice). METHODS:
      Groups of SCID mice were transplanted intraperitoneally with hu-PBL from the same
      three donors in five experiments. Subgroups of transplanted mice were immunized
      with birch pollen. Production of human total and birch pollen-specific IgE in the
      hu-PBL-SCID mice was analyzed over a 7-week period. RESULTS: Human IgE was
      detected in 93% of the hu-PBL-SCID mice, and the production showed reproducible
      donor-dependent kinetics. Production of birch pollen-specific human IgE, however,
      was seen only in mice transplanted with cells from birch pollen-allergic donors.
      A greater proportion of the mice produced specific IgE when the experiment was
      started in, or some months after a birch pollen season with high pollen counts.
      The half-lives of passively transferred human IgE were determined to be 24.0 and
      23.4 h for total and birch pollen-specific IgE, respectively. CONCLUSIONS: This
      study demonstrates that human IgE production in hu-PBL-SCID mice is very
      reproducible when the same donor is used several times. Specific IgE production
      in recipient mice seems to require the use of cell donors with the actual
      specific allergy, and is most readily obtained during or after a period of donor
      allergen exposure. The short half-lives found indicate that hu-PBL-SCID mice have
      a high ongoing production of human IgE.

PMID- 9030100
TI  - Grass immunotherapy induces inhibition of allergen-specific human peripheral
      blood mononuclear cell proliferation.
AB  - The peripheral blood mononuclear cells (PBMC) from humans allergic to grass
      pollens (GR+ subjects) show strong in vitro proliferative responses to purified
      allergens from Lolium perenne pollen Lol p 1, and to a lesser extent to Lol p 2
      and Lol p 3. By contrast, PBMC from grass allergic patients undergoing
      immunotherapy (GR + IT subjects) exhibit a very poor Lol p-specific proliferative
      response, similar to that observed in nongrass allergic subjects (GR-subjects).
      Unlike GR-subjects, both GR+ and GR + IT subjects have high levels of antigen
      specific serum IgG and IgE antibodies to Lol p 1, Lol p 2 and Lol p 3. While GR+
      subjects exhibit a significant correlation between antigen-specific serum
      antibody and PBMC responses, GR + IT subjects do not show a correlation between
      the two responses. The possible mechanisms by which immunotherapy may modulate
      allergen-specific T cell proliferative response are discussed.

PMID- 9030101
TI  - Interaction of ozone and allergen challenges on bronchial responsiveness and
      inflammation in sensitised guinea pigs.
AB  - BACKGROUND: Environmental pollutants such as ozone may interact with airway
      responses to allergen in sensitised individuals. METHODS: We examined the effects
      of a single exposure to ozone (1 ppm for 1 h) on bronchial responsiveness to
      acetylcholine (ACh) aerosol 3 and 24 h after single ovalbumin (OA) challenge in
      OA-sensitised anaesthetised guinea pigs. Broncho-alveolar lavage (BAL) was
      performed and protein content and differential cell counts were determined.
      RESULTS: Ozone increased bronchial responsiveness at 3 h but not at 24 h, while
      OA alone had no effect. At 3 h after ozone, OA induced further, but non
      significant increases in bronchial responsiveness to ACh, but at 24 h after
      ozone, there was enhanced responsiveness. Neutrophil counts in BAL fluid
      increased at 3 and 24 h after exposure to ozone alone, but there were no further
      increases with ozone followed by OA exposure. Protein concentration was
      significantly increased in the ozone and OA groups at 3 and 24 h (163.4 +/- 25.6
      and 128.7 +/- 7.4 mg/ml, respectively) compared to 54.0 +/- 18.1 mg/ml in the
      control group (p < 0.02 and p < 0.01, respectively). CONCLUSION: Our data
      demonstrate an interaction of OA with ozone exposure on bronchial responsiveness;
      one underlying mechanism could be through damage at the endothelial-epithelial
      barrier.

PMID- 9030102
TI  - Effect of maturation on allergen-induced airflow obstruction and airway plasma
      exudation in sensitized guinea pigs.
AB  - Airway reactivity to bronchoconstrictor mediators changes with age. We studied
      the effects of maturation on airway responses provoked by allergen challenge
      [ovalbumin (OA) 0.05, 0.15 and 0.5 mg/kg i.v] in passively sensitized immature
      (190 +/- 2 g: 2 weeks old) and adult guinea pigs (566 +/- 16 g: 13 weeks old). In
      both groups of animals, we measured both lung resistance (RL) to monitor airflow
      obstruction and extravasation of Evans blue dye, to quantify airway plasma
      exudation. Immature guinea pigs required a larger dose of OA at the challenge to
      induce a significant increase in RL and extravasation of Evans blue dye compared
      with adult guinea pigs. In addition, immature animals responded less to the lower
      doses of OA than adults. Pretreatment with pyrilamine, an antihistamine,
      suppressed the increase in RL in immature animals, whereas the remaining
      component of the increase in RL was seen in adult animals. Intravenous allergen
      challenge causes less airflow obstruction and airway plasma exudation in immature
      than in adult guinea pigs. Allergen-induced airflow obstruction is mediated
      mainly via histamine in immature animals, whereas this may not be the case in
      adult animals.

PMID- 9030103
TI  - Effect of HIV infection on leprosy: a three-year survey in Bamako, Mali.
AB  - From February 1992 until June 1994, all patients with histologically proven
      leprosy examined at the Leprology Unit of the Institut Marchoux in Bamako, Mali,
      were screened for HIV serology. In total, 740 leprosy patients have been tested;
      553 known, previously treated leprosy cases and 187 new cases, mainly self
      reporting and referred cases. The global seroprevalence in the sample was 1.5%
      (11/740), and increased from 1.3% in 1992 to 3.1% in 1994. HIV seroprevalence was
      higher in paucibacillary (PB) than in multibacillary (MB) cases (3.8% versus
      0.8%, p < 0.05), and was slightly higher in new cases than in known, already
      treated cases (2.1% versus 1.3%), although not significantly. Among the 553
      known, already treated leprosy patients, 1 out of 7 HIV-seropositive patients
      relapsed, as opposed to 34 out of 546 HIV-seronegative cases (14.2% versus 6.2%,
      p = 0.36). Among the new cases, none of the 37 patients with reaction and/or
      neuritis was HIV positive. In known, treated leprosy cases, there was no
      difference in the frequency of reactions and/or neuritis between HIV-positive and
      HIV-negative cases. Migration in a neighboring country appeared to be a risk
      factor for HIV seropositivity in our sample (chi 2 = 4.5, p = 0.04). In order to
      estimate the association of HIV with leprosy as compared to the general
      population, a control group of blood donors was set up, matched for age and sex.
      There was, however, no difference in HIV seroprevalence between the control group
      (9/735, 1.2%) and the leprosy group (1.5%). Although leprosy patients recruited
      for this study constitute a highly selected sample, it appears that HIV infection
      has little effect on leprosy, particularly on the PB/MB ratio, leprosy reactions
      and neuritis, but there is a suggestion the HIV infection might be associated
      with increased frequency of relapse.

PMID- 9030104
TI  - Short-term follow up of patients with multibacillary leprosy and HIV infection.
AB  - During a period of 9 years, four male patients with HIV and Hansen's disease were
      detected in Tamil Nadu, South India. The sequence as to which infection came
      first is not known. All had high-risk sexual behavior with commercial sex workers
      and a past history of genital ulcer disease. Their spectrum of leprosy was
      multibacillary. Patient no. 1 had pure neural leprosy of the lepromatous type,
      which is rare. He also had a single episode of type 1 reaction which did not
      require steroid therapy. Despite having taken inadequate treatment, patient no. 2
      remained clinically and bacteriologically quiescent after 4 years of follow up.
      He had a low CD4 count of 330 cells/mm3. The third patient completed a full
      course of multibacillary multidrug therapy, and a year later is clinically and
      bacteriologically inactive. The fourth patient died of AIDS within 2 months of
      the dual diagnosis.

PMID- 9030105
TI  - Use of NASBA RNA amplification for detection of Mycobacterium leprae in skin
      biopsies from untreated and treated leprosy patients.
AB  - This study was performed to assess the value of NASBA RNA amplification of a 16S
      rRNA target for the detection of presumably viable Mycobacterium leprae in
      sections of skin biopsies from leprosy patients. The NASBA positivity rate was
      90.4% (84/93) for untreated multibacillary (MB) patients [bacterial index (BI) >
      or = 2] and 16.7% (8/48) for the untreated paucibacillary (PB) patients (BI < 2).
      NASBA positivity showed a good concordance with the presence of solidly stained
      M. leprae [morphological index (MI)] in skin biopsies from leprosy patients, but
      no relationship could be demonstrated between the strength of the NASBA signals
      and the BI. Furthermore, the usefulness of the detection of 16S rRNA by NASBA to
      monitor the efficacy of leprosy treatment was investigated using an additional
      154 biopsy specimens analyzed from 80 MB patients during the course of treatment.
      The NASBA positivity rate declined during treatment. A significant decrease was
      observed after only 1-3 months. These results favor the view that detection of
      RNA by NASBA may reflect the viability of M. leprae.

PMID- 9030106
TI  - Polymerase chain reaction of nasal swabs from tuberculosis patients and their
      contacts.
AB  - Previous studies have found Mycobacterium leprae in nasal swabs from leprosy
      patients, their contacts, and persons living in endemic areas. It might be
      expected that M. tuberculosis would be present on nasal mucosa of pulmonary
      tuberculosis patients, but whether they can be detected in patients or contacts
      is unknown. We used the polymerase chain reaction (PCR) technique on nasal swabs
      from tuberculosis patients, contacts of tuberculosis patients, leprosy patients,
      and London controls to look for both M. tuberculosis and M. leprae. Swabs dipped
      in sputum specimens from smear-positive patients were used as positive controls.
      The PCRs were conducted in two independent laboratories. M. tuberculosis was
      detected in nasal swabs from 6/16 smear-positive tuberculosis patients and from
      1/10 household contacts by one of the laboratories. All of the sputum swabs were
      positive for M. tuberculosis, and all of the London controls were negative. M.
      leprae were found in nasal swabs from 2/5 leprosy patients, but one laboratory
      also reported M. leprae in swabs from 4/21 tuberculosis patients and from one
      sputum specimen. The results show that M. tuberculosis can be found in the noses
      of some tuberculosis patients, and suggest that the bacilli also may be detected
      in some household contacts. The comparisons with M. leprae and between the two
      laboratories give further insights into the sensitivity and specificity of the
      technique.

PMID- 9030107
TI  - Detection of M. leprae by gene amplification; combined ethidium-bromide staining
      and probe hybridization.
AB  - Biopsy and skin-scraping specimens from 130 leprosy cases across the disease
      spectrum (56 TT/BT/I, 73 BB/BL/LL, and 1 neuritic case) and 50 healthy contacts
      were studied to assess the application of gene amplification. The nucleic acids
      from these clinical specimens were extracted by an integrated freeze-thawing-
      optimized lysozyme-/proteinase-k treatment-purification and fractionation
      procedure. The nucleic acids from cultured organisms were isolated by the
      stepwise procedure earlier standardized at this laboratory. Gene amplification
      for a 360-bp fragment of the 18-kDa protein gene was carried out using primer and
      the procedure described by its developers, and a 360-bp fragment on Southern blot
      was taken as the yardstick of positivity. The polymerase chain reaction product
      was analyzed by electrophoresis, ethidium-bromide (EB) staining, and blot (B)
      hybridization. Overall sensitivity ranged from 71% in specimens with undetectable
      acid-fast organisms to 100% in specimens with demonstrable acid-fast bacilli. A
      positivity of 73% in TT/BT/I specimens and 93% in BB/BL/LL specimens was
      observed. Four combinations were discerned: EB+, B+ (71%); EB-suspicious, B+
      (14%); EB-, B+ (3%) and EB-, B- (12%). By combining the blot hybridization with
      EB staining, the sensitivity could be significantly improved as compared to EB
      staining alone. The test was found to be absolutely specific by the absence of
      any false positivity in control specimens as well as with purified DNAs from
      mycobacterial as well as non-mycobacterial organisms, grown from these specimens.
      It is recommended that for optimum sensitivity and specificity both EB staining
      and blot hybridization should be done.

PMID- 9030109
TI  - Pterygium in lepromatous leprosy.
AB  - Pterygia from the eyes of three lepromatous leprosy patients were
      histopathologically studied. All of the specimens contained acid-fast bacilli
      (AFB) and exhibited features of chronic inflammation. In the etio-pathogenesis of
      the pterygium that occurs in leprosy patients, the chronic inflammation that is a
      feature of the disease, the involvement of the nerves within the pterygium, the
      increased exposure to sunlight, dust and wind (especially in patients having
      lagophthalmos), and the ostrasization by society that necessitates living
      predominantly outdoor lives, should be taken into account.

PMID- 9030108
TI  - Enzyme-linked immunosorbent assay (ELISA) with mycobacterial crude antigens for
      the sero-epidemiological diagnosis of active tuberculosis.
AB  - In search for reliable, nonexpensive procedures for tuberculosis diagnosis
      suitable for seroepidemiological studies in leprosy-endemic areas, enzyme-linked
      immunosorbent assays (ELISAs) with whole intact bacilli, whole lipid-free bacilli
      and protein-enriched soluble extracts from the H37Rv Mycobacterium tuberculosis
      strain were evaluated. Sera tested came from 47 active, pulmonary tuberculosis
      adult cases, 60 household contacts of active tuberculosis cases, 20 lepromatous
      leprosy adult patients, and 67 healthy adult controls obtained from low and high
      leprosy and tuberculosis endemicity areas. There was no influence of such
      endemicity levels in the number of positive results in control sera. Antibody
      levels obtained with each of the antigens in ELISAs were significantly different
      in tuberculosis patients and the control groups. Ten percent of tuberculosis
      contacts were positive with some of the antigens and three of them showed
      suggestive chest radiographs. The best combination for a high number of positive
      results with tuberculosis sera and low positive results with leprosy sera was the
      BCG soluble extract (91% and 15%, respectively). This preparation also yielded
      excellent sensitivity and specificity values for tuberculosis (91.5% and 92.5%,
      respectively). These data suggest that BCG soluble extract ELISAs could provide
      helpful information to estimate tuberculosis prevalence only in leprosy-free
      areas, under a situation of unavailability of purified antigens. In pulmonary
      cases, sputum microscopic examination and culture have higher sensibility than
      serodiagnosis; therefore, the utilization of BCG soluble extract ELISAs as a
      diagnostic aid in individual patients with suspected active tuberculosis only can
      be useful in extrapulmonary cases.

PMID- 9030110
TI  - Electrophysiological evaluation of peripheral autonomic function in leprosy
      patients, leprosy contacts and controls.
AB  - Since there is immunocytochemical evidence that the initial damage in leprosy is
      directed at distal, small, unmyelinated nerve fibers, we investigated several
      electrophysiological methods for their potential value in detecting peripheral
      autonomic dysfunction in leprosy contacts and leprosy patients. Fingertip blood
      flow velocity and its control by vasomotor reflexes (VMR) with a laser Doppler
      flowmeter, fingertip skin temperature, and the sympathetic skin response (SSR) to
      exosomatic stimuli were studied in 89 leprosy patients, 36 leprosy contacts and
      47 normal subjects. Whereas there were no significant differences between the
      groups in fingertip skin temperature and resting blood flow velocity
      measurements, there were significant differences in the prevalence of impaired
      fingertip VMR and absent SSR. The prevalence of absent SSR in leprosy patients
      was 60.9%, in contacts 13.8%, in controls 6.3%. The prevalence of abnormal VMR in
      leprosy patients was 61.2%, in contacts 34.7% and in controls 10.6%. VMR testing
      is a more sensitive test method for autonomic dysfunction compared with the SSR.
      The implication of impairment in vasomotor and sudomotor function in leprosy
      contacts needs yet to be determined. However, we propose this to be a response to
      exposure to Mycobacterium leprae, which represents either ongoing nerve damage or
      nonprogressive residual autonomic nerve damage. We suggest that VMR testing and
      SSR are valuable methods to evaluate early leprous neuropathy.

PMID- 9030111
TI  - Leprosy in Hawaii; the end of an epidemic.
AB  - Two different patterns of leprosy have occurred in Hawaii. First is the
      continuing influx of infected people among immigrants from several leprosy
      endemic areas. The number of new cases among their descendents has tended to
      abate within one generation after arrival in Hawaii. The most recent example of
      this has occurred in Asians arriving since immigration laws were liberalized in
      1965, followed by a rise of imported leprosy, peaking in 1970-1980, then falling.
      The second pattern was an explosive epidemic among native Hawaiians, rising to
      its peak in the 1890s, then slowly subsiding, and now approaching zero. It
      appears that official disease-control efforts (physical isolation and/or early
      multidrug treatment) cannot fully explain the ending of the epidemic in Hawaii,
      in spite of the continuing importation of M. leprae. It is suggested that the
      influence of changing socioeconomic factors (nutrition, crowding, genetics) has
      been of importance, particularly among the Hawaiians, who have undergone profound
      foreign influence (both positive and negative) during the 150-year history of
      this epidemic. The late Dr. Ma Haide was responsible for leprosy control in
      China, where leprosy is also fading away, but not simultaneously in all
      subpopulations. He summarized his view by saying, "Leprosy lingers longest among
      the poorest" (personal communication). This statement appears to hold true for
      Hawaii, also.

PMID- 9030112
TI  - Regarding antileprosy vaccine--an apprehension by Dr. Prakash.

PMID- 9030113
TI  - M. leprae and macrophage secretory products modulate the expression of NgCAM on
      Schwann cell surface.

PMID- 9030114
TI  - Low rates of detection of mycobacterial secretory antigen 85 in sera of untreated
      leprosy patients.

PMID- 9030115
TI  - Prevalence of antibodies to hepatitis C among recently treated leprosy patients
      in Senegal parallels those in normal populations.

PMID- 9030116
TI  - Dormancy, drug resistance or dependency; some thoughts to ponder.

PMID- 9030117
TI  - Antileprosy drugs, pregnancy and fetal outcome.

PMID- 9030118
TI  - Recurrent erythema nodosum leprosum precipitated by antileprosy drugs.

PMID- 9030119
TI  - Needed research in chemotherapy of leprosy related to the individual patient.
AB  - The chemotherapy of leprosy was rendered markedly more effective by the
      introduction of WHO/MDT in 1981. The prospects for further improvements, both by
      shortening duration and by developing fully supervisable intermittent regimens,
      appear good at this time. These developments should aid the efforts to attain the
      goal of elimination of leprosy as a public health problem. For the foreseeable
      future, however, the goal of eradication of leprosy will continue to elude us.

PMID- 9030121
TI  - Bangkok Workshop on Leprosy Research. Research needs related to epidemiology and
      control: subclinical infection.

PMID- 9030120
TI  - Bangkok Workshop on Leprosy Research. Treatment of reactions and nerve damage.

PMID- 9030122
TI  - Bangkok Workshop on Leprosy Research. Predicting trends.

PMID- 9030123
TI  - Primary prevention of leprosy.

PMID- 9030124
TI  - Research priorities in leprosy: an operational perspective.

PMID- 9030125
TI  - Bangkok Workshop on Leprosy Research. Research needs related to disabilities and
      rehabilitation.

PMID- 9030126
TI  - Bangkok Workshop on Leprosy Research. Research needs of the post-elimination
      phase.

PMID- 9030127
TI  - Bangkok Workshop on Leprosy Research. Immunodiagnostics, including skin tests.

PMID- 9030128
TI  - The contribution of serological tests to leprosy control.

PMID- 9030129
TI  - Bangkok Workshop on Leprosy Research. Genome sequencing and its potential
      applications.

PMID- 9030130
TI  - The role of inflammatory cytokines in the tissue injury of leprosy.

PMID- 9030131
TI  - Immunoprophylaxis of leprosy--lessons from the TB program.

PMID- 9030132
TI  - Immunoprophylaxis against leprosy; the case for improved vaccines against
      leprosy.

PMID- 9030133
TI  - Chemotherapy of leprosy: progress since the Orlando Congress, and prospects for
      the future.

PMID- 9030134
TI  - Plastic surgeons: a gender comparison.
AB  - This study surveyed plastic surgeons for the purpose of identifying gender
      related differences within the specialty. A confidential 108-item questionnaire
      was mailed to all female members and candidates of the American Society of
      Plastic and Reconstructive Surgeons (ASPRS) and to an equal number of male
      colleagues. The survey was conducted between September of 1992 and October of
      1993 using a modified Dillman five-step computerized method. The response rate
      was 73 percent for women (157 of 216) and 57 percent for men (124 of 216). Of
      those who responded, 65 percent of women and 89 percent of men were married (p <
      0.01). Fifty-two percent of women and 86 percent of men had biologic children (p
      < 0.001). The majority of surgeons surveyed (97 percent) were in full-time
      surgical practice. Many women reported delaying childbearing until they had begun
      full-time practice of plastic surgery (p < 0.001). No significant gender-related
      differences were noted with respect to medical school rank, training history,
      advanced degrees, subspecialty practiced, hospital affiliation, or hours worked.
      Women surgeons in academic practice held lower rank than men and were less likely
      to be tenured (p < 0.04). Gross annual income was lower for women (p < 0.001). In
      contrast to men (27 percent), most women (89 percent) perceived sexual
      discrimination and harassment (p < 0.001). The majority of plastic surgeons were
      satisfied with their financial situation (80 percent), work (94 percent), and
      family life (76 percent). Over 90 percent of both women and men were happy with
      their career choice and would encourage medical students to become surgeons.
      Plastic surgeons do not differ in training or professional practice
      characteristics. Discrimination and harassment and unequal promotion and
      remuneration of women in the university environment are problems that need to be
      eliminated.

PMID- 9030135
TI  - Immunolocalization of transforming growth factor beta 1, beta 2, and beta 3 and
      insulin-like growth factor I in premature cranial suture fusion.
AB  - The etiology of craniosynostosis remains unknown. The beta group of transforming
      growth factors (TGF-beta) and insulin-like growth factors (IGF-I and IGF-II) are
      known to induce new bone formation and, when added exogenously, cause accelerated
      closure of calvarial defects. The possible roles of these bone growth factors in
      premature cranial suture fusion in humans have not been explored. We analyzed a
      total of 20 cranial suture biopsy samples (10 synostotic and 10 normal) from 10
      infants with single-suture craniosynostosis undergoing cranial vault remodeling.
      Using isoform-specific antibodies for TGF-beta 1, -beta 2, and -beta 3 and IGF-I,
      we demonstrated immunoreactivity of these growth factors were present in human
      cranial sutures; the TGF-beta 2 isoform was the most intensely immunoreactive.
      Most importantly, the TGF-beta isoforms and IGF-I showed more intense
      immunoreactivity in the actively fusing craniosynostotic sutures compared with
      the control patent sutures. Specifically, the TGF-beta isoforms and IGF-I were
      intensely localized in the osteoblasts synthesizing new bone at the suture
      margin. It is noteworthy that although the patent sutures were less
      immunoreactive for TGF-beta isoforms than fused sutures, there was a distinct
      pattern of the TGF-beta 3 isoform that was immunolocalized to the margin of the
      normal patent sutures. This suggests a possible role for TGF-beta 3 in
      maintaining cranial suture patency. The increased immunoreactivity of both TGF
      beta 2 and IGF-I in the actively fusing sutures compared with the patent control
      sutures indicates that these growth factors may play a role in the biology
      underlying premature suture closure. To our knowledge, this is the first study
      showing the presence of TGF-beta 1, -beta 2, and -beta 3 and IGF-I in prematurely
      fusing human cranial sutures. In the future, manipulating the local expression of
      these growth factors at the suture site may enable plastic surgeons to modulate
      premature suture fusion.

PMID- 9030136
TI  - Hypertelorism: nosologic analysis of 90 patients.
AB  - The word hypertelorism is used to describe increased interorbital distance, a
      condition that is causally and pathogenically heterogeneous. Because not all wide
      set eyes are the same, accurate terminology and nosology are critical to
      understanding and management. Orbital hypertelorism signifies an increased
      distance between both medial sides and lateral sides of the orbits. Interorbital
      hypertelorism denotes increased distance only between the inner orbital walls. In
      this retrospective analysis of 90 patients with hypertelorism, the most common
      cause was frontonasal malformation (n = 30), a heterogeneous category of
      nonfamilial disorders including a newly described subgroup, rugose frontonasal
      malformation. The second most common cause was craniofrontonasal dysplasia (n =
      18), a genetic syndrome comprising coronal synostosis, frontonasal anomalies,
      "frizzy" hair, narrow/sloping shoulder girdle deformity, and longitudinal ridging
      of nails in association with various truncal and extremity anomalies. Paramedian
      craniofacial cleft(s) (n = 10) and (sincipital) encephalocele (n = 6) were
      infrequent causes of hypertelorism. The fifth, miscellaneous category comprised
      well-defined, mostly chromosomal and syndromic disorders (n = 26). Patients in
      the various diagnostic categories were designated as having either orbital or
      interorbital hypertelorism. Hypertelorism also was graded as either first,
      second, or third degree based on deviation from age- and gender-matched normative
      data. The etiology and type of hypertelorism influence the selection of operative
      procedure, whereas the grade of severity indicates the need for surgical
      correction.

PMID- 9030137
TI  - Longitudinal analysis of mandibular asymmetry in hemifacial microsomia.
AB  - Reconstruction of the mandible is one of the key elements in the skeletal
      rehabilitation of patients with hemifacial microsomia. Unfortunately, knowledge
      about long-term mandibular skeletal growth in these patients is lacking. The
      purpose of this study was to analyze mandibular skeletal growth longitudinally in
      unoperated hemifacial microsomia patients from childhood to adolescence. The
      longitudinal records of 26 patients with unoperated unilateral hemifacial
      microsomia were utilized. The average age at initial records was 3.1 years, and
      the average age at final records was 16.7 years. Posteroanterior cephalometric
      radiographs were utilized to evaluate both horizontal and vertical mandibular
      asymmetry. Patients also were analyzed according to the grade and side of the
      mandibular deformity. A paired t-test (p < 0.05) and a two-way ANOVA were used to
      analyze the data. There were 5 patients with grade I, 14 with grade II, and 7
      with grade III. The results indicated that the skeletal mandibular asymmetry in
      hemifacial microsomia is not progressive in nature and that growth of the
      affected side in these patients parallels that of the nonaffected side. The grade
      and the side of the mandibular deformity did not influence these findings. These
      results should be considered when treatment strategies are developed to
      reconstruct the asymmetrical mandible in hemifacial microsomia.

PMID- 9030138
TI  - The transverse platysma myocutaneous flap for head and neck reconstruction.
AB  - This paper reports the platysma myocutaneous flap that has been modified to be
      directed transversely across the midportion of the neck, with its blood supply
      from the posterior cervical triangle. Seven flaps have been used to reconstruct
      wounds of the ear, cheek, and lips in six patients. One flap had a partial skin
      paddle loss when the flap was harvested from the neck of a patient who had had
      two previous surgical wounds to the neck and may represent an alteration of the
      blood supply secondary to surgical scarring. The remaining six flaps were robust,
      and all healed without complications.

PMID- 9030139
TI  - A simple method of reduction malarplasty.
AB  - The Oriental face is generally mesocephalic: short and wide. Thus the prominent
      zygoma in relation to a flat nose will make the face seem flatter. The
      unfavorable social connotations associated with a prominent zygoma are a reality
      in Korea. Reduction will not only relieve the patient of such psychological
      burdens but also afford a face with a cheerful and youthful appearance. Thus not
      a few patients seek surgery for these reasons. Previously, chiseling or burring
      of the zygoma body and arch was frequently used for zygoma reduction but was
      usually less than effective in reducing the wide face. Segmental osteotomy and
      repositioning of the arch by means of a bicoronal approach was another method,
      but this involved an extensive operation and left a long visible scar. We left
      that these methods were less than ideal as aesthetic procedures. A simple and yet
      effective method of reducing the prominent zygoma was needed. Reduction of the
      prominent zygoma was performed in 26 patients by shaving the zygoma body and
      displacing the zygomatic arch inwardly after two-point fracturing, greenstick
      fracture anteriorly, and complete osteotomy posteriorly by means of a small
      preauricular and upper buccal sulcus incision. We obtained satisfactory results
      using the relatively simple procedure. The advantages of our technique are as
      follows: (1) there is a small skin incision and resulting inconspicuous scar, (2)
      the technique is simple and effective, (3) there is no use of foreign bodies such
      as wires on miniplates, and (4) there is less postoperative discomfort.

PMID- 9030140
TI  - Reconstructed mandibular defects: fibula free flaps and osseointegrated implants.
AB  - Twenty patients with microvascular fibula flap reconstruction of oromandibular
      defects were selected for implant-retained prosthodontic rehabilitation. A total
      of 71 osseointegrated implants were placed within the grafted fibulas. Four
      patients had immediate implant placement at the time of their reconstructive
      surgery, and the remaining 16 patients had implants placed secondarily. One
      patient received postoperative radiation therapy (5910 cGy) 6 weeks following
      reconstruction and immediate implant placement. No implants were placed in
      previously irradiated flaps. A minimum 6-month period of osseointegration was
      allowed prior to second stage surgery. Fifty-four of the 71 implants were
      uncovered; 46 of these implants were functional, and 3 were in the process of
      being restored. Among the 54 implants (15 patients) that were uncovered, only 1
      failed to osseointegrate, 2 implants were reburied, and 2 were removed. The
      follow-up period ranged from 1 to 49 months since second stage surgery. Although
      a number of prosthodontic designs were used, 11 of the 15 patients were restored
      with removable overlay prostheses. Only those implants exposed to postoperative
      radiation demonstrated radiographic bone loss following functional loading.

PMID- 9030141
TI  - Histopathologic and biochemical changes in the muscles affected by distraction
      osteogenesis of the mandible.
AB  - Lengthening of the canine mandible using an intraoral distraction device was
      performed in order to study the effects of distraction on the associated muscles
      of mastication. Biopsies of the masseter and digastric muscles were taken after
      lengthening at four different time intervals to assess the temporal changes in
      the masticatory muscles of 10 dogs. Biopsies of the muscles on the contralateral
      side also were taken from 6 of these dogs before lengthening to establish a
      control group. Each biopsy was analyzed histologically and spectophotomerically
      for RNA, DNA and protein content. The digastric muscle underwent transient
      atrophy with initiation of distraction but regenerated completely after 48 days
      of fixation. The masseter muscle was unchanged initially but showed evidence of
      atrophy only after 20 mm of distraction it continued to exhibit evidence of
      atrophy during fixation. Protein synthesis was decreased significantly during
      periods of atrophy in the masseter; no such change was noted in the digastric.
      Unlike the masseter, the digastric fibers lie in a plane parallel to the vector
      of distraction. These findings suggest that any muscle affected by skeletal
      distraction in the same plane or vector (e.g., digastric) adapts with
      compensatory regeneration and hypertrophy. Moreover, those muscles lying in a
      different plane (e.g., masseter) show persistent evidence of atrophy with
      decreased protein synthesis.

PMID- 9030142
TI  - Durability of prefabricated versus normal random flaps against a bacterial
      challenge.
AB  - Numerous reports of flap prefabrication have demonstrated good survival. The
      durability of these flaps compared with that of other flap types or normal
      tissue, however, remains unknown. The purpose of this study was to determine how
      prefabricated flaps respond to a bacterial challenge compared with identically
      sized normal random-pattern flaps. Rat abdominal cutaneous-panniculus carnosus
      flaps were prefabricated with a standard-sized groin fasciovascular tissue
      carrier and then inoculated with Staphylococcus aureus. The prefabricated flaps
      were divided into two groups. Group one (standard prefabricated flap, n = 24)
      received no growth factor. Group two (n = 24) received an angiogenic growth
      factor between the carrier and flap tissue. A random-pattern flap served as a
      nonprefabricated control (n = 12). Grading of the prefabricated flaps with growth
      factor versus the standard prefabricated flaps versus controls showed dehiscence
      (41 versus 37 versus 4 percent), ulceration (21 versus 29 versus 18 percent),
      erythema/cellulitis (40 versus 44 versus 8 percent), and necrosis (9 versus 29
      versus 0 percent). The control flaps had significantly less dehiscence, erythema/
      cellulitis, and necrosis than the standard prefabricated flaps. Similarly, the
      prefabricated flaps with angiogenic growth factor had significantly less necrosis
      than the standard prefabricated flaps. CONCLUSIONS: (1) prefabricated flaps were
      demonstrated to be less durable than random-pattern flaps against a bacterial
      challenge, (2) angiogenic growth factor may help to improve the durability of
      prefabricated flaps against bacterial infection, and (3) the biologic behavior of
      prefabricated flaps is not the same as that of normal tissue and deserves further
      investigation.

PMID- 9030143
TI  - Clinical applications and technical limitations of prefabricated flaps.
AB  - Vascular pedicle implantation into the subdermal level of the skin induces an
      angiogenic response that can be sufficient to artificially create or
      "prefabricate" an axial-pattern flap suitable for island pedicle or free-flap
      transfer. This technique allows the creation of large, thin skin flaps that
      retain the qualities of the donor-site skin. Three cases are presented in which
      such thin flaps have been created to cover defects, one on the knee and two on
      the face. While the reconstructions are satisfactory, difficulties were
      encountered with venous insufficiency in the flaps after the second-stage
      transfer. We believe that the complexity and staged nature of these procedures
      limit their application to highly selected patients, but their role probably lies
      in the transfer of supraclavicular skin for the reconstruction of facial defects.

PMID- 9030144
TI  - Evaluation of fat in breast tissue removed by vertical mammaplasty.
AB  - Breast liposuction, performed immediately prior to surgical reduction, has proven
      to be an efficient adjuvant method to reduce large breasts, even in young
      patients. Experience has shown, however, that liposuction is difficult or
      impossible in breasts in which fat is intimately mixed with glandular tissue.
      Clinical examination gives no information about the breast content. In order to
      evaluate the fat content of the breast, 33 unselected specimens removed during
      breast reductions (20 with liposuction and 13 without liposuction) were subjected
      to melting in a microwave oven. The fat separated from the residue could be
      weighed. This confirmed that pure glandular breasts are uncommon and that breast
      fat varies largely from one patient to another, with extremes of 2 and 78 percent
      and a mean value of 48 percent. Breast fat increases with age, with the body
      mass, and with the total volume of the breast. Clinical implications of these new
      data deserve investigation.

PMID- 9030146
TI  - The spontaneous return of sensibility in breasts reconstructed with autologous
      tissues.
AB  - Some spontaneous return of sensibility following autologous tissue breast
      reconstruction is often suspected but not well documented. In the present study,
      objective touch-pressure, pain, temperature, and vibratory sensibilities were
      recorded in 33 autologous breast reconstructions at an average of 25.2 months
      postoperatively. Correlation of the sensory return with patients' satisfaction
      toward reconstruction was done by a detailed questionnaire. All except one
      patient regained a variety of sensibilities touch pressure in 97 percent of
      patients (averaging 81.05 gm/mm2 versus control of 7.98 gm/mm2), pain in 88
      percent of patients, heat in 64 percent of patients (45 percent of quadrants),
      cold in 82 percent of patients (67 percent of quadrants), and high- and low
      frequency vibration in 100 percent of patients (high in 90 percent of quadrants,
      low in 96 percent). Subjectively, 94 percent considered their chest comfortable
      to touch following reconstruction compared with 34 percent following mastectomy.
      On a scale from 1 to 10, patients rated their reconstructions an average of 9.3.
      Our findings confirm the spontaneous return of sensibility following a variety of
      autologous tissue breast reconstructions. The value of the sensory return is
      suggested by the high degree of satisfaction in nearly all patients. Further
      attempts to correlate the degree of sensory return with the degree of
      satisfaction were inconclusive because of the uniformly high satisfaction
      reported by the patients. The mechanism of reinnervation appears to come both
      from the skin margins and from the deep surface of the flap. Future developments
      in breast reconstruction should take into consideration the eventual quality of
      sensory return.

PMID- 9030147
TI  - An anatomic study of the internal mammary veins: clinical implications for free
      tissue-transfer breast reconstruction.
AB  - The anatomy of the internal mammary vessels is poorly understood and thought to
      be unreliable clinically for use as a recipient vein in free-tissue-transfer
      breast reconstruction. This study of 10 fresh cadaver thoracic cavities
      demonstrated by anatomic and dye resection studies that the internal mammary
      veins become smaller (< or = 2 mm) distally (fourth rib) and bifurcate [left (90
      percent) > right (40 percent)], becoming unsuitable for consistent venous
      anastomoses at or below the fourth interspace. Furthermore, this study suggests
      that the most consistent interval is the third rib, which offers an appropriate
      recipient vein (40 percent > or = 3 mm on the left and 70 percent > or = 3 mm on
      the right). However, at the fourth interspace, 20 percent of the cadaver
      specimens had a vein on one side that was 1 mm or less and therefore unsuitable
      as a recipient. This enhanced understanding of the anatomy (size, location, and
      consistency) of the internal mammary recipient veins offers our patients another
      recipient option to enhance the safety and technical ease of microvascular breast
      reconstruction.

PMID- 9030148
TI  - Recipient vessels in free-flap breast reconstruction: a study of the internal
      mammary and thoracodorsal vessels.
AB  - The internal mammary vessels as recipient site for free flaps in breast
      reconstruction were investigated in this paper because of their ideal location
      for breast reconstruction. Comparisons were made with the thoracodorsal vessels
      in terms of external vessel diameter, vessel size discrepancy, flap loss and
      reexploration rates, and ease of flap placement. Eighty-one patients underwent
      110 breast free-flap reconstructions (92 TRAM flaps and 18 superior gluteal
      flaps) between 1988 and 1994. Vessel size measurements were available on 75
      flaps. The internal mammary artery diameter (2.36 +/- 0.50 mm, n = 51) was
      significantly larger than the thoracodorsal artery diameter (1.79 +/- 0.34 mm, n
      = 23; p < 0.001). There was no significant difference between the diameters of
      the internal mammary vein 2.6 +/- 0.58 mm, n = 52) and thoracodorsal vein (2.51
      +/- 0.50 mm, n = 23; p = 0.93). The right internal mammary artery (2.52 +/- 0.51
      mm) was significantly larger than the left internal mammary artery (2.30 +/- 0.55
      mm; p = 0.046). The right internal mammary vein (2.89 +/- 0.56 mm) also was
      significantly larger than the left internal mammary vein (2.31 +/- 0.48 mm; p =
      0.002). In terms of vessel size discrepancy, the internal mammary recipient
      artery tended to be greater in size than the TRAM flap donor artery (p = 0.003),
      while the thoracodorsal recipient artery tended to be smaller than the TRAM flap
      donor artery (p = 0.002). Flap failures and flap reexplorations occurred in the
      group using the thoracodorsal vessels but not in the internal mammary group.
      Correct flap placement using the internal mammary recipient site was achieved
      more easily for both unilateral and bilateral reconstructions because of the
      avoidance of lateral fullness and medial deficiency problems. The internal
      mammary recipient site is an important and at times superior alternative to the
      axillary recipient site because of its larger artery, especially when the axilla
      is scarred. For smaller free flaps such as a hemi-TRAM flap, as in bilateral TRAM
      flap reconstructions, the internal mammary site is invaluable because this
      recipient site allows exact placement of a smaller flap in the breast area.

PMID- 9030149
TI  - Abdominal-wall recovery following TRAM flap: a functional outcome study.
AB  - Abdominal-wall function was evaluated preoperatively and at intervals
      postoperatively in 25 consecutive patients undergoing breast reconstruction with
      transverse rectus abdominis myocutaneous (TRAM) flaps (single-pedicled TRAM flap,
      14 patients; free TRAM flap, 9 patients; and bilateral free TRAM flaps, 2
      patients). Objective measures of abdominal-wall function were performed with the
      B200 Isostation, a triaxial dynamometer. In addition, the patients were assessed
      by a physical therapist and filled out an activity questionnaire at each
      postoperative examination. Tests of abdominal-wall function demonstrated the
      greatest decrease in performance at the 6-week postoperative tests of flexion.
      The maximum isometric flexion torque of the pedicled TRAM flap group decreased to
      58 +/- 10 percent, while the unilateral free TRAM flap group average was 87 +/-
      11 percent of baseline. For the pedicled TRAM flap group this difference was
      significant (p = 0.004). By the 6-month evaluation, the maximum isometric flexion
      torque increased for both the pedicled and the free TRAM flap groups to 89 +/- 13
      percent and 93 +/- 8 percent of baseline, respectively. The physical therapist
      evaluation of abdominal-wall strength and the activity questionnaire data showed
      no statistically significant differences between groups or over time. Rectus
      abdominis muscle harvest for pedicled TRAM flaps causes a greater insult to the
      abdominal wall than does free TRAM flap harvest. The ultimate clinical effect of
      the sacrifice of even an entire rectus abdominis muscle appears to be well
      tolerated by most patients. This is the first prospective outcome study of
      abdominal-wall function in TRAM flap patients. The clinical implications of this
      information will be discussed.

PMID- 9030150
TI  - Reconstruction of breast asymmetry in Poland's chest-wall deformity using
      microvascular free flaps.
AB  - Poland's syndrome comprises a spectrum of chest-wall deformities affecting, to
      various degrees, the rib cage, the chest-wall muscles, the neurovascular
      structures of the ipsilateral arm, and the overlying breast. This study details
      our experience with nine female Poland's syndrome patients who had chest-wall and
      breast asymmetry corrected by microvascular free-tissue transfer. Nine female
      patients with Poland's chest deformity underwent 12 microvascular free flaps
      between 1989 and 1994. Donor sites for free-tissue transfer included eight
      transverse rectus abdominis flaps, two superior gluteal flaps, one inferior
      gluteal flap, and one contralateral latissimus dorsi flap. Recipient vessels were
      branches of the subscapular vascular axis in all patients. Patients' ages ranged
      from 18 to 47 years at the time of reconstruction. Chest-wall and breast
      asymmetry varied from accompanying severe pectus and rib cage deformities to
      isolated breast involvement. Complications were limited to a superior gluteal
      flap loss due to anomalous subscapular venous drainage. This patient underwent a
      successful second superior gluteal flap reconstruction utilizing the cephalic
      venous outflow system. Chest-wall and breast symmetry was restored in all
      patients. This study demonstrates that microsurgical reconstruction of chest-wall
      and breast asymmetry in Poland's syndrome yields excellent results with a high
      degree of patient satisfaction. Careful intraoperative assessment of the
      recipient vessels prior to flap transfer is mandatory. Because Poland's chest
      wall deformity may include anomalies of the vascular system, preoperative
      vascular assessment with duplex ultrasonography should be considered in all
      patients, and use of preoperative angiography or venography in selected patients
      also appears justified.

PMID- 9030151
TI  - Flap closure of postpneumonectomy empyema.
AB  - Empyema continues to be an uncommon, frustrating, and potentially lethal
      complication of pneumonectomy. Between 1990 and 1994 we treated 16 cases of
      recalcitrant postpneumonectomy (partial or total) empyema with combinations of
      pulse lavage, sharp debridement, muscle flaps, myodermal flaps, and
      thoracoplasty. We performed 11 pectoralis muscle flaps, 6 serratus anterior
      muscle flaps, 9 latissimus dorsi muscle flaps, 6 rectus abdominis muscle flaps,
      and 1 trapezius muscle flap for an average of 2.1 muscle flaps per patient. There
      was 1 omental flap. Of these flaps, 2 were free and the rest pedicled. Ten of the
      muscle flaps carried deepithelialized cutaneous paddles, and 6 were larger than
      150 cm3. Thoracoplasty was done in 11 patients to decrease the volume of the
      postpneumonectomy empyema cavity. Of 16 patients, 4 failed initially because of
      persistent bronchopleural fistula or infection but resolved after one additional
      procedure. There was 1 perioperative death, 3 reoperations for bleeding, 1
      patient with upper extremity deep vein thromboses, 1 seroma, and 1 patient with
      significant postoperative pain syndrome. In order to determine the efficacy of
      different operative approaches, patients were retrospectively divided into two
      groups according to the number of operations using flaps needed to resolve their
      postpneumonectomy empyema. Group A required only one operation using flaps to
      eliminate the postpneumonectomy empyema. Group B required two operations using
      flaps to remedy the postpneumonectomy empyema. Group B operations were further
      classified into B1, for the first operation, and B2, for the second operation. No
      patient needed more than two operations using flaps. Three significant variables
      were identified, the number of muscle flaps, the number of ribs in any
      thoracoplasty, and the preoperative serum albumin level. The A and B2 groups had
      significantly more muscle flaps transposed (p = 0.006) and ribs resected (p =
      0.0002) than the B1 group. These findings suggest that filling the
      postpneumonectomy empyema space with muscle and collapsing any remaining space by
      thoracoplasty were the most successful strategy. The B2 group's average albumin
      level was significantly higher (p = 0.03) than that in either the A or the B1
      group, suggesting that improved nutrition may have played a role in the lack of
      recurrence. Our goals of single-stage closure and decontamination of empyema
      cavities were best achieved by following these principles: removal of infected
      and necrotic tissue using sharp debridement and pulsed lavage, repair of
      bronchopleural fistulas with muscle flaps, and minimization of the dead space
      with combinations of muscle flaps and thoracoplasty.

PMID- 9030152
TI  - Hair as a filler material for reconstructive or cosmetic surgery.
AB  - The purpose of this study was to investigate the possible use of hair as a filler
      material for reconstructive or cosmetic surgery. Many implant materials tested so
      far have proved to be of limited usefulness due to a lack of staying power or to
      fears of a host immune response, among other problems. In this study, pellets of
      rat hair were placed subcutaneously or beneath the pectoral muscle of Lewis rats
      (10 rats per group). A thin vascularized fibrous pouch containing inflammatory
      cells had formed around the hair pellet at 4 months. By 8 to 12 months, the hair
      had compacted, and the fibrous matrix of the pouch showed very few inflammatory
      cells surrounding the embedded hairs. There was no evidence of implant rejection,
      granuloma formation, or hair degradation up to 12 months after implantation. The
      results indicate that hair merits further study as a surgical implant material.

PMID- 9030153
TI  - Heel reconstruction.
AB  - From 1987 through 1990 we used the compound flap formed by the lateral leg flap,
      the fibula, and its surrounding soft tissues, pedicled on the distal peroneal
      vessels, to reconstruct heel and calcaneus defect in two patients. Both were
      successful and functionally good.

PMID- 9030154
TI  - The lateral arm fascial free flap for resurfacing of the hand and fingers.
AB  - The lateral arm free flap can be harvested as a fascial flap or fasciocutaneous
      flap. In this report we describe the use of the lateral arm fascial flap for
      degloving injuries of the fingers and for skin loss on the dorsum of the hand
      with exposure of tendons and bones. Concomitant reconstruction of a missing
      phalanx with a portion of the distal humerus is also described. The use of the
      fascial flap allows a large area of tissue to be harvested, and still, the donor
      site can be closed primarily. The fascia is thin and pliable and so conforms well
      to the contour of the fingers. Its bulk does not interfere with finger motion,
      and its undersurface creates a gliding surface for tendons. Complications in the
      reported cases were negligible.

PMID- 9030155
TI  - The lateral forearm flap: an anatomic study.
AB  - The anatomy of the lateral forearm flap has been studied in 12 fresh cadaver arms
      with methylene blue and latex injections and arteriography. The posterior radial
      collateral artery was found to divide constantly into two terminal branches, an
      anterior and a posterior division. The anterior division is the nutrient vessel
      of the flap. This artery extends significantly beyond the lateral epicondyle of
      the elbow into the lateral aspect of the forearm (range 13 to 18 cm, average 15
      cm). This allows raising a fasciocutaneous flap in the proximal forearm with a
      much longer vascular pedicle than the classic lateral arm flap. Other advantages
      include very thin skin and subcutaneous tissue and less sensory deficit at the
      donor site. Based on these results, this newly designed lateral forearm flap has
      been used in 13 clinical cases. Its main indications are whenever soft, thin,
      pliable skin is needed for small to moderate-sized defects.

PMID- 9030156
TI  - Single exposures to 5-fluorouracil: a possible mode of targeted therapy to reduce
      contractile scarring in the injured tendon.
AB  - After injury, adhesions may develop between the digital flexor tendons and their
      sheaths. Fibroblasts are key cells in this fibrotic adhesive process, and two
      possible sources for these cells are the synovial sheath and the endotenon tissue
      (tendon core). Fibroblasts seeded into a collagen lattice will contract the
      collagen. This fibroblast-populated collagen lattice contraction was used to
      investigate the ability of the fibroblasts from the synovial sheath and endotenon
      to reorganize collagen (an important function in the formation of adhesions).
      Endotenon and synovial fibroblasts isolated from 30 animals were used in the
      study. Synovial fibroblasts produced significantly greater collagen lattice
      contraction compared with endotenon fibroblasts (p < 0.05). The possibility of
      preventing collagen lattice contraction with a single, nontoxic 5-minute
      treatment of the fibroblast-populated collagen lattices with the antimetabolite 5
      fluorouracil was investigated. Compared with controls the degree of fibroblast
      populated collagen lattice contraction was significantly inhibited (p < 0.05)
      with the use of 5-fluorouracil for endotenon and synovial cells. These results
      demonstrate the potential for locally targeted therapy in tendon healing. Because
      of the different contractile properties of the two cell lines, a change in the
      balance between intrinsic and extrinsic healing might be achieved with this
      method of therapy; in turn, this might lead to better functional results
      following surgery.

PMID- 9030157
TI  - Cell adhesion and short-term patency in human endothelium preseeded 1.5-mm
      polytetrafluoroethylene vascular grafts: an experimental study.
AB  - It has been shown that endothelialization improves short-term patency of 1.5-mm
      expanded polytetrafluoroethylene vascular grafts. A model for endothelialization
      of 1.5-mm expanded polytetrafluoroethylene vascular grafts with human endothelial
      cells is described. In this model, the adherence of endothelial cells was
      increased significantly in grafts coated with serum proteins and collagen. By
      means of this protocol, graft patency was tested after implantation in two animal
      models: the rat aorta and the rabbit common carotid artery. Anastomosis was
      performed with a 3M Precise Microvascular Anastomotic System. In both animal
      models, no significant loss of endothelial cells in the precoated grafts (rat, n
      = 8) were noted 1 hour after blood flow restoration. All uncoated grafts showed
      significant endothelial cell loss. In the rabbit model, all nonendothelialized
      grafts (n = 8) clotted 5 to 25 minutes after flow restoration. Seven (n = 8)
      endothelialized grafts showed no clotting during 1 hour's observation: one
      clotted immediately for a patency rate of 87.5 percent. These results indicate
      that endothelialization of 1.5-mm grafts is practical. Furthermore, adhesion of
      endothelial cells to the graft walls is not affected by short-term, pulsatile,
      high-pressure blood flow.

PMID- 9030158
TI  - Dynaflex prosthesis in total phalloplasty.
AB  - Because of the high rate of complications and because voiding while standing is a
      priority for most female-to-male transsexuals, until recently, I have refrained
      from implantation of a rigidity prosthesis in total phalloplasty. However,
      promising results have been obtained with self-contained Dynaflex hydraulic
      penile implants. The results and complications observed in my first five cases
      are reported in order to help prevent failure in future cases. I advocate
      implantation as a secondary procedure after the neophallus has gained
      sensitivity. The penile prosthesis should be covered by a Dacron prosthesis to
      ensure optimal encapsulation and collagen ingrowth. Since the neophallus girth
      will not allow for two prostheses to be implanted, and because properly
      serviceable crus penis is lacking in female-to-male transsexuals, I further
      advocate fixation of the one cylinder to the pubic symphysis. For insertion, the
      neoscrotal approach is superior. I maintain that combination of a neourethra and
      a rigidity prosthesis in one neophallus remains a challenge, both to the patient
      and to the surgeon.

PMID- 9030159
TI  - Midgestational sciatic nerve transection in fetal sheep results in absent nerve
      regeneration and neurogenic muscle atrophy.
AB  - In order to test whether fetal nerve healing and regeneration result in complete
      functional recovery, we transected the sciatic nerve at trunk level in 13
      midgestational sheep fetuses. In 10 fetuses immediate microsurgical nerve
      coaptation was performed. The neonatal lambs were evaluated clinically,
      electrophysiologically, and histologically. On the transected side, the 10
      surviving lambs showed a sensorimotor sciatic nerve paralysis and atrophy of the
      muscles innervated by the sciatic nerve. Somatosensory evoked potentials were
      weakly present in 5 animals and absent in 5 animals. Histologically, minimal
      signs of axonal regeneration, massive degeneration of the entire nerve, and a
      marked neurogenic muscle atrophy were found. These unexpected results differ from
      the findings after peripheral nerve transections in late gestational sheep
      fetuses and also from the classic wallerian degeneration-regeneration pattern
      that follows adult nerve injury. We speculate that the almost absent regenerative
      potential at midgestation is related to axotomy-induced neurotrophic factor
      deprivation during a developmental phase where the neurons are critically
      dependent on growth factor for survival.

PMID- 9030160
TI  - Postoperative blood flow monitoring after free-tissue transfer by means of the
      hydrogen clearance technique.
AB  - The hydrogen clearance technique was introduced for monitoring postoperative
      blood flow after free-tissue transfer in this prospective clinical study. This
      technique allows unlimited repeatable quantitative measurements of tissue blood
      flow in milliliters per minute per 100 gm of tissue at any site including buried
      flaps. In this study a real-time blood flow measuring system (Ameflow, Ameda,
      Switzerland) was employed. Two thousand eight hundred and twenty-three blood flow
      measurements were carried out on 72 free-tissue transfers, which were performed
      on 71 patients. Nine of these 72 flaps showed vascular complications (12.5
      percent), including arterial thrombosis in 6.9 percent (n = 5), hematoma in 4.2
      percent (n = 3), and venous thrombosis in 1.4 percent (n = 1). Complications as
      well as uneventful postoperative cases were monitored correctly by the hydrogen
      clearance technique in all cases, reaching sensitivity and specificity values of
      1.0 for this technique in our study. Furthermore, all complications could be
      detected earlier by the hydrogen clearance technique than by clinical monitoring
      alone, which allowed flap salvation in 7 of 9 cases and a resulting permanent
      failure rate of free-tissue transfer of 2.8 percent (n = 2). From our data we
      conclude that the hydrogen clearance technique is a promising tool for
      postoperative blood flow monitoring after free-tissue transfer. For experimental
      pathophysiologic and pharmacologic studies of tissue blood flow in flaps, further
      evaluation of our measuring device including comparative studies with other
      established techniques is highly recommended.

PMID- 9030161
TI  - Reconstruction following total laryngopharyngoesophagectomy and extensive
      resection of the superior mediastinum.
AB  - Our experience with four patients who underwent immediate reconstruction
      following total laryngopharyngoesophagectomy and extensive resection of the
      superior mediastinum is presented. The reconstructive procedures included free
      jejunal graft or microvascularly augmented gastric pedicle for esophageal
      reconstruction, pectoral fasciocutaneous or myocutaneous flap for tracheal
      reconstruction, and mesenteric flap connected with jejunal graft omental flap, or
      pectoral flap for protection of the great vessels and obliteration of the dead
      space in the cervical and superior mediastinal region. The reconstructive
      procedures were successful, and no pharyngocutaneous fistula, mediastinitis, or
      great vessel rupture was noted in any patient. There was one patient who
      developed lung edema and liver dysfunction postoperatively. Combinations of
      reconstructive procedures using well-vascularized soft tissues can be expected to
      provide well-tolerated reconstruction following extensive cervical and superior
      mediastinal resection.

PMID- 9030162
TI  - The role of subcutaneous infiltration in suction-assisted lipoplasty: a review.

PMID- 9030163
TI  - Total traumatic amputation of the lower face and upper half of the neck.

PMID- 9030164
TI  - Total external and internal construction in arhinia.
AB  - This case report relates to the surgical treatment of arhinia in a 6-year-old
      child. The external nose was constructed during the first stage with a forehead
      flap and a triangular rib graft. The nasal cavities were drilled out and lined
      during the second stage. In a third stage, the cavities were amplified, and
      silicone tubes were introduced for at least 1 year.

PMID- 9030165
TI  - Arterialized occipitoparietal osteocutaneous flap.
AB  - We treated a case of postoperative osteomyelitis and epidural abscess in the left
      temporal and parietal region. The scalp and skull defect following debridement
      was reconstructed immediately with an arterialized occipitoparietal
      osteocutaneous flap that was supplied proximally by the occipital artery and
      distally by the superficial temporal artery. This method is one of the
      alternative methods for small to moderately sized skull and scalp defects in the
      temporal, parietal, and occipital areas without available superficial temporal
      artery.

PMID- 9030166
TI  - Two cases of Merkel cell carcinoma cured by intratumor injection of natural human
      tumor necrosis factor.
AB  - Two patients were treated with intratumor injection of natural human tumor
      necrosis factor for recurrent or primary Merkel cell carcinoma. In both patients,
      local chemotherapy achieved complete tumor regression without causing ulceration
      or scarring. These results suggest that intratumor injection of natural human
      tumor necrosis factor may be very effective for the treatment of Merkel cell
      carcinoma.

PMID- 9030167
TI  - Application of the extended superficial musculoaponeurotic system flap to facial
      clefts.
AB  - We believe that the extended SMAS technique may be useful in selected facial
      cleft patients. In three Treacher Collins patients, this technique produced a
      modest improvement in the quantity and quality of the malar soft tissue that had
      not been achieved after orbitozygomatic or maxillomandibular surgery.

PMID- 9030168
TI  - How to use a gel template for an exact facial flap transfer.
AB  - A variety of materials have been used as template materials to aid in the design
      of local facial flaps. The biggest criticism of these materials is that they do
      not conform sufficiently to complex defects. This report describes the use of a
      hydrogel sheet wound dressing (ClearSite, NDM, Akron, Ohio) as a template
      material. ClearSite appears to make an ideal template material because it is
      thin, pliable, transparent, and inexpensive. This gel template adequately
      conforms to irregular three-dimensional shapes. It has the added beneficial
      ability to "lift" marking pen lines, which can then be transferred as an exact
      replica of the defect size. A case is presented in which a ClearSite template
      directed the transfer of the exact amount of forehead tissue following excision
      of a complex congenital nevus of the nose. Use of the ClearSite template seems
      well suited to help in local facial flaps and is likely to simplify the design of
      many distant flaps as well.

PMID- 9030169
TI  - Total lower lip reconstruction with a sensate composite radial forearm-palmaris
      longus free flap and a tongue flap.
AB  - The technique of total lower lip reconstruction with a composite radial forearm
      palmaris longus free flap was further refined in this report. A ventral tongue
      flap enhanced the lip aesthetics by recreating the vermilion. Lip suspension was
      enhanced by securing the palmaris tendon to the malar eminences as well as to the
      cut ends of the orbicularis oris muscle. The patient achieved oral continence as
      well as dynamic movement of the lip during speaking and swallowing.

PMID- 9030170
TI  - Personal approach to treatment of prominent ears.
AB  - A description is presented of an anterior approach to the treatment of prominent
      ears with Kaye's method but with a few modifications to simplify it. Confirmation
      of the method's advantages is discussed.

PMID- 9030171
TI  - A reversed-flow latissimus dorsi musculocutaneous flap based on the serratus
      branch in primary shoulder reconstruction.
AB  - We report a case using the latissimus dorsi musculocutaneous flap based on the
      serratus branch in primary shoulder reconstruction. The reversed flow of the
      serratus branch maintained the circulation of the flap following acute disruption
      of the thoracodorsal vessels. Although our case was unusual, the reversed-flow
      latissimus dorsi flap based on its serratus branch may add a useful option in
      some cases.

PMID- 9030172
TI  - Leonardo Fioravanti (1517-1588): a barber-surgeon who influenced the development
      of reconstructive surgery.
AB  - Surgery in the Middle Ages was practiced by individuals belonging to the guild of
      barbers, with no basic medical education. The transformation into a scientific
      branch of medicine began in the sixteenth century. In this process, a great role
      was the one played by Leonardo Fioravanti. He was a Doctor in Medicine graduated
      from the University of Bologna. A controversial man, he was also an innovation in
      many fields of medicine, such as prevention of diseases, pharmacology, therapy,
      etc., and he was a surgeon himself. On the way back from one of the last
      Crusades, he visited the Vianeos brothers in Calabria, and he was able to learn
      from them the technique for reconstructing the nose that had been devised by
      Antonio Branca in the previous century and still practiced only by barber
      surgeons. He published his experience in a book that probably inspired the
      contemporary, Gaspare Tagliacozzi, Professor at the University of Bologna, and
      allowed him to become acquainted with this kind of reconstructive surgery.
      Tagliacozzi understood the value of the method described by Fioravanti and
      transformed a barber-surgery technique into a remarkable chapter of scientific
      surgery by divulging in the academic circles the principles of the pedicled flap,
      which have been the basis for development of modern plastic surgery.

PMID- 9030173
TI  - The origin of the Plastic Surgery Program at Columbia-Presbyterian Medical
      Center.

PMID- 9030174
TI  - A proximal interphalangeal joint fracture-dislocation treated by limited open
      (percutaneous) reduction and dynamic external fixation.

PMID- 9030175
TI  - Skin grafting on liver.

PMID- 9030176
TI  - The nonmist motor.

PMID- 9030177
TI  - Keeping spectacle-mounted loupes on comfortably.

PMID- 9030178
TI  - Comparison of rigid plate versus wire fixation in the management of zygoma
      fractures: a long-term follow-up clinical study.

PMID- 9030179
TI  - Vaginal depth following reconstruction with pudendal thigh flaps in congenital
      vaginal atresia.

PMID- 9030180
TI  - Where's the point?

PMID- 9030181
TI  - Notes on the history of the adoption of liposuction.

PMID- 9030182
TI  - Transient axillary-upper inner arm subcutaneous fibrous banding.

PMID- 9030183
TI  - Suppression of cleft lip and/or palate formation with transplantation of
      fertilized ovum.

PMID- 9030184
TI  - Optimal dose of cyclosporine for experimental rat.

PMID- 9030185
TI  - What is adequate fill? Implications in breast implant surgery.

PMID- 9030186
TI  - Reston: an alternate method of skin graft fixation.

PMID- 9030187
TI  - Under-running sutures for easy stitch removal.

PMID- 9030188
TI  - Cloning and characterization of a cotton lipid transfer protein gene specifically
      expressed in fiber cells.
AB  - A cotton genomic library was screened using a fiber-specific cDNA (GH3) encoding
      a lipid transfer protein (LTP). One genomic clone (1.7 kb DNA insert) containing
      the Ltp gene (Ltp6) was sequenced and characterized. The Ltp6 contains an open
      reading frame of 360 bp, which is interrupted by a single intron (136 bp) located
      in the region corresponding to the C-terminal of the protein. The derived amino
      acid sequence of LTP6 is 64% homologous to that of GH3. Like the GH3 gene, the
      Ltp6 is specifically expressed in fiber cells in a temporal manner. However, its
      expression level is lower than that of GH3.

PMID- 9030189
TI  - Thia fatty acids, metabolism and metabolic effects.
AB  - (1) The chemical properties of thia fatty acids are similar to normal fatty
      acids, but their metabolism (see below: points 2-6) and metabolic effects (see
      below: points 7-15) differ greatly from these and are dependent upon the position
      of the sulfur atom. (2) Long-chain thia fatty acids and alkylthioacrylic acids
      are activated to their CoA esters in endoplasmatic reticulum. (3) 3-Thia fatty
      acids cannot be beta-oxidized. They are metabolized by extramitochondrial omega
      oxidation and sulfur oxidation in the endoplasmatic reticulum followed by
      peroxisomal beta-oxidation to short sulfoxy dicarboxylic acids. (4) 4-Thia fatty
      acids are beta-oxidized mainly in mitochondria to alkylthioacryloyl-CoA esters
      which accumulate and are slowly converted to 2-hydroxy-4-thia acyl-CoA which
      splits spontaneously to an alkylthiol and malonic acid semialdehyde-CoA ester.
      The latter presumably is hydrolyzed and metabolized to acetyl-CoA and CO2. (5)
      Both 3- and 4-thiastearic acid are desaturated to the corresponding thia oleic
      acids. (6) Long-chain 3- and 4-thia fatty acids are incorporated into
      phospholipids in vivo, particularly in heart, and in hepatocytes and other cells
      in culture. (7) Long-chain 3-thia fatty acids change the fatty acid composition
      of the phospholipids: in heart, the content of n-3 fatty acids increases and n-6
      fatty acids decreases. (8) 3-Thia fatty acids increase fatty acid oxidation in
      liver through inhibition of malonyl-CoA synthesis, activation of CPT I, and
      induction of CPT-II and enzymes of peroxisomal beta-oxidation. Activation of
      fatty acid oxidation is the key to the hypolipidemic effect of 3-thia fatty
      acids. Also other lipid metabolizing enzymes are induced. (9) Fatty acid- and
      cholesterol synthesis is inhibited in hepatocytes. (10) The nuclear receptors
      PPAR alpha and RXR alpha are induced by 3-thia fatty acids. (11) The induction of
      enzymes and of PPAR alpha and RXR alpha are increased by dexamethasone and
      counteracted by insulin. (12) 4-Thia fatty acids inhibit fatty acid oxidation and
      induce fatty liver in vivo. The inhibition presumably is explained by
      accumulation of alkylthioacryloyl-CoA in the mitochondria. This metabolite is a
      strong inhibitor of CPT-II. (13) Alkylthioacrylic acids inhibits both fatty acid
      oxidation and esterification. Inhibition of esterification presumably follows
      accumulation of extramitochondrial alkylthioacryloyl-CoA, an inhibitor of
      microsomal glycerophosphate acyltransferase. (14) 9-Thia stearate is a strong
      inhibitor of the delta 9-desaturase in liver and 10-thia stearate of
      dihydrosterculic acid synthesis in trypanosomes. (15) Some attempts to develop
      thia fatty acids as drugs are also reviewed.

PMID- 9030190
TI  - Effect of carbonyl cyanide m-chlorophenylhydrazone (CCCP) on the dimerization of
      lipoprotein lipase.
AB  - Lipoprotein lipase (LPL), an enzyme playing the central role in triglyceride
      metabolism, is a glycoprotein and a homodimer of identical subunits. Dimerization
      and proper processing of oligosaccharide chains are important maturation steps in
      post-translational regulation of enzyme activity. Indirect evidences suggest that
      dimerization of LPL occurs in endoplasmic reticulum (ER) or Golgi. In this study,
      we investigated the dimerization status of LPL in 3T3-L1 adipocytes, using
      sucrose density gradient ultracentrifugation and carbonyl cyanide m
      chlorophenylhydrazone (CCCP), an inhibitor of ER-Golgi protein transport. In the
      presence of CCCP, no increase of cellular LPL activity was detected during 2 b of
      recovery period after the depletion of LPL, with heparin and cycloheximide. Only
      endoglycosidase H (endo H)-sensitive subunits were found in CCCP-treated cells
      after endo H digestion, suggesting that inactive LPL was retained in ER. In the
      presence of castanospermine, an inhibitor of ER glucosidase I, LPL subunits of
      both control and CCCP-treated cells had same molecular weight, indicating that
      complete oligosaccharides were transferred to LPL subunits in the presence of
      CCCP. In sucrose density gradient ultracentrifugation, all the LPL protein
      synthesized in the presence of CCCP was found at the dimeric fractions as in
      control cells. Most of LPL protein in control cells showed high affinity for
      heparin, and there was no difference between the control and CCCP-treated cells.
      These results suggest that dimerization and acquisition of high affinity for
      heparin of LPL can occur in ER of CCCP-treated cells without acquisition of
      catalytic activity.

PMID- 9030191
TI  - Characterization of human apolipoprotein A-I expressed in Escherichia coli.
AB  - Human apolipoprotein A-I (apoA-I), with an additional N-terminal extension (Met
      Arg-Gly-Ser-(His)6-Met) (His-apoA-I), has been produced in Escherichia coli with
      a final yield after purification of 10 mg protein/1 of culture medium. We have
      characterized the conformation and structural properties of His-apoA-I in lipid
      free form, and in reconstituted lipoproteins containing two apoA-I per particle
      (Lp2A-I) by both immunochemical and physicochemical techniques. The lipid-free
      forms of the two proteins present very similar secondary structure and stability,
      and have also very similar kinetics of association with dimyristoyl
      phosphatidylcholine. His-apoA-I and native apoA-I can be complexed with 1
      palmitoyl-2-oleoyl phosphatidylcholine (POPC) to form similar, stable, either
      discoidal or spherical (sonicated) Lp2A-I particles. Lipid-bound native apoA-I
      and His-apoA-I showed very similar alpha-helical content (69% and 66%,
      respectively in discoidal Lp2A-I and 54% and 51%, respectively in spherical Lp2A
      I). The conformation of His-apoA-I in lipid-free form and in discoidal or
      spherical Lp2A-I has also been shown to be similar to native apoA-I by
      immunochemical measurements using 13 monoclonal antibodies recognizing distinct
      apoA-I epitopes. In the free protein and in reconstituted Lp2A-I, the N-terminal
      has no effect on the affinity of any of the monoclonal antibodies and minimal
      effect on immunoreactivity values. Small differences in the exposure of some apoA
      I epitopes are evident on discoidal particles, while no difference is apparent in
      the expression of any epitope of apoA-I on spherical Lp2A-I. The presence of the
      N-terminal extension also has no effect on the reaction of LCAT with the
      discoidal Lp2A-I or on the ability of complexes to promote cholesterol efflux
      from fibroblasts in culture. In conclusion, we show that His-apoA-I expressed in
      E. coli exhibits similar physicochemical properties to native apoA-I and is also
      identical to the native protein in its ability to interact with phospholipids and
      to promote cholesterol esterification and cellular cholesterol efflux.

PMID- 9030192
TI  - Glucose-responsitivity and expression of an ATP-stimulatable, Ca(2+)-independent
      phospholipase A2 enzyme in clonal insulinoma cell lines.
AB  - We have previously reported that pancreatic islet beta-cells and clonal HIT
      insulinoma cells express an ATP-stimulatable Ca(2+)-independent phospholipase A2
      (ASCI-PLA2) enzyme and that activation of this enzyme appears to participate in
      glucose-stimulated insulin secretion. To further examine this hypothesis, glucose
      responsitivity and expression of ASCI-PLA2 activity in various insulinoma cell
      lines were examined. Secretagogue-stimulated insulin secretion was observed with
      beta TC6-f7 and early passage (EP)-beta TC6 cells. In contrast, RIN-m5f, beta
      TC3, and late passage (LP)-beta TC6 cells exhibited little secretagogue-induced
      secretion. A haloenollactone suicide substrate (HELSS) which inhibits ASCI-PLA2
      activity ablated secretagogue-induced insulin secretion from beta TC6-f7 and EP
      beta TC6 cells. All insulinoma cell lines studied expressed both cytosolic and
      membrane-associated Ca(2+)-independent PLA2 activities which were inhibited by
      HELSS. The cytosolic enzymatic activity in the glucose-responsive beta TC6-f7 and
      EP-beta TC6 cells was activated by ATP and protected against thermal denaturation
      by ATP, but this was not the case in the glucose-unresponsive RIN-m5f, beta TC3,
      or LP-beta TC6 cells. Comparison of the distribution of Ca(2+)-independent PLA2
      activity revealed that membrane-associated activity was higher than cytosolic
      activity in beta TC6-f7 and EP-beta TC6 cells but not in RIN-m5f, beta TC3, or LP
      beta TC6 cells. Insensitivity of cytosolic activity to ATP may prevent
      association of the PLA2 activity with membrane substrates and contribute to
      attenuated glucose-responsitivity in the RIN-m5f, beta TC3, or LP-beta TC6 cells.
      HIT insulinoma cells were also found to undergo a decline in both glucose
      responsitivity and membrane-associated Ca(2+)-independent PLA2 activity upon
      serial passage in culture, and this was associated with a reduction in membrane
      content of arachidonate-containing phospholipids. These and previous results
      suggest that the ATP-stimulatable PLA2 enzyme may participate in glucose-induced
      insulin secretion.

PMID- 9030193
TI  - Coupling of ethanol metabolism to lipid biosynthesis: labelling of the glycerol
      moieties of sn-glycerol-3-phosphate, a phosphatidic acid and a
      phosphatidylcholine in liver of rats given [1,1-2H2]ethanol.
AB  - The mechanism behind ethanol-induced fatty liver was investigated by
      administration of [1,1-2H2]ethanol to rats and analysis of intermediates in lipid
      biosynthesis. Phosphatidic acid and phosphatidylcholine were isolated by
      chromatography on a lipophilic anion exchanger and molecular species were
      isolated by high-performance liquid chromatography in a non-aqueous system. The
      glycerol moieties of palmitoyl-linoleoylphosphatidic acid, the corresponding
      phosphatidylcholine and free sn-glycerol-3-phosphate were analysed by GC/MS of
      methyl ester t-butyldimethylsilyl derivatives. The deuterium labelling in the
      glycerol moiety of the phosphatidic acid was 2-3-times higher than in free sn
      glycerol-3-phosphate, indicating that a specific pool of sn-glycerol-3-phosphate
      was used for the synthesis of phosphatidic acid in liver. The results indicate
      that NADH formed during ethanol oxidation is used in the formation of a pool of
      sn-glycerol-3-phosphate that gives rise to triacylglycerol and possibly fatty
      liver.

PMID- 9030194
TI  - Characterization of alpha 2-macroglobulin receptor low density lipoprotein
      receptor-related protein (alpha 2 MR/LRP) in White Carneau pigeon peritoneal
      macrophages: its role in lipoprotein metabolism.
AB  - White Carneau pigeons develop atherosclerosis naturally, and at an accelerated
      rate with cholesterol feeding. Macrophages play a central role in the
      pathogenesis of atherosclerosis in pigeons, as they do in man. The purpose of
      this study was to determine whether pigeon macrophages express the alpha 2
      macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2
      MR/LRP) and whether this receptor would recognize beta-VLDL, the major
      cholesterol-transporting lipoprotein in cholesterol-fed pigeons. The binding of
      125I-methylamine-treated alpha 2M (125I-alpha 2 M+) at 4 degrees C was saturable
      (> 10 nM), specific, Ca2+ dependent, was competed for by the receptor-associated
      protein (RAP), and had a Kd of binding of 1-5.6 nM, similar to mouse peritoneal
      macrophages studied simultaneously. At 37 degrees C the bound 125I-alpha 2 M+ was
      rapidly internalized and degraded in lysosomes. The binding of alpha 2 M+ was not
      down-regulated with cholesterol loading, as is the LDL receptor on pigeon
      macrophages. At 4 degrees C there was no competition for binding of 125I-alpha 2
      M+ by either pigeon or rabbit beta-VLDL, nor was binding of 125I-pigeon or rabbit
      beta-VLDL competed for by alpha 2 M+. Stimulation of cholesterol esterification
      by rabbit or pigeon beta-VLDL was unaffected by RAP, lactoferrin, or alpha 2 M+.
      Metabolism of 125I-pigeon or rabbit beta-VLDL was not competed by RAP,
      lactoferrin, or alpha 2 M+ even in the presence of lipoprotein lipase. Pigeon
      macrophages, and a 500 kDa membrane protein isolated from them, were recognized
      by several antihuman alpha 2 MR/LRP monoclonal antibodies. The 500 kDa membrane
      protein also bound 45Ca. These data suggest considerable sequence homology with
      the human alpha 2 MR/LRP. This is the first study to characterize a functional
      alpha 2 MR/LRP on peritoneal macrophages from an avian species. There was no
      evidence, however, that the alpha 2 MR/LRP mediates uptake of beta-VLDL by pigeon
      macrophages.

PMID- 9030195
TI  - Macrophage arachidonate release via both the cytosolic Ca(2+)-dependent and 
      independent phospholipases is necessary for cell spreading.
AB  - We have observed that phospholipase A2 (PLA2) activation and arachidonate (AA)
      release are essential for monocyte/macrophage adherence and spreading. In this
      study, we addressed the relationship between AA release and cell
      adherence/spreading in murine resident peritoneal macrophages, and the roles of
      specific PLA2S in these processes. The PLA2-specific inhibitors, (E)-6
      (bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BEL, specific for
      the Ca(2+)-independent PLA2 (iPLA2)) and methyl arachidonoyl fluorophosphonate
      (MAFP, specific for the Ca(2+)-dependent phospholipase (cPLA2)) inhibited AA
      release and cell spreading in a correlated fashion but only modestly decreased
      cell adherence. Cell spreading was normalized by the addition of AA to PLA2
      inhibited cells. AA release during spreading was also inhibited by Ca2+ depletion
      or protein kinase C (PKC) inhibition, and was accompanied by increased (but
      transient) phosphorylation of cPLA2-Inhibition of macrophage spreading, however,
      only partially inhibited AA release. Moreover, constitutive AA release was seen
      in fully spread macrophages which was inhibited by BEL, but not MAFP or Ca2+
      depletion. BEL also reversed the phenotype of fully spread cells. These data
      suggest that macrophage spreading requires the release of AA by the iPLA2 (which
      appears to be constitutively active) and cPLA2 (which appears to be stimulated by
      adherence/spreading). Maintenance of macrophage spreading, in contrast, appears
      to be principally dependent on the iPLA2.

PMID- 9030196
TI  - RAB GTPases expressed in human melanoma cells.
AB  - The expression of small GTP-binding protein genes of the ras superfamily was
      examined in pigmented human melanoma cells by a PCR-based strategy. Twenty six
      different partial cDNA sequences were isolated, including 17 members of the rab
      subfamily, of which 9 represented novel genes. Some rabs expressed in melanoma
      cells overlapped with those of platelets: this should prove relevant to the
      investigation of murine and human disorders characterized by the combination of
      pigment dilution and a platelet storage pool defect.

PMID- 9030197
TI  - Improved oligonucleotide uptake and stability by a new drug carrier, the
      SupraMolecular Bio Vector (SMBV).
AB  - Antisense oligodeoxynucleotides are potential therapeutic agents, but their
      development is still limited by both a poor cellular uptake and a high
      degradation rate in biological media. The strategy that we propose to face these
      problems is to use small synthetic carriers, around 30 nm diameter, the
      SupraMolecular Bio Vectors (SMBV). We used positively charged SMBV and settled
      the ionic incorporation of negatively charged oligonucleotides into these
      carriers. A minimal leakage of 10% of total incorporated oligonucleotides was
      then measured during two months. Both protection and uptake of oligonucleotides
      were then analyzed. On the one hand, we showed that the incorporation of
      oligonucleotides into the selected SMBV allows to significantly increase, 8
      times, their half-life, in cell growth medium. On the other hand, the
      internalization of the SMBV, into cells, by an endosomal pathway has been
      characterized. The essential point is that the SMBV uptake elicits the
      simultaneous oligonucleotide uptake. The oligonucleotide amount that goes through
      cells within 5 h can be up to 30 times higher than for free oligonucleotides and
      the fraction of oligonucleotides that is present in the cytosol is increased up
      to 10 fold after incorporation into the SMBV. This study demonstrates the ability
      of SMBV to improve oligonucleotide cellular behaviour.

PMID- 9030198
TI  - Differential expression of membrane-anchored proteoglycans in rabbit articular
      chondrocytes cultured in monolayers and in alginate beads. Effect of transforming
      growth factor-beta 1.
AB  - Cell-surface proteoglycans (PGs) were extracted with Triton X-100 from rabbit
      articular chondrocytes cultured in monolayers and in alginate beads. They were
      first purified on DEAE-Trisacryl columns and the proportion of hydrophobic PGs
      was determined by both Octyl-Sepharose chromatography and partitioning in Triton
      X-114. These two methods revealed that the proportion of hydrophobic PGs was
      higher in monolayer culture system as compared to alginate beads (24 and 15%,
      respectively). Characterization of the PGs by Sepharose CL 6B gel filtration
      followed by electrophoresis indicated that the PGs isolated from monolayers were
      composed of three chondroitin sulfate (CS) PGs (core proteins of 180, 100 and 50
      kDa) and a heparan sulfate (HS) PG (core protein of 60 kDa). In the alginate
      system. CSPGs with core proteins of 180, 45 and 32 kDa were observed, but no HSPG
      was present. In parallel, the effect of TGF-beta on the distribution of membrane
      associated PGs was studied. The results showed that the synthesis of cell-surface
      PGs was stimulated by TGF-beta in monolayers whereas it was inhibited in alginate
      beads, but the amount of hydrophobic PGs was not altered by the growth factor.
      These data clearly indicate that TGF-beta induces a differential expression of
      the PG families present at the cell surface. Taken together, the results reveal
      the complex regulation of cell-surface PG distribution, which obviously depends
      on the culture method used and suggest that rabbit articular chondrocytes may
      differentially respond to extracellular ligands according to their morphological
      state and environment.

PMID- 9030199
TI  - Conductive Na+ transport in fetal lung alveolar apical membrane vesicles is
      regulated by fatty acids and G proteins.
AB  - We have characterised G protein and fatty acid regulation of the Na+ conductance
      in purified apical membrane vesicles prepared from late gestation fetal guinea
      pig lung. Addition of 100 microM GTP gamma S or beta gamma-methylene-GTP,
      irreversible G protein activators, stimulated conductive 22Na+ uptake (ratio of
      experimental to control 1.35 +/- 0.02 and 1.34 +/- 0.05, respectively).
      Conversely, the addition of GDP beta S, an irreversible G protein inhibitor,
      reduced conductive 22Na+ uptake from 1.00 (control) to 0.79 +/- 0.04. A range of
      saturated (myristic, palmitic, stearic), monounsaturated (elaidic, oleic) and
      polyunsaturated (linoleic, arachidonic) fatty acids all stimulated conductive
      22Na+ uptake, by between 1.18 +/- 0.05 to 1.56 +/- 0.13 over the control. Both
      arachidonic acid and GTP gamma S-dependent stimulation were abolished in the
      presence of 10 microM amiloride. The non-metabolisable analogue of arachidonic
      acid, eicosa-5,8,11,14-tetraynoic acid also stimulated conductive 22Na+ uptake.
      Furthermore, addition of indomethacin and nordihydroguairetic acid, inhibitors of
      cyclooxygenase and lipoxygenase pathways of arachidonate metabolism respectively,
      did not affect the arachidonic acid stimulation suggesting a direct effect of
      fatty acid upon the Na+ channel Since mepacrine (50 microM), a phospholipase A2
      inhibitor, did not affect the GTP gamma S-stimulated conductive 22Na+ uptake, and
      inhibition of G protein turnover by GDP beta S did not attenuate the arachidonic
      acid response we conclude that these two regulatory pathways modulate alveolar
      Na+ transport directly and independently of each other.

PMID- 9030200
TI  - Modulation of cytokine production by human mononuclear cells following impairment
      of Na, K-ATPase activity.
AB  - Cytokines, including TNF alpha and IL-l beta, are central to the chronic
      inflammatory process and tissue damage that characterises diseases such as
      rheumatoid arthritis. The mechanisms responsible for long-term generation of
      these molecules are poorly understood. We have previously demonstrated impaired
      activity of Na, K-ATPase, a key enzyme regulating intracellular cation levels, on
      rheumatoid mononuclear cells. Mimicking this 'defect' on normal mononuclear cells
      with ouabain has been shown to induce TNF alpha and, in particular, IL-l beta
      production, whereas IL-6 synthesis was suppressed. A similar pattern of cytokine
      generation was noted when mononuclear cells were treated with the sodium
      ionophore, monensin. Induction of cytokine production was related to up
      regulation of the appropriate mRNA, although enhanced secretion of processed IL-l
      beta was also observed. The mechanism underlying these cellular responses appears
      to involve sodium/calcium exchange across the cell membrane. Impaired Na,K-ATPase
      activity might promote pro-inflammatory cytokine secretion in patients with
      rheumatoid arthritis.

PMID- 9030201
TI  - Re-investigation of glucose metabolism in Fibrobacter succinogenes, using NMR
      spectroscopy and enzymatic assays. Evidence for pentose phosphates
      phosphoketolase and pyruvate formate lyase activities.
AB  - The glucose metabolism of Fibrobacter succinogenes S85 was studied in detail; key
      intermediates and alternative pathways were evidenced by NMR and/or enzymatic
      assays. A high phosphoketolase activity was detected in four strains of
      Fibrobacter under strictly anaerobic conditions, with ribose-5-phosphate as
      substrate, no activity was evidenced with fructose-6-phosphate. This is the first
      report of a pentose phosphates phosphoketolase in bacteria unable to use
      pentoses. In contrast, the Entner-Doudoroff pathway and the oxidative branch of
      the pentose phosphate pathway could not be evidenced. Incubation of living cells
      of F. succinogenes with Na2(13)CO3 confirmed the incorporation of 13CO2 in the
      carboxylic group of succinate. The presence of fumarase was evidenced by in vivo
      4C-NMR using 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO): the enzyme showed a high
      reversibility under physiological conditions. The production of formate from
      glucose catabolism was evidenced by enzymatic assay and by NMR and a pyruvate
      formate lyase activity was detected using strictly anaerobic conditions.

PMID- 9030203
TI  - Studies on ether-phospholipids of vascular smooth muscle cells. Identification of
      a rapid Ca(2+)-dependent hydrolysis of alkyl-phosphatidylethanolamine promoted by
      endothelin-l.
AB  - We have investigated the metabolism of 1-O-[3H]octadecyl-sn-glycero-3
      phosphocholine ([3H]lyso PAF) and [3H] myristic acid in secondary cultures of
      aortic smooth muscle cells (SMC) to characterize the origin of second messengers
      generated upon stimulation with endothelin-l (ET-l). When cells were labelled
      with [3H]lyso PAF, we observed a transfer of the label from phosphatidylcholine
      (PC) to phosphatidylethanolamine (PE) In contrast, incubation with [3H]lyso PAF
      labelled mainly alkyl-subclasses while [3H]myristate was associated with diacyl
      subclasses. Using these specific labelling procedures, we have shown that ET-l
      induced a strong hydrolysis of PE. This hydrolysis was specific for alkyl-PE with
      a maximum after 5 s of stimulation. We have also observed an extracellular Ca(2+)
      dependent increase in diglyceride (DG), phosphatidic acid (PA) and mainly
      triglyceride (TG) concomitant to alkyl-PE hydrolysis. Thus, alkyl-DG generated
      from alkyl-PE appears to be a major product in ET-l stimulation of SMC. These
      results suggest a new level of complexity in the signal transduction cascade
      involving a specificity for phospholipid subclasses.

PMID- 9030202
TI  - Caffeine decreases intracellular free Mg2+ in isolated adult rat ventricular
      myocytes.
AB  - Caffeine has been extensively used to study intracellular Ca2+ control and
      contraction-relaxation in cardiomyocytes. The effects of caffeine on
      intracellular free Mg2+ concentration, [Mg2+]i, were studied in isolated adult
      rat ventricular myocytes by fluorescent techniques using mag-fura-2. Basal
      [Mg2+]i was 0.62 +/- 0.02 mM, n = 54, in quiescent cells and 0.73 +/- 0.02 mM, n
      = 23, in electrically-stimulated adult rat ventricular myocytes. Caffeine, 20 mM,
      significantly decreased [Mg2+] in both quiescent (-0.17 +/- 0.01 mM) and
      electrically-stimulated (-0.16 +/- 0.01 mM) adult ventricular myocytes.
      Ryanodine, a blocker for Ca(2+)-release channels of the sarcoplasmic reticulum,
      did not have any effect on basal [Mg2+]i, 0.67 +/- 0.02 mM nor on caffeine
      induced reduction in [Mg2+]i, -0.16 +/- 0.01 mM in quiescent cardiomyocytes or
      electrically-stimulated cells; 0.74 +/- 0.03 mM and -0.11 +/- 0.03 mM,
      respectively. Ruthenium red, an inhibitor of mitochondrial Ca2+ uptake, also
      failed to alter basal [Mg2+]i, or caffeine-induced reduction in [Mg2+], in either
      quiescent or electrically-stimulated cells. The effects of caffeine on [Mg2+]i,
      may be important in considering the use of this drug to study
      contraction/function studies in heart cells.

PMID- 9030204
TI  - Effects of U73122 and U73343 on human platelet calcium signalling and protein
      tyrosine phosphorylation.
AB  - We have investigated the actions of the PLC inhibitor, U73122, and its close
      analogue, U73343, which does not inhibit PLC, in Fura-2-loaded human platelets.
      Rises in [Ca2+]i evoked by thrombin and collagen, and the TxA2-dependent rise in
      [Ca2+]i evoked by thapsigargin, were abolished by U73122, indicating that it
      inhibits the activity of both beta and gamma isoforms of PLC. The supposed
      control compound U73343, was found to inhibit TxA2 formation; it therefore
      partially inhibited the rise in [Ca2+]i evoked by low concentrations of thrombin,
      by thapsigargin or by collagen. U73343 had a greater effect than aspirin on the
      action of collagen, indicating an action on the TxA2-independent component of the
      signal, via PLC gamma-U73343 lowered TxA2 production by inhibiting the activation
      of cPLA2, probably at a tyrosine phosphorylation step. U73343 seems to inhibit
      only the tyrosine kinases involved in the activation of PLC gamma and the
      generation of TxA2. In contrast, U73122 increased tyrosine phosphorylation of
      platelet proteins, perhaps by inhibiting receptor independent tyrosine
      phosphatases, but inhibited all further tyrosine phosphorylation on addition of
      thrombin or other agonists.

PMID- 9030205
TI  - Ca2+ release and Ca2+ influx in Chinese hamster ovary cells expressing the cloned
      mouse B2 bradykinin receptor: tyrosine kinase inhibitor-sensitive and-
      insensitive processes.
AB  - A cDNA encoding a mouse B2 bradykinin (BK) receptor was stably transfected in
      Chinese hamster ovary (CHO) cells. In two resulting transformants, mouse B2 BK
      receptor was found to induce a twofold elevation in the inositol-1,4,5
      trisphosphate level. In a pertussis toxin-insensitive manner, BK also produced a
      biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i). The initial
      elevation in [Ca2+]i was abolished by thapsigargin pretreatment in Ca(2+)-free
      medium. The second phase was dependent on external Ca2+. The BK/inositol
      trisphosphate and thapsigargin-sensitive Ca2+ stores required extracellular Ca2+
      for refilling. Ca2+ influx induced by BK and thapsigargin was confirmed by Mn2+
      entry through Ca2+ influx pathways producing Mn2+ quenching. Genistein, a
      tyrosine kinase inhibitor, partially decreased the BK-induced [Ca2+]i increase
      during the sustained phase and the rate of Mn2+ entry. BK had essentially no
      effect on the intracellular cyclic AMP level. The results suggest that the mouse
      B2 BK receptor couples to phospholipase C in CHO cells and that its activation
      results in biphasic [Ca2+]i increases, by mobilization of intracellular Ca2+ and
      store-depletion-mediated Ca2+ influx, the latter of which is tyrosine
      phosphorylation dependent.

PMID- 9030206
TI  - Identification of NAP-22 and GAP-43 (neuromodulin) as major protein components in
      a Triton insoluble low density fraction of rat brain.
AB  - NAP-22 is a membrane-localized brain enriched acidic protein having a Ca(2+)
      dependent calmodulin binding activity. Further fractionation of the NAP-22
      containing membrane showed the localization of NAP-22 in a Triton insoluble
      fraction of low density. Besides NAP-22, this fraction was found to contain GAP
      43 (neuromodulin), trimeric G proteins, and some GPI-anchored proteins such as
      Thy-1 and N-CAM-120. Presence of some protein tyrosine kinases, such as src and
      fyn, was also shown.

PMID- 9030207
TI  - Cloning, functional expression and tissue distribution of rabbit alpha 1d
      adrenoceptor.
AB  - We have cloned a cDNA encoding rabbit alpha 1d-adrenoceptor from the rabbit liver
      cDNA library. The deduced amino-acid sequence of this clone encodes a protein of
      576 amino acids that shows strong sequence homology to previously cloned human,
      rat and mouse alpha 1d-adrenoceptors. The pharmacological radioligand binding
      properties of this clone expressed in COS-7 cells were similar to those of rat
      alpha 1d-adrenoceptors. Competitive RT/PCR assays revealed wide tissue
      distribution of the alpha 1d-adrenoceptor mRNA in rabbit, especially abundant in
      vas deferens, aorta, prostate and cerebral cortex.

PMID- 9030209
TI  - Ionic calcium content of light dense human red cells separated by Percoll density
      gradients.
AB  - In this paper we have compared the adequacy of two methods using Percoll density
      gradients to separate light and dense erythrocytes from fresh human blood. After
      measuring the distribution of some classical age-markers such as haemoglobin,
      potassium and creatine contents, it was found that preformed gradients generated
      more stringent conditions for age-related density separations. Employing such
      gradients the free Ca2+ content of above sub-populations was assessed with Fura
      2, under conditions where the viscosity effect was abolished. In five
      experiments, the free Ca2+ content (mean value +/- 1 S.D.) was 8.4 +/- 2.82 nM
      and 31.2 +/- 13.0 nM for the 7-10% lightest and densest cells, respectively.
      These results are discussed in connection to red cell senescence.

PMID- 9030208
TI  - The platelet-activating factor acetylhydrolase of mouse platelets.
AB  - Platelet-activating factor (PAF) acetylhydrolases are a family of distinct
      enzymes with the common property of hydrolyzing and inactivating PAF. It has been
      shown that the structure and the biochemical behavior of these enzymes depend on
      their cellular origin. We studied the PAF acetylhydrolase activity in mouse
      platelets in order to investigate the unusual response of these platelets to PAF.
      We found that mouse platelets contain a PAF acetylhydrolase with an apparent Km
      value of 0.8 microM, suggesting a very high affinity for PAF. Contrary to other
      normal mammalian cells and tissues, mouse platelet PAF acetylhydrolase is almost
      equally distributed in the membranes and the cytosol and is characterized by an
      extreme sensitivity to heating. The enzyme requires the presence of
      dithioerythritol for maximal activity, it is affected by 5,5'-dithiobis(2
      nitrobenzoic acid) and N-ethylmaleimide and it is strongly inhibited by
      phenylmethylsulfonylfluoride. We purified, to near homogeneity, the PAF
      acetylhydrolase from mouse platelet membranes and demonstrated that it is a
      protein relatively abundant in the membranes with an apparent molecular weight of
      270 kDa. Electrophoretic analysis, under reducing conditions, revealed four bands
      and one duplet with molecular weights of 66, 55, 52, 49 and 62 kDa. respectively.
      Thus, PAF hydrolysis in mouse platelets is mediated by a PAF acetylhydrolase
      having biophysical and biochemical properties more intricate than those of the
      PAF acetylhydrolases found in other species.

PMID- 9030210
TI  - Interaction of surfactants with DNA. Role of hydrophobicity and surface charge on
      intercalation and DNA melting.
AB  - A probe, 9-(anthrylmethyl)trimethylammonium chloride, 1. was prepared, 1 binds to
      caF-thymus DNA or Escherichia coli genomic DNA with high affinity, as evidenced
      from the absorption titration. Strong hypochromism, spectral broadening and red
      shifts in the absorption spectra were observed. Half-reciprocal plot constructed
      from this experiment gave binding constant of 5 +/- 0.5 x 10(4) M-1 in base
      molarity. We employed this anthryl probe-DNA complex for studying the effects of
      addition of various surfactant to DNA. Surfactants of different charge types and
      chain lengths were used in this study and the effects of surfactant addition to
      such probe-DNA complex were compared with that of small organic cations or salts.
      Addition of either salts or cationic surfactants led to structural changes in DNA
      and under these conditions, the probe from the DNA-bound complex appeared to get
      released. However, the cationic surfactants could induce such release of the
      probe from the probe-DNA complex at a much lower concentration than that of the
      small organic cations or salts. In contrast the anionic surfactants failed to
      promote any destabilization of such probe-DNA complexes. The effects of additives
      on the probe-DNA complexes were also examined by using a different technique
      (fluorescence spectroscopy) using a different probe ethidium bromide. The
      association complexes formed between the cationic surfactants and the plasmid DNA
      pTZ19R, were further examined under agarose gel electrophoresis and could not be
      visualized by ethidium bromide staining presumably due to cationic surfactant
      induced condensation of DNA. Most of the DNA from such association complexes can
      be recovered by extraction of surfactants with phenol-chloroform. Inclusion of
      surfactants and other additives into the DNA generally enhanced the DNA melting
      temperatures by a few degrees C and at high [surfactant], the corresponding
      melting profiles got broadened.

PMID- 9030211
TI  - Interaction of substrates with the intestinal brush border membrane Na/phosphate
      cotransporter.
AB  - The interaction of Na+ and phosphate with the intestinal brush border membrane
      Na+/phosphate cotransporter was examined using stopped-flow tryptophan
      fluorescence and ion-exchange Dowex columns coupled to a light-activated
      microsecond timer (LAM timer) which measures exchange kinetics between protein
      bound ions and the external medium Na+ or Na+ + H2PO4- induced tryptophan
      fluorescence quenching with apparent rate constants of 35 s-1 and 13 s-1,
      respectively. Dilution of substrate-bound cotransporter resulted in tryptophan
      fluorescence recovery consistent with cotransporter return to the substrate-free
      conformation. Recovery of the substrate-free conformation was slow (1.6 s-1) in
      the absence of phosphate, was accelerated by H2PO4 (7 s-1) and was inhibited by
      HPO4(2) (1.1 s-1). The effects of substrates on tryptophan fluorescence were
      sensitive to substrate site blockers consistent with tryptophan fluorescence
      monitoring cotransporter conformations and substrate-induced changes in
      conformation. Equivalent experiments using the LAM timer and either (22Na+) or
      Na+ + (32P) phosphate verified the rate constants for the substrate-induced
      quenching of tryptophan fluorescence, suggested that 2 Na+ 's were occluded by
      the cotransporter as part of the Na(+)-induced conformational change and that
      H2PO4 accelerated deocclusion of Na+. The association of phosphate with the
      cotransporter was also examined. Although cotransporter-bound phosphate was
      medium anion-insensitive, a cotransporter conformational change preceding the
      release of phosphate from the cotransporter was not observed. However, three
      lines of evidence suggest that release of phosphate from the cotransporter
      involved a unique cotransporter conformation which may suggest that phosphate was
      also occluded by the intestinal brush border Na+/phosphate cotransporter.

PMID- 9030212
TI  - Lipid mixing in dimyristoyl phosphatidylcholine-dimyristoyl glycerol dispersions:
      spin label ESR studies.
AB  - The lipid transfer and mixing properties in hydrated dispersions of dimyristoyl
      phosphatidylcholine (DMPC)/dimyristoyl glycerol (DMG) binary mixtures have been
      investigated by using electron spin resonance spectroscopy of the spin-labelled
      lipid components. The assay system is based on the reduction in spectral
      broadening from spin-spin interactions that takes place by dilution of the spin
      labelled lipid on transfer to a 9-fold excess of dispersions that contain no spin
      label. Lipid dispersions with DMPC:DMG compositions of 70:30, 40:60 and 20:80
      mol/mol, for which the fluid phases have lamellar, inverted hexagonal and
      isotropic structures, respectively, have been studied. Essentially no transfer of
      spin-labelled lipid takes place for any of the lipid mixtures in the lamellar gel
      phase, or in dispersions of DMPC alone at all temperatures studied. The greatest
      degrees of transfer are found in the fluid phase of the DMPC/DMG mixtures. In
      general, the extent of lipid transfer is greater for the diacylglycerol component
      than for the phosphatidylcholine component. The extent of transfer of
      phosphatidylcholine is very low in the fluid lamellar phase of the 70:30 mol/mol
      DMPC/DMG, as compared with that of diacylglycerol. Only in the case of the 40:60
      mol/mol DMPC/DMG mixture, in the inverted hexagonal phase, are the extents of
      transfer comparable for both phosphatidylcholine and diacylglycerol components,
      indicating a bulk transfer of lipid within the dispersions. The largest extent of
      transfer is found for diacylglycerol in the 20:80 mol/mol DMPC/DMG mixture in the
      isotropic phase.

PMID- 9030213
TI  - Regulation of membrane lipid bilayer structure during seasonal variation: a study
      on the brain membranes of Clarias batrachus.
AB  - (1) A significant seasonal variation in the membrane fluidity (as sensed by DPH
      fluorescence polarization), membrane lipid components (phospholipid and neutral
      lipid), fatty acid composition of membrane phospholipid (phosphatidylcholine,
      phosphatidylethanolamine and sphingomyelin), positional distribution of fatty
      acids at Sn-1 and Sn-2 position of phosphatidyl-choline and -ethanolamine is
      noticed in the brain membranes (myelin, synaptosomes, and mitochondria) of a
      tropical air breathing teleost, Clarias batrachus. (2) A 'partial compensation'
      of membrane fluidity during seasonal adaptation is observed in myelin and
      mitochondria membrane fractions. Synaptosomes membrane fraction exhibits a
      different response. Depletion (about 15-70%) of membrane lipid components
      (phospholipid, cholesterol, diacylglycerol and triacylglycerol) per unit of
      membrane protein is the characteristic feature of summer adaptation. An increase
      (about 20-100%) in the level of oleic acid and decrease (about 20-60%) in the
      level of stearic acid are almost common features in membrane phospholipid
      fractions of winter-adapted Clarias (3) From the tissue slice experiment it is
      evident that there is an activation of cellular phospholipase A2 at lower growth
      temperature and of cellular phospholipase A1 at higher growth temperature and
      this suggests the reorganization of molecular architecture of the membrane during
      seasonal adaptation. (4) Accumulation of oleic acid in Sn-1 position and
      polyunsaturated fatty acids in Sn-2 position of phosphatidylcholine and 
      ethanolamine during winter indicates an increase in the concentration of 1
      monoenoic, 2-polyenoic molecular species of phospholipid in order to maintain the
      stability of membrane lipid bilayer.

PMID- 9030214
TI  - Chilling stress leads to increased cell membrane rigidity in roots of coffee
      (Coffea arabica L.) seedlings.
AB  - Tropical and sub-tropical higher plant species show marked growth inhibition when
      exposed to chilling temperatures. In root tip segments of coffee seedlings which
      were subjected for 6 days to temperatures of 10, 15, 20 and 25 degrees C, in
      darkness, we have detected an increased amount of malondialdehyde formed in the
      10 degrees C treatment, accompanied by higher electrolyte leakage. The electron
      paramagnetic resonance (EPR) technique and the fatty acid spin probes 5-, 12- and
      16-doxylstearic acid were used to assess cellular membrane fluidity. At the depth
      of the 5th and 16th carbon atom of the alkyl chains the nitroxide radical
      detected more rigid membranes in seedlings subjected to 10 degrees C compared
      with 15 and 25 degrees C. At the C-12 position of the chains the probe showed
      very restricted motion and was insensitive to chilling induced membrane
      alterations. EPR parameters for intact tissues and microsome preparations from
      root tips showed that the fluidity was essentially the same when evaluated at C-5
      and C-16 positions of the chains, and was considerably more fluid for microsomal
      membranes in the region of the C-12 position of the bilayers. The rotational
      motion of the nitroxide at C-16 position of the chains experienced a phase
      transition at about 15 degrees C. The calculated energy barriers for
      reorientational motion of the probe 16-doxylstearic acid were higher at
      temperatures of 5-15 degrees C than in the interval of 15-25 degrees C,
      suggesting that below the phase transition the membrane lipids assume a more
      ordered and compacted array. Membrane rigidity induced by chilling was
      interpreted as due to lipid peroxidation that could have been facilitated by
      higher density of peroxidizable chains below the membrane phase transition.

PMID- 9030215
TI  - Interaction of the 14-residue peptaibols, harzianins HC, with lipid bilayers:
      permeability modifications and conductance properties.
AB  - Harzianins HC are a series of 14-residue peptaibols containing three Aib-Pro
      motives separated by sequences of two usual amino acids (Aib-Pro-Xaa-Xaa)n. They
      are organized in a subtype of the 3(10)-helix, which results in an approximate
      length of about 27-30 A for the helical rods, allowing them to span a bilayer.
      Permeabilization of small unilamellar vesicles composed of zwitterionic lipids
      (egg phosphatidylcholine/cholesterol 7/3 and 8/2) by harzianins HC was observed
      as well as voltage-gated macroscopic conductance and single-channel formation in
      planar lipid bilayers (DOPE/POPC 7/3) The permeabilization process was shown to
      increase with increasing the helix global hydrophobicity. The ion channel-for
      ming properties appeared rather favoured by an increase in the peptide
      amphipathicity. The set of conductance levels increasing in geometrical
      progression, reflecting the sequential uptake and release of monomers which is
      characteristic of the barrel-stave model for ion-channels described for
      alamethicin was not observed. The passage of ions through the bilayer would
      rather be the result of a set of aggregates with fixed numbers of monomers formed
      in the bilayer. The permeability process and the voltage-gated properties could
      thus result from different mechanisms showing that harzianins HC can permeabilize
      membranes via bilayer destabilization or channels, depending on the membrane
      system, composition and application of voltage.

PMID- 9030216
TI  - Effect of polyunsaturated fatty acid deficiency on dipole relaxation in the
      membrane interface of rat liver microsomes.
AB  - The influence of a fat-free diet on the lipid dynamics of rat liver microsomes
      and liposomes of microsomal lipids was studied by using different fluorescence
      methods. Lifetime distribution and rotational diffusion of probes with different
      localization in the lipid bilayer were measured using multifrequency fluorometry.
      Lateral mobility was studied by measuring excimer formation of pyrenedodecanoic
      acid. Dipolar relaxation in the interfacial region was studied using 2-dimethyl
      amino-6-lauroylnaphthalene (Laurdan). In spite of large changes in the fatty acid
      composition of microsomal lipids, polyunsaturated fatty acid deficiency showed no
      effect on the lifetime distribution and rotational mobility of 1,6-diphenyl-1,3,5
      hexatriene (DPH). l-(4-(trimethylamino)phenyl)-6-phenyl-1,3,5-hexatriene (TMA
      DPH), 2- 7- and 12-(9-anthroiloxy)stearic acids. The treatment did not change the
      lateral diffusion of pyrenedodecanoic acid, either. However, generalized
      polarization of Laurdan fluorescence was higher in polyunsaturated fatty acid
      deficient microsomes as compared to the polyunsaturated fatty acid sufficient
      ones. This effect was also observed in liposomes of the total microsomal lipids,
      indicating that the changes in fatty acid composition resulting from
      polyunsaturated fatty acid deficiency produced a small but significant decrease
      in the rate of dipolar relaxation in the region of the lipid polar groups of the
      bilayer. The absence of lipid gel phase domains in rat liver microsomes was also
      indicated by Laurdan fluorescence features.

PMID- 9030217
TI  - The effect of lipid molecular packing stress on cationic liposome-induced rabbit
      erythrocyte fusion.
AB  - The effect of curvature stress on the efficiency of cationic liposome-induced
      fusion between rabbit erythrocytes was studied. Multilamellar cationic liposomes
      containing 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) and different PEs (1,2
      dilnoleoyl-sn-glycero-3-phosphoethanolamine (dilin-PE), 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine (DOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine
      (POPE), and lysophosphatidylethanolamine, egg (lyso-PE)) were used to induce cell
      cell fusion. It was found that high cell-cell fusion yield (FY) of about 50%
      could be achieved in sucrose solution by using cationic liposomes containing 50%
      DOTAP. Cell-cell fusion was assayed by shape criterion and was verified by
      fluorescence microscopy, using a membrane dye mixing method. The curvature
      stress, as a result of mixing unsaturated PEs in cationic liposomes, had a
      significant effect on cell-cell FY which increased with the degree of acyl chain
      unsaturation, in the order dilin-PE > DOPE > POPE > lyso-PE. Replacement of dilin
      PE, DOPE, or POPE by lyso-PE gradually in cationic liposomes lowered the cell
      cell FY from 50% to 1%. Furthermore, cationic liposome induced cell lysis, and
      fusion between cationic liposomes and cells, as assayed by the N-(lissamine
      rhodamine B sulfonyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine,
      triethylammonium salt and N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-
      dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt (Rh-PE/NBD
      PE) energy transfer method, followed the same order as that for cell-cell fusion.
      Fusion between the negatively charged PS liposomes and cationic liposomes also
      followed the same order. The electric double layer screening by electrolytes in
      NaCl-containing solution and phosphate buffered saline (PBS) was found to reduce
      the cell-cell FY and cell lysis. These findings suggest that liposome-induced
      cell-cell fusion was achieved by cationic liposomes serving as fusion-bridges
      among cells.

PMID- 9030218
TI  - Cation and anion channels in rat and human spermatozoa.
AB  - Ionic fluxes are thought to be important in the initiating process of gamete
      interaction such as acrosome reaction. Different populations of ion channels in
      rat and human spermatozoa were investigated using the planar lipid bilayer
      technique. Membrane proteins were isolated from rat and human sperm and inserted
      into lipid bilayer via fusion. We observed K(+) selective and Na(+)-selective
      channels, as well as divalent permeable cation channels in membrane preparations
      from rat sperm K+ channels, which were sensitive to the K+ channel blocker,
      tetraethylammonium (0.1 mM), exhibited a mean single channel conductance of 24
      pS. Whereas, larger conductance, 109 pS, was found to be associated with Na+
      channels. Low conductance anion channel, 15 pS, was also observed when permeant
      cations in the bathing solutions were substituted with N-methyl-D-glucamine
      leaving Cl- as the major permeant ion species. This channel exhibited a slower
      channel open and closed kinetics when compared to other cation channels. Both
      cation and anion channels with characteristics similar to that found in rat sperm
      were also observed in preparations from human sperm. The variety in the types of
      ion channels observed in rat and human spermatozoa suggests that ion channels may
      play different roles in sperm physiology and gamete interaction.

PMID- 9030219
TI  - Arylsulfonylation of bilitranslocase in plasma membranes from rat liver enables
      to discriminate between natural and artificial substrates.
AB  - The serine protease inhibitor phenylmethylsulfonyl fluoride is shown to cause
      partial inhibition of bilitranslocase transport activity in rat liver plasma
      membrane vesicles. This condition can be fully reversed by means of pyridine-2-al
      doxime methiodide, indicating that the carrier has undergone sulfonylation.
      Protection against inactivation is afforded by both bilirubin, the natural
      substrate, and nicotinic acid, but, unexpectedly, by neither sulfobromophthalein,
      the chromophoric substrate employed in bilitranslocase transport activity assay,
      nor rifamycin SV, a competitive inhibitor of sulfobromophthalein transport. From
      these protection experiments, the Ka for the complex of bilitranslocase with
      either bilirubin or nicotinic acid has been estimated to be 2.1 and 10.8 nM.
      respectively. Tentatively, the target for phenylmethylsulfonyl fluoride on
      bilitranslocase is identified as a recognition site for the physiological
      substrates.

PMID- 9030220
TI  - Role of metal ion free valinomycin-carbonyl cyanide m-chlorophenylhydrazone
      complex in the enhancement of the rates of gramicidin facilitated net H+, Li+ and
      Na+ transport across phospholipid vesicular membrane.
AB  - The studies on the decay of the pH difference, delta pH, across soyabean
      phospholipid vesicular membrane have shown that the rates of net proton transport
      and the associated Li+ and Na+ ion transport across the membrane can be enhanced
      by the combined action of gramicidin, valinomycin and carbonyl cyanide m
      chlorophenylhydrazone (CCCP) in K(+)-free vesicle solutions. The data obtained
      under different experimental conditions suggest that this enhancement is a
      consequence of facilitation of CCCP- transport (1) by complexing CCCP- with the
      highly membrane permeant valinomycin without the metal ion bound to it and (2) by
      the associated Li+ or Na+ transport through the gramicidin channel such that no
      net charge is transported across the membrane. The dissociation constant of the
      weak valinomycin-CCCP- complex has been estimated to be > 200 mM in the membrane.
      The delta pH in these experiments were created by temperature jump.

PMID- 9030221
TI  - Reconstitution of bacteriorhodopsin from a mixture of a proteinase V8 fragment
      and two synthetic peptides.
AB  - The peptide and retinal mixture of bacteriorhodopsin, composed of two synthetic
      peptides corresponding to helices F (160-197) and G (202-237) and a proteinase V8
      derived fragment V1 (1-166), generated the characteristic features of
      bacteriorhodopsin with absorbance maximum at 550 nm and fluorescence quenching as
      in two synthetic peptides corresponded to helix A (sequence 7-31) and B (41-65)
      and a chymotryptic fragment (72-248). The recovery of reconstitution estimated
      from the absorption and the fluorescence quenching of these mixture was 16-19%
      and 25-32% of the native purple membrane, respectively, whereas mixtures lacking
      any one of the peptides exhibited no absorption recovery Circular dichroism of
      each peptide fragment showed complete formation of alpha-helical structure in a
      membrane-mimetic medium of sodium dodecyl sulfate. These results indicate that
      the specific interactions or mutual recognitions between alpha-helices in lipid
      bilayers are essential for correct bundling of the seven helices and formation of
      the retinal binding pocket.

PMID- 9030222
TI  - Amphiphilic sites for general anesthetic action? Evidence from 129Xe-[1H]
      intermolecular nuclear Overhauser effects.
AB  - Because a strong correlation exists between the potency of general anesthetics
      and their ability to dissolve in oil, a lipophilic site of action is often
      assumed. We show here that a lipophilic molecule may preferentially target less
      lipophilic sites after interaction with a membrane takes place. Xenon, a
      chemically inert and structureless general anesthetic, was chosen as an unbiased
      molecular probe for assessment of its dynamic distribution. Site-selective
      intermolecular 129Xe-[1H] nuclear Overhauser effects were used to measure the
      specific interaction between xenon and protons in different regions in a
      phosphatidylcholine lipid membrane. It was evident that xenon-membrane
      interaction was directed toward the amphiphilic head region, with significant
      involvement of interfacial water, despite xenon's apolar and highly lipophilic
      nature in the gas phase. This result may suggest the importance of amphiphilicity
      in association with anesthetic action.

PMID- 9030223
TI  - [A human cell line panel for screening anti-cancer drugs].
AB  - Development of more useful screening systems for anti cancer drugs is important
      to accelerate efficiency of finding new leads. The National Cancer Institute
      (NCI) has recently developed a unique screening methodology using a human cell
      line panel. We have established a new human cell line panel according to this
      news methodology, and studied its feasibility. Concentration of a certain sample
      to inhibit proliferation of tumor cells of the panel varies and gives a
      characteristic pattern called a "finger print". Analysis of finger prints of more
      than 100 compounds, including currently used anti cancer drugs, revealed that
      finger prints appeared to be similar among drugs with the same mode of action.
      One can predict the mode of action of sample compounds by applying the above
      feature to the analysis of samples, which is the most variable advantage of this
      method. Then, one may select promising compounds by considering their effective
      concentrations and finger prints. Secondary screening by a panel of nude mice
      xenografts that correspond to cultured cell lines will follow the above
      screening. We consider that the in vitro and in vivo screening by a human cell
      line panel is a new and useful system for evaluation of anti cancer drugs.

PMID- 9030224
TI  - [Protein kinase inhibitors--screening of new molecular target therapeutics].
AB  - Protein kinases are critical enzymes in regulating cellular growth and
      differentiation. Protein tyrosine kinases are potential targets for new anti
      cancer therapeutics because they are encoded by many oncogenes. We first
      identified herbimycin A as an inhibitor of Src tyrosine kinase by screening
      agents that cause morphological reversion of v-src oncogene transformed cells. We
      next developed a method for evaluating inhibitors of oncogenic signal
      transduction pathways based on different growth abilities between normal and
      transformed cells in a defined serum free medium and isolated new tyrosine kinase
      inhibitors angelmicins. Recently, we developed an assay system in which
      activities of protein kinase A, protein kinase C, protein tyrosine kinase and
      calmodulin-dependent protein kinase III were simultaneously detected on a single
      gel. This system should be useful for evaluating specificities and screening of
      protein kinase inhibitors.

PMID- 9030225
TI  - [Anti tumor activity of farnesyl transferase inhibitor].
AB  - Posttranslational farnesylation by farnesyltransferase (FTase) is critical for
      the function of ras oncogene product and FTase has attracted attention as the new
      target of anticancer agents. B956 and B1352, obtained from the screening of CAAX
      analog inhibitors of FTase, induced flat reversion and inhibited the anchorage
      independent growth of ras transformant and ras mutated human tumor cell lines
      through the inhibition of posttranslational modification of ras p21. Inhibition
      of tumor growth in vivo was caused by inhibition of ras processing. Methyl ester
      prodrug of B956 and B1352 showed antitumor activity in ras mutated human tumor
      xenograft model. FTase inhibitor has the potential to be developed as therapy for
      ras mutated human tumors.

PMID- 9030226
TI  - [Effect of phospholipase C inhibitor peptides on cancer cell growth].
AB  - We analyzed the effect of PLC inhibitor (PCI) peptides in their growth and cell
      cycle. N-Myristoylated PCI peptide, myr-PCI, originally developed based on the
      PCI sequence of PLC-gamma 2, inhibited activity of purified PLC isoforms in
      vitro. When myr-PCI was added to KMS-4 and KMS-8 cells, both derived from
      familial adenomatous polyposis patients, it suppressed the production of inositol
      trisphosphate, DNA synthesis, and cell growth, all of which were induced by serum
      in both KMS 4 and KMS 8 cells. Flow cytometry analysis with propidium iodide
      labelling revealed marked decreases in the percentage of KMS 8 cells in S phase
      and increases in G0, G1 by the addition of myr PCI. These results indicate that
      the activation of PLC is essential for growth and transformed properties of these
      colorectal carcinoma cells, and also that PLC inhibitors could be an anti-tumor
      drug for some cases.

PMID- 9030227
TI  - [Application of NGF/PC12 cell system for screening tubulin inhibitors].
AB  - Microtubules are stiff polymers that extend throughout the cytoplasm of
      eukaryotic cells and regulate the location of intracellular compartments.
      Microtubules are formed by the polymerization of tubulin molecules, each of which
      is a heterodimer consisting of two closely related globular polypeptides, alpha
      tubulin and beta tubulin. Many of the microtubule arrays are labile and are
      turning over rapidly; they depolymerize and repolimerize continually in living
      cells. One of the most striking examples is the mitotic spindle, which forms
      after the cytoplasmic microtubules disassemble at the onset of mitosis. The
      mitotic spindle is the target of a variety of agents that act by interfering with
      the exchange of tubulin subunits between the microtubules and the free tubulin
      pool; some of these agents can be used as antimitotic or anticancer drugs. We
      recently have developed a simple and sensitive method of screening for tubulin
      inhibitors, to which we have successfully applied the nerve growth factor/PC12
      cell system. In this report, we describe the details of this method for screening
      tubulin inhibitors, by which we have analyzed several well-known and new
      compounds a model experiments.

PMID- 9030229
TI  - [Screening for the inhibitors of tumor invasion into basement membranes].
AB  - During the metastatic cascade, a tumor cell passes through several connective
      tissue barriers which consist of various adhesive molecules, such as fibronectin,
      laminin, collagens, and other glucoproteins and proteoglycans. Tumor invasion is
      a complex process involving cell adhesion, motility (migration), and the
      degradation of tissue barriers caused by the different proteases secreted by
      tumor cells. Therefore, understanding the invasion mechanism and the control
      mechanisms of the invasive properties of tumor cells may help in the development
      of anti-metastatic and anti-invasive therapies. We here focused our attention on
      the functional molecules involved in the invasive process as targets to control
      tumor metastasis, and screened the inhibitors of tumor invasion into basement
      membranes.

PMID- 9030228
TI  - [Development of anti tumor agents targeting angiogenesis].
AB  - Aberrant angiogenesis is closely involved in invasion/metastasis as well as
      enlargement of tumor. One recent highlight is to develop anti angiogenic drugs by
      targeting tumor angiogenesis. Here we describe how tumor angiogenesis is
      regulated and also recent topics related to angiogenic drug in clinical trials.

PMID- 9030231
TI  - [Present status and educational training for medical oncologist in Japan].

PMID- 9030230
TI  - [Telomere and telomerase in human cancer].
AB  - Human somatic cells gradually lose their telomeric repeats each cell division,
      and when they become critically shortened, stop dividing. On the other hand, in
      immortal cancer cells and germline cells, telomerase, a ribonucleoprotein which
      can compensate for the loss of telomeric repeats synthesizing telomeric DNA onto
      chromosomal ends, is activated and the telomere lengths are stabilized. Thus,
      telomere length and telomerase activity are believed to be characteristic
      indicators of cell proliferation and cell immortality, and inhibition of
      telomerase activity is expected to be a new strategy of anti-cancer therapy.

PMID- 9030232
TI  - [A brief overview of apoptosis].
AB  - Apoptosis is a form of cell death responsible for development and homeostasis of
      living bodies. This article summarizes the recent advent of apoptosis research in
      view of the induction factors molecular mechanism of the induction and relation
      to various diseases including cancer.

PMID- 9030233
TI  - [Involvement of ICE/CED 3 family proteases in antitumor agent-induced apoptosis].
AB  - Some chemotherapeutic agents, as well as TNF and Fas, induce apoptotic cell death
      in tumor cells, but the cellular components involved in the process have not yet
      been identified. Interleukin 1 beta converting enzyme (ICE) is a mammalian
      homolog of CED-3, a protein required for programmed cell death in nematode
      Caenorhabditis elegans. We found that a selective inhibitor of ICE/ced 3 family
      proteases, benzyloxycarbonyl Asp CH2OC(O) 2 6,-dichlorobenzene (Z-Asp-CH2-DCB).
      completely blocked the apoptotic cell death of human leukemia cells caused by
      etoposide, camptothecin, 1-beta-D-arabinofuranosyl cytosine (Ara-C) and
      adriamycin. Moreover, in antitumor agent-treated U937 cells, an ICE-like (CPP32
      like) protease was strongly activated. These results indicate that ICE/ ced 3
      family proteases are involved in antitumor agent-induced apoptosis. Activation of
      ICE family proteases plays a key role in apoptosis. However, the subsequent
      mechanisms resulting in apoptosis are largely unknown. We identified actin as a
      substrate of ICE family proteases. Cleavage of actin and other substrate proteins
      by ICE family proteases could be critical in the ongoing process of antitumor
      agent-induced apoptosis in tumor cells.

PMID- 9030235
TI  - [Development of anti cancer drugs targeted on Fas-mediated apoptosis signal].
AB  - The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) is, in part,
      executed by inducing apoptosis through the cell surface antigen Fas on the target
      cells. There are many cancer cells that resist Fas-mediated apoptosis. To
      elucidate the mechanism of this resistance is very important to understand the
      process of tumor development. We focused on FAP-1 (Fas-associated phos phatase
      1), a negative regulator of Fas-mediated apoptosis. The expression of FAP-1 was
      detected in many colon cancer cell lines. On the other hand no FAP-1 expression
      was detected in the normal colon tissue. We have found that the tri-peptide of
      Fas C-terminus inhibited the binding of Fas and FAP-1 in vitro. Microinjection of
      the tri peptide (Ac SLV) could induce Fas-mediated apoptosis in the DLD 1 human
      colon cancer cell line that was resistant to anti-Fas-antibody. These findings
      suggest that the interaction of Fas and FAP-1 has a very important role in Fas
      mediated apoptosis signal transduction. The inhibition of the Fas/ FAP-1 binding
      will provide a good target to develop anti-cancer drugs.

PMID- 9030234
TI  - [Apoptosis and chemosensitivity].
AB  - Many antineoplastic drugs and cytotoxic irradiation induce apoptosis in cancer
      cells. ICE and ICE-like proteases play important roles in drug-induced apoptosis
      of cancer cells. We evaluated the cellular factors affecting susceptibility to
      apoptosis using gene-transfected cells. Introduction of bcl 2 gene into human
      small cell lung cancer cells conferred resistance to mitomycin C and irinotecan.
      DNA fragmentation was reduced in these cells. These results indicate apoptosis is
      one of the mechanisms of cell death caused by some antineoplastic drugs.
      Investigations are ongoing to elucidate the contribution of the Bcl 2 family
      proteins to antineoplastic drug induced apoptosis. Wild type p53-transfected
      cancer cells were sensitive to anticancer drugs. On the other hand, p53-depleted
      cells were reported to be more sensitive to taxanes than p53-proficient cells.
      Introduction of Rb gene and p16-gene enhanced cytotoxicity of taxanes and
      topoisomerase I inhibitors, respectively. In clinical studies, patients of non
      small cell lung cancer with high expression of Bcl-2 were reported to show longer
      survival than patients with lower expression. However, this result may be
      confusing because Bcl-2 reduced the efficacy of antineoplastic drugs. Further
      evaluation is required to determine the cellular proteins serving as markers for
      treatment efficacy or prognosis.

PMID- 9030236
TI  - [Our policy and future tasks related to ICH in anti-cancer drug development--a
      discussion from the viewpoint of an enterprise].
AB  - International harmonization of data to be submitted in order to receive
      governmental authorization for the release of new medicines (ICH) has been
      promoted by Japan, the USA and European countries. Because of this trend, the
      Japanese drug authority, the medical institutions which perform clinical trials
      of not yet authorized new drugs and the pharmaceutical companies which contract
      these trials to medical institutions, are now required to change greatly their
      conventional views concerning drug development. The trend towards ICH has also
      been having a great impact on the development of anti-cancer agents in Japan. The
      greatest impact of ICH is that it requires pharmaceutical companies to take
      responsibility for the planning, pursuit and management of clinical trials of new
      drugs. To meet this requirement, it is urgent that pharmaceutical companies
      educate and train staff members involved in drug development, so that they attain
      high levels of medical proficiency in the field concerned. It is also necessary
      for these companies to organize in house groups of specialists in making clinical
      trials, who can evaluate clinical data and make decisions about outcomes by
      themselves. At the same time, medical institutions are required to establish a
      system which supports the clinical trials carried out within the hospital, while
      meeting the appropriate guidelines. Thus, medical institutions are required to
      make greater efforts to ensure adequate disclosure of diagnosis of cancer to a
      patient, obtain informed consent from patients and develop a hospital system
      capable of conducting excellent clinical trials. The governmental authority
      related to drugs is required to improve drug administration, including
      streamlining regulations and providing consultation services concerning the
      appropriate strategy for particular clinical trials. If the relevant governmental
      authority, medical institutions, pharmaceutical companies and mass media
      cooperate with the goal of improving the environment and systems related to
      clinical trials, the current system of clinical trials will be improved
      significantly, allowing more scientific and ethical clinical trials. This, in
      turn, will promote the smoother development of anti cancer agents in this
      country. At present, both the views on and the manner of conducting clinical
      trials (especially phase I clinical trials) differ in Japan and Western
      countries. These differences cause differences in the scheduling of preclinical
      studies, possibly leading to delayed commencement of phase I clinical trials in
      Japan. Among these issues, the procedures for preclinical studies of safety and
      pharmacokinetics studies (absorption, distribution, metabolism and elimination of
      drugs) need to be internationally standardized as soon as possible.

PMID- 9030237
TI  - [What has been done for international harmonization and what remains to be
      solved?].
AB  - With the idea of expediting drug development and increasing the availability of
      new medicines to patients, the International Conference on Harmonization (ICH)
      was organized more than five years ago. Since then, significant progress has been
      made toward harmonizing preclinical and clinical requirements for the development
      of medicinal products. For companies whose drug development strategy is global
      and ongoing in different countries, international harmonization has been an
      important subject for R&D strategy as well as a critical target that must be
      achieved. Rhone-Poulenc Rorer, a multi national pharmaceutical company, has
      globally developed an anti cancer drug, docetaxel, in midstream of international
      harmonization efforts, and faced various difficulties related to international
      harmonization. In this paper, based on the author's preclinical experience
      obtained from the development of docetaxel, various approaches in addressing ICH
      related difficulties/problems and pending issues are described. In conclusion,
      the author acknowledges that ICH has made a significant achievement in
      harmonizing the requirements in certain areas of drug development. However, it
      seems that even a joint effort of ICH participants, pharmaceutical industry and
      regulatory agencies may not be enough to address social difficulties associated
      with drug development rather than scientific discipline. Among many other classes
      of drugs, the relationship with society appears to be most complicated in anti
      cancer drug development, specifically at the clinical level, in which cancer
      patients are recruited for Phase I study. Finally, as a future target of ICH,
      harmonization efforts on the way NDA dossiers are appraised and processed across
      tri-partite regulatory authorities is of great interest for international
      pharmaceutical enterprises.

PMID- 9030238
TI  - [Introduction of anticancer agents to phase I clinical trials].
AB  - Because about half of patients with cancer could not be cured by the present
      standard therapy, new effective anticancer agents should be developed and
      introduced at the clinical level. However, there are several important and
      specific issues from scientific, medical, statistical, and ethical viewpoints in
      the design and conducting of phase I clinical trials of new anticancer agents.
      Clinical safety data management is critically important in phase I clinical
      trials. Phase I clinical trials are vastly different from phase II or III
      clinical trials in terms of these issues. This paper discusses issues of early
      anticancer drug development to be solved or improved.

PMID- 9030239
TI  - Potential role of platelets and coagulation factors in the metastasis of
      prostatic cancer.
AB  - One of the common surgical procedures used in the management of prostate cancer
      is transurethral resection of the prostate in which the possibility of the escape
      of tumor cells and their encounter with the hemostatic system is reported to
      contribute to the threat of hematogenous dissemination. We are reporting about
      the role of the hemostatic system involving the platelets and coagulation factors
      in the dissemination process in a tumor model carrying Dunning's R3327 AT3
      adenocarcinoma of the prostate whose metastatic behavior is similar to that of
      human prostatic cancer. Our data revealed that the number of circulating
      platelets dropped and their aggregation activity increased in tumor-bearing rats
      as compared to controls. Normal platelets when treated with tumor effusions and
      reacted with the exogenous aggregating agent collagen exhibited a significant
      increase in the aggregating activity suggesting that the tumor and its
      microenvironment were capable of activating the hemostatic system. Out of eight
      coagulation factors measured only factors XI and XII were significantly decreased
      in tumor-bearing rats. The role of platelets in the metastatic process is
      discussed.

PMID- 9030240
TI  - Verapamil inhibits to different extents agonist-induced Ca2+ transients in human
      tumor cells and in vitro tumor cell growth.
AB  - Platelet agonists are known to contribute to the regulation of cytoplasmic Ca2+
      levels in tumor cells and this property could be relevant in the stimulation of
      cell proliferation. In the present study we investigated the ability of ADP,
      collagen and thrombin to increase cytoplasmic Ca2+ levels in different human
      tumor cell lines (mesothelioma, DND-1A melanoma, HeLa uterine carcinoma) and we
      analyzed the effect of the calcium channel blocker verapamil on Ca2+ fluxes and
      on in vitro tumor cell growth. ADP was able to induce a transient increase in the
      cytoplasmic Ca2+ concentration in tumor cells from all lines; collagen showed
      this effect in mesothelioma cells and in HeLa cells, and thrombin was effective
      only in mesothelioma cells. Verapamil inhibited Ca2+ fluxes induced by the
      effective agonists in a dose-dependent manner. Values of IC50 for inhibition of
      ADP-induced Ca2+ transients were 63.5 microM in mesothelioma cells, 97.3 microM
      in DND-1A cells and 93.5 microM in HeLa cells, while those for inhibition of
      collagen-induced Ca2+ movements were slightly higher (170.2 microM in
      mesothelioma cells and 112.3 microM in HeLa cells) and the value of IC50 for
      inhibition of thrombin-induced Ca2+ fluxes (evaluated only in mesothelioma cells)
      was lower (22.5 microM). The drug dose-dependently also inhibited the in vitro
      growth of tumor cells; values of IC50 for growth inhibition were 21.8 microM in
      mesothelioma cells, 9.1 microM in DND-1A cells and 6.4 microM in HeLa cells,
      suggesting that the antiproliferative activity of verapamil was partly Ca(2+)
      independent. These data may be of interest to elucidate the mechanisms of the two
      way interactions of tumors with the hemostatic system and may help to identify
      new pharmacologic strategies for their control.

PMID- 9030241
TI  - Exposure to vinblastine modulates beta 1 integrin expression and in vitro binding
      to extracellular matrix molecules in a human renal carcinoma cell line.
AB  - Solitary stroma-invading tumor cells expressing the ATP-binding cassette
      transporter P-glycoprotein have been reported to be associated with a
      significantly higher incidence of vessel invasion and lymph node metastases. In
      contrast to P-gp-mediated multidrug resistance (MDR) which has become well
      characterized over the last decade, little is known about further morphological
      and functional alterations in drug-resistant tumor cells. Binding of malignant
      cells to components of the extracellular matrix mediated by beta 1 integrins has
      been suggested to play a substantial role in the metastatic cascade. We studied
      alterations of beta 1 integrin expression and in vitro adhesiveness to
      extracellular matrix proteins of the human renal carcinoma line Caki-1 in
      comparison to the vinblastine resistant sublines Caki-1/V1 and Caki-1/V10
      (cultured in the presence of 1 ng/ml and 10 ng/ml vinblastine, respectively).
      Both VLA-1 and VLA-2 receptors were acquired by the Caki-1/V10 subline, whereas
      untreated and Caki-1/VI cells lacked surface expression of these antigens. VLA-6
      was found to be decreased in the vinblastine-resistant sublines. Attachment of
      drug-resistant Caki-1/V1 and Caki-1/V10 cells to collagen type I was
      significantly increased when compared to parental cells (p < or = 0.005).
      Significant differences in the attachment to type IV collagen were observed
      between Caki-1/V10 and untreated cells (p < or = 0.045). Both Caki-1/V1 and Caki
      1/ V10 cells exhibited increased adhesion to fibronectin when compared to cells
      of the untreated line (p < or = 0.04). Whether an aberrant expression of beta 1
      integrin receptors in resistant cells in combination with altered tumor cell
      adhesiveness is caused by MDR induction or whether it is an epiphenomenon of
      cytotoxic stress is unknown. Future studies will be needed to characterize the
      clinical relevance of MDR-associated changes in tumor cells.

PMID- 9030242
TI  - Inhibition of lymphatic metastasis in a syngeneic rat fibrosarcoma model by an
      angiogenesis inhibitor, AGM-1470.
AB  - We examined whether lymphatic metastasis was inhibited by the potent angiogenesis
      inhibitor AGM-1470 [O-(chloroacetyl-carbamoyl)fumagillol, TNP-470] using a rat
      lymphatic metastasis model. Clone A of the rat fibrosarcoma AS653HM, when
      inoculated into the footpads of syngeneic rats, highly and preferentially
      metastasized to lymph nodes. In contrast, when AGM-1470 was administered
      subcutaneously to rats bearing the tumor cells, the tumor growth and incidence of
      metastasis in the lymph nodes were reduced in a dose- and schedule-dependent
      manner. Similar inhibition of lymphatic metastasis was also observed in the rats
      in which treatment with AGM-1470 was initiated following resection of the primary
      tumor in the foot, indicating that the treatment with AGM-1470 inhibited the
      progression of lymphatic metastasis at the metastatic sites of the lymph nodes.
      These results suggest that AGM-1470 can be a potential agent to prevent lymphatic
      metastasis.

PMID- 9030243
TI  - Metastatic human rhabdomyosarcoma: molecular, cellular and cytogenetic analysis
      of a novel cellular model.
AB  - A new human metastatic rhabdomyosarcoma (RMS) model was established and analyzed
      for a number of biologic, cytogenetic and molecular parameters. Consistent with
      previous studies, the metastatic capacity of different RMS cell variants did not
      correlate with their tumorigenic or proliferative capacities. Interestingly, a
      highly metastatic variant was diploid, while a nonmetastatic variant was
      tetraploid, which parallels previous clinical observations. Genes whose
      expression had been found to be associated with either low- or high-metastatic
      capacity in carcinoma or melanoma did not show a similar association with
      different metastatic variants of RMS, derived from a mesenchymal tumor. We also
      found, in transient reporter gene assays, that several promoters had higher
      transcriptional activity in highly metastatic than in nonmetastatic RMS cell
      variants. This novel human RMS metastatic model may be instrumental for a better
      understanding of the regulatory pathways that control the metastatic phenotype of
      tumors of mesenchymal origin.

PMID- 9030244
TI  - Suppression of metastatic potential of high-metastatic Lewis lung carcinoma cells
      by vanadate, an inhibitor of tyrosine phosphatase, through inhibiting cell
      substrate adhesion.
AB  - Treatment of high-metastatic Lewis lung carcinoma A11 cells with sodium
      orthovanadate, a phosphotyrosine phosphatase inhibitor, resulted in a dose- and
      time-dependent suppression of cell spreading on various extracellular matrix
      components such as Matrigel, fibronectin, laminin and type IV collagen, while the
      treatment did not significantly inhibit attachment of the cells to these
      substrates. Orthovanadate slightly and reversibly inhibited the in vitro cell
      growth of A11 cells, but the suppression of cell spreading was not directly due
      to the inhibition of cell growth. Orthovanadate-treated A11 cells showed reduced
      invasive ability in a reconstituted basement membrane invasion assay and
      experimental metastatic ability. Protein tyrosine phosphorylation level in A11
      cells was elevated after treatment with orthovanadate. The increase in tyrosine
      phosphorylation level was partially diminished by the tyrosine kinase inhibitor
      ST638, concomitantly with restoration of the suppressed cell spreading as well as
      invasive and metastatic abilities. These results suggest that protein tyrosine
      phosphorylation influences invasive and metastatic potential of tumor cells
      possibly through regulating cell-substrate adhesion.

PMID- 9030245
TI  - Identification of an autocrine mechanism for regulating cell-cycle progression in
      murine keratinocytes.
AB  - Primary murine keratinocytes possess a limited doubling potential regardless of
      plating density or the inclusion of competence factors insulin, epidermal growth
      factor, and/or fetal bovine serum within the culture medium. In contrast, a
      murine cell line (CH-72), derived from a 7,12-dimethylbenz[a]
      anthraceneinitiated, 12-O-tetra-decanoylphorbol-13-acetate-promoted mouse skin
      carcinoma, was found to exhibit unlimited proliferative potential; this was
      demonstrated by the ability of these cells to produce the progression factor
      required for entry into the DNA-synthesis phase in the absence of competence
      factor stimulation. Conditioned medium, collected from murine carcinoma cells,
      was subsequently shown to increase the level of [3H]thymidine incorporation in
      competence-factor-deprived CH-72 cultures by more than a factor of 4 within 16 h.
      Moreover, consistent with its ability of recruit cells cycling within the first
      gap phase directly into the DNA-synthesis phase, the autocrine progression factor
      present in conditioned medium decreased the G1:S ratio from the 55:29 observed
      with growth medium controls to 38:46. Preliminary characterization of the
      autocrine factor produced by cultured murine carcinoma cells using gel-filtration
      chromatography revealed a molecular mass of less than 2 kDa, similar in size to
      the factor previously shown by our laboratory to promote G1-phase progression in
      cultures of normal human foreskin keratinocytes.

PMID- 9030246
TI  - A new cell line from human undifferentiated carcinoma of the ovary: establishment
      and characterization.
AB  - A cell line designated CUMO-2 has been established from an undifferentiated
      ovarian carcinoma. The s.c. injection of cells into nude mice gave rise to fast
      growing tumors, while the i.p. route induced a peritoneal carcinomatosis with
      ascites. Histopathologically, the transplanted s.c. tumors closely resembled the
      original tumor, but tumors developed in the peritoneal cavity were highly
      anaplastic. The epithelial nature of the cells was confirmed by ultrastructural
      analysis. Sequential cytogenetic analyses on early and late passages revealed
      highly aneuploid tumor cells with consistent structural aberrations of
      chromosomes 1, 3, 8 and 11. CUMO-2 cells were found to produce CA 125 in vitro
      and in vivo. Cytosol estrogen receptor (ER) was found but progesterone receptor
      (PR) was not measured. HLA typing indicated the presence of DR8 and DQw4. A
      gonadotropin-releasing hormone (Gn-RH) analog inhibited cell growth and Gn-RH
      receptor mRNA was detected by reverse transcription/polymerase chain reaction in
      this cell line. Administration of transforming growth factor beta 1 inhibited
      both cell growth and c-myc mRNA expression. This cell line demonstrated a
      conformational band shift in exon 7 of the p53 gene. It was a frameshift
      mutation.

PMID- 9030247
TI  - A ribozyme specifically suppresses transformation and tumorigenicity of Ha-ras
      oncogene-transformed NIH/3T3 cell lines.
AB  - In this study, the efficacy of an anti-ras ribozyme in reversing a transformed
      phenotype was investigated. A murine NIH/3T3-derived cell line, designated 2-12,
      contains an inducible Ha-ras oncogene, which is regulated by the Escherichia coli
      (E. coli) lac operator/repressor system, and displays a transformed phenotype
      after isopropyl-beta-D-thiogalactoside induction. To reverse the transformed
      characteristics, the ribozyme, which specifically targets the Ha-ras oncogene at
      the codon 12 mutation site (GGC to GUC), was transfected into 2-12 cells. Two
      (ribZ4 and ribZ7) clones were subsequently selected and analyzed for their
      transforming features. Our results show that, in the transfectants, ribozyme gene
      expression was detected, and the target Ha-ras transgene was expressed at basal
      levels. Their phenotypic responses, including morphology, cell growth rate,
      colony-formation efficiency and tumorigenicity in mice with severe combined
      immunodeficiency were more similar to those of NIH/3T3 than 2-12 transformed
      cells. Directly injecting the ribozyme DNA into tumors induced by transformed 2
      12 cells in BALB/c mice also caused tumor regression. The enzymatic cleavage
      products of the ribozyme acting on mutant Ha-ras mRNA in vivo were detected by
      primer-extension analysis. These results indicate that the ribozyme were designed
      exhibits a site-specific ribonuclease function that effectively abrogates Ha-ras
      oncogene-induced transformation, and this unique anti-Ha-ras property should shed
      light on the development of strategies against the Ha-ras-oncogene-initiated
      malignancy.

PMID- 9030248
TI  - Unstimulated human acute myelogenous leukemia blasts secrete matrix
      metalloproteinases.
AB  - PURPOSE: The secretion of metalloproteinases was examined, especially the 92-kDa
      and 72-kDa type IV collagenases/gelatinases, and their role in the degradation of
      reconstituted basement membrane (Matrigel) by leukemic blasts. METHODS AND
      RESULTS: Leukemic blasts were obtained from the peripheral blood of 11 patients
      diagnosed with acute myelogenous leukemia (AML). After incubation of the AML
      blasts in serum-free cultures, conditioned media were collected and examined by
      zymography. The 92-kDa gelatinase was detected in ten AML patients after 2 h and
      24 h of incubation, and in five samples its activated form (83 kDa) was observed.
      72-kDa gelatinase was detected in cell-conditioned media from four patients after
      2 h and in media from ten patients after 24 h. Its activated forms (64-60 kDa)
      were observed in one of four samples after 2 h and in five of ten after 24 h. By
      contrast, normal peripheral mononuclear cells from healthy donors secreted only
      92-kDa gelatinase after 24 h; the 72 kDa enzyme was not detectable. A specific
      inhibitor of metalloproteinases, 1,10-phenanthroline, significantly reduced the
      in vitro invasion of AML blasts in a Matrigel assay and completely inhibited
      gelatinolytic activity in zymography. CONCLUSIONS: We concluded that primary,
      unstimulated peripheral-blood AML blasts secrete metalloproteinases, which may
      contribute to the in vitro degradation of reconstituted basement membrane.

PMID- 9030250
TI  - Combined effects of epirubicin and tamoxifen on the cell-cycle phases in estrogen
      receptor-negative Ehrlich ascites tumor cells.
AB  - Laboratory and clinical data suggest some interactions between cytotoxic agents
      and tamoxifen. The mechanisms of these interactions differ in estrogen-receptor
      negative cell lines. The ability of tamoxifen to modify the effects of epirubicin
      on the cell-cycle phases of estrogen-receptor-negative Ehrlich's carcinoma
      ascitic cells (EATC) was studied in mice. The results showed that combination of
      tamoxifen with epirubicin decreased the thymidine labelling index more
      effectively than did either drug alone. Adding tamoxifen to epirubicin treatment
      induced both an early S-phase and G2-M-phase arrest and a later G0-G1-phase
      arrest in EATC. An increase of S0 cells in the quiescent fraction could play a
      role in these changes, and some of these quiescent cells may not be viable,
      causing them to die later. In conclusion, the data suggest that continuous
      exposure to tamoxifen might modify the effects of epirubicin via cell-cycle
      perturbations.

PMID- 9030249
TI  - Nerve growth factor stimulates in vitro invasive capacity of DU145 human
      prostatic cancer cells.
AB  - The prevalence of nerve growth factor (NGF) production in different human
      prostatic tumor cell lines (DU145, PC-3, LNCaP-FGC) was investigated using a
      specific enzyme-linked immunosorbent assay (ELISA) and compared to that of
      different human and rat prostatic tissue samples. In addition, the biological
      effects of NGF beta addition to the human prostatic cancer cell cultures were
      investigated. The ELISA technique showed the DU145 cell line to secrete
      measurable levels of NGF in the culture medium. When neurite-outgrowth
      determination in a pheochromocytoma cell line was used as a bioassay, the NGF
      synthesized by DU145 cells was confirmed to exhibit functional biological
      activity. No effect of exogenously added NGF could be established on tumor cell
      proliferation, on the basis of either colorimetric tetrazolium-based staining
      assay or bromodeoxyuridine incorporation. Also the expression of prostate
      specific acid phosphatase was not influenced by NGF addition. However, the in
      vitro invasive capacity (Matrigel) of DU145 cells was significantly increased by
      inclusion of 50 ng or 100 ng NGF beta/ml culture medium. In view of the
      clinically well-known perineural invasion of prostate cancer cells, the possible
      involvement of NGF as a (paracrine) factor in prostatic cancer metastatic
      behavior should be investigated further.

PMID- 9030251
TI  - WAF1 expression and p53 mutations in human colorectal cancers.
AB  - The expression of the WAF1 gene was examined in the tissues of primary colorectal
      cancers and of adjacent non-neoplastic mucosas by Western blot analysis. p53
      mutations of these cancer tissues were also analyzed by the polymerase chain
      reaction/single-strand conformation polymorphism followed by direct sequencing.
      Missense mutations of p53 were recognized in 19 out of 40 cases. Five cancers
      (12.5%) displayed much lower expression of WAF1 than did their corresponding
      mucosas, and all of them contained mutant p53. Fourteen cancers (35%) expressed
      the same level of WAF1 as their mucosas, and 5 of them had mutant p53. Twenty-one
      cancers (52.5%) had much higher WAF1 expression than their mucosas, and 9 of them
      had mutant p53. When Duke's classification was applied to these colorectal
      cancers, it was found that the cancers with reduced expression of WAF1 basically
      coincided with late (C or D) stages (4 out of 5 cases), while the cancers with
      higher WAF1 expression were consistent with early (A or B) stages (17 out of 21
      cases). Down-regulation of WAF1 in colorectal cancer tissues may be implicated in
      tumor progression.

PMID- 9030252
TI  - Overexpression of cyclin B1 in human colorectal cancers.
AB  - The expression of the human cyclin B1 gene was investigated with Western blot
      analysis in human colorectal carcinomas and in adjacent non-neoplastic colorectal
      mucosas. Out of 41 cancers, 36 (88% of patients) showed much higher expression of
      cyclin B1 than did the non-neoplastic mucosa. Proliferating-cell nuclear antigen
      (PCNA) immunohistochemistry revealed that the labeling indexes of these cancer
      tissues were 47.3 +/- 11.3% while those of the mucosa were 15.6 +/- 5.5%. Only 5
      cancers (12% patients) demonstrated the same expression level of cyclin B1 as the
      mucosa; however, the PCNA labeling indexes were 42.3 +/- 11% for the cancer
      tissue, compared to 12.6 +/- 2.4% for the mucosas. Southern blot analysis showed
      that there was no change of the cyclin B1 gene at the somatic DNA level in spite
      of its high expression at the protein level. These results proved that majority
      of colorectal cancers express high levels of cyclin B1, consistent with a high
      rate of cell proliferation, whereas a small fraction of these cancers lose
      control of cyclin B1 expression, diverging from their fast cell proliferation.

PMID- 9030253
TI  - The correlation of CA15.3 and TPS with tumor course in patients with metastatic
      breast cancer.
AB  - PURPOSE: This study was performed to determine the correlation of CA15.3 and TPS
      with disease course in patients with metastatic breast cancer. METHODS: Levels of
      CA15.3 and tissue polypeptide antigen using the M3 monoclonal antibody (TPS) were
      determined in the serum of 60 patients with metastatic breast cancer. CA15.3 and
      TPS were measured at two assay times. RESULTS: A change of more than 25% in the
      serum level of CA15.3 or TPS was highly correlated with tumor response. The
      association between response and change in marker levels was stronger for CA15.3
      (P = 0.0001) than for TPS (P = 0.0005). Distinct mismatches between marker
      changes and the tumor response were observed for both CA15.3 and TPS. CONCLUSION:
      CA15.3 and TPS are useful in the determination of response to treatment. Because
      of observed disagreement, marker changes can only be regarded as indicative of
      disease course.

PMID- 9030254
TI  - Primary sodium ion translocating enzymes.

PMID- 9030255
TI  - Ca2+ transport by the sarcoplasmic reticulum ATPase.

PMID- 9030256
TI  - What is the driving force for protein import into mitochondria?
AB  - Nuclear-encoded mitochondrial proteins are synthesized in the cytosol as
      precursors and then imported into mitochondria. Protein import into the matrix
      space requires the function of the mitochondrial hsp70 (mhsp70) chaperone. mhsp70
      is an ATPase that acts in conjunction with two partner proteins: the Tim44
      subunit of the inner membrane import complex, and the nucleotide exchange factor
      mGrpE. A central question concerns how mhsp70 uses the energy of ATP hydrolysis
      to transport precursor proteins into the matrix. Recent evidence suggests that
      mhsp70 is a mechanochemical enzyme that actively pulls precursors across the
      inner membrane.

PMID- 9030257
TI  - Proton-translocation by membrane-bound NADH:ubiquinone-oxidoreductase (complex I)
      through redox-gated ligand conduction.
AB  - For the catalytic mechanism of proton-translocating NADH-dehydrogenase (complex
      I, EC 1.6.99.3) a number of hypothetical models have been proposed over the last
      three decades. These models are discussed in the light of recent substantial
      progress on the structure and function of this very complicated multiprotein
      complex. Only the high-potential iron-sulfur center N-2 and ubiquinone seem to
      contribute to the proton-translocating machinery of complex I: Based on the pH
      dependent midpoint potential of iron-sulfur cluster N-2 and the physical
      properties of ubiquinone intermediates a novel mechanism is proposed. The model
      builds on a series of defined chemical reactions taking place at three different
      ubiquinone-binding sites. Therefore, some aspects of this redox-gated ligand
      conduction mechanism are reminiscent to the proton-motive Q-cycle. However, its
      central feature is the abstraction of a proton from ubihydroquinone by a redox
      Bohr group associated with iron-sulfur cluster N-2. Thus, in the proposed
      mechanism proton translocation is driven by a direct linkage between redox
      dependent protonation of iron-sulfur cluster N-2 and the redox chemistry of
      ubiquinone.

PMID- 9030258
TI  - Bovine-heart NADH:ubiquinone oxidoreductase is a monomer with 8 Fe-S clusters and
      2 FMN groups.
AB  - The availability of the amino-acid sequences of a number of mitochondrial and
      bacterial NADH:ubiquinone oxidoreductases (Complex I), the sequence similarities
      of five of the essential subunits of Complex I with subunits of
      [NiFe]hydrogenases and [Fe]hydrogenases, as well as some long-standing
      controversies about the precise EPR properties and stoichiometries of the iron
      sulfur clusters in Complex I have led us to propose a new structural and
      functional model for this complicated enzyme. The functional unit is a monomer
      comprising 8 different Fe-S clusters and 2 FMN molecules as prosthetic groups.
      The electron-input pathway, as well as part of the electron-transfer components,
      seem largely inherited from bacterial NAD(+)-reducing hydrogenases. The essential
      electron-transfer components of the electron-output pathway are located in the
      TYKY subunit. This subunit is proposed to hold both iron-sulfur clusters 2 and to
      render the enzyme the ability to perform coupled electron transfer. Based on
      earlier observed similarities (Albracht. S.P.J. (1993) Biochim. Biophys. Acta
      1144, 221-224) of the 49 kDa subunit and the PSST subunit with, respectively, the
      large and small subunits of [NiFe]hydrogenases, it is proposed that the 49
      kDa/PSST subunit couple provides Complex I with an ancient proton-transfer
      pathway.

PMID- 9030259
TI  - FSBA modifies both alpha- and beta-subunits of F1 specifically and can be bound
      together with AXP at the same alpha-subunit.
AB  - Binding of 1 mole 5'-fluorosulfonylbenzoyladenosine (FSBA) per mol F1 induces
      about 50% inhibition of ATPase activity and 80% inhibition of ITPase activity.
      The binding of additional ligand results in a further inhibition of both
      activities. Maximally 5 mol/mol F1, causing complete inhibition of activity, can
      be bound. Using radioactive FSBA more label is found on alpha-subunits than on
      beta-subunits under the usual buffer conditions. The modified amino acids are
      alpha-Tyr300, alpha-Tyr244 and beta-Tyr368. Binding of FSBA, at least up to 3
      mol/mol F1, does not result in loss of bound ADP, whether the starting enzyme
      contains 2, 3 or 4 bound nucleotides. Added adenine nucleotides compete with FSBA
      only for binding that results in modification of beta-subunits, shifting the
      alpha/beta ratio of bound label to higher values. It is concluded that the alpha
      subunits contain two hydrophobic pockets for the binding of nucleoside moieties,
      with a different orientation relative to the P-loop. One pocket contains alpha
      Tyr244 and alpha-Tyr300, the other beta-Tyr368. Since, however, in the binding of
      adenine nucleotide di- or triphosphates the P-loop is involved, only one of these
      ligands can bind per subunit. The previously not understood binding
      characteristics of several substrate analogues have now become interpretable on
      the assumption that also the structurally homologous beta-subunits contain 2
      pockets where nucleoside moieties can bind. The kinetic effects of FSBA binding
      indicate that the first FSBA binds at the regulatory site that has a high
      affinity for ADP and pyrophosphate. Binding of pyrophosphate at this high
      affinity regulatory site increases the Vmax of the enzyme, while binding at a
      second regulatory site, a low-affinity site, increases the rate of binding of
      FSBA with a factor of about 3. Binding of bicarbonate at this latter site is
      responsible for the disappearance of the apparent negative cooperativity of the
      ATPase activity.

PMID- 9030260
TI  - Modification of membrane-bound F1 by p-fluorosulfonylbenzoyl-5'-adenosine: sites
      of binding and effect on activity.
AB  - Bovine heart submitochondrial particles (smp) were incubated with p
      fluorosulfonylbenzoyl-5'-adenosine (FSBA) in order to study the binding of this
      ligand and its effect on ATP synthesis and ATP hydrolysis in smp and to compare
      the results with those obtained with isolated F1. The binding was measured with
      the 14C-labeled compound. ATP hydrolysis was in all cases as much inhibited as
      succinate-driven ATP synthesis and ITP hydrolysis was more inhibited than ATP
      hydrolysis. The binding experiments show that modification of three nucleotide
      binding sites results in nearly complete inhibition of ATPase activity. In the
      presence of pyrophosphate up to 6 mol [14C]SBA/mol F1 can be bound. FSBA
      preferentially modifies amino acids of the alpha-subunits but also beta-subunits
      are modified. It is concluded that modification of both subunits results in
      inhibition of activity. The results are very well comparable with the results
      obtained with isolated F1, which indicates that our preparation of F1 is a good
      model for F1 in the intact system. Furthermore it is concluded that each alpha
      subunit of F1 in smp, just like in the isolated form, contains two pockets where
      adenosine moieties can bind, one located above the P-loop, modifying alpha-Tyr
      244 and alpha-Tyr-300 and the other one located below the P-loop where also the
      adenosine moiety of AD(T)P binds, modifying beta-Tyr-368.

PMID- 9030261
TI  - 6-Ketocholestanol is a recoupler for mitochondria, chromatophores and cytochrome
      oxidase proteoliposomes.
AB  - The effect of 6-ketocholestanol (kCh) on various natural and reconstituted
      membrane systems has been studied. 6-ketocholestanol (5 alpha-Cholestan-3 beta-ol
      6-one), a compound increasing the membrane dipole potential, completely prevents
      or reverses the uncoupling action of low concentrations of the most potent
      artificial protonophore SF6847. This effect can be shown in the rat liver and
      heart muscle mitochondria, in the intact lymphocytes, in the Rhodobacter
      sphaeroides chromatophores, and in proteoliposomes with the heart muscle or Rh.
      sphaeroides cytochrome oxidase. The recoupling effect of kCh disappears within a
      few minutes after the kCh addition and cannot be observed at all at high SF6847
      concentrations. Almost complete recoupling is also shown with FCCP, CCCP, CCP and
      platanetin. With 2,4-dinitrophenol, fatty acids and gramicidin, kCh is
      ineffective. With TTFB, PCP, dicoumarol, and zearalenone, low kCh concentrations
      are ineffective, whereas its high concentrations recouple but partially. The kCh
      recoupling is more pronounced in mitochondria, lymphocytes and proteoliposomes
      than in chromatophores. On the other hand, mitochondria, lymphocytes and
      proteoliposomes are much more sensitive to SF6847 than chromatophores. A
      measurable lowering of the electric resistance of a planar bilayer phospholipid
      membrane (BLM) are shown to occur at SF6847 concentrations which are even higher
      than in chromatophores. In BLMs, kCh not only fails to reverse the effect of
      SF6847, but even enhances the conductivity increase caused by this uncoupler. It
      is assumed that action of low concentrations of the SF6847-like uncouplers on
      coupling membranes involves cytochrome oxidase and perhaps some other membrane
      protein(s) as well. This involvement is inhibited by the asymmetric increase in
      the membrane dipole potential, caused by incorporation of kCh to the outer
      leaflet of the membrane.

PMID- 9030262
TI  - Regulation of the energy coupling in mitochondria by some steroid and thyroid
      hormones.
AB  - Male sex hormones [dihydrotestosterone (DTS), and testosterone] and progesterone,
      when added to the isolated rat liver mitochondria before or after some
      protonophores, lower the respiration rate and increase the delta psi level, i.e.,
      reverse the protonophore-induced uncoupling. Such a recoupling ability shows
      specific structural requirements correlating with hormonal activity of steroids
      studied. For instance, epiandrosterone, a DTS isomer of very low hormonal
      activity, and deoxycorticosterone, differing from progesterone by additional OH
      group and possessing quite different hormonal activity, as well as female sex
      hormones (estron and estradiol) show no recoupling effect. Like 6-ketocholestanol
      (kCh), male sex hormones and progesterone recouple mitochondria uncoupled by low
      concentrations of SF6847, FCCP and CCCP, but not by high concentration of these
      uncouplers or by any concentration of DNP, palmitate and gramicidin. In contrast
      to recoupling by kCh, hormonal recoupling requires addition of serum albumin and
      is inhibited by low concentrations of palmitate. Recoupling can also be shown on
      the heart and skeletal muscle mitochondria, being absent from the heart muscle
      submitochondrial particles, the bacterial chromatophores and the cytochrome
      oxidase proteoliposomes. In mitochondria it does not depend upon the oxidation
      substrate used (succinate or PMS + ascorbate were tested). Pronounced seasonal
      effect upon the DTS recoupling degree was revealed. The recoupling is maximal in
      January, February and from June to November, being minimal in the spring months
      and in December. In spring, the in vivo administration of thyroxine, di- or
      triiodothyronine improves the recoupling ability of DTS. 2 x 10 - 6 M. Thyroxine,
      when added in vitro, does not affect energy coupling if SF6847 was absent. In the
      presence of small amounts of SF6847, thyroxine stimulates the uncoupling in a DTS
      sensitive fashion, di- and triiodothyronines being less effective. Addition of
      thyroxine to azide-inhibited mitochondria (oligomycin is present) stimulates
      respiration and normalizes the delta psi level. In this system, triiodothyronine
      is much less effective, whereas diiodothyronine is not effective at all. In the
      intact cells (thymocytes and the Krebs-II cells were tested), DTS lowers the
      respiration rate stimulated by low concentrations of SF6846 or FCCP. In this
      case, serum albumin is not required. It is suggested that recoupling effects of
      male sex hormones and progesterone are involved in their anabolic action just as
      uncoupling takes part in the catabolic activity of thyroid hormones.

PMID- 9030263
TI  - Cell swelling and glycogen metabolism in hepatocytes from fasted rats.
AB  - Cell swelling is known to increase net glycogen production from glucose in
      hepatocytes from fasted rats by activating glycogen synthase. Since both active
      glycogen synthase and phosphorylase are present in hepatocytes, suppression of
      flux through phosphorylase may also contribute to the net increase in glycogen
      synthesis by cell swelling. We have developed an isotopic procedure to estimate
      the fluxes through glycogen synthase and phosphorylase in intact hepatocytes and
      we have examined the effect of cell swelling on both enzyme fluxes. The following
      observations were made. (1) Hypotonic or glutamine-induced cell swelling
      increased net glycogen production by activating flux through glycogen synthase
      with little effect on phosphorylase flux. Proline, previously shown to increase
      glycogen synthesis more than could be accounted for by its ability to cause cell
      swelling, increased flux through glycogen synthase and inhibited phosphorylase
      flux. (2) Incorporation of [14C]glucose into glycogen preceded complete mixing of
      [14C]glucose with the intracellular pool of UDPglucose. It is concluded that cell
      swelling affects glycogen synthase only and that UDPglucose is compartmentalized.

PMID- 9030264
TI  - Quantitative decrease of human cytochrome c oxidase during development: evidences
      for a post-transcriptional regulation.
AB  - In an earlier study, we showed that cytochrome c oxidase activity, measured in
      mitochondria isolated from human muscular biopsies, decreased steadily and
      substantially between the age of four years and adulthood (P < 0.05), whereas
      complexes I and III activity remained constant. The present study investigates a
      number of possible causes for this change in activity: although there is a drop
      in the apparent Vmax, neither the apparent enzyme Km, nor the cellular mtDNA
      concentration shows any variations over the studied period. Steady-state
      concentrations of mitochondrial gene transcripts (CO I. CO II, CO III, but also
      12S, cytochrome b, or ND4) increase within this age group, indicating an overall
      increase in mitochondrial genome expression. Concentrations of transcripts of
      nuclear genes CO IV, CO Vb, and CO VIaH likewise show an increase, albeit less
      marked. On the other hand, heme aa3 levels and concentrations of mitochondrial
      (CO II) or nuclear (CO IV, CO VIIaH) subunits, estimated using specific
      antibodies, correlate closely with enzymatic activity and show a parallel
      decrease between 4 and 20 years. The observed decrease in complex IV activity is
      thus quantitative, and subject to post-transcriptional and/or post-translational
      regulation.

PMID- 9030265
TI  - Purification and initial kinetic and spectroscopic characterization of NO
      reductase from Paracoccus denitrificans.
AB  - A new and relatively simple procedure to purify NO reductase from Paracoccus
      denitrificans by using the detergent lauryl maltoside has been developed. The
      purified enzyme consists of two subunits according to SDS polyacrylamide gel
      electrophoresis. Analysis of the content of prosthetic groups indicates the
      presence of non-haem iron in addition to the presence b and c cytochromes
      yielding a stoichiometry of haem b/haem c/non-haem iron = 2:1:1. The optical
      spectrum of reduced NO reductase shows bands of low-spin haem c and haem b with
      alpha-band absorbance maxima at 551 nm and 558 nm, respectively. The optical
      spectrum of oxidized NO reductase shows a broad absorbance hand around 590 nm
      which disappears upon reduction. This latter absorbance is ascribed to a high
      spin haem b (charge-transfer) transition. The presence of high-spin haem b is
      also indicated by the shifts observed in the optical spectrum of oxidized NO
      reductase in the presence of NO or in the spectrum of reduced enzyme after
      addition of CO. The main features of the EPR spectrum of the oxidized enzyme are
      resonances from a highly anisotropic low-spin haem b (gz = 3.53) and from an
      anisotropic low-spin haem c with gz, y, x = 2.99, 2.28, 1.46, the two haems being
      present in an approximate 1:1 stoichiometry. Minor signals representing about 1%
      of the enzyme concentration due to high-spin haem b (g = 5.8-6.2) and a novel
      type of signal with g = 2.009 ascribed to high-spin non-haem ferric iron were
      also observed. The analysis of steady-state kinetic measurements of the NO
      reductase activity shows a sigmoidal relation between rate of NO reduction and NO
      concentration, consistent with a model describing sequential binding of two
      molecules of NO to the reduced enzyme. At high NO concentrations substrate
      inhibition occurs (Ki(apparent) = 13.5 microM) suggested to be due to binding of
      NO to oxidized enzyme. The absence from the EPR spectrum of signals originating
      from ferric non-haem iron and ferric high-spin haem b in stoichiometric amounts
      with respect to the enzyme concentration is suggested to be due to an
      antiferromagnetic coupling between these two centers. The steady-state kinetic
      behaviour and the optical and EPR spectroscopic properties of the NO reductase
      are incorporated into a tentative structural and mechanistic model.

PMID- 9030266
TI  - High cyclic transhydrogenase activity catalyzed by expressed and reconstituted
      nucleotide-binding domains of Rhodospirillum rubrum transhydrogenase.
AB  - The hydrophilic, extramembranous domains I (alpha 1 subunit) and III of the
      Rhodospirillum rubrum nicotinamide nucleotide transhydrogenase were expressed in
      Escherichia coli and purified therefrom as soluble proteins. These domains bind
      NAD(H) and NADP(H). respectively, and together they form the enzyme's catalytic
      site. We have demonstrated recently that the isolated domains I and III of the
      bovine transhydrogenase (or domain I of R. rubrum plus domain III of the bovine
      enzyme) reconstitute to catalyze transhydrogenation in the absence of the
      membrane-intercalated domain II, which carries the enzyme's proton channel. Here
      we show that the expressed domains I and III of the R. rubrum transhydrogenase
      catalyze a very high NADP(H)-dependent cyclic transhydrogenation from NADH to
      AcPyAD (3-acetylpyridine adenine dinucleotide) with a Vmax of 214 mumol AcPyAD
      reduced (min x mg of domain I)-1. The reaction mechanism is 'ping-pong' with
      respect to NADH and AcPyAD, as these nucleotides bind interchangeably to domain
      I, and the stereospecificity of hydride ion transfer is from the 4A position of
      NADH to the 4A position of AcPyAD. The expressed domain I is dimeric, like the
      native alpha 1 subunit of the enzyme, but the expressed domain III is monomeric
      and contains 0.94 mol NADP(H) per mol.

PMID- 9030268
TI  - Redox-linked protolytic reactions in soluble cytochrome-c oxidase from beef-heart
      mitochondria: redox Bohr effects.
AB  - A study is presented of co-operative redox-linked protolytic reactions (redox
      Bohr effects) in soluble cytochrome-c oxidase purified from bovine-heart
      mitochondria. Bohr effects were analyzed by direct measurement, with accurate
      spectrophotometric and potentiometric methods, of H+ uptake and release by the
      oxidase associated with reduction and oxidation of hemes a and a3. CuA and CuB in
      the unliganded and in the CN- or CO-liganded enzyme. The results show that there
      are in the bovine oxidase four protolytic groups undergoing reversible pK shifts
      upon oxido-reduction of the electron transfer metals. Two groups with pKox and
      pKred values around 7 and > 12 respectively appear to be linked to redox
      transitions of heme a3. One group with pKox and pKred around 6 and 7 is
      apparently linked to CuB, a fourth one with pKox and pKred of 6 and 9 appears to
      be linked to heme a. The possible nature of the amino acids involved in the redox
      Bohr effects and their role in H+ translocation is discussed.

PMID- 9030267
TI  - Pro- and anti-oxidant activities of the mitochondrial respiratory chain: factors
      influencing NAD(P)H-induced lipid peroxidation.
AB  - This paper is a study of factors influencing the rate of lipid peroxidation in
      beef heart submitochondrial particles induced by NAD(P)H via the NADH-ubiquinone
      oxidoreductase (Complex I) of the respiratory chain. In accordance with earlier
      observations, both NADH and NADPH initiated lipid peroxidation in the presence of
      ADP-Fe3+. The rate of the reaction, measured as oxygen consumption and formation
      of thiobarbituric acid reactive substances, was biphasic as a function of NADH
      concentration, reaching a maximum at low NADH concentrations and then declining.
      In contrast, the NADPH-initiated lipid peroxidation showed a monophasic
      concentration profile of hyperbolic character. Rotenone did not eliminate the
      biphasicity of the NADH-induced reaction, indicating that this was not due to an
      antioxidant effect of reduced ubiquinone at high NADH concentrations. This
      conclusion was further supported by the demonstration that extraction of
      ubiquinone from the particles did not relieve the inhibition of lipid
      peroxidation by high NADH concentrations. However rhein, another inhibitor of
      Complex I, eliminated the biphasicity, and even caused a substantial stimulation
      of the NADH-induced lipid peroxidation in the particles upon extraction of
      ubiquinone by pentane. No similar effect occurred in the case of NADPH-induced
      lipid peroxidation. Furthermore, rhein facilitated both NADH- and NADPH-induced
      lipid peroxidation even in the absence of added ADP-Fe3+, in a fashion similar to
      that earlier reported with succinate in the presence of theonyltrifluoroacetone.
      Based on these findings and measurements of the redox states of ubiquinone and
      cytochromes in the presence of KCN and NADH or NADPH, it is concluded that
      Complex I may distinguish between electron input from NADH and NADPH by
      differences in the site(s) of substrate binding and in the pathways and rates of
      NADH and NADPH oxidation.

PMID- 9030269
TI  - Simultaneous expression of ferredoxin, ferredoxin reductase and P450 in COS7
      cells.
AB  - cDNA fragments encoding mouse ferredoxin and ferredoxin reductase were
      simultaneously introduced into COS7 cells by using an expression vector, pUC-SR
      alpha plasmid. When using the mitochondrial fraction prepared from the
      transfected cells, cytochrome-c reductase activity was detected. This activity
      was highest when 7.5 micrograms of the ferredoxin expression plasmid (pSR alpha
      F) and 2.5 micrograms of the ferredoxin reductase expression plasmid (pSR alpha
      FR) were transfected into COS7 cells. In this system, NADPH could be replaced by
      NADH as a cofactor for the reduction of cytochrome-c although the cytochrome-c
      reductase was more dependent on NADPH than NADH at a low concentration. When
      CYP24 expression plasmid was transfected into COS7 cells along with both pSR
      alpha F and pSR alpha FR, the transfected cells revealed a 3-fold higher 25
      hydroxyvitamin D3-24-hydroxylase activity than COS7 cells transfected with CYP24
      expression plasmid.

PMID- 9030270
TI  - Quinolones and their N-oxides as inhibitors of mitochondrial complexes I and III.
AB  - 4(1H)-quinolones (2-alkyl- (1), 2-alkyl-3-methyl- (2), 2-methyl-3-alkyl- (3), 1
      hydroxy-2-methyl-3-alkyl- (4) and 1-hydroxy-2-alkyl- (5)) with n-alkyl side
      chains varying from C5 to C17 have been synthesized and tested for biological
      activity in mitochondrial complexes. Whereas all quinolones were efficient
      inhibitors of electron transport in the cytochrome b/c1-complex from either beef
      heart or Rhodospirillum rubrum, in complex I from beef heart quinolones 1 and 2
      only were highly active. In a Quantitative Structure-Activity Relationship (QSAR)
      inhibitory activity in the cytochrome b/c1-complexes could be correlated to the
      physicochemical parameters lipophilicity pi and/or to STERIMOL L. Maximal
      inhibitory potency was achieved at a carbon chain length of 12-14 A. Oxidant
      induced reduction of cytochrome b established that some quinolones are inhibitors
      of the Qp rather than the Qn site.

PMID- 9030271
TI  - A tribute to Fernando de Castro on the centennial of his birth.

PMID- 9030272
TI  - Prolegomena. Chemoreception upstream of transmitters.

PMID- 9030273
TI  - Daniel J. C. Cunningham. Oration at his funeral service.

PMID- 9030274
TI  - Re-examination of the carotid body ultrastructure with special attention to
      intercellular membrane appositions.
AB  - Ultrathin sections of the carotid body of adult rats, processed through freeze
      substitution after aldehyde-prefixation, showed a substantial number of presumed
      gap junctions between two adjacent chief cells, between chief and sustentacular
      cells, and between chief cells and carotid nerve terminals. The junctions showed
      a very narrow intercellular space of 2 nm and ranged in length from 200 nm to 1
      micron. They may form the morphological substrate for electrical coupling between
      cells, the occurrence of which has been demonstrated by electrophysiology.
      Further studies using freeze-fracture and immunocytochemistry for connexins are
      necessary to confirm this possibility. In addition, small tight junctions are
      present between chief and sustentacular cells, and between adjacent sustentacular
      cells.

PMID- 9030275
TI  - Two morphological types of chemoreceptor afferents innervate the rabbit carotid
      body.

PMID- 9030276
TI  - Mitochondrial division, blood vessel dilation, and large intercellular space
      expansion of goat carotid body during hypoxia.

PMID- 9030277
TI  - PO2 affinities, heme proteins, and reactive oxygen intermediates involved in
      intracellular signal cascades for sensing oxygen.
AB  - The oxygen partial pressure field in different organs ranging from 0 to 100 Torr
      is likely to be a mirror of oxygen sensitive intracellular signal cascades
      determining ion channel open probability, metabolic pathway activities and gene
      expression. High or low PO2 affinities of the particular signal cascade optimize
      the oxygen sensitive cellular response for adapting organ functions to variations
      of the oxygen supply conditions. The signal cascades are triggered by an oxygen
      sensor which is believed to be a heme protein. In some cases reactive oxygen
      intermediates (ROI) are acting as second messengers revealing these signal
      cascades as an evolutionary highly conserved principle first described in
      bacteria.

PMID- 9030278
TI  - Photochemical action spectra, not absorption spectra, allow identification of the
      oxygen sensor in the carotid body.

PMID- 9030280
TI  - Carotid chemosensory response to caffeine in developing cats.

PMID- 9030279
TI  - Mechanisms of carotid chemoreceptor resetting after birth. In vitro studies.
AB  - The results of these studies are consistent with the hypothesis that carotid
      chemoreceptor type-I cell resetting occurs, at least in part, at the level of the
      type-I cell. Furthermore, we have developed an in vitro model of newborn type-I
      cell resetting, in which freshly isolated glomus cells from newborns exhibit
      small, immature [Ca2+]i response to anoxia, but-after 72 hours in culture-[Ca2+]i
      responses convert to adult magnitude and profile. Finally, work so far suggests
      that glomus cell resetting in this model is modulated by oxygen tension. The
      mechanisms of glomus cell resetting remain unknown. Resetting of O2 sensitivity
      could result from withdrawal of tonic inhibitory influences present in vivo,
      changes in the oxygen sensor itself, changes in ion channel expression,
      modulation, and function, or other mechanisms occurring around the time of birth.
      Additional work is needed to determine the mechanisms of glomus cell resetting at
      the cellular level, and the role of O2 tension and other potential modulators of
      resetting.

PMID- 9030281
TI  - Role of potassium channels in hypoxic chemoreception in rat carotid body type-I
      cells.

PMID- 9030282
TI  - Is cytochrome P-450 involved in hypoxic inhibition of K+ currents in rat type I
      carotid body cells?

PMID- 9030283
TI  - Cyclic nucleotide analogs do not interfere with hypoxic inhibition of K+ currents
      in isolated rat type I carotid body cells.

PMID- 9030284
TI  - Modulation of voltage-gated Ca2+ channels by O2 tension. Significance for
      arterial oxygen chemoreception.

PMID- 9030285
TI  - Ca2+ channel currents in type I carotid body cells from normoxic and chronically
      hypoxic rats.

PMID- 9030286
TI  - Metabolic inhibitors affect the conductance of low voltage-activated calcium
      channels in brain capillary endothelial cells.

PMID- 9030288
TI  - Evaluation of gene expression in the rat carotid body using the differential
      display technique.

PMID- 9030287
TI  - Transmembrane currents in capillary endothelial cells are modulated by external
      Mg2+ ions.

PMID- 9030289
TI  - Induction of immediate early response genes by hypoxia. Possible molecular bases
      for systems adaptation to low pO2.

PMID- 9030290
TI  - Regulation of ionic conductances and gene expression by hypoxia in an oxygen
      sensitive cell line.
AB  - We have shown that the PC12 cell line is an excellent model system for
      investigations of the molecular and cellular processes involved in O2
      chemosensitivity. We have identified an O2-sensitive K channel in this cell line
      that mediates membrane depolarization, an increase in intracellular free Ca2+,
      and dopamine release during hypoxia. We also presented evidence which shows that
      expression of the gene for tyrosine hydroxylase, the rate-limiting enzyme in
      dopamine biosynthesis, is stimulated by reduced O2 tension in PC12 and type I
      carotid body cells. In addition, we have successfully identified the DNA
      sequences and trans-acting protein factors that regulate transcription of the TH
      gene during hypoxia. The mechanisms by which a reduction in O2 tension is
      transduced into alter cell function including increased gene expression remain
      unknown. Unpublished results from our laboratory show that the increased TH gene
      expression during hypoxia does not require activation of the cAMP-PKA signal
      transduction pathway. We propose that the increase in intracellular free Ca2+
      that occurs as a result of membrane depolarization might play an important role.
      Preliminary findings from our laboratory show that blockade of the voltage
      operated Ca2+ channel or chelation of intracellular Ca2+ prevent full activation
      of the TH gene during hypoxia.

PMID- 9030292
TI  - Effects of hypoxia on the intercellular channel activity of cultured glomus
      cells.
AB  - Dual voltage clamp experiments have shown that hypoxia induced by Na-dithionite
      or N2 reduced junctional macroconductance (Gj) in about 70% of cultured and
      coupled glomus cell pairs while increasing it in the rest. To explore possible
      mechanisms for these effects, we studied the activity of gap junction channels
      under similar conditions. The calculated single channel conductances (gj) fell
      into two categories. A low-conductance group, which was most frequently observed,
      had a mean gj of 27.8 +/- 0.29 pS (mean +/- SEM; n = 968 events). The other group
      had higher conductances (47.6 +/- 0.35 pS; n = 528). When PO2 was reduced
      (hypoxia), the low conductances did not change significantly in any of the
      junctions. The high-conductance units appeared less frequently in some junctions
      whereas in others they remained unaltered. Thus, rapid channel flickering during
      hypoxia may not be the only mechanism determining Gj during coupling or
      uncoupling. It is possible that slow (seconds) opening and closing of the
      channels could play an important role in this phenomenon.

PMID- 9030293
TI  - Reflections on the carotid nerve sensory discharge and coupling between glomus
      cells.

PMID- 9030291
TI  - Regulation of tyrosine hydroxylase mRNA stability by oxygen in PC12 cells.

PMID- 9030294
TI  - Generation of interspike intervals of rat carotid body chemoreceptors.

PMID- 9030296
TI  - Depolarization is a critical event in hypoxia-induced glomus cell secretion.

PMID- 9030295
TI  - The coupling between intracellular pH, ion transport, and chemosensory discharge.

PMID- 9030297
TI  - Co-cultures of rat petrosal neurons and carotid body type 1 cells. A model for
      studying chemosensory mechanisms.

PMID- 9030298
TI  - Responses of cat petrosal ganglion neurons are modified by the presence of
      carotid body cells in tissue cultures.

PMID- 9030299
TI  - Modifications of carotid body CO2 chemosensitivity in vitro.

PMID- 9030300
TI  - Intracellular acidosis potentiates carotid chemoreceptor responses to hypoxia in
      the absence of CO2-HCO3-.

PMID- 9030301
TI  - Central pH chemosensitivity in the newborn opossum Monodelphis domestica.

PMID- 9030302
TI  - Simultaneous measurements of cytosolic calcium ion and pH in cultured superior
      cervical ganglion cells of rat.

PMID- 9030303
TI  - Release of acetylcholine from the in vitro cat carotid body.

PMID- 9030304
TI  - Release of acetylcholine from cultured cat and pig glomus cells.

PMID- 9030305
TI  - Acetylcholine elevates intracellular Ca2+ via muscarinic and nicotinic receptors
      in rat carotid body type I cells.

PMID- 9030307
TI  - Localization of nicotinic acetylcholine receptors in cat carotid body and
      petrosal ganglion.

PMID- 9030306
TI  - The presynaptic component of a cholinergic mechanism in the carotid body
      chemotransduction of hypoxia in the cat.

PMID- 9030308
TI  - Effect of acetylcholine on intracellular calcium of carotid body cells of adult
      cats.

PMID- 9030309
TI  - Dopamine efflux from the carotid body during hypoxic stimulation.

PMID- 9030310
TI  - Catecholamine secretion from glomus cells is dependent on extracellular
      bicarbonate.

PMID- 9030311
TI  - Chronic hypoxia enhances expression of catecholamine biosynthesizing enzymes in
      rat carotid body.

PMID- 9030313
TI  - Dopamine D2 receptor mRNA isoforms expression in the carotid body and petrosal
      ganglion of developing rabbits.

PMID- 9030312
TI  - Intracellular Ca2+ deposits and catecholamine secretion by chemoreceptor cells of
      the rabbit carotid body.

PMID- 9030314
TI  - Domperidone as a tool to assess the role of dopamine within carotid body
      chemoreception.

PMID- 9030315
TI  - Adenosine increases the cAMP content of the rat carotid body in vitro.

PMID- 9030316
TI  - Endothelin modulates chemoreceptor cell function in mammalian carotid body.

PMID- 9030317
TI  - Expression and localization of enkephalin, substance P, and substance P receptor
      genes in the rat carotid body.

PMID- 9030318
TI  - Neuropeptide processing enzymes of the carotid body. Biochemical and
      immunological characterization of carboxypeptidase activity.

PMID- 9030319
TI  - Coexistence of neuropeptides in the amphibian carotid labyrinth. An application
      of double immunolabelling in combination with a multiple dye filter.

PMID- 9030320
TI  - Secretoneurin. A novel carotid body peptide.

PMID- 9030321
TI  - Carbon monoxide excretion, not oxygen secretion?

PMID- 9030322
TI  - Carbon monoxide and carotid body chemoreception.

PMID- 9030323
TI  - Regulation of neuronal nitric oxide synthase gene expression by hypoxia. Role of
      nitric oxide in respiratory adaptation to low pO2.

PMID- 9030324
TI  - Coherence of chemosensory discharges in cats' carotid nerves. Cooperative inputs
      or redundant afferences?

PMID- 9030326
TI  - Afferent input from peripheral chemoreceptors in response to hypoxia and amino
      acid neurotransmitter generation in the medulla.

PMID- 9030325
TI  - Carotid chemoreflex. Neural pathways and transmitters.
AB  - The chemoreceptor projection site encompasses a midline area (0-0.5 mm caudal, 0
      0.5 mm lateral and 0.3-0.5 deep with respect to the calamus scriptorius) which
      includes the commissural subnucleus of NTS. The chemosensitive neurons located in
      this site fire tonically, without any rhythmic relation to the phrenic nerve
      bursts, and are not responsive to baroreceptor stimulation. These neurons may
      serve as a pre-central pattern generator for respiration. The mechanisms which
      mediate respiratory responses (i.e., PN responses) to carotid chemoreceptor
      stimulation are as follows. Activation of carotid chemoreceptors results in the
      release of an excitatory amino acid (probably glutamate) in the chemoreceptor
      projection site; both NMDA and non-NMDA receptors in this site mediate the
      responses to chemoreceptor stimulation. The chemosensitive neurons send
      projections (which have not been identified yet) to respiratory neurons. Unlike
      in the neonatal rat, the inspiratory drive to the phrenic motoneurons is mediated
      by both NMDA and non-NMDA receptors. The PN response to chemoreceptor stimulation
      are also mediated by NMDA and non-NMDA receptors located in the phrenic motor
      nucleus. Cardiovascular responses to chemoreceptor stimulation are mediated by
      neural pathways connecting the chemosensitive neurons to the rostral
      ventrolateral medullary pressor area. These projections are glutamatergic.
      Activation of the sympatho-excitatory neurons in the rostral ventrolateral
      medulla results in pressor and tachycardic responses characteristic of
      chemoreceptor activation.

PMID- 9030327
TI  - Augmented ventilatory response to sustained normocapnic hypoxia following 100% O2
      breathing in humans.

PMID- 9030328
TI  - Role of carotid bodies in the guinea-pig.

PMID- 9030329
TI  - Effects of continuous intracarotid infusion of dopamine during long-term hypoxia
      in awake goats.

PMID- 9030331
TI  - Dynamic sensitivity of carotid chemoreceptors to CO2 in the newborn lamb.

PMID- 9030330
TI  - The role of carotid body CO2 during ventilatory acclimatization to hypoxia in the
      goat.

PMID- 9030332
TI  - A phospholipase C inhibitor impedes the hypoxic ventilatory response in the cat.

PMID- 9030333
TI  - Modelling the peripheral chemosensory drive of ventilation on basis of homogenous
      sensory units.

PMID- 9030334
TI  - Functional activation of cerebral glucose uptake after carotid body stimulation.

PMID- 9030335
TI  - Prolonged hemodynamic effects of intermittent, brief chemoreceptor stimulation in
      humans.

PMID- 9030336
TI  - Interaction between the bradycardic responses to upper airway negative pressure
      and carotid chemoreceptor stimulation in the anaesthetised rabbit.

PMID- 9030337
TI  - Chemoreceptors in autonomic responses to hypoxia in conscious rats.

PMID- 9030338
TI  - The effect of sympathetic nerve stimulation on ventilation and upper airway
      resistance in the anaesthetized rat.

PMID- 9030339
TI  - Ventilatory and upper airway muscle responses to upper airway CO2 in
      anaesthetized neonatal guinea-pigs.

PMID- 9030341
TI  - Effects of hypercapnia on steady state, phenylephrine-induced tension in isolated
      rings of rat pulmonary artery.

PMID- 9030340
TI  - Neurogenic inflammation. A model for studying efferent actions of sensory nerves.
AB  - Several lines of evidence suggest that sensory nerves of the carotid body have an
      efferent function in addition to their afferent function of conducting
      chemoreceptive impulses to the brain. However, it has been difficult to document
      the release of substances from sensory nerve terminals on glomus cells and to
      determine whether such an efferent function plays a role in chemoreception. By
      comparison, the phenomenon of neurogenic inflammation has been relatively easy to
      study in rats and guinea pigs and has proven to be an informative model system
      for analyzing efferent actions of sensory nerves. The main characteristic of
      neurogenic inflammation is plasma leakage. Chemical irritants that activate
      unmyelinated sensory nerves cause plasma leakage in the skin, respiratory tract,
      and other organs by triggering the release of substances from sensory nerve
      fibers. Substance P, which is synthesized and released by some sensory neurons,
      appears to be the main active mediator, although other tachykinins, calcitonin
      gene-related peptide, and perhaps other peptides may also participate. Neurogenic
      inflammation results from the action of substance P on NK1 receptors, as
      demonstrated by selective NK1 receptor agonists and antagonists. The NK1
      receptors involved in plasma leakage are located on the endothelial cells of
      postcapillary venules and collecting venules. Within seconds of the activation of
      NK1 receptors by substance P, gaps form in the endothelium of target vessels. The
      endothelial gaps are transient, and the leak normally ends in a few minutes.
      However, the magnitude of the response can increase in pathological conditions
      such as Mycoplasma pulmonis infection in rats, which results in a chronic
      inflammatory disease of the respiratory tract. The infected airway mucosa becomes
      abnormally vascular as a result of angiogenesis, and the endothelial cells of the
      newly formed vessels express increased numbers of NK1 receptors and thus are
      abnormally sensitive to substance P. Studies of neurogenic inflammation not only
      have helped to understand the efferent actions of sensory nerves but also have
      given insight into the mechanism and consequences of inflammatory changes in
      endothelial cells and in the plasma leakage that follows.

PMID- 9030342
TI  - Early neuropsychological sequelae of aneurysm surgery and subarachnoid
      haemorrhage.
AB  - In order to disclose the immediate cognitive sequelae of early aneurysm surgery
      and subarachnoid haemorrhage (SAH), a series of 28 patients was examined
      neuropsychologically one to 13 days (median 5 days) after surgery. Cognitive
      deficits emerged in short- and long-term memory, language and in different
      functions of attention. There was no effect of ACoA aneurysm location on
      neuropsychological test performance. No substantial effect of premature aneurysm
      rupture or surgical approach could be revealed. Temporary clipping of vessels was
      associated with significantly worse selective attention and phasic alertness (p <
      0.05, respectively). Partial resection of the gyrus rectus led to a worse short
      term memory (p = 0.02). In regression analyses, the duration of temporary
      clipping was associated with worse short-term memory (adjusted r2 = 0.68; p =
      0.007) and decreased phasic alertness (adjusted r2 = 0.47; p = 0.035). The
      clinical state on admission (Hunt and Hess) predicted an impaired phasic
      alertness (adjusted r2 = 0.43; p = 0.004). It is concluded from the results, that
      certain procedures and events in aneurysm surgery can have neuropsychological
      effects. The present study is restricted by the small sample size. Therefore, a
      prospective study with a larger patient sample is required for further
      confirmation of the present findings.

PMID- 9030343
TI  - The variations of Sylvian veins and cisterns in anterior circulation aneurysms.
      An operative study.
AB  - The anatomical variations of Sylvian vein and cistern were investigated during
      the pterional approach in 230 patients with 276 aneurysms of anterior circulation
      arteries, that were operated on at the Neurosurgical Department of Ataturk
      University Medical School. Erzurum, Turkiye. All patients underwent radical
      surgery for aneurysm by the right or left pterional approach. The findings were
      recorded during surgical intervention and observed through the slides and
      videotapes of the operations. In our study, we surgically classified the
      variations of the Sylvian vein, according to its branching and draining patterns.
      Type I: The fronto-orbital (frontosylvian), fronto-parietal (parietosylvian) and
      anterior temporal (temporosylvian) veins drain into one sylvian vein. Type II:
      Two superficial Sylvian veins with separated basal vein draining into the
      sphenoparietal and Rosenthal's basal vein. Type III: Two superficial Sylvian
      veins draining into the sphenoparietal and the superior petrosal veins. Type IV:
      Hypoplastic superficial Sylvian vein and the deep one. Four types of Sylvian vein
      variations were defined as follows. The Type I was seen in 45% (n = 103), the
      Type II was found in 29% (n = 67), Type III was recorded in 15% (n = 34) and Type
      IV, or hypoplastic and deep form was discovered in 11% (n = 26) of patients. The
      course of the Sylvian vein was on the temporal side (Temporal Coursing) in 70
      percent of the cases (n = 160), on the frontal side (Frontal Coursing) in 19% of
      the patients (n = 45) and in 8 percent of the cases (n = 18) in the deep
      localization (Deep Coursing). Only 3 percent of the cases (n = 7) showed a mixed
      course. The variations of the Sylvian cisterns were classified into three types,
      according to the relationships between the lateral fronto-orbital gyrus and the
      superior temporal gyrus. In Sylvian Type, the frontal and temporal lobes are
      loosely (Sylvian Type A, Large) or tightly (Sylvian Type B, Close and Narrow)
      approximated on the surface thereby covering the area of the Sylvian cistern. In
      frontal type, the proximal, part of the lateral fronto-orbital gyrus herniated
      into the temporal lobe. In temporal type, the proximal part of the superior
      temporal gyrus hemiated into the lateral fronto-orbital gyrus. The variations of
      the Sylvian cisterns in 230 patients were as follows: in 31% (n = 71) Sylvian
      Type A, in 21% (n = 48) Sylvian Type B, in 34% (n = 78) Frontal Type, and in 14%
      (n = 33) Temporal Type. We concluded that venous perfusion disorder of the brain
      is the most important factor during the pterional approach. Careful
      intraoperative assessment and protection of the Sylvian vein, which is a surgical
      pitfall, is an indispensable part of the operation. The recognition of the
      anatomical variations of the Sylvian vein and cistern, and the detailed knowledge
      of the microvascular relationships at that level will allow the neurosurgeon to
      construct a better and safter microdissection plan, to save time and can prevent
      postoperative neurological deficits.

PMID- 9030344
TI  - Management of symptomatic carotid stenoses with coincidental intracranial
      aneurysms.
AB  - There are at present strong indications for surgery in patients suffering from
      symptomatic extracranial carotid stenoses of > 70%. Surgery of coincidental
      aneurysms is a still debated problem, but there is general agreement that it is
      indicated in selected cases according to the patient's life-expectancy and size
      and site of the aneurysm. The coexistence of these two lesions raises a decision
      making problem. We reviewed 389 endarterectomies and found 12 intracranial berry
      aneurysms in 10 (2.6%) patients. All the 10 patients were harbouring a
      symptomatic carotid stenosis of > 70%. Since the correction of a stenosis
      increases blood flow to an aneurysm, our approach was to first operate on the
      intracranial lesion and then the stenosis in 7 patients harbouring aneurysms > 5
      mm. Two patients affected by small aneurysms < 5 mm of an A2 azygos and left
      internal carotid artery underwent left endarterectomy only. The last patient was
      submitted first to percutaneous angioplasty of a left stenosis, then to open
      surgery of a contralateral middle cerebral aneurysm and finally to intravascular
      occlusion of a small aneurysm of the left internal carotid bifurcation by menas
      of a coil; this policy was adopted in order to restore normal haemodynamic
      conditions before the intracranial procedure. There was no mortality or permanent
      morbidity following surgery for aneurysm or endarterectomy. Transient morbidity
      occurred in 2 cases after clipping of aneurysms of the anterior communicating and
      middle cerebral arteries. Our results suggest that surgery of coincidental
      aneurysms may give good results even when there is a severe symptomatic stenosis
      in the neck. Moreover, the presence of a small intracranial aneurysm does not
      seem to be an additional risk factor for endarterectomy. When the lesions are on
      different sides, it may be better to treat the stenosis first if it decreases the
      ipsilateral cerebral blood flow.

PMID- 9030347
TI  - Analysis of abnormal jugular bulb oxygen saturation data in patients with severe
      head injury.
AB  - Jugular bulb oximetry provides the first bedside, continuously available
      information on cerebral perfusion adequacy. An extensive analysis was made of all
      jugular bulb oxygen saturation (SjO2) data obtained in 50 patients suffering from
      severe head injury. A total of 176 periods (more than 30 minutes) with reliable,
      abnormal SjO2-values was observed, with 62 desaturation periods (SjO2 < 55%) and
      114 high SjO2-periods (SjO2 > 80%). Jugular desaturation periods were
      predominantly observed in the first 2 days of monitoring and seemed the most
      closely correlated to lowered cerebral perfusion pressure and lowered arterial
      carbon dioxide tension. The high SjO2-values were more equally distributed over
      the first 5 days of monitoring and seemed mostly correlated to increased arterial
      carbon dioxide tension. Highlights of the general management of severely head
      injured patients is discussed, focussing attention on the importance of cerebral
      perfusion pressure and normoventilation.

PMID- 9030346
TI  - Outcome of 31 intracranial haemangiopericytomas: poor predictive value of cell
      proliferation indices.
AB  - Cell proliferation indices of 31 primary intracranial haemangiopericytomas (HPC)
      and their recurrences and metastases were correlated with the long-term
      recurrence, metastasis and survival rates. Paraffin-embedded specimens were used
      for K-67, PCNA and p53 immunostainings and for estimation of S-phase fraction (S
      PF) in flow cytometry. The median Ki-67 and PCNA indices and S-PFs were 10.4,
      3.2, and 4.0 for primary HPCs and 14.1, 14.1, and 5.5 for recurrences,
      respectively. High indices were associated with higher recurrence, metastasis and
      death rates, but not at the p < or = 0.5 level. Consequently, these indices do
      not seem useful in planning of treatment and follow-up of meningeal HPCs.
      Meningeal HPCs, in contrast to meningiomas, recur almost always despite seemingly
      complete removal and often metastasize elsewhere in the body. This difference
      between two sharply demarcated tumours must reflect particularly adhesive and
      infiltrative properties of HPC cells and not just higher proliferation potential.

PMID- 9030348
TI  - Endoscopy assisted transsphenoidal surgery for pituitary adenoma. Technical note.
AB  - Inspired by an experience with endoscopic paranasal sinus surgery, an endoscope
      was applied in transsphenoidal pituitary surgery. This endoscopic transsphenoidal
      technique has been used in 45 cases of pituitary adenomas. Using a 4 mm rigid
      endoscope, the pituitary adenoma is removed through a nostril. A zero-degree
      endoscope is used for micro-adenomas. A combination of a 0-degree endoscope and a
      30-degree endoscope is used for macro-adenomas that have extended to the
      suprasellar region. Although it is early in our experience with a small number of
      patients, the short-term surgical results have been encouraging with patients'
      short hospital stay and minimum morbidity. The endoscopic technique that has
      evolved with our experience is described with two cases of pituitary adenomas.

PMID- 9030345
TI  - Correlation of intra-operative ultrasound with histopathologic findings after
      tumour resection in supratentorial gliomas. A method to improve gross total
      tumour resection.
AB  - The aim of this study was to evaluate whether intra-operative ultrasound (= IOUS)
      is a suitable tool to detect residual tumour tissue after gross total resection
      in supratentorial gliomas. During a period of 18 months 45 patients with
      supratentorial gliomas (38 high-grade and 9 low-grade, according to the WHO
      grading system [42]) were operated on. A series of 78 biopsies was taken from the
      resection cavity under continuous sonographic control at the end of surgery.
      Gross total tumour resection was intended in 34 patients (= 76%). The biopsy
      specimens were matched with the sonographic features at each biopsy site. The
      sonographic appearance of the resection margins were classified into 2 groups:
      (1) Irregular hyperechoic areas extending from the cavity into the iso-echogenic
      brain tissue and (2) a dense small (< or = 3 mm in diameter) rather regular
      hyperechoic rim surrounding the resection cavity. 47 out of 53 biopsies taken
      from hyperechoic areas (group I) (36 high-grade/11 low-grade) revealed solid
      tumour tissue (= 89%). 34 (= 72%) of these 47 areas were microscopically assessed
      as inconspicuous by the surgeon. 6 samples (4 high-grade/2 low-grade) contained
      tumour infiltration zone. 25 biopsies (23 high-grade/2 low-grade) taken from the
      hyperechoic rim [group 2] were diagnosed as follows: Normal brain tissue in 11,
      tumour infiltration zone in 8 and solid tumour tissue in 6 cases. Of 34 cases
      with "gross total removal" according to the surgeon's assessment 25 showed
      sonographic signs of residual tumour tissue, which was confirmed histologically
      as solid tumour tissue in 22 of these cases. It is concluded, that IOUS following
      resection of supratentorial gliomas can detect residual tumour tissue with high
      specificity and thus improve gross total resection. However, a thin hyperechoic
      rim surrounding the resection cavity (less than 3 mm in diameter) is a non
      specific finding, which can mask thin residual tumour layers and therefore needs
      further evaluation of its nature.

PMID- 9030349
TI  - Life threatening intracranial complications of frontal sinus osteomas: report of
      two cases.
AB  - Paranasal sinuses osteomas are known as biological benign tumours. However, due
      to the peculiar anatomical relationships, patients harbouring an osteoma within
      the frontal sinus are exposed to serious orbital and intracranial complications.
      We report two unusual cases of intracranial mucocoeles associated with frontal
      osteomas. In one of them, a superposed tension aerocoele required emergency
      surgery. Although aggressive treatment of asymptomatic osteomas is not warranted,
      these lesions must be carefully observed and resected as soon as they show
      clinical and/or radiological signs of progression. The physiopathological and
      clinical aspects are discussed.

PMID- 9030350
TI  - A flexible metal ventricular catheter for treatment of complicated and protracted
      infections of the cerebrospinal fluid spaces: preliminary experiences.
AB  - In the management of shunt infection, the use of ventricular catheters made of
      silicone rubber for the temporary external drainage of cerebrospinal fluid (CSF)
      is general practice. However, the eradication of the primary source of infection
      may be hindered by the affinity of bacteria to silicone-based material. Compared
      to silicone catheters, a metal drainage device for temporary ventriculostomy
      appears to offer more favourable conditions for successful eradication of the
      infection. Since metal needles cannot be implanted permanently and since their
      screw-type fixation precludes attachment to the skulls of infants or small
      children, we developed a flexible metal catheter. This catheter was used
      exclusively for the treatment of particularly serious or chronic infections of
      the CSF spaces. The catheter is made of implantation steel and consists of a
      corrugated tube that renders it flexible. Cerebrospinal fluid drains into a
      receptable bulb at the tip of the tube. Tubing of other materials may be
      connected to the end of the metal catheter for either external or internal
      drainage. It was implanted as a temporary and later permanent CSF drainage in 7
      male patients aged from 4 to 60 years, who suffered from chronic, recurrent
      ventriculitis (n = 5) with an average of 7 previous surgical revisions, as well
      as from complex infections (n = 2; basal tuberculous meningitis, brain abscess).
      The infections were successfully eliminated in 6 patients. In the remaining
      patient, the metal catheter for external ventriculostomy had to be removed after
      4 days due a leakage of CSF; it was replaced by a silicone catheter and later on
      by a needle drainage. Other complications, such as secondary infection or
      intracerebral haemorrhage, did not occur. The average duration of external CSF
      drainage via the flexible metal catheter was 27 days (range 4-50 days). In 4
      patients, the CSF drainage was converted to a permanent ventriculoperitoneal
      shunt using a new flexible metal catheter. At the time of post-operative follow
      up examination (average = 34 weeks), all shunts were functioning and there was no
      evidence of infection. In cases of especially complicated and protracted CSF
      infections, the flexible metal ventricular catheter is a promising device for
      treatment.

PMID- 9030351
TI  - Cellular targets of exogenous tumour necrosis factor-alpha (TNF alpha) in human
      gliomas.
AB  - To identify the cellular targets of TNF alpha in human gliomas, a total of 30
      surgical specimens (12 glioblastomas, 4 anaplastic astrocytomas, 3 astrocytomas,
      7 brains adjacent to tumour (BAT), 4 histologically normal-appearing brains) were
      examined by in vitro binding technique using biotinylated TNF alpha. The TNF
      binding sites (TNF-BS) were recognized in the tumour cells in 8 of the 12
      glioblastomas, 3 of the 4 anaplastic astrocytomas and in all the 3 astrocytomas.
      The TNF-BS were also recognized in the vascular endothelial cells in all these
      cases. The presence of TNF-BS in blood vessels ranged from 7.7 to 74.4% of the
      background vessels. This wide range of variation in the presence of TNF-BS within
      the tumour cells and tumour blood vessels may be relevant to the variable
      response of individual tumours to TNF alpha therapy. Since the tissue of normal
      brain, which lacks TNF-BS, might hardly be affected by this cytokine,
      administration of TNF alpha may be considered as an adjuvant therapy in selected
      groups of patients.

PMID- 9030352
TI  - Matrix metalloproteinase-9 secretion by human pituitary adenomas detected by cell
      immunoblot analysis.
AB  - Twenty-two pituitary adenomas were examined on the secretion of matrix
      metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      using a cell immunoblot assay, and discussed regarding an association between
      cavernous sinus invasion and the secretion of these proteins. The cell immunoblot
      assay, a kind of immunoblot procedure, is able to detect proteins at the single
      cell level and to detect the incidence of tumour cells secreting the target
      proteins in the total tumour cell population. The incidence of tumour cells
      secreting MMP-9 was significantly higher in invasive adenomas than in noninvasive
      ones. On the other hand, TIMP-1 secretion was not detected in any adenomas in
      this study. This result suggested that MMP-9 secretion, and especially the number
      of MMP-9-secreting cells, may be associated with cavernous sinus invasion of
      pituitary adenomas.

PMID- 9030353
TI  - The correlation of Ki-67 staining indices with tumour doubling times in regrowing
      non-functioning pituitary adenomas.
AB  - In order to improve our ability to predict the regrowth of nonfunctioning
      pituitary adenomas, we tried to assess the correlation between growth fractions
      with Ki-67 and PCNA (proliferating cell nuclear antigen) and tumour doubling
      times in regrowing tumours, and also to find out any difference of growth
      fractions between the regrowing and the cured cases. In 33 patients with non
      functioning pituitary adenomas, 14 cases including 11 with cavernous sinus
      invasion showed residual tumour on MRI after the operation (regrowing group) and
      19 cases had no tumour regrowth on MRI within 5 years after the operation (cured
      group). Immunocytochemical studies were done with monoclonal antibodies (anti
      PCNA, anti-Ki-67: MIB-1). The growth fraction of each tumour was estimated by
      calculating the ratio of the positive nuclei to the total number of tumour cells
      with the aid of an image analyser (Mac SCOPE). The tumour doubling times were
      estimated from serial CT or MRI with the aid of the image analyser (NIH image).
      Ki-67 staining indices ranged from 0.2% to 1.5% (n = 14, 0.86 +/- 0.10%; mean +/-
      SEM) in the regrowing group, and from 0.1% to 0.5% (n = 19, 0.23 +/- 0.03%) in
      the cured group. PCNA staining indices of the regrowing group ranged from 0.6% to
      24% (n = 14, 3.7 +/- 1.6%). In the regrowing group, the tumour doubling times
      ranged from 200 to 2550 days (930 +/- 180 days), and showed a significant inverse
      correlation with Ki-67 staining indices, but no correlation with PCNA staining
      indices. The regrowing group showed a significantly higher Ki-67 staining index
      (n = 14, 0.86 +/- 0.10%) than the cured group (n = 19, 0.23 +/- 0.03%) (p <
      0.01). These results indicate that immunocytochemical studies using MIB-1 may be
      better than those with PCNA for the prediction of regrowth in non-functioning
      pituitary adenomas. Immunocytochemical study with MIB-1 could lead to the
      accurate prediction of the rapid regrowing lesions in non-functioning adenomas.

PMID- 9030355
TI  - Aneurysm of superior branch of anterior choroidal artery mimicking carotid
      bifurcation aneurysm--case report.
AB  - Aneurysm of the superior branch of anterior choroidal artery is very rare. We
      report this rare case with unique angiographic findings mimicking an internal
      carotid bifurcation aneurysm. A 35-year-old woman was admitted to our hospital
      because of severe headache. Lumbar puncture disclosed numerous red blood cells.
      Computed tomography revealed an enhanced circular area in the left basal cistern
      with moderate hydrocephalus. Cerebral angiography showed a saccular aneurysm near
      the left internal carotid bifurcation. During operation, the aneurysm was not
      found at the internal carotid bifurcation, but located deeper budding from the
      superior branch of the anterior choroidal artery. The aneurysm was successfully
      clipped. The postoperative course was favourable without any neurological
      deficit. The postoperative angiogram showed that the aneurysm was clipped well
      with preservation of the main trunk of the anterior choroidal artery. Computed
      tomography of the brain did not show any infarction area, 3 months after the
      surgery. The uniqueness of this case is the favourable outcome after sacrificing
      the superior branch of the anterior choroidal artery. The role of collaterals of
      the anterior perforating substance is emphasized.

PMID- 9030354
TI  - Recurrence of meningiomas versus proliferating cell nuclear antigen (PCNA)
      positivity and AgNOR counting.
AB  - Meningiomas have a wide range of biological potential and clinical behaviour.
      Histological findings are helpful in recognizing the malignant potential but
      often fail to correlate with clinical behaviour. This study attempts to correlate
      the silver nucleolar organizer regions (AgNORs) and proliferating cell nuclear
      antigen (PCNA) with clinicopathological features of biological activity. Thirty
      four completely resected meningiomas were classified as benign [19], atypical [6]
      and malignant [9]. Forty-eight initial and recurrent tumour materials were
      investigated for staining of AgNORs and immunohistochemistry using monoclonal
      antibodies against PCNA (clone 19A2 and PC10). There were no difference between
      the recurrent and non-recurrent cases with regards to AgNOR, PC10 and 19A2
      values. Also, no significant difference was found between the primary and
      recurrent tumours. Both PC10 and 19A2 labelling indices (LI) showed a significant
      difference between benign and malignant meningiomas. The 19A2 LI was 0.56 +/-
      0.21 in benign and 2.45 +/- 16 in atypical meningiomas. The 19 A2 counts showed
      significant difference between benign and atypical tumours but PC10 values failed
      to show such a correlation AgNOR and PCNA indices were not found to be useful in
      predicting recurrences compared to the surgical procedure and histopathological
      criteria.

PMID- 9030356
TI  - Intracranial foreign-body granuloma caused by oxidized cellulose.

PMID- 9030357
TI  - Radiation induced intracranial leiomyosarcoma: its histopathological features.
AB  - This is a case of intracranial sarcoma which was recognized 23 years after
      irradiation therapy for pituitary adenoma. Four operations were performed because
      of recurrences with a short interval between each operation.
      Immunohistochemically, the tumour cells were stained for smooth muscle actin,
      human muscle actin and vimentin. It was verified as a leiomyosarcoma. This report
      is the first case of intracranial leiomyosarcoma associated with radiation
      therapy in pituitary adenoma.

PMID- 9030358
TI  - Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but
      not healthy semen donors.
AB  - OBJECTIVE: To ascertain the prevalence of Kaposi's sarcoma-associated herpesvirus
      (KSHV), also known as human herpesvirus (HHV) type 8, and cytomegalovirus (CMV)
      DNA in semen was investigated. METHODS: Amplification by nested polymerase chain
      reaction was used to detect viral DNA sequences in samples from 24 HIV-infected
      gay men, 15 of them with Kaposi's sarcoma (KS), and 115 healthy donors. RESULTS:
      Six of the 24 HIV-infected patients had detectable HHV-8 DNA in their semen:
      three of the 15 patients with KS and three of the nine patients without KS. CMV
      DNA was detected in 20 semen samples from HIV-infected patients. None of the
      semen samples from healthy donors had detectable HHV-8 DNA and rates of CMV DNA
      detection were low (3%). CONCLUSIONS: The study demonstrates the presence of HHV
      8 in semen from HIV-infected individuals with, or at risk, of developing KS and
      the potential for sexual transmission of the virus. We found no evidence of HHV-8
      in the semen of HIV-uninfected donors.

PMID- 9030359
TI  - HIV-1 Tat protein can transactivate a heterologous TATAA element independent of
      viral promoter sequences and the trans-activation response element.
AB  - OBJECTIVE: To determine whether the HIV-1 transactivator protein Tat acts as a
      DNA sequence-specific transcription factor and activates transcription from a
      heterologous TATAA element in the absence of the trans-activation response (TAR)
      element and other sequences in the HIV-1 long terminal repeat (LTR). DESIGN:
      Activating protein-1 (AP-1) and Tat-induced transcription were assessed using Jun
      and hybrid Tat/Jun-expression plasmids and reporter gene constructs which
      contained AP-1 binding sites upstream of the rat prolactin TATAA element or an
      HIV-1 LTR construct in which AP-1 binding sites replaced the TAR element.
      METHODS: Tat-induced transcription was determined following transient
      transfection of colon epithelial cell lines with reporter gene constructs and
      Tat/Jun-expression plasmids in which Tat was fused to the DNA binding domain of
      Jun. Activation of prolactin (PL) and LTR reporter genes was assessed by
      luciferase (LUC) or chloramphenicol acetyltransferase (CAT) activity in cellular
      extracts. RESULTS: Cotransfection of cells with Tat/Jun and the AP-1 PL LUC or
      LTR AP-1 CAT reporter plasmid resulted in a marked increase in reporter gene
      activity which was comparable with that induced by transfection of cells with
      several different AP-1 expression plasmids (e.g., JunD, JunB, c-Fos), or that
      elicited by stimulation of the cells transfected with LTR AP-1 CAT plasmids with
      phorbol ester or tumor necrosis factor-alpha. Tat-induced transcription was DNA
      mediated since both a Jun DNA binding domain fused to Tat as well as AP-1 binding
      sites within the promoter were required for the induction of CAT expression.
      CONCLUSIONS: Tat-activated transcriptor can occur strictly through a heterologous
      TATAA element independent of TAR and Sp1 binding sites or other HIV-1 LTR
      sequences. Tat appears to increase transcription initiated through the TATAA
      element by mechanisms similar to that of DNA sequence-specific transcription
      factors.

PMID- 9030360
TI  - Perturbations of glucose metabolism associated with HIV infection in human
      intestinal epithelial cells: a multinuclear magnetic resonance spectroscopy
      study.
AB  - OBJECTIVE: To analyse the effect of HIV-1 infection on the glucose metabolism of
      human intestinal epithelial cells. METHODS: HT-29 cells were infected with HIV
      1NDK and studied 3 weeks (acutely infected cells) or 9 months (chronically
      infected cells) post-infection. Perchloric acid extracts were analysed by high
      resolution 1H, 31P and 13C nuclear magnetic resonance spectroscopy. Metabolite
      concentrations and specific 13C enrichments were quantified for chronically
      infected, acutely infected and control cells grown in Dulbecco's modified Eagle's
      medium containing natural-abundance or 1-13C-enriched glucose to determine
      significant differences between infected and non-infected cells. RESULTS:
      Chronically HIV-infected cells showed alterations in glycerol-3-phosphate (+40%),
      fructose-1,6-diphosphate (-66%), uridine diphosphate glucuronic acid (-33%),
      lactate (+75%) and [1-13C]glucose (+181%) levels, and in specific lactate 3-13C
      enrichment (+19%) when compared with controls. Acutely infected cells exhibited
      decreased fructose-1,6-diphosphate (-58%) and increased nicotinamide adenine
      dinucleotide (+33%) levels relative to controls. CONCLUSION: HIV-1 infection
      results in a disturbance of glycolytic and oxidative activities in human
      intestinal epithelial cells. This finding supports the concept that HIV-1 may
      directly impair some metabolic functions of the intestinal epithelium, and that
      it can be considered a potential aetiological agent for HIV-associated
      enteropathy.

PMID- 9030361
TI  - Prevention of simian immunodeficiency virus, SIVsm, or HIV-2 infection in
      cynomolgus monkeys by pre- and postexposure administration of BEA-005.
AB  - OBJECTIVE: To study the possibilities and limitations of postexposure treatment
      to prevent the establishment of infection after accidental exposure to HIV.
      DESIGN AND METHODS: The effect of 2,3'-dideoxy-3'-hydroxymethyl cytidine (B1 A
      005) was investigated on acute simian immunodeficiency virus (SIV) and HIV-2
      infections in macaques in pre- and postexposure treatment experiments. RESULTS:
      Postexposure treatment with BLA-005 (3 x 10 mg/kg) for as short as 3 days
      prevented infection with SIVsm after intravenous or rectal inoculation. Infection
      with HIV-2 could also be blocked by postexposure BFA-005 treatment. CONCLUSION:
      This study shows that therapeutic intervention can block early systemic and
      mucosal infections with SIV and HIV-2. Further evaluation is ongoing.

PMID- 9030362
TI  - Itraconazole cyclodextrin solution: the role of in vitro susceptibility testing
      in predicting successful treatment of HIV-related fluconazole-resistant and
      fluconazole-susceptible oral candidosis.
AB  - OBJECTIVES: This study assessed the ability of in vitro susceptibility testing of
      clinical Candida isolates to predict in vivo response to itraconazole
      cyclodextrin solution. METHODS: One hundred specimens were obtained from HIV
      positive patients with oral thrush, of which 72 speciments were from patients who
      were clinically unresponsive to fluconazole at standard doses and had fluconazole
      resistant isolates in vitro. Susceptibility to itraconazole was assessed by
      measuring the relative growth of an isolate in liquid medium containing a single
      concentration of itraconazole and then expressing growth in itraconazole as a
      percentage of growth in antifungal-free medium. RESULTS AND CONCLUSIONS: Where
      specimens yielded only one isolate, a cut-off relative growth in itraconazole of
      68% discriminated between isolates from patients failing to respond clinically to
      itraconazole solution and those from patients successfully treated with the
      preparation (specificity 100%; sensitivity 88%). The presence of mixed infection
      reduced the predictive accuracy of the test. Only 30% of fluconazole-resistant
      isolates were cross-resistant to itraconazole. No isolates were resistant to
      itraconazole but susceptible to fluconazole. Non-response to itraconazole
      solution was attributed to resistant yeast infection in the majority of cases,
      and this susceptibility method accurately identified specimens from patients
      unlikely to respond to the drug.

PMID- 9030363
TI  - Correspondence between the effect of zidovudine plus lamivudine on plasma HIV
      level/CD4 lymphocyte count and the incidence of clinical disease in infected
      individuals. North American Lamivudine HIV Working Group.
AB  - OBJECTIVES: To investigate whether apparently beneficial changes in plasma HIV
      RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are
      associated with a corresponding clinical benefit. METHODS: For 620 patients in
      two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV)
      plasma HIV RNA and CD4 lymphocyte count changes were compared in patients
      randomized to 3TC plus ZDV and patients randomized to other treatment arms. The
      effect of therapy on the HIV RNA level and CD4 count was compared with the effect
      of therapy on clinical endpoints over the same time period. RESULTS: Median
      baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 x
      10(6)/l for CD4 count. During the trial a significantly lower HIV RNA level and
      higher CD4 count was sustained in the ZDV/3TC group compared with the other
      group, with a difference in the median area under the curve from baseline per
      month of follow-up of 0.38 log10 copies/ml HIV RNA and 0.18 log2 x 10(6)/l CD4
      cells (P < 0.001 in each case). For patients who were initially asymptomatic or
      in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4
      count was 3.14 [95% confidence interval (CI), 1.44-6.83] and for a 10-fold higher
      HIV RNA level was 3.22 (1.20-8.59). The RH progression to AIDS expected with
      ZDV/3TC compared with the control treatments, given the observed effects of
      treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed
      value was 0.16 (0.03-0.74). After adjustment for HIV RNA and CD4 changes over
      time the observed RH of progression to AIDS for ZDV/3TC treatment compared with
      controls was increased to 0.36 and was no longer significant (95% CI, 0.07-1.85).
      CONCLUSION: In this analysis of two trials, the effects of ZDV/3TC in reducing
      plasma HIV RNA and raising peripheral blood CD4 counts were associated with
      concurrent clinical benefits and the effect of treatment on these markers could
      account for at least part of the clinical benefits of therapy that were observed.

PMID- 9030364
TI  - A prospective study of criteria for the diagnosis of toxoplasmic encephalitis in
      186 AIDS patients. The BIOTOXO Study Group.
AB  - OBJECTIVE: To define the factors associated with diagnosis of toxoplasmic
      encephalitis (TE) in AIDS patients; and to establish a rational procedure for the
      clinician faced with a decision concerning empiric antitoxoplasma therapy.
      DESIGN: A 15-month prospective multicentre cohort study in France. METHODS: One
      hundred and eighty-six consecutive HIV-positive inpatients undergoing empiric
      antitoxoplasma therapy for a first episode of presumed TE were monitored. The
      clinician's initial estimation of the probability of response to antitoxoplasma
      therapy was recorded. In addition, a validation committee classified cases as TE
      or non-TE. RESULTS: Among the 186 patients, the following variables were
      significantly more frequent in TE (n = 113) than non-TE (n = 73) patients: fever
      (59% versus 40%). headache (55% versus 33%), seizures (22% versus 11%),
      suggestive lesions on the brain scan (98% versus 76%), positive Toxoplasma
      serology (97% versus 71%). Median CD4+ lymphocyte count was significantly higher
      in TE than in non-TE (27 x 10(6)/l versus 11 x 10(6)/l). The rate of TE in
      patients on systemic antiprotozoal prophylaxis at entry was 43% as compared with
      75% in patients without previous prophylaxis. Pre-therapy estimation of response
      to empiric therapy was highly correlated with final diagnosis. Multivariate
      logistic regression analysis showed that the following variables contributed
      independently to the diagnosis of TE: clinician's estimation of response to
      treatment at entry > 75%; absence of systemic antiprotozoal prophylaxis;
      seizures; headache; suggestive lesions on CT or MRI brain scan; and positive
      Toxoplasma serology. CONCLUSIONS: A linear logistic model is proposed which uses
      significant variables, which are readily available. This model gives good
      accuracy to classify suspected cases of TE.

PMID- 9030365
TI  - Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with
      antiretroviral nucleoside analogues.
AB  - OBJECTIVE: A severe dose limiting axonal peripheral neuropathy may develop in
      subjects on treatment with the nucleoside analogues didanosine (ddl), zalcitabine
      (ddC), and stavudine (d4T). The impairment of mitrochondrial DNA synthesis is
      crucial to the pathogenesis of this disorder although other mechanisms have not
      been ruled out. The depletion of acetyl-carnitine, which regulates the metabolism
      and function of peripheral nerves could contribute to the neurotoxicity of these
      compounds. DESIGN: Non-randomized, cross-sectional study of selected patients.
      METHODS: We measured the serum levels of acetyl- and total carnitine in 12
      subjects with axonal peripheral neuropathy developed on treatment with different
      regimens of neurotoxic nucleoside analogues (ddl, ddC, d4T). Subjects who did not
      develop peripheral neuropathy while staying on treatment with ddl (n = 10) or
      zidovudine (n = 11) served as the control groups. HIV-negative subjects with
      axonal on demyelinating autoimmune neuropathies (n = 10) and healthy individuals
      (n = 13) were additional control groups. RESULTS: Subjects experiencing axonal
      peripheral neuropathy on treatment with ddl, ddC and d4T had significantly
      reduced levels of acetyl-carnitine in comparison to the control groups. No
      difference was observed in the levels of total carnitine between study subjects
      and the control groups. CONCLUSIONS: Our results demonstrate that subjects who
      developed peripheral neuropathy while staying on treatment with ddl, ddC and d4T
      had acetyl-carnitine deficiency. The normal levels of total carnitine in the
      study group appear to indicate the specificity of the defect and rule out
      coexisting relevant nutritional problems. The critical role of acetyl-carnitine
      for the metabolism and function of the peripheral nerves supports the view that
      the acetyl-carnitine deficiency found in these subjects may contribute to the
      neurotoxicity of ddl, ddC and d4T, even though the interference with
      mitochondrial DNA synthesis is regarded as the main cause of their toxicity.

PMID- 9030366
TI  - Sexual negotiation in the AIDS era: negotiated safety revisited.
AB  - OBJECTIVE: To test the safety of the 'negotiated safety' strategy-the strategy of
      dispensing with condoms within HIV-seronegative concordant regular sexual
      relationships under certain conditions. METHOD: Data from recently recruited
      cohort of homosexually active men (Sydney Men and Sexual Health cohort, n = 1037)
      are used to revisit negotiated safety. The men were surveyed using a structured
      questionnaire and questions addressing their sexual relationships and practice
      their own and their regular partner's serostatus, agreements entered into by the
      men concerning sexual practice within and outside their regular relationship, and
      contextual and demographic variables. RESULTS: The findings indicate that a
      significant number of men used negotiated safety as an HIV prevention strategy.
      In the 6 months prior to interview, of the 181 men in seroconcordant HIV-negative
      regular relationships, 62% had engaged in unprotected anal intercourse within
      their relationship, and 91% (165 men) had not engaged in unprotected anal
      intercourse outside their relationship. Of these 165 men, 82% had negotiated
      agreements about sex outside their relationship. The safety of negotiation was
      dependent not only on seroconcordance but also on the presence of an agreement;
      82% of the men who had not engaged in unprotected anal intercourse outside their
      regular relationship had entered into an agreement with their partner, whereas
      only 56% of those who had engaged in unprotected anal intercourse had an
      agreement. The safety of negotiation was also related to the nature of the safety
      agreement reached between the men and on the acceptability of condoms. Agreements
      between HIV-negative seroconcordant regular partners prohibiting anal intercourse
      with casual partners or any form of sex with a casual partner were typically
      complied with, and men who had such negotiated agreements were at low risk of HIV
      infection. CONCLUSIONS: The adoption of the strategy of negotiated safety among
      men in HIV-seronegative regular relationships may help such men sustain the
      safety of their sexual practice.

PMID- 9030368
TI  - Impact of HIV/AIDS on life expectancy in the United States.
AB  - OBJECTIVES: The potential gains in life expectancy of the US population by the
      partial and total elimination of deaths from HIV/AIDS were compared with that of
      deaths from heart disease and malignant neoplasms. METHODS: The data from the
      1992 advanced mortality report and detailed information provided by the National
      Center for Health Statistics were analysed by using the partial multiple
      decrement life-table technique. RESULTS: For the total population of the United
      States in 1992, the gains in future life expectancy through the elimination of
      deaths from HIV/AIDS, heart disease and malignant neoplasms were 0.34, 3.25 and
      3.21 years, respectively. The gains in life expectancy in those of working age 15
      64 years) through the elimination of deaths from these three causes of deaths
      were 0.20, 0.40 and 0.55 years, respectively. Race/sex-specific calculations
      indicate that the total elimination of deaths from HIV/AIDS, heart disease and
      malignant neoplasms in white men of working age resulted in increased life
      expectancy of 0.28, 0.54 and 0.53, respectively, whereas the corresponding
      figures for black men were 0.82, 0.90 and 0.76 years, respectively. Although the
      impact of the elimination of the other causes remained relatively stable from
      1987 to 1992, the potential gains in life expectancy for black men of working age
      by eliminating HIV/AIDS rose from 0.36 years in 1987 to 0.82 years in 1992. For
      the total US population of working age, the elimination of HIV/AIDS deaths
      resulted in increased life expectancy similar to that observed for a 50%
      reduction of heart disease or malignant neoplasms, whereas among black men of
      working age, the increased years of life expectancy from the elimination of
      HIV/AIDS deaths were virtually the same as those observed for the elimination of
      heart disease or malignant neoplasms. CONCLUSIONS: The potential gains in life
      expectancy by reduction of deaths from heart disease and malignant neoplasms are
      more heavily influenced by increasing years after the working ages (15-64 years),
      whereas the potential gains in life expectancy by reducing deaths from HIV/AIDS
      make a greater contribution to those of working age. Hence, in terms of the
      economic costs and benefits, these results indicate that in evaluating policy
      issues regarding allocation of research funds, studies of life expectancy are far
      more important than the simple approach which allocates funds on the basis of the
      number of deaths due to various diseases.

PMID- 9030367
TI  - Most HIV-1 genetic subtypes have entered Sweden.
AB  - OBJECTIVE: The aim of this study was to document which genetic subtypes of HIV-1
      have entered Sweden and to study transmission patterns of these virus variants.
      PATIENTS: All HIV-1 infected individuals at Danderyds Hospital, Stockholm,
      Sweden, who were suspected of carrying a virus of African origin were
      prospectively included in the study. The study subjects originated from 15
      different African countries. METHODS: The V3 domain of the HIV-1 envelope was
      directly sequenced from uncultured peripheral blood mononuclear cells from 75
      individuals included in the study. Phylogenetic analyses were used to determine
      genetic subtype and to study transmission patterns. RESULTS: The virus strains
      carried by the study subjects belonged to six established subtypes of HIV-1 (27A,
      4B, 18C, 18D, 2G, 2H). Two individuals from Zaire carried a subtype, which had
      not been classified previously, provisionally named subtype 1. Eleven
      transmissions of non-subtype B strains in Sweden were documented. CONCLUSIONS:
      This study shows that most genetic HIV-1 subtypes have entered Sweden despite the
      relatively low prevalence of HIV infection in the country. Thus, the complete
      dominance of subtype-B infections which was seen during the early phase of the
      HIV-1 epidemic in Europe and the US has been broken in Sweden.

PMID- 9030369
TI  - Long-term survival in patients with advanced immunodeficiency.
AB  - OBJECTIVE: To identity prognostic factors associated with survival time in HIV
      infected patients with advanced immunodeficiency. DESIGN: Prospective cohort
      study. PARTICIPANTS: A total of 1284 HIV-infected patients with serial CD4 count
      measurements and at least one CD4 cell count < or = 50 x 10(6)/I (CD4 < or = 50).
      MAIN OUTCOME MEASURE: Survival from initial CD4 cell count < or = 50 x 10(6)/l.
      RESULTS: The median survival from initial CD4 < or = 50 x 10(6)/l was 17.1
      months. The risk of death increased by 2% 195% confidence interval (Cl), 1-31 for
      each year of age, by 10% (95% Cl, 3-16) for each 10 x 10(6)/l decrease in CD4
      count, and by 14% (95% Cl, 9-18) for each 1 g/dl decrease in haemoglobin level.
      Compared to AIDS-free patients with CD4 < or = 50 x 10(6) cells/l, the risk of
      dying was 1.5-fold (95% Cl, 1.2-1.9) that of patients who had an AIDS diagnosis
      for fewer than 3 months prior to CD4 < or = 50, 1.8-fold for patients with an
      AIDS diagnosis for 4-11 months prior to CD4 < or = 50, and twice that of patients
      with AIDS for > or = 12 months prior to CD4 < or = 50. The risk of dying for
      patients whose rate of CD4 cell decline was > 40 x 10(6)/l per 6 months was 1.7
      fold (95% Cl, 1.3-2.3) that of patients with an average CD4 cell loss < 40 x
      10(6)/l per 6 months, after adjusting for age, haemoglobin and duration of AIDS
      prior to CD4 < or = 50 x 10(6) cells/l. A prognostic score was developed from the
      final multivariate model, based on age at CD4 < or = 50, haemoglobin at CD4 < or
      = 50, duration of AIDS and rate of CD4 decline prior to CD4 < or = 50.
      CONCLUSIONS: Routinely available clinical and laboratory data including
      haemoglobin level, rate of CD4 decline and duration of AIDS can be readily
      translated into a prognostic score and then used to predict the survival
      experience of an HIV-infected patient with advanced immunodeficiency.

PMID- 9030370
TI  - Dependence of the hazard of AIDS on markers.
AB  - OBJECTIVE: To investigate the dependence of the hazard of symptomatic AIDS on
      various markers using a non-parametric method. The markers we consider are
      measures of time (time since infection and calendar date), measures of immune
      function (numbers and percentage of CD4 T cells) and serological activation
      markers (neopterin and beta 2-microglobulin). METHODS: We adapted a non
      parametric statistical method to estimate the hazard of AIDS. We considered both
      univariate analyses, in which each marker was considered separately and bivariate
      analyses of pairs of markers. CONCLUSIONS: Using data from 356 seroconverters
      from the Multicenter AIDS Cohort Study, we found that in the univariate analyses
      the hazard of AIDS is dependent on all markers, with the strongest dependence for
      CD4 count and CD4 percentage. In the bivariate analyses we found that the time
      since infection is of little importance in determining the hazard of AIDS if the
      CD4 count or percentage are known, and is of minor additional value if one of the
      serological markers is known. In contrast, we found that both beta 2
      microglobulin and neopterin do add some additional information to the hazard of
      AIDS if CD4 count or CD4 percentage are known.

PMID- 9030371
TI  - Sex, drugs and HIV counseling and testing: a prospective study of behavior-change
      among methadone-maintenance clients in New England.
AB  - OBJECTIVES: To determine whether changes in injecting drug use and sexual
      behavior over a 12-month follow-up are associated with HIV counseling and testing
      (C and T) of injecting drug users in methadone maintenance treatment programs
      (MMTP) in Massachusetts and Connecticut. METHODS: Clients were invited to
      participate in a longitudinal study involving five interviews. Data were also
      obtained by ethnographers and from clinical records. Behavioral outcomes of
      interest were number of drug injections, sharing of unclean 'works' (injecting
      equipment), number of unprotected sex partners, and number of unprotected sexual
      episodes. Data analyses included multiple regression, odds ratios, and
      quantitative analysis of text-based data. RESULTS: Subjects reported reductions
      in both injecting drug use and sexual behavior Primary associations with reduced
      injecting drug use were remaining in the MMTP and attending HIV-positive support
      groups. A reduction in high-risk sexual behavior was associated with an HIV
      positive test result and duration of HIV counseling in the MMTP. Increase in drug
      injecting use was associated with an HIV-positive test result. Inconsistent
      condom use was associated with enrollment in the MMTP where condoms were
      available only upon request and abstinence and monogamy between uninfected
      partners were promoted. CONCLUSIONS: Injecting drug users who self-select to
      participate in MMTP and HIV C and T, two public health HIV-prevention
      interventions, reduce their HIV-risk behaviors. Clients should be encouraged to
      remain in MMTP and HIV-infected clients should attend support groups for HIV
      positive persons. MMTP staff should promote a variety of safer sex behaviors and
      provide condoms without request.

PMID- 9030372
TI  - Sexual behaviour patterns and other risk factors for HIV infection in rural
      Tanzania: a case-control study.
AB  - OBJECTIVE: To examine the association between HIV infection and patterns of
      sexual behaviour and other risk factors in a rural Tanzanian population in a case
      control study, nested within a randomized trial of improved sexually transmitted
      disease treatment. METHODS: All HIV-positive patients from the baseline survey of
      the randomized trial were eligible as cases. Cases (n = 338) and controls (a
      random sample of one in eight HIV-negative persons; n = 1078) were interviewed
      about risk factors for HIV infection using a structured questionnaire. RESULTS: A
      significantly higher HIV prevalence was found among men and women not currently
      employed in farming [men: odds ratio (OR), 2.08; women: OR, 3.65], women who had
      travelled (OR, 3.27), educated women (OR, 4.51), and widowed/ divorced people
      compared with those currently married (men: OR, 3.10; women: OR, 3.54). Two
      spouse-related factors were significantly associated with HIV, even after
      adjustment for the sexual behaviour of the index case: HIV was more prevalent in
      men with younger spouses (P = 0.020 for trend) and in women married to men
      currently employed in manual work, office work or business (OR, 2.20). In women
      only, blood transfusions were associated with a higher HIV prevalence (OR, 2.40),
      but only a small population attributable fraction (4%). There was an increased
      HIV prevalence associated with increasing numbers of injections. Reported number
      of lifetime sexual partners was significantly associated with HIV infection
      (women: OR, 7.33 if > or = 10 lifetime partners compared with < or = 1; men: OR,
      4.35 for > or = 50 compared with < or = 1). After adjustment for confounders,
      male circumcision was associated with a lower HIV prevalence (OR, 0.65; P =
      0.11). CONCLUSIONS: In these rural communities, many HIV infections occur through
      sexual transmission. Some people are at high risk of HIV infection through large
      numbers of sex partners, whereas some are at risk through their spouse or regular
      partner. The role of circumcision in HIV transmission is unclear. Commercial sex
      seems to play a negligible role in HIV transmission in these communities. Our
      results confirm marked heterogeneity in HIV risk, indicating the scope for risk
      reduction strategies.

PMID- 9030373
TI  - Human herpesvirus 8 in semen and prostate.

PMID- 9030374
TI  - Significance of restricted HIV expression for HIV neuropathogenesis: still an
      unresolved issue.

PMID- 9030375
TI  - No evidence of significant abortive HIV infection of the brain.

PMID- 9030376
TI  - Rhodococcus or mycobacterium? An example of misdiagnosis in HIV infection.

PMID- 9030377
TI  - Topical foscarnet for aciclovir-resistant mucocutaneous herpes infections in
      AIDS.

PMID- 9030378
TI  - Identification of Mycobacterium genavense in intestinal tissue from a parakeet
      using two polymerase chain reaction methods: are pets a reservoir of infection in
      AIDS patients?

PMID- 9030379
TI  - Macrophage inflammatory protein-1 alpha mRNA expression in mononuclear cells from
      different tissues during acute simian immunodeficiency virus strain mac251
      infection of macaques.

PMID- 9030380
TI  - Convenient twice daily foscarnet in induction therapy of AIDS-associated
      cytomegalovirus retinitis. The Foscarnet Italian Study Group.

PMID- 9030381
TI  - Solitary cutaneous cryptococcosis resembling chickenpox: a case report.

PMID- 9030382
TI  - Regression of AIDS-related Kaposi's sarcoma following treatment with an HIV-1
      protease inhibitor.

PMID- 9030383
TI  - Renal involvement in the diffuse infiltrative CD8 lymphocytosis syndrome.

PMID- 9030384
TI  - On returning for one's HIV test result: demographic, behavioral and psychological
      predictors.

PMID- 9030385
TI  - Focusing on the second phase of plasma HIV-1 RNA clearance.

PMID- 9030386
TI  - Disseminated granulomatous disease in a simian immunodeficiency virus- and
      bacille Calmette-Guerin-infected rhesus monkey.

PMID- 9030387
TI  - Rapid fatal evolution in two cases of infection due to HIV-1 uncommon subtypes in
      France.

PMID- 9030388
TI  - Saquinavir interaction with midazolam: pharmacokinetic considerations when
      prescribing protease inhibitors for patients with HIV disease.

PMID- 9030389
TI  - Absence of human herpesvirus 8 sequences in prostate specimens.

PMID- 9030390
TI  - Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V
      substitution in 3TC-resistant HIV-1 reverse transcriptase.
AB  - OBJECTIVE: To measure the extent of HIV resistance to (-)-2',3'-dideoxy-3'
      thiacytidine (3TC, lamivudine) within the context of monotherapy and to assess
      the presence of the M184V substitution in the case of 3TC-resistant viruses.
      Whether the success of 3TC in clinical trials could be due, in part, to an
      increase in the fidelity of HIV reverse transcriptase conferred by the M184V
      substitution was also considered. METHODS: Two separate monotherapy studies were
      evaluated, one involving adults with CD4 counts > or = 300 x 10(6)/l, and the
      second involving children, some of whom had received antiretroviral treatment
      previously, while others were drug naive. Peripheral blood and plasma samples
      were collected regularly, and HIV isolation and determinations of drug median
      inhibitory concentration values were performed using umbilical cord mononuclear
      cells as targets. Amplification of the 184 mutation was performed by the
      polymerase chain reaction, using specific primer pairs. Fidelity determinations
      using purified, recombinant HIV reverse transcriptase derived from either wild
      type virus or viruses that contained the 184V substitution were performed.
      RESULTS: Phenotypic resistance was detected in almost all subjects at times
      ranging from 8-20 weeks after initiation of therapy. The 184V substitution was
      usually detected prior to the occurrence of phenotypic resistance to 3TC.
      Fidelity determinations revealed that the 184V substitution conferred an
      approximately 5- to 10-fold increase in HIV reverse transcriptase fidelity. In
      addition, titres of patient sera tested for their ability to neutralize
      autologous sequential viral isolates were stabilized in patients receiving 3TC
      therapy as opposed to other drugs. CONCLUSIONS: Resistance to 3TC developed in
      virtually all subjects treated with this drug, and was associated with the
      appearance of an M184V mutation in HIV reverse transcriptase. The clinical
      benefit of 3TC therapy may be attributable in part to selection of viruses that
      are less able to replicate and mutate than the wild types.

PMID- 9030391
TI  - The treatment of antiretroviral-naive subjects with the 3TC/zidovudine
      combination: a review of North American (NUCA 3001) and European (NUCB 3001)
      trials.
AB  - OBJECTIVE: The compound (-)-2',3'-dideoxy-3'-thiacytidine (3TC, lamivudine) is a
      nucleoside analogue with potent in vitro antiretroviral activity, synergy with
      zidovudine, activity against zidovudine-resistant isolates and minimal
      cytotoxicity. In early-phase studies, 3TC had a favourable pharmacokinetic
      profile, was well tolerated by those with HIV infection, and had a modest effect
      on HIV-1 p24 antigen levels. Although resistance to 3TC monotherapy develops
      rapidly, the activity of the drug persists. However, zidovudine-resistant virus,
      in which the 3TC-resistance mutation is selected for, regains phenotypic
      sensitivity to zidovudine. Therefore, 3TC and zidovudine are a logical
      combination to evaluate as initial therapy in treatment-naive HIV-1 infected
      individuals. DESIGN: Two randomized controlled trials, one in Europe and one in
      North America, evaluated 3TC in combination with zidovudine and compared this
      combination to zidovudine monotherapy. In the North American study, 3TC
      monotherapy was also evaluated. In both studies, subjects entered having received
      less than 4 weeks of zidovudine therapy and no other previous antiretroviral
      treatments. In the European study, subjects had CD4 cell counts of 100-400/mm3
      and received blinded therapy for 24 weeks; they were then offered open-label 3TC
      and zidovudine for a further 24-week period. In the North American study, initial
      patient CD4 cell counts were 200-500/mm3, and blinded treatment continued for 52
      weeks. Endpoints measured included CD4 cell counts and HIV-1 RNA in plasma, in
      addition to clinical and laboratory adverse events. RESULTS: In both studies, the
      combination of 3TC and zidovudine resulted in rises in CD4 counts of 75-85
      cells/mm3 that were sustained at 48-60 cells/mm3 above base-line at 48-52 weeks.
      Effects on HIV-1 RNA levels in plasma also persisted through 48 and 52 weeks at
      approximately a 90% reduction (1 log10 decrease) from baseline. In the European
      study, the combination was superior to zidovudine alone over the first 24 weeks,
      as measured by CD4 and HIV-1 RNA effects, and the addition of 3TC to zidovudine
      after 24 weeks resulted in a subsequent increase in the mean CD4 count of 39
      cells/mm3. In the North American study, the combination of 3TC and zidovudine was
      better than zidovudine monotherapy when considering the effect on CD4 cells or
      HIV-1 RNA through 24 weeks. When these treatment groups were compared, using an
      average of the mean change from baseline of the CD4 counts and HIV-1 RNA levels
      over that last three study time points (44, 48 and 52 weeks), the combination
      treatments remained superior to zidovudine alone. In neither study did the
      addition of 3TC to zidovudine result in additional toxicity. SUMMARY: In two
      independent studies in patients with limited antiretroviral treatment experience,
      remarkably similar results were obtained when 3TC/zidovudine in combination was
      compared to zidovudine monotherapy, demonstrating sustained antiretroviral and
      immunological effects of the combination over the 48 and 52 weeks of study.

PMID- 9030392
TI  - The role of immunologic and viral markers in predicting clinical outcome in HIV
      infection.
AB  - OBJECTIVE: In an ideal world, one clinical marker would explain all the variance
      in a disease system. In reality, however, this is rarely the case and HIV disease
      is no exception. This review considers several specific markers that have
      demonstrated some use in clinical trials and/or epidemiologic studies of
      antiretroviral therapy. DISCUSSION: CD4 lymphocyte count, HIV viral load and
      perhaps immune activation markers can be used to measure the activity of
      antiretroviral therapy. Some recent studies are presented and the results
      discussed. CONCLUSION: Sustained improvements in several markers (particularly
      HIV viral load and CD4 cell count) in combination appear to be the most
      predictive of clinical benefit. No current viral or immunologic markers
      adequately reflect toxicities attributable to antiretroviral therapy.
      Lamivudine/zidovudine combination therapy leads to sustained changes in several
      markers, and appears to be well tolerated. This may translate into significant
      clinical benefit but the duration of such benefit remains unknown.

PMID- 9030393
TI  - Clinical significance of drug resistance in HIV-1 infection.
AB  - OVERVIEW: The limited duration of clinical benefit from nucleoside analogue
      therapy for HIV-1 infection may be explained, in part, by the emergence of virus
      isolates resistant to the drugs used. Additional reasons may include the presence
      of syncytium-inducing variants of HIV-1, progressive increase in viral load and
      progressive immunologic decline despite antiretroviral therapy. DISCUSSION:
      Antiretroviral therapy may inevitably select for mutational changes in HIV-1
      populations. However, recent advances in the understanding of drug resistance in
      HIV-1 infection suggest that, in certain cases, genotypic and phenotypic changes
      associated with drug resistance in vitro are not always synonymous with clinical
      drug failure. We consider the following examples: (1) the benefit of switching
      therapy may be independent of drug resistance; (2) patients may progress on
      therapy despite persistence of 'sensitive' virus; (3) drug susceptibility testing
      may underestimate the significance of drug resistance, and antiviral activity may
      persist despite resistance; and (4) resistance may be overcome with higher
      dosing. CONCLUSION: Laboratory evidence for drug resistance does not necessarily
      imply clinical drug failure. Emergence of (-)-2',3-d-deoxy-3'-thiacytidine (3TC,
      lamivudine) resistance may potentiate activity of zidovudine in patients treated
      with 3TC/zidovudine combination therapy. Novel therapeutic strategies that
      exploit this mutational interaction, or challenge the limits of adaptation of the
      virus, may lead to more effective long-term suppression of HIV-1.

PMID- 9030394
TI  - Selecting a model system for neurobiological studies of learning and memory.
AB  - This article discusses the logic underlying the use of invertebrate model systems
      for investigating the neurobiological basis of learning and memory, the kinds of
      questions which can be asked of these systems as well as their limitations. A
      model system selected to answer specific questions about learning and memory is
      most useful if its selection is based on strategy rather than chance.

PMID- 9030395
TI  - The effects of lesions to thalamic lateral internal medullary lamina and
      posterior nuclei on learning, memory and habituation in the rat.
AB  - The behavioral effects of radiofrequency lesions to the lateral internal
      medullary lamina region (IML) or the posterior region (Po: containing the
      parafascicular and posterior nuclei) of the thalamus were compared to sham
      operated controls. Subjects were pre-operatively trained and then tested for post
      operative retention of a NMTP task. Whereas the Po-lesion group was impaired only
      on long delays (60, 90 s), the IML-lesion group was impaired on retention and re
      acquisition and demonstrated lower performance at all delays (5-90 s) of the NMTP
      task. Post-operative training and testing was conducted on three additional
      tasks: Morris water maze, acoustic startle, and passive avoidance. The IML-lesion
      group was impaired in finding a hidden and visual platform in the Morris water
      maze, demonstrated a blunted response but normal habituation to an acoustic
      startle stimulus, and showed normal retention of a passive avoidance task. On
      those three tasks, the performance of the Po-lesion group was similar to
      controls. In the IML-lesion group, neuronal loss resulting from axotomy and/or
      transneuronal degeneration was observed within nuclei of the midline and anterior
      thalamus and the mammillary body. These results suggest that lesions to the IML
      region disrupt a range of cognitive functions and produce pathological
      destruction in distant brain regions; whereas damage to the posterior thalamus
      causes spatial delay-sensitive deficits.

PMID- 9030396
TI  - The effects of cooling the area postrema of male rats on conditioned taste
      aversions induced by LiC1 and apomorphine.
AB  - Although permanent lesion studies have demonstrated that the area postrema (AP),
      a chemoreceptor trigger zone, is part of the neural mechanism for conditioned
      taste aversions (CTAs), its exact role remains questionable. It has been
      suggested that the attenuated acquisition of a CTA after permanent lesions of the
      AP is the result of an inability to recognize the conditioned taste as novel. The
      present series of experiments was designed to test the hypothesis that lesions of
      the AP interfered with LiCl processing and not recognition of taste novelty. This
      was accomplished by using the reversible lesioning procedure, cooling, only
      during administration of the illness-inducing agent. In Expt. 1, measurement of
      thermal lines around the tip of the cold probe in the AP indicated that our
      cooling procedures allowed the majority of the AP to be cooled to temperatures
      that suppress neuronal activity and transsynaptic transmission, but not axonal
      transmission. In Expts. 2 and 3, rats were injected with either LiCl or
      apomorphine after consumption of a 10% sucrose solution. Cooling of the AP was
      initiated 5 min before administration of one of the illness-inducing agents and
      was continued for 55 min after injection. The rats were tested later for
      acquisition while the neural function of the AP was preserved. Our experimental
      results demonstrated that cooling the AP could attenuate the CTA induced by LiCl,
      but had no effect on the CTA induced by apomorphine. Since the AP was functional
      when the rats encountered the novel sucrose solution both before and after
      conditioning, but not functional when LiCl was given, these results do not
      support the recognition of taste novelty hypothesis.

PMID- 9030397
TI  - Task-involvement and ego-involvement goals during actual and imagined movements:
      their effects on cognitions and vegetative responses.
AB  - It has been experimentally proven many times that the mental rehearsal of an
      activity not only improves motor performance but also has vegetative effects
      whose magnitude is correlated with the amount of imagined effort. These
      beneficial effects of mental imagery have been explained in terms of central
      programming structures capable of anticipating the metabolic demands of the task.
      Twenty-four subjects were asked to actually perform and also imagine an isometric
      contraction of the forearm under various goal conditions: a task-involving goal
      (8 subjects), an ego-involving goal (8 subjects), and no goal (8 subjects).
      During the contractions, electromyographic potential and heart rate were
      measured. Afterwards, the subjects were asked to indicate the amount of effort
      expended under different feedback conditions. The results showed no trace of
      electromyographic activity during the imagined contractions when the lack of
      movement was controlled using a force sensor. On the other hand, a significantly
      faster in heart rate was observed with a task- or ego-involving goal than with no
      goal, during both actual and imagined contraction. Similarly, as predicted,
      subjects said they applied less effort in the positive feedback condition, and
      more effort in the negative feedback condition with an ego-involving goal. The
      results are discussed in the light of goal theories, while regarding goals not
      only as serving to anticipate metabolic expenditures but also as promoting a self
      image of competence, particularly in threatening, ego-involving situations.

PMID- 9030398
TI  - The nomadic engram: overtraining eliminates the impairment of discriminative
      avoidance behavior produced by limbic thalamic lesions.
AB  - Combined lesions of the medial dorsal and anterior thalamic nuclei severely
      impair the acquisition of discriminative avoidance behavior, wherein rabbits
      learn to prevent foot-shock by stepping after a tone conditional stimulus (CS+),
      and they learn to ignore a different tone (CS-) that does not signal foot-shock.
      Neurons in these thalamic nuclei exhibit training-induced firing pattern changes
      during behavioral acquisition to asymptotic performance levels. However, the
      changes decline in magnitude during the course of post-asymptotic training
      (overtraining), suggesting a declining participation of the thalamic neurons in
      task mediation. In order to test this hypothesis, electrolytic or sham limbic
      thalamic lesions were induced either immediately after asymptotic performance was
      reached, or after the administration of training to asymptote and ten additional
      overtraining sessions. Retention after the lesions was assessed using an
      extinction procedure (CS presentation without foot-shock) followed by re
      acquisition. Rabbits given lesions after criterion attainment exhibited a
      significant retention deficit during both the extinction and re-acquisition
      tests. However, no significant retention deficit was found in rabbits given 10
      days of overtraining prior to the lesions. These results support the prediction
      derived from the neuronal data, of a time-limited involvement of limbic thalamic
      neurons in mediation of discriminative avoidance behavior.

PMID- 9030399
TI  - Differential effects of communal rearing and preweaning handling on open-field
      behavior and hot-plate latencies in mice.
AB  - On day 2 after delivery, dams of the DBA/1 mouse inbred strain (n = 20/group)
      with their litter were allocated to one of the following groups: NH21,
      nonhandling, housed 1 litter/cage, weaned on postnatal day (PND) 21;H21,
      handling, housed 1 litter/cage, weaned on PND 21; NH30, nonhandling, group-housed
      (5 litters/cage), weaned on PND 30; H30, handling, group-housed (5 litters/cage),
      weaned on PND 30. Two male pups of each litter were color marked on PND 2. From
      PND 8-21 they were removed from their cage, gently held in the experimenter's
      hand for 5 min/day. The two marked males of each litter were housed together
      after weaning, and tested in the open-field on PNDs 51-53, and one of each of
      these siblings was tested for hot-plate latencies on PND 54. Being raised in
      group-housing and weaned on PND 30 resulted in offspring exhibiting shorter
      latencies to initiate behavior and higher percentages of centerfield entries in
      the open field, hot-plate latencies, however, remained unaffected. Preweaning
      handling increased hot-plate latencies and the number of grooming episodes in the
      open field, and it decreased defecation, percent centerfield entries and open
      field activity in general. It is concluded that the two forms of early experience
      have different effects on neurobehavioral endpoints 8 weeks after birth.

PMID- 9030400
TI  - Dose-related impairment of spatial learning by intrahippocampal scopolamine:
      antagonism by ondansetron, a 5-HT3 receptor antagonist.
AB  - To study the role of hippocampal muscarinic receptors in spatial learning,
      various doses of scopolamine were injected bilaterally into the CA1 region of the
      dorsal hippocampus of rats trained in a two-platform spatial discrimination task.
      Scopolamine administered 10 min before each training session at doses ranging
      from 3.75 to 15 micrograms/microliter impaired choice accuracy, had no effect on
      choice latency and increased the errors of omission only with 7.5 micrograms on
      day 1 and with 15 micrograms on days 1 and 2 of training. No dose affected choice
      accuracy or latency of a non-spatial visual discrimination task. A subcutaneous
      dose of 1 microgram/kg ondansetron, a 5-HT3 receptor antagonist, 30 min before
      each training session prevented the impairment of choice accuracy by
      intrahippocampal 3.75 micrograms scopolamine but 0.1 microgram/kg ondansetron had
      no such effect. No dose of ondansetron by itself modified the acquisition of
      spatial learning. The results suggest that relatively low doses of scopolamine in
      the dorsal hippocampus selectively impair the acquisition of a spatial
      discrimination task, and that blockade of 5-HT3 receptors prevents the deficit
      caused by the muscarinic antagonist. The utility of the deficit of spatial
      learning induced by intrahippocampal scopolamine for modelling some aspects of
      memory disturbances in Alzheimer's disease is discussed.

PMID- 9030401
TI  - Catechol O-methyltransferase inhibitor tolcapone has minor influence on
      performance in experimental memory models in rats.
AB  - Two catechol O-methyltransferase inhibitors, peripherally acting entacapone and
      also centrally acting tolcapone, were tested regarding their capacity to
      influence learning and memory in adult intact rats. Tolcapone was also studied in
      rats treated with scopolamine, in adult rats lesioned in the nuclei basalis
      magnocellularis, and in aged rats. Spatial working memory performance (radial-arm
      maze) of intact rats was facilitated following pretraining i.p. administration of
      tolcapone (10 mg/kg). Entacapone was ineffective at doses of 10 and 30 mg/kg.
      Senescent poor performers improved their accomplishment in the spatial memory
      task (linear-arm maze) under the influence of tolcapone. Scopolamine (1 mg/kg)
      impaired working memory performance. Bilateral lesions in the nucleus basalis
      magnocellularis reduced choline acetyltransferase activity in the frontal cortex
      by 26% and retarded the learning rate of spatial place task. Tolcapone was not
      able to counteract the performance deficits in these models. It is concluded that
      tolcapone can either slightly improve or impair the memory functions depending on
      task specific elements and performance factors.

PMID- 9030402
TI  - Opposite effects depending on learning and memory demands in dorsomedial
      prefrontal cortex lesioned rats performing an olfactory task.
AB  - In this study, the functional properties of the dorsomedial prefrontal cortex
      (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue
      olfactory discrimination task, dmPFC lesioned animals improved performance across
      sessions more rapidly than operated control animals. In an olfactory task using
      fixed interval training, animals with similar lesions were impaired. Both
      effects, although opposite, can be explained by a temporal processing deficit.
      The present results seem to indicate that the dmPFC is required for timing,
      classified as part of non-declarative memory. As reference memory improved in the
      lesioned animals, the finding is that the dmPFC supports non-declarative memory
      and thus interacts with declarative memory in the long-term formation of the
      associations between a particular stimulus (olfactory cue) and particular
      responses.

PMID- 9030403
TI  - Functional changes induced by neonatal cerebral 6-hydroxydopamine treatment:
      effects of dose levels on behavioral parameters.
AB  - Male Sprague-Dawley rats were treated neonatally with either of three different
      doses of 6-hydroxydopamine (6-OHDA): 50 micrograms i.c., 75 micrograms i.c., or 2
      x 100 micrograms i.c.v., 30 min after a subcutaneous injection of desipramine
      (DMI, 25 mg/kg), in order to obtain selective lesions of mesencephalic dopamine
      (DA) neurons to different extents. From juvenile ages onwards, rats in each dose
      condition were tested for spontaneous motor activity and exploration in an
      openfield/holeboard setting measuring ambulation, rearing and head-dips. Between
      77 and 78 days, the animals were tested in a modified, enclosed radial arm maze,
      followed 1 week later by tests in the circular swim maze. Finally, motor activity
      was tested in automated activity test chambers. In the openfield/holeboard
      setting, hyperactivity was seen for both rearing and ambulation in rats
      administered 50 micrograms 6-OHDA, whereas the 75 micrograms and 2 x 100
      micrograms groups showed hyperactivity for ambulation, but hypoactivity for
      rearing and head-dips. All three dose groups demonstrated a retardation of
      learning in the radial arm maze. The 75 and 2 x 100 micrograms groups, but not
      the 50 micrograms group, showed impairments of acquisition in the swim maze. In
      the activity test chambers locomotion and rearing behavior varied as a function
      of 6-OHDA dose, being negatively and positively, respectively, related to DA
      concentration in striatum. These results show that the extent of the neonatal DA
      lesion determines both changes in motor- and exploratory activity as well as the
      occurrence and severity of acquisition impairment in spatial learning tasks.

PMID- 9030404
TI  - Utilization of the Denny-Brown collection: differential recovery of forelimb and
      hind limb stepping after extensive unilateral cerebral lesions.
AB  - The Denny-Brown collection of primate lesion material was used to test the
      hypothesis that there is a difference in the rate of forelimb and hind limb
      recovery of locomotor movements after major unilateral cerebral ablation
      (pre/postcentral gyrus, decortication or hemispherectomy). The results indicate
      that, following major cerebral injury, hind limb recovery precedes that of the
      forelimb in adolescent and adult primates, but not in infants. This suggests that
      there is an underlying physiological basis to the widely-held belief that, in
      humans, lower limb recovery after stroke is generally more complete than that of
      the upper limb.

PMID- 9030405
TI  - The effects of gonadal steroids on brain stimulation reward in female rats.
AB  - The present study examined possible estrogen and/or progesterone effects on the
      mesolimbic dopamine (DA) system using brain stimulation reward (BSR). It is well
      known that BSR with electrical stimulation of the medial forebrain bundle (MFB)
      depends on the functioning of the mesolimbic DA system. If estrogen affects this
      system in a manner similar to its effects on the nigrostriatal DA system, reward
      measures would be expected to vary across the estrous cycle. Cycling female rats
      were trained to bar press for electrical stimulation to the MFB. Animals were
      tested at each stage of the estrous cycle, after ovariectomy and 4, 24, 48, 72
      and 96 h after hormone replacement with estradiol (10 micrograms, s.c.),
      estradiol and progesterone (0.5 mg, s.c.), or oil (s.c.). The rewarding value of
      the stimulation and the maximum rate of bar pressing increased during estrus, but
      not during proestrus or metestrus, as compared with diestrus. Hormone replacement
      had differing effects on reward and motor performance. Motor performance
      increased 4 and 24 h after estrogen alone and 24 h after estrogen with the
      addition of progesterone 4 h before testing. The rewarding value of the
      stimulation increased only 24 h after estrogen together with an injection of
      progesterone 4 h before testing. These results indicate that gonadal steroids
      affect the functioning of the mesolimbic DA system.

PMID- 9030406
TI  - Aminopeptidase A antiserum inhibits intracerebroventricular angiotensin II
      induced dipsogenic and pressor responses.
AB  - Angiotensin II increases drinking and blood pressure when administered
      intracerebroventricularly. Intracerebroventricular injections of antiserum with
      anticatalytic activity against aminopeptidase A, the principal enzyme that
      metabolizes angiotensin II to angiotensin III, reduced the drinking and blood
      pressure responses to 10 pmol angiotensin II by 73% and 59%, respectively. APA
      antiserum had no effect on responses to angiotensin III administered
      intracerebroventricularly. A Glu-thiol inhibitor of aminopeptidase A also reduced
      angiotensin II-induced drinking. These results suggest that metabolism of
      angiotensin II to angiotensin III is an obligatory activation step for the brain
      angiotensin system.

PMID- 9030407
TI  - Aggregates of a beta-amyloid peptide are required to induce calcium currents in
      neuron-like human teratocarcinoma cells: relation to Alzheimer's disease.
AB  - We report that human hNT cells display neuron-like calcium channel activation.
      Patch-clamp experiments show that exposure of hNT cells to the Alzheimer-related
      amyloid peptide beta AP(25-35) induces large and irreversible inward calcium
      currents at -80 mV in whole cell mode, with a linear current-voltage
      relationship. This behavior is suggestive of ionophore formation. An analogous
      peptide with scrambled sequence has no effect. These ionophore effects by the
      beta AP(25-35) peptide, the first report in a human cell-line, are very rapid
      effects. The currents are large and stable, and are blocked by Al3+ but not by
      Cd2+. Filtration removes a peptide aggregate from the amyloid peptide beta AP(25
      35) solution and thereby abolishes the inward current. The residual soluble
      peptide has no effect. These data suggest that the initial step of the neurotoxic
      effect of beta AP(25-35) may be due to the insertion of the aggregated peptide
      into the cellular membrane as a Ca2(+)-carrying ionophore. The relevance of
      calcium-mediated cell death, especially in Alzheimer's disease, is discussed.

PMID- 9030408
TI  - Role of the central amygdala in social communication in Syrian hamsters
      (Mesocricetus auratus).
AB  - In Syrian hamsters, vasopressin (AVP) controls a form of scent marking called
      flank marking. Microinjection and lesion studies have identified several
      components of the neural circuit controlling this behavior. Microinjection of AVP
      into the medial preoptic-anterior hypothalamus (MPOA-AH), lateral septal nucleus
      (LS), bed nucleus of stria terminalis (BNST), and periaqueductal gray (PAG)
      stimulates an intense bout of flank marking. Lesions of areas such as the MPOA-AH
      and the LS inhibit flank marking. Other studies employing Fos immunocytochemistry
      suggest that the central amygdala (Ce) might be a component of this neural
      circuit. The purpose of the present study was to assess the significance of the
      Ce in regulation of AVP-induced flank marking. In Expt. 1A, the Ce of hamsters
      were either lesioned with ibotenic acid or sham-lesioned. In Expt. 1B, the Ce of
      hamsters were either lesioned electrolytically or sham-lesioned. All lesions were
      made bilaterally. One week later, hamsters were microinjected with AVP into the
      MPOA-AH and immediately tested for flank marking. In Expt. 2, the hamsters were
      microinjected with AVP into the Ce and were immediately tested for flank marking.
      Ibotenic lesions of the Ce reduced flank marking and electrolytic lesions
      completely inhibited flank marking in response to AVP microinjected into the MPOA
      AH. Sham-lesions or lesions placed in other areas of the amygdala resulted in
      intense bouts of AVP-induced flank marking and flank grooming. No flank marking
      or flank grooming was observed in response to AVP microinjected into the Ce.
      These data indicate that the Ce plays a critical role in AVP-induced flank
      marking, although flank marking is not induced by AVP within the Ce itself.

PMID- 9030409
TI  - Somatosensory evoked magnetic fields arising from sources in the human
      cerebellum.
AB  - Somatosensory evoked neuromagnetic activity of human cerebellum was recorded
      noninvasively with a 122-channel whole-scalp magnetometer. Cerebellar source
      areas activated 13-19 ms after unilateral electric stimulation of the median
      nerve. The first signals preceded those occurring in the primary sensorimotor
      cortex at around 20 ms and overlapped in time with the activation of thalamic
      sources. The orientation and location of most prominent cerebellar activation
      suggest that the detected signals represent synchronized postsynaptic activity of
      spinocerebellar cortex. These signals are probably elicited by the first afferent
      sensory volley from peripheral nerve endings and mediated by spinocerebellar
      (cuneocerebellar) tracts. The results imply strong coherent activation of
      cerebellar neuronal populations after purely sensory stimulation. Moreover, with
      presented methods the millisecond-scale temporal resolution of neurophysiological
      measurements can be more generally applied to the study of neuronal population
      activity in intact human cerebellum.

PMID- 9030410
TI  - Delay in simple reaction time after focal transcranial magnetic stimulation of
      the human brain occurs at the final motor output stage.
AB  - It is known that the execution of the motor response in a simple reaction time
      (RT) task can be delayed by transcranial magnetic stimulation (TMS). This paper
      is aimed at determining the site of action where the delay in RT occurs. A delay
      in RT was obtained only at those TMS sites over the motor cortex contralateral to
      the responding hand, which produced also a muscle twitch in the responding hand.
      The delay in RT covaried with the TMS intensity and increased the closer the time
      of TMS approached the expected time of reaction onset. Visual and auditory go
      signals yielded similar delays in RT, but only when TMS was applied about 40 ms
      later for the visual go-signal, corresponding to the modality specific difference
      in RT control values. TMS of the supplementary motor area (SMA) immediately prior
      to the expected time of reaction onset produced no delay in RT. Spinal
      excitability as tested by F waves showed a pre-movement facilitation in the
      control trials which continued seemingly undisturbed during the period of RT
      delay after TMS. It can be concluded that the delay in RT is not due to SMA
      stimulation or spinal inhibition but depends on effective stimulation of neural
      elements in the motor cortex which are active very late in the process of
      movement release from the final motor output stage.

PMID- 9030411
TI  - Pharmacological characterization of buprenorphine, a mixed agonist-antagonist
      with kappa 3 analgesia.
AB  - Buprenorphine is a mixed opioid agonist/antagonist analgesic. This study was
      designed to determine the role of opioid receptor subtypes, especially kappa 3,
      in buprenorphine-induced analgesia in mice. Buprenorphine, when injected
      systemically, revealed a potent analgesic effect by tailflick assay, with a
      biphasic dose-response curve, which was reversed by naloxone. The presence of
      analgesic cross-tolerance between buprenorphine and naloxone benzoylhydrazone
      (NalBzoH) and morphine indicated a role for kappa 3 and mu receptor subtype in
      buprenorphine analgesia. Additional studies with selective opioid antagonists
      indicated kappa 1 mechanisms of action. We did not detect any involvement of the
      delta receptor subtype. Low doses of buprenorphine antagonized morphine
      analgesia, while high doses of buprenorphine coadministered with morphine
      elicited increasing analgesia in a dose-dependent manner. These findings suggest
      that buprenorphine elicits analgesia through an interaction with kappa 3
      receptors and to a lesser extent with kappa 1 as well as its activity as partial
      mu receptor agonist.

PMID- 9030412
TI  - Localization of calcium receptor mRNA in the adult rat central nervous system by
      in situ hybridization.
AB  - The capacity to sense changes in the concentrations of extracellular ions is an
      important function in several cell types. For example, hormone secretion by
      parathyroid cells and thyroid C-cells is primarily regulated by the level of
      extracellular ionized calcium (Ca2+). The G-protein-coupled receptor that
      mediates the parathyroid cell response to Ca2+ has been cloned and we have used
      in situ hybridization to map calcium receptor (CaR) mRNA expression in the adult
      rat brain. Cells expressing CaR mRNA were present in many areas of the brain
      suggesting that a variety of cell types express the CaR. Particularly high
      numbers of CaR expressing cells were found in regions associated with the
      regulation of fluid and mineral homeostasis, most notably the subfornical organ.
      These data suggest that the capacity to detect changes in extracellular Ca2+
      concentrations may have important functional consequences in several neural
      systems.

PMID- 9030413
TI  - Metabolic and pathological effects of temporal lobe epilepsy in rat brain
      detected by proton spectroscopy and imaging.
AB  - The goal of these experiments was to test the hypothesis that in an animal model
      of temporal lobe epilepsy (TLE), magnetic resonance spectroscopic measurement of
      N-acetylaspartate (NAA) and other metabolites, together with magnetic resonance
      imaging, provides a sensitive in vivo method to localize and monitor the
      progression of neuronal cell death and gliosis. Seizures were induced in rats by
      unilateral hippocampal injection of kainate. Magnetic resonance measurements were
      made from 1 to 84 days using proton spectroscopic imaging (1H-MRSI), T2-weighted
      imaging (T2WI) and diffusion-weighted imaging (DWI). The results were compared
      with findings on histological sections. Decreased NAA and creatine levels and
      increased apparent diffusion coefficient of water were found in the ipsilateral
      hippocampus after 14 days where neuronal loss and gliosis were observed. In the
      contralateral hippocampus a significant increase of choline level was observed.
      These results suggest that 1H-MRSI is a useful in vivo method for localizing
      neuronal loss and may also indicate additional pathological and metabolic
      alterations. In addition, DWI may be a useful method for in vivo detection of
      tissue alterations due to TLE.

PMID- 9030414
TI  - Calcium oscillations in a subpopulation of S-antigen-immunoreactive pinealocytes
      of the rainbow trout (Oncorhynchus mykiss).
AB  - By means of the fura-2 technique and image analysis the intracellular
      concentration of free calcium ions [Ca2+]i was examined in isolated rainbow trout
      pinealocytes identified by S-antigen immunocytochemistry. Approximately 30% of
      the pinealocytes exhibited spontaneous [Ca2+]i oscillations whose frequency
      differed from cell to cell. Neither illumination with bright light nor dark
      adaptation of the cells had an apparent effect on the oscillations. Removal of
      extracellular Ca2+ or application of 10 microM nifedipine caused a reversible
      breakdown of the [Ca2+]i oscillations. Application of 60 mM KCl elevated [Ca2+]i
      in 90% of the oscillating and 50% of the non-oscillating pinealocytes. The effect
      of KCl was blocked by 50 microM nifedipine. These results suggest that voltage
      gated L-type calcium channels play a major role in the regulation of [Ca2+]i in
      trout pinealocytes. Experiments with thapsigargin (2 microM) revealed the
      presence of intracellular calcium stores in 80% of the trout pinealocytes, but
      their role for regulation of [Ca2+]i remains elusive. Treatment with
      norepinephrine (100 pM-50 microM), previously shown to induce calcium release
      from intracellular calcium stores in rat pinealocytes, had no apparent effect on
      [Ca2+]i in any trout pinealocyte. This finding conforms to the concept that
      noradrenergic mechanisms are not involved in signal transduction in the directly
      light-sensitive pineal organ of anamniotic vertebrates.

PMID- 9030415
TI  - Pineal metabolic reaction to retinal photostimulation in ganglionectomized rats.
AB  - The aim of the present work was to test the pineal gland metabolic reactivity to
      nocturnal retinal short term photic stimulation in superior cervical
      ganglionectomized rats. The experimental support for this work is the appearance
      of a transitory post synaptic hyperactivity in the pineal gland, during the
      anterograde degenerating process of the conarii sympathetic nerve fibers after
      surgical removal of the cell body. In this situation the pineal gland is
      deafferented from the peripheral sympathetic nervous system keeping intact,
      however, the direct central connections to the deep pineal/lamina intercalaris
      region (DP). The results show a blockade of the pineal noradrenergic stimulatory
      process due to the retinal photostimulation. The inactivation of N
      acetyltransferase led to a true metabolic shift to the oxidative pathway
      resulting in a decrease of the amount of N-acetylserotonin and an increase of the
      amount of serotonin, 5-hydroxyindoleacetic acid and 5-hydroxytryptophan. This
      inhibitory process brought into action by retinal illumination is dependent on
      the direct central neural connections to the pineal gland, since rats that were
      lesioned in the DP, previously to ganglionectomy, did not show any alteration on
      the indolic content of the pineal gland when subjected to nocturnal retinal
      photostimulation.

PMID- 9030416
TI  - Role of arginine vasopressin and corticotropin-releasing factor in mediating
      alcohol-induced adrenocorticotropin and vasopressin secretion in male rats
      bearing lesions of the paraventricular nuclei.
AB  - In male rats, lesions of the paraventricular nucleus (PVN) of the hypothalamus
      attenuate, but do not abolish, adrenocorticotropin (ACTH) secretion in response
      to acute alcohol injection. As the PVN is the major source of corticotropin
      releasing factor (CRF) in the median eminence, this observation suggests that
      extra-PVN brain regions, and/or ACTH secretagogues other than CRF (e.g. arginine
      vasopressin (AVP)), mediate ACTH stimulation by alcohol. This hypothesis was
      tested by examining the effect of AVP immunoneutralization in PVN-lesioned (PVNx)
      rats. Removal of endogenous AVP diminished alcohol-evoked ACTH secretion in both
      sham-operated and PVNx animals, indicating that AVP from outside the PVN
      partially mediates the hypothalamic-pituitary-adrenal (HPA) axis response to
      alcohol. This led us to determine whether alcohol might also regulate AVP steady
      state gene expression in the supraoptic nucleus (SON) and PVN, and/or CRF mRNA in
      the PVN and the central nucleus of the amygdala (AMY). In the magnocellular
      portion of the PVN, sham-operated animals showed significantly increased PVN
      levels of both CRF and AVP mRNAs 3 h after alcohol. In the SON, alcohol
      administration tended to decrease AVP gene expression in PVNx rats, while the
      drug increased AVP mRNA levels in the SON of sham-operated rats. AMY levels of
      CRF mRNA were unaffected by these manipulations. Finally, since the regulation of
      alcohol-induced AVP mRNA levels in the SON appeared to depend on the presence of
      the PVN, we measured peripheral levels of AVP in both sham-operated and PVNx
      animals after injection of vehicle or alcohol. Although AVP decreased in all
      groups, alcohol depressed AVP secretion to a greater extent in PVNx animals,
      suggesting that AVP systems are more sensitive to inhibition in the absence of
      the PVN. Our results demonstrate that although AVP of PVN origin may participate
      in regulating the stimulatory effect to AVP on ACTH secretion, AVP from areas
      other than the PVN also plays a role. Additionally, regulation of both AVP gene
      expression in the SON and secretion in the systemic circulation are altered in
      rats bearing lesions of the PVN.

PMID- 9030417
TI  - Alpha-adrenergic receptor antagonism and N-methyl-D-aspartate (NMDA) induced
      luteinizing hormone release in female rhesus macaques.
AB  - The stimulatory influence of N-methyl-D-aspartate (NMDA), a glutamate receptor
      agonist, on LH secretion is well established in several mammalian species
      including the rhesus macaque. Although the mechanism of excitation appears to
      involve enhanced GnRH secretion, it is unclear whether the GnRH neurons respond
      directly to this excitation or whether stimulatory inter-neurons are involved.
      This study investigated the possibility that noradrenergic afferents play a major
      role in mediating the response of the primate hypothalamo-pituitary reproductive
      axis to NMDA. In situ hybridization histochemistry, using a cRNA probe coding for
      the NMDAR1 receptor subunit, revealed abundant mRNA in the locus coeruleus, a
      brain area rich in noradrenergic neurons. Furthermore, using double-label
      fluorescence immunocytochemistry, the tyrosine hydroxylase immunopositive neurons
      of the locus coeruleus showed immunoreactivity for the NMDAR1 receptor subunit
      protein. A second experiment examined whether prazosin, an alpha 1-adrenergic
      receptor antagonist, could attenuate NMDA-induced stimulation of LH release.
      Prazosin (either 1 or 5 mg/kg b.wt., i.v.) was administered to female rhesus
      macaques during the luteal phase of the menstrual cycle, 40 min before
      administration of NMDA (10 mg/kg b.wt., i.v.). Regardless of the prazosin pre
      treatment, plasma LH concentrations showed a significant increase (P < 0.01)
      within 10 min of the administration of NMDA. Therefore, in spite of the evidence
      that at least some of the noradrenergic neurons of the primate hindbrain express
      the NMDAR1 receptor subunit, it is unlikely that noradrenergic inter-neuronal
      pathways alone play a major role in mediating the stimulatory action of NMDA on
      GnRH/LH secretion in primates. Indeed, because the GnRH neurons of the rhesus
      macaque are located diffusely in various regions of the hypothalamus and medial
      septal/preoptic area, their net response to excitatory amino acids is likely to
      be more complicated, involving a combination of both stimulatory and inhibitory
      inter-neurons, and possibly also a direct interaction.

PMID- 9030418
TI  - Brain lactate, not glucose, fuels the recovery of synaptic function from hypoxia
      upon reoxygenation: an in vitro study.
AB  - Lactate has been considered for many years to be a useless, and frequently,
      harmful end-product of anaerobic glycolysis. In the present in vitro study,
      lactate-supplied rat hippocampal slices showed a significantly higher degree of
      recovery of synaptic function after a short hypoxic period than slices supplied
      with an equicaloric amount of glucose. More importantly, all slices in which
      anaerobic lactate production was enhanced by pre-hypoxia glucose overload
      exhibited functional recovery after a prolonged hypoxia. An 80% recovery of
      synaptic function was observed even when glucose utilization was blocked with 2
      deoxy-D-glucose during the later part of the hypoxic period and during
      reoxygenation. In contrast, slices in which anaerobic lactate production was
      blocked during the initial stages of hypoxia did not recover their synaptic
      function upon reoxygenation despite the abundance of glucose and the removal of 2
      deoxy-D-glucose. Thus, for brain tissue to show functional recovery after
      prolonged period of hypoxia, the aerobic utilization of lactate as an energy
      substrate is mandatory.

PMID- 9030419
TI  - Neurons co-localizing calretinin immunoreactivity and reduced nicotinamide
      adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the hippocampus
      and dentate gyrus of the rat.
AB  - Co-localization of calretinin immunoreactivity and nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) activity was studied in the rat
      hippocampus and dentate gyrus. Neurons co-expressing both markers (CR/NADPH-d)
      were observed throughout the hippocampus and dentate gyrus. However, they were
      more abundant in the stratum pyramidale and radiatum of CA3, stratum pyramidale
      of CA1, and in the juxtagranular zone of the hilus. The NADPH-d activity appeared
      in 37% of the calretinin immunoreactive neurons in CA3, 42% in CA1, and 36% in
      the dentate gyrus, whereas calretinin immunoreactivity occurred in 41% of the
      NADPH-d positive neurons in the hippocampus, and 16% in the dentate gyrus. The
      morphology and location of the double marked cells could not be used as a
      characteristic of the co-localizing neurons. The heavily stained NADPH-d neurons
      occurring mainly in CA1 do not show calretinin immunoreactivity. NADPH-d fiber
      swellings could be observed in close apposition to calretinin immunoreactive
      neurons and dendrites, suggesting synaptic contacts. It has been reported that
      calretinin immunoreactivity and NADPH-d activity co-localize infrequently in
      other areas such as the neocortex, striatum, hypothalamus and tegmental nucleus.
      The relatively high proportion of double marked cells found in the hippocampus
      and dentate gyrus could be indicative of the importance of the CR/NADPH-d
      interneurons in the circuitries of these areas.

PMID- 9030420
TI  - Stimulus-response functions in areas with experimentally induced referred muscle
      pain--a psychophysical study.
AB  - Few clinical or experimental studies have carried out systematic investigations
      of cutaneous and deep sensibility in areas with referred muscle pain. Therefore,
      no clear signs of increased or decreased psychophysical responses to various
      somatosensory stimuli are found in referred pain areas. In the present study, a
      total of 7.1 ml 5% hypertonic saline was infused over 900 s into the m. tibialis
      anterior of 11 subjects. This produced local muscle pain and pain referred to the
      ventral aspect of the ankle. A continuous recording of the ongoing pain
      intensities of the local and referred pain was carried out on two electronic
      visual analogue scales (VAS). Before, during and 30 min after the period with
      referred pain, radiant heat (argon laser) stimuli, single and repeated electrical
      stimuli, and pressure stimuli were applied to the referred pain area. Stimulus
      response (SR) functions were obtained by means of pain intensity ratings of the
      different stimuli at 75%, 112.5% and 150% of the individual pain threshold (PT)
      intensity. The pain intensities of contact heat (thermode) stimuli at 40 degrees
      C, 47 degrees C and 50 degrees C and pin-prick stimuli with von Frey hair were
      also assessed in the referred pain area. The saline-induced local muscle pain
      intensity was higher than the intensity of the referred pain (P < 0.05). The
      referred pain intensity was significantly higher in the 20-460 s interval than in
      the 460-900 s interval (P < 0.05). This difference was not seen for the local
      muscle pain. During the period with referred pain, significantly decreased
      responses to radiant heat and pressure stimuli were found at 112.5% and 150% of
      PT intensity (P < 0.05). Further, significantly increased responses to single and
      repeated electrical stimuli at 75% and 112.5% of PT intensity (P < 0.05) were
      also found. After the period with referred pain, a considerably decreased
      response to single and repeated, electrical stimuli (P < 0.05) was present
      together with significantly increased responses to contact heat stimuli at 40
      degrees C and radiant heat stimuli at 75% of PT intensity (P < 0.05). The present
      results suggest that ongoing muscle pain can cause modality-specific (and bi
      directional) sensory changes in the referred pain area. This could explain why
      previous studies have reported both decreased and increased responses in referred
      pain areas.

PMID- 9030421
TI  - Localization of the glutamate transporter protein GLAST in rat retina.
AB  - Glutamate is a neurotransmitter in retina. Glutamate transporter proteins keep
      the resting extracellular glutamate concentration low. This is required for
      normal neurotransmission and prevents the extracellular concentration of
      glutamate from reaching toxic levels. Here we describe the light and electron
      microscopic localization of the glutamate transporter protein GLAST in rat retina
      using an antibody raised and affinity purified against a peptide corresponding to
      amino acid residues 522-541. The strongest immunocytochemical labelling was
      observed in the outer plexiform layer, ganglion cell layer, and optic disc. GLAST
      was found in Muller cell processes in all retinal layers, notably ensheathing the
      photoreceptor terminals in the outer plexiform layer, and in astrocytes close to
      vessels in the inner retina and optic disc. No labelling was observed in neurons.
      The electrophoretic mobility of GLAST in retina was similar to that in
      cerebellum. In conclusion, the findings are in agreement with those reported by
      Derouiche and Rauen [7], except that we did not detect any GLAST in the retinal
      pigment epithelium.

PMID- 9030422
TI  - Glucose-6-phosphate dehydrogenase activity is higher in the olfactory bulb than
      in other brain areas.
AB  - The activity of antioxidant enzymes was measured in the olfactory bulb (OB) of
      rat and compared with cortex, hippocampus, striatum and septum. Glutathione
      reductase, glutathione peroxidase, catalase and superoxide dismutase were not
      significantly different in the five brain areas, while glucose-6-phosphate
      dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase activities were four
      times higher in the OB than in the other areas. This picture prompted us to
      explore the reasons of the marked increase of G6PD, since it is the enzyme that
      regulates the operation of the hexose monophosphate shunt. A first approach was
      to analyze the G6PD electrophoretic pattern. The analysis revealed that the high
      G6PD activity of the bulb was neither due to new isoenzymes nor to a modification
      of the equilibrium between the G6PD dimers. We secondly hypothesized an induction
      of G6PD activity in the OB by oxidant stress. The assay of markers of the oxidant
      stress, such as thiobarbituric acid reactive substances, oxidized and reduced
      glutathione, did not confirm this hypothesis. A third approach was the
      cytochemical analysis of cryostat sections of OB. By this method we identified a
      particular cell type which was very rich in G6PD and located at the border of the
      glomerular layer. Thus, we attributed the high G6PD activity of the OB to the
      consistent presence of periglomerular cells, that probably need a high G6PD
      activity for their regulatory function in the neurochemical transmission.

PMID- 9030423
TI  - Region specific mitochondrial gene expression in the human retina.
AB  - The human mitochondrial genome has not been previously known to differentially
      express specific mRNA transcripts. Results of northern analysis, using total RNA
      from two different retinal regions, demonstrate that there is differential
      expression of five mitochondrial genes. There is a correlation of regional
      expression of one of these differentially expressed genes with the gene
      responsible for the majority of cases of foveo-macular mitochondropathy. These
      findings suggest that there is selective control over specific mitochondrial
      messenger steady state levels.

PMID- 9030424
TI  - Evidence for facilitation of motor evoked potentials (MEPs) induced by motor
      imagery.
AB  - This study examined the extent to which motor imagery can facilitate to specific
      pools of motoneurons. Motor commands induced by motor imagery were subthreshold
      for muscle activity and were presumably not associated with any change in
      background afferent activity. To estimate excitability changes of flexor carpi
      radialis (FCR) muscle motoneuron in spinal and cortical level, electric stimuli
      for recording H-reflex and transcranial magnetic stimulation (TMS) for recording
      motor evoked potentials (MEPs) were used. During motor imagery of wrist flexion,
      remarkable increases in the amplitude of the MEP of FCR were observed with no
      change in the H-reflex. Furthermore, facilitation of antagonist (extensor carpi
      radialis; ECR) was also observed. Therefore, it is concluded that internal motor
      command can activate precisely cortical excitability with no change in spinal
      level without recourse to afferent feedback.

PMID- 9030425
TI  - Arginine and NADPH diaphorase in the rat ventroposterior thalamic nucleus.
AB  - Simultaneous immunocytochemical staining for arginine (Arg) and histochemical
      staining for reduced nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPHd, a marker for nitric oxide synthase) reveals that neuropil in the
      ventroposterior nucleus of the thalamus is enriched with both Arg-positive glial
      profiles and NADPHd-positive fibers. NADPHd-positive fibers are often apposed to
      Arg-positive astrocytes and oligodendrocytes. NADPHd-positive endothelial cells
      are often adjacent to Arg-positive astrocytes. The results suggest that Arg may
      be stored in supporting cells, whence it could be supplied to nearby nerve fibers
      or endothelial cells as substrate for nitric oxide synthase.

PMID- 9030426
TI  - Evidence for N-methyl-D-aspartate receptor-mediated increase in norepinephrine
      utilization in the prefrontal cortex of unanesthetized rats.
AB  - Local injection of N-methyl-D-aspartate (NMDA; 10-20 nmol/rat) into the
      prefrontal cortex of conscious rats caused a dose-related and an NMDA antagonist
      reversible facilitation of norepinephrine (NE) disappearance in the cortical
      region during 35 min after inhibition of tyrosine hydroxylase. Destruction of
      ascending NE neurons by bilateral application of 6-hydroxydopamine into the
      superior cerebellar peduncle failed to affect [3H]N-(1-[2
      thienyl]cyclohexyl)piperidine binding to the NMDA receptor-associated ion channel
      in the prefrontal cortex. These results indicate that, under unanesthetized
      conditions, the prefrontal NE neurons may be under glutamatergic facilitatory
      control mediated by the NMDA receptors which are located on the non-NE systems in
      the frontal cortex.

PMID- 9030427
TI  - Alterations in N-methyl-D-aspartate receptor binding in dystonic hamster brains.
AB  - The genetically dystonic hamster is an animal model of idiopathic dystonia that
      displays sustained abnormal movements and postures either spontaneously or in
      response to mild environmental stimuli. Previous pharmacological studies have
      shown that competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor
      antagonists exert potent antidystonic activity in this model, indicating that
      abnormal NMDA receptor function may be involved in the pathophysiology of this
      movement disorder. Autoradiographic analysis of NMDA receptor density in 67 brain
      regions, using the ligand [3H] N-(1-[2-thienyl]cyclohexyl)3,4-piperidine, which
      binds to the phencyclidine (PCP) site in the ion channel of the NMDA receptor
      channel complex, revealed that NMDA receptor binding is not substantially altered
      in dystonic hamster brains compared to age-matched controls. Nevertheless, there
      was a tendency towards enhanced binding during a dystonic attack in several
      regions, including a 25% increase in the ventrolateral thalamic nucleus (P <
      0.05), which may be associated with altered basal ganglia output. While the data
      do not indicate widespread abnormalities in the PCP site of the NMDA complex,
      they do not exclude the possibility of more pronounced changes at other
      regulatory binding sites of the NMDA complex or other types of glutamate
      receptors in dystonia.

PMID- 9030428
TI  - Astressin, a novel and potent CRF antagonist, is neuroprotective in the
      hippocampus when administered after a seizure.
AB  - Corticotropin-releasing factor (CRF), the principle hypothalamic regulator of the
      adrenocortical axis, also functions as a neurotransmitter. In this latter role,
      CRF causes electrophysiological activation and epileptiform activity in various
      brain regions. That finding, coupled with the observation that CRF mRNA is
      induced in endangered brain regions following necrotic insults, suggests that the
      peptide might contribute to necrotic neuron loss. Supporting that, a number of
      studies have shown that CRF antagonists decrease ischemic or excitotoxic damage
      to neurons. In the present report, we demonstrate the considerable
      neuroprotective potential of a novel and potent CRF antagonist, astressin,
      against kainic acid-induced excitotoxic seizures. Intracerebroventricular
      infusion of the peptide both 30 min before and 10 min after seizures decreased
      damage in some hippocampal cell fields by as much as 84%, a magnitude of
      protection greater than reported for other CRF antagonists against other models
      of necrotic neuronal injury. Administration of astressin was done against both
      local microinfusion (0.035 microgram) or systemic infusion (10 mg/kg body weight)
      of the excitotoxin; furthermore, the peptide protected even if administered only
      10 min following excitotoxin exposure. This fulfills a critical prerequisite for
      any eventual therapeutic use of CRF antagonists, namely that they need not be
      administered in anticipation of a neurological insult.

PMID- 9030429
TI  - Differential role of dopamine receptors on motor asymmetries of nigro-striatal
      lesioned animals that are REM sleep deprived.
AB  - Recently, we have shown that rapid eye movement sleep deprivation (REM-SD) in
      animals with lesions of the nigro-striatal pathway facilitates turning behavior
      and such increase still occurred even in the presence of dopaminergic grafts. The
      objective of this work was to determine which DA receptors are preferentially
      involved. The results showed that the D2 receptor antagonist sulpiride decreases
      significantly turning behavior of lesioned animals, with no effect whatsoever of
      the D1 antagonist SCH 23390. When lesioned animals were REM sleep deprived, the
      D1 but not the D2 receptor antagonist prevented the increase of turning induced
      by REM-SD. This work suggests that the increase of post-synaptic supersensitivity
      induced by REM-SD in nigro-striatal lesioned animals is mediated by D1 receptors.

PMID- 9030430
TI  - Stimulation of group III and IV afferent nerves from the hindlimb by thromboxane
      A2.
AB  - These experiments were designed to test the hypothesis that the TxA2 mimetic,
      U46,619, would stimulate group III and IV afferent nerve endings from the
      hindlimb of the anesthetized cat. Nerve impulses were recorded from the dorsal
      rootlets of the L7-S1 segments of the spinal cord, and afferent units identified
      by measurement of conduction velocities, mechanical probing of hindlimb muscles,
      and local injection of chemical stimulants (capsaicin and bradykinin). Five of
      the 15 group III fibers were stimulated by U46,619 (2-10 micrograms injected into
      the abdominal aorta; mean baseline impulse frequency increasing from 7.3 (+/-
      3.2) impulses/s to 16.0 (+/- 3.1)), while 7 of the 12 group IV fibers responded
      to U46,619 (impulse frequency increasing from 4.3 (+/- 3.2) to 8.8 (+/- 3.6)).
      The average latency for the response (20-30 s) did not differ between the two
      groups of afferent fibers. We conclude that group III and IV afferent fibers
      originating from the skeletal muscle of the hindlimb are stimulated by TxA2 and
      that the release of TxA2 in skeletal muscle could evoke cardiorespiratory
      reflexes known to be activated by stimulation of these afferent nerves.

PMID- 9030431
TI  - Vasoactive intestinal polypeptide containing neurones in monkey medial prefrontal
      cortex (mPFC): colocalisation with calretinin.
AB  - Neurones immunoreactive for vasoactive intestinal polypeptide (VIP) were studied
      in monkey medial prefrontal cortex. The majority (78.0%) of VIP+ neurones were
      bipolar cells located mainly in layers 2/3. Calretinin (CR) immunoreactivity was
      colocalised in 80.5% of VIP+ neurones. Furthermore, VIP+ puncta formed
      pericellular baskets around GABA immunonegative somata in layers 2/3. These
      results indicate that VIP/CR are colocalised in some bipolar cells and
      superficial pyramidal somata are likely targets of VIP+ neurones.

PMID- 9030432
TI  - Down-regulation of striatal enkephalinergic (PPA) messenger RNA without prior
      apoptotic features following reversible focal ischemia in rat.
AB  - In order to determine whether striatal enkephalinergic neurons were affected by
      reversible focal ischemia, we have investigated the expression of the
      preproenkephalin (PPA) messenger by in situ hybridization (ISH) combined with
      TUNEL staining to display apoptosis in the same rat brain sections. Our data
      demonstrated a massive reduction of the number of PPA-mRNA containing neurons
      concomitant with the emergence of apoptotic cells. However, double-labeled
      neurons (ISH- and TUNEL-positive cells) were not detected, suggesting that either
      disruption of mRNA precedes DNA fragmentation or ischemia leads to a long lasting
      reduction of mRNA(s) without damage.

PMID- 9030444
TI  - A personal revolution in the development of clubfoot correction.
AB  - This article presents the author's experience of having worked in London,
      England, under Denis Browne, whose method of treating equinovarus in the newborn
      involved manipulation of the baby feet until full correction had been achieved at
      the very first visit. The feet were then strapped to the sole plates of the Denis
      Browne splint, which ensured that the baby's normal kicking action maintained
      mobility at the subtalar joints and also a basic plantigrade posture. When he
      transferred to India, the author found a large population of children who had
      been born with talipes equinovarus, but who had never had treatment. He worked at
      obtaining correction without strong manipulation, using serial plaster casting
      followed by Denis Browne's splints. His personal reactions to the problems and
      the merits of the two methods forms the subject of this article.

PMID- 9030445
TI  - Congenital idiopathic talipes equinovarus (clubfoot). Current concepts.
AB  - Congenital idiopathic talipes equinovarus (clubfoot) is a complex and challenging
      entity. This article reviews its history, incidence, and classification as well
      as the current controversies regarding its causes, pathologic anatomy, evaluation
      and diagnostic techniques, surgical intervention, and treatment assessment
      methods.

PMID- 9030446
TI  - Evaluation and management of in-toe gait in the neurologically intact child.
AB  - A review of the nature, cause, natural history, and measurement of torsional
      problems of the lower extremity has been presented. A focused discussion of the
      often ignored consequences of residual torsions and the compensations for them
      when they are present has been included. Finally, current thought on management
      principles and techniques has been reviewed.

PMID- 9030447
TI  - Subtalar arthrorisis and associated procedures.
AB  - Not all flatfeet require surgical correction. Through a careful history obtained
      from the child's parents, useful clues may be gathered pertaining to the
      disability arising from the flatfoot. There are three distinct classifications of
      flexible pes pronatus that require specific procedures for correction of the
      primary deformity. The STA-Peg, alone or in combination with other medial arch
      procedures, is used for correction of hindfoot pronation in the coronal planar
      dominant foot. The postoperative disability associated with the STA-Peg is
      relatively minimal, and complications are usually due to improper insertion of
      the implant.

PMID- 9030448
TI  - Rehabilitation medicine approach to Charcot-Marie-Tooth disease.
AB  - Hereditary motor sensory neuropathies (HSMN) encompass a wide range of related
      neuromuscular disorders. Electrodiagnostic studies are a powerful tool in
      differentiating between the different types. Timely rehabilitative treatment of
      the deformities may result in significant functional improvement and delay or
      obviate need for future surgery. This article outlines types of HSMN, focusing on
      the electrodiagnosis and treatment of each.

PMID- 9030449
TI  - Evaluation of the child with ligamentous laxity.
AB  - Many opportunities for participation in the care of children with ligamentous
      laxity have been described in this article. The podiatric physician must
      determine his or her contribution based on knowledge, experience, and interest.
      Each podiatric physician is not necessarily expected to be familiar with all of
      the diseases and treatments described here. Novice podiatrists should be mandated
      to recognize only the presence of ligamentous laxity and be familiar with an
      appropriate referral pattern. In addition to the previously listed podiatric
      concerns, Hobson has described some specific concerns in even the most basic
      podiatric treatment. He recommends the use of skin adherents to avoid wrinkling
      and tearing the skin of individuals with Ehlers-Danlos syndrome. He also
      reiterates research that has determined a resistance to local anesthetics in
      these individuals. He further provides some detail for the manufacture of
      appropriate orthoses. Continuing education may be obtained through a variety of
      sources. These may include not only traditional podiatric courses and
      conferences, but also similar venues offered by clinicians in other specialties.
      Also, courses and conferences held by organizations with a special interest in
      these unusual disorders can be educational and rewarding. The author has found
      interactions with this patient population rewarding. The patients and their
      families are often exceptionally knowledgeable regarding their illness because
      most have experienced many years with unsatisfactory medical help and delayed or
      incorrect diagnoses. Most of these families are also extraordinarily grateful for
      the concern and interest expressed by the clinician. They are particularly
      impressed when the health care professional has at least a cursory knowledge of
      their unusual disorder. As a member of the Ehlers-Danlos National Foundation
      Medical Advisors Panel, the author has contact with world-renowned geneticists,
      rheumatologists, and other specialists. The leader of the organization has
      pointed out that patients have found that podiatric clinics provided during the
      national meetings are often one of the most appreciated aspects of those
      meetings. He stated that although podiatrists may not cure the disease, small
      improvements in the everyday lives of these patients add up to a significant
      contribution. The author hopes that this article will stimulate further interests
      in the care and understanding of individuals with ligamentous laxity. It is
      further hoped that experience with these individuals will translate to the
      broader population who experience milder disorders of hypermobility.

PMID- 9030450
TI  - Sedation, analgesia, and anesthesia issues in the pediatric patient.
AB  - Pediatric and adolescent patients facing analgesia, anesthesia, and surgical
      procedures require different considerations than adults do. The preoperative,
      intraoperative, and postoperative time periods are discussed. Analgesia
      considerations outside the operating room are covered. The practicing podiatric
      physician will be able to assess better the physical needs of the pediatric
      patient by understanding and incorporating their emotional needs.

PMID- 9030451
TI  - Usefulness of preoperative testing in pediatric podiatric surgery. Does it
      influence clinical decisions?
AB  - This article discusses the changing approach to preoperative laboratory testing
      in healthy children undergoing foot and ankle surgery from the economic as well
      as the medico-legal perspectives. The author then reviews the laboratory findings
      for 203 children, discusses the number and types of abnormalities encountered,
      and defines their impact on decision making in the perioperative period. Based on
      these experiences, recommendations on appropriate testing for these patients are
      made.

PMID- 9030453
TI  - Shoe therapy. Past and present treatments.

PMID- 9030452
TI  - Hip instability encountered in pediatric podiatry practice.
AB  - Infants and children with pathologic conditions of the foot and leg frequently
      have predictable comorbidity. The treating physician has the responsibility for
      identifying these associated problems and promptly referring if the problem is
      outside of his or her area of expertise. Hip dysplasia and dislocation occur
      frequently enough in association with congenital foot and leg deformity that they
      must be actively sought out in all cases. This article presents an overview of
      the topic, a review of screening protocols and appropriate imaging techniques and
      case studies of children with hip instability encountered in pediatric podiatry
      practice.

PMID- 9030454
TI  - Pediatric lower extremity splinting and bracing techniques.
AB  - Pediatric splinting and bracing techniques may be effectively used in the
      treatment of lower extremity rotational deformities. Early diagnosis coupled with
      the timely implementation of these techniques allows the practitioner to enhance
      normal development of the pediatric patient's lower extremities.

PMID- 9030455
TI  - Common problems in pediatric gastroenterology.

PMID- 9030456
TI  - Diagnosing otitis media: a workshop.

PMID- 9030457
TI  - Streptococcal pharyngitis: is penicillin still the right choice?

PMID- 9030458
TI  - Congenital & acquired cytopenias of infancy & childhood.

PMID- 9030459
TI  - Adolescent psychiatric conditions.

PMID- 9030460
TI  - Advice for selected breast-feeding issues.

PMID- 9030461
TI  - Current concepts in the management of pharyngitis.

PMID- 9030462
TI  - Adolescents with psychosomatic problems.

PMID- 9030463
TI  - Cholesterol in adolescents: whom to screen & how to treat.

PMID- 9030464
TI  - Thymus-derived peptides for chronic viral hepatitis: have they fulfilled their
      promise?

PMID- 9030465
TI  - Gastrin and colon cancer: a unifying hypothesis.
AB  - Recently, a variety of studies in vivo as well as in vitro have demonstrated that
      gastrointestinal hormones can influence the rate of proliferation of neoplastic
      cells. The widespread use of omeprazole, which increases serum gastrin, coupled
      with the findings that omeprazole causes gastric carcinoid tumors in rats and
      that a significant number of patients with adenocarcinoma of the colon have
      increased serum gastrin have focussed attention on the relationship between
      gastrin and colon cancer. In the present paper, we have reviewed the experimental
      findings in humans, experimental animals, and colon cancer cells in tissue
      culture that bear on the possible relationships between gastrin and colon cancer.
      Based on these findings, we have proposed two hypotheses that can account for the
      increased serum gastrin that occurs in some patients with colon cancer.

PMID- 9030466
TI  - Enteroscopy in patients with gastrointestinal bleeding of obscure origin.
AB  - Approximately 5% of all patients with gastrointestinal hemorrhage will not have a
      bleeding site found after standard evaluation with upper endoscopy and
      colonoscopy. The source of bleeding in these patients is often the small
      intestine. In the past 2 decades, our ability to examine the small bowel
      endoscopically has been enhanced by the use of intraoperative enteroscopy and the
      development of push and sonde enteroscopes. In a stepwise evaluation of the
      patient with obscure gastrointestinal bleeding using enteroscopy, the
      identification of a bleeding source has been reported in 70-100% of patients,
      usually leading to palliative, if not definitive, therapy. In this review we
      discuss the indications, methods and yields of each of these procedures, and
      propose a diagnostic algorithm with which to approach these patients.

PMID- 9030467
TI  - Suction sclerotherapy for the treatment of esophageal varices: a report of a
      preliminary feasibility study.
AB  - We report a new treatment modality for esophageal varices, suction sclerotherapy,
      which was designed to lift away mucosa and submucosa during treatment to prevent
      deep injection and resultant esophageal ulcerations. In order to compare the
      posttreatment complications of suction sclerotherapy against freehand
      sclerotherapy, we randomized 4 mongrel dogs to receive ten injections of 0.5-ml
      aliquots of absolute alcohol into the esophagus by either the suction or freehand
      sclerotherapy technique. The animals were humanely sacrificed after 48 h and
      examined. A total of five large, deep, confluent ulcers, free perforation, and
      lung abscess were seen in the animals randomized to freehand sclerotherapy. In
      contrast, a total of 14 shallow, discrete, erythematous lesions were found in the
      suction sclerotherapy group; none of these lesions extended deeper than the
      submucosa. We conclude that suction sclerotherapy produced local complications
      limited to the submucosa which were less severe as compared with freehand
      sclerotherapy.

PMID- 9030468
TI  - Thymus-derived peptides in the treatment of viral chronic hepatitis.
AB  - The immune system plays a crucial role in the control and eventual clearance of
      hepatitis B virus (HBV) infection. Immune mechanisms are now believed to
      participate in the pathogenesis of the hepatitis C virus (HCV) and to account
      perhaps for the high frequency of progression from acute to chronic disease.
      Although IFN-alpha has been proven effective in the treatment of viral chronic
      hepatitis B and C, response rates are low, reactivation of disease is appreciable
      and side effects of treatment are frequent. Both antiviral and immune modulatory
      activity have been ascribed to IFN-alpha and are believed to account for its
      therapeutic effect. Immune-active peptides including those derived from the
      thymus have also been evaluated over the past 15 years for the treatment of viral
      chronic hepatitis. This review summarizes clinical studies and experimental
      observations which provide the rationale for the use of these agents in the
      treatment of chronic hepatitis associated with HBV and HCV. Primary attention is
      focused on thymosin-alpha (T alpha 1), a synthetic peptide, which has been
      evaluated in clinical trials. T alpha 1 has in vivo and in vitro immune
      modulatory activity on lymphoid populations as well as the potential of more
      direct antiviral activity. Preliminary results of clinical trials utilizing
      combinations of T alpha 1 with various IFN preparations are also reviewed.

PMID- 9030469
TI  - Endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is a useful adjunct to
      laparoscopic cholecystectomy. Preoperative ERCP is indicated if there is a high
      degree of suspicion for common duct stones, when severe gallstone-induced
      pancreatitis is present, or when there is uncertainty regarding the diagnosis.
      The best indicators of common duct stones preoperatively are an elevated
      bilirubin, a dilated common bile duct (CBD) on sonography, or stones visualized
      in the CBD on sonography. Mild gallstone pancreatitis and transient mild
      elevations in liver enzymes are not predictive of CBD stones and are not
      indications for ERCP. Postoperative ERCP is highly effective in clearing CBD
      stones. It has the advantage of being more readily available as compared to
      laparoscopic CBD exploration, and preserves all the advantages of the
      laparoscopic approach. Post-operative ERCP is indicated for retained CBD stones,
      evaluation and therapy of biliary injuries, and persistent biliary symptoms or
      abnormal liver enzymes and bilirubin. ERCP is the procedure of choice for the
      evaluation of laparoscopic biliary injuries. Major biliary injuries will
      generally require surgical therapy. Bile duct strictures are sometimes amenable
      to endoscopic therapy with dilation and stents. Biliary leaks are readily
      treatable with endoscopic therapy. Small cystic duct stump leaks and leaks from a
      duct of Lushka close within a few days with nasobiliary drainage. Larger leaks
      may require more prolonged drainage with stents and early supplemental
      percutaneous drainage of an accompanying biloma. Bilious ascites should be
      treated with nasobiliary drainage using low suction to be prevent contamination
      of the peritoneal cavity with intestinal flora, and simultaneous percutaneous
      ascites drainage. Biliary leaks, unless associated with major bile duct injuries,
      rarely require surgical therapy.

PMID- 9030470
TI  - Mesenteric vein thrombosis. Four cases and review of the literature.
AB  - Mesenteric vein thrombosis, an uncommon but important clinical entity, can cause
      ischemia or infarction of the small intestine. Mesenteric vein thrombosis was
      first described nearly a century ago, but diagnosis remains difficult because it
      can affect young individuals without any known predisposing disorder and because
      patients often present with nonspecific abdominal symptoms. We report 4 cases of
      small intestinal ischemia secondary to superior mesenteric vein thrombosis. Three
      were due to hypercoagulable states (protein-S deficiency, factor-VII
      abnormalities) and one was idiopathic. In recent years, the development of modern
      imaging techniques (particularly ultrasonography, duplex scanning, and computed
      tomography) have enabled early recognition of this disease. Anticoagulation is
      therapeutic acutely unless there are signs of peritonitis which necessitate
      surgical resection of the infarcted bowel.

PMID- 9030471
TI  - Ultrasound bone densitometry of os calcis in elderly Japanese women with hip
      fracture.
AB  - We evaluated 138 elderly patients (mean age 79 years) within 2 weeks after hip
      fracture (67 cervical and 71 trochanteric) using an Achilles ultrasound bone
      densitometer (Lunar Corporation, Madison, WI). The ultrasound variables of speed
      of sound (SOS in m/second), broadband ultrasound attenuation (BUA in dB/MHz), and
      stiffness (%) index were measured on the os calcis. Ultrasound densitometry also
      was done on 563 normal postmenopausal women to assess normal age changes. An
      elderly subgroup (n = 138) served as age-matched controls for the hip fracture
      group. Further subgroups of 33 patients and 33 controls were compared for lumbar
      spine and femoral neck BMD. There were no statistically significant differences
      between the hip fracture group and age-matched controls in height and weight, but
      each ultrasound variable was significantly lower for the hip fracture group (P <
      0.0001). For the hip fracture group, SOS was 1470 +/- 19 m/second, BUA was 84.3
      +/- 8.4 dB/MHz, and the stiffness index was 47.8 +/- 9.2%, whereas for the age
      matched controls, SOS was 1486 +/- 27 m/second, BUA was 94.0 +/- 11.4 dB/MHz, and
      the stiffness index was 59.1 +/- 12.5%. There were no significant differences
      between cervical and trochanteric hip fracture groups. Logistic regression
      analysis showed that a change of the ultrasound values by 1 standard deviation
      (SD) changed the odds ratio for SOS, BUA, and stiffness index by 2.51, 3.24, and
      3.60, respectively. Ultrasound variables, particularly stiffness, were good
      indicators of hip fracture risk.

PMID- 9030472
TI  - Magnification error of femoral geometry using fan beam densitometers.
AB  - Hip axis length (HAL) has been reported as an independent risk factor for hip
      fracture. DEXA machines using fan beam techniques have become increasingly
      available. Errors in calculated hip axis length may be expected because of
      different degrees of magnification by the fan beam. The magnitude of this error
      on measurement of hip geometry was studied, using an anthropomorphic femur
      phantom with both fan beam (Lunar Expert and Hologic QDR-2000) and pencil beam
      (Lunar DPXL) densitometers. The clinical relevance of these findings was also
      examined using patient measurements of buttock soft tissue thickness. Femoral
      neck axis length (FNAL), which correlates well with HAL, was used as a
      measurement of hip geometry. There was a linear increase or decrease of FNAL with
      increasing distance of the phantom above the scanning table, when measured with
      the Lunar Expert or Hologic QDR-2000, respectively. There was no significant
      difference in FNAL at different heights using the pencil beam densitometer. The
      maximal difference in buttock soft tissue thickness in 30 women studied was 8.7
      cm. From the equations, derived from the phantom studies, this difference would
      result in an 8.2% (1.4 SD) increase, or an 11.4% (1.9 SD) decrease in FNAL in the
      largest woman as compared with the smallest woman when measured using the Lunar
      Expert or Hologic QDR-2000, respectively. We conclude that there may be
      unpredictable degrees of magnification of FNAL in vivo, caused by differences in
      buttock thickness, when measured using a fan beam densitometers. Until these
      problems are resolved. FNAL, or related parameters of femoral geometry, should be
      measured using pencil beam instruments.

PMID- 9030473
TI  - Discrimination of spinal fracture with various bone mineral measurements.
AB  - For several different bone mineral measurements and various skeletal sites, we
      compared capability to discriminate between women in various age decades with and
      without spinal fracture, and attempted to identify the most effective cutoff
      level in discrimination of spinal fracture. The subjects were 88 women aged 50-59
      years (including 32 with fracture), 95 women aged 60-69 years (including 54 with
      fracture), and 34 women aged 70-79 years (including 18 with fracture). Spinal
      trabecular and cortical bone mineral density (BMD) were measured using
      quantitative computed tomography (CT), and spinal, radial (ultra-distal, 10%
      distal and 33% distal), and calcaneal BMD were measured by dual X-ray
      absorptiometry. These BMD values were obtained in each subject on the same day.
      Three statistical techniques-Student's t-test, the logistic regression analysis,
      and the receiver operating characteristics (ROC) analysis- were applied and
      accuracy was calculated using the various cutoff values. The capability to
      discriminate between women with and those without fracture using these BMD values
      was different among the three age groups. In women aged 50-59 and 60-69 years,
      all measurements showed good capabilities for discriminating women with fracture.
      In women aged 70-79 years, these measurements showed lower capability than in
      those aged 50-59 and 60-69 years, but among them, the calcaneal and ultradistal
      radial BMD showed relatively good capability. The 10% and 33% distal radial BMD
      values were not useful in the detection of the high risk women with fracture. The
      cutoff BMD values for discrimination of women with fracture varied according to
      the sites and methods of measurement. For each specific age group, the most
      suitable measurement methods and the appropriate skeletal sites should be
      considered, and the effective cutoff values to discriminate those with fracture
      may differ according to the measurement methods, the skeletal sites examined, and
      age.

PMID- 9030474
TI  - Effects of moderate endurance exercise on calcium, parathyroid hormone, and
      markers of bone metabolism in young women.
AB  - We investigated the short-term (1 hour-3 days) effects of a 45 minute run on
      calcium, parathyroid hormone, the carboxyterminal propeptide of type I
      procollagen (PICP), and the immunoactive carboxyterminal telopeptide of type I
      collagen in serum (ICTP) in young females. Fourteen healthy young women, aged
      25.2 +/- 0.6 years (mean +/- SEM) with regular menstruations, participated. The
      test was outdoor jogging for 45 minutes at an intensity of 50% of VO2 max. Blood
      samples were collected 15 minutes before the test and 1, 24, and 72 hours after
      the test. The measured values were adjusted for changes in plasma volume. A
      significant decrease of ionized calcium was observed at 1 hour (P < 0.001) and 72
      hours (P < 0.05) and a significant increase of parathyroid hormone (PTH) was
      noted 24 (P < 0.01) and 72 hours (P < 0.05) after the test. A significant
      decrease of PICP at 1 hour (P < 0.05) was followed by an increase after 24 (P <
      0.01) and 72 hours (P < 0.001) and a significant increase in ICTP was noted at 24
      and 72 hours (P < 0.05). A strong positive correlation was found between serum
      levels of PICP and ICTP (r = 0. 55-0.84; P < 0.05) throughout the experiment. In
      conclusion, young females showed biochemical signs of increased bone collagen
      turnover and altered homeostasis of calcium and PTH after a single bout of
      moderate endurance exercise.

PMID- 9030475
TI  - Ultrasound velocity and broadband attenuation as predictors of load-bearing
      capacities of human calcanei.
AB  - The main purpose of this study was to determine whether calcaneal ultrasound
      parameters, measured in the mediolateral direction, reflect load-bearing
      capacities of human calcanei. Broadband ultrasound attenuation (BUA) and
      ultrasound velocity (UV) were measured in 20 cadaveric calcanei with a mean age
      of 74.1 (SD 8.8). Normalized BUA (nBUA) was determined by dividing BUA by the
      calcaneal thickness obtained using a pulse-echo technique. The bone mineral
      density (BMD) of each calcaneus was measured by quantitative computed tomography.
      The calcanei were embedded in PMMA to simulate the midstance physiologic
      orientation during compressive testing in the load-bearing direction. The failure
      load, stiffness, and energy absorption were determined for each calcaneus. It was
      shown that BMD was well correlated with all ultrasound parameters (P < 0.0001).
      BMD, BUA, nBUA, and UV were all significantly associated with calcaneal failure
      load, stiffness, and energy absorption capacity (P < 0.05). nBUA was found to be
      the strongest predictor of all compressive properties. BUA and BMD demonstrated
      similar predictability of stiffness and energy absorption capacity, however, BUA
      showed a more significant relationship to the failure load of the calcaneus than
      did BMD. UV was found to be inferior to BMD, as well as BUA or nBUA, in assessing
      failure load, stiffness, and energy absorption capacity. It was also shown that
      nBUA was superior to BUA in the assessment of load-bearing capacity, but not in
      the prediction of BMD. Multivariate regression analysis showed that the
      combination of BUA or nBUA with UV did not improve the predictability of failure
      load, stiffness, and energy absorption capacity over that of BUA or nBUA alone (P
      > 0.5).

PMID- 9030476
TI  - Comparison of the ability of recombinant human parathyroid hormone, rhPTH-(1-84),
      and hPTH-(1-31)NH2 to stimulate femoral trabecular bone growth in ovariectomized
      rats.
AB  - A recombinant human parathyroid hormone, rhPTH-(1-84), which is currently in
      Phase II clinical trial, and hPTH-(1-31)NH2 (Ostabolin) are promising anabolic
      agents for treating osteoporosis because they can stimulate cortical and
      trabecular bone growth in osteopenic, ovariectomized (OVX) rats and in
      osteoporotic, postmenopausal women when injected subcutaneously and
      intermittently at low doses. We have now found that, despite their different
      sizes and signaling properties (rhPTH-(1-84) stimulates adenylyl cyclase and
      phospholipase C; hPTH-(1-31)NH2 only stimulates adenylyl cyclase), they are
      equally osteogenic in OVX rats. Thus daily subcutaneous injections of 0.6
      nmol/100 g of body weight of rhPTH-(1-84) or hPTH-(1-31)NH2 into 3-month-old OVX
      rats for 6 weeks starting 2 weeks after OVX equally reduced the otherwise large
      OVX-triggered loss of femoral trabecular bone. Daily subcutaneous injections of
      0. 4 or 0.8 nmol/100 g of body weight of the two agents for 6 weeks also equally
      increased the mean thickness of the remaining femoral trabeculae in 3-month-old
      and 1-year-old OVX rats to 20 to 80% above the value in normal animals when
      started 9 weeks after ovariectomy.

PMID- 9030477
TI  - A new fluorometric assay for determination of osteoblastic proliferation: effects
      of glucocorticoids and insulin-like growth factor-I.
AB  - A novel fluorometric proliferation assay, AlamarBlue (AB), was used to study the
      proliferative capacity of isolated human osteoblasts (hOBs). AB is an oxidation
      reduction indicator that yields a fluorescent signal in response to metabolic
      activity. The assay was performed by replacing the experiment media in a
      microtiter plate with a 10% AB solution and measuring fluorescence after a 3-8
      hour incubation. The assay was optimized with respect to incubation time, cell
      density, and AB concentration. When the results of the AB assay were compared
      with cell counting in a Burker chamber there were consistently good correlations
      (r > 0.9), regardless of the agonist with which the cells were treated. The mean
      intraassay coefficient of variance (CV) values were 9.9-11.8% in experiments
      where osteoblasts were treated for 12 days with insulin-like growth factor-I (IGF
      I; 100 nM), or dexamethasone (1 micro;M). IGF-I dose dependently, at and above 1
      nM, stimulated proliferation of hOBs. This effect was detectable after 3 days and
      reached 130-140% of untreated controls after 12 days in culture. The effects of
      dexamethasone (DEX) on the proliferation rate of hOBs were more complex. In short
      term cultures, 3 days, DEX dose dependently stimulated proliferation. However, at
      and above 6 days, DEX exerted a biphasic effect, with stimulation seen at 1-10 nM
      and a marked inhibition of cell proliferation at and above 100 nM. dexamethasone,
      hydrocortisone, prednisolone, and deflazacort had almost identical biphasic
      effects on osteoblastic proliferation in 12 day cultures with a stimulation seen
      at 1-10 nM, and a marked inhibition down to 50-60% of untreated controls at and
      above 100 nM. When IGF-I (0. 1-100 nM; 12 day culture) was combined with
      different doses of DEX, IGF-I still dose dependently stimulated the proliferation
      rate in hOBs regardless of the amount of DEX added. The stimulatory effect of DEX
      (10 nM, 12 days culture) was additive to the effect of 100 nM IGF-I. We conclude
      that AB is an easy and reliable assay for osteoblastic cell proliferation, well
      suited for large scale studies of cell growth using small amounts of cells, and
      that IGF-I partly reverses the glucocorticoid-induced inhibition of osteoblastic
      proliferation.

PMID- 9030478
TI  - Short-term effects of high dose estrogen on tibiae of growing male rats.
AB  - The short-term effects of estrogen at a single high dose (4 mg/kg body weight/day
      for 14 days) were determined on tibiae in the normal (noncastrate) growing male
      rat. In cortical periosteal bone, at a middiaphyseal site devoid of resorbing
      activity, estrogen suppressed periosteal bone formation and apposition rates,
      resulting in a smaller cross-sectional area. In middiaphyseal endocortical bone,
      estrogen had no effect on apposition and formation rates and, because medullary
      area was unchanged, probably had no effect on endocortical bone resorption. In
      the proximal tibial metaphysis, estrogen greatly suppressed longitudinal growth
      rate. In a site within the metaphysis adjusted for the effects of growth,
      cancellous mineral apposition was greatly reduced by the hormone. Estrogen
      treated rats retained more of a fluorochrome label deposited in cancellous bone
      at the beginning of the study than vehicle-treated animals, indicating a reduced
      net bone loss. As a result of the lowered resorption induced by estrogen,
      cancellous bone mass (area and perimeter) were both significantly higher in
      estrogen-treated rats. No evidence was found for an anabolic action of the
      hormone in the male rat; indeed, estrogen reduced indices of bone formation.

PMID- 9030479
TI  - Oral calcium transiently increases calbindin9k gene expression in adult rat
      duodena.
AB  - In rat intestine, the 9 kilodalton calbindin (CaBP9K) is significantly increased
      in vivo by 1,25-dihydroxyvitamin D3 (1, 25(OH)2D3) through a vitamin D (D)
      response element located in the 5'-flanking region of the gene. However, in vitro
      calcium has also been reported to increase CaBP9K gene expression in fetal
      duodenal culture preparations. The aim of the studies was to investigate whether
      calcium feeding alone can influence CaBP9K gene expression in vivo in adult rat
      duodena by evaluating the pattern of expression of its mRNA following short- or
      long-term exposure to oral calcium, comparing the data to exposure to the known
      inducer of the gene, 1, 25(OH)2D3. Hypocalcemic D-depleted rats were acutely or
      chronically supplemented with calcium per os, or with 1,25(OH)2D3 in the presence
      or absence of oral calcium. Short-term calcium feeding was shown to significantly
      increase the expression of the CaBP9K gene to a level similar to that observed in
      1,25(OH)2D3-treated rats but no additive effect between oral calcium and
      1,25(OH)2D3 on the level of its mRNA was observed. Moreover, the calcium effect
      on CaBP9K gene expression was shown to be independent of the circulating ionized
      calcium concentration and, contrary to the effect of 1,25(OH)2D3, not sustained
      following long-term exposure. Our data clearly indicate that oral calcium alone
      has a significant but only transient effect of the expression of the adult rat
      intestinal CaBP9K gene in vivo and that maintenance of its expression requires
      normalization of the D endocrine system.

PMID- 9030480
TI  - Alkaline phosphatase in osteoblasts is down-regulated by pulsatile fluid flow.
AB  - It is our hypothesis that interstitial fluid flow plays a role in the bone
      remodeling response to mechanical loading. The fluid flow-induced expression of
      three proteins (collagen, osteopontin, and alkaline phosphatase) involved in bone
      remodeling was investigated. Rat calvarial osteoblasts subjected to pulsatile
      fluid flow at an average shear stress of 5 dyne/cm2 showed decreased alkaline
      phosphatase (AP) mRNA expression after only 1 hour of flow. After 3 hours of
      flow, AP mRNA levels had decreased to 30% of stationary control levels and
      remained at this level for an additional 5 hours of flow. Steady flow (4 dyne/cm2
      fluid shear stress), in contrast, resulted in a delayed and less dramatic
      decrease in AP mRNA expression to 63% of control levels after 8 hours of flow.
      The reduced AP mRNA expression under pulsatile flow conditions was followed by
      reduced AP enzyme activity after 24 hours. No changes in collagen or osteopontin
      mRNA expression were detected over 8 hours of pulsatile flow. This is the first
      time fluid flow has been shown to affect gene expression in osteoblasts.

PMID- 9030481
TI  - Supraphysiologic levels of testosterone affect cancellous and cortical bone in
      the young female cynomolgus monkey.
AB  - The goal of this study was to evaluate the effects of chronically-elevated male
      levels of the potent androgen testosterone on the quality and quantity of both
      cancellous and cortical bone in a young (mean age 8.0 years), nonhuman female
      primate model (M. fascicularis). Thirteen intact female monkeys received
      continuous testosterone supplementation via subcutaneous implants over a 24-month
      period. A group of 16 untreated, intact, age-matched female monkeys served as
      controls. At sacrifice, the lumbar vertebrae and femora were recovered in order
      to analyze the bone mineral quality and quantity of cancellous and cortical bone,
      respectively, and compared to the control group. Mineralization profiles of the
      vertebrae and femora were obtained using the density fractionation technique.
      Chemical analysis of the three largest fractions retrieved by density
      fractionation was performed to evaluate differences in %Ca, %P, Ca/P ratio, and
      mineral content (%Ca + %PO4) between the control and experimental groups. In
      addition, unfractionated bone powder was examined by X-ray diffraction to
      identify any changes in crystal size. Coronal sections of vertebrae were analyzed
      for structural parameters using histomorphometry and image analysis. Cross
      sections taken at the midshaft diaphyseal femora were analyzed for structural
      macroscopic and intracortical parameters. A nonsignificant shift in the
      mineralization profile of the vertebrae was observed whereas there was a
      significant shift in the mineralization profile towards more dense bone in the
      treated femora as compared with controls (P < 0.05). There was no difference in
      terms of size/strain of the cortical or cancellous bone crystal as detected by X
      ray diffraction. There was a trend towards an increase in cancellous bone area
      (B.Ar.) in the testosterone-treated vertebrae (P = 0.08) as compared with
      controls. The architecture of the cancellous bone remained nonsignificantly
      different between the treatment and control groups as evaluated by image
      analysis. There was a decrease in osteoid perimeter (P = 0.05) in the
      experimental group as compared with controls. There was a significant decrease in
      eroded perimeter measurements in the experimental group as compared with controls
      (P < 0.03). Although there was a trend towards an increase in cancellous bone
      area, mineralization was not significantly different in the vertebrae of
      testosterone-treated female monkeys, indicating that the newly-formed bone tissue
      became relatively normally mineralized over the two-year period. An increase in
      bone area, with indices of an overall decreased remodelling pattern as compared
      with controls, suggests that cancellous bone in the young, nonhuman female
      primate had been receptive to supraphysiologic levels of testosterone
      supplementation over the two-year period. There was a trend for an increase in
      cortical bone area and width with an increased periosteal perimeter in the
      testosterone-treated group as compare with controls. There was an increase in
      intracortical remodelling activity with a significant increase in percent
      porosity (P < 0.05), osteonal bone (P < 0.05), and mean wall width (P < 0.05) in
      the testosterone-treated group. In conclusion, the cancellous bone from female
      monkeys appeared to respond to the antiresorptive stimulus of male levels of
      testosterone with significantly diminished turnover parameters in this
      compartment. In contrast, the cortical bone compartment responded by displaying
      significant intracortical remodelling over a two-year period.

PMID- 9030482
TI  - Inhibitory and stimulatory effects of prostaglandins on osteoclast
      differentiation.
AB  - The effect of prostaglandins (PGs) on osteoclast differentiation, an important
      point of control for bone resorption, is poorly understood. After an initial
      differentiation phase that lasts at least 4 days, murine monocytes, cocultured
      with UMR106 osteoblastic cells (in the presence of 1,25-dihydroxyvitamin D3) give
      rise to tartrate-resistant acid phosphatase (TRAP) positive osteoclast-like cells
      that are capable of lacunar bone resorption. PGE2 strongly inhibits TRAP
      expression and bone resorption in these cocultures. To examine further the
      cellular mechanisms associated with this inhibitory effect, we added PGE2 to
      monocyte/UMR106 cocultures at specific times before, during, and after this
      initial 4-day differentiation period. To determine whether this PGE2 inhibition
      was dependent on the type of stromal cell supporting osteoclast differentiation,
      we also added PGE2 to cocultures of monocytes with ST2 preadipocytic cells.
      Inhibition of bone resorption was greatly reduced when the addition of PGE2 to
      monocyte/UMR106 cocultures was delayed until the fourth day of incubation; when
      delayed until the seventh day, inhibition did not occur. PGE2 inhibition of bone
      resorption was concentration-dependent and at 10(-6) M was also mediated by PGE1
      and PGF2alpha. In contrast to its effects on monocyte/UMR106 cocultures, PGE2
      stimulated bone resorption in monocyte/ST2 cocultures. Both ST2 cells and UMR106
      cells were shown to express functional receptors for PGE2.These results show that
      PGs strongly influence the differentiation of osteoclast precursors and that this
      effect is dependent not only on the type and dose of PG administered, but also on
      the nature of the bone-derived stromal cell supporting this process.

PMID- 9030483
TI  - Structural changes in the large proteoglycan, aggrecan, in different zones of the
      ovine growth plate.
AB  - The large cartilage proteoglycan, aggrecan, was found to vary throughout the
      ovine physis corresponding to the maturational state of the resident
      chondrocytes. Two populations of proteoglycan monomer were observed in articular,
      epiphyseal, and in the resting zone of growth plate cartilage. These
      proteoglycans contained chondroitin sulfate glycosaminoglycan chains sulfated
      predominantly in the 4 position along with lesser amounts of chondroitin-6
      sulfate and keratan sulfate. In the proliferative zone of the growth plate,
      chondrocytes synthesize one population of proteoglycan monomer which was
      significantly larger than monomer populations in articular, epiphyseal, or
      resting zone and this size increase could be attributed to an increase in its
      constituent chondroitin sulfate side chains. As these chondrocytes progress
      through their life cycle they continue to modify the structural characteristics
      of the aggrecan molecule they synthesize. Thus, in the hypertrophic region of the
      growth plate, the proteoglycan monomer is larger again than in the proliferative
      region. Variation in sulfation pattern on aggrecan chondroitin sulfate side
      chains is also observed in the hypertrophic region with an increasing proportion
      of unsulfated residues present, which may play a role in the initiation of
      mineralization. In addition, increasing amounts of the carbohydrate sequence
      recognized by monoclonal antibody 7-D-4 are observed in the hypertrophic zone.

PMID- 9030484
TI  - Voltage-gated calcium channels and nonvoltage-gated calcium uptake pathways in
      the rat incisor odontoblast plasma membrane.
AB  - Odontoblasts participate actively in the transport and accumulation of Ca2+ ions
      to the mineralization front during dentinogenesis. These cells are known to carry
      membrane-bound ATP-driven pumps and Na+/Ca2+ antiports for Ca2+ extrusion, but
      little is known about Ca2+ influx mechanisms into these cells. It has been shown
      that the administration of Ca2+ channel blockers in vivo strongly impairs Ca2+
      uptake in the mineral phase during dentinogenesis in the rat; the present in
      vitro study is aimed at further elucidating odontoblast Ca2+ uptake mechanisms.
      Dissected rat incisor odontoblasts exhibited a pronounced fluorescence when
      incubated with a fluorescently-labeled (STBodipy) dihydropyridine, which is
      specific for voltage-gated Ca2+ channels of the L-type, and this binding was
      competitively abolished by nifedipine. As assayed by fluorescence spectrometry,
      odontoblast Ca2+ uptake was enhanced by the agonistic dihydropyridine BAYK-8644
      (5 micro;M) as well as by plasma membrane depolarization in a high K+ (120 mM)
      medium. The Ca2+ uptake after depolarization was impaired by nifedipine (5
      micro;M). When treated with the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA; 10
      micro;M), a nonvoltage-gated uptake of 45Ca2+ was identified. This uptake was not
      influenced by nifedipine (20 micro;M) but was impaired by lanthanum ions (200
      micro;M). A nonvoltage-gated uptake of Mn2+ into CPA-treated cells could be
      traced using the fura-2 quenching technique. This CPA-induced Ca2+ flux was not
      caused by an alteration of the plasma membrane potential, as assayed with di-8
      ANEPPS. The results demonstrate that Ca2+ flux into dentinogenically active
      odontoblasts occurs through voltage-gated Ca2+ channels of the L-type and by
      nonvoltage-gated, agonist-sensitive Ca2+ uptake pathways.

PMID- 9030485
TI  - Binding of monofluorophosphate to alpha2-macroglobulin and C3.
AB  - After administering an oral dose of monofluorophosphate (MFP) to human beings or
      rats, a fraction of the drug appears in plasma that is bound to proteins,
      establishing a previously undetected compartment of nondiffusible fluoride. This
      article documents experiments performed in vitro, describing the binding of MFP
      to two plasma globulins: alpha2-macroglobulin and C3 (a beta-globulin). MFP binds
      irreversibly to these proteins through a stable bond. MFP binds to purified
      alpha2-macroglobulin or to C3 with a molar ratio MFP: protein close to unity. MFP
      binding reduces significantly the biological activity of these proteins, which
      share in common a macrocyclic 4-residue ring thiolactone (Cys-Gly-Glu-Glu). The
      binding site of MFP is as yet unknown. Protein-bound MFP appeared in the plasma
      of volunteers during the 5-7 hours following intake. Peak concentration of
      protein-bound MFP and maximal reduction of alpha2-macroglobulin activity was
      observed 2 hours after intake. Clearance of protein-bound MFP coincided with the
      return of alpha2-macroglobulin to basal levels.

PMID- 9030486
TI  - Orientation of collagen in osteonal bone.

PMID- 9030487
TI  - Differences in vitamin D status and calcium intake: possible explanations for the
      regional variations in the prevalence of hypercalcemia in tuberculosis.
AB  - The prevalence of hypercalcemia in patients with untreated tuberculosis (TB)
      varies widely between countries. Since the vitamin D status and calcium intake
      are important determinants of hypercalcemia in TB, these two factors were
      compared among four populations (U.K., Hong Kong, Malaysia, Thailand) with a low
      prevalence (<3%) and two populations (Sweden, Australia) with a high prevalence
      (>25%). In the three Asian countries, the circulating vitamin D levels are
      abundant, but the calcium intakes are low. Subjects from the U.K. have the lowest
      circulating vitamin D level of all, although their calcium intake is high. In
      Sweden and Australia, both the circulating vitamin D levels and calcium intakes
      are high. Since serum 1,25(OH)2D concentration will only be raised if its
      substance for extrarenal conversion, 25(OH)D, is plentiful and the effect of a
      given serum 1,25 (OH)2D concentration on serum calcium is determined by the
      calcium intake, it is postulated that the regional variation in the prevalence of
      hypercalcemia in TB may be due to differences in the circulating vitamin D levels
      and calcium intakes in these populations.

PMID- 9030488
TI  - Age-related cortical bone loss at the metacarpal.
AB  - In order to evaluate in vivo the entity of endosteal and periosteal changes with
      age in the two sexes, and their relative contribution to age-related cortical
      bone loss, we undertook a cross-sectional study on a population of normal
      Caucasian subjects. The group included 189 women and 107 men who were studied by
      photodensitometry and radiogrammetry of the second metacarpal bone, derived from
      the same standard hand X-ray. Of the subjects, 134 were 65 years of age or older
      (75 women and 59 men). Metacarpal bone mineral density (BMD) correlated with age
      in both sexes, with an annual bone loss rate of 0.5% in women and 0.15% in men.
      In the over 65 group, correlation was significant only in women, who underwent an
      acceleration in the rate of bone loss (1% per year). Marrow cavity width (M),
      cortical index at the second metacarpal shaft (MI) and external width (W) all
      correlated with age in both sexes, although generally better in the female than
      in the male sex. M almost doubled from the fourth to the ninth decade in women
      and increased 50% in men. In the same age interval, MI showed an annual decrease
      of 0.49% in females and 0.33% in males. In the over 65 group, cortical thinning
      rate was significant in women (0.39% per annum) but not in men (0.14% per annum),
      whereas correlation of W was not significant in either sex. Finally, MI
      correlated with BMD in the whole study population and in the over 65, with a
      female prevalence in correlation strength maintained throughout life. The
      following conclusions can be derived for metacarpal aging: (1) an acceleration in
      cortical bone loss occurs in females after age 65; (2) age-related growth in
      periosteal diameter, although significant in the whole population, is negligible
      in the elderly of both sexes; (3) age-related cortical bone loss is generally
      more dependent on cortical thinning in women than in men.

PMID- 9030489
TI  - Rationale for active vitamin D analog therapy in senile osteoporosis.

PMID- 9030490
TI  - Vitamin D analogs: from renal bone disease to osteoporosis.

PMID- 9030491
TI  - Is there a differential response to alfacalcidol and vitamin D in the treatment
      of osteoporosis?
AB  - : There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin
      D (1,25(OH)2D), and calcium absorption with advancing age, which may lead to
      secondary hyperparathyroidism and bone loss. Studies show a relationship between
      serum 25OHD and bone density in older men and women, with an inverse correlation
      between bone density and parathyroid hormone (PTH). Vitamin D supplementation in
      this age group improves calcium absorption, suppresses PTH, and decreases bone
      loss. Vitamin D many also reduce the incidence of hip and other nonvertebral
      fractures, particularly in the frail elderly who are likely to have vitamin D
      deficiency. Patients with established vertebral osteoporosis have lower calcium
      absorption than age-matched control subjects, possibly due to reduced serum
      1,25(OH)2D or to relative resistance to the action of vitamin D on the bowel.
      Malabsorption of calcium in women with vertebral crush fractures does not usually
      respond to treatment with physiological doses of vitamin D, but can be corrected
      by pharmacological doses of vitamin D or by low doses of calcitriol or
      alfacalcidol. In a recent randomized, controlled study in 46 elderly women with
      radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 micro;g twice
      daily improved calcium absorption, decreased serum PTH, and reduced alkaline
      phosphatase, whereas vitamin D2 500-1000 IU daily had no effect over the 6-month
      study period. Studies of the effect of the vitamin D metabolites in the
      management of elderly women with established vertebral osteoporosis have yielded
      conflicting results, but suggest that alfacalcidol and calcitriol may decrease
      spinal bone loss and reduce the incidence of vertebral fractures. Although
      vitamin D supplementation decreases bone loss and fracture risk in the frail
      elderly, vitamin D metabolites may prove more useful in the treatment of elderly
      women with vertebral osteoporosis.

PMID- 9030492
TI  - Can the fast bone loss in osteoporotic and osteopenic patients be stopped with
      active vitamin D metabolites?
AB  - The aim of this study was to evaluate whether fast trabecular bone loss in
      osteoporotic and osteopenic patients can effectively be treated with active
      vitamin D metabolites. Thirty-one osteoporotic and osteopenic patients were
      monitored between 4 and 22 months before and between 8 and 18 months during the
      treatment. Fast bone losers were designated as osteoporotic or osteopenic
      patients with a loss of trabecular bone density in the radius of 3% or more
      calculated for 1 year. For this differentiation, the high precise peripheral
      quantitative computed tomography system (DENSISCAN 1000) was used
      (reproducibility 0.3% in mixed collectives). The pretreatment loss and the "gain"
      under treatment with active vitamin D metabolites was calculated for 1 year. The
      treatment consisted of either 0.5 micro;g calcitriol daily or 1 micro;g of
      alfacalcidol daily. Before treatment, the trabecular bone loss in the radius/year
      was -6.6 +/- 0.5% (mean +/- SEM). After treatment with vitamin D metabolites, the
      trabecular bone gain in the radius/year was 0.01 +/- 0.6% (mean +/- SEM). The
      difference was highly significant (P < 0.001). In contrast to this, the loss of
      cortical bone density before treatment was -1.8 +/- 0.3% (mean +/- SEM) and the
      reduced loss after treatment -0.2 +/- 0.4% (mean +/- SEM), both values calculated
      for 1 year. This difference was less significant (P < 0. 05). This study shows
      that the treatment with active vitamin D metabolites is very effective in slowing
      fast trabecular bone loss in osteoporotic and osteopenic patients.

PMID- 9030493
TI  - The importance of genetic and nutritional factors in responses to vitamin D and
      its analogs in osteoporotic patients.
AB  - The effects of vitamin D and its analogs on fractures and bone mass have been
      clarified by clinical observations for more than 10 years. Reviewing the results
      of six clinical trials on osteoporotic fractures using activated vitamin D
      analogs, there appeared to be a negative correlation between basal levels of
      calcium intake and the incidence of vertebral fractures in the control groups.
      For example, when daily calcium intake was about 600 mg, there were approximately
      800 vertebral fractures per 1000 persons a year in the controls. When daily
      calcium intake was above 1000 mg, the incidence was less than 400 fractures per
      1000 persons a year. The incidence of fractures decreased by about half in the
      activated vitamin D-treated group compared with the control group, but the most
      marked preventive effects of activated vitamin D on fractures were obtained in
      clinical studies, with daily calcium intakes of 400-800 mg. The effects of
      vitamin D analogs on bone mass were reported in the clinical studies, but the
      results are not consistent. However, these studies suggest that the effects of
      both 1,25(OH)2D3 and 1-alpha(OH)D3 on bone mass were dose dependent, and the
      doses were low in clinical studies in which good results were not obtained.
      Significant effects on bone mass were obtained when more than 0.6 micro;g of
      1,25(OH)2D3, or more than 0.75 micro;g of 1-alpha(OH)D3 was administered, with
      increase in the urinary calcium level being within the acceptable range. Reported
      data indicate that both nonactivated vitamin D and activated vitamin D reduce the
      serum parathyroid hormone level. However, activated vitamin D administration is
      more effective, and is able to reduce bone resorption in postmenopausal,
      osteoporotic patients with a vitamin D-sufficient status. Recent studies
      concerning the polymorphism of the vitamin D-receptor gene emphasize that
      sensitivity to active vitamin D varies between genotypes. In the bb type,
      sensitivity to active vitamin D is high, and calcium absorption efficiency in the
      intestine under low calcium conditions increases with increase in the serum
      1,25(OH)2D level. A significant increase in lumbar bone mineral density was
      obtained after administration of activated vitamin D to osteoporotic patients of
      bb type. However, in the genotype with the B factor, sensitivity to active
      vitamin D was low, and the rate of increase of bone density was low. These data
      suggest that nutritional and genetic factors are critical when using active
      vitamin D and its analogs in the treatment of osteoporosis.

PMID- 9030494
TI  - Active vitamin D metabolites in glucocorticoid-induced osteoporosis.

PMID- 9030495
TI  - Role of alfacalcidiol on bone quality and immunomodulation in autoimmune disease
      and organ transplantation.
AB  - In autoimmune diseases, as well as in organ transplantation, corticosteroids are
      often an obligatory part of the treatment regimen. The deleterious effect of
      corticosteroids on bone metabolism is well known, although still controversial [1
      3]. It is easier to maintain bone mass than to restore it. Although the treatment
      of choice for prevention of bone loss is hormone replacement therapy, it cannot
      always be applied, and for many reasons compliance is low over the world.
      Alternative strategies to prevent bone loss are now tried out in many centers.
      Calcitonin and bisphosphonates are well-known antiresorbing drugs, but costs and
      long-term efficiency for calcitonin and fear for bone toxicity for the
      bisphosphonates limits their use for prevention. An attractive strategy to
      prevent osteoporosis is the treatment with alfacalcidiol because it is a natural
      product with important effects on bone metabolism in physiological and
      pharmacological dosages. Calcium absorption from the gut and mineralization of
      the bone matrix are optimalized by alfacalcidiol. The purpose of this paper is to
      report on our experience with alfacalcidiol concerning bone mass and quality in
      corticosteroid-induced osteoporosis in experimental animals and on long-term bone
      quality in autoimmune diseases and organ transplantation. We have studied the
      effects of alfacalcidiol on bone mass and quality in ovariectomized animals with
      and without corticosteroids. In these fundamental studies we have found that
      alfacalcidiol had a profound protective and curative effect not only on bone mass
      but also on bone quality as tested by mechanical testing, namely, impact
      torsional loading test of whole bones. The combination of alfacalcidiol with
      estrogens was less effective than alfacalcidiol, but more effective than
      estrogens alone [4-6] (Fig. 1).

PMID- 9030496
TI  - The potential use of vitamin D analogs in the treatment of cancer.

PMID- 9030497
TI  - The Gunther temporary inferior vena cava filter for short-term protection against
      pulmonary embolism.
AB  - PURPOSE: To evaluate clinically the Gunther temporary inferior vena cava (IVC)
      filter. METHODS: Eleven IVC filters were placed in 10 patients. Indications for
      filter placement were surgical pulmonary embolectomy in seven patients, pulmonary
      embolism in two patients, and free-floating iliofemoral thrombus in one patient.
      Eight filters were inserted from the right femoral approach, three filters from
      the left. Follow-up was by plain abdominal radiographs, cavography, and duplex
      ultrasound (US). Eight patients received systemic heparinization. Follow-up,
      during 4-60 months after filter removal was by clinical assessment, and imaging
      of the lungs was performed when pulmonary embolism (PE) was suspected. Patients
      received anticoagulation therapy for at least 6 months. RESULTS: Ten filters were
      removed without complications 7-14 days (mean 10 days) after placement. One
      restless patient pulled the filter back into the common femoral vein, and a
      permanent filter was placed. In two patients a permanent filter was placed prior
      to removal. One patient developed sepsis, and one an infection at the insertion
      site. Clinically no recurrent PE developed with the filter in place or during
      removal. One patient had recurrent PE 7 months after filter removal. CONCLUSION:
      The Gunther temporary IVC filter can be safely placed for short-term protection
      against PE. The use of this filter is not appropriate in agitated or
      immunocompromised patients.

PMID- 9030498
TI  - The predictive value of angiographic results for the outcome of percutaneous
      transluminal angioplasty in stenosed femoral bypass grafts.
AB  - PURPOSE: To assess the predictive value of immediate angiographic results after
      percutaneous transluminal angioplasty (PTA) for stenoses in femoral bypass grafts
      using duplex ultrasound (DUS) criteria. METHODS: A 1-year follow-up with DUS was
      performed in 38 patients with 50 stenoses in 41 grafts, treated with PTA for a
      graft stenosis. The indication for PTA according to DUS criteria was a severe
      stenosis in 43 lesions, and a moderate stenosis in 7 lesions. In the moderate
      stenosis group 3 patients showed claudication and 1 patient had a nonhealing
      ulcer. For the purposes of statistical evaluation, primary patency was considered
      present if the graft was not occluded. The graft was considered to have failed
      when it was found to be occluded on DUS, or when secondary interventions
      (surgery, repeat PTA) were performed. RESULTS: After 1 year the cumulative
      primary patency rate was 44% [95% confidence interval (CI) 27.8-59.8]. Stenoses
      with initially good angiographic results after PTA (< 30% residual stenosis) were
      2.9 times more likely to be patent at 1 year than stenoses with initially poor or
      moderate angiographic results (hazard ratio 2.9, 95% CI 1.3-6.4, p = 0.007).
      CONCLUSION: A poor or moderate angiographic result immediately following PTA was
      prognostic for poor long-term results and may indicate a requirement for earlier
      surgical intervention.

PMID- 9030499
TI  - The role of transradial diagnostic angiography.
AB  - PURPOSE: To evaluate the use of 4 Fr radial artery catheters as an alternative to
      both transbrachial and transfemoral approaches. METHODS: Seventy examinations
      were performed via the transradial route using 4 Fr 130-cm-long pigtail
      catheters. Prior to puncture the radial artery was assessed with pulse oximetry
      to ensure that it did not contribute the dominant blood supply to the hand.
      Patients were reassessed for complications within 24 hr of the procedure.
      RESULTS: Acceptable images were obtained in femoral arteriography, arch
      aortography, and selective carotid studies. In three of six renal arteriograms,
      images were suboptimal. There was a total technical failure rate of 5.7%.
      Significant complications were encountered in 4.3%, but no hand ischemia
      occurred. CONCLUSION: The transradial route for arteriography is easy to learn
      and has a low complication rate. It is a reasonable alternative approach to
      transfemoral arteriography for true outpatient peripheral angiography and in
      cases where the transfemoral route is not feasible, though it did not prove
      satisfactory for renal arteriography in hypertensive patients.

PMID- 9030500
TI  - Treatment of symptomatic pelvic varices by ovarian vein embolization.
AB  - PURPOSE: Pelvic congestion syndrome is a common cause of chronic pelvic pain in
      women and its association with venous congestion has been described in the
      literature. We evaluated the potential benefits of lumbo-ovarian vein
      embolization in the treatment of lower abdominal pain in patients presenting with
      pelvic varicosities. METHODS: Nineteen patients were treated. There were 13
      unilateral embolizations, 6 initial bilateral treatments and 5 treated
      recurrences (a total of 30 procedures). All embolizations were performed with
      either enbucrilate and/or macrocoils, and there was an average clinical and
      Doppler duplex follow-up of 15.4 months. RESULTS: The initial technical success
      rate was 96.7%. There were no immediate or long-term complications. Variable
      symptomatic relief was observed in 73.7% of cases with complete responses in
      57.9%. All 8 patients who had partial or no pain relief complained of
      dyspareunia. The direct relationship between varices and chronic pelvic pain was
      difficult to ascertain in a significant number of clinical failures. CONCLUSION:
      Transcatheter embolization of lumbo-ovarian varices is a safe technique offering
      symptomatic relief of pelvic pain in the majority of cases. The presence of
      dyspareunia seemed to be a poor prognostic factor, indicating that other causes
      of pelvic pain may coexist with pelvic varicosities.

PMID- 9030501
TI  - Interventional therapeutic techniques in Budd-Chiari syndrome.
AB  - PURPOSE: To analyze the results obtained with percutaneous therapeutic procedures
      in patients with Budd-Chiari syndrome (BCHS). METHODS: Between August 1991 and
      April 1993, seven patients with BCHS were treated in our hospital. Three
      presented with a congenital web; in another three cases the hepatic veins and/or
      the inferior vena cava (IVC) were compromised after major hepatic surgery; one
      patient presented with a severe stenosis of the intrahepatic IVC due to
      hepatomegaly. RESULTS: One of the patients with congenital web has required
      several new dilatations due to restenosis; one patient required a transjugular
      intrahepatic portosystemic shunt procedure while awaiting a liver
      transplantation. The two postsurgical patients with stenosed hepatic veins did
      not require any new procedure after the placement of metallic endoprostheses.
      However, the patient with liver transplantation presented IVC restenosis after
      balloon angioplasty that required the deployment of metallic endoprostheses. In
      the patient with hepatomegaly a self-expandable prosthesis was placed in the
      intrahepatic portion of the IVC before (4 months) a liver transplantation.
      CONCLUSION: Interventional therapeutic techniques offer a wide variety of
      possibilities for the treatment of patients with BCHS. For IVC stenoses, the
      results obtained with balloon angioplasty are at least as good as those obtained
      with surgery.

PMID- 9030502
TI  - Embolization of portal-systemic shunts in cirrhotic patients with chronic
      recurrent hepatic encephalopathy.
AB  - PURPOSE: To evaluate the efficacy of embolization of portal-systemic shunts in
      cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). METHODS:
      Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4
      women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1
      had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein
      shunt. Shunt embolization was performed using stainless steel coils, with a
      percutaneous transhepatic portal vein approach in 4 patients and a transrenal
      vein approach in 3 patients. RESULTS: After embolization, the shunt disappeared
      in 4 patients on either ultrasound pulsed Doppler monitoring or portography.
      Complications observed in the 7 patients were fever, transient pleural effusion,
      ascites, and mild esophageal varices. For 3-6 months after embolization, the 4
      patients whose shunts disappeared showed minimal or no reappearance of a shunt,
      and had no recurrence of encephalopathy. The serum ammonia levels decreased and
      electroencephalograms also improved. One of the 4 patients, who developed mild
      esophageal varices, required no treatment. Treatment was effective in 3 of the 4
      patients (75%) who underwent embolization via a transhepatic portal vein.
      CONCLUSION: Transvascular embolization of shunts improved the outcome in 4 of 7
      patients. The most effective embolization was achieved via the percutaneous
      transhepatic portal vein approach.

PMID- 9030503
TI  - Partial splenic embolization for hypersplenism concomitant with or after arterial
      embolization of hepatocellular carcinoma in 30 patients.
AB  - PURPOSE: To study the value of partial splenic embolization (PSE) for the
      treatment of hypersplenism in patients undergoing embolization of hepatocellular
      carcinoma (HCC). METHODS: Transcatheter hepatic arterial embolization (THAE)
      combined with PSE was performed in 30 patients with HCC complicating liver
      cirrhosis, portal hypertension, and hypersplenism. Gelfoam sponge was used as the
      embolic material for PSE and limited to 100-150 pieces. RESULTS: More than 50% of
      splenic parenchyma was infarcted in 27 patients. Leukopenia and thrombocytopenia
      were corrected by PSE in 25 of 27 patients with hypersplenism. In 26 patients
      with esophageal varices, including 5 patients with bleeding, no rebleeding
      occurred during a 6-17 month follow-up. Hypersplenism was not corrected in 2 of 3
      patients whose infarcted splenic parenchyma was less than 50%. No splenic
      abscesses or other severe complications were observed. Of the 30 patients
      treated, 19 are still alive after 1 year. CONCLUSIONS: THAE combined with PSE is
      a safe and effective measure for patients with HCC.

PMID- 9030505
TI  - Percutaneous transhepatic intraductal biliary sonography for lymph node staging
      at 12.5 MHz in malignant bile duct obstruction: work in progress.
AB  - PURPOSE: To assess the value of intraductal ultrasound (US) for lymph node
      staging in malignant biliary obstruction. METHODS: Eighteen patients with
      malignant extrahepatic obstruction were imaged during percutaneous bile duct
      drainage with a mechanically rotating US transducer at 12.5 MHz. Detectable lymph
      nodes were classified as malignant when two of three criteria (hypoechoic,
      rounded, conspicuous margins) were fulfilled. The results were compared with
      histopathological data in 8 patients and follow-up CT findings in 10 patients.
      RESULTS: In 15 of 18 patients (83%) malignant lymph node involvement was
      suspected at intraductal US and in 5 of 18 patients (28%) during CT.
      Histopathological investigation after operation (n = 8) and follow-up CT studies
      (n = 10) revealed the presence of malignant nodal involvement in 13 of 18 (72%)
      patients. The sensitivity, specificity, and accuracy of transhepatic intraductal
      biliary US in determining merely the presence or absence of malignant lymph nodes
      without specific topographic assignment were 92%, 40%, and 78%, respectively.
      CONCLUSION: These preliminary results suggest that intraductal US may develop
      into a promising adjunctive modality during percutaneous bile duct drainage in
      patients with suspected malignant regional lymph node involvement.

PMID- 9030504
TI  - Minimally invasive catheter implantation for regional chemotherapy of the liver:
      a new percutaneous transsubclavian approach.
AB  - PURPOSE: Development of a percutaneously implantable catheter system for regional
      chemotherapy of liver metastases and its application in patients with surgically
      implanted but dislocated catheters. METHODS: Thirty-three patients with liver
      metastases of colorectal tumors were submitted to percutaneous puncture of the
      subclavian artery and insertion of a catheter whose tip was placed in the proper
      hepatic artery and whose end was subcutaneously connected with an infusion pump.
      RESULTS: The mean duration of therapy via the percutaneously inserted catheter
      was 27 weeks (+/-14 weeks). The most frequent complication was disconnection of
      the therapy catheter from the tube of the infusion pump. Eighty percent of all
      complications were corrected by reintervention. The therapy drop-out rate due to
      catheter-associated complications was 9%. CONCLUSION: Percutaneous insertion of a
      catheter for regional chemotherapy of the liver is a relatively uncomplicated
      method with high patient acceptance and simple access for reintervention.

PMID- 9030506
TI  - Suprarenal inferior vena cava filter placement prior to transcatheter arterial
      embolization (TAE) of a renal cell carcinoma with large renal vein tumor
      thrombus: prevention of pulmonary tumor emboli after TAE.
AB  - To prevent embolization of necrotic renal vein tumor after transcatheter
      embolization of a left renal cell carcinoma, we placed a suprarenal Bird's nest
      inferior vena cava filter. The patient tolerated the procedure well and had
      extensive tumor infarction including the tumor thrombus on 6-month follow-up
      computed tomography.

PMID- 9030507
TI  - Right atrial thrombi: percutaneous mechanical thrombectomy.
AB  - The current therapeutic options for right atrial thrombi-surgical embolectomy and
      thrombolysis-are associated with high mortality and such patients often have
      contraindications to these therapeutic options. The purpose of this study was to
      evaluate the feasibility of endovascular right atrial embolectomy. Two patients
      with contraindications to thrombolysis and surgery were treated by a femoral
      approach. A catheter was placed in the right atrium, under fluoroscopic control,
      and a basket device was used to trap the thrombus. The location and extent of the
      thrombus was established before the procedure by transesophageal echocardiography
      (TEE) and the procedure was performed with TEE and fluoroscopy. Thrombi were
      withdrawn in the basket into the inferior vena cava (IVC) and a filter was
      inserted by a jugular approach and positioned in the IVC, just above the thrombi.
      The basket was removed leaving the thrombus below the filter. One patient died
      immediately after the procedure. In conclusion, endovascular extraction of right
      atrial thrombi may represent a potential therapeutic alternative, particularly in
      patients with contraindications to thrombolysis and surgery.

PMID- 9030508
TI  - Percutaneous fenestration of aortic dissection: salvage of an ischemic solitary
      left kidney.
AB  - The false channel of a type III aortic dissection caused acute renal ischemia by
      compression of the origin of the left renal artery in a patient with status post
      right nephrectomy. To relieve the ischemia and restore renal function,
      percutaneous balloon fenestration was performed successfully.

PMID- 9030509
TI  - Embolization of nonvariceal portosystemic collaterals in transjugular
      intrahepatic portosystemic shunts.
AB  - Percutaneous embolization of large portosystemic collaterals was performed in
      three patients following placement of a transjugular intrahepatic portosystemic
      shunt in order to improve hepatopetal portal flow. Improved hepatic portal
      perfusion was achieved in these cases, thereby theoretically reducing the risk of
      chronic hepatic encephalopathy.

PMID- 9030510
TI  - Dialysis grafts arterial plug: retrieval using the tulip sheath device in vitro.
AB  - The "arterial plug" is a resistant thrombus that frequently persists at the
      arterial anastomosis of clotted hemodialysis grafts following thrombolytic
      therapy. We studied the physical and morphological characteristics of the plug
      and determined the feasibility of transcatheter removal in vitro using the tulip
      compression thrombectomy system. Sixteen thrombus plugs were recovered during
      surgical thrombectomy of clotted human dialysis grafts. The physical and gross
      physical characteristics of all plugs were analyzed. Eight specimens were
      evaluated microscopically. Transcatheter compression thrombectomy of eight plugs
      was attempted in vitro. Each plug was embedded in a polyvinyl tube filled with
      newly clotted blood and connected to a flow circuit. First, balloon-assisted
      aspiration thrombectomy (BAT) of soft thrombus was performed, while sparing the
      distal-most segment containing the plug. The tulip sheath was then introduced
      facing the "arterial end" of the tube. The thrombus segment containing the plug
      was pulled back into the tulip mesh using either a 3 Fr Fogarty balloon catheter
      or a self-expanding rake. The tulip was closed to compress and remove the trapped
      plug. Near-complete thrombectomy of soft clot was achieved in all tested tubes.
      Compression and retrieval of the entire arterial plug was successful in all
      except one, where only partial compression of the plug occurred, presumably due
      to fibrotic changes. No fragmentation or embolization occurred in the remaining
      procedures. Spongy consistency was noted in 94% of the specimens. Microscopic
      evaluation showed organized layered thrombus with compaction in five plugs.
      Transcatheter removal of a thrombus plug is feasible in vitro using the tulip
      compression-thrombectomy system.

PMID- 9030511
TI  - A simple trick to facilitate bleeding control after percutaneous hemodialysis
      fistula and graft interventions.
AB  - A simple technique of performing a circular subcutaneous suture that helps to
      stop bleeding after cannulation of hemodialysis grafts and fistulas following
      percutaneous revision is described.

PMID- 9030512
TI  - Re: chronic superior vena cava occlusion related to fibrosing mediastinitis
      treated with self-expanding shunts.

PMID- 9030513
TI  - Re: in situ formation of a loop snare for retrieval of a foreign body without a
      free end.

PMID- 9030514
TI  - Identification of a novel calcium-binding protein that interacts with the
      integrin alphaIIb cytoplasmic domain.
AB  - The mechanism by which platelets regulate the function of integrin alphaIIbbeta3
      (or GPIIb/IIIa), the platelet fibrinogen receptor, is unknown but may involve the
      binding of proteins or other factors to integrin cytoplasmic domains. To identify
      candidate cytoplasmic domain binding proteins, we screened a human fetal liver
      cDNA library in the yeast two-hybrid system, using the alphaIIb cytoplasmic
      domain as "bait," and isolated a novel 855-base pair clone. The open reading
      frame encodes a novel 191-amino acid polypeptide (termed CIB for calcium- and
      integrin-binding protein) that appears to be specific for the cytoplasmic domain
      of alphaIIb, since it does not interact with the alphav, alpha2, alpha5, beta1,
      or beta3 integrin cytoplasmic domains in the yeast two-hybrid system. This
      protein has sequence homology to two known Ca2+-binding regulatory proteins,
      calcineurin B (58% similarity) and calmodulin (56% similarity), and has two EF
      hand motifs corresponding to the two C-terminal Ca2+ binding domains of these
      proteins. Moreover, recombinant CIB specifically binds 45Ca2+ in blot overlay
      assays. Using reverse transcriptase-polymerase chain reaction and Western blot
      analysis, we detected CIB mRNA and protein ( approximately 25 kDa), respectively,
      in human platelets. An enzyme-linked immunosorbent assay performed using either
      immobilized recombinant CIB or monoclonal antibody-captured alphaIIbbeta3
      indicates a specific interaction between CIB and intact alphaIIbbeta3. These
      results suggest that CIB is a candidate regulatory molecule for integrin
      alphaIIbbeta3.

PMID- 9030515
TI  - Isolation and characterization of a GTPase activating protein specific for the
      Rab3 subfamily of small G proteins.
AB  - The Rab small G protein family, consisting of nearly 30 members, is implicated in
      intracellular vesicle trafficking. They cycle between the GDP-bound and GTP-bound
      forms, and the latter is converted to the former by the action of a GTPase
      activating protein (GAP). No GAP specific for each Rab family member or Rab
      subfamily has been isolated in mammal. Here we purified a GAP with Rab3A as a
      substrate from rat brain. The purified protein was specifically active on the
      Rab3 subfamily members (Rab3A, -B, -C, and -D). Of this subfamily, Rab3A and -C
      are implicated in Ca2+-dependent exocytosis, particularly in neurotransmitter
      release. This GAP, named Rab3 GAP, was active on the lipid-modified form, but not
      on the lipid-unmodified form. Rab3 GAP showed a minimum molecular mass of about
      130 kDa on SDS-polyacrylamide gel electrophoresis. We cloned its cDNA from a
      human brain cDNA library, and the isolated cDNA encoded a protein with a Mr of
      110,521 and 981 amino acids, which showed no homology to any known protein. The
      recombinant protein exhibited GAP activity toward the Rab3 subfamily members, and
      the catalytic domain was located at the C-terminal region. Northern blot analysis
      indicated that Rab3 GAP was ubiquitously expressed.

PMID- 9030516
TI  - Proteasome- and p53-dependent masking of signal transducer and activator of
      transcription (STAT) factors.
AB  - Hepatoma Hep3B cell lines stably expressing a temperature-sensitive p53 species
      (p53-Val-135) displayed a reduced response to interleukin-6 (IL-6) when cultured
      at the wild-type (wt) p53 temperature (Wang, L., Rayanade, R., Garcia, D., Patel,
      K., Pan, H., and Sehgal, P. B. (1995) J. Biol. Chem. 270, 23159-23165). We now
      report that in such cultures IL-6 caused a rapid (20-30 min) and marked loss of
      cellular immunostaining for STAT3 and STAT5, but not for STAT1. The loss of STAT3
      and STAT5 immunostaining was transient (lasted 120 min) and tyrosine kinase
      dependent, and even though the loss was blocked by the proteasome inhibitors
      MG132 and lactacystin it was not accompanied by changes in cellular levels of
      STAT3 and STAT5 proteins suggesting that IL-6 triggered a rapid masking but not
      degradation of these transcription factors. STAT3 and STAT5 masking was
      accompanied by a reduction in IL-6-induced nuclear DNA-binding activity. The data
      suggest that p53 may influence Jak-STAT signaling through a novel indirect
      mechanism involving a wt p53-dependent gene product which upon cytokine addition
      is activated into a "STAT-masking factor" in a proteasome-dependent step.

PMID- 9030517
TI  - Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene
      expression by IGF-I and basic fibroblastic growth factor.
AB  - Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by
      various stimuli, including hormones, growth factors, and nutritional status. We
      have investigated the molecular mechanism by which two growth factors, insulin
      like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate
      IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF
      IR promoter activity. This effect is mediated by a region of the IGF-IR promoter
      located between nucleotides -476 and -188 in the 5'-flanking region. In contrast,
      IGF-I decreases the IGF-IR mRNA levels. IGF-I down-regulates IGF-IR
      transcriptional activity as deduced from experiments in which the levels of pre
      mRNA and mRNA were measured. IGF-I reduced pre-mRNA and mRNA levels in parallel,
      while the mRNA stability was found to be unchanged by IGF-I treatment. While
      these results strongly suggest an effect of IGF-I on IGF-IR transcriptional
      activity, no specific IGF-I response element was demonstrated in the 5'
      untranslated region or 5'-flanking region studied. Thus, bFGF and IGF-I have
      differential effects on IGF-IR gene transcription, with the IGF-I response region
      as yet unidentified.

PMID- 9030518
TI  - Residues of the Rho family GTPases Rho and Cdc42 that specify sensitivity to Dbl
      like guanine nucleotide exchange factors.
AB  - The Dbl-like guanine nucleotide exchange factor (GEF) Lbc oncoprotein
      specifically activates the small GTP-binding protein Rho in mammalian fibroblasts
      to induce transformation and actin stress fiber formation, whereas another Dbl
      related molecule, Cdc24, stimulates guanine nucleotide exchange of the Rho family
      GTPase Cdc42 to elicit effects on both gene induction and actin-based
      cytoskeleton change in Saccharomyces cerevisiae. To understand the mechanism of
      these functional interactions, we have taken a biochemical approach to probe the
      sites on Rho and Cdc42 that are involved in coupling to their respective GEFs,
      the Lbc and Cdc24 proteins. Point mutations in the switch II region of the small
      G-proteins, many of which would affect the interaction with GEF in the case of
      Ras, or a mutation in the switch I region that was identified as a contact site
      between Rab3A and Rab GEF had little effect on RhoA or Cdc42Hs with regard to the
      ability to interact with Lbc or Cdc24, suggesting that there exists a unique
      mechanism of regulation of the Rho family proteins by their GEFs. Analysis of a
      panel of chimeras made between RhoA and Cdc42Hs, which all maintained the ability
      to respond to Dbl, their mutual GEF, and to GTPase-activating protein, revealed
      that at least two distinct sites in each of the GTPases are required for
      activation by the respective GEFs. Further site-directed mutagenesis studies
      showed that the conserved residue Tyr32 in the putative effector region of both
      GTPases (numbered by Cdc42Hs) is critical for binding of the GEFs and that
      specific recognition for Lbc or Cdc24 is achieved at least in part through
      residues Lys27 of Rho and Gln116 of Cdc42. Moreover, the loss of GEF
      responsiveness of a RhoA mutation (D76Q) was found to be caused by the impaired
      GEF catalysis, not by a change in the GEF binding affinity. Together, these
      results indicate that multiple sites of the Rho GTPases are involved in the
      regulation by GEFs, contributing to GEF binding or GEF catalysis, and raise the
      possibility that activation of each Rho family G-protein by a specific GEF may
      engage in a distinct mechanism.

PMID- 9030519
TI  - Energy metabolism during apoptosis. Bcl-2 promotes survival in hematopoietic
      cells induced to apoptose by growth factor withdrawal by stabilizing a form of
      metabolic arrest.
AB  - We have investigated cell metabolism during apoptosis in the murine interleukin-3
      (IL-3)-dependent cell line Bo and two derivative clones (B14 and B15)
      overexpressing human bcl-2a. On removal of IL-3, Bo cells underwent apoptosis
      within 8 h, whereas B14 and B15 cells were resistant for at least 24 h.
      Metabolically, Bo, B14, and B15 cells were indistinguishable from each other. All
      were insensitive to mitochondrial poisons, derived ATP entirely by glycolysis,
      and maintained similar mitochondrial membrane potentials measured by rhodamine
      123 fluorescence with or without IL-3. All virtually ceased glycolysis and
      production of lactic acid on IL-3 withdrawal but maintained intracellular [ATP]
      until in Bo cultures the cells began to apoptose. B14 and B15 cells became
      glycolytically arrested but maintained stable ATP levels during protection from
      apoptosis. Depletion of intracellular ATP by uncoupling the mitochondrial ATPase
      with 2,4-dinitrophenol or carbonyl cyanide p-trifluoromethoxyphenylhydrazone
      induced apoptosis in Bo cells with or without IL-3, but not in B14 or B15 cells.
      bcl-2-overexpressing cells were recoverable with high plating efficiency even
      after prolonged exposure to 2,4-dinitrophenol. We conclude that IL-3 withdrawal
      leads to arrest of energy metabolism in which ATP levels are maintained. In Bo
      cells this is followed by apoptosis, whereas in bcl-2-overexpressing cells this
      state is stably prolonged. ATP depletion is a strong apoptotic signal which
      overrides IL-3 signaling in normal cells but is ineffective in bcl-2
      overexpressing cells. Prolonged metabolic arrest and resistance to ATP depletion
      facilitated by bcl-2 are both reversible. Persistent reversible metabolic
      dormancy would provide cells with a survival advantage in nonsustainable
      environments (e.g. hypoxia or substrate lack) and suggests a mechanism for the
      survival advantage displayed by cells overexpressing bcl-2.

PMID- 9030520
TI  - A novel post-translational modification involving bromination of tryptophan.
      Identification of the residue, L-6-bromotryptophan, in peptides from Conus
      imperialis and Conus radiatus venom.
AB  - We report a novel post-translational modification involving halogenation of
      tryptophan in peptides recovered from the venom of carnivorous marine cone snails
      (Conus). The residue, L-6-bromotryptophan, was identified in the sequence of a
      heptapeptide, isolated from Conus imperialis, a worm-hunting cone. This peptide
      does not elicit gross behavioral symptoms when injected centrally or peripherally
      in mice. L-6-Bromotryptophan was also identified in a 33-amino acid peptide from
      Conus radiatus; this peptide has been shown to induce a sleep-like state in mice
      of all ages and is referred to as bromosleeper peptide. The sequences of the two
      peptides and were determined using a combination of mass spectrometry, amino
      acid, and chemical sequence analyses, where Pca = pyroglutamic acid, Hyp =
      hydroxyproline, Gla = gamma-carboxyglutamate, and Trp* = L-6-bromotryptophan. The
      precise structure and stereochemistry of the modified residue were determined as
      L-6-bromotryptophan by synthesis, co-elution, and enzymatic hydrolysis
      experiments. To our knowledge this is the first documentation of tryptophan
      residues in peptides/proteins being modified in a eukaryotic system and the first
      report of halogenation of tryptophan in vivo.

PMID- 9030521
TI  - A point mutation in the mitochondrial cytochrome b gene obviates the requirement
      for the nuclear encoded core protein 2 subunit in the cytochrome bc1 complex in
      Saccharomyces cerevisiae.
AB  - A yeast mutant (cor2-45) in which approximately half of the C terminus of core
      protein 2 of the cytochrome bc1 complex is lacking due to a frameshift mutation
      that introduces a stop at codon 197 in the COR2 gene fails to assemble the
      cytochrome bc1 complex and does not grow on non-fermentable carbon sources that
      require respiration. The loss of respiration is more severe with this frameshift
      mutation than with the complete deletion of the COR2 gene, suggesting deleterious
      effects of the truncated core 2 protein. A search for extragenic suppressors of
      the nuclear cor2-45 mutation resulted (in addition to the expected nuclear
      suppressors) in the isolation of a suppressor mutation in the mitochondrial DNA
      that replaces serine 223 by proline in cytochrome b. Assembly of the cytochrome
      bc1 complex and the respiratory deficient phenotype of the cor2-45 mutant are
      restored by the proline for serine replacement in cytochrome b. Surprisingly,
      this amino acid replacement in cytochrome b corrects not only the phenotype
      resulting from the cor2-45 frameshift mutation, but it also obviates the need for
      core protein 2 in the cytochrome bc1 complex since it alleviates the respiratory
      deficiency resulting from the complete deletion of the COR2 gene. This is the
      first report of a homoplasmic missense point mutation of the mitochondrial DNA
      acting as a functional suppressor of a mutation located in a nuclear gene and the
      first demonstration that the supernumerary core protein 2 subunit is not
      essential for the electron transfer and energy transducing functions of the
      mitochondrial cytochrome bc1 complex.

PMID- 9030522
TI  - The rabbit kidney tubule simultaneously degrades and synthesizes glutamate. A 13C
      NMR study.
AB  - The rabbit kidney does not readily metabolize but synthesizes glutamine at high
      rates by pathways that remain poorly defined. Therefore, the metabolism of
      variously labeled [13C]- and [14C]glutamates has been studied in isolated rabbit
      kidney tubules with and without acetate. CO2, glutamine, and alanine were the
      main carbon and nitrogenous end products of glutamate metabolism but no ammonia
      accumulated. Absolute fluxes through enzymes involved in glutamate metabolism,
      including enzymes of four different cycles operating simultaneously, were
      assessed by combining mainly the 13C NMR data with a new model of glutamate
      metabolism. In contrast to a previous conclusion of Klahr et al. (Klahr, S.,
      Schoolwerth, A. C., and Bourgoignie, J. J. (1972) Am. J. Physiol. 222, 813-820),
      glutamate metabolism was found to be initiated by glutamate dehydrogenase at high
      rates. Glutamate dehydrogenase also operated at high rates in the reverse
      direction; this, together with the operation of the glutamine synthetase
      reaction, masked the release of ammonia. Addition of acetate stimulated the
      operation of the "glutamate --> alpha-ketoglutarate --> glutamate" cycle and the
      accumulation of glucose but reduced both the net oxidative deamination of
      glutamate and glutamine synthesis. Acetate considerably increased flux through
      alpha-ketoglutarate dehydrogenase and citrate synthase at the expense of flux
      through phosphoenolpyruvate carboxykinase; acetate also caused a large decrease
      in flux through alanine aminotransferase, pyruvate dehydrogenase, and the
      "substrate cycle" involving oxaloacetate, phosphoenolpyruvate, and pyruvate.

PMID- 9030523
TI  - Model applicable to NMR studies for calculating flux rates in five cycles
      involved in glutamate metabolism.
AB  - Based on the same principles as those utilized in a recent study for modeling
      glucose metabolism (Martin, G., Chauvin, M. F., Dugelay, S., and Baverel, G.
      (1994) J. Biol. Chem. 269, 26034-26039), a method is presented for determining
      metabolic fluxes involved in glutamate metabolism in mammalian cells. This model
      consists of five different cycles that operate simultaneously. It includes not
      only the tricarboxylic acid cycle, the "oxaloacetate --> phosphoenolpyruvate -->
      pyruvate --> oxaloacetate" cycle and the "oxaloacetate --> phosphoenolpyruvate -
      > pyruvate --> acetyl-CoA --> citrate --> oxaloacetate" cycle but also the
      "glutamate --> alpha-ketoglutarate --> glutamate" and the "glutamate -->
      glutamine --> glutamate" cycles. The fates of each carbon of glutamate, expressed
      as ratios of integrated transfer of this carbon to corresponding carbons in
      subsequent metabolites, are described by a set of equations. Since the data
      introduced in the model are micrograms of atom of traced carbon incorporated into
      each carbon of end products, the calculation strategy was determined on the basis
      of the most reliable parameters determined experimentally. This model, whose
      calculation routes offer a large degree of flexibility, is applicable to data
      obtained by 13C NMR spectroscopy, gas chromatography - mass spectrometry, or 14C
      counting in a great variety of mammalian cells.

PMID- 9030524
TI  - 5-Formyltetrahydrofolate regulates homocysteine remethylation in human
      neuroblastoma.
AB  - The metabolic role of 5-formyltetrahydrofolate is not known; however, it is an
      inhibitor of several folate-dependent enzymes including serine
      hydroxymethyltransferase. Methenyltetrahydrofolate synthetase (MTHFS) is the only
      enzyme known to metabolize 5-formyltetrahydrofolate and catalyzes the conversion
      of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate. In order to address
      the function of 5-formyltetrahydrofolate in mammalian cells, intracellular 5
      formyltetrahydrofolate levels were depleted in human 5Y neuroblastoma by
      overexpressing the human cDNA encoding MTHFS (5YMTHFS cells). When cultured with
      2 mM exogenous glycine, the intracellular serine and glycine concentrations in
      5YMTHFS cells are elevated approximately 3-fold relative to 5Y cells; 5YMTHFS
      cells do not contain measurable levels of free methionine and display a 30-40%
      decrease in cell proliferation rates compared with 5Y cells. Medium supplemented
      with pharmacological levels of exogenous folinate or methionine ameliorated the
      glycine induced growth inhibition. Analysis of the folate derivatives
      demonstrated that 5-methyltetrahydrofolate accounts for 30% of total cellular
      folate in 5Y cells when cultured with 5 mM exogenous glycine. 5YMTHFS cells do
      not contain detectable levels of 5-methyltetrahydrofolate under the same culture
      conditions. These results suggest that 5-formyltetrahydrofolate inhibits serine
      hydroxymethyltransferase activity in vivo and that serine synthesis and
      homocysteine remethylation compete for one-carbon units in the cytoplasm.

PMID- 9030525
TI  - Integration of tetracycline regulation into a cell-specific transcriptional
      enhancer.
AB  - The pancreas-specific transcriptional enhancer of the rat elastase I gene was
      modified by substituting, in turn, each of its three individual constitutive
      elements with the tetO element, which confers regulation by exogenous
      tetracycline in the presence of the hybrid tetO binding transactivator (tTA).
      Whereas the unmodified enhancer was active in transfected acinar tumor cells,
      substitution of individual elements with the tet-responsive element abolished
      activity. The modified enhancers were reactivated in the presence of the tTA and,
      upon addition of tetracycline, were silenced. Thus, substitution of individual
      enhancer elements renders the enhancer responsive to regulation by tetracycline.
      Moreover, the tTA-activated levels were 2-8-fold greater than the unmodified
      enhancer. The acinar cell specificity of the unmodified enhancer was retained;
      none of the tetO-substituted enhancers were activated by tTA in a variety of
      nonacinar cell lines. These results show that a foreign and artificial
      transcriptional activator, tTA, can be incorporated into an enhancer to create a
      novel, efficient, and regulatable transcriptional control region whose cell
      specificity is retained.

PMID- 9030526
TI  - Interaction of PKN with alpha-actinin.
AB  - PKN is a fatty acid- and Rho-activated serine/threonine protein kinase, having a
      catalytic domain homologous to protein kinase C family. To identify components of
      the PKN-signaling pathway such as substrates and regulatory proteins of PKN, the
      yeast two-hybrid strategy was employed. Using the N-terminal region of PKN as a
      bait, cDNAs encoding actin cross-linking protein alpha-actinin, which lacked the
      N-terminal actin-binding domain, were isolated from human brain cDNA library. The
      responsible region for interaction between PKN and alpha-actinin was determined
      by in vitro binding analysis using the various truncated mutants of these
      proteins. The N-terminal region of PKN outside the RhoA-binding domain was
      sufficiently shown to associate with alpha-actinin. PKN bound to the third
      spectrin-like repeats of both skeletal and non-skeletal muscle type alpha
      actinin. PKN also bound to the region containing EF-hand-like motifs of non
      skeletal muscle type alpha-actinin in a Ca2+-sensitive manner and bound to that
      of skeletal muscle type alpha-actinin in a Ca2+-insensitive manner. alpha-Actinin
      was co-immunoprecipitated with PKN from the lysate of COS7 cells transfected with
      both expression constructs for PKN and alpha-actinin lacking the actin-binding
      domain. In vitro translated full-length alpha-actinin containing the actin
      binding site hardly bound to PKN, but the addition of phosphatidylinositol 4, 5
      bisphosphate, which is implicated in actin reorganization, stimulated the binding
      activity of the full-length alpha-actinin with PKN. We therefore propose that PKN
      is linked to the cytoskeletal network via a direct association between PKN and
      alpha-actinin.

PMID- 9030527
TI  - Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility.
AB  - Cyclic AMP-dependent protein kinase (PKA) is anchored at specific subcellular
      sites through the interaction of the regulatory subunit (R) with protein kinase A
      anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic
      peptides containing this amphipathic helix domain competitively disrupt PKA
      binding to AKAPs and cause a loss of PKA modulation of cellular responses. In
      this report we use S-Ht31, a cell-permeant anchoring inhibitor peptide, to study
      the role of PKA anchoring in sperm. Our analysis of three species of mammalian
      sperm detected three isoforms of PKA (RIIalpha, RIIbeta, and RIbeta) and one 110
      kDa AKAP. The addition of S-Ht31 to bovine caudal epididymal sperm inhibits
      motility in a time- and concentration-dependent manner. A control peptide, S-Ht31
      P, identical to S-Ht31 except for a proline for isoleucine substitution to
      prevent amphipathic helix formation, had no effect on motility. The inhibition of
      motility by S-Ht31 is reversible but only if calcium is present in the suspension
      buffer, suggesting a role for PKA anchoring in regulating cellular calcium
      homeostasis. Surprisingly, inhibition of PKA catalytic activity had little effect
      on basal motility or motility stimulated by agents previously thought to work via
      PKA activation. These data suggest that the interaction of the regulatory subunit
      of PKA with sperm AKAPs, independent of PKA catalytic activity, is a key
      regulator of sperm motility and that disruption of this interaction using cell
      permeable anchoring inhibitor peptides may form the basis of a sperm-targeted
      contraceptive.

PMID- 9030528
TI  - Fcgamma receptor I activation triggers a novel Ca2+-activated current selective
      for monovalent cations in the human monocytic cell line, U937.
AB  - Previous reports have suggested that receptors for immunoglobulin G (IgG),
      FcgammaRs, directly activate a nonselective cation channel (Young, J. D.-E.,
      Unkeless, J. C., Young, T. M., Mauro, A., and Cohn, Z. A. (1983) Nature 306, 186
      189; Nelson, D. J., Jacobs, E. R., Tang, J. M., Zeller, J. M., and Bone, R. C.
      (1985) J. Clin. Invest. 76, 500-507). To investigate the mechanisms underlying
      membrane conductance changes following human high affinity (FcgammaRI) receptor
      activation, we have used the human monocytic cell line U937 and combined
      conventional whole cell patch-clamp recordings with single cell fura-2 Ca2+
      measurements. Using a K+-free internal solution, antibody cross-linking of IgG
      occupied FcgammaRI activated an inward current at negative potentials, whose
      amplitude and time course mirrored the concomitant rise in intracellular Ca2+.
      Current-voltage relationships, obtained under different ionic conditions,
      revealed a monovalent cation-selective conductance that, under physiological
      conditions, would result in Na+ influx. Noise analysis of current recordings
      indicated a single channel conductance of 18 picosiemens and a mean opening time
      of 4.5 ms. This current was also activated by rises in intracellular Ca2+ induced
      by ionomycin (3 microM) or thapsigargin (1 microM). Addition of the Ca2+ chelator
      1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid to the intracellular
      medium abolished any channel activation by ionomycin, FcgammaRI, or the low
      affinity receptor, FcgammaRII. These results demonstrate that FcgammaRI
      activation triggers a novel Ca2+-activated channel selective for monovalent
      cations and that neither FcgammaRI nor FcgammaRII can directly activate a
      channel.

PMID- 9030529
TI  - The enethiolate anion reaction products of EpiD. Pka value of the enethiol side
      chain is lower than that of the thiol side chain of peptides.
AB  - One of the steps involved in the biosynthesis of the lantibiotic epidermin is the
      oxidative decarboxylation reaction of peptides catalyzed by the flavoenzyme EpiD.
      EpiD catalyzes the formation of a (Z)-enethiol derivative from the C-terminal
      cysteine residue of the precursor peptide of epidermin and related peptides. The
      UV-visible spectra of the reaction products of EpiD are pH-dependent, indicating
      that the enethiol side chain is converted to an enethiolate anion. The pKa value
      of the enethiol group was determined to be 6.0 and is substantially lower than
      the pKa value of the thiol side chain of cysteine residues. The increased acid
      strength of the enethiol side chain compared with that of the thiol group is
      attributed to the resonance stabilization of the negative charge of the anion.

PMID- 9030530
TI  - Subunit Ya-specific glutathione peroxidase activity toward cholesterol 7
      hydroperoxides of glutathione S-transferases in cytosols from rat liver and skin.
AB  - Dermal 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ols (cholesterol 7alpha-
      and 7beta-hydroperoxides), regarded as good aging markers in the rat (Ozawa, N.,
      Yamazaki, S., Chiba, K., Aoyama, H., Tomisawa, H., Tateishi, M., and Watabe, T.
      (1991) Biochem. Biophys. Res. Commun. 178, 242-247), were reduced in the presence
      of glutathione (GSH) with concomitant formation of GSSG by cytosol from rat liver
      in which no detectable level of the hydroperoxides had been demonstrated to
      occur. The GSH peroxidase (GSH Px) activity toward the toxic steroid
      hydroperoxides was exerted to almost the same extent by both Alpha-class GSH S
      transferases (GSTs), Ya-Ya and Ya-Yc, and by selenium-containing GSH Px (Se-GSH
      Px) in rat liver cytosol. None of three Mu-class GSTs, Yb1-Yb1, Yb1-Yb2, and Yb2
      Yb2, and a Theta-class GST, Yrs-Yrs, from rat liver and a Pi-class GST, Yp-Yp,
      from rat kidney showed any appreciable GSH Px activity toward the hydroperoxides.
      The subunit Ya-bearing GSTs and Se-GSH Px purified from rat liver cytosol showed
      marked differences in apparent specific activity toward the cholesterol
      hydroperoxides (GSTs Ya-Ya > Ya-Yc >> Se-GSH Px). However, a kinetic study
      indicated that Se-GSH Px had a higher affinity for steroid hydroperoxides than
      did the GSTs, so that Se-GSH Px could catalyze the reduction of lower
      concentrations of cholesterol 7-hydroperoxides with approximately equal Vmax/Km
      values to those by the GSTs. Rat skin had no GST bearing the subunit Ya but
      contained only a very low concentration of Se-GSH Px, possibly resulting in the
      accumulation of cholesterol 7-hydroperoxides in the skin but not in the liver.
      From rat skin cytosol, GSTs Yc-Yc, Yb1-Yb1, Yb1-Yb2, Yb2-Yb2, and Yp-Yp were
      isolated, purified to homogeneity, and identified with the corresponding GSTs
      from liver and kidney. The GSTs accounted for 0.23% of total skin cytosolic
      protein, and the most abundant isoform of skin GSTs was Yb2-Yb2, followed by Yc
      Yc, Yp-Yp, Yb1-Yb1, and Yb1-Yb2 in decreasing order.

PMID- 9030531
TI  - Molecular cloning of acetone cyanohydrin lyase from flax (Linum usitatissimum).
      Definition of a novel class of hydroxynitrile lyases.
AB  - Acetone cyanohydrin lyase from Linum usitatissimum is a hydroxynitrile lyase
      (HNL) which is involved in the catabolism of cyanogenic glycosides in young
      seedlings of flax. We have isolated a full-length cDNA clone encoding L.
      usitatissimum HNL (LuHNL) from a cDNA expression library by immunoscreening.
      LuHNL cDNA was expressed in Escherichia coli and isolated from the respective
      soluble fraction in an active form which was biochemically indistinguishable from
      the natural enzyme. An open reading frame of 1266 base pairs encodes for a
      protein of 45,780 kDa. The derived amino acid sequence shows no overall
      homologies to the to date cloned HNLs, but has significant similarities to
      members of the alcohol dehydrogenase (ADH) family of enzymes. In particular, the
      cysteine and histidine residues responsible for coordination of an active site
      Zn2+ and a second structurally important Zn2+ in alcohol dehydrogenases are
      conserved. Nevertheless, we found neither alcohol dehydrogenase activity in LuHNL
      nor HNL activity in ADH. Moreover, well known inhibitors of ADHs, which interfere
      with the coordination of the active site Zn2+, fail to affect HNL activity of
      LuHNL, suggesting principally different mechanisms of cyanohydrin cleavage and
      alcohol oxidation. Interestingly, LuHNL like ADH and Prunus serotina (PsHNL)
      possesses an ADP-binding betaalphabeta unit motif, pointing to the possibility
      that the non-flavoprotein PsHNL and the flavoprotein LuHNL have developed from
      two independent lines of evolution of a common ancestor with an ADP-binding
      betaalphabeta unit.

PMID- 9030532
TI  - Developmental regulation of a pregnancy-specific oligosaccharide structure,
      NeuAcalpha2,6GalNAcbeta1,4GlcNAc, on select members of the rat placental
      prolactin family.
AB  - Successful pregnancy is dependent upon an array of signaling proteins secreted by
      the trophoblast cells of the placenta. Among these is a group of proteins related
      to pituitary prolactin, known as the prolactin/growth hormone family. These
      proteins are expressed at specific times during gestation and synthesized in
      distinct trophoblast cell types in the rat placenta. We report here that select
      members of this family, prolactin-like protein (PLP-A), PLP-B, PLP-C,
      decidual/trophoblast PRP, and placental lactogen I variant, only which are
      expressed in the spongiotrophoblast, late in rat placental development bear Asn
      linked oligosaccharides terminating with NeuAcalpha2,6GalNAcbeta1,4GlcNAcbeta-R.
      This reflects the concurrent expression of these prolactin/growth hormone family
      members with the peptide-specific beta1,4GalNAc-transferase and an alpha2,6
      sialyltransferase, which can add sialic acid to terminal beta1,4-linked GalNAc.
      We have determined that at least one of the prolactin-like proteins, PLP-A, is
      recognized by the protein-specific GalNAc-transferase. The presence of
      NeuAcalpha2, 6GalNAcbeta1,4GlcNAcbeta-R on only a limited number of glycoproteins
      synthesized by the spongiotrophoblasts between mid gestation and birth reflects
      the need for both the GalNAc-transferase and the peptide recognition determinant
      for efficient addition of GalNAc. Thus, expression of the GalNAc-transferase and
      specific members of the prolactin/growth hormone family is developmentally
      regulated in the rat placenta, suggesting a physiological role for the terminal
      NeuAcalpha2,6GalNAcbeta1,4GlcNAcbeta-R sequence on Asn-linked oligosaccharides of
      these proteins.

PMID- 9030533
TI  - Fibronectin lacking the ED-B domain is a major structural component of tracheal
      cartilage.
AB  - Fibronectin is a highly conserved dimeric glycoprotein found in high
      concentrations in plasma and widely distributed in low concentrations in the
      extracellular matrix of tissues. The protein is the product of a single gene, but
      multiple splicing variants are expressed that show tissue specificity. Three
      exons (IIIA, IIIB, and V) can be alternatively spliced to produce different
      fibronectin isoforms. We report here that fibronectin is a remarkably abundant
      component of the extracellular matrix of bovine tracheal cartilage, increasing
      with age to more than 20% of the tissue, dry weight. This matrix form of
      fibronectin is inextractable by 4 M guanidine HCl, indicating that it is a
      covalently cross-linked structural component. By protein sequence analysis, the
      main molecular form of fibronectin in bovine tracheal cartilage was shown to lack
      the ED-B domain encoded by exon IIIB.

PMID- 9030534
TI  - Hyaluronan synthesis by mouse cumulus cells is regulated by interactions between
      follicle-stimulating hormone (or epidermal growth factor) and a soluble oocyte
      factor (or transforming growth factor beta1).
AB  - Expansion of the cumulus cell-oocyte complex (COC) in the preovulatory mammalian
      follicle requires a transient induction of hyaluronan (HA) synthesis by the
      cumulus cells. We studied the interactions of known factors that regulate this
      process by isolating compact COCs from mice and inducing their expansion in
      vitro. Maximum HA synthesis requires either follicle-stimulating hormone (FSH) or
      epidermal growth factor (EGF) in combination with either a soluble factor(s)
      produced by the oocyte or transforming growth factor beta1. FSH (or EGF) exerts
      its effects during the first 2 h of incubation, before HA synthesis actually
      begins. The oocyte factor(s) (or transforming growth factor beta1) exerts its
      effects from 2 h onwards and must be continuously present throughout the
      subsequent approximately 10 h to achieve a maximum level of HA synthesis. FSH
      stimulates intracellular cAMP synthesis, which correlates with net HA production
      up to approximately 14 fmol/COC at 5 ng/ml FSH; however, higher concentrations of
      FSH increase cAMP levels approximately 10-fold higher with no additional effect
      on HA synthesis. EGF at saturating concentrations for HA synthesis does not
      stimulate cAMP above basal levels. Tyrosine kinase inhibitors genistein and
      tyrphostin AG18 nearly abolish the HA synthesis response to EGF and inhibit the
      response to FSH by approximately 60%, suggesting that a tyrosine kinase activity
      is involved for both factors, whereas FSH also operates partially through another
      signaling pathway. Actinomycin D abolishes HA synthesis if added at the beginning
      of culture and reduces HA synthesis by approximately 50% if added between 6-12 h
      when HA synthesis is normally maximal. The results suggest that regulation of HA
      synthesis is primarily controlled at the transcriptional level.

PMID- 9030535
TI  - VMA11 and VMA16 encode second and third proteolipid subunits of the Saccharomyces
      cerevisiae vacuolar membrane H+-ATPase.
AB  - The vacuolar membrane H+-ATPase (V-ATPase) of the yeast Saccharomyces cerevisiae
      is composed of peripheral catalytic (V1) and integral membrane (V0) domains. The
      17-kDa proteolipid subunit (VMA3 gene product; Vma3p) is predicted to constitute
      at least part of the proton translocating pore of V0. Recently, two VMA3
      homologues, VMA11 and VMA16 (PPA1), have been identified in yeast, and VMA11 has
      been shown to be required for the V-ATPase activity. Cells disrupted for the
      VMA16 gene displayed the same phenotypes as those lacking either Vma3p or Vma11p;
      the mutant cells lost V-ATPase activity and failed to assemble V-ATPase subunits
      onto the vacuolar membrane. Epitope-tagged Vma11p and Vma16p were detected on the
      vacuolar membrane by immunofluorescence microscopy. Density gradient
      fractionation of the solubilized vacuolar proteins demonstrated that the tagged
      proteins copurified with the V-ATPase complex. We conclude that Vma11p and Vma16p
      are essential subunits of the V-ATPase. Vma3p contains a conserved glutamic acid
      residue (Glu137) whose carboxyl side chain is predicted to be important for
      proton transport activity. Mutational analysis of Vma11p and Vma16p revealed that
      both proteins contain a glutamic acid residue (Vma11p Glu145 and Vma16p Glu108)
      functionally similar to Vma3p Glu137. These residues could only be functionally
      substituted by an aspartic acid residue, because other mutations we examined
      inactivated the enzyme activity. Assembly and vacuolar targeting of the enzyme
      complex was not inhibited by these mutations. These results suggest that the
      three proteolipid subunits have similar but not redundant functions, each of
      which is most likely involved in proton transport activity of the enzyme complex.
      Yeast cells contain V0 and V1 subcomplexes in the vacuolar membrane and in the
      cytosol, respectively, that can be assembled into the active V0V1 complex in
      vivo. Surprisingly, loss-of-function mutations of either Vma11p Glu145 or Vma16p
      Glu108 resulted in a higher degree of assembly of the V1 subunits onto the V0
      subcomplex in the vacuolar membrane.

PMID- 9030536
TI  - Biophysical and biological properties of naturally occurring high molecular
      weight insulin-like growth factor II variants.
AB  - A soluble form of the insulin-like growth factor II/mannose 6-phosphate receptor
      (sIGF-II/MPR) is present in fetal bovine serum and carries mature 7.5-kDa insulin
      like growth factor II (IGF-II) and at least 12 different high molecular weight
      (Mr) IGF-II isoforms (Valenzano, K. J., Remmler, J., and Lobel, P. (1995) J.
      Biol. Chem. 270, 16441-16448). In this study, we used gel filtration and anion
      exchange chromatographies to resolve the isoforms into eight fractions that were
      characterized with respect to their biochemical, biophysical, and biological
      properties. Each fraction contained one to three major protein species with
      apparent sizes ranging from 11 to 17 kDa by SDS-polyacrylamide gel
      electrophoresis. The 11-kDa species contains no post-translational modifications
      and consists of an extended IGF-II backbone terminating at Gly-87. The remaining
      high Mr IGF-II isoforms are also composed of an 87-amino acid IGF-II peptide
      backbone but contain increasing amounts of sialated, O-linked sugars. Plasmon
      resonance spectroscopy experiments revealed that all the high Mr isoforms and
      mature 7.5-kDa IGF-II bound to immobilized recombinant soluble human IGF-I
      receptor, recombinant human IGF-binding protein 1, and sIGF-II/MPR with similar
      kinetics. In addition, radiolabeled tracer experiments demonstrated that both
      mature and high Mr IGF-II isoforms have similar binding profiles in fetal bovine
      serum and have similar affinities for IGF-II-binding proteins secreted from human
      fibroblasts. Finally, the biological activity of high Mr IGF-II was shown to be
      similar to or slightly better than mature IGF-II in stimulating amino acid uptake
      in fibroblasts and in inducing myoblast differentiation.

PMID- 9030537
TI  - Substrate specificity of hybrid modules from peptide synthetases.
AB  - Homologous modules from two different peptide synthetases were analyzed for
      functionally equivalent regions. Hybrids between the coding regions of the
      phenylalanine-activating module of tyrocidine synthetase and the valine
      activating module of surfactin synthetase were constructed by combining the two
      reading frames at various highly conserved consensus sequences. The resulting DNA
      fragments were expressed in Escherichia coli as C-terminal fusions to the gene
      encoding for the maltose-binding protein. The fusion proteins were purified, and
      the amino acid specificities, the acceptance of different nucleotide analogues,
      and the substrate binding affinities were analyzed. We found evidence for a large
      N-terminal domain and a short C-terminal domain of about 19 kDa within the two
      modules, which are separated by the sequence motif GELCIGG. The two domains could
      be reciprocally transferred between the two modules, and the constructed hybrid
      proteins showed amino acid adenylating activity. Hybrid proteins fused at various
      consensus motifs within the two domains were inactive, indicating that the
      domains may fold independently and represent complex functional units. The N
      terminal domain was found to be responsible for the amino acid specificity of the
      modules, and it is also involved in the recognition of the ribosyl and the
      phosphate moieties of the nucleotide substrate. For tyrocidine synthetase I, we
      could confine the sites for amino acid specificity to a region of 330 residues.
      The C-terminal domain is essential for the enzymatic activity and has a strong
      impact on the specific activity of the modules.

PMID- 9030538
TI  - Formation of DNA repair intermediates and incision by the ATP-dependent UvrB-UvrC
      endonuclease.
AB  - The Escherichia coli UvrB and UvrC proteins play key roles in DNA damage
      processing and incisions during nucleotide excision repair. To study the DNA
      structural requirements and protein-DNA intermediates formed during these
      processes, benzo[a]pyrene diol epoxide-damaged and structure-specific 50-base
      pair substrates were constructed. DNA fragments containing a preexisting 3'
      incision were rapidly and efficiently incised 5' to the adduct. Gel mobility
      shift assays indicated that this substrate supported UvrA dissociation from the
      UvrB-DNA complex, which led to efficient incision. Experiments with a DNA
      fragment containing an internal noncomplementary 11-base region surrounding the
      benzo[a]pyrene diol epoxide adduct indicated that UvrABC nuclease does not
      require fully duplexed DNA for binding and incision. In the absence of UvrA, UvrB
      (UvrC) bound to an 11-base noncomplementary region containing a 3' nick (Y
      substrate), forming a stable protein-DNA complex (Kd approximately 5-10 nM).
      Formation of this complex was absolutely dependent upon UvrC. Addition to this
      complex of ATP, but not adenosine 5'-(beta,gamma-iminotriphosphate) or adenosine
      5'-(beta, gamma-methylene)triphosphate, caused incision three or four nucleotides
      5' to the double strand-single strand junction. The ATPase activity of native
      UvrB is activated upon interaction with UvrC and enhanced further by the addition
      of Y substrate. Incision of this Y structure occurs even without DNA damage. Thus
      the UvrBC complex is a structure-specific, ATP-dependent endonuclease.

PMID- 9030539
TI  - A kappaB-related binding site is an integral part of the mts1 gene composite
      enhancer element located in the first intron of the gene.
AB  - The transcription of the mts1 gene correlates with the metastatic potential of
      mouse adenocarcinomas. Here we describe strong enhancer whose location coincides
      with the DNase I hypersensitivity area in the first intron of the mts1 gene. The
      investigation of the transcriptional activity of a series of plasmids bearing
      deletions in the first intron sequences revealed that the observed enhancer has a
      composite structure. The enhancer activity is partially formed by the kappaB
      related element: GGGGTTTTTCCAC. This sequence element was able to form several
      sequence-specific complexes with nuclear proteins extracted from both Mts1
      expressing CSML100 and Mts1-non-expressing CSML0 adenocarcinoma cells. Two of
      these complexes were identified as NF-kappaB/Rel-specific p50.p50 homo- and
      p50.p65 heterodimers. The third complex was formed by the 200-kDa protein. Even
      though the synthetic kappaB-responsible promoter was active in mouse
      adenocarcinoma cells, a mutation preventing NF-kappaB binding had no effect on
      the mts1 natural enhancer activity. On the contrary, the mutation in the kappaB
      related element, which abolished the binding of the 200-kDa protein, led to the
      functional inactivation of this site in the mts1 first intron. The mts1 kappaB
      like element activated transcription from its own mts1 gene promoter, as well as
      from the heterologous promoter in both CSML0 and CSML100 cells. However, in vivo
      occupancy of this site was observed only in Mts1-expressing CSML100 cells,
      suggesting the involvement of the described element in positive control of mts1
      transcription.

PMID- 9030540
TI  - Sphingosine mediates the immediate negative inotropic effects of tumor necrosis
      factor-alpha in the adult mammalian cardiac myocyte.
AB  - To determine whether activation of the neutral sphingomyelinase pathway was
      responsible for the immediate (<30 min) negative inotropic effects of tumor
      necrosis factor-alpha (TNF-alpha), we examined sphingosine levels in diluent and
      TNF-alpha-stimulated cardiac myocytes. TNF-alpha stimulation of adult feline
      cardiac myocytes provoked a rapid (<15 min) increase in the hydrolysis of
      [14C]sphingomyelin in cell-free extracts, as well as an increase in ceramide
      mass, consistent with cytokine-induced activation of the neutral sphingomyelinase
      pathway. High performance liquid chromatographic analysis of lipid extracts from
      TNF-alpha-stimulated cardiac myocytes showed that TNF-alpha stimulation produced
      a rapid (<30 min) increase in free sphingosine levels. Moreover, exogenous D
      sphingosine mimicked the effects of TNF-alpha on intracellular calcium
      homeostasis, as well as the negative inotropic effects of TNF-alpha in isolated
      contracting myocytes; time course studies showed that exogenous D-sphingosine
      produced abnormalities in cell shortening that were maximal at 5 min. Finally,
      blocking sphingosine production using an inhibitor of ceramidase, n
      oleoylethanolamine, completely abrogated the negative inotropic effects of TNF
      alpha in isolated contracting cardiac myocytes. Additional studies employing
      biologically active ceramide analogs and sphingosine 1-phosphate suggested that
      neither the immediate precursor of sphingosine nor the immediate metabolite of
      sphingosine, respectively, were likely to be responsible for the immediate
      negative inotropic effects of TNF-alpha. Thus, these studies suggest that
      sphingosine mediates the immediate negative inotropic effects of TNF-alpha in
      isolated cardiac myocytes.

PMID- 9030541
TI  - Cooperativity and dimerization of recombinant human estrogen receptor hormone
      binding domain.
AB  - The estrogen receptor dimerizes and exhibits cooperative ligand binding as part
      of its normal functioning. Interaction of the estrogen receptor with its ligands
      is mediated by a C-terminal hormone-binding domain (HBD), and residues within the
      HBD are thought to contribute to dimerization. To examine dimer interactions in
      the isolated HBD, a human estrogen receptor HBD fragment was expressed in high
      yield as a cleavable fusion protein in Escherichia coli. The isolated HBD peptide
      exhibited affinity for estradiol, ligand discrimination, and cooperative
      estradiol binding (Hill coefficient approximately 1.6) similar to the full-length
      protein. Circular dichroism spectroscopy suggests that the HBD contains
      significant amounts of alpha-helix ( approximately 60%) and some beta-strand (
      approximately 7%) and that ligand binding induces little change in secondary
      structure. HBD dimer dissociation, measured using size exclusion chromatography,
      exhibited a half-life of approximately 1.2 h, which ligand binding increased
      approximately 3-fold (estradiol) to approximately 4-fold (4-hydroxytamoxifen).
      These results suggest that the isolated estrogen receptor HBD dimerizes and
      undergoes conformational changes associated with cooperative ligand binding in a
      manner comparable to the full-length protein, and that one effect of ligand
      binding is to alter the receptor dimer dissociation kinetics.

PMID- 9030542
TI  - Reversible translocation of phosphoinositide 3-kinase to the cytoskeleton of ADP
      aggregated human platelets occurs independently of Rho A and without synthesis of
      phosphatidylinositol (3,4)-bisphosphate.
AB  - The aim of our study was to evaluate the effect of ADP and the role of
      cytoskeleton reorganization during reversible and irreversible platelet
      aggregation induced by ADP and thrombin, respectively, on the heterodimeric
      (p85alpha-p110) phosphoinositide 3-kinase translocation to the cytoskeleton and
      its activation. Reversible ADP-induced aggregation was accompanied by a
      reversible reorganization of the cytoskeleton and an increase in levels of the
      regulatory subunit p85alpha in this cytoskeleton similar to the increase observed
      in thrombin-activated platelets. This translocation followed a course parallel to
      the amplitude of aggregation. No increase in levels of both phosphatidylinositol
      (3, 4)-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol-(3,4,5)P3 could,
      however, be detected even at the maximum aggregation and PI 3-kinase alpha
      translocation. Moreover, in contrast to the situation for thrombin stimulation,
      the GTP-binding protein RhoA was hardly translocated to the cytoskeleton when
      platelets were stimulated with ADP, whereas translocation of pp60(c-)src and
      focal adhesion kinase did occur. These results suggest (i) translocation of
      signaling enzymes does not necessarily imply their activation, (ii) the
      reversibility of ADP-induced platelet aggregation may be the cause or the result
      of a lack of PI 3-kinase activation and hence of PtdIns(3,4)P2 production, and
      (iii) RhoA does not seem to be involved in the ADP activation pathway of
      platelets. Whether PtdIns(3,4)P2 or RhoA may contribute to the stabilization of
      platelet aggregates remains to be established.

PMID- 9030543
TI  - Signaling of the cardiotrophin-1 receptor. Evidence for a third receptor
      component.
AB  - Cardiotrophin-1 (CT-1) is a recently isolated cytokine belonging to the
      interleukin-6 cytokine family. In the present study we show that CT-1 activates
      its receptor expressed at the surface of a human neural cell line by recruiting
      gp130 and gp190/leukemia inhibitory factor receptor beta, as shown by analyzing
      their tyrosine phosphorylation level. Neutralizing antibody directed against
      gp130 and reconstitution experiments performed in the COS-7 cell line demonstrate
      that gp130-gp190 heterocomplex formation is essential for CT-1 signaling.
      Analysis of the subsequent activation events revealed that CT-1 induces and
      utilizes Jak1-, Jak2-, and Tyk2-associated tyrosine kinases, which are in turn
      relayed by STAT-3 transcription factor. Cross-linking of iodinated CT-1 to the
      cell surface led to the identification of a third alpha component in addition to
      gp130 and gp190, with an apparent molecular mass of 80 kDa. Removal of N-linked
      carbohydrates from the protein backbone of the alpha component resulted in a
      protein of 45 kDa. Our results provide evidence that the CT-1 receptor is
      composed of a tripartite complex, a situation similar to the high affinity
      receptor for ciliary neurotrophic factor.

PMID- 9030544
TI  - Molecular cloning and expression of cDNA encoding human 3'
      phosphoadenylylsulfate:galactosylceramide 3'-sulfotransferase.
AB  - We have isolated a cDNA clone encoding human 3'
      phosphoadenylylsulfate:galactosylceramide 3'-sulfotransferase (EC 2.8.2.11).
      Degenerate oligonucleotides, based on amino acid sequence data for the purified
      enzyme, were used as primers to amplify fragments of the gene from human renal
      cancer cell cDNA by the polymerase chain reaction method. The amplified cDNA
      fragment was then used as probe to screen a human renal cancer cell cDNA library.
      The isolated cDNA clone contained an open reading frame encoding 423 amino acids
      including all of the peptides that were sequenced. The deduced amino acid
      sequence predicts a type II transmembrane topology and contains two potential N
      glycosylation sites. There is no significant homology between this sequence and
      either the sulfotransferases cloned to date or other known proteins. Northern
      blot analysis demonstrated that a 1.9-kilobase mRNA was unique to renal cancer
      cells. When the cDNA was inserted into the expression vector pSVK3 and
      transfected into COS-1 cells, galactosylceramide sulfotransferase activity in the
      transfected cells increased from 8- to 16-fold over that of controls, and the
      enzyme product, sulfatide, was expressed on the transformed cells.

PMID- 9030545
TI  - The human POLD1 gene. Identification of an upstream activator sequence,
      activation by Sp1 and Sp3, and cell cycle regulation.
AB  - The promoter of the human POLD1 gene encoding the catalytic subunit of DNA
      polymerase delta is G/C-rich and does not contain a TATA box. Transient
      transfection analysis in HeLa cells employing POLD1-luciferase chimeric plasmids
      revealed a core promoter region extending 328 base pairs (bp) from the major
      transcription initiation site. Multiple elements in this region including two 11
      bp direct repeats located between nucleotide positions -92 and -22, play an
      important role in POLD1 promoter activity. Deletion or linker-replacement
      mutations of the repeats drastically reduced the promoter activity. A 70-bp DNA
      fragment containing the two repeats could stimulate the expression of the POLD1
      or a heterologous promoter in an orientation-independent manner. DNase I
      footprinting and band-shift assays showed that HeLa nuclear extracts contained
      proteins specifically binding to the repeat sequences. Southwestern blot and UV
      cross-linking analyses identified Sp1 and two 85-kDa proteins that bound to the
      repeats. Additionally, screening of HeLa cDNA expression libraries for the
      sequence-specific DNA-binding protein using the 11-bp repeat sequences as the
      probe, identified a cDNA that corresponds to Sp3, a member of the Sp1 family.
      Cotransfection studies in Drosophila SL2 cells showed that both Sp1 and Sp3, but
      not Sp2, could activate the POLD1 promoter through the repeat sequences. The
      POLD1 promoter activity was induced about 4-fold at the late G1/S boundary in
      serum-stimulated cells. The 11-bp repeats together with an E2F-like sequence,
      located adjacent to the major transcription initiation site, were important for
      the stimulation. Taken together, this study provides a direct evidence for
      transcriptional regulation of the human POLD1 gene.

PMID- 9030546
TI  - Specific aspects of electron transfer from adrenodoxin to cytochromes p450scc and
      p45011beta.
AB  - An analysis of the electron transfer kinetics from the reduced [2Fe-2S] center of
      bovine adrenodoxin and its mutants to the natural electron acceptors, cytochromes
      P450scc and P45011beta, is the primary focus of this paper. A series of mutant
      proteins with distinctive structural parameters such as redox potential,
      microenvironment of the iron-sulfur cluster, electrostatic properties, and
      conformational stability was used to provide more detailed insight into the
      contribution of the electronic and conformational states of adrenodoxin to the
      driving forces of the complex formation of reduced adrenodoxin with cytochromes
      P450scc and P45011beta and electron transfer. The apparent rate constants of
      P450scc reduction were generally proportional to the adrenodoxin redox potential
      under conditions in which the protein-protein interactions were not affected.
      However, the effect of redox potential differences was shown to be masked by
      structural and electrostatic effects. In contrast, no correlation of the
      reduction rates of P45011beta with the redox potential of adrenodoxin mutants was
      found. Compared with the interaction with P450scc, however, the hydrophobic
      protein region between the iron-sulfur cluster and the acidic site on the surface
      of adrenodoxin seems to play an important role for precise complementarity in the
      tightly associated complex with P45011beta.

PMID- 9030547
TI  - The tissue concentration of UDP-N-acetylglucosamine modulates the stimulatory
      effect of insulin on skeletal muscle glucose uptake.
AB  - To delineate the biochemical mechanism by which increased availability of GlcN
      impairs insulin action on skeletal muscle glucose uptake, we replenished the
      uridine pool during GlcN administration. Co-infusion of uridine with GlcN
      prevented the GlcN-induced fall in skeletal muscle UDP-glucose levels (24.9 +/-
      5. 3 versus 10.1 +/- 2.9 nmol/g; p < 0.01) and further increased the skeletal
      muscle UDP-GlcNAc levels (198.4 +/- 26.3 versus 96.0 +/- 8. 4 nmol/g; p < 0.01).
      Greater reductions in the rates of glucose infusion ( approximately 53%), glucose
      uptake ( approximately 43%), and glycogen synthesis ( approximately 60%) were
      observed with the addition of uridine. Similarly, the infusion of uridine alone
      markedly increased the skeletal muscle levels of both UDP-glucose (55.2 +/- 14.2
      versus 17.8 +/- 6.1 nmol/g; p < 0.01) and UDP-GlcNAc (86.8 +/- 8.8 versus 35.9 +/
      8.4 nmol/g; p < 0.05) and induced marked insulin resistance. The decrease in
      insulin action on peripheral glucose uptake was highly correlated with the
      increase in skeletal muscle UDP-GlcNAc levels. Finally, immunoisolation of GLUT4
      containing vesicles revealed that the rate of labeled GlcN incorporation was
      approximately 100-fold greater following GlcN compared with saline infusions (p <
      0.01). We suggest that the marked reduction in insulin action induced by GlcN and
      uridine is mediated by increased accumulation of muscle UDP-N-acetylhexosamines,
      perhaps via altered glycosylation of protein(s) in GLUT4-containing vesicles.

PMID- 9030548
TI  - Mutational analysis of a fatty acyl-coenzyme A synthetase signature motif
      identifies seven amino acid residues that modulate fatty acid substrate
      specificity.
AB  - Fatty acyl-CoA synthetase (fatty acid:CoA ligase, AMP-forming; EC 6.2.1.3)
      catalyzes the formation of fatty acyl-CoA by a two-step process that proceeds
      through the hydrolysis of pyrophosphate. In Escherichia coli this enzyme plays a
      pivotal role in the uptake of long chain fatty acids (C12-C18) and in the
      regulation of the global transcriptional regulator FadR. The E. coli fatty acyl
      CoA synthetase has remarkable amino acid similarities and identities to the
      family of both prokaryotic and eukaryotic fatty acyl-CoA synthetases, indicating
      a common ancestry. Most notable in this regard is a 25-amino acid consensus
      sequence, DGWLHTGDIGXWXPXGXLKIIDRKK, common to all fatty acyl-CoA synthetases for
      which sequence information is available. Within this consensus are 8 invariant
      and 13 highly conserved amino acid residues in the 12 fatty acyl-CoA synthetases
      compared. We propose that this sequence represents the fatty acyl-CoA synthetase
      signature motif (FACS signature motif). This region of fatty acyl-CoA synthetase
      from E. coli, 431NGWLHTGDIAVMDEEGFLRIVDRKK455, contains 17 amino acid residues
      that are either identical or highly conserved to the FACS signature motif.
      Eighteen site-directed mutations within the fatty acyl-CoA synthetase structural
      gene (fadD) corresponding to this motif were constructed to evaluate the
      contribution of this region of the enzyme to catalytic activity. Three distinct
      classes of mutations were identified on the basis of growth characteristics on
      fatty acids, enzymatic activities using cell extracts, and studies using purified
      wild-type and mutant forms of the enzyme: 1) those that resulted in either wild
      type or nearly wild-type fatty acyl-CoA synthetase activity profiles; 2) those
      that had little or no enzyme activity; and 3) those that resulted in lowering and
      altering fatty acid chain length specificity. Among the 18 mutants characterized,
      7 fall in the third class. We propose that the FACS signature motif is essential
      for catalytic activity and functions in part to promote fatty acid chain length
      specificity and thus may compose part of the fatty acid binding site within the
      enzyme.

PMID- 9030549
TI  - Dependence of activated Galpha12-induced G1 to S phase cell cycle progression on
      both Ras/mitogen-activated protein kinase and Ras/Rac1/Jun N-terminal kinase
      cascades in NIH3T3 fibroblasts.
AB  - We evaluated the roles of mitogen-activated protein kinase (MAPK) and Jun N
      terminal kinase (JNK) signaling cascades in Galpha12-induced G1 to S phase cell
      cycle progression in NIH3T3(M17) fibroblasts. Transient expression of a
      constitutively active mutant of Galpha12, Galpha12(R203C), resulted in a 2-fold
      increase in the number of bromodeoxyuridine-positive S phase cells over vector
      control level under serum-deprived conditions. Consistent with the ability of
      Galpha12(R203C) to induce G1/S transition, its expression led to a 2-fold
      increase in cyclin A promoter activity, which showed a marked synergism with a
      low concentration of serum, resulting in up to a 15-fold elevation over the basal
      level. In addition, Galpha12(R203C) caused a 2-fold stimulation in E2F-mediated
      transactivation. Wild type Galpha12 showed similar stimulatory effects on cyclin
      A promoter activity and E2F-mediated transactivation, although of lesser
      magnitude. We observed a modest but constitutive activation of MAPK in cells
      transfected with Galpha12(R203C), which was abolished by a dominant negative form
      of Ras. Galpha12(R203C) also induced a 3-fold increase in JNK activity, which was
      abolished by dominant negative forms of either Rac1 or Ras. The expression of
      dominant negative forms of Ras, MAPK, Rac1, or JNK inhibited Galpha12(R203C)
      induced increases in bromodeoxyuridine-positive cells. Also, the dominant
      negative forms of Ras, MAPK, and JNK strongly inhibited Galpha12(R203C)-induced
      stimulation of cyclin A promoter activity. These results demonstrate that both
      the Ras/MAPK and Ras/Rac1/JNK pathways convey necessary, if not sufficient,
      mitogenic signals induced by Galpha12 activation.

PMID- 9030550
TI  - Nuclear translocation of RhoA mediates the mitogen-induced activation of
      phospholipase D involved in nuclear envelope signal transduction.
AB  - In this paper we demonstrate for the first time a mitogen-induced activation of a
      nuclear acting phosphatidylcholine-phospholipase D (PLD) which is mediated, at
      least in part, by the translocation of RhoA to the nucleus. Addition of alpha
      thrombin to quiescent IIC9 cells results in an increase in PLD activity in IIC9
      nuclei. This is indicated by an increase in the alpha-thrombin-induced production
      of nuclear phosphatidylethanol in quiescent cells incubated in the presence of
      ethanol as well as an increase in PLD activity in isolated nuclei. Consistent
      with our previous report (Wright, T. M., Willenberger, S., and Raben, D. M.
      (1992) Biochem. J. 285, 395-400), the presence of ethanol decreases the alpha
      thrombin-induced production of phosphatidic acid without affecting the induced
      increase in nuclear diglyceride, indicating that the increase in nuclear PLD
      activity is responsible for the effect on phosphatidic acid, but not that on
      diglyceride. Our data further demonstrate that RhoA mediates the activation of
      nuclear PLD. RhoA translocates to the nucleus in response to alpha-thrombin.
      Additionally, PLD activity in nuclei isolated from alpha-thrombin-treated cells
      is reduced in a concentration-dependent fashion by incubation with RhoGDI and
      restored by the addition of prenylated RhoA in the presence of guanosine 5'-3-O
      (thio)triphosphate. Western blot analysis indicates that this RhoGDI treatment
      results in the extraction of RhoA from the nuclear envelope. These data support a
      role for a RhoA-mediated activation of PLD in our recently described hypothesis,
      which proposes that a signal transduction cascade exists in the nuclear envelope
      and represents a novel signal transduction cascade that we have termed NEST
      (nuclear envelope signal transduction).

PMID- 9030551
TI  - Cloning and characterization of a transcription factor that binds to the proximal
      promoters of the two mouse type I collagen genes.
AB  - We have used the yeast one-hybrid system to clone transcription factors that bind
      to specific sequences in the proximal promoters of the type I collagen genes. We
      utilized as bait the sequence between -180 and -136 in the pro-alpha2(I) collagen
      promoter because it acts as a functional promoter element and binds several DNA
      binding proteins. Three cDNA clones were isolated that encoded portions of the
      mouse SPR2 transcription factor, whereas a fourth cDNA contained a potential open
      reading frame for a polypeptide of 775 amino acids and was designated BFCOL1.
      Recombinant BFCOL1 was shown to bind to the -180 to -152 segment of the mouse pro
      alpha2(I) collagen proximal promoter and to two discrete sites in the proximal
      promoter of the mouse pro-alpha1(I) gene. The N-terminal portion of BFCOL1
      contains its DNA-binding domain. DNA transfection experiments using fusion
      polypeptides with the yeast GAL4 DNA-binding segment indicated that the C
      terminal part of BFCOL1 contained a potential transcriptional activation domain.
      We speculate that BFCOL1 participates in the transcriptional control of the two
      type I collagen genes.

PMID- 9030552
TI  - On the mechanism of D-amino acid oxidase. Structure/linear free energy
      correlations and deuterium kinetic isotope effects using substituted
      phenylglycines.
AB  - The kinetic mechanism of the reaction of D-amino acid oxidase (EC 1.4.3.3) from
      Trigonopsis variabilis with [alpha-1H]- and [alpha-2H]phenylglycine has been
      determined. The pH dependence of Vmax is compatible with pKa values of
      approximately 8.1 and >9.5, the former of which is attributed to a base which
      should be deprotonated for efficient catalysis. The deuterium isotope effect on
      turnover is approximately 3.9, and the solvent isotope effect approximately 1.6.
      The reductive half-reaction is biphasic, the first, fast phase, k2, corresponding
      to substrate dehydrogenation/enzyme flavin reduction and the second to
      conversion/release of product. Enzyme flavin reduction consists in an approach to
      equilibrium involving a finite rate for k-2, the reversal of k2. k2 is 28.8 and
      4.6 s-1 for [alpha-1H]- and [alpha-2H]phenylglycine, respectively, yielding a
      primary deuterium isotope effect approximately 6. The solvent deuterium isotope
      effect on the apparent rate of reduction for [alpha-1H]- and [alpha
      2H]phenylglycine is approximately 2.8 and approximately 5. The rates for k-2 are
      4.2 and 0.9 s-1 for [alpha-1H]- and [alpha-2H]phenylglycine, respectively, and
      the corresponding isotope effect is approximately 4.7. The isotope effect on
      alpha-H and the solvent one thus behave multiplicatively consistent with a highly
      concerted process and a symmetric transition state. The k2 and k-2 values for
      phenylglycines carrying the para substituents F, Cl, Br, CH3, OH, NO2 and OCH3
      have been determined. There is a linear correlation of k2 with the substituent
      volume VM and with sigma+; k-2 correlates best with sigma or sigma+ while steric
      parameters have little influence. This is consistent with the transition state
      being structurally similar to the product. The Bronsted plot of DeltaG versus
      DeltaG0 allows the estimation of the intrinsic DeltaG0 as approximately 58 kJ.M
      1. From the linear free energy correlations, the relation of DeltaG versus
      DeltaG0 and according to the theory of Marcus it is concluded that there is
      little if any development of charge in the transition state. This, together with
      the recently solved three-dimensional structure of D-amino acid oxidase from pig
      kidney (Mattevi, A., Vanoni, M.A., Todone, F., Rizzi, M., Teplyakov, A., Coda,
      A., Bolognesi, M., and Curti, B. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 7496
      7501), argues against a carbanion mechanism in its classical formulation. Our
      data are compatible with transfer of a hydride from the substrate alphaC-H to the
      oxidized flavin N(5) position, although, clearly, they cannot prove it.

PMID- 9030553
TI  - Roles of hydrogen bonding residues in the interaction between the alpha and beta
      subunits in the tryptophan synthase complex. Asn-104 of the alpha subunit is
      especially important.
AB  - The interaction of the alpha subunit with the beta2 subunit of tryptophan
      synthase is known to be necessary for the activation of each subunit and for the
      catalytic efficiency of the alpha2beta2 complex. To elucidate the roles of
      hydrogen bonds in the interaction site between the alpha and beta subunits for
      subunit association, eight mutant alpha subunits at five hydrogen bonding
      residues (N104D, N104A, N108D, N108A, E134A, E135A, N157D, and N157A) were
      constructed, and the thermodynamic parameters of association with the beta
      subunit were obtained using a titration calorimeter. The N104D and N104A
      mutations remarkably decreased the stimulation activities, the association
      constants, and the association enthalpies. Although the association constant and
      the stimulation activities of E134A were reduced in the absence of salt, the
      change in the association enthalpy was relatively small, and the addition of salt
      could repair its defects. The substitutions at positions 135 and 157 did not
      affect the stimulation activity and decreased the Gibbs energy of association
      corresponding to the defect in 1 mol of hydrogen bond. The present results
      suggest that the alpha subunit which has a mutation at position 104 cannot fold
      into an intact conformation upon complex formation, resulting in reduced
      stimulation activities. The hydrogen bond with Asn-104, which is a conserved
      residue among 16 microorganisms, was especially important for alpha/beta
      interaction and mutual activation.

PMID- 9030554
TI  - Effect of extracellular AMP on cell proliferation and metabolism of breast cancer
      cell lines with high and low glycolytic rates.
AB  - In differentiated tissues, such as muscle and brain, increased adenosine
      monophosphate (AMP) levels stimulate glycolytic flux rates. In the breast cancer
      cell line MCF-7, which characteristically has a constantly high glycolytic flux
      rate, AMP induces a strong inhibition of glycolysis. The human breast cancer cell
      line MDA-MB-453, on the other hand, is characterized by a more differentiated
      metabolic phenotype. MDA-MB-453 cells have a lower glycolytic flux rate and
      higher pyruvate consumption than MCF-7 cells. In addition, they have an active
      glycerol 3-phosphate shuttle. AMP inhibits cell proliferation as well as NAD and
      NADH synthesis in both MCF-7 and MDA-MB-453 cells. However, in MDA-MB-453 cells
      glycolysis is slightly activated by AMP. This disparate response of glycolytic
      flux rate to AMP treatment is presumably caused by the fact that the reduced NAD
      and NADH levels in AMP-treated MDA-MB-453 cells reduce lactate dehydrogenase but
      not cytosolic glycerol-3-phosphate dehydrogenase reaction. Due to the different
      enzymatic complement in MCF-7 cells, proliferation is inhibited under glucose
      starvation, whereas MDA-MB-453 cells grow under these conditions. The inhibition
      of cell proliferation correlates with a reduction in glycolytic carbon flow to
      synthetic processes and a decrease in phosphotyrosine content of several proteins
      in both cell lines.

PMID- 9030555
TI  - Interaction of human T-cell lymphotropic virus type I Tax, Ets1, and Sp1 in
      transactivation of the PTHrP P2 promoter.
AB  - We have previously shown that the parathyroid hormone-related protein (PTHrP)
      promoter contains binding sites for transcription factors Ets1 and Sp1 and that
      human T-cell lymphotropic virus type I (HTLV-I) Tax cooperates with Ets1 to
      transactivate the PTHrP P2 promoter. Using the yeast two-hybrid interaction
      system, we now provide evidence that Tax interacts with Ets1. Moreover, a double
      mutation (D22A,C23S) in the Tax protein that abrogated the Tax/Ets1 interaction
      also inhibited the Tax/Ets1 cooperative effect, suggesting that the interaction
      between Tax and Ets1 is important for transactivation of the PTHrP promoter. In
      coimmunoprecipitation assays, we find that Tax facilitates the interaction
      between Ets1 and Sp1, forming a ternary complex. When the Sp1 site in the PTHrP
      promoter was mutated, the Tax/Ets1 cooperative effect was dramatically decreased.
      This suggests that Sp1 plays an important role in the Ets1-dependent Tax
      transactivation of the PTHrP P2 promoter. Finally, we demonstrate that Gal4-Tax
      is a strong activator of the Gal PTHrP promoter, implying that Tax contributes
      directly to the transcriptional activation of the promoter. We propose a model in
      which the Tax/Ets1 cooperative effect on the PTHrP P2 promoter is based on the
      ability of Tax, Ets1, and Sp1 to form a ternary complex on the template DNA. Tax
      facilitates the interaction of Ets1/Sp1 and participates directly in the
      transcription initiation process.

PMID- 9030556
TI  - 1400W is a slow, tight binding, and highly selective inhibitor of inducible
      nitric-oxide synthase in vitro and in vivo.
AB  - N-(3-(Aminomethyl)benzyl)acetamidine (1400W) was a slow, tight binding inhibitor
      of human inducible nitric- oxide synthase (iNOS). The slow onset of inhibition by
      1400W showed saturation kinetics with a maximal rate constant of 0.028 s-1 and a
      binding constant of 2.0 microM. Inhibition was dependent on the cofactor NADPH. L
      Arginine was a competitive inhibitor of 1400W binding with a Ks value of 3.0
      microM. Inhibited enzyme did not recover activity after 2 h. Thus, 1400W was
      either an irreversible inhibitor or an extremely slowly reversible inhibitor of
      human iNOS with a Kd value </= 7 nM. In contrast, inhibition of human neuronal
      NOS and endothelial NOS (eNOS) was relatively weaker, rapidly reversible, and
      competitive with L-arginine, with Ki values of 2 microM and 50 microM,
      respectively. Thus, 1400W was at least 5000-fold selective for iNOS versus eNOS.
      This selectivity was similar to that observed in rat aortic rings, in which 1400W
      was greater than 1000-fold more potent against rat iNOS than eNOS. Finally, 1400W
      was greater than 50-fold more potent against iNOS than eNOS in a rat model of
      endotoxin-induced vascular injury. Thus, the potency and selectivity of 1400W
      inhibition of iNOS both in vitro and in vivo were far greater than of any
      previously described iNOS inhibitor.

PMID- 9030557
TI  - Activation of a calcium-permeable cation channel CD20 expressed in Balb/c 3T3
      cells by insulin-like growth factor-I.
AB  - CD20 functions as a calcium-permeable cation channel. When expressed in Balb/c
      3T3 cells, CD20 accelerates the G1 progression induced by insulin-like growth
      factor-I (IGF-I). To further characterize how CD20 modulates the action of IGF-I,
      we investigated whether the activity of CD20 channel was affected by IGF-I. In
      quiescent cells expressing CD20, IGF-I increased cytoplasmic free calcium
      concentration, [Ca2+]c, which was reversed by the removal of extracellular
      calcium. In contrast, IGF-I did not increase [Ca2+]c in cells that did not
      express CD20. In perforated patch clamp recordings, addition of IGF-I to the bath
      solution augmented the Ca2+ permeability, which was reversed by anti-CD20
      antibody. In cell-attached patch, calcium-permeable channel activity with unitary
      conductance of 7 picosiemens was detected, which was abolished by anti-CD20
      antibody. The single channel activities were markedly enhanced when IGF-I was
      included in the pipette solution, whereas IGF-I added to the bath solution was
      ineffective. When cells were first exposed to pertussis toxin, activation of the
      channel by IGF-I was blocked. Transfection of cDNA for Gip2, a constitutive
      active form of alphai2, activated the CD20 channel. These results indicate that
      the CD20 channel is regulated by the IGF-I receptor by a mechanism involving
      pertussis toxin-sensitive G protein.

PMID- 9030558
TI  - Protein kinase C inhibits adenylyl cyclase type VI activity during
      desensitization of the A2a-adenosine receptor-mediated cAMP response.
AB  - We have previously reported that phosphorylation of adenylyl cyclase type VI
      (AC6) may result in the suppression of adenylyl cyclase activity during
      desensitization of the A2a-adenosine receptor-mediated cAMP response (A2a
      desensitization) in rat pheochromocytoma PC12 cells. In the present study, we
      demonstrate that protein kinase C (PKC) is responsible for the phosphorylation
      and inhibition of AC6 during A2a desensitization. Inhibition of PKC by several
      independent methods markedly blocked the suppression of AC6 during A2a
      desensitization. Purified PKC from rat brain directly phosphorylated and
      inhibited recombinant AC6 expressed in Sf21 cells. Substantially lower AC6
      activities were also observed in PC12 cells overexpressing PKCdelta or
      PKCepsilon. Stimulation of A2a-R in PC12 cells under the same conditions as those
      required for A2a desensitization resulted in an increase in Ca2+-independent PKC
      activity. Most importantly, exogenous PKC did not further suppress AC6 activity
      in A2a-desensitized membranes. In vitro PKC phosphorylation of AC6 isolated from
      A2a-desensitized cells was also profoundly lower than that from control cells,
      suggesting a specific role for PKC in regulating AC6 during A2a desensitization
      in PC12 cells. Taken together, our data demonstrate that a calcium-independent,
      novel PKC inhibits AC6 activity during A2a desensitization in PC12 cells.
      Independent regulation of AC6 by calcium-independent PKC and by Ca2+ provides an
      exquisite mechanism for integrating signaling pathways to fine-tune cAMP
      synthesis.

PMID- 9030559
TI  - Phosphorylation by protein kinase C is required for acute activation of cystic
      fibrosis transmembrane conductance regulator by protein kinase A.
AB  - Protein kinase A (PKA) stimulates Cl secretion by activating the cystic fibrosis
      transmembrane conductance regulator (CFTR), a tightly regulated Cl- channel in
      the apical membrane of many secretory epithelia. The CFTR channel is also
      modulated by protein kinase C (PKC), but the regulatory mechanisms are poorly
      understood. Here we present evidence that PKA-mediated phosphorylation alone is
      not a sufficient stimulus to open the CFTR chloride channel in the presence of
      MgATP; constitutive PKC phosphorylation is essential for acute activation of CFTR
      by PKA. When patches were excised from transfected Chinese hamster ovary cells,
      CFTR responses to PKA became progressively smaller with time and eventually
      disappeared. This decline in PKA responsiveness did not occur in the presence of
      exogenous PKC and was reversed by the addition of PKC to channels that had become
      refractory to PKA. PKC enhanced PKA stimulation of open probability without
      increasing the number of functional channels. Short-term pretreatment of cells
      with the PKC inhibitor chelerythrine (1 microM) reduced the channel activity that
      could be elicited by forskolin in cell-attached patches. Moreover, in whole cell
      patches, acute stimulation of CFTR currents by chlorophenylthio-cAMP was
      abolished by two chemically unrelated PKC inhibitors, although an abrupt, partial
      activation was observed after a delay of >15 min. Modulation by PKC was most
      pronounced when basal PKC phosphorylation was reduced by briefly preincubating
      cells with chelerythrine. Constitutive PKC phosphorylation in unstimulated cells
      permits the maximum elevation of open probability by PKA to reach a level that is
      approximately 60% of that attained during in vitro exposure to both kinases.
      Differences in basal PKC activity may contribute to the variable cAMP
      responsiveness of CFTR channels in different cell types.

PMID- 9030560
TI  - Mutagenesis studies of the human erythropoietin receptor. Establishment of
      structure-function relationships.
AB  - Mutagenesis of the erythropoietin receptor (EPOR) permits analysis of the
      contribution that individual amino acid residues make to erythropoietin (EPO)
      binding. We employed both random and site-specific mutagenesis to determine the
      function of amino acid residues in the extracellular domain (referred to as EPO
      binding protein, EBP) of the EPOR. Residues were chosen for site-specific alanine
      substitution based on the results of the random mutagenesis or on their homology
      to residues that are conserved or have been reported to be involved in ligand
      binding in other receptors of the cytokine receptor family. Site-specific mutants
      were expressed in Escherichia coli as soluble EBP and analyzed for EPO binding in
      several different assay formats. In addition, selected mutant proteins were
      expressed as full-length EPOR on the surface of COS cells and analyzed for 125I
      EPO binding in receptor binding assays. Using these methods, we have identified
      residues that appear to be involved in EPO binding as well as other residues,
      most of which are conserved in receptors of the cytokine receptor family, that
      appear to be necessary for the proper folding and/or stability of the EPOR. We
      present correlations between these mutagenesis data and the recently solved
      crystal structure of the EBP with a peptide ligand.

PMID- 9030561
TI  - Chimeric erythropoietin-interferon gamma receptors reveal differences in
      functional architecture of intracellular domains for signal transduction.
AB  - Binding of interferon gamma (IFN-gamma) causes oligomerization of the two
      interferon gamma receptor (IFN-gammaR) subunits, receptor chain 1 (IFN-gammaR1,
      the ligand-binding chain) and the second chain of the receptor (IFN-gammaR2), and
      causes activation of two Jak kinases (Jak1 and Jak2). In contrast, the
      erythropoietin receptor (EpoR) requires only one receptor chain and one Jak
      kinase (Jak2). Chimeras between the EpoR and the IFN-gammaR1 and IFN-gammaR2
      chains demonstrate that the architecture of the EpoR and the IFN-gammaR complexes
      differ significantly. Although IFN-gammaR1 alone cannot initiate signal
      transduction, the chimera EpoR/gammaR1 (extracellular/intracellular) generates
      slight responses characteristic of IFN-gamma in response to Epo and the
      EpoR/gammaR1. EpoR/gammaR2 heterodimer is a fully functional receptor complex.
      The results demonstrate that the configuration of the extracellular domains
      influences the architecture of the intracellular domains.

PMID- 9030562
TI  - Crystal structures of CheY mutants Y106W and T87I/Y106W. CheY activation
      correlates with movement of residue 106.
AB  - Position 106 in CheY is highly conserved as an aromatic residue in the response
      regulator superfamily. In the structure of the wild-type, apo-CheY, Tyr106 is a
      rotamer whose electron density is observed in both the inside and the outside
      positions. In the structure of the T87I mutant of CheY, the threonine to
      isoleucine change at position 87 causes the side chain of Tyr106 to be
      exclusively restricted to the outside position. In this report we demonstrate
      that the T87I mutation causes cells to be smooth swimming and non-chemotactic. We
      also show that another CheY mutant, Y106W, causes cells to be more tumbly than
      wild-type CheY, and impairs chemotaxis. In the structure of Y106W, the side chain
      of Trp106 stays exclusively in the inside position. Furthermore, a T87I/Y106W
      double mutant, which confers the same phenotype as T87I, restricts the side chain
      of Trp106 to the outside position. The results from these behavioral and
      structural studies indicate that the rotameric nature of the Tyr106 residue is
      involved in activation of the CheY molecule. Specifically, CheY's signaling
      ability correlates with the conformational heterogeneity of the Tyr106 side
      chain. Our data also suggest that these mutations affect the signal at an event
      subsequent to phosphorylation.

PMID- 9030563
TI  - Misregulation of stromelysin-1 expression in mouse mammary tumor cells
      accompanies acquisition of stromelysin-1-dependent invasive properties.
AB  - Stromelysin-1 is a member of the metalloproteinase family of extracellular matrix
      degrading enzymes that regulates tissue remodeling. We previously established a
      transgenic mouse model in which rat stromelysin-1 targeted to the mammary gland
      augmented expression of endogenous stromelysin-1, disrupted functional
      differentiation, and induced mammary tumors. A cell line generated from an
      adenocarcinoma in one of these animals and a previously described mammary tumor
      cell line generated in culture readily invaded both a reconstituted basement
      membrane and type I collagen gels, whereas a nonmalignant, functionally normal
      epithelial cell line did not. Invasion of Matrigel by tumor cells was largely
      abolished by metalloproteinase inhibitors, but not by inhibitors of other
      proteinase families. Inhibition experiments with antisense oligodeoxynucleotides
      revealed that Matrigel invasion of both cell lines was critically dependent on
      stromelysin-1 expression. Invasion of collagen, on the other hand, was reduced by
      only 40-50%. Stromelysin-1 was expressed in both malignant and nonmalignant cells
      grown on plastic substrata. Its expression was completely inhibited in
      nonmalignant cells, but up-regulated in tumor cells, in response to Matrigel.
      Thus misregulation of stromelysin-1 expression appears to be an important aspect
      of mammary tumor cell progression to an invasive phenotype.

PMID- 9030564
TI  - Pyruvate-extended amino acid derivatives as highly potent inhibitors of carboxyl
      terminal peptide amidation.
AB  - Carboxyl-terminal amidation, a required post-translational modification for the
      bioactivation of many neuropeptides, entails sequential enzymatic action by
      peptidylglycine monooxygenase (PAM, EC 1.14.17.3) and peptidylamidoglycolate
      lyase (PGL, EC 4.3.2.5). The monooxygenase, PAM, first catalyzes conversion of a
      glycine-extended pro-peptide to the corresponding alpha-hydroxyglycine
      derivative, and the lyase, PGL, then catalyzes breakdown of this alpha
      hydroxyglycine derivative to the amidated peptide plus glyoxylate. We now
      introduce the first potent inhibitors for peptidylamidoglycolate lyase. These
      inhibitors, which can be viewed as pyruvate-extended N-acetyl amino acids,
      constitute a novel class of compounds. They were designed to resemble likely
      transient species along the reaction pathway of PGL catalysis. A general
      synthetic procedure for preparation of pyruvate-extended N-acetyl amino acids or
      peptides is described. Since these compounds possess the 2,4-dioxo-carboxylate
      moiety, their solution tautomerization was investigated using both NMR and high
      performance liquid chromatography analyses. The results establish that freshly
      prepared solutions of N-Ac-Phe-pyruvate consist predominantly of the enol
      tautomer, which then slowly tautomerizes to the diketo form when left standing
      for several days in an aqueous medium; upon acidification, formation of the
      hydrate tautomer occurs. Kinetic experiments established that these novel
      compounds are highly potent, pure competitive inhibitors of PGL. Kinetic
      experiments with the ascorbate-dependent copper monooxygenases, PAM and dopamine
      beta-monooxygenase, established that these compounds also bind competitively with
      respect to ascorbate; however, pyruvate-extended N-acyl-amino acid derivatives
      possessing hydrophobic side chains are much more potent inhibitors of PGL than of
      PAM. Selective targeting of N-Ac-Phe-pyruvate so as to inhibit the lyase, but not
      the monooxygenase, domain was demonstrated with the bifunctional amidating enzyme
      of Xenopus laevis. The availability of potent inhibitors of PGL should facilitate
      studies regarding the possible biological role of alpha-hydroxyglycine-extended
      peptides.

PMID- 9030565
TI  - Identification of an insulin-responsive element in the rat insulin-like growth
      factor-binding protein-3 gene.
AB  - The hepatic expression and serum levels of insulin-like growth factor-binding
      protein-3 (IGFBP-3) are decreased in insulin-dependent and insulin-resistant
      diabetes. Insulin increases hepatic IGFBP-3 expression by enhancing gene
      transcription. This report identifies sequences within the IGFBP-3 promoter that
      are necessary and sufficient for the response to insulin in hepatic
      nonparenchymal cells. By transient transfection, we mapped the insulin response
      element to the -1150 to -1124 base pair (bp) region of the rat IGFBP-3 promoter.
      Three tandem repeats of the -1150 to -1117 bp region conferred insulin responses
      in a heterologous promoter. Gel shift analyses revealed a 3-fold increase in DNA
      protein complex formation with nuclear extracts obtained from insulin-stimulated
      nonparenchymal cells compared with cells incubated without insulin and revealed 3
      4-fold decrease in complex formation with nuclear extracts obtained from the
      livers of streptozotocin-diabetic rats compared with control rats. Mutational
      analysis of this 34-bp region showed a core sequence of 10 bp (-1148 to -1139)
      that is critical for interaction with insulin-induced trans-acting factors.
      Southwestern blotting revealed a approximately 90-kDa protein that was increased
      2-3-fold by the addition of insulin. Thus, we have identified cis-acting DNA
      sequences that are responsible for regulation of IGFBP-3 transcription by insulin
      and essential for binding of insulin-responsive nuclear factors.

PMID- 9030566
TI  - Intracellular assembly and degradation of apolipoprotein B-100-containing
      lipoproteins in digitonin-permeabilized HEP G2 cells.
AB  - Permeabilized Hep G2 cells have been used to investigate the turnover of
      apolipoprotein B-100 (apoB-100). When such cells were chased in the presence of
      buffer, there was no biosynthesis of apoB-100, nor was the protein secreted from
      the cells. Thus the turnover of apoB-100 in these cells reflected the
      posttranslational degradation of the protein. Pulse-chase studies indicated that
      apoB-100 was degraded both when associated with the membrane and when present as
      lipoproteins in the secretory pathway. Neither albumin nor alpha1-antitrypsin
      showed any significant posttranslational intracellular degradation under the same
      condition. The kinetics for the turnover of apoB-100 in the luminal content
      differed from that of apoB-100 that was associated with the microsomal membrane.
      Moreover, while the degradation of the luminal apoB-100 was inhibited by N-acetyl
      leucyl-leucyl-norleucinal (ALLN), this was not the case for the membrane
      associated protein. Together these results suggest the existence of different
      pathways for the degradation of luminal apoB-100 and membrane-associated apoB
      100. This was further supported by results from pulse-chase studies in intact
      cells, showing that ALLN increased the amount of radioactive apoB-100 that
      associated with the microsomal membrane during the pulse-labeling of the cells.
      However, ALLN did not influence the rate of turnover of the membrane-associated
      apoB-100. The presence of an ATP-generating system during the chase of the
      permeabilized cells prevented the disappearance of pulse-labeled apoB-100 from
      the luminal lipoprotein-associated pool. The ATP-generating system combined with
      cytosol protected the total apoB-100 in the system from being degraded. The cells
      cultured in the presence of oleic acid and chased after permeabilization in the
      presence of cytosol and the ATP-generating system showed an increase in the
      amount of apoB-100 present on dense ("high density lipoprotein-like") particles.
      This increase was linear during the time investigated (i. e. from 0 to 2 h chase)
      and independent of protein biosynthesis. Our results indicate that the dense
      particle was generated by a redistribution of apoB-100 within the secretory
      pathway and that it most likely was assembled from the membrane- associated form
      of apoB-100. These results indicate that the release of apoB-100 from this
      membrane-associated form to the microsomal lumen is dependent on cytosolic
      factors and a source of metabolic energy.

PMID- 9030567
TI  - Opiate-induced adenylyl cyclase superactivation is isozyme-specific.
AB  - While acute activation of inhibitory Gi/o-coupled receptors leads to inhibition
      of adenylyl cyclase, chronic activation of such receptors leads to an increase in
      cAMP accumulation. This phenomenon, observed in many cell types, has been
      referred to as adenylyl cyclase superactivation. At this stage, the mechanism
      leading to adenylyl cyclase superactivation and the nature of the isozyme(s)
      responsible for this phenomenon are largely unknown. Here we show that
      transfection of adenylyl cyclase isozymes into COS-7 cells results in an isozyme
      specific increase in AC activity upon stimulation (e.g. with forskolin,
      ionomycin, or stimulatory receptor ligands). However, independently of the method
      used to activate specific adenylyl cyclase isozymes, acute activation of the mu
      opioid receptor inhibited the activity of adenylyl cyclases I, V, VI, and VIII,
      while types II, IV, and VII were stimulated and type III was not affected.
      Chronic mu-opioid receptor activation followed by removal of the agonist was
      previously shown, in transfected COS-7 cells, to induce superactivation of
      adenylyl cyclase type V. Here we show that it also leads to superactivation of
      adenylyl cyclase types I, VI, and VIII, but not of type II, III, IV, or VII,
      demonstrating that the superactivation is isozyme-specific. Not only were
      isozymes II, IV, and VII not superactivated, but a reduction in the activities of
      these isozymes was actually observed upon chronic opiate exposure. These results
      suggest that the phenomena of tolerance and withdrawal involve specific adenylyl
      cyclase isozymes.

PMID- 9030568
TI  - Influence of allelic variation on apolipoprotein(a) folding in the endoplasmic
      reticulum.
AB  - Plasma levels of lipoprotein(a) (Lp(a)) vary over 1000-fold between individuals
      and are determined by the gene for its unique apolipoprotein, apo(a), which has
      greater than 100 alleles. Using primary baboon hepatocyte cultures, we previously
      demonstrated that differences in the ability of apo(a) allelic variants to escape
      the endoplasmic reticulum (ER) are a major determinant of Lp(a) production rate.
      To examine the reason for these differences, the folding of newly synthesized
      apo(a) was analyzed in pulse-chase experiments. Samples were harvested in the
      presence of N-ethylmaleimide to preserve disulfide-bonded folding intermediates,
      and apo(a) was analyzed by immunoprecipitation and SDS-polyacrylamide gel
      electrophoresis. Apo(a) required a prolonged period (30-60 min) to reach its
      fully oxidized form. Multiple folding intermediates were resolved, including a
      disulfide-linked, apo(a)-containing complex. Unexpectedly, all allelic variants
      examined showed similar patterns and kinetics of folding. Even "null" apo(a)
      proteins, which are unable to exit the ER, appeared to fold normally. The ER
      glucosidase inhibitor, castanospermine, prevented apo(a) secretion, but did not
      inhibit folding. This suggests that an event which is dependent on trimming of N
      linked glucoses, and which occurs after the folding events detectable in our
      assay, is required for apo(a) secretion. Differences in the ability to undergo
      this event may explain the variable efficiency with which apo(a) allelic variants
      exit the ER.

PMID- 9030569
TI  - Novel repeat elements direct rat proenkephalin transcription during
      spermatogenesis.
AB  - The developmental program controlling sperm formation occurs in multiple stages
      that sequentially involve mitosis, meiosis, and spermiogenesis. The
      transcriptional mechanisms regulating these distinct phases are poorly
      understood. In particular, while a required role for the germ cell transcription
      factor cyclic AMP response element modulator-tau during spermiogenesis has
      recently been demonstrated, the transcriptional mechanisms leading to early
      haploid cell formation are unknown. The rat and mouse proenkephalin genes are
      selectively expressed from an alternate, germ cell-specific promoter in meiotic
      and early haploid cells. In this study, the minimal rat proenkephalin germ line
      promoter was localized to a 116-bp region encompassing the transcriptional start
      site region. Further, a proximal 51-bp sequence located in the 5'-flanking region
      is absolutely required for germ line promoter activity. This 51 bp sequence
      corresponds to a previously characterized binding element (GCP1) that forms cell
      specific complexes with rat spermatogenic cell nuclear factors distinct from
      cyclic AMP response element binding proteins. Further, GCP1 contains novel direct
      repeat sequences required for factor binding and transgene expression in
      spermatogenic cells. These repeat elements are highly similar to sequences within
      the active regions of other male germ line promoters expressed during meiosis.
      GCP1 may therefore contain transcriptional elements that participate more
      generally during meiosis in the differentiation of spermatocytes and early
      haploid spermatids.

PMID- 9030570
TI  - Cyclic GMP causes Ca2+ desensitization in vascular smooth muscle by activating
      the myosin light chain phosphatase.
AB  - Using permeabilized, arterial smooth muscle strips where membrane-associated
      pathways remain intact but intracellular Ca2+ stores are depleted, we
      investigated mechanism(s) for the Ca2+ desensitization of contractile force by
      cGMP. The nonhydrolyzable analog 8-bromo-cGMP, when applied to these strips with
      submaximal Ca2+ levels clamped, dramatically and reversibly reduced the steady
      state levels of phosphorylation at 20-kDa myosin light chain and contractile
      force, with a nanomolar concentration required to obtain 50% reduction.
      Supramaximal concentrations of 8-bromo-cGMP (10 microM), however, did not change
      the steady state relationship between phosphorylation and force. When light chain
      phosphatase activity was blocked at pCa 6.7, 10 microM 8-bromo-cGMP did not
      affect the rates of rise of light chain phosphorylation and contractile force.
      When light chain kinase activity was blocked, 10 microM 8-bromo-cGMP
      significantly accelerated light chain dephosphorylation and force relaxation from
      the maximal contraction steady state. The light chain phosphorylation time course
      of a pCa 6. 0-induced contraction in the presence of 8-bromo-cGMP exhibited
      kinetics that are predictable from a mathematical model in which only light chain
      phosphatase activity is increased. The results of this study strongly suggest
      that cGMP indirectly activates light chain phosphatase, the first proposed
      mechanism for cGMP-induced Ca2+ desensitization in vasodilatation.

PMID- 9030571
TI  - Different residues of the human estrogen receptor are involved in the recognition
      of structurally diverse estrogens and antiestrogens.
AB  - We have previously examined, by alanine scanning mutagenesis, amino acids 515-535
      of the estrogen receptor (ER) ligand binding domain to determine which of these
      residues are important in estradiol binding. Mutation at four sites that
      potentially lie along one face of an alpha-helix, Gly521, His524, Leu525, and
      Met528, all significantly impaired estradiol binding by the ER (Ekena, K., Weis,
      K. E., Katzenellenbogen, J. A., and Katzenellenbogen, B. S. (1996) J. Biol. Chem.
      271, 20053-20059). In this report, we compare the pattern of residues that are
      important in the recognition of several structurally diverse estrogen agonists
      and antagonists (the synthetic nonsteroidal agonist hexestrol, an agonist derived
      from the mold metabolite zearalenone, P1496, and the partial agonist-antagonist
      trans-hydroxytamoxifen) with those that are predicted to contact estradiol in the
      receptor-ligand complex. Although there are some similarities in the pattern of
      residue recognition among all four ligands, each ligand showed distinct
      differences as well. Interestingly, alanine substitution at only one residue, the
      leucine at position 525, was found to inhibit binding of all the ligands tested.
      Another residue, His524, was found to be important in the recognition of three
      different agonists but not trans-hydroxytamoxifen (the only ligand lacking a
      second hydroxyl group). The recognition of estradiol and another agonist, P1496,
      was impaired by the G521A mutation, whereas ligand-induced activity by the two
      compounds that lack B- and C-rings, hexestrol and trans-hydroxytamoxifen, was
      unaffected. Our findings demonstrate that these ligands fit into the ER ligand
      binding pocket differently and that each contacts a distinct set of amino acids.
      The smaller ligands (estradiol and hexestrol) have a narrower footprint of
      interacting residues than the larger ligands (P1496 and trans-hydroxytamoxifen).
      This pattern of interaction is most consistent with the amino acids within this
      region being in contact with the portion of these ligands that corresponds to the
      D-ring end of estradiol. The interplay between the shape of an ER ligand and the
      residues that support its binding to ER may potentially underlie the selective
      actions of different ER ligands in various cell and promoter contexts.

PMID- 9030572
TI  - Importance of the dimer-dimer interface for allosteric signal transduction and
      AMP cooperativity of pig kidney fructose-1,6-bisphosphatase. Site-specific
      mutagenesis studies of Glu-192 and Asp-187 residues on the 190's loop.
AB  - The role of the 190's loop of fructose-1,6-bisphosphatase (Fru-1, 6-P2ase) in the
      allosteric regulation of Fru-1,6-P2ase has been investigated through kinetic
      studies on three mutant enzymes, Glu-192 --> Ala, Glu-192 --> Gln, and Asp-187 -
      > Ala. AMP is an allosteric inhibitor, which binds to the regulatory sites and
      induces the R- to T-state transition; for wild-type Fru-1,6-P2ase AMP inhibition
      is cooperative with a Hill coefficient of 2.0. The replacement of Asp-187, which
      forms an interaction across the C1:C2 monomer-monomer interface, with alanine did
      not change the catalytic efficiency, and it had no effect on the cooperativity of
      AMP inhibition; however, the apparent dissociation constant for AMP increased
      more than 4-fold as compared to the value for the wild-type enzyme. The
      replacement of Glu-192, which forms interactions across the C1:C4 dimer-dimer
      interface, with Ala and Gln lowered kcat from 21 s-1 for wild-type enzyme to 15 s
      1 and 13 s-1, respectively, for the mutant enzymes, while their respective Km
      values were not changed. However, these replacements did have dramatic effects on
      AMP inhibition; first, cooperative AMP inhibition was lost; second, the AMP
      inhibition was biphasic, which can be interpreted as due to AMP binding to two
      classes of binding sites. The high affinity class of sites corresponds to the
      regulatory sites, while the low affinity class of sites may be the active sites.
      The results reported here, combined with the structural and kinetic results from
      the Lys-42 --> Ala enzyme, strongly suggest that the C1:C4 dimer-dimer interface,
      rather than the C1:C2 monomer-monomer interface, is critical for the propagation
      of the allosteric signal between the AMP sites on different subunits; in
      addition, cooperative AMP inhibition is essential for the enzyme to be fully
      inhibited by the binding of AMP to the allosteric site.

PMID- 9030573
TI  - Regulation of the soxRS oxidative stress regulon. Reversible oxidation of the Fe
      S centers of SoxR in vivo.
AB  - SoxR protein, a transcriptional activator of the soxRS (superoxide response)
      regulon of Escherichia coli, contains autooxidizable [2Fe-2S] centers that are
      presumed to serve as redox sensors. In vitro transcription experiments previously
      demonstrated that only the oxidized form is active. Reduced SoxR was detected in
      overproducing strains by EPR spectroscopy of suspensions of intact cells.
      Oxidized Fe-S centers were determined by lysing the cells and treating them with
      the reducing agent sodium dithionite prior to EPR measurements. In uninduced
      cells, 90% of the SoxR was in the reduced form. Treatment with the redox cycling
      agents phenazine methosulfate or plumbagin was accompanied by reversible
      oxidation of the Fe-S centers. Mutant SoxR derivatives that were constitutively
      activated existed constitutively in an oxidized state. The results indicate the
      presence of a cellular pathway for countering the autooxidation of SoxR and
      confirm the hypothesis that induction of the regulon is mediated by a shift in
      the redox equilibrium of SoxR rather than by assembly of its Fe-S clusters.

PMID- 9030574
TI  - A molecular basis for different interactions of marine toxins with protein
      phosphatase-1. Molecular models for bound motuporin, microcystins, okadaic acid,
      and calyculin A.
AB  - The hepatotoxic cyclic heptapeptide microcystins and cyclic pentapeptide
      nodularins are powerful liver tumor promoters and potent inhibitors of the
      catalytic subunits of protein phosphatase-1 and -2A (PP-1c and PP-2Ac). In marked
      contrast to microcystins, which interact covalently with PP-1 and PP-2A, the
      nodularins do not bind covalently to PP-1 and PP-2A and may additionally possess
      unique carcinogenic properties. The conformation of microcystin-LR has been
      determined in solution and bound to PP-1c. We show here that the free NMR
      solution structures of two distinct microcystin structural congeners (microcystin
      LR and -LL) are remarkably similar to the bound crystal structure of microcystin
      LR. We have exploited this finding by using Metropolis Monte Carlo modeling to
      dock the solution structures of microcystin-LL and the marine toxin motuporin
      (nodularin-V) onto the crystal structure of PP-1c. Both of these toxins occupy a
      position similar to that of microcystin-LR when bound to PP-1c. However, although
      there are relatively minor differences in the structural orientation of
      microcystin-LL compared with microcystin-LR, there is a striking difference in
      the position of the N-methyldehydrobutyrine residue in motuporin relative to the
      comparable N-methyldehydroalanine residue in microcystin-LR. We propose that this
      difference in orientation provides a molecular explanation for why nodularins are
      incapable of forming a covalent linkage with PP-1c. Furthermore, the predicted
      position of N-methyldehydrobutyrine in motuporin is at the surface of the PP-1c
      toxin complex, which may thus facilitate chemical interaction with a further
      macromolecule(s) possibly relating to its carcinogenic properties. PP-1c and PP
      2Ac are also targets for other marine toxins such as okadaic acid and calyculin
      A. It was therefore of interest to use Metropolis Monte Carlo modeling to dock
      the known free crystal structures of okadaic acid and calyculin A to the crystal
      structure of PP-1c. These experiments predict that both okadaic acid and
      calyculin A are strikingly similar to microcystins and motuporin in their
      tertiary structure and relative PP-1c binding position.

PMID- 9030575
TI  - Isolation and characterization of the 5'-upstream region of the human N-type
      calcium channel alpha1B subunit gene. Chromosomal localization and promoter
      analysis.
AB  - omega-Conotoxin-sensitive N-type Ca2+ channels, unlike dihydropyridine-sensitive
      L-type channels, are exclusively expressed in nervous tissues. To understand the
      molecular basis for neuron-specific expression of the N-type channel, we have
      isolated genomic clones encoding the human alpha1B subunit gene, localized to the
      long arm of chromosome 9 (9q34) by fluorescence in situ hybridization, and
      characterized its 5'-upstream region. The proximal promoter of the alpha1B
      subunit gene lacks a typical TATA box, is highly GC-rich, and contains several
      sequences for transcription factor binding. Primer extension experiments revealed
      the presence of two transcription start sites. In vitro transfection study of the
      alpha1B subunit-luciferase fusion gene showed that the 4.0-kb 5'-flanking region
      of the alpha1B gene functions as an efficient promoter in neuronal cells but not
      in glioma or nonneuronal cells, consistent with the patterns of the endogenous
      alpha1B gene expression in these cells. Deletion analysis of alpha1B subunit
      luciferase fusion gene constructs further revealed the presence of several cis
      acting regulatory elements, including a potential repressor located in the distal
      upstream region (-3992 to -1788) that may be important for the neuron-specific
      expression of the N-type Ca2+ channel alpha1B subunit gene.

PMID- 9030576
TI  - Model peptide studies demonstrate that amphipathic secondary structures can be
      recognized by the chaperonin GroEL (cpn60).
AB  - The molecular chaperone cpn60 binds many unfolded proteins and facilitates their
      proper folding. Synthetic peptides have been used to probe the question of how
      cpn60 might recognize such a diverse set of unfolded proteins. Three hybrid
      peptides were synthesized encompassing portions of the bee venom peptide, apamin,
      and the sequence KWLAESVRAGK from an amphipathic helix in the NH2-terminal region
      of bovine rhodanese. Two disulfides connecting cysteine residues hold the
      peptides in stable helical conformations with unobstructed faces oriented away
      from the disulfides. Peptides were designed to present either a hydrophobic or
      hydrophilic face of the amphipathic helix that is similar to the one near the
      amino terminus of rhodanese. Aggregation of these peptides was detected by
      measuring 1,1'-bis(4-anilino)napthalene-5,5'-disulfonic acid (bisANS)
      fluorescence at increasing peptide concentrations, and aggregation was not
      apparent below 2 microM. Thus, all experiments with the peptides were performed
      at a concentration of 1 microM. Reducing agents cause these helical peptides to
      form random coils. Fluorescence anisotropy measurements of fluorescein-labeled
      peptide with the exposed hydrophobic face yielded a Kd = approximately 106 microM
      for binding to cpn60, whereas there was no detectable binding of the reduced
      form. The peptide with the exposed hydrophilic face did not bind to cpn60 in
      either the oxidized or reduced states. Fluorescence experiments utilizing bisANS
      as a probe showed that binding of the helical hydrophobic peptide could induce
      the exposure of hydrophobic surfaces on cpn60, whereas the same peptide in its
      random coil form had no effect. Thus, binding to cpn60 is favored by a secondary
      structure that organizes and exposes a hydrophobic surface, a feature found in
      amphipathic helices. Further, the binding of a hydrophobic surface to cpn60 can
      induce further exposure of complementary surfaces on cpn60 complexes, thus
      amplifying interactions available for target proteins.

PMID- 9030577
TI  - The use of fluorescent probes to characterize conformational changes in the
      interaction between vitronectin and plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type
      plasminogen activator and urokinase, is known to convert readily to a latent form
      by insertion of the reactive center loop into a central beta-sheet. Interaction
      with vitronectin stabilizes PAI-1 and decreases the rate of conversion to the
      latent form, but conformational effects of vitronectin on the reactive center
      loop of PAI-1 have not been documented. Mutant forms of PAI-1 were designed with
      a cysteine substitution at either position P1' or P9 of the reactive center loop.
      Labeling of the unique cysteine with a sulfhydryl-reactive fluorophore provides a
      probe that is sensitive to vitronectin binding. Results indicate that the
      scissile P1-P1' bond of PAI-1 is more solvent exposed upon interaction with
      vitronectin, whereas the N-terminal portion of the reactive loop does not
      experience a significant change in its environment. These results were
      complemented by labeling vitronectin with an arginine-specific coumarin probe
      which compromises heparin binding but does not interfere with PAI-1 binding to
      the protein. Dissociation constants of approximately 100 nM are calculated for
      the vitronectin/PAI-1 interaction from titrations using both fluorescent probes.
      Furthermore, experiments in which PAI-1 failed to compete with heparin for
      binding to vitronectin argue for separate binding sites for the two ligands on
      vitronectin.

PMID- 9030578
TI  - Induction of apoptosis and CPP32 expression by thyroid hormone in a myoblastic
      cell line derived from tadpole tail.
AB  - During amphibian metamorphosis, the tail and gills that are useful in aquatic
      life but inappropriate for terrestrial activity are induced to degenerate
      completely in several days by endogenous thyroid hormone (TH). The dramatic
      resorption of the tadpole tail has attracted a good deal of attention as an
      experimental system of cell death, but the mechanism has not been well
      characterized. To facilitate in vitro analysis, we have established a myoblast
      cell line (XLT-15) derived from the Xenopus laevis tadpole tail. This cultured
      cell line died in response to TH and exhibited positive TUNEL reaction and
      internucleosomal DNA cleavage. Simultaneously, expression of the Xenopus
      CPP32/apopain/Yama gene was up-regulated by TH in the cell line as it is in
      regressing tadpole tail, whereas interleukin-1beta-converting enzyme (ICE) mRNA
      is around 1 copy/cell in tail and undetectable in XLT-15 cells. A
      CPP32/apopain/Yama inhibitor (acetyl-Asp-Glu-Val-Asp-aldehyde) prevented TH
      induced apoptosis of XLT-15 cells, but an ICE inhibitor (acetyl-Tyr-Val-Ala-Asp
      aldehyde) did not. These results suggested that an increase of CPP32/apopain/Yama
      gene expression is involved in TH-dependent apoptosis of XLT-15 and tadpole tail
      resorption during metamorphosis.

PMID- 9030579
TI  - Transcriptional activation by peroxisome proliferator-activated receptor gamma is
      inhibited by phosphorylation at a consensus mitogen-activated protein kinase
      site.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      regulates transcription in response to prostanoid and thiazolidinedione ligands
      and promotes adipocyte differentiation. The amino-terminal A/B domain of this
      receptor contains a consensus mitogen-activated protein kinase site in a region
      common to PPARgamma1 and -gamma2 isoforms. The A/B domain of human PPARgamma1 was
      phosphorylated in vivo, and this was abolished either by mutation of serine 84 to
      alanine (S84A) or coexpression of a phosphoprotein phosphatase. In vitro, this
      domain was phosphorylated by ERK2 and JNK, and this was markedly reduced in the
      S84A mutant. A wild type Gal4-PPARgamma(A/B) chimera exhibited weak constitutive
      transcriptional activity. Remarkably, this was significantly enhanced in the S84A
      mutant fusion. Ligand-dependent activation by full-length mouse PPARgamma2 was
      also augmented by mutation of the homologous serine in the A/B domain to alanine.
      The nonphosphorylatable form of PPARgamma was also more adipogenic. Thus,
      phosphorylation of a mitogen-activated protein kinase site in the A/B region of
      PPARgamma inhibits both ligand-independent and ligand-dependent transactivation
      functions. This observation provides a potential mechanism whereby
      transcriptional activation by PPARgamma may be modulated by growth factor or
      cytokine-stimulated signal transduction pathways involved in adipogenesis.

PMID- 9030580
TI  - The role of receptor dimerization domain residues in growth hormone signaling.
AB  - While there is a considerable amount of evidence that signal transduction by the
      growth hormone (GH) receptor requires receptor homodimerization, there has been
      no systematic study of the role of receptor dimerization domain residues in this
      process. In conjunction with the distances derived from the crystal structure of
      the hGH-hGH receptor (extracellular domain) complex, we have used a luciferase
      based c-fos promoter reporter assay in transiently transfected Chinese hamster
      ovary (CHO) cells, and stable receptor expressing CHO cell populations to define
      the dimerization domain residues needed for effective signaling. In addition to
      alanine substitution, we have used both aspartate and lysine substitutions to
      allow us to provide evidence for proximity relations through charge
      complementation. Introduced cysteine substitutions were also used, but unlike the
      erythropoietin receptor, these were unable to generate constitutively active
      receptor. We conclude that serine 145, histidine 150, aspartate 152, tyrosine
      200, and serine 201, but not leucine 146 or threonine 147 are required for
      effective signal transduction through the dimerization domain. This information
      may be valuable in designing small molecule antagonists of GH and other cytokines
      that block dimerization by binding to the dimerization domain.

PMID- 9030581
TI  - Molecular cloning and functional characterization of a novel mitogen-activated
      protein kinase phosphatase, MKP-4.
AB  - Extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase/stress
      activated protein kinase (JNK/SAPK), and p38/RK/CSBP (p38) mitogen-activated
      protein (MAP) kinases are target enzymes activated by a wide range of cell
      surface stimuli. Recently, a distinct class of dual specificity phosphatase has
      been shown to reverse activation of MAP kinases by dephosphorylating critical
      tyrosine and threonine residues. By searching the expressed sequence tag data
      base (dbEST) for homologues of known dual specificity phosphatases, we identified
      a novel partial human sequence for which we isolated a full-length cDNA (termed
      MKP-4). The deduced amino acid sequence of MKP-4 is most similar to MKP-X/PYST2
      (61% identity) and MKP-3/PYST1 (57% identity), includes two N-terminal CH2
      domains homologous to the cell cycle regulator Cdc25 phosphatase, and contains
      the extended active site sequence motif VXVHCXAGXSRSXTX3AYLM (where X is any
      amino acid) conserved in dual specificity phosphatases. MKP-4 produced in
      Escherichia coli catalyzes vanadate-sensitive breakdown of p-nitrophenyl
      phosphate as well as in vitro inactivation of purified ERK2. When expressed in
      COS-7 cells, MKP-4 blocks activation of MAP kinases with the selectivity ERK >
      p38 = JNK/SAPK. This cellular specificity is similar to MKP-3/PYST1, although
      distinct from hVH-5/M3-6 (JNK/SAPK = p38 >>> ERK). Northern analysis reveals a
      highly restricted tissue distribution with a single MKP-4 mRNA species of
      approximately 2.5 kilobases detected only in placenta, kidney, and embryonic
      liver. Immunocytochemical analysis showed MKP-4 to be present within cytosol
      although punctate nuclear staining co-localizing with promyelocytic protein was
      also observed in a subpopulation (10-20%) of cells. Chromosomal localization by
      analysis of DNAs from human/rodent somatic cell hybrids and a panel of radiation
      hybrids assign the human gene for MKP-4 to Xq28. The identification and
      characterization of MKP-4 highlights the emergence of an expanding family of
      structurally homologous dual specificity phosphatases possessing distinct MAP
      kinase specificity and subcellular localization as well as diverse patterns of
      tissue expression.

PMID- 9030582
TI  - Interaction of endoplasmic reticulum chaperone GRP94 with peptide substrates is
      adenine nucleotide-independent.
AB  - GRP94, the endoplasmic reticulum paralog of hsp90, has recently been identified
      as a peptide and adenine nucleotide-binding protein. To determine if adenine
      nucleotides directly contribute to the regulation of GRP94 peptide binding
      activity, an in vitro peptide binding assay was developed. Using purified GRP94,
      we observed specific, saturable, temperature-sensitive binding of the peptide
      VSV8, a known in vivo ligand. ATP was without effect on VSV8 binding to GRP94,
      whether present during or subsequent to peptide binding. To evaluate the
      interaction of GRP94 with adenine nucleotides, the ATP binding and hydrolysis
      activities were directly assayed. Only negligible binding of ATP to GRP94 was
      observed. In addition, analysis of the GRP94 adenine nucleotide content indicated
      that GRP94 did not copurify with bound adenine nucleotides. GRP94 preparations
      exhibited low ATPase and apparent autophosphorylation activities. Further
      purification, combined with inhibitor studies, indicated that both activities
      were the result of trace contamination (<0.1%) with casein kinase II. On the
      basis of these data, we propose that the peptide binding activity of GRP94 is
      adenine nucleotide-independent and that ATP binding and hydrolysis are not
      inherent properties of GRP94.

PMID- 9030583
TI  - Characterization of protein kinase A and protein kinase C phosphorylation of the
      N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific
      antibodies.
AB  - Modulation of N-methyl-D-aspartate receptors in the brain by protein
      phosphorylation may play a central role in the regulation of synaptic plasticity.
      To examine the phosphorylation of the NR1 subunit of N-methyl-D-aspartate
      receptors in situ, we have generated several polyclonal antibodies that recognize
      the NR1 subunit only when specific serine residues are phosphorylated. Using
      these antibodies, we demonstrate that protein kinase C (PKC) phosphorylates
      serine residues 890 and 896 and cAMP-dependent protein kinase (PKA)
      phosphorylates serine residue 897 of the NR1 subunit. Activation of PKC and PKA
      together lead to the simultaneous phosphorylation of neighboring serine residues
      896 and 897. Phosphorylation of serine 890 by PKC results in the dispersion of
      surface-associated clusters of the NR1 subunit expressed in fibroblasts, while
      phosphorylation of serine 896 and 897 has no effect on the subcellular
      distribution of NR1. The PKC-induced redistribution of the NR1 subunit in cells
      occurs within minutes of serine 890 phosphorylation and reverses upon
      dephosphorylation. These results demonstrate that PKA and PKC phosphorylate
      distinct residues within a small region of the NR1 subunit and differentially
      affect the subcellular distribution of the NR1 subunit.

PMID- 9030584
TI  - Identification and characterization of a fibroblast growth factor (FGF) binding
      domain in the cysteine-rich FGF receptor.
AB  - Three distinct transmembrane glycoproteins bind fibroblast growth factor (FGF)
      family members. These include heparan sulfate proteoglycans, the tyrosine kinase
      containing FGF receptors (FGFRs), and a cysteine-rich FGF receptor (CFR). The
      four FGFRs are thought to mediate FGF-signaling events but require the
      participation of the heparan sulfate proteoglycans to bind FGFs and transduce
      intracellular signals. However, a number of groups have proposed that FGF action
      requires events independent of FGFR activation. CFR, a high affinity FGF-binding
      protein, was first isolated from chicken embryos. To better understand the
      interactions between CFR and FGFs, we have constructed a series of CFR deletion
      mutants and CFR fragments. Analysis of these has identified a approximately 200
      amino acid domain that constitutes a CFR FGF binding site. A CFR fragment of 450
      residues, CFR290-740, binds FGF-2 with an affinity indistinguishable from the
      full-length molecule, whereas smaller fragments display greatly reduced FGF
      binding. Although CFR binds heparin with high affinity, an analysis of the
      heparin-CFR interaction failed to identify a linear sequence containing a heparin
      binding site. Two types of FGF binding sites were identified: an ionic strength
      and heparin-independent site that represents FGF binding to CFR290-740 and an
      additional FGF binding site that is heparan sulfate-dependent and sensitive to
      high ionic strength. This latter site is likely to bind FGF indirectly via
      heparan sulfate binding to CFR. FGF-2 peptides that encompass a sequence
      implicated in FGF-2 binding to FGFRs also block FGF-2 binding to CFR. Our data
      suggest that binding of FGFs to CFR and FGFRs is mutually exclusive, since the
      CFR FGF binding site does not require heparan sulfate, and similar regions on FGF
      2 interact with both FGFRs and CFR.

PMID- 9030585
TI  - Targeting of SCG10 to the area of the Golgi complex is mediated by its NH2
      terminal region.
AB  - SCG10 is a neuronal growth-associated protein that is concentrated in the growth
      cones of developing neurons. SCG10 shows a high degree of sequence homology to
      the ubiquitous phosphoprotein stathmin, which has been recently identified as a
      factor that destabilizes microtubules by increasing their catastrophe rate.
      Whereas stathmin is a soluble cytosolic protein, SCG10 is membrane-associated,
      indicating that the protein acts in a distinct subcellular compartment.
      Identifying the precise intracellular distribution of SCG10 as well as the
      mechanisms responsible for its specific targeting will contribute to elucidating
      its function. The main structural feature distinguishing the two proteins is that
      SCG10 contains an NH2-terminal extension of 34 amino acids. In this study, we
      have examined the intracellular distribution of SCG10 in PC12 cells and in
      transfected COS-7 cells and the role of the NH2-terminal domain in membrane
      binding and intracellular targeting. SCG10 was found to be localized to the Golgi
      complex region. We show that the NH2-terminal region (residues 1-34) was
      necessary for membrane targeting and Golgi localization. Fusion proteins
      consisting of the NH2-terminal 34 amino acids of SCG10 and the related protein
      stathmin or the unrelated protein, beta-galactosidase, accumulated in the Golgi,
      demonstrating that this sequence was sufficient for Golgi localization.
      Biosynthetic labeling of transfected COS-7 cells with [3H]palmitic acid revealed
      that two cysteine residues contained within the NH2-terminal domain were sites of
      palmitoylation.

PMID- 9030586
TI  - Protein kinase A (PKA)- and protein kinase C-phosphorylated glia maturation
      factor promotes the catalytic activity of PKA.
AB  - We observed previously that glia maturation factor (GMF), a 17-kDa brain protein,
      is rapidly phosphorylated in astrocytes following stimulation by phorbol ester,
      and that protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of
      extracellular signal-regulated kinase (ERK) and enhancer of p38; both are
      subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a
      bifunctional regulator of the MAP kinase cascades. In the current report, we
      present evidence that PKA-phosphorylated GMF also promotes (11-fold) the
      catalytic activity of PKA itself, resulting in a positive feedback loop.
      Furthermore, GMF phosphorylated by protein kinase C (PKC), but not by casein
      kinase II or p90 ribosomal S6 kinase, also activates PKA (7-fold). It appears
      that the mutual augmentation of GMF and PKA, and the stimulating effect of PKC,
      both serve to maximize the influence of PKA on the regulation of MAP kinase
      cascades by GMF. Using synthetic peptide fragments containing putative
      phosphorylation sites of GMF, we demonstrate that PKA is capable of
      phosphorylating threonine 26 and serine 82, whereas PKC, p90 ribosomal S6 kinase,
      and casein kinase II, can phosphorylate serine 71, threonine 26, and serine 52,
      respectively. The generation of various phospho-isoforms of GMF may explain its
      modulation of signal transduction at multiple locations.

PMID- 9030587
TI  - Hepatocyte growth factor promotes motor neuron survival and synergizes with
      ciliary neurotrophic factor.
AB  - Hepatocyte growth factor (HGF) has been shown to function as a potent mitogen for
      a variety of cells, transducing its signal through the c-met tyrosine kinase
      receptor. Ciliary neurotrophic factor (CNTF) is a cytokine that has been shown to
      promote survival of motor neurons. We show here that c-met mRNA is present in the
      embryonic rat spinal cord. Peak expression of c-met (at E14) coincides with the
      period of naturally occurring cell death in motor neurons, suggesting a possible
      role of HGF in the regulation of this process. Utilizing a neuron-enriched
      culture system, we established that HGF, like CNTF, stimulates choline
      acetyltransferase (CAT) activity in motor neurons. When co-administered to motor
      neuron cultures, saturating concentrations of HGF and CNTF produced a synergistic
      increase in CAT levels. We show that this synergy reflects enhanced motor neuron
      survival. Exposure of motor neuron cultures to the cytostatic agent vincristine
      markedly decreased CAT levels; co-treatment with HGF and CNTF (but not either
      factor alone) restored CAT activity to control levels. Our findings indicate that
      HGF is a survival factor for motor neurons, that it acts synergistically with
      CNTF, and that HGF and CNTF can together be neuroprotective in the face of
      vincristine toxicity.

PMID- 9030588
TI  - Conversion from archaeal geranylgeranyl diphosphate synthase to farnesyl
      diphosphate synthase. Two amino acids before the first aspartate-rich motif
      solely determine eukaryotic farnesyl diphosphate synthase activity.
AB  - Farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are precursors
      for a variety of important natural products, such as sterols, carotenoids, and
      prenyl quinones. Although FPP synthase and GGPP synthase catalyze similar
      consecutive condensations of isopentenyl diphosphate with allylic diphosphates
      and have several homologous regions in their amino acid sequences, nothing is
      known about how these enzymes form the specific products. To locate the region
      that causes the difference of final products between GGPP synthase and FPP
      synthase, we constructed six mutated archaeal GGPP synthases whose regions around
      the first aspartate-rich motif were replaced with the corresponding regions of
      FPP synthases from human, rat, Arabidopsis thaliana, Saccharomyces cerevisiae,
      Escherichia coli, Bacillus stearothermophilus, and from some other related
      mutated enzymes. From the analysis of these mutated enzymes, we revealed that the
      region around the first aspartate-rich motif is essential for the product
      specificity of all FPP synthases and that the mechanism of the chain termination
      in eukaryotic FPP synthases (type I) is different from those of prokaryotic FPP
      synthases (type II). In FPP synthases of type I, two amino acids situated at the
      fourth and the fifth positions before the motif solely determine their product
      chain length, while the product specificity of the type II enzymes is determined
      by one aromatic amino acid at the fifth position before the motif, two amino
      acids inserted in the motif, and other modifications. These data indicate that
      FPP synthases have evolved from the progenitor corresponding to the archaeal GGPP
      synthase in two ways.

PMID- 9030589
TI  - Biosynthesis, processing, and intracellular transport of GM2 activator protein in
      human epidermal keratinocytes. The lysosomal targeting of the GM2 activator is
      independent of a mannose-6-phosphate signal.
AB  - The processing, intracellular transport, and endocytosis of the GM2 activator
      protein (GM2AP), an essential cofactor of beta-hexosaminidase A for the
      degradation of ganglioside GM2, was investigated in human epidermal
      keratinocytes. The GM2AP precursor is synthesized as an 18-kDa peptide, which is
      singly glycosylated, resulting in 22-kDa high mannose and 24-27-kDa complex
      glycoforms. A small portion of the 22-kDa form bears phosphomannosyl residues.
      About 30% of the GM2AP precursor is secreted during 12 h after synthesis,
      consisting almost exclusively of complex glycoforms. In a post-Golgi compartment,
      the intracellular remainder is converted to a 20-kDa mature form within 24 h,
      bearing a heavily trimmed N-glycan on a 17-kDa backbone. Interestingly, even
      nonglycosylated GM2AP is delivered to the lysosome, as shown by tunicamycin
      treatment and subcellular fractionation. Also, its endocytosis is independent of
      carbohydrate-linked signals and is even more effective for nonglycosylated GM2AP.
      We conclude that a mannose-6-phosphate-independent pathway for the lysosomal
      delivery of GM2AP exists in cultured human keratinocytes.

PMID- 9030590
TI  - Nuclear ADP-ribosylation factor (ARF)- and oleate-dependent phospholipase D (PLD)
      in rat liver cells. Increases of ARF-dependent PLD activity in regenerating liver
      cells.
AB  - Two forms of phospholipase D (PLD) have been found to be present in nuclei
      isolated from rat hepatocytes by measuring phosphatidylbutanol produced from
      exogenous radiolabeled phosphatidylcholine in the presence of butanol. In nuclear
      lysates from either rat liver or ascites hepatoma AH 7974 cells, the PLD activity
      was markedly stimulated by a recombinant ADP-ribosylation factor (rARF) in the
      presence of the guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) and
      phosphatidylinositol 4, 5-bisphosphate. ATP and phorbol-12-myristate 13-acetate
      had no synergistic effect on this PLD activity. On the other hand, the nuclear
      PLD was stimulated by unsaturated fatty acids, especially by oleic acid. The ARF
      dependent nuclear PLD activity was increased in the S-phase of the regenerating
      rat liver after partial hepatectomy and also was much higher in AH 7974 cells
      than in the resting rat liver. In contrast, the levels of the oleate-dependent
      PLD activity remained constant throughout the cell cycle in liver regeneration.
      The intranuclear levels of the stimulating proteins of the nuclear PLD activity,
      e.g. ARF, RhoA, and protein kinase Cdelta increased in the S-phase of the
      regenerating liver. These results suggested that the nuclear ARF-dependent PLD
      activity may be associated with cell proliferation.

PMID- 9030591
TI  - Tyrosine phosphorylation of paxillin and focal adhesion kinase during insulin
      like growth factor-I-stimulated lamellipodial advance.
AB  - In the current studies, we examined whether focal adhesion kinase (FAK) and
      paxillin play a role in insulin-like growth factor-I (IGF-I)-stimulated
      morphological changes in neuronal cells. In SH-SY5Y human neuroblastoma cells, 10
      nM IGF-I enhanced the extension of lamellipodia within 30 min. Scanning electron
      microscopy and staining with rhodamine-phalloidin showed that these lamellipodia
      displayed ruffles, filopodia, and a distinct meshwork of actin filaments.
      Immunofluorescent staining identified focal concentrations of FAK, paxillin, and
      phosphotyrosine within the lamellipodia. Immunoprecipitation experiments revealed
      that FAK and paxillin are tyrosine-phosphorylated during IGF-I-stimulated
      lamellipodial extension. Maximal phosphorylation of FAK and paxillin was observed
      15-30 min after the addition of 10 nM IGF-I, whereas maximal IGF-I receptor
      phosphorylation occurred within 5 min. FAK, paxillin, and IGF-I receptor tyrosine
      phosphorylation had similar concentration-response curves and were inhibited by
      the receptor blocking antibody alphaIR-3. These results indicate that FAK and
      paxillin are tyrosine-phosphorylated during IGF-I-stimulated lamellipodial
      advance and suggest that the tyrosine phosphorylation of these two proteins helps
      mediate IGF-I-stimulated cell and growth cone motility. These responses contrast
      directly with recent reports showing insulin-stimulated dephosphorylation of FAK
      and paxillin.

PMID- 9030592
TI  - Structural and functional characterization of the human perlecan gene promoter.
      Transcriptional activation by transforming growth factor-beta via a nuclear
      factor 1-binding element.
AB  - Perlecan, a modular heparan sulfate proteoglycan of basement membranes and cell
      surfaces, plays a crucial role in regulating the assembly of extracellular
      matrices and the binding of nutrients and growth factors to target cells. To
      achieve a molecular understanding of perlecan gene regulation, we isolated the 5'
      flanking region and investigated its functional promoter activity and its
      response to cytokines. Transient cell transfection assays, using plasmid
      constructs harboring the perlecan promoter linked to the chloramphenicol
      acetyltransferase reporter gene, demonstrated that the largest approximately 2.5
      kilobase construct contained maximal promoter activity. This promoter region was
      functionally active in a variety of cells of diverse histogenetic origin, thus
      corroborating the widespread expression of this gene product. Stepwise 5'
      deletion analyses demonstrated that the -461-base pair (bp) proximal promoter
      retained approximately 90% of the total activity, and internal deletions
      confirmed that the most proximal sequence was essential for proper promoter
      activity. Nanomolar amounts of transforming growth factor-beta induced 2-3-fold
      perlecan mRNA and protein core levels in normal human skin fibroblasts, and this
      induction was transcriptionally regulated; in contrast, tumor necrosis factor
      alpha had no effect and was incapable of counteracting the effects of TGF-beta.
      Using additional 5' deletions and DNase footprinting analyses, we mapped the TGF
      beta responsive region to a sequence of 177 bp contained between -461 and -285.
      This region harbored a 14-bp element similar to a TGF-beta-responsive element
      present in the promoters of collagen alpha1(I), alpha2(I), elastin, and growth
      hormone. Electrophoretic mobility shift assays and mutational analyses
      demonstrated that the perlecan TGF-beta-responsive element bound specifically to
      TGF-beta-inducible nuclear proteins with high affinity for NF-1 member(s) of
      transcription factors.

PMID- 9030593
TI  - Different domains cooperate to target the human ribosomal L7a protein to the
      nucleus and to the nucleoli.
AB  - The human ribosomal protein L7a is a component of the major ribosomal subunit. We
      transiently expressed in HeLa cells L7a-beta-galactosidase fusion proteins and
      studied their subcellular localization by indirect immunofluorescence staining
      with anti-beta-galactosidase antibodies. We have identified three distinct
      domains responsible for the nuclear targeting of the protein: domain I, amino
      acids 23-51; domain II, amino acids 52-100; domain III, amino acids 101-220, each
      of which contains at least one nuclear localization signal (NLS). Through
      subcellular localization analysis of deletion mutants of L7a-beta-galactosidase
      chimeras, we demonstrate that domain II plays a special role because it is
      necessary, although not sufficient, to target the chimeric beta-galactosidase to
      the nucleoli. In fact, we demonstrate that the nucleolar targeting process
      requires the presence of domain II plus an additional basic domain that can be
      represented by an NLS or a basic stretch of amino acids without NLS activity.
      Thus, when multiple NLS are present, each NLS exerts distinct functions. Domain
      II drives nucleolar accumulation of a reporter protein with the cooperative
      action of a short basic amino acid sequence, suggesting a mechanism requiring
      protein-protein or protein-nucleic acid interactions.

PMID- 9030594
TI  - Identification of human cadherin-14, a novel neurally specific type II cadherin,
      by protein interaction cloning.
AB  - Cadherins, a family of Ca2+-dependent cell-cell adhesion molecules, mediate
      neural cell-cell interactions and may play important roles in neural development.
      By searching for molecules that interact with beta-catenin, a cytoplasmic
      regulator of cadherins, we have identified a new member of the cadherin family,
      which we named human cadherin-14. Cadherin-14 had high amino acid sequence
      homology with the type II subgroup of cadherins and was broadly expressed in the
      central nervous system. Cadherin-14 is a novel neurally specific cell-cell
      adhesion molecule and may regulate neural morphogenesis.

PMID- 9030595
TI  - Basolateral localization and transcytosis of gonadotropin and thyrotropin
      receptors expressed in Madin-Darby canine kidney cells.
AB  - The thyrotropin (TSH) and follicle-stimulating hormone (FSH) receptors are
      present mainly on the basolateral cell surface in the thyroid gland and in
      Sertoli cells, whereas in ovarian and in testicular cells, the luteinizing
      hormone (LH) receptors are distributed throughout the cell surface. When
      expressed in Madin-Darby canine kidney (MDCK) cells, all three receptors
      accumulated at the basolateral cell surface showing that they carry the
      corresponding targeting signals. The receptors were directly delivered to the
      basolateral surface of the MDCK cells. A minor fraction of the gonadotropin
      receptors but not of TSH receptors was secondarily targeted to the apical surface
      through transcytosis. The mechanisms of basolateral targeting and transcytosis
      were analyzed using the FSH receptor as a model. Both were insensitive to
      brefeldin A and pertussis toxin. Gs activation by AlF4- and cholera toxin
      provoked a marked enhancement of FSH receptor transcytosis. The population of Gs
      proteins involved in this mechanism was different from that involved in signal
      transduction since neither FSH nor forskolin mimicked the effects of AlF4- and
      cholera toxin. Gs activation provoked a similar effect on LH receptor
      distribution in MDCK cells, whereas it did not modify the compartmentalization of
      the TSH receptor. Hormone-specific transcytosis was observed in MDCK cells
      expressing the gonadotropin (FSH and LH) receptors and was increased after
      cholera toxin administration.

PMID- 9030596
TI  - Identification of two conformationally sensitive cysteine residues at the
      extracellular surface of the Na,K-ATPase alpha-subunit.
AB  - Na,K-ATPase in right-side-out oriented vesicles was stabilized in different
      conformations, and the location of intramembrane Cys residues of the alpha
      subunit was assessed with membrane-permeable and membrane-impermeable Cys
      directed reagents. In the presence of Mg2+ and Pi, Cys964 was the most accessible
      for both membrane-impermeable 4-acetamido-4'-maleimidylstilbene-2, 2'disulfonic
      acid (or stilbene disulfonate maleimide, SDSM) and membrane-permeable 7
      diethylamino-3-(4'-maleimidyl)-4-methylcoumarin (CPM). In the presence of K+,
      Cys964 was modified only by hydrophobic CPM, indicating that the environment
      around Cys964 was different in these two conformations. Cys964 seems to mark the
      extracellular border of transmembrane segment M9. Cys911 in transmembrane segment
      M8 showed similar behavior; however, it was not so readily modified. Complete
      modification of Cys964 and Cys911 causes only partial (about 50%) inactivation of
      both ATPase activity and Rb+ (or K+) occlusion, indicating that the effect on
      cation occlusion is indirect and not within the occlusion cavity. The ATP binding
      capacity remains unaltered by the modifications. Treatment of the K+-stabilized
      post-tryptic preparation of purified Na, K-ATPase revealed labeling of several
      cysteines by CPM, none of which were labeled with SDSM. Removal of K+ ions from
      the preparation, which we have previously shown is accompanied by release of the
      M5M6 hairpin to the supernatant (), causes changes in the organization of the C
      terminal 21-kDa fragment. In particular Cys983 in M10 became labeled by both CPM
      and SDSM, pointing to a tight association between the C terminus and the M5M6
      hairpin of the alpha-subunit.

PMID- 9030597
TI  - Functional characterization of a distinct ryanodine receptor mutation in human
      malignant hyperthermia-susceptible muscle.
AB  - Malignant hyperthermia is an inherited autosomal disorder of skeletal muscle in
      which certain volatile anesthetics and depolarizing muscle relaxants trigger an
      abnormally high release of Ca2+ from the intracellular Ca2+ store, the
      sarcoplasmic reticulum. In about 50% of cases, malignant hyperthermia
      susceptibility is linked to the gene encoding the skeletal muscle ryanodine
      receptor/Ca2+ release channel (RYR1). To date, eight point mutations have been
      identified in human RYR1. Although these mutations are thought to lead to an
      increased caffeine and halothane sensitivity in the contractile response of
      skeletal muscle, their functional consequences have not been investigated on the
      molecular level. In the present study, we provide the first functional
      characterization of a point mutation located in the central part of RYR1, Gly2434
      --> Arg. Using high affinity [3H]ryanodine binding as the experimental approach,
      we show that this mutation enhances the sensitivity of RYR1 to activating
      concentrations of Ca2+ and to the exogenous and diagnostically used ligands
      caffeine and 4-chloro-m-cresol. In parallel, the sensitivity to inhibiting
      concentrations of Ca2+ and calmodulin was reduced, transferring the mutant Ca2+
      release channel into a hyperexcitable state.

PMID- 9030598
TI  - Distinct functions of Gq and G11 proteins in coupling alpha1-adrenoreceptors to
      Ca2+ release and Ca2+ entry in rat portal vein myocytes.
AB  - In this study, we identified the subunit composition of Gq and G11 proteins
      coupling alpha1-adrenoreceptors to increase in cytoplasmic Ca2+ concentration
      ([Ca2+]i) in rat portal vein myocytes maintained in short-term primary culture.
      We used intranuclear antisense oligonucleotide injection to inhibit selectively
      the expression of subunits of G protein. Increases in [Ca2+]i were measured in
      response to activation of alpha1-adrenoreceptors, angiotensin AT1 receptors, and
      caffeine. Antisense oligonucleotides directed against the mRNAs coding for
      alphaq, alpha11, beta1, beta3, gamma2, and gamma3 subunits selectively inhibited
      the increase in [Ca2+]i activated by alpha1-adrenoreceptors. A corresponding
      reduction of the expression of these G protein subunits was immunochemically
      confirmed. In experiments performed in Ca2+-free solution only cells injected
      with anti-alphaq antisense oligonucleotides displayed a reduction of the alpha1
      adrenoreceptor-induced Ca2+ release. In contrast, in Ca2+-containing solution,
      injection of anti-alpha11 antisense oligonucleotides suppressed the alpha1
      adrenoreceptor-induced stimulation of the store-operated Ca2+ influx. Agents that
      specifically bound Gbetagamma subunits (anti-betacom antibody and overexpression
      of a beta-adrenergic receptor kinase carboxyl-terminal fragment) had no effect on
      the alpha1-adrenoreceptor-induced signal transduction. Taken together, these
      results suggest that alpha1-adrenoreceptors utilize two different Galpha subunits
      to increase [Ca2+]i. Galphaq may activate phosphatidylinositol 4,5-bisphosphate
      hydrolysis and induce release of Ca2+ from intracellular stores. Galpha11 may
      enhance the Ca2+-activated Ca2+ influx that replenishes intracellular Ca2+
      stores.

PMID- 9030599
TI  - A single STAT recruitment module in a chimeric cytokine receptor complex is
      sufficient for STAT activation.
AB  - We established a system of receptor chimeras that enabled us to induce
      heterodimerization of different cytoplasmic tails. Fusion constructs were created
      that are composed of the extracellular parts of the interleukin-5 receptor alpha
      and beta chains, respectively, and the transmembrane and intracellular parts of
      gp130, the signal transducing chain of the interleukin-6 receptor complex. In COS
      7 transfectants we observed a dose-dependent interleukin-5-inducible STAT1
      activation for which the presence of both the alpha and the beta chain chimera
      was needed. No STAT activity was detected if one of the cytoplasmic tails of the
      receptor complex was deleted, indicating that STAT activity resulted from a
      receptor dimer rather than from higher receptor aggregates. We further
      investigated whether dimerization of STAT1 depends on the juxtaposition of two
      STAT recruitment modules in a receptor complex. We show that a receptor dimer
      with only a single STAT1 docking site was still able to lead to STAT1 activation.
      This indicates that the formation of a paired set of STAT binding sites in a
      receptor complex is not the prerequisite for STAT factor dimerization. Our
      findings are discussed in view of alternative STAT dimerization models.

PMID- 9030600
TI  - Affinity and kinetics of the interaction between soluble trimeric OX40 ligand, a
      member of the tumor necrosis factor superfamily, and its receptor OX40 on
      activated T cells.
AB  - OX40 ligand (OX40L) and OX40 are members of the tumor necrosis factor and tumor
      necrosis factor receptor superfamilies, respectively. OX40L is expressed on
      activated B and T cells and endothelial cell lines, whereas OX40 is expressed on
      activated T cells. A construct for mouse OX40L was expressed as a soluble protein
      with domains 3 and 4 of rat CD4 as a tag (sCD4-OX40L). It formed a homotrimer as
      assessed by chemical cross-linking and gel filtration chromatography.
      Radiolabeled sCD4-OX40L bound to activated mouse T cells with a high affinity (KD
      = 0.2-0.4 nM) and dissociated slowly (koff = 4 x 10(-5) s-1). The affinity and
      kinetics of the OX40L/OX40 interactions were studied using the BIAcoreTM
      biosensor, which measures macromolecular interactions in real time. The
      extracellular part of the OX40 antigen was expressed as a soluble monomeric
      protein and immobilized on the BIAcore sensor chip. sCD4-OX40L bound the OX40
      with a high affinity (KD = 3.8 nM), although this was lower than that determined
      on the surface of activated T cells (KD = 0.2-0.4 nM), where there is likely to
      be less restriction in mobility of the receptor. In the reverse orientation,
      sOX40 bound to immobilized sCD4-OX40L with a stoichiometry of 3.1 receptors to
      one ligand, with low affinity (KD = 190 nM) and had a relatively fast
      dissociation rate constant (koff = 2 x 10(-2) s-1). Thus if the OX40 receptor is
      cleaved by proteolysis, it will release any bound ligand and is unlikely to block
      re-binding of ligand to cell surface OX40 because of the low monomeric affinity.

PMID- 9030601
TI  - Functional antagonism between CCAAT/Enhancer binding protein-alpha and peroxisome
      proliferator-activated receptor-gamma on the leptin promoter.
AB  - The ob gene product, leptin, is a major hormonal regulator of appetite and fat
      cell mass. Recent work has suggested that the antidiabetic agents, the
      thiazolidinediones (TZ), which are also high affinity ligands of peroxisome
      proliferator-activated receptor-gamma (PPARgamma), inhibit leptin expression in
      rodents. To examine the effects of this class of drug on the leptin gene in
      adipocytes we performed Northern analysis on primary rat adipocytes cultured in
      the presence or absence of TZ. TZ reduced leptin mRNA levels by 75%. To determine
      whether this effect was mediated at the transcriptional level, we isolated 6510
      base pairs of 5'-flanking sequence of the leptin promoter and studied reporter
      constructs in primary rat adipocytes and CV-1 cells. Sequence analysis
      demonstrated the presence of a consensus direct repeat with a 1-base-pair gap
      site between -3951 and -3939 as well as a consensus CCAAT/enhancer binding
      protein (C/EBP) site between -55 and -47. Our functional analysis in transfected
      primary rat adipocytes demonstrates that, despite the presence of a canonical
      direct repeat with a 1-base-pair gap site, TZ alone decreases reporter gene
      expression of leptin promoter constructs ranging from -6510 to +9 to -65 to +9.
      In CV-1 cells, which contain endogenous PPARgamma, TZ treatment alone had little
      effect on these constructs. However, TZ treatment did inhibit C/EBPalpha-mediated
      transactivation of the leptin promoter. This down-regulation of leptin reporter
      constructs mapped to a -65 to +9 promoter fragment which binds C/EBPalpha in gel
      mobility shift assays but does not bind PPARgamma2 alone or as a heterodimer with
      9-cis-retinoic acid receptor. Conversely, the promoter (-5400 to +24 base pairs)
      of the aP2 gene, another adipocyte-specific gene, was induced 7.3-fold by TZ. Co
      transfection with C/EBPalpha minimally stimulated the aP2 promoter from basal
      levels but notably blocked activation by TZ. These data indicate that PPARgamma
      and C/EBPalpha can functionally antagonize each other on at least two separate
      promoters and that this mechanism may explain the down-regulation of leptin
      expression by thiazolidinediones.

PMID- 9030602
TI  - Sphingosine 1-phosphate induces platelet activation through an extracellular
      action and shares a platelet surface receptor with lysophosphatidic acid.
AB  - Sphingosine 1-phosphate (Sph-1-P) has been implicated as an intracellular second
      messenger in many studies. We investigated the metabolism of Sph-1-P and the
      mechanism by which Sph-1-P induces activation in enucleated and highly
      differentiated platelets. Platelets lack Sph-1-P lyase activity, possess
      persistently active sphingosine (Sph) kinase, and abundantly store Sph-1-P.
      Although exogenous Sph-1-P activated platelets, intracellular Sph-1-P, formed
      from exogenously added Sph by cytosolic Sph kinase, failed to do so. To support
      the notion that exogenous Sph-1-P stimulates platelets from outside, contact of
      platelet surfaces with immobilized Sph-1-P covalently linked to glass particles
      resulted in platelet activation. Furthermore, we detected the specific binding
      sites for radiolabeled Sph-1-P on the platelet surface, suggesting extracellular
      effects of Sph-1-P on plasma membrane receptors. This specific Sph-1-P binding
      was inhibited not by other sphingolipids but by lysophosphatidic acid (LPA), and
      platelet aggregation response to LPA was specifically desensitized by prior
      addition of Sph-1-P. Finally, internally stored Sph-1-P is released
      extracellularly upon stimulation, and the release correlated well with protein
      kinase C activation in intact platelets. These results suggest that Sph-1-P acts
      not intracellularly but intercellularly, following discharge from activated
      platelets, and shares a platelet surface receptor with LPA.

PMID- 9030603
TI  - In vitro assay and characterization of the farnesylation-dependent prelamin A
      endoprotease.
AB  - The 72-kDa nuclear lamina protein lamin A is synthesized as a 74-kDa farnesylated
      precursor. Conversion of this precursor to mature lamin A appears to be mediated
      by a specific endoprotease. Prior studies of overexpressed wild-type and mutant
      lamin A proteins in cultured cells have indicated that the precursor possesses
      the typical carboxyl-terminal S-farnesylated, cysteine methyl ester and that
      farnesylation is required for endoproteolysis to occur. In this report, we
      describe the synthesis of an S-farnesyl, cysteinyl methyl ester peptide
      corresponding to the carboxyl-terminal 18 amino acid residues of human prelamin
      A. This peptide acts as a substrate for the prelamin A endoprotease in vitro,
      with cleavage of the synthetic peptide at the expected site between Tyr657 and
      Leu658. Endoproteolytic cleavage requires the S-prenylated cysteine methyl ester
      and, in agreement with transfection studies, is more active with the farnesylated
      than geranylgeranylated cysteinyl substrate. N-Acetyl farnesyl methyl cysteine is
      shown to be a noncompetitive inhibitor of the enzyme. Taken together, these
      observations suggest that there is a specific farnesyl binding site on the enzyme
      which is not at the active site.

PMID- 9030604
TI  - Lysine 207 as the site of cross-linking between the 3'-end of Escherichia coli
      initiator tRNA and methionyl-tRNA formyltransferase.
AB  - The specific formylation of initiator methionyl-tRNA by methionyl-tRNA
      formyltransferase (MTF) is important for initiation of protein synthesis in
      Escherichia coli. In attempts to identify regions of MTF that come close to the
      3'-end of the tRNA, we oxidized 32P-3'-end-labeled E. coli initiator methionine
      tRNA with sodium metaperiodate and cross-linked it to MTF. The cross-linked MTF
      was separated from uncross-linked MTF by DEAE-cellulose chromatography, and the
      tRNA in the cross-linked MTF was hydrolyzed with nuclease P1 and RNase T1,
      leaving behind an oxidized fragment of [32P]AMP attached to MTF. Trypsin
      digestion of the cross-linked MTF followed by high pressure liquid chromatography
      of the digest yielded two peaks of radioactive peptides, I* and II*. These
      peptides were characterized by N- and/or C-terminal sequencing and by matrix
      assisted laser desorption ionization mass spectroscopy. Peptide I* contained
      amino acids Gln186-Lys210 with Lys207 as the site of the cross-link. Peptide II*,
      a partial digestion product, contained amino acids Gln186-Arg214 also with Lys207
      as the site of the cross-link. The molecular masses of peptides I* and II*
      indicate that the final product of the cross-linking reaction between the
      periodate-oxidized AMP moiety of the tRNA and Lys207 is most likely a morpholino
      derivative rather than a reduced Schiff's base.

PMID- 9030605
TI  - 2-Aminopurine unravels a role for pRB in the regulation of gene expression by
      transforming growth factor beta.
AB  - Transforming growth factor type beta (TGFbeta) is a pleiotropic factor that
      regulates different cellular activities including cell growth, differentiation,
      and extracellular matrix deposition. All the known effects of TGFbeta appear to
      be mediated by its interaction with cell surface receptors that possess a
      serine/threonine kinase activity. However, the intracellular signals that follow
      receptor activation and lead to the different cellular responses to TGFbeta are
      still largely unknown. On the basis of the different sensitivity to the protein
      kinase inhibitor 2-aminopurine and the phosphatase inhibitor okadaic acid, we
      identified two distinct pathways through which TGFbeta activates a genomic
      response. Consistently, 2-aminopurine prevented and okadaic acid potentiated the
      induction of JE by TGFbeta. The induction of PAI-1 and junB was instead
      potentiated by 2-aminopurine, after a transient inhibition and was unaffected by
      okadaic acid. The superinducing effect of 2-aminopurine required the presence of
      a functional RB protein since it was abolished in SV40 large T antigen
      transfected cells, absent in the BT549 and Saos-2 RB-defective cell lines, and
      restored in BT549 and Saos-2 cells after reintroduction of pRB. The effects of 2
      aminopurine on the TGFbeta inducible junB expression occur in all the cell lines
      examined suggesting that junB, and possibly other genes, can be regulated by
      TGFbeta through a distinct pRB-dependent pathway.

PMID- 9030606
TI  - Mft52, an acid-bristle protein in the cytosol that delivers precursor proteins to
      yeast mitochondria.
AB  - We have identified a novel protein, Mft52, in the cytosol of yeast cells. Mft52
      has a two-domain structure that includes a receptor-like carboxyl-terminal "acid
      bristle" domain, which binds basic, amphipathic mitochondrial targeting
      sequences. Native Mft52, purified from the cytosol of yeast cells, is found as a
      large particle eluting in the void volume of a Superose 6 gel filtration column.
      Fusion proteins, consisting of mitochondrial targeting sequences fused to
      nonmitochondrial passenger proteins, are targeted to mitochondria in wild-type
      yeast cells, but defects in the gene encoding Mft52 drastically reduce the
      delivery of these proteins to the mitochondria. We propose that Mft52 is a
      subunit of a particle that is part of a system of targeting factors and molecular
      chaperones mediating the earliest stages of protein targeting to the
      mitochondria.

PMID- 9030607
TI  - Spermatid-specific overexpression of the TATA-binding protein gene involves
      recruitment of two potent testis-specific promoters.
AB  - The gene encoding the TATA-binding protein, TBP, is highly overexpressed during
      the haploid stages of spermatogenesis in rodents. RNase protection analyses for
      mRNAs containing the previously identified first, second, and eighth exons
      suggested that most TBP mRNAs in testis did not initiate at the first exon used
      in somatic cells (here designated exon 1C). Using a sensitive ligation-mediated
      cDNA amplification method, 5' end variants of TBP mRNA were identified, and the
      corresponding cDNAs were cloned from liver and testis. In liver, a single
      promoter/first exon is used to generate a steady-state level of roughly five
      molecules of TBP mRNA per diploid cell equivalent. In testis, we detect modest up
      regulation of the somatic promoter and recruitment of at least five other
      promoters. Three of the alternative promoter/first exons, including 1C and two of
      the testis-specific promoter/first exons, 1D and 1E, contribute roughly
      equivalent amounts of mRNA which, in sum, account for greater than 90% of all TBP
      mRNA in testis. As a result, round spermatids contain an estimated 1000 TBP mRNA
      molecules per haploid cell. Testis TBP mRNA also exhibits several low abundance
      5' end splicing variants; however, all detected TBP mRNA leader sequences splice
      onto the common exon 2 and are expected to initiate translation at the same site
      within exon 2. The precise locations of the three major initiation exons are
      mapped on the gene. The identification of the strong testis-specific
      promoter/first exons will be important for understanding spermatid-specific tbp
      gene regulation.

PMID- 9030608
TI  - NH2-terminal proline acts as a nucleophile in the glycosylase/AP-lyase reaction
      catalyzed by Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) protein.
AB  - Formamidopyrimidine-DNA glycosylase (Fpg) protein plays a prominent role in the
      repair of oxidatively damaged DNA in Escherichia coli. The protein possesses
      three enzymatic activities, hydrolysis of the N-glycosidic bond (DNA
      glycosylase), beta-elimination (AP lyase), and delta-elimination; these functions
      act in a concerted manner to excise oxidized deoxynucleosides from duplex DNA.
      Schiff base formation between the enzyme and substrate has been demonstrated
      (Tchou, J., and Grollman, A. P. (1995) J. Biol. Chem. 270, 11671-11677); this
      protein-DNA complex can be trapped by reduction with sodium borohydride. By
      digesting the stable, covalently linked intermediate with proteases and
      determining the accurate mass of the products by negative electrospray ionization
      mass spectrometry, we show that the N-terminal proline of Fpg protein is linked
      to DNA and, therefore, is identified as the nucleophile that initiates the
      catalytic excision of oxidized bases from DNA. This experimental approach may be
      applicable to the analysis of other protein-DNA complexes.

PMID- 9030609
TI  - Introduction of plasmid DNA into isolated mitochondria by electroporation. A
      novel approach toward gene correction for mitochondrial disorders.
AB  - Mitochondrial disorders are a large group of phenotypically heterogeneous
      diseases. An understanding of their molecular basis would benefit greatly from
      the ability to manipulate the mitochondrial genome and/or to introduce functional
      exogenous DNA into mitochondria. As a first step toward this approach, we have
      used electroporation to introduce a 7.2-kilobase plasmid DNA into isolated
      functional mitochondria. Transfer of the DNA at field strengths between 8 and 20
      kV/cm was investigated by Southern blot analysis. Maximal plasmid internalization
      was achieved at a field strength of 14 kV/cm. The functional integrity of the
      mitochondria after electroporation was verified by enzymatic assays of specific
      mitochondrial marker enzymes and by measuring respiratory control. At field
      strengths above 12 kV/cm, an increasing mitochondrial destruction was observed.
      12 kV/cm was found to be optimal for the most efficient plasmid internalization
      while still retaining the functional integrity of the mitochondria. At this field
      strength, about half of the internalized plasmid was found in the inner membrane
      or mitochondrial matrix, as determined by immunoelectron microscopy and Southern
      blot analysis of electroporated mitochondria treated with digitonin. We estimate
      that on average one plasmid molecule/mitochondrion reaches the matrix or inner
      membrane.

PMID- 9030610
TI  - Soluble human urokinase receptor is composed of two active units.
AB  - The mechanism by which single-chain urokinase (scuPA) binds to its receptor
      (uPAR) is incompletely understood. We report that a fragment comprising the first
      domain of recombinant soluble uPAR (sDI) as well as a fragment comprising the
      remaining domains (sDII-DIII) competes with the binding of recombinant full
      length soluble uPAR (suPAR) to scuPA with an IC50 = 253 nM and an IC50 = 1569,
      respectively. sDII-III binds directly to scuPA with Kd = 238 nM. Binding of scuPA
      to each fragment also induces the expression of plasminogen activator activity.
      sDI and sDII-DIII (200 nM each) induced activity equal to 66 and 36% of the
      maximum activity induced by full-length suPAR (5 nM), respectively. Each fragment
      also stimulates the binding of scuPA to cells lacking endogenous uPAR. Although
      scuPA binds to sDI and to sDII-DIII through its amino-terminal fragment, the
      fragments act synergistically to inhibit the binding of suPAR and to stimulate
      plasminogen activator activity. Furthermore, sDII-DIII retards the velocity and
      alters the pattern of cleavage of sDI by chymotrypsin. These results suggest that
      binding of scuPA to more than one epitope in suPAR is required for its optimal
      activation and association with cell membranes.

PMID- 9030611
TI  - The kinetic mechanism of serpin-proteinase complex formation. An intermediate
      between the michaelis complex and the inhibited complex.
AB  - Serine proteinase inhibitors (serpins) form enzymatically inactive, 1:1 complexes
      (denoted E*I*) with their target proteinases that release free enzyme and cleaved
      inhibitor only very slowly. The mechanism of E*I* formation is incompletely
      understood and continues to be a source of controversy. Kinetic evidence exists
      that formation of E*I* proceeds via a Michaelis complex (E.I) and so involves at
      least two steps. In this paper, we determine the rate of E*I* formation from
      alpha-chymotrypsin and alpha1-antichymotrypsin using two approaches: first, by
      stopped-flow spectrofluorometric monitoring of the fluorescent change resulting
      from reaction of alpha-chymotrypsin with a fluorescent derivative of alpha1
      antichymotrypsin (derivatized at position P7 of the reactive center loop); and
      second, by a rapid mixing/quench approach and SDS-polyacrylamide gel
      electrophoresis analysis. In some cases, serpins are both substrates and
      inhibitors of the same enzyme. Our results indicate the presence of an
      intermediate between E.I and E*I* and suggest that the partitioning step between
      inhibitor and substrate pathways precedes P1-P1' cleavage.

PMID- 9030612
TI  - Fibrinogen is a ligand for integrin alpha5beta1 on endothelial cells.
AB  - Previous studies have shown that fibrinogen can associate with endothelial cells
      via an Arg-Gly-Asp (RGD) recognition specificity. In the present study, we have
      characterized the specificity of fibrinogen binding to endothelial cells under
      different cation conditions. Fibrinogen binding to suspended endothelial cells
      was selectively supported by Mn2+ and was suppressed by Ca2+. The Mn2+-supported
      interaction was completely inhibited by RGD peptides but not by alphavbeta3
      blocking monoclonal antibodies. In contrast, the interaction was completely
      blocked by two alpha5beta1 monoclonal antibodies. This interaction was not
      mediated by fibronectin bound to the integrin; could be demonstrated with
      purified alpha5beta1; and also was observed with a second alpha5beta1-bearing
      cell type, platelets. The binding of fibrinogen to alpha5beta1 on endothelial
      cells in the presence of Mn2+ was time-dependent, specific, saturable, and of
      high affinity (Kd = 65 nM). By employing anti-peptide monoclonal antibodies, the
      carboxyl-terminal RGD sequence at Aalpha 572-574 was implicated in fibrinogen
      recognition by alpha5beta1. Two circumstances were identified in which
      alpha5beta1 interacted with fibrinogen in the presence of Ca2+: when the receptor
      was activated with monoclonal antibody (8A2) or when the fibrinogen was presented
      as an immobilized substratum. These results identify fibrinogen as a ligand for
      alpha5beta1 on endothelial and other cells, an interaction which may have broad
      biological implications.

PMID- 9030613
TI  - Formation of oligomers containing the beta3 and beta4 subunits of the rat
      nicotinic receptor.
AB  - The role of the beta3 and beta4 subunits of the nicotinic acetylcholine receptor
      in brain is still unclear. We investigated nicotinic receptor structure with
      antibodies directed against unique regions of the beta3 and beta4 subunits of the
      rat nicotinic acetylcholine receptor. Anti-beta4 detected a single band of 66 kDa
      in most regions of the brain that was strongest in striatum and cerebellum. The
      60 kDa beta3 subunit was detected primarily in striatum and cerebellum, and
      faintly in hippocampus. Immunoprecipitation experiments established that the two
      subunits were coassembled in the cerebellum along with the beta2 subunit.
      Antibodies against the alpha4, beta2, beta3, and beta4 subunits
      immunoprecipitated approximately 75% of the bungarotoxin-insensitive nicotinic
      receptor from cerebellar extracts as determined by nicotine-dependent
      acetylcholine binding. Transfection of COS cells with cDNAs for these four
      subunits induced expression of a high affinity nicotinic receptor. Omission of
      only a single subunit from the transfection affected either the Bmax or the
      apparent KD of the receptor. Our data suggest that the beta3 subunit functions as
      a structural entity that links a relatively unstable alpha4beta2 heterodimer to a
      more stable alpha4beta4 heterodimer. The agonist-binding site formed by
      alpha4beta2 has a much greater affinity than does that formed by alpha4beta4. In
      this respect, nicotinic receptors that contain the beta3 subunit are structurally
      homologous to the muscle nicotinic receptor.

PMID- 9030614
TI  - Fragile X mental retardation protein: nucleocytoplasmic shuttling and association
      with somatodendritic ribosomes.
AB  - Fragile X syndrome, a leading cause of inherited mental retardation, is
      attributable to the unstable expansion of a CGG-repeat within the FMR1 gene that
      results in the absence of the encoded protein. The fragile X mental retardation
      protein (FMRP) is a ribosome-associated RNA-binding protein of uncertain function
      that contains nuclear localization and export signals. We show here detailed
      cellular localization studies using both biochemical and immunocytochemical
      approaches. FMRP was highly expressed in neurons but not glia throughout the rat
      brain, as detected by light microscopy. Although certain structures, such as
      hippocampus, revealed a strong signal, the regional variation in staining
      intensity appeared to be related to neuron size and density. In human cell lines
      and mouse brain, FMRP co-fractionated primarily with polysomes and rough
      endoplasmic reticulum. Ultrastructural studies in rat brain revealed high levels
      of FMRP immunoreactivity in neuronal perikarya, where it is concentrated in
      regions rich in ribosomes, particularly near or between rough endoplasmic
      reticulum cisternae. Immunogold studies also provided evidence of
      nucleocytoplasmic shuttling of FMRP, which was localized in neuronal nucleoplasm
      and within nuclear pores. Moreover, labeling was observed in large- and small
      caliber dendrites, in dendritic branch points, at the origins of spine necks, and
      in spine heads, all known locations of neuronal polysomes. Dendritic
      localization, which was confirmed by co-fractionation of FMRP with synaptosomal
      ribosomes, suggests a possible role of FMRP in the translation of proteins
      involved in dendritic structure or function and relevant for the mental
      retardation occurring in fragile X syndrome.

PMID- 9030615
TI  - Insulin-like growth factor and potassium depolarization maintain neuronal
      survival by distinct pathways: possible involvement of PI 3-kinase in IGF-1
      signaling.
AB  - Cultured cerebellar granule neurons die by apoptosis when switched from a medium
      containing an elevated level of potassium (K+) to one with lower K+ (5 mM). Death
      resulting from the lowering of K+ can be prevented by insulin-like growth factor
      (IGF-1). To understand how IGF-1 inhibits apoptosis and maintains neuronal
      survival, we examined the role of phosphoinositide 3-kinase (PI 3-kinase).
      Activation of PI 3-kinase has been shown previously to be required for NGF
      mediated survival in the PC12 pheochromocytoma cell line. We find that in primary
      neurons, IGF-1 treatment leads to a robust activation of PI 3-kinase, as judged
      by lipid kinase assays and Western blot analysis. Activation of PI 3-kinase is
      likely to occur via tyrosine phosphorylation of the insulin receptor substrate
      protein. Treatment with two chemically distinct inhibitors of PI 3-kinase,
      wortmannin and LY294002, reduces PI 3-kinase activation by IGF-1 and inhibits its
      survival-promoting activity, suggesting that PI 3-kinase is necessary for IGF-1
      mediated survival. Death resulting from PI 3-kinase blockade is accompanied by
      DNA fragmentation, a hallmark of apoptosis. Furthermore, neurons subjected to PI
      3-kinase blockade can be rescued by transcriptional and translation inhibitors,
      suggesting that IGF-1-mediated activation of PI 3-kinase leads to a suppression
      of "killer gene" expression. In sharp contrast to IGF-1, elevated K+ does not
      activate PI 3-kinase and can maintain neuronal survival in the presence of PI 3
      kinase inhibitors. Therefore, survival of granule neurons can be maintained by PI
      3-kinase dependent (IGF-1-activated) and independent (elevated K+-activated)
      pathways.

PMID- 9030617
TI  - Combinations of AMPA receptor subunit expression in individual cortical neurons
      correlate with expression of specific calcium-binding proteins.
AB  - The functional properties of AMPA-type glutamate receptors are determined by
      their subunit composition. We detected the expression of the AMPA receptor
      subunits (GluR1-GluR4) in neurons in the somatosensory cortex of adult rats by
      combining nonradioactive in situ hybridization using digoxigenin-labeled RNA
      probes of GluR1 and GluR2 with immunocytochemistry using specific antibodies
      against GluR1, GluR2/3, and GluR4. On the basis of differential expression of the
      GluR1 and GluR2 subunits, we classified the cortical neurons into four
      categories. To correlate the differential expression of AMPA receptor subunits in
      each neuron with that of two calcium-binding proteins, parvalbumin and calbindin
      D28k, we used a triple-labeling method. The majority of cortical neurons (
      approximately 2/3) showed expression of GluR2 and undetectable expression of
      GluR1. GluR1-/GluR2-expressing neurons and GluR1-expressing/GluR2-undetectable
      neurons comprised approximately 1/10 each. Regarding the morphology, most GluR1
      undetectable/GluR2-expressing neurons were pyramidal cells in layers II/III, V,
      and VI, whereas most GluR1-expressing/GluR2-undetectable neurons were
      nonpyramidal cells in layers II-VI. The GluR1-/GluR2-expressing neurons were
      either pyramidal or nonpyramidal. The majority of GluR1-/GluR2-expressing
      nonpyramidal cells was intensely stained with monoclonal antibody against
      calbindin-D28k, and one-half of the GluR1-undetectable/GluR2-expressing pyramidal
      neurons in layer II/III were lightly stained with this antibody. Most of GluR1
      expressing/GluR2-undetectable neurons possessed parvalbumin immunoreactivity.
      These results indicate that neurons in the rat somatosensory cortex express
      differential combinations of GluR subunits, which correlate with the specific
      expression of the calcium-binding proteins.

PMID- 9030616
TI  - Cloning and expression of a rat brain interleukin-1beta-converting enzyme (ICE)
      related protease (IRP) and its possible role in apoptosis of cultured cerebellar
      granule neurons.
AB  - Several members of the IL-1beta-converting enzyme (ICE) family of proteases
      recently have been implicated in the intracellular cascade mediating the
      apoptotic death of various cell types. It is unclear, however, whether ICE
      related proteases are involved in apoptosis of mammalian neurons and, if so, how
      they are activated. Here we report the cloning of an ICE-related protease (IRP)
      from rat brain, which displays strong sequence identity to human CPP32. In situ
      hybridization histochemistry reveals that this IRP mRNA is expressed in neuron
      enriched regions of the developing and adult rat brain but is profoundly
      downregulated in the adult (compared with developing) brain. To investigate
      whether this IRP is involved in the death of neurons in the developing brain, we
      studied IRP expression in cultured cerebellar granule neurons. In cultured
      cerebellar granule neurons, reduction of extracellular K+ reliably induces
      apoptosis and stimulates overexpression of IRP mRNA. The latter is especially
      prominent 4 hr after switching from high K+ to low K+ medium. The expression of
      IRP mRNA was maintained at this level for at least 8 hr and was followed by
      apoptotic death of these neurons. Induction of IRP mRNA and cell death are
      blocked completely by adding depolarizing concentrations of K+ </=90 min after
      switching to low K+ medium (i.e., before the commitment point for apoptosis) and
      partially blocked by brain-derived neurotrophic factor (BDNF), which also
      partially rescues granule neurons from low K+-induced apoptosis. In addition,
      overexpression of IRP cDNA in HeLa cells results in cell death accompanied by
      strong internucleosomal cleavage of DNA, a typical feature of apoptosis. Finally,
      we detected cleavage of the putative death substrate poly (ADP-ribose) polymerase
      (PARP), beginning 8 hr after changing from high K+ to low K+ medium, coinciding
      with the time course of induced expression of the IRP gene. Our data suggest that
      transcriptional activation of IRP could be one of the mechanisms involved in the
      apoptotic death of cerebellar granule neurons.

PMID- 9030618
TI  - Identification of a vesicular pool of calcium channels in the bag cell neurons of
      Aplysia californica.
AB  - To study the molecular mechanism of calcium current modulation in the bag cell
      neurons of Aplysia californica, we have identified calcium channel subtypes
      expressed in these cells and analyzed their distribution using channel-specific
      antibodies. Using PCR to amplify reverse-transcribed RNA from bag cell clusters,
      we identified two classes of calcium channel alpha1 subunit. One, BCCa-I, belongs
      to the ABE subfamily of calcium channels, whereas the other, BCCa-II, belongs to
      the SCD subfamily. Antibodies generated against the bag cell calcium channels
      recognize membrane proteins of approximately 210 and 280 kDa on immunoblots. Both
      channels are expressed in the bag cell clusters as well as in other parts of the
      Aplysia nervous system. BCCa-II also localizes to glia and muscle. The
      subcellular distribution of the two channel types is strikingly different.
      Antibody staining of bag cell neurons in primary culture shows that BCCa-II is
      present on the plasma membrane, whereas BCCa-I has a punctate, intracellular
      distribution consistent with a vesicular localization. The BCCa-I-containing
      vesicles are found in bag cell neuron somata and growth cones and occasionally in
      neuritic hotspots. Their distribution is similar but not identical to that of
      LysoTracker Red, a marker for acidic organelles, but unlike that of dense-core
      vesicles containing egg-laying hormone. The vesicular channels may represent the
      protein kinase C-sensitive calcium channels of bag cell neurons that are believed
      to enhance hormonal release during electrical activity.

PMID- 9030619
TI  - Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly
      of multimeric protein complexes.
AB  - The assembly of multimeric protein complexes that include vesicle-associated
      membrane protein 2 (VAMP-2) and the plasma membrane proteins syntaxin 1A and
      synaptosome-associated protein of 25 kDa (SNAP-25) are thought to reflect the
      biochemical correlates of synaptic vesicle targeting, priming, or fusion. Using a
      variety of protein-protein interaction assays and a series of deletion and point
      mutations, we have investigated the domains of VAMP-2 required for the formation
      of binary complexes with either syntaxin 1A or SNAP-25 and ternary complexes with
      both syntaxin 1A and SNAP-25. Deletions within the central conserved domain of
      VAMP-2 eliminated binding to either syntaxin 1A or both syntaxin 1A and SNAP-25.
      Although all of the deletion mutants were able to form ternary complexes, only
      some of these complexes were resistant to denaturation in sodium dodecyl sulfate.
      These results demonstrate that cooperative interactions result in the formation
      of at least two biochemically distinct classes of ternary complex. Two point
      mutations previously shown to have effects on the intracellular trafficking of
      VAMP-2 (M46A, reduced endocytosis and sorting to synaptic vesicles; N49A,
      enhanced sorting to synaptic vesicles) lie within a domain required for both
      syntaxin 1A and SNAP-25 binding. Syntaxin 1A and SNAP-25 binding was reduced by
      the M46A mutation and enhanced by the N49A mutation, suggesting that a
      correlation exists between the membrane-trafficking phenotype of the two VAMP-2
      point mutants and their competence to form complexes with either syntaxin 1A or
      SNAP-25.

PMID- 9030620
TI  - D-serine as a neuromodulator: regional and developmental localizations in rat
      brain glia resemble NMDA receptors.
AB  - D-Serine is localized in mammalian brain to a discrete population of glial cells
      near NMDA receptors, suggesting that D-serine is an endogenous agonist of the
      receptor-associated glycine site. To explore this possibility, we have compared
      the immunohistochemical localizations of D-serine, glycine, and NMDA receptors in
      rat brain. In the telencephalon, D-serine is concentrated in protoplasmic
      astrocytes, which are abundant in neuropil in close vicinity to NMDA receptor
      2A/B subunits. Ultrastructural examination of the CA1 region of hippocampus
      reveals D-serine in the cytosolic matrix of astrocytes that ensheath neurons and
      blood vessels, whereas NR2A/B is concentrated in dendritic spines. By contrast,
      glycine immunoreactivity in telencephalon is the lowest in brain. During
      postnatal week 2, D-serine levels in cerebellum are comparable to those in adult
      cerebral cortex but fall to undetectable levels by day 26. During week 2, we
      observe parallel ontogeny of D-serine in Bergmann glia and NR2A/B in Purkinje
      cells, suggesting a role for astrocytic D-serine in NMDA receptor-mediated
      synaptogenesis. D-Serine in the radial processes of Bergmann glia is also well
      positioned to regulate NMDA receptor-dependent granule cell migration. In the
      inner granule layer, D-serine is found transiently in protoplasmic astrocytes
      surrounding glomeruli, where it could regulate development of the mossy
      fiber/granule cell synapse. D-Serine seems to be the endogenous ligand of glycine
      sites in the telencephalon and developing cerebellum, whereas glycine
      predominates in the adult cerebellum, olfactory bulb, and hindbrain.

PMID- 9030621
TI  - Coexpression of two odorant-binding protein homologs in Drosophila: implications
      for olfactory coding.
AB  - Odorant-binding proteins (OBPs) are small soluble proteins present in the aqueous
      medium surrounding olfactory receptor neurons. Their function in olfaction is
      still unknown: they have been proposed to facilitate the transit of hydrophobic
      molecules to olfactory receptors, to deactivate the odorant stimulus, and/or to
      play a role in chemosensory coding. In this study we examine the genomic
      organization and expression patterns of two olfactory-specific genes (OS-E and OS
      F) of Drosophila melanogaster, the products of which are members of a protein
      family in Drosophila sharing sequence similarity with moth OBPs. We show that the
      OS-E and OS-F transcription units are located <1 kb apart. They are oriented in
      the same direction and display a similar intron-exon organization. Expression of
      both OS-E and OS-F proteins is restricted spatially to the ventrolateral region
      of the Drosophila antenna. Within this region both OS-E and OS-F proteins are
      expressed within two different types of sensory hairs: in most, if not all,
      sensilla trichodea and in approximately 40% of the interspersed small sensilla
      basiconica. We consistently observe that OS-E and OS-F are coexpressed,
      indicating that an individual sensillum can contain more than one odorant-binding
      protein. The functional significance of the observed expression pattern and its
      implications for olfactory coding are discussed.

PMID- 9030622
TI  - Facilitation of N-type calcium current is dependent on the frequency of action
      potential-like depolarizations in dissociated cholinergic basal forebrain neurons
      of the guinea pig.
AB  - Voltage-dependent inhibition of high voltage-activated (HVA) calcium currents by
      G-proteins can be transiently relieved (facilitated) by strong depolarizing
      prepulses. However, with respect to the physiological significance of
      facilitation, it remains to be established if it can be induced by action
      potentials (AP) in central neurons. With the use of whole-cell recordings of
      dissociated cholinergic basal forebrain neurons of the guinea pig, it is shown
      that the GTPgammaS-inhibited HVA currents that occur through N-ethylmaleimide
      (NEM)-sensitive Gi-Go subtypes of G-proteins can be facilitated. Furthermore,
      although different types of HVA channels are present in these neurons,
      facilitation occurred mostly through disinhibition of the N-type current. On the
      basis of data indicating that the recovery from facilitation was relatively slow,
      we tested if more physiological stimuli that crudely mimicked APs (2 msec long
      depolarizations to 40 mV from a holding of -50 mV) potentially could induce
      facilitation of HVA currents inhibited by GTPgammaS and cholinergic agonists.
      Indeed, evidence is provided that the extent of facilitation is dependent on both
      the number and frequency of AP-like depolarizations. These results suggest that
      firing rates and patterns of discharge of neurons could influence their
      responsiveness to transmitters acting on N-type HVA calcium channels.

PMID- 9030623
TI  - Ectopic alpha2-adrenoceptors couple to N-type Ca2+ channels in axotomized rat
      sensory neurons.
AB  - Dorsal root ganglion (DRG) neurons from control rats or from rats in which the
      sciatic nerve had been sectioned were studied by whole-cell recording techniques.
      Noradrenaline (10-100 micro;M) activated beta-adrenoceptors and increased L-type
      Ca2+ channel current in control DRG cells, but this had little effect on
      excitability (the number of action potentials generated by a pulse of current at
      rheobasic strength). By contrast, in cells from nerve-damaged animals,
      noradrenaline activated alpha2-adrenoceptors, suppressed N-type Ca2+ channel
      current, and increased excitability. In axotomized cells, it also reduced total
      outward current recorded at +70 mV. Because noradrenaline did not affect total
      outward current recorded in the presence of the Ca2+ channel blocker Cd2+ (0. 5-1
      mM), its effects on excitability may result from reduction of Ca2+-sensitive K+
      conductance(s) following suppression of N-type Ca2+ channel current. The
      strongest effects of noradrenaline were seen in small cells and in cells from
      animals that exhibited autotomy, a self-mutilatory behavior that can accompany
      peripheral nerve damage. Because many of these small DRG cells may be involved in
      the transmission of nociceptive information, changes in coupling between Ca2+
      channels and adrenoceptors may contribute to the generation of the ectopic
      sensory nerve activity that has been implicated in the etiology of neuropathic
      pain.

PMID- 9030624
TI  - Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is
      induced during Wallerian degeneration.
AB  - Schwann cell dedifferentiation and proliferation is a prerequisite to axonal
      regeneration in the injured peripheral nervous system. The neuregulin (NRG)
      family of growth and differentiation factors may play a particularly important
      role in this process, because these axon-associated molecules are potent Schwann
      cell mitogens and differentiation factors in vitro. We have examined Schwann cell
      DNA synthesis and the expression of NRGs and their receptors, the erbB membrane
      tyrosine kinases, in rat sciatic nerve, sensory ganglia, and spinal cord 0-30 d
      postaxotomy. Analysis of NRG cDNAs from these tissues revealed several novel
      splice variants and showed that cells endogenous to injured nerve express NRG
      mRNAs. A selective induction of mRNAs encoding the glial growth factor (GGF)
      subfamily of NRGs occurs in nerve beginning 3 d postaxotomy and thus coincides
      with the onset of Schwann cell DNA synthesis. In later stages of Wallerian
      degeneration, however, Schwann cell mitogenesis markedly decreases, whereas
      elevated GGF expression persists. Of the four known erbB kinases, Schwann cells
      express both erbB2 and erbB3 receptors over the entire interval studied.
      Expression of erbB2 and erbB3 is coordinately induced in response to axotomy,
      indicating that Schwann cell responses to NRGs may be modulated by changes in
      receptor density. Neuregulin (including transmembrane precursors) and erbB
      protein are associated with Schwann cells postaxotomy. Thus, in contrast to the
      concept of NRGs as axon-associated mitogens, our findings suggest that NRGs
      produced by Schwann cells themselves may be partially responsible for Schwann
      cell proliferation during Wallerian degeneration, probably acting via autocrine
      or paracrine mechanisms.

PMID- 9030625
TI  - Involvement of MAP kinase in angiotensin II-induced phosphorylation and
      intracellular targeting of neuronal AT1 receptors.
AB  - MAP kinase stimulation is a key signaling event in the AT1 receptor (AT1R)
      mediated chronic stimulation of tyrosine hydroxylase and norepinephrine
      transporter in brain neurons by angiotensin II (Ang II). In this study, we
      investigated the involvement of MAP kinase in AT1R phosphorylation to further our
      understanding of these persistent neuromodulatory actions of Ang II. Ang II
      caused a time-dependent phosphorylation of neuronal AT1R. This phosphorylation
      was associated with internalization and translocation of AT1R into the nucleus.
      MAP kinase also stimulated phosphorylation of neuronal AT1R. The conclusion that
      MAP kinase participates in neuronal AT1R phosphorylation and its targeting into
      the nucleus is supported further by the following. (1) MAP kinase-mediated
      phosphorylation of AT1R was blocked by the AT1R antagonist losartan; (2) AT1R co
      immunoprecipitated with MAP kinase; (3) MAP kinase-kinase inhibitor PD98059
      attenuated Ang II-induced phosphorylation of AT1R; and (4) PD98059 blocked Ang II
      induced nuclear translocation of AT1Rs. In summary, these observations
      demonstrate that Ang II-induced phosphorylation of AT1R is mediated by its
      activation of MAP kinase. A possible role of AT1R translocation into the nucleus
      on persistent neuromodulatory actions of Ang II has been discussed.

PMID- 9030626
TI  - Calcium-containing organelles display unique reactivity to chemical stimulation
      in cultured hippocampal neurons.
AB  - Cultured rat hippocampal neurons grown on glass coverslips for 1-3 weeks were
      loaded with the calcium-sensitive fluorescent dye Fluo-3 and viewed with a
      confocal laser scanning microscope. Large pyramidal-shaped neurons were found to
      contain dye-accumulating organelles in their somata, primarily around nuclei and
      near the base of their primary dendrites. These organelles varied in size and
      increased in density over weeks in culture, and were not colocalized with the
      endoplasmic reticulum or with mitochondria. The Fluo-3 fluorescence in these
      calcium-containing organelles (CCOs) was transiently quenched by exposure to
      Mn2+, indicating that the dye is a genuine [Ca2+] reporter and is not just a site
      of accumulating Fluo-3 dye. Recovery of fluorescence in the CCOs after washout of
      Mn2+ involved activation of a thapsigargin-sensitive process. CCOs responded to
      stimuli that evoke a rise of cytosolic [Ca2+] ([Ca]i) in a unique manner;
      perfusion of caffeine caused a prolonged rise of [Ca] in the CCOs ([Ca]C),
      whereas it caused only a transient rise of [Ca]i. Pulse application of caffeine
      also caused a faster effect on [Ca]C than on [Ca]i. Glutamate caused a transient
      rise of both [Ca]i and [Ca]C, followed by a prolonged fall of only [Ca]C to below
      rest level. This fall was blocked by preincubation with thapsigargin. Ryanodine
      blocked the cytosolic effects of caffeine but not its effect on [C]C. A clear
      distinction between CCOs and the known calcium stores was seen in digitonin
      permeabilized cells; in these, remaining Fluo-3 reported changes in store
      calcium, i.e., caffeine caused a reduction in Fluo-3 fluorescence in
      permeabilized cells, whereas it still caused an increase in [Ca]C. A possible
      role of CCOs in regulation of release of calcium from ryanodine-sensitive stores
      was indicated by the observation that CCO-containing cells exhibited a larger and
      faster response to caffeine than cells that did not have them. We propose that
      CCOs constitute a unique functional compartment involved in release of calcium
      from calcium-sensitive stores.

PMID- 9030628
TI  - Dendritic and postsynaptic localizations of glycine receptor alpha subunit mRNAs.
AB  - Some synaptic neurotransmitter receptors, such as those for glycine, have somato
      dendritic distributions. Although the machinery for protein synthesis and several
      mRNAs are present in dendrites and close to synapses in central neurons, so far
      the mRNAs for neurotransmitter receptors have not been found unequivocally in
      dendrites. The glycine receptor (GlyR), a ligand-gated channel mediating a
      chloride-dependent inhibition, is composed of transmembrane alpha and beta
      subunits. GlyRs are only present at glycinergic postsynaptic differentiation,
      where they are stabilized by the associated protein gephyrin. With light
      nonradioactive in situ hybridization (ISH), we observe that GlyR alpha subunit
      mRNAs are present in both somata and dendrites of most neurons of the ventral
      horn of rat spinal cord, whereas the beta subunit and gephyrin mRNAs are
      predominantly in somata. Interestingly, within dendrites GlyR alpha subunit mRNAs
      form aggregates that are mostly localized peripherally to the dendritic axial
      core. Electron microscopic ISH shows that GlyR alpha subunit mRNAs are associated
      with postsynaptic differentiations. At these sites, the GlyR alpha subunit mRNAs
      are detected in close association with subsynaptic cisternae. This targeting of
      alpha subunit mRNAs to postsynaptic domains could provide a means of dynamically
      modulating synaptic efficacy by changing the composition and the density of
      receptors at glycinergic synapses.

PMID- 9030627
TI  - Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid
      peptide.
AB  - Studies from several laboratories have generated evidence suggesting that
      oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD). The
      finding that the amyloid beta protein (Abeta) has neurotoxic properties and that
      such effects are, in part, mediated by free radicals has provided insights into
      mechanisms of cell death in AD and an avenue to explore new therapeutic
      approaches. In this study we demonstrate that melatonin, a pineal hormone with
      recently established antioxidant properties, is remarkably effective in
      preventing death of cultured neuroblastoma cells as well as oxidative damage and
      intracellular Ca2+ increases induced by a cytotoxic fragment of Abeta. The
      effects of melatonin were extremely reproducible and corroborated by multiple
      quantitative methods, including cell viability studies by confocal laser
      microscopy, electron microscopy, and measurements of intracellular calcium
      levels. The importance of this finding is that, in contrast to conventional
      antioxidants, melatonin has a proposed physiological role in the aging process.
      Secretion levels of this hormone are decreased in aging and more severely reduced
      in AD. The reported phenomenon may be of therapeutic relevance in AD.

PMID- 9030629
TI  - Rapid coupling of calcium release to depolarization in Limulus polyphemus ventral
      photoreceptors as revealed by microphotolysis and confocal microscopy.
AB  - Microphotolysis and confocal microscopy were used to investigate the timing of
      calcium release and of the electrical response in Limulus polyphemus ventral
      photoreceptors. The fluorescent dyes Fluo-3 and Calcium Green-5N were used to
      monitor local Ca2+ elevations. Photolysis of caged inositol trisphosphate (InsP3)
      close to the plasma membrane of the light-sensitive rhabdomeral (R-) lobe
      resulted in Ca2+ elevation within 10-20 msec, 20-45 msec before the physiological
      response to light normally would be detected. Inward ionic current flow and
      depolarization followed InsP3-induced calcium release within 2.5 +/- 3.3 msec.
      Voltage-clamping the cells and removal of extracellular Ca2+ did not affect the
      timing of the Ca2+ elevation that followed the photolysis of caged InsP3 or its
      relationship to the electrical response. In contrast to the physiological
      response to light, which only released calcium within the R-lobe, photolysis of
      InsP3 elevated Cai in both lobes, although with much greater effect in the R
      lobe, as compared with the bulk of the A-lobe, suggesting the presence of InsP3
      sensitive calcium stores in both lobes. Photolysis of caged calcium [o
      nitrophenyl EGTA (NPE)] at the edge of the R-lobe activated an inward ionic
      current within 1.8 +/- 0.7 msec. This NPE-induced current reversed at a membrane
      potential of 10 +/- 6 mV in the range typical of that of the light-activated
      current under physiological conditions. Calcium release, therefore, activates an
      inward current rapidly enough to contribute to the electrical response to light.

PMID- 9030630
TI  - Pharmacology and distribution of norepinephrine transporters in the human locus
      coeruleus and raphe nuclei.
AB  - The norepinephrine transporter (NET) is a site of action for tricyclic
      antidepressant drugs and for drugs of abuse such as amphetamine and cocaine. In
      this study, the binding of [3H]nisoxetine to NETs in the noradrenergic cell
      group, the locus coeruleus, and the serotonergic cell groups, the dorsal raphe
      nuclei, was measured autoradiographically in postmortem human brain.
      [3H]nisoxetine binding was unevenly distributed along the rostral-caudal axis of
      the locus coeruleus and correlated positively with numbers of neuromelanin
      containing (noradrenergic) cells along the axis of the locus coeruleus within
      individuals. Binding densities of [3H]nisoxetine in dorsal raphe nuclei were
      similar to that in the locus coeruleus. [3H]nisoxetine binding was unevenly
      distributed along the entire rostral-caudal extent of the dorsal raphe, with the
      highest binding occurring in the interfascicular and ventral nuclei. A moderate
      amount of [3H]nisoxetine binding was also observed in the median raphe nucleus.
      The specificity of [3H]nisoxetine binding to NETs in monoaminergic nuclei was
      assessed by measuring the inhibition of its binding by desipramine, imipramine,
      or citalopram. The order of affinities of these drugs was identical in the locus
      coeruleus and dorsal and median raphe and was characteristic of binding to NETs
      (desipramine > imipramine > citalopram). Thus, high levels of NETs and an uneven
      distribution of NETs occur in the locus coeruleus as well as in the dorsal raphe
      nuclei of the human.

PMID- 9030631
TI  - Spatially selective auditory responses in the superior colliculus of the
      echolocating bat.
AB  - When a bat approaches a target, it continuously modifies its echolocation sounds
      and relies on incoming echo information to shape the characteristics of its
      subsequent sonar cries. In addition, acoustic information about the azimuth and
      elevation of a sonar target elicits orienting movements of the head and pinnae
      toward the sound source. This requires a common sensorimotor interface, where
      echo information is used to guide motor behaviors. Using single-unit
      neurophysiological methods and free-field auditory stimulation, we present data
      on biologically relevant specializations in the superior colliculus (SC) of the
      bat for orientation by sonar. In the bat's SC, two classes of spatially tuned
      neurons are distinguished by their sensitivity to echoes. One population shows
      facilitated, delay-tuned responses to pairs of sounds, simulating sonar emissions
      and echoes. Delay tuning, related to encoding target range, may play a role in
      guiding motor responses in echolocation, because the bat adjusts its emissions
      with changes in target distance. The delay-facilitated response depends on the
      direction of stimulation and on the temporal relationship between the simulated
      emission and echo in the sound pair, suggesting that this class of neurons
      represents the location of a target in three dimensions. A second population
      encodes the target in two dimensions, azimuth and elevation, and does not show a
      facilitated response to echoes delivered from any locus. Encoding of azimuth and
      elevation may be important for directing head aim, and this class may function in
      transforming auditory spatial information into signals used to guide acoustic
      orientation.

PMID- 9030632
TI  - Tension distribution of single motor units in multitendoned muscles: comparison
      of a homologous digit muscle in cats and monkeys.
AB  - To determine whether single motor units (MUs) in multitendoned muscles distribute
      tension to multiple tendons or instead focus tension selectively on a single
      tendon, we examined the distribution of tension generated by single MUs in the
      cat extensor digitorum lateralis (EDLat), and in its macaque homolog, the
      extensor digiti quarti et quinti (ED45). General properties of MUs (maximal
      tetanic tension, axonal conduction velocity, and twitch rise time) were similar
      in these muscles to those reported for other limb muscles in cats and monkeys.
      Most cat EDLat MUs were found to exert tension rather selectively on one of the
      three tendons of the muscle. Fast fatigable MUs were slightly but significantly
      more selective than fast fatigue-resistant and slow MUs. In contrast, and
      contrary to expectation, the macaque ED45 contained a lower proportion of MUs
      that exerted tension selectively on one of the two tendons of the muscle, and a
      higher proportion of relatively nonselective MUs. These findings suggest that the
      cat EDLat may consist of three functional subdivisions, each acting
      preferentially on a different tendon, whereas the macaque ED45 is more likely to
      function as a single multitendoned muscle.

PMID- 9030633
TI  - Modulation of oscillator interactions in the crab stomatogastric ganglion by
      crustacean cardioactive peptide.
AB  - The modulation of the pyloric rhythm of the stomatogastric ganglion of the crab,
      Cancer borealis, by crustacean cardioactive peptide (CCAP) is described. CCAP
      activated pyloric rhythms in most silent preparations, and altered the phase
      relationships of pyloric motor neuron firing in all preparations. In CCAP, the
      pyloric rhythms were characterized by long lateral pyloric (LP) neuron bursts of
      action potentials. The threshold for CCAP action was approximately 10(-10) M,
      with increasing effects at higher CCAP concentrations. The changes in motor
      pattern evoked by CCAP produced significant changes in LP-innervated muscle
      movement. These movements were additionally potentiated by CCAP applications to
      isolated nerve-muscle preparations. Thus, enhanced motor neuron firing and
      increase of the gain of the neuromuscular junctions are likely to operate
      coordinately in response to hormonally released CCAP. High CCAP concentrations
      sometimes resulted in modification of the normal 1:1 alternation between the
      pyloric dilator (PD) and LP neurons to patterns of 2:1, 3:1, or 4:1 alternation.
      CCAP seems to activate slow intrinsic oscillations in the LP neuron, as well as
      enhance faster oscillations in the pacemaker group of PD/anterior burster (AB)
      neurons. Simulations of fast and slow oscillators with reciprocal inhibitory
      coupling suggest mechanisms that could account for the mode switch from 1:1
      alternation to multiple PD bursts alternating with one LP neuron burst.

PMID- 9030634
TI  - Representation of accurate temporal information in the electrosensory system of
      the African electric fish, Gymnarchus niloticus.
AB  - Differential-phase-sensitive neurons in the electrosensory lateral line lobe
      (ELL) of the African electric fish, Gymnarchus niloticus, are sensitive to time
      disparities on the order of microseconds between afferent action potentials.
      These action potentials fire in a phase-locked manner in response to the animal's
      own wave-type electric organ discharges (EODs) (). The time disparity is one of
      the essential cues for an electrical behavior, the jamming avoidance response
      (JAR). To gain an insight into the accurate temporal processing in the ELL,
      firing time accuracy and dynamic response properties of action potentials of the
      phase-locked neurons (PLNs) in the ELL were examined. The temporal accuracy of
      the entire neuronal circuit for the JAR was also measured using behavioral
      responses. Standard deviation of firing times of PLNs' action potentials was
      approximately 6 micro;sec. The PLNs represent zerocrossing times of each stimulus
      cycle with this accuracy even when stimulus phase was modulated at high
      frequencies ( approximately 50 Hz). Distinct JAR occurred when time disparity was
      diminished below 1 micro;sec, and a marginal JAR could still be detected with a
      time disparity of 100 nsec. Standard deviation of the firing times of EODs was
      approximately several hundred nanoseconds. This stability of the EOD, however,
      was demonstrated to be unnecessary for the JAR. JARs occurred even when a large
      artificial jitter ( approximately 60 micro;sec) was introduced to a stimulus that
      mimicked fish's own EOD and the time disparity for JAR was diminished to 1
      micro;sec. This immunity of JAR to the EOD jitter is explained by the
      insensitivity of the differential-phase-sensitive neurons in the ELL to a common
      phase modulation. The JAR of the South American electric fish, Eigenmannia, also
      occurs in response to stimuli that generate comparably small phase differences (;
      ). The present study revealed that the independently evolved Eigenmannia and
      Gymnarchus exhibit a comparative level of remarkable temporal accuracy.

PMID- 9030635
TI  - Phencyclidine increases forebrain monoamine metabolism in rats and monkeys:
      modulation by the isomers of HA966.
AB  - The noncompetitive NMDA receptor antagonist phencyclidine (PCP) has
      psychotomimetic properties in humans and activates the frontal cortical dopamine
      innervation in rats, findings that have contributed to a hyperdopaminergic
      hypothesis of schizophrenia. In the present studies, the effects of the
      enantiomers of 3-amino-1-hydroxypyrrolid-2-one (HA966) on PCP-induced changes in
      monoamine metabolism in the forebrain of rats and monkeys were examined, because
      HA966 has been shown previously to attenuate stress- or drug-induced activation
      of dopamine systems. In rats, PCP (10 mg/kg, i.p.) potently activated dopamine
      (DA) turnover in the medial prefrontal cortex (PFC) and nucleus accumbens.
      Serotonin utilization was also increased in PFC. Pretreatment with either R
      (+)HA966 (15 mg/kg, i.p.) or S-(-)HA966 (3 mg/kg, i.p.) partially blocked PCP
      induced increases in PFC DA turnover, whereas neither enantiomer altered the
      effect of PCP on DA turnover in the nucleus accumbens or the PCP-induced
      increases in serotonin turnover in PFC. PCP (0.3 mg/kg, i.m.) exerted regionally
      selective effects on the dopaminergic and serotonergic innervation of the monkey
      frontal cortex, effects blocked by pretreatment with S-(-)HA966 (3 mg/kg, i. m.).
      Importantly, these data demonstrate that in the primate, PCP has potent effects
      on dopamine transmission in the frontal cortex, a brain region thought to be
      dysfunctional in schizophrenia. In addition, a role for S-(-)HA966 as a modulator
      of cortical monoamine transmission in primates is posited.

PMID- 9030636
TI  - Phosphorylation of transcription factor CREB in rat spinal cord after formalin
      induced hyperalgesia: relationship to c-fos induction.
AB  - The involvement of cAMP-responsive element-binding protein (CREB) signaling in
      tissue injury-induced inflammation and hyperalgesia has been characterized by
      measuring phosphorylation of CREB at serine-133 (CREB Ser133) using a specific
      antibody. In the unstimulated state, unphosphorylated CREB was observed in most
      nuclei of spinal neurons except for motor neurons, where only a small portion of
      neurons were stained. A few dorsal root ganglion (DRG) neurons were also CREB
      positive. After a unilateral injection of formalin into the hindpaw, a strong and
      bilateral phosphorylation of CREB Ser133 was induced, as assessed by both
      immunohistochemistry and Western blot. PhosphoCREB (pCREB)-positive neurons were
      found in laminae I, II, V, and X of spinal cord on both sides. CREB
      phosphorylation was very rapid and reached peak levels within 10 min of formalin
      treatment, whereas few pCREB-positive neurons were seen in unstimulated spinal
      cord. The induction of pCREB was predominantly postsynaptic, because only 5% of
      DRG neurons were labeled after inflammation. In contrast to CREB phosphorylation,
      the induction of c-Fos expression reached peak levels 2 hr after formalin
      treatment and c-Fos induction was mainly ipsilateral. Both formalin-evoked CREB
      phosphorylation and c-Fos expression in the spinal cord were suppressed by
      pretreatment with the NMDA receptor antagonist MK-801 (3.5 mg/kg, i.p.) or
      halothane anesthesia. These results suggest that CREB signaling may play a role
      in the long-term facilitation of spinal cord neurons after hyperalgesia.
      Furthermore, our results indicate that CREB phosphorylation may be necessary but
      not sufficient for c-fos induction.

PMID- 9030637
TI  - 5-HT inhibits calcium current and synaptic transmission from sensory neurons in
      lamprey.
AB  - In the lamprey spinal cord, 5-hydroxytryptamine (5-HT) immunoreactivity (ir) is
      present in the ventromedial plexus originating from intraspinal neurons,
      ventrolateral column arising from the brainstem, and dorsal column. The latter 5
      HT system originates from small dorsal root ganglion neurons. Combined Lucifer
      yellow intracellular labeling of the intraspinal sensory neurons, dorsal cells,
      and 5-HT immunohistochemistry showed close appositions between 5-HT-ir fibers and
      dorsal cell axons. Application of 5-HT depressed monosynaptic EPSPs evoked in
      giant interneurons by stimulation of single dorsal cells, dorsal roots, or dorsal
      column without any detectable change in the input resistance of postsynaptic
      neurons. Furthermore, the amplitude of AMPA-evoked depolarizations in giant
      interneurons was unaffected by 5-HT. The lack of postsynaptic effects of 5-HT
      indicates that the decrease of the amplitude of sensory monosynaptic EPSPs by 5
      HT is mediated by presynaptic mechanisms. The inhibition of monosynaptic EPSPs by
      5-HT was not counteracted by an antagonist of 5-HT1A receptors. 5-HT also reduced
      the amplitude of the calcium current recorded in isolated dorsal cells and slowed
      down its kinetics. The inhibition of calcium channels could represent the
      mechanism mediating the depression of synaptic transmission at the axonal level.
      These results show that activation of 5-HT receptors on dorsal cell axons as well
      as on other sensory neurons mediates inhibition of sensory synaptic transmission
      to giant interneurons. In intact animals, 5-HT could be released from small 5-HT
      neurons in dorsal root ganglia, which thus may underlie direct sensory-sensory
      interactions.

PMID- 9030638
TI  - Differential binding profile and internalization process of neurotensin via
      neuronal and glial receptors.
AB  - Two G-protein-coupled receptors for the tridecapeptide neurotensin (NT) have been
      identified and cloned in mammalian brain: a high-affinity (Kd = 0.3 nM) receptor,
      sensitive to the antagonist SR 48692 but insensitive to levocabastine, and a
      lower-affinity (Kd = 2-4 nM) receptor, sensitive to levocabastine but with poor
      affinity for SR 48692. Although there is good evidence that the high-affinity
      site is predominantly expressed in neurons, little is known of the cellular
      localization of the low-affinity receptor. In the present study, we identify by
      confocal microscopy selective levocabastine-sensitive, SR 48692-resistant binding
      of a fluorescent derivative of NT (fluo-NT) to a subpopulation of glial
      fibrillary acidic protein-immunoreactive glial cells grown in culture from the
      midbrain and cerebral cortex of embryonic and neonatal rats, respectively. We
      also demonstrate, by combining fluo-NT detection with tyrosine hydroxylase
      immunofluorescence, that these glial binding sites are differentially regulated
      from the SR 48692-sensitive NT receptor expressed in the same cultures by
      mesencephalic dopamine neurons. Whereas the latter undergoes rapid ligand-induced
      internalization followed by centripetal mobilization of ligand-receptor complexes
      from processes to perikarya and from perikaryal periphery to cell center, the
      former induces the formation of cell-surface clusters that fail to internalize.
      It is concluded that NT may exert its effects on both neurons and astrocytes in
      the CNS. Whereas NT neural signaling is exerted through high-affinity receptors
      and may be partly effected through internalization of receptor-ligand complexes,
      glial signaling is exerted through low-affinity NT receptors and appears to be
      transduced exclusively at the level of the plasma membrane.

PMID- 9030639
TI  - Loss of lever press-related firing of rat striatal forelimb neurons after
      repeated sessions in a lever pressing task.
AB  - Lateral striatal neurons that fire phasically in relation to active movement of
      the contralateral forelimb (determined via daily sensorimotor examination) were
      studied during acquisition of cued lever pressing. Rats were trained to lift the
      contralateral forepaw from the floor to press a lever in the presence of a tone.
      The tone was presented 70 times per day (session) for 18 consecutive days. All
      animals acquired the task, evidenced by gradual improvements across sessions and
      eventual asymptotic levels in tone discrimination, reaction time, and efficiency
      of the lever press. Forelimb neurons fired in relation to the lever press during
      early sessions of acquisition but not after repeated sessions on the task. This
      difference in firing could not be attributed to differences in forelimb movements
      during lever pressing or to sampling from different populations of neurons in
      early versus late sessions. In view of evidence that striatal damage impairs
      acquisition of motor skills, the change in firing suggests that the striatal
      activity present in early sessions may be necessary for the acquisition of, but
      not the automatic performance of, learned motor responses.

PMID- 9030640
TI  - Effects of interaural intensity difference on the processing of interaural time
      difference in the owl's nucleus laminaris.
AB  - Interaural time and intensity differences (ITD and IID) are processed
      independently in the owl's auditory system. This paper examines whether this
      independence is established in nucleus laminaris (NL), the first site of ITD
      processing. A plot of discharge rate against time difference (ITD curve) is
      sinusoidal in NL. The ITDs that produce the peaks are called the most favorable
      ITDs, and those that produce the troughs are called the least favorable ITDs. IID
      had little effect on the discharge rates of laminaris neurons for the most and
      least favorable ITDs. The degree of peak-trough modulation changed slightly with
      variation in IID. In contrast, IID in tonal stimuli affected the temporal aspect
      of ITD curves depending on the difference between the stimulus frequency and the
      neuron's best frequency (BF). For frequencies below BF, IID caused large and
      systematic shifts in ITD toward the ear in which the sound was louder, whereas
      for frequencies above BF, IID caused small shifts in ITD toward the opposite ear.
      IID had little effect on ITD curves taken with BF or broadband noise. These
      results can be largely accounted for by the effects of frequency and intensity on
      the timing of impulses at the level of the cochlear nuclei. Thus, the processing
      of ITD by NL neurons is independent of IID for behaviorally relevant stimuli,
      because the timing of impulses is insensitive to sound level when the signal is
      broadband.

PMID- 9030641
TI  - Metabotropic glutamate receptor activation modulates kainate and serotonin
      calcium response in astrocytes.
AB  - Although metabotropic glutamate receptor (mGluR) modulation has been studied
      extensively in neurons, it has not been investigated in astrocytes. We studied
      modulation of glutamate-evoked calcium rises in primary astrocyte cultures using
      fura-2 ratiometric digital calcium imaging. Calcium plays a key role as a second
      messenger system in astrocytes, both in regulation of many subcellular processes
      and in long distance intercellular signaling. Suprachiasmatic nucleus (SCN) and
      cortical astrocytes showed striking differences in sensitivity to glutamate and
      to mGluR agonists, even after several weeks in culture. Kainate-evoked
      intracellular calcium rises were inhibited by concurrent application of the type
      I and II mGluR agonists quisqualate (10 micro;M), trans-(+/-)-1-amino-1,3
      cyclopentanedicarboxylate (100-500 micro;M), and (2S-1'S-2'S)-2
      (carboxycyclopropyl)glycine (L-CCG-I) (10 micro;M). Inhibition mediated by L-CCG
      I had long-lasting effects (>45 min) in approximately 30% of the SCN astrocytes
      tested. The inhibition could be mimicked by the L-type calcium channel blocker
      nimodipine (1 micro;M) as well as by protein kinase C (PKC) activators phorbol
      12,13-dibutyrate (10 micro;M) and phorbol 12-myristate 13-acetate (500 nM), and
      blocked by the PKC inactivator (+/-)-1-(5-isoquinolinesulfonyl)-2
      methylpiperazine (200 micro;M), suggesting a mechanism involving PKC modulation
      of L-type calcium channels. In contrast, mGluRs modulated serotonin (5HT)-evoked
      calcium rises through a different mechanism. The type III mGluR agonist L-2-amino
      4-phosphonobutyrate consistently inhibited 5HT-evoked calcium rises, whereas in a
      smaller number of cells quisqualate and L-CCG-I showed both inhibitory and
      additive effects. Unlike the mGluR-kainate interaction, which required a
      pretreatment with an mGluR agonist and was insensitive to pertussis toxin (PTx),
      the mGluR modulation of 5HT actions was rapid and was blocked by PTx. These data
      suggest that glutamate, acting at several metabotropic receptors expressed by
      astrocytes, could modulate glial activity evoked by neurotransmitters and thereby
      influence the ongoing modulation of neurons by astrocytes.

PMID- 9030643
TI  - Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA
      receptor-mediated synaptic input: correlation with dendritic spine density.
AB  - Previous studies have shown that estradiol induces new dendritic spines and
      synapses on hippocampal CA1 pyramidal cells. We have assessed the consequences of
      estradiol-induced dendritic spines on CA1 pyramidal cell intrinsic and synaptic
      electrophysiological properties. Hippocampal slices were prepared from
      ovariectomized rats treated with either estradiol or oil vehicle. CA1 pyramidal
      cells were recorded and injected with biocytin to visualize spines. The
      association of dendritic spine density and electrophysiological parameters for
      each cell was then tested using linear regression analysis. We found a negative
      relationship between spine density and input resistance; however, no other
      intrinsic property measured was significantly associated with dendritic spine
      density. Glutamate receptor autoradiography demonstrated an estradiol-induced
      increase in binding to NMDA, but not AMPA, receptors. We then used input/output
      (I/O) curves (EPSP slope vs stimulus intensity) to determine whether the
      sensitivity of CA1 pyramidal cells to synaptic input is correlated with dendritic
      spine density. Consistent with the lack of an estradiol effect on AMPA receptor
      binding, we observed no relationship between the slope of an I/O curve generated
      under standard recording conditions, in which the AMPA receptor dominates the
      EPSP, and spine density. However, recording the pharmacologically isolated NMDA
      receptor-mediated component of the EPSP revealed a significant correlation
      between I/O slope and spine density. These results indicate that, in parallel
      with estradiol-induced increases in spine/synapse density and NMDA receptor
      binding, estradiol treatment increases sensitivity of CA1 pyramidal cells to NMDA
      receptor-mediated synaptic input; further, sensitivity to NMDA receptor-mediated
      synaptic input is well correlated with dendritic spine density.

PMID- 9030644
TI  - A test of the excitability-gradient hypothesis in the swimmeret system of
      crayfish.
AB  - The motor pattern that drives coordinated movements of swimmerets in different
      segments during forward swimming characteristically begins with a power-stroke by
      the most posterior limbs, followed progressively by power-strokes of each of the
      more anterior limbs. To explain this caudal-to-rostral progression, the
      hypothesis was proposed that the neurons that drive the most posterior swimmerets
      are more excitable than their more anterior counterparts, and so reach threshold
      first. To test this excitability-gradient hypothesis, I used carbachol to excite
      expression of the swimmeret motor pattern and used tetrodotoxin (TTX), sucrose
      solutions, and cutting to block the flow of information between anterior and
      posterior segments. I showed that the swimmeret activity elicited by carbachol is
      like that produced when the swimmeret system is spontaneously active and that
      blocking an intersegmental connective uncoupled swimmeret activity on opposite
      sides of the block. When anterior and posterior segments were isolated from each
      other, the frequencies of the motor patterns expressed by anterior segments were
      not slower than those expressed by posterior segments exposed to the same
      concentrations of carbachol. This result was independent of the concentration of
      carbachol applied and of the number of segmental ganglia that remained connected.
      When TTX was used to block information flow, the motor patterns produced in
      segments anterior to the block were significantly faster than those from segments
      posterior to the block. These observations contradict the predictions of the
      excitability-gradient hypothesis and lead to the conclusion that the hypothesis
      is incorrect.

PMID- 9030642
TI  - Activation of amygdala cholecystokininB receptors potentiates the acoustic
      startle response in the rat.
AB  - The acoustic startle reflex is a sensitive index of "anxiety" and "fear."
      Potentiation of startle by conditioned and unconditioned fear stimuli appears to
      be mediated by the amygdala. CholecystokininB (CCKB) agonists increase "anxiety"
      in laboratory animals and induce "panic" in humans. Here, we investigate the role
      CCKB receptor-mediated mechanisms in the amygdala in the potentiation of startle.
      First, intra-amygdala infusions of the CCKB receptor agonist pentagastrin (0,
      0.01, 0.1, 1, and 10 nM) produced a dose-related potentiation of acoustic startle
      responses. At the highest dose, startle amplitudes were increased up to 90% above
      preinfusion baseline levels. Second, similar infusions of pentagastrin had no
      effect on locomotor activity over the same time course, showing that increases in
      startle responsivity after infusions of pentagastrin are not attributable to
      nonspecific changes in motor activity. Third, infusions of similar doses of
      pentagastrin into the striatum or nucleus accumbens did not potentiate startle
      responses. Fourth, pretreatment with the CCKB receptor antagonist L-365,260 (0.1
      mg/kg, i.p.) attenuated the potentiation of startle produced by intra-amygdala
      infusions of pentagastrin. Finally, intra-amygdala infusion of the CCKB receptor
      selective antagonist PD-135158 (10 micro;g) blocked the potentiation of startle
      produced by i.c.v. infusions of pentagastrin, suggesting that i.c.v. infusions of
      pentagastrin potentiate startle responses via activation of amygdala CCKB
      receptors. These results show that amygdala CCKB receptor-mediated mechanisms are
      involved in the potentiation of acoustic startle responses.

PMID- 9030645
TI  - Sleep and sleep regulation in normal and prion protein-deficient mice.
AB  - Mice are the preferred mammalian species for genetic investigations of the role
      of proteins. The normal function of the prion protein (PrP) is unknown, although
      it plays a major role in the prion diseases, including fatal familial insomnia.
      We investigated its role in sleep and sleep regulation by comparing baseline
      recordings and the effects of sleep deprivation in PrP knockout mice (129/SV) and
      wild-type controls (129/SV x C57BL/6), which are the mice used for most gene
      targeting experiments and whose behavior is not well characterized. Although no
      difference was evident in the amount of vigilance states, the null mice exhibited
      a larger degree of sleep fragmentation than the wild-type with almost double the
      amount of short waking episodes. As in other rodents, cortical temperature
      closely reflected the time course of waking. The increase of slow-wave activity
      (SWA; mean EEG power density in the 0.25-4.0 Hz range) at waking to nonrapid eye
      movement (NREM) sleep transitions was faster and reached a lower level in the
      null mice than in the wild-type. The contribution of the lower frequencies (0.25
      5.0 Hz) to the spectrum was smaller than in other rodents in all three vigilance
      states, and the distinction between NREM sleep and REM sleep was most marked in
      the theta band. After the sleep deprivation, SWA was increased, but the changes
      in EEG power density and SWA were more prominent and lasted longer in the PrP
      null mice. Our results suggest that PrP plays a role in promoting sleep
      continuity.

PMID- 9030646
TI  - Selective roles for hippocampal, prefrontal cortical, and ventral striatal
      circuits in radial-arm maze tasks with or without a delay.
AB  - The hippocampus, the prefrontal cortex, and the ventral striatum form
      interconnected neural circuits that may underlie aspects of spatial cognition and
      memory. In the present series of experiments, we investigated functional
      interactions between these areas in rats during the performance of delayed and
      nondelayed spatially cued radial-arm maze tasks. The two-phase delayed task
      consisted of a training phase that provided rats with information about where
      food would be located on the maze 30 min later during a test phase. The single
      phase nondelayed task was identical to the test phase of the delayed task, but in
      the absence of a training phase rats lacked previous knowledge of the location of
      food on the maze. Transient inactivation of the ventral CA1/subiculum (vSub) by a
      bilateral injection of lidocaine disrupted performance on both tasks. Lidocaine
      injections into the vSub on one side of the brain and the prefrontal cortex on
      the other transiently disconnected these two brain regions and significantly
      impaired foraging during the delayed task but not the nondelayed task. Transient
      disconnections between the vSub and the nucleus accumbens produced the opposite
      effect, disrupting foraging during the nondelayed task but not during the delayed
      task. These data suggest that serial transmission of information between the vSub
      and the prefrontal cortex is required when trial-unique, short-term memory is
      used to guide prospective search behavior. In contrast, exploratory goal-directed
      locomotion in a novel situation not requiring previously acquired information
      about the location of food is dependent on serial transmission between the
      hippocampus and the nucleus accumbens. These results indicate that different
      aspects of spatially mediated behavior are subserved by separate, distributed
      limbic-cortical-striatal networks.

PMID- 9030647
TI  - Special considerations for the pediatric perioperative patient. A developmental
      approach.
AB  - Children are not just small adults. They have unique differences and needs both
      physiologically and psychosocially. The pediatric perioperative nurse is
      challenged to meet these needs by incorporating a knowledge of growth and
      development in all aspects of the plan of care.

PMID- 9030648
TI  - Pediatric sedation. Essentials for the perioperative nurse.
AB  - Sedation of children undergoing surgical procedures is one of many issues facing
      perioperative nurses today. This article reviews relevant professional guidelines
      for the practice of sedation in children and describes the implications for
      perioperative nurses. Topics covered include preparation of the patient,
      monitoring guidelines, and the use of pharmacological agents.

PMID- 9030649
TI  - Perioperative pain management in children.
AB  - In this article the authors review the developmental pathophysiology of pain and
      its effects on children. Assessment modalities for differing developmental levels
      in the pediatric patient are reviewed. Medical modalities including medications
      administered orally, patient-controlled analgesia, epidurals, and preemptive
      analgesia are described.

PMID- 9030650
TI  - Advances in pediatric anesthesia.
AB  - Advances in many aspects of pediatric anesthesia have resulted in a significant
      reduction in morbidity and mortality in children. Research and development have
      created vast improvements in pharmacology. Sophisticated monitoring and
      improvements in equipment evolved from advances made in scientific technology.
      Recognition of the psychological needs of children of all ages likely has reduced
      the incidence of lasting psychological effects after hospitalization. Finally,
      these important advances have made pediatric anesthesia a safer and more
      compassionate specialty.

PMID- 9030651
TI  - Current practices and advances in pediatric neurosurgery.
AB  - Advances in the field of neuroscience are enhancing outcomes for pediatric
      neurosurgical patients. Innovative diagnostic tools that include ventriculoscopy
      for hydrocephalus; long-term monitoring with subdural and epidural electrodes for
      seizures; and intraoperative computer-assisted, three-dimensional imaging for
      tumors are currently aiding neurosurgeons. These advances in the care of
      pediatric patients require the perioperative nurse to reevaluate and expand the
      nurse's role to optimize patient outcomes.

PMID- 9030652
TI  - Cochlear implantation in children.
AB  - Cochlear implantation in the pediatric population is no longer considered
      experimental practice since the Food and Drug Administration (FDA) approved the
      Nucleus 22 Channel cochlear implant in 1990. Today, cochlear implantation is a
      viable option for selected children with profound hearing loss to achieve
      potential language development. Not every child is a candidate, however, nor can
      implantation rectify the underlying cause of deafness or restore normal hearing
      function. For successful outcomes in proper candidates, rigorous pre-surgical
      evaluation and screening followed by long-term rehabilitation and education are
      necessary for both child and family. The close collaboration of an
      interdisciplinary team is essential throughout the process.

PMID- 9030653
TI  - Lasers in pediatric surgery.
AB  - Lasers, once a laboratory curiosity, have quickly become a viable and valuable
      surgical instrument. They have been found useful in almost every surgical
      specialty. This chapter will discuss how laser light is produced and its effects
      on tissue. The various laser types are discussed, and their clinical implications
      are reviewed. Most important, we also review the hazards associated with these
      systems and the ramifications of their use. The perioperative nurse must be
      familiar with the various protocols used in treating patients with lasers,
      applications of the lasers, and specific safety requirements.

PMID- 9030654
TI  - Extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation (ECMO) is prolonged cardiopulmonary bypass
      used to treat critically ill patients with severe but reversible cardiac and/or
      respiratory failure. The severity of their symptoms, the rapid deterioration in
      their conditions, the difficulty in mechanical transportation, and the risks of
      traveling with an ECMO circuit often prohibit cannulation in an operating room.
      Cannulation for and decannulation after ECMO therapy can be safely accomplished
      in the intensive care unit by utilizing experienced perioperative nurses.

PMID- 9030655
TI  - Streamlining the perioperative process.
AB  - Health-care reform and capitated reimbursements have and will continue to
      influence decreased lengths of hospital stay and continued efficiency in
      perioperative nursing practice. Collaborative efforts by perioperative nurses,
      anesthesia care providers, and surgical staff should continue to emphasize
      concise documentation processes as well as comprehensive assessment and
      evaluation phases to prepare patients and families for earlier discharge and
      recovery at home. The objective of new documentation practices and streamlining
      perioperative preparation processes is to eliminate the duplication of
      information, meet standards set by professional organizations, and provide
      quality, efficient care along with patient and family satisfaction.

PMID- 9030657
TI  - Latex allergy. Considerations for the care of pediatric patients and employee
      safety.
AB  - Certain groups of patients and health care workers are at high risk for
      developing latex allergy. In the perioperative arena, there is an increased risk
      for this allergy due to the mode and frequency of latex exposure. Using a
      multidisciplinary team approach, nurses must institute policies and procedures
      for precautions to take with latex to ensure that patients and employees remain
      in a safe environment. Through education, research and collaboration with
      industry and health care professionals, latex sensitization can be minimized, and
      latex allergic reactions avoided.

PMID- 9030656
TI  - Ethical issues in pediatric perioperative nursing.
AB  - Pediatric perioperative nurses often face ethical issues in their daily practice.
      Some of these issues require the ability to make a quick decision. Resources and
      mechanisms nurses can use to gain the knowledge required for ethical decision
      making are to attend ethical, legal, and clinical conferences, read ethical
      articles in nursing, medical, legal and ethical journals, and discuss issues with
      colleagues. Consultation can be obtained through ethics advisory committees and
      ethicists or people knowledgeable about ethics. Nurses must be able to identify
      ethical issues and how ethical decisions are made in order to analyze arguments
      critically, reflect on decisions, and examine positions. Nurses must have the
      ability to acknowledge and identify a conflict that exists between personal and
      professional values and to attempt to resolve the conflict. Perioperative nurses
      need to accept responsibility for their actions and take reactions based on
      ethical reasoning when providing patient care. By being knowledgeable of ethical
      issues and how to address them, pediatric perioperative nurses are better
      prepared to provide comprehensive nursing care to all patients and families.

PMID- 9030658
TI  - An approach to pediatric perioperative care. Parent-present induction.
AB  - Allowing a parent to be present for the induction of mask anesthesia may minimize
      the stressors of separation experienced by pediatric patients undergoing a
      surgical procedure. A parent-present anesthesia induction program has been
      implemented at Children's Hospital in Boston in response to issues which have
      been voiced by parents and staff members, regarding separation and emotional
      trauma. Patient and parent selection are important variables to a successful
      program. Preparation of the parent for parent-present anesthesia induction is
      evaluated by an ongoing quality improvement survey.

PMID- 9030659
TI  - Unlicensed assistive personnel in the perioperative setting.
AB  - The present climate in health care, including a tendency toward more managed care
      and capitation systems, has caused hospital administrators and perioperative
      managers to reexamine traditional work systems and their associated costs. Some
      decisions around work redesign may be financially driven or based on the
      decreased availability of qualified professionals in the job market. The use of
      an increased number of unlicensed assistive personnel (UAP) in hospital settings
      has become a common redesign strategy to address both issues. In the
      perioperative setting, some traditional roles are well established for UAP.
      Today, changes associated with downsizing, cost containment, and increasing
      technology have opened up new opportunities to explore ways to integrate UAP
      roles into the perioperative setting.

PMID- 9030660
TI  - Interdisciplinary quality improvement in the perioperative program. A
      collaborative model.
AB  - The practice at Children's Hospital has demonstrated the many benefits of the
      collaborative method of TQM. It allows the various disciplines to share their
      perspectives on patient care with other members of the health-care team. This
      broadens each person's perspective and generates respect for the work of others
      in achieving high levels of patient care. An effective committee empowers by
      providing a way for every employee to feel that his or her voice can be heard and
      that legitimate issues of quality of care, cost reduction, and system efficiency
      will be explored when identified.

PMID- 9030662
TI  - Fasciola hepatica: detection of antigenemia and coproantigens in experimentally
      infected rats.

PMID- 9030661
TI  - Heterologous protection by Leishmania donovani for Leishmania major infections in
      the vervet monkey model of the disease.
AB  - The study was aimed at analyzing immunological cross-reactivity between
      Leishmania major and Leishmania donovani and possible cross-protection between
      the two parasite species in the vervet monkey model of the disease. Nine vervet
      monkeys (Cercopithecus aethiops) from the institute animal colony were sued in
      the study. Five of the animals had been previously infected with L. donovani but
      had remained asymptomatic while the other four animals were naive and comprised
      the control group. Immunological responses to both L. major and L. donovani
      antigens in the five animals with prior exposure to L. donovani were examined
      before challenge. High antibody titers to the two antigens were demonstrated in
      an enzyme-linked immunosorbent assay, but the antibody titers to L. donovani were
      significantly higher than those to L. major (P < 0.005). Positive in vitro
      peripheral blood leucocyte (PBL) proliferation to L. major and L. donovani
      antigens was also demonstrated, but there was no significant difference in the
      response to the two antigens (P > 0.1). High and varying levels of interferon
      gamma (IFN-gamma) were secreted in PBL from the five vervet monkeys when
      stimulated with L. major antigen, but vervet monkey 1296 secreted marginal levels
      of IFN-gamma. When the animals were challenged intradermally with 1 x 10(5)
      virulent L. major promastigotes mixed with sandfly vector salivary gland lysate
      all four vervet monkeys in the control group developed nodules of varying sizes
      at the inoculation sites that eventually ulcerated. However, nodule formation and
      ulceration occurred at different times among these animals. The other five
      animals (animals with prior exposure to L. donovani) did not pick up the
      infection at all, but one animal from this group, vervet monkey 1296, developed a
      transient lesion that healed within 9 weeks, the same animal that had been shown
      to secrete low levels of IFN-gamma. The results demonstrate high cross-reactivity
      between L. donovani and L. major and that L. donovani protects against L. major
      infections. This finding is important for vaccine development studies against
      leishmaniasis.

PMID- 9030663
TI  - Plasmodium falciparum: an epitope within a highly conserved region of the 47-kDa
      amino-terminal domain of the serine repeat antigen is a target of parasite
      inhibitory antibodies.
AB  - Previously, the Plasmodium falciparum serine repeat antigen has been shown to be
      protective in primate models of malaria immunity and also to be a target of in
      vitro parasite-inhibitory antibodies. To further define parasite-inhibitory
      epitopes a series of deletions from the amino-terminal 47-kDa domain of the
      serine repeat antigen (SERA) were constructed as glutathione-S-transferase fusion
      proteins. Several GST-SERA fusion proteins were used to vaccinate mice with
      Freund's adjuvant and the resulting immune sera were used to assay for the
      inhibition of P. falciparum invasion of erythrocytes in vitro. The minimal
      epitope shown to be the target of invasion-blocking antibodies was SERA amino
      acids 17-165. Additional GST-SERA deletion constructs of the 47-kDa domain were
      developed and evaluated for reactivity, by Western immunoblot analysis, with a
      parasite-inhibitory murine monoclonal antibody (mAb 43E5), a parasite-inhibitory
      pooled goat polyclonal sera, and a pooled human Nigerian immune serum. The
      parasite-inhibitory epitope defined by mAb 43E5 was mapped to SERA amino acids 17
      110 and, at least, part of the epitope was defined to include amino acids in the
      region of amino acids 59-72. The parasite-inhibitory epitope recognized by mAb
      43E5 appears to be well conserved between diverse geographical isolates of P.
      falciparum. The results have relevance for malaria vaccine development and
      suggest that an appropriately designed recombinant SERA antigen produced from a
      synthetic gene in Escherichia coli may be an effective component of a candidate
      malaria vaccine.

PMID- 9030664
TI  - Plasmodium falciparum: altered expressions of erythrocyte membrane-associated
      antigens during antigenic variation.
AB  - The O and R antigenic variants of the Plasmodium falciparum Palo Alto strain
      present differences in the morphology of the infected red blood cell membrane, in
      their adhesion properties, surface immunofluorescence, and agglutination
      specificities and importantly, induce a variant-specific protection after a
      primary infection in Saimiri sciureus monkeys. To identify potential targets of
      variant-specific immunity, we have compared the antigenic makeup of both variants
      by immunoblot. O-specific monkey sera generated similar profiles on both parasite
      types, while R-specific sera showed a consistent difference on a high-molecular
      mass undefined antigen. Distinct antibody specificities were eluted from the
      surface of O- or R-infected erythrocytes, generating variant-specific
      agglutination, surface immunofluorescence, and immunoblot profiles. An antiserum
      raised to Pf60.1, predicted to cross-react with the cytoplasmic domain of PfEMP1,
      reacted with specific, SDS-soluble antigens in both variants. Antigens associated
      with the membrane of the infected red blood cells were further investigated using
      several specific antisera. The 85-kDa HRP1 gene product was more abundant in O
      than in R parasites, while the reverse was observed for the PfEMP3 protein. These
      data indicate that O and R parasites differ in the expression of several antigens
      associated with the membrane of the infected red blood cell.

PMID- 9030665
TI  - Leishmania mexicana: binding of promastigotes to type I collagen.
AB  - During leishmania infection, parasites are inoculated to the human host through
      the bite of a sandfly vector into the dermis, where they first interact with
      tissue components, cells and extracellular matrix molecules. Since collagen is
      the most abundant component of the skin matrix, we investigated whether there is
      a specific interaction of Leishmania mexicana promastigotes with this host
      component. Promastigotes were able to attach to collagen fibrils and move through
      the matrix of mouse skin sections and to penetrate easily into a type I collagen
      gel. Denatured type I collagen coated beads (Cytodex 3) readily bound to the
      parasite surface. The interaction of promastigotes with type I collagen was dose
      dependent and saturable and was competitively and specifically inhibited with
      increasing concentrations of gelatin. Biotin-labeled parasite surface molecules
      were able to associate with both denatured collagen from microcarriers and native
      type I collagen from bovine kidney. It is suggested that the presence of parasite
      cell membrane receptors to collagen may confer a specific tropism for the skin,
      where collagen is the most abundant component of the matrix.

PMID- 9030666
TI  - Hymenolepis diminuta: mitochondrial NADH --> NAD transhydrogenation and the
      lipoamide dehydrogenase system.
AB  - The occurrence of NADH --> NAD transhydrogenation and lipoamide dehydrogenase
      activities was demonstrated for cysticercoids of the intestinal cestode,
      Hymenolepis diminuta. In addition, both activities were catalyzed by the
      mitochondria of 6-, 10-, and 14-day H. diminuta and by the mitochondria from
      immature, mature, and pregravid/gravid regions of the adult cestode. A
      developmentally related increase in NADH --> NAD activity was suggested and the
      levels of both activities in the immature region of the helminth were consistent
      with it being a region of high metabolic activity. Adult H. diminuta
      mitochondrial lipoamide dehydrogenase was purified to homogeneity. The native
      enzyme was a homodimer with a monomeric and dimeric molecular mass of 47 and 93
      kDa, respectively. Spectral analyses revealed that the enzyme contained flavin.
      More importantly, the purified enzyme catalyzed appreciable NADH --> NAD
      transhydrogenation activity, a premier finding for the phylum Platyhelminthes.
      The ratio of NADH --> NAD transhydrogenation to lipoamide reduction was 1:5. Both
      activities were inhibited by Cu2+ and Cd2+ with the NADH --> NAD activity being
      more resistant to inhibition. Interestingly, aside from NADH diaphorase activity,
      the cestode enzyme displayed NADH-ferricyanide reductase and, to a lesser degree,
      NADPH --> NAD transhydrogenation activities. The partial amino acid sequence of
      H. diminuta lipoamide dehydrogenase indicated that this enzyme was most similar
      to the corresponding enzymes of other parasitic helminths. Moreover, the
      phenylalanine for leucine substitution found in the redox-active disulfide site
      of the lipoamide dehydrogenases of some anaerobic systems was noted for the H.
      diminuta enzyme.

PMID- 9030667
TI  - The malaria circumsporozoite protein: interaction of the conserved regions I and
      II-plus with heparin-like oligosaccharides in heparan sulfate.
AB  - The malaria circumsporozoite (CS) protein binds to glycosaminoglycans from
      heparan sulfate proteoglycans on the cell surface of hepatocytes and is
      specifically cleared from the bloodstream by the liver. We show here that the two
      conserved regions, I and II-plus, of the CS protein, in a concerted action,
      preferentially bind to highly sulfated heparin-like oligosaccharides in heparan
      sulfate. In a concentration-dependent manner, peptides representing region I and
      region II-plus inhibited the binding of recombinant CS protein to HepG2 cells by
      62 and 84%, respectively. Furthermore, the action of endoproteinase Arg-C, which
      cleaves the recombinant CS constructs CS27IVC and CSFZ(Cys) predominantly at the
      conserved region I, was inhibited by heparin in a concentration-dependent
      fashion. CSFZ(Cys), which has a higher affinity to HSPGs than CS27IVC, was
      stabilized by heparin at a w/w ratio (CS protein:glycosaminoglycan) of 20/1,
      whereas full protection of CS27IVC required more heparin (5/1). Heparan sulfate
      provided full protection of CSFZ(Cys) only at a ratio of 1/10. Native fucoidan as
      well as normally sulfated fuco-oligosaccharides (0.76 mol sulfate/mol fucose)
      inhibited Plasmodium berghei development in HepG2 cells by 84 and 66%,
      respectively, in a concentration-dependent manner and sporozoite invasion into
      CHO cells by 80%. Desulfated fucoidan oligosaccharides were inactive. These
      results may explain the selective interaction between the CS protein and the
      unique heparan sulfate from liver, which is noted for its unusually high degree
      of sulfation, and may provide a plausible explanation for the selective targeting
      of the malaria CS protein to the liver.

PMID- 9030668
TI  - Trypanosoma brucei brucei: a long-term model of human African trypanosomiasis in
      mice, meningo-encephalitis, astrocytosis, and neurological disorders.
AB  - The search for a chronic experimental model for human African trypanosomiasis
      (HAT) in animals with cerebral lesions and neurological disorders has been
      difficult. Models with meningo-encephalitis have been proposed using Trypanosoma
      brucei gambiense or T. b. rhodesiense. Meningo-encephalitis is rare in infection
      with T. b. brucei. It has been shown that the treatment of mice infected with T.
      b. brucei with diminazene aceturate (Berenyl) led to development of a rapid
      meningo-encephalitis. In this study, we report the development of a chronic
      experimental model of HAT in mice infected with T. b. brucei AnTat 1.1E. To
      obtain a chronic evolution of the infection, on Day 21 postinfection, mice were
      treated with a dose of suramin (Moranyl) at 20 mg x kg(-1) body weight, a dose
      which failed to eliminate trypanosomes in the central nervous system (CNS). This
      treatment, repeated after each parasitemic relapse in the blood, allowed animals
      to survive more than 300 days postinfection. After a few weeks of infection, mice
      displayed neurological signs. Histological studies showed the appearance of
      increasing inflammatory lesions, from meningitis to meningo-encephalitis, with
      progression of lesions throughout the perivascular spaces in cerebral and
      cerebellum parenchyma. No demyelination or neuronal alteration were observed
      except in the necrotic spaces. Trypanosomes were observed in different structures
      in CNS. An immunohistochemical study of glial fibrillary acidic protein (GFAP)
      showed an increasing astrocytosis according to the duration of the infection.
      This model reproduces neurological and histological pathology observed in the
      human disease and can be useful for further immunopathological, neurohistological
      and therapeutic studies on this condition.

PMID- 9030669
TI  - Sensitive and specific detection of Trypanosoma vivax using the polymerase chain
      reaction.
AB  - The nucleic acid probes that are currently in use detect and distinguish
      Trypanosoma vivax parasites according to their geographic origin. To eliminate
      the need for using multiple DNA probes, a study was conducted to evaluate the
      suitability of a tandemly reiterated sequence which encodes a T. vivax diagnostic
      antigen as a single probe for detection of this parasite. The antigen is
      recognized by monoclonal antibody Tv27 currently employed in antigen detection
      ELISA (Ag-ELISA). A genomic clone which contained a tetramer of the 832-bp cDNA
      sequence was isolated and shown to be more sensitive than the monomer.
      Oligonucleotide primers were designed based on the nucleotide sequence of the 832
      bp cDNA insert and used in amplifying DNA sequences from the blood of cattle
      infected with T. vivax isolates from West Africa, Kenya, and South America. The
      polymerase chain reaction (PCR) product of approximately 400 bp was obtained by
      amplification of DNA from all the isolates studied. The oligonucleotide primers
      also amplified DNA sequences in T. vivax-infected tsetse flies. Subsequently, PCR
      was evaluated for its capacity to detect T. vivax DNA in the blood of three
      animals experimentally infected with the parasite. T. vivax DNA was detectable in
      the blood of infected animals as early as 5 days post-infection. Blood and serum
      samples from the three cattle and from six other infected animals were also
      examined for the presence of trypanosomes and T. vivax-specific diagnostic
      antigen. Trypanosomes appeared in the blood 7-12 days post-challenge, while the
      antigenemia was evident on Days 5-20 of infection. Analysis of the data obtained
      in the three animals during the course of infection revealed that the buffy coat
      technique, Ag-ELISA, and PCR revealed infection in 42, 55, and 75% of the blood
      samples, respectively. PCR amplification of genomic DNA of T. vivax is thus
      superior to the Ag-ELISA in the detection of T. vivax. More importantly, both the
      T. vivax diagnostic antigen and the gene encoding it are detectable in all the T.
      vivax isolates examined from diverse areas of Africa and South America.

PMID- 9030670
TI  - The time course of selected malarial infections in cytokine-deficient mice.
AB  - Murine malarial parasites have long been characterized by their requirement for
      either antibody-mediated immunity (AMI) or cell-mediated immunity (CMI) for
      suppression of acute parasitemia, with Plasmodium yoelii reportedly requiring AMI
      for suppression and P. chabaudi requiring CMI. To assess this characterization in
      terms of the current T(H1)/T(H2)-CMI/AMI hypothesis, we infected gene-targeted
      "knockout" mice lacking either a type-1 cytokine (IL-2 or IFN-gamma) or a type-2
      cytokine (IL-4 or IL-10) with one or the other species of Plasmodium. We observed
      that type-1 cytokine-deficient mice developed exacerbated malaria with either P.
      yoelii or P. chabaudi, compared with that seen in heterozygote controls.
      Moreover, type-2 cytokine knockout mice showed a similar time course of infection
      with either parasite compared with that seen with their controls. We conclude
      that the mechanism of resolution of these well characterized malarial infections
      cannot be linked definitely to these T(H1)- and T(H2)-associated cytokines as
      predicted by the T(H1)/T(H2)-CMI/AMI hypothesis.

PMID- 9030671
TI  - Elevated free fatty acid concentrations in lipemic sera reduce protein binding of
      valproic acid significantly more than phenytoin.
AB  - Higher concentrations of free valproic acid and phenytoin have been reported in
      patients with uremia and liver disease. Free fatty acids also displace valproic
      acid and phenytoin. This is a study of the magnitude of displacement of valproic
      acid and phenytoin from protein binding by free fatty acid in lipemic sera.
      Higher concentrations of free fatty acids in lipemic sera affected protein
      binding of valproic acid significantly more than that of phenytoin. Supplementing
      normal sera with free fatty acids also increased the free concentrations of both
      valproic acid and phenytoin as expected, but the observed effect was several
      times higher in magnitude with valproic acid. There was an increased free
      fraction of valproic acid in patients who received valproic acid and had
      hypertriglyceridemia. In a patient with uremia, there was also a significant
      increase in free valproic acid concentration after routine hemodialysis caused by
      an increase in free fatty acid concentration secondary to hemodialysis. Increased
      protein binding of valproic acid in sera was observed after treatment with
      activated charcoal because charcoal can remove free fatty acid. Because higher
      free fatty acid concentration significantly affects protein binding of valproic
      acid, careful monitoring of free valproic acid in patients with lipid disorder
      may be beneficial.

PMID- 9030672
TI  - Thyroid function in children with different lipoprotein profiles: observations in
      a biracial (black/white) population--the Bogalusa Heart Study.
AB  - Abnormalities of thyroid function are associated with hyperlipidemia, a risk
      factor for coronary artery disease that starts in childhood. We investigated the
      age-, race-, and sex-related differences in thyroid function and its relation to
      serum lipoprotein levels in children (n = 363) aged 6 to 18 years from the
      biracial (black/white) community of Bogalusa, Louisiana, using an ultrasensitive
      thyroid-stimulating hormone (TSH) assay. Serum levels of lipoprotein cholesterol
      fractions, triglycerides, triiodothyronine (T3), thyroxine (T4), and the Tanner
      stage of sexual development were determined. Serum T3 (P < 0.0001), T4 (P <
      0.0001), and TSH (P < 0.0020) levels decreased significantly with Tanner stage.
      Serum T4 levels were significantly higher (P < 0.0001) in both black and white
      females than their male counterparts. An unexpected finding was a significantly
      increased mean serum TSH in whites (2.09 + 0.91; mean + standard error of mean)
      when compared to blacks (1.74 + 0.10; P = 0.0185). Overall, no significant
      correlation was noted between serum lipoprotein variables and TSH. However, those
      with the highest low-density lipoprotein to very low-density lipoprotein
      cholesterol fractions had a higher T4 and a T4/TSH ratio than those with the
      lowest low-density lipoprotein to very low-density lipoprotein cholesterol
      fractions. In summary, it is concluded that there is no simple relationship
      between lipoproteins and TSH or thyroid hormone levels in children.

PMID- 9030673
TI  - Is kidney length a good predictor of kidney volume?
AB  - Kidney length is commonly used to determine kidney size; however, its
      relationship to kidney volume is not well established. This study evaluated the
      association between kidney length and kidney volume. Eighteen healthy adults (9
      men and 9 women) consented to take part in this prospective study; all 18
      underwent spiral computerized tomography (CT) of the kidneys, 14 of 18 also
      underwent kidney ultrasound. Kidney volume was measured by totaling the areas of
      the CT scan cuts, and kidney length was measured both on the kidney ultrasound
      and on the CT scan. Each independent variable, CT length (CTL) and ultrasound
      length (USL), was regressed against the dependent variable, kidney volume. Kidney
      length explained only 10% of the variability of the volume, although length x
      width was a better predictor of kidney volume (r = 0.72, P < 0.001). It was
      concluded that kidney length does not reliably predict kidney volume and that
      other methods, both clinical and radiologic, should be considered when a more
      exact determination of renal volume is clinically relevant.

PMID- 9030674
TI  - Modulatory effect of esophageal intraluminal mechanical and chemical stressors on
      salivary prostaglandin E2 in humans.
AB  - As has been demonstrated, infusion of hydrochloric acid (HCl) and pepsin into the
      human esophageal lumen, which mimics the natural gastroesophageal reflux, results
      in a significant increase in salivary volume, salivary bicarbonate and epidermal
      growth factor. However, the impact of intraluminal acid/pepsin solution on
      salivary prostaglandin E2 (sPGE2), the major protective factor of the upper
      alimentary tract, has never been explored. Therefore, using the newly developed
      esophageal perfusion model, the impact of both mechanical and chemical stimuli of
      the esophagus on sPGE2 secretion in humans was studied. Salivary PGE2 was
      assessed in saliva collected during basal conditions, chewing of parafilm,
      placement of intraesophageal tubing, inflation of intraesophageal balloons, and
      perfusion with sodium chloride, HCl, or HCl/pepsin solutions. The concentration
      of sPGE2 was measured using the RIA kit from Amersham (Arlington Heights, IL)
      after the solid-phase extraction and derivatization. The concentration of sPGE2
      in the basal saliva was (mean +/- standard error of mean) 186 +/- 31 pg/mL and
      was similar during the chewing of parafilm (171 +/- 32 pg/mL). The placement of
      intraesophageal tubing, however, resulted in a significant decline of sPGE2
      concentration to the value of 91 +/- 22 pg/mL (P < 0.01). This decline was
      maintained when intraesophageal balloons, which compartmentalized a 7.5 cm
      perfused segment of the esophagus, were inflated (86 +/- 17 pg/mL; P < 0.01).
      This decline was potentiated further when subsequent perfusion with saline was
      implemented to reach the lowest value of 46 +/- 17 pg/mL (P < 0.001 versus basal
      and P < 0.05 versus tubing and balloon evoked values) at the end of the perfusing
      procedure. Esophageal perfusion with acid and acid/pepsin solution, however,
      partly restored the significant decline in sPGE2 concentration observed during
      prolonged perfusion with saline. The sPGE2 output during basal conditions was 89
      +/- 13 pg/min and increased dramatically during stimulation by placement of
      intraesophageal tubing (241 +/- 48 pg/min; P < 0.01) and inflation of
      intraesophageal balloons (244 +/- 48 pg/min; P < 0.01). Subsequent esophageal
      perfusion with saline resulted in a gradual decline of sPGE2 output evoked by
      mechanical stimuli that reached the final value of 178 +/- 39, which was not
      significantly different from that observed in the basal condition (P < 0.1 versus
      basal value). Introduction of HCl and pepsin into the perfusing solution
      significantly prevented the decline of sPGE2 output observed during perfusion
      with saline (252 +/- 36 pg/min; P < 0.01 versus basal). The modulatory impact of
      mechanical and chemical stimulation on sPGE2, demonstrated for the first time in
      humans, may suggest the potential contribution of salivary prostanoids to the
      maintenance of the integrity of the esophageal mucosa.

PMID- 9030675
TI  - Emergency room visits despite the availability of primary care: a study of high
      risk inner city infants.
AB  - Very low birth weight preterm infants randomized to receive comprehensive primary
      care in an ongoing clinical trial were prospectively evaluated to determine the
      cause of frequent emergency room use despite the availability of a primary
      healthcare provider and specific social services. Mothers were interviewed to
      assess knowledge of available resources, when to seek medical attention, and the
      perception of problems that limit access to health care. The healthcare provider
      was not called before 49% of the emergency room visits and mothers often did not
      recall what infant signs needed medical attention. Seventy-nine percent of
      emergency room visits were delayed more than 10 hours; and 15 of 62 (24%)
      emergency room visits resulted in admittance to the hospital. We conclude that in
      high-risk populations, the mere availability of primary care does not assure that
      it will be used. New strategies to help parents know when and how to use services
      are needed to increase the delivery of primary care.

PMID- 9030676
TI  - Insulin resistance: a common factor in the triad of dyslipidemia, hypertension,
      and coronary artery disease?
AB  - In addition to the goal of controlling elevated blood pressure in patients with
      hypertension improving Dyslipidemia associated with insulin resistance may be an
      important element in preventing coronary artery disease. Antihypertensive
      treatment may differ based on the pathophysiology present. It appears that the
      evidence that supports the development of lipid abnormalities in patients who
      have insulin resistance is growing. In such patients the morbidity and mortality
      associated with coronary artery disease may be significantly decreased by
      selecting agents with favourable metabolic consequences.

PMID- 9030677
TI  - Increased anion gap after liver transplantation.
AB  - Massive fibrinolysis after a liver transplant resulted in oliguric renal failure
      and necessitated the continuous infusion of large quantities of fresh frozen
      plasma. With the increase in plasma protein concentration, there was a
      simultaneous increase in the anion gap. These two parameters, the anion gap and
      total protein or albumin level in the blood, demonstrated a high degree of
      correlation. Weaker but significant correlations were found in a retrospective
      analysis of patients with a variety of renal diseases and a population of long
      term peritoneal but not hemodialysis patients. This entity of hyperproteinemic
      acidosis should be added to the list of high anion gap acidoses.

PMID- 9030678
TI  - Crohn's disease associated with pellagra and increased excretion of 5
      hydroxyindolacetic acid.
AB  - A 47-year-old woman with seronegative polyarthritis, diarrhea, and
      photosensitivity dermatitis was found to have Crohn's disease and pellagra. The
      presence of high values of 5-hydroxyindolacetic acid in the urine began the
      exhaustive investigations and finally enterotomy. No mass lesion was found.
      Argyrophilic cells were not increased in areas of inflamed intestinal mucosa or
      the normal mucosa. The disagreement between biochemical and histologic findings
      was attributed to sampling error. Antiinflammatory treatment for Crohn's disease
      was given and the gastrointestinal and articular symptoms improved, excretion of
      5-hydroxyindolacetic acid returned to normal and there was no relapse of
      pellagra. Pellagra as a complication of Crohn's disease has been described in 4
      cases; malnutrition and intestinal malabsorption were the proposed mechanisms for
      the niacin deficiency and pellagra of those patients. In the current case, the
      pathogenesis of pellagra may be accounted to wastage of tryptophan by an
      increased pool of intestinal argyrophilic cells, suggested by increased urinary
      excretion of 5-hydroxyindolacetic acid.

PMID- 9030679
TI  - Bartter's syndrome, supraventricular tachycardia, mitral valve prolapse, and
      asthma: a therapeutic challenge.
AB  - A 25-year-old man with acquired Bartter's syndrome, mitral valve prolapse, and
      supraventricular tachycardia secondary to a low atrial focus was diagnosed with
      asthma. The unique aspects of managing these coexisting diseases are evaluated.
      Calculation of free-water clearance in the diagnosis of Bartter's syndrome and
      the etiology and characteristics of the syndrome are discussed.

PMID- 9030680
TI  - Near-fatal but reversible acute renal failure after massive ibuprofen ingestion.
AB  - Adverse effects of nonsteroidal antiinflammatory drugs are frequently seen
      because of the extremely widespread use of these agents. Nephrotoxicity is
      relatively uncommon with the drug ibuprofen and, when present, is usually rapidly
      reversible. Fatal acute renal failure from ibuprofen has never been reported.
      This is the case of a patient with multiple medical problems who had near-fatal
      acute renal failure after the ingestion of 36 g ibuprofen, and who required
      dialysis for several months, at which point renal function improved. He did not
      admit to ibuprofen ingestion at the time of admission, and some of the clinical
      manifestations, including anion gap metabolic acidosis, respiratory alkalosis,
      and mental status abnormalities, could be accounted for by renal failure. Hence,
      this diagnosis was not considered during admission. However, the patient admitted
      to ibuprofen ingestion after his mental status improved with hemodialysis. A
      number of other variables were present that probably contributed to the
      development of acute renal failure, such as the presence of long-term renal
      insufficiency, hypotension, and possibly other drug ingestion. Acute renal
      failure with massive ibuprofen ingestion may be fatal or may show delayed
      reversibility even after necessitating dialysis for several months.

PMID- 9030681
TI  - Impact of dietary yogurt on immune function.
AB  - Studies of the effects of yogurt on immunity and atopic diseases have suggested
      improvements in cytokine (interleukin-2 and interferon-gamma) responses and
      clinical scores in patients with allergic rhinitis. This study compares
      prospectively immune parameters of participants who received 16 oz of yogurt
      versus 16 oz of milk/day in a randomized cross-over design. Yogurt that contained
      live, active Lactobacillus bulgaricus and Streptococcus thermophilus or 2% milk
      was consumed for one month each. Twenty otherwise healthy adults with atopic
      histories documented by skin testing were enrolled. Immune studies were performed
      at the beginning and end of the two 1-month study phases, separated by a 2-week
      washout period. These studies included measurements of cellular, humoral, and
      phagocytic function. No adverse events were noted in either group. No significant
      improvements in any immune parameter were noted. The consumption of yogurt that
      contained the live active bacteria L bulgaricus and S thermophilus does not
      appear to enhance immune function in atopic individuals at the dosage and
      duration used in this study.

PMID- 9030682
TI  - Unique requirements for retinoid-dependent transcriptional activation by the
      orphan receptor LXR.
AB  - LXR is an orphan nuclear receptor that confers retinoid responsiveness to the
      retinoid X receptor (RXR) by its interaction on a specific response element
      called an LXRE. To understand the mechanism of this response, three
      characteristics were identified that are crucial to activation of the RXR-LXR
      complex. First, the orientation of the RXR-LXR heterodimer on DNA indicates that
      as the ligand-binding partner, RXR occupies the 5' half-site of the response
      element. Next, the sequence specificity of the LXRE was determined in order to
      identify residues required for retinoid activation of the heterodimer.
      Remarkably, subtle changes in the nucleotide sequence of the LXRE half-sites that
      do not substantially alter DNA binding of the RXR-LXR heterodimer have a
      significant effect on the ability of the complex to be activated by ligand.
      Finally, we characterized the contributions of the activation domains of each
      receptor to the trans-activation potential of the RXR-LXR heterodimer.
      Surprisingly, our results show that only the activation domain of LXR is required
      for retinoid activation. Taken together, these results demonstrate the existence
      of a unique form of communication between heterodimer partners in which the
      activation potential of one receptor (LXR) is enabled by ligand binding to its
      partner (RXR). Furthermore, we conclude that RXR ligand activation potential is
      not dictated solely by its position on DNA, but is influenced by other factors
      such as the receptor partner and sequence of the response element.

PMID- 9030683
TI  - The phantom ligand effect: allosteric control of transcription by the retinoid X
      receptor.
AB  - Regulation of gene expression via allosteric control of transcription is one of
      the fundamental concepts of molecular biology. Studies in prokaryotes have
      illustrated that binding of small molecules or ligands to sequence-specific
      transcription factors can produce conformational changes at a distance from the
      binding site. These ligand-induced changes can dramatically alter the DNA binding
      and/or trans-activation abilities of the target transcription factors. In this
      work, analysis of trans-activation by members of the steroid and thyroid hormone
      receptor superfamily identifies a unique form of allosteric control, the phantom
      ligand effect. Binding of a novel ligand (LG100754) to one subunit (RXR) of a
      heterodimeric transcription factor results in a linked conformational change in
      the second noncovalently bound subunit of the heterodimer (RAR). This
      conformational change results in both the dissociation of corepressors and
      association of coactivators in a fashion mediated by the activation function of
      the non-liganded subunit. Without occupying the RAR hormone binding pocket,
      binding of LG100754 to RXR mimics exactly the effects observed when hormone is
      bound to RAR. Thus, LG100754 behaves as a phantom ligand.

PMID- 9030684
TI  - Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating a
      requirement for Sos1 in EGFR signaling and development.
AB  - We have investigated the role of the mammalian Son of sevenless 1 (Sos1) protein
      in growth factor signaling in vivo by generating mice and cell lines that lacked
      the Sos1 protein. Homozygous null embryos were smaller than normal, died mid
      gestation with cardiovascular and yolk sac defects, and their fibroblasts showed
      reduced mitogen-activated protein kinase activation in response to epidermal
      growth factor (EGF). An intercross of mice mutant for Sos1 and the EGF receptor
      (EGFR) demonstrated that a heterozygous mutation in Sos1 dominantly enhanced the
      phenotype of a weak allele of the EGFR allele (wa-2). These animals had
      distinctive eye defects that closely resembled those seen in mice that were null
      for the EGFR or its ligand, TGF alpha. Our findings provide the first
      demonstration of a functional requirement for Sos1 in growth factor signaling in
      vivo. They also show that the genetic test of enhancement of weak receptor allele
      by heterozygous mutation in one component represents a powerful tool for
      analyzing the ras pathway in mammals.

PMID- 9030685
TI  - A novel translational repressor mRNA is edited extensively in livers containing
      tumors caused by the transgene expression of the apoB mRNA-editing enzyme.
AB  - Transgene expression of the apolipoprotein B mRNA-editing enzyme (APOBEC-1)
      causes dysplasia and carcinoma in mouse and rabbit livers. Using a modified
      differential display technique, we identified a novel mRNA (NAT1 for novel APOBEC
      1 target no. 1) that is extensively edited at multiple sites in these livers. The
      aberrant editing alters encoded amino acids, creates stop codons, and results in
      markedly reduced levels of the NAT1 protein in transgenic mouse livers. NAT1 is
      expressed ubiquitously and is extraordinarily conserved among species. It has
      homology to the carboxy-terminal portion of the eukaryotic translation initiation
      factor (eIF) 4G that binds eIF4A and eIF4E to form eIF4F. NAT1 binds eIF4A but
      not eIF4E and inhibits both cap-dependent and cap-independent translation. NAT1
      is likely to be a fundamental translational repressor, and its aberrant editing
      could contribute to the potent oncogenesis induced by overexpression of APOBEC-1.

PMID- 9030686
TI  - Phosphorylation of the ASF/SF2 RS domain affects both protein-protein and protein
      RNA interactions and is necessary for splicing.
AB  - ASF/SF2 is a member of a conserved family of splicing factors known as SR
      proteins. These proteins, which are necessary for splicing in vitro, contain one
      or two amino-terminal RNP-type RNA-binding domains and an extensively
      phosphorylated carboxy-terminal region enriched in repeating Arg-Ser dipeptides
      (RS domains). Previous studies have suggested that RS domains participate in
      protein-protein interactions with other RS domain-containing proteins. Here we
      provide evidence that the RS domain of unphosphorylated recombinant ASF/SF2 is
      necessary, but not sufficient, for binding to the U1 snRNP-specific 70-kD protein
      (70K) in vitro. An apparent interaction of the isolated RS domain with 70K was
      observed if contaminating RNA was not removed, suggesting a nonspecific bridging
      between the basic RS domain, RNA, and 70K. In vitro phosphorylation of
      recombinant ASF/SF2 both significantly enhanced binding to 70K and also
      eliminated the RS domain-RNA interaction. Providing evidence that these
      interactions are relevant to splicing, ASF/SF2 can bind selectively to U1 snRNP
      in an RS domain-dependent, phosphorylation-enhanced manner. We also describe
      conditions that reveal for the first time a phosphorylation requirement for
      ASF/SF2 splicing activity in vitro.

PMID- 9030687
TI  - Ultraviolet radiation sensitivity and reduction of telomeric silencing in
      Saccharomyces cerevisiae cells lacking chromatin assembly factor-I.
AB  - In vivo, nucleosomes are formed rapidly on newly synthesized DNA after polymerase
      passage. Previously, a protein complex from human cells, termed chromatin
      assembly factor-I (CAF-I), was isolated that assembles nucleosomes preferentially
      onto SV40 DNA templates that undergo replication in vitro. Using a similar assay,
      we now report the purification of CAF-I from the budding yeast Saccharomyces
      cerevisiae. Amino acid sequence data from purified yeast CAF-I led to
      identification of the genes encoding each subunit in the yeast genome data base.
      The CAC1 and CAC2 (chromatin assembly complex) genes encode proteins similar to
      the p150 and p60 subunits of human CAF-I, respectively. The gene encoding the p50
      subunit of yeast CAF-I (CAC3) is similar to the human p48 CAF-I subunit and was
      identified previously as MSI1, a member of a highly conserved subfamily of WD
      repeat proteins implicated in histone function in several organisms. Thus, CAF-I
      has been conserved functionally and structurally from yeast to human cells. Genes
      encoding the CAF-I subunits (collectively referred to as CAC genes) are not
      essential for cell viability. However, deletion of any CAC gene causes an
      increase in sensitivity to ultraviolet radiation, without significantly
      increasing sensitivity to gamma rays. This is consistent with previous
      biochemical data demonstrating the ability of CAF-I to assemble nucleosomes on
      templates undergoing nucleotide excision repair. Deletion of CAC genes also
      strongly reduces silencing of genes adjacent to telomeric DNA; the CAC1 gene is
      identical to RLF2 (Rap1p localization factor-2), a gene required for the normal
      distribution of the telomere-binding Rap1p protein within the nucleus. Together,
      these data suggest that CAF-I plays a role in generating chromatin structures in
      vivo.

PMID- 9030688
TI  - RLF2, a subunit of yeast chromatin assembly factor-I, is required for telomeric
      chromatin function in vivo.
AB  - In the yeast Saccharomyces cerevisiae, telomere repeat DNA is assembled into a
      specialized heterochromatin-like complex that silences the transcription of
      adjacent genes. The general DNA-binding protein Rap1p binds telomere DNA repeats,
      contributes to telomere length control and to telomeric silencing, and is a major
      component of telomeric chromatin. We identified Rap1p localization factor 2
      (RLF2) in a screen for genes that alleviate antagonism between telomere and
      centromere sequences on plasmids. In rlf2 mutants, telomeric chromatin is
      perturbed: Telomeric silencing is reduced and Rap1p localization is altered. In
      wild-type cells, Rap1p and telomeres localize to bright perinuclear foci. In rlf2
      strains, the number of Rap1p foci is increased, Rap1p staining is more diffuse
      throughout the nucleus, Rap1p foci are distributed in a much broader perinuclear
      domain, and nuclear volume is 50% larger. Despite the altered distribution of
      Rap1p in rlf2 mutant cells, fluorescence in situ hybridization to subtelomeric
      repeats shows that the distribution of telomeric DNA is similar in wild-type and
      mutant cells. Thus in rlf2 mutant cells, the distribution of Rap1p does not
      reflect the distribution of telomeric DNA. RLF2 encodes a highly charged coiled
      coil protein that has significant similarity to the p150 subunit of human
      chromatin assembly factor-I(hCAF-I), a complex that is required for the DNA
      replication-dependent assembly of nucleosomes from newly synthesized histones in
      vitro. Furthermore, RLF2 is identical to CAC1, a subunit of yeast chromatin
      assembly factor-I (yCAF-I) which assembles nucleosomes in vitro. In wild-type
      cells, epitope-tagged Rlf2p expressed from the GAL10 promoter localizes to the
      nucleus with a pattern distinct from that of Rap1p, suggesting that Rlf2p is not
      a component of telomeric chromatin. This study provides evidence that yCAF-I is
      required for the function and organization of telomeric chromatin in vivo. We
      propose that Rlf2p facilitates the efficient and timely assembly of histones into
      telomeric chromatin.

PMID- 9030689
TI  - Disruption of the terminal base pairs of retroviral DNA during integration.
AB  - Integrase catalyzes two essential steps in the integration of the retroviral
      genome--end processing and strand transfer--both of which require the interaction
      of integrase with viral att sites located at the ends of viral genomic DNA. These
      two different polynucleotidyl transfer reactions are apparently carried out by a
      single active site. The end product of these reactions, the integrated provirus,
      does not undergo transposition and remains a stable part of the host cell genome.
      A central question in understanding the mechanism of integration is how a single
      active site accomplishes two distinct polynucleotidyl transfer reactions. We
      propose that integrase distorts DNA substrates to accommodate both reactions
      within the active site. Evidence is provided for disruption of base-pairing at
      the terminus of viral DNA during end processing. Furthermore, we show that this
      end fraying is a required step in end processing and that it appears to occur
      after initial binding of the viral DNA end. This requirement for base-pair
      disruption may account for the inability of integrase to use internal sites on
      DNA molecules as viral att sites. The specificity of integrase for DNA ends
      solves a problem posed by the long terminal repeat structure of the viral genome,
      and may help to prevent transposition of integrated proviruses.

PMID- 9030691
TI  - Topoisomerase I enhances TFIID-TFIIA complex assembly during activation of
      transcription.
AB  - The mechanism of coactivation by DNA topoisomerase I (topo I) was examined in a
      highly defined in vitro transcription system containing Pol II and purified
      factors. Both stimulation of the basal reaction and coactivation occurred
      dependent on TAF(II)s. Activation was first observed at the TFIID-TFIIA stage of
      initiation and maximal activation required the concomitant presence of TFIID,
      TFIIA, topo I, and activator. Electrophoretic mobility shift assay demonstrated a
      dramatic enhancement in the formation of the TFIID-TFIIA complex by topo I and
      activator, dependent on the TAF(II)s. DNase I footprinting confirmed this
      recruitment. A catalytically inactive topo I, which coactivated transcription,
      similarly stimulated the rapid formation of the TFIID-TFIIA complex in the
      presence of activator. A camptothecin-mediated DNA cleavage assay demonstrated
      the recruitment of topo I to the template by TFIID. Topo I likely functions
      during activation by enhancing the formation of an active TFIID-TFIIA complex on
      the promoter.

PMID- 9030690
TI  - HBP1: a HMG box transcriptional repressor that is targeted by the retinoblastoma
      family.
AB  - A prominent feature of cell differentiation is the initiation and maintenance of
      an irreversible cell cycle arrest with the complex involvement of the
      retinoblastoma (RB) family (RB, p130, p107). We have isolated the HBP1
      transcriptional repressor as a potential target of the RB family in
      differentiated cells. By homology, HBP1 is a sequence-specific HMG transcription
      factor, of which LEF-1 is the best-characterized family member. Several features
      of HBP1 suggest an intriguing role as a transcriptional and cell cycle regulator
      in differentiated cells. First, inspection of the HBP1 protein sequence revealed
      two consensus RB interaction motifs (LXCXE and IXCXE). Second, HBP1 interaction
      was selective for RB and p130, but not p107. HBP1, RB, and p130 levels are all up
      regulated with differentiation; in contrast, p107 levels decline. Third, HBP1 can
      function as a transcriptional repressor of the promoter for N-MYC, which is a
      critical cell cycle and developmental gene. Fourth, because the activation of the
      N-MYC promoter in cycling cells required the E2F transcription factor, we show
      that E2F-1 and HBP1 represent opposite transcriptional signals that can be
      integrated within the N-MYC promoter. Fifth, the expression of HBP1 lead to
      efficient cell cycle arrest. The arrest phenotype was manifested in the presence
      of optimal proliferation signals, suggesting that HBP1 exerted a dominant
      regulatory role. Taken together, the results suggest that HBP1 may represent a
      unique transcriptional repressor with a role in initiation and establishment of
      cell cycle arrest during differentiation.

PMID- 9030692
TI  - Inducible expression of N-methyl-D-aspartate (NMDA) receptor channels from cloned
      cDNAs in CHO cells.
AB  - To develop a drug screening system, we introduced expression vectors carrying the
      mouse N-methyl-D-aspartate (NMDA) receptor channel epsilon1 and zeta1 subunit
      cDNAs under the promoter of the Drosophila heat shock protein hsp70 into Chinese
      hamster ovary (CHO) cells. We selected clonal cell lines by means of RNA blot
      hybridization and fura-2 fluorometry. One of these cell lines, ZE1-1, optimally
      expressed the epsilon1 and zeta1 subunit mRNAs when induced by an incubation at
      43 degrees C for 2 h. Heated ZE1-1 cells exhibited the NMDA-induced intracellular
      Ca2+ elevation, whereas unheated they showed no such response. NMDA and L
      glutamate, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)
      and kainate, induced an increase in the intracellular Ca2+ concentration. The
      response to the agonists was marginal in the absence of glycine, and diminished
      by Mg2+ and NMDA receptor antagonists. Furthermore, exposure to agonists of ZE1-1
      cells expressing the epsilon1/zeta1 NMDA receptor channel resulted in the release
      of lactate dehydrogenase (LDH) activity in the culture medium indicating agonist
      induced cell death. NMDA receptor antagonists inhibited the LDH activity release.
      These results suggest that ZE1-1 cells will provide a useful screening system for
      novel drugs acting on the epsilon1/zeta1 NMDA receptor channel.

PMID- 9030693
TI  - The expression of mRNA for a kappa opioid receptor in the substantia nigra of
      Parkinson's disease brain.
AB  - We molecularly cloned the kappa opioid receptor from a human substantia nigra
      cDNA library. When expressed in HEK293 cells, the cloned receptor had similar
      pharmacological characteristics to the rat kappa opioid receptor. Northern blot
      analysis showed the presence of a single transcript of about 6 kb in size for
      mRNA prepared from the substantia nigra. Using in situ hybridization
      histochemistry, we studied the expression of this receptor in postmortem human
      brains from control and Parkinson's disease subjects. Kappa opioid receptor mRNA
      was present in melanized (possibly dopaminergic) neurons of the substantia nigra
      and the nucleus paranigralis. On the other hand, Parkinson's disease brains had
      markedly fewer melanized neurons, as expected, and correspondingly very low or
      background levels of mRNA for the kappa opioid receptor. However, in some cases,
      remaining melanized neurons still expressed the receptor mRNA. From these results
      we suggest that dopaminergic neurons in the human substantia nigra and the
      nucleus paranigralis synthesize kappa opioid receptors and express them in their
      perikarya and their terminal regions. The kappa opioid receptor expressed in the
      melanized neurons may play a role in the normal function of dopaminergic systems
      and possibly in the etiology of Parkinson's disease.

PMID- 9030694
TI  - Expression of the AMPA-selective receptor subunits in the vestibular nuclei of
      the chinchilla.
AB  - The distribution of the AMPA type glutamate receptor has been investigated
      throughout the central nervous system; however, no detailed description of its
      distribution is available in the vestibular nuclei. In the present study, in situ
      hybridization histochemistry and immunohistochemistry were used to localize the
      messenger RNAs and proteins of the AMPA-selective receptor subunits GluR1, GluR2,
      GluR3 and GluR4 in the vestibular nuclei of the chinchilla. Immunohistochemistry
      with subunits specific antisera showed differential distribution of the subunits
      in the vestibular nuclei. GluR2/3 antiserum labeled the most neurons, suggesting
      that many if not all vestibular neurons receive glutamatergic input. GluR1
      positive neurons were fewer than GluR2/3 immunoreactive neurons and GluR4
      immunoreactivity was found in the fewest number of neurons. GluR1 and GluR4
      immunoreactivity was also found in astrocyte-like structures. In situ
      hybridization with 35S-labeled complementary RNA probes confirmed the
      distribution of the AMPA receptor subunits obtained by immunohistochemistry.
      Quantitative analysis of the levels of hybridization showed a high degree of
      diversity in the levels of expression of the GluR2 subunit mRNA, with the highest
      levels of expression in the giant Deiter's cells of the lateral vestibular nuclei
      and the lowest levels in the small neurons throughout the vestibular nuclei. The
      subunit compositions of the AMPA receptors determine their physiological
      properties. Differential distribution and levels of expression of the receptor
      subunits in the vestibular nuclei may be related to the characteristics of
      information processing through the vestibular system.

PMID- 9030695
TI  - Stimulation of the A2A adenosine receptor increases expression of the tyrosine
      hydroxylase gene.
AB  - PC12 cells are known to express A2A adenosine receptors that are linked to
      adenylyl cyclase. We investigated the role played by A2A adenosine receptors in
      the expression of the rat tyrosine hydroxylase (TH) gene in PC12 cells. The A2A
      selective adenosine receptor agonist 2-(p-2-carboxyethyl)phenylethylamino)-5'-N
      ethylcarboxyamidoade nosine (CGS21680) caused TH mRNA levels to increase to more
      than twice the level of the untreated control. Transient transfection analysis
      demonstrated that the transcription of the TH gene was markedly enhanced upon
      treatment with CGS21680. The adenosine receptor-mediated TH gene expression was
      confirmed by the inhibitory effects that adenosine receptor antagonists had on
      the CGS21680 response. Mutational analysis of the 5' upstream region of the TH
      gene revealed that the cAMP response element (CRE) at -45 to -38 bp was
      responsible for the CGS21680 effect. Gel mobility shift assays revealed that six
      CRE-specific DNA-protein complexes were formed, and the amounts of three of them
      were significantly increased by treatment with CGS21680. Co-transfection with an
      expression vector containing protein kinase A (PKA) inhibitor markedly decreased
      the CGS21680 effect. The results suggest that stimulation of the A2A adenosine
      receptor leads to an elevated expression of the TH gene by changing the binding
      pattern of DNA binding proteins that interact with CRE through activation of
      protein kinase A.

PMID- 9030696
TI  - Regulation of cAMP response element binding protein (CREB) binding in the
      mammalian clock pacemaker by light but not a circadian clock.
AB  - Mammalian circadian rhythms are considered to be regulated by a clock pacemaker
      located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The molecular
      mechanism of entrainment and oscillation of circadian rhythm are not well
      understood but photic induction of immediate-early gene (IEG) expression in the
      SCN is thought to play a role. Here we show that under 12 h light:12 h dark (LD)
      condition, the cAMP response element binding protein (CREB) binding to cAMP
      responsive promoter element (CRE) of NMDAR1/zeta1 promoter region in the SCN is
      higher during the light than the dark by electro-mobility shift assay (EMSA).
      When animals are placed in constant dark, CREB DNA binding activity in the SCN is
      low and does not vary with circadian time when compared with cortex nuclear
      extract as a control. Most significantly, photic induction of CREB binding
      activity in the SCN occurs at all circadian times tested, indicating that CREB
      DNA binding in the SCN is not gated by the endogenous clock. These results
      implicate the role of CREB in photic neuronal signaling in the SCN and suggest
      that CREB DNA binding activities may not be regulated by a circadian clock.

PMID- 9030697
TI  - Effect of pentylenetetrazol on the expression of tyrosine hydroxylase mRNA and
      norepinephrine and dopamine transporter mRNA.
AB  - Seizure activity has been shown to have differential effects on the terminal
      content of the monoamines, norepinephrine (NE) and dopamine (DA). Induction of
      seizure activity reduces the terminal content of NE, while DA levels remain
      unchanged or slightly elevated. This study examined the effect of the
      chemoconvulsant pentylenetetrazol (PTZ) on the mRNA expression of regulatory
      proteins which maintain the terminal content of NE and DA (i.e., synthesis and re
      uptake). The areas examined were the noradrenergic neurons of the locus coeruleus
      (LC) and dopaminergic neurons of the substantia nigra pars compacta/ventral
      tegmentum area (SNpc/VTA) in the rat. In the LC, PTZ increased mRNA expression of
      the immediate early gene, c-fos, and mRNA expression of the synthesizing enzyme,
      tyrosine hydroxylase (TH), and the re-uptake protein, norepinephrine transporter
      (NET). This effect on TH and NET was observed only 1 day after the administration
      of PTZ. In contrast, PTZ did not alter the expression of c-fos mRNA in the
      SNpc/VTA, but reduced the expression of the dopamine transporter (DAT) mRNA. This
      effect was observed only 1 day after the administration of PTZ. TH mRNA
      expression in dopaminergic neurons was elevated initially in a manner similar to
      that observed in the LC. However, the effect of PTZ on TH mRNA expression in
      dopaminergic neurons was more prolonged (still elevated 3 days later). These
      results indicate that the chemoconvulsant PTZ has differential effects on the
      mRNA expression of regulatory systems (TH and neurotransporter proteins) in
      noradrenergic and dopaminergic neurons.

PMID- 9030698
TI  - mu-opioid receptor regulates CFTR coexpressed in Xenopus oocytes in a cAMP
      independent manner.
AB  - The objective of this study was to characterize the signaling mechanisms of the
      mu-opioid receptor in its coupling to the cystic fibrosis transmembrane
      conductance regulator (CFTR) when coexpressed in Xenopus oocytes. Because oocytes
      do not contain endogenous cAMP-regulated ion channels, the cAMP-modulated CFTR
      was coexpressed with receptors as a 'reporter' channel. Agonist treatment of
      oocytes coexpressing mu-opioid receptors, beta2-adrenergic receptors and CFTR
      produced Cl- currents in a dose-related manner and immunocytochemical analysis
      confirmed receptor expression. These data suggest that opioid agonists could
      activate adenylyl cyclase in this system to elevate cAMP levels. Heterotrimeric G
      protein betagamma-subunits acting on adenylyl cyclase type II would increase cAMP
      levels. The probable presence of adenylyl cyclase type II and other components of
      opioid signal transduction such as G(i alpha2), were demonstrated by RT-PCR.
      However, measurement of cAMP levels in individual oocytes by radioimmunoassay
      showed that opioid agonist application to oocytes expressing mu-opioid receptors,
      beta2-adrenergic receptors and CFTR did not increase cAMP levels, whereas
      application of the beta2-adrenergic agonist, isoproterenol, or IBMX alone did
      increase cAMP levels. Opioid-induced CFTR activation was not affected by either
      application of the broad spectrum kinase inhibitor, H7, nor by application of the
      specific PKA inhibitor, KT5720. Injection of free betagamma-subunits, which could
      activate the endogenous type II cyclase, was unable to produce measurable
      currents in oocytes expressing the CFTR. These studies indicate that opioid
      activation of the CFTR is not mediated through a cAMP/PKA pathway, by either
      betagamma-subunit activation of an adenylyl cyclase type II or promiscuous
      coupling to G(s alpha).

PMID- 9030699
TI  - Expression of the orphan receptor steroidogenic factor-1 mRNA in the rat medial
      basal hypothalamus.
AB  - Steroidogenic factor-1 (SF-1), an orphan receptor of the nuclear hormone receptor
      family, binds to the AAGGTCA motif in the promoter elements of several diverse
      target genes, including some that mediate steroidogenesis and sexual
      differentiation. In addition, SF-1 is expressed in embryonic forebrain,
      suggesting that it plays a role in neural development. This study was undertaken
      to study the distribution and regulation of SF-1 mRNA expression in the rat
      brain. SF-1 mRNA levels were measured in tissue dissections by ribonuclease
      protection assay. A 452 nt 32P-labeled cRNA probe, complementary to the putative
      ligand-binding domain of the rat SF-1 mRNA, was synthesized from the rat SF-1
      cDNA inserted into pBluescript II KS, using a Sty 1 fragment and T3 polymerase.
      The probe protected a single 390 nt transcript in the medial basal hypothalamus
      (MBH) and peripheral steroidogenic tissues of the male rat. The size of this
      protected band corresponded to that of the protected sense RNA standard (HindIII
      fragment of the SF-1 cDNA transcribed with T7 polymerase). No SF-1 mRNA was
      detected in the preoptic area, amygdala or cingulate cortex. The levels of SF-1
      mRNA in MBH were not affected by gonadectomy or androgen treatment, nor was there
      a sex difference in its expression in adults. In situ hybridization
      histochemistry revealed that SF-1 was localized to the ventromedial nucleus of
      the adult hypothalamus. The levels of SF-1 mRNA were high on gestational day 18
      after which they fell by approximately 30% and remained constant throughout
      gestation, the first week of neonatal life, and into adulthood. These results
      demonstrate that the gene encoding SF-1 is expressed in a discrete region of the
      rat hypothalamus and appears to be developmentally regulated, but not affected by
      gonadal hormones in adults.

PMID- 9030700
TI  - The Ca2+ binding protein, frequenin is a nervous system-specific protein in mouse
      preferentially localized in neurites.
AB  - Frequenin is a Ca2+-binding protein that has been implicated in the regulation of
      neurotransmitter release at the neuromuscular junction [15,16]. However, its
      cellular and subcellular localization in brain have not been determined.
      Therefore, we cloned mouse frequenin (Mfreq) and investigated its expression both
      in vivo and in vitro. The amino acid sequence of Mfreq is homologous to that of
      frequenins from other species. Northern and Western blot analyses indicated that
      the Mfreq mRNA is a single species of 4.2 kb, and that the protein has a mass of
      24 kDa protein on SDS gel, respectively. Expression of Mfreq is nervous system
      specific. However, Mfreq mRNA and protein are widely distributed in the brain,
      spinal cord, and dorsal root ganglia. Mfreq is expressed in early embryonic brain
      and the levels of Mfreq remain high throughout development. In situ hybridization
      and immunocytochemistry demonstrated that Mfreq is expressed primarily in neurons
      and presumptive astrocytes. The Mfreq protein was preferentially localized in
      neurites (dendrites and axons). Double immunofluorescence microscopy established
      that Mfreq was co-localized with the dendritic marker, MAP-2 and the synapse
      marker, SV2 in cultured hippocampal neurons. The distribution and subcellular
      localization of Mfreq may help understand its cellular function.

PMID- 9030701
TI  - Development of proenkephalin gene expression in rat neocortex: a non-radioactive
      in situ hybridization study.
AB  - Products of the proenkephalin gene are not only neurotransmitters but may also
      influence brain development. The ontogeny of the expression of the proenkephalin
      gene in neocortex was studied in embryonic and postnatal rats with in situ
      hybridization. At embryonic day 14, the proliferating cells in the ventricular
      zone strongly expressed the gene. Thereafter, the expression decreased and was
      hardly detectable up to embryonic day 21. At the day of birth and during the
      subsequent week, proliferating cells in the subventricular zone were labelled.
      The expression of the proenkephalin gene in proliferating neuronal and glial
      progenitors indicates that gene products may affect proliferation and/or
      commitment. In the neocortex, cells which strongly expressed the gene were first
      seen at postnatal day 7 in the outer part of the neocortex. Seven days later, a
      second band of positive cells had appeared in the inner part of the cortex, i.e.
      the adult pattern of distribution had been established. Thus, in rat neocortex
      the expression of the proenkephalin gene developed in an outside-first, inside
      last mode.

PMID- 9030703
TI  - Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative
      phosphorylation in association neocortex in Alzheimer disease.
AB  - We recently reported 50% decreases in mRNA levels of mitochondrial DNA (mtDNA)
      encoded cytochrome oxidase (COX) subunits I and III in Alzheimer disease (AD)
      brains. The decreases were observed in an association neocortical region
      (midtemporal cortex) affected in AD, but not in the primary motor cortex
      unaffected in AD. To investigate whether the decreases are specific to mtDNA
      encoded mRNA, we extended this analysis to nuclear DNA (nDNA)-encoded subunits of
      mitochondrial enzymes of oxidative phosphorylation (OXPHOS). Brains from five AD
      patients showed 50-60% decreases in mRNA levels of nDNA-encoded subunit IV of COX
      and the beta-subunit of the F0F1-ATP synthase in midtemporal cortex compared with
      mRNA levels from midtemporal cortex of control brains. In contrast, these mRNAs
      were not reduced in primary motor cortices of the AD brains. The amount of nDNA
      encoded beta-actin mRNA and the amount of 28S rRNA were not altered in either
      region of the AD brain. The results suggest that coordinated decreases in
      expression of mitochondrial and nuclear genes occur in association cortex of AD
      brains and are a consequence of reduced neuronal activity and downregulation of
      OXPHOS machinery.

PMID- 9030702
TI  - GluR2 glutamate receptor subunit flip and flop isoforms are decreased in the
      hippocampal formation in schizophrenia: a reverse transcriptase-polymerase chain
      reaction (RT-PCR) study.
AB  - GluR2 is the key subunit of heteromeric AMPA-preferring glutamate receptors.
      GluR2 mRNA has been shown by in situ hybridization histochemistry to be decreased
      in the hippocampal formation in schizophrenics. Here, a quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) method was used to investigate
      GluR2 expression further and to examine the relative abundance of its
      alternatively spliced mRNA isoforms ('flip' and 'flop') in 11 schizophrenics and
      11 matched controls. Compared to the controls, schizophrenics showed reduced
      expression of both isoforms relative to cyclophilin mRNA, but a greater loss of
      the flop isoform led to a higher flip:flop ratio. These differences were observed
      having controlled for the confounding effects of brain pH and age upon the mRNAs.
      We also found that the abundance of GluR2 mRNA correlates with that of the
      encoded subunit. This study has confirmed that, in schizophrenia, hippocampal
      GluR2 mRNA is reduced, and indicates that GluR2 subunits are composed of a higher
      proportion of the flip variant. These data extend the evidence for glutamatergic
      dysfunction in the disease. They suggest that signal transduction through
      hippocampal AMPA receptors is impaired in schizophrenia both by an overall loss
      of GluR2 expression, and by the change in flip:flop ratio which is predicted to
      alter the desensitization kinetics of the remaining GluR2 subunits.

PMID- 9030704
TI  - Isoform-specific binding of human apolipoprotein E to the non-amyloid beta
      component of Alzheimer's disease amyloid.
AB  - The non-A beta component (NAC) of Alzheimer's disease amyloid is a newly
      discovered 35 amino acid peptide found to be closely linked to the beta-amyloid
      fibrils in senile plaques. Apolipoprotein E (apoE) is another prominent
      constituent of senile plaques. In vitro studies have shown that apoE binds beta
      amyloid (A beta) with high avidity, but it is unknown to what extent apoE
      interacts with NAC. We examined the interactions between apoE and NAC and found
      that apoE bound synthetic NAC, forming a complex that resisted reducing agents
      and separation on SDS-PAGE. The complex could be formed using apoE from either
      purified human very low density lipoprotein (VLDL) particles, unfractionated
      human cerebrospinal fluid (CSF), or recombinant protein. The binding was
      established within 15 min upon mixing, and the interaction between NAC and apoE
      was dose-dependent and specific as revealed by competition experiments. The NAC
      apoE complex was affected by non-physiological pH, but not by reducing agents
      such as DTT or beta-mercaptoethanol. ApoE exists in different isoforms of which
      the apoE3 genotype is the most frequent. Notably, the apoE4 genotype has been
      linked to late-onset Alzheimer's disease. This study presents evidence that apoE3
      as well as apoE4 bind NAC, but the binding to apoE4 is about twice as strong as
      to apoE3. The isoform-specific binding of NAC to apoE may thus play an important
      role in amyloidogenesis and in the sequestering of apoE in senile plaques during
      the progress of Alzheimer's disease.

PMID- 9030705
TI  - Interaction of nuclear factors from young and old rat brain regions with
      regulatory sequences of the D2 dopamine receptor gene promoter.
AB  - Alterations in the number or functional state of D2 dopamine receptors have been
      implicated in the decreased motor abilities associated with normal aging,
      Parkinson's disease and other neurodegenerative diseases. Previous work has
      demonstrated a substantial decrease in D2 receptor-containing neurons, receptor
      proteins, steady-state mRNA levels, and the rate of mRNA synthesis with age in
      the rat striatum in particular and in mammalian brains in general. These
      observations suggest that one key area of regulatory control is at the level of
      transcriptional initiation and/or elongation. In the present study gel mobility
      shift experiments were used to assess the interaction of nuclear proteins from
      different rat brain regions with DNA containing putative DNA regulatory sites of
      the transcriptionally active rat D2 receptor gene promoter. Oligonucleotides
      containing either of the two SP1 binding sites immediately upstream of the
      primary transcriptional start site were bound by proteins found in nuclear
      extracts obtained from rat striatum, hippocampus, cortex, and cerebellum.
      Extracts from striatum and hippocampus formed predominantly low molecular weight
      complexes which do not contain SP1, as well as a small amount of high molecular
      weight complexes which may contain SP1 or an SP1-related protein. Cerebellar
      extracts formed two similar sets of complexes, but they were formed in roughly
      equal amounts. Extracts from cortex produced a more involved pattern of
      complexes, but still formed both high molecular weight complexes which contain
      SP1 and low molecular weight complexes which do not contain SP1. There were
      differences in the gel mobility as well as the relative amounts of complexes
      formed with the two SP1-specific oligonucleotides among different brain regions.
      With respect to possible age-related changes in transcription of the D2 dopamine
      receptor gene, there appeared to be no statistically significant difference in
      the DNA-protein complexes formed with striatal nuclear proteins from a population
      of young rats versus a population of old rats.

PMID- 9030706
TI  - Long-term histological follow-up of genetically modified myoblasts grafted into
      the brain.
AB  - Although primary muscle cells have been used as intracerebral vehicles for
      transgene expression in the past, data concerning their long-term survival after
      grafting into the brain, and the reaction of the host tissue to their
      implantation are lacking. In order to study these aspects, we have implanted,
      into the brain, primary muscle cells infected ex vivo with recombinant
      retroviruses carrying the E. coli LacZ gene. The muscle cells were delivered
      stereotaxically into different areas of the brain of adult rats and the grafts
      were analyzed up to 105 days after implantation. Intraventricular implantations
      did not lead to surviving grafts. In contrast, myoblasts developed when they were
      grafted into gray or white matter regions. They appeared numerous during the
      first weeks, but decreased dramatically in number over time. Over months, the
      grafts appeared to fill up with collagen. Astrocytes elaborated a continuous glia
      limitans surrounding the implant. Blood vessels coming from the host tissue were
      found within the grafts. The blood-brain barrier was permanently disrupted within
      the transplants. beta-Galactosidase activity was abundant during the first weeks,
      but decreased to a very low level subsequently. This decrease paralleled that of
      the number of muscle cells. In conclusion, myoblasts transplanted into the adult
      brain survived only temporarily, which implies a transient transgene expression.
      In addition, before being eliminated, muscle cells were surrounded by a glia
      limitans, which may limit exchanges with the host tissue. Altogether, these
      results suggest that intracerebral transplantation of myoblasts may possibly
      provide a relevant vehicle only for short-term delivery of a gene product.

PMID- 9030707
TI  - Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown
      and neuronal survival after transient cerebral ischemia in gerbils.
AB  - We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate
      on blood-brain barrier (BBB) breakdown and neuronal survival after transient
      cerebral ischemia in gerbils. BBB breakdown experiments were performed in
      pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid
      artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120
      mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter
      every hour up to 5 h. Fluorometric measurements quantified the blood-brain
      permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB
      breakdown as indicated by reduced levels of EB fluorescence. Neuronal count
      experiments were conducted in gerbils subjected to transient ischemia and 7 days
      of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was
      administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7
      days. SAM dose dependently protected the hippocampal CA1 neurons assessed by
      histopathological methods. SAM has a beneficial effect on the outcome of ischemic
      injury by reducing the BBB breakdown and neuronal death.

PMID- 9030708
TI  - Prodynorphin, proenkephalin and kappa opioid receptor mRNA responses to acute
      "binge" cocaine.
AB  - Previous studies showed that preprodynorphin (ppDyn) mRNA increases in caudate
      putamen while kappa opioid receptor (KOR) mRNA decreases in substantia nigra
      after 3 and 14 days "binge" cocaine. To further characterize opioid mRNA
      responses, rats were administered: saline; 1 day cocaine followed by 1 day
      saline; 1 day cocaine; or 2 days cocaine. ppDyn mRNA in caudate-putamen increased
      in both groups receiving cocaine on the final day compared to groups receiving
      saline. Preproenkephalin (ppEnk) mRNA in caudate-putamen increased, and KOR mRNA
      in substantia nigra decreased, after 2 days of cocaine. Thus ppDyn mRNA is
      elevated acutely by cocaine, while ppEnk and KOR mRNAs show a significant
      response only on the second day of "binge" cocaine.

PMID- 9030709
TI  - A recombinant adenovirus that directs secretion of biologically active kappa
      bungarotoxin from mammalian cells.
AB  - A novel Cre-lox system was used to construct an adenovirus encoding kappa
      bungarotoxin (kappa-Bgt), modified to be secreted by attachment of a bovine
      prolactin signal sequence at the N-terminus of the toxin. Western blot of medium
      from HEK-293 cells infected with the virus demonstrated that recombinant kappa
      Bgt (R-kappa-Bgt) was secreted. The biological activity of the secreted R-kappa
      Bgt was investigated in Xenopus oocytes that expressed neuronal nicotinic
      acetylcholine receptor (nAChR) subtypes alpha3beta2 and alpha2beta2. The
      recombinant toxin inhibited the response of alpha3beta2 type AChRs to ACh, but
      did not inhibit the response of alpha2beta2 type AChRs. These data demonstrated
      that the recombinant adenovirus directs the secretion of biologically active
      kappa-Bgt from a mammalian cell line. Because adenovirus can be used to infect
      post-mitotic cells, recombinant adenoviruses encoding biologically active
      peptides may be of use as delivery vehicles for in vivo experiments where
      repeated application of the purified peptide is unfeasible.

PMID- 9030710
TI  - Gerstmann-Straussler-Scheinker disease with the PRNP P102L mutation and valine at
      codon 129.
AB  - The most common mutation causing Gerstmann-Straussler-Scheinker (GSS) disease is
      P102L in the prion protein. Previously, this mutation has only been found in
      coupling with methionine at residue 129. We describe a patient with GSS disease
      in whom the P102L mutation is in coupling with valine at residue 129. The
      clinical presentation in P102L-V129 differs greatly from that seen in P102-M129
      patients.

PMID- 9030711
TI  - Quantitative analysis of dopamine receptor messages in the mouse cochlea.
AB  - Dopamine receptor isoforms were examined in the cochlea of the CBA(J) mouse by RT
      PCR analysis and nucleotide sequencing, utilizing primers specific for known
      dopamine receptor isoforms. Cochlear cDNA sequences corresponding to dopamine
      D2(long) and D3 receptors were amplified, whereas those representing D1A, D1B,
      D2(short), and D4 were not detected. Utilizing quantitative competitive PCR
      analysis, relative levels of dopamine receptor transcripts were found to be
      0.002, 0.014, 0.016, and 1.000 for D2(long) cochlea, D3 cochlea, D3 brain, and
      D2(long) brain, respectively. In the context of previously published findings,
      the current work provides key quantitative evidence necessary to establish that
      dopamine is a neurotransmitter in the auditory inner ear.

PMID- 9030712
TI  - Cortical NMDAR-1 gene expression is rapidly upregulated after seizure.
AB  - The promoter region of the NMDAR-1 receptor has a cis-regulatory element that is
      capable of binding to the NGFI-A family of transcription factors. Based on this
      observation, we hypothesized that situations that cause a change in NGFI-A levels
      would result in a change in NMDAR-1 expression. In these studies, we have
      demonstrated that a seizure results in a rapid significant increase in NMDAR-1
      mRNA and protein expression, at a time when NGFI-A protein levels are expected to
      be elevated. Our results indicate that control of NMDAR-1 expression is stimulus,
      time and tissue dependent.

PMID- 9030713
TI  - Localization of molecules involved in cytokine receptor signaling in the rat
      trigeminal ganglion.
AB  - The localization of some cytokine receptors and their downstream intracellular
      signaling molecules was examined in the trigeminal ganglia of rats. Among
      cytokine receptor components, we examined signal transduction subchain, gp130, IL
      2Rgamma and IL-5Rbeta, which are common to respective groups of cytokine
      receptors. Most of the sensory ganglion neurons expressed gp130, but not IL
      2Rgamma nor IL-5Rbeta. We further examined the localization of Janus kinase (JAK)
      family members which were reported to be associated with various kind of cytokine
      receptors and are thought to be implicated in major cytokine receptor-signaling
      pathways [6,9,11,13]. While JAK1 and Tyk2 were expressed in all the type of
      neurons, JAK2 was predominantly expressed in the small neurons. In addition, JAK3
      immunoreactivity was only found in satellite cells. The present results indicate
      that most of neurons express gp130, and that the localization of JAK family
      members differs with the cell type. This also suggests that the cytokine receptor
      signaling pathway may be different in neuronal and glial cells.

PMID- 9030714
TI  - Loss of Ref-1 protein expression precedes DNA fragmentation in apoptotic neurons.
AB  - Ref-1 is a bifunctional protein that has been implicated in the transcriptional
      regulation of AP-1 elements and in DNA repair. To investigate whether Ref-1 is
      involved in programmed cell death its expression was measured in the 21-day-old
      rat brain at various time-points following a moderate unilateral hypoxic-ischemic
      (HI) insult. The CA1 pyramidal cells, which are selectively vulnerable to HI
      injury, showed a significant decrease in Ref-1 immunoreactivity 48 h-7 days post
      insult. This loss of Ref-1 immunoreactivity may contribute to a decrease in
      endogenous repair activity and the development of apoptosis in the CA1 pyramidal
      cells.

PMID- 9030715
TI  - Rapid gene transfer into cultured hippocampal neurons and acute hippocampal
      slices using adenoviral vectors.
AB  - Primary cultures of hippocampal neurons were infected with an adenovirus coding
      for beta-galactosidase. Expression could be detected as early as 4 h after
      infection and steadily increased to high levels at 24 h without evidence for a
      functional impairment of the infected neurons. Similarly, adenovirus-mediated
      gene transfer into acute hippocampal slices was detectable 4 h after infection
      and could be localized to discrete areas of the CA1 region by microinjection of
      the virus stock solution. Infected slices were still suitable for
      electrophysiological experiments.

PMID- 9030716
TI  - Cell signalling through guanine-nucleotide-binding regulatory proteins (G
      proteins) and phospholipases.
AB  - Phospholipases are important enzymes in cell signal transduction since they
      hydrolyze membrane phospholipids to generate signalling molecules. Heterotrimeric
      guanine-nucleotide-binding regulatory proteins (G proteins) play a major role in
      their regulation by a variety of agonists that activate receptors with seven
      membrane-spanning domains. Phospholipases of the C type, which hydrolyze inositol
      phospholipids to yield inositol trisphosphate and diacylglycerol, are regulated
      by the alpha and betagamma subunits of certain heterotrimeric G proteins as well
      as by receptor-associated and non-receptor-associated tyrosine kinases.
      Phospholipases of the D type, which hydrolyze phosphatidylcholine to phosphatidic
      acid, are regulated by members of the ADP-ribosylation factor and Rho subfamilies
      of small G proteins, and by protein kinase C and other factors. This review
      presents recent information concerning the molecular details of G protein
      regulation of these phospholipases.

PMID- 9030717
TI  - Cell-surface acceleration of urokinase-catalyzed receptor cleavage.
AB  - The urokinase-type plasminogen activator (uPA) binds to a specific cell-surface
      receptor, uPAR. On several cell types uPAR is present both in the full-length
      form and a cleaved form, uPAR(2+3), which is devoid of binding activity. The
      formation of uPAR(2+3) on cultured U937 cells is either directly or indirectly
      mediated by uPA itself. In a soluble system, uPA can cleave purified uPAR, but
      the low efficiency of this reaction has raised doubts as to whether uPA is
      directly responsible for uPAR cleavage on the cells. We now report that uPA
      catalyzed cleavage of uPAR on the cell surface is strongly favored relative to
      the reaction in solution. The time course of uPA-catalyzed cleavage of cell-bound
      uPAR was studied using U937 cells stimulated with phorbol 12-myristate 13
      acetate. Only 30 min was required for 10 nM uPA to cleave 50% of the cell-bound
      uPAR. This uPA-catalyzed cleavage reaction was inhibited by a prior incubation of
      the cells with uPA inactivated by diisopropyl fluorophosphate, demonstrating a
      requirement for specific receptor binding of the active uPA to obtain the high
      efficiency cleavage of cell-bound uPAR. Furthermore, amino-terminal sequence
      analysis revealed that uPAR(2+3), purified from U937 cell lysates, had the same
      amino termini as uPAR(2+3), generated by uPA in a purified system. In both cases
      cleavage had occurred at two positions in the hinge region connecting domain 1
      and 2, between Arg83-Ala84 and Arg89-Ser90, respectively. The uPA-catalyzed
      cleavage of uPAR is a new negative-feedback regulation mechanism for cell-surface
      plasminogen activation. We propose that this mechanism plays a physiological role
      at specific sites with high local concentrations of uPA, thus adding another step
      to the complex regulation of this cascade reaction.

PMID- 9030718
TI  - Identification of POU-class homeobox genes in a freshwater sponge and the
      specific expression of these genes during differentiation.
AB  - We reported previously the identification of three homeobox-containing genes,
      prox1, prox2 and prox3, in sponges [Seimiya, M., Ishiguro, H., Miura.,K.,
      Watanabe, Y. & Kurosawa, Y. (1994) Eur. J. Biochem. 221, 219-225]. The
      transcripts of prox1 and prox2 were identified in cells at all stages of
      differentiation. In the present study, we have identified two POU-class homeobox
      genes, designated spou-1 and spou-2, in a freshwater sponge (Ephydatia
      fluviatilis). These genes each encode a POU-specific domain and a POU-type
      homeodomain. The amino acid sequences of the POU-specific domain and the POU-type
      homeodomain encoded by the spou-1 gene were 76% and 67% similar to those of the
      human Pit-1 gene, respectively. The amino acid sequence of the POU-specific
      domain encoded by the spou-2 gene was also most similar to that encoded by the
      human Pit-1 gene among all the POU-class homeobox genes that have been sequenced
      to date. In contrast to the results for prox1 and prox2, transcripts of the spou
      1 and spou-2 genes were identified in cells only at specific stages during the
      differentiation of the sponge.

PMID- 9030719
TI  - Molecular cloning and characterization of the chromosomal gene for human
      lactoperoxidase.
AB  - Lactoperoxidase (LPO) is an oxidoreductase secreted into milk, and plays an
      important role in protecting the lactating mammary gland and the intestinal tract
      of the newborn infants against pathogenic microorganisms. In this study, the
      human LPO chromosomal gene was molecularly cloned, and its gene organization was
      determined. The human LPO gene was found to be arranged with the myeloperoxidase
      (MPO) gene in a tail-to-tail manner. Similar to the human MPO and eosinophil
      peroxidase (EPO) genes, the human LPO gene is split by 11 introns and spans 28
      kb. Unlike most introns in mammalian gene, the 5' splice donor sequence of intron
      11 starts with GC instead of GT. When the minigene comprised of exon 11, intron
      11 and exon 12 of the human LPO gene was introduced into COS cells, the correct
      splicing of the intron was found, suggesting the intron 11 of the human LPO gene
      is functional. The coding sequence of human LPO consists of 2136 bp, and codes
      for a protein of 712 amino acids. The amino acid sequence of human LPO has 51%
      similarity with those of both human MPO and EPO, suggesting that these peroxidase
      genes have evolved from a common ancestral gene. On the other hand, the
      nucleotide sequences of the 5' promoter regions of these peroxidase genes exhibit
      no similarity among them, which agrees with their tissue-specific expression.

PMID- 9030720
TI  - Modified helix-loop-helix motifs of calmodulin--The influence of the exchange of
      helical regions on calcium-binding affinity.
AB  - The four calcium-binding sites, called the helix-loop-helix, or the EF-hand
      motifs, of calmodulin differ in their ion-binding affinities; this has been
      thought to arise due to the variations in the sequences of the loop regions where
      the ion binds. We focus attention here on the role of the flanking helical
      regions on the calcium-binding affinities. Peptides were synthesized in a manner
      that simulates the E and F helical flanks of site 4 (the strongest calcium
      binding site of the calmodulin) to sandwich the loop sequences of sites 1, 2, 3
      and 4 so as to produce peptides named 414, 424, 434 and 444, as well as using the
      helical flanks of site 1 (the weakest site) to produce peptides 111, 121, 131 and
      141. Calcium binding was monitored using the calcium-mimic dye Stains-all
      (4,4,4',5'-dibenzo-3,3'-diethyl-9-methyl-thiacarbocyanine bromide). Binding
      abilities were seen to increase several-fold when the E and F helices of site 1
      were replaced by those of site 4 (i.e., 111-414). In contrast, the intensity of
      circular dichroism induced in the absorption bands of the bound achiral dye
      decreased significantly when the helical flanks of site 4 were replaced with
      those of site 1 (i.e., 444-141). The helical flanks of site 4 impart greater
      binding ability to a given loop region, while the helical flanks of site 1 tend
      to weaken it.

PMID- 9030721
TI  - Regulatory mechanisms involved in activator-protein-1 (AP-1)-mediated activation
      of glutathione-S-transferase gene expression by chemical agents.
AB  - Induction of murine glutathione-S-transferase (GST) Ya gene expression by a
      variety of chemical agents is mediated by a regulatory element, EpRE, composed of
      an Ets and two adjacent activator protein-1 (AP-1)-like sites and activated by
      the Fos/Jun heterodimeric complex (AP-1). The mechanism of this induction was
      examined in the present study. We find that the regulation of EpRE-mediated GST
      Ya gene expression by 3-methylcholanthrene, tert-butylhydroquinone and beta
      naphthoflavone is associated with an induction of AP-1 DNA-binding activity and
      that the AP-1 complex induced in hepatoma cells by these chemicals contains
      members of the Fos and Jun protein families. We show that tert-butylhydroquinone
      induces c-fos gene expression and indicate the formation of a transcriptionally
      active AP-1 complex that contains Fos/Jun heterodimer. In F9 cells, which are
      considered to lack AP-1 complex, a careful examination reveals that tert
      butylhydroquinone induces a low level of an AP-1-related activity responsible for
      the enhanced expression of EpRE as well as of AP-1 reporter constructs. We find
      that protein phosphorylations mediate the activation of the GST Ya gene by
      chemical agents since okadaic acid, an inhibitor of protein phosphatases, can
      mimic this activation while protein kinase inhibitors abolish it. Evidence is
      presented that 3-methylcholanthrene, tert-butylhydroquinone and beta
      naphthoflavone use a signal transduction pathway to Fos/Jun-dependent GST Ya gene
      expression via Ras and protein-tyrosine kinase activity. Furthermore, we find
      that activation by phorbol 12-myristate 13-acetate, which uses both protein
      kinase C and protein-tyrosine kinase activities, may share a common pathway with
      these chemicals downstream of Ras.

PMID- 9030722
TI  - Characterization of the correlation between ATP-dependent aminophospholipid
      translocation and Mg2+-ATPase activity in red blood cell membranes.
AB  - Pseudosubstrates and inhibitors of ATPases were studied with respect to their
      capability to modulate the kinetic behavior of Mg2+-ATPase and aminophospholipid
      translocation in red blood cell ghosts. ATP was substituted by the
      pseudosubstrates of P-type ATPases acetyl phosphate and p-nitrophenyl phosphate.
      With both pseudosubstrates, aminophospholipid translocation from the outer to the
      inner leaflets of resealed erythrocyte ghosts could be observed, although with a
      significantly decreased velocity compared to that in presence of ATP, both with
      respect to phosphate hydrolysis and translocation. Similarly, the apparent
      affinities for the pseudosubstrates were much lower than for ATP. Among the
      inhibitors studied, suramin acted as a competitive inhibitor of ATP towards both
      Mg2+-ATPase activity and aminophospholipid translocation. However, the inhibition
      of translocation occurred at a higher inhibitor concentration than the inhibition
      of Mg2+-ATPase activity. With elaiophylin, only a partial inhibition of Mg2+
      ATPase activity could be detected, but translocation of labeled
      phosphatidylserine was almost completely abolished. With eosin Y, an almost
      complete inhibition of both Mg2+-ATPase activity and translocation could be
      achieved. The observed responses of aminophospholipid translocation to ATPase
      inhibitors strongly suggest that a P-type ATPase, part of which displays a Mg2+
      ATPase activity, is involved in aminophospholipid translocation.

PMID- 9030723
TI  - Identification and purification of translation initiation factor 2 (IF2) from
      Thermus thermophilus.
AB  - Translation initiation factor 2 (IF2) is one of three protein factors required
      for initiation of protein synthesis in eubacteria. The protein is responsible for
      binding the initiator RNA to the ribosomal P site. IF2 is a member of the GTP GDP
      binding protein superfamily. In the extreme thermophilic bacterium Thermus
      thermophilus, IF2 was identified as a 66-kDa protein by affinity labeling and
      immunoblotting. The protein was purified to homogeneity. The specific activity
      indicates a stoichiometric IF2-mediated binding of formylmethionine-tRNA to 70S
      ribosomes. The N-terminal amino acid sequences of the intact protein and of two
      proteolytic fragments of 25 kDa and 40 kDa were determined. Comparison with other
      bacterial IF2 sequences indicates a similar domain architecture in all bacterial
      IF2 proteins.

PMID- 9030724
TI  - Charge reversal of a critical active-site residue of cytochrome-c peroxidase:
      characterization of the Arg48-->Glu variant.
AB  - A new variant of cytochrome-c peroxidase in which the positively charged Arg48
      present in the distal heme-binding pocket has been replaced with a Glu residue
      has been prepared and characterized to explore, in part, the possibility that a
      negative charge close to the heme could contribute to stabilization of a
      porphyrin-centered pi-cation radical in the compound I derivative of the variant.
      Between pH 4 and 8, this variant forms three pH-linked spectroscopic species. The
      electronic absorption and 1H-NMR spectra of the predominant form at low pH (HS1)
      are indicative of a high-spin, pentacoordinate heme iron system. Near neutral pH,
      a second high-spin species (HS2) is dominant, in which the heme iron center is
      hexacoordinated, with a water molecule as the sixth axial ligand. At high pH, the
      third form (LS) exhibits the spectroscopic characteristics of a low-spin,
      hexacoordinate heme center with bishistidine axial ligation. The apparent pKa
      values for these transitions are 4.4 and 7.4, respectively, in phosphate buffers
      and 5.0 and 7.1, respectively, in phosphate/nitrate buffers. Replacement of Arg48
      with Glu reduces the thermal stability of the enzyme and also decreases the
      Fe(III)/Fe(II) reduction potential of the enzyme by approximately 50 mV relative
      to that of the wild-type enzyme. The stability of compound I formed by the
      variant is decreased although the rate at which it forms is just one order of
      magnitude less than that of the wild-type enzyme, thus confirming previous
      results which indicate that the function of residue 48 in the wild-type
      peroxidase is more related to the stability of compound I than to its formation
      [Erman, J. E., Vitello, L. B., Miller, M. A. & Kraut, J. (1992) J. Am. Chem. Soc.
      114, 6592-6593; Vitello, L. B., Erman, J. E., Miller, M. A., Wang, J. & Kraut, J.
      (1993) Biochemistry 32, 9807-9818]. Stopped-flow studies failed to detect even
      transient formation of a porphyrin-centered radical following addition of
      hydrogen peroxide to the Fe(III)-enzyme. The consequences of this drastic
      electrostatic modification of the active site on the steady-state kinetics of the
      variant are relatively minor.

PMID- 9030725
TI  - Quaternary structure of the extracellular haemoglobin of the lugworm Arenicola
      marina: a multi-angle-laser-light-scattering and electrospray-ionisation-mass
      spectrometry analysis.
AB  - To elucidate the quaternary structure of the extracellular haemoglobin (Hb) of
      the marine polychaete Arenicola marina (lugworm) it was subjected to multi-angle
      laser-light scattering (MALLS) and to electrospray-ionisation mass spectrometry
      (ESI-MS). It was also subjected to SDS/PAGE analysis for comparative purposes.
      MALLS analysis gave a molecular mass of 3648 +/- 24 kDa and a gyration radius of
      11.3 +/- 1.7 nm. Maximum entropy analysis of the multiply charged electrospray
      spectra of the native, dehaemed, reduced and carbamidomethylated Hb forms,
      provided its complete polypeptide chain and subunit composition. We found, in the
      reduced condition, eight globin chains of molecular masses 15952.5 Da (a1),
      15974.8 Da (a2), 15920.9 Da (b1), 16020.1 Da (b2), 16036.2 Da (b3), 16664.8 Da
      (c), 16983.2 Da (d1), 17033.1 Da (d2) and two linker chains L1, 25174.1 Da, and
      L2, 26829.7 Da. In the native Hb, chains b, c, d occur as five disulphide-bonded
      trimer subunits T with masses of 49560.4 Da (T1), 49613.9 Da (T2), 49658.6 Da
      (T3), 49706.8 Da (T4), 49724.5 Da (T5). Linker chains L1 and L2 occur as one
      disulphide-bonded homodimer 2L1 (D1) of 50323.1 Da and one disulphide-bonded
      heterodimer L1-L2 (D2) of 51 981.5 Da. Polypeptide chains a and d possess one
      free cysteine residue and chains d possess an unusual total of five cysteine
      residues. Semi-quantitative analysis of ESI-MS data allowed us to propose the
      following model for the one-twelfth protomer: [(3a1)(3a2)2T] (T corresponding to
      either T3, T4 or T5). From electron micrograph data T1 and T2 are probably
      located at the centre of the molecule as mentioned in previous studies. The Hb
      would thus be composed of 198 polypeptide chains with 156 globin chains and 42
      linker chains, each twelfth being in contact with 3.5 linker subunits, providing
      a total mass of 3682 kDa including haems in agreement with the experimental
      molecular mass determined by MALLS. From ESI-MS relative intensities and the
      model proposed above, the globin/linker ratio gave 0.71:0.29 and 0.73:0.27,
      respectively. The estimation of haem content by pyridine haemochromogen and by
      cyanmethaemoglobin (HiCN) methods also support the globin chain number provided
      by ESI-MS.

PMID- 9030726
TI  - Biochemical and pharmacological characterization of a depressant insect toxin
      from the venom of the scorpion Buthacus arenicola.
AB  - A depressant toxin active on insects, Buthacus arenicola IT2, was isolated from
      the venom of the North African scorpion B. arenicola and its structural and
      pharmacological properties were investigated. B. arenicola IT2 is a single
      polypeptide of 61 amino acid residues, including 8 half-cystines but no
      methionine and histidine, with a molecular mass of 6835 Da. Its amino acid
      sequence is 79-95% identical to other depressant toxins from scorpions. When
      injected into the cockroach Blatella germanica, B. arenicola IT2 induced a slow
      depressant flaccid paralysis with a LD50 of 175 ng. B. arenicola IT2 has two non
      interacting binding sites in cockroach neuronal membranes: one of high affinity
      (Kd1 = 0.11 +/- 0.04 nM) and low capacity (Bmax1 = 2.2 +/- 0.6 pmol/mg), and one
      of low affinity (Kd2 = 24 +/- 7 nM) and high capacity (Bmax2 = 226 +/- 92
      pmol/mg). Its binding to these two sites was completely inhibited by Leiurus
      quinquestriatus quinquestriatus IT2, a depressant toxin from L. quinquestriatus
      quinquestriatus. Reciprocal-binding experiments between B. arenicola IT2 and the
      excitatory insect-toxin A. australis Hector IT revealed competition between the
      two toxins for the high-affinity sites of B. arenicola IT2. B. arenicola IT2 has
      a higher affinity than L. quinquestriatus hebraeus IT2, a depressant toxin from
      L. quinquestriatus hebraeus. Thus, B. arenicola IT2 represents an interesting
      tool to study the receptor site for depressant toxins on insect sodium channels.

PMID- 9030727
TI  - Mutation of amino acids 39-44 of human CD14 abrogates binding of
      lipopolysaccharide and Escherichia coli.
AB  - As a key receptor for lipopolysaccharide (LPS) on the surface of monocytes and
      macrophages, the CD14 molecule is primarily involved in non-specific host defense
      mechanisms against gram-negative bacteria. To delineate the structural basis of
      LPS binding, 23 mutants in the N-terminal 152 amino acids of human CD14 were
      generated and stably transfected into CHO cells. In each mutant, a block of five
      amino acids was substituted by alanine. Reactivity of the mutants with anti-CD14
      mAbs, and their ability to interact with LPS and Escherichia coli were tested. 4
      of 21 expressed CD14 mutants, ([Ala9-Ala13]CD14, [Ala39-Ala41, Ala43, Ala44]CD14,
      [Ala51-Ala55]CD14 and [Ala57, Ala59, Ala61-Ala63]CD14), are not recognized by
      anti-CD14 mAbs that interfere with the binding of LPS to human monocytes.
      However, only [Ala39-Ala41, Ala43, Ala44]CD14 is unable to react with fluorescein
      isothiocyanate-labeled LPS or with FITC-labeled E. coli (055:B5). In addition,
      [Ala39-Ala4l, Ala43, Ala44]CD14 does not mediate LPS (E. coli 055:B5; 10 ng/ml)
      induced translocation of nuclear factor kappaB in CHO-cell transfectants. The
      results indicate that the region between amino acids 39 and 44 forms an essential
      part of the LPS-binding site of human CD14.

PMID- 9030728
TI  - Purified methyl-coenzyme-M reductase is activated when the enzyme-bound coenzyme
      F430 is reduced to the nickel(I) oxidation state by titanium(III) citrate.
AB  - The nickel porphinoid, coenzyme F430, is the prosthetic group of methyl-coenzyme
      M reductase. The active form of the enzyme exhibits Ni-EPR signals designated as
      MCR-red1 and MCR-red2. The inactive form of the enzyme is either EPR silent or it
      exhibits a distinct Ni-EPR signal designated MCR-ox1. Evidence is presented here
      that the MCR-ox1 form of the enzyme can be converted in vitro to the MCR-red1
      form by reduction with titanium(III) citrate at pH 9. During conversion, the
      specific activity increases with increasing MCR-red1 spin concentration from 2
      U/mg to approximately 100 U/mg at spin concentrations higher than 80%. The
      reduced methyl-coenzyme-M reductase shows an ultraviolet/visible spectrum
      characteristic for coenzyme F430 in the Ni(I) oxidation state, with maxima at 386
      nm and at 750 nm. The results indicate that methyl-coenzyme-M reductase is
      activated when the enzyme-bound coenzyme F430 is reduced to the Ni(I) oxidation
      state. The experiments were performed with purified methyl-coenzyme-M reductase
      isoenzyme I of Methanobacterium thermoautotrophicum (strain Marburg).

PMID- 9030729
TI  - Characterization of recombinant perlecan domain I and its substitution by
      glycosaminoglycans and oligosaccharides.
AB  - Recombinant mouse perlecan domain 1(173 residues) was produced in transfected
      embryonic kidney cells and purified from the culture medium on DEAE-cellulose. It
      was shown to be modified by glycosaminoglycans and could be partially separated
      into two protein pools which were either substituted with heparan sulfate
      (fragment IA) or, to a smaller extent (20%), with chondroitin/dermatan sulfate or
      a mixture of both glycosaminoglycans (fragment IB). The average molecular mass of
      the glycosaminoglycans was about 8-10 kDa and, thus, smaller than in tissue
      derived perlecans. Sequence and carbohydrate analyses localized the heparan
      sulfate attachment site to three Ser residues within SGD consensus sequences.
      Furthermore, the N-terminal part of fragment IA contained six Thr/Ser residues
      substituted by branched galactosamine-containing oligosaccharides and an N
      substituted Asn residue. Fragment I was also shown to contain unique
      immunological epitopes which are not dependent on glycosaminoglycans and are
      shared by tissue-derived perlecan. Circular dichroism demonstrated a distinct
      alpha helix (20%) and beta structure (60%) in fragment IA, consistent with
      predictions of a novel SEA protein module located in the C-terminal part of
      domain I.

PMID- 9030730
TI  - The structure of the carbohydrate backbone of the lipopolysaccharide from
      Acinetobacter strain ATCC 17905.
AB  - The structure of the carbohydrate backbone of the lipopolysaccharide from
      Acinetobacter strain ATCC 17905 was studied. After deacylation of the
      lipopolysaccharide, a mixture of two compounds (ratio approximately 2:1) was
      isolated by high-performance anion-exchange chromatography, the structures of
      which were determined by NMR spectroscopy and electrospray-mass spectrometry as
      [STRUCUTRE IN TEXT] [Sug, 3-deoxy-D-manno-2-octulopyranosonic acid (Kdo) in
      oligosaccharide 1 (major portion) and D-glycero-D-talo-2-octulopyranosonic acid
      (Ko) in oligosaccharide 2 (minor portion)]. All monosaccharide residues also
      possess the D-configuration and are present in the pyranose form.

PMID- 9030731
TI  - The effect of platelet-derived growth factor and adipogenic hormones on the
      expression of CCAAT/enhancer-binding proteins in 3T3-L1 cells in serum-free
      conditions.
AB  - In the absence of serum and serum substitutes, insulin at high doses together
      with platelet-derived growth factor BB (PDGF BB), corticosterone, and 3-isobutyl
      1-methyl-xanthine is required to stimulate differentiation of 3T3-L1
      preadipocytes. Under these conditions the differentiating cells express the
      CCAAT/enhancer-binding proteins (C/EBP) C/EBPdelta, C/EBPbeta, and C/EBP alpha
      with a similar sequence as described for differentiating cells in the presence of
      serum. The major differences detected under serum-free conditions are as follows:
      (a) PDGF BB is the major stimulator of the expression of the C/EBPbeta isoform
      liver activator protein (LAP). (b) The expression of LAP is also increased in
      preconfluent, proliferating cells due to the treatment with PDGF BB. (c) A small
      protein of 20 kDa (p20C/EBPbeta is detected with the anti-C/EBPbeta antibody. It
      is synthesized at high levels in such cells, which subsequently express high
      levels of the differentiation markers C/EBP alpha and glycerol-3-phosphate
      dehydrogenase. (d) Treatment of cells with fibroblast growth factor-2 (bFGF) in
      addition to adipogenic hormones results in differentiation and C/EBP alpha
      expression only to a very moderate extent as compared to treatment with PDGF BB
      but leads to a strong expression of both C/EBPbeta and C/EBPdelta.

PMID- 9030733
TI  - Seryl-tRNA synthetase from the extreme halophile Haloarcula marismortui-
      isolation, characterization and sequencing of the gene and its expression in
      Escherichia coli.
AB  - The seryl-tRNA synthetase from the extreme halophilic archaebacterium Haloarcula
      marismortui, belonging to the group Euryarchaeota, has been purified and its
      hyperhalophilic behavior demonstrated by activity and stability tests in KCl,
      NaCl and MgCl2 solutions. Although the natural external environment of this
      archaebacterium is rich in sodium ions and poor in potassium ions, the converse
      being the case in the bacterial cytosol. there is no large significant difference
      in activity and stability in vitro of the enzyme between solutions of NaCl and
      KCl. Low, but not high, concentrations of MgCl2 stabilize the enzyme. The enzyme
      aminoacylates tRNA from Escherichia coli even under the high salt conditions of
      the assay. A fluorescence study indicated that low salt denaturation of the
      hyperhalophilic enzyme is a biphasic process. The hyperhalophilic enzyme
      demonstrated immunological reactivity with antisera against the catalytic domain
      of the homologous E. coli enzyme. The gene coding for the H. marismortui enzyme
      has been isolated and sequenced. The derived amino acid sequence is the first of
      a hyperhalophilic aminoacyl-tRNA synthetase. The wild-type gene and a mutant gene
      with a deletion of the halophile-specific insertion were expressed in E. coli
      using the T7 RNA polymerase and the Thiofusion expression systems. None of the
      expressed proteins were enzymically active. A structural model has been produced
      by comparison with other seryl-tRNA synthetases which illustrates the high
      negative-charge density of the surface of the hyperhalophilic enzyme.

PMID- 9030732
TI  - Distinct efficacies for two endogenous ligands on a single cognate gonadoliberin
      receptor.
AB  - A cDNA encoding a putative gonadoliberin receptor was cloned from the pituitary
      of the African catfish. Conceptual translation predicts a protein of 379 amino
      acids which shows typical characteristics of GTP-binding-protein-coupled
      receptors. The isolated cDNA was stable expressed in human embryonic kidney (HEK)
      293 cells which were used for studies on gonadoliberin-activated second messenger
      systems (inositol phosphate production; increase in cAMP and/or intracellular
      Ca2+). The isolated cDNA encoded a functional receptor, designated catfish
      gonadoliberin receptor (cfGnRH-R), which had an amino acid sequence similarity of
      38% with mammalian gonadoliberin receptors. In contrast to its mammalian
      counterparts which lack an intracellular carboxy-terminal domain, the cfGnRH-R
      contains an additional 49 amino acid residues. From the two endogenous
      gonadoliberins in African catfish, chicken gonadoliberin-II had a several
      hundredfold higher potency than catfish gonadoliberin to activate cfGnRH-R
      associated second messenger systems in transfected HEK 293 cells. This is in line
      with the previously determined higher gonadotropin-release capacity of chicken
      gonadoliberin-II in catfish. Stimulation of second messenger systems with chicken
      gonadoliberin-II, but not with catfish gonadoliberin, resulted in a biphasic
      effect and chicken gonadoliberin-II led to a higher maximum stimulation than
      catfish gonadoliberin. Challenging cfGnRH-R simultaneously with chicken
      gonadoliberin-II and catfish gonadoliberin did not lead to additive effects. In
      contrast, two types of mutual inhibitory effects were recorded. These data
      indicate that a single cognate cfGnRH-R couples with distinct efficacies to
      signal transduction systems upon stimulation by the two endogenous gonadoliberins
      which, in addition, may interact negatively.

PMID- 9030734
TI  - Structural and functional consequences of mutations within the hydrophobic cores
      of the HMG1-box domain of the Chironomus high-mobility-group protein 1a.
AB  - The high-mobility-group protein 1 box domain (HMG1-BD) is a structural element
      found in several DNA-binding proteins in eukaryotic cells. Its structure is
      dominated by three alpha-helices. The spatial arrangement of these helices into
      an L-shaped molecule is maintained by a number of apolar residues organized into
      a main and a secondary hydrophobic core. To analyze the significance of these
      residues for proper folding, conformational stability, and ability to bind and
      bend DNA, we have mutated the highly conserved Trp14 of the Chironomus HMG1a
      protein and have synthesized a series of N-terminally truncated forms. The
      observed alterations in DNA-binding and DNA-bending characteristics were
      correlated with structural consequences, as revealed by CD spectroscopy, limited
      trypsin digestion, and transverse urea gradient gel electrophoresis. Mutation of
      the Trp14 residue (Chironomus [W14A]HMG1a) and deletion of the seven N-terminal
      residues, respectively, which are members of the main and the secondary core of
      Chironomus HMG1a, both resulted in a substantial unfolding of the protein.
      Unexpectedly, these mutants still retained their ability to bind and bend DNA.
      Conformational analysis of wild-type cHMG1a and [W14A]cHMG1a showed that the
      proteins unfold at 2-4 M urea. In contrast, their DNA complexes persisted even at
      6-8 M of the denaturant. Multiple contacts between the HMG1-BD and the DNA are
      probably responsible for the unusual stability of the complexes.

PMID- 9030735
TI  - The surface-dependent autoactivation mechanism of factor XII.
AB  - The dependency of concentrations of Zn2+ and the negatively charged surfaces,
      phosphatidylinositol phosphate (PtdInsP), sulfatide and dextran sulfate, on the
      autoactivation of human factor XII, has been studied. While the autoactivation
      induced by sulfatide, and low concentrations of dextran sulfate, was unaffected
      by the presence of Zn2+, that induced by PtdInsP and higher concentrations of
      dextran sulfate was completely dependent on Zn2+: the excess of Zn2+ needed to
      induce maximal activity with PtdInsP was 12-fold the concentration of factor XII,
      while with dextran sulfate it was 40-fold. Determination of the Zn2+-binding
      properties of factor XII revealed that a total of four zinc ions could bind to
      each factor XII molecule. The first bound zinc ions (Kd 0.1 microM) induced an
      increase in the intrinsic tryptophan fluorescence of factor XII, while further
      titration up to a 40-fold surplus resulted in a quenching of the fluorescence.
      Binding of the zinc ions that caused the quenching had an average Kd of
      approximately 1 microM, independent of whether it was determined from the
      fluorescence changes or by equilibrium filtration. Low concentrations of both
      sulfatide and PtdInsP induced a fluorescence increase similar to that at low
      concentrations of Zn2+ but, in contrast to sulfatide, higher concentrations of
      PtdInsP did not induce a quenching in fluorescence. As the Zn2+-independent
      activating surface (sulfatide) induced quenching in the fluorescence intensity,
      while the Zn2+-dependent activating surface (PtdInsP) did not, the quenching,
      whether it was caused by sulfatide or zinc ions, was assigned to a change in the
      conformation which resulted in a molecular structure of factor XII that could be
      autoactivated. Association of factor XII in this conformation on the activating
      surface was suggested to be responsible for the autoactivation.

PMID- 9030736
TI  - Structural and serological characterisation of the O-specific polysaccharide from
      lipopolysaccharide of Acinetobacter calcoaceticus strain 7 (DNA group 1).
AB  - S-form lipopolysaccharide was isolated by phenol/water extraction from a strain
      of Acinetobacter calcoaceticus (DNA group 1 ). The structure of the O-antigenic
      polysaccharide was determined by compositional analysis and NMR spectroscopy of
      the de-O-acylated lipopolysaccharide. The isolated polysaccharide obtained after
      hydrolysis of lipopolysaccharide in 0.01 M trifluoroacetic acid has the following
      structure: [STRUCTURE IN TEXT] in which Pyr is pyruvate. The O-acetyl
      substitution of D-Gal was non-stoichiometric. The O-antigen was specifically
      recognised in western blots by polyclonal rabbit antisera.

PMID- 9030737
TI  - Modulation of the metarhodopsin I/metarhodopsin II equilibrium of bovine
      rhodopsin by ionic strength--evidence for a surface-charge effect.
AB  - The effects of ionic strength on formation and decay of metarhodopsin II (MII),
      the active photointermediate of bovine rhodopsin, were studied in the native
      membrane environment by means of ultraviolet/ visible and Fourier-transform
      infrared (FTIR) spectroscopy. By increasing the concentration of KCl in the range
      from hypotonic to 4 M, the apparent pKa of the metarhodopsin I(MI)/MII
      equilibrium is shifted by approximately pH three, in favor of the MII
      intermediate. In addition, the apparent rate of MII formation is enhanced by an
      increase in ionic strength (about twofold in the presence of 2 M KCl). MIII decay
      is independent of the salt concentration. Attenuated-total-reflectance/FTIR data
      show that the high-salt conditions have no effect on the rigidity of the membrane
      matrix and do not induce structural changes in the intermediates themselves.
      Different salts were tested for their ability to shift the MI/MII equilibrium;
      however, no clear ion dependence was observed. We interpret these results as an
      indication for direct involvement of the cytosolic surface charge in the
      regulation of the photochemical activity of bovine rhodopsin.

PMID- 9030738
TI  - Biosynthesis of renin in mouse kidney tumor As4.1 cells.
AB  - As4.1, a renin-expressing cell line isolated from a mouse renal tumor, was
      characterized for synthesis, processing, storage and secretion of renin
      polypeptides. Metabolic labeling, immunoprecipitation and SDS/PAGE analysis
      revealed that renin was secreted into the culture supernatant predominantly in
      the form of prorenin which migrated as products of 42-47 kDa. The predominant
      intracellular renin was processed into two chains, of 33-34 and 5 kDa. N
      glycanase treatment removed N-linked oligosaccharides and yielded products of 41
      kDa for prorenin and 31-32 kDa for the heavier chain of two-chain renin. The N
      terminus of the constitutively secreted prorenin was determined by automated
      Edman degradation to be Leu22 while the N-terminus of the heavy chain was Ser72.
      Renin polypeptides constituted 3.1 +/- 1.4% (mean percentage of total
      precipitable radioactivity +/- SD) of de-novo-synthesized protein secreted into
      the medium and 0.2 +/- 0.17% retained intracellularly. Extrapolation of renin
      activity assays suggest that a single cell stores approximately 680 fg of active
      renin. A slow incremental release into the medium of processed renin heavy chain
      was detected by immunoprecipitation and SDS/PAGE. Renin activity assays confirmed
      the release of approximately 4 fg prorenin and 0.32 fg active renin cell(-1) h(
      1). Indirect immunofluorescence demonstrated intracellular renin to be
      distributed in a punctate pattern. Renin was found to be colocalized with the
      lysosomal marker, beta-glucuronidase, by double-fluorescent labeling. These cells
      have enabled characterization of glycosylated mouse renin-1 and may prove a
      valuable tool for studying intracellular trafficing of renin and associated
      processing enzymes.

PMID- 9030739
TI  - Theoretical approaches to the evolutionary optimization of glycolysis:
      thermodynamic and kinetic constraints.
AB  - It is analyzed whether the structural design of contemporary glycolysis can be
      explained theoretically on the basis of optimization principles originating from
      natural selection during evolution. Particular attention is paid to the problem
      of how the kinetic and thermodynamic properties of the glycolytic pathway are
      related to its stoichiometry with respect to the number and location of ATP
      coupling sites. The mathematical analysis of a minimal model of unbranched energy
      converting pathways shows that the requirement of high ATP-production rate
      favours a structural design that includes not only ATP-producing reactions (P
      sites) but also ATP-consuming reactions (C-sites). It is demonstrated that, at
      fixed overall thermodynamic properties of a chain, the ATP-production rate may be
      enhanced by kinetic optimization. The ATP-production rate is increased if the C
      sites are concentrated at the beginning and all the P-sites at the end of the
      pathway. An optimum is attained, which is characterized by numbers of coupling
      sites corresponding to those found in glycolysis. Various extensions of the
      minimal model are considered, which allow the effects of internal feedback
      regulations, variable enzyme concentrations, and the symmetric branching of
      glycolysis at the aldolase step to be considered.

PMID- 9030740
TI  - Processing of thionin precursors in barley leaves by a vacuolar proteinase.
AB  - Thionins are synthesized as precursors with a signal peptide and a long C
      terminal acidic peptide that is post-translationally processed. A fusion protein
      including the maltose-binding protein from Escherichia coli (MalE), thionin DG3
      from barley leaves, and its acidic C-terminal peptide has been used to obtain
      antibodies that recognize both domains of the precursor. In barley leaf sections,
      mature thionins accumulated in the vacuolar content, while the acidic peptide was
      not detected in any cell fraction. Brefeldin A and monensin inhibited processing
      of the precursor but its export from the microsomal fraction was not inhibited.
      Both purified vacuoles and an acid (pH 5.5) extract from leaves processed the
      fusion protein into a MalE-thionin and an acidic peptide fragment. A 70-kDa
      proteinase that effected this cleavage was purified from the acid extract.
      Processing of the fusion protein by both lysed vacuoles and the purified
      proteinase was inhibited by Zn2+ and by Cu2+, but not by inhibitors of the
      previously described vacuolar processing thiol or aspartic proteinases. In vivo
      processing of the thionin precursor in leaf sections was also inhibited by Zn2+
      and Cu2+. Variants of the fusion protein with altered processing sites that
      represented those of thionin precursors from different taxa were readily
      processed by the proteinase, whereas changing the polarity of either the C
      terminal or N-terminal residues of the processing site prevented cleavage by the
      proteinase.

PMID- 9030741
TI  - Identification and structure of activated-platelet protein-1, a protein with RNA
      binding domain motifs that is expressed by activated platelets.
AB  - Beyond their critical role in thrombosis, platelets perform important functions
      in vascular remodeling, inflammation, and wound repair. Many of these functions
      are executed by molecules expressed by activated platelets. A novel molecule,
      activated-platelet protein-1 (APP-1), was identified by a monoclonal antibody
      against activated rabbit platelets. When platelets were stimulated by thrombin,
      A23187 or ADP, APP-I was expressed on the platelet surface. APP-1 was also
      detected in whole cell lysates of platelets, but not on the external surfaces of
      resting platelets. With maximal activation by thrombin, 15 900 +/- 2800 molecules
      APP-1 were expressed/platelet. A 2.3-kb cDNA fragment containing a partial coding
      sequence for APP-1 was isolated from a rabbit bone marrow library by expression
      cloning with the anti-APP-1 monoclonal antibody. When expressed as a recombinant
      fusion protein in bacteria, APP-1 bound specifically to poly(A)-Sepharose. The
      full-length cDNA coding for human APP-1, obtained by DNA hybridization
      techniques, showed 98.7% amino acid sequence identity with the rabbit protein.
      Northern analysis with human APP-1 identified a 3.7-kb mRNA transcript in
      megakaryocytic lines that express transcripts for platelet proteins. Human APP-1
      has four ribonucleotide binding domains with ribonucleoprotein 1 and 2 motifs. By
      virtue of its ribonucleotide binding domains, APP-1 is structurally related to
      polyadenylate-binding protein, which regulates translation initiation and
      polyadenylate shortening, and to nucleolysin, a specific effector molecule found
      in the granules of cytotoxic T lymphocytes.

PMID- 9030742
TI  - Active efflux of the free acid form of the fluorescent dye 2',7'-bis(2
      carboxyethyl)-5(6)-carboxyfluorescein in multidrug-resistance-protein
      overexpressing murine and human leukemia cells.
AB  - Murine and human cell lines overexpressing the multidrug-resistance protein (MRP)
      showed a marked decreased accumulation of the fluorescent dye 2',7'-bis(2
      carboxyethyl)-5(6)-carboxyfluorescein (BCECF). In contrast, less altered
      accumulation was seen in the P-glycoprotein(P-gp)-overexpressing cell lines. The
      decreased drug accumulation was reversed by the energy inhibitors sodium azide/2
      deoxyglucose and by the vinca alkaloid, vincristine, but not by the
      chemotherapeutic agents, etoposide and adriamycin. Decreased accumulation was
      linked to active efflux of the hydrophilic free acid form of BCECF from the MRP
      overexpressing cell lines, indicating that dye extrusion occurs after the dye
      ester has been converted to the free acid form in the cytoplasm. The finding
      suggests that MRP mediates removal of substrates from a cytoplasmic location.
      Buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, decreased
      the vincristine and etoposide resistance displayed by the MRP-expressing murine
      cell lines, but did not affect the accumulation of BCECF. Thus, while glutathione
      may be involved in MRP-mediated resistance to some chemotherapeutic agents, it is
      not necessary for effiux of substrates such as BCECF.

PMID- 9030743
TI  - Purification, structure and in vitro molecular-chaperone activity of Artemia p26,
      a small heat-shock/alpha-crystallin protein.
AB  - Encysted brine-shrimp gastrulae bring their metabolism to a reversible standstill
      during diapause and quiescence, demonstrating a remarkable resistance to
      unfavourable environmental conditions. For example, mortality of Artemia embryos
      under normal temperature and hydration is very low, even after two years of
      anoxia, and embryos commonly experience complete desiccation as part of their
      developmental program. Previous evidence from our laboratories indicated that
      p26, an abundant low-molecular-mass cyst-specific protein capable of
      translocation into the nucleus, may have a protective function in Artemia cysts.
      p26 was purified to apparent homogeneity and a continuous sequence of 141 of its
      amino acids was determined by peptide sequencing, revealing that it is a member
      of the small-heat-shock/alpha-crystallin family of proteins. As determined by
      molecular-sieve chromatography and sucrose-density-gradient centrifugation,
      native p26 is a multimer of about 27 monomers with a molecular mass of
      approximately 700 kDa. Inactivation of citrate synthase was less when the enzyme
      was heated in the presence rather than the absence of p26. Additionally, the
      renaturation of heat-inactivated citrate synthase was promoted by p26. These
      results indicated that p26 possesses molecular-chaperone activity, a property of
      other small heat-shock/alpha-crystallin proteins. Our findings demonstrate that
      p26 has the potential to protect the macromolecular components of Artemia
      embryos, either as they encyst or upon exposure to environmental extremes.
      Protection may depend upon the ability of p26 to function as a molecular
      chaperone.

PMID- 9030744
TI  - Metabolic response in Arenicola marina to limiting oxygen as reflected in the 1H
      NMR oxymyoglobin signal.
AB  - Many intertidal animals can endure prolonged periods of environmental stress and
      have developed strategies to preserve a functioning energy state in the cell.
      Recent 1H/31P-NMR techniques have allowed investigators to monitor directly
      mammalian tissue metabolism in vivo. In particular, the signals of myoglobin (Mb)
      offer a unique opportunity to explore the intracellular oxygen-partial-pressure
      [p(O2)] interaction in Arenicola marina, a standard model to study hypoxia
      tolerance in invertebrates. The present study reveals that the 1H-NMR MbO2 signal
      at -2.9 ppm is detectable in tissue and reflects directly the oxygenated state.
      As the p(O2) declines, MbO2 saturation and oxygen consumption decrease. However,
      phosphotaurocyamine concentration remains unaltered until the MbO2 saturation
      falls below 33%. The extracellular to intracellular p(O2) gradient appears
      substantial. The study establishes the 1H-NMR technique as an approach to measure
      the intracellular p(O2) with an oxygenated state marker and presents the
      interrelationship between oxygen and the metabolic adaptation during hypoxic
      stress.

PMID- 9030745
TI  - The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit
      autophagy in isolated rat hepatocytes.
AB  - Recent studies indicate that phosphatidylinositol 3-kinase is essential in the
      regulation of many processes dependent on membrane flow. Autophagy is a complex
      pathway in which cell material, including proteins, can be degraded. Membrane
      flow plays a pivotal role in this process. To find out whether
      phosphatidylinositol 3-kinase is also required for autophagy, we tested the
      effects on autophagy of two structurally unrelated phosphatidylinositol 3-kinase
      inhibitors, wortmannin and 2-(4-morpholinyl)-8-phenylchromone (LY294002). The
      addition of low concentrations of each of these inhibitors to incubations of
      hepatocytes in the absence of amino acids resulted in a strong inhibition of
      proteolysis. The antiproteolytic effect of wortmannin (IC50 30 nM) and LY294002
      (IC50 10 microM) was accompanied by inhibition of autophagic sequestration and
      not by an increase in lysosomal pH or a decrease in intracellular ATP. No further
      inhibition of proteolysis by the two compounds was observed when autophagy was
      already maximally inhibited by high concentrations of amino acids. 3
      Methyladenine, which is commonly used as a specific inhibitor of autophagic
      sequestration, was an inhibitor of phosphatidylinositol 3-kinase, thus providing
      a target for its action. It is proposed that phosphatidylinositol 3-kinase
      activity is required for autophagy. 3-Methyladenine inhibits autophagy by
      inhibition of this enzyme.

PMID- 9030746
TI  - Effects of spermine and its cytotoxic analogs on nucleosome formation on
      topologically stressed DNA in vitro.
AB  - We investigated the effects of the polyamine spermine and two of its cytotoxic
      analogs 1,11-bis(ethylamino)-4,8-diazaundecane (BE-3-3-3) and 1,19
      bis(ethylamino)-5,10,15-tirazanonadecane (BE-4-4-4-4) on the formation of
      nucleosomes on negatively and positively supercoiled DNA in vitro. Histones H2A,
      H2B, H3 and H4 were reconstituted onto DNA to form nucleosomes and the polyamines
      were added either before or after histone addition. The structural state of the
      nucleosome was monitored by analyzing the DNA topoisomers that were present after
      topoisomerase I treatment. Although polyamines induced DNA aggregation to various
      degrees. high concentrations of topoisomerase I were able to relax the aggregated
      DNA and the helical pitch was found to be unaltered in the aggregates. When
      histones were associated with negatively coiled DNA, the polyamine-induced
      aggregation did not alter nucleosome structure. The induced aggregate did inhibit
      nucleosomal transitions when examined on positively coiled DNA. BE-4-4-4-4 was
      most effective and BE-3-3-3 least effective. These analogs were also extremely
      effective in inhibiting histone deposition onto DNA. A potential mechanism for
      the action of these analogs is both to inhibit histone deposition during DNA
      replication and also disrupt nucleosomal dynamics due to aberrant chromatin
      condensation. These results also suggest that BE-4-4-4-4 and BE-3-3-3 may produce
      their cytotoxic effect through slightly different mechanisms.

PMID- 9030747
TI  - Aspartyl-tRNA synthetase from rat: in vitro functional analysis of its assembly
      into the multisynthetase complex.
AB  - In mammalian cells, nine aminoacyl-tRNA synthetases, including aspartyl-tRNA
      synthetase, are associated within a multienzyme complex. Rat aspartyl-tRNA
      synthetase has a N-terminal polypeptide extension of about 40 amino acid residues
      which can be removed without impairing its catalytic activity. Earlier, in vivo
      studies showed that enzymes deprive of this N-terminal segment behave in vivo as
      free entities. We designed an experimental in vitro approach, based on the
      exchange of the complexed endogenous enzyme by free recombinant species, to
      assess the contribution of that domain in the association of aspartyl-tRNA
      synthetase to the complex. A phosphorylation site was introduced at the N
      terminus of rat aspartyl-tRNA synthetase. The enzyme served as a reporter protein
      to evaluate the dissociation constants of native and N-terminal-truncated species
      towards the complex. Our data show that a moderate but significant drop in
      affinity is inferred by the removal of the N-terminal domain. The results suggest
      that this domain binds to another component of the complex, but might primarily
      serve a targeting function absolutely required in vivo for the assembly within
      the multienzyme structure.

PMID- 9030748
TI  - Mitochondrial asparaginyl-tRNA synthetase is encoded by the yeast nuclear gene
      YCR24c.
AB  - One of the open reading frames located on yeast Saccharomyces cerevisiae
      chromosome III, YCR24c, appeared to code for a protein of unknown function, but
      the predicted sequence showed similarity with asparaginyl-tRNA synthetase from
      Escherichia coli, with 38% amino acid identity. There is a putative mitochondrial
      targeting signal at the N-terminus of the YCR24c product. Northern blot analysis
      of total RNA from a wild-type strain sigma1278b confirmed that YCR24c was
      transcribed. Disruption of the chromosomal copy of YCR24c in a respiratory
      competent haploid cell induced a petite phenotype, but did not affect cell
      viability. This respiratory-defective phenotype is typical for a mutation in a
      nuclear gene that induces a non-functional mitochondrial protein synthesis
      system. The protein encoded by YCR24c was expressed in Escherichia coli in a
      histidine-tagged form and isolated. The enzyme aminoacylated unfractionated
      Escherichia coli tRNA with asparagine. These results identified YCR24c as the
      structural gene for yeast mitochondrial asparaginyl-tRNA synthetase.

PMID- 9030750
TI  - The interactions with solvent, heat stability, and 13C-labelling of alamethicin,
      an ion-channel-forming peptide.
AB  - The peptide alamethicin was labelled with 13C and 15N by growing the fungus
      Trichoderma viride in a medium containing [U-13C] glucose and K15NO3. Spin-echo
      difference spectroscopy showed that 13C was incorporated to a level of about 50%
      and 15N to about 98%. Incorporation of 13C into the peptide provided residue
      specific probes of the interactions with solvent and heat stability of this ion
      channel-forming peptide. All of the carbonyl carbons and the alpha-carbons of the
      alpha-aminoisobutyric acid [Ala(Me)] residues of alamethicin in methanol were
      assigned using two-dimensional and three-dimensional heteronuclear correlation
      experiments. Measurements of 1JC'N revealed hydrogen bonding with solvent at
      residues 1 and 19 at the ends of the peptide and at Gly11 in the middle. The data
      also support the thesis [see Juranic, N., Ilich, P. K. & Macara, S. (1995) J. Am.
      Chem. Soc. 117, 405-410 that intramolecular hydrogen bonds in proteins and
      peptides are weaker than hydrogen bonds to solvent. The sensitivity of
      alamethicin carbonyl and proton chemical shifts to perturbation by dimethyl
      sulfoxide correlates well with the calculated solvent accessibilities of the
      carbonyls in the crystal structures and reveals residues in the middle of the
      peptide and at the C-terminus which interact with solvent. Taken together with
      the 1JC'N measurements, the data support a model in which hydrogen bonding to
      solvent at the Gly11/Leu12 amide could provide a site of hydration in the
      interior of the alamethicin channel structure. The temperature dependencies of
      the carbonyl chemical shifts support the suggestion that the peptide is flexible
      in the regions where solvent interacts with the backbone of the peptide. The
      linear temperature dependence of the carbonyl chemical shifts and molar
      ellipticity indicate that, due to steric constraints at the Ala(Me) residues, the
      peptide folding/unfolding transition is non-cooperative and that the peptide is
      remarkably heat stable.

PMID- 9030749
TI  - Study of non-covalent enzyme-inhibitor complexes of aldose reductase by
      electrospray mass spectrometry.
AB  - Specific non-covalent interactions between aldose reductase (AR), its NADP+
      cofactor and five inhibitors have been characterized by electrospray mass
      spectrometry (ES-MS). These results indicated that the protein could be desorbed
      and maintained in the gas phase in a form very close to its native conformation.
      Collisionally induced dissociation (CID)-MS and CID-MS-MS showed that the
      adenosine diphosphate part of the cofactor interacts strongly with AR. The
      relative stability of the ternary AR x NADP+ x inhibitor complexes was
      established and successfully correlated with the IC50 values. All inhibitors were
      shown to only bind to AR holoenzyme. These results are important for the field of
      drug development insofar as ES-MS might provide a rapid and very sensitive method
      for the screening of potential drugs or for the identification of compounds
      displaying high binding affinity to a target biomolecule.

PMID- 9030751
TI  - 1H-NMR study of inter-segmental hydrogen bonds in sperm whale and horse
      apomyoglobins.
AB  - NMR signals for HisB5 N(delta)H and HisEF5 N(epsilon)H protons of sperm whale and
      horse apomyoglobins were assigned and compared with the corresponding signals of
      the holoproteins in terms of pH and temperature dependence behaviors of their
      shifts and line widths in order to gain insight into structural difference
      between the apoproteins and the holoproteins. Since these protons are involved in
      internal hydrogen bonds at the interfaces between the B helix and the GH corner
      and between the EF corner and the H helix, local structures of the interfaces in
      these proteins have been inferred from the analyses of these signals. A large
      difference in the line width of HisEF5 N(epsilon)H proton signal between the
      apoproteins and the holoproteins strongly suggested that a sizable structural
      alteration is induced in the EF-H interface by the removal of heme. However, the
      results for HisB5 N(delta)H proton resonance indicated the absence of a
      significant structural alteration in the B-GH interface by heme extraction. These
      results are consistent with the data obtained from mutation [Hughson, F. M. &
      Baldwin, R. L. (1989) Biochemistry 28, 4415-4422] and amide-proton-exchange
      kinetic [Hughson, F. M., Wright, P. E. & Baldwin, R. L. (1990) Science 249, 1544
      1548] studies, which indicated that the A, B, G and H helices in apomyoglobin
      maintain the same packing as they do in holoprotein.

PMID- 9030752
TI  - Investigation of two glycosylated forms of bile-salt-dependent lipase in human
      pancreatic juice.
AB  - Pure human pancreatic bile-salt-dependent lipase, devoid of its oncofetal
      glycoform [Mas, E., Abouakil, N., Roudani, S., Miralles, F., Guy-Crotte., O.,
      Figarella, C., Escribano, M. J. & Lombardo, D. (1993) Biochem. J. 289, 609-615],
      was analyzed on immobilized concanavalin A (ConA). Two variants were separated:
      an unabsorbed ConA-unreactive fraction; and an absorbed ConA-reactive fraction.
      Carbohydrate compositions of ConA-reactive and ConA-unreactive fractions were not
      significantly different, and analysis of 3H-labelled oligosaccharides liberated
      from these fractions on the ConA-Sepharose column indicated that the
      fractionation of the bile-salt-dependent lipase on this column depends upon
      oligosaccharide structures. The activity of the ConA-reactive fraction was
      however much lower, independent of the substrate (4-nitrophenyl hexanoate or
      cholesteryl esters), than that of the ConA-unreactive fraction. Therefore,
      catalytic constants for the hydrolysis of 4-nitrophenyl hexanoate were
      determined; both fractions had quite similar Km, while the kcat for the ConA
      unreactive fraction was 3-4-fold higher than that of the ConA-reactive fraction.
      ConA-reactive and ConA-unreactive fractions were shown to have slightly different
      molecular masses and different amino acid compositions. Cleavage patterns after
      cyanogen bromide treatment of the ConA-reactive and ConA-unreactive fractions
      suggested that the ConA-reactive (high Mr form) and ConA-unreactive (low Mr form)
      forms could be different isoforms of the bile-salt-dependent lipase secreted by
      the human pancreas.

PMID- 9030753
TI  - The fructose transporter of Bacillus subtilis encoded by the lev operon: backbone
      assignment and secondary structure of the IIB(Lev) subunit.
AB  - The fructose transporter of the Bacillus subtilis phosphotransferase system
      consists of two membrane associated (IIA and IIB) and two transmembrane (IIC and
      IID) subunits [Martin-Verstraete, I., Debarbouille, M., Klier, A. & Rapoport, G.
      (1990) J. Mol. Biol. 214, 657-671] . It mediates uptake by a mechanism which
      couples translocation to phosphorylation of the transported solute. The 18-kDa
      IIBLev subunit transfers phosphoryl groups from His9 of the IIA subunit to the
      sugar. The three-dimensional structure of IIBLev or similar proteins is not
      known. IIBLev was overexpressed in Escherichia coli and isotopically labelled
      with 13C/15N in H2O as well as in 70% D2O. 15N-edited NOESY, 13C-edited NOESY and
      13C,15N triple-resonance experiments yielded a nearly complete assignment of the
      1H, 13C and 15N resonances. Based on qualitative interpretation of NOE, scalar
      couplings, chemical shift values and amide exchange data, the secondary structure
      and topology of IIBLev was determined. IIBLev comprises six parallel beta
      strands, one antiparallel beta-strand and 5 alpha-helices. The order of the major
      secondary-structure elements is (beta alpha)5beta (strand order 7651423).
      Assuming that the (beta alpha beta)-motives form right-handed turn structures,
      helices alphaA and alphaB are packed to one face and helices alphaC, alphaD and
      alphaE to the opposite face of the parallel beta-sheet. His15 which is
      transiently phosphorylated during catalysis is located in the loop beta1/alphaA
      of the topological switch point. The amino terminal (beta/alpha)4 part of IIBLev
      has the same topology as phosphoglyceromutase (PGM; PDB entry 3pgm). Both
      proteins catalyze phosphoryltransfer reactions which proceed through
      phosphohistidine intermediates and they show a similar distribution of invariant
      residues in the topologically equivalent positions of their active sites. The
      protein fold of IIBLev has no similarity to any of the known structures of other
      phosphoenolpyruvate-dependent-carbohydrate-phosphotransferase-system proteins.

PMID- 9030754
TI  - Purification and characterization of an endo-1,3-beta-glucanase from Aspergillus
      fumigatus.
AB  - An endo-1,3-beta-glucanase was purified from a cell wall autolysate of
      Aspergillus fumigatus. This beta-glucanase activity was associated with a
      glycosylated 74-kDa protein. Using a sensitive colorimetric assay and a high
      performance anion-exchange chromatography with a pulsed electrochemical detector
      for product analysis, it was shown that the endoglucanase hydrolysed exclusively
      linear 1,3-beta-glucan chains, had an optimum pH of 7.0 and an optimum
      temperature of 60 degrees C. A substrate kinetic study gave a Km value of 0.3
      mg/ml for soluble (laminarin and laminari-oligosaccharides) and 1.18 mg/ml for
      insoluble (curdlan) 1,3-beta-glucan. Laminari-oligosaccharide degradation,
      analysed by HPLC, showed that the endoglucanase bind to the subtrate at several
      positions and suggested that the active site of the enzyme recognized five
      glucose units linked by a 1,3-beta bond. The association of the present endo-1,3
      beta-glucanase with the cell wall of A. fumigatus suggests a putative role for
      this enzyme during cell-wall morphogenesis.

PMID- 9030755
TI  - Imidase, a dihydropyrimidinase-like enzyme involved in the metabolism of cyclic
      imides.
AB  - Imidase, which preferably hydrolyzed cyclic imides to monoamidated
      dicarboxylates, was purified to homogeneity from a cell-free extract of
      Blastobacter sp. A17p-4. Cyclic imides are known to be hydrolyzed by mammalian
      dihydropyrimidinases. However, imidase was quite different from known
      dihydropyrimidinases in structure and substrate specificity. The enzyme has a
      relative molecular mass of 105 000 and consists of three identical subunits. The
      purified enzyme showed higher activity and affinity toward cyclic imides, such as
      succinimide (Km = 0.94 mM; Vmax = 910 micromol x min(-1) x mg(-1)), glutarimide
      (Km = 4.5 mM; Vmax = 1000 micromol min (-1) x mg (-1) and maleimide (Km = 0.34
      mM; Vmax = 5800 micromol x min(-1)x mg(-1)), than toward cyclic ureides, which
      are the substrates of dihydropyrimidinases, such as dihydrouracil and hydantoin.
      Sulfur-containing cyclic imides, such as 2,4-thiazolidinedione and rhodanine,
      were also hydrolyzed. The enzyme catalyzed the reverse reaction, cyclization, but
      with much lower activity and affinity. The enzyme was non-competitively inhibited
      by succinate, which was found to be a key compound in cyclic-imide transformation
      in relation with the tricarboxylic acid cycle in this bacterium, suggesting that
      the role of imidase is to catalyze the initial step of cyclic-imide degradation.

PMID- 9030756
TI  - Changes in cellular and plasma membrane phospholipid composition after
      lipopolysaccharide stimulation of human neutrophils, studied by 31P NMR.
AB  - Lipopolysaccharide (endotoxin, LPS) exerts potent proinflammatory effects on
      neutrophils which may involve membrane phospholipid metabolism. The cellular and
      plasma membrane phospholipid composition of resting neutrophils and those
      stimulated with 50 microg ml(-1) LPS were studied by 31P NMR and chemical
      analysis. A rapid new method for plasma membrane purification was employed,
      involving the direct lysis of cytoplasts. Chemical analyses showed that, although
      total cellular phospholipid content did not change with LPS stimulation, there
      was twice the amount of phospholipid present in plasma membranes isolated from
      stimulated cells, resulting in a lowered cholesterol/phospholipid ratio. Since
      internal membranes have lower cholesterol content this result is consistent with
      an origin from insertion of these membranes (most probably from the endoplasmic
      reticulum) into the plasma membrane, thereby increasing its fluidity. The
      individual phospholipid classes of both cells and membranes were quantified by
      31P-NMR spectroscopy after dissolution in sodium cholate without prior extraction
      of lipids, allowing partial resolution of the major phospholipid classes and
      ether-linked phospholipids. Ether-linked lipids were distinguished from diacyl
      phospholipids by hydrolysis of lipid extracts with HCl and phospholipase A1,
      There was a significant increase in phosphatidylserine in both cells and plasma
      membranes after stimulation, with a decrease in the phosphatidylethanolamine
      (diacyl and plasmalogen) content in the cells. Plasma membranes from stimulated
      cells exhibited a significant decrease in a phospholipid tentatively identified
      as 2-arachidonoyl-1-alkyl-sn-glycero-3-phosphocholine, a precursor of the lipid
      inflammatory mediator, platelet-activating factor. This report is the first to
      elaborate the changes in phospholipid composition in human neutrophils as a
      whole, and in plasma membranes separated from them, before and after stimulation
      by the physiological activator, LPS.

PMID- 9030757
TI  - Turnover number of Escherichia coli F0F1 ATP synthase for ATP synthesis in
      membrane vesicles.
AB  - The rate of ATP synthesized by the ATP synthase (F0F1-ATPase) is limited by the
      rate of energy production via the respiratory chain, when measured in everted
      membrane vesicles of an Escherichia coli atp wild-type strain. After energization
      of the membranes with NADH, fractional inactivation of F0F1 by the covalent
      inhibitor N,N'-dicyclohexylcarbodiimide allowed the rate of ATP synthesis/mol
      remaining active ATP synthase complexes to increase; the active ATP synthase
      complexes were calculated using ATP hydrolysis rates as the defining parameter.
      In addition, variation of the assay temperature revealed an increase of the ATP
      synthesis rate up to a temperature of 37 degrees C, the optimal growth
      temperature of E. coli. In parallel, the amount of F0F1 complexes present in
      membrane vesicles was determined by immunoquantitation to be 3.3 +/- 0.3% of the
      membrane protein for cells grown in rich medium and 6.6 +/- 0.3% for cells grown
      in minimal medium with glycerol as sole carbon and energy source. Based on these
      data, a turnover number for ATP synthesis of 270 +/- 40 s(-1) could be determined
      in the presence of 5% active F0F1 complexes. Therefore, these studies demonstrate
      that the ATP synthase complex of E. coli has, with respect to maximum rates, the
      same capacity as the corresponding enzymes of eukaryotic organells.

PMID- 9030758
TI  - Characterization of two vaccinia CD36 recombinant-virus-generated monoclonal
      antibodies (10/5, 13/10): effects on malarial cytoadherence and platelet
      functions.
AB  - Extensive evidence is now available to show that the human CD36 antigen is a
      cellular receptor for thrombospondin, collagen, modified low-density
      lipoproteins, and long-chain fatty acids. Moreover, CD36 functions as one of the
      receptors that mediates the adhesion of Plasmodium-falciparum-infected
      erythrocytes to microvascular endothelium. In an attempt to identify new
      functional sites of this surface glycoprotein, anti-CD36 monoclonal antibodies
      were prepared using a vaccinia CD36 recombinant virus as a highly efficient
      immunization vector. In functional studies, one of these antibodies (clone 10/5)
      strongly inhibited the adhesion of P. falciparum-infected erythrocytes to
      purified CD36. This antibody also potentiated ADP-induced platelet activation. In
      contrast, a second antibody (clone 13/10) did not affect the cytoadherence of
      infected erythrocytes or platelet functions. Previous structural work performed
      on these antibodies has shown that clone 10/5 is directed against an epitope
      within the CD36 domain 155-183, whereas clone 13/10 interacts with another
      antigenic determinant defined by amino acids 30-76 [Daviet, L., Buckland, R.,
      Puente Navazo, M. D. & McGregor, J. L. (1995) Biochem. J. 305, 221-224]. Taken
      together, these current studies show that: (a) the methodology of immunization
      using recombinant vaccinia virus is a powerful tool in the generation of
      monoclonal antibodies directed against polyimmunogenic membrane glycoproteins
      such as CD36; (b) the CD36 domain, recognized by clone 10/5 but not by 13/10, is
      functionnally important regarding the adhesion of P. falciparum-infected
      erythrocyte and CD36-dependent platelet activation.

PMID- 9030759
TI  - The wheat poly(A)-binding protein functionally complements pab1 in yeast.
AB  - Poly(A)-binding protein (PAB) binds to the poly(A) tail of most eukaryotic mRNAs
      and influences its translational efficiency as well as its stability. Although
      the primary structure of PAB is well conserved in eukaryotes, its functional
      conservation across species has not been extensively investigated. In order to
      determine whether PAB from a monocot plant species could function in yeast, a
      protein characterized as having PAB activity was purified from wheat and a cDNA
      encoding for PAB was isolated from a wheat seedling expression library. Wheat PAB
      (72 kDa as estimated by SDS/PAGE and a theoretical mass of 70 823 Da as
      determined from the cDNA) was present in multiple isoforms and exhibited binding
      characteristics similar to that determined for yeast PAB. Comparison of the wheat
      PAB protein sequence with PABs from yeast and other species revealed that wheat
      PAB contained the characteristic features of all PABs, including four RNA binding
      domains each of which contained the conserved RNP1 and RNP2 sequence motifs. The
      wheat PAB cDNA functionally complemented a pab1 mutant in yeast suggesting that,
      although the amino acid sequence of wheat PAB is only 47% conserved from that of
      yeast PAB, this monocot protein can function in yeast.

PMID- 9030760
TI  - Cooperative amplification of templates by cross-hybridization (CATCH).
AB  - In vitro amplification systems not only serve as a tool for the processing of
      DNA, but have also provided important model systems for the investigation of
      fundamental issues in evolutionary optimization. In this work we present a
      coupled amplification system based on the self-sustained sequence replication
      (3SR), also known as nucleic acid sequence-based amplification (NASBA), which
      allows the experimental investigation of evolving molecular cooperation. The 3SR
      reaction is an isothermal method of nucleic acid amplification and an alternative
      to PCR. A target nucleic acid sequence can be amplified exponentially in vitro
      using two enzymes: reverse transcriptase (RT) and a DNA-dependent RNA polymerase
      (RNAP). A system has been constructed in which amplification of two molecular
      species is cooperatively coupled. These species are single-stranded (ss)DNA
      templates (D1 and D2) of lengths 58 and 68 nucleotides, respectively. Coupling
      occurs when D1 and D2 anneal to each other via a complementary region (DB and
      DB') situated at the 3' end of each template. RT elongates the hybridized
      templates producing a double-stranded (ds)DNA of 106 base pairs (bp). This double
      strand contains two promoters, which are situated on either side of, and directly
      adjacent to DB, and which are oriented towards each other. These promoters
      specify two RNA transcripts encompassing, respectively, the D1 and D2 portion of
      the dsDNA. After hybridization of two primers (P1 and P2) to the transcripts (R1
      and R2) and reverse transcription, the ss templates D1 and D2 are regenerated.
      Amplification cycles of D1 and D2 are coupled cooperatively via the common dsDNA
      intermediate. Under optimized batch conditions the system shows the expected
      growth phases: exponential, linear and saturation phase. The enzymes of the 3SR
      cycle tend to misincorporate nucleotides and to produce abortive products. In
      future experiments, we intend to use the system for studies of evolutionary
      processes in spatially distributed systems where new strategies for optimization
      at the molecular level are possible.

PMID- 9030761
TI  - Recombinant [Phe(beta)63]hemoglobin shows rapid oxidation of the beta chains and
      low-affinity, non-cooperative oxygen binding to the alpha subunits.
AB  - We have engineered alpha2beta2 [Phe63]hemoglobin by changing the highly conserved
      distal histidine of the beta chains to a phenylalanine. The mutant tetramer binds
      four high-affinity ligands, such as CO or NO, to the ferrous form, or CN to the
      oxidized iron; however, it binds only two low-affinity ligands, oxygen and azide.
      The absorption spectrum of the ferrous deoxy or ferric forms are not normal,
      displaying an enhanced absorption of the visible band near 560 nm. Half of the
      autooxidation process, attributed to the mutated beta subunits, is over 1000-fold
      faster than for Hb A. The mutant Hb exhibits non-cooperative binding of two
      oxygens with an affinity about fivefold lower than those of HbA valency hybrids
      (alpha met beta)2. Functional properties of this mutant Hb resemble those of Hb
      Saskatoon ([Tyr63]Hb) [Suzuki, T., Hayashi, A., Shimizu, A. & Yamamura, Y. (1966)
      Biochim. Biophys. Acta 127, 280-282]. Flash-photolysis experiments also indicate
      non-cooperative behaviour: the CO-recombination kinetics were independent of the
      fraction dissociated. Furthermore, the amplitude of the CO bimolecular phase was
      the same for the (alpha(CO)metbeta)2 valency hybrid or the (alphaCO betaCO)2
      form, suggesting mainly geminate CO-recombination kinetics to the beta chains.
      EPR and Resonance Raman spectra did not show evidence for a hemichrome, normally
      considered as a six-coordinated iron with low-spin character. The EPR and
      resonance Raman spectra for the mutated beta subunits demonstrate the presence of
      a high-spin compound in the ferric and deoxy ferrous forms. In particular, the
      ferrous mutated beta subunits are penta-coordinated. The abnormal absorption
      spectra are possibly due to an interaction between the porphyrin and the phenyl
      ring in the distal position rather than to direct binding to the iron.

PMID- 9030762
TI  - NMR solution structure of an oxidised thioredoxin h from the eukaryotic green
      alga Chlamydomonas reinhardtii.
AB  - NMR solution structures of a cytosolic plant thioredoxin h (112 amino acids, 11.7
      kDa) from the green alga Chlamydonmonas reinhardtii have been calculated on the
      basis of 1904 NMR distance restraints, which include 90 distances used to
      restrain 45 hydrogen bonds, and 44 phi dihedral restraints. The structure of C.
      reinhardtii thioredoxin h was solved in its oxidised form, and the ensemble of 23
      converged structures superpose to the geometric average structure with an atomic
      rmsd of 0.080 nm +/- 0.016 for the (N, C(alpha), C) backbone atoms of residues 4
      110. Comparisons with other thioredoxins, such as thioredoxin from the bacterium
      Escherichia coli, thioredoxin 2 from a cyanobacterium of the Anabaena genus, and
      human thioredoxin, showed that thioredoxin h models share more structural
      features with human thioredoxin than with other bacterial thioredoxins.
      Examination of the accessible surface around the redoxactive peptide sequence
      indicates that a potent thioredoxin-h-substrate interaction could be similar to
      the vertebrate thioredoxin-substrate interactions.

PMID- 9030763
TI  - Characterisation of the isolated Che Y C-terminal fragment (79-129)--Exploring
      the structure/stability/folding relationship of the alpha/beta parallel protein
      Che Y.
AB  - To gain insight into how the three-dimensional structure, stability and folding
      of the protein Che Y are related to one another, we have performed a
      conformational analysis of a long fragment of this protein, encompassing its C
      terminal 51 residues (79-129). This fragment consists of residues in the beta
      strands 4 and 5 and alpha-helices 4 and 5 of native Che Y. The study has been
      performed by two-dimensional NMR and far-ultraviolet circular dichroism in
      aqueous solution and in 30% (by vol.) trifluoroethanol/ water at 273 K and 298 K.
      We observe little structure for this fragment in aqueous solution which could be
      due to low helical populations in the regions corresponding to helices 4 and 5.
      Within the limits of the residual helical structure experimentally detected,
      helix 4 appears to extend beyond the N-terminus observed in the native structure
      by over four residues belonging to the preceding loop. In 30% trifluoroethanol
      the helical content of both helices increase and helix 4 extends further to
      include the preceding beta-strand 4. None of the long-range NOEs present in
      native Che Y are observed under the explored experimental conditions. The
      conformational shifts of the H(alpha) protons within the alpha-helices of
      fragment 79-129 are identical to those of shorter synthetic peptides
      corresponding to the isolated alpha-helices. Thus, the fragment 79-129 appears to
      behave as an open chain with low local helical populations. The very low
      intrinsic ability for structure formation displayed by this region of Che Y at pH
      2.5 suggests that in the folded protein this region could be mainly stabilised by
      interactions with the N-terminal Che Y region. This is in accordance with the
      contact map of Che Y, which shows that the strongest non-local contacts of C
      terminal residues are with residues of the N-terminal region, while those within
      the C-terminal region are very weak. More importantly, the relationship appears
      to be possibly extended to the folding properties of the protein, since the C
      terminal region is not structurally formed in the folding transition state of Che
      Y but in the final steps of the folding.

PMID- 9030764
TI  - An ultracentrifugal approach to quantitative characterization of the molecular
      assembly of a physiological electron-transfer complex: the interaction of
      electron-transferring flavoprotein with trimethylamine dehydrogenase.
AB  - The interaction between two physiological redox partners, trimethylamine
      dehydrogenase and electron-transferring flavoprotein, has been characterized
      quantitatively by analytical ultracentrifugation at 4 degrees C. Analysis of
      sedimentation-equilibrium distributions obtained at 15 000 rpm for mixtures in 10
      mM potassium phosphate, pH 7.5, by means of the psi function [Wills, P. R.,
      Jacobsen, M. P. & Winzor, D. J. (1996) Biopolymers 38, 119-130] has yielded an
      intrinsic dissociation constant of 3-7 microM for the interaction of electron
      transferring flavoprotein with two equivalent and independent sites on the
      homodimeric enzyme. This investigation indicates the potential of sedimentation
      equilibrium for the quantitative characterization of interactions between
      dissimilar macromolecules.

PMID- 9030765
TI  - Spectroscopic studies of the C-terminal secretion signal of the Serratia
      marcescens haem acquisition protein (HasA) in various membrane-mimetic
      environments.
AB  - The structure of a peptide comprising the last 56 C-terminal residues of the
      Serratia marcescens haem acquisition protein (HasA) secreted by an ATP-binding
      cassette exporter was examined by 1H-NMR, circular dichroic and fluorescence
      spectroscopies. The peptide, which contains the secretion signal of HasA, is
      efficiently secreted by the HasA transporter. It is largely unstructured and
      flexible in aqueous buffer solution, but its helical content increases upon
      addition of trifluoroethanol, detergents and lipids. By circular dichroism, a
      stable helical conformation is observed between 20% and 70% (by vol.)
      trifluoroethanol. The 1H-NMR spectrum was analysed at these two trifluoroethanol
      concentrations; residues 7-15, 21-30 and 40-50 were shown to form relatively
      stable helices. In the presence of neutral detergent, alpha-helix is induced to a
      similar extent upon micelle formation; in this case, fluorescence data indicate
      that at least the N-terminus of the peptide interacts with the micelle. In the
      presence of negatively charged detergent, alpha-helix is induced before micelle
      formation and the N-terminus of the peptide seems not to be involved in this
      interaction. In the presence of negatively charged liposomes, the peptide
      interacts with the vesicle, again inducing a helical conformation. However, the
      helical content remains lower than upon addition of trifluoroethanol or neutral
      micelles. These results are compared to those previously obtained with the
      secretion signal of one of the Erwinia chrysanthemi metalloproteases which are
      transported efficiently by the HasA transporter. Both signals exhibit similar
      conformational features, despite their low sequence similarity.

PMID- 9030766
TI  - Nicotinamide riboside, an unusual, non-typical, substrate of purified purine
      nucleoside phosphorylases.
AB  - Nicotinamide 1-beta-D-riboside (Nir), the cationic, reducible moiety of the
      coenzyme NAD+, has been confirmed as an unusual substrate for purified purine
      nucleoside phosphorylase (PNP) from a mammalian source (calf spleen). It is also
      a substrate of the enzyme from Escherichia coli. The Km values at pH 7, 1.48 mM
      and 0.62 mM, respectively, were 1-2 orders of magnitude higher than for the
      natural substrate inosine, but the Vmax values were comparable, 96% and 35% that
      for Ino. The pseudo first-order rate constants, Vmax/Km, were 1.1% and 2.5% for
      the calf spleen and E. coli enzymes. The aglycon, nicotinamide, was neither a
      substrate nor an inhibitor of PNP. Nir was a weak inhibitor of inosine
      phosphorolysis catalyzed by both enzymes, with Ki values close to the Km for its
      phosphorolysis, consistent with simple competitive inhibition; this was further
      confirmed by Dixon plots. Phosphorolysis of the fluorescent positively charged
      substrate 7-methylguanosine was also inhibited in a competitive manner by both
      Ino and Nir. Phosphorolysis of Nir by both enzymes was inhibited competitively by
      several specific inhibitors of calf spleen and E. coli PNP, with Ki values
      similar to those for inhibition of other natural substrates. The pH dependence of
      the kinetic constants for the phosphorolysis of Nir and of a variety of other
      substrates, was extensively investigated, particularly in the alkaline pH range,
      where Nir exhibited abnormally high substrate activity relative to the reduced
      reaction rates of both enzymes towards other anionic or neutral substrates. The
      overall results are discussed in relation to present concepts regarding binding
      and phosphorolysis of substrates by PNP based on crystallographic data of enzyme
      inhibitor complexes, and current studies on enzymatic and nonenzymatic mechanisms
      of the cleavage of the Nir glycosidic bond.

PMID- 9030767
TI  - A small-angle neutron scattering study of gamma-crystallins near their
      isoelectric point.
AB  - In this paper, a small-angle neutron scattering study of gammaII-crystallins near
      their isoelectric point is presented. The experiments were carried out using
      protein concentrations of 5.7-85.7 mg/ml at temperatures in the range 11 -60
      degrees C. The experimental data were analyzed using an ellipsoidal model for
      intraparticle correlations and the mean spherical approximation for interparticle
      correlations. Our studies revealed that gammaII-crystallins have a thick
      hydration layer, which is possibly due to the special arrangement of polar and
      ionic groups on their surface. The temperature scan shows that, as a result of
      relatively strong attractive forces, clusters of two, three, or higher oligomers
      are present below 20 degrees C. Our results suggest that protein clusters, with a
      distinctive hydration layer, form a protein-rich phase that separates from a
      protein-lean phase as the temperature is decreased below some threshold value.

PMID- 9030768
TI  - Isolation and biochemical characterisation of monomeric and dimeric photosystem
      II complexes from spinach and their relevance to the organisation of photosystem
      II in vivo.
AB  - Membranes enriched in photosystem II were isolated from spinach and further
      solubilised using n-octyl beta-D-glucopyranoside (OctGlc) and n-dodecyl beta-D
      maltoside (DodGlc2). The OctGlc preparation had high rates of oxygen evolution
      and when subjected to size-exclusion HPLC and sucrose density gradient
      centrifugation, in the presence of DodGlc2, separated into dimeric (430 kDa),
      monomeric (236 kDa) photosystem II cores and a fraction containing photosystem II
      light-harvesting complex (Lhcb) proteins. The dimeric core fraction was more
      stable, contained higher levels of chlorophyll, beta-carotene and plastoquinone
      per photosystem II reaction centre and had a higher oxygen-evolving activity than
      the monomeric cores. Their subunit composition was similar (CP43, CP47, D1, D2,
      cytochrome b 559 and several lower-molecular-mass components) except that the
      level of 33-kDa extrinsic protein was lower in the monomeric fraction. Direct
      solubilisation of photosystem-II-enriched membranes with DodGlc2, followed by
      sucrose density gradient centrifugation, yielded a super complex (700 kDa)
      containing the dimeric form of the photosystem II core and Lhcb proteins: Lhcb1,
      Lhcb2, Lhcb4 (CP29), and Lhcb5 (CP26). Like the dimeric and monomeric photosystem
      II core complexes, the photosystem II-LHCII complex had lost the 23-kDa and 17
      kDa extrinsic proteins, but maintained the 33-kDa protein and the ability to
      evolve oxygen. It is suggested, with a proposed model, that the isolated
      photosystem II-LHCII super complex represents an in vivo organisation that can
      sometimes form a lattice in granal membranes of the type detected by freeze-etch
      electron microscopy [Seibert, M., DeWit, M. & Staehelin, L. A. (1987) J. Cell
      Biol. 105, 2257-2265].

PMID- 9030769
TI  - Energy-filtered electron microscopy reveals that talin is a highly flexible
      protein composed of a series of globular domains.
AB  - Talin is a multidomain cytoskeletal protein containing discrete binding sites for
      acidic phospholipids, beta-integrin, actin and vinculin. Hence, it is thought to
      link microfilaments to the cytoplasmic membrane in cell-matrix adhesion sites,
      and this should critically depend on talin structure. To obtain more information
      on the latter, we used energy-filtered transmission electron microscopy of
      negatively stained talin purified from chicken smooth muscle. We show that in
      buffers of physiological ionic strength, talin adopts an elongated shape (56 +/-
      7 nm in length), consisting of a series of globular masses. While these compact
      elements, arranged like beads on a string, were of rather uniform dimensions (3.8
      nm in diameter), their center-to-center spacings varied, indicating the
      flexibility of the connecting strands. The ends of the elongated molecules
      frequently formed loops. The images obtained are consistent with the assumption
      that, under the conditions used, the majority of the talin molecules are
      monomeric. A minor fraction appeared as dimers, composed of two chains only
      partially intertwined, thus giving rise to Y-shaped particles. Electron
      micrographs revealed that the biochemically defined 50-kDa N-terminal talin head
      domain is composed of two globular subunits, while chemical cross-linking
      provided evidence that the C-terminal 220-kDa fragment is solely responsible for
      dimerization. These results imply that in the dimeric molecules, the polypeptide
      chains are arranged in parallel, in contrast to what has been described for human
      platelet talin. In buffers of low ionic strength (0.02 M instead of 0.15 M KCl),
      the molecules collapsed into a compact shape. By showing the high flexibility and
      versatility of its morphology, our data favour the concept of talin as an
      important resilient link in microfilament-plasma-membrane attachment.

PMID- 9030770
TI  - Primary structure of EPV20, a secretory glycoprotein containing a previously
      uncharacterized type of domain.
AB  - A 20-kDa glycoprotein, EPV20, was isolated from bovine milk and characterized.
      The primary structure was determined by cDNA and protein sequencing combined with
      mass spectrometry. EPV20 is a 130-residue polypeptide synthesized with a 19
      residue signal peptide. The function of EPV20 is unknown, but it displays 79%
      sequence similarity to a putative protein deduced from a human testis cDNA
      sequence designated HE1 (human epididymis clone 1) (Kirchhoff, C., 1992.
      EMBL/GeneBank/DDBJ Databases, accession number X67698). Northern blot analysis
      showed the bovine EPV20 to be expressed in kidney, spleen, liver and mammary
      gland, but remarkably not in bovine testis. The six Cys residues of EPV20 were
      found to be disulfide-linked in a 1-6, 2-3 and 4 5 pattern. This disulfide
      arrangement has been observed in other proteins, e.g. in human prostatic acid
      phosphatase, but the spacing between the cystines differs. Therefore, EPV20
      represents a new structure among the large group of proteins containing domains
      with three disulfide bonds.

PMID- 9030771
TI  - Cloning, sequencing and developmental expression of phosphofructokinase from
      Dictyostelium discoideum.
AB  - Phosphofructokinase (PFK) from Dictyostelium discoideum is a non-allosteric
      enzyme that lacks any of the characteristic regulatory mechanisms of PFK from
      other cells. We have determined the DNA sequence and analyzed the amino acid
      sequence of D. discoideum PFK, as an initial step toward understanding the
      peculiar properties of this enzyme. Three overlapping fragments, two of cDNA and
      one of genomic DNA, were isolated, which together could encode the complete
      sequence of D. discoideum PFK. The constructed full-length cDNA coded for a
      protein of 834 amino acids, with a calculated molecular mass of 92.4 kDa, which
      was similar to other eukaryotic and prokaryotic PFK. Alignments of the amino acid
      sequence with other isozymes revealed that many of the amino acid residues
      assigned to binding sites of substrates and allosteric effectors are conserved in
      this enzyme, but changes were also found that may contribute to the absence of
      allosteric mechanisms. A phylogenetic tree for the eukaryotic PFK family was
      constructed and showed that the N-terminal domain clustered with those of yeast
      subunits, whereas the C-terminal domain was more related to PFK from metazoa.
      Southern blotting indicated that D. discoideum PFK is encoded by a single gene.
      The enzyme is present throughout the life cycle of D. discoideum, with a gradual
      decrease of its expression during development.

PMID- 9030772
TI  - Expression and intracellular localization of catechol O-methyltransferase in
      transfected mammalian cells.
AB  - The intracellular localization of soluble and membrane-bound isoforms of rat and
      human catechol O-methyltransferase (COMT) was studied by expressing the
      recombinant COMT proteins either separately or together in mammalian cell lines
      (HeLa and COS-7 cells) and in rat primary neurons. The distribution of soluble
      and membrane-bound COMT enzyme was visualized by immunocytochemistry. For
      comparison, the localization of native COMT was studied in rat C6 glioma cells by
      immunoelectron microscopy. Staining of cells expressing membrane-bound COMT with
      a COMT-specific antiserum revealed an immunofluorescence signal in intracellular
      reticular structures and in the nuclear membrane. Double-staining of the cells
      with antisera against proteins specific for the rough endoplasmic reticulum
      indicated that they colocalized with membrane-bound COMT, suggesting that it
      resided in the endoplasmic reticulum. Notably, no COMT-specific fluorescence of
      plasma membranes was detected. The signal in the endoplasmic reticulum was also
      evident in the cells expressing both recombinant COMT forms. Intracellular native
      COMT reaction was detected by immunoelectron microscopy in rat C6 glioma cells
      and an intense cytoplasmic signal was seen in the primary neurons infected with
      the recombinant Semliki Forest virus. The cells expressing recombinant soluble
      COMT revealed intense nuclear staining together with diffuse cytoplasmic
      immunoreactivity, suggesting that a part of soluble COMT is transported to
      nuclei. Western blotting from rat liver and brain revealed soluble COMT in the
      nuclei. Enzyme activity measurements from liver cytoplasmic and nuclear fractions
      suggested that about 5% of the soluble COMT resided in nuclei. The intracellular
      localization of both COMT forms implies that COMT acts in the cytoplasm and
      possibly also in the nuclear compartment, and that the physiological substrates
      of COMT enzymes may have to be internalized before their methylation by COMT.

PMID- 9030773
TI  - Muscle fibre stress in response to exercise: synthesis, accumulation and isoform
      transitions of 70-kDa heat-shock proteins.
AB  - Heat-shock or stress proteins (HSPs) are considered to play an essential role in
      protecting cells from stress and preparing them to survive new environmental
      challenges. This study investigates the induction kinetics of synthesis and
      accumulation of 70-kDa stress proteins in the soleus and extensor digitorum
      longus (EDL) muscles of the rat following exercise, as well as the isoform
      transitions that take place during the post-exercise period. Relative synthesis
      rates (referred to constitutively expressed stress protein HSP73) of the 70-kDa
      heat-shock proteins were greatly enhanced after a single bout of exercise in both
      muscles. They peaked early in the post-exercise period and returned to resting
      levels after approximately 5-6 h. The levels of the inducible stress protein
      HSP72 in the EDL rose only transiently following exercise, while its accumulation
      in the soleus was more continuous and stable. The amount of HSP73 increased only
      transiently in both muscle types after exercise. The constitutive expression of
      the stress protein HSP72 in the soleus muscle was much higher than in the EDL and
      other tissues, while that of HSP73 was relatively constant among tissues. Rat
      skeletal muscle HSP72 and HSP73 were made up of at least three isoforms of the
      same molecular mass and very close isoelectric points, although only one
      radiolabelled isoform was detected. The relative proportion of the most abundant
      isoforms of HSP72, isoforms 1 and 2, as well as their ratio (isoform 2/isoform
      1), increased during the post-exercise period. Since isoform 2 of HSP72 partially
      disappeared after incubating soleus muscle extracts of exercised rats with
      alkaline phosphatase, these data indicate that phosphorylation of HSP72 is an
      early event in the stress response of skeletal muscle to exercise stress.

PMID- 9030774
TI  - Properties of truncated forms of the elongation factor 1alpha from the archaeon
      Sulfolobus solfataricus.
AB  - Two truncated forms of the Sulfolobus solfataricus elongation factor 1alpha (SsEF
      1alpha), corresponding to the putative domains G+M, Ss(GM)EF-1alpha, and G,
      Ss(G)EF-1alpha, have been constructed by gene engineering, produced in
      Escherichia coli and purified. Neither truncated form was able to sustain
      poly(Phe) synthesis but they were able to bind guanine nucleotides with an
      affinity much higher with respect to that of the intact factor. However, the
      difference in the affinity for GDP and GTP became progressively reduced with the
      extent of the truncation. The values of kcat and Km for GTP of the intrinsic
      GTPase of SsEF-1alpha triggered by 3.6 M NaCl were not affected by the deletions.
      In contrast, both Ss(GM)EF-1alpha and Ss(G)EF-1alpha were less thermostable than
      the intact factor; the region of the factor most responsible for the loss of
      resistance against heat inactivation was the C-terminal domain. On the other hand
      the domain M was the regulator of the thermophilicity of SsEF-1alpha since only
      Ss(G)EF-1alpha showed a reduced thermophilicity. Remarkably, both Ss(GM)EF-1alpha
      and Ss(G)EF-1alpha were able to exchange [3H]GDP for GTP at a very high rate so
      that they were no more sensitive to the stimulatory effect of SsEF-1beta, which
      is the nucleotide exchange factor of SsEF-1alpha.

PMID- 9030775
TI  - Assignment of the ligand geometry and redox potentials of the trihaem
      ferricytochrome c3 from Desulfuromonas acetoxidans.
AB  - Cytochrome c551.5 is a trihaem cytochrome of the cytochrome c3 family isolated
      from Desulfuromonas acetoxidans. Although several X-ray structures are available
      for tetrahaem cytochromes of this family, there is no X-ray structure for trihaem
      cytochromes. Cytochrome C551.5 was studied in the oxidized form by means of two
      dimensional NMR. The pattern of observed interhaem NOESY connectivities is in
      agreement with the haem core structure previously determined by NMR for the
      reduced protein [Coutinho, I. B., Turner, D. L., Liu, M. Y., LeGall, J. & Xavier,
      A. V. (1996) J. Biol. Inorg. Chem. 1, 305-311]. The similarities found between
      the haem core structure and the amino acid sequence of cytochrome c551.5 and
      those of tetrahaem cytochromes c3 allows each of the haems to be specifically
      assigned in the polypeptide sequence, and the attribution of the midpoint redox
      potentials to the individual haems. This also allows individual redox potentials
      to be assigned to each haem in the NMR spectrum. The paramagnetic shifts of the
      13C resonances of the haem substituents were analyzed in terms of pi molecular
      orbitals with perturbed D4h symmetry. The parameters of this analysis have been
      shown to be controlled by the orientation of the axial ligands in several other
      bis-His-coordinated haems and hence the ligand geometry was deduced for
      cytochrome C551.5. The structural analogy between the relative haem plane
      orientations in cytochrome c551.5 and the tetrahaem cytochromes c3 is found to
      extend to the axial ligands with the largest differences being in the vicinity of
      the deleted fourth haem, using the numbering of cytochrome c3 haems.

PMID- 9030776
TI  - Effects of minor and major groove-binding drugs and intercalators on the DNA
      association of minor groove-binding proteins RecA and deoxyribonuclease I
      detected by flow linear dichroism.
AB  - Linear and circular dichroic spectroscopies have been employed to investigate the
      effects of small DNA ligands on the interactions of two proteins which bind to
      the minor groove of DNA, viz. RecA protein from Escherichia coli and
      deoxyribonuclease I (bovine pancreas). Ligands representing three specific non
      covalent binding modes were investigated: 4',6-diamidino-2-phenylindole and
      distamycin A (minor groove binders), methyl green (major groove binder), and
      methylene blue, ethidium bromide and ethidium dimer (intercalators). Linear
      dichroism was demonstrated to be an excellent detector, in real time, of DNA
      double-strand cleavage by deoxyribonuclease I. Ligands bound in all three modes
      interfered with the deoxyribonuclease I digestion of dsDNA, although the level of
      interference varied in a manner which could be related to the ligand binding
      site, the ligand charge appearing to be less important. In particular, the
      retardation of deoxyribonuclease I cleavage by the major groove binder methyl
      green demonstrates that accessibility to the minor groove can be affected by
      occupancy of the opposite groove. Binding of all three types of ligand also had
      marked effects on the interaction of RecA with dsDNA in the presence of non
      hydrolyzable cofactor adenosine 5'-O-3-thiotriphosphate, decreasing the
      association rate to varying extents but with the strongest effects from ligands
      having some minor groove occupancy. Finally, each ligand was displaced from its
      DNA binding site upon completion of RecA association, again demonstrating that
      modification of either groove can affect the properties and behaviour of the
      other. The conclusions are discussed against the background of previous work on
      the use of small DNA ligands to probe DNA-protein interactions.

PMID- 9030777
TI  - Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its
      cleavage by plasmin.
AB  - Vitronectin, found in the extracellular matrix and in circulating blood, has an
      important role in the control of plasminogen activation. It was shown to be the
      major protein substrate in human blood fluid for a protein kinase A (PKA)
      released from platelets upon their physiological stimulation with thrombin. Since
      vitronectin was shown to have only one PKA phosphorylation site, but to contain 2
      3 mol covalently bound phosphate, it was reasonable to assume that other protein
      kinases might phosphorylate vitronectin at other sites in the protein. We have
      reported earlier that human serum contains at least three protein kinases, one of
      which was found to be cAMP independent and to phosphorylate a repertoire of
      plasma proteins that was very similar to that obtained upon phosphorylation of
      human plasma with protein kinase C (PKC). Since there are now several examples of
      proteins with extracellular functions that are phosphorylated by PKC, we
      undertook to study the phosphorylation of vitronectin by PKC. Here, we show that
      vitronectin is a substrate for PKC, and characterize the kinetic parameters of
      this phosphorylation (Km approximately tenfold lower than the concentration of
      vitronectin in blood), indicating that, from the biochemical point of view, this
      phosphorylation can occur at the locus of a hemostatic event. We also identify
      Ser362 as the major PKC phosphorylation site in vitronectin, and confirm this
      localization by means of synthetic peptides derived from the cluster of basic
      amino acids in vitronectin surrounding Ser362. We show that the PKC
      phosphorylation at Ser362 alters the functional properties of vitronectin,
      attenuating its cleavage by plasmin at Arg361-Ser362. This phosphorylation has
      the potential to regulate plasmin production from plasminogen by a feedback
      mechanism involving the above-mentioned plasmin cleavage, a loosening of the
      vitronectin grip on inhibitor 1 of plasminogen activators, and a subsequent
      latency of this regulatory inhibitor.

PMID- 9030778
TI  - The neuronal cell-adhesion molecule axonin-1 is specifically released by an
      endogenous glycosylphosphatidylinositol-specific phospholipase.
AB  - Axonin-1, a member of the immunoglobulin/fibronectin type-III family of cell
      adhesion molecules, occurs both as a glycosylphosphatidylinositol
      (glycosylPtdIns)-anchored membrane-bound and a soluble form. In vivo observations
      show that the major part of axonin-1 is found in the soluble fraction and that
      soluble axonin-1 perturbs neurite fasciculation and pathfinding in the developing
      chicken embryo. This has prompted further investigations into the mechanism of
      the axonin-1 release. We demonstrate here that axonin-1 released from dorsal root
      ganglion neurons contains ethanolamine and inositol, components of the
      glycosylPtdIns anchor. Secreted axonin-1 does not exhibit the cross-reacting
      determinant epitope, an indication that the cleavage of the anchor is not
      mediated by a phosphatidylinositol-specific phospholipase C. Treatment of dorsal
      root ganglion neurons with 1,10-phenanthroline, an inhibitor of glycosylPtdIns
      specific phospholipase D, reduces the release of axonin-1 by 56%. Moreover,
      glycosylPtdIns-specific phospholipase D activity was detected in dorsal root
      ganglion neurons and brain. These results suggest that axonin-1 is released from
      the membrane by an endogenously expressed glycosylPtdIns-specific phospholipase D
      in vivo. With domain-swaping experiments between axonin-1 and its non-released
      relative F11, deletion mutants and monoclonal antibodies, we demonstrate that the
      fourth fibronectin type-III-like domain of axonin-1 is required for the
      generation of the soluble form of axonin-1.

PMID- 9030779
TI  - Functional characterization of the N-glycosylation sites of human acid
      sphingomyelinase by site-directed mutagenesis.
AB  - Most soluble lysosomal enzymes require a mannose-6-phosphate recognition marker
      present on asparagine-linked oligosaccharides for proper targeting to lysosomes.
      We have determined the influence of the six potential N-linked oligosaccharide
      chains of human acid sphingomyelinase (ASM) on catalytic activity, targeting, and
      processing of the enzyme. Each N-glycosylation site was modified by site-directed
      mutagenesis and subsequently expressed in COS-1 cells. Evidence is presented that
      five of these sites are used. Elimination of the four N-terminal glycosylation
      sites does not disturb lysosomal targeting, processing, or enzymatic activity.
      However, removal of the two C-terminal N-glycosylation sites inhibits the
      formation of mature enzyme. Absence of glycosylation site five resulted in rapid
      cleavage of the primary translation product to an enzymatically inactive protein
      which accumulated inside the endoplasmic reticulum/Golgi, whereas deletion of
      glycosylation site six led to the formation of an inactive ASM precursor, also
      retained inside the endoplasmic reticulum/Golgi. Our results also provide
      evidence that the site of early proteolytic cleavage of newly synthesized ASM
      must be located between the second and third glycosylation sites.

PMID- 9030780
TI  - Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of
      human cdk2 complexed with roscovitine.
AB  - Cyclin-dependent kinases (cdk) control the cell division cycle (cdc). These
      kinases and their regulators are frequently deregulated in human tumours. A
      potent inhibitor of cdks, roscovitine [2-(1-ethyl-2-hydroxyethylamino)-6
      benzylamino-9-isopropylpurin e], was identified by screening a series of C2,N6,N9
      substituted adenines on purified cdc2/cyclin B. Roscovitine displays high
      efficiency and high selectivity (Meijer, L., Borgne, A., Mulner, O., Chong, J. P.
      J., Blow, J. J., Inagaki, N., Inagaki, M., Delcros, J.-G. & Moulinoux, J.-P.
      (1997) Eur. J. Biochem. 243, 527-536). It behaves as a competitive inhibitor for
      ATP binding to cdc2. We determined the crystal structure of a complex between
      cdk2 and roscovitine at 0.24-nm (2.4 A) resolution and refined to an Rfactor of
      0.18. The purine portion of the inhibitor binds to the adenine binding pocket of
      cdk2. The position of the benzyl ring group of the inhibitor enables the
      inhibitor to make contacts with the enzyme not observed in the ATP-complex
      structure. Analysis of the position of this benzyl ring explains the specificity
      of roscovitine in inhibiting cdk2. The structure also reveals that the (R)
      stereoisomer of roscovitine is bound to cdk2. The (R)-isomer is about twice as
      potent in inhibiting cdc2/cyclin B than the (S)-isomer. Results from
      structure/activity studies and from analysis of the cdk2/roscovitine complex
      crystal structure should allow the design of even more potent cdk inhibitors.

PMID- 9030782
TI  - Can the outcome of coronary bypass grafting be predicted reliably?
AB  - OBJECTIVE: To test prospectively the unsubstantiated claim that patient-specific
      predictions of time-related outcome after coronary artery bypass grafting (CABG)
      from multivariable parametric equations are reliable for medical decision making
      and for intra- and interdepartmental quality control in surgical training and
      practice. METHODS: 3720 survival curves were generated prospectively for all
      primary, isolated CABG patients operated upon at the Katholieke Universiteit (KU)
      Leuven between July, 1987 and January, 1992 using the published AHA/ACC
      guidelines multivariable equation derived from prior KU Leuven experience. The
      average of these curves (risk-adjusted predicted survival) was compared to the
      Kaplan-Meier (actual) estimates, overall and for patient subsets. Variables
      associated with systematic deviation of actual from predicted number of deaths
      were sought by multivariable residual risk analysis. RESULTS: Actual overall
      survival was less good than predicted (P = 0.03) and the excess risk was
      distributed uniformly across time. The excess risk was not attributable to
      substantial changes in prevalence of known risk factors. It was attributable
      largely to a small subset of patients (n = 292) with low-prevalence, but
      important risk factors not accounted for by the equation (P = 0.7, for difference
      in survival among the remaining 3428 patients). CONCLUSIONS: Within the confines
      of a single institution, patient-specific predictions of outcome after CABG can
      be made reliably in most patients using multivariable equations developed from a
      heterogeneous experience, despite changes in prevalence of risk factors. New
      subsets of high-risk patients, failure or inability to account for important rare
      risk factors or for institutional changes, may lead to systematic errors of
      prediction. Under these limitations it is an excellent tool for medical decision
      making and audit of surgical training and practice.

PMID- 9030783
TI  - Routine registration of deviations from the norm in cardiac surgery: a potent
      clinical research tool and quality assurance measure.
AB  - The surveillance and monitoring of deviations from normality is an often used
      quality assurance weapon in private industry. In cardiac surgery, complications
      have often been monitored and reported, but mostly one at a time and in
      conjunction with a scientific study. METHODS: Using the clinic's data network
      including operating theatre, intensive care unit and ward, deviations from a
      normal postoperative course are registered by the patient's nurses. The
      deviations are registered by answering questions on all organ systems in front of
      a PC. Suitable definitions are available to the nurse. When the patient is
      discharged, the surgeon in charge will review the deviations noted and make a
      formal diagnosis on the patient's chart if appropriate. RESULTS: The data system
      has now been in use for 6 months. It was easily adopted by the nurses. The
      doctor's work is facilitated as relevant data are available to him when
      discharging the patient and making the discharge note. 58% of the patients have
      some kind of deviation from the norm, most commonly in the cardiovascular system
      (30% of the patients), respiratory system (22%), and surgically complicated
      postoperative course (17%). During the first months of registration it became
      apparent that too many patients had postoperative thrombophlebitis. By changing
      routines, the incidence of thrombophlebitis decreased from 5 to < 1%. CONCLUSION:
      Only about 40% of our patients go through a cardiac operation with a totally
      normal postoperative course. The registration system has turned out to be easily
      handled by our nurses and able to detect complications not immediately noticed in
      everyday clinical practice. A registry of this kind is highly dependent on its
      definitions and on the general 'norm' prevailing. Findings from such registries
      cannot therefore be immediately compared with those of other institutions. The
      research potentials of the registry as well as its role in quality assurance seem
      large.

PMID- 9030781
TI  - Biochemical and cellular effects of roscovitine, a potent and selective inhibitor
      of the cyclin-dependent kinases cdc2, cdk2 and cdk5.
AB  - Cyclin-dependent kinases (cdk) play an essential role in the intracellular
      control of the cell division cycle (cdc). These kinases and their regulators are
      frequently deregulated in human tumours. Enzymatic screening has recently led to
      the discovery of specific inhibitors of cyclin-dependent kinases, such as
      butyrolactone I, flavopiridol and the purine olomoucine. Among a series of C2,
      N6, N9-substituted adenines tested on purified cdc2/cyclin B, 2-(1-ethyl-2
      hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine) displays high
      efficiency and high selectivity towards some cyclin-dependent kinases. The kinase
      specificity of roscovitine was investigated with 25 highly purified kinases
      (including protein kinase A, G and C isoforms, myosin light-chain kinase, casein
      kinase 2, insulin receptor tyrosine kinase, c-src, v-abl). Most kinases are not
      significantly inhibited by roscovitine. cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin
      E and cdk5/p35 only are substantially inhibited (IC50 values of 0.65, 0.7, 0.7
      and 0.2 microM, respectively). cdk4/cyclin D1 and cdk6/cyclin D2 are very poorly
      inhibited by roscovitine (IC50 > 100 microM). Extracellular regulated kinases
      erk1 and erk2 are inhibited with an IC50 of 34 microM and 14 microM,
      respectively. Roscovitine reversibly arrests starfish oocytes and sea urchin
      embryos in late prophase. Roscovitine inhibits in vitro M-phase-promoting factor
      activity and in vitro DNA synthesis in Xenopus egg extracts. It blocks
      progesterone-induced oocyte maturation of Xenopus oocytes and in vivo
      phosphorylation of the elongation factor eEF-1. Roscovitine inhibits the
      proliferation of mammalian cell lines with an average IC50 of 16 microM. In the
      presence of roscovitine L1210 cells arrest in G1 and accumulate in G2. In vivo
      phosphorylation of vimentin on Ser55 by cdc2/cyclin B is inhibited by
      roscovitine. Through its unique selectivity for some cyclin-dependent kinases,
      roscovitine provides a useful antimitotic reagent for cell cycle studies and may
      prove interesting to control cells with deregulated cdc2, cdk2 or cdk5 kinase
      activities.

PMID- 9030784
TI  - Lung metastases of renal cell carcinoma: results of surgical resection.
AB  - OBJECTIVE: The research was designed to evaluate the results of surgical
      resection of renal lung metastases. METHODS: Between 1960 and 1994, 50
      consecutive patients underwent resection for pulmonary metastases from renal cell
      carcinoma. Mean age was 59 years (range: 40-78 years). Mean time between
      nephrectomy and pulmonary resection was 3 years (range: 0-18 years). Nineteen
      patients had solitary metastase, 13 multiple unilateral, and 18 bilateral. Wedge
      excision was performed in 28 patients, segmentectomy in 3, lobectomy in 17,
      sleeve lobectomy in 1, pneumonectomy in 5 and biopsy in 3. Twelve patients had
      repeat resection for recurrent metastases. RESULTS: The resection was complete in
      45 patients. Three patients also had a complete resection of limited extra
      pulmonary disease. There was one postoperative death and 3 complications. Mean
      follow-up was 42 months without loss of follow-up. The cause of death was always
      metastatic recurrent disease. Five-year survival in complete resection was 44%.
      Only one long survivor was observed in the case of incomplete resection in a
      patient who had a complete response after adjuvant immunotherapy. Five-year
      survival for the 12 patients with repeat resections was similar to the overall
      survival rate (42%). CONCLUSIONS: Resection of renal lung metastases is a safe
      and effective treatment. No factor influenced the 5-year survival in this series
      except the complete resection. Extra-pulmonary metastases does not contra
      indicate pulmonary resection. In selected patients, repeat resection for
      recurrent disease is warranted.

PMID- 9030785
TI  - Efficacy and safety of videothoracoscopic lung biopsy in the diagnosis of
      interstitial lung disease.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy and safety of
      videothoracoscopic lung biopsy (VTLB) in the diagnosis of infiltrative lung
      disease (ILD) and compare the results of VTLB with the results previously
      obtained in patients with open lung biopsy at the same institution. METHODS:
      Forty-one patients undergoing VTLB between May 1991 and December 1994 were
      retrospectively studied and compared with 25 patients who have undergone OLB
      during the period from January 1987 to April 1991. The two groups were comparable
      with respect to age, sex, and severity of lung disease. RESULTS: Three of 41
      patients (7%) who underwent VTLB with minithoracotomy. There was no significant
      difference between the group of VTLB (38 patients) and the group OLB (25
      patients) with regard to, the number of biopsies (VTLB 1.8 +/- 0.4 versus OLB 2
      +/- 0.6), or diagnostic yield (VTLB 37/38 versus OLB 25/25). In contrast,
      patients who underwent VTLB demonstrated a significant reduction of the operative
      time (VTLB 45.3 +/- 12.2 min), length of chest tube drainage (3.55 +/- 1.2 days),
      hospital stay (5.5 +/- 1.3 days), and analgesia (buprenorphine 0.85 +/- 0.44 mg;
      paracetamol 5.9 +/- 2.5 g) compared to patients who underwent OLB (55.6 +/- 11.2
      min, 5.2 +/- 1.5 days; 7.1 +/- 2.3 days; buprenorphine 1.17 +/- 0.5 mg,
      paracetamol 8.9 +/- 2.3 g). Morbidity and mortality were similar in the two
      groups (morbidity VTLB 10.5%, OLB 12%; mortality VTLB 5.2%, OLB 8%). Regardless
      of the biopsy technique, the most serious complications and deaths occurred with
      the same frequency in those patients with a severe underlying disease.
      CONCLUSIONS: VTLB is a valid alternative to OLB in most cases. Along with a
      comparable efficacy, VTLB has several advantages that should make it the method
      of choice for patients with only minimally impaired respiratory function. In
      contrast, the role and advantages of VTLB compared to OLB in patients with severe
      lung disease, require further investigation.

PMID- 9030786
TI  - Does a thoracoscopic approach for surgical treatment of spontaneous pneumothorax
      represent progress?
AB  - OBJECTIVE: Surgical management is indicated in recurrent forms of pneumothorax
      and for failure of tube drainage. We have for several years performed pleurodesis
      and apical blebs stapling by axillary thoracotomy. Thoracoscopy has been a well
      established procedure for 70 years and recently further developed as the result
      of current technological progress. For 10 years thoracoscopy has been developed
      as an alternative to thoracotomy in several indications. Spontaneous pneumothorax
      is ideally suitable for thoracoscopic management. The aim of this retrospective
      study is to evaluate this new approach. METHODS: We compare our results of
      axillary thoracotomy management of spontaneous pneumothorax in 237 patients
      (group 1) with those of thoracoscopic management in 101 patients (group 2). Sex
      distribution, average age, indications and stapling of apical blebs were
      comparable in both groups. RESULTS: Etiologies were comparable in both groups.
      The average operation time was 71 min in group 1 and 57 min in group 2. The
      average duration of chest tube placement was 8 days in group 1 and 6.5 days in
      group 2. The mean hospital stay was 14 days in group 1 and 9.5 days in group 2.
      The overall morbidity was 16 and 11% in groups 1 and 2, respectively. The most
      frequent complication was early or late failure of pleurodesis which required
      second drainage or a subsequent operation. Late failure occurred more frequently
      after thoracoscopy (3 vs. 0.4%) but there was no statistically significant
      difference between the two groups. CONCLUSIONS: Thoracoscopic management of
      spontaneous pneumothorax is a safe procedure. Moreover, it offers the benefits of
      a shorter hospital stay and less postoperative pain.

PMID- 9030787
TI  - Surgical therapy of esophageal carcinoma: the influence of surgical approach and
      esophageal resection on cardiopulmonary function.
AB  - OBJECTIVE: The effects of the different surgical approaches (transhiatal
      esophagectomy and right-sided transthoracic esophagectomy) on perioperative
      cardiopulmonary function in the surgical treatment of esophageal carcinoma are
      discussed controversially and have not yet been evaluated. METHODS: In a
      prospective randomized study including 32 patients, we investigated the effects
      of the surgical approach (blunt dissection (n = 16) versus transthoracic en-bloc
      resection (EB) (n = 16)) in the treatment of esophagus carcinoma on perioperative
      cardiopulmonary function. The following parameters were measured in all patients:
      cardiac index (CI), mean arterial pressure (MAP), central venous pressure (CVP),
      mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP),
      intrapulmonary shunt (QS/QT), arterio-alveolar (aaDO2), arterio-venous oxygen
      pressure difference (avDO2), and blood gas analyses. Time of measurement were:
      after induction of anesthesia, beginning and end of esophagus resection, end of
      surgery, 1 h postoperatively, and then every 12 h until the third postoperative
      day. RESULTS: Compared to blunt dissection, en-bloc esophagectomy was found to be
      associated with a transient deterioration of pulmonary function during one-lung
      ventilation in the left-lateral position, which could already be compensated for
      during the intervention. No other significant differences in cardiopulmonary
      effects were seen between the two surgical techniques. The incidence of
      postoperative complications was identical in both groups. CONCLUSIONS: The
      results of our study show that en-bloc resection is only associated with an
      increased intraoperative pulmonary strain that is completely compensated during
      the operation and that there is no difference in cardiopulmonary functions
      between the two techniques in the postoperative course.

PMID- 9030788
TI  - Management of non resectable malignant esophageal stricture and fistula.
AB  - OBJECTIVE: The palliation of dysphagia caused by esophageal carcinoma and other
      inoperable tumours obstructing the esophagus presents a challenge for the
      thoracic surgeon, in particularly when associated with fistula (F). In a
      prospective study over the last 5 years, we have evaluated the effectiveness of
      different approaches and types of prostheses to solve the above problem. METHOD:
      Thirty three patients (mean age: 63.5 years, range 42-76, M/F:24/9) with
      inoperable tumours obstructing the esophagus underwent intubation and/or
      palliative surgery according to the following protocol: (1) Preoperative
      esophagography; (2) endoscopy and biopsy; (3) dilatation and insertion of
      prosthesis usually under general anaesthesia; and (4) re-evaluation the following
      day, in 30 days and as required thereafter. Prosthesis used were: Atkinson 3,
      Wilson-Cook (plain) 12, Wilson-Cook (cuffed) 4, Strecker (metallic self
      expandable) 13. The patients were divided in three groups according to the
      extension of the disease: group A (n = 19) plain malignant strictures, group B (n
      = 5) strictures with respiratory Fs, group C (n = 9) strictures with mediastinal
      or pleural Fs. RESULTS: All patients of group A had successful palliation
      irrespectively of prosthesis used and site of obstruction. One patient required
      two stents. There was no death and 50% survival at 6 months was 70%. In group B,
      a cuffed prosthesis successfully closed two bronchoesophageal Fs, while three
      patients underwent retrosternal bypass surgery. There was one death on the 26th
      postoperative day. In group C, one Strecker, two plain Wilson-Cook and two cuffed
      Wilson-Cook stents, although initially succeeded, in due course, failed to block
      the Fs in five patients who subsequently underwent bypass surgery with one death.
      With four patients both leak and dysphagia were significantly improved with the
      use of self-expandable stents therefore, not requiring surgery. Overall, there
      were two deaths but no failure in palliating dysphagia. Longer survival was 20
      months. Patients with fistulae had poorer prognosis as compared to those
      suffering from plain malignant stricture (P = 0.01). CONCLUSIONS: Plain malignant
      inoperable oesophageal strictures can be successfully palliated with intubation.
      Complicated with fistula strictures, however, are difficult to manage and have a
      poor prognosis. Due to the fact that bypass surgery is associated with an
      increased mortality, it should be kept for those with late stent failures and
      fistula recurrences.

PMID- 9030789
TI  - Long-term results of surgery for active infective endocarditis.
AB  - OBJECTIVE: This paper was undertaken to determine the long-term outcome of active
      infective endocarditis treated with antibiotic and radical excision of infected
      tissues by surgery. METHODS: From October 1978 to August 1994, 122 consecutive
      patients were operated on during the acute phase of infective endocarditis. There
      were 85 men and 37 women whose mean age was 50 years, ranging from 20 to 79.
      Surgery was needed because of one or more of the following complications:
      cardiogenic/septic shock in 19 patients, congestive heart failure in 68,
      persistent sepsis in 64, peripheral embolization in 20, and cerebral embolization
      in 10. The offending microorganism was identified in 110 patients, staphylococci
      were the most common ones. Seventy-six patients had native valve endocarditis and
      46 had prosthetic valve endocarditis. Simple valve replacement or repair was
      performed in 60 patients and radical resection of the valve and surrounding
      tissues with reconstruction of the heart with either fresh autologous pericardium
      or glutaraldehyde-fixed bovine pericardium was performed in 62 with paravalvular
      abscess. Pulmonary autograft and aortic homograft were used in only three
      patients, the remaining patients had either bioprostheses or mechanical heart
      valves if valve repair was not feasible. RESULTS: There were nine deaths, for an
      operative mortality of 7.4%. Logistic regression analysis identified preoperative
      shock and renal failure as predictors of operative mortality. Operative survivors
      were followed up from 4 to 173 months, mean of 56.4. The actuarial survival at 10
      years was 61 +/- 6%. Logistic regression analysis identified preoperative New
      York Heart Association functional class IV and perioperative renal failure as
      predictors of late mortality. Eight patients developed recurrent endocarditis 10
      102 months postoperatively. The freedom from recurrent endocarditis at 10 years
      was 79 +/- 9%. All patients who developed this late complication had paravalvular
      abscess at the time of original operation. CONCLUSIONS: These data suggest that
      surgery for active infective endocarditis yield a high probability of eradicating
      the infection with relatively low operative mortality and good long-term results.

PMID- 9030790
TI  - Emergency surgery for acute infective aortic valve endocarditis: performance of
      cryopreserved homografts and mode of failure.
AB  - OBJECTIVE: To describe our experience in the surgical treatment of infective,
      native and prosthetic aortic valve endocarditis, using cryopreserved homograft
      valves. METHODS: Between January 1988 and September 1995, cryopreserved
      homografts were implanted in 49 patients (mean age 47 +/- 15 years; range 19-79)
      with acute infective endocarditis of the native (21/49; 43%) or the prosthetic
      (28/49; 57%) aortic valve. Aortic root abscesses were found in 39/49 (80%)
      patients, ventriculo-aortic disconnection in 27/49 (55%). An intracardiac
      fistula, originating from the left ventricular outflow tract was found in 25/49
      (51%) patients. Indications for emergency surgery were congestive heart failure
      due to severe aortic valve regurgitation in 44/49 (90%) and systemic emboli in
      5/49 (10%) patients. Preoperatively, 23/49 (47%) patients were in New York Heart
      Association (NYHA) class IV, and 5/49 (10%) were in acute circulatory failure.
      Mean left ventricular ejection fraction was 53 +/- 10% (25-65). Streptococci
      (27%) and staphylococci (27%) were the most important microorganisms found. The
      homograft was implanted as a scalloped freehand valve (34/49; 70%), as an intra
      aortic inclusion cylinder (4/49; 6%) or as a free-standing root replacement
      (12/49; 24%). Combined procedures were necessary in 11/49 (22.5%) patients.
      RESULTS: Hospital mortality was 8.2% (4/49): 2/49 (4.1%) patients died from
      endocarditis-related sepsis, one (2%) from low cardiac output and one (2%) from a
      cerebrovascular accident. After a mean interval of 21 +/- 15 months (2-48), 9/45
      (20%) patients had to be reoperated, all reoperations except one being homograft
      related. After a mean follow-up of 35 +/- 22 months (2-90), 4/44 (9%) patients
      had their homograft replaced by a mechanical prosthesis. After 5 years, actuarial
      freedom from late death was 97 +/- 3%; from late reoperation 69 +/- 9%; from late
      endocarditis 85 +/- 8%; and from late homograft degeneration 87 +/- 6%. Explanted
      homografts were acellular and non-vital, containing bacteria and/or leucocytes. B
      lymphocytes were found in all and in one, T-cell lymphocytes were present.
      CONCLUSION: Emergency aortic valve replacement with cryopreserved homografts for
      acute native or prosthetic aortic valve endocarditis has a low operative
      mortality. The late incidence of recurrent endocarditis or homograft failure up
      to 7 years is acceptable. Cryopreserved homografts are non-viable. The presence
      of T-cell lymphocytes in explanted homografts indicates that rejection may be
      possible.

PMID- 9030791
TI  - Risk factors for early degeneration of allografts in pulmonary circulation.
AB  - OBJECTIVE: The aim of this study was to define risk factors for early
      degeneration of allografts in pulmonary circulation and to recommend some
      guidelines to minimize them. METHODS: Between January 1988 and March 1995, 202
      patients with various types of congenital heart disease received cryopreserved
      allograft conduits for reconstruction of their right ventricular outflow tract.
      We report on 63 patients receiving allografts ranging from 9-24 mm size within
      the first 2 years of life. RESULTS: Survivors have been followed for 4-67 months.
      Survival at 5 years, including hospital mortality, was 66%. Two patients died at
      reoperation. Of the patients 19.6% (9/46) had early structural deterioration (SD)
      of their vascular allografts at a mean of 15.2 months after implantation. Seven
      of these have already been reoperated with allograft exchange. Freedom of
      reoperation was 66% at 5 years. Infants showed 48% freedom of reoperation at 5
      years compared to 90% in the 1-2 years age group, while freedom of SD was 59% in
      infants at 48 months compared to 87% in the 1-2 years age group. Of allografts
      with SD in the infant group 66% had an allograft size of < 14 mm. In aortic
      allografts freedom of SD was 62% compared to 93% in pulmonary allografts. Freedom
      of allograft wall calcification was 46% at 18 months in all patients. In the
      statistical analysis, only infant age (P = 0.03) and aortic allograft (P = 0.02)
      were shown to be significant risk factors for early SD. CONCLUSION: The use of
      pulmonary allografts, avoidance of relatively short and small conduits of < 14 mm
      in diameter, might improve the durability of allografts in infants and small
      children.

PMID- 9030792
TI  - Role of atrial ischaemia in development of atrial fibrillation following coronary
      artery bypass surgery.
AB  - OBJECTIVE: Atrial fibrillation (AF) is a common complication after coronary
      artery bypass grafting (CABG) operations, occurring in 5 to 40% of cases. A
      number of studies have implicated atrial ischaemia in the genesis of this
      arrhythmia. The aim of this study was to examine the relationship between atrial
      coronary anatomy and the incidence of post operative atrial fibrillation. METHOD:
      To investigate a possible anatomical explanation to the onset of AF after CABG,
      25 patients with documented AF after CABG were matched and compared to 25
      patients which remained in sinus rhythm (SR). All coronary angiograms were
      reported blindly by a cardiac radiologist with reference to the blood supply of
      the sino-atrial (SA) node and atrio-ventricular (AV) node before and after
      surgery. RESULTS: Univariate analysis of risk factors did not identify any
      significant difference (Fisher exact test, P > 0.05) between the two groups in
      age, gender, left ventricular function, ischaemic time, number of vessels
      diseased or grafted, renal dysfunction and withdrawal of beta-blockade. However,
      significant disease in the SA nodal artery was present in 2 patients of the SR
      group when compared to 9 in the AF group. Significant disease of AV nodal artery
      was present in only 4 patients of the SR group when compared to 18 in the AF
      group. Comparison between the two groups showed a significantly increased
      incidence of SA or AV nodal artery disease in the AF group, (SA: P = 0.018, AV: P
      = 0.0001). Mean hospital stay was 8.1 days for the SR group and 9.1 days in the
      AF group (P = 0.175). CONCLUSION: Obstructive disease in the SA nodal and AV
      nodal arteries is more common in patients developing atrial fibrillation
      following coronary artery bypass surgery than those who remain in sinus rhythm.
      If the incidence of AF could be predicted by the anatomical distribution of
      arterial disease then targeting prophylaxis to this group may be possible.

PMID- 9030793
TI  - Spontaneous cardioversion and mitral valve repair: a role for surgical
      cardioversion (Cox-maze)?
AB  - OBJECTIVE: The objectives of this study are to describe: (1) The incidence of
      change in pre-operative rhythm (cardioversion) with mitral valve repair early and
      at 1 year's review after surgery (late). (2) The characteristics of those
      patients who remain in atrial fibrillation (AF) or sinus rhythm (SR) at late
      follow up. (3) The characteristics of those patients whose rhythm is seen to
      change (cardiovert) from SR to AF, or AF to SR and to remain so at 1 year. In
      this way it is hoped to more clearly define those patients who would benefit from
      the combination of mitral valve repair and surgical cardioversion (Cox-maze
      procedure). METHODS: Retrospective study was made of the case notes of all
      patients undergoing mitral repair at our hospital during the 3 years between
      January 1st, 1991 and December 31st, 1993. Early (hospital discharge) and late (1
      year) post operative e.c.g. rhythm was compared to pre-operative e.c.g. rhythm.
      The study explored the association of cardioversion with pre-operative rhythm,
      patient age, aetiology of mitral valve lesion (mitral regurgitation or stenosis)
      and echo cardiographic estimations of left atrial size and left ventricular
      dimensions. RESULTS: Patients (89) underwent repair with a 30 day mortality of
      2.2% (2 of 89). Of these, 55 were male with an average age of 65 +/- 12 years.
      Regurgitation was the valvular lesion in 93% and 18% were associated with
      coronary artery disease, 48 (55%) were in SR before surgery. Both deaths occurred
      in patients with AF as a pre-operative rhythm. Of the 39 survivors originally in
      AF, only one was of recent onset ( < 6 months). The frequency of an enlarged left
      atrium (> or = 5.0 cm) was significantly greater in those with AF compared to SR
      (P < 0.001). Atrial fibrillation was also associated with increasing age (P =
      0.006) and increasing left ventricular end systolic diameter (LVESD; P = 0.018).
      Spontaneous cardioversion of pre-operative rhythm was common at the time of
      hospital discharge (AF to SR: 46% and SR to AF: 25%). At the 1 year review after
      mitral repair only 8 (21%) of those originally in AF were then in sinus rhythm.
      Eight (17%) of those originally in SR were in AF. A lower left ventricular end
      systolic diameter (LVESD) was associated with spontaneous cardioversion of AF to
      SR by one year (P = 0.005). Similarly, patients originally in SR with a lower
      LVESD continued in SR. Those with a higher value were seen to cardiovert to AF (P
      < 0.05). CONCLUSIONS: Immediately prior to surgery the presence of AF was
      associated with a tendency to larger left atrial size, older age and a greater
      LVESD. Cardioversion was common for both patients in AF (46%) and SR (25%) early
      following conservative mitral surgery. The prevalence of late cardioversion was
      of a similar order in both those originally in AF (21%) and SR (17%). The
      maintenance of, or cardioversion to SR seemed to be characterised only by the
      LVESD. This analysis captures many of the problems of retrospective review. A
      multi-centre, prospective study is proposed to achieve the aim of an accurate
      formula predicting long standing cardioversion with mitral valve surgery.

PMID- 9030794
TI  - Long-term relative survival after primary heart valve replacement.
AB  - OBJECTIVE: Determination of the optimal timing of primary heart valve replacement
      is an important issue. The present paper provides a synopsis over early and late
      survival after primary heart valve replacement, including an evaluation of the
      excess mortality among heart valve replacement patients compared with the general
      population. METHODS: Survival was analyzed in 2365 patients (1568 without and 797
      with concomitant coronary artery bypass grafting (CABG)) who underwent their
      first heart valve replacement. Observed survival was related to that expected
      among persons from the general Swedish population stratified by age, sex, and 5
      year calendar period, to calculate the relative survival and estimate the disease
      specific survival. RESULTS: Early mortality (death within 30 days after surgery)
      was 5.9% after aortic valve replacement, 10.4% after mitral valve replacement and
      10.6% after combined aortic and mitral valve replacement. Relative survival rates
      (excluding early deaths) were 84% 10 years after aortic, 68.5% after mitral and
      80.9% after both aortic and mitral valve replacement. A multivariate model based
      on observed survival rates was produced for each group, using the Cox
      proportional hazards model. Concomitant CABG, advanced New York Heart Association
      (NYHA) class, preoperative atrial fibrillation, pure aortic regurgitation and
      higher age increased the late observed survival after aortic valve replacement.
      NYHA class was the only factor independently related to observed late deaths
      after mitral valve replacement, and mitral insufficiency the only corresponding
      factor after both aortic and mitral valve surgery. CONCLUSION: The use of
      relative survival rates tended to modify the difference between subgroups
      compared with observed survival rates. Relative survival rates reduced the effect
      of concomitant CABG on survival, but enhanced for example the effect of aortic
      regurgitation. In patients > or = 70 years of age and patients submitted to
      aortic or mitral valve replacement with mild or no symptoms, the survival rate
      was similar for many years to that in the Swedish population at large.

PMID- 9030795
TI  - Ross procedure in congenital patients: results and left ventricular function.
AB  - METHODS: From April 1990 to August 1995, 121 patients (median age 42 years)
      underwent aortic valve replacement with allografts (69 patients) or autografts
      (52 patients). In this latter group, 24 Ross procedures have been performed in
      congenital patients since November 1991 (median age 10 years, range five months
      to 27 years): aortic incompetence (n = 17), isolated aortic stenosis (n = 5),
      small stenotic prosthesis (n = 2). Transthoracic echocardiography was obtained
      preoperatively in all patients and serially after surgery with the aim of
      measuring aortic and pulmonary annuli and evaluate gradients and incompetence and
      to study the left ventricular function. Intraoperative transoesophageal
      echocardiography was routinely used. Complete root replacement was performed in
      all patients. RESULTS: One patient died in the early postoperative period (4%).
      There was no late death. All survivors remained in NYHA class I and were free of
      complications and medications. No gradient nor any significant aortic
      incompetence could be demonstrated. In 17 patients with predominant aortic
      incompetence before surgery, the left ventricular function was followed
      prospectively, end-diastolic left ventricular dimensions diminished drastically
      from 2 +/- 3.4 S.D. above normal to -0.63 +/- 2.4 S.D. at one week
      postoperatively (day 10) to reach a normal value one to three months after
      surgery. Left ventricular mass remained abnormal at day 10 (from 4.7 +/- 3.3 S.D.
      to 5.3 +/- 3.8 S.D.) and diminished more progressively to reach a normal value
      (0.14 +/- 1.4 S.D.) at three months. This resulted in a significant decrease of
      end-systolic wall stress (-3.6 +/- 2.1 S.D.) and in a hyperdynamic function in
      the immediate postoperative days except in two patients. These two patients were
      characterized preoperatively by more severely dilated left ventricle (end
      diastolic dimension 5.3 +/- 0.03 versus 1.6 +/- 3 S.D.) with decreased left
      ventricular wall thickness (1.19 +/- 0.7 versus 3.44 +/- 1.9 S.D.), decreased
      ratio between end diastolic wall thickness and end diastolic dimension (0.14 +/-
      0.06 versus 0.2 +/- 0.06) and a decreased velocity of shortening. Unlike the
      other 15 patients, the left ventricular function did not recover completely at
      mid term follow-up in those two patients. CONCLUSION: The Ross operation is a
      safe procedure and allows us to suppress completely the abnormal loading
      conditions of the left ventricle, resulting in a complete recovery of left
      ventricular function in most patients.

PMID- 9030796
TI  - Repair of aortic arch interruption by direct anastomosis.
AB  - OBJECTIVE: Evaluation of surgical treatment of interrupted aortic arch (IAA) by
      direct anastomosis. METHODS: A consecutive series of 17 infants with IAA (type A
      in eight patients, type B in nine) were operated upon. The mean age at arch
      repair was 1.0 month (range 0.2-7.7), mean weight was 3.7 kg (range 2.2-6.2). All
      arch repairs were done by direct anastomosis. This included a persistent arterial
      duct in one and a subclavian turnup in another case. The aortic reconstruction
      included reimplantation of a lusoric artery in three patients, patch enlargement
      of the ascending aorta in three and of the complete arch in one patient. The arch
      repair was done through a lateral thoracotomy in three patients. In 14 patients
      the aortic repair was part of a single-stage approach through a median sternotomy
      using cardiopulmonary bypass and circulatory arrest. RESULTS: There was no
      operative mortality. One patient (single-stage approach) died 2 days after
      operation due to respiratory problems caused by tracheobronchomalacy. One patient
      (lateral approach) died suddenly 3 months after aortic repair and banding. Median
      follow up was 4.8 years (range 0.1-12.9). In five patients restenosis of the
      aortic arch developed, all within 1.5 years after repair. This was not correlated
      with the type of interruption, weight at operation, age at operation or the
      surgical approach. The actuarial freedom from restenosis was 61% at 5 years with
      a 70% confidence limit (CL70%) of 46-75. All restenoses were balloon dilated, but
      two needed redo surgery, which was done by the median approach. In three patients
      discrete subaortic stenosis developed. This was not correlated with the type of
      interruption, weight at operation, age at operation or the surgical approach. The
      actuarial freedom from subaortic stenosis was 68% at 5 years (CL70% = 54-83).
      These stenoses were treated by enucleation, followed in one patient by a
      pulmonary autograft procedure for recurrent root stenosis after another year. At
      the end of follow up all patients were thriving well, lacked symptoms, were
      normotensive and had normal femoral artery pulsations. CONCLUSIONS: IAA can be
      treated well with primary anastomosis. Possible restenosis of the aortic arch can
      adequately be treated by percutaneous balloon dilatation or redo surgery if
      necessary. Arch repair by median single-stage approach has our preference.

PMID- 9030797
TI  - Pulmonary artery banding: adequacy and long-term outcome.
AB  - OBJECTIVE: Pulmonary artery banding remains a palliative option for patients with
      congenital heart disease and excessive pulmonary blood flow, if there is
      unfavourable anatomy or frail condition. In contrast to more developed countries,
      our patients at Red Cross Children's Hospital, Cape Town, often present to
      medical services late and in poor nutritional condition. We retrospectively
      reviewed patients undergoing pulmonary artery banding to determine major
      variables that influenced long-term outcome. METHODS: In a 10-year period ending
      June 1992, 135 consecutive patients underwent pulmonary artery banding; 89 with
      ventricular septal defect type non-mixing disorders, and 46 with mixing or
      complex disorders. The median age was 3.0 months and weight 3.5 kg with 74.8% of
      patients weighing less than the third percentile (NCHS adapted), and 39.3% had an
      additional serious medical illness. RESULTS: Pulmonary banding mortality was
      8.1%, and was higher in neonates (22.2%), P = 0.04) but was not related to
      congenital disorder, associated medical illness, or associated coarctation or
      interrupted aortic arch. The pulmonary band was inadequate at follow-up in 28.9%,
      which occurred more commonly if banding was necessary before 3 months of age
      (41.5%, P = 0.003) but was not related to weight, congenital disorder or
      associated respiratory infection. Sixty patients (44.4%) have now proceeded to
      definitive repair with a mortality of 23.3%, which was increased if the pulmonary
      band was inadequate at the time of definitive repair (44.4%: P = 0.02), but was
      not related to the congenital disorder. CONCLUSIONS: An inadequate pulmonary
      artery band adversely affects outcome and demands further aggressive management
      prior to definitive repair.

PMID- 9030798
TI  - Trial of pulmonary artery banding: a diagnostic criterion for 'one-stage'
      arterial switch in simple transposition of the great arteries beyond the neonatal
      period.
AB  - OBJECTIVE: Arterial switch operation (ASO) is the procedure of choice for the
      repair of simple d-transposition of the great arteries (TGA) during the neonatal
      period. Beyond this time such correction is performed in two stages. The first
      step incorporates banding of the pulmonary artery with or without a Blalock
      Taussig shunt to train the left ventricle (LV). The second step consists of the
      ASO. To find out whether candidates for a two-stage procedure would tolerate a
      one-stage correction, a trial of pulmonary artery banding was performed. MATERIAL
      AND METHODS: Between February 1986 and December 1995, 224 patients less than 3
      months of age with TGA, intact ventricular septum or a small restrictive
      ventricular septal defect, had an ASO. Seven patients were 4 weeks of age or
      older (28-70 days). Two of these had a pulmonary artery to systemic pressure
      ratio higher than 0.6 and underwent primary ASO without complications. The
      remaining five patients had low left ventricular pressure with a pulmonary to
      systemic pressure ratio of 0.2-0.5; echocardiography showed a banana-shaped LV
      with left ventricular wall thickness as low as 3 mm. They underwent a trial of
      pulmonary artery banding to systemic pressure for 15-30 min. As this increase in
      workload was tolerated well with an anticipated decrease of oxygen saturation but
      without hemodynamic disturbances anticipated, the ASO was performed immediately.
      RESULTS: Postoperative course was uneventful in all five patients, although
      catecholamine dependence was prolonged and three patients received enoximone.
      There were no severe complications. Echocardiography showed an increase in
      posterior wall thickness from 3 to 6 mm after 19 days in one infant. CONCLUSION:
      Some of the children, assigned for a 'two-stage' ASO may tolerate a primary
      anatomic repair up to an age of at least three months. This subgroup can be
      selected by a trial of pulmonary artery banding.

PMID- 9030799
TI  - Mechanical valve in aortic position is a valid option in children and
      adolescents.
AB  - OBJECTIVE: The choice of a valve substitute remains a challenge in young
      patients, with numerous reports of early degeneration and calcification of
      biological valves in this age group. Therefore an assessment of the long-term
      results after mechanical aortic valve replacement in children was initiated.
      METHODS: A retrospective study was conducted in 54 consecutive patients aged 1.1
      to 17 years (mean 12.8 +/- 4 years) operated on between 1975 and 1993. Aetiology
      was congenital in 34 patients, rheumatic in 13, infectious in 5, and dystrophic
      in 2. Concomitant surgery included mitral valve replacement (10), aortic annulus
      enlargement (9), correction of truncus arteriosus (7), Bentall operation (2),
      coarctation repair (2), tricuspid valvuloplasty (2), correction of double outlet
      right ventricle (1), and replacement of a right ventricle to pulmonary artery
      conduit (1). A Bjork-Shiley valve was implanted in 14 patients, and a St Jude
      Medical valve in 40. All patients were given Warfarin with a monthly INR control.
      Follow-up was completed through questionnaires mailed to referring physicians and
      direct clinical examination. RESULTS: Overall early mortality was 13% (7 cases),
      and 6% (2 cases) in the 32 patients operated on after 1984. Follow-up was
      complete in 45 survivors (2 lost to follow-up), with a total follow-up of 261
      patient-years. There were 6 late deaths, 4 being cardiac and due to persistent LV
      dysfunction, and 2 valve-related, due respectively to major gastro-intestinal
      bleeding and massive thromboembolism. Linearized rates of valve thrombosis and
      anticoagulant-related hemorrhage were both 0.3% per patient-year. Actuarial
      survival rate was respectively 84.5% at 5 years and 70.2% at 10 years.
      Reoperation was necessary in 3 patients for recurrent LV outflow tract
      obstruction. One patient with severe LV dysfunction is awaiting a heart
      transplant. CONCLUSION: We conclude that the longterm outcome after mechanical
      aortic valve replacement in children and adolescents is satisfactory and
      comparable to currently available reports on biological substitutes. The
      mandatory anticoagulant therapy is well tolerated in this age group.

PMID- 9030800
TI  - Comparison of myocardial revascularization without cardiopulmonary bypass to
      standard open heart technique in patients with left ventricular dysfunction.
AB  - OBJECTIVE: To compare myocardial revascularization without cardiopulmonary bypass
      to standard open heart technique in patients with left ventricular (LV)
      dysfunction. METHODS: 117 patients with LV dysfunction (ejection fraction (EF) <
      35%) underwent coronary artery bypass surgery between January 1991 and July 1994.
      Sixty-four (group A) were operated on without a cardiopulmonary bypass, and 53
      (group B) with one. Prevalence of EF < 20% (17 vs. 6%) and emergency operations
      (22 vs. 7%, P = 0.03) was higher in group A. The average number of grafts was 1.9
      +/- 0.8/pt in group A and 3.5 +/- 0.9/pt in group B (P < 0.01), and the internal
      mammary artery was used in 54 (84%) and 42 (79%) patients, respectively. Only 16
      patients (25%) in group A received a graft to a circumflex marginal artery
      compared to 51 (96%) in group B (P < 0.0001). RESULTS: Two patients (3.1%) died
      perioperatively in group A compared to 7 (13%) in group B (P = NS). In two
      patients from group A (3.1%) and in four (7.5%) from group B intra-aortic balloon
      pump was inserted postoperatively (P = NS). One year actuarial survival was 91
      and 79% (P = 0.03) and 2-year survival was 86 and 65% (P = 0.04), respectively.
      Return of angina occurred in five (8%) and three (6%) patients (P = NS).
      CONCLUSIONS: These results show a trend for lower operative risk resulting in
      better overall survival in selected patients with LV dysfunction undergoing
      coronary artery bypass surgery without cardiopulmonary bypass.

PMID- 9030801
TI  - Reoperative coronary artery bypass procedures: risk factors for early mortality
      and late survival.
AB  - OBJECTIVES: The number of coronary artery disease reoperations is increasing. The
      aim of this paper is to identify risk factors and evaluate the results of REDO
      coronary artery bypass grafting (CABG). MATERIAL: Between January 1984 and
      October 1994, 594 patients underwent REDO-CABG and 3157 underwent primary-CABG.
      The mean age was 62 years with 84% men. Hypertension, hyperlipidemia, insulin
      dependent diabetes, smoking and renal insufficiency were all more frequent in the
      REDO-group. A significantly higher number of patients undergoing REDO-CABG were
      in the Canadian Cardiovascular Society (CCS) angina class 3 and 4, had instable
      angina, had left main stem stenosis of greater than 70% and 3-vessel disease
      compared to those undergoing primary-CABG. The mean preoperative left ventricular
      function (LVEF) was 49.8 (REDO) vs. 58.2%, with a P value of less than 0.001.
      RESULTS: The overall postoperative mortality rate for REDO-operations was 9.6
      (57/594) vs. 2.8% for primary-CABG. Patients with a reoperative interval of more
      than 1 year had an 8.9% mortality rate, compared to those reoperated less than 1
      year after the initial CABG, where the mortality was 21% with a P value of less
      than 0.05. Postoperative low cardiac output syndrome, intraaortic balloon pump
      support, prolonged ventilatory support (> 24 h), hemorrhage and gastrointestinal
      complications were prominent features of the REDO-group (all P < 0.01). Urgent
      operation, CCS class 3 and 4, LVEF of less than 40%, generalized arteriosclerotic
      disease and advanced age (> 80 years) were independent risk factors for
      postoperative death in both groups. Preoperative renal insufficiency, diabetes
      and short interval from primary-CABG were added risk factors in the REDO-group.
      The 5-years survival rate after REDO-CABG was 89%, while the cardiac event-free
      survival rate was 79% and at 7 years 84 and 62%, respectively. CONCLUSIONS:
      Reoperative CABG is effective, but has an increased operative mortality and
      morbidity. The long-term results are encouraging. Unstable angina, poor
      preoperative left ventricular function, renal insufficiency, insulin dependant
      diabetes and an interval shorter than 1 year of the initial operation were
      independent riskfactors for mortality.

PMID- 9030802
TI  - Gastroepiploic artery coronary bypass graft: non-invasive patency evaluation
      using color and duplex Doppler ultrasonography.
AB  - OBJECTIVE: Color and duplex Doppler ultrasound and digital subtraction
      angiography were compared for the evaluation of graft patency of the
      gastroepiploic artery (GEA). METHODS: In 77 observations, ultrasound and digital
      subtraction angiography were compared. The coronary resistance index (cRI) was
      defined as the maximal systolic flow velocity minus the maximal diastolic flow
      velocity, divided by the maximal systolic flow velocity. On digital subtraction
      angiography, the graft was considered patent, occluded, or patent but non
      functional. Grafts were defined as non-functional when they had a diameter of
      less than 5F with the absence of opacification of the native coronary artery.
      RESULTS: Of the 77 observations, 64 GEAs were patent angiographically, three were
      occluded and ten grafts were considered as patent but non-functional. Using color
      and duplex ultrasound, the GEA was identified in 65 out of 77 observations. There
      were no cases of false positive visualization of the GEA. All sonographically
      detected non-functional grafts (n = 7) had a cRI of greater than 0.60. When the
      non-visualized grafts are considered either non-functional or occluded, a cut-off
      value for a cRI of 0.60 results in a sensitivity and specificity of 100 and 75%,
      respectively. CONCLUSION: We propose ultrasound as a primary screening tool for
      evaluating graft patency. While color Doppler is a suitable technique for graft
      visualization, spectral analysis with the calculation of a cRI is required for
      functional evaluation.

PMID- 9030803
TI  - Mid-term follow-up of 183 arterial myocardial revascularization procedures.
AB  - OBJECTIVE: To evaluate the mid-term results of complete arterial myocardial
      revascularization performed with arterial conduits. METHODS: From July 1987 to
      December 1994, 183 patients underwent a myocardial revascularization procedure
      with the use of at least two arterial grafts (IMAs, rGEA, IEA) at our institute.
      Their mean age was 56 +/- 8.7 years, the redo-operation rate was 16.9% (31/183),
      two-vessel disease was present in 61 patients (33.3%), three-vessel disease in
      122 (66.7%). RESULTS: The LIMA was used in 179 patients (97.8%), the RIMA in 116
      (63.4%), the rGEA in 66 (36.1%) and the IEA in 41 (22.4%). In-hospital mortality
      was 1.1% (2/183), while the perioperative myocardial infarction (MI) rate was
      2.2% (4/183). The angiographic restudy, performed on 87 (47.5%) patients during
      the early postoperative period (median 38 days) showed the following grafts
      patency rates: LIMA 98.8 (86/87), RIMA 97.1 (34/35), IEA 85.7 (24/28), rGEA 97.05
      (33/34) and saphenous vein 90.9% (10/11). The median follow-up was 35 months.
      Kaplan-Meier survival was 96 +/- 2% at 3 and 5 years, freedom from angina 94 +/-
      2% at 3 years and 91 +/- 3% at 5 years, while the Kaplan-Meier freedom from
      cardiac events was 90 +/- 3% at 3 years and 88 +/- 3% at 5 years. Cox regression
      analysis identified perioperative MI (P = 0.03, relative risk 3.6) as the only
      prognostic factor for mortality at follow-up. With regards to recurrence of
      angina, multivariate analysis has shown that incremental risk factors for the
      return of angina are redo-operation (P < 0.01, relative risk 2.7) and the
      persistence of hypertension after surgery (P < 0.01; relative risk 3.2), while
      the use of the RIMA in the operation has emerged as a protective factor (P =
      0.02; relative risk 0.43). Finally, only redo-operation (P < 0.01; relative risk
      2.3), has emerged as a predictor of cardiac complications. CONCLUSION: Myocardial
      revascularization with at least two arterial grafts can be performed with very
      low perioperative morbidity and mortality and good mid-term follow-up. The mid
      term results of arterial myocardial revascularization are less favourable in
      cases of redo-operations or when the RIMA is not used.

PMID- 9030804
TI  - Aprotinin and deep hypothermic circulatory arrest: there are no benefits even
      when appropriate amounts of heparin are given.
AB  - OBJECTIVE: To evaluate retrospectively the effect of 'high-dose' aprotinin on
      blood losses, donor blood requirements and morbid events on patients undergoing
      ascending aorta and/or aortic arch procedures with the employ of deep hypothermic
      circulatory arrest (HCA). METHODS: During the period 1987-1994, 39 patients
      underwent a thoracic aorta procedure with the employ of circulatory arrest; of
      these 18 (46.2%) were operated on during the period 1990-1994 and were given
      aprotinin intraoperatively following the 'high-dose' protocol (group I), while 21
      (53.8%) who underwent surgery during the years 1987-1989, did not receive
      intraoperative aprotinin and served as historical controls (group II). Twenty
      seven (69.2%) patients were male, 18 (46.2%) were operated on on an emergency
      basis, 15 (38.5%) were acute type A dissections, and two (5.1%) were redo
      operations. Circulatory arrest times were not significantly different between the
      two groups (40 +/- 4 (S.E.) group I vs. 43 +/- 4 min group II, P = 0.62) likewise
      cardiopulmonary bypass (CPB) times (181 +/- 9 vs. 201 +/- 20 mm, P = 0.74) and
      the amount of heparin administered (32056 +/- 1435 vs. 31 691 +/- 1935 IU, P =
      0.56). RESULTS: Postoperative blood loss was comparable between the two groups
      (1213 +/- 243 (median 850) group I vs. 1528 +/- 377 (median 880) ml group II, P =
      0.87), as well as the number of units of donor blood transfused (9.4 +/- 3.0
      (median 6) vs. 9.9 +/- 3.6, (median 5) P = 0.87), and revisions for bleeding
      (2/18, 11.1% vs. 3/21, 14.3%, P = 0.77). In-hospital mortality rate was not
      statistically different (5/18, 27.7% group I vs. 6/21, 28.6% group II, P = 0.92).
      There were no significant differences between the two groups in myocardial
      infarction (2/18, 11.1% vs. 0/21, 0%, P = 0.21), and postoperative renal failure
      rates (3/18, 16.7% vs. 2/21, 9.5%, P = 0.65). On the other hand, there was a
      trend towards an increased incidence of permanent neurological deficit (5/18,
      27.7% group I vs. 1/21, 4.8% group II, P = 0.07) and towards a more complicated
      postoperative course (perioperative renal failure and/or myocardial infarction
      and/or neurological deficit either transient or permanent) (8/18, 44.4% group I
      vs. 4/21, 19% group II, P = 0.09) in group I patients. Forward stepwise logistic
      regression analysis, performed on the whole group of patients, identified chronic
      obstructive pulmonary disease (P = 0.010, Odds ratio (OR) = 5.7), aprotinin use
      (P = 0.017, OR = 5.1), and the number of units of blood collected
      intraoperatively by the cellsaver (P = 0.045, OR = 1.3/unit) as independent
      predictors of complicated postoperative course in the whole group of patients.
      CPB time (P = 0.040, OR = 1.032/min), circulatory arrest time (P = 0.053, OR =
      1.22/min), and overall donor blood units transfused (P = 0.067, OR = 1.37/unit)
      emerged as independent risk factors for in-hospital mortality at multivariate
      analysis. CONCLUSIONS: Even when appropriate amounts of heparin are administered,
      'high-dose' aprotinin probably is not an effective blood-sparing drug in deep
      HCA. Aprotinin should be employed cautiously in this clinical setting because of
      its possible correlation with an increased rate of postoperative morbid events.

PMID- 9030805
TI  - Postoperative hemodynamics depend on cardiopulmonary bypass temperature: the
      potential role of endothelin-1.
AB  - OBJECTIVE: There is a growing body of evidence that perfusion temperature during
      cardiopulmonary bypass (CPB) influences postoperative systemic vascular
      resistance (SVR). The reason for this is not clear. Extracorporeal circulation
      can provoke raised plasma levels of endothelin-1 (ET-1), a very potent
      vasoconstrictor peptide produced by endothelial cells. We therefore analysed the
      effect of CPB temperature on postoperative vascular resistance and plasma
      concentrations of ET-1. METHODS: Thirty four patients undergoing elective
      coronary artery bypass grafting procedures were randomly assigned for either
      normothermic (37 degrees C, n = 17) or hypothermic CPB (28 degrees C, n = 17).
      Serial measurements of SVR and plasma ET-1 concentrations were performed before,
      during, and until 9 h after CPB measured. RESULTS: As a consequence of CPB,
      plasma ET-1 levels increased slightly in both groups. In normothermic patients,
      ET-1 reached maximal levels at the end of CPB whereas ET-1 levels in patients
      after hypothermic CPB had a tendency to further increase during the stay in the
      intensive care unit. Plasma ET-1 levels were significantly higher in patients 9 h
      postoperatively after hypothermic CPB (1.94 +/- 0.28 vs. 1.30 +/- 0.12 pg/ml, P =
      0.033), which was associated with significantly higher systemic vascular
      resistance index (SVRI) in these patients (area under the curve; 1978 +/- 76 vs.
      1626 +/- 69 dyne s/cm5 per m2, P = 0.003). Plasma ET-1 levels showed a positive
      correlation with postoperative SVRI (P = 0.008, r = 0.51) and a negative
      correlation with minimal rectal temperature during CPB (P = 0.006, r = 0.55).
      CONCLUSIONS: These results suggests that the hemodynamic differences after
      normothermic and hypothermic CPB might be mediated, at least in part, by
      temperature dependent changes in ET-1 plasma levels.

PMID- 9030806
TI  - Complement and neutrophil activation during cardiopulmonary bypass: a randomized
      comparison of hypothermic and normothermic circulation.
AB  - OBJECTIVE: Activation of both complement and neutrophils has been demonstrated to
      be involved in many pathological reactions following cardiopulmonary bypass
      (CPB). The aim of the present study is to evaluate the effect of normothermic and
      hypothermic CPB on both complement and neutrophil activation. METHODS: Two groups
      of patients (n = 20 each) scheduled for elective coronary artery bypass grafting,
      underwent CPB with intermittent warm or cold blood cardioplegia. Plasma
      concentration of C3a, C5a and C5b-9, as well as nitro-blu tetrazolium (NBT)
      scores of circulating neutrophils were measured before anesthesia, 10 and 30 min
      after the beginning of CPB, and 8, 16 and 24 h, postoperatively. RESULTS: In both
      groups, CPB determined a significant complement activation, evidenced as a
      significant increase in plasma concentration of C3a, C5a and C5b-9. This in turn
      triggered the neutrophil activation, documented as a significant increase of NTB
      scores in circulating neutrophils at the end of CPB and in the early
      postoperative period. Interestingly, in the warm group the extent of both
      complement and neutrophil activation was significantly higher compared with the
      cold group during the whole sampling period. CONCLUSION: In conclusion, our study
      clearly demonstrates that warm CPB is associated with an increased ability to
      activate complement and neutrophils in patients undergoing coronary surgery.

PMID- 9030807
TI  - Extraanatomic thoracic aortic bypass grafts: indications, techniques, and
      results.
AB  - OBJECTIVE: Even in the age of extensive aortic replacement special circumstances
      may warrant the insertion of extraanatomic thoracic aortic bypass grafts. Our
      experience with 17 patients is analyzed. METHODS: Between 1988 and 1994, ten
      female and seven male patients (mean age 37.5 years, range 9-69 years) were
      treated for the following indications: (1) complex CoA (n = 5); (2) reoperation
      for CoA (n = 6); (3) extensive aortic occlusive disease (n = 4); and (4)
      complicated aneurysm (n = 2). Routing of the grafts was: ascending-descending
      aorta (8); ascending-abdominal aorta (4); left subdavian artery- descending aorta
      (2); descending-descending aorta (2); and descending-abdominal aorta (1). Eight
      procedures were reoperations. In four patients concomitant cardiac operations
      were performed: one aortic valve replacement, one patch plasty of the LCA, and
      two composite graft replacements of aortic valve and ascending aorta, one of them
      with CABG. RESULTS: Three early deaths occurred. two after emergency operation in
      thoracic aneurysm under dire conditions (one perforation, one infection), one
      after ascending-abdominal aortic grafting with multiple branch revascularization.
      The underlying pathology was relieved successfully in all 14 survivors. In the
      two patients with concomitant aortic valve and isthmic stenosis, critical
      anterior motion of the mitral valve, presumably because of the massive afterload
      reduction of the left ventricle, complicated the perioperative course. One
      patient was reoperated because of aneurysm 4 years after descending-descending
      aortic grafting for complex CoA with poststenotic dilatation. CONCLUSIONS: In
      complex aortic coarctation or hypoplasia extraanatomic bypass grafts are
      expedient and effective procedures, especially for reoperation. Their use in the
      treatment of aneurysmal lesions remains an exception.

PMID- 9030808
TI  - The use of profound hypothermia and circulatory arrest in operations on the
      thoracic aorta.
AB  - OBJECTIVE: This retrospective study reviews the contemporary surgical outcome of
      our patients undergoing operations on thoracic aneurysms in deep hypothermic
      circulatory arrest. METHODS: Between January 1989 and February 1995, 279 patients
      were operated on in our institution on various portions of the aorta. In 143
      patients (97 male, 46 female), deep hypothermia and circulatory arrest were used
      as the standard operative technique. Patients age ranged from 16 to 83 years
      (mean 55). Final indication for operation was dissection Type A in 80 patients
      (61 acute, 19 chronic), dissection Type B in 21 patients (17 acute, 4 chronic)
      and atherosclerotic aneurysms in 42 patients (11 acute, 31 chronic). 16 patients
      were operated under preoperative unstable hemodynamic conditions, 6 patients had
      been resuscitated preoperatively. Surgical technique included cardiopulmonary
      bypass with femoral artery cannulation. For added cerebral protection all
      patients received Cortisone and barbiturates right before circulatory arrest
      (confirmed by 0-EEG). The segment of the aorta containing the area with the
      aneurysm, was resected and replaced with a tubular albumin coated graft. RESULTS:
      The 30-day mortality was 31.15% (19/61) in the acute and 23.52% (4/19) in the
      chronic type A dissection group, 35.29% (6/17) in the acute and 25% (1/4) in the
      chronic type B group, 36.3% (4/11) in the acute and 22.58% (7/31) in the chronic
      atherosclerotic group. Causes of postoperative death in order of frequency were:
      multiorgan failure (n = 15), myocardial failure (n = 13), bleeding (n = 4),
      sepsis (n = 4), myocardial infarction (n = 3) and stroke (n = 2). CONCLUSION:
      Despite rather high mortality rates in the acute aneurysm groups, the technique
      of profound hypothermic circulatory arrest represents a relatively safe method
      for operations on the thoracic aorta.

PMID- 9030809
TI  - The Concerted Action 'Heart' European registry on clinical application of
      mechanical circulatory support systems: bridge to transplant. The Registry
      Scientific Committee.
AB  - OBJECTIVE: The goal of this paper is to identify in the field of mechanical
      support as bridge to transplant, by statistical analysis, variables influencing
      survival during support (transplanted patients) and the overall survival
      (discharged after transplant). METHODS: Clinical factors are analysed in 258
      patients in the period 1986-1993. All variables were analyzed by a univariate and
      multivariate analysis. RESULTS: The indications for mechanically circulatory
      support were hemodynamic deterioration before transplantation in 177 (69%), post
      acute myocardial infarction in 40 (15%), postcardiotomy cardiogenic shock in 20
      (8%), graft failure in 12 (5%) and cardiac rejection 9 (3%). The devices
      implanted have been: pneumatic VAD in 145 cases (56%), electromechanical LVAS in
      15 cases (6%), TAH in 78 cases (30%) and centrifugal pumps in 20 cases (8%). The
      patients were supported for period ranging from 2 h to 623 days (mean 18.3 days
      +/- 43.2). The type of support was: LVAD 50 cases (20%), RVAD 3 cases (1%), BVAD
      127 cases (49%), and TAH 78 cases (30%). Bleeding occurred in 84 patients
      (32.5%), infections in 83 patients (32.1%); 21 embolic complications were
      reported in 16 patients (6%). Renal failure occurred in 64 cases (25%) requiring
      dialysis in 33 (13%); respiratory failure in 47 cases (18%); neurological
      impairment was noted in 22 patients (9%). One hundred-sixty patients were
      transplanted (62%) and 104 ultimately discharged (40% out of total 258 patients
      and 65% out of 160 transplanted patients). Among postoperative parameters, renal
      failure, TAH, neurological impairment and infection shown statistical power. Some
      pre- and post-operative variables were identified as independent risk factors for
      overall mortality: age, indication for graft failure, all indications different
      from cardiomyopathy, neurological impairment, renal insufficiency, infection,
      bleeding and any type of support different from LVAD. The improvement in the
      success rate in the last 2 years is statistically significant (P = 0.0282)
      considering both the percentage of transplanted patients and of discharged
      patients. CONCLUSIONS: The results are encouraging if mechanical support is
      performed in patients with deterioration while awaiting transplant, when LVAD is
      feasible and effective, when an ideal timing of transplant during support period
      is identified.

PMID- 9030810
TI  - The de-airing clamp in cardiac surgery.
AB  - De-airing of the heart in open heart surgery is a necessary routine. Most of the
      air is evacuated from the heart before the aortic cross clamp is removed, but the
      de-airing may be continued even after declamping. One way to continue de-airing
      is to partially clamp the ascending aorta, proximally to the aortic cannula, in
      order to create a pocket for trapping residual air coming from the left
      ventricle. This paper describes a clamp specially designed and developed for this
      purpose. It has been used in our center since 1990 and our experience is
      reported. The clamp has been used on 250 patients and in 50% ultrasonography has
      been used to examine the heart being free from air bubbles within 20 min from
      releasing the aortic cross clamp.

PMID- 9030811
TI  - Subglottic stenosis in an HIV positive patient: an exceptional form of clinical
      presentation in Kaposi's sarcoma.
AB  - The case of a 29-year-old HIV positive male patient suffering from a Kaposi's
      sarcoma exclusively located in the proximal third of the trachea and subglottic
      region is presented. The patient was found to have included an obstruction of the
      upper airway. A characteristic endoscopic appearance led to the final diagnosis.
      A combined treatment with Nd-YAG laser endoscopic resection and laringotracheal
      irradiation was performed. Pathological examination confirmed Kaposi's sarcoma.

PMID- 9030812
TI  - Reoperative aortic root surgery late after use of histo-acryl.
AB  - Cardiovascular reoperations after the use of histo-acryl are extremely rare. A
      patient is described, who underwent an aortic root replacement according to
      Bentall's technique, for a postdissectional aneurysm. At that time, to achieve
      hemostasis, histo-acryl adhesive was applied and a Cabrol's fistula was created.
      Fourteen years later, a recurrent 'false', aneurysm had developed and the fistula
      had a hemodynamically significant left-right shunt. At reoperation, the composite
      graft was replaced by a cryopreserved aortic root allograft with long coronary
      arteries. To our knowledge, this is the first report of a cardiovascular
      reoperation after previous use of histo-acryl. This patient also merits attention
      as to the fact that it illustrates a failure of a modified Cabrol's procedure.

PMID- 9030814
TI  - Polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes
      mellitus in the Russian population.
AB  - Recently, a polymorphism in the glycogen synthase gene was shown to be associated
      with the development of non-insulin-dependent diabetes mellitus (NIDDM) and
      identified patients with a strong family history of diabetes and hypertension in
      the Finnish population. However, no association was found in French and Japanese
      populations. We investigated the possible association between the XbaI
      polymorphism of the glycogen synthase gene and NIDDM in the Russian population.
      One hundred fifty NIDDM patients and 109 healthy controls were studied. In 16 of
      150 Russian NIDDM patients (10.7%), the XbaI polymorphism was found, and 17 of
      109 controls (15.6%) showed the XbaI polymorphism (P > .05). These results
      suggest that the XbaI polymorphism of the glycogen synthase gene cannot be used
      as a marker for NIDDM in the Russian population.

PMID- 9030813
TI  - Benign mesenchymoma of the esophagus.
AB  - Benign mesenchymoma is an extremely rare neoplasm mostly located in or about the
      kidney and is composed of a haphazard mixture of adult fat, fibrous tissue and
      tangled blood vessels, scattered nests or masses of smooth muscle cells,
      occasionally islands of cartilage, bone, and lymphoid tissue as well as other
      mesenchymal elements. Only two cases of benign mediastinal mesenchymomas were
      reported in the literature. In this report we describe a benign mesenchymoma of
      the mediastinum which presented itself with symptoms and signs of the traction
      diverticula of the esophagus.

PMID- 9030816
TI  - Hypothalamic-pituitary-adrenal axis hypersensitivity to naloxone in opioid
      dependence: a case of naloxone-induced withdrawal.
AB  - A case of opioid withdrawal precipitated in an opioid-dependent person by low
      plasma levels of naloxone is presented. In this patient, changes were observed in
      the hypothalamic-pituitary-adrenal (HPA) axis that preceded the clinical symptoms
      and adrenergic signs of withdrawal. Plasma naloxone levels were strongly
      correlated with plasma cortisol levels (P < .0001, R2 = .73, r = .85). In
      addition, these neuroendocrine changes persisted after adrenergic changes and
      clinical symptoms had been ameliorated by administration of a short-acting opioid
      agonist. It is suggested that the HPA axis is a more sensitive indicator of
      opioid withdrawal than the adrenergic system.

PMID- 9030815
TI  - Visceral adipose tissue impairs insulin secretion and insulin sensitivity but not
      energy expenditure in obesity.
AB  - In obesity, a central pattern of fat distribution is mostly associated with
      hyperinsulinemia, insulin resistance, and hyperlipemia, thus promoting the
      development of non-insulin-dependent diabetes mellitus and cardiovascular
      disease. In addition, in obesity, changes in energy expenditure are hypothesized
      to be involved in the development or maintenance of excessive body fat storage.
      In this study, abdominal fat distribution by computed tomographic (CT) scan was
      used to study the relation between the visceral fat depot, insulin secretion, and
      insulin sensitivity in a group of obese subjects with normal glucose tolerance (n
      = 26; body mass index [BMI], 39 +/- 1 kg/m2) and a group of normal-weight control
      subjects (n = 9; BMI, 23 +/- 1 kg/m2). The minimal model method was used to
      assess insulin sensitivity, S(I), and first-phase (phi1) and second-phase (phi2)
      beta-cell sensitivity from plasma glucose, insulin, and C-peptide concentrations
      measured during an intravenous glucose tolerance test ([IVGTT] 0.33 g/kg body
      weight). Moreover, we evaluated the relationships between these parameters and
      the resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) measured
      by indirect calorimetry. The data show the following: (1) in obese subjects, phi1
      is greater but not statistically different from the value in control subjects
      (252 +/- 41 v 157 +/- 25 dimensionless 10(9)); (2) phi2 is significantly higher
      in obese subjects (27 +/- 4 v 14 +/- 2 min(-1) x 10(9), P < .05), with a positive
      correlation between the amount of visceral adipose tissue (VAT) and phi2 (r =
      .49, P < .05); (3) S(I) is decreased in the obese group (2.8 +/- 0.3 v 9.7 +/-
      1.6 10(-4) x min(-1)/microU x mL(-1)), P < .0001), with a negative correlation of
      S(I) with the adiposity index BMI (r = -.67, P < .0001) and VAT (r = .56, P <
      .05); (4) RMR, expressed in absolute terms, was significantly increased in obese
      versus lean subjects (5.9 +/- 0.2 v 4.6 +/- 0.3 kJ/min, P < .01), whereas when
      RMR was adjusted for fat-free mass (FFM), the difference between the two groups
      disappeared (0.09 +/- 0.003 v 0.09 +/- 0.002 kJ/min x kg FFM). We did not observe
      any difference in GIT between lean and obese subjects. Moreover, GIT was
      significantly correlated with FFM (r = .69, P < .005), but not with BMI. The
      amount of VAT did not correlate with RMR or GIT. In conclusion, these results
      suggest that in obese subjects with normal glucose tolerance, insulin sensitivity
      is impaired and the beta-cell hyperresponse to glucose is mainly due to an
      enhanced second-phase beta-cell secretion. The degree of visceral fat deposition
      seems to affect insulin secretion and worsens insulin sensitivity, but does not
      influence energy expenditure.

PMID- 9030817
TI  - Clofibrate feeding to Sprague-Dawley rats increases endogenous biosynthesis of
      oxalate and causes hyperoxaluria.
AB  - The effects of clofibrate feeding (5 g/kg diet) on oxalate metabolism were
      investigated in male and female rats. Following clofibrate feeding, 24-hour
      urinary excretion of oxalate increased until 4 days and then reached a plateau.
      Whereas the contribution of dietary oxalate (1.4 g/kg diet, as potassium salt) to
      urinary oxalate was less than 5% in both control and clofibrate-treated male
      rats, the contribution of dietary glycolate (1.0 g/kg diet, as sodium salt) to
      urinary oxalate was six times higher in clofibrate-treated male rats compared
      with controls, indicating that the clofibrate-induced hyperoxaluria is due to
      increased endogenous biosynthesis of oxalate. This was supported by the increased
      lactate dehydrogenase (LDH) activity observed in liver supernatants of clofibrate
      treated rats compared with controls, and the increased rate of conversion of
      glycolate and glyoxylate to oxalate by clofibrate-treated male rat liver
      supernatants. Female rats had lower excretion of urinary oxalate and lower levels
      of liver glycolic acid oxidase (GAO) as compared with males. Clofibrate-treated
      female rat liver supernatants had higher LDH levels and produced more oxalate
      from glyoxylate. Thus, it can be concluded that the increase in LDH activity may
      be the cause of the increased endogenous biosynthesis of oxalate leading to
      increased urinary excretion of oxalate in male and female rats treated with
      clofibrate.

PMID- 9030818
TI  - Insulin secretion, glucose production, and insulin sensitivity in underweight and
      normal-weight volunteers, and in underweight and normal-weight cancer patients: a
      Clinical Research Center study.
AB  - Severe malnutrition (< 65% ideal body weight [IBW]) is associated with reduced
      insulin secretion, decreased receptor affinity, and glucose intolerance. To
      characterize the abnormality of mild malnutrition in terms of insulin action,
      both the insulin sensitivity index and insulin secretion were measured in 15
      underweight and 15 normal-weight volunteers. Ten patients had localized squamous
      cell carcinomas of the head and neck, and 20 were normal controls. After a 10
      hour overnight fast, all volunteers were studied using Bergman's modified
      intravenous (IV) glucose tolerance test (IVGTT). Body weight and diagnosis were
      compared using a 2 x 2 ANOVA. The acute insulin response to IV glucose was
      reduced in normal-weight and underweight cancer patients by approximately 40% to
      50% (P < .05). Both groups of cancer patients had a significantly reduced rate of
      glucose disposal (1.25 +/- 0.29 and 1.27 +/- 0.23 %/min) compared with the
      healthy volunteers (1.82 +/- 0.21 and 1.81 +/- 0.24 %/min, respectively, P <
      .05). Glucose production (GP) was significantly increased in the underweight
      cancer patients versus the weight-matched volunteers (13.9 +/- 1.3 v 10.8 +/- 0.5
      micromol/kg/min, P < .05). Normal-weight and underweight cancer patients had a
      32% to 44% reduction in insulin sensitivity (P < .05). In contrast to the effects
      of cancer, underweight controls had twice the insulin sensitivity compared with
      normal-weight controls (P < .01). Since insulin secretion decreased in
      underweight controls, the increased insulin sensitivity may have been due to an
      increased insulin action and to factors associated with leanness.

PMID- 9030820
TI  - Pituitary neuromedin B content in experimental fasting and diabetes mellitus and
      correlation with thyrotropin secretion.
AB  - Fasting and diabetes mellitus in the rat model have been associated with
      abnormalities of thyrotropin (TSH) secretion. Neuromedin B is a bombesin-like
      peptide highly concentrated in the pituitary gland that has been shown to have
      inhibitory action on TSH secretion, acting as an autocrine/paracrine factor.
      Here, we aimed to determine if the pituitary content of neuromedin B would change
      in fasted rats (1, 2, 3, and 4 days of food deprivation) and streptozotocin (55
      mg/kg body weight)-diabetic rats. The total pituitary content of neuromedin B was
      decreased in fasted rats, except at 2 days of fasting, as was the total protein
      content in the gland; however, the concentration of the peptide (femtomoles per
      milligram protein) did not significantly change until the fourth day of food
      deprivation, when an abrupt decrease in total protein happened and therefore
      neuromedin B concentration increased. In rats after 20 days of diabetes
      induction, pituitary neuromedin B increased. Serum thyroxine (T4) and
      triiodothyronine (T3) decreased in both disorders, whereas serum TSH was normal
      or decreased in 4-day fasted rats. Therefore, the caloric deprivation of diabetes
      and fasting changed the pituitary neuromedin B content and concentration, by
      mechanisms that remain to be elucidated. Since neuromedin B has been shown to act
      as a local inhibitor of TSH release, the results raise the possibility that
      increased neuromedin B concentration might be involved in the altered TSH
      secretion of diabetes mellitus and fasting.

PMID- 9030819
TI  - Characterization of low-density lipoprotein subclasses in children.
AB  - Low-density lipoprotein (LDL) particles are heterogeneous in density, size, and
      chemical composition, and this heterogeneity is thought to be genetically
      influenced. In the present study, plasma LDL subclasses in 248 children aged 7 to
      13 years were analyzed by gradient gel electrophoresis. The prevalence of small
      dense LDL (SDLDL), a potent atherogenic LDL, was 9.3%, which is lower than that
      reported in adults. Furthermore, children with this LDL subclass showed increased
      body fatness and dyslipidemia, including elevated plasma triglyceride and
      apolipoprotein (apo) B concentrations and decreased plasma high-density
      lipoprotein (HDL) cholesterol and apo A-I concentrations, compared with children
      without this phenotype. These findings suggest that in addition to genetic
      factors, environmental factors that affect these cardiovascular risk factors may
      also influence expression of the SDLDL subclass.

PMID- 9030821
TI  - Regulation of thyroid hormones in the secretion of insulin and gastric inhibitory
      polypeptide in male rats.
AB  - The effect of thyroid hormones on glucose-induced secretion of gastric inhibitory
      polypeptide (GIP) and insulin was studied. Male rats were thyroidectomized (Tx)
      or sham Tx. Sham Tx rats were injected with either propylthiouracil ([PTU] 20
      mg/kg intraperitoneally) or saline for 2 weeks. In addition, thyroid-intact rats
      were injected intravenously with triiodothyronine ([T3]5 microg/kg) or saline 10
      minutes before an oral glucose load (3.2 g/kg). Blood samples were collected from
      each animal via a jugular catheter at 0, 10, 20, 30,45, 60, and 90 minutes
      following glucose ingestion. Plasma levels of GIP and insulin were measured by
      specific radioimmunoassays (RIAs). Thyroidectomy-induced hypothyroidism increased
      the basal level of plasma GIP, but decreased that of insulin. Insulin levels at
      10, 20, and 30 minutes following oral glucose were lower in hypothyroid rats than
      in euthyroid rats. Conversely, GIP levels at 60 and 90 minutes following glucose
      ingestion in PTU-induced hypothyroid rats were higher than those in euthyroid
      rats. Furthermore, glucose-stimulated insulin secretion was unaltered by
      pretreatment with T3, whereas the glucose-induced increase in plasma GIP was
      completely abolished by preinjection of T3 in thyroid-intact rats. These results
      suggest that thyroid functions are involved in the regulation of insulin and GIP
      secretion in rats.

PMID- 9030822
TI  - Insulin resistance in limb and trunk partial lipodystrophy (type 2 Kobberling
      Dunnigan syndrome).
AB  - We studied insulin action in two patients with limb and trunk partial
      lipodystrophy with hirsutism and acanthosis nigricans. Glucose was normal in one
      of the patients and slightly above normal in the other during an oral glucose
      tolerance test (OGTT). An intravenous glucose tolerance test (IVGTT) was normal
      in both patients. Basal and glucose-stimulated insulin levels were elevated in
      both the OGTT and IVGTT in both patients. The response of plasma glucose to
      exogenously administered insulin was decreased. A euglycemic-hyperinsulinemic
      clamp performed in patient no. 2 indicated insulin resistance, which was not
      corrected by reducing the increased basal level of serum free fatty acids (FFAs).
      Binding of insulin to neck adipocytes was normal in both subjects, but glucose
      transport and oxidation in these cells was impaired. Insulin binding to abdominal
      adipocytes was increased in one patient whose adipocytes displayed higher glucose
      transport at low insulin concentrations. Glucose oxidation was decreased in
      abdominal adipocytes of both patients. We conclude that insulin resistance in
      Kobberling-Dunnigan type 2 partial lipodystrophy is not related to an alteration
      of the insulin molecule or to changes in insulin binding, but is more likely
      associated with a postreceptor defect, since glucose oxidation was impaired in
      adipocytes of the neck and abdomen.

PMID- 9030823
TI  - Splanchnic versus whole-body production of alpha-ketoisocaproate from leucine in
      the fed state.
AB  - The extent to which dietary branched-chain amino acids are deaminated by the
      splanchnic tissues (ie, the liver and gut) in the fed state and released as
      ketoacids into the systemic circulation is not known. To determine this, we
      combined the oral (L-[1-13C]-leucine, [13C]-Leu) and intravenous (L-[5,5,5
      2H3]leucine, [2H3]-Leu) leucine tracer infusion with the intravenous
      administration of an independent isotope of the leucine ketoanalog alpha
      ketoisocaproic acid (KIC) ([4,5-3H]KIC). The study was conducted during constant
      administration of a complete mixed meal. We found that 26% +/- 5% of the orally
      administered leucine was taken up by the splanchnic organs at first pass, whereas
      74% +/- 5% appeared in the systemic circulation. The rate of splanchnic KIC
      release from deamination of dietary leucine accounted for 3% +/- 0.2% of the oral
      leucine administration rate and 13% +/- 2% of leucine splanchnic uptake
      (fractional splanchnic deamination). The fraction of whole-body total leucine
      uptake that was deaminated to KIC was 41% +/- 5% (P < .05 v fractional splanchnic
      deamination of dietary leucine uptake). We conclude that (1) the release of KIC
      from leucine deamination within splanchnic tissues constitutes a minimal fraction
      of first-pass dietary leucine uptake, and (2) splanchnic tissues are relatively
      less efficient than the whole body in KIC production from leucine deamination.

PMID- 9030825
TI  - Insulin sensitivity, glucose effectiveness, and beta-cell function in obese males
      with essential hypertension: investigation of the effects of treatment with a
      calcium channel blocker (diltiazem) or an angiotensin-converting enzyme inhibitor
      (quinapril).
AB  - It has been suggested that hyperinsulinemia secondary to insulin resistance may
      be a pathogenetic factor common to obesity, non-insulin-dependent diabetes
      mellitus (NIDDM), and hypertension. Furthermore, beta-blockers and thiazide
      diuretics have been shown to be capable of increasing insulin resistance and thus
      of inducing NIDDM in predisposed individuals. We used the minimal model approach
      (MMA) to glucose metabolism and insulin kinetics to compare peripheral insulin
      sensitivity and beta-cell function in hypertensive and normotensive obese men.
      The hypertensive group consisted of 37 obese men with mild to moderate
      hypertension; following a drug-free period of 4 weeks, 20 of these subjects
      received diltiazem and 17 quinapril over the 12-week study period. The
      normotensive (control) group contained 17 obese men without microalbuminuria,
      dyslipidemia, or a family history of essential hypertension or NIDDM. Before and
      at the end of the 12-week study period, subjects underwent frequently sampled
      intravenous glucose tolerance (FSIGT) tests. The results were used to estimate an
      insulin sensitivity index (S(I)), a glucose effectiveness index (S(G)), and beta
      cell sensitivity to glucose indices during first- and second-phase insulin
      secretion (phi1 and phi2) using the minimal models of glucose metabolism and
      insulin kinetics. No significant differences in S(I) or S(G) were detected
      between the hypertensive and control groups. Twelve weeks' treatment with
      diltiazem led to a slight but significant increase in phi1; however, neither
      diltiazem nor quinapril had significant effects on S(I) or S(G). We conclude that
      men with obesity and hypertension have no greater insulin resistance than those
      with obesity alone, suggesting that hypertension is not generally associated with
      any significant increase in insulin resistance. Treatment with diltiazem or
      quinapril does not have undesirable effects on glucose metabolism. However,
      treatment with diltiazem led to a significant increase in beta-cell sensitivity
      to glucose; this is of particular interest, given the importance of phi1 for
      peripheral glucose uptake.

PMID- 9030826
TI  - Evidence for sex steroid inhibition of lipoprotein lipase in men: comparison of
      abdominal and femoral adipose tissue.
AB  - Plasma estradiol has been suggested to suppress adipose tissue lipoprotein lipase
      (LPL) activity in women. The present study explores the regulation of LPL by sex
      steroids in sedentary obese men (N = 24) at their usual weight. Femoral adipose
      tissue LPL activity, eluted with serum and heparin or extracted with detergent,
      showed significant inverse correlations with plasma levels of testosterone,
      bioavailable testosterone, dihydrotestosterone, and estradiol. Both measures of
      femoral LPL activity were also correlated with the weight change occurring
      despite efforts to maintain a constant weight. Abdominal LPL activity showed
      significant but weaker inverse correlations with bioavailable testosterone only.
      Multivariate analysis of potential predictors for eluted femoral LPL activity
      showed that plasma testosterone, dihydrotestosterone, and estradiol were
      interdependent, whereas the rate of weight change was an independent variable. In
      the regression equation, only bioavailable testosterone and weight change were
      retained, explaining 63% of the variability (R = .79, P = .0002). These results
      suggest that sex steroids suppress adipose tissue LPL activity in men, and more
      so in the thigh than in the abdomen, thereby possibly contributing to a central
      fat accumulation. The data are compatible with a model from male animals
      suggesting that testosterone effects on adipose tissue LPL are mediated by
      estradiol formed locally.

PMID- 9030824
TI  - Decreased myocardial glucose uptake during ischemia in diabetic swine.
AB  - The purpose of the study was to assess myocardial glucose uptake in nondiabetic
      (n = 5) and streptozotocin-diabetic (n = 6) Yucatan miniature swine under matched
      hyperglycemic and hypoinsulinemic conditions. Fasting conscious diabetic swine
      had significantly higher plasma glucose levels (20.9 +/- 2.6 v 5.2 +/- 0.3
      mmol/L) and lower insulin levels (6 +/- 1 v 14 +/- 4 microU/mL) than nondiabetic
      animals. Myocardial glucose uptake was measured in open-chest anesthetized
      animals under aerobic and ischemic conditions 12 weeks after streptozotocin
      treatment. Coronary blood flow was controlled by an extracorporeal perfusion
      circuit. Ischemia was induced by reducing left anterior descending (LAD) coronary
      artery blood flow by 60% for 40 minutes. Animals were treated with somatostatin
      to suppress insulin secretion, and nondiabetic swine received intravenous (IV)
      glucose to match the hyperglycemia in the diabetic animals. The rate of glucose
      uptake by the myocardium was not statistically different under aerobic
      conditions, but was significantly lower in diabetic swine during ischemia (0.20
      +/- 0.08 v 0.63 +/- 0.14 micromol x g(-1) x min(-1), P < .01). Myocardial glucose
      transporter (GLUT4) protein concentration was decreased by 31% in diabetic swine.
      In conclusion, 12 weeks of streptozotocin diabetes in swine caused a significant
      decrease in myocardial GLUT4 protein and a decrease in myocardial glucose uptake
      during ischemia.

PMID- 9030827
TI  - Differences in the concentration and composition of low-density lipoprotein
      subfraction particles between sedentary and trained hypercholesterolemic men.
AB  - There is evidence that a low-density lipoprotein (LDL) subfraction profile of
      increased concentrations of small, dense LDL particles is less common among
      trained than among sedentary normocholesterolemic men, but it is still uncertain
      whether there is a similar association in hypercholesterolemia also. Therefore,
      we determined the lipid and apolipoprotein concentration and composition of six
      LDL subfractions (density gradient ultracentrifugation) in 20 physically fit,
      regularly exercising (>three times per week) hypercholesterolemic men and 20
      sedentary hypercholesterolemic controls. Trained (maximal oxygen consumption
      [VO2max], 57.3 +/- 7.4 mL/kg/min) and sedentary (VO2max, 37.5 +/- 8.8 mL/kg/min)
      individuals (aged 35 +/- 11 years; body mass index [BMI], 23.9 +/- 2.7 kg/m2)
      were matched for LDL apolipoprotein (apo) B levels (108 +/- 23 and 112 +/- 36
      mg/dL, respectively). Trained subjects had significantly lower serum triglyceride
      (P < .05) and very-low-density lipoprotein (VLDL) cholesterol levels (P < .05)
      and higher high-density lipoprotein 2 (HDL2) cholesterol levels (P < .01) than
      sedentary controls. LDL particle distribution showed that trained individuals had
      significantly less small, dense LDL (d = 1.040 to 1.063 g/mL) and more large LDL
      (d = 1.019 to 1.037 g/mL) subfraction particles than sedentary controls, despite
      equal total LDL particle number. Analysis of LDL composition showed that LDL
      particles of hypercholesterolemic trained men had a higher free cholesterol
      content than LDL of untrained hypercholesterolemic men. Small, dense LDL in
      hypercholesterolemic trained men were richer in phospholipids than those in
      sedentary controls. These data demonstrate the significant influence of aerobic
      fitness on lipoprotein subfraction concentration and composition, thereby
      emphasizing the role of exercise in the treatment and risk reduction of
      hypercholesterolemia.

PMID- 9030829
TI  - Prevalence of the Trp64Arg missense mutation of the beta3-adrenergic receptor
      gene in Japanese subjects.
AB  - Prompted by the recent findings that a tryptophan to arginine (Trp64Arg) mutation
      in the beta3-adrenergic receptor gene was associated with an earlier onset of non
      insulin-dependent diabetes mellitus (NIDDM) in Pima Indians, with abdominal
      obesity and insulin resistance in Finns, and with an increased capacity to gain
      weight in French whites, we studied the prevalence of this mutation in 231
      diabetic and 95 nondiabetic Japanese subjects and assessed its contribution to
      the development of obesity and NIDDM. The allelic frequencies of the mutation
      were 0.18 in diabetic and 0.23 in nondiabetic subjects, showing no significant
      difference between the two groups (P = .067). In nondiabetic subjects, body mass
      index (BMI) did not differ between those with and without the mutation (22.2 +/-
      3.5 v 21.4 +/- 3.2 kg/m2, P = .252). In NIDDM subjects, BMI at the time of study
      and maximal BMI before the start of treatment did not differ between those with
      and without the mutation (22.8 +/- 2.6 v 23.2 +/- 3.7 kg/m2, P = .678, and 24.7
      +/- 2.6 v 24.9 +/- 3.1 kg/m2, P = .277). Homozygotes for the mutation did not
      have trends to have increased BMI in either diabetic or nondiabetic subjects. The
      age at diagnosis of NIDDM also did not differ between the two groups (48.8 +/-
      9.9 v 47.8 +/- 12.5 years, P = .796). Fasting serum cholesterol and triglyceride
      levels and systolic and diastolic blood pressure before the start of treatment
      did not differ between NIDDM subjects with and without the mutation. In
      conclusion, although the Trp64Arg mutation is not uncommon in Japanese, it does
      not appear to be associated with obesity, NIDDM, age at diagnosis of NIDDM, or
      dyslipidemia. Our results suggest that the mutation has minor effects, if any, on
      the development of obesity and NIDDM in Japanese.

PMID- 9030828
TI  - Metabolic effects of troglitazone in the Goto-Kakizaki rat, a non-obese and
      normolipidemic rodent model of non-insulin-dependent diabetes mellitus.
AB  - Troglitazone (TRG) is an orally active antidiabetic agent that increases insulin
      sensitivity in models of non-insulin-dependent diabetes mellitus (NIDDM),
      subsequently reducing hyperinsulinemia and hyperglycemia. We examined the effects
      of TRG on the development and severity of diabetes in the Goto-Kakizaki (GK) rat,
      a spontaneous, non-obese model of NIDDM. TRG was administered at a dose of 30
      mg/kg/d beginning at 4 weeks of age. TRG-treated GK rats were evaluated against
      Wistar and untreated GK rats at 8, 12, and 16 weeks of age. Untreated GK rats
      were nonketotic, normolipidemic, hyperglycemic, and had normal fasting insulin
      levels compared with Wistar rats. TRG treatment decreased glycosylated hemoglobin
      levels in the GK rat independently of its effects on plasma insulin. In untreated
      GK rats, intravenous glucose tolerance tests (IVGTTs) showed a hyperglycemic
      response to glucose loading with severely impaired glucose disposal relative to
      Wistar controls. TRG treatment was successful in decreasing the glucose area
      under the curve (AUC) (P < .03) but did not improve glucose disposal, suggesting
      a direct hepatic effect. Ex vivo evaluation of hepatic glucose output (HGO)
      further supported a direct hepatic action, with 50% reduction in HGO in TRG
      treated GK rats (P < .004). A euglycemic-hyperinsulinemic clamp performed at 16
      weeks of age showed severe insulin resistance in the untreated GK rat, with a
      glucose infusion rate (GIR) 33% lower than in Wistar rats (P < .004). TRG
      treatment had no effect on this insulin resistance. These results indicate that
      TRG selectively decreases hepatic glucose production in this unique model of
      NIDDM independently of its action on peripheral insulin sensitivity or
      hyperlipidemia.

PMID- 9030830
TI  - Influence of moderate physical exercise on insulin-mediated and non-insulin
      mediated glucose uptake in healthy subjects.
AB  - To establish the relative importance of insulin sensitivity and glucose
      effectiveness during exercise using Bergman's minimal model, 12 nontrained
      healthy subjects were studied at rest and during 95 minutes of moderate exercise
      (50% maximum oxygen consumption [VO2max]). Each subject underwent two frequently
      sampled intravenous glucose tolerance tests (FSIGTs) for 90 minutes, at rest
      (FSIGTr) and during exercise (FSIGTe). Plasma glucose, insulin, and C-peptide
      were determined. Insulin sensitivity (S(I)), glucose effectiveness at basal
      insulin (S(G)), insulin action [X(t)], and first-phase (phi1) and second-phase
      (phi2) beta-cell responsiveness to glucose were estimated using both minimal
      models of glucose disposal (MMg) and insulin kinetics (MMi). Glucose
      effectiveness at zero insulin (GEZI), glucose tolerance index (K(G)), and the
      area under the insulin curve (AUC(0-90)) were also calculated. Intravenous
      glucose tolerance improved significantly during physical exercise. During
      exercise, S(I) (FSIGTr v FSIGTe: 8.5 +/- 1.0 v 25.5 +/- 7.2 x 10(-5) x min(-1)
      [pmol x L(-1)]-1, P < .01), S(G) (0.195 +/- 0.03 v 0.283 +/- 0.03 x 10(-1) x min(
      1), P < .05), and GEZI (0.190 +/- 0.03 v 0.269 +/- 0.04 x 10(-1) x min(-1), P <
      .05) increased; however, no changes in phi1 and phi2 were found. Despite a
      significant decrease in the insulin response to glucose (AUC0-90, 21,000 +/-
      2,008 v 14,340 +/- 2,596 pmol x L(-1) x min, P < .01), insulin action [X(t)] was
      significantly higher during the FSIGTe. These results show that physical exercise
      improves mainly insulin sensitivity, and to a lesser degree, glucose
      effectiveness. During exercise, the insulin response to glucose was lower than at
      rest, but beta-cell responsiveness to glucose did not change.

PMID- 9030831
TI  - Growth hormone secretion and synthesis are depressed in obesity-susceptible
      compared with obesity-resistant rats.
AB  - Human obesity is characterized by a low basal growth hormone (GH) concentration
      and a blunted response to GH secretagogues. The aim of this experiment was to
      determine whether a perturbation in GH synthesis or secretion occurs in rats that
      develop obesity only in response to a dietary fat challenge. Female Sprague
      Dawley rats were fed a purified 32.5% fat diet ad libitum for 21 weeks.
      Approximately half of the rats fed this diet developed obesity (obesity
      susceptible) while the others remained lean (obesity-resistant) compared with
      chow-fed (control) animals. Pituitary glands obtained from all three groups were
      enzymatically dissociated, and somatotrope response to GH secretagogues and
      inhibitors was determined in vitro. Plasma GH concentrations were decreased in
      obesity-susceptible rats compared with obesity-resistant rats, and in vitro GH
      secretory response was blunted in cells obtained from the pituitary glands of
      obese compared with lean rats. In addition, pituitary GH content was reduced in
      obese versus lean rats even though the proportion of somatotropes in the two
      groups did not differ. Since the changes in GH concentration in this dietary
      obese rat model parallel those found in human obesity, this model may be useful
      in determining the relationship between GH and obesity.

PMID- 9030832
TI  - Effect of prolonged exercise training without weight loss on high-density
      lipoprotein metabolism in overweight men.
AB  - This study examined the effect of exercise training without weight loss on high
      density lipoprotein (HDL) metabolism in overweight men. We evaluated HDL
      metabolism using 125I-radiolabeled autologous HDL in 17 overweight men aged 40 +/
      7 years (mean +/- SD) before and after 1 year of exercise training. Subjects
      consumed defined diets in a metabolic kitchen during the metabolic studies. They
      performed endurance exercise under supervision for 1 hour four times weekly and
      maintained their pretraining body weight. Maximal oxygen uptake (VO2max)
      increased 27% (P < .001) with exercise training. HDL-cholesterol (HDL-C) and
      apolipoprotein (apo) A-I increased 10% and 9%, respectively (P < .001 for both),
      whereas triglycerides and apo B decreased 7% and 10%, respectively (P < .05).
      Postheparin lipoprotein lipase increased 11% (P = NS). Hepatic triglyceride
      lipase activity (HTGLA) decreased 12% (P < .05). The fractional catabolic rate
      (FCR) of HDL protein and of apo A-I decreased 5% and 7%, respectively (P < .05
      for both). The synthetic rate of apo A-I increased 13% (P < .01). Increased HDL
      after exercise training is associated with both decreased HDL protein catabolism
      and increased HDL apo A-I synthesis. Weight loss is not required to increase HDL
      C with exercise training in overweight men, but without weight loss, even
      prolonged exercise training produces only modest changes in HDL-C concentrations.

PMID- 9030833
TI  - Vitamin D receptor alleles do not correlate with bone mineral density in
      premenopausal Caucasian women from the southeastern United States.
AB  - Genetic factors are important in determining peak bone density. Recent studies
      indicate that polymorphisms of the vitamin D receptor (VDR) may account for much
      of the genetic contribution to bone density, and VDR genotype may be useful to
      predict the risk of developing osteoporosis. However, the association between VDR
      genotype and bone mineral density (BMD) has not been observed in all populations.
      We determined VDR genotype in 69 healthy premenopausal Caucasion women from the
      southeastern United States and measured BMD at the lumbar spine (anterior
      posterior [AP] and lateral views) and proximal femur. We found no association
      between VDR genotype and BMD at any site. Our results indicate that in this
      population, VDR genotype does not predict peak bone density and should not be
      used to predict the risk of developing osteoporosis.

PMID- 9030834
TI  - Effects of metformin on the pathways of glucose utilization after oral glucose in
      non-insulin-dependent diabetes mellitus patients.
AB  - To analyze the effects of metformin (M) on the kinetics and pathways of glucose
      utilization after glucose ingestion, nine non-insulin-dependent diabetes mellitus
      (NIDDM) patients underwent two 5-hour oral glucose tolerance tests (OGTTs)
      preceded in random order by a 3-week treatment with either M (850 mg twice per
      day) or placebo. Each test included intravenous infusion of 3-3H-glucose and
      labeling of the oral dose (75 g) with 1-14C-glucose, with measurements of glucose
      kinetics, glycolytic flux (3H2O production), and glucose oxidation (indirect
      calorimetry and expired 14CO2). Basal glycemia was decreased by M (6.6 v 8.2
      mmol/L, P < .01) with no changes in insulin levels, with the hypoglycemic effect
      correlating strongly (P < .001) with a decrease in glucose production. Mean 0- to
      5-hour postprandial glycemia was also decreased by the drug (9.9 v 12.2 mmol/L, P
      < .04), lactate concentration was increased (1.79 v 1.44 mmol/L, P < .01), and
      absolute insulin levels were increased, but not to a significant extent. The
      rates of appearance (Ra) of exogenous and endogenous glucose were not modified,
      and the hypoglycemic effect of M in the postprandial state was entirely related
      to an increase in systemic glucose disposal (85.1 v 77.5 g/5 h, P < .001).
      Carbohydrate oxidation was unchanged, and glycolytic flux and nonoxidative
      glycolysis were increased by approximately 13 g/5 h (P < .01), with the excess
      lactate produced probably being converted to glycogen in the liver. Whole-body
      glycogen synthesis through the direct pathway tended to be reduced (-8 g/5 h, P >
      .05). Thus, M decreases postprandial glycemia by increasing glucose disposal and
      stimulates lactate production. The data also suggest that the drug increases the
      proportions of glycogen deposited through the indirect rather than the direct
      pathway.

PMID- 9030835
TI  - Accidental radiation injury to the hand: anatomical and physiological
      considerations.
AB  - A case study describing an accident in Mexico caused by failure to de-energize an
      x-ray spectrometer prior to repair is presented. The evolution, medical
      management, and outcome of the radiation injury to the hand are briefly reviewed.
      A discussion follows, with radiation injury and thermal burns compared and
      contrasted. The anatomy and physiology of thick skin and the vascular system of
      the hand are reviewed so that the reader will have a better understanding of the
      role of vascular injury in the pathological process that leads to tissue atrophy
      and radiation necrosis. Hyperbaric oxygen therapy, sympathectomy, and other
      techniques for improving circulation in involved areas are reviewed.

PMID- 9030836
TI  - Proposed model for estimating dose to inhabitants of 60Co contaminated buildings.
AB  - A model to predict the time weighted exposures to gamma radiation was developed
      for buildings constructed with structural steel having some contamination from
      60Co. Several buildings throughout sixteen city blocks in downtown Taipei were
      built about ten years ago with this material. These buildings were used for
      residential, business, and educational purposes with radiation levels ranging
      from background to five hundred times background. A comprehensive epidemiologic
      study by the National Yang Ming University Medical School in Taipei is underway
      to study the effects of this exposure to the building occupants. An evaluation of
      external radiation exposure was performed using survey instruments and
      thermoluminescent dosimeters. Exposure data from the survey instruments were used
      in a computer model developed to calculate cumulative radiation exposure
      estimates for the epidemiologic research. While the survey instrument data
      provided radiation levels at a point in time, the thermoluminescent dosimeters
      were placed in fixed locations and on several volunteers for a period of one
      month to verify the modeling results. The model itself is a mathematical
      algorithm that provides estimates with minimum and maximum range values by taking
      into account differences in the survey data between adults and children, variable
      occupancy patterns, background radiation, and radioactive decay. Several
      assumptions (background rates, height adjustment values, and occupancy factors)
      are easily adjusted to improve the estimated radiation exposures. The model
      predicted the exposures as measured by the thermoluminescent dosimeters with
      greater reliability for adults than for children. The differences between the two
      methods were about 10-15% for the adults and about 60% for the child. This
      strategy, its advantages, limitations, and its performance against actual
      thermoluminescent dosimeter measurements are presented.

PMID- 9030837
TI  - Dose equivalents to neutron therapy facility staff due to induced activation.
AB  - The sources of the induced activity from the d(48.5)+Be fast neutron therapy beam
      of the Harper Hospital superconducting cyclotron have been investigated. The
      distribution of activity in the treatment room was measured, and the levels of
      dose equivalent to the staff were established. Activation spectra were measured
      with a high purity RE-Ge detector. Peaks corresponding to 28Al, 56Mn, 24Na, 64Cu,
      66Cu, and 187W were present in the spectra. The dose equivalents due to the
      induced activation were measured by means of an ionization chamber type survey
      meter at six locations in the room. Irradiations of 120 monitor units were given
      at 15-min intervals, thus simulating the clinical situation. The measurements
      were made between the irradiations. The highest levels were registered around the
      treatment head. Two patterns are clearly distinguishable in these measurements. A
      fast decaying component with approximately 2 min half-life can be ascribed
      predominantly to 28Al and a slow growing component reaching saturation after
      about 4-5 treatments is associated with the presence of 56Mn. For uniform
      treatment load the activation build-up in each location was similar every day of
      the week with minimal values measured after the week end shut down. Personnel
      monitoring is achieved with dosimeters capable of detecting an extended range of
      neutron energies as well as beta rays and photons. Correlation between the number
      of fields treated and the doses to the radiation therapy technologists was shown.
      The mean dose equivalent received by the therapists is 7.1 +/- 0.2 microSv per
      treatment field. Means of reducing personnel dose equivalent levels are proposed.

PMID- 9030838
TI  - A statistical analysis of the internal organ weights of normal Japanese people.
AB  - Correlation of weights of various organs with age, body weight, and/or body
      height was statistically analyzed using data on the Japanese physique collected
      by the Medico-Legal Society from Universities and Research Institutes in almost
      all areas of Japan. After exclusion of unsuitable individual data for statistical
      analysis, findings for 4,667 Japanese, aged 0-95 y, including 3,023 males and
      1,644 females were used in the present study. Analyses of age-dependent changes
      in weights of the brain, heart, lung, kidney, spleen, pancreas, thymus, thyroid
      gland and adrenal gland and also of correlations between organ weights and body
      height, weight, or surface area were carried out. It was concluded that organ
      weights in the growing generation (under 19 y) generally increased with a
      coefficient expressed as (body height x body weight0.5). Because clear age
      dependent changes were not observed in adults over 20 y, they were classified
      into 4 physical types, thin, standard, plump and obese, and the relations of
      organ weights with these physical types were assessed. Some organs were
      relatively heavier in fat groups and light in thin individuals, or vice versa.

PMID- 9030839
TI  - Concentrations of 137Cs and 40K in edible mushrooms collected in Japan and
      radiation dose due to their consumption.
AB  - To estimate radiocesium intake due to eating mushrooms, about 100 samples
      belonging to 11 species were analyzed to establish representative values for
      137Cs and 40K in common edible mushrooms available in food markets. Concentration
      ranges were <0.047-39 Bq kg(-1) (wet wt) for 137Cs and 30-210 Bq kg(-1) (wet wt)
      for 40K. The median concentrations were 1.3 Bq kg(-1) (wet wt) for 137Cs and 97
      Bq kg(-1) (wet wt) for 40K. The 137Cs concentrations in cultivated mushrooms were
      markedly lower than those in wild mushrooms. The annual intake of 137Cs per
      person through mushrooms was calculated (using analytical results and food
      consumption data in Japan) to be 6.0 Bq for 137Cs, which is about 32% of the
      total dietary intake of this nuclide. The effective dose equivalent of 137Cs
      through mushroom was estimated to be 7.7 x 10(-8) Sv (range estimated from the
      standard deviation: 3.0 x 10(-8) - 2.0 x 10(-7)).

PMID- 9030840
TI  - Collective biodosimetry as a dosimetric "gold standard": a study of three
      radiation accidents.
AB  - Quantification of the biologically relevant dose is required for the
      establishment of cause-and-effect between radiation detriment or burden and
      important biological outcomes. Most epidemiological studies of unanticipated
      radiation exposure fail to establish cause and effect because of an inability to
      construct a valid quantification of dose for the exposed population. No one
      biodosimetric technique (biophysical or biological) meets all the requirements of
      an ideal dosimeter and thus qualify as a "gold standard." This report combines
      new results with previously published data in order to establish a collective
      biodosimetry as a dosimetric "gold standard" for the victims of three radiation
      accidents. Combining new and previously published data is necessary as execution
      and planning of a comprehensive dosimetry is rarely done at the initial stages of
      a radiation accident. The first subject was a fireman during the initial moments
      of the Chernobyl nuclear accident; the second was the victim of an unspecified
      occupational accident; and the third was exposed to a 60Co sterilization source.
      There was generally good agreement among the various biodosimetric techniques
      used for the three accident victims.

PMID- 9030841
TI  - Ambient air sampling for tritium--determination of breakthrough volumes and
      collection efficiencies for silica gel adsorbent.
AB  - Ambient air samples for tritium (as HTO) can be collected using the solid
      adsorbent silica gel. The purpose of this study was to determine the maximum
      practical sampling volume and overall collection efficiency for water vapor
      collected on silica gel columns and to demonstrate the use of an impinger-based
      system to load water vapor onto silica gel columns. Breakthrough volumes (Vb)
      were measured and chromatographic efficiencies (expressed as the number of
      theoretical plates, N) were calculated for a 20 degrees C to 50 degrees C
      temperature range, with the relative humidity at approximately 30%. The tests
      yielded relative breakthrough volumes (air volume/adsorbent depth, m3 cm(-1)) of
      0.36 for 20 degrees C, 0.20 for 30 degrees C, 0.15 for 40 degrees C, and 0.077
      for 50 degrees C. For 18-cm columns, the average tritium tracer recoveries at 20
      degrees C were 71% with no observed breakthrough for air volumes up to 5 m3,
      while at 40 degrees C mean tritium tracer recoveries dropped from 75% for volumes
      < or = 3.0 m3, to 0% for a volume of 5.0 m3. Frontal chromatographic profiles
      were measured for water vapor migrating through silica gel columns that were
      divided into 5 segments. The chromatographic efficiency of the silica gel columns
      was determined by graphical evaluation of the chromatography profiles. At a
      sampling rate of 0.25 L min(-1) and 30% relative humidity, the number of
      theoretical plates per adsorbent depth were 0.55 N cm(-1) at 20 degrees C, 0.68 N
      cm(-1) at 30 degrees C, 0.51 N cm(-1) at 40 degrees C, and 0.30 N cm(-1) at 50
      degrees C. Chromatographic theory was used to estimate the overall collection
      efficiency of the silica gel columns as a function of the ratio of the sampling
      volume to breakthrough volume and the chromatographic efficiency. For a 9.5 m3
      sample volume, 30% relative humidity, 0.25 L min(-1) sampling rate, and a 54-cm
      column, the overall collection efficiency was above 99.9% at 20 degrees C, above
      95% at 30 degrees C, just below 80% at 40 degrees C, and <<80% at 50 degrees C.

PMID- 9030842
TI  - Electrophysiological considerations relevant to the limiting of pulsed electric
      and magnetic fields.
AB  - The objective of the study was to theoretically examine the stimulation threshold
      of large myelinated axons and to use the results to formulate criteria for
      exposure limits of pulsed magnetic fields. The induced electric fields were
      calculated with a homogeneous tissue equivalent prolate spheroid. The stimulation
      level of the field was computed with the SENN model by using a folded axon with 2
      mm separation for the Ranvier nodes. In the case of rectangular induced electric
      field pulses, the asymptotic stimulation level for electric field strength was 10
      Vm(-1) with pulse durations greater than 100 micro(s) and for integrated electric
      field strength 1 x 10(-3) V m(-1)s with pulse durations less than 100 micro(s).
      The latter threshold level was exceeded in the surface of the prolate spheroid
      when the magnetic flux density changed by more than 7.4 mT within 100 micro(s).
      For sinusoidal bursts, the threshold amplitude of the magnetic field decreased
      asymptotically to a minimum value 2.5 mT when the carrier frequency and burst
      duration exceeded 5 kHz and 100 micro(s), respectively. If the same safety
      criteria are applied for pulsed and continuous exposure, the peak limits for
      induced current densities and magnetic field can exceed the amplitude values of
      the limits for continuous exposure only by a factor varying from 3 to 10.

PMID- 9030843
TI  - Solubility characterization of airborne uranium from an in situ uranium
      processing plant.
AB  - Solubility profiles of uranium dusts in the Irigaray uranium processing plant
      were determined by performing in vitro solubility tests on breathing zone air
      samples conducted in all process areas of the processing plant. The dissolution
      rate of the uranium on the air samples was then determined over the next 28 d in
      a simulant solution of the extracellular airway lining fluid (Gamble's solution).
      Airborne uranium in the wet process areas of the processing plant was highly
      soluble, with 97% dissolving in a 0.3 d half-time and 3% with a half-time of 15.6
      d. The airborne uranium dusts in the drum load out area were also soluble, with
      97% dissolving with a T1/2 of 0.25 d and the remainder with a T1/2 of 20 d.
      Exhaust from the drier stack and areas of the processing plant that had only this
      airborne uranium was slightly more insoluble, with 46% dissolving with a T1/2 of
      0.4 d and 53% with an 18 d half-time. These results compare well with x-ray
      diffraction analysis of the uranium samples and the bioassay program for the
      processing plant workers.

PMID- 9030844
TI  - Calibration of a portable tritium-in-air monitor for various radioactive gases.
AB  - A commercially available portable tritium-in-air monitor was calibrated for
      detecting the concentration of tritium-in-air, 14C-in-air, and various
      radioactive noble gases. Calibrations were performed both experimentally, using
      assayed quantities of the calibration gases, and theoretically, by simulating the
      monitor's response using Monte Carlo code. The experimental and theoretical
      calibrations agreed within +/- 10% for all gases tested with the exception of
      41Ar-in-air where the agreement was approximately 20%. The results show that,
      although the monitor can be used to measure a wide range of radioactive gases, if
      more than one gas is present the monitor can not be used to accurately determine
      the concentration of, and hazard posed by, these gases. It is also shown that the
      monitor's ability to accurately assess tritium-in-air hazards would be seriously
      compromised by the presence of other radioactive gases.

PMID- 9030845
TI  - Radiocesium body burdens in residents of northern Canada from 1963-1990.
AB  - Measurements of 137Cs body burdens in over 1,100 people from five northern
      Canadian communities were carried out with a portable whole body counting system
      during the winters of 1989 and 1990. These results are compared with over 3,000
      similar measurements carried out during 1967-1969. Community mean body burdens
      and body concentrations had decreased by approximately a factor of 30 between the
      two survey periods. The dependence of body concentrations on the sex and age of
      the subjects has also changed significantly. This can be related to changes in
      the patterns of caribou consumption in the northern communities. Measurements of
      137Cs in urine are also available for an earlier period (1963-1966) when world
      wide fallout was at its highest level. A normalization procedure was developed to
      calculate the average radiocesium body concentration in each community from the
      concentrations in urine. From data spanning a period of nearly 30 y (1963-1990),
      lifetime radiation doses have been estimated for most communities in the Yukon
      and Northwest Territories. These cumulative doses vary from 0.3 to nearly 40 mSv,
      with an Arctic-wide average of about 12 mSv. No health effects would be expected
      at these levels.

PMID- 9030846
TI  - A modified bottle manikin phantom for in vivo neutron activation analysis.
AB  - An artificial skeleton was designed and placed inside a bottle manikin absorber
      phantom to provide a new reference standard for measurements of total body
      calcium by in vivo neutron activation analysis at Brookhaven National Laboratory.
      The composition of the epoxy-based calcium and phosphorus mixture used to
      construct the skeleton, the dimensions and weight of each bone are given for two
      phantoms representing an adult male and female. Also, the dimensions,
      composition, and weights of overlays designed to simulate the influence of
      obesity on in vivo neutron activation analysis are given for each.

PMID- 9030847
TI  - Setting standards for radiation protection: the process appraised.
AB  - Present radiation protection standards are based to a large extent on data that
      have been forced to conform with the linear non-threshold model. A review of the
      literature shows that there are examples of both data and theory that disagree
      with such a model. Established standard setting bodies seem not to have
      recognized this disagreement; indeed, as will be shown, there are many studies
      that they have neither cited, discussed, nor refuted. Additionally, examples of
      data adaptation and circular reasoning are to be found in the standard-setting
      process. Consequently, a new approach to the process is desirable. Numerous
      citations and quotations are given.

PMID- 9030848
TI  - Detection limits for samples that give rise to counting data with extra-Poisson
      variance.
AB  - Detection limits are presented for duplicate background samples that produced
      counting data with extra-Poisson variance that was attributed to a nonuniform
      activity distribution in the background sample medium. The presence of extra
      Poisson variance was detected using the chi-squared test, where the presumed
      change in baseline activity from sample to sample was interpreted as an increase
      in experimental population variance. The runs test and Wilk-Shapiro test
      verified, respectively, the acceptable randomness of the data and the hypothesis
      that the data are normally distributed. Confidence intervals for detection limits
      therefore were based on the normal and t-distributions. The reduced chi-squared
      statistic was incorporated into the equations for the critical level and lower
      limit of detection to account for experimental variance beyond the expected
      Poisson value. The incorporation of extra-Poisson variance increased these
      detection limits for a well-defined background by a factor of 2.3 compared to the
      expected values for the paired-sample method which were derived under the
      assumption of Poisson variance, where the 30 background measurements have a
      reduced chi-squared statistic of 9.44.

PMID- 9030849
TI  - Examination of the effect of counting geometry on 125I monitoring using MCNP.
AB  - This paper theoretically investigates how the counting efficiencies of three
      selected detector (NaI) sizes are affected by neck-detector distance, detector
      misplacement, thickness of overlaying tissue, and size of the thyroid gland. The
      detector sizes were small, 2.54 cm diameter and 0.2 cm crystal thickness; medium,
      7.62 cm diameter and 0.2 cm crystal thickness; large 30.48 cm diameter and 0.2 cm
      crystal thickness. The evaluations were determined using a Monte Carlo technique.
      The simulations show that the large detector minimizes the uncertainties for all
      problems except the thickness of overlaying tissue.

PMID- 9030850
TI  - A proposed method to minimize waste from institutional radiation safety
      surveillance programs through the application of expected value statistics.
AB  - Institutional radiation safety programs routinely use wipe test sampling and
      liquid scintillation counting analysis to indicate the presence of removable
      radioactive contamination. Significant volumes of liquid waste can be generated
      by such surveillance activities, and the subsequent disposal of these materials
      can sometimes be difficult and costly. In settings where large numbers of
      negative results are regularly obtained, the limited grouping of samples for
      analysis based on expected value statistical techniques is possible. To
      demonstrate the plausibility of the approach, single wipe samples exposed to
      varying amounts of contamination were analyzed concurrently with nine non
      contaminated samples. Although the sample grouping inevitably leads to increased
      quenching with liquid scintillation counting systems, the effect did not impact
      the ability to detect removable contamination in amounts well below recommended
      action levels. Opportunities to further improve this cost effective semi
      quantitative screening procedure are described, including improvements in sample
      collection procedures, enhancing sample-counting media contact through mixing and
      extending elution periods, increasing sample counting times, and adjusting
      institutional action levels.

PMID- 9030851
TI  - Hospital discharge policy in thyroid cancer patients treated with 131I: the
      effect of changing from fixed time to exposure rate threshold.
AB  - During 1981-1989, a total of 2,238 thyroid carcinoma patients were treated in
      limited accommodation in Iran with high-fixed ablation or therapeutic doses of
      131I . For the 308 patients admitted in 1989, the external body exposure rate was
      measured sequentially at 2-4 d post-dose administration. Based on the exposure
      rate of 6.98 C kg(-1) h(-1) (1.8 mR h(-1) at 1 m, cumulative percentages of
      patients ablated with 3.7 GBq of 131I (268/308) and discharged from the hospital
      at 2, 3, and 4 d post-dose administration were 75%, 87%, and 95%, respectively.
      Likewise, for the group treated with 5.55 GBq (31/308), the cumulative
      percentages of patients discharged by day 2, 3, and 4 were 30%, 68%, and 79%,
      respectively. In the former, the remaining 5% (13 patients) had the external
      exposure rate less than 6.98 C kg(-1) h(-1) at one meter, before day seven PDA.
      In the latter, only 2 patients were released after day seven, that is at day 10,
      with the exposure rate less than 1.8 mR/hr at one meter. One patient, from the
      second group, with extensive metastatic disease was discharged at day 14 PDA with
      the external exposure rate of 5.81 C kg(-1)h(-1)(1.5 mR/hr) at one meter. By
      applying the above exposure rate as the requirement for the patient discharge, we
      changed the policy for release of patients from arbitrary 1-wk hospitalization to
      the discharge at the point when exposure rate dropped below 6.98 C kg(-1)h(
      1)(1.8 mR h(-1)) at 1 m, which led to the significant (300%) increase in
      throughput of patients treated for thyroid carcinoma with 131I, within the same
      available space limitations.

PMID- 9030853
TI  - Some critical remarks on the use of sex-specific tissue weighting factors for
      effective dose equivalent calculations.

PMID- 9030852
TI  - A novel portable grab sampler for tritiated water vapor.
AB  - The purpose of this work was to evaluate the applicability of a recently
      developed portable high-throughput liquid-absorption air sampler for measuring
      tritiated water vapor concentrations in nuclear facilities. A procedure for
      sampling tritiated water with a portable high-throughput liquid-absorption air
      sampler and measuring its concentration in air was developed with the aid of a
      theoretical model. Tritium concentrations in the air of a heavy water reactor
      currently being decommissioned, derived from samples obtained with a portable
      high-throughput liquid-absorption air sampler, a bubbler, and a cold trap,
      yielded comparable results, suggesting the applicability of the portable high
      throughput liquid-absorption air sampler to tritium grab sampling.

PMID- 9030854
TI  - Radon study shows little correlation.

PMID- 9030855
TI  - Neutrophils and adjuvant arthritis.

PMID- 9030856
TI  - Autoantigens in Addison's disease and associated syndromes.

PMID- 9030857
TI  - A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency.
AB  - We present a boy with hyper-IgM syndrome with a previously not reported mutation
      in the CD40 ligand gene. He also had a concomitant natural killer (NK) cell
      deficiency. He had no CD56+ or CD16+ cells and no NK activity as determined in 4
      h chromium release cytotoxicity assay. After 5 days in culture with IL-2
      containing medium, however, his peripheral blood mononuclear cells lysed both NK
      sensitive and NK-resistant targets, showing that he had lymphokine-activated
      killer cell precursors in the circulation. Due to the associated neutropenia, he
      was treated with granulocyte colony-stimulating factor (G-CSF) and responded
      well. In the same period we observed a transient increase in the number of NK
      cells. Isolated NK cell deficiencies are extremely rare. We suggest that the
      defect in our patient is part of the hyper-IgM syndrome, probably representing
      the phenotype of the new mutation described. Thus, it is possible that both the
      neutropenia and the NK cell deficiency are due to lack of growth-promoting
      signals normally delivered by the CD40 ligand.

PMID- 9030858
TI  - Expression of Bruton's tyrosine kinase in B lymphoblastoid cell lines from X
      linked agammaglobulinaemia patients.
AB  - X-linked agammaglobulinaemia (XLA) is an immunodeficiency caused by mutations in
      Bruton's tyrosine kinase (Btk) and is characterized by an almost complete arrest
      of B cell development. We analysed expression of Btk in B lymphoblastoid cell
      lines (BLCL) derived from four unrelated XLA patients. In one patient, with a 3 x
      5 kb genomic deletion encompassing the first (untranslated) exon, mRNA levels and
      in vitro kinase activities were very low. The patient manifested a mild phenotype
      with a delayed onset of the disease. Another mutation, in which the intron 3
      donor splice site is lost, was also associated with very low mRNA levels and an
      absence of detectable Btk protein. Patients with this mutation showed extensive
      heterogeneity of the immunological phenotype. In the BLCL of a third patient,
      with an Arg288 substitution in the SH2 domain, the mutation did not appear to
      affect the expression level, nor to abrogate in vitro phosphorylation activity.
      In the BLCL of the fourth patient, with an Arg28 mutation in the PH domain,
      tyrosine kinase activity in BTK precipitates appeared to be decreased compared
      with control BLCL.

PMID- 9030860
TI  - Anti-neutrophil monoclonal antibody therapy inhibits the development of adjuvant
      arthritis.
AB  - The aim of this study was to determine the contribution of neutrophils to
      adjuvant arthritis (AA) by in vivo depletion of peripheral blood neutrophils.
      Specific anti-neutrophil MoAb, RP3 (10 mg), or a control antibody was given twice
      daily on days 8-11 after injection of Mycobacterium tuberculosis in inbred male
      Sprague-Dawley rats. RP3 treatment inhibited the neutrophil leukocytosis
      associated with AA (3.3 +/- 0.6 x 10(3)/mm3 versus 21.2 +/- 6.9 x 10(3)/mm3;
      P<0.001). On day 12, control animals exhibited severe arthritis as assessed by
      articular index (AI) (9.2 +/- 1.3), increase in paw volume (149.3 +/- 10.6%), and
      synovial fluid (SF) cell count (5.3 +/- 0.5 x 10(5)). RP3 treatment significantly
      reduced AI (1 +/- 0.1; P<0.001), paw volume (103.6 +/- 5.8%; P<0.001) and SF
      cells (0.6 +/- 0.1 x 10(5); P<0.001) without affecting cutaneous DTH (treated 0.6
      +/- 0.1 mm change in thickness, control 0.8 +/- 0.2 mm; NS). Additional
      experiments demonstrated that CD4+ cell depletion but not decomplementation
      inhibited AA development and synovial neutrophil accumulation. Depletion of
      circulating neutrophils prevented joint inflammation and synovial leucocyte
      influx in AA, suggesting a pivotal role for neutrophils in the effector phase of
      AA. Inhibition of neutrophil accumulation by CD4+ cell depletion and not by
      decomplementation suggests that neutrophil accumulation in AA is T cell
      dependent.

PMID- 9030859
TI  - Role of gammadelta T lymphocytes in the development of Behcet's disease.
AB  - Phenotypic and functional properties of gammadelta T cells, which play an
      important role in mucocutaneous immunity, were examined to elucidate whether
      immunological abnormality in Behcet's disease may be related to a specific T cell
      population. We found that CD45RA+ Vgamma9+ Vdelta2+ gammadelta T cells, which
      constitute a minor population of gammadelta T cells in healthy individuals, were
      increased in number in Behcet's disease irrespective of disease activity. This
      CD45RA+ subset of gammadelta T cells in the active, but not inactive, phase of
      this disease expressed IL-2Rbeta and HLA-DR, suggesting that they are activated
      in vivo in active Behcet's disease. In addition, the CD45RA+ gammadelta T cells
      produced extreme amounts of tumour necrosis factor and contained perforin
      granules. These data indicate that a phenotypically distinct subset of gammadelta
      T cells, CD45RA+ CD45RO- Vgamma9+ Vdelta2+, may contribute to immunological
      abnormalities which may lead to complexity of pathophysiology in Behcet's
      disease.

PMID- 9030861
TI  - Differential effects of sex hormones on autoantibody production and proteinuria
      in chronic graft-versus-host disease-induced experimental lupus nephritis.
AB  - In patients with systemic lupus erythematosus, the female-to-male ratio is as
      high as 10:1. Sex hormones are thought to play a role in this difference in
      susceptibility. In a previous study, we demonstrated a high susceptibility of
      female mice to the development of glomerulonephritis after induction of chronic
      graft-versus-host disease (GVHD), compared with male mice. In order to unravel
      further this gender-related difference (C57B1/10*DBA/2)F1 hybrid mice were either
      castrated or ovariectomized and treated with 17beta-ethinyloestradiol or
      testosterone-decanoate preceding the induction of chronic GVHD. Testosterone
      decanoate reduced significantly the development of albuminuria in females. In
      contrast, proteinuria of 17beta-ethinyloestradiol-treated female mice was in the
      same range as that of sham-operated mice. Autoantibody levels against glomerular
      basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by
      ELISA, were higher in 17beta-ethinyloestradiol-treated female mice than in all
      other groups. Immunofluorescence studies showed the presence of immunoglobulin
      and complement deposits in glomeruli of all animals, without significant
      differences between the experimental groups. Our findings confirm earlier
      observations, in that testosterone-decanoate is shown to be an inhibitory
      compound, whereas 17beta-ethinyloestradiol has stimulating properties in
      autoimmunity. Moreover, our results show for the first time differential hormonal
      effects on autoantibody levels and proteinuria in experimental lupus nephritis.

PMID- 9030862
TI  - A bias in the alphabeta T cell receptor variable region gene usage in Takayasu's
      arteritis.
AB  - Takayasu's arteritis (TA) is a chronic large vessel vasculitis with a
      predilection for the aortic arch and its branches. T lymphocytes may be important
      in the pathogenesis, as they have been found to infiltrate the vascular lesions.
      To elucidate further the role of T cells in the disease, we studied circulating
      CD4+ and CD8+ T cells, expression of the activation marker (HLA-DR), marker for
      naive (CD45RA) and primed (CD45RO) cells and the different variable alpha/beta
      (AV/BV) gene segments on them. The TCR AV/BV repertoire was studied using a panel
      of 15 T cell receptor (TCR) V-specific MoAbs by flow cytometry in 18 patients and
      23 age- and sex-matched controls. Patients had a higher percentage of AV12S1 (P <
      0.05), BV6S7 (P < 0.05) and BV9 (P < 0.001)-bearing CD4+ cells. Patients also had
      a higher frequency of expansions, i.e. of T cell populations with an abnormally
      high TCR AV/BV gene usage. In patients' CD4+ subset of cells, there were 22
      expansions out of 231 analyses (9.5%), whereas in controls, four were expanded
      out of 310 analyses (1%) (P < 0.001). For CD8+ cells, the frequency of expansions
      was 32 in 231 analyses (14%) in patients and nine out of 304 analyses in controls
      (3%) (P < 0.01). In addition, there was a correlation between CD4+ expansions and
      disease activity; nine out of 10 patients with active disease in comparison with
      two out of eight patients with inactive disease (P < 0.01) had an expansion. Some
      of the expanded populations in patients were phenotypically characterized and
      observed to be HLA-DR+, CD28+, CD45RA+ and CD45RO+, with a greater proportion
      being CD45RO+. Patients had a higher percentage of expression of HLA-DR on both
      CD4+ and CD8+ T cells (P < 0.01). The percentages of naive and primed CD4+ and
      CD8+ T cells, gammadelta+ T cells and natural killer cells were comparable to
      those in the control group.

PMID- 9030863
TI  - Human autoimmune anti-proteinase 3 scFv from a phage display library.
AB  - This is the first study describing recombinant human antibody fragments directed
      to the autoantigen proteinase 3 (PR3) from an immune B cell source. Detection of
      these autoantibodies has proven valid for the diagnosis and monitoring of
      Wegener's granulomatosis. The described antibody fragment (scFv) was isolated
      from a phage display library prepared from the IgG-positive splenic lymphocytes
      of a patient with systemic autoimmunity. The cloning strategy was designed to
      maintain the diversity of the antibody variable gene repertoire, and sequencing
      of several variable genes demonstrated that all major heavy and light chain
      families were represented. We found an over-representation of particular heavy
      chain variable domains in splenic lymphocytes which differ from the ones
      frequently found in peripheral blood lymphocytes. It was possible to obtain
      specific scFv to PR3 after a single round of selection and the binding could be
      inhibited by the patients' sera. Although the antibody fragments in the splenic
      repertoire were found to be highly mutated, it was interesting to find that the
      selected scFv showed only limited somatic mutation. Furthermore, we could
      demonstrate that the removal of the mutations had no effect on binding
      specificity.

PMID- 9030864
TI  - Induction of hypoglycaemia in Japanese encephalitis virus infection: the role of
      T lymphocytes.
AB  - We report here development of hypoglycaemia in the convalescent phase of Japanese
      encephalitis virus (JEV) infection in mice by the induction of antigen-specific
      Ly1- 2+ T cells in the spleen which mediate hypoglycaemia through the generation
      of soluble T cell hypoglycaemic factor (TCHF). The TCHF acted in a dose-dependent
      manner and was found to be trypsin-sensitive and thermolabile. It was purified on
      Superose-12 high performance liquid chromatography (HPLC) gel filtration column
      and purified protein migrated as a approximately 25-kD band on SDS-PAGE. The JEV
      induced hypoglycaemia coincided with an increased circulating glucagon level,
      without any alterations in blood insulin and growth hormone concentrations. These
      effects were mimicked by TCHF. These results indicate that JEV-primed T
      lymphocytes mediate hypoglycaemia through the production of a soluble
      hypoglycaemic factor.

PMID- 9030865
TI  - Selective depletion of rectal lamina propria rather than lymphoid aggregate CD4
      lymphocytes in HIV infection.
AB  - The goal of this study was to examine the changes in lymphocyte populations in
      rectal mucosa during HIV infection and to study their relationship to mucosal
      immunity and to systemic depletion of CD4 lymphocytes. Rectal biopsies from 58
      HIV-infected subjects and eight controls were studied. Frozen rectal tissue
      sections were stained with antibodies to CD4, CD3, CD8, and markers for
      macrophages. HIV-infected subjects were divided into early stage (no
      opportunistic infections) and AIDS groups. There was profound depletion of rectal
      lamina propria CD4 lymphocytes (16% and 6% of normal content in early and AIDS
      groups, respectively). However, lymphoid aggregate CD4 lymphocytes were far less
      severely depleted (69% and 40% of normal content, respectively). The extent of
      lymphoid aggregate CD4 lymphocyte depletion generally parallelled the CD4
      lymphocyte depletion in the blood. CD8 lymphocyte content in both the lamina
      propria and lymphoid aggregates usually were increased, particularly in early
      stage patients. Macrophage contents were usually normal in the HIV-infected
      groups. We conclude that rectal lamina propria and lymphoid aggregates are
      distinct compartments differing markedly in their CD4 lymphocyte content during
      HIV infection. In light of this and an increased number of apoptotic cells which
      were noted in rectal lamina propria in HIV-infected subjects, we hypothesize that
      intestinal lamina propria could be a site of rapid CD4 lymphocyte destruction
      during HIV infection.

PMID- 9030866
TI  - Mannoproteins of Cryptococcus neoformans induce proliferative response in human
      peripheral blood mononuclear cells (PBMC) and enhance HIV-1 replication.
AB  - To investigate the possible role of Cryptococcus neoformans var. neoformans in
      HIV disease progression, and to identify the responsible cryptococcal components,
      an in vitro cell culture model was set up to study the C. neoformans-induced
      enhancement of HIV replication in HIV-1-infected PBMC. Similar to whole C.
      neoformans, cell-wall membrane fraction and mannoproteins induced proliferation
      of PBMC and enhancement of lymphotropic HIV replication in HIV-infected PBMC,
      while galactoxylomannan did not. MoAbs capable of interfering with MHC class II
      mediated antigen presentation prevented the induction of cell proliferation by
      whole C. neoformans or cryptococcal mannoproteins. MoAb binding to adhesion
      molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function
      associated antigen-1 (LFA-1) also inhibited C. neoformans-induced cell
      proliferation. In addition, anti-MHC class II MoAb inhibited the enhancement of
      HIV replication by C. neoformans. The results suggest that: (i) C. neoformans may
      accelerate HIV disease progression by stimulation of HIV replication through MHC
      class II-mediated antigen presentation; and (ii) cryptococcal mannoprotein may be
      one of the responsible components. The ability to enhance HIV replication in PBMC
      in vitro is not unique for C. neoformans. However, this is the first report to
      study in detail a yeast-induced enhancement of HIV replication in PBMC.

PMID- 9030867
TI  - HIV infection of CD45RA+ and CD45RO+ CD4+ T cells.
AB  - HIV preferentially infects the RO+ memory subset of CD4+ lymphocytes, and these
      cells are lost earlier in HIV infection than their RA+ counterparts. Although
      both populations express similar amounts of CD4 and bind the HIV envelope
      glycoprotein (gp120) equally well, calcium signals and CD4 down-regulation
      subsequent to gp120 binding are not the same in both populations. Data suggest
      these disparities are mediated by differential tyrosine kinase (TK) regulation.
      Syncytium formation is enhanced in RO+ cells, partly a consequence of increased
      leucocyte function antigen-1 (LFA-1) expression and, again, partly due to altered
      TK regulation. After in vitro HIV infection, reverse transcription is not
      detected in RA+ cells, is minimal in the RO+ class II- population, but progresses
      well in RO+ class II+. Infection followed by mitogen stimulation permits reverse
      transcription in all cells. HIV infection of RO+ cells is enhanced moderately at
      multiple points in the virus life cycle.

PMID- 9030868
TI  - Diagnostic value of CD45RO expression on circulating T lymphocytes of fetuses and
      newborn infants with pre-, peri- or early post-natal infections.
AB  - We examined the expression of the CD45RO antigen, which characterizes the antigen
      primed/memory phenotype of T lymphocytes, as a marker for congenital infection in
      blood samples of newborns and fetuses. CD45RO expression on T cells was
      determined by triple-colour fluorescence flow cytometry. In total 537 blood
      samples of newborns and infants up to an age of 3 months and 89 fetal blood
      samples from gestational weeks 19-31 were analysed. Of the newborns and infants,
      74 had a clinically, serologically and/or antigenically evident infection, and
      four of the fetuses had a confirmed intra-uterine infection. In 35 infants with
      acute predominantly bacterial infections such as sepsis or pneumonia, 17 (48.6%)
      had elevated CD45RO(bright) expression. In 39 infants with proven pre-, peri- or
      early post-natal infections with toxoplasmosis, cytomegalovirus (CMV), rubella,
      herpes simplex virus (HSV) or human herpes virus type 6 (HHV6), 25 (64.1%)
      exhibited enhanced CD45RO(bright) expression. Three of four fetuses with
      confirmed intra-uterine infection (three with CMV, one with parvovirus B19)
      exhibited elevated CD45RO(bright) expression. The specificity of the CD45RO assay
      for detecting microbial infections was 94.6% for newborns and infants up to 3
      months and 90.6% for fetuses. It is concluded that elevated numbers of
      CD45RO(bright) T cells in infants up to 3 months of age strongly suggest an
      infection. However, the sensitivity of the CD45RO assay is not sufficient to
      enable the test to be used as a general marker for prescreening infants to detect
      pre-, peri- or early post-natally acquired infections.

PMID- 9030869
TI  - High frequency of Epstein-Barr virus (EBV) lymphoblastoid cell line-reactive
      lymphocytes in cord blood: evaluation of cytolytic activity and IL-2 production.
AB  - We investigated natural immunity towards autologous EBV lymphoblastoid cell lines
      (EBV-LCL) in the cord blood. Cord blood lymphocytes (CBL) from 20 healthy
      neonates were examined together with three EBV+ and one EBV- adult donors. We
      found that high frequencies of EBV-LCL-reactive cytotoxic lymphocytes, ranging
      from 1/190 to 1/12,205 were detectable in EBV- and EBV+ donors, as well as in the
      cord blood of 15 out of 20 neonates. Surface phenotype analysis, depletion
      experiments with MoAbs specific for T and natural killer (NK) lymphocyte subsets,
      and T lymphocyte cloning procedures strongly indicate virus-specific cytotoxic T
      lymphocytes (CTL) as the major population responsible for the lysis of autologous
      EBV-LCL in EBV+ donors. Conversely, a high frequency of NK cells seems to be
      involved in the killing activity observed in neonates and in the EBV- donor.
      Frequencies of EBV-LCL-induced IL-2-producing lymphocytes were high in EBV+
      donors (range 1/2247-1/6633) and heterogeneous, but consistent, in cord blood
      (range 1/5072-1/57,819) and in the EBV- adult (1/17,148). CD8+ lymphocytes were
      responsible for IL-2 production in EBV+ individuals, while CD4+ T cells were
      charged with this role in cord blood and in the EBV- donor. These data
      demonstrate that CBL are able to develop a strong innate immunity, directed
      against autologous EBV-infected cells, mediated by both NK cells and CD4+ T
      lymphocytes. This characteristic may be relevant for protection against viral
      infections in both neonates and patients given cord blood transplantation (CBT).

PMID- 9030870
TI  - Wild isolates of Plasmodium falciparum malaria show decreased sensitivity to in
      vitro inhibition of parasite growth mediated by autologous host antibodies.
AB  - Antigenic diversity in field populations of Plasmodium falciparum parasites may
      delay the acquisition of protective immunity to malaria, the development of which
      may thus require repeated exposure to infection over a prolonged period of time.
      In this study we show that P. falciparum parasites may vary in their sensitivity
      to antibody-mediated invasion/growth inhibition in vitro. Wild isolates of P.
      falciparum from children living in an endemic area of Burkina Faso were tested
      for their sensitivity to the growth inhibitory effects of antibodies originating
      from the same (autologous) and from other donors (heterologous). A significantly
      lower invasion inhibition activity was obtained when the isolates and antibodies
      were tested in autologous compared with heterologous combinations. The lower
      sensitivity to growth inhibition by autologous antibodies may be due to immune
      pressure in vivo, selecting from a heterogeneous parasite population those with a
      low expression of the antigens recognized by the host's antibodies.
      Alternatively, the parasites cultured from each child might represent expanding
      parasite populations, mainly constituting strains not earlier seen by the immune
      system of that specific host. The results reinforce the concern about Plasmodium
      antigenic diversity as a major obstacle towards the development of an effective
      malaria vaccine.

PMID- 9030871
TI  - Different Trypanosoma cruzi strains promote neuromyopathic damage mediated by
      distinct T lymphocyte subsets.
AB  - The proliferative response of CD4 and CD8 T lymphocytes obtained from C3H/HeN
      mice chronically infected with Trypanosoma cruzi strains that differ in
      virulence, tropism and immunogenicity, was assayed against skeletal muscle,
      sciatic nerve and spinal cord homogenates. Although both CD4 and CD8 T
      lymphocytes from mice infected with the RA strain strongly proliferated against
      the nervous system, no response against skeletal muscle antigens was detected.
      CD4 and CD8 T lymphocytes from mice infected with the K-98 clone (from CA-I
      strain) showed low proliferative response against all the antigens assayed. To
      determine whether the proliferation patterns showed correlation with T cell
      mediated neuromuscular damage, passive cell transfer studies were performed.
      Fifteen days after transfer of CD4 T cells from RA-infected donors (CD4-RA),
      normal syngeneic recipients displayed exclusively nervous tissue damage, such as
      perineural, endoneural and/or meningeal inflammatory infiltrates, with
      predominance of CD4 T cells. Fifteen days after transfer of CD4 T lymphocytes
      from mice infected with K-98 (CD4-K98), recipients showed inflammatory
      infiltrates only in skeletal muscle, where CD4 T lymphocytes and macrophages were
      predominant cells. Recipients of CD8 T cells from RA-infected mice (CD8-RA)
      showed lesions in both spinal cord and sciatic nerves. Higher percentages of CD8
      T cells were observed in comparison with the recipients of CD4-RA or CD4-K98. In
      contrast, CD8 T cells from K-98-infected donors (CD8-K98) did not induce tissue
      damage. These results provide evidence that mice infected with T. cruzi
      populations that differ in their biological characteristics show diverse immune
      mechanisms that may be involved in the pathogenesis of peripheral nervous system
      damage.

PMID- 9030872
TI  - Immunoprecipitation of steroidogenic enzyme autoantigens with autoimmune
      polyglandular syndrome type I (APS I) sera; further evidence for independent
      humoral immunity to P450c17 and P450c21.
AB  - Three steroidogenic P450 cytochromes, steroid 17alpha-hydroxylase (P450c17),
      steroid 21-hydroxylase (P450c21) and side-chain cleavage enzyme (P450scc), have
      been described as autoantigens in APS I. In this study we report an
      immunoprecipitation assay for the detection of autoantibodies to these three
      enzymes using in vitro 35S-labelled antigens. Overall, 33 out of 46 (72%)
      patients with APS I had autoantibodies to at least one of the three proteins and
      each protein was recognized by patient sera with equal frequency. A higher rate
      of autoantibody positivity was observed in APS I patients with Addison's disease
      compared with patients without Addison's disease (85% versus 39%). All 11
      patients with ovarian failure had anti-P450c17 or anti-P450scc antibodies. The
      immunoprecipitation results with P450c17, P450c21 and P450scc correlated well
      with the results obtained by immunoblotting assays. In addition, the
      steroidogenic enzymes 11beta-hydroxylase (P450c11beta), aromatase (P450arom),
      3beta-hydroxysteroid dehydrogenase (3betaHSD) and adrenodoxin were studied by
      immunoprecipitation assay, but no reaction was found either with 46 APS I or with
      26 healthy control sera. To study the suggested immunological cross-reactivity
      between P450c17 and P450c21 enzymes, nine APS I patient sera were preabsorbed
      with bacterially expressed P450c17 or P450c21 and subsequently used in
      immunoprecipitation assay. The absorption experiments clearly indicated that the
      preincubation inhibited only the reactivity of corresponding antigen, suggesting
      independent autoantibody response to the two enzymes. Our results suggest that
      the immune response to some but not to all steroidogenic enzymes is a specific
      feature of APS I that may be pathogenically significant.

PMID- 9030873
TI  - 21-hydroxylase autoantibodies in adult patients with endocrine autoimmune
      diseases are highly specific for Addison's disease. Belgian Diabetes Registry.
AB  - The diagnostic specificity of recombinant 21-hydroxylase autoantibodies (21OH-Ab)
      for Addison's disease was tested in adult patients with either Graves' disease
      (GD), insulin-dependent diabetes mellitus (IDDM), or polyendocrinopathy, as well
      as in healthy controls. Using a radiobinding assay with in vitro translated
      recombinant human 21-hydroxylase, we found 21OH-Ab in 24/28 (86%) idiopathic
      Addison patients, and using an immunofluorescence assay we found adrenal cortex
      autoantibodies (ACA) in 12/28 (43%) patients (P = 0.002). All the 12 ACA-positive
      sera were also positive for 21OH-Ab and ACA were found in 11/15 (73%) patients
      with less than 15 years and in 1/13 (8%) patients with 15-38 years of disease
      duration (P = 0.002). 21OH-Ab were present in 3/92 (3%) patients with GD, in
      1/180 (0.6%) with IDDM and in 0/106 healthy subjects. The 21OH-Ab-positive GD and
      IDDM patients were also positive for ACA. None of 17 patients with
      polyendocrinopathy, but without Addison's disease, had 21OH-Ab. None of the 180
      Belgian IDDM patients had Addison' s disease or developed an adrenal
      insufficiency at follow up. In two out of three Graves patients, the presence of
      21OH-Ab was associated with clinical and biochemical signs of adrenal
      insufficiency. Of the 89 21OH-Ab-negative patients with GD none had Addison's
      disease at the time of blood sampling, and 79 were followed up for 5.6-7.5 years
      and none developed clinical signs of adrenal insufficiency. We conclude that the
      presence of 21OH-Ab in patients with endocrine autoimmune diseases is highly
      specific for Addison's disease.

PMID- 9030874
TI  - Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult
      periodontitis.
AB  - Capture ELISAs with biotinylated monospecific antibodies were developed to detect
      both C-reactive protein (CRP) and haptoglobin (Hp) in serum of adult
      periodontitis (AP) patients and normal subjects. Each acute-phase reactant was
      significantly increased in serum from AP patients with CRP at 9.12 +/- 1.61 mg/l
      versus 2.17 +/- 0.41 mg/l (P < 0.001) and Hp at 3.68 +/- 0.37 g/l versus 1.12 +/-
      0.78 g/l (P < 0.001). Assessment of clinical characteristics of the patients'
      periodontal disease indicated that CRP and Hp levels were significantly increased
      in patients with the most frequent disease active episodes (P < 0.02 and P <
      0.001, respectively). Longitudinal examination of the Hp levels showed a
      significant decrease following scaling and root planing (3.68 versus 2.38 g/l; P
      < 0.01). After a 2-year administration of 50 mg/b.i.d. Flurbiprofen (a non
      steroidal anti-inflammatory drug), significantly decreased Hp levels were noted
      (P < 0.005). CRP levels declined by 35-40% after 1-2 years of treatment with the
      drug (P < 0.05). The findings indicated that localized infections resulting in
      increased inflammation and tissue loss in the periodontium elicit systemic host
      changes manifest by increases in two acute-phase reactants. The conclusions are
      that either these molecules are formed locally and distributed to the serum, or
      these presumably localized infections impact upon the systemic components of the
      host protective responses.

PMID- 9030875
TI  - Neutralization of tumour necrosis factor (TNF) but not of IL-1 reduces
      inflammation in chronic dextran sulphate sodium-induced colitis in mice.
AB  - The cytokines TNF and IL-1 have been implicated as mediators of the inflammatory
      processes in patients with inflammatory bowel disease (IBD). To investigate the
      role of these cytokines in mucosal inflammation we used anti-cytokine strategies
      in a mouse model of acute and chronic colitis. Mice which received 5% dextran
      sulphate sodium (DSS) in their drinking water showed signs of acute colitis on
      day 4, with severe weight loss and bloody diarrhoea. Chronic colitis was
      established after four cycles of feeding 5% DSS for 7 days and water for 10 days,
      with the mice showing diarrhoea but no weight loss. In acute colitis, treatment
      with anti-IL-1 reagents, anti-TNF MoAb, or dexamethasone (DEX) led to
      aggravation. By contrast, in chronic colitis, treatment of mice with several IL-1
      activity-inhibiting reagents failed to show significant effects, whereas anti-TNF
      MoAb or DEX significantly reduced the colitis. We conclude that in acute colitis
      IL-1 and TNF are beneficial, whereas in chronic colitis, TNF but not IL-1 seems
      to play a major role in perpetuation of chronic inflammation.

PMID- 9030876
TI  - Effects of interferon-alpha (IFN-alpha) administration on leucocytes in healthy
      humans.
AB  - Plasma concentrations of IFN-alpha are increased in several inflammatory
      conditions. Several lines of evidence indicate that IFN-alpha has anti
      inflammatory properties. To study the effects of IFN-alpha on leucocyte subsets
      and activation and on cytokines, we administered IFN-alpha (rhIFN-alpha2b; 5 x
      10(6) U/m2) to eight healthy human subjects in a randomized controlled cross-over
      study and analysed changes in circulating leucocytes and parameters for
      neutrophil and monocyte activation. After administration of IFN-alpha, neutrophil
      counts increased, monocyte counts decreased transiently, whereas the number of
      lymphocytes, basophils and eosinophils showed a sustained decrease. IFN-alpha
      administration was also associated with neutrophil activation, reflected in an
      increase in the plasma concentrations of elastase-alpha1-antitrypsin complexes
      and lactoferrin. Serum neopterin, a marker for monocyte activation, was
      significantly increased 10 h after administration of IFN-alpha. IFN-alpha
      significantly increased plasma concentrations of IL-6, IL-8 and IL-10. Although
      IL-1 and tumour necrosis factor (TNF) remained undetectable, plasma
      concentrations of soluble TNF receptors p55 and p75 increased after IFN-alpha
      administration. We conclude that IFN-alpha induces multiple alterations in the
      distribution and functional properties of leucocytes. IFN-alpha exerts pro- as
      well as anti-inflammatory effects within the cytokine network.

PMID- 9030877
TI  - Tumour cell killing using chemically engineered antibody constructs specific for
      tumour cells and the complement inhibitor CD59.
AB  - Immunotherapy using MoAbs is inefficient due to limited activation of human
      effectors by mouse antibodies and multiple protective mechanisms available to
      host cells against autologous complement. We have used chemically engineered
      antibody constructs and human complement in vitro to specifically target and kill
      neoplastic B lymphoid cells (Raji). Fab'gamma Fc gamma2 chimaeric antibody
      (specific for human CD37) was used to activate the classical pathway of human
      complement on Raji cells, whilst CD59 was neutralized using one of two different
      bispecific F(ab'gamma)2 antibody constructs which contained both cell-targeting
      (anti-CD19 or anti-CD38) and CD59-neutralizing moieties. When either bispecific
      construct was used to neutralize CD59, 15-25% of cells were lysed. If CD55 was
      also neutralized using specific antibody, Raji cells were efficiently killed (70%
      lysis). When added to a mixture of target (Raji) and bystander (K562) cells, one
      bispecific antibody (anti-CD38 x anti-CD59) could be specifically delivered to
      Raji, avoiding significant uptake on CD59-expressing bystander cells (K562). The
      second bispecific antibody (anti-CD19 x anti-CD59) bound equally well to either
      cell type. Cell-specific targeting was dependent upon combination of a low
      affinity anti-CD59 Fab'gamma with a high-affinity anti-tumour cell Fab'gamma.
      When Raji and K562 cells were mixed and incubated with a combination of the
      engineered constructs and anti-CD55 antibodies, Raji cell lysis (30-40%) was
      observed in the absence of K562 killing. We propose that combinations of these
      constructs may be of use for treatments such as ex vivo purging of autologous
      bone marrow or in vivo targeting of tumour cells.

PMID- 9030878
TI  - Analysis of rearranged immunoglobulin heavy chain variable region genes obtained
      from a bone marrow transplant (BMT) recipient.
AB  - Haematopoietic stem cell transplantation has been used for the treatment of many
      different malignant and non-malignant diseases. The immune system of transplant
      recipients must be regenerated from the transplant inoculum, and it is not
      surprising that many transplant recipients are deficient in generating specific
      antibody responses to exogenous stimuli. This B cell immunodeficiency in these
      patients is associated with clinically significant infections, although the
      underlying mechanism remains unknown. We have previously shown that the pattern
      of usage of V(H) genes was similar between healthy subjects and BMT recipients,
      indicating that the immunodeficiency was not due to a dramatic imbalance in V(H)
      utilization. However, motif-specific hybridization analysis indicated that the
      accumulation of somatic mutations was much greater among rearrangements in
      controls than in BMT recipients. The failure of BMT recipients to accumulate
      somatic mutations in rearranged V(H) genes correlates with an absence of IgD- B
      cells, and is consistent with a defect in antigen-driven B cell responses. In the
      current study, which extends those findings, we have determined the nucleotide
      sequences of 68 heavy chain rearrangements from one patient as well as 39
      rearrangements from a healthy control. Analysis of these sequences made possible
      a more precise definition of variable region configuration and of the status of
      somatic mutation in this BMT recipient. The results validate the hybridization
      data and support the conclusion that, although somatic hypermutation and, by
      inference, antigen-driven responses are detected in BMT recipients, they are
      deficient compared with healthy subjects as late as 1 year after transplant.

PMID- 9030879
TI  - Identification and characterization of cells infiltrating the graft and aqueous
      humour in rat corneal allograft rejection.
AB  - In a rat model of corneal transplantation, Fischer 344 (RT1(lv1)) rats received
      orthotopic corneal isografts or Wistar-Furth (RT1(u)) donor allografts. Rejection
      was observed in 25 of 26 allograft recipients, at a median time of 18 days, with
      all isografts surviving > 100 days. Flow cytometric analysis of aqueous humour
      identified cellular infiltration of the aqueous at the time of allograft
      rejection, in contrast to the acellular aqueous found in isografts at
      corresponding times following transplantation. A higher proportion of CD8+ than
      CD4+ cells was found at days 1-3 following rejection, whereas there was a higher
      proportion of CD4+ cells at days 5-8. No changes in peripheral blood T cell
      subsets were found at the time of rejection. Immunohistochemical analysis of
      cells infiltrating recipient iris and grafted cornea undertaken at days 1-2, 4
      and 7-10 following onset of rejection, demonstrated inflammatory cells in the
      graft epithelium, stroma and aggregated on the endothelium. Large numbers of
      macrophages, T cells (CD4+ > CD8+ at all time points), natural killer (NK) cells
      and neutrophils were detected in graft tissue at days 1-2 and 4, diminishing
      after that time. Most infiltrating cells expressed MHC class II antigen, and a
      smaller number expressed IL-2R. Expression of the co-stimulatory marker B7 was
      identified in a few cells at day 4 in the region of the graft-host wound. The
      immune response in graft rejection was characterized at day 4 also by expression
      of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells of iris and
      corneal vessels, demonstration of interferon-gamma on mononuclear cells in the
      peripheral (recipient) cornea, and tumour necrosis factor-alpha on aggregated
      mononuclear cells on the graft, but not recipient, endothelium. Only sparse
      cellular infiltrates were found in isograft controls, with inflammation located
      at the graft-host wound. These findings suggest that inflammatory cells reach a
      corneal allograft by two routes--from vessels in the peripheral recipient cornea,
      and from vessels in the recipient iris via the aqueous humour. Different aqueous
      and intragraft T cell subset proportions were seen early in rejection, although a
      preponderance of CD4+ cells was found in both aqueous and graft at later times.

PMID- 9030880
TI  - Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in response
      to Staphylococcus aureus and staphylococcal superantigen in childhood atopic
      dermatitis.
AB  - We have examined the cell-mediated immunity (CMI) to Staphylococcus aureus (S.
      aureus) and Staphylococcal enterotoxin B (SEB) in peripheral blood mononuclear
      cells (PBMC) from children with atopic dermatitis (AD) and from non-atopic child
      controls by measurement of proliferative responses and production of the
      cytokines IFN-gamma and IL-4. PBMC from children with AD showed significantly
      higher proliferative responses to both S. aureus (P < 0.01) and SEB (P < 0.05).
      Despite this enhanced proliferation, production of IFN-gamma in response to S.
      aureus (P < 0.001) and SEB (P < 0.01) from these PBMC was significantly
      diminished. In contrast, PBMC from children with AD were significantly more
      likely to produce IL-4 in response to S. aureus (P < 0.01). These findings
      demonstrate in vitro heightened CMI to S. aureus in children with AD, and
      implicate S. aureus as a potent inflammatory stimulant. Impaired IFN-gamma
      production to S. aureus in vivo may result in failure to eradicate S. aureus from
      skin. The organism's persistence on skin would contribute to inflammation by
      causing continued T cell activation and release of pro-inflammatory mediators.

PMID- 9030881
TI  - The 80-kD fibronectin fragment increases the production of fibronectin and tumour
      necrosis factor-alpha (TNF-alpha) in cultured mesangial cells.
AB  - The presence of fibronectin (FN) fragments has been demonstrated in several
      inflammatory processes, and they have been implicated in the recruitment of
      mononuclear cells. However, the interaction of these FN fragments with resident
      cells has hardly been studied. We have hypothesized that the 80-kD FN fragment,
      which includes the RGD cell binding domain of FN, could contribute to the
      pathogenesis of glomerular damage through the interaction with mesangial cells
      (MC) via alpha5beta1 integrin. Since an increase in the glomerular deposit of
      matrix components, particularly FN, is frequently observed in progressive
      glomerulonephritis, we studied whether its synthesis is modulated by the 80-kD FN
      fragment and the native FN molecule. While the 80-kD FN fragment stimulated FN in
      a dose-dependent manner, both at the mRNA and protein level, the whole FN
      molecule exerted a dual effect. High doses produced FN inhibition, while low
      doses elicited a certain increase. This stimulation was abrogated by the presence
      of Sam-1, a MoAb against the alpha-subunit of the alpha5beta1 integrin. Since
      cytokines play a fundamental role in glomerular injury, we studied the production
      of TNF-alpha, one of the most powerful mediators of inflammation. TNF-alpha
      synthesis was induced by the 80-kD FN fragment, in a dose-dependent manner, but
      not by native FN. When MC were incubated with the 29- and 31-kD FN fragments,
      which lack the RGD cell binding domain, TNF-alpha secretion was not detected.
      These results strongly suggest that in cultured MC, the 80-kD FN fragment induces
      the synthesis of matrix proteins such as FN, and cytokines such as TNF-alpha, via
      alpha5beta1 integrin. This mechanism could contribute to the perpetuation of
      renal injury.

PMID- 9030882
TI  - Proinflammatory cytokines regulate Fc alphaR expression by human mesangial cells
      in vitro.
AB  - IgA nephropathy (IgAN) is defined by the predominant deposition of IgA immune
      complexes (IC) in the glomerular mesangium. Interaction between IgA immune
      complexes and mesangial cells (MC) could be a linchpin for the genesis of IgAN.
      We studied the modulation of MC expression of IgA receptors (Fc alphaR) by
      selected cytokines. Binding of 125I-IgA to quiescent human MC showed 2.55 x 10(5)
      sites/cell with an affinity (Ka) of 3.2 x 10(7) M(-1). Addition of selected
      recombinant cytokines had no significant influence on Ka, but increased the
      number of sites/cell relative to unstimulated cells. Northern hybridization using
      the pHuFc alphaR cDNA probe showed time-dependent increases in mRNA expression in
      stimulated versus control cells. IL-6 and tumour necrosis factor-alpha (TNF
      alpha) had a biphasic effect on the Fc alphaR mRNA level; at 48 h, IL-6 increased
      steady state mRNA levels about six-fold relative to control, TNF-alpha increased
      mRNA four-fold, and interferon-gamma (IFN-gamma) induced Fc alphaR mRNA two-fold.
      By reverse transcriptase-polymerase chain reaction (RT-PCR), the Fc alphaR
      expressed on human MC appears highly homologous to that expressed by U937 cells.
      Altered Fc alphaR expression in response to cytokines may influence the
      pathogenesis of IgAN by affecting deposition and/or clearance of IgA-IC in the
      mesangium.

PMID- 9030883
TI  - Phenotypic characterization of T cells in bronchoalveolar lavage fluid (BALF) and
      peripheral blood of patients with diffuse panbronchiolitis; the importance of
      cytotoxic T cells.
AB  - We investigated the contribution of T cells in diffuse panbronchiolitis (DPB) by
      identifying T cell subsets in BALF of 36 patients with DPB, before and after long
      term treatment with macrolide antibiotics, and 16 healthy control subjects. The
      percentages of lymphocytes and CD3+ gammadelta+ cells in BALF of DPB patients and
      control subjects were similar, but the absolute number of these cells was higher
      in DPB patients. Treatment resulted in a significant reduction in the absolute
      number of these cells. A further two-colour analysis of T cell subsets in BALF
      showed a significantly higher ratio and number of CD8+ HLA-DR+ cells in DPB
      patients. Treatment resulted in a significant reduction of activated T cells.
      Most BALF CD8+ cells were CD8+ CD11b- cytotoxic T cells. The number of these
      cells in BALF of DPB patients (26.69 +/- 5.86 x 10(3)/ml) was higher than the
      control (2.02 +/- 0.38 x 10(3)/ml; P < 0.001), and a significant reduction was
      observed after treatment (7.69 +/- 2.59 x 10(3)/ml; P < 0.01). The number of CD4+
      cells was also higher in DPB patients than in controls, and most were CD4+ CD29+
      memory T cells. However, treatment did not influence the number of these cells.
      The number of lymphocytes, CD3+ gammadelta+, CD8+ CD11b-, CD8+ HLA-DR+, and CD4+
      CD29+ cells was higher in patients with bacterial infection than in those without
      bacterial infection, and interestingly, macrolide therapy reduced the number of
      lymphocytes, CD3+ gammadelta+, CD8+ CD11b- and CD8+ HLA-DR+ cells, irrespective
      of bacterial infection. In peripheral blood, the percentage of CD8+ HLA-DR+ cells
      was also higher in DPB patients than in healthy subjects, and significantly
      decreased after treatment. The percentage of CD8+ CD11b- cells in peripheral
      blood was similar in DPB patients and normal subjects, and treatment
      significantly reduced the percentage of these cells. Finally, the expression of
      the adhesion molecules CD11a/CD18 (alpha/beta-chains of LFA-1) on lung CD3+ cells
      and CD49d (alpha-chain of VLA) on lung CD4+ cells was enhanced compared with that
      on peripheral blood in DPB patients. Our results suggest that elevation of memory
      T cells and activation of CD8+ cells, mainly cytotoxic T cells, in the airway
      lumen of DPB patients may contribute to chronic bronchial inflammation, possibly
      through up-regulation of adhesion molecules. Our findings also indicate that
      macrolide antibiotics may have a direct or indirect suppressive effect on
      cytotoxic T cells, and as such, reduce inflammation and improve clinical
      condition.

PMID- 9030884
TI  - Radiation damage and immune suppression in splenic mononuclear cell populations.
AB  - We have examined alterations in all of the major splenic mononuclear cell (SMNC)
      populations in C57B1/6 mice following whole-body irradiation (0-700 cGy) in order
      to determine which populations may play a role in active immune suppression
      and/or haematopoietic recovery. A protocol has been established for
      characterization and differentiation by flow cytometric analysis (FCA) of the
      major MNC populations in the mouse spleen: T lymphocytes (CD4+ and CD8+ cells), B
      lymphocytes, natural killer (NK) cells, and monocytes/macrophages. Ionizing
      radiation caused decreased spleen cellularity and decreased ability of surviving
      SMNC to respond to mitogen. FCA revealed alterations in the relative composition
      of the constituent splenic cell populations following irradiation, reflecting
      differential radiosensitivity, with selective enrichment of NK cells (seven-fold)
      and CD4+ T lymphocytes (three-fold). Enrichment developed during the 7-day post
      irradiation period. In addition, some MNC became activated in a dose- and time
      dependent fashion following whole-body irradiation, as indicated by expression of
      CD71, the transferrin receptor. These cells were CD34+ and Thy 1.2+, but were CD4
      or CD8- as well as CD45- (B cell). The observed increase in NK cells corresponds
      with a previously reported increase in natural suppressor (NS) cells following
      total-lymphoid irradiation (TLI). The balance of recovery-inhibiting NK cells and
      recovery-enhancing CD4+ T lymphocytes following irradiation may reflect or
      influence the degree of haematopoietic recovery, and may provide an indication of
      the extent of damage (biological dosimetry).

PMID- 9030885
TI  - Serum amyloid A gene expression in rabbit, mink and mouse.
AB  - The expression of serum amyloid A (SAA) protein, a major acute-phase reactant in
      most species, was examined by in situ hybridization in multiple organs of rabbit,
      mink and mouse. In livers of unstimulated mice and rabbits a heterogeneous
      pattern of SAA expression in hepatocytes was observed. In all three species,
      lipopolysaccharide (LPS) administration resulted in extensive uniform
      hybridization of SAA probes to hepatocytes and in the rabbit SAA transcripts were
      detected in cells in the white pulp of the spleen, the adrenal cortex and ovary
      as well as in the mucosa and lymphatic vessels of the small intestine.
      Examination of hybridizing SAA signals in the rabbit myocardium showed a speckled
      distribution in myocytes. The rabbit endocardium was strongly positive, and in
      the kidney rabbit SAA mRNA was mainly confined to epithelial cells of the
      proximal and distal convoluted tubules. In the unstimulated mouse, SAA mRNA was
      detected in the liver and epithelial cells of the small and large intestine.
      After stimulation of an acute-phase response with LPS a strong response was seen
      in these organs as well as in the convoluted tubules of the kidney. In
      extrahepatic organs of the mink, no SAA mRNA was detectable in unstimulated
      animals, while the convoluted tubules of the kidney and uterine endometrium were
      strongly positive after systemic LPS injection.

PMID- 9030886
TI  - Synthesis of guanidinosuccinate from argininosuccinate and reactive oxygen in
      vitro.
AB  - Synthesis of guanidinosuccinic acid (GSA), a uremic toxin, has been suggested to
      relate to the urea concentration and synthetic rate. Among the urea cycle
      enzymes, inhibition of argininosuccinate (ASA) lyase by urea has been reported.
      Argininosuccinate which contains a GSA structure is a candidate of a GSA
      precursor. We found that another uremic toxin, methylguanidine, is formed from
      creatinine with reactive oxygen species. Therefore, we investigated in vitro
      whether GSA is formed from ASA with reactive oxygen species. GSA was measured by
      HPLC by a post-column-labeling method using 9,10-phenathrequinone. When 1 mmol/l
      ASA was reacted with the hydroxyl radical-generating system for 5 min at pH 7.4,
      9 mumol/l GSA was formed. Dimethylsulfoxide, a hydroxyl radical scavenger,
      markedly inhibited GSA synthesis. The superoxide radical generated by xanthine
      and xanthine oxidase reaction also formed 1 mumol/l GSA from 1 mumol/l ASA and
      the GSA formation was inhibited by superoxide dismutase or catalase almost
      completely. Addition of FeCl2 to the xanthine/xanthine oxidase reaction further
      increased GSA synthesis. These results indicate that GSA is formed from ASA by
      reaction with the hydroxyl radical and the superoxide radical.

PMID- 9030887
TI  - Role of reactive oxygen and argininosuccinate in guanidinosuccinate synthesis in
      isolated rat hepatocytes.
AB  - The synthesis of guanidinosuccinic acid (GSA) increases in uremics, and GSA is
      implicated as a uremic toxin. The GSA synthesis increases roughly in proportion
      to the serum urea level that increases in patients with renal failure. Urea is a
      specific inhibitor of argininosuccinase, the fourth urea cycle enzyme, and might
      lead to the increase of argininosuccinate (ASA). We found that GSA is formed from
      ASA by reactive oxygen species in vitro. In this paper, we investigated GSA
      synthesis from ASA in isolated rat hepatocytes and the effect of reactive oxygen
      species on this synthesis. When isolated rat hepatocytes were incubated with 5
      mmol/l ASA, GSA was formed linearly with time up to 6 h (16 nmol/g wet liver/6
      h). GSA was formed depending on the ASA concentration up to 10 mmol/l.
      Dimethylsulfoxide, a hydroxyl radical scavenger, inhibited GSA synthesis by 65%.
      GSA was actively formed when the hepatocytes were incubated with 32 mmol/l urea.
      The GSA formation in the presence of urea was also inhibited by
      dimethylsulfoxide, although the inhibition was less marked. FeCl2, that increases
      the hydroxyl radical generation, increased GSA synthesis. These results indicate
      that GSA is formed from ASA in isolated hepatocytes. The results also suggest
      that reactive oxygen species are important for GSA synthesis in the cells.

PMID- 9030888
TI  - Isozymes of superoxide dismutase from Aloe vera.
AB  - Extracts from the parenchymatous leaf gel and the rind of the Aloe vera plant
      (Aloe barbadensis Miller) were shown to contain seven electrophoretically
      identifiable superoxide dismutases (SODs). The chromatographic elution profiles
      and the migration of these bands on native polyacrylamide gel electrophoresis
      (PAGE), for both the gel and rind, are quite similar. Two of these seven
      activities are insensitive to cyanide treatment, suggesting that they are mangano
      SODs. The other five activities are sensitive to cyanide treatment, but
      insensitive to azide treatment and are presumed to be cupro-zinc SODs. All of the
      seven proteins appear to be homodimers with apparent native molecular masses
      centered at approximately 32 and 42 kD as indicated by SDS-PAGE and gel
      filtration (FPLC) chromatography. The specific activities of SODs in the A. vera
      rind and gel are comparable to those of spinach leaves and of rabbit liver.

PMID- 9030889
TI  - Relationship between adipose polyamine concentrations and triacylglycerol
      synthetic enzymes in lean and obese Zucker rats.
AB  - Previous studies from our laboratory demonstrate that polyamines, namely spermine
      and spermidine, stimulate adipose triacylglycerol formation from the sn-glycerol
      3-phosphate pathway by activation of several enzymes from this pathway, including
      sn-glycerol-3-phosphate acyltransferase, Mg(2+)-dependent phosphatidate
      phosphohydrolase and diacylglycerol acyltransferase. Since obesity in Zucker rats
      was associated with increased accumulation of adipocyte triacylglycerols, we have
      examined the relationship between changes in the activities of various
      triacylglycerol synthetic enzymes and the endogenous concentrations of spermine
      and spermidine in the adipose tissues from lean and obese animals. As compared
      with lean rats, the adipocytes from obese rats showed a 4-fold rise in the
      concentration of spermine and spermidine which was accompanied by 4- to 14-fold
      increases in the activities of various triacylglycerol synthetic enzymes,
      including Mg(2+)-dependent phosphatidate phosphohydrolase. These studies suggest
      that obesity in Zucker rats is associated with the activation of various adipose
      triacylglycerol synthetic enzymes resulting from increased concentrations of
      endogenous spermine and spermidine.

PMID- 9030890
TI  - In vitro aggregation facilities beta-amyloid peptide-(25-35)-induced amnesia in
      the rat.
AB  - The beta-amyloid peptide-(25-35) fragment, but not beta-amyloid peptide-(1-28),
      shares with beta-amyloid protein-(1-42) the ability to self-aggregate and to
      induce neurotoxicity in vitro. This study examined the induction of amnesia in
      rats given intracerebroventricularly soluble or aggregated beta-amyloid peptide
      (25-35) (5-45 nmol), or beta-amyloid peptide-(1-28) (15 nmol). Memory deficit in
      the water-maze test, examined 14 days after aggregated beta-amyloid peptide-(25
      35) injection, was more pronounced than with soluble beta-amyloid peptide-(25
      35). beta-Amyloid peptide-(1-28) only affected retention. These results confirm
      the direct amnesic properties of beta-amyloid peptides in the rat brain and
      showed that prior peptide aggregation markedly facilitates the appearance of
      amnesia.

PMID- 9030891
TI  - Conditional control by midazolam and amphetamine in a rapid appetitive
      discrimination procedure.
AB  - The present two experiments examined conditional control by midazolam and
      amphetamine cues in an appetitive discrimination procedure. In each of two
      experiments, male Wistar rats were subjected to a small number of two types of
      training sessions in a conditioning box. During one type of session, a stimulus
      was consistently followed by food in a magazine, whereas during the other type of
      session, this very same stimulus was followed by nothing. Groups of rats were
      injected with either midazolam (0.1 mg/kg, s.c.) or amphetamine (0.5 mg/kg,
      s.c.), prior to each food-reinforced session, and with saline prior to each food
      non-reinforced session. Other groups received the reverse treatment. Subsequent
      non-reinforced test session showed that, in both experiments, only the rats that
      had been food reinforced in a drug state displayed shorter magazine-response
      latencies in their previously reinforced than in their previously non-reinforced
      state, both prior to and during the stimulus. This finding was interpreted as
      reflecting the joint operation of unconditioned and conditioned drug effects,
      with the latter being based on occasion setting by the drug cues that was induced
      by the relatively short discrimination training procedure. The present results
      parallel those of previous aversive drug-discrimination experiments adopting a
      similar short discrimination procedure.

PMID- 9030892
TI  - Enzyme-catalyzed production of the neuroprotective NMDA receptor antagonist 7
      chlorokynurenic acid in the rat brain in vivo.
AB  - NMDA receptors play a critical role in neurotransmission and are also involved in
      the occurrence of excitotoxic nerve cell death. Synthetic halogenated analogs of
      the endogenous broad spectrum excitatory amino acid receptor blocker kynurenic
      acid are among the most potent and selective antagonists of the glycine co
      agonist site of the NMDA receptor complex. Pharmacological blockade of this site
      provides neuroprotection in animal models of cerebral ischemia, epilepsy and
      neurodegenerative disorders, and does not appear to be associated with some of
      the undesirable side effects linked to classic competitive and non-competitive
      NMDA receptor antagonists. Here we demonstrate the neuroprotective quantities of
      7-chloro-kynurenic acid (7-Cl-KYNA), one of the most selective and well-studied
      glycine site antagonists, can be synthesized in the brain from its bioprecursor L
      4-chlorokynurenine (4-Cl-KYN). Intracerebral infusion of 4-Cl-KYN dose
      dependently reduced quinolinate neurotoxicity in the rat hippocampus after
      enzymatic conversion to 7-Cl-KYNA by kynurenine aminotransferase. In accordance
      with previous studies demonstrating that kynurenine aminotransferase is
      preferentially localized in astrocytes, both the enzymatic formation of 7-Cl-KYNA
      and the neuroprotective potency of 4-Cl-KYN were substantially reduced following
      an intrahippocampal injection of the gliotoxin fluorocitrate. In situ produced 7
      Cl-KYNA offers a novel neuroprotective strategy for targeting the glycine/NMDA
      site while avoiding excessive receptor blockade and reducing the clinical risks
      associated with conventional NMDA receptor antagonism.

PMID- 9030893
TI  - Hippocampal and cerebellar extracellular amino acids during pilocarpine-induced
      seizures in freely moving rats.
AB  - Limbic seizures were provoked in freely moving rats by intrahippocampal
      administration of the muscarinic receptor agonist pilocarpine via a microdialysis
      probe (10 mM for 40 min at 2 microliters/min). Changes in extracellular
      hippocampal and cerebellar glutamate, aspartate and gamma-aminobutyric acid
      (GABA) levels were monitored during and after pilocarpine administration. Effects
      of systemic or local administration of anticonvulsants on the seizures and
      concomitant changes in amino-acid concentrations, were investigated. Pilocarpine
      induced seizures were completely abolished after intraperitoneal premedication
      for 7 days with phenobarbital (15 mg/kg per day) and after intrahippocampal
      administration of 10 mM phenobarbital and 1 mM carbamazepine (180 min at 2
      microliters/min). Rats premedicated with carbamazepine (5 mg/kg per day) still
      developed seizures. The changes in extracellular hippocampal amino-acid levels
      suggest that glutamate, aspartate and GABA are not involved in seizure onset, but
      may play a role in seizure maintenance and/or spread in the pilocarpine animal
      model of epilepsy. The increases in extracellular amino acids in ipsi- and
      contralateral cerebellum following limbic seizures provoked in the hippocampus,
      probably play a role in the 'reversed' diaschisis phenomenon.

PMID- 9030894
TI  - Extracellular aspartate concentration increases in nucleus accumbens after
      cocaine sensitization.
AB  - Rats were sensitized to cocaine (15 mg/kg, i.p.) by 6 daily injections followed
      by a 48 h withdrawal prior to cocaine challenge. Involvement of excitatory amino
      acids in behavioral sensitization was assessed by comparing extracellular levels
      of aspartate and glutamate in the core of the nucleus accumbens in response to
      the first cocaine injection and the final cocaine challenge. Intracerebral
      microdialysis of the nucleus accumbens in freely moving awake rats allowed the
      comparison of behavioral state with extracellular aspartate and glutamate
      concentrations. Increased nucleus accumbens extracellular concentration of
      aspartate, but not glutamate, was observed in rats exhibiting behavioral
      sensitization to cocaine.

PMID- 9030895
TI  - Endothelium- and cytochrome P-450-dependent relaxation induced by isoproterenol
      in rat aortic rings.
AB  - In rat aortic rings, the mechanism of endothelium-dependent relaxation induced by
      isoproterenol is examined. Pretreatment with (+/-)-1-[2,3]-(dihydro-7-methyl-1H
      inden-4-yl)oxy]-3-[(1-methyleth yl)amino] -2-butanol (ICI-118,551), a beta 2
      adrenoceptor antagonist, or atenolol, a beta 1-adrenoceptor antagonist, partly
      inhibited the relaxing response to isoproterenol. The relaxing response to
      isoproterenol in the presence of ICI-118,551 or atenolol was markedly inhibited
      by removal of endothelium. In the aorta pretreated with ICI-118,551 or atenolol,
      residual relaxing response to isoproterenol was also inhibited by 2-methyl-1,2-di
      3-pyridyl-1-propanone (metyrapone), alpha-naphthoflavone or 8-methoxypsoralen,
      cytochrome P-450 monoxygenase inhibitors, and methylene blue, but not by
      indomethacin, a cyclooxygenase inhibitor, 2,3,5-trimethyl-6-(12-hydroxy-5,10
      dodecadiynyl)-1, 4-benzoquinone (AA861), a 5-lipoxygenase inhibitor, NG-nitro-L
      arginine (NOARG), a nitric oxide synthase inhibitor, Zn protoporphyrin IX, a heme
      oxygenase inhibitor, or yohimbine, a alpha 2-adrenoceptor antagonist. In the
      aorta denuded of endothelium, metyrapone did not affect the residual relaxing
      response to isoproterenol in the presence of atenolol. These results suggest that
      the cytochrome P-450 system may be involved in the endothelium-dependent
      relaxation induced by isoproterenol through beta 1- and beta 2-adrenoceptor
      activation.

PMID- 9030896
TI  - GW1229, a novel neuropeptide Y Y1 receptor antagonist, inhibits the
      vasoconstrictor effect on neuropeptide Y in the hamster microcirculation.
AB  - We studied the effect of GW1229, a novel neuropeptide Y Y1 receptor antagonists,
      on the vasoconstriction induced by neuropeptide Y and structurally related
      analogs in the hamster cheek pouch microcirculation. Changes in arteriolar
      diameter and microvascular conductance were assessed by intravital microscopy and
      measurement of sodium22 clearance. GW1229 did not affect basal vascular
      conductance but inhibited, concentration dependently, the reduction in arteriolar
      diameter and vascular conductance induced by 100 nM neuropeptide Y. GW1229 also
      counteracted the vasoconstrictor effect of 100 nM [Leu31,Pro34]neuropeptide Y,
      and that of 300 nM neuropeptide Y-[(13-36). In contrast, GW1229 had no effect on
      the vasoconstriction induced by noradrenaline. We conclude that the
      vasoconstrictor effect on neuropeptide Y in the hamster cheek pouch is mediated
      by neuropeptide Y Y1 receptors. The maintenance of physiological tone in this
      vascular bed does not involve the participation of endogenous neuropeptide Y.

PMID- 9030897
TI  - The effect of Cu2+ on rat pulmonary arterial rings.
AB  - In the current study, Cu2+ was tested for its ability to relax vessels and to
      accumulate cyclic GMP (cGMP) in rat pulmonary artery employing rat extrapulmonary
      arterial rings. Cu(2+)-induced relaxation was endothelium and concentration (in
      the range from 10(-7) to 10(-4) M) dependent. The content of cGMP in the rings
      was increased 1.7-fold with 10(-4) M Cu2+. NG-Monomethyl-L-arginine abolished
      both the copper-induced relaxation and the increase in cGMP of rings. Cu2+ and
      zaprinast, which inhibits phosphodiesterase activity, caused a synergistic
      increase in cGMP level in the rings, suggesting that Cu2+ enhanced cGMP level
      through a mechanism different from that of zaprinast, probably as a consequence
      of elevated accumulation of nitric oxide (NO). The magnitude of vasorelaxation
      observed due to simultaneous addition of Cu2+ and acetylcholine was additive, not
      synergistic. Cu2+ did not augment relaxation induced by exogenously added NO
      donor. These results suggest that Cu2+ elevates NO level in the rings not by
      prolonging the half-life of NO, but by activation of endothelial nitric oxide
      synthase and subsequently potentiating the action of NO on vascular tone.

PMID- 9030899
TI  - Ameliorating effect of an endothelin ETA receptor antagonist on renal function of
      DOCA-salt hypertensive rats.
AB  - The effects of FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1 H-azepinyl)]
      carbonyl]amino-4-methyl-pentanoyl]amino-3[3-(1-methyl -1 H
      indolyl)]propionyl]amino-3-2(2-pyridyl)propionic acid), an endothelin ETA
      receptor antagonist, on renal hemodynamics and urine formation were examined
      using anesthetized deoxycorticosterone acetate (DOCA)-salt hypertensive rats, in
      which renal perfusion pressure was protected from FR139317-induced hypotension
      with an aortic clamp. An intravenous injection of FR139317 (10 mg/kg) to sham
      operated normotensive control rats produced no significant changes in renal
      hemodynamic and excretory responses. In DOCA-salt hypertensive rats, FR139317
      caused sustained renal vasodilation. Urine flow and urinary excretion of sodium
      were increased significantly following drug injection. We suggest that endothelin
      1 and the endothelin ETA receptor play an important role in water and sodium
      retention, and in renal vasoconstriction in this model of hypertension.

PMID- 9030898
TI  - Cromakalim blocks the purinergic response evoked in rat vas deferens by single
      pulse electrical stimulation.
AB  - The present study was carried out to look at the influence of the K+ channel
      opener cromakalim, compared with suramin and prazosin, on the contractile
      response evoked by single-pulse field stimulation and exogenous agonists in
      epididymal and prostatic portions of rat vas deferens. In the epididymal portion
      suramin abolished the first phase of the response to single shock, prazosin
      deeply affected the second phase and a combination of both antagonists almost
      completely abolished both phases. Cromakalim was able to inhibit in a
      concentration-dependent manner the first purinergic phase (pD2 = 5.90 +/- 0.11),
      leaving practically unaffected the second, adrenergic phase. This inhibitory
      effect of cromakalim on the electrically evoked response was counteracted by
      glibenclamide. Cromakalim and prazosin, but not suramin, affected the response to
      exogenous noradrenaline. Suramin but not cromakalim was able to antagonize
      responses to alpha, beta-methylene-ATP. In the prostatic portion because of a
      less clear discrimination between adrenergic and purinergic phases of the
      electrically evoked response, the picture was less clear although the trend was
      identical. Cromakalim was not able to antagonize the response to ATP. It is
      concluded that in rat vas deferens cromakalim inhibits purinergic transmission by
      acting prejunctionally.

PMID- 9030900
TI  - Adrenomedullin induces penile erection in the cat.
AB  - The present study was undertaken to investigate the effects of intracavernosal
      injections of adrenomedullin, a novel hypotensive peptide, on penile erection in
      anesthetized cats. Responses to adrenomedullin were compared to those elicited by
      intracavernosal injection of the control triple-drug combination (1.65 mg
      papaverine, 25 micrograms phentolamine, and 0.5 microgram prostaglandin E1).
      Intracavernosal injections of adrenomedullin in doses of 0.1-1.0 nmol elicited
      dose-related increases in cavernosal pressure and penile length. The maximal
      effect of adrenomedullin injection on cavernosal pressure was an 8-fold increase
      in pressure, which was 74% of that induced by the triple-drug combination. The
      maximal effect on penile length was a 43% increase when compared to baseline
      value, which was comparable to that induced by the triple-drug combination. The
      duration of the peak pressure and total duration of the peptide effect were
      significantly shorter in response to the 1 nmol dose of adrenomedullin than was
      observed with the control triple-drug combination. Intracavernous injection of
      the control triple-drug combination resulted in a significantly greater decrease
      in systemic arterial blood pressure than did adrenomedullin. Erectile responses
      to adrenomedullin were not altered following administration of the nitric oxide
      synthase inhibitor. N omega-nitro-L-arginine, at a time when erectile responses
      to acetylcholine were significantly reduced. These data demonstrate that
      intracavernous injection of adrenomedullin induces a short-lived erection in cats
      that is not due to the release of nitric oxide.

PMID- 9030902
TI  - Modulation of the inflammatory response by corticotropin-releasing factor.
AB  - Peptides of the corticotropin-releasing factor (CRF) family have been shown to
      have either pro- or anti-inflammatory activities. CRF (10-30 micrograms/kg)
      administered subcutaneously or intravenously could inhibit edema and dye leakage
      in the rat paw produced by several injuries. These findings are opposed to some
      results suggesting a predominantly pro-inflammatory effect of CRF mainly in
      arthritic processes. The purpose of this work was to identify in vivo and in
      vitro the conditions for the pro- or anti-inflammatory actions of CRF in order to
      clarify its physiological and pharmacological function. Using the rat paw edema
      test we observed that only the highest doses of CRF employed (5 micrograms)
      induced a moderate and sustained swelling. Pre-treatment with low doses of CRF
      (0.5-5 ng) was able to inhibit the edema induced by Naja naja phospholipase A2,
      carrageenin or histamine. Higher doses (50 ng-5 micrograms) had no anti
      inflammatory activity. When co-inhibited with Naja naja phospholipase A2 or
      histamine the peptide did not modify the swelling at doses up to 500 ng, showing
      at 5 micrograms an additive edema with Naja naja phospholipase A2. In vitro, CRF
      did not modify the release of histamine but slightly increased the release of
      arachidonic acid to the medium. Our findings show a clear dose dependence on the
      local effects of CRF in inflammatory responses. These results suggest that the
      mechanisms of the two dose-related phenomena may be distinct.

PMID- 9030901
TI  - Blockade of angiotensin converting enzyme but not of angiotensin AT1 receptors
      improves glucose tolerance.
AB  - This study compared the effect of benazepril, an angiotensin converting enzyme
      inhibitor to valsartan, an angiotensin AT1 receptor antagonist, on glucose
      tolerance in the conscious, spontaneously hypertensive rat. Intraperitoneal
      infusion of benazepril or valsartan at 1, 3 and 10 mg/kg per day produced
      equivalent dose-related reductions in systolic blood pressure for 12 weeks. Body
      weight gain during the treatment period was significantly reduced by infusion
      rates of benazepril. In contrast, only the highest infusion rate of valsartan
      significantly affected body weight gain. At the end of the 12-week treatment
      period, neither benazepril nor valsartan significantly affected glucose disposal
      during intravenous glucose tolerance tests. The insulin response to glucose
      challenge was unaffected by valsartan whereas following the highest infusion rate
      of benazepril the plasma levels were significantly reduced. The results
      demonstrate that benazepril but not valsartan reduces the insulin required to
      dispose of a glucose load.

PMID- 9030903
TI  - High carbachol increases the electrically induced [Ca2+]i transient in the single
      isolated ventricular myocyte of rats.
AB  - In order to investigate the mechanisms responsible for the inotropic effects of
      muscarinic acetylcholine receptor stimulation by high concentrations of
      muscarinic receptor agonists, we studied the effects of carbachol at 30-300
      microM on the electrically induced [Ca2+]i transient of rat isolated ventricular
      myocytes. Carbachol at this dose range increased the amplitude and duration of
      the electrically induced [Ca2+]i transient time and dose dependently. It also
      increased the resting fluorescence ratio and time to 80% decline of amplitude
      from the peak. At 100-300 microM the increase in [Ca2+]i transient was followed
      by a cluster of Ca2+ oscillations in 50-83% of the cells studied. The effects
      were blocked by atropine, but not pertussis toxin. Depletion of Ca2+ from
      sarcoplasmic reticulum by ryanodine, which itself reduced the amplitude of the
      [Ca2+]i transient and increase resting fluorescence, abolished the effect of
      carbachol on the [Ca2+]i transient without affecting its effect on resting
      fluorescence ratio. The caffeine-induced [Ca2+]i transient was unaffected by
      prior addition of carbachol in a Ca2+ free and low Na+ solution. Inhibition of
      Ca2+ by the L-type Ca2+ channel blocker, verapamil, which itself reduced the
      amplitude of the [Ca2+]i transient without affecting the resting fluorescence
      ratio, attenuated the augmentation of the amplitude of the [Ca2+]i transient
      elicited by carbachol. Ni2+, a non-specific Ca2+ channel blocker and an inhibitor
      of Na(+)-Ca2+ exchange, abolished the effects of carbachol on both [Ca2+]i
      transient and resting fluorescence ratio. Low external Na+, which increased the
      resting fluorescence ratio due to its inhibitory effect on Na(+)-Ca2+ exchange,
      also abolished the effects of carbachol. The results indicate that the inotropic
      effect of muscarinic acetylcholine receptor stimulation by high concentrations of
      a muscarinic receptor agonist may be due to an increase in the electrically
      induced [Ca2+]i transient in ventricular myocytes via a process which is not
      pertussis toxin sensitive. The increase in the electrically induced [Ca2+]i
      transient may result from increases in Na2(+)-Ca2+ exchange and influx of Ca2+
      via voltage-gated Ca2+ channels, and mobilization of Ca2+ from the intracellular
      store. The mobilization of Ca2+ from the intracellular store is a secondary
      event. The study has provided for the first time that muscarinic acetylcholine
      receptor stimulation by high concentrations of carbachol increases Ca2+ influx
      via the Ca2+ channel and mobilization of Ca2+ from its intracellular store. The
      study has also demonstrated for the first time the occurrence of Ca2+
      oscillations induced by high concentrations of carbachol.

PMID- 9030904
TI  - Diltiazem derivatives modulate the dihydropyridine-binding to intact rat
      ventricular myocytes.
AB  - To examine whether the modulation of the 1,4-dihydropyridine-binding by diltiazem
      derivatives, which has been shown in cardiac and skeletal muscle membranes, takes
      place in intact cardiac myocytes, effects of diltiazem on the specific binding of
      [3H](+)-PN200-110 to freshly isolated adult rat ventricular myocytes were
      investigated in normal Tyrode solution at 37 degrees C. Diltiazem consistently
      potentiated the [3H](+)-PN200-110-binding in a concentration-dependent manner,
      while DTZ323 (3-(acetyloxy)-5-[2-[[2- (3,4-dimethoxyphenyl)ethyl]
      methylamino]ethyl]-2,3-dihydro-2(-4 methoxyphenyl)-1,5-benzothiazepin-4-(5H)
      one), a potent diltiazem derivative, inhibited it in a non-competitive manner. In
      saturation studies, 100 microM decreased the Kd value of the 3[H](+)-PN200-110
      binding (control, 0.102 +/- 0.008 vs. diltiazem, 0.074 +/- 0.004 (nM, n = 6), P <
      0.05) without significant effect on Bmax (control, 65.7 +/- 6.4 vs. diltiazem,
      76.7 +/- 4.4 (fmol/mg protein, n = 6). Moreover, membrane-impermeant quaternary
      diltiazem also potentiated the [3H](+)-PN200-110-binding in intact myocytes.
      These results suggest that diltiazem modulates the 1,4-dihydro-pyridine-binding
      even in intact cardiac myocytes, and the binding site of diltiazem is accessible
      from the extracellular side of the L-type Ca2+ channels.

PMID- 9030905
TI  - Determination of delta-opioid in NG108-15 cells.
AB  - The delta-opioid receptors in mouse neuroblastoma x rat glioma NG108-15 cells
      were characterized by receptor binding and cAMP assays. Saturation binding assays
      using [3H][D-Pen5]enkephalin (DPDPE) or [3H][D-Ser2, Leu5, Thr6]enkephalin
      (DSLET) gave similar binding capacities (Bmax). Competition binding assays showed
      that DPDPE and DSLET have similar affinity for the [3H]DPDPE or 3[H]DSLET binding
      sites. The rank order of potency of competition with [3H]DPDPE and [3H]DSLET was
      similar: naltriben approximately DSLET > or = DPDPE > 7-benzylidenenaltrexone
      (BNTX). Both DPDPE and DSLET were found to decrease cAMP formation. The action of
      DSLET was antagonized by naltriben but not BNTX, while the action of DPDPE was
      reversed by both antagonists. Therefore, the delta-opioid receptor in NG108-15
      cells has similar affinity for the agonists DPDPE and DSLET, and a higher
      affinity for the antagonist naltriben than BNTX.

PMID- 9030906
TI  - Tetrandrine inhibits electrically induced [Ca2+]i transient in the isolated
      single rat cardiomyocyte.
AB  - The effect of tetrandrine on the electrically induced elevation of cytosolic Ca2+
      concentration, [Ca2+]i, in the single isolated rat cardiomyocyte was studied with
      a fluorometric ratio method using fura-2 acetomethylester (fura-2/AM) was Ca2+
      indicator. Tetrandrine (3-100 microM) concentration and time dependently
      inhibited the amplitude of the [Ca2+]i transient without any significant effect
      on the resting level of [Ca2+]i. At high concentrations (60-100 microM),
      tetrandrine also prolonged the time to reach the peak (t1.0) and the time to
      decline the 20% of the peak level (t0.2) of the electrically induced [Ca2+]i
      transient. The effect of tetrandrine was fast in onset and fully reversible upon
      washout. Tetrandrine (10 microM) partially inhibited the elevation of [Ca2+]i in
      response to KCl-induced depolarization. Verapamil and diltiazem mimicked the
      effects of tetrandrine given at low concentrations, but not at high
      concentrations. At high concentrations, tetrandrine reduced the magnitude of the
      caffeine-induced [Ca2+]i transient. Tetrandrine (100 microM) administered after
      thapsigargin, which itself decreased the amplitude and prolonged the duration of
      the electrically induced [Ca2+]i transient, further decreased the amplitude of
      the [Ca2+]i elevation. After ryanodine, which itself decreased the amplitude of
      the [Ca2+]i transient, 100 microM tetrandrine not only further reduced the
      amplitude, but also prolonged the duration of the electrically induced [Ca2+]i
      transient. These results provide evidence that in addition to its inhibitory
      effect on Ca2+ influx at the sarcolemma at the therapeutically relevant
      concentrations, tetrandrine at high concentrations may inhibit Ca2+ uptake into
      the sarcoplasmic reticulum.

PMID- 9030907
TI  - Tacrine inhibits nicotinic secretory and current responses in adrenal chromaffin
      cells.
AB  - Tacrine enhanced acetylcholine-induced catecholamine secretion with a
      concentration of up to 10 microM, but inhibited it at over 10 microM in perfused
      adrenal glands. Qualitatively the same result was obtained with physostigmine.
      Both tacrine and physostigmine only inhibited the secretory responses to
      carbachol and/or nicotine in perfused glands and dispersed chromaffin cells.
      Acetylcholinesterase activity of adrenal homogenates was inhibited by tacrine and
      physostigmine in a concentration-dependent manner. In whole-cell patch-clamp
      experiments, tacrine and physostigmine caused reversible inhibition of nicotine
      evoked inward currents with a dose range similar to that for the inhibitory
      action on the secretory response. These results suggest that the enhancing effect
      of tacrine and physostigmine on acetylcholine-induced catecholamine secretion
      results from the prevention of enzymatic hydrolysis of acetylcholine in adrenal
      glands and that the inhibitory effect is due to the inhibition of nicotinic
      receptor-mediated membrane currents in adrenal chromaffin cells.

PMID- 9030908
TI  - Inhibition by abruquinone A of phosphoinositide-specific phospholipase C
      activation in rat neutrophils.
AB  - In rat neutrophils, formyl-Met-Leu-Phe (fMLP)-induced phosphate formation was
      inhibited by abruquinone A (IC50 value about 32.7 +/- 6.4 microM) as well as by a
      putative phospholipase C inhibitor, [6-[[17 beta-3-methoxyestra-1,3,5(10)-trien
      17-yl]amino]hexyl]-1H-pyrrole- 2,5-dione (U73122) (IC50 value about 11.3 +/- 1.2
      microM). The reduction in inositol phosphate levels appeared to reflect
      inhibition of phospholipase C activity because the hydrolysis of
      phosphatidylinositol 4,5-bisphosphate (PIP2) catalyzed by a soluble fraction from
      neutrophils was also inhibited by abruquinone A (IC50 value about 31.4 +/- 5.6
      microM) over the same range of concentrations. Although abruquinone A alone
      induced Ca2+ and Mn2+ influx into neutrophils in Ca(2+)-containing medium,
      abruquinone A, like U73122, inhibited Ca2+ release (IC50 value about 23.5 +/- 0.5
      microM) from internal stores in Ca(2+)-free medium. These results indicate that
      abruquinone A inhibits the activity of phosphoinositide-specific phospholipase C
      in neutrophils.

PMID- 9030909
TI  - Candesartan (CV-11974) dissociates slowly from the angiotensin AT1 receptor.
AB  - The mechanisms of the insurmountable antagonism of 2-ethoxy-1-[[2'-(1H-tetrazol-5
      yl)biphenyl-4-yl]methyl]1H-benzimid azole -7-carboxylic acid, candesartan (CV
      11974), an angiotensin AT1 receptor antagonist, on angiotensin II-induced rabbit
      aortic contraction were examined in contraction and binding studies.
      Preincubation of the rabbit aorta with CV-11974 (0.1 nM) for 30 min reduced the
      maximal contractile response to angiostensin II by approximately 50%. This
      insurmountable antagonism of CV-11974 was reversed in the presence of losartan (1
      microM), a surmountable angiotensin AT1 receptor antagonist. The inhibitory
      effect of CV-11974 on angiotensin II-induced contraction persisted longer after
      washing than did that of losartan but was irreversible. Scatchard analysis of
      [3H]CV-11974 binding in bovine adrenal cortical membranes indicated the existence
      of a single class of binding sites (Kd = 7.4 nM). Competition binding studies
      using angiotensin II receptor agonists and antagonists have demonstrated that
      [3H[CV-11974 binding sites may be identical to angiotensin AT1 receptors. The
      dissociation rate of [3H]CV-11974 binding (t1/2 = 66 min) was 5 times slower than
      that of [125I]angiotensin II binding (t1/2 = 12 min). These results suggest that
      the insurmountable antagonism by CV-11974 is due to its slow dissociation from
      angiotensin AT1 receptors.

PMID- 9030910
TI  - NMDA receptor 2C subunit is selectively decreased by MK-801 in the entorhinal
      cortex.
AB  - Administration of the non-competitive NMDA receptor antagonist MK-801 (5-methyl
      10,11-dihydro-5H-dibenzo[1,d]cyclohepten-5,10-imine) produces paradoxical
      neurotoxicity in limbic cortical regions which includes the entorhinal cortex.
      The expression of NMDAR-2C but not -2A, -2B or -2D subunits was significantly
      decreased in rat entorhinal cortex layer III following MK-801 administration.
      These results suggest an important role for the NMDAR-2C subunit in the response
      to MK-801-induced neurotoxicity in brain regions highly vulnerable to injury.

PMID- 9030937
TI  - Supraglottic hemilaryngopharyngectomy plus radiation for the treatment of early
      lateral margin and pyriform sinus carcinoma.
AB  - BACKGROUND: Supraglottic hemilaryngopharyngectomy is a functional procedure
      suitable for the treatment of carcinoma of the upper part of the pyriform sinus
      and carcinoma of the lateral laryngeal margin. It consists of resection of the
      supraglottic hemilarynx and ipsilateral pyriform sinus. METHODS: Forty-nine
      patients underwent this procedure from 1979 through 1994. The median age was 51
      (40-72). The data were collected by a review of patients' records. RESULTS: Two
      patients died in the postoperative period. The average time of removal of the
      nasogastric tube was 14 days. The survival rate at 3 years was 52% and at 5
      years, 47%. The local recurrence rate was 2%, the overall neck recurrence was
      15%, metastasis occurred in 15% of cases. CONCLUSIONS: Indications for this
      procedure are carcinoma of the upper part of the pyriform sinus and carcinoma of
      the laryngeal margin with normal vocal cord mobility.

PMID- 9030938
TI  - Variability of tumor volumes in T3-staged head and neck tumors.
AB  - BACKGROUND: The Tumor Node Metastasis (TNM) classification system describes head
      and neck tumors using anatomic or unidimensional criteria and may therefore fail
      to define the actual three-dimensional tumor bulk. To investigate this we
      measured variability of tumor volumes (Vvol) in T3-staged head and neck tumors.
      METHODS: Patient material consisted of pretreatment computerized tomography (CT)
      scans of 71 patients, seen between 1990 and 1995, with T3 head and neck carcinoma
      involving different subsites. Computerized tomographic scans of 42 patients
      displayed distinct tumor boundaries and were free of motion and/or dental
      artifacts. Using these scans, tumor volumes were measured using the summation-of
      areas technique, and Vvol was determined. RESULTS: Following are the tumor-volume
      measurements: T3 larynx carcinoma (n = 12) Vvol, 1.7-17.0 mL (median 3.7 mL); T3
      oropharynx carcinoma (n = 13) Vvol, 10.0-41.2 mL (median 18.3 mL); T3 hypopharynx
      carcinoma (n = 10) Vvol, 8.9-67.8 mL (median 17.4 mL); T3 nasopharynx carcinoma
      (n = 3) Vvol, 3.7-30.1 mL; T3 maxillary sinus carcinoma (n = 4) Vvol, 56.0-103.1
      mL. CONCLUSIONS: T3-Staged tumors of the head and neck show considerable
      variability of tumor volumes. Incorporation of tumor volume data may further
      refine the TNM staging system.

PMID- 9030939
TI  - Frequency and therapeutic implications of "skip metastases" in the neck from
      squamous carcinoma of the oral tongue.
AB  - BACKGROUND: Supraomohyoid neck dissection is an adequate operation for the
      elective treatment of the neck for patients with oral cavity cancer. Squamous
      cell carcinoma of the oral tongue, however, metastasize to clinically negative
      nodes in 20% to 30% of patients. These nodes usually are located in levels I-III.
      METHODS: The medical records of 277 previously untreated patients with squamous
      cell carcinoma of the oral tongue were reviewed between the years 1970 and 1990.
      All patients had a glossectomy and neck dissection as part of their initial
      treatment. Patients were evaluated as to the findings in their neck. The
      following group of patients were included: (1) patients who had level III nodes
      positive, without disease in levels I and II; (2) patients with disease in level
      IV; (3) patients with disease in level IIB or IIIB, and; (4) patients who were
      electively dissected and whose neck did not demonstrate any pathologically
      involved nodes, but level IV was not included in the dissection and the patient
      subsequently developed pathologically positive nodes in level IV. RESULTS: Of all
      patients, 15.8% had either level IV metastasis as the only manifestation of
      disease in the neck or the level III node was the only node present without
      disease in level I-II. CONCLUSION: The usual supraomohyoid neck dissection is
      inadequate for a complete pathologic evaluation of all the nodes at risk for
      patients with squamous carcinoma of the oral tongue. This may create a dilemma in
      determining whether postoperative radiotherapy is necessary. Consequently, all
      patients with squamous cell carcinoma of the oral tongue should have levels I-IV
      nodes removed if an elective neck dissection is part of their initial therapy.

PMID- 9030940
TI  - Nucleolar organizer regions and prognosis in glottic squamous cell carcinoma.
AB  - BACKGROUND: The quantity of nucleolar organizer regions (AgNORs) appear to be
      prognostic significant in several tumor types. METHODS: Sections from 93
      routinely processed pretreatment biopsies from patients with glottic carcinomas
      were stained by silver nitrate and evaluated by two counting methods: (1) the
      mean number of AgNOR per tumor nucleus (mAgNOR), and (2) the number of tumor
      nuclei with one, two, three, four, and more than four AgNOR grains. From these
      figures the percentage of nuclei with one, two or less, three or less, and four
      or less AgNORs (pAgNOR1, aAgNOR < or = 2 etc) were calculated. RESULTS: The
      median mAgNOR was 4.3, and low counts correlated favorably with the disease-free
      period (p = 0.0433). The median percentages for pAgNORs were 14, 26, 38, and 51
      for pAgNor1, PAgNOR < or = 2, pAgNor < or = 3 and pAgNOR, < or = 4 respectively.
      Values above the medians correlated positively with the disease-free period (p
      values ranging from 0.0005 to 0.0001). Although pAgNOR < or = 3 appeared to be
      the best discriminator by multivariate analysis, pAgNOR1 is the method of choice
      because this parameter is the easiest and quickest to perform. CONCLUSION: pAgNOR
      counts appear to be a potent prognostic marker and may become useful in treatment
      decisions.

PMID- 9030941
TI  - Autofluorescence characteristics of oral mucosa.
AB  - BACKGROUND: The fluorescence characteristics of tissues depend upon their
      biochemical composition and histomorphological architecture, both of which
      undergo a change during malignant transformation. These changes are detectable as
      an alteration in the fluorescence spectral profile of the tissues. METHODS:
      Biopsy specimens from clinically suspicious lesions and normal-appearing oral
      mucosa were obtained from patients. Fluorescence spectroscopic measurements were
      obtained to study the differences between normal and dysplastic tissues and to
      determine the most appropriate excitation wavelength(s) for exploiting these
      differences. RESULTS: Fluorescence spectra from a total of 12 histologically
      normal (healthy mucosa or benign lesions) and ten abnormal (dysplastic or
      malignant) tissue samples were compared. Significant spectral differences were
      seen between the two groups. These differences were most marked at the excitation
      wavelength of 410 nm. Using this wavelength, fluorescence correctly diagnosed 20
      of 22 samples studied. CONCLUSIONS: This technique accurately differentiates
      normal from abnormal tissues in vitro and has the potential applications for in
      vivo use as a noninvasive diagnostic tool.

PMID- 9030942
TI  - The distally based lateral arm flap for intraoral soft tissue reconstruction.
AB  - BACKGROUND: The radial forearm flap is probably the most frequently used among
      free flaps for intraoral soft tissue reconstruction. However, this flap is not
      always available. The other fasciocutaneous flaps may be too bulky or less
      pliable or may have a short vascular pedicle; their use is therefore less than
      ideal. We present a variant of the lateral arm flap located distally to the
      lateral epicondyle and having the same advantages as the radial forearm flap.
      METHODS: Vascular study (dissection and radiography) was previously undertaken to
      determine the vascular anastomotic network in the epicondylar area, between the
      posterior radial collateral artery and recurrent arteries running in front of the
      lateral epicondyle. This demonstrated the possibility of taking a skin paddle on
      and below the lateral epicondyle, based on the proximal pedicle. RESULTS: We used
      this flap on three patients for intraoral soft tissue reconstruction (tonsil,
      floor of the mouth, and piriform sinus). No complication with the flap itself was
      encountered. In all cases, direct closure of the donor site was possible, with no
      local complication. CONCLUSION: The distal lateral arm flap (LAF) represents an
      interesting and reliable alternative to the fasciocutaneous radial forearm flap.
      The positioning of the skin paddle over the lateral epicondyle and the proximal
      third of the lateral aspect of the forearm increases pedicle length, thus
      avoiding the use of vein grafts. Dissection is straightforward with a reliable
      vascular anatomy. Moreover, in this area, the limited amount of subcutaneous
      fatty tissue ensures easier placement and more pliability when compared with the
      standard LAF.

PMID- 9030943
TI  - Transverse process of the atlas(C1)--an important surgical landmark of the upper
      neck.
AB  - BACKGROUND: The internal carotid artery, the internal jugular vein, and the
      spinal accessory nerve are the main structures that are preserved in conservative
      neck dissections. In the upper neck, one surgical landmark used to find these
      structures is the transverse process of a cervical vertebral body. There is
      controversy about the origin of the transverse process in the upper neck.
      METHODS: We applied three-dimensional computerized tomography (3-D CT), an
      intraoperative navigational system and cadaver dissection of the neck to clarify
      the controversy. RESULTS: The origin of the transverse process was from the atlas
      (C1). CONCLUSIONS: The transverse process of the atlas is an important surgical
      landmark in the upper neck. The neurovascular bundle is located anteriorly. The
      transverse process of the axis (C2) is less prominent and is situated antero
      inferior to the spinal accessory nerve where the nerve emerges from the posterior
      border of the internal jugular vein.

PMID- 9030944
TI  - Palliative treatment with low-dose continuous infusion 5-fluorouracil in
      recurrent and/or metastatic undifferentiated nasopharyngeal carcinoma type.
AB  - BACKGROUND: Low-dose protracted continuous infusion (CI) 5-fluorouracil (5-FU),
      as proposed by Lokich et al, has been reported to be active and well tolerated in
      colorectal and breast cancers. We initiated a phase II trial with CI 5-FU in
      heavily pretreated undifferentiated carcinoma of the nasopharyngeal type (UCNT)
      patients in February 1989. METHODS: Twenty-one UCNT patients with recurrent
      and/or metastatic disease were treated with CI 5-FU (300 mg/m2) for 6 consecutive
      weeks. Treatment was to be continued until disease progression. RESULTS: Toxicity
      was mild. Diarrhea and mucositis (WHO grade 2 or greater) were seen in 4 (20%)
      and 6 patients (30%), respectively. Myelosuppression was infrequent, with only
      one patient with bone marrow invasion, experiencing grade 3 leukopenia. Two
      complete and 3 partial responses were obtained in 20 evaluable patients
      (ORR:25%). The median time to progression was 4 months (range 2-14); The median
      survival for the whole population was 10 months (avg 2-41). CONCLUSION: This
      appears to be a useful palliative treatment for heavily pretreated UCNT patients.

PMID- 9030945
TI  - Nerve paralysis after surgery in the submandibular triangle: review of University
      of Tokyo Hospital experience.
AB  - BACKGROUND: We assessed the incidence of neural complications in submandibular
      surgery in relation to the type of surgery, experience of the surgeon, and other
      factors. METHODS: We retrospectively reviewed the records of 133 patients who
      underwent excision of the submandibular triangle components at the University of
      Tokyo Hospital during the last 19 years. RESULTS: The most frequent complication
      was mandibular branch paralysis. Excluding 12 patients with malignant tumors,
      facial weakness was present postoperatively in 29.8% (37) or 124 resections. All
      palsies subsequently resolved. The paralysis was more frequent when nerve
      identification was performed than when it was not. CONCLUSIONS: The cardinal
      factors in minimizing incidence of nerve damage are an understanding of the
      anatomy of the nerves, low and generous skin incision, awareness of orientation
      in the surgical planes, avoidance of the use of metal retractors, and avoidance
      of elaborate identification of the nerve.

PMID- 9030946
TI  - Subglottic paraganglioma.
AB  - Paragangliomas are uncommon neuroendocrine tumors. In the head and neck region
      they are most commonly associated with the carotid body, vagus nerve,
      jugulotympanic paraganglia, and occasionally the superior and inferior laryngeal
      paraganglia. Laryngeal paragangliomas and subglottic paragangliomas are rare.
      There have been nine reported cases in the English literature of subglottic
      paragangliomas. We present a case of this unusual lesion and discuss histologic
      characteristics and surgical treatment.

PMID- 9030947
TI  - Postirradiation laryngeal osteosarcoma: case report and literature review.
AB  - BACKGROUND: Laryngeal sarcoma is a rare disease entity. In review of the
      literature, chondrosarcoma is the most common sarcoma, followed by fibrosarcoma.
      Osteosarcoma is very rare; there are only seven cases reported in the literature.
      Postirradiation sarcoma is a late complication of radiotherapy. Osteosarcoma is
      the most common type in this group. The larynx is often involved in the radiation
      field of treatment for head and neck malignancies. However, postirradiation
      laryngeal osteosarcoma has not yet been reported. METHODS: We present a 56-year
      old man who under went radiotherapy for nasopharyngeal carcinoma 32 years ago and
      later developed a laryngeal osteosarcoma. RESULTS: The patient underwent total
      laryngectomy but died 1 year and 9 months later with locally extensive disease.
      CONCLUSIONS: We report the first case of postirradiation laryngeal osteosarcoma.
      In addition to surgical treatment, adjunctive therapies should be considered for
      this group of patients.

PMID- 9030948
TI  - Vascular leiomyoma of the superior turbinate: first reported case.
AB  - BACKGROUND: Vascular leiomyoma is an uncommon smooth muscle tumor rarely found in
      the head and neck area. We report the first case arising for the superior
      turbinate of the nasal cavity. METHODS: A case presentation, treatment, and
      review of the literature are discussed. RESULTS: Twenty-one months after
      embolization and surgical resection, the patient is doing well, without evidence
      or recurrence. CONCLUSIONS: Vascular leiomyoma is a rare benign tumor of the
      nasal cavity, and surgical excision yields high cure rates.

PMID- 9030950
TI  - Fibrous histiocytoma of the lacrimal sac.
AB  - BACKGROUND: Fibrous histiocytoma is a slow-growing tumor that most commonly
      occurs in the superficial and deep soft tissue, with an occasional occurrence in
      the orbit. However, fibrous histiocytoma of the lacrimal sac is very rare.
      METHODS: A case report of a 33-year-old man with a palpable mass in the right
      lacrimal sac and epiphora is presented, with a review of the literature
      pertaining to this unusual case. RESULTS: The patient was found to have a 3 x 2
      cm-sized mass in the right lacrimal sac. Under the impression of benign tumor,
      the tumor was excised. Histopathological diagnosis of fibrous histiocytoma was
      made on the surgical specimen. Following surgical treatment, the patient has
      remained free of symptoms. CONCLUSIONS: Fibrous histiocytoma of the lacrimal sac
      is a rare disease. This case report and a review of the literature demonstrated
      that surgical excision appears to control the tumor.

PMID- 9030949
TI  - Free gastro-omental flap reconstruction of the complex, irradiated pharyngeal
      wound.
AB  - BACKGROUND: Reconstruction of the complex pharyngeal wound after radiotherapy
      presents a surgical challenge. METHODS: Evaluation of the gastro-omental flap in
      the reconstruction of the pharynx and overlying soft tissue after local flap
      failure. RESULTS: A 70-year-old patient underwent a total laryngectomy and
      radical neck dissection after 70 Gy of external beam radiotherapy for an advanced
      squamous cell carcinoma of the pyriform sinus. Postoperatively, a large
      pharyngocutaneous fistula developed. Attempted closure with a pectoralis major
      flap was unsuccessful. A tubed gastro-omental free flap based on the right
      gastroepiploic vessels was used to reconstruct the pharynx. The accompanying
      greater omentum was skin grafted after filling the large soft tissue defect in
      the neck. The wounds healed primarily, and oral alimentation was resumed on the
      seventh postoperative day. CONCLUSIONS: The gastro-omental flap is a versatile
      composite flap which can provide mucosal lining as well as abundant soft tissue.
      It should be considered a secondary option in irradiated, complex pharyngeal
      wounds when local flaps are not available to be used in conjunction with free
      jujunal transfer.

PMID- 9030959
TI  - Quality control procedures for flow cytometric applications in the hematology
      laboratory.
AB  - Clinical diagnosis is one of the areas in which flow cytometry (FCM) has gained
      wide popularity and FCM now plays a crucial role in several aspects of medical
      hematology. It has progressively replaced many traditional laboratory tests due
      to its greater accuracy, sensitivity and rapidity. Unfortunately, among the very
      large number of its potential applications, only a minority of flow cytometric
      protocols have been standardized. Numerous factors are responsible for variation
      in analytical conditions and may affect results obtained by FCM. All these
      variables can be schematically divided into three major groups: factors related
      to the biological samples, immunological and accessory reagent factors and
      factors associated with the use of instruments. The quality control program must
      monitor and evaluate all aspects of the procedure. This includes the following
      main aspects: 1) performance of the flow cytometer, 2) specimen collection,
      transportation and maintenance of its integrity, 3) reagents, particularly
      monoclonal antibodies and 4) sample measurements, data acquisition and their
      interpretation. Procedures described here are designed to assess all the settings
      which affect the reliability, reproducibility and sensitivity of the cytometer in
      order to ensure identical conditions on a daily basis.

PMID- 9030960
TI  - Immunophenotypic characterization of acute leukemias and chronic
      lymphoproliferative disorders: practical recommendations and classifications.
AB  - Immunophenotypic characterization of leukemic cells has become essential for the
      diagnosis of acute leukemias (AL) and chronic lymphoproliferative disorders
      (CLPD). Immunophenotyping allows to classify AL according to (i) lineage
      assignment of the leukemic clone based on the degree of specificity (or "score")
      of expressed markers, (ii) the differentiation level of the clone and (iii) the
      presence of irrelevant markers. In addition, some rare AL subtypes may be
      identified, such as M0, M6 "variant" and M7 FAB types, as well as "biphenotypic"
      (hybrid) AL. Finally particular immunophenotypic profiles are of pronostic value
      or associated with specific cytogenetic abnormalities. In leukemic phase CLPD
      setting, some circulating lymphoid cell immunophenotypic profiles are strongly
      correlated with morphology as defined by the FAB and REAL classifications. In
      addition, some marker expressions are of pronostic value. However, proper choices
      of sample nature, monoclonal antibodies and immunophenotyping methods are
      essential to improve quality, reliability and reproducibility of the results and
      must be carefully controlled in and between laboratories.

PMID- 9030961
TI  - Reticulocyte analysis using flow cytometry.
AB  - Automation of the reticulocyte count by means of flow cytometry has considerably
      improved the quality of this investigation. This article deals firstly with the
      reasons for the poor performance of the microscopic technique and with the
      physiological principles underlying identification and classification of
      reticulocytes using RNA labeling. It then outlines the automated methods
      currently on the market, which can be classified in three categories: a) "general
      purpose" cytofluorometers, which in clinical laboratories usually deal with
      lymphocyte immunophenotyping; b) the only commercially available cytofluorometer
      dedicated to the reticulocyte count; this automat has the advantage of requiring
      no human intervention as it merely needs to be fed with samples; c) hematology
      analyzers with specific modules for automatic counting of reticulocytes
      previously incubated with a non-fluorescent dye. Of the various fluorescent
      markers available, thiazole orange, DEQTC iodide and auramine are most often used
      for this basic hematology test. The quality of the count, the availability of new
      reticulocyte indices (maturation index, percentage of young reticulocytes) and
      rapidity of the count give this test renewed value in the practical approach to
      the diagnosis of anemia, and also open new perspectives in the surveillance of
      aplastic anemia after chemotherapy or bone marrow grafting.

PMID- 9030962
TI  - Flow cytometry study of cell cycle, apoptosis and drug resistance in acute
      leukemia.
AB  - The response to therapy of leukemic cells is largely determined by their capacity
      of proliferation and apoptosis in presence of the administered drugs. We describe
      here the main markers used in flow cytometry (FCM) and involved in the assessment
      of cell cycle parameters: single labeling by Propidium Iodide (PI) and double
      labeling anti-Bromodeoxyuridine (BrdUrd)/PI which, both in vitro and in vivo,
      gives cell percentages in the different cell cycle phases. The markers of cell
      cycle progression can be divided into proliferation markers such as PCNA
      (proliferating cell nuclear antigen) or Ki-67 and cell cycle progression markers.
      The latter, which are the core of the cell cycle machinery, are molecules
      recently characterized (Cyclins, CDKs (cell dependent kinases), CDIs (cyclin
      dependent kinase inhibitors)) and their cell expression can be analyzed using
      FCM. FCM is also one of the best means to detect and quantitate apoptotic cells.
      Several techniques are described: Nuclear labeling using Hoechst 33342:
      mitochondrial labeling using DiOC6(3): detection of DNA fragmentation using 1)
      labeling of fixed and permeabilized cells with a DNA marker or 2) labeling of the
      free 3' DNA ends using incorporation of labeled deoxynucleotides; detection in
      apoptotic cells (Bcl-2, Fas, phospholipids...). At last, we analyzed flow
      cytometry methods to study the cell resistance to Ara-C and anthracyclins. In
      combination with cell kinetic studies and detection of apoptotic cells, they
      should increase the efficiency of the acute leukemia treatment.

PMID- 9030963
TI  - Flow cytometry for CD34 determination in hematopoietic grafts.
AB  - CD34 is a type I transmembrane protein that is expressed on lympho-hematopoietic
      progenitor and endothelial cells and has a potential adhesion function. Various
      monoclonal antibodies, whether characterized by glycosylated epitopes or not, are
      utilized to recognize different subsets of hematopoietic progenitors.
      Coexpression of membrane markers involving CD34 is an approach to the definition
      of those subpopulations of cells previously characterized by using in vitro
      cultures. Thus, in the autologous transplantation procedure, flow cytometry
      determination of CD34+ cells in the grafts themselves, especially as concerns
      cytapheresis products, was enhanced with CFU-GM enumeration. This methodology
      required a standardized protocol with regard to the choice of the monoclonal
      antibody, had to be to data acquisition and to computer analysis. Within the
      framework of a multicentric trial, various strategies had to be evaluated.
      Special attention was paid to obtaining a sensitivity level of 0.1%. New,
      standardized approaches are currently in the planning stage, in particular with a
      view to determining absolute count on the basis of readings generated by the flow
      cytometer.

PMID- 9030964
TI  - Flow cytometry assessment of leukocyte functions in vascular pathologies.
AB  - Intravascular activation of leukocytes has been shown to be involved in a wide
      range of different and apparently unrelated clinical situations, such as systemic
      inflammatory response syndrome, ischemia/reperfusion, disseminated intravascular
      coagulation, atherosclerosis... All of them involve to different degrees many
      steps of the inflammation process, with leukocyte accumulation and release of
      toxic species. Haemostasis, leukocyte functions and their cross-talk are
      summarized in this paper, as well as the most popular methods used for studying
      leukocyte functions in vascular pathologies. The strengths and present
      limitations of flow cytometry are analyzed in comparison with the biochemical and
      functional approaches.

PMID- 9030965
TI  - Priming study of human phagocytes oxidative burst by using flow cytometry.
AB  - In response to a variety of stimuli, e.g. pathogens, phagocytes release reactive
      oxygen species which are essential for bacterial killing and also potentiate
      inflammatory reactions. We have used flow cytometry measurements to study the
      priming process of phagocyte oxidative burst in whole blood, in order to avoid
      introducing artefacts due to the purification process and to stimulate the in
      vivo situation more closely. In these conditions, we examined the in vitro
      effects of proinflammatory cytokines (TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, IL
      8 and GM-CSF) on the PMN oxidative burst. We found that none of the cytokine
      tested directly activated the PMN oxidative burst. In contrast, TNF, GM-CSF and
      IL-8 strongly primed a subpopulation of PMN which produced large amounts of H2O2
      in response to fMLP, suggesting that these cytokines may play a critical role in
      bactericidal killing in vivo. Furthermore, we reported a decreased H2O2
      production by TNF or IL-8 primed PMN in HIV-infected patients. This impairment,
      which correlated with the clinical stage of the disease, could contribute to the
      increased susceptibility to bacterial infections in HIV-infected patients. In
      addition, we reported the case of a child with severe recurrent infections due to
      intracellular microorganisms which could be related to an impairment of the
      phagocyte priming process of the oxidative burst [corrected].

PMID- 9030966
TI  - Muscle force and endurance in untreated and human growth hormone or insulin-like
      growth factor-I-treated patients with growth hormone deficiency or Laron
      syndrome.
AB  - Muscle force and endurance of four muscle groups (biceps, triceps, hamstrings and
      quadriceps) were measured by a computerized device in three groups: (A) 4 boys
      with isolated growth hormone deficiencies (IGHD) examined before at 10 and 24
      months of hGH treatment; (B) 5 children (2 F, 3 M) with Laron syndrome were
      examined 3.5-4 years after initiation of insulin-like growth factor-I (IGF-I)
      treatment, and (C) comprised 8 untreated adults (5 F, 3 M) with Laron syndrome.
      For each patient, 2 matched controls, by age, sex, physical activity and height
      below the 50th percentile, were examined. GH- or IGF-I-deficient patients before
      treatment revealed reduced muscle force and endurance. GH treatment (0.6
      U/kg/week) restored muscle force and endurance, progressively, mainly in the boys
      with puberty. Three to 4 years of IGF-I treatment (150 micrograms/kg/day) in
      patients with Laron syndrome proved to have a weaker effect than GH in restoring
      muscle force. The difference in effectiveness between hGH and IGF-I in restoring
      muscle force may be due to either the more marked muscle underdevelopment in
      Laron syndrome patients than in patients with IGHD or a difference in action
      potential between the two hormones.

PMID- 9030967
TI  - No genetic mutation in type II 3 beta-hydroxysteroid dehydrogenase gene in
      patients with biochemical evidence of enzyme deficiency.
AB  - Nonclassic or the mild form of 3 beta-hydroxysteroid dehydrogenase (NC3 beta-HSD)
      deficiency is an entity which is identified with typical features of premature
      pubarche, hirsutism, or oligomenorrhea. In this study, type II 3 beta-HSD gene
      from 4 girls who were diagnosed as NC3 beta-HSD deficient, base on the adrenal
      steroidogenic responses to ACTH, was analyzed to determine whether NC3 beta-HSD
      deficiency was an allelic variant of classical 3 beta-HSD deficiency by
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). We
      could not detect any alterations of type II 3 beta-HSD gene from these patients.
      Our result strongly suggests that unlike classical 3 beta-HSD deficiency, NC3
      beta-HSD deficiency may be secondary adrenal biosynthetic defects, rather than
      dual inherited deficiencies.

PMID- 9030968
TI  - Final height of girls with central precocious puberty, untreated versus treated
      with cyproterone acetate or GnRH analogue. A comparative study with re-evaluation
      of predictions by the Bayley-Pinneau method.
AB  - This study was designed to determine the benefit of therapy on final height (FHt)
      in girls with central precocious puberty (CPP). A total of 102 patients were
      evaluated--28 untreated, 26 treated with cyproterone acetate (CyA), and 48
      treated with GnRH analogue (GnRHA)-and their achieved FHt was compared to the
      respective target height (THt). Of the untreated girls, half (14/28) had a slow
      course of puberty and reached THt +/- 0.5 SD (FHt 160.2 +/- 7.1, THt 159.5 +/-
      6.6 cm); the other half (14/28) had an accelerated course of puberty with a FHt
      well below THt (FHt 150.8 +/- 4.3, THt, 159.2 +/- 5.9 cm) and in most cases
      (14/28) below the height-SDS of both parents. The treated girls (both regimens)
      reached THt above (CyA group: FHt 157.8 +/- 5.1, THt 156.8 +/- 5.1 cm; GnRHA
      group: 159.6 +/- 6.3, THt 157.7 +/- 5.7 cm). We conclude that without treatment
      the FHt of girls with CPP may be significantly compromised and that therapy is
      more beneficial if started before bone age exceeds 12 years. Our data also showed
      that for final height predictions in CPP the Bayley and Pinneau tables for
      average children should be used, regardless of the advanced bone age of the
      patients.

PMID- 9030969
TI  - Assessment of red blood cell indices in growth-hormone-treated children.
AB  - In order to evaluate the effect of growth hormone (GH) on erythropoiesis, red
      blood cell (RBC) indices (hemoglobin, Hb; hematocrit, Ht; RBC count, and mean
      corpuscular volume, MCV) of 19 GH-deficient children (12 with isolated GH
      deficiency and 7 with multiple pituitary hormone deficiencies) between 2 months
      and 15 years of age were compared to those of 57 sex- and age-matched short
      normal controls before starting treatment with recombinant human GH (rhGH). The
      RBC indices were expressed as standard deviation score (SDS). Moreover, the RBC
      indices in the GH-deficient group were analyzed after the first 3 and 6 months of
      GH treatment and compared to those of 9 Ullrich-Turner syndrome (UTS) patients
      with GH therapy. Both patients with isolated and those with multiple pituitary
      hormone deficiencies presented significantly lower values of Hb-SDS (-1.6 +/- 1.0
      and -2.0 +/- 1.4, respectively; p = 0.004), Ht-SDS (-1.55 +/- 0.9 and -2.5 +/-
      2.1, respectively; p = 0.001) and RBC-SDS (-0.6 +/- 1.6 and -1.2 +/- 0.9,
      respectively; p = 0.002) when compared to controls (Hb-SDS: -0.6 +/- 1.4; Ht-SDS:
      -0.1 +/- 1.9; RBC-SDS: 0.17 +/- 1), in the presence of comparable MCV-SDS values.
      In contrast, RBC indices did not differ between patients with isolated and those
      with multiple pituitary hormone deficiencies. When the variations of RBC indices
      were analyzed after 3 and 6 months of rhGH therapy in the 19 GH-deficient
      children, an increase in the Hb-SDS (p = 0.01), Ht-SDS (p = 0.03) and RBC-SDS was
      observed, indicating an early stimulatory effect on RBC proliferation in these
      patients. However, an analysis of the RBC indices in the group of UTS patients
      did not reveal any significant change after both 3 and 6 months of therapy with
      rhGh. The increase in Hb, Ht, and RBC count observed during GH treatment confirms
      the in vivo erythropoietic growth-promoting effects of GH. However, this effect
      seems to be related only to conditions of GH deficiency. When GH deficiency is
      associated with multiple pituitary hormone deficiencies there are pathological
      influences on erythropoiesis which are not corrected until Gh treatment is
      started, indicating a 'permissive' role of GH in the hematopoietic system.

PMID- 9030970
TI  - Short- and long-term (final height) growth responses to growth hormone (GH)
      therapy in patients with Turner syndrome: correlation of growth response to
      stimulated GH levels, spontaneous GH secretion, and karyotype.
AB  - In 41 girls with Turner syndrome, the growth hormone (GH) peak values during
      stimulation tests and parameters of spontaneous nocturnal GH secretion were
      studied and compared with respect to different karyotypes, short-term growth
      response to GH therapy, and final height. 22.0% of the girls tested had a
      subnormal (peak < 11 ng/ml) and 9.7% a pathological (< 7 ng/ml) GH response. The
      spontaneous GH secretion showed a good correlation with the data of the
      provocation tests, providing no further information regarding GH capacity. Short
      term growth response to GH treatment could not be predicted by any of the
      investigated parameters. Although patients with isochromosomes had frequent
      subnormal GH tests, their growth response to GH treatment after 1 year was
      comparable to that of girls with XO karyotype and mosaicism. In 18 patients who
      had reached final height, the height gain during treatment (calculated as final
      height minus projected adult height) was not different among patients with
      normal, subnormal, or pathological GH tests. In contrast, final height minus
      projected adult height in 4 girls with isochromosomes was 15.7 +/- 5.1 versus 7.6
      +/- 3.3 cm in 14 patients with other karyotypes (p < 0.01). These girls had a
      more pronounced bone age delay (3.3 +/- 0.3 vs. 1.8 +/- 1.2 years) at the start
      of therapy and thus a better growth potential. We conclude that short- and long
      term growth responses to GH treatment in Turner syndrome could not be predicted
      by GH testing. Patients with isochromosomes might represent a subpopulation which
      is more frequently GH deficient and shows a marked bone age delay.

PMID- 9030971
TI  - Effect of different serum concentrations of growth hormone-binding protein (GHBP)
      on the regulation of GH receptor/GHBP gene transcription in a human hepatoma cell
      line.
AB  - Although high-affinity growth hormone (GH)-binding protein (GHBP) seems to mirror
      tissue GH receptor (GH-R) status and effects GH kinetics, the physiological
      importance and ultimate biological role of GHBP remain largely unknown and
      obscure. Therefore, the aims of this study were, first, to test the hypothesis
      that different serum concentrations of GHBP may regulate GH-R/GHBP gene
      transcription and, second, to define a new nonradioactive polymerase chain
      reaction (PCR) method to quantify GH-R/GHBP mRNA levels which was to compare with
      the RNase protection assay. Sera from patients with Laron-type dwarfism (n = 10)
      and adult obese patients (n = 7) containing distinct GH and GHBP concentrations
      were added to human hepatoma cells (HuH 7) cultured in a hormonally-adapted
      medium. GH-R/GHBP gene expression was studied 3 h after the addition of the sera.
      The results of the regulated GH-R/GHBP mRNA levels imply a direct impact of GHBP
      on GH-R/GHBP gene transcription under these circumstances. In conclusion, we set
      up a nonradioactive quantitative PCR method which enables the measurement and
      quantification of GH-R/GHBP mRNA. The results were identical with the data
      obtained using RNase protection assay. In addition, these results provide
      evidence that GHBP may have some effect on the regulation of the GH-R/GHBP
      transcription and that it is more than simply a shed or secreted product with
      extracellular destinations and functions. Our personal view, therefore, is that
      GHBP is rather an active player than an erratic extracellular domain of a
      receptor.

PMID- 9030972
TI  - Diabetes insipidus due to hypophysitis.
AB  - Central diabetes insipidus is a chronic disorder which in most patients occurs
      secondary to tumor, infection, trauma or other lesions. In about 20-30% of
      patients etiology is unclear, however a destructive autoimmune process in the
      hypophysis may play a role. We report the case of an 18-year-old girl with
      central diabetes insipidus. Vasopressin levels were typically decreased.
      Examinations performed 1.5 years after manifestation showed no pathologic changes
      on MRI and no additional endocrine disorder. MRI was repeated 1.5 years later
      whereon a thickening of the pituitary stalk as a typical sign of hypophysitis was
      apparent. No other reasons could be found for the vasopressin deficiency. The
      finding of hypophysitis in our patient 3 years after disease manifestation
      suggests that the characteristic MRI changes may take as long as 3 years to
      become apparent.

PMID- 9030973
TI  - Report of an XX male with hypospadias and pubertal gynecomastia, SRY gene
      negative in blood leukocytes but SRY gene positive in testicular cells.
AB  - Most XX male subjects present an anomalous translocation of the sex-determining
      region of the chromosome Y (SRY) gene from chromosome Y to chromosome X. Several
      explanations have been proposed for the differentiation of testicular tissue in
      the absence of SRY gene. A patient is presented in whom the SRY gene was absent
      in peripheral leukocytes but present in testicular tissue. This possibility
      should always be ruled out before diagnosing Y-negative XX maleness.

PMID- 9030974
TI  - Genomic structure of human BST-1.
AB  - BST-1 is an ectoenzyme expressed on human bone marrow Stromal cells and myeloid
      lineage cells, having both ADP-ribosyl cyclase and cyclic ADP-ribose (cADPR)
      hydrolase activities. In mouse, BST-1 is also expressed on lymphoid progenitors.
      We isolated chromosomal DNA segments of the human BST-1 gene. The human BST-1
      gene consisted of nine exons and eight introns. The length of each exon was very
      similar to that of the Aplysia ADP-ribosyl cyclase gene. The flanking region of
      the BST-1 gene contained several potential binding sites for nuclear factors, NF
      kappa B, p53, NF-IL6, CREB, PEA3, E2A, C/EBP, AP3, AP2 and SP1 and consensus
      sequences for gamma-IRE and ISRE like element.

PMID- 9030975
TI  - Functional characterization of NK1.1 + Ly-6C+ cells.
AB  - It was found that NK1.1+ cells were subdivided by their different expression
      pattern of Ly-6C antigen. To characterize their functional significance in
      immunoregulation, we separated NK1.1 + Ly6C+ cells and NK1.1 + Ly-6C- cells from
      C57BL/6 mouse nylon-passed spleen cells by FACStar. Both NK1.1 + Ly-6C+ and NK1.1
      + Ly-6C- cells responded to the stimulation with IL-2 plus IL-12 and showed
      strong cytotoxicity against YAC-1 cells. However, these cells revealed different
      ability in terms of IFN-gamma production. Only NK1.1 + Ly-6C+ cells, but not
      NK1.1 + Ly-6C- cells, cultured with IL-12 alone or IL-2 plus IL-12, produced high
      levels of IFN-gamma. Flow cytometric analysis demonstrated that NK1.1 + Ly-6C+
      cells consisted of NK1.1 + CD3-Ly-6C+ NK cells and NK1.1 + CD3 + Ly-6C+ NKT
      cells. Therefore, we further separated these two populations from NK1.1 + Ly-6C+
      cells to define their functions. Although, both NK1.1 + CD3-Ly-6C+ NK cells and
      NK1.1 + CD3+ NKT cells showed the same level of cytotoxicity. It was clearly
      demonstrated that NK1.1 + CD3+Ly-6C+ NKT cells were major immunoregulatory cells
      to produce IFN-gamma in respond to IL-12 alone or IL-2 plus IL-12.

PMID- 9030976
TI  - Schistosoma mansoni-infected mice show augmented hepatic fibrosis and selective
      inhibition of liver cytokine production after treatment with anti-NK1.1
      antibodies.
AB  - Gamma interferon (IFN-gamma) plays an immunoregulatory role at different stages
      of the experimental Schistosoma mansoni-driven processes in mice through its
      ability to induce cell cytotoxicity against the parasite larvae and to reduce
      established hepatic fibrosis. The role of Natural Killer (NK) cells, as possible
      major source of IFN-gamma, has never been studied during the entire course of
      murine schistosomiasis. In this paper, we investigated the consequences of in
      vivo NK cell depletion, maintained during 17 weeks of infection, on both hepatic
      granuloma development and immunological parameters. We found that NK cell
      depletion following anti-NK1.1 monoclonal antibody (mAb) injections led to an
      increase of hepatic collagen content in the late stages of granuloma formation
      and to the diminution of interleukin 12 (IL-12) p40 and IL-7 mRNA expression in
      the livers. The hepatic mRNA expression of other cytokines (IFN-gamma, tumor
      necrosis factor alpha [TNF-alpha] and IL-4), as well as humoral and cytokine
      responses in sera, were not significantly different between control monoclonal
      antibody (CmAb) and anti-NK1.1-treated mice. Thus, we demonstrate that the anti
      NK1.1 treatment might induce alterations of regulatory mechanisms, detectable at
      a late stage of a chronic process in immunocompetent mice.

PMID- 9030977
TI  - Attempts to demonstrate indirect T cell allorecognition of donor MHC peptides in
      transplant patients.
AB  - Indirect T cell allorecognition has been shown to play an important role in the
      rejection of allografts in experimental animals. Although there has been much
      speculation as to its role in clinical transplantation, especially with regard to
      chronic rejection, indirect T cell allorecognition has been difficult to
      demonstrate in transplant patients. In this paper, we looked for in vitro T cell
      proliferation to synthetic peptides corresponding to donor HLA-A and HLA-B
      incompatible antigens. Twelve 15 amino acid peptides corresponding to the
      hypervariable regions of six of the most common HLA class I alleles in Caucasian
      populations (A1, A2, A3, B7, B8 and B44) were studied. Blood was taken from 12
      adult patients following one or more episodes of acute kidney graft rejection,
      and from three pediatric patients undergoing chronic rejection of heart/lung
      transplants. The donor-recipient combinations were selected such that at least
      one of the six HLA antigens above was present in the donor and absent in the
      recipient. Peripheral blood mononuclear cells from these patients responded
      strongly in proliferation assays to phytohemagglutinin. However, none responded
      to the incompatible donor HLA peptides. Compartmentalization of responding T
      cells, the effects of immunosuppression, and assay sensitivity are discussed as
      possible explanations for the negative results.

PMID- 9030978
TI  - Effects of activating and deactivating cytokines on the functionally linked
      tetrahydrobiopterin. No pathways in vascular smooth muscle cells.
AB  - The functional relationship of nitric oxide (NO) production and synthesis of
      tetrahydrobiopterin (BH4), the requisite cofactor for NO synthase, was
      investigated in rat aortic smooth muscles cells (SMC). Inflammatory cytokines
      induced BH4 and NO synthesis in different ratios, IL-1 beta induced mainly NO
      synthesis with concomitant but limiting amounts of BH4 for maximal NO production.
      TNF alpha did not induce NO synthesis but induced BH4 synthesis. IFN gamma was
      ineffective on both the induction of NO and BH4 synthesis. TGF beta downregulated
      NO production but did not affect BH4 biosynthesis. IL-4 and IL-10 had no effect
      on both BH4 and NO synthesis. Activating cytokines strongly synergized in
      induction of NO production, whereas endogenous BH4 production became insufficient
      for maximal NO synthesis. Exogenous cofactor in the form of sepiapterin or
      authentic BH4, but not the natural isomer 7-BH4, enhanced NO production twofold.
      Inhibition of BH4 synthesis with dicumarol abolished NO production that could be
      restored in the presence of BH4.

PMID- 9030979
TI  - External glycopeptide binding to MHC class-I in relation to expression of TAP
      transporters, beta 2-microglobulin and to pH.
AB  - MHC class-I binding glycopeptides are easily visualized on the cell surface by
      carbohydrate specific monoclonal antibodies. By comparing the staining intensity
      between anti-carbohydrate and anti-MHC class-I specific monoclonal antibodies, an
      estimation of the fraction of peptide accessible 'empty' sites on the cell
      surface of MHC class-I molecules can be made. This system was used to analyze
      glycopeptide binding to MHC class-I molecules in relation to transporter
      associated with antigen processing (TAP) peptide transporters and beta 2-M
      expression, using gene targeted mice, and in relation to pH. Approximately 15,
      40, and 95% 'empty' Db molecules were found on activated T cells from normal,
      beta 2-M-/- and TAP -/- mice, respectively. The ASN9-6h-Gal2 glycopeptide also
      bound to transfected 'empty' Db molecules on T1-Db, T2-Db and T3-Db cells with a
      preference for T2-Db cells, lacking TAP peptide transporters. The stability of
      glycopeptide binding to H-2Db is also highest on T2-Db cells. pH was found to
      influence binding either positively or negatively, using four different
      glycopeptides, binding either to Db or Kb. We conclude that external glycopeptide
      binding may reflect important functional properties in the MHC class-I system and
      that pH in different processing compartments might influence the expressed
      peptide repertoire.

PMID- 9030980
TI  - Human macrophages respond to LPS in a serum-independent, CD14-dependent manner.
AB  - Two crucial mediators of monocyte activation by lipopolysaccharide (LPS) are the
      acute phase plasma factor, lipopolysaccharide binding protein (LBP) and cell
      surface-expressed CD14. Whether macrophage (M phi) recognized and respond to LPS
      in a similar manner is unknown. Here we show that human monocyte-derived M phi
      respond to LPS by tumor necrosis factor-alpha release and procoagulant activity
      upregulation by a similar dose response curve in the presence or absence of
      serum, suggesting that humoral factors such as LBP are relatively unimportant in
      the activation of M phi. Both serum-dependent and serum-independent activation of
      M phi by LPS require cellular CD14, as evidence by blocking studies with CD14
      specific antibodies. Clones from the monocytoid cell line Mono Mac-6 selected for
      high LPS sensitivity displayed similar properties. When washed free of serum and
      cultured in the presence of calcitriol, they responded to LPS in a similar
      manner, regardless of the presence or absence of serum, and this response was
      inhibited by anti-CD14. It is hypothesized that during their differentiation. M
      phi acquire a functional substitute for the serum factor LBP, thereby being able
      to recognize low LPS concentrations in a milieu low in LBP concentration. It will
      be of interest to determine whether this is a high-affinity LBP receptor, LBP
      itself, or another cell surface constituent.

PMID- 9030981
TI  - B-CLL cells experimentally infected with EBV enter DNA synthesis, produce
      cytokines and stimulate T-lymphocytes.
AB  - Several B-chronic lymphocytic leukemia (B-CLL) clones, represented by different
      patients can be infected with EBV in vitro. A proportion of the cells becomes
      activated by the virus, but they rarely yield immortalized cell lines. We used
      cells from two B-CLL patients which differed in sensitivity to EBV infection.
      After 7 days in culture, we studied the CLL cells exposed to the B-cell
      activators Staphylococcus aureus, IL-2 and/or to EBV for expression of the
      activation markers CD23, CD39 and the adhesion and costimulatory molecules CD54
      and CD80, for DNA synthesis, for production of various cytokines and for capacity
      to stimulate autologous and allogeneic T-lymphocytes. Generally the frequency of
      cells expressing cytokines in the cytoplasm correlated with the activation status
      of the populations and with their capacity to stimulate T-cells. It is likely
      that the difference between the clones with regard to sensitivity to the viral
      infection, is determined by the maturation state of the CLL cells. It may
      therefore reflect the variation in the response within a normal B-cell
      population. The results obtained in the present and in our earlier experiments
      with EBV provide information concerning the events after primary EBV infection in
      vivo. The T-lymphocyte stimulatory capacity of the infected CLL cells may be
      considered as an in vitro correlate to the syndrome of infectious mononucleosis.
      The detection of cytokines in the infected B-CLL cells suggests that their
      production by the B-blasts contributes to the level of T-lymphocytosis induced by
      the primary infection.

PMID- 9030982
TI  - Constitutive biological activity of thymus-independent TCR-alpha-beta+ intestinal
      intraepithelial lymphocytes in TCR-alpha-/- gene disruption mice.
AB  - The surface of alpha beta T cells express a heterodimeric T cell receptor (TCR)
      composed of an alpha- and a beta-chain. In TCR-alpha gene disruption mutant mice,
      T cells can be identified which surface-express the TCR-beta chain in the absence
      of the TCR-alpha chain. Characteristically, intestinal intraepithelial
      lymphocytes (i-IELs) constitutively express biological functions which are
      demonstrable after TCR ligation by mAb. We here describe a small, but distinct
      population of TCR-alpha-beta+ i-IEL in TCR-alpha-/- mice. These cells used a
      restricted V beta repertoire skewed towards V beta 8 or V beta 14 and most of
      them expressed the CD4 coreceptor. TCR-beta ligation by specific mAb induced
      cytolytic activity in these TCR-alpha-beta+ i-IELs. Our findings reveal that TCR
      alpha-beta+ i-IELs express biological activities and suggest that they develop
      independent of the thymus.

PMID- 9030984
TI  - Mediterranean lymphoma: back to the original idea of mucosa-associated lymphoid
      tissue lymphoma.

PMID- 9030983
TI  - In vivo molecular analysis of cytokines in a murine model of ocular
      onchocerciasis. I. Up-regulation of IL-4 and IL-5 mRNAs and not IL-2 and IFN
      gamma mRNAs in the cornea due to experimental interstitial keratitis.
AB  - Sclerosing keratitis is the major cause of blindness due to onchocerciasis which
      results from chronic infection with the filarial parasite Onchocerca volvulus.
      Using a murine model of onchocercal sclerosing keratitis, we have demonstrated
      previously that predominantly (> 85%) CD3 + /CD4+ T-cells as well as the IL-2
      receptor bearing cells infiltrate into the cornea in vivo during development and
      progress of the disease. The identification of CD4+ subsets TH1 and TH2 based on
      the cytokine secretion patterns of murine T-lymphocytes has been useful for
      understanding the immune basis of resistance and pathogenesis in murine models of
      several parasitic diseases. The present investigation was carried out to
      demonstrate whether the local immune response at the corneal lesion due to
      onchocercal interstitial keratitis correlated with such distinct patterns of
      cytokine production. For that purpose, mRNA was extracted separately from corneas
      obtained from the diseased eyes and the normal eyes of A/J mice with onchocercal
      interstitial keratitis, reverse transcribed and amplified by the polymerase chain
      reaction with four different cytokine specific primers. In corneas obtained from
      the eyes affected with onchocercal interstitial keratitis, mRNAs coding for IL-4
      and IL-5 were up-regulated compared to the normal eyes having no lesions from the
      same animals. However, the levels of mRNAs for IL-2 and IFN gamma were found to
      be the same in the diseased and normal eyes. Taken together, these data suggest
      that IL-4 and IL-5 producing TH2-lymphocytes are active at the corneal lesion due
      to onchocercal interstitial keratitis.

PMID- 9030985
TI  - Variant forms of primary aldosteronism: reconsideration of the differential
      diagnosis and treatment.

PMID- 9030986
TI  - Disodium cromoglycate as a controller for asthma.

PMID- 9030987
TI  - Mitochondria DNA mutations induce variable clinical symptoms including "stroke"
      in younger and aged persons.

PMID- 9030988
TI  - Paraneoplastic neurologic syndromes.
AB  - Paraneoplastic neurologic syndromes are degenerative diseases of the central or
      peripheral nervous system that develop in association with a systemic neoplasm
      without a direct invasion by tumor. The pathogenesis of this disorder has been
      hypothesized in the past, and now there is increasing evidence that autoimmune
      processes triggered by the underlying neoplasm play a major role in the
      pathophysiology, as documented by many reports of identification of
      autoantibodies that react with both the target neural tissue and the underlying
      neoplasm, as evidenced by the extensive application of molecular biology
      techniques. The presence of antibodies in serum or CSF of some patients with this
      disorder now accurately identifies the subgroup of the disorders related to
      specific neoplasms. The trend of recent studies on the pathogenesis of this
      disease may in the future lead to a new era to clarify the pathogenesis.

PMID- 9030989
TI  - Neoadjuvant chemotherapy in scirrhous cancer of the stomach using uracil and
      tegafur and cisplatin.
AB  - We administered a mixture of uracil and tegafur (UFT)/cisplatin (CDDP)
      chemotherapy in 28 patients with scirrhous gastric cancer. In the regimen, UFT
      was orally administered at a dose of 200 mg/m2 twice a day. The CDDP was
      administered at a dose of 90 mg/m2 by 24-hour continuous infusion every 4 weeks.
      As a result, antitumor effects for primary gastric foci were achieved in 14 of
      the 28 patients (50%). Ascites from peritoneal dissemination disappeared
      completely in eight of 13 patients (62%). Total gastrectomy was performed in ten
      patients after 2 to 3 courses of chemotherapy. Histological response grades
      assessed on the resected specimen were Grade 2 in four, Grade 1b in three, Grade
      1a in one and Grade 0 in two patients. Neoadjuvant chemotherapy is feasible
      against scirrhous gastric cancer and a subsequent prospective randomized trial
      should be prepared to clarify the survival benefit of the treatment.

PMID- 9030990
TI  - Carotid artery disease in patients with retinal artery occlusion.
AB  - Embolization from the carotid bifurcation has been proposed as the most common
      cause of central retinal artery occlusion (CRAO) and branch retinal artery
      occlusion (BRAO). The purpose of this study was to evaluate carotid artery
      disease in patients with CRAO and BRAO. Using carotid ultrasonography, 17
      patients (13 males, 4 females, mean age 68.7 +/- 7.1 years) with CRAO and BRAO
      were examined for stenotic findings and plaque morphology (homogeneous or
      heterogeneous) within 7 days after onset. The internal carotid artery (ICA)
      ipsilateral to the affected side showed a significantly higher incidence of
      severe carotid stenosis as compared to the non-affected side. The occurrence of
      heterogeneous plaques in the ICA did not differ between the affected and the non
      important affected side. We suspect that severe carotid stenosis in addition to
      heterogeneous plaques plays an important role in retinal artery occlusion.

PMID- 9030991
TI  - Influence of cisapride on the pharmacokinetics and antihypertensive effect of
      sustained-release nifedipine.
AB  - To investigate the clinical significance of interactions between cisapride and
      sustained-release nifedipine, we compared the plasma nifedipine concentration and
      blood pressure after administration of nifedipine alone (20 mg) with those
      obtained after administration of nifedipine cisapride (2.5 mg) in 20 patients
      with hypertension. The plasma nifedipine level was not altered by cisapride at
      one hour after administration, but was significantly increased at two (p < 0.01),
      three (p < 0.01), and four (p < 0.05) hours when compared with the level measured
      after nifedipine alone. Cisapride significantly decreased the mean blood pressure
      at three hours (p < 0.05) after administration of nifedipine. The acetaminophen
      method was used to determine gastric emptying time. The plasma concentration of
      acetaminophen at 45 minutes after administration was significantly increased by
      cisapride, suggesting that enhanced gastrointestinal motility might be the basis
      for the increase in the plasma nifedipine concentration. These results suggest
      that enhancement of the antihypertensive effect of nifedipine can occur when the
      drug is prescribed with cisapride, and that caution is needed when using such a
      combination therapy.

PMID- 9030992
TI  - Clinical presentation of pulmonary tuberculosis associated with acquired
      immunodeficiency syndrome in metropolitan Tokyo.
AB  - The clinical features of pulmonary tuberculosis associated with acquired
      immunodeficiency syndrome (AIDS) in Japan were surveyed utilizing questionnaires
      completed by 48 institutes around the Tokyo metropolitan area. We found 11
      Japanese and six foreign patients. The average number of patients per institute
      was 0.37. The Japanese patients had advanced human immunodeficiency virus (HIV)
      infection. A middle aged man, with fever and cough, nonspecific chest X-ray
      infiltrates, decreased lymphocyte counts, and a negative tuberculin skin test was
      the typical presentation of the Japanese patients. The clinical diagnosis was
      often difficult. The smear positive rate was high among those from whom smears
      were obtained, suggesting high communicability. None of the isolates indicated
      multidrug-resistant tuberculosis at the time of diagnosis. In conclusion, sputum
      smear and culture remain the keys to diagnosing tuberculosis in patients with
      AIDS, although the clinical picture may be atypical for pulmonary tuberculosis.

PMID- 9030993
TI  - Carcinoid tumor of the gall bladder.
AB  - A classical carcinoid tumor, measuring 11 x 17 mm, was found in a 41-year-old
      woman in the neck of the gall bladder. The lesion infiltrated the muscular layer
      of the gall bladder wall. Histologically, the tumor was positive for only
      Grimelius and chromogranin A stains. In a literature search, approximately half
      of the tumors reported as gall bladder carcinoid tumor appear to be actually
      endocrine cell carcinomas, which are completely different from classical
      carcinoid tumors with respect to size, metastasis and prognosis. These carcinomas
      should not be termed as carcinoid tumors from both the clinical and histological
      points of view, and should be clearly distinguished from benign lesions when
      reported.

PMID- 9030994
TI  - Crohn's disease associated with colo-bronchial fistula.
AB  - An 18-year-old female patient with Crohn's disease presented with left lower lobe
      pneumonia and pleural effusion which were resistant to treatment with
      antibiotics. Colo-bronchial fistula had not been recognized until she coughed up
      yellow sputa with feculent odor and developed acute respiratory distress
      syndrome. This type of fistula is a rare complication of Crohn's disease, but the
      present case certainly alerts physicians to search for a fistula between the
      bronchus and gastrointestinal tract when encountering patients with Crohn's
      disease accompanied by antibiotic-resistant chronic pneumonia.

PMID- 9030995
TI  - "Mediterranean lymphoma" treated with antibiotics.
AB  - We report a case of Mediterranean lymphoma treated with antibiotics. A 74-year
      old woman visited the hospital due to abdominal pain. Endoscopic examination
      showed erosions and ulcerations on duodenal mucosa. Biopsy specimens
      histologically revealed massive infiltration of small-sized lymphocytes and
      plasma cells in subepithelial mucosa. Immunoperoxidase staining showed that the
      infiltrating cells were positively stained with anti-alpha heavy chain. Serum IgA
      concentration was elevated and immunoelectrophoresis of the serum demonstrated
      monoclonal protein composed of alpha heavy chain. During the antibiotic treatment
      her symptoms disappeared and serum IgA concentration was normalized. Endoscopic
      examination also showed healing of the duodenal ulceration. The similarities
      between Mediterranean lymphoma and gastric mucosa-associated lymphoid tissue
      (MALT) type lymphoma, both of which may be related to bacterial infection and can
      be treated with antibiotics, are discussed in this report.

PMID- 9030996
TI  - Sudden death during Holter electrocardiogram monitoring in a patient with variant
      angina.
AB  - We report a case of sudden death due to variant angina during Holter
      electrocardiogram (ECG) monitoring. The patient, a 60-year-old man, had been
      aware of chest discomfort lasting less than one minute at midnight 2 days
      earlier. Because variant angina or arrhythmia was suspected, Holter ECG
      monitoring was performed. The patient spent a whole day without a recurrence of
      chest pain before going to bed, but at midnight he developed sudden chest pain,
      and died immediately after taking a sublingual tablet of isosorbide-dinitrite.
      Analysis of the Holter ECG revealed ventricular fibrillation after several
      ventricular premature beats following ST-segment elevation in both the CM5 and
      NASA leads. This case shows that sudden death from variant angina may occur
      within a few days after the first onset, and also highlights whether priority
      should be given to making a definite diagnosis or giving treatment when variant
      angina is strongly suspected.

PMID- 9030997
TI  - Primary aldosteronism with bilateral multiple aldosterone-producing adrenal
      adenomas.
AB  - A 41-year-old woman developed primary aldosteronism due to bilateral multiple
      aldosterone-producing adenomas (APA). She was suspected to have idiopathic
      hyperaldosteronism (IHA) 7 years previously. Although preoperative data suggest
      APA and IHA was suspected in a postoperative microscopic specimen, a definite
      clinical diagnosis could not be made. Cytochrome P-450 and other enzymes involved
      in aldosterone synthesis were found in the tumor portions but not in the zona
      glomerulosa of attached adrenals, which histopathologically showed "paradoxical
      hyperplasia". This was a rare case of bilateral multiple APA, which could be
      differentiated from IHA by immunohistochemical analysis of adrenal steroidogenic
      enzymes.

PMID- 9030999
TI  - Two cases of severe bronchiectasis successfully treated with a prolonged course
      of trimethoprim/sulfamethoxazole.
AB  - Two patients with severe bronchiectasis, one patient without other disease and
      the other with hyper IgE syndrome, were successfully treated with long-term
      therapy with low doses of trimethoprim and sulfamethoxazole (TMP-SMZ). Recurrent
      respiratory infections with productive cough and high fever were resistant to
      various antibiotics and often disturbed the patients' activities in daily life.
      However, they showed marked improvement following TMP-SMZ therapy, which was
      started for methicillin-resistant Staphylococcus aureus (MRSA) infection. MRSA
      disappeared some months later, but Pseudomonas aeruginosa appeared again in the
      sputum. Both patients, however, have remained free from symptoms for over one
      year.

PMID- 9030998
TI  - Near-death asthmatic reaction induced by disodium cromoglycate.
AB  - A near-death asthmatic reaction was induced by disodium cromoglycate (DSCG) as
      evidenced by positive skin and inhalation provocation tests. The patient's
      history revealed an episode of exacerbation by inhalation of DSCG. In spite of
      such an experience, he inhaled DSCG for relief of asthmatic attack, resulting in
      near-death exacerbation. This patient emphasizes the need to re-recognize that
      DSCG is not a reliever and the DSCG could cause fatal asthma.

PMID- 9031000
TI  - Esophagomediastinal fistula as a complication of tuberculous mediastinal
      lymphadenitis.
AB  - In a 44-year-old female esophagomediastinal fistula was found secondary to
      tuberculous mediastinal lymphadenitis. Chest computed tomography revealed
      amorphous air collection in the subcarinal region of the mediastinum with
      mediastinal lymphadenopathy. Esophagography with gastrografin confirmed
      esophagomediastinal fistula. The patient was treated with antituberculous therapy
      with rifampicin, isoniazid, pyrazinamide and ethambutol, resulting in resolution
      of the esophagomediastinal fistula and mediastinal lymphadenopathy.

PMID- 9031001
TI  - Evans' syndrome associated with Graves' disease.
AB  - A 36-year-old woman who had had Graves' disease for 6 years was admitted with
      severe thrombocytopenia. Evans' syndrome was diagnosed. The patient's family
      history showed multiple cases of Graves' disease but no cases of Evans' syndrome.
      Both conditions in this patient improved with corticosteroid and thiamazole
      therapy. Several autoimmune antibodies were found, but a common autoimmune
      mechanism was not clearly shown. Although the combination of Graves' disease and
      Evans' syndrome had not occurred previously in her family, genetic factors may
      play an important role in the pathogenesis of both conditions.

PMID- 9031002
TI  - Mitochondrial encephalomyopathy with elderly onset of stroke-like episodes.
AB  - A 52-year-old woman with a history of a hearing disturbance since age 20
      experienced visual hallucinations and convulsions, followed by right hemiparesis
      and aphasia. On the basis of a muscle biopsy and mitochondrial DNA analysis, she
      was diagnosed as mitochondrial myopathy, encephalopathy, lactic acidosis, and
      stroke-like episodes (MELAS). This case is unique in that the stroke-like
      episodes occurred 30 years after disease onset.

PMID- 9031003
TI  - Guillain-Barre syndrome and ethylene diamine tetraacetic acid-dependent
      pseudothrombocytopenia associated with mumps.
AB  - A 35-year-old man with Guillain-Barre syndrome and ethylene diamine tetraacetic
      acid (EDTA)-dependent pseudothrombocytopenia associated with serologically
      confirmed mumps is presented. A polyneuropathy developed 18 days after the onset
      of mumps, that improved with plasmapheresis. A decreased platelet count was
      observed 25 days after the onset of mumps attributed to platelet agglutination in
      blood anticoagulated with EDTA, and the agglutination was prevented by other
      anticoagulants. Guillain-Barre syndrome associated with mumps is rare and EDTA
      dependent pseudothrombocytopenia following mumps has never been documented. This
      represents the first report of Guillain-Barre syndrome and EDTA-dependent
      pseudothrombocytopenia following mumps. Furthermore, our findings suggest
      activation of the humoral immune response as a potential pathogenesis.

PMID- 9031004
TI  - Loneliness among the oldest old, a comparison between residents living in nursing
      homes and residents living in the community.
AB  - Two groups of individuals, eighty years of age or older, were compared with
      respect to the experience of loneliness and the influence of social
      relationships. One group was living in nursing homes. The other group was living
      alone in their own homes in the community. There were no significant differences
      in experienced loneliness between residence with close contacts with members of
      family and friends compared to residents without such contacts in either of the
      two groups, with one exception: institutional residents with existing contacts
      with former neighbors reported significantly lower levels of loneliness compared
      to institutional residents without such contacts. Frequency of contacts with
      family and neighbors did not influence significantly the degree of loneliness for
      residents in institutions. For residents in the community there were significant
      differences in experienced loneliness between those who had frequent contacts
      with family members and neighbors and those with infrequent contacts.
      Institutional residents, like residents in the community who desired more
      frequent contacts with family members and friends, reported higher levels of
      loneliness, compared to those who reported sufficient contacts.

PMID- 9031005
TI  - Correlates of perceived social support and equality of interpersonal
      relationships at mid-life.
AB  - An investigation into the correlates of perceived social support and the equality
      of interpersonal relationships at mid-life was conducted using a sample of 3954
      adults from the University of North Carolina Alumni Heart Study (UNCAHS).
      Participants ranged in age from forty to fifty years. Results suggested that
      while the number of family roles and social activities are the same for men and
      women, women perceive a greater availability of social support and report they
      give more than they take in relationships with family. There was no association
      found between the perceived availability of social support and global indices of
      equality of interpersonal relationships; suggesting an independence between these
      two psychological aspects of social support. Further, multiple regression
      correlational analyses indicated gender, level of social activity, and self
      esteem as significant predictors of perceived social support; with self-esteem
      being the best single predictor. Relatedly, gender and number of children were
      found to be significant predictors of the perceived equality of relationships
      with family. These findings suggest differences in mid-life men and women's
      psychological perception of the availability of social support, and the give and
      take of relationships with family.

PMID- 9031006
TI  - Disclosure of basic strengths and basic weaknesses in demented patients during
      morning care, before and after staff training: analysis of video-recordings by
      means of the Erikson theory of "eight stages of man".
AB  - In the field of care for aging persons, it is commonly understood that
      personality changes occur in dementia patients. It is reported to be a consistent
      part of the clinical syndrome and to occur early in the disease. The aim of this
      study was to investigate if strengths and weaknesses, described by E.H. and J.M.
      Erikson as basic quality in the person, could be interpreted in severely demented
      patients during a caring activity, and if a difference in these qualities could
      be seen after staff completed a training program in "integrity promoting care."
      The morning care of five patients was video-recorded and a phenomenological
      hermeneutic analysis of the patient's and staff's interaction was conducted. The
      findings indicate that the complex qualities of someone's personality are more
      preserved than could be expected considering the cognitive handicap. It seems,
      however, that demented patients need a special, supportive environment for their
      full mental potential to be realized. It is reasonable to assume that, if the
      staff are given knowledge of how to create a positive climate for the demented
      patients and the opportunity to implement it, the patients will show a rich
      pattern of mental reactions in spite of their dementia.

PMID- 9031007
TI  - The impact of cognitively impaired patients and shift on nursing assistant
      stress.
AB  - This study compared the stress experienced by nursing assistants (NAs) under four
      work conditions: high or low proportion of cognitively impaired patients and day
      or other shift. Five standard measures of caregiver stress served as the
      dependent variables in this study; burden, reaction to patient behaviors,
      workload, and two measures of burnout. A 2x2 multivariate analysis of variance
      found an interaction effect of type and shift on the stress measures. Univariate
      tests found that Burden and Depersonalization accounted for this effect. A
      further multivariate analysis of simple main effects found significant
      differences for each independent variable within each level of the other
      independent variable. Univariate analysis found that NAs who care for cognitively
      impaired patients on the day shift show significantly higher scores on specific
      stress measures. The article concludes with a discussion of how institutions can
      respond to the stresses faced by NAs who care for cognitively impaired patients.

PMID- 9031008
TI  - The relationship of aging to self-esteem: the relative effects of maturation and
      role accumulation.
AB  - This research examines the relationship of age and two dimensions of self-esteem
      using a national sample of adults in the United States. The direct effects of age
      on self-worth and on self-efficacy are compared to the indirect effects of age on
      these through role accumulation. Findings indicate those over age sixty-five
      experience heightened levels of self-esteem, especially on self-efficacy,
      compared to their younger counterparts. However, through the intervening variable
      of role accumulation, older age is associated with decreases in self-esteem. The
      implications of these findings are discussed for maturational and role
      perspectives on the aging self, and a more general theory of self-esteem
      dimensions.

PMID- 9031009
TI  - The welfare state, pensions, privatization: the case of Social Security in the
      United States.
AB  - In all high-income nations, the welfare state is under challenge, with particular
      concern voiced about the burden of retirement pensions on the public fisc and on
      younger workers. The strongest drive against social insurance is taking place in
      the United States, which has less of it than other nations and appears to be in
      the best position to meet future entitlement claims. In this article, the author
      examines the liabilities that the U.S. Social Security system is likely to incur
      over the next 35 years and finds that there is little danger that the system will
      fall into insolvency. Privatizing Social Security is not necessary to assure the
      integrity of future pension benefits. Furthermore, the cost-benefit ratio of
      privatization appears to be unfavorable, as borne out by the mandatory private
      pension plan in effect in Chile. Some wealthy nations will face greater
      demographic strains than the United States, but all need to retain the welfare
      state as a foundation for future changes in the world of work.

PMID- 9031010
TI  - The state of neoliberalism in South Africa: economic, social, and health
      transformation in question.
AB  - Recent overhauls of the South African government's ruling machinery in the
      context of an ever-deepening commitment to neoliberal economic philosophy, have
      done serious, even irreparable harm to this country's political transformation.
      Notwithstanding some progress in policies adopted by the Department of Health,
      the March 1996 closure of the Reconstruction and Development Ministry and the
      subsequent announcement of a neoliberal macroeconomic policy have been cause for
      disgruntlement by those advocating progressive social and health policies.

PMID- 9031011
TI  - Give me discipline and give me death: neoliberalism and health in Chile.

PMID- 9031012
TI  - Impacts of the proposed restructuring of Medicare and Medicaid on the elderly: a
      conceptual framework and analysis.
AB  - The article examines the proposed transformations in U.S. Medicare and Medicaid
      as these are likely to affect the nation's elderly population. Drawing on
      political economy, moral economy, and notions of the deserving versus the
      undeserving poor, the authors develop a broad conceptual framework within which
      to better understand the current upheavals. Both Republican and Democratic
      proposals for restructuring Medicare and Medicaid are described and analyzed, and
      common themes within the various proposals highlighted. After exploring the
      differential impacts of the restructuring on subgroups within the elderly
      population, including low-income seniors, the disabled, women, and elders of
      color, the authors conclude with a discussion of the symbolic importance of the
      proposed transformations. The latter reflect both accelerated government movement
      away from its legitimation functions and toward increased capital accumulation,
      and continuing government attempts to reshape our perceptions of the state
      economy in ways that permit more radical cutbacks and austerity measures.

PMID- 9031013
TI  - The costs of mergers and acquisitions in the U.S. health care sector.
AB  - Important trends are emerging from evidence of health care industry concentration
      in the United States. Some of these are the durable consumer concerns--cost,
      choice, and access--which have received attention throughout the introduction of
      managed care. But with the intensified industry concentration, these have been
      joined by concerns about pricing power, control and quality, integrity of health
      system and health policy-making, and clashing institutional mandates. Such trends
      are particularly evident in the hospital and pharmaceutical industries.

PMID- 9031014
TI  - Beyond ideology: the emerging roles of New Zealand's crown health enterprises.
AB  - New Zealand has experienced radical public sector restructuring over the last
      decade, including the corporatization and subsequent privatization of state
      trading units and the reform of social services, including health. In 1991 a new
      government proposed and then implemented more radical health reforms, which
      included the corporatization of state-owned provider units (23 crown health
      enterprises) and the creation of an internal market with purchasers (four
      regional health authorities) separated from providers. Interviews with chief
      executives of crown health enterprises suggest that provider units are seeking a
      wider role than envisaged, with an interest in the health needs of their
      populations and undertaking some purchasing on their behalf. The purchasers see a
      narrower role for crown health enterprises. Both purchasers and providers report
      that competition between providers is not particularly helpful (and with only
      limited opportunities for this to occur), with collaboration being seen as more
      useful. Providers are critical of purchasers ability to adopt a strategic
      approach. Unlike other aspects of New Zealand's restructuring, there appears to
      be a retreat from some of the more radical facets of the reforms, reflecting both
      the resistance of the health sector and a newly uncertain political climate.

PMID- 9031015
TI  - Attempts to decentralize in recent Brazilian health policy: issues and problems,
      1988-1994.
AB  - Decentralization became an official policy in the Brazilian health sector after
      the fall of the military regime of 1964-1985. In this article the author reviews
      the concept and types of decentralization, with particular attention to the
      process of decentralization itself. There is a gap between the type of
      decentralization (devolution) called for in the national constitution and the
      deconcentration of activities actually implemented. This gap is explained by
      Brazil's centralist tradition and its supporters, staff resistance at the
      national level, and the weakness of local governments. Several methods could be
      used to redirect the reforms toward their original purpose, such as improving
      community participation, establishing a clear agenda for the decentralization
      process, and setting up some mechanisms to enhance this policy.

PMID- 9031016
TI  - The Oil, Chemical, and Atomic Workers International Union: refining strategies
      for labor.
AB  - In a period of declining union membership and severe economic and environmental
      crisis it is important that labor unions rethink their traditional roles and
      organizational goals. Responding to some of these problems and reflecting a
      history of innovative and progressive unionism, the Oil, Chemical and Atomic
      Workers Union (OCAW) has sought to address occupational and environmental health
      problems within the context of a political struggle. This study suggests that by
      joining with the environmental movement and community activists, by pursuing a
      strategy of coalition building, and by developing an initiative to build and
      advocate for a new political party, OCAW provides a model for reinvigorating
      trade unionism in the United States.

PMID- 9031017
TI  - The effects of race on the use of physician's services.
AB  - In recent years several studies have examined the role of race in determining
      both health care status and access to care. Most studies in this area have
      focused primarily on health care status, although the issue of access is often
      mentioned. While there are many reasons for differences in health status, access
      to resources may plan an important role. Using a Poisson regression, a
      decomposition analysis, and data from the 1987 National Medical Expenditure
      Survey, the authors of this article show that significant differences remain in
      the number of physician office visits for whites and African-Americans. The
      proportion of the racial differences in the number of office visits not explained
      by differences in objective factors is relatively large. In fact, the results
      show that a considerable part of the racial differential can be explained by
      differential responses to these objective factors. This implies that, even if all
      the objective factors that affect the demand for visits are equalized across
      race, significant differences in the utilization of health care services will
      remain.

PMID- 9031018
TI  - Prevalence and health implications of anti-gay discrimination: a study of black
      and white women and men in the CARDIA cohort. Coronary Artery Risk Development in
      Young Adults.
AB  - This study investigates the prevalence of self-reported experiences of
      discrimination based on sexual orientation among black and white women and men
      (25 to 37 years old) who are members of CARDIA, a multisite longitudinal study of
      cardiovascular risk factors. Among the 1,724 participants who responded to a 1989
      questionnaire obtaining data on lifetime number of sexual partners and who
      participated in the Year 7 exam (1992-1993), which included questions about
      discrimination, 204 (12 percent) reported having at least one same-sex sexual
      partner: 27 (7 percent) of the 412 black women, 13 (6 percent) of the 221 black
      men, 87 (14 percent) of the 619 white women, and 77 (16 percent) of the 472 white
      men. Among these four groups, 33, 39, 52, and 56 percent, respectively, reported
      having experience discrimination based on sexual orientation. Additionally, 85
      percent of black women and 77 percent of the black men reported having
      experienced racial discrimination, and 89 percent of the black women and 88
      percent of the white women reported having experience gender discrimination. In
      the light of research associating negative stressors with poor health outcomes,
      including elevated blood pressure, future studies should assess public health
      implications of discrimination based on sexual orientation, in conjunction with
      racial and gender discrimination.

PMID- 9031019
TI  - Using existing health care systems to respond to the AIDS epidemic: research and
      recommendations for Chile.
AB  - Chile is a country with a relatively low prevalence of HIV infection, where
      successful prevention has the potential to change the future course of the
      epidemic. A controversial national prevention strategy based upon public
      education has emerged in response to characterizations of the epidemic as well
      dispersed with a growing involvement of heterosexuals. This characterization is
      not consistent with the observed facts. There is a comparatively well-organized
      health care system in Santiago that is doing a good job of detecting HIV
      infection and already has in place the elements of a targeted intervention
      scheme. Chile should place priority on the use of the existing health care
      infrastructure for implementing both the traditional public health interventions
      for sexually transmitted diseases (contact tracing and partner notification) and
      the AIDS-necessitated strategy of focused counseling and education.

PMID- 9031020
TI  - A review of wound healing and wound dressing products.
AB  - A brief review of the literature concerning the wound healing process is
      presented. A synopsis of the physical and physiologic factors that can affect the
      rate of this process is provided. The authors discuss the importance of the wound
      dressing in maintaining an optimal environment for wound healing. Modern
      dressings have specific indications and are frequently comprised of more than one
      layer. The authors define the contact layers as the layer that comes into
      intimate contact with the wound surface and has the greatest influence on
      healing. A description of some of the common products used as the contact layer
      is presented.

PMID- 9031021
TI  - Austin/chevron osteotomy fixed with bioabsorbable poly-L-lactic acid single
      screw.
AB  - The authors propose a new bioabsorbable fixation device to be applied to V-shaped
      transverse osteotomies of the head of the first metatarsal (Austin-chevron
      osteotomies) for hallux valgus surgery. Namely, a 3.3-mm. diameter cortical screw
      made of poly-L-lactic acid. This screw was applied in 30 patients with an average
      age of 44 years (range: 20 to 61). A total of 35 osteotomies was performed. The
      study refers to the period between 1992 and 1994 with a mean follow-up of 18
      months (range: 12 to 36 months). The results of the study demonstrate good
      stability of the synthesis, with normal union (mean: 4 weeks), no adverse tissue
      reactions or osteolytic phenomena were noted. One patient developed avascular
      necrosis of the metatarsal head, which in the opinion of the authors, was not due
      to the device implanted. Over 90% of the patients were satisfied with both the
      aesthetic and functional results. The authors conclude that the poly-L-lactic
      acid cortical screw is a promising bioabsorbable fixation device for this
      corrective osteotomy in selected patients less than 50 years old, with good first
      metatarsal bone stock.

PMID- 9031023
TI  - Extensor hallucis longus tendon injury: an in-depth analysis and treatment
      protocol.
AB  - This article analyzes the controversial topic of whether or not to repair a
      lacerated extensor hallucis longus tendon. A literature review of extensor
      hallucis longus tendon injuries is presented. The authors then provide a
      treatment protocol for extensor hallucis tendon injuries.

PMID- 9031022
TI  - Clear cell hidradenoma of the second digit: a review of the literature with case
      presentation.
AB  - Clear cell hidradenoma is a well circumscribed and often encapsulated benign
      tumor of the dermis and subcutaneous tissue. These tumors have a low tendency
      toward ulceration, may vary in size, and have a low malignant potential. The
      treatment of choice is usually surgical excision. A literature review of this
      soft tissue tumor and a case history are presented.

PMID- 9031024
TI  - A quantitative assessment of healing sandals and postoperative shoes in
      offloading the neuropathic diabetic foot.
AB  - The purpose of this report is to compare plantar pressures between custom healing
      sandals and postoperative shoes using unmodified prescription shoe gear as a
      control. Using a repeat measures design, we recorded the plantar forefoot
      pressures of eight patients classified as diabetic foot category 1 (neuropathy,
      no significant deformity, no history of ulceration) with each ambulating in three
      devices: 1) unmodified prescription shoe gear, 2) postoperative shoe gear, and 3)
      a custom-fabricated healing sandal. Each subject served as his or her own
      control. The healing sandal significantly reduced plantar forefoot pressure in
      all areas of the forefoot except the fifth metatarsal head. The postoperative
      shoe did not significantly reduce pressure at any site in the forefoot when
      compared with unmodified prescription shoe gear.

PMID- 9031025
TI  - Osteonecrosis of the tibial and fibular sesamoids in an aerobics instructor.
AB  - Osteonecrosis of the sesamoids is a fairly uncommon clinical entity. The
      development of this condition involving both sesamoids has never been presented
      in the American literature. After extirpation of the sesamoids and interdigital
      fusion, the patient returned to her regular activities, including dance.

PMID- 9031026
TI  - Cost effectiveness of magnetic resonance imaging in diagnosing Pseudomonas
      aeruginosa infection after puncture wound.
AB  - This study was performed to determine the cost effectiveness of radiologic
      imaging studies in diagnosing Pseudomonas aeruginosa infections after puncture
      wounds and the respective comparison of imaging and scintigraphy. Using
      retrospective medical record review, we studied 12 patients with culture-proven
      Pseudomonas infections of bone, cartilage or joint, or soft tissues. Attention
      was paid to radiographic presentation, scintigraphic studies, and magnetic
      resonance imaging results. All available imaging studies were reviewed. A survey
      of the costs of each imaging study was conducted. All patients underwent surgery.
      Three patients had magnetic resonance imaging studies that provided definitive
      diagnosis of osteomyelitis and precise localization of involved bones, soft
      tissue edema, and periosteal abscess. Eight patients had bone scans, one of which
      was consistent with cellulitis; seven, with osteomyelitis; and two with no
      abnormalities. All patients had radiographs of the involved foot. Case 4 had
      three series of radiographs. Nine of the twelve patients (75%) had normal
      findings on radiographs, with only soft tissue swelling or osteoporosis. Five
      patients had evidence of osteomyelitis. Magnetic resonance imaging is a cost
      effective method in diagnosing Pseudomonas osteomyelitis. Early use of magnetic
      resonance imaging can provide definitive diagnosis and more precise anatomic
      localization necessary for surgical intervention.

PMID- 9031027
TI  - The "Z" osteotomy versus the Kalish osteotomy for the correction of hallux
      abducto valgus deformities: a retrospective analysis.
AB  - A retrospective analysis of hallux abducto valgus surgery performed between 1990
      and 1995 where the "Z" osteotomy and Kalish osteotomy were utilized was
      performed. Objective and subjective data were collected to determine the
      effectiveness of the Z osteotomy versus the Kalish osteotomy. Twenty cases of
      hallux abducto valgus where the Z osteotomy was utilized were evaluated on the
      basis of intermetatarsal angle correction and alleviation of preoperative
      symptoms. The same evaluation was performed on 21 cases where the Kalish
      osteotomy was utilized. There did not appear to be an appreciable difference in
      intermetatarsal angle correction between the two osteotomies; however, the Kalish
      osteotomy did alleviate preoperative symptoms to a greater degree compared with
      the Z osteotomy.

PMID- 9031028
TI  - Fibrosarcoma of the foot: a case presentation and review of the literature.
AB  - Fibrosarcomas make up a small percentage of soft somatic tissue malignancies.
      Fibrosarcomas of the foot and ankle constitute an even smaller percentage of all
      reported cases with respect to anatomic locations. The postoperative local
      recurrence is great, and the diagnosis is often difficult to make because of the
      similar microscopic presentation of plantar fibromatosis and fibrosarcoma. A case
      presentation of a plantar fibrosarcoma, after two failed attempts at excision,
      with a review of the literature, is discussed.

PMID- 9031029
TI  - Retrospective assessment of antibiotic and tourniquet use in an ambulatory
      surgery center.
AB  - In this study, 459 lower extremity surgeries were evaluated to assess and improve
      the quality of patient care at the Carnegie Surgery Center, Cleveland, Ohio. Two
      aspects of surgery were studied: the antibiotic usage and tourniquet application.
      The authors analyzed the rate of infection and the number of tourniquet
      complications that resulted from the surgeries. The infection rate was 0.65%, and
      there were no tourniquet complications. Using the information learned from the
      study and reviewing pertinent literature, recommendations were made to further
      enhance patient care.

PMID- 9031030
TI  - Dislocation of the tibialis posterior tendon: diagnosis and treatment.
AB  - Traumatic dislocation of the tibialis tendon occurred from minor ankle sprains in
      a 37-year-old male and a 53-year-old female. Both complained of local pain at the
      medial malleolus, and both walked with a limp. The diagnosis was suspected by
      clinical examination, in one case with 2 months' delay, and verified by
      ultrasound, computed tomography, and magnetic resonance imaging. The male patient
      was initially treated for an "uncomplicated ankle sprain." For various reasons
      surgery was delayed 4 months. During this interval the male patient complained of
      pain and severe dysfunction, requiring analgesic treatment. A medial Achilles
      tendon flap was used to support the repositioned tendon. The female patient was
      operated on within 1 week from injury, by resuturing of the retinaculum over the
      tendon. Postoperatively, both patients were immobilized with below-knee casts for
      6 weeks, allowing full weightbearing, followed by strength and stretching
      exercises. They were free of symptoms 2 and 3 months, respectively, after
      surgery. At follow-up 1 year postoperatively, both were asymptomatic and
      participated in activities like those before their injuries.

PMID- 9031031
TI  - The impact of gender on amputation.
AB  - The purpose of this report is to compare the proportion of lower extremity
      amputations among men and women with and without diabetes mellitus. We abstracted
      data from a database supplied by the State of New York for 14,555 nontraumatic
      amputations performed from 1990 through 1991, 58.8% of which were performed on
      patients with diabetes mellitus. We categorized amputations into three different
      levels (foot, leg, and thigh). Fifty-seven percent of the diabetes mellitus group
      were male, compared with 50% of the nondiabetic group. Men were younger than
      women regardless of the level of amputation in both the diabetic and nondiabetic
      population. Men with and without diabetes were significantly more likely to have
      a foot amputation, while diabetic and nondiabetic women were more likely to have
      a thigh amputation. When controlling for age, prevalence of vascular disease was
      not significantly different by gender in diabetic and nondiabetic groups at all
      amputation levels.

PMID- 9031032
TI  - Grand rounds: Haglund's deformity and retrocalcaneal intratendinous spurring.

PMID- 9031033
TI  - Bleomycin sulfate in the treatment of mosaic plantar verrucae.

PMID- 9031034
TI  - The misuse of the Lapidus procedure.

PMID- 9031035
TI  - The misuse of the Lapidus procedure.

PMID- 9031036
TI  - The misuse of the Lapidus procedure.

PMID- 9031037
TI  - The misuse of the Lapidus procedure.

PMID- 9031038
TI  - The hallucal interphalangeal sesamoid.

PMID- 9031039
TI  - Psoriasis and elective foot surgery.

PMID- 9031060
TI  - The molecular basis of hepatitis B e antigen (HBeAg)-negative infections.
AB  - Hepatitis B e antigen (HBeAg)-negative infections are an unusual form of chronic
      hepatitis B virus (HBV) infection in which viral replication and liver damage
      persist despite antibodies against HBeAg. This form of HBV may be associated with
      fulminant hepatitis. The molecular basis for an HBeAg-minus phenotype has been
      extensively studied and is most often a result of mutations in the precore
      region. However, other mutations can give rise to this phenotype and their
      investigation and characterization may reveal new insights into the pathogenesis
      of chronic viral hepatitis.

PMID- 9031061
TI  - The spectrum of extrahepatic manifestations in hepatitis C virus infection.
AB  - Infection with the hepatitis C virus affects not only the liver but also non
      hepatic tissues and may combine with many unrelated diseases and morbid
      conditions. A number of extrahepatic manifestations have already been recognized.
      For some of the extrahepatic disorders their association with HCV infection is
      well established while for others it remains probable or weak. Here, emphasis is
      given to the well-established extrahepatic manifestations of mixed
      cryoglobulinaemia, thyroid abnormalities and lichen planus as well as to the
      newly recognized association with diabetes mellitus, thrombocytopenia and the
      antiphospholipid syndrome. Pathogenetic mechanisms of extrahepatic and autoimmune
      features in HCV infection are still unclear and therapeutic decisions in such
      conditions are difficult. Data on the efficacy and side-effects of therapy with
      interferon-alpha and corticosteroids are reviewed and some practical guidelines
      for treatment are given.

PMID- 9031062
TI  - Transforming growth factor-beta 1 in chronic hepatitis C.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in mediating
      hepatic fibrogenesis and is known to have negative regulatory effects on the
      immune system. To analyse the effects of TGF-beta 1 in chronic HCV, serum samples
      were prospectively collected from 88 chronic hepatitis C virus (HCV) patients and
      34 healthy controls. Total and biologically active TGF-beta 1, interleukin (IL)-4
      and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). HCV RNA
      levels were quantified by branched DNA signal amplification pathway (bDNA), and
      HCV genotypes were determined by restriction fragment length polymorphism (RFLP)
      based on the 5'-untranslated region (UTR). Histological diagnosis was available
      in 87 patients, and liver sections from 80 other HCV patients were evaluated for
      hepatic expression of TGF-beta 1 using immunohistochemistry. Patients with
      chronic HCV infection had a higher level of TGF-beta 1, both total (817 +/- 464
      ng ml-1) and biologically active forms (520 +/- 370 pg ml-1), compared with
      controls (total TGF-beta 1 183 +/- 105 ng ml-1, P < 0.001; active TGF-beta 1 290
      +/- 140 pg ml-1, P < 0.01). There was no correlation between either total or
      biologically active TGF-beta 1 and clinical variables (age, gender, duration),
      liver biochemistry (serum alanine aminotransferase) or virological (HCV RNA
      level, genotype) parameters but there was a correlation between total TGF-beta 1
      and Knodell scores (P = 0.03, n = 54). However, when individual histological
      parameters were analysed, only the fibrosis score showed significant correlation
      (P = 0.04, n = 54). Immunohistochemistry revealed that 62% of HCV patients had
      TGF-beta 1 present in sinusoidal cells. No correlation existed between hepatic
      expression of TGF-beta 1 and any histological parameters. A trend existed towards
      a correlation between total TGF-beta 1 and IL-4 (P = 0.059, n = 74) but not with
      IL-10. Therefore, the TGF-beta 1 system is activated in chronic HCV infection and
      may contribute towards hepatic fibrogenesis; in addition, the TGF-beta 1 system
      may interact with IL-4.

PMID- 9031063
TI  - Hepatitis G virus infection: clinical characteristics and response to interferon.
AB  - A new member of the Flaviviridae family has recently been cloned and completely
      sequenced. The new virus, tentatively named hepatitis G virus (HGV) and known to
      be closely related to GB virus C (GBV-C), is transmitted by blood and blood
      products, intravenous drug use and other behaviour associated with a high risk of
      parenteral exposure to blood. The association of the virus with hepatitis is
      demonstrated by the presence of raised liver transaminase (alanine
      aminotransferase, ALT) levels in patients infected with HGV in the absence of
      other identifiable causes of hepatitis. No patient sera from groups exposed to
      blood and blood products were found to be positive when tested for the presence
      of GBV-A or GBV-B sequences, two other recently described flaviviruses. Forty
      five per cent of the HGV-infected patients investigated had normal ALT suggesting
      the existence of a normal carrier state. Persistent infection of up to 13 years
      duration was observed. Co-infection with hepatitis B or hepatitis C viruses (HBV
      and HCV) was commonly seen presumably because of shared risk factors. None of
      five patients with fulminant hepatic failure was positive for HGV infection. The
      virus is sensitive to interferon-alpha, but sustained responses were not seen
      with the treatment regimens used for HBV and HCV. Viral titres increased during
      immunosuppression following liver transplantation and the higher levels of
      viraemia were in one case accompanied by elavated ALT. Whether HGV (GBV-C)
      replicates in the liver in some or all cases remains to be established.
      Preliminary data suggest that it is present within peripheral blood lymphocytes.

PMID- 9031064
TI  - The clinical significance of the detection of hepatitis GBV-C RNA in the serum of
      patients with fulminant, presumed viral, hepatitis.
AB  - In a significant number of cases of fulminant (presumed viral) hepatitis
      worldwide, no aetiological agent has been identified. Recently, it has been
      suggested that a newly described flavivirus, GBV-C, is responsible for some of
      these cases. This study aimed to assess the clinical significance of GBV-C RNA,
      demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR), in the
      serum of patients with fulminant non-A to E hepatitis. Twenty-three consecutive
      cases of non-A to E fulminant hepatitis were included in the study. GBV-C RNA was
      reverse transcribed and amplified using two RT-PCR based detection methods.
      Medical records were examined to assess clinical history, duration and mode of
      infection, transfusion history, liver histology and clinical outcome. Five (three
      female, two male; mean age 21.2 years) of 23 patients had GBV-C RNA detected in
      their serum by RT-PCR: all five patients were RT-PCR positive following
      amplification by primers specific for the 5' non-coding region (NCR), whilst four
      were positive by primers for the NS3 region. Prior to the onset of illness, two
      patients had risk factors for transmission of an infectious agent; however, all
      five patients had been transfused during their illness, prior to testing for GBV
      C. Of these, two (of two in whom serum was available) were negative for GBV-C
      after the onset of fulminant hepatitis but before their first transfusion. This
      study does not support the hypothesis that the detection of hepatitis G virus
      (HGV)/GBV-C RNA in the serum of patients with fulminant hepatitis indicates a
      causal association. However, it does demonstrate that a careful transfusion
      history and screening of blood products is vital before the importance of GBV-C
      in the aetiology of fulminant hepatitis can be established.

PMID- 9031065
TI  - Severe hepatitis E infection during pregnancy.
AB  - In areas with endemic hepatitis E virus (HEV), acute liver failure secondary to
      hepatitis E infection is common in pregnancy and associated with a mortality rate
      of up to 20%. However, there is little information on the clinical course of
      severe hepatitis E infection during pregnancy in non-endemic areas such as the
      UK. Here we describe two cases of severe hepatitis E in pregnancy in patients
      returning from the Indian subcontinent. These cases were diagnosed by the
      detection of IgM anti-HEV antibody using an enzyme immunoassay with recombinant
      hepatitis E viral antigens. The first case describes acute hepatic failure, with
      coagulopathy and encephalopathy, warranting intensive therapy and elective
      ventilation. In the other case, the patient had severe hepatitis with
      coagulopathy. Both cases spontaneously resolved with no foetal loss. These cases
      highlight the need for suspicion of HEV infection in patients returning from
      endemic areas and presenting with acute non-A non-B hepatitis, especially when
      pregnant. Furthermore, the intensive treatment of acute liver failure caused by
      HEV may reduce the high mortality reported in Asia.

PMID- 9031066
TI  - Current prevalence of hepatitis A, B and C in a well-defined area in rural Crete,
      Greece.
AB  - A seroepidemiological study was carried out in a geographically well-defined area
      in rural Crete in order to determine the prevalence of A, B and C hepatitis
      markers in the local population. Serum samples were obtained from 257 subjects
      (94 males, 163 females), aged 15 years and over, who visited the primary health
      care services of the Spili Health Centre between July 1993 and March 1994, and
      from 164 subjects (83 males, 81 females) randomly selected from households in
      three neighbouring villages of the study area. In samples obtained from the Spili
      Health Centre, antibodies to hepatitis A virus (anti-HAV) were detected in
      234/244 (95.9%) subjects, antibodies to hepatitis B virus core antigen (HBcAb)
      were detected in 63/257 (24.5%) subjects and antibodies to hepatitis C virus
      (anti-HCV) were detected in 28/257 (10.9%) subjects. The corresponding figures
      for those randomly selected from the villages were 135/154 (87.7%), 16/164 (9.8%)
      and 5/164 (3%) respectively. Hepatitis B surface antigen (HBsAg) was positive in
      three (1.2%) subjects from the first group, while none of those recruited from
      the villages were positive for HBsAg. Interestingly, hepatitis markers were
      closely associated with age. No subjects under the age of 15 years showed
      evidence of prior hepatitis A infection and approximately 20% of those between 15
      and 44 years of age were also negative. By contrast, practically all subjects
      older than 44 years were anti-HAV positive. Similarly, the majority of all those
      who were anti-HCV positive were older subjects. Seroepidemiology of hepatitis in
      this well-defined population seems to be different from other parts of Greece, at
      least for hepatitis B and C viruses. There is a very low prevalence of HBsAg and
      a very high incidence of anti-HCV. Low exposure to HAV, as found in other parts
      of the country, was also found in the younger generation in this rural area of
      Crete.

PMID- 9031067
TI  - Risk factors for acute hepatitis B: a case-control study.
AB  - Over the period 1989-1991 a case-control study was carried out in the area of
      Naples comparing 162 subjects with acute hepatitis B and 788 hospitalized control
      subjects. The results of multivariate analysis showed that surgical intervention
      (odds ratio 3.8; 95% CI 1.2-11.7), household contact with an hepatitis B surface
      antigen (HBsAg) positive carrier (odds ratio 2.7; 95% CI 1.1-6.7) and intravenous
      drug use (odds ratio 13.0; 95% CI 3.2-52.7) were risk factors independently
      associated with hepatitis B. No association was found with the other risk factors
      considered, such as blood transfusion, hospitalization, other percutaneous
      exposures, dental therapy, contact with an icteric case, barber shop shaving and
      two or more sexual partners. As a significant proportion of the general
      population undergoes surgical intervention, efficient procedures for
      sterilization of instruments should be implemented, together with the use of
      disposable materials, to control the spread of HBV infection in surgical
      settings.

PMID- 9031068
TI  - Comparison of the Chiron Quantiplex branched DNA (bDNA) assay and the Abbott
      Genostics solution hybridization assay for quantification of hepatitis B viral
      DNA.
AB  - Several assays for quantification of DNA have been developed and are currently
      used in research and clinical laboratories. However, comparison of assay results
      has been difficult owing to the use of different standards and units of
      measurements as well as differences between assays in dynamic range and
      quantification limits. Although a few studies have compared results generated by
      different assays, there has been no consensus on conversion factors and thorough
      analysis has been precluded by small sample size and limited dynamic range
      studied. In this study, we have compared the Chiron branched DNA (bDNA) and
      Abbott liquid hybridization assays for quantification of hepatitis B virus (HBV)
      DNA in clinical specimens and have derived conversion factors to facilitate
      comparison of assay results. Additivity and variance stabilizing (AVAS)
      regression, a form of non-linear regression analysis, was performed on assay
      results for specimens from HBV clinical trials. Our results show that there is a
      strong linear relationship (R2 = 0.96) between log Chiron and log Abbott assay
      results. Conversion factors derived from regression analyses were found to be non
      constant and ranged from 6-40. Analysis of paired assay results below and above
      each assay's limit of quantification (LOQ) indicated that a significantly (P <
      0.01) larger proportion of observations were below the Abbott assay LOQ but above
      the Chiron assay LOQ, indicating that the Chiron assay is significantly more
      sensitive than the Abbott assay. Testing of replicate specimens showed that the
      Chiron assay consistently yielded lower per cent coefficients of variance (% CVs)
      than the Abbott assay, indicating that the Chiron assay provides superior
      precision.

PMID- 9031069
TI  - Clinical aspects, cytogenetics and disease evolution in myelodysplastic
      syndromes.
AB  - Myelodysplastic syndrome (MDS) is a morphologically characterized hematologic
      entity that is one of the clonal myeloproliferative disorders. Approximately 50
      approximately 70% of MDS patients have cytogenetic abnormalities; these are
      usually chromosomal deletions, but some involve translocations such as t(1;7)
      (q10;p10). Translocations involving chromosomal regions 3q26 or 22q11 are often
      therapy-related. Recent studies have demonstrated that cytogenetic changes in MDS
      patients have clinical relevance. Accordingly, there are now scoring systems for
      predicting the prognoses of MDS patients. In this review, we describe the
      clinical significance of cytogenetic changes in MDS. We include MDS with some
      atypical forms, such as MDS with hypocellular bone marrow, MDS with minimal
      dysplasia, and MDS with myelofibrosis.

PMID- 9031070
TI  - TP53 mutations in myelodysplastic syndrome.
AB  - Mutations of the TP53 tumor suppressor gene, contributing to the development and
      progression of a wide variety of human malignancies, are found in some of the
      patients with myelodysplastic syndromes (MDS). Previous reports revealed that
      TP53 mutations were found in 0-25% of patients with MDS and are closely
      associated with a complex abnormal karyotype including such chromosomal losses as
      -5/5q-, -7/7q- and/or 17p-, which are known to be frequent in therapy-related
      leukemias. We have also detected TP53 mutation in 10 (14%) of 70 patients with
      MDS. All of the mutations were detected at the time of diagnosis, which suggest
      the TP53 mutation may play a role in the development of MDS. Those patients with
      a TP53 mutation had a poor prognosis regardless of leukemic transformation or
      not. The reported mutational spectra of TP53 in MDS and ANLL differ from those of
      colon and lung cancers. Compared with other hematological disorders, the spectrum
      of TP53 mutations in MDS and ANLL is assumed to be associated with pathogenic
      exposure to known or unknown carcinogens, as suggested by the chromosomal
      findings. Further studies are required to clarify the pathogenesis of this
      heterogenous disease entity.

PMID- 9031071
TI  - Serum levels of adhesion molecules and cytokines in patients with acute
      leukaemia.
AB  - The cytokine network and the adhesion molecule system are intercellular signal
      pathways. The cytokine effects are modulated in vivo by soluble cytokine
      antagonists, whereas the cell to cell contact mediated by adhesion molecules and
      their ligands may be blocked by the soluble forms of the adhesion molecules. The
      cytokine network is important for proliferation and cytokine secretion by acute
      leukaemia blasts, and membrane-bound adhesion molecules are important for blast
      interactions with neighbouring cells of the in vivo microenvironment. Both these
      signal systems are operative during the period of cytopenia following intensive
      chemotherapy for acute leukaemia. In the present review, we discuss the influence
      of disease status, chemotherapy and complicating infections on serum levels of
      cytokines and soluble adhesion molecules in acute leukaemia patients. We have
      demonstrated increased serum levels of both cytokines and cytokine antagonists in
      acute leukaemia patients with complicating bacterial infections during
      chemotherapy-induced cytopenia. Serum levels of the selectin adhesion molecules
      were decreased during bacterial infections in leukopenic patients compared to
      healthy individuals. In contrast, the intercellular adhesion molecule-1 response
      and the cytokine/cytokine antagonist responses were qualitatively similar to
      responses seen in previously healthy individuals with serious bacterial
      infections.

PMID- 9031072
TI  - Pattern of expression and their clinical implications of the GATA family, stem
      cell leukemia gene, and EVI1 in leukemia and myelodysplastic syndromes.
AB  - Transcription factors play a key role in controlling the cellular differentiation
      of hematopoietic cells. Among the known transcription factors, both GATA-1 and
      SCL play roles in the cellular differentiation of erythrocytic and megakaryocytic
      lineages, while GATA-2 is thought to maintain and promote the proliferation of
      early hematopoietic progenitors. In this review, the clinical implications of
      expression of the GATA family, SCL, and EVI1 gene in various types of human
      leukemia are discussed. De novo acute myeloid leukemia (AML) patients may be
      subdivided into three categories depending on the expression pattern of
      transcription factors, i.e., GATA-1(+)SCL(+), GATA-1(+)SCL(-), and GATA-1(-)SCL(
      ). AML patients with both GATA-1 and SCL expression have a poor prognosis and
      have some characteristic clinical and hematologic features. The EVI1 gene may be
      expressed through at least two pathways in hematologic malignancies; one is
      related to chromosomal changes at 3q26, while the other is related to
      myelodysplasia regardless of chromosomal changes at 3q26 region. These findings
      suggest that the pattern of expression in transcription factors in abnormal
      hematopoietic cells is reflected in the malignant phenotype and play a role in
      the pathogenesis of the disease.

PMID- 9031073
TI  - All-trans-retinoic acid and pseudotumor cerebri.
AB  - Pseudotumor cerebri or idiopathic intracranial hypertension is a neurological
      syndrome characterized by signs and symptoms of intracranial hypertension without
      clinical and radiological evidence of infective or space occupying lesions.
      Iatrogenic factors are frequent; in particular, cases of Pseudotumor cerebri
      associated with all-trans-retinoic acid treatment in acute promyelocytic leukemia
      (APL) have been frequently described in pediatric patients. We review the
      literature and give diagnostic and therapeutic guidelines.

PMID- 9031074
TI  - The role of magnetic resonance imaging in the diagnosis and monitoring of
      myelodysplastic syndromes or leukemia.
AB  - Magnetic resonance imaging (MRI) can provide valuable information about regions
      of the bone marrow which are inaccessible to biopsy. MRI also is unique in
      characterizing normal and abnormal bone marrow because of its ability to
      distinguish fat from other tissues. In patients with myelodysplastic syndromes
      (MDS) or leukemia, marrow MRI is an important tool for accurate diagnosis and
      monitoring and may function as an adjunct to bone marrow aspiration and biopsy.
      In clinical practice, defining the anatomic distribution and extent of marrow
      involvement by MRI is of advantage in the management of patients with MDS or
      leukemia.

PMID- 9031075
TI  - Multidrug resistance in leukemias and its reversal.
AB  - Drug resistance often results in failure of anticancer chemotherapy in leukemias.
      Several mechanisms of drug resistance are known with multidrug resistance (MDR)
      being the best characterized one. MDR can be due to enhanced expression of
      certain genes (MDR1, MRP or LRP), alterations in glutathione-S-transferase
      activity or GSH levels and to reduction of the amount or the activity of
      topoisomerase II. Here we review the current status of the clinical significance
      of the various mechanisms of MDR in leukemias and also discuss possibilities for
      the reversal of MDR. MDR1 gene expression has been seen in many leukemias,
      notably in acute myeloid leukemia (AML) and blast crisis of chronic myeloid
      leukemia. Both MDR1 RNA and P-glycoprotein expression of the leukemic cells have
      been shown to correlate with poor clinical outcome in AML. However, preliminary
      results indicate that the MRP gene as well as the LRP gene can be expressed in
      AML. Thus, drug resistance in leukemias appears to be multifactorial. P
      glycoprotein-mediated MDR can be reversed by several drugs. These resistance
      modifiers are currently evaluated with regard to their clinical efficacy. Despite
      some encouraging results, reversal of drug resistance and subsequent improvement
      in clinical outcome remains to be shown.

PMID- 9031076
TI  - Molecular cytogenetics of t(12;21) (p13;q22).
AB  - The translocation t(12;21)(p13;q22) is a frequent nonrandom rearrangement of B
      cell lineage childhood acute lymphoblastic leukemia (ALL) which fuses the TEL and
      AML1 genes, normally localized to 12p13 and 21q22, respectively. The crucial
      chimeric gene, TEL-AML1, is transcribed from the der(21) and encodes the 336 NH2
      aminoacics of TEL fused to the majority of the AML1 protein. The t(12;21) is very
      often associated with loss of the normal, untranslocated TEL allele. These
      various aspects are presented here.

PMID- 9031077
TI  - Haemopoietic growth factors, the cell cycle of acute myeloblastic leukaemia
      progenitors and sensitivity to cytosine arabinoside.
AB  - We describe an 'in vitro' model which permits assessment of acute myeloblastic
      leukaemia (AML) progenitor cells' response to Ara-C alone and in conjunction with
      recombinant human (rh) cytokines by evaluating cell cycle characteristics of
      purified AML blast progenitors and their chemosensitivity in clonogenic culture
      before and after cytokine priming. Parallel investigation of Ara-C/cytokine
      treatment on normal CFU-GM progenitors was included as these cells are important
      for post-therapeutic reconstitution of haemopoiesis. Kinetic and clonogenic
      findings for AML marrows were extremely variable with G+GM-CSF or IL-3 priming.
      However, inclusion of rhSCF and resultant synergism with the other cytokines,
      introduced a pronounced element of consistency in AML results. Normal CFU-GM
      responded to rhG+GM-CSF or IL-3 with increased kinetic activity and sensitivity
      to Ara-C. rhSCF synergised strongly with the other factors, causing increased
      cell cycling and attainment of maximal chemosensitivity 'in vitro'. No
      correlation was evident between 'in vitro' findings for AML samples, patient FAB
      types or clinical outcome. This study highlights the fact that both normal and
      AML cells can be targeted by rh cytokines, particularly when rhSCF is included in
      priming cocktails.

PMID- 9031078
TI  - BCR/ABL regulation of PI-3 kinase activity.
AB  - The ability of BCR-ABL oncoproteins to induce leukemic transformation of
      hematopoietic cells depends on their tyrosine kinase activity, which is essential
      for recruitment and activation of multiple pathways that transduce oncogenic
      signals. Although it is unknown yet whether activation of PI 3-kinase is required
      for transformation, the colony-forming ability of Philadelphia cells is dependent
      on PI 3-kinase activity, as indicated by the results of studies using a number of
      strategies to interfere with the synthesis and/or the function of the regulatory
      and catalytic subunits of this kinase. In particular, wortmannin, a specific PI 3
      kinase inhibitor, preferentially affected colony formation of Philadelphia cells
      over that of normal marrow hematopoietic progenitors. The mechanism(s) of such
      effects are unknown, but PI 3-kinase inhibitors may represent a novel class of
      therapeutic agents for the ex vivo and/or in vivo treatment of Philadelphia
      leukemias.

PMID- 9031079
TI  - Graft-versus-leukemia effect and its clinical implications.
AB  - Graft-versus-leukemia (GVL) effect is an immunologically important phenomenon
      which decreases the relapse rate of leukemia after allogeneic bone marrow
      transplantation. GVL effect is sometimes associated with the occurrence of graft
      versus-host disease (GVHD). Analyses of GVL effect and GVHD showed that these two
      phenomena were separable in some conditions. Although we cannot yet completely
      control the development of the GVL effect without inducing GVHD in humans, basic
      analyses using animal models show potential benefits of the GVL effect for
      clinical applications. Autologous GVHD is another important phenomenon which can
      help to eradicate minimal residual disease. Interleukin 2 and/or cyclosporin A
      are extensively used in animal models and in humans to induce autologous GVHD,
      showing beneficial effects. In the future, cytokine usage and allogeneic stem
      cell transplantation or leukocyte infusion appear to be promising in the control
      of minimal residual disease. Further studies on the mechanisms of GVL effects and
      GVHD may well open a new era for cell transplantation.

PMID- 9031080
TI  - Leukocyte alkaline phosphatase a specific marker for the post-mitotic
      neutrophilic granulocyte: regulation in acute promyelocytic leukemia.
AB  - Leukocyte alkaline phosphatase (LAP) is the product of the gene coding for the
      liver/bone/kidney-type alkaline phosphatase. In the normal hematopoietic system,
      the only cell type expressing LAP in basal conditions is the post-mitotic
      neutrophilic granulocyte. Thus LAP represents a specific and restrictive marker
      for the terminal maturation of the neutrophilic granulocyte. The study of the
      factors and the molecular mechanisms responsible for the expression of LAP in
      cells undergoing granulocytic maturation may shed light on this complex
      biological process. Acute promyelocytic leukemia (APL) represents a unique
      biological model in which it is possible to investigate neutrophilic
      differentiation. APL blasts undergo rapid and irreversible maturation towards
      cells morphologically and biochemically resembling normal mature granulocytes
      upon in vivo and in vitro challenge with all-trans retinoic acid (ATRA). In this
      cellular context, we studied the endogenous factors involved in the expression of
      LAP. The phosphatase is not synthesized in undifferentiated APL blasts and it is
      expressed only upon treatment with combinations between ATRA and a second cyto
      differentiating signal. The second signal may be given by G-CSF, cAMP analogs, IL
      6 and to a lesser extent by IL-1 beta. The molecular mechanisms underlying the
      induction of LAP by combinations of ATRA and G-CSF or cAMP analogs were studied
      in detail and are the object of this review.

PMID- 9031081
TI  - Role of the cyclin-dependent kinase 4 and 6 inhibitor gene family p15, p16, p18
      and p19 in leukemia and lymphoma.
AB  - Neoplastic diseases are proliferative disorders characterized by uncoordinated
      cell growth. Cellular proliferation follows an orderly progression through the
      cell cycle, which is governed by different cyclins and cyclin dependent kinases
      (CDKs). Recently, CDK-inhibitors, which are a new class of small proteins
      involved in the negative regulation of the cell cycle, have been identified by
      virtue of their ability to interact physically with cyclin/CDK-complexes. As the
      genes encoding the CDK4- and CDK6-inhibitors (CDK4/6-inhibitors)
      p16INK4A/CDKN2/MTS1 and p15INK4B/MTS2 have been found to be altered in many
      cancer cell lines and primary neoplastic tissues, CDK-inhibitors in general and
      CDK4/6-inhibitors in particular are now a se: of candidate tumor suppressors. The
      p15 and p16 genes map to a region frequently deleted in lymphoid neoplasms.
      Therefore, considerable efforts have been made to determine the role of CDK4/6
      inhibitors in hematologic malignancies: This article will review alterations of
      components of the cell-cycle machinery in brief and summarize the role of the
      CDK4/6-inhibitors p16INK4A, p15INK4B, p18INK4C and p19INK4D in leukemias and
      lymphomas.

PMID- 9031082
TI  - Fas antigen/APO-1 (CD95) expression on myeloma cells.
AB  - Many factors involved in the proliferation of myelomas have been reported, and
      the relationship between these factors and the pathogenesis of multiple myeloma
      has been discussed. We found that most myeloma cells express Fas antigen/APO-1
      (CD95), a cell surface antigen that mediates apoptosis. However only some cells
      are sensitive to anti-Fas antibody and undergo apoptosis. These data indicate
      that some multiple myelomas are generated not only by cell proliferation but also
      by cell immortalization. The mechanism by which myelomas are immortalized is
      still unclear, but Bcl-2, Bcl-xL, adult T cell leukemia derived factor (ADF),
      soluble Fas are all candidate factors for this mechanism. The possibility also
      exists that inducers of apoptosis, e.g. tumor necrosis factor(TNF), interleukin-1
      beta-converting enzyme(ICE), Bcl-xS, or Bax, do not have a lethal effect. In this
      review, we focus on the system that immortalizes myeloma cells, and suggest the
      possibility that multiple myeloma constitutes one group of cells which cannot
      undergo apoptosis in the bone marrow.

PMID- 9031083
TI  - The effects of thrombopoietin on the growth of acute myeloblastic leukemia cells.
AB  - Thrombopoietin (TPO) is a novel hematopoietic growth factor that was cloned as a
      ligand for c-mpl proto-oncogene. The c-mpl proto-oncogene is expressed on various
      types of human leukemia cell lines derived from erythroid, megakaryocytic, and
      stem-cell leukemia cells. Also, c-mpl mRNA is detectable on blast cells in about
      half of acute myeloblastic leukemia (AML) cases regardless of French-American
      British (FAB) classification. In the cases with myelodysplastic syndrome, c-mpl
      is expressed in a substantial fraction of refractory anemia with excess of blast
      (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia cells, but
      not in refractory anemia or sideroblastic anemia. Little or no expression of c
      mpl mRNA is observed in human lymphoid cell lines and blast cells of acute
      lymphoblastic leukemia cases. The in vitro treatment of AML cells with TPO
      resulted in proliferation in about 70% of c-mpl-positive AML cases. The
      proliferative responses of AML cells to TPO were observed not only in M7-type,
      but also in the other subtypes of AML cases. Furthermore, the TPO-induced
      proliferation of AML cells was augmented by the addition of the other
      hematopoietic growth factors such as interleukin-3 (IL-3), IL-6, stem cell
      factor, or granulocyte-macrophage colony-stimulating factor. In addition to
      proliferation, TPO appeared to induce megakaryocytic differentiation in a small
      part of AML cells. These results suggested that TPO/c-mpl system might
      contribute, at least in part, to abnormal growth and differentiation of AML
      cells.

PMID- 9031084
TI  - Clinical relevance of all-trans retinoic acid pharmacokinetics and its modulation
      in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is uniquely sensitive to treatment with all
      trans retinoic acid (ATRA) which exerts its action via a well-documented
      cytodifferentiating mechanism. The combination of this retinoid with
      anthracyclines gives high percentages of complete remission and is now considered
      the optimal induction treatment for APL patients. Continuous treatment with ATRA,
      however, induces accelerated drug catabolism, with progressive decline in plasma
      drug concentrations potentially to below the levels required to maintain
      differentiation of leukemic cells. This process, which occurs rapidly and
      consistently has led to the hypothesis that the development of acquired clinical
      resistance to ATRA in APL has a pharmacologic basis. The rapid autoinduction of
      the hypercatabolic state precludes maintenance with continuous ATRA oral dosing,
      and is a limitation of better use of the drug both in APL and in other disorders
      in which it could be beneficial. Here we briefly review the pharmacologic
      alterations of ATRA metabolism induced by continuous oral administration, the
      clinical implications of this phenomenon, and the strategies currently under
      investigation to prevent or overcome the induced catabolism of this retinoid.

PMID- 9031085
TI  - Expression of erythroid-specific genes in megakaryoblastic disorders.
AB  - Currently available data indicate that erythroid and megakaryocytic
      differentiation pathways are closely related to each other, and there may exist
      progenitor cells common to those two lineages may exist. Acute megakaryoblastic
      leukemia (AML-M7) and transient myeloproliferative disorder in Down's syndrome
      (TMD) are characterized by rapid growth of abnormal blast cells which express
      megakaryocytic markers. These blast cells express lineage-specific transcription
      factors such as GATA-1 common to these lineages and frequently express erythroid
      specific mRNAs such as gamma-globin and erythroid delta-aminolevulinate synthase
      (ALAS-E), indicating that most of the blasts in M7 and TMD cases have erythroid
      and megakaryocytic phenotypes. These results suggest that blasts in M7 and TMD
      may correspond to progenitors of both erythroid and megakaryocytic lineages.

PMID- 9031086
TI  - The human immunodeficiency virus type-1 (HIV-1) Tat protein and Bcl-2 gene
      expression.
AB  - Tat protein of human immunodeficiency virus type-1 (HIV-1) plays a central role
      in viral replication and shows pleiotropic effects on the survival and growth of
      different cell types. Remarkably, Tat represents the first example of a viral
      protein, that can also be actively secreted by infected cells and shows a
      cytokine-like activity on both HIV-1 infected and uninfected cells. We previously
      reported that the stable expression of tat cDNA rescues Jurkat cell lines from
      apoptosis induced by a variety of stimuli, such as serum withdrawal, engagement
      of fas antigen or even a productive infection with HIV-1. These findings
      suggested that Tat was able to modulate the expression of one or more gene(s)
      relevant for the control of cell survival/death. Consistently, Jurkat cells
      stably transfected with tat show an upregulated expression of bcl-2. It is still
      unsettled whether Tat affects cell survival and bcl-2 expression directly or
      indirectly, modulating the expression of other cellular genes involved in the
      control of cell survival or encoding for cytokines. Blocking experiments
      performed with anti-Tat neutralizing antibodies revealed that TAt increases bcl-2
      expression and prevent lymphoid T cells from apoptosis by acting, at least in
      part, through an autocrine/paracrine loop. While high (nM-microM) concentrations
      of extracellular Tat display a cytotoxic activity on the antigen-mediated
      induction of T cell proliferation, low (pM) concentrations of Tat were able to
      protect both Jurkat cells and primary peripheral blood mononuclear cells from
      apoptosis. Significantly, pM concentrations of Tat were detected in the sera of
      some HIV-1 infected individuals as well as in the culture supernatant of HIV-1
      infected cells, raising the possibility that these levels of Tat protein may be
      present physiologically in vivo. The potential relevance of Tat-mediated
      upregulation of bcl-2 for the pathogenesis of HIV-1 disease is discussed.

PMID- 9031087
TI  - Clinical and laboratory features of adult T-cell leukaemia lymphoma in Barbados.
AB  - We describe the clinical and pathological features of 23 Afro-Caribbean patients
      with adult T-cell leukaemia/lymphoma admitted to the Queen Elizabeth Hospital,
      Barbados over a 5 year period. There were 9 males and 14 females, with a median
      age of 38 years (range 14-84). Twelve had acute leukaemia, 10 lymphoma (including
      4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had
      a past history of tropical spastic paraparesis/HTLV I associated myelopathy
      (TSP/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy
      (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar
      to the disease in the other Caribbean islands and Japan, except that in Barbados
      the age of onset is over a decade younger than in Japan.

PMID- 9031088
TI  - Multifactorial drug-resistance phenomenon in acute leukemias: impact of P170
      MDR1, LRP56 protein, glutathione-transferases and metallothionein systems on
      clinical outcome.
AB  - The multidrug resistance phenomenon can be observed in cases which do not express
      the P170 protein and these cases are suspected as having activated different
      resistance phenomena. Four phenomena were studied at the time of diagnosis in a
      series of 35 lymphoblastic and 25 myeloblastic acute (de novo) leukemias, by an
      immunocytochemical method. Two energetic drug transport processes were
      investigated: the classical MDR/P170 and the P110/LRP56 proteins, and two
      physiological detoxifying activities such as the glutathione transferases (GST
      alpha, mu, pi) and the metallothioneins (Mts). The results demonstrate that these
      phenomena are independent but their synergic activity can increase their impact
      on the outcome. P110/LRP56 positive cases demonstrated 48.8% complete remission
      (CR) rate compared to 71.4% for negative tests. When P170 and P110 were both
      positive or negative, the CR rates were 27.3% and 81.8% respectively (p =
      0.0120), and survival curves were also different (p = 0.030). The CR rate in AML
      or ALL is weakly affected by GST pi, alpha or mu but relapses are more frequently
      observed for Positive-GST pi ALL (p = 0.0658). Patients with both P170 and GST pi
      positive reactions had a 53.3% CR rate compared to 78.9% for both negative
      reactions. Survival curves for these two groups were different. The CR rate in
      AMl was 100% for Mts positive and 43.7% for negative cases (p = 0.050), however
      the median survival was totally different for these two groups (p = 0.046). CR
      rates were 26.6% for patients who were P170 positive and Mts negative compared to
      100% for P170 negative and Mts positive (p = 0.038) patients. Survival curves
      were also different (p = 0.0510). We conclude that these four mechanisms induce
      an independent drug resistance but their synergic action increase their impact on
      the outcome. The metallothioneins seem to have a major impact on the drug
      resistance phenomenon and its effect should be investigated with high priority,
      in the light of these results.

PMID- 9031089
TI  - Adult lymphoblastic lymphoma: clinical features and prognostic factors in 53
      patients.
AB  - Lymphoblastic lymphoma (LBL) in adult patients is recognized as a particular
      entity in the high-grade non-Hodgkin's lymphoma (HG-NHL) group with
      characteristic clinical and prognostic features. Initially, polychemotherapy
      normally used in HG-NHL failed to produce long-term relapse-free survival because
      of progression disease in the CNS and in the bone marrow. Subsequently, the
      intensification of therapy using multimodality aggressive acute lymphoblastic
      leukemia (ALL) treatments led to an increase in long-term relapse-free survival.
      We analyzed retrospectively 53 adult patients with LBL according to the Kiel
      classification and the criteria by Nathwani et al. Therapeutic modifications
      depended upon the different times of diagnosis. Twenty-one patients received the
      modified L17 regimen, 13 patients were treated with the L0288 regimen, and 19
      patients were submitted to the L20 protocol. There was no significant differences
      in CR rates among the three protocols: 48% vs 54% vs 63%, respectively. Nineteen
      of 29 patients who achieved CR were alive and relapse-free at a median follow-up
      of 84 months. Ten of the CR patients underwent autologous bone marrow
      transplantation (ABMT) to consolidate the first response and 7 of them are alive
      and relapse-free. Early stage of disease, age < 30 years, low LDH levels, the
      absence of leukemic phase at diagnosis, and, in particular the attainment of CR
      were all features of patients with good prognosis. Our study confirms the role of
      intensive polychemotherapeutic regimens including CNS prophylaxis, the
      significance of a score model of prognostic factors, and of the role of ABMT (or
      allogeneic bone marrow transplantation) in the treatment of adult LBL.

PMID- 9031090
TI  - Nuclear NF-ATp is a hallmark of unstimulated B cells from B-CLL patients.
AB  - B lymphocytes from the peripheral blood of patients with chronic lymphocytic
      leukaemia (CLL) were analysed for the nuclear presence and DNA binding of a panel
      of transcription factors which are involved in the gene control of lymphoid
      cells. The following transcription factors were studied: the Octamer factors Oct
      1 and Oct-2, members of the AP-1 factor family, NF-AT factors, in particular NF
      ATp, and members of the Rel/NF-kB family. We show that the constitutive nuclear
      translocation of NF-ATp, a member of the growing family of NF-AT factors, is a
      hallmark of nonstimulated B cells from CLL patients that distinguishes B-CLL
      cells from 'normal' B lymphocytes. Constitutive nuclear appearance was also
      observed for NF-kB2/p52. Constitutive binding of further factor proteins to DNA,
      such as JunD, c-Fos and FosB, was detected in several patients whereas the
      localisation and DNA binding of other factors such as c-Jun, RelA/p65 and c-Rel
      was unaltered. It is remarkable that in B-CLL cells the nuclear appearance and
      DNA binding of specific transcription factors is dramatically affected whereas
      other members of the same factor family remained unaltered in these leukemic
      cells. It remains to be shown which molecular events lead to the specific 'pre
      activation', i.e. constitutive nuclear translocation and DNA binding, of these
      members of NF-AT, NF-kB and AP-1 factor families.

PMID- 9031091
TI  - Nasal T/NK cell lymphoma: a clinico pathologic study of 30 west Chinese patients
      with special reference to proliferation and apoptosis.
AB  - Midfacial T-cell lymphomas are more prevalent in Asia than in Europe or North
      America. Clinically, these lymphomas are noted as one major differential
      diagnosis in the malignant midline granuloma syndrome. During the past years, the
      group of nasal T/NK cell lymphomas has been recognized that is frequently
      associated with EBV-infection. The aim of the current publication was to describe
      the clinical presentation and course of 30 patients attending the West China
      University of Medical Sciences, Chengdu, P.R. China, between 1991 and 1994.
      Clinical records were assessed and the patients were followed for 6 to 29 (mean
      12.4) months. Several microscopic features thought to be associated with this
      entity were carefully evaluated together with immunohistochemical data. The
      proliferation of the tumour cells was assessed by determining the mitotic index
      and the ratio of MIB-1 labelled cells. In addition, the incidence of apoptotic
      cells was investigated by means of the in-situ end labelling (ISEL) technique.
      Our data confirm the expression of T-cell markers by T/NK cell lymphomas as
      determined by the immunohistochemistry. The apoptotic index was found to
      correlate with the ratio of MIB-1 labelled cells. Expression of the bcl-2
      oncoprotein was not associated with increased or diminished proliferation or cell
      death, respectively. Eight of the thirty patients succumbed to their disease
      during the follow-up period. Kaplan-Meier cumulative survivals and log-rank tests
      revealed a significant impact of MIB-1 labelling on mean survival times.

PMID- 9031092
TI  - Fluorescent in situ hybridization (FISH) for the detection of trisomy 8 in acute
      myeloblastic leukemia.
AB  - The karyotype of acute myeloid leukemia (AML) blasts has a major prognostic
      importance. However conventional cytogenetic studies of AML patients may fail to
      reveal chromosome abnormalities. Trisomy 8 is a common numerical abnormality in
      all AML subtypes. We evaluated the role of fluorescent in situ hybridization
      (FISH) in the detection of trisomy 8 in de-novo AML, and compared the results to
      chromosome analysis in some patients. Cytogenetic studies were performed in 9 of
      12 patients. In three patients no metaphases were obtained. Of the remaining six,
      trisomy 8 was only detected in the metaphases of 1 patient. In contrast, 4
      patients showed +8 with FISH and one had a borderline value. We conclude that
      FISH is a rapid and sensitive method to detect numerical aberrations in AML. In
      the future larger prospective studies should explore the biological and clinical
      application of the FISH method in different hematological malignancies.

PMID- 9031094
TI  - Endocrine characterization of primary mediastinal lymphoma.
AB  - Because of the characteristic presentation of primary mediastinal large cell
      lymphoma (PMLCL) in young females its known origin from thymic B-cells, there
      might be a role in lymphomagenesis for estrogen receptors as well as for known
      neuroendocrine thymic mediators. A retrospective review of all patients with
      diffuse large cell lymphoma seen at our institution from January 1985 to January
      1994 revealed 75 consecutive cases with a diagnosis of PMLCL. Through retrieval
      from our pathologic archives and requests to outside pathologists, we recovered
      and analyzed 17 biopsy specimens for the presence of the following hormone
      receptors: estrogen, beta endorphin, prolactin, T3, growth hormone, and
      leutinizing hormone. None of the specimens stained for any of the reagents. The
      most plausible explanation is that PMLCL tissues are devoid of these hormonal
      receptors and thus these receptors do not seem to play a role in the pathogenesis
      of PMLCL.

PMID- 9031093
TI  - Incidence and characteristics of lymphoid malignancies in untreated
      myelodysplastic syndromes.
AB  - We have analyzed 1,198 patients with untreated myelodysplastic syndromes (MDS)
      with two main objectives: (1) to determine the prevalence of lymphoid
      malignancies (LM) in MDS patients; and (2) to ascertain whether there is some
      relationship between the MDS subtype and the LM type. In fourteen of 1,198
      primary MDS patients (1%) (4 with refractory anemia, 3 with refractory anemia
      with ring sideroblasts, 2 with refractory anemia with excess of blasts and 5 with
      chronic myelomonocytic leukemia) a LM was detected. In all cases, the LM was of
      the B-cell type: 6 cases of chronic lymphocytic leukemia, 5 cases of
      lymphoplasmacytoid lymphoma, and 3 cases of multiple myeloma. B-cell malignancy
      did not prevail in any MDS subtype and no correlation was observed between the
      different varieties of both diseases. In conclusion, in this large series, 1% of
      the untreated patients with MDS had B-cell malignancy, an association that in
      most cases is likely to be merely coincidental.

PMID- 9031095
TI  - Occurrence of myeloma in a chronic lymphocytic leukemia patients after response
      to differentiation therapy with interleukin-4.
AB  - The occurrence of chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in
      a single individual is rare, and the clonal relationship between the two
      neoplasms is unclear. We describe here a patient with CLL who developed symptoms
      of MM while responding to experimental therapy with interleukin-4 (IL-4). This
      patient was treated with 2-chlorodeoxyadenosine (2-CDA), and had a response in
      both malignancies.

PMID- 9031096
TI  - Non-pyothorax-associated primary pleural lymphoma with complex karyotypic
      abnormalities.
AB  - We describe a case of non-pyothorax-associated primary pleural lymphoma with bone
      marrow and central nervous system involvement, and complex karyotypic
      abnormalities involving nullisomy chromosome 17 and multiple breakpoints that are
      commonly associated with acute leukemia and myeloproliferative diseases.

PMID- 9031097
TI  - Unexpected synchronous non-Hodgkin's lymphoma encountered during the treatment of
      a previously-diagnosed carcinoma: report of three cases.
AB  - We report three patients in whom non-Hodgkin's lymphomas (NHL) were unexpectedly
      found during treatment of previously-diagnosed carcinoma. The first patient was a
      72 year old woman with an endometrioid carcinoma in whom NHL was found in the
      pelvic lymph nodes. The second patient was a 76 year-old man with adenocarcinoma
      of the stomach and NHL of the small intestine. The third patient was a 66 year
      old man with adenocarcinoma of the prostate and NHL of the iliac lymph nodes. In
      these patients, it was necessary to exclude metastasis of the known carcinoma and
      to establish the diagnosis of unexpected NHL. The adjuvant treatment plans of the
      patients were ultimately not significantly altered, but increased surveillance
      for recurrence of two neoplasms is now warranted. These patients altered us to
      beware of indolent NHL in specimens removed for the treatment of carcinoma.

PMID- 9031098
TI  - An unusual case of a splenic gamma/delta T-cell lymphoma with angiocentric
      tendency and haemophagocytic syndrome.
AB  - We report here an unusual post-thymic T-cell neoplasia of the spleen associated
      with a rapidly progressive haemophagocytic syndrome. The lymphoma was classified
      as a medium- to large sized pleomorphic T-cell lymphoma with angiocentric
      tendency (CD3+, CD43+, CD45RO+ CD45+). Clonality was confirmed by PCR and
      revealed rearrangement of the T-cell receptor gamma chain. Serological tests
      excluded a recent EBV infection and in situ hybridization with the EBER probe was
      negative. Haemophagocytic syndrome was the initial finding in an otherwise
      symptomless patient and this deteriorated with progression of the T-cell
      malignancy. Both, the T-cell lymphoma and the haemophagocytic syndrome remained
      unaffected by chemotherapy. Splenic gamma/delta T-cell lymphoma associated with
      haemophagocytosis is an uncommon entity which has until now not been widely
      recognized.

PMID- 9031099
TI  - Chlorambucil in chronic lymphocytic leukemia: mechanism of action.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western
      countries but the clinical presentation and rate of disease progression are
      highly variable. When treatment is required the most commonly used therapy is the
      nitrogen mustard alkylating agent, chlorambucil (CLB), with or without
      prednisone. Although CLB has been used in the treatment of CLL for forty years
      the exact mechanism of action of this agent in CLL is still unclear. Studies in
      proliferating model tumor systems have demonstrated that CLB can bind to a
      variety of cellular structures such as membranes, RNA, proteins and DNA; however,
      DNA crosslinking appears to be most important for antitumor activity in these
      systems. In addition, a number of different mechanisms can contribute to CLB
      resistance in these tumor models including increased drug metabolism, DNA repair
      and CLB detoxification resulting from elevated levels of glutathione (GSH) and
      glutathione S-transferase (GST) activity. However, unlike tumor models in vitro,
      CLL cells are generally not proliferating and studies in CLL cells have raised
      questions about the hypothesis that DNA crosslinking is the major mechanism of
      antitumor action for CLB in this disease. CLB induces apoptosis in CLL cells and
      this appears to correlate with the clinical effects of this agent. Thus,
      alkylation of cellular targets other than DNA, which can also induce apoptosis,
      may contribute to the activity of CLB. Alterations in genes such as p53, mdm-2,
      bcl-2 and bax which control entry into apoptosis may cause drug resistance. Loss
      of wild-type p53 by mutation or deletion occurs in 10 to 15% of CLL patients and
      appears to correlate strongly with poor clinical response to CLB. The induction
      of apoptosis by CLB is paralleled by an increase in P53 and Mdm-2 but this
      increase in not observed in patients with p53 mutations indicating that with high
      drug concentrations CLB can produce cell death through P53 independent pathways.
      The level of Mdm-2 mRNA in the CLL cells is not a useful predictor of drug
      sensitivity. In addition, although Bax and Bcl-2 are important regulators of
      apoptosis and the levels of these proteins are elevated in CLL cells compared
      with normal B cells, the levels of Bax and Bcl-2, or the Bax:Bcl-2 ratio, are not
      important determinants of drug sensitivity in this leukemia. Finally, whereas CLB
      and nucleoside analogs may produce cell death in CLL by a P53 dependent pathway
      other agents, such as dexamethasone or vincristine, may act through P53
      independent pathways.

PMID- 9031100
TI  - Autologous transplantation with tumor-free graft: a model for multiple myeloma
      patients.
AB  - The importance of obtaining a tumor-free graft for autologous transplantation in
      cancer patients has been debated extensively in the last decade and is still
      unresolved largely because it is believed that relapse is more likely to
      originate from the host and not from the graft. This is in spite of recent
      indications that the main source of relapse is the graft. In this review article
      we bring forward evidence that the currently used grafts, whether from peripheral
      blood or bone marrow, harbour significant number of tumor cells before and even
      after purging with currently available purging protocols. We believe that the use
      of a tumor-free graft is the only way to obtain a valid assessment of the
      efficacy of high dose radio-chemotherapy, and is the only methodology to increase
      the probability to achieve long term survival following AT. Accordingly, we
      describe in detail a procedure to obtain a tumor-free graft, designed for the
      treatment of multiple myeloma patients based on flow-sorting of CD34+ stem cells.

PMID- 9031101
TI  - Adoptive immunotherapy for Epstein-Barr virus-related lymphoma.
AB  - Epstein-Barr virus (EBV) causes opportunistic B cell lymphomas in patients whose
      cellular immunity is compromised. We have been investigating whether infusions of
      donor-derived, EBV-specific cytotoxic T cells can prevent and/or treat EBV
      related lymphoproliferative disease in children receiving T cell-depleted bone
      marrow from HLA-matched, unrelated or HLA-mismatched, related donors. In this
      review, we discuss the rationale for this therapeutic approach, describe our
      experiences with the regimen thus far, and consider some future directions in
      immunotherapy.

PMID- 9031102
TI  - Unrelated donor bone marrow transplantation for hematological malignancies
      current status.
AB  - We have explored the efficacy and toxicity of hematopoietic stem cell
      transplantation from unrelated donors for hematologic malignancies and other
      disorders. While most marrow donors have been identified through the National
      Marrow Donor Program in cooperation with many international registries, the
      recent development of unrelated donor umbilical cord blood (UCB) banks has
      allowed us to also evaluate this stem cell source. Analysis of the first 211 URD
      BMT performed at the University of Minnesota shows an overall survival of 33%,
      with older recipient age and transplant from a donor with a major HLA-A or B
      mismatch independently associated with poorer survival. Analysis of engraftment
      of URD marrow shows increasing risk of delayed or incomplete engraftment with
      increasing HLA disparity between URD and recipient. GVHD is increased in
      recipients of URD marrow compared with recipients of related donor marrow.
      Malignant relapse, however, is less frequent in URD marrow recipients, perhaps
      due to an increased graft-versus-leukemia effect. Formal assessment shows quality
      of life in long term URD BMT survivors (beyond 2 years) is excellent, and not
      different from that seen in sibling marrow recipients. Data from patients
      receiving unrelated donor UCB transplantation at the University of Minnesota
      indicate that UCB is an acceptable alternate source of stem cells, at least for
      young recipients, and may be associated with a reduced incidence of GVHD. Ongoing
      studies at the University of Minnesota include examination of the applicability
      of unrelated UCB transplantation to adult recipients, and of the degree of HLA
      incompatibility which can be tolerated in UCB transplantation. Studies to
      identify the optimal GVHD prophylaxis for URD BMT, and to examine the role of
      class II matching in transplant outcome are in progress.

PMID- 9031104
TI  - Inactivation of the p15INK4B and p16INK4 genes in hematologic malignancies.
AB  - The recently discovered p15INK4B and p16INK4 genes encoding cell cycle regulating
      proteins, map to a region on chromosome 9p21 that is commonly deleted in a
      variety of malignant diseases. The p16INK4 gene has now been shown to be a tumor
      suppressor gene. It is frequently inactivated in cancer and is possibly the
      second most often mutated gene in human malignant disease after p53. The role of
      the p15INK4B and p16INK4 genes in hematologic malignancies has been the subject
      of intense investigation since their discovery. In this review we address the
      function and possible role in tumorigenesis of the p15INK4B and p16INK4 genes and
      discuss their significance as prognostic markers in hematologic malignancies.

PMID- 9031103
TI  - Acute myeloid leukemia with translocation (8;21). Cytomorphology, dysplasia and
      prognostic factors in 41 cases. AML Cooperative Group and ECOG.
AB  - The translocation t(8;21) is one of the most common structural aberrations in
      acute myeloid leukemia (AML). Excellent response rates and a better relapse-free
      survival have been described. We analyzed specific morphologic and cytochemical
      features including dysplasia and other prognostic factors in 41 patients with AML
      and t(8;21) who underwent aggressive chemotherapy in two national cooperative
      group studies. Five patients were classified as AML M1 and 36 as AML M2 according
      to the FAB criteria. Auer rods were detected in 28 patients (68%), however in
      only 16 patients were they "thin and elongated" as has been described as typical
      for t(8;21). The presence or absence of Auer rods did not appear to be associated
      with disease-free survival in this sample. Dysgranulopoiesis was detected in
      31/41 patients (90%); five of these patients additionally had dyserythropoiesis
      (12%). In six cases (15%), dysmegakaryopoiesis was seen in combination with
      dysgranulopoiesis. Only one patient had trilineage dysplasia. Dysplastic features
      had no influence on prognosis. Additional cytogenetic abnormalities were detected
      in 24/41 patients. Twelve male (48%) and four female (25%) had a loss of a sex
      chromosome. This was correlated with a better disease-free survival (p = 0.039).
      The complete remission rate (CR) to chemotherapy was 90%. The early death rate
      was 10%. Disease-free survival of the complete responders was 60% at two years
      with no relapses observed in ten patients with 2-6 years of follow up. This
      favorable disease-free survival was observed with a variety of post-induction
      regimens and t(8;21) had been detected as an independent factor for good
      prognosis. The need for very intensive therapy, such as bone marrow
      transplantation, is unanswered at this time.

PMID- 9031105
TI  - Practical guidelines for the management of chronic myelogenous leukemia with
      interferon alpha.
AB  - Interferon-A (IFN-A) is an effective agent in the treatment of chronic
      myelogenous leukemia (CML). Hematologic remissions occur in the majority of
      patients with newly diagnosed disease, and cytogenetic remissions may occur in up
      to 50% of patients. Several studies have shown a correlation between the dose of
      IFN-A and achievement of a major cytogenetic response; this response has also
      been correlated with prolonged survival. However, IFN-A may be associated with
      significant side effects that reduce enthusiasm for the use of this drug, produce
      difficulties in patient compliance, and limit the dose delivered to the patient,
      thus resulting in ineffective use of IFN-A. Experience with this drug has led to
      a refinement in techniques for initiation of therapy as well as interventions to
      deal with side effects. These strategies are often not discussed in publications
      dealing with response rates and survival. In this review we discuss strategies to
      minimize toxicity and improve the effectiveness of IFN-A in the treatment of CML.

PMID- 9031106
TI  - Diagnostic and prognostic significance of cytogenetics in adult primary
      myelodysplastic syndromes.
AB  - Cytogenetic analysis has proven to be a mandatory part of the diagnosis of
      myelodysplastic syndromes (MDS) as well as a major indicator for predicting
      clinical course and outcome. This review concentrates on the cytogenetic
      classifications, the incidence and types of chromosome defects and the prognostic
      significance of the karyotype in adult primary MDS. Two cytogenetic
      classifications are currently used: one is based on the karyotype complexity
      (normal, single, double or complex defects), the other on clonal status (all
      metaphases normal, abnormal or admixture of normal and abnormal clones).
      Chromosome abnormalities are of both numerical and structural types. Aside from
      the 5q-syndrome, no specific clinico-cytogenetic entity has been reported.
      However, several distinct clinical and cellular features have been identified
      that correlate with the presence of specific chromosome defects such as
      inv(3)/t(3;3), +6, t(5;12), del(17p) and del(20q). The presence of complex
      defects is associated with reduced survival and a high risk of leukemic
      transformation. Among single defects, specific abnormalities may define distinct
      prognostic groups. Patients with del(5q) as a sole chromosome defect and a
      refractory anemia without excess of blasts have a favourable prognosis. For
      patients with trisomy 8 or monosomy 7 there may be distinct types of clinical
      evolution. Most patients with the 3q21q26 syndrome have a short survival. The
      presence of two chromosome defects may constitute an independent cytogenetic
      entity probably associated with relative poor prognosis. Karyotypic evolution
      generally represents a poor risk factor. The combination of cytogenetics with
      clinical and hematological features has proven to provide for a better prediction
      of patients' survival, leukemic transformation and response to treatment. Several
      scoring systems have been developed. They have to be improved by the study of new
      patients according to strict clinical and cytogenetic criteria and by the
      addition of newly recognized prognostic indicators such as histopathological
      features and molecular genetic mutations.

PMID- 9031107
TI  - Granulocyte dysplasia and dysfunction, and CD11/CD18 defects in myelodysplastic
      syndromes.
AB  - In myelodysplastic syndromes (MDS), dysplastic changes in neutrophils are a
      common feature reflecting the total degree of bone marrow dysplasia. Furthermore,
      granulocyte function is abnormal, so that a high risk of life-threatening
      infections has been documented. In this review we shall focus on the defects of
      both granulocytes and their CD11b/CD18 glycoprotein complex, which regulate
      granulocyte adherence, locomotion, diapedesis and migration into inflammatory
      sites, in patients suffering from primary MDS. The defective surface membrane
      glycoprotein expression of myelodysplastic phagocytes is not only a useful
      diagnostic tool, but also a powerful prognostic one, since MDS patients with such
      defects present both an increased susceptibility to infections and a decreased
      survival. Moreover, the administration of colony-stimulating factors is known to
      be able to elicit long-lasting improvement in neutrophil count, CD11b/CD18
      expression and function, marrow myeloid maturation, and possibly to decrease
      bacterial infections in MDS patients.

PMID- 9031108
TI  - The biologic function of PML and its role in acute promyelocytic leukemia.
AB  - Patients with acute promyelocytic leukemia (APL) are characterized by the
      presence of a t(15;17) chromosomal translocation. The fusion protein PML-RAR
      alpha encoded from the breakpoint can form a heterodimer and acts as a dominant
      negative inhibitor against the normal function of PML. Recently we demonstrated
      that PML is a growth suppressor and transcription suppressor expressed in all
      cell lines tested. We also found that PML suppresses the clonogenicity and
      tumorigenicity of APL-derived NB4 cells, as well as the transformation of rat
      embryo fibroblasts by cooperative oncogenes and NIH/3T3 by neu. Overexpression of
      PML in human tumor cell lines induces a remarkable reduction in growth rate in
      vitro and in vivo. More recently, we have shown that PML is a phosphoprotein
      associated with the nuclear matrix and that its expression is cell cycle related.
      PML expression is altered during human oncogenesis, implying that PML may be an
      anti-oncogene involved not only in APL but also in other oncogenic events.
      Mutation analysis of the functional domains of PML demonstrated that its ability
      to form PML nuclear bodies or PODs (PML oncogenic domains) is essential for
      suppressing growth and transformation. In light of the above studies it appears
      that disruption of the normal function of PML plays a critical role in the
      pathogenesis of APL.

PMID- 9031109
TI  - ETV6 gene rearrangements in hematopoietic malignant disorders.
AB  - Chromosomal abnormalities involving the short arm of chromosome 12 have been
      frequently observed in a broad spectrum of hematological malignancies. Recently,
      a gene located in this chromosomal region and implicated in leukemogenesis was
      identified. The gene, called ETV6 (previously known as TEL) is a new member of
      the ETS family, a group of genes thought to act as transcriptional activators.
      The gene spans 240 kb and consists of eight exons coding for a helix-loop-helix
      (HLH) and a DNA-binding domain. ETV6 was originally identified in a
      t(5;12)(q33;p13) occurring in a chronic myelomonocytic leukemia (CMML). Recent
      reports, however, show its involvement in a growing number of translocations
      associated with myeloid as well as lymphoid leukemias. At the molecular level
      fusions of ETV6 with PDGFRB (5q33), ABL (9q34), MNI(22q11) and AML1(21q22) have
      already been identified. Analysis of these chimeric proteins indicates that
      distinct domains of ETV6 can be involved in different fusion products, thus ETV6
      can provide transcriptional and dimerization properties for partner genes, or the
      gene itself can act as an altered transcriptional factor. At least two clinico
      pathological entities associated with ETV6 rearrangements have emerged as
      distinct disorders. The first one is a chronic myeloid malignancy characterized
      by t(5;12)(q33;p13), monocytosis and/or eosinophilia. The second entity is a type
      of childhood acute lymphoblastic leukemia (ALL) hallmarked by t(12;21)(p13;q22),
      and is shown to be the most frequent but cytogenetically largely undetectable
      chromosomal anomaly in childhood ALL.

PMID- 9031110
TI  - Role of hepatocyte growth factor in hemopoiesis.
AB  - Hepatocyte growth factor (HGF) is a polypeptide that stimulates proliferation,
      motility, and morphogenesis of various cells, particularly epithelial cells.
      There is considerable evidence that HGF is a regulator in hemopoiesis not only in
      mice but also in humans. In mice, HGF and c-met (its receptor) mRNA are
      coexpressed in the fetal liver in the middle and late stages, when hemopoiesis is
      most active. HGF and c-met mRNA are also expressed in the stromal cells of both
      fetal liver and bone marrow. Human HGF (2 to 20 ng/ml) enhances colony-forming
      units in culture (CFU-C) counts and cobblestone colony counts in the long-term
      cultures of the fetal liver and bone marrow, although HGF has no effect on
      freshly isolated bone marrow or fetal liver cells in the CFU-C assay. However,
      when the bone marrow or fetal liver cells are cocultured with HGF in the presence
      of IL-3, CFU-C counts increase. In humans, it has also been shown that HGF in the
      presence of erythropoietin induces the formation of erythroid burst-forming unit
      (BFU-E) colonies from CD34+ cells purified from the bone marrow, peripheral
      blood, or cord blood. This review discusses the role of HGF as a regulator in
      hemopoiesis.

PMID- 9031112
TI  - Comparative preclinical study of three bone marrow purging methods using PCR
      evaluation of residual t(14;18) lymphoma cells.
AB  - The t(14;18) chromosomal translocation occurring in most follicular lymphomas can
      be exploited by a Bcl2/JH polymerase chain reaction (PCR) to detect residual
      disease and to monitor the effectiveness of ex-vivo tumor cell immunological
      purging. We first demonstrated the 10(-5) Bcl2/JH PCR sensitivity with serial
      dilutions of OCY-LY8 lymphoma cell lines in normal mononuclear cells; and then
      the specificity and reproductibility of this technique by analysing follicular
      and non follicular lymphoma samples. With the Bcl2/JH PCR, we tested the
      efficiency of three marrow purging protocols with an experimentally contaminated
      bone marrow either treated by three anti-B cell monoclonal antibodies (mAb)
      followed by three rounds of rabbit complement or two rounds of immunomagnetics
      beads. Samples obtained after each purging were amplified by Bcl2/JH PCR and
      hybridized with PFL3 probe. We were able to produce a 2 to 3 log tumor cell
      reduction after three rounds of complement and a 4 to 5 log reduction after two
      rounds of beads. This study showed that it is feasible to use the Bcl2/JH PCR
      technique for residual cell lymphoma detection in patients undergoing intensive
      chemotherapy or BM transplantation. These results indicate that ex-vivo
      immunomagnetic BM purging is probably superior to complement mediated lysis for
      the eradication of B lymphoma cells from the marrow of patients undergoing
      autologous transplantation.

PMID- 9031111
TI  - Peripheral blood progenitor cell mobilization with Dexa-Beam/G-CSF, ether lipid
      purging, and autologous transplantation after high-dose CBV treatment: a safe and
      effective regimen in patients with poor risk malignant lymphomas.
AB  - High-dose chemotherapy followed by autologous peripheral blood progenitor cell
      transplantation (PBPCT) is increasingly applied in patients with relapsed, poor
      risk malignant lymphomas. Different strategies for progenitor cell mobilization
      using cytoreductive chemotherapy, hematopoietic growth factors, or both have been
      described. We studied the safety and efficacy of a modified DexaBEAM regimen
      (dexamethasone, BCNU [carmustine], etoposide, ara-C, melphalan) followed by
      granulocyte-colony stimulating factor (G-CSF) that was administered in order to
      minimize any residual disease and to obtain a sufficient amount of progenitor
      cells in the autografts. Until now, 16 patients at poor risk (8 with Hodgkin's
      disease, 8 with non-Hodgkin's lymphoma) entered the study. All the 12 patients
      with measurable disease at study entry responded to DexaBEAM. Median time of
      subsequent leukopenia (leukocytes < 1.000/microL) was 6 days (range 5-8 days).
      Peak numbers of CD34+ hematopoietic progenitor cells appeared in the peripheral
      blood after a median of 20 days (range 18-22 days) after onset of therapy. At
      that time, peripheral mononuclear cells were collected for autografting.
      Thereafter, the leukapheresis products were frozen until the day of
      transplantation, either unpurged in the case of Hodgkin's disease or purged with
      the ether lipid edelfosine in cases of non-Hodgkin's lymphoma. After high-dose
      chemotherapy with the CBV regimen (cyclophosphamide, BCNU, etoposide) the
      patients received their autografts, followed again by G-CSF treatment. A stable
      hematopoietic recovery was reached with granulocytes > 2.000/muL within 11 days
      (range 8-17 days), and platelets > 50.000/microL within 15 days (range 10-31
      days), respectively, without significant differences between the purged and
      unpurged transplants. After a median follow-up of 28 months (range 1-40 months) 7
      patients are alive without signs of recurrent disease, while 1 patient has died
      due to acute treatment related toxicity. Three patients had refractory disease,
      and 5 have relapsed of whom 4 have died. In summary, the DexaBEAM/G-CSF/CBV
      strategy appears to be safe and effective for salvage treatment in patients with
      poor risk malignant lymphomas.

PMID- 9031113
TI  - Infectious mononucleosis and Hodgkin's disease--a similar seasonality.
AB  - The presentation of Hodgkin's disease and acute infectious mononucleosis
      (glandular fever) due to Epstein-Barr virus, have similar seasonal features with
      the peak incidence around March. The extent of seasonal variation is also
      similar. Seasonality of Hodgkin's disease is most obvious and also significant in
      adult age groups below the age of 40. Amongst those over 40 years, seasonality
      was no longer present in the 40-59 but returned over age 60. Seasonal similarity
      does not prove a relationship. However two speculations are made on possible
      mechanisms. Firstly glandular fever may accelerate presentation in young adults,
      destined to present with HD. Secondly the Epstein-Barr virus may have an inherent
      seasonal behaviour whether causing acute infectious mononucleosis or when latent
      and playing a role in the aetiology of Hodgkin's disease.

PMID- 9031114
TI  - Hodgkin's disease variant of Richter's syndrome: experience at a single
      institution.
AB  - Patients developing Hodgkin's disease (HD) after a diagnosis of chronic
      lymphocytic leukemia (CLL), are frequently included in a series of patients with
      Richter's syndrome (RS). We sought to determine the natural history of the
      association of CLL and HD. Over a 21 year period, 1374 patients with CLL have
      been registered in our computer data base. Seven cases of CLL and HD have been
      documented and confirmed. The median age of these patients was 71 years (range 44
      77) and clinical features included male gender (86%), B symptomatology (86%),
      rapidly progressive lymphadenopathy (71%), prior CLL therapy (71%), advanced Ann
      Arbor stage (86%), marrow involvement with HD (43%), and autoimmune hemolytic
      anemia (29%). HD was documented by excisional lymph node biopsy in six cases and
      splenectomy in one. Mixed cellularity HD was shown in six and nodular sclerosis
      in one. Five of the biopsies revealed intervening areas consistent with small
      lymphocytic lymphoma. The Sternberg-Reed (SR) cells were CD15+ in 6/7 cases, and
      Ki-1+ in the 6 patients tested. CD45 and CD20 staining of the SR cells was
      nonreactive. The median time to development of HD was 45 months (range 0 to 96).
      The overall responses to different chemotherapy regimens was approximately 25%
      with only one CR. Six patients have died at 3, 9, 10, 13, 15 and 36 months and
      one patient is alive with progressive disease at 11 months. Our data suggests
      that CLL patients have a heightened risk for HD, features of advanced HD on
      presentation, and a poor response rate with short survival.

PMID- 9031115
TI  - A single-center study of 11 patients with intraocular lymphoma treated with
      conventional chemotherapy followed by high-dose chemotherapy and autologous bone
      marrow transplantation in 5 cases.
AB  - Intraocular lymphoma (IOL) is a rare form of non Hodgkin lymphoma (NHL); it has a
      poor prognosis and is frequently associated with central nervous system (CNS)
      infiltration. We report the results of a prospective study of 11 patients with
      IOL who received conventional chemotherapy (CT), followed by salvage high-dose
      (HD) CT with autologous bone marrow transplantation (ABMT) in five cases. All 11
      patients had abnormal funduscopic findings and six had CNS involvement at
      diagnosis. The diagnosis was based on vitrectomy in 10 cases and cerebral
      stereotaxic biopsy in one. Pathologic studies showed large-cell NHL in all cases.
      These large-cell NHL were of the B-cell type in 8 cases and of the T-cell type in
      two. First-line therapy consisted of a combination of cisplatin 25 mg/m2 as a 24
      hour IV infusion on 4 consecutive days, VP-16 40 mg/m2 for 4 days, aracytine 2
      g/m2 IV on day 5, and methylprednisolone 500 mg IV daily for 5 days (ESHAP) in 5
      cases; alternating courses of ESHAP and HD methotrexate (MTX) in 4 cases; and HD
      MTX in 2 cases. Three patients underwent ocular and whole-brain radiation
      therapy. Five refractory patients subsequently received intensive CT with
      thiotepa 750 mg/m2, busulfan 10 mg/kg and cyclophosphamide 120 mg/kg, followed by
      ABMT. First-line treatment failed in 10 evaluable cases. One patient died of CNS
      progression at 12 months. All the patients who underwent intensive CT and ABMT
      entered CR; two relapsed at 6 months and three are alive in CR 15, 15 and 14
      months after ABMT. Six patients are alive with persistent disease at 8, 13, 14,
      15, 18 and 24 months. It seems in conclusion that, high-dose thiotepa, busulfan
      and cyclophosphamide followed by ABMT is effective in some cases of refractory
      IOL.

PMID- 9031116
TI  - Effects of interferon-alpha and -gamma on B cell differentiation in
      macroglobulinemia.
AB  - We previously showed that clonal blood B cells from patients with
      macroglobulinemia spontaneously differentiate in vitro to plasma cells via an IL
      6 autocrine pathway. Here we investigate whether interferon-alpha or -gamma would
      interfere with B cell differentiation either in patients with IgM gammopathy of
      undetermined significance (IgM-MGUS) or Waldenstrom's macroglobulinemia (WM). A
      65% inhibition of in vitro B cell differentiation was noted in 8 of 10 patients
      in the presence of either interferon-alpha or -gamma. Cells from 4 patients (3
      IgM-MGUS and 1 WM) were susceptible to both types of interferon while B cell
      differentiation from 4 patients (3 IgM-MGUS and 1 WM) was inhibited only by one
      type of interferon. During in vitro culture, IL6 synthesis was unaffected by the
      presence of interferon alpha or gamma in the 8 cases studied. Likewise, no
      modulation of the constitutive B cell IL6-R expression from 6 patients studied (4
      WM and 2 IgM-MGUS) was observed. These data indicate that interferons did not
      modify the differentiation of B cells in macroglobulinemia via modulation of the
      IL6-IL6-R pathway. This is in contrast with the mode of action of interferons in
      other lymphoid malignancies such as multiple myeloma or chronic lymphocytic
      leukemia where they directly modulate IL6-production and/or IL6-R expression.

PMID- 9031117
TI  - Investigation of the RB-1 tumour suppressor gene in a United Kingdom series of
      non-Hodgkin's lymphomas.
AB  - We have investigated the RB-1 tumour suppressor genes in a series of 20 non
      Hodgkin's lymphomas (NHL). Polymerase chain reaction (PCR) amplification of
      polymorphic alleles indicated that there was evidence of allelic imbalance around
      13q14, the site of the RB-1 gene, in at least 5 NHL. Immunohistochemical analysis
      of the RB-1 protein demonstrated wide variations in the percentage of cells
      exhibiting positive staining, but these usually correlated with differences in
      the proliferation index as indicated by staining of Ki67. Only 3/35 NHL exhibited
      significantly fewer cells expressing RB-1 protein than expressed Ki167. A
      comprehensive analysis of the mutation status of RB-1 in 20 NHL was carried out
      using PCR based strategies involving single strand conformational polymorphism
      (SSCP) gels. Most of the protein coding region was studied by analysing cDNA
      derived from its mRNA and the remaining 5'-end of the coding region investigated
      by analysing exon I of the gene. We also examined the promoter region of the
      gene. In none of the 20 NHL investigated were we able to identify a mutation: the
      only abnormal migrating fragment observed proved to be a polymorphism in exon I
      of the gene in 5 NHL. In one other case we detected instability at an intron
      repeat sequence, which had occurred during progression of the disease, but again
      no mutation of the protein coding region was found. The low levels of RB-1
      protein expression that we had observed in a few of our NHL therefore did not
      appear to be due to mutation of the gene. These data suggest that mutation of RB
      1 is not a common event in the evolution of NHL, but that there may be another,
      as yet unidentified, tumour suppressor gene near the RB-1 locus which is
      associated with NHL.

PMID- 9031118
TI  - Humoral immune abnormalities in T-cell large granular lymphocyte leukemia.
AB  - The prevalence of humoral immune dysfunction has not been defined in a large
      series of patients with T-cell large granular lymphocyte leukemia (T-LGL)
      confirmed to be clonal by T-cell receptor analysis. Therefore we evaluated the
      presence of multiple autoantibodies in 27 patients with this disease. Humoral
      immune abnormalities included: rheumatoid factor (RF) (15/27 patients),
      antinuclear antibody (ANA) (13/27 patients), polyclonal hypergammaglobulinemia
      (15/24 patients), elevated serum immunoglobulins (17/26 patients), immune complex
      formation (18/25 patients), elevated beta-2 microglobulin (13/18 patients) and
      neutrophil-reactive IgG (18/20 patients). Disease manifestations in these
      patients were due to complications of cytopenia or autoimmune abnormalities.
      Infection was a common finding (21/27 patients) and likely reflected their
      neutropenia. Rheumatoid arthritis (11/27 patients), anemia (12/27 patients) and
      thrombocytopenia (10/27 patients) were less common but still frequently observed.
      This study demonstrates the presence of multiple autoantibodies in a large series
      of patients with documented clonal T-LGL proliferations.

PMID- 9031119
TI  - Detection of Epstein-Barr virus by PCR analyses in lymphoproliferative disease of
      granular lymphocytes.
AB  - We assayed peripheral blood mononuclear cells (PBMC) of fifty-eight patients with
      lymphoproliferative disease of granular lymphocytes (LDGL) for Epstein-Barr viral
      sequences. Phenotype analyses of the leukemic cell population(s) were also
      performed with a panel of monoclonal antibodies (MAb) to determine the lineage of
      the affected cells. Patients were shown to have proliferations of either CD3+ (T
      cell)LGL or CD3-(NK cell)LGL. Clonal studies showed that all CD3+ leukemic cells
      were clonally derived while none of the CD3-populations were. The CD3-leukemic
      cells were further studied through the use of two MAb, EB6 and GL183, that
      identify specific subsets of NK cells. Remarkably, 14 of 16 patients studied had
      skewed NK cell populations as compared to normal controls. Six of these patients
      had EBV detectable in their PBMC; moreover, EBV was found in all three LDGL
      patients with an EB6 + GL183-NK phenotype. Of the CD3+ patients, only six of
      thirty-nine contained EBV sequences in their PBMC. These results indicate that
      EBV is not the cause of the LDGL seen in these patients; however, there may be a
      specific subset of NK cells that respond directly to EBV infection.

PMID- 9031120
TI  - Endogenous murine leukemia virus DNA sequences in murine cell lines: implications
      for gene therapy safety testing by PCR.
AB  - Safety testing for replication-competent retrovirus (RCR) is an important
      requirement in gene transfer clinical trials using retroviral vectors. A
      sensitive polymerase chain reaction (PCR) method is one approach to RCR
      detection. Only in the presence of RCR will the pol-env encoding sequences,
      necessary for viral replication and packaging, be amplified from proviral DNA in
      infected indicator cells. To avoid false-positive results in this assay it is
      crucial that indicator cell lines are free of endogenous retroviral sequences
      that could also be amplified with pol-env PCR primers. We screened candidate
      murine indicator cell lines and determined that while Mus dunni is free of
      detectable pol-env sequences, endogenous retroviral sequences do indeed exist in
      several cell lines and lead to false-positive results in the PCR assay for RCR.
      Furthermore, these endogenous retroviral sequences are expressed as RNA
      transcripts in NIH 3T3 and SC-1 cell lines, as determined by PCR amplification of
      cDNA but, nevertheless, do not give rise to replication-competent particles. We
      recognize the potential for murine cell lines to undergo spontaneous
      rearrangements of endogenous viral sequences in culture and give rise to
      recombinants containing newly acquired contiguous pol-env sequences. Indicator
      cell lines should thus be carefully selected and monitored on an ongoing basis
      when used in safety testing using PCR approaches for the detection of RCR.

PMID- 9031121
TI  - C-Myc and Bcl-2 protein expression during the induction of apoptosis and
      differentiation in TNF alpha-treated HL-60 cells.
AB  - We examined c-Myc and Bcl-2 protein expressions during the induction of apoptosis
      and differentiation in TNF alpha-treated HL-60 cells using a two-color flow
      cytometric method. We found that c-Myc protein was rapidly down-regulated in the
      apoptotic cells while Bcl-2 protein was expressed at relatively high levels.
      Concomitantly with terminal differentiation Bcl-2 protein was down-regulated in
      differentiating cells as well as c-Myc protein. We also showed that c-myc
      antisense oligonucleotides could induce apoptosis in HL-60 cells whereas bcl-2
      antisense did not induce apoptosis during the early time of treatment. These
      results suggest that the down-regulation of c-Myc protein expression is a primary
      event to induce apoptosis and neither consistent expression of c-Myc protein nor
      rapid down-regulation of Bcl-2 protein is necessary for the initial processing of
      apoptosis in HL-60 cells. Furthermore, concomitant down-regulation of c-Myc and
      Bcl-2 is closely associated with terminal differentiation and apoptotic cell
      death of HL-60 cells treated with TNF alpha.

PMID- 9031122
TI  - Primary lymphoma of the skull presenting as multiple cranial nerve palsies.
AB  - Lymphoma presenting with isolated diffuse infiltration of the skull is
      exceedingly rare, with less than 20 previously reported cases. The clinical
      presentation of a 73-year-old female with primary lymphoma of the skull,
      manifesting multiple cranial nerve palsies and infiltration of the temporalis
      muscles is described. MRI of the head, revealed an abnormal signal from the
      diploic space of the call varium and skull base on both T1 and T2 weighted
      images, infiltration of the temporalis muscles and clivus, and diffuse meningeal
      enhancement encroaching on the cavernous sinus bilaterally. Biopsy of temporalis
      muscle and skull showed a diffuse large cell lymphoma, B-cell type. Staging
      workup failed to reveal any other sites of disease. Despite multiple cranial
      nerve palsies, there was no evidence of leptomeningeal disease on CSF
      examination. MRI was instrumental in demonstrating the abnormalities that lead to
      the diagnostic biopsy.

PMID- 9031123
TI  - Granulocytic sarcoma of the chest wall at site of Hickman catheter tract.
AB  - Insertion of a Hickman central venous catheter before administration of induction
      chemotherapy is a common practice in treatment of patients with acute
      myeloblastic leukemia (AML). Granulocytic sarcoma associated with AML may be the
      initial clinical manifestation of newly diagnosed or relapsed AML, heralding
      systemic involvement by weeks to months. A case of granulocytic sarcoma of the
      chest wall occurring as subcutaneous nodules along a scar of a previous Hickman
      catheter tract in a 45 year old female patient with AML is described. The patient
      who was in first complete remission, developed granulocytic sarcoma
      simultaneously with complaints associated with leukemic CNS infiltration. This is
      the second case described of granulocytic sarcoma of the chest wall at the site
      of a Hickman catheter tract. The simultaneous CNS and chest wall manifestations
      raise the interesting question whether both sites behaved as sanctuaries for
      resistant leukemic cells, in this case.

PMID- 9031124
TI  - Resolution of autoimmune hemolytic anemia following splenectomy in CD3+ large
      granular lymphocyte leukemia.
AB  - A 24 year old female with a 4 year history of anemia and absolute lymphocytosis
      was evaluated and found to have T cell large granular lymphocyte (T-LGL) leukemia
      associated with autoimmune hemolytic anemia, neutropenia, mild thrombocytopenia
      and splenomegaly. In an effort to ameliorate her symptomatic cytopenias, she was
      treated with prednisone and subsequently methotrexate without success. In
      February 1993, she underwent splenectomy for symptomatic anemia. Splenectomy
      resulted in an increased hemoglobin concentration to normal levels, resolution of
      all laboratory evidence of hemolysis, and disappearance of thrombocytopenia. This
      response has been durable despite persistence of the abnormal LGL clone. We
      suggest that splenectomy may be an effective treatment for autoimmune hemolytic
      anemia and/or thrombocytopenia often associated with T-LGL leukemia. As this
      disease often exhibits a chronic clinical course with morbidity resulting from
      consequences of resultant cytopenias rather than visceral involvement with
      leukemic LGL, effective treatment of cytopenias despite persistence of the
      abnormal LGL clone is beneficial.

PMID- 9031125
TI  - PCR. Basic principles and routine practice.

PMID- 9031127
TI  - Amplification of DNA sequences up to 5 kb from small amounts of genomic DNA using
      tub DNA polymerase.

PMID- 9031126
TI  - XL PCR amplification of long targets from genomic DNA.

PMID- 9031128
TI  - One-step optimization using touchdown and stepdown PCR.

PMID- 9031129
TI  - GC-rich template amplification by inverse PCR. DNA polymerase and solvent
      effects.

PMID- 9031131
TI  - Using T4 DNA polymerase to generate clonable PCR products.

PMID- 9031130
TI  - Coupled one-step reverse transcription and polymerase chain reaction procedure
      for cloning large cDNA fragments.

PMID- 9031132
TI  - Rapid (ligase-free) subcloning of PCR products.

PMID- 9031134
TI  - Cloning unmodified PCR products using engineered XcmI restriction sites in a
      portable cassette.

PMID- 9031133
TI  - Cloning PCR products utilizing the T/A overhang and a kit.

PMID- 9031135
TI  - A T-linker strategy for modification and directional cloning of PCR products.

PMID- 9031136
TI  - Recovery of DNA amplification products from silver-stained polyacrylamide gels.
      Applications in nucleic acid fingerprinting and genetic mapping.

PMID- 9031137
TI  - Recombination and site-directed mutagenesis using recombination PCR.

PMID- 9031138
TI  - In vitro recombination and mutagenesis of DNA. SOEing together tailor-made genes.

PMID- 9031139
TI  - In-frame cloning of synthetic genes using PCR inserts.

PMID- 9031140
TI  - Creation of chimeric junctions, deletions, and insertions by PCR.

PMID- 9031141
TI  - Mutagenesis and gene fusion by megaprimer PCR.

PMID- 9031143
TI  - Thermostable ligase-mediated incorporation of mutagenic oligonucleotides during
      PCR amplification.

PMID- 9031142
TI  - Rapid and efficient one-tube PCR-based mutagenesis method.

PMID- 9031144
TI  - Linker scanning mutagenesis by three-step PCR.

PMID- 9031145
TI  - Sequence inversion by Flip-PCR.

PMID- 9031146
TI  - PCR site-directed mutagenesis using Pyrococcus sp GB-D polymerase coupled to a
      rapid screening procedure. Application to a beta-glucanase gene.

PMID- 9031147
TI  - Using the SELEX combinatorial chemistry process to find high affinity nucleic
      acid ligands to target molecules.

PMID- 9031148
TI  - Rapid amplification of cDNA ends.

PMID- 9031149
TI  - Amplification of gene-regulating regions with single-sided specificity.

PMID- 9031150
TI  - An end-trimming method and its application to amplify adjacent cDNA and genomic
      DNA fragments by PCR.

PMID- 9031151
TI  - Anchoring a defined sequence to the 5' ends of mRNAs. The bolt to clone rare full
      length mRNAs.

PMID- 9031152
TI  - Rapid directional walk within DNA clones by step-out PCR.

PMID- 9031153
TI  - Inverse PCR. An efficient approach to cloning cDNA ends.

PMID- 9031154
TI  - Rapid amplification of gene ends (RAGE) from gene libraries by anchored PCR.

PMID- 9031155
TI  - Isolation of coding sequences from yeast artificial chromosome (Yac). Clones by
      exon amplification.

PMID- 9031156
TI  - cDNA libraries from a low amount of cells.

PMID- 9031157
TI  - Rapid and nonradioactive screening of recombinant libraries by PCR.

PMID- 9031158
TI  - Use of PCR for cDNA library screening.

PMID- 9031159
TI  - Generation and PCR screening of bacteriophage gamma sublibraries enriched for
      rare clones (the "sublibrary method").

PMID- 9031160
TI  - Normalization of cDNA sequence representation by molecular selection.

PMID- 9031161
TI  - Subtractive cDNA cloning using magnetic beads and PCR.

PMID- 9031162
TI  - Generation of a PCR-renewable source of subtractive cDNA.

PMID- 9031163
TI  - The use of PCR for differential screening of cDNA libraries.

PMID- 9031164
TI  - Identification and cloning of differentially expressed genes by DDRT-PCR.

PMID- 9031165
TI  - Cloning gene family members using PCR with degenerate oligonucleotide primers.

PMID- 9031166
TI  - Amplification using degenerate primers with multiple inosines to isolate genes
      with minimal sequence similarity.

PMID- 9031167
TI  - Designing PCR primers to amplify specific members or subgroups of multigene
      families.

PMID- 9031168
TI  - Screening gene family-enriched cDNA sublibraries with an unamplified cDNA probe.
      Focusing on moderately to abundantly expressed clones.

PMID- 9031192
TI  - Preparation of neuropeptide-containing fractions from biological materials.

PMID- 9031193
TI  - Purification of extracted peptides for structural analysis.

PMID- 9031194
TI  - Amino acid sequencing of neuropeptides.

PMID- 9031195
TI  - Neuropeptide gene identification using the polymerase chain reaction.

PMID- 9031196
TI  - Solid-phase synthesis of neuropeptides by Fmoc strategies.

PMID- 9031197
TI  - Incorporation of stable pseudopeptide bonds. Methylene amino, thioether, and
      hydroxyethylene derivatives.

PMID- 9031199
TI  - Purification of synthetic peptides by high performance liquid chromatography.

PMID- 9031198
TI  - Synthesis of conformationally restricted peptides.

PMID- 9031200
TI  - Molecular weight estimation for neuropeptides using size-exclusion high
      performance liquid chromatography.

PMID- 9031201
TI  - Molecular weight determinations using polyacrylamide gel electrophoresis with
      tris-tricine buffers.

PMID- 9031202
TI  - Determination of neuropeptides by capillary electrophoresis.

PMID- 9031203
TI  - Characterization of neuropeptide processing by fast atom bombardment mass
      spectrometry.

PMID- 9031204
TI  - Analysis of neuropeptides by size-exclusion HPLC linked to electrospray
      ionization mass spectrometry.

PMID- 9031206
TI  - Use of circular dichroism to determine secondary structure of neuropeptides.

PMID- 9031205
TI  - Identification of peptides by matrix-assisted laser desorption ionization time of
      flight mass spectrometry (MALDI-TOF-MS) and direct analysis of the laterobuccal
      nerve from the pond snail Lymnaea stagnalis.

PMID- 9031207
TI  - 1H nuclear magnetic resonance (NMR) in the elucidation of peptide structure.

PMID- 9031208
TI  - The study of membrane- or receptor-bound neuropeptides by NMR.

PMID- 9031209
TI  - Molecular modeling of neuropeptides.

PMID- 9031210
TI  - Tritium labeling of neuropeptides.

PMID- 9031211
TI  - The use of IODO-GEN for preparing 125I-labeled peptides and their purification by
      reversed-phase high performance liquid chromatography.

PMID- 9031212
TI  - Production of antisera using peptide conjugates.

PMID- 9031213
TI  - Radioimmunoassay.

PMID- 9031214
TI  - Enzyme-linked immunosorbent assay of peptides.

PMID- 9031215
TI  - Sample preparation for peptide immunocytochemistry.

PMID- 9031216
TI  - Immunocytochemical methods for regulatory peptides.

PMID- 9031218
TI  - Preparation of a membrane fraction for receptor studies and solubilization of
      receptor proteins with retention of biological activity.

PMID- 9031219
TI  - Radioligand binding using 125I-labeled peptides.

PMID- 9031217
TI  - Ultrastructural localization of peptides using immunogold labeling.

PMID- 9031220
TI  - Analysis of data from "cold saturation" radioligand binding experiments.

PMID- 9031222
TI  - Measurement of efflux rates from brain to blood.

PMID- 9031221
TI  - Organ/tissue preparations for the assessment of agonist/antagonist activity.

PMID- 9031223
TI  - Assay of neuropeptidases using fluorogenic substrates.

PMID- 9031224
TI  - Characterization of neuropeptidases using inhibitors.

PMID- 9031257
TI  - Glial, vascular, and neuronal cytogenesis in whole-mounted cat retina.
AB  - A method was developed for detecting cytogenesis in retinal whole-mount
      preparations by bromodeoxyuridine (BrdU) immunohistochemistry. Because BrdU is a
      nonspecific marker that labels all cells in the S phase of the cell cycle, it is
      ideally combined with other cell-specific markers to study the cytogenesis of
      specific cell types. Double-label protocols to visualize mitotically active
      astrocytes and cells associated with the forming vasculature have been developed
      and applied to the retina. This approach revealed that, during normal development
      of the kitten retina, vascular mitogenesis occurs predominantly in the ganglion
      cell and nerve fiber layers, where the inner retinal plexus is formed by a
      process involving transformation of mesenchymal precursor cells and division of
      vascular endothelial cells. The peak density of vascular mitogenesis moved in a
      central-to-peripheral manner and was associated with the leading edge of the
      forming capillary plexus. A small number of dividing vascular endothelial cells
      was also associated with angiogenesis, the process responsible for the formation
      of the outer retinal plexus, vessels at the area centralis, and the radial
      peripapillary capillaries. Cytogenesis associated with astrocytes occurred in the
      ganglion cell and nerve fiber layers but was apparent predominantly at or close
      to the optic nerve head. Confirming earlier studies, neuronal mitogenesis was
      shown to occur predominantly at the ventricular zone, first at the area centralis
      and spreading peripherally with increasing maturity. A second region of neuronal
      cytogenesis, at the subventricular zone, was also apparent. Tissue hyperoxia
      decreased the rate of vasculogenic cell division but had no apparent effect on
      neurogenic or astrocytic cell division. Four distinct zones of cell generation
      were therefore identified within the retina, each associated with either glial,
      vascular, or neuronal cytogenesis. Thus, BrdU immunohistochemistry in whole
      mounted retinal preparations offers a fast and reliable alternative to
      [3H]thymidine autoradiography for the study of the topography of cytogenesis
      during development.

PMID- 9031258
TI  - Distribution of S100 immunoreactivity in the retina and optic nerve head of the
      teleost Tinca tinca L.
AB  - The distribution of S100 immunoreactivity within the normal and regenerating
      retina and optic nerve head of the teleost Tinca tinca L. has been investigated
      using the avidin-biotin complex (ABC) method and a polyclonal antibody against
      S100. Astrocytes and Muller cells were labeled with this antibody. This
      represents the first description of astrocytes localized in the optic nerve head
      and in the nerve fiber layer of the fish retina displaying a typical bipolar
      morphology. Horizontal cells in the inner nuclear layer were immunolabeled; we
      also observed species-specific S100 labeling of horizontal cells of the H1
      subtype. No significant changes were seen in the S100 immunoreactive Muller
      cells, astrocytes, or horizontal cells in the tench retina after optic nerve
      crushing and during regeneration. These results might help to understand the
      function of glial cells in the normal and experimentally induced regenerating
      fish visual system.

PMID- 9031259
TI  - Dopaminergic and GABAergic retinal cell populations in mammals.
AB  - A number of modern techniques now allow histologists to characterize
      subpopulations of retinal neurons by their neurotransmitters. The morphologies
      and connections of these chemically defined neurons can be analyzed precisely at
      both light and electron microscope levels and lead to a better understanding of
      retinal circuitry. The dopaminergic neurons form a loose population of special
      wide-field amacrine cells bearing intraretinal axons within the inner plexiform
      layer. One subtype, the interplexiform cell, sends an axon to the outer plexiform
      and outer nuclear layers. The number of interplexiform cells is variable
      throughout mammalian species. The GABAergic neurons form a dense and
      heterogeneous population of amacrine cells branching at all levels of the inner
      plexiform layer. The presence of GABA in horizontal cells seems to be species
      dependent. Close relationships occur between dopaminergic and GABAergic cells.
      GABA antagonizes a number of dopaminergic actions by inhibiting both the release
      and synthesis of dopamine. This inhibition can be supported by GABA synapses onto
      dopaminergic cells, but GABA can also diffuse to its targets. Finally, GABA is
      also contained and synthesized in dopaminergic cells. This colocalization might
      be the basis of an intracellular modulation of dopamine by GABA.

PMID- 9031260
TI  - Light adaptation affects synaptic vesicle density but not the distribution of
      GABAA receptors in goldfish photoreceptor terminals.
AB  - GABA is a likely feedback transmitter from H1 horizontal cells to cone
      photoreceptors in fish retinas. Spinules arise from H1 cell dendrites in light
      adapted retinas, are correlated with responses attributed to feedback, and have
      been proposed to be the GABA release sites. We used mAb 62-3G1, an antibody
      against the beta 2/beta 3 subunits of the GABAA receptor complex, to visualize
      GABAA receptor immunoreactivity (GABAr-IR) in photoreceptors as a function of
      light and dark adaptation at the electron microscopical level. Regardless of
      adaptation, GABAr-IR was restricted to the synaptic terminals of all cones and
      most rods; synaptic vesicular membrane and plasma membrane, exhibited GABAr-IR.
      Contrary to expectations, the density of GABAr-IR was least on the plasma
      membrane within the invagination, regardless of the presence or absence of
      spinules. Dense GABAr-IR was observed on the lateral surface of cone pedicles, on
      cone processes proximal to the invagination, and on presumed telodendria from
      nearby cones. There was no difference in GABAr-IR of rod plasma membranes within
      or outside of the invagination or with adaptation. The only novel effect of
      adaptation was in regards to the density of synaptic vesicles. Cones showed a 29%
      increase in vesicle density with dark adaptation, whereas rods showed a 17%
      decrease. We conclude that all goldfish photoreceptors will be GABA-sensitive and
      that the sensitivity is distributed over the surface of the synaptic terminal
      rather than localized to within the invagination. The role of spinules in GABA
      release remains to be determined, but we conclude that spinules are not related
      to the GABA sensitivity of goldfish photoreceptors.

PMID- 9031262
TI  - Profiling dialysis: a new approach to dialysis intolerance.

PMID- 9031261
TI  - Immunostaining with antibodies against protein kinase C isoforms in the fovea of
      the monkey retina.
AB  - We reported previously that an antibody to the alpha isoform of protein kinase C
      (PKC) immunostained rod bipolar cells and bipolar cells that could be blue-cone
      (B-cone)-specific in postmortem human retina (Kolb et al. (1993) Vis. Neurosci.
      10:341-351). In addition, we showed that antibodies to the beta isoform of PKC
      immunostained cone system bipolar, amacrine, and ganglion cells. Since the
      fixation of the human material was poor, we were unable to make positive
      identifications of the specific cell types that were immunoreactive, particularly
      in the case of PKC-beta antibodies. Thus, herein we have repeated the study on
      well-fixed monkey foveal retina. PKC-alpha immunoreactivity (IR) was restricted
      to a single type of cone bipolar cell that contacted only a minority of the cone
      pedicles at central invaginating contacts of ribbon triads. This bipolar type
      shares some morphological characteristics of B-cone-specific bipolar cells of
      primate retina. PKC-beta immunoreactivity was found in cone bipolar cells that
      made primarily basal contacts with cone pedicles and had axon terminals in
      sublamina alpha of the inner plexiform layer (IPL). Immunoreactivity also
      occurred in a type of cone bipolar that made central element contacts and had
      axon terminals in sublamina b of the IPL. Some ganglion cells, particularly those
      postsynaptic to flat midget bipolar cells also exhibited PKC-beta-IR. One type of
      amacrine with an 8 microns diameter cell body showed strong PKC-beta-IR. It was
      postsynaptic to cone bipolar cells in both sublamina a and b and presynaptic to
      bipolar axons, other immunoreactive amacrine cells, and ganglion cell dendrites
      and bodies. The other amacrine cell type showed less strong PKC-beta-IR, large
      bodied (12-15 microns cell body diameter), and probably diffuse in branching
      pattern. The latter interacted with the intensely immunoreactive amacrines,
      bipolars, and ganglion cells. By comparison to cat and primate retinas where
      morphology and physiology of many retinal neurons are well documented, we suggest
      that PKC-beta may be specific to flat midget, flat diffuse, and invaginating
      diffuse cone bipolar cells and to at least two amacrine cells. Some of these
      neural types are proposed to be involved in OFF-center cone pathways in the
      monkey retina.

PMID- 9031263
TI  - Production of hepatocyte growth factor is increased in chronic renal failure.
AB  - Hepatocyte growth factor (HGF) facilitates recovery from tissue injuries. We
      previously reported that serum HGF levels were elevated in chronic renal failure
      (CRF) patients. In the present study Western blot analysis of CRF patients' sera
      showed the majority of their serum HGF was a single-chain precursor molecule. In
      CRF rats developed by 5/6 nephrectomy or high adenine diet, both HGF mRNA
      expression levels and tissue HGF concentrations were increased in liver and
      spleen. The results suggest that HGF production increases in CRF, which may be a
      response to chronic progressive renal injuries in an endocrine manner.

PMID- 9031264
TI  - Body composition and physical performance in children after renal
      transplantation.
AB  - Body composition using standard anthropometric methods and dual-energy X-ray
      absorptiometry (DEXA) was determined in a cross-sectional study among 26
      pediatric renal transplant recipients. At the same time, spiroergometry exam,
      pulmonary function tests, dynamometry and tremometry exams were performed in all
      patients. Fat body mass obtained by DEXA correlated inversely with maximal
      physical load during spiroergometry exam (r2 = 0.51, p = 0.0001). The study
      demonstrates good tolerance of increased physical load in children after renal
      transplantation. An inverse relationship was found between fat body mass and
      physical performance. Exercise training programs for children after renal
      transplantation are therefore suggested.

PMID- 9031265
TI  - Role of preoperative donor-specific transfusion and cyclosporine in haplo
      identical living related renal transplant recipients.
AB  - A prospective randomized trial of use of donor-specific transfusion and
      cyclosporine given 24 h before operation was performed in living related renal
      transplant recipients. The benefits, disadvantages and effect on graft and
      patient outcome was analyzed. Cyclosporine was started 72 h before operation and
      48 h before donor-specific transfusion (DST). Fifteen patients received DST while
      another 15 age- and sex-matched living related renal allograft recipients on
      similar immunosuppression served as controls. Patient and donor demographics were
      similar in the two groups. The DST group had significantly fewer rejection
      episodes than the control group (0.26 vs. 1.1 rejection episode per patient, p <
      0.01). There were fewer episodes of acute rejection in the first 3 months
      posttransplant in the DST group. Hyperresponder recipients (as tested by mixed
      lymphocyte cultures) also benefitted by DST which significantly reduced the
      number of acute rejection episodes (0.25 vs. 1 episode per hyperresponder
      patient, DST vs. control, p < 0.05). The need for dialysis, incidence of
      infections and other complications were similar in the two groups. Graft function
      at 3, 6, 9 and 12 months after transplant was significantly better in the DST
      group (p < 0.05). Graft survival at 1 year in DST group (85.5%) was not
      statistically different than control (74.8%). In conclusion, DST and cyclosporine
      given 24 h before live related renal transplantation is effective in improving
      graft function and reducing the number of acute rejection episodes which could
      have a beneficial effect on long-term graft survival.

PMID- 9031266
TI  - Helicobacter pylori in kidney allograft recipients: high prevalence of
      colonization and low incidence of active inflammatory lesions.
AB  - Since kidney transplant recipients are at enhanced risk for developing severe
      upper gastrointestinal disease and Helicobacter pylori (Hp) is an important
      pathogen in active gastritis and peptic ulcer, we performed gastroduodenoscopic
      examination, coupled with assessment of Hp colonization in 29 renal allograft
      recipients complaining of recurrent dyspepsia. Results were compared with those
      of 25 chronically hemodialyzed patients and 16 subjects free from renal disease,
      also suffering from upper gastrointestinal symptoms of similar severity. We found
      that while transplant recipients have had a high prevalence of Hp infection (62
      vs. 34.6% in dialysis and 43.6% in control dyspeptic patients), active gastritis
      was clearly less frequently seen in these patients than in control subjects
      (transplant group: 6.9%, dialysis 3.8%, control 31.3%) and peptic ulceration was
      totally absent. Prevalence of Hp colonization was even higher in renal graft
      recipients on triple posttransplant immunosuppression (82%). In dyspeptic
      transplant and dialysis patients, colonization with Hp did not account for
      development of active inflammatory lesions, an association frequently seen in
      subjects free from renal disease and immunosuppressive therapy.

PMID- 9031267
TI  - High-performance hemodiafiltration and blood pressure stability.
AB  - In the present study, we have estimated plasma nonrefilling rate and assessed its
      relationship to blood pressure stability during hemodialysis (HD) with normal or
      high sodium dialysate and during high flux hemodiafiltration (HDF). In standard
      HD, the greater plasma nonrefilling rate resulted in the larger decrease in blood
      pressure (alpha = -6.7 +/- 0.2 mm Hg/%, p < 0.01, n = 75). When compared to
      standard HD, high flux HDF (n = 6) altered neither plasma refilling nor blood
      pressure stability. Finally, the restrictive usage of high sodium dialysate
      reduced plasma nonrefilling rate (21 +/- 3 vs. 16 +/- 2%, p < 0.05, n = 10) and
      the magnitude of decrease in blood pressure (16 +/- 6 vs. 9 +/- 4 mm Hg, p <
      0.05) without increase in interdialytic weight gain. Our data indicate relative
      safety of high performance HDF, and warrant judicious use of high sodium
      dialysate for the HD patients with hypotensive episodes.

PMID- 9031268
TI  - Exercise training and the progression of chronic renal failure.
AB  - The possible beneficial effect of regular exercise training on the progression of
      chronic renal failure was studied in a prospective randomized controlled study.
      Thirty patients with a median glomerular filtration rate (GFR) of 25 ml/(min.1.73
      m2) (range 10-43) were randomized to physical training (30 min of bicycling daily
      or an equal amount of other physical activities) or to maintenance of the usual
      lifestyle. The median maximal work capacity increased significantly in the
      exercise group and remained unchanged in the control group during a median
      observation time of 20 months whereas the rate of progression judged by the slope
      of GFR versus time plot was equal in the two groups. Hence, the beneficial effect
      of exercise training, earlier observed in rat studies, could not be reproduced in
      our patients. Physical exercise had no untoward effect on progression of renal
      disease.

PMID- 9031270
TI  - Is aluminum toxicity responsible for uremic pruritus in chronic hemodialysis
      patients?
AB  - Pruritus is a common symptom among patients undergoing long-term hemodialysis.
      However, its etiology remains unclear. In an attempt to clarify its cause we
      tried to correlate pruritus and its intensity with several serological variables
      in 94 hemodialysis patients. Our results show that higher serum aluminum
      concentrations are found in dialysis patients with pruritus (p = 0.008) and that
      the intensity of pruritus is also significantly related to the aluminum
      concentration (p = 0.007). The intensity of pruritus was also correlated with the
      calcium-phosphate product (p = 0.03). Our findings suggest that prolonged
      exposure to aluminum in patients with chronic renal failure might be involved in
      the pathogenesis of uremic pruritus and elevated calcium-phosphate product seems
      to be an additional factor predisposing to pruritus.

PMID- 9031269
TI  - Polymorphonuclear cells in chronic hemodialysis patients have intact phagocytotic
      and impaired bactericidal activities.
AB  - Although it has been well documented that chronic hemodialysis (HD) patients are
      highly susceptible to infectious diseases, the reasons for this have yet to be
      clarified. The present study was thus designed in order to better define this
      issue. Fifty-eight stable chronic HD patients without any evidence of infection
      were selected for the study. Blood samples were collected before and after HD
      from the same patient to determine the effect of HD. Reactive oxygen species
      (ROS) production in polymorphonuclear cells (PMNC) was measured by
      chemiluminescence using luminol. When the PMNC collected after HD were stimulated
      in vitro with a calcium ionophore (A23187), they produced a larger amount of ROS
      than that obtained from healthy volunteers [mean 7.4 x 10(5) photon counts (n =
      58) vs. 3.0 x 10(5) photon counts (n = 17); p < 0.01]. A higher production of ROS
      after HD was seen in patients using membranes such as cellulose triacetate,
      polymethylmetacrylate and cellulose diacetate, whereas cuprophane did not seem to
      augment ROS production at all. On the other hand, when the PMNC after HD were
      stimulated with phorbol myristate acetate, their photon counts (mean 4.3 x 10(7))
      were comparable to those before HD (mean 3.5 x 10(7)), and to those of PBMC
      obtained from healthy volunteers (mean 4.1 x 10(7)). It was thus suggested that
      the enhanced ROS production of PMNC was related to some stimuli, possibly even to
      the assay used to measure ROS. The phagocytotic activity and bactericidal effect
      of PBMC were measured by coculturing 1 x 10(5) PMNC with 1 x 10(5) CFU of
      Escherichia coli. Similar phagocytotic activities were noted in the PMNC from
      healthy volunteers and chronic HD patients before and after HD: the mean number
      of phagocytosed bacteria (log10 CFU) was 3.3, 3.3, and 3.3, respectively.
      However, in the case of a bactericidal effect, only the PMNC from healthy
      volunteers, but not the PMNC from HD patients, could effectively kill the
      bacteria, since the number of bacteria in PMNC decreased from 10(3.3) to 10(2.1).
      The PMNC from HD patients could not kill the bacteria-regardless of the
      characteristics of the membranes. It was thus concluded that the PMNC of chronic
      HD patients possess an intact phagocytotic activity which impaired bacterial
      killing, and was probably due to an abnormality occurring in the ROS production
      pathway.

PMID- 9031271
TI  - Precise ultrastructural localization of endothelial leukocyte adhesion molecule
      1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in
      patients with IgA nephropathy.
AB  - Using light and electron microscopy, we performed an immunohistochemical study of
      endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion
      molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in 15
      patients with IgA nephropathy to clarify the localization of these adhesion
      molecules. The normal portions of 2 kidneys removed due to localized carcinoma
      and 3 biopsies from patients without glomerular disease were used as a control.
      By light microscopy, ELAM-1, VCAM-1, and ICAM-1 all showed positive staining in
      IgA nephropathy, with the intensity of staining following the sequence ICAM-1 >
      VCAM-1 > ELAM-1. ELAM-1 and VCAM-1 showed a patchy distribution of moderate
      staining in the tissues, including the mesangium, crescents, adhesions, and
      tubules. In contrast, there was marked linear ICAM-1 staining throughout the
      vascular walls. ELAM-1 and VCAM-1 were positive on the basolateral surfaces of a
      few proximal tubular epithelial cells in association with inflammatory cell
      infiltration, while ICAM-1 was found on the brush border. ICAM-1 was positive in
      the glomerular capillary walls and interstitial vessels of the control kidney
      tissue, while ELAM-1 and VCAM-1 were virtually absent. By electron microscopy,
      ELAM-1 positivity on the urinary surface of the parietal/visceral epithelial
      cells was often associated with adherent mononuclear cells in the urinary space.
      VCAM-1 positivity was increased in the perinuclear space and/or cytoplasm of
      mesangial cells as well as at the mesangial cell-endothelial cell interface.
      These findings suggest that ELAM-1 and VCAM-1 may be more closely related than
      ICAM-1 to the major histopathological changes occurring in IgA nephropathy,
      including mesangial expansion, formation of crescents and adhesions, and
      tubulointerstitial injury.

PMID- 9031272
TI  - A monoclonal antibody (1F3) to human glomerular epithelial cells: a new marker
      for renal epithelial cell injury.
AB  - In order to identify a new cell surface antigen as a potential marker of renal
      epithelial cell injury, we produced a monoclonal antibody (Mab), 1F3, by
      immunizing mice with cultured human glomerular cells. Immunofluorescence (IF) and
      immunoelectron microscopy (IEM) studies demonstrated that 1F3-recognizing antigen
      (1F3 antigen) was strongly expressed on the cell surface of glomerular podocytes
      and very weakly on parietal epithelial cells. 1F3 antigen was not expressed in
      any other cells in the normal kidney. Immunoprecipitation analysis using
      metabolically labeled glomeruli revealed that 1F3 recognized a 125-kD protein
      under reducing conditions. IF studies of biopsy specimens from patients with a
      variety of glomerular and tubulointerstitial diseases showed that 1F3 antigen was
      almost negative in cellular crescents but was strongly expressed in fibrocellular
      crescents. When glomerular sclerosis appeared, the expression of 1F3 antigen
      decreased in sclerotic areas of glomeruli. 1F3 antigen became positive in
      atrophic tubules that were seen in diseased kidneys. Severity of tubular atrophy
      correlated well with the extent of tubular expression of 1F3 antigen. These
      results indicate that Mab, 1F3 marks phenotypic changes of renal epithelial cells
      under disease conditions and may be a useful marker for progressive kidney
      diseases.

PMID- 9031273
TI  - Uninephrectomy prevents the ischemia-induced increase in renin activity.
AB  - Contralateral uninephrectomy attenuates unilateral ischemic injury. The present
      work was performed to elucidate whether the beneficial effect of uninephrectomy
      was associated with the modification of ischemia-induced changes in plasma or
      renal renin activity. A 60-min left renal artery occlusion was conducted in right
      nephrectomized (Nx) and sham-nephrectomized (Sham-Nx) rats. The decline in inulin
      clearance 48 h after ischemia was significantly less in Nx rats than in Sham-Nx
      animals (0.50 +/- 0.10 vs. 0.052 +/- 0.029 ml/min/kidney, p < 0.05). Following
      ischemia, plasma renin activity (PRA) significantly increased in Sham-Nx (from
      5.4 +/- 0.9 to 15.5 +/- 1.4 ng AI/ml/min, p < 0.01) but not in Nx (from 3.5 +/-
      0.5 to 5.0 +/- 1.0 ng AI/ml/ min) animals. PRA and renal cortical renin content
      (2,200 +/- 225 vs. 1,257 +/- 187 ng AI/h/mg protein, p < 0.05) were significantly
      less in Nx rats than in Sham-Nx animals 48 h after renal ischemia. The decrease
      in body weight was greater in Nx rats than in Sham-Nx animals. Plasma atrial
      natriuretic peptide (ANP) (195 +/- 30 vs. 302 +/- 40 pg/ml, p < 0.05) and renal
      dopamine (DA) content (3.2 +/- 0.5 vs. 13.7 +/- 1.3 ng/g tissue, p < 0.01) were
      rather lower in the Nx group when compared with the Sham-Nx group. No significant
      difference was found in the intrarenal content of norepinephrine (NE) between two
      ischemic groups. These findings suggested that uninephrectomy prevents the
      ischemia-induced increase in renin activity. The prevention of the increase in
      renin activity in Nx rats is not be mediated through the modulation of ischemia
      induced changes in sodium balance, plasma ANP level and/or intrarenal contents of
      NE and DA.

PMID- 9031274
TI  - Vitamin E pretreatment prevents cyclosporin A-induced crystal deposition in
      hyperoxaluric rats.
AB  - The in vivo effect of cyclosporin A (CsA) on renal calcium oxalate (CaOx) crystal
      retention in experimental hyperoxaluric rats was investigated. Further, the
      effect of pretreatment of vitamin E on the above conditions was also studied.
      Male Wistar rats were divided into two major groups each containing 40 rats. One
      of the groups was pretreated with vitamin E. Both major groups were then
      subgrouped into four groups: group 1 received the vehicle (olive oil); group 2
      received CsA in olive oil (50 mg/kg); group 3 received 3% ammonium oxalate
      (AmOx), and group 4 received CsA + AmOx. Nephrotoxicity was assessed by the
      activities of urinary marker enzymes and also by histopathology. Urinary oxalate
      excretion as well as the activities of lactate dehydrogenase, gamma
      glutamyltranspeptidase, alkaline phosphatase and inorganic pyrophosphatase
      enzymes were elevated either in CsA-alone or AmOx-alone treated groups. On
      combined administration of both CsA and AmOx, further elevations of these enzymes
      were observed. Urinary excretion of oxalate concentration positively correlated
      with urinary excretion of these enzymes. Deposition of CaOx crystals was seen
      only in the kidneys of rats that received combined treatment. On pretreatment
      with vitamin E the observed increased urinary activities of the enzymes and
      oxalate, histopathological changes and the deposition of CaOx crystals by
      administration of CsA in hyperoxaluria were prevented suggesting that vitamin E
      could be supplemented to prevent CsA-induced membrane damage.

PMID- 9031275
TI  - Distribution of the cellular uptake of phosphorothioate oligodeoxynucleotides in
      the rat kidney in vivo.
AB  - Previous animal studies have demonstrated that following systemic administration
      phosphorothioate oligodeoxynucleotides (S-ODNs) are primarily excreted by the
      kidneys and that renal tissue levels of S-ODNs exceed that of other organs. Thus,
      the kidney may be an ideal target organ for application of antisense S-ODNs in
      vivo. We examined which cells within the rat kidney have uptake of radiolabeled S
      ODNs following intravenous infusion. A 20-base 35S-ODN was infused into 6 adult
      male Wistar rats. Three animals each were sacrificed 30 min and 4 h after
      infusion. The kidneys were then removed, fixed, and tissue autoradiography was
      performed. Similar results were obtained in both groups. The highest level of
      radioactivity was seen within the proximal tubules. Lower levels of activity were
      seen within the glomerulus, the parietal epithelial cells of Bowman's space, and
      distal tubular cells. Very weak activity was also detected within the cells of
      the loop of Henle and the medullary collecting ducts. These results demonstrated
      that within the kidney S-ODNs were taken up primarily by proximal tubular cells,
      with much lower uptake by cells in other segments of the nephron.

PMID- 9031276
TI  - Magnesium lithospermate B suppresses the increase of active oxygen in rats after
      subtotal nephrectomy.
AB  - Subtotally nephrectomized rats were found to have decreased activities of
      superoxide dismutase (SOD) and catalase, and spin trapping with 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO) showed that the amount of hydroxyl radical in the
      residual kidney tissue was greater than that in normal rat kidney. This indicated
      both direct and indirect involvement of free radicals in renal failure. In
      contrast, rats given magnesium lithospermate B (10 mg/kg body weight) orally for
      30 days after subtotal nephrectomy showed restoration of SOD and catalase
      activities to almost normal levels. Hydroxyl radical, which is highly reactive
      and for which there is no scavenger system in the body, was decreased markedly in
      kidney homogenates obtained from rats given magnesium lithospermate B and in an
      experimental system for hydroxyl radical production to which magnesium
      lithospermate B was directly added. The increased levels of uremic toxins in the
      blood were also low in rats given magnesium lithospermate B. This indicates that
      magnesium lithospermate B helps to inhibit the progression of renal failure by
      scavenging radicals.

PMID- 9031277
TI  - Sneddon's syndrome: a vascular systemic disease with kidney involvement?
AB  - Sneddon's syndrome is a systemic disease characterized by livedo reticularis and
      cerebrovascular disease. Other organs may be involved as well. Typical vascular
      lesions in the skin biopsy and/or digital arteries biopsy can be found. Arterial
      hypertension, cardiac pathology (ischemic disease, myocardial infarction,
      valvulopathy), venous thrombosis and even fetal death are also found sometimes.
      We present a case of Sneddon's syndrome in which typical vascular lesions in the
      kidney were demonstrated for the first time unequivocally confirming the systemic
      nature of this syndrome.

PMID- 9031278
TI  - A comparison between percutaneous and surgical placement techniques of permanent
      peritoneal dialysis catheters.

PMID- 9031279
TI  - Spontaneous rupture of peritoneal catheters.

PMID- 9031280
TI  - Emergency hemodialysis using lactate-buffered dialysate.

PMID- 9031281
TI  - In vivo effect of hydroxyl radical scavenger on methylguanidine production from
      creatinine.

PMID- 9031282
TI  - Hydroxyurea, sickle cell disease and renal transplantation.

PMID- 9031283
TI  - Haematological complications of proguanil in a patient with chronic renal
      failure.

PMID- 9031284
TI  - Budd-Chiari syndrome following pretransplant mononephrectomy in an autosomal
      dominant polycystic kidney disease patient with liver cysts.

PMID- 9031285
TI  - The validity of the criteria to differentiate the origin of hematuria in the
      automated urinary flow cytometer.

PMID- 9031286
TI  - Parent and child cases of IgA nephropathy associated with von Recklinghausen's
      disease.

PMID- 9031287
TI  - Reduction of plasma nitric oxide in a patient with endotoxic shock by
      hemoadsorption therapy.

PMID- 9031288
TI  - Calcitriol may directly suppress bone turnover.

PMID- 9031289
TI  - A case study of inappropriate idiopathic erythropoietin production in a patient
      on regular hemodialysis for 10 years: is beetjuice a factor?

PMID- 9031290
TI  - Low-dose intranasal desmopressin (DDAVP) for uremic bleeding.

PMID- 9031291
TI  - Increased levels of blood angiotensin-converting enzyme in idiopathic
      hypercalciuric renal stone formers.

PMID- 9031292
TI  - Possible association of xanthine dehydrogenase/xanthine oxidase activity with
      nitric oxide in vivo.

PMID- 9031299
TI  - Results of a repeated excimer laser photorefractive keratectomy for myopia.
AB  - BACKGROUND AND OBJECTIVE: As photorefractive keratectomy (PRK) becomes more
      widely used, the incidence of repeated PRK increases. The present study was
      conducted to evaluate results of repeated PRK in view of the meager data on this
      topic. PATIENTS AND METHODS: In this retrospective study, the authors reviewed
      the records of 1028 eyes that had undergone PRK, and analyzed the results of 66
      eyes that required a second PRK for undercorrection according to baseline
      refraction. RESULTS: A second PRK was performed in 6.3%, 13.7%, and 10.1% of low,
      moderate, and high myopes, respectively. The mean refraction 1 year after
      repeated PRK was similar in both myopic groups: less than -1.00 D. Of the low
      myopes, 87.50% had residual refraction within 1 D after 1 year. Of the moderate
      myopes, 88.23% had residual refraction within 1 D after 1 year. All of the low
      myopes achieved uncorrected visual acuity (VA) of 20/25 or better 1 year after
      repeated PRK, compared with 58.82% of the moderate myopes. Loss of best-corrected
      VA never exceeded two lines. CONCLUSION: The overall results of PRK appear to be
      satisfactory.

PMID- 9031300
TI  - Mitomycin-C in laser sclerostomy: benefit and complications.
AB  - BACKGROUND AND OBJECTIVE: The authors studied the effect of topical mitomycin-C
      administration on the maintenance of filter function and intraocular pressure
      (IOP) following laser sclerostomy. PATIENTS AND METHODS: Twenty-six patients with
      a presumed high risk of episcleral scarring were treated intraoperatively with
      topical mitomycin-C (0.5 mg/ml) for 3 to 5 minutes. Their IOPs were monitored for
      at least 2 years. The IOP data of these patients were compared with the results
      for 46 patients who underwent the identical procedure without antimetabolite.
      RESULTS: IOPs below 23 mm Hg were achieved in 70% of the mitomycin-C-treated
      patients. Compared with the non-mitomycin-C group, the rate and duration of early
      postoperative hypotony was significantly increased in the mitomycin-C-treated
      group. CONCLUSION: Mitomycin-C is useful for maintaining successful filter
      function in patients with unfavorable prognoses. However, severe and persistent
      hypotony may occur.

PMID- 9031301
TI  - Combined small-incision cataract surgery and trabeculectomy: a prospective study
      with 1 year of follow-up.
AB  - BACKGROUND AND OBJECTIVE: Small-incision cataract surgery, when performed on
      patients with primary open angle glaucoma, can easily be combined with
      trabeculectomy. PATIENTS AND METHODS: Thirty-six consecutive eyes of 26 patients
      who underwent combined surgery with a follow-up period of 12 months were studied
      prospectively. The first 10 eyes underwent trabeculectomies performed using one
      method (method 1) and the subsequent 26 eyes underwent trabeculectomies performed
      using a slightly different method (method 2). RESULTS: Preoperatively, all 36
      eyes were receiving medication but only 5 had controlled intraocular pressures
      (IOPs) (< 22 mm Hg). Twelve months post-operatively, all 36 eyes had controlled
      IOPs and only 7 needed medication. A significant reduction in IOP occurred with
      each method. There were no significant differences in visual rehabilitation
      between the methods. The major complication was anterior chamber bleeding of
      various degrees. During the follow-up period, two YAG-laser capsulotomies were
      performed. CONCLUSION: The data from combined surgery compare favorably with the
      data from sequential cataract and filtration surgery. Combined surgery could
      probably be performed more often not only for cataract patients with uncontrolled
      glaucoma, but also for patients who cannot tolerate glaucoma medications or who
      have difficulty with the administration of these medications.

PMID- 9031302
TI  - Ocular hypertension after cataract surgery: a comparison of three surgical
      techniques and two viscoelastics.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the incidence and course of ocular
      hypertension after cataract surgery using two different viscoelastics and three
      different surgical techniques. PATIENTS AND METHODS: Thirty-six patients who had
      undergone extracapsular cataract extraction (ECCE), 22 who had undergone
      phacoemulsification (PHACO), and 16 who had undergone manual nucleofragmentation
      (MNF) were randomized to receive either a low-viscosity viscoelastic (LVV) or a
      high-viscosity viscoelastic (HVV) intraoperatively. Post-operative evaluation
      included anamnesis, intraocular pressure (IOP) measurement, and slit-lamp
      examination at 3, 6, 24, and 72 hours and 7 days. RESULTS: The incidence of
      increased IOP over baseline after cataract surgery was 74.3%. The study of both
      viscoelastics revealed a trend for higher IOP during the first 24 hours for
      patients who received HVV (P < .05). Greater differences were observed when
      comparing surgical techniques. Small-incision techniques showed higher mean
      postoperative IOPs, and more severe hypertensions (PHACO 5/22 [22.7%] and MNF
      2/16 [12.5%] vs ECCE 3/36 [8.3%]) (P < .05). CONCLUSIONS: Ocular hypertension is
      a frequent postoperative complication. It is slightly more common when using HVV.
      Small-incision techniques show higher mean postoperative IOPs and more severe
      hypertensions.

PMID- 9031303
TI  - Risk factors for elevated intraocular pressure after the use of intraocular gases
      in vitreoretinal surgery.
AB  - BACKGROUND AND OBJECTIVE: The authors studied the contribution of multiple
      factors, including gas type and concentration, to postoperative intraocular
      pressure (IOP) elevation following vitreoretinal surgery with intraocular gas.
      PATIENTS AND METHODS: One hundred seventy-one eyes of 134 patients were
      retrospectively investigated after vitreoretinal surgery using air, sulfur
      hexafluoride (SF6) (10%-30%), or perfluoropropane (C3F8) (5%-35%). RESULTS: IOPs
      greater than 25 mm Hg occurred in 74 of 171 eyes (43%). Elevated IOP was
      associated with increasing patient age (P < .001), expansile gas concentrations
      (P < .001), use of C3F8 (P = .01), and circumferential scleral buckles (P = .04).
      Most IOP elevations (65 eyes, 88%) occurred within 24 hours and responded to
      aqueous suppression within 24 to 72 hours. CONCLUSIONS: Transient IOP elevation
      is common following vitreoretinal surgery. Although it is responsive to
      treatment, it may pose a risk to some eyes. Prophylactic treatment should be
      considered in high-risk eyes.

PMID- 9031304
TI  - Impact of cultures on management decisions following surgical repair of
      penetrating ocular trauma.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the utility
      of routine bacterial and fungal cultures in the diagnosis of endophthalmitis and
      in the subsequent management of patients following penetrating ocular trauma.
      PATIENTS AND METHODS: The medical records of 70 consecutive patients with
      penetrating ocular trauma for whom intraoperative bacterial and fungal cultures
      had been obtained from the wound, aqueous, vitreous, and/or intraocular foreign
      body (IOFB) were retrospectively reviewed. The incidences of infection among eyes
      with and without a clinical diagnosis of infection were compared. A determination
      as to change in clinical management (change of antibiotic, length of treatment)
      was made. RESULTS: Twenty of 70 patients (29%) had positive cultures of the
      wound, aqueous, vitreous, and/or IOFB. Nine (13%) of the 70 patients were
      diagnosed as having endophthalmitis, based on clinical findings at presentation
      and during the subsequent clinical course. Seven (78%) of these 9 patients with a
      clinical diagnosis of endophthalmitis had positive cultures. The remaining 61
      eyes showed no evidence of clinically apparent infections, despite positive
      cultures from 13 eyes (21%). Microbiologic data derived from the culture results
      influenced the clinical management of all 7 patients with endophthalmitis.
      Culture results (positive or negative) did not alter clinical decisions in eyes
      without clinical evidence of infection. CONCLUSION: Bacterial or fungal cultures
      obtained from the eye in the setting of penetrating trauma often had growth of
      organisms without clinical signs of infection. Positive culture results directly
      influenced management decisions in cases with clinically evident endophthalmitis.
      However, routine intra-operative bacterial cultures did not help to identify
      patients in whom endophthalmitis would develop, nor did they assist in directing
      management decisions in eyes without clinical suspicion of infection.

PMID- 9031306
TI  - Erbium:YAG laser sclerectomy with a sapphire optical fiber.
AB  - BACKGROUND AND OBJECTIVE: Laser sclerectomy may offer advantages to conventional
      glaucoma filtering surgery by minimizing conjunctival manipulation and subsequent
      subconjunctival scarring and by providing easier access to difficult locations.
      It has been theorized that minimizing collateral thermal damage may enhance the
      success rate and reduce complications associated with laser sclerectomy. The
      thermal damage induced by the pulsed erbium:yttrium aluminum garnet (Er:YAG)
      laser is notably less than that of other laser modalities, including
      neodymium:YAG (1.06 microns), Er:YSGG (2.79 microns), holmium: YAG (2.10
      microns), and holmium: YSGG (2.10 microns). A major obstacle to the clinical use
      of the Er:YAG laser has been the lack of an efficient and reliable delivery
      system. The single-crystal sapphire optical fiber has an acceptable attenuation
      rate and favorable characteristics for delivery of the Er:YAG wave-length in a
      clinical setting. MATERIALS AND METHODS: An Er:YAG laser (2.94 microns) focused
      into a 300-micron, single-crystal sapphire fiber was used to create ab-externo
      sclerectomies with varying energy levels and pulse rates in each eye of six
      anesthetized rabbits and six human cadaver eyes. Specimens then underwent
      histopathologic analysis and determination of the thermal damage zone. RESULTS:
      For the rabbit sclerectomies, there was a significant positive correlation
      between energy per pulse and the diameter of the thermal damage zone, which
      averaged 22.0 +/- 12.7 microns for all energy levels. For the human
      sclerectomies, a positive correlation existed between the total energy delivered
      (mJ/pulse x total pulses) and the thermal damage zone, with the mean thermal
      damage zone, being 25.0 +/- 9.0 microns. CONCLUSION: The Er:YAG laser with a
      sapphire optical fiber delivery system is an effective means of creating ab
      externo sclerectomies with minimal thermal damage.

PMID- 9031305
TI  - Retinal findings and characteristics in AIDS patients with systemic Mycobacterium
      avium-intracellulare complex and toxoplasmic encephalitis.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the incidence
      and characteristics of retinal and choroidal manifestations of toxoplasmosis
      and/or Mycobacterium avium-intracellulare complex (MAC) in patients with acquired
      immunodeficiency syndrome (AIDS). PATIENTS AND METHODS: The authors analyzed
      their prospectively collected data and found 120 patients with new retinal
      lesions (group A) that were diagnosed 3 months or longer following the diagnosis
      of MAC and/or toxoplasmic encephalitis. The authors also performed a point
      prevalence study of retinal/choroidal findings in 25 consecutive AIDS patients
      (group B) without known eye disease who had been recently treated for toxoplasmic
      encephalitis and/or disseminated MAC infections. In addition, the characteristics
      of retinochoroidal toxoplasmosis scars in 5 AIDS patients were studied and
      compared with the characteristics of scars in 18 immunocompetent patients.
      RESULTS: In this study the incidence of ocular manifestations of MAC was zero
      (95% confidence interval [CI] 0.0% to 3.8%). Two of 25 patients (8%) (95% CI 1%
      to 26%) in group A and 2 of 11 patients (18.1%) (95% CI 3.3% to 51.8%) in group B
      had toxoplasmic retinochoroiditis. CONCLUSION: In AIDS patients, ocular
      manifestations of toxoplasmosis are more common than ocular MAC. In addition,
      when compared with immunocompetent patients, AIDS patients tend to have
      retinochoroidal scars with less retinal pigment epithelium hyperplasia (1.8+ vs
      3+) (P = .03).

PMID- 9031307
TI  - Delayed reattachment of extraocular muscles in rabbits using thin
      polytetrafluoroethylene.
AB  - BACKGROUND AND OBJECTIVE: The authors attempted to find a way to perform reliable
      delayed suture adjustment so that surgeons can investigate whether delayed
      adjustment actually gives more reliable and stable results. To prevent the
      formation of postoperative adhesions and delay the time of adjustment, the
      authors used polytetrafluoroethylene (PTFE) as a mechanical barrier. MATERIALS
      AND METHODS: PTFE was placed between the free muscle end and the sclera as a
      physical barrier in 16 rabbits. RESULTS: PTFE could delay the adjustment for up
      to 4 weeks after surgery in 4 of 10 eyes in each group. After removal of PTFE,
      adjustment was possible up to 12 weeks because there was no adhesion between the
      muscle and the PTFE. CONCLUSION: Adjustment could be delayed up to 4 weeks in 40%
      of the experimental eyes using PTFE as a physical barrier.

PMID- 9031308
TI  - Indocyanine green angiography of a laser-induced retinal-choroidal venous
      anastomosis.
AB  - A patient with a central retinal vein occlusion and cystoid macular edema whose
      visual acuity was 20/200 was treated with heavy argon laser photocoagulation to a
      peripheral retinal vein. The patient's visual acuity improved to 20/20. An
      indocyanine green angiogram performed 5 months following laser therapy showed
      that a retinal-choroidal venous anastomosis had formed at a point where a large
      retinal vein crossed over a large choroidal vein. Because indocyanine green
      angiography can locate large choroidal veins, it may be helpful in guiding this
      laser treatment.

PMID- 9031309
TI  - Intraoperative recognition of retinal vasculitis in a patient with early lens
      induced uveitis.
AB  - The purpose of this article is to describe a clinical finding not previously
      reported in lens-induced uveitis. An 86-year-old woman was seen by the authors 2
      weeks after she had undergone phacoemulsification surgery complicated by retained
      lens material. A pars plana vitrectomy was indicated. Intraoperatively, retinal
      arteritis and phlebitis were documented in the retina immediately adjacent to the
      lens material. This resolved after removal of the material by vitrectomy. This
      previously unreported finding demonstrates the focal inflammatory effect of the
      retained lens material on the retinal vasculature.

PMID- 9031310
TI  - Nd: YAG laser for Ahmed tube shunt occlusion by the posterior capsule.
AB  - The authors describe the case of a 60-year-old aphakic woman who had suffered
      from glaucoma with uncontrolled intraocular pressure. She was treated by Ahmed
      tube shunt implantation. On the first postoperative day, the intraocular pressure
      was unacceptably high and the tip of the implant tube was seen to be embedded in
      a fold of the posterior capsule, with its opening covered by the posterior
      capsule. The authors used the Nd:YAG laser to cut open the fold of the posterior
      capsule that was covering the tip of the tube, thereby restoring the intraocular
      pressure to normal. To the best of the authors' knowledge, this is the first
      report of a tube shunt occlusion by the posterior capsule resolved by the Nd:YAG
      laser.

PMID- 9031311
TI  - The anatomy of probing and irrigation for congenital nasolacrimal duct
      obstruction.
AB  - In this study, an easily palpable landmark, the supraorbital notch or foramen,
      was used to simplify the localization of the nasolacrimal duct during the probing
      procedure. The notch was palpated in 50 patients of a pediatric clinic. The
      topographic anatomy of the notch in relation to the lacrimal drainage system was
      studied in 10 skulls. The supraorbital notch is a convenient landmark for the
      guidance of a probe into the nasolacrimal canal. This technique should reduce the
      failure rate of probing without the need for infracturing of the lower turbinate
      or silicone intubation.

PMID- 9031312
TI  - A simple surgical treatment for upper lid trichiasis.
AB  - The authors report the results of a simple surgical treatment in 24 lids of 19
      patients. The most common cause of the trichiasis was trachoma (83.3%). The
      operation involved splitting the lid margin, fracturing the tarsal plate, and
      everting sutures. The anatomic success rate was 62.5% and the functional success
      rate was 75%. Recurrent cilia were mostly isolated and symptomatic improvement
      was achieved in all but one patient. The authors conclude that this is a cost
      effective procedure.

PMID- 9031313
TI  - Blinding laser weapons.

PMID- 9031325
TI  - HIV and the 7-transmembrane domain receptors.
AB  - The recent discovery of a chemokine receptor, fusin (fusin/CXCR-4), as the long
      sought human immunodeficiency virus type 1 (HIV-1) coreceptor opened an entirely
      new field of aquired immunodeficiency syndrome (AIDS) research on mechanisms of
      viral entry, tropism and pathogenesis. It was soon followed by the identification
      of the chemokine receptor CCR-5 as the major macrophage-tropic (M-tropic) HIV-1
      coreceptor and the demonstration that other chemokine receptors, CCR-3 and CCR
      2b, also may serve as coreceptors, albeit at somewhat lower efficiency. Very
      recently it was demonstrated that the mechanism of the coreceptor function
      involves the formation of a complex on the cell surface between the HIV-1
      envelope, the primary receptor CD4 and the coreceptor. Thus the prevention of the
      HIV-1 envelope glycoprotein-mediated fusion by the chemokines RANTES, macrophage
      inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta, as well as by the
      recently identified fusin/CXCR-4 ligand, stromal cell-derived factor-1 (SDF-1)
      could be explained by disruption of that complex. Interestingly, the
      identification of the HIV-1 coreceptor CCR-5 not only provided new insights into
      the mechanisms of viral entry and tropism, but also may help in explaining why
      some people with genetic alterations in CCR-5 are protected from HIV-1 infection.

PMID- 9031326
TI  - Interleukin-2 promotes the motility of dendritic cells and their accumulation in
      lung and skin.
AB  - Dendritic cells (DC) play a critical role as antigen-presenting cells in vivo. It
      has previously been shown that DC accumulate in the lung in response to
      parenteral injections of IFN-gamma. In the current paper, we report that rat DC
      express the interleukin-2 receptor (IL-2R) alpha-chain (OX-39) and display
      enhanced motility in response to IL-2 in Boyden chamber and video time-lapse
      microscopy assays. Increased motility was specifically inhibited by pretreating
      DC with OX-39 (anti-IL-2R) but not OX-22 (anti-CD45RC), an isotype-matched murine
      monoclonal antibody. The intratracheal injection of IL-2 increased the number of
      OX-6+ dendritic cells located around pulmonary venules and in the lung
      interstitium. When IL-2 was injected into the footpad of the rat. DC were
      increased around dermal venules at 24 h. This effect was blocked by the
      parenteral injection of anti-OX-39. We conclude that IL-2 is a potent enhancer of
      DC motility and may cooperate with other T helper(h)-1 proinflammatory cytokines
      in attracting DC to sites of inflammation.

PMID- 9031327
TI  - Increased expression of intercellular adhesion molecule 1, CD11/CD18 cell surface
      adhesion glycoproteins and alpha 4 beta 1 integrin in a rat model of chronic
      interstitial lung fibrosis.
AB  - The expression of the intercellular adhesion molecule 1 (ICAM-1), and the
      integrins CD49, CD11b/c, and CD11a (LFA-1 alpha chain) was analyzed in an
      experimental model of pulmonary fibrosis. Adult rats were exposed to 75% oxygen
      during 10 weeks, and to 2.0 mg/kg of paraquat twice weekly. Rats were sacrificed
      at 2 days, and at 2 and 10 weeks after the first injection of paraquat. Lungs
      were fixed in 4% paraformaldehyde and used for histology and
      immunohistochemistry. At 2 days the lungs showed a diffuse inflammation composed
      of a mixed polymorphonuclear and mononuclear cell infiltrate. Afterwards, the
      inflammatory process was predominantly mononuclear, and an increasing fibroblast
      proliferation was observed. Early inflammatory events (48 h) correlated with a
      moderate increased expression of ICAM-1, LFA, and CD11b/c in epithelial cells as
      well as a pronounced expression of ICAM-1 and CD11b/c in macrophages. At 2 and 10
      weeks, there was a progressive increased expression of CD11b/c and ICAM-1 by
      macrophages, as well as of LFA in epithelial cells, and of ICAM-1 and CD49 by
      epithelial and interstitial cells. Lymphocytes showed a slight increased
      expression of LFA at 2 weeks, and of CD49 at 2 and 10 weeks. These results
      suggest that macrophages expressing ICAM-1, CD11b/c, and CD49 are involved in the
      earlier and late phases of the disease whereas fibroblast and epithelial cells
      expressing ICAM-1 and CD49 might play a role in the cell interactions involved in
      the fibrotic phase.

PMID- 9031328
TI  - Adhesion molecules and wound healing in spinal cord injury.
AB  - The purpose of this study was to design and test a model that could identify and
      define which cellular adhesion molecules (CAMs) present on peripheral blood
      leukocytes were depressed in spinal cord injury (SCI) patients. CAMs on
      peripheral blood cells of SCI patients with pressure ulcers were measured by flow
      cytometry and compared with those of age-matched healthy controls and SCI
      patients on physical rehabilitation therapy (PRT) protocols without pressure
      ulcers. The latter patients had normal levels (97%) of lymphocyte function
      associated antigen 1 (LFA-1; CD11a/CD18) and a low incidence of infection. By
      contrast, prior to undergoing rehabilitation therapy, SCI patients with pressure
      ulcers had significantly diminished LFA-1 levels (62%). Very late antigen 4 (VLA
      4; alpha 4 beta 1; 34%) levels (i.e., alpha 4 = 34% and beta 1 = 44%) were
      approximately half those in controls (72%). Expression of alpha 2 and alpha 3 was
      also diminished in patients. Patients receiving PRT after debridement developed
      increased levels of LFA-1 and VLA-4 by the 6th week but alpha 2 and alpha 3
      remained relatively low. These results combined with data from previous studies
      suggest that patients not receiving PRT developed severe pressure ulcers which
      required debridement surgery and healed more slowly due, in part, to reduced
      levels of CAMs.

PMID- 9031329
TI  - Mechanisms of HSP65 expression induced by gamma delta T cells in murine
      Toxoplasma gondii infection.
AB  - We have previously reported that the expression of an endogenous 65-kD heat shock
      protein (HSP65) in macrophages is closely correlated with the protection against
      infection by Toxoplasma gondii in mice, and gamma delta T cells play a critical
      role in the expression of this protein. In this study, we investigated how gamma
      delta T cells contribute to the protection and HSP65 expression. After
      intraperitoneal infection with bradyzoites of the Beverley strain of T. gondii,
      mRNA encoding IFN-gamma and TNF-alpha was detected in the peritoneal gamma delta
      T cells by RT-PCR technique, and macrophages that produced nitric oxide (NO) and
      expressed HSP65 were also detected. Depletion of gamma delta T cells resulted in
      suppression of NO production by macrophages, and it also inhibited HSP65
      expression. HSP65 expression, however, does not appear to be induced by
      stimulation with NO, since treatment with NG-monomethylarginine, an inhibitor of
      NO synthesis, did not attenuate the expression of HSP65. This expression was
      completely suppressed when mice were simultaneously treated with anti-IFN-gamma
      and anti-TNF-alpha although either antibody alone was less effective. The
      synergistic effect of these cytokines was also demonstrated by an in vitro
      experiment, in which peritoneal macrophages were cultured with recombinant IFN
      gamma and TNF-alpha. These results indicate that gamma delta T cells, which
      protect against infection with T. gondii induce the expression of HSP65 by
      secreting IFN-gamma and TNF-alpha and the production of NO, and that the
      expression of HSP65 is independent of inflammatory chemical compounds like NO and
      H2O2.

PMID- 9031330
TI  - HIV-1 disease association with HLA-DQ antigens in African Americans and
      Caucasians.
AB  - Previously, we have shown that CD4 levels in African Americans infected with
      human immunodeficiency virus-1 (HIV-1) were lower than those in Caucasians. To
      determine whether or not HLA type is associated with susceptibility to HIV-1
      infection, we demonstrated serologically that HLA-DQ6(1) and HLA-DQ7(3) were
      associated with HIV-1 infection in both African Americans and Caucasians. The
      present investigation was designed to demonstrate whether or not HLA-DQB1 alleles
      were associated with HIV-1 infection or protection from infection within these
      two ethnic groups. Oligonucleotide typing was employed and results were analyzed
      by chi 2 with Fisher's exact test to compare HLA-DQ marker frequencies in the
      regional control population (98 African Americans, 143 Caucasians) to the disease
      population (n = 52; 30 African Americans and 22 Caucasians). We found a
      statistically significant increased risk of HIV infection associated with HLA
      DQB1*0605 in African Americans, and with HLA-DQB1*0602 in Caucasians. By
      contrast, HLA-DQB1*0603 was associated with protection in Caucasians.

PMID- 9031331
TI  - Protective effect of lidocaine on cell damage in the perfused rat heart.
AB  - The effect of lidocaine (2 mM) on cell damage in the perfused rat heart is
      compared in three experimental protocols: the Ca(2+)-paradox, the O2-paradox and
      perfusion with caffeine. Lidocaine protected against creatine kinase (CK) release
      when perfused throughout or only during the priming stage in all three protocols.
      Lidocaine also protects against CK release in the Ca(2+)-paradox when present
      only during Ca(2+)-reperfusion. Lidocaine protects against myofilament damage in
      the Ca(2+)-paradox but not in the O2-paradox and caffeine protocols, even though
      CK release is inhibited. Analysis of these different effects of lidocaine on the
      priming and full activation stages in the three protocols suggests the sequence
      of the underlying biochemical events of the two separate damage pathways
      associated with the release of cytosolic proteins and the degradation of the
      myofilament apparatus.

PMID- 9031332
TI  - The protective effect of lowered temperature on the oxygen paradox in the rat
      heart.
AB  - The isolated rat heart was completely protected against creatine kinase (CK)
      release in the standard Ca2+ or O2 paradoxes when perfused at 28 degrees C
      instead of 37 degrees C, as previously reported. Hearts subjected to the O2
      paradox at 28 degrees C recovered normal contractile activity, and electron
      microscopy revealed normal, undamaged ultrastructure. The mitochondria remained
      contracted and showed no signs of Ca2+ uptake following a rise in Ca2+
      concentration in the cytosol that would be expected following the prolonged
      period of anoxia. It is concluded that the rise in [Ca2+]i that results from a
      perturbation of Ca2+ homeostasis during anoxic perfusion in the O2 paradox is not
      sufficient to cause either CK release or myofilament degradation which follow
      only on reoxygenation in the second phase of the paradox. Since both the Ca2+ and
      O2 paradoxes are completely protected when the first stage is carried out at 28
      degrees C, it is concluded that the initial activation of the sequence of damage
      events is prevented at this temperature.

PMID- 9031333
TI  - Biological alterations of rat podocytes cultured under basolateral hydrostatic
      pressure.
AB  - In vivo, glomerular visceral epithelial cells (GVEC), or podocytes, are
      morphologically highly differentiated cells which are in close contact with
      adjacent cells by complex interdigitating foot processes. In vitro, the
      dedifferentiated appearance of podocytes hampers investigations on podocyte
      structure and function. Cultured podocytes resemble simple epithelium in several
      ways with apical tight junctions and absence of foot processes. The morphological
      resemblances between GVEC early in embryonic development, in proteinuric diseases
      and in cultured cells are striking, but the mechanisms involved in these
      (de)differentiation processes are poorly understood. A common feature of GVEC in
      these various states of dedifferentiation is their altered exposure to or even
      total lack of hydrostatic pressure, suggesting that this may be one of the
      parameters involved in GVEC differentiation. In this study we investigated
      whether basolateral hydrostatic pressure could affect GVEC biology in vitro. We
      therefore exposed cultured GVEC grown on porous supports to basolateral
      hydrostatic pressure and investigated morphology with scanning and transmission
      electron microscopy, expression of specific podocyte markers and their biological
      responses to a model stimulus, the cytokine IFN-gamma. Morphologically,
      monolayers of pressurized GVEC contained large regions of whirl-like, raised cell
      formations. Individual cells in these formations had a rounded morphology and
      pore-like indentations between adjacent cells were observed. Cell-cell contacts
      were often found more basally and intercellular spaces were widened. Moreover,
      protein expression of pressurized monolayers was altered, as demonstrated by
      regions of cells with decreased keratin expression. Finally, upon exposure to the
      model stimulus IFN-gamma, the pressurized as compared to the control GVEC
      demonstrated a 3-fold increased expression of MHC class II and a strongly
      decreased sensitivity to the toxic effects of IFN-gamma. In conclusion, we found
      several indications that hydrostatic pressure can affect podocyte biology in
      vitro and similar mechanisms may account for podocyte biology in vivo. The
      strikingly altered morphology and biology of pressurized GVEC suggest that this
      culture system can be quite relevant for future studies with cultured GVEC.

PMID- 9031371
TI  - Hopkins Lupus Pregnancy Center: 1987 to 1996.
AB  - This article discusses lupus and pregnancy from experiences at the Hopkins Lupus
      Pregnancy Center. This center has made important strides in the understanding of
      lupus flares, maternal morbidity, and causes of preterm birth and pregnancy loss
      in lupus pregnancy.

PMID- 9031372
TI  - Systemic lupus erythematosus flares during pregnancy.
AB  - Lupus activity during pregnancy has been the subject of much research and debate
      recently. Data point to increased SLE activity during pregnancy. SLE may flare
      during any trimester of pregnancy, as well as in the puerperium; however, flares
      are usually mild, affecting skin and joints, and, unless affecting the kidney, do
      not confer any adverse prognosis on pregnancy outcome. Diagnosis of SLE flares
      can be difficult during pregnancy and must rely on a thorough clinical and
      laboratory assessment. Recent data link sex hormones, particularly prolactin, to
      SLE activity, which may be one explanation for the high frequency of SLE flares
      during pregnancy. No data support the thesis that corticosteroids prevent SLE
      flares during pregnancy, and therefore, prophylactic prednisone should not be
      given routinely. HCQ does seem to be safe for the fetus, however. SLE flares can
      be treated, depending on severity, with NSAIDs or with HCQ, prednisone, or
      azathioprine.

PMID- 9031373
TI  - Neonatal lupus syndromes.
AB  - Congenital heart block is considered to be a model of passively acquired
      autoimmunity, whereby immune abnormalities in the mother lead to the production
      of autoantibodies that cross the placenta and presumably injure the otherwise
      normally developing fetus. The major targets of the maternal immune response are
      the SSA/Ro and SSB/La ribonucleoproteins. Other neonatal abnormalities affecting
      the skin, liver, and blood elements have also been reported to be associated with
      anti-SSA/Ro-SSB/La antibodies in the maternal and fetal circulation and are now
      grouped along with congenital heart block under the heading of the neonatal lupus
      syndromes. This review covers the histopathology, SSA/Ro-SSB/La antigen-antibody
      systems, immunogenetics, clinical manifestations, and diagnosis and management
      strategies of these syndromes.

PMID- 9031374
TI  - Antiphospholipid antibodies in healthy pregnant women.
AB  - This article discusses the prevalence and clinical significance of
      antiphospholipid antibodies (aPL) in the normal, healthy pregnant population.
      Although an increased risk for adverse fetal outcome has been shown in a small
      subset of this population, most pregnancies in aPL-positive mothers have
      successful outcomes. We review the variations in aPL levels during pregnancy and
      consider screening strategies and therapeutic interventions in healthy aPL
      positive pregnant women.

PMID- 9031375
TI  - Antiphospholipid syndrome in pregnancy. Obstetric concerns and treatment.
AB  - To be sure, antiphospholipid antibody syndrome is a protean disease with many
      manifestations, some of which are exacerbated during pregnancy, and some of which
      even lead to its initial diagnosis during pregnancy. Although the best treatment
      during pregnancy is uncertain at this point, and some of the treatments are even
      experimental, there does seem to be a benefit in at least identifying and
      probably treating those with risk factors. If treatment is not instituted with
      heparin, aspirin, or other medical management, at least monitoring for the known
      superimposed disease states, such as intrauterine growth retardation,
      preeclampsia, and fetal loss, should be judicious, with close antenatal
      surveillance.

PMID- 9031376
TI  - Placental pathology in systemic lupus erythematosus and phospholipid antibody
      syndrome.
AB  - Fetal loss is increased in women who meet the Arthritis and Rheumatism
      Association criteria for systemic lupus erythematosus (SLE) and in women who have
      phospholipid antibody syndrome (APS). There are multiple causes for this fetal
      loss, and in patients with SLE, disease activity appears to be an important
      contributing factor. In APS patients, it appears that some individuals will
      experience recurrent fetal loss and will continuously fail to complete pregnancy
      naturally. Placental examination has helped to elucidate some of the pathology
      that may be contribute to this fetal loss and our studies have shown that the
      same pathology is repeated in subsequent pregnancies. Placental examination in
      SLE or APS patients with recurrent fetal loss is vital if we are going to be able
      to determine appropriate therapy to prevent fetal loss.

PMID- 9031377
TI  - Animal models for antiphospholipid syndrome in pregnancy.
AB  - Experimental models for antipospholipid syndrome (APS) have been established
      recently in lupus-prone mice and induced in naive mice. The induction of APS is
      performed by passive infusion or active immunization of antiphospholipid
      antibodies (aPL) or the cofactor beta 2GP-1. High levels of diverse aPL develop
      in the animals in conjunction with clinical manifestations similar to the human
      disease, entailing low fecundity rate, fetal resorptions, thrombocytopenia,
      prolonged activated partial thromboplastin time, and neurological and behavioral
      impairments. The pathogenicity of aPL was confirmed in an in vivo thrombosis
      model. Immunomodulation of APS manifestations and treatment regimens in the
      experimental models are discussed.

PMID- 9031378
TI  - Obstetric management of the high-risk lupus pregnancy.
AB  - With improvements in diagnosis and treatment, the prognosis of patients with
      systemic lupus erythematosus has generally improved in recent years, and
      similarly the outlook for women who become pregnant in the setting of this
      disorder is far more optimistic than it once was. The risk of significant
      morbidity to both the mother and fetus exists, however. Beginning with
      preconception counseling, a careful and thorough approach to the care of the
      patient and cooperation among her various health care providers optimizes the
      chance of a successful pregnancy.

PMID- 9031379
TI  - Scleroderma and pregnancy.
AB  - Pregnancy in systemic sclerosis may be uneventful, with both good maternal and
      fetal outcomes. Because scleroderma is a multisystem disease and complications do
      occur, however, careful antenatal evaluations, discussion of potential problems,
      and participation in a high-risk obstetric monitoring program is very important
      to optimize the best outcome. Because women with diffuse scleroderma are at
      greater risk for developing serious cardiopulmonary and renal problems early in
      the disease, they should be encouraged to delay pregnancy until the disease
      stabilizes. All patients who become pregnant during this high-risk time should be
      monitored extremely carefully. Although there are some suggestions that there are
      increases in infertility and miscarriages before disease onset, recent studies
      show that these issues probably do not have major impact for women with
      established scleroderma who plan to become pregnant. The high risk of premature
      and small infants may be minimized with specialized obstetric and neonatal care,
      however. Renal crisis in scleroderma is the only truly unique aspect of these
      pregnant, which, unlike blood pressure elevation in nonscleroderma pregnancies,
      must be treated aggressively with ACE inhibitors. Other pregnancy problems may
      not be unique to scleroderma, but because it is a chronic illness, any
      complication carries higher risks for both mother and child. Careful planning,
      close monitoring, and aggressive management should allow women with scleroderma
      to have a high likelihood of a successful pregnancy.

PMID- 9031381
TI  - Obstetric complications and rheumatic disease.
AB  - This article summarizes common fetal and maternal complications of pregnancy and
      emphasizes special problems in women who have systemic lupus erythematosus,
      rheumatoid arthritis, systemic sclerosis, dermatomyositis, polymyositis, and
      Sjogren's syndrome. Joint management of pregnancies in these women requires an
      understanding of the obstetric management of the complications. Pathophysiology
      and treatment options for preterm-labor, preterm premature rupture of membranes,
      abnormal fetal growth, and hypertensive disorders of pregnancy are reviewed.

PMID- 9031380
TI  - Immunosuppressive drug use during pregnancy.
AB  - Women with rheumatic diseases frequently need treatment throughout pregnancy and
      lactation. Physicians must confront the dual challenge of monitoring the possible
      effects of the underlying maternal disease and the medications on both mother and
      child. It is essential that the maternal disease be well controlled before,
      during, and after pregnancy to ensure the best possible outcome for the mother
      and child. Corticosteroids have been used extensively and safely in pregnant
      patients with systemic lupus erythematosus and rheumatoid arthritis; there have
      been no reports of congenital malformations in the exposed infants. There is
      considerable experience using azathioprine during pregnancy if the maternal
      condition requires use of a cytotoxic drug; there has been no increased risk of
      congenital malformations in the exposed infants. There is limited information on
      the safety of other medications, including 6-mercaptopurine, cyclophosphamide,
      and cyclosporine. Methotrexate is contraindicated during pregnancy, and
      chlorambucil should be avoided because there are other effective
      immunosuppressive agents available for use. Corticosteroids (prednisone and
      methylprednisolone) can be used safely during lactation. All other
      immunosuppressive medications, azathioprine and 6-mercaptopurine, chlorambucil,
      cyclophosphamide, cyclosporine, and methotrexate, are contraindicated during
      lactation.

PMID- 9031382
TI  - Thrombocytopenia in pregnancy.
AB  - Thrombocytopenia is a common finding in normal pregnancy. The introduction of
      routine automated complete blood counting has clearly documented this. In the
      past, these patients would go undetected and be spared unnecessary testing,
      procedures, or medications. This article reviews the common causes of
      thrombocytopenia and offers criteria on which the diagnosis of clinically
      significant thrombocytopenia can be made. In addition, we will discuss
      therapeutic approaches to manage patients with pathologic thrombocytopenia.

PMID- 9031391
TI  - Food, hunger and the market economy.

PMID- 9031383
TI  - Pregnancy and rheumatoid arthritis.
AB  - Amelioration of rheumatoid arthritis (RA) occurs in about three quarters of
      pregnancies. Most women who improve experience initial relief in the first
      trimester. RA almost invariably recurs within 3 to 4 months of delivery. The
      effect of pregnancy upon the risk of first developing RA is similar in some
      respects but also differs from that observed in women with established disease.
      Analogous to women with established disease, the chance of a woman first
      developing RA is significantly reduced during pregnancy but increased in the
      first year post partum; thereafter risk is decreased. There is no indication of
      any adverse effects of RA on pregnancy outcome. Although limited, some
      medications can be used during pregnancy and during lactation without
      jeopardizing the well-being of the fetus.

PMID- 9031392
TI  - Malaria: cost to India and future trends.
AB  - A study of the economic loss due to malaria and its future trends revealed that
      malaria in India was responsible for economic loss between US$ 0.5 to 1.0 billion
      annually. The study also brought out that malariogenic potential of the country
      is increasing, and new malaria paradigms have been established requiring new
      approaches for its control. Unless this trend is checked losses due to malaria
      will increase in the coming decades. Effective malaria control requires immediate
      remedial measures to prevent environmental degradation conductive to vector
      proliferation; and renewed attack on malaria based on local epidemiological,
      entomological and social determinants. The first requirement for such an action
      is a reliable data base, both on the malariometric indices and the causative
      factors. Research therefore should be intensified to fill the gaps, generate new
      knowledge, disseminate malaria information as widely as possible and provide
      training for success in malaria control by the implementation of the global
      malaria control strategy.

PMID- 9031393
TI  - Quinine-tetracycline for multidrug resistant falciparum malaria.
AB  - Plasmodium falciparum in Southeast Asia is highly resistant to chloroquine and
      sulfadoxine/ pyrimethamine. Quinine-tetracycline has been used as a second line
      treatment for uncomplicated falciparum malaria, but duration of treatment varies
      from place to place. The 7-days course of this combination has been shown to be
      very effective. However, due to the cinchonism adverse effects, the patient
      compliance has not been satisfactory. We have evaluated the efficacy of a 7-days
      course of tetracycline in combination with either 5 or 7-days course of quinine.
      Ninety male Thai patients who were admitted to the Bangkok Hospital for Tropical
      Diseases were randomized to receive tetracycline 250 mg qid for 7 days in
      combination with either quinine 600 mg tid for 5 days (Q5T7; group A) or quinine
      600 mg tid for 7 days (Q7T7; group B). The patients were hospitalized for 28
      days. Patients in both groups had a comparable initial response to treatment,
      with the clearance of fever and parasites within 4 days. There were 46 and 40
      patients in group A and B, respectively, who completed the 28 day of follow-up.
      The cure rates were 87 and 100%, respectively for group A and B. No serious
      adverse effects were found in either group; transient nausea, vomiting and
      tinnitus were common findings. The incidence of adverse effects was not different
      between the two groups. The results from the present study suggest that a short
      course treatment of quinine (Q5T7) had significantly decreased the cure rate. In
      areas with quinine resistant falciparum malaria, a full course of 7-days quinine,
      in combination with 7-days course of tetracycline is recommended for hospital
      treatment. However, an alternative shorter course of antimalarials is suggested
      for home treatment.

PMID- 9031394
TI  - Artemether-pyrimethamine in the treatment of pyrimethamine-resistant falciparum
      malaria.
AB  - In vitro susceptibility and clinical response of multidrug resistant Plasmodium
      falciparum to the combination artemether-pyrimethamine were evaluated in patients
      with acute uncomplicated falciparum malaria. Sixty patients were randomized to
      receive 3 oral regimens of the combination artemether-pyrimethamine as follows:
      Regimen-I: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then
      placebo on the two consecutive days; Regimen-II: artemether (300 mg) plus
      pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus
      pyrimethamine (50 mg) on the second day, and placebo on the third day; Regimen
      III: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then
      artemether (150 mg) plus pyrimethamine (50 mg) on the second and third days. All
      patients had a rapid initial response to treatments with 95% of parasitemia being
      cleared within the first 24 hours. PCT24hours and PCT48hours were similar among
      the three drug regimens (11 vs 4, 6 vs 12, and 9 vs 11 patients for a 1-day, 2
      day, and 3-day combination regimen, respectively). Fever was cleared within 48
      hours in all patients in either group. Transient mild nausea, vomiting and loss
      of appetite were found in a few patients during the first 2 days of treatment.
      Seven patients did not complete the 28 day follow-up period (5 vs 2 in a 1-day vs
      2-day regimen), the reason for withdrawal was not associated with drug-related
      adverse effects. Only 53 patients were therefore qualified for the efficacy
      assessment. There was 15, 13 and 5 patients in a 1-day, 2-day and 3-day
      combination regimens, respectively, who had reappearance of the parasitemia
      between days 11 and 21. The cure rates of the 3 treatment groups were
      statistically significantly different (0, 27.8, and 75% for a 1-day, 2-day and 3
      day combination regimen, respectively). Two patients developed P. vivax malaria
      on days 20 and 24. All of the isolates were highly resistant to pyrimethamine,
      with MIC of 10(-5) M. There is potential advantage of this combination therapy in
      reducing the dosage and treatment period of artemisinin derivative, which is
      therefore likely to improve complaince in clinical practice. The use of a 3-day
      combination regimen (300 mg artemether plus 100 mg pyrimethamine on the first
      day, then 150 mg artemether plus 50 mg pyrimethamine on the second and third
      days) seems to be a good alternative regimen to sulfadoxine/ pyrimethamine in
      areas where P. falciparum is sensitive to pyrimethamine eg in Africa.

PMID- 9031395
TI  - Changes in Neotricula beta-aperta population density following construction of
      the Pak Mun Dam in northeast Thailand, with implications for the transmission of
      schistosomiasis.

PMID- 9031396
TI  - Costs, benefits and operational implications of using quantitative techniques to
      screen for schistosomiasis haematobium in Egypt.
AB  - The official strategy for schistosomiasis control in Egypt relies on individual
      case detection and treatment. Screening for Schistosoma haematobium has
      traditionally involved urine sedimentation which shows whether or not eggs are
      present in the urine, thereby providing only a qualitative assessment of
      infection status. Recently the Ministry of Health introduced the nucleopore
      filtration technique into a few villages to assess its applicability for broader
      use in areas where S. haematobium is endemic. This method gives an indirect
      quantitative measure of morbidity in terms of egg counts/10 ml urine. The overall
      purpose of this study was to provide rapid feedback to the Ministry on the likely
      implications of expanding the use of the filtration technique by examining the
      benefits, costs and operational problems that may be involved. From 2 villages in
      Giza Governorate, systematic random samples were taken from the general
      populations and from schools. Each selected person provided a urine specimen on
      which the two diagnostic techniques were performed. Filtration offered no
      additional benefits over sedimentation in terms of defining if a person was
      infected or not, with sensitivities ranging from 59.6%-75% for filtration and
      from 60%-73.1% for sedimentation. The additional non-labor costs of using the
      filtration technique in the two villages were calculated and showed that, if
      extended to all rural health units in Egypt, the Ministry would need to find an
      additional 31.6 million pounds (US$9.5 million) each year. A number of
      operational problems would also be involved in the wider application of the
      technique.

PMID- 9031397
TI  - Socioeconomic and behavioral factors affecting the prevalence of geohelminths in
      preschool children.
AB  - The aim of this study was to examine the relationship between the prevalence of
      geohelminth infections in preschool children living in an urban slum area in Sri
      Lanka and parental education, socioeconomic status, the use of anthelmintics, and
      beliefs regarding these helminths. Between October 1992 and February 1993, stool
      samples were collected from preschool children (< or = 60 months of age) in the
      Mahaiyyawa area, Kandy, Sri Lanka, and examined using direct smears and a
      concentration technique. Stool samples which were found to be positive for
      helminth ova were also examined using the modified Kato-Katz technique. A
      pretested questionnaire was administered to the mothers or principal caretakers
      of the children from whom stool samples were obtained to assess parental
      education, socioeconomic status of the family and knowledge, attitudes and
      practices related to intestinal parasites, particularly geohelminths. Stool
      samples from 307 children were examined; 81 (26.4%) were positive for geohelminth
      ova. Roundworm infections predominated, and were seen in 73 of the 81 (90.1%),
      either alone or together with whipworm and/ or hookworm infections. All
      infections were of mild to moderate intensity. Questionnaires were administered
      to the mothers/principal caretakers of 208 children. Mothers/caretakers of 91
      children (45%) claimed that the child was on regular anthelmintics. As the
      educational level of the mother/caretaker improved, the prevalence of geohelminth
      infections in the children declined (chi-square for linear trend = 8.19, p =
      0.004). However, there was no significant correlation between prevalence of
      infections and paternal educational levels. Prevalence also tended to increase as
      the socioeconomic class declined (chi-square for linear trend = 4.899, p =
      0.026). Another finding of note in this study was the widespread ignorance and
      misconceptions regarding geohelminth infections among carers.

PMID- 9031399
TI  - Vitamin B1, B2 and B6 deficiency in primary school children infected with
      hookworm.
AB  - One thousand and seven hundred thirty-six school children from two districts in
      Nakhon Si Thammarat Province were screened for hookworm infection using the Kato
      Katz stool examination technic. Two hundred students who have at least 2,000 eggs
      per g of stool were recruited into the program. The students were divided into
      six groups: groups 1, 2 and 3 were from Tha Sala district while groups 4, 5 and 6
      were from Ronpibul district. Three milliliter blood samples were obtained from
      the cubital vein of each subject and were evaluated for erythrocyte transketolase
      activity (ETK) for vitamin B1, erythrocyte glutathione oxidoreductase activity
      (EGR) for vitamin B2, and erythrocyte aspartate aminotransferase activity (EAST)
      for vitamin B6. The school children were divided into three groups: those
      infected only with hookworm, those with both hookworm and Trichuris trichiura,
      and those whose stools show no parasite eggs. The results show that 10-20% of the
      school children are vitamin B1 deficient, about 40% to 80% are vitamin B2
      deficient, and about 14% to 23% are vitamin B6 deficient. No correlation could be
      made between vitamin deficiencies and parasitic infection.

PMID- 9031398
TI  - Intestinal sarcocystosis in Thai laborers.
AB  - To determine the prevalence of Sarcocystis and other intestinal parasites in Thai
      laborers who were going abroad for work, stool examinations of 362 asymptomatic
      laborers were studied. The four most frequently parasites found in stool were
      Sarcocystis sp (23.2%), Opisthorchis viverini (40.3%), hookworm (21.5%), and
      Strongyloides stercoralis (14.1%). Giardia intestinalis (5.2%), Entamoeba coli
      (1.7%), Endolimax nana (2.5%), Blastocystis hominis (4.1%), Echinostoma sp
      (3.6%), Trichuris trichiura (0.3%), Taenia sp (1.7%), Hymenolepis nana (0.6%),
      and Enterobius vermicularis (0.3%) were present at low rates. Sarcocystis were
      frequently found in male laborers (83.3%) (p < .01). The laborers from
      northeastern Thailand (n = 278) had a higher prevalence (26.6%) of Sarcocystis
      infection (p < .01). This study shows that Thai laborers, particularly from
      northeastern Thailand, are commonly infected with intestinal parasites. The high
      prevalence rates of Sarcocystis and other intestinal parasites in this study were
      indicative of the local habit of eating raw beef and pork, poor living
      conditions, and low levels of hygiene in Thai laborers. Sarcocystosis could be a
      significant food-borne zoonotic infection in Thailand.

PMID- 9031400
TI  - Spargana infection of frogs in Malaysia.
AB  - Frogs caught from two States (Selangor and Langkawi) in Malaysia were examined
      for spargana of Spirometra sp. Infected frogs usually show no marks of infection
      but some had swelling and bleeding at the infection site. The size and weight of
      the infected frogs did not correlate with the infection status. The infection
      status in relation to human health is discussed.

PMID- 9031401
TI  - Seroprevalence of Sarcoptes scabiei var canis antibodies among aborigines in
      peninsular Malaysia.
AB  - The Aborigines or Orang Asli in Peninsular Malaysia who are still seminomadic are
      known to have a close association with dogs. In this study, enzyme-linked
      immunosorbent assay (ELISA) was used to detect anti-Sarcoptes scabiei var canis
      antibodies in this community as a measure of exposure to the mite. Out of 312
      Orang Asli tested, 24.7% were positive for polyvalent anti-Sarcoptes antibodies.
      No significant difference was found between the positive rates in males (26.1%)
      and females (23.6%). Only 1.9% were positive for IgA and none was positive for
      IgE anti-Sarcoptes antibodies. Since there were very few patients with clinical
      manifestation of scabies, there is a possibility that continuous exposure to the
      dogs mite confers cross-protective immunity in the community against human
      scabies.

PMID- 9031402
TI  - Ultrastructural characteristics of liver fluke associated human
      cholangiocarcinoma cell lines.
AB  - The ultrastructure of a cholangiocarcinoma cell line (HuCCA-l) originally
      established from an intrahepatic bile duct tumor of a patient seropositive for a
      liver fluke infection was studied by scanning (SEM) and transmission (TEM)
      electron miscroscopy. With the SEM, the surface of HuCCA-1 cells were found to be
      covered with microvilli. The size of these microvilli varied from cell to cell
      and they were irregularly distributed. The TEM clearly revealed the presence of
      cytokeratin filaments, an intracytoplasmic lumen, tight junctions at the apices
      and desmosomes at the lateral surfaces of neighboring cells, all of which are
      characteristics of adenocarcinoma cell origin. However, the tumor mass that
      developed in a nude mouse following subcutaneous injection of these cells was
      found to exhibit some morphological changes. Specifically, about 20-30% of the
      tumor cells, particularly those lining the base of the tumor tubules, exhibited
      electron dense tonofilaments typical of squamous cells. However, this alteration
      was reversible as the cell line (HuCCA-1Nu) derived from this nude mouse-passage
      did not exhibit any characteristics reminiscent of squamous cells. These
      observations are consistent with those occasionally found in human cases reported
      previously by other investigators. Altogether, the data showed that squamous
      transformation of adenocarcinoma cells can occur under appropriate conditions. It
      further showed that reversion to adenocarcinoma cells can occur when the
      microenvironment is changed.

PMID- 9031403
TI  - Pyruvate: ferredoxin oxidoreductase from Entamoeba histolytica recognized by a
      monoclonal antibody.
AB  - A mouse monoclonal antibody, Eh208C2-2 MAb, raised against whole cell antigens of
      Entamoeba histolytica trophozoites of the pathogenic strain HM-1: IMSS and
      polyclonal antisera (PAb) against membrane antigens of E. histolytica
      trophozoites of strain HTH-56: MUTM were screened against a cDNA library of the
      pathogenic strain, SFL3. The monoconal antibody detected many phage plaques
      expressing an E. histolytica protein. The DNA sequence encoding the protein was
      approximately 55% identical, over 1,100bp, to Trichomonas vaginalis pyruvate:
      ferredoxin oxidoreductase (PFOR) and pyruvate: flavodoxin oxidoreductase from
      Klebsiella pneumoniae, Anabaena variabilis and Enterobacter agglomerans. Two of
      seven clones detected by mouse polyclonal antisera also encoded this protein. Two
      others encoded Entamoeba Hsp70, another encoded Entamoeba alkyl-hydroperoxide
      reductase and the remaining two were unidentified sequences. Entamoeba PFOR is an
      abundant, antigenic protein which may be a useful target for the development of
      protective host immune responses against invasive amebiasis.

PMID- 9031404
TI  - Comparative surface ultrastructure of adults and eggs of Gnathostoma obtained in
      Japan.
AB  - As limited studies have been done on surface morphology of Gnathostoma, adult
      specimens and eggs of four kinds of species in Japan were compared by scanning
      electron microscopy. Worms had a subglobular head-bulb which was armed with 7-10
      rows of cephalic hooks. Mutidigitate cuticular spines were spaced unevenly on
      transverse cuticular striations on the anterior half of the body. The lengths of
      the spines were variable with tridentate spines longer than bidentate ones, These
      tridantate spines became one of the species specific characteristics. The
      posterior half of the bodies of G. doloresi and G. hispidum were covered densely
      with long unidentate spines which were gradually shorter towards the posterior
      ends. Ventral sides of male terminals had different shape of papillae which so
      called small and caudal ones in species. Eggs recovered from the uteri of female
      worms were covered with cuticular pits of different sizes, shapes and depths in
      species.

PMID- 9031405
TI  - The newly discovered non A-E hepatitis viruses.
AB  - Two biotechnology companies have recently announced the discovery of 4 new
      hepatitis viruses, provisionally named HGV and GBV agents (GBV-A, GBV-B, and GBV
      C). Using a molecular biological approach, the genomes of these viruses were
      identified from non-A-E hepatients patients who had no markers to any previously
      known hepatitis viruses. The new viruses are members of family Flaviviridae, and
      are closely related to hepatitis C virus (HCV). Preliminary studies show that the
      prevalence of GBV agents and HGV are alarmingly high in blood donors in the
      United States, Europe, Africa and Japan. The viruses are transmitted
      parenterally, similar to HCV and hepatitis B virus (HBV), Chronic infection is
      common and can lead to cirrhosis. Some chronic hepatitis cases caused by these
      viruses respond to interferon treatment. The viruses can coinfect with HCV and/or
      HBV. A number of questions about these new viruses remain to be answered,
      including the magnitude of the problems, clinical significance, mode of
      transmission and populations at risk, as well as the appropriate treatment.

PMID- 9031406
TI  - A non-invasive assessment of hepatitis B virus carrier status using saliva
      samples.
AB  - A non-invasive testing method to determine hepatitis B virus (HBV) carrier status
      in pregnant women was evaluated. Paired serum and saliva samples were collected
      and assessment of hepatitis B markers were performed. Of the 502 women enrolled,
      5.6% (28/502) of their sera were found to be positive for HBV surface antigen
      (HBsAg). Assessment of 28 HBsAg seroreactive and 200 HBsAg sero-non-reactive
      paired saliva samples showed that 17 saliva contained HBsAg. Fourteen of the
      saliva reactive samples were matched to the serum reactive samples (50%
      sensitivity); and 3 saliva samples were positive for HBsAg among 200 subjects
      seronegative for HBsAg (98.5% specificity). Seven of the 28 HBsAg positive sera
      were found to be reactive for HBV envelope antigen (HBeAg) (25%). One of seven
      HBeAg seroreactive and 16 HBeAg seronegative paired saliva samples tested were
      non-reactive for HBeAg. This report found a non-invasive saliva testing method to
      be a possible alternative approach for determining chronic HBV carrier status if
      the sensitivity of the test can be improved.

PMID- 9031407
TI  - Clinico-pathological predictive factors of response to interferon therapy in
      chronic hepatitis C.
AB  - We performed a clinico-pathological study to determine which pre-treatment
      factors could predict the response to interferon (IFN) therapy in 55 Japanese
      patients with chronic hepatitis C. Responses to the IFN therapy were evaluated as
      sustained response, relapse and non-response by the presence or absence of serum
      hepatitis C virus (HCV) RNA during the course of treatment and at least 6-months
      post-treatment. The numbers of sustained response, relapse and non-response were
      16 (29.0%), 25 (45.5%) and 14 (25.5%), respectively. Eight out of 16 sustained
      response cases (50%) showed HCV genotype III. Eight among 10 patients with HCV
      genotype III (80%) were sustained responders. HCV genotypes were found to be
      correlated with the response to the IFN therapy (p < 0.0001). None of the
      histological features, the types of the IFN therapy and other clinical factors
      showed significant differences. These findings suggest that outcome of the IFN
      therapy in chronic hepatitis C can be predicted by a virological factor, and that
      HCV genotype III is a useful predictor of a favorable outcome.

PMID- 9031408
TI  - Seroepidemiology of human herpesvirus 6 in a population seen in the University
      Hospital, Kuala Lumpur, Malaysia.
AB  - Sera from healthy donors and patients stored over a period of 2 years, aged 1 to
      83 years, were examined for reactivity to human herpes virus 6 (HHV-6) by the
      standard indirect immunofluorescence assay (IFA). Of the 600 serum specimens
      screened, 502 showed positive reactivity to HHV-6. This gives an overall
      seropositive rate of 83.7%. There is no significant difference in the overall
      positive rate between the ethnic groups (Chinese, Malays, Indians) (chi 2 = 0.35
      df = 2 p > 0.05). However, there is significant difference in the positive rates
      at the extreme age groups of 1 year as well as 61 years and above. From birth up
      to below 1 year of age, the seroprevalence rate was 82%. At one year of age the
      positive rate decreased to 66% before gradually rising so that the percentage
      seropositivity of 6 to 10 years old becomes similar to that in older children and
      adults (11 to 40 years). The positive rate then starts to decline after 40 years
      of age. Using a standardized scoring system, the corresponding antibody titer was
      found to be high in the very young population and starts to decline after the age
      of 15 years. This suggests that in our population group, primary infection occurs
      mainly in the pediatric age group. It also accounts for the low positive rate in
      the age group of 61 years and above, as by then the titer had fallen to the level
      below the detection limits of the assay system.

PMID- 9031409
TI  - Frequency and risk of HIV infection among men attending a clinic for STD in
      Chiang Mai, Thailand.
AB  - A prospective study was conducted in the Chiang Mai Sexually Transmitted Diseases
      Clinic to determine the frequency of HIV seroconversion among men following high
      risk sexual contacts and to establish risk factors for HIV infection. HIV
      antibodies were detected in 26 out of 150 men on the initial recruitment with a
      seroprevalence rate of 21%. Among 124 initial HIV negative subjects; 100, 77, 68,
      and 55 subjects were followed for 2, 4, 12, and 24 weeks, respectively. One
      subject had HIV seroconversion documented with the rate of 1.0% (1/100, 95%
      confidence interval [CI] = 0.03-5.4%). Logistic regression analysis found
      significantly independent associations of HIV prevalence with prostitute visits
      at least once a month (OR = 3.6, 95% CI = 1.2-10.9), and with cigarette smoking
      (OR = 3.5, 95% CI = 1.2-10.5). Intensive health education should be elucidated to
      decrease the high rate of HIV infection among this population.

PMID- 9031410
TI  - Risk factors for neonatal Klebsiella septicemia in Srinagarind Hospital.
AB  - Three years' data were analysed to assess the risk factors for neonatal
      Klebsiella septicemia in Srinagarind Hospital. The incidence of Klebsiella
      septicemia was 4.1 per 1,000 livebirths or 5.2 per 100 discharged infants. Eighty
      two per cent of infected cases were low birth weight infants and 67.7% were born
      prematurely. From multivariate analysis, the risk factors were endotracheal
      intubation (OR 31.57, 95% CI 289-343.82) and central venous catheterization (OR
      16.99, 95% CI1.15-250.37). The overall mortality rate was 67.7%. Periodic review
      and continuous reinforcement of infection control policies in the neonatal unit
      are of paramount importance to decrease the incidence of nosocomial infection and
      successful control of outbreaks as well.

PMID- 9031411
TI  - Risk factors of acute lower respiratory tract infections in children under five
      years of age.
AB  - This study attempted to identify the determinants of acute lower respiratory
      tract infections (ALRI) among children under five years of age, by comparing
      hundred children hospitalized with ALRI with a control group. Data on socio
      demographic, biological and environmental characteristics were collected by
      interviewing mothers and anthropometric measurements were carried out to assess
      the nutritional status of the children. Risk of disease in the presence of each
      exposure was calculated in the univariate analysis and the best explanatory
      variables among them were identified in the multivariate analysis. The following
      variables were found to increase the risk of ALRI: (1) history of wheezing, (2)
      low birth weight, (3) passive smoking, (4) male sex, (5) delivery by cesarean
      section (6) sharing of sleeping space, (7) not being exclusively breast fed upto
      the completion of four months, (8) stunting, (9) having pets. The findings
      highlight some simple strategies which would help in prevention of ALRI.

PMID- 9031412
TI  - Multifactorial pathogenic mechanisms of Burkholderia pseudomallei as suggested
      from comparison with Burkholderia cepacia.
AB  - With the purpose to elucidate the pathogenesis of disease due to Burkholderia
      pseudomallei some biological and biochemical properties of this species were
      studied in comparison with B. cepacia, since the difference in the level of
      virulence between the two species is remarkable despite of their toxonomic
      closeness. B. pseudomallei was distinct from B. cepacia in the capability to grow
      under anaerobic conditions, with positive nitrate respiration, excretion of high
      molecular polysaccharides into liquid culture, and cytotoxicity against cultured
      tissue cells. From these observations together with our previous finding that B.
      pseudomallei can grow and survive in an acidic environment, we suggest
      multifactorial mechanisms for the pathogenesis of melioidosis due to B.
      pseudomallei.

PMID- 9031413
TI  - Salmonella enteritidis outbreak in Thailand: study by random amplified
      polymorphic DNA (RAPD) analysis.
AB  - An outbreak of Salmonella enteritidis in Thailand was reported in 1990. The
      majority of isolates were found in chicken and human throughout the country. The
      continuation of a high rate of spreading which is presently continuing prompted
      us to investigate possible clonal involvement in the outbreak. One hundred and
      twenty five isolates of S. enteritidis which were isolated between 1990-1993 were
      clonally identified by the technique of Random Amplified Polymorphic DNA (RAPD)
      analysis. Eight profiles were found indicating the presence of 8 clones,
      designated no. 1-8. The predominant clone was profile no. 4 which was encountered
      in 93.6% of tested isolates while the rest of the profile comprised only 0.8
      1.6%. The predominant clone was distributed mainly in isolates from chickens and
      humans which is suggestive that the profile no. 4 is the major clone involved in
      this outbreak and that chickens were the source of S. enteritidis infection. The
      information from the Microbiology Laboratory at Ramathibodi Hospital revealed
      that nearly 40% of S. enteritidis were isolated from blood specimens. This may
      reflect the invasiveness of S. enteritidis in Thailand. We concluded that the
      outbreak involved the single clone, RAPD profile no. 4 which may disperse
      dominantly during the epidemic.

PMID- 9031414
TI  - Hemolysins and plasmid profiles of Vibrio parahaemolyticus.
AB  - Forty clinical isolates of Vibrio parahaemolyticus were studied for the
      production of the thermostable direct hemolysin (TDH), and the TDH-related
      hemolysin (TRH) including the respective encoding genes, tdh and trh. The
      presence of TDH and its encoding genes were found amongst 95% of the strains,
      whereas the TRH was absent amongst these isolates. Thirty-two isolates were found
      to be plasmid-free, whereas eight isolates possessed plasmids with sizes ranging
      from 2.4 > or = 23 kb. Using a DNA probe coding for the homologous region of the
      tdh and trh, it was found that the tdh genes were present on the chromosomal DNA.

PMID- 9031415
TI  - Characterization of Aeromonas hydrophila: a comparative study of strains isolated
      from diarrheal feces and the environment.
AB  - Thirty-five strains of Aeromonas hydrophila isolated from feces of diarrheal
      patients and from the environments were collected from Thailand and Japan. The
      physiological, biochemical, and serological characteristics, antibiotic
      resistance patterns and cell surface-related properties were compared. The
      diarrheal and environmental isolates of A hydrophila were found to be remarkably
      consistent in general culture and biochemical characteristics, with the exception
      of the reaction to D-arabinose in which the diarrheal strains were positive and
      environmental strains were negative. The plasmid patterns and cell surface
      related properties of the environmental and diarrheal isolates were different.
      All strains produced Vero cell cytotoxin, hemolysin and lecithinase at 37
      degrees, 30 degrees and 15 degrees C. In contrast, 83% of the environmental
      strains produced these virulence factors even at 4 degrees C. All strains
      indicated almost uniform susceptibility to the 16 antibiotics tested. Variations
      were found in the plasmid profile, toxin production in relation to the
      differences of temperature and cell surface-related properties of the strains.
      These variations between the clinical and environmental isolates could have
      potential as epidemiological markers for the sources of strains.

PMID- 9031416
TI  - ELISA-based colorimetric detection of Rickettsia tsutsugamushi DNA from patient
      sera by nested polymerase chain reaction.
AB  - A rapid diagnostic system for scrub typhus was established using colorimetric
      detection of nested polymerase chain reaction (PCR). This system relied on
      binding the amplified DNA via a sequence in one of oligodeoxyribonucleotide to
      the DNA-binding protein GCN4 coated on the well of a micotiter dish. The primer
      pairs used for the nested PCR were designed on the basis of the homologous
      nucleotide sequence of the gene that encodes the 56 kDa antigen of serovariants.
      With this colorimetric PCR, diagnosis can be performed easily from serum samples
      of patients before the antibody titer increases or in the early stage of the
      disease. Furthermore, these positive results are able to be confirmed by
      pathogenic isolation.

PMID- 9031417
TI  - Brackish water mosquito problem of Vypeen Island, Cochin, Kerala.
AB  - A preliminary study has shown that the marshy terrain and brackish water bodies
      associated with mangrove forests contributed profuse breeding of mosquitos in
      Vypeen island, causing a severe menace to the island population. A total of 14
      species belonging to four genera viz, Aedes, Anopheles, Armigeres and Culex was
      recorded from different habitats. Culex sitiens was found to be the predominant
      mosquito in all the perennial breeding habitats. The extent of different habitats
      in the production of mosquitos, and its possible abatement, using environmental
      and/or biocontrol methods are discussed.

PMID- 9031418
TI  - Effects of Brugia malayi infection on the survival of Anopheles sinensis.
AB  - Effect of different numbers of infecting Brugia malayi on the survival of
      Anopheles sinensis were quantitatively studied in our laboratory. Four groups of
      healthy adult female mosquitos were tested. They were named G-0, G-1, G-2 and G
      3, in which the numbers of microfilariae (mf) infecting per mosquito were 0, 5,
      10 and 50, respectively. The experimental infection was conducted by inoculating
      the mf into the bodies of mosquitos through the neck membrane with a
      microinjector. It was observed that, in the groups from G-0 to G-3, the maximal
      life-span postinoculation (PI) were 21, 21, 20 and 10 days, the average life
      spans PI were 7.78, 7.98, 7.05 and 3.55 days, and the survival time at 50%
      mortality PI were 6.72, 6.80, 6.40 and 4.00 days, respectively. Daily survival
      rates in the groups G-0, G-1 and G-2 declined slowly, over 25% on the 10th day
      PI, whereas the one in the group G-3 dropped down quickly, to zero on the same
      day. Linear regression analysis on the daily survival rates against the days PI
      showed significant differences between the groups G-0 and G-3 (0.02 > p > 0.01),
      but no significant differences between the groups G-0 and G-1, or between G-0 and
      G-2 (p > 0.5).

PMID- 9031419
TI  - Toxicity of insecticides to Toxorhynchites splendens and three vector mosquitos
      and their sublethal effect on biocontrol potential of the predator.
AB  - Toxicity of six larvicides ie fenthion, temephos, malathion, deltamethrin,
      alphamethrin (Fendona), OMS 3031 and five adulticides ie malathion, fenitrothion,
      propoxur, deltamethrin, permethrin to Aedes aegypti, Culex quiquefasciatus,
      Anopheles stephensi and the predator, Toxorhynchites splendens was studied for
      evaluating safety margin. Concentrations of alphamethrin that killed 50% larvae
      of T. splendens were 53 and 12 times more than that which killed Cx.
      quinquefasciatus and Ae. aegypti. In case of deltamethrin, concentrations
      required to kill 50% larvae of T. splendens were 14 and 5 times more than that
      required against other two species. Other larvicides tested were equally toxic to
      both T. splendens and vector mosquitos. There was no significant difference in
      the toxicity of larvicides to T. splendens and An. stephensi. Deltamethrin was 25
      132 times less toxic to adults of T. splendens in comparison to vector mosquitos.
      For other adulticides the range was 1-10. Immature developmental time of T.
      splendens was not affected by any of the insecticides tested. However, predation
      rate was lowered when larvae of Ae. aegypti previously exposed to fenthion and
      temephos were offered. Whereas, alphamethrin and OMS 3031 did not affect the
      feeding rate of the predator. There was a significant reduction in the pupal
      weight and pupation as a result of the predator feeding on the insecticide
      treated prey. There was a significant negative relationship between rate of
      pupation and dosage. The present study indicates that synthetic pyrethroids owing
      to their higher safety margin can be used in an integrated vector management
      program.

PMID- 9031420
TI  - Dengue vector mosquitos at a tourist attraction, Ko Samui, in 1995.
AB  - On Ko Samui, Thailand there were two epidemics of dengue hemorrhagic fever (DHF)
      in 1966 and 1967, followed by endemics up to 1994. Aedes aegypti and Aedes
      albopictus were the vectors. From January to July 1995, 51 cases of DHF were
      reported, out of these were many foreigners who still suffer from dengue fever
      and return home with negative impression. We carried out an entomological survey
      around the island and collected the mosquitos to detect dengue virus by
      digoxigenin-cDNA probe. The data revealed that Aedes aegypti and Aedes albopictus
      still were abundant and some were infected with dengue virus. Visual larval
      survey indices (HI, CI and BI) were 90.4, 61.3 and 301.3 respectively. Biting
      rate (BR) of Aedes mosquitos was high, the average indoor and outdoor BR were 9.7
      and 100.8 mosquitos/man-hour. From 13 pools of mosquitos, 8 strains of dengue
      virus were detected (61.5%). The results may encourage the local authorities to
      improve vector surveillance and control before the famous island becomes an
      unpleasant island.

PMID- 9031421
TI  - The spectrum of beta-thalassemia mutations in Malays in Singapore and Kelantan.
AB  - The spectrum of beta-thalassemia mutations in Malays in Singapore and Kelantan
      (Northeast Malaysia) was studied. Allele specific priming was used to determine
      the mutations in beta-carriers at -28, Codon 17, IVSI #1, IVSI #5, Codon 41-42
      and IVSII #654 along the beta-globin gene. The most common structural hemoglobin
      variant in Southeast Asia, Hb E, was detected by DNA amplification with
      restriction enzyme (Mnl1) analysis. Direct genomic sequencing was carried out to
      detect the beta-mutations uncharacterized by allele-specific priming. The most
      prevalent beta-mutations in Singaporean Malays were IVSI #5 (45.83%) followed by
      Hb E (20.83%), codon 15 (12.5%) and IVSI #1 and IVSII #654 at 4.17% each. In
      contrast, the distribution of the beta-mutations in Kelantan Malays differed,
      with Hb E as the most common mutation (39.29%) followed by IVSI #5 (17.86%),
      codon 41-42 (14.29%), codon 19 (10.71%) and codon 17 (3.57%). The beta-mutations
      in Kelantan Malays follow closely the distribution of beta-mutations in Thais and
      Malays of Southern Thailand and Malays of West Malaysia. The AAC-->AGC base
      substitution in codon 19 has been detected only in these populations. The
      spectrum of beta-mutations in the Singaporean Malays is more similar to those
      reported in Indonesia with the beta-mutation at codon 15 (TGG-->TAG) present in
      both populations. The characterization of beta-mutations in Singaporean and
      Kelantan Malays will facilitate the establishment of effective prenatal diagnosis
      programs for beta-thalassemia major in this ethnic group.

PMID- 9031422
TI  - Analysis of HLA-DRB1 alleles using PCR-RFLP and PCR-MPH.
AB  - In this study we compare the results of HLA-DRB1 genotyping by PCR-RFLP and PCR
      MPH. HLA-DR specificities were also performed by LCT. Samples were obtained from
      20 Thai patients who were on the waiting list for kidney transplant. DNA was
      extracted by phenol-chloroform extraction. It was found that the results gave
      complete agreement with two methods of DNA typing, however, there were 3
      discrepancies in assigning serologic DR specificities and DNA subtypes (p =
      0.0001) which were due to the cross reactive antibodies and the lack of potent
      antisera to define proper HLA-DR subtypes by LCT. These PCR techniques can be
      applied to identify other alleles such as HLA-DPB1 and HLA-DQB1 which will
      improve the standard histocompatibility testing in the future.

PMID- 9031423
TI  - Increased risk of urinary stone disease by physical exercise.
AB  - Constituents of 6-hour (0900-1500 hours) urine collected during rest and exercise
      have been compared among 3 groups of male volunteers. Groups 1 and 2 (GI, GII)
      were normal controls residing in an urban area (n = 10) and rural villages (n =
      9), respectively, and group 3 (GIII) consisted of 10 renal stone formers from the
      same location as GII. Exercise was performed by cycling on an electronic bicycle
      with three 150-watt loads and the duration of each load was 20 minutes. Collected
      usine was analyzed for volume, pH, PI (permissible increment) in oxalate,
      creatinine, calcium, sodium, potassium, phosphorus, oxalate, uric acid and
      citrate. The results showed that most urinary excretions during both rest and
      exercise periods were similar among the 3 groups. Only the following values were
      significantly different, ie in the rest period, calcium of GIII < GII (p < .01)
      and potassium of GII < GI (p < .05); in the exercise period, potassium of GIII <
      GI (p < .02) and phosphorus of GIII < GII (p < .03). In comparison between the
      rest and exercise periods within each group, the decreased total excretions
      during exercise were creatinine of GI (p < .05) and GIII (p < .05), calcium of
      GII (p < .05) and phosphorus of GIII (p < .05); only calcium of GIII (p < .05)
      was increased. However, when the concentration of each constituent was taken into
      consideration, most constituents increased in concentration during the exercise
      period due to the fall in urinary volume. Furthermore, during exercise both pH
      and PI in oxalate of urine decreased significantly. Thus the results of our study
      suggested that though most total urinary excretion patterns were similar between
      the rest and exercise periods, the risk of stone formation in the urinary tract
      during exercise could be enhanced. The enhanced risk is likely due to 3 main
      factors, ie (1) decrease in urinary volume, (2) increased propensity for
      crystallization of calcium oxalate (PI in oxalate decreased) and (3) decrease in
      urinary pH which will directly cause an increase in saturation level of uric
      acid. This increased risk of stone formation was consistently observed in all
      three groups of subjects.

PMID- 9031424
TI  - The lipoprotein profile of young adults with cerebral atherosclerosis.
AB  - In order to elucidate the relationship between the lipoprotein profile and large
      cerebral artery atherosclerosis in the young adults living in developing Asian
      countries, the serum lipoprotein profile and the luminal diameter of large
      cerebral arteries (internal carotid, middle/anterior cerebral and vertebrobasilar
      arteries) were measured and correlated in 67 young Taiwanese with non-embolic
      cerebral infarct (CI). Totally 23 (21.9%) patients had atherosclerotic stenosis.
      A significant elevation of the serum total cholesterol (TC), triglyceride, total
      lipids, beta-lipoprotein (beta-LP) and pre-beta-LP level was found in
      atherosclerotic CI patients. But multiple regression analysis showed only the
      serum beta-LP (p = 0.0041) and TC (p = 0.0324) level to be the independent risk
      factors for atherosclerosis. Secondary dyslipoproteinemia is the main cause for
      hyperlipoproteinemia in our atherosclerotic patients. Therefore, an abnormal
      lipoprotein profile is linked to large cerebral artery atherosclerosis in young
      Asians regardless of ethnic group. A tailored program is recommended to modify
      the life style and dietary habit, as well as to gain access to secondary control
      for large cerebral atherosclerosis prevention in developing countries.

PMID- 9031425
TI  - The value of positive nitrites in screening asymptomatic bacteriuria amongst
      Malaysian school children.
AB  - It is important to diagnose and treat urinary tract infection in children before
      renal damage has taken place. Hence a new screening procedure will be of
      interest. This study was conducted to evaluate the efficacy of urinary nitrite in
      screening for asymptomatic bacteriuria among school children compared to a more
      traditional method. Of the 44,816 school children investigated 240 (0.54%)
      students were judged to have bacteriuria ie 82 (0.19%) in boys and 158 (0.35%) in
      girls. Escherichia coli was the commonest organism isolated (28.75%). Urine
      dipstick testing for nitrite was found to have a low sensitivity and positive
      predictive value. While urinalysis for pyuria was noted to have a sensitivity of
      77.9%, a specificity of 95.8% and a negative predictive value of 99.9%.

PMID- 9031426
TI  - Food-borne nitrates and nitrites as a cause of methemoglobinemia.
AB  - Methemoglobinemia is a potentially fatal condition. Previous reports of toxic
      methemoglobinemia due to food-borne nitrates and nitrites are reviewed.
      Contamination of food during manufacture or degradation of nitrates in vegetables
      appear to be the most important factors. Some food items, such as refrigerated
      "dim-sum", stuffed pork and Chinese sausages, are very popular among some Asian
      populations; a stringent control against the excessive use of nitrates and
      nitrites is required in order to prevent outbreaks of toxic methemoglobinemia.
      Patients with glucose-6-phosphate dehydrogenase deficiency, a common condition in
      some Asian populations, may present with methemoglobinemia and intravascular
      hemolysis following exposure to oxidant drugs or chemicals. Methylene blue is
      inefficient and may exacerbate hemolysis in these patients; partial exchange
      transfusion may be required.

PMID- 9031427
TI  - Prevalence of lower genital tract infections among Vietnamese women attending a
      maternal and child health center in Hanoi, Vietnam.

PMID- 9031428
TI  - Salmonella as a cause of bacteremia and subdural empyema in a patient with HIV
      infection.

PMID- 9031429
TI  - Infection of an adult in Mie Prefecture, Japan by Bertiella studeri.
AB  - Two gravid strobila without scolex were passed by a 23-year-old male in Mie
      Prefecture, Japan. Morphological features were comparable to characteristics of
      Bertiella studeri. Although two children's cases have already been reported, this
      is the first case of an adult in Japan since the occurrence of B. studeri was
      proven in Japan.

PMID- 9031430
TI  - Acute viral hepatitis A patient with early negative HAV-IGM antibody.
AB  - An acute hepatitis A patient with negative HAV-IgM antibody on presentation is
      reported. The antibody was measured again 11 days later and became positive. To
      confirm the diagnosis of hepatitis A with negative HAV-IgM antibody at early
      stage, the second antibody test approximately 2 weeks apart should be performed.

PMID- 9031431
TI  - Fatal miliary tuberculosis with hypercalcemia.

PMID- 9031433
TI  - Reconstruction of the head and neck.
AB  - The collaboration of surgeons, radiation oncologists, chemotherapists, dentists,
      oral surgeons, prosthodontists, and speech therapists has led to major advances
      in the management of the difficult cancers of the head and neck area. The advent
      of myocutaneous flaps and the facilitation of microsurgical free flaps have
      ushered in an era of one-stage reconstructions to shorten the hospital stay and
      improve the overall therapeutic, functional, and cosmetic results.

PMID- 9031434
TI  - Reconstruction of the orbit.
AB  - There are numerous methods for reconstruction of the orbit. The choices depend on
      the patient's age, the type of tumor, and the specific anatomic and functional
      demands required. Three-dimensional reconstructions, including bone and soft
      tissue, and the particular needs of the ocular system must be considered,
      especially when subtotal or globe preservation procedures are used.

PMID- 9031435
TI  - Reconstruction of the breast.
AB  - The options for breast reconstruction include implant and expander, latissimus
      dorsi flap, TRAM flap, and free flaps. The moratorium on silicone gel implants
      has increased the use of TRAM and free flap breast reconstruction. Immediate
      reconstruction after preoperative planning with the surgical oncologist has
      improved the aesthetic results. Morbidity has been reduced through refinement in
      surgical technique and careful patient selection.

PMID- 9031437
TI  - Reconstruction of the abdomen and perineum in cancer surgery.
AB  - Trunk and perineal defects after tumor resection present a challenge to the
      reconstructive surgeon. When primary closure is not possible, the use of well
      vascularized autogenous tissue is required to achieve adequate soft-tissue
      coverage. Pedicled muscle or myocutaneous flaps provide excellent sources of
      vascularized tissue for postradiation defects. When local tissues preclude the
      use of pedicled flaps, free-tissue transfers can be performed. A thorough
      understanding of radiation wounds and the reconstructive options is essential for
      treatment of these challenging defects.

PMID- 9031436
TI  - Chest wall reconstruction.
AB  - Chest wall resection and reconstruction continue to provide a formidable
      challenge. Prolonged hospitalization of 2 to 3 weeks in often necessary, and
      patients at our institution have undergone an average of two operations to
      achieve final closure. However, in multiple reviews of the senior author's
      personal experience, 85% of patients alive 30 days after operation had a healed,
      asymptomatic chest wall. Most late deaths occur as a result of the underlying
      disease process, usually malignancy.

PMID- 9031438
TI  - Reconstruction of the lower extremity after ablative resection for cancer.
AB  - Limb-sparing surgery for cancer of the lower extremity has ushered the
      development of composite, one-stage reconstructions that employ a combination of
      autologous tissues, bone allografts, and endoprosthetic devices. The success of
      these efforts in preserving limb function has been generally good, yet the
      ultimate level of function is less than normal. Microsurgery has assumed a
      progressively greater role in the reconstruction of composite defects and allows
      much latitude in the surgical planning and in the management of delayed
      complications. Although patients who opt for limb salvage reconstructions
      frequently require more operative procedures and have longer hospitalizations
      than patients undergoing primary amputation, their functional outcome surpasses
      that of the amputation group and thus justifies the surgical effort.

PMID- 9031439
TI  - Reconstruction of the perineum after tumor surgery.
AB  - Major defects of the perineum are often complicated by contracture, radiation
      injuries, fistulas, and infection. In addition, the perineal surface is unique,
      and any replacement must meet the requirements of mobility, sensitivity,
      durability, elasticity, and weight bearing. This combination of complex defects
      and special surface requirements can be met by adequate extirpative procedures
      and reconstruction with a number of muscle, musculocutaneous, and fasciocutaneous
      flap options.

PMID- 9031440
TI  - Plasminogen activation by invasive human pathogens.
AB  - In this review the interaction between invasive human pathogens expressing
      plasmin(ogen) receptors and/or producing plasminogen activators with the human
      plasmin(ogen) system is described. Evidence is presented for multiple mechanisms
      by which human pathogens can acquire a surface bound form of plasmin that cannot
      be regulated by host serpins. The potential importance of these pathways in
      providing the organisms with the ability to cross tissue barriers is discussed.

PMID- 9031441
TI  - Autoantibodies against the protease inhibitor calpastatin: a new risk factor for
      venous thrombosis?
AB  - Autoantibodies reactive against human calpastatin were detected by screening a
      cDNA expression library with the serum of a 53 year old white female patient with
      a history of venous thrombosis and suspected antiphospholipid syndrome. When
      further sera were analyzed it could be shown that > 90% of calpastatin
      autoantibodies, detected by Western blotting against the partial calpastatin
      clone, react with the C-terminal amino acids of the protein. Therefore, an ELISA
      based on a synthetic peptide containing the C-terminal 27 amino acids of
      calpastatin was developed and 205 healthy blood donors and 138 random sera from
      hospital patients were analyzed. A total of 11 sera (3.2%) were positive with no
      significant difference between the two groups (7/205 and 4/138). In 80
      consecutive patients with a history of venous thrombosis 9 positive sera (11.3%;
      p < 0.01 vs. blood donors, p < 0.02 vs. hospital patients) were detected. Our
      results indicate that autoantibodies against calpastatin may constitute a so far
      unknown risk factor for venous thrombosis.

PMID- 9031442
TI  - Two distinct novel splice site mutations in a compound heterozygous patient with
      protein S deficiency.
AB  - Genetic analysis revealed two distinct novel splice site mutations in a compound
      heterozygous patient with protein S deficiency. The paternal mutation was a G-to
      T transition at position-1 of the acceptor splice site of intron N (Mutation I),
      and the maternal mutation was a G-to-C transversion at position-1 of the donor
      splice site of intron C (Mutation II). Both splice site mutations decreased the
      mutated mRNA accumulation to the same extent, approximately 40% of the normal
      mRNA. However, the mutations were associated with different phenotypical
      expressions: the paternal mutant protein S was not detected in vivo, while the
      maternal mutant protein S was present in the plasma in reduced quantity. Because
      Mutation I caused a cryptic splicing in the mutated mRNA, resulting in a reading
      frameshift and premature termination, the predicted mutant protein S might be
      highly unstable. In contrast. Mutation II led to the substitution of Va146 by
      Leu, which might be much less deleterious for the synthesis, secretion and
      stability of the predicted mutant protein S. It was supposed that the different
      post-translational metabolisms produced the distinct phenotypical expressions of
      the mutations.

PMID- 9031443
TI  - Identification of three novel mutations in hereditary protein S deficiency.
AB  - We report the application of single-stranded conformation polymorphism (SSCP)
      analysis to the screening of 15 functionally important Protein S (PS) gene (PS
      alpha) regions (4.243 Kb) in 6 unrelated families with PS deficiencies. Direct
      sequencing of the fragments with altered migration patterns led to the
      identification of the corresponding molecular alterations. A missense mutation, G
      to T transversion at codon Cys598, and two different alterations, leading either
      to allelic exclusion, or premature termination of the protein translation: a G to
      A transition at codon Trp465 and a 1 nt (T) insertion at codon 265, were
      identified. The 1 nt insertion was observed in three apparently unrelated
      families but with a common geographical origin and the mutated allele was
      undetectable in platelet mRNAs of affected individuals. Family analysis
      confirmed, in each case, a perfect cosegregation of the mutation with the PS
      deficiency. We conclude that these alterations represent the causative mutations.

PMID- 9031444
TI  - Prolonged thromboprophylaxis following hip replacement surgery--results of a
      double-blind, prospective, randomised, placebo-controlled study with dalteparin
      (Fragmin)
AB  - Discontinuation of thromboprophylaxis a few days after surgery may unmask delayed
      hypercoagulability and contribute to late formation of deep venous thrombosis
      (DVT). To investigate whether thromboprophylaxis should be prolonged beyond the
      hospital stay, a prospective, double-blind randomised study was conducted in 308
      patients. All patients received initial thromboprophylaxis with dalteparin,
      dextran and graded elastic stockings. On day 7, patients were randomised to
      receive dalteparin (Fragmin) 5000 i.u. once daily, or placebo, for 4 weeks. All
      patients were subjected to bilateral venography, perfusion ventilation
      scintigraphy and chest X-ray on days 7 and 35. Patients with venographically
      verified proximal DVT on day 7 were withdrawn from the randomised study to
      receive anticoagulant treatment. The overall prevalence of DVT on day 7 was
      15.9%. On day 35, the prevalence of DVT was 31.7% in placebo-treated patients
      compared with 19.3% in dalteparin-treated patients (p = 0.034). The incidence of
      DVT from day 7 to day 35 was 25.8% in the placebo-treated group versus 11.8% in
      the dalteparin-treated group (p = 0.017). The incidence of symptomatic pulmonary
      embolism (PE) from day 7 to day 35 was 2.8% in the placebo-treated group compared
      with zero in the dalteparin-treated group. This included one patient who died
      from PE. No patients experienced serious complications related to the injections
      of dalteparin or placebo. This study shows that prolonged thromboprophylaxis with
      dalteparin. 5000 IU, once daily for 35 days significantly reduces the frequency
      of DVT and should be recommended for 5 weeks after hip replacement surgery.

PMID- 9031445
TI  - Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared
      to warfarin for the prevention of venous thromboembolism after total knee
      replacement surgery: a double-blind, dose-ranging study. Ardeparin Arthroplasty
      Study Group.
AB  - We performed a double-blind, randomized clinical trial to compare the efficacy
      and safety of three different subcutaneous (s.c.) low molecular weight heparin
      doses (ardeparin sodium 25, 35, or 50 anti-Xa U/kg twice daily [BID]) to adjusted
      dose warfarin (international normalized ratio [INR] = 2.0 to 3.0), as venous
      thromboembolism prophylaxis after total knee replacement surgery. The primary
      endpoint was total venous thromboembolism prevalence, defined as deep vein
      thrombosis discovered at postoperative venography of the operated leg, or
      symptomatic, objectively-documented pulmonary embolism. Of 860 patients
      randomized, 680 (79%) had an evaluable venogram or pulmonary embolism. The total
      venous thromboembolism prevalence was significantly greater among patients
      prophylaxed with warfarin compared to ardeparin 50 BID (38% vs 27%, p = 0.019);
      the prevalence among ardeparin 25 BID (37%) and 35 BID (28%) patients was similar
      to warfarin and ardeparin 50 BID patients, respectively. Overt bleeding occurred
      in 22 (7.9%) ardeparin 50 BID patients compared to 12 (4.4%) warfarin patients (p
      = 0.08), and in seven ardeparin 25 and 35 BID patients each (5.2% and 5.0%,
      respectively). Compared to the warfarin group, blood loss was significantly
      greater in the ardeparin 50 and 25 BID groups, and not different in the ardeparin
      35 BID group. CONCLUSIONS: Postoperative, unmonitored, fixed-dose ardeparin 50
      anti-Xa U/kg s.c. BID is significantly more effective than adjusted-dose warfarin
      for this indication. Although overt bleeding among warfarin and ardeparin 50 BID
      patients did not differ significantly, ardeparin 50 BID patients had
      significantly greater blood loss. Ardeparin 35 anti-Xa U/kg s.c.BID may provide
      efficacy similar to ardeparin 50 anti-Xa U/kg s.c. BID but with reduced bleeding.

PMID- 9031446
TI  - Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk
      pregnancies.
AB  - Venous thromboembolic disease remains the commonest cause of maternal death. The
      management of thromboprophylaxis in high risk women during pregnancy is
      contentious. Low molecular weight heparins (LMW) have theoretical advantages
      compared with unfractionated heparin and warfarin but have been poorly studied in
      pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in
      thirty four high risk pregnancies. All the women had a previous thrombosis or a
      thrombosis in their current pregnancy +/- a recognised thrombophilic state
      (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to
      maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels
      of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women
      required 5,000U Fragmin once daily during the first trimester unless they were
      greater than 100 kg at the start of pregnancy. The mean time for dosage increase
      was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at
      the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose
      or inserting the needle 6 hours after the previous Fragmin injection. There were
      no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman
      had osteoporotic vertebral collapse post partum, she had no other risk factors
      for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing
      recurrent thromboembolic disease in pregnant women at high risk, but it is
      notable that osteoporotic fractures occurred post partum in one woman. Further
      trials are required to determine optimal dosage and safety.

PMID- 9031448
TI  - Thrombin activity associated with indwelling central venous catheters.
AB  - Thrombotic complications are frequent with indwelling central venous catheters
      and result in catheter dysfunction, vascular obstruction and may also contribute
      to catheter-associated infections. The pathogenesis of catheter thrombosis is not
      well characterized but may involve vessel damage, local stasis and catheter
      associated thrombin formation. We have, therefore, measured the thrombin activity
      associated with central venous catheters removed from patients and have also
      determined the ability of hirudin to inactivate catheter-associated thrombin. We
      obtained 48 catheters from 46 patients and removed 1 cm portions for study. These
      were taken from the distal end, 5 cm proximal, and 15 cm proximal from the end.
      Following washing, thrombin activity was measured with a chromogenic assay.
      Thrombin was associated with 40 of 48 catheters and with 100 of 144 segments with
      a mean activity of 132 +/- 27 microU/cm with a range of 0 to 2,160 microU/cm.
      Incubation in hirudin reduced the activity from a mean of 122 +/- 33 microU/cm to
      18 +/- 6 microU/cm (p < .001). Scanning electron microscopy of selected catheters
      showed that some had areas of fibrin deposition which was not apparent visually.
      The findings indicate that indwelling central venous catheters frequently have
      associated thrombin activity which can be inhibited by a direct-acting thrombin
      inhibitor such as birudin.

PMID- 9031447
TI  - Ongoing prothrombotic state in the portal circulation of cirrhotic patients.
AB  - Portal thrombosis may complicate the clinical course of cirrhosis, but the
      pathophysiologic mechanism is unclear. Aim of the study was to evaluate the
      behavior of clotting system and endotoxemia in portal vein and in peripheral
      circulation of 11 cirrhotic patients undergoing transjugular port-systemic shunt
      (TIPS). Portal blood showed higher values of F1 + 2 [Median (range): 2.5 (1.1
      5.3) vs. 1.1 (0.6-2.1) nM, p < 0.01], D-dimer [765 (184-1713) vs. 192 (64-813)
      ng/ml, p < 0.01] and endotoxemia [31 (16-47.2) vs. 13.7 (7.5-23.5) pg/ml, p <
      0.01] than peripheral circulation. In the portal vein, all but one sample had F1
      + 2 > 1.2 nM (upper limit of control values), all but one had D-dimer > 216 mg/dl
      (mean + 2 SD of controls) and 100% had values of endotoxemia > 9.6 pg/ml (upper
      limit of control values). Fibrinogen was lower in the portal circulation compared
      to peripheral circulation but the difference was not significant [85 (58-195) vs.
      134 (75-244) mg/dl, p > 0.05]. Endotoxemia was directly correlated with F1 + 2
      (Rho = 0.92 p < 0.006) and D-dimer (Rho = 0.93, p < 0.005). This study shows that
      an ongoing prothrombotic state is present in the portal circulation of cirrhotic
      patients and may play a pivotal role in the thrombotic episodes occurring in this
      clinical setting.

PMID- 9031449
TI  - Fibrinolytic and coagulant responses to regional limb perfusions of tumor
      necrosis factor, interferon-gamma, and/or melphalan.
AB  - Regional limb perfusion with antineoplastic agents stresses the local vasculature
      in a variety of ways. However, by monitoring the perfusates from limbs treated
      with melphalan alone or with melphalan plus tumor necrosis factor (TNF) and
      interferon-gamma (IFN-gamma), we were able to distinguish the effect of the
      cytokines on the observed coagulant and fibrinolytic responses. We collected
      samples of effluent from a series of lower extremities that were perfused with
      the cytokines and/or melphalan as treatment for localized melanoma. Both regimens
      produced statistically significant evidence of coagulant and fibrinolytic
      activation. However, limbs receiving cytokines in addition to the melphalan
      responded with a sharper rise in tissue plasminogen activator (tPA) and plasmin
      (plasmin-antiplasmin complexes [PAP]) than limbs treated with melphalan alone.
      Evidence of thrombin formation (prothrombin fragment 1 + 2 [F1 + 2], thrombin
      antithrombin complexes [TAT]) was also greater when the cytokines were included,
      although the response was delayed and less consistent than the fibrinolytic
      activation.

PMID- 9031451
TI  - Tissue factor (TF) and urokinase plasminogen activator receptor (uPAR) and
      bleeding complications in leukemic patients.
AB  - Tissue factor (TF) and urokinase receptor (uPAR) are key cellular receptors
      triggering, respectively, coagulation and fibrinolysis. Bleeding complications
      among leukemic patients have been related to an abnormal expression of TF by
      blast cells and/or to an abnormal fibrinolytic response. In this study the
      expression of TF and uPAR has been assessed in 18 acute non-lymphoblastic and 8
      lymphoblastic leukemic blast cells using several methodological approaches. TF
      mRNA was evaluated by in situ hybridization and TF and uPAR antigen were
      evaluated immunologically in cell lysates and on the cell surface by flow
      cytometry. In addition, TF-procoagulant activity was measured in coagulation
      based assays. The reliability of these methods was corroborated in six leukemic
      cell lines of different lineages and states of maturation. Disseminated
      intravascular coagulation was detected in two M3 leukemia patients whose blast
      cells expressed high amounts of TF. Hyperfibrinolysis was detected in one M1 and
      two M2 patients, whose blast cells displayed a high content of uPAR antigen, but
      no TF. Furthermore, M5 leukemia blast cells expressed both TF and uPAR, although
      no hemostatic defects or bleeding complications were detected in these patients.
      Taken together, although a limited number of patients was included in this study,
      these data suggest that in leukemia patients exhibiting bleeding, either TF or
      uPAR are expressed by their blast cells. However, the presence of these receptors
      does not necessarily imply the existence of a hemostatic disorder.

PMID- 9031450
TI  - Systemic thrombin generation and activity resistant to low molecular weight
      heparin administered prior to streptokinase in patients with acute myocardial
      infarction.
AB  - One hundred patients were included in a randomized open trial to assess the
      systemic factor Xa (FXa) and thrombin inhibitory effect as well as the safety
      profile of low molecular weight heparin (LMWH) given subcutaneously in
      conjunction with streptokinase (SK) in patients with acute myocardial infarction
      (MI). The treatment was initiated prior to SK, followed by repeated injections
      every 12 h for 7 days, using a dose of 150 anti-Xa units per kg body weight. The
      control group received unfractionated heparin (UFH) 12,500 i.u. subcutaneously
      every 12 h for 7 days, initiated 4 h after start of SK infusion. All patients
      received acetylsalicylic acid (ASA) initiated prior to SK. Serial blood samples
      were collected prior to and during the first 24 h after initiation of SK infusion
      for determination of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin
      III (TAT) complexes, fibrinopeptide A (FPA) and cardiac enzymes. Bleeding
      complications and adverse events were carefully accounted for. Infarct
      characteristics, as judged by creatine kinase MB isoenzyme (CK-MB) and cardiac
      troponin T (cTnT), were similar in both groups of patients. A comparable
      transient increase in F1 + 2, TAT and FPA was noted irrespective of heparin
      regimen. Increased anti-Xa activity in patients given LMWH prior to thrombolytic
      treatment had no impact on indices of systemic thrombin activation. The incidence
      of major bleedings was significantly higher in patients receiving LMWH as
      compared to patients receiving UFH. However, the occurrence of bleedings was
      modified after reduction of the initial LMWH dose to 100 anti-Xa units per kg
      body weight. In conclusion, systemic FXa- and thrombin activity following SK
      infusion in patients with acute MI was uninfluenced by conjunctive LMWH
      treatment.

PMID- 9031452
TI  - Enhanced response to chemotactic activation of polymorphonuclear leukocytes from
      patients with heart valve replacement.
AB  - Artificial surfaces activate blood components. Since anticoagulant and
      antiplatelet therapy fail to abolish thromboembolic complications in patients
      with mechanical heart valve replacement (MHVR), other mechanisms might contribute
      to switch on a thrombotic event. We therefore investigated the reactivity to
      chemotactic activation of PMN from patients with MHVR. PMN responses were
      analyzed in 3 groups: 130 patients with MHVR and oral anticoagulant therapy, with
      or without aspirin, 57 patients on a comparable antithrombotic regimen, but
      without MHVR and 50 healthy subjects. In vitro studies showed that the release of
      cathepsin G and elastase from fMLP-stimulated PMN was significantly higher in the
      MHVR group, the leukocyte content of alpha 1-antitrypsin (an inhibitor of both
      enzymes) being similar in all three groups. CD11b expression after stimulation
      with fMLP was also significantly higher on PMN from MHVR patients than from
      control patients or healthy volunteers, while PMN CD11b basal expression was
      similar in all three groups. This increased PMN response in vitro in the absence
      of an obvious activation in vivo, may reflect a modified reactivity of
      circulating PMN passing through the artificial valves. Increased reactivity to
      local stimuli might allow PMN to participate in thrombus formation, despite
      conventional antithrombotic therapy.

PMID- 9031453
TI  - Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary
      hyperlipidaemia.
AB  - An elevated plasma fibrinogen level is increasingly accepted as an independent
      risk indicator of cardiovascular disease. This has enhanced the interest in
      identifying agents that can normalize elevated plasma fibrinogen levels. One
      group of agents with this capacity are the fibric acid derivatives, e.g.
      ciprofibrate and gemfibrozil. We studied fibrinogen levels after 12 weeks of
      treatment with ciprofibrate (n = 48) and gemfibrozil (n = 51) in
      hypercholesterolenic patients. The correlation of the decrease in fibrinogen with
      lipid lowering and the contribution of the acute phase and genetic polymorphisms
      to this decrease were also evaluated. After 12 weeks of treatment, the fibrinogen
      levels were significantly decreased (p < 0.0005) with both drugs, although the
      decrease in the ciprofibrate group (mean 3.4 g/l pre-treatment to 2.4 g/l after
      12 weeks) was larger than in the gemfibrozil group (mean 3.4 g/l to 3.0 g/l). The
      lipid lowering effect was comparable for the two drugs but there was no
      correlation for either ciprofibrate or gemfibrozil between the lipid lowering and
      the magnitude or the velocity of the fibrinogen lowering effect. An attenuation
      of the major regulatory mechanism of plasma fibrinogen levels, the acute phase
      reaction, was invoked as the underlying mechanism. However, pre-treatment C
      reactive protein levels were not increased and did not change after treatment.
      Moreover, no effects of the polymorphisms of the fibrinogen beta-gene on the
      decrease of the plasma fibrinogen levels were observed. This suggests that a new,
      as yet unknown, mechanism is involved in fibrinogen lowering by fibrates.

PMID- 9031454
TI  - Factor VIII inhibitors in previously treated haemophilia A patients with a double
      virus-inactivated plasma derived factor VIII concentrate.
AB  - Antibodies to factor VIII (inhibitors) are usually produced at the beginning of
      treatment with factor VIII and are rare in multitransfused patients. Such
      antibodies are deemed to be patient-related, as supported by the description of a
      number of associated risk factors. However, a second category of inhibitors has
      recently been identified, namely antibodies occurring in multitransfused patients
      as a result of exposure to a particular factor VIII concentrate. A first outbreak
      of product-related inhibitors was recently described. The present paper describes
      the second well-documented occurrence of such inhibitors. Eight out of 140
      multitransfused patients with severe haemophilia A developed an inhibitor to
      factor VIII shortly after changing treatment to a double-virus inactivated plasma
      derived factor VIII concentrate. In addition to solvent-detergent treatment, this
      concentrate was pasteurised at 63 degrees C for 10 hours. Exposure to the
      pasteurised product before inhibitor detection ranged from 9 to 45 days.
      Inhibitor titers varied between 2.2 and 60 Bethesda Units and recovery of
      transfused factor VIII ranged from 0.21 to 0.68 (expressed as i.u./dl factor VIII
      rise per i.u./kg administered). In contrast to usual inhibitors in haemophilia A
      patients, these product-related inhibitors showed complex inhibition kinetics.
      They were found specific for the factor VIII light chain. The inhibitors
      gradually declined when exposure to the pasteurised product was stopped, despite
      further treatment with other factor VIII concentrates. The present data stress
      the importance of carefully monitored clinical studies, both in previously
      treated and previously untreated patients, before introduction of a new or
      modified clotting factor concentrate.

PMID- 9031455
TI  - Family history of coronary heart disease and hemostatic variables in middle-aged
      adults. Atherosclerosis Risk in Communities Investigators and Family Heart Study
      Research Group.
AB  - Individuals with a family history of coronary heart disease (CHD) may be
      predisposed to atherothrombosis. To investigate this hypothesis, a family CHD
      risk score was computed for approximately 13,000 men and women aged 45 to 64;
      hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand
      factor, antithrombin III. protein C) were also measured in plasma. After
      adjustment for age and ethnicity, there was a statistically significant, positive
      association between the family risk score and four of the six hemostatic
      variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor) in women
      and all six hemostatic variables in men. In general, these associations were weak
      and substantially attenuated after adjustment for constitutional, lifestyle, and
      biochemical covariates. These results indicate that mean levels of selected
      hemostatic variables, like traditional CHD risk factors, are higher in
      individuals with a family history of heart disease.

PMID- 9031457
TI  - Coagulation and fibrinolysis factors in healthy subjects consuming high stearic
      or trans fatty acid diets.
AB  - The effects of stearic acid (C18:0) and trans fatty acids on variables related to
      coagulation and fibrinolysis were studied in 80 healthy humans average age 29 +/-
      9 years. All subjects consumed a baseline diet high in saturated fatty acids,
      mainly from dairy fat for 5 weeks. After this baseline diet they were allocated
      either to a diet high (8.7% of energy, En%) in trans fatty acids from partially
      hydrogenated vegetable oil (40 subjects) or a diet high (9.3 En%) in stearic acid
      (40 subjects) for 5 weeks. All diets contained 32.2-33.9 En% fat, 14.6-15.8 En%
      saturated plus trans fatty acids, 12.2-12.5 En% cis-monounsaturated and 2.9-3.5
      En% polyunsaturated fatty acids and 216-250 mg/10 MJ cholesterol. The fats were
      mixed into solid foods and almost all daily food was provided. In comparison with
      the baseline dairy fat diet no change was observed in the concentrations of
      plasma fibrin degradation products and D-dimers. Also the factor VII coagulant
      activity (F VII:C), tissue type plasminogen activity (tPA) and plasminogen
      activator inhibitor activity (PAI-1) were not affected by the experimental diets.
      Small increase in plasma fibrinogen concentration during the stearic acid diet
      was statistically significant (from 3.49 to 3.63 g/l: p = 0.041), but probably
      without any biological significance. Both diets increased plasma level of
      lipoprotein Lp(a). It can be concluded that as far as coagulation and
      fibrinolysis are concerned there is no need to differentiate between stearic acid
      or trans monoenoic fatty acids.

PMID- 9031456
TI  - Haemostatic variables in Pacific Islanders apparently free from stroke and
      ischaemic heart disease--the Kitava Study.
AB  - We cross-sectionally measured plasminogen activator inhibitor-1 (PAI-1) activity,
      fibrinogen, factor VII (FVII:C) and VIII (FVIII:C) coagulant activity, and von
      Willebrand factor antigen (VWF:Ag) in 162 traditional horticulturalists older
      than 40 years from the tropical island of Kitava, Papua New Guinea, where the
      intake of western food is negligible and where stroke and ischaemic heart disease
      appear to be absent. Identical analyses were made in Swedish subjects of
      comparable ages. Kitavams had markedly lower PAI-1 activity, with 85% of males
      and 100% of females having PAI-1 activity < or = 5 U/ml, as compared with 22 and
      14% in Swedish males and females (p < 0.0001). Surprisingly, Kitavans also had
      higher FVII:C. FVIII:C and VWF:Ag. Fibrinogen was 10% lower in Kitavan males
      while 25% higher in Kitavan females. The very low PAI-1 activity in Kitavans may
      explain some of their apparent freedom from cardiovascular disease and probably
      relates to their extreme leanness.

PMID- 9031458
TI  - The effect of progesterone on the haemostatic mechanism.
AB  - The hemostatic effect of progesterone administered vaginally at a dose of 100 mg
      twice a day throughout one menstrual cycle was investigated and compared with the
      coagulation factors in one untreated normal menstrual cycle in 15 women. The
      progesterone treatment resulted in a 20-fold progesterone rise in the early
      follicular phase from 1.2 nmol/l in the pretreatment control cycle to levels
      between 26 and 29 nmol/l during treatment. Ovulation was completely suppressed in
      seven women while eight women showed a slight rise in progesterone on treatment
      days 20 to 25 not compatible with the rise which could have been expected if
      ovulation had occurred. The effects found on haemostasis during progesterone
      treatment varied with the menstrual cycle and were so small that they could as
      well be due to chance and not to treatment.

PMID- 9031459
TI  - Rapid direct determination of low and high molecular weight kininogen in human
      plasma by Particle Concentration Fluorescence Immunoassay (PCFIA).
AB  - In this study, we employed Particle Concentration Fluorescence Immunoassay
      (PCFIA), for directly measuring both high and low molecular weight kininogens (HK
      and LK) in human plasma. In 38 normal donors, the mean values for plasma
      kininogens were 93 mg/ml +/- 19 SD, 82 mg/ml +/- 12 SD, and 175 mg/ml +/- 29 SD,
      respectively for LK, HK, and TotK (the sum of LK and HK detected by their common
      heavy chains). Plasma completely deficient in HK and LK was unreactive (< 0.25
      mg/ml) in all 3 assays whereas plasma from a patient with Fitzgerald Trait had an
      HK value of 11 mg/ml, an LK value of 36 mg/ml and a TotK value of 59 mg/ml. The
      reagents can be prepared in advance and all three kininogen determinations can be
      performed, using the same diluted sample on 24 plasma samples, in triplicate, or
      40 plasma samples, in duplicate, in less than 1 h. By performing all 3 kininogen
      determinations, it is possible to differentiate cleaved from intact kininogens.
      This technique will facilitate the widespread screening of kininogen levels in
      biological fluids of normal humans as well as of patients with various diseases.

PMID- 9031460
TI  - Genetic diagnosis of factor V Leiden using heteroduplex technology.
AB  - A new genetic test has been developed for detection of the mutation known as
      factor V Leiden. The test employs heteroduplex technology and comprises a single
      PCR reaction followed immediately by PCR product analysis. It therefore
      represents the minimum practical route from blood/tissue sample to genetic
      result. A cohort of 100 patients with a history of thrombosis have been screened
      using both the new heteroduplex test and a previously described PCR-restriction
      endonuclease test. Results gave 100% correlation: normals 75 (75%), heterozygotes
      24 (24%) and homozygotes 1 (1%). The heteroduplex test has been shown to give
      straightforward diagnosis in three different analytical systems: standard
      polyacrylamide gel electrophoresis (PAGE), mini-gel PAGE and capillary
      electrophoresis. The latter system is semiautomated, therefore rapid through-put
      of large sample numbers is now possible.

PMID- 9031461
TI  - Utilization of dilute Russell's viper venom time to detect autoantibodies against
      beta 2-glycoprotein I which express anticoagulant activity in the presence but
      not in the absence of exogenous phospholipids.
AB  - Lupus anticoagulant (LA) is a general term to define immunoglobulins interfering
      with phospholipid-dependent coagulation tests. It is now clear that the
      phospholipid-dependence of some LA is related to the presence of the phospholipid
      binding plasma protein beta 2-glycoprotein I (beta 2-GPI) and that autoantibodies
      to beta 2-GPI might represent a specific category of LA. To verify this
      hypothesis we have purified IgG autoantibodies to beta 2-GPI from plasma of 6
      patients with antiphospholipid antibody syndrome, by means of agarose-immobilized
      human beta 2-GPI. All 6 preparations tested positive in anti-beta 2-GPI IgG
      antibody ELISA and showed a marked LA activity by prolonging dilute Russell Viper
      Venom Time (dRVVT) from a minimum of 5.3 s in patient # 1 to a maximum of 41.1 s
      in patient # 3. These IgG preparations behaved as typical LA, with this activity
      tending to disappear in the presence of increasing phospholipid (PL)
      concentrations. Moreover, the LA activity of the IgG preparations was not
      detectable in the absence of PL, in which case the ratio between dRVVT obtained
      in the presence and absence of IgG autoantibodies to beta 2-GPI was close to 1.
      This pattern was confirmed by using plasma from patients with antiphospholipid
      antibody syndrome testing positive for anti-beta 2-GPI IgG antibodies. These
      findings suggest that dRVVT performed both in the presence and absence of PL
      might constitute a sensitive screening test to detect specific antibodies with LA
      activity.

PMID- 9031462
TI  - Effect of a 15-minute infusion of DDAVP on the pharmacokinetics and
      pharmacodynamics of REVASC during a four-hour intravenous infusion in healthy
      male volunteers.
AB  - Plasma pharmacokinetics, effect on coagulation parameters, and safety and
      tolerability of an intravenous infusion of REVASC before, during and after a
      DDAVP infusion were investigated. Twelve healthy volunteers were given an
      intravenous bolus dose followed by a constant rate four-hour infusion of REVASC.
      Fifteen-minute infusions of 0.9% saline and DDAVP were started two and three
      hours respectively after the start of the REVASC infusion. Plasma REVASC
      concentrations were not affected by either the saline or DDAVP infusion. REVASC
      infusion produced an increase in APTT which plateaued between 0.5 and 3 hours.
      After the DDAVP infusion there was a tendency towards a new lower plateau whilst
      the REVASC infusion continued. There were no serious adverse events or bleeding
      episodes throughout the study. In conclusion, the co-administration of
      intravenous DDAVP has no effect on the plasma pharmacokinetics of REVASC and
      partially reverses the REVASC-induced increase in APTT. This may represent a role
      for DDAVP in the partial reversal of anticoagulation induced by REVASC.

PMID- 9031463
TI  - Pharmacokinetics and tolerability of a new low molecular mass heparin (RO-11) in
      healthy volunteers--a dose-finding study within the therapeutical range.
AB  - This paper reports on the results of a Phase I, dose-finding study with a new low
      molecular mass heparin (LMMH) called RO-11. The study focused on
      pharmacokinetics, dose-effect relationship and on tolerability of three single
      subcutaneous (s.c.) doses within the therapeutical range. After the injection of
      7,500, 9,000 and 12,500 anti-FXa i.u., the anti-FXa effect peaked between 3-6 h
      and showed a dose-dependent response. The absorption and elimination were first
      order processes and the long half-life (> 5 h) kept constant after increasing
      doses. The compound was tolerated very well and no clinically relevant
      prolongation of APTT, prothrombin and thrombin clotting tests was observed. At
      the dose of 7,500 i.u., which corresponded to 110 anti-FXa i.u./Kg, RO-11 exerted
      anti-FXa effect for at least 18-20 h. We recommend using this dose in a single
      s.c. injection, to evaluate the efficacy and safety of RO-11 in the initial
      treatment of DVT or PE.

PMID- 9031464
TI  - Enhancement of plasminogen binding to U937 cells and fibrin by complestatin.
AB  - Plasminogen binds to endothelial and blood cells as well as to fibrin, where the
      zymogen is efficiently activated and protected from inhibition by alpha 2
      antiplasmin. In the present study we have found that complestatin, a peptide-like
      metabolite of a streptomyces, enhances binding of plasminogen to cells and
      fibrin. Complestatin, at concentrations ranging from 1 to 5 microM, doubled 125I
      plasminogen binding to U937 cells both in the absence and presence of
      lipoprotein(a), a putative physiological competitor of plasminogen. The binding
      of 125I-plasminogen in the presence of complestatin was abolished by epsilon
      aminocaproic acid, suggesting that the lysine binding site(s) of the plasminogen
      molecule are involved in the binding. Equilibrium binding analyses indicated that
      complestatin increased the maximum binding of 125I-plasminogen to U937 cells
      without affecting the binding affinity. Complestatin was also effective in
      increasing 125I-plasminogen binding to fibrin, causing 2-fold elevation of the
      binding at approximately 1 microM. Along with the potentiation of plasminogen
      binding, complestatin enhanced plasmin formation, and thereby increased
      fibrinolysis. These results would provide a biochemical basis for a
      pharmacological stimulation of endogenous fibrinolysis through a promotion of
      plasminogen binding to cells and fibrin.

PMID- 9031465
TI  - Lateral mobility of integrin alpha IIb beta 3 (glycoprotein IIb/IIIa) in the
      plasma membrane of a human megakaryocyte.
AB  - The migration of integrins to sites of cell-cell and cell-matrix contact is
      thought to be important for adhesion strengthening. We studied the lateral
      diffusion of integrin alpha IIb beta 3 (glycoprotein IIb/IIIa) in the plasma
      membrane of a cultured human megakaryocyte by fluorescence recovery after
      photobleaching of FITC-labelled monovalent Fab fragments directed against the
      beta 3 subunit. The diffusion of beta 3 on the unstimulated megakaryocyte showed
      a lateral diffusion coefficient (D) of 0.37 x 10(-9) cm2/s and a mobile fraction
      of about 50%. Stimulation with ADP (20 microM) or alpha-thrombin (10 U/ml) at 22
      degrees C induced transient decreases in both parameters reducing D to 0.21 x 10(
      9) cm2/s and the mobile fraction to about 25%. The fall in D was observed within
      1 min after stimulation but the fall in mobile fraction showed a lag phase of 5
      min. The lag phase was absent in the presence of Calpain I inhibitor, where-as
      cytochalasin D completely abolished the decreased in mobile fraction. The data
      are compatible with the concept that cell activation induces anchorage of 50% of
      the mobile alpha IIb beta 3 (25% of the whole population of receptor) to the
      cytoplasmic actin filaments, although, as discussed, other rationals are not
      ruled out.

PMID- 9031466
TI  - Protein tyrosine phosphatase SHP-1 fails to associate with cytoskeleton but is
      normally phosphorylated upon thrombin stimulation of thrombasthenic platelets.
AB  - SHP-1 is a cytoplasmic protein tyrosine phosphatase predominantly expressed in
      hematopoietic cells. Upon thrombin stimulation of human platelets, SHP-1 is
      rapidly phosphorylated on both serine and tyrosine residues, and becomes
      associated with the cytoskeleton, where it could participate in the formation of
      multiprotein signalling complexes. In order to discriminate between signalling
      events occurring downstream of G-protein-coupled thrombin receptor and those
      subsequent to integrin alpha IIb beta 3 engagement, SHP-1 behaviour was examined
      in platelets from two patients lacking integrin alpha IIb beta 3 (Glanzmann's
      thrombasthenia). Upon thrombin stimulation, phosphorylation of SHP-1 occurred
      normally in thrombasthenic platelets, whereas association with the cytoskeleton
      was abolished. Moreover, inhibition of normal platelet aggregation with the
      tetrapeptide arg-gly-asp-ser (RGDS) which impairs fibrinogen binding to integrin
      alpha IIb beta 3, did not alter significantly SHP-1 phosphorylation. It is
      concluded that SHP-1 phosphorylation is not a consequence of integrin signalling
      but might rather occur downstream of thrombin receptor and heterotrimeric G
      proteins.

PMID- 9031468
TI  - Identification of the NO synthase isoforms expressed in human neutrophil
      granulocytes, megakaryocytes and platelets.
AB  - Using Western blot and fluorescent immunocytochemistry, NOS III (or ecNOS) and
      NOS II (or iNOS), but no NOS I (or ncNOS), were identified in preparations of
      human platelets. Reverse-transcription polymerase chain reactions (RT-PCR)
      demonstrated NOS III mRNA, but no NOS II mRNA (which is short-lived) and no NOS I
      mRNA in platelets. Immunofluorescent staining of human bone marrow smears showed
      the presence of NOS III, but not NOS I in megakaryocytes. A subpopulation of
      megakaryocytes also expressed NOS II. In preparations of human neutrophils,
      immunocytochemistry demonstrated NOS I in all cells, whereas no NOS III was
      detected. The few NOS II positive cells were characterized as contaminating
      eosinophils. Similarly, in RT-PCR, transcripts for NOS I and NOS II, but not for
      NOS III, were identified. Thus, the constitutive NOS isoform in megakaryocytes
      and platelets is NOS III, whereas neutrophils express NOS I. Some megakaryocytes
      and eosinophils also express NOS II.

PMID- 9031467
TI  - Isolation and regulation of the cGMP-inhibited cAMP phosphodiesterase in human
      erythroleukemia cells.
AB  - The predominant cAMP phosphodiesterase in human platelets is the low K(m) cGMP
      inhibited phosphodiesterase (PDE 3A). We have isolated native PDE3A from
      platelets and human erythroleukemia (HEL) cells and studied its kinetics. The
      platelet and HEL cell enzymes hydrolyze cAMP with a K(m) = 0.5 microM. Incubation
      of cell supernatant with cAMP dependent protein kinase resulted in a rapid
      increase in activity within minutes, which resulted from a 2-fold decrease in
      K(m) with no increase in Vmax. HEL cells grown for 24 h in the presence of 50
      microM forskolin, an adenylate cyclase activator, demonstrate further increase in
      PDE3A of 274% of control (p = 0.03). Cells incubated with forskolin and
      cycloheximide or actinomycin D demonstrated no increase suggesting that cAMP
      stimulates PDE3A synthesis by transcriptional regulation. The results indicate
      that cAMP affects both the short and long-term regulation of PDE3A. The latter
      effect may play a role in the developing hematopoietic cell and the
      cardiovascular system to regulate cAMP levels.

PMID- 9031469
TI  - PEGylation of interleukin-6 effectively increases its thrombopoietic potency.
AB  - The in vivo thrombopoietic activity of polyethylene glycol-modified interleukin-6
      (MPEG-IL-6), in which 54% of the 14 lysine amino groups of IL-6 were coupled with
      PEG, was compared to that of native IL-6. Native IL-6 and MPEG-IL-6, which showed
      about 51% of the specific bioactivity of native IL-6, were administered
      subcutaneously to mice every 2 days for 7 days. Native IL-6 increased not only
      the peripheral platelet count, but also the plasma-IgG1 level in a dose-dependent
      manner. MPEG-IL-6 showed about 500 times higher thrombopoietic potency than
      native IL-6. Further, in comparison to native IL-6, MPEG-IL-6 did not enhance
      IgG1 production as much as it enhanced platelet production. MPEG-IL-6
      significantly stimulated platelet recovery in mice treated with 5-fluorouracil,
      whereas the administration of native IL-6 had a negligible effect. The plasma
      half-life of MPEG-IL-6 was about 100-fold longer than that of native IL-6. The
      decrease in the plasma clearance of MPEG-IL-6 was thought to be due, in part, to
      the shielding of the proteolytic sites in the IL-6 molecule by the PEG chain. The
      uptake of IL-6 by the reticuloendothelial system, such as the liver and spleen,
      was markedly limited by PEGylation. The PEGylation of IL-6 markedly enhanced the
      blood-residency of IL-6, resulting in effective augmentation of its
      thrombopoietic activity and a marked decrease in its side-effects. These findings
      suggest that MPEG-IL-6 may be a potential candidate for thrombopoietic agent.

PMID- 9031470
TI  - Abnormal proteolytic processing of von Willebrand factor Arg611 Cys and
      Arg611His.
AB  - The structural and functional properties of plasma and platelet vWF were studied
      in 8 patients (5 unrelated families) with vWD demonstrating a mutation at
      position 611 (R611C or R611H). Following reduction, electrophoresis and
      immunoblotting with a polyclonal anti-reduced vWF antibody, abnormal proteolysis
      of vWF was demonstrated in plasma and to a lesser extent in platelets from all
      patients, leading to the formation of a unique 209 kDa fragment undetectable in
      control as well as in type 2A, 2B or 2N vWF. Immunoblotting with MoAbs to reduced
      vWF showed that the C-terminal end of the 209 kDa fragment was located beyond
      residue 1744 of the subunit and that its N-terminus was between residues 523 and
      1114. Multimeric analysis of patients vWF showed an abnormal pattern in both
      plasma and platelets, with a moderate decrease of the HMW multimers together with
      a significant increase of the lowest MW forms. The specific sensitivity of vWF
      R611C and vWF R611H to proteolysis was further evidenced using V-8 protease. In
      all patient's samples the enzyme produced a unique monomeric 80 kDa fragment,
      absent in V-8 digested normal vWF, which overlapped the N-terminal part of the
      subunit. The functional analysis of vWF showed a markedly decreased affinity of
      mutated plasma vWF for platelet GPIb in the presence of ristocetin. Infusion of
      DDAVP in two of these patients did not lead to significant platelet count change.
      It induced a limited increase of the HMW multimers in plasma together with a poor
      correction of the vWF binding to platelet GPIb. In conclusion, our data
      demonstrate that in addition to a normal proteolysis, vWF mutated at position 611
      undergoes a specific cleavage in plasma and platelets. In contrast to the
      increased proteolysis observed in type 2A and 2B patients' plasma, this
      additional cleavage produced a unique 209 kDa species but maintained a HMW
      multimer-like structure of vWF R611C and R611H.

PMID- 9031471
TI  - Two new closely related rat models with relevance to arterial thrombosis-
      efficacies of different antithrombotic drugs.
AB  - Two thrombosis models in rats are described in which mixed type thrombi are
      formed at arterial and venous flow rates. The models, containing a silk thread in
      the aorta and vena cava, respectively, were characterised for the activity of
      three platelet inhibitors, three thrombin active site inhibitors and five
      glycosaminoglycans (GAGs). In the two models a similar highly platelet-dependent
      thrombus developed both in size and composition during the first 10 min after
      insertion of the silk thread. The thrombotic processes were self-limiting, thus
      maintaining blood flow, but persisted twice as long in the vena cava model. In
      both models the thrombus consisted for more than 65% of platelets. Thrombus
      development under arterial as well as under venous flow conditions was inhibited
      dose dependently by all tested compounds including aspirin and the synthetic
      alpha-methyl glycoside copy of the ATIII binding pentasaccharide within heparin,
      Org31540/SR90107A. Simultaneous fibrin deposition and platelet activation, which
      represents an essential element of arterial thrombosis, initially dominated-in
      both models. The gradual thrombus outgrowth, in the cava model, was more
      sensitive to factor Xa selective anti-coagulants, as is venous thrombosis.

PMID- 9031472
TI  - Local delivery of platelets with encapsulated iloprost to balloon injured pig
      carotid arteries: effect on platelet deposition and neointima formation.
AB  - Local delivery of a drug to the arterial wall during angioplasty is an approach
      which might reduce the incidence of occlusive events such as thrombosis and
      restenosis, without the risk of systemic side effects. By exploiting their
      natural primary haemostatic properties, platelets, with encapsulated drugs, can
      be targeted to a vessel wall injury site and act as a depot for sustained
      release. The platelet plasma membrane can be reversibly permeabilised by high
      voltage, short duration electrical pulses (electroporation). Drugs will diffuse
      into porated platelets and become trapped on resealing. We have studied the
      effects of autologous platelets, electroloaded with the stable prostacyclin
      analogue, iloprost on platelet deposition and neointima formation in a pig
      carotid angioplasty model. Iloprost loaded or control platelets were delivered
      locally and immediately to the balloon injured site using a double balloon
      delivery catheter. Acute platelet deposition was measured using 111-Indium, and
      neointima formation at 21 days post angioplasty was assessed by morphometric
      analysis. In pigs treated with iloprost loaded platelets, platelet deposition on
      the artery at 2 hours post injury was dramatically reduced (to approximately
      monolayer coverage), when compared with arteries from pigs treated with control
      platelets. In pigs with deeply injured arteries, i.e. with extensively ruptured
      internal elastic lamina (IEL), platelet deposition was reduced by 88% compared
      with control arteries (118 +/- 20 x 10(6)/cm vs. 14 +/- 2 x 10(6)/cm, means +/-
      SI, 2P < 0.001). In minimally injured arteries (IEL intact) a 65% reduction in
      platelet deposition was observed (55 +/- 24 x 10(6)/cm vs. 19 +/- 3 x 10(6)/cm.
      2P < 0.002). A high concentration of free iloprost, delivered to the angioplasty
      site, with control platelets, had far less effect on platelet deposition,
      substantiating the advantage of platelet encapsulation. At 21 days post injury,
      morphometry of the carotid arteries after treatment with iloprost loaded
      platelets showed significant reductions in intimal area and intimal/medial ratios
      in minimally injured vessels (P < 0.05) as compared with vessels from pigs
      treated with control platelets. With deeply injured vessels, the mean differences
      (control vs. treated) for the same morphometric parameters were not significant.
      This novel approach of electro-encapsulating drugs within autologous platelets,
      and using them as highly biocompatible and biodegradable drug targeting vehicles
      might, with the appropriate choice of encapsulated agent, have potential for
      reducing the incidence of occlusion after angioplasty and thrombolysis
      procedures.

PMID- 9031473
TI  - Antithrombin mutation database: 2nd (1997) update. For the Plasma Coagulation
      Inhibitors Subcommittee of the Scientific and Standardization Committee of the
      International Society on Thrombosis and Haemostasis.

PMID- 9031474
TI  - A 5-nucleotide insertion in the antithrombin gene causing a quantitative
      antithrombin deficiency.

PMID- 9031475
TI  - The 10-base-pair insertion in the promoter of the factor VII gene is not
      associated with lower levels of factor VIIc in Afrocarribeans.

PMID- 9031476
TI  - Prevalence of factor V Leiden in young adults with retinal vein occlusion.

PMID- 9031477
TI  - Prevalence of mutated factor V ARG506 to GLN in Italians.

PMID- 9031478
TI  - Impact of the blood collection tube on the activation of coagulation.

PMID- 9031479
TI  - Clinical significance of platelet size in inflammatory bowel disease?

PMID- 9031481
TI  - A new flow cytometry method of platelet-derived microvesicle quantitation in
      plasma.

PMID- 9031482
TI  - Anticardiolipin antibodies and recurrent thromboembolism.

PMID- 9031483
TI  - Up-regulated tissue factor expression in antiphospholipid syndrome.

PMID- 9031484
TI  - Ticlopidine antagonizes acenocoumarol treatment.

PMID- 9031485
TI  - Looking back in anger: retrospection in the face of a paradigm shift.

PMID- 9031486
TI  - The potential impact of recombinant factor VIII on hemophilia care and the demand
      for blood and blood products.

PMID- 9031487
TI  - The irradiation of blood and blood components to prevent graft-versus-host
      disease: technical issues and guidelines.
AB  - In recent years, there have been several advances in blood irradiation practice.
      These include a better definition of the most appropriate dose level that should
      be used when irradiating blood components. Commercial innovation has provided the
      tools for a quality assurance program to assess the dose that is delivered
      throughout the canister in a free-standing irradiator, and, through the use of
      radiation-sensitive indicator labels, to confirm that the irradiation process has
      taken place. With the apparent increased use of linear-accelerators to irradiate
      blood components, appropriate quality assurance measures need to be developed.
      The maximum storage period for irradiated red cells should be shorter than for
      nonirradiated red cells if the treatment is performed early during the storage
      period because irradiation reduces the in vivo 24-hour red cell recovery
      parameter. The storage period for irradiated platelets does not need to be
      modified. Some questions are being raised regarding whether fresh-frozen plasma
      should be irradiated to inactivate a small number of immunocompetent progenitor
      cells that may be present. Table 4 summarizes the practices that should be
      followed in connection with the technical issues that have been addressed in this
      article. These guidelines follow the recommendations issued in July 1993 by the
      FDA in the United States. This article and Tables 1 and 2 contain additional
      guidelines.

PMID- 9031488
TI  - Modifying physicians' transfusion practice.

PMID- 9031489
TI  - Comprehensive reimbursement model: an alternative to fee-for-service
      reimbursement by blood centers.
AB  - "If we could first know where we are, and whither we are tending, we could then
      better judge what to do and how to do it." This quote from Abraham Lincoln
      epitomizes where SMF and its CRM hospital customers are today. The CRM has been
      received by SMF's hospital customers as a step in the right direction. Currently,
      it seems to be the best way to partner with hospitals by sharing risk in the
      current health care delivery system milieu. The CRM focus on patient outcomes
      will provide hospitals and blood centers a common goal. Modifications to the CRM
      will most certainly be necessary. With input from customers and the community
      over time, and flexibility from SMF, a revised model will evolve that will be
      even more mutually beneficial.

PMID- 9031490
TI  - Principles of counting low numbers of leukocytes in leukoreduced blood
      components.

PMID- 9031491
TI  - Coagulation factor concentrates by continuous infusion.

PMID- 9031492
TI  - Donor reactions and injuries from whole blood donation.
AB  - In this review of common and uncommon donor reactions and injuries, donation
      associated deaths were found to be extremely rare and generally thought to be
      coincidental; the rate of coincidental deaths was less than what would be
      expected based on life insurance tables. Vasovagal reactions, hematomas/bruises,
      and history of irritation or allergic reaction to adhesive tape or skin
      preparations are observed daily in a busy blood collection center. Syncopal
      vasovagal reactions sometimes resemble shock, but unlike shock, they reverse
      themselves and do not cause death. Through good management, a blood donor
      organization can minimize the incidence of syncope. Accidental arterial
      venipuncture is very uncommon (1 in 100,000), and donors with arterial punctures
      do well if pressure is applied for an extended period of time. Rarely, a
      pseudoaneurysm results, and this requires surgery. AV fistulas and compartment
      syndromes can also occur, but these are extremely rare; most experienced blood
      center physicians have never observed a case. Neurologic needle injuries occur
      approximately once in every 6,300 donations. Although neurologic needle injury
      complaints are usually received within 10 days of blood donation, 10% of the
      injured donors may complain weeks to months later. Most donors with needle
      injuries recover within a month and many within a day or two, but approximately
      30% will have a recovery period of greater than 1 month and an occasional case
      may exceed 6 months. Donors with neurologic needle injuries generally have a full
      recovery, even when the recovery period may be extended. Thrombophlebitis has a
      low incidence (1 in 50,000 to 1 in 100,000), and infection at the phlebotomy site
      is rare. Both are easily treated and have little impact on the donor's health.

PMID- 9031493
TI  - Human parvovirus B19 and blood products.
AB  - BACKGROUND AND OBJECTIVES: Human B19 parvovirus (B19), identified in 1975, was
      only recognised as the causative agent of fifth disease in 1983. The incidence of
      viraemia is low, around 1 in 1,000, but is sufficient to ensure that most plasma
      pools for fractionation contain some virus. While infection usually occurs in
      childhood and is benign, chronic infection sometimes occurs and may be of concern
      in certain patient groups. MATERIALS AND METHODS: This review is based on a
      meeting held in March 1995, and addresses recent concerns regarding the potential
      transmission of B19 infection by pooled plasma products. RESULTS: Recent data on
      the pathophysiology and assay of this virus are summarised along with possible
      approaches to donor screening, product screening, and virus removal. Only five
      cases of symptomatic infection have been reported in persons with haemophilia,
      but no technology for virus removal is established, and infection may be of
      concern in pregnant women, and in patients with enhanced red cell turnover or who
      are immunosuppressed, including those infected with human immunodeficiency virus,
      but only rarely in immunocompetent patients. CONCLUSIONS: For the future, well
      validated assays relevant to virus infectivity are required if blood donations,
      plasma pools, or plasma products are to be screened, and an in-process virus
      inactivation step for B19 would be highly desirable. In the interim, non-plasma
      or recombinant products or a selective transfusion policy might be used in
      patient groups in which B19 infection is of particular concern. Further clinical
      data on the prognosis and impact of B19 infection are needed to justify both such
      policies and the future adoption of new technologies designed to reduce any
      excess B19 infectivity arising from transfused products.

PMID- 9031494
TI  - Sensitivity and specificity of standard and rapid HIV-antibody tests evaluated by
      seroconversion and non-seroconversion low-titre panels.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study is to compare the relative
      sensitivity and specificity of commercial HIV-antibody assays using
      seroconversion, non-seroconversion panels, and negative blood donor samples.
      MATERIALS AND METHODS: We evaluated the sensitivity of five standard ELISA HIV
      antibody assays: Vironostika HIV Uni-Form II, Abbott recombinant HIV-1/HIV-2
      third-generation EIA, Biotest Anti-HIV-1/-2 recombinant, Recombigen HIV-1/ HIV-2
      EIA and Wellcozyme HIV 1 + 2 (VK54/55), and three rapid screening tests, Capillus
      HIV-1/HIV-2, Abott Test Pack HIV-1/HIV-2 third-generation EIA, and Sensy-Test HIV
      1/2. All tests were assessed using four panels of plasma samples obtained from
      individuals who were seroconverting and a low-titre HIV-antibody panel of
      samples. Specificity of the standard screening tests was determined on 3.500 HIV
      antibody-negative blood donor samples. RESULTS: There was no statistically
      significant difference in sensitivity between the five standard ELISA tests. One
      of these tests was significantly less specific than the others. The standard
      ELISA tests detected all the low-titre HIV-antibody-positive samples. Two of the
      rapid screening tests were significantly less sensitive on the seroconversion
      panels and all three tests failed to detect at least one of the positive samples
      in the low-titre panel. CONCLUSIONS: The additional risk of using one or other of
      the standard ELISA tests under review of not detecting all HIV-positive units of
      blood is not statistically significant. Using some of the rapid screening tests
      will, however, add a significant additional risk. A rapid screening test should
      therefore be adopted only after careful consideration of the effect of a possible
      lack of sensitivity on the safety of the blood supply.

PMID- 9031495
TI  - Influence of antioxidants on the quality of stored blood.
AB  - BACKGROUND AND OBJECTIVES: Blood is exposed to oxidation stress and therefore has
      a high antioxidant capacity (AOC). With the many factors increasing the demands
      on the AOC, there may be damage to erythrocytes by free radicals. This study was
      to investigate evidence of erythrocyte damage in stored donor blood and to affect
      this by premedication of blood donors. MATERIALS AND METHODS: Blood samples of 15
      healthy donors were collected in CPDA-1 solution and analyzed immediately, and
      then again after 10 days of incubation at 4 degrees C and 1 day of incubation at
      37 degrees C. Prior to incubation, the following parameters were evaluated: Na+,
      K+, malondialdehyde (MDA), hemoglobin (Hb), AOC in the supernatant, superoxide
      dismutase (SOD) in erythrocytes, and glutathione peroxidase (GSHPx) in whole
      blood. Blood donors of group 1 were not given any drugs or vitamins before blood
      sampling. The same blood donors were then supplemented with the following daily
      doses of antioxidants for 10 days before the next blood sampling: 36 mg of beta
      carotene, 300 mg of vitamin E, 200 mg of vitamin C, and 40 mg of selenium.
      RESULTS: The blood from donors of group 2 had a significantly smaller increase in
      MDA, K+, and Hb, and a smaller decrease in Na+ and AOC in the supernatant
      compared with that of group 1, while the activity of SOD and GSHPx did not change
      during blood storage. CONCLUSIONS: These results suggest that antioxidants given
      to blood donors can improve red cell storage parameters by reducing cell damage
      caused by free radicals.

PMID- 9031496
TI  - Leukocyte depletion and storage of single-donor platelet concentrates.
AB  - BACKGROUND AND OBJECTIVES: Because of widespread use of leukocyte reduction in
      platelet concentrates (PCs) and the need to store such concentrates, we
      investigated the effects of leukocyte depletion on the quality of stored PCs.
      MATERIALS AND METHODS: Ten double-sized PCs were divided into 2 equal units which
      were tested simultaneously. One half was stored for 5 days after filtration
      through a polyester filter, the other one was stored unfiltered. RESULTS: The
      volume of the 10 "oversized' PCs was 483 +/- 40 ml (mean +/- standard deviation)
      and they contained 5.9 +/- 1.5 x 10(11) platelets and 80 +/- 23 x 10(6)
      leukocytes. Filtration significantly reduced the leukocyte concentration (168 +/-
      56/microliter before, 6 +/- 4 /microliter after filtration) and leukocyte count
      (39.9 +/- 11.3 x 10(6) vs. 1.3 +/- 0.9 x 10(6); p < 0.0005). Filtration caused a
      platelet loss of 16%, the platelet count decreasing not significantly from 2.91
      +/- 0.75 x 10(11) to 2.40 +/- 0.94 x 10(11) (p = 0.26). After 5 days of storage
      all parameters of platelet function (platelet aggregation to several stimuli,
      hypotonic shock reaction [HSR] and platelet retraction), mean platelet volume,
      and pH and pCO2 showed no advantage for PCs filtered prior to storage compared to
      PCs stored unfiltered. Moreover, platelet aggregation on day 5 using 4 agonists
      at 10 concentrations showed worse results in 4 assays in prestorage filtered PCs
      (collagen [4 micrograms/ml: p < 0.05, ADP [0.2 mM]: p < 0.05, ADP [0.3 mM]: p <
      0.05, thrombin [0.6 E/ml]: p < 0.05). But there is no convincing trend in all
      aggregation tests, and HSR, presumably the most useful parameter, was not
      different or day 5. CONCLUSIONS: There is no advantage in terms of improved
      quality for prestorage leuko-depletion of PCs. Taking into account the obvious
      disadvantages of filtration, such as platelet loss and increasing costs per
      transfusion, we conclude that pre- or post-storage filtration of single-donor PCs
      should be done only for patients who have a clear indication for the transfusion
      of leukocyte-poor blood products.

PMID- 9031497
TI  - A monolayer coagglutination microplate technique for typing red blood cells.
AB  - BACKGROUND AND OBJECTIVES: Serologic agglutination tests have the disadvantage of
      lack of an objective endpoint that can be easily read and quantitated. We have
      developed a new method for ABO and Rh typing based on producing a red blood cell
      (RBC) monolayer on microplates and the mixed hemagglutination reaction. MATERIALS
      AND METHODS: We have employed a new red cell fixation buffer to prepare the RBC
      monolayer. As the technique for grouping, we used a mixed agglutination reaction
      between the RBC monolayer and the RBCs to be typed. RESULTS: Compared with an
      automated hemagglutination system in 34,519 samples, the method is shown to be
      more sensitive, free of false positive reactions, and cost-effective.
      CONCLUSIONS: The microplate coagglutination method is accurate and lower in cost
      than conventional methods.

PMID- 9031498
TI  - Two missense mutations of H type alpha(1,2)fucosyltransferase gene (FUT1)
      responsible for para-Bombay phenotype.
AB  - BACKGROUND AND OBJECTIVES: Rare individuals (Bombay and para-Bombay phenotypes)
      fail to express the A, B and H antigens on erythrocyte membranes because of a
      lack in the H gene (FUT1)-encoded alpha(1,2)fucosyltransferase activity. In this
      study, we have found a para-Bombay individual (Bmh) who expressed B and H
      antigens in saliva but not on red blood cells. The FUT1 alleles of this person
      contained two single base changes (T460C and G1042A) in the coding region
      relative to the wild type allele. These substitutions may result in changes in
      two amino acid residues (Y154H and E348K). MATERIALS AND METHODS: Since the T460C
      and G1042A mutations destroy endonuclease RsaI and AvaI sites, respectively, we
      tested for these mutations using PCR-RFLP. RESULTS: Our findings indicated that
      this para-Bombay person was homozygous for the T460C and G1042A mutations, and
      that neither of these mutations was found in 136 randomly selected Japanese
      individuals. The measurement of the alpha(1,2)fucosyltransferase activity after
      transient expression of the FUT1 alleles in COS-7 cells indicated that the H
      deficient allele-encoded enzyme had no detectable activity. Moreover,
      transfection by chimera FUT1 allele contains only the T460C mutation, or only the
      G1042A mutation, and yielded 1.0 or 9.3%, respectively, of the activities
      compared to transfection by the wild type allele. CONCLUSIONS: These results
      suggest that the two mutations in combination are responsible for the
      inactivation of the FUT1-encoded enzyme activity.

PMID- 9031499
TI  - Heterogeneity of the human H blood group alpha(1,2)fucosyltransferase gene among
      para-Bombay individuals.
AB  - BACKGROUND AND OBJECTIVES: The para-Bombay phenotype has a relatively high
      frequency of about 1 in 8,000 Taiwanese. Studies were carried out on eight
      healthy and unrelated Taiwanese with the para-Bombay phenotype to cast light on
      its immunogenetic basis. MATERIALS AND METHODS: Blood and saliva samples were
      tested with standard hemagglutination techniques. Salivary ABH substances were
      determined by hemagglutination inhibition. PCR techniques were used to amplify
      the coding region of the H genes. RESULTS: Five different h alleles, designated
      as h1, h2, h3, h4 and h5, were identified in the Taiwanese with the para-Bombay
      phenotype. The h1 allele loses one of the three AG repeats located at the
      nucleotides 547-552 of the H gene, whereas two of the three T repeats located at
      the nucleotides 880-882 are deleted in the h2 allele. The h3 allele contains a
      C658 to T missense mutation, whereas two missense mutations, C35 to T and A980 to
      C were identified in the h4 allele. A T460 to C missense is present in the h5
      allele. The h5 allele was identified in an individual whose red blood cells
      contain blood group A antigen but not H antigen, and thus may be considered a
      weak variant of the H gene. CONCLUSIONS: So far no biologic relevance of the H
      antigen has been discovered, and its deficiency does not seem to produce any
      deleterious effects. There may be better understanding of the evolutionary basis
      for the polymorphisms at these loci after systematic study of different ethnic
      populations.

PMID- 9031500
TI  - Rh haplotypes that make e but not hrB usually make VS.
AB  - BACKGROUND AND OBJECTIVES: The Rh phenotypes hrB- and VS+ are both rare in Whites
      but more common in Blacks. The high-incidence antigen hrB is present on most red
      cells that are e+. The presence of VS on red cells is associated with an aberrant
      expression of e, often called eS. MATERIALS AND METHODS: Using conventional
      serologic methods, including a monoclonal anti-hrB-like antibody, we studied 65
      e+ samples that were apparently hrB-. RESULTS: Of the 65, we found that 59 (91%)
      were VS+. Recent findings have indicated that in VS+ persons a change from
      leucine to valine occurs at amino acid 245 of the RHCE-encoded polypeptide. While
      this residue is predicted to lie within the red cell membrane bilayer, the change
      presumably affects alanine 226 (that is present when e is expressed) in such a
      way that eS is seen. CONCLUSIONS: Our findings suggest that the change from e to
      eS may result in nonexpression or marked depression of expression of hrB that is,
      perhaps, an epitope of e. While the molecular basis of the hrB-phenotype is not
      known, it is unlikely that the leucine-to-valine change at residue 245, resulting
      in the aberrant from of e, explains all hrB-samples. First, hrB-VS+ and hrB- VS-
      samples must differ. Second, some hrB- VS+ samples are C+, some are C-.
      Presumably diverse molecular bases are involved in hrB-phenotypes.

PMID- 9031501
TI  - In vitro functional activity of IgG1 and IgG3 polyclonal and monoclonal anti-D.
AB  - BACKGROUND AND OBJECTIVES: IgG anti-D is generally restricted to IgG1 and IgG3;
      it mediates red cell destruction through interactions with IgG Fc receptors (Fc
      gamma R) on effector cells. The relative ability of these two IgG subclasses of
      anti-D to mediate haemolysis in vitro by monocytes and K cells was investigated.
      MATERIALS AND METHODS: Anti-D was affinity purified from 5 preparations of
      prophylactic anti-D immunoglobulin, and IgG subclasses quantified by ELISA; mean
      levels were 86.5% IgG1, 1.4% IgG2, 11.6% IgG3 and 0.4% IgG4. IgG1 and IgG3
      polyclonal anti-D were further purified separately from some of the anti-D by
      removal of either IgG3 using magnetic beads coated with anti-IgG3, or of IgG1
      using protein A. These preparations were compared with monoclonal anti-D (BRAD-3
      and BRAD-5) for their ability to lyse red cells in antibody-dependent cell
      mediated cytotoxicity (ADCC) assays. RESULTS: Monocyte-mediated lysis of red
      cells coated with IgG3 anti-D was approximately twice that of cells coated with
      IgG1 anti-D at similar sensitization levels, and anti-D preparations containing
      10% or more IgG3 gave similar lysis. By contrast, in the K cell ADCC, IgG1 anti-D
      was 2-4 times more haemolytic than IgG3 anti-D. Polyclonal IgG1 and IgG3 anti-D
      promoted about 20% more lysis than BRAD-5 (IgG1) and BRAD-3 (IgG3), respectively,
      in the K cell ADCC, although no difference was observed between polyclonal and
      monoclonal anti-D in the monocyte ADCC. CONCLUSIONS: These experiments
      demonstrated a functional dichotomy between these two subclasses of anti-D; IgG3
      coated red cells were lysed preferentially by monocytes mediated predominantly
      through Fc gamma R1 interactions, whereas haemolysis of IgG1-sensitized cells was
      mediated mainly by Fc gamma RIII on K cells.

PMID- 9031502
TI  - Human monoclonal Fab fragments recovered from a combinatorial library bind
      specifically to the platelet HPA-1a alloantigen on glycoprotein IIb-IIIa.
AB  - BACKGROUND AND OBJECTIVES: Certain clinical conditions are related to the
      presence of platelet-specific alloantibodies in the patient's serum. We studied
      the molecular diversity of HPA-1a antibodies to analyze some peculiarities of
      this antibody response. MATERIALS AND METHODS: Human antibody Fab fragments that
      bind to the platelet alloantigen HPA-1a on glycoprotein IIb-IIIa (GPIIbIIIa) were
      generated by using a recombinant phage display system. We established an
      immunoglobulin G1, kappa combinatorial library from the peripheral blood
      lymphocytes of a person undergoing a severe posttransfusion purpura. RESULTS:
      Characterization of Fab clones selected from the fifth round of antigen-specific
      panning of this library demonstrates a highly specific reactivity to the HPA-1a
      alloantigen. The nucleotide sequence analysis of representative HPA-la-specific
      clones reveals at least 3 distinct V1 and 3VH gene segments that present an
      extensive degree of mutation as demonstrated by comparison of gene usage and
      homologies to the nearest germline genes. CONCLUSIONS: These human HPA-la
      specific Fab reagents should allow us to better understand the molecular
      mechanism involved in HPA-la alloimmunization.

PMID- 9031503
TI  - Sterility testing of blood products in 1994/1995 by three cooperating blood banks
      in The Netherlands.
AB  - BACKGROUND AND OBJECTIVES: Dutch regulations require blood banks to check the
      sterility of random blood components to detect contamination during preparation.
      MATERIALS AND METHODS: We reviewed the results of two years' testing, using
      standard bacteriologic methods. RESULTS: Of all tested components, 0.5% were
      contaminated, with Staphylococcus epidermidis being the most frequently detected
      microorganism. Platelet concentrates showed higher rates of contamination,
      especially when pooled. Leukocyte-depleted red cell concentrates showed much
      lower contamination than red cell concentrates that had not been leuko-depleted.
      CONCLUSIONS: The rate of contamination compares well with that reported by others
      in the literature. Since most contamination occurs from the phlebotomy site, most
      of the bacteria detected were derived from the skin. Leukocyte reduction lowers
      the rate of contamination.

PMID- 9031504
TI  - Hepatitis C virus genotypes--mixed infections.

PMID- 9031506
TI  - Neutron anatomy.
AB  - The familiar extremes of crystalline material are single-crystals and random
      powders. In between these two extremes are polycrystalline aggregates, not
      randomly arranged but possessing some preferred orientation and this is the form
      taken by constructional materials, be they steel girders or the bones of a human
      or animal skeleton. The details of the preferred orientation determine the
      ability of the material to withstand stress in any direction. In the case of bone
      the crucial factor is the orientation of the c-axes of the mineral content-the
      crystals of the hexagonal hydroxyapatite- and this can readily be determined by
      neutron diffraction. In particular it can be measured over the volume of a piece
      of bone, utilising distances ranging from 1 mm to 10 mm. The major practical
      problem is to avoid the intense incoherent scattering from the hydrogen in the
      accompanying collagen; this can best be achieved by heat-treatment and it is
      demonstrated that this does not affect the underlying apatite. These studies of
      bone give leading anatomical information on the life and activities of humans and
      animals-including, for example, the life history of the human femur, the
      locomotion of sheep, the fracture of the legs of racehorses and the life-styles
      of Neolithic tribes. We conclude that the material is placed economically in the
      bone to withstand the expected stresses of life and the environment. The
      experimental results are presented in terms of the magnitude of the 0002 apatite
      reflection. It so happens that for a random powder the 0002, 1121 reflections,
      which are neighbouring lines in the powder pattern, are approximately equal in
      intensity. The latter reflection, being of manifold multiplicity, is scarcely
      affected by preferred orientation so that the numerical value of the 0002/1121
      ratio serves quite accurately as a quantitative measure of the degree of
      orientation of the c-axes in any chosen direction, for a sample of bone.

PMID- 9031505
TI  - Neutrons in biology. A perspective.

PMID- 9031507
TI  - Small-angle neutron scattering instrument of institute for solid state physics,
      the University of Tokyo (SANS-U) and its application to biology.
AB  - A small-angle neutron spectrometer (SANS-U) suitable for the study of mesoscopic
      structure in the field of polymer chemistry and biology, has been constructed at
      the guide hall of JRR-3M reactor at the Japan Atomic Energy Research Institute.
      The instrument is 32m long and utilizes a mechanical velocity selector and
      pinhole collimation to provide a continuous beam with variable wavelength in the
      range from 5 to 10 A. The neutron detector is a 65 x 65 cm2 2D position sensitive
      proportional counter. The practical Q range of SANS-U is 0.0008 to 0.45 A-1. The
      design, characteristics and performance of SANS-U are described with some
      biological studies using SANS-U.

PMID- 9031509
TI  - The structure of the muscle protein complex 4Ca2+.troponin C.troponin I. Monte
      Carlo modeling analysis of small-angle X-ray data.
AB  - Analysis of scattering data based on a Monte Carlo integration method was used to
      obtain a low resolution model of the 4Ca2+.troponin C.troponin I complex. This
      modeling method allows rapid testing of plausible structures where the best fit
      model can be ascertained by a comparison between model structure scattering
      profiles and measured scattering data. In the best fit model, troponin I appears
      as a spiral structure that wraps around 4Ca2+.troponin C which adopts an extended
      dumbbell conformation similar to that observed in the crystal structures of
      troponin C. The Monte Carlo modeling method can be applied to other biological
      systems in which detailed structural information is lacking.

PMID- 9031508
TI  - Neutron scattering studies on chromatin higher-order structure.
AB  - We have been engaged in studies of the structure and condensation of chromatin
      into the 30 nm filament using small-angle neutron scattering. We have also used
      deuterated histone H1 to determine its location in the chromatin 30 nm filament.
      Our studies indicate that chromatin condenses with increasing ionic strength to a
      limiting structure that has a mass per unit length of 6-7 nucleosomes/11 nm. They
      also show that the linker histone H1/H5 is located in the interior of the
      chromatin filament, in a position compatible with its binding to the inner face
      of the nucleosome. Analysis of the mass per unit length as a function of H5
      stoichiometry suggests that 5-7 contiguous nucleosomes need to have H5 bound
      before a stable higher order structure can exist.

PMID- 9031510
TI  - Structural model of the 50S subunit of E. coli ribosomes from solution
      scattering.
AB  - The application of new methods of small-angle scattering data interpretation to a
      contrast variation study of the 50S ribosomal subunit of Escherichia coli in
      solution is described. The X-ray data from contrast variation with sucrose are
      analyzed in terms of the basic scattering curves from the volume inaccessible to
      sucrose and from the regions inside this volume occupied mainly by RNA and by
      proteins. From these curves models of the shape of the 50S and its RNA-rich core
      are evaluated and positioned so that their difference produces a scattering curve
      which is in good agreement with the scattering from the protein moiety. Based on
      this preliminary model, the X-ray and neutron contrast variation data of the 50S
      subunit in aqueous solutions are interpreted in the frame of the advanced two
      phase model described by the shapes of the 50S subunit and its RNA-rich core
      taking into account density fluctuations inside the RNA and the protein moiety.
      The shape of the envelope of the 50S subunit and of the RNA-rich core are
      evaluated with a resolution of about 40 A. The shape of the envelope is in good
      agreement with the models of the 50S subunit obtained from electron microscopy on
      isolated particles. The shape of the RNA-rich core correlates well with the model
      of the entire particle determined by the image reconstruction from ordered sheets
      indicating that the latter model which is based on the subjective contouring of
      density maps is heavily biased towards the RNA.

PMID- 9031511
TI  - Probing self assembly in biological mixed colloids by SANS, deuteration, and
      molecular manipulation.
AB  - Small-angle neutron scattering was used to obtain information on the form and
      molecular arrangement of particles in mixed colloids of bile salts with
      phosphatidylcholine, and bile salts with monoolein. Both types of systems showed
      the same general characteristics. The particle form was highly dependent on total
      lipid concentration. At the highest concentrations the particles were globular
      mixed micelles with an overall size of 50A. As the concentration was reduced the
      mixed micelles elongated, becoming rodlike with diameter about 50A. The rods had
      a radial core-shell structure in which the phosphatidylcholine or monoolein fatty
      tails were arranged radially to form the core with the headgroups pointing
      outward to form the shell. The bile salts were at the interface between the shell
      and core with the hydrophilic parts facing outward as part of the shell. The
      lengths of the rods increased and became more polydispersed with dilution. At
      sufficiently low concentrations the mixed micelles transformed into single
      bilayer vesicles. These results give insight on the physiological function of
      bile and on the rules governing the self assembly of bile particles in the
      hepatic duct and the small intestine.

PMID- 9031512
TI  - Neutron diffraction studies of amphipathic helices in phospholipid bilayers.
AB  - The structural feature which is thought to facilitate the interaction of many
      peptides with phospholipid bilayers is the ability to fold into an amphipathic
      helix. In most cases the exact location and orientation of this helix with
      respect to the membrane is not known, and may vary with factors such as pH and
      phospholipid content of the bilayer. The growing interest in this area is
      stimulated by indications that similar interactions can contribute to the binding
      of certain hormones to their cell-surface receptors. We have been using the
      techniques of neutron diffraction from stacked phospholipid bilayers in an
      attempt to investigate this phenomenon with a number of membrane-active peptides.
      Here we report some of our findings with three of these: the bee venom melittin;
      the hormone calcitonin; and a synthetic peptide representing the ion channel
      fragment of influenza A M2 protein.

PMID- 9031513
TI  - Neutron reflectivity studies of single lipid bilayers supported on planar
      substrates.
AB  - Neutron reflectivity was used to probe the structure of single
      phosphatidylcholine (PC) lipid bilayers adsorbed onto a planar silicon surface in
      an aqueous environment. Fluctuations in the neutron scattering length density
      profiles perpendicular to the silicon/water interface were determined for
      different lipids as a function of the hydrocarbon chain length. The lipids were
      studied in both the gel and liquid crystalline phases by monitoring changes in
      the specularly-reflected neutron intensity as a function of temperature. Contrast
      variation of the neutron scattering length density was applied to both the lipid
      and the solvent. Scattering length density profiles were determined using both
      model-independent and model-dependent fitting methods. During the reflectivity
      measurements, a novel experimental set-up was implemented to decrease the
      incoherent background scattering due to the solvent. Thus, the reflectivity was
      measured to Q approximately 0.3 A-1, covering up to seven orders of magnitude in
      reflected intensity, for PC bilayers in D2O and silicon-matched (38% D2O/62% H2O)
      water. The kinetics of lipid adsorption at the silicon/water interface were also
      explored by observing changes in the reflectivity at low Q values under silicon
      matched water conditions.

PMID- 9031514
TI  - Intercalation of small hydrophobic molecules in lipid bilayers containing
      cholesterol.
AB  - Partitioning of small hydrophobic molecules into lipid bilayers containing
      cholesterol has been studied using the 2XC diffractometer at the University of
      Missouri Research Reactor. Locations of the compounds were determined by Fourier
      difference methods with data from both deuterated and undeuterated compounds
      introduced into the bilayers from the vapor phase. Data fitting procedures were
      developed for determining how well the compounds were localized. The compounds
      were found to be localized in a narrow region at the center of the hydrophobic
      layer, between the two halves of the bilayer. The structures are therefore
      intercalated structures with the long axis of the molecules in the plane of the
      bilayer.

PMID- 9031515
TI  - Theoretical description of biomolecular hydration. Application to A-DNA.
AB  - The local density of water molecules around a biomolecule is constructed from
      calculated two- and three-points correlation functions of polar solvents in water
      using a Potential-of-Mean-Force (PMF) expansion. As a simple approximation, the
      hydration of all polar (including charged) groups in a biomolecule is represented
      by the hydration of water oxygen in bulk water, and the effect of non-polar
      groups on hydration are neglected, except for excluded volume effects. Pair and
      triplet correlation functions are calculated by molecular dynamics simulations.
      We present calculations of the structural hydration for ideal A-DNA molecules
      with sequences [d(CG)5]2 and [d(C5G5)]2. We find that this method can accurately
      reproduce the hydration patterns of A-DNA observed in neutron diffraction
      experiments on oriented DNA fibers (P. Langan et al. J. Biomol. Struct. Dyn., 10,
      489 (1992)).

PMID- 9031517
TI  - Myoglobin solvent structure at different temperatures.
AB  - The structure of the solvent surrounding myoglobin crystals has been analyzed
      using neutron diffraction data, and the results indicate that the water around
      the protein is not disordered, but rather lies in well-defined hydration shells.
      We have analyzed the structure of the solvent surrounding the protein by
      collecting neutron diffraction data at four different temperatures, namely, 80,
      130, 180, and 240K. Relative Wilson Statistics applied to low resolution data
      showed evidence of a phase transition in the region of 180K. A plot of the
      liquidity factor, Bsn, versus distance from the protein surface begins with a
      high plateau near the surface of the protein and drops to two minima at distances
      from the protein surface of about 2.35A and 3.85A. Two distinct hydration shells
      are observed. Both hydration shells are observed to expand as the temperature is
      increased.

PMID- 9031516
TI  - High-level expression and deuteration of sperm whale myoglobin. A study of its
      solvent structure by X-ray and neutron diffraction methods.
AB  - Neutron diffraction has become one of the best ways to study light atoms, such as
      hydrogens. Hydrogen however has a negative coherent scattering factor, and a
      large incoherent scattering factor, while deuterium has virtually no incoherent
      scattering, but a large positive coherent scattering factor. Beside causing high
      background due to its incoherent scattering, the negative coherent scattering of
      hydrogen tends to cancel out the positive contribution from other atoms in a
      neutron density map. Therefore a fully deuterated sample will yield better
      diffraction data with stronger density in the hydrogen position. On this basis, a
      sperm whale myoglobin gene modified to include part of the A c11 protein gene has
      been cloned into the T7 expression system. Milligram amounts of fully deuterated
      holo-myoglobin have been obtained and used for crystallization. The synthetic
      sperm whale myoglobin crystallized in P2(1) space group isomorphous with the
      native protein crystal. A complete X-ray diffraction dataset at 1.5A has been
      collected. This X-ray dataset, and a neutron data set collected previously on a
      protonated carbon-monoxymyoglobin crystal have been used for solvent structure
      studies. Both X-ray and neutron data have shown that there are ordered hydration
      layers around the protein surface. Solvent shell analysis on the neutron data
      further has shown that the first hydration layer behaves differently around polar
      and apolar regions of the protein surface. Finally, the structure of per
      deuterated myoglobin has been refined using all reflections to a R factor of 17%.

PMID- 9031518
TI  - Determination of protein and solvent volumes in protein crystals from contrast
      variation data.
AB  - By varying the relative values of protein and solvent scattering densities in a
      crystal, it is possible to obtain information on the shape and dimensions of
      protein molecular envelopes. Neutron diffraction methods are ideally suited to
      these contrast variation experiments because H/D exchange leads to large
      differential changes in the protein and solvent scattering densities and is
      structurally non-perturbing. Low resolution structure factors have been measured
      from cubic insulin crystals with differing H/D contents. Structure factors
      calculated from a simple binary density model, in which uniform scattering
      densities represent the protein and solvent volumes in the crystals, were
      compared with these data. The contrast variation differences in the sets of
      measured structure factors were found to be accurately fitted by this simple
      model. Trial applications to two problems in crystal structure determination
      illustrate how this fact may be exploited. (i) A translation function that
      employs contrast variation data gave a sharp minimum within 1-9A of the correctly
      positioned insulin molecule and is relatively insensitive to errors in the atomic
      model. (ii) An ab initio phasing method for the contrast variation data, based on
      analyzing histograms of the density distributions in trial maps, was found to
      recover the correct molecular envelope.

PMID- 9031519
TI  - DNA hydration studied by neutron fiber diffraction.
AB  - The development of neutron high angle fiber diffraction to investigate the
      location of water around the deoxyribonucleic acid (DNA) double-helix is
      described. The power of the technique is illustrated by its application to the D
      and A conformations of DNA using the single crystal diffractometer, D19, at the
      Institut Laue-Langevin. Grenoble and the time of flight diffractometer, SXD, at
      the Rutherford Appleton ISIS Spallation Neutron Source. These studies show the
      existence of bound water closely associated with the DNA. The patterns of
      hydration in these two DNA conformations are quite distinct and are compared to
      those observed in X-ray single crystal studies of two-stranded
      oligodeoxynucleotides. Information on the location of water around the DNA double
      helix from the neutron fiber diffraction studies is combined with that on the
      location of alkali metal cations from complementary X-ray high angle fiber
      diffraction studies at the Daresbury Laboratory SRS using synchrotron radiation.
      These analyses emphasize the importance of viewing DNA, water and ions as a
      single system with specific interactions between the three components and provide
      a basis for understanding the effect of changes in the concentration of water and
      ions in inducing conformational transitions in the DNA double-helix.

PMID- 9031520
TI  - Time-of-flight Laue fiber diffraction studies of perdeuterated DNA.
AB  - The diffractometer SXD at the Rutherford Appleton Laboratory ISIS pulsed neutron
      source has been used to record high resolution time-of-flight Laue fiber
      diffraction data from DNA. These experiments, which are the first of their kind,
      were undertaken using fibers of DNA in the A conformation and prepared using
      deuterated DNA in order to minimise incoherent background scattering. These
      studies complement previous experiments on instrument D19 at the Institut Laue
      Langevin using monochromatic neutrons. Sample preparation involved drawing large
      numbers of these deuterated DNA fibers and mounting them in a parallel array. The
      strategy of data collection is discussed in terms of camera design, sample
      environment and data collection. The methods used to correct the recorded time-of
      flight data and map it into the final reciprocal space fiber diffraction dataset
      are also discussed. Difference Fourier maps showing the distribution of water
      around A-DNA calculated on the basis of these data are compared with results
      obtained using data recorded from hydrogenated A-DNA on D19. Since the methods
      used for sample preparation, data collection and data processing are
      fundamentally different for the monochromatic and Laue techniques, the results of
      these experiments also afford a valuable opportunity to independently test the
      data reduction and analysis techniques used in the two methods.

PMID- 9031521
TI  - The chemical reactivity and structure of collagen studied by neutron diffraction.
AB  - The chemical reactivity of collagen can be studied using neutron diffraction (a
      non-destructive technique), for certain reaction types. Collagen contains a
      number of lysine and hydroxylysine side chains that can react with aldehydes and
      ketones, or these side chains can themselves be converted to aldehydes by lysyl
      oxidase. The reactivity of these groups not only has an important role in the
      maintenance of mechanical strength in collagen fibrils, but can also manifest
      pathologically in the cases of aging, diabetes (reactivity with a variety of
      sugars) and alcoholism (reactivity with acetaldehyde). The reactivity of reducing
      groups with collagen can be studied by neutron diffraction, since the crosslink
      formed in the adduction process is initially of a Schiff base or keto-imine
      nature. The nature of this crosslink allows it to be deuterated, and the position
      of this relatively heavy scattering atom can be used in a process of phase
      determination by multiple isomorphous replacement. This process was used to study
      the following: the position of natural crosslinks in collagen; the position of
      adducts in tendon from diabetic rats in vivo and the in vitro position of
      acetaldehyde adducts in tendon.

PMID- 9031522
TI  - In situ shape and distance measurements in neutron scattering and diffraction.
AB  - Neutron scattering combined with selective isotopic labeling and contrast
      matching is useful for obtaining in situ structural information about a selected
      particle, or particles, in a macromolecular complex. The observed intensities,
      however, may be distorted by inter-complex interference and by scattering-length
      density fluctuations of the (otherwise) contrast-matched portions. Methods have
      been proposed to cancel out such distortions (Hoppe's method, the Statistical
      Labeling Method, and the Triple Isotopic Substitution Method). With these methods
      as well as related unmixed-sample methods, structural information about the
      selected particle(s) can be obtained without these distortions. We have
      generalized these methods so that, in addition to globular particles in solution,
      they can be applied to in situ structures of systems having underlying symmetry
      and/or net orientation as well. The information obtainable from such experiments
      is discussed.

PMID- 9031523
TI  - Xylaramide, a new antifungal compound, and other secondary metabolites from
      Xylaria longipes.
AB  - Xylaramide (1), possessing potent antifungal activity towards Nematospora coryli
      and Saccharomyces cerevisiae, was isolated from the culture fluids of the wood
      inhabiting ascomycete Xylaria longipes together with tyrosol (2), 2,5
      bis(hydroxymethyl)furan (3) and 2-hexyli-dene-3-methylsuccinic acid (4). The
      latter has been known as a Xylaria metabolite for many years. Compounds 2 and 3
      have been previously reported from other fungi, whereas 1 is a new natural N-(2
      phenylethenyl)-2-hydroxypropanamide. The isolation, structure determination and
      biological properties of xylaramide are described. The biological activities of
      the other compounds are included.

PMID- 9031524
TI  - Localization of benzoxazinones that occur constitutively in wheat seedlings.
AB  - Occurrence and localization of novel antimicrobial and antifeeding compounds in
      wheat, 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) and 2,4-dihydroxy-7-methoxy-1,4
      benzoxazin-3-one (DIMBOA), and their glucosides, were examined by staining wheat
      plants (Triticum aestivum L.) in the juvenile stage of growth by ferric chloride.
      The methanol extracts of the stained plant tissues gave a characteristic blue
      color, which was shown by spectroscopic and chromatographic analyses to be
      exclusively due to benzoxazinones. When ferric chloride was applied to the root
      in the seedlings, the blue color immediately developed, the staining being
      strongest at the tip region and becoming lighten towards the basal part. The
      staining pattern of the radicle in the pre-emerging seed was similar to that in
      the root, but the coleorhiza was not stained. Little staining was observed in the
      epidermal layer of the leaf sheath in the shoot but the underlying tissue was
      stained strongly. The foliage leaf folded in the sheath was also stained, but
      less intense than the shealth tissue. It is suggested that the DIBOA and DIMBOA
      are produced within the stained region of the leaf and root. Together with
      previous findings that the benzoxazinones appear constitutively in wheat during
      the juvenile stage of growth. their localized occurrence in the tissues exposed
      to microbial and insect attacks suggests that they act as defense compounds
      during this vulnerable plant stage.

PMID- 9031525
TI  - Temperature dependence of the O2-oscillation pattern in the filamentous
      cyanobacterium Oscillatoria chalybea and in Chlorella kessleri.
AB  - Five characteristic discontinuities of the pattern of oxygen evolution have been
      detected for the filamentous cyanobacterium Oscillatoria chalybea in the
      temperature range of 0 degree C to 30 degrees C. The temperatures at which these
      discontinuities occur are: approximately 5 degrees C, approximately 11 degrees C,
      approximately 15 degrees C, approximately 21 degrees C and approximately 25
      degrees C. The calculated initial 5-S state distribution, the miss parameter and
      the fraction of the fast transition S3-->So + O2 are affected. The
      discontinuities are observed at the same transition temperature also for
      Chlorella kessleri hence are not specific for the cyanobacterium. Based on these
      studies it is concluded that the not vanishing oxygen signal under the first
      flash of a flash train in Oscillatoria cannot have its origin in interactions
      between oxygen-evolving complexes. A decrease of temperature should slow down the
      expected charge exchanges, improve the oscillations thus reduce or lower the
      first two oxygen amplitudes of the oscillatoria pattern. Lowering of the
      temperature improves the oscillations but does not lower the first O2 signal of
      the pattern.

PMID- 9031526
TI  - Bimodal effect of amphiphilic biocide concentrations on fluidity of lipid
      membranes.
AB  - Using the spin label method (ESR) it has been shown that biologically active,
      amphiphilic compounds (quaternary ammonium salts (AS) containing polar heads with
      single and double positive charge caused, at low concentrations, decrease
      fluidity of liposome membranes formed with egg yolk lecithin (EYL). At higher
      concentrations an increase in fluidity was observed. With compounds having a
      single positive charge minimum fluidity of membrane structure occurs in the range
      of 1 to 3%, with compounds containing double positive charge-in the range of 4
      6%. That effect does not depend on polar head size and length of alkyl chains of
      the AS used. Analysis of the electrostatic interaction between positive charges
      and dipole system suggest that at low ion concentrations the binding energy of
      the system increases, while it decreases at high concentrations. For the model
      presented, maximum of binding energy of the system occurs at 3% of positive
      monovalent ions and at 6% of positive divalent ions admixed.

PMID- 9031527
TI  - Nutritional regulation of the activities of lipogenic enzymes of rat liver and
      brown adipose tissue.
AB  - Nutrition-induced effects on the activity of enzymes of lipogenesis, fatty acid
      synthase (FAS: EC 2.3.1.85), ATP citrate lyase (ACL: EC 4.1.3.8), malic enzyme
      (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH: EC 1.1.1.49) and 6
      phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44) were investigated in liver and
      interscapular brown adipose tissue (BAT) of rats. The lipogenic enzymes could be
      grouped into two categories according to their response to dietary manipulations:
      FAS and ACL, both key enzymes of lipogenesis, responded fast and strongly to
      dietary manipulations. ME, G6PDH and PGDH, enzymes which also contribute to
      metabolic pathways other than lipogenesis, responded in a more sustained and less
      pronounced fashion. Feed deprivation caused the specific activities of lipogenic
      enzymes to decline several-fold. Refeeding of previously fasted (up to 3 days)
      animals increased the activities dramatically (10-to 25-fold) to far above pre
      fasting levels ("overshoot"). Repetition of the fasting/refeeding regimen
      increasingly impaired the ability of both tissues to synthesize overshooting
      enzyme activities in the subsequent refeeding period. The fasting-induced decline
      of the activities was prevented when sugars were provided to the animals via
      drinking water. The sugars displayed different effectivities: sucrose = glucose >
      fructose > maltose > > lactose. Sugars as the sole nutrient after fasting were
      also able to induce overshooting enzyme activities. Again, activities of FAS and
      ACL responded in a more pronounced fashion than the other three enzymes.
      Transition from feeding one diet to feeding a new diet of different composition
      led to adaptation of the lipogenic enzyme activities to levels characteristic for
      the new diet. Replacing a low-carbohydrate with a high-carbohydrate diet
      proceeded with major alterations of enzyme activities. This process of attaining
      a new level took up to 20 days and involved pronounced oscillations of the
      specific activities. In contrast, when a high-carbohydrate diet was replaced with
      another diet. particular one high in fat, transition to new enzyme activities was
      completed within 2-3 days and proceeded without oscillations. All dietary
      manipulations caused more pronounced responses in young (35d-old) than in adult
      (180d-old) animals.

PMID- 9031528
TI  - Human neutrophil chemotaxis in response to diepoxides of linolenic acid.
AB  - Diepoxides of linolenic acid were found to be chemoattractants. The concentration
      that produces 50% of maximal chemotaxis was 4.5 10(-7) mol/l for human
      neutrophils when investigated in a chemotaxis test based on the method of
      spectrophotometric determination of myeloperoxidase activity with buffers
      containing bovine serum albumin. Leukotriene B4 was used as positive control. The
      concentration of leukotriene B4 that produces 50% of maximal chemotaxis was 1.8
      nmol/l. No chemotactic activity was observed when monoepoxides of linoleic or
      linolenic acid, diepoxides of linoleic acid or triepoxides of linolenic acid were
      used. Mono-, di- and triepoxides of polyunsaturated fatty acids were synthesized
      with meta-chloroperbenzoic acid, separated by TLC and HPLC and identified by
      GC/MS.

PMID- 9031529
TI  - Inhibition of pancreatic lipase by phenolic acids--examination in vitro.
AB  - The influence of addition 2,4,6,8, and 10 microM of benzoic and cinnamic acids
      and selected phenolic acids (salicylic, p-hydroxybenzoic, gentisic,
      protocatechuic, vanillic, syringic, o-coumaric, p-coumaric, caffeic, ferulic,
      sinapic) on the activity of pancreatic lipase was examined in vitro. The
      strongest inhibition activities were observed with caffeic, ferulic and benzoic
      acid, while sinapic and gentisic acids produced the lowest inhibition.

PMID- 9031530
TI  - Body temperature regulation in heart failure.

PMID- 9031531
TI  - The force-frequency relation in normal and failing heart.

PMID- 9031532
TI  - Time domain signal-averaged electrocardiogram in predicting arrhythmic events
      after myocardial infarction: role of the duration of the filtered QRS complex.
AB  - Several studies showed that time domain analysis of the signal-averaged ECG may
      identify groups of patients with low and high risk for arrhythmic events after
      myocardial infarction (MI). However, the signal averaging methods were not
      uniform and the definition of abnormal signal-averaged ECG was empiric. To
      identify the best quantitative signal-averaged variable in predicting arrhythmic
      events (sustained ventricular tachycardia, ventricular fibrillation and
      witnessed, instantaneous death) 262 patients surviving acute MI were
      prospectively evaluated. Twelve clinical variables, left ventricular ejection
      fraction (LVEF), complex ventricular arrhythmias (CVA) on Holter monitoring and
      three conventional signal-averaged variables (either at 25-250 or 40-250 Hz) were
      entered in a Cox proportional hazards regression model. During a mean follow-up
      of 20.3 +/- 13.7 months 16 (6.1%) patients had arrhythmic events. All six signal
      averaged variables were independent predictors of arrhythmic events and the
      filtered QRS duration (fQRSD) > or = 120 ms at 40 Hz high pass filtering resulted
      the most predictive. In a regression analysis, including the best signal-averaged
      variable, LVEF and CVA, only fQRSD > or = 120 ms at 40 Hz and LVEF independently
      predicted arrhythmic events. Sensitivity, specificity, positive predictive value
      and odds ratio for fQRSD > or = 120 ms at 40 Hz were 63, 90, 29 and 11%,
      respectively, and for the combination of fQRSD > or = 120 ms at 40 Hz and LVEF <
      40%, were 73, 95, 47 and 39%, respectively. In conclusion, the fQRSD > or = 120
      ms at 40 Hz best predicts arrhythmic events in the post-infarction period. The
      combination of signal-averaged ECG and LVEF is recommended to stratify patients
      at risk of arrhythmic events after MI.

PMID- 9031534
TI  - Squamous cell carcinoma of the urethra: ultrasonographic findings.
AB  - Urethral carcinoma is a rare neoplasm and only recently MR imaging has been
      applied to evaluate these tumors. Ultrasonography has mainly been used in the
      evaluation of urethral strictures. In the present paper a patient with squamous
      cell carcinoma of the urethra is reported and findings on ultrasonograms are
      described. Ultrasonography depicted the intraluminal tumor, in contrast to
      retrograde urethrocystograms, which appeared inconspicuous.

PMID- 9031533
TI  - Clinical meaning of ventricular ectopic beats in the diagnosis of HIV-related
      myocarditis: a retrospective analysis of Holter electrocardiographic recordings,
      echocardiographic parameters, histopathological and virologic findings.
AB  - Clinical-pathological studies have demonstrated that in 46-51% of AIDS patients a
      lymphocytic interstitial myocarditis can be found at autopsy. In > 80% of these
      patients no specific etiologic factor for myocarditis was found. This
      pathological finding is believed to be related to a specific pathogenetic action
      of HIV on myocardial tissue and it is called HIV-related myocarditis (HRM). In 15
      30% of patients with lymphocytic interstitial myocarditis ventricular arrhythmias
      have been described. In order to assess the prevalence and the predictive value
      of ventricular ectopic beats (VEB) in the diagnosis of HRM, we performed a
      retrospective analysis of 24-hour Holter recordings, M-mode and two-dimensional
      echocardiographic and Doppler parameters and post-mortem myocardial
      histopathological and virologic findings on a selected sample of 35 NYHA
      functional class II patients died of AIDS. The patients were divided into two
      groups according to post-mortem histopathological findings of myocardium
      specimens: Group 1 (n = 19) including patients with histopathological findings
      consistent with diagnosis of HRM; Group 2 (n = 16), including patients without
      histopathological findings of myocarditis. Group 2 patients represented the
      control group. The retrospective analysis demonstrated a greater prevalence of
      VEB class IV and subclass IVb in Group 1 compared to Group 2 (p = 0.009 and p =
      0.004, respectively). The other classes of VEB did not present a statistically
      significant difference between groups. VEB class IV presented a 81.2% diagnostic
      predictive value (subclass IVa: 50%; subclass IVb: 90.9%). Ejection fraction,
      kinetic score and Doppler E/A ratio, Ei Area, Ai Area and Ai Area/total Area
      ratio and isovolumetric relaxation time were significantly correlated to Lown's
      classes of VEB (p < 0.001) and to the values of CD+ cells (p < 0.001); on the
      other hand, VEB classes correlated significantly with the values of CD+ cells (p
      < 0.001). Syncytial cells and HIV p24 antigen in cultured myocytes were detected
      in 17 Group 1 patients (89.4%) and in 2 Group 2 patients (12.5%; p < 0.001).
      These results have demonstrated that in selected cases of AIDS patients specific
      classes of VEB may represent a simple and sensitive electrocardiographic marker
      of HRM. VEB classes correlate significantly with systolic and diastolic
      echocardiographic parameters and to the values of CD4+ cells. Furthermore, in
      patients with HRM a direct pathogenetic action of HIV may be assumed.

PMID- 9031535
TI  - Aggressive pituitary macroadenoma: CT and MR appearances.
AB  - Two cases of aggressive pituitary macroadenoma (prolactinoma) with diffuse
      invasion of the skull base are described. Clinical signs usually appear late. CT
      shows the bone destruction, whereas MRI accurately delineates the extension of
      the tumor and involvement of the surrounding neurovascular structures.
      Histopathology and immunohistochemical staining are necessary for a definitive
      diagnosis differentiating prolactimonas from a wide range of skull base tumours
      and for deciding on additional therapy and prognosis. Aggressive pituitary
      macroadenoma is a large and diffuse tumor which is difficult to treat; therapy
      usually consists of extensive surgery, radiotherapy and pharmacotherapy with
      dopaminergic agents.

PMID- 9031537
TI  - Enterocolonic fistula, a rare complication of necrotizing enterocolitis.
AB  - A case of an enterocolonic fistula as a late complication of necrotizing
      enterocolitis is presented in a 3-month-old premature baby. The fistula was
      diagnosed by contrast enema. We describe the typical features of this rare
      complication.

PMID- 9031536
TI  - Tongue necrosis as a complication of temporal arteritis: CT and angiographic
      findings.
AB  - We report the case of an 82-year-old woman with probable temporal arteritis
      complicated by extensive tongue necrosis. This severe complication was diagnosed
      on CT; angiography suggested the diagnosis of arteritis.

PMID- 9031538
TI  - Retinoblastoma.

PMID- 9031539
TI  - Urethral saccular diverticulum.

PMID- 9031540
TI  - von Hippel-Lindau disease.

PMID- 9031541
TI  - Blunt abdominal trauma.

PMID- 9031542
TI  - Lipomembranous polycystic osteodysplasia.

PMID- 9031543
TI  - Gastrointestinal metastases of melanoma.

PMID- 9031544
TI  - Pericardial sarcoma.

PMID- 9031545
TI  - Myositis ossificans.

PMID- 9031546
TI  - Spinal abscess.

PMID- 9031547
TI  - Visceral manifestation of AIDS.

PMID- 9031548
TI  - Pseudoaneurysm of the gastrointestinal artery.

PMID- 9031549
TI  - Renal and pulmonary tuberculosis.

PMID- 9031550
TI  - Uterine leiomyoma during pregnancy.

PMID- 9031551
TI  - Eosinophilic granuloma.

PMID- 9031552
TI  - Intrathoracic gallbladder.

PMID- 9031553
TI  - Odontogenic keratocyst.

PMID- 9031554
TI  - Pulmonary air embolism.

PMID- 9031555
TI  - Multilocular renal cell carcinoma.

PMID- 9031556
TI  - Esthesioneuroblastoma.

PMID- 9031557
TI  - Cerebellar agenesis.

PMID- 9031558
TI  - Crohn's disease.

PMID- 9031559
TI  - Pulmonary sarcoidosis.

PMID- 9031560
TI  - Congenital fibromatosis.

PMID- 9031561
TI  - Intraspinal synovial cyst.

PMID- 9031563
TI  - Depression and thyroid.

PMID- 9031562
TI  - Abdominal carcinoid tumor.

PMID- 9031564
TI  - Clonidine side effect.

PMID- 9031565
TI  - Gynecomastia with antipsychotics.

PMID- 9031566
TI  - Viral infection and tic exacerbation.

PMID- 9031567
TI  - Tics with risperidone withdrawal.

PMID- 9031568
TI  - Nonaffective seasonality.

PMID- 9031569
TI  - Infant development and developmental risk: a review of the past 10 years.
AB  - OBJECTIVE: To review critically the research on infant developmental risk
      published in the past 10 years. METHOD: A brief framework on development in the
      first 3 years is provided. This is followed by a review of pertinent studies of
      developmental risk, chosen to illustrate major risk conditions and the protective
      factors known to affect infant development. Illustrative risk conditions include
      prematurity and serious medical illness and infant temperament, infant-caregiver
      attachment, parental psychopathology, marital quality and interactions, poverty
      and social class, adolescent parenthood, and family violence. RESULTS: Risk and
      protective factors interact complexly. There are few examples of specific or
      linear links between risk conditions and outcomes during or beyond the first 3
      years of life. Infant development is best appreciated within the context of
      caregiving relationships, which mediate the effects of both intrinsic and
      extrinsic risk conditions. CONCLUSIONS: Complex and evolving interrelationships
      among risk factors are beginning to be elucidated. Linear models of cause and
      effect are of little use in understanding the development of psychopathology.
      Refining our markers of risk and demonstrating effective preventive interventions
      are the next important challenges.

PMID- 9031570
TI  - Short-term outcome of major depression: I. Comorbidity and severity at
      presentation as predictors of persistent disorder.
AB  - OBJECTIVE: To determine whether there is a pattern of clinical characteristics at
      presentation that specifically predicts persistent major depression at 36 weeks
      follow-up. METHOD: Sixty-eight consecutive cases with a first episode DSM-III-R
      diagnosis of major depression were interviewed with the Schedule for Affective
      Disorders and Schizophrenia for School-Age Children-Present Episode version and
      completed the mood and feelings self-report depression questionnaire (MFQ) at
      presentation and again at 36 weeks. RESULTS: At presentation, 63 (93%) had one or
      more comorbid psychiatric disorders (median = 3). At 36 weeks, 17 (25%) cases
      were recovered; 17 (25%) continued to meet criteria for one or more psychiatric
      disorder but not major depression; 34 (50%) still met criteria for DSM-III-R
      major depression, of whom 25 (73%) had been persistently depressed and 9 (27%)
      had recovered and subsequently relapsed. Major depression at follow-up was
      specifically predicted by the additive effect of three features at presentation,
      comorbid obsessive-compulsive disorder, higher MFQ score, and being older.
      Comorbid oppositional defiant disorder at presentation was a significant
      predictor of persistent psychiatric disorder. Individuals with persistent
      depression (n = 25) were more likely to have a longer duration of illness before
      presentation. CONCLUSION: Systematic assessment of comorbid psychiatric
      conditions at initial interview, together with the use, in older subjects, of a
      self-report questionnaire to determine subjective severity, will provide valid
      clinical information concerning the potential short-term outcome of major
      depression.

PMID- 9031571
TI  - Circadian rest-activity disturbances in children with seasonal affective
      disorder.
AB  - OBJECTIVE: Seasonal affective disorder (SAD) affects from 1.7% to 5.5% of
      children. Previous studies found that nonseasonally depressed children had a
      blunted circadian rhythm, while adults with SAD had a delayed and poorly
      entrained rhythm. The purpose of this study was to determine whether pediatric
      SAD more closely resembles nonseasonal pediatric depression or adult SAD. METHOD:
      Twelve normal, healthy volunteers (11.6 +/- 3.7 years; 6 female, 6 male) and 14
      unmedicated children with SAD (11.0 +/- 3.3 years; 9 female, 5 male) meeting
      Rosenthal/NIMH criteria for SAD and Schedule for Affective Disorders and
      Schizophrenia for School-Age Children-Epidemiologic version criteria for major
      depression had their levels of activity recorded for 72 hours (weekdays) using
      belt-worn actigraphs. RESULTS: The SAD group had blunted circadian amplitudes
      that were 10% lower than normal (p = .004). They were more poorly modeled by the
      standard cosinor equation (p = .001), and a circadian rhythm accounted for 39%
      less of the variability in their activity profile (p = .007). The amplitude of
      the 12-hour harmonic rhythm was markedly increased. There were no differences
      between SAD and control children in the timing of the circadian rhythm and degree
      of entrainment. CONCLUSIONS: Children with SAD displayed dysregulated circadian
      activity rhythms comparable with those reported in nonseasonally depressed
      children, yet different from those observed in adults.

PMID- 9031572
TI  - Examination of children's responses to two preventive intervention strategies
      over time.
AB  - OBJECTIVE: To examine long-term effects of two forms of preventive intervention
      designed to increase families' understanding of parental affective disorder and
      to prevent depression in children. METHOD: Thirty-six families who had a
      nondepressed child between ages 8 and 15 years and a parent who had experienced
      affective disorder were enrolled and randomly assigned to either a clinician
      facilitated intervention or a lecture discussion group. Each parent and child
      were assessed prior to randomization, after intervention, and approximately 1 1/2
      years after enrollment. Assessments included standard diagnostic interviews,
      measures of child and family functioning, and interviews about experience of
      parental affective disorder and intervention effects. RESULTS: Children in the
      clinician-facilitated group reported greater understanding of parental affective
      disorder, as rated by self-report, rater-generated scales, and parent report, and
      had better adaptive functioning after intervention. Parents in the clinician
      facilitated intervention group reported significantly more change. CONCLUSION:
      Findings from both interventions support the value of a future-oriented
      resiliency-based approach. The greater effects of the clinician-facilitated
      intervention support the need for linking cognitive information to families' life
      experience and involving children directly in order to achieve long-term effects.

PMID- 9031573
TI  - Associations between expressed emotion and child behavioral inhibition and
      psychopathology: a pilot study.
AB  - OBJECTIVE: To examine the relationship between behavioral inhibition and child
      psychopathology and measures of family adversity indexed through "expressed
      emotion." METHOD: Maternal expressed emotion was assessed via Five-Minute-Speech
      Sample in two samples of children evaluated for prevalence of DSM-III disorders
      and assessed via laboratory observations for behavioral inhibition. The at-risk
      sample (N = 30) consisted of 4- to 10-year-old children of mothers with and
      without panic disorder (psychiatric controls). The Kagan sample (N = 41)
      consisted of children selected at age 21 months as behaviorally inhibited or
      uninhibited and followed through age 11. RESULTS: In the at-risk sample, child
      behavioral inhibition was associated with high/borderline maternal criticism,
      independent of other measures of child psychopathology. In both samples combined,
      high/borderline maternal criticism was associated with child externalizing
      symptoms and with the number of child mood and behavior disorders. Emotional
      overinvolvement was significantly associated with child separation anxiety
      disorder in the at-risk sample. CONCLUSIONS: Results suggest that child
      behavioral inhibition may be associated with maternal criticism/dissatisfaction
      and confirm other reports of associations between criticism and child behavior
      and mood disorders and between emotional overinvolvement and child separation
      anxiety.

PMID- 9031574
TI  - Panic disorder and agoraphobia in consecutively referred children and
      adolescents.
AB  - OBJECTIVE: This report examines the clinical features and correlates of juvenile
      panic disorder in referred children and adolescents to test specific hypotheses
      about its relationship with adult panic disorder. METHOD: The sample consisted of
      consecutively referred children and adolescents (N = 472) comprehensively
      evaluated with structured diagnostic interviews, cognitive tests, and
      psychosocial assessments. RESULTS: Panic disorder was identified in 6% and
      agoraphobia in 15% of psychiatrically referred children and adolescents. Children
      meeting criteria for panic disorder also frequently met criteria for agoraphobia.
      The latter disorder was more prevalent and had an earlier age at onset than panic
      disorder. Children with panic disorder and those with agoraphobia had similar
      correlates with frequent comorbidity with other anxiety and mood disorders. A
      high level of comorbidity with disruptive disorders was also identified.
      CONCLUSIONS: These results support the hypothesis of continuity between the
      juvenile and the adult form of panic disorder. However, the high level of
      comorbidity with disruptive behavior disorders also suggests developmentally
      specific discontinuities between juveniles and adults with panic disorder.

PMID- 9031575
TI  - Mental health problems of children of migrant and seasonal farm workers: a pilot
      study.
AB  - OBJECTIVE: Children of migrant and seasonal farm workers constitute important
      populations for study because they chronically experience extreme poverty and
      parental unemployment. Also, migrant children are exposed to chronic residential
      and school mobility. METHOD: Mothers and children were interviewed using the
      Diagnostic Interview Schedule for Children Version 2.1. RESULTS: The results
      indicated that 66% of the children had one or more psychiatric diagnoses based on
      mother or child reports, with anxiety disorders being the most prevalent
      diagnosis. CONCLUSIONS: These findings suggest the need for a larger,
      epidemiological study of the psychiatric morbidity of rural children of farm
      workers.

PMID- 9031576
TI  - Psychopathy and conduct problems in children: II. Implications for subtyping
      children with conduct problems.
AB  - OBJECTIVE: To test whether the presence of callous and unemotional (CU) traits
      designates a unique subgroup of children with conduct problems that corresponds
      more closely to adult conceptualizations of psychopathy. METHOD: A clinic
      referred sample of 120 children between the ages of 6 and 13 years were assessed
      using parent and teacher ratings of CU traits, as well as parent and teacher
      report on a structured interview assessing oppositional defiant disorder (ODD)
      and conduct disorder (CD) symptoms. RESULTS: A cluster analysis of the ratings of
      CU traits and ODD/ CD symptoms revealed four clusters of children, two of which
      had high rates of ODD and CD symptoms. One of these conduct problem clusters also
      exhibited high levels of CU traits (n = 11). These children had a greater number
      and variety of conduct problems, a stronger history of police contacts, and a
      stronger parental history of antisocial personality disorder, despite being of
      higher intelligence than other children with significant conduct problems (n =
      29). CONCLUSION: The presence of CU traits with significant conduct problems
      seems to designate a unique subgroup of antisocial children who show a very
      severe pattern of antisocial behavior and who correspond more closely to adult
      conceptualizations of psychopathy.

PMID- 9031577
TI  - Nonpharmacological response in hospitalized children with conduct disorder.
AB  - OBJECTIVE: There is a paucity of research regarding the effects of
      hospitalization and/or the response to placebo in children with conduct disorder
      who are hospitalized for chronic and severe aggression. However, many children
      with this problem are hospitalized and immediately begin pharmacotherapy. In this
      report, the effects of hospitalization and placebo administration were examined.
      METHOD: Subjects were forty-four children (37 males, 7 females) with conduct
      disorder, aged 9.83 to 17.14 years, who were hospitalized for chronic and severe
      aggression. This was a 4-week double-blind and placebo-controlled study with a 2
      week single-blind placebo lead-in period. During the 2-week placebo baseline
      period, aggression was measured on a 24-hour basis, using the Overt Aggression
      Scale. Only subjects meeting a specific aggression criterion were randomized to
      the treatment period of the trial. RESULTS: Of the 44 subjects enrolled, 23
      (52.3%) met the aggression criteria for entering the treatment period (baseline
      nonresponders), while 21 (47.7%) did not (baseline responders). Thus, almost half
      of the subjects, while taking no active medication, benefited from the inpatient
      milieu/structure and/or placebo. CONCLUSION: This finding has important treatment
      and research implications. Medication to treat aggression should not be initiated
      immediately upon hospitalization because improvements associated with
      hospitalization may be attributed inaccurately to pharmacotherapy, resulting in
      unnecessarily medicating children. A placebo baseline period is essential to
      decrease the risk of a type II error in pharmacological research concerning
      aggression.

PMID- 9031578
TI  - Combined pharmacotherapy in children and adolescents in a residential treatment
      center.
AB  - OBJECTIVE: To investigate characteristics of children and adolescents with a
      history of combined pharmacotherapy (CPT) and compare them with a group with no
      history of CPT. METHOD: Eighty-three consecutive admissions to a residential
      treatment center were divided into a CPT and a no-CPT group based on treatment
      history and compared by chart review. Prevalence of lifetime psychiatric
      medication use and CPT exposure were assessed. Demographic, diagnostic,
      treatment, behavioral, and medication variables were compared across the two
      groups. RESULTS: Medication use was present in the treatment history for 89.2%
      and a history of CPT was found for 60.3% of subjects. Admission to current
      placement from inpatient psychiatry, lifetime number of psychiatric placements,
      lifetime number of psychiatric diagnoses, and nonseizure neuropsychiatric
      comorbidity were significantly associated with CPT. Aggression and neuroleptic
      use were also significantly associated with CPT. Admission psychiatric diagnostic
      comorbidity was not associated with CPT. CONCLUSIONS: A high prevalence of
      psychiatric medication use and CPT was found in this population. Variables
      assessing illness severity, aggressive behavior, and nonseizure neuropsychiatric
      comorbidity may identify youths in psychiatric treatment settings with a high
      prevalence of past or current CPT exposure. Further research on the CPT of
      aggression is warranted.

PMID- 9031579
TI  - Psychiatric risk associated with early puberty in adolescent girls.
AB  - OBJECTIVE: This study prospectively evaluated the relationship between early
      puberty and the onset of internalizing symptoms and disorders in adolescent
      girls. METHOD: The sample was drawn from 1,463 sixth-, seventh-, and eighth-grade
      girls who participated in a longitudinal school-based study of growth and
      development. Pubertal stage was determined by self-assessment of Tanner stage.
      Psychiatric assessments included self-report instruments and structured
      diagnostic interviews. Survival methods were utilized for data analysis. RESULTS:
      Girls with onset of internalizing symptoms were on average 5 months earlier in
      pubertal development than those who were asymptomatic (p < .001). In addition,
      girls with earlier maturation (earliest quartile) were more likely to develop
      internalizing symptoms than were nonearly matures (hazard ratio = 1.8, confidence
      interval = 1.2, 2.7). In a subsample of girls followed into high school, early
      maturing girls were at marginally higher risk (p < .10) for developing
      internalizing disorders by the study's end. The highest risk for internalizing
      disorders was for those girls with both early puberty and prior internalizing
      symptoms (odds ratio = 3.3). CONCLUSION: Early puberty increases the risk of
      internalizing symptoms and perhaps internalizing disorders in adolescent girls.

PMID- 9031580
TI  - Sex reassignment of adolescent transsexuals: a follow-up study.
AB  - OBJECTIVE: To investigate postoperative functioning of the first 22 consecutive
      adolescent transsexual patients of our gender clinic who underwent sex
      reassignment surgery. METHOD: The subjects were interviewed by an independent
      psychologist and filled out a test battery containing questionnaires on their
      psychological, social, and sexual functioning. All subjects had undergone surgery
      no less than 1 year before the study took place. Twelve subjects had started
      hormone treatment between 16 and 18 years of age. The posttreatment data of each
      patient were compared with his or her own pretreatment data. RESULTS:
      Postoperatively the group was no longer gender-dysphoric; they scored in the
      normal range with respect to a number of different psychological measures and
      they were socially functioning quite well. Not a single subject expressed
      feelings of regret concerning the decision to undergo sex reassignment.
      CONCLUSIONS: Starting the sex reassignment procedure before adulthood results in
      favorable postoperative functioning, provided that careful diagnosis takes place
      in a specialized gender team and that the criteria for starting the procedure
      early are stringent.

PMID- 9031581
TI  - Obstetric complications in autism: consequences or causes of the condition?
AB  - OBJECTIVE: To determine whether and why obstetric complications are associated
      with autism. METHOD: Obstetric histories, obtained at maternal interview and
      coded as an optimality score (OS), were compared in two groups: 78 families
      containing an autistic proband (ICD-10 criteria) and 27 families containing a
      down syndrome (DS) proband. The OS was examined in relation to offspring
      diagnosis, proband characteristics, and familial loading for autism and its
      phenotypic variants. RESULTS: Autistic and DS probands had a significantly
      elevated OS compared with unaffected siblings, regardless of birth order
      position. The elevation was mainly due to an increase in mild as opposed to
      severe obstetric adversities. In autistic probands, the OS was best predicted by
      familial loading for autism and its phenotypic variants, but in the absence of
      this measure by the number of autistic symptoms. Among siblings of autistic
      probands affected with autism or its variants, the OS was best predicted by the
      probands' OS, and in its absence, by the measure of familial loading. In DS
      probands and siblings the OS was associated with increased maternal age, although
      this did not account for the OS elevation in DS probands. CONCLUSIONS: Rather
      than playing any principal etiological role, the obstetric adversities associated
      with autism either represent an epiphenomenon of the condition or derive from
      some shared risk factor(s).

PMID- 9031582
TI  - Macrocephaly in children and adults with autism.
AB  - OBJECTIVE: To explore the frequency and onset of macrocephaly in autism and its
      relationship to clinical features. METHOD: Head circumferences at birth, during
      early childhood, and at the time of examination were studied in a community-based
      sample of autistic children and adults. The authors investigated whether head
      circumference at the time of examination was associated with clinical features.
      RESULTS: Fourteen percent of the autistic subjects had macrocephaly: 11% of males
      and 24% of females. In most, the macrocephaly was not present at birth; in some
      it became apparent in early and middle childhood as a result of increased rate of
      head growth. A small relationship was noted between head circumference percentile
      and less severe core features of autism. Neither macrocephaly nor head
      circumference percentile was associated with nonverbal IQ, verbal status, seizure
      disorder, neurological soft signs or minor physical anomalies in the autistic
      subjects. CONCLUSION: Macrocephaly is common in autism and usually is not present
      at birth. Rates of head growth may be abnormal in early and middle childhood in
      some (37%) children with autism. Macrocephaly does not define a homogeneous
      subgroup of autistic individuals according to clinical features.

PMID- 9031583
TI  - The clinical assessment of attachment in children under five.

PMID- 9031584
TI  - Longitudinal Doppler study of fetal haemodynamic parameters throughout pregnancy:
      preliminary results.

PMID- 9031585
TI  - [A quantitative analysis of regional left ventricular myocardial function by
      pulsed tissue Doppler in coronary disease. A new index of regional left
      ventricular diastolic dysfunction].

PMID- 9031587
TI  - Recommendations of the European Board for the Specialty Cardiology (EBSC) for
      education and training in basic cardiology in Europe. The Executive Committee of
      the European Board for the Specialty Cardiology.
AB  - The Cardiology Monosection of the UEMS and the European Society of Cardiology
      have created a European Board for the Specialty of Cardiology whose task is to
      prove guidelines for training and training institutions. The recommendations are
      presented here and in summary require at least 3 years education and training in
      basic cardiology (after at least 2 years of a common trunk of general internal
      medicine) at an approved institution with adequate exposure to all aspects of
      adult cardiological practice.

PMID- 9031588
TI  - Immunochemical localization of chromaffin cells during the embryogenic migration.
AB  - Adrenal medulla together with the sympathetic nervous system constitute an
      anatomo functional unit. Both tissues derive from precursor cells which originate
      from the neural crest and later differentiate during migration into sympathetic
      neurons or chromaffin cells. Biosynthesis enzymes of catecholamines such as DBH
      (dopamine beta hydroxylase) and PNMT (phenylethanol amine-N-methyl transferase)
      as well as the neurotransmitter serotonin , can be detected by
      immunohistochemical techniques from 15 to 20 prenatal days. Cells migrating along
      the dorsal aorta could be observed at 15 prenatal days. From day 16 on, three
      distinct cellular groups could be distinguished according to the intensity of the
      immunoreactivity: chromaffin, paraganglion and sympathetic ganglion cells. From
      day 18, chromaffin cells immunostained as DBH' PNMT+ or DBH+ PNMT could be
      detected differentiating into what would be adrenergic or noradrenergic cells,
      respectively Progenitor cells migrating from the neural crest to the adrenal
      cortical blastema reach a micro-environment where glucocorticoids could possibly
      influence gene expression for PNMT in some of these undifferentiated cells,
      causing adrenaline synthesis. Serotonin(5HT) immunoreactivity is localized from
      17 prenatal days in several groups of the paraganglionic cells where they could
      be a modulator for chromaffin differentiation.

PMID- 9031589
TI  - Variability in the cell phenotype of aggregates or "clones" of human
      osteoarthritic cartilage. A case report.
AB  - Human samples of articular cartilage from the knee of a clinically classified
      osteoarthritic patient, assessed by arthroscopy as part of the surgical treatment
      was studied by light and transmission electron microscopy. This particular case
      differed from others already reported in the variability of cell phenotype within
      the aggregates or "clones" frequently present in the osteoarthritic cartilage.
      The most common morphology of "clonal" cells forming the aggregates were large
      and rounded with an euchromatic nucleus. The cytoplasm was characterized by the
      presence of alternately clear and dense sites. At the ultrastructural level it
      was seen that the clear sites were formed by disrupted intermediates filaments
      and small particles, and that the dense sites were constituted by the segregation
      of different organelles of the chondrocytes. In addition, there were atypical
      aggregates composed only by secretory cells or by degenerating chondrocytes.
      Furthermore, a complex structure consisting of a very large cell inside a giant
      lacunae delimited by electron-dense material with small vesicles is described as
      a novel finding. The variability in the chondrocyte phenotype of the aggregates
      described here could be an indication of a better prognosis; nevertheless, the
      follow-up of the evolution of this patient is needed in order to know the final
      outcome.

PMID- 9031591
TI  - Double replicas allow the obtention of longitudinally freeze-fractured
      Trypanosoma cruzi.
AB  - The double replica device was used to obtain freeze-fracture replicas of gently
      pressed cells, allowing the visualization of a large number of longitudinally
      fractured epimastigote and trypomastigote forms of Trypanosoma cruzi. This
      technique revealed large areas of the plasma membrane, the region of attachment
      of the flagellum to the cell body and the branched mitochondria.

PMID- 9031590
TI  - Protective immunity induced by a Yersinia enterocolitica serovar 0:8 cellular
      extract.
AB  - The purpose of this study was to investigate the protective power of a cellular
      extract (CE) from Y. enterocolitica 0:8 grown in condition of expression of
      chromosomal antigens. Mice were immunized by s.c. route and challenged with: 0
      LD50 (1 x 10(4) CFU/ml). Immunoblotting showed that CE-specific serum reacted
      with several CE antigens. Prominent bands, of molecular weights 60 and 35.5, were
      present in cytoplasmic and membrane fraction, respectively. The
      lipopolysaccharide (LPS) was detected in CE. These findings suggest that
      chromosomally-encoded antigens present in CE may induce protection against Y.
      enterocolitica infection. Both humoral and cellular immune response contribute to
      protection in mice.

PMID- 9031592
TI  - Nucleolar organizer regions in a model of cell hyperactivity and regression.
AB  - Nucleolar organizer regions stained with colloidal silver techniques (AgNOR)
      evidence sites of active rRNA transcription. It has been proved that AgNOR
      undergo a rise in number and variations in size and shape in conditions which
      traditionally involve enhanced cell proliferation and rRNA transcription. AgNOR
      have been described as a marker of malignant transformation in multiple entities.
      Our laboratory has previously described their value as markers of radioinduced
      damage. The finding, at light microscopy level, that silver staining persisted at
      later post-irradiation times when cells are characteristically inactive, prompted
      the present study to correlate findings at light microscopy level with the
      ultrastructural analysis of nucleoli and their AgNOR in a model of irradiated
      skin. We herein attempt to explain the biological significance of AgNOR
      variations in the different phases of radioinduced response (which involves
      cellular hyperactivity followed by regressive features). Ten Wistar rats were
      submitted to local irradiation of the left leg (the shielded right leg was used
      as control) with 50 Gy x rays and killed 15 days post- irradiation. Silver
      staining was performed on ultrathin sections. In the basal layer of control
      epithelium silver affinity was established for fibrillar centers (FC) and
      fibrillar dense components (DFC). During the phase of radioinduced hyperplasia (1
      3 days post-exposure) basal cells exhibit large reticular nucleoli, with
      irregular contours and silver staining on DFC. In the regressive phase (4-5 days
      post-irradiation) silver staining persists despite the halt in transcriptional
      activity, associated to homogeneous and compact nucleoli. These findings suggest
      caution in the interpretation of silver staining patterns.

PMID- 9031594
TI  - Vesicular transport in mammalian cells: techniques for in vivo regulation and in
      vitro reconstitution. Proceedings of a workshop. Mendoza, Argentina, April 15-25,
      1996.

PMID- 9031593
TI  - Standardization of fixation, processing and staining methods for the central
      nervous system of vertebrates.
AB  - This paper reports the standardization of methods used for processing and
      embedding various vertebrate brains of different size in paraffin. Other
      technical details developed for avoiding frequent difficulties arising during
      laboratory routine are also reported. Some modifications of the Nissl and Kluver
      Barrera staining methods are proposed. These modifications include: 1) a Nissl
      stain solution with a rapid and efficient action with easier differentiation; 2)
      the use of a cheap microwave oven for the Kluver-Barrera stain. These procedures
      have the advantage of permitting Nissl and Kluver-Barrera staining of nervous
      tissue in about five and fifteen minutes respectively. The proposed procedures
      have been tested in brains obtained from fish, amphibians, reptiles and mammals
      of different body sizes. They are the result of our long experience in preparing
      slides for comparative studies. Serial sections of excellent quality were
      regularly obtained in all the specimens studied. These standardized methods,
      being simple and quick, are recommended for routine use in neurobiological
      laboratories.

PMID- 9031595
TI  - Compartmental organization of ganglioside synthesis in the Golgi complex.

PMID- 9031596
TI  - Mechanism of formation of post Golgi vesicles from TGN membranes: Arf-dependent
      coat assembly and PKC-regulated vesicle scission.
AB  - We have developed an experimental system that utilizes purified Golgi fractions
      obtained from virus infected infected MDCK cells to reproduce in vitro the
      process of vesicle generation in the trans Golgi network, an important site for
      the sorting of proteins addressed to the plasma membrane, secretory vesicles, or
      lysosomes. Using an integrated biochemical and electron microscopic approach, we
      have shown that the formation of post Golgi vesicles carrying proteins destined
      to both plasma membrane domains of epithelial cells requires the activation of an
      ArF-like GTP-binding protein that serves to promote the assembly of the protein
      coat necessary to deform the donor membrane and generate a vesicle. The formation
      of the post Golgi vesicles also requires the participation of a Golgi membrane
      associated Protein Kinase C, but not its phosphorylating activity. Other authors
      have shown that this is also the case for the PKC activation of the enzyme
      phospholipase D, which generates phosphatidic acid from phosphatidyl choline and
      may be involved in remodeling of membranes. We have been able to dissect the
      process of post Golgi vesicle generation into two sequential stages, one of coat
      assembly and bud formation, and a subsequent one of vesicle scission. The first
      stage can occur at 20 degrees C and requires the activation of the Arf protein
      necessary for coat assembly. The second stage does not require nucleotides or an
      energy supply, but requires cytosolic proteins, and in particular, an NEM
      sensitive membrane scission promoting activity that operates only at a higher
      temperature of incubation. Because various PKC inhibitors blocked vesicle
      scission without preventing bud formation, we propose that the PKC is required
      for the activation of a PLD in the TGN, which leads to remodeling of the donor
      membrane and the severing of connections between the emerging vesicles and the
      membranes.

PMID- 9031597
TI  - The adaptor complexes: a bridge between the transmembrane proteins and clathrin
      lattices.

PMID- 9031598
TI  - Let's think about coat proteins.

PMID- 9031599
TI  - Factors regulating organelles transport along microtubules.

PMID- 9031600
TI  - Role for NSF on vesicular transport: insights from in vitro endosome fusion.

PMID- 9031601
TI  - Rab5 GTPase and endocytosis.

PMID- 9031602
TI  - Rab5 regulates the dynamics of early endosome fusion.

PMID- 9031603
TI  - Calcium- and zinc-binding proteins in intracellular transport.
AB  - The complex mechanism of intracellular transport is regulated by free calcium in
      different manners. Calcium binding proteins regulate several aspects of the
      vesicle fusion mechanism mediated by NSF (N-ethylmaleimide sensitive fusion
      factor). At least in some regulated exocytosis, calcium-binding proteins are the
      trigger for fusion downstream of NSF, Still, calcium-binding proteins, such as
      annexins, may be part of a different fusion mechanism mediating some specific
      transport steps or working in parallel to the NSF-dependent fusion process.
      Calcium is not the only ion necessary for the function of factors involved in
      vesicular transport. A zinc requirement has been also proposed. One of the zinc
      dependent factors is probably a protein with a cysteine-rich region that
      coordinates zinc and binds phorbol esters. Although protein kinase C is the more
      prominent family of proteins carrying this domain, the factor necessary for
      transport does not appear to function as a kinase.

PMID- 9031604
TI  - Vesicular transport: implications for cell polarity.
AB  - In polarized cells intracellular sorting of plasma membrane proteins occurs to a
      large extent at the trans-Golgi network, giving rise to vesicles destined for
      distinct plasma membrane domains. This review discusses the several pathways,
      both direct and indirect, which lead to protein incorporation into the correct
      cell surface, as well as the mechanisms involved. Proteins contain signals which
      direct their incorporation into the distinct vesicles destined for plasma
      membrane microdomains. Specific coat proteins are involved in vesicle assembly
      and are likely to play a role in the generation of discrete vesicle populations.
      Molecules involved in vesicle docking and fusion may also add specificity to the
      targeting process.

PMID- 9031605
TI  - Vesicular transport of microorganisms in macrophages.

PMID- 9031606
TI  - International Anesthesia Research Society 71st Clinical and Scientific Congress.
      San francisco, California, March 14-18, 1997. Abstracts.

PMID- 9031607
TI  - Association of natural killer cell immune recovery with a graft-versus-leukemia
      effect independent of graft-versus-host disease following allogeneic bone marrow
      transplantation.
AB  - There is good evidence that T lymphocytes play an important role in the graft
      versus-leukemia (GVL) effect following allogeneic bone marrow transplantation
      (BMT) for hematologic malignancies. However, the role of natural killer (NK)
      cells in GVL is less clear. To further investigate a possible association of NK
      cells with GVL we studied 15 patients undergoing BMT for chronic myeloid leukemia
      (CML), correlating T-cell (CD4+ and CD8+) and NK-cell (CD16+ 56+) recovery with
      relapse and graft-versus-host disease (GVHD). Patients were studied on three
      occasions up to 9 months after BMT, for lymphocyte surface phenotype and for
      spontaneous and IL-2-stimulated (LAK cell) cytotoxic function. Circulating CD8+
      and NK but not CD4+ cell numbers were significantly lower in five patients who
      relapsed compared with those remaining in remission after BMT (mean 0.03 vs 0.32
      x 10(9)/l, p = 0.002 for CD8+ cells: mean 0.03 vs 0.11 x 10(9)/l, p = 0.002 for
      NK cells). There was no correlation of CD4+. CD8+, or NK cell numbers and
      development of grade-II or more acute GVHD. Spontaneous NK cytotoxic function
      rose to within the normal range in the first month after BMT. LAK function
      remained low during the study period. These results link NK cell recovery more
      closely with a GVL than with a GVH effect.

PMID- 9031608
TI  - First-line treatment of Waldenstrom's disease with cladribine.
      Arbeitsgemeinschaft Medikamentose Tumortherapie.
AB  - PURPOSE: To assess the activity and side effects of cladribine (2-CdA) treatment
      in patients with advanced Waldenstrom's disease. PATIENTS AND METHODS: Ten
      symptomatic patients without prior therapy were included in a prospective
      multicenter trial. 2-CdA was administered daily at 0.12 mg/kg body weight in a 2
      h i.v. infusion over 5 consecutive days: this was repeated every 28 days for four
      cycles. Patients achieving a remission received interferon alfa-2c (1F) 15
      micrograms s.c. three times a week for 1 year. RESULTS: All 10 patients responded
      to 2-CdA (100%; 95% confidence interval, 68-100%), with one complete (CR) and
      eight partial responders (PR): one patient had only one 2-CdA cycle and showed a
      minor improvement (MR). Patients tolerated the treatment well. Despite
      considerable immunosuppression, an infection occurred in only two patients. After
      a median observation period of 57 weeks, three patients had shown progression,
      including one who died of lymphoma. CONCLUSION: 2-CdA induction and IF
      maintenance is a well-tolerated therapy for symptomatic untreated patients with
      advanced Waldenstrom's disease and offers excellent palliation.

PMID- 9031609
TI  - Codon 12 ras mutations in patients with myelodysplastic syndrome: incidence and
      prognostic value.
AB  - To determine the prevalence of activated rasoncogenes (N-ras, Harvey-ras Kirsten
      ras), DNA derived from peripheral blood of 51 patients with myelodysplastic
      syndrome (MDS) was investigated. The method was based on the polymerase chain
      reaction (PCR) technique to amplify DNA, followed by restriction fragment length
      polymorphism (RFLP) analysis. Among the French-American-British (FAB) subtypes, N
      ras mutations were found in two patients with refractory anemia with excess of
      blasts (RAEB), in one patient with refractory anemia with excess of blasts in
      transformation (RAEB-t), and in two patients with chronic myelomonocytic leukemia
      (CMML). MDS patients with a mutation at codon 12 of the N-ras gene showed shorter
      survival duration than other MDS patients of the same FAB subtypes, although
      these findings proved to be not statistically significant (P > 0.1).
      Interestingly, all but one patient with N-ras mutation developed acute
      myelogenous leukemia (AML). In conclusion, the presence of mutation at codon 12
      of the N-ras gene might serve as a negative prognostic factor at diagnosis of
      MDS.

PMID- 9031610
TI  - Inhibition of monocyte and polymorphonuclear granulocyte immune phagocytosis by
      monoclonal antibodies specific for Fc gamma RI, II and III.
AB  - We tested two Fc gamma receptor I (Fc gamma RI); six Fc gamma RII; and six Fc
      gamma RIII-specific monoclonal antibodies (mAb) for their capacity to inhibit
      monocyte and polymorphonuclear granulocyte (PMN) immune phagocytosis which is
      mediated by Fc gamma R. We used human red blood cells (rbc) coated with hIgG1 or
      mIgG1 as Fc gamma RI- and Fc gamma RII-specific target cells, respectively. The
      Fc gamma RI-specific mAbs 22.2 and 32.2 did not inhibit Fc gamma RI- or Fc gamma
      RII-specific monocyte immune phagocytosis. The Fc gamma RII-specific mAbs IV.3,
      CIKM5, FLI8.2, FLI 8.26, 2E1, and 41H16 inhibited Fc gamma RII-specific monocyte
      immune phagocytosis in all Fc gamma RIIa high-responder (HR) individuals but did
      not inhibit Fc gamma RI-specific phagocytosis. Using PMN, FL18.2 and 2E1 only
      partially inhibited phagocytosis in HR individuals, but the Fc gamma RIII
      specific mAbs 3G8, DJ130c. MFM-154. B88-9 and MG38 completely inhibited Fc gamma
      RII-specific phagocytosis if the corresponding antigen was available on the cell
      surface. In these cases phagocytosis inhibition may be explained by cross-linking
      of Fc gamma RII and Fc gamma RIII via one antibody molecule, with the Fab portion
      binding to Fc gamma RIII and the Fc portion binding to Fc gamma RII.

PMID- 9031612
TI  - Acute abdomen due to endometriosis as a diagnostic and therapeutic challenge in
      the treatment of acute myelocytic leukemia.
AB  - Acute abdominal pain is a frequent diagnostic and therapeutic challenge in
      hematologic patients. We report on the very rare case of organ endometriosis with
      acute abdominal symptoms in a 43-year-old female patient with AML-M5, starting 4
      days after induction chemotherapy with idarubicin, ara-C, and etoposide. The
      patient presented with an acute abdomen with clinical findings of acute
      cholecystitis, subileus, and local pain in the right upper abdomen accompanied by
      severe diarrhea. Probably due to impaired intestinal resorption, menstrual
      bleeding occurred despite regular administration of lynestrenol. Ultrasound
      examination of the abdomen disclosed a tumor with poor echoes in the pouch of
      Douglas, a subcapsular splenic hemorrhage, and a thickened gallbladder wall with
      surrounding edema. A cystic adnex tumor was confirmed by endovaginal ultrasound.
      Based on history and the findings on ultrasound, an endometriosis was diagnosed,
      and the LHRH agonist (nafarelin) was administered nasally in combination with
      lynestrenol. Following this medication the abdominal pain ceased, supporting the
      diagnosis of endometriosis. Nasal administration of an LHRH agonist in the
      following cycles of chemotherapy was effective in preventing further abdominal
      discomfort and vaginal bleeding. LHRH agonists should be given to patients with
      known endometriosis before starting myeloablative chemotherapy to prevent painful
      hemorrhage from endometriosis.

PMID- 9031613
TI  - Spontaneous splenic rupture in two patients with a blastoid variant of mantle
      cell lymphoma.
AB  - Spontaneous rupture of the spleen is a rare complication of hematological
      malignancies, occurring most commonly in patients with acute leukemia, but it has
      been documented in chronic leukemias and also in lymphomas. We report two
      patients with histologically and immunohistochemically confirmed mantle cell
      lymphoma (MCL) who experienced a spontaneous splenic rupture. An 80-year-old
      woman and a 51-year-old man had a blastoid variant of MCL and responded poorly to
      conventional treatment. Both patients recovered after splenectomy. The woman died
      of progressive lymphoma 2 months later. An allogeneic bone marrow transplantation
      was performed in the man with a good initial result, but an aggressive relapse
      was seen only 6 months later and he died of progressive lymphoma. In view of our
      data, we suggest special caution when MCL is complicated by rapid progression and
      severe splenomegaly. Although it is a rare phenomenon, the risk of splenic
      rupture should be kept in mind.

PMID- 9031611
TI  - Epstein-Barr virus-associated persistent polyclonal B-cell lymphocytosis with a
      distinct 69-base pair deletion in the LMP1 oncogene.
AB  - Epstein-Barr virus (EBV) genomes have been detected in peripheral blood
      lymphocytes (PBL) of patients with persistent polyclonal B-cell lymphocytosis
      (PPBL). This is consistent with the hypothesis that latent EBV infection is
      involved in the pathogenesis of this disorder. Two EBV-encoded proteins expressed
      in viral latency are the latent membrane proteins 1 and 2A (LMP1 and LMP2A). We
      have studied the LMP1 oncogene and the LMP2A gene in a female patient with PPBL
      and her five siblings. A cell line derived from peripheral blood lymphocytes
      (PBL) of the patient was also analyzed. A distinct 69-base pair deletion was
      identified within the carboxy terminal NF-kappa B activation domain of the LMP1
      oncogene in PBL of the patient and in the cell line, whereas none of the siblings
      harbored this deletion. The tyrosine-signaling motif and the HLA A2.1 epitope of
      the LMP2A gene were wild type in the patient and all siblings. The presence of a
      69-base pair deletion variant of the LMP1 oncogene within the lymphocytes of a
      PPBL patient but absence of this deletion variant in the unaffected siblings
      suggests a direct implication of altered LMP1 oncoprotein-dependent function in
      the pathogenesis of PPBL.

PMID- 9031614
TI  - Clonal CD5-positive B lymphocytes in myelodysplastic syndrome with systemic
      vasculitis and trisomy 8.
AB  - Bone marrow and peripheral blood from a myelodysplastic syndrome (MDS) patient
      with trisomy 8 and associated systemic vasculitis was investigated for clonal
      lymphoid lineage involvement using simultaneous metaphase and interphase
      fluorescence in situ hybridization (FISH) and immunocytochemistry with antibodies
      against CD13 (granulocytic), glycophorin A (GPA, erythroid), and the lymphocytic
      antigens CD3. CD5, CD20, and CD22. Trisomy 8 was detected in 55% of CD13+, 40% of
      GPA+, 6% of CD5+, and 5% of CD20/22+, but not in CD3+ cells. In a complementary
      experiment using interphase FISH on bone marrow cells sorted by flow cytometry,
      13% of CD5/CD19 double-positive cells (76% purity) were found to be trisomic. The
      results indicate the existence of a small CD5-positive B-lymphoid clone as part
      of the MDS process in this patient. Since CD5/19-positive cells have been
      proposed to be autoantibody producing, this finding might be a clue to the
      pathogenesis underlying the propensity for MDS patients to develop immune
      mediated complications.

PMID- 9031615
TI  - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): report
      of a patient with isolated renotesticular involvement after cure of non-Hodgkin's
      lymphoma.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML)-Rosai-Dorfman disease-is
      a rare but well-defined benign histiocytic proliferative disorder. We report an
      unusual patient, cured of non-Hodgkin's lymphoma, who presented 12 years later
      with renotesticular SHML associated with IgA monoclonal gammopathy, but without
      any evidence of relapsed lymphoma. The genitourinary manifestations of this
      disorder with massive lymphadenopathy and its rare association with malignant
      lymphoma are reviewed.

PMID- 9031616
TI  - Behcet's disease in patients with chronic myelogenous leukemia: possible role of
      interferon-alpha treatment in the occurrence of Behcet's symptoms.
AB  - Two patients with chronic myelogenous leukemia (CML) who developed characteristic
      features of Behcet's disease (BD) during alpha-interferon (IFN-alpha) treatment
      and another patient who had a diagnosis of BD preceding CML are presented. In the
      first two patients, features of BD appeared 6 months after the initiation of IFN
      alpha treatment: they included recurrent oral aphthae, genital ulceration,
      arthritis, folliculitis, and a positive skin pathergy test. The third patient,
      however, had a diagnosis of Behcet's disease 4 years before diagnosis of
      Philadelphia-positive CML. We prospectively examined the skin pathergy reaction
      in a group of patients with CML, multiple myeloma, and hairy cell leukemia both
      before and after IFN-alpha treatment and found two additional patients with CML
      who developed a positive skin pathergy test following IFN-alpha treatment.

PMID- 9031617
TI  - APC resistance as an additional thrombotic risk factor in a patient suffering
      from polycythemia vera and recurrent thrombosis.
AB  - Patients with polycythemia vera (PV) have a high risk of thrombosis. However,
      thrombosis is not sufficiently predictable with standard diagnostic procedures.
      We report on a patient with PV and recurrent thrombosis who nevertheless had a
      low platelet count while under therapy with hydroxyurea. As a result of duodenal
      ulcer and gastrointestinal bleeding, treatment with phenprocoumon was stopped
      years ago. Recently, heterozygosity for the factor V gene defect was diagnosed
      and anticoagulation therapy was reconsidered. In conclusion, the presence of
      resistance to activated protein C was an additional thrombotic risk factor that
      was important for our decision to change the treatment strategy in our patient.

PMID- 9031618
TI  - The pH value changes in the periodontal pockets.
AB  - Many studies have been done of the pH values in periodontal pockets. These
      studies have suggested that the pH value was influenced by the condition of the
      surrounding tissue. Thus, the measurement of pH in the periodontal pockets would
      be effective data to use for diagnosis in periodontal tissue. The sensors which
      have been used for measuring pH had many disadvantages, however, such as large
      size, slow response speed, instability in chemical substances, weak physical
      strength, thermal drift and so on. Therefore, there have been few reliable data
      on the pH values in periodontal pockets. We developed a new type of pH sensor,
      which was designed for use in the periodontal pocket. The sensor was made by D.C.
      reactive sputtering of iridium oxide on solid substances. This sensor was easy to
      miniaturize, had quick response speed, and was stable with respect to chemical
      interfere, physical shock, thermal changes, and low electrical resistance. It was
      used in the present study to measure the pH values in the periodontal pockets of
      16 subjects for 7-73 weeks. Our results showed that the pH values in the
      periodontal pockets differed among the measuring points and were changeable. The
      pattern of change was similar in the same subject. The pH value changed depending
      on tooth condition. The salivary pH showed no correlation with that in the
      periodontal pockets.

PMID- 9031619
TI  - Articles on AIDS in major Japanese newspapers.
AB  - People in general obtain knowledge about AIDS through the mass media. It is
      interesting to know how newspapers have dealt with AIDS in recent years, since
      newspapers are the most important mass media. The number of articles on AIDS from
      1981 to 1994 was investigated in three major Japanese newspapers (Asahi, Yomiuri,
      and Mainichi) which are distributed nationwide. The first article appeared in
      1982, and the number of articles gradually increased to a peak (total 785
      articles) in 1987 when the first Japanese female patient was reported. Then, the
      number of articles decreased to 116 in 1989. The number of articles on AIDS in
      newspapers was not correlated with the reported number of patients.

PMID- 9031620
TI  - Characterization of the H1.5 gene completes the set of human H1 subtype genes.
AB  - The H1 histone family in mammals contains at least seven subtypes. In the past we
      have isolated six of the seven genes encoding these isoforms. To complete the set
      of the human H1 histone genes, we have designed two PCR primers deduced from a
      partially published sequence of the remaining histone H1 gene [Carozzi et al.
      (1984) Science 224, 1115-1118] and from a consensus sequence which we have
      derived from the conserved region of human histone H1 genes. Using these primers
      we have amplified a 417-bp DNA fragment from total human DNA. This fragment was
      used for screening a human phage genomic library. Two overlapping clones were
      isolated. The region contains a set of 5 genes representing each of the five
      histone classes. In continuation of our numbering of human H1 genes, we have
      named this H1 gene H1.5. This gene encodes a protein almost identical to the
      previously published protein sequence designated H1a [Ohe et al. (1986) J.
      Biochem. 100, 359-368]; since the changes are in a region of some uncertainty of
      the peptide sequencing, we conclude that the newly isolated gene codes for the
      H1a protein. The structures of the flanking regions of the genes except the H2B
      gene are typical for histone genes. They include: (1) a CCAAT element in the
      promotor region, (2) a TATA box and (3) a palindromic termination element. The
      H2B sequence shows no typical regulatory elements and no complete ORF, therefore
      we consider it as a pseudogene. The expression of the H1.5 gene was examined in
      several cell lines.

PMID- 9031621
TI  - Cloning and sequencing of the gene for a 120-kDa immunodominant protein of
      Ehrlichia chaffeensis.
AB  - Ehrlichia chaffeensis is the tick-borne, obligately intracellular bacterium that
      causes human monocytic ehrlichiosis. A 120-kDa protein is one of the
      immunodominant proteins of E. chaffeensis that stimulates production of specific
      antibodies in infected humans. A genomic library of E. chaffeensis was
      constructed in a lambda ZAP II phage vector, and a clone expressing the 120-kDa
      protein of E. chaffeensis was identified using canine anti-E. chaffeensis serum.
      DNA sequence analysis of the cloned 120-kDa protein gene of E. chaffeensis
      identified a 1884-bp open reading frame with an ehrlichial promoter. Five
      identical 240-bp tandem repeat units were identified in the 120-kDa protein gene
      of E. chaffeensis, comprising 60% of the entire gene. Aside from the first repeat
      unit, all the other repeat units are identical. In the first repeat unit there
      are four nucleotides that are different from the other repeats. Hydropathy
      analysis of the deduced amino-acid sequence demonstrated that the repeat domain
      contains highly hydrophilic segments. The 120-kDa protein should be evaluated for
      a role in stimulating protective immunity.

PMID- 9031622
TI  - Study of Alu sequences at the hypoxanthine phosphoribosyltransferase (hprt)
      encoding region of man.
AB  - The hypoxanthine phosphoribosyltransferase (hprt) encoding region of man is
      considered rich in Alu sequences: with 49 sequences present within 57 kilobases.
      Subfamily classification of the Alu sequences and identification of flanking
      direct repeats has been carried out to detect past rearrangements associated with
      their insertion into the region. Members of the Alu-J and three Alu-S subfamilies
      are present, along with the existence of free left arm sequences. Using available
      data, a comparison is made of the Alu subfamilies present at different gene
      regions. The heterogeneity in the number of each subfamily present at different
      genes shows that no one particular subfamily attained saturation in the genome.
      Several adjacent insertions of Alu sequences are seen at the hprt region.
      Furthermore two novel sequences are described, there is an incident where one Alu
      sequence has inserted into the middle poly(A) tract of an existing sequence at
      the hprt region; while another result from an Alu/Alu cross-over event elsewhere
      in the genome, before insertion into the hprt region. Once inserted, the Alu
      sequences are rarely subject to loss or rearrangement.

PMID- 9031624
TI  - Evolutionary conservation of putative functional domains in the human homolog of
      the murine His-1 gene.
AB  - The mouse His-1 gene encodes a spliced and polyadenylated RNA with no long open
      reading frame (ORF), making it difficult to distinguish a functional protein
      coding domain. To identify candidate protein coding ORFs, and other functionally
      significant regions, we have isolated and sequenced 8.5 kb of a human genomic DNA
      that is homologous to the mouse His-1 gene. Alignment of the mouse and human
      sequences required no extensive gapping, indicating that evolutionary constraints
      have maintained a requirement for colinearity in genomic organization. We have
      identified the mouse transcriptional start point (tsp) and shown that the
      sequence of the 5'-flanking region is highly conserved in the human homolog.
      Sequence comparisons between the mouse and human genes identified conservation of
      other putative functional domains in exon 3 and in each of the two introns.
      Southern blot analysis with probes from each of these regions detected homologs
      in multiple other vertebrate species. However, none of the multiple candidate
      ORFs in the mouse RNA were conserved in the human sequence, suggesting that the
      RNA is unlikely to encode a protein. These data suggest that the RNA may be the
      final and functional product from the mouse His-1 gene.

PMID- 9031623
TI  - Human inner ear OCP2 cDNA maps to 5q22-5q35.2 with related sequences on
      chromosomes 4p16.2-4p14, 5p13-5q22, 7pter-q22, 10 and 12p13-12qter.
AB  - Mouse Ocp2-rs2 maps to chromosome 11 and encodes an 18.6 kDa peptide abundantly
      expressed in the organ of Corti. We show that sequences similar to murine Ocp2
      rs2 are found on human chromosomes 4p16.2-4p14, 5p13-5q35.2, 7pter-q22, 10 and
      12p13-12qter as revealed by Southern blot analyses of human/rodent somatic cell
      hybrids. A fetal human inner ear cDNA library was screened with a cloned 254 bp
      PCR product of murine Ocp2-rs2. One of two human cDNA clones (CM1) was sequenced
      from the 5' end that begins with murine Ocp2-rs2 codon 14 through the stop codon
      and 258 nucleotides of 3-UTR and was found to have the identical deduced amino
      acid sequence to Ocp2-rs2. Based on the sequence in the 3'-UTR of CM1, a PCR
      primer pain was synthesized and used to confirm that a human homologue of Ocp2
      rs2, designated OCP2 and expressed in the developing human inner ear, is
      localized to 5q22-5q35.2. Other OCP2-like sequences located on chromosomes 4p16.2
      4p14, 7pter-q22 and 12p13-12qter (but not the chromosome 10 OCP2-like sequence)
      will PCR amplify the expected size product at a lower annealing temperature using
      the OCP2 3'-UTR PCR primers indicating that there may be a human OCP2 gene
      family.

PMID- 9031625
TI  - Cloning and characterization of Chinese hamster p53 cDNA.
AB  - We have cloned and sequenced Chinese hamster p53 cDNA and have compared the p53
      sequence in different Chinese hamster cell lines to several relevant phenotypes.
      Our results indicate that a mutation in CHO cells that changes Thr211 to Lys211
      abrogates the ability to arrest in G1 and apparently renders cells capable of
      amplifying DNA. However, this mutation has no effect on the G2 checkpoint or on
      acute down-regulation of DNA replication after a radiation challenge.

PMID- 9031626
TI  - Molecular analysis of the isocitrate lyase gene (acu-7) of the mushroom Coprinus
      cinereus.
AB  - The nucleotide sequence of the structural gene for isocitrate lyase (acu-7) is
      presented and features of its coding sequence and predicted protein are
      described. Several motifs were identified within the promoter region which are
      potentially involved in transcriptional regulation. Surprisingly, some of these
      occur within the coding sequence of an adjacent gene of unrelated function that
      terminates within 371 bp upstream from acu-7. The sequence of this second gene
      identified an N-acetylglucosamine-1-phosphate transferase.

PMID- 9031627
TI  - High-fidelity PCR amplification of infectious copies of the complete simian virus
      40 genome from plasmids and virus-infected cell lysates.
AB  - We describe here a long-polymerase chain reaction (PCR) method that can be used
      to amplify complete simian virus 40 (SV40) DNA with high fidelity, and we show
      that authentic, viable virus can be produced from molecular clones of the PCR
      amplified viral DNAs. A commercial long-PCR kit that employed a combination of
      Taq and GB-D polymerases was used, together with a pair of overlapping primers
      that recognized a unique EcoRI site in the SV40 genome. Efficient amplification
      required linearization of the circular SV40 genomic DNAs with EcoRI. Entire SV40
      genomes were successfully PCR-amplified from an SV40 plasmid and from two
      different SV40-infected cell lysates and were cloned into pUC-19. Three separate
      segments of the cloned viral genomes were DNA sequenced, and no nucleotide
      changes relative to the parental virus were detected, suggesting that the viral
      DNAs had been amplified with high fidelity. Each PCR clone was infectious, and no
      differences were detected in the growth characteristics of viruses derived from
      these clones as compared to the original viral strain. The procedure we utilized
      shortens and simplifies the molecular cloning of small double-stranded DNA
      viruses and will be useful for viral diagnostic tests and for recovery of virus
      from clinical samples. The results of these experiments have broad implications,
      as the methodology is applicable to many systems.

PMID- 9031628
TI  - Analysis of four tylosin biosynthetic genes from the tylLM region of the
      Streptomyces fradiae genome.
AB  - The tylLM region of the tylosin biosynthetic gene cluster of Streptomyces fradiae
      contains four open reading frames (orfs1*-4*). The function of the orf1* product
      is not known. The product of orf2* (tylM2) is the glycosyltransferase that adds
      mycaminose to the 5-hydroxyl group of tylactone, the polyketide aglycone of
      tylosin (Ty). A methyltransferase, responsible for 3-N-methylation during
      mycaminose production, is encoded by orf3* (tylM1). The product of orf4* (cer) is
      crotonyl-CoA reductase, which converts acetoacetyl-CoA to butyryl-CoA for use as
      a 4C extender unit during tylactone production.

PMID- 9031629
TI  - Rat and chicken s-rex/NSP mRNA: nucleotide sequence of main transcripts and
      expression of splice variants in rat tissues.
AB  - Two main transcripts of the s-rex/NSP gene are generated by different promoter
      usage and differential splicing in neuronal and endocrine tissues of higher
      vertebrates, suggesting that the encoded proteins function in neuroendocrine
      secretion. To know more about the structure, expression and evolution of this new
      gene, we have cloned full-length cDNAs for both 1.5 kb and 3.5 kb transcripts
      from rat and chicken brain cDNA libraries. Sequence analysis has revealed
      structures within the 3'-UTR that are conserved in these mRNAs and human NSP mRNA
      and that could be involved in specific compartmentalization of s-rex/NSP mRNA in
      neuronal cells. An additional transcript generated by differential splicing of
      internal exons has been cloned from a rat DRG library. Low levels of s-rex/NSP
      mRNAs have been detected in some non-neuroendocrine tissues, although substantial
      levels of a unique transcript have been found in rat tests. By RT-PCR analysis,
      other tissue-specific transcripts that are products of rare splicing events have
      been revealed.

PMID- 9031630
TI  - A novel satellite/microsatellite combination in the genome of the marine shrimp,
      Penaeus vannamei.
AB  - In our studies of repeated sequences in the genome of the marine shrimp, Penaeus
      vannamei (Pv), we have discovered a novel combination of sequence elements. We
      inserted restriction fragments of genomic DNA into a plasmid vector and screened
      for recombinant plasmids containing repeated sequences. Ten of the resulting
      isolates contained representatives of the same repeated element, a satellite
      sequence present in one or more blocks of tandemly repeated units. The cloned
      repeat units range in size from 139 to 188 bp. Embedded within each cloned repeat
      unit are 6-15 copies of a tandemly repeated pentanucleotide microsatellite. The
      genome of Pv contains approx. 1,000,000 copies of this satellite/microsatellite
      unit. Sequences that cross-hybridize strongly with this structure were found in
      the genomes of lobster and crayfish, but not in other species of the genus
      Penaeus.

PMID- 9031631
TI  - Characterization of a prion protein (PrP) gene from rabbit; a species with
      apparent resistance to infection by prions.
AB  - The prion protein gene (PrP) encodes a cellular protein of unknown function. A
      conformational isoform of this protein is involved in the neurodegenerative prion
      diseases. To facilitate the identification of structurally and antigenically
      important regions within the PrP molecule, the rabbit PrP open reading frame
      (ORF) was cloned and characterised. There is 82-87% identity at the nucleotide
      sequence level and 88-93% identity at the amino acid (aa) sequence level, between
      the rabbit gene and PrP sequences of other mammals. The rabbit gene shares
      structural and organisational features common to all known PrP genes signifying
      that it is the rabbit PrP gene. Comparison of the rabbit PrP aa sequence with PrP
      aa sequences from different species revealed several potential epitopes. Two anti
      ovine PrP peptide Ab raised in rabbits, 168-92 and 98-92, confirmed that two
      separate cross-reacting epitopes segregate with single aa differences between
      rabbit and sheep PrP at positions 43 and 99 of the rabbit PrP polypeptide. The
      presence of these epitopes correlates with the species recognition patterns of
      previously published Ab. The usefulness of the rabbit PrP gene sequence in
      predicting antigenic regions within the PrP proteins of various species is
      illustrated. The structure of the rabbit PrP protein in relation to rabbits
      apparent resistance to infection by prions is discussed.

PMID- 9031632
TI  - The nucleotide sequence and predicted secondary structure of small subunit (18S)
      ribosomal RNA from Spirometra erinaceieuropaei.
AB  - The nucleotide (nt) sequence of a small subunit (18S) ribosomal RNA gene from the
      plerocercoid of Spirometra erinaceieuropaei (SEP) was determined. The gene with
      2182 bp in length is larger than that of most eukaryotes. Extra nt sequences
      occur in regions known to be variable (V4 and V7). The predicted secondary
      structure of the nt positions 679-933 (V4) revealed different helices from that
      of other eukaryotes. The region between nt positions 1540 and 1749 (V7) was
      different from that of other eukaryotes, but the secondary structure prediction
      by computer analysis demonstrated that this part of 18S rRNA sequence from S.
      erinaceieuropaei may form a single extended helix. Nt that were aligned with
      those of nine other parasites were used to estimate phylogenetic relationships.
      The data presented here clearly indicate that S. erinaceieuropaei is closely
      related to Echinococcus granulosus.

PMID- 9031633
TI  - Conservation of a putative inhibitory domain in the GAL4 family members.
AB  - The GAL4 family members are fungal transcriptional activators composed of several
      functional domains: a characteristic cysteine-rich DNA-binding domain common to
      all members, a dimerization domain, various transactivation domains generally
      exhibiting a high acidic content and a highly variable central region supposed to
      be involved in regulation and in effector recognition. We report here that the
      central region of the GAL4 family members share eight conserved motifs embedded
      in a large functional domain of 225 up to 405 residues. This domain may also be
      present in four proteins belonging to another family of transcriptional
      activators sharing a C2H2-type zinc finger. Analysis of the biochemical data
      available on the well-studied GAL4 protein suggests that this domain may be
      involved in the regulation of the activity of the protein, particularly in an
      inhibitory function. This hypothesis is further supported by deletion and site
      directed mutagenesis experiments on other GAL4 family members. The mean secondary
      structure prediction performed on the eight motifs strongly suggests that the
      inhibitory activity may be mediated by hydrophobic interactions linked to the
      presence of amphipathic alpha-helices.

PMID- 9031634
TI  - Studies of the mouse Rab geranylgeranyl transferase beta subunit: gene structure,
      expression and regulation.
AB  - The mouse Rab geranylgeranyl transferase beta (Rab GGTase beta) catalytic subunit
      gene was isolated and characterized. This gene (Rabggtb) spans a distance of
      approx. 7 kb and is organized into eight exons. All the exon/intron junction
      sequences follow the GT/AG rule. Multiple transcription initiation sites are
      located within 384 bp upstream from the translation start codon. The 5'-flanking
      region contains several potential binding sites for transcription factors, but no
      TATA box is identified in this region. Expression of this gene was detected in
      all the major organs in adult animals. In mouse embryos, its expression was
      examined by in situ hybridization. Specific expression of this gene was elevated
      in mid-gestation stages, particularly developing liver and spinal cord. Northern
      blot analysis of an embryonic carcinoma cell line P19 showed that the steady
      state level of Rabggtb mRNA expression was increased dramatically by
      cycloheximide (CHX) treatment as early as 2 h, suggesting a role of post
      transcriptional regulation of Rab GGTase beta gene expression. Actinomycin D was
      used to determine the half-life of Rab GGTase beta transcripts CHX treatment
      resulted in a dramatic increase of the half-life of Rab GGTase beta transcripts,
      from 8 h to greater than 12 h.

PMID- 9031635
TI  - Molecular cloning of a putative serotonin receptor gene from barnacle, Balanus
      amphitrite.
AB  - We isolated a putative serotonin receptor gene from a genomic library of the
      barnacle, balanus amphitrite Darwin, using an Ncol fragment of the barnacle G
      protein-coupled receptor gene that is homologous to the alpha 2-adrenoceptor. The
      cloned genomic DNA had no intron and specified an open reading frame of 1137 base
      pairs encoding 379 amino acids (aa). The predicted aa sequence has a typical
      seven hydrophobic transmembrane spanning region and a consensus G protein-binding
      motif. This receptor was most homologous to the human 5HT1A receptor and closely
      related to other 5HT1 receptor subtypes.

PMID- 9031636
TI  - Bacillus subtilis bacteriophage SPP1 terminase has a dual activity: it is
      required for the packaging initiation and represses its own synthesis.
AB  - The B. subtilis bacteriophage SPP1 terminase, encoded by genes 1 and 2, is
      required for the initiation of headful packaging. The DNA segment to which gene 1
      product (G/P) binds includes the pacL and pacR sites and the late PL1 and PL2
      promoters from which genes 1 to 7 are transcribed. When SPP1wt or SPP1sus115
      (gene 6-) phages were used to infect a B. subtilis sup0 strain, the gene 1 to 7
      mRNA synthesis was reduced at late times of infection. This was not observed,
      however, when either chloramphenicol was added 7 min after infection with SPP1wt
      or when SPP1sus114 (gene 1-) or SPP1sus19 (gene 2-) were used to infect B.
      subtilis sup0 cells. These results suggest that the terminase enzyme functions as
      a repressor of its own transcription. G/P and B. subtilis RNA polymerase (RP)
      bind to the pacL segment, which contains the PL1 and PL2 promoter region. The
      binding of G/P to the pacL site does not seem to exclude RP from the promoters,
      despite of the overlapping of their binding sites. It is likely that the
      terminase protein does not repress transcription by a mere steric hindrance of RP
      binding.

PMID- 9031637
TI  - Discovery of a Zdel transposable element in Zea species as a consequence of a
      retrotransposon insertion.
AB  - Nucleotide sequences similar to del1 retrotransposon from Lilium henryi have been
      discovered in Zea diploperennis as a consequence of finding a Zea retrotransposon
      element inserted into one of them. These sequences named Zdel (Zea del1-like)
      elements are present in all the Zea species (about 100 copies per haploid genome)
      and in Tripsacum dactyloides and absent from closely related genera. Sequences
      corresponding to gag and protease domains from a Zdel element have been
      identified. The Zdel protease sequence shows a conserved active site motif
      (DT/SG) from aspartic proteases. The high level of DNA methylation found in Zdel
      elements may be related to the observed absence of transcriptional activity.

PMID- 9031638
TI  - A selection system to study C5a-C5a-receptor interactions: phage display of a
      novel C5a anaphylatoxin, Fos-C5aAla27.
AB  - Binding and effector domains of the human anaphylatoxin C5a have been determined
      by either site directed mutagenesis or synthetic peptide studies. However, the
      lack of specific selection methods, which allow direct investigation of C5a-C5a
      receptor interaction made these studies laborious. To overcome these limitations
      we have constructed a novel Fos-C5a expressed on the tip of a filamentous phage.
      To guarantee for a free C-terminus which is required for C5a activity C5a cDNA
      was cloned into the phagemid vector pJuFo. Helper phage infection of pJuFc-C5a
      transformed cells resulted in a mutant phage displaying Fos-C5a on its surface.
      However studies with Bt2cAMP differentiated U937 cells revealed that phage
      displayed Fos-C5a is functional inactive. Subsequently we replaced a nonconserved
      cysteine residue at position 27 by alanine and obtained Fos-C5aAla27. Both the
      purified and the phage displayed Fos-C5aAla27 proteins were functional active and
      induced enzyme release from differentiated U937 cells. In addition, purified Fos
      C5aAla27 exhibited the same binding profile as compared to rhC5a. Fos-C5aAla27
      displaying phages were mixed with phage harboring only the pJuFo plasmid at a
      ratio of 10(6). After four successive rounds of panning on differentiated U937
      cells Fos-C5aAla27 phages were enriched to 100% as shown by C5a-specific ELISA.
      We expect this approach to prove helpful for studying C5a-C5a-receptor
      interactions. i.e. to screen C5a libraries for high affinity binders with
      agonistic or antagonistic properties directly on cells.

PMID- 9031639
TI  - Cloning and characterization of two processed pseudogenes and the cDNA for the
      murine U1 snRNP-specific protein C.
AB  - Genes for the snRNP proteins U1-70K, U1-A, Sm-B'/B, Sm-D1 and Sm-E have been
      isolated from various metazoan species. The genes for Sm-D1 and Sm-E, which were
      isolated from a murine and human source respectively, appear to belong to a
      multigene family. It has been suggested that also for the mammalian U1-C protein
      such a multigene family exists. With the human U1-C cDNA as a probe, two genes
      containing sequences homologous to the probe sequence were isolated from a mouse
      genomic library. Simultaneously, a murine U1-C cDNA was isolated from a mouse
      cDNA library. This 0.74 kb cDNA contains an open reading frame (ORF) of 477 bp
      encoding a polypeptide of 159 amino acids (aa) which differs at only one position
      (position 65) from the human U1-C protein. One of the isolated U1-C genes
      contains an ORF as well and shares 92% nucleotide sequence identity with the
      mouse U1-C cDNA. The features of this gene, in particular the absence of introns,
      the acquisition of a 3' poly(A) tail and flanking direct repeats, indicate that
      it represents a processed pseudogene. At the predicted aa sequence level,
      substitutions of conserved residues at functionally important positions are
      observed, strongly suggesting that expression of this gene would not lead to a
      functional polypeptide. The second U1-C gene appeared to be a pseudogene as well
      because it is also intronless and contains a frameshift mutation compared to the
      ORF in the mouse U1-C cDNA. The characterization of these two pseudogenes points
      to the existence of a U1-C multigene family in mice. Furthermore, comparison of
      aa sequences of the murine, human and Xenopus U1-C shows that the protein is
      highly conserved through evolution. Since the Xenopus U1-C differs from the two
      mammalian counterparts solely at a number of positions in the C-terminal region,
      it can be concluded that aa changes are less well tolerated in the N-terminal
      region of U1-C than in the rest of the protein.

PMID- 9031640
TI  - Adenovirus E1a interferes with expression of vaccinia viral genes.
AB  - The 12S and 13S cDNAs of the oncogene E1a encoded by the early region of
      adenovirus 12 (Ad12) were overexpressed using the T7/encephalomyocarditis
      (EMC)/vaccinia hybrid expression system. The E1a proteins were stable for at
      least 12 h in monkey epithelial BSC1 cells. The E1a proteins were recognized by a
      rabbit polyclonal antibody and displayed phosphorylation patterns similar to
      those displayed by the E1a proteins expressed in Ad12-transformed cells.
      Expression of E1a proteins by recombinant vaccinia virus led to inhibition of
      vaccinia viral protein synthesis which was observed as soon as 6 h after
      infection. This suppression was mediated by both the 12S and the 13S products of
      Ad12E1a and to a somewhat lesser extent by the 13S product of Ad2E1a. The
      inhibition of vaccinia virus gene expression resulted in enhanced survival of
      vaccinia virus-infected cells. These results suggest that the proteins encoded by
      the E1a sequester a viral or a cellular product(s) that is essential for the
      expression of vaccinia virus-encoded genes.

PMID- 9031641
TI  - The Drosophila DSP1 gene encoding an HMG 1-like protein: genomic organization,
      evolutionary conservation and expression.
AB  - The gene that encodes the dorsal switch protein (DSP1) has been isolated from a
      Drosophila melanogaster cosmid library. It is organized into seven exons and six
      introns. The relative position of the introns within the region coding for the
      high mobility group (HMG) domains are identical to those of vertebrate HMG 1/2
      genes. The close similarity between DSP1 and HMG 1/2 genes strongly suggests that
      these genes derived from a common ancestral gene. DSP1 encodes, at least, two
      distinct mRNAs that differ in the length of their 5'-untranslated region and
      coding sequence. Detailed sequence analysis shows that alternative splicing of
      precursor mRNA gives rise to the two isoform mRNAs found in Drosophila cells.

PMID- 9031642
TI  - Physical and genetic map of the chromosome of Dichelobacter nodosus strain A198.
AB  - A physical map of the chromosome of Dichelobacter nodosus strain A198 was
      constructed using the restriction endonucleases EagI and StuI. Mapping data
      indicated the presence of a single, circular chromosome of 1.54 Mb. The three
      rRNA operons and the virulence related locus (vrl) were precisely positioned at
      the junctions of EagI and StuI fragments, and their transcriptional orientations
      were also determined. Other D. nodosus genes were assigned to specific EagI and
      StuI fragments. Analysis of the resultant map revealed that the putative
      virulence genes were not clustered on the chromosome which suggests that the D.
      nodosus virulence determinants have been acquired gradually and that virulence in
      D. nodosus is an evolving trait.

PMID- 9031644
TI  - A meat ax or a scalpel? A proposal for Medicare reform.

PMID- 9031643
TI  - The P-OLE1 gene of Pichia angusta encodes a delta 9-fatty acid desaturase and
      complements the ole1 mutation of Saccharomyces cerevisiae.
AB  - Three PCR-amplified DNA fragments hybridizing with the OLE1 gene encoding delta 9
      fatty acid desaturase of Saccharomyces cerevisiae were obtained using,
      respectively, genomic DNAs of one strain each of Kluyveromyces thermotolerans,
      Pichia angusta and Yarrowia lipolytica as templates. A gene designated P-OLE1 was
      cloned from the above fragment of P. angusta and sequenced. An open reading frame
      of P-OLE1 encodes a 49.6-kDa protein consisting of 451 amino acid residues, which
      shows high identity (62%) and similarity (89%) to that deduced from the OLE1
      nucleotide sequence. Expression of P-OLE1 driven by the S. cerevisiae GAP
      promoter or its own promoter complemented the ole1 mutation of S.cerevisiae.
      Transcription of P-OLE1 in the native host was suggested to be partially
      repressed by oleic acid in the medium, as was that of OLE1 in S. cerevisiae and a
      similar gene in Y. lipolytica, but that of a similar gene in K. thermotolerans
      was not.

PMID- 9031645
TI  - Let's not neglect Medicaid's vital role in insurance markets.

PMID- 9031646
TI  - Facing up to Medicare's challenges.

PMID- 9031647
TI  - Marital status, spousal coverage, and the gender gap in employer-sponsored health
      insurance.
AB  - Not only do men who work full time earn more than women, but they are more likely
      to receive employer-sponsored health benefits. This paper provides evidence on
      the gender gap in employer-sponsored health insurance. The results indicate that
      the gap is driven largely by the tendency of married women to decline employer
      sponsored insurance in favor of being covered through their husbands. Indeed,
      among single workers, women are more likely than men to be offered insurance.
      These findings call into question the conclusion made by previous researchers
      that employers discriminate against women in the provision of health insurance.

PMID- 9031648
TI  - An examination of the decline in employment-based health insurance between 1988
      and 1993.
AB  - This paper identifies factors associated with the decline in employment-based
      health insurance between 1988 and 1993. The contribution of these factors in
      explaining the decrease in employment-based health coverage over the period is
      explored using regression-based decomposition analysis. Our results indicate that
      decreased percentages of employers sponsoring health insurance plans, reductions
      in real wages, a trend toward using part-time workers, a decline in unionization,
      and the movement of workers across industry sectors account for 24% to 51% of the
      decline in employment-based health insurance coverage between 1988 and 1993.

PMID- 9031649
TI  - The impact of insurance on access to physician services for elderly people with
      arthritis.
AB  - The impact of insurance on access to physician services among elderly individuals
      with chronic illnesses has far-reaching policy implications. Using a national
      probability sample of aged Medicare beneficiaries (N = 5,543), and controlling
      for severity of illness, comorbidities, and other covariates, we analyze this
      issue for the most prevalent, chronic disabling disease among the elderly:
      arthritis. The results from the two-part multivariate model (logistic regression
      followed by ordinary least squares regression) suggest that insurance status is a
      positive and statistically significant predictor of both initial access to care
      (p < .01), and amount of arthritis care used (p < .05). Taking the results of the
      two-part model, we conducted a microsimulation to estimate the increase in
      Medicare spending that would result if various types of Medicare supplemental
      insurance were provided to those who had none. Results suggest that Medicare
      expenditures would rise from $51 million to $59 million annually depending on the
      type of supplement provided.

PMID- 9031650
TI  - Patterns of pharmacy participation in Medicaid: implications for enrollee access.
AB  - Little attention has been given to pharmacy participation in Medicaid and
      enrollee access to pharmacy services despite the potential for treatment problems
      if appropriate drug regimens are not followed. This study presents an economic
      model of pharmacy participation in Medicaid and descriptive and multivariate
      analyses of participation rates. A key variable was the adequacy of Medicaid
      payments for drugs dispensed to Medicaid enrollees. This was found to positively
      affect county-level pharmacy participation and, in turn, participation rates were
      a positive and significant determinant of the number of prescriptions per
      enrollee. Pharmacy location, size, and type also affected participation rates and
      enrollee utilization.

PMID- 9031651
TI  - Insider representation on the governing boards of nonprofit hospitals: trends and
      implications for charitable care.
AB  - Evidence indicates that the traditional, nonprofit hospital governing board,
      which is heavily comprised of community representatives, is changing to favor
      more insiders from the hospital's senior management and medical staff. In this
      study, I examine this trend, as well as the relationship between insider
      representation and the amount of charitable care hospitals provide to their
      community. Study results indicate that insider representation on hospital boards
      increased substantially during the 1980s. The findings also imply that the
      relationship between insider representation and the provision of charitable care
      depends on contextual factors related to the hospital's viability.

PMID- 9031652
TI  - Changes in the use of diagnostic technologies among Medicare patients, 1985 and
      1990.
AB  - This paper examines changes in the use of selected diagnostic technologies for
      Medicare patients in 1985 and 1990. The analysis compares patients across five
      common, medical tracer conditions: acute myocardial infarction (AMI), congestive
      heart failure (CHF), stroke, pneumonia, and gastrointestinal (GI) hemorrhage. The
      relationship of hospital characteristics to patterns of technology use was
      assessed by grouping hospitals by a composite measure of "costliness." The
      overall use of 21 diagnostic tests rose by 27% over the 5-year period. Increases
      were most marked among the three cardiovascular tracers and for related
      technologies, such as cardiac angiography and cardiac ultrasound. There was
      evidence that newer technologies partially replaced older diagnostic tests that
      were used for similar indications: rates of noninvasive cerebrovascular imaging
      rose while rates of cerebral angiography declined. However, for several common,
      long-established tests, such as electrocardiogram and chest radiograph, there
      were consistent increases that are unexplained. High-cost hospitals performed
      diagnostic tests at much higher rates than lower-cost hospitals in both 1985 and
      1990, but the rate of increase in test use across the two study years was
      generally greater for the lower-cost hospitals.

PMID- 9031653
TI  - The Medical Expenditure Panel Survey: a national health information resource.
AB  - This article describes the Medical Expenditure Panel Survey (MEPS), the third in
      a series of nationally representative surveys of medical care use and
      expenditures sponsored by the Agency for Health Care Policy and Research. The
      MEPS is designed to provide extensive data on the types of health care services
      American use, how frequently they use them, how much is paid for the services,
      and who pays for them. It also will provide information on the types and costs of
      private health insurance available to the U.S. population. The survey is
      unparalleled in its degree of detail, as well as its ability to link medical care
      use, payments, and health insurance coverage to specific survey respondents and
      their families. It allows analysts to examine how individual and family
      characteristics, including the characteristics of their health insurance, affect
      medical care use and spending. This article discusses each of the MEPS
      components, focusing on design enhancements that have been made since the survey
      was last conducted nearly a decade ago.

PMID- 9031654
TI  - Orthopaedic proceedings 1995, 1996. Abstracts.

PMID- 9031655
TI  - 75th General session of the International Association in Dental Research.
      Orlando, Florida, March 19-23, 1997. Abstracts.

PMID- 9031656
TI  - What to do with Stella? The case of the near-incompetent employee nearing
      retirement.

PMID- 9031657
TI  - Overview of the regional collaboratives.
AB  - Responding to demands that nursing leaders conduct business in creative,
      proactive ways, the authors of this department share the work of The Robert Wood
      Johnson Foundation's national program. Colleagues in Caring: Regional
      Collaboratives for Nursing Work Force Development. The purpose of this initiative
      is to enhance regional and state collaborative planning and implement actions and
      policies to address the rapid changes occurring in the United States nursing
      labor market. This department presents the ongoing work of the program,
      highlighting the work of the 20 individual collaboratives. Regional approaches to
      the expected program outcomes and specific challenges and opportunities that are
      unique to each region's environment are included. The Colleagues in Caring
      program is administered by the American Association of Colleges of Nursing.
      Current information on the initiative can be found at http:/(/)www.aacn.nche.edu
      under Special Projects. The staff at the National Program Office can be reached
      at 202/496-1095 (fax: 202/496-1093).

PMID- 9031658
TI  - Tracking changes in the public health system.

PMID- 9031660
TI  - Nursing staff time allocation in long-term care: a work sampling study.
AB  - The effective use of nursing staff time is a major determinant of the quality of
      care in long-term care facilities. The purpose of this work sampling study was to
      identify those activities that consumed the largest amount of staff time on a
      locked unit housing: 60 chronically ill and demented patients. A heavy work load,
      large proportion of direct care, and minimal nonproductive time were found. Work
      redesign strategies to improve staff efficiency and implications for further
      research are discussed.

PMID- 9031659
TI  - The use of nurse practitioners in the acute care setting.
AB  - A collaborative practice model was initiated in a university hospital to assist
      resident physicians to coordinate patient care on specialty services. Nurse
      practitioner (NP) data were collected on daily work activities and categorized as
      direct care, indirect care, administration, education, and research. Satisfaction
      surveys were collected from patients, physicians and nursing staff. Data on
      clinic evaluation and management service provided by the NPs were reported. The
      study supported the appropriateness of NPs in the acute care setting.

PMID- 9031662
TI  - Delegation decision making. Evaluation of a teaching strategy.
AB  - Delegation and coordination of patient care is an important role for registered
      nurses practicing in hospitals. Educational programs and clinical experience have
      not prepared most registered nursing function in the delegation decision-making
      role. The author describes how the use of the Nursing Assessment Decision Grid
      increased the knowledge base in delegation decision-making skills for medical
      surgical nurses practicing in a 282-bed tertiary hospital in central Alabama.

PMID- 9031661
TI  - Pro-ACT II: integrating utilization management, discharge planning, and nursing
      case management into the outcomes manager role.
AB  - Building on redesign efforts that created case management, clinical care
      technicians, support service hosts, and pharmacy technician roles, this redesign
      focused on integrating case management, utilization management, and discharge
      planning functions into a new outcomes manager role. The authors describe the
      process of developing and implementing the new role and outline specific actions
      that eliminated redundancy and inefficiency. Results of the evaluation of the
      project are reviewed, including full-time equivalent and salary savings and
      employee and physician satisfaction improvements.

PMID- 9031663
TI  - Nidulal, a novel inducer of differentiation of human promyelocytic leukemia cells
      from Nidula candida.
AB  - Nidulal (1), a novel inducer of differentiation of human HL-60 promyelocytic
      leukemia cells, was isolated from fermentations of the basidiomycete Nidula
      candida together with low amounts of niduloic acid (2). Both compounds are
      bisabolane sesquiterpenes. Their structures were elucidated by spectroscopic
      methods. In reporter gene assays nidulal (1) preferentially activated the
      transcription factor complex AP-1-mediated expression of secreted alkaline
      phosphatase in COS-7 cells. In addition nidulal (1) and niduloic acid (2)
      exhibited weak cytotoxic and antibiotic activities.

PMID- 9031664
TI  - New antitumor substances, FR901463, FR901464 and FR901465. I. Taxonomy,
      fermentation, isolation, physico-chemical properties and biological activities.
AB  - New antitumor substances, FR901463, FR901464 and FR901465 were isolated from the
      culture broth of a bacterium of Pseudomonas sp. No.2663. FR901463, FR901464 and
      FR901465 remarkably enhanced the transcriptional activity of the promoter of SV40
      DNA virus. Further, these compounds exhibited potent antitumor activities against
      murine and human tumor cell lines in vitro.

PMID- 9031665
TI  - New antitumor substances, FR901463, FR901464 and FR901465. II. Activities against
      experimental tumors in mice and mechanism of action.
AB  - FR901463, FR901464 and FR901465, novel antitumor substances, were isolated from
      the fermentation broth of Pseudomonas sp. No. 2663. Their antitumor activities
      were examined in three mouse tumor systems and one human tumor system. The three
      FR compounds prolonged the life of mice bearing murine ascitic tumor P388
      leukemia (T/C values were 160%, 145% and 127% for FR901463, FR901464 and
      FR901465, respectively), and inhibited the growth of a human solid tumor, A549
      lung adenocarcinoma, with different effective dose ranges. FR901464 exhibited
      most prominent effects on these tumor systems among the three FR compounds.
      FR901464 also inhibited the growth of murine solid tumors, Colon 38 carcinoma and
      Meth A fibrosarcoma. To address the involvement of transcriptional activation
      ability of the three FR compounds in the antitumor effect, we selected FR901464
      as a candidate compound and investigated cell cycle transition, chromatin status
      and endogenous gene expression in FR901464-treated tumor cells having elevated
      transcriptional activity. FR901464 induced characteristic G1 and G2/M phase
      arrest in the cell cycle and internucleosomal degradation of genomic DNA with the
      same kinetics as activation of SV40 promoter-dependent cellular transcription in
      M-8 tumor cells. In contrast to the potent activation of the viral promoter,
      FR901464 suppressed the transcription of some inducible endogenous genes but not
      house keeping genes in M-8 cells. These results suggest that FR901464 may induce
      a dynamic change of chromatin structure, giving rise to strong antitumor
      activity, and therefore may represent a new type of drug for cancer chemotherapy.

PMID- 9031666
TI  - TMC-1 A, B, C and D, new antibiotics of the manumycin group produced by
      Streptomyces sp. Taxonomy, production, isolation, physico-chemical properties,
      structure elucidation and biological properties.
AB  - Four new antitumor antibiotics, TMC-1 A, B, C and D were isolated from a
      fermentation broth of Streptomyces sp. A-230. Spectroscopic studies have shown
      that TMC-1 A to D were new members of the manumycin class of antibiotics. These
      antibiotics showed cytotoxic activities against various tumor cell lines in
      vitro.

PMID- 9031667
TI  - Antifungal antibiotic benanomicin A increases susceptibility of Candida albicans
      to phagocytosis by murine macrophages.
AB  - Benanomicin A is an antifungal antibiotic produced by Actinomadura spadix. In the
      present study, we investigated the effect of benanomicin A on the phagocytosis of
      Candida albicans by murine peritoneal macrophages and on the cell-surface
      hydrophobicity (CSH) of C. albicans. Although pretreatment of macrophages with
      benanomicin A had no effect on the phagocytosis, addition of benanomicin A to the
      culture of macrophages and Candida cells increased the susceptibility of Candida
      cells to the phagocytosis by the macrophages. Pretreatment of Candida cells with
      benanomicin A also increased the susceptibility of Candida cells to the
      phagocytosis. When Candida cells were mixed with benanomicin A, the antibiotic
      bound irreversibly to Candida cells. These data suggest the possibility that the
      increased susceptibility of Candida cells to the phagocytosis is mediated by the
      binding of benanomicin A to Candida cells. Examination of physicochemical
      property of Candida cell surface showed that the CSH of Candida cells
      significantly decreased by the treatment with benanomicin A. Thus, binding of
      benanomicin A to Candida cells may induce biochemical/physicochemical alternation
      of the surfaces, so that they become more susceptible to phagocytosis by murine
      macrophages. These properties of benanomicin A, along with its antifungal
      activity, seem to be beneficial in the treatment of fungal infections.

PMID- 9031668
TI  - UK-2A, B, C and D, novel antifungal antibiotics from Streptomyces sp. 517-02. II.
      Structural elucidation.
AB  - UK-2A, B, C and D, novel antibiotics produced by Streptomyces sp. 517-02, exhibit
      strong antifungal activity. The structures were elucidated based on spectral and
      chemical evidence that these compounds are the derivatives of the nine-membered
      dilactone formed from serine and 4-hydroxypentanoic acid moiety.

PMID- 9031669
TI  - Stereostructure of amphotericin A.

PMID- 9031670
TI  - Synthesis and antibacterial activity of derivatives of the glycopeptide
      antibiotic A-40926 and its aglycone.
AB  - Starting from the antibiotic A-40926 and the aglycone of A-40926 a series of
      compounds were prepared by modifying the free functionalities. Their
      antimicrobial activity was determined, particularly against Neisseria
      gonorrhoeae, against which A-40926, unlike other natural glycopeptides, is
      active. Improved in vivo activity was displayed by the monomethyl ester of A
      40926 esterified at the carboxyl group of the N-acylamino-glucuronyl moiety.

PMID- 9031672
TI  - Novel C-2 substituted carbapenem derivatives. Part I. Synthesis and biological
      activity of non-aromatic heterocyclic derivatives.
AB  - A new series of carbapenems, having a saturated or partially unsaturated
      heterocycle at C-2, has been synthesised. The in vitro antibacterial activity of
      these compounds and their stability to human dehydropeptidase-1 (DHP-1) are
      described. The stereochemistry of the C-2 side-chain and the presence of a double
      bond in the heterocycle were shown to have significant effects on the stabilities
      of the compounds to DHP-1.

PMID- 9031671
TI  - Synthesis and biological evaluation of new fragments from kirromycin antibiotic.
AB  - New N-acyl derivatives of 1-N-desmethyl goldinamine were obtained from
      degradation of kirromycin. Periodate-oxidation of these derivatives provided new
      aldehydic fragments that were further elaborated. Both N-phenyl ureido and N
      phthalimido derivatives of 1-N-desmethyl goldinamine are able to inhibit
      bacterial protein synthesis in cell-free assay and are active against whole
      microorganisms, although with lower potency than kirromycin. The derivatives from
      the aldehydic fragments are totally inactive.

PMID- 9031673
TI  - Novel C-2 substituted carbapenem derivatives. Part II. Synthesis and structure
      activity relationships of isoxazolin-2-yl, isoxazolidin-2-yl and 2-pyrazolin-2-yl
      carbapenems generated using 1,3-dipolar cycloaddition chemistry.
AB  - A series of carbapenems containing novel C-2 semisaturated heterocyclic
      substituents were synthesised by 1,3 dipolar cycloaddition reactions of nitrile
      oxides, nitrile imines and a nitrone to 2-vinylcarbapenem. The isoxazoline and
      isoxazolidine compounds showed potent antibacterial activity but moderate
      stability to human dehydropeptidase 1 (DHP-1). Stability to DHP-1 was improved by
      methyl substitution in the isoxazoline ring, but at the expense of antibacterial
      activity. The pyrazolines exhibited excellent stability to DHP-1, but reduced
      potency against Gram-negative organisms.

PMID- 9031674
TI  - 41-Demethylhomooligomycin B, a new immunosuppresant antibiotic from Streptomyces
      ostreogriseus.

PMID- 9031675
TI  - Andrastin D, novel protein farnesyltransferase inhibitor produced by Penicillium
      sp. FO-3929.

PMID- 9031676
TI  - NK154183A and B, antitumor substances produced by Streptomyces sp.

PMID- 9031678
TI  - Synthesis and biological activity of quaternary ammoniopropenylcephalosporins
      with hydroxylated alicyclic or aliphatic amines.

PMID- 9031677
TI  - Isolation of nicotianamine as a gelatinase inhibitor.

PMID- 9031679
TI  - Radiation protection by alpha-methyl-homocysteine thiolactone in vitro.
AB  - The radiation protective effect of thiol compounds is unequivocal and their use
      is only limited by their toxic effects. We used the principle of alpha
      alkylation, which renders amino acids unmetabolizable, to reduce the toxicity of
      homocysteine. This product, alpha-methyl-homocysteine thio-lactone, was tested
      for toxicity and radiation protective effect along with known protectors L
      cysteine, cysteamine and WR 1065 in cell culture using V79-4 Chinese hamster lung
      cells. The three-day growth curve assays, useful to measure overall effects on
      cell growth, revealed lowest toxicity for alpha-methyl-homocysteine thiolactone
      (GL-2). Clonogenic survival tests, used to evaluate the retention of reproductive
      integrity, were carried out and revealed that GL-2 had no adverse effects in this
      test system. Radiation protection tests showed that GL-2 exhibited protective
      activity against radiation induced lethality above that seen with cysteine and
      cysteamine, but below WR 1065. However, GL-2 showed little or no negative effects
      toward the cell itself, in direct contrast to WR 1065. Our findings show a
      potentially important tool and principle to reduce toxicity of radiation
      protectors with analogous structures.

PMID- 9031680
TI  - Effects of FR145237, an acyl-CoA:cholesterol acyltransferase inhibitor, on diet
      induced hypercholesterolemia in diabetic rats.
AB  - Recent studies have shown that acyl-CoA:cholesterol acyltransferase (ACAT) plays
      an important role in the initiation of diabetes-associated hypercholesterolemia.
      To confirm this hypothesis, effects of a potent ACAT inhibitor, FR145237, on diet
      induced hypercholesterolemia were examined in streptozotocin (STZ)-induced
      diabetic rats. One-week feeding of 1% cholesterol and 0.5% cholic acid to normal
      rats and STZ-induced diabetic rats increased plasma cholesterol levels in both
      groups, and the response was more remarkable in the STZ rats than in the normal
      ones (1266 +/- 476 mg/dl and 146 +/- 7 mg/dl, respectively). FR145237 dose
      dependently reduced the rise in plasma cholesterol levels in the STZ rats and the
      levels were almost normalized by treatment with 1 mg/kg/day of the compound.
      These results suggest that hyperresponse to dietary cholesterol was induced in
      the STZ rats and that ACAT is involved in the hyperresponse. The effects of
      FR145237 on other plasma lipids such as high density lipoprotein (HDL)
      cholesterol and triglyceride (TG) levels were also examined.

PMID- 9031681
TI  - Red blood cells participate in the metabolic clearance of catecholamines in the
      rat.
AB  - The aim of the present study was to investigate the possible role of erythrocytes
      in the metabolic clearance of catecholamines (CAs) in the rat. Intravenous
      infusion of exogenous CAs (dopamine -DA-, norepinephrine -NE-, or epinephrine 
      Epi-) was carried out at increasing doses to cover a range of plasma
      concentrations from the lower to the upper physiological and to pharmacological
      levels. Whatever the mechanism(s) underlying the CAs erythrocyte/plasma balance:
      1. it seemed more efficient at lower concentrations of CAs; 2. it reached an
      apparent plateau where plasma and erythrocyte concentrations were not
      statistically different; 3. finally, saturation was suggested when further
      increase in plasma concentration was associated with a lower response in
      erythrocytes. This series of experiments confirms previous reported results with
      human erythrocytes and suggests that rat erythrocytes could transport CAs from
      their sites of release to their sites of elimination. In a second series of
      experiments, the intra-erythrocyte metabolism of CAs was investigated. DA was
      strikingly increased in plasma and in erythrocytes 2 hours after 1,2-dimethyl-3
      hydroxy-4-pyridone (CP20), 100 mg/kg i.p., known to inhibit catechol-O-methyl
      transferase. Our data demonstrate an increase in glucuro-conjugated DA in vivo
      (24 hours after CP20 injection) as well as in vitro (3 hours incubation at 37
      degrees C), suggesting activation of the glucuroconjugating pathway. Increased
      glucuroconjugated DA after in vitro incubation demonstrates intra-erythrocyte
      synthesis while increased concentration in Ringer-Hepes medium demonstrates an
      inside-out transport of glucuro-conjugate. These data are the first evidence in
      favour of an intra-erythrocyte glucuro-conjugation of CAs in the rat.

PMID- 9031682
TI  - Cyclo(His-Pro) augments the insulin response to oral glucose in rats.
AB  - Cyclo(His-Pro) (CHP) is a gut-brain peptide found in rat and man. Since plasma
      levels of CHP are altered by oral glucose ingestion, we wondered whether
      exogenous CHP might alter the insulin response to oral glucose ingestion. To this
      end, rats were given 3g/kg oral glucose load with either saline or increasing
      doses of CHP and plasma levels of insulin, C-peptide and glucose were measured.
      We found mean insulin but not C-peptide excursions and area under the insulin but
      not C-peptide response curves (AUC) were significantly higher in the CHP groups
      than controls despite similar glucose responses. In summary, these data show that
      in rats receiving oral glucose, CHP causes higher insulin excursions without any
      change in C-peptide suggesting that CHP may decrease hepatic insulin clearance.

PMID- 9031683
TI  - Thyroid hormone upregulates Na,K-ATPase alpha and beta mRNA in primary cultures
      of proximal tubule cells.
AB  - In vivo studies have demonstrated that thyroid hormone regulates the activity of
      Na,K-ATPase in the mammalian kidney. However, it is still unclear whether
      upregulation of Na,K-ATPase by thyroid hormone is mediated through the direct
      action on renal tubule cells or through other mediators, such as an increase in
      glomerular filtration rate. Using primary cultures of rabbit renal proximal
      tubule cells, studies were undertaken to elucidate this problem. We found that
      Na,K-ATPase activity was increased by 26 +/- 8%, 30 +/- 9%, 39 +/- 9% after 24-h
      treatment with T3 of 10(-11), 10(-9), 10(-7) M, respectively. We further
      demonstrated that 24-h incubation of T3 (10(-7) M) enhanced alpha- and beta
      protein abundance by 44 +/- 29% and 31 +/- 16%, and alpha- and beta-mRNA levels
      by 84 +/- 27% and 65 +/- 11%, respectively. The time course studies revealed that
      the significant increase in Na,K-ATPase activity, alpha- and beta-protein and
      mRNA abundance didn't appear until 24-h of T3 treatment. Our data indicate that
      thyroid hormone directly upregulates Na,K-ATPase in proximal tubule cells via a
      pretranslational mechanism.

PMID- 9031684
TI  - Effect of molsidomine on basal Ca2+ current in rat cardiac cells.
AB  - To determine the effect of molsidomine, a nitric oxide (NO) donor, on basal L
      type Ca2+ current (ICa), the patch-clamp study was performed in single myocytes
      isolated from rat ventricles. External application of molsidomine (10 nM-100
      microM) in the presence of internal Ca2+ (pCa = 6.85) inhibited basal ICa in a
      concentration-dependent manner. In the absence of internal Ca2+ (pCa = infinity),
      molsidomine concentration-dependently stimulated basal ICa. These opposite
      effects of molsidomine on ICa were not found when intracellular cGMP (1 mM) had
      been increased. Regardless of the presence or absence of internal Ca2+, milrinone
      application (20 microM) had a stimulatory effect on ICa in the absence of
      intracellular cGMP. In the continuing presence of milrinone, molsidomine (1-100
      microM) at pCa infinity had no significant effect on the milrinone-enhanced ICa
      which was concentration-dependently inhibited by molsidomine (1-100 microM) at
      pCa 6.85. These results suggest that the inhibitory and stimulatory effects of
      molsidomine on basal ICa in the rat cardiac myocytes are related to an activation
      of the cGMP-dependent protein kinase (cGMP-PK) and an inhibition of the cGMP
      inhibited cAMP-phosphodiesterase (PDE), respectively, and that these different
      actions appear to be mediated by the difference in intracellular Ca2+ levels.

PMID- 9031685
TI  - Gender differences in the generation of superoxide anions in the rat aorta.
AB  - Generation of superoxide anions was measured in the isolated aorta of female and
      male rats using a lucigenin chemiluminescence technique. Aortae from male rats
      produced significantly more O2- (about 34%) than the aortae from female animals.
      Removal of endothelium reduced generation of O2- in the aorta of male and female
      rats by 23.9 +/- 1.3 and 15.3 +/- 2.3 pmole O2- min-1 mg-1 dry weight (p < 0.05),
      respectively. The denuded aortae of both sexes showed no different O2-
      production. Generation of O2- could not be influenced by inhibition of
      cycloxygenase with indomethacin or xanthine oxidase with oxypurinol. In contrast
      to the generation of O2- under basal conditions, stimulated generation of O2- by
      either addition of phorbol 12-myristate 13-acetate (to stimulate protein kinase
      C) or diethylthiocarbamate (to inhibit vascular superoxide dismutase activity)
      showed no significant gender differences. It is concluded that the endothelium
      from male rats produces more O2- under basal conditions than the endothelium from
      female rats.

PMID- 9031686
TI  - Expression and localization of inhibin/activin subunits and activin receptors in
      the normal rat prostate.
AB  - Activin, a member of transforming growth factor beta (TGF beta), plays an
      important role during embryonic development, and defects of this growth factor
      results in degenerative disorders as demonstrated by gene knock out studies. TGF
      beta has been shown to have dual effects on the regulation of growth of prostate
      cancer cells. Recently, we have reported that activin was localized and messenger
      RNAs encoding activin and its receptors were expressed in human prostate cancer
      cells. To determine whether normal prostate cells produce inhibin and/or activin,
      immunohistochemistry was conducted on rat prostate glands using specific
      antibodies for inhibin and activin. The inhibin and activin were present in the
      cytoplasm and nuclei of epithelial cells whereas stromal cells were not stained.
      The expression of mRNA for the inhibin/activin subunits was determined using both
      in situ hybridization and the reverse transcription-polymerase chain reaction (RT
      PCR) technique. In addition, the identity of the cDNA product of RT-PCR was
      verified with DNA sequencing. These findings suggest that inhibin is only
      produced and mRNA encoding the alpha-subunit for inhibin is only expressed in the
      normal rat prostate but activin and its receptors are produced and expressed in
      both normal rat prostate as well as human prostate cancer cells.

PMID- 9031687
TI  - Transglutaminase-synthesized spermine derivative of substance P recognizes rat
      portal vein neurokinin-3 receptors.
AB  - The effects of the transglutaminase-synthesized polyamine derivatives of
      Substance P (SP) have been further characterized by their ability to contract in
      vitro the rat portal vein strip (RPV), a pharmacological preparation particularly
      rich in NK-3 receptors. The effects of selective agonists of NK-1, NK-2 and NK-3
      receptors [Sar9,Met(O(2))11]SP, beta-Ala8 NKA(4-10), and senktide respectively,
      were also evaluated by measuring RPV concentration-response curves. Peptide [GR
      82334 (NK-1) and MEN-10,376 (NK-2)] and nonpeptide [WIN 51,708 (NK-1) and SR
      142801 (NK-3)] NK receptor antagonists were used to confirm the participation of
      the different NK receptors to contractile response. Our results demonstrated that
      the spermine derivative of SP (Spm-SP), previously shown to be unable to
      recognize NK-1 and NK-2 receptors in some bioassays, contracts RPV (EC50 = 588
      nM) better than the native neuropeptide (EC50 = 1120 nM). A pretreatment with
      thiorphan, an inhibitor of neutral endopeptidases, significantly reduced such a
      difference. While this inhibitor shifts the SP concentration-response curves to
      the left (EC50 = 720 nM) the action of Spm-SP and [Sar9,Met(O(2))11]SP were
      completely thiorphan-resistant. In the absence of thiorphan we found the
      following rank order of potency: senktide > > beta-Ala8 NKA(4-10) >
      [Sar9,Met(O(2))11]SP = Spm-SP > SP. Among the mentioned NK receptor antagonists,
      only the selective NK-3 receptor antagonist, SR 142801, shifted to the right Spm
      SP and [Sar9,Met(O(2))11]SP concentration-response curve, showing pKB values of
      5.84 and 5.88, respectively. Therefore, the reported results suggest that the
      introduction of a Spm moiety into the SP alters the parent peptide molecule by
      increasing its affinity for NK-3 receptors and/or by preventing its degradation
      by some proteolytic enzymes.

PMID- 9031688
TI  - Effect of endotoxin on gentamicin pharmacokinetics in old and young adult rats.
AB  - The effect of endotoxin administration on gentamicin pharmacokinetics in young
      adult (2-3 months) and old (22-24 months) rats was studied. Gentamicin (3 mg/kg,
      iv) was administered 24 hours after an endotoxin challenge (5 mg/kg, ip). Some
      blood biochemical parameters, viz. urea, AST, GGT activities in addition to PCV
      and Hb concentration and creatinine clearance were also measured. In young
      animals, endotoxin caused prolongation in gentamicin half life (t1/2), increased
      area under the plasma concentration-time curve (AUC) and reduced total body
      clearance (ClB) and volume of distribution (Vd). Endotoxin effects in the old
      rats were qualitatively similar to those induced in the young but were more
      pronounced. They included more than 10 fold increase in the t1/2 and AUC. In
      addition, a rising early phase in gentamicin plasma concentration was noticed in
      old rats treated with endotoxin which was, probably, due to an early
      redistribution process of gentamicin. The results indicate that aging and
      endotoxin, individually, can significantly alter gentamicin pharmacokinetics in
      the rat. These alterations were exacerbated when endotoxemia was induced in old
      rats.

PMID- 9031690
TI  - Serotonergic mediation of fenfluramine discriminative stimuli in fawn-hooded
      rats.
AB  - Fenfluramine, a drug that induces increased synaptic serotonin, was used to train
      Fawn-Hooded rats in a drug discrimination paradigm. This strain of rats is
      thought to possess a genetic serotonin storage abnormality. The intent of the
      study was to see if the Fawn-Hooded rat was similar or dissimilar to the more
      frequently used strain of Sprague-Dawley rat in its ability to learn to
      discriminate 2.0 mg/kg fenfluramine administered intraperitoneally. In addition,
      drugs presumed to work upon central serotonergic neurons were given to the
      fenfluramine-trained Fawn-Hooded rats to investigate if the cueing properties of
      the training drug generalized to other agents. Results indicate that the Fawn
      Hooded rats learn to discriminate fenfluramine from its vehicle at the same rate,
      and with a similar sensitivity to lower doses, as do the Sprague-Dawley rats.
      Furthermore, fenfluramine was shown to completely generalize to MDMA (over 90%);
      TFMPP, m-CPP, quipazine and fluoxetine produced intermediate results (over 70%)
      and 5-MeODMT and ibogaine were vehicle-like (less than 70%). As these results
      coincide with those previously found in Sprague-Dawley rats, the conclusion is
      that the functional capacity to discriminate fenfluramine appears to be like that
      of other rat lines, and serotonergically-mediated, in the Fawn-Hooded rat.
      Suggestions to explain these results are offered and discussed.

PMID- 9031689
TI  - Transient CRE- and kappa B site-binding is cross-regulated by cAMP-dependent
      protein kinase and a protein phosphatase in mouse splenocytes.
AB  - Cyclic AMP regulates a variety of cellular responses through activation of cAMP
      dependent protein kinase (PKA). The catalytic subunit of PKA, in turn, activate
      cAMP responsive element (CRE) and nuclear factor-kappa B (NF-kappa B) binding
      proteins. In this study, we demonstrated that binding activity to both CRE and
      kappa B sites in nuclear extracts from spleen cells is modulated by PKA in a time
      dependent manner. Electrophoretic mobility shift assays showed that binding by
      transcription factors to either the CRE or kappa B motif was rapidly up-regulated
      by cAMP, with maximum binding detected at 30 min in response to forskolin
      stimulation of splenocytes. This was followed by a steady decline in CRE and
      kappa B thereafter reaching basal levels by 2 hr. This up-regulation in CRE and
      kappa B binding was closely associated with an enhancement of PKA activity which
      was maximum at 30 min following forskolin stimulation. However, unlike the
      binding of regulatory factors to CRE and kappa B motifs which was very transient,
      peak PKA activity was sustained for 2 hr. Interestingly, okadaic acid, a protein
      phosphatase inhibitor, prevented the decline in protein binding to CRE and kappa
      B motifs 2 hr following forskolin stimulation and actually produced a slight
      increase at 30 min. These data suggest that binding by transcription factors to
      CRE and kappa B sites are up-regulated concomitantly with PKA activation but
      subsequently down-regulated by a protein phosphatase.

PMID- 9031691
TI  - British Thoracic Society Winter meeting. London, United Kingdom, 9-11 December
      1996. Abstracts.

PMID- 9031698
TI  - Effects of pH and thiocyanate on hydrogen peroxide-induced evolution of molecular
      oxygen in human mixed saliva.
AB  - Hydrogen peroxide-induced evolution of molecular oxygen was measured with a Clark
      type electrode in a buffered reaction mixture containing mixed whole or dialysed
      saliva. The optimum pH for oxygen evolution in mixed whole saliva was around 8.
      Oxygen evolution was also observed in dialysed saliva, suggesting that free SCN-
      is not essential. The optimum pH was around pH 6. Sodium thiocyanate inhibited
      the oxygen evolution under acidic conditions in dialysed saliva, increasing the
      K(m) of hydrogen peroxide and decreasing the Vmax. Ferric chloride (1 mM), a
      chelator of SCN-, also inhibited oxygen evolution in dialysed saliva; activity
      was completely restored by 10 mM sodium citrate. Under alkaline conditions, NaSCN
      slightly enhanced the oxygen evolution without affecting the K(m) of hydrogen
      peroxide but increasing the Vmax. Hydrogen peroxide-induced oxidation of SCN- in
      dialysed saliva was much faster at pH 5 than pH 8. These findings suggest that a
      function of peroxidase in stimulated saliva where the pH is typically between 7
      and 8 is the scavenging of hydrogen peroxide to produce molecular oxygen but
      without producing OSCN- plus HOSCN.

PMID- 9031699
TI  - Expression of genes for bone morphogenetic proteins and receptors in human dental
      pulp.
AB  - Bone morphogenetic proteins (BMP) have been shown to induce reparative dentine
      formation experimentally but the cells responsible, which respond to BMPs, have
      not been identified. The BMP signal is probably mediated by interaction of type I
      and II BMP receptors (R). Here, the RNA of human adult dental pulp and pulp cells
      in culture was examined by reverse transcription (RT) polymerase chain reaction
      (PCR) for evidence of mRNA for BMPs. mRNAs for BMP-2, -4, osteogenic protein-1,
      ActR-1 (activin-like kinase receptor), BMPR-IA, -IB and -II were detected by RT
      PCR. The 698-bp PCR fragment for BMPR-IB was used to probe pulp cells for
      expression of that receptor. Cell expression of BMPR-IB was detected by the
      hybridization probe. The findings suggest that resident pulp cells may be able to
      respond to BMPs to initiate tissue formation.

PMID- 9031700
TI  - The immunohistochemical localization of signal-transduction pathway components
      Jak1, Jak2, Jak3, Tyk2 and STAT-1 during early enamel and dentine formation in
      rat molars.
AB  - This study sought to localize immunohistochemically Janus kinase (Jak) and Tyk
      isoforms and STAT-1 in association with events involved in early dentine and
      enamel formation in the rat molar. The Jaks and STATs (signal transducers and
      activators of transcription) are key signal-transduction pathway components in
      the cytokine receptor-linked pathway. The histological sections were not
      demineralized or fixed, providing optimum conditions for immunohistochemical
      localization. It appears that all of the Jak isoforms and STAT-1 are involved in
      enamel formation. Jak2 and STAT-1 colocalized in the proximal ends of
      presecretory and secretory-stage ameloblasts, supporting work by others that
      growth hormone receptor is located at that site. The colocalization of Jak1, Jak2
      and STAT-1 along the proximal ends of presecretory and secretory ameloblasts
      suggests that the interferon receptor is up-regulated in these cells as well.
      Also, colocalization of Jak3 and STAT-1 in the proximal ends of the ameloblasts
      and the cells of the stratum intermedium predicts the location of the interleukin
      7 receptor in those locations. Jak1, Tyk2 and STAT-1, but not Jak2 or Jak3, stain
      was seen in the odontoblasts.

PMID- 9031701
TI  - The mechanical or metabolic function of secondary osteonal bone in the monkey
      Macaca fascicularis.
AB  - Secondary osteonal bone is believed by many to serve a mechanical function,
      altering the properties and/or orientation of bone in response to fluctuating
      mechanical demands or in the prevention and/or repair of fatigue microdamage.
      Based on this belief, secondary osteons should be concentrated mainly in regions
      experiencing high peak-strain conditions. Others contend that secondary osteonal
      bone functions primarily in meeting the body's calcium needs, and should be
      expected to form principally in low peak-strain regions so as to avoid
      compromising the mechanical strength of the bone. These two hypotheses were
      tested by examining the distribution of secondary osteonal bone in both
      relatively high- and low-strain regions of the macaque face. Previous strain
      gauge studies have demonstrated a steep strain gradient in the macaque face, with
      relatively high peak strains in the anterior portion of the zygomatic arch and in
      the mandibular corpus. Relatively low peak strains have been found in the
      posterior portion of the zygomatic arch and supraorbital bar. Results presented
      here show that in the mature macaques, there is no consistent relation between
      newly forming secondary osteons (i.e. those labelled with fluorescent dyes) and
      peak strain levels. From these data it is concluded that, in the non-perturbed
      adult, either mechanical and metabolic factors contribute equally to the observed
      pattern or that metabolically driven remodelling is initiated without regard to
      strain levels. In immature macaques, however, the relation between peak strain
      levels and secondary osteon density is positive, with a significantly higher
      density of labelled osteons in the high strain regions. From these data it is
      concluded that, in immature individuals, mechanical factors are predominantly
      responsible for the initiation of secondary osteonal remodelling.

PMID- 9031703
TI  - Use of N-phenylmethazonium methosulphate oxidation of NADH in the quantification
      of oxygen uptake by oral bacteria under open-system conditions.
AB  - Technically, open systems are more suited than closed systems for the measurement
      of oxygen uptake by bacteria present at high cell densities as in dental plaque.
      Moreover, measurements are easier to perform and can be done faster and
      continuously. However, quantifications is more difficult and, except for steady
      state conditions, has been semiquantitative. The stoichiometric oxidation of NADH
      by N-phenylmethazonium methosulphate (PMS) is a reaction used here to develop a
      formula that overcomes this problem and makes it possible to relate
      quantitatively the pO2 measured easily with an oxygen electrode to the amount of
      oxygen utilized by respiring bacteria provided with a given amount of substrate.
      The approach and formula consist of the summing of (i) the oxygen decrease
      observed during the period of bacterial oxygen consumption and (ii) the oxygen
      simultaneously entering from the atmosphere. To quantify the entry component, the
      rate of oxygen diffusion into the mixture needed to be determined: this was done
      by reducing or exhausting the oxygen content of the medium in various ways and
      determining the rate constant of atmospheric oxygen entry. The relation between
      the logarithm of the oxygen concentration (determined from pO2 values using the
      PMS-NADH reaction) and point of time in the oxygen resaturation process proved to
      be linear. This enabled calculation of a diffusion rate constant, k, for use in
      the oxygen utilization formula. The validity of this method for quantification of
      oxygen use was tested by comparing oxygen consumption determined from the pO2
      tracing and the derived formula to the oxygen consumed when fixed amounts of NADH
      are oxidized by PMS. When oxygen uptake/substrate utilization molar ratios were
      calculated for each of several NADH concentrations, the resulting values were
      almost identical. The method proved reliable over most of the oxygen
      concentration range possible in this system.

PMID- 9031702
TI  - Characteristics and localization of rat submandibular gland proteoglycans.
AB  - The submandibular gland proteoglycans were investigated biochemically and
      immunohistochemically in male Sprague-Dawley rats. Proteoglycans were extracted
      with 4 M guanidine-HCl, followed by ultracentrifugation in a CsCl density
      gradient, and fractionated by ion-exchange chromatography and gel filtration. The
      molecular weight of PGs was estimated by SDS-PAGE and immunoblot analysis with
      monoclonal antibodies (HepSS-1 or 6-B-6). The glycosaminoglycan side-chains in
      the proteoglycan fractions were identified by electrophoresis on cellulose
      acetate membrane. Three proteoglycan fractions were obtained. One was a heparan
      sulphate proteoglycan that migrated as a diffuse band of about 210 kDa. The other
      two fractions contained at least two dermatan sulphate proteoglycans of 70-85 kDa
      and 40-50 kDa. Digestion of these two proteoglycans with chondroitinase ABC, but
      not heparitinase, produced two bands of 50 and 21 kDa, which were core proteins.
      The smaller dermatan sulphate proteoglycan may be a portion of the other, as the
      core protein of both bound to 6-B-6 antibody, and sugar chains of both were the
      same (20-30 kDa). Heparan sulphates recognized by antibody HepSS-1 were observed
      widely in the basement membrane, fibrous connective tissue, and striated and
      excretory ductal cells, while dermatan sulphate proteoglycans recognized by
      antibody 6-B-6 were located in the connective tissue surrounding striated and
      excretory ducts.

PMID- 9031704
TI  - Stoichiometry of oxygen consumption and sugar, organic acid and amino acid
      utilization in salivary sediment and pure cultures of oral bacteria.
AB  - In each of 23 numerically or metabolically significant oral micro-organisms, and
      in each of the salivary sediments of 10 humans, oxygen uptake was determined
      quantitatively with various sugar and organic and amino acid substrates. With
      relatively few exceptions, the salivary sediments rapidly consumed oxygen with
      the array of substrates (23) tested. On the other hand, the individual pure
      cultures oxidized fewer substrates and did so selectively from this menu. The
      observation that the Gram-positive bacteria readily used oxygen when sugar
      substrates were provided, but were unable to use oxygen with all but one of the
      organic and none of the amino acids was significant. The Gram-negative bacteria,
      in contrast, used oxygen poorly with the sugars but most readily with many of the
      organic and amino acids, was significant. Only two of the Gram-positive but most
      of the Gram-negative micro-organisms tested showed oxygen uptake with L(+)
      lactate; the Gram-negative bacteria were also active with D(-)-lactate, formate
      and succinate. Propionate was also tested and showed oxygen uptake only with the
      Gram-negative micro-organism, Neisseria subflava; acetate showed none or almost
      none with all of the examined bacteria. Where oxygen consumption occurred with
      the various pure or mixed cultures and substrates tested, the quantities of
      oxygen consumed were less than theoretically possible. For example, they ranged
      on average in the sediment results from 1.78 mumol oxygen per mumol of L(+)
      lactate catabolized to 5.17 mumol oxygen per mumol of lactose. This was
      consistent with substrate oxidation by the oral bacteria being less than complete
      as in aerobic glycolysis, and with compounds other than water and carbon dioxide
      (such as acetate) being prominent amongst the end-products produced. The pure
      culture oxygen data and other reports from this laboratory have made it possible
      to propose a speculative scheme as to which bacterial species might be involved
      in the various metabolic pathways used when different substrates are catabolized
      and oxidized by the mixed bacteria in salivary sediment or dental plaque. Also,
      it made it possible to suggest which bacteria and substrates are likely to be
      involved in the oxygen depletion that enables plaque to achieve anaerobiosis.

PMID- 9031705
TI  - Polymerase chain reaction analysis of oestrogen and androgen receptor expression
      in human gingival and periodontal tissue.
AB  - Oestrogen and androgen receptors mediate the effects of their respective hormones
      by acting as ligand-activated transcription factors that control a wide range of
      biological processes. In order to determine whether periodontal and gingival
      tissues could respond to oestrogen and androgen, the specific and highly
      sensitive reverse-transcribed polymerase chain reaction (PT-PCR) was used to
      examine the presence of the mRNAs corresponding to these receptors. Expression of
      the androgen receptor was readily detected in periodontal and gingival tissue and
      in fibroblasts derived from these tissues, but transcripts for the oestrogen
      receptor were not detected in these samples. Moreover, treatment of the cultured
      fibroblasts with the oestrogen diethylstilbesterol (DES) or the androgen
      dihydrotestosterone (DHT) did not induce the expression of the oestrogen receptor
      mRNA; nor did the hormones modify the activity of the androgen receptor gene.
      These results suggest that, while periodontal and gingival tissues are not able
      to respond directly to oestrogen, they may nevertheless be highly sensitive to
      the anabolic effects of androgens.

PMID- 9031706
TI  - Angiogenic induction and cell migration in an orthopaedically expanded maxillary
      suture in the rat.
AB  - The purpose was to examine the effect of an angiogenic factor on cell migration
      patterns and osteoblast histogenesis during the 96 h following orthopaedic
      expansion of the anterior maxillary suture. Fifty rats were divided into four
      groups: (1) a control group that received only angiogenic induction via injection
      of 5 ng/g body wt recombinant human endothelial-cell growth factor; (2) an
      experimental group that received orthopaedic expansion and angiogenic induction;
      (3) a sham group that received orthopaedic expansion and normal saline injection;
      and (4) a baseline group that received no expansion or injection. The
      experimental and sham groups were subdivided to conduct experiments over 1, 2, 3
      or 4 days. The anterior portion of each maxilla was dissected free and
      demineralized. Sections (4 microns thick) were cut from every block and stained
      with Mayer's haematoxylin and eosin. Cell migration was analysed using a
      previously established cell-kinetics model. The osteoprogenitor cells were
      divided into four categories according to nuclear volume: A cells (40-79
      microns3), B cells (80-119 microns3), C cells (120-169 microns3) and D cells (>
      or = 169 microns3 A' cells are the portion of the A cell population that responds
      to osteogenic stimulus. As previously defined in periodontal ligament, the
      reciprocal association of a decreasing number of less differentiated (A + A)
      cells and an increasing number of C + D cells, as a function of distance from the
      nearest major blood vessel, was consistently found in all groups. This suggests a
      vascularly oriented gradient of progressively more differentiated osteoprogenitor
      cells. Also, A + A' cells were predominately located within 20 microns of the
      nearest major blood vessel whereas the C + D cells were found at a distance > 30
      microns from the nearest major blood vessel. These results suggest that the A'-
      >C shift occurs 20-30 microns from the nearest major blood vessel. In the
      angiogenic induction groups, the numbers of committed osteoprogenitors (A + A')
      were significantly higher than in the sham group at day 1. At day 3, the numbers
      of preosteoblasts (C + D) in angiogenic sutures were significantly higher than in
      the sham groups. This enhancement of preosteoblast population strongly suggests
      the possible role of activated pericytes in expanded sutures as a source of
      osteoprogenitor cells.

PMID- 9031707
TI  - The influence of attentional factors on short- and long-latency jaw reflexes in
      man.
AB  - Reflexes evoked by applying non-painful taps to an incisor tooth were recorded
      bilaterally from the jaw-closing masseter and temporal muscles of 21 humans. A
      series of inhibitory, excitatory, inhibitory and excitatory waves (the Q, R, S
      and T waves) appeared in full-wave rectified and averaged post-stimulus
      electromyograms. These reflex responses were affected by the participants' levels
      of attention. When they undertook mental exercises in the form of arithmetic
      calculations, increases in electro-myographic activity were found around the
      transitions between the Q and R and the S and T waves. These increases involved
      principally a shortening of the inhibitory Q and S waves. There was no
      significant difference between the occurrence of these effects in the QR and ST
      segments. However, the effects were seen more commonly when the reflexes were
      evoked by hard (7.4 mN.s) as opposed to soft (3.4 mN.s) taps. It is concluded
      that, in man, attentional factors can modulate both short- and long-latency jaw
      reflexes, particularly when these are evoked by higher-threshold afferent nerves.

PMID- 9031708
TI  - Streptococcus mutans major adhesion surface protein, P1 (I/II), does not
      contribute to attachment to valvular vegetations or to the development of
      endocarditis in a rat model.
AB  - Streptococcus mutans P1 antigen functions as an adhesion factor for binding to
      salivary pellicle on tooth surfaces. It induces increased antibody titres in
      patients with Strep. mutans endocarditis. A mutant of Strep. mutans deficient in
      the function of the gene (spa P) encoding the surface antigen P1, and its
      isogenic parental strain, were used in a rat endocarditis experiment. Absence of
      P1 did not decrease adhesion to vegetations determined l h after intravenous
      infection. The number of bacteria recovered from valvular vegetations after 48 h
      from animals with manifest endocarditis did not differ between the strains.
      Consequently, the Pl antigen appears to be unimportant both for adhesion and
      virulence in endocarditis caused by Strep. mutans.

PMID- 9031709
TI  - Alpha brainwave training and perception of time passing: preliminary findings.
AB  - The ability to generate alpha brainwaves has been associated with the self
      regulation of stress. It has been suggested that generation of these brainwaves,
      above what is to be expected in a normal 24-hour EEG, contributes to an expanded
      state of consciousness. This study attempted to test Newman's theory that
      expansion of consciousness could be observed in perception of time passing.
      Twenty female college students were randomly assigned to an alpha brainwave
      training or beta (mock) brainwave training group. Following ten 30-minute
      training sessions over a five-week period of time, each subject in each group was
      asked to produce ten randomly assigned time intervals. Mean scores were obtained
      for each of the ten intervals for each group. An analysis of variance with
      repeated measures was used to analyze the time interval perceptions of each
      group. According to results obtained, both main effects and interaction effects
      were highly significant (p < .0001). This study offers a beginning effort to
      examine the consciousness altering capability of alpha brainwave generation.

PMID- 9031710
TI  - The effects of breathing pattern training on ventilatory function in patients
      with COPD.
AB  - The purpose of this study was to assess the effects of a particular breathing
      pattern training (BPT) on forced expiratory volume during the first second (FEV1)
      and forced vital capacity (FVC) in patients with chronic obstructive pulmonary
      disease (COPD). The subjects adjusted each breath to a target breath displayed on
      a video screen, by using visual feedback. This target was chosen in an individual
      sample recorded at rest. We used a randomized, controlled group design. Twenty
      patients with stable COPD, FEV1 less than 1.5 liters, undergoing a traditional
      rehabilitation program were randomly assigned to the BPT group or to the control
      group. Each BPT subject underwent 30-35 training sessions spread out over four
      weeks, in addition to the traditional program. FEV1 and FVC were performed before
      and after this program. ANOVAs showed that FEV1 and FVC significantly improved in
      BPT subjects, with a mean percent increase of 22% and 19%, respectively.
      Corresponding changes in controls were not significant. This study showed short
      term increases in FEV1 and FVC in COPD patients practicing BPT in addition to
      respiratory rehabilitation, in comparison with controls. Further studies should
      incorporate outcome data to clarify the mechanisms and the duration of this
      effect.

PMID- 9031711
TI  - Treatment of a depressive disorder patient with EEG-driven photic stimulation.
AB  - This study examined the effects of electroencephalographic- (EEG-) driven photic
      stimulation on a case of depressive disorder, as measured by a psychometric test
      of mood states, EEG parameters, and several autonomic indices. The EEG-driven
      photic stimulation enhances the alpha rhythm of brain waves using photic signals,
      the brightness of which is modulated by a subject's own alpha rhythm. The patient
      was a 37-year-old businessman, who was treated for depression with medication
      during the 13 months prior to his first visit to our hospital. He underwent two
      sets of inpatient treatment sessions, comprising first 16 and then 18 treatment
      sessions. The treatments brought about the following changes: an improvement in
      general mood state, alpha rhythm increase, cardiac parasympathetic suppression,
      and increased skin conductance level. In addition, significant correlations
      between alpha rhythm increase and cardiac parasympathetic suppression or cardiac
      sympathetic predominance were observed with each inpatient treatment. Significant
      correlations between alpha rhythm increase, cardiac parasympathetic suppression,
      or cardiac sympathetic predominance and the improvement of general mood state
      were also observed. Thus, from these observations, it was concluded that the
      alpha enhancement induced by EEG-driven photic stimulation produced an
      improvement in the patient's depressive symptomatology connected with cardiac
      parasympathetic suppression and sympathetic predominance.

PMID- 9031712
TI  - Good news--bad press: applied psychophysiology in cardiovascular disorders.
AB  - Dysregulation in blood pressure control can occur as a result of psychological
      stress in either the hypertensive or hypotensive direction. Applied
      psychophysiological techniques incorporating biofeedback and relaxation have been
      shown to be efficacious in controlled studies of hypertensive patients.
      Electromyograph, thermal, skin conductance and direct blood pressure feedback
      have been utilized alone or in combination with relaxation, blood pressure
      monitoring, and medication. Prediction models are proposed to define what type of
      hypertensive is most likely to respond with significant blood pressure decrease.
      Neurocardiogenic syncope is a cardiovascular disorder which manifests itself as
      lightheadedness, dizziness, syncope, and often migraine-type headache.
      Preliminary indications suggest that biofeedback-assisted relaxation may also
      prove beneficial to patients with this syndrome.

PMID- 9031718
TI  - Preparation of cross-linked hyaluronic acid films of low water content.
AB  - Hyaluronic acid (HA) was chemically cross-linked with poly(ethylene glycol)
      diglycidyl ether, a diepoxy compound (EX-810), to yield low water content and
      slowly degradable films when brought into contact with water. The cross-linking
      reaction was performed under acidic and neutral conditions, since the epoxy group
      is readily hydrolysed in alkaline media. To allow the reaction to proceed at high
      HA concentrations, a solution casting method was employed for the cross-linking
      of HA. The lowest water content of the cross-linked HA films obtained was 60 wt%
      when swollen with buffered saline at 37 degrees C. Alginic acid and poly(vinyl
      alcohol), which possess hydroxyl groups, similar to HA, were also found to
      undergo cross-linking with the diepoxy compound. Since IR spectra of the cross
      linked films had no significantly new absorption, intermolecular formation of
      ether bonds between the hydroxyl groups belonging to different polysaccharide
      molecules was assumed to take place. It seemed too difficult to detect the ether
      bonds in the cross-linked HA films, because the virgin HA film itself contained
      ether bonds in the molecule. The cross-linked HA film with a water content of 60
      wt% exhibited practically no weight loss after 10 days of immersion in phosphate
      buffered saline (pH 7.4), while this film underwent in vivo degradation by 30%
      weight loss after 7 days of subcutaneous implantation in rats. The inflammation
      reaction elicited around the implanted film was not significant.

PMID- 9031719
TI  - Enhancement of cell growth on a porous membrane co-immobilized with cell-growth
      and cell adhesion factors.
AB  - Insulin was co-immobilized with cell adhesion factors such as fibronectin or
      polylysine on a porous poly(ethylene terephthalate) membrane. The surface of the
      poly(ethylene terephthalate) membrane was partially hydrolysed under alkaline
      conditions and the proteins were immobilized on the membrane surface using a
      water-soluble carbodiimide. The adhesion of STO mouse fibroblast cells onto the
      immobilized membrane was accelerated by the immobilization of fibronectin and
      polylysine. The cell growth was enhanced by immobilization of insulin. Co
      immobilization of insulin with the adhesion factors markedly accelerated cell
      growth. No significant differences were found between the effects of fibronectin
      and polylysine. The absence of insulin release was confirmed by the fact that
      growth was no accelerated under essentially the same culture conditions without
      direct contact with the protein-immobilized membrane.

PMID- 9031720
TI  - Mechanism of thrombin inhibition by antithrombin and heparin cofactor II in the
      presence of heparin.
AB  - The kinetics of thrombin inhibition by antithrombin (AT) and heparin cofactor II
      (HC II) were analysed as a function of the heparin concentration, from 10(-9) to
      10(-4) M. The initial concentrations of inhibitor (l) and thrombin (E) were set
      at equimolar levels (CI = CE = 10(-8) M). The experimental data indicate that the
      reaction of thrombin inhibition was second-order both in the absence and in the
      presence of heparin, and that the apparent rate constant increased at heparin
      concentrations ranging from 10(-9) to 10(-6) M and decreased at higher
      concentrations. The data fit with the kinetic model established by Jordan et al.
      [J. Biol. Chem. 1979, 254, 2902-2913] for the catalysis of the thrombin-AT
      reaction by a low-molecular-weight heparin fraction. In this model, heparin (H)
      binds quickly to the inhibitor (I) and forms a heparin-inhibitor complex (HI),
      which is more reactive than the free inhibitor towards thrombin, leading to the
      formation of an inactive inhibitor-thrombin complex (I*E) and the release of free
      heparin, in a second step which is rate limiting. KH,I, the dissociation constant
      of HI, and k, the second-order rate constant of free thrombin inhibition by HI,
      were found to be 3.7 x 10(-7) M and 1.3 x 10(9) M-1 min-1, respectively, for AT,
      compared to a KH,I of 2.0 x 10(-6) M and k of 6.4 x 10(9) M-1 min-1 for HC II.
      These data indicate that heparin-HC II complex reactivity is greater than that of
      the heparin-AT complex towards thrombin, whereas heparin affinity is stronger for
      AT. At heparin concentrations higher than 10(-6) M, the decrease in the reaction
      rate was in keeping with the formation of a heparin-thrombin complex (HE), whose
      inactivation by the heparin-inhibitor complex (HI) is slower than that of the
      free protease.

PMID- 9031721
TI  - Calcium phosphate as a gene carrier: electron microscopy.
AB  - Transfection of DNA into cultured cells by the calcium phosphate (CaPi)-mediated
      method provides a means of examining gene functions. Several factors in preparing
      the CaPi-DNA co-precipitates were speculated to be correlated with the
      transfection efficiency. To achieve a better understanding of the steps of CaPi
      formation and the effect of other components in the medium, this study was
      undertaken to examine the morphological changes of CaPi in the transfection
      medium. Transmission electron microscopy (TEM) was employed to investigate the
      reaction products of CaPi precipitates prepared in the presence or absence of
      plasmid DNA, Dulbecco's modified Eagle medium and calf serum. The effect of pH of
      the HEPES-buffered saline (HBS) in which CaPi was formed was also examined. Here
      we report the observations we obtained from TEM. The results showed that CaPi
      precipitates underwent several steps of conversion in the presence of other
      components in the cell culture medium. The pH of the HBS in which CaPi
      precipitates were formed also exerts a profound effect on the morphology of the
      CaPi solid phase, indicating that the associated compositional and structural
      changes occurred during the maturation of CaPi in the DNA transfection medium.

PMID- 9031722
TI  - Morphological and biomechanical difference in healing in segmental tibial defects
      implanted with Biocoral or tricalcium phosphate cylinders.
AB  - To evaluate the effects of two bioceramics on bone regeneration during repair of
      segmental bone defects, Biocoral and tricalcium phosphate cylinders were
      implanted in osteotomized sheep tibial defects 16 mm in length and followed up
      for 16 weeks. In comparison with the TCP-implanted defect, a significant
      increment in area and density of external callus was quantified
      radiomorphometrically at 3 weeks, and a marked increase in maximal torque
      capacity, maximal angle of deformation and absorption of energy was demonstrated
      mechanically in the Biocoral-implanted tibia at 16 weeks after implantation.
      Better bone integration with the substratum was microscopically observed in
      Biocoral cylinders. With good osteointegration and biomechanical-performance,
      Biocoral seems to be superior to TCP in repair of segmental defects in weight
      bearing limbs.

PMID- 9031723
TI  - Resorbable and non-resorbable augmentation devices for tenorrhaphy of xenografts
      in extensor tendon deficits: 12 week study.
AB  - Resorbable (poly-L-lactide) and non-resorbable (polyethylene terephathalate)
      tendon augmentation devices (TAD) in conjunction with a pericardial adhesion
      barrier, were designed to strengthen tenorrhaphies and were evaluated in an ovine
      extensor tendon deficit model in a short term study. Fifteen centimetres of
      tendon were resected and replaced with kangaroo tail tendon xenografts that had
      been cross-linked with 0.075% glutaraldehyde (GA) at 4 degrees C for one or seven
      days. Compared with tenorrhaphies performed with Kessler sutures alone, both
      types of TAD were more effective at preventing tenorrhaphy dehiscence, and thus
      maintaining tendon function. Furthermore, tensile strength of TAD tenorrhaphies
      increased significantly between zero and twelve weeks. For xenografts cross
      linked in GA for one day, the tensile strength of tenorrhaphies with the
      resorbable TAD rose from 38 +/- 9 N at time zero, to 116 +/- 46 N at twelve
      weeks, while non-resorbable TAD tenorrhaphy strength at time zero was 42 +/- 16 N
      and 99 +/- 27 N at twelve weeks. For xenografts cross-linked with GA for seven
      days, similar increases in tensile strength of tenorrhaphies, with the two types
      of TAD were found. As there was no significant difference in mechanical
      performance or tissue response between the two TAD types in the first 12 weeks,
      use of the resorbable poly-L-lactide device may be advantageous clinically.
      Tensile strengths of midsections of the tendon xenograft cross-linked for 7 days
      was not significantly diminished 12 weeks after implantation and these xenografts
      were partially remodelled around the periphery. However, the tensile strength of
      xenografts cross-linked for one day declined significantly between time zero (319
      +/- 80 N) and twelve weeks (239 +/- 92 N), suggesting that this degree of cross
      linking was inadequate for maintenance of mechanical strength. Evaluation of the
      performance of tenorrhaphy augmentation devices with xenografts, over a longer
      implantation period, is required to further understand their usefulness for
      reconstruction of traumatic tendon injuries.

PMID- 9031724
TI  - Influence of fibrin sealant (Tisseel) on osteochondral defect repair in the
      rabbit knee.
AB  - Fibrin adhesives have been shown to improve the natural repair of musculoskeletal
      tissues. Growth hormone (GH) has a chondrogenic effect on immature cartilage. To
      test if a fibrin adhesive with and without GH could improve the natural repair of
      a joint surface lesion, we made a 9 x 4 mm2 osteochondral defect in the femoral
      groove of adult New Zealand rabbits. The defect in one of the knees was filled
      with the fibrin adhesive Tisseel, while the defect in the other knee was left
      untreated as a control. Another group of rabbits was treated in both knees with
      fibrin adhesive with local addition of GH during 1 week on one side. The
      experiments showed that the fibrin treatment impaired the natural repair of the
      osteochondral defect and that GH addition had no effect on the healing process.
      In a second in vitro experiment, chondrocyte migration into the fibrin adhesive
      Tisseel was compared to migration into rabbit and human blood clots. No cell
      migration was seen into the fibrin adhesive, while there was migration into the
      blood clots. We conclude that a fibrin adhesive like Tisseel is not suitable as a
      scaffold to promote repair of osteochondral defects in the rabbit knee.

PMID- 9031725
TI  - High-performance liquid chromatography assay of N,N-dimethyl-p-toluidine released
      from bone cements: evidence for toxicity.
AB  - Five commercially available bone cements were analysed by high-performance liquid
      chromatography for detecting the residual content of an accelerator, the amine
      N,N-dimethyl-p-toluidine (DMPT), after curing. It was found that the
      concentration of DMPT in aqueous extracts decreases with time, being almost
      absent 7 days after curing. Differences were noticed among the cements; residual
      DMPT is higher in cements prepared with higher content of the amine. It is
      verified that DMPT's toxic effect on cell cultures is dose-related; a delay in
      the cell replication cycle is induced in vitro. Damage is reversible, thus
      justifying the low bone cement toxicity that is clinically ascertained.

PMID- 9031726
TI  - Characterization of corrosion products on a copper-containing intrauterine device
      during storage at room temperature.
AB  - This paper studies the characterization of corrosion products formed on corroded
      and uncorroded copper-containing intrauterine devices stored at room temperature
      for a period of 30 months. The experimental techniques used were X-ray photo
      electron spectroscopy and Auger electron spectroscopy. The compounds found were
      cuprite (Cu2O) and tenorite (CuO). The latter was the main compound formed on
      corroded samples, forming thin tarnish films.

PMID- 9031727
TI  - Effect of thermal treatment on sterility, molecular and mechanical properties of
      various polylactides. 2. Poly(L/D-lactide) and poly(L/DL-lactide).
AB  - Pins for orthopaedic applications injection-moulded from as-supplied poly(L/D
      lactide) 95/5% and poly(L/DL-lactide) 95/5%, raw as-supplied polymers or raw
      methanol-extracted polymers were heat-treated for a predetermined time at 135
      degrees C under moisture-free argon. The sterility, molecular weight,
      polydispersity, mechanical properties, and crystallinity of the heat-treated
      samples were evaluated. All the samples heat treated under argon were sterile
      after 2 h exposure to heat. The heat-treated pins and raw as-supplied polymers
      showed a continuous decrease in molecular weight over the entire 50 h of heating,
      the decrease being more substantial for poly(L/D-lactide) than poly(L/DL
      lactide). Raw methanol-extracted polymers showed an increase of molecular weight
      after 2 h of heat treatment, followed by a gradual decrease of molecular weight
      up to 50 h. A drop in the bending strength, an increase in the bending moduli,
      and no change in the shear strength was observed for polylactide pins during the
      first 5 h of thermal treatment. For both the polymers, there was a progressive
      increase in crystallinity over time of thermal treatment, and practically no
      change in the melting temperature.

PMID- 9031728
TI  - Long-term in vivo degradation and bone reaction to various polylactides. 1. One
      year results.
AB  - Injection-moulded pins from poly(L-lactide), poly(L/DL-lactide) (95/5%) were
      implanted in the cortex of the tibiae of sheep. The bone-implant interface was
      evaluated to observe whether there is any bone resorption caused by the implants.
      The molecular weight and crystallinity changes upon implantation were also
      measured. There was no net bone loss around the implants or sterile cyst
      formation in any of the animals implanted with polylactides up to 1 year. The new
      bone formed around the poly(L-lactide) and poly(L/D-lactide) pins was separated
      from the implants with a thin layer of connective tissue. For the implants from
      poly(L/DL-lactide), there was direct apposition of bone on the polymeric
      material. At 1 year of implantation, the implants were not completely resorbed,
      although the molecular weight of polylactides was reduced from 40,000-50,000 to
      500-300. The crystallinity at 1 year was about 45% for poly(L/DL-lactide) and
      poly(L/DL-lactide) and 65% for poly(L-lactide), respectively, indicating the
      presence in the degraded material of thermodynamically stable crystals.

PMID- 9031729
TI  - Synthesis of poly(ethylene glycol)-silk fibroin conjugates and surface
      interaction between L-929 cells and the conjugates.
AB  - Poly(ethylene glycol) (PEG)-silk fibroin (SF) conjugates (PEG2-SF) were prepared
      by the chemical modification of solubilized SF with 2,4-bis[O
      methoxypoly(ethylene glycol)]-6-chloro-s-triazine (actPEG2) in borate buffer at
      37 degrees C. The IR spectra and DSC curves of PEG2-SF and SF suggested the
      introduction of PEG into SF by the modification and the beta-sheet structure of
      both SF and PEG2-SF induced by the treatment with methanol aqueous solutions. The
      content of the PEG component in PEG2-SF was evaluated to be 67% by weight from
      the melting enthalpy change of PEG observed on the DSC thermogram of PEG2-SF.
      Water content and contact angle measurements of SF before and after the
      modification indicated that the hydrophilicity of the PEG2-SF surface increased
      compared with that of SF. The attachment and growth of fibroblast cells (L-929)
      on the matrix of PEG2-SF were studied by a cell culture method. PEG2-SF exhibited
      very low cell attachment and growth, though SF exhibited high cell attachment and
      growth. The filopodium of the cells attached to PEG2-SF could not be found, and
      the cells aggregated to form masses in scanning electron microscopy images. These
      results could be explained in terms of the increased hydrophilicity of the PEG2
      SF surface.

PMID- 9031730
TI  - Effect of the alginate composition on the biocompatibility of alginate-polylysine
      microcapsules.
AB  - Alginate-polylysine (PLL) capsules are commonly applied for immunoprotection of
      endocrine tissues. Alginate is composed of mannuronic acid (M) and guluronic acid
      (G). Different types of alginate have different ratios of G to M, but little is
      known of the influence of these differences on biocompatibility. Therefore, we
      have investigated in vivo the effect of the G-content of the alginate on the
      biocompatibility of the capsules. Capsules prepared of commercially available
      alginates with either a high or an intermediate G-content were implanted in the
      peritoneal cavity of rats and retrieved one month later for histological
      evaluation. The fibrotic reaction was more severe against high-G alginate
      capsules than to intermediate-G alginate capsules. The majority of the high-G
      capsules proved to be overgrown and adherent to the abdominal organs whereas with
      intermediate-G alginate most capsules were found freely floating in the
      peritoneal cavity and free of any adhesion of cells. This was not caused by the
      alginate as such but rather by inadequate binding of high-G alginate to PLL since
      in the absence of PLL, i.e. with beads instead of capsules, no fibrotic reaction
      was observed. As high-G alginates have beneficial effects for islet
      encapsulation, efforts should be made to apply polycations which more effectively
      interact with high-G alginate than PLL.

PMID- 9031731
TI  - Development of bombesin-like and histamine-like innervation in the bullfrog (Rana
      catesbeiana) central nervous system.
AB  - Amphibians rely exclusively on behavioral thermoregulation to maintain body
      temperature within species- and developmental stage-specific critical limits.
      Several members of the bombesin family of peptides and histamine are included in
      a class of neurochemicals that have potent thermoregulatory effects in
      ectothermic and endothermic vertebrate species and may be involved in behavioral
      thermoregulation in amphibians. Because amphibians respond to environmental
      temperature cues differently in larval versus adult animals, we used
      immunocytochemistry to study developmental changes in bombesin-like (BN) and
      histamine-like (HA) innervation in the bullfrog brain and spinal cord. Neurons
      and fibers that were BN-immunoreactive and HA-immunoreactive were present in the
      earliest stage tadpoles examined (Gosner stage 29); BN-immunoreactive perikarya
      were found only in the preoptic area, posterior thalamic nucleus and in the
      rostroventral tegmentum of the mesencephalon. In the preoptic area, dramatic
      changes were observed in the number and staining intensity of BN-ir somata;
      neuronal labelling was greatest in tadpoles undergoing tail resorption (i.e.
      metamorphic climax) and was nearly absent in adults. Neurons immunoreactive to BN
      in the ventral mesencephalon also were developmental stage-dependent; limb-bud
      growth stage tadpoles had the largest numbers of labelled neurons, whereas in the
      adults, labelled cells were rarely visible in this area. The highest density of
      fibers was in the medial septum, lateral amygdala, and the optic tectum. Fewer
      fibers were observed within the dorsal and ventral hypothalamus, the pineal
      gland, and all the thalamic nuclei. Perikarya immunoreactive to HA were localized
      in the dorsal infundibular nucleus of the hypothalamus. Immunoreactivity was
      present in all developmental stages examined, and the numbers of labelled cells
      increased throughout metamorphosis to a maximum in adult brains. Fibers were
      found in the medial septum, medial amygdala, preoptic area, thalamus, pineal
      gland, hypothalamus and optic tectum. These results show that BN- and HA
      immunoreactivities are established early in larval development, but their
      phenotypes are differentially expressed during larval and adult growth stages.
      This pattern suggests that reorganization of BN-like and HA-like neural circuitry
      may occur during metamorphosis and may be involved in the reported developmental
      changes in amphibian thermoregulation. In addition, BN-like peptides and HA may
      modulate other related mechanisms of amphibian thermoregulation and behaviour,
      such as thermal acclimation, circadian shifts in temperature selection and
      feeding. To what extent they are involved in amphibian thermoregulation remains
      to be investigated.

PMID- 9031733
TI  - Distinct but overlapping populations of commissural and GABAergic neurons in the
      dorsal nucleus of the little skate, Raja erinacea.
AB  - In the little skate, Raja erinacea, the electrosensory primary afferents are
      responsive to electrical potentials created during the animal's own ventilation,
      while second-order electrosensory cells in the dorsal nucleus of the medulla
      suppress the responses to ventilatory potentials but retain their extreme
      sensitivity to important environmental electric signals. Previous
      electrophysiological studies indicate a role for a commissural pathway between
      the bilateral dorsal nuclei in ventilatory noise suppression. In the present
      study, retrograde tracers were used to label dorsal nucleus commissural cells.
      Large round or triangular and thin elongate commissural cells occur in the
      central zone of the dorsal nucleus where the primary afferent fibers terminate.
      Elongate commissural cells also occur in the peripheral zone which is the cell
      body area of the major efferents of the dorsal nucleus. Immunohistochemical
      studies indicate that stellate cells of the molecular layer and round or
      triangular cells of the central zone comprise the GABA-immunoreactive cell groups
      of the dorsal nucleus. A subpopulation of the round commissural cells in the
      central zone are GABA-immunoreactive and may be candidates for mediators of
      common-mode noise rejection in the dorsal nucleus of skates. The non-GABAergic
      commissural cells may mediate crossed inhibition through an inhibitory
      transmitter other than GABA or may supply crossed excitation to the dorsal
      nucleus.

PMID- 9031732
TI  - Avian homologues of mammalian intralaminar, mediodorsal and midline thalamic
      nuclei: immunohistochemical and hodological evidence.
AB  - This paper presents and reviews data suggesting that the dorsal thalamic zone
      (abbreviated DTZ) in birds is homologous to the intralaminar, midline, and
      mediodorsal thalamic nuclear complex (abbreviated IMMC) in mammals. The DTZ is
      located dorsomedially in the diencephalon of birds and consists of several
      subnuclei: nucleus dorsomedialis anterior thalami (DMA), nucleus dorsomedialis
      posterior thalami (DMP), nucleus dorsolateralis anterior thalami, pars medialis
      (DLM), nucleus dorsointermedius posterior thalami (DIP), nucleus dorsolateralis
      posterior thalami (DLP), and nucleus subhabenularis lateralis (SHL). Our
      immunohistochemical studies show that: (1) SHL and medial and dorsal parts of DMA
      and DMP are relatively rich in GABAergic, enkephalin-containing, substance P
      containing, and cholinergic fibers; (2) lateral parts of DMA and DMP are
      relatively poor in these neurotransmitters; and (3) DIP, DLP, and DLM are
      moderately rich in cholinergic and substance P-containing fibers. Our retrograde
      pathway tracing studies indicate that the DIP and DLP in the more lateral parts
      of DTZ project to somatic striatum, while the DMA, DMP, and SHL located more
      medially in the DTZ project to visceral/limbic striatum. Our anterograde tracing
      studies indicate that DIP receives afferents from the dorsal pallidum, whereas
      DMA and DMP appear to receive afferents from both the ventral striatum and
      ventral pallidum. Diverse prior studies have shown that in general medial and
      lateral components of DTZ are connected with visceral/ limbic and somatic brain
      regions, respectively. These characteristics indicate that: (1) SHL and medial
      and dorsal parts of DMA and DMP are comparable to mammalian midline thalamic
      nuclei, including the medial components of the intralaminar nuclei; (2) lateral
      parts of DMA and DMP are comparable to the mediodorsal nucleus in mammals; (3)
      DIP is comparable to the parafascicular nucleus in mammals; and (4) DLM and DLP
      are comparable to the laterally located intralaminar nuclei in mammals. The
      comparability of avian DTZ and mammalian IMMC suggests that they evolved from
      thalamic precursor nuclei present in the common reptilian ancestors and that they
      may perform similar roles in the movement control function of the basal ganglia.

PMID- 9031734
TI  - Relative hippocampal volume in relation to food-storing behavior in four species
      of woodpeckers.
AB  - Previous studies have shown that those food-storing birds of the order
      Passeriformes that remember the locations of their caches have relatively larger
      hippocampal complexes than do non-storing passerines. Woodpeckers constitute a
      different avian order (Piciformes), which also includes some food-storing
      species. We compared hippocampal volume, relative to the volume of the rest of
      the telencephalon, across four species of woodpeckers with disparate caching
      behavior. Red-bellied woodpeckers (Melanerpes carolinus) are "scatter hoarders'.
      During the fall and winter they cache acorns or beechnuts in dispersed sites
      throughout a large territory. Red-headed woodpeckers (Melanerpes erythrocephalus)
      also store nuts but in central "larders' on their small territories which they
      fiercely defend. Caching is absent or much reduced in hairy woodpeckers (Picoides
      villosus) and downy woodpeckers (Picoides pubescens), both of which forage on a
      variety of foods within large winter home ranges. The relative volume of the
      hippocampal complex in the scatter hoarder was larger than in the larder hoarder,
      suggesting that red-bellied woodpeckers, like passerine scatter hoarders, rely on
      memory to recover their caches. Surprisingly, the relative hippocampal volumes in
      the two non-storing Picoides woodpeckers were most similar to the scatter hoarder
      of the other genus. In passerine birds, hippocampal volume and telencephalon
      volume are highly correlated in storing species but not in non-storers. We found
      that the volumes of these two brain areas were highly correlated in both
      Melanerpes species, uncorrelated in the hairy woodpeckers, and more weakly
      correlated in the downy woodpeckers. The unexpectedly large hippocampal complexes
      in the Picoides species suggests they may engage in some behavior, other than
      food-storing, that selects for this trait. Conversely, our results concerning the
      relationship between hippocampal and telencephalon volumes may indicate that a
      weak correlation is associated with a less specialized hippocampus, independent
      of its relative volume.

PMID- 9031735
TI  - Volatile general anaesthetic actions on recombinant nACh alpha 7, 5-HT3 and
      chimeric nACh alpha 7-5-HT3 receptors expressed in Xenopus oocytes.
AB  - The effect of halothane and isoflurane was studied on the function of recombinant
      neurotransmitter receptors expressed in Xenopus oocytes. Both anaesthetics
      inhibited nicotinic acetylcholine type alpha 7 (nACh alpha 7) receptor-mediated
      responses, potentiated 5-hydroxytryptamine type 3 (5-HT3) receptor-mediated
      responses at low agonist concentrations, and inhibited the function of a chimeric
      receptor (with the N-terminal domain from the nACh alpha 7 receptor and the
      transmembrane and C-terminal domains from the 5-HT3 receptor) in a manner similar
      to that of the nACh alpha 7 receptor. Since the N-terminal domain of the chimeric
      receptor was from the nACh alpha 7 receptor, the observations suggest that the
      inhibition involves the N-terminal domain of the receptor.

PMID- 9031736
TI  - The inhibitory effects of mercaptoalkylguanidines on cyclo-oxygenase activity.
AB  - 1. It has been proposed that in inflammatory conditions, in which both the
      inducible isoforms of nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2)
      are induced, inhibition of NOS also results in inhibition of arachidonic acid
      metabolism. In the present study we have investigated whether
      mercaptoalkylguanidines, a novel class of selective iNOS inhibitors, may also
      influence the activity of cyclo-oxygenase (COX). Therefore, the effect of
      mercaptoethylguanidine (MEG) and related compounds on the activity of the
      constitutive (COX-1) and the inducible COX (COX-2) was investigated in cells and
      in purified enzymes. Aminoguanidine, NG-methyl-L-arginine (L-NMA) and NG-nitro-L
      arginine methyl ester (L-NAME) were also studied for comparative purposes. 2.
      Western blot analysis demonstrated a significant COX-1 activity in unstimulated
      J774 macrophages and in unstimulated human umbilical vein endothelial cells
      (HUVEC). Immunostimulation of the J774 macrophages by endotoxin
      (lipopolysaccharide of E. coli, LPS 10 micrograms ml-1) and interferon gamma (IFN
      gamma, 100 u ml-1) for 6 h resulted in a significant induction of COX-2, and a
      down-regulation of COX-1. No COX-2 immunoreactivity was detected in unstimulated
      HUVEC or unstimulated J774 cells. Therefore, in subsequent studies, the effect of
      mercaptoalkylguanidines on COX-1 activity was studied in HUVEC stimulated with
      arachidonic acid for 6 h, and in J774 cells stimulated with arachidonic acid for
      30 min. The effect of mercaptoalkylguanidines on COX-2 activity was studied in
      immunostimulated J774 macrophages, both on prostaglandin production by endogenous
      sources, and on prostaglandin production in response to exogenous arachidonic
      acid stimulation. In addition, the effect of mercaptoalkylguanidines on purified
      COX-1 and COX-2 activities was also studied. 3. In experiments designed to
      measure COX-1 activity in HUVEC, the cells were stimulated by arachidonic acid
      (15 microM) for 6 h. This treatment induced a significant production of 6-keto
      prostaglandin F1 alpha (6-keto-PGF1 alpha, the stable metabolite of
      prostacyclin), while nitrite production was undetectable by the Griess reaction.
      MEG (1 microM to 3 mM) caused a dose-dependent inhibition of the accumulation of
      6-keto-PGF1 alpha, with an IC50 of 20 microM. However, aminoguanidine, L-NAME or
      L-NMA (up to 3 mM) did not affect the production of 6-keto-PGF1 alpha in this
      experimental system. In experiments designed to measure COX-1 activity in J774.2
      macrophages, the cells were stimulated by arachidonic acid (15 microM) for 30
      min; this also induced a significant production of 6-keto-PGF1 alpha and MEG (1
      microM to 3 mM), aminoguanidine (at 1 and 3 mM), but neither L-NAME nor L-NMA
      inhibited the production of prostaglandins. 4. In experiments designed to measure
      prostaglandin production by COX-2 with endogenous arachidonic acid, J774.2 cells
      were immunostimulated for 6 h in the absence or presence of various inhibitors.
      In experiments designed to measure prostaglandin production by COX-2 with
      exogenous arachidonic acid, J774.2 cells were immunostimulated for 6 h, followed
      by a replacement of the culture medium with fresh medium containing arachidonic
      acid and various inhibitors. Both of these treatments induced a significant
      production of 6-keto-PGF1 alpha. Nitrite production, an indicator of NOS
      activity, was moderately increased after immunostimulation. MEG (1 microM to 3
      mM) caused a dose-dependent inhibition of the accumulation of COX metabolites.
      Similar inhibition of LPS-stimulated 6-keto PGF1 alpha production was shown by
      other mercaptoalkylguanidines (such as N-methyl-mercaptoethylguanidine, N,N'
      dimethyl-mercaptoethylguanidine, S-methyl-mercaptoethylguanidine and guanidino
      ethyldisulphide), with IC50 values ranging between 34-55 microM. However,
      aminoguanidine, L-NAME and L-NMA (up to 3 mM) did not affect the production of
      prostaglandins.5. In comparative experiments indomethacin, a non selective COX
      inhibitor, and NS-398, a selective COX-2 inhibitor, reduced (LPS) stimulated 6
      keto-PGF1alpha production in J774 macrophages in a dose-dependent manner without
      affecting nitrite release. Indomethacin, but not NS-398, inhibited 6-keto
      PGF1alpha production in the HUVECs. 6.The inhibitory effect of MEG was due to
      direct inhibition of the catalytic activity of COX as indicated in experiments
      with purified COX-1 and COX-2. MEG dose-dependently inhibited the purified COX-1
      and COX-2 activity with IC50 values of 33microM and 36microM, respectively.
      Aminoguanidine (at the highest concentrations) inhibited the formation of COX-1
      metabolites, without affecting COX-2 activity. High doses of L-NAME (3mM)
      decreased COX-1 activity only, while L-NMA (up to 3mM) had no effect on the
      activity of either enzyme. 7.These results suggest that MEG and related compounds
      are direct inhibitors of the constitutive and the inducible cyclo-oxygenases, in
      addition to their effects on the inducible NOS. The additional effect of
      mercaptoalkylguanidines on COX activity may contribute to the beneficial effects
      of these agents in inflammatory conditions where both iNOS and COX-2 are
      expressed.

PMID- 9031737
TI  - Effects of heptanol on electrical activity in the guinea-pig vas deferens.
AB  - 1. The effects of the putative intercellular uncoupling agent I-heptanol on
      electrical activity in the guinea-pig vas deferens were studied by use of
      intracellular and extracellular recording techniques. 2. At concentrations of
      0.5, 1 and 2 mM, heptanol rapidly, monotonically and reversibly attenuated
      intracellularly recorded excitatory junction potential (e.j.p.) amplitude without
      affecting its time course, while spontaneous excitatory junction potentials
      (s.e.j.ps) were left unaffected. 3. Heptanol did not affect either the
      extracellularly recorded evoked excitatory junction current (e.j.c.), or the
      nerve terminal impulse that preceded it. These observations indicate that
      heptanol does not affect nerve impulse conduction, neurotransmitter release, or
      the postjunctional receptors involved in the production of the e.j.p. 4. E.j.ps
      appear to be suppressed by heptanol due to its intercellular uncoupling effects.
      Therefore, functional intercellular coupling may be necessary for the generation
      of the e.j.p. in smooth muscle.

PMID- 9031738
TI  - Mechanism of contraction induced by bradykinin in the rabbit saphenous vein.
AB  - 1. By using fura-PE3 fluorometry and receptor-coupled permeabilization by alpha
      toxin, the mechanism of the bradykinin (BK)-induced contraction was determined in
      the rabbit saphenous vein (RSV). The receptor subtype responsible for the BK
      induced contraction of RSV was determined by means of a pharmacological blocker
      study and reverse transcription polymerase chain reaction (RT-PCR). 2. In the
      presence of extracellular Ca2+ (1.25 mM), BK (10(-11)-3 x 10(-7) M) induced
      increases in both the cytosolic Ca2+ concentration ([Ca2+]i) and force, in a
      concentration-dependent manner. Both the release of Ca2+ from the store site and
      the influx of extracellular Ca2+ contribute to an increase in [Ca2+]i induced by
      BK. 3. In the absence of extracellular Ca2+, the application of 10(-7) M BK
      induced transient elevations of [Ca2+]i and force, both of which thereafter
      declined to the levels observed before the application of BK. When extracellular
      Ca2+ was replenished (1.25 mM), [Ca2+]i and force increased to form a peak,
      followed by a sustained elevation in the presence of BK. When an RSV strip was
      pretreated with 10(-5) M thapsigargin for 20 min, the BK-induced transient
      increases in both [Ca2+]i and force were markedly inhibited. 4. These responses
      induced by BK were inhibited by Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]
      bradykinin), a highly specific bradykinin B2 receptor antagonist, in a
      concentration-dependent manner. In RT-PCR, B2-receptor mRNA was expressed in the
      smooth muscle of RSV. 5. The [Ca2+]i-force relationships, which were determined
      by cumulative applications of extracellular Ca2+ (0-5 mM) during 118 mM K(+)
      depolarization, shifted to the upper left in the presence of BK, thus indicating
      that BK induced a greater force than 118 mM K(+)-depolarization for a given level
      of [Ca2+]i. 6. In alpha-toxin-permeabilized preparations of RSV, application of
      10(-7) M BK after a steady state contraction had been induced by a mixture of 5 x
      10(-7) M Ca2+, 10(-6) M GTP and 10(-6) M captopril caused an additional force
      development at a constant [Ca2+]i. However, treatment with 1 mM guanosine-5'-O
      (beta-thiodiphosphate) (GDP beta S) for 5 min before and during the application
      of BK (10(-7) M), abolished this BK-induced additional contraction. 7. These
      results indicated that in RSV: (1) BK elicits vasoconstriction by increasing the
      Ca2+ influx from the extracellular space, Ca2+ release from intracellular
      thapsigargin-sensitive storage sites and increasing the Ca2+ sensitivity of the
      contractile apparatus, (2) the BK-induced increase in Ca2+ sensitivity is
      mediated by G-protein, (3) the BK-induced contractions are mediated via B2
      receptors and (4) the smooth muscle cells express B2-receptor mRNA.

PMID- 9031739
TI  - The effects of the peptide KPNFIRFamide (PF4) on the somatic muscle cells of the
      parasitic nematode Ascaris suum.
AB  - 1. Commonly used anthelmintic agents act on the muscle cells of parasitic
      nematodes to cause paralysis of the parasite and its expulsion from the host. 2.
      The motonervous system of nematodes contains neuropeptides, many of which are
      myoactive and elicit prolonged worm paralysis. Here we describe the actions of a
      novel peptide, KPNFIRFamide (Lys-Pro-Asn-Phe-Ileu-Arg-Phe-amide; PF4), which
      mediates relaxation of the somatic muscle of the parasitic nematode Ascaris suum.
      Its mechanism of action is compared to that of the inhibitory neuromuscular
      junction transmitter, gamma-aminobutyric acid (GABA), which gates a chloride
      channel on Ascaris muscle. 3. Both PF4 and GABA hyperpolarized the muscle cells
      (EC50 values 98 nM and 59 microM, respectively; n = 6) and this was accompanied
      by an increase in input conductance. 4. The increase in input conductance
      elicited by PF4 and a supramaximal concentration of GABA were additive (10 microM
      PF4, 7.78 +/- 1.88 microS; 10 mM GABA, 4.68 +/- 1.39 microS; 10 mM GABA and 10
      microM PF4 12.05 +/- 2.6 microS, n = 6, P < 0.02 with respect to PF4 alone; P <
      0.01 with respect to GABA alone). 5. The membrane potential response to 10 microM
      PF4 initially consisted of a fast hyperpolarization that occurred within 1 min of
      PF4 application. The reversal potential for this early response to PF4 (PF4
      early) was determined at different extracellular chloride concentrations. Linear
      regression analysis of the natural logarithm of the extracellular chloride
      concentration against the reversal potential for PF4-early yielded a straight
      line with a slope of -29.6 +/- 2.4 (-34.4 to -24.9, 95% confidence limits; r2 =
      0.82). This is close to the slope of -26.5 for a chloride-dependent event, as
      predicted by the Nernst equation. There was a significant correlation between the
      reversal potential for this event and the reversal potential for GABA (r = 0.94;
      P < 0.001; n = 12). 6. The late response to PF4 (PF4-late) appeared after 1 min
      and consisted of a slow reduction in the hyperpolarization to a plateau level,
      before the return of the membrane potential to the resting value. PF4-late is not
      likely to be a chloride-dependent event as during the hyperpolarization caused by
      a supramaximal concentration of GABA the muscle cells depolarized when a
      supramaximal concentration of PF4 was added to the perfusate. The membrane
      potential in the presence of 1 mM GABA was -61.8 +/- 4.8 mV and in the presence
      of 1 mM GABA with 10 microM PF4 was -47.5 +/- 1.5 mV (P < 0.02; n = 6). 7. The
      conductance increase elicited by 30 microM GABA was blocked by 10 microM
      ivermectin (before ivermectin 0.97 +/- 0.2 microS, after ivermectin 0.33 +/- 0.12
      microS; n = 5; P < 0.05; Student's paired t test) but the conductance increase
      elicited by 1 microM PF4 was not (before ivermectin 0.96 +/- 0.14 microS, after
      ivermectin 1.07 +/- 0.19 microS; n = 0.34; Student's paired t test). 8. These
      data indicate that PF4 elicits a potent, inhibition of Ascaris muscle cells which
      is partially mediated by chloride and which is independent of the inhibitory GABA
      receptor.

PMID- 9031741
TI  - Role of N-, P- and Q-type voltage-gated calcium channels in transmitter release
      from sympathetic neurones in the mouse isolated vas deferens.
AB  - 1. N-type voltage-gated calcium channels are known to play an important role in
      transmitter release from autonomic neurones, and recent studies have demonstrated
      that non-N-type calcium channels are also involved. The calcium channels coupled
      to transmitter release from sympathetic neurones in the mouse isolated vas
      deferens were investigated in the present study. 2. Contractions of the mouse vas
      deferens were evoked by electrical stimulation at 1-50 Hz. The contractions were
      entirely nerve-mediated, since they were abolished by tetrodotoxin, and were used
      as an indirect measure of transmitter release. 3. The N-type calcium channel
      blocker, omega-conotoxin GVIA, inhibited contractions in a concentration
      dependent manner, with a maximal effect at 30 nM. Contractions evoked by
      stimulation frequencies less than 10 Hz were abolished, and those evoked by 20
      and by 50 Hz stimulation were decreased in amplitude by 51.3 +/- 13.9% and 9.3 +/
      2.6%, respectively. 4. The N-, P- and Q-type channel blocker, omega-conotoxin
      MVIIC, inhibited contractions in a concentration-dependent manner and caused
      greater maximum inhibition than omega-conotoxin GVIA, suggesting an action on P-
      and/or Q-type channels, in addition to N-type. 5. The P-type channel blocker,
      omega-agatoxin IVA, alone did not have a significant effect at concentrations up
      to 300 nM, but inhibited contractions in the presence of omega-conotoxin GVIA.
      Subsequent addition of omega-conotoxin MVIIC abolished the remaining
      contractions. Identical results were obtained when the three toxins were tested
      cumulatively on the purinergic and noradrenergic components of the contraction in
      the presence of (1.3 microM prazosin and following desensitization to 10 microM
      alpha, beta-methylene adenosine 5'-triphosphate (alpha, beta-NeATP),
      respectively. 6. The results suggest that N-, P- and Q-type channels are involved
      in the release of noradrenaline and ATP from sympathetic neurones in the mouse
      vas deferens.

PMID- 9031740
TI  - In vivo receptor characterization of neuropeptide Y-induced effects in
      consecutive vascular sections of cat skeletal muscle.
AB  - 1. It has been suggested that the vasoconstrictor response to neuropeptide Y
      (NPY) is located in the microvessels and that it increases with reduced vessel
      diameter. The aim of the present study was to analyse quantitatively, on the cat
      gastrocnemius muscle preparation in vivo, the effects of NPY on total regional
      vascular resistance (RT) and its distribution to large-bore arterial resistance
      vessels (> 25 microns; Ra,prox), small arterioles (< 25 microns; Ra,micro) and
      the veins (Rv). Associated effects on capillary pressure (Pc,v) and fluid
      exchange were also studied. 2. Close-arterially infused NPY (1-32 micrograms kg-1
      min-1) caused a dose-dependent, slowly developing vasoconstriction in all three
      vascular sections, yet with a preferential action in the small arterioles. At 32
      micrograms kg-1 min-1, NPY raised RT by 133 +/- 22%, Ra,prox by 94 +/- 15%,
      Ra,micro by 277 +/- 104% and Rv by 81 +/- 11%. However, the veins (ED50 = 3.9 +/-
      1.2 micrograms kg-1 min-1) were more sensitive to NPY than both large-bore
      arterial vessels (ED50 = 7.7 +/- 1.6) and small arterioles (ED50 = 7.0 +/- 1.4).
      NPY decreased Pc,v due to an increase in the pre-to post-capillary resistance
      ratio. 3. Close-arterial infusions of Pro34NPY and peptide YY evoked
      vasoconstrictor responses which did not differ from the response to NPY. In
      contrast, the Y2-preferring C-terminal fragments: Ac-[Leu28, Leu31]-NPY (24-36)
      and NPY(13-36) were without effect in the muscle vascular bed. The selective NPY
      Y1 receptor antagonist BIBP3226 (100 micrograms kg-1 min-1, i.a.) abolished the
      vascular response to NPY. 4. The present findings indicate that the
      vasoconstrictor response to NPY in skeletal muscle is preferentially located in
      the small arterioles and mediated via the Y1 receptor and, further, that Y2 and
      Y3 receptors do not play a significant role in the vasoconstrictor response to
      NPY in cat skeletal muscle. BIBP3226 was found to be an effective NPY antagonist
      in vivo and to lack agonist activity.

PMID- 9031742
TI  - The antihypertensive effect of orally administered nifedipine-loaded
      nanoparticles in spontaneously hypertensive rats.
AB  - 1. The therapeutic use of nifedipine is limited by the rapidity of the onset of
      its action and its short biological half-life. In order to produce a form devoid
      of these disadvantages we made nanoparticles of nifedipine from three different
      polymers, poly-epsilon-caprolactone (PCL), polylactic and glycolic acid (1:1)
      copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene
      glycol 400 (PEG) solution was used as a control. 2. The average diameters of the
      nanoparticles ranged from 0.12 to 0.21 micron; the encapsulation ratio was 82% to
      88%. 3. In spontaneously hypertensive rats (SHR), the initial rapid fall in
      systolic arterial blood pressure following oral administration of nifedipine in
      PEG solution (from 193 +/- 3 to 102 +/- 2 mmHg) was not seen following
      administration of the same dose in Eudragit nanoparticles (from 189 +/- 2 to 156
      +/- 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure
      was significantly reduced (nadirs PCL 124 +/- 2 and PLAGA 113 +/- 2 mmHg). Ten
      hours following administration, blood pressure in rats administered the
      nifedipine/PEG preparation had returned to normal (183 +/- 3 mmHg) whereas that
      of animals given nifedipine in nanoparticles (PCL 170 +/- 3, PLAGA 168 +/- 2,
      Eudragit 160 +/- 3 mmHg) was still significantly reduced. 4. All of the
      nanoparticle dosage forms decreased Cmax and increased Tmax and the mean
      residence time (MRT) values. Relative bioavailability was significantly increased
      with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5. There was
      an inverse linear correlation between the fall in blood pressure and plasma
      nifedipine concentration with all preparations. 6. The nanoparticle nifedipine
      preparations represent sustained release forms with increased bioavailability, a
      less pronounced initial antihypertensive effect and a long-lasting action.

PMID- 9031743
TI  - Role of potassium channels and nitric oxide in the effects of iloprost and
      prostaglandin E1 on hypoxic vasoconstriction in the isolated perfused lung of the
      rat.
AB  - 1. The aims of this study were to compare in the rat isolated perfused lung
      preparation, the antagonist effects of iloprost, a stable analogue of
      prostacyclin, and prostaglandin E1 (PGE1) on the hypoxic pulmonary pressure
      response, and to investigate the possible involvement of KATP and KCa channels
      and of EDRF (NO) in the effects. In addition, iloprost and PGE1 effects were
      compared to those of adenosine and forskolin. 2. Isolated lungs from male Wistar
      rats (260-320 g) were ventilated with 21% O2 + 5% CO2 + 74% N2 (normoxia) or 5%
      CO2 + 95% N2 (hypoxia) and perfused with a salt solution supplemented with
      ficoll. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine
      methyl ester (L-NAME, 100 microM) were used to block KATP, KCa channels and NO
      synthesis, respectively. 3. Iloprost, PGE1, adenosine and forskolin caused
      relaxation during the hypoxic pressure response. The order of potency was:
      iloprost > PGE1 = forskolin > adenosine. EC50 values were 1.91 +/- 0.52 10(-9) M,
      3.31 +/- 0.58 10(-7) M, 3.24 +/- 0.78 10(-7) M and 7.70 +/- 1.68 10(-5) M,
      respectively. Glibenclamide, charybdotoxin and L-NAME inhibited partially the
      relaxant effects of iloprost and forskolin but not those of PGE1. 4. It is
      concluded that in the rat isolated lung preparation, iloprost and forskolin but
      not PGE1 dilate pulmonary vessels partly through KATP channels, KCa and nitric
      oxide release. Furthermore our results suggest that the role of cycli AMP in
      these effects is not unequivocal.

PMID- 9031744
TI  - Involvement of ATP in the non-adrenergic non-cholinergic inhibitory
      neurotransmission of lamb isolated coronary small arteries.
AB  - 1. The involvement of non-adrenergic non-cholinergic (NANC) transmitters, such as
      nitric oxide (NO) and adenosine 5'-triphosphate (ATP), in the neurogenic
      relaxation of lamb coronary small arteries was investigated in vessel segments
      with an internal lumen diameter of 200-550 microns, isolated from the left
      ventricle of the heart, and suspended for isometric tension recording in
      microvascular myographs. 2. In both endothelium-intact and -denuded coronary
      small arteries treated with phentolamine (3 x 10(-6) M), propranolol (3 x 10(-6)
      M), and atropine (10(-6) M) and contracted to 3 x 10(-7) M of the thromboxane
      analogue U46619, electrical field stimulation (EFS) evoked frequency-dependent
      relaxations, which were markedly reduced in the presence of tetrodotoxin (10(-6)
      M). 3. Exogenous NO added as acidified sodium nitrite (10(-6)-10(-3) M) and L
      nitrosocysteine induced potent relaxations of lamb coronary small arteries.
      However, both inhibition of NO synthase with NG- nitro-L-arginine (L-NOARG, 3 x
      10(-5) M), and mechanical endothelial cell removal increased rather than
      inhibited relaxations to EFS. In small arteries processed for NADPH-diaphorase
      histochemistry, activity was only observed within endothelial cells. 4. In
      arteries contracted to U46619, exogenously added ATP caused concentration
      dependent relaxations with pD2 and maximum responses of 4.72 +/- 0.12 and 89.6 +/
      3.8% (n = 12), respectively. ADP and the P2Y-agonist, 2-methylthio-ATP, induced
      relaxations equipotent to ATP, while the P2x-agonist, alpha, beta-methylene ATP
      (10(-9)-10(-4) M), and the P2U-agonist, UTP (10(-9)-10(-4) M) only caused small
      transient relaxations at the highest concentrations (10(-4) and 10(-3) M). 5. ATP
      and EFS-induced relaxations were unchanged in the presence of the P1-purinoceptor
      antagonist, 8-phenyltheophylline (10(-5) M), while this antagonist inhibited the
      concentration-dependent relaxations to adenosine. In contrast, the P2
      purinoceptor antagonist, suramin (3 x 10(-5) M), markedly reduced the relaxations
      to EFS. 6. After desensitization of P2x-purinoceptors with alpha, beta-methylene
      ATP (2 x 10(-5) M), the relaxations to exogenous added ATP were enhanced, but
      this procedure did not influence the relaxations to EFS. In contrast, the P2y
      purinoceptor antagonist, basilen blue E-3G (3 x 10(-5) M, earlier named reactive
      blue 2) significantly inhibited the concentration-relaxation curves to ATP and
      almost abolished the EFS-induced relaxations. 7. Mechanical removal of the
      endothelium significantly inhibited ATP-induced maximal relaxations without
      affecting sensitivity, pD2 and maximum relaxations being 4.72 +/- 0.12 and 89.7
      +/- 3.8% (n = 10), and 5.45 +/- 0.38 and 48.0 +/- 8.6% (P < 0.05, paired t test,
      n = 10) in endothelium-intact and -denuded coronary small arteries, respectively.
      However, incubation with L-NOARG did not change relaxations elicited by ATP. 8.
      The present study suggests that in NANC conditions neurogenic relaxations of
      coronary small arteries are mediated by ATP, which relaxes coronary small
      arteries through P2Y-purinoceptors. A prejunctional modulation of these
      relaxations by endothelial-derived NO cannot be excluded.

PMID- 9031745
TI  - The effect of the protein phosphatases inhibitor cantharidin on beta-adrenoceptor
      mediated vasorelaxation.
AB  - 1. Cantharidin, an inhibitor of protein phosphatase types 1 (PP1) and 2A (PP2A),
      increased basal tone of bovine isolated coronary artery rings (CARs) with and
      without endothelium in a time- and concentration-dependent manner with pEC50
      values of about 5.1 and 5.2, respectively, for both preparations. 2. Beta
      Adrenoceptor stimulation with isoprenaline (Iso; 0.03-100 microM) or inhibition
      of phosphodiesterase activity by 3-isobutyl-1-methylxanthine (IBMX; 10-1000
      microM), respectively, relaxed CARs precontracted with KCl (75 mM). CARs with and
      without endothelium showed no difference in the relaxing response to Iso and
      IBMX, respectively. 3. Cantharidin (3 microM) attenuated vasorelaxation induced
      by Iso (0.03-100 microM) in CARs with and without endothelium in a time-dependent
      manner, whereas vasorelaxation induced by IBMX (10-1000 microM) was not
      attenuated by 3 microM cantharidin. 4. Cantharidin (3 microM) did not affect
      cyclic AMP content in bovine cultured vascular cells, i.e. coronary artery smooth
      muscle cells (BCs), aortic endothelial cells (BAECs) and aortic smooth muscle
      cells (BASMCs), either under basal conditions, after beta-adrenoceptor
      stimulation (Iso) or inhibition of phosphodiesterase activity (IBMX),
      respectively. 5. Cantharidin inhibited protein phosphatase activity in
      homogenates from bovine coronary artery rings with a pIC50 of about 6.0. In
      homogenates of bovine cultured vascular cells pIC50 values of cantharidin
      amounted to about 6.5 for BCs, 6.7 for BAECs and 6.7 for BASMCs, respectively. 6.
      It was concluded that cantharidin differently affects vasorelaxation due to
      stimulation of beta-adrenoceptors (Iso) or inhibition of phosphodiesterase
      activity (IBMX), respectively. The attenuation of beta-adrenoceptor-mediated
      vasorelaxation by phosphatase inhibition is not due to diminished adenosine 3':5'
      cyclic monophosphate (cyclic AMP) generation but could be evidence for different
      subcellular compartments of cyclic AMP.

PMID- 9031746
TI  - Activation and inhibition of rat neuronal nicotinic receptors by ABT-418.
AB  - 1. ABT-418 appeared to function as a relatively broad spectrum activator of
      neuronal nicotinic receptors, expressed in Xenopus oocytes, with little cross
      reactivity to the mammalian muscle receptor subtype. However, the relative
      potencies of ABT-418 at the various subtypes differed from those acetylcholine
      (ACh). For example, ACh was most potent at alpha 3 beta 2 (EC50 approximately 30
      microM) and least potent at alpha 2 beta 2 (EC50 approximately 500 microM). ABT
      418 was most potent at alpha 4 beta 2 and alpha 2 beta 2 (EC50 approximately 6
      microM and 11 microM, respectively) and least potent at alpha 3 beta 4 (EC50
      approximately 188 microM). 2. In addition to activating neuronal receptors, ABT
      418 exhibited complex properties, including the inhibition of ACh responses. 3.
      The current responses elicited by relatively high concentrations of ABT-418 on
      the alpha 4 beta 2 receptor subtype were protracted beyond the application
      interval. The coapplication of ABT-418 with either of the use-dependent
      inhibitors bis(1,2,2,6,6-tetramethyl-4-pipendimyl)sebacate (BTMPS) or tetramethyl
      pipenidine (TMP) eliminated the late protracted phase of the currents with only
      small effects on the initial activation phase. When the reversible inhibitor TMP
      was washed from the bath, the previously inhibited late current reappeared,
      suggesting that the observed mixed agonist-antagonist effects of ABT-418 and (+/
      )-epibatidine on alpha 4 beta 2 were due to a concentration-dependent
      noncompetitive inhibition, an effect similar to that obtained for (-)-nicotine.
      4. The inhibition of alpha 4 beta 2 receptors by ABT-418 was voltage-dependent.
      When high concentrations of ABT-418 were applied under depolarizing conditions,
      additional late currents could be observed under conditions which suggested that
      a build up of ABT-418 in an unstirred layer over the surface of the oocyte was
      occurring. This may have been due to the dissociation of the drug from channel
      blocking sites on the receptors themselves, or alternatively, from the plasma
      membrane of the cells.

PMID- 9031747
TI  - Evidence against a role of cytochrome P450-derived arachidonic acid metabolites
      in endothelium-dependent hyperpolarization by acetylcholine in rat isolated
      mesenteric artery.
AB  - 1. In rat mesenteric artery, acetylcholine (ACh) causes endothelium-dependent
      hyperpolarization by releasing endothelium-derived hyperpolarizing factor (EDHF).
      Recent evidence suggests that EDHF may be a cytochrome P450-derived arachidonic
      acid metabolite. The aim of the present study was to investigate whether such a
      metabolite is indeed contributing to ACh-induced hyperpolarization observed in
      rat mesenteric artery. 2. The phospholipase A2 inhibitor quinacrine (30 microM)
      nearly completely eliminated ACh-induced hyperpolarization. However, the
      hyperpolarizing effect of pinacidil was also abolished in the presence of
      quinacrine. 3. The imidazole antimycotic agents ketoconazole (50 microM),
      clotrimazole (30 microM) and miconazole (10 microM), which bind to the heme
      moiety of cytochrome P450, eliminated not only ACh-induced hyperpolarizations but
      also those induced by pinacidil. SKF525A (30 microM), a prototype inhibitor of
      the enzyme, also abolished the hyperpolarizing responses to both agents. In
      contrast, neither 17-octadecynoic acid (10 microM), a mechanism-based inhibitor
      of cytochrome P450 metabolism of fatty acids, nor eicosatetraynoic acid (20
      microM), an inhibitor of all arachidonic acid metabolic pathways, altered ACh
      induced hyperpolarization. Furthermore, the hyperpolarization was unaffected by
      the preferential inhibitors of specific cytochrome P450 isozymes, alpha
      naphtoflavone (1 microM), diedthyldithiocarbamate (50 microM), metyrapone (20
      microM) and troleandomycin (10 microM). 4. Pretreatment of rats with
      lipopolysaccharide (2 mg kg-1) and exposure to nitroprusside (10 microM), both of
      which are expected to inhibit cytochrome P450 activity due to nitric oxide
      overproduction, were without effect on ACh-induced hyperpolarization.
      Pretreatment of rats for 3 days with pentobarbitone (80 mg kg-1 day-1), a
      cytochrome P450 inducer, also did not affect the hyperpolarizing response to ACh.
      5. Arachidonic acid in concentrations up to 100 microM had no detectable effect
      on smooth muscle membrane potential. 11, 12-Epoxyeicosatrienoic acid (EET, 10
      microM), one of cytochrome P450-derived epoxygenase metabolites of arachidonic
      acid, elicited a small endothelium-independent membrane hyperpolarization. The
      hyperpolarizing response to EET was blocked by glibenclamide (30 microM), in
      contrast to the response to ACh. 6. These results suggest that the contribution
      of a cytochrome P450-derived metabolite of arachidonic acid to ACh-induced
      hyperpolarization via EDHF release is minimal or absent in rat mesenteric artery.

PMID- 9031748
TI  - Pharmacological and biochemical evidence for the simultaneous expression of
      CCKB/gastrin and CCKA receptors in the pig pancreas.
AB  - 1. In the pig, the secretory response of the pancreas is not inhibited by the
      antagonist MK329 suggesting that cholecystokininA (CCKA) receptors are not
      involved. 2. Membranes were isolated from the pancreas of 6 Large White pigs to
      characterize their CCK receptors. 3. The binding of [125I]-BH-[Thr, Nle]CCK-9 was
      dependent on pH, maximal after a 90 min incubation period, saturable and
      reversible. Saturation analysis of the binding demonstrated a single class of
      high affinity sites (Kd = 0.22 +/- 0.02 nM) and a binding capacity, Bmax = 110.64
      +/- 12.50 fmol mg-1 protein. 4. Competition binding by agonists and antagonists
      of CCKA and CCKB/gastrin receptors demonstrated the presence of two distinct
      binding components, sites presenting a high affinity for [Thr, Nle]CCK-9,
      gastrin, PD 135158, L-365, 260 and a low affinity for MK329, SR 27897, and sites
      presenting a high affinity for [Thr, Nle]CCK-9, MK329, SR 27897 and a low
      affinity for gastrin, PD 135158, L-365,260. 5. These pharmacological data
      demonstrate the presence of both CCKA and CCKB/gastrin receptors in the pig
      pancreas, the latter being predominant. 6. Two distinct membrane proteins (50 and
      85-100 kDa, respectively) display pharmacological features of CCKB/gastrin and
      CCKA receptors. 7. In pigs, as in calves and humans, CCKB/gastrin receptors are
      predominant in the pancreas.

PMID- 9031749
TI  - Neuropeptide Y Y2 receptor and somatostatin sst2 receptor coupling to
      mobilization of intracellular calcium in SH-SY5Y human neuroblastoma cells.
AB  - 1. In this study we have investigated neuropeptide Y (NPY) and somatostatin
      (SRIF) receptor-mediated elevation of intracellular Ca2+ concentration ([Ca2+]i)
      in the human neuroblastoma cell line SH-SY5Y. 2. The Ca(2+)-sensitive dye fura 2
      was used to measure [Ca2+]i in confluent monolayers of SH-SY5Y cells. Neither NPY
      (30-100 nM) nor SRIF (100 nM) elevated [Ca2+]i when applied alone. However, when
      either NPY (300 pM-1 microM) or SRIF (300 pM-1 microM) was applied in the
      presence of the cholinoceptor agonist carbachol (1 microM or 100 microM) they
      evoked an elevation of [Ca2+]i above that caused by carbachol alone. 3. The
      elevation of [Ca2+]i by NPY was independent of the concentration of carbachol. In
      the presence of 1 microM or 100 microM carbachol NPY elevated [Ca2+]i with a
      pEC50 of 7.80 and 7.86 respectively. 4. In the presence of 1 microM carbachol the
      NPY Y2 selective agonist peptide YY(3-36) (PYY(3-36)) elevated [Ca2+]i with a
      pEC50 of 7.94, the NPY Y1 selective agonist [Leu31, Pro34]-NPY also elevated
      [Ca2+]i when applied in the presence of carbachol, but only at concentrations >
      300 nM. The rank order of potency, PYY(3-36) > or = NPY > > [Leu31, Pro34]-NPY
      indicates that an NPY Y2-like receptor is involved in the elevation of [Ca2+]i.
      5. In the presence of 1 microM carbachol, SRIF elevated [Ca2+]i with a pEC50 of
      8.24. The sst2 receptor-preferring analogue BIM-23027 (c[N-Me-Ala-Tyr-D-Trp-Lys
      Abu-Phe]) elevated [Ca2+]i with a pEC50 of 8.63, and the sst5-receptor preferring
      analogue L-362855 (c[Aha-Phe-Trp-D-Trp-Lys-Thr-Phe]) elevated [Ca2+]i with a
      pEC50 of approximately 6.1. Application of the sst3 receptor-preferring analogue
      BIM-23056 (D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2, 1 microM) to SH-SY5Y cells
      in the presence of carbachol neither elevated [Ca2+]i nor affected the elevations
      of [Ca2+]i caused by a subsequent coapplication of SRIF. The rank order of
      potency, BIM-23026 > or = SRIF > > L-362855 > > > BIM-23026 suggests that an sst2
      like receptor is involved in the elevation of [Ca2+]i. 6. Block of carbachol
      activation of muscarinic receptors with atropine (1 microM) abolished the
      elevation of [Ca2+]i by the SRIF and NPY. 7. Muscarinic receptor activation, not
      a rise in [Ca2+]i, was required to reveal the NPY or SRIF response. The Ca2+
      channel activator maitotoxin (2 ng ml-1) also elevated [Ca2+]i but subsequent
      application of either NPY or SRIF in the presence of maitotoxin caused no further
      changes in [Ca2+]i. 8. The elevations of [Ca2+]i by NPY and SRIF were abolished
      by pretreatment of the cells with pertussis toxin (200 ng-ml-1, 16 h). This
      treatment did not significantly affect the response of the cells to carbachol. 9.
      NPY and SRIF appeared to elevate [Ca2+]i by mobilizing Ca2+ from intracellular
      stores. Both NPY and SRIF continued to elevate [Ca2+]i when applied in nominally
      Ca(2+)-free external buffer. Thapsigargin (100 nM), an agent which discharges
      intracellular Ca2+ stores, also blocked the NPY and SRIF elevations of [Ca2+]i.
      10. Delta-Opioid receptor agonists applied in the presence of carbachol also
      elevate [Ca2+]i in SH-SY5Y cells. When NPY (30 nM) or SRIF (100 nM) was applied
      together with a maximally effective concentration of the delta-opioid receptor
      agonist DPDPE ([D-Pen2,5]-enkephalin) (1 microM), the resulting elevations of
      [Ca2+]i were not greater than those caused by application of DPDPE alone. 11.
      Thus, in SH-SY5Y cells, NPY and SRIF can mobilize Ca2+ from intracellular stores
      via activation of NPY Y2 and sst2-like receptors, respectively. Neither NPY nor
      SRIF elevated [Ca2+]i when applied alone. The requirements for the elevations of
      [Ca2+]i by NPY and SRIF are the same as those for delta- and mu-opioid receptor
      and nociceptin receptor mobilization of [Ca2+]i in SH-SY5Y cells.

PMID- 9031750
TI  - Effect of adrenergic and nitrergic blockade on experimental ileus in rats.
AB  - 1. In a rat model of experimental ileus, the effect of blockade of adrenergic and
      nitrergic neurotransmission was studied on the intestinal transit of Evans blue.
      2. Ether anaesthesia and skin incision had no influence on the transit.
      Laparotomy significantly inhibited the transit of Evans blue. This inhibition was
      even more pronounced when the small intestine was manipulated. 3. Reserpine (5 mg
      kg-1), a drug that blocks adrenergic neurotransmission, completely reversed the
      inhibition of the transit induced by laparotomy but only partially reversed that
      induced by laparotomy with manipulation of the small intestine. 4. N omega-nitro
      L-arginine (L-NOARG, 5 mg kg-1), a nitric oxide synthase inhibitor, completely
      reversed the reserpine-resistant inhibition induced by laparotomy with
      manipulation of the small intestine. The effect of L-NOARG was prevented by
      concomitant administration of L-arginine. L-Arginine itself slightly, but
      significantly enhanced the inhibition. S-methylisothiourea and aminoguanidine,
      selective inhibitors of the inducible NO synthase, had no effect on the transit
      after the three operations. 5. Treatment of the rats with reserpine plus L-NOARG
      had no additional effect on the transit after laparotomy as compared to reserpine
      alone. However, reserpine plus L-NNA completely reversed the inhibition of the
      transit induced by laparotomy with manipulation of the small intestine. 6. These
      findings support the involvement of adrenergic pathways in the pathogenesis of
      ileus and suggest that the additional inhibitory effect of mechanical stimulation
      results from an enhanced release of NO by the constitutive NO synthase.

PMID- 9031751
TI  - Functional GABAA receptors on rat vagal afferent neurones.
AB  - 1. In the present study, in vitro electrophysiology and receptor autoradiography
      were used to determine whether rat vagal afferent neurones possess gamma
      aminobutyric acid (GABA)A receptors. 2. GABA (1-100 microM) and isoguvacine (3
      100 microM) caused a concentration-dependent depolarization of the rat isolated
      nodose ganglion preparation at room temperature. When applied to the tissue 20
      min before the agonist, SR95531 (3 microM) and bicuculline (3 microM) caused a
      parallel shift to the right of the GABA and isoguvacine concentration-response
      curves, yielding shifts of 81 fold and 117 fold for SR95531 and 4 fold and 12
      fold for bicuculline, respectively. 3. Baclofen (10 nM-100 microM) was unable to
      elicit a depolarization of the rat isolated nodose ganglion preparation at either
      room temperature or at 36 degrees C, whilst 5-aminovaleric acid (10 microM), a
      GABAB receptor antagonist, was unable to antagonize significantly the GABA
      induced depolarization at either room temperature or at 36 degrees C. 4. [3H]
      SR95531 (7.2 nM), a GABAA receptor-selective antagonist, bound topographically to
      sections of rat brainstem. Specific binding was highest in the medial nucleus
      tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve (DMVN).
      Binding was also observed in certain medullary reticular nuclei, in particular
      the parvocellular reticular nucleus. 5. Unilateral nodose ganglionectomy caused a
      reduction in GABAA binding site density in the medial NTS from 93 +/- 7 to 68 +/-
      6 d.p.m./mm2. This procedure also caused a reduction in GABAA binding site
      density in the side of the NTS contralateral to the lesion, from 151 +/- 12 to 93
      +/- 7 d.p.m./mm2. Sham surgery had no effect on the binding of [3H]-SR95531 in
      rat brainstem. 6. The present data provide evidence for the presence of GABAA
      receptors located on the soma and central terminals of rat vagal afferent
      neurones. Additionally, a population of GABAA receptors is evidenced
      postsynaptically in the rat NTS with respect to vagal afferent terminals. These
      data are discussed in relation to the functional pharmacology of GABA in this
      region of the NTS.

PMID- 9031752
TI  - Pharmacological characterization of the sulphonylurea receptor in rat isolated
      aorta.
AB  - 1. The binding of the sulphonylurea [3H]-glibenclamide, a blocker of adenosine 5'
      triphosphate (ATP)-sensitive K+ channels (KATP channels), was studied in
      endothelium-denuded rings from rat aorta. 2. [3H]-glibenclamide labelled two
      classes of binding sites with KD values of 20 +/- 5 nM and 32 +/- 1 microM. The
      high affinity component, which comprised 17% of total binding at 1 nM [3H]
      glibenclamide, had an estimated binding capacity of 150 fmol mg-1 wet weight. 3.
      Other sulphonylureas such as glipizide and glibornuride and the sulphonylurea
      related carboxylate, AZ-DF 265, inhibited high affinity [3H]-glibenclamide
      binding with the potencies expected from their K+ channel activity. At very high
      concentrations, AZ-DF 265 and glipizide started to interact also with the low
      affinity component of [3H]-glibenclamide binding. 4. Openers of the ATP-sensitive
      K+ channel belonging to different structural groups inhibited only the high
      affinity [3H]-glibenclamide binding; the potencies in this assay were similar to
      those obtained in functional (i.e. vasorelaxation) studies. 5. High affinity [3H]
      glibenclamide binding was abolished by prolonged hypoxia combined with metabolic
      inhibition. 6. The data indicate that the high affinity component of [3H]
      glibenclamide binding mediates the block of the KATP channel by the
      sulphonylureas in rat aorta; hence, it represents the sulphonylurea receptor in
      this vessel. The pharmacological properties of this binding site resemble those
      of the binding site for the openers of the KATP channel; present evidence
      suggests that these two classes of sites are negatively allosterically coupled.

PMID- 9031753
TI  - Characterization of Y3 receptor-mediated synaptic inhibition by chimeric
      neuropeptide Y-peptide YY peptides in the rat brainstem.
AB  - 1. Neuropeptide Y (NPY) and peptide YY (PYY) act at receptors referred to as Y1
      and Y2, while the Y3 receptor is specific to NPY and does not recognize PYY. The
      effects of NPY, its related peptides and a series of newly constructed chimeric
      NPY-PYY peptides were examined on excitatory and inhibitory postsynaptic currents
      (e.p.s.cs and i.p.s.cs, respectively) in rat dorsomedial nucleus tractus
      solitarius (NTS) neurones recorded in coronal brainstem slices. Monosynaptic
      activity was evoked by electrical stimulation in the region of the tractus
      solitarius. 2. NPY (5-500 nM) inhibited e.p.s.cs and i.p.s.cs in a concentration
      dependent manner. In contrast, PYY (500 nM) failed to affect either e.p.s.cs or
      i.p.s.cs. The N- and C-terminal parts of a series of chimeric NPY-PYY peptides
      were joined at positions where NPY and PYY sequences differ. In binding
      experiments the chimeric peptides were all about equipotent with NPY and PYY in
      displacing [125I]-PYY from Y1 and Y2 binding sites on SK-N-MC cells and rat
      hippocampus respectively. 3. In the whole cell voltage clamp recordings of NTS
      neurones, NPY(1-23)-PYY(24-36) and NPY(1-14)-PYY(15-36) evoked a concentration
      dependent inhibition of e.p.s.cs and i.p.s.cs, while NPY(1-7)-PYY(8-36) and NPY(1
      3)-PYY(4-36) were inactive. The only differences in amino acid residues between
      NPY(1-14)-PYY(15-36) and NPY(1-7)-PYY(8-36) reside in positions 13 and 14. 4.
      Furthermore, [Pro34]NPY (500 nM) was equivalent in potency to NPY itself at
      inhibiting monosynaptic transmission in NTS, while [Leu31,Pro34]NPY and
      pancreatic polypeptide (both at 500 nM) failed to affect synaptic transmission.
      5. The present study has shown that NPY acts at Y3 receptors to suppress both
      excitatory and inhibitory currents in the NTS. The different efficacy of the
      chimeric NPY-PYY peptides suggests that positions 13 and 14 are of great
      importance for Y3 receptor recognition. Finally, this receptor type readily
      recognizes [Pro34]NPY, but not [Leu31,Pro34]NPY.

PMID- 9031754
TI  - In vitro and in vivo effects of UP 269-6, a new potent orally active nonpeptide
      angiotensin II receptor antagonist, on vascular smooth muscle cell proliferation.
AB  - 1. The present studies were designed to measure the affinity of UP 269-6, a newly
      developed angiotensin AT1 receptor antagonist, for vascular AT1 receptors from
      normotensive and hypertensive rats and to investigate in vitro, its effects on
      angiotensin II (AII)-induced hyperplasia and hypertrophy of vascular smooth
      muscle cells (VSMC). In addition the in vivo effects of UP 269-6 on neointimal
      proliferation in a carotid artery balloon injury in normotensive rats were also
      investigated. 2. UP 269-6 selectively inhibited [125I]-Sar1-Ile8-AII binding to
      vascular AT1 receptors present on VSMC derived from normotensive Wistar rat and
      from SHR (Ki = 16.6 +/- 3.6 nM and 7.5 +/- 2.0 nM, respectively). In comparison,
      losartan and its metabolite, EXP 3174, inhibited [125I]-Sar1-Ile8-AII binding to
      vascular AT1 receptors derived from both cell models with Ki values slightly
      lower (losartan) and higher (EXP 3174), respectively, than that of UP 269-6. 3.
      AII (1 microM) induced a weak and variable hyperplastic response (4 to 32%
      increase in cell number) in Wistar rat VSMC after 96 h. 4. AII (1 microM) induced
      a time-dependent increase in cell number in VSMC from SHR. UP 269-6 inhibited
      concentration-dependently this effect with an IC50 value of 159 +/- 58 nM.
      Losartan was clearly less potent and EXP 3174 showed nearly the same inhibitory
      potency, compared to UP 269-6. UP 269-6 (1 microM) inhibited nearly completely
      the action of AII. 5. AII (500 nM) caused maximal stimulation of protein
      synthesis in Wistar rat VSMC (117 +/- 36%). UP 269-6, losartan and EXP 3174
      totally inhibited this stimulation with IC50 values of 28 +/- 6 nM, 3504 +/- 892
      nM and 21 +/- 3 nM, respectively. 6. AII (50 nM) induced maximal stimulation of
      protein synthesis in SHR VSMC (237 +/- 67%). UP 269-6, losartan and EXP 3174
      totally inhibited this stimulation with IC50 values of 16 +/- 3 nM, 282 +/- 122
      nM and 3.3 +/- 1.0 nM, respectively. 7. UP 269-6 (75 mg kg-1 day-1) administered
      orally in the diet for 20 days induced a 38% reduction in neointimal area and a
      36% reduction in neointima/media ratio associated with the intimal thickening
      induced by carotid artery balloon injury. 8. In conclusion, UP 269-6 was shown to
      be a potent antiproliferative agent both in vitro on AII-induced hyperplasia and
      hypertrophy of VSMC derived from normotensive and hypertensive rats, and in vivo
      upon intimal thickening induced by carotid artery balloon injury in the rat.

PMID- 9031755
TI  - Mechanisms involved in the effect of nitric oxide synthase inhibition on L
      arginine-induced insulin secretion.
AB  - 1. A constitutive nitric oxide synthase (NOSc) pathway negatively controls L
      arginine-stimulated insulin release by pancreatic beta cells. We investigated the
      effect of glucose on this mechanism and whether it could be accounted for by
      nitric oxide production. 2. NOSc was inhibited by N omega-nitro-L-arginine methyl
      ester (L-NAME), and sodium nitroprusside (SNP) was used as a palliative NO donor
      to test whether the effects of L-NAME resulted from decreased NO production. 3.
      In the rat isolated perfused pancreas, L-NAME (5 mM) strongly potentiated L
      arginine (5 mM)-induced insulin secretion at 5 mM glucose, but L-arginine and L
      NAME exerted only additive effects at 8.3 mM glucose. At 11 mM glucose, L-NAME
      significantly inhibited L-arginine-induced insulin secretion. Similar data were
      obtained in rat isolated islets. 4. At high concentrations (3 and 300 microM),
      SNP increased the potentiation of arginine-induced insulin output by L-NAME, but
      not at lower concentrations (3 or 30 nM). 5. L-Arginine (5 mM) and L-ornithine (5
      mM) in the presence of 5 mM glucose induced monophasic beta cell responses which
      were both significantly reduced by SNP at 3 nM but not at 30 nM; in contrast, the
      L-ornithine effect was significantly increased by SNP at 3 microM. 6.
      Simultaneous treatment with L-ornithine and L-arginine provoked a biphasic
      insulin response. 7. At 5 mM glucose, L-NAME (5 mM) did not affect the L
      ornithine secretory effect, but the amino acid strongly potentiated the
      alteration by L-NAME of L-arginine-induced insulin secretion. 8. L-Citrulline (5
      mM) significantly reduced the second phase of the insulin response to L-NAME (5
      mM) + L-arginine (5 mM) and to L-NAME + L-arginine + SNP 3 microM. 9. The
      intermediate in NO biosynthesis, NG-hydroxy-L-arginine (150-300 microM) strongly
      counteracted the potentiation by L-NAME of the secretory effect of L-arginine at
      5 mM glucose. 10. We conclude that the potentiation of L-arginine-induced insulin
      secretion resulting from the blockade of NOSc activity in the presence of a basal
      glucose concentration (1) is strongly modulated by higher glucose concentrations,
      (2) is not due to decreased NO production but (3) is probably accounted for by
      decreased levels of NG-hydroxy-L-arginine or L-citrulline, resulting in the
      attenuation of an inhibitory effect on arginase activity.

PMID- 9031756
TI  - The role of B1 and B2 kinin receptors in oedema formation after long-term
      treatment with Mycobacterium bovis bacillus Calmette-Guerin (BCG).
AB  - 1. The present study was designed to investigate the influence of long-term
      systemic treatment with Mycobacterium bovis bacillus Calmette-Guerin (BCG, 1 dose
      per animal, containing 6 x 10(4) colony-forming-units (CFu), 5 to 75 days
      beforehand) on oedema formation induced by intradermal injection of B1 and B2
      selective agonists. The interaction between the B1 agonist des-Arg9-bradykinin
      and bradykinin was also investigated. 2. Intradermal injection (i.d.) of the B2
      selective agonist tyrosine8-bradykinin (1-10 nmol) in naive (saline pretreated)
      animals, or in animals that had received BCG (30 days beforehand), caused dose
      related and very similar oedema formation (ED50; 1.1 and 1.0 nmol/paw,
      respectively). I.d. injection of the selective B1 agonists des-Arg9-bradykinin
      (100 nmol) or des-Arg10-kallidin in naive animals caused very little paw oedema
      (0.04 +/- 0.06 and 0.07 +/- 0.02 ml, respectively, n = 5). However, i.d.
      injection of des-Arg9-bradykinin (10-300 nmol) or des-Arg10-kallidin (3-100 nmol)
      in animals pretreated with BCG, 30 days previously, resulted in dose-related and
      marked oedema formation, with mean ED50 values of 20.1 and 5.5 nmol/paw,
      respectively. 3. Oedema caused by i.d. injection of des-Arg9-bradykinin (100
      nmol/paw) in rats pretreated with BCG was evident 5 days after treatment,
      reaching the maximum 30 days later, remaining stable for up to 45 days, and
      reduced markedly at 75 days. 4. The i.d. co-injection of the selective B1
      antagonists des-Arg9[Leu8]-bradykinin (200 nmol), des-Arg10[Leu9]-bradykinin (30
      nmol) and des-Arg9-NPC 17731 (30 nmol) significantly (18 +/- 3, 34 +/- 2 and 56
      +/- 4%, respectively) prevented the paw oedema caused by i.d. injection of des
      Arg9-bradykinin (100 nmol) in rats treated with BCG. These effects were
      selective, because the i.d. injection of the B1 selective antagonist des
      Arg10[Leu9]-kallidin (30 nmol), at the same dose that consistently antagonized
      des-Arg9-bradykinin (100 nmol)-mediated paw oedema, had no significant effect
      against tyrosine8-bradykinin (3 nmol)-induced oedema in animals that had been
      treated previously with BCG. On the other hand, the i.d. co-injection of the
      selective B2 antagonist, Hoe 140 (10 nmol) at a dose which markedly inhibited
      tyrosine8-bradykinin (3 nmol)-induced oedema by 55 +/- 4%, did not significantly
      affect des-Arg9-bradykinin-induced paw oedema in animals pretreated with BCG. 5.
      Treatment of animals with dexamethasone (0.5 mg kg-1, s.c.) every 24 h, from day
      0 to day 30, inhibited significantly (67 +/- 4%) the oedema caused by des-Arg9
      bradykinin (100 nmol), but did not affect the paw oedema caused by tyrosine8
      bradykinin (3 nmol) in animals pretreated with BCG. 6. Indomethacin (2 mg kg-1,
      i.p.), administered 1 h before experiments, significantly inhibited des-Arg9
      bradykinin (100 nmol)-induced oedema formation, and, to a lesser extent, the paw
      oedema caused by tyrosine8-bradykinin (3 nmol) (44 +/- 4 and 20 +/- 4%,
      respectively). 7. These findings show that the long-term systemic treatment of
      rats with BCG promoted a time-dependent and consistent paw oedema formation to B1
      agonists, des-Arg9-bradykinin and des-Arg10-kallidin, leaving responses to the B2
      agonist tyrosine8-bradykinin unaffected. The upregulation of B1 receptors after
      BCG treatment was inhibited by dexamethasone, suggesting the possible involvement
      of de novo protein synthesis. Finally, our results also show that in BCG-treated
      animals, the B1 agonist des-Arg9-bradykinin interacts in a synergistic manner
      with bradykinin. Therefore, both B1 and B2 kinin receptors appear to play a
      relevant role in modulating chronic inflammatory processes.

PMID- 9031757
TI  - Identification of 5-hydroxytryptamine receptors positively coupled to adenylyl
      cyclase in rat cultured astrocytes.
AB  - 1. 5-Hydroxytryptamine (5-HT) elicited a dose-dependent stimulation of
      intracellular adenosine 3': 5'-cyclic monophosphate (cyclic AMP) accumulation in
      cultured astrocytes derived from neonatal rat (Sprague Dawley)
      thalamic/hypothalamic area with a potency (pEC50) of 6.68 +/- 0.08 (mean +/- s.e.
      mean). 2. In order to characterize the 5-HT receptor responsible for the cyclic
      AMP accumulation the effects of a variety of compounds were investigated on basal
      cyclic AMP levels (agonists) and 5-carboxamidotryptamine (5-CT) stimulated cyclic
      AMP levels (antagonists). The rank order of potency for the agonists investigated
      was 5-CT (pEC50 = 7.81 +/- 0.09) > 5-methoxytryptamine (5-MeOT) (pEC50 = 6.86 +/-
      0.36) > 5-HT (pEC50 = 6.68 +/- 0.08). The following compounds, at concentrations
      up to 10 microM, did not affect basal cyclic AMP levels 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT), cisapride, sumatriptan, DOI and RU 24969. The
      rank order of potency of antagonists was methiothepin (pKi = 7.98 +/- 0.25) >
      mesulergine (pKi = 7.58 +/- 0.18) > ritanserin (pKi = 7.20 +/- 0.24) > clozapine
      (pKi = 7.03 +/- 0.19) > mianserin (pKi = 6.41 +/- 0.19). The following compounds,
      at concentrations up to 10 microM, were inactive: ketanserin, WAY100635,
      GR127935. This pharmacological profile is consistent with that of 5-HT7 receptor
      subtype-mediated effects. 3. The cultured astrocytes exhibited regional
      heterogeneity in the magnitude of cyclic AMP accumulation (Emax). Cells cultured
      from the thalamic/hypothalamic area had significantly higher Emax values (588 +/-
      75% and 572 +/- 63% of basal levels for 5-CT and 5-HT, respectively) compared to
      brainstem (274 +/- 51% and 318 +/- 46%, respectively) and colliculus astrocytes
      (244 +/- 15% and 301 +/- 24%, respectively). No significant differences in pEC50
      (for either 5-HT or 5-CT) values were observed. 4. Reverse transcriptase
      polymerase chain reaction (RT-PCR) with primers specific for the 5-HT7 receptor
      confirmed expression of messenger RNA for this receptor subtype by the cultured
      astrocytes derived from all regions investigated. Primers specific for the 5-HT6
      receptor also amplified a cDNA fragment from the same samples. 5. From these
      findings, we conclude that astrocytes cultured from a number of brain regions
      express functional 5-HT receptors positively coupled to adenylyl cyclase and that
      the level of receptor expression or the efficiency of receptor coupling is
      regionally-dependent. The pharmacological profile of the receptor on
      thalamic/hypothalamic astrocytes suggests that the 5-HT7 receptor is the dominant
      receptor that is functionally expressed even though astrocyte cultures have the
      capacity to express both 5-HT6 and 5-HT7 receptor messenger RNA.

PMID- 9031758
TI  - Inhibitory effects of TAK-044 on endothelin induced vasoconstriction in various
      canine arteries and porcine coronary arteries: a comparison with selective ETA
      and ETB receptor antagonists.
AB  - 1. The inhibitory effects of the endothelin (ET) receptor antagonist, TAK-044, on
      ET-induced vasoconstriction in various canine arteries and porcine coronary
      arteries were studied and were compared to those of selective ETA and ETB
      receptor antagonists. 2. ET-1 (0.1 nM-0.3 microM) caused vasoconstriction in
      canine coronary, femoral, renal, mesenteric and basilar arteries, and the
      strongest responses were obtained in coronary and basilar arteries. TAK-044 (10
      nM, 100 nM) inhibited this ET-1-induced vasoconstriction except in the case of
      mesenteric arteries. The strongest inhibitory effects were obtained in coronary
      arteries; an EC50 value for ET-1 was 5.2 +/- 0.77 nM (n = 12) in the control and
      24 +/- 3.8 nM (n = 4) in the presence of TAK-044 at 10 nM. BQ-123 (1 microM)
      inhibited the vasoconstriction in coronary and femoral arteries but did not in
      renal, mesenteric or basilar arteries. 3. TAK-044 (10-100 nM) inhibited the ET-1
      induced vasoconstriction in porcine coronary arteries to a degree similar to that
      in canine coronary arteries. In contrast, BQ-123 (10 microM) did not inhibit the
      contraction completely, and a BQ-123-insensitive component was identified.
      Although BQ-788 (1 microM) did not modify the concentration-response curve at
      all, it abolished the BQ-123-insensitive component when applied together with BQ
      123 (10 microM). 4. Sarafotoxin S6c (10 pM-30 nM) caused vasoconstriction in
      porcine coronary arteries with the maximum amplitude of the contraction being 39%
      of that with ET-1. Both TAK-044 (10 nM, 100 nM) and BQ-788 (1 microM) inhibited
      this vasoconstriction, while BQ-123 (3 microM, 10 microM) did not. 5.
      Vasoconstriction induced by ET-3 (0.1 nM-0.3 microM) in porcine coronary arteries
      showed a concentration-response curve with two distinct phases in contrast to
      that seen with sarafotoxin S6c. TAK-044 (0.3 nM-10 nM) inhibited both phases in a
      concentration-dependent manner. BQ-123 (1 microM, 3 microM) inhibited only the
      second phase, while BQ-788 (1 microM) inhibited the first phase. 6. We concluded
      that the inhibitory effects of TAK-044 on ET-1-induced vasoconstriction were the
      strongest in coronary arteries among the canine arteries examined. In addition,
      we showed that both ETA and ETB receptors mediate vasoconstriction in porcine
      coronary arteries and TAK-044 inhibits the vasoconstriction mediated by both of
      these receptors.

PMID- 9031759
TI  - Ischaemia-induced loss or reversal of the effects of the class I antiarrhythmic
      drugs on vulnerability to fibrillation.
AB  - 1. In the last decade, a number of clinical observations have questioned the
      efficacy of certain class I antiarrhythmic drugs against ischaemia-induced
      ventricular fibrillation. The effects of three drugs of this class, disopyramide
      (Ia), lignocaine (Ib) and flecainide (Ic) on the vulnerability to fibrillation
      during experimental ischaemia were investigated. 2. The study was carried out in
      anaesthetized, open-chest pigs (n = 8 for each of the drugs, in addition to the
      control group, n = 6). Vulnerability to fibrillation was evaluated by measuring
      electrical fibrillation threshold (EFT) by means of stepwise increased intensity
      of wide (100 ms) diastolic impulses applied to the ischaemic tissue at a 180
      beats min-1 rate. Monophasic action potential (MAP) duration and conduction time
      in the ischaemic region were also measured. 3. EFT determinations were performed
      before and during periods of ischaemia induced by complete occlusion of the left
      anterior descending coronary artery near its origin. Ischaemic periods of
      increasing duration (30, 60, 90, 120, 150 s) were induced to determine the
      electrophysiological changes, of EFT especially, leading to fibrillation. 4. In
      the absence of ischaemia, all three drugs, administered by intravenous route (1
      mg kg-1 plus 0.04 mg kg-1 min-1) increased EFT to a similar extent (from
      approximately 7 to 10 mA), despite a 25% prolongation of conduction time. 5.
      During ischaemia, none of the drugs prevented the fall in EFT towards 0 mA,
      resulting in spontaneous fibrillation. After 30 s of ischaemia, they no longer
      had any capacity for raising EFT and, after 60, 90 and 120 s of ischaemia, the
      decrease in EFT was exacerbated. This accelerated reduction in EFT shortened the
      time to onset of fibrillation (after 120 s of ischaemia, 62.5% of fibrillations
      with flecainide instead of 12.5 under control conditions, 75% instead of 25 with
      lignocaine and 50% instead of 25 with disopyramide). The reduction in MAP
      duration due to ischaemia was also significantly accelerated (at 60 s, 178 +/- 5
      ms instead of 192 +/- 4 with flecainide, 175 +/- 3 ms instead of 194 +/- 5 with
      lignocaine and 180 +/- 5 ms instead of 196 +/- 3 with disopyramide) and the
      slowing of conduction was made worse (prolongation of conduction time by 70%
      instead of 50). 6. In conclusion, the antifibrillatory properties normally
      manifested by these drugs are first suppressed, then inverted by ischaemia,
      depending on oxygen debt varying with severity and duration of ischaemia.

PMID- 9031760
TI  - Prominent sympathetic purinergic vasoconstriction in the rabbit splenic artery:
      potentiation by 2,2'-pyridylisatogen tosylate.
AB  - 1. Vasoconstrictions induced by transmural electrical field stimulation were
      frequency-dependent from 2 to 32 Hz in the rabbit isolated splenic artery. All
      contractions were abolished in the presence of tetrodotoxin 1 microM or
      guanethidine 100 microM. Stimulation at a frequency of more than 32 Hz induced
      both neurogenic and myogenic responses. 2. Prazosin (1 microM) did not
      significantly affect vascular contractions to electrical stimulation.
      Desensitization of P2X-purinoceptors with alpha, beta-methylene ATP (alpha, beta
      meATP, 3 microM) abolished the contractions to stimulation at 2-8 Hz and
      inhibited more than 80% of the vascular response at 16 Hz, but it did not
      significantly change the responses at 32 Hz. Contractile responses at 32 Hz were
      inhibited by a combination of prazosin and alpha, beta-meATP. Effects of
      pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid tetrasodium salt (a
      selective P2X-purinoceptor antagonist) and suramin (a competitive P2-purinoceptor
      antagonist) on the neurogenic responses were investigated in this study. 3. 2,2'
      Pyridylisatogen tosylate (PIT, 0.3-3 microM) significantly potentiated the
      vasoconstrictions to electrical stimulation at 2-32 Hz in a concentration
      dependent manner. Potentiated responses were restored to the control level 30 min
      after washing. Concentration-dependent response curves for noradrenaline (NA) or
      alpha, beta-meATP were not significantly changed by 3 microM PIT, and
      vasoconstriction by adenosine 5'-triphosphate (ATP, 300 microM) was unaffected by
      PIT. Coomassie brilliant blue-G (1 microM), which shares the potentiating effect
      on a recombinant P2Y-purinoceptor with PIT (King et al., 1996), did not inhibit
      or potentiate the purinergically-mediated component of the response to
      sympathetic nerve stimulation. The selective alpha 2-adrenoceptor antagonist
      yohimbine (1 microM) also potentiated the vascular responses to electrical
      stimulation. 4. The present results indicate that ATP evokes postjunctional
      contractile responses at low and high frequency electrical stimulation of
      sympathetic nerves supplying the rabbit splenic artery. PIT potentiates the
      responses to sympathetic (purinergic) nerve stimulation; this appears to be
      mainly via prejunctional rather than postjunctional actions.

PMID- 9031761
TI  - Anti-insulin-like growth factor-I activity of a novel polysulphonated distamycin
      A derivative in human lung cancer cell lines.
AB  - 1. The purpose of this study was to investigate the antiproliferative effect and
      the modulation of the mitogenic insulin-like growth factor-I (IGF-I) system by
      FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative
      compounds, on two human non-small cell lung cancer (N-SCLC) cell lines. 2. For
      cell growth studies the colorimetric MTT and the thymidine incorporation assays
      were performed; the presence of IGF-I and IGF-binding proteins in conditioned
      media was revealed by radioimmunoassay and Western ligand blot, respectively.
      Variations at the IGF-I-receptor level were tested by binding studies on cell
      monolayers. 3. A significant concentration- and time-dependent cytostatic
      activity of FCE 26644 (IC50 approximately 200 micrograms ml-1 at 72 h) compared
      to its analogue FCE 27784 (IC50 > 800 micrograms ml-1) was observed in both cell
      lines studied. The IGF-I-stimulated proliferation of the IGF-I-responsive A549
      cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was
      inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF-I-like material
      and reduced the IGF-I binding (IC50 > 100 micrograms ml-1) in both A549 and Ca-Lu
      1 cell lines. FCE 26644 (100 micrograms ml-1) did not affect the KD
      (approximately 0.5 nM) but reduced the Bmax and the number of receptor sites
      (50%). 4. Our findings demonstrate that the ability to down-regulate the cell
      proliferation of N-SCLC cell lines, shown by FCE 26644, depends at least
      partially, on interference with the "IGF-I mitogenic system'.

PMID- 9031762
TI  - Localization of a parathyroid adenoma by the addition of pinhole imaging to Tc
      99m sestamibi dual-phase scintigraphy. Report of a case and review of experience.
AB  - Scintigraphy using Tc-99m has been shown to be highly sensitive in localizing
      abnormal parathyroid glands in patients with hyperparathyroidism. False-negative
      studies most often are attributed to glandular size or location. The authors
      report a case of negative parathyroid imaging using standard dual-phase
      technique, which was converted to a positive study by the addition of a pinhole
      view. During a 1-year period, the authors systematically added an anterior
      pinhole image of the neck to all equivocal or negative Tc-99m studies. Five of 19
      patient studies were pinhole-image positive and standard-image negative or
      equivocal. In selected patients undergoing Tc-99m scintigraphy for
      hyperparathyroidism, the addition of a pinhole view may enhance study sensitivity
      and the confidence in interpretation.

PMID- 9031763
TI  - Clinical application of Tc-99m tetrofosmin scintigraphy in patients with cold
      thyroid nodules. Comparison with color Doppler sonography.
AB  - We prospectively studied 26 patients with cold thyroid nodules (five malignant
      and 21 benign nodules) on Tc-99m pertechnetate scintigraphy to investigate the
      diagnostic value of Tc-99m tetrofosmin scintigraphy and color-Doppler sonography
      in differentiating malignant from benign thyroid nodules. In each patient, Tc-99m
      Tetrofosmin uptake in the nodule and intranodule vascularity were assessed
      semiquantatively. Both the uptake and vascularity were classified as low, Iso or
      high. Eight out of 26 nodules showed high Tc-99m tetrofosmin uptake; five of them
      were malignant. Eight (including four malignant tumors) out of 26 nodules showed
      increased vascularity compared with normal thyroid tissue on color-Doppler
      sonography. In six out of eight patients with high uptake of Tc99m-tetrofosmin,
      increased vascularity was observed. The sensitivity, specificity, negative
      predictive value, and positive predictive value of Tc-99m tetrofosmin
      scintigraphy and color-Doppler sonography were determined to be 100% and 80%, 85%
      and 80%, 62% and 50%, and 100% and 94%, respectively. We conclude that color
      Doppler sonography seems to have limited value in the detection of malignant
      thyroid nodules. However, Tc-99m tetrofosmin scintigraphy is a sensitive method
      to use in diagnosing malignant nodules, although it is not specific for the
      detection of malignant nodules.

PMID- 9031764
TI  - Bone marrow imaging of bone marrow transplanted multiple myeloma patients.
AB  - Eighteen bone marrow transplanted multiple myeloma patients had imaging studies
      on 24 occasions with radiography as well as bone and bone marrow scintigraphy
      within 2 months. Twelve of the radionuclide bone marrow studies were performed
      with Tc-99m human serum albumin colloid and 12 were performed with a Tc-99m
      tagged monoclonal antigranulocyte antibody. The total detection rate of bone
      marrow lesions increased by 5% when the findings on bone marrow scintigraphy were
      combined with the findings and at radiography bone scintigraphy. For lesions in
      the spine and sacrum, the increase was 25% and 33% respectively, including
      patients with focal radiotherapy. Peripheral red bone marrow expansion was noted
      in 17 patients. In a comparison of Mab and Tc-99m HSA colloid imaging, Mab
      resulted in a higher bone marrow to soft tissue uptake and to a much smaller part
      of the skeleton being obscured by liver and spleen uptake. It is concluded that
      bone marrow imaging is valuable for showing red bone marrow distribution. It
      thereby shows possible sites for malignant lesions; it also shows that Mab
      imaging is superior to Tc-99m HSA colloid imaging in bone marrow transplanted
      multiple myeloma patients.

PMID- 9031765
TI  - Gastric duplication cyst. Scintigraphy and correlative imaging.
AB  - Gastric duplication cysts are uncommon congenital anomalies, and examples imaged
      with scintigraphy are rarely reported in the literature. The authors report an
      infant with duplication of the stomach, which was extensively evaluated using
      scintigraphy, ultrasound, computed tomography, and upper gastrointestinal series.
      The role of multimodality imaging is discussed, and correlative surgical and
      histologic findings are presented.

PMID- 9031766
TI  - Asystole during dipyridamole infusion in patients without coronary artery disease
      or beta-blocker therapy.
AB  - The authors report two patients without coronary artery disease who experienced
      asystole during the IV infusion of dipyridamole on routine TI-201 myocardial
      perfusion imaging and review the literature for possible explanations of this
      rare side effect. Until now, this side effect was only reported in patients with
      coronary artery disease or beta-blocker therapy. Yet, the cases lacked both
      concomitant factors and autonomic dysregulation is suggested as a cause for
      asystole.

PMID- 9031767
TI  - Aseptic necrosis. A scintigraphic imitator of osseous involvement in Ga-67 avid
      lymphoma.
AB  - Based on the data by Armas et al, avascular necrosis, a not uncommon treatment
      associated complication in patients with lymphoma, it should be easily
      distinguishable from osseous lymphomatous involvement in patients with Ga-67 avid
      lymphoma. In avascular necrosis, Ga-67 uptake will be either absent, decreased,
      or normal, whereas in lymphoma Ga-67 uptake will be increased. The authors
      present a patient with Hodgkin's disease who had new foci of simultaneously
      increased Ga-67 and Tc-99m MDP uptake because of avascular necrosis as proven by
      biopsy and long-term follow-up. The authors hypothesize that a possible
      explanation for the discrepancy between this patient report and the series by
      Armas et al may be that increased Ga-67 is a delayed phenomenon related to
      healing.

PMID- 9031768
TI  - The 'mouse face' appearance of the vertebrae in Paget's disease.
AB  - Paget's disease is occasionally found as an incidental finding on bone scans
      performed for the evaluation of metastatic disease, which causes a diagnostic and
      a subsequent therapeutic dilemma. We have previously described the "Mouse Face"
      appearance of vertebrae on bone scans (increased uptake in the vertebral body,
      posterior elements, and the spinous process), which was fairly specific for
      Paget's disease in a small series. This retrospective study was undertaken to
      determine if this observation holds true in a larger series. Bone scans performed
      in 2,881 patients were randomly selected, and were reviewed by 2 physicians.
      Thirty-nine cases with a "Mouse Face" appearance were identified. Diagnosis was
      established in 30 of the 39 patients by correlative radiographic studies and/or
      clinical follow-up. Twenty patients were referred for the evaluation of possible
      metastases, and 7 were found to have metastases at the sites of "Mouse Face". The
      other 13 had Paget's disease. However, 6 of the 7 patients with metastases had
      extravertebral findings compatible with multiple metastases, and the remaining
      patient had a "Mouse Face" lesion only, with a question of metastases. Ten
      patients were evaluated for Paget's disease or others, and none of them had
      metastases at the site of the "Mouse Face". The "Mouse Face" appearance is more
      suggestive of Paget's disease than metastases even in patients with cancer. These
      patients should be assumed unlikely to have vertebral metastases, unless proven
      by another correlative radiologic study.

PMID- 9031769
TI  - Pertechnetate thyroid uptake is not always suppressed in patients with subacute
      thyroiditis.
AB  - The authors studied the clinical courses and immunologic aspects in 15 patients
      (age range, 32-69 years old; 14 women) with clinical features that were similar
      to subacute thyroiditis (SAT). In 2 patients (group A) whose thyrotropin-binding
      inhibitory immunoglobulins (TBII) and thyroid stimulating antibody (TSAb) showed
      strongly positive activity at the initial visit, Tc-99m pertechnetate thyroid
      uptake (Tc-99m uptake) was elevated (5.6% and 3.8%, respectively, normal; 0.7
      3.0%). In 6 (group B) of 13 other patients, Tc-99m uptake was not completely
      suppressed (2 normal, 4 near normal) and imaging showed uptake in one lobe. In 7
      (group C), however, there was no evidence of uptake in either lobe. Inflammatory
      process was localized in one lobe in all group B patients, and was in both lobes
      in all group C patients but one. Serum TSH levels were detectable in at least 4
      patients (2 group B, 2 group C) low in all. There were no patients in both groups
      B and C in whom TBII and/or TSAb were detected at the initial visit. In SAT,
      marked suppression of Tc-99m uptake may be ascribed mainly to inflammatory
      follicular cell damage, but it is not always suppressed, owing to an association
      similar to Graves' disease and other unknown mechanism(s).

PMID- 9031770
TI  - Ventilation-perfusion scintigraphic correlation with multimodality imaging in a
      proven case of Swyer-James (Macleod's) syndrome.
AB  - The scintigraphic findings in a rare case of a unilateral matched ventilation
      perfusion defect, Swyer-James (Macleod's) syndrome, are presented. A 40-year-old
      man underwent ventilation/perfusion imaging for acute onset of dyspnea. The scan
      showed markedly diminished ventilation, vascular flow, and perfusion unilaterally
      on the left hemithorax. Chest radiography showed hyperlucency of the left lung.
      Pulmonary angiography showed left-sided hypovascularity, and the CT scan of the
      chest showed apical bullae and peribronchial thickening of the left lung.
      Ventilation/perfusion imaging and other radiologic assessment, along with the
      patient's medical history, confirmed the diagnosis of the Swyer-James syndrome.
      This condition should be considered as a differential diagnosis in a patient with
      unilaterally matched ventilation/perfusion deficits without an obvious etiology.

PMID- 9031772
TI  - Four ectopic parathyroid glands detected with Tc-99m sestamibi.

PMID- 9031771
TI  - Bilateral periventricular nodular heterotopia. PET and MRI of a patient with
      focal seizures.

PMID- 9031773
TI  - Rapid transit of tracer to the kidneys and urinary bladder in radionuclide
      cisternography. A sign of CSF leak.

PMID- 9031774
TI  - False-positive I-131 whole-body imaging after I-131 therapy for a follicular
      carcinoma.

PMID- 9031775
TI  - TI-201 uptake in reactive lymphadenopathy.

PMID- 9031776
TI  - Site of mistletoe injection observed on In-111 OncoScint imaging.

PMID- 9031777
TI  - Massive cardiac Ga-67 uptake in a child with pulmonary hypertension, heart
      failure, and bleeding.

PMID- 9031778
TI  - Decrease of the central type benzodiazepine receptor in cortical tubers in a
      patient with tuberous sclerosis.

PMID- 9031779
TI  - Tc-99m DTPA delayed SPECT imaging of neurofibromatosis.

PMID- 9031781
TI  - Current readings in nuclear medicine.

PMID- 9031780
TI  - Artifact on bone SPECT of the lumbar spine.

PMID- 9031782
TI  - Viral lesions of the mouth in HIV-infected patients.
AB  - Viral lesions of the mouth in patients with HIV infection are common and these
      diseases any be a marker for HIV and disease progression. We review the spectrum
      of oral viral manifestations and discuss treatment modalities. The most common
      Epstein-Barr virus (EBV)-induced disorder in HIV-infected patients is oral hairy
      leukoplakia. EBV-related oral B-cell and T-cell lymphoma in AIDS patients has
      been described repeatedly. Herpes virus type 1 and rarely type 2 may lead to
      painful and resistant oral ulcers, and systemic treatment with acyclovir,
      valaciclovir or famciclovir is indicated. In acyclovir-resistant cases foscarnet
      is the treatment of choice. In recent years it has been documented that Kaposi's
      sarcoma, which often affects oral mucosa, is probably induced by herpesvirus type
      8. Cytomegalovirus was found in 53% of cases with herpesviridae-induced mucosal
      ulcers as the only ulcerogenic viral agent in AIDS patients. In severe
      cytomegalovirus infection treatment with ganciclovir is helpful. Viral warts
      induced by different HPV may occur in the mouth. Several physical treatment
      modalities are possible in the oral mucosa. In AIDS patients mollusca contagiosa
      may occur as large and atypical lesions in the face and lips and rarely in the
      oral cavity. Cryotherapy is a bloodless treatment in such patients.

PMID- 9031784
TI  - Quantitating hair loss in women: a critical approach.
AB  - BACKGROUND: Assessing how many hairs are actually shed by patients complaining of
      hair loss is a difficult task. Many methods have been proposed, but all need
      standardization. METHODS: We examined 234 women complaining of hair loss.
      Alopecia areata and scarring alopecias were excluded. Eighty-nine of the patients
      had an apparently normal density of hair. Seventy-four were classified as Ludwig
      stage I, 37 as Ludwig II and 15 as Ludwig III. In 19 patients, classification had
      not been recorded. They were tested with the pull test (PT), daily count (DC) and
      wash test (WT). Telogen percentage was obtained by a trichogram in 43 patients.
      RESULTS: Dispersion of the data was very high. The medians of the PT, DC and WT
      were 0.6, 60.5 and 122 hairs, respectively. The telogen median of percentage was
      16. In patients with normally dense hair, the PT, DC and WT means were
      significantly higher than in those with Ludwig stages I-III. Telogen means did
      not differ. WT values correlated significantly with those of the DC and PT, and
      DC values did so with those of the PT. By contrast, telogen percentage did not
      correlate with WT, DC and PT values. WT values and telogen percentage increased
      in autumn, the latter preceding the WT by 1 month. CONCLUSIONS: The methods
      adopted and the problem of 'normality' are critically analyzed. Subjects
      complaining of hair loss proved to shed a higher number of hairs than those with
      various degrees of baldness. The PT is a poorly sensitive method, while telogen
      percentage is not correlated with the severity of hair loss. As the DC is a
      cumbersome procedure, the WT is probably the best method to adopt.
      Standardization of methods and assessment of normality in prepubertal children
      are imperative.

PMID- 9031783
TI  - Tinea capitis in adults: misdiagnosis or reappearance?
AB  - BACKGROUND: According to the literature, tinea capitis in adults is supposed to
      be rare; we have recently observed a significant increase in cases. METHODS:
      Epidemiological, clinical and mycological features were studied in all adult
      tinea capitis diagnosed over 1 year in our department. RESULTS: Eight cases were
      observed: 75% of them were women, 50% never traveled and 62.5% had an underlying
      immunosuppressive disease. Scalp scaling and alopecia were the most frequent
      clinical features. A zoophilic dermatophyte was recovered in 50% of cases.
      CONCLUSION: These cases represent 11% of all tinea capitis observed in the same
      period of time (higher than the 3-5% observed in the literature). Secretion of
      sebum and colonization by Pityrosporon orbiculare are supported to protect the
      scalp against dermatophytic invasion after puberty, but an immune defect may also
      facilitate hair invasion. The erroneous notion of the disease being uncommon and
      the frequent atypical clinical presentation require a high degree of clinical
      suspicion.

PMID- 9031785
TI  - Excess benign melanocytic naevi in renal transplant recipients.
AB  - BACKGROUND: Some studies indicate that malignant melanoma occurs more frequently
      in renal transplant recipients than in the normal population. The development of
      excess benign melanocytic naevi is regarded as an indicator of the risk for
      malignant melanoma. OBJECTIVE: This study was undertaken to evaluate the
      prevalence of benign melanocytic naevi in adult renal transplant patients.
      METHOD: All benign melanocytic naevi irrespective of size were counted in 76
      patients with renal transplants and were compared to naevus counts in 55 sex- and
      age-matched healthy controls. RESULTS: The mean total number of benign
      melanocytic naevi was significantly higher (p < 0.001) in renal transplant
      patients than in the control group: 93.6 +/- 52.2 and 36.1 +/- 29.9,
      respectively. The most evident increase occurred on the palms/soles and
      back/buttocks. A positive, although not significant, correlation between naevus
      counts and duration of immunosuppression was found. CONCLUSION: Renal transplant
      recipients have an increased number of benign melanocytic naevi and should be
      considered as a risk group for malignant melanoma.

PMID- 9031786
TI  - Clinical review of 247 case records of Spitz nevus (epithelioid cell and/or
      spindle cell nevus).
AB  - BACKGROUND: Spitz nevus has clinically been described as a dome-shaped usually
      nonpigmented papular or nodular lesion variable in color from pink to red.
      OBJECTIVES: To give an exhaustive description of the clinical features of the
      Spitz nevus from a large series of 247 patients. METHODS: A retrospective
      analysis of the clinical features of 247 Spitz nevi excised from 1974 to 1993 has
      been performed. We evaluated the following features: age, sex, anatomical
      location, clinical and histopathologic features; descriptive statistics were
      calculated and relationships among the above variables were assessed. RESULTS:
      Most lesions were pigmented (71.7%), located on the lower extremities (43.3%),
      more frequent in the first decade (55.8%) and in females (57.9%). The
      nonpigmented type was more frequent in the head or neck region, whereas the
      pigmented types were more frequent on the lower extremities. Besides, these types
      showed different histopathologic features: the spindle cells usually predominated
      in the flat pigmented type, whereas dome-shaped types were usually composed of
      both spindle and epithelioid cells. CONCLUSIONS: In our patients, the pigmented
      Spitz nevi were more common than the nonpigmented ones; furthermore pigmented and
      nonpigmented Spitz nevi showed different anatomical locations and different
      histopathologic features.

PMID- 9031787
TI  - Symmetric lipomatoses in female patients.
AB  - BACKGROUND: Symmetric lipomatoses are characterized by marked symmetric
      deposition of diffusely distributed fatty tissue. Though relatively common
      disorders, they are rather rarely reported in the literature, possibly being
      misdiagnosed as general obesity. While the differential diagnosis of symmetric
      lipomatosis versus general obesity may not appear difficult in males, it is
      obviously problematic in females. OBSERVATIONS: We describe the findings in 6
      representative female patients with symmetric lipomatoses: 3 with benign
      (multiple) symmetric lipomatosis and 3 with female zonal obesity. The former
      disorder was characterized by massive, firm, symmetric fat deposition
      predominantly around the neck and shoulder girdle and was clearly associated with
      alcohol abuse and/or liver disease. There were no malignant tumors of the upper
      airways. In the latter case, fatty tissue had accumulated mainly at the buttocks
      and thighs but characteristically spared the feet and hands. Tenderness was a
      common symptom. This disorder showed familial predisposition. Histology in both
      cases revealed normal fatty tissue which was neither encapsulated nor septally
      divided. CONCLUSIONS: We suggest that the term 'symmetric lipomatoses' refers to
      two separate disorders, benign (multiple) symmetric lipomatosis and female zonal
      obesity.

PMID- 9031788
TI  - Pityriasis rotunda: a survey of 42 cases observed in Sardinia, Italy.
AB  - BACKGROUND: Pityriasis rotunda (PR) is an uncommon dermatosis characterized by
      multiple, round or oval, sharply demarcated scaling patches that are dyschromic
      and asymptomatic. It has been described in Japanese and in blacks, usually in
      association with certain infective or malignant systemic diseases. OBJECTIVE: The
      aim of this study is to further clarify this rare entity which in Italy seems to
      be confined to the island of Sardinia. METHODS: We studied 42 Sardinian patients,
      22 males and 20 females, in an age range of 3-32 years. In 29 cases, the disease
      involved more than one family member. The patients were observed in Cagliari, the
      capital city of Sardinia. RESULTS: Bacterial, viral and fungal investigation
      yielded negative results. Haematochemical and immunological examination and
      thyroid, hypophyseal and adrenal hormones did not reveal any alterations. No
      systemic pathologies were found associated with the disease. CONCLUSIONS: The
      cases studied by us and those previously reported seem to indicate the presence
      of two distinct types of PR with significant prognostic differences.

PMID- 9031789
TI  - Nailfold capillary microscopy in patients with anticardiolipin antibodies: a case
      control study.
AB  - BACKGROUND AND DESIGN: This case-control study was undertaken to determine
      whether anticardiolipin antibodies (ACA) are responsible for particular
      abnormalities in nailfold capillary microscopy (NCM). Cases comprised 33
      consecutive patients positive for ACA (24 women and 7 men). Controls comprised
      the same number of ACA-negative patients, with the same sex ratio, the same
      diagnosis and the most similar duration of disease possible. Clinical data, serum
      samples and NCM recordings were obtained from all patients and controls. RESULTS:
      In each group, 22 patients had connective-tissue-related disorders and 11 various
      other diseases. In ACA-positive patients, the mean IgG ACA titre was 39 +/- 58
      IgG phospholipid units. Cases and controls displayed various cutaneous
      manifestations. In ACA-positive patients, there were Raynaud's phenomenon (54%),
      cutaneous vasculitis (24%), scleroderma changes (18%), photosensitivity (9%), a
      history of digital gangrene (6%), malar rash (6%), acrocyanosis (6%), chilblains
      (3%), livedo reticularis (3%) and purpura (3%). Cases and controls exhibited
      numerous NCM abnormalities. In ACA-positive patients, they included haemorrhages
      (54%), oedema (24%), bushy capillaries (21%), disordered capillaries (18%),
      capillary bed disorganization (12%), capillary rarefaction (9%), giant
      capillaries (6%) and 'desert areas' (3%). There were no correlations between the
      ACA titres on the one hand and the number of cutaneous manifestations or NCM
      abnormalities on the other. CONCLUSIONS: ACA-positive patients frequently exhibit
      clinical skin lesions and abnormal NCM. In this study, these lesions and NCM
      abnormalities resembled those of the matched ACA-negative controls.

PMID- 9031790
TI  - Erythema induction by ultraviolet radiation points to a possible acquired defense
      mechanism in chronically sun-exposed human skin.
AB  - BACKGROUND: It is generally accepted that a UVA-induced erythema is difficult to
      detect except in the most sensitive individuals. OBJECTIVE AND METHODS: As UVA
      effects on human skin and skin cells have been shown to depend strongly on
      anatomical body sites, UVA I, UVA I + II and solar simulator radiations were
      compared in their ability to induce erythema and melanin pigmentation responses
      in individuals with skin types I-IV on both previously sun-exposed (arms,
      forearms, thighs) and nonexposed body sites (buttocks). RESULTS: Erythema
      induction by UVA I on previously nonexposed skin sites followed a dose response
      in all skin types which was contrary to the absence of erythema induction seen on
      previously sun-exposed sites. Melanin expression followed a dose and skin type
      response and was shown to be more enhanced in previously exposed skin and in skin
      types III and IV. In contrast, UVA I + II induced erythema on nonexposed skin
      areas and to a lesser extent on frequently sun-exposed skin. Melanin production
      by UVA I + II was similar to that seen with UVA I alone in individuals of skin
      types II and III. Solar simulator radiation was very efficient in erythema
      induction regardless of previous sun exposure of skin. CONCLUSIONS: We have found
      that contrary to the widespread opinion that UVA and in particular UVA I could
      not induce a significant erythema, this waveband is capable of measurable
      erythema induction on skin nonexposed to sunlight. The diminished erythema
      induction by UVA I on chronically sun-exposed skin suggests the possibility of a
      defense mechanism against UVA-induced damage in this tissue.

PMID- 9031791
TI  - 'Patient's delay'--analysis of the preclinical phase of occupational dermatoses.
AB  - BACKGROUND: In order to cure diseases effectively it is important that they are
      detected in their early stages so that medical precautions can be taken. With job
      related disorders it is conceivable that anxiety concerning the workplace, as
      well as other factors of a demanding nature, may lead to a further delay of
      diagnosis and treatment. OBJECTIVE: The study was carried out for the purpose of
      gathering information about the patients' reactions in the preclinical phase of
      job-related eczema. METHODS: 79 patients suffering from a job-related skin
      disease were questioned. The patients were divided up into groups according to
      their respective delay and the results evaluated in line with the method of
      logistic regression. RESULTS: The average delay was 8.6 months. Fear of losing
      their job was mentioned by most participants as the reason for the postponement
      of seeking medical care. People with a long delay were mainly men, senior and
      Swiss citizens, those with a higher education and those with a longer
      professional training. CONCLUSION: Patient delay in occupational dermatology
      highly depends on the support of employers and on the counseling of workers on
      job-related skin disease and their insurance protection.

PMID- 9031792
TI  - Development of malignant melanoma after repeated topical photodynamic therapy
      with 5-aminolevulinic acid at the exposed site.
AB  - We report the case of a 82-year-old man who, after multiple treatments with
      aminolevulinic acid photodynamic therapy for solar keratoses and superficial
      squamous cell carcinomas, developed malignant melanoma at the exposed site on the
      scalp.

PMID- 9031793
TI  - Necrobiosis lipoidica and silicotic granulomas on Muller's phlebectomy scars.
AB  - We report an unusual case of concomitant necrobiosis lipoidica and silicotic
      granulomas in scars of phlebectomies on the legs, suggestive of a Koebner
      phenomenon.

PMID- 9031795
TI  - Lichen amyloidosis presenting as a papular pruritus syndrome in a human
      immunodeficiency-virus-infected man.
AB  - A human-immunodeficiency-virus (HIV)-positive man presented with pruritic
      erythematous and flesh-colored papules on his arms and trunk of 1 year's
      duration. The lesions had previously been treated with oral ketoconazole and
      topical emollients with no improvement. Microscopic evaluation of lesional skin
      from his left forearm showed lichen amyloidosis. The patient was started on
      ultraviolet B phototherapy which he received for 2 weeks without improvement.
      Lichen amyloidosis should be added to the differential diagnosis of papular
      pruritus syndrome in HIV-positive individuals.

PMID- 9031796
TI  - Atrophic pigmented dermatofibrosarcoma presenting as infraorbital
      hyperpigmentation.
AB  - BACKGROUND: Pigmented dermatofibrosarcoma is a rare tumor of the skin and
      constitutes 1-5% of all dermatofibrosarcoma. Most cases present as polypoid
      multinodular growth. Occasional cases may be atrophic. We report an extraordinary
      case with progressive infraorbital atrophy. OBSERVATION: A 24-year-old woman came
      to us for a diffuse bluish atrophic lesion over the left infraorbital area. The
      lesion progressed gradually over 2 years. Histologic examination revealed mature
      spindle cell proliferation in the lower dermis and hypodermis. Interspersed were
      some heavily pigmented melanocytes. CONCLUSION: We report an unusual case of
      progressive bluish discoloration and atrophy of the infraorbital area. This is a
      rare manifestation of dermatofibrosarcoma.

PMID- 9031794
TI  - Confluent and reticulated papillomatosis responsive to minocycline.
AB  - Confluent and reticulated papillomatosis (Gougerot and Carteaud) is a distinctive
      clinico-pathologic entity of unknown etiology, whose relationship to fungi is
      still controversial. We report a 15-year-old Japanese male in whom Malassezia
      yeasts were found on direct microscopic examination. Treatment with oral
      itraconazole initially resulted in partial improvement but later became
      ineffective. The rash virtually disappeared with administration of minocycline.
      These observations indicate that the role of Malassezia yeasts in the
      pathogenesis of this disease is probably less important than that of
      microorganisms sensitive to minocycline.

PMID- 9031797
TI  - A case of dermatomyositis complicated by thrombotic thrombocytopenic purpura.
AB  - A 60-year-old man with dermatomyositis was admitted to our hospital because of
      dyspnea and hypertension. He had high fever and convulsive seizures after
      admission. Laboratory examinations showed hemolytic anemia, thrombocytopenia, and
      renal failure. A clinical diagnosis of thrombotic thrombocytopenic purpura (TTP)
      was made. He failed to respond to plasma exchange therapy, pulse therapy with
      methylprednisolone, high-dose gamma-globulin therapy, and antiplatelet therapies
      with ticlopidine, dipyridamole and a prostacyclin analog of beraprost sodium. He
      died on his 17th day in hospital. Autopsy examination revealed widespread
      microthrombi in his kidneys, lungs, spleen, and intestine. Only seven cases of
      dermatomyositis or polymyositis complicated by TTP have been cited in the
      literature. TTP was fatal in 6 of these 7 cases. Early diagnosis and prompt
      treatment may improve the outcome of TTP patients with dermatomyositis.
      Dermatologists should keep in mind that TTP occasionally arises as a serious
      complication of dermatomyositis.

PMID- 9031798
TI  - Acne keloidalis nuchae and tufted hair folliculitis.
AB  - Acne keloidalis nuchae is a chronic, scarring folliculitis that affects mostly
      black patients and is located on the back of the neck of young adults. The course
      is progressive and leads to hypertrophic scarring, chronic abscesses and hair
      loss. We discuss the relationship between acne keloidalis and tufted hair
      folliculitis, pointing out the possibility that tufted hair folliculitis is not a
      specific disease but secondary to other progressive folliculitis like
      folliculitis decalvans, dissecting cellulitis or acne keloidalis.

PMID- 9031799
TI  - Diagnosis of trichothiodystrophy in 2 siblings.
AB  - Trichothiodystrophy (TTD) is a rare autosomal recessively inherited disorder
      which is characterized by sparse and brittle hair with low cystine content. It is
      often associated with physical and mental retardation. We report 2 cases of TTD
      in 2 sibs who were born to related parents. The children showed clinical features
      typical of TTD and in addition other symptoms such as epilepsy, ataxia,
      spasticity, strabismus, atopic dermatitis, dysarthria and hyperextensible
      fingerjoints. The sulfur content of hair was reduced to about 50% of normal
      values and scanning electron microscopy of hair showed trichorrhexis nodosa,
      trichoschisis, missing cuticle scales with weathering of hair shafts. Under
      polarizing microscopy an alternating dark and bright banding was found. The
      present cases show that the correct diagnosis of TTD in practice can be impeded
      for many years because of the heterogeneous clinical appearance and that the
      determination of the sulfur content in hair is a simple but indispensable method.

PMID- 9031800
TI  - Phacomatosis pigmentokeratotica: a patient with the rare melanocytic-epidermal
      twin nevus syndrome.
AB  - We describe a 10-year-old girl affected with a speckled lentiginous nevus and an
      epidermal nevus of the organoid type on corresponding parts of the body. On
      histopathological examination, the lesions showed epidermal hyperpigmentation and
      melanocytic hyperplasia on the one hand and verrucous epidermal acanthosis with
      sebaceous hyperplasia on the other hand. Except for a minor deviation of the
      spine, the patient had no obvious extracutaneous symptoms. Happle et al. have
      recently interpreted the rare co-occurrence of these two types of nevi in spatial
      proximity as an example of twin spotting in human skin and proposed the name
      'phacomatosis pigmentokeratotica'. In most cases, additional skeletal or
      neurological anomalies are found. These are dissimilar from the extracutaneous
      symptoms of the sebaceous nevus syndrome, from which phacomatosis
      pigmentokeratotica should be distinguished. Molecular studies are needed to prove
      the concept of twin spotting and to reveal a link to the extracutaneous
      manifestations.

PMID- 9031802
TI  - Remission of localized cutaneous leishmaniasis in a HIV-positive patient using
      systemic terbinafine.

PMID- 9031803
TI  - Schonlein-Henoch purpura associated with gastric Helicobacter pylori infection.

PMID- 9031801
TI  - Erosive pustular dermatosis of the scalp in skin grafts: report of three cases.
AB  - Three patients developed erosive pustular dermatosis of the scalp (EPDS). Two of
      them, both males, had previously undergone surgical excision for squamous cell
      carcinoma and basal cell carcinoma, and a female experienced avulsive trauma of
      the scalp. The erosive lesions and crusts were located at the site of a skin
      graft; microbiological cultures were negative for bacterial and fungal growth.
      Histological examination ruled out pustular bullous disorders. Topical therapy
      with corticosteroids and antibiotics resulted in clinical remission in only 2
      cases. The third case showed a tendency to recur despite numerous therapeutic
      attempts with oral dapsone and isotretinoin. We conclude that surgical trauma is
      a possible cause of EPDS. Our patients seem to be the first reported cases of
      EPDS in skin grafts following plastic surgical procedures.

PMID- 9031804
TI  - Significance of mitotic cells or clumping cells in p53 immunopositivity of
      Bowen's disease.

PMID- 9031805
TI  - Failure of combination therapy with acitretin and cyclosporin A in 3 patients
      with erythrodermic psoriasis.

PMID- 9031806
TI  - Demonstration of herpes virus 8 in a lymphangioma-like Kaposi's sarcoma occurring
      in a non-immunosuppressed patient.

PMID- 9031807
TI  - Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin
      dependent diabetes: studies using electron microscopy and X-ray diffraction
      techniques.
AB  - Extracellular matrix plays an important role in many physiological functions and
      its abnormalities are thought to play a key role in the pathogenesis of diabetic
      complications. In this paper we used the techniques of electron microscopy,
      immunostaining and X-ray diffraction to document some of the early events in the
      changes of extracellular matrix in a model of insulin dependent diabetes in
      baboons. Our results show that thickening of basement membrane and enlargement of
      mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons
      within 2 years from the onset of diabetes. Concomitant with this was the
      accumulation of type IV collagen and laminin in the mesangium. By contrast, even
      the very sensitive technique of X-ray diffraction failed to demonstrate changes
      in the equatorial direction of collagen molecules of the skin and tendon. We
      conclude that changes of glomerular extracellular matrix are demonstrable early
      in insulin dependent diabetes even in prepubertal baboons. These can be used as
      endpoints in evaluating the efficacy of pharmacological agents such as
      aminoguanidine in preventing diabetic complications.

PMID- 9031809
TI  - Incidence of IDDM in children in urban population in southern India. Madras IDDM
      Registry Group Madras, South India.
AB  - This study was carried out to estimate the incidence of childhood insulin
      dependent diabetes mellitus (IDDM) in an urban southern Indian, population. A
      registry for IDDM has been set up in the city of Madras. South India. Details of
      newly diagnosed IDDM children, aged less than 15 years, were analysed
      retrospectively, for a period of 1991-1994. Primary sources were government and
      service hospitals, large diabetes clinics and secondary sources were diabetes
      camp, private diabetologists and endocrinologists. A capture-recapture method was
      used and the estimate of case in the population (1991 census) was calculated.
      Incidence (case/100,000) was calculated in the total group and then for boys and
      girls separately. The incidence for the 4 year period was 10.5/100,000/year (CI
      5.0). The corresponding values for boys and girls were 12.6 +/- 11 and 9.6 +/-
      4.7 respectively. The peak incidence was between 10 and 12 years. This is the
      first population based incidence data from India and showed that the incidence of
      childhood IDDM is not low in urban children.

PMID- 9031808
TI  - Islet-cell antibodies in malnutrition-related diabetes mellitus from north India.
AB  - The etiology of malnutrition-related diabetes mellitus (MRDM)--protein-deficient
      pancreatic diabetes (PDPD) and fibro-calculous pancreatic diabetes (FCPD)-is
      unclear. We studied the role of autoimmunity against pancreatic islet cells in
      the etiology of these two subtypes of MRDM by measuring islet-cell antibodies
      (ICA) in 23 patients with PDPD, 25 with FCPD and 62 with Type 1 diabetes. Three
      patients (13%) with PDPD had detectable ICA. Including a patient with a high
      titre of ICA (> 80 JDF units). The frequency of ICA in patients with PDPD was
      significantly lower than subjects with Type 1 diabetes (22/62, 35%; P < 0.05).
      Among patients studied at onset. ICA prevalence was lower in the PDPD patients
      (1/7, 14%) compared to subjects with Type 1 diabetes (8/20, 40%). No patient of
      FCPD had detectable ICA (P < 0.001 vs. Type 1 diabetes subjects). We conclude
      that autoimmunity may play a role in the etiology of some patients with the PDPD
      subtype of MRDM. However, FCPD is unlikely to have an autoimmune etiology.

PMID- 9031810
TI  - Predicting long-term glycemic control of post-educational type II diabetic
      patients by evaluating serum 1,5-anhydroglucitol levels.
AB  - 1,5-Anhydroglucitol (1.5-AG) is known to closely reflect diabetic control within
      several days. The possibility of predicting long-term glycemic control after an
      educational hospitalization of type II diabetic patients was investigated by
      examining the relationship between changes in serum 1,5-AG levels after a short
      term trial home stay following an educational program and long-term changes in
      glycosylated hemoglobin A1c (HbA1c) levels after discharge. After 22 patients
      with type II diabetes had successfully completed the educational hospitalization
      program, they returned as outpatients for 5 nights in a row. Changes in serum 1,5
      AG levels were determined during this period. The HbA1c levels were then
      determined over a period of 3 months after discharge, and the relationship
      between changes in 1,5-AG and HbA1c levels was examined. Changes in serum 1,5-AG
      levels during the 5-day trial home stay and the changes in HbA1c levels during
      the 3 months after discharge from the hospital were found to be significantly
      correlated (r = 0.70, P < 0.01). A comparison of the decreased group, which
      exhibited a decrease in 1.5-AG levels of 5.0 mumol/l or more during the trial
      home stay, and the unchanged group, revealed that increases in body mass index 3
      months after discharge were significantly higher in the decreased group (1.2 +/-
      0.4%) than in the unchanged group (0.2 +/- 0.5%) (P < 0.05). Determination of
      serum 1,5-AG levels of patients with type II diabetes before and after a trial
      home stay following educational hospitalization was found to be useful in
      identifying patients at high risk of recurrence of poor glycemic control in the
      future.

PMID- 9031811
TI  - Dopamine-sodium relationship in type 2 diabetic patients.
AB  - Diabetes mellitus is known to be associated with sodium retention. The aim of the
      present paper was to investigate the possible role of the renal dopaminergic
      system in the disturbed sodium homeostasis of Type 2 diabetic patients. The
      urinary dopamine excretion, which represents the local kidney production, was
      lower in Type 2 diabetic patients as compared to controls and decreased in
      insulin treated patients as compared to patients treated without insulin. Urinary
      dopamine excretion correlated positively with sodium excretion in non-insulin
      treated patients and in controls, but not in insulin treated patients. In
      contrast to findings in healthy volunteers, an intravenous sodium load failed to
      increase the dopamine excretion in Type 2 diabetic patients, despite similar
      increments in sodium excretion. A low-dose dopamine infusion caused significantly
      lower natriuretic responses in insulin treated Type 2 diabetic patients as
      compared to controls, but not in non-insulin treated patients. These findings
      suggest that Type 2 diabetic patients display a derangement of the renal
      dopaminergic system, which is accentuated by insulin treatment.

PMID- 9031812
TI  - Emotional adjustment and metabolic control in newly diagnosed diabetic persons.
AB  - Emotional reactions to diagnosis were examined in a random sample of newly
      detected diabetic patients (n = 71) and compared with the indicators of glycemic
      control in a one-year-follow-up period. The social and emotional factors subscale
      of the diabetes care profile was used to determine the subjectively experienced
      burden, negative feelings and positive coping abilities. The initial struggle
      against the disease indicated three characteristic emotional patterns. Feelings
      of being able to cope with the disease predominated in group 1 (n = 36), negative
      emotional reactions, but with the ability to cope were observed in group 2 (n =
      17) and negative feelings combined with weak coping abilities in group 3 (n =
      18). The long-term indicators of glycemic control were shown to be worst in group
      3 and best in group 1. Subjective perception of the disease was not associated
      with sociodemographic variables, with the exception of perceived coping abilities
      which were better in more educated persons and those with more familial support.

PMID- 9031813
TI  - Day-night blood pressure variation in normotensive and hypertensive NIDDM
      patients with asymptomatic autonomic neuropathy.
AB  - In order to assess the characteristics of day-night blood pressure (BP) variation
      in normotensive and hypertensive non-insulin-dependent diabetic (NIDDM) patients
      with asymptomatic autonomic neuropathy, 54 NIDDM patients and 13 healthy control
      subjects were studied by casual BP measurements and 24-h ambulatory blood
      pressure monitoring. Signs but not symptoms of autonomic neuropathy were
      documented by results of standard cardiovascular function tests in each patient.
      Daytime (06:00-22:00) and nighttime (22:00-06:00) BP values were separately
      analyzed and delta day-night BP values and diurnal index were determined.
      Patients were classified as being normotensive or having hypertension according
      to the casual BP values and medical history. In normotensive NIDDM patients (n =
      30), nighttime systolic BP was significantly higher, whereas delta day-night
      systolic and delta day night diastolic BP values as well as diurnal index were
      considerably lower than those in control subjects (n = 13). In hypertensive NIDDM
      patients (n = 24), similar alterations were found at higher BP levels. No
      significant difference was found in BP values if normoalbuminuric and
      microalbuminuric NIDDM patients were compared. 'Non-dipper' phenomenon could be
      found in normotensive and hypertensive NIDDM patients with asymptomatic autonomic
      neuropathy, suggesting that relative sympathetic overdrive due to incipient and
      predominantly parasympathetic impairment of cardiovascular innervation might play
      a role in early alterations of circadian BP variation.

PMID- 9031814
TI  - Epidemiology and determinants of blood glucose self-monitoring in clinical
      practice.
AB  - The aim of this study was to describe the epidemiology of self-monitoring of
      blood glucose and to identify specific characteristics of those subgroups of
      diabetic patients treated with insulin that are most likely to monitor their
      blood glucose according to medical recommendations. Data were collected on 1384
      insulin-treated patients, enrolled from 35 diabetic outpatient clinics and 49
      general practitioners' offices between December 1993 and June 1994. Seventeen
      Italian regions out of 20 were included in the study. Our data show that 418
      (31%) diabetic patients treated with insulin had never practised blood glucose
      self-monitoring. In addition, only 242 patients (18.2%) self-monitored their
      glycemia with a mean frequency of at least once a day (29.7% among insulin
      dependent diabetes mellitus (IDDM) and 13.9%, among insulin-treated non-insulin
      dependent diabetes mellitus (NIDDM-IT) patients). Patients' characteristics
      associated with a higher probability of practising blood glucose self-monitoring
      were age below 50 years, being treated at a diabetic outpatient clinic,
      hypertension, need of three or more insulin injections per day, history of
      hypoglycemic episodes, ability to self-manage insulin doses. Our study calls for
      vigorous efforts aimed at promoting the incorporation of clearly-defined
      educational programs at each level of care, in order to improve the motivation
      and self-care of diabetic patients. Furthermore, studies are necessary to
      identify subgroups of diabetic patients that truly need to self-monitor blood
      glycemia, and to assess the efficacy of the practice of self-monitoring of blood
      glucose in improving metabolic control and reducing acute and long-term diabetic
      complications.

PMID- 9031815
TI  - Frontal P300 decrements, childhood conduct disorder, family history, and the
      prediction of relapse among abstinent cocaine abusers.
AB  - P300 event related brain potentials were studied in 49 cocaine dependent
      patients, abstinent for 1-5 months, and 20 healthy, non-drug-dependent controls.
      Patients were assigned to one of two subgroups based on the presence/absence of a
      DSM-IIIR diagnosis of antisocial personality disorder (ASPD). Analyses of P300s
      recorded during a visual selective attention task revealed reduced amplitudes at
      frontal electrode sites among patients with ASPD, relative to the ASPD negative
      patient and control groups. The frontal P300 decrement was significantly
      correlated with the number of childhood conduct disorder symptoms, but not with
      the presence/absence of a family history of alcoholism. A secondary analysis
      examined the relationship between P300 amplitude among cocaine dependent patients
      and their future behavior, i.e., relapse versus continued abstinence.
      Discriminant function analysis revealed that P300 amplitude alone accurately
      identified 70.6% of the patients who later relapsed, and 53.3% of the patients
      who did not.

PMID- 9031816
TI  - Prevalence and demographic correlates of symptoms of last year dependence on
      alcohol, nicotine, marijuana and cocaine in the U.S. population.
AB  - The prevalence of last year use of alcohol, cigarettes, marijuana and cocaine in
      the U.S. population and conditional prevalence of a proxy measure of last year
      dependence among last year users of each drug class were assessed as a function
      of age, gender and ethnicity. Analyses were based on three aggregated waves
      (1991, 1992 and 1993) of the nationally representative samples of the general
      population aged > or = 12 interviewed in the National Household Surveys on Drug
      Abuse (n = 87915). An approximation of DSM-IV drug-specific last year dependence
      for each drug class was derived from self-reported symptoms of dependence, data
      on frequency and quantity of use and drug-related problems reported for the last
      year. Descriptive and multivariate analyses were conducted. The inclusion of
      cigarettes among the drugs, the large number of cases and the wide age range of
      respondents (> or = 12) enable us to make drug, age, gender and ethnic
      comparisons not otherwise possible in any other data set. The proxy measure of
      dependence, however, has limitations. The five major findings are that: (1)
      nicotine is the most addictive of the four drugs we examined; (2) among female
      last year users of alcohol and marijuana, adolescents are significantly more at
      risk for dependence than any other age group of women; (3) conditional
      prevalences of last year dependence on alcohol, marijuana and cocaine are higher
      among adolescent females than adolescent males but significantly different only
      for cocaine; (4) among adults, the rates of dependence are higher among males
      than among females for alcohol and marijuana, but lower for nicotine; and (5)
      among last year users, whites are more likely than any other ethnic group to be
      dependent on nicotine and blacks to be dependent on cocaine.

PMID- 9031817
TI  - Antagonism of AND and AND-OR drug mixture discriminations in rats.
AB  - It has been suggested that use of the AND-OR training method may be associated
      with an enhancement of the pharmacological specificity of discriminations based
      on mixture of drugs. Rats were trained to discriminate a mixture of nicotine (0.4
      mg/kg s.c.) plus midazolam (0.2 mg/kg s.c.) from saline (AND-discrimination, n =
      8) or to discriminate the mixture from either drug alone (AND-OR discrimination,
      n = 6). The studies used two-lever operant procedures with food reinforcers
      presented on a tandem schedule. After discriminations were acquired to 80%
      accuracy, the nicotine antagonist mecamylamine (0.03 1.0 mg/kg s.c.) and the
      benzodiazepine antagonist flumazenil (0.32 10 mg kg i.p.) were tested on the
      response to the mixture of nicotine plus midazolam. The antagonist effects of
      either mecamylamine or flumazenil given alone were more marked in rats trained
      under the AND-OR procedure than in rats trained on the AND-discrimination.
      Similarly, the antagonist effects of mixtures of mecamylamine plus flumazenil
      were much more potent under the AND-OR than under the AND-discrimination
      procedure. The AND-OR method reduced the dose of the antagonist mixture needed to
      produce complete block by a factor of about 10, as compared with the AND
      discrimination. These striking differences in sensitivity to antagonists support
      the view that AND-OR or related procedures may enhance the pharmacological
      specificity of complex drug discriminations.

PMID- 9031818
TI  - Gender differences in cocaine dependent patients: a 6 month follow-up study.
AB  - This 6-month follow-up study compared 64 men and 37 women hospitalized for
      cocaine dependence. Drug histories, sociodemographic characteristics, psychiatric
      diagnoses, and Addiction Severity Index (ASI) scores were compared during
      hospitalization; cocaine use and ASI scores were compared at 6 months. During
      hospitalization, women had significantly more severe family and social problems;
      men had more antisocial personality disorder. At follow-up, significantly more
      women had remained abstinent: family/social problem severity no longer differed.
      This replicates previous research showing better treatment outcome for cocaine
      dependent women. This may be related to specific characteristics of women who
      enter mixed-gender cocaine treatment programs.

PMID- 9031820
TI  - Changes in HIV-related behaviors among heterosexual alcoholics following
      addiction treatment.
AB  - In order to measure changes in HIV-related behaviors among heterosexual
      alcoholics following treatment, we conducted a prospective cohort study of 700
      self-identified alcoholics recruited from five public alcohol treatment centers,
      all of which included HIV risk-reduction counseling. Respondents underwent an HIV
      antibody test and interviewer-administered questionnaire at entry to alcohol
      treatment and after a mean of 13 months later. Compared to baseline, at follow-up
      there was an overall 26% reduction in having sex with an injection-drug-using
      partner (23% versus 32%, P < .001) and a 58% reduction in the use of injection
      drugs (15% versus 37%, P < .001), along with smaller improvements in other
      behaviors. Respondents also showed a 77% improvement in consistent condom use
      with multiple sexual partners (35% versus 20%, P < .01) and a 23% improvement in
      partner screening (71% versus 57%, P < .001). Respondents who remained abstinent
      showed substantially greater improvement than those who continued to drink.

PMID- 9031819
TI  - Effects of spinal versus supraspinal administration of cyclic nucleotide
      dependent protein kinase inhibitors on morphine tolerance in mice.
AB  - The consequences of becoming tolerant to the analgesic effects of morphine
      include increased risk of unwanted side effects, such as respiratory depression,
      because the patient is required to take larger doses of the opioid to get the
      same relief from pain. Many studies suggest that phosphorylation plays a role in
      the neuroplasticity associated with opioid tolerance. This study examines the
      effect of inhibiting cyclic nucleotide-dependent protein kinase activity in the
      brain or spinal cord of morphine-tolerant mice. KT5720, a cyclic adenosine
      monophosphate (cAMP)-dependent protein kinase inhibitor, or KT5823, a cyclic
      guanosine monophosphate (cGMP)-dependent protein kinase inhibitor, was centrally
      administered in morphine-tolerant and placebo-treated mice prior to a
      systemically administered challenge dose of morphine. KT5720 completely reversed
      morphine tolerance in the tail-flick assay when the pretreatment was administered
      intracerebroventricularly (i.c.v.); KT5823 had no effect on morphine via this
      route. When either of these drugs was administered intrathecally (i.t.), the
      activity of morphine was greatly diminished in the tolerant animals, with no
      effect on morphine antinociception in the placebo group. These data suggest that
      cAMP-dependent protein kinase activity may be upregulated in the brain with
      morphine tolerance, and that this upregulation is critical to the expression of
      tolerance to the antinociceptive effects of morphine. In the spinal cord,
      however, the activity of cyclic nucleotide dependent protein kinases, and
      possibly their substrate proteins, may be affected by chronic morphine exposure
      such that inhibition of these kinases produces hyperalgesia.

PMID- 9031831
TI  - Overview of screening techniques. Recent advances in prenatal diagnosis for
      aneuploidy.

PMID- 9031821
TI  - Double-blind study of lofexidine and clonidine in the detoxification of opiate
      addicts in hospital.
AB  - Twenty eight opiate addicted inpatients who had been stabilised on methadone took
      part in a double-blind randomised trial of clonidine and lofexidine (14 on each
      treatment) for opiate detoxification: clonidine or lofexidine dosage was titrated
      according to symptoms. The course of withdrawal symptoms was very similar with
      both treatments, representing an appreciable suppression of symptoms when
      compared with experiences of sudden methadone withdrawal, but lofexidine resulted
      in significantly less hypotension and adverse events. These results suggest that
      lofexidine is a valuable drug for opiate detoxification and may be more
      acceptable to patients wishing to withdraw from opiates.

PMID- 9031832
TI  - Ethical aspects of non-invasive prenatal diagnosis: medical, market, or
      regulatory model?

PMID- 9031833
TI  - Risk communication; the patient's view.

PMID- 9031834
TI  - Down's syndrome epidemiology and risk estimation.
AB  - Prenatal screening for Down's syndrome uses a risk estimate as the screening
      variable. Modifying the age-associated risk by measuring biochemical markers or
      fetal measurements requires more sophisticated mathematical techniques than
      calculating the observed estimates of the likelihood ratio. Frequently, the
      screening performance is reported on the same data used to generate the model.
      This can lead to an overestimate of the performance likely to be achievable in
      practice. In order to determine whether a proposed model for screening is better
      (or worse) than an established model, the two should be directly compared on a
      reasonably sized dataset of cases and controls that was not used to derive either
      of the models. At best, only marginal gains in screening performance can be
      expected using new or refined models for assigning Down's syndrome risk.

PMID- 9031835
TI  - Established markers in second trimester maternal serum.

PMID- 9031836
TI  - Second trimester ultrasound markers for fetal aneuploidy.
AB  - Most fetuses with major chromosomal abnormalities have either external or
      internal defects that can be recognized by detailed ultrasonographic examination.
      These are defined as ultrasound markers for fetal chromosomal defects. In case of
      trisomy 13, 18, Turner's syndrome and triploidy, what we would consider as
      ultrasound markers are often major defects. In contrast, in Down's syndrome
      fetuses the structural defects are subtle and often isolated. Ultrasound
      screening programs for this trisomy are based on a systematic search for specific
      markers. Chromosomal anomalies are more common in fetuses with multisystem
      malformation. In fact the risk of a fetal aneuploidy increases with the number of
      detected defects. Other important prognostic factors are maternal age and
      gestational age. For every single structural abnormality it is possible to
      estimate the specific risk of this being a phenotypic expression of a chromosomal
      defect according to whether it is isolated or associated to more structural
      defects. This risk will also be influenced by the maternal age and the
      gestational age.

PMID- 9031837
TI  - Ultrasound screening for fetal trisomies at 10-14 weeks' gestation.

PMID- 9031838
TI  - Prenatal screening for Down syndrome: should first trimester ultrasound replace
      maternal serum screening?

PMID- 9031839
TI  - Urinary analysis for Down's syndrome: is the measurement of urinary beta-core the
      future of biochemical screening for Down's syndrome.
AB  - Most Down's Screening protocols have concentrated on the analysis of oncofetal
      antigen levels present in serum. Urine has largely been ignored, but mass
      screening based on a urine text has several logistical advantages. We have
      examined the levels of urinary beta-core as a marker of Down's syndrome. (beta
      core is a major immunoreactive degradation product of hCG and in particular its
      beta-subunit). Elevated maternal serum hCG is the single most effective
      biochemical marker of Down's syndrome and levels are more than doubled.
      Measurement of elevated free beta-subunit has been shown to be a superior
      discriminator than measurement of intact or total-hCG. This was shown by an
      increase in comparative serum levels from 2.04 to 2.41 multiples of the control
      population medium (MoM). The median MoM value of beta-core for Down's cases in
      studies has varied between 4.38 and 6.28. The proportion of true Down's cases
      having a beta-core value greater than the 95th centile of the controls varied
      from 61 to 93%. This is far superior to any single serum marker. If other
      complimentary urinary markers can be found urinary screening could replace serum
      screening not only because of the logistical advantages but increased
      sensitivity.

PMID- 9031840
TI  - Detection of beta-core fragment in second trimester Down's syndrome pregnancies.

PMID- 9031841
TI  - Quality assessment of a prenatal screening program.
AB  - Epidemiologic monitoring is a process which uses data generated from the screened
      population as a quality control measure. Most commonly, laboratories monitor the
      percentage of women with screen positive test results, i.e., with test results
      falling at or above a specified multiple of the median (MoM) for open neural tube
      defect screening or, with a risk at or above a specified risk cut-off for Down's
      syndrome screening. These percentages are sensitive to inaccurate and imprecise
      assays, inappropriate reference data, and long term assay drift. In fetal Down's
      syndrome screening it is necessary to simultaneously monitor two or more assays,
      which is accomplished by monitoring the median MoM for each assay (which should
      be 1.0 within statistical limits) calculated using patient MoM values. Monitoring
      the median MoM can identify inappropriate adjustment factors for variables which
      affect the MoM such as maternal weight. Epidemiologic monitoring is a useful tool
      for identifying problems which are not readily apparent using traditional quality
      control measures.

PMID- 9031842
TI  - The diagnostic value of the triple test in the diagnosis of Down's syndrome.

PMID- 9031843
TI  - Detection rates and false positive rates for Down syndrome screening: how
      precisely can they be estimated?

PMID- 9031844
TI  - The significance of placental pathology in pregnancies with unexplained abnormal
      concentrations of MSAFP or MShCG.

PMID- 9031845
TI  - The pathophysiology of Down's syndrome pregnancies.

PMID- 9031846
TI  - Specific approaches to fetal cells isolation from maternal blood: introduction.

PMID- 9031847
TI  - Application of PCR for fetal cell detection.

PMID- 9031848
TI  - Isolation of fetal trophoblasts and nucleated erythrocytes from the peripheral
      blood of pregnant women for prenatal diagnosis of fetal aneuploides.
AB  - We present the results of a study of fetal cell isolation from the peripheral
      blood of 46 women in the first trimester of pregnancy. The trophoblasts were
      sorted with paramagnetic beads labelled with a novel monoclonal antibody 340
      (Mab340) (Durrant et al., Prenat. Diagn., 14 (1994) 131). This was followed by
      triple density gradient enrichment to remove maternal lymphocytes and red blood
      cells. Nucleated red blood cells (NRBC) were sorted by incubation with
      ferromagnetic particles coated with Mab CD71, an antitransferrin receptor
      monoclonal antibody, and separation on a mini-MACS column. Sorted cells were
      sexed using nested PCR for the Y chromosome and the results compared with the
      karyotypic analysis of the CVS. The sensitivity in determining a male pregnancy
      with NRBC alone was 38% and with trophoblasts alone was 39%. Sorting for both
      cell types correctly predicted a male pregnancy in 10/18 or 56%. Of the 10 males
      correctly identified, 3 were diagnosed on NRBC alone, 3 on trophoblast alone and
      4 with both cell types. As there are very few fetal cells in maternal blood,
      sorting for both will increase the yield and improve diagnosis. However the
      technique requires further development to improve sensitivity.

PMID- 9031849
TI  - Isolation and genetic analysis of fetal nucleated red blood cells from maternal
      blood: the Baylor College of Medicine experience.

PMID- 9031850
TI  - Detection of 'rare event' fetal erythroblasts in maternal blood using automated
      microscopy.
AB  - This paper describes the use of automated microscopy to detect fetal
      erythroblasts in maternal blood. The technology is based on the following
      approach: (1) the use of centrifugal cytology for the preparation of monolayers;
      (2) simultaneous staining of fetal hemoglobin (immunoalkaline phosphatase) and
      chromosome sequences (FISH); (3) multi-mode microscopy to detect rare events; (4)
      visual evaluation of image memories containing detected objects. Model systems
      show that fetal cells in frequencies as low as 1 in a million cells can be
      detected easily (manually or by automated microscopy). Algorithms for automated
      cell selection were developed for a test set of 6 patients. Optimization of
      hardware and software routines will make analysis of several million cells in
      approximately 1 h feasible.

PMID- 9031851
TI  - Detection of fetal erythroblasts in maternal blood by one-step gradient
      enrichment and immunocytochemical recognition.

PMID- 9031852
TI  - Reliability of trans-cervical recovery of placental cells from the lower uterine
      pole using a minimally invasive procedure. Evidence based on fetal sexing and
      analysis of recovered cell populations.
AB  - OBJECTIVE: Efficient recovery of placental cells (and their subsequent
      characterisation) from the lower uterine pole (L.U.P) by trans-cervical flushing
      or aspiration. SUBJECTS: Women attending for termination of pregnancy (7-17
      weeks' gestation) for social reasons. All patients gave their consent to the
      procedures outlined below. METHODS: Trans-cervical intrauterine flushing (using
      0.15 M NaCl) or mucus aspiration. Embryo transfer catheters were used in both
      procedures. Fetal sexing was achieved by gene amplification of Y-specific DNA
      sequences (Y-PCR), and by in situ hybridisation (bright-field and fluorescence)
      to the Y-chromosome. Data were compared with results obtained from fetal tissues
      recovered following termination of pregnancy. Gender-independent tests for fetal
      cells utilised immunocytochemistry with trophoblast-specific antibodies and dual
      immunocytochemistry/ISH, where appropriate. RESULTS: (1) Fetal sexing by Y-PCR:
      71/122 (58%) aspirates contained Y-specific DNA. In addition, the sexing of 72/86
      (84%) aspirates and their corresponding samples of placental tissue, agreed
      exactly. (2) Microscopic detection of fetal cells. Placentally-derived
      syncytiotrophoblast was detected in 17/45 (38%) flushings and 39/173 (23%)
      aspirates. In most other Y-PCR+ samples which were negative for
      syncytiotrophoblast, Y-chromosome-bearing nuclei of unknown origin, were observed
      by ISH and immunocytochemical evidence for cytotrophoblastic cells was also
      uncovered. CONCLUSIONS: Since Y-derived DNA can be detected in > 50% of flushings
      and aspirations, and gender-independent evidence for placental cells was
      obtained, regardless of fetal sex, we believe that most or all of these samples
      contained placental cells, including trophoblasts and naked nuclei. Trans
      cervical placental cell recovery is a potentially valuable alternative to more
      invasive methods of aneuploid detection which require amniocentesis and CVS,
      provided its level of accuracy and above all, safety, can be evaluated.

PMID- 9031853
TI  - Early prenatal diagnosis of fetal aneuploidy using coelomic fluid.

PMID- 9031854
TI  - Markers for Down's syndrome in early pregnancy.

PMID- 9031855
TI  - Ammonia and encephalopathy in the horse.

PMID- 9031856
TI  - Viable aneuploidy in the horse.

PMID- 9031858
TI  - Chronic tenosynovitis of the carpal extensor tendon sheaths in 15 horses.
AB  - The history, clinical features, radiological findings, treatment and outcome of
      15 horses with chronic tenosynovitis of the carpal extensor tendon sheaths are
      reported. The condition was seen most commonly in horses used for jumping and
      penetration of the tendon sheaths by thorns was the most common aetiology.
      Treatment involved surgical resection of the hyperplastic synovial membrane, and
      adhesions within the tendon sheath, with primary closure. When combined with
      early postoperative physiotherapy this was found to be an effective method of
      treatment. All horses in this series were not lame at follow-up, with 14 horse
      returning to their former level of athletic performance.

PMID- 9031857
TI  - Cardiorespiratory responses to exercise in horses with different grades of
      idiopathic laryngeal hemiplegia.
AB  - The relationship between different grades of laryngeal function, as assessed by
      endoscopy at rest, and the measurements of indices of gas exchange and exercise
      capacity was assessed during a standardised treadmill exercise test in 149
      horses. Horses with abnormalities other than idiopathic laryngeal hemiplegia
      (ILH) were excluded from the study and laryngeal function was graded according to
      an established system. There were no significant differences in age, weight,
      maximum oxygen uptake, maximum carbon dioxide production, maximum respiratory
      exchange ratio, maximum oxygen pulse and run time between the grades. Blood
      lactate concentration at 10 m/s was greater (P < 0.01) in horses with grade 5
      laryngeal function than other grades. Minimum PaO2 (P < 0.001) and SaO2 (P <
      0.01) were lower and maximum PaCO2 (P < 0.001), higher in horses with grades 4
      and 5 laryngeal function than other grades. Horses with grade 4 function had a
      lower minimum CaO2 (P < 0.01) than horses with other grades. Minimum PAO2
      decreased from grades 1 and 2 to grades 4 and 5 (P < 0.05). The minimum alveolar
      ventilation was lower (P < 0.05) in horses with grades 4 and 5 laryngeal function
      compared to other grades. The results of this study indicate that endoscopic
      assessment of laryngeal function at rest, using a simple grading system, provides
      an indication of dynamic changes in ventilation and the effects on blood gases
      during exercise. From the data, we suggest that horses that have some movement of
      the left arytenoid cartilage but are unable to achieve full abduction have
      similar ventilatory effects and blood gas responses during maximal exercise to
      those with complete paralysis. Some horses with grade 3 laryngeal function had
      blood gas results similar to those of horses with grades 4 and 5 laryngeal
      function, indicating that discrepancies may occur between the resting assessment
      and laryngeal function during strenuous exercise.

PMID- 9031859
TI  - Measurement of cardiac output in standing horses by Doppler echocardiography and
      thermodilution.
AB  - Measurement of cardiac output by Doppler echocardiography were compared to
      simultaneous measurements by thermodilution in 9 conscious horses. In the Doppler
      technique, mean blood flow velocities for estimation of cardiac output were
      recorded from the aorta and pulmonary artery. The flow area of each vessel was
      calculated from the vessel diameter, measured from a 2-dimensional ultrasound
      image. Differences in the site and method of measuring the vessel diameter
      altered the estimation of cardiac output by the Doppler method. Cardiac output
      was modified by the i.v. infusion of 4 micrograms/kg bwt/min dopamine and 4
      micrograms/kg bwt/min dobutamine and by the i.v. administration of 10
      micrograms/kg bwt detomidine and 20 micrograms/kg bwt butorphanol. Doppler
      measurements of cardiac output correlated closely with measurement by
      thermodilution. Measurements from the aortic outflow correlated more closely with
      thermodilution, than those from the pulmonary artery (r = 0.89 and r = 0.77,
      respectively). Doppler measurements when the mean flow velocity was recorded from
      the aorta and the flow area was measured from the ascending aorta using the
      leading edge method. There was no significant bias between the 2 techniques when
      Doppler flow velocities were recorded by this method and the limits of agreement
      were narrow (+/- 12.26 l/min). The differences between the 2 methods increased
      with increasing cardiac output. Doppler echocardiography is a safe noninvasive
      method of measuring cardiac output in horses. The agreement between Doppler
      echocardiography and thermodilution in this study is similar to that reported in
      man and is similar to that reported between thermodilution and other techniques
      in man.

PMID- 9031860
TI  - Radiation hazards from horses undergoing scintigraphy using technetium-99m.
AB  - This paper quantifies the extent of the radiation hazard to personnel from horses
      undergoing scintigraphy using technetium99m methylene diphosphonate (99Tcm-MDP).
      From the data produced it is possible to derive safe working protocols which are
      comfortably within the legislated limits for whole body doses as set out in the
      Ionising Radiations Regulations 1985. Measurements were made of the surface and
      environmental activities which result from individuals undergoing scintigraphic
      evaluation and also from urine contaminated bedding. The use of both high and low
      activities in the assessment of the radiation hazard to personnel and owners is
      considered.

PMID- 9031861
TI  - Visual outcome and ocular survival following iris prolapse in the horse: a review
      of 32 cases.
AB  - The medical records of 32 horses treated for iris prolapse (IP) during an 8 year
      period, at the University of Florida Veterinary Medical Teaching Hospital, were
      reviewed. Iris prolapse was associated with perforated corneal ulcers in 15
      horses (47%), ruptured stromal abscesses in 2 horses (6%), and full thickness
      corneal lacerations in 15 horses (47%). Initial ophthalmic examinations revealed
      IP with severe iridocyclitis in all eyes and keratomalacia in 8 eyes with corneal
      ulcers, one with a stromal abscess and 1 with a corneal laceration. Hyphema was
      present in 7 eyes with corneal lacerations. Thirty horses were managed with
      combined medical and surgical therapy. Two horses were only treated medically
      with topically administered antibiotics. Of the 24 perforations surgically
      repaired, 21 were closed primarily and 13 were then covered with a conjunctival
      graft. After combined therapy and a minimum of 4 months of follow-up, vision was
      retained in 6 of the horses (40%) with perforating corneal disease and 5 of the
      horses (33%) with perforating corneal lacerations. Post operatively, of the 11
      (37%) horses blind at discharge, 6 (55%) subsequently developed phthisis bulbi.
      Enucleations were performed in 4 cases with extensive keratomalacia and/or
      endophthalmitis, 2 cases with limbal rupture and total hyphema, and one case with
      a chronic IP. One horse was subjected to euthanasia after 3 surgical treatments
      failed to stabilise stromal melting. Horses presented with ulcerative keratitis
      of fewer than 15 days duration, or horses with corneal lacerations less than 15
      mm in length, tended to have a favourable visual outcome. Keratomalacia, hyphema,
      corneal lacerations longer than 15 mm and lacerations extending to, along, or
      beyond the limbus, adversely influenced visual outcome. Iridectomy did not appear
      clinically to exacerbate anterior uveitis or adversely affect visual outcome.
      Ocular survival following combined therapy was 80% (12/15) in horses with corneal
      lacerations and 67% (10/15) in horses with ulcerative keratitis.

PMID- 9031862
TI  - A survey for antibodies to equine arteritis virus in donkeys, mules and zebra
      using virus neutralisation (VN) and enzyme linked immunosorbent assay (ELISA).
AB  - A seroepidemiological survey of donkeys in South Africa (n = 4300) indicated a
      wide distribution and increasing prevalence of antibodies to equine arteritis
      virus (EAV). Donkey sera inhibited equine arteritis virus infection in virus
      neutralisation (VN) tests and in ELISA specifically bound to a recombinant
      antigen derived from the Bucyrus isolate of EAV. These results suggest that
      donkeys have been exposed to the same serotype of this virus as circulates among
      horses. A good correlation existed between EAV neutralising antibody titres and
      ELISA absorbance values (0.8631); the ELISA was sensitive and specific (99.2% and
      80.3% respectively) for donkey sera when compared to the VN test and the
      recombinant ELISA antigen did not cross-react with sera positive for common
      African equine pathogens. VN+ ELISA+ donkeys were also found in Morocco and
      Zimbabwe and seropositive mules in both South Africa and Morocco. No seropositive
      zebra (n = 266) were detected from game reserves or zoos in 9 countries. The
      results confirm that in addition to horses and donkeys, mules are naturally
      infected with EAV.

PMID- 9031863
TI  - Relationship between ossification of the cartilages of the foot and conformation
      and radiographic measurements of the front feet in Finnhorses.
AB  - One hundred Finnhorse cadaver front feet were measured and examined both
      radiographically and visually to report the incidence of various foot problems
      and their relationship to ossification of the cartilages of the foot.
      Ossification extending above the proximal border of the navicular bone and/or
      separate centres of ossification were found in 36 feet, and the lateral
      cartilages showed more ossification than the medial cartilages. The feet were
      generally broad with well developed frogs, but the long toe-low heel syndrome was
      a relatively common finding. Ossification of the cartilages correlated with the
      length of the heels but was not related to any clinically significant foot
      abnormalities such as contracted or under-run heels or signs of unequal
      weightbearing. Ossification of the cartilages did not seem to be either the cause
      or the result of general conformational adaptations of the front feet.

PMID- 9031864
TI  - Flexion test of the metacarpophalangeal and interphalangeal joints and flexion
      angle of the metacarpophalangeal joint in sound horses.
AB  - This paper describes the application of a measuring device 'Flextest' to control
      the effect of traction force and traction time during flexion tests of the distal
      limb joints of the forelimbs. The optimal force for a flexion test is 100 N, over
      1 min. A higher force (150 N) was not harmful. A slightly positive flexion
      response (100 N/1 min) in a horse with no other clinical signs or radiographic
      abnormalities is not of clinical significance. Individual left and right flexion
      and extension angles are almost identical and do not depend on age. Stabled
      horses which have been rested or horses resting at pasture are less likely to
      have a positive flexion test than working horses.

PMID- 9031865
TI  - The significance of routine radiographic findings with respect to subsequent
      racing performance and longevity in standardbred trotters.
AB  - A retrospective cohort study was made of the racing performance of trotters which
      had been subjected routinely to radiography before they started training and
      racing. Sixty-one per cent (148) of the 243 horses, foaled in 3 consecutive
      years, had one or more abnormal findings categorised into 5 relevant groups based
      on radiography, of which osteochondrosis (OCD) was the most specific diagnosis.
      Parameters used to reflect racing performance were: proportion of horses starting
      in races, number of starts per year, earnings per year, earnings per start and
      racing longevity. No significant association between the presence or type of
      radiological abnormalities and the subsequent performance and longevity could be
      found. Horses with multiple lesions, however, had a tendency to lower earnings
      and poorer survival than horses with single lesions.

PMID- 9031866
TI  - Arthrogryposis in the foal and its possible relation to autosomal trisomy.

PMID- 9031867
TI  - Radiographic features of mastocytosis in the equine limb.

PMID- 9031868
TI  - A cross-sectional epidemiological study of equine hoof wall problems and
      associated factors.

PMID- 9031869
TI  - Hyperammonaemia associated with encephalopathy and abdominal pain without
      evidence of liver disease in four mature horses.

PMID- 9031870
TI  - Complete upper airway obstruction and syncope caused by a subepiglottic cyst in a
      horse.

PMID- 9031871
TI  - Chylothorax and meconium impaction in a neonatal colt.

PMID- 9031872
TI  - Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch
      university hospitals.
AB  - The aim of this study was to identify retrospectively trends in fungal
      bloodstream infections in The Netherlands in the period from 1987 to 1995.
      Results of over 395,000 blood cultures from five Dutch university hospitals were
      evaluated. Overall, there were more than 12 million patient days of care during
      the nine-year study period. The rate of candidemia doubled in the study period,
      reaching an incidence of 0.71 episodes per 10,000 patient days in 1995. The
      general increase in candidemia was paralleled by an increase in non-Candida
      albicans bloodstream infections, mainly due to Candida glabrata. However, more
      than 60% of the infections were caused by Candida albicans. Fluconazole-resistant
      species such as Candida krusei did not emerge during the study period. The
      increasing rate of candidemia found in Dutch university hospitals is similar to
      the trend observed in the USA, but the rate is lower and the increase is less
      pronounced.

PMID- 9031873
TI  - Risk factors leading to clinical failure in the treatment of intra-abdominal or
      skin/soft tissue infections.
AB  - A study of determinants of outcome in adult patients with intra-abdominal or
      skin/soft tissue infections treated with cefotetan, cefoxitin, or
      ampicillin/sulbactam monotherapy was undertaken. Patients were matched for
      principal infectious process, surgery performed for the management of the
      infection, year of hospital admission, age, and sex. The criteria for inclusion,
      exclusion, and matching of patients and assignment of clinical and
      microbiological outcome were based on the 1992 Infectious Diseases Society of
      America/Federal Drug Administration guidelines for the evaluation of anti
      infective drug products. One hundred and thirty-seven cases of intra-abdominal or
      skin and soft tissue infections treated with cefotetan (n = 47), cefoxitin (n =
      43), or ampicillin/sulbactam (n = 47) monotherapy were selected without knowledge
      of outcome and analyzed using a single blinded analysis. The baseline
      characteristics did not differ between the treatment groups, nor did the rates of
      clinical or microbiological failure. A multivariate analysis showed that
      isolation of an organism resistant to the treatment regimen, including
      Pseudomonas spp., [odds ratio (OR) = 14.9, p = 0.001], being on antibiotic
      therapy at the time of admission (OR = 4.5, p = 0.007), and diagnosis of a
      complicated intra-abdominal infection (OR = 3.5, p = 0.014) were independently
      associated with clinical failure. These data support the assertion that
      antibiotic resistant organisms in mixed anaerobic/aerobic infections are
      associated with clinical failure and suggest that the antibiotic regimen should
      be modified to include Pseudomonas spp. in its spectrum when this organism is
      isolated from patients with such infections.

PMID- 9031874
TI  - Performance of six culture media for isolation of Salmonella species from stool
      samples.
AB  - The relative performance of five plating media [Rambach agar; salmonella-shigella
      (SS) agar, novobiocin-brilliant green-glycerol-lactose (NBGL), modified semisolid
      Rappaport-Vassiliadis medium (MSRV), and Salmonella Detection and Identification
      2 (SM2)] and selenite broth (SB) subcultured in SS agar in the recovery of
      Salmonella spp. from 500 human stool specimens was evaluated. On Rambach agar and
      SS agar, the C8-esterase test was also used for selection of suspicious colonies.
      Eighty-one samples were positive for salmonellae on at least one of the six
      media. Sensitivities and specificities of MSRV, SB, NBGL, SS, Rambach agar, and
      SM2 were 95.1 and 98.1%, 87.6 and 99.8%, 79 and 91.9%, 69.1 and 99.3%, 56.8 and
      96.9%, and 54.3 and 92.4%, respectively. There were statistically significant
      differences between MSRV and NBGL, Rambach agar, SS agar, and SM2 (p < 0.005),
      between SB and SS agar, Rambach agar, and SM2 (p < 0.05), and between NBGL and
      SM2 and Rambach agar (p < 0.005). The greatest number of isolates was recovered
      with MSRV, whose performance surpassed that of enrichment in selenite broth,
      probably because the subcultures were not repeated on MSRV. This hypothesis is
      now under investigation. The specificity of each of the five solid media was
      greater than 90%.

PMID- 9031875
TI  - Comparative safety and immunogenicity of an acellular versus whole-cell pertussis
      component of diphtheria-tetanus-pertussis vaccines in Senegalese infants.
AB  - A diphtheria and tetanus toxoid two-component acellular pertussis vaccine (DTaP),
      consisting of 25 micrograms glutaraldehyde-detoxified pertussis toxin (PT) and 25
      micrograms native filamentous hemagglutinin (FHA), was compared with diphtheria
      and tetanus toxoid whole-cell pertussis vaccine (DTwP) in a randomized, double
      blind manner in 286 Senegalese infants inoculated at two, four, and six months of
      age. In infants receiving DTaP a significantly lower rate of local reactions,
      crying and fever was observed than in infants receiving DTwP. One month after the
      third dose, the geometric mean titres for FHA antibodies were higher in the DTaP
      group, whereas increases in PT antibody titres were higher in the DTwP group.
      More than 90% of the infants had a fourfold or more increase in antibodies to
      both PT and FHA with either vaccine. Diphtheria, tetanus, and polio antibody
      responses were also measured and found to be comparable between the two groups.
      The results of this pilot study support the implementation of a field trial to
      compare the protective efficacy of these vaccines against pertussis in the same
      setting.

PMID- 9031876
TI  - In vitro study of the potential role of quinupristin/dalfopristin in the
      treatment of catheter-related staphylococcal infections.
AB  - The susceptibility of clinical isolates of methicillin-susceptible and -resistant
      staphylococci from cancer patients with central venous catheter bacteremia to
      quinupristin/dalfopristin, a semisynthetic streptogramin, was determined in
      vitro. Susceptibility of these isolates to nine other antistaphylococcal
      antibiotics was also determined for comparison. A total of 197 staphylococcal
      strains were tested from 1983 to 1992. Quinupristin/dalfopristin was bactericidal
      against all isolates, independent of their resistance to methicillin. Its
      activity was similar to that of vancomycin but superior to that of teicoplanin.
      Quinupristin/dalfopristin may prove to be an important addition to our
      armamentarium against catheter-related staphylococcal infections.

PMID- 9031877
TI  - In vitro activity of omeprazole in combination with several antimicrobial agents
      against clinical isolates of Helicobacter pylori.
AB  - An agar dilution checkerboard method was used to evaluate the in vitro activity
      of omeprazole combined with clarithromycin, amoxicillin, and ceftibuten,
      respectively, against clinical isolates of Helicobacter pylori. Mueller-Hinton
      agar plus 5% horse blood, an inoculum of 10(6) cfu/ml, and incubation of 72 h in
      a CO2 atmosphere were used. With the omeprazole and clarithromycin combination,
      synergism was observed in 51.5% and partial synergism in 39.3% of 33 strains;
      with omeprazole and amoxicillin, synergism was observed in 3% and partial
      synergism in 60.6% of 33 strains; and with omeprazole and ceftibuten, synergism
      was observed in 33.3% and partial synergism in 50% of 24 strains. Antagonism
      between omeprazole and each antibiotic was exhibited in 0%, 6.1%, and 4.1% of
      these groups of strains, respectively. Of the antibiotic combinations tested,
      omeprazole plus clarithromycin exhibited synergism (partial or total) in the
      highest percentage of strains.

PMID- 9031878
TI  - Ceftibuten concentrations in human tonsillar tissue.
AB  - In a study designed to determine ceftibuten concentrations in tonsillar tissue,
      subjects scheduled to undergo tonsillectomy were administered 400 mg of
      ceftibuten in a single oral dose. Between 2 and 24 h after the dose was given,
      tonsillar tissue samples were taken during surgery and assayed for ceftibuten.
      Mean concentrations in tonsillar tissue 4.4 h and 24.6 h after the 400 mg dose
      were 5.3 +/- 2.7 and 0.3 +/- mg/g, respectively. Concurrent mean serum
      concentrations were 7.42 +/- 1.66 and 0.15 +/- 0.13 mg/ml, respectively. The
      apparent half-life of drug in the tissue was 5.3 h. The presence of high
      ceftibuten concentrations in tonsillar tissue suggests that a once-daily regimen
      may be effective in treating tonsillitis and pharyngitis.

PMID- 9031879
TI  - Western blot monitoring of disseminated Nocardia nova infection treated with
      clarithromycin, imipenem, and surgical drainage.
AB  - A case of disseminated infection due to Nocardia nova with subcutaneous popliteal
      and retrosternal abscesses and lung involvement in an immunocompromised patient
      is reported. The patient did not respond to sulfonamide therapy. Clinical
      recovery was obtained upon treatment with imipenem then clarithromycin. Western
      blot studies revealed an antibody response to a known Nocardia-specific 55-kDa
      antigen in four successive sera samples collected in the period from the time of
      admission to seven months later. The resolution of the disseminated nocardiosis
      and efficacy of the clarithromycin treatment were assessed on the basis of
      disappearance of the antibodies to the 55-kDa antigen, without invasive sampling.

PMID- 9031880
TI  - Characterisation of atypical biotype 3, serotype O:3 Yersinia and development of
      a simple identification scheme.
AB  - Five clinical strains of Yersinia isolated in Japan and identified as atypical
      biotype 3 or biotype 3B, serotype O:3, phage type II (3*/O:3/II) Yersinia
      enterocolitica were characterised since the biochemical reactions of these
      strains indicate they might also belong to the species Yersinia bercovieri.
      Biochemical tests, characterisation of the beta-lactamases and DNA-DNA
      hybridization studies provided strong evidence indicating that these strains
      should be classified as Yersinia enterocolitica. A simple scheme combining a disc
      diffusion test and four biochemical tests was devised for identification of these
      atypical strains.

PMID- 9031881
TI  - Prevalence of Dientamoeba fragilis antibodies in children and recognition of a 39
      kDa immunodominant protein antigen of the organism.
AB  - Dientamoeba fragilis, a common intestinal protozoan parasite in Canada, has been
      associated with diarrhoea and abdominal pain in some patients. Seroprevalence of
      this organism has not been reported previously. In the present study sera from
      three symptomatic patients, 12 age- and sex-matched controls, and 189 randomly
      selected healthy individuals (age 6 months to 19 years) were tested for
      antibodies against Dientamoeba fragilis by an indirect immunofluorescence (IIF)
      assay. All three symptomatic patients infected with Dientamoeba fragilis had
      positive IIF titres of 80, and all 12 matched controls had positive titres
      ranging 20 to 160 (geometric mean titre 48). Of the 189 healthy children, 172
      (91%) were positive at a serum dilution of 1:10 or higher. The specificity of the
      IIF assay was reinforced by immunoblotting 20 representative serum samples
      against Dientamoeba fragilis. In all 17 IIF-positive serum samples, a 39 kDa
      protein band of Dientamoeba fragilis was identified, the same band recognized by
      a mouse monoclonal antibody raised in our laboratory. Findings over a five-year
      period indicate that Dientamoeba fra-gilis was the most common protozoan,
      followed closely by Giardia lamblia and more distantly by Cryptosporidium parvum.
      The high seropositivity of 91% for Dientamoeba fragilis compares reasonably well
      with serologic data obtained by IIF and reported previously for Giardia lamblia
      (85.6%) and Cryptosporidium parvum (86%).

PMID- 9031882
TI  - Detection of parvovirus B19 in skin biopsy, serum, and bone marrow of a patient
      with fever, rash, and polyarthritis followed by pneumonia, pericardial effusion,
      and hepatitis.
AB  - A previously healthy 33-year-old male patient presented with fever, rash and
      polyarthritis. Subsequently, he developed pleuropneumonitis, pericardial effusion
      and hepatitis. The diagnosis of parvovirus B19 infection was based on the
      detection of parvovirus DNA by PCR in a skin biopsy, bone marrow cells and serum.
      The patient had high parvovirus IgG antibody titres but remained negative for IgM
      at a three month follow-up, suggesting persistence of the virus or reinfection.
      It is concluded that detection of viral DNA is needed to verify a parvovirus B19
      infection even in an immunologically healthy host.

PMID- 9031883
TI  - Influence of CD4+ status on the invasiveness of pneumococcal pneumonia in HIV
      patients.

PMID- 9031884
TI  - Agrobacterium radiobacter pneumonia in a patient with HIV infection.

PMID- 9031886
TI  - Catalase-negative Listeria monocytogenes causing lethal sepsis and meningitis in
      an adult hematologic patient.

PMID- 9031885
TI  - Native valve endocarditis due to Corynebacterium striatum.

PMID- 9031887
TI  - Diagnosis of visceral leishmaniasis in HIV-infected patients.

PMID- 9031888
TI  - Current European concepts in the management of Helicobacter pylori infection--the
      Maastricht Consensus Report. The European Helicobacter Pylori Study Group
      (EHPSG).

PMID- 9031889
TI  - Transjugular intrahepatic portosystemic shunting (TIPS): a shunt is a shunt is a
      shunt!

PMID- 9031890
TI  - Dyspepsia world-wide and the role of stress.

PMID- 9031891
TI  - Therapeutic modalities in portal hypertension.
AB  - Optimal medical management is with octreotide or terlipressin (Glypressin) for
      acute variceal bleeding and combined beta-blocker and nitrate prophylaxis for
      prevention of rebleeding. Injection sclerotherapy is necessary to arrest acute
      bleeding, with variceal banding preferred for the obliteration of large varices.
      Transjugular intrahepatic portosystemic shunts (TIPS) are best used for
      uncontrolled or recurrent bleeding episodes which fail to respond to endoscopic
      or drug therapy. They can also rarely be used to treat refractory ascites.
      Surgical portosystemic shunting and devascularization techniques have now been
      superseded. Hepatic transplantation should be considered where overall hepatic
      function is poor.

PMID- 9031892
TI  - Mortality after gastric surgery for peptic ulceration.

PMID- 9031893
TI  - Clinical outcome two years after implantation of a transjugular intrahepatic
      portosystemic shunt for recurrent variceal bleeding.
AB  - OBJECTIVE: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS)
      is a relatively new therapy for variceal bleeding. The aim of this study was to
      assess clinical course 2 years after TIPS procedure. DESIGN: The study was
      designed as a prospective, uncontrolled cohort study. METHODS: Forty-six patients
      who underwent successful TIPS implantation were followed prospectively by
      clinical examinations, duplex sonography and portal venography. Mean follow-up in
      surviving patients was 24.1 +/- 9.0 months. RESULTS: The cumulative rate of
      survival was 80.4% at 1 year and 70.2% at 2 years. The cumulative rebleeding rate
      was 12.4% at 1 year and 21.3% at 2 years. The mortality rate of episodes of
      variceal rebleeding was 22.2%. Variceal rebleeding was associated with shunt
      abnormalities, and successful shunt revision resulted in control of the bleeding.
      The cumulative incidence of shunt stenosis or occlusion was 41.2% at 1 year and
      54.9% at 2 years. Of those patients without shunt abnormalities after 1 year,
      23.3% developed shunt stenosis or occlusion during the second year after TIPS
      procedure. Shunt revision was successful in 96.6% of cases. Secondary patency
      rate was 88.1% after 2 years. CONCLUSION: Successful TIPS implantation results in
      a low rate of morbidity and mortality from variceal rebleeding over 2 years. TIPS
      creation in combination with careful follow-up examinations represents an
      effective long-term treatment of recurrent variceal bleeding. Even in patients in
      whom no shunt abnormality is detected during the first year, routine duplex
      follow-up examinations should be continued at 3-month intervals.

PMID- 9031894
TI  - Life events stress in functional dyspepsia: a case control study.
AB  - OBJECTIVE: To study the possible relationship between life-events stress and
      functional dyspepsia. DESIGN: Prospective and case-control study. Exclusion of
      obvious organic disease for the dyspepsia. METHODS: Life-events stress scale;
      derived from life-events scale by Tennant and Andrews. Upper gastrointestinal
      endoscopy and abdominal sonography. RESULTS: There were no significant
      differences between the patients and controls in relation to the number and
      categories of life events. Significant differences, however, were noticed in
      relation to experiencing individual life events, but the interpretation of these
      differences is not clear-cut, as they were present in both patients and controls.
      CONCLUSION: The question of the relationship between the stress and functional
      dyspepsia remains unresolved and further quantitative studies are needed before
      reaching a final conclusion.

PMID- 9031895
TI  - Pentoxifylline, a drug with rheological effects, decreases portal pressure in an
      experimental model of cirrhosis.
AB  - OBJECTIVE: To evaluate the influences of blood viscosity changes, mediated by a
      haemorheological agent, on splanchnic and systemic haemodynamic parameters in
      rats with cirrhosis due to chronic bile duct ligation. METHODS: Blood viscosity
      was measured using a cone-plate viscometer and whole blood filterability was
      determined by a filtration method. Cardiac index and portal venous inflow were
      measured using radioactive microspheres. Measurements were performed 30 min after
      double-blind administration of placebo or pentoxifylline (25 mg/kg,
      intravenously). RESULTS: As compared with placebo, pentoxifylline-treated
      cirrhotic rats had a lower portal pressure (13.8 +/- 1.4 vs. 12.1 +/- 1.6 mmHg, P
      < 0.05) and blood viscosity at shear rates of 115/s (6.6 +/- 0.8 vs. 5.8 +/- 0.3
      mPas, P < 0.05), associated with an improvement of whole blood filterability
      (45.0 +/- 12.9 vs. 20.0 = 3.9 s/ml, P < 0.01). Similar values of mean arterial
      pressure, cardiac index and portal venous inflow were observed in both groups. A
      significant correlation was found between portal pressure and blood viscosity at
      a shear rate of 115/s (r = 0.71, P < 0.01). CONCLUSION: These results suggest
      that portal pressure can be modified by pentoxifylline in an experimental model
      of cirrhosis. These haemodynamic changes are associated with a lower blood
      viscosity and whole blood filterability. Pentoxifylline may be a new approach in
      the treatment of portal hypertension.

PMID- 9031896
TI  - The significance of ulcer disease on late mortality after partial gastric
      resection.
AB  - OBJECTIVE: To study the causes of long-term mortality after peptic ulcer surgery
      with special attention to the impact of underlying ulcer disease. DESIGN:
      Retrospective cohort investigation. PATIENTS: A cohort of 1305 patients who had
      surgery for gastric and duodenal ulcer disease 29 to 59 years ago. At the end of
      follow-up 80% of gastric ulcer patients, and 64% of duodenal ulcer patients were
      dead. RESULTS: Overall mortality was significantly higher among gastric ulcer
      patients: standardized mortality ratio (SMR) 1.17 (95% confidence interval (CI)
      1.05-1.29); duodenal ulcer patients had an overall mortality comparable to the
      reference population: SMR 1.06 (CI 0.97-1.15). Excess mortality among gastric
      ulcer patients was found to be due to neoplasms in gastrointestinal organs (SMR
      1.54 (CI 1.11-2.11) which developed more than 20 years postoperatively, and to
      respiratory diseases and suicide unrelated to time since surgery. An increased
      mortality due to malignant tumours, respiratory diseases and suicide was also
      found among duodenal ulcer patients but this increased mortality was offset due
      to a significantly decreased mortality in diseases of the heart and vascular
      system (SMR 0.86 (CI 0.75-0.97)), evident mainly after 20 years postoperatively.
      Excess mortality due to gastrointestinal cancers outnumbered excess mortality
      from carcinomas in the respiratory organs, and was due to cancers in the stomach,
      colon and pancreas. CONCLUSION: An increased mortality due to gastrointestinal
      carcinoma, especially gastric and pancreatic carcinoma, is apparent regardless of
      underlying ulcer disease. As preventive measures against these tumours have
      yielded little benefit in prospective trials, and as smoking-related diseases and
      tumours together with suicide constitute 75% of the excess mortality, measures to
      combat smoking and suicide might be more worthwhile to reduce mortality in this
      cohort.

PMID- 9031897
TI  - Previous use of non-steroidal anti-inflammatory drugs and anticoagulants: the
      influence on clinical outcome of bleeding gastroduodenal ulcers.
AB  - OBJECTIVE: To evaluate the relationship between prior non-steroidal anti
      inflammatory drug (NSAID) or anticoagulant use and clinical outcome in bleeding
      gastric and duodenal ulcer patients. DESIGN: Prospective cohort-study.
      PARTICIPANTS: All patients (n = 132) admitted because of upper gastrointestinal
      bleeding during 3 months in the Amsterdam area. METHODS: We compared clinical
      outcome (blood transfusion, rebleeding, surgery and mortality) between ulcer
      patients who used NSAIDs or anticoagulants and patients who did not use these
      drugs before the bleeding-episode. RESULTS: Of the 132 patients admitted, 56
      patients had gastric or duodenal ulcers. NSAIDs were used significantly more
      often before the bleeding episode in these ulcer patients than in the non-ulcer
      patients (n = 76), 21/56 (37.5%) vs. 15/76 (19.7%), respectively (P < 0.05),
      relative risk = 2.57, 95% confidence interval: 1.04-5.77). Stigmata of recent
      haemorrhage were found in 16/21 (76.2%) patients in the NSAID ulcer group, in 2/9
      (22.2%) in the coumarin-ulcer patients, and in 12/24 (50%) in the no-medication
      ulcer group (not significant). Prior NSAID usage increased the in-hospital
      rebleeding rate from 16.7% to 42.9% (P = 0.05), leading to an increased need for
      surgical intervention from 16.7% to 42.9% (P = 0.05). In contrast prior usage of
      anticoagulants, which could be antagonized, did not affect the clinical outcome
      of the bleeding. Mortality was 9.5% in the NSAID group, 0% in the coumarin group,
      and 4.2% in the no-medication group. CONCLUSION: Prior use of NSAIDs increases
      the risk of rebleeding in bleeding ulcer patients, and leads to a higher need for
      urgent surgery. In contrast, prior anticoagulant therapy does not raise the
      rebleeding risk.

PMID- 9031898
TI  - Short-term low-dose triple therapy with azithromycin, metronidazole and
      lansoprazole appears highly effective for the eradication of Helicobacter pylori.
AB  - BACKGROUND: Although the OCN (omeprazole, clarithromycin and nitroimidazoles)
      short-term low-dose regimens are regarded as 'the standard' in the treatment of
      Helicobacter pylori infection, azithromycin is a new-generation, acid-stable
      macrolide which may prove particularly useful for a new short-term low-dose
      triple therapy regimen. OBJECTIVE: To further improve OCN eradication treatments
      by reducing both the number of pills and the total cost. METHODS: A new short
      term low-dose triple therapy (LAM) using lansoprazole 30 mg once a day for 1
      week, azithromycin 500 mg once a day for 3 days, and metronidazole 250 mg twice a
      day for the same 3 days, was administrated to 60 patients presenting with H.
      pylori-positive gastritis with or without peptic ulcer, and compared with the
      classic 'Bazzoli regimen' (OCT: omeprazole, clarithromycin, tinidazole) in 60
      matched patients. H. pylori infection before and after therapy was evaluated by a
      rapid urease test, conventional histology and toluidine-stained semi-thin
      sections. Three biopsies from the corpus and three from the antrum were taken
      during endoscopical examination before and 7-8 weeks after discontinuation of the
      treatment. Patient compliance, drug tolerance and drug costs were also taken into
      consideration. RESULTS: H. pylori infection was eradicated 7-8 weeks after
      treatment in 56 of the 60 patients in the LAM group (93.3%), and in 52 of the 57
      patients in the OCT group who completed the treatment (91.2%), with no
      statistical difference. When gastric or duodenal ulceration was present, ulcer
      healing was observed in all cases. CONCLUSION: The new proposed short-term low
      dose triple therapy (LAM) appears to be as effective as the OCT for the
      eradication of H. pylori infection. The new treatment, however, seems to have
      advantages in terms of drug tolerance, patient compliance and therapy cost.

PMID- 9031899
TI  - Ongoing gastric acid inhibition is a confounding factor in Helicobacter pylori
      diagnosis.
AB  - BACKGROUND: Eradication of Helicobacter pylori by antibiotics in combination with
      gastric acid inhibition can result in overgrowth of non-H. pylori bacterial
      flora. This may confound the histological detection of H. pylori at eradication
      control if non-specific staining methods are used. OBJECTIVE AND METHODS: In 18
      patients treated with amoxycillin (2 weeks) and omeprazole (6 weeks),
      endoscopically obtained gastric juice was cultured and two biopsies of corpus,
      antrum and duodenum were taken before and after eradication therapy (with gastric
      acid inhibition still going on) for culture and for histology to assess the
      intragastric bacterial flora. By histology, modified Giemsa (MG) and an H. pylori
      specific immunohistochemical stain (IMM) were evaluated. RESULTS: Median pH of
      gastric juice was 1.5 (n = 18) before and 7 (n = 17) after eradication therapy,
      when patients were still on omeprazole. After therapy, culture showed a
      significant decrease (P < 0.05) in mean amount of H. pylori in corpus, antral and
      duodenal biopsies and a significant increase of non-H. pylori flora (P < 0.05) in
      gastric juice, corpus, antral and duodenal mucosa. With culture as a standard, 16
      and 4 biopsy specimens were scored falsely positive for H. pylori by MG and IMM,
      respectively, and H. pylori was not detected in 23 and 13 biopsy specimens when
      culture was H. pylori-positive. CONCLUSION: Because of the possible presence of
      non-H. pylori flora after eradication therapy, the use of IMM is recommended in
      this situation for the histological detection of H. pylori, especially in those
      patients with ongoing gastric acid inhibitory therapy.

PMID- 9031900
TI  - Haemodynamic changes after high-volume plasmapheresis in patients with chronic
      and acute liver failure.
AB  - OBJECTIVE: To evaluate the haemodynamic changes during treatment with high-volume
      plasmapheresis in patients with chronic liver failure compared to patients with
      acute liver failure. METHODS: Haemodynamic measurements were performed with a
      Swan-Ganz catheter and thermodilution technique. High-volume plasmapheresis (mean
      plasma exchange of 8.6 litres) was performed in 11 patients with chronic and 16
      patients with acute liver failure. RESULTS: In patients with chronic liver
      failure, systemic vascular resistance index was unaltered: 1193 +/- 494 dynscm
      5m2 before treatment versus 1180 +/- 399 dynscm-5m2 after. Mean arterial pressure
      increased from 69 +/- 11 mmHg to 78 +/- 13 mmHg (P < 0.05) and cardiac output
      increased from 8.1 +/- 2.4 l/min to 8.9 +/- 2.4 l/min (P < 0.05) during high
      volume plasmapheresis. In patients with acute liver failure, systemic vascular
      resistance index increased from 1154 +/- 628 dynscm-5m2 to 1614 +/- 738 dynscm
      5m2 (P < 0.001). In this group mean arterial pressure increased from 78 +/- 16
      mmHg to 95 +/- 10 mmHg (P < 0.001) and cardiac output decreased from 9.6 +/- 3.7
      l/min to 8.2 +/- 2.9 l/min (P < 0.01). CONCLUSION: The hyperkinetic circulation
      in chronic and acute patients was differently affected by high-volume
      plasmapheresis. We suggest that in chronic liver failure both portosystemic
      shunting and chronic peripheral vasodilation may contribute to the hyperkinetic
      syndrome, whereas in acute liver failure a humoral factor which can be removed by
      high-volume plasmapheresis is a main contributor.

PMID- 9031901
TI  - Epidemiology of liver cirrhosis morbidity and mortality in Iceland.
AB  - BACKGROUND: The mortality from liver cirrhosis in Iceland is the lowest in the
      Western world. OBJECTIVE: To study the epidemiology of liver cirrhosis mortality
      and morbidity in Iceland and to obtain a reliable separation between alcoholic
      cirrhosis (AC) and non-alcoholic cirrhosis (NAC) by using multiple data sources.
      METHODS: The study included the whole population of Iceland. Mortality was
      studied through death certificate data for the period 1951-90 and morbidity
      (clinical incidence) through hospital, autopsy and biopsy records for the period
      1971-90. RESULTS: The average mortality for AC in age group 20 years and older
      was 8.6 and for NAC 19.2 per 10(6)/year and the average clinical incidence was
      22.1 per 10(6)/year for AC and 25.9 per 10(6)/year for NAC. In the morbidity
      study 44% of cases were due to AC. In the mortality study 24% of cases were due
      to AC but the data suggested an underreporting of AC for males at a rate of 30%.
      There was a significant decrease in AC mortality with time but no change in NAC.
      Average alcohol consumption of inhabitants aged over 15 years increased from 2.1
      to 4.9 litres per year (130%) during the period 1951-90. CONCLUSION: The
      incidence of cirrhosis in Iceland is very low for both AC and NAC, accounting for
      only 0.2% of total deaths. The reasons are unknown. The low incidence of AC in
      Iceland is probably partly due to low alcohol consumption. The decreasing
      incidence of AC despite 130% increase in alcohol consumption is thought to be due
      to intensive treatment of alcoholism. A low prevalence of hepatitis B and C
      probably contributes to the low incidence of NAC.

PMID- 9031902
TI  - HCV-RNA levels play an important role independently of genotype in predicting
      response to interferon therapy.
AB  - OBJECTIVE: To evaluate the relationship between hepatitis C virus (HCV)-RNA
      levels and genotypes in order to establish their potentially predictive role in
      interferon (IFN) response. DESIGN: To detect HCV genotype at baseline and HCV
      viraemia levels before and during IFN treatment in three groups of patients with
      different IFN response. METHODS: Our study included 85 patients with biopsy
      proven chronic hepatitis C who underwent IFN therapy at standard schedule (3 MU
      thrice weekly for 6 months). On the basis of IFN response they were subdivided
      into three groups as follows: non responders (NR: 27 cases) when alanine
      aminotransferase (ALT) values (normal value: 0-40 IU) at the end of treatment
      were abnormal (101.7 +/- 10.4); responders relapsing (RR: 29 cases) when normal
      ALT values at the end of therapy (28.14 +/- 1.7) increased during follow-up;
      sustained (long-term) responders (LTR: 29 cases) when ALT values remained normal
      for at least 12 months of follow-up (ALT values at the end of therapy: 21.8 +/-
      1.4). ALT activity was monitored monthly during therapy and each month during 12
      months of follow-up. HCV genotype was evaluated before starting treatment whereas
      HCV-RNA viraemia was checked at baseline and at the 1st and 6th months of
      therapy. RESULTS: The baseline viral load was higher in the NR group than in the
      RR and LTR groups independently of genotype; HCV-RNA levels progressively
      decreased during therapy independently of response but the levels remained
      significantly higher in the NR group. Genotype 1b was prevalent in the NR group.
      However, levels of viraemia in genotype 1b LTR patients are significantly lower
      than in genotype 1b NR patients. CONCLUSION: These results suggest that among
      viral-related parameters viraemia alone seems to play an important role in
      predicting response to IFN independently of genotype.

PMID- 9031903
TI  - Spontaneous ascitic infection in different cirrhotic groups: prevalence, risk
      factors and the efficacy of cefotaxime therapy.
AB  - OBJECTIVE: To investigate the prevalence of spontaneous ascitic infection (SAI)
      in different cirrhotic groups, the risk factors for development of SAI, and the
      efficacy of cefotaxime therapy. DESIGN: A prospective study. SETTING: In-patient
      clinic of a university hospital. PATIENTS: Eighty cirrhotic patients with ascites
      were assigned to four groups: hepatitis B or D virus-related 34, alcoholic 18,
      hepatitis C virus-related 14, miscellaneous 14. INTERVENTIONS: Paracentesis was
      performed on 80 patients during 92 consecutive hospitalizations. Ascitic fluid
      was cultured by the method of bedside inoculation of blood culture bottles with
      ascites. The patients with SAI were treated with cefotaxime (2 g, three times
      daily, intravenously) for 5 days. MAIN OUTCOME MEASURES: Frequency of SAI in
      cirrhotic groups; clinical, bacteriological and biochemical findings of SAI; rate
      of recovery-from infection. RESULTS: Twenty SAI episodes (22%) were found in 16
      patients; 8 episodes were spontaneous bacterial peritonitis, 2 bacterascites, and
      10 culture-negative neutrocytic ascites. SAI occurred more frequently in patients
      with hepatitis B or D virus-related liver cirrhosis (32%) than in the alcoholic
      (6%, P < 0.05), hepatitis C virus-related (14%) or miscellaneous (14%) cirrhotic
      groups in multivariate analysis, independent predictive factors associated with
      the development of SAI are chronic hepatitis B virus infection, ascitic fluid
      total protein and serum bilirubin. Escherichia coli was obtained in 5 of 10
      positive ascitic fluid cultures. Cure of the infection was achieved in 95% of
      episodes. Hospitalization mortality rate in infected patients was 20%.
      CONCLUSION: Spontaneous ascitic infection occurs in approximately 20% of
      cirrhotic patients hospitalized with ascites. The patients with low ascitic
      protein concentration, high serum bilirubin level or hepatitis B virus cirrhosis
      are more predisposed to SAI. Cefotaxime may be an effective first-choice
      antibiotic for ascitic fluid infection.

PMID- 9031904
TI  - Jaundice at onset signifies a good prognosis in anti-D-associated HCV infection.
AB  - INTRODUCTION: Acute hepatitis presenting with jaundice occurs in less than a
      quarter of patients infected with the hepatitis C virus (HCV). These patients may
      be associated with a more benign clinical course than those who are asymptomatic.
      OBJECTIVE: To compare and contrast the polymerase chain reaction (PCR) and
      recombinant immunoblot assay (RIBA) status, serum alanine aminotransferase (ALT)
      levels and histological scores in age, disease duration and viral load matched
      HCV anti-D recipients with and without a history of jaundice. METHODS: HCV status
      was confirmed by detecting HCV-RNA by PCR and antibodies to HCV using enzyme
      linked immunosorbent assay (ELISA) and RIBA-3. Serum ALT levels were measured in
      all patients and a liver biopsy was performed in 26/34 patients. All patients
      were genotyped. RESULTS: Fourteen out of 17 jaundiced patients were PCR negative
      and only 4/17 had RIBA scores greater than 9, whereas all non-jaundiced patients
      were PCR positive and all 17 had RIBA scores greater than 9. Thirteen out of 17
      jaundiced patients had normal ALT values, 3/17 mildly elevated (41-100) and 1/17
      greater than 100; 6/17 non-jaundiced patients had normal ALT levels, 9/17 mildly
      elevated (41-100) and 2/17 greater than 100; 7/9 jaundiced patients had mild
      histological scores, 0/9 moderate and 2/9 severe; 5/17 non-jaundiced patients had
      mild, 9/17 moderate and 3/17 severe histological scores. All 34 patients were of
      genotype 1b. CONCLUSION: Patients with jaundice had lower antibody scores,
      increased PCR negativity, normal serum ALT levels and low/normal histological
      scores. Jaundice at onset was an indicator of good prognosis.

PMID- 9031905
TI  - Absorption of hydrolysed bovine serum albumin from the human jejunum over a 6
      hour period.
AB  - OBJECTIVE: Quantitative assessment of intestinal absorption of total and single
      amino acids in a hydrolysed bovine serum albumin solution over a 6-h period.
      DESIGN: Ten healthy volunteers underwent segmental jejunal perfusion using a
      multi-lumen tube assembly with a proximal occluding balloon. Prehydrolysed bovine
      serum albumin served as protein source. In one set of experiments we used a
      washout phase before the equilibration period to eliminate any contents present
      in the test segment. In another set we started directly with the equilibration
      period. Absorption rates of total and single amino acids were measured over a
      period of 6 h. RESULTS: Absorption rates remained constant throughout this period
      and there was no significant difference in absorption rates whether a washout
      phase was used or not. Absorption rates of total amino acids ranged from 6.4 +/-
      1.9 (mean +/- SEM) to 10.7 +/- 0.7 g/h and 30 cm, when a washout phase was used.
      Percentage absorption of the perfusion load per hour was 24 +/- 7% to 40 +/- 2%
      with a washout phase. Although a highly concentrated perfusion load was used
      there was a correlation (r = 0.66, P < 0.05) between absolute concentration in
      the perfusion solution and the amount of individual amino acid absorbed.
      Individual amino acids showed a wide range of percentage absorption. Percentage
      absorption of 50% or more of the perfusion load was seen for alanine,
      phenylalanine, arginine, leucine, methionine and tyrosine. The highest absorption
      rate was seen for methionine with 86%, the lowest for cysteine with 3%.
      CONCLUSION: When hydrolysed bovine serum albumin is used, amino acid absorption
      is constant over a period of 6 h in the human jejunum. A washout phase has no
      influence on total and single amino acid absorption.

PMID- 9031906
TI  - Primary hepatic lymphoma in a man with chronic hepatitis C.
AB  - We report the case of a middle-aged man who presented de novo with abdominal pain
      and hepatomegaly and was found to have positive serology for hepatitis C and
      subsequently a primary hepatic lymphoma. An increased incidence of primary
      hepatocellular cancer is well characterized in both cirrhotic and non-cirrhotic
      cases of chronic hepatitis C. The relationship between chronic hepatitis C and
      primary hepatic lymphoma remains obscure. It has been established that hepatitis
      C can sustain the clonal B-cell expansion that occurs in associated
      cryoglobulinaemia, and hepatitis C RNA has been detected within extrahepatic
      lymphoma tissue. Viral aetiologies for lymphoma are well characterized, such as
      Epstein-Barr virus (EBV) and human T-cell leukaemia virus (HTLV) I and II.
      Existing models of chronic infection causing lymphoma within the gastrointestinal
      tract include that of Helicobacter pylori and mucosa-associated lymphoid tumour
      of the stomach. Given the relatively low frequency of occurrence it may be
      prudent to perform a retrospective analysis on past cases of primary hepatic
      lymphoma in order to determine whether or not hepatitis C was present.

PMID- 9031907
TI  - Misoprostol-associated platelet aggregation dysfunction and increased
      gastrointestinal blood loss.
AB  - We report a case where an acquired deficit in platelet aggregation was associated
      with the use of misoprostol and contributed to increased gastrointestinal blood
      loss. A 70-year-old man presented with chronic gastrointestinal blood loss
      secondary to widespread telangiectases. Investigations showed prolonged bleeding
      time and severely impaired platelet aggregation in vitro. Withdrawal of
      misoprostol resulted in resolution of the prolonged bleeding time and improvement
      in the platelet dysfunction. We conclude that misoprostol can lead to impaired
      platelet function and may exacerbate blood loss.

PMID- 9031908
TI  - Nurse endoscopists and percutaneous endoscopic gastrostomy (PEG) insertion.

PMID- 9031909
TI  - Why do women menstruate? Historical and evolutionary review.
AB  - Theories regarding the significance of menstruation from the time of Aristotle to
      the present are reviewed, followed by a brief description of the evolutionary
      changes in the uterus. A specific duct for the transport of ova first appears in
      jawed fishes. Its important role in the evolution of internal fertilisation and
      the protection and nourishment of the embryo is followed through the vertebrate
      orders, amphibia, reptiles and mammals. The problems associated with the presence
      of a gamete or zygote of different genetic make up inside the maternal tract is
      stressed, and the mechanisms to overcome or modify the maternal inflammation
      reaction discussed. In egg laying reptiles and birds, the secretion of coverings
      around the embryo presumably shields the foreignness of the tissue, while in
      viviparous animals, the secretion of progesterone plays a major role in
      controlling the inflammatory reaction. In some mammals, for example the mouse,
      the invasiveness of the trophoblast is such that the blastocyst penetrates inside
      the wall of the endometrium. The stroma responds under the influence of
      progesterone, to undergo an implantation/decidual reaction which bears
      considerable resemblance to an inflammatory/granulation tissue reaction. A
      similar reaction occurs in women during the luteal phase in anticipation of a
      very invasive blastocyst. When there is no fertilisation the progesterone drops
      and the differentiated stromal tissue is shed with bleeding; menstruation.

PMID- 9031910
TI  - Oestrogen and progestogen receptor content in human endometrium.

PMID- 9031911
TI  - Androgen receptor content in human endometrium.
AB  - Human endometrium changes morphologically and biochemically during the various
      phases of the menstrual cycle, influenced by not only estrogens and progesterone,
      but probably also by androgens. The purpose of this study was to investigate the
      androgen receptor (AR) content in human endometrium and myometrium and its
      significance. AR immunocytochemistry was performed on 30 paraffin-embedded
      uterine sections of pre-menopausal women who were scheduled for hysterectomy
      because of benign gynaecologic abnormalities. AR receptor content was seen in all
      cell types of the human endometrium and myometrium and was cyclic dependent. AR
      immunostaining of stromal and smooth muscle cells was more profound than AR
      staining of glandular cells. There was more AR expression in the proliferative
      phases than in the secretory phases: in the late secretory phase there was no
      immunostaining in any of the cell types. AR expression is primarily under
      androgenic control. Inside the cell testosterone may be 5 alpha-reduced to
      dihydrotestosterone (DHT). Due to local competition between testosterone and the
      excess of progesterone in the secretory phase for the same iso-enzyme 5 alpha
      reductase, the level of DHT will be diminished in the late secretory phase. If AR
      synthesis in endometrium would be DHT dependent, the virtual disappearance of DHT
      would explain the lack of AR expression in the late secretory phase. Whether the
      cyclic pattern of AR expression is merely an epiphenomenon to progesterone
      production, or whether androgens play a causal role in the cyclic modulation of
      endometrium is subject to further research.

PMID- 9031913
TI  - Hemostasis in menstrual endometrium.

PMID- 9031912
TI  - Prostaglandins and menstruation.

PMID- 9031914
TI  - A simple visual assessment technique to discriminate between menorrhagia and
      normal menstrual blood loss.

PMID- 9031915
TI  - Subendometrial contractions in the nonpregnant uterus: an ultrasound study.
AB  - Endometrial wavelike activity was studied by ultrasound, throughout 19 ovulatory
      cycles in 16 healthy female volunteers. Analysis was focused on the presence of
      endometrial activity and the wave types. Five activity patterns were
      distinguished, which varied throughout the cycle. Endometrial activity was most
      striking during the periovulatory phase.

PMID- 9031916
TI  - From steroid signals to local regulatory factors involved in endometrial
      bleeding.

PMID- 9031917
TI  - Intravenous nitroglycerin for intrapartum internal podalic version of the second
      non-vertex twin.
AB  - OBJECTIVE: Authors report their experience of intravenous nitroglycerin as
      uterine relaxing agent for managing successfully internal podalic version of the
      second twin. METHODS: From a retrospective study including nine observations of
      internal podalic version of the second non vertex twin performed with
      administration of intravenous nitroglycerin, between August 1994 and February
      1996, authors compare their results with those reported elsewhere. RESULTS: Two
      failures of internal podalic version with nitroglycerin have been observed. But
      one failure is not considered to be due to the NTG: it was a patient, who had a
      panic attack necessitating a general anesthesia for sedative purpose. The
      internal podalic version succeeded. The true failure of NTG needed an emergency
      cesarean due to acute fetal distress and a non relaxing uterus. One internal
      podalic version was complicated by hemorrhage. The intravenous NTG used to induce
      uterine atonia associated with epidural-analgesia to relief pain avoiding general
      anesthesia makes internal podalic version easier. CONCLUSION: Our results
      confirmed those already reported. That intravenous nitroglycerin (NTG) injection
      induces a transient and prompt uterine relaxation required for internal podalic
      version without affecting maternal and fetal prognosis.

PMID- 9031919
TI  - Polyhydramnios is an independent risk factor for perinatal mortality and
      intrapartum morbidity in preterm delivery.
AB  - OBJECTIVE: To investigate the clinical significance of polyhydramnios as a
      predictor of perinatal death and intrapartum morbidity in patients with preterm
      delivery. STUDY DESIGN: The study population consisted of 4211 patients with
      singleton gestation, intact membranes and preterm delivery (< 37 weeks). Two
      groups were identified and compared according to the sonographic assessment of
      the amniotic fluid volume: increased and normal amniotic fluid. Analyses were
      conducted for the entire cohort as well as for the cohort excluding from each
      group all cases with congenital malformations. Logistic regression was used to
      assess the unique contribution of polyhydramnios to mortality and morbidity in
      the presence of other known risk factors. RESULTS: The prevalence of
      polyhydramnios among women who delivered preterm was 5% (210/4211) including and
      3.7% (142/3818) excluding the cases of congenital malformations, respectively.
      Polyhydramnios was associated with a higher rate of diabetes, large for
      gestational age neonates, fetal malpresentation at delivery, previous perinatal
      death and with a lower Apgar score at 1 and 5 min. Polyhydramnios was an
      independent predictor of perinatal mortality and intrapartum morbidity. When
      adjusted for well recognized risk factors for perinatal mortality and intrapartum
      morbidity (e.g. diabetes, severe pregnancy induced hypertension, multiparity,
      congenital malformation, previous perinatal death, low gestational age at
      delivery), the presence of polyhydramnios significantly increased the rate of
      perinatal mortality (odds ratio (OR) 5.8; 95% confidence interval (CI) 3.68-9.11)
      and of intrapartum morbidity (OR 2.8; 95% CI 1.94-4.03). CONCLUSION: In the
      setting of preterm delivery, polyhydramnios is an independent risk factor for
      perinatal mortality and intrapartum complications even in the absence of
      congenital malformation and other conditions traditionally associated with
      increased perinatal mortality and morbidity.

PMID- 9031920
TI  - Micro-albuminuria analysis and pregnancy. An approach to detect placentary
      insufficiency?
AB  - OBJECTIVE: To assess the value of micro-albuminuria analysis (MA) in predicting
      clinical complications of placentary insufficiency in women with no known risk
      factor. STUDY DESIGN: A blind prospective investigation 20-24 weeks into
      pregnancy in a nulliparous population with no known risk factor. A reactive strip
      with a positive threshold value of 10 mg/l is used to detect MA. Judgment
      criteria concerning the progress of pregnancy are based on blood pressure during
      the 8th and 9th month of pregnancy and on the 2nd day after delivery, on
      albuminuria analysis in the 8th and 9th month of pregnancy and by the existence
      of fetal hypotrophia at birth. RESULTS: Some 218 patients participated in the
      investigation. MA was positive in 62 cases (28.4%). Of the 197 births which
      occurred 54 (27.4%) cases of positive MA, 34 (17.2%) cases presented positive
      judgment criteria indicating placentary insufficiency. The 21 others pregnancies
      are in course. MA sensitivity was thus 79.4% and specificity 83.4%. Negative
      predictive value (NPV) was 95.1% and positive predictive value (PPV) 50%.
      CONCLUSION: Our test is a reliable, simple and easily reproducible indicator of
      micro-albuminuria. In comparison with other tests it gives a good detection rate
      of a risk group for complication of placentary insufficiency. NPV is excellent,
      virtually excluding the occurrence of excessive blood pressure or intra-uterine
      growth retardation. PPV is less good.

PMID- 9031918
TI  - Fibronectin and antithrombin as markers of pre-eclampsia in pregnancy.
AB  - INTRODUCTION: The differential diagnosis between pre-eclampsia and chronic
      hypertension is not easy, but is essential to proper management of a pregnancy.
      Patients presenting pre-pregnancy hypertension can be treated conservatively, if
      not a superimposed pre-eclampsia occurs, controlling pressure pharmacologically
      and completing the pregnancy with a natural delivery. In pre-eclampsia,
      hypertension is merely the visible sign of a process of endothelial damage and
      coagulation cascade activation which is often destined to emerge clinically on a
      dramatic scale. MATERIALS AND METHODS: The study involved 18 women with
      physiological pregnancies, 19 with pre-eclampsia and 13 with chronic hypertension
      since superimposed pre-eclampsia. The following laboratory tests were performed:
      PT, PTT, AT-III, proteins C and S, platelet count, D-dimer, fibrinogen and plasma
      fibronectin. The three groups were compared using the Kruskall Wallis test, the
      median test and, for multiple comparisons, the Mann-Whitney test. A 'P' value of
      < 0.01 was considered as statistically significant. RESULTS: The values for
      plasma fibronectin were higher in the pre-eclampsia group (410 mg/l (253-727))
      than in controls (262 mg/l (183-385)) (P < 0.01) and values for AT-III were lower
      in the pre-eclampsia group (73% (40-100)) than in controls (93% (80-126) (P <
      0.01) (Table 2). The groups with chronic hypertension revealed no such
      significant differences, however, in relation to the control group (fibronectin =
      296 mg/l (198-530), AT-III = 86% (75-103)). CONCLUSIONS: Measuring antithrombin
      and fibronectin to monitor any onset of pre-eclampsia can help the obstetrician
      to avoid important diagnostic and therapeutic errors.

PMID- 9031921
TI  - Risk factors for preterm birth in an upper middle class Chinese population.
AB  - OBJECTIVE: To examine the risk factors associated with preterm birth in an upper
      middle class Chinese population. STUDY DESIGN: From March 1994 to February 1995,
      a total of 301 cases (gestational age between 20 and 37 weeks) and 656 controls
      (gestational age at or greater than 37 weeks) were recruited at Mackay Memorial
      Hospital, Taipei, Taiwan. Using a case-control study design, logistic regression
      was used to examine the relative significance of various risk factors associated
      with preterm birth. RESULTS: Age and educational level were identified as
      significant risk factors for preterm birth. Multiple pregnancies, fetal
      congenital anomalies, placenta previa or abruptio placentae, and preeclampsia
      were found to be strongly associated with preterm birth (crude odds ratios
      between 6.37 and 25.89); vaginal bleeding during or after the first trimester,
      prior history of preterm delivery, and two or more previous first trimester
      abortions were associated with preterm birth to a lesser extent (crude odds
      ratios between 1.67 and 2.9). The magnitude of the increased risk associated with
      these variables in preterm birth did not show change to any great extent after
      age and educational level were adjusted for. Further stratification of these
      cases into groups with and without premature rupture of the membranes (PROM),
      showed that a multiple pregnancy was still the leading risk factor of preterm
      birth in both groups. Carrying an abnormal fetus was the next important risk
      factor for preterm birth in cases with PROM, but was less important in the group
      without PROM. However, placenta previa or abruptio placentae and preeclampsia
      were the next most important factors in the group without PROM. CONCLUSIONS:
      Unfavorable current obstetric conditions and a history of more than two prior
      abortions and preterm delivery were positively associated with preterm birth.

PMID- 9031922
TI  - Fetal distress due to placental insufficiency at 26 through 31 weeks: a
      comparison between an active and a more conservative management.
AB  - OBJECTIVE: To compare perinatal mortality and short-term morbidity in extremely
      preterm infants with fetal distress due to placental insufficiency in two centers
      with different management attitude. DESIGN: Retrospective cohort study in two
      university hospitals of all infants with fetal growth retardation due to
      placental insufficiency resulting in signs of fetal distress at 26 through 31
      weeks gestational age, during the years 1984 through 1989. Center A followed a
      conservative management: in some cases the risk of major handicaps or mortality
      was estimated so high, based on antenatally estimated fetal weight and
      gestational age, that the decision was taken to abstain from treatment. In all
      other cases cesarean section took place, but only if fetal distress was obvious.
      Center B used a more active management: cesarean section was performed in all
      cases, sometimes with only minor changes in fetal heart rate variability.
      RESULTS: Overall survival differed significantly: 55% (center A) versus 72%
      (center B), largely due to antenatal mortality in center A. Discharge survival
      rate of liveborn infants was 81% in center A and 72% in center B. More than half
      of the postnatal mortality was attributed to respiratory causes in both centres.
      An active management showed a tendency to a higher incidence of short-term
      morbidity. CONCLUSION: Selection by antenatal prediction of postnatal mortality
      using estimated fetal weight fails. Even in the group with the lowest birthweight
      postnatal mortality did not surpass 50%. Early intervention may be associated
      with higher short-term morbidity. Long-term follow-up of these children is needed
      to discriminate between both policies with regard to further development of
      surviving infants.

PMID- 9031924
TI  - Hemodynamic assessment in pelvic inflammatory disease by transvaginal color
      Doppler ultrasonography.
AB  - One of the major signs of inflammation is a change in vascular flow and caliber.
      It is possible to detect these changes with the help of transvaginal color
      Doppler velocitometry. The purpose of this study was to evaluate the changes in
      pelvic circulation in cases with pelvic infection and to correlate these findings
      with other infectious parameters. The study group consisted of 20 cases who had
      the diagnosis of pelvic inflammatory disease (PID). Resistance index (RI) and
      pulsatility index (PI) were measured with transvaginal color Doppler
      ultrasonography in the uterine and ovarian arteries as well as at the tubouterine
      junction three times in a one-month period. At the same time the body
      temperature, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and
      leukocyte counts were recorded. Infectious parameters declined to normal values,
      following a pattern parallel to clinical improvement from the first until day 30.
      Infectious parameters revealed significant differences between days 1-7, 1-30 and
      7-30. On the other hand, low resistance in all three measurement points exhibited
      a rapid increase on the day 7 day and plateaued until the day 30 day. Color
      Doppler velocitometry measurements revealed significant differences between days
      1-7 and 1-30 but not between days 7-30. These findings demonstrate that as the
      infection subsides, the changes in vascular flow return to normal before
      infectious parameters do. In conclusion, it is possible to detect decreased
      vascular resistance in acute infection with the help of transvaginal color
      Doppler ultrasonography. Furthermore, color Doppler ultrasonography can
      accurately detect regression of the infectious process before body temperature
      and acute phase reactants do.

PMID- 9031923
TI  - Malignant tumors arising in endometriosis: clinical-pathological study and flow
      cytometry analysis.
AB  - BACKGROUND: Malignant transformation to endometriosis is a well documented
      phenomenon that occurs most commonly in the ovaries with cancer arising in extra
      ovarian endometriosis being a rare event. METHODS: A retrospective clinical
      pathological evaluation of eleven cases with malignant tumors arising in
      endometriosis was performed to evaluate the prognostic impact of various factors.
      Nuclear DNA content (ploidy) was assessed through flow cytometric study. RESULTS:
      Ovarian origin was identified in eight cases and three were associated with extra
      ovarian endometriosis. Histologic type was endometrioid carcinoma in ten
      patients. The eleventh case had high grade endometrial stromal sarcoma. All
      tumors were diploid with no relation to stage, grade, or clinical outcome. The S
      phase fraction (SPF) was analyzed in nine patients and no correlation could be
      demonstrated with any histologic parameters or clinical outcome. CONCLUSIONS: The
      DNA content seems to have no association with the classical prognostic parameters
      in these cases.

PMID- 9031925
TI  - The combination of p53 and age predict cancer specific death in advanced stage
      (FIGO Ic-IV) of endometrial carcinoma of endometrioid type. An
      immunohistochemical examination of growth fraction: Ki-67, MIB-1 and PC10;
      suppressor oncogene protein: p53; oncogene protein: p185 and age, hormone
      treatment, stage, and histologic grade.
AB  - OBJECTIVE: Early surgical stage (FIGO Ia + b) is an excellent predictor of
      survival in endometrial carcinoma of endometrioid type (EC), in contrast to
      advanced stage which only predict cancer specific death (CSD) in approximately 20
      30% of the patients. The value of growth fraction, p53 and p185 as predictor of
      CSD in EC was studied. STUDY DESIGN: One hundred and eleven patients (45% hormone
      users) with EC were entered prospectively and consecutively into an
      immunohistochemical study of growth fraction (Ki-67, MIB-1 and PC10), suppressor
      oncogene protein (p53) and oncogene protein (p185). RESULTS: All markers except
      p185 intercorrelated significantly, although weakly, however, marked differences
      were found in median values of the markers of growth fraction (GF). It was shown
      that immunohistochemical demonstration of p53 and p185 proteins and stage
      correlates independently with CSD in EC. CONCLUSION: The study indicates that the
      markers of GF do not give exact information about the proliferative compartment
      of the EC, and it is shown that p53 correlate to CSD, while stage indicate crude
      death.

PMID- 9031926
TI  - A cost comparison of hysterectomy and hysteroscopic surgery for the treatment of
      menorrhagia.
AB  - OBJECTIVES: To estimate and compare the costs of treating women with menorrhagia
      by hysterectomy or hysteroscopic surgery, in the form of transcervical resection
      of the endometrium (TCRE) or endometrial laser ablation (ELA). STUDY DESIGN:
      Randomised controlled trial set in the gynaecological department of a large
      British teaching hospital. Under usual circumstances, 204 women who would have
      undergone hysterectomy for menorrhagia were randomly allocated to either
      hysterectomy (n = 99) or hysteroscopic surgery in the form of TCRE (n = 52) or
      ELA (n = 53). National Health Service (NHS) costs and costs to patients per
      patient occurring up to 1 year following surgery were estimated. Theatre times
      and length of hospital stay were recorded during the trial. Costs were obtained
      from the health board finance department and relevant suppliers of technical
      equipment. One year after treatment patients completed questionnaires on personal
      costs incurred. RESULTS: The NHS costs of treating women with hysteroscopic
      surgery were 24% (TCRE) or 20% (ELA) less than treating women by hysterectomy
      (1001 pounds/1046 pounds vs. 1315 pounds). On average, women undergoing
      hysteroscopic surgery incurred 71% less costs to themselves than those who
      underwent hysterectomy (21 pounds vs. 73.40 pounds). CONCLUSIONS: Hysteroscopic
      endometrial ablation incurs less costs than hysterectomy both to the National
      Health Service and to women alike, up to 1 year after surgery.

PMID- 9031927
TI  - Primary carcinoma of the fallopian tube: report on two cases.
AB  - Two cases of carcinoma of the Fallopian tube were treated by total abdominal
      hysterectomy, bilateral salpingo-oophorectomy and omentectomy followed by
      chemotherapy consisting of several courses of a cisplatin, epirubicin and
      cyclophosphamide combination. One patient received three additional courses of
      combined cisplatin-taxol. At 60 months from onset of therapy one patient (Stage
      IIa-Grade 1 tumor) is alive and well, while the other (Stage III-Grade 3 tumor)
      died of disease 26 months from initial treatment. Second-look laparotomy proved
      useful in assessing response to chemotherapy. CA-125 blood levels helped
      monitoring tumor activity. Anamnestic data relevant to tuberculous salpingitis on
      one case, and bilateral salpingoplasty for tubal occlusion, in the other case,
      may stand for some remarks.

PMID- 9031928
TI  - Anticardiolipin antibodies in pregnancy induced hypertension.
AB  - It was suggested that anticardiolipin antibodies (ACA) were found positive in
      some obstetrical problems such as recurrent foetal losses, intrauterine growth
      retardation, etc. The aim of this study was to determine ACA levels in pregnancy
      induced hypertension (PIH) cases. ACA IgG and IgM levels were measured by the
      ELISA method in 65 PIH cases and 23 control pregnancies. We could not find any
      difference between the PIH and the control groups. There was not any
      statistically significant difference between the subtypes of PIH. According to
      these results, we say that ACA IgG and IgM levels have no diagnostic and
      prognostic value in PIH.

PMID- 9031929
TI  - Synthesis of glycosaminoglycans by human cervical fibroblasts in culture: effects
      of prostaglandin E2 and cyclic AMP.
AB  - OBJECTIVE: To study the mechanism of action of prostaglandin E2 (PGE2) and its
      analogue sulprostone leading to production of glycosaminoglycans (GAGs) in the
      human uterine cervix. STUDY DESIGN: We analysed the effects of PGE2 and its
      analogue sulprostone upon production of adenosine 3',5'-monophosphate (cAMP), in
      human cultured fibroblasts. We also studied the effects of PGE2, sulprostone and
      a cAMP analogue (8-Bromo-cAMP), on the incorporation of [3H]glucosamine into GAGs
      in human cervical fibroblasts in culture. RESULTS: Following treatment with PGE2
      (10(-4)-10(-6) M), we observed a significant increase in the production of cAMP
      from 96.3 +/- 8.4 pmol/10(6) cells without phosphodiesterase inhibitor 3-isobutyl
      methylxanthine (IBMX) to 325 +/- 63 pmol/10(6) cells with 10(-4) M IBMX (Spearman
      correlation test; P < 0.05). Under the same conditions, the effects of
      sulprostone (10(-6) M) were limited (from 8.1 +/- 1.5 to 51.3 +/- 14.1 pmol/10(6)
      cells without and with IBMX, respectively; not significant). Both PGE2 and 8
      bromo-cAMP (from 10(-12) to 10(-4) M) increased [3H]glucosamine uptake into GAGs
      (Spearman correlation test; P < 0.05). Sulprostone (10(-12)-10(-4) M) was unable
      to reproduce such an effect even after a 24 or 48 h treatment. CONCLUSION: Since
      firstly, PGE2 acts through EP1, EP2 and EP3 specific receptors, whereas the
      action of sulprostone is only mediated by EP1 and EP3, and secondly EP2 receptor
      is coupled with cAMP production, we conclude that cAMP is involved in mediating
      the action of PGE2 upon GAG synthesis by human cultured cervical fibroblasts.

PMID- 9031952
TI  - Determinants of contraceptive use: from birth control to fertility awareness.

PMID- 9031954
TI  - Predictive value of Doppler umbilical artery velocimetry in a low risk population
      with normal fetal biometry. A prospective study of 2016 women.
AB  - OBJECTIVE: To assess the predictive value of Doppler umbilical artery velocimetry
      in a low-risk population with normal fetal biometry. STUDY DESIGN: Multicenter
      prospective study in 17 hospitals with prenatal clinics in France. Two thousand
      sixteen women who, before 28 weeks gestation were defined as at low risk after
      routine consultation and after ultrasound. Doppler umbilical artery velocimetry
      was performed between 28 and 34 weeks gestation. Confounding factors were used to
      perform multivariate regression. RESULTS: 1903 cases were analysed and 192
      (10.1%) had an abnormal Doppler Resistance Index (RI). The abnormal Doppler group
      contained a significantly higher frequency of severe and moderate small for
      gestational age infants (SGA), both severe and moderate with a sensitivity of
      25.5 and 18.8% respectively. There was no difference in hypertensive disorders or
      criteria of fetal distress. Mean birth weight was very significantly lower in the
      abnormal group (162 g). Birth weight was very significantly linked to RI after
      taking into account confounding variables in the multiple linear regression model
      (continuous relationship). After multiple logistic regression, the odds ratio
      associated with an abnormal Doppler result, adjusted for all the confounding
      factors, was 2.3 (95% CI 1.5-3.7) for moderate SGA and 3.5 (95% CI of 1.8-7.1)
      for severe SGA. CONCLUSION: Low umbilical Doppler RI is predictive with moderate
      or severe SGA in a low-risk population with normal fetal biometry, even when the
      information generally available in clinical practice and ultrasound parameters
      are taken into account. There is a continuous relationship between RI and
      birthweight. This predictive value cannot, however, lead to an improvement in
      neonatal health unless effective measures to prevent SGA exist and umbilical
      Doppler should not be used in low-risk population on a routine basis.

PMID- 9031953
TI  - Etiology, prognosis and management of nuchal cystic hygroma: 25 new cases and
      literature review.
AB  - OBJECTIVE: To develop an algorithm for the prenatal management of patients when a
      cystic hygroma is diagnosed by ultrasonography. METHODS: We report a personal
      series of 25 cases diagnosed between 10 and 23 weeks gestation and a review of
      the literature comprising a total of 999 cases. We focused on the etiologies and
      the value of various prognostic factors in the management of cystic hygromas.
      These include karyotype, alpha-fetoprotein levels, sonographic findings in the
      fetus and within the hygroma itself, and natural history. RESULTS: According to
      the literature, fetal chromosomal abnormalities were associated with cystic
      hygromas in 62% of the cases. Turner's syndrome remains the most common (33%) but
      Down's syndrome, Trisomy 18 and Trisomy 13 are not rare (15, 7 and 2%). Others
      have Mendelian abnormalities. The prognosis remains gloomy. The literature
      reports that only 9% of cases result in healthy children with normal karyotypes.
      The remaining 91% are either terminated (89%) or liveborn (2%), but with
      chromosome abnormalities or various malformations. CONCLUSION: The prognostic
      factors associated with a poor outcome are an abnormal karyotype and associated
      structural malformations. Resolution of the hygroma by 20 weeks gestation
      suggests a good prognosis, but is not definitive. All other factors evaluated do
      not appear to be of prognostic value at this time. Careful analysis of these
      prognostic factors is very important to identify the small percentage of normal
      children and to advise parents effectively for a future pregnancy.

PMID- 9031955
TI  - Fetomaternal haemorrhage discovered after trauma and treated by fetal
      intravascular transfusion.
AB  - Fetomaternal haemorrhage can occur spontaneously, or after abdominal trauma. We
      describe a case of fetomaternal haemorrhage diagnosed at 27 weeks gestation after
      blunt trauma. The Kleihauer-Betke smear on admission and during the first week
      was positive, ranging between 3% and 5%. Cordocentesis revealed a fetal
      haemoglobin of 8.8 gm/dl. An intravascular fetal transfusion was performed. The
      weeks until delivery and the neonatal period were unremarkable. Fetal anaemia can
      be a serious complication of fetomaternal haemorrhage, however, intravascular
      fetal transfusion is an effective treatment when this occurs. The Kleihauer-Betke
      test should be performed in every patient with a history of abdominal trauma
      during pregnancy.

PMID- 9031956
TI  - Glutathione status of placentae from differently polluted regions of Ukraine.
AB  - A study of the glutathione status as a prerequisite of the detoxifying activity
      of the fetoplacental barrier was undertaken in different regions of the Ukraine
      that have been judged either 'clean', chemically polluted or radioactively
      contaminated with different summary effective equivalent annual expositional
      doses (SEEAED). In the samples from clean regions, cytosolic glutathione
      transferase (GST), glutathione reductase (GSSG-R) activities and contents of
      total SH-groups were higher than in contaminated areas and corresponded to 50.4
      +/- 9.0. 13.6 +/- 1.8 mU/mg cytosolic protein and 30.2 +/- 5.7 mumol/g tissue,
      respectively. In heavily radioactively exposed women, e.g. 'liquidators' (SEEAED
      in 1986: > 5 mSv), low GST activity, 17.0 +/- 3.0 mU/mg cytosolic protein and
      high malonic dialdehyde concentration, 128.8 +/- 13 nmol/g tissue were found; the
      latter serves as a measure of lipid peroxidation. In the placental specimens from
      heavily exposed women, the distribution of GST pi-specific antigen along the
      villi was irregular and differed from specimens of unexposed women. Malonic
      dialdehyde concentrations in all other groups of women were in the range 37.1
      69.2 nmol/g tissue. In less exposed women, e.g. Kiev citizens and those from some
      rural areas (SEEAED in 1986: 4.9 and < 1 mSv, respectively), GST activity, 19.1
      +/- 2.1 and 33.7 +/- 5.0 mU/mg cytosolic protein, increased concomitantly with
      the total content of SH-groups, 7.4 +/- 1.0 and 15.3 +/- 1.6 mumol/g tissue, and
      with the decreasing values of the first year SEEAED. GST activity, 49.6 +/- 8.8
      mU/mg cytosolic protein, and total SH-group content, 19.8 +/- 0.5 mumol/g tissue,
      were even higher in the women evacuated on the second day after the catastrophe.
      Placental GST activity in chemically exposed women. 18.0 +/- 2.0 mU/mg cytosolic
      protein, was in the range of the lowest obtained values but the differences in
      the placental glutathione status between radioactively contaminated and
      chemically polluted areas point to different pathogenetic mechanisms of this
      reduction. The inverse correlation between the mean values of GSSG-R activities
      and the concentration of low-molecular weight thiols appears to be true for all
      groups. The indices of the placental glutathione status seem to be sensitive to
      environmental pollution.

PMID- 9031957
TI  - Post-partum urinary retention: a comparison between two methods of epidural
      analgesia.
AB  - OBJECTIVE: To compare two methods of epidural labor analgesia regarding the
      incidence of post-partum urinary retention. STUDY DESIGN: One thousand
      parturients who requested epidural analgesia for the relief of labor pain
      received, at random, either bupivacaine 0.25% with adrenaline 1:200 000 (n = 500)
      or bupivacaine 0.125% with 10 micrograms sufentanil (n = 500). During the same
      observation period all women with clinically significant urinary retention (> 500
      ml, requiring indwelling catheter) were registered. RESULT: Altogether 30/3.364
      parturients had clinically significant urinary retention. Twenty-seven of these
      had received epidural analgesia (EDA) (17 with bupivacaine/adrenaline and ten
      with bupivacaine/sufentanil, a non-significant differences). The number of
      parturients with urinary retention was highly increased following EDA (27/1000)
      as compared to those not receiving EDA (3/2364), P < 0.001 (Fisher's exact test).
      In patients with EDA and urinary retention there were no difference between the
      groups in the incidence of instrumental deliveries or vaginal/perirectal tears.
      All parturients regained normal bladder function. CONCLUSION: EDA significantly
      increased the risk of post-partum urinary retention but no difference was found
      between the two epidural techniques.

PMID- 9031958
TI  - Plasma ascorbic acid level and erythrocyte fragility in preeclampsia and
      eclampsia.
AB  - An imbalance between oxidants and antioxidants in the circulation is blamed to
      cause preeclampsia and eclampsia. In this study plasma ascorbic acid level was
      analysed in 13 eclamptic, 14 mild preeclamptic, 12 severe preeclamptic and 20
      uncomplicated pregnancies to see whether there is any correlation with blood
      pressure, proteinuria, serum triglyceride level, erythrocyte fragility and
      leukocyte count. Plasma ascorbic acid level was normal and had no significant
      difference among the groups. Fasting serum triglyceride level was significantly
      higher in the study group than in the control group but it did not differ among
      the three study groups. Erythrocyte fragility was found to be increased in all
      three study groups. Blood leukocyte count was increased in the study groups,
      especially in the eclampsia group. However, plasma ascorbic acid level and
      erythrocyte fragility were found to have no significant correlation with blood
      pressure and proteinuria. It was concluded that though the ascorbic acid levels
      were normal in both the study and the control groups, erythrocyte fragility
      increased probably due to an elevation in peroxide and free radical levels in
      preeclampsia and eclampsia groups, but without any correlation with the severity
      of the clinical picture.

PMID- 9031959
TI  - Automated analysis of antepartum fetal heart rate in relation to fetal rest
      activity states: a longitudinal study of uncomplicated pregnancies using the
      Sonicaid System 8000.
AB  - OBJECTIVES: To learn which fetal heart rate (FHR) parameters change with
      gestational age and to demonstrate the relation with fetal rest-activity states.
      STUDY DESIGN: FHR and fetal movements were recorded in 12 uncomplicated
      pregnancies from 26 weeks gestational age onwards. Seventy-two FHR recordings of
      60 min duration were analysed by a computer (Sonicaid System 8000). Statistical
      analysis of complete 60 min recordings and selective periods of rest and activity
      comprised Spearman's rank correlation test, regression analysis and Wilcoxon's
      signed-rank test. RESULTS: The time needed to meet the system's criteria of
      normality decreased with gestational age. The incidence of accelerations (ACC),
      overall FHR variation (VAR) and variation during 'episodes of high variation'
      (VEHV) increased with gestational age in the total population, but statistical
      significance of these relations could only be demonstrated in a minority of
      individual fetuses. Most FHR parameters differed significantly for periods of
      fetal rest and activity. No FHR parameters showed a relation with gestational age
      during periods of rest. CONCLUSIONS: The increase of ACC, VAR and VEHV with
      gestational age is primarily due to an increase during fetal activity. The
      considerable variation within and between fetuses, however, can only be partly
      explained by fetal rest-activity states.

PMID- 9031960
TI  - Increased maternal plasma levels of soluble adhesion molecules (ICAM-1, VCAM-1, E
      selectin) in preeclampsia.
AB  - The physiological significance of soluble adhesion molecules has not been
      elucidated but it has been reported that a number of cytokines may increase the
      cleavage of soluble adhesion molecules. The fact that preeclampsia is associated
      with both increased cytokine concentrations and endothelial cell damage led us to
      analyse levels of soluble adhesion molecules in preeclamptic women and to compare
      these levels to the disease state. Since the cytokine network is altered by
      reproduction, the present study also raised the question as to whether levels of
      soluble adhesion molecules differ between pregnant and non-pregnant women, and
      whether variations occur with relation to gestational age or delivery. Levels of
      soluble adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1), E-selectin) in 25 preeclamptic women were
      compared to those in healthy pregnant women matched for age, parity and
      gestation, and the levels of soluble adhesion molecules of 40 healthy pregnant
      women at different gestational ages were determined and compared to those of 15
      non-pregnant women. Concentrations were measured by ELISAs. Levels of ICAM-1,
      VCAM-1 and E-selectin concentrations were elevated in preeclamptic pregnancies,
      whereas serum levels in normal pregnancy did not differ from those of non
      pregnant women. No changes were observed in relation to gestational age or
      delivery.

PMID- 9031961
TI  - Rape-related psychotraumatic syndromes.
AB  - OBJECTIVE: This study took place in a forensic center for rape victims. Our aims
      were: first, to explore the longitudinal course of post-traumatic stress disorder
      (PTSD) and prevalence of disorders over the 6-month period following rape, then
      second, to group these disorders into syndromes related to chronic PTSD whilst
      remaining distinct from it, and third, to establish some predictive factors for
      chronic PTSD. STUDY DESIGN: 92 rape victims consecutively admitted to the center
      were regularly interviewed over a 6-month period by a psychiatrist. RESULTS: The
      paper confirms that rape leads to a high proportion of PTSD. Generally speaking,
      the psychopathology following rape is severe. PTSD at 6 months is associated with
      phobic and dissociative disorders. It is further associated with a cluster of
      symptoms arising after rape that we term borderline-like. Incestuous rape is a
      predictive factor for PTSD at 6 months. CONCLUSION: In the aftermath of rape
      several semiologically distinct psychotraumatic syndromes exist.

PMID- 9031962
TI  - Gestational trophoblastic disease following the evacuation of partial
      hydatidiform mole: a review of 66 cases.
AB  - OBJECTIVE: The current study was undertaken in order to identify the clinical
      characteristics and natural history, as well as methods of investigation and
      available therapy, of persistent gestational trophoblastic disease (GTD)
      following the evacuation of partial hydatidiform mole (PM). METHODS: Case reports
      of persistent GTD following the evacuation of partial mole, were searched using
      the Medline computerized retrieval system. There were 66 such cases (including 4
      cases treated at our department), representing 2.9% of GTD following PM. RESULTS:
      The mean age of the women at diagnosis was 28.4 years and mean gravidity was
      2.99. The mean gestational age at diagnosis was 15.5 weeks and the mean uterine
      size was 13.6 weeks. The most common presenting symptom was vaginal bleeding. In
      the majority of the patients, the pre-evacuation diagnosis was incomplete or
      missed abortion. CONCLUSIONS: Although the malignant potential of PM is low,
      persistent GTD may develop after PM and may even metastasize, it is usually
      responsive to single agent chemotherapy but may require combination chemotherapy.
      Therefore, after evacuation of PM, these women should be followed with serial
      serum b-hCG. Further research is needed to enable earlier identification of PM
      that eventually will develop persistent GTD.

PMID- 9031963
TI  - Continuous low dose estradiol released from a vaginal ring versus estriol vaginal
      cream for urogenital atrophy.
AB  - OBJECTIVES: To determine if the efficacy of continuous low dose estradiol
      released from a vaginal ring is equivalent to estriol vaginal cream regarding
      improvement of the patient's subjective feeling of vaginal dryness and to
      determine if there is a preference for either of the two study treatments.
      METHODS: Open-label randomized parallel group trial with active control with a
      blind evaluation of vaginal cytology and with a cross-over (change-over) phase
      for preference comparison. One hundred and sixty five postmenopausal women with
      symptoms of vaginal dryness and signs of vaginal atrophy were randomized to an
      estradiol ring (Estring) or estriol cream (Synapause). The duration of each
      treatment period was 12 weeks. RESULTS: Both study treatments were equally
      effective regarding the ability to alleviate the symptom feeling of vaginal
      dryness and the signs of vaginal atrophy. Both treatments were efficient in
      restoring the vaginal mucosa, recorded as higher maturation values and as
      decreased vaginal pH. Estring was superior to estriol cream regarding preference
      of treatment. Both treatments were equivalent for the occurrence of adverse
      events, including bleeding. CONCLUSION: data from this change-over study confirm
      efficacy and safety of both the vaginal ring and cream in the treatment of
      postmenopausal women with urogenital atrophy symptoms and signs. The patients had
      a strong preference for the vaginal ring.

PMID- 9031964
TI  - Treatment of bowel endometriosis: a report of six cases of colorectal
      endometriosis and a survey of the literature.
AB  - From October 1989 to September 1994, we performed six intestinal resections for
      rectal and sigmoidal endometriosis. The average age of the patients was 32 years
      old, and most had symptoms. In all cases coloscopy showed a normal mucosa.
      Patients had successfully been treated with hormones previously, but had relapsed
      when the treatment was stopped. Bowel resection was segmental, with immediate end
      to end anastomosis in five patients, and partial in one patient. Genital
      endometriosis was diagnosed in three cases and was then treated during the same
      procedure. A low colorectal anastomosis was complicated by a fistula, but no
      recurrence was observed after surgical treatment. Intestinal endometriosis tract
      is in 70% of cases located on the rectosigmoid. An association with genital
      endometriosis tract is observed in 80% of the cases. Deep rectosigmoidal
      endometriosis with symptoms is resistant to hormonal therapy and necessitates a
      surgical treatment by intestinal resection. The pelvis has always to be explored,
      with full evaluation and surgical treatment of genital endometriosis when
      necessary. Appendicular endometriosis should be removed surgically. Postoperative
      treatment can be additionally prescribed in cases of genital endometriosis and
      for leftover digestive location.

PMID- 9031965
TI  - Neutral amino acid transport in placental plasma membrane vesicles in the late
      pregnant rat. Evidence for a B0-like transport system.
AB  - Rat placental plasma membrane vesicles have been used to study both alanine and
      leucine transport at late gestation. The results presented are consistent with
      the presence of more than two separate transport systems for neutral amino acids
      in the rat placenta. One system is clearly Na(+)-independent and transports
      alanine (KM approximately or = 2 mM; Vmax approximately or = 360 pmol ala/mg prot
      x 5 s), leucine (KM approximately or = 0.07 mM; Vmax approximately or = 100 pmol
      leu/mg prot x 5 s), serine, cysteine and 2-amino-2 norbornane carboxylic acid
      (BCH) showing similar properties to the L system, present in many cell types. The
      other systems are Na(+)-dependent and transport alanine (a, KM approximately or =
      5 mM; Vmax approximately or = 3761 pmol ala/mg prot x 5 s; b, KM approximately or
      = 0.07 mM; Vmax approximately or = 376 pmol ala/mg prot x 5 s), cysteine, serine
      and leucine (KM approximately or = 0.2 mM; Vmax approximately or = 112 pmol
      leu/mg prot x 5 s) with different kinetic behaviour referring affinity and
      capacity. While one of them is sensitive to inhibition by methylaminoisobutyric
      acid (MeAIB), the other is a B0-like system similar to that characterized in
      bovine brush-border enterocyte membrane vesicles.

PMID- 9031967
TI  - Prolonged fetal pre-ejection period corrected for PR interval associated with
      cerebral palsy.
AB  - OBJECTIVE: To identify whether the correction of human fetal pre-ejection period
      (PEP) for the effect of catecholamines, as estimated by the PR interval (the
      interval of time measured between the P and R waves of the electrocardiogram
      (ECG)), might improve PEP as a measure of fetal cardiac contractility. METHODS: A
      retrospective analysis of PEP and PR intervals was carried out, using tape
      recordings of fetal ECG and Doppler ultrasound recordings of cardiac valve
      movements, from 43 human fetuses in the first stage of labour. RESULTS: There was
      a strong positive correlation between PEP and PR intervals in the population
      studied: r = 0.641, P < 0.0001, indicating that about 40% of the inter-patient
      variation in PEP could be corrected for by concomitant measurement of the PR
      interval. Only one fetus had markedly prolonged PEP when corrected for PR
      interval. This individual developed cerebral palsy over the first year of life.
      CONCLUSION: Correction of PEP for the effects of catecholamines may greatly
      improve its usefulness in detecting fetal compromise. Combined measurement of the
      PEP and PR interval needs to be evaluated as a technique of fetal monitoring.

PMID- 9031966
TI  - The pregnant ewe: an animal model for fetoscopic surgery.
AB  - OBJECTIVE: To develop an animal model for fetal endoscopic surgery which could be
      feasible and reproducible. The aim of this work was to perform a fetoscopy
      without the need of a laparotomy. METHODS: Pregnant ewes underwent under general
      anesthesia laparoscopy with the creation of a maternal pneumoperitoneum. After
      localizing the placenta by transillumination, we carried out fetoscopy through a
      5 mm trocar using a perfusion of Ringer's solution. RESULTS: Five video-assisted
      procedures have been performed. None of the cases has shown any bleeding from
      myometrial wounds and no suture was necessary. There was no leakage of amniotic
      fluid. Intrauterine space was large enough to manipulate instruments without
      producing any fetal damage. Sharp visualization and anatomical description of the
      fetus were precise without the use CO2. There were no miscarriages and postnatal
      examinations of the lambs were normal. CONCLUSION: Fetoscopic surgery can be
      performed in the pregnant sheep without any complications but preterm labor which
      is the main problem in human fetal surgery, is infrequent in the sheep. Our model
      is reproducible and simulates the surgical endoscopic procedures which will occur
      in a close future in the human species.

PMID- 9031968
TI  - Uncomplicated pregnancy and puerperium after puerperal cerebral venous
      thrombosis.
AB  - In this report we describe an uncomplicated pregnancy and puerperium in a 34 year
      old patient who had a previous puerperal superior sagittal sinus thrombosis.
      Heparin was given 3 weeks antepartum and oral anticoagulants 3 months postpartum.

PMID- 9031986
TI  - Long-term drug treatment of unipolar depression.
AB  - Depression is characterized by a recurrent course in many patients, and as a
      potentially chronic illness. It therefore often requires a long-term treatment
      strategy. This article proposes answers to the questions involved in devising
      such a strategy, using the available literature. Cessation of treatment
      immediately after the observation of a response is associated with a high relapse
      rate, especially within the following 4 months, and all patients should therefore
      be treated for at least 3-6 months after the acute response to secure a stable
      remission. Patients at risk of recurrence should be considered for maintenance
      therapy thereafter. Such patients include those with prior episodes of depression
      within the last 5 years, those with a particularly severe or chronic depressive
      episode, those with residual symptoms scoring HAMD > 8 and also those whose age
      at onset was < 25 or < 60 years. Those who need maintenance therapy are likely to
      need it for a number of years, or indefinitely. SSRIs are better tolerated than
      TCAs or MAOIs and display similar efficacy in acute, continuation and maintenance
      treatment. They are less likely to be fatally toxic if taken in overdosage. There
      is growing evidence to support the use of a full therapeutic dose of
      antidepressant in maintenance treatment.

PMID- 9031987
TI  - 2-Hydroxydesipramine and desipramine plasma levels: how are they related to
      antidepressant response?
AB  - Thirty-six outpatients aged 20 to 51 with RDC primary major depressive disorder
      (MDD) completed a 5-week trial of desipramine following a week of single-blind
      placebo. Five had a past history of hypomanic disorder. For all but one patient,
      daily dosage at bedtime was constant for the final 4 weeks, with a mean (S.D.) of
      168.1 (46.5) mg. Plasma samples drawn at the three final weekly visits were
      assayed by high-performance liquid chromatography for 2-hydroxydesipramine (2-OH
      DMI) and desipramine. Mean (S.D.) plasma levels were 59.8 (30.0) ng/ml for 2-OH
      DMI and 142.9 (138.6) ng/ml for desipramine. Thirteen patients (36%) had a final
      17-item Hamilton depression rating < and = 6 and were classified as responders.
      According to receiver operating characteristics analysis, patients with plasma 2
      OH-DMI levels > and = 58 and < 92 ng/ml had a greater likelihood of responding
      than those with lower or higher levels (p = 0.005, Fisher's exact test), while
      patients with plasma desipramine levels > and = 64 ng/ml were more likely to
      respond than those with lower levels (p = 0.032, Fisher's exact test). Results
      using an alternate response criterion were similar. These findings suggest that
      in desipramine-treated outpatients with primary MDD the relationship between
      therapeutic response and plasma levels is curvilinear for 2-OH-DMI and linear for
      desipramine.

PMID- 9031988
TI  - Benzodiazepine effects on memory tests: dependence on retrieval cues?
AB  - Acute effects of oral flunitrazepam (0.5 and 1 mg), nitrazepam (5 and 10 mg) and
      placebo were assessed on direct (free recall of words and prose, stem-cued
      recall) and indirect (stem and fragment completion) memory tasks. Fifty health
      volunteers took part in this double-blind, independent group study. The relative
      effects of the two benzodiazepines (BZs) on memory revealed a different pattern
      from their effects on alertness, indicating that their amnesic effects are not
      totally secondary to their sedative effects. The higher dose of flunitrazepam
      impaired free recall of words and prose but not cued recall, while neither drug
      affected the two indirect tasks. Differences in drug effects on the direct and
      indirect memory tasks were discussed in terms of resource demands of the various
      tests. We conclude that whether BZs impair performance on memory tasks depends
      more on the cues given at retrieval than the retrieval instructions
      (direct/indirect). The implications for this in terms of BZ amnestic effects are
      drawn out for contextual encoding deficits induced by BZs.

PMID- 9031989
TI  - Aggressive behaviour and extrapyramidal side effects of neuroleptics in
      schizophrenia.
AB  - The objective of this study was to determine whether extrapyramidal side effects
      of neuroleptics are associated with aggressive behaviour in schizophrenia. Thirty
      one physically aggressive patients meeting DSM-III-R criteria for schizophrenia
      were compared with 31 matched non-aggressive patients in relation to their
      extrapyramidal side effects, including drug-induced parkinsonian (DIP) symptoms,
      akathisia and tardive dyskinesia. The aggressive group had significantly more
      severe DIP side effects than the non-aggressive group, but the association
      disappeared when level of psychopathology was controlled for. The aggressive
      group had more severe akathisia than the non-aggressive group, but the difference
      was not statistically significant. The two groups did not suffer in the severity
      of tardive dyskinesia. There was no significant, independent effect of
      extrapyramidal symptoms on aggressive behaviour in our sample of schizophrenic
      patients.

PMID- 9031990
TI  - Antipsychotic drug--a study of the prescription pattern in a total sample of
      patients with a schizophrenic syndrome in one catchment area in the county of
      Uppland, Sweden, in 1991.
AB  - In a total population of patients with a schizophrenic syndrome, the amount of
      antipsychotic drugs during a defined period was studied. Doses of antipsychotics
      were higher in males than in females, low to moderate in most patients, and
      decreased with the duration of illness. There was a significant negative
      correlation between antipsychotic dose and age at first admission. Compulsory
      treatment as well as the use of depot preparations were equally common in both
      sexes. In patients who had been compulsorily admitted, significantly higher doses
      of antipsychotics were used. The amount of antipsychotics prescribed to a single
      patient was best explained by the presence or absence of hallucinations and loose
      associations.

PMID- 9031991
TI  - Fluvoxamine in the treatment of body dysmorphic disorder (dysmorphophobia).
AB  - Fifteen consecutive patients with a DSM-III-R diagnosis of body dysmorphic
      disorder (BDD) were included in a 10-week open clinical trial of fluvoxamine.
      Treatment began at 100 mg/day fluvoxamine and was increased to a maximum of 300
      mg/day or until intolerable side effects developed or a complete or nearly
      complete resolution of symptoms occurred. At baseline and at weeks 2, 6 and 10,
      patients completed the Hopkins Symptoms Check-List (HSCL-90) and a specific
      rating scale for BDD symptoms (BDDSS), and clinicians completed a Clinical Global
      Improvement Scale. Twelve of the 15 patients completed the trial. Of the three
      patients who did not complete the study, one improved moderately during the
      placebo phase, one showed a marked worsening of the depressive symptoms during
      the wash-out phase and one showed adverse side effects, such as nausea and
      diarrhoea, after the first week of treatment and was unable to continue the
      trial. After 10 weeks, of the 12 remaining patients, 10 were considered to be
      markedly improved, one minimally improved and one unchanged. Several outcome
      measures showed a significant improvement from baseline to week 10. Our findings
      suggest that fluvoxamine may be effective in the treatment of BDD. Double-blind
      studies will be required to investigate these findings further.

PMID- 9031992
TI  - Sleep in patients with chronic primary insomnia during long-term zolpidem
      administration and after its withdrawal.
AB  - A double-blind trial was carried out to determine the effect of zolpidem or a
      placebo on sleep in two groups of insomniac patients with a diagnosis of moderate
      chronic primary insomnia. Zolpidem was given at a daily dose of 10 mg for 27
      nights and was preceded (two nights) and followed (three nights) by a placebo.
      Zolpidem induced a significant increase of total sleep time, while total wake
      time and wake time after sleep onset were reduced. Values corresponding to stage
      2 sleep were augmented, while stage 3 sleep and REM sleep showed no significant
      changes. Tolerance did not develop during the zolpidem administration period, and
      rebound insomnia did not show following abrupt interruption of drug
      administration. In addition, patients on zolpidem had a more peaceful sleep with
      no decrement of levels of alertness.

PMID- 9031994
TI  - Phasic craving for carbohydrate observed with citalopram.
AB  - The serotonin selective reuptake inhibitors (SSRIs) have clinically and
      ancedotally been associated with nausea and weight loss as a side effect of their
      action. The tricyclic antidepressants have been linked to carbohydrate (CHO)
      craving and weight gain in patients with major depressive disorders. This side
      effect has been attributed to the strong anti-histaminergic actions of these
      agents and is recognized as a causal factor of non-compliance in a substantial
      percentage of patients. CHO craving is an important feature and complication of
      the treatment of depression and is often ignored. A total of 18 patients were
      treated with the SSRI citalopram in our mood disorder clinic. In eight cases
      there was a significant increase in CHO craving together with weight gain shortly
      after initiation of treatment. The craving for CHO took on a phasic presentation.
      These cases are presented, together with data on the change in mood and anxiety
      symptom rating scales. Our observations appear paradoxical, given that serotonin
      (5-HT) typically mediates a reduction in CHO intake and that citalopram displays
      potent and select 5-HT-enchancing actions. However, the receptor binding profile
      of citalopram may predict a risk for inducing this adverse event. These, together
      with serotonergic, dopaminergic, histaminergic and other possible mechanisms are
      discussed. A profound influence on patient acceptability was observed, suggesting
      that the impact on compliance needs to be considered.

PMID- 9031997
TI  - Tranylcypromine in recurrent brief depression: two case reports.
AB  - Two cases are described in which patients with recurrent brief depression
      experienced a noticeable therapeutic response with the first generation monoamine
      oxidase inhibitor tranylcypromine. These reports are of interest in light of
      recent data suggesting that this subtype of depression does not respond to
      conventional antidepressants such as selective serotonin reuptake inhibitors.

PMID- 9031993
TI  - The effect of clozapine on the course of illness in chronic schizophrenia: focus
      on treatment outcome in out-patients.
AB  - Forty-eight consecutive schizophrenic patients treated with clozapine (mean daily
      dose 436 mg) for at least 1 year (mean 7.6, range 2.2-14.8 years) were studied
      retrospectively. The most favourable changes in the course of illness were
      observed in 39 out-patients, whose duration of hospitalization per year
      continuously and significantly declined after the introduction of clozapine. The
      out-patients who continued with clozapine treatment for more than 10 years (n =
      8) did not need hospitalization at all during the last year of the observation
      period. The improvement in social functioning in the out-patient group correlated
      positively with the duration of clozapine medication (r = 0.384, p = 0.016) and
      with the duration of hospitalization (r = 0.372, p = 0.020) after introduction of
      clozapine. Out-patients with disorganized schizophrenia (later called hebephrenic
      according to the Finish version of DSM-III) showed more noticeable clinical (U =
      226, p = 0.032) and social (U = 233, p = 0.024) improvements than non-hebephrenic
      patients. There appears to be a subgroup of hebephrenic patients who benefit from
      clozapine more than patients with other types of schizophrenia.

PMID- 9031996
TI  - Severe withdrawal akathisia following neuroleptic discontinuation successfully
      controlled by clozapine.
AB  - Akathisia is one of the most distressing side effects of neuroleptic treatment.
      It is usually managed by manipulating the neuroleptic dose and administering anti
      akathisic compounds (beta-blockers, anticholinergics, serotonin antagonists).
      However, the pathophysiological background of withdrawal akathisia which follows
      the discontinuation of neuroleptic treatment remains unclear, and there is as yet
      no adequate treatment. We report a case of severe withdrawal akathisia associated
      with suicidal and autoaggressive behaviour during a gradual transition from
      perphenazine/trihexyphenidyl to clozapine. The akathisia was effectively managed
      by titration of clozapine (maximum dose 200 mg/day) Thereafter, reduction of the
      clozapine dose resulted in a recurrence of the akathisia, and the resumption of
      clozapine dose was accompanied by full amelioration of symptoms. We suggest that
      the antiserotonergic properties of clozapine were responsible for its anti
      akathisic effect. Differences in the treatment of acute and withdrawal types of
      akathisia are emphasized.

PMID- 9031995
TI  - Effects of nemonapride on positive and negative symptoms of schizophrenia.

PMID- 9031998
TI  - A case of serotonin syndrome induced by concomitant treatment with low-dose
      trazodone and amitriptyline and lithium.
AB  - We describe a patient treated with trazodone, amitriptyline and lithium carbonate
      who developed anxiety, restlessness, tremor, myoclonus, hyperreflexia,
      diaphoresis, rigidity and hyperthermia. The constellation of findings was
      diagnostic of serotonin syndrome. Although doses of trazodone and amitriptyline
      were relatively low, serotonin syndrome developed in this patient. It is
      suggested that the combination with lithium facilitated the effect of central
      serotonergic responses mediated by trazodone and amitriptyline.

PMID- 9031999
TI  - New developments in obsessive-compulsive disorder research: implications for
      clinical management.
AB  - Over the past decade, epidemiological, phenomenological, pharmacological,
      neurobiological, brain imaging and genetic research has contributed to a
      substantial change in our understanding of obsessive-compulsive disorder (OCD).
      Once regarded as a rare psychodynamic illness, OCD is now recognized as a common
      condition affecting 2-3% of the population. Better recognition combined with the
      demonstrated efficacy of serotonin reuptake inhibitors, such as clomipramine and
      the selective serotonin reuptake inhibitors (SSRIs), has dramatically improved
      the prognosis of this disorder, which exacts a considerable personal and economic
      burden. While the aetiology is still not understood, increasingly sophisticated
      research techniques are enabling us to begin to uncover the underlying
      pathophysiology of this illness. This paper reviews some of the recent
      developments which have enhanced our understanding of OCD and considers their
      potential impact on clinical management.

PMID- 9032000
TI  - Refining treatment approaches in obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) has emerged as a common but frequently hidden
      psychiatric disorder which inflicts an intolerable burden on sufferers and
      demands effective management. For many years, however, OCD was considered
      treatment resistant and it is only in the past 15 years that effective therapy
      has become available. The discovery that the symptoms of OCD could be controlled
      with clomipramine, but not with other tricyclic antidepressants, was a crucial
      step in the development of effective management of the condition. The ability of
      clomipramine to treat OCD derives from its potency as an inhibitor of serotonin
      reuptake. Serotonin reuptake inhibition has become the fundamental requirement
      for the pharmacological management of OCD. In the past decade selective serotonin
      reuptake inhibitors (SSRIs) have been shown to be effective in the management of
      OCD. Meta-analysis comparing the efficacy of clomipramine and SSRIs initially
      suggest that clomipramine is more effective than SSRIs, but changes in the
      clinical characteristics of trial populations over time indicate that the meta
      analyses may be misleading. In the few direct comparisons of SSRIs and
      clomipramine, the two treatments have in fact proved equally effective. Attention
      is now shifting to the impact side effects on efficacy, a particularly important
      consideration for OCD patients who require long-term medication but are
      frequently reluctant to take drugs. The limited data available suggest that SSRIs
      are better tolerated than clomipramine and are therefore more likely to lead to a
      favourable treatment outcome.

PMID- 9032001
TI  - Long-term management of obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a chronic debilitating condition that
      requires long-term treatment. The selective serotonin reuptake inhibitors (SSRIs)
      appear to be associated with similar levels of efficacy to clomipramine in short
      term treatment, but to have significant tolerability advantages. The results of
      the long-term controlled studies on clomipramine, fluvoxamine, fluoxetine and
      sertraline are reviewed. They demonstrate a significantly better outcome for anti
      obsessional drugs than placebo. The absence of adequate long-term controlled
      studies on pharmacotherapy strengthen the grounds for recommending
      pharmacotherapy as the optimal approach for long-term treatment of OCD. The SSRIs
      would appear to be the treatment of choice in OCD in view of their tolerability
      and safety advantages compared with clomipramine.

PMID- 9032002
TI  - Pharmacokinetic drug interaction potential of selective serotonin reuptake
      inhibitors.
AB  - Obsessive-compulsive disorder (OCD) is a chronic disorder requiring long-term
      treatment. The pharmacological management of the disorder, therefore, requires
      the use of agents which, in addition to being efficacious and well tolerated, are
      unlikely to cause pharmacokinetic drug-drug interactions with concomitantly
      administered medication which the patient is receiving or may receive in the
      future. The selective serotonin reuptake inhibitors (SSRIs) have similar
      pharmacodynamic profiles but their pharmacokinetic profiles are very different.
      Perhaps the most substantial pharmacokinetic difference among these drugs is in
      their potential for drug-drug interactions via the inhibition of cytochrome P450
      (CYP) isoenzymes. This review provides comprehensive background information on
      these enzyme systems and discusses their significance with respect to the optimal
      care of patients. Fluoxetine is a substantial inhibitor of CYP2D6, has mild
      effects on CYP3A3/4, and may also have effects on CYP2C9/10 and CYP2C19. Effects
      on drugs metabolized by these enzymes can persist for many weeks after fluxoetine
      discontinuation due to the long half-life of fluoxetine and its active metabolite
      norfluoxetine. Fluvoxamine is a substantial inhibitor of CYP1A2 and CYP2C19, and
      a moderate inhibitor of CYP3A3/4. Paroxetine is a substantial inhibitor of
      CYP2D6. In contrast, sertraline and citalopram are mild inhibitors of CYP2D6 at
      their usually effective doses and are not known to produce clinically meaningful
      inhibition of any other isoenzymes. However, citalopram has not been well studied
      against all of these enzymes, especially in vivo. An increased risk of
      pharmacokinetic drug interactions is the immediate clinical consequence of the
      inhibitory effects of these drugs on CYP isoenzymes. However, with the emphasis
      on long-term treatment, particularly in chronic conditions such as OCD, it will
      also be important to determine the long-term clinical consequences of
      substantially inhibiting specific CYP isoenzymes with those SSRIs which have
      these effects. Thus knowledge of the substrates and inhibitors of CYP isoenzymes
      may help clinicians to anticipate and avoid pharmacokinetic drug interactions and
      may better define rational prescribing practices.

PMID- 9032003
TI  - New developments in behaviour therapy for obsessive-compulsive disorder.
AB  - Effective behaviour therapy techniques of exposure and response (or ritual)
      prevention for obsessive-compulsive disorder (OCD) are based on the principle of
      habituation. This is a common-sense approach that is simple in conception but not
      easy to implement and maintain. Controlled trials have proven the short- and long
      term effectiveness of behaviour therapies in OCD and meta-analyses suggest that
      behaviour therapy is at least as effective as potent serotonin reuptake
      inhibitors (SRIs). A combination of these behavioural and psychopharmacological
      modalities might represent the optimal treatment for OCD. Here I review behaviour
      therapy techniques for OCD, the studies supporting its effectiveness and
      acceptability and problems limiting its wider dissemination. The preliminary
      results of a computer-administered behaviour therapy programme for OCD, BT STEPS,
      are also presented.

PMID- 9032004
TI  - Obsessive-compulsive disorder-related disorders: the role of selective
      serotonergic reuptake inhibitors.
AB  - Obsessive-compulsive spectrum disorders comprise a unique category of related
      disorders with important diagnostic, aetiological and therapeutic implications.
      This group of disorders may overlap with obsessive-compulsive disorder (OCD) in
      symptomatic profile, demographics, family history, neurobiology, comorbidity,
      clinical course and response to selective anti-obsessional behavioural and
      pharmacotherapies. OCD-related disorders can be viewed along a continuum with
      risk avoidance on the compulsive end and risk seeking at the other. This
      dimension may be defined within a framework which relates hyperfrontality and
      increased serotonergic sensitivity with compulsive disorders and hyperfrontality
      and low presynaptic serotonergic levels with impulsive disorders. Most biological
      models of OCD-related disorders stress the importance of serotonin in their
      pathophysiology and these disorders have also been shown to be preferentially
      responsive to selective serotonergic reuptake inhibitors (SSRIs). This paper
      reviews the management of the OCD spectrum and the evidence for efficacy of the
      SSRIs and the differential treatment responses of the compulsive and impulsive
      disorders with regard to therapeutic dosage, response lag time and maintenance of
      symptom remission.

PMID- 9032005
TI  - Obsessive-compulsive disorder: adding value to treatment through patient support
      groups.
AB  - The development of effective medications (serotonin reuptake inhibitor
      antidepressants) and the widespread use of behavioural therapy (exposure and
      response prevention) have greatly improved the treatment options for patients
      with obsessive-compulsive disorder (OCD). Despite these advances, less than 20%
      of patients with OCD are receiving treatment. One of the main reasons for this is
      the lack of patient access to treatment. OCD support groups serve as a vehicle to
      decrease the social isolation experienced by individuals with OCD. They also
      serve as the doorway to treatment and the starting point on the path of recovery
      through educating patients about treatment and motivating them to re-enter
      treatment. There are currently four different types of OCD support groups. This
      paper gives an appraisal of each group, with emphasis on their aims, attractions
      and pitfalls. In addition, it provides insight into the resources available to
      help mental health professionals to better understand the needs of individuals
      with OCD.

PMID- 9032007
TI  - An MLP-based model for identifying qEEG in depression.
AB  - Manual differentiation of electroencephalography (EEG) paper recordings in cases
      of depression is not very helpful. So, a Multilayer Perceptron (MLP) has been
      used to differentiate the EEG power density spectra (qEEG) in the wakeful state
      from animals (control, exercised and depressed). The qEEG ranging from 1 to 30
      Hz, at 1 Hz increments (30 input features) and also a slow, medium and fast
      activity (represented by three ranges of frequencies at the input) were used.
      After training with depressed and control qEEG only, the MLP has been found to
      distinguish successfully between the normal and the depressed rats in more than
      80% of the cases, identifying, in the process, most of the exercised groups' EEG
      as normal. The reduction in the dimension of input features from 30 individual
      frequencies to 3 frequency bands has produced similar results. The rules
      generated for making such distinctions have been found to be similar to the
      clinical views.

PMID- 9032006
TI  - Guidelines for cost-effective implementation of Picture Archiving and
      Communication Systems. An approach building on practical experiences in three
      European hospitals.
AB  - This paper describes a comprehensive approach for the assessment of the impact of
      (partial) Picture Archiving and Communication Systems (PACS). The approach is
      developed, based on actual clinical experience in three European hospitals and
      tested in these environments. The approach departs from a thorough analysis of
      the working procedures and information flows before implementation, both
      descriptive and quantitative. On the basis of this analysis, quantitative (and
      hence testable) objectives of the implementation are defined. The implementation
      strategy is defined after comparison of various scenarios, taking costs and
      effects for both the final and the transition phases into account. The approach
      is supported by a comprehensive evaluation protocol and a software package
      (PACER). The approach is demonstrated in this paper by applying it on a
      hypothetical PACS implementation for CT, ultrasound and for the part of the
      radiology department serving ICU. The objectives of this PACS are: (1)--to
      shorten the turn around time between the radiology department and ICU from 4 h to
      30 min, (2)--to save 2000 m2 of film per year and (3)--to save personnel time. In
      this case the PACS is introduced in three phases and completed after three years.
      The cost analysis shows that, if started in 1995, a financial break even point is
      reached after 6 years, when comparing costs for the film-based system with those
      of the PACS. Experiences in the three sites show that the approach helps to
      harvest potential benefits, allowing a cost-effective implementation of PACS.

PMID- 9032008
TI  - Methodology for using the UMLS as a background knowledge for the description of
      surgical procedures.
AB  - The Unified Medical Language System (UMLS) contains and organizes a large number
      of terms from a variety of biomedical terminology systems. This study examines
      the relevance of the UMLS content and structures to the specific purpose of the
      conceptual representation of medical procedures. The MAOUSSC modelling is a
      compositional formalism with a description of elementary procedures in terms of
      elementary concept entities and combinations of such descriptions into more
      complex ones. The UMLS knowledge base is expected to provide semantically
      categorized medical concepts and interconcept relations. A method to reuse the
      UMLS has been developed. Quantitative and qualitative results are presented. Some
      difficulties in reusing the UMLS as a background knowledge are related to the
      preeminence of some terminology sources and to the instanciation of interconcept
      links. Other ones suggest that purpose-independence in categorization cannot be
      achieved.

PMID- 9032009
TI  - A comparison of neural network and Bayes recognition approaches in the evaluation
      of the brainstem trigeminal evoked potentials in multiple sclerosis.
AB  - This article describes the application of Multi-Layer Perceptron (MLP),
      Probabilistic Neural Network and Kohonen's Learning Vector Quantization to the
      problem of diagnosing Multiple Sclerosis. The classification information is
      obtained from brainstem trigeminal evoked potential. The performance of the
      neural networks based classifiers is compared with that of the human experts and
      the Bayes classifier. The ability of the MLP classifier to generalize is far
      better than that of the Bayes classifier. The efficiency of the neural network
      based classifiers in conjunction with several types of well-known evoked
      potential features, such as Fourier transform space, latency and temporal wave,
      is examined. Although a large clinical data base would be necessary, before this
      approach can be fully validated, the initial results are promising.

PMID- 9032010
TI  - Segmentation of auditory brainstem response signals.
AB  - Auditory brainstem responses are used to detect hearing defects in audiology and
      otoneurology. The use of computer programs for the analysis of such recordings is
      increasing. To identify their detailed properties a pattern recognition algorithm
      implemented in an analysis program must be highly reliable. For the recognition
      process, some preprocessing phases after recording the necessary, such as
      filtering and often also segmentation. In the following, we will explore
      segmentation, which can be used in preprocessing of biomedical signals after
      filtering. We studied linear segmentation, where slopes of short signal segments
      are computed and divided into different classes according to their values. A
      segment length of 8 samples for a sampling frequency of 50 kHz employed was best
      according to our tests and error criteria. Using clustering, we found that less
      than 10 segment classes is suitable for pattern recognition.

PMID- 9032011
TI  - Nonlinear eye movement detection method for drowsiness studies.
AB  - Automatic long-term vigilance analysis systems require information about the
      occurrence and type of eye movements, in addition to information about other
      physiological signals. This paper presents a method to detect different types of
      eye movements in ambulatory recordings. The method is based on the application of
      a weighted FIR-median-hybrid filter in the preprocessing of the signal and on the
      novel use of linear correlation between two EOG signals which are obtained using
      a new, improved electrode montage. The evaluation of the method showed that it
      performed well in detecting isolated unambiguous eye movements, but differences
      were observed in comparison to visual scoring in borderline cases. The method was
      found to be suitable for use as part of a signal analysis system for drowsiness
      studies.

PMID- 9032012
TI  - X-chromosome activity: impact of imprinting and chromatin structure.
AB  - The analysis of the imprinting of the X chromosome has provided insight into
      factors that affect the initiation and the choice of the chromosome for
      inactivation in the early mammalian embryo (Lyon, 1996). There are significant
      differences in the chromatin configuration, methylation and gene expression
      between Xi and Xa in somatic cells. Preferential paternal X inactivation that is
      concomitant with widespread heterochromatinization first occurs in the
      trophectoderm in the blastocyst. It is now clear that the activity of some
      paternal X-linked genes are suppressed before this stage. In the epiblast there
      may be early preferential paternal X inactivation before a random pattern
      supersedes. These observations suggest that parent-specific modification of the
      chromosome may determine the choice of which X chromosome is to be inactivated
      (Lyon, 1996). Differential methylation within the Xist gene or the XIC may lead
      to imprinted X-chromosome behavior. Alternatively, we postulate that imprinting
      of the X chromosome may be related to differences in chromatin configuration of
      the X chromosome in male and female germ cells which may then influence X-linked
      gene expression in the early embryo (Fig. 4). This may occur with a gene by gene
      effect leading to suppression of paternal alleles. An overall chromatin
      difference in the chromosomes may influence imprinted paternal Xist expression in
      early embryos and in the trophectoderm and primary endoderm populations that
      segregate early from the totipotent progenitors. Alternatively more specific
      differences in the chromatin architecture of the Xist gene or other gene loci in
      the Xic may constitute the signature of the imprint.

PMID- 9032013
TI  - Coexpression of HNF-3 beta and Isl-1/2 and mixed distribution of ventral cell
      types in the early neural tube.
AB  - Pattern formation in the vertebrate ventral neural tube has been proposed to
      depend on the ability of notochord-derived signals to induce the differentiation
      of distinct cell types in a distance-dependent manner. To determine whether the
      distribution of early differentiating cell types in the ventral neural tube is
      consistent with the operation of such a mechanism in vivo, the early localization
      of Isl-1/2+ motor neurons in relation to HNF-3 beta+ floor plate cells has been
      investigated. In the most immature regions of the caudal spinal cord of early rat
      and chick embryos, an initial mixed distribution of cell types was detected that
      develops into a distribution characteristic of the final embryonic pattern where
      different cell types are found at distinct locations. In addition, a number of
      cells that coexpress both markers are detected within the floor plate. At later
      stages, coexpression is also detected in the hindbrain in the boundary region
      between HNF-3 beta+ ventricular cells and Isl-1/2+ motor neurons. The mixed
      distribution of early differentiating cells expressing HNF-3 beta and Isl-1/2 and
      the coexpression of these markers in single cells within the floor plate suggest
      that secondary cellular interactions are important in the generation of the final
      embryonic pattern of the neural tube.

PMID- 9032014
TI  - Isolation of a novel chick homolog of Serrate and its coexpression with C-Notch-1
      in chick development.
AB  - Intercellular signaling mediated by the transmembrane proteins, Notch as receptor
      and its ligands, Delta and Serrate, plays essential roles in the developmental
      fate decision of many cell types in Drosophila. The Notch genes are highly
      conserved both in invertebrates and in vertebrates, suggesting that Notch pathway
      regulates cell fate decisions during vertebrates development. Notch, Delta and
      Serrate homologs in chicken have been cloned (Henrique et al., Nature 375: 787
      790, 1995; Myat et al., Dev. Biol. 174: 233-247, 1996). We isolated a novel chick
      homolog of Drosophila Serrate, named C-Serrate-2, and examined its expression
      patterns during the early chick development using whole-mount in situ
      hybridization. C-Serrate-2 transcripts were detected in several tissues including
      the forebrain, the myotome and the apical ectodermal ridge (AER) of the limb bud
      of a 4-day-old chick embryo. In most of the regions where C-Serrate-2 was
      expressed, C-Notch-1 was also expressed. Our observations suggest that Serrate-2
      Notch-1 signaling plays a role in a variety of morphogeneses during the chick
      development.

PMID- 9032016
TI  - Genesis of newt sperm axial fiber: cDNA cloning and expression of a 29 kDa
      protein, a major component of the axial fiber, during spermatogenesis.
AB  - Newt sperm has a unique structure: the tail consists of axial fiber, undulating
      membrane and flagellum. The genesis and chemical composition of the axial fiber
      remain unknown. The axial fiber consists of about 10 major components, as
      evidenced by SDS-polyacrylamide gel electrophoresis. In order to clarify the
      biochemical properties of the components of the axial fiber and study the
      mechanism of axial fiber formation, we focused our attention on a 29 kDa protein,
      the major constituent of the axial fiber. Immunofluorescent antibody technique
      showed that the 29 kDa protein was first expressed in the cytoplasm of early
      round spermatids but was expressed on fibers in the periphery of the cyst in late
      round spermatids. Double staining with tubulin antibody and 29 kDa antibody
      showed that the fibers around the cysts in early round spermatids were flagella
      alone but those in late round spermatids consisted of flagella and 29 kDa
      protein. These results indicated that 29 kDa proteins are synthesizsed in the
      cytoplasm of round spermatids and enter the preformed flagella in late round and
      elongated spermatids. A cDNA clone for 29 kDA protein was isolated. A database
      search could not find any homologous clones, indicating that the 29 kDa protein
      is a new one. Northern blot with the cDNA showed that mRNA for 29 kDa protein was
      highly expressed in round spermatids but barely in primary spermatocytes,
      indicating that the mRNA for 29 kDa protein is haploid-expressed.

PMID- 9032015
TI  - Expression of c-ets-1 and uPA genes is associated with mammary epithelial cell
      tubulogenesis or neoplastic scattering.
AB  - Although the inductive interactions which trigger epithelial morphogenesis have
      been extensively described, little is known about the transcription factors
      involved in these processes. During mammary gland morphogenesis, we report the
      expression of the transcription factor c-ets-1 and one of its target genes uPA in
      mesenchymal cells during early stages of epithelial invasion, and later in
      epithelial cells themselves. In vitro studies show that both c-ets-1 and uPA
      mRNAs can be induced in cultured normal mammary epithelial cells in response to
      medium conditioned by MRC-5 fibroblasts. In contrast, invasive tumorigenic cell
      lines from the mammary epithelium express constitutively c-ets-1 and uPA while
      non-invasive tumorigenic cells do not. In three dimensional co-cultures in
      collagen gels, a preferential expression of these genes is detected in epithelial
      cells migrating through the gel either at the tips of normal ducts or in
      cancerous cells which are scattering. These genes are also expressed in the
      neighboring fibroblasts. In MRC-5 fibroblasts, conditioned media from tumorigenic
      epithelial cells induce more efficiently c-ets-1 and uPA mRNA accumulation than
      do conditioned medium from normal cells. These results suggest that epithelial
      mesenchymal interactions trigger c-ets-1 and uPA expression in both compartments
      during mammary gland morphogenesis. The expression of the genes correlates with
      invasiveness of epithelial cells irrespective of their being normal or cancerous.

PMID- 9032018
TI  - Competition-based head versus foot decision in chimeric hydras.
AB  - The decision head versus foot in a regenerating fragment of Hydra has been
      proposed to result from long-range competition for resources such as head
      specific precursor cells and hormonal factors, with the winning end of the body
      column forming the head and the losing end forming the foot. The present study
      presents new experimental support for this hypothesis. Chimeras prepared from two
      strains of Hydra magnipapillata with high and low capacity for head regeneration
      reveal that the low capacity of reg-16 to regenerate a head resides in a low
      ability to recruit head-promoting resources. When confronted with competing wt105
      tissue taken from the same body region, reg-16 tissue is caused to form feet
      while wt105 is enabled to from enlarged heads which sometimes split into two.
      Triplet chimeras prepared with labeled donor animals and two competing unlabeled
      recipients indicate that head-forming wt105 tissue incorporates migrating cells
      more effectively then head-forming reg-16 tissue.

PMID- 9032019
TI  - Ameloblastin expression in rat incisors and human tooth germs.
AB  - We recently identified ameloblastin as an ameloblast-specific gene product from a
      rat incisor cDNA library (Krebsbach et al., J. Biol. Chem. 271: 4431-4435, 1996).
      Here we report the developmental pattern of expression of ameloblastin in rat
      incisors and human tooth germs as visualized by in situ hybridization and
      immunochemistry. Compared to the expression of amelogenin, the major ameloblast
      product, ameloblastin mRNA was more widely expressed in ameloblasts from the
      presecretory to the late maturation stage of development. Ameloblastin mRNA was
      first observed in the juxtanuclear cytoplasm or presecretory stage ameloblasts,
      gradually increased in the distal cytoplasm of secretory stage ameloblasts and
      was found throughout the cytoplasm of early to late maturation stage ameloblasts.
      The immunostaining of ameloblastin, using a monospecific antibody raised against
      a recombinant protein, showed intense reactivity in Tomes' processes of secretory
      stage ameloblasts and surrounding enamel. The immunoreaction was concentrated in
      the juxtanuclear cytoplasm of late maturation stage ameloblasts. High-resolution
      colloidal gold immunocytochemistry established the presence of ameloblastin
      antigenicity in the Golgi apparatus, secretory granules in Tomes' process and
      enamel. Human tooth germs in early to late bell stage also expressed ameloblastin
      mRNA and ameloblastin antigenicity in the ameloblasts. Western blot analysis of
      protein extracts from rat incisor tissues indicated that ameloblastin can be
      found in the enamel epithelial tissue and in mineralized enamel, as well as in
      the EDTA decalcification solution. These data indicate that ameloblastin is an
      ameloblast secretory product which is sequentially expressed from the
      presecretory to the late maturation stage in rat and human teeth. This unique
      developmental pattern suggests that ameloblastin may have a broader role in
      amelogenesis than amelogenin and tuftelin.

PMID- 9032020
TI  - Lateral and radial growth uncoupled in reaggregated retinospheroids of embryonic
      avian retina.
AB  - According to an earlier resented model (Layer and Willbold, Int. Rev. Cytol. 146:
      1-47, 1993), growth of the retina can be conceived of as an areal increase of an
      epithelial tissue sheet ("lateralization") plus a concomitant establishment of
      the layered retina ("radialization"). To provide further support for this model,
      here we have reaggregated dissociated retinal plus pigmented cells from chick or
      quail embryos and observed their development into histotypic three-dimensional
      spheres in rotation culture. These so-called stratospheroids consist of a
      continuous fully laminated retinal part with a coiled-up pigmented epithelial
      core. Using BrdU-labeling, we show that radial growth, i.e. the sequential
      production of cell types in spheroids, is comparable to normal vitreal-scleral
      retinogenesis. The region next to the pigmented epithelial core represents a
      "lateral growth zone" (equivalent to an ora serrata in vivo), where mitotic cell
      numbers are highest, even when in the laminated part proliferation has already
      ceased. Gradients of lateral differentiation emanate from this growth zone into
      the retinal tissue, as revealed by immunostaining of the photoreceptor protein
      opsin and the cell recognition molecule F11. Moreover, we found that
      stratospheroids derived from older embryos consist only of a hollow monolayered
      neuroepithelium which develops in the absence of any radial growth. This
      indicates that cell production is sustained longer in lateral than in radial
      direction. These differently staged stratospheroids will be excellent models to
      characterize genes involved in the regulation of lateral and radial growth
      processes.

PMID- 9032021
TI  - Regeneration of lower and upper jaws in urodeles is differentially affected by
      retinoic acid.
AB  - The vitamin A derivative retinoic acid (RA) is a powerful teratogen which can
      induce severe craniofacial and limb malformations if administered at certain
      stages of gestation. In addition this compound has been shown to affect
      patterning in regenerating systems. A classical example is the induction of
      supernumerary structures along the proximodistal axis of the regenerating
      amphibian limb. We have investigated the effect of RA on other regenerating
      systems, the amphibian lower and upper jaws, both in developing and adult
      animals. We report here that RA does not induce formation of extra structures
      either in the lower or in the upper jaw of adult newts under experimental
      conditions where duplications of the regenerating limb occur. However, RA
      selectively induces severe malformations in the upper jaw regenerate that
      resemble those induced in avian and mammalian embryos. Analysis of the expression
      of the newt retinoic acid receptors RAR alpha and delta in upper and lower jaws
      showed that RAR alpha was expressed at a significant level in the wound
      epidermis, but not in blastemal cells, whereas no RAR delta could be detected in
      the regenerate either by in situ hybridization or by using an anti-RAR delta
      antibody. Therefore, unlike in the limb, in jaws RAR delta is not up-regulated
      following amputation, and this difference in expression may be causally related
      to the different effects induced by RA on jaws and limbs. In order to establish
      whether retinoids affected regeneration of developing jaws in a similar fashion,
      their effects were studied in animals whose jaws had been amputated at different
      developmental stages. Under the experimental conditions used overall growth
      retardation and head defects were observed in the majority of embryos which had
      been amputated and treated with retinol palmitate (RP) between stages 26-28 and
      38-39. In contrast, patterning of upper jaw regenerates in larvae amputated at
      stage 26-28 and 38-39. In contrast, patterning of upper jaw regenerates in larvae
      amputated at stage 45 was not significantly affected by the treatment, although
      the early phase of regeneration was slower than in controls. The different
      responses to retinoids of regenerating facial structures in embryos, larvae and
      adults will be discussed.

PMID- 9032017
TI  - Head formation at the basal end and mirror-image pattern duplication in Hydra
      vulgaris.
AB  - Head and foot in Hydra are organizing centers and considered to be sources of
      long-range inhibitory morphogens that prevent head and foot formation elsewhere.
      In a previous study the apparent long-range head inhibition was shown to coincide
      with long-range foot promotion exerted by the head. Here it is shown that: (1)
      ring-shaped pieces of the body column taken from a near-foot position form feet -
      frequently circular - if inserted into the midgastric region; this ectopic foot
      formation is strongly dependent on assistance by the head. (2) Bisection causes a
      transient increase in positional value at the wounded basal end of the upper body
      column. This transient development in the head direction in turn promotes ectopic
      foot formation by transplants and thus has an effect as though the source of a
      foot-inhibiting morphogen were removed. The existence of long-range foot
      inhibition is open to question. (3) If a ring with low positional value is
      present in the midgastric region, the increase in positional value at the basal
      end is stable and results in mirror-image head formation instead of foot
      regeneration in up to 100% of cases. Even before the ring forms a foot it acts
      like a ligature and subdivides the body column into two developmental
      compartments. (4) The basal head in turn organizes a mirror-image duplication of
      the body pattern. In pattern regulation, Hydra follows rules of intercalation
      known from other organisms.

PMID- 9032022
TI  - Interphase-like chromatin configuration induced by cycloheximide in maturing pig
      oocytes: effects of protein phosphatase inhibitors.
AB  - Embryo cloning methods could greatly benefit from the manipulation of cell cycle
      in oocytes from large domestic mammals. The present study was undertaken to
      examine the effects of the protein synthesis inhibitor cycloheximide and the
      inhibitors of protein phosphatases 1 and 2A okadaic acid and calyculin A on
      maturing pig oocytes. Cycloheximide treatment (10 micrograms/ml) induced an
      interphase-like chromatin configuration (ICC) in maturing oocytes. Up to 69% of
      the oocytes exhibited ICC when treated with cycloheximide after 24 h of in vitro
      culture. ICC starts to appear after a 4 h exposure to cycloheximide and the ICC
      percentage reached its plateau after 12 h of cycloheximide treatment. ICC is
      fully reversible. The addition of okadaic acid (0.5 microM) inhibited the ICC in
      cycloheximide-treated maturing oocytes and allowed the completion of maturation
      in 55% of them. In oocytes with ICC, the immunocytochemistry for tubulin revealed
      the rearrangement of microtubule into an interphase meshwork and these oocytes
      lost their ability to induce tubulin assembly, as shown after short-time taxol
      treatment. The addition of okadaic acid prevented this microtubule rearrangement
      and preserved a certain level of tubulin assembly. Calyculin appeared to be more
      effective than okadaic acid in the prevention of ICC. It is concluded that de
      novo protein synthesis is necessary during a certain period of meiotic maturation
      for the maintenance of metaphase chromatin configuration in pig oocytes. This
      protein (or proteins) acts through the inhibition of endogenous protein
      phosphatases, probably protein phosphatase of 2A type.

PMID- 9032023
TI  - Differential localization of Mox-1 and Mox-2 proteins indicates distinct roles
      during development.
AB  - Transcript localizations for Mox genes have implicated this homeobox gene
      subfamily in the early steps of mesoderm formation. We have extended these
      studies by determining the protein expression profile of Mox-1 and Mox-2 during
      mouse development. The time of onset of Mox protein expression has been
      accurately obtained to provide clues as to their roles during gastrulation.
      Expression of Mox-1 protein is first detected in the newly formed mesoderm of
      primitive streak stage mouse embryos (7.5 days post-coitum, d.p.c.). In contrast,
      Mox-2 protein is first detected at 9.0 d.p.c. in thr already formed somites.
      Additionally, immunostaining reveals new and distinct areas of Mox expression in
      the branchial arches and limbs that were not reported in our previous mRNA
      localization analysis. Mouse Mox-2 antibodies cross-react specifically in similar
      embryonic tissues in chick indicating the conservation of function of Mox genes
      in vertebrates. These expression data suggest that the Mox genes function
      transiently in the formation of mesodermal and mesenchymal derivatives, after
      their initial specification, but before their overt differentiation. Furthermore,
      while there appears to be some overlap in protein expression between Mox-1 and
      Mox-2 during somitogenesis, unique areas of expression indicate several distinct
      roles for the Mox genes during development.

PMID- 9032024
TI  - Developmental expression of splicing variants of fibroblast growth factor
      receptor 3 (FGFR3) in mouse.
AB  - A characteristic feature of the fibroblast growth factor receptor (FGFR) family
      is the structural diversity generated by alternative splicing. The FGFR3 gene
      encodes two splice variants because of the mutually exclusive use of the exons
      IIIb and IIIc. In the present study we examined the expression of the two
      different splice forms IIIb and IIIc of FGFR3 in developing mouse embryos (12
      days p.c., 14 days p.c., 20 days p.c.). The overall level of the IIIc exon splice
      product surpassed that of the IIIb exon form. The IIIc mRNA was detected in the
      developing brain and in the spinal cord. Outside the nervous system very strong
      expression was observed in the vertebra and in all other bony structures. In
      contrast, the IIIb splice form was restricted to epithelial structures with no
      expression detected in the central nervous system and bone.

PMID- 9032025
TI  - The chick embryo chorioallantoic membrane as a model for in vivo research on
      angiogenesis.
AB  - The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane
      that is commonly used in vivo to study both new vessel formation and its
      inhibition in response to tissues, cells, or soluble factors. Quantitative or
      semiquantitative methods may be used to evaluate the amount of angiogenesis and
      anti-angiogenesis. Thanks to the CAM system, angiogenesis could be investigated
      in association with normal, inflammatory and tumor tissues, and soluble factors
      inducing angiogenic or anti-angiogenic effects could be identified. Rabbit cornea
      provides an alternative in vivo system, but CAM appears to be easier to handle
      and less expensive. Moreover, CAM can be used with very few limitations.

PMID- 9032045
TI  - Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The
      Inhaled Nitric Oxide Study Group.
AB  - BACKGROUND: Persistent pulmonary hypertension of the newborn causes systemic
      arterial hypoxemia because of increased pulmonary vascular resistance and right
      to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary
      vascular resistance in newborns. We studied whether inhaled nitric oxide
      decreases severe hypoxemia in infants with persistent pulmonary hypertension.
      METHODS: In a prospective, multicenter study, 58 full-term infants with severe
      hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe
      either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed
      with oxygen from a ventilator. If oxygenation increased after 20 minutes and
      systemic blood pressure did not decrease, the treatment was considered successful
      and was continued at lower concentrations. Otherwise, it was discontinued and
      alternative therapies, including extracorporeal membrane oxygenation, were used.
      RESULTS: Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of
      30 infants (53 percent), whereas conventional therapy without inhaled nitric
      oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term
      therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of
      the infants who had initial improvement. Extracorporeal membrane oxygenation was
      required in 71 percent of the control group and 40 percent of the nitric oxide
      group (P=0.02). The number of deaths was similar in the two groups. Inhaled
      nitric oxide did not cause systemic hypotension or increase methemoglobin levels.
      CONCLUSIONS: Inhaled nitric oxide improves systemic oxygenation in infants with
      persistent pulmonary hypertension and may reduce the need for more invasive
      treatments.

PMID- 9032047
TI  - Mutations in the sarcoglycan genes in patients with myopathy.
AB  - BACKGROUND: Some patients with autosomal recessive limb-girdle muscular dystrophy
      have mutations in the genes coding for the sarcoglycan proteins (alpha-, beta-,
      gamma-, and delta-sarcoglycan). To determine the frequency of sarcoglycan-gene
      mutations and the relation between the clinical features and genotype, we studied
      several hundred patients with myopathy. METHODS: Antibody against alpha
      sarcoglycan was used to stain muscle-biopsy specimens from 556 patients with
      myopathy and normal dystrophin genes (the gene frequently deleted in X-linked
      muscular dystrophy). Patients whose biopsy specimens showed a deficiency of alpha
      sarcoglycan on immunostaining were studied for mutations of the alpha-, beta-,
      and gamma-sarcoglycan genes with reverse transcription of muscle RNA, analysis
      involving single-strand conformation polymorphisms, and sequencing. RESULTS:
      Levels of alpha-sarcoglycan were found to be decreased on immunostaining of
      muscle-biopsy specimens from 54 of the 556 patients (10 percent); in 25 of these
      patients no alpha-sarcoglycan was detected. Screening for sarcoglycan-gene
      mutations in 50 of the 54 patients revealed mutations in 29 patients (58
      percent): 17 (34 percent) had mutations in the alpha-sarcoglycan gene, 8 (16
      percent) in the beta-sarcoglycan gene, and 4 (8 percent) in the gamma-sarcoglycan
      gene. No mutations were found in 21 patients (42 percent). The prevalence of
      sarcoglycan-gene mutations was highest among patients with severe (Duchenne-like)
      muscular dystrophy that began in childhood (18 of 83 patients, or 22 percent);
      the prevalence among patients with proximal (limb-girdle) muscular dystrophy with
      a later onset was 6 percent (11 of 180 patients). CONCLUSIONS: Defects in the
      genes coding for the sarcoglycan proteins are limited to patients with Duchenne
      like and limb-girdle muscular dystrophy with normal dystrophin and occur in 11
      percent of such patients.

PMID- 9032046
TI  - Bone mass and the risk of breast cancer among postmenopausal women.
AB  - BACKGROUND: Recent studies have shown a direct relation between serum estrogen
      levels assessed at a single point in time and the risk of breast cancer, but no
      evidence links estrogen levels assessed repeatedly over an extended interval to
      the risk of breast cancer. Bone mass has been proposed as a marker of cumulative
      exposure to estrogen in women. We therefore studied the association between bone
      mass and the incidence of breast cancer. METHODS: Between 1967 and 1970, 1373
      women who were 47 to 80 years old and had no history of breast cancer underwent
      posteroanterior hand radiography in the Framingham Study. We used radiogrametry
      to measure the cortical width of each woman's second metacarpal. Participants
      were followed until the end of 1993. All incident cases of breast cancer were
      confirmed by pathological reports. We used a Cox proportional-hazards model to
      examine the relation of metacarpal bone mass to the risk of postmenopausal breast
      cancer. RESULTS: Postmenopausal breast cancer developed in 91 subjects. Incidence
      rates per 1000 person-years increased from 2.0 among the women in the lowest age
      specific quartile of metacarpal bone mass to 2.6, 2.7, and 7.0 among the women in
      the second, third, and highest quartiles, respectively. After adjustments for age
      and other potential confounding factors, the rate ratios for the risk of breast
      cancer were 1.0, 1.3, 1.3, and 3.5 from the lowest quartile to the highest (P for
      trend, <0.001). CONCLUSIONS: Women in the highest quartile of bone mass are at
      higher risk for postmenopausal breast cancer than those in the lowest quartile.
      The mechanisms underlying this relation are not understood, but cumulative
      exposure to estrogen may play a part.

PMID- 9032048
TI  - Images in clinical medicine. Traumatic ventricular aneurysm.

PMID- 9032049
TI  - Blunt trauma to the heart and great vessels.

PMID- 9032050
TI  - Seminars in medicine of the Beth Israel Deaconess Medical Center. Insulin-like
      growth factors.

PMID- 9032051
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 7-1997. A 14-year-old girl with recurrent painless rectal
      bleeding.

PMID- 9032052
TI  - The muscular dystrophies--clarity or chaos?

PMID- 9032053
TI  - Withdrawing intensive life-sustaining treatment -- recommendations for
      compassionate clinical management.

PMID- 9032054
TI  - Lac repressor-operator complex.
AB  - For many years the lac operon of Escherichia coli has been the paradigm for gene
      regulation. Recently, the structures of the lac repressor core bound to isopropyl
      beta-D-1-thiogalactoside (IPTG), the intact apo lac repressor, the intact lac
      repressor complexes with IPTG and a 21-base-pair symmetric operator, and the
      refined headpiece of the repressor have been determined. These structures have
      provided a framework for understanding a wealth of biochemical and genetic
      information. An analysis of these structures, as well as a description of their
      function and a comparison to homologous proteins, is now possible.

PMID- 9032055
TI  - The prion folding problem.
AB  - Prion diseases are neurodegenerative disorders in which dramatic conformational
      change in the structure of the prion protein is the fundamental event. This
      structural transition involves the loss of substantial alpha-helical content and
      the acquisition of beta-sheet structure. A convergence of recent biological and
      structural studies argues that the mechanism underlying the prion diseases is
      truly unprecedented.

PMID- 9032056
TI  - The ternary complex of EF-Tu and its role in protein biosynthesis.
AB  - The past year has seen a breakthrough in our structural understanding of how
      aminoacyl-tRNAs are selected and transported to the ribosomal A-site in order to
      decode genetic information contained in messenger RNA. All aminoacyl-tRNAs are
      recognized by the elongation factor EF-Tu in prokaryotes or EF-1alpha in
      eukaryotes. The recent determination of the structure of the ternary complex of
      aminoacyl-tRNA, EF-Tu and a GTP analogue shows how the CCA end of all aminoacyl
      tRNA structures can be accommodated in a specific binding site on EF-Tu-GTP, and
      how part of the T-helix can be recognized by EF-Tu in a non-sequence-specific
      way. Furthermore, the structure of the ternary complex shows striking structural
      similarity to the structure of another prokaryotic elongation factor, EF-G, the
      tRNA translocase, in its GDP or empty form. This observation has led to the
      proposal of a general macromolecular mimicry of RNA and protein, which predicts
      elements of RNA-like structures will occur in other translation factors, such as
      initiation factors and release factors, that interact with similar sites on the
      ribosome.

PMID- 9032057
TI  - Protein structure: what is it possible to predict now?
AB  - The computational techniques of sorting out protein folds (these techniques
      include dynamic programming, self-consistent field theory, etc.) have already
      ceased to be the bottleneck of predictions. The main problem is that all the
      methods of recognition and prediction of protein structure can actually use only
      some part of the interactions operating in the chain, and that even their
      energies are not known precisely. This is the principal source of errors now. The
      errors can be reduced by employment of many distant homologues, but this opens a
      possibility to predict a generalized folding pattern rather than a particular
      fold with all its details.

PMID- 9032058
TI  - DNA-repair enzymes.
AB  - Recent crystallographic studies of DNA-repair enzymes have provided the
      structural basis for the recognition of damaged DNA. The results imply that
      flipping out of the base is a common and crucial event in DNA repair. Two classes
      of repair enzymes that recognize distinct types of damage may exist. DNA-repair
      enzymes that share similar folds and DNA binding motifs have been proposed to
      belong to a superfamily.

PMID- 9032059
TI  - Making DNA do a U-turn: IHF and related proteins.
AB  - IHF and HU belong to a family of proteins that introduce sharp bends into DNA and
      act as accessory factors in a variety of cellular processes in prokaryotes. In
      addition to the crystal structure of IHF bound to DNA, the past year has seen a
      number of advances in the understanding of the interactions of these proteins
      with DNA in solution.

PMID- 9032060
TI  - Physical basis of a protein-DNA recognition code.
AB  - Can a stereochemical recognition code explain sequence-specific protein-nucleic
      acid interactions? Whereas a code that is generally applicable to DNA-binding
      proteins of all known structural families is unattainable, the indications are
      that a code can describe at least some of the interactions of classical zinc
      fingers with DNA. The crystal structures of related zinc finger-DNA complexes
      reveal a remarkable mode of interaction that sets the framework for this code,
      and recent biochemical studies have elucidated the intermolecular contacts
      (contingent on this framework) that result in specificity.

PMID- 9032061
TI  - Theoretical studies of protein-folding thermodynamics and kinetics.
AB  - Recently, protein-folding models have advanced to the point where folding
      simulations of protein-like chains of reasonable length (up to 125 amino acids)
      are feasible, and the major physical features of folding proteins, such as
      cooperativity in thermodynamics and nucleation mechanisms in kinetics, can be
      reproduced. This has allowed deep insight into the physical mechanism of folding,
      including the solution of the so-called 'Levinthal paradox'.

PMID- 9032062
TI  - Kinetic role of early intermediates in protein folding.
AB  - The traditional view that partly folded intermediates are important for directing
      a protein toward the native state has been challenged by the notion that proteins
      can intrinsically fold rapidly in a single step if kinetic complications due to
      slow conformational events are avoided. Intermediates that accumulate within the
      first few milliseconds of folding are, however, a common observation even for
      small single-domain proteins. Recent spectroscopic studies, coupled with
      quantitative kinetic analysis, suggest that folding is facilitated by the rapid
      formation of compact intermediates with some native-like structural features.

PMID- 9032063
TI  - The role of water in protein-DNA interactions.
AB  - It is becoming well accepted that water plays an important role in both the
      specificity and affinity of protein-DNA interactions. Recently, a combination of
      structural, biochemical and thermodynamic techniques has particularly enhanced
      our understanding of the role of water in complexes between DNA and three
      different proteins: the trp repressor; the homeodomain; and the glucocorticoid
      receptor DNA-binding domain.

PMID- 9032064
TI  - Chaperone-assisted protein folding.
AB  - Molecular chaperones of the Hsp70 and chaperonin families are basic constituents
      of the cellular machinery that mediates protein folding. Recent functional and
      structural studies corroborate existing models for the mechanism of these
      components. Highlights of the past year include the X-ray crystallographic
      analysis of the peptide-binding domain of the Escherichia coli Hsp70 homolog,
      DnaK, the direct demonstration of protein folding in the central cavity of the
      chaperonin GroEL, and the visualization of conformational changes in GroEL during
      the chaperonin folding cycle.

PMID- 9032065
TI  - Histone-like transcription factors in eukaryotes.
AB  - Histone proteins have long been recognized as important regulators of eukaryotic
      gene expression. Condensation of DNA into chromatin by the core (H2A, H2B, H3,
      H4) and linker (H1, H5) histones effectively represses transcription initiation
      from the promoters of genes that have been packaged. Recently, eukaryotic
      transcriptional activators and coactivators (both positive and negative)
      resembling core and linker histone proteins have been discovered. Substantial
      progress has been made on structural and mechanistic studies of histones and
      histone-like transcription factors. Three-dimensional structures solved include
      the core histone octamer, an archael histone homodimer, two core histone-like
      subunits of transcription factor IID, a linker histone, and a linker histone-like
      transcriptional activator.

PMID- 9032066
TI  - Nucleation mechanisms in protein folding.
AB  - Experiment and theory are converging on the importance of nucleation mechanisms
      in protein folding. These mechanisms do not use classic nuclei, which are well
      formed elements of structure present in ground states, but they use diffuse,
      extended regions, which are observed in transition states.

PMID- 9032067
TI  - Submillisecond kinetics of protein folding.
AB  - New experimental methods permit observation of protein folding and unfolding on
      the previously inaccessible nanosecond-microsecond timescale. These studies are
      beginning to establish times for the elementary motions in protein folding -
      secondary structure and loop formation, local hydrophobic collapse, and global
      collapse to the compact denatured state. They permit an estimate of about one
      microsecond for the shortest time in which a protein can possibly fold.

PMID- 9032068
TI  - Protein-nucleic acid interactions.

PMID- 9032069
TI  - Folding and binding. From theory to therapy.

PMID- 9032070
TI  - Web alert. Folding and binding. Protein-nucleic acid interactions.

PMID- 9032071
TI  - The crystal structure of the flavin containing enzyme dihydroorotate
      dehydrogenase A from Lactococcus lactis.
AB  - BACKGROUND: . Dihydroorotate dehydrogenase (DHOD) is a flavin mononucleotide
      containing enzyme, which catalyzes the oxidation of (S)-dihydroorotate to
      orotate, the fourth step in the de novo biosynthesis of pyrimidine nucleotides.
      Lactococcus lactis contains two genes encoding different functional DHODs whose
      sequences are only 30% identical. One of these enzymes, DHODA, is a highly
      efficient dimer, while the other, DHODB, shows optimal activity only in the
      presence of an iron-sulphur cluster containing protein with which it forms a
      complex tetramer. Sequence alignments have identified three different families
      among the DHODs: the two L. lactis enzymes belong to two of the families, whereas
      the enzyme from E. coli is a representative of the third. As no three-dimensional
      structures of DHODs are currently available, we set out to determine the crystal
      structure of DHODA from L. lactis. The differences between the two L. lactis
      enzymes make them particularly interesting for studying flavoprotein redox
      reactions and for identifying the differences between the enzyme families.
      RESULTS: . The crystal structure of DHODA has been determined to 2.0  resolution.
      The enzyme is a dimer of two crystallographically independent molecules related
      by a non-crystallographic twofold axis. The protein folds into and alpha/beta
      barrel with the flavin molecule sitting between the top of the barrel and a
      subdomain formed by several barrel inserts. Above the flavin isoalloxazine ring
      there is a small water filled cavity, completely buried beneath the protein
      surface and surrounded by many conserved residues. This cavity is proposed as the
      substrate-binding site. CONCLUSIONS: . The crystal structure has allowed the
      function of many of the conserved residues in DHODs to be identified: many of
      these are associated with binding the flavin group. Important differences were
      identified in some of the active-site residues which vary across the distinct
      DHOD families, implying significant mechanistic differences. The substrate
      cavity, although buried, is located beneath a highly conserved loop which is much
      less ordered than the rest of the protein and may be important in giving access
      to the cavity. The location of the conserved residues surrounding this cavity
      suggests the potential orientation of the substrate.

PMID- 9032073
TI  - The crystal structure of a triacylglycerol lipase from Pseudomonas cepacia
      reveals a highly open conformation in the absence of a bound inhibitor.
AB  - BACKGROUND: . Lipases, a family of enzymes which catalyze the hydrolysis of
      triglycerides, are widely distributed in many organisms. True lipases are
      distinguished from esterases by the characteristic interfacial activation they
      exhibit at an oil-water interface. Lipases are one of the most frequently used
      biocatalysts for organic reactions performed under mild conditions. Their
      biotechnological applications include food and oil processing and the preparation
      of chiral intermediates for the synthesis of enantiomerically pure
      pharmaceuticals. Recent structural studies on several lipases have provided some
      clues towards understanding the mechanisms of hydrolytic activity, interfacial
      activation, and stereoselectivity. This study was undertaken in order to provide
      structural information on bacterial lipases, which is relatively limited in
      comparison to that on the enzymes from other sources. RESULTS: . We have
      determined the crystal structure of a triacylglycerol lipase from Pseudomonas
      cepacia (PcL) in the absence of a bound inhibitor using X-ray crystallography.
      The structure shows the lipase to contain an alpha/beta-hydrolase fold and a
      catalytic triad comprising of residues Ser87, His286 and Asp264. The enzyme
      shares several structural features with homologous lipases from Pseudomonas
      glumae (PgL) and Chromobacterium viscosum (CvL), including a calcium-binding
      site. The present structure of PcL reveals a highly open conformation with a
      solvent-accessible active site. This is in contrast to the structures of PgL and
      PcL in which the active site is buried under a closed or partially opened 'lid',
      respectively. CONCLUSIONS: . PcL exhibits some structural features found in other
      lipases. The presence of the Ser-His-Asp catalytic triad, an oxyanion hole, and
      the opening of a helical lid suggest that this enzyme shares the same mechanisms
      of catalysis and interfacial activation as other lipases. The highly open
      conformation observed in this study is likely to reflect the activated form of
      the lipase at an oil-water interface. The structure suggests that the interfacial
      activation of bacterial lipases involves the reorganization of secondary
      structures and a large movement of the lid to expose the active site. This is
      similar to the mechanism described for other well characterized fungal and
      mammalian lipases.

PMID- 9032072
TI  - A new structural class of serine protease inhibitors revealed by the structure of
      the hirustasin-kallikrein complex.
AB  - BACKGROUND: Hirustasin belongs to a class of serine protease inhibitors
      characterized by a well conserved pattern of cysteine residues. Unlike the
      closely related inhibitors, antistasin/ghilanten and guamerin, which are
      selective for coagulation factor Xa or neutrophil elastase, hirustasin binds
      specifically to tissue kallikrein. The conservation of the pattern of cysteine
      residues and the significant sequence homology suggest that these related
      inhibitors possess a similar three-dimensional structure to hirustasin. RESULTS:
      The crystal structure of the complex between tissue kallikrein and hirustasin was
      analyzed at 2.4  resolution. Hirustasin folds into a brick-like structure that is
      dominated by five disulfide bridges and is sparse in secondary structural
      elements. The cysteine residues are connected in an abab cdecde pattern that
      causes the polypeptide chain to fold into two similar motifs. As a hydrophobic
      core is absent from hirustasin the disulfide bridges maintain the tertiary
      structure and present the primary binding loop to the active site of the
      protease. The general structural topography and disulfide connectivity of
      hirustasin has not previously been described. CONCLUSIONS: The crystal structure
      of the kallikrein-hirustasin complex reveals that hirustasin differs from other
      serine protease inhibitors in its conformation and its disulfide bond
      connectivity, making it the prototype for a new class of inhibitor. The disulfide
      pattern shows that the structure consists of two domains, but only the C-terminal
      domain interacts with the protease. The disulfide pattern of the N-terminal
      domain is related to the pattern found in other proteins. Kallikrein recognizes
      hirustasin by the formation of an antiparallel beta sheet between the protease
      and the inhibitor. The P1 arginine binds in a deep negatively charged pocket of
      the enzyme. An additional pocket at the periphery of the active site accommodates
      the sidechain of the P4 valine.

PMID- 9032075
TI  - A conserved infection pathway for filamentous bacteriophages is suggested by the
      structure of the membrane penetration domain of the minor coat protein g3p from
      phage fd.
AB  - BACKGROUND: . Gene 3 protein (g3p), a minor coat protein from bacteriophage fd
      mediates infection of Escherichia coli bearing an F-pilus. Its N-terminal domain
      (g3p-D1) is essential for infection and mediates penetration of the phage into
      the host cytoplasm presumbly through interaction with the Tol complex in the E.
      coli membranes. Structural knowledge of g3p-D1 is both important for a molecular
      understanding of phage infection and of biotechnological relevance, as g3p-D1
      represents the primary fusion partner in phage display technology. RESULTS: . The
      solution structure of g3p-D1 was determined by NMR spectroscopy. The principal
      structural element of g3p-D1 is formed by a six-stranded beta barrel
      topologically identical to a permutated SH3 domain but capped by an additional N
      terminal alpha helix. The presence of structurally similar domains in the related
      E. coli phages, lke and 12-2, as well as in the cholera toxin transducing phage
      ctx&phi; is indicated. The structure of g3p-D1 resembles those of the recently
      described PTB and PDZ domains involved in eukaryotic signal transduction.
      CONCLUSIONS: . The predicted presence of similar structures in membrane
      penetration domains from widely diverging filamentous phages suggests they share
      a conserved infection pathway. The widespread hydrogen-bond network within the
      beta barrel and N-terminal alpha helix in combination with two disulphide bridges
      renders g3p-D1 a highly stable domain, which may be important for keeping phage
      infective in harsh extracellular environments.

PMID- 9032074
TI  - The open conformation of a Pseudomonas lipase.
AB  - BACKGROUND: . The interfacial activation of lipases results primarily from
      conformational changes in the enzymes which expose the active site and provide a
      hydrophobic surface for interaction with the lipid substrate. Comparison of the
      crystallization conditions used and the structures observed for a variety of
      lipases suggests that the enzyme conformation is dependent on solution
      conditions. Pseudomonas cepacia lipase (PCL) was crystallized in conditions from
      which the open, active conformation of the enzyme was expected. Its three
      dimensional structure was determined independently in three different
      laboratories and was compared with the previously reported closed conformations
      of the closely related lipases from Pseudomonas glumae (PGL) and Chromobacterium
      viscosum (CVL). These structures provide new insights into the function of this
      commercially important family of lipases. RESULTS: . The three independent
      structures of PCL superimpose with only small differences in the mainchain
      conformations. As expected, the observed conformation reveals a catalytic site
      exposed to the solvent. Superposition of PCL with the PGL and CVL structures
      indicates that the rearrangement from the closed to the open conformation
      involves three loops. The largest movement involves a 40 residue stretch, within
      which a helical segment moves to afford access to the catalytic site. A
      hydrophobic cleft that is presumed to be the lipid binding site is formed around
      the active site. CONCLUSIONS: . The interfacial activation of Pseudomonas lipases
      involves conformational rearrangements of surface loops and appears to conform to
      models of activation deduced from the structures of fungal and mammalian lipases.
      Factors controlling the conformational rearrangement are not understood, but a
      comparison of crystallization conditions and observed conformation suggests that
      the conformation of the protein is determined by the solution conditions, perhaps
      by the dielectric constant.

PMID- 9032076
TI  - A good turn for DNA: the structure of integration host factor bound to DNA.
AB  - The crystal structure of integration host factor (IHF) complexed with DNA shows
      how a small heterodimeric protein can induce a big bend in DNA. IHF exerts
      leverage in the minor groove and wraps DNA around the body of the protein,
      providing another example of sequence-specific recognition of the minor groove.

PMID- 9032077
TI  - New structure--novel fold?

PMID- 9032079
TI  - Not just another Fab: the crystal structure of a TcR-MHC-peptide complex.
AB  - The structure of a ternary complex formed between a T-cell receptor, a major
      histocompatibility complex (MHC) protein and a viral peptide provides new
      insights into the cellular immune response. The results provide a molecular basis
      for understanding the development of T cells and the reactions leading to
      transplant rejection and autoimmunity.

PMID- 9032078
TI  - Structure of a human lysosomal sulfatase.
AB  - BACKGROUND: . Sulfatases catalyze the hydrolysis of sulfuric acid esters from a
      wide variety of substrates including glycosaminoglycans, glycolipids and
      steroids. There is sufficient common sequence similarity within the class of
      sulfatase enzymes to indicate that they have a common structure. Deficiencies of
      specific lysosomal sulfatases that are involved in the degradation of glycosamino
      glycans lead to rare inherited clinical disorders termed mucopolysaccharidoses.
      In sufferers of multiple sulfatase deficiency, all sulfatases are inactive
      because an essential post-translational modification of a specific active-site
      cysteine residue to oxo-alanine does not occur. Studies of this disorder have
      contributed to location and characterization of the sulfatase active site. To
      understand the catalytic mechanism of sulfatases, and ultimately the determinants
      of their substrate specificities, we have determined the structure of N
      acetylgalactosamine-4-sulfatase. RESULTS: . The crystal structure of the enzyme
      has been solved and refined at 2.5  resolution using data recorded at both 123K
      and 273K. The structure has two domains, the larger of which belongs to the
      alpha/beta class of proteins and contains the active site. The enzyme active site
      in the crystals contains several hitherto undescribed features. The active-site
      cysteine residue, Cys91, is found as the sulfate derivative of the aldehyde
      species, oxo-alanine. The sulfate is bound to a previously undetected metal ion,
      which we have identified as calcium. The structure of a vanadate-inhibited form
      of the enzyme has also been solved, and this structure shows that vanadate has
      replaced sulfate in the active site and that the vanadate is covalently linked to
      the protein. Preliminary data is presented for crystals soaked in the
      monosaccharide N-acetylgalactosamine, the structure of which forms a product
      complex of the enzyme. CONCLUSIONS: . The structure of N-acetylgalactosamine-4
      sulfatase reveals that residues conserved amongst the sulfatase family are
      involved in stabilizing the calcium ion and the sulfate ester in the active site.
      This suggests an archetypal fold for the family of sulfatases. A catalytic role
      is proposed for the post-translationally modified highly conserved cysteine
      residue. Despite a lack of any previously detectable sequence similarity to any
      protein of known structure, the large sulfatase domain that contains the active
      site closely resembles that of alkaline phosphatase: the calcium ion in sulfatase
      superposes on one of the zinc ions in alkaline phosphatase and the sulfate ester
      of Cys91 superposes on the phosphate ion found in the active site of alkaline
      phosphatase.

PMID- 9032080
TI  - Crystal structure of the dihaem cytochrome c4 from Pseudomonas stutzeri
      determined at 2.2A resolution.
AB  - BACKGROUND: . Cytochromes c4 are dihaem cytochromes c found in a variety of
      bacteria. They are assumed to take part in the electron-transport systems
      associated with both aerobic and anaerobic respiration. The cytochrome c4
      proteins are located in the periplasm, predominantly bound to the inner membrane,
      and are able to transfer electrons between membrane-bound reduction systems and
      terminal oxidases. Alignment of cytochrome c4 sequences from three bacteria,
      Pseudomonas aeruginosa, Pseudomonas stutzeri and Azotobacter vinelandii, suggests
      that these dihaem proteins are composed of two similar domains. Two distinctly
      different redox potentials have been measured for the Ps. stutzeri cytochrome c4,
      however. RESULTS: . The crystal structure of the dihaem cytochrome c4 from Ps.
      stutzeri has been determined to 2.2A resolution by isomorphous replacement. The
      model, consisting of two entire cytochrome c4 molecules and 138 water molecules
      in the asymmetric unit, was refined to an R value of 20.1% for all observations
      in the resolution range 8-2.2A. The molecule is organized in two cytochrome c
      like domains that are related by a pseudo-twofold axis. The symmetry is virtually
      perfectly close to the twofold axis, which passes through a short hydrogen bond
      between the two haem propionic acid groups, connecting the redox centre of each
      domain. This haem-haem interaction is further stabilized by an extensive
      symmetrical hydrogen-bond network. The twofold symmetry is not present further
      away from the axis, however, and the cytochrome c4 molecule can be considered to
      be a dipole with charged residues unevenly distributed between the two domains.
      The haem environment in the two domains show pronounced differences, mainly on
      the methionine side of the haem group. CONCLUSIONS: . The structure, in
      conjunction with sequence alignment, suggests that the cytochrome protein has
      evolved by duplication of a cytochrome c gene. The difference in charge
      distribution around each haem group in the two domains allows the haem group in
      the N-terminal domain to be associated with the lower redox potential of 241 mV
      and the C-terminal haem group with the higher potential of 328 mV. The molecular
      dipole characteristic of cytochrome c4 is important for its interaction with, and
      recognition of, its redox partners. In cytochrome c4, the hydrogen-bond network
      (between residues that are conserved in all known cytochrome c4 subspecies) seems
      to provide an efficient pathway for an intramolecular electron transfer that can
      ensure cooperativity between the two redox centres. The C-pyrrole corners of the
      haem edges are potential sites for external electron exchange.

PMID- 9032081
TI  - The structure of an energy-coupling protein from bacteria, IIBcellobiose, reveals
      similarity to eukaryotic protein tyrosine phosphatases.
AB  - BACKGROUND: . The bacterial phosphoenolpyruvate-dependent phosphotransferase
      system (PTS) mediates the energy-driven uptake of carbohydrates and their
      concomitant phosphorylation. In addition, the PTS is intimately involved in the
      regulation of a variety of metabolic and transcriptional processes in the
      bacterium. The multiprotein PTS consists of a membrane channel and at least four
      cytoplasmic proteins or protein domains that sequentially transfer a phosphoryl
      group from phosphoenolpyruvate to the transported carbohydrate. Determination of
      the three-dimensional structure of the IIB enzymes within the multiprotein
      complex would provide insights into the mechanisms by which they promote
      efficient transport by the membrane channel IIC protein and phosphorylate the
      transported carbohydrate on the inside of the cell. RESULTS: . The crystal
      structure of the IIB enzyme specific for cellobiose, IIBcellobiose (molecular
      weight 11.4 kDa), has been determined to a resolution of 1.8  and refined to an R
      factor of 18.7% (Rfree of 24. 1%). The enzyme consists of a single four-stranded
      parallel beta sheet flanked by helices on both sides. The phosphorylation site
      (Cys 10) is located at the C-terminal end of the first beta strand. No positively
      charged residues, which could assist in phosphoryl-transfer, can be found in or
      near the active site. The fold of IIBcellobiose is remarkably similar to that of
      the mammalian low molecular weight protein tyrosine phosphatases. CONCLUSIONS: .
      A comparison between IIBcellobiose and the structurally similar low molecular
      weight protein tyrosine phosphatases provides insight into the mechanism of the
      phosphoryltransfer reactions in which IIBcellobiose is involved. The differences
      in tertiary structure and active-site composition between IIBcellobiose and the
      glucose-specific IIBglucose give a structural explanation why the carbo-hydrate
      specific components of different families cannot complement each other.

PMID- 9032082
TI  - Structures of a hemoglobin-based blood substitute: insights into the function of
      allosteric proteins.
AB  - BACKGROUND: . Potential blood substitutes can be based on hemoglobin. Two
      problems must be overcome with acellular hemoglobin-based blood substitutes,
      however: the oxygen affinity of purified human hemoglobin is too high for it to
      deliver oxygen to tissues, and hemoglobin tetramers dissociate into alphabeta
      dimers that can cause kidney damage. A modified form of hemoglobin, rHb 1.1, has
      reduced oxygen affinity as the result of an Asnbeta 108-->Lys mutation, and
      dimerization is prevented by the insertion of a glycine residue between the
      sequences of the normal alpha chains to produce one covalently continuous di
      alpha-chain. Determination of the structure of rHb 1.1 would provide structure
      based explanations for the altered properties of rHb 1.1. RESULTS: . We
      determined the structures of the deoxy form of rHb 1.1 at 2.0  resolution and of
      cyanomet-rHb 1.1 at 2.6  resolution. Deoxy-rHb 1.1 adopts the classic 'T state'
      quaternary structure, but cyanomet-rHb 1.1 adopts a novel quanternary structure,
      the B state. The most striking feature of the tertiary structures is a charged
      hydrogen bond involving Lysbeta 108 that is broken in the T-->B state transition.
      The glycine bridge within the di-alpha-chain is well defined in both structures
      and appears to cause adoption of the B state instead of the previously observed
      ligand-bound quaternary structures R or Y/R2. CONCLUSIONS: . A charged hydrogen
      bond between Lysbeta 108 and Tyrbeta35 is broken in the transition between the
      deoxy and ligand-bound forms of rHb 1.1. This structural change reduces the
      oxygen affinity of rHb 1.1 by changing the relative stability of deoxy and ligand
      bound states. Furthermore, our observations highlight the importance of small
      conformational changes in allosteric proteins, even in their most rigid domains.
      Three ligand-bound quaternary structures of hemoglobin (R, Y/R2 and B) have now
      been described. In contrast, only one quaternary structure has been observed for
      deoxyhemoglobin (T). The structural degeneracy of the high oxygen affinity form
      of hemoglobin is an important reminder that allosteric proteins may have multiple
      quaternary structures that are functionally very similar. This degeneracy of
      quaternary structures has important implications for the regulation of allosteric
      proteins, because different quaternary structures may be stabilized by different
      allosteric effectors.

PMID- 9032083
TI  - Barley lipid-transfer protein complexed with palmitoyl CoA: the structure reveals
      a hydrophobic binding site that can expand to fit both large and small lipid-like
      ligands.
AB  - BACKGROUND: . Plant nonspecific lipid-transfer proteins (nsLTPs) bind a variety
      of very different lipids in vitro, including phospholipids, glycolipids, fatty
      acids and acyl coenzyme As. In this study we have determined the structure of a
      nsLTP complexed with palmitoyl coenzyme A (PCoA) in order to further our
      understanding of the structural mechanism of the broad specificity of these
      proteins and its relation to the function of nsLTPs in vivo. RESULTS: . 1H and
      13C nuclear magnetic resonance spectroscopy (NMR) have been used to study the
      complex between a nsLTP isolated from barley seeds (bLTP) and the ligand PCoA.
      The resonances of 97% of the 1H atoms were assigned for the complexed bLTP and
      nearly all of the resonances were assigned in the bound PCoA ligand. The
      palmitoyl chain of the ligand was uniformly 13C-labelled allowing the two ends of
      the hydrocarbon chain to be assigned. The comparison of a subset of 20 calculated
      structures to an average structure showed root mean square deviations of 1.89 +/-
      0.19  for all C, N, O, P and S atoms of the entire complex and of 0.57 +/- 0.09 
      for the peptide backbone atoms of the four alpha helices of the complexed bLTP.
      The four-helix topology of the uncomplexed bLTP is maintained in the complexed
      form of the protein. The bLTP only binds the hydrophobic parts of PCoA with the
      rest of the ligand remaining exposed to the solvent. The palmitoyl chain moiety
      of the ligand is placed in the interior of the protein and bent in a U-shape.
      This part of the ligand is completely buried within a hydrophobic pocket of the
      protein. CONCLUSIONS: . A comparison of the structures of bLTP in the free and
      bound forms suggests that bLTP can accommodate long olefinic ligands by expansion
      of the hydrophobic binding site. This expansion is achieved by a bend of one
      helix, HA, and by conformational changes in both the C terminus and helix HC.
      This mode of binding is different from that seen in the structure of maize nsLTP
      in complex with palmitic acid, where binding of the ligand is not associated with
      structural changes.

PMID- 9032085
TI  - The mystery of diabetes and atherosclerosis: time for a new plot.
AB  - Most patients with diabetes die from macrovascular complications. Little is known
      about the pathogenesis of diabetic vascular disease, but recent advances in
      molecular genetics and oxidation chemistry provide clues to the mystery of
      diabetes and atherosclerosis. Genetic variants of well-known proteins such as
      lipoprotein lipase and apolipoprotein E are common. These proteins are suitable
      candidates for mediating diabetic vascular risk because their variants can
      produce hypertriglyceridemia, a risk factor for atherosclerosis in diabetes.
      However, mutations could have different effects on lipoprotein flux across
      arteries depending on whether expression is dominant in the vascular space or the
      vascular wall. Lipoproteins retained in the arterial wall are subject to
      oxidative modification, which could be dependent on glycoxidation, the enzyme
      myeloperoxidase, or reactive nitrogen species derived from nitric oxide.
      Accelerated vascular disease in diabetes is likely the result of complex
      interactions between metabolic derangements such as hyperglycemia, mutations in
      genes controlling lipid metabolism, and antioxidant defense mechanisms.

PMID- 9032087
TI  - Depot- and sex-specific differences in human leptin mRNA expression: implications
      for the control of regional fat distribution.
AB  - Obese subjects with excess intra-abdominal fat deposition suffer greater adverse
      metabolic consequences than do similarly overweight subjects with a predominantly
      subcutaneous distribution of adiposity. Little is known about the factors
      regulating the regional distribution of body fat. Leptin is a recently
      characterized protein secreted by adipocytes that appears to provide a long-term
      hormonal feedback signal regulating fat mass. No systematic evaluation of site
      related differences in human adipocyte leptin expression has been reported to
      date. Levels of leptin mRNA were examined by quantitative reverse transcription
      polymerase chain reaction in adipocytes isolated from omental and subcutaneous
      adipose depots of nonobese and mildly obese individuals undergoing elective
      surgery. In all individuals studied (n = 24), leptin mRNA levels were higher in
      subcutaneous than in omental adipocytes (P < 0.0001). In contrast, there were no
      consistent site-specific differences in the expression of glycerol-3-phosphate
      dehydrogenase mRNA. The subcutaneous-to-omental ratio of leptin mRNA expression
      was markedly higher in women (5.5 +/- 1.1-fold) than in men (1.9 +/- 0.2-fold) (P
      < 0.02). A significant relationship between BMI and leptin mRNA expression was
      demonstrable in the subcutaneous adipocytes of women (P < 0.006). Thus, leptin
      mRNA appears to be expressed predominantly by subcutaneous adipocytes,
      particularly in women. These findings suggest a possible role for leptin in the
      control of adipose tissue distribution and mass.

PMID- 9032086
TI  - Interactions between leptin and hypothalamic neuropeptide Y neurons in the
      control of food intake and energy homeostasis in the rat.
AB  - Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease
      body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate
      nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial
      nuclei (DMH) are postulated to control energy balance by stimulating feeding and
      inhibiting thermogenesis, especially under conditions of energy deficit. We
      investigated whether leptin's short-term effects on energy balance are mediated
      by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected
      into the lateral ventricle of fasted adult Wistar rats inhibited food intake by
      20-25% between 2 and 6 h after administration, compared with saline-treated
      controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT)
      rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations
      by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased
      hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P
      < 0.01). A second study examined changes in leptin during 5 days'
      intracerebroventricular NPY administration (10 microg/day), which induced
      sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA
      levels in epididymal fat were comparable to those in saline-treated controls
      (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin
      levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P <
      0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels
      in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's
      hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in
      raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN
      neurons may interact in a homeostatic loop to regulate body fat mass and energy
      balance.

PMID- 9032088
TI  - Improved insulin sensitivity by bezafibrate in rats: relationship to fatty acid
      composition of skeletal-muscle triglycerides.
AB  - We investigated the effect of the lipid-lowering agent, bezafibrate, on insulin
      sensitivity in a dietary model of insulin resistance. Male Sprague-Dawley rats
      were divided into four groups: control group, administered a standard diet; high
      fructose group, given a 40% fructose diet; high-fructose plus lard group, given a
      40% fructose diet with 7% lard; and bezafibrate group, given a 40% fructose plus
      7% lard diet with 10 mg x kg-1 x day-1 of oral bezafibrate. Insulin action was
      assessed after 2 weeks with a steady-state plasma glucose (SSPG) level. The fatty
      acid (FA) composition of skeletal-muscle triglycerides was also determined. A
      higher SSPG level (20.9 +/- 0.9 vs. 16.5 +/- 1.1 mmol/l in the control group, P <
      0.05) as well as a higher systolic blood pressure (120 +/- 2 vs. 101 +/- 2 mmHg,
      P < 0.01) was observed in the high-fructose plus lard group, but not in the high
      fructose group. These changes were prevented by bezafibrate administration. The
      FA composition of skeletal-muscle triglycerides demonstrated a higher percentage
      of saturated and monounsaturated FAs (P < 0.01) and a lower percentage of
      polyunsaturated FAs (P <0.01) in the high-fructose plus lard group versus the
      control group. These changes were consistent with differences in the dietary
      intake of FAs. Bezafibrate virtually normalized the FA composition in the high
      fructose plus lard group. The ratio of C20:4 to C20:3, an index of delta5
      desaturase activity, was significantly higher in the bezafibrate group versus the
      high-fructose plus lard group (8.60 +/- 0.76 vs. 2.04 +/- 0.27, P < 0.01). In
      conclusion, the dietary FA composition was closely related to insulin resistance
      in rats fed 40% fructose. Bezafibrate increased delta5 desaturase activity. Such
      action may contribute to the improvement of insulin sensitivity.

PMID- 9032089
TI  - Cell-specific regulation of IRS-1 gene expression: role of E box and C/EBP
      binding site in HepG2 cells and CHO cells.
AB  - Insulin receptor substrate 1 (IRS-1) is one of the major substrates of insulin
      receptor tyrosine kinase and mediates multiple insulin signals downstream. We
      have previously shown that the levels of IRS-1 mRNA varied in different tissues.
      To elucidate the molecular mechanisms of the tissue specific regulation of IRS-1,
      we have studied the cis-acting elements and transacting factors in CHO and HepG2
      cells. Using the chloramphenicol acetyltransferase (CAT) assay with the various
      deletion mutants of the IRS-1 promoter-CAT fusion plasmids, several regions
      responsible for positive or negative regulation in each cell line were
      identified. A region from -1645 to -1585 bp, which regulated expression
      negatively in CHO cells and positively in HepG2 cells, was further analyzed.
      Within this region a fragment from -1645 to -1605 bp upregulated the IRS-1
      promoter only in HepG2 cells, whereas a fragment from -1605 to -1585 bp
      downregulated only in CHO cells. In the gel mobility shift assay, several nuclear
      proteins that bind to these fragments were detected, and among them, two nuclear
      proteins that bind to a potential E box (nucleotide [nt] -1635 to -1630) and two
      nuclear proteins that bind to a potential C/EBP binding site (nt -1599 to -1591)
      were identified in HepG2 and CHO cells, respectively. CAT assays using promoters
      mutated at the E box or at the C/EBP binding site revealed that these sequences
      were responsible for cell-specific regulation of the IRS-1 gene. We therefore
      concluded that the two nuclear proteins that bind to the E box regulate IRS-1
      gene expression positively in HepG2 cells and the two nuclear proteins that bind
      to the C/EBP binding site regulate it negatively in CHO cells.

PMID- 9032090
TI  - New monoclonal antibody diagnostic reagents for type I diabetes: differential
      lymphocyte surface antigen expression related to disease.
AB  - New cellular-based reagents are needed to diagnose type I diabetes as well as to
      monitor the outcomes of clinical trials at early time points. Four new monoclonal
      antibodies (mAbs) have been shown to demonstrate reduced binding to lymphocytes
      from identical twins with long-term type I diabetes relative to that observed
      with lymphocytes from their twin partners without diabetes or from control
      subjects. Biochemical analysis revealed mAb 3G12EG recognized an unidentified 45
      kDa protein, whereas mAb 2E8F1 and 5B6E11 did not appear to precipitate specific
      proteins as detected by SDS-PAGE. Electrophoresis under reducing and nonreducing
      conditions and peptide mapping revealed that mAb 8F410 recognizes a novel dimeric
      form of HLA class I molecule. Predictions from crystallography studies suggested
      previously this class I dimer as the optimal activation of a single CD8 T-cell.
      In B-cells from both normal and diabetic individuals, the class I dimer was
      minimally associated with beta2-microglobulin rapidly formed in the endoplasmic
      reticulum. These new reagents appear to be able to identify new lymphocyte
      surface phenotypes associated with diabetes expression in both fresh blood
      samples and Epstein-Barr virus-established cell lines.

PMID- 9032092
TI  - MHC class II-dependent abnormal reactivity toward bacterial superantigens in
      immune cells of NOD mice.
AB  - Superantigens have been implicated in the pathogenesis of type I diabetes and
      other immune-mediated diseases. We therefore tested the hypothesis of an abnormal
      reactivity of the immune system toward bacterial superantigens during the
      prediabetic phase. For this purpose, splenocytes from NOD (H-2g7) mice were
      exposed to two well-characterized superantigens: Staphylococcal aureus
      enterotoxin-B (SEB) and toxic shock syndrome toxin-1 (TSST-1). Cells from BALB/c
      (H-2d) and C57BL/6 (H-2b) mice as well as those from NON (H-2non) and NOR (H-2g7)
      mice were used as controls. After 72 h of co-culture with the superantigens or
      the mitogen concanavalin A (Con A), proliferative response and mitochondrial
      activity were determined. In the culture supernatants, the cytokines gamma
      interferon (IFN-gamma) and interleukin 10 (IL-10) were measured. Striking
      similarities between NOD cells and major histocompatiblity complex (MHC)
      identical NOR cells could be observed with regard to a low proliferative and
      mitochondrial response to SEB, accompanied by a normal response to TSST-1 and Con
      A, respectively. In addition, only NOD and NOR spleen cells were low producers of
      the T-helper 1 (Th1) cytokine IFN-gamma in response to SEB. Conversely,
      abnormally high IFN-gamma levels were induced by TSST-1 in NOD and NOR spleen
      cells. The cytokine response to Con A was also biased toward IFN-gamma in both
      NOD and NOR. Since IFN-gamma and IL-10 are crucial disease-promoting or 
      protecting mediators in prediabetic NOD mice, superantigens may affect
      pathogenesis by acting on the Th1/Th2 cytokine balance. The low responder status
      toward SEB in NOD spleen cells may be of pathogenetic relevance in view of recent
      findings that the insulin B-chain also interacts with the SEB binding site on MHC
      class II molecules. In conclusion, we show here that immune cells from mice with
      a diabetes-associated MHC type respond differently to common environmental
      superantigens than do immune cells from control strains.

PMID- 9032091
TI  - Insulin resistance prevented by portal delivery of insulin in rats with renal
      subcapsular islet grafts.
AB  - We determined the metabolic effects of insulin derived from renal subcapsular
      islet grafts, either with systemic delivery of insulin through renal venous
      drainage (REN) or with portal delivery of insulin after renal vein-to-superior
      mesenteric vein anastomosis (RMA), in streptozotocin-induced diabetic Lewis rats,
      in comparison with normal rats. After gavage glucose, the plasma glucose
      responses were similar to normal in REN and RMA rats; however, hyperinsulinemia
      occurred in REN rats (area under the concentration curves [AUCs] of insulin, 27
      +/- 3 nmol x 1(-l) min) in comparison with RMA (14 +/- 2) and normal rats (19 +/-
      2), P < 0.003, with no difference in C-peptide responses. The ratio of AUC C
      peptide to AUC insulin was lower in REN (2.0 +/- 0.2) than in RMA (3.4 +/- 0.3)
      and normal animals (3.2 +/- 0.3), P < 0.0005. In euglycemic-hyperinsulinemic
      clamp studies using the same insulin infusion rate (10 pmol x kg(-1) x min(-1),
      insulin resistance was found in REN animals (mean glucose infusion rate [GIR],
      REN: 7.5 +/- 1.2; RMA: 12.0 +/- 1.2; normal: 12.7 +/- 1.0 mg x kg(-1) x min(-1);
      P < 0.008), with higher steady-state insulin levels in REN (554 +/- 63 pmol/l)
      than in RMA (291 +/- 26) and normal rats (269 +/- 60), P < 0.0001. With matching
      steady-state insulin levels in RMA and REN rats during infusion of insulin at 20
      pmol x kg(-1) x min(-1) in RMA rats (steady-state insulin 623 +/- 64 pmol/l), GIR
      was 15.7 +/- 0.7 mg x kg(-1) x min(-1). Thus, systemic delivery of insulin from
      islet grafts is associated with hyperinsulinemia, insulin resistance, and
      decreased metabolic clearance of insulin. These abnormalities are prevented by
      portal delivery of insulin from islet grafts in the same site. The findings are
      consistent with the hypothesis that portal delivery of insulin is important in
      maintenance of normal whole-body insulin sensitivity.

PMID- 9032093
TI  - Mapping novel pancreatic islet genes to human chromosomes.
AB  - A strategy was developed to generate expressed sequence tags (ESTs) from human
      pancreatic islet gene products using differential display of mRNA. Screening of
      over 2,000 cDNA amplification products identified 42 cDNAs that were
      preferentially expressed in pancreatic islets relative to exocrine tissue. Public
      database analysis showed that 29 (69%) corresponded to novel genes, in contrast
      with only 66 of 250 (26.4%) cDNA clones randomly selected from a human islet
      library. Reverse transcription-polymerase chain reaction (RT-PCR) and/or Northern
      analysis of RNA from multiple tissues confirmed that expression was enhanced in
      human islet cell RNA for 11 of 15 tested cDNAs. Sequence-tagged sites developed
      from 19 islet cDNAs were used to map these genes to human chromosomes using a
      combination of monochromosomal somatic-cell hybrids, genome-wide radiation
      hybrids, and mega-yeast artificial chromosome analysis. These results indicate
      that this PCR-based cDNA selection strategy yields information on a distinct
      subset of pancreatic islet transcribed sequences, which complements ongoing human
      EST identification efforts based on random cDNA selection. These mapped ESTs may
      be used to assist in the positional cloning of diabetes susceptibility genes.

PMID- 9032094
TI  - Long-chain fatty acids inhibit acetyl-CoA carboxylase gene expression in the
      pancreatic beta-cell line INS-1.
AB  - The mechanism whereby long-term exposure of the beta-cell to fatty acids alters
      the beta-cell response to glucose is not known. We hypothesized that fatty acids
      may alter beta-cell function by changing the expression level of metabolic
      enzymes implicated in the regulation of insulin secretion, in particular acetyl
      CoA carboxylase (ACC). This enzyme catalyzes the formation of malonyl-CoA, a key
      regulator of fatty acid oxidation. Using the beta-cell line INS-1 as a model, the
      results show that the polyunsaturated fatty acid linoleate (C18:2) inhibited both
      basal and glucose-stimulated ACC mRNA induction. The inhibition was detected by 4
      6 h, and a maximal 60% effect occurred at 12 h after cell exposure to the fatty
      acid. Linoleate, as glucose, did not modify the half-life of the ACC transcript.
      Prolonged exposure of INS-1 cells to linoleate also inhibited ACC protein
      accumulation at low and high glucose. The saturated fatty acids myristate
      (C14:0), palmitate (C16:0), and stearate (C18:0) were also effective as well as
      the monounsaturated oleate (C18:1) and the short-chain fatty acids butyrate
      (C4:0) and caproate (C6:0); long-chain omega3 fatty acids were ineffective. The
      threshold concentration for long-chain fatty acids was 0.05 mmol/l, and maximal
      inhibition occurred at 0.3 mmol/l. 2-bromopalmitate, a nonmetabolizable analog,
      had no effect, suggesting that fatty acids must be metabolized to change ACC gene
      expression. Prolonged exposure of INS-1 cells to palmitate, oleate, and linoleate
      markedly altered the glucose-induced insulin response, resulting in high basal
      insulin release and a suppression of glucose-induced insulin secretion. This was
      associated with an exaggerated (twofold to threefold) rate of fatty acid
      oxidation at all tested glucose concentrations. The data provide a possible
      mechanism to at least partially explain how fatty acids cause beta-cell
      insensitivity to glucose, i.e., by downregulating ACC with a resulting
      exaggerated fatty acid oxidation.

PMID- 9032095
TI  - The alpha2-adrenergic receptor is more effective than the galanin receptor in
      activating G-proteins in RINm5F beta-cell membranes.
AB  - Activated receptors for galanin and norepinephrine, and for several other
      agonists, inhibit insulin release from pancreatic beta-cells via pertussis toxin
      sensitive Gi- and Go-proteins and by acting on at least four cellular mechanisms.
      These mechanisms include repolarization via activation of the ATP-sensitive
      potassium (K ATP) channel, inhibition of adenylyl cyclase, and inhibition by
      unknown mechanism at a "distal" site. For norepinephrine and galanin there is
      also inhibition of the L-type Ca2+ channel. Consequently, during simultaneous
      activation by multiple agonists, the effectiveness with which a receptor
      interacts with the G-proteins will, to some extent, determine the responses. This
      could have important consequences for the beta-cell. Therefore, the G-protein
      interactions of two activated receptors, those for norepinephrine and galanin,
      were compared in the same beta-cell membranes. Measurements were made of the
      rates of receptor-G-protein interaction (by GTPgammaS binding) and of the rates
      of turnover of G-proteins (by GTPase activity). A comparison was also made of the
      ability of norepinephrine and galanin to facilitate ADP ribosylation of the alpha
      subunits of Gi and Go by cholera toxin (CTX). Such CTX-induced ADP ribosylation
      of Gi and Go occurs during G-protein interaction with an activated receptor. By
      measurement of the number of receptors in the membrane preparation used, the
      relative effectiveness of the two receptors was assessed. The alpha2-adrenergic
      receptor was found to be markedly more effective than the galanin receptor in
      activating G-proteins.

PMID- 9032096
TI  - Increased lipogenic capacity of the islets of obese rats: a role in the
      pathogenesis of NIDDM.
AB  - The onset of NIDDM in obese Zucker diabetic fatty (fa/fa) rats is preceded by a
      striking increase in the plasma levels of free fatty acids (FFAs) and by a
      sixfold rise in triglyceride content in the pancreatic islets. The latter finding
      provides clear evidence of elevated tissue levels of long-chain fatty acyl CoA,
      which can impair beta-cell cell function. To determine if the triglyceride
      accumulation is entirely the passive consequence of high plasma FFA levels or if
      prediabetic islets have an increased lipogenic capacity that might predispose to
      NIDDM, the metabolism of long-chain fatty acids was compared in islets of obese
      prediabetic and nonprediabetic Zucker diabetic fatty (ZDF) rats and of lean
      Wistar and lean ZDF rats. When cultured in 1 or 2 mmol/l FFA, islets of both
      female and male obese rats accumulated, respectively, 7 and 15 times as much
      triglyceride as islets from lean rats exposed to identical FFA concentrations.
      The esterification of [14C]palmitate and 9,10-[3H]palmitate was increased in
      islets of male obese rats and could not be accounted for by defective oxidation
      of 9,10-[3H]-palmitate. Glycerol-3-PO4 acyl-transferase (GPAT) activity was 12
      times that of controls. The mRNA of GPAT was increased in islets of obese rats.
      We conclude that, in the presence of comparable elevations in FFA concentrations,
      the islets of obese prediabetic rats have a higher lipogenic capacity than
      controls. This could be a factor in their high risk of diabetes.

PMID- 9032097
TI  - Effects of multiple daily insulin injections and intraperitoneal insulin therapy
      on cholesteryl ester transfer and lipoprotein lipase activities in NIDDM.
AB  - Although the relationship between the actions of cholesteryl ester transfer
      protein (CETP) and atherosclerosis is complex, a strong body of evidence suggests
      that its activity (cholesteryl ester transfer [CET]) is proatherogenic. We have
      previously shown that CET is increased in IDDM patients receiving conventional
      subcutaneous insulin treatment and normalized when systemic insulin levels are
      lowered with intraperitoneal insulin delivery (IP). Since CET has been found by
      many observers to also be accelerated in NIDDM, we sought to determine whether
      the same salutary effect could be achieved in insulin-requiring NIDDM men before
      and 7 months after randomization to an intensive treatment regimen (Rx) of either
      IP (n = 9) or multiple daily insulin injections (MDI; n = 13). HbA1c improved to
      the same degree in both groups (MDI group: 9.4 +/- 1.1% pre-Rx vs. 7.2 +/- 0.7%
      post-Rx [P < 0.001]; IP group: 9.2 +/- 1.3% pre-Rx vs. 7.1 +/- 0.5% post-Rx [P <
      0.001]). Compared with pre-Rx levels, plasma triglycerides were not significantly
      changed by either treatment (MDI group: 136 +/- 80 mg/dl pre-Rx vs. 139 +/- 87
      mg/dl post-Rx; IP group: 157 +/- 63 mg/dl pre-Rx vs. 188 +/- 89 mg/dl post-Rx),
      though an upward trend followed IP. Before randomization, CET estimated with both
      mass and isotopic assays was greater in the NIDDM subjects than in nondiabetic
      control subjects (P < 0.001). With improved glycemic control, CE mass transfer
      declined in both groups, but only reached normal levels in the IP group (MDI
      group at 2 h: 49.0 +/- 13.7 [mean +/- SD] pg pre-Rx vs. 29.5 +/- 15.3 microg post
      Rx [-39.7%, P < 0.01]; IP group at 2 h: 40.8 +/- 23.3 microg pre-Rx vs. 10.9 +/-
      6.5 microg post-Rx [-73.2%, P < 0.05]) and remained abnormally increased (P <
      0.005) in the subjects receiving MDI. Total lipolytic activity after intensive
      treatment was unchanged from pretreatment levels, which were similar to those of
      the reference group. Although directional changes in lipoprotein lipase (LpL) and
      hepatic triglyceride lipase (HTGL) similar to those found in IDDM after MDI and
      IP were observed, they were not statistically significant. Thus, while improved
      glycemic control alone achieved by either MDI or IP reduced the pathological
      increase in CET in these insulin-treated NIDDM men, normalization was only
      achieved in those treated with IP. Despite near-normal HbA1c levels, CET remained
      abnormally increased in NIDDM patients treated rigorously with conventional
      subcutaneous insulin delivery.

PMID- 9032098
TI  - Impaired basal glucose effectiveness in NIDDM: contribution of defects in glucose
      disappearance and production, measured using an optimized minimal model
      independent protocol.
AB  - People with NIDDM are resistant to insulin. The present studies sought to
      determine whether the ability of glucose to regulate its own metabolism in the
      presence of basal insulin concentrations is impaired. To address this question,
      basal insulin concentrations were maintained constant with an exogenous insulin
      infusion, while endogenous hormone secretion was inhibited by somatostatin. The
      integrated glycemic response above baseline during identical prandial glucose
      infusions was greater (1,411 +/- 94 vs. 938 +/- 45 mmol/l per 5 h; P < 0.01) in
      the diabetic subjects than in the nondiabetic subjects, indicating a decrease in
      net glucose effectiveness. [6-3H]glucose also was infused to determine whether
      the decrease in net glucose effectiveness was due to a decrease in the ability of
      glucose to stimulate its own uptake and/or to suppress its own production.
      Despite identical rates of tracer infusion, the increment in plasma concentration
      of [6-3H]glucose was higher (4.50 +/- 0.29 vs. 3.16 +/- 0.21 x 10(5) dpm/ml per 5
      h; P < 0.05) in the diabetic subjects than in the nondiabetic subjects. This was
      due to both a decrease (P < 0.05) in the ability of glucose to stimulate its own
      disappearance via mass action and to a greater (P < 0.01) inhibitory effect of
      glucose on its own clearance. The increase in glucose concentration resulted in
      prompt and comparable suppression of endogenous glucose production in both
      groups. Under these optimized conditions, indexes of glucose effectiveness
      calculated with both the "cold" and "hot" minimal models also were lower (P <
      0.05) in the diabetic subjects than in the nondiabetic subjects and were highly
      correlated (r = 0.94-0.99; P < 0.001) with the indexes of glucose effectiveness
      calculated from the increments above baseline of glucose and [6-3H]glucose
      concentration. We conclude that the ability of glucose to regulate its own
      metabolism in the presence of basal insulin concentrations is abnormal in people
      with NIDDM.

PMID- 9032099
TI  - Cardiac and glycemic benefits of troglitazone treatment in NIDDM. The
      Troglitazone Study Group.
AB  - Troglitazone is a thiazolidinedione under development for the treatment of NIDDM
      and potentially other insulin-resistant disease states. Treatment with
      troglitazone is associated with an improvement in hyperglycemia,
      hyperinsulinemia, and insulin-mediated glucose disposal. No significant side
      effects have been observed in humans. Because of reported cardiac changes in
      animals treated with drugs of this class, this multicenter 48-week study was
      conducted to evaluate whether NIDDM patients treated with troglitazone develop
      any cardiac mass increase or functional impairment. A total of 154 NIDDM patients
      were randomized to receive troglitazone 800 mg q.d. or glyburide titrated to
      achieve glycemic control (< or =20 mg b.i.d. or q.d.). Two-dimensional
      echocardiography and pulsed Doppler were used to measure left ventricular mass
      index (LVMI), cardiac index (CI), and stroke volume index (SVI). All
      echocardiograms were performed at each center (baseline, 12, 24, 36, and 48
      weeks), recorded on videotape, and forwarded to a blinded central
      echocardiographic interpreter for analysis. The results showed that LVMI of
      patients treated with troglitazone was not statistically or clinically different
      from baseline after 24 or 48 weeks. Statistically significant increases in SVI
      and CI and a statistically significant decrease in diastolic pressure and
      estimated peripheral resistance were observed in troglitazone-treated patients.
      These results were not sex-specific. Glycemic benefits of troglitazone treatment
      were observed as evidenced by long-term improvement of HbA1c and C-peptide
      levels. Furthermore, triglycerides were significantly lower, and HDL was
      significantly higher at weeks 24 and 48. In conclusion, NIDDM patients treated
      with troglitazone do not show any cardiac mass increase or cardiac function
      impairment. Conversely, patients on troglitazone benefited from enhanced cardiac
      output and stroke volume, possibly as a result of decreased peripheral
      resistance. Treatment with troglitazone appears to have a favorable impact on
      known cardiovascular risk factors and could potentially lower cardiovascular
      morbidity in NIDDM patients.

PMID- 9032100
TI  - Insulin lispro in CSII: results of a double-blind crossover study.
AB  - Insulin lispro is a human insulin analog that dissociates more rapidly than human
      regular insulin after subcutaneous injection, resulting in higher insulin levels
      at an earlier point in time and a shorter duration of action. The aim of the
      study was to evaluate if this pharmacokinetic difference would translate into
      better postprandial and overall control in 30 IDDM patients (age, 35.1 +/- 1.5
      years; male-female ratio, 17:13; BMI, 24.8 +/- 0.5 kg/m2; HbA1c, 8.03 +/- 0.13%
      at baseline) treated with continuous subcutaneous insulin infusion (CSII;
      Disetronic H-TRON V100) in a double-blind crossover clinical study. Patients were
      randomized to insulin lispro or human regular insulin for 3 months before
      crossing over to the other insulin for another 3 months. All meal boluses were
      given immediately before breakfast, lunch, and supper. An eight-point blood
      glucose profile was measured once weekly, and HbA1c levels were measured monthly.
      At the end of the 3-month treatment period, HbA1c levels were significantly lower
      with insulin lispro, compared with human regular insulin: 7.66 +/- 0.13 vs. 8.00
      +/- 0.16% (P = 0.0041). While preprandial, bedtime, and 2:00 A.M. values for
      blood glucose were not significantly different, 1-h postprandial blood glucose
      was significantly improved after breakfast, lunch, and dinner with insulin
      lispro, compared with human regular insulin: 8.35 vs. 9.79 mmol/l (P = 0.006),
      7.58 vs. 8.74 mmol/l (P = 0.049), and 7.85 vs. 9.01 mmol/l (P = 0.03). The
      incidence of hypoglycemia per 30 days (blood glucose levels, <3.0 mmol/l) was 8.4
      +/- 1.3 before randomization, decreasing to 6.0 +/- 0.9 for insulin lispro and to
      7.6 +/- 1.3 for regular insulin during the last month of the study. Two patients
      in each group reported insulin precipitation. We conclude that insulin lispro
      improves glycemic control in CSII without increasing the risk of hypoglycemia.

PMID- 9032101
TI  - Muscle Rad expression and human metabolism: potential role of the novel Ras
      related GTPase in energy expenditure and body composition.
AB  - Ras associated with diabetes (Rad), a new ras-related GTPase, was recently
      identified by subtractive cloning as an mRNA in skeletal muscle that is
      overexpressed in NIDDM. To better understand its metabolic significance, we
      measured skeletal muscle Rad expression in well-characterized insulin sensitive
      (IS) and insulin resistant (IR) subjects with normal glucose tolerance and in
      untreated NIDDM patients. We found no differences in expression of Rad mRNA
      levels among IS, IR, and NIDDM groups using a ribonuclease protection assay (0.22
      +/- 0.06, 0.13 +/- 0.01, and 0.16 +/- 0.02 relative units, respectively; NS) and
      no differences in Rad protein expression using a specific anti-peptide Rad
      antibody (1.05 +/- 0.18, 1.14 +/- 0.08, and 1.08 +/- 0.21 units/mg protein,
      respectively; NS). However, Rad protein levels were positively correlated with
      BMI (r = 0.43, P = 0.03) and percentage body fat (r = 0.55, P < 0.005), two
      independent measures of obesity, and negatively correlated with resting metabolic
      rate (r = 0.49, P = 0.01). In multiple regression analyses, percentage body fat
      and resting metabolic rate independently accounted for 30 and 10% of individual
      variability in muscle Rad protein expression. In conclusion, Rad expression in
      skeletal muscle is not altered as a function of insulin resistance or NIDDM in
      humans. However, these data, for the first time, implicate a role for Rad in
      regulating body composition and energy expenditure and provide a framework for
      studies designed to elucidate Rad's cellular functions.

PMID- 9032102
TI  - Differential regulation of the p80 tumor necrosis factor receptor in human
      obesity and insulin resistance.
AB  - Previous studies have shown that tumor necrosis factor (TNF)-alpha production
      from adipose tissue is elevated in rodent and human obesity and plays an
      important role in insulin resistance in experimental animal models. In this
      study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2)
      in human obesity and demonstrated that obese female subjects express
      approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold
      more soluble TNFR2 in circulation relative to lean control subjects. In contrast,
      TNFR1 expression and protein levels were similar in these subjects. TNFR2
      expression levels in adipose tissue were strongly correlated with BMI (r = 0.65,
      P < 0.001) and level of hyperinsulinemia (P < 0.001), an indirect measure of
      insulin resistance, as well as level of TNF-alpha mRNA expression in fat tissue
      (r = 0.56, P < 0.001). These results suggest that TNFR2 might play a role in
      human obesity by modulating the actions of TNF-alpha.

PMID- 9032103
TI  - Visceral fat and race-dependent health risks in obese nondiabetic premenopausal
      women.
AB  - Our previous finding that a waist-to-hip ratio (WHR) >0.85 was not associated
      with similar health risks in black, compared with white, obese premenopausal non
      diabetic women of similar fatness is attributed to either 1) a different
      relationship between WHR and visceral adiposity or 2) differences in the
      relationship between visceral adiposity and the metabolic abnormalities of
      obesity. We measured visceral (VAT) and subcutaneous adipose tissue (SCAT) areas
      at midwaist in 25 black and 25 white obese nondiabetic pre-menopausal women with
      similar BMI, percentage body fat, and wide range of WHR (0.7-0.95 for black women
      and 0.7-0.9 for white women) and then compared insulin sensitivity index (SI),
      glucose and insulin areas under the 2-h curve (AUCs) during an oral glucose
      tolerance test (OGTT), and blood lipids in the two groups before and after
      adjustments for total body and visceral adiposity. After adjusting for total body
      fat mass (FM), obese black women had significantly less VAT (by 32 cm2) and lower
      VAT/SCAT for any given WHR. The regression equations predicting the SI the
      glucose and insulin AUCs, and the triglyceride and HDL cholesterol levels from
      regional adipose tissue measurements (VAT, SCAT, or VAT/SCAT) and from total body
      fat (FM or percentage body fat) had slopes that were not significantly different
      for black and white women. LDL cholesterol levels were independently related to
      VAT in black but not in white women. The black women had a similar SI insulin
      AUC, and triglyceride levels but significantly lower glucose AUC and higher HDL
      cholesterol levels (P < 0.001), after adjusting for VAT and FM. Regression
      analysis of the pooled data showed that high VAT and high VAT/SCAT, but not SCAT,
      predicted lower SI higher glucose and insulin AUCs during OGTT, and higher
      triglyceride levels, independent of total adiposity. We conclude that while
      increases in VAT and VAT/SCAT adversely affect metabolism in both black and white
      obese premenopausal women, similar levels of total body and visceral adiposity
      are associated with different metabolic risk factors in these groups.

PMID- 9032104
TI  - The receptor for advanced glycation end products mediates the chemotaxis of
      rabbit smooth muscle cells.
AB  - Long-term incubation of proteins with glucose leads to advanced glycation end
      products (AGEs) with fluorescence and a brown color. We recently demonstrated
      immunologically the intracellular AGE accumulation in smooth muscle cell (SMC)
      derived foam cells in advanced atherosclerotic lesions. To understand the
      mechanism of AGE accumulation in these foam cells, we have now characterized the
      interaction of AGE proteins with rabbit-cultured arterial SMCs. In experiments at
      4 degrees C, 125I-labeled AGE-bovine serum albumin (AGE-BSA) showed a dose
      dependent saturable binding to SMCs with an apparent dissociation constant (Kd)
      of 4.0 microg/ml. In experiments at 37 degrees C, AGE-BSA underwent receptor
      mediated endocytosis and subsequent lysosomal degradation. The endocytic uptake
      of 125I-AGE-BSA was effectively inhibited by unlabeled AGE proteins such as AGE
      BSA and AGE-hemoglobin, but not by acetylated LDL and oxidized LDL, well-known
      ligands for the macrophage scavenger receptor (MSR). Moreover, the binding of
      125I-AGE-BSA to SMCs was affected neither by amphoterin, a ligand for one type of
      the AGE receptor, named RAGE, nor by 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole
      hexanoic acid-BSA, a ligand for the other AGE receptors, p60 and p90. This
      indicates that the endocytic uptake of AGE proteins by SMCs is mediated by an AGE
      receptor distinct from MSR, RAGE, p60, and p90. To examine the functional role of
      this AGE receptor, the migratory effects of AGE-BSA on these SMCs were tested.
      Incubation with 1-50 microg/ml of AGE-BSA for 14 h resulted in significant dose
      dependent cell migration. The AGE-BSA-induced SMC migration was chemotactic in
      nature and was significantly inhibited (approximately 80%) by an antibody against
      transforming growth factor-beta (TGF-beta), and the amount of TGF-beta secreted
      into the culture medium from SMC by AGE-BSA was sevenfold higher than that of
      control, indicating that TGF-beta is involved in the AGE-induced SMC chemotaxis.
      These data suggest that AGE may play a role in SMC migration in advanced
      atherosclerotic lesions.

PMID- 9032105
TI  - Expression of transforming growth factor-beta and type IV collagen in early
      streptozotocin-induced diabetes.
AB  - The earliest manifestations of type I diabetic nephropathy include mesangial
      matrix expansion, basement membrane thickening, and renal hypertrophy.
      Transforming growth factor (TGF)-beta, a potent inducer of matrix protein
      synthesis, is a prime candidate to mediate the glomerular changes observed in
      diabetes. However, the temporal expression of TGF-beta and matrix proteins during
      the early stage of diabetic nephropathy has not been clearly defined. Using in
      situ hybridization and immunohistochemistry, we determined the expression of TGF
      beta and type IV collagen mRNAs and proteins in glomeruli and interstitium of
      diabetic rats 3, 7, and 14 days after streptozotocin (STZ) administration. There
      was a marked increase in the expression of TGF-beta and alpha1(IV) procollagen
      mRNAs in glomerular and tubulointerstitial cells as early as 3 days after
      induction of diabetes, an effect that persisted for 14 days. A concomitant
      increase in TGF-beta and type IV collagen proteins was also observed at each time
      point. Insulin treatment substantially inhibited the increased expression of TGF
      beta and collagen type IV mRNAs and proteins. We conclude that TGF-beta is
      increased in glomeruli during the early phase of rapid renal growth in diabetes.
      These findings suggest that TGF-beta may be a key factor involved in the
      pathogenesis of basement membrane thickening and extracellular matrix
      accumulation. Inhibition of TGF-beta and type IV collagen expression by insulin
      treatment suggests that they may be useful structural markers for determining the
      efficacy of therapeutic intervention during early diabetic nephropathy.

PMID- 9032106
TI  - Differences between nisoldipine and lisinopril on glomerular filtration rates and
      albuminuria in hypertensive IDDM patients with diabetic nephropathy during the
      first year of treatment.
AB  - Our objective was to compare the effect of a long-acting calcium antagonist
      (nisoldipine) versus an ACE inhibitor (lisinopril) on albuminuria, arterial blood
      pressure, and glomerular filtration rate (GFR) in hypertensive IDDM patients with
      diabetic nephropathy. We performed a 1-year, double-blind, double-dummy,
      randomized, controlled study comparing nisoldipine (20-40 mg once daily) with
      lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic
      nephropathy. Three patients dropped out, and results for the remaining 49 (25
      nisoldipine, 24 lisinopril) are presented. Diuretics were required in 10
      nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory
      blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples
      (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded
      every 6 months. Mean arterial blood pressure (24 h) was reduced from (mean +/-
      SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the
      lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P =
      0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21
      65) in the lisinopril group versus an increase of 11% (-3 to 27) in the
      nisoldipine group (P = 0.001). Fractional albumin clearance was reduced 37% (95%
      CI 4-59%) in the lisinopril versus an increase of 35% (8-69%) in the nisoldipine
      group (P < 0.01). GFR decreased from 85 +/- 5 ml x min(-1) x 1.73 m(-2) to 73 +/-
      5 in the lisinopril group and from 84 +/- 6 to 80 +/- 7 in the nisoldipine group
      (P < 0.05). The effect of study medication on albuminuria and GFR was independent
      of changes in systemic blood pressure and baseline variables in multiple
      regression analyses. In summary, lisinopril reduced albuminuria, but also GFR, to
      a greater extent than did nisoldipine in hypertensive IDDM patients with diabetic
      nephropathy during the 1st year of treatment. Longer follow-up is required to
      clarify whether these drugs have different renoprotective effects.

PMID- 9032107
TI  - Phosphorylation of myosin light chain in resting platelets from NIDDM patients is
      enhanced: correlation with spontaneous aggregation.
AB  - Platelet function in patients with NIDDM is enhanced. We have found that
      spontaneous aggregation (i.e., the formation of small-sized aggregates in the
      absence of agonist stimulation) occurs at a high rate in platelets from NIDDM
      patients. We then investigated basal myosin light chain 20 (MLC) phosphorylation,
      which plays a key role in platelet shape change and aggregation, using a
      monoclonal antibody against a phosphorylation site (serine 19 residue) in the MLC
      molecule in platelets from these patients. Standard calibration curves obtained
      from purified MLC or the phosphorylated form of myosin light chain 20 (MLC-P)
      were linear within the range of 0-150 ng for MLC and 0-3 ng for MLC-P. The amount
      of MLC or MLC-P in platelets was estimated, and basal MLC phosphorylation was
      calculated. Platelets were obtained from 9 young healthy control subjects, 13 age
      and sex-matched nondiabetic control subjects, and 13 patients with NIDDM. The
      basal MLC phosphorylation in platelets was significantly higher in the NIDDM
      patients than in the control subjects, irrespective of age. These findings
      suggest that platelets from NIDDM patients are activated in vivo. Platelets
      obtained from NIDDM patients generated spontaneous aggregation, the degree of
      which was significantly higher than that in control subjects. Platelet
      spontaneous aggregation correlated well with basal MLC phosphorylation. These
      findings suggest that increases in basal MLC in platelets may be one factor
      leading to hyperaggregability of platelets in these patients.

PMID- 9032108
TI  - Identification of a common amino acid polymorphism in the p85alpha regulatory
      subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance
      constant, glucose effectiveness, and the insulin sensitivity index.
AB  - Phosphatidylinositol 3-kinase (PI3-K) may regulate the basal plasma membrane
      glucose transporter recycling and the organization of the transporter
      intracellular pool in addition to being an insulin signal for translocation of
      glucose transporters to the plasma membrane. The objectives of the present study
      were to examine for genetic variability in the human regulatory p85alpha subunit
      of PI3-K, to look for an association between gene variants and NIDDM in a case
      control study, and to relate identified variability to potential changes in whole
      body insulin sensitivity and glucose turnover in a phenotype study. Single-strand
      conformational polymorphism and heteroduplex analysis of the coding region of the
      regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70
      insulin-resistant NIDDM patients and 12 control subjects revealed three silent
      polymorphisms and a missense mutation at nucleotide position 1020 (G-->A),
      changing a Met to Ile at codon 326. Using allele-specific oligohybridization, we
      found a similar allelic frequency of the codon 326Met-->Ile variant in 404 NIDDM
      patients (0.15 [95% CI 0.13-0.17]) and 224 matched glucose tolerant control
      subjects (0.16 [0.13-0.19]). In a random sample of 380 unrelated healthy young
      Caucasians aged 18-32 years, in whom we have performed a tolbutamide modified
      intravenous glucose tolerance test, we identified 263 wildtype subjects, 109
      heterozygous subjects, and 8 subjects homozygous for the codon 326 variant
      (allelic frequency = 0.16 [0.13-0.19]). No difference in glucose disappearance
      constant (KG), insulin sensitivity index (SI), and glucose effectiveness (SG) was
      observed between wildtype and heterozygous subjects. However, compared with the
      combined values for wildtype and heterozygous carriers, KG was reduced by 40% (P
      = 0.004) and SG by 23% (P = 0.03) in homozygous carriers of the p85alpha variant.
      Moreover, in homozygous carriers, a 32% reduction was found in SI (P = 0.08). In
      conclusion, a codon 326Met-->Ile variant in the gene encoding the PI3-K p85alpha
      regulatory subunit is found in 31% of a random sample of young healthy
      Caucasians. About 2% of the subjects in this population carry the gene variant in
      its homozygous form, and these carriers are characterized by significant
      reductions in whole-body glucose effectiveness and intravenous glucose
      disappearance constant. In itself, the gene variant does not confer an increased
      risk of diabetes.

PMID- 9032109
TI  - Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+
      channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients
      with NIDDM.
AB  - Signals derived from the metabolism of glucose in pancreatic beta-cells lead to
      insulin secretion via the closure of ATP-sensitive K+ channels (KATP). The
      cloning of the gene encoding the beta-cell inward rectifier Kir6.2 (Bir), a
      subunit of the beta-cell KATP channel, provided the opportunity to look for
      mutations in this gene that might contribute to the impaired insulin secretion of
      NIDDM. By single-strand conformational polymorphism (SSCP) analysis on 35
      Northern-European Caucasian patients with NIDDM, six sequence variants were
      detected: Glu10gag-->Lys10aag (E1OK), Glu23gag-->Lys23aag (E23K), Leu270ctg-
      >Val270gtg (L270V), Ile337atc-->Val337gtc (I337V), and two silent mutations.
      Allelic frequencies for the missense variants were compared between the NIDDM
      group (n = 306) and nondiabetic control subjects (n = 175) and did not differ
      between the two groups. Pairwise allelic associations indicated significant
      linkage disequilibrium between the variants in Kir6.2 and between them and a
      nearby pancreatic beta-cell sulfonylurea receptor (SUR1) missense variant
      (S1370A), but these linkage disequilibria did not differ between the NIDDM and
      control groups. The results of these studies thus revealed that mutations in the
      coding region of Kir6.2 1) were not responsible for the previously noted
      association of the SUR1 variants with NIDDM (Inoue H et al., Diabetes 45:825-831,
      1996) and 2) did not contribute to the impaired insulin secretion characteristic
      of NIDDM in Caucasian patients.

PMID- 9032110
TI  - Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their
      relationships to glucose- and tolbutamide-induced insulin secretion, the insulin
      sensitivity index, and NIDDM.
AB  - Kir6.2 is an inwardly rectifying potassium channel that is expressed in
      pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with
      the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and
      also ATP-sensitive potassium channel resembling the native beta-cell channel. The
      objective of this study was to search for mutations in the Kir6.2 gene that might
      be associated with NIDDM or related to altered insulin secretion, insulin action,
      or glucose metabolism in healthy subjects. Using polymerase chain reaction-single
      strand conformation polymorphism analysis (PCR-SSCP) on genomic DNA from 69
      Danish NIDDM patients and 66 matched control subjects, we report the finding of
      three missense polymorphisms in otherwise conserved codons and three silent
      polymorphisms in the gene encoding Kir6.2: codon 23 (GAG/AAG), Glu-->Lys; codon
      190 (GCT/GCC), Ala-->Ala; codon 267 (CTC/CTG), Leu-->Leu; codon 270 (CTG/GTG),
      Leu-->Val; codon 337 (ATC/GTC), Ile-->Val; codon 381 (AAG/AAA), Lys-->Lys. The
      codon 23 and codon 337 amino acid polymorphisms were always coupled. The allelic
      frequencies of the polymorphisms were similar in NIDDM patients and control
      subjects. The amino acid polymorphisms were not associated with altered insulin
      secretion after intravenous glucose or tolbutamide injections or with altered
      glucose effectiveness in a phenotype study of 346 young healthy subjects.
      However, carriers of the maximal load of amino acid variants, the compound
      homozygous codon 23/337 and heterozygous codon 270, had on average a 62% higher
      insulin sensitivity index (P = 0.006), compared with noncarriers. We conclude
      that a combination of common Kir6.2 amino acid variants may contribute to the
      genetic background behind the large variation of the insulin sensitivity index in
      the general population.

PMID- 9032111
TI  - Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the
      extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma
      to-CSF transport of leptin in both the Zucker and Koletsky obese rat.
AB  - The obese phenotypes of the diabetes (db) mouse and fatty fa) rat are due to
      functional null mutations of the leptin receptor (Lepr). The recessive mutation
      in the Koletsky (f) obese rat maps to the same genetic intervals as db and fa and
      fails to complement the fa mutation. Comparison of the sequence of brain Lepr
      cDNA from +/+ and f/f animals reveals a T2349A transversion resulting in a
      Tyr763Stop nonsense mutation in the gene just before the transmembrane domain.
      Virtual absence of Lepr mRNA in whole brain from f/f animals is consistent with
      the presence of a null mutation. The predicted reduced cerebrospinal fluid (CSF)
      transport of leptin in both f/f and fa/fa mutants is reflected in the
      approximately 10-fold lower ratio of CSF/plasma leptin concentration in the obese
      versus lean animals. However, equivalent CSF leptin concentration between lean
      and obese rats (fa/fa, f/f) indicates that leptin can enter the CSF through a non
      Lepr-mediated mechanism, which may be saturated at normal physiological plasma
      leptin concentration.

PMID- 9032112
TI  - Trehalose: a cryoprotectant that enhances recovery and preserves function of
      human pancreatic islets after long-term storage.
AB  - The scarcity of available tissue for transplantation in diabetes and the need for
      multiple donors make it mandatory to use an optimal cryopreservation method that
      allows maximal recovery and preservation of beta-cell function. We have developed
      a method to cryopreserve islets with excellent survival of endocrine cells.
      Current methods use DMSO as cryoprotectant. Our method involves introducing both
      DMSO and the disaccharide trehalose into the cells during cooling. Uptake and
      release of trehalose occurred during the thermotropic lipid-phase transition
      measured in pancreatic endocrine cells between 5 degrees and 9 degrees C, using
      [14C]trehalose. Recovery of adult islets after cryopreservation with 300 mmol/l
      trehalose was 92 vs. 58% using DMSO alone. In vitro function, in terms of insulin
      content and release in response to secretagogues, was indistinguishable from
      fresh islets. Grafts from islets cryopreserved with trehalose contained 14-fold
      more insulin than grafts from islets cryopreserved without trehalose. Results
      with human fetal islet-like cell clusters (ICCs) were more pronounced: recovery
      from cryopreservation was 94%, compared with 42% without trehalose. Complete
      functionality of fetal cells was also restored; tritiated thymidine incorporation
      and insulin content and release were similar to fresh tissue. After
      transplantation in nude mice, there was a 15-fold increase in insulin content of
      grafts from ICCs cryopreserved with trehalose compared with ICCs cryopreserved
      without trehalose. Thus, the addition of trehalose to cryopreservation protocols
      leads to previously unobtainable survival rates of human pancreatic endocrine
      tissue.

PMID- 9032113
TI  - Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase
      activity in skeletal muscle from NIDDM subjects after in vivo insulin
      stimulation.
AB  - We examined the effect of physiological hyperinsulinemia on insulin receptor
      substrate-1 (IRS-1) tyrosine phosphorylation and phosphatidylinositol (PI) 3
      kinase activity in skeletal muscle from six lean-to-moderately obese NIDDM
      patients and six healthy subjects. A rise in serum insulin levels from
      approximately 60 to approximately 650 pmol/l increased IRS-1 tyrosine
      phosphorylation sixfold over basal levels in control muscle (P < 0.01), whereas
      no significant increase was noted in NIDDM muscle. The reduced IRS-1
      phosphorylation in the NIDDM muscle was not related to changes in IRS-1 protein
      content, since IRS-1 protein expression was similar between control and NIDDM
      subjects (16.0 +/- 1.7 vs. 22.9 +/- 4.0 arbitrary units/mg protein for control
      and NIDDM, respectively; NS). Physiological hyperinsulinemia increased PI 3
      kinase activity in control muscle twofold (P < 0.01), whereas no increase in
      insulin-stimulated PI 3-kinase activity was noted in the NIDDM muscle.
      Furthermore, in vitro insulin-stimulated (600 pmol/l) 3-O-methylglucose transport
      was 40% lower in isolated muscle from NIDDM subjects (P < 0.05). The present
      findings couple both reduced insulin-stimulated IRS-1 tyrosine phosphorylation
      and PI 3-kinase activity to the impaired insulin-stimulated glucose transport in
      skeletal muscle from lean-to-moderately obese NIDDM subjects.

PMID- 9032115
TI  - Peroxynitrite causes energy depletion and increases permeability via activation
      of poly (ADP-ribose) synthetase in pulmonary epithelial cells.
AB  - Recent studies show that peroxynitrite is a potent trigger of DNA strand
      breakage, which in turn activates the nuclear repair enzyme poly (ADP-ribose)
      synthetase (PARS), resulting in a cellular energy deficit. Here we present
      evidence that treatment of A549 human pulmonary epithelial cells with
      peroxynitrite (1 mM) results in ADP-ribosylation, NAD+ depletion, inhibition of
      mitochondrial respiration, and increased epithelial paracellular permeability.
      The PARS inhibitor 3-aminobenzamide (1 mM) provided a significant, partial
      protection against the energetic and functional changes. Similarly, inhibition of
      PARS activity by 3-aminobenzamide reduced the peroxynitrite-induced suppression
      of mitochondrial respiration in BEAS-2B human bronchial epithelial cells. Thus,
      PARS activation and energy depletion represents one of the pathways of
      peroxynitrite-mediated epithelial toxicity. Inhibition of PARS may improve
      cellular energy homeostasis in pathophysiologic conditions associated with
      peroxynitrite generation.

PMID- 9032116
TI  - Tumor necrosis factor alpha-mediated host defense against Pneumocystis carinii.

PMID- 9032114
TI  - Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset
      NIDDM: evidence for a mutational hotspot in exon 4.
AB  - We have recently shown that mutations in the gene encoding the transcription
      factor hepatocyte nuclear factor (HNF)-1alpha are the cause of one form of
      maturity-onset diabetes of the young (MODY3). Here, we report the exon-intron
      organization and partial sequence of the human HNF-1alpha gene. In addition, we
      have screened the ten exons and flanking introns of this gene for mutations in a
      group of 25 unrelated white subjects from Germany who presented with NIDDM before
      35 years of age and had a first-degree relative with NIDDM. Mutations were
      identified in nine of these individuals, suggesting that mutations in the HNF
      1alpha gene are a common cause of diabetes in German subjects with early-onset
      NIDDM and a family history of diabetes. Thus, screening for mutations in this
      gene may be indicated in subjects with early-onset NIDDM. Interestingly, three of
      the nine mutations occurred at the same site in exon 4 with insertion of a C in a
      polyC tract, centered around codon 290 (designated Pro291fsinsC), thereby
      resulting in a frameshift during translation and premature termination. Analyses
      of linked DNA polymorphisms in the HNF-1alpha gene indicated that the
      Pro291fsinsC mutation was present on a different haplotype in each subject,
      implying that the polyC tract represents a mutational hot spot. We have also
      identified the mutation in the HNF-1alpha gene in the Jutland pedigree, one of
      the original MODY pedigrees reported in the literature, as being a T-->G
      substitution in codon 241, resulting in the replacement of a conserved Cys by Gly
      (C241G). The information on the sequence of the HNF-1alpha gene and its promoter
      region will facilitate the search for mutations in other subjects and studies of
      the role of the gene in determining normal beta-cell functions.

PMID- 9032117
TI  - Exacerbation of murine Pneumocystis carinii infection by adenoviral-mediated gene
      transfer of a TNF inhibitor.
AB  - The role of mononuclear phagocytes and their cytokine products in host defense
      against Pneumocystis carinii (PC) remains unclear. The cytokine tumor necrosis
      factor (TNF) has been proposed as critical for host defense against this
      pathogen. To investigate the role of this cytokine in PC infection, we treated
      immunocompetent mice (CD4+) or mice depleted of CD4 lymphocytes (CD4-) with a
      recombinant adenovirus encoding a TNF inhibitor gene (AdTNF-R). AdTNF-R treated
      CD4+ animals displayed delayed clearance of PC after intratracheal inoculation,
      whereas AdTNF-R treated CD4 animals developed more severe chronic infection.
      Moreover, AdTNF-R treated CD4- animals, in contrast to control CD4- mice, failed
      to show any interleukin-6 (IL-6) gene induction in the lung after PC challenge.
      The results firmly implicate TNF in host defense against PC, and support a role
      for TNF in orchestrating the intrapulmonary cytokine cascade in PC infection.

PMID- 9032118
TI  - Changes in mononuclear phagocyte microtubules after endotoxin stimulation. I.
      Changes in microtubule stability.
AB  - Microtubules are in a dynamic equilibrium of polymerization and depolymerization.
      In monocytes and macrophages, microtubules bind endotoxin and partly regulate
      inflammatory events such as cytokine production. To characterize the morphologic
      differences between alveolar macrophage and blood monocyte microtubules after LPS
      stimulation, cells were examined by immunofluorescent microscopy and laser
      confocal microscopy. Fresh monocytes contained an average of 26 microtubules per
      cell which significantly increased to 31 microtubules per cell following a 30-min
      exposure to LPS (P < 0.001). Using a nocodazole-based assay of microtubule
      dynamic instability, the half-life of fresh unstimulated human monocyte
      microtubules was approximately 18 s and extended to 26 s following a 30-min
      exposure to LPS. In vitro maturation of monocytes for 18 h increased microtubule
      stability but not number. Compared to monocytes, alveolar macrophage microtubules
      were longer, more numerous, and much more stable. These results suggest that
      alveolar macrophage microtubules are more numerous and stable than blood monocyte
      microtubules and that LPS causes an increase in monocyte microtubule number and
      stability.

PMID- 9032119
TI  - Changes in mononuclear phagocyte microtubules after endotoxin stimulation. II.
      Changes in microtubule composition.
AB  - Microtubules are integral components of the cytoskeleton of human cells and are
      composed of alpha- and beta-tubulin as well as a variable number of microtubule
      associated proteins. In monocytes and macrophages, microtubules bind endotoxin
      and partly regulate endotoxin-induced inflammatory events such as cytokine
      production. Endotoxin causes a rapid alteration in monocyte microtubule
      stability. To characterize the effect of endotoxin on mononuclear phagocyte
      microtubule composition, Western blots and flow cytometry were performed on human
      monocytes and the monocyte/macrophage-like cell line THP-1. Compared to
      unstimulated monocytes, monocytes stimulated with endotoxin for 18 h had
      increased quantities of alpha-, beta-, and tyrosinated alpha-tubulin as well as
      microtubule-associated protein-2. PMA-differentiated THP-1 cells had increased
      levels of alpha-tubulin, beta-tubulin, microtubule-associated protein-5,
      microtubule-associated protein-2, and tau after endotoxin stimulation. These
      results indicate that endotoxin can alter mononuclear phagocyte microtubules by
      causing an increase in certain microtubule component proteins.

PMID- 9032120
TI  - Upregulation of neuropeptides and neuropeptide receptors in a murine model of
      immune inflammation in lung parenchyma.
AB  - The lung is richly supplied with peptidergic nerves that store and secrete
      substance P (SP), vasoactive intestinal peptide (VIP), and other neuropeptides
      known to potently modulate leukocyte function in vitro and airway inflammation in
      vivo. To investigate and characterize neuromodulation of immune responses
      compartmentalized in lung parenchyma, neuropeptide release and expression of
      neuropeptide receptors were studied in lungs of antigen-primed C57BL/6 mice after
      intratracheal challenge with sheep erythrocytes. The concentrations of cytokines
      in bronchoalveolar lavage (BAL) fluid rose early and peaked on day 1 for
      interleukin (IL)-2, interferon gamma, and IL-10; days 1 to 2 for IL-6; and day 3
      for IL-4, whereas the total number and different types of leukocytes in BAL fluid
      peaked subsequently on days 4 to 6 after i.t. antigen challenge. Immunoreactive
      SP and VIP in BAL fluid increased maximally to nanomolar concentrations on days 1
      to 3 and 2 to 7, respectively in lungs undergoing immune responses. The high
      affinity SP receptor (NK-1 R), and VIP types I (VIPR1) and II (VIPR2) receptors
      were localized by immunohistochemistry to surface membranes of mononuclear
      leukocytes and granulocytes in perivascular, peribronchiolar, and alveolar
      inflammatory infiltrates during immune responses. As quantified by reverse
      transcription-polymerase chain reaction, significant increases were observed in
      levels of BAL lymphocyte mRNA encoding NK-1 R (days 2 to 4), VIPR1 (days 2 to 4),
      and VIPR2 (days 4 to 6), and in alveolar macrophage mRNA encoding NK-1 R (days 2
      to 6) and VIPR1 (days 2 to 4), but not VIPR2. Systemic treatment of mice with a
      selective, nonpeptide NK-1 R antagonist reduced significantly the total numbers
      of leukocytes, lymphocytes, and granulocytes retrieved by BAL on day 5 of the
      pulmonary immune response. The results indicate that SP and VIP are secreted
      locally during pulmonary immune responses, and are recognized by leukocytes
      infiltrating lung tissue, and thus their interaction may regulate the recruitment
      and functions of immune cells in lung parenchyma.

PMID- 9032121
TI  - Hemorrhage induces rapid in vivo activation of CREB and NF-kappaB in murine
      intraparenchymal lung mononuclear cells.
AB  - Increased expression of proinflammatory cytokines appears to be an important
      factor contributing to the development of acute lung injury. In murine models,
      mRNA levels of proinflammatory and immunoregulatory cytokines, including IL
      1alpha, IL-1beta, TGF-beta1, and TNF-alpha, are increased in intraparenchymal
      lung mononuclear cells 1 h after hemorrhage. Binding elements for the nuclear
      transcriptional regulatory factors, nuclear factor kappaB (NF-kappaB),
      CCAAT/enhancer binding protein beta (C/EBPbeta), serum protein 1 (Sp1), activator
      protein 1 (AP-1), and the cyclic AMP response-element binding protein (CREB) are
      present in the promoter regions of numerous cytokine genes, including those whose
      expression is increased after blood loss. To investigate early transcriptional
      mechanisms which may be involved in regulating pulmonary cytokine expression
      after hemorrhage, we examined in vivo activation of these five nuclear
      transcriptional factors among intraparenchymal lung mononuclear cells obtained in
      the immediate post-hemorrhage period. Activation of NF-kappaB and CREB, but not
      C/EBPbeta, Sp1, or AP-1, was present in lung mononuclear cells isolated from mice
      15 min after hemorrhage. Inhibition of xanthine oxidase by prior feeding with
      either an allopurinol-supplemented or a tungsten-enriched diet prevented
      hemorrhage-induced activation of CREB, but not NF-kappaB. These results
      demonstrate that hemorrhage leads to rapid in vivo activation in the lung of CREB
      through a xanthine oxidase-dependent mechanism and of NF-kappaB through other
      pathways, and suggest that the activation of these transcriptional factors may
      have an important role in regulating pulmonary cytokine expression and the
      development of acute lung injury after blood loss.

PMID- 9032122
TI  - Pulmonary lymphoid cell activation and cytokine expression in murine AIDS
      associated interstitial pneumonitis.
AB  - Limited information is available about the pathogenesis of acquired immune
      deficiency syndrome (AIDS)-associated idiopathic interstitial pneumonitis, a
      common noninfectious complication of human immunodeficiency virus (HIV)
      infection. Infection of C57B1/6 mice with LP-BM5 retrovirus, a murine model of
      AIDS, leads to development of a diffuse interstitial pneumonitis that displays
      many features of human AIDS-associated interstitial pneumonitis. To further
      characterize the cellular and molecular features of this lung disease, the
      temporal development of cellular infiltration, cytokine expression, and virus
      replication were evaluated in lung tissue of virus-infected mice. Persistent
      expression of viral RNA was detectable in lungs as early as 1 wk after infection.
      Infiltration of the lungs by CD4+ and CD8+ T cells, by IgG+ and IgA+ B cells, and
      by macrophages was observed by 4 wk after infection and continued through 8 wk of
      infection. Histologically, cellular infiltration was most pronounced in
      peribronchial and perivascular regions, whereas inflammation of alveolar septae
      and alveolar spaces was minimal. In contrast to normals, T cells from infected
      lungs were immunodeficient in that they failed to proliferate in response to the
      mitogen concanavalin A (ConA). However, evaluation of cytokine mRNA expression by
      interstitial lung lymphoid cells indicated that cells from infected lungs were
      chronically activated, in that elevated expression of interferon-gamma (IFN
      gamma) and interleukin-10 (IL-10) was observed throughout the course of
      infection. Similarly, expression by interstitial lung lymphoid cells of mRNA for
      the proinflammatory cytokine IL-1 and the fibrogenic cytokine transforming growth
      factor-beta (TGF-beta) was also increased following infection. These results
      indicate that retrovirus-induced immunodeficiency in mice is associated with
      infiltration and chronic activation of lymphoid cells in the lungs. Furthermore,
      simultaneous expression of IL-10, IFN-gamma, and TGF-beta suggests that cytokine
      expressing cells in infected lungs may be unresponsive to inhibitory and
      antiinflammatory effects of IL-10 and/or TGF-beta, thus contributing to
      chronicity of inflammation in this disorder.

PMID- 9032123
TI  - Extracellular superoxide dismutase mRNA expressions in the human lung by in situ
      hybridization.
AB  - The extracellular form of superoxide dismutase (EC-SOD), SOD3, is contained in
      the human lung in relatively high amounts when compared to other organs. It has
      not been previously shown whether or not EC-SOD is synthesized and secreted by
      specific lung cells. We examined the expression of EC-SOD mRNA in human lung
      cells by in situ hybridization using a digoxigenin-labeled EC-SOD cRNA probe.
      Strong signals of EC-SOD synthesis were found in the epithelium of all airways.
      Secretory and basal cells, but not ciliated cells, were labeled for EC-SOD mRNA.
      Expression of EC-SOD mRNA was found in endothelial cells lining both arteries and
      veins. Many cells in the alveolar septum exhibited strong expression of EC-SOD
      mRNA. In addition, epithelial cells lining the outer wall of intrapulmonary
      airways and vessels were heavily labeled for EC-SOD mRNA. The lung parenchymal
      epithelial cells containing EC-SOD mRNA were identified as alveolar type II cells
      by colocalization with surfactant protein-A. Human alveolar macrophages were
      found to contain a substantial amount of EC-SOD mRNA expression. Alveolar type I
      epithelial cells and capillary endothelial cells did not display detectable
      signals of EC-SOD mRNA. Smooth muscle cells in muscular arteries were not labeled
      by the EC-SOD mRNA probe. These results show that airway epithelial cells and
      alveolar type II cells are the major cell types that synthesize fibroblasts EC
      SOD in the human lung. EC-SOD has been shown by immunocytochemistry to be
      associated with the extracellular matrix around airway epithelium and in the
      walls of intrapulmonary arterioles. The site of EC-SOD localization, therefore,
      is closely related to the site of its synthesis.

PMID- 9032124
TI  - Th1/Th2 cell distribution in pulmonary sarcoidosis.
AB  - Cytokines released by T lymphocytes activated in the course of sarcoidosis, e.g.,
      interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), indicate the presence of
      Th1 cells leading to the question of Th1/Th0/Th2 balance in sarcoidosis. The aim
      of this study was to evaluate Th-like cytokine patterns in different compartments
      of the body, i.e., peripheral blood, pulmonary parenchyma, and bronchoalveolar
      lavage (BAL), of patients with pulmonary sarcoidosis by comparing cytokine gene
      expression of 167 T-cell clones derived from the above-mentioned compartments.
      Seventy-nine blood, 49 transbronchial biopsy, and 39 BAL clones were analyzed
      using polymerase chain reaction to identify the respective gene transcripts. The
      majority of CD4+ and CD8+ blood cells exhibited intermediate cytokine profiles
      (63.3%) without shifts to either side of the spectrum (6.3% Th1, 5.1% Th2). Lung
      parenchyma cells shifted to the Th1 side of the spectrum: 26.5% of the cells were
      of Th1 or of intermediate type (between Th1 and Th0), whereas only 8.1% of the
      cells were of Th2 or of intermediate type (between Th0 and Th2). CD8+ parenchyma
      cells were evenly distributed. From BAL only CD4+ clones could be generated with
      shifts to both ends of the spectrum. Thus, our data provide evidence that in
      sarcoidosis, at the site of granuloma formation, an accumulation of Th1 cells as
      well as of intermediate (between Th1 and Th0) cell types occurs, whereas in the
      alveolar lumen, high numbers of Th1 and Th2 cells with a simultaneous decrease of
      Th0 cells can be observed.

PMID- 9032125
TI  - Differential responsiveness of human and rat mesothelioma cell lines to
      recombinant interferon-gamma.
AB  - Recombinant human interferon-gamma (r-hu-IFN-gamma) has been found to exert an
      antitumor action in vivo in early stages of human malignant mesothelioma, and an
      antiproliferative effect in vitro. In order to study the mechanisms of cytostasis
      in mesothelioma cells, we examined two IFN-gamma-controlled metabolic pathways
      known to mediate growth arrest in various cell types, measuring production of the
      antiproliferative compound nitric oxide (NO) and degradation of tryptophan in
      nine human mesothelioma cell lines (HMCLs) displaying different sensitivities to
      the antiproliferative effect of r-hu-IFN-gamma. Two rat mesothelioma cell lines
      were also studied. IFN-gamma receptor was present and functional in HMCLs,
      regardless of their sensitivity to the growth-inhibitory effect of r-hu-IFN
      gamma. However, no NO synthase activity or the resulting antiproliferative
      molecule NO were induced in HMCLs treated either with r-hu-IFN-gamma alone or
      with a combination of r-hu-IFN-gamma and other cytokines, and/or with
      lipopolysaccharide (LPS). In responsive HMCLs, r-hu-IFN-gamma induced strong
      indoleamine-2,3-dioxygenase (IDO) activity, which causes rapid degradation of
      tryptophan; however, the correlation between r-hu-IFN-gamma-mediated growth
      arrest and IDO induction was not absolute. In rat mesothelioma cells, NO synthase
      was induced in response to murine IFN-gamma + interleukin-1beta (IL-1beta)
      treatment, and played a role in the cytokine-mediated antiproliferative activity.
      However, NO production did not seem to be the unique antiproliferative mechanism
      induced by cytokines in these cells. Our results indicate that two classical
      pathways accounting for some of the cytostatic effects of IFN-gamma in rodent
      cells are not efficient in human mesothelioma cells, and suggest that cytokine
      induced growth inhibition is mediated by a different pathway in HMCLs.

PMID- 9032126
TI  - Elevated expression of endothelin-1 and endothelin-converting enzyme-1 in
      idiopathic pulmonary fibrosis: possible involvement of proinflammatory cytokines.
AB  - Endothelin-1 (ET-1) is a vasoconstrictor, bronchoconstrictor, and mitogenic
      peptide which is enzymatically converted from a biologically inactive big ET to
      mature ET (21 amino acid) by the ET-converting enzyme (ECE). Here, we investigate
      the expression of ECE-1, big ET-1, and ET-1 in the lungs of patients with
      idiopathic pulmonary fibrosis (IPF) and compare it to those of normal subjects
      using immunohistochemistry and in situ hybridization. In normal lungs, focal
      moderate expression of all three molecules is localized to airway epithelium,
      pulmonary endothelium, and airway and vascular smooth muscle cells. Serous
      bronchial glands also expressed ET-1 and ECE-1. In IPF, strong diffuse expression
      of ECE-1 was seen in airway epithelium, proliferating type II pneumocytes, and in
      endothelial and inflammatory cells. ECE-1 immunostaining was colocalized to big
      ET-1 and ET-1 immunostaining, and correlated with disease activity (P < 0.05). To
      study regulatory mechanisms of ET-1 and ECE-1 expression, human normal bronchial
      epithelial (NBE) cells were treated with cytokines and analyzed by
      radioimmunoassay and Northern blot. Incubation of human NBE cells with IL-1alpha
      and -beta or tumor necrosis factor alpha (TNFalpha) resulted in a significant
      increase in ET-1 release and mRNA expression. TNFalpha resulted in a significant
      increase in ECE-1 mRNA expression. These findings demonstrated the colocalization
      of the precursor and active ET-1, and ECE-1 in the same cell, and that ECE-1
      expression is elevated in IPF. In addition, increased expression of ET-1 and ECE
      1 in IPF may be mediated by proinflammatory cytokines.

PMID- 9032128
TI  - Effects of purine nucleotides and nucleoside on cytosolic calcium levels in rat
      tracheal smooth muscle cells.
AB  - Extracellular adenosine triphosphate (ATP) has a range of effects on a wide
      variety of cells through the activation of specific purinoceptors. The aim of
      this study was to establish whether P2 purinoceptors are present on airway smooth
      muscle cells. Experiments were conducted on cultured rat tracheal smooth-muscle
      cells (first through third passage). Intracellular Ca2+ ([Ca2+]i) was measured
      using Fura-2 and dual-excitation wavelength microfluorometry. The effects of ATP,
      adenosine diphosphate (ADP), uridine triphosphate (UTP), and adenosine (ADO) were
      measured in concentrations from 10(-6) to 10(-3) M. At a concentration of 10(-4)
      M, the peak [Ca2+]i was 502 +/- 92 nM for ATP and 543 +/- 76 nM for UTP (mean +/-
      standard error of the mean). ADO had no significant effect on Ca2+ release. Peak
      [Ca2+]i induced by ATP was not dependent on extracellular Ca2+ but was blocked by
      U-73122, an inhibitor of phospholipase C. Pretreatment with adenosine deaminase
      and desensitization with alphabeta-MeATP had no effect on ATP-induced Ca2+
      release. The effects of ATP (10(-4) M) on peak [Ca2+]i were potentiated by the
      presence of ADO 10(-5) M (969 +/- 257 nM; P < 0.05). The presence of XAC, a
      blocker of A1 and A2 ADO receptors did not prevent this effect. In the presence
      of XAC, ADO 10(-6) M potentiated the effects of ATP (peak [Ca2+]i: 1,300 +/- 229
      nM). The addition of 1433U83, a blocker of A3 ADO receptors, blocked the
      synergistic effect of ADO 10(-6) M on ATP. These data show that P2 purinoceptors,
      most likely of the P2U subtype, are present on airway smooth muscle cells and
      that the newly discovered A3 ADO receptor appears to be also present.

PMID- 9032127
TI  - ATP-induced mucin release from cultured airway goblet cells involves, in part,
      activation of protein kinase C.
AB  - Extracellular nucleotides stimulate mucin release by binding to the P2u receptor
      coupled to phospholipase C via G proteins (Br. J. Pharmacol. 103:1053-1056, 1991;
      Am. J. Respir. Cell Mol. Biol. 8:121-125, 1993). In the present study, we
      intended to investigate pathways downstream to the phospholipase C activation
      which is responsible for adenosine triphosphate (ATP)-induced mucin release in
      hamster tracheal epithelial cells in primary culture. We have found that: (1)
      Ca2+ ionophores (A23187 and ionomycin) did not affect mucin release even at 1
      microM; (2) thapsigargin (10 microM), either alone or in combination with ATP (20
      microM), did not enhance mucin release over its respective control group; (3)
      pretreatment of hamster tracheal surface epithelial (HTSE) cells with 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) (50
      microM) did not inhibit ATP-induced mucin release; (4) 4beta-phorbol 12alpha
      myristate 13-acetate (PMA, 1 microM) stimulated mucin release and its effect was
      completely blocked by protein kinase C inhibitors such as sphingosine (10 microM)
      and calphostin C (0.1 microM), whereas ATP-induced mucin release was blocked,
      only in part, by these inhibitors; (5) desensitization of protein kinase C by
      pretreatment with PMA inhibited the PMA-induced mucin release completely,
      however, ATP-induced mucin release was inhibited only partially. We conclude that
      mucin release by ATP does not require an increase in the intracellular Ca2+ level
      but involves the activation of protein kinase C. The results also suggest the
      presence of another mechanism separate from the phospholipase C-protein kinase C
      pathway for the ATP-induced mucin release.

PMID- 9032129
TI  - Drug receptor mechanisms in smooth muscle: beta-chloroethylamine-sensitive and 
      resistant receptor mechanisms.
AB  - Both alpha1-adrenoceptors and M3-cholinoceptors can be divided into two subtypes
      discriminated by the beta-chloroethylamines, chloroethylclonidine and
      propylbenzilylcholine mustard (PrBCM), only in the presence of GTP. The full
      agonists interact with both subtypes to induce responses. The partial agonists
      activate one of them to induce responses but behave as competitive antagonists
      when they interact with the other. The responses mediated through the receptors
      that are activated by the partial agonists are resistant to myosin light chain
      kinase inhibitors, while the response through the activation of the other
      receptors are suppressed by the inhibitors. The receptor stimulations through
      alpha1A-adrenoceptor and PrBCM-sensitive M3-cholinoceptor subtypes mainly
      activate the myosin light chain-phosphorylation-independent pathway mediated
      through protein kinase C and low molecular weight GTP-binding protein, whereas
      the stimulations through alpha1B-adrenoceptors and the PrBCM-phosphorylation
      dependent pathway are directly related to Ca2+/calmodulin.

PMID- 9032130
TI  - Dissociation of beta-adrenoceptor numbers from mRNA levels during acute ischemia
      in rat myocardium.
AB  - To explore alterations in messenger RNA (mRNA) for the beta-adrenoceptor (beta
      AR) in ischemic myocardium, we compared the mRNA levels for beta-AR in ischemic
      and nonischemic myocardium by in situ hybridization using a radioisotope imaging
      system. We also compared these mRNA levels in ischemic and nonischemic myocardium
      with the number of the beta-AR by radioligand binding assay. The mRNAs for beta
      AR were diffusely distributed in normal hearts. The level of mRNA detected by in
      situ hybridization was reduced by acute ischemia, whereas the number of beta-AR
      was increased. Although the number of beta-AR was increased in the myocardium
      with one or three hours ischemia, the total function in beta-AR-stimulatory G
      protein-adenylate cyclase system was not changed. There is a discrepancy between
      beta-AR mRNA and protein levels in the acute ischemic rat ventricular myocardium.

PMID- 9032131
TI  - Increase of Cl- secretion induced by Kampo medicine (Japanese herbal medicine),
      Sai-rei-to, in Mongolian gerbil middle ear epithelium.
AB  - Sai-rei-to, a type of Kampo medicine (Japanese herbal medicine), has been shown
      to be clinically effective in treating patients with otitis media with effusion.
      The effect of Sai-rei-to on the ion transport of the middle ear surface
      epithelium cultured from the Mongolian gerbil was investigated by using an Ussing
      chamber. Application of Sai-rei-to to the mucosal bath but not the serosal bath
      induced an increase in the short-circuit current (I(SC)) in the basal state. The
      increase in I(SC) was almost completely inhibited by addition of diphenylamine-2
      carboxylic acid but not by amiloride, indicating enhancement of Cl- secretion. On
      the basis of the lack of changes in the intracellular Ca2+ concentration and a
      sideness of action, the effect of Sai-rei-to on I(SC) is thought to be a direct
      and selective activation on the apical Cl- channel.

PMID- 9032132
TI  - Angiotensin II-induced pulmonary edema in a rabbit model.
AB  - We conducted the present study to propose a rabbit model of pulmonary edema (PE)
      induced by angiotensin II (AII) and to test the preventive effect of losartan on
      this form of PE. AII was administered to rabbits intravenously at 50, 100, 150 or
      300 microg/kg, either by continuous infusion (10 min) or by bolus injection (30
      sec). Continuously administered AII (150 microg/kg) induced PE in most cases,
      while a bolus injection of the same dosage did not. Additionally, the incidence
      of PE increased with higher dosages of AII when it was infused continuously. A
      newly established parameter, the area under the systolic blood pressure-time
      curve corrected by baseline (cAUC), was prone to rise as the incidence of PE
      increased. Moreover, cAUC signficantly correlated with the wet-dry lung weight
      ratio (r=0.66, P<0.05). Subsequently, 0.5 or 3.0 mg/kg of losartan was given
      before continuous infusion of 150 microg/kg of AII. The higher dosage of losartan
      prevented PE completely, while the lower one did so moderately. We concluded that
      intravenous administration of AII induces PE, probably as a result of increasing
      afterload. Furthermore, an adequate dosage of losartan can prevent PE because it
      reduces the pressor effect of AII.

PMID- 9032133
TI  - Pharmacological properties of YM17E, an acyl-CoA:cholesterol acyltransferase
      inhibitor, and diarrheal effect in beagle dogs.
AB  - YM17E (1,3-bis[[1-cycloheptyl-3-(p-dimethylaminophenyl)ureido]methyl]ben zene
      dihydrochloride) was found to be a potent inhibitor of acyl-CoA:cholesterol
      acyltransferase (ACAT) in rabbit liver and intestine microsomes. Dixon plot
      analysis revealed that YM17E inhibited microsomal ACAT in a non-competitive
      manner. YM17E induced a marked decrease in serum cholesterol, especially in non
      high-density lipoprotein (HDL) fractions, in cholesterol-fed rats and rats fed
      normal chow. Measurement of bile secretion after oral administration of YM17E in
      cholesterol-fed rats showed that the drug markedly accelerated the secretion of
      bile acids and neutral sterols. Furthermore, absorption of [3H]cholesterol from
      the gut of cholesterol-fed rats was significantly inhibited by YM17E. From these
      results, the hypocholesterolemic activity of YM17E in these animals resulted from
      both a decrease in cholesterol absorption from the gut and the stimulation of
      excretion of cholesterol from the liver into bile. However, YM17E caused
      secretory diarrhea in beagle dogs at near lipid lowering doses. When YM17E was
      administered at the same total dosage but divided into 5 daily administrations,
      the incidence of diarrhea was significantly reduced while its cholesterol
      lowering effect became stronger. These results suggest that the inhibition of
      intestinal and/or liver ACAT increases the risk of diarrhea development which,
      however, can be avoided by controlled drug administration in beagle dogs.

PMID- 9032134
TI  - Continuous infusion of beta-amyloid protein into the rat cerebral ventricle
      induces learning impairment and neuronal and morphological degeneration.
AB  - To investigate the toxicity of beta-amyloid protein, a component of the senile
      plaques in Alzheimer's disease, it was infused into the cerebral ventricle of
      rats for 14 days by a mini-osmotic pump. Performances in the water maze and
      passive avoidance tasks in beta-amyloid protein-treated rats were impaired.
      Choline acetyltransferase activity significantly decreased in the hippocampus
      both immediately and 2 weeks after the cessation of the infusion. However, the
      learning impairment was recoverable 2 weeks after cessation of the infusion. Both
      immediately and 2 weeks after the cessation of the infusion, glial fibrillary
      acidic protein immunoreactivity increased. Furthermore, beta-amyloid protein
      altered the staining in the nuclei of hippocampal cells for only 2 weeks after
      the cessation. These results suggest that beta-amyloid protein produces some
      damage in the central nervous system in vivo.

PMID- 9032135
TI  - Role of endogenous basic fibroblast growth factor in the healing of gastric
      ulcers in rats.
AB  - Recently, it has been pointed out that growth factors play an important role in
      the healing of gastrointestinal ulcers. In the present study, we examined the
      role of endogenous basic fibroblast growth factor (bFGF) in the healing of
      gastric ulcers in the rat. In male SD rats, gastric ulcers were induced in the
      antrum by injection of acetic acid. Time-dependent changes in the area and bFGF
      content in the ulcerated area and distribution of bFGF in the ulcerated mucosa
      were examined. Effects of bFGF mutein CS23 (TGP-580) and a monoclonal antibody
      for bFGF (MAb 3H3) on the healing of the gastric ulcers and angiogenesis in the
      ulcer bed were also examined. The content of bFGF in the ulcerated area increased
      with time as the ulcer healed and reached a maximum 7 days after ulcer formation.
      In the gastric ulcer bed, many cells such as fibroblasts and macrophages were
      positively stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1
      mg/rat/day, i.v.) inhibited angiogenesis in the ulcer bed and significantly
      delayed ulcer healing, while TGP-580 (0.001-0.1 mg/kg x 2/day, p.o.) increased
      the number of microvessels in the ulcer bed and accelerated the healing. These
      results suggest that endogenous bFGF may play an important role in the healing of
      gastric ulcers in the rat and that the angiogenic properties of bFGF (TGP-580)
      may be involved in its effect on ulcer healing.

PMID- 9032136
TI  - Modulation of anti-glomerular basement membrane nephritis in rats by ONO-1301, a
      non-prostanoid prostaglandin I2 mimetic compound with inhibitory activity against
      thromboxane A2 synthase.
AB  - The antinephritic effects of ONO-1301 ([7,8-dihydro-5-[(E)-[[a-(3
      pyridyl)benzylidene]-aminooxy]ethyl]-1 -naphtyloxy]acetic acid) on crescentic
      type anti-glomerular basement membrane (GBM) nephritis in rats were investigated.
      ONO-1301 was orally given to crescentic-type anti-GBM nephritic rats for 40 days
      after the induction of nephritis. ONO-1301 (30 mg/kg) suppressed the elevation of
      protein excretion into urine. In the ONO-1301-treated rats, cholesterol and urea
      nitrogen content in the plasma was lower than that of the nephritic control rats.
      Histological observation demonstrated that ONO-1301 suppressed the incidence of
      crescent formation and adhesion of capillary wall to Bowman's capsule. However,
      ONO-1301 failed to inhibit the antibody production against rabbit IgG and the rat
      IgG deposition on the GBM. The increase in very late antigen-4 (CD49b, VLA-4)
      positive cells in nephritic glomeruli was significantly reduced by ONO-1301
      treatment on day 5. cAMP-elevating agents inhibited the up-regulation of vascular
      cell adhesion molecule-1 (VCAM-1) expression on the surface of human umbilical
      vein endothelial cells (HUVECs) mediated by tumor necrosis factor (TNF)-alpha.
      These findings suggest that the antinephritic action of ONO-1301 is due to, at
      least in part, inhibition of intraglomerular accumulation of leukocytes through
      the prevention of the up-regulation of VCAM-1.

PMID- 9032137
TI  - Antihypertensive effect of repeatedly administered YM358, an angiotensin AT1
      receptor antagonist, in stroke-prone spontaneously hypertensive rats.
AB  - YM358 2,7-diethyl-5-[[2'-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[
      1,5-b][1,2,4]-triazole potassium salt), a novel nonpeptide angiotensin AT1
      receptor antagonist, was administered daily for 4 weeks to 24-week-old stroke
      prone spontaneously hypertensive rats (SHRSP). Its effects on systolic, mean and
      diastolic arterial pressure (SAP, MAP and DAP), heart rate and locomotor activity
      were investigated by using radiotelemetry. A clear diurnal variation in blood
      pressure, heart rate and locomotor activity was observed in synchrony with the
      light cycle. YM358 at a daily oral dose of 10 or 30 mg/kg produced a reduction of
      blood pressure in a dose-dependent manner. Although a mild attenuation of the
      antihypertensive effect of YM358 was observed during the early stage of therapy,
      YM358 at 30 mg/kg per day produced a significant and consistent decrease in 24-hr
      MAP and DAP, and it prevented the further development of hypertension. YM358 did
      not affect either heart rate or locomotor activity or their diurnal variations.
      After the discontinuation of therapy with YM358, the blood pressure recovered
      promptly to the control level while there was no sign of a rebound increase in
      blood pressure. These results suggest that YM358 may be potentially useful for
      the treatment of hypertension.

PMID- 9032138
TI  - Influences of ovariectomy and continuous replacement of 17beta-estradiol on the
      tail skin temperature and behavior in the forced swimming test in rats.
AB  - The effect of ovariectomy and continuous subcutaneous replacement of 17beta
      estradiol was examined in female Wistar rats. Tail skin temperature significantly
      increased in ovariectomized rats 6 days after ovariectomy, and the elevated level
      was sustained until 21 days after ovariectomy. 17beta-Estradiol at doses of 0.3
      and 1.0 microg/body/day suppressed the increases in tail skin temperature. In the
      forced swimming test, the ovariectomized control rats showed significantly
      prolonged immobility time in comparison with sham-ovariectomized rats 14 days
      after ovariectomy. The duration of immobility of ovariectomized rats treated with
      17beta-estradiol (0.3, 1.0, 3.0 microg/body/day) or maprotiline (0.6 mg/body/day)
      was significantly shorter than that of ovariectomized control rats.

PMID- 9032139
TI  - Protective effect of ifenprodil against glucose deprivation-induced damage in
      cultured rat hippocampal neurons.
AB  - When hippocampal cultures were deprived of glucose, massive release of lactate
      dehydrogenase (LDH), an indicator of neuronal death, occurred 24 hr following the
      onset of hypoglycemic insult via N-methyl-D-aspartate (NMDA)-type glutamate
      receptor activation. Ifenprodil (0.1 and 1 M) significantly inhibited LDH
      release, which was antagonized by polyamines. These results suggest that
      ifenprodil protects neurons from glucose deprivation by antagonizing the effects
      of glutamate via selective interaction with polyamine modulatory sites on the
      NMDA receptor complex. The observed phenomenon further indicate that ifenprodil
      might be used prophylactically against neuronal death induced by excitotoxic
      disorders.

PMID- 9032140
TI  - beta1-Adrenoceptor-mediated relaxation by norepinephrine in dog hepatic arteries.
AB  - Dog hepatic arterial strips treated with prazosin responded to norepinephrine
      with concentration-related, endothelium-independent relaxations, the maximal
      response being 81.7% of the papaverine-induced maximal relaxation that was
      markedly greater than that in renal arteries. The norepinephrine-induced
      relaxation in hepatic arteries was significantly attenuated by metoprolol but not
      influenced by butoxamine. Relaxant responses to norepinephrine of dog hepatic
      arteries appear to be mediated by the beta1-adrenoceptor subtype, like those of
      coronary arteries. Evidence for functioning of the beta1-subtype in hepatic
      arteries would contribute to the analysis of neural and hormonal regulation of
      blood flow in the liver.

PMID- 9032141
TI  - A piece of my mind. A rude awakening.

PMID- 9032143
TI  - Determination of serum creatinine level prior to administration of radiographic
      contrast media.

PMID- 9032142
TI  - Wound care following needlestick injuries.

PMID- 9032144
TI  - Loading dose of digoxin.

PMID- 9032145
TI  - NIH consensus panel spurs discontent.

PMID- 9032146
TI  - Justice Department calls medicare payments to Christian Science sanitoria
      unconstitutional.

PMID- 9032147
TI  - From the Centers for Disease Control and Prevention. Paralytic poliomyelitis-
      United States, 1980-1994.

PMID- 9032148
TI  - From the Centers for Disease Control and Prevention. Injuries and deaths
      associated with use of snowmobiles--Maine, 1991-1996.

PMID- 9032149
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States, 1996-97 season.

PMID- 9032150
TI  - Treatment of patients with non-insulin-dependent diabetes with the implantable
      insulin pump.

PMID- 9032151
TI  - Treatment of patients with non-insulin-dependent diabetes with the implantable
      insulin pump.

PMID- 9032152
TI  - Treatment of patients with non-insulin-dependent diabetes with the implantable
      insulin pump.

PMID- 9032153
TI  - Risk-adjustment methods based on health status and functional status.

PMID- 9032154
TI  - Medical examiners, forensic pathologists, and coroners.

PMID- 9032155
TI  - Recognition of cigarette advertisement product logos.

PMID- 9032156
TI  - Is hepatitis G virus transmitted sexually?

PMID- 9032157
TI  - Genetic polymorphisms and breast cancer risk.

PMID- 9032158
TI  - Genetic polymorphisms and breast cancer risk.

PMID- 9032160
TI  - Timing of postmenopausal estrogen for optimal bone mineral density. The Rancho
      Bernardo Study.
AB  - OBJECTIVE: To determine the effect of the timing of initiation and the duration
      of postmenopausal estrogen therapy on bone mineral density (BMD). DESIGN: Cross
      sectional study. SETTING: White, middle-class to upper middle-class community
      dwelling women. PARTICIPANTS: A total of 740 women aged 60 to 98 years who
      participated in a study of osteoporosis. MEASUREMENTS: Questionnaire, validated
      medication use, and height and weight. Bone mineral density at the ultradistal
      radius and midshaft radius using single-photon absorptiometry (SPA) and at the
      hip and lumbar spine using dual-energy x-ray absorptiometry (DEXA). RESULTS: Of
      the 740 women, 69% had used oral estrogen after menopause and 30% were current
      users. Five groups of estrogen use were identified: never users, past users who
      started at menopause, past users who started after age 60 years, current users
      who started after age 60 years, and current users who started at menopause. At
      all 4 bone sites, current users who started at menopause had the highest BMD
      levels, which were significantly higher than never users or past users who
      started at menopause (with 10 years' duration of use). These differences
      persisted after controlling for all major risk factors for osteoporosis. Among
      current users, there was no significant difference in BMD levels at any site
      between those who started estrogen at menopause (with 20 years of use) and those
      who started after age 60 years (with 9 years of use). CONCLUSIONS: Estrogen
      initiated in the menopausal period and continued into late life is associated
      with the highest bone density. Nevertheless, estrogen begun after age 60 years
      and continued appears to offer nearly equal bone-conserving benefit.

PMID- 9032159
TI  - The recent decline in mortality from coronary heart disease, 1980-1990. The
      effect of secular trends in risk factors and treatment.
AB  - OBJECTIVE: To examine whether secular trends in risk factor levels and
      improvements in treatment can account for the observed decline in coronary heart
      disease mortality in the United States from 1980 to 1990 and to analyze the
      proportional contribution of these changes. DATA SOURCES: Literature review, US
      statistics, health surveys, and ongoing clinical trials. STUDY SELECTION: Data
      representative of the US situation nationwide reported in adequate detail. DATA
      EXTRACTION: A computer-simulation state-transition model of the US population
      between the ages of 35 and 84 years was developed to forecast coronary mortality.
      The input variables were estimated such that the combination of values led to an
      adequate agreement with reported coronary mortality figures. Subsequently,
      secular trends were modeled. DATA SYNTHESIS: Actual coronary mortality in 1990
      was 34% (127,000 deaths) lower than would be predicted if risk factor levels,
      case-fatality rates, and event rates in those with and without coronary disease
      remained the same as in 1980. When secular changes in these factors were included
      in the model, predicted coronary mortality in 1990 was within 3% (10,000 deaths)
      of the observed mortality and explained 92% of the decline; only 25% of the
      decline was explained by primary prevention, while 29% was explained by secondary
      reduction in risk factors in patients with coronary disease and 43% by other
      improvements in treatment in patients with coronary disease. CONCLUSIONS: These
      results suggest that primary and secondary risk factor reductions explain about
      50% of the striking decline in coronary mortality in the United States between
      1980 and 1990 but that more than 70% of the overall decline in mortality has
      occurred among patients with coronary disease.

PMID- 9032161
TI  - Predictors of red cell folate level in women attempting pregnancy.
AB  - OBJECTIVE: To identify predictors of red cell folate level in women attempting to
      become pregnant. DESIGN: Cohort study. SETTING: A health maintenance organization
      serving the Minneapolis-St Paul, Minn, area. PARTICIPANTS: A total of 189
      healthy, primarily white women aged 22 to 35 years enrolled in the Diana Project,
      a population-based prospective study of preconceptional and prenatal risks to
      reproductive outcomes. The sample represents 189 of 219 enrolled women who were
      sequentially selected from the total Diana Project sample to receive additional
      laboratory analyses. MAIN OUTCOME MEASURE: Red cell folate level. RESULTS: Folic
      acid supplements, folic acid intake from fortified cereals, vitamin C
      supplements, and serum zinc level (inverse) were found to predict red cell folate
      levels. Previous research has shown that red cell folate levels higher than 906
      nmol/L (400 ng/mL) may be optimal for the prevention of folate-responsive neural
      tube defects. For folic acid supplement users, folate intakes of 450 microg per
      day and higher corresponded to these protective levels of red cell folate. In
      nonusers of supplements, intakes of more than 500 microg of folate per day from
      foods and folic acid-fortified cereals may be needed to attain red cell folate
      levels higher than 906 nmol/L (400 ng/mL). Red cell folate levels higher than 906
      nmol/L (400 ng/mL) were primarily found in women who took folic acid supplements.
      Only 1 in 4 women had red cell folate levels higher than 906 nmol/L (400 ng/mL),
      while 1 in 8 had red cell folate levels indicative of a negative folate balance.
      Addition of a daily, 400-microg folic acid supplement to the usual diet would
      result in red cell folate levels over 906 nmol/L (400 ng/mL) in a majority of
      women in this study. CONCLUSIONS: Supplementation of diets of women of
      childbearing potential with 400 microg of folic acid per day would effectively
      raise red cell folate to levels associated with a low risk of folate-responsive
      neural tube defects. Protective levels of red cell folate may also be obtained by
      ample consumption of vegetables, fruits, and folic acid-fortified breakfast
      cereals. Efforts to increase folic acid supplement use and folate consumption
      among women of childbearing potential must go beyond fortification of refined
      cereal and grain products and reach women within all educational and income
      groups.

PMID- 9032162
TI  - Physician-patient communication. The relationship with malpractice claims among
      primary care physicians and surgeons.
AB  - OBJECTIVE: To identify specific communication behaviors associated with
      malpractice history in primary care physicians and surgeons. DESIGN: Comparison
      of communication behaviors of "claims" vs "no-claims" physicians using audiotapes
      of 10 routine office visits per physician. SETTINGS: One hundred twenty-four
      physician offices in Oregon and Colorado. PARTICIPANTS: Fifty-nine primary care
      physicians (general internists and family practitioners) and 65 general and
      orthopedic surgeons and their patients. Physicians were classified into no-claims
      or claims (> or =2 lifetime claims) groups based on insurance company records and
      were stratified by years in practice and specialty. MAIN OUTCOME MEASURES:
      Audiotape analysis using the Roter Interaction Analysis System. RESULTS:
      Significant differences in communication behaviors of no-claims and claims
      physicians were identified in primary care physicians but not in surgeons.
      Compared with claims primary care physicians, no-claims primary care physicians
      used more statements of orientation (educating patients about what to expect and
      the flow of a visit), laughed and used humor more, and tended to use more
      facilitation (soliciting patients' opinions, checking understanding, and
      encouraging patients to talk). No-claims primary care physicians spent longer in
      routine visits than claims primary care physicians (mean, 18.3 vs 15.0 minutes),
      and the length of the visit had an independent effect in predicting claims
      status. The multivariable model for primary care improved the prediction of
      claims status by 57% above chance (90% confidence interval, 33%-73%).
      Multivariable models did not significantly improve prediction of claims status
      for surgeons. CONCLUSIONS: Routine physician-patient communication differs in
      primary care physicians with vs without prior malpractice claims. In contrast,
      the study did not find communication behaviors to distinguish between claims vs
      no-claims surgeons. The study identifies specific and teachable communication
      behaviors associated with fewer malpractice claims for primary care physicians.
      Physicians can use these findings as they seek to improve communication and
      decrease malpractice risk. Malpractice insurers can use this information to guide
      malpractice risk prevention and education for primary care physicians but should
      not assume that it is appropriate to teach similar behaviors to other specialty
      groups.

PMID- 9032163
TI  - Managed care. A product of market dynamics.
AB  - The development of managed care is described as an unexpected product of
      competition between public and private purchasers of health care. Managed care is
      a series of purchasing techniques that employers have applied to reduce the cost
      of their employees' health benefits. Its most significant use has been as a
      device for bargaining with individual health care providers by encouraging or
      requiring employees to purchase health care services from a select set of
      providers. Selective contracting has broken a 40-year-old barrier to price
      competition among health care providers, who have responded to this negotiating
      tactic by forming or joining larger organizational units to strengthen their
      bargaining power. Although the so-called managed care revolution has reduced the
      rate of increase in health care costs by creating a more competitive price
      environment, it is simply a start toward a more effective health care market. It
      is very much a work in progress that will affect and be affected by both
      political and market changes occurring over the remainder of this century.

PMID- 9032164
TI  - Does this patient have an abnormal systolic murmur?
AB  - Our objective was to review the available evidence of the precision and accuracy
      of the clinical examination for abnormal systolic murmurs. We conducted a MEDLINE
      search, manually reviewed all reference lists, and contacted authors of published
      studies. Each study was independently reviewed by 2 observers and graded for
      methodologic quality. We found that most studies were conducted using
      cardiologist examiners. In the clinical setting, the reliability of detecting
      systolic murmurs was fair (kappa, 0.30-0.48). The most useful findings for ruling
      in aortic stenosis are a slow rate of rise of the carotid pulse (positive
      likelihood ratio, 2.8-130), mid to late peak intensity of the murmur (positive
      likelihood ratio, 8.0-101), and decreased intensity of the second heart sound
      (positive likelihood ratio, 3.1-50). The most useful finding for ruling out
      aortic stenosis is the absence of murmur radiation to the right carotid artery
      (negative likelihood ratio, 0.05-0.10). Smaller, lower-quality studies indicate
      that cardiologists can accurately rule in and rule out mitral regurgitation,
      tricuspid regurgitation, hypertrophic cardiomyopathy, and echocardiographic
      mitral valve prolapse. We conclude that the clinical examination by cardiologists
      is accurate for detecting various causes of abnormal systolic murmurs. Studies of
      the clinical examination by noncardiologists are needed.

PMID- 9032165
TI  - The clinical examination. An agenda to make it more rational.

PMID- 9032166
TI  - Symptoms of anxiety and depression as precursors to hypertension.

PMID- 9032167
TI  - California public hospitals. The buck has stopped.

PMID- 9032168
TI  - Multiple Risk Factor Intervention Trial. Risk factor changes and mortality
      results. Multiple Risk Factor Intervention Trial Research Group. 1982.

PMID- 9032169
TI  - The Multiple Risk Factor Intervention Trial (MRFIT). A return to a landmark
      trial.

PMID- 9032170
TI  - For every thing (turn...turn...turn....)

PMID- 9032171
TI  - Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.

PMID- 9032172
TI  - Phospholipase A2 and arachidonate increase in bronchoalveolar lavage fluid after
      inhaled antigen challenge in asthmatics.
AB  - Phospholipases A2 (PLA2) hydrolyze phospholipids resulting in the release of
      fatty acids including arachidonic acid (AA) and lysophospholipids. AA, in turn,
      serves as a substrate for the synthesis of leukotrienes which can cause
      bronchoconstriction and airways edema and appear to be important mediators of
      clinical asthma. Further, lysophospholipids may be cytotoxic and/or impair the
      function of surfactant. We examined the release of secretory PLA2 (sPLA2) and AA
      into the airways after antigen challenge in 16 subjects with allergic asthma.
      Asthmatic subjects underwent bronchoscopy with bronchoalveolar lavage (BAL)
      before and after inhaled antigen challenge; in addition, a single BAL, without
      inhaled antigen, was performed in 10 control subjects. BAL was obtained at 4 h (n
      = 7), the time of the late asthmatic response (LAR) (n = 5), or 24 h (n = 4)
      after challenge. There was no difference between normal and asthmatic subjects in
      either BAL fluid (BALF) sPLA2 activity or AA concentration at baseline. Both
      sPLA2 and AA increased after antigen challenge (p < 0.01 and 0.05, respectively).
      These changes were most marked 4 h after challenge (p < 0.03 for both). sPLA2 may
      play an important role in the generation of AA in patients with asthma.

PMID- 9032173
TI  - Bilateral increases in histamine after unilateral nasal allergen challenge.
AB  - Studying the inflammatory response that follows the early response to nasal
      challenge with antigen provides a better understanding of allergic rhinitis than
      just studying the immediate (early) response. Nine allergic volunteers were
      challenged unilaterally with antigen-containing discs, and bilateral changes in
      physiologic responses as well as in the concentration of histamine in nasal
      secretions were measured for 11 h. We found significant immediate increases in
      symptoms, sneezes, ipsilateral nasal airway resistance, and ipsilateral histamine
      in the early phase response. Two-thirds of the allergen-challenged volunteers
      showed increases in physiologic parameters or histamine in the hours after
      allergen challenge. The pooled data of all subjects exhibited significant
      increases in bilateral nasal airway resistance and in ipsilateral and
      contralateral histamine, hours after unilateral provocation. These responses
      differed significantly from control subjects. In another group of 11 volunteers
      challenged ipsilaterally with antigen, the number of basophils increased both on
      the side of challenge and on the contralateral side. The magnitude of the
      increase on the ipsilateral side correlated with the increase on the
      contralateral side (r(s) = 0.72). The basophils are the most likely source of the
      contralateral increase in histamine as they are on the ipsilateral side. Although
      the mechanisms underlying this contralateral increase in basophils and histamine
      are not known, we speculate that delayed, neurogenic responses play a
      contributory role.

PMID- 9032174
TI  - Levels of amino acids and related compounds in bronchoalveolar lavage fluids of
      asthmatic patients.
AB  - The constituents of bronchoalveolar lavage (BAL) fluid have been shown to reflect
      the presence and possible etiology of several pulmonary diseases. Presently,
      although research studies have reported the concentrations of cytokines and
      compounds such as major basic protein in BAL fluids, only the cellular elements,
      total protein, albumin, and immunoglobulins have been well defined. We
      hypothesize that amino acids and related amino compounds, well known participants
      in physiologic and biochemical processes, are present in BAL fluid and may have
      involvement in asthma. Our objective was to extend knowledge of the total
      chemical profile and clinical value of BAL fluids in humans by measuring these
      amino compounds in normal control subjects and asthmatic patients. Analysis by
      high-pressure liquid chromatography revealed the presence of 25 compounds. A few
      compounds in control subjects and patients were found to have values > 1.0
      nmol/ml, while the majority were present in comparatively low concentrations <
      1.0 nmol/ml. Asparagine, phosphoethanolamine, and taurine were significantly
      increased in the asthmatic patients. We conclude that the present profile of
      amino acids and related amino compounds in BAL fluid serves as a potential
      diagnostic tool in the study of various pulmonary disorders. The significance of
      increased asparagine, phosphoethanolamine, and taurine in the asthmatic patients
      is discussed and deserves further study.

PMID- 9032175
TI  - 8-Epi-PGF2alpha induces airflow obstruction and airway plasma exudation in vivo.
AB  - 8-Epi-prostaglandin F2alpha (8-epi-PGF2alpha) is an F2-isoprostane formed mainly
      via noncyclooxygenase pathways in vivo. We investigated whether 8-epi-PGF2alpha
      has any effect on airflow obstruction and plasma exudation in vivo. Airflow
      obstruction was quantified by measuring lung resistance (RL) in anesthetized and
      ventilated guinea pigs, and plasma exudation was quantified by the Evans Blue dye
      method (20 mg/kg intravenously). Intratracheal instillation of 8-epi-PGF2alpha (1
      nmol or 10 nmol) caused dose-related increases in RL. Furthermore, the higher
      dose of 8-epi-PGF2alpha produced Evans Blue dye extravasation in main bronchi and
      intrapulmonary airways. A prostanoid TP-receptor antagonist, BAY u3405 (1 mg/kg
      intravenously), abolished the airway effects of 8-epi-PGF2alpha (10 nmol). A
      thromboxane A2 (TxA2) synthase inhibitor, OKY-406 (30 mg/kg intravenously),
      significantly attenuated these effects of 8-epi-PGF2alpha (10 nmol). The level of
      TxB2, a stable TxA2 metabolite, increased in bronchoalveolar lavage fluid (BALF)
      after 8-epi-PGF2alpha instillation. We conclude that 8-epi-PGF2alpha causes
      airflow obstruction and plasma exudation in vivo. This effect may be mediated
      primarily via prostanoid TP-receptors, and a secondary generation of TxA2 may be
      involved in part of the airway responses in 8-epi-PGF2alpha in the guinea pig.

PMID- 9032176
TI  - Kinetics of the development and recovery of the lung from IgE-mediated
      inflammation: dissociation of pulmonary eosinophilia, lung injury, and eosinophil
      active cytokines.
AB  - Events occurring up to 16 d after antigen challenge were characterized using a
      novel protocol employing four bronchoscopies, two segmental antigen challenge
      (SAC) procedures (on Days 1 and 2), and six bronchoalveolar lavages (BALs) (on
      Days 1, 2, 9, and 16) in three groups: ragweed allergic asthmatics with dual
      phase airway reactions (AA-D), allergic asthmatics with a single early airway
      reaction (AA-S), and nonallergic nonasthmatic control subjects. In AA-D subjects,
      SAC produced a marked eosinophilic inflammatory response at 24 h associated with
      eosinophil degranulation (eosinophil cationic protein [ECP] in BAL fluid) and
      lung injury, which largely resolved by Day 16. When the second antigen-challenged
      segment (SAC performed on Day 2) was lavaged 7 d after challenge (Day 9), a
      persistent pulmonary eosinophilia was noted accompanied by minimal elevations in
      ECP and albumin. Eosinophil-active cytokines showed unique patterns: interleukin
      5 (IL-5) increased in the antigen segment on Day 2 then returned to baseline
      after 7 d; granulocyte-macrophage colony-stimulating factor (GM-CSF) peaked at
      Day 2 but was persistently elevated throughout Day 16 in antigen segments, and
      increased in control segments at late time points; IL-3 levels were constant and
      similar in antigen and control segments. Changes were specific to AA-D subjects
      in comparison with control subjects. Elements of the IgE-mediated pulmonary
      inflammatory response differ markedly in their development and resolution.

PMID- 9032177
TI  - Granulocyte activation markers in induced sputum: comparison between chronic
      obstructive pulmonary disease, asthma, and normal subjects.
AB  - Airway inflammation is present in asthma and is thought to play a significant
      part in the development of airflow obstruction. In chronic obstructive pulmonary
      disease (COPD), neutrophilic inflammation is present in the airway lumen, whereas
      the submucosa displays a lymphocytic infiltrate. Less is known about the nature
      and mechanisms of inflammation in COPD than in asthma. Induced sputum allows
      noninvasive sampling of respiratory tract secretions from patients and control
      subjects, allowing characterization of cells and measurement of soluble markers.
      We exploited this technique in order to compare the presence and quantify
      specific markers of eosinophil and neutrophil activation in subjects with asthma
      or COPD, and control subjects. Differential cell counts showed significantly
      higher neutrophil percentages in the patients with COPD compared with other
      groups, while patients with asthma had higher numbers of eosinophils. The
      neutrophil markers myeloperoxidase (MPO), from primary granules in neutrophils,
      and human neutrophil lipocalin (HNL), released from secondary granules, were
      elevated in patients with asthma and COPD compared with control subjects but
      markedly more so in COPD. The difference between COPD and asthma was more marked
      for HNL than for MPO suggesting that HNL may be a better marker for
      discriminating between these conditions. Concentrations of the eosinophil granule
      protein, eosinophil cationic protein (ECP), and the eosinophil granule-derived
      enzyme, eosinophil peroxidase (EPO) were raised in the patients with asthma and
      those with COPD.

PMID- 9032178
TI  - Observations on the effects of aerosolized albuterol in acute asthma.
AB  - To determine the dose of albuterol required to terminate acute episodes of
      asthma, 92 acutely ill subjects received three doses of 2.5 mg each by
      nebulization every 20 min. Peak expiratory flow rates (PEFR) and signs and
      symptoms were serially monitored. A dose-response increase in pulmonary function
      was found, but only 66% of the subjects improved sufficiently to be sent home. Of
      these, 56% required < or = 5.0 mg of drug to reach the discharge threshold,
      whereas the remainder needed 7.5 mg. In 34% of participants, albuterol was
      ineffectual. These individuals were characterized by more severe obstruction at
      presentation, and after three doses of medication their PEFR still did not exceed
      40% of the expected value. Further treatment in the emergency department (ED) or
      hospital was not immediately helpful, and these patients ultimately required 3.8
      +/- 0.4 d of inpatient care to become asymptomatic. There were no discernible
      differences between responders and nonresponders in the type or quantity of
      medications used. However, the nonresponders had more severe disease as measured
      by recurrent hospitalizations and ED visits. This study demonstrates that, in
      emergency situations, albuterol does not relieve acute airway obstruction in all
      asthmatic individuals with equal efficacy. Two-thirds of patients are sensitive,
      and in these patients 5 to 7.5 mg of albuterol provides optimal treatment. In the
      remainder, albuterol, even in high doses, has little effect for days.

PMID- 9032179
TI  - Airway anesthesia and respiratory adaptations to dead space loading and exercise.
AB  - In exercising humans, added external dead space (VD) increases minute ventilation
      (VI) and causes a slower and deeper breathing pattern (J. Appl. Physiol. 1991;
      70:55-62). Recent studies suggest that airway receptors sensitive to topical
      anesthesia influence VI and breathing pattern responses to exercise and to added
      VD. We tested these hypotheses with a technique of airway anesthesia (Anesthesia)
      that has been shown to reliably attenuate airway reflexes. Anesthesia was
      administered by local laryngopharyngeal application and aerosolized lidocaine
      inhalation, and was confirmed by citric acid aerosol inhalation challenges.
      Twelve normal males performed maximal incremental cycle ergometer exercise on 4 d
      (randomized) after Anesthesia with (Anesthesia VD) and without added VD
      (Anesthesia Control) and after normal saline inhalation (Saline) with (Saline VD)
      and without added VD (Saline Control). There were no differences in the VI and
      breathing pattern responses during exercise between the Saline Control and the
      Anesthesia Control tests. After both Saline and Anesthesia inhalation, added VD
      resulted in an increase in VI both at rest and during exercise. At matched VI (98
      L/min), the differences in tidal volume (VT) between the Saline Control and
      Saline VD tests (delta = 0.23 +/- 0.24 L, mean +/- SD) and the Anesthesia Control
      and Anesthesia VD tests (delta = 0.20 +/- 0.28 L) were not significantly
      different. Our study had a power of greater than 95% to detect significant
      differences in VI or breathing pattern due to Anesthesia. We conclude that in
      normal humans, airway receptors do not play a major role in ventilation and
      breathing pattern control during exercise, and that the respiratory adaptations
      to added VD during exercise are not mediated by airway afferent reflexes.

PMID- 9032181
TI  - Prone position in mechanically ventilated patients with severe acute respiratory
      failure.
AB  - The purpose of this study was to characterize changes in oxygenation, expressed
      as PaO2/F(I)O2, when patients with severe acute respiratory failure (PaO2/F(I)O2
      < 150), unrelated to left ventricular failure to atelectasis, were turned to and
      from a supine to prone position at 1- and 4-h intervals. Ventilator settings were
      unchanged. Thirty-two consecutive patients were studied 1 h before, 1 and 4 h
      during and 1 h after placing in a prone position with PaO2/F(I)O2 of 103 +/- 28,
      158 +/- 62, 159 +/- 59, and 128 +/- 52, respectively (ANOVA, p < 0.001). After 1
      h in a prone position, improvement of PaO2/F(I)O2 by 20 mm Hg or more was
      considered a positive response. Seven patients studied had no response (22%),
      hereafter referred to as nonresponders, and 25 had a positive response (78%),
      hereafter referred to as responders. Among the seven nonresponders, two did not
      tolerate the prone position and were returned supine before the end of the 4-h
      trial. With the remaining five, PaO2/F(I)O2 evolution was 83 +/- 29, 77 +/- 19,
      83 +/- 33, and 81 +/- 47, respectively. For two of the 25 responders,
      measurements are missing after returning to the supine position. In 10 of the 23
      responders (43%) who completed the 4 h prone trial, the PaO2/F(I)O2 returned to
      its starting value when patients were repositioned supine: 117 +/- 24, 164 +/-
      44, 156 +/- 55, and 110 +/- 34, respectively (ANOVA, p < 0.01). In 13 of the 23
      (57%) improvement persisted: 105 +/- 27, 187 +/- 58, 189 +/- 49, and 157 +/- 49,
      respectively (ANOVA, p < 0.001). Repeated improvements after turning to a prone
      position were frequently observed. Side effects in the 32 patients after a total
      of 294 periods in a prone position included minor skin injury and edema, two
      instances of apical atelectasis, one catheter removal, one catheter compression,
      one extubation, and one transient supraventricular tachycardia.

PMID- 9032180
TI  - Cell infiltration, ICAM-1 expression, and eosinophil chemotactic activity in
      asthmatic sputum.
AB  - We have applied the technique of sputum induction by hypertonic saline in
      asthmatics and nonatopic control subjects to study an array of indices of airway
      inflammation believed to be relevant to asthma pathogenesis. Compatible with a
      central role for eosinophils and mast cells in asthma, sputum of asthmatic
      subjects contained increased numbers of eosinophils and levels of eosinophil
      cationic protein (ECP) and mast cell tryptase. Eosinophil numbers, and ECP and
      histamine levels correlated with the degree of methacholine airways
      responsiveness, and ECP, tryptase, and histamine correlated with raised
      concentrations of albumin. Using the micro-Boyden chamber technique eosinophil
      chemotactic activity was identified only in the sputum from asthmatics. The
      correlation between the raised levels of total IgA, IL-8/IgA complexes, and
      tryptase and the degree of sputum eosinophilia and ECP levels, suggests possible
      mechanisms for eosinophil chemotaxis and activation in asthma. Row cytometric
      analysis of sputum lymphocytes showed an increase in CD4+ T cells and T cells
      expressing intercellular adhesion molecule-1 (ICAM-1) in asthma which, together
      with the finding of raised levels of soluble ICAM-1 in the sputum, indicates
      upregulation of this adhesion molecule. Finally, the proportion of CD16+ natural
      killer (NK) cells was reduced in the sputum of asthmatics. These observations
      highlight the importance of the airway inflammation in causing asthma and further
      confirm the usefulness of sputum induction as a tool in asthma research.

PMID- 9032183
TI  - The determinants of respiratory rate during mechanical ventilation.
AB  - The independent and interactive effect of feedback related to volume, CO2,
      inspiratory flow, and arousal state on the regulation of respiratory rate in
      mechanically ventilated humans is not well characterized. We examined the rate
      response of eight normal volunteers during both quiet wakefulness and non-rapid
      eye-movement (NREM) sleep, while mechanically ventilated through a nasal mask in
      an assist/control mode with a machine back-up rate of 2 breaths/min. Tidal volume
      (VT) was set slightly above spontaneous VT and then increased by 0.2 L every 3
      min up to 1.8 L or 25 ml/kg. Either an inspiratory flow of 40 L/min or an
      inspiratory time of 2 s (iso-T(I)) was set, with CO2 added (F(I)CO2 > 0) or
      F(I)CO2 = 0. Measurements were made during both quiet wakefulness and NREM sleep.
      We found that as VT increased, the respiratory rate decreased; the rate decline
      was observed during wakefulness and sleep, and under isocapnic as well as
      hypocapnic conditions. Increasing inspiratory flow raised the respiratory rate
      during wakefulness and NREM sleep. During NREM sleep, hypocapnia resulted in
      wasted ventilator trigger efforts. In summary, both VT and inspiratory flow
      settings affect the respiratory rate, and depending on state, can affect CO2
      homeostasis. Ventilator settings appropriate for wakefulness may cause
      ventilatory instability during sleep.

PMID- 9032182
TI  - Plasma hypoxanthine levels in ARDS: implications for oxidative stress, morbidity,
      and mortality.
AB  - Acute respiratory distress syndrome in adults (ARDS) carries a high mortality.
      Patients with ARDS experience severe oxidative stress from neutrophil activation,
      and from treatment with high inspired oxygen concentrations (F(I)O2). Oxidative
      stress arises from an increased generation of reactive oxygen species (ROS) which
      overwhelm existing antioxidant defenses. Patients who do not survive ARDS sustain
      much greater levels of oxidative molecular damage, suggesting that they are less
      able to protect themselves against increased oxidative stress. We measured plasma
      levels of pro-oxidant substrates for xanthine oxidase, namely hypoxanthine and
      xanthine, and correlated them with the loss of plasma protein thiol groups. All
      patients with ARDS had higher levels of hypoxanthine (37.48 +/- 3.1 microM in
      nonsurvivors, 15.24 +/- 2.09 microM in survivors) compared with patients
      undergoing pulmonary resection (9.22 +/- 1.89 microM), patients in intensive care
      with sepsis but no lung injury (1.12 +/- 0.69 microM) and normal healthy control
      subjects (1.43 +/- 0.38 microM). The difference in plasma hypoxanthine levels
      between survivors and nonsurvivors of ARDS was highly significant (p < 0.001) and
      showed a negative correlation with loss of protein thiol groups. Xanthine levels
      were also higher in patients with ARDS but were not significantly different
      between ARDS survivors and nonsurvivors. Nonsurvivors of ARDS appear to
      experience higher levels of oxidative stress and damage than do survivors.

PMID- 9032184
TI  - Ventilation strategies affect surfactant aggregate conversion in acute lung
      injury.
AB  - This study evaluated the effects of varying tidal volumes (VT) and positive end
      expiratory pressure (PEEP) levels on surfactant aggregate conversion and lung
      function in an animal model of lung injury induced by N-nitroso-N-methylurethane.
      Lung-injured adult rabbits were initially ventilated using a VT of 10 ml/kg
      (VT10), a respiratory rate of 30 breaths/min (RR30), and a PEEP of 3.5 cm H2O. A
      trace dose of radiolabeled rabbit large surfactant aggregates was instilled after
      the onset of ventilation, and animals were then ventilated at different
      ventilator settings for 1 h. Ventilation strategies involving a lower VT (VT5,
      RR60) resulted in significantly superior oxygenation and lower surfactant
      aggregate conversion rates than strategies involving a higher VT ([VT10, RR30],
      [VT15, RR20], p < 0.05). Increasing the PEEP level to 8.0 cm H2O improved
      oxygenation, but it was sustained only with a low VT (VT5, RR60), and
      deteriorated with a high VT (VT10, RR30). Varying VT but not PEEP levels resulted
      in significant changes in surfactant aggregate conversion. We conclude that
      increased surfactant aggregate conversion resulting from suboptimal ventilation
      of injured lungs may play an important role in the pathophysiology of ventilation
      induced lung dysfunction in acute lung injury.

PMID- 9032185
TI  - Ventilatory and hemodynamic effects of continuous positive airway pressure in
      left heart failure.
AB  - The ventilatory and hemodynamic effects of continuous positive airway pressure
      (CPAP) delivered via a face mask (at 0, 5, and 10 cm H2O, and after a return to 0
      cm H2O) were studied in nine patients with acute left heart failure (pulmonary
      artery occlusion pressure [PAOP] > or = 18 mm Hg, and cardiac index [CI] < or =
      2.8 L/min/m2). CPAP at 10 cm H2O induced an improvement in lung compliance (60 +/
      10 ml/cm H2O to 87 +/- 20 ml/cm H2O, p < 0.05) and in lung and airway resistance
      (5.7 +/- 1.0 cm H2O/L/s to 3.4 +/- 1.0 cm H2O/L/s, p < 0.05), a reduction in work
      of breathing (18 +/- 3 J/min to 12 +/- 2 J/min, p < 0.05), and in the pressure
      time index of the respiratory muscles (279 +/- 22 cm H2O/s/min to 174 +/- 25 cm
      H2O/s/min, p < 0.05), without significant changes in breathing pattern. Despite a
      significant reduction in the negative swings in intrathoracic pressure (15.2 +/-
      1.9 cm H2O to 10.8 +/- 1.8 cm H2O, p < 0.001), no significant change was observed
      in CI or stroke volume during CPAP. However, mean transmural filling pressures
      decreased significantly with CPAP, suggesting a better cardiac performance.
      Neither the level of stroke volume nor of PAOP, was predictive of changes in CI
      or in stroke volume. In patients with respiratory insufficiency caused by
      congestive heart failure (CHF), CPAP reduces respiratory muscle effort without
      altering cardiac output. The slight decrease in mean transmural left and right
      atrial pressures suggests an improvement in cardiac performance.

PMID- 9032186
TI  - Beta-adrenergic agonist stimulated alveolar fluid clearance in ex vivo human and
      rat lungs.
AB  - Because beta-adrenergic agonist therapy may be useful clinically as a treatment
      to hasten the resolution of alveolar edema, this study was designed to examine
      the dose-dependent effects of beta-adrenergic agonist therapy on alveolar
      epithelial fluid clearance. The studies were done by instilling an isosmolar 5%
      albumin solution into the distal air spaces of both ex vivo rat and ex vivo human
      lungs that were inflated with 8 to 10 cm H2O with 100% oxygen and placed in a 37
      degrees C humid incubator. Alveolar fluid clearance was measured by the
      progressive increase in concentration of protein over 1 or 4 h. Salmeterol, a new
      long-acting lipophilic agent, was more potent than terbutaline in stimulating
      alveolar fluid clearance from the ex vivo human lung. Therefore, salmeterol was
      used for these studies. The results indicated that: (1) basal, unstimulated
      alveolar fluid clearance in rat lungs was significantly faster than in human
      lungs (24 +/- 4% over 4 h in rat lungs compared with 11 +/- 2% over 4 h in human
      lungs, p < 0.05); (2) comparison of equivalent doses of beta-adrenergic
      stimulation indicated that stimulated clearance rates were also faster in rat
      lungs than in human lungs; (3) very low doses of salmeterol were effective in ex
      vivo rat lungs (10(-8) M); and (4) relatively low doses were effective in the ex
      vivo human lungs (10(-6) M) as a treatment for increasing alveolar fluid
      clearance. In summary, there are significant differences in the basal and
      stimulated rates of alveolar epithelial fluid clearance in rat and human lungs,
      although the ex vivo human studies may have underestimated maximal alveolar fluid
      clearance in the intact human lung. The human lung responds well to relatively
      low doses of beta-adrenergic agonist therapy, a finding with potentially
      important clinical implications for hastening the resolution of alveolar edema.

PMID- 9032187
TI  - Impact of arachidonic versus eicosapentaenoic acid on exotonin-induced lung
      vascular leakage: relation to 4-series versus 5-series leukotriene generation.
AB  - Escherichia coli hemolysin (HlyA) is a proteinaceous pore-forming exotoxin that
      is implicated as a significant pathogenicity factor in extraintestinal E. coli
      infections including sepsis. In perfused rabbit lungs, subcytolytic
      concentrations of the toxin evoke thromboxane-mediated vasoconstriction and
      prostanoid-independent protracted vascular permeability increase (11). In the
      present study, the influence of submicromolar concentrations of free arachidonic
      acid (AA) and eicosapentaenoic acid (EPA) on the HlyA-induced leakage response
      was investigated. HlyA at concentration from 0.02 to 0.06 hemolytic units/ml
      provoked a dose-dependent, severalfold increase in the capillary filtration
      coefficient (Kfc), accompanied by the release of leukotriene(LT)B4, LTC4, and
      LTE4 into the recirculating buffer fluid. Simultaneous application of 100 nmol/L
      AA markedly augmented the HlyA-elicited leakage response, concomitant with an
      amplification of LTB4 release and a change in the kinetics of cysteinyl-LT
      generation. In contrast, 50 to 200 nmol/L EPA suppressed in a dose-dependent
      manner the HlyA-induced increase in Kfc values. This was accompanied by a
      blockage of 4-series LT generation and a dose-dependent appearance of LTB5, LTC5,
      and LTE5. In addition, EPA fully antagonized the AA-induced amplification of the
      HlyA-provoked Kfc increase, again accompanied by a shift from 4-series to 5
      series LT generation. We conclude that the vascular leakage provoked by HlyA in
      rabbit lungs is differentially influenced by free AA versus free EPA, related to
      the generation of 4- versus 5-series leukotrienes. The composition of lipid
      emulsions used for parenteral nutrition may thus influence inflammatory capillary
      leakage.

PMID- 9032188
TI  - Theoretical basis for improvement following reduction pneumoplasty in emphysema.
AB  - Reduction pneumoplasty may improve flow rates, comfort, and exercise tolerance in
      severe emphysema. The basis for improvement has not been systematically
      addressed. The major disability of emphysema stems from impairment of maximal
      expiratory flow-volume performance of the lung (MEFV). This requires the chest
      wall to operate at high volumes, which in turn severely compromises inspiratory
      muscle function. Clinical benefit, then, requires that MEFV performance improve
      so that the operating lung volume is reduced. This study presents theory and
      illustrative calculations. Removing nonventilating lung (e.g., bullae) simply
      displaces the MEFV curve down the volume axis. Removing ventilating parenchyma
      reduces both volume and maximal expiratory flow at iso-lung recoil pressure, and
      shortens the curve on the volume axis. The critical beneficial effect in both
      cases is reduction of the volume for a given limiting flow, VL (Vmax). Removing a
      given fraction of lung from the ventilating compartment is nearly as effective as
      removing it from the nonventilating compartment. Lowering of operating volumes
      benefits the strength, efficiency, endurance, and reserve of the inspiratory
      muscles and thus extends the metabolic scope of the emphysematous patient.

PMID- 9032189
TI  - Combined inhalation of nitric oxide and oxygen in chronic obstructive pulmonary
      disease.
AB  - Inhaled nitric oxide (NO) has been shown to reduce the mean pulmonary artery
      pressure (mPAP) and to improve PaO2 in patients with acute respiratory failure
      undergoing oxygen (O2) therapy. However, inhaled NO reduced pulmonary
      hypertension without improving PaO2 in patients with chronic obstructive
      pulmonary disease (COPD). This study was intended to compare the hemodynamic and
      gas exchange responses during inhalation of NO or O2 with those observed during
      the combined inhalation of NO and O2 in 10 spontaneously breathing COPD patients.
      Hemodynamic and blood gas parameters were measured after breathing: (1) room air;
      (2) NO added to room air; (3) O2 (1 L/min); or (4) NO and O2. During inhalation
      of 2 ppm NO added to room air, the mPAP (23.1 +/- 2.5 versus 20.6 +/- 2.2 mm Hg)
      and the pulmonary vascular resistance (PVR) (434 +/- 70 versus 378 +/- 50 dyne
      s/cm5) were significantly (p < 0.05) lower than those measured with room air.
      However, the values of PaO2 did not improve. The combined inhalation of NO and O2
      was associated not only with a significant (p < 0.05) decrease of mPAP (21.4 +/-
      2.3 versus 19.7 +/- 1.8 mm Hg) and PVR (431 +/- 72 versus 370 +/- 44 dyne s/cm5),
      but also with a remarkable improvement (p < 0.05) in the values of PaO2 (91.4 +/-
      6.6 versus 111.5 +/- 7.8 mm Hg) as compared with values obtained during the
      inhalation of O2 alone. These findings suggest that combined therapy with NO and
      O2 may constitute an alternative approach to treating patients with COPD and
      pulmonary hypertension.

PMID- 9032190
TI  - Factors contributing to relief of exertional breathlessness during hyperoxia in
      chronic airflow limitation.
AB  - The mechanisms of exertional dyspnea relief in response to supplemental oxygen
      (O2) in chronic airflow limitation (CAL) are not precisely known and are likely
      multifactorial. To explore factors contributing to the relief of dyspnea after
      oxygen administration, 11 patients with severe CAL (FEV1.0 = 39 +/- 3% predicted,
      mean +/- SEM) and mild hypoxemia (resting PaO2 = 74 +/- 2 mm Hg) breathed room
      air (RA) and 60% O2 during exercise at approximately 50% of their maximal
      incremental exercise capacity. Breathlessness ratings (Borg scale), endurance
      time, respiratory drive (change in mouth occlusion pressure over the first 0.1 s
      of inspiration, P0.1), ventilation (VE), breathing pattern, operational lung
      volumes, gas exchange, and metabolic parameters were compared during RA and 60%
      O2. PaO2 at exercise cessation during RA and 60% O2 was 65 +/- 3 mm Hg and 226 +/
      12 mm Hg, respectively (p < 0.001). With 60% O2, the mean of individual
      Borg/time slopes fell significantly (p < 0.05) by 23 +/- 12% and was associated
      with a 35 +/- 11% increase (p < 0.01) in endurance time (r = -0.64, p < 0.05).
      During 60% O2, slopes of P0.1 and lactate over time also fell significantly (p <
      0.05), whereas delta PaCO2/time did not change significantly. At a standardized
      time near end-exercise, Borg, VE, and P0.1 changed during 60% O2 by -0.8 +/- 0.3
      (p < 0.05), -4.1 +/- 2.0 L/min (p = 0.07), and -1.3 +/- 0.5 cm H2O/s (p < 0.05),
      respectively. Slopes of Borg/VE, Borg/lactate, and VE/lactate were essentially
      superimposable during tests on RA and O2: Borg, lactate, and VE all fell
      proportionally during hyperoxia. In patients with CAL and mild exercise
      hypoxemia, relief of exertional breathlessness during hyperoxia is explained by
      reduced ventilatory demand in association with reduced blood lactate levels.

PMID- 9032191
TI  - The intrapulmonary half-life and safety of aerosolized alpha1-protease inhibitor
      in normal volunteers.
AB  - Aerosol delivery of alpha1-protease-inhibitor (alpha1-PI) has the potential for
      reducing the amount of alpha1-PI needed to treat persons who are severely alpha1
      PI-deficient, thereby decreasing the high cost of treatment and making alpha1-PI
      available to treat many alpha1-PI-deficient persons who do not now have access to
      that product. Aerosolized alpha1-PI may also be useful in cystic fibrosis. The
      goal of our study was to evaluate the duration of action of aerosolized alpha1-PI
      and possible side effects in normal volunteers. Twenty-nine volunteers underwent
      bronchoalveolar lavage (BAL) and 3 to 7 d later inhaled 200 mg of alpha1-PI.
      Subjects were subsequently assigned to one of five groups; a second BAL was
      performed 0.5, 6, 12, 24, or 36 h after the aerosol, respectively. The BAL fluid
      samples were analyzed for alpha1-PI concentrations, anti-neutrophil elastase (NE)
      activity, cell count and differential, alpha1-PI-NE complex level, and uptake of
      alpha1-PI by alveolar macrophages. Overall we observed no substantial side
      effects. The one-time alpha1-PI aerosol induced a significant increase of alpha1
      PI concentrations as well as anti-NE activity. Even in the BAL fluid samples
      obtained 36 h after aerosol administration alpha1-PI concentrations and anti-NE
      activity were about double baseline values. The half-time in the lungs for alpha1
      PI concentrations and anti-NE activity were about double baseline values. The
      half-time in the lungs for alpha1-PI was 69.2 h and for anti-NE activity was 53.2
      h, respectively. We conclude from our data in normal volunteers that inhalation
      of aerosolized alpha1-PI may be a safe, effective, and conveniently administered
      therapy for persons with severe alpha1-PI deficiency; this mode of administration
      warrants further study.

PMID- 9032192
TI  - Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and
      COPD.
AB  - The role of glucocorticoids in the treatment of chronic obstructive pulmonary
      disease (COPD) is controversial. We have previously described high numbers of
      neutrophils and high concentrations of the inflammatory cytokines interleukin-8
      (IL-8) and tumor necrosis factor-alpha (TNF-alpha), and of the cell activation
      markers eosinophil cationic protein (ECP), eosinophil peroxidase (EPO),
      myeloperoxidase (MPO), and human neutrophil lipocalin (HNL) in COPD patients as
      compared with controls, and have postulated that the cytokines TNF-alpha and IL-8
      play a role in propagating the inflammatory response in COPD. We have now studied
      the effects of inhaled and oral glucocorticoids on these inflammatory indices in
      induced sputum. Initially, we studied the effect of a 2-wk course of inhaled
      budesonide (800 mg twice daily for 2 wk) in 13 patients with severe COPD (mean
      FDV1: 35% predicted). There was no clinical benefit in either lung function or
      symptom scores, and no significant change in the inflammatory indices as measured
      by total and differential cell counts and concentrations of TNF-alpha eosinophil
      activation markers ECP and EPO, and neutrophil activation markers MPO and HNL.
      Because the lack of anti-inflammatory effect might have been due to poor drug
      delivery as a result of severe airflow limitation, we undertook a study examining
      the antiinflammatory effect of oral prednisolone (30 mg daily for 2 wk) in
      patients with COPD and undertook the same measurements in 10 patients with atopic
      asthma. Sputum eosinophil numbers, ECP, and EPO were significantly reduced in the
      asthmatic patients but were not modified in COPD. This confirms the clinical
      impression that inhaled steroids have little antiinflammatory effect, at least in
      the short term in this group of patients, and suggests that the inflammatory
      process in COPD is resistant to the antiinflammatory effect of glucocorticoids.

PMID- 9032193
TI  - Total free living energy expenditure in patients with severe chronic obstructive
      pulmonary disease.
AB  - Resting energy expenditure (REE) is often elevated in patients with chronic
      obstructive pulmonary disease (COPD), but no data are available regarding total
      energy expenditure in free living conditions. We compared total daily energy
      expenditure (TDE) in eight COPD patients (FEV1 36 +/- 13%) admitted to a
      pulmonary rehabilitation center and eight independently living healthy subjects,
      matched for sex, age, and body mass index (BMI). TDE was measured over a 2-wk
      interval using doubly labeled water in combination with measurement of REE and
      body composition. The COPD patients had a significantly higher TDE than the
      healthy subjects (2,499 +/- 320 kcal/d and 2,107 +/- 88 kcal/d, respectively, p <
      0.01). The nonresting component of TDE (TDE-REE: physical activity and diet
      induced thermogenesis [DIT]) was significantly higher in the COPD patients than
      in the healthy subjects, resulting in a ratio between TDE and REE of 1.7 +/- 0.2
      and 1.4 +/- 0.1, respectively (p < 0.01). The results indicate that COPD patients
      exhibit an increased TDE in comparison with healthy subjects. The difference
      could by attributed to an increase in the nonresting component of TDE, since REE
      was comparable between the groups.

PMID- 9032194
TI  - Intensity of training and physiologic adaptation in patients with chronic
      obstructive pulmonary disease.
AB  - The applicability of high-intensity training and the possibility of inducing
      physiologic adaptation to training are still uncertain in patients with severe
      chronic obstructive pulmonary disease (COPD). The purposes of this study were to
      evaluate the proportion of patients with moderate to severe COPD in whom high
      intensity exercise training (30-min exercise session at 80% of baseline maximal
      power output [Wmax]) is feasible, and the response to training in these patients.
      We also sought to evaluate the possible influence of disease severity on the
      training intensity achieved and on the development of physiologic adaptation
      following endurance training. Forty-two patients with COPD (age = 66 +/- 7 yr,
      FEV1 = 38 +/- 13% predicted, [mean +/- SD]) were evaluated at baseline and after
      a 12-wk endurance training program. Each evaluation included a stepwise exercise
      test on an ergocycle up to the individual maximal capacity during which minute
      ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), and
      arterial lactic acid concentrations were measured. The training consisted of 25
      to 30-min exercise sessions on a calibrated ergocycle three times a week, with a
      target training intensity at 80% of Wmax. The training intensity was adjusted
      with the objective of reaching the target intensity, but also to ensure that the
      cycling exercise could be maintained for the specified duration. The training
      intensity sustained for the duration of each exercise session averaged 24.5 +/-
      12.6, 51.7 +/- 17.4, 63.8 +/- 22.4, and 60.4 +/- 22.7% of Wmax at Weeks 2, 4, 10,
      and 12, respectively. High-intensity training was achieved in zero, three, five,
      and five patients at Weeks 2, 4, 10, and 12, respectively. A significant increase
      in VO2max and Wmax occurred with training (p < 0.0002). This improvement in
      exercise capacity was accompanied by a 6% and 17% reduction in VE and in arterial
      lactic acid concentration for a given work rate, respectively (p < 0.0001),
      suggesting that physiologic adaptation to training occurred. The intensity of
      training achieved, in % Wmax, was not influenced by the initial VO2max, age, or
      FEV1. The effects of training were compared in patients with an FEV1 > or = 40%
      or < 40% predicted. Percent changes in VO2max, Wmax, and VE, were significant and
      of similar magnitude for both groups, whereas the decrease in arterial lactic
      acid for a given work rate reached statistical significance only in those
      patients with an FEV1 > or = 40% predicted. We conclude that although most
      patients were unable to achieve high-intensity training as defined in this study,
      significant improvement in their exercise capacity was obtained and physiologic
      adaptation to endurance training occurred. The training intensity expressed as a
      percent of the individual maximum exercise capacity, and the relative
      effectiveness of training, were not influenced by the severity of airflow
      obstruction.

PMID- 9032195
TI  - Respiratory allergy to rats: exposure-response relationships in laboratory animal
      workers.
AB  - Laboratory animal workers are at high risk of developing occupational allergy.
      Little is known about the relationship between levels of exposure and the risk of
      developing laboratory animal allergy. A cross-sectional study was performed in
      540 workers at eight facilities to quantify the exposure-response relationship
      for allergy to rats, while controlling for determinants like atopy, gender, and
      smoking. All participants completed a questionnaire, underwent skin prick testing
      with common and occupational allergens, and total IgE as well as occupational
      allergen-specific IgE antibodies were serologically measured. Personal air dust
      samples were taken during full-shift periods to estimate the rat urinary
      aeroallergen exposure levels. In the whole study population no clear exposure
      response relationship was observed. However, in the group of workers with less
      than 4 yr of working experience with laboratory animals the prevalence rate of
      sensitization to rat allergens was clearly associated with exposure levels. The
      exposure-response relationship was steepest for workers with atopy-associated
      risk factors, i.e., self-reported allergy or sensitization to cats or dogs, or
      elevated total serum IgE. The prevalence rates of sensitization to rat allergens
      for these workers were about 15, 9.5, and 7.3 times higher in the high, medium,
      and low exposure group, respectively, compared with internal reference group.

PMID- 9032196
TI  - Effects of air pollution on emergency room visits for respiratory illnesses in
      Montreal, Quebec.
AB  - As an approach to evaluating the public health burden from current air pollution
      levels, we examined the relationship of daily emergency room (ER) visits for
      respiratory illnesses (25 hospitals, average 98 visits/d) to air pollution in
      Montreal, Canada, from June through September, 1992 and 1993. Air pollutants
      measured included ozone (O3), particulate matter diameter < 10 microm (PM10) and
      < 2.5 microm (PM2.5), the sulfate fraction of PM2.5 (SO4), and aerosol strong
      acidity (H+). Temporal trends, autocorrelation, and weather were controlled for
      in time-series regressions. For 1992, no significant associations with ER visits
      were found. However, 33% of the particulate data were missing. For 1993, 1-h
      maximum O3, PM10, PM2.5, and SO4 were all positively associated with respiratory
      visits for patients over 64 yr of age (p < 0.02). An increase to the mean level
      of 1-h maximum O3 (36 ppb) was associated with a 21% increase over the mean
      number of daily ER visits (95% confidence interval [CI]: 8 to 34%). Effects of
      particulates were smaller, with mean increases of 16% (4 to 28%), 12% (2 to 21%)
      and 6% (1 to 12%) for PM10, PM2.5, and SO4, respectively. Relative mass effects
      were PM2.5 > PM10 >> SO4. Ozone and PM10 levels never exceeded 67 ppb and 51
      microg/m3, respectively (well below the U.S. National Ambient Air Quality
      Standards of 120 ppb and 150 microg/m3, respectively). The present findings have
      public health implications with regard to the adverse health effects of urban
      photochemical air pollution on older individuals.

PMID- 9032197
TI  - Perceived control of asthma: development and validation of a questionnaire.
AB  - Psychological factors can play a role in asthma symptoms and may play a role in
      how individuals manage asthma. Because poor self-management of asthma has been
      linked to poor outcomes, it is important to understand perceived control of
      asthma--the individual's perceived ability to deal with asthma and its
      exacerbations effectively. This study used data from an ongoing panel study of
      adults with asthma (n = 601). The 11-item Perceived Control of Asthma
      Questionnaire (PCAQ) demonstrated internal consistency (Cronbach's alpha = 0.74)
      and excellent construct validity, correlating strongly with asthma severity,
      quality of life, and Medical Outcomes Study Short Form (SF-36) measures of health
      status (p < 0.05). After controlling for demographics and asthma severity, each 6
      point decrement in PCAQ score was significantly associated with increased risk of
      hospitalization (OR = 1.4 [95% CI: 1.1 to 1.8]), frequent activity restriction
      (OR = 1.5 [1.2 to 1.8]), and, among those with labor force participation (n =
      551), asthma-related cessation of employment (OR = 1.7 [1.1 to 2.4]). The PCAQ is
      a short, easy to administer, reliable, and valid measure of perceived control of
      asthma. It is strongly associated with adverse asthma outcomes even taking into
      account demographic characteristics and asthma severity, suggesting that patient
      centered interventions focusing on perceived control might improve asthma
      outcomes.

PMID- 9032198
TI  - Directly observed isoniazid preventive therapy for released jail inmates.
AB  - This study was designed to determine whether an integrated screening program
      could be implemented that identified persons with latent tuberculosis infection
      among jail inmates and produced a high rate of completion of isoniazid preventive
      therapy (IPT) in those persons after their discharge from short-term detention,
      by means of community-based directly observed preventive therapy (DOPT). From
      June 1, 1992 through December 31, 1994 inmates in the King County Jail who were
      from populations at high risk of tuberculosis were screened by means of the
      tuberculin skin test and those with latent tuberculosis infection were offered
      IPT. Among 262 inmates receiving IPT upon release from jail, 105 (40%) could not
      be located after release. Among another 105 enrolled on DOPT, 63 (60%) completed
      therapy. Among 52 who chose self-supervised isoniazid therapy after release, 15
      (29%) completed therapy (chi-square = 13.50, p = 0.0002). Among persons with
      latent tuberculosis infection detected during screening at a county jail, a
      postrelease DOPT program resulted in a high rate of immediate loss to follow-up
      and a low rate of completion of therapy. Based on these results, we suggest that
      funds for TB control, if limited, should not be diverted to jail-based screening
      and postrelease DOPT.

PMID- 9032199
TI  - Selection of T lymphocytes bearing limited TCR-Vbeta regions in the lung of
      hypersensitivity pneumonitis and sarcoidosis.
AB  - Hypersensitivity pneumonitis (HP) and sarcoidosis are interstitial lung disorders
      (ILD) characterized by a lymphocytic alveolitis that, in the active phase of the
      disease, is sustained by different T-cell subsets, i.e., CD8+ cells in HP and
      CD4+ lymphocytes in sarcoid patients. To address the question of whether a bias
      in T-cell selection occurs in the lung of patients with HP and sarcoidosis, we
      analyzed the T-cell receptor beta chain variable region (TCR-Vbeta) repertoire by
      flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung
      lymphocytes of 14 HP and 25 sarcoid patients. To verify whether these cells can
      be activated in vitro through the TCR, blood and lung lymphocytes were also
      assessed for their responsiveness to different superantigenic stimuli represented
      by staphylococcal enterotoxins, including SEA, SEB, SEC1, SEC2, SED, and SEE.
      Flow cytometry and PCR analyses demonstrated an overexpression of cells bearing
      Vbeta2, Vbeta3, Vbeta5, Vbeta6, and Vbeta8 gene segments in the lung of HP
      patients as compared with the peripheral blood. In sarcoid patients cells bearing
      Vbeta2, Vbeta5, and Vbeta6 gene segments in the lung of HP patients as compared
      with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and
      Vbeta6 gene segments were overrepresented in the lung rather than in the blood.
      Both in HP and sarcoid patients almost all T cells bearing the dominant Vbeta
      segment belonged to the T-cell subset that sustains the alveolitis, i.e., CD8 in
      HP patients and CD4 in sarcoid subjects. Follow-up studies demonstrated that the
      recovery of the alveolitis was characterized by the disappearance of cells
      bearing a limited T-cell repertoire. Interestingly, T-lymphocyte response to
      different superantigens demonstrated that the proliferation elicited by different
      staphylococcal toxins was more pronounced in the lung than in the blood. Taken
      together, our findings indicate a compartmentalization of cells bearing discrete
      Vbeta gene products in the pulmonary microenvironment and suggest that the
      expansion of specific Vbeta region subsets occurring in the lung might result
      from triggering by a specific antigen. In fact, the removal from exposure in HP
      patients or specific treatment in sarcoidosis resulted in the decrease of the
      overrepresented cell population accounting for the lymphocytic alveolitis.

PMID- 9032201
TI  - Passive immunization against tumor necrosis factor-alpha impairs host defense
      during pneumococcal pneumonia in mice.
AB  - Streptococcus pneumoniae is the most frequent cause of community-acquired
      pneumonia. We sought to determine the role of tumor necrosis factor-alpha (TNF)
      in the pathogenesis of pneumococcal pneumonia. Induction of pneumonia in C57B1/6
      mice by intranasal inoculation with 10(6) colony-forming units (cfu) S.
      pneumoniae resulted in a sustained increase in TNF activity in lung homogenates
      reaching a plateau between 12 and 72 h (72 h: 185.49 +/- 54.41 ng/g), while
      plasma TNF activity remained low or undetectable. Treatment with a neutralizing
      anti-TNF monoclonal antibody 2 h before inoculation strongly reduced lung TNF
      activity, but only modestly diminished lung interleukin (IL)-1beta levels, and
      did not significantly influence lung IL-6, IL-10, and interferon-gamma
      concentrations. Anti-TNF-treated mice had fourfold more S. pneumoniae cfu
      isolated from lungs than control mice 40 h after inoculation (p < 0.05), although
      lung myeloperoxidase activities were similar in both treatment groups. Anti-TNF
      treated mice died significantly earlier from pneumococcal pneumonia than control
      mice (p < 0.05). Endogenously produced TNF is important for host defense during
      pneumococcal pneumonia.

PMID- 9032202
TI  - O2-induced change in ventilation and ventilatory drive in COPD.
AB  - We examined the role of respiratory control during O2-induced hypercarbia in
      patients with chronic obstructive pulmonary disease (COPD), by comparing the
      observed change in ventilation (delta VEobs) with the delta VE predicted (delta
      VEpred) from the patients' ventilatory drive and the O2-induced delta PaCO2 and
      delta SaO2. Eleven stable hypoxemic COPD patients (mean +/- SD: FEV1 = 1.00 +/-
      0.25 L, FVC = 2.33 +/- 0.38 L; room air PaCO2 = 52.7 +/- 7.9 mm Hg, SaO2 87.7 +/-
      5.1%) were studied. Using standard rebreathing methods, we measured the
      ventilatory responses to hypercapnia (delta VE/PCO2 = 0.76 +/- 0.55 L/min/mm Hg)
      and to hypoxia (delta VE/delta SaO2 = -0.74 +/- 0.31 L/min/%). After breathing
      100% O2 for 15 min, the mean delta VEobs was -0.08 +/- 0.62 (SEM) L/min (p = NS),
      the delta SaO2 was 7.6 +/- 3.6% (p < 0.001), and the delta PaCO2 was 6.6 +/- 3.3
      mm Hg (p < 0.001). The delta VEpred was expressed as the sum of a decrease in
      ventilation due to suppression of hypoxic drive [calculated as the product (delta
      VE/SaO2) x delta SaO2] and an increase in ventilation due to the O2-induced
      hypercarbia [calculated as the production (delta VE/delta PCO2) x delta PaCO2].
      The mean delta VEpred [-0.96 +/- 0.68 (SEM)] did not differ significantly from
      mean delta VEobs. We conclude that the O2-induced delta VEobs is equal to that
      expected from the ventilatory drives and the changes in PaCO2 and SaO2; and that
      O2-induced hypercarbia does not indicate a failure of respiratory control
      mechanisms in the maintenance of PaCO2 homeostasis.

PMID- 9032200
TI  - Intracellular pH regulation in cultured human pleural mesothelial cells.
AB  - The human pleural space is lined by a single layer of mesothelial cells, the
      intracellular pH (pH(i)) of which has never been investigated. In the present
      study, the intrinsic buffering power of H+ ions (beta(i)) and the pH(i)
      regulatory systems were investigated in primary cultures of human pleural
      mesothelial cells (PMCs) with microspectrofluorimetry. We found: (1) that at the
      resting pH(i), the beta(i) was low and increased as the pH(i) decreased; (2) that
      the pH(i) recovery was largely inhibited either with Na+-free medium or nominally
      HCO3 free medium containing ethyl-isopropyl amiloride (EIPA); (3) a 4-4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive, Na+/HCO3
      dependent, but Cl(-)-independent acid extrusion mechanism in CO2/HCO3 buffer; and
      (4) that in the same buffer, a DIDS- sensitive but Na+-independent alkalosis was
      induced by intracellular Cl- depletion. We therefore conclude that at least three
      membrane pH(i) regulators are involved in regulating the pH(i) in PMCs, these
      being the EIPA-sensitive Na+-H+ exchanger; a novel electroneutral, DIDS-sensitive
      Na+-HCO3 cotransporter; and the DIDS-sensitive Cl(-)-HCO3 exchanger. Furthermore,
      under physiologic conditions, the Na+-HCO3 cotransporter plays a more important
      role in extrusion of excess intracellular H+ ions than does the Na+-H+ exchanger.

PMID- 9032203
TI  - Abnormal skeletal muscle oxidative capacity after lung transplantation by 31P
      MRS.
AB  - Although lung transplantation improves exercise capacity by removal of a
      ventilatory limitation, recipients' postoperative maximum oxygen uptake (VO2max)
      remains markedly abnormal. To determine if abnormal skeletal muscle oxidative
      capacity contributes to this impaired aerobic capacity, nine lung transplant
      recipients and eight healthy volunteers performed incremental quadriceps exercise
      to exhaustion with simultaneous measurements of pulmonary gas exchange, minute
      ventilation, blood lactate, and quadriceps muscle pH and phosphorylation
      potential by 31P-magnetic resonance spectroscopy (31P-MRS). Five to 38 mo after
      lung transplantation, peak VO2 was decreased compared with that of normal control
      subjects (6.7 +/- 0.4 versus 12.3 +/- 1.0 ml/min/kg, p < 0.001), even after
      accounting for differences in age and lean body weight. Neither ventilation,
      arterial O2 saturation nor mild anemia could account for the decrease in aerobic
      capacity. Quadriceps muscle intracellular pH (pH(i)) was more acidic at rest
      (7.07 +/- 0.01 versus 7.12 +/- 0.01 units, p < 0.05) and fell during exercise
      from baseline values at a lower metabolic rate (282 +/- 21 versus 577 +/- 52
      ml/min, p < 0.001). Regressions for pH(i) versus VO2, phosphocreatine/inorganic
      phosphate ratio (PCr/Pi) versus VO2, and blood lactate versus pH(i) were not
      different. Among transplant recipients, the metabolic rate at which pH(i) fell
      correlated closely with VO2max (r = 0.87, p < 0.01). The persistent decrease in
      VO2max after lung transplantation may be related to abnormalities of skeletal
      muscle oxidative capacity.

PMID- 9032205
TI  - Effects of angiotensin converting enzyme inhibition on crossbridge properties of
      diaphragm in cardiomyopathic hamsters of the dilated bio 53-58 strain.
AB  - Crossbridge properties of cardiomyopathic Syrian hamster (CSH) diaphragm from the
      dilated Bio 53-58 strain were analyzed after 5-mo of treatment with the
      angiotensin converting enzyme (ACE) inhibitor perindopril (1 mg/kg/d by oral
      gavage). Three groups were studied: control F1B hamsters (C; n = 14); CSH given
      placebo (PL; n = 11 ); and perindopril-treated CSH (PE; n = 11). Peak isometric
      tension was lower in PL than in C, in both twitch (21.4 +/- 1.5 versus 46.9 +/-
      1.5 mN/mm2; p < 0.001) and tetanus (41.0 +/- 2.7 versus 90.5 +/- 3.3 mN/mm2; p <
      0.001). In PE, peak isometric tension was intermediate between C and PL, and was
      significantly lower than in C and higher than in PL. The single force of one
      crossbridge (pi), the number (m) of crossbridges, the turnover rate of myosin
      adenosine triphosphatase (ATPase) (kcat), and peak mechanical efficiency (Effmax)
      were calculated from A.F. Huxley's equations; m was lower in PL than in C, in
      both twitch (3.4 +/- 0.2 versus 4.9 +/- 0.2 10(9)/mm2; p < 0.001) and tetanus
      (4.0 +/- 0.3 versus 8.9 +/- 0.7 10(9)/mm2; p < 0.001); m was higher in PE than in
      PL, in both twitch 4.3 +/- 0.5 versus 3.4 +/- 0.2 10(9)/mm2; NS) and tetanus (6.2
      +/- 0.4 versus 4.0 +/- 0.3 10(9)/mm2; p < 0.01), with no change in pi. In the
      three groups, Effmax correlated linearly with kcat (r = 0.93; p = 0.001) and
      showed a negative linear correlation with pi (r = 0.996; p = 0.001). In
      conclusion, our results show that in experimental cardiomyopathy, ACE inhibitor
      mainly helps to prevent a decrease in the number of diaphragm muscle
      crossbridges, resulting in preserved peak isometric tension.

PMID- 9032204
TI  - Effect of free radical scavengers on diaphragmatic fatigue.
AB  - Recent studies have suggested that free radical scavenger administration reduces
      the rate of development of diaphragm fatigue. Much of this work has been done,
      however, using in vitro muscle preparations; the purpose of the present study was
      to assess the effect of scavengers on in vivo diaphragm contractile function. To
      accomplish this, we compared the rate of development of fatigue of the
      electrically stimulated diaphragm in four groups of dogs: (1) animals given
      intravenous polyethylene glycol adsorbed superoxide dismutase (PEG-SOD, 2,000
      units/kg) 1 h before a fatigue trial; (2) a group given intravenous
      dimethylsulfoxide (DMSO, 0.5 ml/kg of a 50% solution) before fatigue; (3) a group
      given saline before fatigue; and (4) a group treated with denatured PEG-SOD
      (2,000 units/kg) before fatigue. We measured diaphragmatic concentrations of
      thiobarbituric acid reactive substances (TBAR), a marker of free radical-mediated
      lipid peroxidation, on muscle samples taken at the conclusion of fatigue trials.
      As a control, we also measured TBAR concentrations for muscle samples taken from
      nonfatigued diaphragm. We found that the rate of development of diaphragm fatigue
      was much greater in saline and denatured PEG-SOD-treated groups than for animals
      pretreated with either PEG-SOD or DMSO, with force falling to 23 +/- 4, 21 +/- 4,
      50 +/- 7, and 47 +/- 6% of its initial value, respectively, over a 2-h period of
      electrophrenic stimulation in these four groups of animals (p < 0.01). TBAR
      concentrations in fatigued diaphragm from saline and denatured PEG-SOD-treated
      animals were significantly higher than levels for either nonfatigued fresh
      diaphragm or fatigued diaphragm taken from PEG-SOD- or DMSO-treated animals (p <
      0.01). These data suggest that diaphragm fatigue resulting from repetitive low
      frequency stimulation is associated with lipid peroxidation within this muscle
      and that pretreatment with free radical scavengers prevents lipid peroxidation
      and reduces the rate of development of fatigue.

PMID- 9032206
TI  - Activation of intrinsic laryngeal muscles during cough.
AB  - We studied the pattern of discharge of the posterior cricoarytenoid (PCA),
      cricothyroid (CT), thyroarytenoid (TA), and arytenoideus transversus (AR) muscles
      during cough in 12 anesthetized dogs. Diaphragm electromyographic (EMG) activity
      was also recorded, together with subglottic and esophageal pressures. Trains of
      repetitive coughs were induced by mechanically stimulating the tracheobronchial
      airway. Trials with the upper airway isolated from and connected to the lower
      airway were performed before and following bilateral sectioning of the internal
      branch of the superior laryngeal nerve (SLN). The immediate effect of tracheal
      stimulation was an "apneic" period at FRC, during which the PCA, a laryngeal
      abductor, showed a progressive increase in activity accompanied by small,
      variable increases in the activity of the CT and the laryngeal adductors, the TA
      and AR. The subsequent cough efforts were divided into three phases: inspiration,
      glottic narrowing, and forced expiration. PCA activity was greatest during the
      inspiratory phase and CT activity was greatest during the expiratory phase. Peak
      subglottic pressure occurred during glottic narrowing and coincided with the
      greatest activation of the TA and AR during the cough effort, and suppression of
      the PCA and CT. The patterns of EMG activation were not affected by the route of
      breathing or SLN section. The results suggest the presence of a uniquely central
      process controlling laryngeal muscles during cough, independent of laryngeal
      sensory feedback.

PMID- 9032207
TI  - Diaphragm performance during maximal voluntary ventilation in chronic obstructive
      pulmonary disease.
AB  - In normal subjects 2 min of maximal voluntary hyperventilation results in failure
      of tension generation and low-frequency fatigue of the diaphragm. Patients with
      severe chronic obstructive pulmonary disease (COPD) do not develop diaphragm
      fatigue during exhaustive treadmill exercise despite excessive inspiratory muscle
      loading and we hypothesized that they might be relatively resistant to the
      development of diaphragm fatigue during maximal ventilation. In six patients with
      severe COPD (mean FEV1 0.671) we therefore loaded the diaphragm using 2 min of
      maximal isocapnic ventilation (MIV). Initial mean ventilation was 28.6 L/min and
      diaphragm pressure-time product (PTPdi) 602 cm H2O x s/min; these values were
      sustained throughout MIV without significant decline. Mean twitch
      transdiaphragmatic pressure (Tw Pdi) was 19.7 cm H2O 25 min after a control run
      and 20.5 cm H2O at the same time after MIV [corrected]. Compared with normal
      subjects previously studied in our laboratory (Hamnegard, C.-H., et al. Eur.
      Respir. J. 1996;9:241-247) the reduction in PTPdi was disproportionately greater
      than the reduction in Tw Pdi. We conclude that, unlike normal subjects, 2 min of
      MIV causes neither failure of diaphragm performance nor low-frequency diaphragm
      fatigue in patients with severe COPD. It is likely that the diaphragm makes a
      relatively limited contribution to the generation of maximal levels of
      ventilation in severe COPD.

PMID- 9032208
TI  - Determinants of lung volume in spontaneously breathing preterm infants.
AB  - To study the effects of apneic pauses, sighs, and breathing patterns on
      functional residual capacity (FRC), we measured FRC repeatedly in 48 healthy
      preterm infants (weight at study 2,042 +/- 316 g [mean +/- SD], postconceptional
      age 36.6 +/- 2.0 wk), during unsedated sleep using a modified heliox/nitrogen
      washout technique. Breathing movements and pulse oximeter saturation (SpO2) were
      recorded throughout and recordings analyzed for the presence of regular and
      nonregular breathing pattern, apneic pauses, sighs, and desaturations (SpO2 <
      90%) during the last 2 min prior to each FRC measurement. FRC was lower during
      nonregular than during regular breathing pattern (23.3 +/- 7.2 ml/kg versus 26.9
      +/- 7.8 ml/kg, p < 0.02); however, this apparent effect of breathing pattern
      disappeared after controlling the data for apneic pauses. Apneic pauses resulted
      in a significant decrease in FRC: mean FRC was 20.0 +/- 6.8 ml/kg if measured
      within 2 min of an apneic pause, 26.0 +/- 6.9 ml/kg if measured after a sigh (p <
      0.001), and 24.0 +/- 7.7 ml/kg if there had been neither a sigh nor an apneic
      pause (p < 0.05). The interval between the apneic pause and the FRC measurement
      had no effect on FRC. There was an inverse correlation between FRC and the speed
      with which SpO2 fell during desaturation (r = -O.5, p < 0.03). Apneic pauses
      resulted in a persistent reduction in FRC in these preterm infants. Sighs
      appeared to restore FRC. The significant relationship between FRC and the speed
      of desaturation found in this study underscores the importance of endogenous or
      exogenous strategies that help to increase FRC, such as sighs or the application
      of continuous positive airway pressure, for the stability of oxygenation in
      preterm infants who have difficulty maintaining their oxygenation.

PMID- 9032209
TI  - Summertime haze air pollution and children with asthma.
AB  - In order to investigate associations between summertime haze air pollution and
      asthma at an individual level, 52, 58, and 56 children (ages 7 to 13) attending a
      summer "asthma camp" were followed during the last week of June in 1991, 1992,
      and 1993, respectively. Most of the subjects had moderate to severe asthma. Daily
      records were kept of the environmental conditions, as well as of subject
      medication use, lung function, and medical symptoms. Air pollution was found to
      be significantly and consistently correlated with acute asthma exacerbations,
      chest symptoms, and lung function decrements. The pollutant most consistently
      associated with adverse health consequences was ozone (O3), although associations
      with sulfates and hydrogen ion suggest a possible role by fine particles as well.
      Effects were found to be roughly monotonic as a function of O3 concentration.
      Regression of morning (8:00 A.M.) to afternoon (5:00 P.M.) peak flow change on O3
      indicated pulmonary function reductions similar to those previously reported for
      more active children without asthma. Moreover, analyses also indicated an
      increased risk of an asthma exacerbation and of experiencing chest symptoms of
      approximately 40% on the highest pollution day, relative to the mean. Based on
      these relative risk estimates, a rise in the 1-h daily maximal O3 from 84 ppb to
      160 ppb was associated in this group with an increase from 20 to 28 (+/- 2) in
      the expected number of unscheduled medications administered/day, and from 29 to
      41 (+/- 3) in the expected total number of chest symptoms/day. Thus, air
      pollution can be a major contributor to the respiratory problems experienced by
      children with asthma during the summer months.

PMID- 9032210
TI  - Influence of the route of allergen administration and genetic background on the
      murine allergic pulmonary response.
AB  - We used various ovalbumin sensitization and challenge protocols to determine the
      importance of the route of allergen administration and the genetic background in
      modulating the physiologic, inflammatory, and immunologic features characteristic
      of allergen-induced asthma. In BALB/c mice, induction of maximal airway
      hyperresponsiveness and airspace eosinophilia required administration of
      ovalbumin by both the intraperitoneal and the intranasal routes (combination
      protocol), whereas intraperitoneal immunization alone resulted in maximal
      ovalbumin-specific IgE plasma levels. Thus, a systemic immune response to
      allergen, in addition to, or independent of IgE production, as well as local
      allergen challenge were necessary for maximal induction of pulmonary disease.
      BALB/c mice treated with ovalbumin by the combination protocol had increased Th2
      type cytokine mRNA levels in bronchial lymph node tissue compared with control
      mice. In contrast, C57BL/6 mice treated with ovalbumin by the combination
      protocol had significantly decreased responses compared with BALB/c mice for all
      parameters of allergic pulmonary disease examined, with the exception of airspace
      eosinophilia. Genetic background has a striking and selective effect on the
      phenotype of murine allergic pulmonary disease. Further analysis of this murine
      model should be useful in helping define the critical pathogenetic events in
      allergen-induced asthma.

PMID- 9032211
TI  - Prostaglandin H synthase 1 and 2 immunoreactivities in the bronchial mucosa of
      asthmatics.
AB  - Prostaglandin H synthases or cyclooxygenases 1 (PGHS-1) and 2 (PGHS-2) catalyze
      the conversion of arachidonic acid to prostaglandin endoperoxides, leading to the
      formation of prostaglandin and thromboxane mediators of inflammation. The
      expression of these enzymes in the respiratory epithelium has not been
      determined, although they may be relevant to the pathophysiology of inflammatory
      disorders such as asthma and chronic bronchitis (CB). We studied PGHS-1 and PGHS
      2 immunoreactivity in bronchial biopsies obtained from 22 patients with chronic
      stable asthma, seven patients with CB, and 12 normal subjects. Both types of PGHS
      were mainly expressed in the epithelium (basal and ciliated cells), and PGHS-1
      and PGHS-2 were found in 21 of 41 and 34 of 41 biopsies, respectively. We did not
      find any differences in PGHS expression between the patient populations. There
      were no correlations between any of the clinical parameters studied or the
      pathologic patterns and the presence and characteristics of the PGHS
      immunoreactivities. Thus, both PGHS enzymes are expressed in normal human
      respiratory epithelium and are not quantitatively upregulated in the main bronchi
      in stable asthma and CB.

PMID- 9032212
TI  - Platelet-derived growth factor in bronchiolitis obliterans-organizing pneumonia.
AB  - Bronchiolitis obliterans-organizing pneumonia (BOOP) is a disorder characterized
      by intraluminal proliferation of connective tissue in distal air spaces. As part
      of a general investigation of the role of growth factors in this process, the
      present study examined the expression of the mitogen, platelet-derived growth
      factor (PDGF), and one of its receptors, PDGFR-beta, in this disease. Serial
      sections of lung biopsy specimens from 20 patients with BOOP and 10 control
      subjects were stained with antibodies against PDGF, PDGFR-beta, and the
      monocyte/macrophage marker CD68. Stereologic point counting showed that PDGF+
      cells represented 4.6 +/- 1.6% (mean +/- SD) of the volume occupied by lung
      tissue in BOOP and 2.1 +/- 0.7% in the control subjects (p < 0.0001). In both
      groups the positive cells were tissue macrophages, and CD68+ macrophages
      accounted for 10.7 +/- 4.7% of the lung tissue in BOOP as compared with 5.4 +/-
      3.7% in the control subjects (p < 0.005). PDGFR-beta immunoreactivity was present
      in some alveolar epithelial cells in BOOP, but was absent in control subjects. We
      conclude that PDGF+ cells and CD68+ macrophages are found in greater numbers in
      lungs with BOOP, and an increased expression of PDGFR-beta epitopes was observed
      in some patients with BOOP. We speculate that these molecules are important in
      the pathogenesis of the destructive fibroproliferative process that characterizes
      this disease.

PMID- 9032213
TI  - Airway closure measured by a technegas bolus and SPECT.
AB  - Absence of a maximal dose-response plateau and mathematical modeling suggest that
      asthmatic airways close during bronchoconstriction. Finding segmental areas
      affected by closure would be important in understanding asthmatic airway
      function. The aim of this study was to evaluate single-photon emission computed
      tomography (SPECT) as a method of investigating airway closure. Simultaneous
      SPECT transmission and emission studies were performed on a thoracic phantom to
      develop analysis methodology, and on 13 normal subjects after they inhaled a
      Technegas bolus from residual volume (RV), to measure airway closure. Single
      breath nitrogen test values and lung volumes were measured. Airway closure was
      defined as the percent of Technegas-free lung volume (LVclosed). The mean error
      +/- 95% CI of the error, as determined by transmission scan, was 1.1 ml +/- 165
      ml (0.8% +/- 15% lung volume) in the phantom studies, and 112 ml +/- 419 ml (4%
      +/- 31% of supine functional residual capacity [FRC]) in the human studies.
      LVclosed correlated with closing capacity (r = 0.86, p < 0.01 ) and closing
      volume (r = 0.86, p < 0.01), but not with RV/total lung capacity (TLC). This
      study indicates that simultaneous SPECT emission and transmission scans, using a
      Technegas bolus, are a valid method of measuring airway closure in vivo, with the
      added advantage of providing three-dimensional data that allow the detection of
      small, discrete areas of airway closure and determination of their volumes and
      shapes.

PMID- 9032214
TI  - Bronchial blood vessel dimensions in asthma.
AB  - The extent to which the bronchial vasculature contributes to airway wall
      thickening in large and small airways in patients with asthma is unknown. The aim
      of this study was to quantify the number and the area occupied by blood vessels
      in the airway submucosa of patients with and without asthma. We used the
      monoclonal antibody Factor VIII to measure the blood vessels between the airway
      basement membrane and the outer border of the smooth muscle. In large
      cartilaginous airways in patients with fatal asthma, the number and area of large
      blood vessels were increased and the number and area of small blood vessels were
      decreased, compared with that in patients with nonfatal asthma and control
      subjects. However, the total number of blood vessels and the total area occupied
      by blood vessels per square millimeter in the airway submucosa were similar in
      patients with fatal asthma or nonfatal asthma and in control subjects in all
      airway size groups. Blood vessels were distended to a mean value of 80% of their
      estimated maximal area. The increased number of larger vessels in patients with
      fatal asthma raises the possibility that vascular congestion associated with an
      acute severe asthma attack may distend blood vessels. The finding of similar
      numbers of blood vessels per square millimeter of submucosa in control subjects
      and in patients with asthma suggests that blood vessels increase in number in
      patients with asthma only in proportion to increased airway wall area. It is
      unlikely that submucosal vessels could act as capacitance vessels and
      significantly alter inner airway wall thickness.

PMID- 9032215
TI  - RANTES in human allergen-induced rhinitis: cellular source and relation to tissue
      eosinophilia.
AB  - Human allergen-induced rhinitis is associated with recruitment and activation of
      CD4+ T lymphocytes and eosinophils. RANTES is a novel CC chemokine that is a
      potent chemoattractant for both memory T cells and eosinophils. We therefore
      investigated RANTES in the nasal mucosa after local allergen provocation. Nasal
      lavage was performed, and biopsies from the inferior nasal turbinate were taken
      from 14 atopic, seasonal rhinitic patients and seven normal subjects for as long
      as 6 h after challenge with a grass pollen extract and after a control (allergen
      diluent) challenge. In five of seven rhinitics tested, radioimmunoassay of nasal
      fluid demonstrated increases in RANTES at 2 to 4 h (p < 0.05). Nasal allergen
      challenge provoked significant increases in RANTES mRNA (p = 0.0015) and protein
      (p = 0.01) containing cells in the nasal submucosa at 6 h. No changes were
      observed in normal subjects. Increases in RANTES mRNA+ cells correlated with the
      associated increases in eosinophils (r = 0.78, p = 0.001). Colocalization studies
      revealed that the majority of RANTES mRNA+ cells were macrophages (51%) followed
      by eosinophils (15%), T lymphocytes (11%), and mast cells (3%). Our results
      demonstrate that allergen-induced rhinitis is associated with release of RANTES
      and upregulation of RANTES mRNA and protein+ cells, predominantly macrophages, in
      the nasal mucosa. RANTES synthesis, release, or receptor antagonism may represent
      a potential target for antiallergy treatment.

PMID- 9032216
TI  - Glucocorticoids induce beta2-adrenergic receptor function in human nasal mucosa.
AB  - Glucocorticoids are hypothesized to induce beta2-adrenergic receptors (beta2-R)
      and their functions. The ability of dexamethasone (DEX) in vitro and
      beclomethasone dipropionate (BDP) in vivo to induce beta2-R messenger RNA (mRNA)
      and function was investigated in human nasal mucosa. In this tissue, albuterol
      does not stimulate exocytosis either in vivo or in vitro (Mullol and coworkers,
      1992). Therefore, induction of beta2-R-mediated glandular exocytosis by
      glucocorticoids was proposed as an unambiguous outcome measure. Human nasal
      mucosa was cultured for 3 d with and without 1 microM DEX, then challenged with
      media or 100 microM albuterol. Culture supernatants were collected for
      measurement of exocytosed glandular products. Explant mRNA was extracted for
      reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ
      hybridization of beta2-R mRNA performed. In vivo, normal subjects received saline
      or BDP for 3 d before albuterol nasal provocation. Concentrations of exocytosed
      products were measured in nasal secretions. RNA was extracted from nasal
      epithelial scrapings for RT-PCR. In vitro, DEX treatment induced albuterol
      mediated glandular exocytosis (p < 0.04), and increased the steady-state beta2
      R/beta-actin mRNA ratio (p < 0.05), and expression of beta2-R mRNA in glands. In
      vivo, BDP increased the beta2-R/beta-actin mRNA ratio in epithelial scrapings (p
      < 0.04), but did not induce albuterol-mediated glandular secretion. We conclude
      that glucocorticoids increase steady-state beta2-R mRNA levels in vivo and in
      vitro, and can induce beta2-R function as assessed by submucosal gland exocytosis
      in vitro. While topical BDP induced epithelial beta2-R mRNA, it did not modulate
      exocytosis from the deeper submucosal glands.

PMID- 9032218
TI  - A longitudinal study of transmission of tuberculosis in a large prison
      population.
AB  - The purpose of this study was to determine the extent of transmission of
      tuberculosis in a large prison population over an 18-mo period. Restriction
      fragment-length polymorphism (RFLP) analysis of isolates of Mycobacterium
      tuberculosis was performed, using the insertion sequence IS6110 and the plasmid
      pTBN12. Patients infected with strains having the same fingerprint were grouped
      in clusters. Medical records were reviewed and movement of inmates among prisons
      was examined for selected patients. Tuberculosis was diagnosed in 216 inmates
      (case rate = 2,283 per 100,000 per year). Isolates from 210 (97%) patients were
      fingerprinted, 155 (74%) were grouped in 25 clusters, and 55 (26%) showed a
      unique fingerprint. Recent infection was inferred in 62% of these patients.
      Eighty-four percent (161 of 192) of patients tested were human immunodeficiency
      virus (HIV)-positive, of whom 121 were in clusters and 40 were not (p = 0.74).
      Patients in clusters were less adherent with tuberculosis treatment than those
      not in clusters (p < 0.05), and prison transmission of resistant strains was
      observed. It is crucial that infection control guidelines be fully implemented in
      the prison setting to prevent tuberculosis transmission.

PMID- 9032217
TI  - Effect of nafamostat mesilate on pulmonary vascular injury induced by
      lipopolysaccharide in rats.
AB  - Nafamostat mesilate (NM) is a synthetic protease inhibitor that is capable of
      inhibiting the various coagulation factors such as factor VIIa and thrombin. To
      determine whether NM may also be useful in treating adult respiratory distress
      syndrome (ARDS) related in sepsis, we investigated the effect of NM on
      lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats. The
      intraperitoneal administration of NM prevented the pulmonary vascular injury and
      coagulation abnormalities induced by LPS. DEGR-factor VIIa, a selective inhibitor
      of factor VIIa, prevented the coagulation abnormalities, but not the pulmonary
      vascular injury, induced by LPS. NM did not reduce LPS-induced increase in
      pulmonary accumulation of leukocytes. NM did not inhibit the increase in the
      plasma concentration of tumor necrosis factor-alpha (TNF-alpha) observed after
      administration of LPS. NM did not inhibit the function of activated neutrophils
      in vitro. Plasma values of total serum hemolytic complement (CH50) were markedly
      decreased after the administration of LPS. NM inhibited the LPS-induced decrease
      in plasma CH50 values. Findings suggest that NM may reduce the pulmonary vascular
      injury as well as the coagulation abnormalities induced by LPS. The former effect
      may be independent of the anticoagulant effect but dependent on the inhibitory
      effect of the activation of the complement system in rats administered LPS.

PMID- 9032219
TI  - Autocrine modulation of IL-8 production by sputum neutrophils in chronic
      bronchial sepsis.
AB  - We examined the activity of neutrophils isolated from sputum and blood of
      subjects with chronic bronchial sepsis in terms of interleukin-8 (IL-8), IL
      1beta, and tumor necrosis factor-alpha (TNF alpha) production. In sputum, the
      numbers of neutrophils correlated with the concentrations of these cytokines.
      Sputum neutrophils constitutively secreted large amounts of IL-8, IL-1beta, and
      TNF alpha. The patterns of secretion, however, differed from those of blood
      neutrophils stimulated with bacterial lipopolysaccharide (LPS). Cytokine
      secretion was time-dependent and was inhibited by cycloheximide and
      dexamethasone. IL-10 inhibition of IL-8 production by sputum neutrophils was
      significantly less than that noted with activated neutrophils. Antibody to IL
      1beta but not to TNF alpha, inhibited IL-8 secretion by sputum neutrophils,
      contrasting with results found using blood neutrophils. Incubation of blood
      neutrophils in sputum sol induced a similar cytokine secretion profile to that
      following exposure to LPS. The inhibitory effects on IL-8 protein production
      correlated with messenger RNA (mRNA) gene expression. These observations indicate
      that neutrophils are a significant source of IL-8 in purulent sputum, and that an
      autocrine loop involving IL-1beta maintains secretion within the bronchus lumen.

PMID- 9032220
TI  - A new tongue advancement technique for sleep-disordered breathing: side effects
      and efficacy.
AB  - We examined the efficacy and the acceptance of an oral device (SnorEx) causing a
      forward displacement of the tongue for the treatment of sleep-disordered
      breathing (SDB). Twenty-three consecutive subjects with SDB were investigated.
      Noncompliance (NC) of use of the oral appliance was observed in 74% (17 of 23) of
      the subjects. NC patients were characterized by unacceptable local side effects
      of the prosthesis, lacking improvement of indicators of daytime well-being, and a
      missing reduction of the respiratory disturbance index (RDI). The device was
      tolerated without side effects in 26% (6 of 23) of the subjects. In these
      compliant (C) subjects the RDI, EDS, and snoring improved significantly (p <
      0.05) compared with baseline values. After 6 mo using the device, five of the six
      C patients were still using it. We conclude that the high rate of noncompliance
      and the low efficacy of the SnorEx prosthesis preclude large-scale use of this
      treatment modality in patients with SDB and snoring since the local side effects
      are the principal cause of NC. No useful predictive parameter of treatment
      compliance or treatment success was found. Thus, this dental appliance should be
      prescribed only for selected patients failing other treatment modalities seen by
      an experienced sleep-disorders specialist.

PMID- 9032221
TI  - Progressive obstructive lung disease associated with microscopic polyangiitis.
AB  - Small airway involvement and progressive severe airflow obstruction are
      unexpected features in patients with microscopic polyangiitis. We report the case
      of a patient with microscopic polyangiitis and circulating anti-neutrophil
      cytoplasmic antibodies (ANCA), who developed pulmonary hyperinflation and airflow
      obstruction over a 7-yr period. Systemic manifestations of this vasculitis
      improved under corticosteriods and cyclophosphamid therapy, a treatment that did
      not influence either the very high level of anti-myeloperoxidase antibodies or
      the ventilatory impairment. Small airway involvement was suspected on the basis
      of pathologic small airway lesions and a mild emphysematous pattern on computed
      tomography (CT) scan, which was out of proportion with the severity of the
      obstructive lung disease.

PMID- 9032222
TI  - Combined therapy with inhaled nitric oxide and intravenous prostacyclin in an
      infant with alveolar-capillary dysplasia.
AB  - Severe persistent pulmonary hypertension of the newborn (PPHN) remains a
      significant cause of neonatal morbidity and mortality with limited effective
      treatment options. We present the first case of a neonate with PPHN treated
      concurrently with inhaled nitric oxide (iNO) and intravenous prostacyclin (PGI2).
      He ultimately was diagnosed with alveolar-capillary dysplasia, a rare and fatal
      cause of pulmonary hypertension. However, his partial response to treatment
      demonstrates a possible role for combined therapy with iNO and PGI2 in infants
      with severe PPHN.

PMID- 9032223
TI  - Synergistic effect of nitric oxide and vasoactive intestinal peptide on
      bronchoprotection against histamine in anesthetized guinea pigs.
AB  - Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be
      nonadrenergic, noncholinergic (NANC) inhibitory neurostransmitters in the
      airways. It seems likely that these neurotransmitters may be coreleased and act
      as functional antagonists against bronchoconstrictor stimuli. In the present
      study, we examined the synergistic effect of NO and VIP on bronchoprotection
      against histamine in anesthetized guinea pigs. The NO donor, S-nitroso-N
      acetylpenicillamine (SNAP) significantly inhibited histamine-induced
      bronchoconstriction in a dose-dependent manner. VIP also inhibited histamine
      induced bronchoconstriction in a dose-dependent manner, but this
      bronchoprotective effect was short-lived. Additionally, VIP (10(-9) M) had no
      significant bronchoprotective effect, but a subthreshold dose of SNAP (10(-7) M)
      significantly potentiated VIP (10(-9) M)-induced bronchoprotection against
      histamine. Moreover, SNAP (10(-7) M) significantly enhanced VIP (10(-7) M)
      induced bronchoprotection for a longer period of time. On the other hand, VIP
      (10(-9) M) also significantly potentiated SNAP-induced bronchoprotection against
      histamine. In conclusion, combination therapy with NO donor and VIP receptor
      agonist may have important advantages in the treatment of bronchial asthma, and
      both NO and VIP may contribute in complementary fashion to the NANC-induced
      relaxant response in guinea pig airways.

PMID- 9032224
TI  - Tachykinin-independent effects of capsaicin on smooth muscle in human isolated
      bronchi.
AB  - Contractile and relaxant responses to capsaicin and resiniferatoxin were examined
      in human isolated bronchus (5-12 mm o.d.). Bronchi isolated from 10 of 16 lungs
      contracted in response to capsaicin. The contractions averaged 20% of maximal
      contraction at 1 microM and averaged > 40% maximal contraction at 300 microM (the
      highest concentration studied). The capsaicin-induced contractions were mimicked
      by resiniferatoxin (0.1-10 microM) and inhibited by the putative capsaicin
      receptor antagonist, capsazepine (10 microM). The contractile response to
      capsaicin was not affected by the potent NK-2 selective antagonist SR 48968 (0.3
      microM), whereas responses to concentrations of neurokinin A (10 nM), neurokinin
      B (0.1 microM), substance P (1 microM), neuropeptide gamma (10 nM), and
      neuropeptide K (10 nM) which produced similar-size contractions were almost
      abolished by 0.1 microM SR 48968. The bronchi isolated from 8 of 16 lungs also
      exhibited relaxations in response to capsaicin. Capsaicin-induced relaxations
      were not inhibited by the nitric oxide synthase inhibitor L-nitro-n-arginine (10
      microM). In whole-cell patch-clamp experiments on human cultured airway smooth
      muscle cells, capsaicin was found to enhance outward currents due to the
      activation of charybdotoxin-sensitive large conductance Ca2+-activated K+
      channels. Neither the capsaicin-induced contractions nor the relaxations were
      mimicked by angiotensin II, bombesin, or calcitonin gene-related peptide at
      concentrations up to 1 microM. These results suggest that capsaicin and
      resiniferatoxin can alter smooth muscle tone, but this response does not appear
      to involve substance P or related neurokinins. Relaxations to capsaicin may,
      however, involve the activation of large conductance Ca2+-activated K+ channels.

PMID- 9032226
TI  - Adverse effects of crystalline silica exposure. American Thoracic Society
      Committee of the Scientific Assembly on Environmental and Occupational Health.

PMID- 9032225
TI  - Pathology of the surfactant system of the mature lung.

PMID- 9032227
TI  - Serum indicators of free radical activity in idiopathic pulmonary fibrosis.

PMID- 9032228
TI  - How important is IgE-mediated reaction in childhood asthma?

PMID- 9032229
TI  - Tuberculosis screening for immigrants and refugees: diagnostic outcomes in the
      state of Hawaii.

PMID- 9032230
TI  - A minimal regulatory region maintains constitutive expression of the max gene.
AB  - Max is a basic helix-loop-helix/leucine zipper protein that forms heterodimers
      with the Myc family of proteins to promote cell growth and with the Mad/Mxi1
      family of proteins to inhibit cell growth. The role of Max as the obligate
      binding partner for these two protein families necessitates the observed
      constitutive expression and relatively long half-life of the max mRNA under a
      variety of growth conditions. In this study, we have used the chicken max gene to
      map DNA elements maintaining max gene expression in vertebrate cells. We have
      identified a minimal regulatory region (MRR) that resides within 115 bp of the
      max translation initiation site and that possesses an overall structure typical
      of TATA-less promoters. Within the MRR are two consensus binding sites for Sp1, a
      ubiquitously expressed transcription factor that plays a role in the expression
      of many constitutive genes. Interestingly, we show that direct binding by Sp1 to
      these sites is not required for MRR-mediated transcription. Instead, the
      integrity of a 20-bp DNA element in the MRR is required for transcriptional
      activity, as is the interaction of this DNA element with a 90-kDa cellular
      protein. Our data suggest that it is the persistence of this 90-kDa protein in
      vertebrate cells which drives max gene expression, insulates the max promoter
      from the dramatic changes in transcription that accompany cell growth and
      development, and ensures that adequate levels of Max will be available to
      facilitate the function of the Myc, Mad, and Mxi1 families of proteins.

PMID- 9032231
TI  - E2F-1 cooperates with topoisomerase II inhibition and DNA damage to selectively
      augment p53-independent apoptosis.
AB  - Mutations in the retinoblastoma (pRb) tumor suppressor pathway including its
      cyclin-cdk regulatory kinases, or cdk inhibitors, are a hallmark of most cancers
      and allow unrestrained E2F-1 transcription factor activity, which leads to
      unregulated G1-to-S-phase cell cycle progression. Moderate levels of E2F-1
      overexpression are tolerated in interleukin 3 (IL-3)-dependent 32D.3 myeloid
      progenitor cells, yet this induces apoptosis when these cells are deprived of IL
      3. However, when E2F activity is augmented by coexpression of its heterodimeric
      partner, DP-1, the effects of survival factors are abrogated. To determine
      whether enforced E2F-1 expression selectively sensitizes cells to cytotoxic
      agents, we examined the effects of chemotherapeutic agents and radiation used in
      cancer therapy. E2F-1 overexpression in the myeloid cells preferentially
      sensitized cells to apoptosis when they were treated with the topoisomerase II
      inhibitor etoposide. Although E2F-1 alone induces moderate levels of p53 and
      treatment with drugs markedly increased p53, the deleterious effects of etoposide
      in E2F-1-overexpressing cells were independent of p53 accumulation. Coexpression
      of Bcl-2 and E2F-1 in 32D.3 cells protected them from etoposide-mediated
      apoptosis. However, Bcl-2 also prevented apoptosis of these cells upon exposure
      to 5-fluorouracil and doxorubicin, which were also cytotoxic for control cells.
      Pretreating E2F-1-expressing cells with ICRF-193, a second topoisomerase II
      inhibitor that does not damage DNA, protected the cells from etoposide-induced
      apoptosis. However, ICRF-193 cooperated with DNA-damaging agents to induce
      apoptosis. Therefore, topoisomerase II inhibition and DNA damage can cooperate to
      selectively induce p53-independent apoptosis in cells that have unregulated E2F-1
      activity resulting from mutations in the pRb pathway.

PMID- 9032232
TI  - Effect of association with adenylyl cyclase-associated protein on the interaction
      of yeast adenylyl cyclase with Ras protein.
AB  - Posttranslational modification of Ras protein has been shown to be critical for
      interaction with its effector molecules, including Saccharomyces cerevisiae
      adenylyl cyclase. However, the mechanism of its action was unknown. In this
      study, we used a reconstituted system with purified adenylyl cyclase and Ras
      proteins carrying various degrees of the modification to show that the
      posttranslational modification, especially the farnesylation step, is responsible
      for 5- to 10-fold increase in Ras-dependent activation of adenylyl cyclase
      activity even though it has no significant effect on their binding affinity. The
      stimulatory effect of farnesylation is found to depend on the association of
      adenylyl cyclase with 70-kDa adenylyl cyclase-associated protein (CAP), which was
      known to be required for proper in vivo response of adenylyl cyclase to Ras
      protein, by comparing the levels of Ras-dependent activation of purified adenylyl
      cyclase with and without bound CAP. The region of CAP required for this effect is
      mapped to its N-terminal segment of 168 amino acid residues, which coincides with
      the region required for the in vivo effect. Furthermore, the stimulatory effect
      is successfully reconstituted by in vitro association of CAP with the purified
      adenylyl cyclase molecule lacking the bound CAP. These results indicate that the
      association of adenylyl cyclase with CAP is responsible for the stimulatory
      effect of posttranslational modification of Ras on its activity and that this may
      be the mechanism underlying its requirement for the proper in vivo cyclic AMP
      response.

PMID- 9032233
TI  - Interaction of Ets-1 and the POU-homeodomain protein GHF-1/Pit-1 reconstitutes
      pituitary-specific gene expression.
AB  - The pituitary-specific, POU-homeodomain factor GHF-1/Pit-1 is necessary, but not
      sufficient, for cell-specific expression of prolactin (PRL), growth hormone (GH),
      and thyrotropin. Combinatorial interactions of GHF-1 with other factors are
      likely to be required; however, such factors and their mechanisms of action
      remain to be elucidated. Here we identify Ets-1 as a factor that functionally and
      physically interacts with GHF-1 to fully reconstitute proximal PRL promoter
      activity. In contrast, Ets-2 has no effect, and the alternatively spliced GHF
      2/Pit-1beta variant fails to synergize with Ets-1. The Ets-1-GHF-1 synergy
      requires a composite Ets-1-GHF-1 cis element and is dependent on an Ets-1
      specific protein domain. Furthermore, the ancestrally related and GHF-1-dependent
      GH promoter, which lacks this composite element, does not exhibit this response.
      Finally, Ets-1, but not Ets-2, binds directly to GHF-1 and GHF-2. These data show
      that a functional interaction of GHF-1 and Ets-1, acting via a composite DNA
      element, is required to establish lactotroph-specific PRL gene expression, thus
      providing a molecular mechanism by which GHF-1 can discriminate between the GH
      and PRL genes. These results underscore the importance of transcription factors
      that are distinct from, but interact with, homeobox proteins to establish lineage
      specific gene expression.

PMID- 9032234
TI  - Posttranscriptional regulation of urokinase receptor mRNA: identification of a
      novel urokinase receptor mRNA binding protein in human mesothelioma cells.
AB  - Treatment of human pleural mesothelioma (MS-1) cells with phorbol myristate
      acetate (PMA) and cycloheximide results in 17- and 10-fold, respectively,
      increases in steady-state expression of urokinase-type plasminogen activator
      receptor (uPAR) mRNA. Studies of transcriptional inhibition by actinomycin D
      showed four- and sixfold extensions of uPAR mRNA half-life in MS-1 cells treated
      with PMA and cycloheximide, respectively, suggesting that uPAR gene expression
      involves a posttranscriptional regulatory mechanism. Using gel mobility shift and
      UV cross-linking assays, we identified a 50-kDa uPAR mRNA binding protein (uPAR
      mRNABp) that selectively bound to a 51-nucleotide (nt) fragment of mRNA
      corresponding to the uPAR coding region. We investigated the possibility that
      this 51-nt protein binding fragment of uPAR mRNA contains regulatory information
      for message stability. Chimeric beta-globin/uPAR/beta-globin mRNA containing the
      51-nt protein binding fragment was able to destabilize otherwise stable beta
      globin mRNA. Conversely, a control chimeric beta-globin/uPAR/beta-globin mRNA
      containing a 51-nt fragment of the uPAR coding region that does not bind uPAR
      mRNABp was stable under identical conditions. Binding of uPAR mRNABp to uPAR mRNA
      was abolished after treatment with cycloheximide and rapidly down-regulated by
      PMA. These data suggest that the 51-nt protein binding fragment of uPAR mRNA may
      be involved in mRNA turnover as well as in cycloheximide-induced uPAR message
      stabilization. Our results indicate a novel mechanism of uPAR gene regulation in
      which cis elements within a 51-nt coding region interact with a uPAR mRNABp to
      regulate uPAR message stability.

PMID- 9032235
TI  - The insulin-like growth factor I receptor as a physiologically relevant target of
      p53 in apoptosis caused by interleukin-3 withdrawal.
AB  - The wild-type p53 protein is known to modulate apoptosis induced in 32D murine
      hemopoietic cells by interleukin-3 withdrawal. In 32D cells and in 32D cells
      constitutively expressing a temperature-sensitive mutant of p53 (32Dtsp53),
      overexpression of a wild-type (but not a mutant) insulin-like growth factor I
      receptor (IGF-IR) protects these cells from apoptosis. A tsp53 in its wild-type
      conformation causes a decrease in the levels of IGF-IRs, and this decrease is
      accompanied by increased sensitivity of these cells to apoptosis. However, when
      the expression of the IGF-IR cDNA is regulated by a viral promoter, IGF-IR levels
      are not decreased by a wild-type p53, and apoptosis does not occur. These
      findings show that, in 32Dtsp53 cells, the IGF-IR is a physiologically relevant
      target of p53 in the process of apoptosis.

PMID- 9032236
TI  - Functional identification of a Leishmania gene related to the peroxin 2 gene
      reveals common ancestry of glycosomes and peroxisomes.
AB  - Glycosomes are membrane-bounded microbody organelles that compartmentalize
      glycolysis as well as other important metabolic processes in trypanosomatids. The
      compartmentalization of these enzymatic reactions is hypothesized to play a
      crucial role in parasite physiology. Although the metabolic role of glycosomes
      differs substantially from that of the peroxisomes that are found in other
      eukaryotes, similarities in signals targeting proteins to these organelles
      suggest that glycosomes and peroxisomes may have evolved from a common ancestor.
      To examine this hypothesis, as well as gain insights into the function of the
      glycosome, we used a positive genetic selection procedure to isolate the first
      Leishmania mutant (gim1-1 [glycosome import] mutant) with a defect in the import
      of glycosomal proteins. The mutant retains glycosomes but mislocalizes a subset
      glycosomal proteins to the cytoplasm. Unexpectedly, the gim1-1 mutant lacks lipid
      bodies, suggesting a heretofore unknown role of the glycosome. We used genetic
      approaches to identify a gene, GIM1, that is able to restore import and lipid
      bodies. A nonsense mutation was found in one allele of this gene in the mutant
      line. The predicted Gim1 protein is related the peroxin 2 family of integral
      membrane proteins, which are required for peroxisome biogenesis. The similarities
      in sequence and function provide strong support for the common origin model of
      glycosomes and peroxisomes. The novel phenotype of gim1-1 and distinctive role of
      Leishmania glycosomes suggest that future studies of this system will provide a
      new perspective on microbody biogenesis and function.

PMID- 9032237
TI  - PCF11 encodes a third protein component of yeast cleavage and polyadenylation
      factor I.
AB  - Cleavage and polyadenylation factor I (CF I) is one of four factors required in
      vitro for yeast pre-mRNA 3'-end processing. Two protein components of this
      factor, encoded by genes RNA14 and RNA15, have already been identified. We
      describe here another gene, PCF11 (for protein 1 of CF I), that genetically
      interacts with RNA14 and RNA15 and which presumably codes for a third protein
      component of CF I. This gene was isolated in a two-hybrid screening designed to
      identify proteins interacting with Rna14 and Rna15. PCF11 is an essential gene
      encoding for a protein of 626 amino acids having an apparent molecular mass of 70
      kDa. Thermosensitive mutations in PCF11 are synergistically lethal with
      thermosensitive alleles of RNA14 and RNA15. The Pcf11-2 thermosensitive strain
      shows a shortening of the poly(A) tails and a strong decrease in the steady-state
      level of actin transcripts after a shift to the nonpermissive temperature as do
      the thermosensitive alleles of RNA14 and RNA15. Extracts from the pcf11-1 and
      pcf11-2 thermosensitive strains and the wild-type strain, when Pcf11 is
      neutralized by specific antibodies, are deficient in cleavage and
      polyadenylation. Moreover, fractions obtained by anion-exchange chromatography of
      extracts from the wild-type strain contain both Pcf11 and Rna15 in the same
      fractions, as shown by immunoblotting with a Pcf11-specific antibody.

PMID- 9032238
TI  - A basic helix-loop-helix-leucine zipper transcription complex in yeast functions
      in a signaling pathway from mitochondria to the nucleus.
AB  - The expression of some nuclear genes in Saccharomyces cerevisiae, such as the
      CIT2 gene, which encodes a glyoxylate cycle isoform of citrate synthase, is
      responsive to the functional state of mitochondria. Previous studies identified a
      basic helix-loop-helix-leucine zipper (bHLH/Zip) transcription factor encoded by
      the RTG1 gene that is required for both basal expression of the CIT2 gene and its
      increased expression in respiratory-deficient cells. Here, we describe the
      cloning and characterization of RTG3, a gene encoding a 54-kDa bHLH/Zip protein
      that is also required for CIT2 expression. Rtg3p binds together with Rtg1p to two
      identical sites oriented as inverted repeats 28 bp apart in a regulatory upstream
      activation sequence element (UASr) in the CIT2 promoter. The core binding site
      for the Rtg1p-Rtg3p heterodimer is 5'-GGTCAC-3', which differs from the canonical
      E-box site, CANNTG, to which most other bHLH proteins bind. We demonstrate that
      both of the Rtg1p-Rtg3p binding sites in the UAS(r) element are required in vivo
      and act synergistically for CIT2 expression. The basic region of Rtg3p conforms
      well to the basic region of most bHLH proteins, whereas the basic region of Rtg1p
      does not. These findings suggest that the Rtg1p-Rtg3p complex interacts in a
      novel way with its DNA target sites.

PMID- 9032241
TI  - The decline in human Alu retroposition was accompanied by an asymmetric decrease
      in SRP9/14 binding to dimeric Alu RNA and increased expression of small
      cytoplasmic Alu RNA.
AB  - Alu interspersed elements are inserted into the genome by a retroposition process
      that occurs via dimeric Alu RNA and causes genetic disorders in humans. Alu RNA
      is labile and can be diverted to a stable left monomer transcript known as small
      cytoplasmic Alu (scAlu) RNA by RNA 3' processing, although the relationship
      between Alu RNA stability, scAlu RNA production, and retroposition has been
      unknown. In vivo, Alu and scAlu transcripts interact with the Alu RNA-binding
      subunit of signal recognition particle (SRP) known as SRP9/14. We examined RNAs
      corresponding to Alu sequences that were differentially active during primate
      evolution, as well as an Alu RNA sequence that is currently active in humans.
      Mutations that accompanied Alu RNA evolution led to changes in a conserved
      structural motif also found in SRP RNAs that are associated with thermodynamic
      destabilization and decreased affinity of the Alu right monomer for SRP9/14. In
      contrast to the right monomer, the Alu left monomer maintained structural
      integrity and high affinity for SRP9/14, indicating that scAlu RNA has been under
      selection during human evolution. Loss of Alu right monomer affinity for SRP9/14
      is associated with scAlu RNA production from Alu elements in vivo. Moreover, the
      loss in affinity coincided with decreased rates of Alu amplification during
      primate evolution. This indicates that stability of the Alu right monomer is a
      critical determinant of Alu retroposition. These results provide insight into Alu
      mobility and evolution and into how retroposons may interact with host proteins
      during genome evolution.

PMID- 9032240
TI  - Expression of constitutively active alpha-PAK reveals effects of the kinase on
      actin and focal complexes.
AB  - The family of p21-activated protein kinases (PAKs) appear to be present in all
      organisms that have Cdc42-like GTPases. In mammalian cells, PAKs have been
      implicated in the activation of mitogen-activated protein kinase cascades, but
      there are no reported effects of these kinases on the cytoskeleton. Recently we
      have shown that a Drosophila PAK is enriched in the leading edge of embryonic
      epithelial cells undergoing dorsal closure (N. Harden, J. Lee, H.-Y. Loh, Y.-M.
      Ong, I. Tan, T. Leung, E. Manser, and L. Lim, Mol. Cell. Biol. 16:1896-1908,
      1996), where it colocalizes with structures resembling focal complexes. We show
      here by transfection that in epithelial HeLa cells alpha-PAK is recruited from
      the cytoplasm to distinct focal complexes by both Cdc42(G12V) and Rac1(G12V),
      which themselves colocalize to these sites. By deletion analysis, the N terminus
      of PAK is shown to contain targeting sequences for focal adhesions which indicate
      that these complexes are the site of kinase function in vivo. Cdc42 and Rac1
      cause alpha-PAK autophosphorylation and kinase activation. Mapping alpha-PAK
      autophosphorylation sites has allowed generation of a constitutively active
      kinase mutant. By fusing regions of Cdc42 to the C terminus of PAK, activated
      chimeras were also obtained. Plasmids encoding these different constitutively
      active alpha-PAKs caused loss of stress fibers when introduced into both HeLa
      cells and fibroblasts, which was similar to the effect of introducing Cdc42(G12V)
      or Rac1(G12V). Significantly dramatic losses of focal adhesions were also
      observed. These combined effects resulted in retraction of the cell periphery
      after plasmid microinjection. These data support our previous suggestions of a
      role for PAK downstream of both Cdc42 and Rac1 and indicate that PAK functions
      include the dissolution of stress fibers and reorganization of focal complexes.

PMID- 9032239
TI  - Lipopolysaccharide and Raf-1 kinase regulate secretory interleukin-1 receptor
      antagonist gene expression by mutually antagonistic mechanisms.
AB  - Lipopolysaccharide (LPS) treatment of monocytic cells has been shown to activate
      the Raf-1/mitogen-activated protein kinase (MAPK) signaling pathway and to
      increase secretory interleukin-1 receptor antagonist (sIL-1Ra) gene expression.
      The significance of the activation of the Raf-1/MAPK signaling pathway to LPS
      regulation of sIL-1Ra gene expression, however, has not been determined. This
      study addresses the role of the Raf-1/MAPK signaling pathway in regulation of sIL
      1Ra gene expression by LPS. Cotransfection of the murine macrophage cell line RAW
      264.7 with a 294-bp sIL-1Ra promoter/luciferase construct (pRA-294-luc) and a
      constitutively active Raf-1 kinase expression vector (pRSV-Raf-BXB) resulted in
      induction of sIL-1Ra promoter activity, indicating that Raf-1, like LPS, can
      regulate sIL-1Ra promoter activity. An in vitro MAPK analysis indicated that both
      LPS treatment and pRSV-Raf-BXB transfection of RAW 264.7 cells increases p42 MAPK
      activity. An in vitro Raf-1 kinase assay, however, failed to detect LPS-induced
      Raf-1 kinase activity in RAW 264.7 cells, suggesting that in RAW 264.7 cells, Raf
      1 kinase is not an activating component of the LPS signaling pathway regulating
      MAPK activity or sIL-1Ra promoter activity. This observation was supported by
      results from transfection studies which demonstrated that expression of a
      dominant-inhibitory Raf-1 mutant in RAW 264.7 cells does not inhibit LPS-induced
      MAPK activity or sIL-1Ra promoter activity, indicating that LPS-induced sIL-1Ra
      promoter activation occurs independent of the Raf-1/MAPK signaling pathway. In
      additional studies, cotransfection of RAW 264.7 cells with pRA-294-luc and
      increasing amounts of pRSV-Raf-BXB caused a dose-dependent inhibition of LPS
      induced sIL-1Ra promoter activity, indicating that the role of the Raf-1 pathway
      in the regulation of sIL-1Ra promoter activity by LPS is as an antagonizer.
      Interestingly, LPS treatment of RAW 264.7 cells, cotransfected with pRA-294-luc
      and pRSV-Raf-BXB, also inhibited pRSV-Raf-BXB-induced sIL-1Ra promoter activity,
      suggesting that inductions of sIL-1Ra promoter activity by LPS and Raf-1 actually
      occur by mutually antagonistic mechanisms. In support of this conclusion, sIL-1Ra
      promoter mapping studies indicated that LPS and Raf-1 responses localized to
      different regions of the sIL-1Ra promoter. Further studies demonstrated that
      mutual antagonism between the LPS and Raf-1 kinase pathways is not promoter
      specific, as the same phenomenon is observed in assays using a c-fos
      enhancer/thymidine kinase promoter/luciferase construct (pc-fos-TK81-luc).
      Additionally, mutual antagonism with regard to sIL-1Ra promoter activity also was
      observed between the LPS and MEK kinase pathways, indicating that mutual
      antagonism can occur in more than one MAPK activation pathway.

PMID- 9032242
TI  - Regulation of gene expression during meiosis in Saccharomyces cerevisiae: SPR3 is
      controlled by both ABFI and a new sporulation control element.
AB  - The SPR3 gene encodes a sporulation-specific homolog of the yeast Cdc3/10/11/12
      family of bud neck filament proteins. It is expressed specifically during meiosis
      and sporulation in Saccharomyces cerevisiae. Analysis of the sporulation-specific
      regulation of SPR3 has shown that it is strongly activated under sporulating
      conditions but shows low levels of expression under nonsporulating conditions. A
      palindromic sequence located near the TATA box is essential to the developmental
      regulation of this gene and is the only element directly activating SPR3 at the
      right time during sporulation. Within the palindrome is a 9-bp sequence,
      gNCRCAAA(A/T) (midsporulation element [MSE]), found in the known control regions
      of three other sporulation genes. A previously identified ABFI element is also
      needed for activation. The MSE has been shown to activate a heterologous promoter
      (CYC1) in a sporulation-specific manner. Related sequences, including an
      association of MSE and ABFI elements, have been found upstream of other genes
      activated during the middle stage of S. cerevisiae sporulation. One group of
      these may be involved in spore coat formation or maturation.

PMID- 9032243
TI  - Cdc73p and Paf1p are found in a novel RNA polymerase II-containing complex
      distinct from the Srbp-containing holoenzyme.
AB  - The products of the yeast CDC73 and PAF1 genes were originally identified as RNA
      polymerase II-associated proteins. Paf1p is a nuclear protein important for cell
      growth and transcriptional regulation of a subset of yeast genes. In this study
      we demonstrate that the product of CDC73 is a nuclear protein that interacts
      directly with purified RNA polymerase II in vitro. Deletion of CDC73 confers a
      temperature-sensitive phenotype. Combination of the cdc73 mutation with the more
      severe paf1 mutation does not result in an enhanced phenotype, indicating that
      the two proteins may function in the same cellular processes. To determine the
      relationship between Cdc73p and Paf1p and the recently described holoenzyme form
      of RNA polymerase II, we created yeast strains containing glutathione S
      transferase (GST)-tagged forms of CDC73, PAF1, and TFG2 functionally replacing
      the chromosomal copies of the genes. Isolation of GST-tagged Cdc73p and Paf1p
      complexes has revealed a unique form of RNA polymerase II that contains both
      Cdc73p and Paf1p but lacks the Srbps found in the holoenzyme. The Cdc73p-Paf1p
      RNA polymerase II-containing complex also includes Gal11p, and the general
      initiation factors TFIIB and TFIIF, but lacks TBP, TFIIH, and transcription
      elongation factor TFIIS as well as the Srbps. The Srbp-containing holoenzyme does
      not include either Paf1p or Cdc73p, demonstrating that these two forms of RNA
      polymerase II are distinct. In confirmation of the hypothesis that the two forms
      coexist in yeast cells, we found that a TFIIF-containing complex isolated via the
      GST-tagged Tfg2p construct contains both (i) the Srbps and (ii) Cdc73p and Paf1p.
      The Srbps and Cdc73p-Paf1p therefore appear to define two complexes with
      partially redundant, essential functions in the yeast cell. Using the technique
      of differential display, we have identified several genes whose transcripts
      require Cdc73p and/or Paf1p for normal levels of expression. Our analysis
      suggests that there are multiple RNA polymerase II-containing complexes involved
      in the expression of different classes of protein-coding genes.

PMID- 9032244
TI  - Tyrosine 763 of the murine granulocyte colony-stimulating factor receptor
      mediates Ras-dependent activation of the JNK/SAPK mitogen-activated protein
      kinase pathway.
AB  - The receptor for granulocyte colony-stimulating factor (G-CSF) can mediate
      differentiation and proliferation of hemopoietic cells. A proliferative signal is
      associated with activation of the ERK mitogen-activated protein kinase (MAPK)
      pathway. To determine whether other MAPK pathways are activated by G-CSF
      signalling, we have investigated activation of JNK/SAPK in cells proliferating in
      response to G-CSF. Here we show that G-CSF and interleukin-3 activate JNK/SAPK in
      two hemopoietic cell lines. The region of the G-CSF receptor required for G-CSF
      induced JNK/SAPK activation is located within the C-terminal 68 amino acids of
      the cytoplasmic domain, which contains Tyr 763. Mutation of Tyr 763 to Phe
      completely blocks JNK/SAPK activation. However, the C-terminal 68 amino acids are
      not required for ERK2 activation. We show that activation of JNK/SAPK, like that
      of ERK2, is dependent on Ras but that higher levels of Ras-GTP are associated
      with activation of JNK/SAPK than with activation of ERK2. Two separate functional
      regions of the G-CSF receptor contribute to activation of Ras. The Y763F mutation
      reduces G-CSF-induced Ras activation from 30 to 35% Ras-GTP to 10 to 13% Ras-GTP.
      Low levels of Ras activation (10 to 13% Ras-GTP), which are sufficient for ERK2
      activation, require only the 100 membrane-proximal amino acids. High levels of
      Ras-GTP provided by expression of oncogenic Ras are not sufficient to activate
      JNK/SAPK. An additional signal, also mediated by Tyr 763, is required for
      activation of JNK/SAPK.

PMID- 9032245
TI  - Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor
      signaling and trafficking.
AB  - Shc and insulin receptor substrate 1 (IRS-1) are cytoplasmic substrates of
      tyrosine kinase receptors that engage, localize, and activate downstream SH2
      enzymes. Each contains a phosphotyrosine-binding (PTB) domain that is
      structurally unrelated to SH2 domains. We have designed high-affinity, cellular
      inhibitors of the Shc PTB domain by incorporating nonnatural, phosphatase
      resistant amino acids into short peptides. None of the inhibitors bind the IRS-1
      PTB domain, consistent with distinct specificities for domains. The best
      inhibitor of the Shc domain was introduced by electroporation into Rat1
      fibroblasts that express human insulin receptors. Insulin-stimulated
      phosphorylation of Shc was inhibited, with no effect on IRS-1, and downstream
      effects on mitogen-activated protein kinase and DNA synthesis were both
      inhibited. The PTB domain inhibitor had less influence on epidermal growth factor
      induced effects and essentially no impact on serum- or phorbol ester-induced
      effects. The inhibitor did not affect insulin internalization and its
      degradation. We conclude that the PTB domain of Shc is critical for its
      phosphorylation by the insulin receptor, that Shc is an important mediator of
      insulin's mitogenic effects, and that Shc is not central to insulin receptor
      cycling in these cells. PTB domains can be inhibited selectively in cells and
      represent potential targets for drug discovery.

PMID- 9032246
TI  - The five cleavage-stage (CS) histones of the sea urchin are encoded by a
      maternally expressed family of replacement histone genes: functional equivalence
      of the CS H1 and frog H1M (B4) proteins.
AB  - The cleavage-stage (CS) histones of the sea urchin are known to be maternally
      expressed in the egg, have been implicated in chromatin remodeling of the male
      pronucleus following fertilization, and are the only histone variants present in
      embryonic chromatin up to the four-cell stage. With the help of partial peptide
      sequence information, we have isolated and identified CS H1, H2A, H2B, H3, and H4
      cDNAs from egg poly(A)+ mRNA of the sea urchin Psammechinus miliaris. All five CS
      proteins correspond to replacement histone variants which are encoded by
      replication-independent genes containing introns, poly(A) addition signals, and
      long nontranslated sequences. Transcripts of the CS histone genes could be
      detected only during oogenesis and in development up to the early blastula stage.
      The CS proteins, with the exception of H4, are unique histones which are
      distantly related in sequence to the early, late, and sperm histone subtypes of
      the sea urchin. In contrast, the CS H1 protein displays highest sequence homology
      with the H1M (B4) histone of Xenopus laevis. Both H1 proteins are replacement
      histone variants with very similar developmental expression profiles in their
      respective species, thus indicating that the frog H1M (B4) gene is a vertebrate
      homolog of the CS H1 gene. These data furthermore suggest that the CS histones
      are of ancient evolutionary origin and may perform similar conserved functions
      during oogenesis and early development in different species.

PMID- 9032247
TI  - Rho family GTPases and neuronal growth cone remodelling: relationship between
      increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse
      induced by RhoA and lysophosphatidic acid.
AB  - Rho family GTPases have been assigned important roles in the formation of actin
      based morphologies in nonneuronal cells. Here we show that microinjection of
      Cdc42Hs and Rac1 promoted formation of filopodia and lamellipodia in N1E-115
      neuroblastoma growth cones and along neurites. These actin-containing structures
      were also induced by injection of Clostridium botulinum C3 exoenzyme, which
      abolishes RhoA-mediated functions such as neurite retraction. The C3 response was
      inhibited by coinjection with the dominant negative mutant Cdc42Hs(T17N), while
      the Cdc42Hs response could be competed by coinjection with RhoA. We also
      demonstrate that the neurotransmitter acetylcholine (ACh) can induce filopodia
      and lamellipodia on neuroblastoma growth cones via muscarinic ACh receptor
      activation, but only when applied in a concentration gradient. ACh-induced
      formation of filopodia and lamellipodia was inhibited by preinjection with the
      dominant negative mutants Cdc42Hs(T17N) and Rac1(T17N), respectively.
      Lysophosphatidic acid (LPA)-induced neurite retraction, which is mediated by
      RhoA, was inhibited by ACh, while C3 exoenzyme-mediated neurite outgrowth was
      inhibited by injection with Cdc42Hs(T17N) or Rac1(T17N). Together these results
      suggest that there is competition between the ACh- and LPA-induced morphological
      pathways mediated by Cdc42Hs and/or Rac1 and by RhoA, leading to either neurite
      development or collapse.

PMID- 9032248
TI  - A family of cyclin-like proteins that interact with the Pho85 cyclin-dependent
      kinase.
AB  - In budding yeast, entry into the mitotic cell cycle, or Start, requires the Cdc28
      cyclin-dependent kinase (Cdk) and one of its three associated G1 cyclins, Cln1,
      Cln2, or Cln3. In addition, two other G1 cyclins, Pcl1 and Pcl2, associate with a
      second Cdk, Pho85, to contribute to Start. Although Pho85 is not essential for
      viability, Pcl1,2-Pho85 kinase complexes become essential for Start in the
      absence of Cln1,2-Cdc28 kinases. In addition, Pho85 interacts with a third
      cyclin, Pho80, to regulate acid phosphatase gene expression. Other cellular roles
      for Pho85 cyclin-Cdk complexes are suggested by the multiple phenotypes
      associated with deletion of PHO85, in addition to Start defects and deregulated
      acid phosphatase gene expression. Strains with pho80, pcl1, and pcl2 deletions
      show only a subset of the pho85 mutant phenotypes, suggesting the existence of
      additional Pho85 cyclins (Pcls). We used two-hybrid screening and database
      searching to identify seven additional cyclin-related genes that may interact
      with Pho85. We found that all of the new genes encode proteins that interacted
      with Pho85 in an affinity chromatography assay. One of these genes, CLG1, was
      previously suggested to encode a cyclin, based on the protein's sequence homology
      to Pcl1 and Pcl2. We have named the other genes PCL5, PCL6, PCL7, PCL8, PCL9, and
      PCL10. On the basis of sequence similarities, the PCLs can be divided into two
      subfamilies: the Pcl1,2-like subfamily and the Pho80-like subfamily. We found
      that deletion of members of the Pcl1,2 class of genes resulted in pronounced
      morphological abnormalities. In addition, we found that expression of one member
      of the Pcl1,2 subfamily, PCL9, is cell cycle regulated and is decreased in cells
      arrested in G1 by pheromone treatment. Our studies suggest that Pho85 associates
      with multiple cyclins and that subsets of cyclins may direct Pho85 to perform
      distinct roles in cell growth and division.

PMID- 9032249
TI  - Induction of senescence-like phenotypes by forced expression of hic-5, which
      encodes a novel LIM motif protein, in immortalized human fibroblasts.
AB  - The hic-5 gene encodes a novel protein with Zn finger-like (LIM) motifs, the
      expression of which increases during cellular senescence. The ectopic expression
      of hic-5 in nontumorigenic immortalized human fibroblasts, whose expression
      levels of hic-5 were significantly reduced in comparison with those of mortal
      cells, decreased colony-forming efficiency. Stable clones expressing high levels
      of hic-5 mRNA showed higher levels of mRNAs for several extracellular matrix
      related proteins, along with the alteration of an alternative splicing as seen in
      senescent cells and decreased c-fos inducibility. Furthermore, these clones
      acquired a senescence-like phenotype, such as growth retardation; senescence-like
      morphology; and increased expression of Cip1/WAF1/sdi1 after 20 to 40 population
      doublings. On the other hand, antisense RNA expression of hic-5 in human normal
      diploid fibroblasts delayed the senescence process. HIC-5 was localized in nuclei
      and had affinity for DNA. Based on these observations, we speculated that HIC-5
      affected the expression of senescence-related genes through interacting with DNA
      and thereby induced the senescence-like phenotypes. To our knowledge, hic-5 is
      the first single gene that could induce senescence-like phenotypes in a certain
      type of immortalized human cell and mediate the normal process of senescence.

PMID- 9032251
TI  - Interplay of the E box, the cyclic AMP response element, and HTF4/HEB in
      transcriptional regulation of the neurospecific, neurotrophin-inducible vgf gene.
AB  - vgf is a neurotrophin response-specific, developmentally regulated gene that
      codes for a neurosecretory polypeptide. Its transcription in neuronal cells is
      selectively activated by the neurotrophins nerve growth factor (NGF), brain
      derived neurotrophic factor, and neurotrophin 3, which induce survival and
      differentiation, and not by epidermal growth factor. We studied a short region of
      the rat vgf promoter which is essential for its regulated expression. A cyclic
      AMP response element (CRE) within this region is necessary for NGF induction of
      vgf transcription. Two sites upstream of CRE, an E box and a CCAAT sequence, bind
      nuclear protein complexes and are involved in transcriptional control. The E box
      has a dual role. It acts as an inhibitor in NIH 3T3 fibroblasts, together with a
      second E box located downstream, and as a stimulator in the NGF-responsive cell
      line PC12. By expression screening, we have isolated the cDNA for a basic helix
      loop-helix transcription factor, a homolog of the HTF4/HEB E protein, that
      specifically binds the vgf promoter E box. The E protein was present in various
      cell lines, including PC12 cells, and was a component of a multiprotein nuclear
      complex that binds the promoter in vitro. The E box and CRE cooperate in binding
      to this complex, which may be an important determinant for neural cell-specific
      expression.

PMID- 9032252
TI  - The structure of heterochromatic DNA is altered in polyploid cells of Drosophila
      melanogaster.
AB  - DNA sequences within heterochromatin are often selectively underrepresented
      during development of polyploid chromosomes, and DNA molecules of altered
      structure are predicted to form as a consequence of the underrepresentation
      process. We have identified heterochromatic DNAs of altered structure within
      sequences that are underrepresented in polyploid cells of Drosophila
      melanogaster. Specifically, restriction fragments that extend into centric
      heterochromatin of the minichromosome Dp(1;f)1187 are shortened in polyploid
      cells of both the ovary and salivary gland but not in the predominantly diploid
      cells of the embryo or larval imaginal discs and brains. Shortened DNA molecules
      were also identified within heterochromatic sequences of chromosome III. These
      results suggest that the structure of heterochromatic DNA is altered as a general
      consequence of polyploid chromosome formation and that the shortened molecules
      identified form as a consequence of heterochromatic underrepresentation. Finally,
      alteration of heterochromatic DNA structure on Dp(1;f)1187 was not correlated
      with changes in the variegated expression of the yellow gene located on the
      minichromosome.

PMID- 9032250
TI  - Physical and functional interaction between the human T-cell lymphotropic virus
      type 1 Tax1 protein and the CCAAT binding protein NF-Y.
AB  - Tax1, a potent activator of human T-cell lymphotropic virus type 1 (HTLV-1)
      transcription, has been shown to modulate expression of many cellular genes. Tax1
      does not bind DNA directly but regulates transcription through protein-protein
      interactions with sequence-specific transcription factors. Using the yeast two
      hybrid system to screen for proteins which interact with Tax1, we isolated the B
      subunit of the CCAAT binding protein NF-Y from a HeLa cDNA library. The
      interaction of Tax1 with NF-YB was specific in that NF-YB did not interact with a
      variety of other transcription factors, including human immunodeficiency virus
      Tat, human papillomavirus E6, and Bicoid, or with the M7 (amino acids 29CP-AS)
      Tax1 mutant. However, NF-YB did interact with the C-terminal Tax1 mutants M22
      (130TL-AS) and M47 (319LL-RS). We also show that in vitro-translated NF-YB
      specifically bound to a glutathione S-transferase-Tax1 fusion protein. Further,
      Tax1 coimmunoprecipitated with NF-Y from nuclear extracts of HTLV-1-transformed
      cells, providing evidence for in vivo interaction of Tax1 and NF-YB. We further
      demonstrate that Tax1 specifically activated the NF-Y-responsive DQbeta promoter,
      as well as a minimal promoter which contains only the Y-box element. In addition,
      mutation of the Y-box element alone abrogated Tax1-mediated activation. Taken
      together, these data indicate that Tax1 interacts with NF-Y through the B subunit
      and that this interaction results in activation of the major histocompatibility
      complex class II promoter. Through activation of this and other NF-Y driven
      promoters, the Tax1-NF-Y interaction may play a critical role in causing cellular
      transformation and HTLV-1 pathogenesis.

PMID- 9032254
TI  - A transcriptional enhancer required for the differential expression of the human
      estrogen receptor in breast cancers.
AB  - Breast cancers lacking estrogen receptor (ER) expression have an adverse
      prognosis and fail to respond to endocrine therapy. We have identified a
      transcriptional enhancer in the human ER gene which is differentially active in
      ER-positive (ER+) and ER-negative (ER-) human breast cancer cell lines. Enhancer
      function was mapped to a 35-bp element located from -3778 to -3744 upstream of
      the major human ER mRNA start site, which we have termed ER-EH0 (for estrogen
      receptor enhancer). Gel retardation assays with ER+ and ER- cell lines identified
      multiple DNA-protein complexes which specifically form on this enhancer. One of
      these complexes could be supershifted by anti-Jun or anti-Fos antibodies,
      identifying it as an AP-1-containing complex. Methylation interference assays
      suggest binding of factors to both the AP-1 site and adjacent base pairs.
      Enhancer activity requires both the AP-1 site and these adjacent sequences.
      Mutations introduced into ER-EH0 and the recently described proximal promoter
      element ERF-1 in the context of the full-length promoter confirm ER-EH0 as the
      dominant cis-acting element involved in differential ER expression.

PMID- 9032253
TI  - Molecular and biochemical characterization of xrs mutants defective in Ku80.
AB  - The gene product defective in radiosensitive CHO mutants belonging to ionizing
      radiation complementation group 5, which includes the extensively studied xrs
      mutants, has recently been identified as Ku80, a subunit of the Ku protein and a
      component of DNA-dependent protein kinase (DNA-PK). Several group 5 mutants,
      including xrs-5 and -6, lack double-stranded DNA end-binding and DNA-PK
      activities. In this study, we examined additional xrs mutants at the molecular
      and biochemical levels. All mutants examined have low or undetectable levels of
      Ku70 and Ku80 protein, end-binding, and DNA-PK activities. Only one mutant, xrs
      6, has Ku80 transcript levels detectable by Northern hybridization, but Ku80 mRNA
      was detectable by reverse transcription-PCR in most other mutants. Two mutants,
      xrs-4 and -6, have altered Ku80 transcripts resulting from mutational changes in
      the genomic Ku80 sequence affecting RNA splicing, indicating that the defects in
      these mutants lie in the Ku80 gene rather than a gene controlling its expression.
      Neither of these two mutants has detectable wild-type Ku80 transcript. Since the
      mutation in both xrs-4 and xrs-6 cells results in severely truncated Ku80
      protein, both are likely candidates to be null mutants. Azacytidine-induced
      revertants of xrs-4 and -6 carried both wild-type and mutant transcripts. The
      results with these revertants strongly support our model proposed earlier, that
      CHO-K1 cells carry a copy of the Ku80 gene (XRCC5) silenced by hypermethylation.
      Site-directed mutagenesis studies indicate that previously proposed ATP-binding
      and phosphorylation sites are not required for Ku80 activity, whereas N-terminal
      deletions of more than the first seven amino acids result in severe loss of
      activities.

PMID- 9032255
TI  - Negative protein 1, which is required for function of the chicken lysozyme gene
      silencer in conjunction with hormone receptors, is identical to the multivalent
      zinc finger repressor CTCF.
AB  - The transcriptional repressor negative protein 1 (NeP1) binds specifically to the
      F1 element of the chicken lysozyme gene silencer and mediates synergistic
      repression by v-ERBA, thyroid hormone receptor, or retinoic acid receptor.
      Another protein, CCCTC-binding factor (CTCF), specifically binds to 50-bp-long
      sequences that contain repetitive CCCTC elements in the vicinity of vertebrate c
      myc genes. Previously cloned chicken, mouse, and human CTCF cDNAs encode a highly
      conserved 11-Zn-finger protein. Here, NeP1 was purified and DNA bases critical
      for NeP1-F1 interaction were determined. NeP1 is found to bind a 50-bp stretch of
      nucleotides without any obvious sequence similarity to known CTCF binding
      sequences. Despite this remarkable difference, these two proteins are identical.
      They have the same molecular weight, and NeP1 contains peptide sequences which
      are identical to sequences in CTCF. Moreover, NeP1 and CTCF specifically
      recognize each other's binding DNA sequence and induce identical conformational
      alterations in the F1 DNA. Therefore, we propose to replace the name NeP1 with
      CTCF. To analyze the puzzling sequence divergence in CTCF binding sites, we
      studied the DNA binding of 12 CTCF deletions with serially truncated Zn fingers.
      While fingers 4 to 11 are indispensable for CTCF binding to the human c-myc P2
      promoter site A, a completely different combination of fingers, namely, 1 to 8 or
      5 to 11, was sufficient to bind the lysozyme silencer site F1. Thus, CTCF is a
      true multivalent factor with multiple repressive functions and multiple sequence
      specificities.

PMID- 9032256
TI  - Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein kinase
      by the PTP2 and PTP3 protein tyrosine phosphatases.
AB  - In response to increases in extracellular osmolarity, Saccharomyces cerevisiae
      activates the HOG1 mitogen-activated protein kinase (MAPK) cascade, which is
      composed of a pair of redundant MAPK kinase kinases, namely, Ssk2p and Ssk22p,
      the MAPK kinase Pbs2p, and the MAPK Hog1p. Hog1p is activated by Pbs2p through
      phosphorylation of specific threonine and tyrosine residues. Activated Hog1p is
      essential for survival of yeast cells at high osmolarity. However, expression of
      constitutively active mutant kinases, such as those encoded by SSK2deltaN and
      PBS2(DD), is toxic and results in a lethal level of Hog1p activation.
      Overexpression of the protein tyrosine phosphatase Ptp2p suppresses the lethality
      of these mutations by dephosphorylating Hog1p. A catalytically inactive Cys-to
      Ser Ptp2p mutant (Ptp2(C/S)p) is tightly bound to tyrosine-phosphorylated Hog1p
      in vivo. Disruption of PTP2 leads to elevated levels of tyrosine-phosphorylated
      Hog1p following exposure of cells to high osmolarity. Disruption of both PTP2 and
      another protein tyrosine phosphatase gene, PTP3, results in constitutive Hog1p
      tyrosine phosphorylation even in the absence of increased osmolarity. Thus, Ptp2p
      and Ptp3p are the major phosphatases responsible for the tyrosine
      dephosphorylation of Hog1p. When catalytically inactive Hog1(K/N)p is expressed
      in hog1delta cells, it is constitutively tyrosine phosphorylated. In contrast,
      Hog1(K/N)p, expressed together with wild-type Hog1p, is tyrosine phosphorylated
      only when cells are exposed to high osmolarity. Thus, the kinase activity of
      Hog1p is required for its own tyrosine dephosphorylation. Northern blot analyses
      suggest that Hog1p regulates Ptp2p and/or Ptp3p activity at the
      posttranscriptional level.

PMID- 9032257
TI  - Homologous segments in three subunits of the guanine nucleotide exchange factor
      eIF2B mediate translational regulation by phosphorylation of eIF2.
AB  - eIF2B is a five-subunit guanine nucleotide exchange factor that is negatively
      regulated by phosphorylation of the alpha subunit of its substrate, eIF2, leading
      to inhibition of translation initiation. To analyze this regulatory mechanism, we
      have characterized 29 novel mutations in the homologous eIF2B subunits encoded by
      GCD2, GCD7, and GCN3 that reduce or abolish inhibition of eIF2B activity by eIF2
      phosphorylated on its alpha subunit [eIF2(alphaP)]. Most, if not all, of the
      mutations decrease sensitivity to eIF2(alphaP) without excluding GCN3, the
      nonessential subunit, from eIF2B; thus, all three proteins are critical for
      regulation of eIF2B by eIF2(alphaP). The mutations are clustered at both ends of
      the homologous region of each subunit, within two segments each of approximately
      70 amino acids in length. Several mutations alter residues at equivalent
      positions in two or all three subunits. These results imply that structurally
      similar segments in GCD2, GCD7, and GCN3 perform related functions in eIF2B
      regulation. We propose that these segments form a single domain in eIF2B that
      makes multiple contacts with the alpha subunit of eIF2, around the
      phosphorylation site, allowing eIF2B to detect and respond to phosphoserine at
      residue 51. Most of the eIF2 is phosphorylated in certain mutants, suggesting
      that these substitutions allow eIF2B to accept phosphorylated eIF2 as a substrate
      for nucleotide exchange.

PMID- 9032258
TI  - Costimulation by B7-1 and LFA-3 targets distinct nuclear factors that bind to the
      interleukin-2 promoter: B7-1 negatively regulates LFA-3-induced NF-AT DNA
      binding.
AB  - We have characterized the regulation of nuclear factors involved in
      transcriptional control of the interleukin-2 (IL-2) promoter-enhancer activity in
      Jurkat T cells stimulated with superantigen presented on HLA-DR transfectants
      combined with the ligands LFA-3 (CD58) and B7-1 (CD80). Gel shift analyses showed
      that NF-AT was strongly induced in LFA-3-costimulated Jurkat T cells, suggesting
      that NF-AT is a key target nuclear factor for the CD2-LFA-3 pathway. Studies
      using HLA-DR-B7-1-LFA-3 triple transfectants showed that the LFA-3-induced NF-AT
      DNA binding activity was negatively regulated by B7-1 costimulation. In contrast,
      induction of a CD28 response complex containing only c-Rel proteins was seen
      after B7-1 costimulation. Both LFA-3 costimulation and B7-1 costimulation induced
      the AP-1 and NF-kappaB nuclear factors. Distinct compositions of the NF-AT
      complexes were seen in B7-1- and LFA-3-costimulated cells. LFA-3 induced
      primarily Jun-D, Fra-1, and Fra-2, while B7-1 induced June-D-Fos complexes. In
      contrast, AP-1 and NF-kappaB complexes induced in B7-1- and LFA-3-costimulated T
      cells showed similar contents. Transient transfection of Jurkat T cells with a
      construct encoding the IL-2 enhancer-promoter region (position -500 to +60)
      linked to a luciferase reporter gene revealed that B7-1 costimulation was
      required to induce strong transcriptional activity. Combined B7-1-LFA-3
      costimulation resulted in a synergistic increase in IL-2 transcriptional
      activity. Multimers of the AP-1, NF-AT, NF-kappaB, and CD28 response elements
      showed distinct kinetics and activity after LFA-3 and B7-1 costimulation and
      revealed that B7-1 and LFA-3 converge to superinduce transcriptional activity of
      the AP-1, NF-AT, and CD28 response elements. Transcriptional studies with an IL-2
      enhancer-promoter carrying a mutation in the CD28 response element site revealed
      that the activity was reduced by 80% after B7-1 and B7-1-LFA-3 costimulation
      whereas the transcriptional activity induced by LFA-3 was unaffected. Our data
      strongly suggest a selectivity in induction of nuclear factors by the CD2-LFA-3
      and CD28-B7-1 pathways. This selectivity may contribute to regulation of the
      levels of IL-2 induced by LFA-3 and B7-1 costimulation and favor autocrine and
      paracrine T-cell responses, respectively.

PMID- 9032259
TI  - Rac regulation of transformation, gene expression, and actin organization by
      multiple, PAK-independent pathways.
AB  - Rac1 and RhoA are members of the Rho family of Ras-related proteins and function
      as regulators of actin cytoskeletal organization, gene expression, and cell cycle
      progression. Constitutive activation of Rac1 and RhoA causes tumorigenic
      transformation of NIH 3T3 cells, and their functions may be required for full Ras
      transformation. The effectors by which Rac1 and RhoA mediate these diverse
      activities, as well as the interrelationship between these events, remain poorly
      understood. Rac1 is distinct from RhoA in its ability to bind and activate the
      p65 PAK serine/threonine kinase, to induce lamellipodia and membrane ruffling,
      and to activate the c-Jun NH2-terminal kinase (JNK). To assess the role of PAK in
      Rac1 function, we identified effector domain mutants of Rac1 and Rac1-RhoA
      chimeric proteins that no longer bound PAK. Surprisingly, PAK binding was
      dispensable for Rac1-induced transformation and lamellipodium formation, as well
      as activation of JNK, p38, and serum response factor (SRF). However, the ability
      of Rac1 to bind to and activate PAK correlated with its ability to stimulate
      transcription from the cyclin D1 promoter. Furthermore, Rac1 activation of JNK or
      SRF, or induction of lamellipodia, was neither necessary nor sufficient for Rac1
      transforming activity. Finally, the signaling pathways that mediate Rac1
      activation of SRF or JNK were distinct from those that mediate Rac1 induction of
      lamellipodia. Taken together, these observations suggest that Rac1 regulates at
      least four distinct effector-mediated functions and that multiple pathways may
      contribute to Rac1-induced cellular transformation.

PMID- 9032260
TI  - A severely defective TATA-binding protein-TFIIB interaction does not preclude
      transcriptional activation in vivo.
AB  - In yeast cells, mutations in the TATA-binding protein (TBP) that disrupt the
      interaction with the TATA element or with TFIIA can selectively impair the
      response to acidic activator proteins. We analyzed the transcriptional properties
      of TBP derivatives in which residues that directly interact with TFIIB were
      replaced by alanines. Surprisingly, a derivative with a 50-fold defect in TBP
      TFIIB-TATA complex formation in vitro (E188A) supports viability and responds
      efficiently to activators in vivo. The E186A derivative, which displays a 100
      fold defect in TBP-TFIIB-TATA complex formation, does not support viability, yet
      it does respond to activators. Conversely, the L189A mutation, which has the
      mildest effect on the interaction with TFIIB (10-fold), can abolish
      transcriptional activation and cell viability when combined with mutations on the
      DNA-binding surface. This "synthetic lethal" effect is not observed with E188A,
      suggesting that the previously described role of L189 in transcriptional
      activation may be related to its location on the DNA-binding surface and not to
      its interaction with TFIIB. Finally, when using TBP mutants defective on multiple
      interaction surfaces, we observed synthetic lethal effects between mutations on
      the TFIIA and TFIIB interfaces but found that mutations implicated in association
      with polymerase II and TFIIF did not have significant effects in vivo. Taken
      together, these results argue that, unlike the TBP-TATA and TBP-TFIIA
      interactions, the TBP-TFIIB interaction is not generally limiting for
      transcriptional activation in vivo.

PMID- 9032261
TI  - Lck regulates Vav activation of members of the Rho family of GTPases.
AB  - Vav is a member of a family of oncogene proteins that share an approximately 250
      amino-acid motif called a Dbl homology domain. Paradoxically, Dbl itself and
      other proteins containing a Dbl domain catalyze GTP-GDP exchange for Rho family
      proteins, whereas Vav has been reported to catalyze GTP-GDP exchange for Ras
      proteins. We present Saccharomyces cerevisiae genetic data, in vitro biochemical
      data, and animal cell biological data indicating that Vav is a guanine nucleotide
      exchange factor for Rho-related proteins, but in similar genetic and biochemical
      experiments we fail to find evidence that Vav is a guanine nucleotide exchange
      factor for Ras. Further, we present data indicating that the Lck kinase activates
      the guanine nucleotide exchange factor and transforming activity of Vav.

PMID- 9032262
TI  - Dbp3p, a putative RNA helicase in Saccharomyces cerevisiae, is required for
      efficient pre-rRNA processing predominantly at site A3.
AB  - In Saccharomyces cerevisiae, ribosomal biogenesis takes place primarily in the
      nucleolus, in which a single 35S precursor rRNA (pre-rRNA) is first transcribed
      and sequentially processed into 25S, 5.8S, and 18S mature rRNAs, leading to the
      formation of the 40S and 60S ribosomal subunits. Although many components
      involved in this process have been identified, our understanding of this
      important cellular process remains limited. Here we report that one of the
      evolutionarily conserved DEAD-box protein genes in yeast, DBP3, is required for
      optimal ribosomal biogenesis. DBP3 encodes a putative RNA helicase, Dbp3p, of 523
      amino acids in length, which bears a highly charged amino terminus consisting of
      10 tandem lysine-lysine-X repeats ([KKX] repeats). Disruption of DBP3 is not
      lethal but yields a slow-growth phenotype. This genetic depletion of Dbp3p
      results in a deficiency of 60S ribosomal subunits and a delayed synthesis of the
      mature 25S rRNA, which is caused by a prominent kinetic delay in pre-rRNA
      processing at site A3 and to a lesser extent at sites A2 and A0. These data
      suggest that Dbp3p may directly or indirectly facilitate RNase MRP cleavage at
      site A3. The direct involvement of Dbp3p in ribosomal biogenesis is supported by
      the finding that Dbp3p is localized predominantly in the nucleolus. In addition,
      we show that the [KKX] repeats are dispensable for Dbp3p's function in ribosomal
      biogenesis but are required for its proper localization. The [KKX] repeats thus
      represent a novel signaling motif for nuclear localization and/or retention.

PMID- 9032263
TI  - Frequent aberrant methylation of p16INK4a in primary rat lung tumors.
AB  - The p16INK4a (p16) tumor suppressor gene is frequently inactivated by homozygous
      deletion or methylation of the 5' CpG island in cell lines derived from human non
      small-cell lung cancers. However, the frequency of dysfunction in primary tumors
      appears to be significantly lower than that in cell lines. This discordance could
      result from the occurrence or selection of p16 dysfunction during cell culture.
      Alternatively, techniques commonly used to examine tumors for genetic and
      epigenetic alterations may not be sensitive enough to detect all dysfunctions
      within the heterogeneous cell population present in primary tumors. If p16
      inactivation plays a central role in development of non-small-cell lung cancer,
      then the frequency of gene inactivation in primary tumors should parallel that
      observed in cell lines. The present investigation addressed this issue in primary
      rat lung tumors and corresponding derived cell lines. A further goal was to
      determine whether the aberrant p16 gene methylation seen in human tumors is a
      conserved event in this animal model. The rat p16 gene was cloned and sequenced,
      and the predicted amino acid sequence of its product found to be 62% homologous
      to the amino acid sequence of the human analog. Homozygous deletion accounted for
      loss of p16 expression in 8 of 20 cell lines, while methylation of the CpG island
      extending throughout exon 1 was observed in 9 of 20 cell lines. 2-Deoxy-5
      azacytidine treatment of cell lines with aberrant methylation restored gene
      expression. The methylated phenotype seen in cell lines showed an absolute
      correlation with detection of methylation in primary tumors. Aberrant methylation
      was also detected in four of eight primary tumors in which the derived cell line
      contained a deletion in p16. These results substantiate the primary tumor as the
      origin for dysfunction of the p16 gene and implicate CpG island methylation as
      the major mechanism for inactivating this gene in the rat lung tumors examined.
      Furthermore, rat lung cancer appears to be an excellent model in which to
      investigate the mechanisms of de novo gene methylation and the role of p16
      dysfunction in the progression of neoplasia.

PMID- 9032264
TI  - Cloning of the novel human myeloid-cell-specific C/EBP-epsilon transcription
      factor.
AB  - Chicken NF-M transcription factor, in cooperation with either c-Myb or v-Myb, is
      active in the combinatorial activation of myeloid-cell-specific genes in
      heterologous cell types, such as embryonic fibroblasts. In humans, similar
      effects were observed with homologous members of the CCAAT/enhancer-binding
      protein (C/EBP) family of transcriptional regulators, especially the human
      homolog of chicken NF-M, C/EBP-beta (NF-IL6). However, the NF-IL6 gene is
      expressed in a variety of nonmyeloid cell types and is strongly inducible in
      response to inflammatory stimuli, making it an unlikely candidate to have an
      exclusive role as a combinatorial differentiation switch during myelopoiesis in
      human cells. By using a reverse transcription-PCR-based approach and a set of
      primers specific for the DNA-binding domains of highly homologous members of the
      C/EBP family of transcriptional regulators, we have cloned a novel human gene
      encoding a member of the C/EBP gene family, identified as the human homolog of
      CRP1, C/EBP-epsilon. A 1.2-kb cDNA encoding full-length human C/EBP-epsilon was
      cloned from a promyelocyte-late myeloblast-derived lambda gt11 library. Molecular
      analysis of the cDNA and genomic clones indicated the presence of two exons
      encoding a protein with an apparent molecular mass of 32 kDa and a pI of 9.5.
      Primer extension analysis of C/EBP-epsilon mRNA detected a single major
      transcription start site approximately 200 bp upstream of the start codon. The
      putative promoter area is similar to those of several other myeloid-cell-specific
      genes in that it contains no TATAAA box but has a number of purine-rich stretches
      with multiple sites for the factors of the Ets family of transcriptional
      regulators. Northern blot analyses indicated a highly restricted mRNA expression
      pattern, with the strongest expression occurring in promyelocyte and late
      myeloblast-like cell lines. Western blot and immunoprecipitation studies using
      rabbit anti-C/EBP-epsilon antibodies raised against the N-terminal portion of
      C/EBP-epsilon (amino acids 1 to 115) showed that C/EBP-epsilon is a 32-kDa
      nuclear phosphoprotein. The human C/EBP-epsilon protein exhibited strong and
      specific binding to double-stranded DNA containing consensus C/EBP sites.
      Cotransfection of the C/EBP-epsilon sense and antisense expression constructs
      together with chloramphenicol acetyltransferase reporter vectors containing
      myeloid-cell-specific c-mim and human myeloperoxidase promoters suggested a role
      for C/EBP-epsilon transcription factor in the regulation of a subset of myeloid
      cell-specific genes. Transient tranfection of a promyelocyte cell line (NB4) with
      a C/EBP-epsilon expression plasmid increased cell growth by sevenfold, while
      antisense C/EBP-epsilon caused a fivefold decrease in clonal growth of these
      cells.

PMID- 9032265
TI  - Transcriptional regulation of the ferritin heavy-chain gene: the activity of the
      CCAAT binding factor NF-Y is modulated in heme-treated Friend leukemia cells and
      during monocyte-to-macrophage differentiation.
AB  - The ferritin H-chain gene promoter regulation was analyzed in heme-treated Friend
      leukemia cells (FLCs) and during monocyte-to-macrophage differentiation. In the
      majority of cell lines studied, the regulation of ferritin expression was exerted
      mostly at the translational level. However, in differentiating erythroid cells,
      which must incorporate high levels of iron to sustain hemoglobin synthesis, and
      in macrophages, which are involved in iron storage, transcriptional regulation
      seemed to be a relevant mechanism. We show here that the minimum region of the
      ferritin H-gene promoter that is able to confer transcriptional regulation by
      heme in FLCs to a reporter gene is 77 nucleotides upstream of the TATA box. This
      cis element binds a protein complex referred to as HRF (heme-responsive factor),
      which is greatly enhanced both in heme-treated FLCs and during monocyte-to
      macrophage differentiation. The CCAAT element present in reverse orientation in
      this promoter region of the ferritin H-chain gene is necessary for binding and
      for gene activity, since a single point mutation is able to abolish the binding
      of HRF and the transcriptional activity in transfected cells. By competition
      experiments and supershift assays, we identified the induced HRF as containing at
      least the ubiquitous transcription factor NF-Y. NF-Y is formed by three subunits,
      A, B, and C, all of which are necessary for DNA binding. Cotransfection with a
      transdominant negative mutant of the NF-YA subunit abolishes the transcriptional
      activation by heme, indicating that NF-Y plays an essential role in this
      activation. We have also observed a differential expression of the NF-YA subunit
      in heme-treated and control FLCs and during monocyte-to-macrophage
      differentiation.

PMID- 9032267
TI  - The transcriptional integrator CREB-binding protein mediates positive cross talk
      between nuclear hormone receptors and the hematopoietic bZip protein p45/NF-E2.
AB  - Thyroid hormone (T3) and retinoic acid (RA) play important roles in
      erythropoiesis. We found that the hematopoietic cell-specific bZip protein p45/NF
      E2 interacts with T3 receptor (TR) and RA receptor (RAR) but not retinoid X
      receptor. The interaction is between the DNA-binding domain of the nuclear
      receptor and the leucine zipper region of p45/NF-E2 but is markedly enhanced by
      cognate ligand. Remarkably, ligand-dependent transactivation by TR and RAR is
      markedly potentiated by p45/NF-E2. This effect of p45/NF-E2 is prevented by maf
      like protein p18, which functions positively as a heterodimer with p45/NF-E2 on
      DNA. Potentiation of hormone action by p45/NF-E2 requires its activation domain,
      which interacts strongly with the multifaceted coactivator cyclic AMP response
      element protein-binding protein (CBP). The region of CBP which interacts with
      p45/NF-E2 is the same interaction domain that mediates inhibition of hormone
      stimulated transcription by AP1 transcription factors. Overexpression of the bZip
      interaction domain of CBP specifically abolishes the positive cross talk between
      TR and p45/NF-E2. Thus, positive cross talk between p45/NF-E2 and nuclear hormone
      receptors requires direct protein-protein interactions between these factors and
      with CBP, whose integration of positive signals from two transactivation domains
      provides a novel mechanism for potentiation of hormone action in hematopoietic
      cells.

PMID- 9032266
TI  - Cloning and characterization of Ras-GRF2, a novel guanine nucleotide exchange
      factor for Ras.
AB  - Conversion of Ras proteins into an activated GTP-bound state able to bind
      effector proteins is catalyzed by specific guanine nucleotide exchange factors in
      response to a large number of extracellular stimuli. Here we report the isolation
      of mouse cDNAs encoding Ras-GRF2, a multidomain 135-kDa protein containing a COOH
      terminal Cdc25-related domain that stimulates release of GDP from Ras but not
      other GTPases in vitro. Ras-GRF2 bound specifically to immobilized Ras lacking
      bound nucleotides, suggesting stabilization of the nucleotide-free form of Ras as
      a mechanism of catalyzing nucleotide exchange. The NH2-terminal region of Ras
      GRF2 is predicted to contain features common to various signaling proteins
      including two pleckstrin homology domains and a Dbl homology region. Ras-GRF2
      also contains an IQ motif which was required for its apparent constitutive
      association with calmodulin in epithelial cells ectopically expressing Ras-GRF2.
      Transient expression of Ras-GRF2 in kidney epithelial cells stimulated GTP
      binding by Ras and potentiated calcium ionophore-induced activation of mitogen
      activated protein kinase (ERK1) dependent upon the IQ motif. Calcium influx
      caused Ras-GRF2 subcellular localization to change from cytosolic to peripheral,
      suggesting a possible mechanism for controlling Ras-GRF2 interactions with Ras at
      the plasma membrane. Epithelial cells overexpressing Ras-GRF2 are morphologically
      transformed and grow in a disorganized manner with minimal intercellular
      contacts. Northern analysis indicated a 9-kb GRF2 transcript in brain and lung,
      where p135 Ras-GRF2 is known to be expressed, and RNAs of 12 kb and 2.2 kb were
      detected in several tissues. Thus, Ras-GRF2 proteins with different domain
      structures may be widely expressed and couple diverse extracellular signals to
      Ras activation.

PMID- 9032268
TI  - Cell transformation mediated by homodimeric E2A-HLF transcription factors.
AB  - The E2A-HLF fusion gene, created by the t(17;19)(q22;p13) chromosomal
      translocation in pro-B lymphocytes, encodes an oncogenic protein in which the E2A
      trans-activation domain is linked to the DNA-binding and protein dimerization
      domain of hepatic leukemia factor (HLF), a member of the proline- and acidic
      amino acid-rich (PAR) subfamily of bZIP transcription factors. This fusion
      product binds to its DNA recognition site not only as a homodimer but also as a
      heterodimer with HLF and two other members of the PAR bZIP subfamily, thyrotroph
      embryonic factor (TEF) and albumin promoter D-box binding protein (DBP). Thus,
      E2A-HLF could transform cells by direct regulation of downstream target genes,
      acting through homodimeric or heterodimeric complexes, or by sequestering normal
      PAR proteins into nonfunctional heterocomplexes (dominant-negative interference).
      To distinguish among these models, we constructed mutant E2A-HLF proteins in
      which the leucine zipper domain of HLF was extended by one helical turn or
      altered in critical charged amino acids, enabling the chimera to bind to DNA as a
      homodimer but not as a heterodimer with HLF or other PAR proteins. When
      introduced into NIH 3T3 cells in a zinc-inducible vector, each of these mutants
      induced anchorage-independent growth as efficiently as unaltered E2A-HLF,
      indicating that the chimeric oncoprotein can transform cells in its homodimeric
      form. Transformation also depended on an intact E2A activator region, providing
      further support for a gain-of-function contribution to oncogenesis rather than
      one based on a dominant-interfering or dominant-negative mechanism. Thus, the
      tumorigenic effects of E2A-HLF and its mutant forms in NIH 3T3 cells favor a
      straightforward model in which E2A-HLF homodimers bind directly to
      promoter/enhancer elements of downstream target genes and alter their patterns of
      expression in early B-cell progenitors.

PMID- 9032269
TI  - Evidence for DNA-PK-dependent and -independent DNA double-strand break repair
      pathways in mammalian cells as a function of the cell cycle.
AB  - Mice homozygous for the scid (severe combined immune deficiency) mutation are
      defective in the repair of DNA double-strand breaks (DSBs) and are consequently
      very X-ray sensitive and defective in the lymphoid V(D)J recombination process.
      Recently, a strong candidate for the scid gene has been identified as the
      catalytic subunit of the DNA-dependent protein kinase (DNA-PK) complex. Here, we
      show that the activity of the DNA-PK complex is regulated in a cell cycle
      dependent manner, with peaks of activity found at the G1/early S phase and again
      at the G2 phase in wild-type cells. Interestingly, only the deficit of the
      G1/early S phase DNA-PK activity correlated with an increased hypersensitivity to
      X-irradiation and a DNA DSB repair deficit in synchronized scid pre-B cells.
      Finally, we demonstrate that the DNA-PK activity found at the G2 phase may be
      required for exit from a DNA damage-induced G2 checkpoint arrest. These
      observations suggest the presence of two pathways (DNA-PK-dependent and 
      independent) of illegitimate mammalian DNA DSB repair and two distinct roles (DNA
      DSB repair and G2 checkpoint traversal) for DNA-PK in the cellular response to
      ionizing radiation.

PMID- 9032270
TI  - Phosphorylation of the RNA polymerase II largest subunit during Xenopus laevis
      oocyte maturation.
AB  - Xenopus laevis oogenesis is characterized by an active transcription which ceases
      abruptly upon maturation. To survey changes in the characteristics of the
      transcriptional machinery which might contribute to this transcriptional arrest,
      the phosphorylation status of the RNA polymerase II largest subunit (RPB1
      subunit) was analyzed during oocyte maturation. We found that the RPB1 subunit
      accumulates in large quantities from previtellogenic early diplotene oocytes up
      to fully grown oocytes. The C-terminal domain (CTD) of the RPB1 subunit was
      essentially hypophosphorylated in growing oocytes from Dumont stage IV to stage
      VI. Upon maturation, the proportion of hyperphosphorylated RPB1 subunits
      increased dramatically and abruptly. The hyperphosphorylated RPB1 subunits were
      dephosphorylated within 1 h after fertilization or heat shock of the matured
      oocytes. Extracts from metaphase II-arrested oocytes showed a much stronger CTD
      kinase activity than extracts from prophase stage VI oocytes. Most of this kinase
      activity was attributed to the activated Xp42 mitogen-activated protein (MAP)
      kinase, a MAP kinase of the ERK type. Making use of artificial maturation of the
      stage VI oocyte through microinjection of a recombinant stable cyclin B1, we
      observed a parallel activation of Xp42 MAP kinase and phosphorylation of RPB1.
      Both events required protein synthesis, which demonstrated that activation of
      p34(cdc2)off kinase was insufficient to phosphorylate RPB1 ex vivo and was
      consistent with a contribution of the Xp42 MAP kinase to RPB1 subunit
      phosphorylation. These results further support the possibility that the largest
      RNA polymerase II subunit is a substrate of the ERK-type MAP kinases during
      oocyte maturation, as previously proposed during stress or growth factor
      stimulation of mammalian cells.

PMID- 9032271
TI  - Characterization of a mutant cell line that does not activate NF-kappaB in
      response to multiple stimuli.
AB  - Numerous genes required during the immune or inflammation response as well as the
      adhesion process are regulated by nuclear factor kappaB (NF-kappaB). Associated
      with its inhibitor, I kappaB, NF-kappaB resides as an inactive form in the
      cytoplasm. Upon stimulation by various agents, I kappaB is proteolyzed and NF
      kappaB translocates to the nucleus, where it activates its target genes. The
      transduction pathways that lead to I kappaB inactivation remain poorly
      understood. In this study, we have characterized a cellular mutant, the 70/Z3
      derived 1.3E2 murine pre-B cell line, that does not activate NF-kappaB in
      response to several stimuli. We demonstrate that upon stimulation by
      lipopolysaccharide, Taxol, phorbol myristate acetate, interleukin-1, or double
      stranded RNA, I kappaB alpha is not degraded, as a result of an absence of
      induced phosphorylation on serines 32 and 36. Neither a mutation in I kappaB
      alpha nor a mutation in p50 or relA, the two major subunits of NF-kappaB in this
      cell line, accounts for this phosphorylation defect. As well as culminating in
      the inducible phosphorylation of I kappaB alpha on serines 32 and 36, all the
      stimuli that are inactive on 1.3E2 cells exhibit a sensitivity to the antioxidant
      pyrrolidine dithiocarbamate (PDTC). In contrast, stimuli such as hyperosmotic
      shock or phosphatase inhibitors, which use PDTC-insensitive pathways, induce I
      kappaB alpha degradation in 1.3E2. Analysis of the redox status of 1.3E2 does not
      reveal any difference from wild-type 70Z/3. We also report that the human T-cell
      leukemia virus type 1 (HTLV-1)-derived Tax trans-activator induces NF-kappaB
      activity in 1.3E2, suggesting that this viral protein does not operate via the
      defective pathway. Finally, we show that two other I kappaB molecules, I kappaB
      beta and the recently identified I kappaB epsilon, are not degraded in the 1.3E2
      cell line following stimulation. Our results demonstrate that 1.3E2 is a cellular
      transduction mutant exhibiting a defect in a step that is required by several
      different stimuli to activate NF-kappaB. In addition, this analysis suggests a
      common step in the signaling pathways that trigger I kappaB alpha, I kappaB beta,
      and I kappaB epsilon degradation.

PMID- 9032272
TI  - Cyclic AMP-dependent protein kinase inhibits ADH2 expression in part by
      decreasing expression of the transcription factor gene ADR1.
AB  - In Saccharomyces cerevisiae, the unregulated cyclic AMP-dependent protein kinase
      (cAPK) activity of bcy1 mutant cells inhibits expression of the glucose
      repressible ADH2 gene. The transcription factor Adr1p is thought to be the
      primary target of cAPK. Here we demonstrate that the decreased abundance of Adr1p
      in bcy1 mutant cells contributes to the inhibition of ADH2 expression. Activation
      of ADH2 transcription was blocked in bcy1 mutant cells, and UAS1, the Adr1p
      binding site in the ADH2 promoter, was sufficient to mediate this effect.
      Concurrent with this loss of transcriptional activation was an up to 30-fold
      reduction in the level of Adr1p. Mutating the strong cAPK phosphorylation site at
      serine 230 did not suppress this effect. Analysis of ADR1 mRNA levels and ADR1
      lacZ expression suggested that decreased ADR1 transcription was responsible for
      the reduced protein level. In contrast to the ADH2 promoter, however, deletion
      analysis suggested that cAPK does not act through a discrete DNA element in the
      ADR1 promoter. The amount of Adr1p found in bcy1 mutant cells should have been
      sufficient to support 23% of the wild-type level of ADH2 expression. Since no
      ADH2 expression was detectable in bcy1 mutant cells, cAPK must also act by other
      mechanisms. Overexpression of Adr1p only partially restored ADH2 expression,
      indicating that some of these mechanisms may impinge upon events at or subsequent
      to the ADR1-dependent step in ADH2 transcriptional activation.

PMID- 9032273
TI  - Identification of downstream-initiated c-Myc proteins which are dominant-negative
      inhibitors of transactivation by full-length c-Myc proteins.
AB  - The c-myc gene has been implicated in multiple cellular processes including
      proliferation, differentiation, and apoptosis. In addition to the full-length c
      Myc 1 and 2 proteins, we have found that human, murine, and avian cells express
      smaller c-Myc proteins arising from translational initiation at conserved
      downstream AUG codons. These c-Myc short (c-Myc S) proteins lack most of the N
      terminal transactivation domain but retain the C-terminal protein dimerization
      and DNA binding domains. As with full-length c-Myc proteins, the c-Myc S proteins
      appear to be localized to the nucleus, are relatively unstable, and are
      phosphorylated. Significant levels of c-Myc S, often approaching the levels of
      full-length c-Myc, are transiently observed during the rapid growth phase of
      several different types of cells. Optimization of the upstream initiation codons
      resulted in greatly reduced synthesis of the c-Myc S proteins, suggesting that a
      "leaky scanning" mechanism leads to the translation of these proteins. In some
      hematopoietic tumor cell lines having altered c-myc genes, the c-Myc S proteins
      are constitutively expressed at levels equivalent to that of full-length c-Myc.
      As predicted, the c-Myc S proteins are unable to activate transcription and
      inhibited transactivation by full-length c-Myc proteins, suggesting a dominant
      negative inhibitory function. While these transcriptional inhibitors would not be
      expected to function as full-length c-Myc, the occurrence of tumors which express
      constitutive high levels of c-Myc S and their transient synthesis during rapid
      cell growth suggest that these proteins do not interfere with the growth
      promoting functions of full-length c-Myc.

PMID- 9032274
TI  - Methylation of genomes and genes at the invertebrate-vertebrate boundary.
AB  - Patterns of DNA methylation in animal genomes are known to vary from an apparent
      absence of modified bases, via methylation of a minor fraction of the genome, to
      genome-wide methylation. Representative genomes from 10 invertebrate phyla
      comprise predominantly nonmethylated DNA and (usually but not always) a minor
      fraction of methylated DNA. In contrast, all 27 vertebrate genomes that have been
      examined display genome-wide methylation. Our studies of chordate genomes suggest
      that the transition from fractional to global methylation occurred close to the
      origin of vertebrates, as amphioxus has a typically invertebrate methylation
      pattern whereas primitive vertebrates (hagfish and lamprey) have patterns that
      are typical of vertebrates. Surprisingly, methylation of genes preceded this
      transition, as many invertebrate genes have turned out to be heavily methylated.
      Methylation does not preferentially affect genes whose expression is highly
      regulated, as several housekeeping genes are found in the heavily methylated
      fraction whereas several genes expressed in a tissue-specific manner are in the
      nonmethylated fraction.

PMID- 9032275
TI  - DAX-1 inhibits SF-1-mediated transactivation via a carboxy-terminal domain that
      is deleted in adrenal hypoplasia congenita.
AB  - X-linked adrenal hypoplasia congenita (AHC) with hypogonadotropic hypogonadism
      was recently shown to be caused by mutations in a gene referred to as DAX-1,
      which encodes a novel member of the orphan nuclear receptor family. DAX-1 is
      homologous to other nuclear receptors in its carboxy-terminal region, but it
      lacks the characteristic zinc finger DNA-binding domain. The tissue distribution
      of DAX-1 (adrenal cortex, gonads, hypothalamus, and pituitary) is the same as
      that of another orphan nuclear receptor, steroidogenic factor 1 (SF-1), that is
      required for development of the adrenal glands and gonads. We examined whether
      DAX-1 and SF-1 might interact in the regulation of SF-1-responsive target genes.
      Coexpression of DAX-1 and SF-1 inhibited SF-1-mediated transactivation. DAX-1 was
      shown to interact directly with SF-1 in in vitro protein binding studies;
      however, it did not interfere with SF-1 binding to DNA in gel mobility shift
      assays. Transactivation by GAL4-SF-1 constructs was inhibited by DAX-1,
      indicating that neither the SF-1 DNA-binding domain nor the SF-1 binding sites
      are required for inhibition by DAX-1. A series of DAX-1 deletion mutants
      localized the inhibitory domain to the carboxy-terminal region of the protein.
      Deletion of this domain also reduced basal transcriptional silencing by GAL4-DAX
      1. This inhibitory domain has been deleted in all naturally occurring AHC
      deletion mutants described to date. In addition, two naturally occurring point
      mutations in DAX-1 exhibited impaired inhibition of SF-1. We conclude that DAX-1
      can inhibit SF-1 transcriptional activity and suggest that the loss of this
      inhibitory property in DAX-1 may account in part for the phenotype of AHC.

PMID- 9032276
TI  - Incubation at the nonpermissive temperature induces deficiencies in UV resistance
      and mutagenesis in mouse mutant cells expressing a temperature-sensitive
      ubiquitin-activating enzyme (E1).
AB  - In temperature-sensitive (ts) mutants of mouse FM3A cells, the levels of
      mutagenesis and survival of cells treated with DNA-damaging agents have been
      difficult to assess because they are killed after their mutant phenotypes are
      expressed at the nonpermissive temperature. To avoid this difficulty, we
      incubated the ts mutant cells at the restrictive temperature, 39 degrees C, for
      only a limited period after inducing DNA damage. We used ts mutants defective in
      genes for ubiquitin-activating enzyme (E1), DNA polymerase alpha, and p34(cdc2)
      kinase. Whereas the latter two showed no effect, E1 mutants were sensitized
      remarkably to UV light if incubated at 39 degrees C for limited periods after UV
      exposure. Eighty-five percent of the sensitization occurred within the first 12 h
      of incubation at 39 degrees C, and more than 36 h at 39 degrees C did not produce
      any further sensitization. Moreover, while the 39 degrees C incubation gave E1
      mutants a moderate spontaneous mutator phenotype, the same treatment
      significantly diminished the level of UV-induced 6-thioguanine resistance
      mutagenesis and extended the time necessary for expression of the mutation
      phenotype. These characteristics of E1 mutants are reminiscent of the defective
      DNA repair phenotypes of Saccharomyces cerevisiae rad6 mutants, which have
      defects in a ubiquitin-conjugating enzyme (E2), to which E1 is known to transfer
      ubiquitin. These results demonstrate the involvement of E1 in eukaryotic DNA
      repair and mutagenesis and provide the first direct evidence that the ubiquitin
      conjugation system contributes to DNA repair in mammalian cells.

PMID- 9032277
TI  - bic, a novel gene activated by proviral insertions in avian leukosis virus
      induced lymphomas, is likely to function through its noncoding RNA.
AB  - The bic locus is a common retroviral integration site in avian leukosis virus
      (ALV)-induced B-cell lymphomas originally identified by infection of chickens
      with ALVs of two different subgroups (Clurman and Hayward, Mol. Cell. Biol.
      9:2657-2664, 1989). Based on its frequent association with c-myc activation and
      its preferential activation in metastatic tumors, the bic locus is thought to
      harbor a gene that can collaborate with c-myc in lymphomagenesis and presumably
      plays a role in late stages of tumor progression. In the present study, we have
      cloned and characterized two novel genes, bdw and bic, at the bic locus. bdw
      encoded a putative novel protein of 345 amino acids. However, its expression did
      not appear to be altered in tumor tissues, suggesting that it is not involved in
      oncogenesis. The bic gene consisted of two exons and was expressed as two spliced
      and alternatively polyadenylated transcripts at low levels in
      lymphoid/hematopoietic tissues. In tumors harboring bic integrations, proviruses
      drove bic gene expression by promoter insertion, resulting in high levels of
      expression of a chimeric RNA containing bic exon 2. Interestingly, bic lacked an
      extensive open reading frame, implying that it may function through its RNA.
      Computer analysis of RNA from small exon 2 of bic predicted extensive double
      stranded structures, including a highly ordered RNA duplex between nucleotides
      316 and 461. The possible role of bic in cell growth and differentiation is
      discussed in view of the emerging evidence that untranslated RNAs play a role in
      growth control.

PMID- 9032278
TI  - E2a-Pbx1 induces aberrant expression of tissue-specific and developmentally
      regulated genes when expressed in NIH 3T3 fibroblasts.
AB  - The E2a-Pbx1 oncoprotein contains the transactivation domain of E2a joined to the
      DNA-binding homeodomain (HD) of Pbx1. In mice, E2a-Pbx1 transforms T lymphoblasts
      and fibroblasts and blocks myeloblast differentiation. Pbx1 and E2a-Pbx1 bind DNA
      as heterodimers with other HD proteins whose expression is tissue specific. While
      the transactivation domain of E2a is required for all forms of transformation,
      DNA binding by the Pbx1 HD is essential for blocking myeloblast differentiation
      but dispensable for fibroblast or T-lymphoblast transformation. These properties
      suggest (i) that E2a-Pbx1 causes cellular transformation by activating gene
      transcription, (ii) that transcription of E2a-Pbx1 target genes is normally
      regulated by ubiquitous Pbx proteins and tissue-specific partners, and (iii) that
      DNA-binding mutants of E2a-Pbx1 activate a subset of all gene targets. To test
      these predictions, genes induced in NIH 3T3 fibroblasts by E2a-Pbx1 were
      identified and examined for tissue- and stage-specific expression and their
      differential abilities to be upregulated by E2a-Pbx1 in NIH 3T3 fibroblasts and
      myeloblasts and by a DNA-binding mutant of E2a-Pbx1 in NIH 3T3 cells. Of 12 RNAs
      induced by E2a-Pbx1, 4 encoded known proteins (a J-C region of the immunoglobulin
      kappa light chain, natriuretic peptide receptor C, mitochondrial fumarase, and
      the 3',5'-cyclic nucleotide phosphodiesterase, PDE1A) and 5 encoded new proteins
      related to angiogenin, ion channels, villin, epidermal growth factor repeat
      proteins, and the human 2.19 gene product. Expression of many of these genes was
      tissue specific or developmentally regulated, and most were not expressed in
      fibroblasts, indicating that E2a-Pbx1 can induce ectopic expression of genes
      associated with lineage-specific differentiation.

PMID- 9032279
TI  - Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1
      deficient cells.
AB  - Mice made insulin receptor substrate 1 (IRS-1) deficient by targeted gene
      knockout exhibit growth retardation and abnormal glucose metabolism due to
      resistance to the actions of insulin-like growth factor 1 (IGF-1) and insulin (E.
      Araki et al., Nature 372:186-190, 1994; H. Tamemoto et al., Nature 372:182-186,
      1994). Embryonic fibroblasts and 3T3 cell lines derived from IRS-1-deficient
      embryos exhibit no IGF-1-stimulated IRS-1 phosphorylation or IRS-1-associated
      phosphatidylinositol 3-kinase (PI 3-kinase) activity but exhibit normal
      phosphorylation of IRS-2 and Shc and normal IRS-2-associated PI 3-kinase
      activity. IRS-1 deficiency results in a 70 to 80% reduction in IGF-1-stimulated
      cell growth and parallel decreases in IGF-1-stimulated S-phase entry, PI 3-kinase
      activity, and induction of the immediate-early genes c-fos and egr-1 but
      unaltered activation of the mitogen-activated protein kinases ERK 1 and ERK 2.
      Expression of IRS-1 in IRS-1-deficient cells by retroviral gene transduction
      restores IGF-1-stimulated mitogenesis, PI 3-kinase activation, and c-fos and egr
      1 induction in proportion to the level of reconstitution. Increasing the level of
      IRS-2 in these cells by using a retrovirus reconstitutes IGF-1 activation of PI 3
      kinase and immediate-early gene expression to the same degree as expression of
      IRS-1; however, IRS-2 overexpression has only a minor effect on IGF-1 stimulation
      of cell cycle progression. These results indicate that IRS-1 is not necessary for
      activation of ERK 1 and ERK 2 and that activation of ERK 1 and ERK 2 is not
      sufficient for IGF-1-stimulated activation of c-fos and egr-1. These data also
      provide evidence that IRS-1 and IRS-2 are not functionally interchangeable
      signaling intermediates for stimulation of mitogenesis despite their highly
      conserved structure and many common functions such as activating PI 3-kinase and
      early gene expression.

PMID- 9032280
TI  - Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2
      (Th2) cells but not in Th1 cells.
AB  - Transcriptional factors of the NFAT family play an important role in regulating
      the expression of several cytokine genes during the immune response, such as the
      genes for interleukin 2 (IL-2) and IL-4, among others. Upon antigen stimulation,
      precursor CD4+ T helper (pTh) cells proliferate and differentiate into two
      populations of effector cells (eTh1 and eTh2), each one expressing a specific
      pattern of cytokines that distinguishes them from their precursors. eTh2 cells
      are the major source of IL-4, while gamma interferon is produced by eTh1 cells.
      Here we have used reporter transgenic mice to show that DNA binding and
      transcriptional activities of NFAT are transiently induced during the
      differentiation of pTh cells into either eTh1 or eTh2 cells to mediate the
      expression of IL-2 as a common growth factor in both pathways. However, although
      NFAT DNA binding is similarly induced in both eTh1 and eTh2 cells upon antigen
      stimulation, only the NFAT complexes present in eTh2 cells are able to mediate
      high-level transcription, and relatively little NFAT transcriptional activity was
      induced in eTh1 cells. In contrast to activated pTh cells, neither eTh1 nor eTh2
      cells produced significant IL-2 upon stimulation, but the high levels of NFAT
      transcriptional activities directly correlate with the IL-4 production induced in
      response to antigen stimulation in eTh2 cells. These data suggest that activated
      NFAT is involved in the effector function of eTh2 cells and that the failure of
      eTh1 cells to produce IL-4 in response to an antigen is due, at least partially,
      to a failure to induce high-level transcription of the IL-4 gene by NFAT.
      Regulation of NFAT could be therefore a critical element in the polarization to
      eTh1 or eTh2.

PMID- 9032281
TI  - Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and
      TRAF2.
AB  - CD30 is a lymphoid cell-specific surface receptor which was originally identified
      as an antigen expressed on Hodgkin's lymphoma cells. Activation of CD30 induces
      the nuclear factor kappaB (NF-kappaB) transcription factor. In this study, we
      define the domains in CD30 which are required for NF-kappaB activation. Two
      separate elements of the cytoplasmic domain which were capable of inducing NF
      kappaB independently of one another were identified. The first domain (domain 1)
      mapped to a approximately 120-amino-acid sequence in the membrane-proximal region
      of the CD30 cytoplasmic tail, between residues 410 and 531. A second, more
      carboxy-terminal region (domain 2) was identified between residues 553 and 595.
      Domain 2 contains two 5- to 10-amino-acid elements which can mediate the binding
      of CD30 to members of the tumor necrosis factor receptor-associated factor (TRAF)
      family of signal transducing proteins. Coexpression of CD30 with TRAF1 or TRAF2
      but not TRAF3 augmented NF-kappaB activation through domain 2 but not domain 1.
      NF-kappaB induction through domain 2 was inhibited by coexpression of either full
      length TRAF3 or dominant negative forms of TRAF1 or TRAF2. In contrast, NF-kappaB
      induction by domain 1 was not affected by alterations in TRAF protein levels.
      Together, these data support a model in which CD30 can induce NF-kappaB by both
      TRAF-dependent and -independent mechanisms. TRAF-dependent induction of NF-kappaB
      appears to be regulated by the relative levels of individual TRAF proteins in the
      cell.

PMID- 9032282
TI  - Genes encoding farnesyl cysteine carboxyl methyltransferase in
      Schizosaccharomyces pombe and Xenopus laevis.
AB  - The mam4 mutation of Schizosaccharomyces pombe causes mating deficiency in h-
      cells but not in h+ cells. h- cells defective in mam4 do not secrete active
      mating pheromone M-factor. We cloned mam4 by complementation. The mam4 gene
      encodes a protein of 236 amino acids, with several potential membrane-spanning
      domains, which is 44% identical with farnesyl cysteine carboxyl methyltransferase
      encoded by STE14 and required for the modification of a-factor in Saccharomyces
      cerevisiae. Analysis of membrane fractions revealed that mam4 is responsible for
      the methyltransferase activity in S. pombe. Cells defective in mam4 produced
      farnesylated but unmethylated cysteine and small peptides but no intact M-factor.
      These observations strongly suggest that the mam4 gene product is farnesyl
      cysteine carboxyl methyltransferase that modifies M-factor. Furthermore,
      transcomplementation of S. pombe mam4 allowed us to isolate an apparent homolog
      of mam4 from Xenopus laevis (Xmam4). In addition to its sequence similarity to S.
      pombe mam4, the product of Xmam4 was shown to have a farnesyl cysteine carboxyl
      methyltransferase activity in S. pombe cells. The isolation of a vertebrate gene
      encoding farnesyl cysteine carboxyl methyltransferase opens the way to in-depth
      studies of the role of methylation in a large body of proteins, including Ras
      superfamily proteins.

PMID- 9032283
TI  - Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription.
AB  - Adipocyte differentiation is thought to involve sequential induction of the
      transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma
      (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and
      sufficient for adipocyte differentiation. Here we report that ectopic expression
      of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis
      and that retinoic acid (RA) completely inhibits adipogenesis by either form of
      C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta
      induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In
      transient transfection studies, liganded RA receptor (RAR) specifically blocks
      transcriptional activation by either C/EBPalpha or C/EBPbeta. These results
      strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte
      differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta
      mediated induction of downstream genes.

PMID- 9032284
TI  - Mutation in the Jak kinase JH2 domain hyperactivates Drosophila and mammalian Jak
      Stat pathways.
AB  - The Jak (Janus) family of nonreceptor tyrosine kinases plays a critical role in
      cytokine signal transduction pathways. In Drosophila melanogaster, the dominant
      hop(Tum-l) mutation in the Hop Jak kinase causes leukemia-like and other
      developmental defects. Previous studies have suggested that the Hop(Tum-l)
      protein might be a hyperactive kinase. Here, we report on the new dominant
      mutation hop(T42), which causes abnormalities that are similar to but more
      extreme than those caused by hop(Tum-l). We determined that Hop(T42) contains a
      glutamic acid-to-lysine substitution at amino acid residue 695 (E695K). This
      residue occurs in the JH2 (kinase-like) domain and is conserved among all Jak
      family members. We determined that Hop(Tum-1) and Hop(T42) both
      hyperphosphorylated and hyperactivated D-Stat when overexpressed in Drosophila
      cells. Moreover, we found that the hop(T42) phenotype was partially rescued by a
      reduction of wild-type D-stat activity. Finally, generation of the corresponding
      E695K mutation in murine Jak2 resulted in increased autophosphorylation and
      increased activation of Stat5 in COS cells. These results demonstrate that the
      mutant Hop proteins do indeed have increased tyrosine kinase activity, that the
      mutations hyperactivate the Hop-D-Stat pathway, and that Drosophila is a relevant
      system for the functional dissection of mammalian Jak-Stat pathways. Finally, we
      propose a model for the role of the Hop-D-Stat pathway in Drosophila
      hematopoiesis.

PMID- 9032286
TI  - Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated
      mRNA decay pathway.
AB  - Rapid turnover of nonsense-containing mRNAs in Saccharomyces cerevisiae is
      dependent on Upf1p, Nmd2p, and Upf3p, the products of the UPF1, NMD2/UPF2, and
      UPF3 genes, respectively. We showed previously that Upf1p and Nmd2p interact and
      that this interaction is required for nonsense-mediated mRNA decay (F. He and A.
      Jacobson, Genes Dev. 9:437-454, 1995; F. He, A. H. Brown, and A. Jacobson, RNA
      2:153-170, 1996). In this study we have used the yeast two-hybrid system to
      define other protein-protein interactions among the essential components of this
      decay pathway. Nmd2p-Upf3p and Upf1p-Upf3p interactions were identified, and the
      respective domains involved in these interactions were delineated by deletion
      analysis. The domains of Upf1p and Upf3p putatively involved in their mutual
      interaction were found to correspond to the domains on the two proteins which
      interact with Nmd2p, suggesting that Nmd2p bridges Upf1p and Upf3p. This
      conclusion was reinforced by experiments showing that: (i) deletion of NMD2
      completely abolishes interactions between Upf1p and Upf3p and (ii) overexpression
      of full-length Nmd2p or Nmd2p fragments that retain Upf1p- and Upf3p-interacting
      domains promotes 10- to 200-fold enhancement of Upf1p-Nmd2p-Upf3p complex
      formation. These results; the observation that cells harboring either single or
      multiple deletions of UPF1, NMD2, and UPF3 inhibit nonsense-mediated mRNA decay
      to the same extent; and an analysis of the possible targets of a dominant
      negative NMD2 allele indicate that Upf1p, Nmd2p, Upf3p, and at least one other
      factor are functionally dependent, interacting components of the yeast nonsense
      mediated mRNA decay pathway.

PMID- 9032285
TI  - Differential binding of the Bombyx silk gland-specific factor SGFB to its target
      DNA sequence drives posterior-cell-restricted expression.
AB  - The gene encoding the silk protein P25 in Bombyx mori is expressed in the
      posterior silk gland (PSG) cells and repressed in the middle silk gland (MSG)
      cells. To identify the factors involved in this transcription-dependent spatial
      restriction, we examined the P25 chromatin in PSG and MSG nuclei by DNase I-aided
      ligation-mediated PCR and analyzed the expression of various P25-lacZ constructs
      in biolistically treated silk glands. P25 promoter activation depends on two cis
      acting elements. One coincides with the target sequence of SGFB, a silk gland
      specific factor present in all silk gland nuclei, but bound to its target DNA
      sequence in only PSG cells. The interaction of the other element with a factor
      that we named PSGF is also exclusive to PSG cells. Placed ahead of a non-P25
      related basal promoter, the SGFB and PSGF elements are sufficient to drive
      posterior-cell transcription. Collectively, our data support the hypothesis that
      the spatial restriction of P25 expression is driven by the stabilization of SGFB
      onto its target sequence by the action of PSGF.

PMID- 9032288
TI  - A globin enhancer acts by increasing the proportion of erythrocytes expressing a
      linked transgene.
AB  - Enhancer elements have been shown to affect the probability of a gene
      establishing an active transcriptional state and suppress the silencing of
      reporter genes in cell lines, but their effect in transgenic mice has been
      obscured by the use of assays that do not assess expression on a cell-by-cell
      basis. We have examined the effect of a globin enhancer on the variegation of
      lacZ expression in erythrocytes of transgenic mice. Mice carrying lacZ driven by
      the alpha-globin promoter exhibit beta-galactosidase (beta-Gal) expression in
      only a very small proportion of embryonic erythrocytes. When the transgenic
      construct also contains the (alphaHS-40 enhancer, which controls expression of
      the alpha-globin gene, expression is seen in a high proportion of embryonic
      erythrocytes, although there are variations between transgenic lines which can be
      attributed to different sites of integration. Analysis of beta-Gal expression
      levels suggests that expressing cells in lines carrying only the alpha-globin
      promoter express as much beta-Gal as those in which the transgene also contains
      alphaHS-40. A marked decline in transgene expression occurs as mice age, which is
      mainly due to a decrease in the proportion of cells expressing the transgene.
      Thus, a globin enhancer can act to suppress variegation of a linked transgene;
      this result is consistent with a model in which enhancers act to establish and
      maintain an active domain without directly affecting the transcriptional rate.

PMID- 9032287
TI  - Antiapoptotic signalling by the insulin-like growth factor I receptor,
      phosphatidylinositol 3-kinase, and Akt.
AB  - We have found that insulin-like growth factor I (IGF-I) can protect fibroblasts
      from apoptosis induced by UV-B light. Antiapoptotic signalling by the IGF-I
      receptor depended on receptor kinase activity, as cells overexpressing kinase
      defective receptor mutants could not be protected by IGF-I. Overexpression of a
      kinase-defective receptor which contained a mutation in the ATP binding loop
      functioned as a dominant negative and sensitized cells to apoptosis. The
      antiapoptotic capacity of the IGF-I receptor was not shared by other growth
      factors tested, including epidermal growth factor (EGF) and thrombin, although
      the cells expressed functional receptors for all the agonists. However, EGF was
      antiapoptotic for cells overexpressing the EGF receptor, and expression of
      activated pp60v-src also was protective. There was no correlation between
      protection from apoptosis and activation of mitogen-activated protein kinase,
      p38/HOG1, or p70S6 kinase. On the other hand, protection by any of the tyrosine
      kinases against UV-induced apoptosis was blocked by wortmannin, implying a role
      for phosphatidylinositol 3-kinase (PI3 kinase). To test this, we transiently
      expressed constitutively active or kinase-dead PI3 kinase and found that
      overexpression of activated phosphatidylinositol 3-kinase (PI3 kinase) was
      sufficient to provide protection against apoptosis. Because Akt/PKB is believed
      to be a downstream effector for PI3 kinase, we also examined the role of this
      serine/threonine protein kinase in antiapoptotic signalling. We found that
      membrane-targeted Akt was sufficient to protect against apoptosis but that kinase
      dead Akt was not. We conclude that the endogenous IGF-I receptor has a specific
      antiapoptotic signalling capacity, that overexpression of other tyrosine kinases
      can allow them also to be antiapoptotic, and that activation of PI3 kinase and
      Akt is sufficient for antiapoptotic signalling.

PMID- 9032289
TI  - DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as
      a putative modulator of gamma interferon-induced programmed cell death.
AB  - A functional approach to gene cloning was applied to HeLa cells in an attempt to
      isolate cDNA fragments which convey resistance to gamma interferon (IFN-gamma)
      induced programmed cell death. One of the rescued cDNAs, described in this work,
      was a fragment of a novel gene, named DAP-5. Analysis of a DAP-5 full-length cDNA
      clone revealed that it codes for a 97-kDa protein that is highly homologous to
      eukaryotic translation initiation factor 4G (eIF4G, also known as p220).
      According to its deduced amino acid sequence, this novel protein lacks the N
      terminal region of eIF4G responsible for association with the cap binding protein
      eIF4E. The N-terminal part of DAP-5 has 39% identity and 63% similarity to the
      central region of mammalian p220. Its C-terminal part is less homologous to the
      corresponding region of p220, suggesting that it may possess unique functional
      properties. The rescued DAP-5 cDNA fragment which conveyed resistance to IFN
      gamma-induced cell death was expressed from the vector in the sense orientation.
      Intriguingly, it comprised part of the coding region which corresponds to the
      less conserved C-terminal part of DAP-5 and directed the synthesis of a 28-kDa
      miniprotein. The miniprotein exerted a dual effect on HeLa cells. Low levels of
      expression protected the cells from IFN-gamma-induced programmed cell death,
      while high levels of expression were not compatible with continuous cell growth.
      The relevance of DAP-5 protein to possible changes in a cell's translational
      machinery during programmed cell death and growth arrest is discussed.

PMID- 9032291
TI  - Erythroid-cell-specific properties of transcription factor GATA-1 revealed by
      phenotypic rescue of a gene-targeted cell line.
AB  - The zinc finger transcription factor GATA-1 is essential for erythropoiesis. In
      its absence, committed erythroid precursors arrest at the proerythroblast stage
      of development and undergo apoptosis. To study the function of GATA-1 in an
      erythroid cell environment, we generated an erythroid cell line from in vitro
      differentiated GATA-1- murine embryonic stem (ES) cells. These cells, termed G1E
      for GATA-1- erythroid, proliferate as immature erythroblasts yet complete
      differentiation upon restoration of GATA-1 function. We used rescue of terminal
      erythroid maturation in G1E cells as a stringent cellular assay system in which
      to evaluate the functional relevance of domains of GATA-1 previously
      characterized in nonhematopoietic cells. At least two major differences were
      established between domains required in G1E cells and those required in
      nonhematopoietic cells. First, an obligatory transactivation domain defined in
      conventional nonhematopoietic cell transfection assays is dispensable for
      terminal erythroid maturation. Second, the amino (N) zinc finger, which is
      nonessential for binding to the vast majority of GATA DNA motifs, is strictly
      required for GATA-1-mediated erythroid differentiation. Our data lead us to
      propose a model in which a nuclear cofactor(s) interacting with the N-finger
      facilitates transcriptional action by GATA-1 in erythroid cells. More generally,
      our experimental approach highlights critical differences in the action of cell
      specific transcription proteins in different cellular environments and the power
      of cell lines derived from genetically modified ES cells to elucidate gene
      function.

PMID- 9032290
TI  - Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating
      epithelial and mesenchymal cells of embryonic and adult tissues.
AB  - The hepatocyte nuclear factor 3alpha (HNF-3alpha) and 3beta proteins have
      homology in the winged helix/fork head DNA binding domain and regulate cell
      specific transcription in hepatocytes and in respiratory and intestinal
      epithelia. In this study, we describe two novel isoforms of the winged helix
      transcription factor family, HNF-3/fork head homolog 11A (HFH-11A) and HFH-11B,
      isolated from the human colon carcinoma HT-29 cell line. We show that these
      isoforms arise via differential splicing and are expressed in a number of
      epithelial cell lines derived from tumors (HT-29, Caco-2, HepG2, HeLa, A549, and
      H441). We demonstrate that differentiation of Caco-2 cells toward the enterocyte
      lineage results in decreased HFH-11 expression and reciprocal increases in HNF
      3alpha and HNF-3beta mRNA levels. In situ hybridization of 16 day postcoitus
      mouse embryos demonstrates that HFH-11 expression is found in the mesenchymal and
      epithelial cells of the liver, lung, intestine, renal cortex, and urinary tract.
      Although HFH-11 exhibits a wide cellular expression pattern in the embryo, its
      adult expression pattern is restricted to epithelial cells of Lieberkuhn's crypts
      of the intestine, the spermatocytes and spermatids of the testis, and the thymus
      and colon. HFH-11 expression is absent in adult hepatocytes, but its expression
      is reactivated in proliferating hepatocytes at 4, 24, and 48 h after partial
      hepatectomy. Consistent with these findings, we demonstrate that HFH-11 mRNA
      levels are stimulated by intratracheal administration of keratinocyte growth
      factor in adult lung and its expression in an adult endothelial cell line is
      reactivated in response to oxidative stress. These experiments show that the HFH
      11 transcription factor is expressed in embryonic mesenchymal and epithelial
      cells and its expression is reactivated in these adult cell types by
      proliferative signals or oxidative stress.

PMID- 9032293
TI  - Concerted evolution at a multicopy locus in the protozoan parasite Theileria
      parva: extreme divergence of potential protein-coding sequences.
AB  - Concerted evolution of multicopy gene families in vertebrates is recognized as an
      important force in the generation of biological novelty but has not been
      documented for the multicopy genes of protozoa. A multicopy locus, Tpr, which
      consists of tandemly arrayed open reading frames (ORFs) containing several
      repeated elements has been described for Theileria parva. Herein we show that
      probes derived from the 5'/N-terminal ends of ORFs in the genomic DNAs of T.
      parva Uganda (1,108 codons) and Boleni (699 codons) hybridized with multicopy
      sequences in homologous DNA but did not detect similar sequences in the DNA of 14
      heterologous T. parva stocks and clones. The probe sequences were, however,
      protein coding according to predictive algorithms and codon usage. The 3'/C
      terminal ends of the Uganda and Boleni ORFs exhibited 75% similarity and
      identity, respectively, to the previously identified Tpr1 and Tpr2 repetitive
      elements of T. parva Muguga. Tpr1-homologous sequences were detected in two
      additional species of Theileria. Eight different Tpr1-homologous transcripts were
      present in piroplasm mRNA from a single T. parva Muguga-infected animal. The Tpr1
      and Tpr2 amino acid sequences contained six predicted membrane-associated
      segments. The ratio of synonymous to nonsynonymous substitutions indicates that
      Tpr1 evolves like protein-encoding DNA. The previously determined nucleotide
      sequence of the gene encoding the p67 antigen is completely identical in T. parva
      Muguga, Boleni, and Uganda, including the third base in codons. The data suggest
      that concerted evolution can lead to the radical divergence of coding sequences
      and that this can be a mechanism for the generation of novel genes.

PMID- 9032292
TI  - Repression of gonadotropin-releasing hormone promoter activity by the POU
      homeodomain transcription factor SCIP/Oct-6/Tst-1: a regulatory mechanism of
      phenotype expression?
AB  - POU domain transcription factors are required for neuropeptide expression in
      selected subsets of hypothalamic neuroendocrine neurons. We now report that
      expression of the gonadotropin-releasing hormone (GnRH) gene, which controls
      sexual development, is regulated by the POU protein SCIP/Oct-6/Tst-1. Reverse
      transcriptase PCR cloning and RNase protection assays demonstrated the presence
      of SCIP/Oct-6/Tst-1 mRNA in the GnRH-producing neuronal cell line GT1-7. The
      physiological relevance of this regulatory activity was suggested by the
      detection of SCIP/Oct-6/Tst-1 mRNA in a subset of GnRH neurons in the
      hypothalamus of prepubertal female rats. Coexpression of SCIP/Oct-6/Tst-1 in
      neuronal cells inhibited rat GnRH (rGnRH) promoter activity via three regions of
      the proximal rGnRH promoter containing SCIP/Oct-6/Tst-1 binding sites. DNase I
      footprinting, gel shift assays, and DNA and protein mutagenesis studies indicated
      that both direct DNA binding and protein-protein interactions are required for
      SCIP/Oct-6/Tst-1 modulation of GnRH gene expression. Activation of SCIP/Oct-6/Tst
      1 expression in terminally differentiated GnRH neurons may be a factor
      determining the ratio of phenotypically "inactive" versus "active" GnRH neurons
      during postnatal life.

PMID- 9032294
TI  - The Sex-lethal early splicing pattern uses a default mechanism dependent on the
      alternative 5' splice sites.
AB  - The Sex-lethal (Sxl) early transcripts have a unique 5' exon and a splicing
      pattern that differs from that of the late transcripts. While the late
      transcripts are regulated sex specifically by control of exon 3 inclusion, the
      early transcripts are not. While the late transcripts include exon 3 by default,
      the early transcripts skip exon 3. Splicing patterns of a reporter gene that
      mimics the early transcript, and its variants, were analyzed in Drosophila
      transformants and tissue culture cells. The results demonstrate that the early,
      in contrast to the late, splicing pattern is not regulated by stage-specific or
      sex-specific trans-acting factors, and so the pattern appears to arise from some
      type of intrinsic splice site preference or compatibility. Inclusion or exclusion
      of exon 3 is determined by the identity of the upstream 5' splice site region as
      late or early. The important region of the early exon lies within 233 nucleotides
      of the immediately adjacent intron.

PMID- 9032295
TI  - Activin and inhibin have antagonistic effects on ligand-dependent
      heteromerization of the type I and type II activin receptors and human erythroid
      differentiation.
AB  - Activins and inhibins belong to the transforming growth factor beta (TGF-beta)
      like superfamily and exert their effects on a broad range of cellular targets by
      modulating cell differentiation and proliferation. Members of this family
      interact with two structurally related classes of receptors (type I and type II),
      both containing a serine/threonine kinase domain. When expressed alone, the type
      II but not the type I activin receptor can bind activin. However, the presence of
      a type I receptor is required for signaling. For TGF-beta1, ligand binding to the
      type II receptor results in the recruitment and transphosphorylation of the type
      I receptor. Transient overexpression of the two types of activin receptor results
      in ligand-independent receptor heteromerization and activation. Nevertheless,
      activin addition to the transfected cells increased complex formation between the
      two receptors, suggesting a mechanism of action similar to that observed for the
      TGF-beta receptor. In the present study, we generated a stable cell line,
      overexpressing the two types of activin receptor upon induction, in the human
      erythroleukemia cell line K562. We demonstrate here that activin specifically
      induces heteromer formation between the type I and type II receptors in a time
      dependent manner. Using this stable line, we analyzed the effects of activin and
      inhibin on human erythroid differentiation. Our results indicate that activin
      signal transduction mediated through its type I and type II receptors results in
      an increase in the hemoglobin content of the cells and limits their
      proliferation. Finally, using cell lines that can be induced to overexpress
      ActRII and ActRIB or ActRIB only, we show that the inhibin antagonistic effects
      on activin-induced biological responses are mediated through a competition for
      the type II activin receptor but also require the presence of an inhibin-specific
      binding component.

PMID- 9032296
TI  - Separation of PP2A core enzyme and holoenzyme with monoclonal antibodies against
      the regulatory A subunit: abundant expression of both forms in cells.
AB  - Protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit, C,
      and two regulatory subunits, A and B. The A subunit is rod shaped and consists of
      15 nonidentical repeats. According to our previous model, the B subunit binds to
      repeats 1 through 10 and the C subunit binds to repeats 11 through 15 of the A
      subunit. Another form of PP2A, core enzyme, is composed only of subunits A and C.
      It is generally believed that core enzyme does not exist in cells but is an
      artifact of enzyme purification. To study the structure and relative abundance of
      different forms of PP2A, we generated monoclonal antibodies against the native A
      subunit. Two antibodies, 5H4 and 1A12, recognized epitopes in repeat 1 near the N
      terminus and immunoprecipitated free A subunit and core enzyme but not
      holoenzyme. Another antibody, 6G3, recognized an epitope in repeat 15 at the C
      terminus and precipitated only the free A subunit. Monoclonal antibodies against
      a peptide corresponding to the N-terminal 11 amino acids of the A alpha subunit
      (designated 6F9) precipitated free A subunit, core enzyme, and holoenzyme. 6F9,
      but not 5H4, recognized holoenzymes containing either B, B', or B" subunits.
      These results demonstrate that B subunits from three unrelated gene families all
      bind to repeat 1 of the A subunit, and the results confirm and extend our model
      of the holoenzyme. By sequential immunoprecipitations with 5H4 or 1A12 followed
      by 6F9, core enzyme and holoenzyme in cytoplasmic extracts from 10T1/2 cells were
      completely separated and they exhibited the expected specificities towards
      phosphorylase a and retinoblastoma peptide as substrates. Quantitative analysis
      showed that under conditions which minimized proteolysis and dissociation of
      holoenzyme, core enzyme represented at least one-third of the total PP2A. We
      conclude that core enzyme is an abundant form in cells rather than an artifact of
      isolation. The biological implications of this finding are discussed.

PMID- 9032297
TI  - Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex:
      involvement of the Grb2, p130cas, and Nck adaptor proteins.
AB  - The focal adhesion kinase (FAK), a protein-tyrosine kinase (PTK), associates with
      integrin receptors and is activated by cell binding to extracellular matrix
      proteins, such as fibronectin (FN). FAK autophosphorylation at Tyr-397 promotes
      Src homology 2 (SH2) domain binding of Src family PTKs, and c-Src phosphorylation
      of FAK at Tyr-925 creates an SH2 binding site for the Grb2 SH2-SH3 adaptor
      protein. FN-stimulated Grb2 binding to FAK may facilitate intracellular signaling
      to targets such as ERK2-mitogen-activated protein kinase. We examined FN
      stimulated signaling to ERK2 and found that ERK2 activation was reduced 10-fold
      in Src- fibroblasts, compared to that of Src- fibroblasts stably reexpressing
      wild-type c-Src. FN-stimulated FAK phosphotyrosine (P.Tyr) and Grb2 binding to
      FAK were reduced, whereas the tyrosine phosphorylation of another signaling
      protein, p130cas, was not detected in the Src- cells. Stable expression of
      residues 1 to 298 of Src (Src 1-298, which encompass the SH3 and SH2 domains of c
      Src) in the Src- cells blocked Grb2 binding to FAK; but surprisingly, Src 1-298
      expression also resulted in elevated p130cas P.Tyr levels and a two- to threefold
      increase in FN-stimulated ERK2 activity compared to levels in Src- cells. Src 1
      298 bound to both FAK and p130cas and promoted FAK association with p130cas in
      vivo. FAK was observed to phosphorylate p130cas in vitro and could thus
      phosphorylate p130cas upon FN stimulation of the Src 1-298-expressing cells. FAK
      induced phosphorylation of p130cas in the Src 1-298 cells promoted the SH2 domain
      dependent binding of the Nck adaptor protein to p130cas, which may facilitate
      signaling to ERK2. These results show that there are additional FN-stimulated
      pathways to ERK2 that do not involve Grb2 binding to FAK.

PMID- 9032298
TI  - Ultrabithorax and Antennapedia 5' untranslated regions promote developmentally
      regulated internal translation initiation.
AB  - The 5' untranslated regions (UTRs) of the Drosophila Ubx and Antp genes were
      tested for their ability to promote cap-independent translation initiation. The
      Ubx and the Antp 5' UTR were inserted between the CAT and lacZ coding sequences
      in a dicistronic gene and tested for IRES activity in transgenic Drosophila.
      Northern analysis of the mRNAs showed the presence of the predicted full-length
      dicistronic mRNAs. High CAT activity was expressed from the first cistron from
      all of the dicistronic constructs introduced into the fly genome. The dicistronic
      transgenic strains bearing the Ubx and Antp IRES elements expressed significant
      levels of beta-galactosidase (betaGAL) from the second cistron whereas little or
      no betaGAL was expressed in the controls lacking the IRESs. In situ analysis of
      betaGAL expression in the transgenic strains indicates that expression of the
      second cistron is spatially and temporally regulated. Although the developmental
      patterns of expression directed by the Antp and Ubx IRESs overlap, they exhibit
      several differences indicating that these IRESs are not functionally equivalent.

PMID- 9032299
TI  - Constitutive expression in gal7 mutants of Kluyveromyces lactis is due to
      internal production of galactose as an inducer of the Gal/Lac regulon.
AB  - The induction process of the galactose regulon has been intensively studied, but
      until now the nature of the inducer has remained unknown. We have analyzed a
      delta gal7 mutant of the yeast Kluyveromyces lactis, which lacks the
      galactotransferase activity and is able to express the genes of the Gal/Lac
      regulon also in the absence of galactose. We found that this expression is
      semiconstitutive and undergoes a strong induction during the stationary phase.
      The gal1-209 mutant, which has a reduced kinase activity but retains its positive
      regulatory function, also shows a constitutive expression of beta-galactosidase,
      suggesting that galactose is the inducer. A gal10 deletion in delta gal7 or gal1
      209 mutants reduces the expression to under wild-type levels. The presence of the
      inducer could be demonstrated in both delta gal7 crude extracts and culture
      medium by means of a bioassay using the induction in gal1-209 cells. A mutation
      in the transporter gene LAC12 decreases the level of induction in gal7 cells,
      indicating that galactose is partly released into the medium and then
      retransported into the cells. Nuclear magnetic resonance analysis of crude
      extracts from delta gal7 cells revealed the presence of 50 microM galactose. We
      conclude that galactose is the inducer of the Gal/Lac regulon and is produced via
      UDP-galactose through a yet-unknown pathway.

PMID- 9032300
TI  - Serum response factor and protein-mediated DNA bending contribute to
      transcription of the dystrophin muscle-specific promoter.
AB  - The minimal muscle-specific dystrophin promoter contains the consensus sequence
      CC(A/T)6GG, or the CArG element, which can be found in serum-inducible or muscle
      specific promoters. The serum response factor (SRF), which mediates the
      transcriptional activation of the c-fos gene in response to serum stimulation,
      can bind to different CArG box elements, suggesting that it could be involved in
      muscle-constitutive transcription. Here we show that SRF binds to the dystrophin
      promoter and regulates its muscle-specific transcription. In transient
      transfections, an altered-binding-specificity SRF mutant restores the muscle
      constitutive transcription of a dystrophin promoter with a mutation in its CArG
      box element. The muscle-constitutive transcription of the dystrophin promoter
      also requires the sequence GAAACC immediately downstream of the CArG box. This
      sequence is recognized by a novel DNA bending factor which was named dystrophin
      promoter-bending factor (DPBF). Mutations of the CArG flanking sequence abolish
      both DPBF binding and the promoter activity in muscle cells. Its replacement with
      a p62/ternary complex factor binding site changes the promoter specificity from
      muscle constitutive to serum responsive. These results show that, on the
      dystrophin promoter, the transcriptional activation induced by SRF requires the
      DNA bending induced by DPBF. The bending, next to the CArG box, could promote
      interactions between SRF and other proteins in the transcriptional complex.

PMID- 9032301
TI  - Regulation of the cfos serum response element by C/EBPbeta.
AB  - Serum response element binding protein (SRE BP) is a novel binding factor present
      in nuclear extracts of avian and NIH 3T3 fibroblasts which specifically binds to
      the cfos SRE within a region overlapping and immediately 3' to the CArG box. Site
      directed mutagenesis combined with transfection experiments in NIH 3T3 cells
      showed that binding of both serum response factor (SRF) and SRE BP is necessary
      for maximal serum induction of the SRE. In this study, we have combined size
      fractionation of the SRE BP DNA binding activity with C/EBPbeta antibodies to
      demonstrate that homodimers and heterodimers of p35C/EBPbeta (a transactivator)
      and p20C/EBPbeta (a repressor) contribute to the SRE BP complex in NIH 3T3 cells.
      Transactivation of the SRE by p35C/EBPbeta is dependent on SRF binding but not
      ternary complex factor (TCF) formation. Both p35C/EBPbeta and p20C/EBPbeta bind
      to SRF in vitro via a carboxy-terminal domain that probably does not include the
      leucine zipper. Moreover, SRE mutants which retain responsiveness to the TCF
      independent signaling pathway bind SRE BP in vitro with affinities that are
      nearly identical to that of the wild-type SRE, whereas mutant SRE.M, which is not
      responsive to the TCF-independent pathway, has a nearly 10-fold lower affinity
      for SRE BP. We propose that C/EBPbeta may play a role in conjunction with SRF in
      the TCF-independent signaling pathway for SRE activation.

PMID- 9032302
TI  - Regulation of apoptosis by viral gene products.

PMID- 9032303
TI  - The cellular transcription factor SP1 and an unknown cellular protein are
      required to mediate Rep protein activation of the adeno-associated virus p19
      promoter.
AB  - Control of adeno-associated virus (AAV) transcription from the three AAV
      promoters (p5, p19, and p40) requires the adenovirus E1a protein and the AAV
      nonstructural (Rep) proteins. The Rep proteins have been shown to repress the AAV
      p5 promoter yet facilitate activation of the p19 and p40 promoters during a
      productive infection. To elucidate the mechanism of promoter regulation by the
      AAV Rep proteins, the cellular factors involved in mediating Rep activation of
      the p19 promoter were characterized. A series of protein-DNA binding experiments
      using extracts derived from uninfected HeLa cells was performed to identify
      cellular factors that bind to the p19 promoter. Electrophoretic mobility shift
      assays, DNase I protection analyses, and UV cross-linking experiments
      demonstrated specific interactions with the cellular factor SP1 (or an SP1-like
      protein) at positions -50 and -130 relative to the start of p19 transcription.
      Additionally, an unknown cellular protein (cellular AAV activating protein
      [cAAP]) with an approximate molecular mass of 34 kDa was found to interact with a
      CArG-like element at position -140. Mutational analysis of the p19 promoter
      suggested that the SP1 site at -50 and the cAAP site at -140 were necessary to
      mediate Rep activation of p19. Antibody precipitation experiments demonstrated
      that Rep-SP1 protein complexes can exist in vivo. Although Rep was demonstrated
      to interact with p19 DNA directly, the affinity of Rep binding was much lower
      than that seen for the Rep binding elements within the terminal repeat and the p5
      promoter. Furthermore, the interaction of purified Rep68 with the p19 promoter in
      vitro was negligible unless purified SP1 was also added to the reaction. Thus,
      the ability of Rep to transactivate the p19 promoter is likely to involve SP1-Rep
      protein contacts that facilitate Rep interaction with p19 DNA.

PMID- 9032304
TI  - Identification of a promoter-specific transactivation domain in the herpes
      simplex virus regulatory protein ICP4.
AB  - ICP4 is expressed during the immediate-early phase of infection by herpes simplex
      virus (HSV) and activates transcription of viral genes during subsequent phases
      of productive infection. Several members of the alpha-herpesvirus family encode
      regulatory proteins that have extensive homology with ICP4 and exhibit a
      transactivation domain (TAD) at the N terminus. The portions of ICP4 required for
      nuclear localization, DNA binding, and dimerization have been defined, but a
      domain that is specifically required for transactivation has not been identified.
      We have defined a promoter-specific ICP4 TAD by analysis of the activity of GAL4
      ICP4 fusion proteins cotransfected into HeLa cells with a luciferase reporter
      gene linked to a promoter with five GAL4 binding sites. The transactivation
      activity of GAL4-ICP4 hybrids is located entirely within the first 139 residues
      of ICP4 and is significantly less potent than the activity of GAL4-TAD hybrids
      derived from ICP4 homologs. ICP4 residues 97 to 109 are a critical component of
      this N-terminal TAD. Transient transfection assays performed with nonfusion forms
      of ICP4 and luciferase genes linked to the HSV glycoprotein D (gD) or thymidine
      kinase (tk) promoter revealed that ICP4 residues 97 to 109 are required for
      induction of the gD promoter but are not required for induction of the tk
      promoter. Comparative experiments with ICP4 homologs revealed that the
      pseudorabies virus TAD is a potent activator of the gD promoter and a weak
      activator of the tk promoter. Complementation assays revealed that loss of ICP4
      residues 97 to 109 reduced the yield of virus from infected cells nearly 500-fold
      compared to wild-type ICP4. We conclude that ICP4 residues 97 to 109 are a core
      component of a promoter-specific transactivation domain that is required for
      efficient replication of herpes simplex virus.

PMID- 9032305
TI  - Dominant-negative inhibitors of EBNA-1 of Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is required in trans to
      support replication of the EBV genome once per cell cycle via the latent origin
      of replication, oriP. EBNA-1 can also activate transcription on binding to the
      family of repeats of oriP to enhance some heterologous as well as native EBV
      promoters. We have made and screened derivatives of EBNA-1 for the ability to act
      as inhibitors of wild-type EBNA-1. These derivatives lack the linking or the
      retention functions of EBNA-1 and were analyzed for the residual ability to
      activate transcription and replication. We have identified derivatives of EBNA-1
      that can inhibit up to 98% of wild-type EBNA-1's activities. We have also
      identified one derivative of EBNA-1 with only two of EBNA-1's three linking
      domains which can support transcription and replication inefficiently.

PMID- 9032306
TI  - Recombinant adeno-associated virus mediates a high level of gene transfer but
      less efficient integration in the K562 human hematopoietic cell line.
AB  - We tested the ability of a recombinant adeno-associated virus (rAAV) vector to
      express and integrate exogenous DNA into human hematopoietic cells in the absence
      of selection. We developed an rAAV vector, AAV-tNGFR, carrying a truncated rat
      nerve growth factor receptor (tNGFR) cDNA as a cell surface reporter under the
      control of the Moloney murine leukemia virus (MoMuLV) long terminal repeat. An
      analogous MoMuLV-based retroviral vector (L-tNGFR) was used in parallel, and gene
      transfer and expression in human hematopoietic cells were assessed by flow
      cytometry and DNA analyses. Following gene transfer into K562 cells with AAV
      tNGFR at a multiplicity of infection (MOI) of 13 infectious units (IU), 26 to 38%
      of cells expressed tNGFR on the surface early after transduction, but the
      proportion of tNGFR expressing cells steadily declined to 3.0 to 3.5% over 1
      month of culture. At an MOI of 130 IU, nearly all cells expressed tNGFR
      immediately posttransduction, but the proportion of cells expressing tNGFR
      declined to 62% over 2 months of culture. The decline in the proportion of AAV
      tNGFR-expressing cells was associated with ongoing losses of vector genomes. In
      contrast, K562 cells transduced with the retroviral vector L-tNGFR expressed
      tNGFR in a constant fraction. Integration analyses on clones showed that
      integration occurred at different sites. Integration frequencies were estimated
      at about 49% at an MOI of 130 and 2% at an MOI of 1.3. Transduction of primary
      human CD34+ progenitor cells by AAV-tNGFR was less efficient than with K562 cells
      and showed a declining percentage of cells expressing tNGFR over 2 weeks of
      culture. Thus, purified rAAV caused very high gene transfer and expression in
      human hematopoietic cells early after transduction, which steadily declined
      during cell passage in the absence of selection. Although the efficiency of
      integration was low, overall integration was markedly improved at a high MOI.
      While prolonged episomal persistence may be adequate for gene therapy of
      nondividing cells, a very high MOI or improvements in basic aspects of AAV-based
      vectors may be necessary to improve integration frequency in the rapidly dividing
      hematopoietic cell population.

PMID- 9032307
TI  - Herpes simplex virus immediate-early proteins ICP0 and ICP4 activate the
      endogenous human alpha-globin gene in nonerythroid cells.
AB  - Globin genes are normally expressed only in erythroid cell lineages. However, we
      found that the endogenous alpha-globin gene is activated following infection of
      human fibroblasts and HeLa cells with herpes simplex virus (HSV), leading to
      accumulation of correctly initiated transcripts driven by the alpha-globin
      promoter. The alpha1- and alpha2-globin genes were both induced, but expression
      of beta- or zeta-globin genes could not be detected. Experiments using HSV
      mutants showed that null mutations in the genes encoding the viral immediate
      early proteins ICP4 and ICP22 reduced induction approximately 10-fold, while loss
      of ICP0 function had a smaller inhibitory effect. Transient transfection
      experiments showed that ICP0 and ICP4 are each sufficient to trigger detectable
      expression of the endogenous gene, while ICP22 had no detectable effect in this
      assay. ICP4 also strongly enhanced expression of transfected copies of the alpha2
      globin gene. In contrast, the adenovirus E1a protein did not activate the
      endogenous gene and inhibited expression of the plasmid-borne alpha2-globin gene.
      Previous studies have led to the hypothesis that chromosomal alpha-globin genes
      are subject to chromatin-dependent repression mechanism that prevents expression
      in nonerythroid cells. Our data suggest that HSV ICP0 and ICP4 either break or
      bypass this cellular gene silencing mechanism.

PMID- 9032308
TI  - Role of the intergenic dinucleotide in vesicular stomatitis virus RNA
      transcription.
AB  - To investigate the role played by the intergenic dinucleotide sequence of the
      conserved vesicular stomatitis virus (VSV) gene junction in modulation of
      polymerase activity, we analyzed the RNA synthesis activities of bicistrionic
      genomic analogs that contained either the authentic N/P gene junction or gene
      junctions that had been altered to contain either the 16 possible dinucleotide
      combinations, single nucleotide intergenic sequences, or no intergenic sequence
      at all. Quantitative measurements of the amounts of upstream, downstream, and
      readthrough mRNAs that were transcribed by these mutant templates showed that the
      behavior of the viral polymerase was profoundly affected by the nucleotide
      sequence that it encountered as it traversed the gene junction, although the
      polymerase was able to accommodate a remarkable degree of sequence variation
      without altogether losing the ability to terminate and reinitiate transcription.
      Alteration or removal of the intergenic sequence such that the U tract
      responsible for synthesis of the upstream mRNA poly(A) tail was effectively
      positioned adjacent to the consensus downstream gene start signal resulted in
      almost complete abrogation of downstream mRNA synthesis, thus defining the
      intergenic sequence as an essential sequence element of the gene junction. Many
      genome analogs with altered intergenic sequences directed abundant synthesis of a
      readthrough transcript without correspondingly high levels of downstream mRNA, an
      observation inconsistent with the shunting model of VSV transcription, which
      suggests that polymerase molecules are prepositioned at gene junctions, awaiting
      a push from upstream. Instead, the findings of this study support a model of
      sequential transcription in which initiation of downstream mRNA can occur only
      following termination of the preceding transcript.

PMID- 9032309
TI  - Antiviral immune responses in CTLA4 transgenic mice.
AB  - The role of B7 binding CD28 in the regulation of T- and B-cell responses against
      viral antigens was assessed in transgenic mice expressing soluble CTLA4-Hgamma1
      (CTLA4-Ig tg mice) that blocks B7-CD28 interactions. The results indicate that
      transgenic soluble CTLA4 does not significantly alter cytotoxic T-cell responses
      against replicating lymphocytic choriomeningitis virus (LCMV) or vaccinia virus
      but drastically impairs the induction of cytotoxic T-cell responses against
      abortively replicating vesicular stomatitis virus (VSV). While the T-independent
      neutralizing immunoglobulin M (IgM) responses were within normal ranges, the
      switch to IgG was reduced 4- to 16-fold after immunization with abortively
      replicating VSV and more than 30-fold after immunization with an inert VSV
      glycoprotein antigen in transgenic mice. IgG antibody responses to LCMV, as
      detected by enzyme-linked immunosorbent assay and by neutralizing action, were
      reduced about 3- to 20-fold and more than 50-fold, respectively. These results
      suggest that responses in CTLA4-Ig tg mice are mounted according to their
      independence of T help. While immune responses to nonreplicating or poorly
      replicating antigens are in general most dependent on T help and B7-CD28
      interactions, they are most impaired in CTLA4-Ig tg mice. The results of the
      present experiments also indicate that highly replicating viruses, because of
      greater quantities of available antigens and by inducing as-yet-undefined factors
      and/or cell surface changes, are capable of compensating for the decrease in T
      help caused by the blocking effects of soluble CTLA4.

PMID- 9032310
TI  - Control of immunodeficiency and lymphoproliferation in mouse AIDS: studies of
      mice deficient in CD8+ T cells or perforin.
AB  - CD8+ T cells were previously shown to be important in preventing
      lymphoproliferation and immunodeficiency following infection of murine AIDS
      (MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia viruses. To
      further evaluate the mechanisms contributing to MAIDS resistance, we studied mice
      lacking CD8+ T cells or deficient in perforin due to knockout of the beta2
      microglobulin (beta2M) or perforin gene, respectively. In contrast to wild-type,
      MAIDS-resistant controls, B10.A mice homozygous for the beta2M mutation and
      B10.D2 mice homozygous for the perforin mutation were diagnosed as having MAIDS
      by 5 to 8 weeks after infection by the criteria of lymphoproliferation, impaired
      proliferative responses to mitogens, and changes in cell populations as judged by
      histopathology and flow cytometry. Unexpectedly, there was no progression of
      lymphoproliferation through 24 weeks, even though immune functions were severely
      compromised. Expression of the defective virus responsible for MAIDS was enhanced
      in spleens of the knockouts in comparison with wild-type mice. These results
      demonstrate that perforin-dependent functions of CD8+ T cells contribute to MAIDS
      resistance but that other, non-CD8-dependent mechanisms are of equal or greater
      importance.

PMID- 9032311
TI  - Proteolytic processing of the coronavirus infectious bronchitis virus 1a
      polyprotein: identification of a 10-kilodalton polypeptide and determination of
      its cleavage sites.
AB  - Proteolytic processing of the polyprotein encoded by mRNA 1 is an essential step
      in coronavirus RNA replication and gene expression. We have previously reported
      that an open reading frame (ORF) 1a-specific proteinase of the picornavirus 3C
      proteinase group is involved in processing of the coronavirus infectious
      bronchitis virus (IBV) 1a/1b polyprotein, leading to the formation of a mature
      viral protein of 100 kDa. We report here the identification of a novel 10-kDa
      polypeptide and the involvement of the 3C-like proteinase in processing of the
      ORF 1a polyprotein to produce the 10-kDa protein species. By using a region
      specific antiserum, V47, raised against a bacterial-viral fusion protein
      containing IBV sequence encoded between nucleotides 11488 and 12600, the 10-kDa
      polypeptide was detected in lysates from both IBV-infected and plasmid DNA
      transfected Vero cells. Coexpression, deletion, and mutagenesis studies showed
      that this novel polypeptide was encoded by ORF 1a from nucleotide 11545 to 11878
      and was cleaved from the 1a polyprotein by the 3C-like proteinase domain.
      Evidence presented suggested that a previously predicted Q-S (Q3783 S3784)
      dipeptide bond encoded by ORF 1a between nucleotides 11875 and 11880 was
      responsible for the release of the C terminus of the 10-kDa polypeptide and that
      a novel Q-N (Q3672 N3673) dipeptide bond encoded between nucleotides 11542 and
      11547 was responsible for the release of the N terminus of the 10-kDa
      polypeptide.

PMID- 9032312
TI  - Characterization of early stages in vaccinia virus membrane biogenesis:
      implications of the 21-kilodalton protein and a newly identified 15-kilodalton
      envelope protein.
AB  - Vaccinia virus (VV) membrane biogenesis is a poorly understood process. It has
      been proposed that cellular membranes derived from the endoplasmic reticulum
      Golgi intermediate compartment (ERGIC) are incorporated in the early stages of
      virion assembly. We have recently shown that the VV 21-kDa (A17L gene) envelope
      protein is essential for the formation of viral membranes. In the present work,
      we identify a 15-kDa VV membrane protein encoded by the A14L gene. This protein
      is phosphorylated and myristylated during infection and is incorporated into the
      virion envelope. Both the 21- and 15-kDa proteins are found associated with
      cellular tubulovesicular elements related to the ERGIC, suggesting that these
      proteins are transported in these membranes to the nascent viral factories. When
      synthesis of the 21-kDa protein is repressed, organized membranes are not formed
      but numerous ERGIC-derived tubulovesicular structures containing the 15-kDa
      protein accumulate in the boundaries of the precursors of the viral factories.
      These data suggest that the 21-kDa protein is involved in organizing the
      recruited viral membranes, while the 15-kDa protein appears to be one of the
      viral elements participating in the membrane recruitment process from the ERGIC,
      to initiate virus formation.

PMID- 9032313
TI  - Mutations in type 3 reovirus that determine binding to sialic acid are contained
      in the fibrous tail domain of viral attachment protein sigma1.
AB  - The reovirus attachment protein, sigma1, determines numerous aspects of reovirus
      induced disease, including viral virulence, pathways of spread, and tropism for
      certain types of cells in the central nervous system. The sigma1 protein projects
      from the virion surface and consists of two distinct morphologic domains, a
      virion-distal globular domain known as the head and an elongated fibrous domain,
      termed the tail, which is anchored into the virion capsid. To better understand
      structure-function relationships of sigma1 protein, we conducted experiments to
      identify sequences in sigma1 important for viral binding to sialic acid, a
      component of the receptor for type 3 reovirus. Three serotype 3 reovirus strains
      incapable of binding sialylated receptors were adapted to growth in murine
      erythroleukemia (MEL) cells, in which sialic acid is essential for reovirus
      infectivity. MEL-adapted (MA) mutant viruses isolated by serial passage in MEL
      cells acquired the capacity to bind sialic acid-containing receptors and
      demonstrated a dependence on sialic acid for infection of MEL cells. Analysis of
      reassortant viruses isolated from crosses of an MA mutant virus and a reovirus
      strain that does not bind sialic acid indicated that the sigma1 protein is solely
      responsible for efficient growth of MA mutant viruses in MEL cells. The deduced
      sigma1 amino acid sequences of the MA mutant viruses revealed that each strain
      contains a substitution within a short region of sequence in the sigma1 tail
      predicted to form beta-sheet. These studies identify specific sequences that
      determine the capacity of reovirus to bind sialylated receptors and suggest a
      location for a sialic acid-binding domain. Furthermore, the results support a
      model in which type 3 sigma1 protein contains discrete receptor binding domains,
      one in the head and another in the tail that binds sialic acid.

PMID- 9032314
TI  - Construction of adenovirus vectors through Cre-lox recombination.
AB  - Two barriers prevent adenovirus-based vectors from having wide application. One
      is the difficulty of making new adenoviruses, and the second is the strong
      immunological reaction to viral proteins. Here we describe uses of Cre-lox
      recombination to overcome these problems. First, we demonstrate a simple method
      for constructing E1-substituted adenoviruses. Second, we demonstrate a method to
      construct adenovirus vectors carrying recombinant genes in place of all of the
      viral genes, so-called gutless adenovirus vectors. The pivotal feature in each
      method is the use of a negatively selected adenovirus named psi5. We engineered a
      cis-acting selection into psi5 by flanking its packaging site with loxP sites.
      When psi5 was grown in cells making a high level of Cre recombinase, the
      packaging site was deleted by recombination and the yield of psi5 was reduced to
      5% of the wild-type level. To make a new E1-substituted virus, we used psi5 as a
      donor virus and recombined it with a shuttle vector via a loxP site. The
      resulting recombinant virus has a single loxP site next to the packaging site and
      therefore outgrows psi5 in the presence of Cre recombinase. To make a gutless
      virus, we used psi5 as a helper virus. The only viral sequences included in the
      gutless vector are those needed in cis for its replication and packaging. We
      found that a loxP site next to the packaging site of the gutless virus was
      necessary to neutralize homologous recombination between psi5 and the gutless
      viruses within their packaging domains.

PMID- 9032315
TI  - The NPI-1/NPI-3 (karyopherin alpha) binding site on the influenza a virus
      nucleoprotein NP is a nonconventional nuclear localization signal.
AB  - Two cellular proteins, NPI-1 and NPI-3, were previously identified through their
      interaction with the influenza virus nucleoprotein (NP) by using the yeast two
      hybrid system. These proteins were then shown to act as general transport factors
      (karyopherin alpha) and nuclear pore-docking proteins to facilitate the transport
      of the NP and of viral RNA into the nucleus. The yeast two-hybrid assay has now
      been used to identify the specific domains on the NP that bind to the NPI
      proteins. Mutational analysis including alanine scanning identified the motifs
      SxGTKRSYxxM and TKRSxxxM, which are required for binding to NPI-1 and NPI-3,
      respectively. These sequences were shown to possess nuclear localization signal
      (NLS) activity following expression of fusion proteins in HeLa cells. These
      sequences represent a novel nonconventional NLS motif. Another NLS activity not
      mediated by the NPI binding sites is associated with noncontiguous sequences in
      the NP.

PMID- 9032317
TI  - Evolution of human immunodeficiency virus type 1 env sequence variation in
      patients with diverse rates of disease progression and T-cell function.
AB  - We examined the relationship between env sequence variation and disease
      progression in 10 human immunodeficiency virus type 1 (HIV-1)-seropositive
      subjects selected from a longitudinal cohort receiving zidovudine therapy. Five
      subjects were chosen for stable clinical status and CD4 counts (slow
      progressors), and five were selected for rapid clinical deterioration and CD4
      count decline (rapid progressors). The slow progressors had significantly lower
      plasma viral RNA loads and greater lymphoproliferative responses to mitogens than
      the rapid progressors. DNA sequences representing the C1 through C3 regions of
      env were amplified from two peripheral blood mononuclear cell DNA samples from
      each subject separated by an average of 2.5 years. Molecular clones of these
      amplicons were then sequenced, and DNA sequence and deduced amino acid sequence
      distances were compared. Inter-time point sequence comparison showed a higher
      rate of sequence evolution for the rapid progressors in three of five matched
      pairs of rapid progressors and slow progressors and for the slow progressors in
      the remaining two subject pairs. However, intra-time point sequence comparisons
      showed that four of five slow progressors developed a more diverse quasispecies
      over time and one showed no change. In contrast, four of five rapid progressors
      showed no change in quasispecies diversity over time and one showed a significant
      decrease in diversity. The overall C1 through C3 region quasispecies diversity in
      the slow progressors at baseline was lower than that for the rapid progressors,
      but this difference was not significant at the follow-up time points. These
      diversity relationships were obscured if sequence analyses were limited to the
      300-bp C2 to V3 region. Thus, HIV-1 quasispecies diversity increased over time in
      subjects with more functional immune systems.

PMID- 9032316
TI  - Human adenovirus early region 4 open reading frame 1 genes encode growth
      transforming proteins that may be distantly related to dUTP pyrophosphatase
      enzymes.
AB  - An essential oncogenic determinant of subgroup D human adenovirus type 9 (Ad9),
      which uniquely elicits estrogen-dependent mammary tumors in rats, is encoded by
      early region 4 open reading frame 1 (E4 ORF1). Whereas Ad9 E4 ORF1 efficiently
      induces transformed foci on the established rat embryo fibroblast cell line CREF,
      the related subgroup A Ad12 and subgroup C Ad5 E4 ORF1s do not (R. T. Javier, J.
      Virol. 68:3917-3924, 1994). In this study, we found that the lack of transforming
      activity associated with non-subgroup D adenovirus E4 ORF1s in CREF cells
      correlated with significantly reduced protein levels compared to Ad9 E4 ORF1 in
      these cells. In the human cell line TE85, however, the non-subgroup D adenovirus
      E4 ORF1s produced protein levels higher than those seen in CREF cells as well as
      transforming activities similar to that of Ad9 E4 ORF1, suggesting that all
      adenovirus E4 ORF1 polypeptides possess comparable cellular growth-transforming
      activities. In addition, searches for known proteins related to these novel viral
      transforming proteins revealed that the E4 ORF1 proteins had weak sequence
      similarity, over the entire length of the E4 ORF1 polypeptides, with a variety of
      organismal and viral dUTP pyrophosphatase (dUTPase) enzymes. Even though
      adenovirus E4 ORF1 proteins lacked conserved protein motifs of dUTPase enzymes or
      detectable enzymatic activity, E4 ORF1 and dUTPase proteins were predicted to
      possess strikingly similar secondary structure arrangements. It was also
      established that an avian adenovirus protein, encoded within a genomic location
      analogous to that of the human adenovirus E4 ORF1s, was a genuine dUTPase enzyme.
      Although no functional similarity was found for the E4 ORF1 and dUTPase proteins,
      we propose that human adenovirus E4 ORF1 genes have evolved from an ancestral
      adenovirus dUTPase and, from this structural framework, developed novel
      transforming properties.

PMID- 9032319
TI  - Adding an Rb-binding site to an N-terminally truncated simian virus 40 T antigen
      restores growth to high cell density, and the T common region in trans provides
      anchorage-independent growth and rapid growth in low serum concentrations.
AB  - The simian virus 40 large T antigen is sufficient to confer on cells multiple
      transformed cell growth characteristics, including growth to a high cell density,
      rapid growth in medium containing low serum concentrations, and anchorage
      independent growth. We showed previously that distinct regions of the protein
      were involved in conferring these properties and that removal of the first 127
      amino acids of T antigen abrogated all three activities. At least three large-T
      antigen transformation-related activities have been localized to that region:
      binding of the tumor suppressor gene product Rb and two independent activities
      contained within the common region shared by large T and small t antigens. The
      experiments described here were directed toward determining whether these were
      the only activities from the N terminus that were needed. To do so we
      reintroduced an Rb-binding region into the N-terminally truncated T antigen (T128
      708) and examined the growth properties of cells immortalized by it in the
      presence and absence of small t antigen, which can provide the T-common-region
      transformation-related activities in trans. We show that an Rb-binding region
      consisting of amino acids 101 to 118, when introduced into a heterologous site in
      T128-708, is capable of physically binding Rb and that binding is sufficient for
      cells expressing the protein to acquire the ability to grow to a high saturation
      density. However, in low-serum medium, the growth rate of the cells and maximal
      cell density are reduced relative to those of wild-type-T-antigen-expressing
      cells, and the cells cannot divide without anchorage. This result suggests that
      although Rb binding is sufficient in the context of T128-708 to confer growth to
      a high density, one or more other N-terminally located T-antigen activities are
      needed for cells to acquire the additional growth properties. Small t antigen in
      trans supplied those activities. These results indicate that the T-common-region
      activities and Rb binding are the only activities from the T-antigen N terminus
      needed to restore full transforming activity to the N-terminally truncated T
      antigen.

PMID- 9032318
TI  - Induction of AIDS by simian immunodeficiency virus lacking NF-kappaB and SP1
      binding elements.
AB  - Rhesus monkeys (Macaca mulatta) were infected with five strains of simian
      immunodeficiency virus (SIV) derived from SIVmac239 containing deletions (delta)
      or substitutions (subst) in NF-kappaB and Sp1 binding sites. We have shown
      previously that mutations in these regions still allow efficient SIVmac
      replication in primary lymphoid cell cultures (P. O. Ilyinskii and R. C.
      Desrosiers, J. Virol. 70:3118-3126, 1996). Two animals were inoculated
      intravenously with each mutant strain of SIVmac239: delta NFkappaB, delta Sp1234,
      delta NFkappaB delta Sp1234, substSp12, and substSp1234. All but one of the
      infected animals showed an early spike in plasma antigenemia, maintained high
      virus burdens, and had significant changes in lymphoid tissues, and six died with
      AIDS within the first 60 weeks of infection. One of the animals infected with the
      SIV strain delta NFkappaB delta Sp1234 showed lower levels of plasma antigenemia
      and lower virus burdens; the other animal infected with this same mutant strain
      died with AIDS 17 weeks after inoculation. No consistent novel mutations or
      reversions were detected in proviral sequences derived from the animals infected
      with the deletion mutants and the substSp12 mutant by 20 weeks postinfection.
      Point-mutated sequences were partially deleted in both animals infected with the
      substSp1234 strain. These results indicate that the NF-kappaB and Sp1 binding
      sites are not essential for the induction of AIDS by SIVmac239. They also provide
      indirect evidence for the importance of a novel enhancer element in the U3 region
      of the SIVmac long terminal repeat that is located immediately upstream of the NF
      kappaB binding site within the C-terminal region of the nef coding sequence.

PMID- 9032320
TI  - Analysis of recombinant adeno-associated virus packaging and requirements for rep
      and cap gene products.
AB  - Adeno-associated virus (AAV) is a human parvovirus currently being developed as a
      vector for gene therapy applications. Because the gene transfer vector commonly
      retains only the AAV terminal repeats, propagation of recombinant AAV (rAAV)
      requires that the viral replication (Rep) and capsid (Cap) proteins be supplied
      in trans. In an effort to optimize the production of these vectors, a panel of
      helper plasmids was constructed to determine if expression of the rep and/or cap
      genes is a limiting factor for rAAV packaging. Expression of the Rep and Cap
      proteins was increased by replacing the endogenous AAV promoters, p5 and p40,
      with the Rous sarcoma virus (RSV) long terminal repeat (LTR) and the
      cytomegalovirus immediate-early promoter, respectively. Increased synthesis of
      the Cap proteins resulted in an approximately 10-fold increase in the yield of
      rAAV, indicating that production of capsid proteins is one limiting factor for
      rAAV packaging. Expression of the rep gene from the RSV LTR not only failed to
      increase the yield of rAAV but also prevented activation of p40 transcription
      with adenovirus infection, resulting in a reduced level of capsid protein
      synthesis.

PMID- 9032321
TI  - The cytotoxic T-lymphocyte response to Sendai virus is unimpaired in the absence
      of gamma interferon.
AB  - Sendai virus is eliminated from the respiratory tract of gamma interferon (IFN
      gamma) -/- BALB/c mice with normal kinetics. The level of virus-specific
      cytotoxic T-lymphocyte (CTL) activity in the cell population recovered by
      bronchoalveolar lavage is unimpaired, the prevalence of interleukin-4 (IL-4)
      producing cells is increased, and the titers of virus-specific immunoglobulins
      IgG1 and IgG2b are higher in the IFN-gamma -/- mice. The emergence of this T
      helper 2 response profile in both lymphoid tissue and the pneumonic lung has no
      obvious deleterious consequences. Virus clearance is slightly delayed following
      depletion of the CD4+ subset, with the effect being similar in magnitude for IFN
      gamma -/- and +/+ mice. However, the generation of CTL precursors (CTLp) is
      diminished in the IFN-gamma -/- (but not +/+) mice in the absence of concurrent
      CD4+ T help. Apparently the clonal expansion of the CTLp population can be
      promoted either by a cytokine (perhaps IL-2) produced by the IFN-gamma -/- CD4+ T
      cells or by IFN-gamma made by other cell types in the +/+ mice.

PMID- 9032322
TI  - Rhesus macaques previously infected with simian/human immunodeficiency virus are
      protected from vaginal challenge with pathogenic SIVmac239.
AB  - Nontraumatic vaginal inoculation of rhesus macaques with a simian/human
      immunodeficiency virus (SIV/HIV) chimera containing the envelope gene from HIV-1
      89.6 (SHIV 89.6) results in systemic infection (Y. Lu, B. Brosio, M. Lafaile, J.
      Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045-3050, 1996).
      A total of five rhesus macaques have each been infected by exposure to at least
      three intravaginal inoculations of SHIV 89.6. The SHIV 89.6 infection is
      characterized by a transient viremia that evokes humoral and cellular immune
      responses to HIV and SIV antigens, but disease does not develop in animals
      infected with SHIV 89.6. To determine if a previous infection with SHIV 89.6 by
      vaginal inoculation could protect animals from vaginal challenge with pathogenic
      SIV, all five animals were intravaginally inoculated twice with pathogenic SIV
      mac239. After challenge, all of the SHIV-immunized animals had low or
      undetectable viral RNA levels in plasma compared to control animals. Three of the
      five of the SHIV-immunized animals remained virus isolation negative for more
      than 8 months, while two became virus isolation positive. The presence of SIV Gag
      specific cytotoxic T lymphocytes in peripheral blood mononuclear cells and SIV
      specific antibodies in cervicovaginal secretions at the time of challenge was
      associated with resistance to pathogenic SIV infection after vaginal challenge.
      These results suggest that protection from sexual transmission of HIV may be
      possible by effectively stimulating both humoral and cellular antiviral immunity
      in the systemic and genital mucosal immune compartments.

PMID- 9032323
TI  - The presence of host-derived HLA-DR1 on human immunodeficiency virus type 1
      increases viral infectivity.
AB  - Human immunodeficiency virus type 1 (HIV-1) incorporates several host cell
      components when budding out of the infected cell. One of the most abundant host
      derived molecules acquired by HIV-1 is the HLA-DR determinant of the major
      histocompatibility complex class II (MHC-II) molecules. The fact that CD4 is the
      natural ligand of MHC-II prompted us to determine if such virally embedded
      cellular components can affect the biology of the virus. Herein, we report for
      the first time that the incorporation of cellular HLA-DR1 within HIV-1 enhances
      its infectivity. This observation was made possible with virions bearing or not
      bearing on their surfaces host-derived HLA-DR1 glycoproteins. Such virus stocks
      were prepared by a transient-expression system based on transfection of 293T
      cells with a recombinant luciferase-encoding HIV-1 molecular clone along with
      plasmids encoding the alpha and beta chains of HLA-DR1. Cell-free virions
      recovered from transfected cells were shown to have efficiently incorporated host
      derived HLA-DR1 glycoproteins. Infectivity was increased by a factor of 1.6 to
      2.3 for virions bearing on their surfaces host-derived HLA-DR1. The observed
      enhancement of HIV-1 infectivity was independent of the virus stocks used and was
      seen in several T-lymphoid cell lines, in a premonocytoid cell line, and in
      primary peripheral blood mononuclear cells. Finally, we determined that the
      presence of virion-bound cellular HLA-DR1 is associated with faster kinetics of
      virus infection. Taken together, these results suggest that HLA-DR-1-bearing HIV
      1 particles had a greater infectivity per picogram of viral p24 protein than HLA
      DR1-free virions.

PMID- 9032324
TI  - Characterization of an ATP-dependent DNA ligase encoded by Chlorella virus PBCV
      1.
AB  - We report that Chlorella virus PBCV-1 encodes a 298-amino-acid ATP-dependent DNA
      ligase. The PBCV-1 enzyme is the smallest member of the covalent nucleotidyl
      transferase superfamily, which includes the ATP-dependent polynucleotide ligases
      and the GTP-dependent RNA capping enzymes. The specificity of PBCV-1 DNA ligase
      was investigated by using purified recombinant protein. The enzyme catalyzed
      efficient strand joining on a singly nicked DNA in the presence of magnesium and
      ATP (Km, 75 microM). Other nucleoside triphosphates or deoxynucleoside
      triphosphates could not substitute for ATP. PBCV-1 ligase was unable to ligate
      across a 2-nucleotide gap and ligated poorly across a 1-nucleotide gap. A native
      gel mobility shift assay showed that PBCV-1 DNA ligase discriminated between
      nicked and gapped DNAs at the substrate-binding step. These findings underscore
      the importance of a properly positioned 3' OH acceptor terminus in substrate
      recognition and reaction chemistry.

PMID- 9032325
TI  - Epstein-Barr virus immortalization: Notch2 interacts with CBF1 and blocks
      differentiation.
AB  - EBNA2 is essential for immortalization of B cells by Epstein-Barr virus. EBNA2 is
      tethered to responsive promoters through a cellular factor, CBF1. CBF1 also binds
      to the activated form of mammalian Notch1, providing a linkage between EBNA2
      function and Notch signalling. However, Notch2 is the predominant form expressed
      in spleen. The degree to which these Notch homologs are functionally convergent
      is not known. We present evidence that Notch2 also signals through CBF1. As is
      the case for Notch1, Notch2 interacted with the minimal repression domain of CBF1
      and was targeted to CBF1 through the intracellular, subtransmembrane domain.
      Additional characterization suggested that the interaction domain of Notch may be
      bipartite. The intracellular domain of Notch2 (Notch2IC) located to the nucleus.
      This activated form of Notch2 transactivated expression of a target gene
      containing upstream CBF1 binding sites. The use of CBF1 mutants carrying amino
      acid substitutions in the transcriptional repression domain revealed that
      activation of gene expression by Notch2 is also based on masking of CBF1-mediated
      repression. Targeting of Notch1 and targeting of Notch2 were found to be
      identical and distinguishable from targeting by EBNA2. Mutation of CBF1 at codons
      249 to 251 abolished interaction with both Notch proteins but not with EBNA2. In
      a biological examination of Notch2 function in muscle cells, Notch2IC activated
      endogenous HES-1 gene expression and blocked muscle cell differentiation.
      Overall, the data imply that at least a subset of the intracellular events
      following signalling in cells expressing Notch2 are common to those in Notch1
      expressing cells. The concept that EBNA2 functions by mimicking Notch signalling
      is therefore viable whether cells are expressing Notch1 or Notch2.

PMID- 9032326
TI  - Episodic evolution mediates interspecies transfer of a murine coronavirus.
AB  - Molecular mechanisms permitting the establishment and dissemination of a virus
      within a newly adopted host species are poorly understood. Mouse hepatitis virus
      (MHV) strains (MHV-A59, MHV-JHM, and MHV-A59/MHV-JHM) were passaged in mixed
      cultures containing progressively increasing concentrations of nonpermissive
      Syrian baby hamster kidney (BHK) cells and decreasing concentrations of
      permissive murine DBT cells. From MHV-A59/MHV-JHM mixed infection, variant
      viruses (MHV-H1 and MHV-H2) which replicated efficiently in BHK cells were
      isolated. Under identical treatment conditions, the parental MHV-A59 or MHV-JHM
      strains failed to produce infectious virus or transcribe detectable levels of
      viral RNA or protein. The MHV-H isolates were polytrophic, replicating
      efficiently in normally nonpermissive Syrian hamster smooth muscle (DDT-1),
      Chinese hamster ovary (CHO), human adenocarcinoma (HRT), primate kidney (Vero),
      and murine 17Cl-1 cell lines. Little if any virus replication was detected in
      feline kidney (CRFK) and porcine testicular (ST) cell lines. The variant virus,
      MHV-H2, transcribed seven mRNAs equivalent in relative abundance and size to
      those synthesized by the parental virus strains. MHV-H2 was an RNA recombinant
      virus containing a crossover site in the S glycoprotein gene. At the molecular
      level, episodic evolution and positive Darwinian natural selection were apparent
      within the MHV-H2 S and HE glycoprotein genes. These findings differ from the
      hypothesis that neutral changes are the predominant feature of molecular
      evolution and argue that changing ecologies actuate episodic evolution in the MHV
      spike glycoprotein genes that govern interspecies transfer and spread into
      alternative hosts.

PMID- 9032327
TI  - Human T-cell leukemia virus type 1 Tax releases cell cycle arrest induced by
      p16INK4a.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein causes cellular
      transformation by deregulating important cellular processes such as DNA repair,
      transcription, signal transduction, proliferation, and growth. Although it is
      clear that normal cell cycle control is deregulated during HTLV-1-induced
      cellular transformation, the effects of Tax on cell cycle control are not well
      understood. Flow cytometric analyses of human T cells indicate that cell cycle
      arrest in late G1, at or before the G1/S restriction point, by p16INK4a is
      relieved by Tax. Furthermore, Tax-dependent stimulation of 5-bromo-2'
      deoxyuridine incorporation and transcriptional activation is inhibited by
      p16INK4a. This result suggests that p16INK4a is able to block Tax-dependent
      stimulation of DNA synthesis and cell cycle progression into S phase. In vitro
      binding assays with recombinant glutathione S-transferase fusion proteins and
      [35S]methionine-labeled proteins indicate that Tax binds specifically with
      p16INK4a but not with either p21cip1 or p27kip1. Furthermore, sequential
      immunoprecipitation assays with specific antisera and [35S]methionine-labeled
      cell lysates subsequent to coexpression with Tax and p16INK4a indicate that the
      two proteins form complexes in vivo. Immunocomplex kinase assays with cyclin
      dependent kinase 4 antiserum indicate that Tax blocks the inhibition of cdk4
      kinase activity by p16INK4a. This study identifies p16INK4a as a novel cellular
      target for Tax and suggests that the inactivation of p16INK4a function is a
      mechanism of cell cycle deregulation by Tax.

PMID- 9032329
TI  - Transrepression of lck gene expression by human T-cell leukemia virus type 1
      encoded p40tax.
AB  - To understand the mechanism of p56lck protein downregulation observed in human T
      cells infected by human T-cell leukemia virus type 1 (HTLV-1), we have
      investigated the ability of the 3' end of the HTLV-1 genome as well as that of
      the tax and rex genes to modulate p56lck protein expression and p56lck mRNA
      synthesis. By using Jurkat T cells stably transfected with constructs that
      expressed either the 3' end of the HTLV-1 genome (JK C11-pMTEX), the tax gene
      (JK52-Tax) or the rex gene (JK9-Rex), we found that the expression of p40tax
      (Tax) was sufficient to modulate p56lck protein expression. Similarly, we found
      that the expression of the mRNA which encoded p56lck was repressed in Jurkat T
      cells which expressed Tax. This downregulation was shown to be proportional to
      the amount of tax mRNA found in the transfected cells, as evidenced by
      experiments that used cells (JPX-9) stably transfected with a tax gene driven by
      a cadmium-inducible promoter. Furthermore, cadmium induction of Tax in JPX-9
      cells transiently transfected with a construct containing the chloramphenicol
      acetyltransferase (CAT) gene under control of the lck distal promoter (lck DP
      CAT) resulted in the downregulation of CAT gene expression. In contrast, cadmium
      induction of Tax in JPX-9 cells transiently transfected with a CAT construct
      driven by a lck DP with a deletion extending from position -259 to -253 (a
      sequence corresponding to a putative E-Box) did not modulate CAT gene expression,
      suggesting that the effect of Tax on p56lck is mediated through an E-Box binding
      protein.

PMID- 9032328
TI  - A single 13-kilobase divergent locus in the Kaposi sarcoma-associated herpesvirus
      (human herpesvirus 8) genome contains nine open reading frames that are
      homologous to or related to cellular proteins.
AB  - Two small fragments of a novel human gammaherpesvirus genome known as Kaposi's
      sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (HHV-8) have been
      shown to be present in virtually all AIDS and non-AIDS KS lesions, as well as in
      body cavity-based lymphomas (BCBL) and in multicentric Castleman's disease. We
      have extended those studies by identifying and sequencing a third fragment of HHV
      8 DNA encoding a viral thymidylate synthetase (TS) gene. Use of this viral TS
      fragment as a probe led to the identification and mapping of a cluster of
      overlapping phage lambda clones from a BCBL tumor DNA genomic library that
      spanned 48 kb on the left-hand side of the HHV-8 genome between the equivalents
      of open reading frame 6 (ORF6) and ORF31 of herpesvirus saimiri (HVS). DNA
      sequencing of a 17-kb segment encompassing a gammaherpesvirus divergent locus (DL
      B) between ORF11 and ORF17 revealed the presence of nine viral ORFs with
      predicted gene products related to cellular proteins. These include the complete
      TS gene and a dihydrofolate reductase (DHFR) gene, four novel cytokine genes
      (encoding viral interleukin-6, viral MIP-1A, viral MIP-1B, and BCK) that have not
      previously been found to be encoded by a virus, and a bcl-2 homolog. This region
      in HHV-8 also contains the T1.1 abundant lytic cycle nuclear RNA gene and
      encompasses two genes (or exons) encoding proteins with C4HC3 zinc finger domains
      of the PHD/leukemia-associated protein subtype. The latter are related to the
      spliced immediate-early IE1 protein of the gamma-2 class herpesvirus bovine
      herpesvirus type 4 and a similar motif found in HVS ORF12. Although genes for TS
      and DHFR enzymes are also encoded by HVS (ORF70 and ORF2), both occur at
      different genomic loci than in HHV-8, and the HHV-8 DHFR protein is much farther
      diverged from human DHFR than is the HVS version, implying that they were
      probably acquired as host cell cDNAs by independent evolutionary events.
      Transcripts from the IE1-A, IE1-B, DHFR, and MIP-1B genes were all detected by
      Northern blot hybridization analysis in a BCBL cell line at 12 h after induction
      with butyrate but were not present before induction, indicating that these are
      all primarily lytic cycle genes. We conclude that the DL-B locus of
      gammaherpesviruses displays considerably more variability that previously
      appreciated and that expression of many of these genes is likely to have
      important implications for HHV-8 biology and therapy.

PMID- 9032330
TI  - Kaposi's sarcoma-associated herpesvirus encodes a functional cyclin.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus 8)
      is consistently found in Kaposi's sarcoma lesions and in body-cavity-based
      lymphomas. A 17-kb KSHV lambda clone was obtained directly from a Kaposi's
      sarcoma lesion. DNA sequence analysis of this clone identified an open reading
      frame which has 32% amino acid identity and 53% similarity to the virus-encoded
      cyclin (v-cyclin) of herpesvirus saimiri (HVS) and 31% identity and 53%
      similarity to human cellular cyclin D2. This KSHV open reading frame was shown to
      encode a 29- to 30-kDa protein with the properties of a v-cyclin. KSHV v-cyclin
      protein was found to associate predominantly with cdk6, a cellular cyclin
      dependent kinase known to interact with cellular type D cyclins and HVS v-cyclin.
      The KSHV v-cyclin was also found to associate weakly with cdk4. KSHV v-cyclin
      cdk6 complexes strongly phosphorylated glutathione S-transferase-Rb fusion
      protein and histone H1 as substrates in vitro. Thus, KSHV v-cyclin resembles the
      v-cyclin of the T-lymphocyte-transforming HVS in its specificity for association
      with cdk6 and in its ability to strongly activate cdk6 protein kinase activity.

PMID- 9032332
TI  - Distinct domains of adenovirus E1A interact with specific cellular factors to
      differentially modulate human immunodeficiency virus transcription.
AB  - Transcription of human immunodeficiency virus (HIV) type 1 and other viruses is
      regulated by the transcription factor NF-kappaB, which interacts with the
      multifunctional cellular protein p300. p300, originally identified by its ability
      to bind adenovirus early region 1A (E1A), has also been shown to regulate HIV
      transcription through its interaction with NF-kappaB. The 13S form of E1A
      activates HIV gene expression, while the 12S form represses its transcription. In
      this report, we have investigated whether these divergent effects of E1A are
      dependent upon common or distinct cellular cofactors, including p300, pRb, and
      the TATA box-binding protein (TBP). Unlike activation in the absence of E1A,
      cooperative stimulation of HIV gene expression by 13S E1A and RelA was
      independent of the ability of E1A to bind p300 but was critically dependent on
      the E1A CR3 region which associates with TBP. In contrast, inhibition of basal
      HIV gene expression by the 12S form of E1A was dependent on p300 but not pRb or
      TBP. Interestingly, mutation of the CR2 region of 12S E1A responsible for pRb
      binding abolished the repression of HIV transcription stimulated by tumor
      necrosis factor alpha, suggesting that repression of cytokine-activated
      transcription involves cofactors different from those used in unstimulated cells.
      Repression and activation of HIV transcription by different forms of E1A are
      mediated by distinct sets of cellular cofactors. These findings suggest that E1A
      has evolved to interact by alternative mechanisms with a transcriptional
      coactivator and its associated cofactors to differentially modulate cellular and
      viral gene expression.

PMID- 9032331
TI  - Double-stranded RNA is a trigger for apoptosis in vaccinia virus-infected cells.
AB  - The vaccinia virus E3L gene codes for double-stranded RNA (dsRNA) binding
      proteins which can prevent activation of the dsRNA-dependent, interferon-induced
      protein kinase PKR. Activated PKR has been shown to induce apoptosis in HeLa
      cells. HeLa cells infected with vaccinia virus with the E3L gene deleted have
      also been shown to undergo apoptosis, whereas HeLa cells infected with wild-type
      vaccinia virus do not. In this report, using virus recombinants expressing mutant
      E3L products or alternative dsRNA binding proteins, we show that suppression of
      induction of apoptosis correlates with functional binding of proteins to dsRNA.
      Infection of HeLa cells with ts23, which leads to synthesis of increased dsRNA at
      restrictive temperature, induced apoptosis at restrictive but not permissive
      temperatures. Treatment of cells with cytosine arabinoside, which blocks the late
      buildup of dsRNA in vaccinia virus-infected cells, prevented induction of
      apoptosis by vaccinia virus with E3L deleted. Cells transfected with dsRNA in the
      absence of virus infection also underwent apoptosis. These results suggest that
      dsRNA is a trigger that can initiate a suicide response in virus-infected and
      perhaps uninfected cells.

PMID- 9032333
TI  - CCAAT displacement protein, a regulator of differentiation-specific gene
      expression, binds a negative regulatory element within the 5' end of the human
      papillomavirus type 6 long control region.
AB  - We have reported previously that a 636-bp fragment spanning the 5' two-thirds of
      the human papillomavirus type 6 (HPV6)-W50 long control region (LCR) functions as
      a transcriptional silencer (A. Farr, S. Pattison, B.-S. Youn, and A. Roman, J.
      Gen. Virol. 76:827-835, 1995). We have utilized nested deletion analyses to
      implicate a 66-bp sequence which appears to be critical for this activity. A
      comparison of the transcriptional regulatory activities of the LCRs of HPV6-W50
      and HPV6b (which has a 94-bp deletion, resulting in the elimination of the 66-bp
      sequence) indicates that sequences within the 94-bp region negatively regulate
      the activity of the intact HPV6 LCR. Two sequence-specific DNA-protein
      interactions were visualized via electrophoretic mobility shift assays. One of
      the binding events is mediated by the transcriptional repressor CCAAT
      displacement protein (CDP), a factor which is active in undifferentiated cells
      but inactive in terminally differentiated cells. This conclusion is based on the
      following three lines of evidence: (i) a consensus CDP binding site
      oligonucleotide serves as a competitor in band shift assays, (ii) the band shift
      complex is not seen when a CDP-negative nuclear extract is used, and (iii) anti
      CDP antiserum specifically inhibits the binding. These studies identify a DNA
      protein interaction occurring within the 5' end of the LCR which may be important
      in maintaining the tight link between keratinocyte differentiation and HPV gene
      expression.

PMID- 9032335
TI  - Repression of host RNA polymerase II transcription by herpes simplex virus type
      1.
AB  - Lytic infection of mammalian cells with herpes simplex virus type 1 (HSV-1)
      results in rapid repression of host gene expression and selective activation of
      the viral genome. This transformation in gene expression is thought to involve
      repression of host transcription and diversion of the host RNA polymerase (RNAP
      II) transcription machinery to the viral genome. However, the extent of virus
      induced host transcription repression and the mechanisms responsible for these
      major shifts in transcription specificities have not been examined. To determine
      how HSV-1 accomplishes repression of host RNAP II transcription, we assayed
      transcription patterns on several cellular genes in cells infected with mutant
      and wild-type HSV-1. Our results suggest that HSV-1 represses RNAP II
      transcription on most cellular genes. However, each cellular gene we examined
      responds differently to the transcription repressive effects of virus infection,
      both quantitatively and with respect to the involvement of viral gene products.
      Virus-induced shutoff of host RNAP II transcription requires expression of
      multiple immediate-early genes. In contrast, expression of delayed-early and late
      genes and viral DNA replication appear to contribute little to repression of host
      cell RNAP II transcription. Modification of RNAP II to the intermediately
      phosphorylated (II(I)) form appears unlinked to virus-induced repression of host
      cell transcription. However, full repression of host transcription is correlated
      with depletion of the hyperphosphorylated (IIO) form of RNAP II.

PMID- 9032334
TI  - Founder virus population related to route of virus transmission: a determinant of
      intrahost human immunodeficiency virus type 1 evolution?
AB  - We and others have shown that in individual human immunodeficiency virus type 1
      (HIV-1) infection, the adaptive evolution of HIV-1 is influenced by host immune
      competence. In this study, we tested the hypothesis that in addition to selective
      forces operating within the host, transmission bottlenecks have an impact on HIV
      1 intrahost evolution. Therefore, we studied the intrahost evolution of the V3
      region of the external glycoprotein gp120 of HIV-1 during the 3- and 5-year
      periods following seroconversion after parenteral versus sexual (male-to-male)
      transmission in 41 participants of the Amsterdam prospective cohorts of
      homosexual men (n = 31) and intravenous drug users (IVDUs; n = 10) who were AIDS
      free and had comparable numbers of CD4+ cells. We observed that HIV-1 strains in
      homosexual men accumulated over 5 years more nonsynonymous substitutions within
      the V3 loop than HIV-1 strains in IVDUs as a result of lower rates of
      nonsynonymous evolution in both the initial 3-year period from seroconversion and
      the following 2-year period as well as a larger proportion of nonsynonymous back
      substitutions in IVDUs. The mean numbers of synonymous substitutions did not
      differ between the two risk groups. Since HIV-1 strains in IVDUs could be
      distinguished from the viruses of homosexual men based on several nucleotide
      substitutions of which the most conserved is a synonymous substitution at the tip
      of the V3 loop (GGC pattern), we studied whether the founder virus population
      itself has an impact on the intrahost evolution of HIV-1. The mean number of
      nonsynonymous substitutions accumulated over 5 years within the V3 loop was lower
      in 10 IVDUs infected by the HIV-1 strains with the GGC signature than in 4 IVDUs
      infected by HIV-1 strains lacking this pattern, while the mean numbers of
      synonymous substitutions were similar in the two groups.

PMID- 9032336
TI  - Human immunodeficiency virus type 1 envelope glycoprotein oligomerization
      requires the gp41 amphipathic alpha-helical/leucine zipper-like sequence.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)
      oligomerization was investigated by coexpressing wild-type and truncated envelope
      glycoproteins to determine the minimum sequence required for mutant-wild-type
      hetero-oligomerization. The gp41 putative amphipathic alpha-helix, Leu-550 to Leu
      582, was essential for hetero-oligomer formation. Alanine substitution of 9 of
      the 10 residues composing the gp41 amphipathic alpha-helix 4-3 hydrophobic repeat
      sequence was required to inhibit mutant-wild-type hetero-oligomerization and to
      render the envelope glycoprotein precursor, gp160, monomeric. This indicates that
      multiple hydrophobic contacts contribute to the stable envelope glycoprotein
      oligomeric structure. Single alanine substitutions within the hydrophobic repeat
      sequence did not affect gp160 oligomeric structure but abolished syncytium
      forming function. Some mutations also diminished gp160 processing efficiency and
      the association between gp120 and gp41 in a position-dependent manner. These
      results indicate that the gp41 amphipathic alpha-helix 4-3 hydrophobic repeat
      sequence plays a central role in HIV-1 envelope glycoprotein oligomerization and
      fusion function.

PMID- 9032338
TI  - In vivo compartmentalization of human immunodeficiency virus: evidence from the
      examination of pol sequences from autopsy tissues.
AB  - High rates of mutation and replication of human immunodeficiency virus (HIV)
      allow for the continuous generation of diverse genetic variants in vivo.
      Selective pressures within the microenvironments of different anatomic
      compartments result in the emergence of dominant quasispecies which can be
      distinguished by their envelope sequences. It is not known whether comparable
      tissue-specific selective pressures lead to the independent evolution of pol
      sequences within different tissue compartments, nor is it known how differing
      rates of virus turnover in tissues might affect the pace of such evolution. These
      issues are of importance for the formulation of a model for the emergence of drug
      resistance in vivo and for a general understanding of virus trafficking and virus
      turnover. Regions of the HIV type 1 reverse transcriptase (RT) which carry the
      majority of the known resistance codons to RT inhibitors (700 nucleotides from
      each clone) were cloned and sequenced directly from autopsied brain, spleen, and
      lymph node specimens from four subjects who had received zidovudine therapy.
      Clones from proviral DNA (143) and from viral cDNA (14) were analyzed. In three
      of four subjects, a discordance in distribution of resistance codons was noted.
      Moreover, brain-derived sequences appeared to be phylogenetically distinct from
      spleen- and lymph node-derived sequences even after exclusion of resistance
      codons from analysis. In each case, evidence for differential immune selective
      pressure, based on comparison of inferred amino acid sequences corresponding to
      known major histocompatibility complex class I cytotoxic T-lymphocyte epitopes,
      was found. These observations support the concept of anatomically distinct,
      independently evolving quasispecies (virodemes).

PMID- 9032337
TI  - Position dependence of functional hairpins important for human immunodeficiency
      virus type 1 RNA encapsidation in vivo.
AB  - At least two hairpins in the 5' untranslated leader region, stem-loops 1 and 3
      (SL1 and SL3), contribute to human immunodeficiency virus type 1 RNA
      encapsidation in vivo. We used a competitive assay, which measures the relative
      encapsidation efficiency of mutant viral RNA in the presence of competing wild
      type RNA, to compare the contributions of SL1, SL3, and two adjacent secondary
      structures, SL2 and SL4, to encapsidation. SL2 is not required for RNA
      encapsidation, while SL1, SL3, and SL4 all contribute approximately equally to
      encapsidation. To determine whether these hairpins function in a position
      dependent manner, we interchanged the positions of two of these stem-loop
      structures. This resulted in substantial diminution of encapsidation, indicating
      that the secondary structures that comprise E, the encapsidation signal, function
      only in their correct contexts. Mutation of nucleotides flanking SL1 and SL3 had
      little effect on encapsidation. We also showed that SL1, while present on both
      genomic and subgenomic viral RNAs, nonetheless contributes to selective
      encapsidation of genomic RNA. Taken together, these data are consistent with the
      formation of a higher-order RNA structure, partially composed of SL1, SL3, and
      SL4, that functions to effect concurrent encapsidation of full-length RNA and
      exclusion of subgenomic RNA. Finally, it has been reported that E is required for
      efficient translation of Gag mRNA in vivo. However, we have found that a variety
      of mutants, including a mutant lacking the entire region encompassing SL1, SL2,
      and SL3, still produce RNAs that are efficiently translated. These data indicate
      that E is unlikely to contribute to efficient Gag mRNA translation in vivo.

PMID- 9032339
TI  - Ultrastructural analysis of the replication cycle of pseudorabies virus in cell
      culture: a reassessment.
AB  - We reinvestigated major steps in the replicative cycle of pseudorabies virus
      (PrV) by electron microscopy of infected cultured cells. Virions attached to the
      cell surface were found in two distinct stages, with a distance of 12 to 14 nm or
      6 to 8 nm between virion envelope and cell surface, respectively. After fusion of
      virion envelope and cell membrane, immunogold labeling using a monoclonal
      antibody against the envelope glycoprotein gE demonstrated a rapid drift of gE
      from the fusion site, indicating significant lateral movement of viral
      glycoproteins during or immediately after the fusion event. Naked nucleocapsids
      in the cytoplasm frequently appeared close to microtubules prior to transport to
      nuclear pores. At the nuclear pore, nucleocapsids invariably were oriented with
      one vertex pointing to the central granulum at a distance of about 40 nm and
      viral DNA appeared to be released via the vertex region into the nucleoplasm.
      Intranuclear maturation followed the typical herpesvirus nucleocapsid
      morphogenesis pathway. Regarding egress, our observations indicate that primary
      envelopment of nucleocapsids occurred at the inner leaflet of the nuclear
      membrane by budding into the perinuclear cisterna. This nuclear membrane-derived
      envelope exhibited a smooth surface which contrasts the envelope obtained by
      putative reenvelopment at tubular vesicles in the Golgi area which is
      characterized by distinct surface projections. Loss of the primary envelope and
      release of the nucleocapsid into the cytoplasm appeared to occur by fusion of
      envelope and outer leaflet of the nuclear membrane. Nucleocapsids were also found
      engulfed by both lamella of the nuclear membrane. This vesiculation process
      released nucleocapsids surrounded by two membranes into the cytoplasm. Our data
      also indicate that fusion between the two membranes then leads to release of
      naked nucleocapsids in the Golgi area. Egress of virions appeared to occur via
      transport vesicles containing one or more virus particles by fusion of vesicle
      and cell membrane. Our data thus support biochemical data and mutant virus
      studies of (i) two steps of attachment, (ii) the involvement of microtubules in
      the transport of nucleocapsids to the nuclear pore, and (iii) secondary
      envelopment in the trans-Golgi area in PrV infection.

PMID- 9032340
TI  - Altered Rous sarcoma virus Gag polyprotein processing and its effects on particle
      formation.
AB  - Proteolytic processing of the Rous sarcoma virus (RSV) Gag precursor was altered
      in vivo through the introduction of amino acid substitutions into either the
      polyprotein cleavage junctions or the PR coding sequence. Single amino acid
      substitutions (V(P2)S and P(P4)G), which are predicted from in vitro peptide
      substrate cleavage data to decrease the rate of release of PR from the Gag
      polyprotein, were placed in the NC portion of the NC-PR junction. These
      substitutions do not affect the efficiency of release of virus-like particles
      from COS cells even though recovered particles contain significant amounts of
      uncleaved Pr76gag in addition to mature viral proteins. Single amino acid
      substitutions (A(P3)F and S(P1)Y), which increase the rate of PR release from
      Gag, also do not affect budding of virus-like particles from cells. Substitution
      of the inefficiently cleaved MA-p2 junction sequence in Gag by eight amino acids
      from the rapidly cleaved NC-PR sequence resulted in a significant increase in
      cleavage at the new MA-p2 junction, but again without an effect on budding.
      However, decreased budding was observed when the A(P3)F or S(P1)Y substitution
      was included in the NC-PR junction sequence between the MA and p2 proteins. A
      budding defect was also caused by substitution into Gag of a PR subunit
      containing three amino acid substitutions (R105P, G106V, and S107N) in the
      substrate binding pocket that increase the catalytic activity of PR. The defect
      appears to be the result of premature proteolytic processing that could be
      rescued by inactivating PR through substitution of a serine for the catalytic
      aspartic acid residue. This budding defect was also rescued by single amino acid
      substitutions in the NC-PR cleavage site which decrease the rate of release of PR
      from Gag. A similar budding defect was caused by replacing the Gag PR with two PR
      subunits covalently linked by four glycine residues. In contrast to the defect
      caused by the triply substituted PR, the budding defect observed with the linked
      PR dimer could not be rescued by NC-PR cleavage site mutations, suggesting that
      PR dimerization is a limiting step in the maturation process. Overall, these
      results are consistent with a model in which viral protein maturation occurs
      after PR subunits are released from the Gag polyprotein.

PMID- 9032342
TI  - Reovirus infection and tissue injury in the mouse central nervous system are
      associated with apoptosis.
AB  - Reovirus serotype 3 strains infect neurons within specific regions of the
      neonatal mouse brain and produce a lethal meningoencephalitis. Viral replication
      and pathology colocalize and have a predilection for the cortex, hippocampus, and
      thalamus. We have shown previously that infection of cultured fibroblasts and
      epithelial cells with reovirus type 3 Dearing (T3D) and other type 3 reovirus
      strains results in apoptotic cell death, suggesting that apoptosis is a mechanism
      of cell death in vivo. We now report that T3D induces apoptosis in infected mouse
      brain tissue. To determine whether reovirus induces apoptosis in neural tissues,
      newborn mice were inoculated intracerebrally with T3D, and at various times after
      inoculation, brain tissue was assayed for viral antigen by immunostaining and
      apoptosis was identified by DNA oligonucleosomal laddering and in situ terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling. Cells were also
      stained with cresyl violet to detect morphological changes characteristic of
      apoptosis, including chromatin condensation and cell shrinkage. DNA laddering was
      detected in T3D- but not in mock-infected brain tissue. Apoptotic cells were
      restricted to the same regions of the brain in which infected cells and tissue
      damage were observed. These findings suggest that virus-induced apoptosis is a
      mechanism of cell death, tissue injury, and mortality in reovirus-infected mice.
      The correlation between apoptosis and pathogenesis in vivo identifies apoptosis
      as a potential target for molecular and pharmacological strategies designed to
      curtail or prevent diseases resulting from induction of this cell death pathway.

PMID- 9032341
TI  - Functional dissection of the Moloney murine leukemia virus envelope protein gp70.
AB  - The envelope protein of Moloney murine leukemia virus (Mo-MLV) is a complex
      glycoprotein that mediates receptor binding and entry via fusion with cell
      membranes. By using a series of substitution mutations and truncations in the Mo
      MLV external envelope surface protein gp70, we have identified regions important
      for these processes. Firstly, truncations of gp70 revealed that the minimal
      continuous receptor-binding region is amino acids 9 to 230, in broad agreement
      with other studies. Secondly, within this region there are two key basic amino
      acids, Arg-83 and Arg-95, that are essential for receptor binding and may
      interact with a negatively charged residue(s) or with the pi electrons of the
      aromatic ring on a hydrophobic residue(s) in the basic amino acid transporter
      protein that is the Mo-MLV ecotropic receptor. Finally, we showed that outside
      the minimal receptor-binding region at amino acids 2 to 8, there is a region that
      is essential for postbinding fusion events.

PMID- 9032343
TI  - The hydrophobic pocket of cyclophilin is the binding site for the human
      immunodeficiency virus type 1 Gag polyprotein.
AB  - Completion of an early step in the human immunodeficiency virus type 1 (HIV-1)
      life cycle requires incorporation into virions of the cellular peptidyl-prolyl
      isomerase cyclophilin A (CyPA) by the Gag polyprotein. Elucidation of the
      biochemical role of CyPA would be aided by a detailed analysis of the genetic
      requirements for the formation of the Gag-CyPA complex; previous experiments have
      demonstrated the requirement for a critical proline and the immediately preceding
      glycine, located within the capsid domain of Gag, but nothing is known about the
      necessary CyPA residues. Cyclophilins possess a hydrophobic pocket where proline
      containing peptide substrates and the immunosuppressive drug cyclosporine A bind.
      In this study, we engineered five CyPA mutations, each of which alters a residue
      that contributes to the hydrophobic pocket. Compared with the wild-type protein,
      all of the mutants drastically reduced CyPA binding to HIV-1 Gag and similarly
      inhibited CyPA incorporation into virions. In addition, we demonstrated that
      previously reported differences between the Gag-binding properties of CyPA and
      CyPB are due to adventitious association involving residues in the signal
      sequence of CyPB and that the core domain of CyPB interacts with Gag in a fashion
      which is indistinguishable from that of CyPA. These studies indicate that, as
      with other proline-containing peptides or cyclosporine A, HIV-1 Gag directly
      contacts residues in the hydrophobic pocket of CyPA.

PMID- 9032344
TI  - Constitutive expression of p50 homodimer in freshly isolated human monocytes
      decreases with in vitro and in vivo differentiation: a possible mechanism
      influencing human immunodeficiency virus replication in monocytes and mature
      macrophages.
AB  - Human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in vitro
      in differentiated macrophages than in freshly isolated monocytes. We investigated
      whether this may be partly explained by changes in expression of NF-kappaB with
      monocyte differentiation. We demonstrated that constitutive expression of NF
      kappaB in primary human monocytes changed significantly with differentiation in
      vitro to monocyte-derived macrophages (MDMs) and differentiation in vivo to
      alveolar macrophages (AMs). Freshly isolated monocytes constitutively expressed
      high levels of transcriptionally inactive p50 homodimer which decreased with time
      in culture in favor of the transcriptionally active p50/p65 and p50/RelB
      heterodimers. As in MDMs, AMs constitutively expressed p50/p65 and p50/RelB
      although at lower levels. HIV infection of fresh monocytes failed to induce
      p50/p65 as seen in MDMs. The replacement of p50 homodimers with transcriptionally
      active heterodimers following time in culture may partially explain the
      progressive increase in susceptibility of monocytes to HIV infection during in
      vitro culture. The change in NF-kappaB components with monocyte differentiation
      in vivo may also explain the different transcriptional activities of these cell
      populations in HIV-infected individuals.

PMID- 9032345
TI  - The role of ATF in regulating the human cytomegalovirus DNA polymerase (UL54)
      promoter during viral infection.
AB  - Previous analysis of the human cytomegalovirus (HCMV) DNA polymerase (UL54) early
      gene promoter demonstrated that transcriptional activation of this gene is
      dependent upon the interaction of cellular transcription factors with viral
      transactivators (J. A. Kerry, M. A. Priddy, T. Y. Jervey, C. P. Kohler, T. L.
      Staley, C. D. Vanson, T. R. Jones, A. C. Iskenderian, D. G. Anders, and R. M.
      Stenberg, J. Virol. 70:373-382, 1996). A sequence element, IR1, was shown to be
      the primary regulatory element of this promoter in transient assays. However,
      assessment of this element in the context of the viral genome revealed IR1
      independent activation at late times after infection. To extend these studies, we
      aim to identify additional sequence elements involved in the activation of the
      UL54 promoter. Our present studies demonstrate that the level of binding of
      proteins to the ATF site in the UL54 promoter is enhanced by viral infection.
      Furthermore this increase is sensitive to treatment with phosphonoacetic acid
      (PAA), a DNA synthesis inhibitor. These data suggest that the increase in the
      level of ATF binding activity is regulated, either directly or indirectly, by
      HCMV late gene expression. By using specific antibodies, we determined that ATF-1
      was a major component of the proteins binding to the UL54 ATF site at late times.
      In addition, we have demonstrated direct binding of recombinant ATF-1 to the UL54
      ATF site. To assess the biological significance of these events, a recombinant
      virus construct was generated that contained the UL54 promoter with a mutation in
      the ATF site regulating expression of the chloramphenicol acetyltransferase (CAT)
      reporter gene inserted between open reading frames US9 and US10. Analysis of this
      virus (RVATFmCAT) revealed that mutation of the ATF site does not alter the
      kinetics of UL54 promoter activation. However, levels of CAT mRNA and activity
      were reduced by 5- to 10-fold compared to those of the wild-type promoter at all
      stages of infection. These findings indicate that ATF-1 can regulate the levels
      of UL54 promoter activity at both early and late times. Furthermore, these
      results imply that HCMV can regulate the activity of cellular factors involved in
      early gene regulation.

PMID- 9032346
TI  - Mutational analyses of the intergenic dinucleotide and the transcriptional start
      sequence of vesicular stomatitis virus (VSV) define sequences required for
      efficient termination and initiation of VSV transcripts.
AB  - We have used dicistronic vesicular stomatitis virus (VSV) minigenomes to dissect
      the functional importance of the nontranscribed intergenic dinucleotide and the
      conserved transcription start sequence found at the beginning of all VSV genes.
      The minigenomes were generated entirely from cDNA and contained the G and M
      protein genes, flanked by the leader and trailer regions from the Indiana
      serotype of VSV. All mutations were made either within the nontranscribed M-G
      intergenic dinucleotide or within the transcription start sequence of the
      downstream G gene. Immunofluorescence microscopy and immunoprecipitation analysis
      of the mutated minigenomes indicated that the first three nucleotides of the
      transcriptional start sequence are the most critical for efficient VSV gene
      expression, whereas the nontranscribed, intergenic dinucleotide and the other
      conserved nucleotides found at the 5' mRNA start sequence can tolerate
      significant sequence variability without affecting G protein production. RNA
      analysis indicated that nucleotide changes in the transcriptional start sequence
      which resulted in reduced G protein expression correlated with the amount of
      transcript present. Therefore, this conserved sequence appears to be required for
      efficient transcript initiation following polyadenylation of the upstream mRNA.
      While the minimum sequence for efficient transcription (3'-UYGnn-5') is similar
      to that of other rhabdoviruses, it is not homologous to the start sites for
      viruses from the Paramyxoviridae or Filoviridae families. Using Northern blot
      analysis, we also found that some nucleotide changes in the nontranscribed
      intergenic region resulted in higher levels of read-through transcription.
      Therefore, the nontranscribed intergenic dinucleotide plays a role in transcript
      termination.

PMID- 9032347
TI  - Segment-specific noncoding sequences of the influenza virus genome RNA are
      involved in the specific competition between defective interfering RNA and its
      progenitor RNA segment at the virion assembly step.
AB  - The generation of influenza A virus defective interfering (DI) particles was
      studied by using an NS2 mutant which produces, in a single cycle of virus
      replication, a large amount of DI particles lacking the PA polymerase gene. The
      decrease in PA gene replication has been shown to occur primarily at the cRNA
      synthesis step, with preferential amplification of PA DI RNA species present in a
      marginal amount in the virus stock. In addition, at the assembly step the PA DI
      RNAs were preferentially incorporated into virions, resulting in selective
      reduction in the packaging of the PA gene into virions. Similarly, in cells
      dually infected with the NS2 mutant and wild-type viruses, packaging of the wild
      type PA gene was also greatly suppressed. In contrast, incorporation of other RNA
      segments, i.e., the PB2 and NS genes, was not affected, suggesting that the PA DI
      RNAs competed only with the PA gene in a segment-specific manner. Experiments
      involving rescue of recombinant chloramphenicol acetyltransferase (CAT) RNA
      flanked by the noncoding regions of the PA (PA/CAT RNA) and PB2 (PB2/CAT RNA)
      genes into viral particles showed that only PA/CAT RNA was not rescued by
      infection with the NS2 mutant virus containing the PA DI RNAs. However,
      recombinant PA/CAT RNA in which either the 3' or 5' noncoding region was replaced
      with that of the PB2 gene was rescued by the NS2 mutant. These results suggest
      that the noncoding regions of the PA gene are responsible for the competition
      with PA DI RNA species at the virus assembly step and that coexistence of the
      both noncoding regions would be a prerequisite for this phenomenon. Decreased
      packaging of the progenitor RNA by the DI RNA, in addition to the suppression of
      cRNA synthesis, is likely involved in the production of DI particles.

PMID- 9032349
TI  - In vitro selection of packaging sites in a double-stranded RNA virus.
AB  - The Saccharomyces cerevisiae double-stranded RNA virus ScVL1 recognizes a small
      sequence in the viral plus strand for both packaging and replication. Viral
      particles will bind to this viral binding sequence (VBS) with high affinity in
      vitro. An in vitro selection procedure has been used to optimize binding, and the
      sequences isolated have been analyzed for packaging and replication in vivo. The
      selected sequence consists of a stem with a bulged A residue topped by a loop of
      several bases. Four residues of the 18 bases are absolutely conserved for tight
      binding. These all fall in regions that appear to be single stranded. Eight more
      residues have preferred identities, and six of these are in the stem. The VBS is
      similar to the R17 bacteriophage coat protein binding site. Packaging and
      replication require tight binding to viral particles.

PMID- 9032348
TI  - Two Microplitis demolitor polydnavirus mRNAs expressed in hemocytes of
      Pseudoplusia includens contain a common cysteine-rich domain.
AB  - Microplitis demolitor is a polydnavirus-carrying wasp that parasitizes the larval
      stage of Pseudoplusia includens. A previous study indicated that M. demolitor
      polydnavirus (MdPDV) infects primarily hemocytes in parasitized hosts.
      Thereafter, several alterations that compromise the immune response of P.
      includens toward the developing parasitoid occur in hemocytes. In this study, we
      identified two MdPDV mRNAs (1.0 and 1.5 kb) expressed in P. includens hemocytes
      that have homology to the viral genomic clone pMd-2. Corresponding 1.0- and 1.5
      kb cDNA clones (MdPi455 and MdPi59) were isolated from an MdPDV-infected hemocyte
      cDNA library. Nucleotide sequence analysis of the cDNA clones confirmed that the
      1.5- and 1.0-kb mRNAs have significant regions of homology. Sequence alignment
      revealed that the gene, OMd1.0, encoding the 1.0-kb mRNA is present in pMd-2.
      This gene contains two introns and three exons that agree with the sequence for
      MdPi455. In contrast, the 1.5-kb mRNA is likely encoded by a related gene located
      on the same MdPDV genomic DNA as is OMd1.0. The predicted peptide sequences for
      the 1.0- and 1.5-kb transcripts contain a cysteine-rich region at their 5' ends
      that have some similarity with epidermal growth factor-like motifs. Hybridization
      studies revealed that both mRNAs are expressed in granular cells and
      plasmatocytes, the primary classes of hemocytes involved in defense against M.
      demolitor and other parasites.

PMID- 9032350
TI  - Site-directed and linker insertion mutagenesis of herpes simplex virus type 1
      glycoprotein H.
AB  - The gH-gL complex of herpes simplex virus type 1 (HSV-1) is essential for virion
      infectivity and virus-induced cell fusion, but functional domains of the gH
      molecule remain to be defined. We have addressed this question by mutagenesis. A
      set of linker insertion mutants in HSV-1 gH was generated and tested in transient
      assays for their ability to complement a gH-negative virus. Insertions at three
      sites in the C-terminal third of the external domain affected the ability of gH
      to function in cell-cell fusion and virus entry, while insertions at six sites in
      the N-terminal half of the external domain induced conformational changes in gH
      such that it was not recognized by monoclonal antibody LP11, although expression
      at the cell surface was unchanged. A recombinant virus in which a potential
      integrin-binding motif, RGD, in gH was changed to the triplet RGE entered cells
      as efficiently as the wild type, indicating that HSV-1 entry is not mediated by
      means of the gH-RGD motif binding to cell surface integrins. Furthermore,
      mutagenesis of the glycosylation site which is positionally conserved in all
      herpesvirus gH sequences in close proximity to the transmembrane domain generated
      a recombinant virus that grew in vitro with wild-type single-step kinetics.

PMID- 9032351
TI  - Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor
      homolog, mediate extracellular TNF binding and intracellular apoptosis
      inhibition.
AB  - The myxoma virus tumor necrosis factor (TNF) receptor homolog, M-T2, is expressed
      both as a secreted glycoprotein that inhibits the cytolytic activity of rabbit
      TNF-alpha and as an endoglycosidase H-sensitive intracellular species that
      prevents myxoma virus-infected CD4+ T lymphocytes from undergoing apoptosis. To
      compare the domains of M-T2 mediating extracellular TNF inhibition and
      intracellular apoptosis inhibition, recombinant myxoma viruses expressing nested
      C-terminal truncations of M-T2 protein were constructed. One mutant, deltaL113,
      containing intact copies of only two cysteine-rich domains, was not secreted and
      was incapable of binding rabbit TNF-alpha yet retained full ability to inhibit
      virus-induced apoptosis of RL-5 cells. Thus, the minimal domain of intracellular
      M-T2 protein required to inhibit apoptosis is distinct from that required by the
      extracellular M-T2 for functional TNF-alpha binding and inhibition. This is the
      first report of a virus-encoded immunomodular protein with two distinct
      antiimmune properties.

PMID- 9032352
TI  - Characterization of an ATPase activity in reovirus cores and its genetic
      association with core-shell protein lambda1.
AB  - A previously identified nucleoside triphosphatase activity in mammalian reovirus
      cores was further characterized by comparing two reovirus strains whose cores
      differ in their efficiencies of ATP hydrolysis. In assays using a panel of
      reassortant viruses derived from these strains, the difference in ATPase activity
      at standard conditions was genetically associated with viral genome segment L3,
      encoding protein lambda1, a major constituent of the core shell that possesses
      sequence motifs characteristic of other ATPases. The ATPase activity of cores was
      affected by several other reaction components, including temperature, pH, nature
      and concentration of monovalent and divalent cations, and nature and
      concentration of anions. A strain difference in the response of core ATPase
      activity to monovalent acetate salts was also mapped to L3/lambda1 by using
      reassortant viruses. Experiments with different nucleoside triphosphates
      demonstrated that ATP is the preferred ribonucleotide substrate for cores of both
      strains. Other experiments suggested that the ATPase is latent in reovirus
      virions and infectious subviral particles but undergoes activation during
      production of cores in close association with the protease-mediated degradation
      of outer-capsid protein mu1 and its cleavage products, suggesting that mu1 may
      play a role in regulating the ATPase.

PMID- 9032353
TI  - The hepatitis B virus core and e antigens elicit different Th cell subsets:
      antigen structure can affect Th cell phenotype.
AB  - Secretion of the hepatitis B virus (HBV) e antigen (HBeAg) has been conserved
      throughout the evolution of hepadnaviruses. However, the function of this
      secreted form of the viral nucleoprotein remains enigmatic. It has been suggested
      that HBeAg functions as an immunomodulator. We therefore examined the possibility
      that the two structural forms of the viral nucleoprotein, the particulate HBV
      core (HBcAg) and the nonparticulate HBeAg, may preferentially elicit different T
      helper (Th) cell subsets. For this purpose, mice were immunized with recombinant
      HBcAg and HBeAg in the presence and absence of adjuvants, and the immunoglobulin
      G (IgG) isotype profiles of anti-HBc and anti-HBe antibodies were determined.
      Second, in vitro cytokine production by HBcAg- and HBeAg-primed Th cells was
      measured. The immunogenicity of HBcAg, in contrast to that of HBeAg, did not
      require the use of adjuvants. Furthermore, HBcAg elicited primarily IgG2a and
      IgG2b anti-HBc antibodies, with a low level of IgG3, and no IgG1 anti-HBc
      antibodies. In contrast, the anti-HBe antibody response was dominated by the IgG1
      isotype; low levels of IgG2a or IgG2b anti-HBe antibodies and no IgG3 anti-HBe
      antibodies were produced. Cytokine production by HBcAg- and HBeAg-primed Th cells
      was consistent with the IgG isotype profiles. HBcAg-primed Th cells efficiently
      produced interleukin-2 (IL-2) and gamma interferon (IFN-gamma) and low levels of
      IL-4. Conversely, efficient IL-4 production and lesser amounts of IFN-gamma were
      elicited by HBeAg immunization. The results indicate that HBcAg preferentially,
      but not exclusively, elicits Th1-like cells and that HBeAg preferentially, but
      not exclusively, elicits Th0 or Th2-like cells. Because HBcAg and the HBeAg are
      cross-reactive in terms of Th cell recognition, these findings demonstrate that
      Th cells with the same specificity can develop into different Th subsets based on
      the structural form of the immunogen. These results may have relevance to chronic
      HBV infection. Circulating HBeAg may downregulate antiviral clearance mechanisms
      by virtue of eliciting anti-inflammatory Th2-like cytokine production. Last, the
      influence of antigen structure on Th cell phenotype was not absolute and could be
      modulated by in vivo cytokine treatment. For example, IFN-alpha treatment
      inhibited HBeAg-specific Th2-mediated antibody production and altered the IgG
      anti-HBe isotype profile toward the Th1 phenotype.

PMID- 9032354
TI  - Disassociation between the in vitro and in vivo effects of nitric oxide on a
      neurotropic murine coronavirus.
AB  - Intranasal inoculation of the neuroattenuated OBLV60 strain of mouse hepatitis
      virus results in infection of mitral neurons in the olfactory bulb, followed by
      spread along olfactory and limbic pathways to the brain. Immunocompetent BALB/c
      mice were able to clear virus by 11 days postinfection (p.i.). Gamma interferon
      (IFN-gamma) may play a role in clearance of OBLV60 from infected immunocompetent
      BALB/c mice through a nonlytic mechanism. Among the variety of immunomodulatory
      activities of IFN-gamma is the induction of expression of inducible nitric oxide
      synthase (iNOS), an enzyme responsible for the production of nitric oxide (NO).
      Studies were undertaken to investigate the role of IFN-gamma and NO in host
      defense and clearance of OBLV60 from the central nervous system (CNS). Exposure
      of OBLV60-infected OBL21a cells, a mouse neuronal cell line, to the NO-generating
      compound S-nitroso-L-acetyl penicillamine resulted in a significant decrease in
      viral replication, indicating that NO interfered with viral replication.
      Furthermore, infection of IFN-gamma knockout (GKO) mice and athymic nude mice
      with OBLV60 resulted in low-level expression of iNOS mRNA and protein in the
      brains compared to that of OBLV60-infected BALB/c mice. Nude mice were unable to
      clear virus and eventually died between days 11 and 14 p.i. (B. D. Pearce, M. V.
      Hobbs, T. S. McGraw, and M. J. Buchmeier, J. Virol. 68:5483-5495, 1994); however,
      GKO mice survived infection and cleared virus by day 18 p.i. These data suggest
      that IFN-gamma production in the olfactory bulb contributed to but may not be
      essential for clearance of OBLV60 from the brain. In addition, treatment of
      OBLV60-infected BALB/c mice with aminoguanidine, a selective inhibitor of iNOS
      activity, did not result in any increase in mortality, and the mice cleared the
      virus by 11 days p.i. These data suggest that although NO was able to block
      replication of virus in vitro, expression of iNOS with NO release in vivo did not
      appear to be the determinant factor in clearance of OBLV60 from CNS neurons.

PMID- 9032355
TI  - Two proline residues are essential in the calcium-binding activity of rotavirus
      VP7 outer capsid protein.
AB  - Rotavirus maturation and stability of the outer capsid are calcium-dependent
      processes. It has been shown previously that the concentration of Ca2+
      solubilizing outer capsid proteins from rotavirus particles is dependent on the
      virus strain. This property of viral particles has been associated with the gene
      coding for VP7 (gene 9). In this study the correlation between VP7 and resistance
      to low [Ca2+] was confirmed by analyzing the origin of gene 9 from reassortant
      viruses prepared under the selective pressure of low [Ca2+]. After chemical
      mutagenesis, we selected mutant viruses of the bovine strain RF that are more
      resistant to low [Ca2+]. The genes coding for the VP7 proteins of these
      independent mutants have been sequenced. Sequence analysis confirmed that these
      mutants are independent and revealed that all mutant VP7 proteins have proline 75
      changed to leucine and have an outer capsid that solubilized at low [Ca2+]. The
      mutation of proline 279 to serine is found in all but two mutants. The phenotype
      of mutants having a single proline change can be distinguished from the phenotype
      of mutants having two proline changes. Sequence analysis showed that position 75
      is in a region (amino acids 65 to 78) of great variability and that proline 75 is
      present in most of the bovine strains. In contrast, proline 279 is in a conserved
      region and is conserved in all the VP7 sequences in data banks. This region is
      rich in oxygenated residues that are correctly allocated in the metal
      coordinating positions of the Ca2+-binding EF-hand structure pattern, suggesting
      that this region is important in the Ca2+ binding of VP7.

PMID- 9032356
TI  - Induction of cyclins E and A in response to mitogen removal: a basic alteration
      associated with the arrest of differentiation of C2 myoblasts transformed by
      simian virus 40 large T antigen.
AB  - We previously showed that C2 myoblasts transformed by simian virus 40 large T
      antigen (SVLT) stop the myogenic process after the induction of myogenin and of
      high Rb levels; the induced Rb, however, becomes notably phosphorylated. We have
      analyzed the protein levels and activities of cyclin-dependent kinases (cdks) in
      untransformed C2 cells and in transformants of either SVLT or the cytoplasmic
      mutant NKT1 (which permits differentiation) upon a shift from growth medium (GM)
      to mitogen-poor differentiation medium (DM). After the shift, cdk4 levels
      remained constant and cdk6 levels decreased in all cell types; cdk2 minimally
      increased only in SVLT cells. Cyclin D1 was downregulated in DM in all cell
      types, and cyclin D3 was upregulated (albeit less strongly in SVLT cells than in
      the others). In contrast, a dramatic difference between SVLT cells and the other
      cells was observed for cyclins E and A, which essentially disappeared (as protein
      and RNA) in normal C2 and NKT1 cells upon the shift from GM to DM, whereas they
      increased in SVLT cells. Concurrently, cdk2 activity ceased in C2 and NKT1 cells
      in DM, whereas it persisted at 20% of the GM level in SVLT cells. cdk4 activity
      was detectable in all cells only in GM. Cyclin E and A induction thus appeared to
      sustain enough Rb phosphorylation to interfere with tissue-specific expression,
      with cdk activity not high enough to activate cyclin self-regulation. In DM, cdk2
      complexed to D3 was underphosphorylated in all cells, and SVLT allowed strong
      inductions of p21 and p27 without affecting their complexes with cdks.

PMID- 9032358
TI  - Accumulation of defective viral genomes in peripheral blood mononuclear cells of
      human immunodeficiency virus type 1-infected individuals.
AB  - Human immunodeficiency virus type 1 (HIV-1) genomes present in peripheral blood
      mononuclear cells (PBMCs) of infected persons or in lymphocytes infected in vitro
      were studied by long-distance PCR (LD-PCR) using primers localized in the HIV-1
      long terminal repeats. The full-length 9-kb DNA was the only LD-PCR product
      obtained in peripheral and cord blood lymphocytes from seronegative donors
      infected in vitro. However, a high proportion (27% to 66%) of distinct
      populations of extensively deleted HIV-1 genomes of variable size was detected in
      PBMCs of 15 of 16 HIV-1-infected persons. Physical mapping of defective genomes
      showed that the frequency of deletions is proportional to their proximity to the
      central part of HIV-1 genome, which is consistent with a deletion mechanism
      involving a single polymerase jump during reverse transcription. Sequencing of
      deletion junctions revealed the presence of short direct repeats of three or four
      nucleotides. The number of defective HIV-1 genomes decreased after in vitro
      activation of PBMCs. Persistence of full-length and deleted genomes in in vitro
      activated PBMCs correlated with isolation of an infectious virus. Our results
      represent the first quantitative assessment of intragenomic rearrangements in HIV
      1 genomes in PBMCs of infected persons and demonstrate that, in contrast to in
      vitro infection, defective genomes accumulate in PBMCs of infected persons.

PMID- 9032357
TI  - Construction, replication, and immunogenic properties of a simian
      immunodeficiency virus expressing interleukin-2.
AB  - To study the effect of interleukin-2 (IL-2) on simian immunodeficiency virus
      (SIV) replication, pathogenesis, and immunogenicity, we replaced the nef gene of
      SIVmac239 by the IL-2 coding region. The virus, designated SIV-IL2, stably
      expressed high levels of IL-2 in cell culture. In comparison to SIVmac239, SIV
      IL2 replicated more efficiently in peripheral blood mononuclear cells in the
      absence of exogenously added IL-2. To determine whether this growth advantage
      would be of relevance in vivo, four juvenile rhesus monkeys were infected with
      SIV-IL2 and four monkeys were infected with a nef deletion mutant of SIV
      (SIVdeltaNU). After a peak in the cell-associated viral load 2 weeks
      postinfection, the viruses could barely be isolated 3 to 7 months postinfection.
      Mean capsid antigen levels were higher in the SIV-IL2 group than in the nef
      deletion group 2 weeks postinfection. Viruses reisolated from the SIV-IL2
      infected animals expressed high levels of IL-2 during the acute phase of
      infection. Deletions in the IL-2 coding region of SIV-IL2 were observed in two of
      the SIV-IL2-infected macaques 3 months postinfection. Urinary neopterin levels, a
      marker for unspecific immune stimulation, were higher in the SIV-IL2-infected
      macaques than in SIVdeltaNU-infected animals during the acute phase of infection.
      The SIV-specific T-cell-proliferative response and antibody titers were similar
      in both groups. Cytotoxic T cells directed against viral antigens were detected
      in all SIV-IL2-infected macaques and in two of the SIVdeltaNU-infected animals.
      Expression of IL-2 did not seem to alter the attenuated phenotype of nef deletion
      mutants fundamentally, although there might have been a slight increase in virus
      replication and immune stimulation during the acute phase of infection. Deletion
      of the viral IL-2 gene 3 months postinfection could be a consequence of a
      selective disadvantage due to local coexpression of viral antigen and IL-2 in the
      presence of an antiviral immune response.

PMID- 9032361
TI  - Characterization of an RNA-dependent RNA polymerase activity associated with La
      France isometric virus.
AB  - Purified preparations of La France isometric virus (LIV), an unclassified, double
      stranded RNA (dsRNA) virus of Agaricus bisporus, were associated with an RNA
      dependent RNA polymerase (RDRP) activity. RDRP activity cosedimented with the 36
      nm isometric particles and genomic dsRNAs of LIV during rate-zonal centrifugation
      in sucrose density gradients, suggesting that the enzyme is a constituent of the
      virion. Enzyme activity was maximal in the presence of all four nucleotides, a
      reducing agent (dithiothreitol or beta-mercaptoethanol), and Mg2+ and was
      resistant to inhibitors of DNA-dependent RNA polymerases (actinomycin D, alpha
      amanitin, and rifampin). The radiolabeled enzyme reaction products were
      predominantly (95%) single-stranded RNA (ssRNA) as determined by cellulose column
      chromatography and ionic-strength-dependent sensitivity to hydrolysis by RNase A.
      Three major size classes of ssRNA transcripts of 0.95, 1.3, and 1.8 kb were
      detected by agarose gel electrophoresis, although the transcripts hybridized to
      all nine of the virion-associated dsRNAs. The RNA products synthesized in vitro
      appeared to be of a single polarity, as they hybridized to an ssDNA corresponding
      to one strand of a genomic dsRNA and not to the complementary strand. Similarly,
      reverse transcription-PCR with total cellular ssRNA as a template and strand
      specific primers targeting a genomic dsRNA during synthesis of cDNA suggested
      that only the coding strand was transcribed in vivo. Our data indicate that the
      RDRP activity associated with virions of LIV is probably a transcriptase engaged
      in the synthesis of ssRNA transcripts corresponding to each of the virion
      associated dsRNAs.

PMID- 9032360
TI  - Functional phenotype of transformed human alphabeta and gammadelta T cells
      determined by different subgroup C strains of herpesvirus Saimiri.
AB  - Based on sequence divergence in the transformation-relevant region, herpesvirus
      saimiri strains are classified into three subgroups. Only members of subgroup C
      transform human T lymphocytes to continuous interleukin-2-dependent growth in
      culture. In this study, human cord blood T cells were immortalized by using
      different subgroup C strains (C488, C484, and C139). The resulting T-cell lines
      represented different types of T-cell clones. They were either CD4+ or CD8+ and
      expressed either the alphabeta or the gammadelta type of T-cell receptors. If
      transformed by the same virus strain, alphabeta and gammadelta clones were
      similar with respect to viral persistence, virus gene expression, proliferation,
      and Th1-type cytokine production. However, major differences were observed in T
      cells immortalized by different subgroup C strains. Strain C139 persisted at low
      copy number, compared to the high copy number of prototype C488. The
      transformation-associated genes stpC and tip of strain C488 were strongly induced
      after T-cell stimulation. The homologous genes of strain C139 were only weakly
      expressed and not induced after activation. After CD2 ligation, the C488
      transformed T cells produced interleukin-2, whereas the C139-transformed cells
      did not. Correspondingly, the C139-transformed T cells were less sensitive to
      cyclosporin A. Sequence comparison from different subgroup C strains revealed a
      variability of the stpC/tip promoter region and of the Lck-binding viral protein
      Tip. Thus, closely related subgroup C strains of herpesvirus saimiri cause major
      differences in the functional phenotype of growth-transformed human T cells.

PMID- 9032359
TI  - Human CD4+ T-cell response to hepatitis delta virus: identification of multiple
      epitopes and characterization of T-helper cytokine profiles.
AB  - The T-cell-mediated immune response plays a crucial role in defense against
      hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides.
      However, very little is known about the role of specific T cells during hepatitis
      delta virus (HDV) infection in humans. In this study, the T-cell response to HDV
      in chronic hepatitis B virus (HBV) carriers with HDV superinfection was
      investigated at different levels. Analysis of peripheral blood mononuclear cell
      (PBMC) proliferation in response to a recombinant form of large hepatitis delta
      antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically
      responded to HDAg. By employing synthetic peptides spanning the entire HDAg
      sequence, we found that T-cell recognition was directed against different
      antigenic determinants, with patient-to-patient variation in the pattern of
      response to peptides. Interestingly, all responders had signs of inactive HDV
      induced disease, while none of the patients with active disease and none of the
      control subjects showed any significant proliferation. More accurate information
      about the specific T-cell response was obtained at the clonal level. A panel of
      HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine
      specificity analysis revealed that the clones tested individually recognized four
      epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106
      to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction
      revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells
      in association with multiple class II molecules. In addition, peptide 26 to 41
      was efficiently generated after processing of HDAg through the endogenous
      processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell
      clones assayed were able to produce high levels of gamma interferon (IFN-gamma),
      belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were
      cytotoxic in a specific assay. This study provides the first evidence that
      detection of a specific T-cell response to HDAg in the peripheral blood of
      individuals with hepatitis delta is related to the decrease of HDV-induced
      disease activity. The HDAg epitopes identified here and particularly those
      recognized by CD4+ T cells in association with multiple major histocompatibility
      complex class II molecules may be potentially exploited for the preparation of a
      vaccine for prophylaxis and therapy of HDV infection.

PMID- 9032362
TI  - Deletion of the C-terminal 33 amino acids of cucumber mosaic virus movement
      protein enables a chimeric brome mosaic virus to move from cell to cell.
AB  - The movement protein (MP) gene of brome mosaic virus (BMV) was precisely replaced
      with that of cucumber mosaic virus (CMV). Infectivity tests of the chimeric BMV
      on Chenopodium quinoa, a permissive host for cell-to-cell movement of both BMV
      and CMV, showed that the chimeric BMV failed to move from cell to cell even
      though it replicated in protoplasts. A spontaneous mutant of the chimeric BMV
      that displayed cell-to-cell movement was subsequently obtained from a local
      lesion during one of the experiments. A cloned cDNA representing the genomic RNA
      encoding the MP of the chimeric BMV mutant was analyzed and found to contain a
      mutation in the CMV MP gene resulting in deletion of the C-terminal 33 amino
      acids of the MP. Directed mutagenesis of the CMV MP gene showed that the C
      terminal deletion was responsible for the movement capability of the mutant. When
      the mutation was introduced into CMV, the CMV mutant moved from cell to cell in
      C. quinoa, though the movement was less efficient than that of the wild-type CMV.
      These results indicate that the CMV MP, except the C-terminal 33 amino acids,
      potentiates cell-to-cell movement of both BMV and CMV in C. quinoa. In addition,
      since C. quinoa is a common host for both BMV and CMV, these results suggest that
      the CMV MP has specificity for the viral genomes during cell-to-cell movement of
      the virus and that the C-terminal 33 amino acids of the CMV MP are involved in
      that specificity.

PMID- 9032364
TI  - Glycoprotein H of herpes simplex virus type 1 requires glycoprotein L for
      transport to the surfaces of insect cells.
AB  - In mammalian cells, formation of heterooligomers consisting of the glycoproteins
      H and L (gH and gL) of herpes simplex virus type 1 is essential for the cell-to
      cell spread of virions and for the penetration of virions into cells. We examined
      whether formation of gH1/gL1 heterooligomers and cell surface expression of the
      complex occurs in insect cells. Three recombinant baculoviruses, expressing gL1,
      gH1, and truncated gH1 (gH1t), which lacks the transmembrane region, were
      constructed. It was shown that recombinant gH1/gL1 and gH1t/gL1 heterooligomers
      were produced in insect cells. As in mammalian cells, gH1 and gH1t were not
      detected on the surfaces of insect cells in the absence of gL1. When coexpressed
      with gL1, recombinant gH1 was displayed on the surfaces of insect cells.
      Coexpression of gH1t and gL1 resulted in secretion of the gH1t/gL1 complex into
      the cell culture medium, indicating that gH1t is also transported to the surfaces
      of insect cells. Our results indicate that the process of folding and
      intracellular transport of gH1 and gL1 is comparable in insect cells and
      mammalian cells and that the baculovirus expression system can be used to examine
      the complex formation and the intracellular transport of gH1 and gL1. The
      availability of secreted gH1t/gL1 complex offers the opportunity to further
      investigate the immunological properties of this complex.

PMID- 9032365
TI  - A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th
      epitopes from several microbes, induces appropriate responses in vivo and confers
      protection against more than one pathogen.
AB  - The development of safe and effective vaccines remains a major goal in the
      prevention, and perhaps treatment, of infectious diseases. Ideally, a single
      vaccine would confer protection against several pathogens and would induce both
      cellular and humoral arms of the immune response. We originally demonstrated that
      two virus-specific cytotoxic T-lymphocyte (CTL) epitopes, from the same virus but
      presented by different major histocompatibility complex alleles, when linked in
      tandem as minigenes in a recombinant vaccinia virus, could confer complete
      protection against subsequent viral challenge. In the study, we extended this
      approach, which we termed string of beads, expanding the immunogenic scope in two
      ways: first, by introduction of T helper (Th) and B-cell (antibody) epitopes
      alongside CTL epitopes and second, by including immunogenic sequences from a
      variety of infectious agents, five viruses and one bacterium. The vaccine (VV-sv)
      comprises CTL epitopes from Sendai virus, respiratory syncytial virus, and
      lymphocytic choriomeningitis virus (LCMV); Th epitopes from vesicular stomatitis
      virus and Mycobacterium tuberculosis; and an antibody epitope from mengovirus.
      The construct contains a single start codon, and the epitopes are linked
      directly, without intervening spacer amino acids. There was some concern that the
      combination of several normally immunodominant epitopes might result in a new
      hierarchy of dominance, in which certain epitopes predominated and others
      exhibited reduced immunogenicity. However we show that when analyzed in tissue
      culture and in vivo, all six epitopes are expressed. CTL and Th cells are induced
      in vivo, along with neutralizing antibody. The induced immunity is biologically
      relevant: after VV-sv immunization, the antimengovirus antibody confers
      protection against mengovirus challenge. Similarly, CTL induced by the LCMV
      epitope protected mice against challenge with this agent. Thus, a polyvalent,
      minigene-based vaccine can simultaneously induce several classes of immune
      response and thereby can confer protection against diverse pathogens.

PMID- 9032363
TI  - Generation of cytotoxic T lymphocytes against immunorecessive epitopes after
      multiple immunizations with adenovirus vectors is dependent on haplotype.
AB  - Currently, adenovirus (Ad) is being considered as a vector for the treatment of
      cystic fibrosis as well as other diseases. However, the cytotoxic T lymphocyte
      (CTL) response to Ad could limit the effectiveness of such approaches. Since the
      CTL response to virus infection is often focused on one or a few immunodominant
      epitopes, one approach to circumvent this response is to create vectors that lack
      these immunodominant epitopes. The effectiveness of this approach was tested by
      immunizing mice with human group C adenoviruses. Three mouse strains (C57BL/10SnJ
      [H-2b], C3HeB/FeJ [H-2k], and BALB/cByJ [H-2d]) were immunized with wild-type Ad
      or Ad vectors lacking the immunodominant antigen(s), and the CTL responses were
      measured. In C57BL/10 (B10) mice, a single inoculation intraperitoneally (i.p.)
      led to the recognition of an immunodominant antigen in E1A. When B10 mice were
      inoculated multiple times either i.p. or intranasally with wild-type Ad or an Ad
      vector lacking most of the E1 region, subdominant epitopes outside this region
      were recognized. In contrast, C3H mice inoculated with wild-type Ad recognized an
      epitope mapping within E1B. When inoculated twice with Ad vectors lacking both
      E1A and E1B, no immunorecessive epitopes were recognized. The immune response to
      Ad in BALB/c mice was more complex. CTLs from BALB/c mice inoculated i.p. with
      wild-type Ad recognized E1B in the context of the major histocompatibility
      complex (MHC) class I Dd allele and a region outside E1 associated with the Kd
      allele. When BALB/c mice were inoculated with E1-deleted Ad vectors, only the
      immunodominant Kd-restricted epitope was recognized, and Dd-restricted CTLs did
      not develop. This report indicates that the emergence of CTLs against
      immunorecessive epitopes following multiple administrations of Ad vectors lacking
      immunodominant antigens is dependent on haplotype and could present an obstacle
      to gene therapy in an MHC-diverse human population.

PMID- 9032366
TI  - Oral immunization with recombinant Mycobacterium bovis BCG simian
      immunodeficiency virus nef induces local and systemic cytotoxic T-lymphocyte
      responses in mice.
AB  - Recombinant live Mycobacterium bovis BCG vectors (rBCG) induce strong cellular
      and humoral immune responses against various antigens after either systemic or
      oral immunization of mice. Cytotoxic T-lymphocyte (CTL) responses may contribute
      to the control of human immunodeficiency virus (HIV) or simian immunodeficiency
      virus (SIV) infections whose portal of entry is the gastrointestinal or genital
      mucosa. In this study, we immunized BALB/c mice with a recombinant BCG SIV nef
      and observed its behavior in oropharyngeal and target organ lymphoid tissues. The
      cellular immune responses, particularly the intestinal intraepithelial and
      systemic CTL responses, were investigated. The results showed that rBCG SIV nef
      translocated the oropharyngeal mucosa and intestinal epithelium. It diffused to
      and persisted in target lymphoid organs. Specific SIV Nef peptide proliferative
      responses and cytokine production were observed. Strong systemic and mucosal CTL
      responses were induced. In particular, we demonstrated direct specific anti-Nef
      CTL in intestinal intraepithelial CD8beta+ T cells. These findings provide
      evidence that orally administered rBCG SIV nef may contribute to local defenses
      against viral invasion. Therefore, rBCG SIV nef could be a candidate vaccine to
      protect against SIV infection and may be used to develop an oral rBCG HIV nef
      vaccine.

PMID- 9032367
TI  - In vitro genetic selection analysis of alfalfa mosaic virus coat protein binding
      to 3'-terminal AUGC repeats in the viral RNAs.
AB  - The coat proteins of alfalfa mosaic virus (AMV) and the related ilarviruses bind
      specifically to the 3' untranslated regions of the viral RNAs, which contain
      conserved repeats of the tetranucleotide sequence AUGC. The purpose of this study
      was to develop a more detailed understanding of RNA sequence and/or structural
      determinants required for coat protein binding by characterizing the role of the
      AUGC repeats. Starting with a complex pool of 39-nucleotide RNA molecules
      containing random substitutions in the AUGC repeats, in vitro genetic selection
      was used to identify RNAs that bound coat protein. After six iterative rounds of
      selection, amplification, and reselection, 25% of the RNAs selected from the
      randomized pool were wild type; that is, they contained all four AUGC sequences.
      Among the 31 clones analyzed, AUGC was clearly the preferred selected sequence at
      the four repeats, but some nucleotide sequence variability was observed at
      AUGC(865-868) if the other three AUGC repeats were present. Variant RNAs that
      bound coat protein with affinities equal to or greater than that of the wild-type
      molecule were not selected. To extend the in vitro selection results, RNAs
      containing specific nucleotide substitutions were transcribed in vitro and tested
      in coat protein and peptide binding assays. The data strongly suggest that the
      AUGC repeats provide sequence-specific determinants and contribute to a
      structural platform for specific coat protein binding. Coat protein may function
      in maintaining the 3' ends of the genomic RNAs during replication by stabilizing
      an RNA structure that defines the 3' terminus as the initiation site for minus
      strand synthesis.

PMID- 9032369
TI  - Assembly of African swine fever virus: role of polyprotein pp220.
AB  - Polyprotein processing is a common strategy of gene expression in many positive
      strand RNA viruses and retroviruses but not in DNA viruses. African swine fever
      virus (ASFV) is an exception because it encodes a polyprotein, named pp220, to
      produce several major components of the virus particle, proteins p150, p37, p34,
      and p14. In this study, we analyzed the assembly pathway of ASFV and the
      contribution of the polyprotein products to the virus structure. Electron
      microscopic studies revealed that virions assemble from membranous structures
      present in the viral factories. Viral membranes became polyhedral immature
      virions after capsid formation on their convex surface. Beneath the lipid
      envelope, two distinct domains appeared to assemble consecutively: first a thick
      protein layer that we refer to as core shell and then an electron-dense nucleoid,
      which was identified as the DNA-containing domain. Immunofluorescence studies
      showed that polyprotein pp220 is localized in the viral factories. At the
      electron microscopic level, antibodies to pp220 labeled all identifiable forms of
      the virus from the precursor viral membranes onward, thus indicating an early
      role of the polyprotein pp220 in ASFV assembly. The subviral localization of the
      polyprotein products, examined on purified virions, was found to be the core
      shell. In addition, quantitative studies showed that the polyprotein products are
      present in equimolar amounts in the virus particle and account for about one
      fourth of its total protein content. Taken together, these results suggest that
      polyprotein pp220 may function as an internal protein scaffold which would
      mediate the interaction between the nucleoid and the outer layers similarly to
      the matrix proteins of other viruses.

PMID- 9032368
TI  - Study of the dynamics of neutralization escape mutants in a chimpanzee naturally
      infected with the simian immunodeficiency virus SIVcpz-ant.
AB  - Here we report on the use of spectral map analysis of time-paired sequential
      neutralization data of 11 serum samples of a chimpanzee naturally infected with a
      simian immunodeficiency virus (SIVcpz-ant) and 8 primary consecutive SIVcpz-ant
      isolates, taken at about 4-month intervals. The analysis reveals the existence of
      three SIVcpz-ant isolate and serum neutralization clusters. Each cluster groups
      virus isolates and/or sera based on similarities of their neutralization spectra.
      On average, neutralization escape mutants emerged after 15 months and mounted a
      neutralization response approximately 8 months later. The entire gp160 regions of
      eight consecutive isolates were sequenced and analyzed by a new statistical
      method called polygram, which allowed the deduction of amino acid sequence motifs
      of gp160 which were specific for SIVcpz-ant isolates belonging to the same
      isolate neutralization clusters. Changes in specific amino acid quadruplets in
      V1, V2, C3, V4, V5, and CD4 domains of gp120 and gp40 were seen to correlate with
      the neutralization clusters with most of the specific changes occurring in the V4
      region. This method of analysis may facilitate an understanding of the study of
      the dynamic interplay between human immunodeficiency virus (HIV) and host
      neutralization responses as well as providing possible insights into mechanisms
      of persistence of HIV-1-related lentiviruses in their natural hosts.

PMID- 9032370
TI  - Failure to transmit disease from gray tremor mutant mice.
AB  - Mice homozygous for mutant alleles at the gray tremor (gt) locus develop a marked
      non-intention tremor beginning at 8 days of age. Most homozygous mice die by 3
      months. Homozygotes exhibit intense vacuolation of the central nervous system
      gray matter and vacuolation and hypomyelination of some white matter tracts.
      Based on neuropathological similarities with scrapie, other investigators
      inoculated wild-type mice with gray tremor brain homogenates to test the
      hypothesis of transmissibility. Published reports indicated that spongiform
      encephalopathy (R. L. Sidman, H. C. Kinney, and H. O. Sweet, Proc. Natl. Acad.
      Sci. USA 82:253-257, 1985) and disease, including hind limb paralysis in NFS mice
      (P. M. Hoffman, R. G. Rohwer, C. MacAuley, J. A. Bilello, J. W. Hartley, and H.
      C. Morse III, Proc. Natl. Acad. Sci. USA 84:3866-3870, 1987), were transmitted by
      inoculation of gt/gt brain homogenates. In our hands, however, no NFS/NCr animals
      inoculated intracerebrally with gt/gt or +/+ brain preparations showed any signs
      of disease or pathological changes in the brain. Positive transmission by other
      investigators may reflect the microbiological status of their donor or recipient
      mice.

PMID- 9032371
TI  - A conserved hairpin motif in the R-U5 region of the human immunodeficiency virus
      type 1 RNA genome is essential for replication.
AB  - The untranslated leader region of the human immunodeficiency virus (HIV) RNA
      genome contains multiple hairpin motifs. The repeat region of the leader, which
      is reiterated at the 3' end of the RNA molecule, encodes the well-known TAR
      hairpin and a second hairpin structure with the polyadenylation signal AAUAAA in
      the single-stranded loop [the poly(A) hairpin]. The fact that this poly(A) stem
      loop structure and its thermodynamic stability are well conserved among HIV and
      simian immunodeficiency virus isolates, despite considerable divergence in
      sequence, suggests a biological function for this RNA motif in viral replication.
      Consistent with this idea, we demonstrate that mutations that alter the stability
      of the stem region or delete the upper part of the hairpin do severely inhibit
      replication of HIV type 1. Whereas destabilizing mutations in either the left- or
      right-hand side of the base-paired stem interfere with virus replication, the
      double mutant, which allows the formation of new base pairs, replicates more
      rapidly than the two individual virus mutants. Upon prolonged culturing of
      viruses with an altered hairpin stability, revertant viruses were obtained with
      additional mutations that restore the thermodynamic stability of the poly(A)
      hairpin. Transient transfection experiments demonstrated that transcription of
      the proviral genomes, translation of the viral mRNAs, and reverse transcription
      of the genomic RNAs are not affected by mutation of the 5' poly(A) hairpin. We
      show that the genomic RNA content of the virions is reduced by destabilization of
      this poly(A) hairpin but not by stabilization or truncation of this structure.
      These results suggest that the formation of the poly(A) hairpin structure at the
      5' end of the genomic RNA molecule is necessary for packaging of viral genomes
      into virions and/or stability of the virion RNA.

PMID- 9032373
TI  - An RNA tertiary structure in the 3' untranslated region of enteroviruses is
      necessary for efficient replication.
AB  - RNA tertiary structures, such as pseudoknots, are known to be biologically
      significant in a number of virus systems. The 3' untranslated regions of the RNA
      genomes of all members of the Enterovirus genus of Picornaviridae exhibit a
      potential, pseudoknot-like, tertiary structure interaction of an unusual type.
      This is formed by base pairing between loop regions of two secondary structure
      domains. It is distinct from a potential, conventional pseudoknot, studied
      previously in poliovirus, which is less conserved phylogenetically. We have
      analyzed the tertiary structure feature in one enterovirus, coxsackievirus A9,
      using specific mutagenesis. A double mutant in which the potential interaction
      was destroyed was nonviable, and viability was restored by introducing
      compensating mutations, predicted to allow the interaction to reform. Phenotypic
      pseudorevertants of virus mutants, having mutations designed to disrupt the
      interaction, were all found to have acquired nucleotide changes which restored
      the potential interaction. Analysis of one mutant containing a single-base
      mutation indicated a greatly increased temperature sensitivity due to a step
      early in replication. The results show that, in addition to secondary structures,
      tertiary RNA structural interactions can play an important role in the biology of
      picornaviruses.

PMID- 9032372
TI  - A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from
      feline immunodeficiency virus confers resistance to oxathiolane nucleosides.
AB  - Variants of feline immunodeficiency virus (FIV) that possess a unique methionine
      to-threonine mutation within the YMDD motif of reverse transcriptase (RT) were
      selected by culturing virus in the presence of inhibitory concentrations of (-)
      beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC]. The mutants were
      resistant to (-)-FTC and (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) and
      additionally exhibited low-level resistance to 2',3'-dideoxycytidine (ddC). DNA
      sequence analysis of the RT-encoding region of the pol gene amplified from
      resistant viruses consistently identified a Met-to-Thr mutation in the YMDD
      motif. Purified RT from the mutants was also resistant to the 5'-triphosphate
      forms of 3TC, (-)-FTC, and ddC. Site-directed mutants of FIV were engineered
      which contain either the novel Met-to-Thr mutation or the Met-to-Val mutation
      seen in oxathiolane nucleoside-resistant HIV-1. Both site-directed mutants
      displayed resistance to 3TC, thus confirming the role of these mutations in the
      resistance of FIV to beta-L-3'-thianucleosides.

PMID- 9032374
TI  - Characterization of the components and activity of Sonchus yellow net rhabdovirus
      polymerase.
AB  - Sonchus yellow net virus (SYNV) is the best-characterized member of a group of
      plant rhabdoviruses that replicate in the host cell nucleus. Using a recently
      developed method for partial purification of active SYNV polymerase by salt
      extraction of nuclei from infected plant tissue (J. D. O. Wagner et al, J. Virol.
      70:468-477, 1996), we have identified the nucleocapsid (N), M2, and L proteins as
      polymerase complex components (based on copurification with the polymerase
      activity and by coimmunoprecipitation assays). Furthermore, the L protein was
      shown by antibody inhibition analysis to be a functional component of the
      polymerase. A second complex of M2 and L proteins, thought to be a precursor to
      the polymerase complex, was also identified. In addition, we conducted a detailed
      characterization of SYNV RNA synthesis in vitro. The results demonstrate that the
      RNAs are transcribed sequentially, beginning with the N mRNA and followed
      successively by the remaining five mRNAs in the order of their genome
      organization. Gene expression conforms to a cascade pattern, with synthesis of
      the 3'-proximal N mRNA occurring at the highest level, followed by consecutively
      lower levels of transcription from each subsequent gene. The reaction conditions
      favor transcription over minus-sense RNA replication, which, we posit, is
      inhibited near specific signal sequences located on the antigenomic template. The
      results support the concept that the mechanism of transcription is highly
      conserved among diverse rhabdoviruses and are compatible with a unified model for
      the regulation of genomic and antigenomic RNA synthesis.

PMID- 9032376
TI  - Formation of herpes simplex virus type 1 replication compartments by
      transfection: requirements and localization to nuclear domain 10.
AB  - During infection, the seven essential herpes simplex virus type 1 (HSV-1)
      replication proteins are found in globular nuclear structures called replication
      compartments. Replication compartments form adjacent to ND10, nuclear matrix
      bound domains which are present in most cell types but whose function is unknown
      (G. G. Maul, I. M. Ishov, and R. D. Everett, Virology 217:67-75, 1996). We now
      demonstrate that replication compartments can be formed by cotransfecting Vero
      cells with constructs expressing the seven essential viral replication proteins
      and a plasmid containing an HSV-1 origin of DNA replication. Like replication
      compartments in infected cells, replication compartments formed by cotransfection
      contain all of the essential viral replication proteins, are sites of DNA
      synthesis, and are found adjacent to ND10. However, neither the viral origin
      binding protein nor a plasmid containing an HSV-1 origin of DNA replication is
      individually required for the formation of transfection replication compartments,
      although the presence of each increases the efficiency of replication compartment
      formation. Further, we provide evidence that UL29 independently localizes
      adjacent to ND10 and so may play a role in directing replication compartments to
      these preexisting nuclear structures.

PMID- 9032375
TI  - Mutational analysis of the oligomer assembly domain in the transmembrane subunit
      of the Rous sarcoma virus glycoprotein.
AB  - The transmembrane (TM) subunits of retroviral envelope glycoproteins appear to
      direct the assembly of the glycoprotein precursor into a discrete oligomeric
      structure. We have examined mutant Rous sarcoma virus envelope proteins with
      truncations or deletions within the ectodomain of TM for their ability to
      oligomerize in a functional manner. Envelope proteins containing an intact
      surface (SU) domain and a TM domain truncated after residue 120 or 129 formed
      intracellular trimers in a manner similar to that of proteins that had an intact
      ectodomain and were efficiently secreted. Whereas independent expression of the
      SU domain yielded an efficiently transported molecule, proteins containing SU and
      17, 29, 37, 59, 73, 88, and 105 residues of TM were defective in intracellular
      transport. With the exception of a protein truncated after residue 88 of TM, the
      truncated proteins were also defective in formation of stable trimers that could
      be detected on sucrose gradients. Deletion mutations within the N-terminal 120
      amino acids of TM also disrupted transport to the Golgi complex, but a majority
      of these mutant glycoproteins were still able to assemble trimers. Deletion of
      residues 60 to 74 of TM caused the protein to remain monomeric, while a deletion
      C terminal of residue 88 that removed two cysteine residues resulted in
      nonspecific aggregation. Thus, it appears that amino acids throughout the N
      terminal 120 residues of TM contribute to assembly of a transport-competent
      trimer. This region of TM contains two amino acid domains capable of forming
      alpha helices, separated by a potential disulfide-bonded loop. While the N
      terminal helical sequence, which extends to residue 85 of TM, may be capable of
      mediating the formation of Env trimers if C-terminal sequences are deleted, our
      results show that the putative disulfide-linked loop and C-terminal alpha-helical
      sequence play a key role in directing the formation of a stable trimer that is
      competent for intracellular transport.

PMID- 9032377
TI  - Induction of degenerative brain lesions after adoptive transfer of brain
      lymphocytes from Borna disease virus-infected rats: presence of CD8+ T cells and
      perforin mRNA.
AB  - Lymphocytes were isolated from the brains of Borna disease virus-infected donor
      Lewis rats at various time points after infection. Cell populations were
      characterized by cytofluorometry, with special emphasis on CD4+ and CD8+ cells.
      Testing of isolated lymphocytes revealed major histocompatibility complex class I
      restricted cytotoxic activity. Reverse transcription-PCR analyses of brain
      homogenates of infected donors revealed the presence of CD8 mRNA after day 11 of
      infection and of perforin mRNA between days 13 and 25 after infection. Adoptive
      transfers of lymphocytes isolated from the brain at days 13 and 21 resulted in
      severe neurological symptoms, resembling experimental Borna disease. The onset of
      disease was dependent on the cell numbers transferred and was clearly related to
      the appearance of T cells in the brain. CD8+ T cells were found in the
      parenchyma, whereas CD4+ T cells were found predominantly in perivascular
      locations. A disseminated lymphocytic infiltration in the parenchyma was
      accompanied by severe morphological alterations, including significant necrosis
      of neurons. Furthermore, a prominent spongiform-like degeneration was observed;
      this increased over time and finally resulted in severe cortical brain atrophy.
      Lymphocytes obtained during the beginning chronic phase of experimental Borna
      disease in rats had no significant cytolytic capacity in vitro and were also not
      able to induce neurological symptoms typical of Borna disease after adoptive
      transfer. The data presented here show for the first time that lymphocytes
      isolated from the site of the inflammatory lesions, namely, the brains of
      diseased rats, induce the immunopathological reaction and cause Borna disease.
      After transfer, the pathological alterations induced in the recipients exactly
      reflect those observed during experimentally induced Borna disease in rats,
      including necrosis of neurons and glial cells and gross degeneration resulting in
      cortical brain atrophy. Evidence that the immunopathology of Borna disease is
      closely related to the presence of CD8+ T cells in the brain parenchyma is
      provided.

PMID- 9032378
TI  - Effect of the E4 region on the persistence of transgene expression from
      adenovirus vectors.
AB  - The utility of adenovirus vectors for gene therapy is limited by the transience
      of expression that has been observed in various in vivo models. Immunological
      responses to viral targets can eliminate transduced cells and cause the loss of
      transgene expression. We previously described the characterization of an E4
      modified adenovirus, Ad2E4ORF6, which is replication defective in cotton rats. We
      reasoned that gene transfer vectors based on Ad2E4ORF6 would have a reduced
      potential for viral gene expression in vivo which might be beneficial for
      achieving persistence of transgene expression. E1 replacement vectors expressing
      the cystic fibrosis transmembrane regulator or beta-galactosidase were
      constructed as series of vectors that differed with respect to the E4 region.
      Vectors containing a wild-type E4 region, E4 open reading frame 6, or a complete
      E4 deletion were compared in the lungs of BALB/c mice for persistence of
      expression. Results obtained with nude mice indicate that nonimmunological
      factors have a major influence on the longevity of transgene expression.
      Expression was transient from the E1a promoter with all vectors but persisted
      from the cytomegalovirus promoter only with a vector containing a wild-type E4
      region. Transience of expression did not correlate with the disappearance of
      vector DNA, suggesting that promoter down-regulation may be involved. Coinfection
      studies indicate an E4 product(s) could be supplied in trans to allow persistent
      expression from the cytomegalovirus promoter. In summary, the choice of promoter
      is important for achieving persistence of expression; in addition, some promoters
      are highly influenced by the context of the vector backbone.

PMID- 9032379
TI  - Primary human immunodeficiency virus type 1 viremia and central nervous system
      invasion in a novel hu-PBL-immunodeficient mouse strain.
AB  - We established four new mouse strains with defective T and B cells as well as
      defects in innate immunological reactions using an NK cell depletion antibody and
      showed that all mutant mouse strains efficiently received human peripheral blood
      leukocyte (PBL) engraftment (hu-PBL-scid mice). Higher levels of human
      immunodeficiency virus type 1 (HIV-1) replication were observed in these new hu
      PBL-scid mice than in conventional hu-PBL-C.B-17-scid mice. In one particular
      strain, hu-PBL-NOD-scid mice, high levels of HIV-1 viremia (more than 10(6) 50%
      infectious doses per ml) were detected after infection with HIV-1. The plasma
      viral load was about 100 to 1,000 times higher than that observed in other hu-PBL
      scid mice infected with HIV-1. Although high-level viremia did not correlate with
      the total amount of HIV-1 RNA in cells from infected mice, high levels of free
      virions were detected only in hu-PBL-NOD-scid mice. HIV-1 viremia induced
      systemic HIV-1 infection involving the liver, lungs, and brain. PCR in situ
      hybridization confirmed that HIV-1-infected cells invaded the brain tissue of the
      hu-PBL-NOD-scid mice. Our results suggest that the genetic background, including
      innate immunity, is critical in the development of primary HIV-1 viremia and
      subsequent central nervous system invasion with HIV-1. The hu-PBL-NOD-scid mouse
      represents a useful model for the study of the pathogenesis of HIV-1 in vivo,
      especially brain involvement, and therapy of primary HIV-1 viremia.

PMID- 9032380
TI  - The transneuronal spread phenotype of herpes simplex virus type 1 infection of
      the mouse hind footpad.
AB  - The mouse hind footpad inoculation model has served as a standard laboratory
      system for the study of the neuropathogenesis of herpes simplex virus type 1 (HSV
      1) infection. The temporal and spatial distribution of viral antigen, known as
      the transneuronal spread phenotype, has not previously been described; nor is it
      understood why mice develop paralysis in an infection that involves sensory
      nerves. The HSV-as-transneuronal-tracer experimental paradigm was used to define
      the transneuronal spread of HSV-1 in this model. A new decalcification technique
      and standard immunocytochemical staining of HSV-1 antigens enabled a detailed
      analysis of the time-space distribution of HSV-1 in the intact spinal column.
      Mice were examined on days 3, 4, 5, and 6 postinoculation (p.i.) of a lethal dose
      of wild-type HSV-1 strain 17 syn+. Viral antigen was traced retrograde into first
      order neurons in dorsal root ganglia on day 3 p.i., to the dorsal spinal roots on
      days 4 and 5 p.i., and to second- and third-order neurons within sensory regions
      of the spinal cord on days 5 and 6 p.i. HSV-1 antigen distribution was localized
      to the somatotopic representation of the footpad dermatome within the dorsal root
      ganglia and spinal cord. Antigen was found in the spinal cord gray and white
      matter sensory neuronal circuits of nociception (the spinothalamic tract) and
      proprioception (the dorsal spinocerebellar tract and gracile fasciculus). Within
      the brain stems and brains of three paralyzed animals examined late in infection
      (days 5 and 6 p.i.), HSV antigen was restricted to the nucleus subcoeruleus
      region bilaterally. Since motor neurons were not directly involved, we postulate
      that hindlimb paralysis may have resulted from intense involvement of the
      posterior column (gracile fasciculus) in the thoracolumbar spinal cord, a region
      known to contain the corticospinal tract in rodents.

PMID- 9032381
TI  - The refined crystal structure of the 3C gene product from hepatitis A virus:
      specific proteinase activity and RNA recognition.
AB  - The virally encoded 3C proteinases of picornaviruses process the polyprotein
      produced by the translation of polycistronic viral mRNA. The X-ray
      crystallographic structure of a catalytically active mutant of the hepatitis A
      virus (HAV) 3C proteinase (C24S) has been determined. Crystals of this mutant of
      HAV 3C are triclinic with unit cell dimensions a = 53.6 A, b = 53.5 A, c = 53.2
      A, alpha = 99.1 degrees, beta = 129.0 degrees, and gamma = 103.3 degrees. There
      are two molecules of HAV 3C in the unit cell of this crystal form. The structure
      has been refined to an R factor of 0.211 (Rfree = 0.265) at 2.0-A resolution.
      Both molecules fold into the characteristic two-domain structure of the
      chymotrypsin-like serine proteinases. The active-site and substrate-binding
      regions are located in a surface groove between the two beta-barrel domains. The
      catalytic Cys 172 S(gamma) and His 44 N(epsilon2) are separated by 3.9 A; the
      oxyanion hole adopts the same conformation as that seen in the serine
      proteinases. The side chain of Asp 84, the residue expected to form the third
      member of the catalytic triad, is pointed away from the side chain of His 44 and
      is locked in an ion pair interaction with the epsilon-amino group of Lys 202. A
      water molecule is hydrogen bonded to His 44 N(delta1). The side-chain phenolic
      hydroxyl group of Tyr 143 is close to this water and to His 44 N(delta1) and may
      be negatively charged. The glutamine specificity for P1 residues of substrate
      cleavage sites is attributed to the presence of a highly conserved His 191 in the
      S1 pocket. A very unusual environment of two water molecules and a buried
      glutamate contribute to the imidazole tautomer believed to be important in the P1
      specificity. HAV 3C proteinase has the conserved RNA recognition sequence KFRDI
      located in the interdomain connection loop on the side of the molecule
      diametrically opposite the proteolytic site. This segment of polypeptide is
      located between the N- and C-terminal helices, and its conformation results in
      the formation of a well-defined surface with a strongly charged electrostatic
      potential. Presumably, this surface of HAV 3C participates in the recognition of
      the 5' and 3' nontranslated regions of the RNA genome during viral replication.

PMID- 9032382
TI  - Identification of the alpha6 integrin as a candidate receptor for
      papillomaviruses.
AB  - Papillomaviruses (PVs) bind in a specific and saturable fashion to a range of
      epithelial and other cell lines. Treatment of cells with trypsin markedly reduces
      their ability to bind virus particles, suggesting that binding is mediated via a
      cell membrane protein. We have investigated the interaction of human PV type 6b
      L1 virus-like particles (VLPs) with two epithelial cell lines, CV-1 and HaCaT,
      which bind VLPs, and a B-cell line (DG75) previously shown not to bind VLPs.
      Immunoprecipitation of a mixture of PV VLPs with [35S]methionine-labeled cell
      extracts and with biotin-labeled cell surface proteins identified four proteins
      from CV-1 and HaCaT cells of 220, 120, 87, and 35 kDa that reacted with VLPs and
      were not present in DG75 cells. The alpha6beta4 integrin complex has subunits
      corresponding to the VLP precipitated proteins, and the tissue distribution of
      this complex suggested that it was a candidate human PV receptor. Monoclonal
      antibodies (MAbs) to the alpha6 or beta4 integrin subunits precipitated VLPs from
      a mixture of CV-1 cell proteins and VLPs, whereas MAbs to other integrin subunits
      did not. An alpha6 integrin-specific MAb (GoH3) inhibited VLP binding to CV-1 and
      HaCaT cells, whereas an anti-beta4 integrin MAb and a range of integrin-specific
      and other MAbs did not. Furthermore, human laminin, the natural ligand for the
      alpha6beta4 integrin, was able to block VLP binding. By use of sections of monkey
      esophagus, the distribution of alpha6 integrin expression in the basal epithelium
      was shown to coincide with the distribution of bound VLPs. Taken together, these
      data suggest that VLPs bind specifically to the alpha6 integrin subunit and that
      integrin complexes containing alpha6 integrin complexed with either beta1 or
      beta4 integrins may act as a receptor for PV binding and entry into epithelial
      cells.

PMID- 9032384
TI  - Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide
      perspective.
AB  - We examined intratype human papillomavirus type 16 (HPV-16) sequence variation in
      tumor samples that were collected and analyzed in an international study of
      invasive cervical cancer. The collection included tumors from 22 countries in
      five continents. Using our recently developed E6 and L1 PCR-based hybridization
      systems to distinguish HPV-16 variant lineages, we analyzed material from tumors
      previously found to contain HPV-16 DNA. Of 408 specimens analyzed in the E6
      hybridization assay, 376 (92.2%) belonged to previously reported HPV-16 variant
      lineages. The remaining 32 specimens (7.8%) harbored HPV-16 variants with novel
      hybridization patterns, novel nucleotide changes, or both. Nucleotide sequences
      (1,203 bp) were determined for the E6, the MY09/11 region of L1, and the long
      control region of each novel variant and representative specimens from each
      hybridization pattern observed. Based on E6 hybridization patterns, most of the
      variants from European and North American samples were phylogenetically
      classified as European prototype (E) while samples from Africa contained
      primarily African 1 (Af1) or African 2 (Af2) variants. The majority of Asian (As)
      variants were observed in Southeast Asia, and almost all Asian American (AA)
      variants were from Central and South America or Spain. A single North American 1
      (NA1) variant was detected in a tumor from Argentina. Nucleotide changes
      previously shown to covary between the MY09/11 region of L1 and the E6 coding
      region were examined in a subset of 249 specimens. We observed 22 combined E6-L1
      hybridization patterns, of which 11 (in 21 samples) were novel. No unanticipated
      nucleotide covariation was observed between the E class and the AA-Af1-Af2-NA1
      classes, suggesting the absence or rarity of genomic recombination between HPV-16
      lineages. This extensive description of HPV-16 variants forms a basis for further
      examining the relationship between intratype variation and basic functional
      differences in biological activities. HPV-16 variants may prove important for the
      determination of the risk of cervical neoplasia and for the design of HPV-16
      vaccine strategies.

PMID- 9032383
TI  - A neutralizing monoclonal antibody previously mapped exclusively on human
      immunodeficiency virus type 1 gp41 recognizes an epitope in p17 sharing the core
      sequence IEEE.
AB  - We report here that a human immunodeficiency virus type 1 (HIV-1)-specific
      neutralizing monoclonal antibody (MAb 1575) mapped to the conserved putative
      intracellular region from amino acid residues 735 to 752 (735-752 region) of gp41
      also recognizes a region in an extracellular portion of p17. Both epitopes have a
      core recognition sequence (IEEE) in a nonhomologous context. The IEEE motif found
      in HIV-1 p17 is located in a region known as HGP-30 (residues 86 to 115) which
      has been previously associated with virus neutralization, cytotoxic T lymphocyte
      activity, and mother-to-child transmission. An analysis of available gp41 and p17
      sequences demonstrates that in these regions both IEEE sequences are highly
      conserved in different HIV-1 clades. The presence of the IEEE epitope in p17
      allows us to explain some unexpected neutralizing characteristics of MAb 1575. In
      addition, the gp41 735-752 region has been previously reported both in intra- and
      extracellular locations. Our results suggest that the extracellular location was
      the result of cross-reactivity with p17.

PMID- 9032385
TI  - Phenotypically Vif- human immunodeficiency virus type 1 is produced by
      chronically infected restrictive cells.
AB  - The permissivity of CD4+ transformed T cells for the replication of human
      immunodeficiency virus type 1 (HIV-1) vif mutants varies widely between different
      cell lines. Mutant vif-negative viruses propagate normally in permissive CD4+
      cell lines but are unable to establish a productive infection in restrictive cell
      lines such as H9. As a consequence, elucidation of the function of Vif has been
      considerably hampered by the inherent difficulty in obtaining a stable source of
      authentically replication-defective vif-negative viral particles produced by
      restrictive cells. vif-negative, vpr-negative HIV-1 strain NDK stock, produced by
      the permissive SupT1 cell line, was used to infect restrictive H9 cells. By using
      a high multiplicity, infection of H9 cells was achieved, leading to persistent
      production of viral particles displaying a dramatically reduced infectious virus
      titer when measured in a single-cycle infectivity assay. Although these viral
      particles were unable to further propagate in H9 cells, they could replicate
      normally in CEM and SupT1 cells. Comparison of unprocessed and processed Gag
      proteins in the persistently produced vif-negative viral particles revealed no
      defect in the processing of polypeptide precursors, with no inversion of the
      Pr55gag/p24 ratio. In addition, there was no defect in Env incorporation for the
      vif-negative viral particles. Despite their apparently normal protein content,
      these particles were morphologically abnormal when examined by transmission
      electron microscopy, displaying a previously described abnormally condensed
      nucleoid. Chronically infected restrictive cell lines producing stable levels of
      phenotypically vif-negative HIV-1 particles could prove particularly useful in
      further studies on the function of Vif in the virus life cycle.

PMID- 9032386
TI  - Spontaneous establishment of an Epstein-Barr virus-infected fibroblast line from
      the synovial tissue of a rheumatoid arthritis patient.
AB  - An Epstein-Barr virus (EBV)-infected fibroblast line, designated DSEK, was
      spontaneously established from synovial tissue of a patient with rheumatoid
      arthritis (RA). DSEK cells expressed EBV nuclear antigens EBNA-1 and EBNA-2 and
      latent membrane protein LMP-1. Cell surface markers of DSEK cells were similar to
      those of EBV-negative fibroblast clones derived from synoviocytes and were
      negative for lymphocyte and macrophage markers. DSEK cells expressed CD44, CD58,
      and HLA-DR antigens and spontaneously produced interleukin-10 basic fibroblast
      growth factor and transforming growth factor beta1. These results indicate that
      rheumatoid synoviocytes can be a target for EBV infection and suggest that EBV
      may play a role in the pathogenesis of RA.

PMID- 9032387
TI  - Size variation within the second hypervariable region of the surface envelope
      gene of the bovine lentivirus BIV in experimentally and naturally infected
      cattle.
AB  - The bovine lentivirus also known as the bovine immunodeficiency-like virus (BIV)
      has conserved and hypervariable regions in the surface envelope (SU) gene. Size
      variation between isolates can be as large as 200 bp, mostly occurring in the
      second hypervariable (V2) gene region of the SU gene. The V2 region was cloned
      and sequenced from both experimentally and naturally infected cattle. Temporal
      evaluation of provirus from an experimentally inoculated cow showed two different
      sized variants that appeared over time. The variation appeared to result from a
      recombinational event resulting in an apparent direct repeat. Cloned proviral
      nucleotide sequence diversity increased over time. Virus that was cultured and
      then cloned and sequenced showed progressive change from the inoculum virus, but
      culturing reduced the diversity of the clones as compared with direct
      amplification of provirus from leukocyte samples from the cow. The quasispecies
      phenomenon was evident in clones sequenced from a cow naturally infected with
      BIV. Of 10 clones examined from the V2 region, 6 different-size clones were
      present with nine different patterns of sequence rearrangement. Sequence length
      of different clones varied by as much as 43 amino acids (aa), with 21- and 15-aa
      direct repeats accounting for most of the size variation. Similar to other
      lentiviruses, BIV appears to mutate rapidly, which may be important in viral
      persistence and pathogenesis.

PMID- 9032388
TI  - Utilization of nonhomologous minus-strand DNA transfer to generate recombinant
      retroviruses.
AB  - During reverse transcription, minus-strand DNA transfer connects the sequences
      located at the two ends of the viral RNA to generate a long terminal repeat. It
      is thought that the homology in the repeat (R) regions located at the two ends of
      the viral RNA sequences facilitate minus-strand DNA transfer. In this report, the
      effects of diminished R-region homology on DNA synthesis and virus titer were
      examined. A retrovirus vector, PY31, was constructed to contain the 5' and 3' cis
      acting elements from Moloney murine sarcoma virus and spleen necrosis virus.
      These two viruses are genetically distinct, and the two R regions contain little
      homology. In one round of replication, the PY31 titer was approximately 3,000
      fold lower than that of a control vector with highly homologous R regions. The
      molecular characteristics of the junctions of minus-strand DNA transfer were
      analyzed in both unintegrated DNA and integrated proviruses. Short stretches of
      homology were found at the transfer junctions and were likely to be used to
      facilitate minus-strand DNA transfer. Both minus-strand strong-stop DNA and weak
      stop DNA were observed to mediate strand transfer. The ability of PY31 to
      complete reverse transcription indicates that minus-strand DNA transfer can be
      used to join sequences from two different viruses to form recombinant viruses.
      These results suggest the provocative possibility that genetically distinct
      viruses can interact through this mechanism.

PMID- 9032389
TI  - Molecular determinants for cellular uptake of Tat protein of human
      immunodeficiency virus type 1 in brain cells.
AB  - We measured the cellular uptake of 125I-labeled full-length Tat (amino acids 1 to
      86) (125I-Tat(1-86)) and 125I-Tat(1-72) (first exon) in human fetal astrocytes,
      neuroblastoma cells, and human fetal neurons and demonstrated that the uptake of
      125I-Tat(1-72) without the second exon was much lower than that of 125I-Tat(1-86)
      (P < 0.01). This suggests an important role for the C-terminal region of Tat for
      its cellular uptake. 125I-Tat uptake could be inhibited by dextran sulfate and
      competitively inhibited by unlabeled Tat but not by overlapping 15-mer peptides,
      suggesting that Tat internalization is charge and conformationally dependent.
      Interestingly, one of 15-mer peptides, Tat(28-42), greatly enhanced 125I-Tat
      uptake. These findings are important for understanding the neuropathogenesis of
      human immunodeficiency virus type 1 infection and in the potential application of
      Tat for drug delivery to cells.

PMID- 9032390
TI  - Structure-based rationale for the rescue of systemic movement of brome mosaic
      virus by spontaneous second-site mutations in the coat protein gene.
AB  - We describe spontaneous second-site reversions within the coat protein open
      reading frame that rescue the systemic-spread phenotype and increase virion
      stability of a mutant of brome mosaic virus. Based on the crystal structure of
      the related cowpea chlorotic mottle virus, we show that the modified residues are
      spatially clustered to affect the formation of hexamers and pentamers and
      therefore virion stability.

PMID- 9032392
TI  - Antibody-mediated neutralization of primary isolates of human immunodeficiency
      virus type 1 in peripheral blood mononuclear cells is not affected by the initial
      activation state of the cells.
AB  - Antibody-mediated neutralization of human immunodeficiency virus type 1 (HIV-1)
      was evaluated with primary isolates and sera from infected individuals, using
      human peripheral blood mononuclear cells (PBMC) activated with phytohemagglutinin
      1 day after virus inoculation (resting-cell assay) or 2 days prior to virus
      inoculation (blast assay). Assays were performed exclusively with syncytium
      inducing (SI) isolates since non-SI isolates replicated poorly or not at all in
      the resting-cell assay. Ninety percent neutralization was difficult to achieve in
      both assays for most virus-serum combinations tested. Of particular note, virus
      replication in the absence of antibody was delayed 2 to 3 days in the resting
      cell assay. At least part of this delay was due to a decrease in virus
      infectivity; the 50% tissue culture infectious dose of primary isolates was 25 to
      30 times lower in the resting-cell assay than in the PBMC blast assay. When a
      broadly neutralizing serum and the same dilution of virus were used in both
      assays, neutralization was greater in the resting-cell assay than in the blast
      assay on day 7, but neutralization was equal in both assays when measurements
      were made 3 days sooner in the PBMC blast assay. Both assays had the same level
      of detection on day 7 when the amount of virus mixed with antibody and added to
      cells was standardized according to infectivity for the respective target cells.
      Thus, when the infectious dose was adjusted, the two assays were equally
      sensitive for detecting antibody-mediated neutralization of primary isolates of
      HIV-1. These results indicate that primary isolates of HIV-1 are difficult to
      neutralize in both assays and that the detection of neutralization is not
      affected by the initial activation state of PBMC.

PMID- 9032391
TI  - Strain variability among Kaposi sarcoma-associated herpesvirus (human herpesvirus
      8) genomes: evidence that a large cohort of United States AIDS patients may have
      been infected by a single common isolate.
AB  - Previous analysis of the majority of Kaposi's sarcoma (KS) tumors, in both AIDS
      and non-AIDS populations, has revealed the consistent presence of two small
      subsegments (open reading frame 25/26 [ORF25/26] and ORF75) of a novel human
      gamma class herpesvirus genome referred to as KSHV or HHV-8. We have carried out
      DNA sequence comparisons with DNAs encompassing a total of 2,500 bp each over
      three separate PCR-amplified fragments from KS lesions and body cavity-based
      lymphoma (BCBL) samples from 12 distinct patients, including four African and two
      classical or endemic non-AIDS KS samples. The results revealed differences at 37
      of 2,500 nucleotide positions (i.e., 1.5% overall variation). However, the 12 HHV
      8 genomes examined fell into three distinct but very narrow subgroupings (A, B,
      and C strains). All A strain isolates differed from B strain isolates at 16
      positions, but of the eight U.S. samples tested, six were A strains, and these
      differed at no more than two positions among them. Similarly, three of the four
      African samples were B strains, which differed from each other at only one
      position. The two C strain genomes also displayed only one nucleotide variation,
      but they differed from all A strains at 26 positions and from all B strains at 20
      positions. One C strain genome was present in all six independent lesions from an
      AIDS KS patient with disseminated disease, and the other represented a mosaic A/C
      recombinant genome from the HBL6 cell line derived from a BCBL tumor. Evaluation
      of previous data suggests that B and C strains may predominate in Africa and that
      A strains predominate in classical Mediterranean samples. Although both B and C
      strains are represented in U.S. AIDS patients, the majority (70 to 80%) of
      samples from the mid-East Coast region at least appear to be virtually identical,
      supporting the concept that they may all derive from the spread during the AIDS
      epidemic of a single recently transmitted infectious agent.

PMID- 9032393
TI  - Modification of the Sendai virus-specific antibody and CD8+ T-cell responses in
      mice homozygous for disruption of the interleukin-4 gene.
AB  - Homozygous disruption (-/-) of the interleukin-4 (IL-4) gene did not obviously
      modify the severity of Sendai virus infection in the highly susceptible 129/J
      mouse strain. The virus was cleared from the respiratory tract, and potent
      cytotoxic T lymphocyte (CTL) effectors were present in the cell population
      recovered by bronchoalveolar lavage. However, the prevalence of virus-specific
      CTL precursors (p) was consistently diminished in the spleen and regional lymph
      nodes of the IL-4 -/- mice at day 7 after infection. Also, virus-specific serum
      immunoglobulin G1 (IgG1) levels were greatly reduced and few IgG1-producing cells
      were detected in the lymphoid tissue. The effect on IgG1 class switching was to
      be expected, but the decrease in CTLp numbers has not been observed previously
      for a virus-specific immune response.

PMID- 9032394
TI  - Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a
      pathogenic simian immunodeficiency virus, SIVmac239.
AB  - We examined chemokine receptors for the ability to facilitate the infection of
      CD4-expressing cells by viruses containing the envelope glycoproteins of a
      pathogenic simian immunodeficiency virus, SIVmac239. Expression of either human
      or simian C-C chemokine receptor CCR5 allowed the SIVmac239 envelope
      glycoproteins to mediate virus entry and cell-to-cell fusion. Thus, distantly
      related immunodeficiency viruses such as SIV and the primary human
      immunodeficiency virus type 1 isolates can utilize CCR5 as an entry cofactor.

PMID- 9032395
TI  - Binding sites for adeno-associated virus Rep proteins within the human genome.
AB  - The Rep proteins of adeno-associated virus type 2 (AAV) are known to bind to Rep
      recognition sequences (RRSs) in the AAV inverted terminal repeats (ITRs), the AAV
      p5 promoter, and the preferred AAV integration site in human chromosome 19,
      called AAVS1. Integration of the AAV genome into AAVS1 appears to be mediated by
      an interaction between the Rep proteins of AAV and Rep binding sites within the
      viral genome and the integration locus. In an attempt to identify potential
      alternate integration sites, we looked for recognition sites for AAV Rep proteins
      in the human genome by performing a BLASTN computerized homology search. We used
      the 16-mer core sequences of the RRSs in the AAV ITRs and AAVS1 separately as
      query sequences and identified 18 new RRSs in or flanking the genes coding for
      the following: tyrosine kinase activator protein 1 (TKA-1); colony stimulating
      factor-1; insulin-like growth factor binding protein 2 (IGFBP-2); histone H2B.1;
      basement membrane heparan sulfate proteoglycan, also known as perlecan; the AF-9
      gene product, which is involved in the chromosomal translocation t
      (9:11)(p22:q23); the betaB subunit of the hormone known as inhibin; interleukin-2
      enhancer binding factor; an endoplasmic reticulum-Golgi intermediate compartment
      resident protein called p63; a global transcription activator (hSNF2L); the beta
      actin repair domain; a retinoic acid-inducible factor, also known as midkine; a
      breast tumor autoantigen; a growth-arrest- and DNA-damage-inducible protein
      called gadd45; the cyclin-dependent kinase inhibitor called KIP2, which inhibits
      several G1 cyclin-cyclin-dependent kinase complexes; and the hereditary breast
      and ovarian cancer gene (BRCA1). RRSs were also identified in a newly discovered
      open reading frame on chromosome 10 and in the ERCC1 locus on human chromosome
      19. The ability of a maltose binding protein-Rep68 fusion protein to bind to
      these sequences was confirmed by electrophoretic mobility shift assays. These
      sites may serve as alternate integration sites for AAV or play a role in Rep
      mediated effects on human cells.

PMID- 9032396
TI  - Induction of phosphorylation of human immunodeficiency virus type 1 Nef and
      enhancement of CD4 downregulation by phorbol myristate acetate.
AB  - The nef gene of the human and simian immunodeficiency viruses (HIV and SIV)
      encodes a 27 to 34 kDa myristoylated protein that induces downregulation of CD4
      from the cell surface and enhances virus infectivity. As shown by experiments on
      SIV-infected adult macaques, Nef is important in pathogenesis and disease
      progression. In vitro, protein kinase C (PKC) phosphorylates Nef, but the role of
      phosphorylation in the function and expression of this protein has not yet been
      determined. Here we show that in HIV type 1-infected cells, phosphorylation of
      Nef increased 8- to 12-fold after treatment with phorbol myristate acetate and
      phytohemagglutinin (PMA/PHA). Basal and PMA/PHA-induced phosphorylation occurred
      on serine residues of Nef and was independent of other HIV proteins. The PMA/PHA
      induced phosphorylation of Nef was inhibited by bisindolylmaleimide I, a potent
      and specific inhibitor of PKC, but was unaffected by H89, an inhibitor of protein
      kinase A. In contrast, treatment with bisindolylmaleimide I did not affect the
      basal level of Nef phosphorylation, suggesting two different phosphorylation
      pathways. A PMA-insensitive CD4 mutant in which three serine residues in the
      cytoplasmic domain have been replaced by alanines was used to determine whether
      PMA-induced phosphorylation affects Nef-induced CD4 downregulation. In Nef
      expressing cells, treatment with PMA enhanced downregulation of the CD4 serine
      triple mutant from the cell surface, suggesting that phosphorylation is important
      for Nef function.

PMID- 9032398
TI  - Reed-Sternberg cells and "bystander" lymphocytes in lymph nodes affected by
      Hodgkin's disease are infected with different strains of Epstein-Barr virus.
AB  - In most cases of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD), EBV
      positive Reed-Sternberg (RS) cells and rare EBV-positive reservoir lymphocytes
      coexist in lymph nodes. Here we show that, in two cases of EBV-associated HD,
      strains infecting RS cells and reservoir lymphocytes of the same patient have
      different BNLF-1 genes. This suggests that RS cells and reservoir lymphocytes of
      the same patient are infected by different EBV strains.

PMID- 9032397
TI  - Reovirus-induced apoptosis of MDCK cells is not linked to viral yield and is
      blocked by Bcl-2.
AB  - In this study, we investigated the relationship between reovirus-induced
      apoptosis and viral growth. Madin-Darby canine kidney (MDCK) epithelial cells
      infected with prototype reovirus strains type 1 Lang (T1L) or type 3 Dearing
      (T3D) were found to undergo apoptosis, and T3D induced apoptosis of MDCK cells to
      a substantially greater extent than T1L. By using T1L x T3D reassortant viruses,
      we found that differences in the capacities of these strains to induce apoptosis
      are determined by the viral S1 and M2 gene segments. These genes encode viral
      outer-capsid proteins that play important roles in viral entry into cells. T1L
      grew significantly better in MDCK cells than T3D, and these differences in growth
      segregated with the viral L1 and M1 gene segments. The L1 and M1 genes encode
      viral core proteins involved in viral RNA synthesis. Bcl-2 overexpression in MDCK
      cells inhibited reovirus-induced apoptosis but did not substantially affect
      reovirus growth. These findings indicate that differences in the capacities of
      reovirus strains to induce apoptosis and grow in MDCK cells are determined by
      different viral genes and that premature cell death by apoptosis does not limit
      reovirus growth in MDCK cells.

PMID- 9032399
TI  - The herpesvirus saimiri ORF50 gene, encoding a transcriptional activator
      homologous to the Epstein-Barr virus R protein, is transcribed from two distinct
      promoters of different temporal phases.
AB  - The mRNA species encoding the herpesvirus saimiri (HVS) homolog of the Epstein
      Barr virus R transcriptional activator (termed ORF50) have been identified and
      used to determine transcriptional start sites within the gene. The first
      transcript is spliced and starts from a promoter within ORF49 containing a single
      intron; the second is produced from a promoter within the second exon and is in
      the same reading frame. The spliced transcript is detected at early times during
      productive virus replication in OMK cells, whereas the nonspliced transcript is
      detected later. The spliced transcript is fivefold-more potent in activating the
      delayed-early ORF6 promoter; the function of the nonspliced transcript is
      unclear. Thus, the role of this protein in activating herpesvirus saimiri from
      the latent state may differ significantly from that of the Epstein-Barr virus R
      protein.

PMID- 9032401
TI  - Mapping and characterization of the origin of DNA replication of porcine
      circovirus.
AB  - The origin of DNA replication of porcine circovirus (PCV) was mapped to a 111-bp
      fragment. On top of a hairpin, a nonanucleotide (TAGTATTAC) homologous to
      nonanucleotides of other viruses was identified. Mutation of this element
      abolishes replication. PCV may be related to a virus family characterized by
      single-stranded circular DNA genomes, rolling-circle replication, and homology of
      their rep proteins.

PMID- 9032400
TI  - Host-specific driving force in human immunodeficiency virus type 1 evolution in
      vivo.
AB  - To investigate the process of human immunodeficiency virus type 1 (HIV-1)
      evolution in vivo, a total of 179 HIV-1 V3 sequences derived from cell-free
      plasma were determined from serial samples in three epidemiologically linked
      individuals (one infected blood donor and two transfusion recipients) over a
      maximum period of 8 years. A systematic analysis of pairwise comparisons of
      intrapatient sequences, both within and between each sample time point, revealed
      a preponderance and accumulation of nonsynonymous rather than synonymous
      substitutions in the V3 loop and flanking regions as they diverged over time.
      This strongly argues for the dominant role that positive selection for amino acid
      change plays in governing the pattern and process of HIV-1 env V3 evolution in
      vivo and nullifies hypotheses of purely neutral or mutation-driven evolution or
      completely chance events. In addition, different rates of evolution of HIV-1 were
      observed in these three different individuals infected with the same viral
      strain, suggesting that the degree of positive pressure for HIV-1 amino acid
      change is host dependent. Finally, the observed similar rate of accumulation in
      divergence within and between infected individuals suggests that the process of
      genetic divergence in the HIV epidemic proceeds regardless of host-to-host
      transmission events, i.e., that transmission does not reset the evolutionary
      clock.

PMID- 9032402
TI  - Suppression of apoptotic DNA fragmentation in herpes simplex virus type 1
      infected cells.
AB  - HEp-2 cells underwent apoptosis when the cells were incubated in medium
      containing sorbitol. Infection with herpes simplex virus type 1 (HSV-1) prior to
      the sorbitol treatment suppressed this apoptosis completely, indicating that HSV
      1 carries an antiapoptosis gene. In addition, HSV-1 multiplication was restricted
      in these apoptotic HEp-2 cells.

PMID- 9032403
TI  - Identification of nucleotide sequences that regulate transcription of the MCF13
      murine leukemia virus long terminal repeat in activated T cells.
AB  - The region downstream of the enhancer (DEN) of the long terminal repeat of the
      mink cell focus-forming murine leukemia virus is important for viral
      pathogenicity. Another important activity of DEN is its control of transcription
      in activated T cells, and we have determined that an NF-kappaB site is critical
      for this activity.

PMID- 9032404
TI  - In vitro transcription of human T-cell leukemia virus type 1 is RNA polymerase II
      dependent.
AB  - The HTLV-1 promoter directs RNA polymerase II transcription of viral genomic RNA
      in vivo. However, it has been reported that in vitro, a unique RNA polymerase,
      with characteristics of RNA polymerases II and III, is capable of HTLV-1
      transcription (G. Piras, F. Kashanchi, M. F. Radonovich, J. F. Duvall, and J. N.
      Brady, J. Virol. 68:6170-6179, 1994). To further characterize the polymerase
      involved in HTLV-1 transcription in vitro, runoff transcription assays were
      performed with a variety of extracts and RNA polymerase inhibitors. Under all in
      vitro reaction conditions tested, RNA polymerase II appeared to be the only
      polymerase capable of correct transcriptional initiation from the HTLV-1
      promoter. Synthesis of the specific HTLV-1 RNA transcript showed sensitivities to
      the RNA polymerase inhibitors tagetitoxin and alpha-amanitin that are consistent
      with RNA polymerase II transcription. Together, these data indicate that in
      vitro, as in vivo, the HTLV-1 promoter directs transcription by RNA polymerase
      II.

PMID- 9032405
TI  - Large scale isolation of intact rat basophilic leukemia (RBL-2H3) cells.
AB  - The rat basophilic leukemia RBL-2H3 mast cell line is widely used for studies of
      the structure and function of the high affinity IgE receptor (Fc epsilonRI). Here
      we report on a simple method to isolate large numbers of intact RBL-2H3 cells
      from tumors produced by injection of the cells into newborn rats. Collagenase
      treatment of rat tumors yields approximately 3.5 x 10(8) viable cells/animal.
      Aggregating Fc epsilonRI on these cells induced tyrosine phosphorylation of
      proteins including the protein tyrosine kinase Syk. This procedure should prove
      useful for the isolation and characterization of cellular molecules important for
      mast cell and basophil function.

PMID- 9032406
TI  - Fluorescence depolarization as an early measure of T lymphocyte stimulation.
AB  - We have used the Cellscan, an apparatus capable of measuring optical properties
      of individual cells, to study changes in fluorescence polarization associated
      with T cell stimulation. We show that the fluorescence polarization of human
      peripheral blood lymphocytes (PBL) labeled with fluorescein diacetate (FDA) is
      markedly reduced upon exposure to the mitogenic lectins phytohemagglutinin (PHA),
      concanavalin A (ConA), or to phorbol esters. Methyl alpha-D-mannopyranoside
      (alphaMM) is able to reverse the depolarizing effect induced by ConA as long as
      the cells are not committed to proliferate. H7 and staurosporin, both inhibitors
      of protein kinase C (PKC), inhibit the depolarization induced by PHA. The mitogen
      induced depolarization is dependent on metabolic energy. The results support the
      use of fluorescence depolarization of FDA-labeled PBL, monitored by the Cellscan,
      as a sensitive means of measuring early lymphocyte stimulation.

PMID- 9032407
TI  - Engineering of Fc(1) and Fc(3) from human immunoglobulin G to analyse subclass
      specificity for staphylococcal protein A.
AB  - A system for production of recombinant Fc fragments of human IgG in Escherichia
      coli has been developed to allow for structural and functional studies of human
      Fc. The genes for the Fc fragments of human IgG subclasses 1 and 3, designated
      Fc(1) and Fc(3), were cloned from a human spleen cDNA library. The interactions
      to Staphylococcal protein A (SpA), a bacterial Fc receptor, that interacts with
      human IgG-Fc(1), but not with human IgG-Fc(3), were analyzed. To corroborate the
      involvement of amino acid residues in Fc, responsible for these differences in
      binding, two Fc variants were constructed; Fc(1(3)) and Fc(3(1)), each containing
      an isotypic dipeptide substitution. Production levels in E. coli of 1-10 mg/l of
      secreted Fc proteins, covalently linked as dimers, were routinely obtained. SpA
      binding analyses of all four Fc variants using biosensor technology, showed that
      Fc(1) and Fc(3(1)) interact with SpA, while Fc(3) and Fc(1(3)) lack detectable
      SpA binding. The rendered SpA binding of the Fc variant Fc(3(1)), is concluded to
      result from the introduced dipeptide substitution (R435H, F436Y). The results
      demonstrate that the Fc expression system efficiently can be used in Fc
      engineering.

PMID- 9032408
TI  - Reliable cloning of functional antibody variable domains from hybridomas and
      spleen cell repertoires employing a reengineered phage display system.
AB  - A prerequisite for the use of recombinant antibody technologies starting from
      hybridomas or immune repertoires is the reliable cloning of functional
      immunoglobulin genes. For this purpose, a standard phage display system was
      optimized for robustness, vector stability, tight control of scFv-delta geneIII
      expression, primer usage for PCR amplification of variable region genes, scFv
      assembly strategy and subsequent directional cloning using a single rare cutting
      restriction enzyme. This integrated cloning, screening and selection system
      allowed us to rapidly obtain antigen binding scFvs derived from spleen-cell
      repertoires of mice immunized with ampicillin as well as from all hybridoma cell
      lines tested to date. As representative examples, cloning of monoclonal
      antibodies against a his tag, leucine zippers, the tumor marker EGP-2 and the
      insecticide DDT is presented. Several hybridomas whose genes could not be cloned
      in previous experimental setups, but were successfully obtained with the present
      system, expressed high amounts of aberrant heavy and light chain mRNAs, which
      were amplified by PCR and greatly exceeded the amount of binding antibody
      sequences. These contaminating variable region genes were successfully eliminated
      by employing the optimized phage display system, thus avoiding time consuming
      sequencing of non-binding scFv genes. To maximize soluble expression of
      functional scFvs subsequent to cloning, a compatible vector series to simplify
      modification, detection, multimerization and rapid purification of recombinant
      antibody fragments was constructed.

PMID- 9032409
TI  - Quantitative analysis of the products of IgG chain recombination in hybrid
      hybridomas based on affinity chromatography and radioimmunoassay.
AB  - On the model of a hybrid hybridoma (quadroma) to alpha-endorphin (END) and
      horseradish peroxidase (HRP), we have elaborated a general approach to analyse H
      and L chain interactions in hybrid hybridomas and to evaluate their efficiency as
      producers of bispecific antibodies (bAbs). This strategy is based on quantitative
      analysis of quadroma produced Abs by affinity chromatography and
      radioimmunoassay. First, Abs produced by quadroma cells in culture media (IgG
      pools from three quadroma clones) were fractioned with respect to specificity.
      Second, Ab concentrations in each fraction (bispecific, anti-END, anti-HRP and
      inactive) were measured by specific radioimmunoassays, using rabbit antiserum
      against mouse IgG and 125I-labelled affinity purified quadroma Abs. Then the
      experimentally obtained Ab distributions were compared with the predicted Ab
      distributions for different models of IgG chain recombination in quadroma cells
      (random H/L pairing, preferential homologous H/L association). As follows from
      these models, in a random H/L recombination the yield of bAbs in quadroma
      produced IgG cannot exceed 12.5%, and the ratio of bAbs and inactive Abs cannot
      exceed 0.5. In the analysed clones the yield of bAbs amounted to about 30% of
      total IgG, and the ratio of bAbs and inactive Abs was about 5-8, giving strong
      evidence for preferential homologous H/L association in these cells. The ratio of
      anti-HRP and anti-END Abs was about 10:1, suggesting unequal production of
      parental IgG chains in quadroma cells. The result of quantitative analysis of
      quadroma IgG was further supported by two-dimensional gel analysis of affinity
      purified fractions of quadroma IgG and of two parental mAbs.

PMID- 9032410
TI  - High-level secretion of two antibody single chain Fv fragments by Pichia
      pastoris.
AB  - The diagnostic and therapeutic applications of antibody single-chain Fv (sFv)
      fragments often require large amounts of protein that can be problematic and
      expensive to obtain. Here we report the secretion of two sFv fragments by the
      yeast Pichia pastoris at levels up to 250 mg/l. Soluble sFv fragments were
      purified from culture supernatants in one step by affinity or metal-chelating
      chromatography, and were indistinguishable from their bacterially expressed
      counterparts in terms of affinity. Secretion of functional sFv fragments by
      Pichia pastoris provides a low cost, high yield alternative to current sFv
      expression systems.

PMID- 9032411
TI  - Site-specific photobiotinylation of immunoglobulins, fragments and light chain
      dimers.
AB  - Herein we report a new method to rapidly photoinsert biotin into a specific and
      highly conserved site on the Ig structure using a mild photochemical activation
      step. This site resides in the Fv fragment and involves invariant residues which
      provide base stacking interactions to the purine ring of ATP (Rajagopalan et al.
      (1996) Proc. Natl. Acad. Sci. USA 93, 6019-6024). Biotin was coupled to either
      the phosphate or the ribose of the 8-azidopurine nucleotide or nucleoside
      photoaffinity probe and shown to insert into the affinity site efficiently.
      Several monoclonal and polyclonal antibodies, as well as enzymatic and
      recombinant antibody fragments and light chain dimers were photoaffinity
      biotinylated and used in ELISA, FACS and Western blots. The selectivity of this
      site-specific biotinylation method also allows for biotinylation of antibodies in
      culture supernatants and immune sera without prior purification. Because the
      biotinylation takes place under physiological conditions and within a short time
      period, photobiotinylation would be the preferred method for antibodies which are
      easily damaged by classical non-site specific random biotinylation chemistry.

PMID- 9032412
TI  - Counterimmunoelectrophoresis with serum prediffusion: an improved method for the
      detection and identification of antibodies against extractable nuclear and
      cytoplasmic antigens.
AB  - In the technique of counterimmunoelectrophoresis (CIE) with serum prediffusion
      (SPD) serum is allowed to diffuse freely into the gel before pouring the
      antigenic extract in its trough (or wells) and starting the electrophoresis. Both
      the immunoprecipitations and the interactions with reference sera are strongly
      intensified by SPD, leading to higher sensitivity and specificity for the
      detection of anti-SSA/Ro, anti-SSB/La, anti-U1RNP, anti-Sm, anti-Jo1 and even
      anti-Scl-70 antibodies. We found that the optimal SPD time was 2 h. To evaluate
      the relevance of SPD for the clinical laboratory, 92 antinuclear antibody (ANA)
      positive sera were tested on CIE without SPD and with 2 h SPD in identification
      tests with SSA/Ro, SSB/La, Sm, U1RNP and Jo1 reference sera (rsa). The
      precipitation lines and their interactions were evaluated by three independent
      observers. It was observed that SPD considerably improved the efficiency of CIE
      for antibody identification. The mechanisms underlying the intensification of the
      precipitation lines by SPD are discussed as are the characteristics of the CIE in
      comparison with other test systems such as the enzyme linked immunosorbent assay
      (ELISA) and immunoblot.

PMID- 9032413
TI  - Statistical analysis of highly skewed immune response data.
AB  - This paper considers methods of statistical analysis for highly skewed immune
      response data. Observations from population studies of immunological variables
      are rarely normally distributed between individuals; typically the distribution
      shows extreme levels of skewness. In some situations, skewness remains
      considerable even after transforming the data. Using resampling techniques,
      applied to several actual datasets of ELISA assay data, we consider the
      robustness of normal parametric methods, e.g. t tests and linear regression.
      Despite the skewness of the transformed data, we demonstrate that such methods
      are quite robust depending on the number of observations, type of analysis and
      severity of skewness. We also illustrate how bootstrap resampling can be used to
      provide a valid alternative method of analysis that can be used either for
      checking normal parametric analysis or as a direct method of analysis. We
      illustrate this combined approach by analysing real data to test for association
      between human serum antibodies to malaria merozoite surface proteins, MSP1 and
      MSP2, and resistance to clinical malaria, and confirm the protective effect of
      antibodies to MSP1 and demonstrated a similar protective effect for some
      antibodies to MSP2.

PMID- 9032414
TI  - The serum albumin-binding region of streptococcal protein G: a bacterial fusion
      partner with carrier-related properties.
AB  - In this study, we have explored the use of the serum albumin-binding region (BB)
      from streptococcal protein G (SpG) as a bacterial fusion partner for production
      of peptide immunogens. The fusion protein BB-M3, containing BB and repeated
      structures from the Plasmodium falciparum malaria antigen Pf155/RESA, was
      efficiently purified from Escherichia coli culture supernatants by affinity
      chromatography using BB as an affinity tag. Rabbits immunized with BB-M3 in
      Freund's adjuvant produced high levels of antibodies which reacted with both M3
      and BB in ELISA and stained intact Pf155/RESA in the membrane of infected
      erythrocytes. These antibody levels were sustained for more than 30 weeks. BB-M3
      also induced antibody responses to M3, BB and intact Pf155/RESA in a number of
      mouse strains, including several strains which are non-responders to the malaria
      sequences. In the latter mice, however, BB-M3 only activated BB-specific T cells,
      suggesting that BB has ability to provide carrier-related T cell help for
      antibody production. Moreover, the minimal albumin-binding motif of SpG,
      containing only 46 amino acids, was immunogenic in both B10.BR, B10.D2 and
      C57BL/6 mice (H-2k, H-2d and H-2b, respectively). These results indicate that BB
      has both affinity tag and carrier-related properties and suggest that fusion
      proteins containing BB can be efficient tools for the generation of antibody
      responses to peptides which are weak immunogens.

PMID- 9032415
TI  - Detection and quantification of cyclosporine in body fluids using an interleukin
      2 reporter-gene assay.
AB  - Different assays are employed to monitor the concentration of immunosuppressive
      drugs in biological fluids. None of these methods gives direct and precise
      information on the actual level of immunosuppression in the patient. Here we
      describe the use of an interleukin-2 (IL-2) reporter-gene assay (IL-2 RGA) to
      monitor the concentrations of immunosuppressants in body fluids. This assay is
      based on a chimeric gene construct in which the human IL-2 promoter drives the
      expression of a reporter gene. Upon mitogenic stimulation the reporter gene is
      expressed and can be easily quantified. The assay is very sensitive and selective
      for immunosuppressive compounds inhibiting IL-2 gene expression such as
      cyclosporine (CsA) and FK506, their active metabolites and derivatives, but not
      for others such as rapamycin. High reproducibility, fast performance time, and
      high capacity are additional characteristics of the assay. The assay was
      developed to monitor immunosuppressive drug levels in human volunteers or in
      animals receiving CsA analogues as the only immunosuppressive drugs. This assay
      is sensitive to CsA or ascomycin/FK506 analogues and metabolites, for which there
      are presently no specific monoclonal antibodies available. The IL-2 reporter-gene
      assay may be more suitable than other in vitro systems such as MLR or mitogen
      stimulated PBMC which were previously used to study the immunosuppressive
      activity of drugs in body fluids.

PMID- 9032438
TI  - Rapid kinetic measurements of 45Ca2+ mobilization reveal that Ins(2,4,5)P3 is a
      partial agonist at hepatic InsP3 receptors.
AB  - Ins(2,4,5)P3, a metabolically stable analogue of Ins(1,4,5)P3, is widely used in
      analyses of Ca2+ signalling pathways, but its utility depends upon it faithfully
      mimicking the effects of the natural messenger, Ins(1,4,5)P3, at InsP3 receptors.
      To compare the kinetics of InsP3-evoked 45Ca2+ mobilization, Ins(1,4,5)P3- and
      Ins(2,4,5)P3-stimulated 45Ca2+ release from the intracellular stores of
      permeabilized rat hepatocytes was measured using rapid superfusion. Both
      Ins(1,4,5)P3 and Ins(2,4,5)P3 caused concentration-dependent increases in the
      rate of 45Ca2+ efflux, which accelerated towards a peak and then abruptly
      switched to a bi-exponentially decaying release rate. However, the peak rate of
      45Ca2+ mobilization evoked by maximal concentrations of Ins(2,4,5)P3 was only
      65+/-3% (n = 3) of that evoked by Ins(1,4,5)P3. Furthermore, Ins(2,4,5)P3
      inhibited the peak rate of 45Ca2+ efflux evoked by Ins(1,4,5)P3. These results
      indicate that Ins(2,4,5)P3 is a partial agonist at hepatic Ins(1,4,5)P3
      receptors. Additionally, responses to Ins(2,4,5)P3 were less positively
      cooperative [Hill coefficient (h) = 1.9+/-0.3] than were those to Ins(1,4,5)P3 (h
      = 3.0+/-0.2) and the kinetics of termination of 45Ca2+ mobilization were slower.
      The lesser efficacy of Ins(2,4,5)P3 may account for the lower cooperativity in
      the responses it evokes, the slower inactivation of InsP3 receptors and the
      characteristic patterns of Ca2+ spiking it evokes in intact cells.

PMID- 9032439
TI  - The human fertilin alpha gene is non-functional: implications for its proposed
      role in fertilization.
AB  - In the guinea-pig, the alpha subunit of the fertilin complex, a heterodimeric
      surface membrane glycoprotein found on the head region of spermatozoa, has
      previously been proposed to mediate membrane fusion with the oolemma plasma
      membrane during fertilization. Here we describe experiments which indicate that
      the only fertilin alpha-like gene in humans is an expressed, but nonfunctional,
      pseudogene, possibly derived by genetic recombination between the two fertilin
      alpha genes found in some primates. This finding clearly raises questions about
      the importance and/or role of fertilin alpha in mammalian fertilization.

PMID- 9032440
TI  - Analysis of glycosylation sites on gp91phox, the flavocytochrome of the NADPH
      oxidase, by site-directed mutagenesis and translation in vitro.
AB  - Flavocytochrome b558 of the NADPH oxidase which generates superoxide in
      phagocytic cells, is a alpha1 beta1 heterodimer of gp91phox and p22phox, which
      together form a membrane-spanning electron-transport chain that transfers
      electrons from NADPH in the cytosol to oxygen. The C-terminal portion of gp91phox
      is a member of the ferredoxin-NADP+ reductase family of reductases. Little is
      known of the organization of the N-terminal section of this molecule, which is
      associated with the two haem structures. It is N-glycosylated, and site-directed
      mutagenesis has been used to eliminate the five potential N-linked glycosylation
      consensus sites. Mutated cDNAs were expressed in vitro. This approach provided
      evidence for glycosylation of residues Asn131, Asn148 and Asn239, but not of
      Asn96 and Asn429.

PMID- 9032442
TI  - Purification and characterization of paraoxon hydrolase from rat liver.
AB  - Paraoxonase (paraoxon hydrolase), an enzyme that hydrolyses paraoxon (O,O-diethyl
      O-p-nitrophenyl phosphate), is located in mammals primarily in the serum and
      liver. Although considerable information is available regarding serum
      paraoxonase, little is known about the hepatic form of this enzyme. The present
      work represents the first study on the purification of rat liver paraoxonase.
      This enzyme has been purified 415-fold to apparent homogeneity with a final
      specific activity of 1370 units/mg using a protocol consisting of five steps:
      solubilization of the microsomal fraction, hydroxyapatite adsorption,
      chromatography on DEAE-Sepharose CL-6B, non-specific affinity chromatography on
      Cibacron Blue 3GA and anion exchange on Mono Q HR 5/5. The presence of Ca2+ and
      Triton X-100 in the buffers throughout the purification procedure was essential
      for maintaining enzyme activity. SDS/PAGE of the final preparation indicated a
      single protein-staining band with an apparent Mr of 45 000. N-terminal and
      internal amino acid sequences were determined and compared with those of
      paraoxonases from human and rabbit serum and mouse liver, showing a high
      similarity. The pH profile showed optimum activity at pH 8.5. The pH stability
      and heat inactivation of the enzyme were also studied. The Km for liver
      paraoxonase was 1.69 mM.

PMID- 9032437
TI  - Signalling functions and biochemical properties of pertussis toxin-resistant G
      proteins.
AB  - Pertussis toxin (PTX) has been widely used as a reagent to characterize the
      involvement of heterotrimeric G-proteins in signalling. This toxin catalyses the
      ADP-ribosylation of specific G-protein alpha subunits of the Gi family, and this
      modification prevents the occurrence of the receptor-G-protein interaction. This
      review focuses on the biochemical properties and signalling of those G-proteins
      historically classified as 'PTX-resistant' due to the inability of the toxin to
      influence signalling through them. These G-proteins include members of the Gq and
      G12 families and one Gi family member, i.e. Gz. Signalling pathways controlled by
      these G-proteins are well characterized only for Gq family members, which
      activate specific isoforms of phospholipase C, resulting in increases in
      intracellular calcium and activation of protein kinase C (PKC), among other
      responses. While members of the G12 family have been implicated in processes that
      regulate cell growth, and Gz has been shown to inhibit adenylate cyclase, the
      specific downstream targets to these G-proteins in vivo have not been clearly
      established. Since two of these proteins, G12 alpha and Gz alpha, are excellent
      substrates for PKC, there is the potential for cross-talk between their
      signalling and Gq-dependent processes leading to activation of PKC. In tissues
      that express these G-proteins, a number of guanine-nucleotide-dependent, PTX
      resistant, signalling pathways have been defined for which the G-protein involved
      has not been identified. This review summarizes these pathways and discusses the
      evidence both for the participation of specific PTX-resistant G-proteins in them
      and for the regulation of these processes by PKC.

PMID- 9032441
TI  - PACE4: a subtilisin-like endoprotease with unique properties.
AB  - PACE4 is one of the neuroendocrine-specific mammalian subtilisin-related
      endoproteases believed to function in the secretory pathway. The biosynthesis and
      secretion of PACE4 have been studied using transfected neuroendocrine and
      fibroblast cell lines. as well as primary pituitary cultures. ProPACE4 (approx.
      106 kDa) is cleaved intracellularly before secretion of PACE4 (approx. 97 kDa);
      the N-terminal propeptide cleavage is accelerated in a truncated form of PACE4
      lacking the Cys-rich C-terminal region (PACE4s). Neither PACE4 nor PACE4s is
      stored in regulated neuroendocrine secretory granules, whereas pro
      opiomelanocortin-derived peptides and prohormone convertase I enter the regulated
      secretory pathway efficiently. The relatively slow cleavage of the proregion of
      proPACE4 in primary anterior pituitary cells, followed by rapid secretion of
      PACE4, is similar to the results for proPACE4 in transfected cell lines. The
      enzyme activity of PACE4 is distinct from furin and prohormone convertases, both
      in the marked sensitivity of PACE4 to inhibition by leupeptin and the relative
      insensitivity of PACE4 to inhibition by Ca2+ chelators and dithiothreitol; PACE4
      is not inhibited by the alpha1-antitrypsin Portland variant that is very potent
      at inhibiting furin. The unique biosynthetic and enzymic patterns seen for PACE4
      suggest a role for this neuroendocrine-specific subtilisin-like endoprotease
      outside the pathway for peptide biosynthesis.

PMID- 9032443
TI  - Role of cholesterol synthesis and esterification in the growth of CEM and MOLT4
      lymphoblastic cells.
AB  - CEM and MOLT4 are human T-cell lines isolated from patients with acute cell
      leukaemia. In culture they show important differences in cholesterol metabolism,
      CEM being less efficient at synthesizing cholesterol and having a lower activity
      of 3-hydroxy-3-methylglutaryl-CoA (HMGCoA) reductase. To investigate further the
      relationship between regulation of intracellular cholesterol metabolism at
      various steps and rate of cell growth, cholesterol synthesis, esterification and
      efflux were evaluated in CEM and MOLT4 cells at different times during
      exponential and stationary growth in vitro. It was shown that, although CEM cells
      have a lower rate of cholesterol synthesis, they grow at a faster rate than MOLT4
      cells. However, CEM cells exhibit an increased capacity to esterify cholesterol
      associated with a decreased efflux of newly synthesized cholesterol into the
      medium. These results provide evidence for an association between the capability
      to synthesize and retain cell cholesterol esters and the growth rate potential.

PMID- 9032444
TI  - Mutagenesis of charged residues in a conserved sequence in the 2-kinase domain of
      6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
AB  - Arg-136, Glu-137, Arg-138 and Arg-139 are conserved in all sequences of the 2
      kinase domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Their role
      was studied by site-directed mutagenesis. All the mutations had little, if any,
      effect on fructose-2,6-bisphosphatase activity. Mutations of Arg-136 and Glu-137
      into Ala caused only minor modifications of phosphofructo-2-kinase activity. In
      contrast, mutation of Arg138 into Ala increased 280-fold the Km for fructose 6
      phosphate of phosphofructo-2-kinase. Mutation of Arg-139 into Ala resulted in
      decreases in phosphofructo-2-kinase Vmax/Km for MgATP and fructose 6-phosphate
      600-fold and 5000-fold respectively. Mutation of Arg-139 into Lys and Gln
      increased the Km of phosphofructo-2-kinase for MgATP (20-fold and 25-fold
      respectively) and for fructose 6-phosphate (8-fold and 13-fold), and the IC50 for
      MgADP (30-fold and 50-fold) and for magnesium citrate (7-fold and 25-fold).
      However, these two mutations did not affect nucleotide binding, as measured by
      quenching of intrinsic fluorescence. The changes in kinetic properties induced by
      mutations could not be attributed to structural changes. It is proposed that Arg
      138 is involved in fructose 6-phosphate binding and that Arg-139 is probably
      involved in the stabilization of the transition state and so participates in
      catalysis.

PMID- 9032445
TI  - Modelling the 2-kinase domain of 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase on adenylate kinase.
AB  - Simultaneous multiple alignment of available sequences of the bifunctional enzyme
      6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase revealed several segments of
      conserved residues in the 2-kinase domain. The sequence of the kinase domain was
      also compared with proteins of known three-dimensional structure. No similarity
      was found between the kinase domain of 6-phosphofructo-2-kinase and 6
      phosphofructo-1-kinase. This questions the modelling of the 2-kinase domain on
      bacterial 6-phosphofructo-1-kinase that has previously been proposed [Bazan,
      Fletterick and Pilkis (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9642-9646].
      However, sequence similarities were found between the 2-kinase domain and several
      nucleotide-binding proteins, the most similar being adenylate kinase. A
      structural model of the 2-kinase domain based on adenylate kinase is proposed. It
      accommodates all the results of site-directed mutagenesis studies carried out to
      date on residues in the 2-kinase domain. It also allows residues potentially
      involved in catalysis and/or substrate binding to be predicted.

PMID- 9032446
TI  - Site-directed mutagenesis of Lys-174, Asp-179 and Asp-191 in the 2-kinase domain
      of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
AB  - In a structural model of the 2-kinase domain of the bifunctional enzyme 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase based on the analogy with
      adenylate kinase, Lys-174, Asp-179 and Asp-191 residues are located in the
      putative active site. Asp-179 and Asp-191 are conserved in all known 6
      phosphofructo-2-kinase sequences. In contrast, Lys-174 is conserved except in a
      yeast isoenzyme, fbp26, where it is replaced by glycine. Yeast fbp26 possesses
      fructose-2,6-bisphosphatase activity, but is devoid of 6-phosphofructo-2-kinase
      activity. Mutation of Asp-179 and Asp-191 of the rat liver isoenzyme to alanine
      increased the Km of 6-phosphofructo-2-kinase for fructose 6-phosphate 2000- and
      1000-fold respectively, whereas mutation of Lys-174 to glycine decreased the Vmax
      of 6-phosphofructo-2-kinase more than 4000-fold. In contrast, none of the
      mutations affected the kinetic parameters of fructose-2,6-bisphosphatase. CD and
      fluorescence measurements indicated that the mutations had no effect on the
      structure and stability of the recombinant proteins. The results show that Asp
      179 and Asp-191 participate in fructose 6-phosphate binding, whereas Lys-174 is
      important for catalysis. Therefore the natural mutation of Lys-174 to glycine in
      the fbp26 yeast isoenzyme could explain the lack of 6-phosphofructo-2-kinase
      activity. These results support a novel 6-phosphofructo-2-kinase structure model
      based on adenylate kinase.

PMID- 9032447
TI  - Glucose transport and glucose transporter GLUT4 are regulated by product(s) of
      intermediary metabolism in cardiomyocytes.
AB  - Alternative substrates of energy metabolism are thought to contribute to the
      impairment of heart and muscle glucose utilization in insulin-resistant states.
      We have investigated the acute effects of substrates in isolated rat
      cardiomyocytes. Exposure to lactate, pyruvate, propionate, acetate, palmitate,
      beta-hydroxybutyrate or alpha-oxoglutarate led to the depression of glucose
      transport by up to 50%, with lactate, pyruvate and propionate being the most
      potent agents. The percentage inhibition was greater in cardiomyocytes in which
      glucose transport was stimulated with the alpha-adrenergic agonist phenylephrine
      or with a submaximal insulin concentration than in basal or fully insulin
      stimulated cells. Cardiomyocytes from fasted or diabetic rats displayed a similar
      sensitivity to substrates as did cells from control animals. On the other hand,
      the amination product of pyruvate (alanine), as well as valine and the
      aminotransferase inhibitors cycloserine and amino-oxyacetate, stimulated glucose
      transport about 2-fold. In addition, the effect of pyruvate was counteracted by
      cycloserine. Since reversible transamination reactions are known to affect the
      pool size of the citrate cycle, the influence of substrates, amino acids and
      aminotransferase inhibitors on citrate, malate and glutamate content was
      examined. A significant negative correlation was found between alterations in
      glucose transport and the levels of citrate (P < 0.01) or malate (P < 0.01), and
      there was a positive correlation between glucose transport and glutamate levels
      (P < 0.05). In contrast, there was no correlation with changes in [1
      (14)C]pyruvate oxidation or in glucose-6-phosphate levels. Finally, pyruvate
      decreased the abundance of GLUT4 glucose transporters at the surface of
      phenylephrine- or insulin-stimulated cells by 34% and 27 % respectively, as
      determined by using the selective photoaffinity label [3H]ATB-BMPA [[3H]2-N-[4-(1
      azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis-(D-man nos-4-yloxy)propyl-2-amine]. In
      conclusion, cardiomyocyte glucose transport is subject to counter-regulation by
      alternative substrates. The glucose transport system appears to be controlled by
      (a) compound(s) of intermediary metabolism (other than glucose 6-phosphate), but
      in a different way than pyruvate dehydrogenase. Transport inhibition eventually
      occurs via a decrease in the amount of glucose transporters in the plasma
      membrane.

PMID- 9032448
TI  - Indomethacin suppresses the anti-proliferative effects of transforming growth
      factor-beta isoforms on fibroblast cell cultures.
AB  - The transforming growth factor-beta (TGFbeta) family of mediators consists of
      five closely related isoforms, of which three are present in mammals. TGFbeta1
      has been shown to exert a biphasic effect on the proliferation of several cell
      types, including fibroblasts, with stimulation at low concentrations and
      inhibition at higher concentrations. The stimulatory effects are well
      characterized, but the mechanisms by which TGFbeta1 inhibits cell proliferation
      are incompletely understood. In the present study we have compared the effects of
      all three mammalian TGFbeta isoforms on human lung fibroblast proliferation, and
      have elucidated the role of the TGFbeta-induced synthesis of prostaglandin E2
      (PGE2) in mediating their actions. All three isoforms stimulated fibroblast
      proliferation with maximal effects at 5 pg/ml (0.2 pM) and an order of potency of
      TGFbeta3 > TGFbeta2 > TGFbeta1. At higher concentrations, proliferation declined,
      and at 40 pg/ml and above all isoforms inhibited fibroblast proliferation. Again
      TGFbeta3 was the most potent, but there were no significant differences between
      the inhibitory effects of TGFbeta1 and TGFbeta2. Addition of indomethacin, an
      inhibitor of PGE2 synthesis, did not alter the proliferative activity of any of
      the TGFbeta isoforms, but completely overcame their inhibitory effects, restoring
      the stimulatory actions observed at lower TGFbeta concentrations. All TGFbeta
      isoforms stimulated PGE2 synthesis; TGFbeta3 was approximately twice as potent as
      TGFbeta1 and TGFbeta2, each of which had similar effects. These data suggest that
      the inhibition of fibroblast proliferation at higher concentrations of TGFbeta
      isoforms may be mediated by autocrine stimulation of PGE2 synthesis.

PMID- 9032449
TI  - Transcriptional regulatory elements in the upstream and intron of the fibroin
      gene bind three specific factors POU-M1, Bm Fkh and FMBP-1.
AB  - The transcriptional modulator in the fibroin gene intron is composed of multiple
      octamer-like AT-rich elements, to which several specific DNA-binding proteins
      named fibroin-modulator-binding proteins (FMBPs) bind. Three major FMBPs in the
      silk gland were characterized. Two of them (FMBP-2 and -3) were identified as a
      Fork head homologue (Bm Fkh) and a POU-domain protein (POU-M1) respectively.
      These factors were expressed in the silk gland with distinct temporal- and
      spatial-specificities during late larval development as well as during
      embryogenesis, and did not correlate directly with fibroin gene expression. The
      other (FMBP-1) appeared to correlate with the expression of the fibroin gene for
      temporal- and spatial-specificity. These FMBPs also bind to the elements in the
      upstream modulator. Transcriptional enhancement by both modulators was inhibited
      by binding competition for these factors with oligonucleotides. These results
      suggest that expression of the fibroin gene is controlled by co-ordination of
      these factors with distinct specificities during silk-gland development.

PMID- 9032450
TI  - Quality control of glycosylphosphatidylinositol anchor attachment in mammalian
      cells: a biochemical study.
AB  - hGHDAF28 is a chimaeric protein consisting of human growth hormone fused to a
      crippled signal sequence for glycosylphosphatidylinositol (GPI)-anchor addition
      from decay-accelerating factor, and serves as a model for quality control of GPI
      anchor addition. hGHDAF28 is retained in a pre-Golgi compartment and degraded
      intracellularly by a mechanism with similarity to that for other endoplasmic
      reticulum (ER)-retained proteins (Field, Moran, Lee, Keller and Caras (1994) J.
      Biol. Chem. 269, 10830-10837). We have studied the specific pathway of
      degradation for hGHDAF28 using a number of compounds which affect protein folding
      and trafficking pathways in eukaryotic cells. We found that high concentrations
      of dithiothreitol (DTT) accelerated loss of hGHDAF28 by degradation from cell
      lysates, without promoting secretion or alteration of disulphide-bond
      distribution, in contrast to a number of other examples of ER-retained proteins
      where DTT alters disulphide-bond formation. Additionally, degradation of hGHDAF28
      was sensitive to pH, being promoted at pH 6.0 and inhibited at pH 8.0; however,
      the latter effect was transient, indicating incomplete blockade. Degradation was
      also partially enhanced by depletion of ER calcium with thapsigargin, but this
      was again a partial and transient effect. Furthermore, degradation was
      temperature sensitive, with a gradual decrease in rate observed at lower
      temperatures. However, a sharp decrease in turnover between 15 degrees C and 20
      degrees C, indicative of a requirement for transport to a post-ER compartment,
      was not observed. Degradation of hGHDAF28 was insensitive to treatment with
      nocodozole or compounds preventing cytoplasmic autophagy, suggesting that ER
      degradation is independent of classical autophagy and microtubule-dependent
      processes. In addition, disruption of N-glycosylation with tunicamycin, or
      inhibition of processing of immature N-glycan chains with castanospermine or
      deoxynojirimycin, had little effect on the stability of hGHDAF28, suggesting that
      disruption of the BiP/calnexin quality-control system by bulk cellular secretory
      proteins does not influence the ER-degradation pathway of hGHDAF28.
      Intermolecular hGHDAF28 cysteine bonds result in the formation of aggregates
      which are probably important in the retention of the molecule. The insensitivity
      of this structure to reduction in vivo, together with the enhanced degradation
      rate, indicates that DTT mediates its effect on stability via a molecule involved
      in degradation of hGHDAF28, possibly a thiol-sensitive protease.

PMID- 9032451
TI  - Sheep mast cell proteinase-1: characterization as a member of a new class of dual
      specific ruminant chymases.
AB  - Sheep mast cell proteinase 1 (SMCP-1), which is abundantly expressed in
      gastrointestinal but not skin mast cells, was isolated and its substrate
      specificity was investigated. Peptide substrates, including angiotensin I,
      substance P, bradykinin and oxidized insulin B chain were hydrolysed at P1 Phe,
      Leu or Tyr residues, conforming to the known chymotrypsin-like properties of the
      enzyme. However, SMCP-1 was found to hydrolyse some chromogenic substrates with
      P1 Lys and Arg residues. The enzyme also demonstrated trypsin-like activity
      against protein substrates, cleaving BSA at Lys114-Leu115, Lys238-Val239, Lys260
      Tyr261 and Lys376-His377. Bovine fibrinogen beta-chain was cleaved at Lys28
      Lys29. To ensure homogeneity of the enzyme, the ratio of chymotrypsin-like to
      trypsin-like activity was observed; it was found to be constant during
      purification and between different preparations of SMCP-1. Treatment of SMCP-1
      with a range of inhibitors decreased chymotrypsin-like and trypsin-like
      activities by similar extents, supporting the assertion that both activities are
      the property of a single enzyme. In terms of activity, and by N-terminal amino
      acid sequencing, SMCP-1 strongly resembles the similarly dual-specific bovine
      duodenal proteinase, duodenase. It is proposed that SMCP-1 and duodenase
      represent a new class of ruminant chymases with unusual dual specificities.

PMID- 9032452
TI  - Effects of pH on phosphorylation of the Ca2+-ATPase of sarcoplasmic reticulum by
      inorganic phosphate.
AB  - The fluorescence intensity of the Ca2+-ATPase of skeletal muscle sarcoplasmic
      reticulum (SR) labelled with 4-(bromomethyl)-6,7-dimethoxycoumarin has been shown
      to decrease on phosphorylation of the ATPase with P(i), this providing a
      convenient measure of the level of phosphorylation. Comparison of the
      fluorescence decrease observed with ATP and with high concentrations of P(i) fix
      the value of the equilibrium constant for the phosphorylation reaction
      E2PMg<==>E2P(i)Mg at pH 6.0 at about 2. Studies of the pH-dependence of
      phosphorylation show that H2PO4- and HPO4(2)- bind to the ATPase with equal
      affinity, but that only binding of H2PO4- leads to phosphorylation, described by
      an equilibrium constant of 2.3. Luminal Ca2+ can bind to a pair of sites on the
      ATPase, with affinities of 1.3 x 10(3) and 1.7 x 10(3) M(-1) for the
      unphosphorylated and phosphorylated forms of the ATPase respectively, with
      stronger binding of Ca2+ to the phosphorylated form resulting in an increase in
      the effective equilibrium constant for phosphorylation.

PMID- 9032453
TI  - Rapid and transient induction of cyclo-oxygenase 2 by epidermal growth factor in
      human amnion-derived WISH cells.
AB  - The central enzyme in the prostaglandin (PG) biosynthetic cascade is PGH2
      synthase or cyclo-oxygenase (COX). At present, two distinct isoforms of PGH2
      synthase/COX have been identified: COX-1 and COX-2. In many systems, COX-1 is a
      constitutively expressed isoform that is responsible for normal physiological
      production of PGs, whereas COX-2 is an inducible isoform that responds to
      cytokines, endotoxin and growth factors by producing high levels of PGs. The
      regulation of COX-2 mRNA and protein, and the subsequent production of PGE2, were
      therefore examined in amnion-derived WISH cells stimulated with epidermal growth
      factor (EGF). Treatment of WISH cells with EGF (0.01-100 ng/ml) elicited dose
      dependent synthesis of COX-2 mRNA and protein de novo. In addition, stimulation
      of WISH cells with EGF (10 ng/ml) induced steady-state levels of COX-2 mRNA and
      protein that appeared within 30 min and then declined rapidly to near baseline
      levels within 2-4 h. In contrast, COX-1 protein was unchanged in response to
      treatment with EGF. PGE2 production was also rapid and transient. Preincubation
      of cells with the novel COX-2 enzymic inhibitor NS-398 (10(-5)-10(-10) M)
      completely prevented PGE2 formation in a dose-dependent manner. Preincubation of
      cells in dexamethasone (Dex; 0.1 microM), however, resulted in only a 31%
      decrease in PGE2 formation in response to EGF (10 ng/ml) while completely
      attenuating PGE2 biosynthesis in tumour necrosis factor alpha (TNF-alpha)
      stimulated cells. In addition, Dex (0.1 microM) was only partly effective at
      preventing EGF-induced COX-2 mRNA and protein expression de novo, whereas Dex
      completely inhibited TNF-alpha-promoted COX-2 mRNA and protein expression. Thus
      the results presented here demonstrate that EGF induces the rapid but transient
      expression of COX-2 mRNA and protein and the subsequent production of PGE2 in
      WISH cells.

PMID- 9032454
TI  - Osmoregulated taurine transport in H4IIE hepatoma cells and perfused rat liver.
AB  - The effects of aniso-osmotic exposure on taurine transport were studied in H4IIE
      rat hepatoma cells. Hyperosmotic (405 mosmol/l) exposure of H4IIE cells
      stimulated Na+-dependent taurine uptake and led to an increase in taurine
      transporter (TAUT) mRNA levels, whereas hypo-osmotic (205 mosmol/l) exposure
      diminished both taurine uptake and TAUT mRNA levels when compared with normo
      osmotic (305 mosmol/l) control incubations. Taurine uptake increased 30-40-fold
      upon raising the ambient osmolarity from 205 to 405 mosmol/l. When H4IIE cells
      and perfused livers were preloaded with taurine, hypo-osmotic cell swelling led
      to a rapid release of taurine from the cells. The taurine efflux, but not taurine
      uptake, was sensitive to 4,4'-di-isothiocyanatostilbene-2,2'-disulphonic acid
      (DIDS), suggestive of an involvement of DIDS-sensitive channels in mediating
      volume-regulatory taurine efflux. Whereas in both H4IIE rat hepatoma cells and
      primary hepatocytes TAUT mRNA levels were strongly dependent upon ambient
      osmolarity, mRNAs for other osmolyte transporters, i.e. the betaine transporter
      BGT-1 and the Na+/myo-inositol transporter SMIT, were not detectable. In line
      with this, myo-inositol uptake by H4IIE hepatoma cells was low and was not
      stimulated by hyperosmolarity. However, despite the absence of BGT-1 mRNA, a
      slight osmosensitive uptake of betaine was observed, but the rate was less than
      10% of that of taurine transport. This study identifies a constitutively
      expressed and osmosensitive TAUT in H4IIE cells and the use of taurine as a main
      osmolyte, whereas betaine and myo-inositol play little or no role in the osmolyte
      strategy in these cells. This is in contrast with rat liver macrophages, in which
      betaine has been shown to be a major osmolyte.

PMID- 9032455
TI  - Partition of the organochlorine insecticide lindane into the human sperm surface
      induces membrane depolarization and Ca2+ influx.
AB  - The effects of the insecticide lindane (the gamma-isomer of 1,2,3,4,5,6
      hexachlorocyclohexane) on membrane potential, cytosolic free Ca2+ concentration
      ([Ca2+]i) and surface biophysical properties were studied in human spermatozoa.
      The insecticide induces rapid, transient and reproducible membrane depolarization
      and opening of voltage-dependent Ca2+ channels leading to an increase in [Ca2+]i.
      In contrast with the effect in somatic cells, lindane did not affect gamma
      aminobutyric acid receptor-linked Cl- currents. Ca2+ and K+ currents were found
      to drive lindane-induced membrane depolarization and repolarization respectively,
      whereas Na+ and Cl- fluxes appear not to have a role in the phenomenon. The
      insecticide was still able to produce membrane depolarization both in the
      combined absence of extracellular Ca2+ and Na+ and in high-K+ buffer, suggesting
      that lindane alters the membrane dipole potential. In agreement with this,
      Laurodan and Prodan fluorescence spectroscopy revealed that lindane partition
      into the sperm plasma membrane lowers water molecular dynamics in the uppermost
      region of the membrane external leaflet, probably as the result of reordering of
      water dipoles. We propose that the first effect of lindane partitioning into the
      sperm plasma membrane is a change in the membrane dipole potential, which results
      in the activation of membrane-located Ca2+-influx pathways.

PMID- 9032456
TI  - The pseudoazurin gene from Thiosphaera pantotropha: analysis of upstream putative
      regulatory sequences and overexpression in Escherichia coli.
AB  - The pseudoazurin gene from Thiosphaera pantotropha has been cloned and sequenced.
      The deduced amino acid sequence showed that the protein contains an unusually
      alanine-rich signal peptide, 22 amino acid residues in length, which targets the
      protein to the periplasm. This pseudoazurin was expressed in large amounts in the
      periplasm of Escherichia coli when the gene with its native ribosome-binding site
      was placed downstream of the lac promoter. Removal of a putative hairpin-forming
      structure upstream of the ribosome-binding site increased the yield of the
      purified protein to approximately 80 mg/l. The recombinant protein is
      indistinguishable from that purified from its natural host. A primer extension
      study indicated that the pseudoazurin structural gene (pazS) is under the control
      of the Fnr/Nnr regulatory system, but no promoter-binding sequence could be
      recognized. The amino acid sequence of pseudoazurin from Paracoccus denitrificans
      is also reported.

PMID- 9032457
TI  - Effects of glucocorticoid excess on the sensitivity of glucose transport and
      metabolism to insulin in rat skeletal muscle.
AB  - GENBANK/dy examines the mechanisms of glucocorticoid-induced insulin resistance
      in rat soleus muscle. Glucocorticoid excess was induced by administration of
      dexamethasone to rats for 5 days. Dexamethasone decreased the sensitivity of 3-O
      methylglucose transport, 2-deoxyglucose phosphorylation, glycogen synthesis and
      glucose oxidation to insulin. The total content of GLUT4 glucose transporters was
      not decreased by dexamethasone; however, the increase in these transporters in
      the plasma membrane in response to insulin (100 m-units/litre) was lessened. In
      contrast, the sensitivity of lactate formation to insulin was normal. The content
      of 2-deoxyglucose in the dexamethasone-treated muscle was decreased at 100 m
      units/litre insulin, while the contents of glucose 6-phosphate and fructose 2,6
      bisphosphate were normal at all concentrations of insulin studied. The maximal
      activity of hexokinase in the soleus muscle was not affected by dexamethasone;
      however, inhibition of this enzyme by glucose 6-phosphate was decreased. These
      results suggest the following. (1) Glucocorticoid excess causes insulin
      resistance in skeletal muscle by directly inhibiting the translocation of the
      GLUT4 glucose transporters to the plasma membrane in response to insulin; since
      the activity of hexokinase is not affected, the changes in the sensitivity of
      glucose phosphorylation to insulin seen under these conditions are secondary to
      those in glucose transport. (2) The sensitivity of glycogen synthesis and glucose
      oxidation to insulin is decreased, but that of glycolysis is not affected: a
      redistribution of glucose away from the pathway of glycogen synthesis and glucose
      oxidation could maintain a normal rate of lactate formation although the rate of
      glucose transport is decreased.

PMID- 9032458
TI  - The mitochondrial carnitine carrier protein: cDNA cloning, primary structure and
      comparison with other mitochondrial transport proteins.
AB  - GENBANK/o acid sequence of the rat carnitine carrier protein, a component of the
      inner membranes of mitochondria, has been deduced from the sequences of
      overlapping cDNA clones. These clones were generated in polymerase chain
      reactions with primers and probes based on amino acid sequence information,
      obtained from the direct sequencing of internal peptides of the purified
      carnitine carrier protein from rat. The protein sequence of the carrier,
      including the initiator methionine, has a length of 301 amino acids. The mature
      protein has a modified alpha-amino group, although the nature of this
      modification and the precise position of the N-terminal residue have not been
      ascertained. Analysis of the carnitine carrier sequence shows that the protein
      contains a 3-fold repeated sequence about 100 amino acids in length. Dot plot
      comparisons and sequence alignment demonstrate that these repeated domains are
      related to each other and also to the repeats of similar length that are present
      in the other mitochondrial carrier proteins sequenced so far. The hydropathy
      analysis of the carnitine carrier supports the view that the domains are folded
      into similar structural motifs, consisting of two transmembrane alpha-helices
      joined by an extensive extramembranous hydrophilic region. Southern blotting
      experiments suggest that both the human and the rat genomes contain single genes
      for the carnitine carrier. These studies provide the primary structure of the
      mitochondrial carnitine carrier protein and allow us to identify this
      metabolically important transporter as a member of the mitochondrial carrier
      family, and the sixth of the members whose biochemical function has already been
      identified.

PMID- 9032459
TI  - Interactions of the alpha2A-adrenoceptor with multiple Gi-family G-proteins:
      studies with pertussis toxin-resistant G-protein mutants.
AB  - The alpha2A-adrenoceptor is the prototypic example of the family of G-protein
      coupled receptors which function by activation of 'Gi-like' pertussis toxin
      sensitive G-proteins. A number of members of this subfamily of G-proteins are
      often co-expressed in a single cell type. To examine the interaction of this
      receptor with individual Gi-family G-proteins the porcine alpha2A-adrenoceptor
      was transiently transfected into COS-7 cells either alone or with each of wild
      type Gi1alpha, Gi2alpha and Gi3alpha or mutations of each of these G-proteins in
      which the cysteine residue which is the target for pertussis toxin-catalysed ADP
      ribosylation was exchanged for a glycine residue. The alpha2-adrenoceptor agonist
      UK14304 stimulated both high-affinity GTPase activity and the binding of
      guanosine 5'-[gamma-35thio]-triphosphate (GTP[35S]), when expressed without any
      additional G-protein. These effects were greatly reduced by pretreatment of the
      cells with pertussis toxin. Co-expression of each of the wild-type Gi-like G
      protein alpha-subunits resulted in enhanced agonist activation of the cellular G
      protein population which was fully prevented by pretreatment with pertussis
      toxin. Co-expression of the receptor along with the cysteine-to-glycine mutations
      of Gi1alpha, Gi2alpha and Gi3alpha resulted in agonist stimulation of these G
      proteins, which was as great as that of the wild type proteins, but now the
      agonist stimulation produced over that due to the activation of endogenously
      expressed Gi-like G-proteins was resistant to pertussis toxin treatment. The Cys 
      -> Gly mutations of Gi1alpha, Gi2alpha and Gi3alpha were each also able to limit
      agonist-mediated stimulation of adenylate cyclase activity. The degree of agonist
      mediated activation of the pertussis toxin-resistant mutant of Gi1alpha was
      correlated highly both with the level of expression of this G-protein and with
      the level of expression of the alpha2A-adrenoceptor. Half-maximal stimulation of
      high-affinity GTPase activity of the Cys --> Gly mutants of Gi1alpha, Gi2alpha
      and Gi3alpha required 10-15-fold higher concentrations of agonist than did
      stimulation of their wild-type counterparts, consistent with a model in which the
      affinity of functional interactions of the alpha2A-adrenoceptor with the wild
      type G-protein is greater than with the pertussis toxin-resistant mutant G
      protein.

PMID- 9032460
TI  - Prothrombin kringle 1 domain interacts with factor Va during the assembly of
      prothrombinase complex.
AB  - The kringle 2 domain of prothrombin has been shown to interact with factor Va
      during the activation of prothrombin by the prothrombinase complex composed of
      factor Xa, factor Va, negatively charged phospholipids and Ca2+ ions. However,
      contradictory results have been reported about the role of the kringle 1 domain
      of prothrombin during the assembly of the prothrombinase complex. In an attempt
      to clarify the role of the kringle 1 domain of prothrombin, its effect on the
      activation of prothrombin by the prothrombinase complex and its direct binding to
      human factor Va were assessed. Comparative evaluation with the effects caused by
      other prothrombin structural components [a fragment 1 (gamma-carboxyglutamic acid
      and kringle 1 domains), a kringle 2 domain and a catalytic protease domain] was
      also performed. In the presence of factor Va, each kringle 1 and kringle 2
      fragment significantly inhibited the factor Xa-catalysed prothrombin activation
      in the absence of phospholipids. However, in the absence of both factor Va and
      phospholipids, kringle 2 fragment, but not kringle 1 fragment, inhibited
      prothrombin activation. Evaluation of the molecular interaction of the kringle
      domains with factor Va in assays with solid-phase phospholipid vesicles showed
      that each kringle 1 and kringle 2 fragment inhibited the prothrombinase complex
      activity. Assessment of the direct binding of prothrombin and each kringle domain
      of prothrombin with factor Va by fluorescence polarization showed that
      prothrombin, kringle 1 and kringle 2 fragments bind directly to factor Va with
      dissociation constants of 1.9+/-0.1, 2.3+/-0.1 and 2.0+/-0.4 microM (means+/
      S.D.) respectively. These findings suggest that both kringle 1 and 2 domains of
      prothrombin interact with factor Va during the assembly of the prothrombinase
      complex.

PMID- 9032461
TI  - High specificity of human secretory class II phospholipase A2 for phosphatidic
      acid.
AB  - Lysophosphatidic acid (LPA) is a potent lipid second messenger which stimulates
      platelet aggregation, cell proliferation and smooth-muscle contraction. The
      phospholipase A2 (PLA2)-catalysed hydrolysis of phosphatidic acid (PA) is thought
      to be a primary synthetic route for LPA. Of the multiple forms of PLA2 present in
      human tissues, human secretory class-II PLA2 (hs-PLA2) has been implicated in the
      production of LPA from platelets and whole blood cells challenged with
      inflammatory stimuli. To explore further the possibility that hs-PLA2 is involved
      in the production of LPA, we rigorously measured the phospholipid head group
      specificity of hs-PLA2 by a novel PLA2 kinetic system using polymerized mixed
      liposomes. Kinetic analysis of recombinant hs-PLA2 demonstrates that hs-PLA2
      strongly prefers PA as substrate over other phospholipids found in the mammalian
      plasma membrane including phosphatidylserine (PS), phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE). The order of preference is PA >> PE approximately
      PS > PC. To identify amino acid residues of hs-PLA2 that are involved in its
      unique substrate specificity, we mutated two residues, Glu-56 and Lys-69, which
      were shown to interact with the phospholipid head group in the X-ray
      crystallographic structure of the hs-PLA2-transition-state-analogue complex. The
      K69Y mutant showed selective inactivation toward PA whereas the E56K mutant
      displayed a most pronounced inactivation to PE. Thus it appears that Lys-69 is at
      least partially involved in the PA specificity of hs-PLA2 and Glu-56 in the
      distinction between PE and PC. In conjunction with a recent cell study [Fourcade,
      Simon, Viode, Rugani, Leballe, Ragab, Fournie, Sarda and Chap (1995) Cell 80, 919
      927], these studies suggest that hs-PLA2 can rapidly hydrolyse PA molecules
      exposed to the outer layer of cell-derived microvesicles and thereby produce LPA.

PMID- 9032462
TI  - One-electron oxidation pathway of peroxynitrite decomposition in human blood
      plasma: evidence for the formation of protein tryptophan-centred radicals.
AB  - Exposure of human blood plasma to peroxynitrite in the presence of 3,5-dibromo-4
      nitrosobenzenesulphonic acid (DBNBS) resulted in the trapping of a strongly
      immobilized nitroxide radical adduct. The adduct was due to protein-centred
      radicals derived not only from serum albumin but also from other major plasma
      proteins (fibrinogen, IgG, alpha1-antitrypsin and transferrin). Urate
      significantly protected plasma from the peroxynitrite-induced DBNBS-plasma
      protein adduct, whereas ascorbate and glutathione were protective at
      concentrations exceeding those usually found in plasma. Alkylation of plasma -SH
      groups did not affect the intensity of DBNBS-plasma protein adduct, whereas
      bicarbonate increased its formation, thus showing a pro-oxidant effect. The DBNBS
      plasma protein adduct provided little structural information, but subsequent non
      specific-protease treatment resulted in the detection of an isotropic three-line
      spectrum, indicating the trapping of radicals centred on a tertiary carbon. The
      nitrogen hyperfine coupling constant of this adduct and its superhyperfine
      structure were similar to those of DBNBS-tryptophan peptides with the alpha-amino
      group of tryptophan linked in the amide bond, consistent with a radical adduct
      formed at C-3 of the indole ring of tryptophan-containing peptides. DBNBS was
      unable to trap radicals derived from peroxynitrite-treated tyrosine or tyrosine
      containing peptides. Methionine treated with peroxynitrite resulted in the
      trapping of at least two DBNBS-methionine adducts with hyperfine structures
      different from that of protease-treated DBNBS-plasma proteins. These results
      demonstrate that peroxynitrite induced in blood plasma the formation of protein
      radicals centred on tryptophan residues and underline the relevance of the one
      electron oxidation pathway of peroxynitrite decomposition in biological fluids.

PMID- 9032463
TI  - Fibronectin-fragment-induced cartilage chondrolysis is associated with release of
      catabolic cytokines.
AB  - Fibronectin fragments have both catabolic and anabolic activities toward
      articular cartilage explants in vitro. Whereas a 1 nM concentration of an N
      terminal 29 kDa fibronectin fragment (Fn-f) increases the proteoglycan (PG)
      content of cartilage without induction of matrix metalloproteinases (MMPs), 0.1-1
      microM Fn-f temporarily suppresses PG synthesis and enhances MMP release. The
      higher concentrations cause an initially rapid PG depletion during the first week
      of culture, followed by much slower PG loss and gradually increasing rates of PG
      synthesis. To test for the involvement of mediators, human articular cartilage
      was cultured with Fn-f, and conditioned media were assayed for selected cytokines
      and factors. With 1 nM Fn-f, the release of the anabolic factors, insulin growth
      factor-I and transforming growth factor beta1, from cultured cartilage was
      enhanced by 50-100% during the entire 28-day culture period and this was
      associated with both supernormal rates of PG synthesis and PG content. However,
      the higher concentrations of Fn-f additionally enhanced release, by at least 10
      fold, of the cytokines, tumour necrosis factor alpha, interleukin-1alpha,
      interleukin-1beta and interleukin-6 while causing depletion of cartilage PG.
      Release of tumour necrosis factor alpha, interleukin 1beta and interleukin 1alpha
      peaked at days 2, 3 and 9 during or slightly after the period of maximal PG
      depletion and decreased to control levels by days 7, 7 and 21 respectively,
      whereas release of interleukin 6 was enhanced throughout the culture period.
      Neutralizing antibodies to the catabolic cytokines reduced Fn-f-mediated MMP-3
      release and suppression of PG synthesis. The temporal aspects of this interplay
      between catabolic and anabolic factors are consistent with the kinetics of Fn-f
      mediated cartilage damage and attempted repair and may be relevant to cartilage
      damage and repair in vivo.

PMID- 9032465
TI  - Two variants of quantitative reverse transcriptase PCR used to show differential
      expression of alpha-, beta- and gamma-fibrinogen genes in rat liver lobes.
AB  - Quantitative reverse transcriptase PCR (RT-PCR) is a sensitive method for the
      measurement of mRNA copy number. However, the methodology has gained a reputation
      for poor reproducibility, leading to concern over the validity of much of the
      data generated using this technique. We have developed two variants of
      quantitative competitive RT-PCR using a synthesized RNA as an internal standard
      to measure precisely the relative levels of alpha-, beta- and gamma-fibrinogen
      mRNAs in the four lobes of the rat liver. In the first of these variants we
      altered only the amount of total RNA in the RT-PCR reaction, keeping the amount
      of internal standard RNA and the number of PCR cycles constant. In the second
      variant only the number of PCR cycles was altered, and the amounts of total RNA
      and standard RNA were kept constant. Both variants of RT-PCR allowed calculation
      of the number of mRNA copies, which did not differ significantly between the two
      techniques. Of the two variants, the second gave better reproducibility, and the
      intra-assay coefficient of variation for this technique was 14% (n = 20). Using
      these two variants we have shown that there are different numbers of fibrinogen
      mRNAs in the four liver lobes for each of the three genes (alpha-fibrinogen F =
      14.64, P = 0.0003; beta-fibrinogen F = 3.74, P = 0.04; gamma-fibrinogen F = 3.75,
      P = 0.04). In conclusion, by using two variants of quantitative competitive RT
      PCR we have shown that this technique can be used to give reproducible results,
      and the low intra-assay coefficient of variation suggests that quantitative RT
      PCR should be the technique of choice for accurate measurement of mRNA copy
      number.

PMID- 9032464
TI  - Adrenergic stimulation of lipoprotein lipase gene expression in rat brown
      adipocytes differentiated in culture: mediation via beta3- and alpha1-adrenergic
      receptors.
AB  - In order to investigate whether the positive effect of adrenergic stimulation on
      lipoprotein lipase (LPL) gene expression in brown adipose tissue is a direct
      effect on the brown adipocytes themselves, the expression of the LPL gene was
      investigated by measuring LPL mRNA levels in brown adipocytes, isolated as
      precursors from the brown adipose tissue of rats and grown in culture in a fully
      defined medium before experimentation. Addition of noradrenaline led to an
      enhancement of LPL gene expression; the mRNA levels increased as a linear
      function of time for at least 5 h and were finally approx. 3 times higher than in
      control cells, an increase commensurate with that seen in vivo in both LPL mRNA
      levels and LPL activity during physiological stimulation. The increase was
      dependent on transcription. The effect of noradrenaline showed simple Michaelis
      Menten kinetics with an EC50 of approx. 11 nM. beta3-Agonists (BRL-37344 and CGP
      12177) could mimic the effect of noradrenaline; the beta1-agonist dobutamine and
      the beta2-agonist salbutamol could not; the alpha1-agonist cirazoline had only a
      weak effect. The effect of noradrenaline was fully inhibited by the beta
      antagonist propranolol and was halved by the alpha1-antagonist prazosin; the
      alpha2-antagonist yohimbine was without effect. An increase in LPL mRNA level
      similar to (but not significantly exceeding) that caused by noradrenaline could
      also be induced by the cAMP-elevating agents forskolin and cholera toxin, and 8
      Br-cAMP also increased LPL mRNA levels. The increase in LPL gene expression was
      not mediated via an increase in the level of an intermediary proteinaceous
      factor. It is concluded that the physiologically induced increase in LPL gene
      expression is a direct effect of noradrenaline on the brown adipocytes
      themselves, mediated via a dominant beta3-adrenergic pathway and an auxiliary
      alpha1-adrenergic pathway which converge at a regulatory point in transcriptional
      control.

PMID- 9032466
TI  - Activation of the NF-kappaB transcription factor in a T-lymphocytic cell line by
      hypochlorous acid.
AB  - Reactive oxygen species (ROS) such as hydrogen peroxide serve as second
      messengers in the induction of the transcription factor NF-kappaB, and hence in
      the activation and replication of human immunodeficiency virus type 1 (HIV-1) in
      human cells. During inflammatory reactions, many oxidative species are produced,
      one of which is hypochlorous acid (HOCl), which is responsible for the
      microbicidal effects of activated human polymorphonuclear leukocytes. Treatment
      of a T-lymphocytic cell line with micromolar concentrations of HOCl promoted the
      appearance of transcription factor NF-kappaB (the heterodimer p50/p65) in the
      nucleus of the cells, even in the absence of de novo protein synthesis. Western
      blot analysis of the NF-kappaB inhibitory subunits (IkappaB) demonstrated that
      both IkappaB-alpha proteolysis and p105 processing were induced by the treatment.
      NF-kappaB activation was very effective when cells were subjected to hyperthermia
      before being treated with HOCl. Various antioxidants, such as pyrrolidine
      dithiocarbamate, p-bromophenacyl-bromide and nordihydroguaiaretic acid could
      strongly reduce NF-kappaB translocation, demonstrating the importance of
      oxidative species in the transduction mechanism. Moreover, ACH-2 cells treated
      with HOCl or H2O2 released tumour necrosis factor-alpha (TNF-alpha) in the
      supernatants. The importance of TNF-alpha release in NF-kappaB induction by HOCl
      or H2O2 was demonstrated by the fact that: (1) the nuclear appearance of NF
      kappaB was promoted in untreated cells; and (2) synergism between TNF-alpha and
      HOCl was detected. Collectively, these results suggest that HOCl should be
      considered as an oxidative species capable of inducing NF-kappaB in a T
      lymphocytic cell line through a transduction mechanism involving ROS, and having
      a long-distance effect through subsequent TNF-alpha release.

PMID- 9032467
TI  - Influence of mutations in tissue factor on the fine specificity of macromolecular
      substrate activation.
AB  - The C-terminal fibronectin-type-III-like module of the tissue factor (TF)
      extracellular domain plays a requisite role in the activation of macromolecular
      substrates by factor VIIa (VIIa) in complex with TF. Unlike the mutations Lys165-
      >Ala, Lys166-->Ala in TF, which prevent efficient proteolysis of factor X, we
      found that the coagulant defect of a site-specific Trp158-->Arg, Ser160-->Gly
      replacement mutant of TF is largely attributable to the inability of TF to
      efficiently support the activation of the bound zymogen VII to the active
      protease VIIa. Binding studies demonstrated comparable affinity of binding of
      VIIa or VII by wild-type TF and TF(R158G160). In comparison with wild-type TF,
      the catalytic efficiency of factor X activation was reduced 56-fold with
      TF(A165A166) as the cofactor, but only 3.5-fold with TF(R165G160). The activation
      of VII bound to TF by factor Xa or VIIa was reduced 2-fold in the presence of
      TF(R158G160) and 7-8-fold with TF(A165A166). This suggests that the molecular
      recognition of VII in complex with TF by the enzymes TF-VIIa and factor Xa are
      similar. Generation of factor IXa by TF(R158G160)-VIIa was unaltered, but reduced
      2-fold with TF(A165A166). In addition, the mutations affected the cleavage of the
      two scissile bonds of factor IX differently, providing further support for the
      idea that the cofactor, TF, influences the fine specificity of activation of
      macromolecular substrates by the TF-VIIa complex.

PMID- 9032468
TI  - Differential regulation of extracellular signal-regulated protein kinase 1 and
      Jun N-terminal kinase 1 by Ca2+ and protein kinase C in endothelin-stimulated Rat
      1 cells.
AB  - The extracellular signal-regulated protein kinase (ERK) and Jun N-terminal kinase
      (JNK) signalling cascades transduce signals from the cell cytoplasm to the
      nucleus, where they regulate gene expression. The activation of ERK1 by
      lysophosphatidic acid (LPA) and endothelin 1 (Et-1) was compared in Rat-1 cells.
      Both stimulated DNA synthesis to a similar degree but, in contrast with LPA, Et-1
      did not stimulate sustained ERK1 activation, a signal that is thought to be
      important for the proliferation of fibroblasts. Et-1, but not LPA, was able to
      activate JNK1; pharmacological analysis revealed that the same EtA receptor
      mediates DNA synthesis, ERK1 and JNK1 activation. However, activation of JNK1
      required higher concentrations of Et-1 than was required for stimulation of ERK1
      or DNA synthesis. Signalling to ERK1 and JNK1 was partly inhibited by pertussis
      toxin, suggesting that both pathways are regulated in part by Gi or G0 proteins.
      Activation of JNK1 by Et-1 lagged behind ERK1 activation but was not dependent on
      it because PD98059, an inhibitor of mitogen-activated protein kinase (or ERK)
      kinase, was without effect on JNK1 activation. In contrast with recent studies,
      activation of protein kinase C (PKC) or Ca2+ fluxes inhibited activation of JNK1
      but not ERK1; furthermore inhibition of PKC or sequestration of Ca2+ potentiated
      JNK1 activation by Et-1 but not by anisomycin, and again had little effect on
      ERK1 activation. These results demonstrate that the same G-protein-coupled
      receptor can activate both the ERK and JNK signal pathways but the two kinase
      cascades seem to be separate, parallel pathways that are differentially regulated
      by PKC and Ca2+. The results are discussed in terms of the role of ERK and JNK in
      proliferative signalling.

PMID- 9032469
TI  - Differential regulation of phospholipase D and phospholipase A2 by protein kinase
      C in P388D1 macrophages.
AB  - Activation of P388D1 macrophages by phorbol myristate acetate (PMA) resulted in
      the translocation of the protein kinase C (PKC) isoforms alpha, delta, and
      epsilon from the cytosol to membranes. Furthermore, PMA activated phospholipase D
      (PLD) in these cells, and potentiated the effect of the inflammatory lipid
      mediator platelet-activating factor (PAF) on PLD activation. PAF also activated
      phospholipase A2 (PLA2) and enhanced arachidonic acid (AA) release in P388D1
      macrophages, and bacterial lipopolysaccharide (LPS) increased the responsiveness
      of these cells to PAF. In contrast with PLD, PLA2 activation in P388D1
      macrophages was found to take place independently of PKC. This was supported by
      the following evidence: (i) PMA neither induced AA release nor enhanced the PAF
      response; (ii) inclusion of PMA along with LPS during priming did not have any
      effect on PAF-stimulated AA release; (iii) down-regulation of PMA-activatable PKC
      isoforms by chronic treatment with the phorbol ester had no effect on the PAF
      response; and (iv) the PKC inhibitor staurosporine did not alter the PAF-induced
      AA release. The present study provides an example of cells in which the direct
      activation of PKC by phorbol esters does not lead to a primed and/or enhanced AA
      release. As a unique example in which PKC activation is neither necessary nor
      sufficient for AA release to occur, this now allows study of the separate and
      distinct roles for PLD and PLA2 in signal-transduction processes. This has
      hitherto been difficult to achieve because of the lack of specific inhibitors of
      these two phospholipases.

PMID- 9032470
TI  - Stimulation of Sendai virus C' protein synthesis by cycloheximide.
AB  - The polycistronic Sendai virus P/C mRNA is translated into five proteins (P, C',
      C, Y1 and Y2) from distinct start sites in virus-infected cells. The translation
      mechanism(s) of these proteins from two overlapping open reading frames in the
      P/C mRNA are poorly understood [Gupta, Ono and Xu (1996) Biochemistry 35, 1223
      1231]. While investigating the initiation mechanism of C' from an ACG start site,
      we found that C' synthesis was resistant to inhibitors of peptide chain
      elongation such as cycloheximide (CHX) and anisomycin, but not to pactamycin (an
      inhibitor of chain initiation) or puromycin (a peptide chain terminator).
      Moreover, low levels (less than 30 microg/ml) of CHX significantly stimulated C'
      synthesis. Whereas C' synthesis was stimulated, synthesis of the P and C
      proteins, which are translated from the same mRNA, decreased by more than 95%.
      Stimulation of C' synthesis by CHX is not related to its initiation at an ACG
      codon. Mutation of ACG to alternative start sites had no effect on the CHX
      stimulated C' synthesis. Similarly, C' synthesis was preferentially stimulated
      when Sendai virus-infected cells were exposed to hypotonic growth medium. These
      results suggest that the P/C mRNA may exist in at least two reversible
      conformations: whereas one conformation allows synthesis of the P and C proteins,
      the alternative conformation allows synthesis of the C' protein. It might be that
      low concentrations of CHX somehow increase the alternative conformation, which
      increases C' synthesis. The C' protein synthesis is reminiscent of the synthesis
      of stress-related proteins. Perhaps Sendai virus has evolved a novel mechanism to
      express both non-stress-related and stress-related proteins from the same mRNA.

PMID- 9032471
TI  - Identification of cell adhesive active sites in the N-terminal domain of
      thrombospondin-1.
AB  - Using a series of fusion proteins that span almost all of the thrombospondin-1
      (TSP-1) molecule, we observed in this study that Chinese hamster ovary (CHO) K1
      cells strongly attached to the N-terminus but not to the other domains of TSP-1
      (e.g. the C-terminus, and type 1, type 2 and type 3 repeats). In addition,
      attachment to the N-terminus of CHO S745 cells defective in cell-surface
      glycosaminoglycans (GAGs) was decreased by 47% compared with that observed with
      CHO K1 cells, indicating the presence of GAG-dependent cell adhesive sites. With
      the aim of identifying these cell adhesive sites, a series of synthetic peptides,
      overlapping heparin-binding sequences ARKGSGRR (residues 22-29), MKKTRG (residues
      79-84) and TRDLASIARLRIAKGVNDNF (residues 170-189), were synthesized and tested
      for their ability to support CHO cell attachment. Using both centrifugation and
      cell-attachment assays, MKKTRG-containing peptides promoted CHO K1 cell adhesion,
      while ARKGSGRR-containing peptides and peptide TRDLASIARLRIAKGVNDNF did not. CHO
      S745 cell attachment to MKKTRG-containing peptides was partially decreased. A 36%
      decrease in CHO K1 cell attachment to the N-terminus was also observed when the
      heparin-binding consensus sequence KKTR was mutated to QNTR. In addition, peptide
      MKKTRG partially inhibited (25% inhibition) CHO K1 cell attachment to the N
      terminus. However, peptide MKKTRG was not sufficient to fully promote cell
      attachment to the N-terminus of TSP-1. Peptides VDAVRTEKGFLLLASLRQ and
      TLLALERKDHS also supported CHO K1 cell attachment in a GAG-dependent and 
      independent manner respectively. Moreover, CHO K1 cell attachment to MKKTRG was
      found to be markedly enhanced when flanked with the sequences VDAVRTEKGFLLLASLRQ
      and TLLALERKDHS. Peptide VDAVRTEKGFLLLASLRQMKKTRG nearly abolished (98%
      inhibition) CHO K1 cell attachment to the N-terminus, while peptides MKKTRG,
      MKKTRGTLLALERKDHS and VDAVRTEKGFLLLASLRQ had only a moderate inhibitory effect
      (25, 27 and 53% inhibition respectively). These data indicate that the sequence
      VDAVRTEKGFLLLASLRQMKKTRGTLLALERKDHS (residues 60-94) constitutes a GAG-dependent
      cell adhesive site in the N-terminus of TSP-1. Moreover, a GAG-independent site,
      encompassing residues 189-200 (FQGVLQNVRFVF), has been identified. These two
      adhesive sites supported the attachment of a wide variety of cells (human breast
      carcinoma, melanoma and osteosarcoma cells), and a high degree of sequence
      homology was found between TSP-1 and TSP-2 between residues 60 and 94 (48%
      identity) and 189-200 (67% identity), further suggesting the functional
      importance of these two cell adhesive sites in the N-terminus of TSP-1.

PMID- 9032472
TI  - Effect of lipid composition on lipoprotein lipase activity measured by a
      continuous fluorescence assay: effect of cholesterol supports an interfacial
      surface penetration model.
AB  - The breakdown of normal substrates by lipases requires an interfacial binding
      step prior to hydrolysis. Interfacial binding and subsequent hydrolysis will be
      affected by the lipid components and hence physical properties of the substrate
      surface. In order to investigate in detail the effect of lipid structure on the
      activity of lipoprotein lipase (LPL), triolein-containing emulsion particles of
      defined composition have been used as substrates. In addition, lipase activity
      has been measured using a continuous fluorescence displacement assay that
      monitors the release of long-chain fatty acids as an alternative to normal
      radiochemical assays. Using this fluorescence assay, rates of hydrolysis of
      triolein were the same as when using a standard radiochemical assay under
      identical conditions. Activation by apolipoprotein CII was very similar by both
      methods; however, the extent of activation (2-3-fold) was less than has been
      reported previously using different assay conditions. In order to investigate the
      effect of cholesterol on LPL activity, emulsion particles were prepared in which
      the cholesterol/egg-phosphatidylcholine ratio was increased up to a 1:1 molar
      ratio. A pronounced stimulatory effect of cholesterol was observed under these
      assay conditions, with up to a 5-fold increase in rate compared with emulsion
      particles without cholesterol. Since high molar ratios of cholesterol are
      reported to exclude triacylglycerol from the phospholipid surface [Spooner and
      Small (1987) Biochemistry 26, 5820-5825], these results are not consistent with a
      mechanism involving LPL hydrolysis of surface triacylglycerol. Instead, they
      support an interfacial penetration model, allowing the enzyme's active site
      direct access to triacylglycerol in the lipoprotein core. Perturbation of the
      surface phospholipid monolayer of the emulsion particle as a result of hydrolysis
      by Naja naja phospholipase A2 resulted in a 10-fold activation of LPL, providing
      further support for an interfacial penetration model. The stimulatory effect of
      apolipoprotein CII was not modulated by modification of the interface with
      cholesterol.

PMID- 9032473
TI  - Accumulation of glucosaminyl(acyl)phosphatidylinositol in an S3 HeLa subline
      expressing normal dolicholphosphomannose synthase activity.
AB  - Glucosaminyl(acyl)phosphatidylinositol [GlcN(acyl)PI], the third intermediate in
      the mammalian glycosylphosphatidylinositol (GPI) anchor pathway, is undetectable
      in most cells. This intermediate was previously shown to accumulate, however, in
      murine lymphoma mutant E and in yeast mutant dpm1, both of which lack
      dolicholphosphomannose synthase activity. Here we report that a mammalian HeLa S3
      subline, denoted D, produces large amounts of GlcN(acyl)PI. The level of
      GlcN(acyl)PI in this subline is twice that in the murine lymphoma mutant E and 4
      times that in the parental S3 line. This HeLa D subline differs from the
      previously reported mutants that accumulate GlcN(acyl)PI because no defects in
      the synthesis or utilization of dolicholphosphomannose were found. Kinetic
      analysis indicated that in this HeLa subline there is an increased rate of
      synthesis of GlcN(acyl)PI, whereas the rate of metabolism for this GPI is
      comparable to that in wild-type cells. Furthermore, HeLa D cells accumulate
      GlcN(acyl)PI without a block in the synthesis of the downstream mannosylated GPI
      anchor precursors and GPI-anchored proteins. These findings might be relevant for
      understanding the regulation of the GPI pathway.

PMID- 9032474
TI  - Electrical stimulation of C2C12 myotubes induces contractions and represses
      thyroid-hormone-dependent transcription of the fast-type sarcoplasmic-reticulum
      Ca2+-ATPase gene.
AB  - Chronic low-frequency contraction of skeletal muscle, either induced by a slow
      motor nerve or through direct electrical stimulation, generally induces
      expression of proteins associated with the slow phenotype, while repressing the
      corresponding fast isoforms. Contractions thereby counteract the primarily
      transcriptional effect of thyroid hormone (T3) which results in the selective
      induction and stimulation of expression of fast isoforms. We studied the
      regulation of expression of the fast-type sarcoplasmic-reticulum Ca2+-ATPase
      (SERCA1), a characteristic component of the fast phenotype. Previous work
      suggested that reduction of SERCA1 expression by contractile activity might
      result from interference with the T3-dependent transcriptional stimulation of the
      SERCA1 gene. The present study was set up to test this unexpected mode of action
      of contractile activity. We show that electrical stimulation of C2C12 mouse
      myotubes, which results in synchronous contractions at the imposed frequency,
      reduces basal but virtually abolishes T3-dependent SERCA1 expression. T3
      dependent expression of a reporter gene driven by the SERCA1 promoter was
      similarly affected by electrical stimulation. This is the first demonstration
      that the counteracting effects on muscle gene expression of electrically induced
      contractions and T3 may interact at the transcriptional level.

PMID- 9032475
TI  - Molecular cloning and biochemical characterization of a Drosophila
      phosphatidylinositol-specific phosphoinositide 3-kinase.
AB  - Molecular, biochemical and genetic characterization of phosphoinositide 3-kinases
      (PI3Ks) have identified distinct classes of enzymes involved in processes
      mediated by activation of cell-surface receptors and in constitutive
      intracellular protein trafficking events. The latter process appears to involve a
      PtdIns-specific PI3K first described in yeast as a mutant, vps34, defective in
      the sorting of newly synthesized proteins from the Golgi to the vacuole. We have
      identified a representative member of each class of PI3Ks in Drosophila using a
      PCR-based approach. In the present paper we describe the molecular cloning of a
      PI3K from Drosophila, P13K_59F, that shows sequence similarity to Vps34. PI3K_59F
      encodes a protein of 108 kDa co-linear with Vps34 homologues, and with three
      regions of sequence similarity to other PI3Ks. Biochemical characterization of
      the enzyme, by expression of the complete coding sequence as a glutathione S
      transferase fusion protein in Sf9 cells, demonstrates that PI3K_59F is a PtdIns
      specific PI3K that can utilize either Mg2+ or Mn2+. This activity is sensitive to
      inhibition both by non-ionic detergent (Nonidet P40) and by wortmannin (IC50 10
      nM). PI3K_59F, therefore, conserves both the structural and biochemical
      properties of the Vps34 class of enzymes.

PMID- 9032476
TI  - Interaction of human CYP17 (P-450(17alpha), 17alpha-hydroxylase-17,20-lyase) with
      cytochrome b5: importance of the orientation of the hydrophobic domain of
      cytochrome b5.
AB  - Human CYP17 (P-450(17alpha), 17alpha-hydroxylase-17,20-lyase)-catalysed side
      chain cleavage of 17alpha-hydroxyprogestogens into androgens is greatly dependent
      on the presence of cytochrome b5. The native form of cytochrome b5 is composed of
      a globular core, residues 1-98, followed by a membrane insertable C-terminal
      tail, residues 99-133. In the present study the abilities of five different forms
      of cytochrome b5 to support the side-chain cleavage activity of CYP17 were
      compared. The five derivatives were: the native pig cytochrome b5 (native pig),
      its genetically engineered rat counterpart (core-tail), the soluble core form of
      the latter (core), the core with the secretory signal sequence of alkaline
      phosphatase appended to its N-terminal (signal-core) and the latter containing
      the C-terminal tail of the native rat protein (signal-core-tail). When examined
      by Edman degradation and MS, the engineered proteins were shown to have the
      expected N-terminal amino acid sequences and molecular masses. The native pig was
      found to be acetylated at the N-terminal. The native pig and core-tail enzymes
      were equally efficient at enhancing the side-chain cleavage activity of human
      CYP17 and the signal-core-tail was 55% as efficient. The core and signal-core
      constructs were completely inactive in the aforementioned reaction. All the five
      derivatives were reduced to varying degrees by NADPH:cytochrome P-450 (NADPH
      P450) reductase and the relative efficiencies of this reduction were reminiscent
      of the behaviour of these derivatives in supporting the side-chain cleavage
      reaction. In the side-chain cleavage assay, however, NADPH-P450 reductase was
      used in large excess so that the reduction of cytochrome b5 derivatives was not
      rate-limiting. The results highlight that productive interaction between
      cytochrome b5 and CYP17 is governed not only by the presence of a membrane
      insertable hydrophobic region on the cytochrome b5 but also by its defined
      spatial orientation at the C-terminal.

PMID- 9032477
TI  - Identification of a receptor-type protein tyrosine phosphatase expressed in
      postmitotic maturing neurons: its structure and expression in the central nervous
      system.
AB  - We have isolated a rat cDNA encoding a receptor-type protein-tyrosine-phosphatase
      (RTP) expressed in brain and kidney (RPTP-BK) and characterized its expression in
      the developing central nervous system. RPTP-BK has seven fibronectin type III
      like repeats in the extracellular region and a unique catalytic phosphatase
      domain in the cytoplasmic region. Bacterial expression of its phosphatase domain
      showed that the dephosphorylation of phosphotyrosine residues was mediated by the
      cytoplasmic catalytic domain. Sequence comparison revealed that RPTP-BK is
      homologous with GLEPP1, a rabbit PTP expressed in renal glomerular epithelia, and
      has the same phosphatase domain as murine PTPphi expressed in macrophages. RPTP
      BK has also significant homology with Drosophila DPTP10D in the phosphatase
      domain, whose expression is localized exclusively in growth cones of the
      embryonal brains. The gene for RPTP-BK is well conserved among other species, and
      the expression in the brain but not in the kidney is developmentally regulated
      during the neonatal stage. Hybridization in situ showed that RPTP-BK is highly
      expressed in the postmitotic maturing neurons of the olfactory bulb, developing
      neocortex, hippocampus and thalamus. Because the expression of RPTP-BK in the
      developing neocortex is correlated with the stage of axonogenesis in cortical
      neurons, RPTP-BK might be crucial in neural cell development of the mammalian
      central nervous system.

PMID- 9032479
TI  - Structural analysis of the oligosaccharide-alditols released by reductive beta
      elimination from the jelly coat of Rana utricularia eggs.
AB  - The O-linked oligosaccharides of the jelly coat surrounding the eggs of Rana
      utricularia were analysed by 1H-NMR spectroscopy. Comparison of their structures
      with those characterized from seven other amphibians confirms that the
      carbohydrate chains of the jelly coat mucins are markers of the species. The new
      sequence GlcNAc(beta1-3)GlcNAc(beta1-6)[Gal(beta1-3)]GalNAc-ol is characteristic
      of Rana utricularia. The presence of blood group A determinants constitutes the
      main feature of this mucin.

PMID- 9032478
TI  - Utilization of troponin C as a model calcium-binding protein for mapping of the
      calmodulin-binding sites of caldesmon.
AB  - Troponin C, a structural analogue of calmodulin, was used for mapping the
      calmodulin-binding sites of caldesmon. The apparent Kd values for the formation
      of the caldesmon-calcium-binding-protein complex as determined by native gel
      electrophoresis were 0.5, 1.2 and 3.9 microM for calmodulin, rabbit skeletal
      muscle troponin C and bovine cardiac troponin C respectively. Troponin C induced
      a 4-6 nm blue shift of the Trp fluorescence of caldesmon without affecting the
      amplitude of fluorescence. In the presence of Ca2+, troponin C induced partial
      displacement of caldesmon from actin tropomyosin complexes. Addition of 5,5'
      dithiobis(nitrobenzoic) acid to an equimolar complex of caldesmon and troponin C
      induced disulphide cross-linking between Cys-98 of rabbit skeletal muscle
      troponin C and the single Cys residue of duck gizzard caldesmon, located in a
      position analogous to Cys-580 of the chicken gizzard protein. The cross-linked
      caldesmon-troponin C complex was ineffective in inhibiting actomyosin ATPase
      activity. It is concluded that Cys-580 of caldesmon can be located close to both
      the central helix of calcium-binding proteins and the C-terminal domain of actin.
      This may be important for the regulation of actomyosin ATPase activity by
      caldesmon.

PMID- 9032480
TI  - Biochemical analysis of a bladder-cancer-associated mucin: structural features
      and epitope characterization.
AB  - Three monoclonal antibodies (mAbs), M344, M300 and M75, were shown to define a
      unique tumour-associated antigen (TAA) of superficial bladder tumours. The
      antigenic determinants are expressed on a very-high-molecular-mass component and,
      in about 50% of the positive samples, one determinant is also detected on a 62
      kDa molecular species, observed only under reducing conditions. The objectives of
      the present study were to characterize further this TAA by analysing (1) the
      biochemical nature of the epitopes recognized by the three mAbs, and (2) the
      biochemical and structural features of the molecule bearing them. The
      antigenicity was resistant to heat denaturation, trypsin and alpha-chymotrypsin
      treatments but highly sensitive to papain and Pronase digestion. NaIO4 oxidation
      decreased reactivity to mAbs M344 and M300 but enhanced reactivity to mAb M75.
      The three determinants were insensitive to beta-galactosidase and alpha-L
      fucosidase but were sensitive to Vibrio cholerae neuraminidase. None of the three
      mAbs reacted with ovine, bovine or porcine submaxillary mucins. Deglycosylation
      with O-glycosidase or trifluoromethanesulphonic acid completely abolished the
      reactivity of the mAbs whereas N-glycosidase F deglycosylation had no appreciable
      effect. The presence on the molecule of cryptic Gal(beta(1-3))GalNAc as a major
      core disaccharide was demonstrated by a heterologous sandwich assay using mAb M75
      and peanut agglutinin. Thiol reduction using beta-mercaptoethanol increased
      mobility of the high-molecular-mass component in polyacrylamide gels. We thus
      conclude that mAbs M344 and M300 react with sialylated carbohydrate epitopes, and
      mAb M75 reacts with a partially cryptic and periodate-resistant sialylated
      epitope expressed on a typical secreted high-molecular-mass oligomeric mucin
      which we named MAUB for mucin antigen of the urinary bladder.

PMID- 9032481
TI  - Nitric oxide co-operates with hydrogen peroxide in inducing DNA fragmentation and
      cell lysis in murine lymphoma cells.
AB  - We examined whether NO and H2O2 could interact in inducing DNA fragmentation and
      cell death. H2O2 and the NO-releasing compounds sodium nitroprusside (SNP) and S
      nitroso-N-acetyl-D,L-penicillamine (SNAP) by themselves elicited lysis of YAC-1
      murine lymphoma cells in a concentration-dependent manner. Exposure of the cells
      to a combination of sublytic concentrations of SNP (0.78 mM) plus H2O2 (7.8
      microM) or SNAP (0.18 mM) plus H2O2 (7.8 microM) resulted in cell death which is
      mediated, in part, through apoptosis. Evidence for this direction is provided by
      fluorescence microscopic evaluation of the cells, which revealed the presence of
      changes in nuclear morphology characteristic of apoptosis in 30-40% of lymphoma
      cells and by the specific pattern of internucleosomal DNA fragmentation detected
      by gel electrophoresis. The cytotoxic effect of SNP plus H2O2 could be
      effectively inhibited by either oxyhaemoglobin, which binds NO, or catalase,
      which eliminates H2O2. Partial protection from SNP-plus-H2O2-induced cell lysis
      was observed with the poly(ADP-ribose) polymerase inhibitors, nicotinamide and 3
      aminobenzamide, parallelling their ability to reverse depletion of cellular NAD+
      pools. These results indicate an interaction between NO and H2O2 which leads to a
      markedly enhanced cytotoxic activity, in part, via induction of apoptosis and
      suggest that poly(ADP-ribosylation) and subsequent NAD+ depletion mediate, at
      least in part, this cytotoxic activity.

PMID- 9032482
TI  - The pleura: the outer space of pulmonary medicine.

PMID- 9032483
TI  - Nitric oxide and microvascular permeability: a continuing dilemma.

PMID- 9032484
TI  - Dietary fat and asthma: is there a connection?
AB  - The last two decades have seen an increase in the prevalence of asthma, eczema,
      and allergic rhinitis in developed countries. This increase has been paralleled
      by a fall in the consumption of saturated fat and an increase in the amount of
      polyunsaturated fat in the diet. This is due to a reduction in the consumption of
      animal fat and an increase in the use of margarine and vegetable oils containing
      omega-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid. There is also
      evidence for a decrease in the consumption of oily fish which contain omega-3
      PUFAs, such as eicosapentaenoic acid. In a number of countries, there are social
      class and regional differences in the prevalence of allergic disease, which are
      associated with differences in the consumption of PUFAs. Linoleic acid is a
      precursor of arachidonic acid, which can be converted to prostaglandin E2 (PGE2),
      whereas eicosapentaenoic acid inhibits the formation of PGE2. PGE2 acts on T
      lymphocytes to reduce the formation of interferon-gamma (IFN-gamma) without
      affecting the formation of interleukin-4 (IL-4). This may lead to the development
      of allergic sensitization, since IL-4 promotes the synthesis of immunoglobulin E
      (IgE), whereas IFN-gamma has the opposite effect. Changes in the diet may explain
      the increase in the prevalence of asthma, eczema and allergic rhinitis. The
      effects of diet may be mediated through an increase in the synthesis of
      prostaglandin E2 which in turn can promote the formation of immunoglobulin E.

PMID- 9032485
TI  - Role of endogenous nitric oxide in airway microvascular leakage induced by
      inflammatory mediators.
AB  - This study examines the role of endogenous nitric oxide (NO) in airway
      microvascular leakage induced inflammatory mediators, which play an important
      role in asthmatic airways. Guinea-pigs were anesthetized and mechanically
      ventilated with monitoring of arterial blood pressure, and airway microvascular
      leakage induced by intravenous injection of substance P (SP), leukotriene D4
      (LTD4) and histamine was evaluated using Evans blue dye and Monastral blue dye in
      the presence and absence of the NO synthase inhibitors, L-NG-nitroarginine methyl
      ester (L-NAME) and L-NG-monomethyl arginine (L-NMMA). The effect of a soluble
      guanylate cyclase inhibitor, LY83583, on SP-induced dye leakage was also
      examined. Intravenous injection of SP (1 microgram.kg-1), LTD4 (1 microgram.kg-1)
      and histamine (100 micrograms.kg-1) significantly increased dye extravasation at
      all airway levels. Pretreatment with L-NAME (10 mg.kg-1 i.v.) and L-NMMA (100
      mg.kg-1 i.v.) significantly inhibited SP-induced extravasation, and L-arginine
      (100 mg.kg-1 i.v.) reversed L-NAME-induced inhibition. L-NAME (10 mg.kg-1 i.v.)
      also significantly inhibited LTD4-induced dye extravasation only in central
      airways, and this inhibitory effect was abolished by a neurokinin-1 (NK1)
      antagonist, FK888 (10 mg.kg-1 i.v.) pretreatment. Histamine-induced dye
      extravasation was not affected by L-NAME. LY83583 (2.5 and 7.5 mg.kg-1 i.v.)
      partially but significantly reduced SP-induced dye leakage. These results suggest
      that endogenous nitric oxide plays a role in neurokinin-1 receptor-mediated
      airway microvascular leakage, and presumably involves the guanylate cyclase
      pathway.

PMID- 9032486
TI  - Persistence of respiratory syncytial virus (RSV) infection and development of RSV
      specific IgG1 response in a guinea-pig model of acute bronchiolitis.
AB  - Acute respiratory syncytial virus (RSV) bronchiolitis in children can result in
      sequelae of recurrent wheezing and asthma and production of RSV-specific
      immunoglobulin E (IgE), but the pathogenesis of these sequeleae is poorly
      understood. Guinea-pigs experimentally inoculated with human RSV show
      histological evidence of acute bronchiolitis and chronic persistence of viral
      antigens and genome in the lungs; whether this persistence is due to infectious
      replicating virus, and whether infected animals develop RSV-specific
      immunoglobulin G1 (IgG1) (the main class of antibody involved in guinea-pig
      allergic responses) is unknown. Guinea-pigs were inoculated intranasally with
      human RSV or with uninfected cell culture supernatant. At times ranging 1-60 days
      postinoculation, the viral titre in the lung was determined by immunoplaque assay
      (a method combining viral culture and immunocytochemistry). Serum titres of RSV
      specific IgG1 antibodies were determined by enzyme-linked immunosorbent assay.
      Bronchiolar inflammation was assessed on coded lung sections, by using a
      semiquantitative, histological scoring system based on features of human acute
      bronchiolitis. Infectious RSV was cultured from the lungs of infected animals on
      all study days, with maximal viral replication observed on Day 3. RSV-specific
      IgG1 antibodies were detected in all RSV-inoculated animals from Day 7 onward,
      with the highest antibody titre measured on Day 28. RSV-inoculated guinea-pigs
      had maximal bronchiolar inflammation on Day 7, and had significantly increased
      polymorphonuclear cell infiltrates on Days 28 and 60. Respiratory syncytial virus
      chronically persists as infectious virus in the guinea-pig lung. Infected animals
      develop an anti-respiratory syncytial virus immunoglobulin G1 antibody response,
      histological evidence of acute bronchiolitis, and chronic airway inflammation.
      Persistent respiratory syncytial virus lung infection may be important in the
      pathogenesis of postbronchiolitis wheezing and asthma in children.

PMID- 9032487
TI  - Bronchial compliance and wall structure during development of the immature human
      and pig lung.
AB  - Maturational changes in the specific compliance could potentially contribute to
      the development or clinical presentation of respiratory diseases in infants and
      children. Changes in the specific compliance during development and its
      structural basis have been well characterized, but changes in bronchial
      compliance and the mechanisms involved have received little attention. Semistatic
      pressure-volume curves were generated for isolated bronchial segments from late
      term foetal, immature and adult pigs. A small number of bronchi from human
      infants were also studied. The amount of cartilage in the bronchial wall of pigs
      of different ages was measured histologically, and morphometric changes in the
      wall of inflated bronchi were investigated. The specific compliance of bronchi
      approximately halved from 1 to 4 weeks of age. No change in specific compliance
      was observed either between 4 week old and adult pigs, or between late-term
      foetal and 1 week old pigs. Changes in the total wall and cartilage areas did not
      correlate with changes in specific compliance. Inflation to 20 cmH2O transmural
      pressure reduced the total wall area of bronchi from 1 week old pigs. Significant
      changes in bronchial distensibility occur during the early postnatal period.
      These changes in specific compliance are not caused by an increase in the amount
      of cartilage. The increase in luminal volume during inflation of bronchial
      segments occurs, partially, by compression of the airway wall against the
      cartilage layer.

PMID- 9032488
TI  - Nasal mucociliary transport is impaired at altitude.
AB  - There have been a number of anecdotal reports of rhinitis and nasal obstruction
      occurring at altitude. To quantify these reports, we investigated nasal
      obstruction and mucociliary transport in a group of healthy volunteers trekking
      to Mount Everest Base Camp, Nepal, altitude 5,300 m. Nasal obstruction was
      estimated by subjective scoring and mucociliary transport was determined by the
      saccharin method. Subjective assessment showed that nasal obstruction was
      increased on arrival at 5,300 m in 23 out of 54 subjects, unchanged in 24, and
      decreased in seven (McNemar's test: chi 2 = 7.5; p < 0.01). The median saccharin
      time at sea level was 11 min (95% confidence interval (95% CI) 8-17 min) and
      increased to 60 min (95% CI 27-60 min) on arrival at 5,300 m. Compared to sea
      level, the saccharin time was prolonged in 25 out of 33 subjects (McNemar's test:
      chi 2 = 14.7; p < 0.01), and remained prolonged after 2 weeks at altitude (median
      60 min; 95% CI 38-60 min). These results confirm the subjective feelings of nasal
      obstruction and show that nasal mucociliary transport times are increased at
      altitude. The mechanisms of these findings are not clear, but nasal obstruction
      may impede breathing and adversely affect performance at altitude.

PMID- 9032489
TI  - Mast cell tryptase potentiates histamine-induced contraction in human sensitized
      bronchus.
AB  - The mast cell plays a pivotal role in the early asthmatic response via release of
      mediators, which directly influence airway smooth muscle tone. Canine mast cell
      tryptase has been reported to potentiate the contractile response of canine
      isolated airways to histamine. The aim of this study was to investigate whether
      human mast cell tryptase potentiated contractile responses in human isolated
      bronchi. The effect of tryptase differed according to the sensitization status of
      the bronchi. In lung tissue from sensitized patients (those whose bronchial
      tissue contracted in response to the application of any of four common antigens)
      90 ng.mL-1 of human purified lung tryptase markedly potentiated the contractile
      response to histamine. The maximal response as a percentage of maximal
      contraction to acetylcholine was 80 +/- 8% in control tissues and 119 +/- 6% in
      tryptase treated tissues (n = 4; p < 0.05). Tryptase, at a dose of 200 ng.mL-1,
      also potentiated responses but to a lesser degree, 100 +/- 5% (n = 4; p < 0.05).
      In nonsensitized bronchi, neither 90 nor 200 ng.mL-1 tryptase had any significant
      effect on histamine responses. The increased response in the presence of tryptase
      in sensitized tissue was inhibited by the calcium voltage-dependent channel
      antagonist, verapamil (10(-6) M). We have shown, for the first time, that human
      mast cell tryptase potentiates contraction in sensitized bronchi via a calcium
      related mechanism. These findings provide a link between a mast cell derived
      product and in vitro human airway hyperresponsiveness.

PMID- 9032490
TI  - Asymptomatic bronchial hyperresponsiveness in adolescents and young adults.
AB  - The clinical significance of asymptomatic bronchial hyperresponsiveness (BHR) is
      not well-known. The aim of this study was to explore, in a cross-sectional
      analysis, the characteristics of adolescent subjects with asymptomatic BHR, as
      compared to nonhyperresponsive subjects and those with symptomatic BHR. The
      subjects were selected by date of birth from the register of general
      practitioners. The hypothesis that both asymptomatic and symptomatic BHR are
      related to early childhood lower respiratory tract infections was also tested, in
      a historical cohort analysis. Respiratory morbidity was studied in early
      childhood and BHR in adolescence and young adulthood, in a population of 551
      subjects aged 10-23 yrs. Morbidity had been recorded prospectively since birth in
      the general practice. Data on chronic respiratory symptoms, smoking behaviour,
      airways obstruction, BHR and allergy were collected during this investigation.
      BHR was present in 42% of the subjects, of which 70% were asymptomatic. The
      occurrence of symptomatic BHR was related to acute bronchitis in early childhood,
      allergy, airways obstruction and recent asthma, acute bronchitis and hay fever;
      whereas, asymptomatic BHR was not. Characteristics of subjects with asymptomatic
      BHR did not differ significantly from those without BHR, with respect to these
      factors. We conclude that asymptomatic bronchial hyperresponsiveness in
      adolescence and young adulthood is not related to lower respiratory infections in
      early childhood. Furthermore, subjects with asymptomatic bronchial
      hyperresponsiveness have similar characteristics to those without bronchial
      hyperresponsiveness, but differ strongly from subjects with symptomatic
      hyperresponsiveness. Asymptomatic bronchial hyperresponsiveness may not be the
      link between early childhood lower respiratory morbidity and asthma in later
      life, nor a risk factor for later asthma.

PMID- 9032491
TI  - Comparison of reported prevalences of recent asthma in longitudinal and cross
      sectional studies.
AB  - A potential source of bias in prevalence rates reported for symptoms and
      diagnoses of asthma in longitudinal studies could arise if repeated questioning
      of subjects or previous experience of lung function and airway responsiveness
      tests increased awareness of respiratory symptoms. We wished to determine the
      extent of any such bias by comparing reported prevalence rates from a
      longitudinal and cross-sectional study within similar populations. The
      prevalences of wheezing in the last year, waking with chest tightness, waking
      with shortness of breath, waking with coughing, having an attack of asthma in the
      last year, and current use of medications for asthma were determined using
      identical questions in two populations. Self-completed questionnaire responses of
      946 subjects, 21 yrs of age, participating in the seventh respiratory assessment
      in the longitudinal Dunedin Multidisciplinary Health and Development Research
      Study were compared with responses provided by 991 subjects, aged 20-22 yrs,
      completing a postal questionnaire on one occasion only for the New Zealand
      section of the European Community Respiratory Health Study. The prevalence rates
      were not significantly different between the two populations, for all of the
      reported symptoms and for medication use. Differences in responses between
      genders were similar in each study, with all responses being more common in
      females. We conclude that repeated questioning regarding respiratory symptoms and
      repeated lung function and bronchial challenge testing in a longitudinal study of
      asthma did not bias prevalence rates compared with those obtained in a similar
      population of the same age studied on only one occasion.

PMID- 9032492
TI  - Consequences of occupational asthma on employment and financial status: a follow
      up study.
AB  - The aim of this study was to describe changes in employment and income following
      a diagnosis of occupational asthma, and to determine what factors might affect
      these changes. Two hundred and nine patients with occupational asthma were
      reviewed on average 3.1 yrs after the diagnosis had been made. They were
      contacted by telephone or were sent a self-administered questionnaire by post.
      Multiple logistic regression models were constructed to determine which variables
      were associated with loss of employment after the diagnosis. At the time of
      review, 44% of patients had left their previous job and 25% were currently
      unemployed. Remarkably, 32% remained exposed to the offending agents in the same
      job. Forty six percent of the patients had suffered a reduction of income (84% of
      those who had left their employer versus 19% of those still employed in the same
      company (p < 0.001)). Claims for compensation, size of the company, level of
      education, and age at the time of diagnosis were significantly associated with a
      risk for becoming unemployed or having a new employer after the diagnosis of
      occupational asthma. Occupational asthma results in severe socioeconomic
      consequences. The French compensation system for occupational asthma should be
      revised, as the criteria currently used to determine compensation for this
      disease largely underestimate the social and occupational damages.

PMID- 9032493
TI  - Size and strength of the respiratory and quadriceps muscles in patients with
      chronic asthma.
AB  - There have been few studies of respiratory and limb muscle size and function in
      middle-aged patients with asthma and persistent airways obstruction. We have
      compared the forces generated by the respiratory and thigh muscles with their
      dimensions assessed by ultrasound in nine middle-aged patients with chronic
      asthma (mean age 56 (SD 8) yrs; functional residual capacity/total lung capacity
      ratio (FRC/TLC) 60 (10)%), and in nine normal subjects (aged 53 (7) yrs; FRC/TLC
      55 (5)%). Diaphragm thickness was measured at the zone of apposition by B-mode
      ultrasound during relaxation (DiTrelax) and during a maximum-effort inspiratory
      manoeuvre (DiTpI,max) at FRC. Cross-sectional area of the relaxed rectus femoris
      muscle (ARF) was determined by ultrasound at mid-thigh level. Isometric strength
      of the right quadriceps muscle group was measured during maximum voluntary
      contraction. Asthmatic patients had preserved quadriceps strength and ARF but
      moderately impaired maximum inspiratory pressure (PI,max) (-52 (18) cmH2O) and
      thicker DiTrelax (2.2 (0.4) mm), compared to normal subjects (-73 (21) cmH2O and
      1.7 (0.3) mm, respectively). Middle-aged patients with chronic asthma and a small
      increase in functional residual capacity/total lung capacity ratio have preserved
      limb muscle force and dimensions, modestly impaired inspiratory muscle strength,
      and slightly increased thickness of the costal diaphragm. Future studies of
      respiratory muscle function in asthma should be aided by measurement of diaphragm
      thickness and of limb muscle strength and size. Such studies are required
      particularly in older patients with severe hyperinflation who are most likely to
      have impairment of muscle function.

PMID- 9032494
TI  - Does ketotifen have a steroid-sparing effect in childhood asthma?
AB  - In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a
      study was performed to determine whether ketotifen (versus placebo) can replace
      or allow a reduction in the dose of ICS required for the maintenance treatment of
      childhood asthma. Sixty six children (aged 6-13 yrs) with asthma (confirmed by
      methacholine challenge), who were maintained on ICS, at a dose of < or = 1 mg.day
      1, were selected, and 52 subjects completed the trial. Children on long-term oral
      steroids or cromoglycate were excluded. After a 4 week baseline period, the
      children were randomized to receive ketotifen, 2 mg.day-1, or placebo for 32
      Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by
      25% every second week to the minimum dose tolerated by the patients. For the
      remainder of the study (Weeks 21-32) the patients continued on this dose (if
      tolerated). Beta 2-agonists were allowed, as necessary, for symptom relief.
      During the baseline period, the mean daily ICS dosage was 432 micrograms in the
      ketotifen group versus 408 micrograms in the placebo group (NS). Among the
      patients who completed the study, the average ICS dosage during the final phase
      of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus
      35% in the placebo group (NS). Lung function, diurnal variability in peak flow
      rates and methacholine sensitivity (provocative concentration producing a 20%
      fall in forced expiratory volume in one second (PC20)) remained unchanged in both
      groups throughout the study. During the last 12 weeks of the study, the ketotifen
      treated patients were symptomatically better controlled. In the present study,
      ketotifen did not have a greater steroid-sparing effect than placebo.

PMID- 9032495
TI  - Effect of influenza A virus infection on acid-induced cough response in children
      with asthma.
AB  - Although it is well-known that some types of respiratory viral infections cause
      airway hyperresponsiveness in humans, the effect of viral infection on the cough
      threshold in asthmatics is not known. We, therefore, evaluated the effects of
      naturally-acquired influenza A virus infection on the cough threshold to inhaled
      acid in children with asthma. Twelve children with asthma (9 boys and 3 girls,
      mean +/- SEM age of 10.8 +/- 0.6 yrs), who had naturally-acquired influenza A
      virus infection in winter (January-February, 1992) during an epidemic of
      influenza A (H1N1), were enrolled in this prospective, uncontrolled study. All
      patients underwent acetic acid (AA) inhalation challenge 2, 4 and 6 weeks after
      the influenza infection. The cough threshold values (the lowest concentrations of
      AA eliciting coughs) after 2, 4 and 6 weeks of the illness were 3.7 +/- 0.9, 5.3
      +/- 1.0 and 8.1 +/- 1.4% (mean +/- SEM), respectively. Cough threshold values 4
      or 6 weeks after the illness improved significantly over that at 2 weeks (p <
      0.05 and p < 0.01, respectively). In contrast, baseline forced expiratory volume
      in one second did not change throughout the study. These results indicate that
      influenza A virus infection attenuates the cough threshold independently of
      airway obstruction in children with asthma. The enhanced cough response following
      virus infection is probably mediated by damage to the airways epithelium.

PMID- 9032496
TI  - Oscillatory pressure transients after flow interruption during bronchial
      challenge test in children.
AB  - The measurement of the conventional interrupter resistance (Rint) is dependent on
      pressure equilibration between alveolar and airway opening pressure, which is
      often not achieved in the presence of severe airways obstruction or in small
      children. The damping properties (d) of postocclusional oscillatory pressure
      transients after rapid flow interrruption can be assessed independent of complete
      pressure equilibration, and we have previously shown them to be correlated to
      resistive properties of the respiratory system. We wanted to determine whether
      these transients were an expression of acoustic properties of the air in the
      airways, or whether they were caused by an interaction of gas and lung tissue,
      and whether d was more sensitive than Rint to changes in airway mechanics.
      Bronchial challenge tests were carried out with cumulative doses of inhaled
      carbachol in 10 healthy children (aged 7-14 yrs) and 50 asthmatic children (aged
      5-15 yrs). The airflow interruptions were performed with a combined nebulizer
      shutter head, allowing resistance measurements with each breath. The frequency,
      and the damping factor of the postocclusional pressure transients changed
      significantly during carbachol challenge in both groups of children. The
      provocation dose (PD) at which the damping factor (d) of the oscillatory pressure
      transients increased more than 2 SD above the baseline mean ("variance-based",
      PDvb) was lower than the PDvb of the end-interruption resistance (Rint, EI).
      These changes in frequency and damping factor were reversible after inhaling
      salbutamol. These findings suggest that the damping properties of the
      postocclusional pressure transients after flow interruption can be used as a
      sensitive parameter to assess changes in airway mechanics during bronchial
      challenge test in children in whom pressure equilibration is frequently not
      achieved during airflow interruption due to airways obstruction.

PMID- 9032497
TI  - Short-term variations in oscillatory and spirometric lung function indices among
      school children.
AB  - The aim of this study was to compare immediate, daily and weekly variation in
      respiratory resistance measured by means of the forced oscillation technique
      (Rrs,FOT) to spirometric indices in 7-12 year old children with chronic
      respiratory symptoms. The lung function measurements were performed in 19
      children on 4 days, i.e. two consecutive days during two consecutive weeks. On
      each day, the measurements were carried out at the same time of day and always
      repeated three times. In addition, Rrs,FOT and spirometric lung function indices
      were compared with an exercise challenge test in 12 children. Intrasubject
      coefficients of variation (CoVs) for Rrs,FOT were larger than those for
      spirometric indices. Only in the immediately repeated measurements was the CoV of
      maximal expiratory flow at 25% vital capacity larger than that of Rrs,FOT (16.6
      vs 14.9%). At all time intervals, the smallest CoVs were observed in forced vital
      capacity (FVC) or in the ratio of forced expiratory volume in one second to FVC
      (2.0-2.6%). When excluding Rrs,FOT values which were not within 2 SD (0.11 kPa.L
      1.s) of the differences between the immediately repeated measurements, the CoV of
      the immediately repeated measurements of Rrs,FOT was reduced to 9.1%, being
      smaller than that of maximal mid-expiratory flow (10.1%). However, even then the
      day-to-day variation in Rrs,FOT was clearly larger (16.0%) than those of the
      airflow indices at specified lung volumes (7.2-8.3%). This was also true for the
      weekly variation. In the exercise challenge test, there were larger changes in
      Rrs,FOT values than in the spirometric indices, but Rrs,FOT was the most
      sensitive index to detect changes in the respiratory system. In conclusion, the
      variation in Rrs,FOT values was larger than that of most spirometric indices.
      When a reliability index was applied, the immediate variation in Rrs,FOT values
      was comparable to those of the airflow indices at specified lung volumes. Rrs,FOT
      was also the most sensitive index in the exercise challenge test, and therefore
      it seems to be suitable for detection of short-term functional changes in the
      respiratory system. However, the relatively low repeatability of Rrs,FOT over
      days and weeks may limit its applicability to longer-term follow-ups.

PMID- 9032498
TI  - Low diagnostic value of respiratory impedance measurements in children.
AB  - The aim of this study was to determine whether impedance values in children with
      various chronic respiratory complaints differed from those observed in symptom
      free children. Respiratory impedance was measured using the forced oscillation
      technique in 1,776 Dutch children aged 6-12 yrs. In addition to the commonly used
      parameters of resistance and reactance, further impedance parameters were
      obtained by using linear and quadratic regression to describe individual
      resistance and reactance curves as a function of frequency. Furthermore, the
      diagnostic value of the individual impedance parameters was evaluated by means of
      receiver operator characteristic (ROC) curves. Statistically significant
      differences in impedance values were found in girls with symptoms suggesting
      asthma compared to symptom-free girls, but not in boys. In children with chronic
      cough, impedance was not significantly different from the values of symptom-free
      children. The results obtained by the additional impedance parameters were
      comparable to those of the commonly used measures. We conclude that the
      diagnostic values of the impedance parameters appeared to be low, as no cut-off
      points were found to discriminate clearly between symptomatic and symptom-free
      children. These findings may reflect absence of functional abnormalities in
      symptomatic children at this age.

PMID- 9032499
TI  - Reference values for maximum work capacity in relation to body composition in
      healthy Dutch children.
AB  - Exercise performance is associated with physical development. For sick children,
      there is a need for parameters reflecting exercise performance, which should be
      easy to measure and should take their nutritional state into account. The aim of
      this study was to investigate the relationship between maximum work-load (Wmax)
      and body weight (BW) as well as fat-free mass (FFM) in healthy children
      performing an incremental maximum exercise test on a bicycle ergometer, and to
      develop reference values for Wmax corrected for nutritional state. A random
      sample of 158 children (77 boys and 81 girls), aged 12-18 yrs, underwent an
      incremental maximum exercise test on a bicycle ergometer. BW and FFM were also
      measured. Correlation analysis showed a significant association (p < 0.001)
      between BW and Wmax (boys: r = 0.82; girls: r = 0.73), and between FFM and Wmax
      (boys: r = 0.89; girls: r = 0.79). Two-way analysis of variance showed a
      significant effect of gender on variance of Wmax/BW ratio as well as Wmax/FFM
      ratio. The influence of age was significant for Wmax/FFM (p = 0.003), but not for
      Wmax/BW. The maximum workload/body weight ratio and the maximum workload/fat-free
      mass ratio are useful parameters of work capacity in bicycle exercise testing in
      children. The reference values (mean, SD, median, and percentiles) for boys and
      girls aged 12-18 years can be used to predict workload corrected for body
      composition in healthy and sick children.

PMID- 9032500
TI  - Pulmonary concentrations of dirithromycin and erythromycin during acute
      exacerbation of mild chronic obstructive pulmonary disease.
AB  - We compared the concentrations of dirithromycin and erythromycin at steady state
      in serum and the intrapulmonary region in patients suffering from acute
      exacerbation of mild chronic obstructive pulmonary disease. Twenty patients
      received dirithromycin, 500 mg given orally once daily for five consecutive days.
      The other 20 patients were treated with erythromycin base, which was administered
      orally four times daily at a total daily dose of 1000 mg for seven days. All
      patients were divided into eight groups, with five subjects in each group,
      according to sampling times (2, 4, 8, and hrs after the last dose) and treatment.
      After the erythromycin treatment mean serum concentrations were higher than those
      of dirithromycin treatment mean serum concentrations were higher than those of
      dirithromycin for upto 4 hours, but they were undetectable 24 hours after the
      last dose. At all time periods, the concentrations of dirithromycin in bronchial
      secretion, bronchial mucosa and epithelial lining fluid were greater than the
      concentration in serum. Concentrations of erythromycin were always lower than
      those of dirithromycin in the explored pulmonary sites. Our data demonstrated
      that a five day course of 500 mg of dirithromycin once daily induced higher
      concentrations and longer persistence in the various potential sites of pulmonary
      infection than a seven day course of 250 mg of erythromycin every 6 hrs. The
      shorter duration of therapy and the once daily dosing with good efficacy against
      common respiratory pathogens would be advantageous for patients and would be
      likely to promote better patient compliance and acceptability.

PMID- 9032501
TI  - The effects of a community-based pulmonary rehabilitation programme on exercise
      tolerance and quality of life: a randomized controlled trial.
AB  - The present multicentre study evaluates the differences in efficacy between a 3
      month rehabilitation programme including drug treatment, and a 3 month control
      period of drug treatment only, for asthmatic patients and patients with chronic
      obstructive pulmonary disease (COPD). The programme was run by physiotherapists
      in eight local practices, and included exercise training, patient education,
      breathing retraining, evacuation of mucus, relaxation techniques, and
      recreational activities. In a randomized controlled trial with a cross-over
      design, the effects of rehabilitation were evaluated 3 and 6 months after
      baseline measurements in terms of exercise tolerance and quality of life (QOL).
      Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min
      walking tests. QOL was evaluated by means of the Chronic Respiratory Disease
      Questionnaire (CRDQ). After 3 months, the patients who started with
      rehabilitation showed significant improvements in endurance time (421 s) and
      cardiac frequency (6 beats.min-1) during cycling, walking distance (39 m), and
      total CRDQ score (17 points) compared to the control group. These improvements
      were still significant after 6 months. Additional analysis indicated that the
      asthmatic patients and the patients with COPD responded to rehabilitation in a
      similar way, with the exception that there was a greater improvement in walking
      distance for asthmatics. Improvements in exercise tolerance were not
      significantly correlated with improvements in QOL. Rehabilitation of patients
      with asthma or chronic obstructive pulmonary disease in local physiotherapy
      practices improves exercise tolerance and quality of life.

PMID- 9032503
TI  - Long-term follow-up after surgical treatment of obstructive sleep apnoea by
      maxillomandibular advancement.
AB  - Obstructive sleep apnoea (OSA) is a common disorder with potentially serious
      consequences. If maxillary and mandibular deficiency, often in combination with a
      narrow posterior airway space is present, therapy of OSA by maxillomandibular
      osteotomy is possible. However, long-term follow-up of patients undergoing these
      procedures is lacking. We present the results of 15 OSA patients (1 female and 14
      males), who underwent maxillomandibular advancement surgery with a follow-up of
      at least 2 yrs. Polysomnography was performed before surgery, after 6-12 weeks,
      and 1 and 2 yrs postoperatively. Mean apnoea/hypopnoea index (AHI) decreased from
      51.4 events.h-1 before therapy to 5.0 events.h-1 6 weeks postoperatively, and was
      8.5 events.h-1 after 2 yrs. Oxygen saturation significantly increased following
      surgery. After 2 yrs, the AHI was < 10 events.h-1 in 12 out of 15 subjects. No
      significant changes were found comparing the 6-12 weeks versus the 2 year follow
      up data. The significant increase in stage 3/4 non-rapid eye movement (NREM)
      sleep and decrease in stage 1 NREM sleep, indicative of the restoration of normal
      physiological sleep structure, persisted in 14 of the 15 subjects 2 yrs
      postoperatively. Three patients, however, did not show satisfactory improvement 2
      yrs postoperatively; two showed obstructive and one central respiratory events.
      This study demonstrates that maxillomandibular advancement is successful in a
      high percentage of patients carefully selected by cephalometric and
      polysomnographic investigation. Postoperative success has proved to be stable
      over a period of 2 yrs. Further preoperative evaluation seems necessary in
      patients with predominantly mixed or central apnoeas.

PMID- 9032502
TI  - Comparison of two training programmes in chronic airway limitation patients:
      standardized versus individualized protocols.
AB  - This study tested the effect of two methods of training, one individualized at
      the heart rate corresponding to the gas exchange threshold (GET) and the other at
      the heart rate corresponding to 50% of maximal heart rate reserve, on maximal and
      submaximal cardiorespiratory response in 24 patients with chronic airway
      limitation (CAL). The patients were randomly assigned to either the
      individualized training group (IT; n = 12) or the standardized training group
      (ST; n = 12). The training programme consisted of 4 weeks of stationary bicycle
      exercise, 5 days.week-1. Before reconditioning began, the target level based on
      heart rate was not significantly different between groups (109 +/- 4 versus 110
      +/- 3 beats.min-1, in IT and ST, respectively). Post-training, a significant
      increase in symptom-limited oxygen uptake (V'O2.sl) and maximal O2 pulse was
      found in IT, whereas ST exhibited no significant change. In each group, GET was
      statistically increased in much the same way as V'O2,sl, with a higher increase
      in IT (p < 0.01) than ST (p < 0.05). Nevertheless, IT exhibited a concomitant and
      gradual decrease in minute ventilation (V'E), carbon dioxide production (V'CO2),
      and venous lactate concentration ([La]), whereas ST presented no significant
      change in these parameters (intergroup p < 0.01). Breathing pattern was also
      altered after IT, at the same metabolic level and at the same ventilation level
      (intergroup p < 0.05). Cardiac responses were modified in the two groups. At the
      same metabolic level, a significantly lower cardiac frequency was found both for
      IT and ST (intragroup p < 0.05 after training). In contrast, the increase in O2
      pulse was only significantly higher in It after training. These data show the
      greater efficiency of an individualized training protocol based on determination
      of gas exchange threshold as compared to a standardized protocol, in improving
      exercise performance, when applied to a patient group. Despite an apparently
      similar target training level, the individualized method clearly optimized the
      physiological training effects in patients with chronic airway limitation and,
      more particularly, decreased their ventilatory requirement.

PMID- 9032504
TI  - Influence of uvulopalatopharyngoplasty on alpha-EEG arousals in nonapnoeic
      snorers.
AB  - Arousals are more numerous in heavy snorers than in nonsnorers and might be a
      cause of excessive daytime sleepiness (EDS) in these patients. The present study
      investigated whether treatment of snoring by uvulopalatopharyngoplasty (UPPP) had
      an influence on sleep microstructure in nonapnoeic snorers. The polysomnographic
      records of 10 nonapnoeic snorers were reviewed retrospectively and arousals
      scored according to the American Sleep Disorders Association (ASDA) 3 s
      definition. Scores for snoring, EDS and polysomnographic data were compared
      before and after UPPP (mean (+/-SD) time interval 249 +/- 183 days). UPPP
      resulted in a subjective improvement of snoring and a significant decrease in the
      arousal index (mean 14.6, 95% confidence interval (95% CI) 8.5-20.8 vs mean 9.1,
      95% CI 6.6-11.5) (p = 0.01). EDS and the amount of slow-wave sleep remained
      unchanged. Uvulopalatopharyngoplasty resulted in an improvement of subjective
      snoring and a significant decrease of arousals in nonapnoeic snorers. Although
      these data do not provide any insight into whether the improvement observed can
      be maintained on a long-term basis, uvulopalatopharyngoplasty can be considered
      as a useful treatment modality to reduce sleep fragmentation and snoring in
      nonapnoeic snorers.

PMID- 9032505
TI  - Lack of evidence for diaphragmatic fatigue over the course of the night in
      obstructive sleep apnoea.
AB  - The aim of this study was to determine whether diaphragmatic fatigue develops
      over the course of the night in patients with obstructive sleep apnoea (OSA).
      Patients with severe OSA underwent overnight polysomnography with the addition of
      gastric and oesophageal catheters for measurement of transdiaphragmatic pressure
      (Pdi) (n = 7) and a gastro-oesophageal electrode for determination of
      diaphragmatic electromyogram (EMGdi) (n = 5). Analyses of Pdi and EMGdi were
      performed to detect fatigue during the large inspiratory efforts at the end of
      apnoeas in Stage 2 sleep at the beginning and end of the night. Measurements
      included Pdi values, shape analysis of the Pdi waveform, the relaxation rate (tau
      R) of Pdi, EMGdi and its relationship to Pdi, and the centroid frequency (fc) of
      EMGdi. End of apnoeic Pdi and EMGdi increased from the beginning to end of the
      night (e.g. 19 +/- 14% increase in Pdi; p < 0.05). The rate of increase in Pdi
      and EMGdi during apnoeas did not change. The Pdi versus EMGdi relationship was
      linear, and remained unchanged over the course of the night. There was no
      significant change in the shape of the Pdi waveform, and there were no changes in
      tau R from the beginning to the end of the night (0.13 +/- 0.01 s for both
      periods). There was also no shift in the fc of the EMGdi power spectrum (94 +/- 5
      vs 93 +/- 6 Hz; NS), and no change in the relationship of fc to Pdi or EMGdi from
      the beginning to the end of the night. These findings do not support the
      development of diaphragmatic fatigue over the course of the night in obstructive
      sleep apnoea.

PMID- 9032506
TI  - Respiratory dysfunction in multiple sclerosis: a prospective analysis of 60
      patients.
AB  - This study aimed to determine the relationship between pulmonary function,
      respiratory muscle function and neurological function in multiple sclerosis (MS).
      Sixty patients (27 males and 33 females) aged 27-75 yrs (mean +/- SD 48 +/- 12
      yrs) were prospectively studied. The Kurtzke Expanded Disability Status Scale
      (EDSS; range 0-10) score was 6.5 +/- 1.5; and the different Functional Systems
      Scores (FSS; ranges 0-5 and 0-6) were: pyramidal 3.4 +/- 1.1; brain stem 1.9 +/-
      1.2; mental 1.3 +/- 0.9; cerebellar 2.2 +/- 1.0; sphincter 1.8 +/- 1.5; visual
      1.4 +/- 1.4; and sensory 2.0 +/- 1.5. Results of lung function tests were: vital
      capacity (VC) 80 +/- 23% of predicted; single-breath transfer factor of the lung
      for carbon monoxide (TL, CO, sb) 83 +/- 17% pred; maximal static expiratory mouth
      pressure (MEP) 30 +/- 16% pred; and maximal static inspiratory mouth pressure
      (MIP) 47 +/- 23% pred, indicating a marked respiratory muscle dysfunction, with a
      minor restrictive defect. In 70% of the patients, a transcutaneous oxygen
      saturation (Stc, O2) of less than 92% at night was found. Comparison of lung
      function and disability scores showed that the abnormalities in both tended to be
      correlated to each other, and that this was significant for EDSS versus lung
      volumes, for most FSS with VC, and also for some FSS with MEP and/or MIP.
      Duration of disease was significantly correlated with the EDSS, but not with the
      different FSS scores (with the exception of mental status) and not with lung
      function. Multiple sclerosis leads to lung function abnormalities attributable to
      respiratory pump dysfunction.

PMID- 9032507
TI  - Lung function and clinical outcome in postpolio patients: a prospective cohort
      study during 11 years.
AB  - The object of this investigation was to prospectively study the annual decline in
      lung function in a cohort of postpolio patients, and to determine the usefulness
      of initial lung function tests in the prediction of a subsequent poor outcome.
      Cross-sectional data were analysed in 55 patients from the total cohort of 350
      survivors of poliomyelitis in our admission area of 550,000 inhabitants.
      Longitudinal data (> 5 yrs, average 8.9 yrs) were available for 31 patients.
      Seventeen of the patients had a poor outcome (13 were started on domiciliary
      artificial ventilation and five died from respiratory failure; with one overlap).
      At the time of entry to the study (on average 4.3 years before the poor outcome),
      these patients had a lower vital capacity (VC) (43 vs 65% of predicted; p < 0.01)
      and arterial oxygen tension (Pa,O2) (9.9 vs 11 kPa; p < 0.05) and a higher
      arterial carbon dioxide tension (Pa,CO2) (6.0 vs 5.0 kPa; p < 0.01). They also
      had a more rapid increase in Pa,CO2 (0.3 vs 0.03 kPa.yr-1; p < 0.01), but the
      difference in decline in VC (40 vs 30 mL.yr-1) was not significant. Initial VC <
      50% of predicted and/or Pa,CO2 > 6 kPa was associated with a poor prognosis. In
      conclusion, annual decline in vital capacity was not abnormally rapid but annual
      increase in arterial carbon dioxide tension was higher in patients with a poor
      outcome. Initial determination of vital capacity and initial and repeated blood
      gas analysis appear to be useful in identifying high-risk postpolio patients.

PMID- 9032508
TI  - Respiratory resistive impedance in obstructive patients: linear regression
      analysis vs viscoelastic modelling.
AB  - The aim of this study was to test the ability of a simple two segment model to
      describe the frequency dependence of resistive impedance in obstructive patients,
      and to investigate the significance of parameters derived from this model. The
      study was performed in 38 patients, in the basal state and after inhalation of
      200 micrograms salbutamol. Impedance data measured over 4-32 Hz were fitted by a
      general four parameter viscoelastic model describing gas redistribution, and
      completed by an inertial component. This model yielded Newtonian resistance
      (Rmin) and maximal resistance (Rmax = Rmin plus delayed resistance due to gas
      redistribution). Resistive impedance data were also submitted to linear
      regression analysis over the 4-16 and 17-32 Hz frequency ranges, which
      respectively, yielded resistive impedance extrapolated at 0 Hz (R0) and resistive
      impedance estimated at 32 Hz (R32). R0 and R32 were compared to Rmax and Rmin,
      respectively. The airway response to salbutamol inhalation was assessed by the
      percentage changes in these parameters (R0%, R32%, Rmax%, and Rmin%,
      respectively). Significant linear correlations (p < 0.0001) were found between R0
      and Rmax, R32 and Rmin, and R0% and Rmax%. Furthermore, the linear regression
      lines of R0 vs Rmax, and R0% vs Rmax%, were not significantly different from the
      identity line. These results demonstrate that resistive impedance extrapolated at
      zero frequency is equivalent to maximal resistive impedance, and can be proposed
      as an index, not only of the level of airway obstruction, but also of its
      reversibility.

PMID- 9032509
TI  - The effect of dipyridamole and theophylline on hypercapnic ventilatory responses:
      the role of adenosine.
AB  - The purine nucleoside, adenosine, has been implicated as a neuromodulator in
      central respiratory depression during prolonged exposure to hypoxia. It may also
      be a mediator of hypoxic hyperpnoea, acting on the carotid bodies. As there may
      be adenosine-sensitive mechanisms of hypoxic respiratory control, we sought to
      determine whether adenosine might be involved as a respiratory modulator in
      another central but non-oxygen-related control mechanism, the ventilatory
      response to hyperoxic hypercapnia. Twelve normal subjects were studied following
      3 days of oral treatment with placebo, dipyridamole (which potentiates adenosine
      effects by inhibiting cellular uptake), and theophylline (a specific adenosine
      antagonist of cell surface receptors). The drugs were given in a random order,
      double-blind fashion. Resting end-tidal carbon dioxide tension (PET,CO2) and the
      maximum rate of isometric inspiratory pressure change at the mouth ((dP/dt) max),
      an index of respiratory drive, were determined in all subjects on each treatment.
      Hyperoxic, hypercapnic ventilatory responses were determined in seven of these
      subjects using a rebreathing technique. For each hypercapnic response, minute
      ventilation (V1E) and (dP/dt) max were plotted against PET,CO2 breath-by-breath.
      Resting PET,CO2 breathing room air was lower with theophylline (5.47 (SD 0.21)
      kPa) than with placebo (5.74 (0.26) kPa) or dipyridamole (5.86 (0.34) kPa), with
      no significant drug differences in resting (dP/dt)max. However, neither the slope
      nor the PET, CO2 intercept of the relationship between ventilation or respiratory
      drive and PET, CO2 were altered by the study drugs under hyperoxic conditions. We
      conclude that endogenous adenosine-related mechanisms are unlikely to be involved
      in determining either the sensitivity or the threshold of the ventilatory
      response to carbon dioxide under hyperoxic conditions. However, in normoxia, a
      centrally-acting, tonic, adenosine-mediated, respiratory modulation is not ruled
      out.

PMID- 9032510
TI  - Influence of awareness of the recording of breathing on respiratory pattern in
      healthy humans.
AB  - This study was designed to test whether awareness of the measurement of breathing
      influences the breathing pattern in healthy subjects under routine laboratory
      conditions. Seventy four subjects (40 females and 34 males), aged 21-63 yrs, were
      studied under three different conditions whilst their breathing was being
      recorded for 5 min by means of inductance plethysmography (Respitrace): 1)
      subjects were misled into believing that their breathing was not being recorded
      but that they had to wait for 5 min whilst equipment was calibrated; 2) subjects
      were instructed that their breathing pattern was being recorded for 5 min; 3) the
      subject's breathing was recorded for 5 min with mouthpiece and pneumotachograph.
      The first two conditions were randomized. The Respitrace was calibrated by means
      of multiple linear regression carried out during the 5 min period of quiet
      breathing through a mouthpiece. Awareness of the recording of breathing caused
      prolongation of inspiratory (tI) and expiratory time (tE). Breathing through the
      mouthpiece resulted in an increase of tI, tE and tidal volume (VT). The breathing
      irregularities (sighs and end-expiratory pauses) decreased when subjects were
      aware of the recording of breathing and nearly disappeared when subjects breathed
      through the mouthpiece. The end-tidal carbon dioxide concentration was not
      significantly different between the three conditions. Mouthpiece breathing often
      induced some respiratory discomfort and even anxiety, particularly in females.
      Awareness by the subject that his or her breathing was being recorded altered the
      spontaneous breathing pattern, mainly the breathing frequency. In addition, use
      of a mouthpiece markedly increased tidal volume, particularly in females in whom
      mouthpiece breathing induced more complaints than in males.

PMID- 9032511
TI  - Unsteadiness of breathing in patients with hyperventilation syndrome and anxiety
      disorders.
AB  - The breathing pattern of 399 patients with hyperventilation syndrome (HVS) and/or
      with anxiety disorders and that of 347 normal controls was investigated during a
      5 min period of quiet breathing and after a 3 min period of voluntary
      hyperventilation. The diagnosis of HVS was based on the presence of several
      suggestive complaints occurring in the context of stress, and reproduced by
      voluntary hyperventilation. Organic diseases as a cause of the symptoms were
      excluded. The anxiety disorders were diagnosed by means of an abbreviated version
      of the Anxiety Disorders Interview Schedule (ADIS). There was a large overlap
      between the two diagnoses. Simply breathing via a mouthpiece and pneumotachograph
      made end-tidal CO2 fractional concentration (FET,CO2) decrease progressively both
      in hyperventilators and in patients with anxiety disorders, but not in normals.
      At the start of the measurement the FET,CO2 was not different between patients
      and healthy subjects. In patients < or = 28 yrs, the decrease of FET,CO2 resulted
      from a higher tidal volume, and in patients > or = 29 years from an increase in
      frequency. After voluntary hyperventilation, the recovery of FET,CO2, was delayed
      in patients, due to a slower normalization of respiratory frequency in females
      and in older males, and of tidal volume in younger males, and also due to less
      frequent end-expiratory pauses. When breathing was recorded first by means of
      inductive plethysmography (Respitrace), the progressive decline of FET,CO2 seen
      in patients was not observed: from the onset of the recording, FET,CO2 was
      reduced in patients. It did not change further when, immediately afterwards, the
      subject switched to mouthpiece breathing. The finding that breathing through a
      mouthpiece induces hyperventilation in patients and that recovery of FET,CO2 is
      delayed after voluntary hyperventilation, suggests that the respiratory control
      system is less resistant to challenges (mouthpiece or voluntary hyperventilation)
      in those patients. On the other hand, the lower values of FET,CO2 measured during
      recording by means of a Respitrace probably result from a challenge, prior to the
      recordings, induced by the fitting of the measuring device to the patient. This
      unsteadiness of breathing characterizes patients with hyperventilation syndrome
      and those with anxiety disorders, but is not sufficiently sensitive to be used
      for individual diagnosis.

PMID- 9032512
TI  - Patient-ventilator interaction and inspiratory effort during pressure support
      ventilation in patients with different pathologies.
AB  - The aim of this study was to evaluate whether pressure support ventilation (PSV)
      requires different diaphragmatic efforts and patient-ventilator matching,
      according to the underlying disease. Four groups of patients requiring PSV were
      studied: Group A, recovering from an episode of acute respiratory failure due to
      adult respiratory distress syndrome (ARDS); Group B, with postsurgical
      complications; and two subsets of chronic obstructive pulmonary disease (COPD)
      patients, with "normal" static compliance of the respiratory system (Cst,rs)
      (Group C) or elevated Cst,rs (Group D). Ventilatory pattern, transdiaphragmatic
      pressure (Pdi), the pressure-time product of the diaphragm (PTPdi), static
      (PEEPi,stat) and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn),
      Cst,rs and resistance of the total respiratory system (Rrs) were recorded. The
      matching between patient and ventilator was analysed, recording the number of
      "ineffective efforts" (inspiratory efforts not efficient enough to trigger a new
      ventilator cycle, despite a positive deflection in Pdi). A satisfactory blood gas
      equilibrium arterial oxygen saturation (Sa,O2 > 93%, with a pH > 7.32) was
      obtained in the various groups with different levels of PSV. Minute ventilation
      was found to be significantly higher in Groups A and B, due to the longer
      expiratory time (tE) in the COPD groups. Group A (2 out of 7), Group B (3 out of
      7), Group C (3 out of 5) patients showed sporadic "ineffective efforts". All
      Group D patients manifested continuous mismatching with the ventilator, so that
      the pressure-time product of the diaphragm per minute (PTPdi/min), reflecting the
      metabolic work of the diaphragm, was not different in the four groups. Tidal
      volume and the spontaneous inspiratory efforts were similar in the four groups,
      but the number of breaths delivered by the ventilator was significantly higher in
      Groups A and B. The application of different levels of pressure support
      ventilation in patients with acute respiratory failure due to different
      pathologies, led them to breathe with comparable pressure time product of the
      diaphragm. The majority of the patients showed mismatching with the ventilator,
      although this effect was more pronounced in the groups with chronic obstructive
      pulmonary disease.

PMID- 9032513
TI  - Comparison of two different modes for noninvasive mechanical ventilation in
      chronic respiratory failure: volume versus pressure controlled device.
AB  - The most commonly used mode of noninvasive mechanical ventilation (NMV) is volume
      controlled intermittent positive pressure ventilation (IPPV). Pressure support
      ventilation has recently become increasingly popular, but its merits have not
      been clearly defined. In an open, nonrandomized follow-up study, we evaluated two
      modes of NMV, volume-controlled (IPPV) and pressure-controlled ventilation (PCV)
      over 6 months in 30 consecutive patients (24 males and 6 females, aged 49 +/- 19
      yrs) with chronic respiratory failure (CRF). The baseline assessments comprised
      both physiological and subjective data. In all cases, nasal IPPV was initially
      administered for 1 month, followed by a second month of nasal PCV. Thereafter,
      responders or nonresponders to PCV were defined according to the patients'
      subjective symptom score and/or the recurrence of hypercapnia. During the IPPV
      phase, in all but two patients the subjective and objective parameters improved
      significantly. During the following 1 month PCV phase, stabilization was
      maintained in 18 patients ("responders"), while 10 patients were defined as
      "nonresponders". In nonresponders, hypercapnia increased (arterial carbon dioxide
      tension (Pa,CO2): 5.7 +/- 0.4 to 6.6 +/- 0.5 kPa; p < 0.05) and symptom scores
      decreased. Compared with responders, nonresponders had a lower mean nocturnal
      arterial oxygen saturation (Sa,O2) (p < 0.05) and a higher daytime Pa,CO2 (p <
      0.05) at baseline. We con clude that the majority of patients suffering from
      chronic respiratory failure who are initially satisfactorily ventilated with
      intermittent positive pressure ventilation may also be adequately maintained with
      pressure-controlled ventilation. However, there is a subgroup with more severe
      chronic respiratory failure at baseline, in whom pressure-controlled ventilation
      is inadequate. After 4 weeks of treatment with pressure-controlled ventilation,
      the subjective scores and the arterial carbon dioxide tension values reliably
      distinguished between long-term responders and nonresponders to pressure
      controlled ventilation.

PMID- 9032514
TI  - Additive nature of distension and surfactant perturbation on alveolocapillary
      permeability.
AB  - The aim of this study was to determine whether the effects of alveolar distention
      and surfactant dysfunction on alveolocapillary barrier function are different and
      additive. Pulmonary clearance of aerosolized technetium-99m-labelled human serum
      albumin (99mTc-HSA) was used to characterize barrier function after perturbing
      the surfactant system with the detergent dioctyl sodium sulphosuccinate either
      singly or in combination with large tidal volume ventilation (LTVV). Clearance
      was measured for 3 h (Experimental ventilation) in four groups (n = 6 each) of
      rabbits: 1) Controls; 2) Detergent; 3) LTVV; and 4) Detergent + LTVV. Restoration
      of clearance (Recovery) was studied for 3 h under conventional ventilation. The
      half-life of clearance (t 1/2) decreased during LTVV (305 min) compared to 1,055
      min in Controls. Detergent induced a biexponential clearance with slow (t 1/2S)
      and fast (t 1/2F) half-lives of 670 and 15.4 min, respectively. The fast fraction
      (fF) was 0.20. Clearance in the Detergent + LTVV group was also biexponential.
      The t 1/2F and fF were similar to the Detergent group. The t 1/2S was similar to
      the LTVV group. The fF in this group increased to 0.36 during Recovery (p < 0.01
      versus Detergent group and p < 0.05 versus Experimental ventilation). The diverse
      kinetics of clearance during large tidal volume ventilation and surfactant
      dysfunction suggest the presence of different mechanisms affecting the barrier.
      The mechanisms have additive characteristics, which superimpose to produce lung
      injury.

PMID- 9032515
TI  - The effect of nitrous oxide on the measurement of single-breath transfer factor.
AB  - One hour after a bone marrow biopsy and inhalation of Entonox gas (50% nitrous
      oxide (N2O) and 50% oxygen), a patient had a markedly reduced transfer factor of
      the lung for carbon monoxide (TL,CO). Three hours after Entonox, the patient had
      a normal TL,CO. Since carbon monoxide (CO) and N2O have similar spectral
      wavelengths, it was proposed that residual N2O in the lungs was interfering with
      the infra-red analysers used to detect CO concentrations. Experiments were
      performed to verify the "interference" effect and its duration. Five healthy
      volunteers performed serial triplicate TL,CO measurements over 3 h on two
      randomized days (Control vs N2O). The first triplicate TL,CO on each day served
      as a baseline measurement. Following the baseline measurement on the N2O day,
      each subject inhaled Entonox for 10 min. To serve as a control for the infrared
      effect, the identical protocol was repeated using a gas chromatography method for
      TL,CO determination. The infra-red method showed a marked reduction (> 50%) in
      TL,CO 30 min after N2O inhalation. This reduction did not return to baseline
      levels for at least 2 h. In comparison, the gas chromatography method showed no
      significant reduction in TL,CO. In a group of healthy nonsmoking subjects, N2O
      markedly affected the measurement of the transfer factor of the lungs for carbon
      monoxide using infra-red analysers. The time course over which the measurement
      was reduced was at least 2 h for a 10 min inhalation period. The effect was
      entirely due to a measurement error associated with infra-red technology.

PMID- 9032516
TI  - The acoustic properties of capsaicin-induced cough in healthy subjects.
AB  - Acoustic analysis of cough both in the time and frequency domain has been
      reported using voluntary and spontaneous cough. The main aim of this study was to
      discover whether such analysis of capsaicin-induced cough enables differences
      between normal subjects to be recognized. We present data from 13 healthy
      subjects (with normal lung function and no history of respiratory disease) using
      a new method of acoustic analysis, which presents the data in three graphical
      forms: 1) spectrogram; 2) overall spectral energy, 3) root mean square (RMS)
      pressure plots. Using the RMS sound pressure traces, different subjects had
      either two peaks, a single peak or multiple peaks. The occurrence of single and
      multiple peaks has previously been associated with disease states but we found
      them in normal subjects. The number of peaks and the visual pattern of the
      spectrogram was reproducible within and specific to each individual over time.
      During a peal of coughs in a single expiration, the peak amplitude of successive
      coughs decreased as lung volume reduced. Despite similarities in the overall
      spectral energy between individuals, there were marked differences in the small
      visual details of the spectrograms. However, in an individual, these small
      details were remarkably constant both within and between days, and can be
      regarded as a "cough signature". This type of spectrographic analysis provides a
      new approach to the analysis both of normal and abnormal cough sounds, and has
      identified similarities and differences in capsaicin-induced cough in normal
      individuals. It has potential as a tool with which to study the pathophysiology
      of cough.

PMID- 9032517
TI  - Lung volume reduction surgery for emphysema.
AB  - Lung volume reduction surgery (LVRS) is performed to alleviate dyspnoea of
      selected patients with severe pulmonary emphysema and to improve their pulmonary
      function, performance in daily activity and quality of life. By resection of
      destroyed lung areas the achievable improvements in function may consist of: 1) a
      reduction in hyperinflation resulting in amelioration of diaphragm and chest wall
      mechanics; 2) an increase of elastic recoil pressure, thereby augmenting
      expiratory flow rates; and 3) possibly an improvement in gas exchange. Meticulous
      selection of suitable patients, refinements in operative techniques,
      anaesthesiological and postoperative management has lowered perioperative
      mortality to less than 5% in groups who are experienced with this type of
      procedure. The best functional results are achieved by bilateral resection, which
      can either be performed by median sternotomy or by video-assisted thoracoscopy
      (VAT). The average increase in forced expiratory volume in one second (FEV1),
      obtained by bilateral resection in patients already receiving optimal medical
      therapy ranges 32-93%, and the reduction in hyperinflation, assessed by a
      decrease in total lung capacity ranges 15-20%. These favourable improvements have
      been reported to last in most of the patients for at least one year.

PMID- 9032518
TI  - Physiology and pathophysiology of pleural fluid turnover.
AB  - The pleural space contains a tiny amount (approximately 0.3 mL.kg-1) of
      hypooncotic fluid (approximately 1 g.dL-1 protein). Pleural fluid turnover is
      estimated to be approximately 0.15 mL.kg-1.h-1. Pleural fluid is produced at
      parietal pleural level, mainly in the less dependent regions of the cavity.
      Reabsorption is accomplished by parietal pleural lymphatics in the most dependent
      part of the cavity, on the diaphragmatic surface and in the mediastinal regions.
      The flow rate in pleural lymphatics can increase in response to an increase in
      pleural fluid filtration, acting as a negative feedback mechanism to control
      pleural liquid volume. Such control is very efficient, as a 10 fold increase in
      filtration rate would only result in a 15% increase in pleural liquid volume.
      When filtration exceeds maximum pleural lymphatic flow, pleural effusion occurs:
      as an estimate, in man, maximum pleural lymph flow could attain 30 mL.h-1,
      equivalent to approximately 700 mL.day-1 (approximately 40% of overall lymph
      flow). Under physiological conditions, the lung interstitium and the pleural
      space behave as functionally independent compartments, due to the low water and
      solute permeability of the visceral pleura. Pleural fluid circulates in the
      pleural cavity and intrapleural fluid dynamics may be represented by a porous
      flow model. Lubrication between lung and chest wall is assured by oligolamellar
      surfactant molecules stratified on mesothelial cells of the opposing pleurae.
      These molecules carry a charge of similar sign and, therefore, repulse each
      other, assuring a graphite-like lubrication.

PMID- 9032519
TI  - Heart-lung interactions: applications in the critically ill.
AB  - Since the circulatory and pulmonary systems are both driven by pressure and share
      space in the thorax, it is inevitable that they interact. These mechanical
      interactions, whilst relatively few in number, are protean in their
      manifestations. The circulatory system of the critically ill is often
      particularly susceptible to interference from respiration. Compensatory reserve
      is limited, ventilatory effort increased, and many critical care respiratory
      interventions place strain on the circulation, not seen in health. This review
      will examine the basic physiological mechanisms through which the pulmonary and
      circulatory systems interact. These mechanisms will then be applied to a variety
      of weaning, positive end-expiratory pressure (PEEP), and cardiopulmonary
      resuscitation techniques. It is hoped that this will provide the tools to
      understand clinical observations which would otherwise appear inexplicable.

PMID- 9032520
TI  - Occupational asthma due to a widely used soft solder flux not containing
      colophony.
AB  - A 19 year old woman presented with symptoms suggestive of occupational asthma.
      The causative agent was thought to be a soft solder flux, which did not contain
      colophony. The diagnosis was established by specific inhalation challenge tests,
      which demonstrated both late asthmatic reactions and short-lived increases in
      airway responsiveness.

PMID- 9032521
TI  - Reactive airways dysfunction syndrome due to chlorine: sequential bronchial
      biopsies and functional assessment.
AB  - Very little information is available on the acute histopathological bronchial
      alterations caused by reactive airways dysfunction syndrome (RADS). We had the
      opportunity to carry out sequential bronchial biopsies in a subject with RADS due
      to chlorine (60 h, 15 days, 2 and 5 months after the acute exposure), and also to
      assess spirometry and bronchial responsiveness to methacholine. A 36 year old
      worker in a water-filtration plant (nonsmoker) abruptly inhaled high
      concentrations of chlorine on September 12, 1994. He experienced immediate nasal
      and throat burning, retrosternal burning and wheezing, and these symptoms
      persisted during and after the workshift. Two days later, he complained of
      retrosternal burning, dyspnoea and wheezing. Inspiratory wheezing was documented.
      His forced expiratory volume in one second (FEV1) was 66% of predicted and the
      provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was
      slightly abnormal (2.5 mg.mL-1). On the following day, the patient underwent
      bronchial biopsies, which showed almost complete replacement of the epithelium by
      a fibrinohaemorhagic exsudate. The subject was prescribed inhaled steroids.
      Fifteen days after the accident, the PC20 was improved to 6 mg.mL-1. Bronchial
      biopsies showed considerable epithelial desquamation with an inflammatory exudate
      and swelling of the subepithelial space. Five weeks after the accident, the PC20
      was normal (57 mg.mL-1). Inhaled steroids were stopped. Two months after the
      accident, the PC20 deteriorated to 4 mg.mL-1. Biopsies then showed regeneration
      of the epithelium by basal cells and there was still a pronounced inflammatory
      infiltrate. Inhaled steroids were restarted. Three and five months later, the
      PC20 was normal (24 mg.mL-1). Bronchial biopsies showed a greatly improved
      epithelium and reduction of the inflammatory infiltrate. This case report shows
      that reactive airways dysfunction syndrome can cause acute, marked, though
      partially reversible, histological abnormalities. Inhaled steroids may modulate
      changes in bronchial responsiveness in this condition.

PMID- 9032522
TI  - Necrotizing sarcoid granulomatosis with extrapulmonary involvement.
AB  - Pulmonary lesions, with sarcoid-like granulomas exhibiting noncaseous necrosis,
      with associated granulomatous arteritis fulfil the diagnostic criteria of
      necrotizing sarcoid granulomatosis (NSG). We report the case of a woman who
      presented with recurrent headaches, transient right hemipareses and left-sided
      ophthalmoplegia. An excised left retro-orbital lesion demonstrated sarcoid like
      changes, and the illness responded to steroid therapy. Twelve years later, the
      patient developed a tumour in the right lung. The resected specimen showed the
      histological hallmarks of NSG, and careful review of the retro-orbital lesion,
      removed 12 years previously, revealed similar histology. Extrapulmonary
      involvement in NSG is rare and has been histologically proven on only one
      previous occasion. The presentation of necrotizing sarcoid granulomatosis in two
      different systems 12 years apart is unusual and was considered worth reporting.

PMID- 9032523
TI  - Chronic pneumonia caused by Rhodococcus equi in a patient without impaired
      immunity.
AB  - A 48 year old, human immunodeficiency virus (HIV)-negative, immunocompetent male
      patient had a chronic progressive pulmonary infiltrate, without radiological
      cavitation, in the middle lobe of the right lung produced by Rhodococcus equi. He
      reported direct contact with a diseased dog. The patient was diagnosed by
      thoracotomy and treated by lobectomy. After 16 months of follow-up, the patient
      was asymptomatic and had neither recurrence nor immunological disturbances.

PMID- 9032524
TI  - Priming of circulating human eosinophils following late response to allergen
      challenge.

PMID- 9032525
TI  - Pulmonary diffusion impairment following heart transplantation: a prospective
      study.

PMID- 9032526
TI  - Human androgen receptor expression in prostate cancer following androgen
      ablation.
AB  - OBJECTIVE: Metastatic prostate cancer kills patients because their tumor cells
      fail to respond to combined androgen blockade (CAB) or respond and then relapse.
      To understand the molecular basis of androgen-insensitive growth of prostate
      tumor cells, we evaluated changes in human androgen receptor gene (hAR) mRNA
      levels in patients with prostate cancer treated with CAB. METHODS: The study was
      carried out using quantitative reverse-transcriptase polymerase chain reaction
      analysis. The level of hAR mRNA were compared to serum prostate-specific antigen
      and the mutant status of p53 in the tumor. RESULTS: hAR was expressed in 44 of 46
      tumors from untreated patients, as opposed to 30 of 45 from those who had
      received CAB (p = 0.001). These 30 were from 8 of 9 stage D patients and from 22
      of 36 patients on downsizing CAB therapy prior to radical prostatectomy.
      Expression was most often seen in high stages (56% of stage B vs. 89% of stage D)
      and high grades (52% of Gleason 3-7 vs. 92% of Gleason 8-10, p = 0.015). No tumor
      with a missense p53 mutation had hAR expression following CAB. Twenty-two
      patients following CAB were found to have undetectable serum prostate-specific
      antigen levels, while their tumor expressed hAR. CONCLUSIONS: hAR expression
      after CAB is seen preferentially in high-grade, high-stage tumors, the type of
      prostate carcinomas that fail to have a durable remission. Undetectable serum
      prostate-specific antigen from tumors that remain hAR positive may predict
      relapse after hormonal ablative therapy.

PMID- 9032527
TI  - The importance of continued endocrine treatment during chemotherapy of hormone
      refractory prostate cancer.
AB  - OBJECTIVE: It is unclear if continuing with androgen deprivation in hormone
      refractory prostate cancer is of any benefit. We report here 3 cases where
      continuation of androgen deprivation was essential in maintaining the response to
      chemotherapy. RESULTS: In the 3 patients there was an initial response to
      chemotherapy before relapse, as assessed by prostate-specific antigen levels.
      However, restarting the previously ineffective hormone therapy resulted in
      continued response to chemotherapy. CONCLUSIONS: In some patients continued
      androgen deprivation is essential to the response to chemotherapy. Presumably, in
      hormone-relapsed disease a significant proportion of the tumour can still be
      responsive to androgen deprivation.

PMID- 9032528
TI  - Impact of minimal lymph node metastasis on long-term prognosis after radical
      prostatectomy.
AB  - OBJECTIVES: In the management of clinically localized prostate cancer,
      understanding is of major concern. There is a considerable therapeutic dilemma in
      those patients in whom staging lymphadenectomy prior to intended radical
      prostatectomy reveals lymph node metastases. METHODS: Pelvic lymph node
      dissection and radical retropubic prostatectomy were performed in 132 consecutive
      patients. Patients with extracapsular disease and/or positive lymph nodes
      received adjuvant radiotherapy. Median follow-up after surgery was 7 years and 2
      months. To study the influence of minimal lymph node metastasis, category pN1 was
      further subdivided into pN1.1 and pN1.2. Involvement of the prostatic capsule was
      either classified as infiltration (pT3.1) or performation (pT3.2) of the capsule.
      RESULTS: Disease-free survival after 10 years was 58% in patients with negative
      nodes, 37% in category pN1.1, 25% in category pN1.2 and 10% in category pN2.
      Corrected overall survival was 83% for node-negative patients and 73% for
      category pN1.1, but it was only 33% for pN1.2 and 29% for pN2. Patients in
      category pT3.1 had a statistically significant better survival than those in
      pT3.2. CONCLUSIONS: We conclude that radical prostatectomy combined with adjuvant
      radiotherapy is a valuable option in prostate cancer patients with minimal lymph
      node metastasis. When compared to infiltration of the capsule, complete capsular
      perforation does adversely affect prognosis.

PMID- 9032529
TI  - New aspects of urolithiasis in France. GERBAP: Groupe d'Evaluation et de
      Recherche des Biologistes de l'Assistance Publique des Hopitaux de Paris.
AB  - OBJECTIVE: To confirm epidemiological studies showing a continuous progression of
      calcium oxalate nephrolithiasis in western countries, we investigated some
      aspects of the evolution of stone disease in France. METHODS: Calculi collected
      from 1977 to 1993 in 10,438 adult French patients were analyzed by infrared
      spectroscopy. Only 8,631 well-documented cases were available. The anatomical
      location, the removal mode of calculi, and the time evolution of stone
      composition were studied. RESULTS: The stones were more often retained in the
      upper urinary tract in females than in males and needed urological removal. Uric
      acid stones were more frequently observed on the left side in both sexes (p <
      0.0001). Extracorporeal shock wave lithotripsy seems to have been used for a time
      in calculi which would have been spontaneously discharged. Calcium oxalate stones
      were preponderant, but their proportion did not change in both sexes. A
      significant decrease of the proportion of calcium phosphate stones was observed
      in females (p < 0.0001), probably responsible for the increase of the male/female
      sex ratio from 1.7 to 2.4. CONCLUSIONS: From our observations and from the
      evolution of dietary habits in France, it can be deduced that urolithiasis trends
      to a plateau.

PMID- 9032530
TI  - Double pigtail ureteric stent versus percutaneous nephrostomy: effects on stone
      transit and ureteric motility.
AB  - OBJECTIVES AND METHODS: The effects of double pigtail ureteric catheters (JJS)
      and percutaneous nephrostomies (PN) on ureteric motility and artificial stone
      transit was assessed in 12 dogs. Each animal underwent bilateral nephrostomies
      and an artificial stone insertion into each upper ureter (n = 20). A 4-Fr JJS was
      inserted on one side (group 1) while a PN was left on the contralateral side
      (group 2). In 4 stone-only 'control' ureters (group 3), the PN was sealed after
      72 h. Stone passage was assessed by plain x-rays. Pelvic and ureteric motility
      was assessed prior to stone insertion and again at 2 weeks. RESULTS: In group 1,
      only 1 of 8 stones (12.5%) passed completely. Four reached the midureter, 3
      remained static. Six of 8 stones (75%) in group 2 passed completely. Two stones
      remained in the distal ureter. All 4 stones (100%) in group 3 passed by day 3
      postoperatively. At laparotomy the J-stented ureters were dilated and both pelvic
      and ureteric contractions were diminished. Ureteric diameter was normal on the PN
      side. The ureters contracted with normal amplitude, but diminished rate of
      contraction above the stones in the ureters with residual calculi (n = 2), and in
      the 6 ureters from which spontaneous stone passage had occurred. A similar
      pattern was found in the 4 group 3 ureters. CONCLUSIONS: Double J stents are
      associated with ureteric dilatation, diminished peristalsis and impaired stone
      passage. APN preserves ureteric peristalsis and facilitates stone passage. In the
      initial phase, raised hydrostatic pressure appears to the most important factor
      determining stone passage.

PMID- 9032531
TI  - The value of antibiotic prophylaxis during extracorporeal shock wave lithotripsy
      in the prevention of urinary tract infections in patients with urine proven
      sterile prior to treatment.
AB  - INTRODUCTION: There are controversies in the literature regarding the need for
      and duration of antibiotic prophylaxis in patients treated with extracorporeal
      shock wave lithotripsy (ESWL) who have a negative urine culture before treatment.
      In order to determine the efficacy of antibiotic prophylaxis in ESWL treatment of
      patients with proven sterile urine, a randomized trial was performed. METHODS:
      Patients were randomized for placebo and 1 or 7 days antibiotic prophylaxis
      (cefuroxime or ciprofloxacin), starting 30 min before ESWL. Post-ESWL studies
      (immediately and 2 and 6 weeks after ESWL) included patient history, urine
      culture and Gram stain. RESULTS: After 2 weeks 20% of the patients and after 6
      weeks 23% of the patients had bacteriuria, but there was no statistical
      significance between patients treated with placebo or those receiving
      prophylactic treatment. Only 2-3% of the patients (in the prophylaxis and placebo
      group) had clinical and bacteriological signs of a urinary tract infection,
      either 2 or 6 weeks after ESWL, possibly caused by re-infection, however, since
      bacteria were found in none of the urine samples collected directly after ESWL.
      There was no beneficial effect of antibiotic prophylaxis, in the prevention of
      urinary tract infections in patients with a nephrostomy catheter or dilatation at
      the site of treatment. CONCLUSION: We conclude that in patients with urine proven
      sterile prior to ESWL there is no need for antibiotic prophylaxis.

PMID- 9032532
TI  - Transurethral ureteroscopy: is local anesthesia with intravenous sedation
      sufficiently effective and safe?
AB  - OBJECTIVE: To evaluate the effectiveness and safety of local anesthesia and
      sedation in ureteroscopic interventions and to compare the results with other
      kinds of anesthesia. METHODS: 107 ureteroscopic interventions have been done to
      99 renoureteral units involving 77 patients under different kinds of anesthesia.
      RESULTS: 45 of 107 procedures were performed under general anesthesia, 11 under
      spinal/epidural anesthesia, and 51 using local anesthesia and intravenous
      sedation. The overall success rate was 90%. The failure rate was 18% for the
      procedures undertaken using local anesthesia. CONCLUSION: Local anesthesia in
      ureteroscopic interventions may be considered as a first choice because of almost
      similar success rates to other kinds of anesthesia: is has a low morbidity and
      low cost.

PMID- 9032533
TI  - Radical nephrectomy for renal cell carcinoma: long-term results and prognostic
      factors on a series of 328 cases.
AB  - OBJECTIVES: A series of 328 evaluable patients with renal cell carcinoma operated
      by radical transabdominal nephrectomy with regional lymphadenectomy was reviewed
      to assess the prognostic significance of various pathologic parameters (pT, N, M,
      G and venous involvement) and the value of lymphadenectomy and of surgery of
      venous tumor thrombus. PATIENTS AND METHODS: The complete charts of 328 patients
      with renal cell carcinoma available to follow-up, who were operated between 1970
      and 1993, were reviewed. All patients underwent transabdominal extrafascial
      nephrosurrenalectomy and in all but 14 metastatic ones a regional retroperitoneal
      lymphadenectomy was performed. Surgery of venous tumor thrombus was performed in
      79 patients. Life expectancy according to pT stage, pN stage, M stage, nuclear
      grade and venous involvement was calculated by means of the life tables method
      and differences in survival were evaluated by means of the log rank test.
      Correlation analysis and multivariate data analysis according to the Cox model
      were also performed. RESULTS: Overall survival of the 328 patients was 50.70% at
      5 years, 35.10% at 10 years and 29% at 15 years. At multivariate data analysis
      the most important prognostic factors is the presence of metastases (8% survival
      at 5 years and no patient surviving more than 7 years after surgery), tumor grade
      was the second prognostic factor and statistically significant differences were
      also found at life tables analysis among G1, G2 and G3 tumors. Local tumor stage
      was the third leading prognostic factor at multivariate data analysis and
      statistically significant differences were also found at life tables analysis.
      Nodal and venous involvement had only minor importance at multivariate data
      analysis although statistically significant differences were found at life tables
      analysis between the pN+ and the pN0 patients, also in the absence of venous
      involvement and distant metastases. Anyway survival of the pN + M0V0 patients was
      satisfactorily high (53.20% at 5 years, 39.10% at 10 years and 16% at 15 and 20
      years). In patients with venous involvement no differences in survival were
      observed depending on the level reached by the tumor thrombus; differences in
      survival were observed between patients with venous involvement alone (38%
      surviving at 5 and 10 years) and patients who also had nodal or distant
      metastases (5.20% at 5 years and 0% at 10 years). CONCLUSIONS: From the review of
      our series it seems that the most important prognostic factors are synchronous
      metastases, tumor grading and the completeness of tumor exeresis. In fact, the
      low impact on survival of nodal involvement by itself is probably due to the
      completeness of lymphadenectomy. The value of regional lymphadenectomy is
      sustained by the high long term survival of N + M0V0 patients. Regarding venous
      involvement, it seems that V+ patients free from nodal and distant metastases may
      benefit from radical surgery, which on the contrary has only minimal impact on
      survival of V+M+/N+ patients.

PMID- 9032534
TI  - Correlation between DNA ploidy, proliferation marker Ki-67 and early tumor
      progression in renal cell carcinoma. A prospective study.
AB  - OBJECTIVE: The course of metastatic renal cell carcinoma shows a broad range of
      interindividual variation that cannot be sufficiently predicted by tumor stage
      and grade. The aim of this study was to establish the prognostic value of DNA
      ploidy and the proliferation marker Ki-67 in renal cell carcinoma. METHODS: Both
      parameters were measured simultaneously in 100 tumors and then correlated with
      the classic prognostic criteria pathologic stage and tumor differentiation grade
      as well as clinical course (early tumor progression). RESULTS: DNA ploidy
      correlated well with staging, grading and early progression. The proliferation
      index (Ki-67) correlated well with tumor stage and histopathological grade but
      not with the clinical course (early progression). CONCLUSION: Due to the diverse
      biological potential of renal cell carcinoma observation of further clinical
      course, including late tumor progression, will be necessary to determine whether
      one of these two indicators can provide additional information beyond what
      differentiation grade and tumor stage already tell us.

PMID- 9032536
TI  - Treatment of patients with bladder exstrophy or incontinent epispadias. A long
      term follow-up.
AB  - OBJECTIVE: To determine the late outcome concerning urinary continence, late
      complications, sexuality, and fertility in patients with the exstrophy-epispadias
      complex. METHODS: Until July 1994, 115 patients underwent surgical treatment at
      our institution. The mean follow-up period in 102 patients is 16.7 years. Urinary
      diversion was performed in 88 patients, a modified Young-Dees procedure in 8, a
      sling plasty in 3, and genital reconstruction alone in 3 patients. RESULTS: The
      present continence rates are 96% for rectal reservoirs, 97% for Mainz pouch 1,
      and 67% for the modified Young-Dees procedure. The upper tracts have remained
      stable, and no bowel neoplasms have developed. 16 of 17 women > or = 18 years of
      age are satisfied with the cosmetic result after genital reconstruction. All
      adults engage in sexual intercourse; 5 women have delivered 7 children by
      cesarean section. 30 of 32 male adults are satisfied with the cosmetic result of
      the reconstructed external genitalia. Penile deviation was present in 11,
      distressing in 2 patients. After genital reconstruction 9 developed epididymitis,
      necessitating 2 orchiectomies and 3 vasectomies. No patient with reconstruction
      of the external genitalia can ejaculate normally or has fathered children,
      whereas the ejaculation was normal in 3 who did not undergo genital
      reconstruction. Furthermore, 2 of the 5 have fathered 4 children. CONCLUSIONS:
      Rectal reservoirs represent our urinary diversion of choice. After failed
      reconstruction/insufficient anal sphincter, a Mainz pouch I is constructed. The
      cosmetic results achieved by genital reconstruction are satisfactory. In women,
      antefixation of the uterus should be performed before or together with an
      introitus plasty to prevent uterine prolapse. In men, however, surgery is
      performed at the expense of fertility.

PMID- 9032535
TI  - Evaluation of urinary glycosaminoglycan excretion in patients with renal cell
      carcinoma.
AB  - OBJECTIVE: To evaluate a possible correlation between the urinary excretion of
      glycosaminoglycans (GAGs) and tumor stage and size in renal cell cancer (RCC), a
      prospective controlled study was performed. METHODS: 34 patients (13 females, 21
      males) with clinically and histologically proven RCC were included in the study.
      Following the staging procedures of RCC in each patient nephrectomy was
      performed; subsequently the size of the tumor (length and width) was calculated
      using nephrectomy material. Urinary GAG excretion was determined using a
      previously described method. RESULTS: Urinary GAG excretion was found to be
      increased in RCC patients, with a strong relation to the size of the tumor.
      Patients with relatively larger tumor masses seemed to excrete higher amounts of
      GAGs in urine (r = 0.8235; p < 0.001). In contrast, we were not able to show any
      significant difference in urinary GAG excretion with respect to tumor stage (f =
      5.92; p = 0.0068). Patients with multiple foci of RCC (n = 3) had relatively
      higher rates of GAG excretion than patients with same-size single-tumor masses.
      CONCLUSIONS: Although our results revealed GAG excretion in RCC patients as a
      possibly useful marker with respect to tumor size, no correlation to the stage of
      RCC was observed. Further investigation using larger series of patients and other
      definitive parameters is certainly needed in order to provide more reliable data,
      before considering urinary GAG excretion as a useful marker.

PMID- 9032537
TI  - The vanishing testis: anatomical and histological findings.
AB  - OBJECTIVES: To review anatomical and histological findings in 105 vanishing
      testes. METHODS: Records of 2,509 boys with 3,064 cryptorchid testes treated at
      our hospital between 1969 and 1995 were reviewed. RESULTS: 691 (23%) testes were
      clinically impalpable. Exploration in 691 impalpable testes revealed absent
      testis in 144 (21%). In 39 (27%) of the 144 absent testes, there was complete
      agenesis of testis along with the epididymis and vas deferens whereas 105 (73%)
      were associated with blind-ending cord structures-the vanishing testis. The site
      of blind-ending cord structures in 105 vanishing testes was intra-abdominal in 22
      (21%), inguinal canal in 62 (59%), superficial inguinal ring in 19 (18%) and
      scrotum in 2 (2%). Histological information was available in 47 vanishing testes
      and revealed vas, epididymis, or both in 32 (68%), fibrous/vascular tissue in 11
      (23%) and testicular cords in 4 (9%). Dystrophic calcification and/or
      haemosiderin were present in 7 (15%). CONCLUSIONS: Our data show that the
      incidence of vanishing testis in boys with non-palpable testes is over twice the
      incidence of testicular agenesis. The most common site of blind-ending cord
      structures is distal to the internal inguinal ring. The finding of viable
      testicular tissue at the end of the attenuated cord structures in 4 of our
      patients, and also reported in other series, suggests that inguinal exploration
      should be carried out in all patients who on laparoscopy are found to have cord
      structures entering the internal ring.

PMID- 9032538
TI  - Bladder rehabilitation, the effect of a cognitive training programme on urge
      incontinence.
AB  - OBJECTIVE: To assess the effectiveness of a 10-day inpatient treatment programme
      for persistent urge incontinence based on behavior modification via biofeedback
      of micturition behavior. METHODS: 95 patients aged 6-17 (86 girls, 9 boys) with
      documented and persistent urge incontinence, with or without dysfunctional
      voiding, mostly based on recurrent urinary tract infections, and at least a 1
      year lasting failure of standard regimen and pharmacological therapy, were
      'cognitively' treated. After 6 months the patients were evaluated for flow
      pattern, number of wet incidents, micturition frequency and urge compliants.
      RESULTS: 65 patients (68.4%) obtained good results, 12 (12.6%) showed average
      improvement, 18 patients (19%) did not improve. CONCLUSIONS: This cognitive
      noninvasive treatment programme seems promising in its effectiveness and compares
      favorably with existing biofeedback methods based on urodynamic procedures,
      although expensive by its inpatient status. Further study towards an outpatient
      implementation is needed.

PMID- 9032539
TI  - Clinical significance of immunohistochemically detectable p53 protein in renal
      cell carcinoma.
AB  - OBJECTIVE: To elucidate the clinical significance of p53 protein in renal cell
      carcinoma (RCC). MATERIALS AND METHODS: The p53 protein in the paraffin-embedded
      materials taken from 72 patients with RCCs was evaluated immunohistochemically
      and was compared with the histological findings, expression of proliferating cell
      nuclear antigen (PCNA), genetic instability as assessed by 2c deviation index
      (2cDI) and 5c exceeding rate (5cER) as well as clinical outcome. RESULTS: The p53
      positivity was demonstrated only in a localized and/or focal area of the
      cancerous tissue. The positive rate of p53 protein was 40.3% in this study. The
      p53 protein significantly correlated with nuclear grade as well as PCNA
      expression (p < 0.001 and p < 0.01, respectively). Although there was a wide
      scatter of 2cDI and 5cER values between p53 positive and negative RCCs, the RCC
      with positive p53 exhibited significantly higher values in 2cDI as well as 5cER,
      as compared to that with negative p53 (p < 0.02 and p < 0.005, respectively).
      However, some of the RCCs with negative p53 showed relatively higher values in
      2cDI and 5cER. Using univariate analysis, the prognostic relevance was noted in
      T, N, M categories, age and p53 positivity, while it was not in 2cDI, 5cER and
      PCNA expression. Multivariate analysis demonstrated that N category and p53
      positivity were independently significant indicators in predicting survival.
      CONCLUSIONS: The presence of p53 protein might reflect the genetic instability
      already occurred. The p53 positivity reflecting a high cellular proliferation
      could afford an additional but useful information when predicting survival in
      patients with RCC.

PMID- 9032540
TI  - The 72nd codon change of p53 in primary renal cell carcinoma was confirmed as a
      polymorphism among Japanese.
AB  - OBJECTIVE: The role of p53 mutation in renal cell carcinoma (RCC) is not fully
      understood particularly among Japanese, although frequent loss of heterozygosity
      (LOH) has been demonstrated at polymorphic exon 4. METHODS: We examined the p53
      gene in 43 primary RCC samples by polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) analysis for exons 4-9 and restriction
      fragment length polymorphism (RFLP) analysis. RESULTS: In PCR-SSCP analysis, no
      apparent mobility shift was observed regardless of the clinical stage of the
      disease, histological subtype or malignancy grade of the tumor. In RFLP analysis,
      none of 13 informative cases showed gross alteration of the gene. CONCLUSION: We
      conclude that mutations of the p53 gene are not major events in the development
      and progression of RCC among Japanese.

PMID- 9032541
TI  - A flow cytometric analysis of the expression of adhesion molecules on human renal
      cell carcinoma cells with different metastatic potentials.
AB  - OBJECTIVES: We investigated the relationship between the metastatic potential and
      the surface expression of adhesion molecules on human renal cell carcinoma (HRCC)
      cells. METHODS: The metastatic potential was studied by the intravenous injection
      of cells from an HRCC cell line SN12C parent and its variants, SN12C-MM3, SN12C
      clone2 and SN12C-clone8 into athymic Balb/c nude mice. The surface expression of
      adhesion molecules on these four HRCC cell lines was studied by a flow cytometric
      analysis. RESULTS: Of the four cell lines, SN12C-MM3 had the highest ability to
      produce pulmonary metastatic nodules. In contrast, the SN12C parent, SN12C-clone2
      and SN12C-clone8 produced either few or no pulmonary metastatic nodules. A flow
      cytometric analysis revealed that SN12C-MM3 showed a strong expression of sialyl
      Lewis X (sialyl Le(x)) carbohydrate antigen and a slightly stronger expression of
      CD11a (LFA-1 alpha-chain) and CD54 (ICAM-1) compared with the other three cell
      lines. All cell lines expressed CD29 (beta 1-integrin) and CD44 to the same
      extent. CONCLUSION: Sialyl Le(x) is thought to be a ligand for the adhesion
      molecule called ELAM-1 (endothelial-leukocyte adhesion molecule-1, E-selectin)
      and mediates the interaction of leukocytes or tumor cells to endothelial cells,
      followed by the integrin-mediated adhesion. These data suggest that SN12C-MM3
      cells may have more of a chance to adhere to endothelial cells in blood vessels
      and consequently shows a higher metastatic potential when injected intravenously
      in comparison to the other three lines.

PMID- 9032542
TI  - Antitumor effect of CPT-11, a camptothecin derivative, on human testicular tumor
      xenografts in nude mice.
AB  - OBJECTIVE: The antitumor effect of CPT-11, a camptothecin derivative, on two
      human testicular embryonal carcinomas (TTSC-2 and TTSC-3) heterotransplanted into
      nude mice was studied. MATERIALS AND METHODS: Tumor-bearing nude mice were given
      daily intraperitoneal injections of the anticancer drugs in 0.1 ml saline 3 times
      at 3-day intervals. At the end of the experiments tumors were resected and
      subjected to light-microscopic observation. RESULTS: When 10, 30 and 50 mg/kg of
      CPT-11 was administered to tumor-bearing mice intraperitoneally, the antitumor
      effect of CPT-11 was observed dose-dependently in both TTSC-2 and TTSC-3. When 30
      mg/kg of CPT-11 was administered in combination with CDDP, complete tumor
      regression was observed in both TTSC-2 and TTSC-3 tumors. Histological findings
      correlated well with the decrease in tumor volume of treated tumors. No mice died
      after treatment with CPT-11 in a single-agent and combination chemotherapy.
      CONCLUSION: Chemotherapy with CPT-11 was an effective and safe method against
      human testicular tumors heterotransplanted in nude mice.

PMID- 9032543
TI  - Enzyme activities in tissue of human benign prostatic hyperplasia after three
      months' treatment with the Sabal serrulata extract IDS 89 (Strogen) or placebo.
AB  - OBJECTIVE: The mechanism of action of plant extracts used for the medical
      treatment of human benign prostatic hyperplasia (BPH) is still unknown. In this
      prospective, randomized, double-blind trial, we investigated the possible
      influence of the Sabal serrulata extract IDS 89 (Strogen) on epithelial and
      stromal enzyme activities of BPH tissue. METHODS: 18 patients with BPH were
      randomly assigned to receive 3 x 2 capsules Strogen uno (320 mg/capsule) (n = 8)
      or placebo (n = 10) daily for 3 months. The activity (Vmax and Km) of 5 alpha
      reductase. 3 alpha-HSORred, 3 beta-HSORred, and creatine kinase was determined in
      mechanically separated epithelium and stroma of human BPH. RESULTS: The
      multivariate correlation analysis revealed a positive correlation between therapy
      and the following enzyme alterations: (1) In epithelium, the substrate affinity
      of the 5 alpha-reductase decreased slightly (increase of Km value). (2) In
      stroma, the Vmax value of the 3 alpha-HSORred increased statistically distinctly,
      leading to a moderate increase of Vmax/Km. (3) In stroma, the Vmax value of the 3
      beta-HSORred increased moderately, but not statistically significant. (4) In
      stroma, the Vmax value of creatine kinase increased significantly, leading to a
      statistically distinct increase of Vmax/Km. CONCLUSION: This double-blind,
      placebo-controlled clinical trial with the S. serrulata extract IDS 89 revealed
      significant biochemical changes at the cellular level of BPH tissue. However, the
      alterations are merely moderate, their biochemical causes and consequences
      regarding the pathophysiology of BPH rather uncertain. Therefore, more studies
      are needed before plant extracts like IDS 89 become valid candidates likewise
      synthetic substances already used for medical treatment of human BPH.

PMID- 9032544
TI  - Intussuscepted partial-thickness ileal valve in continent urinary diversion.
AB  - OBJECTIVE: This study was undertaken to ascertain the feasibility of fashioning a
      nipple valve from partial-thickness ileum and to assess the competence and
      durability of that valve. The approach employed was designed to circumvent the
      necessity for considerable lengths of bowel to be committed to valve formation
      and to avoid the tendency for desusception, present with other forms of nipple
      valves. METHODS: A technique in which a subterminal segment of partial-thickness
      ileum was 'skinned' circumferentially of serosa and muscularis propria and then
      intussuscepted to form a continent nipple-valve mechanism was studied for up to 4
      months in 10 dogs. The intussuscepted partial-thickness ileal valve was in
      continuity with a terminal ileal segment sutured flush with skin and, internally,
      with another segment laid open and anastomosed to the bladder. RESULTS: All
      valves were competent, withstanding intravesical pressures up to 90 cm H2O. Six
      dogs were catheterized, without difficulty, twice daily up to 104 days. The valve
      mucosal surfaces were smooth due to a loss of plicae circulares, and, between
      'back-to-back' submucosal layers, a fine stroma developed. CONCLUSIONS: This
      simple technique, which is frugal in its use of bowel, provided a robust and
      effective ileal continence mechanism. Furthermore, because of denervation and
      interposing fibrous tissue, this nipple valve is considered most unlikely to
      desuscept subsequently. The intussuscepted partial-thickness ileal valve approach
      is recommended now for clinical evaluation.

PMID- 9032545
TI  - Ultrastructural mucosal appearance in the ileal neobladder.
AB  - METHODS: 15 patients with ileal neobladder underwent endoscopic biopsy at
      different postoperative intervals. The specimens were analyzed by electron
      microscopy in order to evaluate the evolution of the mucosal changes
      ultrastructurally. RESULTS: No significant change was observed 3 months after the
      operation. After 6 months, the number and height of the microvilli were reduced,
      the cell borders crooked and the terminal web upset. After 12 months
      disappearance of the glycocalyx, increased lysosomal features, increased activity
      of the muciparous cells, rounded mitochondria and loss of the polarized
      disposition of the cytoplasmic organelles were detected in the enterocytes. We
      observed no other substantial change after 24 months and more. CONCLUSIONS:
      Progressive modifications occur in the cytoplasmic structures involved in the
      absorptive process. They do not seem to begin before 3 months and are almost
      totally completed after 1 year.

PMID- 9032546
TI  - Arteriovenous fistula following nephrectomy.
AB  - Arteriovenous fistula (AVF) of the renal pedicle is a rare complication of
      nephrectomy. Since the 1st case report in the literature, 62 cases have been
      reported in the world literature. A continuous abdominal or lumbar bruit is
      diagnosed. They may also present with symptoms of congestive heart failure and/or
      hypertension. METHODS: 37 years following nephrectomy, a case of AVF of the right
      renal pedicle associated with gross proteinuria is described. RESULTS: The
      clinical diagnosis was confirmed by aortogram, and the proteinuria subsided after
      successful surgical management. CONCLUSION: The causes of proteinuria may be due
      to the hyperfiltration state. To our knowledge, there has been no previous report
      of this combination in the literature.

PMID- 9032547
TI  - Treatment of dual urinary and fecal incontinence by implantation of two AMS 800
      artificial sphincters. Case report.
AB  - We report the case of a 61-year-old woman with urinary and anal incontinence due
      to neurologic disease. An AMS 800 artificial sphincter was implanted first round
      the bladder neck with recovery of satisfactory urinary continence. Four months
      later, another AMS 800 artificial sphincter was implanted round the anal
      sphincter. Two revisional procedures had to be performed: replacement of the pump
      for mechanical failure, and replacement of the low-pressure balloon by a high
      pressure one. Finally the patient has been almost completely continent with only
      occasional leakage of feces or liquid stools (follow-up 24 months after
      activation). Defecography shows total rectal evacuation and anorectal manometry
      records an anal closing pressure of 70 cm H2O. Dual implantation of artificial
      sphincters is possible for incontinence of neurological origin, provided bladder
      and rectal compliance are normal.

PMID- 9032548
TI  - Direct invasion of the renal vein by metastatic testicular cancer.
AB  - We report a case of metastatic seminoma with direct invasion of the left renal
      vein. A tumor thrombus was found in the renal vein while the vena cava thrombosis
      proved to be a noncancerous blood clot developing as an extension of the tumor
      thrombus. Primary chemotherapy could not be completed because of thrombotic
      growth requiring surgical intervention. Although surgical specimens were free of
      viable tumor and two cycles of adjuvant chemotherapy were applied, the tumor
      relapsed in the area of renal vein invasion.

PMID- 9032549
TI  - Malignant pheochromocytoma of the bladder: current controversies.
AB  - Urinary bladder pheochromocytoma is an uncommon tumor that produces hypertensive
      crises coinciding with micturition. It is usually benign, with less than 20 cases
      with evidence of metastasis described to date. We present a rare case of a
      malignant bladder pheochromocytoma with regional metastasis, where the
      pathological and scintigraphic findings are described. The controversy about
      pathology diagnosis, treatment and prognosis of this unusual tumor is discussed.

PMID- 9032550
TI  - The treatment of vesicovaginal fistulae.

PMID- 9032551
TI  - Longitudinal evaluation of prostate-specific antigen levels in a case-control
      study.

PMID- 9032562
TI  - Action of vasopressin in superfused human granulosa cells in vitro.
AB  - Arginine-vasopressin as well as luteinizing hormone (LH)/follicle-stimulating
      hormone (FSH) stimulate progesterone release in superfused human granulosa cells.
      Extracellular administration of inositol triphosphate (10(-6) mol/l) or calcium
      ions (10(-4) mol/l) mimics the action of both arginine-vasopressin and LH/FSH and
      evokes progesterone secretion in superfused granulosa cells.

PMID- 9032563
TI  - Vascular endothelial growth factor messenger ribonucleic acid expression in human
      ovarian and endometrial cancer.
AB  - Vascular endothelial growth factor (VEGF) is a previously discovered angiogenic
      factor that seems to influence the neoangiogenesis of neoplastic and non
      neoplastic tissues. Substantial experimental evidence links tumor growth and
      metastasis with blood vessel formation. Tumor angiogenesis can be induced by
      factors released by the tumor cells themselves. A variety of transformed cell
      lines expresses the VEGF transcript and secretes an EGF-like protein, suggesting
      that this angiogenic factor may be one of the mediators of tumor angiogenesis. By
      Northern blot analysis and in situ hybridization, we investigated the expression
      of VEGF transcript in human ovarian and endometrial neoplasms. Messenger RNA
      encoding VEGF was detected in all tissues studied and was more densely expressed
      in endometrial carcinoma. VEGF expression was also identified in cells obtained
      from ovarian and endometrial ascitic fluid. VEGF mRNA, detected by in situ
      hybridization, was identified in the epithelial cells of endometrial
      adenocarcinoma. This distribution was localized primarily in the apices of the
      papillae. The prominence of VEGF mRNA levels in human ovarian and endometrial
      tumors demonstrates that VEGF may be involved in promoting tumor angiogenesis and
      stroma generation, acting as an endothelial cell mitogen.

PMID- 9032564
TI  - Changes in pituitary response to gonadotropin-releasing hormone following
      bilateral ovariectomy in women treated with follicle-stimulating hormone.
AB  - Superovulation- induction in women attenuates the pituitary response to
      gonadotropin-releasing hormone (GnRH). The aim of this study was to assess the
      duration of the suppressing activity of the ovaries on the pituitary. Eighteen
      normally ovulating women received treatment with follicle-stimulating hormone
      (FSH, 225 IU/day) on cycle days 2, 3 and 4. On cycle day 4, six women underwent
      hysterectomy plus bilateral ovariectomy (group A), another six women underwent
      hysterectomy without ovariectomy (group B) and the remaining six women underwent
      no operation (group C). The women of group C were also investigated during a
      preceding untreated spontaneous cycle (group D). The response of luteinizing
      hormone (LH) to an intravenous injection of 10 micrograms GnRH was investigated
      on cycle days 2, 3, 4 (2 and 12 h after clamping of the infundibulopelvic and/or
      round ligaments), 5, 6 and 7 in all four groups. The response of LH to GnRH at 30
      min (delta LH) was significantly attenuated as early as 12 h from the onset of
      FSH treatment (groups A, B and C), while estradiol and inhibin concentrations
      started to increase later (group C). In group C (no operation), the attenuation
      of delta LH values continued throughout the study period, while in groups A and B
      the initial attenuation was followed by a marked increase in delta LH values
      within 2 h from the operation. The increase in group A was twice the value in
      group B. Following this, delta LH values in group B were attenuated again within
      the next 24 h, while in group A they remained for the rest of the postoperative
      period significantly higher than in group B. In conclusion, it was found that the
      factor that mediates the suppressing effect of superovulated ovaries on the
      pituitary has a short-lasting (< 2 h) attenuating activity in the circulation.

PMID- 9032565
TI  - Nasal spray administration of bromocriptine: pharmacology and effect on serum
      prolactin level in puerperal women.
AB  - This study was aimed at investigating the absorption of nasally administered
      bromocriptine and its effect on serum prolactin level. Fifteen physiologically
      hyperprolactinemia women who had asked to discontinue breast feeding received a
      single nasal spray administration of 0.8 mg bromocriptine. Serum prolactin levels
      were measured by radioimmunoassay at 30 and 15 min before drug administration, at
      the time of administration and at 15, 30, 60, 120, 240, 480 and 720 min after
      administration; bromocriptine was radioimmunoassayed in only five of the patients
      from time 0 to 720 min after administration. Serum bromocriptine levels increased
      rapidly after administration, reached a maximum at 120 min and thereafter
      declined slowly over the subsequent 10 h. As the bromocriptine level increased
      there was a decline in the serum prolactin level. The first significant decline
      in serum prolactin level compared with the baseline level occurred at 30 min
      after administration and the level continued to decrease significantly until time
      120 min. Four hours after administration the mean serum prolactin level was
      within the normal assay range. The maximum decline in serum prolactin level was
      reached at 720 min after administration. Correlation analysis between serum
      bromocriptine and prolactin concentrations yielded a significant negative value
      between times 0 and 120 min after administration. There was no significant change
      in mean orthostatic systolic or diastolic blood pressure or in mean heart rate.
      Only one patient complained of headache and dizziness; another experienced mild
      transient nausea, and none had vomiting. Ten patients (66.67%) reported light
      endonasal burning and an unpleasant taste which subsided after a few minutes; no
      patient showed nasal irritation at nasal examination. In conclusion, nasal
      administration of 0.8 mg bromocriptine was effective in reducing the serum
      prolactin level for more than 12 h after administration without inducing
      significant side-effects.

PMID- 9032566
TI  - A study of the clinical differences between women and men with
      hyperprolactinemia.
AB  - A group of 64 women and 14 men with hyperprolactinemia were followed up in an
      endocrine service center for a mean of 43 months. The various parameters in each
      sex were compared. The mean age at first visit was 49 years in the men and 36
      years in the women (p < 0.001). The peak prolactin index levels were 13.7 in the
      men and 5.5 in the women (p < 0.002). Macroprolactinomas were significantly more
      prevalent in the men (p < 0.002). The women complained significantly more about
      headache (p < 0.02), malaise (p < 0.02), restlessness (p < 0.03) and fatigue (p <
      0.04). These symptoms had no correlation with the prolactin level. Thus, in the
      men the clinical manifestations of hyperprolactinemia came to attention at an
      older age and had a connection with a higher prevalence of macroprolactinoma. The
      possible mechanisms are discussed. Vague complaints, reported more often by the
      women, do not seem to correlate with the prolactin level.

PMID- 9032567
TI  - Parameters that influence the results of in vitro fertilization/embryo transfer:
      a study of an egg donation model.
AB  - A retrospective analysis was carried out after ovulation induction in donors, and
      treatment outcome in donors and recipients, relating to variables such as: age,
      protocol of ovarian stimulation, transfer of fresh or cryopreserved embryos,
      number of embryos transferred including quality and etiology of donor and
      recipient infertility. The recipients underwent 214 cycles of embryo transfer
      from 82 different donors. Forty-five (21%) pregnancies were recorded. The age of
      the recipients significantly affected the conception rate (pregnancy rate of 30%
      in those aged < 30 years, compared to 9.7% in those aged > 44 years) and the
      donors were contributed more to pregnancies were also younger. The pregnancy rate
      was significantly higher when fresh embryos were transferred to recipients (28%,
      compared to 15% when cryopreserved embryos were transferred). In addition, the
      number of embryos transferred affected the pregnancy rate if > or = 3 embryos
      were transferred and, if they were of good quality, the success was significantly
      higher. Ultimately, when the ovarian stimulation protocol was clomiphene citrate
      and human menopausal gonadotropin or gonadotropin-releasing hormone
      agonist/follicle-stimulating hormone/human menopausal gonadotropin, and the
      etiology of infertility was polycystic ovarian disease in the donors, the success
      rate was significantly increased in the recipients.

PMID- 9032568
TI  - The relationship between insulin sensitivity and insulin-like growth factor
      binding protein-1.
AB  - Insulin has been shown to regulate insulin-like growth factor-binding protein-1
      (IGFBP-1) in vivo and in vitro. Insulin resistance is a feature of the polycystic
      ovary syndrome (PCOS). We have studied the relationship between insulin
      sensitivity (S1) and the circulating concentration of IGFBP-1 in a group of young
      women and in some who had PCOS. A case-control study has been carried out
      comparing reproductively normal women with women with PCOS (defined as women with
      oligo- or amenorrhea associated with androgen excess). Fifteen women with
      clinical PCOS and ten age- and weight-matched controls were studied. S1 was
      measured by the frequently sampled intravenous glucose tolerance test (FSIGT)
      using the minimal model technique. IGFBP-1, insulin-like growth factor-I (IGF-I)
      and growth hormone levels were measured before and during the FSIGT. Circulating
      testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels were
      measured while the subjects were fasting. S1 and IGFBP-1 levels were
      significantly lower in the PCOS group than in controls (S1/10(-5) min-1/pM] mean
      +/- SE 3.8 +/- 0.8 vs. 8.5 +/- 1.3, p < 0.03; IGFBP-1 [ng/ml] mean +/- SE 26.6 +/
      4.2 vs. 56.0 +/- 5.9, p < 0.005). In women with PCOS, IGFBP-1 concentrations
      related negatively to the body mass index (BMI) (r = -0.77, p < 0.003) and
      positively to S1 (r = 0.76, p < 0.003). S1 remained a significant predictor of
      IGFBP-1 concentrations when controlled for BMI (combined r2 = 0.35, p < 0.05). No
      relationship was found between androgen levels and IGFBP-1. Insulin sensitivity
      contributed to the difference in IGFBP-1 levels found in women with PCOS. Whether
      the reduced concentrations of IGFBP-1 play a role in the pathophysiology of PCOS
      is uncertain, but it may act to alter delivery of IGF to peripheral tissues in
      insulin-resistant individuals.

PMID- 9032569
TI  - Comparative effects on bone mineral density of tibolone, transdermal estrogen and
      oral estrogen/progestogen therapy in postmenopausal women.
AB  - The aim of the study was to assess the comparative effects on bone mineral
      density (BMD) in routine clinical practice of tibolone and estrogen (given either
      unopposed or combined with cyclical progestogen) in postmenopausal women who had
      not previously received estrogen or other menopausal therapy. BMD was measured in
      the spine and hip by dual energy X-ray absorptiometry (DEXA) at 12-month
      intervals over 3 years in 82 consecutive postmenopausal women referred for
      climacteric therapy. Of these, 35 women received tibolone, 24 transdermal
      estradiol alone and 12 conjugated equine estrogens together with cyclical
      progestogen; 11 received no therapy other than calcium. BMD increased
      significantly in the spine in those taking tibolone over 3 years (p < 0.0001 at 1
      year; p < 0.0001 at 2 years; and p = 0.03 at 3 years). In those treated with
      conjugated equine estrogens and cyclical progestogen, BMD in the spine also
      increased significantly over the first 2 years (p = 0.03 at 1 year; p = 0.004 at
      2 years), but not at 3 years. However, although BMD in the spine also rose over 3
      years in the women treated with transdermal estradiol alone, the increase was not
      statistically significant. No significant change in the BMD of either the spine
      or the hip was observed in the control group. A significant difference in the
      increase of BMD in the spine between the different treatment groups was observed
      at 2 years (p = 0.004) in favor of those taking tibolone or conjugated equine
      estrogens, compared to women who received transdermal estradiol. The highest
      proportion of individual responders to therapy after 2 years' treatment was
      observed in those receiving tibolone or conjugated equine estrogens. There was no
      significant change in the BMD of the hip over 3 years, irrespective of the
      therapy taken, although there was a tendency towards a progressive increase in
      the women on tibolone. Neither the age of the women, their body mass index or
      pretreatment BMD had a significant effect on changes in bone density. Since
      tibolone effected a greater increase in spine BMD than did either conjugated
      equine estrogen with progestogen or transdermal estradiol alone, it is
      particularly suitable for older women who often have more advanced osteoporosis
      and who would not accept a return of cyclical bleeding.

PMID- 9032570
TI  - Further data favoring the hypothesis of the uterine first-pass effect of
      vaginally administered micronized progesterone.
AB  - Ten infertile women, 28 to 36 years of age, with regular menstrual cycles were
      treated with oral estradiol valerate and intravaginally administered micronized
      progesterone under pituitary suppression with leuprolide acetate. Patients
      underwent endometrial biopsies on cycle days 17 and 28 (luteal phase days 3 and
      14) and blood sampling for plasma progesterone and estradiol determinations on
      cycle days 17, 21 and 26 (luteal phase days 3, 7 and 12). All ten endometrial
      biopsies on cycle day 17 were in-phase and only two out of ten (20%) were out-of
      phase on cycle day 28. This produced an incidence of endometrial luteal phase
      deficiency that was not different from the 14% found among an infertile general
      population of 300 women. Midluteal estradiol plasma levels in the study group
      were similar to those found in a control group of fertile women, but progesterone
      levels were significantly lower on cycle day 21 in the treatment group. As much
      as 75% (six out of eight patients) of treated women having in-phase late luteal
      endometrial biopsies had low midluteal plasma progesterone levels, a situation
      that is found in only 3% of infertile patients (9/300) or 3.5% (9/258) of those
      infertile women with normal endometria (p = 0.03). Thus, the present study adds
      further evidence favoring the current postulate that vaginal micronized
      progesterone enhances hormone delivery to the uterus and this explains the marked
      discrepancy between the strong uterine effect and the relatively low plasma
      progesterone levels.

PMID- 9032571
TI  - Polycystic ovary syndrome: the present position.
AB  - This article discusses two areas that have seen progress in our understanding and
      management of women with polycystic ovary syndrome. The first relates to factors
      responsible for clinical expression of the disorder, the second to the management
      of infertility by surgical methods. These two areas have been chosen partly
      because of their intrinsic importance and partly because they indicate the
      breadth of work being pursued by investigators and clinicians in this field.

PMID- 9032572
TI  - NSAID gastropathy: state of the art.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) give rise to a wide range of
      gastrointestinal side-effects. These are reviewed and it is stressed that some
      safety measures are possible only if the risk factors are considered. The
      relations between dyspeptic symptoms and gastrointestinal lesions are also
      debated. It is suggested that the ulcerogenic potential of various molecules must
      be carefully evaluated, especially in elderly patients.

PMID- 9032573
TI  - Epidemiological aspects of NSAID gastropathy.
AB  - NSAIDs are among the most frequently prescribed drugs worldwide. Unfortunately
      acute and especially chronic NSAID intake is accompanied by untoward side effects
      of the digestive system, particularly the gastroduodenal tract. Erosions and
      ulcers are more common in the stomach, but also the duodenal mucosa can be
      involved. Elderly patients are the subjects most at risk of developing gastric
      lesions, which are often asymptomatic. Complications such as bleeding and
      perforation may suddenly occur, sometimes with a fatal outcome. Epidemiological
      data and risk factors are reviewed and commented in detail.

PMID- 9032574
TI  - Endoscopic aspects of gastroduodenal mucosa due to NSAIDs.
AB  - The role of endoscopy in NSAID-related gastroduodenal pathologies is reviewed. If
      an accepted and largely used algorithm in which the role of endoscopy is exactly
      identified is not available, current strategy for the management of
      gastroduodenal toxicity gives indication for endoscopy immediately after the
      onset of symptoms, anaemia and evidence of bleeding, overt or occult. The
      endoscopic patterns of lesions in patients taking NSAID are characteristics
      patterns of erosive and ulcerative lesions. Endoscopy can recognize early
      lesions, allowing us to prevent a more advanced mucosal damage.

PMID- 9032575
TI  - Histopathological aspects of mucosal injury related to non-steroidal anti
      inflammatory drugs.
AB  - As the majority of patients with chronic arthritis are treated, for many years,
      with non-steroidal anti-inflammatory drugs (NSAID), it is only natural to expect
      the long-term use of these agents to be associated with a range of oesophago
      gastro-duodenal histopathological changes. We have demonstrated that oesophagitis
      (defined as basis of papillary length, basal cell hyperplasia and inflammatory
      cell infiltration) is less prevalent in patients taking NSAID. This phenomenon
      can be utilised in the treatment of certain conditions such as post-irradiation
      oesophagitis and Barrett's oesophagitis. It also implies that NSAID-related
      oesophageal ulceration is due to lodging of tablets in the oesophagus and is, in
      turn, preventable by swallowing of some fluids or solids after taking NSAID. In
      the stomach, long-term use of NSAID is associated with a specific entity known as
      chemical or reactive gastritis in about 25% of cases. This is frequently
      associated with ulceration. Chronic active superficial gastritis, in the presence
      of Helicobacter pylori, can be found in about 70% of cases. Not unlike
      oesophagitis, the prevalence of active duodenitis is low in chronic NSAID users.
      Local ulceration still takes place. This implies that duodenitis is not required
      in at least some cases of NSAID-related duodenal ulcers, and demonstrates the
      multi-factorial nature of the pathogenesis of mucosal damage in long-term users
      of a NSAID.

PMID- 9032576
TI  - Ultrastructural damage of gastric epithelium in patients taking NSAIDs.
AB  - As far as concerns ultrastructural lesions in the gastric epithelium following
      NSAIDs, a review has been made of existing data and ideas for future research
      concerning the ultrastructural field are advanced. Specific ultrastructural
      damage of the gastric epithelial cells has been recognized in patients taking
      NSAIDs: this pattern of damage appears characterized by a proliferative phenomen
      of "desquamation" of contiguous epithelial cells. Studies in animal models
      indicate that the first-level of epithelial damage involves a mitochondrial
      derangement and an alteration of tight junctions and cytoskeletal. The length of
      time of local drug action on the gastric mucosa could be the reason for the
      characteristic morphological presentation seen in vivo. If ulcers are the result
      of an imbalance between cell necrosis and cell regeneration, the high progression
      speed of cell necrosis to contiguous cells should play a basic role in the
      genesis of ulcers.

PMID- 9032577
TI  - Early pathogenic events in NSAID-induced gastrointestinal damage.
AB  - A number of studies show that the idea that inhibition of cyclooxygenase is the
      sole mechanism of NSAID-induced gastrointestinal damage is no longer tenable. We
      re-examined various aspects of the mechanism of small intestinal damage due to
      NSAIDs in rat. Subcellular organelle marker enzyme studies show selective
      alterations in mitochondrial and brush border marker enzymes. Electron microscopy
      shows changes compatible with uncoupling of mitochondrial oxidative
      phosphorylation. In vitro, all common acidic-NSAIDs (n = 15) were found to
      uncouple oxidative phosphorylation at concentrations (microM) easily achievable
      within intestinal epithelium. Experiments in bile duct ligated animals show that
      intact indomethacin within the gastrointestinal lumen is required for uncoupling.
      Relative importance and pathophysiological consequences of uncoupling and
      inhibition of cyclooxygenase were assessed following administration of R and S
      flurbiprofen: the former selectively uncouples whilst the latter is also an
      effective cyclooxygenase inhibitor. R flurbiprofen uncoupled in vitro and in
      vivo, increased intestinal permeability and caused mild intestinal inflammation,
      but had not significant effect on prostanoid levels and produced no ulcers. S
      flurbiprofen uncoupled and increased intestinal permeability equally but was
      associated with significant decreases in intestinal prostanoid levels, more
      inflammation and numerous ulcers. Collectively these studies suggest that
      uncoupling may underlie the "topical" phase of NSAID damage which leads to
      increased intestinal permeability and inflammation, but concomitant inhibition of
      cyclooxygenase is essential to drive the inflammation to ulcers.

PMID- 9032578
TI  - New directions in cyclooxygenase research and their implications for NSAID
      gastropathy.
AB  - The observations reported in this paper have led to the formulation of a new
      hypothesis concerning the action of NSAIDs updating the concept first put forward
      in the early 70's. The new paradigm is that COX 1, a constitutive enzyme is
      thought to be a housekeeping protein, and to be important in generating
      prostaglandins necessary for physiological purposes, amongst which may be
      suppression of gastric acid secretion. In contrast, the induced COX 2 enzyme
      appears mainly after cell injury and inflammation and is responsible for
      generating the prostaglandins which mediate inflammatory episodes. In this model,
      inhibition of COX 1 is thought to produce the undesirable side effects of NSAID
      therapy, whereas inhibition of COX 2 is thought to be responsible for the anti
      inflammatory effects. COX 2, therefore, appears to be the enzyme that should be
      targeted in anti-inflammatory drug therapy. By designing or screening for
      specific COX 2 inhibitors, it should be possible to develop drugs which are at
      least as effective anti-inflammatory agents as the current NSAIDs, but that are
      much safer in terms of gastrointestinal and other side effects. Early preclinical
      experience with highly selective inhibitors of COX 2, indeed, suggests that these
      compounds are anti-inflammatory, but have an ulcer sparing effect. Clinical data
      with meloxicam also suggest that this theoretical effect is also translated into
      patient benefit. The selective inhibition of COX 2 is a very attractive new
      concept that has revitalised NSAID research and promises future hope for the
      treatment of inflammatory disease without gastric side effects.

PMID- 9032579
TI  - New NSAIDs and gastroduodenal damage.
AB  - Two isoforms of cyclooxygenase (COX) are described: COX-1 is a constitutive
      enzyme and is widely expressed in most tissues, COX-2 is an inducible enzyme and
      is abundant throughout the gastrointestinal tract. Expression of COX-2 can be
      induced locally by inflammatory stimuli and appears coincident with local
      prostaglandin (PG) production. Currently available non-steroidal antiinflammatory
      drugs (NSAIDs) are widely used for the treatment of inflammatory diseases;
      however, significant side-effects due to inhibition of COX-1 limit their use.
      Inhibitors of COX-2 are as active as non-selective NSAIDs and inhibit PG
      synthesis in inflammatory cells. In contrast to other NSAIDs, selective COX-2
      inhibitors do not cause ulcers in the stomach or intestine.

PMID- 9032581
TI  - Prevention of NSAID-gastropathy.
AB  - The role is reviewed of gastric antisecretory and mucosal protective drugs in the
      prevention of NSAID-induced gastric and duodenal mucosal lesions. The results of
      the randomized, double-blind, controlled trials show that misoprostol is the only
      antiulcer drug proven to be effective in the prevention of NSAID-induced gastric
      and duodenal ulcers as well as for reducing serious upper gastrointestinal
      complications (perforation and/or haemorrhage). However, recent data suggest that
      even omeprazole and high dose of H2-receptor antagonists may have a role in the
      prevention of NSAID-induced gastric and duodenal ulcerations.

PMID- 9032580
TI  - Gastroduodenal tolerability of highly specific cyclo-oxygenase-2 inhibitor.
AB  - Inhibition of constitutively expressed cyclo-oxygenase (COX-1) by NSAIDs is
      thought to play an important role is the gastrointestinal toxicity of NSAIDs. To
      minimise the intestinal toxicity of NSAIDS, highly selective COX-2 (induced at
      inflammatory sites) inhibitors have been developed. One such is flosulide. We
      assessed the gastroduodenal tolerability of flosulide (20 mg twice a day) in man
      and compared it with that of naproxen (500 mg twice a day) in a randomised,
      double blind crossover fashion in 19 patients with osteoarthrosis. Treatment
      period was 2 weeks with a 2-week washout period with endoscopy before and after
      each treatment. Gastroduodenal damage was assessed as by Lanza (Grades 0-4) and
      by the Gastroscopic Rating Scale (Grades 0-9). Flosulide was significantly better
      tolerated (p < 0.005, analyses of deviance) than naproxen. No stomach damage was
      seen in 13 (68%) patients following flosulide and 5 (37%) following naproxen (p <
      0.001). Lanza scores following flosulide (0.58) were significantly better than
      that of naproxen (1.47) (p < 0.001). The duodenal damage was mild with both
      treatments. The selective COX-2 inhibitor, flosulide, is significantly better
      tolerated and causes less gastric mucosal damage than naproxen when given for two
      weeks.

PMID- 9032582
TI  - Therapy of NSAIDs-induced gastropathy.
AB  - NSAID-induced gastropathy is the most frequent side effect due to NSAID use. The
      resulting clinical event is usually of little significance and only in a small
      percentage of cases results in serious side effects. Nevertheless, the large
      worldwide use of NSAIDs makes, even a rare side effect, numerically consistent.
      The pathogenesis of NSAID-induced gastropathy is related to two main mechanisms:
      an initial topical effect which is pH dependent and a systemic effect which is,
      more slowly developing, and mainly correlated to the inhibition of prostaglandin
      synthesis. The therapy of NSAID-gastropathy is almost completely identified with
      the therapy of NSAID ulceration because of its frequent relation to the
      development of potentially serious complications. In the case of symptomatic
      ulcer development the first therapeutic step is NSAID suspension and, in such a
      case all "antiulcer" drugs are efficient. When the NSAID can not be discontinued,
      omeprazole seems to be the most efficient drug; H2 blockers can promote ulcer
      healing but at a slower rate; sucralfate shows an efficacy similar to H2
      blockers; misoprostol is useful in the prevention of NSAID-gastropathy. However,
      it is not so efficient in the treatment of established lesions and shows poor
      efficacy in the reduction of dyspeptic symptoms. For each one of these drugs it
      is necessary to obtain further data.

PMID- 9032583
TI  - Exocrine pancreatic secretion and plasma levels of cholecystokinin, pancreatic
      polypeptide, and somatostatin after single and combined intraduodenal application
      of different bile salts in man.
AB  - Bile salts are intraduodenal stimulants of basal pancreatic secretion. This study
      aims to show whether the three main bile salts of human bile differ in their
      action on pancreatic secretion, and whether they enhance or inhibit each other
      after combined use. Furthermore, the effect on gastroenteropancreatic peptide
      release is evaluated. Twelve subjects were provided with a gastroduodenal double
      lumen tube. Equimolar doses (0.6 mmol) of taurocholate (322 mg),
      taurodeoxycholate (313 mg), and a combination of both stimuli were given
      intraduodenally. Another 12 subjects received taurochenodeoxycholate (313 mg)
      instead of taurocholate. Volume, bicarbonate, trypsin, and lipase were determined
      in duodenal aspirates. Cholecystokinin, pancreatic polypeptide, and somatostatin
      were measured radioimmunologically in plasma samples. All bile salts and
      combinations exerted a significant hydrokinetic and ecbolic effect. The
      hydrokinetic response of the combined stimuli was significantly higher as
      compared with taurocholate and taurochenodeoxycholate, respectively. As far as
      concerns the ecbolic response, the difference was significant only for trypsin
      output as compared with taurochenodeoxycholate. Plasma cholecystokinin rose
      significantly only after the combined stimuli. Pancreatic polypeptide and
      somatostatin increased significantly after all stimuli, except pancreatic
      polypeptide after taurocholate. Combined use enhances the hydrokinetic and
      ecbolic effects of single bile salts. Cholecystokinin may, hereby, be involved as
      a mediator of the ecbolic effect. Pancreatic polypeptide release indicates
      cholinergic mechanisms as further mediators. As demonstrated by somatostatin
      release, counter-regulatory mechanisms are also triggered by intraduodenal bile
      salts.

PMID- 9032584
TI  - Helicobacter pylori gastritis and non-ulcer dyspepsia in childhood. Efficacy of
      one-week triple antimicrobial therapy in eradicating the organism.
AB  - Efficacy of one-week triple antimicrobial therapy (bismuth, tinidazole,
      amoxicillin) as compared to the same drug combination given for 4 weeks was
      assessed in children with Helicobacter pylori (H. pylori) gastritis and non-ulcer
      dyspepsia. Twenty-six patients (group A) and 30 (group B) had one-week and four
      week schedule, respectively. Eradication (absence of organism at endoscopy at
      least 1 month after ending treatment) was achieved in 84.6% of group A (22) and
      83.3% of group B (25), with marked reduction of histological gastritis score in
      both groups. Among patients with eradicated H. pylori, symptoms improved
      significantly in 14 and 16 patients of group A and B, respectively, but were
      still present in 17 (8 group A, 9 group B). The latter showed gastroparesis and
      abnormal gastro-oesophageal reflux at a subsequent diagnostic work-up and
      improved with prokinetic therapy. In 3 patients of group A and 3 of group B,
      symptoms improved despite persistence of bacterium into the stomach. Finally, in
      3 cases (1 group A, 2 group B) both symptoms and H. pylori infection were
      unchanged. At 6 month follow-up, symptoms were present in 7 patients (3 group A,
      4 group B): 6 of them (3 group A, 3 group B) showed H. pylori gastritis at
      endoscopy. We conclude that in children with dyspepsia and H. pylori gastritis
      one-week triple antimicrobial schedule is effective in eradicating bacterium;
      however, detection of H. pylori gastritis in dyspeptic children does not
      invariably indicate a pathogenic role of the organism in these patients.

PMID- 9032585
TI  - Serum cholesterol and chronic hepatitis C.
AB  - Total serum cholesterol levels have been studied in 100 patients with
      histological diagnoses of chronic hepatitis B and 100 wit chronic Hepatitis C,
      all without cirrhosis, and two age- and sex-matched control groups (B and C).
      Mean serum cholesterol levels of the groups were compared also in relation to
      sex, liver function, duration of the disease, alcohol intake, mass index, liver
      enzymes, presence of liver steatosis and severity of the liver disease on the
      basis of the histological activity index. The percentages of patients with serum
      cholesterol level < 150 mg/dl and > 240 mg/dl were also calculated. The mean
      serum cholesterol level was significantly lower in hepatitis C: 176 md/dl vs 194
      mg/dl of hepatitis B (p = 0.004) and 198 of control C (p = 0.000). Twenty eight
      hepatitis C patients had serum cholesterol < 150 mg/dl vs 10 with hepatitis B (p
      = 0.001). In multivariate regression analysis, only the type of virus infection
      was independent related to serum cholesterol level (p = 0.0063).

PMID- 9032586
TI  - Effect of fedotozine on human distal colon.
AB  - Fedotozine was rested in colonic strips removed during surgery from patients
      suffering from different diseases of the colon; the effects were compared to
      those of morphine and of the selective opiate agonist U-69593. Fedotozine did not
      affect the spontaneous motility of human colonic strips, unless very high
      concentrations were used. Fedotozine (10(-6)-3 x 10(-4) M) induced a
      concentration-dependent reduction of the excitatory effect induced by field
      stimulation, an effect which was partially mimicked by compound U-69593 and by
      morphine but not inhibited by naloxone. The cumulative dose-response curve to
      exogenous acetylcholine was inhibited by fedotozine (3 x 10(-4) M), whereas
      morphine had no effect up to 3 x 10(-4) M. In colonic strips incubated with [3H]
      choline, fedotozine (10(-5)-10(-4) M) induced an erratic decrease of
      acetylcholine-release induced by electric stimulation. In our experimental model,
      the inhibitory effect of fedotozine does not seem to be related to opioid
      receptor activation.

PMID- 9032587
TI  - Evidence against colonic mucosa colonisation by Helicobacter pylori. Lack of a
      specific antibody response in homogenates of rectal endoscopic biopsies.
AB  - Aim of this study is to provide indirect evidence that human colonic mucosa
      harbour Helicobacter pylori. The antibody response of IgG and IgA class against
      Helicobacter pylori was examined in autologous homogenate of gastric and rectal
      endoscopic biopsies from 26 patients and in rectal samples of a further 36. All
      had a documented (histology and/or serology) Helicobacter pylori status.
      Helicobacter pylori specific IgG and IgA were measured by an in-house ELISA. In
      Helicobacter pylori positive patients having both gastric and rectal homogenate,
      mean level of Helicobacter pylori IgG and IgA was higher in gastric than in
      rectal samples (0.810 +/- 0.668 optical density vs 0.329 +/- 0.509 optical
      density for IgG, p = 0.007 and 0.660 +/- 0.477 vs 0.116 +/- 0.229 for IgA, p <
      0.001, respectively). In each patient, level of the two isotypes was clearly
      higher in gastric than in autologous rectal sample. In the overall study
      population, mean level of Helicobacter pylori IgG in rectal homogenate was not
      significantly (p = 0.16) different between Helicobacter pylori positive (48/62,
      77%, 0.243 +/- 0.388 optical density) and negative (14/62, 23%; 0.095 +/- 0.088)
      patients. In same material, levels of Helicobacter pylori IgA were very low and
      undetectable either in Helicobacter pylori positive or negative patients.
      Although Helicobacter pylori IgG are detectable in rectal homogenates of
      Helicobacter pylori positive patients, present data suggest that these antibodies
      may not be local in origin but rather reflect circulating response. These
      observations do not support the view that large bowel mucosa is colonised by
      Helicobacter pylori.

PMID- 9032588
TI  - High prevalence of hepatitis C virus (HCV) genotype 2 in Italian patients with
      chronic liver disease.
AB  - The prevalence of different genotypes of Hepatitis C virus may vary between
      geographic areas and it is possible that various genotypes have different
      pathogenic characteristics. Therefore, 90 consecutive Italian patients anti
      Hepatitis C Virus positive with a broad spectrum of chronic liver disease, have
      been analysed to observe prevalence of various genotypes of Hepatitis C Virus.
      Genotyping was performed by polymerase chain reaction with a set of nested
      biotinylated primers, located in 5'UTR region. Genotype 1b and genotype 2a were
      the most commonly encountered (respectively, 50% and 37%) whereas other genotypes
      were rare. The unexpected high prevalence of genotype 2a allowed direct
      comparison of clinical characteristics and response to therapy between patients
      with genotype 2a and those with 1b. Genotype 1b was more prevalent than 2a in
      patients over 60 years (29 vs 12) and in those with more severe liver disease (34
      vs 16). In a univariate analysis, genotype 2a was associated with less severe
      liver disease (p = 0.02) and younger age (p = 0.018), in comparison with genotype
      1b. Patients with genotype 2a responded to interferon alpha therapy better than
      those with 1b (p = 0.007). In a multivariate analysis, only younger age was
      associated with genotype 2a. Genotype 2a (in comparison with 1b) and absence of
      cirrhosis were independent predictors of response to interferon alpha. In
      conclusion, genotype 2a is playing an emerging role in younger Italian patients
      and seems more sensitive than 1b to interferon alpha therapy.

PMID- 9032589
TI  - Serum pepsinogen I levels and acid secretion in Helicobacter pylori associated
      enlarged fold gastritis.
AB  - It has been shown that serum pepsinogen I levels are correlated with maximal acid
      outputs and can be used as an indicator for parietal cell mass. In this study,
      the effect of Helicobacter pylori infection on the relationship between serum
      pepsinogen I levels and maximal acid outputs was investigated in 27 patients with
      Helicobacter pylori associated enlarged fold gastritis. Before treatment, serum
      pepsinogen I levels and maximal acid outputs were not significantly correlated.
      After eradication of Helicobacter pylori, a significant positive correlation was
      found between serum pepsinogen I levels and maximal acid outputs with a
      significant increase in pepsinogen I levels and a significant increase in maximal
      acid outputs. These results indicate that Helicobacter pylori infection distorts
      the relationship between serum pepsinogen I levels and maximal acid outputs by
      elevating the former and lowering the latter, and that serum pepsinogen I level
      after eradication of Helicobacter pylori may reflect parietal cell mass in
      patients with Helicobacter pylori associated enlarged fold gastritis.

PMID- 9032590
TI  - Primary gastro-oesophageal reflux disease and irritable oesophagus syndrome as
      causes of recurrent abdominal pain in children.
AB  - Cases of two adolescents with recurrent abdominal pain, localized in the
      periumbilical area, due to primary oesophageal disorders are reported. Food
      allergy or intolerance, as well as other paediatric causes, were not involved in
      the pathogenesis of recurrent abdominal pain in these two patients. Case 1 was
      affected by primary gastro-oesophageal reflux disease: upper endoscopy with
      biopsies and oesophageal 24-hour pH-monitoring showed mild oesophagitis and
      pathological reflux index, respectively. Case 2 was affected by "irritable
      oesophagus syndrome": upper endoscopy with biopsies was normal and oesophageal 24
      hour pH-monitoring showed a close correlation between gastro-oesophageal reflux
      and recurrent abdominal pain episodes. Both patients were successfully treated
      with cisapride (0.2 mg/kg t.i.d.) and ranitidine (2.5 mg/KG b.i.d.). These
      reports suggest that primary gastro-oesophageal reflux disease and irritable
      oesophagus syndrome may cause recurrent abdominal pain in children.

PMID- 9032591
TI  - Hepatitis G virus in liver disease: cause or case?

PMID- 9032592
TI  - [Comparison between monotherapy with imipenem/cilastatin sodium (IPM/CS) and
      combinations of IPM/CS and other drugs for treating bacterial infections in
      patients with hematopoietic disorders].
AB  - One hundred and nine patients with infections concurrent with hematopoietic
      disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone
      (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS
      combination therapy). The following results were obtained. 1. One hundred and
      nine patients were allocated at random to two groups: 53 patients to IPM/CS
      monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6
      and 8 in the 2 groups, respectively) were excluded from the clinical evaluation.
      There were not significant differences between the two groups with respect to the
      background. 2. The efficacy rates of the 2 treatments against bacterial
      infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients
      with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0%
      in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS
      combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with
      FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients. The
      differences between the two groups were not significant. 3. Among the drugs used
      in combination with IPM/CS, antibiotics other than penicillins, cephalosporins,
      and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7%
      was obtained. 4. Bacteriologically, 19 and 17 strains were isolated from the
      IPM/CS monotherapy and combination therapy groups respectively, and the
      eradication rates were 100% and 88.9% respectively. 5. Side effects were noted in
      2 patients in the IPM/CS monotherapy group and 7 in the combination therapy
      group, but all of these resolved after discontinuation or completion of the
      treatment. The efficacies against severe bacterial infections in the presence of
      hematopoietic disorders were not different between IPM/CS alone and IPM/CS in
      combination with other antibiotics. Adverse reactions were uncommon with the
      monotherapy.

PMID- 9032594
TI  - [Antimicrobial activities of cefetamet against clinical isolates from urinary
      tract infection].
AB  - In order to evaluate antimicrobial activity of cefetamet (CEMT), minimum
      inhibitory concentrations (MICs) of CEMT and control drugs were determined
      against Gram-negative rods mainly from complicated urinary tract infections
      examined in our laboratory from April to September of 1994. The results are
      summarized as follows; 1. The obtained strains were Citrobacter diversus 20,
      Citrobacter freundii 30, Enterobacter aerogenes 20, Enterobacter cloacae 30,
      Serratia marcescens 30, Proteus mirabilis 30, Proteus vulgaris 20 and Morganella
      morganii 30 strains, a total of 210 strains. 2. Excluding some resistant strains,
      the MIC-distribution showed showed that CEMT had strong antimicrobial activities
      against those strains from the MIC-distribution of this investigation. Compared
      to reports on CEMT in 1989, the MIC80 of CEMT in this investigation against
      clinical isolates were similar. The MIC50's of CEMT against E. aerogenes, S.
      marcescens, P. mirabilis, P. vulgaris and M. morganii in the previous examination
      were equal to or similar to the current results, but the MIC50's against C.
      freundii and E. cloacae were lower than the value of this report. The detection
      frequency of highly resistant strains of C. freundii and E. cloacae to cefteram
      and cefixime were similar to that of CEMT-resistant strains. Multiple drug
      resistant strains, among these bacterial species seemed to be increasing. 3.
      Compared to oral antibacterial agents of oxime cephems that were used in the
      past, CEMT showed higher peak values of urinary excretion concentration and
      higher blood levels were sustained for a longer period of time. CEMT-PI will be
      effective against urinary tract infections.

PMID- 9032593
TI  - [Clinical study on a concomitant therapy with fluconazole and human recombinant
      granulocyte colony stimulating factor in the treatment of systemic fungal
      infections with hematological disorders].
AB  - The clinical efficacy and the safety of concomitant therapy with fluconazole and
      recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared
      with fluconazole monotherapy in neutropenic patients with hematological
      disorders. The clinical efficacy rate was 73.5% (25/34) in the combination
      therapy and 48.1% (37/77) in monotherapy. The difference between the two is
      statistically significant. Side effects were not observed in the combination
      group, but laboratory abnormalities were found in 6 patients with an incident
      rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected
      as empiric therapy for systemic fungal infection associated with hematological
      disorders, since this combination therapy showed high efficacy and low incident
      of side effects. Some patients, however, did not show increased neutrophil counts
      in spite of rhG-CSF administration.

PMID- 9032595
TI  - [Preclinical and clinical studies on the efficacy of bifonazole in patients with
      tinea pedis at 10 years after approval. Part 1. Susceptibility to bifonazole of
      clinical isolates of dermatophytes].
AB  - An investigation was carried out to determine whether or not here had been any
      changes in the susceptibility of clinically isolated strains of Trichophyton
      metagrophytes and Trichophyton rubrum (both leading causes of tinea) to
      bifonazole, an imidazole derivative and antifungal for topical use.
      Susceptibility was measured in 107 strains of these fungi isolated from clinical
      samples during a study on the treatment of tinea pedis with Mycospor cream in
      1995, 42 strains isolated and stored in 1990, and 39 strains isolated and stored
      prior to development of the drug. The results are as follows: (1) There was no
      distinct difference in the susceptibility to bifonazole of T. mentagrophytes
      strains isolated before 1986 and those isolated in 1990 or 1995. (2) T. rubrum
      strains isolated before 1986 were slightly more susceptible to bifonazole than
      those isolated in 1995, while the 1990 strains were slightly less susceptible
      than the 1995 strains, but the difference was not significant. (3) The highest
      MICs of bifonazole for all the T. mentagrophytes and T. rubrum strains isolated
      from before 1986 and those in 1995 were relatively low, being 2.5 micrograms/ml
      and 1.25 micrograms/ml, respectively. These results suggest that no resistance or
      reduced susceptibility to bifonazole has emerged among clinical isolates of
      dermatophytes since the development of the drug.

PMID- 9032596
TI  - [Fundamental and clinical studies on the efficacy of bifonazole in patients with
      tinea pedis at 10 years after approval. Part 2. Clinical evaluation].
AB  - The usefulness of bifonazole (Mycospor), a topical imidazole antifungal agent
      approved 10 years ago, was evaluated for the treatment of tinea pedis. Mycospor
      cream was applied by 141 patients with tinea pedis once daily for 4 233ks, and
      the clinical efficacy and adverse reactions (as well as any correlations with
      susceptibility of isolates and the mycological activity of the agent against
      these isolates) were studied. The results were then compared to those of a
      previous study. The following results were obtained. 1. Mycological activity
      Mycological examination results became negative in 63.2% (36/57) of the patients
      with plantar tinea pedis, in 94.1% (32/34) of those with interdigital tinea
      pedis, and in 74.7% (68/91) of all tinea pedis patients. 2. Mycological activity
      and MIC No correlation was found between the MICs of bifonazole against the
      pathogenic fungi and the rate of eradication on mycological examination. 3.
      Improvement of symptoms The improvement rates for local symptoms were 82.5% for
      plantar tinea pedis, 85.7% for interdigital tinea pedis, and 83.7% for all tinea
      pedis. 4. Clinical efficacy Good clinical efficacies were found in 61.4% of the
      patients with plantar tinea pedis, in 88.6% of those with interdigital tinea
      pedis, and in 71.7% of all patients. 5. Safety Regarding adverse reactions, what
      seemed to be contact dermatitis was reported in 5 out of 127 cases (3.9%). The
      reaction decreased or disappeared in all cases. 6. Usefulness Mycospor was found
      to be useful in 64.9% of patients with plantar tinea pedis, in 88.6% of those
      with interdigital tinea pedis, and in 73.9% of all tinea pedis patients. 7.
      Comparison with former results The results obtained in the present clinical study
      were comparable to those obtained in patients with tinea pedis treated in a
      double-blind comparative study conducted during the development of as a new
      topical antifungal agent. From the above results, Mycospor cream was confirmed to
      be still useful, although it has been used widely for the topical treatment of
      cutaneous mycoses in the past 10 years since its approval.

PMID- 9032597
TI  - [Growth inhibitory effects of ubenimex on leukemic cell lines resistant to
      chemotherapeutic agents].
AB  - Ubenimex (Bestatin, Ubx) has been shown to have anti-tumor activity and immuno
      modulating activities. Ubx has been used in immuno-therapy in combination with
      remission maintenance chemotherapy after induction of complete remission for
      adult acute non-lymphocytic leukemia (ANLL, AML). Daunomycin (DNR),
      arabinosylcytosine (Ara-C) and 6-mercaptopurine (6-MP) are used for the standard
      chemotherapy for ANLL. It is, however, believed that emergence of resistant cells
      to chemotherapy cause minimal residual leukemia resulting in poor prognosis. Ubx
      has been administered in combination with these chemotherapeutic agents. We
      examined the combinatorial effect of Ubx with DNR, Ara-C, 6-MP and etoposide on
      K562 leukemic cell line and the chemotherapeutic agent resistant cells derived
      from K562 cell line. Ubx showed growth inhibitory effects on these cell lines. A
      synergistic effect was observed on growth inhibition and with colony formation of
      parent k562 cell line when DNR and Ubx were used in combination. A combination of
      Ubx with Ara-C or etoposide showed additional effects on parent cells and other
      resistant cell lines. The combined growth inhibitory effect of 6-MP and Ubx was
      stronger than the effect of 6-MP alone. These results show that Ubx has a direct
      growth inhibitory effect on leukemic cells and additional or synergistic effects
      are obtained on K562 leukemic cell line and on chemotherapeutic agent resistant
      cells derived from the K562 cell line when Ubx is used combination with the above
      chemotherapeutic agents.

PMID- 9032598
TI  - The use of micro-titanium mesh for maxillary sinus wall reconstruction.
AB  - Operations on the maxillary sinus can lead to extensive bony defects of the
      facial and laterodorsal walls of the sinus. If there is no autogenous bone
      material available, the problem is to find a suitable substitute for
      reconstruction. We examined the suitability of micro-titanium mesh for
      reconstruction of the walls of the maxillary sinus. In 13 adult patients large
      defects of the walls of the maxillary sinus were reconstructed using micro
      titanium mesh. Indications for operation were tumours, large dental-type cysts,
      traumatic bone loss and chronic inflammation in sinuses which had been previously
      operated on. Clinical and radiological examinations were carried out immediately
      after surgery and after a 3 months interval. Control by sinuscopy was performed
      in all patients. Great importance was attached to the following aspects: 1.
      correctly shaped reconstruction of the maxillary sinus 2. prevention of soft
      tissue prolapse into the sinus 3. aeration of the maxillary sinus 4. preservation
      of the facial contour

PMID- 9032599
TI  - Aesthetic and functional reconstruction with the trapezius osseomyocutaneous flap
      and dental implants in oral cavity cancer patients.
AB  - The trapezius osseomyocutaneous flap is the only pedicled flap that is able to
      transfer vascularized bone for mandibular reconstruction as well as skin for
      intra-extra oral reconstruction. The trapezius muscle also helps to fill the
      defect created by the neck dissection and covers the vessels of the neck. This
      flap has been used in our maxillofacial surgery service during the past 14 years.
      In spite of having incorporated microvascular flaps in our reconstructive
      techniques it continues to be one of the flaps we use in selected patients for
      bone and soft tissue compound defects of the oral cavity. We describe in this
      article our experience using this flap with dental implants in order to achieve a
      functional reconstruction. We also discuss when we use this flap for mandibular
      reconstruction and when a free vascularized flap is used.

PMID- 9032600
TI  - Experience with the osteocutaneous fibula flap: an analysis of 24 consecutive
      reconstructions of composite mandibular defects.
AB  - Based on findings from anatomical dissections of the skin of the peroneal artery,
      we used the osteocutaneous fibula flap for combined replacement of the mandible
      and floor of the mouth in 24 patients, form November 1993 to December 1995. There
      were 22 primary and 2 secondary reconstructions; the mean age of the patients (2
      women and 22 men) was 64 years. The length of the fibula segments ranged between
      5.5 and 18 cm, the size of the skin component between 3 x 5 and 6 x 15 cm.
      Corresponding to the results of our anatomical studies, the skin island was
      exclusively raised form the distal third of the lower leg, and the donor sites
      were generally covered with split thickness skin grafts. The average length of
      the dissected vascular pedicle was 11 cm, so that a vein graft was only required
      in one case. Flap raising and tumour resection were always carried out
      simultaneously. Fibula osteosynthesis was done with titanium miniplates; the
      insertion of endosseous implants followed secondarily. The success rate was 95.8%
      with one transplant loss and pseudarthrosis in one case. Despite the limited
      width of the fibula, the shape of the mandible was satisfactorily reconstructed
      in all patients, and the thin, pliable component enabled intraoral coverage with
      only negligible surplus volume. Chronic wound-healing disturbances at the donor
      site of the skin island occurred in two cases; impairment of walking ability was
      not detected. According to our experience, the use of the osteocutaneous fibula
      flap is a valuable method for the reconstruction of composite mandibular defects.

PMID- 9032601
TI  - Current status of retinoids in chemoprevention of oral squamous cell carcinoma:
      an overview.
AB  - Squamous cell carcinoma of the oral cavity and oropharynx may be amenable to
      chemoprevention. This review focuses on current concepts of mechanisms in oral
      carcinogenesis, as well as the evidence that retinoids have a role in the primary
      and secondary prevention of this malignancy.

PMID- 9032602
TI  - Structural changes and cell viability of cultured epithelium after freezing
      storage.
AB  - Numerous clinical reports have shown the utility of cultured epithelial grafting
      in the field of plastic and reconstruction surgery. Recently, freezing storage of
      the cultured epithelium has been tried and has successfully grafted after
      thawing. It is clinically convenient if it is possible for cultured epithelium to
      keep its normal structure and viability. However, few papers have described the
      structural changes in cultured epithelium after freezing storage. In the present
      study, the morphological changes and cell viability of cultured mucosal
      epithelial sheets after freezing were studied in comparison with cultured
      epidermal sheets. Furthermore, we discuss the effect of storage temperature and
      cryoprotectants. As a result, there were some structural changes such as vacuolar
      degeneration in the cultured mucosal sheets using dimethyl sulphoxide (DMSO) as a
      cryoprotectant. Such changes were more clearly observed at -80 degrees C than at 
      196 degrees C with DMSO. However, little morphological change was observed in
      both epithelial sheets cultured with glycerin. The cell viability analysed by
      flow cytometry showed that more than 62% of the cells kept their viability after
      freezing storage. These results suggest that the optimum conditions of freezing
      for cultured epithelium were -196 degrees C storage by slow cooling methods with
      glycerin as a cryoprotectant.

PMID- 9032603
TI  - Transplantation of cultured mucosal epithelium: an experimental study.
AB  - We investigated morphological changes after transplantation of cultured mucosal
      epithelium using a modified Barrandon's method (1988). Serially cultivated human
      mucosal epithelium was transplanted onto the reverse side of rectangular dorsal
      skin flaps in hairless mice. The morphological changes in the epithelium were
      studied using paraffin sections. The modified Barrandon's method used in this
      study has advantages such as minimum external trauma and less chance of
      infection. The cultured epithelium was taken within 1 week and gradually
      increased its epithelial thickness. Keratinized epithelium arises after 3 weeks.
      At 4 weeks after grafting, the grafted epithelium comprised 7-10 cell layers. The
      structure of transplanted tissue, in conjunction with surrounding connective
      tissues, showed dermis-like features at day 7 after transplantation. From these
      results, it was confirmed that cultured mucosal epithelium could be successfully
      transplanted and its morphology was similar to that of normal mucosal tissue.

PMID- 9032604
TI  - Self-regenerating bone implant: ectopic osteoinduction following intramuscular
      implantation of a combination of rhBMP-2, atelopeptide type I collagen and porous
      hydroxyapatite.
AB  - A combination of recombinant human bone morphogenetic protein-2 (rhBMP-2),
      atelopeptide Type I collagen (CL) as a carrier and porous hydroxyapatite (pHAP)
      was implanted in a calf muscle pouch of the rat. Three rhBMP-2-implanted groups
      (2, 10 and 50 micrograms; each n = 5) and the control group (n = 5), in which
      only CL and pHAP were implanted, were established. Three weeks later, the
      implants were examined.

PMID- 9032605
TI  - Management of necrotizing fasciitis in the neck.
AB  - Necrotizing fasciitis is a soft tissue infection, usually polymicrobial,
      characterized by necrosis of fascia and subcutaneous tissue. Although it more
      commonly involves the groin, abdomen, and extremities, it may also occur in the
      head and neck. We report a case of cervical necrotizing fasciitis arising from a
      dental infection and review the cause, pathophysiology, diagnosis and treatment
      of this potentially lethal entity. Early detection and accurate intervention are
      emphasized. Extensive surgical debridement completed with hyperbaric oxygen
      therapy and antibiotics are the mainstay of treatment.

PMID- 9032606
TI  - Three cases of oblique facial cleft.
AB  - Three patients with an oblique facial cleft are described. One patient displayed
      ring constriction, lymphoedema, distal pseudosyndactyly and an occipital
      encephalocele to which an amniotic band was attached at birth. Therefore, it was
      obvious that the oblique facial cleft was accompanied by an amnion rupture
      sequence. These signs were not apparent in the other patients. However, one of
      the patients demonstrated various anomalies, amongst which syndactyly on the
      right foot, scoliosis, microcephaly, microphthalmia and corneal opacity suggested
      that the patient may have been affected by the amnion rupture sequence, except
      for polydactyly on the left foot, cleft hand and vertebra plana.

PMID- 9032607
TI  - Epidemiology of orofacial clefts in Slovenia, 1973-1993: comparison of the
      incidence in six European countries.
AB  - For over 40 years, all children with orofacial clefts in Slovenia have been
      treated at the Department of Maxillofacial Surgery in Ljubljana, which maintains
      a register of these anomalies. Since 1987, clefts have also been registered
      within the framework of the perinatal Information System. An analysis of patients
      included in each of the two sources showed that an estimated 3.5% of cases were
      missing from the Cleft Register of the Department of Maxillofacial Surgery and
      15% from the Perinatal Registry. The incidence of clefts in the period 1973-1993
      was 1.64 per 1000 live births, with an increasing trend of 0.02 per year.
      Considerable differences were established among different geographic regions of
      Slovenia. Comparison with the data for Finland, Denmark, Hungary, Poland and
      Bohemia revealed some synchronicity of fluctuations in the incidence of clefting
      in these countries. The last two observations suggest that exogenous factors of
      two types play a part in the aetiology of orofacial clefts: some are limited in
      their action to a small geographical area, while others exert their influence
      simultaneously in areas several thousand kilometers apart.

PMID- 9032619
TI  - Medicinal plants used in the Barros Area, Badajoz Province, Spain.
AB  - A study of the wild and cultivated medicinal plants used in the Barros Area
      (southern Spain) is reported, 48 plants distributed among 20 different families
      are used in the treatment of various human diseases. The use of Bellis annua L.
      Centaurea ornata Wild., Leuzea conifera (L.) DC., Pulicaria paludosa Link and
      Asparagus aphyllus L. is reported.

PMID- 9032620
TI  - Evaluation of Nigerian traditional medicine: effects of Gakani, a herbal anti
      asthmatic drug.
AB  - The anti-asthmatic potential of Gakani, a popular herbal drug in Nigeria was
      investigated. The LD50 values of the freeze-dried aqueous extract in mice and
      rats were 20.9 +/- 2.4 mg/kg and 18.6 +/- 4 mg/kg, respectively. The extract
      unsurmountably blocked the effects of histamine and isoprenaline on the guinea
      pig tracheaL chain. It produced initial dose-related contractions of the isolated
      guinea pig ileum and rat stomach strip, which was followed by persistent
      autoinhibition and inhibition of histamine- and 5-hydroxytryptamine (5-HT)
      induced responses of the two preparations, respectively. The extract had good
      anti-inflammatory effect in rats, causing a dose-related inhibition of the
      increase in the paw circumference (acute inflammation) induced by subplantar
      injection of fresh egg albumin. These results highlight the anti-asthmatic and
      toxic potential of this preparation and the need for a systemic approach in the
      study of traditional medicines.

PMID- 9032621
TI  - Anti-inflammatory and antiulcer activity of Teucrium buxifolium.
AB  - Teucrium buxifolium Spanish endemic, have traditionally been used for the
      treatment of rheumatic and other inflammatory affections. In this work,
      phytochemical screening was carried out to ascertain the qualitative composition
      of this species and we have studied the anti-inflammatory and antiulcer activity
      of Teucrium buxifolium. This species has exhibited potent anti-inflammatory
      properties against experimentally-induced arthritis and carrageenin paw edema.
      Additionally, Teucrium buxifolium species have displayed significant antiulcer
      and cytoprotective activity.

PMID- 9032622
TI  - Immunomodulatory activities of Cedrela lilloi and Trichilia elegans aqueous leaf
      extracts.
AB  - The effects of Cedrela lilloi and Trichilia elegans (Meliaceae) aqueous leaf
      extracts on several parameters of the mouse immune system were studied. Both
      extracts showed a strong anticomplementary activity and inhibited the
      phagocytosis of opsonized sheep erythrocytes and the activation of the oxidative
      metabolism by opsonized zymosan on peritoneal macrophages. The in vitro
      proliferation of spleen T-lymphocytes was also impaired. Furthermore, treatment
      of mice with the extracts diminished the delayed-type hypersensitivity response
      to sheep erythrocytes. These results suggest that both extracts exert a marked
      immunomodulatory effect on the mouse immune system.

PMID- 9032623
TI  - Involvement of calcium in the cardiac depressant actions of a garlic dialysate.
AB  - In order to elucidate a possible role for calcium on the negative cardiotropic
      effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we
      studied: (a) the effects of our extract 15 min after preincubation with high and
      low concentrations of extracellular calcium ([Ca2+]o) on left and right activity
      of rat atria. The negative inotropism of garlic dialysate increased with calcium
      0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant
      reduction of this depressant effect. None of these treatments modified the
      negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil
      (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration
      dependent synergism of the log concentration-effect of garlic dialysate on left
      atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the
      inhibitory chronotropism of garlic in right atria; (c) negative inotropic and
      chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M)
      were antagonized as expected by preincubation with Bay K-8644. Depressant actions
      of garlic were not modified with this pretreatment. These results suggest that
      the negative inotropic effect of our garlic dialysate is related to [Ca2+]o
      availability. It is possible that a restriction of intracellular calcium
      contributes to this effect. However, the negative chronotropic effect of garlic
      is scarcely affected by these modifications.

PMID- 9032624
TI  - Medicinal plants of the eastern region of Madagascar.
AB  - Sixty-eight plants used in the traditional medicinal practices of the
      Betsimisaraka and Tanala peoples of the eastern region of Madagascar are
      reported. Preparations and utilizations of these medicinal plants are as varied
      as the plants themselves. Some of the plants discussed are known to science, but
      because of the diversity of tribal groups in Madagascar, new preparations and
      utilizations of these plants were based on the ethnobotanical data collected from
      the Betsimisaraka and Tanala. Many of the plants discussed remain to be
      chemically tested. Ethnopharmacological information is in danger of being lost in
      Madagascar as slash and burn agriculture destroys much of the forest, and the
      elder traditional healers, often illiterate, pass away without handing down their
      knowledge.

PMID- 9032625
TI  - Anti-allergic effect of an aqueous extract of wu-hu-tang.
AB  - Wu-Hu-Tang (WHT), a Chinese formulation which consists of seven crude drugs, has
      been used for the treatment of asthma for hundreds of years. In this paper, an
      investigation on the anti-allergic activity of an aqueous extract of WHT was
      undertaken to find the pharmacological basis for the ethnomedical use of the
      formulation. WHT produced a significant inhibition on the homologous passive
      cutaneous anaphylaxis (PCA) in rats and the heterologous PCA in mice, decreased
      the degranulation of mast cells of calvarial periosteum in rats, inhibited the
      release of anaphylactic mediators from sensitized lung tissues of guinea pigs and
      the contraction of isolated guinea pigs ileum induced by histamine. These results
      indicated that the therapeutic activity of WHT for asthma may be related to its
      inhibitory effects on immediate hypersensitivity.

PMID- 9032626
TI  - Immunomodulatory effects of NIM-76, a volatile fraction from Neem oil.
AB  - The immunomodulatory properties of NIM-76 have been described in this paper. Pre
      treatment of rats with a single i.p. injection of NIM-76 resulted in an increase
      in polymorphonuclear (PMN) leukocytes with a concomitant decrease in lymphocyte
      counts. The immunomodulatory activity of NIM-76 was found to be concentration
      dependent. At 120 mg/kg body weight, there was an enhanced macrophage activity
      and lymphocyte proliferation response, while the humoral component of immunity
      was unaffected. At higher concentrations of NIM-76 (300 mg/kg body weight), there
      was a stimulation of mitogen-induced lymphocyte proliferation, while macrophage
      activity remained unaffected. However, a fall in primary and secondary antibody
      titres was observed. The study indicates that NIM-76 acts through cell-mediated
      mechanisms by activating macrophages and lymphocytes.

PMID- 9032628
TI  - Anticandidal activity of Santolina chamaecyparissus volatile oil.
AB  - A search for naturally occurring drugs with antifungal activity lead to Santolina
      oil, a volatile oil distillate of Santolina chamaecyparissus. The studies
      revealed that Santolina oil was effective in controlling experimental candidiasis
      in vitro and in vivo. It had a synergistic effect on clotrimazole in controlling
      Candida albicans in vitro. It significantly controlled experimental vaginal
      candidiasis and experimental systemic candidosis. Santolina oil was able to
      control the superficial cutaneous mycoses. It is recommended as a potential
      candidate for further studies, including clinical studies.

PMID- 9032627
TI  - Gastric antiulcer and cytoprotective effect of Commiphora molmol in rats.
AB  - The aqueous suspension of Commiphora molmol (oleo-gum resin) has been screened
      for its potential to protect gastric mucosa against the ulcers caused by 80%
      ethanol, 25% NaCl, 0.2 M NaOH, indomethacin and combined indomethacin-ethanol
      treatment. C. molmol pretreatment at doses of 250, 500 and 1000 mg/kg provided
      dose-dependent protection against the ulcerogenic effects of different
      necrotizing agents used. The effects caused by ethanol were further investigated.
      Treatment of rats with 1 ml of 80% ethanol was found to cause depletion of
      stomach wall mucus, reduction in the concentration of protein, nucleic acids and
      NP-SH groups in the stomach wall. Ethanol treatment also caused histopathological
      lesions including necrosis, erosion, congestion and haemorrhage of the stomach
      wall. Pretreatment with C. molmol offered a dose-dependent protection against all
      these effects. In the same manner it affected the malondialdehyde concentration
      altered by ethanol treatment. C. molmol also offered protection against mucosal
      damage caused by indomethacin and its combination with ethanol. The protective
      effect of C. molmol observed in the present study is attributed to its effect on
      mucus production, increase in nucleic acid and non-protein sulfhydryl
      concentration, which appears to be mediated through its free radical-scavenging,
      thyroid-stimulating and prostaglandin-inducing properties.

PMID- 9032629
TI  - Hypolipidaemic activity of alpha-asarone in mice.

PMID- 9032630
TI  - Mupirocin resistance and methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Mupirocin has become the topical agent of choice for the elimination of
      methicillin-resistant Staphylococcus aureus (MRSA) carriage. The increased use of
      this antibiotic has been followed by reports of outbreaks due to MRSA with both
      low- and high-level resistance. Whilst low-level resistance is becoming more
      widespread, it is unlikely to have a major impact upon current practice. High
      level resistance is plasmid borne, and although uncommon, can lead to problems
      with elimination especially in an outbreak situation. Alternatives are available
      but uncertainty exists as to their efficacy and safety. Any strategy to limit the
      increase of mupirocin resistance in MRSA should emphasize the importance of
      controlled antibiotic use both for mupirocin and other agents.

PMID- 9032631
TI  - Risk factors for faecal carriage of Klebsiella pneumoniae producing extended
      spectrum beta-lactamase (ESBL-KP) in the intensive care unit.
AB  - In the course of an outbreak of extended-spectrum beta-lactamase-producing
      Klebsiella pneumoniae (ESBL-KP) in an intensive care unit (ICU), we conducted
      active surveillance to determine the risk factors for ESBL-KP faecal colonization
      of patients. We used weekly rectal samples during a four-month period. ESBL-KP
      was found in the faeces of 72 of 188 (38%) patients, and 42 (58%) of them were
      colonized within the first week of admission to the ICU. The probability of
      remaining free of faecal colonization was less than 20% at 30 days of ICU
      admission. The risk factors associated with ESBL-KP faecal colonization were
      clinical severity score at admission (P = 0.004), arterial catheterization (P =
      0.002), total parenteral nutrition (P = 0.04), urinary catheterization (P =
      0.01), mechanical ventilation (P < 0.001), and previous antibiotic therapy (P =
      0.04). A logistic regression analysis identified duration of urinary
      catheterization (OR:3.5; 95% CI 1.2-10.3) and mechanical ventilation (OR:4.6; 95%
      CI 1.1-19.3) as independent risk factors for ESBL-KP faecal colonization. Our
      results suggest that in an ESBL-KP prevalent environment, manipulations that
      facilitate cross-infection are the most relevant in the acquisition of the micro
      organism and risk increases throughout hospitalization.

PMID- 9032632
TI  - Prevention of infection in dental procedures.
AB  - The efficacy of a newly-developed anti-cross-contamination device in dentistry,
      the Air Flushing Clean System (AFCS), was tested under experimental and clinical
      conditions. In the experimental situation, a dental air turbine handpiece with or
      without AFCS was contaminated with two bacterial strains, Staphylococcus aureus
      FDA209P and Streptococcus mutants ATCC25175. After contamination with these
      bacteria, the handpieces were subjected to two disinfecting methods. Residual
      bacteria inside the handpiece or an air/water line were cultured and counted, and
      compared with controls. In this experiment, with AFCS but no dental vacuum
      suction, wiping of the handpiece with 70% ethanol gauze reduced the count of S.
      aureus by 99%. No bacterial contamination in the air/water line was detected
      after exchanging with an autoclaved handpiece. With AFCS and dental vacuum
      suction, bacterial contamination in the air/water line, as well as in the
      interior of the handpiece, was not detected. These results indicate that AFCS
      could reduce bacterial contamination within the air turbine handpiece more
      effectively than the conventional handpiece regardless of whether or not the
      dental vacuum suction was used.

PMID- 9032633
TI  - Methicillin-resistant Staphylococcus aureus in a cystic fibrosis unit.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infection in a cystic fibrosis
      (CF) unit was investigated. Two typing methods, phage-typing and restriction
      fragment length polymorphism (RFLP) by pulsed-field gel electrophoresis (PFGE)
      and phylogenetic analysis, showed that nonsocomial transmission of MRSA from the
      general hospital population had occurred. One instance of possible transmission
      between two patients was identified. However, transmission between two family
      members did not occur indicating a minimal risk of MRSA acquisition from social
      contact compared with hospital admission. This study supports policies for
      limiting CF-patient admission to hospital but transmission of MRSA does not
      appear to be a reason for limiting social contact with other CF patients.

PMID- 9032634
TI  - Prolongation of hospital stay and extra costs due to hospital-acquired infection
      in a neonatal unit.
AB  - A case-control study to evaluate the mean extra stay and corresponding cost of
      neonates acquiring a hospital-acquired infection (HAI) was performed on all
      patients admitted to a neonatology unit and discharged alive in 1994. Cases were
      identified from medical records. Controls were matched to cases for birthweight,
      gestational age, mode of admission to the unit, previous stay in an intensive
      care unit and presence of a central venous catheter. Costs were taken as those of
      the extra days attributable to HAI, i.e. the mean difference in the length of
      stay between cases and controls. Among a cohort of 616 neonates, 34 (5.5%) had
      one or more HAIs (average = 1.1). The mean extra cost per infected case was
      52,192 FF (US$10,440), corresponding to 5.2 extra days in hospital.

PMID- 9032635
TI  - Evaluation of the efficacy of a 3.2% glutaraldehyde product for disinfection of
      fibreoptic endoscopes with an automatic machine.
AB  - The efficacy of 'Cidex Plus' 3.2% alkaline glutaraldehyde was evaluated for the
      disinfection of fibreoptic endoscopes. The glutaraldehyde concentration in 'Cidex
      Plus', stored in an automatic machine (Olympus EW-20), remained higher than 2%
      (2.21%) even after a total of 102 disinfection cycles during 28 consecutive days.
      The results of the in-vitro study on antimicrobial activity showed that this
      alkaline glutaraldehyde product had a greater activity against 20 test organisms,
      including vegetative bacteria, bacterial spores, mycobacteria, and fungi, than 2%
      glutaraldehyde alone. The presence of 10 or 30% human serum did not appear to
      affect the activity of glutaraldehyde adversely. Instrument samples made from a
      variety of materials such as stainless steel, glass, teflon, etc. were not
      damaged after 168 h of immersion in alkaline glutaraldehyde, although it
      contained approximately 1.7 times more glutaraldehyde than 2% glutaraldehyde
      alone. Based on these results, 3.2% alkaline glutaraldehyde is considered to be a
      more effective disinfectant for fibreoptic endoscopes, with the use of an
      automatic machine, than 2% glutaraldehyde.

PMID- 9032636
TI  - Salt tolerance of EMRSA-16 and its effect on the sensitivity of screening
      cultures.
AB  - The salt (NaCl) tolerance of methicillin-resistant Staphylococcus aureus (EMRSA)
      16 was compared with 18 other MRSA isolates by an agar incorporation technique.
      The NaCl minimum inhibitory concentration (MIC) of EMRSA-16 was 7% which compared
      with an MIC50 of 7%, MIC90 of 10%, range (5.5-10.5%) for the other isolates.
      Study of the growth kinetics in broth containing NaCl at concentrations up to 10%
      indicated complete inhibition of growth by 7 and 10% NaCl and partial inhibition
      by 5%. Addition of EMRSA-16 at inocula of < or = 1 cfu/mL into salt broths
      revealed lower than expected EMRSA recovery from broths containing 5, 7.5 and 10%
      NaCl. Two and a half per cent NaCl broths were not inhibitory. Selective broth
      containing 2.5% NaCl should be considered for use when screening for EMRSA-16.

PMID- 9032637
TI  - Vancomycin-resistant gram-positive cocci: risk factors for faecal carriage.
AB  - This case-control study was undertaken to identify the risk factors for the
      gastrointestinal carriage of vancomycin-resistant, Gram-positive cocci (VRGPC)
      including vancomycin-resistant enterococci (VRE). Use of oral vancomycin (P =
      0.003) or cephalosporins (P = 0.03) and prolonged duration of stay in the
      hospital (P = 0.02) were found to be the significant risk factors. Other
      previously suggested risk factors such as location of the patients and presence
      of central venous or arterial lines were not significantly associated with
      carriage of VRGPC. Judicious usage of glycopeptides (particularly oral
      vancomycin) and cephalosporins is likely to be the most effective way to prevent
      and control the spread of VRGPC and VRE.

PMID- 9032638
TI  - Holy water, tap water, mineral water or water filters?

PMID- 9032639
TI  - Laboratory-acquired VTEC infection.

PMID- 9032640
TI  - Fragile X syndrome is less common than previously estimated.
AB  - In 1986, a population study of school children in the city of Coventry gave an
      overall prevalence in males and females for fragile X syndrome of 1/952. The 29
      children diagnosed as having fragile X syndrome in this study have been re
      evaluated with molecular diagnostic techniques. Eighteen of the original 29
      children have been found not to have the expansion of the FMR1 gene associated
      with fragile X syndrome. Revised prevalence figures have been calculated giving
      rise to an overall prevalence figure of 1/2720 (range 1/2198-1/3089). If the four
      children lost to follow up are also assumed not to have the fragile X syndrome,
      the revised prevalence figure was 1/5714 (range 1/4762-1/6349). Clinical review
      of boys with severe mental retardation from this and a subsidiary study show that
      the clinical features of head circumference greater than the 50th centile,
      testicular volume greater than the 50th centile, and IQ between 35 and 70 remain
      helpful in distinguishing boys with fragile X syndrome from those who have non
      specific mental retardation.

PMID- 9032641
TI  - Maternal uniparental disomy 7 in Silver-Russell syndrome.
AB  - Silver-Russell syndrome (SRS) is characterised by intrauterine and postnatal
      growth failure accompanied by a variable number of dysmorphic features. It is
      usually sporadic although a few familial cases have been described. In a
      prospective study of 33 patients with sporadic SRS, we have studied the parent of
      origin of chromosome 7 using variable number tandem repeat (VNTR) or
      microsatellite repeat markers and have identified two patients with maternal
      uniparental disomy of chromosome 7 (mUPD7). In one family, inconsistent
      inheritance of paternal alleles of markers on chromosomes other than 7 led to
      their exclusion from further study. The probands were clinically mild and
      symmetrical, but showed no gross clinical differences from the 30 patients with
      chromosome 7 derived from both parents.

PMID- 9032642
TI  - No evidence for uniparental disomy as a common cause of Sotos syndrome.
AB  - A number of rare diseases (including Sotos syndrome) of unknown aetiology, which
      occur mainly sporadically and with features of growth disorder and developmental
      delay, may be caused by imprinted genes and therefore be associated with UPD.
      Using 112 dinucleotide repeat DNA polymorphisms, we have examined parental
      inheritance of all autosome pairs, except chromosome 15, in 29 patients with
      Sotos syndrome. All informative cases showed biparental inheritance and no cases
      of UPD were found. We conclude that Sotos syndrome is either not caused by an
      imprinted gene or that UPD is rare or of a segmental form in its aetiology.

PMID- 9032643
TI  - Clinical, cytogenetic, and molecular analysis of three families with FRAXE.
AB  - The probe StB12.3 has been used to screen the FMR-1 gene in 42 pedigrees with a
      distal Xq fragile site for expansion of the CCG repeat and aberrant methylation
      of the FRAXA locus. Four families did not have a FRAXA mutation and were
      investigated further. Fluorescent in situ hybridisation (FISH) and molecular
      analyses showed that three of these families had an expansion at FRAXE and one at
      FRAXE. Detailed psychiatric, psychological, and behavioural features of three
      families with FRAXE identified in the study are presented. All the males who
      expressed FRAXE had a large methylated CCG repeat at FRAXF. All males with the
      mutation had some degree of mental handicap. This study illustrates the need for
      the FRAXE phenotype to be defined further.

PMID- 9032644
TI  - At least nine cases of trisomy 11q23-->qter in one generation as a result of
      familial t(11;13) translocation.
AB  - Carriers of balanced reciprocal translocations may have a (high) risk for
      producing liveborn children with an unbalanced karyotype. We report a large
      family in which a translocation between the long arm of chromosome 11 and the
      short arm of chromosome 13 is segregating in at least five generations. During
      the course of our study 15 carriers of the balanced translocation were identified
      and nine cases of partial trisomy of the long arm of chromosome 11 were detected
      during pre- and postnatal studies. Several of the patients were thoroughly
      clinically examined and compared with similar published cases.

PMID- 9032645
TI  - 46,XX, inv(6)(p21.1p23) in a pedigree with hereditary haemochromatosis.
AB  - Hereditary haemochromatosis (HFE) is a recessive genetic disease of iron overload
      which has been shown by linkage analysis to reside on the short arm of chromosome
      6, close to the major histocompatibility complex (MHC). Positional cloning of the
      putative HFE locus has been hampered, in part, by the lack of a structural
      alteration on 6p. In this report, we describe a pedigree with HFE which carries a
      balanced paracentric inversion of chromosome 6, inv(6)(p21.1p23), a rarely
      reported chromosomal rearrangement in this region. We have determined the
      inheritance of the chromosome harbouring the inversion, which segregates as an
      HFE chromosome. Because the HFE locus has been mapped distal to the HLA-F class I
      locus at 6p21.3, the breakpoints associated with this chromosomal rearrangement
      may provide a significant genomic landmark for positional cloning of the HFE
      gene.

PMID- 9032646
TI  - Recombinations defining centromeric and telomeric borders for the hereditary
      haemochromatosis locus.
AB  - Hereditary haemochromatosis (HFE) is a common inherited disorder, affecting
      approximately five per thousand white people of northern European descent.
      Genetic linkage and linkage disequilibrium studies indicate that the disease
      locus is tightly linked to HLA-A and D6S105. Recombination between HFE and HLA
      class I loci is known to be rare. We report here two pedigrees in which
      recombinations telomeric of HLA-A occurred. These recombinant events define new
      centromeric and telomeric borders for the HFE locus.

PMID- 9032647
TI  - Polymorphic markers of the glycogen debranching enzyme gene allowing linkage
      analysis in families with glycogen storage disease type III.
AB  - Glycogen storage disease type III (GSD-III), an autosomal recessive disease, is
      caused by deficient glycogen debranching enzyme (GDE) activity. We identified
      three polymorphic markers in the GDE gene using single strand conformation
      polymorphism (SSCP) analysis and DNA sequencing. They were -10G/A in the 5' non
      translated region of exon 3,2001 + 8C/T in intron 16, and 3199C/T (P1067S) in
      exon 25. Two polymorphic markers (-10G/A and 2001 + 8C/T) were highly informative
      in both controls and GSD-III patients with heterozygosity values of 0.50 and
      0.46, respectively. The third marker (3199C/T) had a heterozygosity value of
      0.26. Restriction analysis of the PCR amplified genomic DNA products in two GSD
      III families showed for the first time the potential use of these markers for
      carrier detection and prenatal diagnosis in this disease.

PMID- 9032648
TI  - Germline HNPCC gene variants have little influence on the risk for sporadic
      colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is a syndrome of inherited
      bowel and other cancers that has been said to account for up to 15% of all
      colorectal carcinomas (CRCs). HNPCC can now be diagnosed at the molecular level
      by detecting germline mutations in genes involved in mismatch repair. A current
      problem is to determine the prevalence of HNPCC mutations in colon cancer
      patients with limited or no family history, especially in cases of early onset.
      We have identified 50 cases of non-polyposis colorectal cancer without a family
      history of CRC or any other HNPCC cancer, who presented under the age of 45
      years. Germline HNPCC variants (at the hMSH2 or hMLH1 loci) were detected in a
      small minority of cases (6%). The variants that we have found may be new or low
      penetrance mutations, or even polymorphisms. It remains possible that some of our
      sample have an inherited predisposition to CRC that is not caused by HNPCC
      mutations or by known polyposis syndromes. Our data suggest that most HNPCC
      mutations occur in families and have high or moderate penetrance. New or low
      penetrance HNPCC mutations probably do not contribute significantly to the risk
      of colorectal cancer in the general population and probably account for much
      fewer than 15% of all CRCs. Our results question whether mass population genetic
      screening programmes are worthwhile for diseases such as HNPCC using current
      technology.

PMID- 9032649
TI  - Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of
      European descent.
AB  - Charcot-Marie-Tooth type 1 disease (CMT1) and hereditary neuropathy with
      liability to pressure palsies (HNPP) are common inherited disorders of the
      peripheral nervous system. The majority of CMT1 patients have a 1.5Mb tandem
      duplication (CMT1A) in chromosome 17p11.2 while most HNPP patients have a
      deletion of the same 1.5 Mb region. The CMT1A duplication and HNPP deletion are
      the reciprocal products of an unequal crossing over event between misaligned
      flanking CMT1A-REP elements. We analysed 162 unrelated CMT1A duplication patients
      and HNPP deletion patients from 11 different countries for the presence of a
      recombination hotspot in the CMT1A-REP sequences. A hotspot for unequal crossing
      over between the misaligned flanking CMT1A-REP elements was observed through the
      detection of novel junction fragments in 76.9% of 130 unrelated CMT1A patients
      and in 71.9% of 32 unrelated HNPP patients. This recombination hotspot was also
      detected in eight out of 10 de novo CMT1A duplication and in two de novo HNPP
      deletion patients. These data indicate that the hotspot of unequal crossing over
      occurs in several populations independently of ethnic background and is directly
      involved in the pathogenesis of CMT1A and HNPP. We conclude that the detection of
      junction fragments from the CMT1A-REP element on Southern blot analysis is a
      simple and reliable DNA diagnostic tool for the identification of the CMT1A
      duplication and HNPP deletion in most patients.

PMID- 9032650
TI  - Down syndrome: characterisation of a case with partial trisomy of chromosome 21
      owing to a paternal balanced translocation (15;21) (q26;q22.1) by FISH.
AB  - A patient with a typical Down syndrome (DS) phenotype and a normal karyotype was
      studied by FISH. Using painting probes, we found that the patient had partial
      trisomy of chromosome 21 owing to an unbalanced translocation t(15;21) (q26;
      q22.1) of paternal origin. To correlate genotype with phenotype as accurately as
      possible, we localised the breakpoint using a contig of YACs from the long arm of
      chromosome 21 as probes and performed FISH. We ended up with two YACs, the most
      telomeric giving signal on the der (15) in addition to signal on the normal
      chromosome 21 and the most centromeric giving signal only on both normal
      chromosomes 21. From these results we could conclude that the breakpoint must be
      located within the region encompassing YACs 280B1 and 814C1, most likely near one
      end of either YAC or between them, since neither YAC814C1 nor 280B1 crossed the
      breakpoint (most likely between marker D21S304 and marker D21S302) onband
      21q22.1. The same study was performed on the chromosomes of the father and of a
      sister and a brother of the patient; all three carried a balanced translocation
      between chromosomes 15 and 21 and had a normal phenotype. We also performed a
      prenatal study using FISH for the sister. The fetus was also a carrier of the
      balanced translocation.

PMID- 9032651
TI  - Metacarpophalangeal pattern (MCPP) profile analysis in a family with
      triphalangeal thumb.
AB  - Triphalangeal thumb (TPT) is a rare congenital disorder characterised by a long,
      finger-like thumb with three phalanges instead of two. It can occur as an
      isolated defect, in association with other abnormalities of the hands and feet,
      or as a part of a syndrome. Sporadic cases have been described, but it is usually
      inherited as an autosomal dominant trait. In order to examine skeletal morphology
      in different phenotypic variations of this disorder, we performed
      metacarpophalangeal pattern profile analysis in one kindred with this disorder. A
      characteristic profile occurred in all affected people, based on the individual
      lengthening or shortening of the thumb bones. Comparison of the affected and
      unaffected people from this family with people with a different genetic
      background suggests that the described profile is specific for TPT and could be
      used as a helpful diagnostic tool in syndromes which include TPT.

PMID- 9032653
TI  - Carbohydrate deficient glycoprotein (CDG) syndrome type I.

PMID- 9032654
TI  - Fortuitous detection of uniparental isodisomy of chromosome 6.
AB  - Uniparental isodisomy is defined as the inheritance of two copies of the same
      parental chromosome and can result in defects when it produces homozygosity for a
      recessive mutation or in the presence of imprinting. We describe the detection of
      a chromosome 6 uniparental isodisomy in a 9 year old girl, discovered during a
      search for an HLA identical sib. HLA typing, erythrocyte phenotyping, and
      genotypes of microsatellite polymorphisms were compatible with a paternal
      isodisomy of chromosome 6, with normal biparental origin of the other
      chromosomes. Paternal cells were not responsive to the patient's cells in mixed
      lymphocyte cultures. This fortuitous detection of a chromosome 6 isodisomy
      suggests that cases of chromosome 6 UPD may not be deleterious and may therefore
      go undetected.

PMID- 9032652
TI  - Preparing for presymptomatic DNA testing for early onset Alzheimer's
      disease/cerebral haemorrhage and hereditary Pick disease.
AB  - The acceptability of presymptomatic testing in 21 people at 50% risk for the APP
      692 mutation causing presenile Alzheimer's disease or cerebral haemorrhage
      resulting from cerebral amyloid angiopathy (FAD-CH), and in 43 people at 50% risk
      for hereditary Pick disease (HPD) was assessed. Neither group differed in
      demographic variables. Thirty-nine people (64%) in the whole group would request
      presymptomatic testing if it were clinically available, although two-thirds did
      not yet feel ready to take it. The most important reasons in the HPD and FAD-CH
      group for taking the test were: to further basic research (42% and 47%,
      respectively), informing children (47% and 50%, respectively), future planning
      (29% and 47%, respectively), and relieving uncertainty (46% and 27%,
      respectively). The most commonly cited effect of an unfavourable test result
      concerned increasing problems for spouses (75% and 76%, respectively) and
      children (61% and 57%, respectively). Most respondents denied that an
      unfavourable result would have adverse effects on personal mood or relationship.
      One-third of all respondents favoured prenatal testing where one of the parents
      had an increased risk for HPD or FAD-CH. Participants would encourage their
      offspring to have the test before starting a relationship (35%) and before family
      planning (44%). Thirty-seven percent of the respondents would encourage their
      children to opt for prenatal diagnosis. People at risk for HPD were significantly
      more preoccupied with the occurrence of potential symptoms in themselves,
      compared with those at risk for FAD-CH, reflecting the devastating impact that
      disinhibition in the affected patient has on the family. Our findings underline
      the need for adequate counselling and the availability of professional and
      community resources to deal with the impact of test results in subjects and their
      relatives.

PMID- 9032655
TI  - Anal anomalies: an uncommon feature of velocardiofacial (Shprintzen) syndrome?
AB  - We report three cases of velocardiofacial syndrome (VCFS) with anal anomalies who
      have deletions of the 22q11 region and a further case where the proband has VCFS
      clinically and her father has an anal anomaly. It is important to consider VCFS
      in the differential diagnosis of children with anal anomalies and to look for
      other features of the syndrome, such as asymmetrical crying facies, submucous
      cleft of the palate, developmental delay, cardiac anomalies, and
      hypoparathyroidism.

PMID- 9032656
TI  - Gaucher disease: molecular screening of the glucocerebrosidase 1601G and 1601A
      alleles in Victoria, British Columbia, Canada.
AB  - Gaucher disease is the most prevalent lysosomal storage disease and it results
      from inherited deficient glucocerebrosidase activity. The glucocerebrosidase gene
      from normal people was sequenced by several laboratories and it was noted that a
      G or A nucleotide may be present at cDNA position 1601, resulting in 495arginine
      or 495histidine in the glucocerebrosidase polypeptide. In order to rule out the
      possibility of cloning error and to elucidate the genetic status of the two
      genotypes and their distribution in the population, we have developed a
      convenient and reliable method for the molecular screening of the 1601G and 1601A
      genotypes in the population. This method uses PCR amplification of
      glucocerebrosidase genomic DNA in blood samples, followed by BsaHI restriction
      fragment length polymorphism analysis. Out of the 256 subjects without Gaucher
      disease and 15 Gaucher patients surveyed, the 1601G genotype was present in the
      homozygous form in all of the asymptomatic subjects and 14 Gaucher patients. In
      one Gaucher patient who was diagnosed as having type 1 (non-neuropathic) Gaucher
      disease with the A1226G/T1366G mutations, the heterozygous 1601G/A genotype was
      detected. These findings indicate that the 1601G genotype which encodes
      495arginine of the glucocerebrosidase polypeptide is not a cloning error.
      Instead, it constitutes the normal as well as predominant genotype in the
      population in the municipality of Greater Victoria, British Columbia. The 1601A
      genotype, on the other hand, appears to be quite infrequent in this population.
      The availability of our restriction enzyme based method has allowed the screening
      and frequency determination of these two alleles in other populations.

PMID- 9032657
TI  - De novo deletions in spinal muscular atrophy: implications for genetic
      counselling.

PMID- 9032658
TI  - A novel glutamate-mediated inhibitory mechanism linked with Ca2+/calmodulin
      dependent protein kinase II in identified Euhadra neurons.
AB  - The underlying mechanism(s) of the glutamate (Glu)-induced membrane
      hyperpolarizing response in identified Euhadra neurons was investigated using the
      voltage-clamp technique, pressure injection method, and pharmacologic agents.
      Under voltage-clamp conditions, bath-applied Glu elicits a slow outward potassium
      current (Glu current) accompanied by an increase in membrane conductance whose
      amplitude is dose dependent. Of the agonists tested, the Glu current was mimicked
      only by quisqualate (QA); its potency was approximately 10 times greater than
      that of Glu. Typical antagonists for the ionotropic type of Glu receptors and G
      protein inhibitors do not block this current. The Glu current is markedly
      enhanced by a specific inhibitor of Ca2+/ calmodulin-dependent protein kinase II
      (CaM-KII), KN-62 (1-[N,O-bis (1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4
      phenylpiperazine) in a dose-dependent manner, while intracellularly injected CaM
      KII suppresses the current. The potent protein kinase A inhibitors, H-8 (N-[2
      (methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride) and H-89 (N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) or the specific protein
      kinase C inhibitors staurosporine and K-252b had no effect on the Glu current.
      These results suggest the presence of a novel subtype of Glu receptor in Euhadra
      neurons, which may be coupled to the activation of potassium channels normally
      suppressed by CaM-KII.

PMID- 9032659
TI  - Electrically induced changes in Ca2+ in Helisoma neurons: regional and neuron
      specific differences and implications for neurite outgrowth.
AB  - The present experiments addressed the questions of how electrical stimulation
      influenced the magnitude, time course, and regional levels of free intracellular
      calcium of different identified neurons. The calcium concentration in the growth
      cones, neurites and cell bodies of Helisoma buccal neurons B4 and B19 was
      measured while somata were electrically stimulated via an intracellular
      electrode. The findings showed that calcium levels in B4 and B19 increased
      monotonically with increasing stimulation frequency. However, the range of
      calcium levels evoked by electrical stimulation differed significantly for each
      type of neuron. The greater increase in calcium concentration in B4 was
      correlated with its longer duration action potential compared to B19. The
      increase in calcium concentration was much smaller in the cell bodies than in the
      growth cones and neurites. Extending the duration of the B19 action potential
      produced a sixfold increase in the change in calcium concentration at 2 Hz
      stimulation. Under conditions where the electrical stimulation produced a calcium
      concentration of < 160 nM, the elevated level of free intracellular calcium
      remained constant. When calcium concentration increased above 200 nM in both
      identified neurons, an initial peak concentration was followed by a decline to a
      lower concentration suggesting increased calcium buffering occurring above 200
      nM. By correlating the calcium concentration data herein with growth data from a
      previous study, we suggest that specific calcium levels that influence neurite
      outgrowth may differ widely between neurons.

PMID- 9032661
TI  - Okadaic acid reversibly inhibits neurite outgrowth in embryonic dorsal root
      ganglion neurons.
AB  - The aim of this study was to assess the effects of low concentrations of okadaic
      acid (OA) on neurite outgrowth and cellular integrity in cultures of dissociated
      dorsal root ganglion (DRG) neurons. The complete and fully reversible arrest of
      neurite outgrowth was achieved at 1 nM OA, thus ruling out the involvement of
      protein phosphatase 1 in the observed inhibitory effect. OA at 0.5 nM did not
      completely block neurite outgrowth, although it reduced the rate of growth by
      about one third. Protein phosphorylation and the integrity of microtubules and
      neurofilaments in neuron-enriched cultures were unaffected by 1 nM OA. The rate
      of synthesis of the low-molecular-weight neurofilament subunit (NFL) was also
      unchanged by OA treatment. Antimitotic agents used to eliminate proliferating
      cells did not alter the rate of neurite elongation. Since 1 nM OA does not
      suffice to inhibit neuronal protein phosphatase 2A fully, owing to the high
      concentration of this enzyme in neurons, we propose that the inhibitor is
      affecting a neuronal compartment that contains low levels of the phosphatase.
      This putative compartment is likely to be located in neurites, which were shown
      to contain levels of protein phosphatase 2A that were two- to threefold lower
      than in neuronal perikarya.

PMID- 9032660
TI  - Distribution of cholinergic neuronal differentiation factor/leukemia inhibitory
      factor binding sites in the developing and adult rat nervous system in vivo.
AB  - Cholinergic neuronal differentiation factor/leukemia inhibitory factor (CDF/LIF)
      is a multifunctional cytokine that affects neurons as well as many other cell
      types. Toward elucidating its neural functions in vivo, we previously
      investigated the distribution of CDF/LIF binding sites with iodinated native
      CDF/LIF in embryonic to postnatal day 0 (P0) rats. In the present study, we have
      extended our examination to postnatal ages and find that specific CDF/LIF binding
      sites are present at defined developmental stages in additional brain regions not
      previously exhibiting binding by P0. High levels of binding are detected in all
      P7 sensory and autonomic ganglia examined, but only in restricted postnatal
      central nervous system structures. Cranial motor and mesencephalic trigeminal
      neurons maintain high levels throughout, while binding to spinal motor neurons,
      which decreases to low levels at P0, reappears by P14 and increases with age.
      Most other structures, which show detectable binding by P0, exhibit higher levels
      at postnatal ages, including the red, deep, ventral cochlear, trapezoid, superior
      olivary, vestibular, ventral tegmental, and ventral posterior thalamic nuclei as
      well as the glomerular layer of the olfactory bulb. High levels are also detected
      in several structures for the first time after P0, including the cerebellar
      cortex (molecular and Purkinje cell layers), lateral reticular nucleus of the
      medulla and reticular formation, as well as the reticulotegmental, medial
      geniculate, solitary (rostral, dorsomedial, and commissural regions), medial
      septal, lateral mammillary, and lateral habenular nuclei. These results not only
      identify regions of potential CDF/LIF-responsive neurons and glia throughout
      development but suggest new CDF/LIF roles in the nervous system.

PMID- 9032662
TI  - Growth hormone, insulin-like growth factor I, and motoneuron size.
AB  - In this study we asked whether growth hormone (GH) and one of its key mediators,
      insulin-like growth factor I (IGF-I), influence spinal motoneuron size in
      conjunction with whole body size. We present evidence that GH has such a role,
      possibly without the mediation of IGF-I. Both lumbar motoneuron and body size
      were found to be increased relative to littermate controls in transgenic mice
      overexpressing GH, while body size, but not motoneuron size, was increased in
      mice overexpressing IGF-I. GH overexpression coordinately increased nucleolar,
      nuclear, and cell body size in lumbar spinal motoneurons, so that their normal
      size relationships were preserved in the transgenic mice. In addition, spinal
      cord and brain weights were significantly increased in both types of transgenic
      animal. We conclude that GH can regulate motoneuron, central nervous system, and
      body size in the same animal, and that IGF-I can mimic the effects of GH on at
      least two of these three parameters.

PMID- 9032663
TI  - Metamorphic remodeling of the primary olfactory projection in Xenopus:
      developmental independence of projections from olfactory neuron subclasses.
AB  - In adult Xenopus, the nasal cavity is divided into separate middle (MC) and
      principal (PC) cavities; the former is used to smell water-borne odorants, the
      latter air-borne odorants. Recent work has shown that olfactory neurons of each
      cavity express a distinct subclass of odorant receptors. Moreover, MC and PC
      axons project to distinct regions of the olfactory bulb. To examine the
      developmental basis for this specificity in the olfactory projection, we
      extirpated the developing MC from early metamorphic (stage 54-57) tadpoles and
      raised the animals through metamorphosis. In most lesioned animals, the MC partly
      regenerated. Compared with the unlesioned side, reduction of the region of the
      glomerular layer of the olfactory bulb receiving MC afferents ranged from 70% to
      95%. PC afferents did not occupy regions of the olfactory bulb deprived of MC
      afferents. These results support a model in which intrinsic cues in the olfactory
      bulb control the projection pattern attained by ingrowing olfactory axons.

PMID- 9032664
TI  - Development of polarity in cerebellar granule neurons.
AB  - Axon formation in developing cerebellar granule neurons in situ is spatially and
      temporally segregated from subsequent neuronal migration and dendrite formation.
      To examine the role of local environmental cues on early steps in granule cell
      differentiation, the sequence of morphologic development and polarized
      distribution of membrane proteins was determined in granule cells isolated from
      contact with other cerebellar cell types. Granule cells cultured at low density
      developed their characteristic axonal and dendritic morphologies in a series of
      discrete temporal steps highly similar to those observed in situ, first extending
      a unipolar process, then long, thin bipolar axons, and finally becoming
      multipolar, forming short dendrites around the cell body. Axonal- and dendritic
      specific cytoskeletal markers were segregated to the morphologically distinct
      domains. The cell surface distribution of a specific class of endogenous
      glycoproteins, those linked to the membrane by a glycosylphosphatidyl inositol
      (GPI) anchor, was also examined. The GPI-anchored protein, TAG-1, which is
      segregated to the parallel fiber axons in situ, was found exclusively on granule
      cell axons in vitro; however, two other endogenous GPI-anchored proteins were
      found on both the axonal and somatodendritic domains. These results demonstrate
      that granule cells develop polarity in a cell type-specific manner in the absence
      of the spatial cues of the developing cerebellar cortex.

PMID- 9032665
TI  - Axonal transport of synaptic vesicle proteins in the rat optic nerve.
AB  - The optic nerve, as a part of the central nervous system (CNS), has been used to
      study axonal transport for decades. The present study has concentrated on the
      axonal transport of synaptic vesicle proteins in the optic nerve, using the "stop
      flow/nerve crush" method. After blocking fast axonal transport, distinct
      accumulations of synaptic vesicle proteins developed during the first hour after
      crush-operation and marked increases were observed up to 8 h postoperative.
      Semiquantitative analysis, using cytofluorimetric scanning (CFS) of
      immunoincubated sections, revealed that the ratio between distal accumulations
      (organelles in retrograde transport) and proximal accumulations (organelles in
      anterograde transport) was much higher (up to 80-90%) for the transmembrane
      proteins than that for surface adsorbed proteins (only 10-20%). The pattern of
      axonal transport in the optic nerve was comparable to that in the sciatic nerve.
      However, clathrin and Rab3a immunoreactivities were accumulated in much lower
      amounts than that in the sciatic nerve. Most synaptic vesicle proteins were
      colocalized in the axons proximal to the crush. A differential distribution of
      synaptobrevin I and II, however, was observed in the optic nerve axons;
      synaptobrevin I was present in large-sized axons, while synaptobrevin II
      immunoreactivity was present in most axons, including the large ones. The two
      isoforms were, thus, partially colocalized. The results demonstrate that (1)
      cytofluorimetric scanning techniques could be successfully used to study axonal
      transport not only in peripheral nerves, but also in the CNS; (2) synaptic
      vesicles are transported with fast axonal transport in this nerve; and (3) some
      differences were noted compared with the sciatic nerve, especially for Rab3a and
      clathrin.

PMID- 9032679
TI  - Spatiotemporal gradients of intra-axonal [Na+] after transection and resealing in
      lizard peripheral myelinated axons.
AB  - 1. Post-transection changes in intracellular Na+ ([Na+]i) were measured in lizard
      peripheral axons ionophoretically injected with the Na(+)-sensitive ratiometric
      dye, sodium-binding benzofuran isophthalate (SBFI). 2. Following axonal
      transection in physiological saline [Na+]i increased to more than 100 mM in a
      region that quickly extended hundreds of micrometers from the transection site.
      This post-transection increase in [Na+]i was similar when the bath contained 5
      microM tetrodotoxin, but was absent in Na(+)-free solution. Depolarization of
      uncut axons in 50 mM K+ produced little or no elevation of [Na+]i until
      veratridine was added. These results suggest that the post-transection increase
      in [Na+]i was due mainly to Na+ entry via the cut end, rather than via
      depolarization-activated Na+ channels. 3. The spatiotemporal profile of the post
      transection increase in [Na+]i could be accounted for by movement of Na+ from the
      cut end with an apparent diffusion coefficient of 1.3 x 10(-5) cm2 s-1. 4. [Na+]i
      began to decline toward resting levels by 20 +/- 15 min (mean +/- S.D.) post
      transection, except in regions of the axon within 160 +/- 85 microns of the
      transection site, where [Na+]i remained high. The boundary between axonal regions
      in which [Na+]i did or did not recover probably defines a locus of resealing of
      the axonal membrane. 5. [Na+]i returned to resting values within about 1 h after
      resealing, even in axonal regions where the normal transmembrane [Na+] gradient
      had completely dissipated. The recovery of [Na+]i was faster and reached lower
      levels than expected by diffusional redistribution of Na+ along the axon. Partial
      recovery occurred even in an isolated internode, indicating that the internodal
      axolemma can actively extrude Na+.

PMID- 9032680
TI  - Modulation of the human cardiac sodium channel alpha-subunit by cAMP-dependent
      protein kinase and the responsible sequence domain.
AB  - 1. In order to investigate the modulation of human hH1 sodium channel alpha
      subunits by cAMP-dependent protein kinase (PKA), the channel was expressed in
      oocytes of Xenopus laevis. 2. Cytosolic injection of cAMP, as well as of SP
      cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (SP-cAMPS,
      the S-diastereoisomeric configuration of the compound with respect to the
      phosphorus atom), resulted in a marked and significant increase in peak sodium
      current (INa,p). Cytosolic injections of RP-cyclic 3',5'-hydrogen
      phosphorothioate adenosine triethylammonium salt (RP-cAMPS; a compound inhibitory
      to PKA) had no effect on peak current. 3. Kinetic parameters of steady-state
      activation, inactivation and recovery from inactivation were unchanged following
      stimulation of PKA activity, but a 42 +/- 5% (mean +/- S.E.M.) increase in
      maximal sodium conductance (delta gmax) could account for the observed increase
      in INa,p. 4. A set of chimerical sodium channels made from portions of the human
      cardiac hH1 alpha-subunit and the rat skeletal muscle SkM1 alpha-subunit (which
      is not affected by PKA stimulation) was generated. These were used to localize
      the structural determinant in the hH1 sequence responsible for PKA modulation of
      hH1. From our data we conclude that the effects of PKA on hH1 are conferred by
      the large cytosolic loop interconnecting transmembrane domains I and II, which is
      not conserved among sodium channel subtypes.

PMID- 9032681
TI  - Similarity of ATP-dependent K+ channels in skeletal muscle fibres from normal and
      mutant mdx mice.
AB  - 1. ATP-dependent K+ (KATP) channels were studied in fibres isolated from flexor
      digitorum brevis and interosseal skeletal muscles of normal and mutant mdx mice
      using the patch clamp technique in the presence of asymmetrical K+ concentrations
      (5 mM K+ in the pipette and in vivo intracellular [K+] or 145 mM K+ at the
      cytoplasmic face). 2. In cell-attached patches from mdx muscle fibres bathed in
      K(+)-rich solution, cell poisoning with fluorodinitrobenzene induced partially
      reversible opening of channels carrying an outward current of an amplitude of 1.2
      pA at 0 mV. Exposure of fibres to the K+ channel opener cromakalim led to opening
      of the same type of channel. These channels were assumed to be KATP channels. 3.
      On excision of inside-out patches from mdx muscle fibres, in the absence of
      intracellular ATP, KATP channels were active: they carried a unitary outward
      current of 1.6 pA at 0 mV and were inhibited by intracellular ATP and
      glibenclamide. The number of KATP channels per patch was not significantly
      different in muscles from normal and mdx mice. 4. In inside-out patches, in the
      presence of 1 mM intracellular Mg2+, slope conductances of 21 and 20.3 pS were
      found for KATP channels in normal and mdx muscle, respectively. In the absence of
      Mg2+, slope conductances of KATP channels were 31.3 and 32 pS in normal and mdx
      muscle, respectively and KATP channel activity was augmented in mdx muscle in the
      same way as in normal muscle. Activity of the same KATP channel was observed in
      extensor digitorum longus muscle from normal and mdx mice. 5. In inside-out
      patches held at 0 mV, the relationship between KATP channel activity and
      intracellular ATP was described by a Hill equation: Ki values were 23 and 21
      microM and Hill coefficients were 1.8 and 1.9 in normal and mdx muscle,
      respectively. 6. These results indicate that the distribution, the conductance
      properties and ATP sensitivity of KATP channels do not differ in normal and in
      mdx mouse skeletal muscle.

PMID- 9032682
TI  - Muscarinic and nicotinic receptors raise intracellular Ca2+ levels in rat carotid
      body type I cells.
AB  - 1. The effects of cholinergic agonists upon intracellular free Ca2+ levels
      ([Ca2+]i) have been studied in enzymically isolated rat carotid body single type
      I cells, using indo-1. 2. Acetylcholine (ACh) dose-dependently increased [Ca2+]i
      in 55% of cells studied (EC50 = 13 microM). These [Ca2+]i rises were partially
      inhibited by atropine or mecamylamine. 3. Specific nicotinic and muscarinic
      agonists also elevated [Ca2+]i in a dose-dependent manner (nicotine, EC50 = 15
      microM; methacholine, EC50 = 20 microM). 4. While the majority of the ACh
      sensitive cells responded to both classes of cholinergic agonist, 29% responded
      exclusively to nicotinic stimulation and 9% responded exclusively to muscarinic
      stimulation. 5. In the presence of nicotinic agonists, Ca2+i responses were
      transient. In the presence of muscarinic agonists, Ca2+i responses consisted of
      an initial rise, which then declined to a lower plateau level. 6. Nicotinic
      responses were rapidly abolished in Ca(2+)-free medium, suggesting that they are
      dependent on Ca2+ influx. 7. The plateau component of the muscarinic-activated
      response was also abolished in Ca(2+)-free conditions. The rapid initial [Ca2+]i
      rise, however, could still be evoked after several minutes in Ca(2+)-free medium.
      Muscarine also increased Mn2+ quenching of intracellular fura-2 fluorescence.
      These data suggest that the full muscarinic response depends on both Ca2+ release
      from intracellular stores and Ca2+o influx. 8. The results indicate that, in rat
      carotid body type I cells, both nicotinic and muscarinic acetylcholine receptors
      increase [Ca2+]i, but achieve this via different mechanisms. ACh may therefore
      play a role in carotid body function by modulating Ca2+i in the chemosensory type
      I cells.

PMID- 9032683
TI  - Ca2+ release from internal stores: role in generating depolarizing after
      potentials in rat supraoptic neurones.
AB  - 1. Influences of Ca2+ release from internal stores on the generation of
      depolarizing after-potentials (DAPs) were investigated in magnocellular neurones
      of rat supraoptic nucleus (SON) using whole-cell patch recording techniques in
      brain slices. 2. DAPs were recorded from more than half of the cells encountered,
      and following evoked single spikes had an amplitude of 3.00 +/- 0.19 mV (mean +/-
      S.E.M.) and lasted for 1.02 +/- 0.06 s. Their sizes usually increased with the
      number of preceding spikes, but could be reduced or eliminated when intervals
      between consecutive current pulses evoking tens of spikes were short. 3. DAPs
      were eliminated by removal of external Ca2+, and significantly reduced by bath
      application of nifedipine or omega-conotoxin. 4. Blockade of Ca2+ release from
      internal stores by perifusion with ryanodine or dantrolene, or direct diffusion
      of Ruthenium Red into cells suppressed DAP amplitudes by approximately 50% and
      shortened their durations. 5. Depletion of internal Ca2+ stores by perifusion
      with thapsigargin or cyclopiazonic acid also reduced DAP amplitudes by
      approximately 50% and eliminated phasic patterns of firing. 6. Caffeine, an agent
      known to enhance intracellular Ca2+ release, amplified DAPs and promoted phasic
      firing. 7. These results suggest that Ca2+ influx via high-voltage-activated Ca2+
      channels in SON cells triggers ryanodine receptor-mediated Ca2+ release from
      internal stores. This process enhances DAPs and promotes phasic firing in SON
      cells, and would thus contribute to vasopressin release.

PMID- 9032684
TI  - Delayed autoregulation of the Ca2+ signals resulting from capacitative Ca2+ entry
      in bovine pulmonary artery endothelial cells.
AB  - 1. In calf pulmonary artery endothelial (CPAE) cells loaded with fura-2, the
      effects of ATP on Ca2+ entry were mediated entirely by the ability of P2U
      purinoceptors to stimulate InsP3 formation, empty intracellular Ca2+ stores and
      thereby activate capacitative Ca2+ entry. 2. Restoration of extracellular Ca2+ to
      cells with empty intracellular stores evoked transient increases in cytosolic
      [Ca2+] ([Ca2+]i) which then declined to an elevated plateau. These overshoots in
      [Ca2+]i were not a consequence of store refilling nor of desensitization of the
      capacitative pathway. Similar responses were recorded from cells in which Ca2+
      uptake into mitochondria had been inhibited by microinjection of Ruthenium Red.
      The amplitudes of the capacitative Ca2+ signals decreased at lower extracellular
      [Ca2+], but [Ca2+]i invariably overshot before slowly declining to an elevated
      plateau. Even modest increases in [Ca2+]i therefore caused a delayed attenuation
      of the Ca2+ signal evoked by capacitative Ca2+ entry. 3. Modest pre-elevation of
      [Ca2+]i inhibited the ability of subsequent capacitative Ca2+ entry to further
      increase [Ca2+]i. The onset of the inhibition was slow (half-time (t1/2),
      approximately 100 s) and more tightly correlated with the preceding peak [Ca2+]i
      than with the [Ca2+]i immediately preceding Ca2+ entry. Recovery was also slow
      and complete only after [Ca2+]i had returned to its basal level for 320 +/- 3 s.
      4. In thapsigargin-treated cells loaded with mag-fura-2, the peak [Ca2+]i that
      followed restoration of extracellular Ca2+ was accompanied by an abrupt
      approximately 2.5-fold decrease in the rate of Mn2+ entry, which then continued
      indefinitely at the reduced rate, demonstrating a rapid partial inactivation of
      the capacitative pathway. 5. The half-time for Ca2+ removal from the cytosol was
      significantly slower during the rising (t 1/2 = 22 +/- 2.5 s) than during the
      falling (t 1/2 = 7.1 +/- 0.7 s) phase of the Ca2+ overshoot evoked by addition of
      extracellular Ca2+ to thapsigargin-treated cells. 6. We conclude that an increase
      in [Ca2+]i rapidly inhibits the capacitative pathway and more slowly activates
      mechanisms that remove Ca2+ from the cytosol. Reversal of either or both of these
      regulatory mechanisms can occur only a considerable time after [Ca2+]i has been
      completely restored to its resting level. These mechanisms are likely to protect
      cells from excessive increases in [Ca2+]i and contribute to oscillatory changes
      in [Ca2+]i.

PMID- 9032685
TI  - Myogenic contraction by modulation of voltage-dependent calcium currents in
      isolated rat cerebral arteries.
AB  - 1. Tissue blood flow and blood pressure are regulated by the spontaneous,
      myogenic, contraction developed by resistance arteries. However, the cellular
      mechanisms underlying myogenic contraction are not understood. In this study, the
      mechanisms of myogenic contraction in cerebral resistance arteries were
      investigated. 2. The vasoconstriction observed in response to increased pressure
      in cerebral resistance arteries (myogenic reactivity) was dependent on Ca2+ entry
      through voltage-dependent Ca2+ channels, since it was abolished by Ca2+ removal
      and by dihydropyridine antagonists of voltage-dependent Ca2+ channels. 3.
      Myogenic reactivity persisted in a high-K+ saline, with reduced Ca2+, where
      membrane potential is presumed to be clamped. Therefore, membrane depolarization
      alone does not fully account for the increased voltage-dependent Ca2+ channel
      opening. 4. Voltage-dependent Ca2+ currents in single smooth muscle cells
      isolated from the resistance artery were substantially increased by applying
      positive pressure to the patch electrode evoking membrane stretch. 5. Myogenic
      reactivity remained unaffected by ryanodine and therefore was independent of
      internal ryanodine-sensitive Ca2+ stores. 6. The myofilament Ca2+ sensitivity was
      not increased by elevated pressure in alpha-toxin-permeabilized arteries.
      However, pharmacological activation of protein kinase C or G proteins did
      increase the myofilament Ca2+ sensitivity. 7. Myogenic contraction over the
      pressure range 30-70 mmHg could be accounted for by an increase in [Ca2+]i from
      100 to 200 nM. 8. It is concluded that modest increases in [Ca2+]i within the
      range 100-200 nM can account for that myogenic contraction, and that stretch
      evoked modulation of Ca2+ currents may contribute to the myogenic response.

PMID- 9032686
TI  - Calcium-activated chloride channels in bovine pulmonary artery endothelial cells.
AB  - 1. We characterized Ca(2+)-activated Cl- currents in calf pulmonary artery
      endothelial (CPAE) cells by using a combined patch clamp and fura-2
      microfluorescence technique to simultaneously measure ionic currents and the
      intracellular Ca2+ concentration, [Ca2+]i. 2. Various procedures that increased
      [Ca2+]i, such as stimulation with ATP or ionomycin, or loading the cells with
      Ca2+ via the patch pipette, activated a strongly outwardly rectifying current
      with a reversal potential close to the Cl- equilibrium potential. Changing the
      extracellular Cl- concentration shifted this reversal potential as predicted for
      a Cl- current. Buffering Ca2+ rises with BAPTA prevented ATP from activating the
      current. 3. Ca(2+)-activated Cl- currents could be distinguished from volume
      activated Cl- currents, which were sometimes coactivated in the same cell. The
      latter showed much less outward rectification, their activation was voltage
      independent, and they could be inhibited by exposing the cells to hypertonic
      solutions. 4. The permeability ratio for the Ca(2+)-activated conductance of the
      anions iodide:chloride: gluconate was 1.71 +/- 0.06:1:0.39 +/- 0.03 (n = 12). 5.
      This Ca(2+)-activated Cl- current, ICl, Ca, inactivated rapidly at negative
      potentials and activated slowly at positive potentials. Outward tail currents
      were slowly decaying, while inward tail currents decayed much faster. 6. 4,4'
      Diisothiocyanatostilbene-2,2'-disulphonic-acid (DIDS) and niflumic acid inhibited
      Icl,Ca in a voltage-dependent manner, i.e. they exerted a more potent block at
      positive potentials. The block by N-phenylanthracilic acid (NPA), 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB) and tamoxifen was voltage independent.
      Niflumic acid and tamoxifen were the most potent blockers. 7. The single-channel
      conductance was 7.9 +/- 0.7 pS (n = 15) at 300 mM extracellular Cl-. The channel
      open probability was high at positive potentials, but very small at negative
      potentials. 8. It is concluded that [Ca2+]i activates small-conductance Cl-
      channels in endothelial cells, which coexist with the volume-activated Cl-
      channels described previously.

PMID- 9032687
TI  - Calcium-activated chloride current in normal mouse sympathetic ganglion cells.
AB  - 1. In rat sympathetic ganglion cells, axotomy induces the appearance of a
      depolarizing after-potential (ADP) produced by a calcium-activated chloride
      current. Here we report that this current is also present in normal sympathetic
      neurones from the mouse. 2. In an in vitro preparation of the superior cervical
      ganglion, an ADP was observed after spike firing in 50% of the cells studied with
      single-electrode current- and voltage-clamp techniques. 3. When the cells were
      voltage clamped at -50 mV in the presence of tetrodotoxin (TTX) and
      tetraethylammonium chloride (TEA), depolarizing jumps evoked inward calcium
      currents which were contaminated by outward chloride currents, followed by slowly
      decaying inward chloride tail currents. 4. The ADP and the inward tail currents
      disappeared when calcium was removed from the extracellular solution or when
      cadmium was added. 5. The reversal potential for the inward tail current was
      approximately -24 mV and was displaced in agreement with the Nernst equation for
      chloride when the extracellular NaCl was replaced by sucrose or sodium
      isethionate. The chloride channel blocker anthracene-9-carboxylic acid (9AC)
      inhibited both the ADP and the tail current. 6. Using intracellular injection of
      neurobiotin, we found that cells with shorter dendrites had larger ADPs. In
      axotomized ganglia practically all cells showed very pronounced ADPs. 7. We
      conclude that normal mouse sympathetic ganglion cells have a calcium-activated
      chloride current that generates an ADP. The channels responsible for this current
      are probably located in the dendrites.

PMID- 9032688
TI  - Regulation of an outwardly rectifying Cl- conductance in single proximal tubule
      cells isolated from frog kidney.
AB  - 1. A previous study has identified a Cl- conductance (GCl) in single proximal
      tubule cells isolated from frog kidney, which was activated by a protein kinase C
      (PKC)-dependent mechanism. 2. The whole-cell patch clamp technique was employed
      to examine further the properties and regulation of GCl. 3. GCl showed outward
      rectification, outward conductance was significantly greater than the inward
      conductance (56.1 +/- 15.6 vs. 16.8 +/- 6.4 microS cm-2, respectively, n = 8).
      DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) blocked GCl in a dose-
      and voltage-dependent manner. 4. Other anions permeated the conductance. The
      anion selectivity sequence, I- > Br- > Cl- > gluconate, followed Eisenman's
      sequence I. 5. GCl could be activated by ATP. This process was dependent on ATP
      hydrolysis and channel phosphorylation. 6. G-protein activation inhibited the ATP
      dependent activation of GCl. 7. These data support the hypothesis that activation
      of GCl by an increase in cell volume is dependent on ATP hydrolysis and channel
      phosphorylation via PKC.

PMID- 9032689
TI  - A novel mechanosensitive cationic channel from the endothelium of rat aorta.
AB  - 1. Single channel currents were recorded from the lumenal surface of endothelium
      of excised intact rat aorta using the patch clamp technique. 2. The majority of
      cell-attached and inside-out patches contained cationic channels with an equal
      permeability to Na+ and K+. Positive pressure applied through the pipette
      reversibly increased their open probability, whereas negative pressure reversibly
      decreased it. The dependence of the channel activity on pressure was sigmoidal in
      all tested patches. 3. The slope conductance of the channel for inward current
      was 33.9 +/- 2.1 pS in a nominally Ca(2+)-free extracellular solution. With 1 mM
      CaCl2 in the extracellular solution, the channel conductance for inward current
      was reduced to 21.2 +/- 2.3 pS. In isotonic CaCl2 solution, the slope conductance
      of the channel was 5.9 +/- 1.3 pS. The ionic permeability ratio was PCa: PNa: PK
      = 3.5:1:1. 4. Gadolinium and lanthanum at a concentration of 10 microM did not
      affect the channels, but at higher concentrations (> or = 100 microM) reduced
      inward currents through the channels. 5. The mechanosensitive channel reported
      here is different in its gating mechanism and pharmacology from stretch-activated
      channels described previously. This channel may be involved in
      mechanotransduction of haemodynamic stimuli in endothelium.

PMID- 9032690
TI  - An ATP-gated cation channel with some P2Z-like characteristics in gastric smooth
      muscle cells of toad.
AB  - 1. Whole-cell and single-channel currents elicited by extracellular ATP were
      studied in freshly dissociated smooth muscle cells from the stomach of the toad
      Bufo marinus using standard patch clamp and microfluorimetric techniques. 2. This
      ATP-gated cation channel shares a number of pharmacological and functional
      properties with native rat myometrium receptors, certain native P2Z purinoceptors
      and the recently cloned P2X7 purinoceptor. But, unlike the last two, the ATP
      gated channel does not mediate the formation of large non-specific pores. Thus,
      it may represent a novel member of the P2X or P2Z class. 3. Extracellular
      application of ATP (> or = 150 microM) elicited an inward whole-cell current at
      negative holding potentials that was inwardly rectifying and showed no sign of
      desensitization. Na+, Cs+ and, to a lesser degree, the organic cation choline
      served as charge carriers, but Cl- did not. Ratiometric fura-2 measurements
      indicated that the current is carried in part by Ca2+. The EC50 for ATP was 700
      microM in solutions with a low divalent cation concentration. 4. ATP (> or = 100
      microM) at the extracellular surface of cell-attached or excised patches elicited
      inwardly rectifying single-channel currents with a 22 pS conductance. Cl- did not
      serve as a charge carrier but both Na+ and Cs+ did, as did choline to a lesser
      extent. The mean open time of the channel was quite long, with a range in
      hundreds of milliseconds at a holding potential of -70 mV. 5. Mg2+ and Ca2+
      decreased the magnitude of the ATP-induced whole-cell currents. Mg2+ decreased
      both the amplitude and the activity of ATP-activated single-channel currents. 6.
      ADP, UTP, P1, P5-di-adenosine pentaphosphate (AP5A), adenosine and alpha, beta
      methylene ATP (alpha, beta-Me-ATP) did not induce significant whole-cell current.
      ATP-gamma-S and 2-methylthio ATP (2-Me-S-ATP) were significantly less effective
      than ATP in inducing whole-cell currents, whereas benzoylbenzoyl ATP (BzATP) was
      more effective. BzATP, alpha, beta-Me-ATP, ATP-gamma-S and 2-Me-S-ATP induced
      single-channel currents, but a higher concentration of alpha, beta-Me-ATP was
      required. 7. BzATP did not induce the formation of large non-specific pores, as
      assayed using mag-fura-2 as a high molecular mass probe.

PMID- 9032691
TI  - Dynamic properties of nitric oxide release from parallel fibres in rat cerebellar
      slices.
AB  - 1. Nitric oxide (NO) release following repetitive electrical stimulation was
      studied in the molecular layer of rat cerebellar slices using electrochemical NO
      probes. 2. In parasagittal slices of the vermis, most Purkinje cells showed
      climbing fibre responses in response to white matter stimulation without
      accompanying NO release. 3. In frontal slices, parallel fibre volley potentials
      and NO release were elicited concurrently by parallel fibre stimulation. 4. The
      NO release following parallel fibre stimulation was not affected by blockers of
      non-NMDA, NMDA and metabotropic glutamate receptors. 5. The NO release was
      reduced significantly (P < 0.001) to 29% of the control level after climbing
      fibre deafferentation with 3-acetylpyridine treatment. 6. The rate of NO release
      was roughly proportional to the second or third power of the stimulus frequency,
      and to the third power of the extracellular Ca2+ concentration. 7. The rate of NO
      release was not affected by nicardipine (10 microM). It was reduced to 87 +/- 4%
      (n = 5, mean +/- S.E.M.) of the control level by omega-conotoxin GVIA (0.3
      microM), and to 18 +/- 4% (n = 4) by omega-agatoxin IVA (0.3 microM). 8. Tetanic
      parallel fibre stimulation potentiated NO release by 24 +/- 5% (n = 5). 9. These
      data indicate that NO is derived mainly from parallel fibres. The relationship
      between NO release and cerebellar synaptic plasticity is discussed.

PMID- 9032692
TI  - Inhibition of nitroxidergic nerve function by neurogenic acetylcholine in monkey
      cerebral arteries.
AB  - 1. Modification by endogenous or exogenous acetylcholine and vasoactive
      intestinal polypeptide (VIP) of vasodilatation mediated by nitric oxide (NO)
      released from nitroxidergic nerves was studied in isolated monkey cerebral
      arteries. In arterial strips denuded of endothelium, transmural electrical
      stimulation (2-20 Hz) produced relaxations that were abolished by tetrodotoxin.
      2. The relaxation response was attenuated by acetylcholine, and the attenuation
      was reversed by atropine. Attenuation was also observed with AF-DX 116, an
      antagonist of the muscarinic acetylcholine receptor subtype, M2. NO-induced
      relaxation was not affected by acetylcholine. Neurogenic relaxation was also
      inhibited by physostigmine and potentiated by atropine. 3. VIP in concentrations
      that elicited slight relaxation did not alter the response to nerve stimulation.
      In the strips showing tachyphylaxis to VIP, the neurogenic response was not
      inhibited. 4. Histochemical studies of whole-mount preparations revealed nerve
      fibres with NO synthase and VIP immunoreactivity, and also acetylcholinesterase,
      suggesting the presence of perivascular nitroxidergic, VIPergic and cholinergic
      innervation. 5. It is concluded that the actions of nitroxidergic nerve fibres on
      the monkey cerebral artery are inhibited by nerve-released acetylcholine acting
      on prejunctional muscarinic receptors, possibly of the M2 subtype. Despite the
      presence of VIP immunoreactive nerve fibres and the ability of exogenous VIP to
      relax the artery, there is no evidence supporting either a prejunctional
      modulation of nitroxidergic nerve function by VIP or a role for VIP as a
      vasodilatory neurotransmitter.

PMID- 9032693
TI  - Presynaptic inhibitory action of opioids on synaptic transmission in the rat
      periaqueductal grey in vitro.
AB  - 1. The actions of opioids on synaptic transmission in rat periaqueductal grey
      (PAG) neurones were examined using whole-cell patch-clamp recordings in brain
      slices. 2. Methionine enkephalin (ME; 10 microM) inhibited evoked GABAergic
      inhibitory postsynaptic currents (IPSCs) by 57%, non-NMDA excitatory postsynaptic
      currents (EPSCs) by 60%, and NMDA EPSCs by 43% in PAG neurones. This inhibition
      was associated with an increase in paired-pulse facilitation, was mimicked by the
      mu-agonist DAMGO (1-3 microM) and abolished by naloxone (1 microM). Neither the
      kappa-agonist U69593 (1-3 microM), nor the delta-agonist DPDPE (3-10 microM) had
      any specific actions on evoked PSCs. 3. ME decreased the frequency of spontaneous
      miniature, action potential-independent postsynaptic currents (mIPSCs by 65%,
      mEPSCs by 54%) in all PAG neurones, but had no effect on their amplitude
      distributions. The reduction in mIPSC frequency persisted in nominally Ca(2+)
      free, high-Mg2+ (10 mM) solutions, which also contained Cd2+ (100 microM), or
      Ba2+ (10 mM). Opioid inhibition of mIPSC frequency is unlikely to be mediated by
      presynaptic Ca2+ or K+ conductances which are sensitive to extracellular Cd2+ or
      Ba2+. 4. In a subpopulation of PAG neurones, ME increased a Ba(2+)-sensitive K+
      conductance at potentials below -97 mV. Opioids inhibited both GABAergic and
      glutamatergic synaptic transmission in all PAG neurones, independent of any
      postsynaptic opioid sensitivity. 5. These observations are consistent with, but
      only partially support, the opioid disinhibition model of PAG-induced analgesia.
      mu-Opioids also have the potential to modulate the behavioural and autonomic
      functions of the PAG via modulation of both inhibitory and excitatory presynaptic
      mechanisms, as well as postsynaptic mechanisms.

PMID- 9032694
TI  - Vagal branches involved in inhibition of bradykinin-induced synovial plasma
      extravasation by intrathecal nicotine and noxious stimulation in the rat.
AB  - 1. Stimulation of cutaneous and spinal visceral nociceptive afferents and
      intrathecal nicotine reduces bradykinin-induced plasma extravasation (BK-induced
      PE) in the knee joint of the rat. This depression is mediated by the hypothalamo
      pituitary-adrenal (HPA) axis and is potentiated by subdiaphragmatic vagotomy. It
      is believed that activity in vagal afferents tonically inhibits ascending impulse
      transmission in the neuraxis projecting to the hypothalamus. Vagotomy, by
      removing such inhibition, allows greater depression of BK-induced PE. In this
      study we determined whether the vagal afferents which negatively regulate
      activities of the HPA axis are present in all branches of the abdominal vagus
      nerves or only in specific branches. 2. We measured the depression of BK-induced
      PE elicited by graded stimulation of spinal visceral afferents with
      intraperitoneal capsaicin and by intrathecal nicotine in vagus-intact rats and in
      rats in which specific vagal branches were selectively interrupted. (i)
      Interruption of the coeliac branches mimicked the effect of total
      subdiaphragmatic vagotomy in potentiating the depression of BK-induced PE
      generated by intrathecal nicotine and by stimulation of spinal visceral
      afferents. (ii) Interruption of the gastric and hepatic branches of the abdominal
      vagus nerves together or individually did not affect the depression of BK-induced
      PE generated by the two stimuli. 3. These results indicate that afferent activity
      in coeliac and accessory coeliac vagal branches is involved in the regulation of
      the nociceptive system-initiated depression of BK-induced PE. The afferent fibres
      in these vagal branches involved probably monitor physiological events in
      abdominal visceral organs.

PMID- 9032695
TI  - Temperature sensitivity of neurones in slices of the rat spinal cord.
AB  - 1. The inherent temperature sensitivity of 343 spontaneously active neurones
      recorded from rat spinal cord (SC) slices was investigated
      electrophysiologically. Recordings were made from 321 neurons from transverse and
      22 neurons from longitudinal slices and their thermosensitivity was determined by
      relating changes in firing rate to changes in slice temperature. 2. Of the
      neurones from transverse slices, 53% were warm sensitive, 2% were cold sensitive
      and 45% were temperature insensitive. In longitudinal slices, 68% were warm
      sensitive and the remaining neurones were temperature insensitive. 3. When
      classified according to their recording sites in transverse slices, warm
      sensitive neurones in laminae I and II had the same mean temperature coefficient
      compared with those recorded from lamina X, despite the fact that the latter had
      a significantly higher spontaneous activity. 4. The intrinsic temperature
      sensitivity of the majority of warm-sensitive neurones was confirmed by blocking
      their synaptic input. 5. A transient overshoot in activity, i.e. a dynamic
      response characteristic following rapid temperature stimuli (0.4 degree C s-1)
      was observed in 73% of the warm-sensitive and 59% of the temperature-insensitive
      neurones in laminae I and II in response to rapid warming, but only rarely (<
      10%) in lamina X. 6. Temperature-sensitive SC neurones share response
      characteristics with temperature-sensitive neurones in the preoptic and anterior
      hypothalamic (PO/AH) area and with peripheral temperature receptors.
      Functionally, these neurones may represent the cellular basis for the temperature
      sensory function of the spinal cord that has been well characterized in vivo in
      homeothermic species.

PMID- 9032696
TI  - Evidence for uncoupling of oxygen and glucose utilization during neuronal
      activation in rat striatum.
AB  - 1. Changes in regional cerebral blood flow (rCBF), tissue oxygen and
      extracellular glucose were measured during neuronal activation, using implanted
      electrodes in the striatum of freely moving rats. 2. There was a parallel
      increase in rCBF and oxygen in response to neuronal activation. 3. During the
      neuronal activation there was a decrease in extracellular glucose; following
      neuronal activation there was a slow rise in extracellular glucose which took 30
      min to return to basal levels. 4. The implications of the different time courses
      of these changes are discussed.

PMID- 9032697
TI  - Developmental loss of hypoxic chemosensitivity in rat adrenomedullary chromaffin
      cells.
AB  - 1. We investigated whether adrenomedullary chromaffin cells (AMCs) derived from
      neonatal (postnatal day (P) 1-P2) and juvenile (P13-P20) rats, and maintained in
      short-term culture (1-3 days), express O2-chemoreceptive properties. 2. In whole
      cell recordings, the majority (approximately 70%; n = 47) of neonatal AMCs were
      sensitive to hypoxia. Under voltage clamp, acute hypoxia (PO2 approximately 40
      mmHg) suppressed voltage-dependent K+ current by 25.1 +/- 3.4% (mean +/- S.E.M.;
      n = 22); under current clamp, acute hypoxia caused a membrane depolarization of
      14.1 +/- 1.3 mV (n = 13) from a resting potential of -54.8 +/- 2.8 mV (n = 13),
      and this was often sufficient to trigger action potentials. 3. Exposure of
      neonatal AMC cultures to a moderate (PO2 approximately 75 mmHg) or severe (PO2
      approximately 35 mmHg) hypoxia for 1 h caused a dose-dependent stimulation
      (approximately 3 or 6 times normoxia, respectively) of catecholamine (CA)
      release, mainly adrenaline, determined by HPLC. This induced CA release was
      abolished by the L-type calcium channel blocker, nifedipine (10 microM). 4. In
      contrast to the above results in neonates, hypoxia had no significant effects on
      voltage-dependent K+ current, membrane potential, or CA release in juvenile AMCs.
      5. We conclude that rat adrenal chromaffin cells possess a developmentally
      regulated O2-sensing mechanism, similar to carotid body type I cells.

PMID- 9032698
TI  - Evaluation of purine nucleotide loss, lipid peroxidation and ultrastructural
      alterations in post-hypoxic hepatocytes.
AB  - 1. Hypoxic alterations in isolated rat hepatocytes were demonstrated by a 90% ATP
      loss during 60 min of ischaemia and temporary increases of nucleotide degradation
      products. 2. The oxidative stress during reoxygenation was demonstrated in these
      cells by a decrease in reduced glutathione (GSH) concentration (30%) and a
      threefold increase in lipid peroxidation products such as 4-hydroxynonenal and
      thiobarbituric acid-reactive substances (TBA-RSs). The tremendous GSH loss could
      not be balanced by the slight oxidized glutathione (GSSG) increase during
      reoxygenation. 3. For the first time the involvement of free radicals was
      directly demonstrated using electron spin resonance (ESR) spectroscopy in
      reoxygenated liver cells. Using the spin trap 5,5-dimethylpyrroline-1-oxide
      (DMPO), a carbon-centred radical and the adduct of the hydroxyl radical could be
      detected during early reoxygenation. 4. Morphological alteration of cells was
      observed, beginning during hypoxia and increasing during post-hypoxic
      reoxygenation. Electron microscopic findings of hypoxic and post-hypoxic cell
      damage included pyknosis of nuclei, spherical transformation of mitochondria and
      increased number of vesicles.

PMID- 9032700
TI  - Evidence for nitric oxide-mediated sympathetic forearm vasodiolatation in humans.
AB  - 1. Our aim was to determine if sympathetic vasodilatation occurs in the human
      forearm, and if the vasodilating substance nitric oxide contributes to this
      dilatation. We also sought to determine if the nitric oxide might be released as
      a result of cholinergic stimulation of the vascular endothelium. 2. Blood flow
      was measured in the resting non-dominant forearm with venous occlusion
      plethysmography. To increase sympathetic traffic to the resting forearm, rhythmic
      handgrip exercise to fatigue followed by post-exercise ischaemia was performed by
      the dominant forearm. A brachial artery catheter in the non-dominant arm was used
      to selectively infuse drugs. 3. During control conditions, there was mild
      vasodilatation in the resting forearm during exercise followed by constriction
      during post-exercise ischaemia. When exercise was performed after brachial artery
      administration of bretylium (to block noradrenaline release) and phentolamine (an
      alpha-adrenergic antagonist), profound vasodilatation was seen in the resting
      forearm during both exercise and post-exercise ischaemia. 4. When the nitric
      oxide synthase blocker NG-monomethyl-L-arginine (L-NMMA) was administered in the
      presence of bretylium and phentolamine prior to another bout of handgripping,
      little or no vasodilatation was seen either during exercise or post-exercise
      ischaemia. Atropine also blunted the vasodilator responses to exercise and post
      exercise ischaemia after bretylium and phentolamine. 5. These results support the
      existence of active sympathetic vasodilatation in the human forearm and the
      involvement of nitric oxide in this phenomenon. They also suggest nitric oxide
      might be released as a result of cholinergic stimulation of the vascular
      endothelium.

PMID- 9032699
TI  - Long-term influence of neonatal hypoxia on catecholamine activity in carotid
      bodies and brainstem cell groups of the rat.
AB  - 1. In order to determine the long-term influence of neonatal hypoxia on
      catecholaminergic activity in peripheral arterial chemoreceptors and brainstem
      noradrenergic cell groups (A1, A2, A5 and A6), 1-day-old male rat pups were
      subjected to hypoxia (10% oxygen) for 6 days and then supplied with normal air.
      Control animals were kept at normoxia from birth. Rats were killed at either 3 or
      8 weeks of age. 2. The content of dopamine and noradrenaline in carotid bodies of
      neonatally hypoxic rats was increased at both 3 and 8 weeks of age. 3.
      Noradrenaline turnover was selectively decreased in the caudal portion of A2
      (located in the area of chemosensory afferent projection) at 8 weeks of age (-76
      +/- 2%), while this turnover was unaffected in rostral A2 cells. Noradrenergic
      activity in A1, A5 and A6 was altered by neonatal hypoxia in an age-dependent
      fashion. 4. The data suggest that neonatal hypoxia induces long-term changes in
      the basal activity of the carotid body and brainstem noradrenergic cell groups.
      Such changes might contribute to neuronal regulation of the delayed respiratory,
      arousal and neural sequelae associated with neonatal hypoxia. These changes could
      also be involved in the early programming of respiratory and blood pressure
      control.

PMID- 9032701
TI  - The effect of passive tilting on microvascular parameters in the human calf: a
      strain gauge plethysmography study.
AB  - 1. Cumulative small steps in venous congestion pressure were used to study the
      effect of passive tilt on vascular parameters in dependent tissues. Using this
      protocol we have non-invasively assessed venous pressure (Pv,est), isovolumetric
      cuff pressure (Pv,i), which is the congestion cuff pressure (Pcuff) that has to
      be exceeded to induce fluid filtration. We have also assessed microvascular
      filtration capacity (Kf), which is the linear relationship between filtration
      rate (Jv) and Pcuff, when Pcuff > Pv,i, and is the product of the available
      exchange vessel surface area and wall conductance. 2. Subjects were passively
      tilted to increase the venous pressure at the level of the calf by 47.4 +/- 2.4
      mmHg (mean +/- S.E.M.). The value of Pv,i increased from 20.6 +/- 1.8 to 48.5 +/-
      3.8 mmHg after the imposition of the tilt. This change may reflect the increased
      colloid osmotic pressure at the microvascular interface that is known to occur in
      response to this manoeuvre. 3. The pre-tilt value of Kf did not change after the
      imposition of the passive tilt, the values being 3.2 +/- 0.4 x 10(-3) and 3.6 +/-
      0.4 x 10(-3) ml min-1 (100 ml-1) mmHg-1, respectively, (n = 13). 4. These results
      support the notion that passive postural change alters the pre-capillary
      resistance, thereby altering the pressure and flow characteristics within the
      exchange vessels, but does not alter the surface area available for fluid
      exchange in the calf, contrary to previous findings in the dependent human foot
      using a single-step venous occlusion protocol.

PMID- 9032702
TI  - Role of caloric content on gastric emptying in humans.
AB  - 1. This study examined the effects of caloric content (caloric density and the
      nature of calories) on the rate of gastric emptying using the double-sampling
      gastric aspiration technique. Four test meals of 600 ml (glucose, 0.1 kcal ml-1;
      pea and whey peptide hydrolysates, both 0.2 kcal ml-1; milk protein, 0.7 kcal ml
      1) were tested in six healthy subjects in random order on four separate
      occasions. 2. The glucose solution was emptied the fastest with a half-time of
      9.4 +/- 1.2 min (P < 0.05) and the milk protein the slowest with a half-time of
      26.4 +/- 10.0 min (P < 0.05); the pea peptide hydrolysate and whey peptide
      hydrolysate solutions had half-times of emptying of 16.3 +/- 5.4 and 17.2 +/- 6.1
      min, respectively. The rates of gastric emptying for the peptide hydrolysate
      solutions derived from different protein sources were not different. 3. Despite
      the lower rate of gastric emptying for the milk protein solution, the rate of
      caloric delivery to the duodenum during the early phase of the gastric emptying
      process was higher than that for the other three solutions (46.3 +/- 6, 63.5 +/-
      22, 62.5 +/- 19 and 113.8 +/- 25 cal min-1 kg-1 for the glucose, pea peptide
      hydrolysate, whey peptide hydrolysate and milk protein meals, respectively; P <
      0.05). The caloric density of the test solutions was linearly related to the half
      time of gastric emptying (r = 0.96, P < 0.05) as well as to the rate at which
      calories were delivered to the duodenum (r = 0.99, P < 0.001). 4. This study
      demonstrates that the rate of gastric emptying is a function of the caloric
      density of the ingested meal and that a linear relationship exists between these
      variables. Furthermore, the nature of the calories seems to play a minor role in
      determining the rate of gastric emptying in humans.

PMID- 9032703
TI  - Dr. Richard Mayou interviews Dr. Geoffrey Lloyd, editor 1986-1993.

PMID- 9032704
TI  - Physical symptoms and depressive disorders in childhood and adolescence.

PMID- 9032705
TI  - Statistical power and implications of meta-analysis for clinical research in
      psychosocial oncology.

PMID- 9032706
TI  - Fatigue in the chronic fatigue syndrome: a cognitive phenomenon?
AB  - What is the source of the perception of excessive fatigue in the chronic fatigue
      syndrome (CFS)? Studies of physiological response to aerobic activity, of muscle
      pathology and muscle function in CFS, are reviewed, and suggest that the
      subjective report of fatigue is not due to any peripheral impairment. In
      addition, current technological methods such as electroencephalography have
      failed to uncover the nature of any abnormality in the central motor unit. A
      physiological model which proposes that patients with CFS possess a reduced
      threshold for sensory fatigue signals is rejected, because it fails to account
      for recent findings. Instead, it is suggested that the perception of fatigue in
      CFS is enhanced by idiosyncrasies in cognitive processing. The implications of
      this view to our understanding of the perpetuation of CFS as a whole are
      explored.

PMID- 9032707
TI  - In-patient psychiatric referrals in a teaching hospital: a case controlled
      report.
AB  - The 77 (47 females, 30 males) in-patient referrals to the Psychiatric Department
      of the University College Hospital, Ibadan, Nigeria, over a 1-year period, were
      compared with a control sample of 75 (45 females, 30 males) unreferred patients.
      The low referral rate of 0.8%, after excluding deliberate self-harm (relatively
      infrequent in Nigeria), was comparable to reports in Western literature.
      Treatable minor psychiatric morbidity, mainly anxiety and depressive disorders,
      occurred in 41.3% of the controls. Sixty-eight percent of those referred had
      definite mental disorders, most commonly psychoses (50.7%), especially delirium
      (29.9%). Infectious disorders, notably Salmonella typhi infection, were the most
      predominant physical etiological factors. The results are discussed and the
      implications highlighted.

PMID- 9032708
TI  - The low specificity of the Hyperventilation Provocation Test.
AB  - The Hyperventilation Provocation Test (HVPT) has become a routine procedure in
      the diagnosis of hyperventilation syndrome (HVS). During an HVPT the patient
      voluntarily overbreathes for several minutes to produce hypocapnia. The test is
      considered positive if the induced symptoms are recognized by the patient as
      similar to those experienced in daily life. The present study tests the
      assumption that hypocapnia is the primary trigger for symptoms during an HVPT. In
      a randomized double-blind crossover design. 115 patients suspected of HVS and 40
      healthy controls performed an HVPT and a placebo test (PT, isocapnic
      overbreathing). The HVPT induced more symptoms than the PT, especially more
      neuromuscular symptoms, cerebral symptoms, paresthesias, and temperature
      sensations. However, the absolute difference between the number of symptoms
      induced by the HVPT and PT was small. In patients, the PT induced 66% of symptoms
      induced by the HVPT. In the control group this percentage was 60%. The low
      specificity of the HVPT implies that symptom recognition during the HVPT is
      invalid as a diagnostic criterion for HVS.

PMID- 9032709
TI  - The ECLW Collaborative Study: III. Training and reliability of ICD-10 psychiatric
      diagnoses in the general hospital setting--an investigation of 220 consultants
      from 14 European countries. European Consultation Liaison Workgroup.
AB  - A comprehensive training program for reliable use of the ICD/10 in Consultation
      Liaison (C-L) psychiatry was conducted with 220 psychiatrists and psychologists
      from 14 European countries. The training included rating of written test cases
      and development of a coding manual to avoid diagnostic pitfalls not addressed in
      the ICD-10 manual. Following this training, all consultants rated 13 written case
      histories. One hundred sixty-seven consultants (76%) had a kappa (kappa) of at
      least 0.70. Only 13 (6%) had a kappa 0.40. The percentage of high reliability
      raters was evenly distributed among the different countries. Consultants had some
      problems in the differentiation between adjustment disorders and depressive
      disorders, and in the classification of disorders where ICD-10 differs from the
      DSM-III-R system. National biases in diagnostic practice were found with regard
      to the "case" concept and the role of alcohol in confusional states. Finnish
      consultants coded "no psychiatric disorder" significantly more often, whereas
      German and Italian consultants attributed delirious state more often to alcohol
      than consultants from other European countries. The study demonstrates that it is
      possible to achieve acceptable interrater reliability in applying the ICD-10
      guidelines, through training programs designed for C-L psychiatrists and
      psychologists. Nevertheless, this first cross-national study shows the importance
      of addressing differences in national diagnostic practice.

PMID- 9032710
TI  - Long-term symptom patterns in duodenal ulcer: psychosocial factors.
AB  - Seventy-five patients with recent-onset dyspepsia and endoscopically visible
      duodenal ulcer underwent psychological evaluation. Following ranitidine
      treatment, they were reinterviewed periodically for 12 to 76 months (mean 38.6).
      Ulcer symptoms were present during a mean of 14.9% of follow-up months. Patients
      did significantly worse if they had a low-status occupation, low education,
      depression, stressful life events, or abnormal Minnesota Multiphasic Personality
      Inventory at baseline. Of patients recalling premorbid life stress, those with a
      normal MMPI had a particularly benign course, whereas those with an abnormal MMPI
      did particularly poorly (6% versus 29% of months symptomatic: p < 0.04). Age,
      gender, smoking, drinking, antiinflammatory drugs, pepsinogen, Helicobacter
      pylori titers, and initial healing had no prognostic effect. Low socioeconomic
      status, life stress, depression, and psychopathology each predict a relatively
      poor symptom outcome for duodenal ulcer treated with antisecretory therapy, but
      psychologically stable individuals who develop an ulcer under stress have an
      excellent long-term prognosis.

PMID- 9032711
TI  - Referral of Asian patients to a GI clinic.
AB  - This study compared gastrointestinal (GI) symptoms and psychiatric morbidity in
      consecutive new out-patients presenting to a district general hospital. In a 6
      month period 36 patients of South Asian origin were referred to the clinic. They
      were compared in terms of GI symptoms and psychiatric morbidity with white
      European controls, both with a large sample of clinic attenders, and with a
      subsample of 36 matched for age, gender, and diagnosis. A total of 72% (26 of 36)
      of Asian patients had functional GI disorders compared to 48% (42 of 88) of white
      patients (p < 0.05). However, comparisons of matched patients showed that Asian
      patients with functional GI disorders had less severe GI symptoms than the
      matched white patients, and fewer had psychiatric disorder (23% of Asians and 42%
      of white Europeans). These results suggest that the threshold for referral for
      Asian patients with functional GI disorders to hospital clinics is lower than for
      white patients. Detection and management of somatization in Asian patients in
      primary care need to be improved, and referral patterns of general practitioners
      need to be explored in future research.

PMID- 9032713
TI  - Alexithymia--a useful concept for all psychiatrists?

PMID- 9032712
TI  - Influence of breathing therapy on complaints, anxiety and breathing pattern in
      patients with hyperventilation syndrome and anxiety disorders.
AB  - The effect of breathing therapy was evaluated in patients with hyperventilation
      syndrome (HVS). The diagnosis of HVS was based on the presence of several
      suggestive complaints occurring in the context of stress, and reproduced by
      voluntary hyperventilation. Organic diseases as a cause of the symptoms were
      excluded. Most of these patients met the criteria for an anxiety disorder. The
      therapy was conducted in the following sequence: (1) brief, voluntary
      hyperventilation to reproduce the complaints in daily life: (2) reattribution of
      the cause of the symptoms to hyperventilation: (3) explaining the rationale of
      therapy-reduction of hyperventilation by acquiring an abdominal breathing
      pattern, with slowing down of expiration: and (4) breathing retraining for 2 to 3
      months by a physiotherapist. After breathing therapy, the sum scores of the
      Nijmegen Questionnaire were markedly reduced. Improvements were registered in 10
      of the 16 complaints of the questionnaire. The level of anxiety evaluated by
      means of the State-Trait Anxiety Inventory (STAI) decreased slightly. The
      breathing pattern was modified significantly after breathing retraining. Mean
      values of inspiration and expiration time and tidal volume increased, but end
      tidal CO2 concentration (FETCO2) was not significantly modified except in the
      group of younger women (< or = 28 years). A canonical correlation analysis
      relating the changes of the various complaints to the modifications of breathing
      variables showed that the improvement of the complaints was correlated mainly
      with the slowing down of breathing frequency. The favorable influence of
      breathing retraining on complaints thus appeared to be a consequence of its
      influence primarily on breathing frequency, rather than on FETCO2.

PMID- 9032714
TI  - How are alexithymia and physical illness linked? A review and critique of
      pathways.
AB  - We review the empirical literature and critique four possible pathways linking
      alexithymia and physical illness; (a) alexithymia leads to organic disease
      through physiological or behavioral mechanisms: (b) alexithymia leads to illness
      behavior (physical symptoms, disability, excessive health care use) through
      cognitive or social mechanisms: (c) physical illness leads to alexithymia; and
      (d) both alexithymia and physical illness result from sociocultural or biological
      factors. Our review suggests that alexithymia is associated with tonic
      physiological hyperarousal, certain types of unhealthy behavior, and a biased
      perception and reporting of somatic sensations and symptoms. Alexithymia also
      appears to influence health care use, but in a complex fashion. Although trauma
      may give rise to alexithymia, whether physical illness such as chronic pain does
      so is not known, and there is little evidence that sociocultural or biological
      factors lead to both alexithymia and physical illness. We conclude that
      alexithymia probably influences illness behavior, but there is little support for
      the hypothesis that alexithymia leads to chronic organic disease, especially when
      one distinguishes organic disease from illness behavior.

PMID- 9032715
TI  - Alexithymia, social support and health problems.
AB  - This article presents three studies examining whether alexithymia is associated
      with less perceived and network social support, whether such relationships are
      accounted for by reduced social skills associated with alexithymia, and whether
      limited social support links alexithymia to health problems. The relationships
      between alexithymia (Toronto Alexithymia Scale), social variables, and physical
      health and depression were examined in both healthy young adults and patients.
      Alexithymia (especially deficits in identifying and communicating feelings) was
      related to less perceived support, fewer close relationships, and less social
      skill: the social skills deficit accounted fully for the association between
      alexithymia and a smaller social network. Additionally, alexithymia was related
      to both somatic complaints and depression, but social support generally was not.
      It is concluded that alexithymia is associated with reduced perceived and network
      social support, that these associations are likely due to alexithymia-related
      deficiencies in social skills but that reduced social support does not account
      for the relationship between alexithymia and health problems.

PMID- 9032716
TI  - Ethnolinguistic correlates of alexithymia: toward a cultural perspective.
AB  - Gender and ethnolinguistic correlates of alexithymia were explored by having a
      large, ethnically heterogeneous sample of university students in Toronto, Canada,
      complete the 20-item Toronto Alexithymia Scale (TAS-20). Men scored higher in the
      externally oriented thinking factor than women. Non-native English speakers
      scored higher on the overall TAS-20, as well as on the difficulty identifying
      feelings factor, than native English speakers. Further analyses showed that
      native Chinese language speakers scored consistently higher than native English
      and native European language speakers on the overall TAS-20 and its three
      underlying factors. These ethnolinguistic differences may reflect sociocultural
      influences making ethnic Chinese individuals likely to be less psychologically
      minded and more somatically oriented vis-a-vis their emotions than those from
      Western, ethnocultural traditions. Whether alexithymia should be construed as an
      "etic" construct (i.e., widely applicable across many different cultures) or an
      "emic" one (i.e., applicable to only one or two cultures) is discussed.

PMID- 9032717
TI  - Alexithymia and risk of death in middle-aged men.
AB  - We prospectively examined the association between alexithymia and risk of death
      over an average follow-up time of nearly 5.5 years in 42- to 60-year-old men (N =
      2297) participating in the Kuopio Ischemic Heart Disease Risk Factor Study
      (KIHD). Alexithymia, impairment in identification, processing, and verbal
      expression of inner feelings, was assessed by the validated Toronto Alexithymia
      Scale (TAS) In age-adjusted survival analyses, men in the highest alexithymia
      quintile had a twofold greater risk of all-cause death (p < 0.001) and a
      threefold greater risk of death from accidents, injury, or violence (p < 0.02)
      relative to the men in the three lowest alexithymia quintiles. There was little
      evidence for confounding by behavioral factors (smoking, alcohol consumption,
      physical activity). physiological risk factors (LDL, HDL, body mass index,
      hypertension), socioeconomic status, marital status, perceived health, prior
      diseases and diagnoses, depressive symptoms or social connections. Consistent and
      even stronger associations between alexithymia and all-cause death were found in
      a healthy subgroup (N = 1650). Why difficulties in dealing with emotions
      associate with increased mortality remains unclear. Our findings suggest that the
      association is independent from the effect of well-known behavioral, biological,
      and psychosocial risk factors.

PMID- 9032718
TI  - Cross validation of the factor structure of the 20-item Toronto Alexithymia
      Scale: an Italian multicenter study.
AB  - The 20-item Toronto Alexithymia Scale (TAS-20) has been shown in previous
      research to measure a general dimension of alexithymia with three intercorrelated
      factors. This study evaluated the reliability and factorial validity of an
      Italian translation of the TAS-20 in a group of normal adults (N = 206) and in a
      mixed group of medical and psychiatric outpatients (N = 642). Using confirmatory
      factor analyses, the previously established three-factor model of the TAS-20 was
      found to be replicable in both groups. In addition, the Italian TAS-20
      demonstrated adequate estimates of internal reliability and test-retest
      reliability. Although evaluation of the convergent, discriminant, and concurrent
      validity of the TAS-20 is required in Italian populations, the present results
      support the use of the Italian translation of the scale for clinical and research
      purposes.

PMID- 9032719
TI  - Relationships between alexithymia and psychological characteristics associated
      with eating disorders.
AB  - This study examines the relationships between alexithymia and psychological
      characteristics and behaviors that are commonly associated with eating disorders.
      The 20-item Toronto Alexithymia Scale (TAS-20) and the Eating Disorder Inventory
      (EDI) were administered to a group of 48 female patients with anorexia nervosa, a
      matched comparison group of 30 normal women, and an unmatched comparison group of
      116 male and 118 female university students. In the anorexic and male student
      groups, the TAS-20 correlated significantly and positively with the EDI
      subscales, Ineffectiveness, Interpersonal Distrust, Interoceptive Awareness, and
      Maturity Fears. The TAS-20 correlated significantly only with Interpersonal
      Distrust in the matched comparison group, and only with Ineffectiveness and
      Interpersonal Distrust in the female student group. The results suggest that
      alexithymia is related to several psychological traits that are characteristic of
      patients with eating disorders and thought to play a role in the development of
      the disorders but is unrelated to attitudes and behaviors concerning abnormal
      eating and body weight and shape.

PMID- 9032720
TI  - A longitudinal study of alexithymia and psychological distress in inflammatory
      bowel disease.
AB  - A group of 104 patients with inflammatory bowel disease (IBD) was followed
      longitudinally for 6 months. While anxiety and depression scores were influenced
      over time by changes in the level of disease activity, there was no significant
      change in alexithymia scores. The findings support the contention that
      alexithymia is a stable personality characteristic in some IBD patients, in
      contrast to anxiety and depression which are state phenomena influenced by the
      level of disease activity.

PMID- 9032721
TI  - Alexithymia, defensiveness and cardiovascular reactivity to stress.
AB  - This article attempts to further our understanding of alexithymia by testing two
      conceptual questions about the construct: (a) Is alexithymia characterized by
      reduced autonomic activity? and (b) Can it be clearly distinguished from
      defensiveness? Eighty healthy university students completed a battery of
      personality scales including the Toronto Alexithymia Scale, measures of self
      deception and impression management, depression, and anger-in. They also
      participated in three lab stress tasks: isometric handgrip; mental arithmetic;
      and a negative affect provocation task. Blood pressure and heart rate were
      monitored throughout the lab procedure. Analyses were conducted with tercile
      groups of low, medium, and high alexithymia scorers. The "high alexithymia"
      tercile showed smaller heart rate responses to the stress tasks and more anger-in
      behavior. Blood pressure responses did not differentiate the low/ medium/high
      alexithymia subgroups. Alexithymia scores were unrelated to defensiveness, that
      is, there was no relationship between alexithymia and impression management or
      self-deception, and alexithymia was unrelated to depression. We conclude that
      students defined as "high alexithymia" on the Toronto Alexithymia Scale are not
      self-deceptive nor do they try to leave a particular impression; they tend to be
      somewhat hypoaroused autonomically, and they report as many psychological
      distress symptoms as do subjects with lower TAS scores.

PMID- 9032722
TI  - Childhood abuse, alexithymia and personality disorder.
AB  - I examined the relationships among childhood abuse, alexithymia, and personality
      disorder. Participants were 60 adults who were receiving outpatient
      psychotherapy. Both the participants and their therapists used the Toronto
      Alexithymia Scale to provide independently information concerning the client's
      level of alexithymia. The therapists provided information concerning DSM-III-R
      personality disorder diagnoses, and participants completed portions of the
      Personality Diagnostic Questionnaire-Revised. Information concerning childhood
      abuse history was obtained from the therapists. As expected, childhood abuse,
      alexithymia, and personality disorder were all associated with each other. The
      abilities to identify and communicate emotions were differentially associated
      with childhood abuse and personality disorder.

PMID- 9032723
TI  - A California Q-set alexithymia prototype and its relationship to ego-control and
      ego-resiliency.
AB  - The primary purposes of the present study were to use the Q-sort method to
      develop a measure of alexithymia and to locate the construct within a two
      dimensional (ego-control and ego-resiliency) model of personality. Thirteen
      professional judges described the characteristics of the alexithymic personality
      with the 100-item California Q-set. Scores from the sorts were aggregated to form
      the Alexithymia Prototype, which had a Spearman-Brown reliability of 0.99.
      Alexithymic people were described as having difficulties experiencing and
      expressing emotion, lacking imagination, and being literal, socially conforming,
      and utilitarian; they lack insight, are humorless, and experience
      meaninglessness; and anxiety and tension find outlet in bodily symptoms. This
      description is consistent, for the most part, with modern formulations of the
      alexithymia construct. In the language of the two-dimensional personality model,
      alexithymic individuals appear to be overcontrolling and lacking ego-resiliency
      (i.e., constricted, anxious, rigid, and withdrawn). We, therefore, compared the
      Alexithymia Prototype with two independently developed prototypes, Overcontrol
      and Ego-Resiliency. The Q-correlations between alexithymia and overcontrol and
      between alexithymia and ego-resiliency were 0.45 and -0.70, respectively.
      Although item analyses confirmed moderate overlap between alexithymia and
      overcontrol and considerable overlap between alexithymia and lacking ego
      resiliency (ego-brittle), item differences suggest that alexithymia, indeed, is a
      unique personality construct.

PMID- 9032740
TI  - Menopausal experiences of Thai women. Part 1: Symptoms and their correlates.
AB  - This study was a cross-sectional survey of mid-aged Thai women with the following
      aims: to describe their experience of symptoms and attitudes to menopause and to
      examine the relationships between symptoms, attitudes to menopause,
      sociodemographic variables and menopausal status. The sample was 268 women aged
      between 40 and 59 y who had accompanied patients to the outpatients department of
      the Royal Irrigation Hospital. Mean age at menopause was 50.13 (SD 4.67) y. Fifty
      one percent were premenopausal. 9% perimenopausal and 40% postmenopausal. The
      symptoms which showed strongest associations (P < 0.001) with menopausal status
      were: joint aches/pain, hot flushes, depression and insomnia. Women most likely
      to experience symptoms were: older than 50 years of age, had more children, peri-
      or post-menopausal, of little education, housewives or landowners and reported
      their health was not so good and required treatment.

PMID- 9032741
TI  - Menopausal experiences of Thai women. Part 2: The cultural context.
AB  - This paper describes the cultural context of middle-aged Thai women who took part
      in a survey of symptoms and attitudes to menopause. The women lived in Nonthaburi
      province, adjacent to Bangkok, which has undergone a transition from rural to
      urban. Household structure often includes three generations. There have been
      changing opportunities for women in areas of education, occupation and family
      size and women's power increases with age. Thai women perceive menstruation as an
      indicator of health and take special care during menstruation. There is a special
      idiom in Thai 'leod cha pai-lom cha ma' (the blood will go--the wind will come)
      used to describe changes in a woman's behaviour, emotions and well-being during
      the menopause. These changes are expected to happen occasionally, not in every
      woman. Some women looked forward to menopause, while others were found to be
      ambivalent towards it.

PMID- 9032743
TI  - Alcohol consumption and age of maternal menopause are associated with menopause
      onset.
AB  - OBJECTIVES: To examine whether a number of nutritional and familial factors were
      associated with menopausal development. METHODS: A prospective postal survey
      amongst a random sample of 1227 women aged 47 to 51 who were premenopausal in a
      cross-sectional survey 2 years previously. Women were classed into three groups;
      premenopause (regular menstruation); irregular menstruation; postmenopausal
      (absence of menstrual cycle for at least 6 months). Proportional odds regression
      was used to identify those factors which were independently predictive of
      subsequent menopausal development. RESULTS: There was an 80% (n = 983) survey
      response rate. After exclusion of current HRT users (n = 178); 150 (19%) women
      were postmenopausal, 277 (34%) had erratic menstruation and 378 (47%) were
      premenopause. There were significant univariate associations between menopausal
      status and age (P < 0.001), age of maternal menopause (P = 0.006), alcohol
      consumption (P = 0.005) and social class (P = 0.03). Maternal age and alcohol
      consumption were significantly correlated with estradiol levels (r = 0.45, P =
      0.02, and r = 0.61, P = 0.02 for maternal age and alcohol consumption,
      respectively). In proportional odds regression analyses, age, maternal menopausal
      age, alcohol consumption and smoking were independently associated with
      menopausal status. CONCLUSIONS: These results suggest that, (1) there is a strong
      familial association in menopausal age, and (2) moderate consumption of alcohol
      is associated with delayed menopausal development.

PMID- 9032742
TI  - Effect on sexual life--a comparison between tibolone and a continuous estradiol
      norethisterone acetate regimen.
AB  - OBJECTIVES: to compare the effects of tibolone 2.5 mg (Livial) with those of 17
      beta-estradiol 2 mg plus norethisterone acetate 1 mg (Kliogest) on sexual life.
      METHODS: in a 48 week, double blind, multicenter study, 437 postmenopausal women
      were randomised to treatment with either tibolone or 17 beta-estradiol 2 mg plus
      norethisterone acetate. Treatment groups were compared with respect to different
      aspects of sexual life with a questionnaire covering sexual experience and
      responsiveness during the last 30 days. RESULTS: a total of 315 subjects
      completed 48 weeks treatment. In the E2/NETA group an improvement after 48 weeks
      compared to baseline was observed in five out of seven items assessing sexual
      life. In the tibolone group an improvement regarding all seven items assessing
      sexual life was seen. When tibolone was compared to E2/NETA significantly higher
      scores were found for the items assessing 'frequency', 'satisfaction' and
      'enjoyment'. CONCLUSIONS: this study indicate that tibolone and E2/NETA -which
      both have an androgenic profile-affect several aspects of sexual life positively.
      The difference with respect to satisfaction with sexual enjoyment and frequency
      could be of clinical importance.

PMID- 9032744
TI  - Estradiol delivery by vaginal rings: potential for hormone replacement therapy.
AB  - OBJECTIVES: To determine if delivery of estradiol from elastomeric vaginal rings
      gives estradiol blood levels in the range associated with effective estrogen
      replacement therapy and to determine the relation between in vitro estradiol
      release from the rings and blood levels in vivo. Secondary objectives related to
      changes in lipoprotein cholesterol, changes in climacteric symptoms, and
      evaluation of acceptability to users. METHODS: Three ring variants releasing
      approximately 100, 150 and 200 micrograms/day of estradiol in vitro were used
      through 22 days in 21 postmenopausal women, 7 on each dose levels. Blood samples
      for measurement of estradiol were taken at 3-4 day intervals. Lipoprotein
      cholesterol was measured before and at the end of treatment. Women were
      questioned about climacteric symptoms and about their satisfaction with the ring.
      RESULTS: Mean serum estradiol levels for the three groups of rings were 63 +/- 6,
      94 +/- 5 and 136 +/- 13 pg/ml for the 100, 150 and 200 micrograms/day rings,
      respectively. FSH levels declined during ring use and the maturation values of
      cells collected on vaginal swabs markedly increased. Total and LDL cholesterol
      were significantly reduced and HDL cholesterol was not significantly changed. All
      women reported relief of postmenopausal symptoms. Vaginal discomfort during the
      first 3 days of use was reported by 12 women but overall satisfaction with the
      method was high. CONCLUSIONS: Women using the vaginal rings attained estradiol
      blood levels compatible with control of climacteric symptoms and bone loss. The
      relation between in vitro estradiol release and blood levels in vivo was
      essentially identical for all 3 doses. The use of vaginal rings to deliver
      estradiol for hormone replacement therapy is judged to merit further evaluation.

PMID- 9032745
TI  - Perimenopausal bone density screening--will it help prevent osteoporosis?
AB  - OBJECTIVE: To estimate the potential efficacy and cost-effectiveness of hormone
      replacement therapy (HRT) in the prevention of osteoporotic fractures, with and
      without the assistance of perimenopausal bone mineral density (BMD) screening.
      METHOD: Residual lifetime fracture experience of a hypothetical cohort of
      100,000. British women aged 45 years at baseline, modelled using prevailing UK
      mortality and fracture rates. Appropriate fracture risk gradients were used to
      estimate the distribution of future fragility fractures (distal forearm, proximal
      femur and clinically diagnosed vertebral fractures) according to quarters of
      baseline bone density measured at fracture specific sites. We assumed that 72% of
      the population could be contacted and would attend for HRT counselling, with or
      without bone densitometry, that 10 years of continuous HRT use would reduce
      fracture rates by 50%, and that compliance with HRT might vary between 10% and
      50%. Universal recommendation of HRT was compared to selective treatment
      protocols offering HRT to those women whose BMD fell below the 25th, 50th or 75th
      percentile of BMD at the lumbar spine, femoral neck or distal forearm, measured
      either singly or in combination. RESULTS: The proportion of future fractures
      averted was closely related to compliance with therapy, but for any given level
      of compliance, universal treatment always achieved the greatest reduction in
      fractures. If compliance was 10% universal HRT was also the most cost-effective
      strategy, but if compliance was higher or if the unit cost of HRT increased,
      selective strategies were often more cost-effective. The sensitivity of BMD
      screening in identifying women at risk of future fracture could be increased by
      relaxing the BMD decision threshold, or expanding the number of skeletal sites
      measured, or both. However increments in test sensitivity were always accompanied
      by reductions in specificity. CONCLUSIONS: If BMD measurement does not influence
      compliance, then universal treatment with HRT is likely to prevent more
      fractures, at a similar or lower average cost per fracture averted, than
      selective therapy. However, if BMD screening leads to increased compliance, or if
      more expensive forms of treatment were used, then our model suggests a favourable
      impact of screening on the numbers and/or net cost of fractures prevented.

PMID- 9032746
TI  - Effects of hormone deficiency, androgen therapy and calcium supplementation on
      bone mineral density in female transsexuals.
AB  - A total of 79 healthy female transsexuals, divided into four groups, were
      involved in this study. Group 1 comprised 15 pre-operated normal cycling females;
      Group 2, five pre-operated females who were on regular androgen therapy for 1-3
      years; Group 3, 27 post-operated females who were on regular androgen therapy for
      2-12 years; and Group 4, 32 post-operated females who either had stopped or were
      on irregular androgen therapy. A bone scan of the lumber spine, at positions L2
      L4, was carried out for each subject. A blood sample was taken for measurement of
      plasma testosterone concentrations. Ten subjects from Group 3 had a repeat bone
      scan following 10-39 months of calcium supplement (625 mg daily as calcium
      carbonate); another 10 post-operated females of Group 3 had a repeat bone scan 6
      59 months later; and five subjects from Group 4 had a repeat scan following
      resumption of regular androgen therapy for 17-27 months. The mean +/- SE
      concentrations of testosterone of Groups 1-4 were, respectively, 0.58 +/- 0.05,
      10.1 +/- 2.48, 7.7 +/- 0.98 and 0.99 +/- 0.14 ng/ml. Pre-operated females (Group
      2) following 1-3 years of regular androgen therapy had significantly higher BMD
      and age-matched BMD than corresponding levels in pre-operated normal cycling
      females in Group 1. While the age-matched BMDs of post-operated females, who were
      on regular androgen therapy, were not significantly different, the mean BMD was
      significantly lower than corresponding values in the controls of Group 1. Post
      operated females in Group 4 had significantly lower BMDs and age-matched BMDs as
      compared to corresponding values in controls of Group 1. The BMDs and age-matched
      BMDs of post-operated females, who were on regular androgen therapy, were
      significantly raised following daily calcium supplementation for durations
      ranging from 10-39 months. A repeat bone scan carried out following a lapse of 6
      59 months did not reveal any significant change in the BMDs and age-matched BMDs
      of 10 post-operated females on regular androgen therapy. On the other hand, the
      BMDs and age-matched BMDs of post-operated females in Group 4 were significantly
      raised following the resumption of regular androgen therapy for 17-27 months.
      Results of the present study showed that ovariectomy and remaining in the hormone
      deficient state for a sufficiently long duration was associated with a definite
      loss of bone mass. However, it was shown in this study that the resumption of
      regular androgen therapy for a sufficient duration could arrest this loss and,
      additionally, substantially increase the bone mass. Androgen appears to have a
      potentially greater impact on bone mass than oestrogen. Furthermore, calcium
      supplementation in a Singaporean population, which is accustomed to a low dietary
      calcium intake, can assist in the accretion of a higher bone mass in an adult
      population.

PMID- 9032747
TI  - A preliminary study on the effect of hormone replacement therapy on peripheral
      flow velocity in postmenopausal women.
AB  - Apart from predisposing to the formation of atherosclerosis in the coronary and
      cerebrovascular circulation, the menopause is also associated with an increased
      risk of developing peripheral vascular disease. The aim of this observational
      study was to determine whether the administration of hormone replacement therapy
      (HRT) had any effect on peripheral flow velocity in postmenopausal women. Changes
      in peripheral resistance were recorded in 11 healthy postmenopausal women using
      Doppler ultrasound. The pulsatility index (PI) of the brachial, radial, dorsalis
      pedis and popliteal arteries was measured before treatment and every 2 months
      after the commencement of HRT for 6 months. There was a significant decrease in
      the PI of the radial and dorsalis pedis arteries after HRT, and there were also
      reductions in the PI of the brachial and popliteal arteries which were not
      statistically significant. These changes persisted over the complete study
      period. Our findings suggest that the administration of HRT will have a
      beneficial effect on peripheral flow velocity in postmenopausal woman. These
      changes require confirmation in a larger controlled trial.

PMID- 9032748
TI  - Vaginal ultrasound of the endometrium in postmenopausal women with symptoms of
      urogenital atrophy on low-dose estrogen or tibolone treatment: a comparison.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy of locally
      administered low-dose estrogens (0.625 mg of conjugated estrogens) and orally
      administered tibolone in postmenopausal women with symptoms and signs of atrophic
      vaginitis. Vaginal ultrasound was performed for the evaluation of endometrial or
      ovarian abnormalities. METHODS: A 6-month comparative randomised prospective
      study of women taking tibolone and locally administered low-dose estrogens.
      Seventy two postmenopausal women with symptoms of atrophic vaginitis were
      examined with vaginal ultrasound. The endometrial thickness, the endometrial
      volume, the uterus and the ovaries were measured before and after 6 months of
      treatment with low-dose estrogens or tibolone. RESULTS: In group A (low-dose
      estrogens treatment) the mean endometrial thickness, before and after treatment,
      was 3.0 +/- 0.1 mm and 2.9 +/- 0.8 mm, respectively. The mean ovarian volume was
      3.9 ml. There were no changes in uterine volume during the treatment period. In
      group B (treated with tibolone) endometrial thickness was 3.2 +/- 0.3 mm and 3.2
      +/- 0.7 mm, respectively. One women experienced vaginal bleeding. The volume of
      corpus uteri was unchanged after treatment. The volume of both ovaries was 4.2 ml
      and 3.9 ml, respectively. The overall acceptability of both types of
      administration was good. CONCLUSIONS: This study, using vaginal ultrasound, has
      shown that either hormone replacement therapy with tibolone or symptomatic
      treatment with low-dose estrogens, gives no sign of endometrial proliferation
      measured as endometrial thickness.

PMID- 9032750
TI  - Mitogenic activity but not phenotype expression of rat osteoprogenitor cells in
      response to IGF-I is impaired in aged rats.
AB  - The age-related deficit in the dose response of osteoprogenitor cells to IGF-I
      was further investigated. As expected, the effective dose, but not the maximal
      effect, was shifted two orders of magnitude higher in old cells. In this paper,
      we examined whether this age-deficit can be attributed to an alteration in the
      expression and binding kinetics of IGF-I receptor. We showed that the levels of
      IGF-I receptor mRNA in cells, estimated by RT-PCR, were not significantly altered
      with age. Scatchard analysis showed that there were no significant differences in
      Kd and Bmax in cells from the two age groups. In a parallel study, we also showed
      that the expression of osteoblast phenotype markers was stimulated by IGF-I.
      However, no apparent differences in dose response curve were observed between two
      age groups. These results suggest that defect(s) in cell proliferation in aging
      may occur specifically in the signal transduction pathway between the receptor
      and the mitogenic response but not in the pathway associated with phenotype
      expression.

PMID- 9032749
TI  - Increase in cytokine production (IL-1 beta, IL-6, TNF-alpha but not IFN-gamma, GM
      CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis.
AB  - Postmenopausal osteoporosis is a progressive disorder characterized by a
      decreased bone mass and increased susceptibility to fractures. Several
      investigations have suggested that one of the mechanisms through which estrogen
      prevents bone loss was a modulation on secretion or release of various cytokines
      that are known to influence bone remodeling, even if some recent data have
      challenged this hypothesis. However, in established osteoporosis, the possibility
      that enhanced cytokines activity may account for the progression of this disease
      remains unclear and controversial. We sought here to determine whether production
      of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, GM-CSF and LIF, after direct
      stimulation in whole blood, was different in healthy (n = 30) or osteoporotic
      postmenopausal women (n = 24) and whether lumbar bone density (1-BMD) correlated
      with the values of cytokine production observed in these conditions. A
      significant difference was observed between the osteoporotic and control subjects
      for IL-1 beta (p < 0.0001), IL-6 (p < 0.001) and TNF-alpha (p = 0.027)
      productions, the values being higher in the osteoporotic women. No significant
      differences between the groups were observed for IFN-gamma (p = 0.51), GM-CSF (p
      = 0.70) or LIF (p = 0.97). In the whole population, statistically significant
      negative correlations were observed between lumbar BMD and IL-1 beta (r = -0.46)
      (p < 0.0005), IL-6 (r = -0.50) (p < 0.0001) and TNF-alpha (r = -0.39) (p < 0.005)
      production while no such correlations were observed for IFN-gamma, GM-CSF or LIF.
      In conclusion, the study of cytokine production by immune cells cultured in
      autologous whole blood suggests that in women more than 10 years past the
      menopause and presenting a decrease in lumbar bone density corresponding to the
      new WHO definition of "osteoporosis', production of IL-1 beta, IL-6 and TNF-alpha
      is still increased compared to controls matched for age and ovarian function,
      while no differences are reported for IFN-gamma, GM-CSF or LIF production.

PMID- 9032751
TI  - Kinetic constants of alpha-methyl-D-glucoside transport in the chick small
      intestine during perinatal development.
AB  - The kinetic parameters of alpha-methyl-D-glucoside (alpha Glc1Me) have been
      determined in the small intestine in order to establish developmental and
      regional changes in the apical transport in embryos and newly hatched chicks.
      Results show that the apparent Michaelis constant (Km) values did not change
      during the period studied in each region of the small intestine. However, the
      ileum showed a smaller Km than that of the duodenum and jejunum, indicating an
      increase of the affinity of the carrier in the distal portion of the intestine
      and a significant contribution of the ileum to overall sugar absorption in the
      perinatal period. There were important changes in the diffusional component and
      in the mediated transport system capacity during this period, as well as in the
      different regions of the intestine. Significant increases in the maximal rate of
      transport (Vmax) were observed in all regions during the embryonic period until
      the second day after hatching, followed by a decline during the first week.
      During all the period studied, Vmax values from the jejunum were significantly
      greater than those from both the duodenum and the ileum at every age studied
      showing that the jejunum is the segment that is best suited for Na(+)-mediated
      uptake. Such changes which occur when the need for nutrients for rapid
      development are at their highest are not solely a result of diet composition, but
      rather in accordance with a genetic programme.

PMID- 9032752
TI  - Levels and activity of brain protein kinase C alpha and zeta during the aging of
      the medfly.
AB  - Brain protein kinase C (PKC) activity, as well as PKC alpha and PKC zeta levels
      detected by immunoblotting, were monitored during the lifespan of the
      Mediterranean fruit-fly Ceratitis capitata. PKC activity increased in the
      particulate fraction during the last stages of the life of C. capitata.
      Immunoblotting studies with an anti-PKC alpha antibody also demonstrated
      increased enzyme levels in the particulate fraction. Cytosolic levels of PKC zeta
      decreased in the terminal phase of the lifespan of the fly, whereas levels of
      membrane-bound PKC zeta increased at that stage. Results thus indicate that
      during C. capitata final phase of life a translocation of PKC alpha and PKC zeta
      to the particulate fraction occurs, and therefore both kinases could be involved
      in the terminal process of this fruit-fly.

PMID- 9032753
TI  - In vitro study of gingival fibroblasts from normal and inflamed tissue: age
      related responsiveness.
AB  - The aim of this study was to characterize some phenotypic expressions of
      fibroblasts from the human oral mucosa. Gingival and lower forearm fibroblasts
      from young (20-30 years) and elderly (> 60 years) subjects were analyzed.
      Gingival fibroblasts were taken from donors with (P) and without (NP) periodontal
      disease, while skin biopsies were taken from healthy subjects. Cell proliferation
      was assessed by evaluating the cell multiplication coefficient (C.M.C.). The
      proliferation potential of gingival fibroblasts from elderly individuals with and
      without periodontopathy did not differ from that of young subjects in the same
      condition but differed significantly in the skin samples. Enzyme neutral
      endopeptidase (EC 3.4.24.11) (NEP) activity, studied as a possible marker of cell
      ageing, showed an age-related increase in human skin fibroblasts but not
      consistently in gingival fibroblasts from individuals with or without periodontal
      disease. Cell area and substrate adhesion were evaluated by morphometric
      analysis. There were no significant differences between elderly P and NP
      subjects, while significant differences were observed between young and elderly P
      subjects. In conclusion, proliferative capacity and NEP activity in gingival
      fibroblasts did not appear to be age-related, probably because their
      microenvironment is continually moistened by saliva, which continues to contain
      growth factors, notably EGF, even into senescence. Tissue reaction and repair are
      important clinical and therapeutic implications.

PMID- 9032754
TI  - A glucose-rich diet shortens longevity of mice.
AB  - High plasma levels of glucose and insulin over long-time periods play an
      important role in the genesis of diabetic complications. There is evidence that
      the long term consumption of glucose-rich diet by rats is detrimental to insulin
      sensitivity. We investigated the effect of a glucose-rich diet on longevity of 70
      female mice which were compared to 70 mice on a control diet. The average age of
      death of the control group was 568 +/- 139 days compared to 511 +/- 170 for the
      glucose group and the seven oldest mice of the control group died at age 890 +/-
      52 days, while the seven oldest mice of the glucose group died at 833 +/- 49
      days. These differences are statistically significant (P < or = 0.05). Our work
      shows that a life-long intake of a diet with 20% of total energy derived from
      glucose leads to a significant reduction of the average and maximal life-span in
      female mice and thus, supports previous observations of detrimental effects of
      high glucose intake over long periods.

PMID- 9032755
TI  - Age-related changes in proliferating cell nuclear antigen levels.
AB  - To clarify the effect of aging on rat liver regeneration, we compared
      proliferating cell nuclear antigen (PCNA) levels in control and regenerating
      livers from young and aged rats 48 h after partial hepatectomy. The nucleoplasm
      and cytoplasm from regenerating livers of 2-month and 24 month-old rats were
      fractionated by phosphocellulose column chromatography, aliquots of fractions
      were transferred to nitrocellulose filters and the amounts of PCNA in each
      fraction were measured by an immunostaining method. Two forms of PCNA, L type
      (eluted at low concentrations of KC1) and H type (eluted at high KC1
      concentrations) were observed in the nucleoplasm from both control and
      regenerating young rat liver. On the other hand, the cytoplasm contained P type
      (eluted in the pass-through fraction), L type and H type PCNA. In control liver
      from aged rats, three types of PCNA in the cytoplasm and two types in the
      nucleoplasm were present at decreased levels. In regenerating liver from young
      rats, the increases in L type in the cytoplasm and H type in the nucleoplasm were
      remarkable. However, none of the three PCNA types increased significantly during
      liver regeneration in aged rats. Treatment with DNase resulted in the
      disappearance of the H type with a concomitant increase in the P and L types.
      These results suggest that the H type is a complex form consisting of the P and L
      types of PCNA and DNA. These results suggest that the increase in the L type in
      the cytoplasm reflects newly synthesized PCNA production for cellular
      proliferation and that the increase in the H type in the nucleoplasm is a
      reflection of binding to DNA and the fundamental role of PCNA itself in liver
      regeneration in young rats. On the other hand, there was little increase in any
      of the three types in regenerating liver from 24-month-old rats. Thus, PCNA
      content may be closely related to the decrease in the rate of cellular
      proliferation in aged animals.

PMID- 9032756
TI  - A tumor preventive effect of dietary restriction is antagonized by a high housing
      temperature through deprivation of torpor.
AB  - Energy restriction (ER) has proven to be the only effective means of retarding
      aging in mice. The mechanisms of multiplicity of effects of ER on aging remain,
      however, fragmentary. ER induces daily torpor, the induction of which is reduced
      by increasing the ambient temperature to 30 degrees C. The effects of preventing
      hypothermia in ER animals were studied in terms of the expected consequences of
      ER on survival, disease pattern and a number of physiological parameters in
      autoimmune prone MRL/lpr mice and lymphoma prone C57BL, 6 mice. The results
      demonstrate that torpor plays a crucial role in the prevention of lymphoma
      development but does not have an affect on other aspects of ER, such as
      prevention of autoimmune diseases.

PMID- 9032757
TI  - Biological relationship between F18ab and F18ac fimbriae of enterotoxigenic and
      verotoxigenic Escherichia coli from weaned pigs with oedema disease or diarrhoea.
AB  - Comparative fimbrial expression and adhesion studies were made on enterotoxigenic
      and verotoxigenic E. coli (ETEC and VTEC) strains isolated from cases of porcine
      postweaning diarrhoea or oedema disease. F107(F18ab) fimbriae--monitored by
      polyclonal and monoclonal antibodies and by electron microscopy--were poorly
      expressed on most VTEC strains. In contrast, 2134P(F18ac) fimbriae were more
      readily detected on most ETEC strains. The F18ac strains adhered in vivo to
      ligated intestinal loops in weaned pigs while the F18ab strains did not adhere or
      adhered weakly. Similarly, the F18ac strains adhered to isolated intestinal brush
      borders in weaned pigs but the F18ab strains (except for the F107 reference E.
      coli) did not adhere or adhered weakly in vitro. Neither the F18ab nor F18ac
      strains adhered to brush borders from newborn pigs. In vitro adhesion of F18ab
      and F18ac strains was mannose resistant and receptors for F18 seemed to differ
      from receptors for K88(F4). It is concluded that the antigenic variants of F18
      fimbriae (F18ab and F18ac) are biologically distinct. F18ab fimbriae are
      expressed poorly both in vitro and in vivo and are frequently linked with the
      production of SLT-IIv and serogroup O139, while F18ac are more efficiently
      expressed in vitro and in vivo and most often are linked with enterotoxin (STa,
      STb) production, and serogroups O141, O157.

PMID- 9032758
TI  - Modulation of phagocytic function of bovine mononuclear phagocytes by Haemophilus
      somnus.
AB  - The interactions between bovine mononuclear cells and Haemophilus somnus are
      known to be complex. To study this interaction, a flow cytometric assay was
      developed to assess the effect of H. somnus on phagocytosis of killed opsonized
      Staphylococcus aureus by bovine alveolar macrophages and blood monocytes. Using
      this in vitro system, it was found that log phase H. somnus significantly
      inhibited the phagocytosis of killed opsonized S. aureus by bovine alveolar
      macrophages obtained both from healthy calves and from cattle experimentally
      infected with H. somnus. However, killed log-phase H. somnus, in vitro passaged
      and stationary phase H. somnus had no effect on the phagocytic activity of these
      cells. In contrast to bovine alveolar macrophages, blood monocytes showed a
      significant increase in their phagocytic activity following in vitro exposure to
      either log or stationary phase H. somnus. Using a lypophilic, non-toxic
      fluorophore PKH2 to label live H. somnus, it was possible to simultaneously
      measure the uptake of both S. aureus and H. somnus. Stationary and log phase H.
      somnus were taken up by macrophages equally well, even though phagocytosis of S.
      aureus was inhibited by only log phase H. somnus. These results demonstrate the
      ability of H. somnus to modulate bovine mononuclear phagocytic function which
      might contribute towards the pathogenesis of bovine hemophilosis.

PMID- 9032759
TI  - Chlamydia trachomatis glycosaminoglycan-dependent and independent attachment to
      eukaryotic cells.
AB  - Chlamydia trachomatis consists of two biovars, lymphogranuloma venereum (LGV) and
      trachoma, that differ in their infectivity in vivo and in vitro. Although
      addition of exogenous heparin or heparan sulfate in vitro effectively inhibits
      infectivity of both biovars and inhibits LGV biovar attachment to host cells,
      trachoma biovar attachment was only modestly inhibited (approximately 30%) by
      exogenous heparin. To dissect the relationship of heparin inhibition of
      attachment and infectivity, a heparan sulfate lyase (heparitinase) was used to
      treat organisms and evaluated for changes in attachment and infectivity. In
      contrast to heparitinase-treated LGV biovar organisms that lose their ability to
      attach and infect, treatment of trachoma biovar organisms with a concentration of
      heparitinase sufficient to reduce trachoma biovar infectivity by > 90%, only
      inhibited attachment to host cells by approximately 40%. Significantly,
      attachment could be fully restored for heparitinase-treated organisms of both
      biovars with exogenous heparan sulfate; however, the coating of the trachoma
      biovar organisms with heparan sulfate rendered the trachoma biovar similar to the
      phenotype of the LGV biovar by > 90% sensitivity to heparin inhibition of
      attachment. These data suggest that the LGV biovar used predominantly a heparin
      inhibitable mechanism for attaching to host cells, whereas the trachoma biovar
      used a heparin-independent means in addition to a heparin-dependent mechanism to
      adhere to host cells. Once attached, the trachoma biovar, nevertheless, relied on
      the heparin-dependent pathway to enter host cells.

PMID- 9032760
TI  - Effect of hemorrhagic toxin produced by Clostridium sporogenes on rabbit ligated
      intestinal loop.
AB  - In order to characterize the toxicity of the hemorrhagic toxin of Clostridium
      sporogenes isolated from the rabbit with antibiotic-associated hemorrhagic
      diarrhoea, we studied the toxin productivity of C. sporogenes cultured in various
      media and the toxic effect of the partially purified preparation of the culture
      supernatant in rabbit intestinal loops. The hemorrhagic activity, which was
      determined by rabbit skin test for assessment of the toxin production, of culture
      supernatant of C. sporogenes reached maximum in the early stationary phase of the
      bacterial growth in GAM or Trypticase soy broth that contained rich glucose,
      ammonia and peptide. The partially purified toxin prepared by hydroxyapatite,
      phenyl Toyopearl and Superdex 200 columns caused marked hemorrhage in rabbit
      ligated intestinal loops. Histological examination of the intestinal loops
      injected with the toxin revealed noticeable pathological alterations which seemed
      to be a characteristic of this toxin. Marked hemorrhage could be observed in the
      mucosa, submucosa, muscular layer and subserous spaces. There were various
      degrees of infiltration of inflammatory cells such as polymorphonuclear
      leukocytes and granulated leukocytes throughout the intestinal wall, but it was
      not associated with any necrotic changes of the tissue. These findings indicate
      that hemorrhagic toxin produced by C. sporogenes induces vascular changes in the
      intestine without any direct effects on the parenchymal cells.

PMID- 9032761
TI  - Attachment of Haemophilus ducreyi to human foreskin fibroblasts involves LOS and
      fibronectin.
AB  - Haemophilus ducreyi is the causative agent of the genital ulcer disease
      Chancroid. Chancroid has been shown to increase the risk of heterosexual
      transmission of HIV. Little is known regarding the attachment or localization of
      this organism to human cells in either the dermal or epidermal layer. In this
      study the attachment of H. ducreyi to human foreskin fibroblast (HFF) cells was
      further characterized. Attachment was mediated by more than one mechanism.
      Proteinase K treatment but not trypsinization of H. ducreyi significantly reduced
      attachment suggesting protein involvement. In addition, purified
      lipooligosaccharide (LOS) was able to inhibit attachment in a dose dependent
      manner. It appeared that the organism binds to fibronectin in the extracellular
      matrix of HFF cells, since competition studies using fibronectin showed that it
      was able to significantly reduce attachment in a dose dependent manner whereas
      collagen did not. We hypothesize that the attachment of H. ducreyi involves both
      a protein mediator of attachment (likely pili) as well as LOS and that one or
      both of these bacterial components interacts with fibronectin in the
      extracellular matrix to mediate attachment to HFF cells.

PMID- 9032763
TI  - Induction of TNF-alpha mRNA in murine macrophages by virulent and avirulent
      strains of Salmonella choleraesuis serovar typhimurium and serovar Choleraesuis.
AB  - TNF-alpha mRNA induction in murine macrophages by virulent and avirulent
      Salmonella strains was measured in vitro by RT-PCR method. Virulence plasmid
      cured strains of S. choleraesuis serovar Typhimurium and serovar Choleraesuis,
      and rpoS-defective mutant of S. choleraesuis serovar Typhimurium induced
      significantly higher level of TNF-alpha mRNA than their parent (virulent) strains
      in macrophages of C3H/HeN mice. When macrophages of LPS-low responder (C3H/HeJ)
      mice were used, the difference of the induction level was not observed,
      indicating that LPS was involved in the enhanced level of TNF-alpha mRNA
      induction by avirulent Salmonella strains. LPSs from virulent and avirulent
      strains were analysed, but no difference was found for cytokine-inducing
      activity, and chemical properties. Those results suggested that avirulent
      Salmonella strains were damaged more easily, and released more LPS in macrophages
      to enhance TNF-alpha induction.

PMID- 9032762
TI  - Heparin-mediated inhibition of Chlamydia psittaci adherence to HeLa cells.
AB  - The adherence of human strains of Chlamydia trachomatis has been recently shown
      to be inhibitable by heparin and heparitinase, leading to the proposal that
      Chlamydia binding to host cells may be mediated by a glycosaminoglycan (GAG)
      dependent mechanism. We here describe the adherence of the guinea-pig pathogen,
      Chlamydia psittaci GPIC, to HeLa cells, which was measured by cytofluorometry
      with chlamydiae whose DNA was fluorescently labelled. Adherence could be
      inhibited by heat or trypsin pretreatment of the bacteria, and binding was much
      faster at 37 degrees C (reaching a plateau within 1 h) than 4 degrees C. Little
      binding remained when host cells were pre-fixed with paraformaldehyde, suggesting
      that host cell receptor mobility may be required for effective adherence.
      Visualization by confocal microscopy confirmed that the bacteria were at or near
      the host cell surface during the entire time-course of these experiments.
      Adherence increased as a function of pH between pH 6 and pH 8.0-8.5. Both
      adherence and infection of HeLa cells could be inhibited with heparin when the
      adherence step was performed at 4 degrees C, but only infection was inhibited
      when the adherence step was performed at 37 degrees C, even though heparitinase
      could block adherence at either 4 degrees C or 37 degrees C. Even at 4 degrees C,
      heparin-mediated inhibition was significantly lower at pH 8 than pH 7.4,
      suggesting that GAG-independent mechanisms may play a role in the higher
      adherence observed at basic pH. These results therefore demonstrate that a GAG
      dependent adherence step may be operative in C. psittaci, and raise the
      possibility that other adherence mechanisms may also contribute to binding by
      this chlamydial strain. Furthermore, they suggest that there may not be a strict
      correlation between C. psittaci adherence and the ability to cause productive
      infections.

PMID- 9032764
TI  - Uterine natural killer cells during pregnancy in rodents.
AB  - Large mononuclear cells with abundant prominent granules were described decades
      ago by morphologists studying implantation sites in pregnant rodents. These
      striking cells accumulated by midgestation in large numbers in a structure unique
      to rodent pregnancy that develops in the mesometrial region of the uterine
      musculature and was given the unfortunate name of metrial gland. Thus, the cells
      were originally termed granulated metrial gland (GMG) cells. Evidence provided
      over the last few years, especially in situ phenotyping and studies in mutant and
      transgenic mice, has reliably identified these cells as members of the natural
      killer (NK) cell lineage, and they are referred to here as granulated uterine NK
      (uNK) cells. Much of the evidence is reviewed here, along with a description of
      the spatial and temporal aspects of the differentiation of these cells.
      Especially highlighted are their life history and their likely importance early
      in pregnancy before development of the metrial gland proper. Their relation to
      other NK cell populations, especially activated cells, as well as their possible
      functions during pregnancy, are discussed. Because these cells develop in the
      unique microenvironment of the pregnant uterus and appear to differentiate along
      a specific pathway, hypotheses are proposed regarding the regulation of
      granulated uNK cell differentiation in this site.

PMID- 9032765
TI  - Uterine natural killer cells: insights into lineage relationships and functions
      from studies of pregnancies in mutant and transgenic mice.
AB  - Mice expressing genetic alterations have been extremely valuable in providing
      insights into both the lineage relationships and functions of lymphohematopoietic
      cells. This approach has been applied to granulated lymphocytes that localize to
      implantation sites in the rodent uterus during pregnancy. Histological analyses
      of implantation sites collected from various mutant and transgenic mice over the
      course of gestation strongly support the conclusions that these granulated
      lymphocytes, previously named granulated metrial gland (GMG) cells, are natural
      killer (NK) cells and that they are essential for normal development of the
      placenta. Pregnancy-associated uterine NK (uNK) cells have limited lytic activity
      suggesting that their secretory products, particularly cytokines and matrix
      proteins, may be critical for normal placental maturation. This review will
      highlight information collected from pregnancies in mutant and transgenic mice
      that have contributed to the current understanding of functions of uNK cells
      during gestation.

PMID- 9032766
TI  - Natural killer cells in the nonpregnant murine uterus.
AB  - Recent studies on the origin and function of the large granular cells that
      accumulate at implantation sites in the rodent uterus during pregnancy have shown
      that these cells are highly differentiated natural killer (NK) cells. These
      findings raise questions about the presence and regulation of NK cells in the
      normal, nonpregnant uterus. For example, do NK cells comprise a major or minor
      population of leukocytes in the uterus? Are these uterine NK cells (uNK) similar
      in phenotype and function to NK cells in other organs? Is the population of uNK
      cells maintained by local proliferation and/or by influx via the blood stream
      from the bone marrow? This brief review will examine our current understanding of
      those questions based on the experimental literature on rodents and our own
      recent studies.

PMID- 9032767
TI  - Human uterine natural killer cells.
AB  - The human uterine mucosa is infiltrated by large numbers of CD56+ natural killer
      (NK) cells which are particularly abundant around the time of implantation and
      during early pregnancy. These NK cells have the phenotype CD56bright CD16-mCD3-
      and the characteristic morphology of large granular lymphocytes. The NK cells are
      in close association with the trophoblast cells which invade into the uterus. The
      expression of HLA class I antigens, HLA-G and HLA-C, by these trophoblast cells
      raises the possibility that maternal NK cells can recognise and respond to the
      fetal trophoblast cells. Thus, the maternal-fetal interaction, and hence
      reproductive success, may depend on an NK allorecognition system.

PMID- 9032768
TI  - Uterine natural killer cells in species with epitheliochorial placentation.
AB  - The epitheliochorial placenta represents the least intimate association between
      maternal and fetal tissues. The best known examples of this form of placentation
      are the domestic livestock species. Current information on the nature and
      proposed functions of uterine lymphocyte populations in ruminants (sheep and
      cattle), horses and pigs is presented. In ruminants unusual gamma delta T cells
      may play a role in mid to late gestation. During normal horse pregnancy, fetally
      derived endometrial cup cells invade the uterine stroma and are destroyed by
      maternal leukocytes midway through gestation. Natural killer (NK) cells or
      lymphokine-activated killer cells may be involved in this process, but the
      presence of these cell types in the equine uterus has yet to be established. The
      pig is similar to the human and rodent in that NK-like cells are present in the
      uterine stroma and seem to play a role in pregnancy. These cells are activated
      during early placental development and may be important in early interactions
      between the conceptus and the maternal immune system. The contribution of
      pregnancy-associated uterine lymphocytes to successful gestation has not been
      established. However, a common theme among these species is that the presence of
      the genetically foreign conceptus seems to activate uterine lymphocytes and to
      redirect their activities towards the promotion of fetal survival.

PMID- 9032769
TI  - Expression of the putative transcription factor NOR-1 in the nervous, the
      endocrine and the immune systems and the developing brain of the rat.
AB  - NOR-1 is a novel member of the NGFI-B/RNR-1 subfamily within the nuclear receptor
      superfamily, and has been implicated in signal transduction mediated by various
      second messengers. To investigate the physiological role of NOR-1, we examined
      its gene expression in various adult rat tissues and developing rat brain by the
      quantitative reverse transcription-polymerase chain reaction using in vitro
      synthesized RNA as an internal standard. The NOR-1 gene was expressed in all
      tissues examined, but predominantly in the cerebral cortex and pituitary glands.
      Thymus, adrenal glands, spleen, epididymis, submandibular glands and deferent
      ducts showed moderate expression. In the brain, NOR-1 gene expression was
      developmentally regulated, with the peak levels on gestational day 18. These
      findings suggest a ubiquitous role of NOR-1 in signal transduction in diverse
      tissues. These findings also suggest that the nervous, endocrine and immune
      systems may be highly exposed to NOR-1-inducing stimuli under normal conditions
      in adult rats. Developing rat brain cells may most frequently receive the
      relevant signal on day 18 of gestation.

PMID- 9032770
TI  - Effects of estrogen on oxytocin receptor messenger ribonucleic acid expression in
      the uterus, pituitary, and forebrain of the female rat.
AB  - Oxytocin receptors are regulated during parturition and lactation. Gonadal
      steroids are thought to be key players in this regulation. It is not well
      documented how oxytocin receptor gene expression is regulated in the CNS. In this
      study we analyzed potential estrogen effects on the oxytocin receptor mRNA levels
      in some areas integral to the limbic-hypothalamic system, namely the ventromedial
      nucleus of the hypothalamus (VMH), posterior medial nucleus of amygdala (MeAmyg),
      and arcuate nucleus (ARC), as well as the caudate putamen (CPu), CA1 region of
      the hippocampus, anterior pituitary, and uterine tissue of ovariectomized (OVX)
      female rats. By in situ hybridization we observed a 4.4-fold increase in oxytocin
      receptor mRNA levels in the VMH after 48 h of estrogen treatment when compared to
      OVX rats. Smaller increases were observed in the MeAmyg, hippocampus, and
      anterior pituitary (3.18, 1.76, and 2.55, respectively). No changes in oxytocin
      receptor mRNA levels were observed in the CPu or ARC after estrogen treatment. A
      similar finding resulted from slot-blot analysis of total mRNA extracts. In
      uterine tissue, 48 h of estrogen treatment increased oxytocin receptor mRNA level
      in the myometrium (3.13-fold). No changes in oxytocin receptor mRNA levels were
      observed after 12 and 24 h of estrogen treatment. These findings suggest that the
      estrogenic regulation of oxytocin receptor binding in both CNS and uterine
      tissues may in part be mediated by de novo synthesis of oxytocin receptor mRNA or
      by alterations in the stability of oxytocin receptor gene transcripts.

PMID- 9032771
TI  - Hypothalamic-pituitary-adrenal activation by the bacterial superantigen
      staphylococcal enterotoxin B: role of macrophages and T cells.
AB  - Staphylococcal enterotoxin B (SEB) is a bacterial superantigen which stimulates T
      cells bearing the V beta 8 motif on the T-cell receptor. This stimulation is MHC
      class II dependent, and in vivo results in a rapid and pronounced T-cell cytokine
      response. Based on previous evidence that SEB stimulates corticosterone
      production in BALB/c mice, which possess a high percentage of V beta 8+ T cells,
      we explored the effects of SEB on the hypothalamic-pituitary-adrenal (HPA) axis
      and identified the peripheral immunologic cellular requirements for these
      effects. Administration of SEB stimulates corticosterone in a dose-dependent
      manner, with peak production of corticosterone occurring by 2 h after
      intraperitoneal challenge with 50 micrograms SEB. Challenge with staphylococcal
      enterotoxin A, which activates V beta 3+ and V beta 11+ T cells (deleted during
      ontogenesis in BALB/c mice), did not increase ACTH or corticosterone production.
      Furthermore, SEB challenge increased plasma ACTH, which accounted for the
      increased plasma corticosterone, and increased the expression of c-fos in the PVN
      region of the hypothalamus. In vivo elimination of macrophages did not prevent
      the corticosterone response to SEB, suggesting that pituitary-adrenal activation
      does not require macrophages. However, when mice were pretreated with the T-cell
      immunosuppressant cyclosporin A, the significantly increased ACTH and
      corticosterone production in response to SEB was dramatically attenuated. These
      results demonstrate that bacterial superantigens can stimulate the HPA axis, and
      that functional T cells may play an obligatory role in this effect.

PMID- 9032772
TI  - Influence of the estrous cycle on c-fos and CRH gene transcription in the brain
      of endotoxin-challenged female rats.
AB  - The purpose of this study was to investigate whether the ovulatory cycle
      interferes with the effect of the acute-phase response of a systemic immune
      activation on the transcription of the immediate early gene c-fos and the stress
      related neuropeptide corticotropin-releasing hormone (CRH) in the brains of
      female rats. Throughout the day of proestrus and diestrus-2 (09.00, 12.00, 15.00
      h), adult rats received either a single intraperitoneal injection of the
      endotoxin lipopolysaccharide (LPS, 200 micrograms/100 g body weight) or the
      vehicle solution and were killed 3 h later (12.00, 15.00, 18.00 h). Frozen brains
      were mounted on a microtome, cut in 30-micron slices and then processed for the
      detection of c-fos mRNA and CRH primary transcript (heteronuclear [hnRNA]) by
      means of in situ hybridization histochemistry using 35S-labeled exonic and
      intronic probes, respectively. LPS injection induced a profound expression of c
      fos mRNA in the several nuclei and areas of the brain, such as the organum
      vasculosum of the lamina terminalis/medial preoptic area, supraoptic nucleus,
      parvo- and magnocellular divisions of the hypothalamic paraventricular nucleus
      (PVN), arcuate nucleus/median eminence, central nucleus of the amygdala, locus
      coeruleus, nucleus of the solitary tract, area postrema and ventrolateral
      medulla. Interestingly, the intensity of expression of c-fos mRNA depended on the
      phase of the estrous cycle and/or the time of the day. Indeed, in several of the
      structures described above, LPS induced a more pronounced c-fos signal in the
      morning of proestrus than the afternoon and diestrus-2. CRH primary transcript
      was significantly increased by LPS treatment selectively in the parvocellular
      division of the PVN and the highest hybridization signal was observed in the
      morning of proestrus, a period where a large number of c-fos-positive cells were
      colocalized in CRH-immunoreactive neurons. A significant increase in the levels
      of AVP hnRNA was also observed in the parvocellular PVN of animals sacrificed at
      noon and early afternoon of both pro- and diestrus days. These results provide
      evidence that the neuroendocrine events regulating the reproductive cyclicity
      influence the endotoxin-induced activation of the early gene c-fos in selective
      structures of the brain and the stimulation of neurons directly involved in the
      regulation of the HPA axis. It is possible that the gonadal status of female
      mammals plays a crucial role in the integration of the organism in the presence
      of foreign material in preventing an exaggerated immune response during
      particular phases of the ovulatory cycle. The capacity of female animals to
      modulate the intensity through which the neuronal circuitry activated during
      immunogenic processes is likely to be an elegant sexual dimorphism participating
      in the adjustment of the responses in line with the physiological demand.

PMID- 9032773
TI  - Folliculo-stellate cells of human pituitary adenomas: immunohistochemical study
      of the monocyte/macrophage phenotype expression.
AB  - Folliculo-stellate cells (FS) represent a small percentage of anterior pituitary
      elements of still undetermined embryological origin. They are sparse among
      endocrine pituitary cells and are characterized by the lack of secretory granules
      and by the presence of few branching processes inserted between hormone-secreting
      cells. Although FS cell role is still under discussion, recent reports showed
      that they produce monocyte-derived cytokines able to influence the hormone
      production and modulate the immunoendocrine connections. In this study we applied
      three monocyte-macrophage markers (HAM56, KP1, HLA-DR) to 15 pituitary adenomas
      in order to ascertain whether FS cells belong to the macrophage lineage. In this
      case FS cells could be considered the resident macrophages of the pituitary. FS
      cells were identified according to the reactivity to S-100, GFAP and vimentin. We
      confirm that S-100 represents the most useful marker for these cells that were
      detected scattered between tumor cells in more than half of the adenomas. GFAP
      stained only a percentage of FS cells, while vimentin recognized in addition to
      stellate cells endothelia, perivascular and infiltrating macrophages. We were
      unable to detect the expression of the macrophage markers on S-100 and GFAP
      reactive cells. Indeed, HAM56, KP1 and HLA-DR-positive cells were mostly round,
      small size and located in the perivascular and septal positions where FS cells
      were never detected. Lack of expression of monocyte-macrophage lineage markers by
      FS cells in pituitary adenomas suggests their preferential neuroectodermal
      origin. However, further studies on normal human pituitary will be needed before
      ruling out a possible role for FS cells as resident pituitary macrophages.

PMID- 9032774
TI  - Effects of continuous infusion of interleukin 1 beta on corticotropin-releasing
      hormone (CRH), CRH receptors, proopiomelanocortin gene expression and secretion
      of corticotropin, beta-endorphin and corticosterone.
AB  - A number of recent studies suggest that interleukin 1 beta (IL-1 beta) is a major
      mediator of hypothalamo-pituitary-adrenal (HPA) responses following infectious
      aggression. We investigated whether IL-1 beta mediates long-term changes in HPA
      activity and studied the cellular regulation of the anterior pituitary. To mimic
      chronically elevated IL-1 beta production thought to occur during infectious
      diseases, osmotic pumps (Alzet type) were implanted in the peritoneal cavity of
      male rats and hIL-1 beta was infused continuously at rates of 1 or 3
      micrograms/day. Effects of hIL-1 beta action on plasma ACTH, beta-endorphin (beta
      EP) and corticosterone (CORT) secretion and on anterior pituitary (AP), ACTH and
      beta-EP content were followed. In addition, hypothalamic (HT) CRH mRNA and in AP,
      CRH receptor (CRH-Rc) mRNA, POMC nuclear primary transcript RNA, POMC nuclear
      intermediate processing RNA and POMC nuclear and cytoplasmic mRNA were quantified
      using a highly sensitive solution hybridization nuclease protection assay.
      Continuous infusion of hIL-1 beta stimulated the HPA axis at varying degrees.
      Increased HT CRH gene expression, AP POMC gene transcription, ACTH and beta-EP
      release occurred only during the first 3 days of the treatment. A long-lasting
      enhancement of ACTH and beta-EP synthesis and of POMC gene expression resulted
      from activated POMC gene transcription followed by an increased POMC mRNA
      stability and decreased POMC mRNA turnover. In the AP, stimulation of ACTH and
      beta-EP secretion and POMC gene transcription disappeared after continuous IL-1
      beta treatment, possibly in part due to a refractory process mediated by
      decreased CRH-Rc gene expression in corticotropes.

PMID- 9032775
TI  - Atrial natriuretic peptide and C-type natriuretic peptide do not acutely inhibit
      the release of adrenocorticotropin from equine pituitary cells in vitro.
AB  - It has been suggested that atrial natriuretic peptide (ANP) is the long-sought
      inhibitor of corticotropin (ACTH) secretion, but the evidence is conflicting. We
      have examined the effect of ANP and C-type natriuretic peptide (CNP) on the
      secretion of ACTH by perifused equine pituitary cells in an in vitro milieu
      intended to mimic the in vivo milieu in the horse. Corticotropin-releasing
      hormone (20 pM) and cortisol (0 or 100 nM) were perifused continuously and 7
      pulses of arginine vasopressin (AVP; 10 nM) applied for 5 min at 30-min
      intervals. ANP (1 nM) or CNP (1 nM) were perifused continuously for 75 min,
      beginning before the 3rd AVP pulse. Neither ANP nor CNP, with or without
      cortisol, significantly altered the ACTH secretory response to the AVP pulses. We
      conclude that these natriuretic peptides are unlikely to act at the pituitary as
      rapid inhibitors of ACTH secretion in the horse.

PMID- 9032776
TI  - Immunochemical demonstration of the mineralocorticoid receptor in ocular tissues.
AB  - We studied the presence of the mineralocorticoid receptor (MCR) in the eye with
      the aid of a number of immunochemical techniques. Immunoblotting with a
      polyclonal antibody, directed against the rat renal MCR, revealed a single band
      of about 102 kD in extracts prepared from whole bovine or rat retina similar to
      that observed in cytosol from the kidney and myocardium from these species.
      Isolated cells of the bovine retinal pigment epithelium (RPE) similarly exhibited
      a 98- to 102-kD band in Western blots developed with the aid of anti-MCR
      antiserum. The 98- to 102-kD band was also obtained following autoradiography of
      RPE cytosol irradiated in the presence of 3H-R 5020. This fluorographic pattern
      was abolished when RU 26752, an antagonist specific to the MCR, was allowed to
      compete with radiolabelled promegestone. The MCR-3H-RU 26752 complex in RPE
      cytosol underwent heat activation, as judged by binding to DNA cellusose, and
      could also be precipitated by anti-MCR IgG. In primary cultures, the
      proliferation of the RPE cells was inhibited by the two MCR-specific antagonists
      RU 26752 and ZK 91587. The loss of the MCR-specific immunofluorescence in RPE
      cells after only 3 passages in culture was associated with refractoriness to the
      inhibitory effect of both of these spironolactones. Immunohistochemistry, using
      MCR-specific antiserum, revealed strong fluorescence in specific areas of the rat
      eye. In the retina, immunopositivity was observed in Muller cells, external and
      internal limiting membranes, the vitreous base lining and in the pigment
      epithelium. Epithelial cells of the ciliary body, iris and cornea also exhibited
      strong MCR-specific immunofluorescence. Thus, both the epithelial and the
      nonepithelial compartments of the ocular tissues form interesting new targets to
      delineate the mechanism of action of mineralotropic hormones.

PMID- 9032778
TI  - [Intraabdominal polymicrobial infection due to antimicrobial resistant
      anaerobes].
AB  - Successful treatment of surgical infections includes both the implementation of
      careful operative technique and the choice of appropriate antimicrobial agent.
      Because of advances in the techniques used for anaerobic specimen collection and
      culture, anaerobic bacteria are now predominantly recovered from a variety of
      intra-abdominal and post-operative soft tissue infection. Furthermore, some
      anaerobes including Bacteroides and Prevotella, like some aerobic bacteria, have
      acquired resistance to the commonly used antimicrobial agent. The underestimation
      of resistant anaerobes other than Bacteroides in infective sites may lead to
      incorrect choices of antimicrobial agent for empirical therapy and thus to
      clinical failures of therapy. Surgeons should be more interested in the
      polymicrobial infecting flora to improve the clinical outcome of such infections.

PMID- 9032777
TI  - Decreased hypothalamic-pituitary-adrenal axis sensitivity to cortisol feedback
      inhibition in human aging.
AB  - Aging-related reduction in the sensitivity of the hypothalamic-pituitary-adrenal
      (HPA) axis to glucocorticoid feedback inhibition has been demonstrated in
      rodents, but aging effects on glucocorticoid feedback inhibition in humans are
      unclear. This study assessed the influence of aging on the sensitivity of the
      human HPA axis to feedback inhibition induced by cortisol. Endogenous cortisol
      feedback inhibition was removed by treatment with metyrapone, which reduces
      cortisol synthesis by inhibiting 11 beta-hydroxylase. Feedback inhibition was
      then reintroduced by infusing exogenous cortisol. Sixteen young (26 +/- 1 years
      old) and 16 older (70 +/- 2 years old) subjects underwent three study conditions
      in random order. In the two cortisol infusion conditions, oral metyrapone
      treatment was followed by intravenous infusion of 0.03 mg/kg/h (83 nmol/kg/h) or
      0.06 mg/kg/h (166 nmol/kg/h) cortisol for 150 min. Feedback sensitivity was
      estimated by the latency to and extent of decline of plasma ACTH concentration
      during and following the cortisol infusion. In a placebo condition, placebo
      tablets were substituted for metyrapone and normal saline infusion was
      substituted for cortisol. Blood samples were drawn twice prior to and at 15-min
      intervals for 4 h following the onset of the infusions, and plasma was assayed
      for 11-deoxycortisol, cortisol and ACTH. Plasma cortisol suppression and ACTH and
      11-deoxycortisol elevations did not differ between age groups after metyrapone.
      Older subjects exhibited delayed and blunted ACTH responses to infused cortisol.
      Within older subjects, the ACTH response to the higher dose cortisol infusion was
      blunted in older women compared to older men. These data provide direct evidence
      for reduced responsiveness to glucocorticoid feedback inhibition in human aging.

PMID- 9032779
TI  - [Basic and clinical control of nosocomial infections].
AB  - Nosocomial infections, especially opportunistic infections and occupationally
      acquired infections, are causing major problems in perioperative period.
      Opportunistic infections are increased by opportunism secondary to antibiotic
      therapy and lower body defences. Organisms that cause opportunistic infections
      come from either exogenous or endogenous sources. Exogenous infections result
      from transmission of organisms from a source other than the patient. Control of
      person-to-person spread, such as handwashing and gown technique, disinfection and
      sterilization of equipment, and environmental cleaning are necessary to prevent
      exogenous infections. Endogenous infections are caused by the patient's own
      flora. Antibiotic policies are required to prevent endogenous infections. The
      main preventive measure of occupationally acquired infections, especially blood
      borne infections, is practices of universal precautions. Universal precautions
      are intended to prevent parenteral, mucous membrane, and nonintact skin exposures
      to blood-borne pathogens in health care settings.

PMID- 9032780
TI  - [The pathophysiology and treatment of severe intra-abdominal abscess].
AB  - Formation of an abscess within the peritoneal cavity is a dynamic process,
      representing the body's success at localizing the contamination but its ultimate
      failure to completely destroy the bacteria and neutralize their toxic products.
      In most instances, the origin of the microbial insult is from bacteria which
      colonize the intestinal lumen. The therapeutic means are prompt surgical drainage
      and appropriately administered antimicrobial agents. Surgical drainage of abscess
      are accompanied by either (1) an extraperitoneal approach, (2) an intra-abdominal
      exploration, or (3) ultrasound-guided needle aspiration of the abscess. Choice of
      antimicrobial agents is frequently based upon prediction of pathogens from normal
      flora of bowel contents contaminating a normally sterile area, or from knowledge
      of pathogens expected in certain conditions, rather than on results of cultures
      and susceptibility tests. This selection frequently calls for the choice of
      agents effective against multiple organisms. Patients with prolonged septic
      courses die from a combination of the infection itself and the malnutrition
      resulting from the associated hypercatabolism and starvation. Nutritional therapy
      also of clinical importance in halting the progression toward a fatal outcome.

PMID- 9032781
TI  - [Cytokine-mediated biological response to severe infections in surgical
      patients].
AB  - Cytokines serve to initiate the acute inflammatory response and to integrate
      nonspecific and specific immunological responses to infections occurring in
      perioperative patients. Microbial substances induce macrophages to produce
      pivotal cytokines (TNF-alpha and IL-1 beta). This results in an activation of
      other cytokine productions including IL-2, IL-3, IL-4, IL-6, chemokines, and IL
      10. Also, other host-originated humoral mediators are released from macrophages,
      neutrophils, platelets, and endothelial cells Various cytokines are also produced
      by helper-T (Th) cells, and the Th1/Th2 balance is regulated by cytokines and
      stress hormones. This nonspecific inflammatory response and specific
      immunological response which are mediated by cytokines are crucial for the host
      defense against invading pathogens. On the other hand, the blood levels of TNF
      alpha, IL-6, IL-8, and MIP-1 alpha were correlated with the severity and
      mortality in patients with sepsis. Also we found that in patients with inhalation
      injury the high IL-8 levels in bronchoalveolar lavage fluid on admission
      predicted the development of respiratory insufficiency. In severe infection, a
      systemic release of various cytokines is not properly regulated, and the high
      blood levels of the proinflammatory cytokines cause an autodestructive systemic
      inflammatory response syndrome (SIRS). This condition is termed "Cytokine Storm"
      by the author. In cytokine storm, not only proinflamamtory cytokines, but also
      anti-inflammatory cytokines appear in circulating blood, leading to septic shock,
      multiple organ dysfunction, and immunosuppression. With further understanding of
      the roles of cytokines in sepsis, modulation of cytokine responses could be a new
      modality of the treatment.

PMID- 9032782
TI  - [Perioperative managements for postoperative severe infections in compromised
      host].
AB  - The incidence of postoperative infections, especially due to multi-drug resistant
      strains such as Pseudomonas sp., Enterococcus sp., and Methicillin resistant
      Staphylococcus aureus (MRSA), is high in compromised hosts. Among them,
      respiratory infection, catheter sepsis, and drug-associated enteritis are
      frequently observed and respiratory infection is liable to fall into serious
      illness. These infections have characteristics in causative organisms.
      Pseudomonas aeruginosa or MRSA are frequently isolated in respiratory infections
      and Candida or coagulase-negative staphylococcus are frequently isolated in
      catheter sepsis. G-test in addition to blood culture is necessary for early
      diagnosis of Candida sepsis, vancomycin should be administered in early phase of
      antibiotic-associated enteritis, since this infection is usually caused by MRSA
      or Clostridium difficile and frequently falls into serious illness. The patients
      with protein-calorie malnutrition, liver cirrhosis, renal failure, diabetes
      melitis, administration of anticancer drugs and/or radiation therapy, serious
      injury, or severe operative stress are considered to be compromised hosts in
      surgical field, and the adequate perioperative managements according to these
      disorders should be carried out against postoperative infections.

PMID- 9032784
TI  - [Recent advances and treatment of sepsis].
AB  - This article introduces recent advances in experimental or clinical
      pathophysiology and in treatment of sepsis. Both the concept of systemic
      inflammatory response syndrome (SIRS) and the definition of sepsis, as the
      systemic response to infection, have actually been overwhelming and its
      generalization is contributing on the better prognosis after treatment for the
      patients with sepsis and also on the pioneer researches in this field, using
      molecular biology techniques. In the mediator network and the immune cell
      network, cytokines released from polymorphonuclear cells, macrophages, monocytes
      and vascular endothelial cells have important roles in initiation of the immune
      cells activations or priminings. On the other hand, free radicals, supecroxides,
      proteolytic enzymes directly involved the pathophysiology, and occasionally
      impaired the cellular or the organ function. The patient with one or more organ
      dysfunctions should be cared intensively by multidisciplinary control, i. e.
      antibacterial therapies, nutritional control, immunomodulation, removal of toxic
      substances, etc. Our attentions should be concentrated to prevent from septic
      MODF, especially for a patient primed by infection, because rapid response at the
      second at tack is important for care. Anyhow, fine observation and strict
      investigation is required for the treatment of the primed patient by infection.

PMID- 9032783
TI  - [Severe surgical infection with no information in terms of bacteria].
AB  - The incidence of bacteria caused postoperative infections was performed at the
      timing when bacteria or fungi is not yet detected. This period is important for
      management of postoperative infections. MRSA, E. faecalis, P. aeruginosa and
      fungi were detected with high frequency irrespective of the surgical area. After
      the operation of esophageal cancer, the most frequent infection was postoperative
      pneumonia, and the isolated bacteria was P. aeruginosa frequently. In the cases
      of gastric cancer, hepato-biliary-pancreas cancer and colorectal cancer,
      intraabdominal sepsis was the highest incidence, and the isolated bacteria was E.
      faecalis. In terms of intravenous catheter infection, fungus was common. Thus, it
      may suggest that we can identify the bacteria caused, and the management for
      postoperative infections was performed appropriately by using the antibiotics
      which have the sensitive against the expected pathogen.

PMID- 9032785
TI  - [Prevention and treatment of postoperative septic MOF and DIC and efficacy of
      blood purification].
AB  - Pathophysiologic concept of SIRS has been proposed for the better management of
      postoperative severe infection and septic MOF, and the concept has been found to
      be very useful. It is very important to identify the high risk SIRS patients of
      the development of septic MOF and to treat those patients aggressively to prevent
      the development of septic MOF. In the prevention and treatment of septic MOF, the
      blood purification has been found to be very effective. Among the blood
      purifications, continuous blood purification, such as continuous
      hemodiafiltration (CHDF) should be chosen for this purpose. CHDF has been claimed
      to be very effective to removal of causative humoral mediators from the blood
      stream. The concept of DIC has been changed recently and the concept of DII
      (disseminated intravascular inflammation) should be applied instead of DIC, since
      the main feature of this pathologic condition is the damage of endothelial cells
      due to extensive systemic inflammation.

PMID- 9032786
TI  - [Nutritional support in sepsis].
AB  - The host responses to infection are characterized by a hyperdynamic state and
      hypermetabolism. These events are associated with accelerated release of amino
      acids by the peripheral tissues and with their increased uptake by the liver,
      other visceral organs, and immune cells. Adequate nutrition is essential to
      maintain normal physiologic functions including host defense against infection.
      In this review the current status of the nutritional support in sepsis is
      summarized. Moreover, the review focused on the role of immunonutrition in the
      modulation of inflammatory and immune responses. The immunonutrition includes
      route of nutritional supply, special nutrients and anabolic peptide hormones.
      Recent clinical trials using some of these new modalities are encouraging for the
      prevention, as well as treatment, of severe infection in critical illness.

PMID- 9032787
TI  - [Clinically isolated bacterii seen in complicated infections].
AB  - The spectrum of causative bacterial agents responsible for post-operative
      infections in the surgical field have dramatically changed with time. This could
      be due to recent technical progress in bacterial extraction or the result of more
      effective antibiotics used post-operatively. Nevertheless nosocomial infections
      including those caused by MRSA still demand our close attention. Commonly
      extracted bacterii include Staphylococcus spp., E. faecalis, E. coli, Klebsiella
      spp., E. cloacae, P. aeruginosa and Bacteroides spp., but with regards to
      pathogenicity, extraction frequency and drug resistance, agents requiring the
      highest note of caution may be MRSA, P. aeruginosa and Bacteroides spp. MRSA is
      still the bacterium which makes the most frequent appearance in the clinical
      field, and the only effective antibiotic to MRSA is vancomycin. In addition, P.
      aeruginosa is the most common bacterial agent seen in post-operative infections
      and also the agent to which many of the cephem drugs do not express a high degree
      of antibacterial effect. Furthermore, about half of the Bacteroides spp. are beta
      lactamase-producing strains which deactive the effect of penicillin and cephem
      drugs within the infection site. A drug which proves effective against E. coli
      may nevertheless become somewhat ineffective against this agent when found in a
      mixed infection and if the drug lacks stability against beta-lactamase.
      Clinically, mixed infections including some or even all the above agents are
      known to occur, continuously drawing our close attention.

PMID- 9032788
TI  - [Cyclophosphamide-induced immunological tolerance: an overview].
AB  - A cyclophosphamide (CP)-induced tolerance system in mice that primarily consists
      of donor cell injection followed by CP-treatment was found useful for inducing a
      long-lasting allo- or xeno-tolerance to various solid organs. In the cells
      followed-by-CP system, the sequential mechanisms of the tolerance were clarified
      using the specific correlation between superantigens and certain T cell receptor
      (TCR) V beta segments. Those include the clonal destruction of antigen-stimulated
      mature T cells, the peripheral clonal deletion associated with peripheral
      chimerism, the intrathymic clonal deletion associated with intrathymic chimerism,
      and the clonal anergy. The generation of suppressor T cells was another important
      mechanism of the tolerance in the late stage. Special care taken to overcome the
      "hard" barriers of allo-or xeno-combinations by reducing the "split tolerance"
      produced through the clonal destruction mechanism. For this purpose, the
      tolerogen, antimitotic drug their doses, timing, route of administration,
      combined immunosuppressants, and supportive treatment were all crucial for
      successful induction of a long-lasting skin tolerance. This system may be
      applicable to human transplantation.

PMID- 9032789
TI  - [A case of solitary splenic metastasis from colon cancer].
AB  - A 58-year-old male who had a left hemicolectomy for descending colon cancer on
      July 1, 1993 was admitted to our hospital. A CT scan revealed a homogeneous low
      density mass in the inferior portion of the spleen. Under the diagnosis of
      solitary splenic metastasis, a splenectomy was performed on August 10, 1995.
      Histologically, splenic tumor revealed moderately differentiated adenocarcinoma
      consistent with the primary tumor. Flow cytometric analysis revealed DNA diploidy
      in the primary tumor, and DNA aneuploidy (DNA index = 1.76) in the metastatic
      tumor. Using fluorescence in situ hybridization with p17 H8, numerical aerrations
      of chromosome 17 were observed in the primary tumor.

PMID- 9032790
TI  - Changes of catalase activity after ischemia-reperfusion in rat retina.
AB  - Catalase activity was evaluated in Long Evans rat retina after ischemia and
      reperfusion. Ischemia was induced by ligation of the optic nerve and vessels.
      Rats were sacrificed after 15 and 120 min of reperfusion, respectively. Catalase
      activity was assessed by Claiborne's method and was expressed as U/mg of protein.
      In the first group, retinas of each animal were pooled. In the second group,
      ischemia was induced in the right eye with the left eye serving as control. In
      the first group, enzyme activity was 7.39 +/- 0.26 (n = 11), 7.67 +/- 0.27 (n =
      9) and 9.15 +/- 0.45 (n = 7) for the sham-operated, 15- and 120-min reperfusion
      groups, respectively. There was a significant difference between the control and
      120-min reperfusion groups (p < 0.001). In the second group, there was a
      significant (p < 0.01) increase in catalase activity in the ischemic eye compared
      to the non-ischemic eye after 15 (n = 7) and 120 min (n = 9) of reperfusion.
      These findings may suggest a rapid activation of catalase activity during the
      ischemia-reperfusion sequence.

PMID- 9032791
TI  - Role of catalase in retinal antioxidant defence system: its comparative study
      among rabbits, guinea pigs, and rats.
AB  - The role of catalase in the retinal antioxidant defence system was examined in
      rabbits, guinea pigs, and rats with and without prolonged administration of a
      diet containing 0.4% 3-aminotriazole (3-AT), a catalase inhibitor. When weanling
      rabbits, guinea pigs, and rats we administered 3-AT for 8, 7, and 10 weeks,
      respectively, retinal catalase activity was reduced by approximately 50% in all
      these animals. In the retina of rabbits with 3-AT administration, a decrease in
      superoxide dismutase (SOD) activity and an increase in lipid peroxide (LPO)
      concentration occurred. while glutathione peroxidase (GSH-px) activity did not
      change. In the retina of guinea pigs with 3-AT administration, an increase in LPO
      concentration occurred, while SOD and GSH-px activities did not change. In the
      retina of rats with 3-AT administration, a decrease in GSH-px activity and an
      increase in LPO concentration occurred, while SOD activity did not change. An
      increase in serum LPO concentration was found in rats with 3-AT administration,
      while the concentration did not change in rabbits and guinea pigs. These results
      indicate that catalase plays an important role in the retinal antioxidant defence
      system, but that the way catalase contributes to the maintenance of the retinal
      antioxidant defence system is different among these animals. The present results
      suggest that under the prolonged inhibition of catalase, the retina of rats, but
      not of rabbits and guinea pigs, may suffer from the influence of systemic
      oxidative stress.

PMID- 9032792
TI  - Retinal hemodynamics in middle-aged normal subjects.
AB  - The laser Doppler technique and monochromatic photography were used to measure
      the total retinal blood flow, temporal/nasal differences in blood flow and the
      relationship between blood flow and vessel diameter in 5 healthy subjects, aged
      54-58 years. Systemic blood pressure (BP) and intraocular pressure were also
      measured, and the retinal perfusion pressure was calculated. The measurements
      were compared to those previously obtained from a younger group of 7 healthy
      subjects, aged 25-38 years. Total retinal blood flow was 73 +/- 13
      microliters/min in the middle-aged subjects and was not significantly different
      from the value measured in young subjects (80 +/- 12 microliters/min). Retinal
      perfusion pressure was significantly higher in the older subjects, primarily due
      to elevated systemic BP. The similarity in total flow between the two groups,
      even though the retinal perfusion pressures were higher in the older group, is an
      indication of an increased vascular resistance to flow. The increase may be an
      aging phenomenon or an indication of a well-functioning autoregulatory capacity
      in the retinal vasculature of the older subjects.

PMID- 9032793
TI  - Effects of topically applied prostaglandin F2 alpha on normotensive human eyes.
AB  - The ocular effects of topical prostaglandin F2 alpha (PGF2 alpha) were studied in
      normotensive human eyes. PGF2 alpha as tromethamine salt, 100 micrograms, was
      applied to one eye of 23 normotensive subjects, intraocular pressure (IOP) and
      pupil size were measured, objective and subjective findings recorded during the
      first 24 h. Tonography was performed in 10 subjects. As compared with the
      baseline, PGF2 alpha caused a significant IOP reduction between 1 and 24 h (p <
      0.001), being maximal (4.9 +/- 0.5 mm Hg, mean +/- SEM, p < 0.001) between 4 and
      8 h. As compared with the contralateral control eyes, which received 50
      microliters of saline, treated eyes exhibited significant IOP reduction between 1
      and 24 h (p < 0.001), being maximal (4.2 +/- 0.4 mm Hg, mean +/- SEM, p < 0.001)
      at 4 h. PGF2 alpha caused marked conjunctival hyperemia in all eyes. Pupillary
      diameter was not altered. Aqueous flare and cellular response were not seen. Half
      of the subjects complained of ocular smarting, mild ocular pain or headache.
      Total outflow facility did not change (p > 0.05).

PMID- 9032794
TI  - Angiogenin levels in the vitreous from patients with proliferative diabetic
      retinopathy.
AB  - The vitreous levels of angiogenin, which is a potent blood vessel-inducing
      protein, were measured to determine their association with proliferative diabetic
      retinopathy (PDR). Undiluted vitreous fluid specimens were collected from 30 eyes
      with PDR at the time of vitrectomy. A sandwich enzyme-liked immunosorbent assay
      was then used to quantitate the levels of angiogenin. As a control we determined
      the levels in the specimens from 21 patients with proliferative vitreoretinopathy
      (PVR) and 4 patients with idiopathic macular epiretinal membrane (IERM). The
      average angiogenin level in the eyes with PDR was 43.7 ng/ml, and no significant
      difference was observed among PDR, PVR and their reoperation cases. In the
      category of IERM, the mean concentration of angiogenin was 2.1 ng/ml, which was
      significantly lower than that of the PDR and PVR cases. Our study thus
      demonstrated a significant increase in the vitreous angiogenin levels in eyes
      with PDR, PVR and those undergoing reoperation for these conditions in comparison
      to eyes with IERM. We therefore postulated that the elevated angiogenin levels
      thus reflected a breakdown of the blood-ocular barrier in eyes with PDR and PVR.

PMID- 9032795
TI  - Growth factors and their receptors in the anterior chamber. Absence of epidermal
      growth factor and transforming growth factor alpha in human aqueous humor.
AB  - The involvement of growth factors such as epidermal growth factor (EGF) in
      regenerative processes of corneal endothelium and lens epithelium has recently
      been suggested. However, knowledge on the presence of growth factors in anterior
      chamber fluid (ACF) is still very restricted. Although we have previously shown
      that EGF is undetectable in the ACF of normal eyes undergoing cataract surgery
      even by the use of high-sensitivity assays, this does not exclude the possible
      presence of other, EGF-like proteins in ACF such as transforming growth factor
      alpha (TGF-alpha). In the present study, we have hence determined in ACF samples
      of 70 human eyes the concentrations of both EGF and TGF-alpha. As assays served
      ELISA techniques and RIA. In none of all the samples investigated could
      detectable amounts of EGF, i.e. above 0.2 pg/ml (detection limit of the assay),
      be found, confirming earlier results. Interestingly, however, also no TGF-alpha
      could be detected in ACF. If present at all, the level of any TGF-alpha
      concentration in ACF was hence below the detection limit, i.e. less than 20
      pg/ml. Based on the results of this study, it seems therefore that under
      physiological conditions there is no measurable presence of free EGF or TGF-alpha
      in human ACF. Existing receptors in the structures of the anterior segment must
      hence have ample binding capacity which could explain the effect of externally
      applied growth factors. The physiological and clinical importance of this result
      is briefly outlined.

PMID- 9032796
TI  - Isoelectric focusing of crystallins in microsections of calf and adult bovine
      lens. Identification of water-insoluble crystallins complexing under
      nondenaturing conditions: demonstration of chaperone activity of alpha
      crystallin.
AB  - Topographic studies of crystallin fractions from the young adult bovine lens
      revealed that lenses do not have a homogeneous distribution of crystallins. There
      are, however, gradual differences between the cortices and the nucleus. The
      isolated lenses were separated mechanically into lens equator and inner cylinder.
      The latter was then sectioned in a special sectioning machine into 11-12
      morphological layers (from anterior cortex through nucleus to posterior cortex).
      Matters of the lens sections were separated into water-soluble (WS) and water
      insoluble (WI) crystallins. The WI fractions were solubilized with 100%
      formamide, or dissolved into 7 M urea. Crystallin profiles were obtained for each
      lens layer, using thin-layer isoelectric focusing in polyacrylamide gel. WS
      crystallins from the lens equator revealed a separation into HM-, alpha L-, beta
      H-, beta L-, beta S- and gamma-crystallins. The WI fractions of the layers
      dissolved in urea gave a separation into the individual HM- (3 components), alpha
      L- (4 components), beta- (6 component groups), beta S- (2 components) and gamma-
      (11 components) crystallins in the different morphological layers. The results
      confirm that a significant age-related increase in several beta- and gamma
      crystallins incorporated into alpha-crystallins exists in the patterns of WI
      fractions of the different layers from lenses of 2.2 and 5.9 years. The WI
      crystallins solubilized in formamide showed only the presence of HM weight and
      alpha-crystallin moieties, due to the action of chaperone activity of alpha
      crystallin. The nature of the WI protein fraction in the separated lens layers
      reflected to the aggregated state of: alpha L-, beta L-, beta S- and gamma
      crystallins in the different regions of the lens, concealed in the central cavity
      of the alpha-crystallin chaperone model.

PMID- 9032797
TI  - Effects of a nitric oxide donor and nitric oxide synthase inhibitors on acid
      secretion of isolated rabbit gastric glands.
AB  - The present study aims to investigate the effect of nitric oxide (NO) on
      histamine-stimulated acid secretion of gastric glands. An NO donor, sodium
      nitroprusside (SNP), and inhibitors of NO synthase such as NG-nitro-L-arginine
      methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA) with or without L-arginine,
      a substrate for NO synthase, were added to isolated rabbit gastric glands with
      the secretagogues. Acid secretion, intracellular concentrations of cGMP and cAMP
      and lactic dehydrogenase (LDH) release were determined. L-NAME and L-NNA
      increased stimulated acid secretion, which was reversed by L-arginine. SNP
      inhibited stimulated acid secretion concentration-dependently; the inhibition was
      accompanied by an increase in the intracellular cGMP, but neither related to cAMP
      nor LDH release. In conclusion, NO produced in large quantity by an NO donor
      inhibits histamine-stimulated acid secretion of isolated rabbit gastric glands.

PMID- 9032798
TI  - Peripheral effects of opioids in a model of intestinal inflammation in mice.
AB  - The study evaluates the peripheral component of the antitransit effects of
      opioids during acute intestinal inflammation induced by the intragastric
      administration of croton oil (CO) in mice. Gastrointestinal transit was measured
      3 h after CO or saline (SS) administration with a charcoal meal. In both groups,
      the effects of mixed (morphine, fentanyl, U-50488H) and peripherally acting (N
      methylmorphine, PL017, ICI-204448) opioids and their antagonism by naloxone and
      naloxone methiodide were established. During inflammation, the potencies of
      morphine and N-methylmorphine increased 3 times, and those of fentanyl and PL017,
      1.9 times. The effects were reversed by naloxone (0.1 mg/kg) and naloxone
      methiodide (0.3 mg/kg). No dose-response relationships could be elicited with U
      50488H or ICI-204448, and their antitransit effects were analogous in SS- and CO
      treated animals. These results show that during inflammation the enhanced
      antitransit effects of opioids are primarily mediated by interaction with opioid
      receptors located at peripheral sites. In addition, inflammation of the gut seems
      to induce a sensitization of mu-but not kappa-opioid receptors.

PMID- 9032799
TI  - Effects of ergotamine and dihydroergotamine on 5-hydroxytryptamine-2A receptors
      in the isolated rat aorta.
AB  - Ergotamine contracted isolated rat aorta rings with an intrinsic activity of 50%
      of that of 5-hydroxytryptamine. (5-HT, 0.1 mmol/l). Dihydroergotamine did not
      contract the tissue, but insurmountably blocked contraction in response to
      ergotamine and 5-HT. The 5-HT2A receptor antagonist, ketanserin (0.1 mumol/l),
      inhibited ergotamine (pKB 8.0) and 5-HT (pKB 8.1) induced contractions. These
      results indicate that in the rat aorta ergotamine is a partial 5-HT2A receptor
      agonist, whilst dihydroergotamine is an insurmountable 5-HT2A receptor
      antagonist. The present data could explain why ergotamine displays more
      cardiovascular and uterotonic side effects than dihydroergotamine.

PMID- 9032800
TI  - Effects of selective and nonselective alpha-1-adrenoceptor antagonists on
      intraurethral and arterial pressures in intact conscious dogs.
AB  - In this study, we used a novel conscious dog model to evaluate the uroselectivity
      of selected alpha 1-antagonists either approved for human use or in clinical
      development for the treatment of symptomatic benign prostatic hyperplasia (BPH)
      and compared those results to their in vitro binding and functional affinities at
      alpha 1A, alpha 1B and alpha 1D receptor subtypes. Conscious dogs were
      instrumented acutely with a balloon catheter for the measurement of changes in
      prostatic intraurethral pressure (IUP) and chronically with implantable telemetry
      devices for the measurement of arterial pressure. The pressor effects of the
      alpha 1-agonist phenylephrine (PE) on IUP and mean arterial pressure (MAP) were
      compared before and at various time points after oral doses of either terazosin,
      doxazosin, tamsulosin or Rec 15/2739 (SB 216469). At submaximal doses, terazosin
      and doxazosin blocked PE-induced increases in MAP to a greater extent than
      increases in IUP. Tamsulosin blocked both parameters equally at the lowest and
      highest doses; however, at the intermediate dose, IUP was blocked more than MAP.
      Rec 15/2739 at each dose always blocked IUP to a greater extent than MAP. While
      the in vivo uroselectivity of these agents was predicted by radioligand binding
      and in vitro functional selectivity for the alpha 1A subtype over alpha 1B and
      alpha 1D subtypes, results from conscious dog experiments indicate that estimates
      of in vivo uroselectivity also depend upon dose and the time after
      administration. Our conscious canine model provides the basis for frequent and
      repeated evaluation of uroselectivity parameters over many hours, thus providing
      a pharmacological profile of compound effects perhaps more relevant to clinical
      practice.

PMID- 9032801
TI  - Inhibitory effects of centrally administered somatostatin on the adrenal zona
      glomerulosa in male rats.
AB  - This study examined the effects of intracerebroventricularly administered
      somatostatin (SRIF-28 and SRIF-14) on growth and steroidogenic capacity of the
      rat adrenal zona glomerulosa. Male adult Wistar rats were subjected to
      intracerebroventricular administration of three 1 microgram doses of SRIF-28 or
      SRIF-14 every other day. Five days after the last dose, the rats were sacrificed
      by decapitation. Blood samples were collected for hormonal analyses, and left
      adrenal glands were taken for histological and morphometric evaluation. In
      comparison with control animals, the SRIF-treated rats had decreased (p < 0.05)
      adrenal gland weight and volume. Stereological and morphometric analyses showed
      decreased (p < 0.05) absolute and relative volumes of the cells and nuclei only
      in the zona glomerulosa. The plasma levels of aldosterone, growth hormone, and
      prolactin in both SRIF-treated groups were lower (p < 0.05) than in the control
      group. The levels of adrenocorticotropic hormone after SRIF treatment did not
      differ significantly from those in control rats. These findings suggest that
      centrally administered somatostatin is specifically involved in the control of
      zona glomerulosa growth and secretion; this effect is probably mediated by
      inhibiting the secretion of the corresponding pituitary hormones.

PMID- 9032802
TI  - Effects of the diacylglycerol kinase inhibitor, R59022, on TSH-stimulated iodide
      organification in porcine thyroid cells.
AB  - We and others have demonstrated that protein kinase C (PKC) activators such as
      the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibit
      differentiated thyroid function in vitro. However, phorbol-mediated PKC
      activation differs from that induced by analogues of the endogenous PKC
      activator, diacylglycerol (DAG). To explore the effects of endogenous PKC
      activation on differentiated thyroid function, we examined the effects of the DAG
      kinase inhibitor, R59022, on TSH-mediated iodide organification in porcine
      thyroid cells. Following incubation of the thyroid cells for 30 min, 20 and 50
      mumol/l R59022 inhibited TSH-stimulated iodide organification by 20 and 41%,
      respectively. Prolonged exposure (36 h) to R59022 was also studied since similar
      treatment with TPA downregulates PKC activity. Inhibition of TSH-mediated iodide
      organification was observed with as little as 5 mumol/l R59022 (56% of control, p
      < 0.01) with maximal inhibition using 50 mumol/l R59022 to 13% of control values
      (p < 0.001). To demonstrate that these effects were mediated by PKC activation,
      PKC isoforms were measured by Western blotting following R59022 exposure (50
      mumol/l, 30 min). Increased membrane-bound alpha- and zeta-PKC isozymes were
      observed. This is the first demonstration linking specific PKC isoforms to
      changes in differentiated thyroid function in vitro. The present data suggest
      that alpha- and/or zeta-PKC mediate the effects of R59022 on differentiated
      thyroid function in vitro. Further, a PKC inhibitor, chelerythrine (1 mumol/l)
      was able to partially reverse the effects of prolonged R59022 exposure on TSH
      mediated iodide organification. These studies demonstrate that R59022 exposure
      inhibits TSH-mediated iodide organification in porcine thyroid cells and that
      these effects are mediated via endogenous PKC activation. These data are
      consistent with the concept that endogenous PKC acts as a negative modulator of
      differentiated thyroid function in the porcine thyroid cell.

PMID- 9032803
TI  - Relation between theophylline and circulating vitamin levels in children with
      asthma.
AB  - We investigated the effect of theophylline administration on circulating vitamin
      levels in children with asthma. Twenty-three asthmatic children, ranging in age
      from 7 to 15 with a mean of 10.8 years and including 16 patients who were treated
      with slow-release theophylline and 7 patients not receiving any type of
      theophylline preparation, were enrolled in this study. They all were inpatients
      who had been hospitalized for the control of asthma. Steady-state serum
      theophylline and vitamin A, B1, B2, B6, B12 and C levels were evaluated in these
      patients. Circulating vitamin B1 and B6 levels were depressed in asthmatic
      children treated with theophylline compared to those not receiving the agent
      (38.4 +/- 1.6 (mean +/- SEM) vs. 46.4 +/- 3.5 ng/ml and 7.1 +/- 0.5 vs. 11.8 +/-
      2.1 ng/ml, respectively, p < 0.05). A significant negative correlation between
      theophylline and circulating levels of vitamin B6 was demonstrated in the
      subjects of this study (rs = -0.657, p < 0.001). In contrast, no relationship was
      noted between theophylline and circulating vitamin B1 levels. Theophylline did
      not affect circulating vitamin A, B2, B12 or C levels. We conclude that
      theophylline induces depression of circulating vitamin B1 and B6 levels in
      asthmatic children, although a dose-dependent interaction between theophylline
      and vitamin B1 would be unlikely.

PMID- 9032804
TI  - Inhibin, activin and follistatin in the human placenta--a new family of
      regulatory proteins.
AB  - The family of inhibin-related proteins has been investigated extensively in the
      last decade. It is composed of three members: inhibin, activin and follistatin.
      Inhibin and activin are chemically related, while follistatin acts as an activin
      binding protein. Initially identified as regulators of pituitary follice
      stimulating hormone (FSH) secretion, inhibin, activin and follistatin have more
      recently been characterized as growth factors, embryo modulators and immune
      factors. Human placenta, amnion, chorion and maternal decidua express mRNAs for
      inhibin, activin and follistatin, and the presence of both immunoreactive and
      bioactive proteins has been demonstrated. The proteins are present in maternal
      and fetal circulation, and are measurable in amniotic fluid with changes related
      to gestational age and to the occurrence of gestational diseases. Various
      biological actions have been described in embryo and intrauterine tissues, which
      suggest a role for these proteins in the development of the gestational unit.
      However, several questions remain to be elucidated. The chemical forms of
      inhibin, activin and follistatin produced by human placenta and the mechanisms
      involved in the regulation of their secretion are largely unknown. The nature of
      the receptors for these proteins and the physiological implications of receptor
      activation have not yet been elucidated and this will require further
      investigation.

PMID- 9032805
TI  - Differential expression of G1 cyclins during human placentogenesis.
AB  - Cyclins are proteins that support the progression of cell-cycle stages in
      proliferating cells. The purpose of this study was to determine which of the
      cyclin genes is involved in the regulation of normal human trophoblast
      proliferation. The presence and cellular localization of four G1 cyclins D1, D2,
      D3 and E, were determined by immunohistochemistry. This analysis indicated that
      cyclins E and D3 are the predominant cyclins in villous trophoblast. D2 was
      present only within the villous core, in fetal macrophages. Positive
      immunoreactivity for cyclin D1 was strongest in second and third trimester
      placentae, in the cells lining the intravillous vessels with additional
      reactivity in extravillous cytotrophoblasts. Because cyclin E protein was present
      in a greater percentage of cells than those that are dividing, Western blot
      analysis was performed to validate the fidelity of the immunohistochemistry data.
      The results of the Western analysis revealed that two forms of cyclin E protein
      of the appropriate size were present. Data collected from this study suggest that
      within the trophoblast lineage, cyclins D3 and E are important cell cycle
      regulatory proteins, and further, that cyclin E may function in trophoblast
      terminal differentiation as well.

PMID- 9032806
TI  - Relative expression of epidermal growth factor receptor in placental
      cytotrophoblasts and choriocarcinoma cell lines.
AB  - The role of transforming growth factor-alpha (TGF-alpha)-epidermal growth factor
      receptor (EGFR) interactions in regulating benign and malignant trophoblast
      proliferation were examined. Benign cytotrophoblast (CT) demonstrated mitogenic
      stimulation in response to TGF-alpha; BeWo and JAr choriocarcinoma cell lines
      failed to respond. EGFR levels in BeWo and JAr were determined by enzyme linked
      immunoassay (ELISA) to be at least 10-fold higher than those in benign CT. EGFR
      isolated from BeWo and JAr also demonstrated functional tyrosine kinase activity.
      Using a combination of immunoperoxidase (IP) and ELISA techniques,
      choriocarcinoma cells were found to produce significant quantities of TGF-alpha
      that were comparable with those reported previously by this laboratory for benign
      CT, and were felt to be stimulating their own proliferation in an autocrine
      fashion. EGFR blocking and TGF-alpha neutralizing antibodies inhibited JAr
      proliferation whereas an EGF neutralizing antibody did not. The data presented
      here and in our previous report indicate that a TGF-alpha-EGFR autocrine loop may
      regulate normal and malignant CT proliferation. Choriocarcinoma cells may be
      proliferating at a maximal rate due, in part, to EGFR overexpression and are
      therefore unable to respond further to exogenous growth factor. Thus, EGFR
      overexpression may contribute to the uncontrolled proliferation of
      choriocarcinoma cells in general.

PMID- 9032807
TI  - Purification and properties of placental prolactin-related protein-I.
AB  - We used sucrose density gradient centrifugation, size exclusion chromatography,
      and high-pressure reversed-phase chromatography in the purification of bovine
      prolactin-related protein-I (bPRP-I) to homogeneity from a secretory granule
      enriched fraction of fetal cotyledon. Amino terminal sequence was unambiguous,
      consistent with the nucleic acid sequence of the cDNA 50 codons distal to the
      initial AUG in the open reading frame, and began with the residues:
      RKSFTDRFMNAASLSHDFY. This is distinct from the signal peptide cleavage site
      predicted by the algorithm of von Heijne (1986) as well as that expected by
      comparison with other members of the growth hormone/prolactin family of hormones.
      The level of bPRP-I in uterine fluid was sufficient to detect by Western blot of
      unfractionated material and estimated as at least 0.65 microM. In contrast, bPRP
      I was undetectable in the serum by this method. Interaction of [125I]-bPRP-I with
      high molecular weight serum components interfered with its measurement by radio
      immunoassay, and could be replicated with purified alpha 2-macroglobulin with an
      apparent KD of about 0.41 microM. Thus, the bPRP-I gene product is processed
      secreted and distributed in a manner consistent with a paracrine action at the
      materno-fetal interface.

PMID- 9032808
TI  - Intrahepatic cholestasis of pregnancy impairs the activities of human placental
      xenobiotic and steroid metabolizing enzymes in vitro.
AB  - Human placental xenobiotic metabolizing and aromatase activities were measured in
      placentae at term obtained from pregnancies diagnosed as intrahepatic cholestasis
      (IC). Compared with controls, several cytochrome P450-dependent (CYP) mono
      oxygenases were significantly decreased in IC placentae: 7-ethoxycoumarin O
      deethylase by 75 per cent, 7-ethoxyresorufin O-deethylase by 95 per cent,
      aromatase activity by 37 per cent and androstenedione formation, using
      testosterone as a substrate, by 20 per cent. These results demonstrate that
      maternal intrahepatic cholestasis effectively decreases CYP dependent metabolism
      in human placenta in vitro which may pose a potential risk to the wellbeing of
      the fetus. Because aromatase activity in IC placentae is significantly lower as
      compared with healthy controls, safety of the drug therapies which further
      inhibit aromatase activity are questioned.

PMID- 9032809
TI  - Term ovine placental vasculature: comparison of sea level and high altitude
      conditions by corrosion cast and histomorphometry.
AB  - The placental vascular architecture differs significantly at high altitude from
      that at sea level in the human and guinea-pig. Four sheep between 137 and 140
      days of gestation, kept near sea level throughout gestation, were used as a
      normoxic control group for comparison of the placental vasculature with 10 other
      ewes, kept at high altitude (3820 m above sea level; Barcroft Laboratory, White
      Mountain Research Station, CA, USA). Placentomes from both groups were prepared
      for histology and scanning electron microscopy of vascular corrosion casts.
      Singular perfusion of fetal placentae, as well as combined maternal/fetal
      injection was performed. The influence of long-term hypoxaemia was determined by
      qualitative and semi-quantitative evaluation of corrosion casts and histological
      sections. The fetal vessel casts show a distinct difference in the arrangement of
      vessels of all sizes in response to long-term hypoxaemia. In the control group,
      stem arteries and veins are straight and parallel. In contrast, this is much less
      evident in the hypoxaemic group because arterioles and venules branch off the
      stem vessels more frequently and in an irregular manner. This leads to a
      capillary bed that is much more dense due to increased branching and capillary
      coiling. These observations are confirmed by histomorphometry. In the fetal
      vessels of high altitude sheep placentomes, we observed a decreased number of
      vascular cross sections (21.6 +/- 4.7 SEM versus 27.7 +/- 4.0 SEM; P = 0.02).
      However, the average luminal size per cross section (77.9 +/- 10.5 microns2 SEM
      versus 59.4 +/- 7.4 microns2 SEM; P = 0.004) was increased at high altitude and
      the percentage of lumina of the total area (5.7 +/- 0.5 SEM versus 5.3 +/- 0.3
      SEM; P = 0.09) indicated a trend towards an increase. In maternal vessels of high
      altitude placentomes, the number of vessel cross sections (6.5 +/- 0.7 SEM versus
      6.0 +/- 0.5 SEM; P = 0.2) remained unchanged, whereas the average luminal size
      (1108 +/- 122 microns2 SEM versus 844 +/- 77 microns2 SEM; P < 0.001) and the
      percentage of lumina out of the total area (20.9 +/- 1.8 SEM versus 17.5 +/- 1.7
      SEM; P < 0.001) were increased. The interhaemal distance appeared to be slightly
      but not significantly increased at high altitude. These findings indicate that at
      high altitude the sheep placenta develops an increased materno-fetal absorptive
      surface to help guarantee substance exchange.

PMID- 9032810
TI  - Stromal differentiation and architecture of the human umbilical cord.
AB  - In order to assess the characteristics of its stromal cells and the distribution
      of extracellular matrix proteins, we investigated, immunohistochemically and
      ultrastructurally, term, first and second trimester human umbilical cords. A
      differential distribution pattern of the various cytoskeletal proteins of stromal
      cells and extracellular matrix proteins was observed in different zones of the
      stroma, the subamniotic stroma, Wharton's jelly, and the vessels' adventitia. All
      three zones showed immunoreactivities for collagen types I, III and VI and for
      basement membrane molecules such as collagen type IV, laminin and heparan
      sulphate proteoglycan. Immunoreactivities for these extracellular matrix
      molecules were observed around cleft-like territories (stromal clefts) in the
      Wharton's jelly which were occupied by homogeneous ground substance but void of
      collagen fibrils and basal lamina molecules. Moreover, between the stromal
      clefts, slender cells were found which immunohistochemically and
      ultrastructurally corresponded to various stages of myofibroblastic
      differentiation. In earlier stages of gestation, stromal cells with a less
      complex expression pattern prevailed. The stromal clefts and the contractile
      cells together might serve as a system regulating the turgor of the cord.

PMID- 9032811
TI  - Placental norepinephrine transporter development in the ovine fetus.
AB  - The placenta has been shown to be a site of expression of several of the
      monoamine membrane uptake transporters. However, the development and relative
      contribution of transport-dependent mechanisms to placental catecholamine
      clearance in vivo have not been demonstrated. These studies were designed to
      determine the development of the placental norepinephrine transporter (NET) and
      the relative contribution of transport dependent mechanisms to whole body and
      placental catecholamine clearance. Norepinephrine clearance and production rate
      were determined in 122 +/- 1 day gestation chronically catheterized fetal sheep.
      Placental clearance was shown to account for over 40 per cent of total
      intrauterine clearance and, of the clearance in the placenta, nearly 50 per cent
      was uptake, transport-dependent as shown by specific pharmacologic blockade. NET
      transport expression was examined by measurement nisoxetine binding in placenta
      and compared with binding in the frontal cortex of fetal, newborn and adult
      animals. Nisoxetine is a selective ligand for the norepinephrine transporter.
      Nisoxetine binding was 20-fold greater in placenta than in frontal cortex.
      Placental transporter binding decreased modestly in between 99 days gestation and
      term (145 days) but did not change in frontal cortex. These results suggest that
      expression of the norepinephrine transporter in the placenta is associated with a
      significant capacity for neurotransmitter re-uptake in utero. Given the high
      fetal norepinephrine production rate, this capacity is important for fetal
      homeostasis. This site of transporter expression may be important in the
      pathogenesis of derangements in catecholamine production in the fetus and in the
      adverse effects on the fetus of drugs, such as cocaine, which block catecholamine
      re-uptake.

PMID- 9032812
TI  - Binding of human isotransferrin variants to microvillous and basal membrane
      vesicles from human term placenta.
AB  - Transferrin (Tf)-dependent iron transfer from mother to fetus is mediated by Tf
      receptors (TfRs) which are present on both microvillous and basal membranes of
      human placental syncytiotrophoblast. We used microvillous and basal membrane
      vesicles, both isolated from the same human term placenta, to investigate the
      binding of [125I]-labelled diferric bi-bi antennary tetra-sialo Tf (bb Tf), bi
      tri-antennary penta-sialo Tf (bt Tf) and tri-tri-antennary hexa-sialo Tf (tt Tf).
      To diminish the effect of endogenous Tf, membrane vesicles were washed before
      binding of [125I]-Tf. The number of TfRs on microvillous membranes was 6.1 +/-
      2.4 (mean +/- s.d., n = 15) times higher than that on basal membranes, whereas
      the affinity of TfRs on basal membranes was 3.9 +/- 0.4 (mean +/- s.d., n = 15)
      times higher than that of TfRs on microvillous membranes, irrespective the isoTf
      used. The affinity constants of TfRs on both microvillous and basal membranes
      were higher for bb Tf than for bt Tf and higher for bt Tf than for tt Tf.
      However, these latter differences were rather small and probably not of
      physiological importance.

PMID- 9032813
TI  - Leucine sources for the rat fetus.
AB  - Fetal and maternal plasma were assayed for the concentration of free leucine,
      acid-insoluble radioactivity and acid-soluble radioactivity at intervals after an
      intravenous bolus injection of [3H]leucine into anaesthetized pregnant rats at
      17.5 days post-conception. The concentrations of total free leucine and of free
      [3H]leucine in maternal and fetal plasma were effectively unchanged from 5 to 180
      min post-injection. Plasma free leucine concentrations in the fetus were five
      times those in the mother. The concentration of free [3H]leucine in fetal plasma
      was similar to that in maternal plasma. Thus the specific radioactivity of free
      leucine in fetal plasma is substantially lower than that in maternal plasma,
      indicating that a significant portion of the free leucine in plasma of the 17.5
      day rat fetus comes from a source other than the free leucine in the maternal
      plasma. The data are consistent with a major contribution of amino acids coming
      from the degradation of extraembryonic protein in the yolk sac. Other possible
      sources of unlabelled leucine are discussed.

PMID- 9032814
TI  - When is the maternal placental circulation established in man? 1941.

PMID- 9032815
TI  - Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients
      with muscle tension and fibromyalgia.
AB  - Muscle tissue oxygen tension was measured by a polarographic oxygen fine-needle
      probe, and inorganic phosphate and creatine phosphate spectra were recorded using
      magnetic resonance spectroscopy in patients with chronic low back pain and in
      patients with fibromyalgia. Results were compared with healthy controls. The
      tissue oxygen tension was markedly higher in those with tense muscles than in
      normal subjects. Magnetic resonance spectra for inorganic phosphate were higher
      in patients demonstrating muscle contraction, and intracellular pH was shifted in
      the alkaline direction in cases with increased muscle tension. Results show that
      hypoxia is not the result of increased muscle tension, as was thought previously,
      but results from oversupply of oxygen demanded by the muscle, leading to
      increased capillary perfusion and rising oxygen tension.

PMID- 9032817
TI  - Correlation between anti-Proteus antibodies and isolation rates of P. mirabilis
      in rheumatoid arthritis.
AB  - In a survey of 89 RA patients, carried out under code, Proteus mirabilis was
      isolated from the urine of 63% (47/75) of female (P < 0.001) and 50% (7/14) of
      male patients (P < 0.001), compared to a frequency of isolation in healthy women
      of 32% (38/119) and 11% (13/115) in healthy men. There was no significant
      difference in isolation rates between 37 non-RA patients and healthy controls.
      Sera from 20 patients with RA and 20 healthy controls were tested against P.
      mirabilis and Escherichia coli by an enzyme-linked immunosorbent assay.
      Antibodies against P. mirabilis but not to E. coli were significantly higher in
      the RA patients than in healthy controls (P < 0.001). Furthermore, a positive
      correlation was found between high anti-Proteus antibody levels in serum samples
      and the number of Proteus colony-forming units obtained from urine specimens of
      the 20 RA patients (r = +0.714, P < 0.001). These results support the suggestion
      of an aetiopathogenic role for P. mirabilis in RA.

PMID- 9032816
TI  - Serum levels of soluble CD44 variant isoforms are elevated in rheumatoid
      arthritis.
AB  - Serum levels of soluble CD44 variant proteins including sequences encoded by exon
      v5 and exon v6 (sCD44v5, sCD44v6) were determined in patients with inflammatory
      rheumatic diseases: 56 with rheumatoid arthritis (RA+) and 31 with miscellaneous
      inflammatory rheumatic diseases (MIRD). There were very significantly higher
      serum levels of sCD44v5 and sCD44v6 in patients with RA+ than in those with MIRD
      (RA+ to MIRD: sCD44v5: 81 +/- 54 ng/ml to 33 +/- 13 ng/ml; sCD44v6: 237 +/- 124
      ng/ml to 166 +/- 53 ng/ml; both P << 0.001). In RA+ elevated serum levels of
      sCD44v5 were correlated with the inflammatory activity of disease. In 17 patients
      with RA+ three or four follow-up measurements of sCD44v5 were performed within 6
      months. The development of sCD44v5 serum levels reflected the clinical course of
      disease in the patients investigated.

PMID- 9032818
TI  - Evaluation of synovial cytokine patterns in rheumatoid arthritis and
      osteoarthritis by quantitative reverse transcription polymerase chain reaction.
AB  - To compare the cytokine profile with the degree and composition of cellular
      infiltration in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium,
      synovial membranes from patients with RA (n = 14) and OA (n = 5) were examined,
      employing immunohistochemistry and competitive reverse-transcriptase polymerase
      chain reaction (RT-PCR), for interleukin (IL)-I beta, IL-2, IL-4, IL-5, IL-6, and
      IL-10, and tumour necrosis factor-alpha (TNF-alpha) gene expression. It was found
      that the strength of cytokine gene expression within the synovial membranes of
      patients with RA was not significantly correlated with the degree of synovial
      infiltration of T-cells, B-cells, or macrophages. No IL-2, IL-4, or IL-5 RNA was
      detected in the synovium of either RA or OA. Quantitative cytokine determination
      showed a similar pattern in RA and OA, although the two diseases differed in
      total synovial infiltration and the composition of infiltrating cellular
      elements. Thus the number of cell types known to produce certain cytokines does
      not appear to determine the strength of synovial cytokine expression measured by
      quantitative RT-PCR. Furthermore, the pattern of T-cell specific cytokines found
      in RA synovium does not accord with the concept of the TH0, TH1, and TH2.

PMID- 9032819
TI  - Quantification of mRNA levels in joint capsule and articular cartilage of the
      murine knee joint by RT-PCR: kinetics of stromelysin and IL-1 mRNA levels during
      arthritis.
AB  - We developed a method to isolate well defined joint specimens from different
      compartments of normal and arthritic murine knee joints in which mRNA levels of
      stromelysin and IL-1 were semiquantified using RT-PCR. Joint capsule specimens
      were isolated on medial and lateral sides of the patella with a biopsy punch.
      Cartilage layers were isolated from patellae after a mild decalcification with
      EDTA. EDTA treatment had no effect on the amount and efficiency of amplification
      of mRNA when tested on isolated chondrocytes. After induction of experimental
      arthritis, stromelysin mRNA was elevated approximately 50 times in both joint
      capsule and cartilage. IL-1 was elevated 100 times in joint capsule but only 10
      times in cartilage. Kinetic analysis of mRNA levels in cartilage during arthritis
      showed a prolonged elevation of stromelysin mRNA compared to IL-1. The variation
      in mRNA levels between joints of individual mice proved to be low, showing that
      sampling of the specimens and subsequent RT-PCR can be performed reliably. The
      current method offers a valuable approach to study gene expression in knee joints
      during murine experimental arthritis.

PMID- 9032820
TI  - Stimulation of whole blood cultures in patients with ankylosing spondylitis by a
      mitogen derived from Mycoplasma arthritidis (MAS) and other mitogens.
AB  - In this study we compared cytokine production and cell proliferation of
      immunocompetent cells derived from patients with ankylosing spondylitis (AS) to
      those from healthy blood donors using a whole blood assay. To this end, blood
      cell cultures were stimulated with the superantigens MAS (Mycoplasma arthritidis
      supernatant) and staphylococcal enterotoxin B (SEB) and the plant lectins
      phytohaemagglutinin (PHA) and concanavalin A (Con A). The number of white blood
      cells (WBC) and lymphocyte subsets were also determined. Cell proliferation and
      levels of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta) and
      interleukin-6 (IL-6) were measured after stimulation with the different mitogens.
      An ELISA test was used to analyse supernatant cytokine levels. Individuals with
      AS showed significantly lower IFN-gamma concentrations and markedly lower cell
      proliferation rates with all tested mitogens than healthy controls, while there
      was no significant difference in IL-6 synthesis. IL-1 beta levels were slightly
      impaired in the patient group, but only blood cell cultures stimulates with MAS
      showed a statistical significance. Furthermore, there was a significant elevation
      of leucocytes and lymphocytes in patients with AS resulting in higher numbers of
      CD4-positive cells, which implies a higher CD4:CD8 cell ratio. CD19- and CD8
      positive cells were not significantly distinct compared to healthy controls. This
      deviation in cytokine levels and cell proliferation points to a suppression of T
      lymphocytes. A disturbed T-lymphocyte function may play a part in the
      pathogenesis of AS.

PMID- 9032821
TI  - Lupus vulgaris in a patient with systemic lupus erythematosus and persistent IgG
      deficiency.
AB  - We present the case of a patient with juvenile onset systemic lupus erythematosus
      (SLE) who developed a persistent, acquired hypogammaglobulinaemia with IgG
      deficiency. The hypogammaglobulinaemia was probably a complication of high dose
      corticosteroid treatment. The serum IgG level remained subnormal despite
      intravenous immunoglobulin therapy. Lupus vulgaris, which developed on the nasal
      cartilage in this patient with SLE, is not an expected finding. This patient is
      probably the first reported case of SLE associated with lupus vulgaris.

PMID- 9032822
TI  - Systemic lupus erythematosus arising in a patient with chronic silicosis.

PMID- 9032823
TI  - Beliefs on coping with illness: a consumer's perspective.
AB  - This article discusses the results of a study on beliefs on coping with illness
      and coping with the health care system. Using the concept mapping method, members
      of patient organizations (n = 172) sorted their beliefs on coping with illness
      and coping with the health care system into two dimensions (priority and
      content). Statistical analysis reveals eight beliefs on coping with illness, with
      "autonomy" and "acceptance of illness" as the most important. It also reveals
      eight beliefs on coping with the health care system, of which the most important
      is a professional relationship with the physician based on mutual trust and
      respect between two equal partners. It is argued that these beliefs represent
      idealized images of coping with illness and coping with the health care system.
      In relation to the political debate on responsible use of the health care system
      in Western countries, these findings show many patients are willing to act as
      responsible consumers of health care, that is, if providers of health care create
      an environment in which patients receive guidance in determining alternatives.

PMID- 9032824
TI  - Shattered assumptions: time and the experience of long-term HIV positivity.
AB  - This paper elucidates one of the main existential problems faced by people living
      with an HIV positive diagnosis-the disruption in their routine orientation
      towards time and the way in which this has the capacity to affect their lives
      more generally. Drawing upon research with people who have been living with an
      HIV positive diagnosis for at least five years, the paper aims to illuminate the
      "provisional existence" imposed upon the individual by the diagnosis and suggests
      that this ambiguous position underpins the many psychological and social problems
      confronted by them. In addition, however, the paper argues that in order for the
      individual to adjust effectively to living with an HIV positive diagnosis, it is
      necessary for him/her to develop alternative ways of conceiving and living within
      time, which "compensates" for the loss of the temporal assumptions that existed
      prior to diagnosis. The various ways in which individuals manage to do this are
      documented in this paper, as is the failure to do so and the psychosocial
      consequences ensuing from this. It is further argued that the ability to achieve
      compensatory temporal understanding is related to the individual's more general
      "existential orientational framework", of which temporal perspective is a
      constituent component. Finally, the implications of such findings are discussed
      for the targeting of appropriate intervention strategies.

PMID- 9032826
TI  - Identity, ideology and inequality: methodologies in medical anthropology,
      Guatemala 1950-1995.
AB  - This paper sketches the history of medical anthropology in Guatemala, focusing on
      how investigations carried out during the 1950s served as methodological and
      ideological foundations for subsequent work. Problematic examples from the
      literature and from the author's experience are used to provide insight into the
      nature of the anthropologist's role in applied research and development. For
      example, medical anthropologists are often hired to help navigate the gulf
      between the ideological identities of indigenous peoples and those of biomedical
      researchers and international development specialists. Instead of recognizing the
      inherently ethical nature of this work and acting accordingly, many
      anthropologists have adopted a detached, "scientific" and impossibly value-free
      perspective. This paper proposes a transformation of this role into one that (1)
      maintains an independent and critical relationship to mainstream science, (2)
      elaborates and advocates the indigenous agenda, and (3) adopts an explicitly
      value-filled ideology, methodology and theoretical framework.

PMID- 9032825
TI  - Effects of a randomized health education intervention on aspects of reproductive
      health knowledge and reported behaviour among adolescents in Zimbabwe.
AB  - Unwanted teenage pregnancy and the attendant morbidity and mortality necessitate
      an understanding of the factors influencing adolescent sexuality and the
      implementation of programmes designed to improve their knowledge and reproductive
      behaviour. A randomized controlled study on reproductive health knowledge and
      behaviour was undertaken among adolescent pupils drawn from a multi-stage random
      cluster sample. A self-administered questionnaire was used to assess aspects of
      reproductive health knowledge and behaviour at baseline followed by a health
      education intervention, except for control schools. Results are based on 1689
      responses made up of 1159 intervention and 530 control respondents. There was a
      significant increase in correct knowledge about aspects of menstruation in
      intervention as compared with control schools [odds ratio (OR) = 4.5, 95%
      confidence interval (CI) = 3.4-6.1). Significantly, (OR = 2.0, 95%CI = 1.1-3.9)
      more pupils from intervention than control schools scored correctly on practice
      relating to menstruation. Pupils from intervention schools were more likely (P <
      0.001) to know that a boy experiencing wet dreams could make a girl pregnant and
      that a girl could get pregnant at her first sexual intercourse (OR = 1.4, 95%CI =
      1.1-1.9). Knowledge of family planning was low in both groups at baseline but was
      high at five months follow-up in the intervention schools. The findings point to
      the need for early school-based reproductive health education programmes,
      incorporating correct information on reproductive biology and the subsequent
      prevention of reproductive ill health.

PMID- 9032828
TI  - Conceptualizing oral health and oral health-related quality of life.
AB  - This investigation considers oral health from a health-related quality of life
      perspective using a multidimensional concept representing a combination of
      impairment, function, perceptions, and/or opportunity. A subset of dentate
      individuals aged 18 and older from a national probability sample of the U.S. was
      selected for the reported analysis with data available from personal interviews,
      self-administered questionnaires, and oral examinations. Impairment was
      represented by clinically assessed active diseases and sequelae of diseases and
      self-reported acute symptoms. Other domains are represented by self-reported
      problems with function, perception of control over oral health, satisfaction with
      teeth, value attributed to oral health, and opportunity to obtain dental care.
      Principal components analysis with varimax rotation provided a structure to
      interpret four factors: accumulated oral neglect, self-perceived symptoms and
      problems, reparable oral diseases, and oral health values and priorities.
      Approximately 50% of the variance was explained by these four factors. Factor
      based scores, envisioned as an index or summary measure representing the
      combination of variables identified in each factor, were used to assess potential
      validity. Whites had lower levels of accumulated oral neglect, fewer symptoms,
      and less reparable oral disease, but similar oral health values, than non-whites.
      Level of formal education was associated with each of the four factor-based
      scores. Age was directly associated with accumulated oral neglect, but the
      youngest age group had significantly more reparable oral diseases. Individuals
      with a dental visit in the past two years had considerably less accumulated oral
      neglect, fewer self-perceived problems, less reparable oral disease, and higher
      values of oral health than those without a dental visit in the past two years.
      Ordinary least square regressions were performed on each of the four factor-based
      scores using eight sociodemographic and economic variables. All four regression
      models were significant, with only the education variable being significant
      across all models. These analyses provide no evidence for one unique factor
      representing oral health. Rather, a conceptual framework for oral health appears
      to be represented by a set of reasonably independent components, including two
      groups of clinically assessed oral health, which together more fully represent
      oral health than any one single variable. Conceptualizing and measuring oral
      health multidimensionally leads us closer to examining it as part of general
      health.

PMID- 9032827
TI  - "Ruling in" and "ruling out": two approaches to the micro-rationing of health
      care.
AB  - Much of the implicit rationing said to characterise British health care occurs as
      doctors decide what resources to allocate to individual patients. This paper
      examines this process using data from case studies of selection of patients for
      cardiac surgery and admission to a specialist neurological rehabilitation centre.
      The analysis focuses on cardiac catheterisation conferences in which
      cardiologists present surgical candidates to a cardiac surgeon, and neuro
      rehabilitation admissions conferences in which a multidisciplinary team assess
      the suitability of head injury and stroke patients referred by hospital doctors.
      For much of the time participants in both settings discuss patients within a
      clinical discourse that relies on technical assessments of coronary anatomy, ADL
      scores and the like. However, there are many examples where the discourse "frame"
      shifts to address patient characteristics of a social or moral nature.
      Information of this kind tends to be deployed in two ways: it can be used to
      signal the patient's unsuitability, usually on the basis that past behaviour
      implies poor prognosis ("ruling out"), or it can be used to suggest that a
      patient is especially deserving of help ("ruling in"). Analysis of the data
      suggests that "ruling out" is more salient within the cardiac catheterisation
      conferences, and "ruling in" within the neuro-rehabilitation admissions
      conferences. The authors suggest that this reflects differences in the work
      organisation of the two specialties, including the division of labour, the
      organisation of waiting lists as a queue or a pool, and the putative significance
      of patient agency in the genesis of disease and recovery.

PMID- 9032829
TI  - Refocusing the lens: epidemiologic transition theory, mortality differentials,
      and the AIDS pandemic.
AB  - The epidemiologic transition theory presented first by Omran [Omram. A. R. (1971)
      The epidemiologic transition: a theory of the epidemiology of population change,
      Mildbank Quarterly 49(4), 509-538] was designed to explain global trends in the
      dynamic relationship between epidemiological phenomena and demographic change.
      This paper argues that universalizing this theory only partially serves to
      explain mortality declines over the last century and eclipses key epidemiologic
      differences between population subgroups based on socioeconomic status, race, and
      sex. This paper examines morbidity and mortality differentials between population
      subgroups and demonstrates important inconsistencies with the optimistic trends
      implied by the epidemiologic transition theory, an argument further developed
      using the HIV/AIDS pandemic as a case study. The paper argues that these
      differences should be brought from margins to center to present a more complex
      and comprehensive picture of how population subgroups experience epidemiologic
      transitions differently.

PMID- 9032830
TI  - Prior hospitalization and age as predictors of mental health resource utilization
      in Israel.
AB  - A two-part demand model based on data from a psychiatric case registry was
      estimated in order to search for predictors of hospital-based psychiatric care
      utilization. Using only age as an independent variable, explanation of future
      resource utilization is considerably weaker than when number of cumulative days
      of psychiatric hospital-based service use during the previous five years is also
      included. Only a small marginal gain is achieved by also adding diagnoses.
      Prospective remuneration by capitating sick funds according to age and past
      hospital-based service utilization records is recommended to avoid the twin
      pitfalls of cream-skimming and a distorted allocation of resources for
      psychiatric services.

PMID- 9032831
TI  - "Popular" health and the state: dialectics of the peace process in El Salvador.
AB  - The poor performance of large-scale "vertical" rural health programs tied to
      state Ministries of Health in Third World countries has often been attributed to
      a lack of "political will". But that term tells little about the conditions that
      favor health reform and may obscure disparate power relations and struggles over
      development. This work explores such a struggle over community health that
      emerged as part of the peace process in a former war zone of El Salvador since
      the 1992 ceasefire. The formalized negotiations (and behind-the-scenes
      confrontations) over health in Chalatenango province took place between Ministry
      of Health administrators and proponents of a "popular" health system that has
      functioned in repopulated villages of rebel-controlled Chalatenango since 1987.
      The Ministry has set up its own national (U.S. AID-designed) community health
      worker program, and agreed in theory with the popular system's emphasis on
      village-based lay health promoters; however, in negotiations and efforts at
      collaboration in Chalatenango the Ministry has been unwilling to support the
      promoters in the popular system, to accommodate local participation in health
      decision-making, or to restructure its own physician-centered practices around
      the need for more comprehensive approaches to health.

PMID- 9032832
TI  - The role of decision analysis in informed consent: choosing between intuition and
      systematicity.
AB  - An important goal of informed consent is to present information to patients so
      that they can decide which medical option is best for them, according to their
      values. Research in cognitive psychology has shown that people are rapidly
      overwhelmed by having to consider more than a few options in making choices.
      Decision analysis provides a quantifiable way to assess patients' values, and it
      eliminates the burden of integrating these values with probabilistic information.
      In this paper we evaluate the relative importance of intuition and systematicity
      in informed consent. We point out that there is no gold standard for optimal
      decision making in decisions that hinge on patient values. We also point out that
      in some such situations it is too early to assume that the benefits of
      systematicity outweigh the benefits of intuition. Research is needed to address
      the question of which situations favor the use of intuitive approaches of
      decision making and which call for a more systematic approach.

PMID- 9032833
TI  - Disease ecology and a reformist alternative: the case of infant mortality.
AB  - This paper attempts to shed some light on the recent debate between those who
      advocate a reformed medical geography and those who respond that reform is not
      necessary. We show that disease ecology and a reformist alternative display
      certain tendencies in the ways in which they address issues of health and
      disease. We use the example of geographic variations in infant mortality rates to
      show how two non-positivist perspectives from social theory, political economy
      and humanism, support a reformist viewpoint, while also acknowledging the value
      of a complementary disease ecology approach. Two concepts, the social
      construction of health and illness and social relevance, are used to portray the
      political economy approach; humanism is described in terms of the meaning of
      individual experience and the importance of place. The paper concludes with a
      discussion of the respective roles of disease ecology and a reformist approach in
      models of infant mortality and a summary of the main differences between the two
      perspectives.

PMID- 9032834
TI  - Information sharing in semen donation: the views of donors.
AB  - The authors report on a comparative questionnaire study of semen donors at two
      London clinics offering donor insemination (DI). Results presented here include
      donors' attitudes towards the storage of identifying information on the UK Human
      Fertilisation and Embryology Authority's central register, the importance of
      anonymity when donating, feelings about being traced by DI offspring, and views
      on the release of identifying donor information to mature offspring. Donors from
      the two clinics were found to differ on some, although not all, of the above
      points; in particular, donors from one clinic offered more support for the
      eventual release of identifying information to DI offspring. The discussion
      brings in the results of other studies and highlights the complexity of the
      anonymity question. The authors conclude that some donors may be willing to move
      towards greater openness of information under controlled conditions using the
      existing central register and a "veto" system.

PMID- 9032835
TI  - Shared decision-making in the medical encounter: what does it mean? (or it takes
      at least two to tango).
AB  - Shared decision-making is increasingly advocated as an ideal model of treatment
      decision-making in the medical encounter. To date, the concept has been rather
      poorly and loosely defined. This paper attempts to provide greater conceptual
      clarity about shared treatment decision-making, identify some key characteristics
      of this model, and discuss measurement issues. The particular decision-making
      context that we focus on is potentially life threatening illnesses, where there
      are important decisions to be made at key points in the disease process, and
      several treatment options exist with different possible outcomes and substantial
      uncertainty. We suggest as key characteristics of shared decision-making (1) that
      at least two participants-physician and patient be involved; (2) that both
      parties share information; (3) that both parties take steps to build a consensus
      about the preferred treatment; and (4) that an agreement is reached on the
      treatment to implement. Some challenges to measuring shared decision-making are
      discussed as well as potential benefits of a shared decision-making model for
      both physicians and patients.

PMID- 9032836
TI  - Long-term care experience in Saudi Arabia.
AB  - The objective of this study was to ascertain the clinical and epidemiological
      pattern of long-term care inpatients in Saudi Arabia. A cross-sectional survey of
      all long-term care inpatients facilities in the Ministry of Health was conducted
      during the period January-June 1994. Trained research teams consisting of
      physicians, social workers, nurses and medical record officers completed a pre
      designed data form. They interviewed the treating teams, patients and their
      relatives. The data form consisted of socio-demographic data of patients, the
      duration of their stay in hospital and their clinical, social and psychological
      characteristics. In addition, the perceptions and preferences of doctors,
      patients, and their relatives about patient management in hospital vs home care
      were sought. Out of all patients, 61.3% were males, while 52.7% were elderly
      patients (> or = 60 years of age). Forty-three percent did not need any nursing
      care or required only routine nursing care. The treating doctors believed that
      44.9% of patients could be cared for at home. However, 45.2% of the patients
      preferred to stay in hospital, while 67.5% of their relatives preferred
      institutional care. It is concluded that there is a need to plan for more cost
      effective facilities for these patients. The proposed health services have to be
      culturally acceptable in order to encourage patients and their relatives to
      utilize them.

PMID- 9032837
TI  - Does "process utility" exist? A case study of willingness to pay for laparoscopic
      cholecystectomy.
AB  - This paper is concerned with the concept of process utility in health care. The
      paper begins by outlining the reasons why it might be important to include
      process utility in health care evaluation. Problems in defining process and
      outcome are then outlined, after which the discussion turns to how process
      utility might be detected empirically. Willingness to pay (WTP) is suggested as
      one means of doing so. The methods and results of a survey to test for the
      existence of process utility using WTP applied to laparoscopic cholecystectomy
      are reported. Cholecystectomy patients on a hospital waiting list were asked
      about their WTP for laparoscopic rather than conventional cholecystectomy.
      Willingness to pay was used in two ways to examine whether process is in the
      utility function. First, respondents were randomly allocated to receive different
      descriptions of laparoscopic and conventional cholecystectomy; one group
      receiving a description of differences between the treatments in terms of
      outcomes only, whilst the other group received information on differences in the
      process of treatment as well as on differences in outcomes. The groups were then
      compared in terms of their WTP. Second, regression analysis was used to test for
      the association between WTP and respondents' ratings of reasons for their WTP,
      some of these reasons reflecting process aspects and others reflecting outcome
      aspects. The results lead to rejection of the hypothesis that information on
      process of care would lead to higher WTP. However, due to the design of the study
      and the difficulties in defining process and outcome, it cannot be concluded that
      process utility does not exist. The paper concludes by suggesting alternative
      methods of testing for the existence of process utility.

PMID- 9032838
TI  - Excess female mortality in rural Somalia--is inequality in the household a risk
      factor?
AB  - Gender differences in mortality risks in rural Somali communities were studied to
      assess their relation to literacy, marital status and family economy between
      January 1987 and December 1989. In all, 6947 person-years form the basis for the
      demographic analysis and estimations of mortality rates and survival. Both sexes
      showed similar mortality risks in infancy and early childhood, but females
      demonstrated a greater risk of dying during their reproductive life than males.
      Respiratory symptoms, diarrhoea, fever and jaundice dominated the symptoms prior
      to death Illiteracy in women considerably increased the risk of dying from 15
      years and onwards particularly when living with literate men. The life expectancy
      from 15 years was 58 for a literate male but only 42 years for an illiterate
      woman living with a literate head of household. Multivariate analyses showed
      after adjustment for marital status and literacy that an excess female mortality
      from 15 years, but especially from 45 years, was associated to a household
      situation, where the woman did not subside on farming but on other, mainly
      commercial, activities. This vulnerability of females was associated to the
      recession of the economy in the pre-war situation in Somalia, a backlash hitting
      women trying to earn their living. To conclude, gender differences in a number of
      factors in the household-literacy, marital status and especially source of income
      were disadvantageous for the women, increasing the mortality risk in this
      setting.

PMID- 9032839
TI  - Proceedings of the 7th International meeting of the Leksell Gamma Knife Society.
      Island of Lana'i, Hawaii, November 1995.

PMID- 9032840
TI  - Radiobiological effects of gamma knife radiosurgery on brain tumors studied in
      autopsy and surgical specimens.
AB  - To elucidate the radiobiological effect of Gamma Knife radiosurgery on brain
      tumors, we performed a histological study on nine cases. In two, the material was
      obtained at autopsy and in seven following surgery. In the central region of the
      radiation field, destructive changes occurred both in tumor cells and in vessels.
      In the peripheral area, destructive and proliferative vascular changes were
      intermingled with residual tumor tissue. Immunohistochemical staining of surgical
      specimens showed that the vascular proliferative changes consisted of pericytic
      proliferation with or without endothelial proliferation. These characteristic
      changes might suppress tumor growth, at least in the short-term.

PMID- 9032841
TI  - In vitro contractility studies of the rat middle cerebral artery after
      stereotactic Gamma Knife radiosurgery.
AB  - The middle cerebral artery (MCA) was irradiated in 94 rats using the Gamma Knife.
      The vessels receiving 20, 50, 80 and 200 Gy were removed 24 h later and mounted
      on a myograph. Contractility responses to potassium and prostaglandin (PG) F2
      alpha were tested. After precontraction with PGF2 alpha, the relaxant effects of
      histamine, papaverine, L-arginine and sodium nitroprusside were examined. Other
      vessels were preincubated with ouabain or N omega-nitro-L-arginine methyl ester
      before testing with the relaxant agents. After irradiation, the contractile
      response to maximal potassium and PGF concentrations was diminished, suggesting
      dose-dependent radiation damage to the contractile mechanism. The normal MCA
      shows an initial relaxation in the presence of a low K+ concentration, which is
      Na+, K(+)-ATPase dependent. According to this study, the endothelium-derived
      relaxation function was suppressed by radiation, suggesting that there is an
      early change in irradiated vessels, demonstrable by functional studies, which
      affects both the smooth muscle and endothelial layers.

PMID- 9032842
TI  - First biochemical evidence of differential functional effects following Gamma
      Knife surgery.
AB  - Clinical experience with radiosurgery for epilepsy on lesions located in highly
      functional areas has suggested the possibility of Gamma-Knife-induced functional
      effects without deterioration of the underlying cerebral cortex. To investigate
      these hypothetical functional changes, we have developed a special frame
      dedicated to small-animal radiosurgical experimental models, allowing purely
      atlasguided protocols. The left striatum of the first series of rats was targeted
      with high doses (200 Gy maximum) for validation of this new device. The same
      target was used with lower doses (50 Gy at the 50% isodose) in the second series
      to evaluate the biochemical changes and their chronology. The main biochemical
      changes occurred between 59 and 90 days after Gamma Knife irradiation, with
      different amplitudes depending on the biochemical parameter observed.
      Differential effects were first observed between glutamate decarboxylase and
      choline acetyltransferase, and secondarily between excitatory amino acids (AAs)
      and non-excitatory AAs, particularly gamma-aminobutyric acid. These preliminary
      results need to be confirmed and completed by further experimental studies.
      However, Gamma-Knife-induced differential biochemical effects provide the basis
      for a promising new concept for functional radiosurgery and particularly the
      Gamma Knife surgery of epilepsy.

PMID- 9032843
TI  - Tumor cell proliferation and apoptosis associated with the Gamma Knife effect.
AB  - In this study, the expression of proliferating-cell nuclear antigen (PCNA) and
      Bcl-2 protein was examined in neurinomas, meningiomas, pituitary adenomas, and
      malignant lymphomas before treatment with Gamma Knife radiosurgery. Tumor volume
      was rapidly reduced by radiosurgery in all malignant lymphomas and in some benign
      tumors. The latter had been characterized by strong positive immunohistochemical
      staining for PCNA and Bcl-2. Radiation-induced apoptosis is thought to contribute
      to the low-dose effects of Gamma Knife radiosurgery. A population with a large
      proportion of proliferating cells may be susceptible to the induction of
      apoptosis, and the presence of Bcl-2 may not suppress this Gamma Knife effect.

PMID- 9032845
TI  - Digital subtraction angiography for arteriovenous malformations in stereotactic
      radiosurgery.
AB  - Images coming from digital subtraction angiography (DSA) are affected by a
      perspective distortion due to the use of image intensifiers. As a result, DSA
      cannot be used for the accurate definition of stereotactic coordinates. A
      correction method has been developed to enable the use of DSA for the
      radiosurgery of arteriovnous malformations. A software program and a special
      phantom tool were employed. The phantom is made by a computer-controlled drilling
      machine which makes holes in a Plexiglas plate. It has 865 calibration steel
      spheres with coordinates determined with a precision of 0.01 mm. A calibration
      image is acquired by a personal computer, and the software calculates the
      transformation algorithm to superimpose the image on the known positions of the
      phantom. This algorithm is saved and then recalled to transform the diagnostic
      images.

PMID- 9032844
TI  - Accuracy of stereotactic localisation using magnetic resonance imaging: a
      comparison between two- and three-dimensional studies.
AB  - The accuracy of stereotactic localisation using magnetic resonance (MR) imaging
      has been assessed in a phantom study. Parallel studies compared the accuracy
      obtained. First, a series of two-dimensional (2D) MR slices (transverse, coronal,
      and sagittal) was acquired sequentially to image the three-dimensional (3D)
      volume of the phantom. Then, the same volume was imaged in a 3D MR study in which
      the entire volume was excited simultaneously and 2D slices in transverse,
      coronal, and sagittal planes were then reconstructed from the 3D data set. The
      results showed that the 3D acquisition gave superior results in all three planes,
      and overall it was found that only 1% of the phantom volume was affected by an
      error greater than 2 mm, compared with 11% for the 2D study. New facilities for
      image quality assurance provided in GammaPlan version 3.0 have been tested
      against images from the 2D study with known distortion and consequent
      localisation errors and successfully identified all images in which the
      localisation errors were likely to be greater than 3.7 mm.

PMID- 9032846
TI  - Clinical experience with stereotactic digital subtraction angiography with
      distortion correction software.
AB  - Recently developed software for correction of the geometric distortion in digital
      subtraction angiography was tested clinically. Localization and subsequent
      radiosurgical treatment of intracranial arteriovenous malformations was
      undertaken in 60 patients. During each angiographic series, a series of grid
      images was also acquired. All images were transferred to a workstation where the
      grid images were compared to a previously stored ideal image of the grid. A
      distortion correction was then performed on the grid images. The same pixel-by
      pixel correction was applied to the respective angiographic images. The target
      was outlined on corrected subtracted images on the monitor. The outlined regions
      of interest and reference points were transferred to another workstation for dose
      planning, and the treatment was subsequently executed in the Gamma Knife unit.
      The clinical applicability of the distortion correction program was tested and
      possible sources of error examined. The experience gained is being used for
      further development of the software and for smoother data management and
      reduction of the processing time.

PMID- 9032847
TI  - Do we need conventional angiography? The role of magnetic resonance imaging in
      verifying obliteration of arteriovenous malformations after Gamma Knife surgery.
AB  - Sixteen cerebral arteriovenous malformations (AVMs) were examined to determine
      the role of magnetic resonance (MR) imaging in verifying obliteration. The AVMs
      (mean volume 7.5 cm3, range 2-17 cm3) were treated with Gamma Knife surgery
      between March 1993 and May 1994. Integration of stereotactic MR and stereotactic
      conventional X-ray angiography (XRA) was used for targeting in the Gamma Knife
      surgery. All MR examinations both for targeting and follow-up, were performed on
      a 1.5-Tesla superconductive MR scanner (Signa). Multiple pulse sequences (spin
      echo T1- and T2-weighted MR imaging, and three-dimensional time-of-flight MR
      angiography) were used. The mean maximum target dose was 37.4 Gy (range 25.0-44.0
      Gy). The mean minimum target dose was 20.1 Gy (range 17.5-25.2 Gy). Follow-up
      imaging was performed about every 6 months or when clinically warranted. XRA was
      performed when the AVM was no longer seen on MR images. The time from the last MR
      image to the XRA was within 1 month in nine patients, and longer in seven. MR
      imaging demonstrated regressing AVMs in all patients as early as 3 months after
      Gamma Knife surgery. For seven of the nine patients total obliteration on MR was
      confirmed on XRA within 1 month. In the other two, previous hemorrhage and
      adverse radiation effects probably caused overestimation of AVM obliteration. In
      the remaining seven patients, XRA confirmed the MR observation although the time
      intervals were longer. It is concluded that, for medium- to large-volume AVMs, MR
      can demonstrate not only the regressing AVMs but also verify total obliteration.
      However, verification has to be based on an integration of MR imgaging and MR
      angiography. The use of MR reduces the invasiveness of Gamma Knife surgery for
      cerebral AVMs.

PMID- 9032848
TI  - An evaluation of the accuracy of magnetic-resonance-guided Gamma Knife surgery.
AB  - An evaluation of the systematic accuracy of magnetic resonance (MR)-guided Gamma
      Knife surgery was performed. In two experiments, a cylinder phantom filled with
      dosimeter gel containing ferrous sulfate was fixed to a stereotactic frame. The
      gel phantom was irradiated with the Gamma Knife with a single shot using 4-mm
      collimators. The target point was set at the frame center of the stereotactic
      system giving coordinate values of X = 100, Y = 100, Z = 100. The maximum target
      dose was 15 Gy. MR imaging was undertaken immediately after the irradiation,
      using a superconductive 1.5-T MR scanner. Spin echo T1-weighted images, with
      transaxial, coronal, and sagittal views, were obtained. On the images, points
      with the highest signals were defined as the target point which received the
      maximum dose. Within the dose range of the experiment, this definition is based
      on a linear relationship between the dose to the gel and the T1 relaxation
      shortening after irradiation. The distances between the frame center and the
      target point defined on the MR images in the experiments were 0.12 mm (0.2375
      pixels) and 0.43 mm (0.8515 pixels), respectively. Both are within the mechanical
      accuracy of the Gamma Knife. The imaging study confirms the accuracy of the Gamma
      Knife surgery used in the institution.

PMID- 9032849
TI  - Effect of Gamma Knife radiosurgery on acoustic neurinomas. Assessment by 99mTc
      DTPA-human serum albumin- and 201TlCl-single photon emission computed tomography.
AB  - Single photon emission computed tomography (SPECT) was performed on 16 patients
      with acoustic neurinoma before and 1 and 2 years after Gamma Knife surgery.
      201TICI-SPECT was used to determine tumor viability. Early and delayed images of
      99mTc-DTPA-human serum albumin (99mTc-HSA-D)-SPECT were used to assess tumor
      vascularity and permeability, respectively. There was a statistically significant
      decrease in the 99mTc-HSA-D index of the early image at 1 year (p = 0.013) and at
      2 years (p = 0.018) after Gamma Knife surgery. On the other hand, the 201Tl index
      and the 99mTc-HSA-D index of the delayed image were not significantly different
      from their pretreatment values. These observations demonstrate that a reduction
      in tumor vascularity without a decrease in tumor viability may be one of the
      effects of Gamma Knife surgery on acoustic neurinomas.

PMID- 9032850
TI  - Acoustic neurinomas with macrocysts treated with Gamma Knife radiosurgery.
AB  - Six cases of acoustic neurinomas with macrocystic components are presented. In
      three cases the cystic portion was within the tumor, while in the other three,
      the cyst was peritumoral, in the form of a cul-de-sac within the arachnoid, in
      other words it was not a true tumor cyst. The six tumors are from a series of 74
      acoustic neurinomas treated by radiosurgery with a minimum follow-up of 18
      months. In all cases, enlargement of the associated cyst was observed as early as
      4 months after radiosurgery. Clinical signs and symptoms such as facial weakness,
      trigeminal symptoms, vertigo and dizziness and coordination disorders developed
      between 4 and 8 months. In three cases (two intramural cysts and one combined
      peri- and intramural cyst), subacute microsurgery was performed to treat the
      progression of neurological symptoms. One case had spontaneous rupture of an
      intramural cyst, one case of a peritumoral cyst, after progression showed a slow
      spontaneous size decrease after 2 years, and one case is still under observation.
      In the reported series, the dose at the tumor margin ranged between 11 and 17 Gy
      (mean 13.8 +/- 2.5 [SD] Gy) and the maximal dose between 24 and 40 Gy (mean 30.6
      +/- 6.2 Gy). In view of the findings in this study, one should perhaps be
      cautious in advising radiosurgery for this subgroup of acoustic tumors.

PMID- 9032852
TI  - Gamma Knife treatment of 100 consecutive meningiomas.
AB  - Clinical and imaging results of Gamma Knife treatment of 100 consecutive patients
      with intracranial meningiomas are reported. Only 1 patient refused follow-up
      imaging and her symptoms remain improved after 1 year. Mean values for the
      patient and treatment parameters were age 61 years, duration of symptoms 3.6
      years, time since diagnosis 3 years, average tumor diameter 2.4 cm, surface
      radiation dose 15 Gy and number of isocenters 5. Clinical outcomes revealed that
      6 were improved, 75 were unchanged and 17 had deteriorated. Of the latter, 8 were
      operated, 4 were treated medically and 5 died. Imaging follow-up showed no growth
      in 87 patients. The size of tumors treated ranged from 0.66 to 6.8 cm average
      diameter. In the 77 patients with tumors with an average diameter of 3 cm or
      less, only 2 (3%) showed further growth, and none died of tumor-related causes.

PMID- 9032851
TI  - Gamma Knife radiosurgery in skull base meningiomas. Preliminary experience with
      50 cases.
AB  - Gamma Knife radiosurgery was performed on 50 patients (10 males and 40 females)
      with skull base meningiomas (SBMs) between February 1993 and September 1995. The
      patients ranged in age from 25 to 78 years (mean age 56 years). The location of
      the tumors was anterior fossa (n = 4), sphenoorbital (n = 2), sellar region (n =
      5), cavernous sinus (n = 26), petroclival (n = 12), and occipital foramen (n =
      1). The tumor volume ranged from 0.6 to 20 cm3 (mean 8.6 cm3). The mean values
      for dose planning were edge isodose (EI) 46.7%, edge dose (ED) 18.0 Gy, maximum
      dose 39.8 Gy, average dose (AD) 25.4 Gy, and average number of isocentres 5.7.
      The patients were analyzed for five parameters: tumor volume (< 7.5 vs. > or =
      7.5 cm3); EI (< 50 vs. > or = 50%); ED (< 18 vs. > or = 18 Gy); AD (< 25 vs. > or
      = 25 Gy), and primary versus residual or recurrent tumors. The overall frequency
      of tumor growth control (TGC) was 98%, with 1- and 2-year TGC rates of 97% and
      100%, respectively. The most favorable neurological results were obtained with a
      tumor volume < 7.5 cm3 (p < 0.05), EI > or = 50% (NS), ED > or = 18 Gy (NS) and
      with primary SBMs (p < 0.01). A favorable TGC was demonstrated at follow-up
      imaging examinations when the tumor volume was > or = 7.5 cm3 (100% TGC rate), EI
      < 50% (100%), ED > or = 18 Gy (100%), AD > 25 Gy (100%), in both primary SBMs
      (100%) and residual or recurrent SBMs (96.5%). To date, only 3 (6%) of the 50
      patients have presented signs of neurological worsening related to the Gamma
      Knife radiosurgery. While no early complications were noted, neuroradiological
      follow-up did show delayed transient imaging complications (3 edema and 1
      radionecrosis; 8% of all patients). In conclusion, our preliminary results seem
      to confirm that Gamma Knife radiosurgery is an effective and safe adjuvant or a
      feasible alternative primary treatment in controlling or preventing SBM
      progression.

PMID- 9032853
TI  - Radiation-induced edema after Gamma Knife treatment for meningiomas.
AB  - A retrospective study was performed to analyze some parameters in a consecutive
      series of 35 Gamma Knife treatments in 34 patients with benign meningiomas. The
      minimum dose to the tumors was never less than 12 Gy. The follow-up period was
      from 1 to 3 years. A semiquantitative method of tumor volume assessment was used
      to measure the tumor response to treatment. The presence and clinical
      significance of postradiation edema were noted. Even in this short follow-up
      period, 11 of the 35 tumors were reduced in volume. No tumors increased in size.
      Edema developed preferentially in nonbasal tumors, especially those around the
      midline and sagittal sinus. In all but one case where radiation-induced edema was
      observed was the margin tumor dose 18 Gy or more. It is suggested that doses of
      18 Gy or more should probably be avoided in the Gamma Knife treatment of
      meningiomas and that the greatest care should be taken in selecting non-skull
      base tumors for this form of treatment.

PMID- 9032854
TI  - Gamma Knife radiosurgery for acoustic schwannoma: effects of low radiation dose
      and functional prognosis.
AB  - The effects of relatively low dose Gamma Knife irradiation on acoustic schwannoma
      were evaluated in 29 patients followed over 2 years after treatment. The mean
      dose delivered to the tumor periphery was 12.1 Gy. Lowering of the magnetic
      resonance signal intensity in the tumor center appeared in 69% and signs of tumor
      shrinkage appeared in 59% of cases. The cyst in the tumor enlarged in 3 cases,
      and 2 cases developed hydrocephalus. The percentage of pure-tone hearing
      preservation was 82% at 3 months, 73% at 6 months, 68% at 12 months. 64% at 18
      months and 59% at 24 months in 22 out of 29 cases. Relatively low dose Gamma
      Knife radiosurgery was effective in suppressing tumor growth, with preservation
      of hearing.

PMID- 9032855
TI  - Gamma Knife radiosurgery for meningiomas: four cases of radiation-induced edema.
AB  - We review 48 cases of meningioma treated with Gamma Knife radiosurgery. The mean
      marginal dose was 15 Gy and the mean follow-up was 12 months. Follow-up computed
      tomography and magnetic resonance imaging showed tumor shrinkage in 19 cases,
      central necrosis in 1 case, loss of contrast enhancement in 1 case, and no change
      in 27 cases. We noted 4 cases of radiation-induced edema in supratentorial
      meningiomas.

PMID- 9032856
TI  - Dose distribution and shrinkage of acoustic neurinomas 2 years after Gamma Knife
      treatment.
AB  - To examine the relationship between dose distribution and tumor shrinkage of
      acoustic neurinomas, correlation coefficients between distribution probabilities
      of some dose areas and residual tumor ratios of 21 cases were studied at 2 years.
      Approximating a dose-volume histogram to beta-distribution, two essential dose
      areas for tumor control were extracted: a dose area from 14.2 to 24.7 Gy
      contributed to tumor shrinkage, whereas a dose area from 27.3 to 29.4 Gy was
      contraindicated. Given that there are at least two different dose areas with
      reverse characters, a formula with two opposing logistic components is proposed
      to predict tumor control. With this formula, Gamma Knife treatment of acoustic
      neurinomas may be optimized.

PMID- 9032857
TI  - Radiosurgery for pineal tumors: is biopsy indicated?
AB  - Pineal region tumors can be difficult to biopsy, given the critical structures in
      the location of the pineal gland. Modern computerized imaging techniques like
      computed tomography and magnetic resonance imaging used in association with tumor
      markers and the age at presentation may enable treatment without biopsy using a
      rational treatment algorithm.

PMID- 9032858
TI  - Pineal region tumors: the role of stereotactic radiosurgery.
AB  - Between July 1992 and August 1995, 11 patients with pineal region tumors (PRTs)
      were treated at our center. Ages ranged from 8 to 72 years (median 21). Diagnosis
      was confirmed by histological examination in 7 patients. The remaining cases had
      strong neuroradiological and marker evidence of the diagnosis, so that a
      stereotactic biopsy could be avoided. The pathological diagnoses were
      pinealocytoma (n = 1), tectal astrocytoma (n = 1), germinoma (n = 2),
      pinealoblastoma (n = 2), and meningioma (n = 3). The marginal dose of these
      tumors ranged from 12 to 18-20 Gy. Conventional external radiotherapy was never
      used in this series. With a median follow-up of 12.3 months (range 2-34), all
      tumors responded to treatment and disappeared or ceased growing. We observed no
      mortality or major morbidity. One patient (tectal astrocytoma) had a mild
      radiation-induced reaction, with headache and transient worsening of an abducent
      nerve palsy, which were controlled with steroids. In germinomas and
      pinealoblastomas, recovery of normal cerebrospinal fluid circulation was observed
      in less than 7 days, in parallel with major tumor shrinkage. In this study we
      confirm that radiosurgery can be an effective and safe alternative for the
      treatment of pinealocytomas and low-grade tectal gliomas. Moreover, we consider
      that the characteristics of the radiosurgery technique suggest the method should
      be evaluated for the treatment of malignant PRTs.

PMID- 9032859
TI  - Two cases of Gamma Knife radiosurgery for low-grade optic chiasm glioma.
AB  - The effect of radiosurgery on optic gliomas is uncertain. We report two cases of
      low-grade glioma of the optic nerve and chiasm treated by transcranial subtotal
      removal and Gamma Knife radiosurgery. The first case was a 2-year-old boy,
      admitted with visual disturbance and nystagmus. Histopathological examination
      showed a pilocytic astrocytoma. The tumor volume was 14.4 cm3. Dose planning was
      performed using axial and coronal T1-weighted enhanced images. The marginal dose
      was 12 Gy at the 40% isodose line. The dose to the optic apparatus was less than
      9 Gy. The second case was a 47-year-old woman, admitted to our hospital with
      headache and visual disturbance. The histopathological findings showed a
      fibrillary astrocytoma. The tumor volume was 12.3 cm3. The marginal dose was 14.4
      Gy at the 40% isodose curve. The follow-up periods for the two cases were 24 and
      43 months, respectively. In both cases the most recent follow-up magnetic
      resonance scan showed a marked decrease in tumor size, and visual symptoms were
      improved. No postradiosurgical complications have developed to date. Gamma Knife
      radiosurgery could be an effective adjuvant therapy for low-grade optic glioma.
      However, long-term follow-up is required for further evaluation of the efficacy
      and potential side effects.

PMID- 9032860
TI  - Gamma Knife radiosurgery for intracranial metastases: from local tumor control to
      increased survival.
AB  - We have analyzed a series of 225 patients with intracranial metastases (343
      lesions), treated in our department by Gamma Knife radiosurgery over a 30-month
      period. We have used a modified Pittsburgh protocol and performed 242 procedures
      on 164 single/78 multiple lesions. Primary tumors were mostly carcinomas of the
      lung (52%) and breast (11.6%). Neuroradiological localization of the target was
      usually performed by stereotactic computed tomography. Magnetic resonance imaging
      was only used in special circumstances. Routine dose planning was assisted by
      three-dimensional reconstruction programs. Mean tumor volume was larger than
      expected (5.7 ml). Mean prescription dose and average dose were 21.1 and 29.9 Gy,
      respectively. Middle- and long-term results were evaluated in a subset of 152
      patients (236 lesions) with adequate (> 4 months) follow-up. Mean follow-up was
      53.1 weeks with 61/152 patients still living. There was a predominance of
      retrospectively classified 'not fully eligible cases' among the survivors, mainly
      because of uncontrolled primary tumor. The 1-year local tumor control rate was
      88.2%. Treatment-related radiological (3.9%) and clinical (1.6%) sequelae were
      minimal. Overall mean survival in these patients (40 weeks) turned out to be
      higher than that commonly reported after conventional surgical-radiation
      treatments. It was encouraging that the mean survival of 'fully' eligible
      patients was 51 weeks. Karnofsky performance status and neurological (Order
      Grading) performance scores were consistently high for most of the follow-up
      period. Functional Independence and the Palliative Index were not far from the
      value of mean survival. The main cause of death remains uncontrolled systemic
      disease (64.8%). On the other hand, the relative incidence of intracranial tumor
      progression was considerably decreased. This indicated that these patients should
      perhaps be treated more aggressively and underlines the need for randomized
      trials to determine the optimal treatment.

PMID- 9032861
TI  - Radiosurgery of brain metastases with the Gamma Knife.
AB  - A total of 130 patients with metastatic brain tumors were treated with the Gamma
      Knife; 85 had multiple lesions. The marginal dose was 14-30 Gy for the initial 20
      cases during the first 6 months. Thereafter, we increased the marginal dose to
      between 25 and 30 Gy for the last 110 cases. The follow-up period ranged from 1
      to 49 months (mean 9 months). The recurrence rate fell from 20% for the early low
      dose cases to 4.6% for the later 110 higher-dose cases (p = 0.043). Transient
      neurological deterioration developed in 7 cases (5.4%), and permanent
      neurological deficits were recognized in a further 6 cases (4.6%). The relatively
      high prescription dose of 25-30 Gy at the margin of brain metastases treated with
      the Gamma Knife resulted in an acceptably high control rate with a low rate of
      complications.

PMID- 9032862
TI  - Preliminary application of Gamma Knife in the treatment of nasopharyngeal
      carcinoma.
AB  - Nasopharyngeal carcinoma is a malignant tumor which occurs frequently in China.
      Currently, radiotherapy using 60Co is the main method of treatment. However, the
      5-year survival rate is only 49.5%. There is no effective method today for
      treating residual or recurrent tumor following radiotherapy. In principle, the
      Leksell Gamma Knife could contribute to better results. Since December 1993, we
      have treated 36 patients suffering from nasopharyngeal carcinoma with the Gamma
      Knife: 32 were relapses after radiotherapy and 4 were primary cases. Treatment
      was very effective for a short period. The rate of improvement of such symptoms
      as headache, facial paralysis, reduced vision, nasal obstruction and nasal
      bleeding was 70-100%. After treatment, tumors became smaller or even disappeared.
      A new nasopharyngeal biopsy was performed in 12 patients and demonstrated that
      the pathological tissue had returned to normal. The short duration of the survey
      precludes conclusions about the long-term effects of the treatment.

PMID- 9032863
TI  - Gamma Knife stereotactic radiosurgery for uveal melanoma: clinical results after
      2 years.
AB  - We report on 36 cases of uveal melanoma treated at our center between March 1993
      and September 1995. There were 16 men and 20 women, aged 57 +/- 11 years. The
      choroid was affected in 35 patients and the ciliary-body in 1. The same
      preoperative and follow-up protocol was adopted for all cases. The procedure
      included fixation and positioning of the eye with a retrobulbar injection of long
      lasting anesthetic and two extraocular muscle sutures, application of the frame,
      computed tomography scan localization, dose planning and treatment with the Gamma
      Knife. The patients were divided into three groups. Group A: 10 patients with a
      follow-up of 24 +/- 4 months, treated with a high dose (surface dose 58 +/- 9 Gy,
      maximum dose 81 +/- 15 Gy, mean dose 66 +/- 11 Gy). Group B: 9 patients with a
      follow-up of 16 +/- 2 months, treated with a lower dose (surface dose 41 +/- 3
      Gy, maximum dose 76 +/- 10 Gy, mean dose 53 +/- 11 Gy). Group C: 17 patients with
      a follow-up of 6 +/- 3 months, treated with a lower dose (surface dose 42 +/- 3
      Gy, maximum dose 72 +/- 16 Gy, mean dose: 54 +/- 6 Gy). In group A, we observed
      marked tumor regression in 9 cases, tumor recurrence in 1 case and severe
      complications in 5 cases (neovascular glaucoma and/or radiation retinopathy
      and/or radiation optic neuropathy). In group B, significant local control of the
      tumor was obtained with minor complications (cotton wool spots hard exudates,
      intraretinal hemorrhages). In group C, to date we have observed a regression of
      the tumor in 7 cases and 1 severe complication (neovascular glaucoma). Our data
      show that uveal melanomas may be adequately controlled by a high radiosurgical
      dosage (50-70 Gy), though there are significant side effects. Comparable levels
      of local tumor control may be obtainable using lower doses (40-45 Gy) which would
      hopefully reduce the rate of complications. However, a longer follow-up is needed
      for further validation of these results.

PMID- 9032864
TI  - Positron emission tomography using 18F-fluorodeoxyglucose in patients with
      stereotactically irradiated brain metastases.
AB  - Thirty-one patients with intracranial metastases were examined with positron
      emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) as a tracer. The PET
      study was prompted by growth of the tumor in spite of therapy, or regrowth after
      an initially favorable response. Increased accumulation of FDG was seen in 14
      patients (group 1) and decreased in 17 (group 2). Patients in group 1 had
      verified tumor growth in 9 of 14 cases. The median survival after radiosurgery
      was 12.3 months. One patient in this group is still alive after open surgery of a
      recurrent metastasis. Six patients in group 2 are still alive. The median
      survival after radiosurgery was 19.9 months. Verified radiation reaction/necrosis
      was found in 5/17 and viable tumor tissue in 2. The survival time in group 2 was
      significantly longer than in group 1. PET is superior to computed tomography and
      magnetic resonance imaging in the differentiation between recurrence and
      radiation reaction/necrosis. However, temporary radiation effects may mask
      remaining tumor tissue, and repeat PET studies may sometimes be necessary.

PMID- 9032865
TI  - Gamma Knife radiosurgery for brain stem metastases: two autopsy cases.
AB  - Early neuropathological findings were obtained at autopsy in two cases of brain
      stem metastasis treated with the Gamma Knife. In both cases, light microscopy
      radiation changes were strictly localized. Residual tumor tissue in the
      irradiation field showed marked degenerative changes including multinuclear
      cells, atypical nuclei and vacuolar degeneration. A characteristic finding in the
      irradiation field was fibrosis associated with hyalinized and thickened vessels.
      In more peripheral regions, demyelination and vacuolar degeneration were seen.
      This is the first report demonstrating extravascular fibrosis in the irradiated
      field following radiosurgery.

PMID- 9032866
TI  - Is unchanged tumor volume after radiosurgery a measure of outcome?
AB  - We report three patients who underwent Gamma Knife radiosurgery for benign tumors
      (meningioma, neurinoma and hemangioblastoma), in whom an 'unchanged tumor volume'
      demonstrated by postirradiation follow-up neuroimaging could be regarded as a
      successful treatment results, as compared with preradiosurgery tumor growth. It
      is our view that unless significant tumor growth has been observed before
      radiosurgery, 'unchanged in size' after radiosurgery cannot be regarded as a
      successful treatment result. Because relatively few hemangioblastoma patients
      have been treated radiosurgically, this report emphasizes the course of one case
      with hemangioblastoma.

PMID- 9032867
TI  - Irradiation effects on the metabolism of metastatic brain tumors: analysis by
      positron emission tomography and 1H-magnetic resonance spectroscopy.
AB  - To evaluate irradiation effects on the metabolism of metastatic brain tumors
      treated by Gamma Knife radiosurgery, positron emission tomography (PET) and 1H
      magnetic resonance spectroscopy (MRS) studies were performed on five patients.
      The tumor origins were lung cancer in three patients and breast cancer in two.
      Treatment volume was 0.4-10.1 cm3 (mean: 5.5 cm3). The marginal dose to the tumor
      was 24-30 Gy (mean: 26.2 Gy). The follow-up period was 5-19 months (mean: 13.4
      months). No patients had conventional whole-brain radiation therapy. 18F
      fluoroboronophenylalanine (18FBPA) or 18F-fluorodeoxyglucose (18FDG) were used as
      tracers for the PET study. Using 1H-MRS, several metabolites were simultaneously
      measured in metastatic brain tumor and adjacent brain. In the PET study of the
      representative case, the uptake rate of 18FBPA that is actively transported to
      the tumor decreased markedly 15 days after radiosurgery and continued to decrease
      thereafter. In the 1H-MRS study, choline, which is characteristically high in
      metastatic brain tumors, also decreased over time. In two cases with suspected
      radiation injury, the enhanced region, which was decreased in size in early
      follow-up, enlarged progressively and was accompanied by edema. However, 18FBPA
      and 18FDG were not transported to the enhanced region. The peak of free lipid,
      which might show destruction of the cell membrane, was recognized in the enhanced
      region and adjacent brain in these cases. This study revealed that radiation
      effects on the metabolism of metastatic brain tumors occur at an early stage
      after radiosurgery and continue over several months. In particular, in the case
      of radiation injury, PET and 1H-MRS studies made it possible to distinguish
      between regrowth of the tumor and radiation injury.

PMID- 9032868
TI  - Prediction of results following Gamma Knife surgery for brain stem and other
      centrally located arteriovenous malformations: relation to natural course.
AB  - Two models for predicting the results of Gamma Knife surgery for brain stem and
      other centrally located arteriovenous malformations (AVMs) are presented. By
      using these models, the probability of total obliteration and the risk of
      complications can be predicted. The model to predict the probability for
      obliteration is based on the following two observations. First, there is a
      positive relationship between the minimum dose given to the AVM nidus and the
      incidence of obliteration. Second, there is a negative relationship between the
      AVM nidus volume and the minimum dose given in the obliterated cases. The risk
      estimation model is also based on two observations. First, centrally located AVMs
      carry a higher risk of complications than those located peripherally. Second, the
      average dose to volumes which are large for radiosurgery is related to the
      incidence of complications. The findings of this study may be used to estimate
      the consequences of Gamma Knife treatment for every individual case prior to the
      treatment. This makes a comparison between different treatment options and no
      treatment possible. The risk of hemorrhage without any treatment is also
      quantified.

PMID- 9032869
TI  - Dynamic and static scintigraphic evaluation of cerebral arteriovenous
      malformations to evaluate radiosurgical treatment.
AB  - The radiobiologic changes induced by cobalt-60 gamma irradiation in cerebral
      arteriovenous malformations (AVMs) is a torpid process. Complete obliteration may
      take 1 or 2 years or even longer. Neuroradiological modalities like magnetic
      resonance imaging (MRI) and magnetic resonance angiography (MRA) do not provide
      sufficient information to comprehend this process. Digital subtraction
      angiography represents an invasive method and is therefore most often performed
      when complete obliteration is expected. The purpose of this study was to
      investigate the value of blood pool scintigraphy and functional imaging, such as
      single photon emission computed tomography (SPECT), to gain more knowledge about
      the volumetric changes of AVMs treated by radiosurgery. Twenty consecutive
      candidates for Gamma Knife treatment were selected for comparative MRI/ MRA and
      scintigraphic studies. All lesions ranging from 0.6 to 18.6 cm3 could be
      identified on blood pool and SPECT images. Seven patients had repetitive
      examinations at 3-month intervals to compare the relative volumetric change of
      the lesion. In 5 cases, a marked decrease in blood pooling was noticed after 3
      months, and in 2 patients no significant change was evident. In contrast, MRI/MRA
      scans done at the same time did not similarly indicate progressive obliteration
      changes. This preliminary result indicates that scintigraphic evaluation using
      the blood pool technique is a very sensitive method to describe the relative
      volumetric change of radiosurgically treated AVMs.

PMID- 9032870
TI  - Pathobiology of cerebral gliomas in children and the role of radiosurgery.
AB  - Twenty-five gliomas of the cerebral hemisphere in children were examined. Most
      hemispheric gliomas in children have relatively clear margins and less
      infiltrative potential. Radiosurgery has a role in the treatment of these tumors
      in addition to reducing the risk of radiation injuries developing later. Fifteen
      patients were alive 1-27 years (mean 8.4) following treatment and 10 patients
      died. Histologic examination demonstrated 10 differentiated gliomas, 10 poorly
      differentiated gliomas and 5 other gliomas. Most tumors had relatively clear
      margins on computed tomography and/or magnetic resonance images, and peritumoral
      edema was slight. In 9 autopsy cases, tumor dissemination and/or metastasis were
      seen in 7. However, tumor infiltration was not extensive, and clear tumor margins
      were found in some cases. Thus, cerebral gliomas in children have relatively
      clear margins and low infiltrative potential. Radiosurgery has a role in the
      treatment of these tumors.

PMID- 9032871
TI  - Comparison between adult and pediatric arteriovenous malformations treated by
      Gamma Knife radiosurgery.
AB  - More than 290 cases of cerebral arteriovenous malformation have been treated at
      our hospital by Gamma Knife radiosurgery since May 1991, of which 99 were
      followed with angiography for 1 year or more. The results from adult and
      pediatric age groups were compared. There were 70 adults and 23 children.
      Previous hemorrhage had occurred in 73.7% of the adults and 91.3% of the
      children. The mean volume of the nidus was similar in both groups: 4.2 cm3 in
      adults and 4.8 cm3 in children. In both groups approximately 70% of the cases
      fell into Spetzler and Martin grade III. The mean margin dose was 20.0 Gy in the
      adults and 20.5 Gy in the children. Complete nidus occlusion at 1 year occurred
      in 45% of the adults and 74% of the children. The rates at 2 years were 81 and
      94%, respectively. Complications occurred only in adults and consisted of 2
      rebleeds, 1 radiation edema and 1 radiation necrosis. Gamma Knife radiosurgery is
      considered to be safer and have a higher success rate in children than in adults.

PMID- 9032872
TI  - The open Gamma Knife Center concept.
AB  - A freestanding Gamma Knife radiosurgery center has been open for just over 1 year
      in La Jolla, Calif., USA, located in the grounds of a medium-sized community
      hospital. The center employs a full-time medical physicist and neurosurgical
      nurse together with clerical personnel. The neurosurgeons and radiation
      oncologists are drawn from the entire community and bill their fees separately.
      Written protocols for each indication to be treated govern patient eligibility
      and suggested treatment algorithms. Additionally, each patient to be treated is
      presented in conference, and a treatment strategy (i.e., radiosurgery,
      craniotomy, conventional radiation therapy) is decided. Twenty new physicians and
      physicists have begun training to use the Gamma Knife in the first year.
      Certification must be achieved before a clinician can be physician of record.

PMID- 9032873
TI  - Stereotactic dose computation and plan optimization using the convolution
      theorem. I. Dose computation.
AB  - With Leksell Gamma Knife stereotactic radiosurgery, the dose distribution
      delivered by a specific helmet can be assumed to remain as a fixed-dose
      distribution when the shot is moved to different locations within the predefined
      dose calculation matrix. The convolution theorem may be implemented to take
      advantage of this fact for fast dose computation and plan construction. Using
      this technique, the shot spatial arrangement is formulated as a convolution
      kernel, which is theoretically a three-dimensional multi-delta function. The dose
      distribution is computed by the convolution of this single-shot dose distribution
      with the shot convolution kernel. To determine the shot arrangement, an ideal
      dose distribution is generated based upon the target structure. Deconvolution is
      then applied to find the convolution kernel which best fits the proposed ideal
      dose distribution. The primary task of this presentation is to focus on and
      describe in detail the dose computation using the convolution theorem.

PMID- 9032874
TI  - Electrophysiological target localization is not required for the treatment of
      functional disorders.
AB  - A total of 117 patients underwent 124 functional stereotactic procedures with the
      Leksell Gamma Knife to treat trigeminal neuralgia, movement disorders and chronic
      pain. Target identification was performed with stereotactic magnetic resonance
      imaging alone without electrophysiologic localization. Clinical observation of
      these patients over 1-41 months indicates that the efficacy of the procedure is
      comparable with that seen with open stereotactic procedures where
      electrophysiological localization is used. Using current techniques, the
      complications of functional neurosurgery with the Gamma Knife are nearly
      nonexistent. We believe that functional neurosurgery can be performed effectively
      and safely without electrophysiological localization, using the Leksell Gamma
      Knife.

PMID- 9032875
TI  - Lesion size following Gamma Knife treatment for functional disorders.
AB  - In this study we investigated the reproducibility and consistency of the size of
      radiosurgical lesions produced for functional disorders. The T1 gadolinium
      enhanced magnetic resonance (MR) images of 56 patients treated for parkinsonism,
      pain, or other functional diseases were used to measure 140 lesion sizes at
      various times after radiosurgical treatment (1-26 months, mean: 11.3 months).
      Only the 4-mm collimator was used to create the lesions. The maximum dose ranged
      from 110 to 180 Gy (mean: 145 Gy). In 42 cases (78%), one isocenter was used to
      create the lesion. Thirteen lesions (20%) were created with two isocenters and in
      1 case, three isocenters were used. Lesions were detectable on MR images as early
      as 30 days after treatment. The maximum lesion volume was reached after 6-12
      months and ranged from nondetectable to more than 4,000 mm3. Larger lesion
      volumes were strongly associated with the use of more than one isocenter. In
      addition, maximum doses of 160 Gy or more increased the likelihood of producing
      lesions larger than expected. It is therefore concluded that the use of the Gamma
      Knife for the treatment of functional disorders is safest when single-isocenter
      shots with the 4-mm collimator and a maximum dose of less than 160 Gy are used.

PMID- 9032876
TI  - Stereotactic Gamma thalamotomy for the treatment of parkinsonism.
AB  - From September 1994 to June 1995, eight patients with intractable parkinsonism
      underwent gamma thalamotomy in our hospital. All of these patients were male,
      with an average age of 59.3 years. The duration of the disease from initial
      diagnosis was 2-10 years (mean 6.8 years). All had failed or had serious side
      effects with antiparkinsonian medicine. Seven cases had tremor-dominant symptoms,
      while the other had mainly rigidity. Six cases had bilateral symptoms. Computed
      tomography or magnetic resonance imaging (MRI) was undertaken prior to treatment
      in all cases to exclude focal brain lesions. Stereotactic MRI was taken with the
      Leksell frame in place and both T1- and T2-weighted images were obtained. The
      targets were located in the area of Vim/Voa/Vop based on the Schaltenbrand atlas.
      In seven cases, two plugged 4-mm-collimator shots were used. The maximum dose was
      160 Gy in six cases and 180 Gy in one case. In another case, a single 4-mm
      collimator shot was used, and a maximum dose of 160 Gy was delivered to the
      target center. The border of the internal capsule was outside the 20-30% isodose
      line. We intended the 50% isodose line to have an oval-shaped region with the use
      of two shots and should correspond to the shape of Vim. Follow-up data were
      available for six patients (mean: 4.5 months, range: 2-9 months). Tremor
      disappeared in three cases and improved in the other three. In one of these six
      cases, the tremor disappeared just 3 days after gamma thalamotomy. Rigidity
      improved in four of these six cases. In only one patient, treated with a maximum
      dose of 180 Gy, was there any contralateral limb weakness, which developed 3
      months after treatment and has been recovering gradually. Follow-up MRI T2
      weighted images in this case showed that the diameter of the lesion was larger
      than intended and there was a region of diffuse edema in the thalamus and upper
      brain stem. No other complications occurred in this series.

PMID- 9032877
TI  - Gamma thalamotomy for parkinsonian and other kinds of tremor.
AB  - On the basis of our experiences with selective ventralis intermedius thalamotomy
      with microrecording, certain cases of tremor with Parkinson's disease (PD, six
      cases), intentional tremor (one case) and essential tremor (one case) were
      treated by Gamma Knife. In all cases, 140-150 Gy were irradiated using 4-mm
      collimators. Three different strategies were used. (1) Gamma thalamotomy as the
      primary surgical treatment. (2) As a secondary treatment, irradiation of the
      symmetric point of the contralateral selective thalamotomy. (3) Extension of the
      previous thalamotomy. For the first three cases (all PD), a special plug pattern
      (100 plugs) was used, but was not employed for the later cases. No acute untoward
      effects were noted, and overall there appeared to be a reduction in tremor. The
      time course of tremor reduction varied from case to case, from about 5-6 months
      to 1 year.

PMID- 9032878
TI  - Trigeminal neuralgia radiosurgery: the University of Pittsburgh experience.
AB  - The results of Gamma Knife stereotactic radiosurgery in the management of 51
      patients who had typical trigeminal neuralgia were evaluated at the University of
      Pittsburgh. In all cases, a 4-mm isocenter was targeted at the proximal nerve at
      the root entry zone. The target dose varied from 60 to 90 Gy. Forty-four patients
      (86%) had undergone prior surgery. The mean follow-up after radiosurgery was 9.6
      months (range, 2-29 months). The initial response rate was 86%. At the last
      follow-up, 19 patients (37%) had excellent control (pain free), 21 (41%) had good
      control (50-90% relief), and 11 (21%) had failed treatment. No patient developed
      further sensory loss or deafferentation pain. A maximum radiosurgery dose > or =
      70 Gy was associated with a significantly greater chance for complete pain
      relief. Using magnetic resonance imaging stereotactic targeting, the proximal
      trigeminal nerve is an appropriate anatomic target for radiosurgery. Gamma Knife
      radiosurgery is a useful additional surgical approach in the management of
      medically or surgically refractory trigeminal neuralgia.

PMID- 9032879
TI  - Long-term follow-up of stereotactic Gamma Knife radiosurgery in epilepsy.
AB  - From June 1990 to May 1995, 31 patients with epilepsy were treated by
      stereotactic Gamma Knife radiosurgery at the Asan Medical center. The effect of
      radiosurgery for epilepsy was assessed in 23 patients followed for longer than 1
      year. The seizures were medically intractable in all patients: generalized in 13
      cases, complex partial in 6 cases and partial in 4 cases. The duration of
      epilepsy ranged from 1 to 25 years, with a mean of 11.6 years.
      Electroencephalography and magnetic resonance imaging (MRI) were performed in all
      patients to identify and localize the seizure focus. The lesions on MRI were
      nonprogressive and less than 2.0 cm in diameter. At follow-up, 12 patients had an
      excellent result (class I according to Engel's classification). In 3 of these
      patients, antiepileptic medication was discontinued. In a further 2 patients, the
      seizure frequency decreased (class II and III). In the remaining 9 patients, the
      frequency of seizures was unchanged (class IV). Radiation-induced edema did not
      seem to affect the outcome with respect to seizure control. The role of
      radiosurgery in the treatment of epilepsy is still unclear. It is premature to
      draw any definite conclusions about its efficacy for intractable epilepsy in our
      series. However, even this small group certainly suggests the possibility of a
      new safe treatment method in selected patients.

PMID- 9032880
TI  - A comparison of craniotomy and Gamma Knife charges in a community-based Gamma
      Knife Center.
AB  - The hospital charges for all craniotomies and transsphenoidal procedures were
      gathered for a 4-year period from a single, non-profit hospital serving San
      Diego. Calif., USA. Of the individuals in this community 65% are covered by a
      variety of managed health care programs which have greatly discounted hospital
      receipts on a per diem or capitated payment basis. A total of 104 operative cases
      were identified. Forty-six patients (44%) were judged to have been eligible for
      Gamma Knife surgery. The average hospital charge for intracranial surgery on
      Gamma-Knife-eligible individuals was 14% greater than the nominal Gamma Knife
      surgery charge would have been. The complication rate for treated Gamma-Knife
      eligible individuals was 15% including blindness in one eye after removal of a
      tuberculum sella meningioma, and hemiplegia following a delayed postoperative
      hemorrhage after arteriovenous malformation resection in another patient. Actual
      hospital net receipts were 55% of charges and probably approached the true
      hospital cost per procedure. When these hospital receipts were compared to the
      estimated cost per procedure of Gamma-Knife surgery, Gamma Knife surgery had a
      30% cost advantage over surgical resection.

PMID- 9032881
TI  - Evolution and organization of a regional Gamma Knife Center.
AB  - The Gamma Knife is considered by many to be the 'gold standard' radiosurgery unit
      throughout the world. However, its benefits must be weighed against its cost and
      availability. A comparison was made between two tertiary-care, not-for-profit,
      medical-school-affiliated medical centers located in northeastern Ohio. Both
      applied for a certificate of need for a Leksell Gamma Knife. A requirement for on
      site imaging and anesthesia support at one site resulted in considerable extra
      costs. One center then altered its application for a Gamma Knife to be used by
      its own four neurosurgeons. The other center modified its proposal to create a
      Gamma Knife center at the perimeter of its medical center, yet attached to
      existing imaging facilities. It would also allow regional hospitals, patients,
      health plans and qualified physicians and researchers to have access to the unit.
      This plan resulted in a marked reduction in costs. Moreover, it was estimated
      that this plan would greatly increase the volume of treated patients. This was
      the proposal endorsed by the regional Health Systems Agency by a vote of 19 to 1.
      The proposal from the other center for a closed system was rejected.

PMID- 9032882
TI  - Jenner Jabs James Phipps with live cowpox.

PMID- 9032883
TI  - Hib-EuroSud'95: the South exists.

PMID- 9032884
TI  - Vaccine coverage of Streptococcus pneumoniae in Hong Kong with attention to the
      multiple-antibiotic-resistant strains.
AB  - Two hundred and four isolates of Streptococcus pneumoniae obtained from children
      and adults in Hong Kong between January 1993 and May 1995 were analysed for
      serotype and serogroup (SGT) distribution and antibiotic resistance. The
      predominant serogroups and serotypes (SGTs) were 23, 19, 6 and 3 which accounted
      for 19.6%, 16.7%, 15.2% and 7.8% of all isolates, respectively. Altogether, 83.8%
      of all isolates were related to the current 23-valent pneumococcal vaccine. Sixty
      six (32.4%) isolates demonstrated multiple antibiotic resistance, defined as
      resistance to three or more different antibiotics. SGTs 19, 23 and 6 occurred
      significantly more frequently in this group than in the groups with less
      antibiotic resistance (97% vs 30%; P < 0.001). Isolates shown to be resistant to
      all five antibiotics tested (penicillin, chloramphenicol, ceftriaxone, macrolides
      and tetracycline) were found only in serogroups 6, 19 and 23. The 23-valent
      vaccine should cover 84.4% (152/180) of SGTs with one or more antibiotic
      resistance in all age groups, while the proposed 9-valent global pneumococcal
      conjugate vaccine should cover 85.0% (34/40) of such SGTs in children.

PMID- 9032885
TI  - Immune responses in mice induced by HSV-1 glycoproteins presented with ISCOMs or
      NISV delivery systems.
AB  - The purpose of this study was to evaluate the immunogenicity of a herpes simplex
      virus type I (HSV-1) antigen preparation, obtained following zwitterionic
      detergent treatment of virus, and incorporation of the antigens into either
      immunostimulating complexes (ISCOMs) or non-ionic surfactant vesicles (NISV)
      delivery systems. Using Balb/c mice the ISCOM and NISV HSV-1 vaccines were
      assayed for their capacity to induce and enhance both the humoral and cellular
      immune responses, and to elicit protection against both homologous and
      heterologous virus challenge. The serum from animals vaccinated with either the
      NISV or the ISCOM HSV-1 antigen preparation, were found to contain high levels of
      total IgG and IgG1 and IgG2a subclass antibodies. In addition, both preparations
      were found to induce high neutralizing (NT) antibody levels following a two
      immunization protocol and to provide some protection against homologous and
      heterologous HSV challenge infection. Lymphoproliferative responses were observed
      in cultures of splenocytes from mice immunized with both HSV-1 NISV vaccine and
      HSV-1 ISCOMs vaccine, following various antigenic stimuli in vitro. In general,
      these were most marked in animals immunized with the HSV-1 NISV preparation, and
      particularly so when the splenocytes were stimulated in vitro with live HSV-1.
      Both the NISV and ISCOM HSV-1 vaccines were found to have induced interleukin 2,
      interleukin 10 and interferon-gamma in spleen cell culture supernatants, although
      again, the highest responses in general were observed in supernatant fluids from
      spleen cell cultures from animals immunized with the HSV-1 NISV preparation.
      These results suggest that a wide range of immune activity can be elicited by HSV
      1 antigens presented to the immune system of mice in these formulations.

PMID- 9032886
TI  - Antigenicity of hepatitis C virus envelope proteins expressed in Chinese hamster
      ovary cells.
AB  - A putative second envelope glycoprotein (E2) of hepatitis C virus (HCV) was
      constitutively produced in a Chinese hamster ovary cell line stably transformed
      with a plasmid expressing E2 protein under the control of an exogenous promoter
      and a signal sequence. E2 protein that lacked part of the C-terminal hydrophobic
      region was glycosylated with high-mannose type oligosaccharides and retained in
      the cells. On the other hand, E2 protein lacking the entire C-terminal
      hydrophobic region was glycosylated with complex type oligosaccharides (complex
      form) and excreted into the culture medium. Immunoreactivity of the high-mannose
      and complex forms of E2 proteins against sera from HCV infected patients were
      analyzed. We found that the antigenicity of the complex form of E2 protein was
      greater than that of the high-mannose form of E2 protein. This result indicated
      that the complex form of the E2 protein is superior for use in diagnosing HCV
      infection.

PMID- 9032887
TI  - The hemagglutination inhibition antibody responses to an inactivated influenza
      vaccine among healthy adults: with special reference to the prevaccination
      antibody and its interaction with age.
AB  - The immunogenicity of the trivalent split-virus influenza vaccine was
      investigated among 70 healthy adults (mean age: 48.5, range: 36-68). The vaccine
      antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and
      B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or
      more rise on the average in the hemagglutination inhibition (HAI) antibody to
      each antigen. The response rates (greater than or equal to a fourfold rise) were
      about 90% or more among those with a prevaccination titer < or = 1:64 (equivalent
      to < or = 1:16 on the Western scale; in Japan, the HAI titers are expressed by
      the final, and not the initial, dilution of the serum; from hereon our findings
      will be expressed using the Japanese scale), whereas they were 0-50% at > or =
      1:128. Thus, the prevaccination titer was negatively associated with antibody
      induction. The achievement rates (postvaccination titer > or = 1:128) among those
      with a prevaccination titer < 1:16 remained at 48-68%. Regarding the analysis of
      variance, a significant effect on antibody induction was indicated for the
      prevaccination titer (P < or = 0.002), but not for age (P > or = 0.425). The
      interaction between the prevaccination titer and age was significant for
      A/Yamagata (P = 0.030), while it was also suggestive for A/Beijing (P = 0.054):
      as age increased, those with no preexisting antibody (< 1:16) showed greater
      titer rises, in contrast to the smaller rises among those with a titer > or =
      1:16. Based on the attack survey conducted separately, the vaccine efficacy on
      influenza-like illnesses with fever < or = 37 degrees C and > or = 37.5 degrees C
      was calculated to be 16% (95% confidence interval: -66% to 57%) and 37% (-55% to
      74%), respectively.

PMID- 9032888
TI  - Protection of cattle against Fasciola hepatica infection by vaccination with
      glutathione S-transferase.
AB  - Glutathione S-transferase (GST) from the liver fluke Fasciola hepatica was
      assessed as a vaccine immunogen in cattle in a number of immunological adjuvants.
      Significant reductions in fluke burdens (49-69%) were only observed in cattle
      vaccinated with GST in Quil Alsqualene Montanide (SM) and PLG microspheres in SM
      but there was no correlation between anti-GST IgG titres and protection. In
      separate experiments, animals vaccinated with GST in Quil AlSM were still
      significantly protected (48%, P < 0.05) 6 months after boosting and no
      significant differences in protection were seen when the metacercarial challenge
      was given over 1 month instead of as a single bolus. Inhibition of GST enzyme
      activity in vitro by cattle antisera did not correlate with reduced fluke
      burdens.

PMID- 9032889
TI  - Local and systemic immune response to a microencapsulated sub-unit vaccine for
      plague.
AB  - Microencapsulated Fl and V sub-unit antigens of Yersinia pestis were used to
      immunize mice intraperitoneally with a combination of 25 micrograms of each of
      the microencapsulated sub-units. The combined microsphere formulation induced
      both mucosal and systemic immunity. There was an additive effect in combining sub
      units and the protection afforded by the combined microencapsulated antigens was
      superior to that provided by the administration of any single encapsulated
      antigen and by the existing whole cell vaccine. The protective efficacy of the
      combined microencapsulated sub-units was further enhanced by co-administering
      cholera toxin B sub-unit. Microencapsulation of the sub-units offered advantages
      which included depot release of the vaccine in vivo and the facilitation of oral,
      intranasal or inhalational delivery. Therefore, immunization with
      microencapsulated sub-unit antigens was an effective means of generating humoral
      and cellular responses which endowed protective immunity.

PMID- 9032890
TI  - Evaluation of the safety, reactogenicity and immunogenicity of three recombinant
      outer surface protein (OspA) lyme vaccines in healthy adults.
AB  - The safety, reactogenicity and immunogenicity of three candidate Lyme vaccines
      based on recombinant outer surface protein (OspA) presented in either lipidated
      or unlipidated forms, were assessed in 300 seronegative volunteers. Subjects
      received three doses of one of the three formulations at monthly intervals and
      were evaluated for antibody levels and the presence of symptoms after each dose.
      All formulations proved to be safe, the majority of local reactions being
      reported as mild, and all general symptoms were perceived to be either-mild or
      moderate in intensity. No subject refused a subsequent vaccine dose. All subjects
      were tested for both anti-OspA IgG and LA-2 equivalent antibodies up until day
      84. All three vaccines induced an immune response but subjects who received
      lipoprotein OspA had the highest anti-OspA IgG and LA-2 equivalent GMTs after
      each dose and this was also true for the subset of subjects tested on day 180.
      The lipoprotein OspA group also had the largest number of subjects who remained
      seropositive for anti-OspA IgG antibodies. As the lipoprotein formulation
      produced the strongest immune response, with symptoms which were acceptable to
      all the vaccinees, we suggest further development of this vaccine.

PMID- 9032891
TI  - Single shot with tetanus toxoid in biodegradable microspheres protects mice
      despite acid-induced denaturation of the antigen.
AB  - Tetanus toxoid encapsulated in microspheres consisting of biodegradable
      polyesters, prepared by four different manufacturers were evaluated with respect
      to antigenic load, in vitro release pattern, antigen integrity and
      immunogenicity. In vitro release studies over periods up to 140 days indicated
      that only during the first days tetanus toxoid was released. Although some
      preparations were designed to release their antigen content in a pulsatile
      manner, this was never observed in vitro. A single immunization with 0.3 Lf
      tetanus toxoid in microspheres induced substantial humoral responses, in most
      cases higher than one immunization with plain tetanus toxoid, sometimes higher
      than one dose of alum-adsorbed toxoid but always lower than booster
      immunizations. It is shown that the moderate (no booster effect) performance of
      the microsphere preparations is probably due to acid induced denaturation of the
      antigen. Despite this drawback, protection level in mice after challenge with 50
      LD50 1 year after one immunization with microspheres was, on average,
      substantially higher than mice receiving plain tetanus toxoid.

PMID- 9032892
TI  - Diphtheria antitoxin titres six years after basic immunization of adults.
AB  - Diphtheria antitoxin titres were analysed in 160 adults (median age 59 years,
      range 34-70), who completed basic vaccination with three doses of 7.5 Lf or 15 Lf
      of diphtheria toxoid (D) in a previous vaccination trial in 1987, in serum
      samples drawn 6 years later. The median titre had decreased from 3.2 IU ml-1 in
      the post vaccination samples to 0.2 IU ml-1 after 6 years in the 15 Lf group and
      0.1 IU ml-1 in the 7.5 Lf group. An antitoxin titre of < 0.01 IU ml-1, a level
      usually considered to give no safe protection, was found in 21/73 (29%)
      individuals, who had received 7.5 Lf and in 12 of 87 (14%), who received 15 Lf
      diphtheria toxoid (P < 0.05). In the original study, the vaccinees were enrolled
      as unimmunized based on their own vaccination histories, but many participants
      had serological evidence of previous immunization. In the subgroup of 48 truly
      non-immune participants, i.e. without prevaccination titres and without booster
      response after the first injection, 46% (32% in the 15 Lf group and 58% in the
      7.5 Lf group) had antitoxin levels of < 0.01 IU ml-1 6 years after basic
      vaccination. Therefore, individuals who have received basic vaccination with
      three doses of diphtheria toxoid need at least one booster injection 5-10 years
      later.

PMID- 9032893
TI  - Identification of mutations contributing to the reduced virulence of a modified
      strain of respiratory syncytial virus.
AB  - The nucleotide sequences of the genome of the RSS-2 wild type strain of
      respiratory syncytial (RS) virus, which is known to induce upper respiratory
      tract infection in adults, and that of the attenuated ts1C candidate vaccine
      derived from it by three cycles of mutagenesis and selection of temperature
      sensitive (ts) mutants, have been determined. Comparison of the sequences has
      located the genetic changes which contribute to the reduced pathogenicity in
      adults of the candidate vaccine. Thirty-seven nucleotide changes distinguish the
      wild type and ts1C, 13 of which confer amino acid substitutions; no mutations are
      present in extragenic regions. Partial nucleotide sequencing of the genomes of
      the first stage ts mutant (ts1A) and the second stage ts mutant (ts1B), which
      were intermediates in the derivation of the third stage mutant ts1C, established
      that five mutations resulting in amino acid substitutions had been induced in the
      first cycle of mutagenesis, one in the second cycle, and seven in the third
      cycle. The unique mutation differentiating ts1B from ts1A substitutes an alanine
      for a threonine at residue 736 in the polymerase (L) protein. The occurrence of a
      mutation in ts1C inducing substitution of a phenylalanine for a serine residue at
      an adjacent site (731) suggests that mutations in this region of the polymerase
      can have significant attenuating effects. The data suggest also that a mutation
      in the F gene may contribute to the attenuated phenotype.

PMID- 9032894
TI  - Low-dose intramuscular revaccination against hepatitis B.
AB  - Little research has been conducted on low booster doses in adults and only
      intradermal (i.d.) inoculation has been used with high rates of adverse reactions
      among subjects i.d. revaccinated. The present study compare a low intramuscular
      dose of recombinant hepatitis B vaccine with standard 20 micrograms
      revaccination. We studied 122 hospital workers 5 years after vaccination with
      recombinant hepatitis B vaccine who were randomly allocated to either the study
      group or control group. The study group received revaccination with 0.1 ml (2
      micrograms) of recombinant hepatitis B vaccine and the control group 1.0 ml (20
      micrograms). Two micrograms of i.m. vaccine was as effective as 20 micrograms
      i.m. in inducing antibody response and the antibody decrease after revaccination
      between groups was similar (P > 0.05) and independent of the initial
      concentration of anti-HBs after revaccination and dose (20 micrograms vs 2
      micrograms). In conclusion, in subjects who had received a standard hepatitis B
      vaccination and had showed anti-HBs titres higher or equal than 10 mIU ml-1 after
      vaccination, low i.m. booster doses of vaccine give a rapid anamestic response
      similar to standard revaccination with less adversal reactions than low i.d.
      administered dose and would be an effective and less expensive alternative to
      revaccination against HBV of populations at high risk.

PMID- 9032895
TI  - Antibody responses and protection in mice immunized orally against influenza
      virus.
AB  - Antibody responses and protection were studied in BALB/c mice immunized orally
      with formalin-inactivated influenza viruses (A/PR/8/34) combined with cholera
      toxin B subunit as adjuvant. Influenza virus-specific IgA as well as IgG antibody
      responses were induced in the mice, depending on the oral dosage frequency. The
      oral immunization by multiple doses resulted in reduction of viral replication in
      the nose and prevention of development of infection in the lung after intranasal
      (i.n.) challenge. The protective effect in the nose was thought to be related to
      the nasal IgA antibody response. The oral immunization was, however, less
      efficient for induction of the IgA antibody response and protection in the nose,
      compared with an i.n. immunization. The oral immunization following subcutaneous
      priming led to the complete protection in the nose, accompanied-by a prompt local
      IgA antibody response.

PMID- 9032896
TI  - Recombinant feline herpesvirus type 1 expressing immunogenic proteins inducible
      virus neutralizing antibody against feline calicivirus in cats.
AB  - In this study, an entire open reading frame encoding the capsid protein of feline
      calicivirus (FCV) F4 strain was inserted into the deletion locus (SmaI site) of
      the thymidine kinase (TK) deficient mutant (C7301dlTK) of feline herpesvirus type
      1 (FHV-1) and the resulting recombinant virus was designated as C7301dlTK-Cap.
      Expression of the FCV antigens by C7301dlTK-Cap was confirmed by indirect
      immunofluorescence assay and immunoblot analysis. To assess whether the
      recombinant virus can induce virus neutralizing (VN) antibody against FCV in the
      natural host, three cats were inoculated intranasally and orally with C7301dlTK
      Cap (two cats) or C7301dlTK (one cat). As a result, sera collected from cats
      inoculated with the C7301dlTK-Cap possessed VN antibody against FCV. This
      recombinant virus is expected as a new polyvalent recombinant vaccine against FHV
      1 and FCV infections.

PMID- 9032897
TI  - Cytotoxic T cell induction with ratchet peptide libraries.
AB  - Immunization with synthetic peptides are used to induce cytotoxic T cell (CTL)
      responses in vivo. However, CTL peptide vaccines require the use of multiple
      peptides to overcome genetic diversity associated with MHC restriction, and prior
      epitope identification from the chosen protein template. We describe here a
      method whereby all nonamer sequences from a longer template can be synthesized
      simultaneously in a ratchet peptide library (RPL) covering all potential epitopes
      within a protein. We synthesized an RPL based on a template sequence from the
      Plasmodium berghei circumsporozoite (CS) protein (CSRPL). Using a lipopeptide
      formulation we immunized mice i.p. with the CSRPL and elicited CS specific CTL,
      which recognized the CS252-260 H-2Kd restricted CTL epitope.

PMID- 9032898
TI  - Adjuvant effect of biodegradable poly(DL-lactic acid) granules capable for
      antigen release following intraperitoneal injection.
AB  - Ovalbumin (OVA)-containing poly(DL-lactic acid) (PDLLA) granules were prepared
      with different conditions. Following the intraperitoneal (i.p.) immunization of
      mice with the granules containing OVA, production of anti-OVA IgG antibody in the
      mouse serum was investigated. The i.p. injection of the granules induced a strong
      antibody production compared with that of free OVA, irrespective of the amount of
      OVA released for initial a few weeks and the period of OVA release. The serum
      level of IgG antibody induced by the granules was retained at a high level over
      16 weeks although the period of OVA release and the amount of OVA released
      initially were different from each other. The initial OVA release for a few weeks
      was essential to induce the enhanced antibody production. Comparison of mice
      immunization by granules with different OVA loadings but at a similar dose
      revealed that antibody level was higher for the granules with lower loading than
      for those with the higher loading. However, when the granules were injected after
      encapsulation into a poly(vinyl alcohol) (PVA) hydrogel tube, the difference in
      their antibody level became insignificant. Because PVA encapsulation did not
      affect the OVA release profile, this finding indicates that the injection amount
      of the granules seems to have influenced the antibody production. We conclude
      that the release profile of OVA is not always a key factor to enhance the
      antibody production of OVA-containing granules so far as the initial OVA
      controlled release is achieved.

PMID- 9032899
TI  - Size effect on systemic and mucosal immune responses induced by oral
      administration of biodegradable microspheres.
AB  - Induction of systemic and mucosal immune responses following oral administration
      of biodegradable poly(D,L-lactic acid) (PDLLA) microspheres containing a model
      antigen, ovalbunin (OVA) was studied using microspheres with different average
      diameters of 0.6, 1.0, 4.0, 7.0, 11.0, 15.0, 21.0, and 26.0 microns. They were
      prepared from double emulsion with the solvent evaporation method, followed by
      size fractionation on counterflow elutriation. OVA was released from the
      microspheres in vitro over 80 days, irrespective of their size. Production of the
      serum anti-OVA IgG antibody and secretory OVA-specific IgA antibody in the mice
      gut was assessed following the oral administration of PDLLA microspheres
      containing OVA. Microspheres with a diameter of 4.0 microns enhanced the serum
      antibody in contrast with that of free OVA, but were not effective in inducing
      the gut secretion of IgA antibody. On the other hand, OVA-containing microspheres
      with a diameter of 7.0 microns enhanced IgA secretion to a significant extent
      compared with free OVA, whereas those with 26.0 microns in diameter were
      ineffective. Body distribution study revealed that the amount of microspheres
      taken up into Peyer's patches (PP) increased with the increasing size up to 11.0
      microns, thereafter decreased, and finally became zero when their diameters were
      21.0 microns or larger. The microspheres taken up into PP were translocated to
      the spleen, but no microspheres were noticed in the spleen when the size was
      larger than 5 microns. After being taken up inot PP, microspheres < 5 microns in
      diameter seemed to be transported to the spleen, a systemic lymphoid tissue,
      where the released antigen stimulated a serum antibody response, but larger
      microspheres probably remained at PP without being translocated to the spleen
      over the course of their antigen release, leading to induction of IgA secretion.
      It was concluded that the body distribution pattern of microspheres following the
      PP uptake was a key factor to regulate the induction of systemic and mucosal
      immune responses.

PMID- 9032900
TI  - Murine cytomegalovirus inactivated by sodium periodate is innocuous and
      immunogenic in mice and protects them against death and infection.
AB  - Sodium periodate (10 mM, 4 degrees C) inactivated murine cytomegalovirus (MCMV)
      very rapidly (loss of 2 to 3 log of viral infectivity per minute). Periodate
      treated MCMV (PI-MCMV) was shown to be innocuous in mice, as determined by the
      inability of the virus to replicate. PI-MCMV induced a strong humoral immune
      response, with a high level of neutralizing antibodies. Mice immunized with PI
      MCMV were protected against death and infection, when a lethal challenge with the
      virulent virus was administered 3 weeks after immunization and from death but not
      infection when virulent virus was administered at 3 months. Finally, no
      reactivation of potentially latent challenge virus (sublethal dose at 3 weeks)
      was observed in animals immunosuppressed at 6 months after immunization. Taken
      together, these results suggest that periodate could serve as an inactivating
      agent to prepare killed vaccines.

PMID- 9032901
TI  - Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the
      evaluation of Marek's disease virus-induced immunosuppression in chickens.
AB  - Antigen-specific lymphoproliferative responses were examined in chickens
      following immunization with tetanus toxoid (Ttx). The immune competence of
      chickens was assessed by mitogen assay utilizing phytohemagglutinin (PHA)
      stimulation and Ttx-specific antigen proliferation assay (Ttx-APA). Immune spleen
      cells but not peripheral blood leucocytes demonstrated specific proliferation
      following stimulation in vitro in a Ttx-APA. In this study, we examined firstly
      the effects of Marek's disease (MD)-associated immunosuppression on specific
      immune responses. The humoral and cell-mediated immune responses were monitored
      by enzyme-linked immunosorbent assay (ELISA) and Ttx-APA, respectively. Secondly,
      we examined if vaccination against MD using a conventional herpesvirus of turkeys
      (HVT) vaccine and two recombinant HVT (rHVT) vaccines would affect the
      development of Ttx-specific immune responses. The rHVT vaccines used in this
      study included two constructs: one expressing both Newcastle disease virus (NDV)
      and MD virus (MDV) genes (HVT/NDV/MDV), and another expressing only MDV genes
      (HVT/MDV). The mitogenic responses of spleen cells of the vaccinated chickens
      were inconsistent allowing no definitive conclusions about vaccinal
      immunosuppression. The results of the Ttx-APA indicated that Ttx-specific
      lymphoproliferative responses provide a meaningful measure of immunosuppression.
      The MDV-induced immunosuppression resulted in the inhibition of Ttx-specific
      lymphoproliferation in vitro. Both HVT and rHVT vaccines were not
      immunosuppressive as indicated by the development of normal Ttx-specific
      lymphoproliferative responses in chickens. These results indicate that
      vaccination against MD results not only in the prevention of tumor formation but
      also protection from possible virus-induced immunosuppression.

PMID- 9032902
TI  - Immune responses following cocktails of inactivated measles vaccine and Arachis
      hypogaea L. (groundnut) or Cocos nucifera L. (coconut) oils adjuvant.
AB  - Haemagglutination inhibition (HAI), geometric mean titre (GMT) and lymphocyte
      transformation test (LTT) were measured following inoculation of Erythrocebus
      patas with inactivated measles vaccine (IMV) and oils of Arachis hypogaea L (GO),
      Cocos nucifera L (CO), Freund's complete and incomplete adjuvants (FCA, FIA). The
      GMT of HAI were: GO + IMV = 8.50 +/- 4.15: CO + IMV = 8.08 +/- 4.03; FCA + IMV =
      7.67 +/- 4.08. FIA + IMV = 7.08 +/- 4.08 compared with controls of live measles
      vaccine (LMV) = 7.33 +/- 4.33 and IMV = 4.33 +/- 4.56. The mean stimulation ratio
      (SR) of lymphocyte transformation data were: GO + IMV = 109 69; CO + IMV = 58.47;
      FCA + IMV = 55.81. FIA + IMV = 55.48; LMV = 94.73; IMV = 55.64. The results when
      compared by a two-way multiple pairwise comparison of Tuskey's procedure at alpha
      = 0.05 showed that HAI antibody titres were not significantly different in all
      the groups under investigation. The lymphocyte transformation data for GO + IMV
      and LMV were identical but significantly different from the other groups. The
      study suggests that the oils under investigation, particularly the GO oil should
      be considered as an adjuvant with IMV after extensive study in humans; since it
      stimulated cellular immune response comparable to that of LMV. This is a
      promising alternative to the use of LMV in the tropical developing countries with
      poor storage facilities.

PMID- 9032903
TI  - Expression and secretion of the S2 subunit of pertussis toxin in Bacillus brevis.
AB  - We have been trying to develop a mass production system for each of the subunits
      (S2, S3, S4, S5) of the pertussis toxin B oligomer (PTB) by using a Bacillus
      brevis-pNU212 system. In consequence a moderately efficient expression-secretion
      system for S2 was constructed by fusing the mature S2 gene from Bordetella
      pertussis Tohama with the signal-peptide coding region of pNU212 and by
      introducing the plasmid pNU212-S2 into B. brevis HPD31 by electroporation. The
      clone producing S2 secreted about 70 mg of recombinant S2 (rS2) per liter of PY
      erythromycin medium after 5 days incubation at 37 degrees C. The rS2 purified by
      an ammonium sulfate fractionation at 30-50% saturation and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) was identical to the native S2 in
      respect to the molecular weight determined by SDS-PAGE and the amino terminal
      amino acid sequence. The nucleotide sequence of the S2 gene in B. pertussis
      Tohama inserted into pNU212 was identical with that of the S2 gene in other
      virulent B. pertussis strains except that an adenine at position 52 of the latter
      was replaced by a guanine in the former, causing an amino acid substitution
      (glycine in the former for serine in the latter) at position 18.

PMID- 9032904
TI  - New scientific developments towards an AIDS vaccine: report on a workshop
      organized by EU programme EVA entitled Novel approaches to AIDS vaccine
      development held at the Institut Pasteur, Paris. 16-17 November 1995.

PMID- 9032905
TI  - Is the test for abnormal toxicity, general safety or innocuity necessary for
      vaccines?

PMID- 9032906
TI  - Advisory committee urges caution on xenotransplantation.

PMID- 9032907
TI  - E coli outbreak prompts tightening of food safety procedures.

PMID- 9032908
TI  - Naturally occurring persistent and asymptomatic infection of the guttural pouches
      of horses with Streptococcus equi.
AB  - During an outbreak of strangles on a farm with approximately 1500 horses, the
      spread of Streptococcus equi infection was monitored by repeated nasopharyngeal
      swabbing and culture. In order to control the infection and prevent new
      introductions of strangles on to the premises, a system of quarantine and
      swabbing of cases and all incoming animals was instituted. Long-term carriage of
      the organism was detected in four clinically healthy convalescent animals, and in
      two of 350 new ponies; it persisted for between seven and 39 months, but it was
      detected only intermittently by the culture of swabs which was a much less
      sensitive method than the culture of guttural pouch lavages taken by endoscopy
      (45 per cent v 88 per cent sensitivity, respectively, for any single sample).
      Repeated swabs were often negative for several weeks between positive samples.
      Nonetheless, in all but one of the long-term carriers, S equi was detected by
      culture of repeated swabs taken over a period of less than two to three months.
      Infection was detected unilaterally in the guttural pouches of five of the
      carriers and was accompanied by large numbers of neutrophils in the lavage
      samples whether or not there was empyema. Abnormalities of the affected guttural
      pouches were detectable by radiography but only after the instillation of
      contrast medium. The study indicated that clinically healthy long-term carriers
      of S equi present a serious risk of spreading strangles, particularly because
      they may be detected only by repeated nasopharyngeal swabbing over two to three
      months.

PMID- 9032909
TI  - Probability of detecting antibodies to bovine herpesvirus 1 in bulk milk after
      the introduction of a positive animal on to a negative farm.
AB  - The purpose of this study was to assess the probability that the introduction of
      one or more bovine herpesvirus 1 (BHV-1)-seropositive animals would result in the
      bulk milk of a clean herd becoming BHV-1-positive. Probability calculations
      (stochastic and deterministic) were based on the distribution of the log(titre)
      of 828 positive animals and the daily milk production of the herds and of the
      individual cows. They showed that the probability in average sized herds of 45
      dairy cows is only between 10 and 25 per cent and that even in small herds of 25
      cows the introduction of a positive animal would go undetected in the majority of
      cases. It is concluded that if the bulk milk has become BHV-1-positive it is most
      likely that the infection has spread.

PMID- 9032910
TI  - Ultrasonographic examination of the abomasum of 50 cows.
AB  - The purpose of this study was to determine the position, appearance and
      dimensions of the abomasum of 50 healthy cows by ultrasonography. The ventral
      abdominal region caudal to the xiphoid process was examined with a 3.5 MHz linear
      transducer. The abomasum could be visualised from both sides and from the ventral
      midline of 47 of the cows. The abomasum could be clearly differentiated from
      adjacent organs because of its contents, which appeared as a heterogeneous,
      moderately echogenic structure with echogenic stippling. However, the wall of the
      abomasum appeared, if at all, as a narrow echogenic line. Parts of the abomasal
      folds were visible occasionally as echogenic structures within the abomasum. Slow
      movement of the feed in the abomasum was also often visualised. The pylorus was
      positively identified in only one cow. The cranial margin of the abomasum was
      situated up to 15 cm caudal to the xiphoid process. The abomasum was between 7.4
      and 42.9 cm long, and its maximal extent, measured from the ventral midline to
      the left, was from 5.0 to 26.0 cm in the cranial region and from 5.0 to 16.0 cm
      in the caudal region. From the ventral midline to the right, it was from 5.0 to
      33.0 cm in the cranial region and from 28.0 to 36.0 cm in the caudal region. The
      minimal dorsoventral dimension of the abomasum ranged from 0.7 to 7.2 cm, and its
      maximal dorsoventral dimension ranged from 3.6 to 11.1 cm.

PMID- 9032911
TI  - Evidence of infection with feline immunodeficiency virus among Danish cats
      between 1970 and 1974.

PMID- 9032913
TI  - Vaccination of cage and aviary birds against Newcastle disease.

PMID- 9032912
TI  - Ovarian hypoplasia in Lleyn ewes.

PMID- 9032914
TI  - Artificial insemination of horses.

PMID- 9032915
TI  - Avoparcin ban.

PMID- 9032916
TI  - When to spay dogs and cats.

PMID- 9032917
TI  - Urinary incontinence in cats.

PMID- 9032931
TI  - The production of recombinant glycoproteins with special reference to simple
      eukaryotes including Dictyostelium discoideum.
AB  - Because many recombinantly produced proteins require post-translational
      modification to be properly folded and active, there is a new emphasis on
      eukaryotic expression systems. Dictyostelium discoideum is a well studied
      eukaryotic model organism for the investigation of key questions in molecular and
      cell biology. More recently D. discoideum was successfully used as a system for
      recombinant glycoprotein production. The vegetative amoebae are easy and
      inexpensive to grow either in axenic culture or on Gram-negative bacteria.
      Reliable and uncomplicated transformation systems are also well established. This
      organism harbours the machinery to perform post-translational modifications such
      as phosphorylation, acylation, formation of glycosylphosphatidylinositol anchors
      and more importantly N- and O-linked glycosylation. This review provides an
      overview of glycosylation in different expression systems and focuses on
      glycosylation in D. discoideum.

PMID- 9032932
TI  - Immunoglobulin stability.

PMID- 9032933
TI  - Stability assessment of lyophilized intravenous immunoglobulin after
      reconstitution in glass containers and poly(vinyl chloride) bags.
AB  - Human intravenous immunoglobulin (IGIV) has been in use for the past 20 years.
      This biological product is commonly provided in liquid or lyophilized dosage
      form. When the lyophilized product is rehydrated, it is usually administered
      within 2-3 h from time of complete dissolution. While this practice is advisable
      whenever possible, occasionally the patient or care-giver may need to delay the
      infusion. Hence, a study of the stability of lyophilized IGIV after
      reconstitution with water for injection was conducted. The reconstituted product
      was stored either in its original glass container or pooled into poly(vinyl
      chloride) (PVC) bags. The effect of extended storage on the active ingredient
      (IgG), excipients (glucose, albumin) and extractables [sodium from glass vials,
      and di-(2-ethyl-hexyl) phthalate and cyclohexanone from PVC bags] was evaluated.
      The stability of the active ingredient was evaluated by physico-chemical tests
      (molecularsize distribution, pH, appearance, total protein), monitoring titres of
      a specific antibody (hepatitis B surface antigen) and an antibody functional test
      (bacterial opsonization). To evaluate the risk of microbial contamination during
      reconstitution and pooling procedures, sterility, pyrogen and animal-safety tests
      were included in the protocol. The potential of IgG polymerizing in solution
      during storage and subsequent complement activation was evaluated by assaying for
      non-specific binding of complement (anti-complement activity). Results show that
      aseptically reconstituted IGIV is stable and remains sterile up to 48 h at 5
      degrees C. The reconstituted product was also found to be stable at room
      temperature (25 degrees C) up to 12 h.

PMID- 9032934
TI  - Stability and chemical modification of xylanase from Aspergillus sp. (2M1
      strain).
AB  - The 2M1 strain of Aspergillus sp., which showed high extracellular xylanolytic
      activities in a pre-screening, was studied. Oat-spelt, birch, eucalyptus and pine
      xylans were used as xylanolytic inductors. The following activities were found at
      50 degrees C in the presence of 1% xylan: 120 units/ml (oat-spelt xylan), 132
      units/ml (birch xylan), 107 units/ml (eucalyptus xylan), 67 units/ml (pine xylan)
      and 137 units/ml (larch-wood xylan). Xylanase induced by pine xylan exhibited a
      higher stability than those induced by the other xylans. The stability was
      improved by addition of glycerol. In the crude extract, reagents which were found
      to affect xylanase activity were 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide
      for amidation of carboxylic groups and N-bromosuccinimide at a concentration of
      0.5 mM for indole oxidation. Methylene Blue, butane-2,3-dione, N-acetylimidazole,
      chloramine-T and iodoacetate had little effect on the enzyme activity (more than
      97% of the original activity remained).

PMID- 9032935
TI  - Studies of DEAE-dextran-mediated gene transfer.
AB  - DEAE-dextran-mediated gene transfer was studied for the introduction of pSV2neo
      DNA into Fisher-rat 3T3 (FR3T3) cells. Zeta (zeta) potentials of the DEAE-dextran
      DNA complexes and FR3T3 cells were found to be dependent on the concentration of
      DEAE-dextran in the medium. The maximum transfection efficiency occurred at a
      DEAE-dextran/DNA ratio of 50:1 or thereabouts. The interaction between DNA and
      cells is determined by the adsorption process. The results obtained, along with
      the correlation between the kinetic adsorption behaviour of 3H-labelled DNA and
      the transfection efficiency, indicated that adsorption of DEAE-dextran-DNA
      complexes to the negatively charged cell surfaces, due to electrostatic and
      dispersion attraction, plays the decisive role in determining the DNA
      transfection efficiencies.

PMID- 9032936
TI  - Glycine-induced extracellular secretion of a recombinant cytochrome expressed in
      Escherichia coli.
AB  - The effect of each of 20 different amino acid supplements to the growth medium of
      Escherichia coli on the extracellular release of a periplasmic recombinant
      cytochrome b5 was investigated. Only glycine, and to a lesser extent histidine,
      stimulated the synthesis of secretory cytochrome b5, as well as its discharge
      into the medium. Extracellular amounts of cytochrome b5 accrued with increasing
      concentrations of exogenous glycine and duration of the culture period, in spite
      of the fact that increasing glycine in the medium progressively inhibited cell
      growth. For example, 1% medium glycine caused a 50% reduction in bacterial
      growth, but doubled the periplasmic pool of cytochrome b5 to over 25 micrograms
      of cytochrome b5/ml of culture at 24 h, a period during which almost all of
      cellular haemoprotein pool was turned over into the medium. A comparative study
      of the exportable form of cytochrome b5 with a (non-secretory) cytoplasmic
      resident counterpart indicated that the periplasmic cytochrome b5 content was
      selectively discharged into the medium when less than 1% glycine was present,
      but, at higher doses, a significant proportion of the additional extracellular
      haemoprotein was derived from cell lysis. Optimal level of periplasmic discharge
      of the cytochrome required both active protein synthesis and the presence of a
      glycine supplement in the medium from the onset of bacterial growth. Phase
      contrast and scanning electron microsocopy of glycine-grown Escherichia coli
      showed that the cells had a 3-7-fold enlarged "eyeball' spheroidal morphology,
      with a condensed pericircular cytoplasm. The bulk of the volume in such
      hypertrophied cells consisted of the periplasm; this was reflected by the
      progressively lowered buoyancy of E. coli cultured with increasing amounts of
      glycine. The fragility of such cells was apparent by their marked sensitivity to
      lysis at glycine concentrations above 1%. We conclude that supplementation of E.
      coli cultures with moderate amounts of glycine substantially stimulates the
      synthesis of exportable proteins and further enhances their yield by discharge
      into the growth medium.

PMID- 9032937
TI  - High-level secretion in Pichia pastoris and biochemical characterization of the
      recombinant kringle 2 domain of tissue-type plasminogen activator.
AB  - The kringle 2 (K2) domain of tissue-type plasminogen activator (tPA) has been
      expressed in Pichia pastoris cell lines GSI 15 and KM71. This construct contained
      a hexahistidine sequence at the C-terminus of the kringle to aid in purification
      by immobilized metalion-affinity chromatography. The exact amino acid sequence of
      the isolated kringle was EAEAYV-[K2tPA]SR(H)6, where [K2tPA] represents amino
      acid sequence residues C1-C82 of the kringle domain (residues 180-261 of tPA).
      The clones of the yeast transformants provided large amounts of the recombinant
      (r)-[K2tPA]-containing polypeptide at levels that allowed ready purification of
      several hundred mg from shake flasks and near-gram levels from a high-biomass
      fermenter. Purification of the kringle domain directly from cell-conditioned
      media was accomplished in a single step by either immobilized Ni(+)-affinity
      chromatography or lysine-Sepharose affinity chromatography. N-linked glycans were
      present on approx. 30% of this yeast-expressed material, at N5 of the kringle
      (corresponds to N11 of the particular construct, N184 of full-length tPA). The
      expressed recombinant kringle recognized a conformation-specific monoclonal
      antibody generated against tPA that is directed to the K2 domain of the protein,
      interacted properly with various omega-amino acid ligands, and showed signature
      conformational properties when studied by differential scanning calorimetry and
      high-resolution 1H-NMR. The results demonstrate that the P. pastoris system can
      be employed to obtain large amounts of secreted and properly folded kringle
      domains.

PMID- 9032938
TI  - Lithium inhibits growth in a murine neural precursor cell line.
AB  - The influence of lithium on cell growth and cell viability was studied in short
      term cultures of a neural precursor cell line (NT) developed from a murine
      teratocarcinoma. At very low concentrations ranging from 0.1 mM to 1 mM Li2CO3
      (equivalent to therapeutic blood concentrations) there was no difference between
      untreated and treated cultures. 10 mM lithium (Li+) was found to be toxic with
      33% of cell death, while there was inhibition of growth without cell death at
      concentrations of 2.5 mM and 5 mM of Li+. In experiments where 2.5 mM Li+ was
      added at the time of seeding, there was growth arrest on day 1 followed by
      recovery on day 2. Flow cytometric analysis revealed that cells treated with Li+
      were blocked in S phase. At 5 mM concentration of Li+, the recovery occurred on
      day 3 and the plating efficiency was significantly low. The ability to form
      colonies in soft agar was reduced at 2.5 mM and 5 mM concentrations of Li+ to an
      equal extent. Thus, Li+ has growth inhibitory as well as anchorage-independent
      growth reducing effects. The NT cell line therefore would be a good model system
      to study the mechanism of teratogenic effect of Li+.

PMID- 9032939
TI  - Synergistic antitumour activity of vitamins C and K3 against human prostate
      carcinoma cell lines.
AB  - Vitamins C, K3 (VC, VK3) and a VC/VK3 combination with a VC:VK3 ratio of 100:1
      were assayed for their antitumour activity against two human prostatic carcinoma
      cell lines. Co-administration of the vitamins enhanced the antitumour activity 5-
      to 20-fold even with a 1 h exposure time. While exogenous catalase destroyed the
      antitumour activity, hydrogen peroxide-induced lipid peroxidation was negligible.
      Analysis of cellular ATP and thiol levels as well as DNA and protein synthesis
      revealed: a transient increase in ATP production, a decrease in DNA synthesis, an
      increase in protein synthesis and a decrease in thiol levels. These results
      suggested that the increased cytotoxicity of the vitamin combination was due to
      redox cycling and increased oxidative stress.

PMID- 9032940
TI  - Presence of multiple centrioles and primary cilia during growth and early
      differentiation in the myoblast CO25 cell line.
AB  - CO25 cells, a mouse myoblast line, contain multiple centrioles and primary cilia.
      A most unusual feature has been the finding of large numbers of separate
      structures in single cells-up to a maximum of nine centrioles, six primary cilia,
      and 12 of both organelles together. Aberrant multipolar spindles were
      occasionally seen containing variable numbers of centrioles. This strongly
      suggests that cells containing supernumerary centrioles and cilia are lost during
      mitosis, and that additional centriolar structures are generated during each
      interphase. No change in centriole or primary cilium frequency was detected after
      inducing the differentiation of myoblasts into myotubes. However, a significant
      migration of these structures occurred from a perinuclear to a supranuclear
      position prior to and during the phase of myoblast elongation. This shift was not
      maintained during cell fusion, when a net migration back to the periphery was
      observed, suggesting that it may have some function in relation to cell
      elongation and the change in the pattern of microtubule distribution which occurs
      as part of the process.

PMID- 9032941
TI  - Basement membrane associated changes in the rat ventral prostate following
      castration.
AB  - This study focuses on the basement membrane associated modifications that take
      place after androgen blockade, by studying some of its main components, through
      histochemical, immuno-histochemical and Western blotting tests, and its
      ultrastructural aspects. It was demonstrated that laminin and collagen type IV
      remain associated with a thickened basement membrane and that there is an
      apparent increase in heparan sulfate content 21 days after castration.
      Ultrastructurally, basal lamina appeared extensively folded and pleated. It was
      also observed that detachment of epithelial cells is not dependent of basal
      lamina degradation and that the free basal lamina surfaces are folded by the
      action of adjacent cells. We have also observed some aspects of smooth muscle
      cell degeneration and death, that lead to modifications of the associated basal
      lamina. In this case, residual basal lamina also shows extensive folding. The
      results suggested that degradation of excess basement membrane does not occur or
      is a very slow process within the period examined, and that basement membrane is
      left re-organized but ultrastructurally and compositionally unaffected.

PMID- 9032942
TI  - Structural and functional roles of cytoskeletal proteins during repair of native
      guinea pig intestinal epithelium.
AB  - The cytoskeletal events that assist restitution of the native intestinal
      epithelium are poorly understood. To enhance our understanding of repair
      mechanisms in the native intestinal epithelium we assessed the functional role of
      actin and the temporal and spatial alterations in actin and villin that occur in
      native enterocytes migrating in response to injury. Using a well-characterized in
      vitro Ussing chamber model of native intestine epithelial restitution, the actin
      inhibitor cytochalasin D (CD) was applied to determine the functional importance
      of actin to restitution as assessed by sensitive electrophysiological means and
      structural techniques. Additionally we used phalloidin and indirect
      immunohistochemistry to localize and semiquantitate F-actin and villin in
      migrating cells during restitution. We report new data that shows that when
      cytoskeletal changes were impaired with CD, the epithelial monolayer was re
      established in fewer than 20% of CD-treated villi, cells bordering the epithelial
      defect did not assume the characteristic phenotype associated with migrating
      cells, and transepithelial resistance did not return to pre-injury levels. F
      actin and villin were present at the leading edge of the migrating cells,
      basolateral F-actin was decreased, and cytoplasmic villin was increased as
      determined by phalloidin and immunohistochemical methods. We conclude that in
      vitro repair of the native intestinal epithelium is functionally and structurally
      dependent on major changes in the cytoskeleton of cells involved in re
      establishing the epithelial monolayer over a complex extracellular matrix.

PMID- 9032943
TI  - Nitroxide reduction with ascorbic acid in spin labeled human plasma LDL and VLDL.
AB  - The LDL and VLDL were spin labeled with Tempo which partitions both in the
      aqueous and lipid phase. The ESR spectra were measured in the equilibrium state
      as well as during the reduction of the spin label with ascorbic acid. The
      kinetics of the concentration decay curves was parametrized with two
      exponentials. The theoretical simulation of the experimental spectra revealed a
      drastic linewidth narrowing in the VLDL samples exposed to the ascorbic acid.
      Since the transport properties of the specific monolayer are reflected in the
      observed reaction rates, the analysis of the fatty acid composition of
      phospholipids, triglycerides and cholesterol esters in LDL and VLDL was
      performed. It is concluded that different lipid packing at the surface of LDL and
      VLDL might be the consequence of different intermolecular forces between
      phospholipids and cholesterol. This finding was connected to the experimentally
      detected different reaction kinetics in LDL and VLDL as well as their different
      susceptibility to the ESR linebroadening effects during the nonequilibrium
      conditions of the spin label reduction with ascorbic acid.

PMID- 9032944
TI  - Beta-blockers inhibit the modification of low-density lipoproteins by sodium
      hypochlorite in vitro.
AB  - The effect of beta-blockers (alprenolol, oxprenolol, atenolol, acebutolol) and
      the non-steroidal anti-inflammatory drug, diclofenac, on modification of low
      density lipoproteins (LDL) by sodium hypochlorite (NaOCl) was investigated in
      vitro. Beta-blockers and diclofenac inhibit the formation of thiobarbituric acid
      reactive substances in LDL modified by NaOCl. Beta-blockers, but not diclofenac,
      inhibit the hypochlorite-induced aggregation of LDL which was determined by
      photon correlation spectroscopy. The intracellular accumulation of cholesterol
      esters in J774 macrophages is inhibited by addition of beta-blockers, but not
      diclofenac, to LDL prior to the addition of NaOCl. The modification inhibiting
      effect of beta-blockers is inversely correlated to the binding capabilities of
      these substances to LDL which were assessed by laser electrophoresis. Inhibition
      of LDL modification in vivo by beta-blockers may reduce the risk of
      atherosclerosis and, therefore, compensate for the cholesterol-raising effect of
      these drugs in human plasma.

PMID- 9032945
TI  - Enthalpy is a proper criterion for comparability of monolayer and bilayer
      studies: isobaric temperature scanning measurements on glycolipid monolayers.
AB  - The thermotropic behaviour of glycolipid monolayers has been studied by isobaric
      temperature scanning measurements to elucidate conditions under which monolayers
      exhibit thermodynamic and structural properties comparable to those observed in
      bilayers. A selection of synthetic, stereochemically pure, glyceroglycolipids
      with identical, ether-linked alkyl chains of 12, 14, or 16 CH2-groups has been
      investigated. The head groups of the glycolipids consisted of glucose, galactose,
      maltose, lactose or maltotriose moieties with beta-configuration of the
      glycosidic bond. These glycolipids were chosen to permit a quantitative
      characterization of three effects, (i) the role of the length of the aliphatic
      chains, (ii) the influence of the size of the head group, and (iii) the influence
      of the stereochemistry of the sugar moieties on the structure and stability of
      the monolayers. To probe the effects of stereochemical alterations in the
      glycerol moiety 2,3-O-ditetradecyl-1-O-beta-D-glucosyl-sn-glycerol (14-2,3-Glc)
      was compared with 1,2-O-ditetradecyl-3-O-beta-D-glucosyl-sn-glycerol (14-1,2
      Glc). It has been shown that in general several features of bilayers can be
      obtained from monolayer studies with reasonable accuracy, provided the proper
      parameters are chosen. The monolayer is stabilized by elongation of the aliphatic
      chains of the lipids and destabilized when the monosaccharide read groups is
      replaced by a di-, or trisaccharide, in a similar manner as in the bilayer. The
      stabilizing effect that has been observed in bilayer studies, when galactose
      instead of glucose is introduced as head group, has also been established in the
      monolayer studies. This stabilizing effect is even retained in the lipids having
      disaccharide head groups. On the basis of these monolayer studies in connection
      with WAXS and SAXS measurements on multilamellar systems, we suggest that
      identity of transition enthalpies of the chain melting L beta-L alpha transition
      is an appropriate criterion for estimating molecular areas and area changes of
      bilayers from monolayer measurements and vice versa. However, estimates of
      transition temperatures are poor using the enthalpy criterion. If identity of
      transition temperature is introduced as criterion, glycolipid monolayers must be
      compressed to about 43 +/- 3 mN m-1. Under these conditions the agreement between
      the calculated enthalpies and structural properties of monolayers and multilayers
      is poor. As a general conclusion it can be emphasized that for monolayer and
      bilayer systems of glycolipids there exists no such parameter as a universal
      pressure or a universal temperature that automatically renders monolayer data
      identical to bilayer data. Depending on which property (transition temperatures,
      transition enthalpies, lateral areas and transitional area changes) one wants to
      extrapolate from monolayer to bilayer different lateral pressures have to be
      applied.

PMID- 9032946
TI  - Cryo-TEM and NMR studies of a micelle-forming phosphoglucolipid from membranes of
      Acholeplasma laidlawii A and B.
AB  - The chemical structure of a phosphoglucolipid from the membrane of the bacterium
      Acholeplasma laidlawii strain B-PG9 has been determined by high resolution NMR to
      be 1,2-diacyl-3-O-[glycerophosphoryl-6-O-(alpha-D-glucopyranosyl-(1 -->2)-O-alpha
      D-glucopyranosyl)]-sn-glycerol (GPDGlcDAG). It was concluded that this lipid has
      exactly the same structure as one of the phosphoglucolipids from A. laidlawii
      strain A-EF22. By cryo transmission electron microscopy (cryo-TEM) and NMR
      diffusion techniques it was shown that, in highly diluted aqueous solutions, this
      membrane lipid forms long thread-like micelles in equilibrium with lipid
      vesicles. The cause of the occurrence of these different aggregates is discussed
      in terms of the varying molecular shapes of the lipid because of a heterogeneous
      composition of the acyl chains. A second membrane phosphoglucolipid from the
      bacterium, namely 1,2-diacyl-3-O-[glycerophosphoryl-6-O-(alpha-D- glucopyranosyl
      (1 -->2)-monoacylglycerophosphoryl-6-O-alpha-D-glucopyranosyl)]-sn-gl ycerol
      (MABGPDGlcDAG), was found to form only a lamellar liquid crystalline phase
      coexisting with water.

PMID- 9032947
TI  - Riverine barriers and gene flow in Amazonian saddle-back tamarins.
AB  - We describe patterns of genotypic and phenotypic variation in saddle-back tamarin
      (Saguinus fuscicollis) populations along the central and upper Rio Jurua, western
      Brazilian Amazonia. The genetic data are sequence haplotypes of the mitochondrial
      cytochrome b gene; phenotypic data are pelage colour variants that define sharply
      demarcated subspecies of this extremely variable tamarin species. We show that
      gene flow occurs between adjacent subspecies, but that this phenomenon is
      restricted to the headwater section of the river, which is consistent with
      expectations from the riverine barrier hypothesis. In this model, the major first
      order tributaries of the Amazon form effective barriers to dispersal, with
      between-bank gene flow limited to the narrowed sections of headwater streams and
      parallel divergence increasing along both banks from the headwaters to the mouth
      of a given river. In meandering rivers such as the Rio Jurua, we suggest passive
      transfer through river channel dynamics as the main mechanism permitting genetic
      contact between populations on opposite banks of the river. Finally, we argue
      that in the case of plant and animal species that are largely restricted to
      unflooded (terra firme) forests, such as tamarins, seasonally flooded (varzea)
      forest can operate as a critical additional barrier to between-bank gene flow.

PMID- 9032948
TI  - Humeral head shape as an indicator of locomotor behavior in extant strepsirhines
      and Eocene adapids.
AB  - Postcranial material from Notharctus, Smilodectes and Cantius is abundant and
      well studied, but debate continues over whether the locomotor repertoire of these
      animals included a substantial component of vertical leaping. Here, the shape of
      the humeral head of 11 genera of extant strepsirhines, Notharctus, Smilodectes
      and Cantius was quantified using serial mediolateral and proximodistal contours.
      Univariate and multivariate analyses of these data show that vertically leaping
      strepsirhines have a distally relatively high narrow humeral head compared to
      arboreal quadrupeds and it places Notharctus and Smilodectes in a group with
      Hapalemur griseus, while Cantius is grouped with Eulemur macaco, suggesting that
      a quadrupedal form preceded the appearance of vertical leaping.

PMID- 9032949
TI  - Paternity discrimination in four prosimian species by the random amplified
      polymorphic DNA method.

PMID- 9032950
TI  - Quantitative and qualitative analysis of MDMA, MDEA, MA and amphetamine in urine
      by headspace/solid phase micro-extraction (SPME) and GC/MS.
AB  - The results of qualitative and quantitative analysis of some amphetamines and
      their analogs isolated from urine samples by solid phase micro-extraction with
      polydimethylsiloxane fibers are reported. The analytical method employed was gas
      chromatography/mass spectrometry of head space samples.

PMID- 9032951
TI  - Increasing DNA extraction yield from saliva stains with a modified Chelex method.
AB  - Recovery, preservation and analysis of body fluid stains is an important aspect
      of forensic science. PCR-based typing of DNA extracted from recovered stains is
      often a crucial method to identify a perpetrator or exclude an innocent suspect.
      This paper reports an improved method of extracting genomic DNA from saliva
      stains deposited on human skin in simulated bite mark situations. Results of
      organic (phenol-chloroform) extraction and Chelex extraction were compared to a
      modified Chelex method developed by the authors. Modifications include pre
      extraction preparation with proteinase K and incubations at 56 degrees C and 100
      degrees C plus microconcentration of the solution. Quantification results using
      the classical Chelex extraction method showed that 31.9 +/- 4.22% of the
      deposited DNA was recovered, but using the modified Chelex extraction method DNA
      recovery was increased to 47.7 +/- 6.90%. The quantity and quality of extracted
      DNA was shown to be adequate for PCR-based typing at two STR loci.

PMID- 9032952
TI  - Cocaine in hair, saliva, skin swabs, and urine of cocaine users' children.
AB  - The concentrations of cocaine and benzoylecgonine (BE) in the hair, saliva, skin
      secretions, and urine samples of cocaine-using mothers, their children, and other
      adults living in the same environment were compared. Subjects were screened from
      urban cocaine dependence treatment patients. Drug using adults had mean hair
      concentrations of 2.4 ng cocaine/mg hair (range = 0-12.2, sigma = 3.1, 15/16
      positive) and 0.39 ng BE/mg hair (range = 0-1.9, sigma = 0.62), compared with
      children's mean hair concentrations of 2.4 ng cocaine/mg of hair (range = 0-14.4,
      sigma = 3.8, 22/24 positive) and 0.74 ng benzoylecgonine/mg hair (range = 0-5.4
      sigma = 1.3). None of the children's urine specimens (0/22) were positive above
      300 ng BE/ml. In contrast, 3/16 adult urine specimens were positive, even though
      they were enrolled in drug treatment. Saliva had detectable levels of BE for only
      one child (1/17) and one adult (1/17). Forehead swabs contained measurable
      quantities of cocaine for most children (19/26) and adults (15/17) and BE for
      children (7/26) and adults (7/17). Unlike urine results, overall hair cocaine
      concentrations for adults paralleled those of children and a clear cut-off
      concentration could not be established to differentiate these two groups.

PMID- 9032953
TI  - Electrophoretic analysis of non-human primates hair keratin.
AB  - Keratin characterization through electrophoretic techniques has been used for
      species identification in forensic science and in taxonomic studies. In the
      present work, protein components solubilized from hair of non-human primates were
      evaluated to investigate whether there is any species-specific pattern in an
      evolutionary perspective, by grossly comparing hair native keratins separated by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      isoelectric focusing (IEF). Extracted hair keratins for all specimens were
      separated by SDS-PAGE into 2-3 polypeptide bands with apparent MW in the range 39
      54 kDa and into 3-7 polypeptide bands with apparent MW in the range 10-35 kDa.
      With this technique it was possible to distinguish different suborders, different
      families of the same suborder, and, sometimes, different genera from the same
      family. On the contrary, it was not possible to distinguish different species of
      the same genus and different specimens of the same species. With IEF, extracted
      hair keratins were separated into about 30 polypeptide bands with pI values in
      the range of pH 3.9-7.7. IEF discriminates poorly between different samples. Only
      in specimens from Papio genus did we find an additional polypeptide band. In
      conclusion, we found that the differences between electrophoretic patterns are
      largest for animals that are not closely related while specimens of the same
      species have the same patterns.

PMID- 9032954
TI  - Estimation of carboxyhemoglobin concentrations in thermo-coagulated blood on a CO
      oximeter system: an experimental study.
AB  - In order for forensic toxicological application of a CO-oximeter system to
      carboxyhemoglobin (CO-Hb) analysis of thermo-coagulated blood, an experimental
      study was performed. Blood samples containing varying concentrations of CO-Hb
      were gradually heated up to 70-80 degrees C in ca. 1-13 min, and the extracts
      (soluble fractions) were examined. CO-Hb contents in the extracts did not
      represent those in whole thermo-coagulated blood, showing a considerable increase
      especially for the samples with the initial CO-Hb levels of ca. 25-50%. Changes
      in CO-Hb % measurements depended little on the heating time but greatly on the
      final temperature of the blood. The apparent increase in CO-Hb measurements
      proved to be significantly related to the decrease in total soluble hemoglobin
      due to thermo-coagulation which depended on the CO-Hb contents, not due to CO-Hb
      formation by heat. Although gas chromatographic analysis of CO combined with
      appropriate measurement of total hemoglobin would be required for accurate CO-Hb
      determination of thermo-coagulated blood, a possible method for rough estimation
      (semiquantitative screening) of CO-Hb content in whole thermo-coagulated blood
      with the CO-oximeter was proposed on the basis of thermostability of CO-Hb. The
      estimated CO-Hb values correlated with the contents measured by a gas
      chromatographic method independently of the heating time or final temperature up
      to 80 degrees C.

PMID- 9032955
TI  - Immunohistochemical investigation of pulmonary surfactant in perinatal
      fatalities.
AB  - In order to verify forensic pathological significance of immunohistochemical
      investigation of pulmonary surfactant, 11 forensic and 16 clinico-pathological
      cases of perinatal death were comparatively examined. Surfactant appeared in some
      infants of 31-32 weeks gestation and was usually positive thereafter, indicating
      maturity of fetal lungs, although it may not have fully developed until about the
      36th week of gestation. It was negative in all cases of the hyaline membrane
      disease except for a full-term infant (secondary respiratory distress syndrome).
      In usual cases, surfactant coating the expanded alveolar epithelia with its
      diffuse deposit in the intra-alveolar spaces was considered to indicate duration
      of hypoxia under persistent respiration (agonal state). Such finding was most
      intensely observed in asphyxia and in severe respiratory failure from intrinsic
      causes in the infants over ca. 36 weeks of gestation. With reference to pulmonary
      micromorphology, the amount of intra-alveolar surfactant seemed to be most
      closely related to the alveolar septal (interstitial) edema.

PMID- 9032956
TI  - Portuguese population data on the six short tandem repeat loci--CSF1PO, TPOX,
      THO1, D3S1358, VWA and FGA.
AB  - Allele frequencies for six tetrameric short tandem repeat (STR) loci CSF1PO,
      TPOX, THO1, D3S1358, VWA and FGA were determined in a Caucasian population sample
      from Portugal. All loci are highly polymorphic and meet Hardy-Weinberg
      expectations. There is little evidence for association of alleles among the six
      loci. The three loci D3S1358, VWA and FGA are more polymorphic and, hence, are
      more informative than the loci CSF1PO, TPOX, and THO1. However, all six loci
      would be useful for human identification applications. The STR allelic frequency
      data are similar to other Caucasian data.

PMID- 9032957
TI  - Role of iron in the pathogenesis of Mycobacterium avium infection in mice.
AB  - Mycobacterial infections are of serious concern to HIV-infected patients, and
      take a heavy toll of such patients. Mycobacterium avium is the most common
      opportunistic bacterial infection in patients with AIDS. The overload of iron in
      serum has been implicated in the pathogenicity of a number of bacterial
      infections. Since iron storage in cells such as macrophages is increased in AIDS,
      the role of iron as a possible factor in the pathogenesis of M. avium infection
      was examined. Supplementing iron to normal laboratory chow resulted in
      accelerated M. avium infection in mice inoculated earlier with the same organism.
      The bacterial loads in liver, spleen and lungs were approximately 12-fold higher
      in mice receiving iron supplementation compared with control groups. This is
      attributed to an increased percentage saturation of iron in the sera of the mice,
      thus making more iron available for the replication of bacteria. The addition of
      beef fat to the diet, together with high iron supplementation, further enhanced
      the infection. Using smaller inocula, mice receiving chow supplemented with high
      iron and fat developed disseminated M. avium infection faster than control mice.
      The results provide strong evidence that iron may play a major role in the
      pathogenesis of M. avium infection.

PMID- 9032958
TI  - Effect of bisquaternary ammonium salts on Salmonella typhimurium.
AB  - The effect of 4,7-dioxo-3,8-dioxadekan-1, 1[bis(alkyl-dimethyldiammonium
      dibromides)] on growth, synthesis of macromolecules, respiration and induction of
      prophage in Salmonella typhimurium cells was studied. Only those compounds with
      alkyl chains of C10-C12 (octyl, decyl) in their molecules showed antimicrobial
      efficacy and inhibition incorporation of [14C]-adenine and [14C]-leucine as
      precursors of macromolecular biosynthesis. The highest inhibition of endogenous
      respiration was evoked by compounds with a long alkyl chain in the molecule
      (tetradecyl, hexadecyl). Endogenous respiration of the cells was more sensitive
      to a compound with hexadecyl than the respiration of various intermediates of the
      Krebs cycle. The sub-MICs of compounds with octyl induced a prophage of a
      lysogenic S. typhimurium strain.

PMID- 9032960
TI  - Are IgG antibody avidity assays useful in the diagnosis of infectious diseases? A
      review.
AB  - The reliability of tests for the identification of low avidity specific IgG in
      infectious diseases was investigated. The IgG antibody avidity assays were
      proposed in order to examine the probable aetiology, the accurate moment of
      primary infection and to distinguish between reactivation, reinfection or primary
      infection, in cases with false positive IgM or without specific IgM response.
      Such assays improve the usual serological techniques.

PMID- 9032959
TI  - Is the coccoid form of Helicobacter pylori viable?
AB  - Helicobacter pylori was grown on solid medium for up to 5 weeks. Morphological
      conversion from spiral to coccoid forms began after 7 days incubation under
      microaerophilic conditions. Similar to the exponential cultures, the ageing
      bacteria produced alkaline phosphatase, acid phosphatase, leucine arylamidase and
      naphthol-AS-beta 1-phosphohydrolase, although there was a reduction in the levels
      of the latter two enzymes. Unlike the other enzymes, urease was not detected in 5
      week-old cultures. By using primers based on urease subunit C and 26 kD protein
      genes for polymerase chain reaction (PCR) these two important gene fragments
      remained conserved despite the morphological conversion from spiral to coccoid
      forms. Furthermore, PCR-based random amplified polymorphic DNA (RAPD)
      fingerprinting showed similar DNA banding patterns from bacteria of various ages,
      demonstrating the conservation of the DNA composition despite morphological
      changes. This study shows that the aging coccoid form of H. pylori, although
      reportedly non-culturable in vitro, remains genetically unchanged indicating that
      it is likely to be viable.

PMID- 9032961
TI  - Phenylalanine utilization for protein synthesis in beta-phenylpyruvic acid
      treated Escherichia coli cells.
AB  - The possibility of coupling along the supply routes of phenylalanine from its
      uptake by the cell, through the charging of specific tRNAs, has been postulated.
      The experimental approach to testing this hypothesis has been to study the
      competition between endogenously synthesized and exogenously supplied amino
      acids, from which preferences for their incorporation into cellular proteins can
      be deduced. The results indicate that manipulation of the endogenous
      phenylalanine pool size, achieved by addition of its immediate precursor, beta
      phenylpyruvate, does not cause the predicted changes in the incorporation of
      exogenous labelled phenylalanine into proteins. The evidence favours exogenous
      phenylalanine being preferentially delivered to the sites of protein synthesis.

PMID- 9032962
TI  - The excessive production of indole-3-acetic acid and its significance in studies
      of the biosynthesis of this regulator of plant growth and development.
AB  - Because of the importance of indole-3-acetic acid (IAA) in the growth and
      development of plants, extensive studies of the biosynthesis of IAA have been
      performed during the four decades since the discovery of IAA as a plant hormone.
      The pathway for the biosynthesis of IAA in plants remains, however, to be
      unelucidated, even though studies within the past decade have revealed unexpected
      aspects of such biosynthesis. By contrast, two pathways to IAA have been
      characterized in bacteria at the molecular level: the indole-3-acetamide (IAM)
      pathway (L-tryptophan-->IAM-->IAA); the indole-3-pyruvic acid pathway (L
      tryptophan-->indole-3-pyruvic acid-->indole-3-acetaldehyde-->IAA) (Fig. 1). In
      both pathways, the details of the biosynthesis of IAA were clarified using IAA
      overproducing bacteria. After a description of recent advances of the studies of
      the biosynthesis of IAA in plants, this review focuses on the excessive
      production of IAA in several organisms and its significance in the studies of the
      biosynthesis of IAA.

PMID- 9032963
TI  - Novel drought-inducible genes in the highly drought-tolerant cowpea: cloning of
      cDNAs and analysis of the expression of the corresponding genes.
AB  - Ten cDNAs of genes that were induced by dehydration stress were cloned by
      differential screening from the highly drought-tolerant legume, cowpea (Vigna
      unguiculata), a major crop in West Africa. The clones were collectively named
      CPRD (cowpea clones responsive to dehydration). Northern blot analysis revealed
      that nine of the CPRD genes were induced by dehydration stress, but the timing of
      induction of mRNA synthesis varied among the CPRD genes. We analyzed the effects
      of other environmental stresses on the expression of the CPRD8, CPRD14 and CPRD22
      genes, and we found that these genes were strongly induced by high-salinity
      stress but not by cold or heat stress. Drought-stressed cowpea plants accumulated
      abscisic acid (ABA) to a level that was 160 times higher than that in unstressed
      plants. The CPRD8 and CPRD22 genes were induced to a significant extent by the
      application of exogenous ABA but the CPRD14 gene was not. These results indicate
      the existence of at least two signal-transduction pathways between the detection
      of water stress and the expression of CPRD genes in cowpea. Sequence analysis of
      CPRD8 and CPRD22 cDNAs revealed that they encoded putative proteins that were
      related to old yellow enzyme and group 2 LEA proteins, respectively. The protein
      encoded by CPRD14 exhibited sequence homology to dihydroflavonol-4-reductase
      (DFR) and vestitone reductase (VR). Old yellow enzyme, DFR and VR have not been
      identified as drought-inducible proteins in other plants, whereas LEA genes have
      been well characterized as drought-inducible genes. The various gene products
      might function to protect cells from environmental stress.

PMID- 9032964
TI  - Vacuolar function in the phosphate homeostasis of the yeast Saccharomyces
      cerevisiae.
AB  - We studied physiological roles of the yeast vacuole in the phosphate metabolism
      using 31P-in vivo nuclear magnetic resonance (NMR) spectroscopy. Under phosphate
      starvation wild-type yeast cells continued to grow for two to three generations,
      implying that wild-type cells contain large phosphate pool to sustain the growth.
      During the first four hours under the phosphate starved condition, the cytosolic
      phosphate level was maintained almost constant, while the vacuolar pool of
      phosphate decreased significantly. 31P-NMR spectroscopy on the intact cells and
      perchloric acid (PCA) extracts showed that drastic decrease of polyphosphate took
      place during this phase. In contrast, delta slp1 cells, which were defective in
      the vacuolar compartment, thus lacked polyphosphate, ceased their growth
      immediately when they faced to phosphate starvation. Taken together, we conclude
      that vacuolar polyphosphate provides an active pool for phosphate and is
      mobilized to cytosol during phosphate starvation and sustained cell growth for a
      couple rounds of cell cycle.

PMID- 9032965
TI  - Genetic analysis of the effects of polar auxin transport inhibitors on root
      growth in Arabidopsis thaliana.
AB  - Polar auxin transport inhibitors, including N-1-naphthylphthalamic acid (NPA) and
      2,3,5-triiodobenzoic acid (TIBA), have various effects on physiological and
      developmental events, such as the elongation and tropism of roots and stems, in
      higher plants. We isolated NPA-resistant mutants of Arabidopsis thaliana, with
      mutations designated pir1 and pir2, that were also resistant to TIBA. The
      mutations specifically affected the root-elongation process, and they were shown
      ultimately to be allelic to aux1 and ein2, respectively, which are known as
      mutations that affect responses to phytohormones. The mechanism of action of
      auxin transport inhibitors was investigated with these mutants, in relation to
      the effects of ethylene, auxin, and the polar transport of auxin. With respect to
      the inhibition of root elongation in A. thaliana, we demonstrated that (1) the
      background level of ethylene intensifies the effects of auxin transport
      inhibitors, (2) auxin transport inhibitors might act also via an inhibitory
      pathway that does not involve ethylene, auxin, or the polar transport of auxin,
      (3) the hypothesis that the inhibitory effect of NPA on root elongation is due to
      high-level accumulation of auxin as a result of blockage of auxin transport is
      not applicable to A. thaliana, and (4) in contrast to NPA, TIBA itself has a weak
      auxin-like inhibitory effect.

PMID- 9032966
TI  - Tissue-specific expression conferred by the S-adenosyl-L-methionine synthetase
      promoter of Arabidopsis thaliana in transgenic poplar.
AB  - In Arabidopsis the promoter of the gene encoding S-adenosyl-L-methionine
      synthetase (SAM-S) Psam-1 confers expression preferentially in the vascular
      tissue. In search for promoters that drive expression in particular cells of the
      lignifying tissues in trees, we have analyzed the expression pattern conferred by
      the Psam-1 promoter in transgenic poplar. Histochemical analyses demonstrated
      beta-glucuronidase (GUS) activity mainly in phloem and cortex tissue throughout
      the plant, and in root tips. Fluorimetric assays showed high GUS activity in the
      tissues outside (phloem, cortex and cork) compared to those inside (xylem and
      pith) of the cambial layer. In contrast, the endogenous SAM-S activity was high
      in tissues inside and low in tissues outside of the cambial layer. RNA gel blot
      analysis demonstrated a high transcript level of the endogenous sam-s gene(s) in
      tissues both outside and inside the cambial layer. This indicates that the low
      SAM-S activity in the bark was at least partially due to translational and/or
      post-translational regulation of the endogenous sam-s gene(s). In dormant
      transgenics, the tissue specificity was conserved, but the activity levels were
      up to 10-fold reduced.

PMID- 9032967
TI  - Disruption analysis of the gene for a cold-regulated RNA-binding protein, rbpA1,
      in Anabaena: cold-induced initiation of the heterocyst differentiation pathway.
AB  - A cold-regulated operon, rbpA1-rpsU, encodes an RNA-binding protein and a
      ribosomal protein in Anabaena variabilis M3. The level of expression of this gene
      cluster was about ten times higher at temperatures below 30 degrees C than at 38
      degrees C. To study the role of the RbpA1 protein in vivo, we constructed
      insertional disruptants of rbpA1. These strains were totally devoid of RbpA1
      protein but contained a normal level of the ribosomal protein S21, a product of
      the rpsU gene. The disruptants were morphologically normal at 38 degrees C, but
      at 22 degrees C they produced unusual cells at a low frequency. These cells were
      probably at an initial stage of proheterocyst formation. Various molecular events
      that are related to heterocyst initiation, namely, excision of the 11-kbp DNA
      element in nifD and the accumulation of transcripts of xisA and hetR, also
      occurred in the disruptants at 22 degrees C in the presence of nitrate ions, but
      these events did not occur in the presence of ammonium ions or at 38 degrees C.
      The results suggest that RbpA1 is required for enhanced repression of heterocyst
      initiation at low temperatures in the presence of nitrate. Possible mechanisms of
      the action of RabA1 are discussed.

PMID- 9032968
TI  - Differential expression of three genes for different beta-tubulin isotypes during
      the initial culture of Zinnia mesophyll cells that divide and differentiate into
      tracheary elements.
AB  - Complementary DNA clones for three different beta-tubulin isotypes (ZeTubB1,
      ZeTubB2 and ZeTubB3) were isolated from a cDNA library generated from RNA of
      cultured mesophyll cells of Zinnia elegans that were differentiating into
      tracheary elements and/or dividing. Sequence analysis revealed that the proteins
      encoded by ZeTubB1 and ZeTubB3 and that encoded by ZeTubB2 were each homologous
      to two of three groups of beta-tubulin isotypes in Arabidopsis. RNA gel blot
      analysis of the expression of the ZeTubB transcripts indicated that transcripts
      that corresponded to each clone were differently expressed during culture of
      Zinnia mesophyll cells. In particular, the level of expression of ZeTubB1 and
      ZeTubB3 transcripts increased rapidly prior to cell division and secondary wall
      formation, and such expression was promoted by combinations of auxin and
      cytokinin that induced tracheary element differentiation as well as cell
      division. Results of an in situ hybridization experiment with an antisense RNA
      probe derived from ZeTubB1 cDNA suggested the preferential expression of ZeTubB
      transcripts in differentiating xylem cells, as well as in the ground meristem and
      the procambium, of Zinnia seedlings.

PMID- 9032969
TI  - Identification and amino acid sequences of tryptic peptides of a novel ferredoxin
      NADP+ oxidoreductase from rice.
AB  - A 37-kDa protein purified from rice thylakoid membranes has been identified as a
      ferredoxin-NADP+ oxidoreductase based on its catalysis of the reduction of nitro
      blue tetrazolium via NADPH and its recognition by antibodies against ferredoxin
      NADP+ oxidoreductase. Amino acid sequences determined from tryptic fragments of
      the enzyme further confirm the identity of the protein and show the presence of
      unique sequences at the amino-terminus.

PMID- 9032970
TI  - Preparation of a monoclonal antibody against soybean nodule uricase (nod-35), and
      immunoblot analysis of the expression of nod-35 in tissues of various legumes.
AB  - Immunoblot analysis showed that uricases in non-ureide-transporting determinate
      nodules (Canavalia gladiata and Lotus japonicus) did not react with a monoclonal
      antibody against soybean nodule uricase, suggesting different immunological
      reactivities from those of uricases of ureide-transporting legumes.

PMID- 9032971
TI  - Identification of castasterone, 6-deoxocastasterone, typhasterol and 6
      deoxotyphasterol from the shoots of Arabidopsis thaliana.
AB  - Endogenous brassinosteroids in the shoots of Arabidopsis thaliana were
      investigated. Castasterone, 6-deoxocastasterone, typhasterol and 6
      deoxotyphasterol were identified by GC-MS. The co-occurrence of 6-deoxo
      brassinosteroids and 6-oxo-brassinosteroids suggests that there are both early
      and late C6-oxidation pathways of brassinosteroids in A. thaliana.

PMID- 9032973
TI  - Transgene rescue in the mammary gland is associated with transcription but does
      not require translation of BLG transgenes.
AB  - Many transgenes, particularly those comprising cDNA sequences fail to be
      expressed when they are introduced into transgenic mice. We have previously shown
      that this problem can be overcome in the mammary gland by co-integrating a poorly
      expressed cDNA transgene, comprising the sheep beta-lactoglobulin promoter, with
      the efficiently expressed, unmodified beta-lactoglobulin gene. In this report we
      demonstrate that the transcription of the beta-lactoglobulin gene is associated
      with this effect because co-integration with a non-transcribed beta-lactoglobulin
      gene fails to rescue expression. By contrast, co-integration with a
      translationally inactivated beta-lactoglobulin transgene does rescue the
      expression of the second gene, but without the co-production of beta
      lactoglobulin protein.

PMID- 9032972
TI  - Do transgene arrays form heterochromatin in vertebrates?

PMID- 9032974
TI  - Proline-rich-protein promoters direct LacZ expression to the granular convoluted
      tubular cells of the submandibular gland in adult transgenic mice.
AB  - The ability of two mouse PRP gene promoters to direct the expression of the
      bacterial lacZ reporter gene was tested in transgenic mice. Transgenes A1-lacZ
      and C1-lacZ consisted of 8.2 kb A1 and 7.8 kb C1 PRP promoters respectively fused
      to the lacZ coding sequence. A1 and C1 are two A-type PRP genes isolated from the
      inbred SWR mice, which show the same gene structure and similar sequence to the
      closely related MP2 and M14 PRP genes previously cloned from outbred CD-1 mice.
      We here show that both A1-lacZ and C1-lacZ transgenes have very similar
      expression patterns: (1) they expressed the lacZ gene in all 14 established
      transgenic lines under normal (non-stimulated) conditions; (2) the expression was
      restricted to the granular convoluted tubular cells of the submandibular glands;
      (3) the expression was developmentally regulated beginning at sexual maturation
      and lasting to at least 1.5 years of age; and (4) expression in some lines was
      probably influenced by sex hormones, since higher expression was found in males
      than in females. A1-lacZ and C1-lacZ are the first transgenes derived from the
      PRP/GRP (glutamine/glutamic acid-rich protein) gene superfamily to be expressed
      in the granular convoluted tubular cells (with known endocrine functions), rather
      than in the acinar cells (with mainly exocrine functions) of the submandibular
      glands.

PMID- 9032975
TI  - Enhanced selection for homologous-recombinant embryonic stem cell clones with a
      neomycin phosphotransferase gene in antisense orientation.
AB  - Gene targeting in embryonic stem cells via homologous recombination can occur at
      a very low frequency. In order to enrich the selection for homologous
      recombinants, replacement targeting vectors are now commonly used that contain
      the thymidine kinase gene placed outside of the targeted homology. The additional
      negative selection requires the presence of antiviral drugs in the culture medium
      which are known to reduce the ability of embryonic stem cells to colonize the
      germ line. We have therefore tested alternative negative selection procedures
      with replacement targeting vectors that allow the expression of either a ribozyme
      directed against the neomycin-resistance gene (neo(r)) or of an antisense neo(r)
      RNA at random integration sites. The hammerhead ribozyme was found to be
      catalytically inactive in embryonic stem cell cultures maintained in the presence
      of the selecting drug neomycin. Thus, the replacement targeting vector that
      contains ribozyme sequences did not enhance the frequency of homologous
      recombination. However, placing a promotor sequence that can enable the
      transcription of antisense neo(r) RNA outside of the targeted homology led to a
      significant enrichment of the selection for homologous recombination. This
      enrichment is similar to previously reported enrichments obtained with the
      thymidine kinase gene. The advantage, however, is that no antiviral drugs are
      needed for the selection.

PMID- 9032976
TI  - An improved method to detect beta-galactosidase activity in transgenic mice: a
      post-staining procedure on paraffin embedded tissue sections.
AB  - The Escherichia coli beta-galactosidase gene is frequently used as a reporter
      gene in transgenic studies because its activity can be easily detected at the
      cellular level. Here we report a procedure for monitoring beta-galactosidase
      activity directly in tissue sections, which involves the use of a mixture of
      ethanol and poly-ethylene-glycol as a fixative (Kryofix) and a special paraffin
      characterized by a lower fusion point of 42 degrees C. After embedding and
      cutting, the sections are stained by the chromogenic substrate 5-bromo-4-chloro-3
      indoyl-beta-D galactopyranoside (X-Gal). This procedure allows both the retention
      of a high level of beta-galactosidase activity and the preservation of good
      tissue morphology. Furthermore, it can be combined with immunohistochemical
      methods to detect other cellular components without compromising reporter gene
      detection.

PMID- 9032977
TI  - Transfer of the yeast salt tolerance gene HAL1 to Cucumis melo L. cultivars and
      in vitro evaluation of salt tolerance.
AB  - An Agrobacterium-mediated gene transfer method for production of transgenic melon
      plants has been optimized. The HAL1 gene, an halotolerance gene isolated from
      yeast, was inserted in a chimaeric construct and joined to two marker genes: a
      selectable-neomycin phosphotransferase-II (nptII)-, and a reporter-beta
      glucuronidase (gus)-. The entire construct was introduced into commercial
      cultivars of melon. Transformants were selected for their ability to grow on
      media containing kanamycin. Transformation was confirmed by GUS assays, PCR
      analysis and Southern hybridization. Transformation efficiency depended on the
      cultivar, selection scheme used and the induction of vir-genes by the addition of
      acetosyringone during the cocultivation period. The highest transformation
      frequency, 3% of the total number of explants cocultivated, was obtained with
      cotyledonary explants of cv. 'Pharo'. Although at a lower frequency (1.3%), we
      have also succeeded in the transformation of leaf explants. A loss of genetic
      material was detected in some plants, and results are in accordance with the
      directional model of T-DNA transfer. In vitro cultured shoots from transgenic
      populations carrying the HAL1 gene were evaluated for salt tolerance on shoot
      growth medium containing 10 gl-1 NaCl. Although root and vegetative growth were
      reduced, transgenic HAL1-positive plants consistently showed a higher level of
      tolerance than control HAL1-negative plants.

PMID- 9032978
TI  - Secretion of unprocessed human surfactant protein B in milk of transgenic mice.
AB  - Because of the apparent clinical importance of human pulmonary surfactant B (SP
      B), the expression of SP-B was directed to the mammary gland of transgenic mice
      using previously characterized rat whey acidic protein (WAP) regulatory
      sequences. rWAP/SP-B mRNA was expressed specifically in the mammary gland, and
      ranged from 1 to 5% of the endogenous WAP mRNA levels. SP-B was detected
      immunologically in both tissue and milk. The transgene product had an apparent
      molecular weight of 40-45 kDa, corresponding to the predicted size of the SP-B
      proprotein. Incubation of an SP-B-enriched fraction of milk with cathepsin D in
      vitro produced 20-25 kDa species, consistent with cleavage of the amino terminal
      domain by cathepsin D. This was confirmed using antibodies specific to the
      carboxy-terminal domain of SP-B. However, the appearance of only the SP-B
      proprotein in milk suggests that cathepsin D is not involved in the in vivo
      processing of SP-B. The SP-B proprotein in milk suggests that cathepsin D is not
      involved in the in vivo processing of SP-B. The SP-B proprotein can be expressed
      in milk of transgenic mice without any observed effects on mammary gland
      morphology or lactation.

PMID- 9032979
TI  - Expression of caprine beta-lactoglobulin in the milk of transgenic mice.
AB  - A 14.5 kb-long transgene containing the complete caprine beta-lactoglobulin gene
      transcription unit as well as 6.1 kb and 3.7 kb of the 5'- and 3'-flanking
      regions, respectively, was microinjected into pronuclear stage mouse embryos.
      Four lines of transgenic mice were obtained, three of them expressing the
      transgene in their mammary glands during lactation. Western blot analysis of
      caprine beta-lactoglobulin in the milk of hemizygous transgenic animals
      demonstrated the presence of the exogenous protein at concentrations up to 0.5 mg
      ml-1 of mouse milk.

PMID- 9032980
TI  - Bovine alpha s1-casein gene sequences direct high level expression of human
      granulocyte-macrophage colony-stimulating factor in the milk of transgenic mice.
AB  - The generation is reported of transgenic mice expressing human granulocyte
      macrophage colony-stimulating factor (GM-CSF) or human erythropoietin (EPO) under
      the control of bovine alpha s1-casein regulatory sequences. GM-CSF expression was
      specific to the mammary gland, and levels of human GM-CSF in transgenic mouse
      milk were in the range of mg ml-1. The specific activity of the milk GM-CSF was
      similar to that of the recombinant protein produced in Escherichia coli, and the
      glycosylation-derived size heterogeneity corresponded to that of the native human
      protein. In spite of the identical bovine regulatory sequences of the fusion
      genes, the levels of human EPO in transgenic mouse milk were 10(3)-10(6) times
      lower than those of GM-CSF, ranging from 0.003 to 3 micrograms ml-1. There
      appeared to be a positive correlation between the amount of EPO in the milk of
      lactating females and blood haematocrit values. In view of this, other type of
      constructs should be used to achieve more efficient EPO expression and to
      circumvent concomitantly-occurring adverse effects. In contrast, the high-level
      production of recombinant GM-CSF, its resemblance to the native mammalian
      protein, and mild adverse consequences of transgene expression imply that the
      current construct could be used for generation of larger GM-CSF transgenic
      animals to produce this protein in quantities sufficient for therapeutic
      purposes.

PMID- 9032981
TI  - Sperm as a carrier to introduce an exogenous DNA fragment into the oocyte of
      Japanese abalone (Haliotis divorsicolor suportexta).
AB  - We investigated gene transfer in abalone via electroporated sperm. The mobility
      of sperm electroporated either in seawater or in marine invertebrate
      physiological solution was as good as that of the control group. The
      fertilization rate reached as high as 94.7-99.6% (93.0-99.7% for the control
      group) when 200 eggs were fertilized by 10(6) or 10(7) sperm treated with
      electroporation at 10 kV and 2(7) pulses for six cycles. Moreover, the
      fertilization rate of sperm electroporated in the presence of foreign DNA (opAFP
      2000CAT) ranging from 0.1 to 3.2 micrograms and at voltages ranging from 2 to 10
      kV, at 2(7) or 2(11) pulses for six or 12 cycles showed no differences from the
      control sperm. After DNase digestion, the genome of the electroporated sperm was
      analysed by polymerase chain reaction, and it was shown that a 138-bp product was
      amplified, corresponding to the transgene's amplification product. Southern
      blotting also showed that a positive band located at the same position as that of
      opAFP-2000CAT was found in the electroporated sperm after DNase treatment.
      Analysis by PCR of the genome isolated from a trochophore-stage abalone larva,
      derived from sperm electroporated with 3.2 micrograms opAFP-2000CAT, showed the
      existence of foreign DNA in 13 out of 20 examined samples (65%). The integration
      of the transferred DNA into the genome of transgenic abalone was also shown by
      Southern blot analysis. Furthermore, CAT activity was positive for the
      experimental larvae, but the level of CAT expression was lower than that of
      larvae derived from sperm electroporated with pCAT-Control vector, driven by SV40
      promoter and enhancer sequences. These results demonstrate the potential for the
      use of sperm as mass gene transfer strategy in marine mollusks such as abalone.

PMID- 9032983
TI  - Separation of hybridoma cells from their IgG product using aqueous two-phase
      systems.
AB  - The partitioning of IgG in aqueous two-phase systems (ATPSs) of PEG and Dextran
      was studied systematically using a statistical experimental design. Aim was to
      improve the separation of hybridoma cells and their IgG product, by identifying
      the key variables governing IgG partitioning, and by comparing the IgG
      partitioning data with the hybridoma cell partitioning data obtained in previous
      work. The influence of five factors, i.e. the poly(ethylene glycol) molecular
      weight (PEG Mw), dextran molecular weight (Dx Mw), tie-line length (TLL), pH and
      potassium phosphate fraction (KPi/(KPi+KCl)), on IgG partitioning was
      characterized using a full-factorial experimental design. In all of the ATPS's
      the IgG partitioned predominantly into the lower phase. The partition coefficient
      varied between 0.78 (Variable settings: PEG Mw = 6000, Dx Mw = 500000, TLL = 0.10
      g g-1, KPi/(KPi+KCl) = 1.0 and pH = 7.4) and 0.0002 (Variable settings: PEG Mw =
      35000, Dx Mw = 40000, TLL = 0.20 g g-1 KPi/(KPi+KCl) = 1.0 and pH 6.6). The tie
      line length, the dextran molecular weight and the PEG molecular weight had the
      most pronounced effect on IgG partitioning. Matching the partitioning data of the
      IgG product with previously obtained data of the hybridoma cell partitioning,
      showed that within the experimental design no ATPS could be found giving a good
      separation of the hybridoma cells and their IgG product. There are, however,
      ATPS's available in which the cells partition to, and grow in the lower dextran
      rich phase. To achieve a good separation of the hybridoma cells and their IgG
      product in these ATPSs, the IgG product has to be specifically extracted into the
      PEG-rich top phase. For this purpose the use affinity ligands coupled to PEG may
      offer a solution. Therefore, a number of commercially available dye-resins was
      screened for their ability to bind the BIF6A7 IgG antibody. The mimetic green 1
      A6XL dye-resin was found to bind BIF6A7 IgG. The dye-ligand coupled to PEG was
      used to manipulate the IgG partitioning in an ATPS. In the presence of the PEG
      ligand, the IgG partitioned almost completely to the top phase. The IgG-partition
      coefficient increased three orders of magnitude, resulting in a 25-fold higher
      IgG concentration in the top phase than in the bottom phase.

PMID- 9032984
TI  - Strategies for the isolation and purification of retroviral vectors for gene
      therapy.
AB  - Viral gene therapy vectors promise new opportunities for treatment of hitherto
      debilitating and life threatening illnesses. To enable early and rapid clinical
      evaluation of the therapeutic potential of the technology, the initial objectives
      of process development have so far largely concerned vector assembly, product
      quality and safety, and manufacturing consistency appropriate to modest scales.
      The first of such vectors are under test in clinical trials approved through the
      regulatory CTX/IND route and thus conform to the standards specified for purity
      and contaminant removal. Process optimisation, scale-up and operability have been
      of secondary concern and the establishment of a scientific basis for the
      mechanistic development of future vector manufacturing processes has yet to be
      seriously addressed. This review considers the manufacturing demands of
      retroviral vectors and the candidate separation technologies which could
      facilitate preparation of clinical grade materials. Note is made that the
      practising community appears to place implicit confidence in the capability of
      conventional membranes and chromatographic supports developed for protein
      purification to perform adequately for large-scale purification of viruses. In
      particular, these are expected to deliver virus preparations to product standards
      currently required of therapeutic proteins. It is argued that the basis for this
      confidence may be ill-placed, since the physical and chemical characteristics of
      viral particles differ significantly from macromolecular proteins. The specific
      requirements for separation systems and materials for processing of retroviral
      vectors are considered, and specific routes to more efficient manufacturing
      processes are proposed.

PMID- 9032982
TI  - A molecular strategy designed for the rapid screening of gene traps based on
      sequence identity and gene expression pattern in adult mice.
AB  - We have devised a strategy to rapidly screen gene traps in mouse embryonic stem
      (ES) cells based on DNA sequence information and an in vitro analysis of gene
      expression. After the initial identification of ES cell clones expressing beta
      galactosidase, tagged RNA transcripts were immediately cloned and sequenced in
      order to determine their identities. Novel gene sequences found were used to
      probe northern blots to examine the expression patterns of their cognate genes.
      Our initial characterization of 30 cDNA clones indicated that more than half of
      the tagged sequences were novel mouse genes and of these 40% showed a restricted
      pattern of expression in adult mouse tissues. This molecular characterization of
      gene traps is quick, reliable and well suited for the large-scale screening of
      mammalian developmental genes. Furthermore, since gene trap insertion frequently
      disrupts the tagged host gene, the ES cells can be used to produce transgenic
      animals for a genetic analysis of gene function.

PMID- 9032985
TI  - Improved purification of ribulose 5-phosphate 3-epimerase from Saccharomyces
      cerevisiae and characterization of the enzyme.
AB  - D-Ribulose 5-phosphate 3-epimerase from Saccharomyces cerevisiae was purified to
      homogeneity by 1970-fold enrichment elaborating the following steps: disruption
      of fresh cells, polyethylene glycol precipitation, ion exchange chromatography,
      heat-treatment, size exclusion chromatography on Sephadex G-75 and Bio-Sil SEC
      125 and hydrophobic interaction chromatography. A molecular mass of 50 +/- 4 kDa
      was determined for the native enzyme by sedimentation equilibrium experiments.
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a single band
      with 26 kDa which has been characterized as an individual polypeptide chain.
      Thus, the enzyme is a dimer composed of two identical subunits. The specific
      activity of the purified enzyme with 7700 units/mg protein was found to be 30
      fold higher than described in previous papers. The enzyme shows a hyperbolic
      dependence of the catalytic activity towards ribulose 5-phosphate with a KM-value
      of 1.5 mmol/l. The N-terminal amino acid sequence analysis of the native enzyme
      and of several peptides obtained by chemical and proteolytic fragmentation
      provided a part of the primary structure which fits to the primary structure
      deduced from the DNA sequence.

PMID- 9032986
TI  - A drug screening program for ion channels expressed in yeast.

PMID- 9032987
TI  - Making cells work--metabolic engineering for everyone.

PMID- 9032988
TI  - Environmental stress response in plants: the role of mitogen-activated protein
      kinases.
AB  - Mitogen-activated protein kinase (MAPK) cascades have essential roles in diverse
      intracellular signaling processes in plants, animals and yeasts. In plants,
      transcription of genes encoding protein kinases involved in MAPK cascades is
      upregulated by environmental stresses and plant hormones; in addition, MAPK-like
      kinase activities are transiently activated in response to environmental
      stresses. Consequently, MAPK cascades are now thought to have important roles in
      stress signal transduction pathways in higher plants.

PMID- 9032989
TI  - Bacterial and archaeal S-layer proteins: structure-function relationships and
      their biotechnological applications.
AB  - Crystalline cell surface layers (S-layers) composed of planar assemblies of
      protein or glycoprotein subunits are one of the most commonly observed cell
      envelope structures of bacteria and archaea. Isolated S-layer subunits of
      numerous organisms are able to assemble into monomolecular arrays either in
      suspension, at liquid-surface interfaces, including lipid films, on liposomes and
      on solid supports. Pores in S-layers are of regular size and morphology, and
      functional groups on the protein lattices are aligned in well-defined positions
      and orientations. These characteristic features of S-layers have led to various
      applications in biotechnology, vaccine development, diagnostics, biomimetics and
      molecular nanotechnology.

PMID- 9032990
TI  - Effect of glycosylation on antibody function: implications for genetic
      engineering.
AB  - Antibodies are able to both bind antigens and trigger the responses that
      eliminate them from circulation. All antibodies are glycosylated at conserved
      positions in their constant regions, and the presence of carbohydrate can be
      critical for antigen clearance functions such as complement activation. The
      structure of the attached carbohydrate can also affect antibody activity.
      Antibody glycosylation can be influenced by the cell in which it is produced, the
      conformation of the antibody and cell culture conditions. These variables should
      be considered in the design and production of antibodies with selected
      specificity and function.

PMID- 9032991
TI  - A 964 bp repetitive DNA in Entamoeba histolytica is associated with linear
      "chromosomal" DNAs of variable sizes.

PMID- 9032992
TI  - Identification of putative linear and circular DNA molecules in the Entamoeba
      histolytica molecular karyotype.

PMID- 9032993
TI  - Organization of Entamoeba histolytica ribosomal and structural genes in PFGE.

PMID- 9032994
TI  - In situ location of the Ehredox and 16S rDNA genes in Entamoeba histolytica
      trophozoites.

PMID- 9032995
TI  - Molecular cloning of histone H1 in Entamoeba histolytica and histone H2B in
      Entamoeba histolytica and Entamoeba dispar.

PMID- 9032996
TI  - Detection of a human p53-like protein in E. histolytica.

PMID- 9032997
TI  - The sequence of a highly homologous gene to hgl2* of Entamoeba histolytica that
      is present and expressed in E.dispar.

PMID- 9032998
TI  - Localization of a retinoblastoma-like protein in Entamoeba histolytica.

PMID- 9032999
TI  - A model for unscheduled DNA replication in Entamoeba histolytica trophozoites.

PMID- 9033001
TI  - Possible role of transcribed intergenic sequences in Entamoeba histolytica.

PMID- 9033002
TI  - Inducible gene expression in Entamoeba histolytica mediated by a tetracycline
      responsive prokaryotic repressor.

PMID- 9033000
TI  - Phenotype variability and genetic polymorphism in Entamoeba histolytica clonal
      populations.

PMID- 9033004
TI  - Upstream regions of rp L21 genes play a role in regulation of expression at the
      post-transcriptional level in E. histolytica and E. dispar.

PMID- 9033003
TI  - Establishment of an inducible expression system in Entamoeba histolytica.

PMID- 9033005
TI  - Control of gene expression in Entamoeba histolytica by a cis-acting upstream
      regulatory element.

PMID- 9033006
TI  - Three conserved cis-acting sequences in the core promoter control gene expression
      in the protozoan parasite Entamoeba histolytica.

PMID- 9033007
TI  - Comparison of the Entamoeba histolytica TATA-binding protein (TBP) structure with
      other TBP.

PMID- 9033008
TI  - Structural characterization of the Entamoeba histolytica enolase gene promoter.

PMID- 9033009
TI  - Stable transfection of Entamoeba histolytica trophozoites by lipofection.

PMID- 9033010
TI  - Transfection of Entamoeba dispar: inhibition of expression of the lysine-rich 30
      kDa surface antigen by the transcription of its antisense RNA.

PMID- 9033011
TI  - The secretory pathway of Entamoeba histolytica: characterization and expression
      of the SRP54 gene.

PMID- 9033012
TI  - The secretory pathway of Entamoeba histolytica: characterization and expression
      of the ERD2 gene.

PMID- 9033013
TI  - Characterization of the 5'-flanking region of the EhPgp1 gene of multidrug
      resistance in Entamoeba histolytica.

PMID- 9033014
TI  - Characterization of 5'-flanking sequence of the EhPgp5 gene of multidrug
      resistance in Entamoeba histolytica.

PMID- 9033015
TI  - Putative amplification of the EhPgp genes in Entamoeba histolytica emetine
      resistant mutants.

PMID- 9033016
TI  - Molecular phylogeny of the genus Entamoeba as revealed by riboprinting.

PMID- 9033017
TI  - A revised endosymbiont hypothesis to explain the bacterial origin of amebic
      glycolytic and fermentation enzymes.

PMID- 9033018
TI  - Isolation and purification of glutathionyl-spermidine and trypanothione from
      Entamoeba histolytica.

PMID- 9033019
TI  - Cloning and expression of E. histolytica gene which includes a putative PDI
      active site.

PMID- 9033020
TI  - Expression of the alcohol dehydrogenase (ADH) domain of Entamoeba histolytica
      EhADH2 enzyme.

PMID- 9033021
TI  - Molecular cloning and biochemical characterization of hexokinases and
      phosphoglucomutases from Entamoeba histolytica and Entamoeba dispar.

PMID- 9033022
TI  - Two genes for PPi-dependent phosphofructokinase in Entamoeba histolytica.

PMID- 9033023
TI  - Molecular modeling of phosphofructokinase from Entamoeba histolytica for the
      prediction of new antiparasitic agents.

PMID- 9033024
TI  - Subcellular location of the pyruvate: ferredoxin oxidoreductase from Entamoeba
      histolytica.

PMID- 9033025
TI  - Characterization of two E. histolytica proteins that inactivate reactive oxygen
      species.

PMID- 9033026
TI  - The detoxicating enzymes of Entamoeba histolytica and their detoxifying roles.

PMID- 9033027
TI  - Identification of three Entamoeba histolytica intracellular acyl-hydrolase
      activities.

PMID- 9033028
TI  - Cholesterol requirement and metabolism in Entamoeba histolytica.

PMID- 9033029
TI  - The lipophosphoglycan-like molecules of virulent and avirulent E. histolytica as
      well as of E. dispar differ in both composition and abundance.

PMID- 9033030
TI  - Preservation of cysteine proteinases and other Entamoeba histolytica proteins
      from autoproteolysis.

PMID- 9033031
TI  - Long-term subcultivation in axenic conditions of Entamoeba histolytica in a serum
      free media.

PMID- 9033032
TI  - Entamoeba dispar: cultivation without viable associate and its characterization.

PMID- 9033033
TI  - Zinc: interference with the calcium function in Entamoeba histolytica.

PMID- 9033034
TI  - Comparative ultrastructural studies of the cell surface and endocytic vacuoles of
      Entamoeba histolytica Schaudinn, 1903 and Entamoeba dispar Brumpt, 1925.

PMID- 9033035
TI  - Entamoeba dispar: ultrastructure and cytopathic effect.

PMID- 9033036
TI  - A comparison in the ultrastructure of nuclear and extra-nuclear DNA of Entamoeba
      histolytica.

PMID- 9033037
TI  - Characterization of cell division cycle regulating genes of Entamoeba histolytica
      by flow cytometry.

PMID- 9033038
TI  - A morphodynamic study of the structural organization of Entamoeba histolytica
      chromatin during nuclear division.

PMID- 9033039
TI  - Signal transduction mechanisms in Entamoeba histolytica trophozoites.

PMID- 9033040
TI  - Rac G, a small GTPase, regulates capping of surface receptors in Entamoeba
      histolytica.

PMID- 9033041
TI  - Partial characterization of G proteins and PLC as possible signal transduction
      elements during adhesion of Entamoeba histolytica to fibronectin.

PMID- 9033042
TI  - cAMP levels and up-regulation of actin mRNA in Entamoeba histolytica.

PMID- 9033043
TI  - Molecular cloning of an Entamoeba histolytica gene encoding a polypeptide with
      similarities to actin-binding proteins.

PMID- 9033044
TI  - The tail domain of Entamoeba histolytica myosin IB bind F-actin.

PMID- 9033045
TI  - Proteasome function is required for encystation of Entamoeba invadens.

PMID- 9033046
TI  - Stimulation of Entamoeba histolytica cyst wall polysaccharide synthesis by three
      divalent cations.

PMID- 9033047
TI  - Cyst-specific exochitinases of Entamoebae contain unique hydrophilic repeats at
      their amino termini.

PMID- 9033048
TI  - Development of monoclonal antibodies directed against cysts of Entamoeba
      histolytica and Entamoeba dispar.

PMID- 9033049
TI  - Entamoeba invadens differentiation and Entamoeba histolytica cyst-like formation
      induced by CO2.

PMID- 9033050
TI  - Molecular basis of aggressive and defensive functions of Entamoeba histolytica.

PMID- 9033051
TI  - Oxygen free radicals produced by Entamoeba histolytica are able to cause
      biological damage.

PMID- 9033052
TI  - Potency of amoebapores compared to that of other membrane-permeating peptides.

PMID- 9033053
TI  - Calcium-independent cytolysis of target cells induced by Entamoeba histolytica.

PMID- 9033054
TI  - Adhesive and chemotactic properties of fibronectin and fibronectin-derived
      fragments on Entamoeba histolytica trophozoites.

PMID- 9033055
TI  - Identification and location of the cell-binding domain in the 112 kDa adhesin
      gene of Entamoeba histolytica.

PMID- 9033056
TI  - Involvement of the 112 kDa adhesin in Entamoeba histolytica phagocytosis.

PMID- 9033057
TI  - Structure and function of the galactose/N-acetyl D-galactosamine inhibitable
      adhesin of Entamoeba dispar.

PMID- 9033058
TI  - Transfer of the Gal/GalNAc-specific amebic lectin from trophozoites to frozen
      sections of human colon mucosa.

PMID- 9033059
TI  - Entamoeba histolytica: partial cloning and expression of cDNAs encoding a 30 kDa
      collagen-binding protein.

PMID- 9033060
TI  - Entamoeba histolytica: role of surface proteases on its virulence.

PMID- 9033061
TI  - Cleavage of IgG by the neutral cysteine proteinase of E. histolytica.

PMID- 9033062
TI  - A novel cysteine protease in Entamoeba histolytica.

PMID- 9033063
TI  - Membrane acid phosphatase (MAP) from Entamoeba histolytica.

PMID- 9033064
TI  - Secreted Entamoeba histolytica acid phosphatase (SAP).

PMID- 9033065
TI  - A 148-kDa secretory proteinase from Entamoeba histolytica.

PMID- 9033066
TI  - Electron dense granules and the pathogenicity in Entamoeba histolytica.

PMID- 9033067
TI  - Differential display of mRNAs from Entamoeba histolytica during electron dense
      granules secretion.

PMID- 9033068
TI  - The cytoskeleton in Entamoeba histolytica during EDG secretion.

PMID- 9033069
TI  - Selective interaction of Entamoeba histolytica with lactobacilli and other
      intestinal bacteria.

PMID- 9033070
TI  - Erythrophagocytosis by Entamoeba histolytica.

PMID- 9033071
TI  - Entamoeba histolytica: kinetics of hemolytic activity, erythrophagocytosis and
      digestion of erythrocytes.

PMID- 9033072
TI  - Hemoglobinases in Entamoeba histolytica HM-1: IMSS.

PMID- 9033073
TI  - In vivo pathogenesis of Entamoeba dispar.

PMID- 9033074
TI  - Morphological analysis of amebic liver abscess produced by intraperitoneal
      inoculation of Entamoeba histolytica trophozoites in hamsters.

PMID- 9033075
TI  - Early in vivo interaction of Entamoeba histolytica trophozoites with hepatic
      parenchymal and inflammatory cells of hamster.

PMID- 9033076
TI  - Role of nitric oxide in experimental hepatic amebiasis.

PMID- 9033077
TI  - Metabolism of arachidonic acid during amebic abscess formation in hamster.

PMID- 9033078
TI  - Production of amebic intestinal lesions in BALB/c mice.

PMID- 9033079
TI  - Secreted Entamoeba histolytica proteins stimulate interleukin-8 mRNA expression
      and protein production in human colonic epithelial cells.

PMID- 9033080
TI  - Cholera toxin increases rat serum and mucosal antibody responses against
      Entamoeba histolytica trophozoites.

PMID- 9033081
TI  - The galactose adherence lectin of Entamoeba histolytica activates primed
      macrophages for amebicidal activity mediated by nitric oxide.

PMID- 9033082
TI  - Role of the neutrophil in the pathogenesis of the amebic liver lesion in mice.

PMID- 9033083
TI  - The monocyte locomotion inhibitory factor (MLIF) produced by axenically grown
      Entamoeba histolytica fails to affect the locomotion and the respiratory burst of
      human eosinophils in vitro.

PMID- 9033084
TI  - Production of the monocyte locomotion inhibitory factor (MLIF) by axenically
      grown Entamoeba histolytica: synthesis or degradation?

PMID- 9033085
TI  - Inhibition of contact cutaneous delayed hypersensitivity reactions to DNBC in
      guinea pigs by the monocyte locomotion inhibitory factor (MLIF) produced by
      axenically grown Entamoeba histolytica.

PMID- 9033086
TI  - Cross reactivity of mouse monoclonal antibodies to glycoprotein with two
      different antigens from the outer membrane of Entamoeba histolytica.

PMID- 9033087
TI  - Identification of an idiotype on mouse monoclonal antibody directed to a 35 kDa
      glycoprotein from Entamoeba histolytica.

PMID- 9033088
TI  - Increased frequency of HLA-DR3 and complotype SC01 in Mexican Mestizo children
      with amebic abscess of the liver and summary of our overall HLA-SC01 experience
      in invasive amebiasis.

PMID- 9033089
TI  - Frequency of HLA in adult E.histolytica/E.dispar cyst passer population.

PMID- 9033090
TI  - Serum cytokines of acute phase response in the amebic liver abscess.

PMID- 9033091
TI  - Rapid isolation of lymphocytes of the large and small intestine to assess anti
      Entamoeba histolytica immune response.

PMID- 9033092
TI  - Inhibition of proteolytic activity of Entamoeba histolytica by human colostrum
      IgA antibodies.

PMID- 9033093
TI  - A new isoform of the serine-rich E. histolytica protein recognized by human
      secretory IgA antibodies from patients with intestinal amebiasis.

PMID- 9033095
TI  - Identification of A 35 kDa glycoprotein from the outer membrane of Entamoeba
      histolytica by sera from patients with amebic liver abscess and with mouse
      monoclonal antibody.

PMID- 9033096
TI  - Preliminary study of the 220 kDa lectin-elicited immune response in hamster:
      possible vaccine candidate.

PMID- 9033094
TI  - Entamoeba histolytica 60 kDa cysteine proteinase and its relationship with the
      humoral immune response.

PMID- 9033097
TI  - Progress in an oral vaccine for amebiasis. Expression of the serine rich
      Entamoeba histolytica protein (SREHP) in the avirulent vaccine strain Salmonella
      typhi TY2 chi 4297 (delta cya delta crp delta asd): safety and immunogenicity in
      mice.

PMID- 9033098
TI  - Variants of amebic liver abscess.

PMID- 9033099
TI  - A proposal for a molecular biologic system for classifying isolates of Entamoeba
      histolytica and Entamoeba dispar.

PMID- 9033100
TI  - Evaluation of an enzyme-immunoassay test kit for diagnosing infections with
      Entamoeba histolytica.

PMID- 9033101
TI  - Detection and differentiation of Entamoeba histolytica and E. dispar using an
      improved colorimetric polymerase chain reaction method.

PMID- 9033102
TI  - Diagnosis of Entamoeba histolytica and Entamoeba dispar in clinical specimens by
      PCR-SHELA.

PMID- 9033104
TI  - Entamoeba histolytica: axenization and characterization of isolated samples from
      symptomatic and asymptomatic patients from different regions of Brazil.

PMID- 9033103
TI  - Characterization of two venezuelian Entamoeba histolytica strains using
      electrophoretic isoenzyme patterns and PCR-SHELA.

PMID- 9033105
TI  - Patterns of the morbidity and mortality of amebiasis and amebic liver abscess in
      Mexico: an ecological analysis.

PMID- 9033106
TI  - Cost-effectiveness analysis of treatment of E. histolytica/E. dispar cyst
      carriers.

PMID- 9033107
TI  - In vitro susceptibility of Entamoeba histolytica to fluoroquinolones, nitrofurans
      and other antiamebic agents.

PMID- 9033109
TI  - Determination of the antiamebic effect of a metronidazole/gossypol blend.

PMID- 9033108
TI  - Gossypol anti-amebic effect in vivo.

PMID- 9033110
TI  - A morphodynamic live study of the interaction of metronidazole with E.
      histolytica trophozoites using acridine orange.

PMID- 9033111
TI  - Zymodeme stability of Entamoeba histolytica and E. dispar.

PMID- 9033113
TI  - Epidemiological study of amebiasis in Chihuahua, Mexico.

PMID- 9033112
TI  - Detection of anti-Entamoeba histolytica IgA salivary antibodies: evaluation of
      its diagnostic capability in a rural setting.

PMID- 9033114
TI  - High rate of occult infection with Entamoeba histolytica among non-dysenteric
      Mexican children.

PMID- 9033115
TI  - Amebiasis in Leon, Nicaragua: Entamoebae in stool examination and identification
      of amebic liver abscess cases by serology and PCR.

PMID- 9033116
TI  - Entamoeba histolytica and Entamoeba dispar infection in children in Bangladesh.

PMID- 9033117
TI  - An epidemiological study of Entamoeba histolytica and E. dispar infection in
      eastern Turkey using a colorimetric polymerase chain reaction.

PMID- 9033118
TI  - Serologic characterization of Entamoeba histolytica asymptomatic carriers from a
      community of Puebla state, Mexico.

PMID- 9033119
TI  - Humoral immune response to E. histolytica/E. dispar during the first year of
      life. A cohort study.

PMID- 9033121
TI  - Leszek Janiszewski (1925-1996).

PMID- 9033120
TI  - Anti-E. histolytica IgA antibodies in saliva of E. histolytica or E.dispar
      infected individuals: longitudinal study of cohorts.

PMID- 9033122
TI  - Cholinergic modulation of synaptic transmission in horizontal connections of rat
      motor cortex.
AB  - The influence of compounds interacting with cholinergic systems on field
      potentials evoked in layer II/III horizontal connections was investigated in rat
      motor cortex in vitro. The cholinesterase inhibitor eserine (10 microM) decreased
      field responses by 20 +/- 2%. This effect could be prevented by preincubation
      with atropine (10 microM). Application of 5 microM carbachol resulted in
      reduction of the responses by 30 +/- 1%. These reductions were reversible,
      repeatable and independent of stimulus intensity; they could be blocked by the M1
      muscarinic receptor antagonist pirenzepine (3 microM) but not by the M2
      muscarinic receptor antagonist gallamine (10 microM). During carbachol
      application, paired-pulse facilitation (40 ms interpulse interval) was increased.
      The results indicate that endogenous acetylcholine may modulate excitatory
      synaptic transmission in horizontal connections of rat motor cortex, most likely
      by acting upon M1 receptors located presynaptically on glutamatergic terminals,
      and may contribute both to information processing and synaptic plasticity within
      the motor cortex.

PMID- 9033123
TI  - Spatial organization of receptive fields of cat's. Hippocampal visually driven
      neurones.
AB  - According to the spatial configurations of receptive fields two broad groups of
      neurones in dorsal hippocampal region (HR) were distinguished. The receptive
      field borders of 22 cells have regular (R) smooth contours (squares or
      rectangles), usually with a horizontally oriented longitudinal axis. The second
      group was composed of neurones (20 cells) with irregular (IR) configurations of
      receptive fields. Some neurones (16 cells) of this group had relatively simple
      spatial configurations of receptive fields and 4 neurones had receptive fields
      with more intricate spatial configurations which formed complex geometrical
      shapes in the visual field. The exploration of the distribution of response
      properties a to stationary flashing spot over the RF surface revealed that the
      majority of cells with regular receptive fields have heterogeneous stationary
      structure with ON, ON-OFF and OFF subregions sequentially located in the
      receptive field, and these neurones, as a rule, were direction-sensitive. The
      neurones with irregular receptive fields, on the other hand, had a rather
      homogeneous structure of RFs when tested by a stationary flashing spot and only
      four neurones of 20 investigated were directionally sensitive.

PMID- 9033124
TI  - Respiratory effects of serotonin challenge to pulmonary and laryngeal circulation
      in anaesthetized cats.
AB  - Administration of serotonin (5-HT) to pulmonary circulation elicits prompt
      apnoea, followed by subsequent tachypnoea. The present study was designed to
      ascertain whether 5-HT challenge into the laryngeal artery will evoke the full
      constellation of this chemoreflex and to examine the role of laryngeal sensory
      input and importance of vagal afferents in the respiratory sequelae. The
      experiments were done on 10 anaesthetized, spontaneously breathing cats.
      Laryngeal artery injections of 5-HT, similarly to intravenous challenge, caused
      apnoeas, which were significantly diminished by the section of cervical vagal
      trunks. Breathing frequency increased in all conditions on intravenous injection
      but only prior to vagotomy, when administered into laryngeal artery. With resumed
      breathing, the peak inspiratory airflows were significantly increased in the
      neurally intact, those treated by bilateral section of the superior laryngeal
      nerves (SLNs-cut) and vagotomized cats, with no difference between them and
      independent of the route of injection. The results show that serotonin
      chemoreflex could evolve from the laryngeal vascular bed and that laryngeal
      afferents do not contribute to the respiratory arrest.

PMID- 9033125
TI  - Antagonism of the discriminative stimulus properties of cocaine with the
      combination of a dopamine D1 and D2 antagonist.
AB  - Antagonism of the discriminative stimulus properties of 10 mg/kg cocaine was
      studied in rats by use of the dopamine D1 antagonist SCH 23390 and the D2
      antagonist haloperidol. Whereas SCH 23390 and haloperidol were by themselves
      unable to antagonize the cueing properties of cocaine, the combination of both
      dopamine antagonists resulted in a complete blockade of the cocaine cue. In the
      presence of a fixed dose of 0.01 and 0.04 mg/kg haloperidol, the ED50's (it is
      the effective dose in 50% of the animals) of SCH 23390 for cocaine antagonism
      were 0.043 and 0.012 mg/kg, respectively. Similarly, the ED50's of haloperidol in
      combination with 0.01 and 0.04 mg/kg SCH 23390 were 0.021 and 0.024 mg/kg. The
      combined treatment of haloperidol and SCH 23390 resulted in strong response-rate
      reductions. At all combination regimens resulting in a complete blockade of the
      cocaine cue, response rate was reduced to less than 20% of the control values.
      These results indicate that the cueing properties of cocaine are both dopamine D1
      and D2-mediated and that a combined antagonism of both receptor subtypes can
      lead to a complete antagonism of the cueing properties of cocaine which is
      associated with severe attenuation of response rate.

PMID- 9033126
TI  - Various strategies of forelimb movement during contact placing reactions elicited
      by tactile stimulation of the different aspects of a cat's paw.
AB  - Forelimb trajectory and the activity of eight muscles operating at the elbow,
      wrist and digit joints were analyzed during contact placing (CP) reactions
      elicited by tactile stimuli applied to the lateral (L) or medial (M) side of the
      cat's forepaw to verify whether a common movement strategy was used in these
      reactions. A tactile stimulus applied to the lateral side of the paw led, most
      frequently, to a short-latency activation of the elbow flexor muscles and flexor
      carpi radialis. Stimulation of the medial side of the paw produced either a short
      latency activation of the elbow flexors or both the elbow flexor and extensor
      muscles. At the distal joints it most frequently activated extensor carpi ulnaris
      and flexor carpi radialis muscles. Different patterns of activation of the
      muscles during LCP and MCP reactions led to a diverse involvement of elbow
      flexion and extension movements at the beginning of the reactions. LCP was
      usually initiated by the elbow flexion movement whereas during MCP reactions the
      elbow flexion often appeared with a delay due to a brief co-contraction of the
      elbow flexor and extensor muscles which temporarily locked the elbow joint. The
      latter reaction was initiated by a backward/upward movement at the proximal
      joints accompanied by an ulnar deviation and a palmar flexion of the paw. The
      medio-lateral components of the movement were also clearly different in LCP and
      MCP reactions, both at the proximal and distal joints. The results indicate that
      various strategies of movement are used in CP reactions depending on the site of
      tactile stimulation.

PMID- 9033127
TI  - Sex and strain differences of acoustic startle reaction development in adolescent
      albino Wistar and hooded rats.
AB  - Acoustic startle responses (ASR) were studied in 12 young Wistar albino and in 15
      hooded rats of both genders. The six week old animals were first exposed to a 6.9
      kHz tone pair of 2 ms pulses of 120 db intensity with the inter-stimulus interval
      (ISI) between 2 and 11 ms. ASR amplitudes and latencies as a function of the ISI,
      animal strain and gender were recorded and analyzed for ten consecutive weeks. No
      differences in the ASR amplitude between Wistar and hooded rats were found. ASR
      amplitude increased during the experimental period and followed body weight
      increase. Significant differences were also observed between male and female rats
      in their startle responses to acoustic stimuli. Generally, male subjects
      responded with a greater ASR amplitude than females, and the changes may be
      attributed to the difference in neuromuscular development between genders. This
      experiment sets a background for further developmental studies.

PMID- 9033128
TI  - Nonlinearities within the cat LGN cell receptive fields in simulated network with
      recurrent inhibition.
AB  - We investigated the receptive fields of principal cells from the cat's lateral
      geniculate nucleus cells. About 20% of the X type neurones showed clear
      nonlinearities of summation when stimulated by two simultaneously onset, small
      bars of light. The possible source of this nonlinearity was studied on a
      specially designed model of a one-layer neuronal network with inhibitory,
      recurrent interactions, intended to mimic the inhibitory influence exerted on
      geniculate relay cells by perigeniculate interneurones. The model, when activated
      from periphery by two stimuli-like input patterns, produced at the output side
      the nonsymmetrical profiles of the receptive fields sensitivity, similar to those
      obtained in real experiments. This nonlinear output appeared when some of the
      relay cells were inhibited below their firing level threshold and this effect was
      spread through the network by lateral inhibitory connections. It is concluded
      that physiologically observed nonlinearities of the order of single receptive
      field mechanisms can be predicted by a simple recurrent network.

PMID- 9033129
TI  - 6-OHDA bilateral lesions to the central amygdala do not affect vasopressin
      improvement of recall in rats.
AB  - The influence of vasopressin (AVP) on recall of information in a passive
      avoidance situation after bilateral 6-OHDA lesions to the central amygdala was
      tested. AVP given 15 min before the retention testing at the icv dose of 1
      microgram significantly prolonged avoidance latencies both in lesioned and in
      sham-operated rats in comparison with the respective icv saline injected animals.
      Insignificant increase of spontaneous locomotor activity in rats lesioned to the
      central amygdala was unlikely to interfere with the cognitive effect of AVP.
      These results suggest that dopaminergic projection to the central amygdala is not
      responsible for the facilitatory effect of AVP on retrieval process in a passive
      avoidance situation.

PMID- 9033130
TI  - Auditory quality cues are more effective than auditory location cues in a R--no R
      (go--no go) differentiation: the extension of the rule to primitive mammals
      (American opossum, Didelphis virginiana).
AB  - Discrimination learning of instrumental responses to auditory compound stimuli
      was investigated in opossums using the R-no R (go-no go) differentiation. Each
      compound stimulus consisted of two factors: quality and location. Each correct
      response performed to the conditioned positive, or "safe" stimulus, was rewarded
      by food and never punished. Each incorrect response performed to the conditioned
      negative, or "warning" stimulus, was punished by an electric shock. In subsequent
      testing, each opossum proved to use only the quality cues to solve the task even
      though later testing showed them capable of using the location cues. Thus, the
      rule discovered in higher mammals, that the efficacy of auditory stimuli in
      differentiation depends on the perceptual ability of the animal as well as the
      type of the behavioral response with which the animal is confronted, may be
      extended to neurologically primitive mammals and also to a joint conditioned
      approach-avoidance method.

PMID- 9033131
TI  - Interhemispheric differences of sleep EEG complexity.
AB  - Complexity of EEG (omega), a global measure reflecting degree of spatial
      synchronization, was computed for whole night recordings of sleep EEG of 10
      healthy volunteers, 9 males and 1 female (age 21-53) and 6 depressive patients, 5
      males and 1 female (age 23-64). Sleep was scored visually in 20 s epochs, omega
      was calculated in 2.5 s segments and the median from 8 segments (20 s) was
      calculated. omega was calculated for the whole field of 21 electrodes and for the
      left and right hemisphere separately (2 x 8 electrodes). Measure of global power
      (sigma) and generalized frequency (phi) were also computed for the same data. In
      healthy subjects the complexity was higher over the right hemisphere during
      waking, and the difference shifted to higher complexity over the left hemisphere
      in slow wave sleep (F = 5.15, df1 = 4, df2 = 6856, P < 0.0005). The opposite
      trend was found in depressives (F = 10.51, df1 = 4, df2 = 3960, P < 0.0001).

PMID- 9033132
TI  - D2-dopamine receptor-mediated stimulation of inositol trisphosphate formation in
      chick retina.

PMID- 9033133
TI  - Postgraduate education in sedation--a new development.
AB  - Although demand for sedation courses has continued to increase, the traditionally
      theoretical format has tended to leave participants without the necessary
      clinical skills to practice sedation techniques with confidence. This article
      describes a new model of sedation course, introduced at Newcastle Dental Hospital
      and School, which has managed to overcome this problem.

PMID- 9033134
TI  - Non-evidence-based fluoride prescribing recommendations.

PMID- 9033135
TI  - Evidence-based assessment?

PMID- 9033136
TI  - Mechanism of tooth eruption.

PMID- 9033137
TI  - A case report or a cautionary tale?

PMID- 9033138
TI  - What injection?

PMID- 9033139
TI  - An evaluation of the diagnostic yield from bitewing radiographs of small
      approximal and occlusal carious lesions in a low prevalence sample in vitro using
      different film types and speeds.
AB  - AIM: To compare diagnostic yield in caries diagnosis from D- and E-speed films.
      DESIGN: A laboratory study. SETTING: A UK dental school between 1992 and 1994.
      MATERIALS AND METHODS: 96 extracted teeth containing approximal and occlusal
      lesions, but representing a low caries prevalence sample, were set in occluding
      dental arches. Bitewing radiographs were taken and interpreted by 5 examiners for
      the presence or absence of caries. Each examiner was also asked which film image
      he or she subjectively liked best. MAIN OUTCOME MEASURES: The teeth were
      subsequently sectioned and histologically examined to validate diagnostic
      decisions. RESULTS: For all film types the percentage of lesions with caries
      histologically in dentine correctly identified radiologically (sensitivity) was
      low (approximal caries 8-22%; occlusal caries 0-30%). The number of sound dentine
      sites correctly identified (specificity) was high (approximal caries 98-100%;
      occlusal caries 79-100%). There were no significant differences between D- and E
      speed films. Sensitivity was unaffected by each examiner's subjective preference
      for a particular film. The variation in sensitivity of diagnosis was due to
      differences between examiners. CONCLUSIONS: The reluctance of many GDPs to use E
      speed film because they 'do not like the image' cannot be endorsed or supported.
      Both E-speed film types examined can be recommended for use in general practice.

PMID- 9033140
TI  - Comparisons of the abilities of a neural network and three consultant oral
      surgeons to make decisions about third molar removal.
AB  - AIM: To compare the performance of a computer based decision support system (a
      neural network) and consultant oral and maxillofacial surgeons in making
      decisions about the need to remove lower third molars. DESIGN AND SETTING:
      Receiver operating characteristic (ROC) analysis at a hospital department of oral
      and maxillofacial surgery. SUBJECTS AND METHODS: Three consultant oral and
      maxillofacial surgeons indicated on a six-point rating scale how certain they
      were that each of 50 documented lower third molars required removal. Similar data
      were obtained from the neural network following appropriate coding of the
      clinical information. These data were compared with gold standard treatment
      decisions for each tooth based on National Institutes of Health Concensus
      criteria using ROC analysis. MAIN OUTCOME MEASURES: The area beneath each
      operator ROC curve (varying between zero and one with greater areas indicating
      better performance). RESULTS: The network performed as well a two consultants (P
      = 0.12/0.18, NS) and significantly better than the third (z = 526, P < 0.01).
      CONCLUSIONS: This work suggests that this computer based neural network could
      play a useful role in supporting dental practitioners making third molar referral
      decisions.

PMID- 9033142
TI  - Secondary retention of multiple permanent teeth.
AB  - An unusual case of secondary retention of multiple permanent teeth is reported.
      The clinical, radiographic and histological findings associated with this
      condition, and its management, are discussed.

PMID- 9033141
TI  - An evaluation of practice leaflets provided by general dental practitioners
      working in multi-racial areas.
AB  - AIM: The aim of this study was to assess the quality of information leaflets
      produced by NHS dental practices based in high density multi-racial areas within
      the city of Birmingham. METHOD: All of the 41 general dental practices based in
      ten Birmingham electoral wards with high concentrations of ethnic minorities were
      approached for a copy of their practice leaflet. Each leaflet was assessed in
      terms of: 1. overall presentation, 2. general information, and 3. information
      specifically relevant to the ethnic minorities. RESULTS: Seventy-eight per cent
      (32) of practices currently produce information leaflets. Compliance with
      specific NHS regulations ranged from 3% to 97%; 41% (13) of leaflets had one or
      more sections written in a minority language. Although ethnic minority languages
      were spoken by staff in three-quarters of the practices, less than one third
      specified this. Only one leaflet contained information on arrangements for non
      English speaking patients. CONCLUSION: Recommendations are made concerning the
      quality and content of practice leaflets for practices based in high density
      multi-racial areas.

PMID- 9033143
TI  - Toothache--the 'hell of all diseases'.
AB  - Last year was the bicentenary of the death of Robert Burns, who is Scotland's
      best known poet. January 25, Burns' birth date, is also a well-known celebration
      to the Scottish-the famous 'Burns Night'. Burns wrote many songs and poems, but
      his 'Address to the Toothache' is of particular interest to dentists. The poem
      provides a vivid account of one man's experience of toothache and gives an
      insight into how people regarded pain two hundred years ago.

PMID- 9033144
TI  - In memoriam: Robert Tiffany 1942-1993. Introduction to the Robert Tiffany
      Lecture.

PMID- 9033145
TI  - Beyond survival rates and side effects: cancer nursing as therapy. The Robert
      Tiffany Lecture. 9th International Conference on Cancer Nursing, Brighton, UK,
      August 1996.
AB  - Survival rates and side effects have become the dominant constructs of cancer
      treatment and care, to the detriment of more supportive and patient-focused
      approaches. The concept of quality of life introduced to address this has failed
      to temper the language of oncology. Here an argument is made for the place of
      cancer nursing as a therapeutic enterprise in its own right, which warrants much
      greater recognition. Clear evidence for the therapeutic effects of cancer nursing
      intervention from a series of meta-analyses of cancer nursing interventions
      exists. Cancer nursing as therapy has the potential to operate on four levels and
      can effect radical change by reconstructing care, cancer services, and wider
      health care environments so that they are much more patient focused and offer
      nursing therapy as an integral part of care. These include fundamental knowledge
      or theory generation for therapeutic practice, therapeutic interventions for
      individuals or problems, developing and changing health systems or environments,
      or critique and reconstruction of care from a societal perspective. The features
      of cancer nursing as therapy can be identified and are described. Cancer nurses
      are encouraged to take up the challenge offered by the concept of therapeutic
      cancer nursing so that its potential for nurses, patients, and cancer services
      can be realised.

PMID- 9033146
TI  - Taking care: caregiving to persons with cancer and AIDS.
AB  - The purpose of this study was to provide an in-depth description of Taking Care,
      one of the phases of a grounded theory (The Labor of Caregiving) of caregiving
      for families experiencing life-threatening illnesses such as cancer and acquired
      immune deficiency syndrome (AIDS). In-depth interviews were conducted with 26
      family caregivers of persons with cancer and AIDS during a 4-month period.
      Grounded theory methodology served as the basis for data collection and analysis.
      Data were analyzed in terms of the strategies, consequences, and interactions
      involved in the caregiving experience. The strategies of Taking Care included
      these data themes: Managing the Illness, Facing and Preparing for Dying, and
      Managing the Environment. The consequences of Taking Care included the data
      themes Coming to Know One's Own Strength, and Personal Suffering. Interactions
      that occurred as a result of Taking Care included Responding to Family
      Relationship Issues, and Struggling with the Health Care System. Findings from
      this research reveal that family caregivers dedicate an enormous portion of their
      lives to caring for their ill family members. They experience their own form of
      suffering as they watch their loved one die. Some also find personal meaning in
      the experience and an awakening of their own strengths. One of the implications
      from these findings is the need for a partnership between health care
      professionals and the families providing care.

PMID- 9033147
TI  - Symptom distress and life situation in adolescents with cancer.
AB  - Having a life-threatening disease like cancer during adolescence poses a number
      of problems. The purpose of this study was to identify the adolescent's own
      experience of areas of the life situation affected by the disease and problems
      related to it. Ten adolescents with varying diagnoses and treatment were
      interviewed. They also completed a quantitative measurement of problems. The
      result shows eight domains and 24 subdomains influencing the experience of life
      situation. Those were disease and treatment (side effects, isolation, medical
      procedures), identification (others are ill, appearance), feelings and reactions
      (mood, self-image, meaning, hope), coping (positive thinking, distraction,
      positive effects), togetherness (family, friends, school), support (family and
      friends, the youth association, professional support), reactions of the families
      (parents, siblings), and quality of care (professionalism, information,
      organization, equipment). The problems mentioned in the interviews are also
      compared with the quantitative measurement used. The adolescents mentioned 77
      problems in the interviews, of which 17 were not on the list of problems. Of
      those 17, seven dealt with physical problems, and six were problems concerning
      the quality of care. They ranked wanting and depending on parents as the worst
      problems for themselves from the list of problems.

PMID- 9033148
TI  - Effect of attitudes and subjective norms on intention to provide oral care to
      patients receiving antineoplastic chemotherapy.
AB  - The Theory of Reasoned Action (TRA) served as the conceptual framework for this
      study, which was designed to examine the effect of attitudes and subjective norms
      on intention to provide oral care for patients receiving chemotherapy. The
      sample, stratified by type of health care facility, consisted of staff nurses (N
      = 85) who work in oncology settings in New York State. Data were collected by
      sending 10 questionnaires to a designee at the randomly chosen facility. Both
      attitudes and subjective norms were significant predictors of behavioral
      intention, predicting 39% of the variance. Using the strategy devised by
      Laschinger and Goldenberg, the sample was divided into two groups: those that
      scored below the mean on behavioral intention (nonintenders) and those above the
      mean (intenders). Nonintenders scored significantly lower on attitudes and
      subjective norms than intenders. The TRA was not supported when examining the
      data of the nonintenders, whereas for the intenders the theory did operate as
      designed, predicting 23% of the variance in behavioral intention.

PMID- 9033149
TI  - Social support and breast self-examination.
AB  - Declining practice of breast self-examination (BSE) among women over the age of
      55 years dramatically decreases the probability of early detection of breast
      cancer. About two-thirds of women who die of breast cancer are over the age of 55
      years. Social support has been found to be associated with health behaviors.
      Although a woman's health may benefit from supportive relationships, the effect
      of diminished social networks on practices of BSE among older women has not been
      examined. Thus, the purpose of this study was to determine the relationship
      between social support and the frequency and accuracy of BSE practice. The sample
      consisted of 22 women, 55 years of age and older, who were having routine
      examinations at a small Midwestern gynecologic clinic. Social support was
      assessed by the Norbeck Social Support Questionnaire, and two tools assessed the
      accuracy and frequency of BSE. Social support was found to be significantly
      related to the frequency of BSE (r = 0.45, p < 0.05), but not to the accuracy of
      BSE (r = 0.28). The results also indicated that these women had lower social
      support scores compared with younger women. Planners of nursing intervention for
      BSE should consider health care providers as important resources in social
      support networks for the reinforcement of frequency and accuracy of BSE for older
      women.

PMID- 9033150
TI  - A peer education model for teaching breast self-examination to undergraduate
      college women.
AB  - The incidence of breast cancer in women continues to rise, and there is no known
      cause or prevention. Additionally, > 70% of all diagnosed breast cancer has no
      known risk factor involved. Early detection is mandatory for survival from this
      disease, but only three imperfect methods are available: mammography, clinical
      examination, and breast self-examination (BSE). One-third of all breast cancer
      cases occur in women under the age of 50 years, and this is a period when
      mammography is ineffective and clinical examination is infrequent. Consequently,
      BSE is highly significant for this age group. However, women do not perform BSE
      on a consistent monthly basis. The significant developmental characteristic of
      late adolescence and young adulthood is the formation of a personal identity.
      This age group is also heavily influenced by their peers. Therefore, a BSE
      program that incorporates peer education and elements essential to positive
      identity formation may be an effective means to establishing BSE as a normal
      health routine in young women.

PMID- 9033151
TI  - The Human Genome Project.

PMID- 9033152
TI  - Evaluating performance and change in mental health systems serving children and
      youth: an interorganizational network approach.
AB  - Planning for the delivery of community mental health services has evolved from
      models of services within individual agencies to community-wide systems of care,
      but development of methodologies for assessing system performance has lagged
      behind. This article presents one approach to system-level assessment by viewing
      children's mental health systems as an interorganizational network. Data are
      presented on two county-based child mental health systems in North Carolina that
      participated in the Robert Wood Johnson Foundation Mental Health Services Program
      for Youth. Site-specific data on client referrals, fund exchanges, and
      information flows were collected at two time points (1991 and 1993) to measure
      the cohesiveness and concentration of the service system using network k-core
      analyses. In addition, stakeholder ratings of service adequacy, quality,
      availability, coordination, and overall demonstration project goal attainment
      were obtained at both time periods. Findings indicate that the rural system was
      outperforming the urban system at the time of the first survey, but the urban
      system caught up over the study interval. There was high agreement between the
      network and stakeholder ratings of system performance at both time periods. The
      method of data collection and analysis used in this study provides tools that can
      be used in a variety of settings to assess service system growth and development.

PMID- 9033153
TI  - Treatment participation and outcome among problem drinkers in a managed care
      alcohol outpatient treatment program.
AB  - This article uses Markov analysis to investigate patterns of treatment
      participation of 361 patients treated in the alcohol and drug abuse programs of a
      large group model Health Maintenance Organization (HMO) to examine how
      participation is related to abstinence. Findings indicate that 82% of the
      patients in treatment one month after intake were in treatment three months
      later, and treatment retention dropped to 46% by month 6. Findings also indicate
      that 74% of patients abstinent and in treatment at month 1 remained so at month
      3. Abstinence at the first three-month interval was a strong predictor of
      abstinence at later time periods. A multivariate analysis showed that an
      expressed desire to stop alcohol use upon entry into treatment was the most
      consistent predictor of both treatment participation and abstinence at most time
      points. Treatment participation was also a significant predictor of abstinence.

PMID- 9033155
TI  - Institutional factors of nursing homes that predict the provision of mental
      health services.
AB  - This article explores the likelihood of the provision of mental health services
      in a nursing home as a function of the home's institutional factors. Data from
      the Institutional Population Component of the National Medical Expenditure Survey
      were used, and a modified model of equilibrium quality and price in a
      multivariate logistic framework is employed. The results indicate that meeting
      the demands for active mental health treatment, as mandated by the Nursing Home
      Reform Act of 1987, may be more difficult in those institutions that are part of
      a chain, are small, or contain Medicaid skilled nursing facility beds.

PMID- 9033154
TI  - The ethical challenges of a randomized controlled trial of involuntary outpatient
      commitment.
AB  - Involuntary outpatient commitment (OPC) is a civil justice procedure intended to
      enhance compliance with community mental health treatment, to improve
      functioning, and to reduce recurrent dangerousness and hospital recidivism. The
      research literature on OPC indicates that it appears to improve outcomes in rates
      of rehospitalization and length of stay. However, all studies to date have
      serious methodological limitations because of selection bias; lack of
      specification of target populations; unclear operationalization of OPC;
      unmeasured variability in type, frequency, and intensity of treatment; as well as
      other confounding factors. To address limitations in these studies, the authors
      designed a randomized controlled trial (RCT) of OPC, combined with community
      based case management, which is now under way in North Carolina. This article
      describes ethical dilemmas in designing and implementing an RCT of a legally
      coercive intervention in community-based settings. These ethical dilemmas
      challenge the experimental validity of an RCT but can be successfully addressed
      with careful planning and negotiation.

PMID- 9033156
TI  - Services for clients of community support programs in rural Wisconsin.
AB  - To improve understanding of services provided or coordinated by rural community
      support programs (CSPs) for people with severe mental illness, this article
      identifies services most used by clients and the amounts of services used. Data
      on publicly funded services for more than 900 clients in 13 rural CSPs in a
      midwestern state have been analyzed. Virtually all clients were Caucasian.
      Information about types and amounts of client services for 12 consecutive months
      was obtained from county information systems, local records, and Medicaid claims.
      Most CSP clients use case management, community support, medication checks,
      counseling, and medication counseling services. Much smaller percentages use
      other outpatient, residential, vocational, and inpatient services. Significant
      amounts of only two services, case management and community support, are
      reported. The findings emphasize the ability of rural mental health providers to
      supply general services, but some limitation in provision of specialized services
      and facilities.

PMID- 9033157
TI  - The appropriate role for the state hospital.
AB  - This article explores the role of the state hospital in providing long-term care.
      It is argued that long-term care is an important part of a mental health system,
      specifically for people with severe mental illness. The state hospital can be
      made to function more efficiently and also provide needed long-term care.

PMID- 9033158
TI  - The market for residential and day schools for children with severe emotional
      disturbance.
AB  - This article describes the market for residential and day programs that provide
      education and treatment services on site for children with severe emotional
      disturbance (SED) in terms of the market's size, cost, and ownership mix. As
      policymakers encourage integration of services across sectors, this research
      fills a gap in the mental health services literature by providing a baseline of
      information on facilities from the education sector. Data are used from a
      national, stratified sample survey of separate day and residential schools for
      children with handicaps conducted by the Department of Education. There are 1,523
      facilities providing educational and treatment services to 117,720 children with
      SED. Over half of the facilities are nonprofit, one-third are public, and less
      than one-tenth are for-profit. These programs represent a significant market of
      services for children with SED. Substantial differences in cost exist across
      ownership form that cannot be attributed to differences in size of facility or
      case mix of children enrolled.

PMID- 9033159
TI  - Physical illness among all discharged psychiatric inpatients in a national case
      register.
AB  - Previous studies have found that although psychiatric patients tend to have more
      physical illness than the rest of the population, it frequently goes unrecognized
      and untreated in psychiatric settings. This study investigated rates of reported
      physical illness among hospitalized psychiatric patients in preparation for
      national reform in mental health services. Data from the Israeli National
      Psychiatric Case Registry were analyzed on reported physical illness among all
      38,714 psychiatric discharges during 1989-1991. Physical illness was reported for
      10.62% of patients under age 25, 14.04% of patients 25 to 44, 34.27% of patients
      45 to 65, and 61.26% of patients 65 and older. Rates differed among hospitals.
      Reported physical illness was considerably lower than expected as compared with
      other studies. Underdiagnosis is suggested as a possible explanation. Study
      results were used to add differential payment for physical comorbidity under the
      new National Health Insurance Law. Other corrective measures are discussed.

PMID- 9033160
TI  - Sedative-hypnotic use by the elderly: effects on hospital length of stay and
      costs.
AB  - Sedative-hypnotic medications are often used to treat anxiety and sleep
      disorders, although they may not be used appropriately. Relationships between
      hospital length of stay (LOS), costs, and levels of sedative-hypnotic use were
      examined. Charts of 856 elderly patients were reviewed for sedative hypnotic use
      and categorized into three groups: those whose use exceeded Health Care Financing
      Administration (HCFA) guidelines, those who used sedative-hypnotic medications
      but did not exceed HCFA guidelines, and those who did not receive any sedative
      hypnotic medications. Patients whose sedative-hypnotic use exceeded guidelines
      had longer LOS (21.5 exceeding guidelines vs. 12.3 within guidelines vs. 6.7 no
      use, p < or = .001) and higher costs ($29,245 exceeding guidelines vs. $15,219
      within guidelines vs. $7,516 no use, p < = or .001.) Even after controlling for
      severity of illness and comorbid conditions, differences in LOS and costs
      persisted. This study indicates that sedative-hypnotic medications are frequently
      prescribed to elderly patients, often in doses exceeding proposed guidelines, and
      are associated with longer hospital stays and higher hospital costs.

PMID- 9033161
TI  - Use of psychiatric services by homeless veterans.
AB  - Patients treated in a Department of Veterans Affairs (VA) emergency room were
      evaluated to delineate the differences in use of services between homeless and
      domiciled veterans who have mental disorders. Data were obtained and compared on
      DSM-III-R diagnoses, number of hospitalizations, lengths of stay, and outpatient
      visits in the preceding year. Homeless veterans with mental disorders were
      significantly more likely to have emergency visits and psychiatric admissions in
      the preceding 12 months than were the domiciled veterans. However, the average
      length of stay was shorter for the homeless group. These differences must be
      accounted for in the design of programs targeting homeless veterans with mental
      illness.

PMID- 9033162
TI  - Residency training in Massachusetts: a new approach to state-university
      collaboration.
AB  - Traditional state-university collaborations, known as public-academic liaisons
      (PALs), have resulted in improved quality of service and enhanced residency
      training. Recent national trends for treating persons with serious mental
      illness, including moving services from institutional settings to community-based
      care and emphasizing the use of rehabilitative approaches as well as changes in
      the health care delivery system itself, have led to preliminary rethinking of
      some discrete aspects of more traditional approaches. Rather than discrete
      changes, Massachusetts has responded to these emerging trends with a new and
      comprehensive initiative that emphasizes one set of statewide standards in these
      emerging content areas for all residency training programs. Consistent with new
      practices in health care delivery, this new initiative was fielded through a
      process of competitive bidding rather than through traditional allocation of
      service positions. The development, implementation, and initial outcomes of this
      new approach are presented and implications for mental health administrators are
      discussed.

PMID- 9033163
TI  - Genetics and women's health.

PMID- 9033164
TI  - The Human Genome Project: view from the National Institutes of Health.
AB  - Because nearly all human disease is influenced by heritable alterations in the
      structure or function of genes, the issues and principles of medical genetics are
      coming to bear across medical disciplines. This "genetics revolution" is driven
      by the rapid pace in which scientists are identifying and isolating genes linked
      to human disease and is a direct outcome of the Human Genome Project. DNA tests
      are proving to be the most immediate commercial application of gene discovery,
      and the one seen most frequently by clinicians. To handle the growing populations
      who will seek genetic technologies as part of their health care, services must be
      expanded to help guide patients through the testing process so they make informed
      decisions about genetic testing. Care-givers will need to know not only about the
      medical benefits and risks of genetic technologies, but also about the
      psychosocial and legal implications of these technologies in the public arena.
      Until these issues are resolved, the technical ability to perform tests for DNA
      mutations should not be confused with a mandate to offer them. Safeguards must be
      in place to ensure that these tests are used wisely, maximizing their potential
      benefits to patients and minimizing their potential risks.

PMID- 9033165
TI  - The Human Genome Project: view from the Department of Energy.
AB  - The Human Genome Project (HGP), a research effort initiated by the Department of
      Energy (DOE) and jointly managed by the National Institutes of Health (NIH) and
      the DOE, will determine a representative (but complete) sequence of the DNA from
      a typical human cell. This information and the associated resources will help us
      understand the critical differences that make us individuals and lead to insights
      into many areas of medicine, biology, and biotechnology. The HGP was conceived
      because DOE and its predecessor agencies had a longstanding interest in
      developing more sensitive methods to detect genetic changes induced by ionizing
      radiation and to understand the related health effects. Additionally, the unique
      capabilities and resources of the DOE national laboratory system, including a
      multidisciplinary research environment, high-skill engineering and high
      performance computing centers fostered the ideal conditions for the success of
      such an ambitious undertaking. Knowing the human genome will revolutionize the
      practice of biology in the next century with far-reaching implications to health
      care and sustainable development. In a novel departure from previous science
      programs, the Human Genome Project includes a subprogram devoted to the ethical,
      legal, and societal implications (ELSI) of human genome research.

PMID- 9033166
TI  - Clinical molecular genetic testing.
AB  - Recent advances in human molecular genetics are rapidly producing clinical
      genetic tests for a variety of conditions. In addition to tests for rare genetic
      disorders, tests for common illnesses with mixed genetic and environmental
      etiologies are being developed. While practice guidelines for test utilization
      are being developed, many physicians would benefit from additional knowledge
      about the design and limitations of these tests. This article reviews the genetic
      background necessary to understand linkage-based and direct mutations tests and
      discusses some of the issues physicians must consider when selecting an
      appropriate test for a given clinical situation.

PMID- 9033167
TI  - Genetic identification of children of the disappeared in Argentina.
AB  - During the military dictatorship that ruled Argentina between 1976 and 1983, the
      security forces engaged in well-planned repression that included the abduction,
      torture, and disappearance of thousands of dissidents. Repression spared neither
      children nor pregnant women. Approximately 220 babies and children of the
      disappeared victims were abducted and kept mostly by families with connections
      with the military. After the restoration of democracy, attempts to find and
      identify the missing children were made, with the goal of restoring their
      personal and familial identities and returning them to their surviving relatives.
      The Association of Grandmothers of Plaza de Mayo and a number of geneticists who
      developed and applied methods of genetic identification to this human rights
      cause were instrumental in this quest. Initial use of histocompatibility (HLA)
      typing for genetic identification was later followed by nuclear DNA typing and
      mitochondrial DNA sequencing. Of 56 children found and identified, 30 were
      returned to their legitimate families, 13 remained with the families who had
      adopted them in good faith, 6 are still the subject of custody litigation in the
      courts, and 7 were found dead. Psychological and ethical guidelines protecting
      the best interests of the children were followed in all proceedings.

PMID- 9033168
TI  - Genetic susceptibility testing for breast and ovarian cancer: a progress report.
AB  - The recent identification of genes that predispose their carriers to breast and
      ovarian cancer promises to shed light on the biology of cancer susceptibility.
      Individuals with mutations in the BRCA1 gene on chromosome 17 and the BRCA2 gene
      on chromosome 13 have four to eight times the risk of developing breast cancer as
      women in the general population. The many mutations that have been identified in
      both genes are predicted to produce a truncated, presumably nonfunctional,
      protein. Individuals of Ashkenazi Jewish decent have been found to carry specific
      BRCA1 and BRCA2 mutations. The sequences of BRCA1 and BRCA2 are not similar to
      any other previously cloned genes. Investigations are underway to elucidate the
      biological function of these genes. In the meantime, these genes offer the
      opportunity for members of high incidence cancer families to decide whether to
      undergo predisposition testing. There is a paucity of data to guide physicians in
      making follow-up recommendations to those who are found to be carrying a
      mutation. Thus, decisions about testing are personal and demand pretest education
      and counseling about the risks, benefits, and limitations. Further research into
      testing decisions and their outcome is greatly needed.

PMID- 9033170
TI  - Genetic counseling and prenatal diagnosis: a multicultural perspective.
AB  - More and more women are using prenatal tests to obtain specific information on
      the health of the developing fetus. The objective of genetic counseling is not to
      decrease the occurrence of genetic disease, it is to help individuals and
      families adjust to their genetic risks and make their own decisions in line with
      their reproductive goals and world views. Choices made by parent(s) will reflect
      their own intrapsychic processes as well as their own cultural and social
      understanding of genetic risk and disease. As prenatal testing continues to
      diagnose an ever growing number of genetic disorders, genetic counseling faces
      greater and greater challenges. Now more than ever before, genetic counseling
      must incorporate both psychological counseling and multiculturalism in order to
      serve diverse individuals and families at risk for genetic disease.

PMID- 9033169
TI  - Communicating about chromosomes: patients, providers, and cultural assumptions.
AB  - Field-based anthropological research on the social impact and cultural meaning of
      prenatal diagnosis suggests four factors that contribute to multicultural patient
      provider miscommunication. These are: 1) the detection of fetal mental
      retardation, particularly Down syndrome, is not always an appropriate reason to
      test; 2) the statistical information on age-related risk rates for chromosome
      abnormality may appear small when compared to more pressing vulnerabilities faced
      by poor and/or immigrant pregnant women and their families; 3) variation in
      individual reproductive histories and social values strongly shape acceptance and
      rejection of the test; and 4) most controversially, not everyone accepts the
      burdens of individual choice.

PMID- 9033171
TI  - Is there a "women's ethic" in genetics: a 37-nation survey of providers.
AB  - The ethical views of 2,903 geneticists in 37 nations were surveyed and compared
      by gender. Women made up about half the physicians and PhDs and the great
      majority of genetic counselors. US women physicians differed from men physicians
      on 13% of 491 ethical questions; genetic counselors differed from all MDs on 60%
      and from women MDs on 46%. Women physicians were similar to men in directiveness
      and most counseling after prenatal diagnosis. More women would refer for sex
      selection, more would warn a patient's relatives of genetic risks against the
      patient's wishes, and fewer would test children for genes for adult-onset
      disorders. Genetic counselors were less directive than physicians, more likely to
      preserve confidentiality, and less willing themselves to abort. Outside the
      United States, women physicians differed from men 43% of the time; they were more
      directive than men, more pessimistic about disabilities, more willing to abort
      fetuses with genetic disorders, and more likely to place the health of potential
      children or the welfare of family above parental autonomy. No universal "women's
      ethic" emerged from the study; culture and professional locus affected views more
      than gender.

PMID- 9033172
TI  - Compromised consent: deficiencies in the consent process for genetic testing.
AB  - Genetic tests are available for an increasing array of disorders. Although the
      doctrine of informed consent requires that physicians provide sufficient
      information to patients in advance of testing and allow them to make decisions in
      a noncoerced way, some studies have shown that physicians do not provide adequate
      information about the nature of genetic testing and its risks. Some physicians
      test patients without their consent. This article recommends that physicians
      address the limitations on their knowledge about genetics and about life with
      genetic disorders. It also analyzes how the informed consent process for genetic
      testing can be improved.

PMID- 9033173
TI  - Genetic discrimination and health insurance: a call for legislative action.
AB  - Fear of genetic discrimination in health insurance is a growing reality.
      Individuals who might otherwise choose genetic testing may decline it based on
      their fear that they or their family members will not be able to obtain or
      maintain health insurance coverage. This commentary notes the evolving
      legislative efforts to address genetic discrimination in health insurance and
      urges physicians to help move this legislative agenda forward.

PMID- 9033174
TI  - The revival of eugenics in American popular culture.
AB  - This paper explores the possibility of a "new eugenics" from the perspective of
      American popular culture. Several related ideas have been expressed in recent
      popular sources: differential rates of reproduction among different groups are
      threatening the future; there are "lives not worth living"; and the threats of
      disability are sufficient to justify limiting reproductive rights. These beliefs
      draw on assumptions that the future will depend on controlling the genetic
      constitution of the species. Popular ideas about the powers of the gene, we
      argue, are laying the basis for policies controlling reproduction for the common
      good.

PMID- 9033175
TI  - Prognostic significance of altered cerebral blood flow velocity in acute head
      trauma.
AB  - From July 1992 to January 1993, 31 patients with acute closed head injuries
      underwent blood flow velocity (BFV) measurement in the middle cerebral artery by
      transcranial Doppler ultrasound. Eighteen patients had abnormal changes of BFV
      (group A) and 13 patients had normal BFV (group B). In group A, there were eight
      deaths (44%) and the Glasgow Outcome Scale score was 2.6 +/- 0.4 (mean +/- SEM).
      On admission, 14 group A patients had decreased BFV, including nine patients with
      evidence of early cerebral circulatory arrest (CCA). During hospitalization,
      eight group. A patients were diagnosed with global hyperemia, including two
      patients who had early CCA. Another six in group A had ultrasound recordings
      consistent with vasospasm, and three of these six also experienced early CCA. The
      renaming four patients in group A had persistently low BFV, progressing from
      early CCA. In group B there were two deaths (15%) and the mean Glasgow Outcome
      Scale score was 4.0 +/- 0.5. Group A had higher mortality (Fisher's exact test, p
      = 0.128) and a significantly higher rate of unfavorable functional outcome than
      group B. To evaluate the prognostic significance of these BFV changes, group A
      was subdivided into global hyperemia, vasopasm and early CCA subgroups. Both the
      vasospasm and early CCA subgroups had significantly lower Glasgow Coma Scale
      scores on admission and a higher rate of unfavorable functional outcomes than
      group B. All five survivors with vasospasm and/or early CCA showed ischemic
      morbidity on follow-up cranial computed tomography; though those with global
      hyperemia did not. There were no significant differences in the Glasgow Coma
      Scale score on admission, mortality or functional outcome between global
      hyperemia patients and group B patients. Global hyperemia may represent a
      recovery stage of impaired cerebral hemodynamics. This stage may occur
      transiently and has no major impact on morbidity or mortality. Vasospasm and
      early CCA may be closely related to ischemic complications, and may provide
      clinical information for selecting appropriate therapy in acute head trauma.

PMID- 9033176
TI  - In vitro activity of ofloxacin against Mycobacterium tuberculosis.
AB  - For the past 3 years, ofloxacin has been widely used in treating patients with
      drug-resistant tuberculosis in Taiwan. To study its usefulness in treating these
      patients, 139 isolates of Mycobacterium tuberculosis from patients treated at the
      Taiwan Provincial Chronic Disease Control Bureau from September 1994 to September
      1995 were tested to determine the in vitro antituberculosis activity of
      ofloxacin. Of these, 131 had not been previously exposed to ofloxacin, and 130
      (99.2%) were susceptible to ofloxacin. Sixty-four isolates were found to be
      susceptible to all conventional antituberculosis drugs, and all of these were
      also susceptible to ofloxacin. Of the remaining 67 isolates that were resistant
      to one or more conventional antituberculosis drugs, 66 (98.5%) were susceptible
      to ofloxacin. There was no association between susceptibility to ofloxacin and
      susceptibility to conventional antituberculosis drugs among the isolates tested.
      Of the eight isolates of M. tuberculosis previously exposed to ofloxacin, seven
      (87.5%) were resistant. Our results indicate that patients with multidrug
      resistant strains of M. tuberculosis who have not received prior ofloxacin
      treatment may be safely treated with ofloxacin even without knowing the result of
      pretreatment ofloxacin susceptibility tests. We also found that ofloxacin
      resistance emerges frequently. Therefore, an adequate combination of
      antituberculosis drugs, along with ofloxacin, should be prescribed to prevent the
      development of resistance to ofloxacin.

PMID- 9033177
TI  - Biochemical events associated with ligation of the common bile duct in Wistar
      rats.
AB  - Oxygen free radicals have been implicated as mediators of tissue injury in a
      variety of diseases. We investigated the role of oxidative injury and oxygen free
      radical scavengers in liver cell injury associated with obstructive jaundice in
      Wistar rats. Bile duct ligation for 4 or 7 days led to a decrease in both vitamin
      E and A in the plasma and liver of male Wistar rats, indicating the malabsorption
      of lipid-soluble vitamins. Serum bilirubin, alkaline phosphatase and gamma
      glutamyl transpeptidase activities were increased in the bile-duct-ligated rats.
      Furthermore, marked increases in lipid peroxide and oxidized glutathione levels
      indicated cholestatic liver injury. The antioxidant defense system was impaired,
      as shown by decreases in reduced glutathione and in the activities of glutathione
      peroxidase (GSH-Px) and superoxide dismutase. Moreover, these high lipid peroxide
      levels and low levels of antioxidants correlated with the severity of jaundice.
      After releasing the bile duct ligation, levels of bilirubin, lipid peroxide and
      oxidized glutathione declined, while the levels of vitamin E and A, reduced
      glutathione, and the activities of GSH-Px increased, indicating an improvement in
      liver function. These findings suggest that lipid peroxidation is associated with
      the pathogenesis of liver damage in animals with bile duct ligation. Meanwhile,
      free oxygen radical scavengers are reduced in the bile-duct-ligated rats, thereby
      increasing the susceptibility of the liver to injury by oxygen-derived free
      radicals.

PMID- 9033178
TI  - Comparison of bone transport and bone graft methods in the experimental treatment
      of bone defects.
AB  - Large segmental bone defects due to trauma, infection or tumor resection are
      difficult to treat. To compare the effects of a bone transport technique with
      various bone graft methods in treating this problem, an animal model with a
      designed mini external fixator to accomplish the bone transport was established.
      New Zealand white rabbits weighing 3 kg were divided into five groups. A 2 cm
      bone defect was created in the left hind tibia of each rabbit, then stabilized
      with an external fixator. In the control group, no treatment was given. In the
      autograft group, an autogenous bone segment was repositioned after removal of the
      periosteum. In the double osteotomy group, the tibial shaft was doubly
      osteotomized at the upper and lower level with preservation of vascular supply to
      the middle segment. In the allograft group, a deep-frozen allograft was put into
      the defect and in the bone transport group, the middle segment of the tibia was
      transported downward gradually beginning 1 week after the osteotomy. The rabbits
      had weekly radiographic examinations and were killed 3 months postoperatively.
      Rabbits with fractures, severe infection, incomplete osteotomy or that died were
      excluded from analysis. There were 12 rabbits remaining in each group. Results
      were evaluated by radiographic and torsion tests. Rabbits in the double osteotomy
      group had the best results, followed by the autograft bone transport, allograft
      and control groups. Fractures at the distal pin-bone interface occurred more
      often in control and bone transport groups than other groups. Incomplete
      osteotomy and problems at the docking site were specific to the bone transport
      group. The results of this study suggest that the bone transport technique may be
      used to treat large bone defects, but is associated with significant morbidity.

PMID- 9033179
TI  - Surgical treatment of clubfoot deformity in arthrogryposis multiplex congenita.
AB  - Clubfoot deformity in arthrogrypotic patients is difficult to correct, and its
      recurrence rate is high. We retrospectively reviewed 37 clubfeet in 20 patients
      with arthrogryposis multiplex congenita who were treated from 1984 to 1993. There
      were 11 males and nine females. Bilateral involvement was seen in 17 patients and
      unilateral involvement in three. The mean age at the initial surgery was 2.5
      years (range 4 mo to 25 yr). Soft tissue release alone was performed on 33 feet.
      Primary talectomy was done on both feet of one other patient. The remaining
      patient (two feet) underwent triple arthrodesis. Recurrence or residual
      deformities were seen in 18 feet with soft tissue release, among which 12 feet
      underwent secondary surgeries including soft tissue release, osteotomy, talectomy
      and connection with Ilizarov apparatus. After the secondary surgery, four of the
      12 feet still had deformities. One foot had a third surgery. Achilles tendon
      lengthening and osteotomy. Twenty-six feet were rated as having good results
      (plantigrade, painless and without obvious deformity), seven were rated fair
      (residual deformity requiring secondary procedures) and four had poor results
      (persistance or recurrence of clubfoot). Despite a high recurrence rate, clubfoot
      deformity in arthrogrypotic patients can be treated first with radical soft
      tissue release when the patient is less than 1 year of age. If the foot deformity
      is persistant or recurs, talectomy can achieve a plantigrade foot. Triple
      arthrodesis should be reserved for patients with a mature bony structure.

PMID- 9033180
TI  - Valgus osteotomy for congenital coxa vara.
AB  - Congenital coxa vara is a rare disease which can result in a significant
      disability if untreated or improperly treated. In this retrospective review of
      eight patients (12 hips) with congenital coxa vara, there were five boys and
      three girls. Four patients had bilateral involvement and four had unilateral
      involvement. At the time of surgery, the average age was 7.9 years. All patients
      underwent valgus intertrochanteric osteotomy with wires or blade-plates for
      fixation. The mean Hilgenreiner-epiphyseal angle was 75 degrees before surgery
      and improved to 25 degrees after surgery. The mean neck-shaft angle improved from
      95 degrees to 137 degrees immediately after the osteotomies and was 125 degrees
      at the final follow-up. At a minimum two year follow-up only three hips in three
      patients maintained more than 80% correction. These three patients all had
      developmental coxa vara. The acetabular depth improved significantly in the
      patients with developmental coxa vara, especially in two patients (three hips)
      who underwent surgery before 6 years of age. Closure of physeal plates was found
      in three patients (five hips) before surgery and occurred in two patients (two
      hips) after surgery. After surgery, only two patients had persistent soreness.
      One patient walked with a limp, and the other, with multiple epiphyseal dysplasia
      had significant leg length discrepancy. Our results show that valgus osteotomy
      can correct varus deformities of the proximal femur and improve function. If
      performed early, it can also prevent the development of hip dysplasia in patients
      with developmental coxa vara. However, the response of acetabular development was
      variable in patients with coxa vara due to skeletal dysplasia, despite valgus
      osteotomy.

PMID- 9033181
TI  - Ornithine transcarbamylase deficiency.
AB  - Two infants, one male and one female, with elevated serum ammonia levels, were
      shown, based on urine organic acid analysis and DNA studies, to have ornithine
      transcarbamylase (OTC) deficiency. OTC deficiency is one of the most common urea
      cycle disorders. Hyperammonemia occurred at 3 days of age in the male infant, and
      at approximately 7 days of age in the female infant. Administration of sodium
      benzoate and sodium phenylacetate lowered the serum ammonia level effectively in
      both cases. Other modalities, including peritoneal dialysis and protein
      restriction, were also important in the control of the serum ammonia level. The
      mother of the male infant was shown to be a carrier of the OTC gene mutation by
      allopurinol loading test. The mutation site of the OTC gene for the female infant
      was identified, but her mother did not have the mutation. OTC deficiency, an
      incompletely dominant X-linked disorder, is a severe disease even for females and
      prompt treatment and precise genetic counseling are mandatory.

PMID- 9033182
TI  - Primed in situ (PRINS) labeling for rapid detection of numeric and structural
      chromosome anomalies.
AB  - Primed in situ (PRINS) labeling has been applied to replace the traditional
      fluorescence in situ hybridization (FISH) method for the detection of specific
      sequences in situ in several numerical and structural chromosome anomalies. PRINS
      is based on sequence-specific annealing in situ of an unlabeled DNA probe or
      oligonucleotide primer. The probe serves as a primer for chain elongation in
      situ, using the labeled nucleotides as substrate. An oligonucleotide, (CCCTAA)
      representing human telomeric sequences, was mixed with nucleotides, biotin-16
      dUTP, and Taq DNA polymerase, and applied on metaphase slides with ring
      chromosomes 4, 13, 18, X and Y. Primers for alpha-satellite sequences specific
      for the centromeric regions of human chromosomes 13, 15, 18, X and Y were also
      used to characterize the nature and origin of unidentifiable supernumerary marker
      chromosomes. The specificity of PRINS in differentiating centromeric sequences of
      chromosome [3 from 21 which is not possible with FISH, was demonstrated. Absence
      of the telomeric sequences in all of the ring chromosomes was noted in normal and
      abnormal phenotypes. The results suggest a mechanism of ring formation, an end-to
      end fusion after loss of the palindromic nucleotide sequences at the telomeres
      PRINS, a fast and sensitive method of detecting nucleic acid sequences in situ,
      may be a reliable technique for detecting chromosomal aneuploidies and some
      structural rearrangements.

PMID- 9033183
TI  - Neuroimaging in intractable complex partial seizures.
AB  - We retrospectively analyzed 19 patients with intractable complex partial seizures
      who underwent temporal lobectomy and compared the usefulness of various imaging
      techniques in diagnosis and localization. Pathologic findings consistent with
      mesial temporal sclerosis were found in 12 patients arteriovenous malformations
      in four, tumors in three, and coexistence of a tumor and mesial temporal
      sclerosis in one. Electroencephalography and single photon emission computed
      tomography detected lateralized functional abnormality in two patients when
      computed tomography (CT) and magnetic resonance imaging (MRI) showed equivocal
      results. Both CT and MRI showed all arteriovenous malformations and tumors. CT
      detected only four cases of mesial temporal sclerosis, while MRI showed nine
      cases. Detection, delineation and diagnosis of lesions responsible for complex
      partial seizures are essential for good surgical results. Thus, the importance of
      image studies, especially MRI, should be emphasized in patients with complex
      partial seizures.

PMID- 9033184
TI  - Helicobacter pylori infection and risk of peptic ulcer among cirrhotic patients.
AB  - There is a higher prevalence of peptic ulcer disease in cirrhotic patients than
      in the general population. Whether Helicobacter pylori is a risk factor for
      peptic ulcer in cirrhosis remains controversial. The aim of this study was to
      determine whether there is a significant correlation between H.pylori infection
      and peptic ulcer in liver cirrhosis. In a cross-sectional study, 49 cirrhotic
      patients underwent upper gastrointestinal endoscopy and 75 controls (health
      examinees) without liver disease were also examined by endoscopy. The presence of
      H. pylori was assessed by culture, histologic findings and rapid urease test of
      gastric antrum biopsy specimens. Thirty of the 49 (61%) cirrhotic patients had
      peptic ulcers as compared to 24 of the 75 (32%) controls. The frequency of H.
      pylori in the antrum in the cirrhotic group was significantly lower than in the
      control group (39% vs 69%). The presence of H. pylori was more frequent in
      control patients with gastric (75%) and duodenal ulcers (95%) than nonulcer
      control patients (59%) whereas the difference between patients with peptic ulcer
      and nonulcer (40% vs 37%) was not significant in cirrhotic patients. H. pylori
      was identified in 40% of the cirrhotic patients with duodenal ulcers compared
      with 95% of controls with duodenal ulcers (p < 0.05). Nevertheless, this
      difference was not significant among patients with a gastric ulcer between the
      two groups (40% vs 75%). There was no significant difference in the frequency of
      H. pylori infection among nonulcer patients between the cirrhotic and control
      groups (37% vs 59%). In conclusion, we found no evidence to substantiate an
      etiologic role of H. pylori in the development of a duodenal ulcer in cirrhotic
      patients.

PMID- 9033186
TI  - ECG of the month. Two faces. Wide QRS complex tachycardia.

PMID- 9033185
TI  - Counseling clinic for pediatric weight reduction: program formulation and follow
      up.
AB  - The feasibility and efficacy of an outpatient-based multicomponent weight
      reduction program was tested with 68 consecutively enrolled obese children and
      adolescents. The patients were invited to participate in an individualized six
      session program that included parent involvement, diet education, exercise
      management and behavior modification by a culturally sensitive method. Fifty-six
      patients were followed up 1 year after treatment. Comparison at pretreatment, end
      of-treatment and 1-year-after-treatment with respect to changes in degree of
      obesity, measured by weight-for-length index (WLI), showed statistically
      significant differences. Ninety-seven percent of participants were below their
      pretreatment WLI at the end-of-treatment examination, and 80% at 1-year-after
      treatment follow-up. At 1-year-after-treatment, 59% showed a reduction in WLI of
      0.1 or more, as compared with 38% of participants at end-of-treatment. Two
      parameters previously considered predictors of successful weight control, notably
      age of participants and percentage of weight lost during treatment, were
      significantly associated with a reduction in the degree of obesity after one
      year. Although the long-term efficacy cannot be determined, our results indicated
      that this comprehensive weight reduction program may have an encouraging effect
      on the weight status of obese Chinese children and adolescents.

PMID- 9033187
TI  - Congenital aural atresia.
AB  - Congenital aural atresia is viewed by many physicians as a poorly characterized,
      arcane, clinical entity associated with a variety of hearing deficits. In fact,
      congenital aural atresia represents a disease spectrum predicated on the reliable
      embryological development of the first and second branchial apparatus. All
      degrees of microtia, canal atresia, and middle ear structure malformation are
      identified by this disease process. Many classification schemata have been
      proffered since the turn of the century to assist the otologist with a better
      means of assessing the patient's suitability as a surgical candidate. Clinical,
      audiological, and radiographic evaluation of congenital aural atresia is
      essential in selecting the appropriate candidates for surgery or hearing
      amplification. The high resolution CT scan has advanced the understanding and
      preoperative assessment of this condition. Surgical repair of the external ear
      and middle ear malformations is effective in properly selected patients.
      Essential background information, relevant embryology, patient evaluation,
      treatment, and current controversies related to congenital aural atresia are
      discussed.

PMID- 9033188
TI  - Radiology case of the month. Hip and back pain in the elderly. Stress injury of
      bone.

PMID- 9033189
TI  - The Journal 150 & 100 years ago. January 1847 and 1897.

PMID- 9033190
TI  - Legal issues in health care administration: what is important to the
      administrator?
AB  - Many legal questions are presented to hospital administrators daily. To determine
      the relative importance of their concerns, a questionnaire covering 57 legal
      issues was submitted to the administrators of all 196 Louisiana hospitals. The
      survey indicated that every issue was considered important, but some issues were
      considered very important. Sometimes the level of concern was influenced by the
      characteristics of the hospital, for example, size and ownership.

PMID- 9033191
TI  - Perineal repair of rectal prolapse.
AB  - Perineal approaches to the repair of rectal prolapse are frequently used in
      elderly or high-risk patients. These repairs have lower operative mortality and
      morbidity than intra-abdominal repairs but in general have higher recurrence
      rates. This study reviews our recent results with perineal prolapse repairs,
      briefly summarizes the literature, and discusses the available perineal
      operations. Eight patients (mean age 75 years) underwent surgical prolapse repair
      over an 18-month period. Treatment was by Altemeier's procedure (perineal
      rectosigmoidectomy) in 6 patients and Delorme's procedure in 2 patients. There
      were no operative mortalities, and an anastomotic dehiscence in 1 patient was
      managed nonoperatively. All patients with preoperative constipation improved and
      no patient reported worsening of continence. Surgical approaches from the
      perineum may be used in elderly and poor risk patients to treat rectal prolapse
      with low mortality and morbidity. These techniques have not adversely affected
      fecal continence and have improved symptoms of constipation with an acceptable
      rate of recurrence.

PMID- 9033192
TI  - High school football-related cervical spinal cord injuries in Louisiana: the
      athlete's perspective.
AB  - Louisiana has one of the highest rates in the nation of cervical spinal cord
      injuries to high school football players. When the national rate of these
      injuries is applied to the number of high school participants in Louisiana, we
      would expect there to be only one catastrophic neck injury every 14 years.
      Louisiana, however, has averaged 2.3 spinal cord injuries per year for the past
      seven football seasons. Players who use the top of their helmets to tackle,
      block, or strike opponents are at greatest risk for these injuries. This study
      was undertaken to describe the safe tackling knowledge, attitudes, and practices
      of Louisiana high school football players. We surveyed 596 players from 16
      Louisiana high schools. When asked if it was within the rules to tackle anyone by
      using the top of their helmet, 29% incorrectly answered "yes". Similarly, when
      asked if they had ever tackled anyone using the top of their helmet, 33% reported
      that they had. Twenty-eight percent said that they had been taught to use this
      unsafe method. Of these, 83% said that their coach taught them this dangerous and
      illegal method. Using the helmet as a battering ram must be discouraged.
      Education for officials, coaches, and players is needed to improve recognition of
      improper tackling. Proper training in tackling and blocking is an important means
      of minimizing the possibility of catastrophic injury.

PMID- 9033193
TI  - Surgical resection of endometriosis after prior hysterectomy.
AB  - Twenty-seven patients who underwent laparotomy after a prior hysterectomy for
      endometriosis were studied. The mean interval from index surgery to repeat
      surgery was 7.8 years. Abdominal/pelvic pain was the most common presenting
      complaint, followed by the objective finding of a pelvic mass. Six patients were
      taking estrogen replacement therapy. Physical findings suggested a pelvic mass or
      nodularity in 15 patients. Extensive pelvic adhesions with dense involvement of
      the ovaries was common. Surgery in 2 patients was complicated by an enterotomy,
      with 4 patients requiring a bowel resection and anastomosis. Postoperatively, 5
      patients developed fever, 3 a postoperative ileus, 1 a wound breakdown, and 1 a
      small bowel obstruction. The mean hospital stay was 5 days. We conclude that in
      patients who have undergone a hysterectomy as treatment for endometriosis,
      subsequent surgery to remove the ovaries involved with recurrent endometriosis
      carries considerable morbidity. In light of readily available estrogen
      replacement therapy, conservation of the ovaries in patients who are undergoing a
      hysterectomy for endometriosis should be applied with caution.

PMID- 9033194
TI  - An acute dystonic reaction with long-term use of ranitidine in an intensive care
      unit patient.
AB  - Dystonic reactions produce twisting and repetitive movements or abnormal
      posturing; this sign is considered an extrapyramidal sequela that is most
      typically thought to arise from decreased dopamine activity in the basal ganglia.
      Severe dystonic reactions have been shown to occur in concert with numerous
      medications. Although most commonly described with anti-psychotic agents such as
      haloperidol and phenothiazine, dystonic reactions have been observed in those who
      have used fluoxetine, erythromycin, crack cocaine, phenobarbital, cisapride, and
      buspirone. This report details the case of a patient who developed an acute
      dystonic reaction while taking ranitidine for peptic ulcer prophylaxis, a
      complication that, to our knowledge, has yet to be described with the use of this
      agent.

PMID- 9033195
TI  - Vaccination against leprosy--the view from 1996.

PMID- 9033196
TI  - The management of erythema nodosum leprosum: current and future options.

PMID- 9033197
TI  - Response to treatment by multidrug regimens in the THELEP controlled clinical
      drug trials. Subcommittee on Clinical Trials of the Chemotherapy of Leprosy
      (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme
      for Research and Training in Tropical Diseases.
AB  - During the period 1977-1983, clinical trials of five multidrug regimens were
      conducted among 215 patients with previously untreated multibacillary leprosy at
      the Institut Marchoux, Bamako, Mali, and the Central Leprosy Teaching and
      Research Institute, Chingleput, South India. The trials were designed primarily
      to permit measurement of the proportions of persisting Mycobacterium leprae in
      the patients' skin lesions. In addition, the combination of the large number of
      patients studied, the large volume of carefully standardized data, and the
      employment of multidrug regimens provided a unique opportunity to measure the
      clinical response of patients to treatment by these regimens. Persisting M.
      leprae were detected in 7.8% of all specimens; the frequency did not vary with
      centre, regimen, or duration of treatment. The bacterial index (BI) decreased by
      a mean annual rate of 75%, the logarithmic biopsy index by a mean annual rate of
      87%, and the logarithm10 number of acid-fast bacilli per g tissue by a mean
      annual rate of 69%. The rate of decrease of these measures of the numbers of M.
      leprae was related to the 'strength' of the regimen. Although no difference of
      clinical status as a function of regimen was demonstrated, a difference was
      observed between the two centres, probably the result of different clinical
      criteria employed by the responsible physicians. A change of histopathological
      classification in the course of the trials was recorded for 12% of the patients,
      most representing upgrading from LLs to BL, without relation to regimen or
      treatment centre. ENL was less severe for the patients treated by the maximal
      regimen in Chingleput, which included daily clofazimine; as expected, the
      majority of patients treated by this regimen were found to have maximal
      pigmentation. Prednisolone was evidently preferred for treatment of ENL in
      Chingleput, whereas thalidomide was preferred in Bamako. Fourteen cases of
      jaundice were observed, primarily among the patients treated by the maximal
      regimens, that included daily administration of rifampicin for the entire two
      years of the trials. Measurements of weight and blood pressure, and studies of
      the blood and of hepatic and urinary tract function revealed only negligible
      differences among regimens and between centres. In many cases, those differences
      that were observed were associated with ENL.

PMID- 9033198
TI  - Primary resistance to single and multiple drugs in leprosy--a mouse footpad
      study.
AB  - Skin biopsy homogenates obtained from three cases of lepromatous leprosy with no
      prior history of antileprosy treatment were tested in the mouse footpad for the
      sensitivity of Mycobacterium leprae to multiple drugs. One of the inocula was
      sensitive to all the three drugs tested using the highest concentration each of
      DDS 0.01 g%, RFP 0.03 g% and CLF 0.01 g%. The 2nd inocula showed growth in the
      presence of 0.01 g% DDS only. While the 3rd inocula (Pt. KU) tested resistant to
      all the three drugs in the first, i.e. man to mouse, as well as in the second
      passage, i.e. mouse to mouse.

PMID- 9033199
TI  - Borderline--tuberculoid leprosy: clinical and immunological heterogeneity.
AB  - The authors analysed some immunological criteria in leprosy patients diagnosed as
      borderline tuberculoid by the presentation of different grades of skin lesions as
      well as different grades of nerve involvement. Only 50% of the patients presented
      a single skin lesion and 58% had none or only one affected nerve. Nineteen
      patients (39.6%) showed a positive lepromin reaction (induration > or = 5 mm).
      Patients with a positive skin test had a greater number of skin lesions when
      compared with patients with a negative lepromin test. Fifty-seven percent of the
      patients were found to be positive using a lymphoproliferation test (LTT) in
      response to Mycobacterium leprae antigens. Positive LTT results did not correlate
      with the number of skin lesions, but patients unresponsive to LTT had a lesser
      extent of nerve involvement. Four out of 18 patients (22%) released high IFN
      gamma levels in PBMC culture stimulated by M. leprae. (mean U/ml +/- SD = 142 +/-
      72). All of these 4 patients presented only one skin lesion, although three of
      them had more than one affected nerve. Nineteen out of 21 patients (90.5%) showed
      no anti-PGL-1 antibodies in their serum. The low levels of anti-PGL-1 antibodies
      among these patients confirmed their tuberculoid background even in those with
      multiple skin lesions. These findings seem to attribute an important role to IFN
      gamma in restraining the spreading of the infection in the skin, but IFN gamma
      may have an opposite effect on the nerves. The potential pathological effects of
      IFN gamma during the delayed type of hypersensitivity can be related to its
      ability to synergise with other inflammatory cytokines such as TNF alpha, IL-1
      beta, and others.

PMID- 9033200
TI  - Nerve function impairment in leprosy at diagnosis and at completion of MDT: a
      retrospective cohort study of 786 patients in Bangladesh.
AB  - This retrospective cohort study includes all new leprosy patients registered for
      multidrug therapy (MDT) in 1990 at the Danish-Bangladesh Leprosy Mission project
      in Bangladesh. The main objective was to determine the extent of nerve-function
      impairment (NFI) at diagnosis and at completion of MDT, and to identify
      opportunities for intervention and their relative impact on the prevention of
      disabilities (POD). A total of 786 patients were included; 486 males and 300
      females. There were 315 PB, and 471 MB patients. In terms of the WHO leprosy
      disability grading system, at the time of diagnosis 31/315 (9.8%) had grade 1 or
      grade 2 disability in the PB group, and 177/471 (37.6%) in the MB group. The
      incidence rate of NFI during MDT was 3.5 per 100 person years at risk (PYR) in
      the PB group, and 7.5 per 100 PYR in the MB group. In the MB group 37 (7.9%)
      previously normal patients sustained NFI during MDT, whilst 19 (4.0%) with NFI at
      diagnosis showed complete recovery at completion of MDT. The most commonly
      involved nerves were the ulnar (motor function) and the posterior tibial nerves
      (sensibility). Reversal reactions were observed in 0.6% of the PB patients during
      MDT, giving an incidence rate of 1 per 100 PYR. The percentage of MB patients
      diagnosed with reversal during MDT was 14.2%, giving an incidence rate of 6 per
      100 PYR. The percentage of MB patients diagnosed with ENL during MDT was 2.1%,
      with an incidence rate of 1 per 100 PYR. It was concluded that early detection of
      new cases of leprosy would prevent disabilities in more than 30% of all patients,
      thus having the highest impact in the quest for the prevention of disabilities.
      POD activities during and after MDT will prevent disabilities in approximately
      10% of all cases. This study also indicates that treatment with prednisolone is
      effective and should be available at field level for all patients with recent
      NFI.

PMID- 9033201
TI  - Vasomotor reflex testing in leprosy patients, healthy contacts and controls: a
      cross-sectional study in western Nepal.
AB  - OBJECTIVE: To examine test characteristics of laser Doppler vasomotor reflex
      testing for leprosy and to determine the prevalence of abnormal responses in
      leprosy patients, healthy contacts and controls. DESIGN AND PARTICIPANTS: Cross
      sectional study including 89 leprosy patients (mean age 35 years, 74% male), 36
      healthy contacts (29 years, 64% male) and 47 controls (30 years, 68% male), for a
      total of 172 participants. SETTING: Leprosy hospital in an endemic region 200 km
      west of Kathmandu, Nepal. OUTCOME MEASURE: Finger-tip and toe-tip vasomotor
      reflexes elicited by inspiratory gasp were measured using a laser-doppler flow
      temperature technique. Results were expressed in per cent as the maximal
      reduction in bloodflow from baseline. RESULTS: For all 12 measurement sites there
      were highly significant (p > 0.0001 to < 0.004) differences between the three
      groups tested. Leprosy patients consistently had the lowest responses and
      controls the highest, with healthy contacts showing intermediate values.
      Thresholds defined as mean bloodflow reductions among controls minus 1.64 or
      minus 1.96 standard deviations provided optimal combinations of sensitivity and
      specificity. Using these cut-off values around 80% of leprosy patients, 50% of
      healthy contacts and 20% of controls had two or more abnormal reflexes (p <
      0.0001 for differences between groups). CONCLUSIONS: In endemic regions,
      subclinical autonomic neuropathy may be an early but detectable marker for the
      risk of subsequent leprosy, making early treatment and prevention of transmission
      possible. Prospective studies are needed to establish the predictive value of
      abnormal vasomotor reflexes.

PMID- 9033202
TI  - The pattern of cataract and the postoperative outcome of cataract extraction in
      Ethiopian leprosy patients as compared to nonleprosy patients.
AB  - Cataract is a blinding disease occurring all over the world. One of the causes of
      cataract is leprosy. Sixty leprosy and 100 nonleprosy patients were assessed and
      underwent intracapsular cataract extraction. Leprosy patients with cataract were
      much younger than nonleprosy patients. The leprosy group had a significantly
      higher rate of complications and this was seen more in paucibacillary cases.
      There was a higher rate of visual disability in the leprosy group than in the
      nonleprosy group. Cataract was seen in younger patients in the leprosy group.
      This raised the possibility of leprosy being the cause of the cataract. The
      leprosy group consisted mostly of multibacillary cases, however unlike in other
      studies the rate of complications tended to be higher in the paucibacillary
      group. There were no preoperative findings that correlated with a low
      postoperative intraocular pressure.

PMID- 9033203
TI  - Squamous cell carcinoma of the foot arising in chronic ulcers in leprosy
      patients.
AB  - Squamous cell carcinoma (SCC) of the foot is a rare sequelae of chronic
      ulceration secondary to leprosy neuropathy. Most of the tumours are relatively
      slow growing and tend to metastasize late. Survival after local excision is
      generally good. In this series of 17 patients so far there have been 3 deaths
      attributable to SCC, all of whom presented with locally advanced tumours and
      lymph node metastasis.

PMID- 9033204
TI  - Practical problems in the management of leprosy.
AB  - The categorization of leprosy into paucibacillary or multibacillary depends on
      the report of slit-skin smears. Unfortunately, in many control programmes the
      quality of slit smears is below par. Taking the example of India, the main
      reasons were that the work of laboratory technicians was unrewarding as compared
      to serving in a general health care system. There was lack of equipment and an
      unrealistic patient to technician ratio. Future attempts were made by experienced
      workers to devise a clinical system for classifying leprosy as paucibacillary or
      multibacillary based on counting the number of lesions. However this method did
      not prove cost-effective because more paucibacillary patients were classified in
      the multibacillary group increasing the burden of treatment. A renewed attempt to
      improve slit-smear performance should be made by modifying the existing methods.
      This can definitely improve the situation. Patients with multiple macular lesions
      and those with neuritic leprosy are best treated with the MB-MDT regimen. The
      treatment for PB leprosy is to continue up to 6 months but in MB leprosy with a
      high bacterial index a longer duration of MDT may be required. Following
      completion of MDT many cases with deformity are accumulating and their care forms
      are a neglected part of many control programmes. In addition to strengthening the
      infrastructure, simple techniques must be imparted to those with deformities and
      disabilities. This involves the artful and innovative cooperation of the health
      worker, patient and the community. The leprosy worker should be motivated to
      promote such activities.

PMID- 9033205
TI  - Suppression of lymph node lymphoproliferation to viable Mycobacterium leprae by
      peripheral blood-derived monocytes.

PMID- 9033206
TI  - The effectiveness of corticosteroids in the treatment of long-term nerve function
      impairment.

PMID- 9033207
TI  - Comment: divorce among Saudi female leprotic patients: an experience at Ibn Sina
      Hospital.

PMID- 9033208
TI  - [Quality of life in the elderly].

PMID- 9033209
TI  - [International trends in influenza control: preparing for the next pandemic and
      vaccination].
AB  - The prevention of influenza continues to be a major public health concern, and a
      program of vaccination has been promoted, especially to high-risk individuals
      such as the elderly. In addition, concerted efforts are being expended in many
      developed countries in order to better cope with the next influenza pandemic.
      These efforts include enhancing influenza virus surveillance, improving vaccine
      production and its delivery systems, centralizing vaccine distribution and
      establishing priorities, etc. In Japan, on the other hand, influenza is only
      considered a minor illness, and thus little attention has been give to measures
      against influenza. To disseminate information on recent international trends in
      influenza control to Japanese public health specialists, I herein outline the
      recommendations made at two recent international meetings: "Pandemic Influenza:
      Confronting a Reemergent Threat" held in the u.s., at Bethesda, Maryland, in
      December 1995; and "The 7th European Meeting of Influenza and Its Prevention"
      held in Berlin. Germany, in September 1993. Since a routine system capable of
      responding adequately to annual epidemics is considered to be the best defense
      against a pandemic, I also describe the present state of influenza control in
      other countries to contrast it with that in Japan: the target groups for special
      vaccination programs recommended by the U.S. Advisory Committee on Immunization
      Practices; the recommendations for influenza vaccination and reimbursement for
      the vaccination of recommended groups in developed countries: and influenza
      vaccine distribution in Japan and the U.S., 1980-1994. At present in Japan, the
      efficacy of the currently used inactivated vaccine is regarded as either very low
      or none at all. There is also no official national recommendations as to what
      groups should be targeted for active immunization, nor any system for vaccination
      reimbursement. Public health specialists in Japan, therefore need to fully
      understand Japan's peculiar situation and, as a result, better recognize the
      importance of influenza and its prevention.

PMID- 9033211
TI  - [Relationship between medical expenditures and government-sponsored medical check
      ups for the aged].
AB  - Japanese law provides for regular medical examinations for the aged. A simulation
      study to determine the relationship between medical expenditures of
      cardiovascular disease patients and government-sponsored health check-ups for the
      aged was conducted in a small community town in Kanagawa Prefecture. The results
      showed that medical expenditures decreased in accordance with an increase in
      health screening. However, medical expenditure for out-patients increased
      slightly with an increase in screening for those cardiovascular disease patients
      who had not received treatment prior to the government health checkup.

PMID- 9033210
TI  - [Awareness of health and welfare planning for elderly and methods to increase
      awareness: based on social marketing].
AB  - To clarify the socio-psychological factors affecting awareness of health and
      welfare planning for the elderly, a survey of community residents was performed
      in the Tokyo metropolitan area. The results obtained were as follows: 1. There
      were three factors which affected awareness concern about health and welfare
      services for the elderly as a social issue: concern about the local community;
      and concern about the local government. 2. Two other factors which did not affect
      the level of awareness were: anxiety about the health and welfare services for
      the elderly as a personal issue; and having personal experience of nursing care.
      From these results, a method to increase awareness was studied based on social
      marketing methods. Two primary target groups for increasing awareness were
      identified. One target was people who have the socio-psychological factors
      described above. Another target was people who have the potential need for health
      and welfare services but who were not aware of it. That is, they have relatively
      high anxiety about health and welfare services for the elderly as a personal
      issue and have personally experienced nursing care. The method of approach for
      these targets were studied. For the first group, the amount of the information
      available seemed to be important because these persons are ready to recognize the
      need for planning. Therefore, efficient information channels should be selected.
      For the second group, approaches that generate greater consumer participation by
      presenting this as an efficient method for solution of the problem should be
      adopted.

PMID- 9033212
TI  - [Commencement and discontinuance of receiving financial aid for intractable
      disease treatment].
AB  - Data concerning all patients receiving financial aid for 26 types of intractable
      diseases in 1984, 1988 and 1992 were individually linked. Proportions of patients
      who discontinued financial aid in 1988 or 1992 among patients who were receiving
      aid in 1984 (ratio of discontinuance per patients); and ratios of the numbers of
      patients newly commencing aid in 1988 or 1992 to the numbers of patients who were
      receiving aid in 1984 (ratio of commencement per patients) were calculated. The
      results were as follows; 1. Among patients receiving financial aid in 1984,
      ratios of discontinuance per 100 patients were 28 in 1985-88 and 43 in 1985-92.
      Ratios of commencement per 100 patients were 96 in 1985-88 and 203 in 1985-92. 2.
      Ratios of discontinuance and of commencement per 100 patients in 1985-92 among 26
      intractable diseases were 27-96 and 31-1,068, respectively. 3. Ratios of
      discontinuance per patients were higher an age groups 0-19 year and 60 year and
      over than in other age groups. Ratios of commencement per patients were higher in
      age groups 20-29 year and 70 year and over than in other age groups. Both ratios
      were higher among males than among females. 4. Ranges of ratios of discontinuance
      per patients and of ratios of commencement per patients were smaller among 47
      prefectures than among diseases and age groups. The number of patients receiving
      financial aid in 1984 per population among prefectures was inversely correlated
      to ratios of commencement per patients, and were not correlated with ratios of
      discontinuance per patients.

PMID- 9033213
TI  - [An examination of two reporting methods of falls among the elderly living in the
      community].
AB  - This study examined the concordance of two reporting methods for falls (3 month
      and 12 month recall) experienced by elderly living in a rural community. Four
      interview surveys on the occurrence of falls over a 3 month period were conducted
      from 1992 to 1993 every three months. In the final interview, subjects were also
      asked about the occurrence of falls during the past 12 months. A total of 799
      subjects (270 men, 529 women) aged 65 and over, living in a village of Niigata
      Prefecture, responded to all four surveys. The incidence of falls in one year was
      19.0% by the 3 month recall, and 19.1% by the 12 month recall. Overall agreement
      of fall occurrence between the two methods was 98.9%, and a coefficient of kappa
      as a measure of concordance was 0.96. On the other hand, subjects who sustained
      injuries during falls reported in the 3 month reporting did not necessarily
      recall having a fall when interviewed at the end of the study. In any case, this
      study reveals that for surveying falls by the elderly living in the community a 1
      year recall is a reliable method, because of the high agreement of fall
      occurrence when comparing the two methods.

PMID- 9033214
TI  - [Survey for hepatitis in an isolated endemic area].
AB  - Mass health screening for liver disease was conducted in A.H areas in N Town
      which is known to be an endemic area for hepatitis since 1985. Subjects were
      about 1,000 inhabitants in A.H areas and 1795 inhabitants in non-endemic areas
      (control) 6 years or older in age. Informed consent was obtained from all
      inhabitants. All subjects were interviewed for demographic data including age,
      sex, occupation past medical history, surgical operation daily intake of alcohol,
      folk use of remedies such as acupuncture and family history of liver disease.
      Body weight and height were also recorded. Blood obtained from all individuals
      was analyzed for liver function enzyme and hepatitis virus markers including anti
      HCV and HBV markers. Furthermore, health education on how to prevent hepatitis
      and how to treat liver diseases was provided. The results were as follows. 1.
      Overall, the prevalence of anti-HCV was 24.1% in A.H areas, and increased in
      older individuals over 50 years old. To the contrary, it was 2.3% in control
      areas. The prevalence of HBsAg was the same in both areas. 2. Prevalence of
      history of surgical operations, blood transfusion and acupuncture were similar in
      A.H. area sand control area. 3. Risk factors for HCV infection were blood
      transfusion, acupuncture, history of liver diseases and anti-HBs positive. 4.
      Death rate due to liver cirrhosis and hepatocellular carcinoma has been
      increasing year by year during recent years.

PMID- 9033215
TI  - [Supporting roles of health centers in community health practice by
      municipalities].
AB  - Staff of community health centers are expected to support those of municipalities
      so that they can identify health relevant issues in their communities, plan
      strategies to resolve the issues, implement them and evaluate the action. To
      illustrate the role of community health centers, the authors report the process
      of health promotion practice in Taisho-cho, Kochi prefecture, which was supported
      by Kubokawa health center. The health center took the initiative in identifying
      issues in community health through analyzing available information. In a practice
      setting, the health center facilitated involvement and participation by the
      residents and cooperated with other community resources. The process of support
      is discussed from the point of view of community organization practice.

PMID- 9033216
TI  - An important bicentenary.

PMID- 9033217
TI  - Diarrhoeal disease morbidity and home treatment practices in Egypt.
AB  - Diarrhoeal disease is a major cause of death in children in the developing world.
      In developing countries a quarter of infant and childhood mortality is related to
      diarrhoea. The World Health Organization started the Diarrhoeal Disease Control
      Programme (CDD) in 1980 with the objective to decrease diarrhoeal mortality and
      morbidity among young children in developing countries. The aim of this study was
      to measure the prevalence and incidence of diarrhoeal diseases among young
      children and to assess the quality of home case management of diarrhoeal cases.
      Particular emphasis was put on the assessment of drug use during diarrhoea. The
      survey included also the assessment of breast feeding practices. Geographically
      the survey was limited to two governorates, Dakahlia and Gharbia, in lower Egypt,
      which have the largest population (7.12 million) and were thought to be
      representative of lower Egypt. The total sample size was 11032. Seasonally
      adjusted diarrhoea incidence was 3.6 episodes per child under five years of age
      per year. This means a minimum estimate of 30 million cases annually in Egypt.
      Although the majority of the caretakers knew of Oral Rehydration Salts (ORS),
      only 22% of cases with diarrhoea in the last 24 h received ORS. 54% of cases had
      received drugs, and many of the children with diarrhoea received more than one
      drug. The source of drug prescription was most often a private doctor and the use
      of drugs was common among government doctors and health workers. The high
      proportion of cases treated with drugs, other than ORS, is the major problem in
      diarrhoeal home case management in Egypt. The message of ORS has penetrated into
      the general population well, but the practices of health professionals have not
      changed. To improve the situation further, training of health workers in correct
      case management is needed. Paediatric forms of symptomatic antidiarrhoeal drugs
      should also be withdrawn from the market.

PMID- 9033218
TI  - Enterotoxigenic Escherichia coli (ETEC) in hospitalised Arab infants from Judea
      area--west bank, Israel.
AB  - Enterotoxigenic Escherichia coli and other related enterotoxigenic species were
      isolated from 176 (44%) of 399 infants hospitalised in 'Caritas Baby Hospital' in
      Bethlehem, during April-December 1993. Ninety four of the patients infected by
      ETEC, were clinically evaluated. Most of them suffered from diarrhoea, quite
      often with fever and vomiting. Dehydration occurred in 58.3% of the patients and
      failure to thrive (FTT) in 28.5% of them. Severe illness resulted in marasmus in
      five patients and in the death of two others. Most of the ETEC strains (84%) were
      of ST toxin type. Correlation was found between the degree of toxigenity and the
      severity of the gastroenteritis. The most prevalent ETEC "O' serogroups were 0-6,
      0-20, 0-8, 0-86, 0-126, 0-128 and 0167. Colonization Factors Antigens (CFAs) were
      identified in 36% of the isolates, CFAI was characteristic of group 0-126 and 0
      128. In the principal O-groups there were high percentages of sensitivity to the
      antibiotics ceftriaxone, nalidixic-acid, gentamicin and norfloxacin, with
      resistance to anoxycillin, tetracycline and cotrimoxazole.

PMID- 9033219
TI  - Immunity to tetanus in the 3-20 year age group in Italy.
AB  - In Italy, systematic mandatory tetanus immunization of children started in 1968.
      In 1989, immunity against tetanus was assessed in a random sample of 758 healthy
      subjects aged 3-20 y, from four Italian cities. There were 257 subjects 3-5 y old
      all residing in Southern Italy and 501 subjects 11-20 y old from both the South
      and North. The overall prevalence of non-immune subjects was 19.1%, without
      difference by sex. The rates of subjects lacking protective antibody titres was
      25.3% in children 3-5 y old (all coming from South and the islands), 11.5% in
      those 11 y old, and 18.9% in the 18-20 y age-group, respectively. Subjects 11-20
      y old residing in the South and the islands were more likely to be non-immune
      that those residing in the North (20.2% vs 6.0%; P < 0.01). Socio-demographic
      indicators such as lowest paternal education and largest family size were both
      unassociated with lack of protective antibodies. These findings indicate that an
      high rate of children in South of Italy do not have protective antibody levels,
      probably as consequence of lack of compliance with the vaccination programme.
      More efforts should be addressed to decrease geographical inequalities in the
      delivery of health care.

PMID- 9033220
TI  - Mothers' attitudes to and experience of pre-school child health services: a
      comparative study in two districts in the west Midlands.
AB  - A postal questionnaire survey was undertaken amongst a ten percent random sample
      of mothers in Walsall and South Warwickshire in order to determine their views
      concerning health services available for their three year old children. A
      response rate of 59% and 75% respectively was obtained. Despite differences in
      demographic profile between the two districts, the overall views of mothers were
      remarkably similar. The majority of mothers were happy with services provided but
      mothers whose first language was other than English were less likely to be
      satisfied. Criticisms included dissatisfaction with waiting times, inappropriate
      timing of clinics, insufficient advice given as well as inconsistencies in advice
      offered. Health visitors in particular were perceived to be helpful and requests
      for further input from them were made. Specific health needs of children from
      ethnic minority backgrounds were discovered which should form the basis of
      further, more detailed local research. The survey also highlighted the high
      prevalence of accidents and asthma among pre-school children.

PMID- 9033221
TI  - Estimation of obesity in schoolchildren by measuring skinfold thickness.
AB  - To determine whether skinfold thickness is correlated with degree of overweight,
      serum levels of cholesterol, and blood pressure in children, 161 boys and 167
      girls aged 9 and 10 y underwent physical examinations at three elementary schools
      in Japan. Triceps skinfold thickness was positively correlated with degree of
      overweight, atherosclerosis index, and systolic blood pressure, and was
      negatively correlated with levels of high-density lipoprotein (HDL) cholesterol.
      Among children who were highly overweight (> or = 30%), those with low triceps
      skinfold thickness (< 11.2 mm) have lower levels of HDL cholesterol, a higher
      atherosclerosis index, and higher systolic blood pressure than those with greater
      triceps skinfold thickness (> or = 11.2 mm). The ratio of degree of overweight to
      triceps skinfold thickness was significantly correlated with levels of HDL
      cholesterol in girls but not in boys. These results suggest that, in overweight
      schoolchildren, skinfold thickness may reflect the risk of future
      hypercholesterolemia and hypertension. Measurement of triceps skinfold thickness
      and determination of degree of overweight may be useful for the estimation of
      obesity in children.

PMID- 9033222
TI  - Cost-effectiveness of dietary treatment of hypercholesterolemia in Spain.
AB  - BACKGROUND: Dietary treatment of hypercholesterolemia is one of the most
      frequently proposed measures to prevent cardiovascular disease. In this study
      cost-effectiveness of dietary treatment in Spain was assessed. METHODS: Cost
      effectiveness ratio was measured in terms of cost per life years gained,
      comparing net programme cost to its effectiveness. Effectiveness was estimated
      using a model that incorporates the Framingham multiple logistic equation to
      obtain the number of coronary events prevented and life years gained according to
      age, sex and initial cholesterol concentration. In this study it was assumed that
      dietary treatment could reduce cholesterol concentration by 5% in the group of
      participants. Net programme cost was estimated as total programme cost less
      averted cardiovascular disease treatment costs due to disease prevention. Costs
      and benefits were estimated for 1990 using a 5% discount rate. RESULTS: Cost per
      life year gained ranged from $6,270 to 61,439 in men and $28,067 to 171,459 in
      women, according to age and initial cholesterol concentration. The lowest cost
      effectiveness ratio was obtained in individuals with a cholesterol concentration
      of 9.7 mmol/l (380 mg/dl) aged 45-49 years in men and 50-54 years in women, and
      the highest one was obtained in those men and women with a cholesterol
      concentration of 5.7 mmol/l (220 mg/dl) aged 60-65 years. Cost per life year
      gained was lower than $25,000 in men aged 35 to 64 years with a cholesterol
      concentration higher than 6.2 mmol/l (240 mg/dl) and it was lower than $35,000 in
      women aged 35 to 64 years with a cholesterol concentration higher than 9.3 mmol/l
      (360 mg/dl). CONCLUSION: Individual dietary treatment of hypercholesterolemia
      could be considered an efficient use of health resources. Programme for dietary
      treatment of hypercholesterolemia should be recommended in men aged 35-64 years
      with hypercholesterolemia (> 6.2 mmol/l) and in women aged 35-64 years with very
      high cholesterol concentrations.

PMID- 9033223
TI  - Unemployment is an important risk factor for suicide in contemporary Sweden: an
      11-year follow-up study of a cross-sectional sample of 37,789 people.
AB  - OBJECTIVE: To evaluate whether unemployment is a risk factor in suicide. DESIGN:
      This study was designed as a follow-up study of a cross-sectional sample. People
      in years at risk were calculated from the date of the interview until death, or
      for those who survived, until the end of the follow-up period at 31 December
      1993. Information on the dependent variable, was obtained from the Cause of Death
      Register by the Swedish personal registration number. The data were analysed by a
      proportional hazard model in order to estimate relative risks (RR) of suicide
      with 95% confidence intervals (CI). The background variables were added one by
      one to the model according to their casual order, namely, sex, age, marital
      status, form of tenure and health status. SETTING: Sweden. SUBJECTS: The present
      study is focused on a simple random cross-sectional sample of 37789 people aged
      20-64 y. The data is collected only once from each person. MAIN OUTCOME MEASURES:
      Suicide and undetermined deaths (E950-959 and E980-989 according to ICD-8 and ICD
      9 1987). RESULTS: The high relative risk for suicide for unemployment/sickness
      pension decreased from 3.86 to 1.93 (1.63-3.67) when adding the variables sex,
      age, marital status, form of tenure and health status one by one into the model.
      People living alone, form of tenure (renting an apartment) and those who reported
      poor health had high suicide risks in the final model varied between 1.66 and
      3.39. CONCLUSIONS: Unemployment is an important social variable associated with
      increased suicide risk. Socio-economic position defined as form of tenure is
      important for social patterning in suicide. Self-rated poor health is also
      strongly related to suicide.

PMID- 9033224
TI  - Travel times and radiotherapy uptake in two English counties.
AB  - OBJECTIVES: To examine whether longer travel times for radiotherapy are
      associated with reduced overall uptake of radiotherapy treatment, or with reduced
      uptake of palliative as opposed to radical radiotherapy. DESIGN: Correlations of
      weighted average travel times for radiotherapy with overall radiotherapy uptake,
      and of travel times to one cancer centre with the ratio of palliative to radical
      radiotherapy at that centre. SETTING: The fourteen local authority (county)
      Districts of Bedfordshire and Hertfordshire. SUBJECTS: Residents of Bedfordshire
      and Hertfordshire registered by the Cancer Registries as attending hospital with
      a diagnosis of cancer, and registered as receiving radiotherapy treatment.
      Residents recorded by single cancer centre as receiving radical or palliative
      radiotherapy at that centre. RESULTS: There was no significant correlation
      between travel times for treatment and overall radiotherapy uptake (r = 0.40, P =
      0.18), or with the ratio of palliative to radical radiotherapy at a single centre
      (r = -0.29, P = 0.34). Both measures of uptake showed considerable variability.
      Longest travel times were about one hour. CONCLUSIONS: Travel times up to one
      hour do not appear to reduce radiotherapy uptake, and the variability observed is
      likely to be due to other factors. The recommendation of the Chief Medical
      Officer's expert advisory group on cancers, that radiotherapy should be provided
      in larger cancer centres, is unlikely to result in lower radiotherapy uptake with
      travel times of this order.

PMID- 9033225
TI  - Seasonal variation and weather effects on road traffic accidents in Riyadh city.
AB  - The monthly variation of Road Traffic Accidents (RTAs) in Riyadh city in the
      period 1989-1993 has been studied with reference to time of day, lighting
      conditions and prevalent weather conditions. Total RTA accidents were
      significantly more common, being directly correlated, with increased dry and wet
      bulb temperatures and significantly less common, being inversely correlated, with
      increased relative humidity and amount of precipitation of rain, snow, hail etc.
      However, RTAs recorded on rainy days only were significantly more common and
      directly correlated with precipitation (Note days of snow and hail are very rare
      in Riyadh city). Seasonal variation in RTAs was evident being maximal during the
      summer season particularly between 12 noon and 3 pm. This period is characterized
      by heavy traffic and intense sunlight. The role of hot weather prevalent in Saudi
      Arabia, where average temperatures of 34.4-34.7 degrees C with maximum of 40-42.7
      degrees C are common in summer, have been suggested to be an important factor
      leading to increased stress and decreased performance of intellectual tasks which
      require considerable physical effort and motor skills. Increased heart rates,
      exacerbation of existing pathologic conditions such as heart disease and
      emphysema and loss of visual acuity have been reported. Consequently, prolonged
      exposure to heat must be considered as a hazard to the safety and health of
      drivers and a factor leading to an increased incidence of RTAs.

PMID- 9033226
TI  - AIDS--1996.

PMID- 9033227
TI  - Ethical analysis of a case of ectopia cordis.

PMID- 9033228
TI  - Zidovudine and interferon therapy for adult T-cell leukaemia/lymphoma. Results of
      a preliminary study at UHWI-Mona.
AB  - Seven patients with adult T-cell leukaemia/lymphoma (ATL) were treated with a
      combination of zidovudine (AZT) and interferon after failed chemotherapy. One
      patient showed a major response for nine months. The remainder showed progressive
      disease further complicated by drug toxicity. The poor responses could be
      explained by patient selection, since most patients had advanced disease
      refractory to chemotherapy. A larger more protracted study is required for
      further evaluation of this treatment option.

PMID- 9033230
TI  - Maternal deaths associated with caesarean section.
AB  - Twelve Caesarean section-associated maternal deaths were encountered over a 15
      year period. The major operative risk factors were pregnancy-induced
      hypertension, obesity and general anaesthesia. Severe preeclampsia was the
      forerunner to postoperative cardiac failure, consumptive coagulopathy and
      difficult airway manipulation. We conclude that pregnancy-induced hypertension
      and its ramifications pose the greatest threat to maternal survival from a
      Caesarean section.

PMID- 9033229
TI  - A prospective study of ward referrals for renal disease at a Jamaican and a
      United Kingdom hospital.
AB  - Seventy ward referrals for renal disease were prospectively studied at each of
      two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston,
      Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral
      population was significantly younger, 89% being less than 60 years of age
      compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF)
      at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis
      (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy.
      Primary renal disease and diabetes mellitus were the major causes of end-stage
      renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI
      and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome
      occurred more frequently at UHWI than at NCH but the numbers were small (p <
      0.05). Mortality rates were similar among patients with ARF and nephrotic
      syndrome at both centres, but were higher for patients with chronic renal failure
      (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis
      (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on
      haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD
      were not offered maintenance dialysis because of inadequate facilities. The major
      difference in management and outcome between the two centres occurred in cases
      with CRF, suggesting that survival in patients with CRF in Jamaica could be
      improved if this therapeutic modality was available.

PMID- 9033231
TI  - Recurrence of endogenous cortisol secretion after bilateral total adrenalectomy-
      2 cases.
AB  - Bilateral total adrenalectomy is a common treatment for Cushing's Syndrome in
      underdeveloped countries where limited resources restrict the use of extensive
      investigations, where the source of ACTH secretion is not identified or where
      neurosurgical facilities are minimal. Two cases of recurrence of cortisol
      secretion managed at the University Hospital of the West Indies are presented.
      The aetiology is discussed.

PMID- 9033232
TI  - Primary leiomyosarcoma of bone.
AB  - Primary leiomyosarcoma of bone is rare. We present the clinicopathological
      features of a case, the first documented from the Caribbean, seen recently at our
      institution.

PMID- 9033233
TI  - Thyroid papillary carcinoma arising in a branchial cleft cyst.
AB  - We describe the clinico-pathological features and discuss the possible
      pathogenetic mechanism of thyroid papillary carcinoma arising in a branchial
      cleft cyst. This has been described only once previously in the literature.

PMID- 9033234
TI  - Compartment syndrome due to reperfusion injury.
AB  - Theoretically, tissue oedema due to reperfusion injury may be severe enough to
      cause compartment syndrome. One such rare case is presented.

PMID- 9033235
TI  - Ramsay Hunt syndrome complicated by contralateral cerebral infarction.
AB  - Varicella-zoster virus has been associated with a variety of neurological
      manifestations. We describe a patient with the Ramsay Hunt Syndrome who developed
      a contralateral cerebral infarction.

PMID- 9033236
TI  - Solar radiation and human health.

PMID- 9033237
TI  - HF acid ionization in water: the first step.
AB  - The results of a theoretical study of the first acid-ionization step to produce a
      contact-ion pair are presented for HF in water. The reaction is found to be an
      adiabatic quantum proton transfer, and has an activation barrier in a collective
      solvent reaction coordinate of ca. 3 kcal mol-1.

PMID- 9033238
TI  - Scientific basis for the content of routine antenatal care. I. Philosophy, recent
      studies, and power to eliminate or alleviate adverse maternal outcomes.
AB  - BACKGROUND: Scope and content of antenatal care programs are ritualistic rather
      than evidence-based. We wanted to identify elements of antenatal care which are
      of proven benefit in preventing or ameliorating specific adverse outcomes in the
      mother: bleeding, anemia, preeclampsia, sepsis and genito-urinary infection and
      obstructed labor. METHODS: Review of recent literature, especially randomized
      controlled trials. RESULTS AND CONCLUSIONS: Recent trials indicate that fewer
      routine visits for low-risk women do not put pregnancies at increased risk but
      may lessen patient satisfaction. Bleeding in pregnancy has many causes, none of
      which can be eliminated through antenatal care. Risk factors can be identified by
      history-taking. Counselling and advice on what to do is the best option. Anemia
      in pregnancy is common, especially in developing countries. Routine iron
      supplementation is not necessary in well-nourished populations, but iron and
      folate should be provided for every pregnant woman in areas of high anemia
      prevalence; based on circumstantial evidence. Hemoglobin (Hb) determination as a
      routine test is more important late (around week 30) than early in pregnancy:
      high Hb is a danger signal. It is uncertain whether early detection of pre
      eclampsia will reduce the incidence of eclampsia. Recent trials do not support
      routine aspirin to prevent pre-eclampsia among low risk women, nor is there
      evidence that anti-hypertensive treatment of mild pre-eclampsia will prevent more
      severe disease, but improved detection and care may still lead to better outcome.
      As to infections, urine culture and dipstick for leucocyte esterase and nitrite
      with subsequent treatment of positive cases will reduce the risk of
      pyelonephritis and appears to be cost-effective. Serological screening and
      treatment of syphilis is inexpensive and cost-effective. Obstructed labor can be
      anticipated in multiparas based on obstetrical history. Hospital delivery should
      be secured. Height of nulliparas should be recorded where hospital birth is not
      routine and a discriminatory level for hospital delivery decided locally.
      External version of breech lie does reduce the incidence of breech births and
      cesarean delivery.

PMID- 9033239
TI  - Scientific basis for the content of routine antenatal care. II. Power to
      eliminate or alleviate adverse newborn outcomes; some special conditions and
      examinations.
AB  - BACKGROUND: There is uncertainty concerning antenatal care as a tool to eliminate
      or alleviate adverse outcomes in the newborn. We identified congenital
      conditions, intrauterine infections, intrauterine growth retardation, preterm
      birth and some specific infectious diseases in the mother with a view to
      prophylactic and other interventions. The value of some special diagnostic tools
      is also under discussion. METHODS: Review of recent literature, especially
      randomized controlled trials and systematic reviews. RESULTS AND CONCLUSIONS:
      Genetic abnormalities cannot be prevented after conception, but many of them, and
      a number of acquired conditions, can be discovered by ultrasonographic and
      biochemical diagnostics. The advisability of screening must be determined locally
      for each condition, based on prevalence, treatment options and the legal
      requirements for abortion. Smoking, excessive alcohol intake, and severe
      undernutrition cause fetal growth retardation. Interventions to reduce maternal
      smoking have had limited success. Protein-energy supplementation only modestly
      affects birthweight. Routine measurement of uterine height is a good predictor of
      severe growth retardation and in rural settings of perinatal death. Preterm birth
      has been linked to ascending infection and subsequent rupture of the membranes.
      Attempts to eradicate local infections have shown some benefit but results are
      not convincing yet. Cervical cerclage and betamimetic drugs have little, if any,
      effect. Claims for reduction of physical strain (standing > 5 hours) at work
      should be supported. Tuberculosis in the mother should be discovered and treated.
      Malaria prophylaxis during pregnancy will protect the mother and possibly benefit
      the fetus. Adequate tetanus immunization of all mothers is a high priority
      intervention in developing countries. In HIV-positive mothers, Zidovudine ante-
      and perinatally will lower perinatal HIV-transmission significantly. Risk scoring
      may help identify some women for referral to higher level of care. Routine
      ultrasonography does not improve the outcome of pregnancy in terms of live births
      and morbidity, but may influence mortality through discovery and abortion of
      fetuses with major malformations. One vaginal examination during pregnancy is
      recommended but no repeat procedure unless medically indicated.

PMID- 9033240
TI  - Ability of intrauterine bacterial lipopolysaccharide to cause in situ uterine
      contractions in pregnant rabbits.
AB  - BACKGROUND: To investigate the ability of bacterial lipopolysaccharide delivered
      by the intra-uterine route to cause uterine contractions in rabbits, and to
      assess the suppressive effect of urinary trypsin inhibitor on them. METHODS: Both
      pregnant and non-pregnant rabbits were chronically implanted with a force
      transducer to make it possible to record isometric uterine contractions under
      unanesthetized and unrestrained conditions. Lipopolysaccharide (10
      micrograms/animal) was administered via a catheter to their uteri; and then,
      after confirmation of lipopolysaccharide-induced uterine contractions, urinary
      trypsin inhibitor (3,000 or 10,000 units/animal/time) or saline solution was
      injected through the catheter, 5 times for pregnant animals or 3 times for non
      pregnant animals at 1-hour intervals in both cases. Their uterine contractions
      were continuously recorded for 3 to 5 hours. Effects of lipopolysaccharide (10
      micrograms/ml) and urinary trypsin inhibitor (100 and 1,000 units/ml) on the
      contraction of isolated uteri from pregnant mice were also measured, as was their
      production of prostaglandin E2 and prostaglandin F2 alpha by an enzyme
      immunoassay method. RESULTS: Lipopolysaccharide augmented the in situ uterine
      contractions in both pregnant and non-pregnant rabbits, as well as the in vitro
      contractions of isolated uteri from pregnant mice. Lipopolysaccharide also
      increased the uterine prostaglandin production. Urinary trypsin inhibitor
      inhibited significantly the lipopolysaccharide-induced uterine contractions and
      the prostaglandin production. CONCLUSIONS: Lipopolysaccharide enhanced uterine
      contractions through, at least partly, a direct mechanism via uterine
      prostaglandin production, which action could explain the onset of preterm
      delivery due to intrauterine bacterial infection. As urinary trypsin inhibitor
      suppressed the lipopolysaccharide-induced uterine contractions, this inhibitor
      may be a hopeful candidate of a drug for prevention of preterm delivery.

PMID- 9033241
TI  - Fetal breathing recorded by actocardiogram and real--time ultrasonography. A
      comparison.
AB  - BACKGROUND: The aim of the study is to evaluate the ability of fetal
      actocardiogram to assess fetal breathing movements. METHODS: A descriptive study.
      Evaluation of the agreement between real-time ultrasound and actocardiographic
      assessment of fetal breathing movements. Eleven unselected pregnancies admitted
      because of various pregnancy complications. RESULTS: In six cases the breathing
      pattern recorded by the actocardiogram correlated to the findings with real-time
      ultrasonography. In five cases where fetal breathing was observed on the
      ultrasound screen, the actocardiogram did not either indicate breathing or was of
      an indecisive appearance. Two cases where no breathing was observed on real-time
      ultrasound yielded actocardiograms without patterns typical of breathing, but
      with activity difficult to distinguish from breathing. CONCLUSIONS: With the
      paper speed set at 3 cm/min it is possible to detect some types of fetal
      breathing or the absence of breathing with accuracy on the actocardiogram.
      However, in cases without deep and regular diaphragmatic excursions it is not
      possible to evaluate breathing with certainty by the actocardiogram.

PMID- 9033242
TI  - Marine n-3 fatty acid and calcium intake in relation to pregnancy induced
      hypertension, intrauterine growth retardation, and preterm delivery. A case
      control study.
AB  - OBJECTIVE: To evaluate whether low intakes in pregnancy of marine n-3 fatty acids
      or calcium increase the risk of preeclampsia, pregnancy induced hypertension,
      intrauterine growth retardation, or preterm delivery and whether high intakes of
      the above nutrients increase the risk of postterm delivery. DESIGN: A case
      control nested in cohort study. SUBJECTS AND METHODS: Between 1989 and 1991 a
      cohort of 9,434 pregnant women was established. Forty-three preeclamptics, 179
      women with pregnancy induced hypertension, 182 with intrauterine growth
      retardation, 153 delivering preterm, and 189 delivering postterm together with
      256 controls were sampled for this study. Dietary information was obtained
      retrospectively between six months and 3 1/2 years after delivery using a
      semiquantitative food frequency questionnaire, whilst information on potential
      confounders was obtained from the cohort data base and analyzed by multiple
      logistic regression. Questions regarding marine n-3 fatty acids and calcium
      intake provided the basis for categorization into three and five intake groups
      respectively. RESULTS: For all five pregnancy outcomes and both nutritional
      factors, none of the confounder-adjusted odds ratios comparing higher intake
      levels with the lowest intake level were significant. Neither were chi 2-tests
      for trend calculated for each pregnancy outcome statistically significant (p >
      0.20). Odds ratios for highest versus lowest intake levels were for n-3 fatty
      acids 0.79 ((0.27 to 2.34 (95% CI)) for pregnancy induced hypertension, 1.00
      (0.34 to 2.95) for intrauterine growth retardation, and 0.99 (0.35 to 2.74) for
      preterm delivery; for calcium they were 0.92 (0.33 to 2.60) for pregnancy induced
      hypertension, 0.77 (0.25 to 2.42) for intrauterine growth retardation, and 1.05
      (0.36 to 3.10) for preterm delivery. CONCLUSIONS: No associations could be
      detected in these data between calcium or fish intake and adverse pregnancy
      outcome.

PMID- 9033243
TI  - Obstetric outcome of natural and assisted conception twin pregnancies is similar.
AB  - BACKGROUND: The risk of obstetric intervention and adverse fetal or neonatal
      outcome is considerably higher in multiple gestation than in singleton pregnancy.
      How assisted conception influences obstetric management and outcome in twin
      pregnancies has not been evaluated. METHODS: A survey of all twin pregnancies in
      Iceland and the Tayside Region, Scotland for a four year period, 1990-93,
      comparing twins after assisted fertilization with natural conception. RESULTS:
      The total number of twin pregnancies was 522, of which 453 were natural
      conceptions and 69 assisted. The twin rate was 1:75 among natural conceptions,
      but 1:5 in women having assisted fertilization. Mean gestational age in both
      groups was 36 weeks. Elective Cesarean section was used more often in the
      assisted conception group (odds ratio 2.57; p = 0.003). Induction rates did not
      differ to any significant degree and once labor commenced, no difference was seen
      between assisted and natural conception twins in the mode of delivery or neonatal
      short term morbidity. Birthweight, gestational length and perinatal mortality
      rates by conventional and extended classification were not different. CONCLUSION:
      After allowing for more frequent elective Cesarean section in the obstetric care
      of the assisted conception pregnancies, there was no major difference in
      obstetric and neonatal management or outcome between twins resulting from natural
      and assisted conception.

PMID- 9033244
TI  - Effective obstetric paracervical block with reduced dose of bupivacaine. A
      prospective randomized double-blind study comparing 25 mg (0.25%) and 12.5 mg
      (0.125%) of bupivacaine.
AB  - BACKGROUND: To study whether paracervical block (PCB) with 12.5 mg (0.125%) of
      bupivacaine is as effective as with 25 mg (0.25%) and if there are differences in
      fetal heart rate (FHR) patterns between the doses. METHODS: A prospective,
      randomized double-blind study. Fifty-two patients received PCB with 25 mg and 45
      patients with 12.5 mg of bupivacaine. Pain intensity was assessed by the patients
      on a horizontal visual analog scale (VAS). Fetal heart rates of the fetuses were
      analyzed visually concerning basal rate, variability, accelerations, bradycardia,
      silent pattern and decelerations. RESULTS: The pain relief was statistically
      significant in both groups up to 120 min after PCB. The VAS-values were similar
      in both groups both before and after PCB. Fetal heart rate changes appeared in
      both groups more frequently after than prior to PCB. In patients receiving 25 mg
      of bupivacaine there appeared to be more FHR changes than in those receiving 12.5
      mg. CONCLUSIONS: Paracervical block with 12.5 mg of bupivacaine is an effective
      method to relieve pain during labor. Fetal heart rate changes seemed to appear
      less frequently with this reduced dose. It seems that by lowering the dose of
      bupivacaine it is possible to reduce fetal side-effects without losing analgesic
      effect.

PMID- 9033245
TI  - Maternal serum levels of interleukin-6 and clinical characteristics of normal
      delivery at term.
AB  - BACKGROUND: The objective of the present study was to study participation of
      cytokines and cytokine inhibitors during the process of normal parturition, as
      assessed by maternal serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6),
      tumor necrosis factor (TNF) and soluble tumor necrosis factor receptors (sTNFRs,
      p55 and p75). MATERIALS AND METHODS: Twenty-six healthy women in normal term
      labor were observed during parturition and until 2 h post partum. Serum was
      sampled every 2 h, and an evaluation of strength and frequency of contractions
      was performed at the time of sampling. Concentrations of IL-1, IL-6, TNF, p55 and
      p75 were analyzed, and non-parametric tests were used to study whether any
      relationship existed between the serum analyzes and the clinical characteristics
      of parturition. RESULTS: There was a significant association between the strength
      of contractions and the levels of IL-6 and p55. In addition, IL-6 concentrations
      and frequency of contractions were correlated. Maternal serum levels of IL-6 and
      p55 were highest 2 h post partum. TNF activity was detected in samples from nine
      women, whereas IL-1 was not found in any sample. CONCLUSIONS: The present study
      suggests a role of IL-6 and p55 in normal labor. However, as women being studied
      already were in labor, the study does not allow any conclusions whether observed
      changes in IL-6 and p55 levels have a causal relation to the process of labor or
      if changes are secondary effects of the process itself.

PMID- 9033246
TI  - Factors influencing the reliability of oral contraceptives.
AB  - BACKGROUND: The reliability of oral contraceptives (OC) is high but several known
      factors can potentially induce failures. The dose of estrogen (EE) has been
      reduced through the years. Interaction with concomitant use of other medicine is
      wellknown and gastroenteritis can reduce the uptake of EE. To further
      characterize and quantify these factors we have performed this study. METHODS:
      Among patients admitted for legal abortion we selected those who had taken OC
      (only combined preparations; gestagen-only preparations were excluded) according
      to the prescription but nevertheless became pregnant. Various parameters were
      noted. RESULTS: Among 8058 women 70 women were found. Twenty-nine used three
      phased and 25 used low-dose OC while the rest used high-dose, two-phased or
      unknown OC (four, five and seven patients respectively). Five patients used other
      medicine concurrently (salbutamol, astemizol, mianserin, chlorcyclizin, paradryl,
      carbamazepin, lithium, chlorprotoxin and imipramin). Sixteen patients had
      symptoms of gastroenteritis at the time of conception. Forty-nine patients had
      failure without any known influencing factors. There was no significant
      difference between the various OC used by the patients compared to sales of them
      in Denmark. About two-thirds of the patients wanted to continue with OC as future
      prevention. CONCLUSIONS: Failure of OC is a rare event but can occur in case of
      concurrent gastroenteritis or use of other medicine but in many cases, however,
      no definite cause can be determined. The EE-content of the various OC was not
      found to have any influence. Although OC-failure had occurred two-thirds of the
      patients wanted to continue the use of OC.

PMID- 9033249
TI  - A population study of urinary incontinence and nocturia among women aged 20-59
      years. Prevalence, well-being and wish for treatment.
AB  - BACKGROUND: The aim was to study urinary incontinence (UI) and nocturia in a
      female population; prevalence, effect on well-being, wish for treatment and
      result of treatment in primary health care. METHODS: A postal questionnaire was
      sent to all women aged 20-59 years who were scheduled for gynecological health
      examination by midwives in a primary health care district during one year.
      Questions concerning well-being were based on the Gothenburg QOL instrument. All
      women with incontinence were offered treatment by a midwife and a family doctor.
      RESULTS: Of the included 641 women, 491 (77%) answered the questionnaire. The
      prevalence of urinary incontinence was 27.7%, 3.5% having daily leakage. Nocturia
      occurred in 32 women (6.5%), 12 of whom were also incontinent. Self-assessed
      health, sleep, fitness and satisfaction with work situation decreased
      significantly with increased frequency of incontinence. Well-being was not
      correlated to type of incontinence. Nocturia correlated to poor health and sleep.
      About a quarter of the incontinent women started treatment when offered and 80%
      of those who completed the treatment program were subjectively improved. Wish for
      treatment was directly correlated to frequency of incontinence but not to type.
      CONCLUSIONS: Urinary incontinence and nocturia affect well-being in a negative
      way. Well-being and wish for treatment correlate to frequency of incontinence but
      not to type of incontinence. Most women with UI accept it, only about a quarter
      of incontinent women, or 6-7% of all women in the studied age group, want
      treatment. Treatment of female urinary incontinence in primary health care is
      successful.

PMID- 9033247
TI  - Is dilatation and curettage obsolete for diagnosing intrauterine disorders in
      premenopausal patients with persistent abnormal uterine bleeding?
AB  - BACKGROUND: To determine the predictive value of dilatation and curettage (D&C)
      for diagnosing intrauterine disorders in patients with persistent abnormal
      uterine bleeding. METHODS: An observational descriptive study was performed in a
      large university-affiliated teaching hospital. The suspicion of intrauterine
      disorders described in theater-reports involving D&C was compared with the
      hysteroscopical findings in 131 premenopausal patients with persistent complaints
      of abnormal uterine bleeding who were referred by other gynecologists within six
      months after D&C. Pre-test probability (prevalence), post-test probabilities
      (predictive values) and likelihood-ratio's were calculated. RESULTS: The pre-test
      probability for all intrauterine disorders was 0.49. The post-test probabilities
      for a 'suspect' and a 'not suspect' D&C were 0.61 and 0.46 respectively with an
      overlap of confidence-intervals. The corresponding likelihood-ratio's were 1.69
      and 0.87 respectively. CONCLUSIONS: D&C findings were of no value in the
      prediction of the presence or absence of intrauterine disorders in this
      population with persistent complaints.

PMID- 9033248
TI  - Cytobrush and endocervical curettage in the diagnosis of dysplasia and malignancy
      of the uterine cervix.
AB  - BACKGROUND: The validity of cytobrush and endocervical curettage combined with
      colposcopically directed biopsies in the diagnosis of cervical dysplasia and
      malignancy has not been evaluated in randomized trials. We aimed to elucidate the
      diagnostic validity of the two methods. METHODS: A prospective, randomized study
      of 180 consecutive patients. All patients were examined without anesthesia by
      colposcopically directed biopsies of the ectocervix and randomly assigned to
      either cytobrush or endocervical curettage. Patients with < or = CIN 1 were
      investigated with the alternative method three months later. Patients with > or =
      CIN 2 had a cone biopsy. RESULTS: One hundred and thirty-one patients were
      evaluable. The sensitivity of cytobrush and endocervical curettage combined with
      colposcopically directed biopsies of the ectocervix was 96% and 84% (p = 0.08),
      respectively. The specificities of the two investigations were 95% and 88%,
      respectively (p = 0.78). All cytobrush specimens were evaluable but because of a
      low recovery of endocervical material a diagnosis could not be made in 12% of the
      patients examined by endocervical curettage. CONCLUSION: The sensitivity of the
      combined use of cytobrush and biopsies of the ectocervix was equal to or higher
      than the sensitivity of endocervical curettage and ectocervical biopsies. The
      specificities of the two investigations were much alike. All cytobrush specimens
      were evaluable but a diagnosis could not be performed in 12% of the endocervical
      curettage specimens because of too little endocervical material. Furthermore,
      cytobrush is less inconvenient to the patient. Therefore, in the follow-up of
      patients with cervical dysplasia endocervical curettage may be replaced with
      cytobrush.

PMID- 9033250
TI  - Spontaneous pregnancy in patients with premature ovarian failure.

PMID- 9033251
TI  - Adnexal torsion in pregnancy.

PMID- 9033252
TI  - High incidence of histologic chorioamnionitis in women with gestational vaginal
      bleeding.

PMID- 9033253
TI  - The structural basis of molecular genetic deletions. An integration of classical
      cytogenetic and molecular analyses in pancreatic adenocarcinoma.
AB  - Molecular genetic alterations are known to be important in human carcinoma, but
      the structural basis of these changes is largely unknown. To examine the basis of
      these changes, we compared the karyotypic chromosomal abnormalities of primary
      pancreatic adenocarcinomas with the molecular changes identified in these same
      cancers. In 14 cancers with abnormal karyotypes, 65% (123 of 188) of the
      chromosomal arms with molecular loss of heterozygosity (LOH) were associated with
      karyotypic structural anomalies. Karyotypic changes accounting for these
      molecular allelic losses included 83 chromosome losses, 18 partial deletions,
      nine isochromosomes, eight additions, and five translocations. Eight bomozygous
      deletions were also identified by molecular analyses. Of the three homozygous
      deletions identified at 9p21, the only karyotypic change was a single case in
      which one entire copy of chromosome 9 was deleted. Of the four homozygous
      deletions identified at 18q21.1, one showed a loss of both copies of chromosome
      18, two showed a loss of one copy of chromosome 18, and the fourth had two
      structurally normal copies of chromosome 18. One homozygous deletion was
      identified at 13q12.3, and the karyotype revealed the loss of one entire copy of
      chromosome 13. The second copy of chromosome 13 in this carcinoma was
      structurally normal. These results indicate that chromosomal structural anomalies
      can account for two-thirds of the LOH in pancreatic adenocarcinomas and that most
      homozygous deletions are likely to be interstitial chromosomal deletions that are
      below the detection limit of conventional karyotypic analyses. Some of the
      molecular deletions detected as LOH on chromosomes with karyotypically normal
      structure can be explained by chromosomal loss with reduplication of the
      remaining chromosome.

PMID- 9033254
TI  - Differential retinoblastoma protein expression in neuroendocrine tumors of the
      lung. Potential diagnostic implications.
AB  - Neuroendocrine lung tumors have been considered by some to be a continuum ranging
      from relatively benign typical carcinoids to highly malignant small-cell
      carcinomas. Histopathological diagnosis may sometimes be difficult because of
      their overlapping features. Correct classification, however, carries important
      prognostic and therapeutic significance. To determine the clinicopathological
      implications of retinoblastoma (RB) protein expression in these neoplasms, we
      examined the RB status in a series of neuroendocrine tumors by
      immunohistochemical analysis of paraffin-embedded tissue sections. A total of 105
      tumors were studied. All 44 typical and 15 atypical carcinoids, one of which was
      initially misdiagnosed as a small-cell carcinoma, manifested a heterogeneous RB
      positive staining pattern. Atypical carcinoids in general showed an increase in
      the number of tumor cells with strong nuclear staining compared to typical
      carcinoids. In contrast, all 40 small-cell and 6 large-cell neuroendocrine
      carcinomas failed to show RB staining in any tumor nuclei, indicating loss of RB
      function. Our results suggest that RB status as measured by immunohistochemical
      staining can be used as a marker to distinguish typical and atypical carcinoids
      from small-cell and large-cell neuroendocrine carcinomas.

PMID- 9033256
TI  - Correlation of high lactate levels in head and neck tumors with incidence of
      metastasis.
AB  - Using quantitative bioluminescence imaging, tissue concentrations of ATP,
      glucose, and lactate were registered in biopsies that were taken from primary
      tumors of human head and neck at the time of first cancer diagnosis. From 15
      patients investigated at present, 6 had locoregional lymph node metastasis, 6 had
      no detectable metastatic spread, 2 biopsies contained dysplasias, and 1 biopsy
      consisted exclusively of normal mucosal and submucosal tissue. There was no
      correlation between staging or grading and any of the metabolic parameters
      measured. Mean lactate concentrations (+/-SD) were significantly higher and
      scattered over a wider range in tumors with metastatic spread (12.3 +/- 3.3
      mumol/g) in comparison with malignancies in patients without metastasis (4.7 +/-
      1.5 mumol/g). Despite the low number of patients, these differences were
      statistically highly significant (P < 0.005; Mann-Whitney). Neither ATP nor
      glucose contents showed such a correlation with the emergence of metastasis. Mean
      lactate contents of the two dysplasias were 0.1 and 3.5 mumol/g; that of the
      normal tissue was 0.1 mumol/g. Although these findings have to be verified in a
      higher number of patients, the present data indicate that elevated lactate levels
      in primary tumors of head and neck may be associated with a high risk of
      metastatic spread. With the underlying mechanisms remaining to the investigated,
      lactate imaging is possibly useful as an early indicator of the malignant
      potential of tumors in patients.

PMID- 9033255
TI  - Aberrant p27kip1 expression in endocrine and other tumors.
AB  - The p27kip1 (p27) gene encodes an inhibitor of cyclin-dependent kinase activity.
      The expression of p27 protein in normal and neoplastic tissues was investigated
      by immunoblotting and immunohistochemistry. Immunoblotting studies detected a 27
      kd protein band that was decreased in neoplastic pituitary tissues compared with
      normal pituitary. Immunostaining of 177 tissues showed abundant expression of p27
      protein in normal tissues with decreased numbers of immunoreactive cells in
      adenomas and carcinomas in both endocrine and nonendocrine tissues. p27
      expression was inversely related to the proliferation marker Ki-67 antigen
      detected with monoclonal antibody MIB-1. Parathyroid adenomas and hyperplasias
      had similar Ki-67 labeling indices; however, hyperplasias had threefold more p27
      positive cells than parathyroid adenomas, suggesting that p27 immunostaining may
      be useful in distinguishing between these two conditions. These results indicate
      that there is widespread aberrant p27 expression in hyperplastic tissues and in
      benign and malignant neoplasms compared with normal tissues. Immunohistochemical
      analysis of p27 along with Ki-67 may be used to assess the biological behavior of
      various neoplasms, to classify hyperplastic and neoplastic tissues, and to study
      cell cycle regulation during tumor progression.

PMID- 9033257
TI  - Beta-amyloid protein-containing inclusions in skeletal muscle of apolipoprotein-E
      deficient mice.
AB  - The tibialis anterior muscle and soleus muscle of apolipoprotein-E-deficient mice
      were examined by light and electron microscopy. By light microscopy, sarcoplasmic
      inclusions were seen in tibialis anterior muscle and 40% of type 2 myofibers were
      affected in all animals over 8 months of age. These inclusions reacted for
      nonspecific esterase, cytochrome oxidase, and myoadenylate deaminase and were
      also periodic acid Schiff positive and stained basophilic with hematoxylin.
      Moreover, they reacted immunocytochemically with an antibody specific to fragment
      17 to 24 of the published sequence of Alzheimer's cerebrovascular amyloid
      peptide. Immunoreactivity was lost when the antibody was adsorbed with the
      appropriate synthetic peptide. Ultrastructurally, the inclusions consisted of
      tubular arrays and were similar to those observed in human muscle in several
      pathological conditions. In type 1 myofibers of both tibialis anterior and soleus
      muscle, however, mitochondrial abnormalities including an increase in their
      number and size were detected, but tubular aggregates were not seen. These large
      mitochondria possessed an electron-dense inner chamber with an increased number
      of tightly packed cristae. The results obtained suggest that in these mice there
      is a disturbed lipid metabolism in skeletal muscle fibers that manifests itself
      with an accumulation of phospholipid in the form of sarcoplasmic reticulum
      tubules in the type 2 fibers and enlarged mitochondria with tightly packed
      cristae in the type 1 fibers. In addition, beta-amyloid protein was closely
      associated with the accumulated tubules and vesicles of sarcoplasmic reticulum
      and may represent dysregulation of amyloid precursor protein metabolism.

PMID- 9033258
TI  - Presenilin-1-immunoreactive neurons are preserved in late-onset Alzheimer's
      disease.
AB  - Recent studies have suggested that missense mutations in the presenilin-1 gene
      are causally related to the majority of familial early-onset Alzheimer's disease
      (AD). To examine the possible involvement of presenilin-1 in late-onset sporadic
      AD, a quantitative analysis of its distribution in the cerebral cortex of
      nondemented and AD patients was performed using immunocytochemistry.
      Stereological analyses revealed that AD brains showed a marked neuronal loss in
      the CA1 field of the hippocampus and hilus of the dentate gyrus, subiculum, and
      entorhinal cortex. In these areas, however, the fraction of neurofibrillary
      tangle (NFT)-free neurons showing presenilin-1 immunoreactivity was increased
      compared with nondemented controls. In contrast, cortical areas, which displayed
      no neuronal loss, did not show any significant increase in the fraction of
      presenilin-1-positive neurons. Moreover, presenilin-1 immunoreactivity was
      reduced in NFT-containing neurons. Thus, in AD, the fraction of NFT-free neurons
      that contained presenilin-1 varied from 0.48 to 0.77, whereas the fraction of NFT
      containing neurons that were presenilin-1 positive varied from 0.1 to 0.24.
      Together, these observations indicate that presenilin-1 may have a
      neuroprotective role and that in AD low cellular expression of this protein may
      be associated with increased neuronal loss and NFT formation.

PMID- 9033259
TI  - Immunohistochemical detection of 4-hydroxy-2-nonenal adducts in Alzheimer's
      disease is associated with inheritance of APOE4.
AB  - Cumulative oxidative damage, including lipid peroxidation, is a central component
      of cellular aging and is thought to play a role in the pathogenesis of late-onset
      Alzheimer's disease (AD). Lipid peroxidation produces several cytotoxic
      aldehydes, one of the most potent being 4-hydroxy-2-nonenal (HNE). We have shown
      previously that HNE is a potent neurotoxin that covalently modifies and cross
      links neuronal cytoskeletal protein in neuroglial cultures, suggesting that HNE
      may contribute to the pathogenesis of AD. In addition to aging, inheritance of
      the epsilon 4 allele of APOE is the other major risk factor for development of
      late-onset AD; however, the mechanisms through which aging and apolipoprotein E
      isoforms may collaborate in the onset or progression of AD are not known. We
      tested the hypothesis that HNE may yield a particular type of protein
      modification, pyrrole adduction, and that this may contribute to the pathogenesis
      of AD. Our data demonstrated that HNE formed pyrrole adducts with protein.
      Polyclonal antiserum was raised that specifically recognized HNE pyrrole adducts,
      and immunohistochemical analysis was performed on hippocampus and temporal cortex
      of 10 patients with histologically verified AD. Pyramidal neuron cytoplasm was
      immunoreactive in 4 of 4 APOE4 homozygotes, 2 of 3 APOE3/4 heterozygotes, and
      none of 3 APOE3 homozygotes (P < 0.05). The pattern of staining was highly
      suggestive of neurofibrillary tangles as the primary immunoreactive structure.
      These data suggest that differences in neuronal protein modification by HNE may
      account in part for the APOE-associated stratification of risk for late-onset AD.

PMID- 9033261
TI  - Immunohistochemical study suggesting a complementary role of kallikreins hK2 and
      hK3 (prostate-specific antigen) in the functional analysis of human prostate
      tumors.
AB  - The development of monoclonal antibodies directed against prostatic kallikrein
      hK2 prompted us to evaluate its content, along with that of hK3 (prostate
      specific antigen), in human prostate carcinoma. Seventy tumors categorized
      according to the M.D. Anderson Hospital classification (grade I to IV) were
      analyzed by immunohistochemistry. The staining intensity or the kallikrein
      content of benign prostatic hyperplasia glandular tissue (used as control) and of
      grade I tumors appeared similar. In grade II to IV tumors, histochemical data
      revealed highly variable hK2 or hK3 content in approximately 25% of tumors. Such
      patterns are consistent with a current observation related to heterogeneity of
      prostate tumors. In addition, a few tumors did not express hK3 (n = 3), hK2 (n =
      3), or both (n = 3), indicating that some growth patterns of prostatic neoplasia
      are associated with a lack of secretion or storage of hK3 or hK2 for
      immunodetection. This statement also appears relevant to metastases. It was
      interesting to note that 4% of hK3-negative tumors had detectable hK2. Because of
      the importance of hK3 as a serum marker of prostate disorder, this study
      addresses for the first time the question of the relative importance of both hK3
      and hK2 in the immunohistochemical diagnosis of prostatic tumors. We conclude
      that hK2 may add new information to prostate cancer diagnosis and
      characterization.

PMID- 9033260
TI  - Encephalitogenic potential of myelin basic protein-specific T cells isolated from
      normal rhesus macaques.
AB  - Myelin basic protein (MBP)-specific T cells are implicated in the pathogenesis of
      multiple sclerosis and are targets of selective immunotherapies. However,
      autoantigen-specific T cells can also be isolated from healthy individuals. Their
      functional potential is unknown and obviously cannot be tested in humans. We
      approached this question in a closely related primate species, the rhesus monkey.
      CD4+ T cell lines specific for MBP were isolated from normal rhesus monkeys using
      the same primary limiting dilution technique that is now widely used to generate
      human autoreactive T cell clones in vitro. Three different epitopes were
      recognized by three rhesus T cell lines isolated from three different monkeys.
      Upon activation, all lines produced interferon-gamma, interleukin-2, tumor
      necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor but
      neither interleukin-4 nor transforming growth factor-beta. The MBP-specific T
      cells were injected intravenously without adjuvant into the nonirradiated
      autologous monkey. One of the three rhesus monkeys developed an encephalomyelitis
      with a pleocytosis in the spinal fluid and perivascular infiltrates in the
      leptomeninges, spinal nerve roots and cerebral cortex. The data demonstrate that
      the normal immune repertoire of a primate species contains MBP-specific CD4+ T
      cells that are able to induce an autoimmune encephalomyelitis upon transfer into
      the nonirradiated autologous recipient.

PMID- 9033262
TI  - Nonmalignant epithelial cells, potentially invasive in human endometriosis, lack
      the tumor suppressor molecule E-cadherin.
AB  - Endometriosis is one of the most frequent diseases in gynecology. It is a
      histologically defined nonmalignant disease in which endometrium-like tissue is
      found outside the uterus (for example, peritoneum, gut, or lung). The
      pathogenesis of endometriosis is unknown, but invasive mechanisms have been
      implicated in the development of the disease. Indeed, primary cells from human
      endometriotic biopsies but not from human endometrial biopsies are invasive in an
      in vitro collagen invasion assay. In this study, these in vitro invasive
      endometriotic cells were found to be nonmalignant epithelial cells lacking E
      cadherin, which acts as an invasion suppressor molecule in carcinomas.
      Immunocytochemistry showed that the E-cadherin-negative epithelial cell type was
      increased in sections of endometriosis tissue as compared with sections of
      eutopic endometrium. On the basis of these data we propose that the E-cadherin
      negative invasive endometriotic cells seen in vitro represent the cell population
      that migrates to ectopic (extrauterine) locations and thus causes endometriosis
      in vivo. Accordingly, the loss of E-cadherin expression is postulated to
      constitute a crucial mechanism in the pathogenesis of endometriosis.

PMID- 9033263
TI  - Detection of rare RNA sequences by single-enzyme in situ reverse transcription
      polymerase chain reaction. High-resolution analyses of interleukin-6 mRNA in
      paraffin sections of lymph nodes.
AB  - To study the distribution pattern of interleukin-6 (IL-6)-producing cells in
      normal human lymph nodes, we applied the in situ reverse transcription-polymerase
      chain reaction technique. We describe a new modification of this technique for
      monitoring small amounts of specific nucleotide sequences in conventional
      paraffin sections. This technique differs in at least two respects from those
      described earlier. The two decisive steps are: 1) the reverse transcription of
      mRNA and the subsequent amplification of cDNA by polymerase chain reaction are
      performed by a new single enzyme capable of both reaction types in one and the
      same medium without buffer exchange; and 2) for the specific detection of the
      amplified cDNA, a modified version of the primed in situ labeling technique was
      used. The technique, carried out on normal human lymph nodes, traces a low load
      of IL-6 mRNA in fibroblasts, endothelial cells, and a minor population of T
      lymphocytes in the pulp region. High levels of expression were encountered in
      about 20% of perisinusoidal pulp macrophages. In addition, moderate activity was
      detectable in sinus lining cells. Because no major activity was found in the
      germinal centers of the lymphoid B follicles and in the T zone, it is suggested
      that the plasma cell differentiation ensuing from primary and secondary B-cell
      immunization is mainly effected by the sinus lining cells as well as
      perifollicular and perisinusoidal pulp macrophages capable of producing high
      amounts of IL-6.

PMID- 9033264
TI  - Amplification of the t(2; 13) and t(1; 13) translocations of alveolar
      rhabdomyosarcoma in small formalin-fixed biopsies using a modified reverse
      transcriptase polymerase chain reaction.
AB  - Detection of characteristic chromosomal translocations has aided diagnosis of the
      small round cell tumors of childhood and may help to stratify patients into
      clinical groups. The detection of the abnormalities by classical cytogenetic
      techniques has been supplemented by fluorescent in situ hybridization and reverse
      transcriptase polymerase chain reaction (RT-PCR). These techniques allow
      diagnoses to be made using only very small amounts of tumor tissue. We here
      describe a technique for the rapid and specific detection by modified reverse
      transcriptase polymerase chain reaction of characteristic chromosomal
      translocations of alveolar rhabdomyosarcoma with small amounts of formalin-fixed
      tissue as the starting material. Of 27 samples studied, 4 cases are described in
      which the detection of translocations by this method cast doubt on the original
      histopathological diagnosis. These cases demonstrate the critical diagnostic
      importance of the detection of these translocations in rhabdomyosarcoma.

PMID- 9033265
TI  - Experimental co-expression of vimentin and keratin intermediate filaments in
      human breast cancer cells results in phenotypic interconversion and increased
      invasive behavior.
AB  - The expression of intermediate filament proteins is remarkably tissue specific,
      which suggests that the intermediate filament type(s) present in cells is somehow
      related to their biological function. However, in some cancers, particularly
      malignant breast carcinoma, there is a strong indication that vimentin is co
      expressed with keratins, thus presenting as a dedifferentiated or interconverted
      (between epithelial and mesenchymal) phenotype. In the present study, we
      recapitulated the interconverted phenotype by developing stable transfectants of
      MCF-7 human breast cancer cells, termed MoVi clones, to express both vimentin and
      keratins. Overexpression of vimentin in these cells led to augmentation of
      motility and invasiveness in vitra. These activities could be transiently down
      regulated by vimentin antisense oligonucleotides in MoVi clones and MDA-MB-231
      cells (which constitutively co-express keratins and vimentin). Furthermore, in
      the MoVi experimental transfectants expressing the highest percentage of vimentin
      positive cells, their proliferative capacity, clonogenic potential, and
      tumorigenicity increased. However, the metastatic ability of the MoVi
      transfectants remained unchanged compared with MCF-7neo controls. The MDA-MB-231
      cells metastasized to axillary lymph nodes in a SCID mouse model. Finally, we
      explored the possibility that potential changes could occur with respect to cell
      surface integrins. These studies revealed a decrease in the alpha 2- and alpha 3
      containing promiscuous integrins, in addition to beta 1 containing integrins,
      concomitant with an increase in the alpha 6-containing laminin receptor integrin.
      Further functional analysis of the alpha 6 observation showed an increase in the
      baptotactic migration of MoVi transfectants toward a laminin substrate. From
      these data, it is postulated that the ability to co-express vimentin and keratins
      confers a selective advantage to breast cancer cells in their interpretation of
      signaling cues from the extracellular matrix; however the addition of vimentin
      intermediate filaments alone is not sufficient to confer the metastatic
      phenotype.

PMID- 9033266
TI  - Lysyl oxidase gene expression in the stromal reaction to in situ and invasive
      ductal breast carcinoma.
AB  - Lysyl oxidase is involved in the main pathway of collagen and elastin cross
      linking: it has a role in the maturation of fibrillar matrix proteins in
      fibrosing processes and dictates their stability against metalloproteases. The
      stromal reaction patterns in ductal breast carcinoma are known to be
      morphologically varied. This has raised the hypothesis that there might be a
      differential expression of the lysyl oxidase gene as a function of stromal
      reaction pattern. The present study investigates this potential correlation and
      the role of matrix protein cross-linking in stromal differentiation. Lysyl
      oxidase was detected by immunohistochemistry and lysyl oxidase gene expression by
      in situ hybridization. Maximal expression was observed in myofibroblasts and
      myoepithelial cells around in situ tumors and in the reactive fibrosis facing the
      invasion front of infiltrating tumors. The lysyl oxidase substrates were observed
      in parallel, resulting in the stabilization of a scar-like peritumor barrier. In
      contrast, a lack of lysyl oxidase was associated with the loose or scirrhous
      stroma accompanying invading tumors; here, in situ hybridization revealed type I
      collagen synthesis, resulting in the deposition of non-cross-linked matrix
      proteins susceptible to degradation. The early development of a cross-linked
      matrix around ductal breast carcinoma suggests a possible bost defense mechanism,
      whereas the synchronous or late stromal reaction lacking lysyl oxidase favors
      tumor dispersion.

PMID- 9033267
TI  - Cellular retinol-binding protein-1 is expressed by distinct subsets of rat
      arterial smooth muscle cells in vitro and in vivo.
AB  - Previous work (M.-L. Bochaton-Piallat, P. Ropraz, F. Gabbiani, G. Gabbiani,
      Arterioscler Thromb Vasc Biol 1996, 16:815-820) has shown that a subset of smooth
      muscle cell (SMC) clones derived from the normal rat aortic media displays an
      epithelioid phenotype similar to that of the whole SMC population cultured from
      the intimal thickening 15 days after endothelial injury (IT-15). We show here
      that the whole IT-15 SMC population and the epithelioid clones, derived either
      from the normal media or from the IT-15, express cellular retinol-binding protein
      1 (CRBP-1), a protein involved in retinoid metabolism. The expression of CRBP-1
      is accompanied by the expression of cytokeratin 8. In both whole SMC population
      cultured from IT-15 and epithelioid clones, retinoic acid modulates the
      transition from the epithelioid phenotype to the spindle phenotype, typical of
      whole SMC populations cultured from the rat normal aortic media. Moreover, after
      endothelial injury in vivo, a CRBP-1 expressing SMC subset appears transiently in
      the IT and disappears, allegedly by apoptosis, when re-endothelialization takes
      place. Our results suggest that the expression of CRBP-1 is a marker of arterial
      SMC activation after endothelial injury in vivo and that CRBP-1 and probably
      retinoids participate in this process.

PMID- 9033268
TI  - Advanced glycation end products (AGEs) co-localize with AGE receptors in the
      retinal vasculature of diabetic and of AGE-infused rats.
AB  - Advanced glycation end products (AGEs), formed from the nonenzymatic glycation of
      proteins and lipids with reducing sugars, have been implicated in many diabetic
      complications; however, their role in diabetic retinopathy remains largely
      unknown. Recent studies suggest that the cellular actions of AGEs may be mediated
      by AGE-specific receptors (AGE-R). We have examined the immunolocalization of
      AGEs and AGE-R components R1 and R2 in the retinal vasculature at 2, 4, and 8
      months after STZ-induced diabetes as well as in nondiabetic rats infused with AGE
      bovine serum albumin for 2 weeks. Using polyclonal or monoclonal anti-AGE
      antibodies and polyclonal antibodies to recombinant AGE-R1 and AGE-R2,
      immunoreactivity (IR) was examined in the complete retinal vascular tree after
      isolation by trypsin digestion. After 2, 4, and 8 months of diabetes, there was a
      gradual increase in AGE IR in basement membrane. At 8 months, pericytes, smooth
      muscle cells, and endothelial cells of the retinal vessels showed dense
      intracellular AGE IR. AGE epitopes stained most intensely within pericytes and
      smooth muscle cells but less in basement membrane of AGE-infused rats compared
      with the diabetic group. Retinas from normal or bovine-serum-albumin-infused rats
      were largely negative for AGE IR. AGE-R1 and -R2 co-localized strongly with AGEs
      of vascular endothelial cells, pericytes, and smooth muscle cells of either
      normal, diabetic, or AGE-infused rat retinas, and this distribution did not vary
      with each condition. The data indicate that AGEs accumulate as a function of
      diabetes duration first within the basement membrane and then intracellularly, co
      localizing with cellular AGE-Rs. Significant AGE deposits appear within the
      pericytes after long-term diabetes or acute challenge with AGE infusion
      conditions associated with pericyte damage. Co-localization of AGEs and AGE-Rs in
      retinal cells points to possible interactions of pathogenic significance.

PMID- 9033269
TI  - HIV is trapped and masked in the cytoplasm of lymph node follicular dendritic
      cells.
AB  - To gain further insight into the pathogenesis of human immunodeficiency virus
      (HIV) infection, lymph nodes from seven asymptomatic HIV+ subjects were analyzed
      during the latent phase of disease. Both ultrastructural and immunohistochemical
      analyses revealed that, in all of the cases, plasma cells producing IgM/gamma
      were present in germinal centers. Secreted immunoglobulins formed extracellular
      deposits mimicking the follicular dendritic cell network. Immunoglobulin produced
      by germinal center plasma cells are specific for HIV because they bind the HIV
      env protein gp 120. Plasma cells producing antibodies with the same specificity
      were also abundant in the extrafollicular regions of lymph nodes. During the
      latent phase of infection, the virus largely accumulates within the germinal
      centers. Therefore, extracellular immunoglobulin may form immune complexes, as
      shown by the presence of HIV-specific antibodies, HIV particles, and complement
      components C3c, C3d, and C1q in the interdendritic spaces. When the
      ultrastructural localization of HIV in germinal centers was analyzed, abundant
      virus particles were found in the interdendritic spaces. In addition to this
      extracellular localization of HIV, receptor-mediated endocytosis of viral
      particles by follicular dendritic cells was observed. Complete HIV particles were
      found within the endosomal compartment of the follicular dendritic cells and, as
      complete viral particles, free in the cytoplasm, indicating that the virus may
      escape from the endocytic compartment. As the virus is abundant in the cytoplasm,
      this event leads to formation of a hidden reservoir within follicular dendritic
      cells. In this location, HIV escapes recognition by cytotoxic T lymphocytes. In
      contrast, virus budding indicating a productive infection of follicular dendritic
      cells that would render them susceptible to T-cell-mediated lysis has been seldom
      observed.

PMID- 9033270
TI  - Fascin, a sensitive new marker for Reed-Sternberg cells of hodgkin's disease.
      Evidence for a dendritic or B cell derivation?
AB  - Immunohistochemical localization of human fascin, a distinct 55-kd actin-bundling
      protein, was determined for a wide variety of lymphoid tissues (364 specimens
      total). In non-neoplastic tissues, reactivity was highly selective and localized
      predominantly in dendritic cells. In the thymus, this protein was distinctly
      localized to medullary dendritic cells. In reactive nodes, interdigitating
      reticulum cells of T zones, cells in subcapsular areas, and cells of the
      reticular network were reactive, with variable reactivity observed for follicular
      dendritic cells. Splenic dendritic cells of the white pulp and sinus-lining cells
      of the red pulp were reactive. Endothelial cells of all tissues exhibited
      variable reactivity. Lymphoid cells, myeloid cells, and plasma cells were
      uniformly nonreactive. In the peripheral blood, only dendritic (veiled) cells
      were reactive for fascin. A striking finding was observed for cases of Hodgkin's
      disease (total 187 cases). In all cases of nodular sclerosis (132), mixed
      cellularity (34), lymphocyte depletion (2), and unclassified types (5), all or
      nearly all Reed-Sternberg cells and variants were immunoreactive for fascin.
      Neoplastic cells exhibited strong diffuse cytoplasmic staining and frequently
      assumed dendritic shapes, particularly in the nodular sclerosis type, producing
      an interdigitating meshwork or syncytial network of cells. In cases of mixed
      cellularity type, neoplastic cells generally appeared more discrete. In all 14
      cases of nodular lymphocyte predominance type, L&H variants were nonreactive. By
      contrast, neoplastic lymphoid cells of only 24 of 156 (15%) other lymphoid
      neoplasms (127 B cell, 27 T cell, and two null cell evaluated) were reactive for
      fascin. Fascin represents a highly effective marker for detection of certain
      dendritic cells in normal and neoplastic tissues, is an extremely consistent
      marker for Reed-Sternberg cells and variants of Hodgkin's disease (except L&H
      types), and may be helpful to distinguish between Hodgkin's disease and non
      Hodgkin's lymphoma in difficult cases. The staining profile for fascin raises the
      possibility of a dendritic cell derivation, particularly an interdigitating
      reticulum cell, for the neoplastic cells of Hodgkin's disease, notably in nodular
      sclerosis type. However, as fascin expression may be induced by Epstein-Barr
      virus infection of B cells, the possibility that viral induction of fascin in
      lymphoid or other cell types must also be considered in Epstein-Barr virus
      positive cases.

PMID- 9033272
TI  - Induction of plasminogen activator inhibitor 1 gene expression in murine liver by
      lipopolysaccharide. Cellular localization and role of endogenous tumor necrosis
      factor-alpha.
AB  - We previously demonstrated that lipopolysaccharide (LPS) induces plasminogen
      activator inhibitor 1 (PAI-1) gene expression primarily in endothelial cells in
      most organs of the mouse, with maximal induction by 3 hours. Here we show that
      induction in the liver occurs in a distinctly different pattern. For example, the
      increase in PAI-1 mRNA in liver was biphasic with an initial peak at 1 to 2 hours
      and a second peak at 6 to 8 hours. Moreover, in situ hybridization experiments
      revealed that PAI-1 mRNA was induced in both endothelial cells and hepatocytes.
      The endothelial cell response was monophasic and maximal between 1 and 4 hours,
      whereas the hepatocyte response was biphasic, peaking at 2 hours and again at 6
      to 8 hours. To determine possible mechanisms involved in the induction of PAI-1
      by LPS, we analyzed the tissues for changes in tumor necrosis factor (TNF)-alpha
      LPS caused a rapid induction of TNF-alpha mRNA in Kupffer cells, detectable
      within 15 minutes. Pretreatment of mice with anti-TNF antiserum before challenge
      with LPS reduced the subsequent increase in plasma levels of PAI-1 by 50 to 70%
      and significantly reduced the level of induction of PAI-1 mRNA in the liver at
      both early and late times. Pretreatment appeared to inhibit induction primarily
      within hepatocytes. These results suggest that LPS may induce PAI-1 in
      endothelial cells and hepatocytes by different mechanisms.

PMID- 9033271
TI  - Analysis of chronic rejection and obliterative arteriopathy. Possible
      contributions of donor antigen-presenting cells and lymphatic disruption.
AB  - Sequential analysis of changes that lead to chronic rejection was undertaken in
      an animal model of chronic rejection and obliterative arteriopathy. Brown Norway
      rats are pretreated with a Lewis bone marrow infusion or a Lewis orthotopic liver
      allograft and a short course of immunosuppression. They are challenged 100 days
      later with a Lewis heterotopic heart graft without immunosuppression. The heart
      grafts in both groups undergo a transient acute rejection, but all rats are
      operationally tolerant; the heart grafts are accepted and remain beating for more
      than 100 days. Early arterial remodeling, marked by arterial bromodeoxyuridine
      incorporation, occurred in both groups between 5 and 30 days during the transient
      acute rejection. It coincided with the presence of interstitial (but not arterial
      intimal) inflammation and lymphatic disruption and resulted in mild intimal
      thickening. Significant arterial narrowing occurred only in the bone-marrow
      pretreated rats between 60 and 100 days. It was associated with T lymphocyte and
      macrophage inflammation of the heart graft that accumulated in the endocardium
      and arterial intima and adventitia near draining lymphatics. There also was loss
      of passenger leukocytes from the heart graft, up-regulation of cytokine mRNA and
      major histocompatibility class II on the endothelium, and focal disruption of
      lymphatics. In contrast, long-surviving heart grafts from the Lewis orthotopic
      liver allograft pretreated group are near normal and freedom from chronic
      rejection in this group was associated with persistence of donor major
      histocompatibility class-II-positive hematolymphoid cells, including OX62+ donor
      dendritic cells. This study offers insights into two different aspects of chronic
      rejection: 1) possible mechanisms underlying the persistent immunological injury
      and 2) the association between immunological injury and the development of
      obliterative arteriopathy. Based on the findings, it is not unreasonable to raise
      the testable hypothesis that direct presentation of alloantigen by donor antigen
      presenting cells is required for long-term, chronic-rejection-free allograft
      acceptance. In addition, chronic intermittent lymphatic disruption is implicated
      as a possible mechanism for the association between chronic interstitial
      allograft inflammation and the development of obliterative arteriopathy.

PMID- 9033273
TI  - Selective bipotential differentiation of mouse embryonic hepatoblasts in vitro.
AB  - A line of hepatic endoderm cells, hepatoblast cell line 3 (HBC-3), was derived
      from the liver diverticulum of the mouse on day 9.5 of gestation by culture on a
      mitomycin C treated STON+ feeder layer in a hepatoblast culture medium consisting
      of Dulbecco's modified Eagle's medium, nonessential amino acids, fetal calf
      serum, and beta-mercaptoethanol. This line, HBC-3, stains positively for alpha
      fetoprotein, albumin, and cytokeratin 14 (CK-14), protein markers expressed by
      the embryonic liver diverticulum, indicating that HBC-3 cells retain an
      undifferentiated hepatoblast phenotype. HBC-3 cells acquire hepatocyte-like
      ultrastructural characteristics, including bile canaliculi, peroxisomes, and
      glycogen granules, when maintained in culture for 3 weeks without passage.
      Treatment with dimethylsulfoxide or sodium butyrate induces a rapid hepatocytic
      differentiation. The cells cease to express alpha-fetoprotein and CK-14, maintain
      albumin expression, and become positive for glucose-6-phosphatase activity (a
      profile consistent with differentiation along the hepatocyte lineage). On
      Matrigel, HBC-3 cells form elaborate ductular structures, which are positive for
      gamma-glutamyl transpeptidase and CK-14 and CK-19 and do not express detectable
      amounts of albumin, a phenotypic change consistent with differentiation along the
      bile ductular lineage. Thus, HBC-3 cells behave in culture as bipotential
      hepatoblasts and provide a model system to identify factors that regulate
      bipotential differentiation in the liver.

PMID- 9033274
TI  - Immunological evidence for hypochlorite-modified proteins in human kidney.
AB  - Oxygen radicals and oxidatively modified proteins seem to participate in
      degenerative vascular and inflammatory diseases. Factors that contribute to the
      development of atherosclerosis, eg, oxidation of low-density lipoproteins (LDLs),
      may also contribute to glomerulosclerosis. Although the nature of the in vivo
      oxidants remains unknown, recent findings indicated that the myeloperoxidase
      (MPO)-H2O2-halide system could play an important role in modification of
      (lipo)proteins in human tissues. MPO, the enzyme responsible for hypochlorite
      (HOCl/OCl-) formation, is present in human atherosclerotic lesions and in
      inflammatory conditions. In the present study, MPO was identified by Western blot
      analysis and immunohistochemical technique in diseased human kidney either with
      primarily sclerotic or inflammatory lesions. Furthermore, the presence of HOCl
      modified proteins was demonstrated in diseased renal tissues using a specific
      monoclonal antibody (clone 2D10G9), raised against HOCl-modified LDL, that does
      not cross-react with native LDL or Cu(2+)-, 4-hydroxynonenal-, or malondialdehyde
      modified LDL. The antibody recognized HOCl-modified proteins in glomerular and
      tubulointerstitial inflammatory and fibrotic lesions and pronounced
      immunostaining was demonstrated in mononuclear cells. LDL or human serum albumin
      oxidized by HOCl in vitro, but not native LDL or human serum albumin, effectively
      competed with epitopes in diseased kidney for antibody binding. Western blot
      analysis in diseased kidney protein samples revealed at least two major proteins
      recognized by the anti-HOCl-modified protein monoclonal antibody. Densitometric
      evaluation of immunoreactive bands obtained under these conditions demonstrated
      that expression of HOCl-modified proteins is tightly coupled to expression of
      immunoreactive MPO in the same tissue samples. From our studies it is proposed
      that oxidation of proteins by HOCl might be a leading event in glomerular and
      tubulointerstitial injury. By this mechanism, mononuclear cells, a permanent
      source for MPO, may play a key role in the development of nephrosclerosis,
      glomerulo-clerosis, and tubulointerstitial fibrosis, respectively.

PMID- 9033275
TI  - Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage
      in the central nervous system of mice with relapses of chronic experimental
      autoimmune encephalomyelitis.
AB  - Chemokines are secreted peptides that exhibit selective chemoattractant
      properties for target leukocytes. Two subfamilies, alpha- and beta-chemokines,
      have been described, based on structural, genetic, and functional considerations.
      In acute experimental autoimmune encephalomyelitis (EAE), chemokines are up
      regulated systemically and in central nervous system (CNS) tissues at disease
      onset. Functional significance of this expression was supported by other studies;
      intervention with an antichemokine antibody abrogated passive transfer of EAE,
      and chemokines expressed in brains of transgenic mice recruited appropriate
      leukocyte populations into the CNS compartment. Chemokine expression in the more
      relevant circumstance of chronic EAE has not been addressed. We monitored the
      time course and cellular sources of chemokines (monocyte chemoattractant protein
      1, macrophage inflammatory protein-1 alpha, interferon-gamma-inducible protein of
      10 kd, KC, and regulated on activation, normal T-cell expressed and secreted
      cytokine) in CNS and peripheral tissues during spontaneous relapses of chronic
      EAE. We found coordinate chemokine up-regulation in brain and spinal cord during
      clinical relapse, with expression confined to CNS tissues. Monocyte
      chemoattractant protein-1, interferon-gamma-inducible protein of 10 kd, and KC
      were synthesized by astrocytic cells, whereas macrophage inflammatory protein-1
      alpha and regulated on activation, normal T-cell expressed and secreted cytokine
      were elaborated by infiltrating leukocytes. The results demonstrate stringent
      regulation of multiple chemokines in vivo during a complex organ-specific
      autoimmune disease. We propose that chemokine expression links T-cell antigen
      recognition and activation to subsequent CNS inflammatory pathology in chronic
      relapsing EAE.

PMID- 9033276
TI  - Experimental production and modulation of human cytotoxic dermatitis in human
      murine chimeras.
AB  - Human dermatitis-involving cytotoxic interaction between effector lymphocytes and
      epithelial target cells has thus far been documented in vivo only as naturally
      occurring disease or as an iatrogenic complication of organ engraftment. In this
      report, we reproduce human cytotoxic dermatitis via local microinjection of
      heterologous human lymphocytes into human skin xenografted to mice with severe
      combined immune deficiency syndrome. Injection sites develop progressive T cell
      epidermotropism culminating in cytotoxic dermatitis resembling human lichen
      planus within 4 weeks. Effector T cells express a CD8+, TIA-1+ phenotype,
      proliferate locally, express interleukin-2 surface receptors, and demonstrate
      interferon-gamma mRNA induction after microinjection. Migration of these T cells
      into the epidermis is closely linked to experimental induction and coincident
      expression of intercellular adhesion molecule by keratinocytes. T cell apposition
      to keratinocytes is associated with endonuclease-mediated DNA fragmentation
      (apoptosis) in the latter cell type. Intraepidermal T cell migration and related
      lesion formation is partially abrogated by systemic administration of antisense
      oligonucleotide to ICAM-1 mRNA. These findings demonstrate that human cytotoxic
      tissue injury directed against epithelial targets can be produced and modulated
      in chimeric mice.

PMID- 9033277
TI  - Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are
      deficient in T cell co-stimulatory molecules and are impaired as antigen
      presenting cells.
AB  - Immune surveillance of skin cancer involves the stimulation of effector T cells
      by tumor-derived antigens and antigen-presenting cells (APCs). An effective APC
      must not only display processed antigen in the context of MHC molecules but also
      express co-stimulatory molecules that are required to fully activate T cells. One
      of the most common cutaneous neoplasms is basal cell carcinoma. To investigate
      expression of the co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) on tumor
      associated dendritic cells (TADCs), cryosections from basal cell carcinomas were
      immunostained. In basal cell carcinomas, only 1 to 2% of intratumor and 5 to 10%
      of peritumor APCs expressed CD80 or CD86. In contrast, biopsies of
      immunological/inflammatory dermatoses revealed that 38 to 73% of APCs expressed
      CD80 and CD86. To further evaluate their phenotype and function, TADCs were
      isolated from tissue samples of basal cell carcinomas; they were non-adherent to
      plastic, displayed a typical dendritic morphology, and expressed high levels of
      major histocompatibility class II molecules on their surface. When TADCs were
      compared with dendritic cells from blood for presentation of superantigens
      (staphylococcal enterotoxins A and B) to resting autologous T cells, TADCs were
      consistently weaker stimulators of T cell proliferation than blood dendritic
      cells. When analyzed by flow cytometry, TADCs expressed high levels of HLA-DR,
      but only 5 to 10% co-expressed CD80 or CD86. A 3-day culture in
      granulocyte/macrophage colony-stimulating factor-containing medium partially
      reconstituted the TADC expression of CD80 and CD86 as well as their
      immunostimulatory capacity. Thus, in this common skin cancer, although there are
      prominent collections of HLA-DR-positive APCs in and around tumor cells, the
      TADCs are deficient in important co-stimulatory molecules as well as being weak
      stimulators of T cell proliferation. The paucity of co-stimulatory molecule
      expression and functional activity of TADCs may explain why the local T
      lymphocytic infiltrate fails to become fully activated to eradicate adjacent
      tumor cells. From a clinical perspective, these findings suggest a novel
      immunotherapeutic strategy targeting T cell co-stimulatory molecules on
      professional APCs in cutaneous oncology.

PMID- 9033278
TI  - Increased expression of matrix metalloproteinases in vivo in scleritis tissue and
      in vitro in cultured human scleral fibroblasts.
AB  - Scleritis is a sight-threatening inflammatory disorder of the eye characterized
      by the degradation of scleral matrix. Matrix metalloproteinases (MMPs) are
      ubiquitous proteolytic enzymes important in physiological and pathological
      processes, the activity of which is stringently controlled by the action of a
      family of natural antagonists, the tissue inhibitors of matrix metalloproteinases
      (TIMPs). We hypothesized that enhanced expression of MMPs, without the negative
      regulatory influence of TIMPs, may be a key feature of tissue destruction in
      inflammatory eye diseases, such as scleritis. The aim of this study was to
      localize and characterize cells expressing MMPs and TIMPs in sclera affected by
      necrotizing scleritis and, in a parallel study, to establish whether cytokines
      modulate MMP expression in cultured human scleral fibroblasts. In situ
      hybridization and immunohistochemical analyses indicated that resident scleral
      fibroblasts as well as inflammatory cells such as macrophages and T lymphocytes
      express stromelysin, gelatinase B, and TIMP-1 in necrotizing scleritis tissue. In
      addition, cytoplasmic immunoreactivity for tumor necrosis factor-alpha, an
      inducer of MMPs, was detected in infiltrating inflammatory cells. Cultured
      scleral fibroblasts stimulated with the combination of interleukin-1 alpha plus
      tumor necrosis factor-alpha increased TIMP-1 mRNA twofold above constitutive
      levels. By contrast, these cytokines induced a sevenfold increase in the steady
      state levels of stromelysin mRNA. Using Western blotting, stromelysin and TIMP-1
      protein production paralleled mRNA induction in cytokine-stimulated human scleral
      fibroblasts. Culture supernatants harvested from cytokine-stimulated human
      scleral fibroblasts were subjected to sodium dodecyl sulfate polyacrylamide gel
      electrophoresis gelatin substrate zymography. Our results revealed a prominent 92
      kd gelatinolytic band corresponding to gelatinase B, which was inducible with
      interleukin-1 alpha. These data provide evidence for our hypothesis, that an
      imbalance between enzyme/inhibitor ratios may be the underlying mechanism of the
      tissue destruction characteristic of scleritis. Our results demonstrate the
      potential involvement of MMPs and their modulation by cytokines produced by
      infiltrating inflammatory cells in destructive ocular inflammation.

PMID- 9033279
TI  - No evidence of HTLV-I proviral integration in lymphoproliferative disorders
      associated with cutaneous T-cell lymphoma.
AB  - Several recent studies have reported detection of HTLV-I genetic sequences in
      patients with cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and
      Sezary syndrome. The purpose of this study was to determine whether HTLV-I was
      detectable in lesional tissues of patients suffering from diseases known to be
      associated with CTCL. Thirty-five cases were obtained from diverse geographical
      locations including Ohio, California, Switzerland, and Japan. Six of them had
      concurrent CTCL. Cases were analyzed using a combination of genomic polymerase
      chain reaction (PCR)/ Southern blot, dot blot, and Southern blot analyses. All
      assays were specific for HTLV-I provirus. Sensitivity ranged from approximately
      10(-6) for PCR-based studies to 10(-2) for unamplified genomic blotting. Lesional
      DNA from patients with lymphomatoid papulosis (fourteen cases), Hodgkin's disease
      (twelve cases), and CD30+ large-cell lymphoma (nine cases) was tested for the
      HTLV-I proviral pX region using a genomic PCR assay followed by confirmatory
      Southern blot analysis with a nested oligonucleotide pX probe. All cases were
      uniformly negative. All of the Hodgkin's disease cases, eight of the large-cell
      lymphoma cases, and six of the lymphomatoid papulosis cases were then subjected
      to dot blot analysis of genomic DNA using a full-length HTLV-I proviral DNA probe
      that spans all regions of the HTLV-I genome. Again, all cases were negative.
      Finally, eleven of the Hodgkin's disease cases were also subjected to Southern
      blot analysis of EcoRI-digested genomic DNA using the same full-length HTLV-I
      probe. Once again, all cases were negative. These findings indicated that,
      despite utilization of a variety of sensitive and specific molecular biological
      methods, HTLV-I genetic sequences were not detectable in patients with CTCL
      associated lymphoproliferative disorders. These results strongly suggest that the
      HTLV-I retrovirus is not involved in the pathogenesis of these diseases.

PMID- 9033280
TI  - Lesional psoriatic T cells contain the capacity to induce a T cell activation
      molecule CDw60 on normal keratinocytes.
AB  - In this report we demonstrate, that in psoriatic skin, basal and suprabasal
      keratinocytes express CDw60. The CDw60-specific monoclonal antibody, UM4D4, has
      recently been shown to recognize the 9-O-acetylated disialosyl group on
      ganglioside GD3. The CDw60 antigen on cultured keratinocytes also seems to be
      identical with the 9-O-acetylated disialosyl group, because the anti-UM4D4
      binding was markedly reduced after neuraminidase treatment of keratinocytes. To
      examine whether factors from T cells in psoriatic lesions are responsible for the
      overexpression of CDw60 on keratinocytes, T cell lines obtained from lesional
      skin were initiated and cloned by limiting dilution. Factors released from 19 of
      19 activated T cell clones up-regulated CDw60 expression on cultured normal
      keratinocytes. T-cell-secreted cytokines, including interleukin (IL)-2, IL-3, IL
      4, IL-6, IL-13, transforming growth factor-beta, granulocyte/macrophage colony
      stimulating factor, and interferon-gamma were tested for their capacity to
      modulate keratinocyte CDw60 expression. IL-4 and IL-13 strongly up-regulated the
      expression of CDw60; by contrast, interferon-gamma down-regulated keratinocyte
      CDw60 expression. Interestingly, IL-13 may in part be responsible for the T-cell
      induced up-regulation of CDw60, because anti-IL-13 partly neutralized this effect
      of the T cell supernatant. In conclusion, CDw60 expression on psoriatic epidermal
      keratinocytes is likely induced by intralesionally activated T cells and may in
      part be due to IL-13. These findings would represent a novel mechanism by which T
      cells participate in the pathogenesis of psoriasis.

PMID- 9033281
TI  - Gains, losses, and amplifications of DNA sequences evaluated by comparative
      genomic hybridization in chondrosarcomas.
AB  - Comparative genomic hybridization was used to search for previously unknown gains
      and losses of DNA sequences along all chromosome arms in 29 chondrosarcoma
      specimens obtained from 23 patients. Extensive genetic aberrations, with a mean
      of 6 changes per tumor (range, 1 to 24), were detected in 21 of the 29 samples
      analyzed (72%). The majority of these changes were gains of whole chromosomes or
      whole chromosome arms. Gains of DNA sequence copy number were most frequent at
      20q (38%), 17p (38%), 20p (31%), 1cen-q24 (28%), and 14q23-qter (28%). High-level
      amplifications of small chromosome regions were sporadic, detected in only 17% of
      the samples. The only recurrent high-level amplification, seen in two tumors
      (7%), affected the minimal common region 12cen-q15. Other amplifications, each
      encountered only once, involved 1p33-p35, 2p23-pter, 4p, 6p22-pter, 18q12-q22,
      19p13.2, 19q13.2, and 20q13.1. Losses of DNA sequences were rare and were most
      commonly observed at 6cen-q22 (17%) and 9p (17%).

PMID- 9033283
TI  - Cyclin D1 expression in invasive breast cancer. Correlations and prognostic
      value.
AB  - Cyclin D1 overexpression, detected by standard immunohistochemistry, was
      correlated with other prognostic variables and its prognostic value was evaluated
      in a group of 148 invasive breast cancers with long-term follow-up.
      Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test)
      with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear
      volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with
      estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1
      overexpression and histological type (P = 0.0001). Positive cyclin D1 staining
      was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4
      invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal
      cancers, 52 were positive, and all 6 medullary carcinomas were negative. There
      were no significant correlations with lymph node status, tumor size, or DNA
      ploidy. In survival analysis, cyclin D1 overexpression did not provide
      significant univariate or multivariate prognostic value. In conclusion, cyclin D1
      is mainly overexpressed in the well differentiated and lobular types of invasive
      breast cancer and is strongly associated with estrogen receptor positivity. It is
      negatively correlated with the proliferation marker mitoses count and with the
      differentiation markers nuclear area and nuclear volume. However, cyclin D1
      overexpression does not seem to have prognostic value in invasive breast cancer
      when no adjuvant treatment is given.

PMID- 9033282
TI  - Differential expression of cytokeratin mRNA and protein in normal prostate,
      prostatic intraepithelial neoplasia, and invasive carcinoma.
AB  - The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was
      investigated in normal prostate, prostatic intraepithelial neoplasia (PIN)
      lesions, and invasive carcinoma using in situ hybridization. Protein localization
      was carried out in adjacent sections using immunohistochemistry and correlated
      with mRNA expression. Snap-frozen human prostate samples including 22 examples of
      normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were
      examined. CK5 and -14 mRNA and protein were prominently expressed only in the
      basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal
      cells of the most of the PIN lesions but was seen at a low level in some PIN
      lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the
      cell that makes up the PIN lesions is derived from a basal cell, CK14 translation
      is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein
      were constitutively expressed in all epithelia of normal and abnormal prostate
      tissues. CK19 mRNA and protein were persistently expressed in both basal and
      luminal cells of the tubular portion of normal glands as well as PIN lesions, but
      were expressed heterogeneously in both basal and luminal cells of normal alveoli.
      CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not
      detected either in normal or in abnormal prostate tissues. In conclusion, the
      expression of CK19 in PIN lesions is similar to its tubular expression and would
      support an origin of PIN lesions from this structure rather than the alveolar
      portion of the glands. The similar cytokeratin expression between PIN lesions and
      invasive carcinoma further supports the concept that PIN is a precursor lesion of
      invasive carcinoma.

PMID- 9033284
TI  - Role of nitric oxide in tumor microcirculation. Blood flow, vascular
      permeability, and leukocyte-endothelial interactions.
AB  - The present study was designed to define the role of nitric oxide (NO) in tumor
      microcirculation, through the direct intravital microcirculatory observations
      after administration of NO synthase (NOS) inhibitor and NO donor both regionally
      and systemically. More specifically, we tested the following hypotheses: 1)
      endogenous NO derived from tumor vascular endothelium and/or tumor cells
      increases and/or maintains tumor blood flow, decreases leukocyte-endothelial
      interactions, and increases vascular permeability, 2) exogenous NO can increase
      tumor blood flow via vessel dilatation and decrease leukocyte-endothelial
      interactions, and 3) NO production and tissue responses to NO are tumor
      dependent. To this end, a murine mammary adenocarcinoma (MCaIV) and a human colon
      adenocarcinoma (LS174T) were implanted in the dorsal skinfold chamber in C3H and
      severe combined immunodeficient mice, respectively, and observed by means of
      intravital fluorescence microscopy. Both regional and systemic inhibition of
      endogenous NO by N omega-nitro-L-arginine methyl ester (L-NAME; 100 mumol/L
      superfusion or 10 mg/kg intravenously) significantly decreased vessel diameter
      and local blood flow rate. The diameter change was dominant on the arteriolar
      side. Superfusion of NO donor (spermine NO, 100 mumol/L) increased tumor vessel
      diameter and flow rate, whereas systemic injection of spermine NO (2.62 mg/kg)
      had no significant effect on these parameters. Rolling and stable adhesion of
      leukocytes were significantly increased by intravenous injection of L-NAME. In
      untreated animals, both MCaIV and LS174T tumor vessels were leaky to albumin.
      Systemic NO inhibition significantly attenuated tumor vascular permeability of
      MCaIV but not of LS174T tumor. Immunohistochemical studies, using polyclonal
      antibodies to endothelial NOS and inducible NOS, revealed a diffuse pattern of
      positive labeling in both MCaIV and LS174T tumors. Nitrite and nitrate levels in
      tumor interstitial fluid of MCaIV but not of LS174T were significantly higher
      than that in normal subcutaneous interstitial fluid. These results support our
      hypotheses regarding the microcirculatory response to NO in tumors. Modulation of
      NO level in tumors is a potential strategy for altering tumor hemodynamics and
      thus improving oxygen, drug, gene vector, and effector cell delivery to solid
      tumors.

PMID- 9033285
TI  - Lipid lowering: an important factor in preventing adriamycin-induced heart
      failure.
AB  - The contribution of lipid lowering in protection against adriamycin
      cardiomyopathy achieved by probucol, an antioxidant and a lipid-lowering drug,
      was assessed by comparing its beneficial effects with that of lovastatin, another
      lipid-lowering drug with no known antioxidant properties. Adriamycin (cumulative
      dose, 15 mg/kg body weight) was given to rats in 6 equal injections
      (intraperitoneally) over a period of 2 weeks. Probucol (cumulative dose, 120
      mg/kg body weight) or lovastatin (cumulative dose, 48 mg/kg body weight) was
      given in 12 equal injections (intraperitoneally) before and concurrent with
      adriamycin. After 3 weeks of post-treatment with adriamycin, congestive heart
      failure, ascites, congested liver, and depressed cardiac function were seen.
      Adriamycin treatment decreased glutathione peroxidase activity and increased
      lipid peroxidation. Adriamycin increased plasma triglycerides, total cholesterol,
      and high- and low-density lipoproteins. Myocardial triglycerides and total
      cholesterol were also increased. Probucol completely prevented the development of
      congestive heart failure and normalized myocardial and plasma triglycerides and
      total cholesterol, and significantly decreased plasma high- and low-density
      lipoproteins. Lovastatin significantly attenuated but did not completely prevent
      cardiomyopathic changes due to adriamycin. Lovastatin decreased plasma total
      cholesterol and low-density lipoproteins as well as myocardial triglycerides and
      total cholesterol. Plasma triglycerides and high-density lipoproteins were still
      high in the adriamycin plus lovastatin group. Probucol improved glutathione
      peroxidase activity and reduced lipid peroxidation whereas lovastatin had no
      effect on these adriamycin-induced changes. These data suggest that adriamycin
      cardiomyopathy is associated with an antioxidant deficit as well as increased
      myocardial and plasma lipids. Complete protection by probucol against adriamycin
      induced congestive heart failure may be due to the unique combination of its
      antioxidant and lipid-lowering properties.

PMID- 9033286
TI  - Inorganic fluoride. Divergent effects on human proximal tubular cell viability.
AB  - Fluoride (F) is a widely distributed nephrotoxin with exposure potentially
      resulting from environmental pollution and from fluorinated anesthetic use (eg,
      isoflurane). This study sought to characterize some of the subcellular
      determinants of fluoride cytotoxicity and to determine whether subtoxic F
      exposure affects tubular cell vulnerability to superimposed ATP depletion and
      nephrotoxic attack. Human proximal tubular cells (HK-2) were cultured with
      differing amounts of NaF (0 to 20 mmol/L, overlapping with clinically relevant
      intrarenal/urinary levels after fluorinated anesthetic use). After completing 24
      hour exposures, cell injury was determined (vital dye uptake). Fluoride effects
      on cell deacylation ([3]H-C20:4 release) and PLA2 activity were also assessed. To
      determine whether subtoxic F exposure alters tubular cell susceptibility to
      superimposed injury, cells were exposed to subtoxic NaF doses for 0 to 24 hours
      and then challenged with simulated ischemia (ATP depletion plus Ca2+ overload) or
      a clinically relevant nephrotoxic insult (myoglobin exposure). NaF induced dose
      dependent cytotoxicity (up to approximately 90% vital dye uptake and increased
      [3H]C20:4 release). Extracellular Ca2+ chelation (EGTA) and PLA2 inhibitor
      therapy (aristolochic acid, dibucaine, or mepacrine) each conferred significant
      protective effects. When subtoxic NaF doses were applied, partial cytosolic PLA2
      depletion rapidly developed (approximately 85% within 3 hours, determined on cell
      extracts). These partially PLA2-depleted cells were markedly resistant to ATP
      depletion/Ca2+ ionophore injury and to myoglobin-induced attack (approximately
      50% decrease in cell death). We conclude that 1) F induces dose-dependent
      cytotoxicity in cultured human proximal tubular cells, 2) this occurs, in part,
      via Ca(2+)- and PLA2-dependent mechanism(s), 3) partial cytosolic PLA2 depletion
      subsequently results, and 4) subtoxic fluoride exposure can acutely increase cell
      resistance to further attack. Reductions in cytosolic PLA2 activity could
      potentially contribute to this result.

PMID- 9033289
TI  - The heritage of the Southern Thoracic Surgical Association.

PMID- 9033288
TI  - Vascular wound healing and neointima formation induced by perivascular electric
      injury in mice.
AB  - Vascular interventions for atherothrombotic disease frequently induce neointima
      formation, which can contribute to restenosis of blood vessels. As the molecular
      mechanisms of this process remain largely unknown, quantitative models of
      arterial injury in transgenic animals may be useful to study this process at the
      genetic level. Here, an injury model is proposed in which surgically exposed
      femoral arteries in mice were injured perivascularly via a single delivery of an
      electric current. Transmission electron microscopy, light microscopy, and
      immunohistochemistry revealed that electric injury destroyed all medial smooth
      muscle cells, denuded the injured segment of intact endothelium, and transiently
      induced platelet-rich mural thrombosis. A vascular wound-healing response
      resulted that was characterized by degradation of the mural thrombus, transient
      infiltration of the vessel wall by inflammatory cells, and progressive removal of
      the necrotic debris. Topographic analysis revealed repopulation of the media and
      accumulation in the neointima of smooth muscle cells originating from the
      uninjured borders and progressing into the necrotic center. Within 3 weeks after
      injury, a neointima of 0.026 +/- 0.003 mm2 (n = 7 arteries) was formed that
      contained a maximum of 12 +/- 1 layers of smooth muscle alpha-actin
      immunoreactive cells. Evans blue staining in five electrically injured arteries
      revealed a denuded distance of 2.8 +/- 0.2 mm immediately after injury, which
      became progressively re-endothelialized from the uninjured borders to 2.2 +/-
      0.08 mm (P = 0.013 vs freshly injured by analysis of variance), 0.8 +/- 0.22 mm
      (P < 0.001), and 0.005 +/- 0.003 mm (P < 0.001) within 2, 7, and 14 days after
      injury, respectively. Analysis of 5'-bromo-2'-deoxyuridine incorporation revealed
      that a maximum of 35 +/- 10% endothelial cells proliferated within 2 days after
      injury and that in the media and neointima, a maximum of, respectively, 12 +/- 2%
      and 18 +/- 3% smooth muscle cells proliferated within 2 weeks after injury. Thus,
      electric injury of arteries provides a model of vascular wound healing with
      arterial neointima formation and re-endothelialization that may be useful for the
      genetic analysis of its molecular mechanisms in transgenic mice.

PMID- 9033287
TI  - Intestinal epithelial restitution. Involvement of specific laminin isoforms and
      integrin laminin receptors in wound closure of a transformed model epithelium.
AB  - Disruptions in the mucosal lining of the gastrointestinal tract reseal by
      epithelial cell migration, a process termed restitution. We examined the
      involvement of laminin isoforms and their integrin receptors in restitution using
      the intestinal epithelial cell line T84. T84 cells express primarily laminins 5,
      6, and 7 as indicated by immunostaining using laminin subunit-specific monoclonal
      antibodies (MAbs). A MAb (BM2) specific for the laminin alpha 3 subunit, a
      component of laminins 5, 6, and 7, completely inhibited the closure of mechanical
      wounds in T84 monolayers. Confocal microscopy using MAbs BM2 (laminin alpha 3
      subunit) and 6F12 (laminin beta 3 subunit) revealed that laminin-5 is deposited
      in a basal matrix that extends into the wound. The MAbs 4E10 (laminin beta 1
      subunit) and C4 (laminin beta 2 subunit) stained the lateral membranes between
      T84 cells. This staining was enhanced in cells adjoining wounds. Because T84
      cells stained faintly with MAbs 4C7 (laminin alpha 1 subunit) and with MAbs 4F11
      and 1B4 (laminin alpha 2 subunit), we suggest that expression of laminins 6 and 7
      is enhanced in response to wounding. The alpha 3 beta 1 integrin and the alpha 6
      containing integrins function in wound closure because MAbs specific for the beta
      1 integrin subunit (MAb13), the alpha 3 subunit (IVA5), and the alpha 6 subunit
      (2B7) potently inhibited T84 migration into wounds. Immunofluorescence using
      UMA9, a beta 4-integrin-specific MAb, revealed that alpha 6 beta 4 integrin
      exists in a Triton-X-100-insoluble structure at the basal surface and that the
      staining of this structure is enhanced in cells adjoining wounds. In addition, a
      Triton-X-100-soluble pool of alpha 6 beta 4, as well as alpha 3 beta 1 and
      presumably alpha 6 beta 1, was found along lateral surfaces of T84 cells. On
      flattened cells adjoining wounds, staining for these integrins was distributed
      diffusely, suggesting a redistribution that accompanies cell migration. Taken
      together, these data suggest that wound-induced epithelial cell migration is a
      finely tuned process that is dependent upon the regulated function and
      localization of specific laminins and their integrin receptors.

PMID- 9033290
TI  - Challenges for training thoracic surgeons in the future.

PMID- 9033291
TI  - The history of surgical procedures for emphysema.

PMID- 9033292
TI  - A national database for pulmonary surgery.

PMID- 9033293
TI  - Toward a new frontier in cardiac surgery.

PMID- 9033294
TI  - Surgical results and prognostic factors in early non-small cell lung cancer.
AB  - BACKGROUND: We attempted to clarify the prognostic value of tumor size (maximum,
      3 cm), the evidence of invasion proximal to a lobar bronchus at least 2 cm distal
      to the carina, and the absence or presence of visceral pleura invasion in
      patients with completely resected non-small cell lung carcinoma without lymph
      node invasion or satellite lesions (T1 N0 M0, T2 N0 M0). METHODS: The study
      included 158 patients. Four patients were excluded due to postoperative mortality
      (2.5%). The variables selected for the survival study were sex, age, symptoms
      presence or absence, bronchial invasion level (evidence or not of invasion
      proximal to a lobar bronchus at least 2 cm distal to the carina), pulmonary
      location, pneumonectomy or lesser resection, cell type, squamous or nonsquamous,
      tumor size, invasion or not of the visceral pleura, and T1 or T2 status. RESULTS:
      The overall survival rate in this series was 74% at 5 years and 60% at 10 years.
      Only the tumor size had a significant influence on survival (p = 0.0092).
      Patients with a tumor less than 2 cm in diameter did better (p = 0.0023).
      CONCLUSIONS: These observations suggest that it will be necessary to further
      research in clarifying the prognostic value of the bronchial invasion level and
      of the degree of the visceral pleura invasion and its implications when
      classifying a tumor as T1 or T2.

PMID- 9033295
TI  - Role of videothoracoscopy in chest trauma.
AB  - BACKGROUND: The aim of this study was to evaluate videothoracoscopic procedures
      in the setting of chest trauma. METHODS: We retrospectively analyzed our
      experience of videothoracoscopy in patients with either blunt trauma or
      penetrating thoracic injuries. RESULTS: Forty-three procedures involving 42
      patients were performed between July 1990 and April 1996. Indications for
      videothoracoscopy included suspected diaphragmatic injury (14 patients), clotted
      hemothorax (12), continued hemothorax (6), persistent pneumothorax (5),
      intrathoracic foreign body (4), posttraumatic chylothorax (1), and posttraumatic
      empyema (1 patient). Ten patients (24%) required conversion to thoracotomy. Two
      patients suffered postoperative pneumonia. There was one perioperative death.
      Mean hospital stay was 17 days; 21 days for patients with blunt trauma and 13
      days for patients with penetrating injuries. There was no procedure-related
      complication. Videothoracoscopy allowed precocious discharge of patients
      suffering penetrating injuries and allowed faster recovery in the majority of
      patients suffering severe blunt trauma. CONCLUSIONS: Videothoracoscopy appears to
      be a safe, accurate, and useful approach in selected patients with chest trauma.
      It is ideal for the assessment of diaphragmatic injuries, for control of chest
      wall bleeding, for early removal of clotted hemothorax, for treatment of empyema,
      for treatment of chylothorax, for treatment of persistent pneumothorax, and for
      removal of intrathoracic foreign body. However, we do not recommend the use of
      this technique in the setting of suspected great vessel or cardiac injury.

PMID- 9033296
TI  - Patterns of failure after trimodality therapy for malignant pleural mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma is uncommon, and presently, no
      standard treatment of this disease exists. The objective of our analysis was to
      study the patterns of failure for malignant pleural mesothelioma after
      trimodality treatment consisting of extrapleural pneumonectomy, chemotherapy, and
      radiation therapy. METHODS: Between 1987 and 1993, 49 patients with malignant
      pleural mesothelioma underwent extrapleural pneumonectomy. There were two
      perioperative deaths, and 1 patient died 5 weeks after extrapleural
      pneumonectomy. Thirty-five of the surviving patients received adjuvant
      chemotherapy (32/35 received cyclophosphamide, doxorubicin, and cisplatin)
      followed by hemithorax radiation therapy. Ten patients received chemotherapy but
      no radiation therapy, and 1 patient received no adjuvant therapy. Median follow
      up time for the 23 living patients from the date of operation was 18 months.
      RESULTS: Of the 46 evaluable patients, 25 had recurrence (54%), with a median
      time to first failure of 19 months (range, 5 to 51 months). The sites of first
      recurrence were local in 35% of patients, abdominal in 26%, the contralateral
      thorax in 17%, and other distant sites in 8%. (Some patients had recurrence in
      multiple sites simultaneously.) CONCLUSIONS: The most common site of failure
      after trimodality therapy was the ipsilateral hemithorax. Isolated distant
      failures were uncommon. Future strategies should investigate methods of enhancing
      local tumor control.

PMID- 9033297
TI  - Low-dose nitric oxide inhalation during initial reperfusion enhances rat lung
      graft function.
AB  - BACKGROUND: In ischemia-reperfusion injury, the production of nitric oxide by
      dysfunctional endothelium falls rapidly within minutes of the onset of
      reperfusion. Replenishment during this critical early period using inhaled nitric
      oxide may benefit lung grafts through modulation of vascular tone, endothelial
      permeability, neutrophil and platelet function, and availability of reactive
      oxygen species. METHODS: Rat lung grafts were flushed with 60 mL/kg cold
      University of Wisconsin solution and were reperfused either immediately (group I,
      n = 5) or after 24-hour 4 degrees C storage (groups II and III, n = 5 each), for
      60 minutes in an ex vivo model incorporating a support animal. Graft ventilation
      was with room air. In group III, 20 parts per million inhaled nitric oxide was
      added during the initial 10 minutes of reperfusion, whereas in groups I and II,
      equivalent flows of nitrogen were added to standardize oxygen concentration.
      RESULTS: Compared with group I, graft function in group II was poor, with
      reductions in oxygenation and blood flow and elevations of mean pulmonary artery
      pressure, peak airway pressure, and wet to dry weight ratio. In contrast, during
      nitric oxide inhalation in group III, graft function improved to control levels.
      This improvement was subsequently sustained throughout the reperfusion period.
      CONCLUSIONS: Low-dose inhaled nitric oxide administration in the early phase of
      reperfusion of stored lung grafts can yield sustained improvement in function.
      There may be a role for inhaled nitric oxide in the prevention of reperfusion
      injury in transplanted lungs.

PMID- 9033298
TI  - Successful transplantation of lungs topically cooled in the non-heart-beating
      donor for 6 hours.
AB  - BACKGROUND: The aim of this study was to transplant lungs that had been topically
      cooled in the non-heart-beating donor for 6 hours, using the most challenging
      evaluation method possible, namely single-lung transplantation followed by
      immediate contralateral pneumonectomy. METHODS: Domestic pigs were used (6 donors
      and 6 recipients) with a mean body weight of 59 +/- 3 kg. Ventricular
      fibrillation was induced, and after 1 minute, cardiac massage was started and
      heparin (5 mg/kg body weight) was given via a central venous catheter. Cardiac
      massage was continued for 10 minutes, during which the pig was ventilated with
      50% oxygen. The pleural cavities were opened and the tracheal tube disconnected
      from the ventilator, with the result that both lungs deflated. Saline slush was
      placed in both pleural cavities so that it completely covered the lungs. Within
      40 minutes the lung core temperature was less than 10 degrees C, and it was kept
      around 8 degrees C for 6 hours by adjusting the amounts of ice slush. The left
      lung was then harvested and transplanted into a prepared recipient, followed by
      right pneumonectomy within 46 +/- 4 minutes, thus making the recipient pig 100%
      dependent on the transplanted cadaver lung. RESULTS: The mean ischemic time for
      the cadaver lungs was 8 hours and 2 minutes (range, 7 hours and 25 minutes to 8
      hours and 59 minutes). All animals remained in excellent condition throughout the
      24-hour observation period, with arterial oxygen tensions of approximately 225 mm
      Hg, or 30 kPa (inspired oxygen fraction, 0.5). CONCLUSIONS: Lungs from non-heart
      beating donors may be used for transplantation if heparinization and topical
      cooling can be initiated within minutes of irreversible cardiac arrest.

PMID- 9033299
TI  - Gelatin-resorcinol-formaldehyde-glutaraldehyde glue-spread stapler prevents air
      leakage from the lung.
AB  - BACKGROUND: To reinforce the staple line of the emphysematous lung and thereby
      prevent air leakage during thoracoscopic operations, we have developed a
      procedure of lung excision that uses a gelatin-resorcinol-formaldehyde
      glutaraldehyde (GRFG) glue-spread stapler. METHODS: Formaldehyde-glutaraldehyde
      (FG) jelly is prepared by mixing FG fluid with 2.5% sodium carboxymethyl
      cellulose. The FG jelly is placed in the stapler groove and staple holes, and a
      gelatin-resorcinol (GR) mixture is applied. The GRFG glue-spread stapler was
      applied to emphysematous lung cutting during thoracoscopic operations in 10
      cases. RESULTS: An adhesion-strength test showed no difference in glue adhesion
      between FG fluid and FG jelly. An experiment using swine lung showed that with
      this newly developed stapler, no resistance in firing occurred, and GRFG glue
      covered every staple hole. Clinical application in 10 cases with emphysematous
      lung demonstrated no air leakage from the staple line, even long after the
      operation. CONCLUSIONS: Emphysematous lung excision using the GRFG glue-spread
      stapler during thoracoscopic operations is useful in preventing air leakage from
      the staple line and is a simple, safe, and low-cost procedure.

PMID- 9033300
TI  - Glucose control lowers the risk of wound infection in diabetics after open heart
      operations.
AB  - BACKGROUND: Elevated blood glucose levels in the postoperative period are
      associated with an increased risk of deep wound infection in diabetic individuals
      undergoing open heart operations at Providence St. Vincent Hospital. METHODS: Of
      8,910 patients who underwent cardiac operations between 1987 and 1993, 1,585
      (18%) were diabetic. The rate of deep sternal wound infections in diabetic
      patients was 1.7%, versus 0.4% for nondiabetics. Nine hundred ninety patients had
      their operation before implementation of the protocol and 595 after
      implementation. Charts of all diabetic patients were reviewed. Mean blood glucose
      levels were calculated from documented results of finger-stick glucometer
      testing. RESULTS: Thirty-three diabetic patients suffered 35 deep wound
      infections: 27 sternal (1.7%) and eight at the donor site (0.5%). Infected
      diabetic patients had a higher mean blood glucose level through the first 2
      postoperative days than noninfected patients (208 +/- 7.1 versus 190 +/- 0.8
      mg/dL; p < 0.003) and had a greater body mass index (31.5 +/- 1.4 versus 28.6 +/-
      0.1 kg/m2; p < 0.05). Multivariable logistic regression showed that mean blood
      glucose level for the first 2 days (p = 0.002), obesity (p < 0.002), and use of
      the internal mammary artery (p < 0.02) were all independent predictors of deep
      wound infection. Institution of a protocol of postoperative continuous
      intravenous insulin to maintain blood glucose level less than 200 mg/dL was begun
      in September 1991. This protocol resulted in a decrease in blood glucose levels
      for the first 2 postoperative days and a concomitant decrease in the proportion
      of patients with deep wound infections, from 2.4% (24/990) to 1.5% (9/595) (p <
      0.02). CONCLUSIONS: The incidence of deep wound infection in diabetic patients
      was reduced after implementation of a protocol to maintain mean blood glucose
      level less than 200 mg/dL in the immediate postoperative period.

PMID- 9033301
TI  - Hemodynamic performance of small aortic valve bioprostheses: is there a
      difference?
AB  - BACKGROUND: There is the potential for left ventricular outflow obstruction when
      small aortic valve bioprostheses are employed in normal-sized or large adults. It
      has been hoped that bovine pericardial valves would improve hemodynamic
      performance in the smaller tissue valve sizes. METHODS: To determine in vivo
      hemodynamic performance of heterograft aortic valve prostheses, we analyzed
      echocardiographic data from patients receiving 21- or 23-mm Carpentier-Edwards
      pericardial, Medtronic Intact, and Carpentier-Edwards porcine bioprostheses. In
      addition, data from 19-mm Carpentier-Edwards pericardial valves were included for
      comparison of hemodynamic performance between valve sizes. Doppler
      echocardiography was performed in 151 patients within 2 weeks of operation. Left
      ventricular outflow gradient was derived from continuous Doppler measurements of
      flow velocity, and effective orifice area was calculated by the continuity
      equation. RESULTS: There were statistically significant differences in
      hemodynamic performance of different sized prostheses for each valve type
      (effective orifice area, p < 0.01; valvular gradient, p < 0.03). There were,
      however, no significant differences in effective orifice area or mean gradient
      for different valve types within each size category. CONCLUSIONS: The in vivo
      hemodynamic performance of these three different aortic valve heterograft
      bioprostheses is similar. Patient-prosthesis mismatch with heterograft
      prostheses, as demonstrated by the indexed effective orifice area can be avoided
      by appropriate sizing and use of annular enlarging techniques when necessary.

PMID- 9033302
TI  - Development of an implantable ventricular assist system.
AB  - BACKGROUND: This study describes the present state of progress in the development
      of the Jarvik 2000 ventricular assist system. METHODS: Designed for implantation
      in the human thorax, the system consists of a small (25 cm3, 90 g)
      intraventricular axial-flow blood pump that transmits power and data via internal
      electronics and a transcutaneous energy transfer system. The pump is powered by
      portable internal and external polymer lithium ion batteries. The only moving
      part, the pump rotor, contains a permanent magnet of a brushless direct-current
      motor that mounts an axial-flow impeller and partial magnetic thrust support,
      with blood-immersed radial and thrust bearings. The motor uses a redundant coil
      and electric lead design, which permits continued operation in case of wire
      breakage. RESULTS: Seven calves have been supported for an average of 107 days
      (range, 40 to 162 days) with prototypes of the Jarvik 2000 ventricular assist
      system. No physiologic complications have occurred. When its user is at rest, the
      pump produces flows of 5 to 6 L/min with a decreased arterial pulse contour.
      Renal and hepatic functions have remained normal throughout the duration of all
      studies. Mean plasma free hemoglobin levels ranged from 4.3 to 11.4 mg/dL (mean,
      6.3 mg/dL) for each study. Pathologic analyses of the heart and kidneys revealed
      no damage related to the device. CONCLUSIONS: These studies indicate that the
      Jarvik 2000 ventricular assist system is feasible in animals and holds promise
      for long-term support of patients.

PMID- 9033303
TI  - Sequential venous bypass grafts: results 10 years later.
AB  - BACKGROUND: To evaluate the long-term outcome of the sequential vein bypass
      grafting technique, we studied 92 patients with coronary artery disease
      undergoing coronary artery bypass grafting in 1984 by one surgeon and receiving
      at least one sequential vein bypass graft (total of 170 sequential bypass
      grafts). METHODS: There was one hospital death and 1 patient was lost to follow
      up. The remaining 90 patients were followed up by clinical evaluation, and 80% of
      the patients underwent coronary angiography within 1 year from the end point of
      the follow-up (June 1995), or before recurrence of symptoms or death. RESULTS:
      All patients except 3 had improvement of their angina class (Canadian
      Cardiovascular Society) at the end of the follow-up. Twelve patients did not have
      improvement of their New York Heart Association functional class postoperatively,
      but only 1 deteriorated. The mean left ventricular ejection fraction remained
      unchanged at the end of the follow-up period, and ergometry results were
      satisfactory during the follow-up period. The 10-year survival rate was 74%, and
      the cardiac event-free survival rate was 72%. Only 37% of the deaths occurring
      during the follow-up were cardiac-related deaths. In 56 patients with
      angiographic routine control 9 to 10 years postoperatively, 76 of 89 sequential
      vein grafts were found patent. CONCLUSIONS: It is thought that the optimal long
      term results of sequential bypass grafts may be dependent on where the terminal
      anastomosis of the sequence (the end-to-side anastomosis) is placed. The
      technique of sequential grafting with the reversed saphenous vein is easier to
      employ than the single grafting technique, and in the present study has been
      demonstrated to have good long-term results. Furthermore, it allows for a more
      complete revascularization of the myocardium, which is particularly important in
      patients with diffuse coronary artery disease.

PMID- 9033304
TI  - Diagnosis and operation for anomalous circumflex coronary artery.
AB  - BACKGROUND: Origin of the left circumflex coronary artery from the right sinus of
      Valsalva is the most common anatomic variation of the coronary artery
      circulation. However, there are few reports about the operative approach to this
      anomalous vessel. METHODS: Forty patients having this anomaly were identified
      from 10,216 adult cardiac catheterization procedures. Forty percent of the
      anomalous circumflex coronary arteries (ACCAs) had critical atherosclerotic
      lesions. Eighty cases needed bypass grafting. RESULTS: For diagnosis of ACCA, the
      aortic root sign was positive in 94.9% of the diagnosed patients and the
      nonperfused myocardium sign was found in 92.5%. Eighty percent of ACCAs were
      larger than 2 mm in radiographic diameter before their passage into the
      atrioventricular groove. However, after emerging from the atrioventricular
      groove, 70% measured less than 1.5 mm. Consequently, a technique was developed to
      bypass the proximal ACCA and was used in 2 cases. Six other patients with more
      distal disease and larger vessels underwent conventional bypass grafting.
      CONCLUSIONS: The aortic root sign and nonperfused myocardium are useful in
      diagnosing ACCA. The ACCA is usually too small for use of the conventional graft
      technique. Therefore, a technique was developed to graft more proximally and was
      applied successfully in 2 cases.

PMID- 9033306
TI  - Effects of butanedione monoxime and temperature on prolonged cardiac storage.
AB  - BACKGROUND: The optimal temperature for cardiac allograft storage remains
      controversial. We conjectured that supplementation of the potent cardioprotective
      agent 2,3-butanedione monoxime with calcium may improve allograft storage and
      make the precise storage temperature less critical. METHODS: Hearts were
      harvested from Sprague-Dawley rats (250 to 350 g), mounted on a Langendorff
      apparatus, and instrumented with an intraventricular balloon. Hearts were flushed
      and stored with either unmodified University of Wisconsin solution (UWS) or UWS
      supplemented with 10 mmol/L of 2,3-butanedione monoxime and calcium 0.1 mmol/L
      (BDM). Hearts were then subjected to 12 hours of storage at one of five
      temperatures (0 degree, 4 degrees, 8 degrees, 12 degrees, or 16 degrees C) in a
      complete 2 x 5 factorial design (n = 6/group). Data are reported either as a
      percentage of the prestorage results or as an absolute value (mean +/- standard
      deviation). RESULTS: Recovery of developed pressure (p < 0.0001), coronary flow
      (p < 0.0001), and diastolic volume (p < 0.001) were significantly enhanced,
      whereas creatine kinase (p < 0.0001) and lactate dehydrogenase release (p <
      0.0001) were reduced in the BDM versus the UWS groups. In both the BDM and UWS
      storage groups, recovery was better at temperatures of 8 degrees C or less than
      at 12 degrees C or more. The single preferred temperature was 4 degrees C,
      significantly better than 0 degree C with unmodified UWS, while similar to 0
      degree and 8 degrees C with BDM. Adenine nucleotide values were decreased equally
      in the BDM and UWS hearts, but preservation was enhanced at 0 degree C compared
      with all warmer temperatures. CONCLUSIONS: We conclude that 4 degrees C is the
      preferred temperature for prolonged cardiac storage with UWS and that the
      inclusion of 2,3-butanedione monoxime with calcium 0.1 mmol/L markedly enhances
      recovery for storage temperatures of 8 degrees C or less.

PMID- 9033305
TI  - High-dose isosorbide dinitrate for myocardial revascularization with composite
      arterial grafts.
AB  - BACKGROUND: Composite arterial grafting for myocardial revascularization is a
      surgical technique in which free arterial conduits are proximally attached to an
      in situ internal mammary artery. METHODS: Composite arterial grafting was
      performed in 78 patients with internal mammary artery (n = 24), inferior
      epigastric artery (n = 21), or radial artery (n = 33) connected to the internal
      mammary artery. Overall, 254 distal anastomoses were performed (average number,
      3.3 per patient), 225 of which were arterial. All patients were treated
      postoperatively with high-dose isosorbide dinitrate (4 to 20 mg/h for 24 hours).
      RESULTS: The in-hospital mortality rate was 2.6% (2 patients). Early
      recatheterization studies performed 3 weeks (range, 1 to 20 weeks) after
      operation in 30 patients demonstrated patency rates of 100%, 93%, and 100% for
      the composite internal mammary artery, inferior epigastric artery, and radial
      artery groups, respectively. In addition, two inferior epigastric artery conduits
      had major intraluminal constriction. At a mean follow-up of 20 months (range, 1
      to 42 months) all patients are alive, and all but 2 in the inferior epigastric
      group (97%) are angina free. CONCLUSIONS: This surgical technique can be safely
      used. On the basis of our experience, the right internal mammary artery and the
      radial artery are the most suitable conduits for this procedure. High-dose
      nitrates given perioperatively prevent spasm and ensure early patency rates.

PMID- 9033307
TI  - Coagulase-negative staphylococcal sternal wound infections after open heart
      operations.
AB  - BACKGROUND: Coagulase-negative staphylococci are commonly isolated from wounds of
      patients after median sternotomy; however, the epidemiology of these infections
      is poorly described and the morbidity, mortality, and cost of care remain
      undefined. METHODS: Retrospectively, we studied all patients with sternal wound
      infections attributable to coagulase-negative staphylococci after 22,180 open
      heart procedures performed at the Cleveland Clinic between January 1, 1988, and
      December 31, 1994 (84 months). In an assessment of potential risk factors for
      sternal wound infections caused by coagulase-negative staphylococci, 17 patients
      with coagulase-negative staphylococcal sternal wound infections were compared
      with 29 patients who underwent open heart operations without subsequent sternal
      wound infections, as well as with another 22 patients in whom sternal wound
      infections attributable to other pathogens developed. RESULTS: A total of 436
      sternal wound infections were identified (19 per 1,000 procedures), of which 100
      (23%) were attributable to coagulase-negative staphylococci (4.5 per 1,000).
      Fifty-six percent of coagulase-negative staphylococcal sternal wound infections
      were superficial, 27% were deep, and 17% represented mediastinitis; 14% of
      patients had a concomitant secondary bloodstream infection. Ninety-two percent of
      coagulase-negative staphylococcal isolates were methicillin resistant. The mean
      interval from operation to onset of infection was 24 days (range, 4 to 388 days),
      and most patients had purulent discharge from the chest wound, fever, and
      leukocytosis. Adverse outcomes included reexploration (39%), flap operation
      (12%), and sternectomy (5%); 89% required parenteral antibiotics for a mean of 22
      days. This resulted in 2,600 additional hospital days, with an average additional
      direct cost per case of $20,000. In both case-control studies, insulin-dependent
      diabetes mellitus was the only risk factor significantly associated with sternal
      wound infections attributable to coagulase-negative staphylococci (p value = 0.02
      by two-tailed Fisher's exact test). CONCLUSIONS: Sternal wound infections
      attributable to coagulase-negative staphylococci had a substantial impact on
      cardiothoracic surgery-related morbidity.

PMID- 9033308
TI  - Oral disease burden in patients undergoing prosthetic heart valve implantation.
AB  - BACKGROUND: Valvular heart disease predisposing to endocarditis and requiring
      prosthetic valve implantation is common among the elderly. Spontaneous
      bacteremias associated with acute or chronic oral/odontogenic infections may
      represent a far greater cumulative risk for the development of endocarditis than
      do occasional health care procedures administered in a professional setting.
      METHODS: To determine the oral disease burden in patients undergoing mechanical
      or bioprosthetic heart valve implantation, we performed a comprehensive clinical
      and radiographic regional examination on 156 consecutive patients, with emphasis
      on identifying acute and chronic oral/odontogenic infections and conditions.
      RESULTS: The mean number of remaining teeth in the cohort was 19.32; of these,
      1.07 were carious, involving a mean number of 2.51 tooth surfaces. In addition,
      15.38% of the patients had evidence of acute or chronic periapical abscesses, and
      43.6% of the patients had moderate to advanced periodontitis. CONCLUSIONS: In
      view of the substantial morbidity and mortality associated with prosthetic valve
      endocarditis and based upon the high incidence of dental disease identified in
      patients undergoing valvular operations, routine preoperative dental assessment
      should be deemed a "medical necessity" by third-party payors. Appropriate
      therapeutic intervention should be initiated whenever possible before valve
      implantation.

PMID- 9033309
TI  - Reoperative coronary bypass grafting without cardiopulmonary bypass through a
      small thoracotomy.
AB  - BACKGROUND: The danger of coronary reoperations is mainly hidden in the reopening
      of the sternum and in the manipulation of the heart and the old grafts.
      Therefore, the minimally invasive direct coronary artery bypass procedure seems
      an ideal technique for coronary reoperations if only the left anterior descending
      coronary artery needs to be revascularized and the left internal mammary artery
      has not been used previously. METHOD: From January 1995 until May 1996 we
      performed 81 minimally invasive direct coronary artery bypass procedures through
      a small anterolateral thoracotomy in the fifth intercostal space, anastomosing
      the left internal mammary artery to the left anterior descending coronary artery.
      Six of these 81 were reoperative minimally invasive direct coronary artery bypass
      procedures on patients who had previously undergone coronary grafting through a
      median sternotomy with a vein graft to the left anterior descending coronary
      artery. RESULTS: Mean operation time was 85.8 +/- 22.2 minutes. Mean length of
      the mammary pedicles was 13 +/- 2 cm. Mean coronary occlusion time was 9.2 +/-
      3.2 minutes. Mean postoperative hospital stay was 5.7 +/- 1.2 days (range, 5 to 8
      days). No mortality and no cardiac-related morbidity were recorded. CONCLUSIONS:
      These results suggest that the technique is safe and promising in selected cases
      of reoperative coronary operation.

PMID- 9033310
TI  - Addition of calcium to Euro-Collins solution is essential for 24-hour
      preservation of the vasculature.
AB  - BACKGROUND: Genuine Euro-Collins solution is calcium free. The aim of this study
      was to investigate whether the addition of calcium would improve its capacity to
      preserve the vasculature. METHODS: The infrarenal aorta of Sprague-Dawley rats
      was investigated in organ baths: as fresh controls, after 24 hours of cold (4
      degrees C) storage in Euro-Collins solution, or in Euro-Collins solution with the
      addition of calcium in amounts ranging from 0.05 to 1.5 mmol/L. The thromboxane
      analogue U-46619 was used to investigate contractility. Endothelium-dependent
      relaxation was tested by cumulative addition of acetylcholine. Papaverine was
      used to elicit endothelium-independent relaxation. Investigation by transmission
      electron microscopy was also performed. RESULTS: Storage of rat aorta for 24
      hours in genuine Euro-Collins solution almost abolished smooth muscle function,
      and severe edema was found in the endothelial cells. However, if calcium was
      added, the rat aorta could be stored for 24 hours without affecting smooth muscle
      function, and endothelium-dependent relaxation was only slightly reduced.
      Furthermore, only slight edema could be demonstrated in the endothelial cells.
      CONCLUSIONS: If calcium is added to Euro-Collins solution in amounts ranging from
      0.4 to 1.5 mmol/L, it allows good preservation of rat aorta for 24 hours. Without
      calcium, this solution destroys both the function and morphology of the vessels.

PMID- 9033311
TI  - Nitric oxide dose response during moderate and severe hypoxia in swine.
AB  - BACKGROUND: Elucidation of factors that influence the dose response to inhaled
      nitric oxide is crucial to optimizing its therapeutic benefit. We investigated
      whether severity of hypoxia is one such factor. METHODS: Seven Yorkshire swine
      underwent 14 triphasic experiments: (1) control period of mechanical ventilation
      (fractional concentration of oxygen = 0.3); (2) induction of hypoxic pulmonary
      hypertension (fractional concentration of oxygen = 0.1 to 0.15); and (3) inhaled
      nitric oxide at 5, 10, 20, 40, and 80 parts per million (ppm). Hemodynamics and
      arterial blood gases were measured by pulmonary and systemic arterial catheters.
      RESULTS: Experiments were divided into two groups of seven based on hypoxia
      severity: severe (arterial oxygen tension, 25 to 40 mm Hg) and moderate (arterial
      oxygen tension, 41 to 60 mm Hg). The percent changes in mean pulmonary artery
      pressure after each dose were compared within each group by repeated measure
      analysis of variance and each dose was compared between the two groups by
      Student's t test. A statistically significant dose response existed in both
      groups (p < 0.02). Low doses resulted in significantly less vasodilation in the
      severe versus the moderate hypoxia group (5 ppm, 59% +/- 6% versus 94% +/- 7%, p
      = 0.003; 10 ppm, 69% +/- 8% versus 99% +/- 8%, p = 0.017). CONCLUSIONS: Lower
      doses are significantly less effective in achieving maximal pulmonary
      vasodilation during severe hypoxia. Therefore, the degree of hypoxia is a
      determinant of the inhaled nitric oxide dose response.

PMID- 9033312
TI  - Intraluminal shunt for the thoracic aorta: blood flow and function in chronic
      studies.
AB  - BACKGROUND: Aortic cross-clamping during operations on the thoracic aorta may
      result in paraplegia or kidney failure. METHODS: A nonshunting method of repair
      was compared with intraluminal shunting in two groups of young pigs: the no-shunt
      group, which received simple aortic cross-clamping at the ligamentum for 15
      minutes; and the shunt group, which received an aortic graft with a temporary
      intraluminal shunt and balloon occlusion of the inferior vena cava only during
      shunt insertion and removal. Blood flow to the spinal cord and viscera was
      measured with radiolabeled microspheres on days 1, 3, 5, and 7 after operation.
      Renal and neurologic function and histology also were studied. RESULTS: In the no
      shunt group, there was hyperemia of the lumbar cord compared with the shunt
      group. There were no significant differences in renal cortex blood flow or
      creatinine clearance. Seven of 10 animals in the no-shunt group had paraplegia,
      compared with none in the shunt group. Histologic studies of the lower lumbar
      cord showed bilateral central necrosis of gray matter in the no-shunt group, but
      no evidence of necrosis in the shunt group. CONCLUSIONS: An intraluminal shunt
      allowed thoracic aorta reconstruction without paraplegia.

PMID- 9033313
TI  - Allograft root on closed pulmonary valve for subaortic obstruction in double
      inlet left ventricle with transposition of the great arteries.
AB  - BACKGROUND: Until recently closure of the pulmonary valve during staged Fontan
      type palliation in the setting of double-inlet left ventricle with an
      unrestrictive or adequately enlarged ventricular septal defect and transposition
      of the great arteries with the aorta on a left-sided outflow chamber was regarded
      as an appropriate part of surgical treatment. Lately, however, an increased
      incidence of subsequent subaortic obstruction has been described in this regard.
      METHODS: Allograft root placement on the previously closed pulmonary orifice in
      combination with a modified Damus-Kaye-Stansel procedure is described to create
      an unobstructed outflow from the main ventricle to the systemic circulation. This
      procedure was done in 3 patients. One root placement was combined with the
      construction of the bidirectional superior cavopulmonary connection, one was done
      as an intermediate step before completion of the cavopulmonary connection, and
      one was combined with completion of total cavopulmonary connection. RESULTS:
      Immediate relief of the subaortic obstruction was achieved in all 3 patients.
      Ventricular hypertrophy, echocardiographically assessed by diastolic posterior
      wall thickness, regressed to normal in all 3 within 6 to 12 months. CONCLUSIONS:
      Allograft root placement on the reopened pulmonary orifice in double-inlet left
      ventricle with a ventricular septal defect and transposition of the great
      arteries appears technically feasible and functionally adequate on short-term
      follow-up. This procedure should result in regression of ventricular hypertrophy
      to allow eligibility for a Fontan-type palliation again. To what extent possible
      failure of the allograft increases the risk of an adverse outcome of this
      palliation may be a matter of concern.

PMID- 9033314
TI  - Surgical preparation abolishes endothelium-derived hyperpolarizing factor
      mediated hyperpolarization in the human saphenous vein.
AB  - BACKGROUND: The impairment of the synthesis and release of endothelium-derived
      relaxing factors may be related to the high incidence of atherosclerosis and
      occlusion in saphenous vein grafts. This study focused on the effect of surgical
      preparation on one of the endothelium-derived relaxing factors, endothelium
      derived hyperpolarizing factor, in the human saphenous vein. METHODS: Human
      saphenous vein segments taken from patients undergoing coronary bypass were
      placed in an organ bath. A glass microelectrode was inserted into a smooth muscle
      cell. The membrane potential in response to acetylcholine (-9 to -5 log M) was
      measured in normal or surgically prepared saphenous vein with presence or absence
      of NG-nitro-L-arginine (300 mumol/L) and indomethacin (7 mumol/L). RESULTS: The
      resting membrane potential was -71.28 +/- 1.91 mV (n = 7) with intact endothelium
      and -65.5 +/- 2.92 mV (n = 6, p > 0.05) without endothelium. Acetylcholine
      hyperpolarized membrane potential with intact endothelium (-90.57 +/- 1.48 mV, n
      = 7, p < 0.001), but not without endothelium (-69.67 +/- 2.93 mV, n = 6, p >
      0.05). In the surgically prepared saphenous vein, acetylcholine did not
      hyperpolarize membrane potential (-71.83 +/- 3.84 mV versus the resting membrane
      potential of -69.50 +/- 3.53 mV, n = 6, p > 0.05). CONCLUSIONS: The endothelium
      derived hyperpolarizing factor plays a role in the human saphenous vein. The
      surgical preparation abolishes the endothelium-derived hyperpolarizing factor
      mediated hyperpolarization in the saphenous vein. This study provides evidence of
      functional changes of endothelium by traditional surgical preparation from
      another point of view, and it may be related to the high incidence of occlusion
      in saphenous vein grafts.

PMID- 9033317
TI  - Intraoperative ultrasonographic troubleshooting after the arterial switch
      operation.
AB  - BACKGROUND: Less than perfect coronary artery translocation accounts for the
      majority of perioperative deaths after the arterial switch procedure for
      transposition of the great arteries. Some types of coronary arterial anatomy are
      associated with a higher risk of death. METHODS: Prospective epicardial
      ultrasound examination of all neonates with failing left ventricle or difficulty
      in weaning off cardiopulmonary bypass was performed after completion of the
      arterial switch operation during a 2-year period from March 1994 to February
      1996. The aim was to identify any mechanical, and potentially remediable, factors
      accounting for ventricular failure. RESULTS: Four neonates fulfilling the above
      criteria were identified during a 2-year period when epicardial echocardiography
      was routinely applied. In 2 patients coronary arterial problems in the form of
      kinking of the proximal left coronary artery (1 patient) and extrinsic
      compression of the artery by the neo-pulmonary trunk (1 patient) were identified
      and successfully corrected. In 2 other patients, supravalvar aortic stenosis was
      recognized, leading to prompt revision. CONCLUSIONS: Epicardial echocardiography
      has an important "troubleshooting" role in the subgroup of patients with a
      suboptimal hemodynamic result after the arterial switch operation. Patients with
      unusual coronary anatomy should routinely be candidates for such studies.

PMID- 9033315
TI  - The role of surgical ligation of patent ductus arteriosus in the era of the
      Rashkind device.
AB  - BACKGROUND: The role of surgery in managing patent ductus arteriosus (PDA) was
      studied in the era of the Rashkind double-umbrella device. METHODS: All 354
      patients with PDA referred to our center in a 5-year period were included in this
      report. Of the 354 patients, 236 underwent cardiac catheterization with the
      intent of transcatheter PDA closure, and 118 had surgical intervention. RESULTS:
      In 46 (19.5%) of the 236 patients having cardiac catheterization, the procedure
      either was abandoned or failed. Color Doppler echocardiography demonstrated total
      occlusion of the ductus after 24 hours in 97 patients (41%) in the cardiac
      catheterization group. An additional 20 patients had no residual leaks at follow
      up. Twenty other patients underwent reocclusion because of a residual shunt.
      Thus, of the 236 patients, 137 (58%) had successful complete closure of the PDA.
      Surgical PDA ligation was performed in 118 patients as the initial procedure and
      in 26 of the 46 patients in whom transcatheter closure was abandoned. If the
      remaining 20 patients in whom transcatheter closure failed are added to the 144
      patients who underwent PDA ligation, the percentage having surgical intervention
      versus transcatheter occlusion is higher than 46%. CONCLUSIONS: Our data suggest
      that surgery plays a major role in the management of patients with PDA despite
      the advent of new interventional catheterization techniques.

PMID- 9033316
TI  - Cardiopulmonary bypass with heparin-coated circuits and reduced systemic
      anticoagulation.
AB  - BACKGROUND: The improved biocompatibility of the cardiopulmonary bypass circuits
      made possible by the use of surface-immobilized heparin may allow for a reduction
      in the amount of heparin administered systemically. This study was performed to
      elucidate the effects of cardiopulmonary bypass using heparin-coated circuits and
      reduced heparinization on hemostatic variables and clinical outcome. METHODS:
      Thirty patients scheduled to undergo myocardial revascularization were randomized
      to have either a heparin-coated or an uncoated cardiopulmonary bypass circuit.
      Anticoagulation was induced with heparin (100 IU/kg in the coated group and 300
      IU/kg in the uncoated group) and the activated clotting time was kept over 200
      and 480 seconds in the coated and uncoated groups, respectively. RESULTS: The
      postoperative overnight loss of hemoglobin through the drains was lower in the
      heparin-coated group (43.6 g; range, 18.5-69.0 g) than in the uncoated group
      (73.0 g; range, 32.2-137.7 g) (p = 0.0015). Plasma concentrations of prothrombin
      fragment 1 + 2 and D-dimer were significantly more elevated after cardiopulmonary
      bypass in the coated group than they were in the uncoated group. Two patients in
      the coated group had a stroke postoperatively. CONCLUSIONS: The reduction in
      systemic heparinization was associated with thrombin formation, which may
      predispose to intravascular and cardiopulmonary bypass circuit clotting.
      Therefore, generous systemic heparinization may still be prudent despite the
      improved biocompatibility offered by heparin-coated surface.

PMID- 9033318
TI  - Functional and metabolic effects of adenosine in cardioplegia: role of
      temperature and concentration.
AB  - BACKGROUND: Addition of adenosine to cardioplegic fluid has been shown to improve
      myocardial tolerance to ischemia. This study was designed to investigate further
      this phenomenon to evaluate the dose-response and the temperature dependence of
      the effect of addition of adenosine to St. Thomas' Hospital cardioplegic
      solution. METHODS: The isolated working rat heart model was used in this study.
      After the assessment of control function, hearts (6 in each group) were subjected
      to infusions of cardioplegic solution containing 0.0 (control), 0.1, 5.0, 10.0 or
      20.0 mmol/L adenosine followed by 3 hours of ischemic arrest at temperatures of
      20 degrees C, 10 degrees C, or 4 degrees C with multidose (3 minutes every 30
      minutes) cardioplegic infusion. RESULTS: After ischemic arrest at 20 degrees C,
      the recovery of cardiac output (expressed as percent of preischemic baseline) was
      35.4 +/- 5.11 (control) 45.0 +/- 5.51 (0.1 mmol/L), 53.1 +/- 2.9 (5.0 mmol/L),
      61.8 +/- 3.7 (10.0 mmol/L), and 57.6 +/- 2.3 (20.0 mmol/L). Hearts receiving 5.0
      to 20.0 mmol/L adenosine had significantly greater recovery of cardiac output
      than control hearts. In its optimal concentration (10 mmol/L), adenosine improved
      the efficacy of the cardioplegic solution by almost 75%. Myocardial adenosine
      triphosphate content (expressed in mumol/g protein) was 4.7 +/- 0.5 (control),
      4.9 +/- 1.4 (0.1 mmol/L), 8.1 +/- 0.7 (5 mmol/L), 12.5 +/- 2.0 (10 mmol/L), and
      11.2 +/- 2.8 (20 mmol/L), at the end of ischemia and 13.9 +/- 0.2 (control), 13.1
      +/- 1.7 (0.1 mmol/L), 18.0 +/- 2.0 (5 mmol/L), 18.6 +/- 1.2 (10 mmol/L), and 20.7
      +/- 2.1 (20 mmol/L) at the end of reperfusion. Thus, the adenosine triphosphate
      content was higher (p < 0.05) in hearts receiving 5.0 to 20.0 mmol/L adenosine
      than in controls both at the end of ischemia and after reperfusion. Myocardial
      adenosine monophosphate level at the end of ischemia was inversely related to
      adenosine triphosphate level. Functional assessment of the effect of 10 mmol/L
      adenosine at 10 degrees C and 4 degrees C during arrest indicated attenuation of
      beneficial effects: adenosine improved function only by 17% at 10 degrees C,
      whereas at 4 degrees C the protective effect was not observed. CONCLUSIONS: These
      observations suggest that adenosine has the potential to enhance the efficacy of
      clinical cardioplegic arrest but the degree of improvement is lower at decreased
      temperature during ischemia. A principal mechanism of action of this modification
      of cardioplegic fluid appears to be through the inhibition of high-energy
      phosphate utilization immediately before or during ischemia.

PMID- 9033319
TI  - Use of an adjustable tourniquet to reverse cyanosis in the newborn pig.
AB  - BACKGROUND: Previous surgical models of cyanosis have been permanent. Because
      normal oxygenation was not restored in these models, it is unclear whether the
      metabolic changes produced by prolonged exposure to hypoxemia are irreversible.
      We therefore designed an experimental model of cyanosis that is reversible.
      METHODS: The left atrial appendage was anastomosed directly to the main pulmonary
      artery in 8 piglets, aged 2 to 4 weeks. RESULTS: The oxygen saturation fell from
      95.3% +/- 0.8% to 72.4% +/- 3.9% (p < 0.001). A tourniquet was placed around the
      anastomosis to produce incremental changes in the level of cyanosis. Complete
      tourniquet occlusion resulted in obliteration of the right to left shunt, with
      return of systemic oxygen saturation to baseline levels. Systemic, left atrial,
      and pulmonary pressures did not change during the study. CONCLUSIONS: In this
      acute preparation, stable hemodynamic conditions were maintained despite
      substantial variations in systemic levels of oxygenation. Most important, this
      model allows reversal of cyanosis with the return of normal oxygenation.
      Application of this experimental design in a chronic model may help to determine
      whether the metabolic effects of prolonged hypoxemia are potentially reversible.

PMID- 9033321
TI  - Aortic valve repair of congenital stenosis with bovine pericardium.
AB  - BACKGROUND: Conservative surgical options in the treatment of congenital aortic
      stenosis are limited. To relieve the obstruction necessitates full incision of
      the raphe of the larger valve leaflet, but this inevitably causes prolapse.
      METHODS: We performed aortic valve repair in 6 children, aged 14 months to 17
      years, with congenital aortic stenosis, 2 having had aortic valvotomy as infants.
      The repair consisted of suturing the base of a triangular piece of bovine
      pericardium, with a simple vertical fold, to the free edges of the incised raphe.
      The pericardial fold was then sutured vertically to the aortic wall. RESULTS: At
      follow-up of 2 to 60 months, the mean peak systolic Doppler gradients had
      decreased from 80 +/- 15 mm Hg to 26 +/- 9 mm Hg. The effective valvular orifice
      area increased from 33% +/- 6% to 64% +/- 3%, allowing blood flow to increase by
      a factor of 3.76. Two patients have mild and 2 have mild-to-moderate aortic
      regurgitation. CONCLUSIONS: The described conservative repair renders the valve
      tricuspid and trisinusoidal, and the deficient interleaflet triangle is
      recreated, preventing cusp prolapse. Longer follow-up is required to assess the
      durability of unstented pericardium in the aortic position, but the early results
      are encouraging.

PMID- 9033320
TI  - Beneficial effects of fluosol-polyethylene glycol cardioplegia on cold, preserved
      rabbit heart.
AB  - BACKGROUND: Because of its high oxygen-carrying capacity, especially at low
      temperatures, fluosol may enhance heart preservation. METHODS: Hearts of male New
      Zealand white rabbits (1.5-2.0 kg) were excised and flushed through the aorta
      with 0 degree C St. Thomas' Hospital solution, fluosol, or polyethylene glycol or
      fluosol-polyethylene glycol cardioplegic solution. Hearts were then stored for 12
      hours at 0 degree C and reperfused with Krebs-Henseleit buffer at 36.5 degrees C
      for 60 minutes using a Langendorff system. RESULTS: Myocardial contractile
      function was significantly greater in the fluosol-polyethylene glycol
      cardioplegia-preserved group (p < 0.01) and polyethylene glycol-cardioplegia
      preserved group (p < 0.05) than in the St. Thomas' Hospital solution-preserved
      group. The myocardial high-energy phosphate content was significantly higher in
      the fluosol-polyethylene glycol-cardioplegia-preserved group (p < 0.01), with
      reduced release of lactate dehydrogenase (p < 0.01) in comparison with the St.
      Thomas' Hospital solution-preserved group. CONCLUSIONS: The addition of fluosol
      and polyethylene glycol to the cardioplegic solution may enhance long-term cold
      heart preservation.

PMID- 9033323
TI  - Thoracoscopic cardiomyoplasty: a canine feasibility study.
AB  - BACKGROUND: Thoracoscopy may be effective in reducing the surgical stress of
      cardiomyoplasty. The feasibility of thoracoscopy in cardiomyoplasty was
      investigated. METHODS: Cardiomyoplasty by thoracoscopy and by the open method
      through a thoracotomy was performed in dogs. After 8 to 10 weeks of
      preconditioning, the hemodynamic effect of burst stimulation was measured.
      RESULTS: Cardiomyoplasty by thoracoscopy took 90 +/- 21 minutes (mean +/-
      standard deviation), whereas cardiomyoplasty by the open method took 67 +/- 10
      minutes (p < 0.05). As a result of burst stimulation, aortic pressure, descending
      aortic flow, and left atrial pressure increased by 15.1% +/- 6.5%, 8.6% +/- 6.3%,
      and 3.8% +/- 4.6%, respectively, in the dogs that received the cardiomyoplasty by
      thoracoscopy, whereas those indices increased by 16.5% +/- 6.9%, 9.8% +/- 5.9%,
      and 4.8% +/- 4.2%, respectively, in dogs that received cardiomyoplasty by the
      open method. No significant difference between the two groups was shown in any
      index. CONCLUSIONS: Cardiomyoplasty by thoracoscopy was technically practical,
      and its hemodynamic effect was similar to that of the open method. The
      feasibility of cardiomyoplasty by thoracoscopy was thereby suggested.

PMID- 9033322
TI  - Nitric oxide synthase and adenylyl and guanylyl cyclase activity in porcine
      interposition vein grafts.
AB  - BACKGROUND: A high proportion of autologous saphenous vein grafts occlude as the
      result of intimal thickening. Blood vessels synthesize substances that may
      inhibit such intimal thickening. These include cyclic adenosine monophosphate
      (cAMP) and cyclic guanosine monophosphate (cGMP), which are stimulated by
      prostacyclin and nitric oxide, respectively. The prostacyclin-cAMP and nitric
      oxide-cGMP axes were therefore investigated in porcine vein grafts. METHODS:
      Saphenous vein-carotid artery interposition graft procedures were carried out in
      pigs. One month after the operation, ungrafted saphenous veins, vein grafts, and
      carotid arteries were excised, the formation of cAMP and cGMP was assessed by
      radioimmunoassay, and the nitric oxide synthase content was determined by
      autoradiography. RESULTS: The formation of cAMP and nitroprusside-stimulated cGMP
      was significantly diminished in vein grafts compared with ungrafted saphenous
      veins and carotid arteries. Calimycin-stimulated cGMP synthesis (nitric oxide
      release dependent) and the endothelial nitric oxide synthase content
      (autoradiography) were significantly elevated in vein grafts compared with
      ungrafted saphenous veins but were significantly less than those in carotid
      arteries. CONCLUSIONS: Adenylyl and guanylyl cyclase activity are down-regulated
      in vein grafts, which may contribute to the development of intimal and medial
      thickening. Nitric oxide release and endothelial nitric oxide synthase content
      are up-regulated in vein grafts, which is indicative of an adaptation to the
      arterial conditions of shear stress and pulsatile pressure.

PMID- 9033324
TI  - Effect of heparin loading during congenital heart operation on thrombin
      generation and blood loss.
AB  - BACKGROUND: The heparin protocols used during cardiopulmonary bypass (CPB) in
      children undergoing surgical repair for congenital heart disease are extrapolated
      from adult data. Studies are needed that assess the optimal heparin dosing in
      these children, whose heparin clearance is increased compared with that in
      adults. METHODS: We assessed the effects of two commonly used doses of heparin in
      the prime solution at the start of CPB operation on plasma heparin levels, on
      thrombin production (thrombin-antithrombin III complexes, prothrombin fragment 1
      + 2, D-dimer, and antithrombin III), and on the risk of hemorrhage. Before CPB,
      48 children with congenital heart disease received heparin intravenously in a
      loading dose of 300 U/kg, followed by either 1 U/mL of heparin in the prime (low
      dose group: 22 patients-acyanotic, 9; cyanotic, 13) or 3 U/mL of heparin in the
      prime (group: high-dose, 26 patients-acyanotic, 15; cyanotic, 11). RESULTS: In
      all patients, CPB resulted in the generation of thrombin. The duration of CPB was
      a significant covariate factor for heparin levels (p = 0.002), thrombin
      production (p < 0.001), and postoperative blood loss (p < 0.001). In the patients
      in the high-dose group, the total heparin dose and the plasma heparin levels were
      higher (p = 0.0005 and 0.005, respectively) and the D-dimer levels tended to be
      lower (p = 0.06). The postoperative blood loss was higher in the cyanotic
      patients (p = 0.02; both high-dose and low-dose groups), with 2 cyanotic patients
      (1 in low-dose group, 1 in high-dose group) requiring reoperation, one of whom
      subsequently died. The increased heparin dose had no significant effect on the
      rate or volume of postoperative blood loss. CONCLUSIONS: Increasing the heparin
      dose in the prime solution from 1 to 3 U/mL increased the plasma heparin levels
      and showed a trend toward reducing the postoperative laboratory values indicative
      of fibrinolysis. Thrombin generation during CPB and the incidence of
      postoperative hemorrhage were not significantly altered. Larger randomized trials
      are needed to determine the optimal heparin-dosing regimen in patients with
      congenital heart disease.

PMID- 9033325
TI  - Outcomes after delayed sternal closure in pediatric heart operations: a 10-year
      experience.
AB  - BACKGROUND: Open heart operations in young children may lead to myocardial
      swelling and increased lung water. Decreased intrathoracic space may then make
      sternal closure difficult. Delayed sternal closure may be beneficial in this
      setting. Potential risks of delayed sternal closure are sepsis and sternal
      instability. METHODS: To assess these risks, we reviewed retrospectively 150
      consecutive children who underwent delayed sternal closure after repair of
      complex congenital cardiac defects. RESULTS: Diagnoses included transposition of
      the great arteries (66), total anomalous pulmonary venous drainage (11), and
      complete atrioventricular septal defects (10). Age at operation was 229 +/- 51
      days (mean +/- standard error of mean). Sixteen patients required extracorporeal
      membrane oxygenation. Survival was 88% (133 patients). The sternum was left open
      for 3.86 +/- 0.29 days. Fifteen patients had minor wound infections requiring
      antibiotics. No patient required reexploration for mediastinitis and no patient
      had an unstable sternum. CONCLUSIONS: Delayed sternal closure with sternal
      stenting and silicone membrane skin closure is a safe procedure in infants and
      children with compromised cardiac output after repair of congenital cardiac
      defects.

PMID- 9033326
TI  - Comparison of serum S-100 beta levels during CABG and intracardiac operations.
AB  - BACKGROUND: The risk of overt and subtle cerebral injury may be higher in
      intracardiac operation (ICO) rather than coronary artery bypass grafting (CABG).
      S-100 protein is a specific astroglial protein whose serum level increases after
      cerebral injury. Elevated serum levels of S-100 have been detected after adult
      cardiac operations and correlated with neurologic injury. METHODS: The level of S
      100 protein was measured serially over 24 hours in 40 patients (27 undergoing
      aortic valve replacement, 9 mitral valve replacement, 4 closure of atrial septal
      defect) undergoing ICO and 20 patients undergoing CABG. RESULTS: The groups were
      similar with respect to age and cardiopulmonary bypass times. The S-100 level was
      not elevated before operation in any patient. Peak S-100 levels were reached at
      skin closure, when 35 of the ICO patients (88%) and 13 of the CABG patients (65%)
      had elevated S-100 levels. At skin closure peak S-100 levels were significantly
      greater in the ICO group (median [interquartile range], 0.76 [0.44-1.16] versus
      0.3 [0-0.55] microgram/L; p < 0.01). At 5 hours S-100 levels were still elevated
      in 22 patients in the ICO group compared with 1 patient in the CABG group (p <
      0.01), and at 24 hours 17 ICO patients had persistently elevated S-100 levels in
      comparison with 2 in the CABG group (p < 0.01). One valve patient had a stroke 24
      hours after operation accompanied by a secondary increase in the S-100 level.
      There was no significant difference in postoperative S-100 levels between 5
      patients in the ICO group with a prior history of stroke and those without. The
      peak S-100 level correlated with patient age (r = 0.59; p < 0.001) but not with
      the duration of cardiopulmonary bypass or core temperature during the operation.
      CONCLUSIONS: Intracardiac operation results in a significantly greater elevation
      in S-100 levels than CABG. Elevated S-100 levels correlate with increasing
      patient age but not with the duration of cardiopulmonary bypass or intraoperative
      core temperature. These findings raise the possibility that ICO patients may be
      more vulnerable to even subtle levels of cerebral injury than CABG patients.

PMID- 9033327
TI  - Prospective, randomized, double-blind study of high-dose aprotinin in pediatric
      cardiac operations.
AB  - BACKGROUND: Perioperative aprotinin decreases postoperative blood loss in adults
      undergoing cardiac operations, but its role is less clear in children. Therefore,
      a trial of aprotinin in pediatric cardiac operations was conducted to study the
      efficacy of its use in children. METHODS: Forty-two patients were randomly
      assigned to receive either high-dose aprotinin or placebo. Aprotinin efficacy was
      assessed using time from protamine administration to skin closure, postoperative
      blood loss and hemoglobin loss, and postoperative transfusion requirements.
      Measures of fibrinolysis (fibrin degradation product titers) and platelet
      preservation (beta-thromboglobulin levels) were also assessed. RESULTS: There
      were no statistically significant differences between groups in any of the blood
      loss or transfusion parameters. Fibrin degradation product levels, measured 4
      hours postoperatively, had increased significantly for control patients, but
      remained unchanged for the aprotinin group (p < 0.02). beta-Thromboglobulin
      levels increased more rapidly during cardiopulmonary bypass in the control group
      (p = 0.03). CONCLUSIONS: Aprotinin appears to provide no clinical benefit in
      routine pediatric cardiac operations. A reduction in fibrinolysis, with perhaps
      an early preservation of platelet structure, is seen in the aprotinin group.

PMID- 9033328
TI  - Undertreatment and overtreatment of patients with infected antiarrhythmic
      implantable devices.
AB  - BACKGROUND: Infection of implantable defibrillators or pacemakers is a serious
      complication, reported with increasing frequency probably because of an increase
      in the total number of devices implanted due to a change in trends in the
      treatment of arrhythmias. This review is aimed to provide guidelines on how to
      deal with these infections and which method is most likely to be successful.
      METHODS: This is a review of 38 patients with infected antiarrhythmic implantable
      devices under three different plans of therapy. There were 17 implantable
      cardioverter defibrillators and 21 pacemakers. In 27, infection occurred after
      primary implantation (15 pacers, 12 implantable cardioverter defibrillators), and
      in 11 after replacement (six pacers, five implantable cardioverter
      defibrillators). Three therapeutic plans were identified. Group I (n = 12)
      received intravenous antibiotics without removal of the antiarrhythmic
      implantable device, but with relocation to a different area or plane, and with or
      without the use of a topical irrigating-suction system. Group II (n = 19) had
      complete removal of the system, 2 weeks of intravenous antibiotics, and
      implantation of a new unit followed by 10 more days of antibiotics. Group III (n
      = 7) underwent complete removal, 6 weeks of antibiotics, implantation of a new
      unit, and another 6 or more weeks of antibiotic therapy. RESULTS: Failure
      occurred in 100% of cases in group I. Groups II and III had complete clearing of
      infection and successful reimplantation of new systems with no recurring
      infections. Follow-up was 8 months to 5 years. Two deaths occurred, both in group
      I. Hospitalization for groups I and III was 104 days and 65 days, respectively,
      versus 22 days for group II. No deaths occurred in group II or III. CONCLUSIONS:
      With an infected antiarrhythmic implantable device, immediate removal of the
      entire unit is recommended, followed by 2 weeks of intravenous antibiotics,
      implantation of a new system, and 10 more days of postoperative antibiotics. This
      regimen is sufficient to cure the problem. No attempts should be made to save an
      infected system from removal because it endangers the patient's life, prolongs
      hospitalization, increases costs, and most likely will fail.

PMID- 9033330
TI  - Predictors of stroke risk in coronary artery bypass patients.
AB  - BACKGROUND: Stroke occurs after coronary artery bypass grafting with an incidence
      ranging between 0.8% and 5.2%. To identify factors associated with stroke, we
      prospectively examined a study cohort and tested findings in an independent
      validation sample. METHODS: The study cohort comprised 456 patients undergoing
      coronary artery bypass grafting only, and the validation sample comprised 1,298
      patients. Stroke was detected postoperatively by the study team and confirmed by
      neurologic consultation and computed tomographic scanning. RESULTS: Five factors
      taken together were correlated with stroke: previous stroke, presence of carotid
      bruit, history of hypertension, increasing age, and history of diabetes mellitus.
      The only significant intraoperative factor was cardiopulmonary bypass time.
      Probabilities were calculated, and patients were placed into low, medium, and
      high stroke-risk groups. In the validation sample, this model was able to rank
      the majority of patients with stroke into the high-risk group. CONCLUSIONS: These
      five factors taken together can identify the risk of stroke in patients having
      coronary artery bypass grafting. Recognition of the high-risk group will aid
      studies on the mechanism and prevention of stroke by modification of surgical
      procedures or pharmacologic intervention.

PMID- 9033329
TI  - Cognitive outcome after coronary artery bypass: a one-year prospective study.
AB  - BACKGROUND: Cognitive deficits have been reported in patients after coronary
      artery bypass grafting, but the incidence of these deficits varies widely. We
      studied prospectively the incidence of cognitive change and whether the changes
      persisted over time. METHODS: Cognitive testing was done preoperatively and 1
      month and 1 year postoperatively in 127 patients undergoing coronary artery
      bypass grafting. Tests were grouped into eight cognitive domains. A change of 0.5
      standard deviation or more at 1 month and 1 year from patient's preoperative Z
      score was the outcome measure. RESULTS: We identified four main outcomes for each
      cognitive domain: no decline; decline and improvement; persistent decline; and
      late decline. Only 12% of patients showed no decline across all domains tested;
      82% to 90% of patients had no decline in visual memory, psychomotor speed, motor
      speed, and executive function; 21% and 26% had decline and improvement in verbal
      memory and language; approximately 10% had persistent decline in the domains of
      verbal memory, visual memory, attention, and visuoconstruction; and 24% had late
      decline (between 1 month and 1 year) in visuoconstruction. CONCLUSIONS: This
      study establishes that the incidence of cognitive decline varies according to the
      cognitive domain studied and that some patients have persistent and late
      cognitive changes in specific domains after coronary artery bypass grafting.

PMID- 9033331
TI  - Clinical application of transluminal endovascular graft placement for aortic
      aneurysms.
AB  - BACKGROUND: In recent years, transluminal endovascular graft placement techniques
      have been developed for the treatment of aortic aneurysms. We report our initial
      clinical experience with endovascular graft placement using a graft developed in
      our laboratory. METHODS: The procedure was performed in 20 patients with a
      diagnosed aortic aneurysm. The graft is constructed from a Dacron cylinder, and
      the surface of the graft is supported with multiple rings of extraflexible wire.
      After the compactly folded graft is delivered through the sheath to the
      predetermined target point, the graft is deployed and then pressed against the
      vessel by balloon inflation. Straight graft insertion was attempted in 10
      patients, bifurcated graft insertion in 8, and branched graft insertion in 2.
      RESULTS: Graft placement was successful in 19 of the patients and unsuccessful in
      1. There were no cases of graft migration, aneurysm rupture, or graft destruction
      during a mean follow-up period of 9 months. CONCLUSIONS: Initial clinical results
      demonstrated the efficacy and safety of endovascular graft placement using this
      graft.

PMID- 9033332
TI  - Double mycotic aneurysms of the ascending aorta.
AB  - Infection in the vascular tree has been proved to be one of the greatest
      challenges for cardiovascular surgeons. Of these, mycotic aneurysms of the
      ascending aorta were considered to be almost always lethal until recently. A
      thorough survey of the literature indicates that only 42 cases of mycotic
      aneurysm of the ascending aorta have been reported. All the reported cases of
      mycotic aneurysm of the ascending aorta were a single lesion in the ascending
      aorta except a case reported in 1993. This report describes an additional case of
      double mycotic aneurysms of the ascending aorta caused by Pseudomonas infection.

PMID- 9033333
TI  - Esophageal leiomyomatosis involving trachea: surgical resection and repair.
AB  - We report the case of a 26-year-old man with diffuse esophageal leiomyomatosis
      involving the trachea. The tumor was resected by total esophagectomy and partial
      resection of the trachea and the left main bronchus. The tracheobronchial defect
      was repaired with a free forearm skin graft with satisfactory outcome. This
      approach offers good long-term prospects.

PMID- 9033334
TI  - ECMO and inhaled nitric oxide for cardiopulmonary failure after heart
      retransplantation.
AB  - Cardiopulmonary failure occurred in a 62-year-old patient a few hours after
      emergency cardiac retransplantation. Venoarterial extracorporeal membrane
      oxygenation was required to support biventricular dysfunction; thereafter,
      inhaled nitric oxide was given for residual hypoxemia and pulmonary hypertension.
      We report survival after venoarterial extracorporeal membrane oxygenation and
      inhaled nitric oxide treatment for both heart and lung failure in a heart
      recipient.

PMID- 9033335
TI  - Operation for type B aortic dissection using hypothermic selective cerebral
      perfusion.
AB  - A 56-year-old man who had a huge type B dissecting aortic aneurysm extending from
      the distal arch to the thoracoabdominal aorta underwent replacement of the
      descending thoracic and thoracoabdominal aorta under hypothermic circulatory
      arrest with selective cerebral perfusion. The intercostal arteries at the T-8 to
      T-11 level were preserved with beveled distal anastomosis, and the celiac artery
      and the intercostal arteries at the T-5 and T-6 levels were reconstructed. The
      patient recovered uneventfully and is presently doing well 1 year after the
      operation.

PMID- 9033336
TI  - Hemangiopericytoma of the chest wall.
AB  - We treated a 79-year-old woman with hemangiopericytoma of the chest wall. This is
      a very rare entity, with only a total of 12 cases including our case reported in
      Japan. There is a predominance of women (10 female patients and two male
      patients) and a predilection for the right side (9 in the right side and 3 in the
      left side).

PMID- 9033337
TI  - Rare complication of retrograde cardioplegia: inner wall perforation of the right
      atrium.
AB  - Retrograde cardioplegia has been widely applied with satisfactory results. This
      report presents a case in which the retrograde cannula was inserted into the
      coronary sinus by penetrating the inner wall of the right atrium rather than
      through the orifice of the coronary sinus. Surgeons should be cautious of this
      possibility, particularly in patients with a dilated right atrium in which the
      space between trabeculae is enlarged and the atrial tissue is friable. Under this
      situation, the tip of the cannula is easily caught in such a space and may
      penetrate the wall of the right atrium, which affects the delivery of
      cardioplegia.

PMID- 9033338
TI  - Prosthetic mitral valve replacement: late complications after native valve
      preservation.
AB  - Preservation of the mitral valve leaflet and tensor apparatus during valve
      replacement is believed to maintain left ventricular performance. The routine use
      of this technique may lead to left ventricular outflow or inflow obstruction as
      illustrated in the present report. We recommend mobilization or excision of the
      anterior mitral valve leaflet and preservation of the posterior leaflet if
      replacement of the valve is contemplated for incompetence.

PMID- 9033339
TI  - Calcifying fibrous pseudotumor of the mediastinum.
AB  - Calcifying fibrous pseudotumor has recently been described in the soft tissues.
      It is a rare benign lesion characterized by the presence of abundant hyalinized
      collagen with psammomatous or dystrophic calcifications and lymphoplasmacytic
      infiltrate. We report a case of a young woman with a mediastinal mass treated by
      a complete resection. The mass had all the pathologic features of calcifying
      fibrous pseudotumor.

PMID- 9033340
TI  - Surgical treatment of dissecting aneurysm of the interventricular septum.
AB  - Two extremely rare cases of dissecting aneurysm of the interventricular septum
      associated with aortic incompetence are reported. One was complicated with an
      aneurysm of the left coronary sinus of Valsalva, and the other may have been the
      result of trauma. Surgical operation involved resection or repair of the aneurysm
      and replacement of the aortic valve. Both patients recovered uneventfully. Early
      diagnosis and surgical intervention are emphasized.

PMID- 9033341
TI  - Separate-hypothermia retrograde cerebral perfusion.
AB  - We have developed a technique of cerebral protection in which the blood for the
      retrograde cerebral perfusion from the superior vena cava cannula is cooled down
      to 10 degrees C, while the core temperature is maintained at moderate
      hypothermia. We performed graft replacement of the ascending and aortic arch in 2
      patients with dissecting aneurysm using this method. This technique may provide
      excellent cerebral protection without coagulation disorder.

PMID- 9033342
TI  - Commissurotomy and bileaflet pericardial augmentation-resuspension for bicuspid
      aortic valve stenosis.
AB  - We describe a valve reconstruction technique for congenital bicuspid aortic valve
      stenosis employing a commissurotomy, resection of raphe between conjoint
      leaflets, and bileaflet augmentation-resuspension using a triangular strip of
      glutaraldehyde-preserved autologous pericardium. This maneuver relieves aortic
      valve stenosis, preserves the native valve leaflets, reproduces the natural
      trileaflet scalloping of the aortic valve annulus, and improves cusp coaptation.

PMID- 9033343
TI  - Left atrial myxoma in a preschool child.
AB  - A case of left atrial myxoma successfully removed using cardiopulmonary bypass in
      a 5-year-old child is presented. Review of the literature emphasizes the rarity
      and clinically aggressive behavior of this tumor in this age group.

PMID- 9033344
TI  - Postpneumonectomy stump fistula in a ventilated patient.
AB  - The development of a postpneumonectomy stump fistula in a ventilated patient is a
      feared and frequently fatal event. Furthermore, the necessity of a pneumonectomy
      from sequelae of blunt trauma is rare. We describe the salvage of a young patient
      with a combination of the above events. The method involves the use of a simple
      intravenous bag "plombage" in combination with a regional thoracoplasty to
      buttress a resutured bronchial stump.

PMID- 9033345
TI  - Transhiatal herniation of colon after esophagectomy and gastric pull-up.
AB  - Transhiatal herniation of colon is uncommon after transhiatal esophagectomy. Two
      patients with this complication are presented. Presenting symptoms vary depending
      on the size and contents of the hernia. Patients may be asymptomatic. The
      diagnosis is suggested by plain chest radiography, and treatment, in symptomatic
      patients, is surgical reduction of the hernia via a laparotomy.

PMID- 9033347
TI  - Technique for reconstruction of the sinotubular junction.
AB  - Correct geometric relationships between the annulus and sinotubular junction
      during stentless valve implantation are critical to minimize the development of
      insufficiency. Some patients with aortic valve disease have dilatation of the
      sinotubular junction and are unable to have a stentless valve placed by standard
      techniques. We recently encountered such a patient and reconstructed the
      sinotubular junction by aortic crenation. Multiple interrupted plicating sutures
      were used to reduce the aorta from a diameter of 42 mm to 28 mm. This method
      allows tailoring of the aorta to appropriate size by varying the number of
      crenating sutures.

PMID- 9033348
TI  - "LIMA fissure" for a tension-free IMA graft in emphysema.
AB  - Tension on the mammary artery pedicle is a major concern during coronary artery
      bypass in asthmatic patients with emphysematous lungs. We are sharing here a
      simple and effective solution to this problem.

PMID- 9033346
TI  - Complex thoracic vascular injury repair using deep hypothermia and circulatory
      arrest.
AB  - A 61-year-old man with a penetrating injury to the innominate artery, left common
      carotid artery, and left subclavian artery at their origins from the aortic arch
      with associated injuries to both innominate veins and an innominate artery to
      vein fistula after a single stab wound is described. The patient was managed
      successfully using cardiopulmonary bypass together with deep hypothermia and
      circulatory arrest. Presentation and management are discussed.

PMID- 9033349
TI  - Transmanubrial osteomuscular sparing approach for apical chest tumors.
AB  - The transclavicular approach improved the treatment of apical chest tumors.
      However, removing the internal half of the clavicle and sectioning its muscular
      insertions led to serious postoperative alterations. We propose a transmanubrial
      approach, through a manubrial L-shaped transection and first costal cartilage
      resection, which allows retraction of an osteomuscular flap including but sparing
      the clavicle and all its muscular insertions. The elevation of the osteomuscular
      flap affords excellent access to the subclavicular region with safe control and
      resection of neurovascular outlet structures during the resection of apical chest
      tumors. Shoulder articulations and stability of the scapular girdle are
      respected, thus avoiding functional and cosmetic consequences of clavicle
      resection.

PMID- 9033350
TI  - Improved method for direct coronary grafting without CPB via anterolateral small
      thoracotomy.
AB  - We describe an improved method of minimally invasive coronary artery bypass
      grafting that facilitates the anastomosis on the beating heart by means of a
      rigid and simple coronary stabilizer. This technique permits anastomosis of the
      left internal mammary artery to the left anterior descending coronary artery
      through a small (8 to 10 cm) left anterolateral thoracotomy without
      cardiopulmonary bypass. We successfully used this technique in 20 primary
      coronary artery bypass grafting operations, without in-hospital mortality or any
      other cardiac complication.

PMID- 9033351
TI  - "Patch-glue" annular reconstruction for mitral valve replacement in severely
      calcified mitral annulus.
AB  - Mitral valve replacement in severe annular calcification may be complicated by
      atrioventricular rupture, left circumflex coronary artery injury, and
      thromboembolic events. Mitral valve replacement was performed in 2 patients with
      massive annular calcification, by suturing a Tissucol fibrin glue-treated Teflon
      patch on the posterolateral atrial wall. After 30 and 34 months, respectively,
      the valve was normally functioning and the patients were asymptomatic and free
      from hemorrhagic and thromboembolic events.

PMID- 9033352
TI  - Spool-like stent for the open sternum after cardiac operations.
AB  - Severe edematous heart after a cardiac operation is impossible to treat if there
      is compression of the heart due to the sternum. In these patients delayed sternal
      closure may be a useful procedure until the heart decreases in size. We devised a
      spool-like stent for the open sternum to maintain the optimal cardiac space for
      the severely edematous heart and to fix the chest wall to allow for management
      while the sternum is open.

PMID- 9033353
TI  - Thoracic surgery techniques of Serefeddin Sabuncuoglu in the fifteenth century.
AB  - Serefeddin Sabuncuoglu (1385 to 1470?) is known to be the author of the first
      surgery textbook, namely Cerrahiyyet'ul Haniyye (Imperial Surgery), written in
      Turkish in 1465. It is the first book to contain colored illustrations of
      surgical procedures, incisions, and instruments in the Turkish-Islamic medical
      literature. He was the first man to illustrate and mention introduction of a tube
      into the pharynx and upper esophagus, removal of foreign bodies in the esophagus
      by special instruments of his own design, and use of a silver ringlet in a man
      after tracheotomy. He also described and illustrated reduction of sternal
      fractures, thoracic puncture through the intercostal space for drainage of
      empyema cavities, and treatment of rib fractures that have severed the diaphragm.
      He was a humble, curious, and intelligent surgeon, and also a calligrapher and a
      miniature artist.

PMID- 9033354
TI  - Antimyosin antibodies in cardiac rejection.
AB  - The antimyosin antibody is often applied to find out scintigraphically whether
      myocarditis, myocardial infarction, or (recently) cardiac rejection is present.
      In the past, a lot of experimental work and clinical studies were done to
      determine its position, especially for the noninvasive detection of cardiac
      transplant rejection. Efforts are focused on comparing its diagnostic benefit
      with that of endomyocardial biopsy. The feasibility of rejection grading and
      diagnostic reliability are essential parts of this discussion. On the basis of
      large prospective clinical studies and the information from several experimental
      animal trials, some important findings can be assumed. Antimyosin scintigraphy
      after the application of indium 111-labeled antimyosin antibodies is a reliable
      tool to detect or exclude noninvasively cardiac rejection in adults and children.
      A distinction among three rejection intensities is possible, as confirmed by
      immunohistologic examinations. Antimyosin scintigraphy is an important
      noninvasive method for detecting cardiac rejection, with considerable advantages
      compared with endomyocardial biopsy.

PMID- 9033355
TI  - Endothelial cell injury in cardiovascular surgery: the intimal hyperplastic
      response.
AB  - Arteries and veins respond to injury by a healing process that includes the
      development of a neointima. This response to injury is implicated as the primary
      cause of failure after arterial reconstruction. Because it is an integrator and
      transmitter of blood flow variations, inflammation, and growth stimuli, the
      endothelium is a potent regulator of long-term arterial wall mass changes. The
      contribution of the endothelium to intimal development depends on the type of
      arterial conduit. In arteries, the growth of the intima stops when the
      endothelium has regrown. In synthetic grafts, the endothelium stabilizes intimal
      growth. Hence, the mere presence of endothelial cells can influence intimal
      changes in arterial conduits. Understanding endothelial biology should help us
      define methods to prevent cell proliferation, extracellular matrix accumulation,
      intimal hyperplasia, and vessel narrowing.

PMID- 9033356
TI  - As originally published in 1989: Intraoperative evaluation of atrioventricular
      septal defect repair by color flow mapping echocardiography. Updated in 1997.

PMID- 9033357
TI  - As originally published in 1989: The effect of fluorocarbon emulsion on 24-hour
      canine heart preservation. Updated in 1997.

PMID- 9033358
TI  - Periprosthetic mitral leakage in a patient with a prior aortic valve prosthesis.

PMID- 9033359
TI  - Pseudovascular tubes obscure transmyocardial revascularization.

PMID- 9033360
TI  - Microvascular reactivity after cardioplegia.

PMID- 9033361
TI  - Aortic valve replacement with a pericardial bioprosthesis.

PMID- 9033362
TI  - Prosthetic mitral valve thrombosis after replacement with preservation of all
      chordae.

PMID- 9033363
TI  - Surgical management of primary pulmonary artery sarcoma.

PMID- 9033365
TI  - Urokinase-coated flat drain for pediatric cardiac operations.

PMID- 9033364
TI  - Spiral staircase esophageal peristalsis.

PMID- 9033366
TI  - Urological society.

PMID- 9033367
TI  - Newer approaches to regional cancer therapy through tumour immunology: is there a
      'breakthrough'?
AB  - Eagerly awaited 'breakthroughs' in immunological treatment have in the past been
      disappointingly unsuccessful in changing the outlook for most patients with
      otherwise incurable cancers. Many hopeful agents have been studied in therapeutic
      trials but each in turn has proven to be largely disappointing. One of the latest
      products of immunological research, tumour necrosis factor (TNF) was found to be
      too toxic for systemic use but has been found to be highly effective in improving
      the results of treatment of melanoma when used in a closed-circuit perfusion
      system in combination with another chemotherapeutic agent. In the past the use of
      closed-circuit perfusion has been confined to limbs, but techniques have recently
      been developed to apply closed-circuit perfusion to liver, pelvic organs, and
      some abdominal regions including pancreas. The potential for studies of TNF in
      combination with chemotherapy in closed-circuit perfusion treatment of otherwise
      resistant cancers in these organs and tissue regions has been greatly expanded.
      In many cancer treatment centres in the past there has been a reluctance to use
      and to acknowledge the benefits of regional delivery of anti-cancer chemotherapy.
      The need for these techniques in the safe and effective use of TNF has further
      confirmed the importance of these methods in comprehensive cancer treatment
      centres, and the need for further studies and better understanding of the use of
      regional and closed-circuit perfusion methods.

PMID- 9033369
TI  - Surgical treatment of breast cancer in New South Wales 1991, 1992.
AB  - BACKGROUND: The purpose of this study was to examine existing data on women
      diagnosed with breast cancer in New South Wales in 1991 and 1992 and to describe
      surgical treatments received on an inpatient basis. METHODS: Analyses were based
      on the linkage of two databases: the New South Wales Central Cancer Registry and
      the New South Wales Health Department's Inpatient Statistics Collection. Data
      were limited to women who were resident and treated in New South Wales. Main
      analyses were restricted to definitive surgical procedures. RESULTS: Thirty-six
      per cent of women treated surgically for breast cancer in 1991 had breast
      conserving therapy. This had increased to 39% in 1992. There were substantial
      geographical variations in the use of breast-conserving therapy in New South
      Wales which could not be explained by patient characteristics. Age, degree of
      spread at diagnosis, and area health service/ health region were all found to
      have an independent association with the probability of having a mastectomy.
      CONCLUSIONS: Women with a localized degree of spread living in non-metropolitan
      areas (Health Regions) were almost twice as likely to have a mastectomy as
      compared with similar women who were resident in metropolitan areas (Area Health
      Services). The concentration of radiotherapy services may have contributed to the
      urban/rural variation in breast-conserving therapy in New South Wales, but it is
      also likely that some of the variations that were observed may be a reflection of
      the failure of clinicians to use best current practice.

PMID- 9033368
TI  - Intra-operative implant brachytherapy in the management of soft-tissue sarcomas.
AB  - BACKGROUND: The management of localized soft-tissue sarcomas remains complex.
      This is a retrospective review of a single institution experience with manual
      afterloaded brachytherapy following intra-operative implantation of the tumour
      bed during surgery. METHODS: Twelve patients over a 3-year period had resection
      for localized soft-tissue sarcomas and desmoids with insertion of intra-operative
      brachytherapy implants combined with resection for localized soft-tissue
      sarcomas. Manual afterloading of the implant with iridium wires was performed
      postoperatively in all patients. The low dose rate brachytherapy dose varied from
      13 to 20 Gy. Supplementary external beam radiation was administered pre
      operatively or postoperatively to bring the total dose of adjuvant irradiation to
      60-65 Gy. RESULTS: After a median follow-up period of 29 months, the 3-year local
      disease-free survival rate was 63%. The 3-year actuarial survival rate was 83%.
      There were no failures within the high-dose region of the implant, although two
      patients had locoregional failures adjacent to the tumour bed at the edge of the
      radiation field. Three patients developed distant metastases. Side effects were
      noted in five patients. Wound breakdown and delayed wound healing occurred in two
      patients. One patient required an amputation as a result of chronic non-healing
      and wound pain. Pathological fractures occurred in two patients. Those patients
      who did not develop wound breakdown had good cosmetic and functional outcomes.
      CONCLUSION: Intra-operative implantation of the tumour bed in combination with
      tumour resection for soft-tissue sarcomas results in a high degree of local
      control with acceptable complications. This modality offers the patient a high
      chance of avoiding a more radical surgical procedure such as limb amputation.

PMID- 9033370
TI  - Management of seminoma of the testis: recommendations based on treatment results.
AB  - BACKGROUND: The results of management of seminoma of the testis at the Department
      of Radiation Oncology St Vincent's Hospital, Sydney were evaluated
      retrospectively to: (i) establish that outcomes were in keeping with published
      results from centres in Australia and overseas; (ii) assess the impact of
      chemotherapy on management; and (iii) to determine 'best practice' management
      protocols based on our results and a review of the relevant literature. METHODS:
      (i) Assessment of treatment results for stage I and II seminoma of the testis
      treated by post-orchidectomy radiotherapy and/or chemotherapy at St Vincent's
      Hospital between 1979 and 1993; (ii) literature review of published data from
      Australian and overseas centres on the management of seminoma of the testis, and
      in particular the use of surveillance or chemotherapy either alone, at time of
      relapse or combined with radiotherapy; and (iii) development of recommendations
      for use as management protocols in our department. RESULTS: Our data and a review
      of the literature suggest that post-orchidectomy radiotherapy with chemotherapy
      for relapse in stage I and IIA disease results in long-term cure rates
      approaching 100%. Treatment with chemotherapy either routinely or selectively or
      using a surveillance policy is unlikely to show any improvement in outcome and
      may be less cost-effective and/or produce increased morbidity and the risk of
      secondary leukaemia. For stage IIB disease (5-10 cm) the use of initial
      combination chemotherapy with or without subsequent radiotherapy did not appear
      to give better outcomes than initial radical radiotherapy alone, reserving
      chemotherapy or further radiotherapy for relapse. For bulkier stage IIB disease
      (> 10 cm), the use of initial chemotherapy plus consolidation radiotherapy
      appeared to be an appropriate treatment. CONCLUSIONS: Management protocols for
      seminoma of the testis at St Vincent's Hospital, Sydney Department of Radiation
      Oncology currently are (i) stage I, IIA and IIB (5-10 cm): post-orchidectomy
      radiotherapy alone with chemotherapy or further radiotherapy for relapse; and
      (ii) stage IIB (> 10 cm) disease: initial chemotherapy post-orchidectomy followed
      by radiotherapy to sites of initial disease involvement.

PMID- 9033371
TI  - 'Trash foot' following operations involving the abdominal aorta.
AB  - BACKGROUND: Acute lower limb ischaemia following aortic surgery is commonly
      termed 'trash foot'. The exact cause of the ischaemia is unknown, but it has been
      attributed to athero-emboli from native arteries, thrombo-emboli from any
      prosthetic graft or thrombosis of small vessels in the distal arterial tree.
      METHODS: Review of 1601 aortic reconstructions performed between 1976 and 1995.
      RESULTS: 'Trash foot' occurred in 32 patients (44 limbs): 23 cases followed
      aortic aneurysm repair and nine cases followed an aorto-femoral bypass for
      occlusive disease. Six cases of 'trash foot' (13.6%) underwent an early
      amputation (one above-knee, two below-knee and three cases of amputation of one
      or more toes) while a further nine cases (20.5%) underwent a delayed amputation
      (four above the knee, two below the knee and three cases of toe amputation).
      Eight patients (25%) with 'trash foot' died within 30 days of surgery.
      CONCLUSION: 'Trash foot' following aortic surgery is an unwelcome complication
      that is associated with a high morbidity and mortality. Attempts to reduce the
      incidence involve early mobilization and clamping of the iliac arteries, and
      irrigation of the aortic anastomosis and graft with heparin saline solution.

PMID- 9033372
TI  - Arterial injury in the lower limb from blunt trauma.
AB  - BACKGROUND: The present study was performed to identify the factors associated
      with amputation in patients with blunt injuries to the lower limb associated with
      arterial injury. The ability of a scoring system to predict the outcome was
      tested. METHODS: There were 122 lower limb arterial injuries in 119 patients
      treated at the Royal Adelaide Hospital in the years 1962-1994. Prognostic factors
      considered were the site of the injury, the severity of the soft-tissue injury
      and shock, the presence of associated injuries and a description of the bone or
      joint injury. The mangled extremity severity score (MESS) was calculated
      retrospectively for each patient. RESULTS: The outcome was primary amputation in
      27 patients, delayed amputation in 36 patients and limb salvage in 59 patients.
      The seven deaths were all due to associated injuries. Factors associated with
      amputation were the severity of shock and soft-tissue injury (P < 0.01), and
      tibial artery injury compared with more proximal injury (P < 0.001). Factors that
      did not affect outcome included delay before repair, method of fracture fixation,
      or performance of fasciotomy. Amputation was performed in 48/71 (68%) patients
      with Gustilo type-IIIC fractures of the tibia. Applying the MESS to our patients
      resulted in a positive predictive value (PPV) of 71%, a negative predictive value
      (NPV) of 84% and an overall accuracy of prediction of 75%. CONCLUSIONS: The major
      factor determining outcome was the severity of the soft-tissue injury.
      Progressive necrosis and infection was a major cause of late amputation. The MESS
      is not sufficiently precise to allow the decision regarding amputation to be made
      at the initial operation.

PMID- 9033373
TI  - 37 kBq 14C-urea breath test and gastric biopsy analyses of H. pylori infection.
AB  - BACKGROUND: The treatment of H. pylori-associated gastroduodenal disease is
      increasingly aimed at bacterial eradication which requires follow-up assessment
      of therapeutic effectiveness and re-infection. A simplified 37 kBq 14C-urea
      breath test for H. pylori infection has been developed. METHODS: The 37 kBq 14C
      urea breath test was compared with biopsy urease (CLO) and histological analyses
      of gastric-biopsies obtained from 63 patients undergoing endoscopy. RESULTS: The
      30-min breath test correlated closely with biopsy findings, had a sensitivity of
      100%, a specificity of 95% and a positive predictive value of 92%. CONCLUSIONS:
      The simplified, low-dose, 14C-urea breath test is a convenient, low-cost,
      transportable means of facilitating the management of H. pylori-associated
      diseases.

PMID- 9033374
TI  - Experimental skeletal muscle grafts as a model of regeneration.
AB  - BACKGROUND: It is now well established that mature skeletal muscle has the
      ability to regenerate, and reports on this phenomenon have existed in the
      research literature for some 40 years. However, it is only relatively recently,
      largely due to the advances in microsurgery, that practising surgeons can make
      direct use of the regenerative ability of skeletal muscle. METHODS: Most of the
      key data on skeletal muscle regeneration have come from experimental studies on
      muscle grafts in small animal models. One such model is the transplantation of
      the extensor digitorum muscle of the mouse or rat into the contralateral site, or
      the relocation of this muscle onto the surface of the tibialis anterior muscle.
      These and other models, together with the important cellular mechanisms involved
      in the regeneration of skeletal muscle, are reviewed briefly in this article.
      RESULTS: Skeletal muscle cells regenerate rapidly in muscle grafts, arising from
      satellite cells in the surviving peripheral fibres of the graft within 2 days
      after grafting. The resultant myoblasts progress towards the necrotic graft
      centre and occupy the area by 5 days. Revascularization commences at 3 days after
      grafting, but reinnervation takes many weeks to complete. CONCLUSIONS: With the
      established knowledge on skeletal muscle regeneration, largely gained from
      experimental studies of muscle grafts; an understanding of these mechanisms
      should now be fundamental knowledge for today's practising surgeons.

PMID- 9033375
TI  - The 'urogenital diaphragm', external urethral sphincter and radical
      prostatectomy.
AB  - BACKGROUND: The present study was performed to determine whether a 'urogenital
      diaphram' exists, to examine the true nature of the striated external urethral
      sphincter and to evaluate whether the standard technique for radical
      prostatectomy damages the external sphincter. METHODS: Fifty radical
      prostatectomies were performed using optical magnification and the dorsal
      bunching technique, and the external sphincter was carefully examined. Ten human
      cadavers and one 5-year-old baboon were dissected with longitudinal (sagittal)
      and transverse sections being taken through the prostate apex, membranous and
      bulbar urethrae. During the standard technique for dorsal vein control during
      radical prostatectomy, the tissue incorporated within the ligature was examined
      for striated muscle. RESULTS: No 'urogenital diaphragm' could be demonstrated in
      any human or baboon tissue. The striated external urethral sphincter is a
      cylinder of muscle surrounding the membranous urethra, extending from the
      perineal membrane to the prostate and continuing over the prostate as part of the
      anterior fibromuscular stroma. Striated muscle was present in the ligated
      material from the dorsal venous complex. CONCLUSIONS: The 'urogenital diaphragm'
      is a myth. The standard technique of radical prostatectomy significantly damages
      the external sphincter.

PMID- 9033376
TI  - A critical evaluation of free paper abstracts accepted for the 1996 RACS Annual
      Scientific Congress.
AB  - BACKGROUND: Abstracts form a major part of medical information dissemination and
      a measure by which papers are accepted for meetings. Concerns have been raised
      about the quality of abstracts presented to the Annual Scientific Congress (ASC)
      and second, about the validity of the term 'scientific' to describe this meeting.
      METHODS: A critical evaluation was made of all free paper abstracts in general
      surgery from the ASC 1996, using a standard assessment process. They were judged
      on presentation and content. A direct comparison was made to the content of
      abstracts from the Surgical Research Society of Australasia 1995(SRSA) meeting.
      RESULTS: The ASC abstracts scored 87% (6.1/7.0) for presentation but with clear
      deficiencies. The score of 49% (7.4/15.0) for the content of the ASC abstracts
      was significantly less than the score of 65% (9.8/15.0) that was attained by the
      SRSA abstracts when assessed on content. (Wilcoxon rank sum test, P < 0.000002.)
      CONCLUSIONS: The quality of the presentation of abstracts was adequate but could
      clearly be improved, especially with regard to the specific instructions to
      authors. The ASC abstracts were significantly less scientific in content that
      those of the SRSA abstracts. The criteria used to select abstracts for the ASC
      should be reviewed and the title of the annual College meeting should be
      reconsidered.

PMID- 9033378
TI  - Immediate breast reconstruction in Chinese women using the transverse rectus
      abdominis myocutaneous (TRAM) flap.

PMID- 9033379
TI  - Fatigue fracture of the medial malleolus in a junior rollerskater.

PMID- 9033380
TI  - Trainee selection.

PMID- 9033377
TI  - Breast cancer: current issues in diagnosis and treatment.
AB  - The diagnosis and treatment of breast cancer in Australia has changed in response
      to new technologies and cultural influences which have emphasized the importance
      of psychological and social aspects of breast cancer. In this review article,
      recent developments are examined in relation to current surgical practice.
      Changes in the incidence of breast cancer, the effect of mammographic screening
      on the outcome of treatment, the increasing use of breast-conserving surgery, the
      timing of surgery in relation to the menstrual cycle and the importance of risk
      factors for breast cancer are all considered. Breast cancer is a potentially
      curable disease. Early detection and conservative surgery provide a framework for
      disease control.

PMID- 9033382
TI  - Adenocarcinoma complicating an anorectal sinus in a patient with Crohn's disease.

PMID- 9033381
TI  - Mullerian duct cyst associated with a posteriorly prolapsing verumontanum.

PMID- 9033383
TI  - Recurrent leiomyosarcoma of the inferior vena cava.

PMID- 9033384
TI  - Spontaneous bladder perforation: an unusual management problem of tuberculous
      cystitis.

PMID- 9033385
TI  - Breast metastases from primary leiomyosarcoma.
AB  - Two cases of metastatic leiomyosarcoma of the breast are presented. The reasons
      why they are considered as secondary tumours and not primary tumours are also
      discussed.

PMID- 9033386
TI  - Structure of a selectin-like mutant of mannose-binding protein complexed with
      sialylated and sulfated Lewis(x) oligosaccharides.
AB  - Rat serum mannose-binding protein in which residues 211-213 have been changed to
      the Lys-Lys-Lys sequence found in E-selectin binds HL-60 cells and the
      oligosaccharide 3'-NeuAc-Le(x). To understand how this mutant, designated K3,
      mimics the carbohydrate-binding properties of E-selectin, structures of K3 alone
      and in complexes with 3'-NeuAc-Le(x), 3'-sulfo-Le(x) and 4'-sulfo-Le(x) have been
      determined at 1.95-2.1 A resolution by X-ray crystallography. The region of K3
      that interacts with bound oligosaccharides superimposes closely with the
      corresponding region of unliganded E-selectin. In each of the oligosaccharide
      protein complexes, the 2- and 3-OH of Fuc coordinate Ca2+ and form a network of
      cooperative hydrogen bonds with amino acid side chains that also coordinate the
      Ca2+. Lys211 of the K3 mutant, which corresponds to Lys111 of E-selectin,
      interacts with each of the three bound ligands: the N zeta atom donates a
      hydrogen bond to the 4-OH of Gal in 3'-NeuAc-Le(x), forms a water-mediated
      hydrogen bond with the 4-OH of Gal in 3'-sulfo-Le(x), and forms a salt bridge
      with the sulfate group of 4'-sulfo-Le(x). Lys213 packs against an otherwise
      exposed aromatic residue and forms a water-mediated hydrogen bond with Lys211
      which may help to position that residue for interactions with bound
      oligosaccharides. These structures are consistent with previous mutagenesis and
      chemical modification studies which demonstrate the importance of the Ca2+
      ligands as well as Lys111 and Lys113 for carbohydrate binding in the selectins,
      and they provide a structural basis for understanding the selective recognition
      of negatively charged Le(x) derivatives by the selectins.

PMID- 9033387
TI  - Bromocontryphan: post-translational bromination of tryptophan.
AB  - We demonstrate that post-translational bromination of a tryptophan residue occurs
      in the biologically active octapeptide bromocontryphan, purified and
      characterized from Conus radiatus venom. Clones encoding bromocontryphan were
      identified from a cDNA library made from C. radiatus venom ducts. The mRNA
      sequence obtained predicts a prepropeptide which has the mature peptide sequence
      at the C-terminal end, with the L-6-bromotryptophan residue encoded by UGG, the
      Trp codon. These data provide the first direct evidence for post-translational
      bromination of a polypeptide which is translated through the normal cellular
      machinery. In addition to bromination, the peptide, which induces a "stiff tail"
      syndrome in mice, has several other modifications as shown by the sequence
      [Formula: See Text] in which Hyp = hydroxyproline. Asterisks indicate post
      translational modifications (left to right): proteolytic cleavage at the N
      terminus; hydroxylation of Pro3; epimerization of Trp4; bromination of Trp7, and
      C-terminal amidation. Bromocontryphan appears to have the highest density of post
      translational modifications known among gene-encoded polypeptides. The overall
      result is a molecule which closely resembles marine natural products produced
      through specialized biosynthetic pathways comprising many enzyme-catalyzed steps.

PMID- 9033388
TI  - Crosslinking kinetics of the human transglutaminase, factor XIII[A2], acting on
      fibrin gels and gamma-chain peptides.
AB  - Factor XIII is the terminal enzyme of the coagulation cascade which serves to
      rapidly crosslink the adjacent gamma-chain C-termini of fibrin clots. In vivo,
      this process is initiated by the proteolytic action of thrombin which
      simultaneously converts both soluble fibrinogen to fibrin and activates zymogen
      FXIII; fibrin then spontaneously polymerizes to form a gel which activated FXIII
      stabilizes through crosslinking. Due to the kinetic complexity and the difficulty
      of investigating gel phase reactions, methods employing pre-activation of
      recombinant human Factor XIII (rFXIII[A'2]) were developed to effectively
      decouple these reactions. By utilizing these methods, the kinetic parameters of
      gamma-chain crosslinking in fibrin gels could be determined by both initial rate
      and integrated rate techniques under physiologically relevant conditions. The
      crosslinking of the gamma-chain of fibrin gels could be described by apparent
      Michaelis kinetics with K(m)(app) = 6.2 microM, kcat = 1872 min-1, and Ksp = 302
      min-1 microM-1 for a fibrin gamma-chain monomer of M(r) = 170000 Da. In contrast,
      both the crosslinking rates of alpha-chains within fibrin gels (Ksp = 0.38 min-1
      microM-1: Bishop et al. (1993)) and the crosslinking of a soluble synthetic
      peptide containing the unique gamma-chain fibrin crosslinking site (Ksp = 0.030
      min-1 microM-1) could not be shown to saturate and gave apparent first-order
      rates with respect to rFXIII[A'2]. These observations coupled with the large
      differences in the turnover rates (approximately 10(4)) suggest two likely
      mechanisms for FXIII[A'2]-substrate interactions: (1) random (or independent)
      binding of non- or weakly interacting substrate pairs imposes a high entropic
      barrier (i. e., delta Gbinding) to the formation of a productive catalytic
      complex, e.g., for soluble gamma-chain peptides and the flexible alpha-chains
      within fibrin, and (2) binding to an oriented substrate pair effectively lowers
      the entropic barrier to formation of a Michaelis complex and thus greatly
      enhances the rate of catalysis, e.g., for gamma-chain pairs within the fibrin
      fibrils.

PMID- 9033389
TI  - DNA-damaging enediyne C-1027 inhibits initiation of intracellular SV40 DNA
      replication in trans.
AB  - This study used 2-D agarose gel techniques to examine the effects of the DNA
      strand scission enediyne C-1027 on DNA replication in SV40-infected BSC-1 cells.
      Replication of SV40 DNA was inhibited by C-1027 to a greater extent than was BSC
      1 genomic DNA replication in infected cells. Low nanomolar concentrations (0.2-10
      nM) of C-1027 affected a rapid, progressive decrease in SV40 replication activity
      and replication intermediates (RIs) within 15 min after drug addition. A
      concurrent decrease in the signal of both the SV40 bubble arc and replication
      activity with increasing concentrations of C-1027 suggested that C-1027 inhibited
      initiation of new RIs. Additionally, the reduction in bubble arc signal observed
      with C-1027 was prevented when elongation of nascent chains was blocked by
      aphidicolin. Thus, the C-1027-induced disappearance of RIs probably is related to
      the maturation of preformed replication molecules in the absence of initiation of
      new RIs. Strand damage to SV40 DNA was barely detectable at concentrations where
      inhibition of replication activity was nearly complete, indicating that C-1027
      replication inhibition occurs in trans.

PMID- 9033390
TI  - Role of the heme propionates in the interaction of heme with apomyoglobin and
      apocytochrome b5.
AB  - The heme propionate groups of both myoglobin (Mb) and cytochrome b5 form hydrogen
      bonds with nearby surface amino acids residues that are believed to stabilize the
      heme-protein complex. To evaluate the magnitude of this stabilization, the
      kinetics of heme dissociation from variants of horse heart Mb and cytochrome b5
      in which these hydrogen bonding interactions have been systematically eliminated
      were studied by the method of Hargrove and colleagues (1994), and their thermal
      stability was assessed. Elimination of each hydrogen bond was found to decrease
      the thermal stability of the proteins and increase the rate constant for heme
      dissociation in a progressive fashion. For the Mb derivatives, 1H-NMR studies
      indicate that the elimination of individual hydrogen bonds also affects the rate
      at which the heme orientational equilibrium is achieved. In both types of
      kinetics experiment, the effects of decreasing the number of potential hydrogen
      bonding interactions are found to be cumulative. Despite their kinetic effects,
      elimination of these hydrogen bonding interactions had no influence on the
      initial distribution of heme orientational isomers immediately following
      reconstitution or on the equilibrium constant of heme orientational disorder. The
      interactions between the heme propionates and nearby protein residues play a
      partial role in the stabilization of the heme-protein complex and are a major
      factor in the kinetic "trapping" of the minor heme orientation. Comparisons of
      the various rate constants determined for the mechanism of heme binding and
      reorientation suggests that the intramolecular reorientation mechanism is
      slightly favored over the intermolecular mechanism.

PMID- 9033391
TI  - Dissociation of heme from myoglobin and cytochrome b5: comparison of behavior in
      solution and the gas phase.
AB  - The relationship of the structure of a protein in solution to the structure of a
      gas-phase protein ion and the manner in which gas-phase protein ions bind small
      molecules noncovalently are topics of current debate. To address these issues,
      the stability of heme binding to wild-type and variant forms of apomyoglobin and
      apocytochrome b5 has been studied in the gas phase by electrospray mass
      spectrometry (ES-MS) and compared with the stability of heme binding to the same
      proteins in solution. The voltage required to dissociate ions of the heme-protein
      complexes in the orifice-skimmer region of an electrospray mass spectrometer, a
      measure of the complex stability, is found to be correlated with the activation
      energy for dissociation of the complexes in solution across a series of proteins
      in which the number of hydrogen bonds between the heme propionate groups and
      surface residues is systematically reduced. However, variants in which the
      hydrogen bonds to the proximal histidine have been removed are destabilized in
      solution but stabilized in the gas-phase ions. These results suggest that on the
      millisecond time scale of the ES-MS experiment, the gas-phase protein ion may
      retain much of the structure of the protein in solution, at least for those
      residues surrounding the heme group. Furthermore, the ability of ES-MS to detect
      relatively subtle differences in protein-small molecule complex stability
      demonstrated in this work suggests that this technique may be a convenient,
      sensitive, and generally useful strategy for physical characterization of such
      complexes.

PMID- 9033392
TI  - Contribution of lysine 60f to S1' specificity of thrombin.
AB  - Lys60f has been proposed to limit the S1' substrate binding site specificity of
      thrombin to small polar P1' residues by occluding the S1' binding pocket, based
      on the X-ray crystal structure of thrombin. To test this proposal, we prepared a
      Lys-->Ala (K60fA) mutant of recombinant thrombin and determined whether this
      mutation enhanced the reactivity of thrombin with a variant inhibitor
      [antithrombin (AT)-Denver] and a substrate (protein C) containing poorly
      recognized P1' Leu residues. AT-Denver in the presence of heparin inhibited K60fA
      thrombin with a second-order association rate constant [k = 4.2 +/- 0.1) x 10(5)
      M-1 s-1] that was 3.2-fold faster than thrombin [k = (1.3 +/- 0.1) x 10(5) M-1 s
      1]. Wildtype AT (P1' Ser) under the same conditions inhibited K60fA thrombin with
      a 2.5-fold slower rate constant [k = (1.1 +/- 0.1) x 10(7) M-1 s-1] than thrombin
      [k = (2.8 +/- 0.1) x 10(7) M-1 s-1]. These results indicate an overall 8.3-fold
      improvement in the recognition of the P1' Leu of AT-Denver by K60fA thrombin over
      that of wild-type thrombin; i.e., the K60fA mutation partly overcomes the defect
      in thrombin inhibition produced by the P1' mutation in AT-Denver. Resolution of
      the two-step reactions of AT and AT-Denver with wild-type and mutant thrombins
      revealed that the enhanced recognition of P1' Leu in AT-Denver by K60fA thrombin
      occurs primarily in the second reaction step in which a noncovalent AT-thrombin
      encounter complex is converted to a stable, covalent complex. Thrombin K60fA
      activated Gla-domainless protein C (GDPC) approximately 2- and approximately 4
      fold faster than thrombin in the presence and absence of thrombomodulin (TM),
      respectively, consistent with an improved interaction of the Leu P1' residue with
      the mutant S1' pocket. In contrast, the mutant thrombin clotted fibrinogen (P1'
      Gly) approximately 3-fold slower than thrombin. Kinetic analysis revealed that
      the improvement in the catalytic rate of activation of GDPC by K60fA thrombin in
      the presence of TM was localized in the second reaction step, as reflected by an
      approximately 2-fold increase in kcat. Direct binding studies showed that the
      K60fA mutation minimally affected the affinity of thrombin for Na+, indicating
      that the changes in S1' site-specificity of K60fA thrombin did not result from
      altering the allosteric transition induced by Na+. We conclude that Lys60f limits
      the P1' substrate and inhibitor specificity of thrombin by influencing the size
      and polarity of the S1' site which thereby affects the stability of the
      transition state for cleavage of the scissile bond in the second reaction step.

PMID- 9033393
TI  - Molecular design and characterization of an alpha-thrombin inhibitor containing a
      novel P1 moiety.
AB  - An inhibitor of alpha-thrombin was designed on the basis of the X-ray crystal
      structures of thrombin and trypsin. The design strategy employed the geometric
      and electrostatic differences between the specificity pockets of the two enzymes.
      These differences arise due to the replacement of Ser 190 in trypsin by Ala 190
      in thrombin. The new inhibitor contained a tryptophan side chain instead of the
      arginine side chain that is present in the prototypical thrombin inhibitors. This
      inhibitor had a Ki value of 0.25 microM, displayed more than 400-fold specificity
      for thrombin over trypsin, and doubled the rat plasma APTT at a concentration of
      44.9 microM. The X-ray crystal structure of the inhibitor/alpha-thrombin complex
      was determined. This represents the first reported three-dimensional structure of
      a thrombin/ inhibitor complex where the specificity pocket of the enzyme is
      occupied by a chemical moiety other than a guanidino or an amidino group. As was
      predicted by the molecular model, the tryptophan side chain docks into the
      specificity pocket of the enzyme. This finding is in contrast with the indole
      binding region of thrombin reported earlier [Berliner, L. J., & Shen, Y. Y. L.
      (1977) Biochemistry 16, 4622-4626]. The lower binding affinity of the new
      inhibitor for trypsin, compared to that for thrombin, appears to be due to (i)
      the extra energy required to deform the smaller specificity pocket of trypsin to
      accommodate the bulky indole group and (ii) the favorable electrostatic
      interactions of the indole group with the more hydrophobic specificity pocket of
      thrombin. The neutral indole group may be of pharmacological significance because
      the severe hypotension and respiratory distress observed following the
      administration of some thrombin inhibitors have been linked to the positively
      charged guanidino or amidino functionalities.

PMID- 9033394
TI  - Condensation of DNA and chromatin by an SPKK-containing octapeptide repeat motif
      present in the C-terminus of histone H1.
AB  - Several DNA binding motifs have been described in the C-terminus of histone H1
      (Churchill & Travers, 1991), of these the S/TPKK repeat (Suzuki, 1989) often
      occurs as a part of an octapeptide repeat of the type XTPKKXKK. We have studied
      in detail the DNA and chromatin condensing properties of a consensus octapeptide
      KSPKKAKK (8 mer) present in many histone H1 subtypes and its imperfect repeat
      ATPKKSTKKTPKKAKK (16 mer TPKK) as it occurs in the C-terminus of rat histone H1d.
      The 16 mer TPKK peptide containing two S/TPKK motifs was able to condense both
      rat oligonucleosomal (2-5 kbp) DNA and histone H1-depleted chromatin as revealed
      by circular dichroism spectroscopy. The 8 mer peptide, however, was unable to
      condense either the DNA or the histone H1-depleted chromatin. Both the 8 mer
      peptide and the 16 mer TPKK peptide displaced distamycin A from the drug-DNA
      complex, although with different efficiency, indicating that while these two
      peptides could bind DNA, only the 16 mer (TPKK) peptide could bring about
      condensation of DNA and histone H1-depleted chromatin. A mutant 16 mer (TAKK)
      peptide wherein two proline residues are replaced by alanine, was ineffective in
      bringing about condensation of both DNA and histone H1-depleted chromatin. These
      results suggest that the two beta-turn structures present in the 16 mer (TPKK)
      peptide could be important in facilitating binding to different regions of duplex
      DNA thereby bringing about close packing and condensation. The condensation
      property of the 16 mer (TPKK) peptide was very similar to that of histone H1 in
      terms of (a) its preference for AT rich DNA, (b) cooperativity of condensation,
      and (c) salt dependence of condensation. The 16 mer (TPKK) peptide, but not the 8
      mer peptide or the 16 mer (TAKK) peptide, could form complexes with a
      polynucleosomal 5S DNA core resulting in retarded mobility similar to the
      complexes formed with histone H1 on agarose gel electrophoresis.

PMID- 9033395
TI  - Functional in vivo interaction between the amino-terminal, transactivation domain
      and the ligand binding domain of the androgen receptor.
AB  - The ligand binding domain (LBD) and the amino-terminal, transactivation domain
      (TAD) of the androgen receptor (AR) were separately linked to the GAL4 DNA
      binding domain (DBD) and to the GAL4(TAD). Resulting constructs were tested in
      the yeast two-hybrid system for protein-protein interactions. In the presence of
      androgen [methyltrienolone (R1881) or dihydrotestosterone (DHT)] a
      transcriptionally active complex was formed, reflecting an association between
      the AR(LBD) and the AR(TAD). No interactions were found in the presence of low
      affinity ligands like estradiol (E2), promegestone (R5020), or progesterone (Pg).
      Use of the Thr-868-Ala mutated AR(LBD) in the assay resulted not only in a clear
      AR TAD-LBD interaction in the presence of R1881 and DHT but also in the presence
      of E2, Pg, and R5020, corresponding to the alteration in ligand specificity
      induced by the mutation. Coexpression of the fusion protein Gal4(DBD)AR(LBD) and
      the separate AR(TAD) also gave rise to the formation of a transcriptionally
      active complex. No interactions were found between two AR LBDs at the low
      expression level of the two components. However, LBD-LBD interaction was
      detectable by application of a high-expression vector for GAL4(TAD)AR(LBD),
      albeit at high ligand concentrations. To substantiate the observation of the AR
      LBD-TAD interaction, CHO cells were cotransfected with expression plasmids for a
      truncated AR, which lacks the TAD [AR(DBD)(LBD)], and for the separate AR(TAD).
      This resulted in stimulation of a MMTV-LUC reporter gene in the presence of R1881
      but not in the absence of hormone. This finding indicates that, like in the yeast
      system, in mammalian cells, TAD-LBD interactions are of importance for AR
      activation. In the mammalian system, a maximal AR TAD-LBD interaction was
      obtained at approximately 10-fold higher ligand concentrations than required for
      full-length AR activation. In the presence of low-affinity ligands, the AR TAD
      LBD interaction as measured by transcriptional activation was considerably weaker
      than the activity of the full-length AR. From the present results a concept of
      hormone-dependent AR activation is proposed, which requires a functional, direct
      or indirect intramolecular interaction between the TAD and the LBD.

PMID- 9033396
TI  - The in vitro assembly of the EcoKI type I DNA restriction/modification enzyme and
      its in vivo implications.
AB  - Type I DNA restriction/modification enzymes protect the bacterial cell from viral
      infection by cleaving foreign DNA which lacks N6-adenine methylation within a
      target sequence and maintaining the methylation of the targets on the host
      chromosome. It has been noted that the genes specifying type I systems can be
      transferred to a new host lacking the appropriate, protective methylation without
      any adverse effect. The modification phenotype apparently appears before the
      restriction phenotype, but no evidence for transcriptional or translational
      control of the genes and the resultant phenotypes has been found. Type I enzymes
      contain three types of subunit, S for sequence recognition, M for DNA
      modification (methylation), and R for DNA restriction(cleavage), and can function
      solely as a M2S1 methylase or as a R2M2S1 bifunctional methylase/nuclease. We
      show that the methylase is not stable at the concentrations expected to exist in
      vivo, dissociating into free M subunit and M1S1, whereas the complete nuclease is
      a stable structure. The M1S1 form can bind the R subunit as effectively as the
      M2S1 methylase but possesses no activity; therefore, upon establishment of the
      system in a new host, we propose that most of the R subunit will initially be
      trapped in an inactive complex until the methylase has been able to modify and
      protect the host chromosome. We believe that the in vitro assembly pathway will
      reflect the in vivo situation, thus allowing the assembly process to at least
      partially explain the observations that the modification phenotype appears before
      the restriction phenotype upon establishment of a type I system in a new host
      cell.

PMID- 9033397
TI  - Preferential interactions of the Escherichia coli LexA repressor with anions and
      protons are coupled to binding the recA operator.
AB  - The binding of Escherichia coli LexA repressor to the recA operator was examined
      as a function of the concentration of NaCl, KCl, NaF, and MgCl2 at pH 7.5, 21
      degrees C. The effects of pH at 100 mM NaCl were also examined. Changes both in
      the qualitative appearance of the binding isotherms and in the magnitude of the
      apparent binding affinity with changes in solution conditions suggest that
      binding of anions and protons by LexA repressor is linked to oligomerization
      and/or operator binding. Binding of LexA repressor to the recA operator in the
      presence of NaCl ranging from 25 to 400 mM at picomolar DNA concentration showed
      a broad, apparently noncooperative, binding isotherm. Binding of LexA repressor
      in NaF at the same [DNA] yielded binding isotherms with a narrow transition,
      reflecting an apparently cooperative binding process. Also, the apparent binding
      affinity was weaker in NaF than in NaCl. Furthermore, the binding affinity and
      also the apparent binding mode, cooperative vs noncooperative, were pH dependent.
      The binding affinity of LexA repressor for operator was greatest near neutral pH.
      The apparent binding mode was noncooperative at pH 7-9 but was cooperative at pH
      6 or 9.3. These observations suggest that the specific cation and anion
      composition and concentrations must be considered in understanding the details of
      regulation of the SOS system.

PMID- 9033398
TI  - Covalently linking BHLH subunits of MASH-1 increases specificity of DNA binding.
AB  - MASH-1, a member of the basic-helix-loop-helix (BHLH) family of transcription
      factors, promotes the differentiation of committed neuronal precursor cells. In
      vitro, MASH-1 displays only marginal DNA sequence specificity. We have produced a
      MASH-1 variant, MASH-GGC, by introducing the tripeptide Gly-Gly-Cys at the C
      terminal end of the BHLH domain. Under reducing conditions the properties of MASH
      GGC and of the BHLH domain of MASH-1 were very similar. Like MASH-1, reduced MASH
      GGC showed little specificity of DNA binding. CD spectroscopy revealed that both
      proteins underwent a conformational change from a largely unfolded to a mainly
      alpha-helical conformation upon binding to DNA. When the subunits of MASH-GGC
      were linked through a disulfide bond, the folded conformation was stable over a
      wide concentration range (2.5 nM to 2 microM) even in the absence of DNA.
      Oxidized MASH-GGC bound to E-box-containing sequences half-maximally at 148 nM,
      compared to 458 nM for the reduced form. Therefore, even when the change from a
      monomeric to a dimeric species was taken into account, the affinity for E-box
      containing DNA sequences was increased. Surprisingly, the apparent dissociation
      constant for the complex with DNA not containing E-box sequences was increased
      upon oxidation. Therefore, despite the large distance between the disulfide
      bridge and the protein-DNA interface, covalently linking the subunits of MASH-1
      increased the specificity of DNA binding significantly. In vivo, such an increase
      of the intrinsic DNA binding specificity might be achieved through interactions
      with other proteins of the transcriptional machinery.

PMID- 9033399
TI  - Comparative enzymatic study of HIV-1 reverse transcriptase resistant to 2',3'
      dideoxynucleotide analogs using the single-nucleotide incorporation assay.
AB  - Employing the single-nucleotide incorporation assay using a heteropolymeric RNA
      template and DNA primers, we defined enzymatic profiles of recombinant human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing a set
      of five mutations [A62V, V75I, F77L, F116Y, and Q151M] which confers resistance
      to multiple 2',3'-dideoxynucleosides (ddNs) on HIV-1. RTs containing other drug
      resistance-associated mutations were also examined. The K(m) for dNTPs, the kcat,
      and the kcat/ K(m) ratios of mutant RTs were all comparable to those of wild-type
      RT (RTwt). The processive primer extension activity of mutant RTs was also
      comparable to that of RTwt as examined in the presence of saturating
      concentrations of dNTPs and heparin. Determination of the Ki values toward 5'
      triphosphates (TP) of various ddNs [3'-azido-2',3'-dideoxythymidine (AZT), 2',3'
      didehydro-2',3'-dideoxythymidine (D4T), 2',3'-dideoxycytidine (ddC), (-)-beta-L
      2',3'-dideoxy-3'-thiacytidine (3TC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine
      (FddC), 2',3'-dideoxyadenosine (ddA), and 2'-beta-fluoro-2',3'-dideoxyadenosine
      (FddA)] and 9-(2-phosphonylmethoxyethyl)adenine diphosphate (PMEApp) revealed
      that RTA62V/V75I/F77L/F116Y/Q151M was insensitive to ddATP, AZTTP, D4TTP, FddATP,
      and ddCTP, but was sensitive to PMEApp, 3TCTP, and FddCTP. RTK65R was less
      sensitive to ddATP, FddATP, PMEApp, ddCTP, and 3TCTP, while RTM184V was less
      sensitive only to 3TCTP and ddCTP. The determination of Ki(ddNTP)/K(m)(dNTP)
      ratios showed that AZTTP, D4TTP, and ddCTP are, as substrates, as efficient for
      RTwt as their corresponding dNTPs, that ddATP, PMEApp, and 3TCTP are moderately
      efficient substrates for RTwt, and that FddATP is the least efficient substrate
      among ddNTPs examined. The observed cross-resistance of HIV-1 RT to various
      ddNTPs should reflect the alteration of RT's substrate recognition and should
      provide insights into the molecular mechanism of RT discrimination of ddNTPs from
      natural substrates.

PMID- 9033400
TI  - DNA polymerase beta: structure-fidelity relationship from Pre-steady-state
      kinetic analyses of all possible correct and incorrect base pairs for wild type
      and R283A mutant.
AB  - The kinetic parameters (kpol, Kd app) for all possible correct and incorrect
      pairing between the A, T, G, and C bases were determined for wild-type (WT) rat
      DNA polymerase beta (pol beta) and the R283A mutant under pre-steady-state
      kinetic assay conditions. The base substitution fidelities of these two proteins
      were then determined for all 12 possible mispairs representing the first complete
      fidelity analysis of polymerases using pre-steady-state kinetics. The results led
      to several significant findings: (i) For both WT and R283A, the fidelity is
      determined primarily by kpol (decreases for the incorporation of incorrect
      nucleotides) and to a small extent by Kd app (increases for the incorporation of
      incorrect nucleotides). (ii) In general, the fidelity for the Y.X (incorporation
      of dXTP opposite template dYMP) mismatch is different from that for the X.Y
      mismatch, reflecting the asymmetry of the active site. (iii) The fidelity of
      R283A is reduced in all 12 mispairs compared to that of WT. The extent of
      decrease varies from 200-fold for the A.G mispair to 2.5-fold for the T.C
      mispair. In general, the differences in fidelity between the mutant and WT are
      greater for purine.purine mismatches (up to 200-fold) than purine.pyrimidine,
      pyrimidine. purine, or pyrimidine.pyrimidine mismatches (up to 19-fold). (iv)
      Overall, the decreases in the fidelity of the R283A mutant are caused mainly by
      changes in the values of kpol; the kpol values of correct incorporations decrease
      to a greater extent for the R283A mutant with respect to WT than those of
      incorrect incorporations. With the exception of G.C, the values of Kd app for the
      WT and R283A mutant remain constant for correct pairings and vary by less than a
      factor of 4 for incorrect pairings. (v) For WT pol beta, the Kd app of G.C (8.6
      microM) is distinctly smaller than that of other correct base pairs (41-108
      microM). For the R283A mutant, the kpol of G.C is higher by a factor of 15-17.

PMID- 9033401
TI  - A kinetic and thermodynamic analysis of cleavage site mutations in the hammerhead
      ribozyme.
AB  - Two kinetically well-characterized hammerheads with different arm lengths were
      used to reinvestigate the cleavage properties of substrates with the four natural
      nucleotides at position 17, the residue 5' to the cleavage site. From experiments
      measuring substrate binding affinity, cleavage rates, and the internal
      equilibrium, free energy profiles of the reaction of all four substrates were
      constructed. Each nucleotide at the cleavage site affects the energy profile
      quite differently. Whereas C and U have the same ground state energy, U
      destabilizes the transition state by 1 kcal/mol. A destabilizes both the ground
      and transition states by 1 kcal/mol, and G stabilizes the ground state by 2
      kcal/mol and destabilizes the transition state by 4 kcal/mol. These data, along
      with experiments with the C3U mutant hammerhead, indicate that although an N3-N17
      pair can form, the contribution to the binding energy for the wild-type (C3-C17)
      hammerhead is quite small. Thus, the energetic cost of disrupting the C3-C17 pair
      is not great, consistent with several proposals that this occurs during cleavage.
      The data also suggest that the structure in the transition state involves
      different stabilizing interactions with nucleotide 17 than those that are
      observed in the ground state. Finally, the A17 hammerhead may cleave by a
      slightly different reaction pathway.

PMID- 9033403
TI  - Human fibroblast adhesion to fibrinogen.
AB  - Fibrinogen and fibrin mediate the adhesion of many cell types. In this report,
      the adhesion sites for human dermal fibroblasts on fibrinogen are identified and
      characterized. Fibroblasts showed a time- and dose-dependent adhesion to
      fibrinogen. Using a combination of synthetic peptide mimetics, monoclonal
      antibodies, and recombinant fibrinogens, two major classes of adhesive sites were
      identified. One class was RGD-dependent and involved the RGD sites in the alpha
      chain of fibrinogen. alpha V integrins present on fibroblasts appeared to mediate
      this adhesion. Inhibition studies showed that the RGD-independent site was
      blocked by an ICAM-1 antagonist peptide. Furthermore, the inhibition was additive
      with RGD peptide inhibition and accounted for essentially all of the fibroblast
      adhesion. Together, these results suggest that fibroblast adhesion to fibrinogen
      is mediated by both alpha V integrins and ICAM-1.

PMID- 9033402
TI  - Ferrocenoyl derivatives of alamethicin: redox-sensitive ion channels.
AB  - The synthesis and single-channel characterization of two redox-active C-terminal
      derivatives of alamethicin are herein described. The reduced [Fe(II)] forms of
      ferrocenoyl-alamethicin (Fc-ALM) and 1'-carboxyferrocenoyl-alamethicin (cFc-ALM)
      are shown to form voltage-dependent ion channels at cis positive potentials in
      planar lipid bilayers (PLB) with conductance properties similar to those of
      alamethicin. In situ oxidation of Fc-ALM [to Fe(III)] in the PLB apparatus causes
      a time-dependent elimination of channel openings, which can be restored by an
      increase in the transbilayer potential. In contrast, oxidation of cFc-ALM leads
      to the formation of shorter-lived channels. Pretreatment of the ferrocenoyl
      peptides with oxidizing agent alters their single-channel properties in a
      qualitatively similar manner, establishing that the changes in channel properties
      in the presence of oxidizing agents are due specifically to ferrocenoyl
      oxidation. We suggest that the redox sensitivity of these ferrocene-containing
      ion channels may be governed by a combination of the following factors: (1)
      changes in hydrophobicity; (2) alteration of peptide molecular dipole; and (3)
      alterations in tendencies toward self-association. However, oxidation induced
      changes in peptide conformation cannot be ruled out. Our results provide evidence
      that it is possible to engineer channel-forming peptides that respond to specific
      changes in the chemical environment.

PMID- 9033404
TI  - Global analysis of the acid-induced and urea-induced unfolding of staphylococcal
      nuclease and two of its variants.
AB  - We have studied the equilibrium unfolding staphylococcal nuclease and two of its
      variants, V66W and V66W', over two perturbation axes (acid-induced unfolding as a
      function of urea concentration and urea-induced unfolding as a function of pH).
      The transitions were monitored by simultaneous measurements of circular dichroism
      and fluorescence. With this multidimensional array of data (2 perturbation axes
      and 2 signals), we present a strategy of performing a global analysis, over as
      many as 12 individual data sets, to test various models for the unfolding
      process, to determine with greater confidence the pertinent thermodynamic
      parameters, and to characterize unfolding intermediates. For example, wildtype
      nuclease shows a cooperative two-state transition with either urea or pH as
      denaturant, but the global fits are improved when the model is expanded to
      include a pH dependence of the urea m value or when two distinct classes of
      protonic groups are considered. The best fit for wild-type nuclease is with delta
      G degree 0,UN = 6.4 kcal/mol at pH 7, with the acid-induced unfolding being
      triggered by protonation of three to five carboxylate groups (with possible
      contribution from His121), and with the urea m = 2.5 kcal mol-1 M-1. V66W' lacks
      the last 13 amino acids on the C-terminus, has a tryptophan at position 66, has a
      predominantly beta-sheet structure, and is less stable than the wild type. For
      V66W', delta G degree 0,UN = 1.6 kcal/mol, m = 1.2 kcal mol-1 M-1, and there are
      two or three groups responsible for acid unfolding. V66W, a full-length mutant
      with two tryptophan residues, unfolds via a three-state mechanism: native
      reversible intermediate reversible unfolded. It appears that its beta-barrel
      subdomain retains structure in the intermediate state. Assuming that the
      unfolding of V66W' and the beta-barrel subdomain of V66W can be described by the
      same thermodynamic parameters, a global analysis enabled a description of the
      alpha subdomain of V66W with delta G degree 0,IN = 2.7 kcal/mol, mIN = 1.1 kcal
      mol-1 M-1, and with the acid unfolding being triggered by protonation of a single
      group. This group has a pKa around 6 in the unfolded state, suggesting that the
      state of protonation of a histidine residue may contribute significantly to the
      stability of V66W.

PMID- 9033405
TI  - Determination of the chemical mechanism of malic enzyme by isotope effects.
AB  - Carbon-13 isotope effects have been determined for all four carbons of L-malate
      as a substrate for chicken liver malic enzyme, using either NADP or
      acetylpyridine-NADP as the other substrate. The effect of deuteration at C2 of
      malate was then used to tell whether the chemical mechanism of this oxidative
      decarboxylation was stepwise, with oxaloacetate as an intermediate, or concerted.
      With NADP, the 13C isotope effects at C3 and C4 both decrease with deuteration of
      malate, showing a stepwise mechanism, as previously determined [Hermes, J. D.,
      Roeske, C. A., O'Leary, M. H., & Cleland, W. W. (1982) Biochemistry 21, 5106
      5114]. With acetylpyridine-NADP, however, the 13C isotope effects at both C3 and
      C4 increase with deuteration of malate. While the increase at C4 could be
      explained by a secondary 13C isotope effect on hydride transfer, the increase at
      C3 proves that the chemical mechanism has changed to a concerted one, presumably
      because hydride transfer is more rate-limiting and the overall equilibrium
      constant is more favorable by 2 orders of magnitude. The transition state for
      this concerted reaction is asynchronous, however, with an intrinsic deuterium
      isotope effect of approximately 5 and a 13C isotope effect of only 1.010-1.015.
      Equilibrium 13C isotope effects for conversion of carbons 2, 3, and 4 of malate
      to pyruvate or CO2 are 1.010, 1.011, and 0.988, respectively. Measured 13C
      isotope effects at C2 of malate are slightly inverse, but no explanation for this
      is obvious. With NADP, deuterium isotope effects at C3 of 1.17 and 1.08 for di-
      and monodeuteration and an increase in the 13C isotope effect at C4 upon
      dideuteration at C3 are consistent with a stepwise mechanism with the deuterium
      isotope effect at C3 being only on the decarboxylation step. Smaller deuterium
      isotope effects of 1.03-1.04 from dideuteration at C3 with acetylpyridine-NADP
      are consistent with a concerted but asynchronous mechanism where C-C cleavage is
      not far advanced in the transition state.

PMID- 9033407
TI  - Identification of elements critical for phosphorylation of 3-hydroxy-3
      methylglutaryl coenzyme A reductase by adenosine monophosphate-activated protein
      kinase: protein engineering of the naturally nonphosphorylatable 3-hydroxy-3
      methylglutaryl coenzyme A reductase from Pseudomonas mevalonii.
AB  - The initially nonphosphorylatable 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase of Pseudomonas mevalonii (E.C. 1.1.1.88) was engineered to
      phosphorylatable forms in order to identify elements critical for phosphorylation
      of HMG-CoA reductase by AMP-activated protein kinase. P. mevalonii, mutant
      enzymes phosphorylatable by AMP-activated protein kinase were engineered by
      substituting cognate residues from the kinase recognition sequence of Syrian
      hamster HMG-CoA reductase (E.C. 1.1.1.34). Various combinations of residues 381
      391, which correspond to the kinase recognition sequence of the hamster enzyme,
      were mutated. P. mevalonii mutant enzyme R387S, in which a serine had been
      inserted at position P, which corresponds to that of the regulatory serine of the
      hamster enzyme, was only weakly phosphorylated. Genes that encoded thirty-six
      additional mutant enzymes containing various portions of the hamster kinase
      recognition sequence were constructed. Following expression, purified mutant
      enzymes were assayed as substrates for AMP-activated protein kinase. Identified
      as critical for phosphorylation was the simultaneous presence of aspartate or
      asparagine at position P+3 and of leucine at position P+4, three and four
      residues on the C-terminal side of the phosphorylatable serine, respectively. Two
      basic residues at positions P-1, P-2, or P-3 also appeared to be critical for
      phosphorylation when present in combination with aspartate or asparagine at P+3
      and leucine at P+4.

PMID- 9033406
TI  - Characterization of a recombinant pea 5-aminolevulinic acid dehydratase and
      comparative inhibition studies with the Escherichia coli dehydratase.
AB  - Pea 5-aminolevulinic acid dehydratase (ALAD) was purified 200-fold from a
      recombinant overproducing strain of Escherichia coli, yielding an octameric
      enzyme with a specific activity of 280 units mg-1. Divalent metal ions were
      essential, Mg2+, Mn2+, and Co2+ ions all supporting activity, whereas Zn2+ ions
      could not. Equilibrium dialysis and atomic absorption studies revealed two Mg2+
      ion binding sites per subunit. Pea ALAD bound the substrate 5-aminolevulinic acid
      covalently through a Schiff base at the P-site, electrospray mass spectrometry of
      the reduced enzyme-ALA Schiff base complex showing the presence of one P-site per
      subunit. The amino acid residue modified by ALA was identified by MALDI-MS and
      Edman sequencing as Lys-293, analogous to the active site Lys-247 of E. coli ALAD
      and Lys-252 of mammalian ALAD. Comparative studies of pea ALAD with E. coli ALAD
      using the inhibitors 3-acetyl-4-oxoheptane-1,7-dioic acid (AOHD) and
      succinylacetone (SA) indicated similar modes of inhibition, with the formation of
      a Schiff base complex between the inhibitors and the active site lysine. Studies
      with the ALA homolog, 4-amino-3-oxobutanoic acid (AOB), revealed that it is
      specific for the A-site of both the pea and E. coli ALADs. An interesting
      difference exists between the enzymes, however, pea ALAD being far more
      susceptible to inhibition with AOB than the E. coli enzyme. AOB bound 10 times
      better to the A-site of pea ALAD compared to the substrate, ALA. Despite the 2000
      times lower Ki of AOB for pea ALAD, no abortive Schiff base intermediate, between
      enzyme-bound ALA at the P-site and AOB bound at the A-site, could be
      demonstrated.

PMID- 9033408
TI  - Protein phosphorylation chain of a Bacillus subtilis fructose-specific
      phosphotransferase system and its participation in regulation of the expression
      of the lev operon.
AB  - The proteins encoded by the fructose-inducible lev operon of Bacillus subtilis
      are components of a phosphotransferase system. They transport fructose by a
      mechanism which couples sugar uptake and phosphoenolpyruvate-dependent sugar
      phosphorylation. The complex transport system consists of two integral membrane
      proteins (LevF and LevG) and two soluble, hydrophilic proteins (LevD and LevE).
      The two soluble proteins from together with the general proteins of the
      phosphotransferase system, enzyme I and HPr, a protein phosphorylation chain
      which serves to phosphorylate fructose transported by LevF and LevG. We have
      synthesized modified LevD and LevE by fusing a His-tag to the N-terminus of each
      protein allowing rapid and efficient purification of the proteins. We determined
      His-9 in LevD and His-15 in LevE as the sites of PEP-dependent phosphorylation by
      isolating single, labeled peptides derived from 32P-labeled LevD, LevD(His)6, and
      LevE(His)6. The labeled peptides were subsequently analyzed by amino acid
      sequencing and mass spectroscopy. Mutations replacing the phosphorylatable
      histidyl residue in LevD with an alanyl residue and in LevE with a glutamate or
      aspartate were introduced in the levD and levE genes. These mutations caused
      strongly reduced fructose uptake via the lev-PTS. The mutant proteins were
      synthesized with a N-terminal His-tag and purified. Mutant LevD(His)6 was very
      slowly phosphorylated, whereas mutant LevE(His)6 was not phosphorylated at all.
      The corresponding levD and levE alleles were incorporated into the chromosome of
      a B. subtilis strain expressing the lacZ gene under control of the lev promoter.
      The mutations affecting the site of phosphorylation in either LevD or LevE were
      found to cause constitutive expression from the lev promoter of B. subtilis.

PMID- 9033409
TI  - Use of a fluorescence spectroscopic readout to characterize the interactions of
      Cdc42Hs with its target/effector, mPAK-3.
AB  - The family of p21-activated kinases (PAKs) has been shown to contain a domain
      that can independently bind to the Ras-like proteins Cdc42Hs and Rac. We have
      expressed a 72 amino acid recombinant form of this p21-binding domain (PBD) from
      mPAK-3 in Escherichia Coli for use in structure-function studies. The protein can
      be purified on a nickel affinity resin due to a hexa-His tag that is incorporated
      onto the amino terminus of the domain. PBD binds to Cdc42Hs in a guanine
      nucleotide-dependent manner as demonstrated by a novel fluorescence assay that
      takes advantage of the spectroscopic properties of N-methylanthraniloyl (Mant)
      guanine nucleotides. Ionic strength has little effect on the affinity of PBD for
      Cdc42Hs, but alkaline pH values tend to weaken the interaction. We have shown
      that the inhibition of the GTPase activity of Cdc42Hs, as well as a previously
      undescribed inhibition of guanine nucleotide dissociation, is mediated by the PBD
      portion of the mPAK-3 molecule. These findings suggest that PBD binding alters
      the geometry of the guanine nucleotide binding site on Cdc42Hs, perhaps as an
      outcome of the target/effector molecule binding in close proximity to the
      nucleotide domain. We therefore tested if mutations in the effector region of
      Cdc42Hs (32-40), which in Ras are very close to the guanine nucleotide binding
      site, had any effect on PBD binding. Changing tyrosine 32 to lysine (Y32K)
      resulted in a small (5-fold) inhibition of PBD binding, but the very conservative
      mutation D38E yielded at least a 50-fold decrease in affinity. Finally, the
      catalytic domain of the GTPase activating protein, Cdc42-GAP, was shown to
      inhibit PBD binding in a competitive manner, indicating that this target molecule
      and the negative regulator (GAP) bind to overlapping sites on the Cdc42Hs
      molecule.

PMID- 9033410
TI  - Physician distribution: everybody's responsibility.

PMID- 9033411
TI  - Repressed memories: middle ground or no man's land?

PMID- 9033413
TI  - In praise of commonplace conferences.

PMID- 9033412
TI  - Repressed memories: middle ground or no man's land?

PMID- 9033414
TI  - The tobacco tragedy in northern Canada.

PMID- 9033415
TI  - Enforcement of codes governing pharmaceutical promotion: what happens when
      companies breach advertising guidelines?
AB  - Some or all of the promotional activities of pharmaceutical companies are
      typically governed through self-regulatory codes administered by industry
      associations. However, the conflicts between the commercial objectives and the
      ethical and scientific goals of promotion can potentially lead to serious
      weaknesses in the way in which these codes are enforced. This paper focuses on 5
      critical aspects involved in the enforcement of codes governing pharmaceutical
      promotion: mechanisms for recognizing violations, composition of monitoring
      committees, sanctions for code violations, the quantity and quality of
      information in reports issued about complaints and code violations, and the
      circulation these reports receive. The Code of Marketing Practices of the
      Pharmaceutical Manufacturers Association of Canada (PMAC) has serious weaknesses
      in all of these areas. Although the Pharmaceutical Advertising Advisory Board's
      Code of Advertising Acceptance avoids many of the deficiencies of the PMAC code,
      it, too, has weaknesses. Proposals for strengthening the enforcement of both
      codes are offered.

PMID- 9033416
TI  - Regulating pharmaceutical advertising: what will work?
AB  - As Dr. Joel Lexchin makes painfully obvious in this issue (see pages 351 to 356),
      regulatory processes governing pharmaceutical advertising in Canada and elsewhere
      are seriously compromised. However, the remedial measures Lexchin proposes are
      not sufficient. Financial sanctions against improper advertising are likely to be
      regarded by manufacturers as the cost of doing business, and any regulatory body
      that includes drug industry representatives or individuals receiving financial
      support from the drug industry cannot be genuinely independent. Moreover,
      manufacturers are now using promotional strategies that are particularly
      difficult to regulate. These include providing drugs at lower than the usual cost
      to ensure their inclusion in managed-care formularies, and using direct-to
      consumer advertising to take advantage of the public's lack of sophistication in
      interpreting scientific evidence. Our best hope of counteracting the power and
      influence of the drug industry lies in regulation by government agencies, whose
      interest is the protection of the public.

PMID- 9033417
TI  - The PMAC code of marketing practices: time for improvement? Pharmaceutical
      Manufacturers Association of Canada.
AB  - In this issue (see pages 351 to 356) Dr. Joel Lexchin proposes reforms that could
      help the Pharmaceutical Manufacturers Association of Canada (PMAC) adapt its Code
      of Marketing Practices to changing times. The PMAC code reflects the ethical
      concerns of drug manufacturers and speaks to the need for high standards in
      promotional activities. The code is a commendable beginning, but it does not go
      far enough in ensuring ethical practice. The PMAC should take this opportunity to
      address the concerns raised by Lexchin. For example, proactive assessment of
      advertising would improve the current system.

PMID- 9033418
TI  - Demonstrating social accountability in medical education.
AB  - The author considers the University of Toronto's Health, illness and the
      Community course for undergraduate medical students, described in this issue by
      Wasylenki and associates (see pages 379 to 383). Social accountability in medical
      education demands a community orientation and hence an emphasis on outreach.
      Medical schools should expand their clinical service to the community, provide
      community-based residency placements and offer continuing medical education in
      rural and regional centres. Accountability also requires community involvement in
      planning and implementing research projects. Placing students in a community
      setting as part of the curriculum is praiseworthy, but it is not sufficient to
      ensure social accountability. What is needed now is a more comprehensive
      acceptance by faculties of medicine of the mandate of community-centred learning,
      together with well-targeted funding for education and research initiatives.

PMID- 9033419
TI  - Devolving authority for health care in Canada's provinces: 1. An introduction to
      the issues.
AB  - In 9 of Canada's 10 provinces, much of the decision-making in health care has
      recently been devolved to local authorities. Provincial governments want this new
      governance structure to at least contain costs and improve service integration.
      However, there has been little evaluation of devolution to determine whether
      these and other goals are being met. Although devolved structures in the
      provinces vary somewhat with respect to the number of tiers, accountability
      mechanisms, degree of authority and method of funding, the only structural
      element that varies substantially is the scope of services under the authority of
      local boards. The real authority of the boards depends, however, on their
      negotiated compromises among 3 areas of tension: the provincial government's
      expectations, the providers' interests and the local citizens' needs and
      preferences. The boards' abilities to negotiate acceptable compromises will
      largely determine their effectiveness. This article introduces a survey of the
      members of 62 boards in 5 provinces for which the response rate was 65%, with 514
      of 791 board members responding.

PMID- 9033420
TI  - Creating community agency placements for undergraduate medical education: a
      program description.
AB  - PROGRAM OBJECTIVE: To provide first- and second-year medical students with
      stimulating learning experiences in the community. SETTING: Three hundred
      placements representing a broad array of urban community agencies providing both
      general and specialized health care services. PARTICIPANTS: All first- and second
      year medical students at the University of Toronto (n = 354). Other participants
      include staff of community agencies and tutors from the Faculty of Medicine and
      from the community. PROGRAM: The Health, illness and the Community course is
      mandatory and consists of 3 components. The first, in the first semester of first
      year, emphasizes the provision of health care in the community for individuals
      and populations. The second, in the second semester of first year, introduces a
      health promotion paradigm. The third component, throughout second year, allows
      students to engage in an in-depth study of the interconnection between a health
      problem and a social issue in a community agency setting. OUTCOMES: Students have
      expressed high levels of satisfaction with the community agency placements. The
      feedback from agencies has also been enthusiastic. Patients in the home care
      program have reported that visits by medical students are a positive experience.
      CONCLUSION: It is possible to recruit and maintain large numbers of urban
      community agencies as learning sites for medical students. It is hoped that this
      approach will help to produce socially responsive medical practitioners.

PMID- 9033421
TI  - Defining inappropriate practices in prescribing for elderly people: a national
      consensus panel.
AB  - OBJECTIVE: To develop a consensus-based list of inappropriate practices in
      prescribing for elderly people. DESIGN: Mail survey of a 32-member national
      panel. SETTING: Academic medical centres across Canada. PARTICIPANTS: Thirty-two
      specialists selected arbitrarily, including 7 clinical pharmacologists, 9
      geriatricians, 8 family practitioners and 8 pharmacists. OUTCOME MEASURES:
      Consensus that the practice would introduce a substantial and significant
      increase in the risk of serious adverse effect and is common enough that its
      curtailment would decrease morbidity among elderly people, ranking of clinical
      importance of the risk, and availability of equally or more effective and less
      risky alternative therapy. RESULTS: The 32-member national panel developed a list
      of 71 practices in prescribing for elderly people and rated the clinical
      significance of each on a scale of 1 (not significant) to 4 (highly significant).
      The practices in prescribing identified fell into 3 categories: drugs generally
      contraindicated for elderly people, drug-disease interactions and drug-drug
      interactions. The mean significance rating was greater than 3 for 39 practices.
      For each practice, alternative therapies were recommended. There was surprising
      congruence among the specialists on the significance rating and the suggested
      alternative therapies. CONCLUSION: The authors have developed a valid, relevant
      list of inappropriate practices in prescribing for elderly people, to be used in
      a practice-based intervention study.

PMID- 9033422
TI  - Resource allocation and physician liability.
AB  - Lawyer Karen Capen says funding cutbacks that have affected the services
      physicians can provide may cause legal problems for Canada's doctors. If cutbacks
      affect the care that is being provided, they should be discussed with the patient
      and noted on the chart. She says physicians have "good reason to be concerned"
      about increasing pressures that create an imbalance between health care resources
      and the demand and need for services. For some doctors, these have resulted in
      court cases.

PMID- 9033423
TI  - Surviving breast cancer. An emergency physician faces the fight of her life.

PMID- 9033424
TI  - A new source of Escherichia coli infection.

PMID- 9033425
TI  - Life at McGill: trying to remain optimistic while living in separation's shadow.
AB  - Spokespersons for McGill University's medical school say they have experienced
      only minor recruitment problems because of the province's ongoing threats to
      separate. David Spurgeon reports on the impact the politics of separation is
      having on medical life at McGill.

PMID- 9033426
TI  - Abortion and our changing society.

PMID- 9033428
TI  - Issues concerning ethical conduct and genetic mapping raised at Montreal meeting.
AB  - Ethical concerns about the Human Genome Diversity Project were discussed in
      Montreal last year during the 1st International Conference on DNA Sampling and
      Banking. This article, the second in a 2-part series, looks at the potential for
      misuse and commercialization of DNA samples and discusses some of the ethical
      concerns surrounding genetic mapping.

PMID- 9033427
TI  - CMA leads drive to improve physicians' management skills.
AB  - The Physician Manager Institute, developed 12 years ago by the CMA and the
      Canadian College of Health Service Executives, provides training that is designed
      to improve physicians' management and leadership skills. Changes within health
      care are prompting more doctors to seek this training in order to become managers
      within a reformed health care system.

PMID- 9033429
TI  - Study questions whether equalization of health care services a logical goal.
AB  - Ontario is in the midst of major health care reform, and one of the goals is to
      equalize the care available across the province. The authors of a study on the
      health status of people living in Southwestern Ontario question whether
      equalization is a wise goal, given that some areas face more serious health
      problems than others. Dr. Evelyn Vingilis, one of the authors, said government
      calls for standardization of health care delivery run "completely contrary" to
      the requirements of a needs-based system.

PMID- 9033430
TI  - Statement of principles: the sale and use of data on individual physicians'
      prescribing. Canadian Medical Association.
AB  - The CMA believes that prescribing data that identify individual physicians should
      be used in a manner that does not breach the privacy of patients or of physicians
      in their personal or professional lives. To address this concern, the CMA has
      developed the following set of principles for the compilation, sale and other
      commercial use of data on individual physician prescribers.

PMID- 9033431
TI  - CMA conference to look at role research plays when critical policy decisions are
      being made.
AB  - Physician leaders will meet in Ottawa Feb. 28 and Mar. 1 for the CMA's 9th Annual
      Leadership Conference to examine how evidence, research and data influence health
      policy. For information or to register contact CMA Meetings and Travel
      Department, 800 663-7336, ext. 2274; fax 613 731-8047.

PMID- 9033433
TI  - American Academy of Allergy, Asthma and Immunology, the American Association of
      Immunologists, Clinical Immunology Society joint meeting. San Francisco,
      California, February 21-26, 1997. Abstracts.

PMID- 9033434
TI  - The Asthma Action Plan: at the fulcrum of individualized asthma care.

PMID- 9033432
TI  - Treating respiratory infections in the elderly: current strategies and
      considerations.

PMID- 9033435
TI  - Take control of high-cost asthma.

PMID- 9033436
TI  - Residual abnormalities of pulmonary function in asymptomatic young adult
      asthmatics with childhood-onset asthma.
AB  - We investigated the pulmonary function of male asthmatics with childhood-onset
      asthma. Our results revealed that adult asthmatics with mild symptoms apparently
      have abnormal pulmonary function. On the other hand, after a 3-6-month symptom
      free period, and even after inhalation of bronchodilator, they still showed
      significant residual abnormalities in pulmonary function. Pulmonary function
      tests are very sensitive tools for the assessment of airway limitations during an
      acute asthmatic attack. However, these tests are not sensitive enough to detect
      residual abnormalities in asymptomatic asthmatics. Although the positive
      predictive rate for detecting small airway dysfunction in asymptomatic asthmatics
      is not high, FEF25-75 proved to be the best (63.2%) among the conventional
      pulmonary function parameters. We therefore suggest using FEF25-75 instead of
      FEV1 or peak flow rate in clinical practice for the conventional assessment of
      effectiveness of treatment, especially in the follow-up of asthmatic patients.
      More sensitive and simple tests are required in the future for detection of small
      airway dysfunction in asymptomatic asthmatics. Moreover, strict and early
      treatment of this abnormality with steroids is mandatory to prevent the formation
      of sequelae.

PMID- 9033437
TI  - Prevalence of allergic diseases and influencing factors in primary-school
      children in the Ankara Region of Turkey.
AB  - We have studied the prevalence of atopic disease, by questionnaire, in 3024
      primary-school children from three different socioeconomic levels in Ankara.
      Physical examinations were also performed on these children. The cumulative
      prevalence of asthma, allergic rhinitis, allergic conjunctivitis, and atopic
      eczema was 6.9%, 11.7%, 4.6%, and 2.6%, respectively. Allergic rhinitis was more
      common in children older than 10 years. Most of the symptoms of asthmatic
      patients began in the first 3 years of life. The cumulative prevalence of
      allergic diseases was 23.4%. This study has estimated the prevalence of allergic
      diseases, including asthma, allergic rhinitis, allergic conjunctivitis, and
      allergic dermatitis, in the Ankara region of Turkey.

PMID- 9033438
TI  - The Revised Asthma Problem Behavior Checklist: adaptation for use in Spanish
      asthmatic patients.
AB  - Behavioral problems associated with asthma management were examined in a group of
      100 adult Spanish outpatients with asthma (57 women, 43 men; 17-69 years of age).
      All of them completed a Spanish version of the Revised Asthma Problem Behavior
      Checklist (RAPBC). Data about duration, severity, and self-management of asthma
      (self-efficacy expectancies and health care utilization), as well as dyspnea and
      FEV1, were also recorded. The highest-reliability Cronbach alpha indices were for
      the criteria related to emotions and behaviors that could precipitate asthma
      attacks. Concurrent criterion validity was examined first by Pearson correlations
      between the RAPBC scores and clinical data about asthma (duration, FEV1, and
      dyspnea), and second, by examining the differences in RAPBC scores (ANOVAs) among
      three severity groups of patients. Severe patients reported more behavioral
      problems associated with poor life-styles and self-management of their asthma and
      showed more psychological and physical negative consequences related to asthma.
      In conclusion, while the RAPBC could be considered a valid instrument to assess
      the behavioral problems associated with asthma in Spanish patients, and shows a
      good concurrent criterion validity, its reliability (internal consistency) with
      respect to life-style and self-management behaviors related to asthma should be
      improved, to ensure its utility as a screening instrument for behavior-related
      problems in asthmatic Spanish patients.

PMID- 9033439
TI  - A one-week dose-ranging study of inhaled salmeterol in children with asthma.
AB  - This was a 1-week study evaluating the safety and efficacy of two dosage regimens
      of salmeterol in children with asthma. A total of 243 children, aged 4-11 years,
      with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo
      controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21
      micrograms and 42 micrograms administered via metered-dose inhaler (MDI) twice
      daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief
      of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could
      be continued during the study, but theophylline and oral beta-agonists were not
      allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial
      peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of
      treatment; morning and evening PEFR were recorded each day prior to inhalation of
      the study drug. Safety was assessed by monitoring adverse events, clinical
      laboratory values, vital signs, electrocardiogram (ECG), and 24-hr ECG (Holter)
      monitoring. Both the 21-micrograms and 42-micrograms doses of salmeterol produced
      significantly greater bronchodilation, as measured by 12-hr serial forced
      expiratory volume in 1 sec (FEV1) (p < or = 0.02) and PEFR (p < or = 0.001), than
      did placebo on days 1 and 8. A small dose-response was observed, with the 42
      micrograms dosage producing consistently higher serial FEV1 and PEFR than did the
      21-micrograms dosage, although the differences were not statistically
      significant. Morning and evening PEFR increased significantly (p < or = 0.008)
      with both dosages of salmeterol compared with placebo. Twelve patients (5%)
      experienced potentially drug-related adverse events, with headache (4% in each
      salmeterol group) being the most common. There were no clinically significant
      changes in heart rate as measured by Holter monitoring, ECGs, vital signs, or
      clinical laboratory values following treatment with either dose of salmeterol.
      Salmeterol 21 micrograms or 42 micrograms twice daily was effective in producing
      bronchodilation in children aged 4-11 years, and both dosages had good safety
      profiles. Patients treated with salmeterol 42 micrograms twice daily showed a
      trend toward greater improvement in asthma control compared with those who
      received salmeterol 21 micrograms.

PMID- 9033440
TI  - Comparison of oral bambuterol and terbutaline in elderly patients with chronic
      reversible airflow obstruction.
AB  - Bambuterol, a carbamate prodrug of terbutaline, is the first once-daily oral beta
      2-agonist. The effect/side effect ratio of bambuterol oral solution was compared
      with terbutaline mixture in elderly patients with chronic reversible obstructive
      airways disease. The study was of a double-blind, crossover, randomized design
      and consisted of a 4-7-day run-in period followed by four consecutive treatment
      periods each of 2 weeks. The treatments were bambuterol solution 20 mg nocte
      (B20), 10 mg nocte (B10), terbutaline mixture 3 mg t.i.d., (T), and placebo
      solution (P). Patients measured daily peak expiratory flow rate (PEFR), asthma
      symptoms, use of inhaled beta 2-agonist, and tremor. Of 84 patients, 66 completed
      all periods. Mean age was 67 years (60-90), basal FEV1 1.49 L, and reversibility
      of FEV1 30%. Ninety-four percent of the patients used inhaled/oral steroids in
      constant dosage. All treatments were significantly more effective than placebo.
      B20 resulted in higher morning PEFR than T (306 +/- 2.9 L/min vs. 297 +/- 2.9
      L/min), while B10 gave equivalent results to T. No differences were seen in the
      use of inhaled beta 2-agonist. Less shortness of breath was experienced during
      the night with B20 and during the day with B10 compared with placebo. Both B20
      and T produced more tremor than B10 and P. In elderly patients with chronic
      reversible airways obstruction once-daily bambuterol (10-20 mg) has a better
      effect/side effect ratio than 3 mg terbutaline thrice daily.

PMID- 9033441
TI  - Short-term regular beta 2-adrenergic agonists treatment is safe in mild
      asthmatics taking low doses of inhaled steroids.
AB  - Regular treatment with beta 2-adrenergic agonists is controversial in bronchial
      asthma. To investigate whether beta 2-adrenergic agonists can be used safely if
      associated with low doses of inhaled steroids, for a short period, without a
      deterioration of asthma control, we have examined 24 mild asthmatics. In a
      parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out
      period framed 3 weeks of treatment. All patients received inhaled beclomethasone
      dipropionate (BDP 250 micrograms t.i.d.); after 1 week, 12 patients inhaled 400
      micrograms of broxaterol and 12 patients received placebo t.i.d. FVC, FEV1, PD20
      FEV1 methacholine, morning and evening PEF, and PEF amplitude % mean were
      measured before, during, and after treatment. No significant changes were noted
      in patients receiving inhaled broxaterol. There were no differences in symptoms
      and the use of rescue medication (salbutamol spray). We conclude that short-term
      regular treatment with beta 2-adrenergic agonists is not associated with a
      deterioration in asthma control in mild asthmatics inhaling low doses of
      steroids.

PMID- 9033442
TI  - An epidemiological study of asthma prevalence and related factors among young
      adults.
AB  - Asthma and related factors were assessed by mailed questionnaires among 2041
      young adult participants in a smoking prevention project in California in 1993.
      Hispanics had lower prevalence of physician-reported asthma when compared to
      blacks and whites. Blacks were significantly more likely to be hospitalized or
      visit emergency rooms because of asthma or wheezing. After adjusting for sex,
      race, and educational level, family history of asthma was strongly associated
      with subjects' asthma (odds ratio = 3.1, 95% CI: 2.4-4.3 for physician-reported
      asthma; OR = 3.3, 95% CI: 2.4-4.5 for current asthma). Exposure to parental
      smoking (both parents smoked more than half a pack of cigarettes a day) during
      childhood (reported when participants were in grade 7) was significantly
      associated with physician-reported asthma (OR = 2.9, 95% CI: 1.6-5.6) and current
      asthma (OR = 3.3, 95% CI: 1.7-6.4). The study also found that self-reported mold
      growth at home was significantly associated with asthma (OR = 2.0, 95% CI: 1.2
      3.2). After adjusting for cigarette smoking and demographic variables, use of
      crack cocaine was marginally significantly associated with current asthma (OR =
      2.3, 95% CI: 1.0-5.2), but not with physician-reported asthma (OR = 1.5, 95% CI:
      0.7-3.3).

PMID- 9033443
TI  - Assessing the family asthma management system.
AB  - The importance of "self-management" has been increasingly recognized in the
      treatment of asthma. In the case of childhood asthma, such management must be
      accomplished by the family system, including the caregivers, the asthmatic child,
      and the alternate caregivers in collaboration with the health care providers.
      This paper presents an assessment tool, the Family Asthma Management System Scale
      (FAMSS), for evaluating the effectiveness of the family asthma management system.
      The scale is internally consistent and has excellent interrater reliability. The
      FAMSS score, together with an asthma severity measure, jointly accounted for a
      significant portion of the variance when predicting the functional severity of
      asthma experienced by this group of children.

PMID- 9033444
TI  - Focal infection.

PMID- 9033445
TI  - IR and NMR analyses of hardening and maturation of glass-ionomer cement.
AB  - It has been reported that the silicate phase as well as the cross-linking of the
      polycarboxylic acid by aluminum and calcium ions played an important role in the
      hardening of glass-ionomer cement. The objective of this study was to investigate
      the structural change during hardening of the cements by means of infrared (IR)
      spectroscopy and solid-state nuclear magnetic resonance (NMR) spectroscopy and to
      confirm the role of the silica phase in the hardening of the cement. For that
      purpose, we measured the change in compressive strength of an experimental glass
      ionomer cement, two commercial glass-ionomer cements, and a polycarboxylate
      cement and carried out 29Si and 27Al NMR analyses of the cement samples after the
      strength measurement. In the IR spectra during hardening, a characteristic band
      of the silicate network around 1000 cm-1 shifted toward high frequency with time.
      The spectrum after hardening was similar to that for a hydrated amorphous silica
      structure. The 27Al NMR analysis showed that Al3+ ion was tetrahedrally
      coordinated by oxygen in the original glass, but a part of the Al3+ ion was
      octahedrally coordinated after hardening to form Al polyacrylate gel. The
      chemical shift of Si in the 29Si NMR spectra also changed during hardening. The
      variation in the chemical shift reflected the structural change in the silicate
      network. The initial increase in compressive strength of the cement was mainly
      caused by polycarboxylate gel formation. However, it was concluded that the
      reconstruction of the silicate network contributed to the increase in strength
      with time during the period after the gelation by cross-linking was completed.

PMID- 9033446
TI  - Effect of cubic leucite stabilization on the flexural strength of feldspathic
      dental porcelain.
AB  - Previous studies (Mackert and Evans, 1993) have shown that, when feldspathic
      dental porcelain is cooled, leucite undergoes a transformation from cubic to
      tetragonal, associated with a 1.2% volume contraction. This contraction leads to
      the formation of microcracks in and around the crystals and the development of
      tangential compressive stresses around the crystals. Our aim was to stabilize
      increasing amounts of the cubic form of leucite in a leucitereinforced dental
      porcelain, evaluate its effect on the flexural strength, and characterize its
      microstructure. The hypothesis was that in the absence of crystallographic
      transformation, the contraction of the leucite crystals would be lower, thereby
      limiting the formation of microcracks and minimizing the development of
      tangential compressive stresses around the leucite particles. We prepared 8
      porcelain compositions by mixing increasing amounts of either leucite (KAlSi2O6)
      or pollucite (CsAlSi2O6) with Optec HSP porcelain (Jeneric/Pentron Inc.,
      Wallingford, CT). Porcelain disks were made from each composition (n = 10 per
      group). X-ray diffraction analyses showed that the amount of stabilized leucite
      increased with the amount of pollucite added. The microstructure of the specimens
      containing tetragonal leucite was characterized by twinned leucite crystals,
      whereas no twinning was observed in the specimens containing cubic leucite. The
      evaluation of crack deflection showed that significantly less deflection occurred
      in the specimens containing cubic leucite. The mean biaxial flexural strength for
      the group corresponding to 22.2 wt% added pollucite, fired at 1038 degrees C, was
      significantly lower than that for the control group. The group corresponding to
      22.2 wt% added leucite fired at 1150 degrees C exhibited a mean biaxial flexural
      strength significantly higher than that of all other groups that were not
      significantly different from the control group. Overall, the stabilization of
      cubic leucite reduced the flexural strength and the number of crack deflections
      in leucite-reinforced porcelain. Apparently, the development of tangential
      compressive stresses around the leucite crystals when cooled is responsible for a
      significant amount of strengthening of feldspathic dental porcelain.

PMID- 9033448
TI  - Prediction of secondary caries around tooth-colored restorations: a clinical and
      microbiological study.
AB  - Caries at the margins of restorations is difficult to diagnose, and the relevance
      of staining and ditching around tooth-colored fillings is unclear. This clinical
      study questions the relevance of marginal color change and marginal ditching to
      the level of infection of the dentin beneath the margins of tooth-colored
      restorations. Clinically visible sites (197) on the tooth/restoration margin were
      selected in 113 teeth. The filling margin and the enamel adjacent to each site
      were noted as stained or stain-free, and sites were graded as intact, having a
      narrow ditch, or having a wide ditch. Thirty sites with frankly carious lesions
      were also included. Plaque was sampled at the tooth-restoration margin and the
      filling removed. The enamel-dentin junction (EDJ) at each sample site was noted
      as hard or soft when probed, and the dentin was sampled. Samples were vortexed,
      diluted, and cultured for total anaerobic counts, mutans streptococci, and
      lactobacilli. There were more bacteria in the plaque over frankly carious
      cavities, and the dentin was soft and heavily infected. Only 38 out of 167 sites
      without frankly carious cavities had soft dentin at the EDJ. Both the plaque and
      dentin in these sites harbored more micro-organisms. However, none of the
      clinical criteria chosen would reliably predict the presence of this soft dentin.
      In this study, only a frankly carious lesion at the margin of the filling
      constituted a reliable diagnosis of secondary caries.

PMID- 9033447
TI  - Protein characterization of fluorosed human enamel.
AB  - Despite extensive investigation, the development mechanism or mechanisms
      resulting in dental fluorosis are unknown. Several hypotheses suggest abnormal
      matrix synthesis, secretion, and delayed and/or defective matrix degradation with
      retention of enamel protein. The purpose of this study was to characterize the
      protein composition of fluorosed human enamel. Nine permanent moderately
      fluorosed (developed in a 3.2 ppm H2O area) and ten permanent normal control
      teeth (from individuals with < 0.2 ppm F in their drinking water) were evaluated.
      The enamel fluoride concentration, protein content, and amino acid composition
      were determined for each tooth. The enamel proteins were further characterized by
      gel electrophoresis and by Western blot analysis by means of polyclonal
      antibodies raised against recombinant amelogenin protein. Fluorotic enamel had
      significantly elevated (p = 0.0001) F levels compared with normal enamel (mean [F
      ] fluorosed = 431 ppm; mean [F-] control = 62 ppm). While there was a
      significantly greater protein content by weight in fluorosed enamel compared with
      normal enamel (mean fluorosed = 0.27%; mean control = 0.11%), the amino acid
      profiles were similar for fluorosed and normal enamel. Gel electrophoresis showed
      fluorosed enamel to have a greater diversity of primarily low-molecular-weight
      proteins compared with normal enamel. Western blot analysis did not indicate
      retention of amelogenin in either fluorosed or normal enamel. This investigation
      showed that the protein content of fluorosed enamel was greater than that of
      normal enamel; however, the amino acid compositions were similar for fluorosed
      and normal enamel. Furthermore, there does not appear to be retention of
      significant amounts of amelogenin in fully mature, moderately fluorosed human
      enamel. Although delayed removal of the enamel matrix proteins may play a role in
      the hypomineralization defects seen in fluorosed enamel, the majority of these
      proteins are absent in the mature tissue of these moderately fluorosed teeth.

PMID- 9033450
TI  - Tongue volume in human female adults with mandibular prognathism.
AB  - It has often been hypothesized that a large tongue leads to an enlargement of the
      mandible and therefore contributes to the development of mandibular prognathism.
      We examined (1) whether the tongue volume in human subjects with mandibular
      prognathism was larger than that in subjects with good occlusion and (2) whether
      the tongue volume and the pharyngeal capacity correlated with the morphological
      characteristics of dento-skeletal structures. Magnetic resonance images of the
      tongue and its surrounding structures were recorded for female adult volunteers
      with good occlusion (control group, n = 10) and patients with mandibular
      prognathism (test group, n = 16). Lateral cephalograms were obtained for the
      patients. No significant differences were determined for the tongue volume or the
      pharyngeal capacity between the two groups. The tongue volume did not correlate
      with the pharyngeal capacity (r = 0.280, p = 0.166). The tongue volume correlated
      with the facial angle (r = 0.548, p = 0.028), the Y-axis (r = 0.539, p = 0.031),
      and the angle nasion-A point-pogonion (r = 0.540, p = 0.031). These results
      suggest that the tongue volume is accounted for by the combined horizontal and
      vertical location of the chin and symphysis, but do not support the conventional
      clinical surmise that large tongue volume is inherent in patients with mandibular
      prognathism.

PMID- 9033449
TI  - The estimation of caries prevalence in small areas.
AB  - National surveys have been effective for the estimation of caries prevalence in
      broad regions of the US. However, it is unclear if data from such surveys can be
      used to estimate prevalences in small areas such as states or counties because of
      small sample sizes within individual areas. In this study, we applied specialized
      statistical methods to the estimation of small-area caries measures using data
      from an oral health survey conducted in the State of Washington. Dental exams to
      assess caries and the presence of sealants and fluorosis were performed on 2921
      third-grade students in 84 public schools selected by a stratified random sample
      from all 39 counties in the state. Statistical methods for small-area estimation
      were used to estimate disease and sealant utilization measures for each of the
      counties. Adjustment was made for covariates measured at the school level,
      including ethnicity and the proportion of children in the Federally sponsored
      school lunch program. Substantial variability in disease and sealant utilization
      between counties was found. The estimated number of decayed and filled surfaces
      per child was 4.7 (inter-county range, 2.4 to 7.4). The estimated number of
      surfaces of untreated decay was 1.2 per child overall (range, 0.5 to 3.1). Thirty
      percent of the children had restorative treatment needs (range, 15 to 54%). The
      prevalence of sealants on one or more permanent molars was estimated to be 34%
      (range, 19 to 46%). Overall, only 8% of children showed evidence of fluorosis.
      The results demonstrate the usefulness of small-area estimation methods for oral
      health surveys.

PMID- 9033451
TI  - An ultrastructural study of the relationship between sensory trigeminal nerves
      and odontoblasts in rat dentin/pulp as demonstrated by the anterograde transport
      of wheat germ agglutinin-horseradish peroxidase (WGA-HRP).
AB  - Because the ultrastructure of the trigeminal sensory nerves in dentin, especially
      in relation to odontoblasts, remains to be clarified, we investigated the
      relationship between the trigeminal sensory nerves and the odontoblast processes
      using the anterograde axonal transport technique by injecting wheat germ
      agglutinin-horseradish peroxidase (WGA-HRP) into the rat trigeminal ganglion.
      Light microscopically, the nerves labeled with WGA-HRP were mainly concentrated
      at the pulpal horn, forming a nerve plexus at the subodontoblastic region and
      penetrating the predentin/dentin about 50 to 70 microns. Ultrastructurally, HRP
      reaction products were observed intra-axonally in the myelinated (A delta) and
      unmyelinated (C) axons in the subodontoblastic region. Most nerves lost the
      Schwann sheath and were naked in the predentin/dentin. The labeled varicosities
      were close to the odontoblast processes in the dentinal tubules. No synaptic
      structures could be detected between the varicosities and the odontoblasts, but a
      gap about 20 nm wide was found between them. One type of varicosity was a rich
      mitochondria-containing varicosity, while the other was a rich vesicle-containing
      (large dense core vesicles and small clear vesicles) one. The reaction products
      were also found in the extracellular spaces surrounding the axons. Sometimes the
      reaction products were seen in the coated pits or the endocytotic vesicles of the
      odontoblast processes. The present study demonstrated that nerve endings
      (varicosities) derived from the trigeminal ganglion were present in the dentinal
      tubules, and that WGA-HRP extracellularly extruded from the sensory nerves in the
      odontoblastic layer or predentin/dentin. These findings thus suggest that sensory
      nerves may have some (e.g., trophic) effect on either odontoblasts or the
      environment around the sensory nerves in the dentin/pulp.

PMID- 9033452
TI  - An in vitro model of human dental pulp repair.
AB  - Pulp tissue responds to dentin injury by laying down reactionary dentin secreted
      by existing odontoblasts or reparative dentin elaborated by odontoblast-like
      cells that differentiated from precursor cells in the absence of inner dental
      epithelium and basement membrane. Furthermore, growth factors or active dentin
      matrix components are fundamental signals involved in odontoblast
      differentiation. In vitro, dental pulp cells cultured under various conditions
      are able to express typical markers of differentiation, but no culture system can
      re-create pulp response to dentin drilling. This paper reports the behavior of
      thick slices from human teeth drilled immediately after extraction and cultured
      from 3 days to 1 month. Results show that the damaged pulp beneath the cavity is
      able to develop, in vitro, some typical aspects correlated to tissue healing,
      evidenced by cell proliferation (BrdU-positive cells), neovascularization
      (positive with antitype-IV collagen antibodies), and the presence of functional
      (3H proline-positive) cuboidal cells close to the injured area. After 30 days of
      culture, elongated spindle-shaped cells can be seen aligned along the edges of
      the relevant dentin walls, whereas sound functional odontoblasts are well
      preserved beneath healthy areas. This tissue recovery leads us to believe that
      such a culture model will be a useful system for testing factors regulating pulp
      repair.

PMID- 9033453
TI  - Reactivity of Candida albicans germ tubes with salivary secretory IgA.
AB  - Salivary secretory IgA (sIgA) has been shown to react with a group of heat shock
      mannoproteins preferentially expressed on yeast cells grown at 37 degrees C.
      Since at this temperature C. albicans can induce germ tubes, we explored the role
      of germ tube induction on human salivary sIgA reactivity in both germinative and
      agerminative C. albicans strains, in an attempt to investigate whether the germ
      tube expressed the heat shock mannoproteins reactive with sIgA. The reactivity
      with sIgA of the agerminative strain, grown at 25 and 37 degrees C for different
      times, was measured spectrofluorometrically and was fairly constant with time.
      Yeast cells grown at 37 degrees C tended to be more reactive than those grown at
      25 degrees C. In contrast, when compared with the yeast cells of the germinative
      strain grown at 25 degrees C, there was a statistically significant decrease in
      reactivity with sIgA during germ tube formation. Serum IgA and IgG did not show
      statistically significant changes in reactivity with C. albicans during
      germination, suggesting differences in reactivity with C. albicans cell wall
      antigens between mucosal and systemic humoral responses. Cell wall mannoproteins
      of molecular masses > 60 kDa were characterized by Western blotting as
      responsible for the decrease in sIgA reactivity observed in the germ tube, and
      the fall in sIgA reactivity was related to the release of cell wall mannoproteins
      into the culture medium. The release of these mannoproteins may be a mechanism
      whereby C. albicans avoids the action of sIgA, and it may play an important role
      in the post-parasite relationship in oral candidiasis.

PMID- 9033455
TI  - Exposure of periodontal ligament cells to methyl mercaptan reduces intracellular
      pH and inhibits cell migration.
AB  - Volatile sulfur compounds such as hydrogen sulfide and methyl mercaptan have been
      associated with adult periodontitis as well as with healing surgical wounds. To
      examine the effects of these compounds on the periodontium, we assayed
      periodontal ligament (PDL) cells for changes in intracellular pH, total protein,
      and cell migration following chronic exposure to CH3SH. Intracellular pH was
      quantitated by fluorescence measurements of cells loaded with BCECF, a pH
      sensitive dye. Data show that 48-hour exposure to mercaptan lowered resting
      intracellular pH but did not consistently alter activity of the Na/H exchanger.
      This effect was seen in PDL cells from three different patients. Lowered pH was
      accompanied by decreases in both total protein and mature alpha 1 and alpha 2
      chains of type I collagen. Since reductions in intracellular pH and total protein
      have been associated with inhibition of cell motility, migration was quantitated
      by sequential computer imaging, which measured the increase in size of plated
      cell circles at different times of migration. Incubation of PDL cells in pH 7.4
      and 6.6 buffers reversibly altered intracellular pH. Migration was reversibly
      inhibited in pH 6.8 buffer. Exposure to CH3SH reduced intracellular pH in pH 7.4
      buffer and in three independent assays inhibited enlargement of cell circles in
      pH 7.4 medium. These effects were therefore not related to alterations of
      extracellular pH, which remained at 7.4. The results support the hypothesis that
      gases such as methyl mercaptan may play a role in both surgical wound healing and
      periodontal disease by adversely affecting cell function and suggest that
      alterations in intracellular pH may be part of the mechanism for these changes.

PMID- 9033454
TI  - Membrane components of Treponema denticola trigger proteinase release from human
      polymorphonuclear leukocytes.
AB  - Tissue destruction during periodontitis is believed to be primarily brought about
      by leukocyte proteinases. We postulate that oral spirochetes cause discharge of
      polymorphonuclear leukocyte (PMN) lysosomal enzymes. Effects of Treponema
      denticola 53-kDa outer membrane protein, lipopolysaccharide (LPS), and
      peptidoglycan on degranulation of matrix metalloproteinases (MMP)-8 (collagenase)
      and -9 (gelatinase), cathepsin G, and elastase by human peripheral blood PMNs
      were studied by specific enzyme assays and Western blot analysis. T. denticola 53
      kDa kDa outer membrane protein was found to be a particularly efficient inducer
      of MMP-8 release. The induction was comparable with that of phorbol myristate
      acetate, a known inducer of PMN specific granule discharge. All of the treponemal
      substances, most notably the 53-kDa protein and LPS, induced release of MMP-9, a
      component of C-type granules. Both collagenase and gelatinase released from PMNs
      were mostly in active forms. Release of cathepsin G and elastase was also
      observed with the 53-kDa protein treatment. The other T. denticola substances did
      not induce release of these serine proteinases. Lactate dehydrogenase was not
      released from PMNs by the treatments, indicating that the degranulation was
      specific and not caused by toxic effects of the substances. This was confirmed by
      transmission electron microscopy of PMNs treated with the 53-kDa protein that
      showed rapid vacuole formation and cell shape changes but no disintegration of
      the cells. Thus, T. denticola may participate in the PMN-dependent extracellular
      matrix degradation during the course of periodontal inflammation by triggering
      the secretion and activation of matrix metalloproteinases.

PMID- 9033456
TI  - Zeroing in on medication errors.

PMID- 9033457
TI  - Platelet alloantigens: cardiovascular as well as immunological risk factors?

PMID- 9033458
TI  - Should pneumococcal infections continue to be classified as a single disease?

PMID- 9033459
TI  - Increased writing activity in neurological disease.

PMID- 9033460
TI  - Developmental abnormalities in autism.

PMID- 9033461
TI  - Safety of minocycline for acne.

PMID- 9033462
TI  - Randomised, placebo-controlled trial of carvedilol in patients with congestive
      heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure
      Research Collaborative Group.
AB  - BACKGROUND: In patients with heart failure, beta-blocker therapy improves left
      ventricular function after 3-6 months of treatment, but effects of such treatment
      on symptoms and exercise performance are inconsistent, and the longer-term
      effects on death and other serious clinical events remain uncertain. We have
      investigated these issues in a double-blind, placebo-controlled, randomised trial
      of the beta-adrenergic blocker carvedilol (which also has alpha 1-blocking
      properties). METHODS: 415 patients with chronic stable heart failure were
      randomly assigned treatment with carvedilol (207) or matching placebo (208). At
      baseline, 6 months, and 12 months, we measured left-ventricular ejection
      fraction, left-ventricular dimensions, treadmill exercise duration, 6 min walk
      distance, New York Heart Association (NYHA) class, and specific activity scale
      (SAS) score. Double-blind follow-up continued for an average of 19 months, during
      which all deaths, hospital admissions, and episodes of worsening heart failure
      were documented. FINDINGS: After 12 months, left-ventricular ejection fraction
      had increased by 5.3% (2p < 0.0001) and end-diastolic and end-systolic dimensions
      had decreased by 1.7 mm (2p = 0.06) and 3.2 mm (2p = 0.001), respectively, in the
      carvedilol group compared with the placebo group. During the same period that
      were no clear changes in treadmill exercise duration, 6 min walk distance, NYHA
      class, or SAS score. After 19 months, the frequency of episodes of worsening
      heart failure was similar in the carvedilol and placebo groups (82 vs 75;
      relative risk 1.12 [95% Cl 0.82-1.53]) but the rate of death or hospital
      admission was lower in the carvedilol group than in the placebo group (104 vs
      131; relative risk 0.74 [0.57-0.95]). INTERPRETATION: The beneficial effects of
      carvedilol on left-ventricular function and size were maintained for at least a
      year after the start of treatment, but carvedilol had no effect on exercise
      performance, symptoms, or episodes of worsening heart failure. There was an
      overall reduction in events resulting in death or hospital admission, and a year
      of treatment with carvedilol resulted in the avoidance of one such serious event
      among every 12-13 (SE 5) of these patients with chronic stable heart failure.

PMID- 9033463
TI  - Familial intracranial aneurysms.
AB  - BACKGROUND: We set out to determine the prevalence of incidental intracranial
      aneurysms in first-degree relatives aged 30 years or more of people with
      intracranial aneurysms, and to see if polycystic kidney disease contributes to
      the aggregation of familial intracranial aneurysms. METHODS: 91 families with two
      or more affected members had previously been identified from a 14 year series of
      1150 intracranial aneurysm patients treated at the University Hospital of Kuopio,
      Finland. Magnetic resonance angiography was used as a preliminary screening
      method, followed by conventional four-vessel angiography to verify suspected
      aneurysms. Participants were also screened for polycystic kidneys by
      ultrasonography. FINDINGS: Incidental aneurysms were detected in 40 individuals:
      38 of 438 individuals from 85 families without polycystic kidney disease or other
      diagnosed heritable disorders, and two of 22 individuals from six families known
      to have polycystic kidney disease. The crude and age-adjusted prevalence of
      incidental intracranial aneurysms among screened first-degree relatives was 8.7
      (SE 1.3)% (95% CI 6.2-11.7) and 9.1 (1.4)% (6.2-11.7), respectively, for the
      familial group and the crude prevalence for the polycystic kidney group was 9.1
      (6.1)% (1.1-29.2). INTERPRETATION: Our results demonstrate a high prevalence of
      incidental intracranial aneurysms among first-degree relatives aged 30 years or
      older of patients with the condition and indicate that the risk of having an
      aneurysm is about four times higher for a close relative than for someone from
      the general population. Also, polycystic kidney disease families are a small
      fraction of the familial intracranial aneurysm families.

PMID- 9033464
TI  - PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial
      infarction, stroke, and venous thrombosis.
AB  - BACKGROUND: The gene encoding the platelet glycoprotein IIIa receptor (GPIIIa),
      shows polymorphism (PIA1/A2). In a previous study, men with acute coronary
      ischaemia were more likely than controls to carry the PIA2 allele. This receptor
      has an important role in acute thrombus formation; these findings therefore raise
      the possibility of inherited platelet risk factors for both arterial and venous
      thrombosis. We investigated whether the PIA2 allele is associated with myocardial
      infarction, stroke, and venous thrombosis in a large prospective cohort of men in
      the USA. METHODS: 14916 initially healthy men participating in the Physicians
      Health Study provided baseline blood specimens for DNA analysis and were followed
      prospectively for a mean of 8.6 years. 374 men had a first myocardial infarction,
      209 stroke, and 121 venous thrombosis during follow-up (704 cases). Distribution
      of the PIA1/A2 polymorphism was investigated by a PCR based on restriction
      fragment length polymorphism in these men and in a sample of 704 matched study
      participants who remained free of thrombosis during follow-up (controls).
      FINDINGS: The frequency of the PIA2 allele was similar to the control frequency
      (14.8%) among men who had myocardial infarction (13.5%, p = 0.4), stroke (13.4%,
      p = 0.5), or venous thrombosis (14.5%, p = 0.9). The relative risk of any
      vascular event among men homozygous or heterozygous for PIA2 compared with men
      homozygous for PIA1 was 0.96 (95% CI 0.8-1.2). We found no evidence of
      association between the PIA2 allele and myocardial infarction (relative risk 0.93
      [95 0.7-1.2]), stroke (0.93 [0.7-1.3]), or venous thrombosis (1.07 [0.7-1.6]).
      There was no evidence of association in subgroup analyses by age, smoking status,
      and presence of family history of premature coronary disease,
      hypercholesterolaemia, hypertension, or diabetes. Aspirin use had no effect on
      these findings. INTERPRETATION: In a large cohort of apparently healthy men,
      carriage of the GPIIIa PIA2 allele was not associated with any increase in
      subsequent risk of myocardial infarction, stroke, or venous thrombosis.

PMID- 9033465
TI  - Prospective study of CAM 17.1/WGA mucin assay for serological diagnosis of
      pancreatic cancer.
AB  - BACKGROUND: Serological tests for pancreatic cancer are little used, partly
      because such assays have proved insufficiently specific for screening. However,
      retrospective studies have reported results that compare well with commonly used
      scanning techniques. In this prospective study we assessed a new type of combined
      lectin/antibody enzyme-linked mucin assay, CAM 17.1, in a routine clinical
      setting. METHODS: Clinicians at a 1200-bed teaching hospital were encouraged to
      request the CAM 17.1 assay for any patient whose differential diagnosis included
      pancreatic cancer. Serum samples from 250 patients were tested during an 18-month
      period. Patients were followed up for at least 8 months. 75 patients who did not
      have symptoms of pancreatic cancer and had alternative diagnoses were also
      studied as a control group. FINDINGS: Of the 250 patients, 36 had pancreatic
      cancer, as defined by histological and imaging criteria, and eight of these
      patients had a resectable tumour. The sensitivity and specificity of the CAM 17.1
      assay were 86% and 91%, respectively, in all patients, 85% and 81% in those who
      presented with jaundice, and 89% and 94% in patients who did not have jaundice.
      The sensitivity of the assay compared well with that of ultrasound scanning (59%)
      and computed tomography (83%) in these patients. Use of the CAM 17.1 assay in
      combination with ultrasonography allowed identification of 94% of patients with
      pancreatic tumours and all of those with resectable tumours. CAM 17.1 binding
      activity did not correlate with tumour size. INTERPRETATION: Our study confirms
      the usefulness of the CAM 17.1 tumour-marker assay for the diagnosis of
      pancreatic cancer. Serological mucin assays should be used more widely in
      combination with ultrasonography in the investigation of non-jaundiced patients
      with unexplained abdominal pain or weight loss.

PMID- 9033466
TI  - Association of tuberous sclerosis of temporal lobes with autism and atypical
      autism.
AB  - BACKGROUND: Tuberous sclerosis (TS) is a multisystem genetic disorder that is
      associated with mental retardation, autism, and atypical autism. We investigated
      the basis for these associations by examining whether the liability to mental
      retardation and autism or atypical autism is related to the number and
      distribution of hamartomatous brain growths (cortical tubers) that characterise
      TS. METHODS: 18 patients consecutively referred to our clinic were assessed for
      the presence of autism or atypical autism, and their IQs were estimated (without
      awareness of brain-scan results). Brain scans were reviewed by a neuroradiologist
      (unaware of clinical diagnoses), and the number and location of cortical tubers
      was examined in relation to the liability to psychopathology. FINDINGS: Nine of
      the 18 patients had autism or atypical autism (two with IQ > or = 70; four with
      IQ 51-69, three with IQ < or = 50; eight with a history of epilepsy). The
      remaining patients had various other psychiatric disorders (five with IQ > or =
      70; four with IQ 51-69; seven had a history of epilepsy). In the group as a
      whole, the number of tubers was significantly greater (p = 0.005) in patients
      with mental retardation (median 6 [IQR 4-9]) than in those of normal intelligence
      (1 [0-3]), and the degree of mental retardation was significantly correlated with
      the number of brain tubers (rs = 0.64; p = 0.008). Similarly, the number of
      tubers was significantly greater (p = 0.02) in individuals with a diagnosis of
      autism or atypical autism (6 [4-8]) than in those without this diagnosis (2 [1
      4]). Eight of the nine patients with autism or atypical autism, but none of the
      non-autistic individuals, had tubers located in the temporal lobes (p = 0.0004).
      Otherwise, no particular distribution of cortical tubers was associated with a
      diagnosis of autism or atypical autism. INTERPRETATION: Our investigation
      provides evidence of an association between a gross, focal brain abnormality
      detectable on neuroimaging and autism or atypical autism. The results show the
      importance of scan findings in the prognosis of TS, and also suggest that
      temporallobe neurodevelopmental abnormalities may create a risk for autism or
      atypical autism.

PMID- 9033467
TI  - A 66-year-old man with severe angina and previous coronary artery bypass.

PMID- 9033468
TI  - Plasma homocysteine and cardiovascular disease mortality.

PMID- 9033469
TI  - Immunosuppression and risk of non-melanoma skin cancer in renal transplant
      recipients.

PMID- 9033471
TI  - Coinfection with Borrelia burgdorferi and the agent of human granulocytic
      ehrlichiosis.

PMID- 9033470
TI  - Interferon for hepatitis C.

PMID- 9033472
TI  - Worldwide pharmacovigilance systems and tolrestat withdrawal.

PMID- 9033473
TI  - Minocycline-induced oral hyperpigmentation.

PMID- 9033474
TI  - Generating evidence of a reduction in colorectal cancer mortality.

PMID- 9033475
TI  - Nitric oxide synthase inhibition in migraine.

PMID- 9033476
TI  - Increase in incidence of childhood empyema in West Midlands, UK.

PMID- 9033477
TI  - Neurological disturbances due to filgrastim.

PMID- 9033478
TI  - High-level resistance to ciprofloxacin in Escherichia coli.

PMID- 9033479
TI  - Smoking and oestrogen-replacement therapy as protective factors for Alzheimer's
      disease.

PMID- 9033480
TI  - Human scalps as a reservoir of domestic mites.

PMID- 9033482
TI  - Hypothyroidism.

PMID- 9033483
TI  - Peptide antibiotics.
AB  - The era of the "classical antibiotic" may be over. The emergence of resistance
      has seen to that. Yet no truly novel class of antibacterial agent has come on the
      market in the past 30 years. Currently there is great interest in peptide
      antibiotics, especially the cationic peptides. Thousands of such molecules have
      been synthesised and just a few are entering clinical trials. Because they kill
      bacteria quickly by the physical disruption of cell membranes, peptide
      antibiotics may not face the rapid emergence of resistance.

PMID- 9033484
TI  - The King's Fund: a century of hospital charity.

PMID- 9033485
TI  - Hospital-acquired Clostridium difficile diarrhoea and herd immunity.
AB  - Clostridium difficile diarrhoea represents a significant health-service burden.
      We recently experienced an outbreak of C difficile diarrhoea associated with
      increased use of cefotaxime. The question we pose in this paper is how did the
      introduction and withdrawal of a single antibiotic so greatly affect rates of C
      difficile diarrhoea? Other antibiotics had nearly as high a risk of causing
      diarrhoea as cefotaxime, and the majority of patients never received cefotaxime.
      We believe that such outbreaks of C difficile diarrhoea are best understood in
      terms of a population model, and that taking antibiotics like cefotaxime should
      be thought of as a population rather than an individual risk factor. We postulate
      a herd-immunity model of C difficile diarrhoea, and examine the implications of
      this hypothesis.

PMID- 9033486
TI  - Vancomycin-dependent enterococcus.

PMID- 9033487
TI  - Vancomycin-dependent enterococcus. Sensitivity plate of Pseudomonas aeruginosa
      isolated from urine.

PMID- 9033488
TI  - Vancomycin-dependent enterococcus.

PMID- 9033489
TI  - Gastric safety and enteric-coated aspirin.

PMID- 9033490
TI  - Gastric safety and enteric-coated aspirin.

PMID- 9033491
TI  - Gastric safety and enteric-coated aspirin.

PMID- 9033492
TI  - Gastric safety and enteric-coated aspirin.

PMID- 9033493
TI  - Oestrogen replacement in prevention of coronary heart disease.

PMID- 9033494
TI  - WOSCOPS. West of Scotland Coronary Prevention Group.

PMID- 9033495
TI  - Feeding tubes in prevention of pneumonia.

PMID- 9033496
TI  - Presentation of Whipple's disease.

PMID- 9033497
TI  - Immunotherapy for HIV.

PMID- 9033498
TI  - MALT lymphoma.

PMID- 9033499
TI  - GB virus C transmission by blood products.

PMID- 9033500
TI  - Missed clues and delayed diagnosis of immunodeficiency.

PMID- 9033501
TI  - Training of doctors in the UK.

PMID- 9033502
TI  - Training of doctors in the UK.

PMID- 9033503
TI  - Training of doctors in the UK.

PMID- 9033504
TI  - Provisional registration of useful treatments.

PMID- 9033505
TI  - Poliomyelitis vaccination strategies for Europe.

PMID- 9033507
TI  - Down's syndrome screening with nuchal translucency.

PMID- 9033506
TI  - Poliomyelitis vaccination strategies for Europe.

PMID- 9033508
TI  - Sleeping sickness in Zaire.

PMID- 9033509
TI  - Association of insulin-like growth factor-I with body composition, weight
      history, and past health behaviors in the very old: the Framingham Heart Study.
AB  - OBJECTIVES: We examined correlates of insulin-like growth factor-I (IGF-I), an
      indicator of growth hormone levels, to identify factors associated with higher
      levels of IGF-I in old age. DESIGN: Nested study of cross-sectional correlates
      and early-life predictors of IGF-I level. SETTING: A longitudinal cohort study,
      the Framingham Heart Study. PARTICIPANTS: A total of 790 men and women (mean age
      78.5, range 72-94), who had weight, waist and hip circumferences measured at the
      time of IGF-I measurement. MEASUREMENTS: Association of IGF-I with weight, fat
      distribution, functional status, nutritional indicators, and past health
      behaviors was assessed. We also examined IGF-I in relation to body composition
      derived from dual energy X-ray absorptiometry. RESULTS: IGF-I levels declined
      with age in both men and women. However, low IGF-I did not show expected
      associations with low lean mass and increased body fat. Current functional status
      and grip strength were not associated with IGF-I Low IGF-I was associated with
      weight loss in men; the strongest associations were with indicators of poorer
      nutritional status in both men and women. Levels of IGF-I in old age did not vary
      by past health behaviors. CONCLUSION: Although IGF-I declined with age, these
      data from the Framingham Heart Study did not show expected cross-sectional
      associations of weight, body fat, and lean mass. The strongest associations were
      between IGF-I and nutritional indicators. These results suggest caution may be
      warranted with regard to use of IGF-I as an indicator of growth hormone.

PMID- 9033511
TI  - Financial performance among adult day centers: results of a national
      demonstration program.
AB  - OBJECTIVES: This paper describes the financial performance (defined as percent of
      total expenses covered by net operating revenue) of 16 adult day centers
      participating in a national demonstration program on day services for people with
      dementia, including examination of possible predictors of financial performance.
      METHODS: Participating sites submitted quarterly financial and utilization
      reports to the National Program Office. Descriptive statistics summarize the
      factors believed to influence financial performance. RESULTS: Sites averaged
      meeting 35% of expenses from self-pay and 29% from government (mainly Medicaid)
      revenue, totaling 64% of all (cash plus in-kind) expenses met by operating
      revenue. Examination of center characteristics suggests that factors related to
      meeting consumer needs, such as being open a full day (i.e., 7:30 am to 6:00 pm)
      rather than shorter hours, and providing transportation, may be related to
      improved utilization and, thus, improved financial performance. Higher fees were
      not related to lower enrollment, census, or revenue. CONCLUSIONS: Adult day
      centers are able to achieve financial viability through a combination of
      operating (i.e., fee-for-service) and non-operating revenue. Operating revenue is
      enhanced by placing emphasis on consumer responsiveness, such as being open a
      full day. Because higher fees were not related to lower utilization, centers
      should set fees to reflect actual costs. The figure of 64% of expenses met by
      operating revenue is conservative inasmuch as sites included in-kind revenue as
      expenses in their budgeting calculations, and percent of cash expenses met by
      operating revenue would be higher (approximately 75% for this group of centers).

PMID- 9033510
TI  - Bone mineral density and aortic calcification: the Study of Osteoporotic
      Fractures.
AB  - OBJECTIVE: To investigate the relationship between bone mineral density (in the
      axial and appendicular skeleton) and calcification of the aorta. DESIGN: Cross
      sectional study. SETTING: Community-based study. PARTICIPANTS: A total of 2051
      women aged 65 years and older enrolled in the Study of Osteoporotic Fractures.
      MEASUREMENTS: Bone mineral density (BMD) at the hip, spine, calcaneus, proximal
      and distal radius; calcification of the aorta (AC); demographic and lifestyle
      variables; dietary history; functional status; blood pressure; anthropomorphic
      measures. RESULTS: The prevalence of AC increased with age, ranging from 60% at
      ages 65 to 69 years to 96% at 85 years and older. BMD in women with calcified
      arterial plaques was lower (P < .001) when compared with those with no plaques,
      at all sites measured except the lumbar spine. After adjustment for age, BMD at
      the hip, spine and calcaneus was not associated with the presence of plaques;
      only a weak association between BMD and AC remained at the distal and proximal
      radius. The independent correlates of AC were age, smoking status, systolic blood
      pressure, coffee drinking, central obesity and a history of diabetes or stroke;
      current estrogen use was protective. CONCLUSIONS: The results of this study
      indicate that osteopenia and the deposition of calcific plaques in the wall of
      the aorta are independent processes that occur as women age. They are probably
      not causally linked.

PMID- 9033512
TI  - Cardiopulmonary resuscitation policies in long-term care facilities.
AB  - OBJECTIVES: To describe CPR policies and the procedures for discussing CPR
      policies of Wisconsin long-term care facilities. DESIGN: Mail survey and
      telephone interview. MEASUREMENTS: Information about CPR policy, how policy is
      disclosed to residents and by whom, emergency medical technician team (EMT)
      response time, and number of CPR attempts during 1993. RESULTS: The 1994 survey
      response rate was 85% (346/ 404 facilities). Four percent of responding
      facilities maintain a policy of never initiating CPR. Another 23% never initiate
      CPR but would call an EMT. Lack of efficacy was the usual basis for policies
      never initiating CPR. About 15% of facilities would initiate CPR only on
      residents who had previously indicated a preference. On individuals who had not
      made an advanced directive decision, 57% of facilities would initiate CPR in the
      event of an arrest. Almost 30% of facilities offering CPR would initiate CPR on
      unwitnessed arrests. Approximately 51% of all facilities assigned a social worker
      alone to discuss CPR policy and preference, whereas 12.5% assigned a physician
      alone or as part of a team. During 1993, an estimated 118 attempts at CPR were
      reported for 172 facilities with a total of 19,596 licensed beds, for a frequency
      of one CPR attempt per 166 beds per year. CONCLUSIONS: Poor efficacy in this
      population was the main reason given for policies of never initiating CPR.
      Specific factors relating to CPR efficacy, such as EMT response time and ease of
      maintaining trained staff, were not major influences. Almost 30% of facilities
      offering CPR would perform it in unwitnessed situations, despite unlikely
      success. Many decisions about CPR may not be fully informed as nurses and
      physicians are not often assigned to discuss advance directives with residents or
      surrogates. Utilization of CPR in nursing homes offering resuscitation is low.

PMID- 9033513
TI  - Over-the-counter medication use in an older rural community: the MoVIES Project.
AB  - OBJECTIVE: To examine the self-reported use of over-the-counter (OTC) medications
      and the factors associated with OTC use in a rural older population. DESIGN: A
      cross-sectional study of an age-stratified random community sample. SETTING: The
      mid-Monongahela Valley, a rural area of Southwestern Pennsylvania. PARTICIPANTS:
      A total of 1059 older individuals with a mean age of 74.5 (+/- 5.5) years, 96.9%
      of whom were white and 57.3% of whom were women. MEASUREMENTS: Self-reported over
      the-counter drug use and demographic information, and information about
      prescription drug use and recent use of health services. RESULTS: The majority
      (87.0%) of the sample were taking at least one OTC medication; 5.7% reported
      taking five or more OTCs. Women took significantly more OTCs than did men (P <
      .001). Individuals with more education took significantly more OTCs than those
      who had less (P = .018). The OTC category used most commonly was analgesics
      (66.3% overall), followed by vitamin and mineral supplements (38.1%), antacids
      (27.9%), and laxatives (9.7%). The use of analgesics decreased significantly (P =
      .018) with increasing age, whereas the use of laxatives increased significantly
      (P < .001). Women were more likely than men to be using each of these four major
      OTC groups. Unlike the associations with prescription drug use we reported
      previously in the same population, there were no significant associations for
      overall OTC use with age or with the use of health services. However, although
      vitamin use (as an example of an OTC drug taken for "preventive" purposes) was
      not associated with health services use, the use of laxatives (as an example of a
      "curative" OTC) was significantly associated (P < or = .002) with a greater
      number of physician visits, emergency room visits, hospitalizations during the
      past 6 months, home health care service utilization, and number of prescription
      medications. CONCLUSIONS: A substantial proportion of our older sample reported
      using a variety of over-the-counter drugs. Analgesics and vitamin/mineral
      supplements were the most frequently used categories. Women and those with more
      education were taking more OTC drugs. OTC use was not related to age, but the use
      of analgesics decreased with age while laxative use increased with age. Unlike
      prescription drug use, overall OTC drug use was not associated with health
      services utilization.

PMID- 9033514
TI  - Health status gender differences of newly admitted black nursing home residents.
AB  - OBJECTIVES: To investigate gender differences in health status of newly admitted
      black nursing home residents on the day following admission. DESIGN: Descriptive
      and comparative cross-sectional study of black residents drawn from a larger
      prospective longitudinal study on health and functional status of new nursing
      home residents interviewed on the first full day after admission. SETTING: Eight
      southern nursing homes: three not-for-profit, three for-profit, one county
      government-operated, and one federal government-operated. Homes ranged in size
      from 110 to 575 beds and were licensed for skilled and intermediate care.
      PARTICIPANTS: Black nursing home residents (N = 224) aged 60 years and older as
      admitted sequentially to nursing homes. MEASUREMENTS: Health status was assessed
      by the Short Portable Mental Status Questionnaire, as a measure of mental status,
      and the Scaled Outcome Criteria, as a measure of ability to perform activities of
      daily living (ADLs). Morbidity was assessed by the number of medical diagnoses,
      number of prescribed medications, and the medical diagnoses of hip fracture,
      dementia, and cancer. Resident classification data assessed the source of entry
      to the nursing home, payer source, and level of care required. Demographic data
      assessed included age, education, marital status, and number of living children.
      RESULTS: Both black men (n = 126) and women (n = 98) newly admitted to the
      nursing home had health and social deficits. Moreover, women, although not
      significantly different from men in average age, were more impaired in six of
      eight ADLs, including grooming, dressing, feeding, ambulating, transferring, and
      defecating. Women were also less likely to be married. No gender differences were
      found for five other health status variables, four other demographic variables,
      five resident classification variables, or five measures of morbidity.
      CONCLUSION: These data on southern black nursing home residents provide evidence
      that among older black nursing home residents, women have greater care needs than
      men. Findings illustrate the need to consider gender in planning nursing home
      care of black older residents, black women may be at greater risk for health
      status alterations and require more frequent health status monitoring and
      intervention.

PMID- 9033515
TI  - The prognostic significance of delirium in older hospital patients.
AB  - OBJECTIVES: To determine whether delirium is an independent predictor of adverse
      outcomes of hospitalization in older patients. DESIGN: Cohort study. PATIENTS: A
      total of 225 people admitted as an emergency to an acute geriatric unit in a
      university teaching hospital. METHODS: Subjects were screened for delirium,
      defined by Diagnostic and Statistical Manual, 3rd Edition criteria, every 48
      hours. Outcome measures included mortality, duration of hospital stay, hospital
      acquired complications, and institutional placement. The influence of delirium on
      these outcomes was calculated after adjusting for age, illness severity on
      admission, burden of comorbidity, prior cognitive impairment, and level of
      disability. RESULTS: Delirium was present on admission in 41 patients (18%) and
      developed after admission in a further 53 patients (24%). Patients with delirium
      were more likely than non-delirious patients to have chronic cognitive
      impairment, severe acute illness, multiple comorbid conditions, and functional
      disability. Nevertheless, in multivariate analyses adjusting for these factors,
      delirium was independently associated with prolonged hospital stay, functional
      decline during hospitalization, increased risk of developing a hospital-acquired
      complication, and with increased admission to long-term care. CONCLUSION:
      Delirium is an independent predictor of adverse outcomes in older hospital
      patients.

PMID- 9033516
TI  - The prevalence of potentially remediable urinary incontinence in frail older
      people: a study using the Minimum Data Set.
AB  - OBJECTIVES: To use the Minimum Data Set (MDS) to describe the frequency and
      correlates of potentially treatable causes of urinary incontinence among a
      representative sample of American nursing home residents. To describe current
      management practices of urinary incontinence in the same population. DESIGN:
      Cross-sectional study using the dataset that was part of the Health Care
      Financing Administration (HCFA) evaluation of the MDS. SETTING: 270 Medicaid
      certified nursing homes in 10 states. PARTICIPANTS: A total of 2014 nursing home
      residents 60 years or older (mean = 84.3 +/- 8.7), 75.5% women, 81.9% white, who
      lived in a nursing home during the fall of 1990 were randomly selected to sample
      a fixed number of residents for each facility based on facility size.
      MEASUREMENTS: Incontinence was defined as the presence of at least two episodes
      of urinary leakage per week in the previous 2 weeks. Management techniques
      (toileting, pads/briefs, catheters) were those listed in the MDS. Potentially
      remediable causes of urinary incontinence available in the MDS were: medications
      (antipsychotics, antidepressants, and antianxiety/hypnotics); congestive heart
      failure; diabetes mellitus; pedal edema; delirium; depression; and impairments in
      activities of daily living (ADLs) (transferring, locomotion, dressing, toileting;
      bedrails; trunk restraints; and chair restraints). RESULTS: Forty-nine percent of
      residents were incontinent. Of these, 84.0% were managed by pads/briefs, 38.7% by
      scheduled toileting, 3.5% by indwelling catheter, and 1.2% by external catheter.
      Of the potentially reversible causes, bivariate analysis revealed associations (P
      < .1) with use of antidepressants, antipsychotics, and antianxiety/hypnotics;
      delirium; bedrails; trunk restraints; chair restraints; and ADL impairment.
      Dementia was also associated with incontinence (P < .1). Multivariate analysis
      revealed that urinary incontinence was independently associated with impairment
      in ADLs (OR = 4.2; CI = 3.2,5.6), dementia (OR = 2.3;CI = 1.8,3.0), restraints
      trunk (OR = 1.7; CI = 1.5,2.0), chair (OR = 1.4; CI = 1.2,1.6), bedrails (OR =
      1.3; CI = 1.1,1.5), and use of antianxiety/hypnotic medications (OR = .7;CI =
      .5,1.0) (all P < .04). CONCLUSIONS: Current management practices for urinary
      incontinence are inconsistent with advocated guidelines. These data also confirm
      the association between incontinence and several potentially remediable
      conditions and suggest that, even in the nursing home setting, urinary
      incontinence may respond to efforts to improve conditions not directly related to
      bladder function. This study underscores the need to examine the impact on
      urinary incontinence of strategies to address such conditions.

PMID- 9033517
TI  - Recruitment in the Trial of Nonpharmacologic Intervention in the Elderly (TONE).
AB  - OBJECTIVE: To compare the effectiveness of different approaches to participant
      enrollment in a behavior modification trial. DESIGN: Concurrent, prospective
      evaluation performed in context of recruitment for a randomized, controlled
      trial. SETTING: Four study centers located in Baltimore, Maryland, Memphis,
      Tennessee New Brunswick, New Jersey, and Winston-Salem, North Carolina.
      PARTICIPANTS: Men and women aged 60 to 80 years who were being treated with a
      prescription medication for control of hypertension. MAIN OUTCOME MEASURES: Visit
      counts and percent yields were assessed at each stage of the screening and
      randomization process. Logistic regression was used to contrast the randomization
      yields for different recruitment strategies and to explore the impact of
      sociodemographic characteristics and geographic location on recruitment yields.
      RESULTS: The overall randomization yields from a prescreen contact and a first
      screening visit to enrollment in the trial were 11% and 31%, respectively.
      Randomization yields varied significantly by participant age, education, and
      marital status. CONCLUSIONS: Our results demonstrate the feasibility of
      recruitment for trials of nonpharmacologic interventions in older people and
      suggest that mass mailing and mass media advertising campaigns provide an
      effective means of enrolling in such studies participants with a broad range of
      personal characteristics.

PMID- 9033518
TI  - Sleep disturbances in Parkinson's disease patients and spouses.
AB  - OBJECTIVES: The prevalence of self-rated sleep disturbance in patients with
      Parkinson's disease (PD) and their spouses was compared with healthy controls,
      and the association of sleep disturbance with demographic, psychological, and
      disease variables was assessed. DESIGN: The sleep ratings from three groups, PD
      patients, their spouses, and healthy controls, were compared using analyses of
      variance. Stepwise regressions were used to predict sleep disturbance for each
      group and gender. SETTING: Participants completed questionnaires as part of a
      nationwide survey in Germany. PARTICIPANTS: Participants included 153 PD-spouse
      pairs and a group of 103 healthy controls. MEASUREMENTS: Zung Self-Rating
      Depression Scale and self-ratings of sleep disturbance, stress level, and disease
      symptoms (for PD patients). RESULTS: Sleep disturbances were significantly higher
      in women than in men in all groups. For PD patients, sleep disturbance occurred
      frequently in 25% of male and 41% of female participants and was best predicted
      by the patient's depression rating. For spouses, frequent sleep disturbance was
      reported by 27% of male and 48% of females and was likewise predicted by the
      spouse's own rating of depression. A second, relatively less common type of sleep
      disturbance was also reported by spouses. This disturbance was associated with
      waking during the night to help the patient and was best predicted by patient
      factors. CONCLUSION: Improvement of sleep quality of caregivers may be an
      important component of treatment to reduce distress caused by PD.

PMID- 9033519
TI  - A 90-year-old-woman with acute renal failure revealing an antiphospholipid
      syndrome.

PMID- 9033520
TI  - Driving cessation and increased depressive symptoms: prospective evidence from
      the New Haven EPESE. Established Populations for Epidemiologic Studies of the
      Elderly.
AB  - OBJECTIVES: The purpose of this study was to determine the association between
      driving cessation and depressive symptoms among older drivers. Previous efforts
      in this area have focused on the factors associated with cessation, not the
      consequences of having stopped. DESIGN: Cohort study. SETTING: Urban community.
      PARTICIPANTS: A driving survey was administered in 1989 to surviving
      noninstitutionalized members of the New Haven Established Populations for
      Epidemiologic Studies of the Elderly (EPESE) cohort. Of 1316 respondents, 502
      were active drivers as of 1988, 92 had stopped driving between 1982 and 1987, and
      the remainder had either never driven or had stopped before 1982. MEASUREMENTS:
      Information about independent and dependent variables other than driving status
      came from the in person EPESE interviews in 1982, 1985, and 1988, except for
      medical conditions, which were updated yearly. Depressive symptoms were assessed
      by the Centers for Epidemiologic Studies-Depression (CES-D) scale. Analyses
      focused on the changes in depressive symptoms before and after driving cessation.
      Repeated measures multivariable analysis accounted for the effect of cessation on
      the outcome adjusting for the potential confounding due to sociodemographic and
      health-related factors. RESULTS: Individuals who stopped driving exhibited
      substantial increases in depressive symptoms during the 6-year interval. Driving
      cessation was among the strongest predictors of increased depressive symptoms
      (Coefficient 2.464, SE 0.758, P = .001) even when adjusting for sociodemographic
      and health-related factors. CONCLUSIONS: Driving cessation was associated with an
      increase in depressive symptoms even when accounting for sociodemographic and
      health-related factors. These consequences need to be taken into account when
      advising older drivers and when developing alternative transportation strategies.

PMID- 9033521
TI  - Predictors of antipsychotic withdrawal or dose reduction in a randomized
      controlled trial of provider education.
AB  - OBJECTIVES: To evaluate the effects of an educational program to reduce
      antipsychotic use in nursing homes that had high use rates post-OBRA-87 and to
      identify factors that predicted antipsychotic withdrawal or 50% or greater dose
      reduction. DESIGN/SETTING: A randomized controlled trial (RCT) of the educational
      program (nursing home the unit of randomization and analysis) was conducted in 12
      Tennessee nursing homes (6 education/6 control). Cohort analysis in baseline
      antipsychotic users identified factors predicting withdrawal or dose reduction.
      SUBJECTS: The RCT analysis included 1152 patients in the homes at baseline and 6
      months. The cohort analysis included 133 baseline antipsychotic users in the five
      education homes able to implement the recommendations of the educational program.
      OUTCOME MEASURES: Change in days of antipsychotic use per 100 days of nursing
      home residence, withdrawal from antipsychotics, reduction in antipsychotic dose
      by 50% or more. RESULTS: Following the educational intervention, use of
      antipsychotics in the six education homes decreased from 25.3 days per 100 at
      baseline to 19.7 days per 100 by month 6, a 23% reduction relative to control
      homes (P = .014). In the withdrawal analysis, 44 (33%) of 133 baseline
      antipsychotic users were withdrawn. Factors at baseline predicting successful
      withdrawal were low antipsychotic dose, no use of benzodiazepines or
      antidepressants, and behavioral symptoms score below the median. However,
      although an additional 22 patients had dose reductions > or = 50%, none of the
      predictors of withdrawal were associated with dose reductions. CONCLUSIONS:
      Focused provider education programs may facilitate antipsychotic reduction above
      and beyond that attributable to regulatory changes. Patients who are poor
      candidates for total antipsychotic withdrawal may tolerate substantial dose
      reductions, which should reduce their risk of adverse antipsychotic effects.

PMID- 9033522
TI  - The benefits of in-home pharmacy evaluation for older persons.
AB  - OBJECTIVE: To assess the potential benefit of a pharmacist performing in-home
      medication evaluations on frail older people. DESIGN: Prospective analysis with
      pre-post comparison. SETTING: A hospital-based home care program at the Sepulveda
      Veterans Affairs Medical Center. PARTICIPANTS: Male veterans in a home care
      program who live within 15 miles of the medical center and take three or more
      prescription medications (N = 20, mean age: 75.1 years). MEASURES: Prescribed
      medications were documented from the medical records and compared with regimens
      actually being followed in the home. In addition, the home was inspected,
      patients were educated, and recommendations were made to the prescribing
      physicians when necessary. RESULTS: At first visit, patients had a mean of 6.0
      prescribed daily medications but were only taking 4.7 of these regularly. Also
      noted were many potentially unnecessary medications (70% of subjects) and
      multiple problems with the medication regimen (e.g., incorrect drug frequency or
      dosage, expired medications, medication omission). Follow-up visit revealed a
      significant decrease in medication discrepancies and problems (P < or = .05).
      CONCLUSION: An in-home pharmacy assessment reveals many problems with drug
      administration not otherwise detected easily. These assessments can lead to
      potentially useful interventions that can improve medication regimens and
      compliance. Determination of long-term effects must await controlled trials.

PMID- 9033523
TI  - Urinary and fecal incontinence in a community-residing older population in Japan.
AB  - OBJECTIVE: To estimate the prevalence and risk factors of urinary and fecal
      incontinence among a community-residing older population in Japan. DESIGN:
      Population-based cross-sectional study. SUBJECTS: A randomly selected sample of
      1473 people aged 65 years and older living in the City of Settsu, Osaka, in 1992.
      MEASURES: Data collected via in-home visits were used to estimate the prevalence
      of urinary and fecal incontinence and to provide information regarding potential
      risk factors of urinary and fecal incontinence. RESULTS: Data were obtained from
      1405 older adults, a response rate of 95.4%. The prevalence of any degree of
      urinary incontinence was 98/1000 in both sexes, and 87/ 1000 men and 66/1000
      women admitted to some degree of fecal incontinence. Daily, 34/1000 and 20/1000
      of the population were incontinent of urine and feces, respectively. There was an
      increasing prevalence of urinary and fecal incontinence with age in both sexes,
      but the expected greater prevalence in women was not found. By univariate
      analyses, age older than 75 years, poor general health as measured by Activities
      of Daily Living, stroke, dementia, no participation in social activities, and
      lack of life worth living (Ikigai) were associated significantly with both
      urinary and fecal incontinence. In the multivariate analyses using logistic
      regression, age older than 75 years, poor general health, and stroke were
      independent risk factors for any type of incontinence. Diabetes was an
      independent risk factor for isolated fecal incontinence, and dementia and no
      participation in social activities were independent risk factors for double
      incontinence. CONCLUSIONS: Incontinence of urine and feces is a prevalent
      condition among very old people living in the community in Japan and is
      associated highly with health and psychosocial conditions.

PMID- 9033524
TI  - Age-related changes in facial skin contours and rheology.
AB  - OBJECTIVES: To evaluate the age effect on both the mechanical properties and
      wrinkling of facial skin. This topic has not previously been addressed in the
      literature. DESIGN: A total of 180 white women aged 18 to 67 years participated
      in the study. Each of the 5 decades of age was represented by 30 subjects, with
      the exception of menopausal women aged 48 to 57 years who were allocated to two
      groups of 30 according to the use or non-use of hormone replacement therapy
      (HRT). SETTING: A University medical center, Belgian SSTC Research Unit 5596.
      MEASUREMENTS: Mechanical properties of the skin were measured on the face using a
      computerized suction device. Skin contours were assessed using optical
      profilometry and computerized image analysis. RESULTS: Skin aging of the face is
      characterized by a progressive increase in extensibility associated with a
      decreased elasticity. The loss of tonicity is accompanied by a progressive
      deepening of facial creases. HRT appears to limit the age-related rheological
      changes without showing a preventive effect on wrinkling of facial skin.
      CONCLUSION: Aging of facial skin resembles, in some ways, the features previously
      reported on sun-protected areas of the forearms. HRT has a beneficial effect that
      may slow the overall process of aging without, however, limiting the number and
      depth of wrinkles.

PMID- 9033525
TI  - Program of All-inclusive Care for the Elderly (PACE): an innovative model of
      integrated geriatric care and financing.
AB  - OBJECTIVES: The Program of All-inclusive Care for the Elderly (PACE) is a long
      term care delivery and financing innovation. A major goal of PACE is prevention
      of unnecessary use of hospital and nursing home care. SETTING: PACE serves
      enrollees in day centers and clinics, their homes, hospitals and nursing homes.
      Beginning at On Lok in San Francisco, the PACE model has been successfully
      replicated across the country. In 1995, PACE was fully operational in 11 cities
      in nine states. PARTICIPANTS: To enroll in PACE, a person must be 55 years of age
      or older, be certified by the state as eligible for care in a nursing home and
      live in the program's defined geographical catchment area. PACE participants are
      ethnically diverse. In 1995, the average PACE enrollee was 80.0 years old and had
      an average of 7.8 medical conditions and 2.7 dependencies in Activities of Daily
      Living. A significant number have bladder incontinence (55%). Many enrollees
      (39%) live alone in the community, and 14% have no means of informal support.
      INTERVENTION: Medicare and Medicaid waivers allow delivery of services beyond the
      usual Medicare and Medicaid benefits. The PACE service delivery system is
      comprehensive, uses an interdisciplinary team for care management, and integrates
      primary and specialty medical care. PACE receives monthly capitation payments
      from Medicare and Medicaid. Patients ineligible for Medicaid pay privately.
      RESULTS: Outcomes of PACE programs have been positive. There has been steady
      census growth, good consumer satisfaction, reduction in use of institutional
      care, controlled utilization of medical services, and cost savings to public and
      private payers of care, including Medicare and Medicaid. However, starting up a
      PACE program requires substantial time and capital, and the model has not yet
      attracted large numbers of older middle income adults. CONCLUSION: The growing
      number of older people in the United States challenges healthcare providers and
      policy makers alike to provide high quality care in an environment of shrinking
      resources. The PACE model's comprehensiveness of health and social services, its
      cost-effective coordinated system of care delivery, and its method of integrated
      financing have wide applicability and appeal.

PMID- 9033526
TI  - Parkinson's disease.

PMID- 9033527
TI  - The Cochrane Field in Health Care of Older People: geriatric medicine's role in
      the collaboration.

PMID- 9033528
TI  - PACE: a continuing evolving success.

PMID- 9033529
TI  - From Jezebel to a dead man walking: attempting resuscitation in long-term care.

PMID- 9033530
TI  - Outcomes of delirium: can systems of care make a difference?

PMID- 9033531
TI  - Duplicate publication of data.

PMID- 9033532
TI  - Who are the older patients failing to recover mobility after rehabilitation?

PMID- 9033533
TI  - Psychotic symptoms in Parkinson's disease.

PMID- 9033534
TI  - To use physical restraints or not.

PMID- 9033535
TI  - Barium aspiration in a heptagenarian.

PMID- 9033536
TI  - A spinal cord tumor masquerading as deconditioning.

PMID- 9033537
TI  - Elongation of life expectancy may accompany shift of medical cost to older
      adults.

PMID- 9033538
TI  - Drug use among urban older adults in China.

PMID- 9033539
TI  - Treatment of Pemphigus senilis with tetracycline plus nicotinamide: long term
      follow-up.

PMID- 9033540
TI  - The Mayos' appreciation for books.

PMID- 9033541
TI  - Intracoronary stent implantation in native coronary arteries and saphenous vein
      grafts: a consecutive experience with six types of stents without prolonged
      anticoagulation.
AB  - OBJECTIVE: To analyze the results of implantation of six different intracoronary
      stents without the use of prolonged anticoagulation. MATERIAL AND METHODS:
      Between Mar. 30, 1993, and Jun. 30, 1995, 889 patients with 1,194 coronary or
      vein graft lesions underwent implantation of one of six types of stents-Palmaz
      Schatz, Gianturco-Roubin, Wiktor, Micro, Cordis, or Wallstent. The patients were
      classified into seven groups on the basis of the type of stent that was
      implanted, including one group with combined use of two or more types of stents.
      Among the 851 patients with successful stent delivery and without major
      complications, 801 received only antiplatelet therapy, and 50 received a standard
      anticoagulation regimen. One-month clinical followup data were obtained in all
      patients, and clinical events were investigated. RESULTS: The mean number of
      stents was 1.8 per lesion and 2.4 per patient. Procedural success was achieved in
      93% of the lesions. The clinical success rate at 1 month was 90%. Intravascular
      ultrasound assessment was performed in 90% of the lesions. The final minimal
      luminal cross-sectional area of the stent increased from 6.8 to 7.8 mm2 after
      intravascular ultrasound-guided optimization. Within 1 month, 16 stent thrombosis
      events (1.9%) occurred. No significant differences were noted in stent thrombosis
      rates among the various stent cohorts. Multivariate logistic regression analysis
      revealed that the final stent minimal luminal diameter measured by intravascular
      ultrasonography was the only variable associated with stent thrombosis.
      CONCLUSION: This study showed that six different stents could possibly be
      inserted without subsequent anticoagulation if optimal stent expansion and total
      lesion coverage were achieved.

PMID- 9033542
TI  - Carcinoid tumors and sarcoidosis--does a link exist?
AB  - OBJECTIVE: To attempt to determine whether a relationship exists between
      carcinoid tumors and sarcoidosis. MATERIAL AND METHODS: We present a series of
      seven case reports and discuss hypotheses about possible disease associations.
      RESULTS: Certain malignant lesions have tended to occur in patients with
      sarcoidosis. Seven patients who were encountered at Mayo Clinic Rochester between
      1950 and 1994 had both sarcoidosis and carcinoid tumors. These patients ranged in
      age from 31 to 66 years, and three of the patients had a history of benign
      thyroid disorders. Malignant tumors have been thought to be related to
      sarcoidosis in one of two ways: (1) immunologic abnormalities in sarcoidosis may
      promote the development of neoplasms or (2) malignant disease may promote the
      onset of sarcoidosis either by causing local sarcoid reactions that progress or
      by directly initiating the manifestations of systemic sarcoidosis. Because the
      chronology of events differed in our seven cases, various mechanisms of action
      may have a role in the manifestations of these two disease entities. Our cases
      emphasize the importance of avoiding the diagnosis of disseminated malignant
      disease in patients with cancer and associated hilar and mediastinal
      lymphadenopathy without biopsy confirmation of metastatic disease. CONCLUSION:
      Application of the knowledge gained about the mechanisms of disease in
      sarcoidosis will perhaps facilitate identification of the pathogenesis of
      carcinoid tumors and other neuroendocrine tumors.

PMID- 9033543
TI  - Increased eosinophil granule proteins in gut lavage fluid from patients with
      inflammatory bowel disease.
AB  - OBJECTIVE: To explore the potential role of eosinophils in the pathogenesis of
      inflammatory bowel disease (IBD). DESIGN: We measured the concentrations of
      eosinophil granule proteins-namely, major basic protein, eosinophil peroxidase,
      eosinophil cationic protein, and eosinophil-derived neurotoxin-in gut lavage
      fluid. MATERIAL AND METHODS: Ten healthy persons and 17 patients with IBD (9 with
      Crohn's disease and 8 with ulcerative colitis) underwent gut lavage. Each study
      subject submitted an early specimen when lavage effluent became liquid and a late
      specimen when the output became clear. The concentrations of the granule proteins
      were measured by immunoassay. RESULTS: The median concentrations of eosinophil
      derived neurotoxin and eosinophil cationic protein were significantly higher in
      patients with IBD than in control subjects for both early and late lavage
      specimens. Excretion of eosinophil peroxidase was also significantly higher in
      patients with IBD than in the healthy control subjects, but only in the early
      specimens. No differences were noted in the concentrations of any of the proteins
      between patients with ulcerative colitis and those with Crohn's disease.
      CONCLUSION: Concentrations of eosinophil granule proteins were increased in whole
      gut lavage fluid from patients with IBD in comparison with healthy control
      subjects. These results encourage further studies of the role of eosinophils in
      the pathogenesis of IBD.

PMID- 9033544
TI  - Fetal renal growth evaluated by prenatal ultrasound examination.
AB  - OBJECTIVE: To determine reference ranges for normal fetal renal size in a
      population of pregnant patients at Mayo Clinic Rochester. DESIGN: Normal fetal
      kidneys were prospectively analyzed relative to gestational age and to fetal body
      weight. MATERIAL AND METHODS: In 100 pregnant women, prenatal ultrasound
      examinations were performed between 18 and 39 weeks of gestation. Fetal renal
      length and volume were determined by prenatal ultrasonography and compared with
      gestational age and estimated fetal body weight. Reference ranges as a function
      of gestational age were obtained for fetal body weight, renal length, renal
      volume, renal length/ body weight, and renal volume/body weight. Reference ranges
      as a function of body weight were determined for renal length and renal volume.
      Polynomial least-squares regression analysis was used to model each of the growth
      variables (Y) as a function of either gestational age or body weight (X).
      RESULTS: Graphic representation of these relationships are presented. These
      graphs include the 2.5, 5.0, 95.0, and 97.5 percentiles and the predicted value
      of Y from the regression equations. Fetal body weight, renal length, and renal
      volume increased throughout gestation, and the ratio between fetal renal volume
      and body weight remained constant. CONCLUSION: These data about normal fetal
      renal growth relative to gestational age and fetal body weight should help
      identify fetal abnormalities in renal size or growth patterns.

PMID- 9033545
TI  - Duodenal obstruction: diagnosis by gastroduodenal manometry.
AB  - Establishing the diagnosis of adenocarcinoma of the distal duodenum is often
      difficult based on findings on barium radiography and routine endoscopy of the
      upper gastrointestinal tract. A characteristic manometric pattern of
      simultaneous, prolonged contractions of the small intestine after a meal has been
      associated with mechanical obstruction of the small intestine. Herein we describe
      a 68-year-old woman who had a 4-month history of nausea, vomiting, and weight
      loss. Findings on endoscopy of the upper gastrointestinal tract and a barium
      contrast examination of the stomach, duodenum, and small bowel were interpreted
      as normal. A radionuclide scan suggested mildly delayed gastric emptying.
      Gastroduodenal manometry revealed high-amplitude, simultaneous contractions in
      the third and fourth portions of the duodenum but not in the jejunum, findings
      highly suggestive of a mechanical obstruction in the distal duodenum. At
      laparotomy, an obstructing adenocarcinoma of the duodenum proximal to the
      ligament of Treitz was resected. Subtle abnormalities were detected
      retrospectively on the barium contrast study of the small bowel. In patients with
      features suggestive of intestinal obstruction, gastroduodenal manometry may be
      helpful in distinguishing mechanical causes from pseudo-obstruction.

PMID- 9033546
TI  - Small-cell carcinoma of the lung manifesting as acute hepatic failure.
AB  - In this report, we describe four cases of small-cell carcinoma of the lung
      manifesting as acute hepatic failure. These cases were noteworthy for the
      presence of hepatomegaly and substantially increased serum lactate dehydrogenase
      and uric acid levels. The ratio of normalized serum lactate dehydrogenase to
      normalized serum alanine aminotransferase from the 4 cases reported herein (mean
      +/- SE, 3.63 +/- 1.10) was significantly greater than the ratio obtained from the
      12 cases of nonmalignant fulminant hepatic failure (mean +/- SE, 0.46 +/- 0.18; P
      < 0.001). Chest radiographs and abdominal imaging studies showed no neoplastic
      process in three of the four cases. Postmortem examinations disclosed extensive
      infiltration of the liver by metastatic small-cell carcinoma of the lung. A
      review of the literature revealed 13 additional similar cases. We conclude that
      metastatic small-cell carcinoma of the lung should be considered in cases of
      acute hepatic failure associated with hepatomegaly, substantially increased
      lactate dehydrogenase levels in comparison with alanine aminotransferase values,
      and increased uric acid levels even if imaging studies show no lesion. A liver
      biopsy done early during the hospital course is appropriate for diagnosis and for
      prevention of inappropriate transfer of the patient to a liver transplant center.

PMID- 9033547
TI  - Exercise-induced urticaria and anaphylaxis.
AB  - Exercise-induced urticaria and anaphylaxis have become increasingly recognized
      during the past 2 decades as more people participate in physical activities.
      These syndromes can be categorized as cholinergic urticaria or exercise-induced
      anaphylaxis based on the clinical manifestation. Newer subsets such as food
      dependent and familial exercise-induced anaphylaxis have also been recognized.
      Further studies are needed to characterize the variables involved in mast cell
      activation and mast cell mediator release in these syndromes. The management
      strategy for patients who have exercise-induced syndromes with skin
      manifestations only differs from the management for those with systemic symptoms.
      Currently, antihistamines, as a single agent or in combination with other agents,
      may be helpful prophylactically in both groups. Avoidance of precipitating
      factors, modification of exercise, and use of a self-injectable epinephrine kit
      are recommended for patients with anaphylaxis.

PMID- 9033548
TI  - Ernst Ruska--inventor of the electron microscope.

PMID- 9033549
TI  - Prophylactic antibiotics in cataract operations.
AB  - The rationale for prophylactic antibiotics in cataract operations must be
      continually reevaluated in light of cost-effectiveness and adverse reactions. The
      principles learned from wound infections associated with general surgical
      procedures should be applied to the limited knowledge about the rare event of
      endophthalmitis. Herein the literature on experimental and clinical wound
      infections in general surgical procedures is reviewed, with analysis of microbial
      flora, pathophysiology of wound infections, and pharmacokinetics of antibiotics.
      Experimental and clinical studies on prophylactic antibiotics to prevent
      endophthalmitis are reviewed, including information on topically applied
      antibiotics, chemical antisepsis, and administration of subconjunctival,
      intracameral, and systemic antibiotics. In addition, the benefits, limitations,
      and risks of the various types of prophylactic antibiotics are discussed. Because
      of the limited data on prophylactic antibiotics in cataract operations, providing
      dogmatic statements is difficult. General recommendations are offered based on
      the currently available literature, and a stratified approach is suggested based
      on wound construction and number of anterior segment maneuvers.

PMID- 9033551
TI  - 73-year-old man with gait disturbance and imbalance.

PMID- 9033550
TI  - Attitude and disposition: do they make a difference in cancer survival?
AB  - Psychosocial and spiritual factors influence a broad spectrum of medical and
      surgical disorders. The adverse effects of stress have been most clearly
      documented in cardiovascular disease. In cancer, unresolved questions include the
      following: Do emotional factors have a causal role in either initiating or
      promoting a malignant process, and can they possibly accelerate the dissemination
      of cancer? The literature, which consists of anecdotes, case-control methods, and
      randomized trials, is inconsistent and beset with major methodologic problems.
      Psychosocial interventions can be life enhancing in sharp contrast to the guilt
      ridden programs of some alternative practitioners. A social support system and an
      element of spirituality and religion seem to be the most consistent predictors of
      quality of life and possible survival among patients with advanced malignant
      disease.

PMID- 9033552
TI  - Posttransplantation physiologic features of the lung and obliterative
      bronchiolitis.
AB  - Obliterative bronchiolitis remains the major obstacle to long-term survival after
      lung transplantation. Herein we provide a brief review of the key literature as
      well as our own experience with this condition. Obliterative bronchiolitis has
      occurred in up to two-thirds of all lung transplant recipients. The
      characteristic physiologic changes include declines in (1) forced expiratory
      volume in 1 second, (2) forced vital capacity, and (3) diffusing capacity of the
      lungs for carbon monoxide. Lung biopsy in patients with obliterative
      bronchiolitis reveals occlusion of bronchioles in a patchy but extensive
      distribution. Mucous plugging and bronchiectasis may also be seen. Furthermore,
      intimal thickening of pulmonary vessels together with mild arteriosclerotic
      changes of the muscular and elastic pulmonary arterioles may be observed. To
      date, the main risk factor for the development of obliterative bronchiolitis is
      recurrent, severe, and persistent acute lung rejection. The recommended
      management is prevention because the established fibrotic condition may
      necessitate retransplantation.

PMID- 9033553
TI  - Medical management and complications in the lung transplant recipient.
AB  - Lung transplantation has evolved as a viable therapy for patients with end-stage
      lung disease. Improvements in surgical techniques, avoidance of rejection by
      effective strategies of immunosuppression, and other aspects of medical
      management allow successful lung transplantation, with 1-year survivorship of 70
      to 93%. In this review, we address the medical management of patients who have
      undergone lung transplantation. The immunosuppressive protocol used at Mayo
      Clinic Rochester is presented, along with a discussion of the mechanisms of
      action and potential complications associated with the various drugs used. The
      recognition and treatment of early graft dysfunction, infection, rejection,
      stenosis of the airway anastomosis, and posttransplantation lymphoproliferative
      disorder are also reviewed. Careful surveillance of patients after lung
      transplantation helps maintain graft function and facilitates identification,
      treatment, and potential avoidance of complications.

PMID- 9033554
TI  - Stents with high-pressure balloon inflations and intravascular ultrasonography-
      applicable in all patients?

PMID- 9033555
TI  - Childhood sexual abuse: concerns and consequences.

PMID- 9033556
TI  - Do anabolic-androgenic steroids enhance sporting performance?

PMID- 9033557
TI  - Guidelines: in search of certainty.

PMID- 9033558
TI  - Peanut allergy.

PMID- 9033559
TI  - Prevalence of childhood sexual abuse in a community sample of Australian women.
AB  - OBJECTIVE: To ascertain the prevalence of childhood sexual abuse (CSA) in a
      community sample of Australian women. DESIGN: Retrospective study, done in 1994,
      of cross-sectional data on the prevalence of CSA, collected as part of a larger
      two-stage case-control study of the possible relationship between CSA and alcohol
      abuse. Data were appropriately weighted to adjust for the different selection
      probabilities of cases and controls. PARTICIPANTS: 710 Women randomly selected
      from Australian federal electoral rolls. RESULTS: One hundred and forty-four
      women (20%) had experienced CSA. In 14 of these 144 women (10%), the abuse
      involved either vaginal or anal intercourse (i.e., 2% of the sample population
      experienced such abuse). The mean age at first episode of CSA was 10 years, and
      most (71%) of the women were aged under 12 years at the time. Perpetrators of the
      abuse were usually male (98%) and usually known to the child; 41% were relatives.
      The mean age of abusers was 34 years, with a median age difference of 24 years
      from that of the abused individual. Only 10% of CSA experiences were ever
      reported to the police, a doctor or a helping agency (e.g., community
      organisations, such as sexual assault services). CONCLUSION: The high rates of
      CSA (estimated to be 20% of all women) and low rates of reporting (10%) indicate
      the need for general practitioners and other health professionals to be aware
      that a history of such abuse may be common in women in the general population.

PMID- 9033560
TI  - Clinical practice guidelines in general practice: a national survey of recall,
      attitudes and impact.
AB  - OBJECTIVE: To determine Australian general practitioners' (GPs') views about and
      recall of clinical practice guidelines. DESIGN: Self-administered questionnaire
      survey. SUBJECTS: Randomly selected Australian GPs. RESULTS: 286 of 373 GPs
      returned questionnaires (77% response rate). GPs' recall of each of nine
      guidelines ranged from 52% to 94%; 49% considered that their practice had changed
      as a result of a guideline. While 92% of respondents agreed that guidelines were
      "good educational tools", 85% indicated that guidelines were "developed by
      experts who don't understand general practice". Factors most frequently
      identified as important in deciding whether to follow the guideline
      recommendations were whether the guideline was based on evidence and credible
      endorsement. CONCLUSIONS: Australian GPs have positive views about the purpose of
      clinical practice guidelines and an evidence-based approach to guidelines
      development. However, respondents rating of the perceived impact of available
      guidelines in everyday practice was low. The dissemination of specific guidelines
      is patchy and there is little evidence of systematic implementation.

PMID- 9033561
TI  - Visual impairment in nursing home residents: the Blue Mountains Eye Study.
AB  - OBJECTIVES: To assess the prevalence and causes of visual impairment, and the
      proportion of treatable eye conditions, among nursing home residents. DESIGN AND
      SETTING: The Blue Mountains Eye Study is a population-based survey of vision and
      common eye diseases in people aged 50 or older in two postcode areas west of
      Sydney. Nursing home examinations were conducted during 1993. PARTICIPANTS: Three
      representative nursing homes were selected from the nine in the study area. There
      were 128 residents aged 50 or older (64% females), representing 21% of all
      eligible nursing home residents in the two postcode areas. MAIN OUTCOME MEASURE:
      Blindness or visual impairment in one or both eyes. RESULTS: Eye examinations
      were refused by five nursing home residents, and dementia precluded eye
      examination in 34 (28%) of the remainder. We found significantly higher
      prevalences (fivefold increase) of bilateral (11%) and unilateral (21%) blindness
      in nursing home residents compared with local community residents (bilateral,
      0.5%; unilateral, 2%). In seven of the 10 blind nursing home residents, the
      blindness was potentially reversible (advanced cataract); late age-related
      macular degeneration (AMD) was the second most frequent cause of blindness,
      affecting one or both eyes of 12% of residents. Open-angle glaucoma affected 10%
      and advanced cataract 11%; a history of past cataract surgery was obtained in
      14%. CONCLUSIONS: These data confirm earlier reports of a substantial number of
      treatable eye diseases, particularly advanced cataract, in nursing home
      residents, and indicate a need for increased surveillance of these communities.
      The high rate of visual impairment and blindness, compared with similar age
      groups in the local community, suggests that visual disability may contribute to
      nursing home placement.

PMID- 9033562
TI  - Perinatal exposure to HIV in Australia, 1982-1994.
AB  - OBJECTIVE: To describe the pattern of perinatal exposure to HIV in Australia from
      1 January 1982 to 31 December 1994. DESIGN: National surveillance for perinatal
      exposure to HIV. PARTICIPANTS AND SETTING: Women with diagnosed HIV infection in
      Australia whose children were exposed to HIV perinatally. OUTCOME MEASURES:
      Number of reported cases of women with diagnosed HIV infection who have had
      perinatally HIV-exposed children. RESULTS: By 31 December 1994, 91 women
      diagnosed with HIV infection had had 111 perinatally exposed children. While the
      rate of perinatal exposure to HIV was highest in the Australian Capital Territory
      and New South Wales, the rate was substantially lower than the rate of diagnoses
      of HIV and AIDS in women of child-bearing age. Before 1989, only 15% (6/39) of
      women knew of their HIV infection before the birth of their first perinatally
      exposed child: by 1989-1994, this had increased to 64% (32/52; P < 0.0005).
      Overall, exposure to HIV was attributed to heterosexual contact only, injecting
      drug use or receipt of blood or tissue by 48%, 31% and 18% of women,
      respectively. Source of HIV exposure changed from a history of receipt of blood
      in 78% of women whose first exposed child was born in 1982-1985 to heterosexual
      contact only in 61% of women whose first exposed child was born in 1992-1994. 38
      children acquired HIV infection perinatally. The HIV transmission rate to
      children born to women diagnosed with HIV infection before delivery was 21.6%
      (11/51). CONCLUSIONS: Perinatal exposure to HIV in Australia remains rare. While
      the proportion of women diagnosed with HIV infection after delivery decreased, a
      substantial number continued to be diagnosed after delivery, precluding use of
      current interventions that can reduce the risk of perinatal transmission. It may
      be appropriate to review the application of HIV testing during pregnancy in
      Australia.

PMID- 9033563
TI  - Plasmodium vivax malaria acquired in far north Queensland.
AB  - In February 1996, vivax malaria was diagnosed in a man from a remote community in
      far north Queensland who had not visited a malarious area for the past 19 years.
      Microscopy and DNA studies of blood from other residents of the community did not
      identify a source of infection. It was suspected the infection was transmitted by
      mosquitoes from a neighbour who had been infected in Papua New Guinea, but whose
      blood was not available for DNA tests.

PMID- 9033564
TI  - The epidemic of post-traumatic stress disorder: a passing phase?

PMID- 9033565
TI  - Post-traumatic stress disorder: the importance of clinical objectivity and
      systematic research.

PMID- 9033566
TI  - The role of the general practitioner in the treatment of schizophrenia: general
      principles.
AB  - In light of the emphasis on community care for schizophrenia and the increasing
      role likely to be played by general practitioners, this paper describes some of
      the general principles involved in the treatment of this disorder and provides a
      set of practical guidelines to assist general practitioners.

PMID- 9033567
TI  - Changes to postgraduate medical training in the United Kingdom: implications for
      Australasian doctors.
AB  - Recent changes to postgraduate medical training and specialist registration in
      the United Kingdom will affect visiting Australasian doctors. Postgraduate
      training will be more structured and focused. However, from January 1997
      Australasian doctors are likely to find it more difficult to work in substantive
      (or honorary) specialist posts.

PMID- 9033568
TI  - Osteoarthritis.

PMID- 9033569
TI  - School bus-related deaths and injuries in New South Wales.

PMID- 9033570
TI  - School bus-related deaths and injuries in New South Wales.

PMID- 9033572
TI  - Glucose tolerance testing and gestational diabetes.

PMID- 9033573
TI  - Motor neurone disease and the life of motor neurones.

PMID- 9033574
TI  - Motor neurone disease and the life of motor neurones.

PMID- 9033575
TI  - Home chemotherapy for cancer patients: cost analysis and safety.

PMID- 9033576
TI  - Polyvalent vaccines and the National Immunisation Schedule.

PMID- 9033577
TI  - Ionising radiation in diagnosis: do the risks outweigh the benefits?

PMID- 9033578
TI  - Post-traumatic stress disorder: what's in a name?

PMID- 9033579
TI  - HIV and choosing to die.

PMID- 9033580
TI  - Fault lines in the HIV core?

PMID- 9033581
TI  - GAGA over the nucleosome.

PMID- 9033582
TI  - Penetrating insights into pore formation.

PMID- 9033583
TI  - Size is everything.

PMID- 9033584
TI  - Into the black of night.

PMID- 9033585
TI  - Crystal structure of a peptide nucleic acid (PNA) duplex at 1.7 A resolution.
AB  - The crystal structure of a PNA duplex reveals both a right- and a left-handed
      helix in the unit cell. The helices are wide (28A), large pitched (18bp) with the
      base pairs perpendicular to the helix axis, thereby demonstrating that PNA
      besides adapting to oligonucleotide partners also has a unique structure by
      itself.

PMID- 9033586
TI  - The RecA hexamer is a structural homologue of ring helicases.
AB  - The RecA protein forms a hexameric ring that is similar to the core of the F1
      ATPase. Several lines of evidence suggest that this hexamer may be a structural
      homologue of ring helicases.

PMID- 9033587
TI  - Crystal structure of human cathepsin K complexed with a potent inhibitor.

PMID- 9033588
TI  - Crystal structure of human osteoclast cathepsin K complex with E-64.

PMID- 9033589
TI  - Phosphorylation destabilizes alpha-helices.
AB  - Phosphorylation of threonine destabilizes the leucine zipper of a bZIP protein by
      4.6 kcal mol-1 dimer-1, which reduces DNA binding 100-fold. This decrease in
      stability reflects the low alpha-helix forming propensity of a phosphorylated
      threonine.

PMID- 9033590
TI  - Certain bZIP peptides bind DNA sequentially as monomers and dimerize on the DNA.

PMID- 9033591
TI  - Three-dimensional visualization of mRNA release from actively transcribing
      rotavirus particles.

PMID- 9033592
TI  - Picture story. Take away this ball and chain.

PMID- 9033593
TI  - The solution structure of a specific GAGA factor-DNA complex reveals a modular
      binding mode.
AB  - The structure of a complex between the DNA binding domain of the GAGA factor
      (GAGA-DBD) and an oligonucleotide containing its GAGAG consensus binding site has
      been determined by nuclear magnetic resonance spectroscopy. The GAGA-DBD
      comprises a single classical Cys2-His2 zinc finger core, and an N-terminal
      extension containing two highly basic regions, BR1 and BR2. The zinc finger core
      binds in the major groove and recognizes the first three GAG bases of the
      consensus in a manner similar to that seen in other classical zinc finger-DNA
      complexes. Unlike the latter, which require tandem zinc finger repeats with a
      minimum of two units for high affinity binding, the GAGA-DBD makes use of only a
      single finger complemented by BR1 and BR2. BR2 forms a helix that interacts in
      the major groove recognizing the last G of the consensus, while BR1 wraps around
      the DNA in the minor groove and recognizes the A in the fourth position of the
      consensus. The implications of the structure of the GAGA-DBD-DNA complex for
      chromatin remodelling are discussed.

PMID- 9033594
TI  - The ATP-dependent HslVU protease from Escherichia coli is a four-ring structure
      resembling the proteasome.
AB  - HslVU is a new two-component protease in Escherichia coli composed of the
      proteasome-related peptidase HslIV and the ATPase HsIU. We have used electron
      microscopy and image analysis to examine the structural organization of HslV and
      HslU homo-oligomers and the active HslVU enzyme. Electron micrographs of HslV
      reveal ring-shaped particles, and averaging of top views reveal six-fold
      rotational symmetry, in contrast to other beta-type proteasome subunits, which
      form rings with seven-fold symmetry. Side views of HslV show two rings stacked
      together, thus, HslV behaves as dodecamer. The ATPase HslU forms ring-shaped
      particles in the presence of ATP, AMP-PNP or ADP, suggesting that nucleotide
      binding, but not hydrolysis, is required for oligomerization. Subunit
      crosslinking, STEM mass estimation, and analysis of HslU top views indicate that
      HslU exists both as hexameric and heptameric rings. With AMP-PNP present, maximal
      proteolytic activity is observed with a molar ratio of HslU to HslV subunits of
      1:1, and negative staining electron microscopy shows that HslV and HsIU form
      cylindrical four-ring structures in which the HsIV dodecamer is flanked at each
      end by a HslU ring.

PMID- 9033595
TI  - The structure of the cytochrome p450BM-3 haem domain complexed with the fatty
      acid substrate, palmitoleic acid.
AB  - The substrate-bound structures of two cytochrome P450s, P450cam and P450eryF, are
      known. While these structures reveal important features that control substrate
      specificity, the problem of how conformational changes allow for substrate entry
      and product release remains unsolved. The structure of the haem domain of the
      bacterial fatty acid hydroxylase, P450BM-3, previously was solved in the
      substrate-free form. Unlike the substrate-bound P450cam and P450eryF structures,
      the substrate access channel is open in substrate-free P450BM-3. Here we present
      the X-ray structure of P450BM-3 at 2.7 A bound with a fatty acid substrate,
      palmitoleic acid. A comparison of the substrate-bound and -free forms reveals
      major conformational differences and provides the first detailed picture of
      substrate-induced conformational changes in a P450.

PMID- 9033596
TI  - The crystal structure of human rac1, a member of the rho-family complexed with a
      GTP analogue.
AB  - The crystal structure of human rac1, a member of the rho family of small G
      proteins, complexed with the non-hydrolysable GTP analogue, guanosine-5'-(beta
      gamma-imino)triphosphate (GMPPNP), has been determined by X-ray analysis at a
      resolution of 1.38 A. Comparison with the structure of H-ras indicates that rac1
      has an extra alpha-helical domain that is characteristic of the rho G proteins,
      and may be involved in the signalling pathway of this family.

PMID- 9033597
TI  - Crystal structure of human mitochondrial single-stranded DNA binding protein at
      2.4 A resolution.
AB  - We solved the crystal structure of the homotetrameric single-stranded DNA binding
      (SSB) protein from human mitochondria at a resolution of 2.4 A. The tetramer is
      formed by two dimers interacting head-to-head and shows D2 symmetry. Sequence
      related tetrameric SSB proteins occur in prokaryotes and eukaryotic mitochondria;
      this is the first report of an atomic resolution structure of this type of
      protein. Using biochemical data and analysis of sequence homologies, we were able
      to correlate the functional properties with structure. We propose that ssDNA
      wraps around the tetrameric HsmtSSB protein through electropositive channels
      guided by flexible loops.

PMID- 9033599
TI  - [Top-Forum: an interactive multimedia knowledge database to improve quality of
      care in pediatric oncology].
AB  - The treatment of pediatric cancer patients is characterised by complex and
      aggressive chemotherapy, difficult decision making, the numerous protocols
      available and the necessity of highly skilled caregivers. Quality of care is a
      major issue in all pediatric oncology units. We created an interactive multi
      media database available to each caregiver to permit him/her to have easy access
      to information and thus increase his/her knowledge and participate in increasing
      their group's know-how. The computer database is available to all on a free
      access basis in each ward. This is a novel approach to quality care, as it
      accords great importance to personal formation, allowing each caregiver to
      broaden his/her knowledge via easily obtained data which he/she can help enrich
      by permanent feedback. This database may become the backbone of department know
      how.

PMID- 9033598
TI  - [Role of amphetamines in cancerology : a review of the literature].
AB  - The review of the literature shows that amphetamines (methylphenidate,
      dextroamphetamine) have been rarely used in the past, but have been recently
      introduced in the palliative treatment in oncology. They have stimulating,
      antidepressive and perhaps coanalgesic effects. They can alleviate sleepiness
      related to opiates analgesics which are given in chronic pain. Amphetamines may
      also be a therapeutic option, alone or in association with antidepressant drugs,
      in the pharmacological management of mood disorders unresponsive to tricyclics or
      selective serotonin reuptake inhibitors. These treatments are well-tolerated and
      are rapidly active. This treatment may improve the quality of life and comfort in
      cancer patients.

PMID- 9033600
TI  - [Current trends in lung cancer mortality in France].
AB  - Lung cancer is the first cause of death from cancer in males in France. This
      cancer is responsible for 19,000 deaths in males and 3,000 deaths in females. We
      studied the geographical and temporal variations in lung cancer mortality in
      France. The average increase in mortality clearly decreased in males, changing
      from 2.4% between 1971 and 1985 to 0.7% between 1985 and 1992. In females, this
      tendency is reversed. Even though the rates were stable and very low before 1971,
      we have since observed a progressive increase which has intensified during the
      past years. Thus the average annual increase changed from 1.5% between 1971 and
      1985 to 3% between 1985 and 1992. The geographic comparisons between the two
      studied periods (1971-78 and 1987-92) showed important differences between males
      and females. The geographic disparities among males were stable between these two
      periods. The excess observed mortality rate was maintained in the north-east.
      Among females, few geographic variations were observed during the first period.
      The second period however, showed distinct excess mortality rates in urban areas
      and large conglomerations as compared to the rest of France. In summary, the
      increase in the mortality rates for lung cancer is more pronounced in females and
      seems to have diminished in males, particularly in urban areas. This tendency
      started in the 1980s.

PMID- 9033602
TI  - [Chemical stability of pirarubicin in its use for continuous infusion].
AB  - The aim of this study was to examine the chemical stability of pirarubicin in
      conditions close to ambulatory continuous infusions (infusor). The analyses were
      performed using an HPLC method in two infusion fluids (G5% and water), in
      different conditions of conservation (light and obscurity) and at different
      temperatures (+35 degrees C and +4 degrees C). The results demonstrated that
      light did not increase the chemical degradation of pirarubicin in doxorubicin
      which occurred more rapidly in G5% than in water. On the other hand, the
      temperature was a comparably major influence (> than 80% of deterioration in 7
      days). In conclusion, the use of pirarubicin in continuous infusion (5 days
      infusors) is currently impossible without leading to a fast and important outcome
      of doxorubicin, which present different therapeutic activity and different
      toxicity.

PMID- 9033601
TI  - [Changes of the cutaneous micro-relief in superficial radiation-induced fibrosis:
      a qualitative study].
AB  - Cutaneous radiation-induced fibrosis (RIF) is characterized by a skin retraction
      or atrophy, toughness to the palpation and often entails functional limitation.
      Its clinical evaluation remains poorly quantified. The aim of this study was to
      propose an analytical method to quantify RIF skin surface with the replica
      technique. In this preliminary study, we report the qualitative and quantitative
      evaluation of the cutaneous microrelief in 44 healthy controls and in four
      patients presenting a superficial RIF, 3 to 20 years after radiotherapy for
      cancer. The microrelief of these RIF presented an abnormal anisotropy with a
      parallel reorganization of cutaneous valleys in three cases out of four,
      suggesting a premature radiation-induced ageing of the skin. Each subject being
      his own control, the relative vertical amplitude of the skin microrelief was +/
      15% in control skin. Vertical amplitude was respectively increased by 84% in one
      inflammatory fibrosis (3 years after RT), decreased by 18% in one evolutive
      fibrosis (6 years after RT), decreased by 26% in one voluminous stabilized
      fibrosis (8 years after RT) and decreased by 53% in one atrophic fibrosis (20
      years after RT). The present study suggests that the variations of the
      microrelief parameters could reflect the RIF evolution. This technique requires a
      validation in a larger series of patients, including patients with
      telangiectasia.

PMID- 9033603
TI  - [Radiological features of thoracic localizations of lymphomas].
AB  - This retrospective work aims to analyse the incidence and the radiologic features
      of initial thoracic involvement of lymphomas, observed in 320 patients selected
      among 1,153 lymphomas (640 Hodgkin's diseases and 513 non-Hodgkin's lymphomas).
      Thoracic involvement was not observed in 833 (72%) patients with lymphoma. In
      Hodgkin's disease (HD) (n = 200) thoracic involvement was observed in 31%
      (200/640). The mediastinal lymph nodes were noted in 99.5% and predominated in
      the superior and mid mediastinum in 84.5%. Mediastino-thoracic ratio was superior
      to 0.33 in 33.5%. Unilateral paratracheal nodes were involved in 26% and the
      hilar groups in 39.5%. The lung involvement was present in 26.5%, such as nodules
      in 11% and alveolar infiltration in 6.5%. In the cases with lung involvement,
      there were concomitant mediastinal lymph nodes. Pleural and pericardial effusions
      were seen in 23.5% and 4%. Parietal involvement was noted in 1%. In non-Hodgkin's
      lymphomas (NHL) (n = 120) thoracic involvement was observed in 23% (120/513). The
      mediastinal lymph nodes were seen in 82.5%, located in superior and mid
      mediastinum in 60%. Mediastino-thoracic ratio was superior to 0.33 in 47%. Lymph
      nodes were unilateral paratracheal in 7.5% and hilar in 18%. The posterior
      mediastinal lymph nodes group was involved in 2%. Lung involvement was noted in
      24%, pleural effusion in 48%, pericardial effusion in 4% and parietal involvement
      in 2.5%. In the cases of thoracic involvement in HD, mediastinal lymph nodes
      involvement is constant, affecting commonly the anterior mediastinal,
      paratracheal and hilar groups. Involvement of the posterior mediastinum and
      paracardiac groups is more common in NHL. Thoracic computed tomography is helpful
      in the detection of the abnormalities misdiagnosed on the chest X-ray. Computed
      tomography is valuable in the initial stages of HD because it can modify the
      treatment in 15%.

PMID- 9033604
TI  - [Value of postoperative radiotherapy in malignant tumors of the upper urinary
      tract. Apropos of a series of 26 patients].
AB  - To evaluate the role of adjuvant radiation therapy in invasive transitional cell
      carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26
      patients who underwent radical surgery plus post-operative prophylactic
      irradiation for such a tumor. Between 1980 and October 1993, 18 men and eight
      women (mean age: 65 +/- 9 years) were treated for an invasive transitional cell
      carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15
      patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage
      C in 15 patients (58%). Tumor grade was 2 in ten patients, 3 in 15 and unknown in
      one. Nine patients had node involvement. All patients underwent surgery followed
      by radiation therapy to a total dose of 45 Gy to the tumor bed (23 patients)
      and/or regional nodes (18 patients). After a mean follow-up of 45 months, 13
      patients (50%) were alive and 11 were disease-free. Local tumor relapse, nodal
      recurrence, metastasis and second urothelial location were noted in one, four
      (15%), 14 (54%) and eight patients (30%) respectively. Overall 5-year survival
      and 5-year disease-free survival were 49% and 30% respectively. Overall 5-year
      survival rates were 60% for stage B and 19% for stage C disease (P = 0.07), 43%
      for node-negative versus 15% for node-positive cancer (P = 0.04) and 90% for
      grade 2 and 0% for grade 3 tumors (P < 0.01). In this study using a radio
      surgical approach, local control of disease and survival were similar to those
      reported previously in surgical series. Prophylactic post-operative radiation
      therapy is not recommended.

PMID- 9033605
TI  - [Bladder neoplasms and cyclophosphamide. Apropos pf 3 cases amd review of the
      literature].
AB  - We report three new cases of bladder cancer occurring in patients treated by
      cyclophosphamide (Endoxan): two patients had Waldenstrom disease and were treated
      during 7.5 and 7 years respectively (total received dose of 220 and 190 g
      respectively). The third patient was treated for autoimmune erythroblastopenia
      and the bladder cancer occurred 5 years after treatment by cyclophosphamide (39 g
      during 3.3 years). Bladder cancers after cyclophosphamide treatment are generally
      transitional cell carcinomas. They are observed after an oral treatment,
      generally given for more than one year. A cumulative dose of more than 20 g is
      the principal risk factor, with a median interval from treatment to tumor of 7
      years. No other risk factor has been identified (tobacco, age, sex, hemorrhagic
      cystitis). The relative risk of bladder cancer is estimated between 7 and 9, and
      seems proportional to the cumulative dose of cyclophosphamide. The first
      hypothesis to explain bladder cancer occurrence is a carcinogenic effect of one
      of the cyclophosphamide metabolites, acrolein, but the immunosuppressive effect
      of cyclophosphamide may play a role. The risk of secondary bladder cancer implies
      to limit the use of cyclophosphamide, particularly in non malignant disease, and
      to closely watch the patient especially by way of annual cystoscopy.

PMID- 9033606
TI  - [Malignant synovial "chondromatosis" or chondrosarcomatous transformation of
      synovial chondromatosis of the knee?].
AB  - A case of chondrosarcoma of the knee with clinical and histopathological features
      of malignant chondromatosis in a 40-year-old white man is reported. Malignant
      transformation of true chondromatosis is uncommon and has important implication
      of diagnosis and surgical treatment.

PMID- 9033607
TI  - [A case of degenerated diffuse biliary papillomatosis associated with cystic
      dilatation of the intrahepatic biliary ducts. Value of radiotherapy and review of
      the literature].

PMID- 9033609
TI  - [Hodgkin's disease in the very young child. Apropos of 11 cases].
AB  - Hodgkin's disease (HD) in children of 4 years of age or younger is seldom
      reported. It seems more frequent in developing countries. We report on 11 cases
      out of 115 cases of HD in patients of 15 years of age or younger observed between
      1980 and 1991. The youngest patient was 29 months old and the median age was 2
      years 11/12. The male/female ratio was 2.6. Mixed cellularity was found in six
      cases, lymphocytic predominance in two cases and nodular sclerosis in two cases.
      B symptoms were observed in four cases. Four patients had stage II, three stage
      III and four stage IV disease. Chemotherapy consisted of MOPP/ABVD in all cases.
      One patient received mantle field radiation therapy. Of ten evaluable patients,
      seven achieved complete remission, three patients were lost to follow-up in
      partial remission before achieving the treatment program. There were no relapses
      so far and no death attributable to toxicity. The follow-up ranges from 2 to 8
      years. These data indicate the high frequency of HD in very young patients and
      suggest that chemotherapy alone is very efficient in this subset of patients.

PMID- 9033608
TI  - [Malignant mesothelioma of the pleura following radiotherapy of Hodgkin disease].
AB  - Second neoplasms following chemotherapy and radiotherapy for Hodgkin's disease
      have been extensively described, including acute myeloblastic leukemia, non
      Hodgkin's lymphomas and various solid tumors. We report malignant pleural
      mesothelioma occurring 17 years after mantle radiotherapy and MOPP chemotherapy
      for Hodgkin's disease. According to Cahan's criteria, this mesothelioma may be
      considered as treatment-related. Fourteen similar cases have been previously
      published. Post-radiation mesothelioma might be characterised by limited stage at
      diagnosis and might be surgically removed at presentation.

PMID- 9033610
TI  - [Is therapeutics a specialty? Association Pedagogique Nationale des Enseignants
      de Therapeutique].

PMID- 9033611
TI  - [Tuberculosis. Current therapeutics].
AB  - Due to the constant decline in incidence up to the mid eighties, eradication of
      tuberculosis appeared to be an attainable objective in developed countries. Since
      then multiple factors (HIV epidemic, poor social conditions in certain unfavored
      areas, population migrations, urbanization) have led to an increased frequency,
      making an excellent knowledge of tuberculosis a priority for all physicians.
      Multi-resistant mycobacteria have also made their appearance leading to numerous
      clinical and experimental studies which provide new insights into the correct
      management of patients with tuberculosis. Despite these recent changes, the
      classical treatment for tuberculosis remains the same in most cases, allowing
      nearly-certain cure when applied correctly in patients infected with a
      susceptible bacteria, including those with HIV infection or extrapulmonary
      localizations. On the contrary, the spontaneous aggravation of multi-resistant
      tuberculosis, even in some cases being treated, emphasizes the need to test the
      strain's susceptibility to the antituberculous agents used. Certain new
      antibiotics, including fluoroquinolones, may play an important role in some
      cases. The contribution of surgery, isolation and strict compliance must also be
      emphasized. Resistant strains may also led to renewed indications for the
      Calmette-Guerin vaccine.

PMID- 9033612
TI  - [The treatment of Helicobacter pylori infection].
AB  - H. pylori causes inflammatory lesions of the stomach and duodenum. At the present
      time eradication is essentially recommended in case of gastric or duodenal ulcer.
      The choice of the appropriate drug depends on the characteristics of the H.
      pylori infection, the localization deep in the gastric mucosa, the physico
      chemical properties of the gastric medium, especially the acidity which
      deactivates antibiotics, slow bacterial growth and the germ's sensitivity to
      antibiotics. Anti-infectious treatment is now based on a three-drug regimen
      combining an antisecretory drug (proton pump inhibitor or H2 receptor antagonist)
      and two antibiotics: clarithromycin associated with amoxicillin or an imidazol
      derivative (metronidazol or tinidazol) or tetracycline. Two antibiotics
      (clarithromycin, amoxicillin) as well as three anti-secretory agents
      (lansoprazole, omeprazole, ranitidine) have been authorized in France for three
      drug regimens of 1 or 2 weeks leading to approximately 90% eradication. Special
      attention should be placed on the risk of resistance to antibiotics (macrolids
      and imidazol derivatives) and patient compliance required for successful
      eradication of H. pylori. Other therapeutic schemes are under assessment and a
      vaccine is being prepared. Eradication of H. pylori has totally changed the
      treatment of gastric and duodenal ulcers, eliminating the need for long-term
      treatment and avoiding complications.

PMID- 9033613
TI  - [Prophylaxis of infectious endocarditis].
AB  - Prophylaxis of infective endocarditis has been the subject of recommendations
      from most countries for several years. The basis of the recommendations is the
      administration of prophylactic antibiotics preceding a procedure at risk for
      patients with a known at risk cardiac disease. The antimicrobial agent is
      selected to be active against the main microorganisms causing bacteremia
      according to the type of at risk procedure. Furthermore, the choice and
      modalities of antibiotic prophylaxis are adapted to take into account a possible
      documented allergy to penicillin, the type of predisposing cardiac disease, the
      number of performed procedures and the requirement for general anesthesia. Future
      advances should concern the diffusion and application of these recommendations,
      and the appropriateness of these practices in terms of general cost benefit
      assessment.

PMID- 9033614
TI  - [Non-cancer uses of methotrexate].
AB  - Methotrexate, used for nearly 40 years as an antimetabolite for cancer therapy,
      also has indications in dermatology, rheumatology and pneumology. When given at
      low dosage, it has an antiinflammatory effect although the mechanism is not
      totally understood. Numerous therapeutic trials have been performed in chronic
      inflammatory diseases such as rheumatoid arthritis in the adult, juvenile
      polyarthritis and corticosteroid-dependent asthma. Methotrexate is effective in
      severe resistant forms of rheumatoid arthritis and is used either alone or in
      combination with other drugs as first intention therapy because of the good
      tolerance, patient compliance and ease of use. The beneficial effect in severe
      corticosteroid-dependent asthma remains to be demonstrated. It has also been used
      in severe forms of psoriasis and may be useful in other diseases with an
      autoimmune component. Other less common indications including Crohn's disease,
      ectopic pregnancy and pregnancy termination require confirmation. Tolerance and
      compliance are generally good, even for prolonged treatments and undesirable
      effects are almost always reversible at withdrawal.

PMID- 9033615
TI  - [Prevention of deep venous thrombosis in medical care].
AB  - Venous thromboembolism is a frequent and potentially severe ailment in medical
      patients; the clinical signs are unreliable and as early detection of the
      thrombosis process by non-invasive techniques is not available, prevention
      appears to be an alternative. Careful definition of the medical situations at
      risk from venous thromboembolism is necessary. Age, prior history of venous
      thromboembolism, and immobilization constitute high risk circumstances. Analysis
      of the published studies advocates prevention in three circumstances: myocardial
      infarction, stroke and intensive care. In other cases, further controlled
      studies, randomized versus placebo, are needed.

PMID- 9033616
TI  - [First intention treatment of arterial hypertension using a combination of two
      drugs].
AB  - The limited efficacy of single-drug regimens in the treatment of high blood
      pressure has led to an evaluation of combination regimens for first intention
      treatment. Two-drug regimens favor the hypotensive efficacy and reduce the
      frequency of certain side effects. Medications combining two drugs in a single
      formulation would allow use as first line treatment although marketing
      authorizations have not yet been obtained. In addition, current good clinical
      practice recommendations do not allow combination therapy in this situation. A
      complete assessment based on medical results and cost effectiveness will
      undoubtedly confirm the usefulness of two-drug therapies as first line treatment
      for moderate hypertension.

PMID- 9033617
TI  - [Treatment of viral hepatitis C].
AB  - Viral hepatitis C is a serious public health problem in France by the number of
      infected patients, the evolutive profile and by the lack of fully efficient
      therapeutics. However, the risk of developing cirrhosis and hepatocellular
      carcinoma may not be so high as it has been stated until now. Interferon alpha is
      at the present time, the only approved drug for the treatment of chronic
      hepatitis C. Its efficiency on criteria such as normalization of
      aminotransferases values or negativation of viremia is obtained in less than 25%
      of patients. The present recommendation is to use 3 MU of interferon alpha, 3
      times per week during 12 months. While interferon leads to improvement of
      histologic lesions, it is not yet proved that a treatment by interferon can
      reduce, years after, the incidence of cirrhosis and hepatocellular carcinoma. No
      therapeutic strategy has been defined yet for the frequent situations of "no
      response", relapses or presence of factors that reduce the efficacy of treatment
      (high initial viremia level, genotype 1b, cirrhosis). It is possible that the
      course of patients having low or no elevation of aminotransferases and/or minimal
      histologic lesions, is good without any treatment. The efficacy of interferon
      alone appears insufficient. Thus trials in progress concern associations of
      antiviral drugs such as vidarabine. In lack of vaccine, preventive treatment is
      essential and depends upon knowledge of conditions of transmission of the virus.
      Transmission through blood and intravenous drug addiction represent 60 to 70% of
      cases of hepatitis C.

PMID- 9033618
TI  - [Liver transplantation in adults. Indications and results].
AB  - Liver transplantation is currently the standard treatment for terminal stage
      liver disease. Overall actuarial survival rate at 5 years is 65 to 70%. However,
      because of the increasing number of transplantations being performed throughout
      the world, the number of potential recipients exceeds the number of donor organs
      available. The long waiting lists thus imply rigorous candidate selection. At the
      same time, the indications for transplantation have evolved. In light of survival
      rates, certain indications, such as hepatitis B with viral replication before
      transplantation or hepatocellular carcinoma less than 3 cm in diameter, may be
      debatable. There are also new indications with excellent short-term results, such
      as alcoholic cirrhosis or hepatitis C cirrhosis. The long waiting lists have led
      to the development of intermediary management schemes: intrahepatic porto
      systemic shunts to decrease portal pressure and facilitate subsequent dissection;
      neoadjuvant chemotherapy for hepatocellular carcinoma; or lamivudin to inhibit B
      virus replication. The limiting factor remains the lack of sufficient donor
      organs. It will not be possible to pursue wider indications unless the number of
      donors can be increased. This objective raises a vital challenge to the medical
      community.

PMID- 9033619
TI  - [Current treatments of congestive heart failure].
AB  - Mortality in patients with congestive heart failure has been assessed in several
      large scale multicentric studies, confirming the therapeutic effect of certain
      treatments and raising questions as to the efficacy of other, sometimes new
      propositions. Conversion enzyme inhibitors are currently considered to be the
      first line treatment for heart failure because of their beneficial effect on
      mortality figures and their capacity to prevent aggravation. These drugs should
      always be prescribed for patients without contraindications, together with
      diuretics when signs of congestion develop, and digitalis in case of non
      response, then finally nitroglycerin. Debate is still open on the effect of beta
      blockers and amiodarone which should be reserved for use by specialists since it
      has not been definitely proven that they can lengthen survival time. Certain
      other drugs have given disappointing results compared with early expectations:
      direct vasodilators, positive inotrops (with the possible exception of
      vesnarinone), and class Ic antiarrhythmics. Finally several drugs in the
      development or research stage may prove to be effective in improving heart
      function, intermediary criteria and, most importantly, survival.

PMID- 9033620
TI  - [Treatment of cytomegalovirus infections in HIV infection].
AB  - Cytomegalovirus (CMV) infections are common in patients with AIDS. Retinal
      localizations predominate, although digestive and neurological and more rarely
      pulmonary localizations are sometimes seen. Functional prognosis is poor in case
      of retinal infection requiring early treatment. Standard therapy is based on
      intravenous administration of two antiviral agents with similar actions:
      ganciclovir and foscarnet. Maintenance therapy, aimed at delaying recurrence, is
      clearly indicated for retinitis and may be so for other localizations. The
      parenteral route is recommended although in case of contraindications, oral
      ganciclovir and local treatments (intravitreal injections, intravireal implants)
      may be used. Recurrence is observed earlier after oral treatment, local
      treatments cannot prevent other localizations and retinal detachment is more
      frequent with vitreal implants. Other drugs are under study. Cygalovir would be
      an interesting alternative due to its long half-life allowing fewer injections.
      Primary prophylaxy for CMV infection is an important perspective. Quantitative
      PCR will help better define risk groups of patients who could benefit from
      preventive therapy. The choice between oral or intravenous administration and the
      correct dose remain to be determined for the most effective preventive treatment
      and to avoid the emergence of resistance.

PMID- 9033621
TI  - [Therapeutic possibilities for the management of vasovagal syncopes].
AB  - Since the advent of the tilt test, our understanding of the pathogenesis of
      vasovagal syncope has progressed greatly. Two mechanisms lead to the sudden fall
      in blood pressure: on one hand a series of interrelated neuroreflexes, and on the
      other, neuroendocrine effects. Although our understanding is not complete, new
      therapeutic measures can be proposed beyond simple empiric prescriptions of
      vagolytic agents. The efficacy of different treatments is yet to be proven due to
      the need for long controlled trials with large numbers of subjects. In the early
      studies versus placebo, no significant evidence of a preventive effect against
      recurrent malaise could be distinguished from the placebo effect. Complementary
      investigations such as the tilt test also act as a placebo. While firm
      recommendations for effective prevention cannot be established until the results
      of controlled trials are available, it is nevertheless possible to propose a
      reasonable approach to management.

PMID- 9033622
TI  - [New pharmacologic approaches to macrolides: example of roxithromycin].
AB  - Macrolides, one of the oldest antibiotic classes, are widely used in out-patient,
      clinics and hospitals. The major improvement in developing newer derivatives
      concerns pharmacokinetic properties. Increased half-lives, persisting
      concentrations in tissues, interstitial fluids and macrophages confer upon newer
      macrolides significant advantages as compared to the parent compound
      erythromycin. Roxithromycin, a newer macrolide has a high peak serum
      concentration, providing very high levels both in the interstitial fluid and
      intracellularly. Pharmacodynamic approaches are still limited with macrolides,
      however the very high inhibitory quotient established for tissue concentrations
      and interstitial fluid suggests the potential clinical efficacy of these drugs.

PMID- 9033623
TI  - Green tea consumption and the risk of pancreatic and colorectal cancers.
AB  - The effect of green tea drinking in reducing human cancer risk is unclear, though
      a protective effect has been reported in numerous animal studies and several
      epidemiologic investigations. Herein the hypothesis that green tea consumption
      may reduce the risk of cancers of the colon, rectum and pancreas is examined in a
      large population-based case-control study conducted in Shanghai, China. Newly
      diagnosed cancer cases (931 colon, 884 rectum and 451 pancreas) during 1990-1993
      among residents 30-74 years of age were included. Controls (n = 1,552) were
      selected among Shanghai residents and frequency-matched to cases by gender and
      age. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of each
      cancer associated with green tea consumption were derived after adjustment for
      age, income, education and cigarette smoking. Additional adjustment for dietary
      items and body size was found to have minimal impact. An inverse association with
      each cancer was observed with increasing amount of green tea consumption, with
      the strongest trends for rectal and pancreatic cancers. For men, compared with
      non-regular tea drinkers, ORs among those in the highest tea consumption category
      (> or = 300 g/month) were 0.82 for colon cancer, 0.72 for rectal cancer and 0.63
      for pancreatic cancer, with p values for trend being 0.38, 0.04 and 0.04,
      respectively. For women, the respective ORs for the highest consumption category
      (> or = 200 g/month) were 0.67, 0.57 and 0.53, with the respective p values for
      trend being 0.07, 0.001 and 0.008. Our findings provide further evidence that
      green tea drinking may lower the risk of colorectal and pancreatic cancers.

PMID- 9033624
TI  - Tobacco use and colon cancer.
AB  - Smoking cigarettes has been consistently associated with adenomatous polyps.
      However, only a few studies have reported associations between smoking cigarettes
      or using other forms of tobacco and colon cancer. A population-based case-control
      study of colon cancer was conducted in 3 areas in the United States: northern
      California, Utah and Minnesota. We observed approximately a 50% increase in colon
      cancer risk from smoking over a pack of cigarettes per day among both men and
      women. Those who stopped smoking remained at increased risk, even if they stopped
      over 10 years ago. Our data suggest that the amount smoked may be a more
      important factor than the total number of years smoked. Smoking neither cigars
      nor pipes was associated with an increased risk of colon cancer. Among female
      participants only, those who smoked over 20 cigarettes per day and had a large
      body mass index were at greater risk of colon cancer than participants who smoked
      the same amount but were smaller (p for interaction among women = 0.04).

PMID- 9033625
TI  - Possible relation between hypertension and cancers of the renal pelvis and
      ureter.
AB  - To evaluate the relationship of selected medical conditions and medications with
      cancers of the renal pelvis and ureter, we interviewed 308 subjects with renal
      pelvis cancer, 194 subjects with ureter cancer and 496 control subjects in 3
      areas of the United States. After controlling for the effects of smoking, age,
      gender and geographic residence, a history of hypertension (reported to have been
      diagnosed more than 5 years before interview) was associated with a small but
      significantly increased risk (odds ratio [OR] = 1.3; 95% confidence interval
      [CI], 1.0-1.8), whereas no relationship was observed with a variety of other
      medical conditions or medications. Stratified analysis showed that the risk
      associated with hypertension was twice as high among users of diuretics or other
      antihypertensive drugs (OR = 2.4; 95% CI, 1.1-4.9) as it was among those who
      never used these medications (OR = 1.2; 95% CI, 0.8-1.7). Our findings suggest
      that the association previously reported between hypertension and renal cell
      cancer may extend to cancers of the renal pelvis and ureter.

PMID- 9033626
TI  - A phase-I clinical study of autologous tumor cells plus interleukin-2-gene
      transfected allogeneic fibroblasts as a vaccine in patients with cancer.
AB  - Tumor cells transfected to express immunostimulatory cytokines, or admixed with
      similarly modified bystander cells, are able to induce immune responses against
      unmodified tumor cells in animal models. For treatment of human patients, a
      vaccine composed of autologous tumor cells and IL-2-secreting allogeneic
      fibroblasts was developed. Autologous tumor cells were isolated from biopsy
      specimens. A clone (KMST 6.14) of an immortalized human fibroblast line that
      stably secreted 5290 IU IL-2 per 10(6) cells and per 24 hr was obtained by
      cationic lipofection with an expression construct for human IL-2 and Neo(r).
      Fifteen patients with refractory malignant tumors received 3-4 injections of
      irradiated KMST6.14 and autologous tumor cells in a phase-I clinical trial.
      Increasing transient inflammatory responses without systemic toxicity developed
      at vaccination sites and after injections with irradiated tumor cells only (p <
      0.05). These sites contained a dense infiltrate of CD3+ T cells with numbers of
      CD4+ helper cells exceeding those of CD8+ cytotoxic T cells (CTL). CD8+ T-cell
      lines isolated from vaccination sites of 2 malignant melanoma patients but not of
      renal-cell carcinoma patients exhibited a dominant lytic activity against
      autologous tumor cells in vitro. CD8+ T-cell clones established from the
      vaccination site of 1 of 2 renal-cell carcinoma patients preferentially lysed
      autologous and partially matched allogeneic renal-cell carcinoma cells. In
      conclusion, a vaccine composed of IL-2 gene-transfected allogeneic fibroblasts
      and autologous tumor cells is able to enhance specific anti-tumor T-cell
      responses in vivo without major side-effects. Malignant melanoma and renal-cell
      carcinoma appear to be promising entities for testing of similar approaches in
      future therapeutic trials.

PMID- 9033627
TI  - Endometrial cancer in relation to intra-uterine device use.
AB  - Data from a population-based case-control study were used to evaluate the risk of
      endometrial cancer among women who have used an intra-uterine device (IUD).
      Incident cases were identified between 1985 and 1991 among women aged 45-74 years
      who were residents of one of 3 counties in Washington State. Controls were
      selected by random digit dialing, and both groups of subjects received an in
      person detailed interview. In this study population, women who had ever used an
      IUD were estimated to have a risk of endometrial cancer that was 0.61 times that
      of other women (95% CI 0.41-0.89). The reduction in cancer risk was not found to
      be dependent on duration of IUD use. There was a suggestion that women who had
      used intra-uterine contraception relatively late in reproductive life experienced
      a greater reduction in risk than those whose use was more distant or at a younger
      age. The relative risk among the small number of women who were currently using
      an IUD was 0.49 (95% CI 0.12-2.80). These results apply to the use of inert and
      copper IUDs as there was no use of progestin-releasing IUDs among women in the
      study population. The data from this and several other studies of the question
      support the hypothesis that use of an IUD has a favorable effect on the
      subsequent risk of endometrial cancer. The reason(s) for such a reduced risk is
      unclear.

PMID- 9033628
TI  - Karyotypic abnormalities in fibroadenomas of the breast.
AB  - Short-term cultures of 50 fibroadenomas of the breast were cytogenetically
      analyzed. Nine tumors were found to display clonal chromosome aberrations. One
      had multiple, cytogenetically unrelated clones, whereas the others had a single
      abnormal clone each. Four cases had one balanced translocation as the sole
      anomaly, and one had a complex intrachromosomal rearrangement of chromosome 3,
      leading to loss of 3p material. One fibroadenoma had a single numerical
      aberration, and one had supernumerary ring chromosomes. The remaining 2 cases had
      both numerical and structural aberrations. The only recurrent alterations were
      trisomy 20 and rearrangement of chromosome arm 1p. The finding of similar
      chromosomal aberrations in fibroadenomas and carcinomas suggests that women with
      karyotypically abnormal fibroadenomas may have an increased risk of developing
      subsequent breast cancer. If so, different chromosome anomalies might have
      different pathogenetic and/or prognostic significance.

PMID- 9033629
TI  - Detection of MAGE-4 protein in sera of patients with head-and-neck squamous-cell
      carcinoma.
AB  - The MAGE-4 gene, a member of the MAGE gene family, is expressed in various
      cancers, including head-and-neck squamous-cell carcinomas (HN-SCC), but is not
      expressed in any normal tissues except for the testis and placenta. The aim of
      this study was to determine whether serum MAGE-4 protein is a useful tumor marker
      for detection of HN-SCC. An enzyme-linked immunosorbent assay was used to measure
      serum level of MAGE-4 protein. The serum level of MAGE-4 in pre-operative HN-SCC
      patients was significantly higher than that in patients with non-malignant
      diseases (NMD) of the head and neck, volunteers undergoing cancer screening
      (VOL), or healthy donors (HD). When the cut-off level was determined at 1.15
      ng/ml (mean plus 3 SD of HD), sera from 28 of 96 patients with HN-SCC (p < 0.0001
      vs. the other groups), 7 of 82 patients with NMD, 2 of 92 with VOL, and 0 of 68
      HD were positive for MAGE-4. Serum levels of MAGE-4 protein in all 7 HN-SCC
      patients whose sera were positive for MAGE-4 before operation decreased after
      operation, and, in one patient, a renewed rise in serum level was followed by
      recurrence. These results indicate that MAGE-4 protein is detectable in sera of a
      significant number of HN-SCC patients, and that serum MAGE-4 protein might be a
      useful tumor marker to monitor the recurrence of MAGE-4-positive HN-SCC.

PMID- 9033630
TI  - Different points of action of retinoids and anti-estrogens in G1 phase identified
      in synchronized T-47D breast cancer cells.
AB  - Both retinoids and anti-estrogens inhibit breast cancer cell proliferation with
      accumulation of cells in the G1 phase of the cell cycle, but the effect of
      retinoids is delayed compared to that of anti-estrogens. To determine whether
      this temporal difference is due to a simple delay in the action of retinoids on a
      common site or to different sites of action within the G1 phase, we studied the
      cell cycle effects of retinoic acid (RA) and the anti-estrogen ICI 164384 (ICI)
      in T-47D cells partially synchronized by mevalonic acid rescue of lovastatin
      induced cell cycle arrest. We found that cells entering the cell cycle semi
      synchronously after mevalonic acid rescue of lovastatin treatment were
      immediately susceptible to ICI but not RA. This suggests that RA may act at a
      point up-stream and ICI at a point down-stream of lovastatin action. Consistent
      with this, cells recommencing cell cycle progression after RA treatment were
      susceptible to the effects of lovastatin, while cells pre-treated with ICI then
      rescued with estradiol were not. In addition, cells rescued from cell cycle
      arrest induced by either RA, ICI or lovastatin entered S phase with the same
      kinetics. Our findings suggest, first, that within G1, RA acts before and ICI
      acts after the point of lovastatin action and, second, that despite these
      differences in the initiation of cell cycle arrest, the final nature of the cell
      cycle arrest is similar. Hence, retinoids and anti-estrogens may be expected to
      target different cell cycle-regulatory molecules to initiate cell cycle arrest,
      while overcoming this arrest may be accomplished by the activation of a common
      molecular pathway.

PMID- 9033631
TI  - Anti-neoplastic activity of paclitaxel on experimental superficial bladder
      cancer: in vivo and in vitro studies.
AB  - The effects of intravesical administration of paclitaxel (taxol) in a bladder
      tumor model in mice, as well as the drug's in vitro activity on the same tumor
      cells, have been studied. Two cell lines, derived from MBT-2 cells, were employed
      in these experiments. The T50 line (obtained by many passages in mice) was much
      more aggressive in vivo than the T5 line. In vivo paclitaxel treatment for 3 days
      after T5 implantation resulted in a considerable retardation of tumor growth,
      whereas under the same conditions the T50 line was much less, although still
      significantly, affected. When treatment was started 1 day after tumor
      implantation, both tumor variants were affected by paclitaxel to the same extent.
      The in vitro experiments utilized the MiCK assay, which allows continuous
      recording of the kinetics of cell growth. These studies revealed a 39.8%
      inhibition of cell growth by 2.10(-8)M paclitaxel in the T50 line and a 30-fold
      increase in concentration had only a small additional effect on the degree of
      inhibition. At 2.10(-8)M paclitaxel, growth of T5 was inhibited by 21.7%, which
      increased to 35.2% at 6.10(-7)M. The treated cells displayed bundles of
      microtubuli, as described for other paclitaxel-treated cells.

PMID- 9033632
TI  - Analogues of CTL epitopes with improved MHC class-I binding capacity elicit anti
      melanoma CTL recognizing the wild-type epitope.
AB  - The MHC class-I binding affinity of an epitope is an important parameter
      determining the immunogenicity of the peptide-MHC complex. In order to improve
      the immunogenicity of an epitope derived from melanocyte lineage-specific antigen
      gp100, we performed amino-acid substitutions within the epitope and assayed both
      HLA-A*0201 binding and CTL recognition. Anchor replacements towards the HLA
      A*0201 peptide-binding motif gave rise to peptides with higher HLA-A*0201 binding
      capacity compared to the wild-type epitope. In addition, several of the gp100 154
      162 epitope-analogues were more efficient at target-cell sensitization for lysis
      by anti-gp100 154-162 CTL compared to the wild-type epitope. These altered gp100
      154-162 epitopes were subsequently tested for their capacity to induce CTL
      responses in vivo using HLA-A*0201/Kb transgenic mice, and in vitro using HLA
      A*0201 + donor-derived lymphocytes. Interestingly, the peptide-specific CTL
      obtained, which were raised against the different gp100 154-162 epitope
      analogues, displayed cross-reactivity with target cells endogenously processing
      and presenting the native epitope. These data demonstrate that altered epitopes
      can be exploited to elicit native epitope-reactive CTL. The use of epitope
      analogues with improved immunogenicity may contribute to the development of CTL
      epitope based vaccines in viral disease and cancer.

PMID- 9033633
TI  - Differential targeting and processing of procathepsin D in normal and transformed
      murine 3T3 fibroblasts.
AB  - The kinetics of transport and the processing of procathepsin D (proCD), the
      precursor of a lysosomal aspartyl protease involved in tumor-cell proliferation
      and metastasis, were compared in normal and SV-40- or benzo[a]pyrene-transformed
      3T3 mouse fibroblasts. Sorting of newly synthesized proCD in normal cells was
      almost complete within 3 hr, while in transformed cells a fraction of the
      precursor survives a long time. In both normal and transformed 3T3 cultures,
      secretion of proCD started at 3 hr of chase. However, in normal cells secretion
      of proCD remained constant between 3 and 24 hr of chase, while in transformed
      cells it increased along with the chase incubation. The efficiency of formation
      of the mannose-6-phosphate group on proCD varied among the 3 cell types, being
      minimal in benzo[a]pyrene-transformed 3T3 cells. Ammonium chloride, a drug known
      to disrupt the segregation and to enhance the secretion of lysosomal proenzymes,
      was 2-fold more effective in normal than in transformed 3T3 cells. Despite
      vacuolar alkalinization, about one third of proCD was segregated into the
      endosomal-lysosomal pathway in normal and in transformed 3T3 fibroblasts,
      indicating the existence in these cells of alternative, mannose-6-phosphate
      receptor-independent mechanisms for targeting proCD. Thus, while hypersecretion
      of proCD and reduced sensitivity to vacuolar alkalinization are common features
      of both transformed cell types, the mechanisms responsible for inefficient
      segregation of proCD may differ between virally and chemically transformed 3T3
      cells.

PMID- 9033634
TI  - Internalization of indium-labeled LDL through a lipid chelating anchor in human
      pancreatic-cancer cells as a potential radiopharmaceutical for tumor
      localization.
AB  - Low-density lipoproteins (LDL) labeled with indium via a lipid-chelating agent,
      the bis(stearylamide) of diethylenetri-aminepentaacetic acid (L), were evaluated
      as a potential radiopharmaceutical (111In-L-LDL) for tumor localization by
      studying their internalization in human pancreatic cancer cells (Capan-1). Using
      Dil-LDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate
      LDL), this cell line was shown to bind human LDL with a high-affinity saturable
      component and a low-affinity non-saturable (40%) component. The single saturable
      high-affinity binding site had a KD of 27.5 +/- 2.1 micrograms/ml and a maximal
      binding of 610 +/- 7.5 ng/ml protein. Electron-microscopic examination of the In
      L-LDL particles revealed the peripheral distribution of the electron-dense indium
      atoms at the outer surface of LDL. The modified LDL were then shown to be
      internalized by the cells. After conjugation of In-L-LDL to colloidal gold to
      follow the different stages of internalization, electron-microscopic examination
      showed that the In-L-LDL gold conjugates were stuck to the external sheet of the
      plasma apical and microvilli membrane, into earlier and later endosomes and into
      multivesicular bodies, suggesting the penetration of the In-L-LDL particles into
      lysosomal vacuoles. The observation of In-L-LDL-gold conjugates in deep-seated
      cytoplasm suggests that LDL could be employed as a drug-transport vehicle for
      targeting cytotoxics or radionuclides close to the cell nucleus.

PMID- 9033635
TI  - Reduction in the duration of myelotoxicity associated with radioimmunotherapy
      with infusions of the hemoregulatory peptide, HP5b in mice.
AB  - The hemoregulatory peptide, pGlu-Glu-Asp-Cys-Lys (pEEDCK or HP5b), has been shown
      to reversibly inhibit the proliferation of bone-marrow progenitor cells, and has
      been reported to protect mice from the myelotoxicity associated with ara-C, a
      chemotherapeutic agent. We undertook to use this reagent to reduce
      radioimmunotherapy(RAIT)-associated bone-marrow toxicity by suppressing
      hematopoiesis during the critical period when bone marrow is exposed to
      radiation. The reported studies optimize the use of HP5b to reduce the duration
      of neutropenia and thrombocytopenia. We found that 3.6 micrograms/day of HP5b
      administered through a continuous 7d mini-osmotic pump, together with a bolus
      dose of 3.6 micrograms 3 hours before the radioantibody dose, gave the best
      effect, as measured by neutrophil counts on day 28 post RAIT. With sub-lethal
      doses of RAIT, the period of neutropenia was reduced by 2 weeks, and there
      appeared to be more rapid recovery of morphologically mature myeloid cells. The
      peptide, however, does not appear to alleviate the lymphotoxicity associated with
      RAIT. No adverse effects have been noted from continuous infusions of the
      peptide. In the past, we reported that cytokines (IL-I/GM-CSF) are not marrow
      restorative when given after RAIT. However, an additive effect is observed when
      HP5b infusions are combined with post-RAIT cytokine administration, suggesting
      that a significant pool of bone-marrow progenitor cells remains when HP5b is co
      administered with RAIT. Thus, HP5b is an alternate approach to reducing
      myelotoxicity, and may be used in combination with cytokines to further reduce
      the duration of myelosuppression.

PMID- 9033636
TI  - Effects of thymectomy and tolerance induction on tumor immunity in adult Xenopus
      laevis.
AB  - Major-histocompatibility-complex homozygous partially inbred adults of the ff
      strain of Xenopus reject transplants of tumor cells of ff strain origin; ff
      tadpoles do not. Thymectomy, performed 5 days after fertilization, abrogated the
      adult tumor-rejection response suggesting that in this system tumor rejection is
      immunologically mediated by T cells. Thymectomy later in larval life did not
      alter tumor rejection, but it did reduce T-cell numbers. Tolerance to minor
      histocompatibility(H) antigens segregating within the ff family, which was
      induced by grafting adult skin to metamorphosing larvae, did not affect the tumor
      rejection capacity of the tolerant adult hosts. This suggests that the ff-2 tumor
      expresses (a) tumor-specific antigen(s). Immunization of larvae with tumor cells
      did not induce tolerance to skin grafts transplanted during adult life. Indeed,
      such grafts were rejected in accelerated fashion, suggesting that memory cells
      generated in the larvae persist through metamorphosis.

PMID- 9033637
TI  - CPT-11 in human colon-cancer cell lines and xenografts: characterization of
      cellular sensitivity determinants.
AB  - CPT-11, a new semisynthetic derivative of camptothecin, is active in a number of
      tumor types in the clinic, including colon cancer. CPT-11 is a drug that is
      converted into the active metabolite SN-38 by a carboxylesterase. Experiments
      were performed to obtain more insight in the cellular characteristics in 5
      unselected human colon-cancer cell lines that account for the differential
      sensitivity to CPT-11 and SN-38. In vitro, the sensitivity to CPT-11 and SN-38
      was highest in LS174T and COLO 320 cells, intermediate in SW1398 cells and lowest
      in COLO 205 and WiDr cells. SN-38 was 130 to 570 times more active than CPT-11.
      CPT-11 induced complete remissions in 6 out of 12 COLO 320 tumors grown as
      subcutaneous xenografts, but was not effective in WiDr tumors. The cellular
      carboxylesterase activity did not relate to the sensitivity to CPT-11. The enzyme
      activity was higher in normal mouse tissues, i.e., serum and liver, than in COLO
      320 or WiDr xenografts, indicating that tumor carboxylesterase is of minor
      importance for CPT-11 efficacy. The topoisomerase-1 mRNA expression in tumor
      cells was not predictive of the antiproliferative effects of CPT-11 or SN-38. We
      observed a positive relationship between the DNA topoisomerase-1 activity and the
      cellular sensitivity to carboxylesterase-activated CPT-11 (r = 0.75, p < 0.1) as
      well as to SN-38 (r = 0.89, p < 0.05). The higher topoisomerase-1 activity in
      COLO 320 cells and tumors when compared with that in WiDr cells and tumors
      reflected the differences in sensitivity to the drug(s). In conclusion, the DNA
      topoisomerase-1 activity was the best determinant for CPT-11/SN-38 sensitivity in
      this panel of unselected human colon-cancer cell lines.

PMID- 9033638
TI  - bcl-2 over-expression delays radiation-induced apoptosis without affecting the
      clonogenic survival of human prostate cancer cells.
AB  - In this study we evaluated the effect of over-expression of the bcl-2 gene, a
      potent apoptosis suppressor, on radiation-induced apoptotic cell death in 2 human
      prostate cancer cell lines, androgen-independent PC-3 cells and androgen
      sensitive LNCaP cells. Cells were transfected with the bcl-2 gene and bcl-2
      transfectant clones isolated under neomycin selection; bcl-2 gene integration and
      level of mRNA and protein expression in the cloned transfectants were examined by
      Southern, Northern and Western blot analyses, respectively. Parental, neo control
      and bcl-2-expressing cells were exposed to single or fractionated doses of
      ionizing irradiation, and the cellular response to radiation was determined at
      24, 48 and 72 hr post-irradiation, on the basis of: (i) loss of cell viability,
      (ii) clonogenic survival and (iii) induction of apoptotic DNA fragmentation. At
      24 hr post-irradiation all cell lines, i.e., parental and bcl-2 transfectants,
      failed to form colonies, though the majority of bcl-2-expressing cells did not
      exhibit apoptotic morphology; bcl-2 over-expression in both cell lines reduced
      apoptosis 48 hr post-irradiation from 20-25% to 5% at a dose of 2,000 cGy. By 72
      hr, bcl-2 over-expression afforded a 3-fold protection from radiation-induced
      apoptosis. There was no significant difference, however, in the clonogenic
      survival of the parental and bcl-2-expressing cells. Furthermore, there was a 24
      hr delay in induction of the apoptosis marker gene SGP-2/TRPM-2 in the bcl-2
      expressing cells, co-incidental with the delay in apoptotic DNA fragmentation.

PMID- 9033639
TI  - The expression of mouse gene P1A in testis does not prevent safe induction of
      cytolytic T cells against a P1A-encoded tumor antigen.
AB  - Tumor antigen P815AB is recognized by cytolytic T lymphocytes (CTL) on mouse
      mastocytoma P815. This antigen is encoded by P1A, a gene activated in several
      tumors but silent in normal tissues except for testis and placenta.
      Notwithstanding the expression of P1A in testis, we found that male mice mounted
      P815AB-specific CTL responses as efficiently as females. The responding males
      remained fertile and no autoimmune lesions were observed in their testes. By
      immunohistochemistry with a rabbit antiserum directed against the P1A protein, we
      identified spermatogonia as the testicular cells expressing P1A. The absence of
      MHC class-I molecules on spermatogonia could be one of the mechanisms of
      protection against testicular autoimmunity, as the antigenic peptide should not
      be displayed at the cell surface. Human genes MAGE, BAGE and GAGE, which also
      code for tumor antigens recognized by autologous CTL, are not expressed in normal
      tissues other than testis. The results obtained in mice with antigen P815AB
      suggest that immunization of human males with such antigens will not generate
      autoimmune side-effects. Although P1A is strongly expressed in placenta, we also
      found that gestation did not prevent generation of CTL responses against antigen
      P815AB, and that such CTL responses did not affect gestation outcome. We
      identified labyrinthine trophoblasts as the placental cells expressing P1A.
      Again, the absence of MHC class-I molecules on these cells provides a plausible
      explanation for placental protection, although other mechanisms may also play a
      role.

PMID- 9033640
TI  - Differential effects of polyunsaturated fatty acids on chemosensitivity of NIH3T3
      cells and its transformants.
AB  - Polyunsaturated fatty acids (PUFAs) have been suggested, on the basis of animal
      model studies, to be related not only to cancer development but also to
      chemotherapeutic effects. Controversy persists, however, as to which types of
      PUFAs are beneficial in terms of chemosensitivity. In this study, we used the
      NIH3T3 cell line and its SIC(sigmoid colon cancer)-oncogene transformants to
      investigate the effects of PUFAs on the chemosensitivity of non-malignant and
      malignant cells in terms of cell proliferation. We also determined the fatty-acid
      composition of cells by high-performance liquid chromatography (HPLC). The
      results revealed that the sensitivity of SIC transformants to mitomycin C (MC)
      was lower than that of NIH3T3 cells cultured in 10% calf-serum DMEM without PUFA
      supplementation. When cells were cultured in DMEM supplemented with
      eicosapentaenoic acid (EPA) at a concentration (2 micrograms/ml) that does not
      influence cell proliferation, the sensitivity of SIC transformants to MC
      increased, whereas that of NIH3T3 cells decreased in comparison with the
      sensitivity of cells cultured without PUFA supplementation (p < 0.05). There was
      no difference between the 2 cell lines in the chemosensitivity of cells cultured
      in medium supplemented with arachidonic acid (ARA). The SIC transformants
      contained more stearic acid (C:18) and less lauric acid (C:12) than NIH3T3 cells
      cultured without PUFA. Culturing the cells in medium supplemented with EPA or ARA
      modified the cellular fatty-acid composition. EPA caused the relative combined
      percentage of lauric acid and myristic acid (C:14) in SIC transformants to
      decrease significantly, and the SIC transformants tended to accumulate additional
      EPA, in contrast to the NIH3T3 cells. We conclude that the alterations in fatty
      acid composition in malignant transformants caused by exogenous EPA differ from
      those in non-malignant cells, and that these changes account for the increased
      chemosensitivity of malignant transformants. Although preliminary, these findings
      imply that EPA specifically enhances the chemosensitivity of malignant cells.

PMID- 9033641
TI  - Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell
      response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice.
AB  - We investigated both the effect and the mechanism of oral (p.o.) administration
      of PSK, a protein-bound polysaccharide derived from Basidiomycetes, on the anti
      tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o.
      administration of PSK significantly suppressed the growth of colon 26 carcinoma
      (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented
      the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells.
      PSK treatment also significantly decreased the levels of immunosuppressive
      factors such as plasma transforming growth factor (TGF)-beta in the i.c. C-26
      inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor
      T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815).
      The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored
      the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN
      cells against in vitro restimulation. Furthermore, the treatment also decreased
      the TGF-beta production but increased the IFN-gamma production of these cells.
      The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell
      dependent cytolytic activity of the draining mesenteric LN cells after in vitro
      restimulation. Overall, these results indicate that the p.o. administration of
      PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly
      through a suppression of TGF-beta production and a restoration of IFN-gamma
      production.

PMID- 9033642
TI  - Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in
      international data.
AB  - Hodgkin's disease (HD) has long been suspected to have an infectious precursor,
      and indirect evidence has implicated Epstein-Barr virus (EBV), a ubiquitous
      herpesvirus, as a causal agent. Recent molecular studies using EBER in situ
      hybridization or latency membrane protein-I (LMP-I) immunohistochemistry have
      identified EBV latent infection in up to 50% of HD tumors. However, the
      epidemiologic features of these cases have not been examined in detail. To
      explore the epidemiology of EBV-positive HD so as to understand the role of EBV
      in HD etiology more clearly, this project accumulated patient data from 14
      studies that had applied these EBV assays to HD tumors. With information on age
      at diagnosis, sex, ethnicity, histologic subtype, country of residence, clinical
      stage and EBV tumor status from 1,546 HD patients, we examined risk for EBV
      positive disease using logistic regression. Forty percent of subjects had EBV
      positive tumors, and EBV prevalence varied significantly across groups defined by
      the study variables. Odds ratios (OR) for EBV-associated HD were significantly
      elevated for Hispanics vs. whites (OR = 4.1), mixed cellularity vs. nodular
      sclerosis histologic subtypes (OR = 7.3, 13.4, 4.9 for ages 0-14, 15-49, 50+
      years), children from economically less-developed vs. more-developed regions and
      young adult males vs. females (OR = 2.5). These findings suggest that age, sex,
      ethnicity and the physiologic effects of poverty may represent biologic modifiers
      of the EBV association and confirm that this association is strongly but variably
      linked to histologic subtype. The data augment biologic evidence that EBV is
      actively involved in HD pathogenesis in some cases but describe epidemiologic
      complexity in this process.

PMID- 9033643
TI  - Binding, internalization and degradation of EGF-dextran conjugates in two human
      bladder-cancer cell lines.
AB  - Bladder carcinomas often have an increased number of epidermal growth factor
      (EGF) receptors. The EGF receptors can, in these cases, be targets for toxic
      conjugates. In this study, EGF-dextran conjugates were used as targeting agents
      with therapeutic potential. The binding, internalization and degradation of 125I
      EGF-dextran conjugates in J82 and RT4, 2 different bladder cancer cell lines,
      were investigated. The behaviour of 125I-EGF was studied as a comparison. The
      125I-EGF-dextran showed a continuous increase in binding up to 24 hr, while 125I
      EGF exhibited maximum binding after about 90 min. Both cell lines showed similar
      binding patterns. The binding of 125I-EGF-dextran and 125I-EGF was, on both cell
      lines, receptor-specific since the binding could be displaced with non
      radioactive EGF. Analysis of internalized and membrane-bound 125I activity after
      administration of 125I-EGF-dextran showed that most of the activity was membrane
      bound. A large part of both the internalized and the membrane-bound activity
      remained cell-associated up to 24 hr. The internalized and membrane-bound
      activity after administration of 125I-EGF decreased rapidly and only a small
      fraction remained cell-associated after 24 hr. 125I-EGF-dextran remained cell
      associated, with only a limited release of low- and high-molecular-weight
      radioactivity throughout the 24-hr period, while 125I-EGF was extensively
      degraded and released into the incubation medium as low-molecular-weight
      radioactivity during this time. Several qualities of the 125I-EGF-dextran
      conjugates might be favourable for targeted radiotherapy.

PMID- 9033644
TI  - Mutations of the Ki-ras, p53 and APC genes in adenocarcinomas of the human small
      intestine.
AB  - In contrast to the origins of colorectal carcinomas, the mechanisms of
      carcinogenesis in the small intestine remain unclear. We therefore analyzed the
      mutational status of the Ki-ras, p53, and adenomatous polyposis coli (APC) genes
      in primary carcinomas of the small intestine and compared the mutation patterns
      with those established for colorectal cancers. DNA was extracted from 15 formalin
      fixed, paraffin-embedded lesions. Codons 12, 13 and 61 of the Ki-ras gene, exons
      5-8 of the p53 gene, and codons 1268-1569, which contain the mutation cluster
      region (MCR) of the APC gene, were amplified by means of PCR, subcloned and
      sequenced. Mutations of the Ki-ras and p53 genes were observed in 8 (53.3%) and 4
      lesions (26.7%), respectively. The mutational frequency of the Ki-ras gene in the
      present series of small intestinal carcinomas was similar, while that of the p53
      gene was slightly lower than the reported frequencies for colorectal carcinomas.
      Only one case showed a mutation of the APC gene, involving an insertional
      mutation of an adenine at codons 1554-1556 with formation of a stop codon
      immediately downstream. Since the occurrence of an APC mutation is considered an
      early event in colorectal carcinogenesis, our findings indicating an extremely
      low frequency of such changes in and around the MCR suggest that carcinomas of
      the small intestine arise via a genetic pathway distinct from that involved in
      the development of carcinomas of the colorectum.

PMID- 9033645
TI  - Occult epithelial tumor cells detected in bone marrow by an enzyme immunoassay
      specific for cytokeratin 19.
AB  - The presence of isolated carcinoma cells detected immunocytochemically in bone
      marrow has been shown to be of prognostic relevance for cancer patients.
      Unfortunately, the immunocytochemical method (ICC) is laborious and depends on
      the subjective interpretation of the individual investigator. Therefore, an
      immunoassay was designed for detection of cytokeratin 19 (CK19). By analyzing
      blood samples from 52 healthy volunteers and 40 bone-marrow aspirates from
      control patients, a cut-off point of 250 pg/ml CK19 was determined. Application
      of this cut-off point enabled a specificity of 95% to be shown for bone marrow
      and of nearly 100% for venous blood. The assay detected 10 HT-29 colon-carcinoma
      cells among 5 x 10(6) peripheral-blood leukocytes. In comparison with controls,
      bone-marrow samples of cancer patients were found to have significantly elevated
      levels of CK19 (p < 0.05). In the analysis of 386 marrow aspirates of cancer
      patients, a significant concordance of ELISA and ICC was observed (chi 2 = 18.3;
      p < 0.001). Both procedures, nevertheless, differed in 147 (38%) samples, of
      which more than two thirds (101) were only ELISA-positive. The CK status detected
      by ELISA did not correlate with the TNM stage and the histological grading. The
      established immunoassay allowed sensitive and specific detection of disseminated
      epithelial tumor cells and appeared to be faster, less laborious and more
      objective than ICC. Follow-up studies are required to assess the prognostic
      relevance of this ELISA before it can be applied as a routine method for
      monitoring of minimal residual epithelial cancer.

PMID- 9033646
TI  - Use of multiple primary cancers to indicate associations between smoking and
      cancer incidence: an analysis of 500,000 cancer cases diagnosed in Norway during
      1953-93.
AB  - The occurrence of multiple primary cancers is relatively rare, but may provide
      indications of common or opposite risk factors for different types of cancer. In
      the present study, the occurrence of multiple primary cancers was used to
      indicate possible associations between smoking and the incidence of cancers other
      than those generally accepted as smoking-associated. All cancer cases in persons
      above the age of 30, registered at the population-based Cancer Registry of Norway
      (1953-1993), were used in the analysis. For each type of cancer, the observed
      occurrence of smoking-associated cancers in the patients was compared with the
      expected occurrence if the patients had the same risk as the general population.
      Similar comparisons were made for the occurrence of other cancers in patients
      with a smoking-associated cancer. The results were presented as standardized
      incidence ratio (SIR), the ratio of the observed and the expected numbers of
      cases. The results indicated that uterine cervical cancer may share some
      important risk factor(s) with the cancers generally accepted as smoking
      associated. This is in accordance with the literature, where an association
      between smoking and uterine cervical cancer has been found consistently. In
      addition, the results for liver cancer and leukemia indicated that these types of
      cancer also share some risk factor(s) with the smoking-associated cancers.

PMID- 9033647
TI  - Human papillomavirus types 52 and 58 are prevalent in cervical cancers from
      Chinese women.
AB  - A substantial body of evidence has confirmed human papillomavirus (HPV) infection
      as an etiologic agent in human cervical cancer. To evaluate the association
      between HPV and cervical cancer in Chinese women, we examined tumor specimens
      from women who lived in Shanghai, People's Republic of China. Biopsies from 40
      women, diagnosed with either squamous-cell carcinoma (n = 35) or adenocarcinoma
      (n = 5) were tested for HPV DNA by PCR. The HPV types present in tumors were
      determined either by hybridization of PCR products with HPV type-specific probes
      or by PCR-based sequencing. A total of 35 of the 40 cervical cancer specimens
      (87.5%) contained HPV DNA. The following distribution and types were detected:
      7.5% HPV 16, 10% HPV 18, 20% HPVs 16 and 18, 15% HPV 52, 15% HPV 58, 12.5% HPVs
      52 and 58 and 7.5% unclassified HPVs. In this population of Chinese women with
      cervical cancer, HPV 52 and 58 were as prevalent as the "high-risk" (for cervical
      cancer) viruses HPVs 16 and 18.

PMID- 9033648
TI  - Rare alleles at different VNTR loci among lung-cancer patients with
      microsatellite instability in tumours.
AB  - Work in our laboratory has shown a significantly higher frequency of
      microsatellite mutations in tumours from lung-cancer patients with rare alleles
      at the HrasI VNTR locus compared with those with common alleles. In 137 lung
      cancer patients, the association between microsatellite instability and rare
      alleles at the HrasI VNTR locus was confirmed with 17 microsatellite markers. We
      found a significant association between LOH in lung tumours of marker D3s966 with
      microsatellite instability. In samples with LOH at marker D3s966 (3p21.3) 22% of
      loci tested showed instability, whereas 8% showed instability without LOH at
      D3s966. To investigate whether rare alleles at the HrasI locus are linked to rare
      alleles at other loci, a second minisatellite (D17S4) was genotyped. In a
      population of 406, 4 individuals with D 17S4 rare alleles were detected of whom 3
      also had rare alleles at the HrasI VNTR locus. The probability of this
      association to occur by chance is low. Thus, rare alleles at the HrasI locus may
      be associated with rare alleles at other loci, and could be an indication of
      germline instability. The findings indicate that microsatellite instability in
      lung tumours is not strictly associated with features in the HrasI proto
      oncogene, but may be the result of the same mechanism(s) that generate(s) new
      alleles at the HrasI and D17S4 loci.

PMID- 9033649
TI  - The anti-tumoral activity of human glycoprotein HGP.92: a study with the mouse
      Lewis-lung-tumor cell.
AB  - The ability of a purified human glycoprotein (HGP.92) to exert anti-tumor
      activity was investigated in a mouse model using long-term readout assays. In
      vitro, in the presence of inflammatory mouse macrophages incubated with HGP.92,
      the growth of the mouse Lewis-lung-tumor cells (3LL) was decreased. This effect
      was concentration-dependent and required direct contact between tumor targets and
      HGP.92-treated macrophages. In addition, if the macrophage monolayer was depleted
      of HGP.92 before addition of the target cells, no more cytostatic effect was
      observed. This anti-tumor activity of HGP.92-treated mouse macrophage was
      partially abrogated by addition of catalase in the culture medium, but not by
      superoxide dismutase or scavengers of the hydroxyl radical and singlet oxygen.
      Moreover, this tumor-cell growth reduction was not dependent on nitric oxide. In
      vivo, multiple i.v. injections of HGP.92 (5 times, 3 days apart) during the first
      week and a half exerted significant anti-tumor activity, as assessed by the
      reduction of both the number and the size of the lung nodules 3 weeks after i.v.
      inoculation of 3LL cells.

PMID- 9033650
TI  - Quantitative changes in cytoskeletal and nuclear actins during cellular
      transformation.
AB  - Actin, a highly conserved protein comprising cell stress fibers and other
      cellular structures, is found in both the cytoplasm and nucleus of cells and
      responds to both epigenetic signals and altered gene expression occurring during
      tumorigenesis. We have previously shown that changes in the cytoplasmic F- and G
      actin ratios reflect bladder cancer risk. To determine whether nuclear actin is
      also altered and how nuclear and cytoplasmic actin alterations are interrelated
      in transformation, an in vitro model of carcinogen-induced transformation
      consisting of 2 human uroepithelial cell lines immortalized by infection with SV
      40 was studied. One line, HUC-PC, is tumorigenic in nude mice after incubation
      with the carcinogen 4-ABP, the other, HUC-BC, is not. Cytoplasmic and nuclear F-
      and G-actin were determined by QFIA on individual cells using fluorochrome
      labeled phallicidin and DNase, I, respectively. Before exposure to 4-ABP, the PC
      cells had lower cytoplasmic F-actin content, higher cytoplasmic G-actin content,
      but similar levels of nuclear G- and F-actin in comparison to the BC cells. After
      incubation with 4-ABP, F-actin decreased and G-actin increased in both cytoplasm
      and nuclei of PC cells and cytoplasmic F-actin fibers were lost, but only
      cytoplasmic actin was altered in the BC cells. Northern blot analysis showed the
      expression of the beta-actin gene was only approximately 20% lower in 4-ABP
      treated PC cells than in untreated controls, indicating the cellular change in
      actin was attributed to a shift between F- and G-actin proteins rather than to
      net actin synthesis.

PMID- 9033651
TI  - Pleiotropic over-expression of multidrug-resistance-related genes is correlated
      to MYCN and max mRNA accumulation during tumour progression in the IGR-N-91 human
      neuroblastoma model.
AB  - An experimental model of advanced human neuroblastoma, IGR-N-91, which is able to
      disseminate in the nude mouse, has been described. The present study was designed
      to ascertain which cell population from the IGR-N-91 primary tumour actually
      disseminates throughout the animals. In s.c. IGR-N-91 tumour xenografts, 3 areas,
      called pearly, vascularized and haemorrhagic, depending on the presence of blood
      vessels and haemorrhagic suffusions, were consistently observed and independently
      resected. Molecular analysis of tumour materials revealed a significant increase
      in MYCN and max gene transcript levels in the haemorrhagic area, as compared with
      the pearly and vascularized areas. Given the growth kinetics observed both in
      vitro and in vivo, and the DNA flow-cytometry profiles of tumour cells obtained
      from the haemorrhagic area, this transcriptional increase did not appear to be
      associated with enhanced proliferation. In this area of the tumours, multidrug
      resistance-related genes, i.e., MDRI, MRP, GST-pi and topoisomerase II alpha were
      activated concomitantly with MYCN and max genes. The same observations were made,
      except for the topoisomerase-II alpha gene, when sub-lines derived from
      metastases were compared with that derived from the primary tumour. These data
      demonstrate that over-expression of several genes determining the multi-drug
      resistance phenotype precedes the metastatic spread of IGR-N-91 NB tumour cells
      in the nude mouse. Data also suggest that the cell sub-population exhibiting this
      pleiotropic over-expression within the primary tumour undergoes selection during
      metastatic dissemination.

PMID- 9033652
TI  - Multiple types of aberrations in the p16 (INK4a) and the p15(INK4b) genes in 30
      esophageal squamous-cell-carcinoma cell lines.
AB  - To determine the role and mode of inactivation of the p16 and p15 genes in human
      esophageal tumors, we examined alterations and expression of the alpha and beta
      forms of the p16 gene, 5' CpG island methylation of p16 exon 1 alpha, and
      alterations of the p15 gene in 30 esophageal squamous-cell-carcinoma cell lines.
      Of 30 such cell lines examined, 28 (93%) showed aberrations of the alpha form of
      the p16 gene: 18 homozygous deletions, 6 point mutations and 4 hypermethylation.
      Methylation was exclusively observed in cell lines with the wild-type alpha form.
      Of the 6 point mutations, one was observed in exon 1 alpha, one in the splice
      acceptor site of intron 1 and the remaining 4 were in exon 2. In the beta form,
      18 homozygous deletions and 3 point mutations in exon 2 were detected, but no
      point mutation was found in exon 1 beta. All mutations in exon 2 gave rise to
      premature termination codons in the reading frame of the alpha transcript, while
      no non-sense mutations were observed in the reading frame of the beta transcript.
      Among 12 cell lines without homozygous deletions of the alpha and beta forms of
      the p16 gene, the expected wild-type beta transcript was observed in 8 cell
      lines, whereas only one cell line expressed the expected wild-type alpha
      transcript. Homozygous deletions of the p15 gene were observed in 16 cell lines
      (53%), and no point mutations were detected. Twelve cell lines had alterations
      only in the alpha form of the p16 gene, while none showed aberrations exclusively
      in the p15 gene. Taken together, these results indicate that inactivation of the
      beta form of the p16 gene and the p15 gene are not so frequent as that of the
      alpha form of the p16 gene in ESC cell lines, suggesting that aberration of the
      alpha form of p16 gene is the primary target of 9p loss in ESC.

PMID- 9033653
TI  - Establishment and characterization of human gastric carcinoma cell lines.
AB  - We report 8 newly established gastric-carcinoma cell lines (SNU-216, 484, 520,
      601, 620, 638, 668, 719) from Korean patients. Morphologic study was carried out
      using light and electron microscopes. CEA, alpha FP, and CA 19-9 and TPA in
      supernatant and in cell lysate were measured by radioimmunoassay. p53 and c-Ki
      ras gene mutations were screened and confirmed by sequencing. The cell lines,
      derived from tumors with moderate differentiation, grew as a diffuse monolayer,
      and those from tumors with poor differentiation and minimal desmoplasia grew
      exclusively as non-adherent. Out of the 8 gastric-cancer cell lines, 5 had
      detectable levels of CEA both in supernatant and in cell lysate; there was no
      expression or secretion of alpha FP in these cells; 4 cell lines showed high
      levels of CA 19-9 in cell pellets. All cell lines except SNU-484 had high
      concentrations of TPA both in cell lysate and in supernatants. p53 mutation was
      found in 6 cell lines (75%): 2 (SNU-216 and SNU-668) had mutations in exon 6, and
      other 3 in exon 8. The c-Ki-ras mutation was found in 2 cell lines (25%), SNU-601
      and SNU-668. The former showed GGT-to-GAT transition mutation at codon 12, while
      the latter showed CAA-to-AAA transversion mutation at codon 61. DNA profiles
      using restriction endonuclease HinfI and polymorphic DNA probes ChdTC-15 and
      ChdTC-114 showed different unique patterns; which suggests that these cell lines
      are unique and not cross-contaminated. We believe that the newly characterized
      gastric-cancer cell lines presented in this paper will provide a useful in vitro
      model for studies related to human gastric cancer.

PMID- 9033654
TI  - Natural cell-mediated cytotoxicity (NCMC) against NK-sensitive tumours in vitro
      by murine spleen Ly-6C+ natural T cells.
AB  - Ly-6C+ cells constitute 13 +/- 3% of freshly isolated (CBA x C57BL/6)F1 mouse
      spleen leukocytes. Three distinct populations were identified: CD3 epsilon +NK
      1.1- conventional T cells (6%), CD3 epsilon -NK-1.1- granulocytes (5%) and CD3
      epsilon +NK-1.1+ T cells (approximately 2%). The CD3 epsilon +NK-1.1+ cells
      displayed a predominantly large granular leukocyte morphology and were the only
      Ly-6C+ cell subset identified by MAb 2B6-F2 to spontaneously lyse the NK
      sensitive YAC-1 tumour in vitro. On further phenotypic analysis, these cells co
      expressed high levels of TCRV beta 8.1/8.2 and CD11b, moderate levels of CD90 and
      low levels of CD4 or CD8. The removal of CD4+ and CD8+ cells prior to Ly-6C+ cell
      sorting showed that it was the CD4-CD8- double-negative (DN) CD3 epsilon +NK-1.1+
      T-cell subset which was responsible for killing YAC-1. These results indicate
      that we have identified a DN Ly-6C+ subset of the recently designated NK-1.1+TCR
      alpha beta low natural T (NT) cells, which are capable of natural cell-mediated
      cytotoxicity (NCMC) against the NK-sensitive YAC-I tumour in vitro. Additionally,
      these cells mediated the in vitro killing of 2 further NK-sensitive tumours,
      murine B16 melanoma and human Jurkat T lymphoma. YAC-1 and Jurkat expressed Fas
      and were susceptible to anti-Fas MAb or rhuman Fas ligand (rhFasL)-induced lysis.
      Furthermore, anti-human Fas MAb M3 was shown to block sorted Ly-6C+ splenocyte in
      vitro killing of Jurkat. In contrast, B16 did not express cell-surface Fas and
      was resistant to anti-Fas MAb-induced lysis. Taken together, these results show
      that not only do Ly-6C+ NT cells kill NK-sensitive tumours in vitro but they
      mediate this activity via multiple cytotoxic mechanisms including Fas.

PMID- 9033655
TI  - Plasminogen activators play an essential role in extracellular-matrix invasion by
      lymphoblastic T cells.
AB  - Involvement of extravascular sites, in particular infiltration of the central
      nervous system, is a frequent complication of T-lymphoblastic leukemia and
      contributes to leukemia-associated morbidity. In this report, we studied the
      contribution of plasminogen activators to the invasive properties of 7 human T
      cell lines in a model of transmigration through an extracellular matrix. The T
      cell lines were found to express either urokinase (u-PA) and high levels of u-PA
      receptor or tissue-type plasminogen activator (t-PA) and low levels of u-PA
      receptor. The rate of transmigration was consistently higher for u-PA-expressing
      cells than for t-PA-expressing cells. PA-inhibitor type 1 (PAI-1) was detected in
      the conditioned medium of one cell line and PAI-2 was detected in cell extracts
      from 6 lines. The transmigration of 6 out of 7 cell lines was inhibited by
      trasylol, an inhibitor of plasmin, by an excess of exogenous PAI-1 or PAI-2, and
      by antibodies to the particular PA type expressed by the cells. Partial
      inhibition of transmigration by the amino-terminal fragment of u-PA implies that
      the u-PA receptor contributes to transmigration. Thus, the transmigration of T
      leukemia cells through a barrier of extracellular matrix requires PA-dependent
      proteolysis, which can be provided either by u-PA or t-PA. Specific inhibition of
      the PA system could provide a means to inhibit tissue invasion by T lymphoblastic
      cells.

PMID- 9033656
TI  - Moving promising research findings to the clinic: methodological issues in the
      design and conduct of clinical trials of retinoids.

PMID- 9033657
TI  - Links between pharmacological properties of retinoids and nuclear retinoid
      receptors.

PMID- 9033658
TI  - Genetics of APL and the molecular basis of retinoic acid treatment.

PMID- 9033659
TI  - 13-cis retinoic acid and interferon-alpha +/- irradiation in the treatment of
      squamous-cell carcinomas.

PMID- 9033660
TI  - Expression of cytoplasmic retinoic acid-binding proteins and nuclear receptors in
      squamous-cell carcinomas in vitro.

PMID- 9033661
TI  - Retinoid-interferon therapy of solid tumors.

PMID- 9033663
TI  - All-trans-retinoic acid modulates the radiosensitivity of proliferating cells.

PMID- 9033662
TI  - Rapid induction of apoptosis in human C33A cervical carcinoma cells by the
      synthetic retinoid 6-[3-(1-adamantyl)hydroxyphenyl]-2-naphtalene carboxylic acid
      (CD437).

PMID- 9033664
TI  - Combination of alpha-interferon 2a (alpha-IFN 2a) and 13-cis-retinoic acid
      (13cRA) in recurrent, pre-treated squamous-cell carcinoma of head and neck
      (SCCHN).

PMID- 9033665
TI  - Differences in the pharmacokinetics of 13-cis retinoic acid in cancer patients.

PMID- 9033666
TI  - Clinical and molecular aspects of retinoid therapy for acute promyelocytic
      leukemia.
AB  - As a single agent, all-trans RA produces a higher rate of complete remission in
      APL than any other drug in any other neoplastic disease. The molecular findings
      in this illness have been exploited to develop a means of detecting and
      eradicating minimal residual disease. Compared with other forms of acute myeloid
      leukemia, this subtype is now associated with the highest proportion of patients
      in extended disease-free first remission who are presumably cured of their
      disease. APL is a prototype for understanding the pathogenesis of a malignant
      disease and the development of novel therapies that are targeted to specific
      molecular abnormalities.

PMID- 9033667
TI  - Carbon tetrachloride: genetic effects and other modes of action.

PMID- 9033670
TI  - 20 year cumulative index. Volumes 1-20, 1972-1992.

PMID- 9033669
TI  - 3rd International Congress on Drug Therapy in HIV Infection. Birmingham, United
      Kingdom, 3-7 November 1996. Abstracts.

PMID- 9033668
TI  - DNA adducts and chronic degenerative disease. Pathogenetic relevance and
      implications in preventive medicine.
AB  - Chronic degenerative diseases are the leading causes of death in developed
      countries. Their control is exceedingly difficult due to their multiplicity and
      diversity, the interconnection with a network of multiple risk factors and
      protective factors, the long latency and multistep pathogenesis, and the
      multifocal localization. Adducts to nuclear DNA are biomarkers evaluating the
      biologically effective dose, reflecting an enhanced risk of developing a mutation
      related disease more realistically than the external exposure dose. The
      localization and accumulation of these promutagenic lesions in different organs
      are the composite result of several factors, including (a) toxicokinetics (first
      pass effect); (b) local and distant metabolism; (c) efficiency and fidelity of
      DNA repair; and (d) cell proliferation rate. The last factor will affect not only
      the dilution of DNA adducts but also the possible evolution towards either
      destructive processes, such as emphysema or cardiomyopathies, or proliferative
      processes, such as benign or malignant tumors at various sites. They also include
      heart tumors affecting fetal myocytes after transplacental exposure to DNA
      binding agents, blood vessel tumors, and atherosclerotic plaques. In this
      article, particular emphasis is given to molecular alterations in the heart,
      which is the preferential target for the formation of DNA adducts in smokers, and
      in human aorta, where an extensive molecular epidemiology project is documenting
      the systematic presence of adducts to the nuclear DNA of smooth muscle cells from
      atherosclerotic lesions, and their significant correlation with known atherogenic
      risk factors. Exocyclic DNA adducts resulting from lipid peroxidation, and age
      related indigenous adducts (I-compounds) may also originate from endogenous
      sources, chronic infections and infestations, and inflammatory processes. Type II
      I-compounds are bulky DNA lesions resulting from oxidative stress, whereas type
      II-compounds are presumably normal DNA modifications, which display positive
      correlations with median life span and are decreased in cancer and other
      pathological conditions. Profiles of type II-compounds strongly depend on diet
      and are related to the antidegenerative effects of caloric/ dietary restriction.
      Even broader is the possible meaning of adducts to mitochondrial DNA, which have
      been detected in rodents exposed to genotoxic agents and complex mixtures, as
      well as in untreated rodents, in larger amounts when compared to the nuclear DNA
      of the same cells. Mutations in mitochondrial DNA increase the number of
      oxidative phosphorylation-defective cells, especially in energy-requiring
      postmitotic tissues such as brain, heart and skeletal muscle, thereby playing an
      important role in aging and a variety of chronic degenerative diseases. A
      decreased formation of DNA adducts is an indicator of reduced risk of developing
      the associated disease. Therefore, these molecular dosimeters can be used as
      biomarkers in the prevention of chronic degenerative diseases, pursued either by
      avoiding exposure to adduct-forming agents or by using chemopreventive agents.
      Interventions addressed to the human organism by means of dietary measures or
      pharmacological agents have encountered a broad consensus in the area of
      cardiovascular diseases, and are deserving a growing interest also in cancer
      prevention. The efficacy of chemopreventive agents can be assessed by evaluating
      inhibition of nuclear DNA or mitochondrial DNA adduct formation in vitro, in
      animal models, and in phase II clinical trials in high-risk individuals.

PMID- 9033671
TI  - Proceeding of the 25th International Conference on Animal Genetics. Tours,
      France, 21-25 July 1996. Abstracts.

PMID- 9033672
TI  - 2nd Congress of the Immunology of Diabetes Society. Canberra, Australia, December
      8-11, 1996. Abstracts.

PMID- 9033673
TI  - Directory issue of the Aerospace Medical Association.

PMID- 9033674
TI  - 22nd annual meeting of the American Society of Andrology. Baltimore, Maryland,
      February 22-25, 1997. Abstracts.

PMID- 9033675
TI  - 6th International Congress on Cell Biology and 36th American Society for Cell
      Biology annual meeting. San Francisco, California, December 7-11, 1996.
      Abstracts.

PMID- 9033676
TI  - [Results of treatment of hemifacial spasm by surgical and endoscopic
      neurovascular decompression. Analysis of 60 records].
AB  - The notion of a neurovascular conflict in the pathogenesis of hemifacial spasm is
      now well accepted based on evidence obtained from pre-operative imaging and per
      operative videoendoscopy of the pontocerebellous angle. We operated 60 patients,
      47 women and 13 men, age range 28-79 years, who had hemifacial spasms for 2
      months to 30 years. Neurovascular decompression of the facial nerve via the
      retrosigmoid access was performed using a minimal invasive technique: limited
      access of short duration, microsurgery, endoscopic and electrophysiologic
      techniques, positioning of Teflon microsponges between the nerve and the vessels
      involved. Surgery led to 90% good long-term results with minimal morbidity
      limited to auditive sequellae in 3.3% of the cases. The site of compression was
      at the point where the facial nerve emerged in 95% of the cases. Arteries
      involved were the posteroinferior cerebellous artery (39 cases), the vertebral
      artery (23 cases) and the anteroinferior cerebellous artery (16 cases). In a
      third of the cases, the vascular conflict involved more than one vessel. The
      facial nerve should be isolated from any nociceptive contact to obtain definitive
      cure.

PMID- 9033677
TI  - [Sensory afferences and motor control of equilibrium using static and dynamic
      posture tests].
AB  - One thousand two hundred posturographic tests have been performed since 1988 at
      the Laboratoire d'Exploration Fonctionnelle ORL, Centre Hospitalier
      Universitaire, Nancy-Brabois, using three complementary protocols (Toennis GmBh,
      G). Static tests [1] measure over 20 seconds periods the displacement of the
      center of foot pressure (CFP) on individual standing upright on the platform.
      Dynamic tests assess the mechanisms of balance control following measured
      platform movements, using surface EMG after a single sharp and unexpected tilt
      [2], or CFP displacements during longer regular oscillations of the platform [3].
      The latter test enables an analysis of balance strategy adopted to maintain
      equilibrium. These three programs were applied to series of children, adults,
      elderly people, sportsmen, and patients suffering from ENT, neurological or
      traumatic disorders. They were confirmed to be complementary tests allowing a
      thorough investigation of all balance control mechanisms: visual afferences [1],
      somesthesy [2] and the combination of visual, somesthetic and vestibular
      afferences in the third test.

PMID- 9033678
TI  - [Electrophysiologic and other objective tests in pediatric cochlear
      implantation].
AB  - Various electrophysiological procedures have been developed and utilized in
      pediatric cochlear implant patients. During surgery and just before implantation,
      recording of Electrically-Evoked Auditory Brainstem Responses (EABR) by
      electrical stimulation via a promontory needle electrode is a useful tool to
      select the suitable ear for implantation in the absence of other criteria. After
      implantation, peroperative assessment of the Electrically-Evoked Stapedius Reflex
      thresholds allows an estimation of the comfort levels not to be exceeded during
      the first tuning sessions. Recording of Averaged Electrode Voltages (AEV)
      provides assurance against general device failure, and can localize defectives
      electrodes which will be disactivated. Finally EABR obtained by electrical
      stimulation via the implant is the last control showing objective auditory
      responses. Furthermore there is a strong correlation between EABR thresholds and
      behavioral thresholds which will be obtained during the first tuning session.
      When a device malfunction is suspected after implantation, recording of AEV and
      EABR are performed, and the results are compared with the preoperative data.

PMID- 9033679
TI  - [Photochemotherapy in the treatment of carcinoma of the vocal cords of early
      stage (Tis, T1)].
AB  - Photodynamic Therapy (PDT) is a treatment which can prove interesting in head and
      neck oncology for small squamous cell carcinomas. We studied 33 patients with
      vocal cord squamous cell carcinoma at an early stage who have been treated by
      Photodynamic Therapy from 1986 to 1992. We used a Dye Laser Aurora which produces
      light with a wavelength of 630 nm. The intervention was done under general
      anesthesia, 72 hours after the injection of hematoporphyrin derivative. The mean
      and the maximum follow-up was respectively 66 and 93 months. The local control
      after an exclusive PDT was 73% at 3 years, 5 years, 7 years. If this method
      fails, a conventional treatment may be used.

PMID- 9033680
TI  - [Surgery of primary malignant melanomas of the mucosa of the nasal fossa and
      facial sinuses].
AB  - A retrospective analysis of 22 patients with primary malignant melanoma of the
      nasal fossa and/or paranasal sinuses consecutively managed with surgery at our
      department from 1975 to 1993 was conducted. Fifteen patients had negative margins
      of resection. Neoadjuvant chemotherapy and post-operative radiation therapy was
      associated in 4 and 5 of these 15 patients, respectively. Four patients had
      positive margins. Adjunctive treatment was chemotherapy and postoperative
      radiation therapy in 2 and 3 of these 4 patients, respectively. The remaining 3
      patients were managed with palliative treatment (debulking surgery and
      chemotherapy). No patients were lost to follow up. A 3-year follow-up was always
      achieved. In patients in whom surgical resection achieved negative margins, the 5
      year actuarial survival, and local control estimate was 17.9%, and 26.9%,
      respectively. None of the variables under analysis were statistically related to
      local recurrence or survival. Death always occurred within 24 months from initial
      diagnosis in all 7 patients but one in whom surgical resection with negative
      margins was not achieved or debulking surgery was performed.

PMID- 9033681
TI  - [Percutaneous gastrostomy in interventional radiology in cervico-facial oncology.
      Apropos of 174 cases].
AB  - We report a series of 174 percutaneous gastrostomies implanted in our
      interventional radiology unit in patients with cancer of the upper airway and
      upper digestive tract: two localizations, hypopharynx and oropharynx comprised
      68% of the cases (106/174). Tumor stage had reached palliative treatment in 80
      cases, was in the initial phase of treatment in 57 cases and was in a sequelae
      phase after treatment in 37 cases. Despite problems related to anatomic
      modifications and tumor volume or sequelae of prior or ongoing treatment, we did
      not record any failures. The rate of minor complications was 15%. The one severe
      complication (peritonitis) required laparotomy. The duration of enteral nutrition
      via the gastrostomy varied from 3 weeks to more than 3 years. There were no long
      term complications. We thus suggest that interventional percutaneous gastrostomy
      is a useful alternative to endoscopic percutaneous gastrostomy or the
      nasoesophageal tube, particularly in patients with voluminous tumors restricting
      the hypopharynx and oropharynx.

PMID- 9033682
TI  - [Chronic tinnitus and hearing loss caused by cerebrospinal fluid leak treated
      with success with peridural blood patch. Apropos of 2 cases].
AB  - Hearing loss and tinnitus are frequently encountered in ENT patients and usually
      require complementary investigations such as audiogram, auditive evoked
      potentials, CT scan, MRI... One recent etiology, that is more and more
      discovered, is a decrease in spinal fluid pressure secondary to a dural fluid
      leak that occurs after a diagnostic lumbar puncture, a spinal anesthesia, an
      accidental dural puncture during an epidural technique or a lumbar myelography.
      Postural headache which are frequently present in such a setting, may mask these
      auditive symptoms. Epidural injection of autologous blood (blood patch) performed
      by anesthesiologists, which is usually indicated to treat such postural
      headaches, is efficient in relieving other symptoms related to spinal fluid leak
      after dural puncture. We report two cases of isolated auditive complaints
      (hearing loss and tinnitus) which have been dramatically improved after blood
      patch. In conclusion, ENT surgeons should seek for a recent or even a past
      history of spinal puncture whenever the etiology of auditive symptoms of their
      patient remains unclear.

PMID- 9033683
TI  - [Sinus mucoceles. Apropos of 5 cases].
AB  - Our retrospective study of 5 cases of sinus mucocele confirmed its rarity and
      occurrence at any age. This uncommon disease might be due to an association of
      inflammation, ostium closure and hypersecretion. The volume of the fronto
      ethmoidal mucocele let us operate on patients either by orbito-superciliary route
      or through the frontal scalp. Functional endoscopic surgery, presently suggested
      for mucocele treatment, was not used because of our lack of experience in this
      surgical method.

PMID- 9033684
TI  - [Surgical treatment under endoscopic control of cerebrospinal fluid rhinorrhea of
      sphenoid origin. A propos of 5 cases].
AB  - From 5 to 15% of cerebrospinal fluid (CSF) leaks come from the sphenoid,
      subdivided in two groups: traumatic and spontaneous. Many surgical approaches are
      used for their treatment, with consistent morbidity. Five sphenoidal CSF leaks (3
      traumatic and 2 spontaneous) were operated only by endoscopic endonasal route
      from 1993 to 1995, after endoscopic and computerized tomography (CT) scan
      evaluation. A sphenoidotomy by a simple endonasal route through the spheno
      ethmoidal recess was performed in 3 cases. In the other 2 cases, the
      sphenoidotomy required a trans-ethmoidal approach through the posterior part of
      the ethmoid. After identification of the leak and the removal of mucosa, the
      sphenoid sinus was filled up by abdominal fat kept in place by biological glue
      and supported by a silastic sheat. No post-operative complication appeared. The
      median duration of hospitalization was 6.5 days (5-13). During the follow-up
      (19.5 months, 8-30), 4/5 complete remission was observed. The last case needed a
      second obturation at 11 months, due to a retraction of the fat, without
      recurrence. This endonasal endoscopic approach is safe and efficient for leaks
      closure, with no morbidity compared with others invasive approaches.

PMID- 9033685
TI  - [Osteoma of the naso-sinusal cavities. Surgical indications and role of endonasal
      endoscopic surgery].
AB  - Osteoma of the para-nasal sinuses is a rare and benign tumor that develops
      slowly. When therapy becomes mandatory, it is necessarily surgical and requires a
      standard external approach. This report analyses seven cases of operated
      osteomas, using different surgical techniques, adapted to different indications.
      Three patients underwent exclusive endonasal endoscopic surgery, and four
      patients had external surgery coupled with endonasal surgery. Results have proven
      successful with a four-year median follow-up. Epidemiological, clinical,
      histological and therapeutic considerations as well as the value of the
      endoscopic endonasal surgical approach are discussed. Endonasal endoscopic
      surgery can be used alone in naso-ethmoidal osteomas. It must, though, be
      associated with external standard procedure when the osteoma involves important
      extension to the frontal sinuses. In isolated frontal osteomas, external standard
      approach is mandatory for resection, endonasal technique being in this case
      contributive to the repermeabilisation of the infundibulum.

PMID- 9033686
TI  - [Horizontal supraglottic laryngectomy. Technique, indications, oncologic results
      and early functional results. Apropos of 87 cases].
AB  - In this article, we advocate supraglottic laryngectomy with bilateral neck
      dissection for the treatment of supraglottic carcinomas with preserved laryngeal
      mobility. Post-operative results and follow-up of 87 patients are discussed. This
      technique allows an excellent loco-regional control of the disease with
      preservation of laryngeal function. Radiation therapy is preserved for treatment
      of metachronous (2nd primary) in cases with satisfactory local control without
      neck metastases. All stage 5-year overall survival rate was 55% with a 68.5%
      disease survival rate. Five-year local control of the disease and regional
      control of neck nodes were respectively 94% and 92%. Five-year disease survival
      rate for N- population was 71% Vs 61% for N+ population. Five-year disease
      survival rate according to the tumor classification was 70% for T1, 75% for T2,
      69% for T3 and 54% for T4. In the post-operative follow-up, the median of time to
      decanulation was 17 days, that of nasogastric tube removal was 19 days, that of
      hospital stay 38 days.

PMID- 9033687
TI  - [Metastatic cervical adenopathies of unknown primary site. Long-term course].
AB  - We conducted a retrospective study of 34 patients treated by radical neck
      dissection followed by radiotherapy for one or several cervical adenopathies
      without a primary tumor. Mean follow-up was 48 months. During follow-up, 6
      patients developed a presumed primary tumor, and 11 patients presented with
      recurrent lymph nodes. We found no statistically significant predictive factor,
      as to either clinical characteristics or the histological nature of the
      adenopathies. On the other hand, the number of metastatic lymph nodes found on
      the surgical specimen was correlated with the risk of lymph node recurrence.
      Among the prognostic factors with an unfavorable effect on survival, the
      dimensions of the adenopathy, its fixed characteristic and its TNM status, were
      identified. In this series, the appearance of a primary tumor did not seem to
      worsen the prognosis. On the other hand, the appearance of lymph node recurrence
      predicted poorer survival rates. The results are discussed and compared with
      those found in the literature.

PMID- 9033688
TI  - [Extemporaneous anatomo-pathological test in surgery of thyroid cancers. Values
      and limitations].
AB  - We report our experience in surgical treatment of thyroid cancer; 2470 total or
      partial thyroidectomies were performed for a thyroid nodule, 205 were primitive
      thyroid carcinoma (8.3%). Intraoperative frozen sections diagnoses were performed
      in 100% of the patients. In this study, a 100% specificity and 74% sensitivity
      were found. Data for each histological type were compared with the previous
      studies. Each false negative macroscopic aspect carcinoma's size,
      differenciation, plurificality were studied in order to understand the limits of
      frozen sections diagnoses. The higher rate of false negative was found with
      small, well differenciated vesicular carcinoma. This study shows that high
      accuracy of frozen sections diagnoses allows to improve the intraoperative
      management of thyroid cancer. The high specificity of frozen sections diagnoses
      strengthens our reliance upon this examination.

PMID- 9033689
TI  - [Indications and complications of free micro-flaps in ORL oncology].
AB  - Eighty-three free flaps were used to repair head and neck cancer defects between
      1993 and 1995. The flaps used were 37 (44%) radial forearm flaps, 29 (35%) iliac
      crest flaps, 8 (10%) free jejunum flaps, 4 (5%) fibula flaps, 3 (3%) latissimus
      dorsi flaps and 2 (2%) rectus abdomini flaps. The indications for each flap are
      discussed. The flap loss rate was 4.8%, which led to reoperation with a new free
      flap in 3.6% of the cases. The other complications are discussed. Pre and post
      operative radiotherapy had no influence on the outcome of the free flaps. The
      mean duration of hospitalisation was 36 days. 78% of the patients who underwent a
      mandibular reconstruction were fitted with a fixed dental prosthesis and had
      normal mastication. 66% of the patients with oropharyngeal reconstruction had
      normal deglutition and 30% had a mixed diet. The acceptable complication rate,
      the good esthetic and functional results obtained with free flaps indicate that
      they should be used as a first choice technique in the reconstruction of head and
      neck cancer defects.

PMID- 9033691
TI  - [How to attach an aponeurosis flap in myringoplasty. Value of the buttonhole
      technique].

PMID- 9033690
TI  - [A case of Kikuchi disease. Review of the literature].
AB  - We report a case of Kikuchi's disease in a young man. It is a rare entity,
      described for the first time in 1972. It manifests clinically with cervical
      adenopathy and fever, often associated with other non-specific clinical signs.
      Laboratory tests are often normal. The diagnosis is established on the basis of
      histologic of lymph node excisional biopsy. Kikuchi's disease is likely to be
      misinterpreted as malignant lymphoma or systemic lupus erythematosus. It
      generally needs no treatment because it runs a spontaneously benign course with
      complete resolution of the symptoms within 6 months. Secondary systemic lupus
      erythematosus may develop. For this reason, regular follow-up of patients is
      recommended. The etiopathogenesis of this disease is still unknown, perhaps due
      to an immunologic phenomenon. It could be a hyperimmune reaction induced by
      various antigenic agents (infectious, neoplasic), or an autoimmune process.

PMID- 9033692
TI  - [Ventricular late potentials and sleep apnea syndromes].
AB  - This prospective study in 37 patients evaluated the prevalence of ventricular
      late potentials in sleep apnea syndrome, a condition associated with an increased
      risk of ventricular rhythm disorders and sudden death. A comparative analysis was
      conducted among a group of patients considered free of coronary heart disease and
      admitted for suspected sleep apnea syndrome based on clinical symptoms and simple
      blood gas measurements. The prevalence of ventricular late potentials was 56% in
      the subgroup with and 14% in the subgroup without polygraphy evidence of apnea (F
      < 0.01). The analysis of clinical, respiratory, and echocardiographic findings in
      the apneic subgroup failed to detect any factors associated with the presence of
      ventricular late potentials. Only long-term follow-up studies involving invasive
      heart rhythm testing could define the prognostic significance of ventricular late
      potentials in sleep apnea syndrome. However, our data demonstrate that there is
      an association between ventricular late potentials and sleep apnea syndrome.

PMID- 9033693
TI  - [Left ventricular hypertrophy in patients with hypertension. A comparative study
      between black Africans and white Europeans].
AB  - OBJECTIVE: The objective of this study was to compare clinical and
      ultrasonographic findings in 20 consecutive hypertensive Black Africans, with
      those of 20 hypertensive White Europeans matched for age in order to study
      modifications of left ventricular (VG) geometry. METHOD: 20 consecutive Black men
      (B), recently emigrated from Africa and applying for asylum, referred for HT,
      were assessed by measuring systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and pulse pressure (PP), body mass index (BMI), echocardiography
      with measurement of the end-diastolic thickness of the septum, posterior wall
      (Epp), LV diameter (DTD), calculation of the LV mass index (LVMI) according to
      the Penn convention and the thickness/radius ratio (t/r). These subjects were
      matched for age with 20 consecutive European White men (W) sent to the
      echocardiography laboratory for assessment of HT, in whom the same parameters
      were measured. RESULTS: The mean age was 41.6 +/- 9.2 (B) vs 42.1 +/- 8.8 years
      (W) (NS). The BMI was 26.3 +/- 3.2 (B) vs 27.3 +/- 3.4 (W) (NS). SBP was 175 +/-
      24 (B) vs 156 +/- 15 mmHg (W) (p < 0.01). DBP was 108 +/- 13 (B) vs 94 +/- 9 mmHg
      (W) (p < 0.01). PP was 67 +/- 20 (B) vs 63 +/- 10 mmHg (W) (NS). LVMI was 131 +/-
      43 (B) vs 91 +/- 19 g/m2 (W) (p = 0.001). The t/r ratio was 0.48 +/- 0.08 (B) vs
      0.38 +/- 0.07 (W) (p < 0.001). DTD was 47.1 +/- 3.9 (B) vs 48.6 +/- 4.4 mm (W)
      (NS). Epp was 11.2 +/- 1.9 (B) vs 9.1 +/- 1.4 mm (W) (p < 0.001). A poor
      correlation was observed between SBP and LVMI (r = 0.23, p = 0.17), and between
      SBP and t/r (r = 0.21, p = 0.21). CONCLUSION: Compared to a age-matched
      population of European hypertensive patients with similar morphology, our
      homogeneous group of recently emigrated patients was characterized by a greater
      severity of HT and the presence of concentric left ventricular hypertrophy. The
      marked difference in socio-economic status and access to care of these two
      populations must be stressed.

PMID- 9033694
TI  - [Predictive factors of thromboembolic complications in mitral stenosis in sinus
      rythm].
AB  - The authors analyse the predisposing factors to the development of thromboembolic
      complications in mitral stenosis in sinus rhythm and propose preventive
      therapeutic measures. Eighty five consecutive patients with pure or very
      predominant mitral stenosis in sinus rhythm were included in this study and
      divided into two groups according to the presence (Group I: n = 27, age: 34.2 +/-
      8.31 years) or absence (Group II: n = 58, age: 32.6 +/- 9.7 years) of
      thromboembolic complications. No significant difference was observed between the
      two groups for age, sex and functional class. Patients of group I had a more
      dilated left auricle (57.3 +/- 4.5 vs 48.4 +/- 4.7 mm; p < 0.001) and a smaller
      mitral surface area (0.8 +/- 0.15 vs 1.1 +/- 0.21 cm2, p < 0.05). The spontaneous
      left intra-atrial contrast phenomenon was more frequently observed in patients
      with thromboembolic complications (23 out of 27) than in those not presenting
      this complication (17 out of 58), (p < 0.001). This phenomenon was the only
      independent predictive factor on multivariate analysis. In conclusion, left
      atrial dilatation, the severity of mitral stenosis and especially the presence of
      spontaneous contrast are the main predictive factors of the development of
      thromboembolic complications in mitral stenosis in sinus rhythm. Patients
      presenting one or several of these factors may benefit from prophylactic
      anticoagulant treatment.

PMID- 9033695
TI  - [Fortuitous discovery of Brugada syndrome in an asymptomatic 70-year-old
      sportsman].
AB  - The authors report the case of an elderly sportsman presenting with the
      electrical signs of the syndrome described by Brugada. The absence of any serious
      clinical events in this patient questions the pejorative prognosis usually
      reported and the specific identity of this syndrome in relation to right
      ventricular arrhythmogenic dysplasia.

PMID- 9033696
TI  - [Myocardial infarction caused by thrombosis of the left coronary artery in a
      patient with thrombocythemia].
AB  - Myocardial infarction is not exceptional in patients with essential
      thrombocythaemia. This infarction is often related to the formation of in situ
      coronary thrombosis with no associated atheromatous lesions. The authors report
      the case of a thrombocythaemic patient with anterior infarction due to thrombosis
      of the left coronary artery. The clinical course is often more severe than in
      nonthrombocythaemic patients. The pathophysiological mechanisms remain unclear,
      but appear to be related to qualitative rather than quantitative platelet
      abnormalities.

PMID- 9033697
TI  - [Double recurrence of myxoma of the left atrium. Apropos of a case].
AB  - Multiple recurrences of cardiac myxomas are rare and high-light the problem of re
      operation. We report a case of double recurrence of left atrial myxoma and
      analyse the causes of recurrence. In our case, the first myxoma was inserted in
      the left inter-atrial septum, and the first recurrent tumor was inserted near the
      pulmonary vein, forming adhesion with the inter-atrial septum. The second
      recurrent tumor was inserted in the inter-atrial septum. The first operation
      resected the tumor, including part of the inter-atrial septum, and the sides of
      the septum were sutured. The two following operations used a patch for the
      septoplasty. This case is sporadic and not included in the high risk myxoma
      recurrence syndrome. Incomplete tumor resection is incriminated in one third of
      recurrences but seems unlikely in our case.

PMID- 9033698
TI  - [Diastolic dysfunction in chronic renal failure patients under hemodialysis].
AB  - Myocardial hypertrophy due to volume and pressure overload is common in
      hemodialysis patients because renal failure is usually responsible for arterial
      hypertension. The left ventricular filling pattern often exhibits abnormalities
      denoting a relaxation disorder. These abnormalities increase after hemodialysis
      sessions, which are sometimes followed by severe hypotension. This sequence of
      left ventricular hypertrophy, altered relaxation, and severe postdialysis
      hypotension sometimes associated with severe ventricular rhythm disorders
      deserves to be studied in detail. The data gathered would help to determine the
      prognosis in this situation, which often depends on cardiac function.

PMID- 9033699
TI  - [Effects of rilmenidine (hyperium) on lipid balance in hyperlipidemic
      hypertensive patients. Randomized, controlled, double-blind 8-week study vs.
      captopril in parallel groups].
AB  - Rilmenidine (dose of 1 mg once or twice a day) is the first oxazoline compound
      with antihypertensive properties. Its effects on lipid parameters [total
      cholesterol, HDL and LDL fractions, triglycerides, apolipoprotein A1 and B,
      lipoprotein (a)] were compared under double-blind conditions and in parallel
      groups to those of captopril (50 to 100 mg per day, in 2 divided doses) over a
      period of 8 weeks, in 51 hyperlipidaemic hypertensive patients [age: 56.3 +/- 1.5
      years, systolic and diastolic blood pressure (SBP/DBP): 165.1 +/- 2.0/99.1 +/-
      0.6 mmHg, LDL cholesterol: 5.38 +/- 0.16 mmol/L]. No significant difference was
      demonstrated between the groups on inclusion for any of the clinical parameters
      (SBP, DBP, heart rate (HR)) and laboratory parameters, apart from apolipoprotein
      A1, for which the mean value was higher in the rilmenidine group than in the
      captopril group (p < 0.05). No difference between the groups was demonstrated
      during the 8 weeks of treatment for the course of blood pressure: SBP and DBP
      decreased by 20.5 and 13.9 mmHg, respectively, in the rilmenidine group and by
      21.3 and 13.1 mmHg in the captopril group (no significant difference: NS). HR
      decreased by 0.3 beats per minute (bpm) in the rilmenidine group and by 4.1 bpm
      in the captopril group (NS). No statistically significant difference in lipid
      parameters was observed between the two groups. No clinically significant
      variation in any of the lipid parameters was observed after 8 weeks of treatment
      with rilmenidine or captopril. These results confirm the antihypertensive
      efficacy and neutrality of rilmenidine on lipid metabolism over a period of 8
      weeks. Rilmenidine therefore represents a useful alternative in the first-line
      treatment of hypertension in hyperlipidaemic hypertensive patients.

PMID- 9033700
TI  - [Diagnostic value of echocardiography under dobutamine in everyday practice].
AB  - In order to evaluate the place of dobutamine echocardiography in everyday
      practice, this test and a stress ECG were performed in 34 patients referred for
      diagnostic or assessment coronary angiography. Dobutamine, administered in 3
      minute stages from 5 to 30 micrograms/kg/min, was well tolerated. The anti
      ischaemic treatment was continued in 26 patients before dobutamine
      echocardiography and in 15 patients before the stress ECG. The
      electrocardiographic, echocardiographic and angiographic documents were each
      analysed by 2 independent observers. Dobutamine echocardiography was considered
      to be positive in the presence of the development of a new abnormality of
      segmental kinetics or when abnormality of segmental kinetics was identified
      outside of the territory of infarction. With reference to coronary angiography,
      the sensitivity of stress ECG and dobutamine echocardiography was 46% and 42%,
      respectively, and the specificity was 75% and 88%, respectively; the sensitivity
      of each test was low, probably because of fake tests. The combination of the two
      tests improved the sensitivity (69%) without altering the specificity (75%).
      Dobutamine echocardiography could usefully complete a negative stress ICG
      whenever a false-negative result is suspected to avoir wrongly reassuring some
      patients and to allow appropriate management.

PMID- 9033701
TI  - [Left ventricular distribution of retrograde cardioplegia. Should the
      interventricular posterior vein be occluded in the coronary sinus?].
AB  - Retrograde cardioplegia is still controversial due to the heterogeneous left
      ventricular flow distribution particularly in the posterior wall. The purpose of
      this study was to compare retrograde flow distribution delivered through the
      coronary sinus with two types of cannula. Fifty two patients were prospectively
      randomized to receive cold blood retrograde cardioplegia with manual inflating
      long balloon prototype cannula (group I, 26 patients) or with manual inflating
      short balloon cannula (group II, 26 patients). Left ventricular distribution of
      the cardioplegic solution was assessed by monitoring the left ventricular wall
      temperatures (anterior and posterior). The cardioplegic retrograde infusion was
      stopped as the anterior wall temperature reached 15 degrees C. In group I, 91% of
      the patients had identical cooling in the anterior and posterior wall of the left
      ventricle, versus 19% in group II (p < 0.05). The mean temperature difference
      between anterior and posterior wall was 0.5 degrees C (standard deviation = 1.7)
      in group I versus 8 degrees C (standard deviation = 4.1) in group II (alpha <
      0.05). The cannula with the long balloon allows a better left ventricular
      distribution of the cardioplegia flow than the short one because it occludes the
      interventricularis posterior vein in the coronary sinus.

PMID- 9033702
TI  - [Right retroauricular hematoma of late manifestation. Contribution of cardiac
      imaging].
AB  - Right intrapericardial retroatrial haematomas are usually discovered in an acute
      context of tamponade, following cardiac surgery. The original feature of this
      case was the asymptomatic nature of a right retroatrial haematoma, after surgical
      closure of an ostium secundum atrial septal defect, with a free interval of more
      than 20 years between the surgical procedure and the first relatively minor
      symptoms, consisting of supraventricular arrhythmias. It can be difficult to
      determine the intra- or extra-atrial topography of a right-sided mass by
      transthoracic echocardiography. On the other hand, transoesophageal
      echocardiography and ultrafast CT can provide a precise topographic diagnosis and
      appear to be complementary to assess the nature of pericardial masses.

PMID- 9033703
TI  - [Abnormal origin of the left coronary artery from the pulmonary artery.
      Diagnostic contribution of ultrasonographic technique].
AB  - We report a case of abnormal origin of the left coronary artery from the
      pulmonary artery trunk. The original features of this case were its discovery in
      a young pregnant woman, the normality of basal left ventricular function and the
      electrocardiogram, the diagnosis by transoesophaegeal echocardiography, and the
      demonstration of severe myocardial ischaemia by stress echocardiography.

PMID- 9033704
TI  - [Pleuropericarditis complicated of tamponade disclosing mixed connective tissue
      disease. Remission with non-steroidal anti-inflammatory agents. Apropos of a
      case].
AB  - Mixed connective tissue diseases or Sharp's syndrome are inflammatory diseases
      essentially presenting in the form of joint, muscle and skin manifestations.
      Pleuropericardial involvement is uncommon and rarely the presenting sign, and
      tamponade is exceptional. This clinical report concerns a case of
      pleuropericarditis complicated by tamponade in a 22-year-old man, constituting
      the presenting sign of Sharp's syndrome. The diagnosis of mixed connective tissue
      disease was based on the combination of clinical signs and a high serum anti-RNP
      antinuclear antibody titre. The treatment of the pericarditis is base on
      prescription of corticosteroids, but non-steroidal anti-inflammatory drugs were
      sufficient in our case. Larger effusions may require corticosteroids and
      pericardial drainage. We report the value of immunological assays in the
      aetiological assessment of pleuropericarditis in young subjects.

PMID- 9033705
TI  - [Ilio-femoral vein thrombosis treated with tissue plasminogen activator in a
      pregnant woman].
AB  - A 27-year-old woman, after 31 weeks of amenorrhoea during her second pregnancy,
      developed a left external iliac and femoral deep vein thrombosis, confirmed by
      venous ultrasonography and magnetic resonance imaging. The infusion of tissue
      plasminogen activator (rt-PA: 1.2 mg/kg, i.e. 80 mg over 3 hours), on the 2nd
      day, allowed revascularization of the femoral junction, while the external iliac
      vein remained occluded. The patient did not develop pulmonary embolism or
      haemorrhage, particularly obstetric haemorrhage. The subsequent pregnancy was
      uneventful until delivery, six weeks later, of a normal child. Three years later,
      the patient has no sequelae of her deep vein thrombosis. When required by the
      patient's condition, it seems that rt-PA can be used to treat severe deep vein
      thrombosis during pregnancy, either isolated or complicated by pulmonary
      embolism. Very rigorous cardiological, obstetric and laboratory surveillance is
      essential. A sufficient dosage, identical to that used in clinical settings other
      than pregnancy and a brief treatment duration (2 to 3 hours) are probably more
      effective and more reliable than lower doses continued for several days. However,
      the risk of haemorrhage remains difficult to predict and its prognosis,
      especially foetal, is often very poor. A larger series of cases is therefore
      necessary before this drug can unreservedly recommended in pregnant women.

PMID- 9033706
TI  - [Value of echocardiography-dobutamine in the study of reserve myocardial
      contractility in aortic stenosis with alteration of left ventricular function.
      Apropos of a case].
AB  - The authors report a case of tight aortic stenosis, without coronary artery
      disease, presenting with heart failure, alteration of global left ventricular
      contractility and a low gradient. Increasing-dose dobutamine echocardiography
      demonstrated an improvement of myocardial contractility and an accentuation of
      the transvalvular gradient. The place of this examination in the therapeutic
      strategy and follow-up of the disease is discussed in the light of the current
      data of the literature.

PMID- 9033707
TI  - [Transesophageal cardiac echography and paracardiac tumor masses. Apropos of a
      case].
AB  - Computed tomography is currently the reference examination in the investigation
      of mediastinal tumours. We report a case of pericardial tumour revealed by
      transoesophageal echocardiography. This investigation immediately defined the
      limits of this mass and its relations with cardiac cavities and large vessels and
      suggested the main features of its tissue structure. However, the aetiological
      diagnosis is still based on CT-guided needle biopsy or investigation by
      mediastinoscopy or thoracotomy. Our case consisted of a non-Hodgkin lymphoma.
      Transoesophageal echocardiography is a non-irradiating technique, which can be
      performed at the patient's bed and which allows a precise assessment of the
      pericardial regions, especially the right pericardial regions.

PMID- 9033708
TI  - [Patent foramen ovale, aneurysm of the interatrial septum and cerebral ischemic
      complication].
AB  - Persistence of a patent foramen ovale (PFO) and the presence of an aneurysm of
      the interatrial septum (AIAS) are significantly more frequent in patients
      examined for cerebral ischaemic accident of unknown cause than in control
      subjects. The mechanism of ischaemic accidents associated with these cardiac
      abnormalities (frequently associated with each other), particularly the frequency
      of paradoxical embolism, remains unclear. In young patients, the risk of
      recurrent cerebral ischaemic accident appears to be generally low (1 to 2% per
      year). Secondary prevention remains empirical and controversial. No comparative
      studies are available to demonstrate the superiority of platelet antiaggregants,
      oral anticoagulants or invasive treatments, such as endovascular or surgical
      closure of the foramen ovale. A rational treatment can only be proposed on the
      basis of a better understanding of the natural history of ischaemic recurrences
      (identification of subgroups of patients at high or low risk of recurrence) and
      the therapeutic benefit risk ratio.

PMID- 9033709
TI  - [Esophageal approach in rythmology. Diagnostic and therapeutic applications].
AB  - The oesophageal route is a simple technique, which is easy to perform. It allows
      precise assessment of supraventricular arrhythmias without using the endocavitary
      route. There is a perfect correlation between the two methods for the study of
      sinus function and the Wenckebach point. This technique makes a considerable
      contribution to the diagnosis of junctional tachycardia and the evaluation of
      Wolff-Parkinson-White syndrome. It can reduce approximately 65% of flutters and
      50% of atrial tachyarrythmias. It can also be used to monitor antiarrhythmic
      treatment or in the assessment of radiofrequency resection, especially in nodal
      tachycardias and left atrioventricular accessory pathways. Its limitations
      concern the sometimes painful nature of the investigation and the impossibility
      of recording the electrical activity of the His bundle.

PMID- 9033710
TI  - [So go allergens!].

PMID- 9033711
TI  - [Neuroendocrine primary cutaneous carcinoma. Therapeutic aspects in 13 patients].
AB  - INTRODUCTION: Since the description by Toker in 1972, neuroendocrine carcinoma or
      Merkel cell carcinoma, is a well identified clinical entity although the
      appropriate treatment is still debated. Wide surgical exeresis is indicated as
      first line treatment in all cases but the question concerning protocols for
      adjuvant radiotherapy or chemotherapy remains open. We analyzed retrospectively
      our series of 13 patients with neuroendocrine carcinoma looking for an
      association between radiotherapy and surgery. PATIENTS: There were 7 women and 6
      men in our study population (age range 43-88 years). Two cancers of the rectum
      and one prostate cancer were associated. In 6 cases, the tumor was localized on
      the limbs, in 5 on the face and in 2 on the buttocks. Mean delay to diagnosis was
      2.5 months. At diagnosis, only 1 patient had satellite nodes. The pathology
      examination evidenced intermediary cell type and architecture.
      Immunohistochemistry tests were positive for NSE, NF, KII and the ultrastructure
      confirmed the diagnosis. Nine patients were treated with surgical exeresis with
      wide 1 cm margins and was completed with radiotherapy of the tumoral bed at
      homogeneous doses of 45 to 60 Gy. Surgery alone was used in 4 patients. RESULTS:
      Mean follow-up was 27 months (5-98). Among the 13 operated patients, 11 have
      survived, 1 died due to the neoplasia and in 1 other from another cause. Local
      and regional recurrence rate after exercise alone was 50 p. 100 (2/4) with
      concomitant development of metastasis in both cases. When local or locoregional
      post-operative radiotherapy was given, local or regional recurrence rate was 33
      p. 100 (2/6). DISCUSSION: Cutaneous neuroendocrine carcinoma or Merkel cell
      carcinoma is an uncommon skin tumor. It is difficult to determine the management
      protocol on the basis of data in the literature. Due to risk of locoregional
      recurrence, we currently propose post-operative radiotherapy of the tumor bed and
      drainage nodes in all patients.

PMID- 9033714
TI  - [AIDS-related eosinophilic folliculitis. Efficacy of high dose topical
      corticotherapy].
AB  - INTRODUCTION: A chronic pruriginous eruption of eosinophil-rich follicular
      papules and pustules is observed in AIDS patients. The pathogenesis of this
      disease, termed eosinophil folliculitis, is poorly understood and treatment is
      debated. CASE REPORT: A 30-year-old woman with AIDS developed highly pruriginous
      lesions of 5 month duration localized on the face, the trunk and upper limbs.
      There were papulo-pustules and excoriated papules. The elementary lesion was a
      follicular pustula. The eosinophil count was normal. The pathology examination
      revealed a rich eosinophil infiltration around the hair follicles and sebaceous
      glands as well as follicular spongiosis. Search for demodex, pityrosporons and a
      large number of infectious agents was negative. Oral minocyclin was uneffective.
      Local high-dose corticosteroids produced a remarkable effect and led to complete
      remission in 9 months. DISCUSSION: Most cases of eosinophil folliculitis
      associated with AIDS have been reported in men, but rarely in Europe. The
      remarkable efficacy of the local corticosteroid in this case was exceptional.
      This condition could result from inappropriate inflammatory reaction in AIDS
      induced by various factors including demodex and pityrosporon. Several
      therapeutic approaches have been proposed to eradicate the triggering factors and
      others to modify the immune response. The exceptional response to the short local
      treatment with corticosteroids would suggest that this approach could be proposed
      as first intention treatment in eosinophil folliculitis associated with AIDS.

PMID- 9033715
TI  - [Multicentric histiocytosis with hematological involvement].
AB  - INTRODUCTION: The aim of this work was to present a case of multicentric
      histiocytosis with haematologic involvement. CASE REPORT: A 68-year-old man
      presented with poor general health and a nodular eruption of the skin and larynx.
      On clinical examination there was an enlarged spleen and laboratory results
      revealed an inflammatory syndrome, platelet count 60,000 and myelemia with 10 p.
      100 immature elements in a white cell count of 14,000. Pathology and
      ultrastructure examinations led to the diagnosis of multicentric histiocytosis.
      Bone marrow aspiration was normal. Pancytopenia then developed with bone marrow
      hypoplasia without infiltration. Corticosteroids then cyclophosphamide were
      uneffective for either the skin disease or the hematologic disorder. The patient
      developed severe buccal aphthosis which responded well to thalidomide. This
      treatment reduced the size and the number of skin nodules. Finally, renal failure
      of unknown origin was observed. DISCUSSION: Electron microscopy is essential for
      positive and differential diagnosis of atypical multicentric histiocytosis.
      Hematological disorders associated with multicentric histiocytosis may either be
      specific or totally independent.

PMID- 9033713
TI  - [Toxicoderma caused by prednisone and prednisolone. Value of skin tests in the
      screening of cross sensitivity].
AB  - INTRODUCTION: Allergic reactions to general corticosteroid therapy are uncommon.
      CASE REPORT: We report a patient with systemic lupus erythematousus who developed
      skin rash after initiation of prednisone then prednisolone therapy. Histology
      evidence suggested leukocytoclastic vasculitis. The skin tests (prick tests,
      intradermoreactions and patch-tests) using a battery of injectable
      corticosteroids showed a highly positive reaction to prednisolone,
      methylprednisolone and dexamethasone on the intradermo-reactions 24 hours later.
      Histology examination of a positive-response showed leukocytoclastic vasculitis
      associated with eczematiform alterations of the epidermis compatible with a drug
      reaction. The skin tests however were negative for betamethasone, triamcinolone,
      paramethasone and hydrocorticose. The patient was treated with betamethasone and
      no skin reaction was observed. DISCUSSION: Skin tests, particularly intradermo
      reactions read 24 hours later would appear to be useful in identifying possible
      cross-sensitivity.

PMID- 9033712
TI  - [Oxiconazole cream versus ketoconazole cream. A prospective, randomized, double
      blind, multicenter study in the treatment of inguinocrural dermatophytoses].
AB  - INTRODUCTION: The aim of this study was to compare oxiconazole, 1 p. 100 cream,
      with ketoconazole, 2 p. 100 cream, applied once-daily, in the treatment of tinea
      cruris. PATIENTS AND METHODS: A prospective, randomized, double-blind trial was
      performed in 8 dermatology departments on two parallel groups in patients having
      this type of mycosis confirmed by mycological examination. RESULTS: The efficacy
      was analyzed in 66 out of the 79 patients included in the study (36 patients
      treated with oxiconazole, 30 with ketoconazole). At Day 14, a first assessment
      was made and 77.1 p. 100 of the patients treated with oxiconazole had been cured;
      this result was significantly better (p < 0.05) than that obtained with
      ketoconazole (51.7 p. 100 of cured patients). At Day 21, after a further week of
      treatment, both treatments were efficient with statistically non-different
      results between the two groups: 97.2 p. 100 of the patients treated with
      oxiconazole, versus 86.7 p. 100 with ketoconazole. Thus, a greater rapidity of
      action of oxiconazole was observed. No correlation was detected between the ratio
      of cured patients and the duration of the mycosis. The safety was assessed in 74
      patients. No adverse effects were reported for the patients treated with
      oxiconazole, whereas 9 patients treated with ketoconazole experienced contact
      sensitization reactions and irritant skin reactions due to the application of the
      product. The difference between the two groups of treatment was statistically
      greatly significant (p < 0.001). Furthermore, acceptance of the drug on the part
      of the patient was better (p < 0.05) with oxiconazole. DISCUSSION: After 3 weeks
      of topical treatment oxiconazole has revealed itself to be as efficient as
      ketoconazole, but it seems more rapidly efficient and better tolerated than
      ketoconazole.

PMID- 9033716
TI  - [Post-radiotherapy cutaneous neuro-endocrine carcinoma].
AB  - INTRODUCTION: Merkel cell carcinoma or cutaneous neuroendocrine carcinoma is an
      uncommon severe disease. The carcinogenic effect of ionizing radiations has been
      suspected in exceptional observations. We report the sixth case of Merkel cell
      neuroendocrine carcinoma in a patient with prior radiotherapy. CASE REPORT: An 86
      year-old man underwent radiotherapy for a basal cell carcinoma of the tip of the
      nose and developed a highly aggressive Merkel cell carcinoma at the same location
      6 years later. DISCUSSION: The development of Merkel cell carcinoma on irradiated
      tissue accounts for 2.6 p. 100 of the 227 publications where dermatological
      history was reported. This percentage may be underestimated. The similar
      localizations of the irradiated zone and the site of cancer development 5 years
      later suggest that the Merkell cell carcinoma may be a radio-induced tumor. The
      delay may vary from 5 to 47 years. The similarity of the carcinogenic factors
      involved in Merkel cell carcinoma and squamous cell or basal cell carcinomas
      (ultraviolet, ionizing irradiation) and the frequent association of different
      types favor an epidermal origin for Merkel cell carcinoma. In clinical practice,
      past history of radiotherapy in an area where Merkell cell carcinoma develops
      indicates that therapeutic management must exclude post-operative radiotherapy.

PMID- 9033717
TI  - [Deep morphea-type lesions, first manifestations of lymphocytic lymphoma].
AB  - INTRODUCTION: The association between scleroderma and lymphoma is uncommon and
      can sometimes query an fortuitous association. More particular are observations
      where chronological and histological features show an evident link between a
      tumorous process and sclerosis. OBSERVATION: This case concerns a man 69 years
      old who was treated for one year for partial subcutaneous sclerosis present on
      his legs, thighs, fore-arms, and on the upper part of the trunk. No signs were
      present of visceral involvement evoking a systemic scleroderma and histology
      showed an intrication of a deep sclerosis, fasciitis and a tumoral lymphoma
      process. Diagnosis of lymphocytic lymphoma was confirmed. Initiating a
      chemotherapy (CHOP) allowed for a reduction of the sclerosis which didn't respond
      to the only corticotherapy. DISCUSSION: This observation can be linked to the
      association of fasciitis and lymphoma identified by Naschitz et al, but is
      different by: 1) the clinical aspect which correspond more to deep morphea
      lesions; 2) the histological link between sclerosis and lymphoma. This last point
      suggest that it is the tumoral population which have induced the sclerosis
      process linked to the secretion of pro-inflammatory factors. In adverse cases
      with longer delay between lymphoma and scleroderma this association may be
      fortuitous.

PMID- 9033718
TI  - [Cutaneous localizations of chronic lymphoid leukemia in a zona area].
AB  - INTRODUCTION: Leukemia cutis is a rare event in B-cell chronic lymphocytic
      leukemia. CASE REPORT: A patient with B-cell chronic lymphocytic leukemia
      developed leukemia cutis at the site of prior cervical (C2-C3) herpes zoster.
      DISCUSSION: Leukemia cutis on prior site of herpes zoster is exceptional. It
      should be differentiated from non specific skin reactions secondary to herpes
      zoster.

PMID- 9033719
TI  - [Subcutaneous cysticercosis].
AB  - INTRODUCTION: The case of a patient originated from Angola who presented
      subcutaneous and neurologic cysticercosis is reported. OBSERVATION: The patient
      was referred for the etiological diagnosis of recurrent seizures. The diagnosis
      was made by histologic examination of a subcutaneous lesion. COMMENTS: We review
      the clinical characteristics of subcutaneous cysticercosis. The association of
      subcutaneous nodules and signs of central nervous involvement occurring in a
      patient originating from an area where cysticercosis is endemic, must be
      suspected of cysticercosis.

PMID- 9033720
TI  - [Metastatic epidermoid carcinoma in idiopathic CD4+ T lymphocytopenia syndrome].
AB  - INTRODUCTION: Skin cancers are more frequent and more aggressive in
      immunosuppressed patients. CASE REPORT: A 58-year-old man was seen in January
      1994 for squamous cell carcinoma of the right shoulder which had grown to 7 x 7
      cm in the last 5 months. The patient had a past history of surgical exeresis of 5
      squamous cell carcinomas and 3 basal cell carcinomas. Despite complete exeresis,
      the disease spread to localized then diffuse skin metastases. Acitretine and
      alpha-interferon were uneffective. Polychemotherapy stabilized the situation but
      several bronchopulmonary infections with atypical germs led to death (in February
      1995). The patient had CD4 lymphocytopenia with a count < 100/mm3 in January 1994
      of unknown origin (viral infection was eliminated). DISCUSSION: Our patient had
      idiopathic CD4 lymphocytopenia. In 40 p. 100 of the cases CD4 lymphocytopenia is
      caused by AIDS and in 53 p. 100 by other diseases, especially skin diseases
      including Kaposi syndrome, mycosis fungoides, squamous cell or basal cell
      carcinoma. The cutaneous carcinomas which often develop in AIDS patients with low
      CD4 counts are usually less aggressive than in our patient. Certain neoplasia
      could be the cause of the lymphopenia. CD4 counts are usually more variable and
      lymphopenia of shorter duration in other etiologies.

PMID- 9033721
TI  - [Paraneoplastic pemphigus in chronic lymphocytic leukemia].
AB  - INTRODUCTION: Paraneoplastic pemphigus is an autoimmune bullous disease described
      by precise clinical, histological and immunological features presented by Anhalt
      in 1990. Prognosis is very severe and depends on the associated neoplasia and the
      gravity of the mucosal damage. CASE REPORT: Paraneoplastic pemphigus was
      diagnosed in a 62-year-old man with chronic lymphoid leukemia. The course was
      favorable up to one-year follow-up after general corticosteroid therapy.
      DISCUSSION: This case illustrates that paraneoplastic pemphigus can be controlled
      by general corticosteroids and would suggest the severe prognosis may be
      improved.

PMID- 9033722
TI  - [Localized bilateral and symmetrical neurofibromatosis].
AB  - INTRODUCTION: We report the first case of bilateral neurofibromatosis localized
      distally on the lower limbs. CASE REPORT: A 36-year-old woman presented about 20
      nodular lesions of the plantar and both lateral aspects of both feet which
      developed progressively after age 30. Histology examination evidenced
      neurofibromas. Clinical features and laboratory results enabled us to eliminate
      von Recklinghausen disease in this mother of 3 children. DISCUSSION: This
      observation allowed us to situate symmetrical and bilateral neurofibromatosis in
      the Riccardi classification for genetic counselling. We conclude that the case
      was a type V neurofibromatosis in a sporadic bilateral form, rarely reported in
      the literature.

PMID- 9033724
TI  - [A case for diagnosis: umbilical metastasis].

PMID- 9033723
TI  - [Light and heavy chain deposition disease with cutaneous and renal
      manifestations].
AB  - INTRODUCTION: Monoclonal light and heavy chain deposition disease is a rare
      syndrome distinct from light chain amyloid, which is defined by the presence of
      monoclonal deposits of immunoglobulins in various tissues. CASE-REPORT: A 65-year
      old man presented with renal symptoms due to membranoproliferative
      glomerulonephritis, associated with urticarial papules located on the arms and
      back. Histological examination of a skin biopsy specimen showed lymphocytic
      vasculitis. Direct immunofluorescence examination of kidney and skin lesions
      using anti-gamma 2 and anti-Kappa monoclonal antibodies, showed a similar
      staining on the basement membrane zone and vessel walls. COMMENTS: As far as we
      know, this is the first documentation of monoclonal light and heavy chain
      deposition disease associated with a lymphocytic skin vasculitis and renal
      involvement caused by similar monoclonal deposits of immunoglobulins in the
      kidney and skin.

PMID- 9033725
TI  - [A case for diagnosis: Proteus syndrome].

PMID- 9033726
TI  - [Eosinophilia and skin: current data].

PMID- 9033727
TI  - [New phototherapies].

PMID- 9033728
TI  - [Apropos of juvenile palmar dermatitis of swimming pools].

PMID- 9033729
TI  - [Monthly question: should we buy a dermatoscope?].

PMID- 9033730
TI  - [Percutaneous thoracic sympathectomy under x-ray computed tomographic control in
      hyperhidrosis and refractory ischemia. Apropos of 17 cases].
AB  - We report our experience with percutaneous thoracic sympathectomy using computed
      tomography-guided injection of phenol in 17 patients. A total of 24 neurolyses
      were performed in outpatients. Indications were palmo-plantar hyperhidrosis in 10
      patients and severe Raynaud phenomena in 7 cases (Sharp's syndrome = 2.
      sclerodermia = 3, Raynaud's syndrome = 1, digital arteritis = 1). Conventional
      treatment had failed in all patients. Cure was obtained in all cases of
      hyperhidrosis. For the patients with critical ischemia, there was temporary
      improvement which allowed wound healing, but recurrence was the rule within 6
      months on average. Complications included pneumothorax, brachial nevralgia which
      persisted for 4 months and 3 partial Claude-Bernard-Horner syndromes. This
      technique is an inexpensive reliable method which can be used in case of
      contraindications or to avoid certain complications of endoscopic surgery which
      remains the standard treatment. Percutaneous sympatholysis in thus an interesting
      simple alternative.

PMID- 9033731
TI  - [Acute cholecystitis in periarteritis nodosa. 8 cases].
AB  - OBJECTIVES: Analyze clinical manifestations and laboratory findings in patients
      with periarteritis nodosa who developed acute cholecystitis in order to determine
      their value for prognosis and management. PATIENTS AND METHODS: We report 8 cases
      of acute cholecystitis which revealed or occurred as a complication of
      periarteritis nodosa. These were 4 men and 4 women, mean age 50 years.
      Periarteritis nodosa was diagnosed on the basis of histological evidence and/or
      clinical expression. Complimentary explorations included: sonography of the
      biliary tree, cholecystogram or cholangiogram in addition to diagnostic work-up
      for periarteritis nodosa. RESULTS: The clinical or sonographic presentation was
      similar to common cases of cholecystitis. However, no stone were observed in 2/8
      cases. Histologically, the gall bladder showed characteristic vascular lesions
      suggestive of periarteritis nodosa in 7 out of 8 cases (no operation in 1 case).
      Cholecystitis was the inaugural sign in 2 cases. Surgery was performed for
      lithiasic forms. Medical management with methylprednisolone i.v. was used
      successfully in the alithiasic forms. In the 2 cases with inaugural solitary
      acute cholecystitis. lithiasis was found in the surgical specimen in 1 case; the
      pathology examination gave the etiological diagnosis. There was no lithiasis in
      one case with inaugural cholecystitis. CONCLUSIONS: The development of acute
      cholecystitis in patients with periarteritis nodosa is uncommon but should be
      treated surgically in case of lithiasis or when the cholecystitis is the
      inaugural sign. Unlike digestive tract involvement, periarteritis nodosa does not
      aggravate the clinical course. Alithiasic forms may be treated medically with
      corticosteroids. In our opinion, therapeutic abstention, sometimes proposed in
      patients with necrotizing angiitis of the gall bladder, is not always indicated
      as some patients can benefit from medical treatment of the underlying
      periarteritis nodosa.

PMID- 9033733
TI  - [Interview with Gilbert Fournie. What is going to happen tomorrow in the field of
      physiopathology of systemic lupus erythematosus?].

PMID- 9033732
TI  - [Difference in costs of autologous transplantation of peripheral and bone marrow
      hematopoietic stem cells. A retrospective analysis over 1 year of transplantation
      in lymphoma, Hodgkin's disease and myeloma in a Center].
AB  - The study analysed the financial benefits of transplantation with peripheral
      blood stem-cells primed after chemotherapy and growth factor in comparison with
      bone marrow transplantation. Twenty-three consecutive transplantations were
      performed during one year: 14 peripheral blood stem-cell (CSC group) and 9 bone
      marrow transplantations (MO group). No differences in patients characteristics
      were seen between the two groups except for higher number of "BEAM" conditioning
      in CSC group. Were analyzed delay in neutrophil and platelet recovery, numbers of
      days in hospital, with fever, under antibiotics, costs of supportive therapy,
      stem-cell collection and cryopreservation. Difference was significant for
      duration of neutropenia with advantages in CSC group, but the number on days in
      hospital, with fever or under antibiotics were similar. Number of platelet
      transfusions was reduced in CFC group: this economical advantage was lost with
      the cost of growth factor used for priming stem-cells stem-cell collections and
      cryopreservations. In our retrospective study, financial advantages associated to
      peripheral blood stem-cell transplantation was not verified.

PMID- 9033735
TI  - [Risk factors of cerebral toxoplasmosis in patients with HIV infection.
      Definition of indications of primary prevention].

PMID- 9033734
TI  - [Desensitization to trimethoprim-sulfamethoxazole in patients with HIV
      infection].
AB  - OBJECTIVE: To evaluate the safety and efficacy of an in-patient oral
      desensitization regimen in HIV- infected patients hypersensitive to trimethoprim
      sulfamethoxazole (TMP-SMX). METHODS: TMP-SMX was given orally once a day using
      incremental doses every day, starting with 0.4 mg TMP/2 mg SMX at day 4 and
      achieving a full dosage of TMP-SMX (80 mg/400 mg) at day 5. Success was defined
      as clinical tolerance of the final dose for more than 10 days following
      completion of the procedure. RESULTS: Desensitization was successfully completed
      in 29 of 30 patients. A transient rash occurred in one patient during
      desensitization and resolved without need for discontinuation of the
      desensitization protocol. The procedure failed in one patient who experienced
      sustained moderate cutaneous reaction with fever on day 5. CONCLUSIONS: Our
      results suggest the safety and efficacy of an inpatient oral desensitization
      regimen in 30 HIV-infected patients who had experienced cutaneous reactions to
      trimethoprim-sulfamethoxazole (TMP-SMX). Specific desensitization to TMP-SMX
      allows to circumvent the limitations towards effective prophylaxis of PCP that
      are dependent on the occurrence of cutaneous reactions to the drug.

PMID- 9033736
TI  - [Lipoprotein anomalies in HIV infections].
AB  - Alterations in lipid parameters occur during many acute infections. Different
      studies suggest that variations in lipid parameters can be used as markers of the
      progression of human immunodeficiency virus (HIV) infection. Hypocholesterolemia
      is observed in asymptomatic HIV+ subjects, then hypertriglyceridemia appears in
      patients with AIDS. Several hypotheses have been raised concerning the potential
      causes and consequences of these modifications. Cytokine effects on different
      enzymes of lipid metabolism, studied in vitro and in vivo, are thought to be
      partially responsible for the dyslipidemia. Hypertriglyceridemia could
      participate in cachexia and dementia could be facilitated by the changes in
      cholesterol metabolism. The use of the lipid parameters is proposed in HIV
      positive subjects, especially during anti-viral treatment.

PMID- 9033737
TI  - [Portal thrombosis, mesenteric infarction and anticardiolipin antibodies in a
      patient with AIDS].

PMID- 9033738
TI  - [Isolated Kaposi sarcoma of the small intestine disclosed by occlusion in an HIV
      positive patient].

PMID- 9033739
TI  - [Cerebrovascular complication caused by aortic atheroma].
AB  - The aorta is the most frequent site for atherosclerosis, and is more frequent
      than the internal carotids or cerebral arteries. Transesophageal echocardiography
      has made it possible to identify atheromatous lesions of the aortic arch which
      are situated before the branches to the neck vessels and are capable of causing
      embolic cerebral events. These atheromatous plaques can be irregular, may
      protrude into the aortic lumen and sometimes have loose thrombus attached to
      them. The risk of strokes and transient ischemic attacks appears to be higher
      when plaques are more than 4 mm in thickness and when mobile components are
      present. Atheroma in the ascending aorta and aortic arch is a significant risk
      factor for cerebral ischemia, independent of high-grade carotid stenosis. Aortic
      atherosclerotic lesions should particularly be looked for in patients with a
      history of repeated peripheral and cerebral embolism, in whom no obvious embolic
      cause is found. A standard protocol for treatment of these potentially embolic
      aortic lesions has not yet been agreed upon, but the use of antiplatelet drugs or
      vitamin-K antagonists treatment should be considered.

PMID- 9033740
TI  - [Hyperhomocysteinemia, atherosclerosis and arterial and venous thrombosis].

PMID- 9033741
TI  - [Aortitis in Horton disease. Review of the literature].
AB  - First described in 1937, giant cell aortitis (aortitis associated with giant cell
      arteritis) occurs in 20 to 40% of patients with giant cell arteritis and is often
      clinically silent. Temporal involvement usually precedes aortic involvement. The
      process may involve the entire aorta, but complications are usually related to
      thoracic involvement. Patients with giant cell aortitis may be asymptomatic, or
      present with aortic arch syndrome, dilation of the aorta, aortic aneurysm, aortic
      dissection, sudden rupture of the aorta, or aortic valve incompetence. Thoracic
      aneurysms are usually fusiform and can be complicated by dissection in up to 50%
      of patients. Aortic involvement may be the presenting feature of giant cell
      arteritis: it may also occur in patients with preexisting temporal arteritis,
      often when corticosteroid therapy is reduced or discontinued. Aortic rupture
      complicating aortitis may be the cause of death in 3-12% of patients with giant
      cell arteritis. Clinical follow-up with assessment of disease activity by chest X
      ray and biological markers of inflammation should be performed yearly in giant
      cell arteritis. Aortic involvement should be suspected if cardiac or vascular
      echo-Doppler shows evidence of an aortic arch syndrome, aortic dilation,
      aneurysm, or of aortic valve incompetence. Corticosteroid therapy, beginning with
      a dose of 1 mg/kg/day remains the key point of therapy. The dose is subsequently
      adjusted based on the clinical course and the results of ancillary tests. This
      treatment might prevent fatal outcome with aortic rupture. Long-term follow-up of
      all patients with giant cell arteritis or polymyalgia rheumatica is essential, as
      complications may develop late in the course of the disease.

PMID- 9033742
TI  - [Amiodarone-induced hypothyroidism followed by hyperthyroidism. Apropos of 2 new
      cases].
AB  - Amiodarone, an iodine-rich benzofuranic derivative, may often induce
      hyperthyroidism and hypothyroidism. We report two cases of complex dysthyroidism,
      in which hypothyroidism and then hyperthyroidism alternated: we recall five
      former observations found in the literature. Their nosologic position and
      pathophysiologic mechanisms are discussed.

PMID- 9033743
TI  - [Use of colchicine in periodic disease].

PMID- 9033745
TI  - [Staphylococcus lugdunensis endocarditis. A new case].

PMID- 9033744
TI  - [IgM anti-MAG neuropathy with involvement of the cranial nerves disclosing B-cell
      lymphoma].

PMID- 9033746
TI  - [Tuberculosis and rheumatoid arthritis. Apropos of 4 cases].

PMID- 9033747
TI  - [Metastatic sites of colonic adenocarcinoma in the ORL system: 2 cases].

PMID- 9033748
TI  - [Splenic rupture after colonoscopy].

PMID- 9033749
TI  - [Towards the search of an optimal indicator of anesthetic activity].

PMID- 9033750
TI  - [New regulations of blood transfusion in France].

PMID- 9033751
TI  - [Definition of a diagnostic score of malignant hyperthermia using P-31 magnetic
      resonance spectroscopy].
AB  - OBJECTIVES: To assess the metabolic muscular disorders associated with malignant
      hyperthermia (MH) using 31-P MRS, in order to develop a diagnostic tool for MH.
      STUDY DESIGN: Retrospective analysis of a series of case. PATIENTS: Group of 39
      subjects, including 13 MH susceptible (MHS), and 26 not susceptible (MHN) members
      of recognized MHS families, according to the results of the in vitro contracture
      tests. METHODS: Each subject underwent two protocols, both including rest,
      exercise and recovery periods. Exercise was performed successively under aerobic
      and ischaemic conditions. RESULTS AND DISCUSSION: A significant early acidosis
      was recorded for the MHS group under both conditions of exercise (normoxia and
      ischaemia). However, the sensitivity of this parameter (77%) was not high enough
      to be considered as discriminant. Therefore a MRS score has been defined,
      corresponding to the sum of metabolic anomalies (acidosis, anomalies in PCr tum
      over and in ATP or phosphomonoesters concentrations) recorded throughout both
      protocols. This score provided satisfactory results for both sensitivity (93%)
      and specificity (93%). CONCLUSION: 31-P MRS can act as a reliable diagnostic tool
      for MH.

PMID- 9033753
TI  - [Programmed autologous blood transfusion in children. Results of a national
      survey].
AB  - OBJECTIVE: To assess the development and the current practice of predeposit
      autologous blood transfusion (PABT) in children in France. STUDY DESIGN:
      Nationwide survey with a questionnaire. METHOD: Survey conducted in January 1995,
      including 121 blood transfusion centres (BTC) out of which 101 replied. RESULTS:
      Initiated in 1979, PABT is practiced at present in 66% of BTC. This figure
      increased by 12% from 1993 to 1994. Orthopaedic surgery was the main indication.
      Other indications included bone marrow harvesting for allogenic transplantation.
      Concerning the inclusion criteria, the lower limit of age was 9 +/- 4 years and
      weight 26 +/- 10 kg. The youngest child was one-year-old and his body weight was
      8 kg. CONCLUSION: The production of codified protocols would probably favour the
      development of PABT in children and increase its safety and its efficiency.

PMID- 9033752
TI  - [Effects of propofol on blood concentration of cyclosporine].
AB  - OBJECTIVE: This study was designed to assess whether propofol modifies the blood
      concentrations of cyclosporine and lipoproteins, which bind cyclosporine. STUDY
      DESIGN: Prospective open study. PATIENTS: Fifteen consecutive grafted patients,
      scheduled for surgery allowing them to resume their oral treatment
      postoperatively. Their immunosuppressive treatment, included cyclosporine (Cy A),
      at a steady-state dosage. METHODS: Blood samples were drawn and residual Cy A
      blood concentrations were measured the days before and after anaesthesia and
      before and immediately after discontinuing the propofol infusion. Serum
      triglycerides, cholesterol, high-density lipoprotein (HDL) concentrations were
      measured before and immediately after discontinuing the propofol infusion.
      RESULTS: The 15 patients were given propofol by infusion for 30-210 min (mean 85
      +/- 59 min). They received a total dose of propofol of 696 +/- 497 mg, a total
      fentanyl dose of 175 +/- 82 micrograms, and a total midazolam dose of 2.8 +/- 0.8
      mg. The residual cyclosporine blood concentrations were similar the day before
      (142 +/- 47 ng.mL-1) and following anaesthesia (128 +/- 46 ng.mL-1) (P = 0.08).
      Serum cholesterol concentrations were not significantly influenced by propofol
      infusion, but serum triglycerides levels increased (1.46 +/- 0.66 vs 1.97 +/-
      0.81 g.L-1), and HDL and LDL levels decreased (0.54 +/- 0.20 vs 0.47 +/- 0.18 g.L
      1; 1.44 +/- 0.42 vs 1.28 +/- 0.37 g.L-1). CONCLUSION: Propofol by infusion does
      not modify the cyclosporine concentration. It is concluded that propofol may be a
      suitable agent for intravenous anaesthesia in cyclosporine treated patients,
      provided a close postoperative monitoring of cyclosporine blood concentrations is
      maintained.

PMID- 9033755
TI  - [Evaluation of anesthetic activity in the operating room. Use of beta relative
      cost index].
AB  - OBJECTIVE: To evaluate the anaesthetic activity in the operating rooms using the
      newly reconstructed RCI beta, or relative cost index beta, a specific tool for
      analysis of anaesthetic activity and the linked cost. STUDY DESIGN: Prospective
      multicentric survey. METHODS: All scheduled anaesthetic procedures performed in
      March 1995 were collected. RCI beta items were entered in a standardized data
      base. Gender, age group, time of admission to the operating room, time of
      incision, time of exit from the operating room, and the code number of the
      surgical or radiological procedure were added on request of the steering
      committee. RESULTS: Complete responses were obtained from 35 out of the 37
      contacted departments. A total of 31,391 procedures were analysed. Only 14% of
      patients were of ASA class over 2. Anaesthetic practices were comparable between
      institutions. Only the incidence of special circumstances and techniques was
      higher in University hospitals. General anaesthesia was the most widely used
      technique (76.58%). A large proportion (19%) of anaesthetics were given for
      endoscopy and radiology. More than 87% of patients were monitored postoperatively
      in recovery areas. There was a lower correlation between the theoretical standard
      duration and median actual duration of the perioperative period than the
      operative period (r = 0.54 vs r = 0.81). DISCUSSION: Part of our activity could
      be described with RCI beta. The obtained data allow a comparison of anaesthetic
      activity in the operating rooms of different hospitals, departments and units.
      Further analysis of these data will also provide information about the types of
      surgical procedures and the level of global activity.

PMID- 9033754
TI  - [Nosocomial infections in a burns unit. Results of a prospective study over a
      year].
AB  - OBJECTIVES: To assess nosocomial infections in a burn care centre, to identify
      patients' infection risk factors at the time of admission and factors of monthly
      variations of infection incidence. STUDY DESIGN: Prospective survey, from October
      1992 to September 1993. PATIENTS AND METHOD: The study included 140 patients
      staying for more than two days in a 22-bed burn unit. Nosocomial infection
      criteria were derived from the 1988 CDC criteria. Incidence rates of infection
      were calculated. Infected and noninfected patients were compared. Each monthly
      infection incidence was compared with six unit activity indicators. RESULTS:
      Fifty-six patients developed 132 infections. The overall incidence was 94%.
      Incidence density was 25 infections per 1,000 days of care. The distribution of
      infected sites was: skin (30%), intravascular catheters (25%), blood (22%),
      urinary tract (18%), respiratory tract (5%). The most frequent pathogens were
      Pseudomonas sp (49%), Staphylococcus sp (18%), Escherichia coli (18%), and
      Streptococcus faecalis (10%). They were characterized by a good antibiotic
      sensitivity. Each common burn severity index was predictive of nosocomial
      infections. Facial, perineal and respiratory lesions were also linked to
      infection. There was a positive correlation between the peak of nosocomial
      infections in the unit during a month and the peak of activity during the
      foregoing one. CONCLUSION: Incidence rates of infection were high, as 40% of the
      population was concerned. Choosing reliable infection criteria was the most
      difficult problem to solve.

PMID- 9033757
TI  - [Prevention of respiratory complications after abdominal surgery].
AB  - Abdominal surgery, especially upper abdominal surgical procedures are known to
      adversely affect pulmonary function. Pulmonary complications are the most
      frequent cause of postoperative morbidity and mortality. This review article
      aimed to analyse the incidence and risk factors for postoperative pulmonary
      morbidity and their prevention. The most important means for preoperative
      assessment is the clinical examination; pulmonary function tests (spirometry) are
      not reliably predictive for postoperative pulmonary complications. Age, type of
      surgical procedure, smoking and nutritional state have all been identified as
      potential predictors for postoperative complications. However, usually there is
      not enough preoperative time available to obtain beneficial effects of stopping
      smoking and improvement of nutritional state. In patients with COPD, a
      preoperative multidisciplinary evaluation including the primary care physician,
      pulmonologist/intensivist, anesthesiologist and surgeon is required. Consensus as
      to preoperative physiologic state, therapeutic preparation, and postoperative
      management is essential. Simple spirometry and arterial blood gas analysis are
      indicated in patients exhibiting symptoms of obstructive airway disease. There
      are no values that contra-indicate an essential surgical procedure. Smoking
      should stop at least 8 weeks preoperatively. Preoperative therapy for elective
      surgery with antibiotics, beta2-agonist, or anticholinergic bronchodilator
      aerosols, as well as training in cough and lung expansion techniques should begin
      at least 24 to 48 hours preoperatively. Postoperative therapy should be continued
      for 3 to 5 days. Usually, anaesthesia is responsible for early complications,
      whereas surgical procedures are often associated with delayed morbidity.
      Laparoscopic procedures are recommended, as postoperative morbidity and hospital
      stay seem reduced in patients without COPD. Regional anaesthesia is given as
      having less adverse effects on pulmonary function than general anaesthesia.
      However, for unknown reasons these benefits are not associated with a decrease in
      postoperative respiratory complications. Moreover, the quality or the type of
      postoperative analgesia does not influence postoperative respiratory morbidity.
      Postoperatively, oxygen administration increases SaO2, but cannot abolish
      desaturation due to obstructive apnea. The various techniques of physiotherapy
      (chest physiotherapy, incentive spirometry, continuous positive airway pressure
      breathing) seem to be equivalent in efficacy; but intermittent positive pressure
      breathing has no advantages, compared with the other treatments and could even be
      deleterious. Chest physiotherapy and incentive spirometry are the most practical
      methods available for decreasing secretion contents of airways, whereas
      continuous positive airway pressure breathing is efficient on atelectasis. In
      stage II or III COPD patients, admission in a intensive therapy unit and
      prolonged mechanical ventilation may be required.

PMID- 9033756
TI  - [A survey of the diffusion and impact of consensus development conference on
      infections caused by central venous catheters in an anesthesiologist team].
AB  - OBJECTIVES: To assess the diffusion and the impact on the professional practices
      of a consensus conference (CC) by the French speaking Society of Intensive Care
      on "Central venous catheter-related sepsis in intensive care". STUDY DESIGN:
      Before-after survey with two successive questionnaires. MATERIAL AND METHODS: Two
      questionnaires (Q1 and Q2) were circulated either to intensivists (group 1) or to
      anaesthetists (group 2) of a University Hospital, before (Q1) and after (Q2)
      distribution of the CC conclusions. They aimed to assess the diffusion of the
      conclusions by the CC; the professional practices before the CC and their
      modifications after consideration of the recommendations by the CC. RESULTS: Out
      of the 55 consulted, 85% answered Q1, and 71% Q2. Among them, 42% were aware of
      the conclusions of the CC before starting the survey-73.5% from group 1 and 28%
      from group 2. Therefore, conversely to anaesthetists, intensivists, did not
      significantly modify their professional practices after consideration of the CC
      conclusions. CONCLUSION: This study shows a satisfactory diffusion of the content
      of jury's recommendations among anesthetists whereas the impact was less
      satisfactory with intensivists. The impact of a CC could probably be improved by
      a better diffusion of the consensus statements and by the intervention of local
      linkmen.

PMID- 9033758
TI  - [Neurotoxicity of intrathecally administrated agents].
AB  - Spinal anaesthetics can induce histopathologic lesions and regional haemodynamic
      alterations in the spinal cord. There are numerous causes of neurologic lesions,
      including direct trauma of the spinal cord and nerve roots during puncture or
      catheter insertion, compromised spinal cord perfusion and direct neurotoxic
      effect. Histopathologic lesions are localized either in meninges (meningitis or
      arachnoiditis) or in neuraxis (myelitis or axonal degeneration). Neurotoxicity
      can result from decrease in neuronal blood supply, elicited by high
      concentrations of the solutions, long duration exposure to local anaesthetics,
      and the use of adjuvants. They have been implicated in the occurrence of cauda
      equina syndrome after continuous spinal anaesthesia using hyperbaric solution of
      lidocaine and tetracaine given through small diameter catheters. Selective spinal
      analgesia is induced by spinal opioids without motor blockade except for
      meperidine. Complications occurred in patients after high doses of morphine,
      which were related to one of its metabolites, morphine-3-glucuronide.
      Preservative-free opioid solutions are to be preferred for spinal anaesthesia.
      There is no report of neurotoxicity neither in animal studies, nor in humans,
      using spinal clonidine. In order to reduce the incidence of neurotoxicity, some
      safety rules should be followed. The lowest efficient dose of local anaesthetics
      must be given. Incomplete blockade should not necessarily lead to a reinjection.
      Large volume of hyperbaric lidocaine or repeated injections of such solutions
      must be avoided as well as preservative-containing solutions. The administration
      of new compounds by the spinal route must be supported by data of spinal
      neuropharmacology and the lack of neurotoxicity must have been previously checked
      with animal studies.

PMID- 9033759
TI  - [Severe hyperthermia caused by sudden withdrawal of continuous intrathecal
      administration of baclofen].
AB  - Baclofen is used for the treatment of post-traumatic spasticity. It carries a
      risk of overdose as well as of an acute withdrawal syndrome. We report two cases
      of severe hypertonia and hyperthermia (> 42 degrees C), occurring after
      accidental discontinuation of intrathecal infusion of baclofen. Both hypertonia
      and hyperthermia ceased when administration of baclofen was resumed. In parallel,
      the patients developed transient life-threatening alterations of hepatic
      (cytolysis), haematologic (coagulopathy) and cardiorespiratory functions for some
      days. It is concluded that the occurrence of such a withdrawal syndrome should be
      prevented, especially in patients with chronic intrathecal administration and
      first symptoms should be recognized without delay. Relationships with other
      malignant hyperthermias are discussed.

PMID- 9033760
TI  - [Serotonin syndrome in acute poisoning with antidepressive agents].
AB  - We report a case of severe serotonin syndrome after self-poisoning with two
      antidepressant drugs, paroxetine (a selective inhibitor of serotonin reuptake)
      and moclobemide (a reversible inhibitor of MAO-A). The serotonin syndrome is
      characterized by neuromuscular, behavioural, and autonomic changes. It occurs
      with the use of drugs able to increase serotonergic transmission in brain by
      acting on biosynthesis, reuptake, catabolism or release of serotonin. Treatment
      is symptomatic. The incidence of severe cases seems to have increased, probably
      due to the use of new antidepressant "specific" inhibitors of the serotonin
      reuptake.

PMID- 9033761
TI  - [Thrombolytic therapy with rt-PA of recurrent thrombosis in tricuspid valve
      prosthesis during pregnancy].
AB  - The authors report a case of a woman who had two episodes of a tricuspid Saint
      Jude prosthesis thrombosis treated with fibrinolysis using rt-PA, during the
      fourth month of pregnancy. A first course of thrombolytic therapy was successful
      with normal valve function despite threatening abortion and uterine bleeding. An
      early rethrombosis of the prosthetic valve and a failure of a second course of
      thrombolysis required the interruption of pregnancy with a replacement of the
      tricuspid valve prosthesis.

PMID- 9033762
TI  - [Problems posed by spinal anesthesia in a patient with Gelineau disease].
AB  - A 44-year-old patient, with narcolepsy-cataplexy, underwent surgery for lumbar
      disk hernia under spinal anaesthesia. Our purpose was to prevent an interaction
      between the patient's disease and general anaesthetic agents with the risk of
      postoperative hypersomnia. During surgical procedure, two narcolepsy fits
      occurred, without clinical consequences. The postoperative course was uneventful.
      However, spinal anaesthesia cannot be considered as a technique of choice because
      of the risk of narcolepsy-cataplexy fits with loss of consciousness and atonia,
      during regional anaesthesia. General anaesthesia seems to be the best choice for
      these patients cholinergic agents and mainly the alpha1 adrenergic blocking drugs
      are contra-indicated as they increase the risk of narcolepsy-cataplexy fits.
      Anaesthetic sleep, narcolepsy, cataplexy and epilepsy are clinically rather
      similar. The EEG does not allow to differentiate between narcolepsy and
      anaesthetic-sleep, whereas cataplexy and epilepsy result in specific EEG
      patterns.

PMID- 9033763
TI  - [An unusual cause of oxygen desaturation: isorhythmic atrioventricular
      dissociation].
AB  - A 69-year-old man, with a history of angina pectoris treated with verapamil, was
      admitted in the intensive care unit after a right liver resection. On admission,
      the chest X ray and the arterial blood gases (PaO2/FlO2 = 320) were normal. There
      after, the patient exhibited brief decreases of SpO2 (at 82%) which were
      spontaneously reversible. The ECG showed an isorhythmic atrioventricular
      dissociation associated with SpO2 falls. The SpO2 returned to normal values when
      cardiac rhythm became sinusal again. This case shows that in case of an important
      and brief decrease in SpO2, unexplained by a respiratory cause, a decrease of
      arterial pressure due to rhythmic disease should be considered.

PMID- 9033764
TI  - [Acute interstitial nephritis. Role of ceftazidime].
AB  - A 22-year-old man treated with ceftazidime-amikacine for a Pseudomonas aeruginosa
      pneumonia, experienced two days later allergic symptoms, acute renal failure and
      urinary sediment abnormalities. The renal biopsy showed an acute interstitial
      nephritis. Basophils stimulation test was positive for ceftazidime. Early
      diagnosis and discontinuation of the suspected agent is essential to allow rapid
      and complete recovery of renal function.

PMID- 9033765
TI  - [Comparative measurement of pressure in the abdominal inferior vena cava and in
      the superior vena cava in adults].
AB  - Abdominal inferior vena cava pressure was compared to intrathoracic central
      venous pressure in 30 adults admitted in an intensive care unit following
      coronary artery bypass grafting. Mean pressures were obtained during controlled
      ventilation with a positive end expiratory pressure (PEEP) of zero and 10 cmH2O
      respectively, and during spontaneous breathing as well. Ninety measurements were
      obtained. Limits of agreement between intra-abdominal and intrathoracic cava
      pressures were below 2.5 mmHg in all cases. In this study, inferior vena cava
      pressure has predicted central venous pressure in adults during both controlled
      and spontaneous ventilation.

PMID- 9033766
TI  - [Wrong connection of a flexible medical air hose to a nitrous oxide outlet caused
      by a defective safety device].
AB  - When plugging the O2, N2O and air hoses into the corresponding wall sockets, the
      air hose was wrongly inserted into the N2O wall outlet. This was made possible
      because of faulty retaining clasps of the male coupler of the air probe. French
      "fail-safe" connections consist of a two-clasp male coupler for air, three clasps
      for O2 and four clasps for N2O hoses. Additionally the clasps of the air probe
      are broader then those of the N2O probe. However, the latter difference was lost
      due to wear. The incident was recognized without delay as the N2O hose could not
      be inserted into the air outlet. However, it could have remained unnoticed had
      there been two N2O wall outlets and could have resulted in severe adverse
      effects.

PMID- 9033767
TI  - [Numerical expression of results].

PMID- 9033768
TI  - [Statistics and presentation of results].

PMID- 9033769
TI  - [Bacterial meningitis after combined spinal and epidural anesthesia in
      obstetrics].

PMID- 9033770
TI  - [Problems caused by spinal sufentanil analgesia at the end of labor].

PMID- 9033771
TI  - [Analgesia after knee surgery].

PMID- 9033772
TI  - [Non electrical self-propelled syringes and transportation of patients].

PMID- 9033773
TI  - [Candida pyelonephritis].

PMID- 9033774
TI  - [Prolonged neuromuscular blockade caused by mivacurium].

PMID- 9033775
TI  - [Apropos of the use of Emla cream in ophthalmology].

PMID- 9033776
TI  - [Apropos of the refusal by Jehovah's witnesses of blood transfusion].

PMID- 9033777
TI  - [Repair of major tracheal tear following orotracheal intubation].

PMID- 9033778
TI  - [Tracheotomy with conscious sedation without initial intubation].

PMID- 9033779
TI  - [Apropos of transsectioned laryngeal mask].

PMID- 9033780
TI  - [Urapidil during surgery of pheochromocytoma: should begin in the preoperative
      period].

PMID- 9033781
TI  - [Hemodynamic management in the surgery of pheochromocytoma].

PMID- 9033782
TI  - [Impact of guidelines of the consensus conference on postoperative artificial
      nutrition].

PMID- 9033783
TI  - [Nutrition during the first months of life in children with intrauterine growth
      retardation].

PMID- 9033784
TI  - [Epidemiology of acute post-diarrhea hemolytic-uremic syndrome in children in 4
      French departments].

PMID- 9033785
TI  - [Fetal growth in premature infants in Haute-Normandie].
AB  - BACKGROUND: Fetal growth standards of preterm infants are different from one
      study to another, especially for extremely preterm babies. POPULATION AND
      METHODS: Between 1976 and 1990, a cross-sectional study of the resulting
      intrauterine growth of premature newborns from Haute-Normandie (France) was
      conducted by collecting data of the compulsory health certificate set up in the
      first week after birth. In spite of exclusions, curves for obstetrical terms
      ranging from 28 to 36 weeks of gestational age were settled. Equivalents of 8,042
      birth weights, 7,792 statures, 8,041 head circumferences and 6,737 ponderal index
      were used. RESULTS: Comparing our results with those published in the literature,
      we observed short differences for mean or middle values: from less than 170 to
      more than 180 g for weight, from less than 1 to more than 2.6 cm for stature and
      from less than 1 to more than 1.9 cm for head circumference. CONCLUSION: The
      selected normal lower threshold for each parameter and the varieties of fetal
      growth inadequacy are under discussion.

PMID- 9033786
TI  - [Androgen test: comparison of a low test and a high test in the development of
      the penis in male pseudohermaphroditism].
AB  - BACKGROUND: The androgen sensitivity test used in male pseudohermaphroditism for
      clinical assessment of the androgen sensitivity and prediction of penile
      development is an important element in choice of gender. However, there is a wide
      range of testosterone dosage and no standardized test. METHODS AND PATIENTS: Two
      doses (2.5 mg and 100 mg) of testosterone heptylate were used in six cases of
      male pseudohermaphrodism with sexual ambiguity and small penis (ages 6 to 18
      months). The clinical results were compared with those of the study of androgen
      receptors. RESULTS: In two cases, both low-dose and high-dose tests resulted in
      only minimal changes in the penis. In two cases, the low-dose test gave a good
      result which was confirmed by the high-dose test; on the other hand, in two
      cases, the low-dose test was considered to be negative whereas the high-dose test
      led to the development of a normal-sized penis. In all cases except one, there
      was good concordance between the results of study of androgen receptors and those
      of the clinical test. CONCLUSION: The high-dose androgen test is thus useful in
      both diagnosis and treatment and facilitates the gender assignment.

PMID- 9033787
TI  - [Evolution of the result of respiratory function studies in children with
      bronchopulmonary dysplasia].
AB  - BACKGROUND: Reports of short- and medium-term evolution of Lung Function Tests
      (LFT) in infants with bronchopulmonary dysplasia (BPD) are still scarce.
      POPULATION AND METHODS: The results of the first (before 3 months of corrected
      age) and the second (between 3 and 9 months of corrected age) LFT in 22 premature
      infants with BPD (gestational age 31 +/- 2.5 weeks; birth weight: 1570 +/- 440 g;
      duration of mechanical ventilation: 46 +/- 24 days, total duration of oxygen
      therapy: 88 +/- 47 days) were compared to those obtained in 27 normal infants for
      the first LEF and 10 normal infants for the second LFT, similar to the patients
      for birth weight and corporeal index (CI). RESULTS: In the first LFT, major
      abnormalities were an increased thoracic gaz volume (TGV) (16.5 +/- 42 vs 122 +/-
      24 mL; P < 0.001) and TGV CI ratio (1.25 +/- 0.31 vs 0.89 +/- 0.17 ml/kg/m2; P <
      0.0001) a decreased pulmonary compliance (2.49 +/- 1.46 vs 11.60 +/- 4.50
      mL/cmH2O; P < 0.0001) and specific pulmonary compliance (0.015 +/- 0.10 vs 0.100
      +/- 0.042 mL/cmH2O/mL de TGV; P < 0.0001), an increased total pulmonary
      resistance (20.4 +/- 12.1 vs 10.5 +/- 5.3 cmH2O/L/s; P < 0.001). In the second
      LFT, an increased TGV (235 +/- 62 vs 166 +/- 28 mL; P < 0.01) and TGV CI ratio
      (1.64 +/- 0.65 vs 0.98 +/- 0.11 ml/kg/m2; P < 0.05), a decreased pulmonary
      compliance (2.68 +/- 2.0 vs 15.2 +/- 5.7 mL/cmH2O; P < 0.0001) and specific
      pulmonary compliance (0.013 +/- 0.010 vs 0.106 +/- 0.050 mL/cmH2O/mL de TGV; P <
      0.0001), an increased total pulmonary resistance (17.1 +/- 9.6 vs 8.6 +/- 4.9
      cmH2O/L/s; P < 0.05) were noted when compared with the control group results.
      Major abnormalities of the blood gases were hypoxemia (63 +/- 10 vs 85 +/- 20
      mmHg; P < 0.05), hypercapnia (38.5 vs 31 +/- 4 mmHg; P < 0.0001) during the first
      LFT. Hypoxemia (77 +/- 14 vs 90 +/- 14 mmHg and hypercapnia (37 +/- 4 vs 29 +/- 5
      mmHg) continued in the second LFT. Thoracic distention and total pulmonary
      resistances in infants with BPD did not improve but their pulmonary compliance (P
      < 0.0001) and PaO2 (P < 0.01) between the first and second LFT did it. Infants
      who had been ventilated for a hyaline membrane disease (HMD) were more hypoxic on
      the second LFT (P < 0.05) than those who had been ventilated for other causes.
      Statistically significant relationships were found between thoracic distention
      and duration of positive inspiratory pressure (P < 0.05; r = 0.43), duration of
      positive expiratory pressure (P < 0.05, r = 0.45) total oxygen therapy duration;
      between total pulmonary resistance and duration of mechanical ventilation with
      high frequency (P < 0.05; r = 0.52); between hypoxemia and duration of oxygen
      therapy with FiO2 > or = 60% (P < 0.05; r = 0.54). CONCLUSIONS: This study shows
      prolonged clinical and functional abnormalities of the respiratory functions
      requiring longer follow-up.

PMID- 9033788
TI  - [Pneumococcal meningitis resistant to penicillin and nosocomial transmission in
      pediatric hospitals confirmed by genomic analysis].
AB  - BACKGROUND: Careful epidemiological studies and sophisticated diagnostic
      procedures are necessary to prove that bacterial infection is nosocomial in
      origin. DNA finger printing method can be useful with this aim in view. CASE
      REPORTS: A 11 month-old girl suffered from a febrile pneumonia. She developed
      acute meningitis 15 days later; culture of CSF grew Streptococcus pneumoniae,
      serotype 23 F, resistant to beta-lactamines, erythromycin and cotrimoxazole. She
      died 24 hours later. Five days after this death, a 5 month-old infant
      hospitalized in the next bed developed an acute pulmonary infection due to the
      same strain with the same bacterial characteristics; this patient was cured with
      cefotaxime plus vancomycin and gentamicin. Randomly amplified polymorphic DNA
      analysis showed an identical profile of both strains. CONCLUSION: This is the
      first case of meningitis due to penicillin-resistant Streptococcus pneumoniae
      (PRSP) associated with nosocomial spread between two children in adjacent beds.
      This case suggests that it is necessary to isolate patients with PRSP infection
      during hospitalization.

PMID- 9033789
TI  - [Aniridia and Wilms tumor: 2 cases of fetal rhabdomyomatous nephroblastoma].
AB  - BACKGROUND: Wilms tumor is associated in 7 to 10% of patients with congenital
      abnormalities. Among those, aniridia is the most constant feature of the WAGR
      syndrome that includes, in one third of cases. Wilms tumor. We report two cases
      of aniridia associated with fetal rhabdomyomatous nephroblastoma. CASE REPORTS:
      Case 1. A one-year old girl with congenital aniridia was admitted for macroscopic
      hematuria. Abnormal ultrasonography and tomodensitometry revealed a large,
      bilateral, kidney tumor. The patient was given actinomycin and vincristine,
      without efficacy. Bilateral tumorectomy was performed 6 months later and the
      histological study showed a fetal rhabdomyomatous nephroblastoma. This patient is
      in remission at the age of 5. Case 2. A boy, also with congenital aniridia,
      presented with macroscopic hematuria at the age of 2 years revealing a
      nephroblastoma located on his right kidney. Preoperative chemotherapy remained
      uneffective and the nephrectomy performed 1 month later permitted the diagnosis
      of fetal rhabdomyomatous nephroblastoma. The patient is well 4 years later.
      CONCLUSION: Both cases of fetal rhabdomyomatous nephroblastoma, a histological
      variant of Wilms tumor, seem to be the first reported in the WAGR syndrome.

PMID- 9033790
TI  - [Liver transplantation in an adolescent with cystic fibrosis].
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is an effective treatment for
      patients with cystic fibrosis end stage liver disease, especially those with only
      mild pulmonary involvement. Long-term follow-up in such transplanted patients is
      still lacking. CASE REPORT: A 15-year-old girl with cystic fibrosis received an
      OLT because of severe decompensated cirrhosis. She had been colonized by
      Pseudomonas aeruginosa for 3 years and had pancreatic insufficiency; she also had
      mild glucose intolerance. Postoperatively she developed diabetes mellitus
      requiring insulin therapy for 9 months. Oral cyclosporin was poorly absorbed so
      that she was given a new emulsion of cyclosporin (Neoral) that was better
      absorbed. A rapid pubertal catch-up was obtained but the patient remained
      colonized by Pseudomonas aeruginosa. CONCLUSION: This 3-year postoperative follow
      up confirms that OLT can represent a good alternative in those patients with
      severe liver disease and mild pulmonary involvement.

PMID- 9033791
TI  - [Fatal double tracheo-esophageal vascular compression and neurofibromatosis].
AB  - BACKGROUND: Vascular rings are a classical cause of tracheal and esophagus
      compression. We report the case of such an abnormality in an infant with
      neurofibromatosis. CASE REPORT: A 1 week-old male infant with a familial
      neurofibromatosis presented a stridor with severe respiratory distress. A
      vascular ring was demonstrated and operated on. The stridor persisted after
      surgery. A postoperative oesophagogram and tracheobronchoscopy showed an
      irregular compression of the oesophageal lumen, thought to be due to a residual
      extrinsic compression. Because the postoperative echocardiogram showed an
      extensive tumoral infiltration of both auricles, it was decided to not operate
      again the child. The postmortem examination revealed a disseminated
      neurofibromatosis infiltrating trachea, bronchi and also the wall of esophagus.
      CONCLUSION: Persisting stridor and oesotracheal compression postoperatively
      requires search for another cause. Association of vascular ring and
      neurofibromatosis is probably not fortuitous.

PMID- 9033792
TI  - [Association of mixed gonadal dysgenesis and non-classic 21-hydroxylase
      deficiency].
AB  - BACKGROUND: The rare association of mixed gonadal dysgenesis and non classical
      congenital hyperplasia by 21-hydroxylase deficiency poses the problem of their
      respective responsibility in the development of sexual ambiguity. CASE REPORT: In
      a newborn with ambiguous genitalia, blood 17-OH progesterone was moderately
      elevated (3.9 to 14.1 ng/mL) leading to the diagnosis of non-classical 21
      hydroxylase deficiency, Molecular studies later confirmed this diagnosis.
      However, the presence of a palpable gonad and the karyotype (45 X/46 XY
      mosaicism) indicated a mixed gonadal dysgenesis as the cause of sexual ambiguity.
      Histological examination revealed the presence of a testis and a streak gonad.
      CONCLUSION: This observation emphasizes the need for a complete clinical and
      biological analysis in all newborns with sexual ambiguity.

PMID- 9033793
TI  - [Kangaroo method and care].
AB  - The kangaroo-mother method was initiated by colombian pediatricians in 1979. The
      method is based on a permanent skin to skin contact of low birth weight infants
      with their mother. It has spread out in many developing countries as an
      alternative cheap method for the care of low birth weight infants with several
      advantages: temperature regulation, prolonged breast-feeding, promotion of mother
      infant interaction, decreased mortality. The kangaroo method has been adapted in
      European countries as kangaroo care that consists in daily mother-infant skin to
      skin contact during few hours. Introducing the incubator in the mother's room is
      an other derivative of the method which allows prolonged early contact of the
      mother with her infant. A major interest of these methods is that they favour
      parent-infant interaction; however this requires qualified and devoted staffs.

PMID- 9033794
TI  - [Is Ambu ventilation of newborn infants a simple question of finger-touch?].
AB  - Insufflation pressures were measured during manual ventilation using a neonatal
      rebreathing bag (Ambu on a manikin. Maximal insufflation pressures were greater
      than that published or given by the manufacturer, theoretically limited to 30 cm
      of water at open valve, and that whatever the number of fingers used for the
      compression of the bag. These results indicate that Ambu ventilation, often
      mandatory for newborn resuscitation, does not simply rely upon the finger-touch
      of the operator and that it always has a risk of baro and/or volotraumatism.

PMID- 9033795
TI  - [Plasticity of the myocardium in pediatric cardiology].
AB  - The phenotypic adaptation of the myocardium to mechanical overload is a well
      known concept. The changes that occur into the myocardial structure in heart
      failure lead to new therapeutical approaches, particularly the use of ACE
      inhibitors in the treatment of dilated cardiomyopathies in order to prevent
      myocardial remodeling. In the hypoplastic left heart syndrome or in pulmonary
      atresia-intact septum, the pathogenetic process is supposed to be abnormal intra
      cardiac blood flow during fetal life inducing abnormal cardiac remodeling. When
      the left ventricle ejects into the pulmonary circulation (double discordance,
      atrial repair of transposition of the great arteries), the surgical repair that
      consists to replace the left ventricule in the systemic circuit is based on the
      concept of ventricular remodeling and plasticity.

PMID- 9033796
TI  - [Radiological case of the month. Subacute osteomyelitis of the ankle].

PMID- 9033797
TI  - [Association of Crouzon syndrome and Arnold-Chiari deformity].

PMID- 9033798
TI  - [Frequency of the main mutation (delta F508) of cystic fibrosis in France: new
      results about 1656 unrelated families].

PMID- 9033799
TI  - [Familial rheumatoid purpura].

PMID- 9033800
TI  - [Multicystic kidney dysplasia and malignant degeneration].

PMID- 9033801
TI  - [Physicians with foreign diplomas and pediatric care in Ile de France].

PMID- 9033802
TI  - Paulo Sawaya (1903-1995)

PMID- 9033803
TI  - The molecular and cellular correlates of immunological phenomena. Contrasting two
      explanatory pathways.

PMID- 9033804
TI  - The "impact factor" as a criterion for the quality of scientific production is a
      relative, not absolute, measure.

PMID- 9033805
TI  - Modern role of pharmacology in health sciences: assessing and accessing
      traditional medicines.

PMID- 9033806
TI  - Intracellular targets for nitric oxide toxicity to pancreatic beta-cells.
AB  - The radical nitric oxide (NO) may be a mediator of pancreatic beta-cell damage in
      early insulin-dependent diabetes mellitus (IDDM). Under the stimulus of
      cytokines, invading macrophages and the beta-cell themselves may produce large
      amounts of NO, leading to beta-cell dysfunction and death. It still remains to be
      determined which are the intracellular targets for NO-induced damage. Available
      data from rat islets indicate that the radical inactivates the mitochondrial
      enzyme aconitase, impairing substrate oxidation and ATP production. Ionic
      channels and complexes I and II of the mitochondrial electron transport chain are
      two other possible targets for NO effects which may impair insulin secretion. NO
      also leads to nuclear DNA damage in both rat and human pancreatic beta-cells, as
      evaluated by the 'comet assay'. The effects of NO at the DNA level are complex,
      and involve formation of N-nitrosoamines, deamination of purines and pyrimidines,
      or damage induced by peroxynitrite. Besides inducing over DNA damage. NO may also
      inactivate DNA repair/replication enzymes. The outcome of NO-induced beta-cell
      DNA damage can be cell death by apoptosis or, in some cases, necrosis. Upon cell
      damage beta-cells trigger cell repair mechanisms. This seems also to be the case
      following NO exposure, and insulin-producing cells are able to regain their
      function following treatment with non-lethal concentrations of NO. A better
      understanding of the mechanisms involved in NO-induced beta-cell damage and
      repair may be instrumental in developing new strategies for IDDM prevention.

PMID- 9033807
TI  - Morphogenesis of the epithelial cell transporting phenotype: synthesis and
      distribution of ion channels.
AB  - The exchange of substances between higher organisms and the environment takes
      place across epithelia consisting of one or more cell layers. To perform this
      function, epithelial cells have two basic differentiated properties: 1) they form
      tight junctions (TJs) that seal the extracellular space, and 2) they are
      polarized into an apical and a basolateral domain, with entirely different
      structural, biochemical and physiological properties. Our understanding of the
      mechanisms involved in the expression of these properties has been greatly
      enhanced by the availability of epithelial cell lines that form TJs and polarize
      in vitro under conditions suitable for experimental control. In this article we
      summarize our studies on the synthesis and polarized expression of ion channels
      in epithelial cells. MDCK cells have four types of K+ channels in the apical
      domain, and a fifth one in the basolateral domain. The basolateral side also has
      a population of CI- channels. Each type of channel is absolutely polarized.
      Harvesting with trypsin-EDTA reduces the area of the plasma membrane by 50% and
      the channel population by 90%. Upon plating, these channels are recovered within
      a few hours. We describe here the main extracellular and intracellular mechanisms
      involved in these phenomena.

PMID- 9033808
TI  - Comparison of the biochemical properties, regulation and function of ATP
      diphosphohydrolase from human placenta and rat kidney.
AB  - ATP-diphosphohydrolase (apyrase. EC 3.6.1.5) has both ATPase and ADPase activity
      that are stimulated by bivalent metals, with Ca2+ being the most effective. The
      possible physiological function of this enzyme, associated with placental and
      renal microvilli, is related to the extracellular metabolism of nucleotides. A
      comparison of the biochemical properties of human placenta and rat kidney apyrase
      is presented, showing similarities in Mr. bivalent metal stimulation, nucleotide
      nonspecificity, insensitivity towards specific ATPase inhibitors, and lack of
      essential sulfhydryl and aliphatic hydroxyl groups. We describe the treatment of
      membrane preparations from both tissues with different detergents and the
      isoelectric focusing of the solubilized proteins to partially purify apyrase. An
      ectoenzyme localization is assigned both in microvillus membranes and in the
      vasculature on the basis of organ perfusion experiments with nucleotides in the
      presence of antibodies. Placental and kidney microvillus membranes inhibited ADP
      induced platelet aggregation, in agreement with an extracellular role. Initial
      studies on enzyme regulation suggested the existence of at least two types of
      modulatory proteins: an activating protein in the cytosol of both tissues, and an
      inhibitory protein associated with placental microsomes. Possible hormonal
      regulation was investigated in kidneys using in vivo estradiol treatment, but
      only slight changes in total apyrase activity were observed.

PMID- 9033809
TI  - Serine/threonine protein phosphatases and a protein phosphatase 1 inhibitor from
      Neurospora crassa.
AB  - The major spontaneously active serine/threonine (Ser/Thr) protein phosphatase
      activities in N. crassa wild type (FGSC 424) were type-1 (PP1), type-2A (PP2A)
      and type-2C (PP2C). PP1 and PP2C predominantly dephosphorylated phosphorylase a
      and casein, respectively. PP2A acted on both substrates, but was two-fold more
      active against casein. PP1 activity was inhibited by protamine, heparin, okadaic
      acid (IC50 50 nM) and mammalian inhibitor-1 (IC50 2 nM). On the other hand. PP2A
      activity was inhibited by much lower concentrations of okadaic acid (IC50 0.2 nM)
      and also by protamine, but not by heparin or inhibitor-1. About 80% of total PP1
      activity was associated with the particulate fraction and could be partially
      extracted with 0.5 M NaCl. Seventy and ninety percent of PP2A and PP2C
      activities, respectively, were found in the soluble fraction. In addition we have
      partially purified an acid and thermostable PP1 inhibitor which effectively
      inhibits both N. crassa and mammalian PP1.

PMID- 9033810
TI  - Slow coronary run-off in patients with angina pectoris: clinical significance and
      thallium-201 scintigraphic study.
AB  - To determine whether or not slow coronary flow (SF) depends on hemodynamic
      variables, we studied 17 patients (15 men, mean age = 47.8 years) with SF at
      coronariography. Exercise thallium-201 myocardial scintigraphy revealed perfusion
      abnormalities in 13 (76.4%) patients. We then selected 89 individuals submitted
      to cinecoronariography for comparison: 15 were normal and 74 had heart disease.
      The coronary flow velocity was evaluated by the number of heart beats (HB) needed
      for coronary artery dye filling. The patients in the SF group had normal
      hemodynamic variables which were significantly different from those of patients
      with heart disease (P = 0.001). Patients with heart disease needed no more than 4
      HB to fill their arteries, in contrast to 6.88 +/- 1.68 (5 to 11) in the SF group
      (P < 0.0001). Thus, in our patients with myocardial scintigraphy suggesting
      ischemia, SF was found to be an event which did not depend on hemodynamic
      factors.

PMID- 9033811
TI  - Suppressor activity in Leishmania donovani-infected hamster serum: reversion by
      delipidated bovine serum albumin and role in cell cycle events.
AB  - Visceral leishmaniasis, caused by Leishmania donovani, is a chronic disease with
      a high mortality rate. This protozoan induces a serious dysfunction of the immune
      system characterized by suppression of the cellular response to parasite
      antigens. We provide evidence for the involvement of lipids in the immunological
      alterations of experimental leishmaniasis. Sera obtained from 60-day-infected
      hamsters present increased triglyceride levels. Inhibition of cell proliferation
      was observed when splenocytes from normal hamsters were stimulated with
      concanavalin A in the presence of 3% infected hamster serum (IHS) (Control 50 +/-
      3 (x10(3)) cpm; IHS 5 +/- 1 (x10(3)) cpm). This inhibition was reversed by the
      addition of 5 mg/ml of delipidated bovine serum albumin (BSA) to the cultures
      (Control 65 +/- 1 (x10(3)) cpm; IHS 75 +/- 3 (x10(3)) cpm). The inhibitory effect
      of IHS was demonstrable only when added to the culture simultaneously with the
      mitogen. This effect was not as intense on fresh, pre-activated cells or on the
      CTLL-2 cells. This cell line stimulated by IL-2 in the presence of IHS is only
      marginally inhibited (about 20% inhibition). The suppressor effect on CTLL-2 was
      not reversed by the addition of increasing doses of IL-2 (up to 100 U/ml) to
      cultures. The inhibition of the proliferative response of the CTLL-2 cells caused
      by IHS was also reversed by the addition of delipidated BSA. Our data suggest a
      role for fatty acids in the infected hamster serum-induced suppression of normal
      or L. donovani-infected cell proliferation.

PMID- 9033812
TI  - Improvement of the slide hemagglutination test for rapid Chagas' disease
      screening in epidemiological surveys.
AB  - A slide hemagglutination test, here called SHAT, which is practical and
      economical for seroepidemiological surveys was standardized. This is an improved
      modification of the rapid hemagglutination test (RHA) which utilizes a short
      lived reagent prepared with fresh blood cells. The reagent and conditions of the
      test were considerably modified and, most importantly, an alkaline-solubilized
      Trypanosoma cruzi epimastigote antigen reagent is proposed. The stability of the
      SHAT reagent was at least one year at 4 degrees C, in an appropriate liquid
      suspension. The SHAT was applied to 71 serum samples from patients with Chagas'
      disease and from 235 clinically healthy blood donors. Sensitivity, specificity
      and positive and negative predictive values for the selected cutoff titer
      corresponding to 1:4 dilution were 0.972 (0.903-0.992), 0.983 (0.957-0.993),
      0.945 (0.867-0.979) and 0.991 (0.969-0.998), respectively. These values were
      comparable to those found for the RHA, immunofluorescence (IFT), indirect
      hemagglutination (IHAT) and complement fixation (CFT) tests. These data suggest
      that the SHAT should be useful for seroepidemiological surveys conducted at
      public health laboratories in developing countries.

PMID- 9033813
TI  - Crotoxin-induced behavioral effects in rats.
AB  - Crotoxin is the major component of Crotalus durissus terrificus venom. In view of
      the presence of high-affinity specific binding sites for crotoxin in the brain,
      the objective of this work was to investigate whether crotoxin induces behavioral
      effects in the open-field and hole-board tests. Adult male Wistar rats (180-220
      g) treated with crotoxin, 100, 250 and 500 micrograms/kg, ip, administered 2 h
      before the test, presented statistically significant behavioral alterations
      (ANOVA for one-way classification complemented with Dunnet test, P < 0.05). In
      the open-field test, 250 and 500 micrograms/kg of crotoxin increased freezing
      (from 3.22 sec to 10.75 sec and 11.2 sec) and grooming (from 13.44 sec to 22.75
      sec and 21.22 sec) and decreased ambulation (from 64.8 to 39.38 and 45.8). The
      dose of 500 micrograms/kg also decreased rearing (from 24.9 to 17.5). In the hole
      board test, 500 micrograms/kg of crotoxin decreased head-dip count (from 6.33 to
      4.00). All the crotoxin-induced behavioral effects were antagonized by an
      anxiolytic dose of diazepam (1.5 mg/kg, ip. 30 min before the tests). These
      results show that crotoxin reduced open-field activity and exploratory behavior
      as well. We suggest that these effects express an increased emotional state
      induced by this toxin.

PMID- 9033814
TI  - Effect of an aerobic exercise program on blood pressure and catecholamines in
      normotensive and hypertensive subjects.
AB  - Interrelations between physical exercise, monoamines and hypertension are
      postulated by various investigators. The purpose of the present study was to
      determine and compare catecholamine levels at rest and after a 12-week aerobic
      exercise program in 11 sedentary normotensive (N) and 8 hypertensive (H) men.
      Plasma catecholamines were determined by high performance liquid chromatography
      with electrochemical detection. A significant post-exercise increase in plasma
      noradrenaline was observed in the N and H groups (P < 0.01) both before and after
      the aerobic exercise program. The hypertensive group showed a significant
      reduction of the sum of 7 skinfold thickness scores after the aerobic exercise
      program (from 178.7 +/- 65.6 to 144.0 +/- 47.4 mm) although no significant
      difference was observed when the body mass index was compared. A significant
      reduction in diastolic blood pressure at rest was observed in the H group after
      the aerobic exercise program (from 99.2 +/- 2.0 to 85.0 +/- 5.5). There were no
      significant differences in catecholamine concentrations between groups before and
      after the 12-week aerobic exercise program at rest and post-exercise. These data
      show a relationship between physical exercise and hypertension that was not
      related to changes in plasma catecholamine levels.

PMID- 9033815
TI  - D-fenfluramine selectively releases 5-HT from dorsal raphe terminals.
AB  - The aim of this study was to investigate whether D-fenfluramine (FEN) releases 5
      hydroxytryptamine (5-HT) selectively from dorsal raphe (DR) terminals. Male
      Wistar rats, 180-200 g, were implanted with microdialysis probes ir the amygdala
      (Am; N = 5) and dorsal hippocampus (DH; N = 6) and 5-HT levels were measured by
      electrochemical detection. Under basal conditions, 5-HT levels were approximately
      50 and 230 fmol per 30 min sample, in the Am and DH, respectively. FEN (10 mg/kg.
      ip) produced a 3-4-fold increase in 5-HT release in the Am, but not in the DH.
      Since the Am is mainly innervated by DR fibers while the DH receives 5-HT input
      chiefly from the median raphe (MR), the present results support the view that FEN
      selectively releases 5-HT from DR terminals.

PMID- 9033816
TI  - Anti-inflammatory and analgesic activity of a water-soluble fraction from shark
      cartilage.
AB  - The anti-inflammatory and analgesic activities of a water-soluble fraction (WSF),
      extracted with 0.1 M ammonium bicarbonate, pH 8.0, from shark cartilage were
      studied in several experimental models. Orally administered WSF (10 mg/kg) caused
      25.7 and 23.6% inhibition of the paw edema produced in female Wistar rats (200
      250 g) by carrageenan and dextran, respectively, after 3 h, as compared to
      controls. WSF administered orally had no effect on acetic acid-induced writhings
      in male Swiss mice (25-30 g) at the dose of 0.01 mg/kg but caused 52.8 and 61.4%
      inhibition at the doses of 0.1 and 0.5 mg/kg, respectively, compared to controls
      (No. of writhings/20 min, means +/- SEM: treated groups = 18.6 +/- 2.5, N = 12
      and 15.2 +/- 1.4, N = 12, respectively; controls = 39.3 +/- 1.3, N = 77). In the
      formalin test (male Swiss mice, 25-30 g), orally administered WSF (0.5 and 1
      mg/kg) caused 12.0 and 46.6% inhibition of licking time, respectively, only in
      the 2nd phase (inflammatory) of the test (licking time, means +/- SEM: treated
      group = 18.3 +/- 4.4 sec, N = 7 and 11.1 +/- 3.4 sec, N = 13; controls = 20.8 +/-
      2.4 sec, N = 44). The results suggest that a molecule of a protein nature in
      shark cartilage is probably responsible for the effects observed.

PMID- 9033817
TI  - Antiviral activity of crude extracts of Guarea guidona.
AB  - Crude extracts of leaves and fruits of Guarea guidona were tested for antiviral
      activity against pseudorabies virus and foot-and-mouth disease virus in the IB-RS
      2 pig cell line and against bovine herpesvirus-1 (BHV-1) in the GBK bovine cell
      line. The highest nontoxic doses of extracts from fruits and leaves were 125
      micrograms/ml and 500 micrograms/ml. respectively. Crude extracts presented
      antiviral activity against pseudorabies virus with a decrease in virus titer of
      3.0 log units at 500 micrograms/ml. Virucidal activity was not observed at 62.5
      micrograms/ml. Preformed cell monolayers showed no cytotoxic effect after 48 h in
      the presence of 500 micrograms/ml in pig cells. G. guidona leaves did not induce
      an antiviral state but exhibited antiviral effects during the early stage of
      viral infection.

PMID- 9033818
TI  - Ethanol elimination by rats as a function of reproductive state, gender and
      nutritional status.
AB  - Alcohol elimination was studied in rats of different ages, reproductive states
      and nutritional deprivation, with the following results: 1) blood levels of
      ethanol 180 min after a single dose of 1.5 g/kg, ip were significantly higher in
      adult male (74 days old, N = 5) than in young male rats (34 days old, N = 5):
      92.4 +/- 8.4 vs 6.8 +/- 3.4 mg/100 ml, means +/- SD, respectively; 2) when male
      rats were given a low protein diet for 48 h, blood ethanol levels after a single
      dose were significantly increased in young males (38.6 +/- 14.6 mg/100 ml) but no
      effect after a single dose was found in the same animals at an older age (93.2 +/
      5.0 mg/100 ml); 3) blood levels in female rats were higher than in young males
      both in the virgin and pregnant states, but during lactation a significant drop
      in blood levels of ethanol was observed. Blood levels of ethanol (mg/100 ml) 180
      min after a single dose of 1.5 g/kg, ip, in females, were: virgin (N = 6): 44.9
      +/- 16.1, pregnant (N = 5): 40.0 +/- 10.4, lactant (N = 5) 8.8 +/- 5.8. This
      difference between virgin and pregnant and lactant rats was not related to
      changes in ADH activity which did not differ between groups. The present study
      indicates that in male rats the effect of a short-term protein deprivation on
      ethanol elimination is dependent on the age of the animal. In females,
      reproductive state is an important factor in determining ethanol elimination.

PMID- 9033819
TI  - Plasma steroid and corticosteroid levels in female pacu Piaractus mesopotamicus,
      Teleostei-Characidae.
AB  - We report the plasma levels of estradiol-17 beta (E2), testosterone (T), 17 alpha
      20 beta-dihydroxy-4-pregnen-3-one (17-20P), and cortisol (F) in female pacu
      during the reproductive cycle (N = 44) and in females induced to ovulate with an
      analogue of luteinizing hormone releasing hormone (LHRHa; 10 micrograms/kg) (N =
      24). The plasma hormone levels were determined by validated radioimmunoassays.
      Females sampled during the reproductive cycle were grouped into 4 gonadal stages:
      resting, early maturation, advanced maturation and regression. The calculated
      gonadosomatic index varied from 0.5 +/- 0.1% in resting stage to 8.1 +/- 0.6% in
      advanced maturation stage. The E2 and T values were highest during the early
      maturation stage (E2 = 2172 +/- 7.1 pg/ml; T = 412 +/- 58 pg/ml) and the F values
      were highest during the advanced maturation stage (132 +/- 5 ng/ml). Females
      induced to ovulate by LHRHa injection were sampled at 0.6, and 12 h after
      injection of LHRHa. Two additional groups were sampled at ovulation and 24 h
      after ovulation. The E2 values were highest at 6 h (2917 +/- 65 pg/ml). The T and
      F values were highest at ovulation (T = 3498 +/- 77 pg/ml; F = 387 +/- 16 ng/ml)
      and 17-20P was detected only at ovulation (2163 +/- 80 pg/ml).

PMID- 9033820
TI  - Effect of congenital hypothyroidism on cell density in the ganglion cell layer of
      the rat retina.
AB  - The effect of congenital hypothyroidism on the visual system of Wistar rats was
      studied by determining neuron density in the retinal ganglion cell layer. Retinae
      of adult rats from mothers treated with propylthiouracil, 50 mg/day, starting on
      the 15th day of pregnancy (PTU group), and of adult rats from untreated mothers
      (control group) were examined. Retinae were prepared, and the neurons in the
      nasotemporal region located above the optic disc were counted. Hypothyroid rats
      showed a significant reduction in the retinal area (about 6.8%), when compared to
      controls. The cell density in the retinal ganglion cell layer was significantly
      decreased in 6 PTU-treated compared to 5 control retinae in total (2,793 +/- 330
      vs 3,704 +/- 662 neurons/mm2), nasal (3,031 +/- 580 vs 3,853 +/- 699 neurons/mm2)
      and temporal (2,555 +/- 155 vs 3,555 +/- 827 neurons/mm2) regions. These
      alterations in a region considered to be one of the most specialized in the
      visual process suggest a structural deficiency induced by congenital
      hypothyroidism, with a possible decrease in the visual acuity of the rat.

PMID- 9033821
TI  - A crude extract of Stevia rebaudiana increases the renal plasma flow of normal
      and hypertensive rats.
AB  - The effect of S. rebaudiana extract on renal function was evaluated in
      normotensive and in experimental renal hypertensive rats (GII) using clearance
      techniques. Experiments were performed on male Wistar rats weighing 300-330 g (10
      animals per group). Goldblatt GII experimental hypertension was induced by
      placing a silver clip with an internal gap of 0.25 mm around the left renal
      artery under ether anesthesia. The contralateral kidney was left untouched.
      Stevia was administered 10-12 weeks after clipping. Oral-administration of Stevia
      extract, corresponding to 2.67 g dry leaves/day for 30 days, resulted in a
      significant decrease in mean arterial pressure in both the normo-(N) and
      hypertensive rats (H) (N rats: 113 +/- 3.0 mmHg in the control (C) group vs 69.5
      +/- 4.0 mmHg in the Stevia (S) group; H rats: 155 +/- 3.0 mmHg in C vs 108 +/-
      4.0 mmHg in S; P < 0.05). Glomerular filtration rate was constant in the N rats
      and increased significantly in the H rats after Stevia treatment 16.47 +/- 1.29
      vs 14.2 +/- 1.33 ml min-1 kg-1 in the C and S groups, respectively, P < 0.05).
      Normo- and hypertensive rats presented an increase in renal plasma flow following
      oral Stevia administration (N rats: 16.4 +/- 3.10 ml min-1 kg-1 in the C group vs
      33.3 +/- 3.20 ml min-1 kg-1 in the S group. P < 0.05; H rats: 19.30 +/- 2.45 ml
      min-1 kg-1 in the C group vs 37.0 +/- 3.93 ml min-1 kg-1 in the S group, P <
      0.05). Stevia administration provoked an increase in urinary flow in both N and H
      animals (1.37 +/- 0.08% vs 2.32 +/- 0.11%, P < 0.05 and 1.47 +/- 0.07% vs 2.96 +/
      0.13%, P < 0.05 in N and H rats, respectively). Sodium excretion increased in N
      and H animals after Stevia treatment (N rats: 0.61 +/- 0.07% in the C group vs
      1.55 +/- 0.20% in the S group, P < 0.05; H rats: 0.70 +/- 0.10% in the C group vs
      2.22 +/- 0.45% in the S group, P < 0.05). These results are consistent with
      impairment of a renal autoregulation mechanism in this hypertensive model after
      Stevia administration. In conclusion, it was shown that Stevia extract, at doses
      higher than used for sweetening purposes, is a vasodilator agent in normo- and
      hypertensive animals.

PMID- 9033822
TI  - Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing
      hormone/thyrotropin (TRH/TSH) secretion in rats.
AB  - In order to investigate the role of serotonin in the regulation of thyrotropin
      (TSH) secretion, control and propylthiouracil (PTU)-treated male Wistar rats
      weighing approximately 250 g were subjected to ip injections of methysergide
      (MET, 10 micrograms/100 g body weight), a serotonergic receptor blocker, and
      killed 60 min later by decapitation. Serum and pituitary concentrations of TSH
      were measured by radioimmunoassay. An addition, the pituitary release of TSH was
      estimated in an in vitro system in which pituitary glands were incubated with
      hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 +/-
      18.55 vs 199.30 +/- 31.47 micrograms/mg, N = 20), and serum (1.95 +/- 0.92 vs
      4.26 +/- 1.40 ng/ml, N = 20) TSH concentration (P < 0.001) and also to a
      decreased in vitro pituitary response to control hypothalamic extracts (55 +/- 8
      vs 78 +/- 7%, N = 5, P < 0.005). In addition, hypothalamic extracts of MET
      treated rats significantly facilitated in vitro pituitary TSH secretion,
      suggesting an enhanced hypothalamic thyrotropin releasing hormone (TRH) activity
      (347 +/- 62 vs 78 +/- 7%, N = 5, P < 0.001). These results suggest that serotonin
      participates in the physiological control of TRH/TSH secretion, probably by
      increasing TRH production/secretion, and/or by facilitating the pituitary TSH
      response to TRH.

PMID- 9033823
TI  - [Pneumocephalus: a prognostic factor in head injuries. Results of a retrospective
      study of 167 patients].
AB  - Presence of air within the cranial cavity has been described by several authors.
      Little attention has been paid to its significance. The goal of this study was to
      analyse the clinical characteristics and the evolution of patients with
      pneumocephalus. We reviewed the brain computed tomography scans of 167
      consecutive head injury patients who were hospitalized between January 1992 and
      December 1993. This retrospective study revealed intracranial air in 33 cases
      (19%). The analysis of clinical characteristics showed that in the initial period
      the neurologic status was better in patients with pneumocephalus. However, 48
      hours later, the proportion of patients presenting a deep coma increased We
      conclude that pneumocephalus is a significant risk factor in head injury
      patients.

PMID- 9033824
TI  - [Postoperative analgesia by auriculotherapy during laparoscopic cholecystectomy].
AB  - Auriculotherapy based on traditional Chinese cartography can be used for pain
      relief after laparoscopic cholecystectomy. It consists of palpating and pricking
      some well defined ear points corresponding to the surgical site. Relief was
      quickly obtained and compares favourably with minor parenteral analgesics.

PMID- 9033825
TI  - [Value of ilio-hypogastric block in appendectomy in children].
AB  - This prospective study aimed to evaluate the efficiency of ilio-hypogastric nerve
      block for control of post appendicectomy pain in children. Forty-two children
      aged 3-15 years scheduled for appendicectomy were anaesthetized in the same way.
      After randomization, a preoperative ilio-hypogastric nerve block was performed in
      21 patients. Twenty one were not blocked. The postoperative pain assessment
      showed a better analgesia in the blocked children group. Analgics were required
      less in group. Five inefficient blocks were recorded. No complications were
      noted. Ilio-hypogastric block was found to be safe and efficient for control of
      post-appendicectomy pain in most children.

PMID- 9033826
TI  - [Protective efficacy of 3 anesthetic methods with reference to surgical stress in
      children].
AB  - Hormonal-metabolic stress responses have beyond doubt an effect on
      morbidity/mortality related to surgery. The present study med to determine which
      anaesthetic technique could afford the best protection in children, through
      analysis of the perioperative cortisol, prolactin and beta-endorphin plasma
      levels. Thirty-six young patients 3-10 years old, ASA I-II, scheduled for
      hypospadias or vesicoureteral reflux surgery of a duration > 60 min, were
      randomized into three groups (n = 12). Children of group I were given initially
      propofol and fentanyl then isoflurane 1%; group 2 received TIVA with propofol and
      fentanyl, group 3 received initially propofol then an epidural lumbar block with
      bupivacaine 0.25% (single shot) and continuous propofol i.v. infusion. Cortisol,
      prolactin and beta-endorphin levels increased significantly in group 1 only. No
      significant differences were observed between group 2 and 3. Early postoperative
      analgesia was better in group 3. These data suggest that TIVA and particularly
      epidural block could afford a better protection against the surgical stress in
      children submitted to subumbilical operations.

PMID- 9033827
TI  - [Erythrocytapheresis a few weeks before surgery: an alternative to erythropoietin
      treatment in programmed autologous transfusion].
AB  - The usual methods like hypotension, isovolaemic haemodilution, autologous
      transfusion and peri-operative blood salvage may significantly reduce the need
      for homologous blood transfusion in haemorrhagic surgery and also the risk of
      transmitting infectious agents. Erythropoietin (EPO) is now available and is used
      to stimulate red cell regeneration in pre-operative autologous blood donation. In
      acute anaemia, many studies have shown that the stimulation of endogenous
      erythropoietin production could be very high and accelerate red blood cell
      production. Taking higher quantities of blood than usual induces a secretion of
      endogenous erythropoietin, and could be an alternative for the utilization of
      exogenous EPO in autologous blood donation.

PMID- 9033828
TI  - [Acute fetal distress. The anesthesiologist's point of view].
AB  - Foetal distress is a non-specific and imprecise diagnose sometimes associated
      with surgical delivery of a normal newborn. As this type of delivery is usually
      considered urgent, emergent anaesthesia is required. General anaesthesia is
      usually chosen in these cases because it is the quickest anaesthetic technique
      and because of fears concerning the haemodynamic consequences of regional
      techniques. Maternal risks of general anaesthesia which is the leading cause of
      anaesthesia-related maternal mortality (difficult intubation and Mendelson's
      syndrome) but also neonatal consequences (increased need for neonatal
      resuscitation) have challenged this policy. Indeed, spinal anaesthesia and
      extension of a pre-existing epidural analgesia are more and more used during
      emergency Caesarean section. A better evaluation of the patient's problems based
      upon a pre-anaesthetic outpatient visit during the last trimester of pregnancy
      allows a more rational approach to meet the patient's requirements should an
      emergency. Caesarean section be necessary. For example, a "prophylactic" epidural
      instituted soon after the beginning of labour may be lifesaving in a patient with
      obvious signs of difficult intubation. A clear definition of safe standards of
      equipment and practices either to prevent. Mendelson's syndrome or to cope with a
      failed intubation drill is of greatest importance. Finally, comprehensive
      communication between the anaesthetic and obstetrical teams is one of the most
      useful ways to facilitate safer approach of the management of obstetric
      emergencies studies. Caesarean section for foetal distress.

PMID- 9033829
TI  - [Abdominal gunshot wounds. Ballistic data and practical management].
AB  - The mortality from abdominal gunshot wounds remains high, either in civilian or
      military cases. The severity factors of these wounds include bullet calibre and
      energy transfer of the missile. This paper studies some of the ballistics
      features of abdominal gunshot wounds. Practical guidelines are inferred
      concerning diagnosis and treatment of these wounds.

PMID- 9033830
TI  - [Abdominal syndromes and analgesia].
AB  - Despite physiological advances and recent progress in pain relief, early
      analgesia for patients with acute abdominal pain is not a conventional endpoint.
      In clinical practice, priority is often given to diagnosis and management
      decisions. There are few controlled trials to settle the issue and opinions are
      still divided. recent studies suggest than early and effective analgesia in acute
      abdomen does not interfere with diagnosis, and even facilitates initial
      examination. Various modes of analgesia can be considered.

PMID- 9033831
TI  - [Neurological accidents after epidural anesthesia in obstetrics].
AB  - Several neurological complications have been described after epidural
      anaesthesia, including direct trauma to the spinal cord or nerve roots, epidural
      haematoma, meningitis, epidural abscess, spinal cord infarction. neurologic
      toxicity of injected agents. In obstetric practice, these complications are very
      uncommon. However, their real occurrence may be underrated, partly for
      medicolegal reasons. Different complication mechanisms are described; they should
      be kept in mind while evaluating post block neurological deficits so that prompt
      corrective measures can be taken whenever appropriate to prevent permanent
      damage.

PMID- 9033832
TI  - [Monitoring of multiple trauma in an emergency hospital unit].
AB  - In the monitoring of multiple trauma patients in the emergency hospital setting
      the use of monitors should be graduated. However, the use and interpretation of
      data from these monitors is becoming increasingly complex and can lead to errors
      and responses which may not be adopted. Clinical nomination and observation have
      their limits and the anaesthetist is faced with the added difficulties of
      interpretation of data from monitors and is pitfalls. The management of the
      patient is based on this human-machine relationship, which provides the basis for
      the therapeutic attitude and the treatment which ensues. Basic monitoring
      comprises a pulse oximeter, a capnograph, an ECG and a blood pressure monitor,
      52% of incidents are detected by these instruments; 27% by SpO2, 24% by
      capnography. The pertinence is 82% for the oximeter when used alone and 55% for
      the capnography alone, although when the two are used together this increases to
      88%. If the blood pressure monitor is added the pertinence increases to 93%, and
      to 95% if the FiO2 is monitored. The use of monitors of levels of haemoglobin or
      haematocrit must take into account the important variations in volaemia. The
      displayed values have a poor predictive value. The second level of monitoring
      comprises the use of a pulmonary artery catheter. The errors in measurement and
      interpretation are reviewed and finally, we consider the possible use of FOE
      transoesophageal echocardiography in the multiple trauma patient.

PMID- 9033833
TI  - [Respiratory arrest after retrobulbar anesthesia. Apropos of 2 cases].

PMID- 9033834
TI  - [Mesenteric infarction secondary to antithrombin III deficiency].
AB  - AT III is a physiologic inhibitor of blood clot formation: its deficiency is
      manifested by venous thrombosis. The authors reported case of mesenteric venous
      infarction in a 42-years-old woman. AT III deficiency was transient and caused by
      an oral contraceptive. In patients with AT III acquired deficiency it is
      necessary to suppress any risk factors of venous thrombosis.

PMID- 9033835
TI  - [Anesthetic problems of epidermolysis bullosa dystrophica. Apropos of a case].
AB  - Epidermolysis bullosa is a group of hereditary diseases of the skin that may also
      involve mucous membranes, particularly of the oropharynx and oesophagus. The
      common primary feature is the formation of blisters following even trivial
      trauma. During the management of anaesthesia, it is critical that trauma to the
      skin and mucous membranes be avoided or minimized in these patients. We report
      the case of a 3-year-old child who had two surgeries and discuss the anaesthetic
      implications of this disease.

PMID- 9033836
TI  - [Gas embolism during laparoscopic cholecystectomy].

PMID- 9033837
TI  - [Unilateral spontaneous adrenal hematoma during the postpartum period. Apropos of
      a case].
AB  - Spontaneous unilateral haematoma of the adrenal gland in post-partum is a rare
      event. We report a case in a 20 year-old woman without any medical history. The
      diagnosis could be suspected on upper abdominal pain and confirmed by sonography
      and CT-scan. There was no sign of endocrine dysfunction. Laboratory data were
      helpful to eliminate a phaeohromocytoma and histologic examination revealed only
      unilateral adrenal haemorrhage without tumour. Haematoma of the adrenal gland
      should be suspected in patients with upper abdominal pain without previous
      trauma, stress, or infection: however it occurs more frequently after severe
      stress and in association with other conditions. Surgery should be as
      conservative as possible.

PMID- 9033838
TI  - [Lithium poisoning].
AB  - A case of therapeutic overdosage in a 58-year-old woman is reported. Lithium
      plasma level was 3.7 mmol.l. All clinical and biological disturbances regressed
      in 3 days after controlled rehydration only. Aetiology, clinical picture,
      biological characteristics and treatment according to the severity of the lithium
      poisoning are discussed.

PMID- 9033839
TI  - [Algodystrophies: diagnosis].

PMID- 9033840
TI  - [Preoperative normovolemic hemodilution].

PMID- 9033841
TI  - [Epidural analgesia in the surgery of scoliosis].

PMID- 9033842
TI  - A lobster cysteine protease with immunoreactivity and activities of calcitonin
      and CGRP.
AB  - The high concentrations of molecules immunologically related to salmon calcitonin
      (CT) and/or to human calcitonin gene-related peptide (CGRP) in the oesophagus of
      the norway lobster Nephrops norvegicus have been examined. In the present study.
      We report the purification of these molecules by means of a specific
      radioimmunoassay for calcitonin and calcitonin gene related peptide. The
      immunoreactive molecules were tested for their functional similarities with CT
      and CGRP. This was investigated by measuring their ability to interact with CGRP
      and CT radioreceptor assays and to stimulate the adenylate cyclase activity in
      rat liver and kidney membranes, respectively. In addition, the purified product
      was injected in young rats in order to check for a CT-like biological activity of
      these molecules. The combination of these tests led us to purify a molecular form
      of 33 kDa. N-terminal sequence analysis of this protein revealed a considerable
      homology with the lobster cysteine proteases and the human cathepsin L. Control
      experiments performed with the highly purified American lobster cysteine protease
      I showed that crustacean cysteine proteases given in vivo to rats induce a fall
      in the plasma calcium and phosphate levels. This study therefore adds further
      documentation for a common ancestral origin of CT, CGRP and the much large
      cysteine proteases from invertebrates.

PMID- 9033843
TI  - [Cloning, expression and characterization of HIV-1 gp60 partially or completely
      deleted in the V3 loop].
AB  - In order to better understand the role of the immunodominant V3 loop in the type
      specific immune response and also to determine if this sequence has a role in
      AIDS pathogenesis, notably in the induction of apoptosis in CD4+ cells, we have
      introduced 2 modifications in the env gene from pNL4-3: a partial deletion in the
      V3 loop, keeping only the conserved tip of the loop GPGRAF consensus sequence
      (env delta V3-GPGRAF) and, secondly, a complete deletion of V3 sequence plus 43
      nucleotides in C3 (env delta V3+). These constructions as well as the non
      modified env gene, were cloned and expressed in a baculovirus system. Western
      blot analysis has shown that both modified env gene products reacted with a
      reference anti-HIV-1 serum to the same extent as the non-modified gp 160.
      However, in contrast to the non-modified env-protein and to env delta V3-GPGRAF,
      the env delta V3+ protein failed to bind to CD4 molecule, although V3 is not
      directly involved in receptor binding. These modified and non-modified
      recombinant proteins will be very useful to determine the potential of the
      partially or totally V3-deleted gp 160 to induce broadly reactive neutralizing
      antibodies and also to determine if V3 has a role in certain aspects of HIV
      induced pathogenesis, notably apoptosis.

PMID- 9033844
TI  - [The role of the transforming growth factor beta 1 (TGF-beta 1) and of vascular
      endothelial growth factor (VEGF) on the in vitro angiogenesis process].
AB  - We have studied the role of 2 exogenous cytokines, the TGF beta 1 and the VEGF,
      on the in vitro angiogenesis process. Endothelial cells were plated on fibrin
      matrices either with 2% or with 10% human serum in 199 medium. Forty-eight hours
      later, with 10% human serum, the capillary-like network index (the percentage of
      the culture area covered by the capillary network) was about 50%. Under these
      culture conditions, when TGF-beta 1 or VEGF were added, the capillary-like
      network index augmented and was nearing 75%. When the index is high, using
      confocal microscopy, we show that hollow capillaries are formed. Moreover, the
      addition of VEGF increased the kinetics of the capillary-like network formation.
      With 2% human serum, 48 h after seeding the capillary-like network index was
      about 75%. In this case, the addition of TGF-beta 1 decreased the network index,
      whereas the addition of VEGF increased the kinetics of its formation. These in
      vitro angiogenesis experiments show that the serological factors underline the 2
      antagonist effects of TGF-beta 1, but have no detectable effects on the activator
      effects on the VEGF.

PMID- 9033846
TI  - Partial purification of the pig kidney cystic fibrosis transmembrane regulator
      protein.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a transmembrane
      protein that is expressed in several epithelia, including kidney tubules.
      Mutations in CFTR (a PKA-chloride channel and/or regulator of other epithelial
      channels) give rise to the clinical manifestation of cystic fibrosis, and result
      in the synthesis of mutated proteins responsible for altering ion transport
      across secretory epithelia. The low abundance of endogenous CFTR makes a
      difficult to purify enough of the native protein to prepare anti-CFTR antibodies.
      We have used differential centrifugation to prepare cortical brush border
      membrane vesicles from pig kidney, cBBMV, and developed a method for the partial
      purification of CFTR. This is the first step in the isolation of native CFTR. The
      results show that CFTR is present in cBBMV. The purified protein will provide a
      clearer picture of the biophysical and biochemical properties of native CFTR.

PMID- 9033845
TI  - Human erythroid spectrin alpha subunit and its SH3 domain are sensitive to acidic
      Plasmodium falciparum proteolytic activity.
AB  - Many proteases play a crucial role in the Plasmodium intraerythrocytic life
      cycle. Spectrin depletion, one of the major events involved in parasite release
      from the red blood cell, results from proteolytic activities associated with the
      presence of the intracellular parasite. Here, we describe a new acidic
      proteolytic activity from Plasmodium falciparum, whose target is the alpha
      subunit of human spectrin. Immunoblotting experiments with antibodies specific
      for the tryptic peptides of the alpha-chain and in vitro proteolysis tests on
      recombinant peptides from different regions of the spectrin alpha subunit
      demonstrated that cleavage sites for the parasite proteolytic activity were
      localized within the SH3 motif of the alpha-chain sequence. Remarkably, this
      Plasmodium protease activity on spectrin SH3 substrate was unable to cleave the
      SH3 from fodrin, a non-erythroid spectrin.

PMID- 9033847
TI  - [Chronic hepatitis C: therapeutic uncertainties].

PMID- 9033848
TI  - [Chronic hepatitis C: therapeutic uncertainties. The virologist's point of view].

PMID- 9033849
TI  - [Economics and health policy: the example of hepatitis C viruses].

PMID- 9033850
TI  - [Prevalence of serum anti-hepatitis C virus antibodies and risk factors of
      contamination in the personnel of a hospital in the Paris region. A prospective
      survey].
AB  - OBJECTIVES: The aim of this prospective study was to estimate the prevalence of
      subjects with serum anti-HCV antibodies in a University Hospital in the Paris
      area, and to identify the risk factors associated with contamination. METHODS:
      Over an 18 month period, each person working in the hospital was systematically
      requested to fill out an anonymous questionnaire including 23 questions and to
      undergo a blood test for an anti-HCV assay during their annual medical visit.
      RESULTS: 557 (33%) of 1693 employees accepted to fill out the questionnaire and
      the anti-HCV assay. Serum anti-HCV antibodies were present in 9 subjects, which
      represents a prevalence of 1.6%, and serum RNA was positive by PCR, m 7. The
      prevalence was significantly higher in subjects working in clinical units (3.0%)
      compared to subjects working in non-clinical units (0.7%: P = 0.04) and in
      subjects with a history of acute hepatitis (5.5% vs 0.9%; P = 0.002%) Anti-HCV
      positive subjects had more history of manipulating blood products than HCV
      negative subjects (17.0 vs 8.8 years of exposure; P = 0.01), other human samples
      (17.0 vs 7.6 years; P = 0.01), and of having at risk contacts (16.7 vs 6.2 years;
      P = 0.0004). CONCLUSION: These results suggest the importance of systematic anti
      HCV screening among health care workers particularly those in contact with
      patients.

PMID- 9033851
TI  - [Hepatotropic virus and renal transplantation].

PMID- 9033852
TI  - [Why and how to carry out studies of quality of life in gastroenterology?].

PMID- 9033853
TI  - [Quality of life in chronic inflammatory bowel diseases. Validation of a
      questionnaire and first French data].
AB  - Inflammatory bowel diseases have an important impact on the daily life of
      patients. This impact can be measured by the evaluation of the health related
      quality of life. The aim of this study was to develop and to validate a
      questionnaire of quality of life in a French population. METHODS: The
      questionnaire comprised 70 items and was completed in 15 min. It was made up of
      a) a general questionnaire of 36 items (SF-36) exploring daily physical and
      social functioning, mental and general health, body pain and vitality. A sleep
      module of 6 items was added. b) a specific questionnaire of 28 items (RFIPC),
      exploring the concerns of the patients. The questionnaire was self-administered
      to 101 patients with Crohn's disease (57 F. 44 M. mean age: 35 years, acute
      disease: 28%, inpatients: 27%), 96 patients with ulcerative colitis (38 F. 58 M.
      mean age: 39 years, acute disease: 53%, inpatients: 21%). Each patient was sex
      and age matched with a healthy control. RESULTS: The psychometric analysis
      confirmed the validation of the questionnaire for the item's convergent validity,
      internal consistency (Cronbach's coefficient being > 0.70), analyses of
      discrimination. Scores of each scale of SF-36 were worse in patients than in
      controls. Scores of patients with active disease were worse than those of
      patients with quiescent disease. Scores were comparable in patients with Crohn's
      disease and with ulcerative colitis except for score of pain which was worse in
      acute Crohn's disease. The most important concerns of patients were the uncertain
      nature of the disease, energy level and having surgery. CONCLUSION: This study
      allowed the validation of a questionnaire for the evaluation of the quality of
      life in French patients with inflammatory bowel disease and provides first
      indications which need to be confirmed by future epidemiological studies.

PMID- 9033854
TI  - [Simultaneous study of tones of the lower esophageal sphincter and proximal
      stomach in healthy humans].
AB  - OBJECTIVES: The aim of this study was to determine the feasibility and tolerance
      of simultaneous assessment of the proximal gastric and lower esophageal sphincter
      tones in healthy humans, in fasting and fed conditions. METHODS: Esophageal
      motility and lower esophageal sphincter tone were measured on two separate days
      in 7 healthy subjects. During one of these sessions, proximal gastric tone was
      simultaneously assessed with a balloon placed in the proximal stomach and
      connected to an electronic barostat. Motility was monitored 1 hour before and 4
      hours after a liquid fat meal (400 mL/600 kcal). In four other healthy subjects,
      simultaneous assessment of proximal gastric and lower esophageal sphincter tones
      was performed after, suggestion of a 200 mL/200 kcal liquid meal. RESULTS:
      Simultaneous use of gastric barostat and esophageal motility device was well
      tolerated in 10/11 healthy subjects. The presence of the barostat balloon did not
      significantly affect basal lower esophageal sphincter tone and the rate of
      transient lower esophageal sphincter relaxations. The important fall of lower
      esophageal sphincter basal tone after ingestion of the 400 mL/600 kcal meal did
      not allow to detect a post-prandial increase of transient lower esophageal
      sphincter; relaxations. After ingestion of the 200 mL/200 kcal meal, the
      incidence of transient lower esophageal sphincter relaxations increased (p < 0.02
      vs. fasting). Maximal gastric relaxation was reached 15 min after meal, and
      appeared shorter (112 +/- 17 min vs. 167 +/- 24 min) and more pronounced (292 +/-
      26 mL vs. 190 +/- 51 mL) than after the 400 mL meal, but differences were not
      statistically significant. CONCLUSIONS: Simultaneous assessment of proximal
      gastric and lower esophageal sphincter tone is feasible, after oval ingestion of
      a meal. Since the 400 mL meal induces in important inhibition of lower esophageal
      sphincter basal tone, the 200 mL meal seems more adequate for assessment of the
      transient lower esophageal sphincter relaxations.

PMID- 9033855
TI  - [Role of nitric oxide in maintaining the mucosal integrity and in inflammatory
      gastrointestinal diseases].

PMID- 9033856
TI  - [Biological diagnosis of viral hepatitis. Recommendations and medical references.
      Agence Nationale pour le Developpement de l'Evaluation Medicale].

PMID- 9033857
TI  - [Pseudocystic metastases of carcinoma of the uterine cervix mimicking polycystic
      liver disease].
AB  - Pseudocystic liver metastases are rare and mainly described in neuroendocrine or
      ovarian tumors. We report the case of a 46-year-old woman who presented with
      multiple hepatic metastases mimicking polycystic liver disease. Carcinoma of the
      uterine cervix had been diagnosed 9 years earlier, and initially treated by
      radiumtherapy and surgery. Although histological post mortem examination of the
      pseudocystic liver metastases was not characteristic, they were related to the
      uterine cervix carcinoma for the following reasons: no other primary tumor was
      discovered, especially carcinoid or ovarian tumors: immunostains were positive
      for epithelial cells and negative for the neuroendocrine panel: the cystic
      cerebellum metastasis had a typical histologic aspect. Uterine cervical carcinoma
      must thus be included in the list of tumors which may form cystic hepatic
      metastases.

PMID- 9033858
TI  - [Hematemesis disclosing hemorrhagic fever with renal syndrome].
AB  - We report a case of hematemesis as the presenting sign of hemorrhagic fever with
      renal syndrome. Gastroscopy revealed hemorrhagic gastropathy. Such lesions are a
      common finding in epidemic nephropathy, the European form of the disease. The
      occurrence of such lesions could be induced in a direct, cytopathic effect of the
      virus but seems also to be related to the severity of thrombocytopenia.

PMID- 9033859
TI  - [A rare cause of obstructive jaundice: peripancreatic pseudoaneurysm].
AB  - We report the case of a 54-year-old-man with alcoholic calcified chronic
      pancreatitis complicated by jaundice and abdominal pain. Investigations (Doppler
      ultrasonography examination and computed tomography scan) showed peripancreatic
      pseudoaneurysm of the posterior and inferior pancreatico-duodenal artery and a
      dilatation of the common bile duct. Selective embolization of the pseudoaneurysm
      resulted in rapid regression of both jaundice and abdominal pain. Common bile
      diet compression is a rare complication of peripancreatic pseudoaneurysm.
      Selective embolization seems to be the first line treatment in this indication.

PMID- 9033860
TI  - [Treatment of refractory hydrothorax in liver cirrhosis by pleuro-peritoneal
      shunting].

PMID- 9033861
TI  - Hepatic localisation of an aggressive Kaposi's sarcoma leading to liver graft
      failure.

PMID- 9033862
TI  - [Painful acute liver involvement related to ingestion of fenofibrate].

PMID- 9033863
TI  - [Varicella and primary achalasia of the lower esophageal sphincter].

PMID- 9033864
TI  - [Diarrhea following the replacement of percutaneous endoscopic gastrostomy tube:
      to think of gastrocolic fistula].

PMID- 9033865
TI  - [Celiac disease and collagenous colitis: clinical and immunological study].

PMID- 9033866
TI  - [Multiple ruptures of the internal sphincter after anal rape: an underknown cause
      of fecal incontinence].

PMID- 9033868
TI  - [Management and transmission of medical images. Main standards and norms].
AB  - Use of digital images is growing in medical imaging. To be efficient, up-to-date
      concepts such as distributed informatics and client/server architecture must be
      used. Interoperability and networks adapted to the data involved in medical
      imaging are prerequisites to the implementation of such concepts. This
      necessitates official and de facto standards. Users of medical imaging should be
      aware of these standards and insist on the implementation of such standards on
      imaging equipment. This paper presents a survey of the main standards suitable
      for medical image management and transmission. Particular attention is focused on
      DICOM which is becoming the worldwide recognized standard in the field of medical
      imaging.

PMID- 9033867
TI  - [Magnetic resonance imaging of temporal lobe epilepsy].
AB  - MR has gained more and more importance in the evaluation of patients with
      temporal lobe epilepsy (TLE). Until recently, hippocampal sclerosis (which is the
      most frequent cause of temporal lobe epilepsy, accounting for 50-70% of the
      cases) could not be identified reliably. Using optimized magnetic resonance
      imaging techniques, hippocampal sclerosis can now be evidenced in a large
      proportion of patients with TLE. Tumors (10-15%), developmental abnormalities (5
      7%), vascular malformations (mostly cavernous angiomas, 1-5%), and traumatic
      scars (5-10%) represent the other structural lesions associated with TLE. Studies
      of large series of patients with intractable epilepsy or with varying severity
      have shown that in only 8.5% and 20%, respectively, a specific imaging
      abnormality was not found. Specific MR sequences increase the diagnostic value of
      MR (coronal images perpendicular to the axis of the hippocampal formations, three
      dimensional T1 weighted images, inversion recovery images, volumetry or more
      specific processes such as T1 and T2 relaxometry or spectroscopy). MR also helps
      guide placement of intra-cerebral and subdural electrodes in surgically relevant
      cases. All these results have given greater importance to MR in the definition of
      the epileptic syndrome of TLE and should probably be integrated in the criteria
      of international classifications.

PMID- 9033869
TI  - [Test of a teleradiology network based on ATM (asynchronous transfer mode)].
AB  - The retain project (Radiological Examination Transfer on ATM Integrated Network)
      consisted in teleradiology trials focused on pediatric imaging between two
      university hospitals. Rennes (France) and Barcelona (Spain) using an integrated
      broadband communication network based on ATM (asynchronous transfer mode), as
      part of a European research program. The network used was a full 10 Mbits/s ATM
      network directly connected to local PACSs (medical imaging hospital networks).
      One important reason to explicitly consider ATM for medical imaging is that
      multimedia applications on such networks allow integration of digital data and
      person-to-person communication. The utility of broadband communication for
      teleradiology has been confirmed. High quality video and sound are important for
      both human communication and medical video transfer. The project led to
      guidelines regarding technical options still open to improvement.

PMID- 9033870
TI  - [Photostimulation plates or conventional films for bedside chest x-ray in
      pediatric radiology? A comparative study of quality of image and the dose
      delivered to patients].
AB  - Image quality and patient doses received during chest bedside examinations
      performed with conventional (film-screen combination) and photostimulable
      phosphorus plate systems were compared in a study carried out in 1993 in a French
      pediatric radiology department. Seventy one children (36 males and 35 females)
      aged between 9 days and 18 years (average: 43 months) were included in the study.
      Technical performances of all radiological equipment used were permanently
      checked through a quality control program. One conventional and 3
      "photostimulable" films were performed for each patient included (mAs product
      selected for "photostimulable" system was progressively reduced down to 60% of
      that of conventional technique). TLD Lithium Fluoride chips were used to measure
      entrance surface dose during the examination. Image quality of 284 films (213
      "photostimulable" + 71 conventional) was assessed by three independent
      radiologists. Advantages and drawbacks of both studied imaging techniques are
      discussed in terms of patient dose reduction and image quality.

PMID- 9033871
TI  - [Value of plain abdominal radiography for evaluating the patency of LGM caval
      filters].
AB  - OBJECTIVES: To evaluate the value of plain abdominal X-Ray to detect vena Tech
      LGM filter occlusion or patency during follow-up. METHODS: Eighty-nine patients
      were followed in a prospective study for 2 to 6 years after vena Tech LGM filter
      implantation. The control examination consisted in a clinical examination, a
      plain abdominal X-Ray (to measure expansion index = diameter/height of the filter
      and to detect migration and angulation) and a Doppler ultrasonography and/or a
      cavography to appreciate filter patency. RESULTS: 175 plain abdominal X-Ray, 172
      Doppler ultrasonographies and 28 cavographies were done. Sensitivity and
      specificity of retraction to suspect a filter obstruction were respectively:
      82.3% and 86.1%; if expansion index was lower or equal to 0.34 its sensitivity
      and specificity were 100% and 92.1%. The negative predictive values of retraction
      and of the association retraction-migration to exclude a filter obstruction were
      85.1% and 96%. CONCLUSION: Absence of migration or retraction on plain abdominal
      X-Ray during the follow-up is highly predictive of filter patency. This limits
      the use of Doppler ultrasonography and cavography.

PMID- 9033872
TI  - [Erratic course of bilateral renal angiomyolipomas].
AB  - We report a case of multiple and bilateral renal angiomyolipomas demonstrated and
      followed up by urography, sonography, and computed tomography during a period of
      17 years. The diagnosis has been made by computed tomography. Follow-up
      examinations showed first a stability of the lesions, and afterwards, a rather
      fast increase of the volume of various masses, without symptoms, followed by a
      new period of stabilization.

PMID- 9033873
TI  - [Imaging of symptomatic giant hemangioma].
AB  - A case of symptomatic giant hemangioma of the liver with fever, anemia, and
      increased erythrocyte sedimentation rate is reported. Spontaneous hyperdense
      areas at CT, and high signal-intensity areas at T1-weighted MR images were
      demonstrated within the hemangioma. Marked hemorrhagic zones demonstrated at
      pathologic examination may explain these uncommon clinical and imaging features.

PMID- 9033874
TI  - [Easy creation of a kit of radiologic images with Microsoft Visual Basic].
AB  - As computer media have a well accepted role in the medical world, we suggest to
      residents and assistants specialized in imaging, an easy, evolutive and low-cost
      computer-based method, that allows to build up a picture data bank for use as a
      teaching tool. We join to this article, the output of our interface program.

PMID- 9033875
TI  - [To avoid cerebral ileus in abdominal ileus].

PMID- 9033876
TI  - [Percutaneous biliary prostheses. Type of material and indications].
AB  - The results of percutaneous transhepatic endoprosthesis in the treatment of
      biliary stenosis are discussed on the basis of the reports of the literature and
      a personal experience of more than 400 patients treated for about 15 years.
      Advantages and disadvantages of conventional stents as compared with metal
      endoprosthesis are discussed, the latter being now preferred by most authors.
      However they do not prove to be more efficient than conventional stents which are
      suitable for those patients who have a relatively short life expectancy.
      Percutaneous treatment of benign biliary stenosis has grown as well but the
      choice of the best procedure remains difficult. Metal endoprostheses are
      controversial because the risk of delayed obstruction has not yet been clearly
      evaluated. However it might become an interesting therapeutic procedure in the
      future.

PMID- 9033877
TI  - [Value of asymmetry criterion in MRI for the diagnosis of small pelvic
      lymphadenopathies (inferior or equal to 1 cm)].
AB  - The purpose of this study was to determine if lymph node asymmetry in small (<
      1.0 cm) pelvic nodes was a significant prognostic feature in determining
      metastatic disease. 216 patients who presented pelvic carcinoma underwent MR
      imaging. They were correlated to pathological findings obtained by surgery. We
      considered on the axial plan the maximum diameter (MAD) of both round or oval
      shaped suspicious masses. Two different cut-off values were determined: node
      diameter superior to 1.0 cm (criterion 1) and node diameter superior to 0.5 cm
      with asymmetry relative to the opposite side for nodes ranging from 0.5 cm to 1.0
      cm (criterion 2). With criterion 1 MR Imaging had an accuracy of 88%, a
      sensitivity of 65%, a specificity of 96%, a PPV of 88% and a NPV of 88% in
      detection of pelvic node metastasis. By considering criterion 2, MR Imaging had
      an accuracy of 85%, a sensitivity of 75%, a specificity of 89%, a PPV of 71% and
      a NPV of 91%. Normal small asymmetric lymph nodes were present in 5.6% of cases.
      Asymmetry of normal or inflammatory pelvic nodes is not uncommon. It cannot be
      relied on to diagnose metastatic involvement in cases of small suspicious lymph
      nodes, especially because of its low specificity and positive predictive value.

PMID- 9033878
TI  - [Sedation with oral hydroxyzine and rectal chloral hydrate in pediatric MRI and
      CT].
AB  - AIM: To assess the efficacy and risks of oral hydroxyzine and rectal chloral
      hydrate to sedate children undergoing CT or MRI. PATIENTS AND METHODS: 110
      children underwent 117 studies. Medical history, treatments, doses per kg of
      sedative drugs, study quality, sedation time and side effects were prospectively
      recorded. RESULTS: 25 minutes was the mean time necessary to put children to
      sleep, 59 minutes was the mean time of sedation 96% of studies were
      interpretable. 2 children showed transient side effects. CONCLUSION: This
      sedation regimen appeared efficient. However, its limitations and risks have to
      be known by radiologists. Sedation-related problems also have to be considered by
      hospital managers when a new CT or MR equipment is being acquired.

PMID- 9033879
TI  - [Cervico-mediastinal recurrences of differentiated thyroid cancers: value of
      MRI].
AB  - AIM: The aim of this study was to evaluate the ability of MRI to detect recurrent
      differentiated thyroid carcinomas developed in the neck or the upper mediastinum.
      RESULTS: MRI was performed in 25 patients, and was compared in 5 cases with
      surgery. In 20 cases it was compared with I-131 scintigraphy (100 mCi in 14 cases
      and 5 mCi in 6 cases). The sensibility, specificity and overall accuracy of MRI
      was respectively: 100%, 66.6%, 82.6%. COMMENTARY: MRI is a good technique to
      detect recurrent thyroid carcinomas. It is specially interesting to investigate
      patients with a biological suspicion of recurrence and a negative scintigraphy.
      Mediastinal localisations that cannot be detected by US can be detected by MRI.

PMID- 9033880
TI  - [Tumor vascularization: contribution of Doppler ultrasonography].
AB  - PURPOSE: The purpose of this study was to evaluate the usefulness of Doppler
      sonography in quantifying tumor vascularization and in determining hemodynamic
      parameters by spectral analysis. MATERIALS AND METHODS: A total of 100 malignant
      tumors of different histologic types, were prospectively studied with spectral,
      color-coded and power Doppler sonography (Toshiba 140 A with 3.75 and 7.5 MHz
      probes). Internal or peripheral vascularization was scored from 0 (absence of
      color flow) to +3 (numerous vessels inside and/or beside the mass). Three
      parameters were calculated for each arterial waveform recorded: the peak systolic
      velocity (PSV, n = 84), the resistive index (RI, n = 130) and the pulsatility
      index (PI, n = 115). RESULTS: Tumoral vascularization was scored 0 in 13 cases, +
      in 39 cases, +2 in 29 cases and +3 in 19 cases. The mean value of the PSV was
      about 0.30 m/s. RI values ranged from 0.35 to 1 (mean = 0.63). PI values were < 1
      in 28 cases and > 2 in 15 cases (mean = 1.68). CONCLUSION: Our results confirm
      the wide variability in tumor vascularization and in hemodynamic parameters
      values in malignant tumors.

PMID- 9033881
TI  - [Imaging of Erdheim-Chester disease].
AB  - Erdheim-Chester disease is a form of Histiocytosis which involves the adults and
      is distinct from Histiocytosis X. It is characterized by a constant diaphyseal
      and metaphyseal bone involvement predominating in the lower links. The diagnosis
      can readily be envisaged when the typical radiological findings are present. Bone
      involvement may be isolated and well tolerated, or can be associated with
      systemic involvement and a severe prognosis. We describe three cases of women
      aged 46, 50 and 73 years. One patient presented with isolated bone lesions, while
      the two others had a multiorgan localization. From the three cases and from an
      extensive review of the literature, we describe the spectrum of bone and visceral
      lesions that can be seen by imaging. The emphasis is put on lesions of the
      skeletal system, the retroperitoneum, the nervous system, and the pericardium.
      Furthermore, the relationships between Erdheim-Chester disease and Histiocytosis
      X are discussed.

PMID- 9033882
TI  - [Value of echography in the diagnosis of acute intestinal occlusion].
AB  - OBJECTIVE: The aim of our study was to assess the value of sonography in the
      diagnosis of acute intestinal occlusion. MATERIAL AND METHODS: Sonographic
      findings were reviewed in 50 cases of intestinal occlusion (39 small bowel and 11
      colonic occlusions). The final diagnosis was based on surgical findings (n = 40)
      or clinical course and further imaging findings (n = 10). RESULTS: Occlusion was
      correctly detected with sonography in 48 cases (96%). The location was correctly
      established with sonography in 43 cases (86%). The precise cause was suggested
      with sonography in 21 cases (42%). COMMENTARY: These results confirm the value of
      sonography for the diagnosis of intestinal occlusion and the identification of
      its level and its cause.

PMID- 9033883
TI  - [Hepatic hamartoma in adults. Apropos of a case documented by MRI].
AB  - A mixed hamartoma of the liver in a 39 year old man is reported. Abdominal
      ultrasound revealed a 4 cm inhomogeneous echogenic mass with acoustic shadowing.
      MRI T1 weighted images showed a inhomogeneous low intensity mass with lower
      gadolinium enhancement than normal liver, a moderate low signal intensity on
      proton density weighted images, and heterogeneous isosignal intensity on T2
      weighted images. Peripheric calcifications were found on pathologic examination.

PMID- 9033884
TI  - [Focal nodular hyperplasia and spontaneous intrahepatic porto-portal
      communication].
AB  - One case of typical focal nodular hyperplasia of the liver on CT but not proven
      at pathology was associated with a variation of the intrahepatic portal venous
      system. The absence of the horizontal segment of the left portal vein with portal
      supply between the anterior segmental branch of the right portal vein and the
      umbilical portion of the left portal vein was observed. This finding observed is
      significant for planning liver surgical procedure such hepatic lobectomy as the
      incision would interrupt the portal supply.

PMID- 9033885
TI  - [Subarachnoid rupture of supratentorial dermoid cyst: CT and MRI aspects].
AB  - We report a case of ruptured subarachnoid dermoid cyst which was explored with
      both CT and MRI. This rare condition results from the accumulation of a large
      amount of fat with a characteristic aspect at-imaging. Rupture causes fat
      dissemination in the subarachnoid space. In most cases, CT or MRI can provide
      sure diagnosis of the tumor and of rupture.

PMID- 9033886
TI  - [Tuberculous femoral osteitis].

PMID- 9033887
TI  - [Non-penetrating deep sclerectomy combined with a collagen implant in primary
      open-angle glaucoma. Medium-term retrospective results].
AB  - PURPOSE: To evaluate the middle term tonometric results of a new filtering
      procedure, the non penetrating deep sclerectomy with collagen device, in primary
      open-angle glaucoma. This technique aims to eliminate or minimize the
      complications of classical trabeculectomy. MATERIAL AND METHOD: This procedure
      has been developed by Koslov et al. Under a limbal-base conjunctival flap and a
      superficial scleral flap, the ablation of a deep scleral flap takes away the
      external wall of Schlemm's canal, leaving only the Descemet membrane. A visible
      filtration across the opened Schlemm's canal and Descemet membrane is obtained.
      To improve the aqueous filtration, a cylindric collagen device, made from
      biocompatible porcine scleral tissue, known for its high water content, is fixed
      in the deep scleral bed with a 10/0 nylon suture. This device provides a support
      for the elimination route of aqueous humor and acts like a sponge, carrying the
      liquid by capillary action. It is sterilized by irradiation. Full guarantee
      against viral contamination is provided. This procedure ends in one suture (40/0
      nylon) of superficial scleral flap and conjunctival closing suture. We conducted
      a retrospective study. Our material included 159 patients (92 males, 65 females),
      2/9 eyes. The mean age was 65 years (11-91). The mean follow-up : 8 months (3
      20). The types of glaucoma were: POAG: 183 eyes; juvenile POAG: 18 eyes:
      pigmentary glaucoma: 11 eyes; capsular glaucoma: 7 eyes, 58 eyes (40 patients)
      presented one or several risk factors of failure for filtering surgery. RESULTS:
      The mean pre-operative IOP was 24 mmHg +/- 6.60; 15.7 +/- 5.30 at the end of the
      follow-up (delta average IOP: 9.1 +/- 7.1). The probability success rate (IOP <
      or = 20 mmHg), according to the Kaplan-Meier Method, was 89% at six months, 75.6%
      at 16 months. With monotherapy with beta blockers, 79% at 16 months. It was
      better in the without risk factors group. The mean change in visual acuity was
      inferior to 0.1 at the end of the follow-up. Except several hyphemas, no
      complications of the trabeculectomy were observed. The reelevation of IOP was due
      to an internal obstruction (goniosynechiae or bad filtration), it was treated
      with Nd-Yag laser with a 2/3 of success rate. External obstruction was treated by
      5FU injections into the bleb. CONCLUSION: Non penetrating deep sclerectomy with
      collagen device can be an excellent alternative to trabeculectomy in open and
      wide angles. It does not modify visual actuity. It carries less complications
      than trabeculectomy and the use of antimitotic agents is safer.

PMID- 9033889
TI  - [Color vision test for detection and evaluation of dyschromatopsia].
AB  - METHODS: The color vision test for diagnosis and evaluation of the
      dyschromatopsias consists of a set of 92 colored test charts of the
      pseudochromatic type, a lamp and a test report giving a graphic image of the
      sensitivity to color deficiency. RESULTS: The test makes it possible to identify
      each neutral zone of all types of dyschromatopsia, places the neutral zone within
      the color spectrum and establishes its extent according to 6 axes (Protan,
      Deutan, Tritan, Tetartan, Scotopic and Monochromatic) and 10 levels. The visual
      sensitivity to color is measured on a 10 point scale, just as visual acuity is.
      Between a normal sensitivity to color, which is marked 1, and an anopia (i.e
      complete lack of visual sensitivity to color along one axis), marked 0, there are
      9 intermediary levels marked 0.9; 0.8: 0.7; 0.6: 0.5; 0.4; 0.3; 0.2 and 0.1.
      CONCLUSION: Testing is important for all kinds of eye diseases or common diseases
      which affect eyesight making possible not only early diagnosis of a disease but
      also treatment follow-up.

PMID- 9033888
TI  - [Control of photocoagulation intensity by thermo-induced release of a fluorescent
      marker encapsulated in liposomes: study of an in vivo vascular model].
AB  - PURPOSE: To evaluate the feasibility of thermal damage assessment of blood
      vessels by using laser-induced release of liposome-encapsulated dye. METHODS: A
      skin flap window model of aluminium was implanted on the loose skin on the back
      of adults Golden hamsters to expose skin blood vessels in vivo. Thermosensitive
      liposomes (DSPC) loaded with 5,6-Carboxyfluorescein were injected together with a
      specific Indocyanine green (ICG) formulation (O/W emulsion) in order to enhance
      diode laser absorption. Photocoagulations were then performed on the vessels with
      a diode laser (lambda = 810 nm, P = 0.8W, phi = 1.3 mm, 1 to 6s). Fluorescence
      measurements were realized with an ultra high sensitivity intensified camera
      (Hamamatsu Argus 50 imaging system). RESULTS: Two different fluorescence
      intensity curves corresponding to the variability of absorption of the targets
      were observed. Variability was related to the amount of ICG. For each curve, 3
      zones were identified: (i) for fluences ranging from 60 +/- 20 J/cm2 to 110 +/-
      20 J/cm2 a transient intravascular fluorescence was observed only for the loser
      pulses targeted on the vessels, (ii) for fluences ranging from 110 +/- 20 J/cm2
      to 190 +/- 20 J/cm2 a permanent fluorescent spot limited to the vessel was
      observed for the laser pulses targeted on the vessels; for the laser pulses
      targeted on the skin a transient low fluorescence circular spot was observed. For
      this fluence range a selective photocoagulation of a vessel was performed. (iii)
      for fluences ranging from 190 +/- 20 J/cm2 to 300 +/- 20 J/cm2 persistent intense
      fluorescence spots were observed on both skin and vessels. This type of
      fluorescence was related to an overdosage. CONCLUSION: These results are in fair
      agreement with the data of the literature about liposomes and with the data we
      obtained in a previous study on a vascular model. This study demonstrates the
      interest of a laser-induced release of liposome-encapsulated dye for a real-time
      quantification of thermal damage. Such a method could be useful for laser
      photocoagulation in ophthalmology for indications such as choroidal neovessels
      where the production of a precise thermal damage is required.

PMID- 9033890
TI  - [Efficacy and tolerability of a combination of indomethacin and gentamicin for
      preventing inflammation after cataract surgery].
AB  - PURPOSE: The aim of the study was to compare 2 combinations of anti-inflammatory
      drug and antibiotic, in patients undergoing cataract surgery: 0.1%
      indomethacin/gentamicin or 0.1% dexamethasone/ neomycin. METHODS: Two hundred and
      two patients undergoing extra-capsular cataract extraction with posterior chamber
      lens implantation were included in a randomized, double-blinded multicentric
      study comparing 2 parallel groups of treatment. Treatment was administered the
      day before surgery, the day of surgery and for the following 7 days. On the 8th
      post-operative day, the antibiotic was stopped and the anti-inflammatory
      treatment continued alone until the 30th post-operative day. Post-operative
      ocular inflammation was assessed clinically on the 1st, 7th, 15th and 30th post
      operative days. The main evaluation criterion of treatment efficacy was the
      assessment of anterior chamber flare and cells. RESULTS: No statistically
      significant difference-was observed between the 2 treatment groups concerning
      post-operative inflammation. Both treatments were well tolerated. CONCLUSION: Eye
      drops combining 0.1% indomethacin and gentamicin proved to be effective and well
      tolerated in preventing inflammation after cataract surgery.

PMID- 9033891
TI  - [Has the incidence of postoperative PVR in rhegmatogenous retinal detachment
      decreased?].
AB  - PURPOSE: To determine whether the incidence of severe postoperative PVR in
      primary rhegmatogenous retinal detachment has decreased over the last twelve
      years. MATERIALS AND METHODS: We prospectively evaluated 595 eyes of 554
      consecutive patients with primary rhegmatogenous retinal detachment, referred
      before any failed attempt to reattach the retina, managed by the same surgeon
      between March 1983 and December 1994. The eyes were divided into two consecutive
      series: 275 eyes operated on from March 1983 through February 1988 (series no.
      1), and 320 eyes operated on from February 1988 through December 1994 (series no.
      2). We conducted univariate and multivariate statistical analyses to compare the
      incidence of postoperative PVR in the two consecutive series. RESULTS: The
      overall incidence of postoperative PVR was 8.72% (24/275 eyes) in series no. 1,
      versus 2.81% (9/320 eyes) in series no. 2 (p < 0.01). The incidence of
      postoperative PVR in retinal detachments due to atrophic holes in lattice
      degeneration, oral dialyses, and macular holes in myopic eyes, was nil in both
      series. The incidence of postoperative PVR in retinal detachments due to
      horseshoe tears with mobile posterior edges was 1.16% (1/86 eyes) in series no.
      1, and 0% (0/109 eyes) in series no. 2. The incidence of postoperative PVR in
      retinal detachments associated with horseshoe tears with curled posterior edges
      was 21.15% (11/52 eyes) in series no. 1 versus 3.2% (3/93 eyes) in series no. 2
      (p < 0.001). The incidence of postoperative PVR in giant tears was 35.5% (11/31
      eyes) in series no. 1. and 14.7% (5/34 eyes) in series no. 2 (chi square = 3.77;
      at the limit of significance). The incidence of postoperative PVR in retinal
      detachments du to paravascular tears of the post-equatorial region in myopic eyes
      was 25% (1/4 eyes) in series no. 1, and 14% (1/7 eyes) in series no. 2.
      CONCLUSION: In our own experience, the incidence of postoperative PVR in primary
      rhegmatogenous retinal detachment has decreased at a statistically significant
      level since 1988. We believe that the decreased incidence of postoperative PVR in
      our most recent series is mainly related to the use of laser photocoagulation
      retinopexy rather than cryopexy in the management of high risk eyes (retinal
      detachments associated with horseshoe tears with curled posterior edges, and
      giant tears).

PMID- 9033892
TI  - [Strabismus in Cameroon].
AB  - PURPOSE: We undertook a study on strabismus in order to determine the
      characteristics of this disease in Cameroon. MATERIAL AND METHODS: A prospective
      study was carried out in the ophthalmological unit of the Douala General Hospital
      from November 1991 to October 1995. All patients were examined and followed
      regularly by the same team. RESULTS: We found 137 strabismus, which represent
      1.22% of all patients with 51 esotropias (37.2%) and 86 exotropias (62.8%). The
      mean age was 13.61 years at the first consultation. 82.4% of convergent
      strabismus appeared before the age of one year against 67.4% of divergent
      strabismus. Moreover, amblyopia was found in 68.6% and 59.3% of cases
      respectively. CONCLUSION: As compared to European series, this study shows
      notably the great frequency of divergent squint in black africans and the fact
      that spontaneous evolution of the latter can lead to amblyopia in a large number
      of cases.

PMID- 9033893
TI  - [Clinical aspect of the artificial trabeculum. A 6-month study in rabbits].

PMID- 9033894
TI  - [Multifocal choroiditis associated with herpes zoster ophthalmicus. Apropos of a
      case].
AB  - We describe a patient with multifocal choroidal lesions affecting the
      midperipheral fundus, with an atrophic and scattered punched-out pale aspect.
      Lesions were discovered seven months after an ipsilateral herpes zoster
      ophthalmicus. Fluorescein angiography findings exhibited a delay of choroidal
      injection and late moderate staining during the venous phase. The etiological
      arguments refer to a previous herpes zoster infection. The pathogeny would
      involve an occlusion of posterior ciliary arteries, lesions of posterior ciliary
      nerves and/or direct cytopathogenic involvement of chorioretina by neurotropic
      virus from ciliary ganglion.

PMID- 9033895
TI  - [Liposomes in opthalmology. Review of the literature].

PMID- 9033896
TI  - [Cataract and corneal endothelium].

PMID- 9033897
TI  - [Determination of physicochemical characteristics and evaluation of
      decontaminating efficacy and in vitro safety of cleaning products for contact
      lenses].
AB  - PURPOSE: This work aims to characterize products designed for cleaning contact
      lenses and particularly their physicochemical properties, their efficiency and
      their ocular irritancy potential compared to the main requirements of eye-washes.
      MATERIAL AND METHODS: The physicochemical controls include pH determination,
      viscosity and freezing point depression. In addition, we carried out the hydrogen
      peroxide assay for products containing this active substance. A microbiological
      control was performed when opening the product and after simulation of a 21-day
      aging. We determined the decontaminating efficacy of the products on four
      bacterial strains and a fungal strain. Finally, we tested their ocular allowance
      by an in vitro test. RESULTS: The pH values obtained ranged from 3.2 (oxygenated
      water solutions) to 7.6. The viscosity was close to a water solution one (about 1
      centipoise). The different assays showed hydrogen peroxide content similar to
      that stated on the package: rate averaged to 3% and was negligible after
      neutralization. At opening and after simulation the bacteriological quality was
      excellent. Finally, decontaminating efficiency against germs was very good for
      the products tested. The products were classified as non-irritant by the ocular
      irritancy test. CONCLUSION: The results obtained show that the products tested
      met the reference criteria, particularly eye-wash criteria.

PMID- 9033898
TI  - [Epinephrine stability in solutions for intra-ocular irrigations].
AB  - PURPOSE: Epinephrine may be used for ocular irrigation during ophthalmic surgery
      when diluted in balanced saline solutions. In aqueous solution, epinephrine
      breakdown depends on pH, light, temperature, oxidating agents and increases with
      time. METHODS: The stability of epinephrine in plastic bags prepared in low
      concentrations (1 mg/L) was studied by HPLC analysis with UV detection, completed
      with pH determinations, performed after storage (protected from light) in various
      conditions: at room temperature (+25 degrees C), at +4 degrees C (in a
      refrigerator), at -20 degrees C (in a freezer). Spontaneous defreezing at room
      temperature was compared to accelerated thawing in a microwave oven. RESULTS:
      Epinephrine diluted in ocular irrigation solutions (1 mg/L) was stable for 2 days
      at room temperature, 14 days at +4 degrees C and 35 days at -20 degrees C.
      Microwave thawing did not alter the stability of epinephrine. CONCLUSION: The
      preparation of epinephrine solutions for intra-ocular irrigation may be
      centralized if the bags are stored less than two weeks in a refrigerator and less
      than one month in a freezer.

PMID- 9033899
TI  - [Effects of external orbital radiotherapy on the oculomotor muscle in Graves
      disease].
AB  - PURPOSE: Orbital radiotherapy is recognised to be effective in the treatment of
      acute Graves' disease. The effect on the oculomotor muscles is still
      controversial. MATERIAL AND METHODS: To assess this effect, we conducted a
      prospective study on 15 patients with acute Graves' ophthalmopathy. Patients were
      investigated before radiotherapy, 3 months later and at long term (mean = 2
      years). To study the extent of the ophthalmopathy we chose the following
      criteria: class IV in the NOSPECS classification system, amplitude of gaze,
      measurement of the thickness of oculomotor muscles (CT-scan). RESULTS:
      Improvement of the amplitude of gaze and reduction of the thickness of oculomotor
      muscles were not statistically significant. The oculomotor disorder was unchanged
      3 months after radiotherapy. After a long term follow up (mean: 2 years), only 5
      patients, among those who complained of diplopia before radiotherapy, had to be
      operated, especially large deviations. CONCLUSION: Orbital radiotherapy does not
      appear as a direct treatment for oculomotor disorder in active thyroid related
      ophthalmopathy, however favorable indirect effects may be effective due to
      reduction of inflammation. As it is a harmless treatment, orbital radiotherapy
      may be proposed as primary treatment in active thyroid related ophthalmopathy.

PMID- 9033900
TI  - [Iodine 125 curietherapy of choroidal melanomas. Values of the technique and
      initial results].
AB  - PURPOSE: Among conservative treatment of the choroidal melanoma, improved
      functional capacities can be provided with Iodine 125 and with a treatment
      planning system for optimized dosimetry. METHODS: Forty patients were treated
      with Iodine 125 with a minimal follow-up period of 6 months and a mean follow up
      of 25 months. RESULTS: Response to the treatment based on tumor regression or
      stabilization was 97%. Complication rate was 32%. Retinopathy was the major cause
      of loss of vision and was linked to the proximity of the tumor to the macula. Two
      patients developed metastasis and one required enucleation for tumor regrowth.
      CONCLUSION: Brachytherapy with Iodine 125 was found to be effective on tumor
      growth within the limits of the follow-up. High doses (100 Gy) given to the apex
      of the tumor did not increase complications rate. Many years will be necessary to
      assess efficiency of such a procedure in terms of preventing complications.

PMID- 9033901
TI  - [Dural fistulae of the cavernous sinus and interventional neuroradiology. Apropos
      of 4 cases].
AB  - PURPOSE: Our purpose was to show how difficult it is to diagnose a dural fistula
      of the cavernous sinus, which is an anomalous arteriovenous shunt within the dura
      mater extending from meningeal arteries to the cavernous sinus. CASE REPORT: A
      dural fistula was suspected in four female patients aged between 61 and 80,
      presenting with a red eye, dilated episcleral veins, exophthalmos and elevated
      intraocular pressure. A cerebral hyperselective angiography was performed in all
      cases. RESULTS: The cerebral angiography confirmed the diagnosis of a dural
      fistula in all cases, showing the early filling of the cavernous sinus followed
      by the draining vessel (posterior in case n. 4, anterior in cases n degrees 1, 2,
      3). Case n degrees 2 was unilateral and cases n. 1, 3, 3 were bilateral. The
      blood flow was low in all cases. A successful embolization was performed in all
      patients with resolution of all symptoms. CONCLUSION: The diagnosis of dural
      fistulas is often difficult because of misleading clinical signs. It is
      documented by a cerebral angiography showing the feeding vessels and helping to
      choose either venous or arterial embolization which is the most suitable
      treatment.

PMID- 9033902
TI  - [Chloroquine maculopathy and prevention of malaria].
AB  - PURPOSE: Chloroquine maculopathy is a major complication observed during
      prophylactic treatment of malaria. We present here 18 cases recently documented
      at Lome Teaching Hospital. METHOD: Retrospective data of patients presenting with
      macular fluoroscopic bull's eye are analysed, all had a history of prophylactic
      treatment for malaria. RESULTS: These patients presented with three models of
      prophylaxy, total toxic doses were 185 g, 557 g and 1,300 g in the case of low,
      mild or high and massive continuous prophylaxy. All eighteen patients presented
      with macular angiofluorographic bull's eye; 11 were male, 7 female, mean age was
      41.72 years. CONCLUSION: Chloroquine retinopathy is a rare complication observed
      at our hospital. Because of the poor prognosis of the disease and our
      geographical situation in an endemic area, the threshold dose might be 185 g.
      Patients should have undergone systematic screening before these cumulative
      doses. The incidence of this major complication which could increase would
      question chloroquine prophylaxy with actual doses and methods.

PMID- 9033903
TI  - [Value of PMMA intracapsular rings during cataract surgery].
AB  - During cataract surgery, the stability of the capsular bag represents an
      important factor in the procedure and in the postoperative outcome. When this
      stability is poor in case of dialysis or phacodonesis, the use of an
      intracapsular PMMA ring may help in preventing possible complications.

PMID- 9033904
TI  - [Lipogranuloma of the orbit. Apropos of a case].
AB  - We present a case of orbital lipogranuloma with a supero-nasal retrobulbar
      localisation associated with axial proptosis and major choroidal thickening. No
      clinical sign of inflammation, neither orbital nor in the posterior segment, was
      revealed. The systemic work-up as well as paraclinical data were within normal
      limits. The diagnosis was made after histopathologic examination of the biopsy
      taken via superior orbit. Outcome was favorable following long-term systemic
      corticotherapy. Orbital lipogranuloma is a rare particular form of orbital
      pseudotumour of unknown etiology. It is characterized, histologically, by orbital
      fat necrosis. Pathogenesis remains controversial. The differential diagnosis
      includes iatrogenic lipogranulomas secondary to sinus surgery (paraffinoma),
      orbital granulomas in sarcoidosis and Wegener's disease and orbital lymphomas.
      The prognosis is usually good following treatment with steroids.

PMID- 9033905
TI  - [Central retinal artery occlusion related to ingestion of tranexamic acid].
AB  - A case of central retinal artery obstruction occurred in a 75-year-old patient
      after five days of tranexamic acid therapy. The mechanism of this obstruction was
      discussed in light of data found in the literature.

PMID- 9033906
TI  - [Surgery of macular holes].

PMID- 9033907
TI  - [Herpetic keratitis and corneal grafting].

PMID- 9033908
TI  - Susceptibility of rodents to infection with Schistosoma mansoni in Richard-Toll
      (Senegal).
AB  - The susceptibility of Arvicanthis niloticus, Mastomys huberti, Mastomys
      erythroleucus and Mus musculus was studied to assess the capacity of these
      rodents to transmit Schistosoma mansoni. The susceptibility was determined by the
      percentage of adult schistosomes recovered, the number of eggs per gramme of
      faeces, the viability of these eggs and the capacity of the rodents to maintain
      the life cycle of Schistosoma mansoni. The percentages of adult worms recovered
      were respectively 18%, 11.5%, 8.4% and 20.5% in A. niloticus, M. huberti, M.
      erythroleucus and M. musculus. After infection, they liberate in the environment
      viable eggs whose miracidia are infectious for the intermediate host
      (Biomphalaria pfeifferi). The mean egg load was 300 +/- 327.8 in A. niloticus;
      664 +/- 673.5 in M. huberti; 240 +/- 304.8 in M. erythroleucus; 400 +/- 361.5 in
      M. musculus.

PMID- 9033910
TI  - Stephanofilaria boomkeri n. sp., as a cause of severe skin disease in pigs in
      Zaire.
AB  - A new Stephanofilaria, S. boomkeri n. sp., is described as the cause of skin
      lesions in pigs in Zaire. It is the first species described in suids. The
      reservoirs might be wild African suids. The six valid species of the genus
      Stephanofilaria form two main groups. In one group, female worms lay sheathed
      microfilariae; members of this group are exclusively African and are represented
      by the parasite of rhinoceros, S. dinnicki, and hippopotamus, S. thelazioides.
      Their morphology is primitive. In the other group, female worms lay particular
      "eggs" which contain microfilariae S. boomkeri belongs to this group, and is
      regarded by its cephalic structures as the most primitive representative in this
      group. The other species S. dedoesi and S. zaheeri, parasitize cattle in the
      Asiatic region. In the holarctic region, another parasite of cattle, S., stilesi,
      seems to be a highly specialized member of this second group. In this species as
      in S. boomkeri, the envelope of the "egg" is very thick and complex, probably
      from peculiar adaptations in order to withstand the dessication of the
      microfilaria. The genus Stephanofilaria seems to have an Aethiopian origin, as in
      this region the species are more primitive and more varied as are also their
      hosts.

PMID- 9033909
TI  - [Changes in plasma lipid levels as a function of Plasmodium falciparum infection
      in Sao Tome].
AB  - Changes in lipid plasma levels during malaria attacks have been proposed for use
      in diagnosis or to assess the severity of the disease. In order to analyse the
      plasma levels of cholesterol, triglycerides, HDL-C et LDL-C, we compared, in an
      endemic area (Sao Tome island), two groups of patients children infected with
      Plasmodium falciparum (simple malaria attack and cerebral malaria) with a control
      group of asymptomatic children. No correlation between lipid plasma levels and
      disease severity was found. Correlations between lipids and parasitemia or anemia
      were analysed. The mechanism of plasma lipid changes during attack are discussed.

PMID- 9033911
TI  - Dendritic leucocytes as possible carriers of murine Plasmodium merozoites.
      Preliminary note.

PMID- 9033912
TI  - Improvement of blood and fly gut processing for PCR diagnosis of trypanosomosis.
AB  - We have adapted a simple and efficient technique to detect trypanosomes in human
      blood, without DNA purification, and increased the sensitivity threshold to 1
      parasite in 1 ml. We have then applied it for detection of parasites in midguts
      of tsetse flies, negative by microscopy. This technique has been developed for
      field conditions and could greatly facilitate epidemiological studies.

PMID- 9033913
TI  - Detection by polymerase chain reaction of Trichinella spiralis larvae in blood of
      infected patients.

PMID- 9033914
TI  - Factors associated with microsporidial and cryptosporidial diarrhea in HIV
      infected patients.
AB  - Cryptosporidium and microsporidia are increasingly recognized as important agents
      of chronic diarrhea in human immunodeficiency virus (HIV) infected patients.
      These protozoa present clinical and biological similarities but coinfection with
      these two parasites seems uncommon in a population of diarrheic HIV infected
      patients in the Paris area (France), a comparison study was performed in order to
      clarify epidemiological differences between these protozoa. From November 1993 to
      December 1994, 26 microsporidial infected patients were compared to 28
      cryptosporidial patients for various factors. Results of a multivariate logistic
      regression analysis showed that trips to tropical countries remained strongly
      associated with microsporidic compared with Cryptosporidium adjusted odds ratio
      [OR] = 4.6, 95% confidence interval [CI] 1.1-19.5). Thus, as compared with
      cryptosporidiosis, specific epidemiological factors could be associated with
      microsporidial transmission in tropical countries.

PMID- 9033916
TI  - [Kinetics of antibiotic distribution in the bronchopulmonary area].

PMID- 9033917
TI  - [Lower respiratory infections: predictive factors of therapeutic response].

PMID- 9033918
TI  - [Intracellular pharmacokinetics and pharmacodynamics of antibiotics].

PMID- 9033920
TI  - [Is there a place for psychology in a scientific medical journal?].

PMID- 9033919
TI  - [Efficacy of a 5-day treatment with an azalide (azithromycin) in superinfections
      of chronic bronchitis].

PMID- 9033921
TI  - [Passive smoking and bronchial cancer: a difficult relation to establish].
AB  - There is a certain controversy over whether there is a relationship between
      passive smoking and bronchogenic cancer. The first epidemiology studies has found
      a small increase in the relative risk. Experimental work in animals have
      demonstrated that the smoke produced by a burning cigarette contains more
      cancerogenic agents than the smoke inhaled by a smoker. In man where only
      epidemiology studies are possible, the problem lies in quantifying exposure to
      passive smoking. Questionnaires or assay of markers such as CO and HbCO,
      thiocyanates, nicotine and its metabolite cotinine and certain adduits have been
      used. There are many possibilities for bias in such studies including
      classification of smokers among non-smokers, confounding factors (age,
      profession, eating habits), subjects' memory, and data collection errors. Meta
      analyses have attempted to overcome the lack of power in many studies. Some of
      these meta-analyses have used correction factors to take into account publication
      bias. Meta-analyses have led to the conclusion that the risk for women exposed to
      their husband's tobacco smoke is somewhat increased compared with a non-smoking
      non-exposed population. The relative risk is about 2-fold higher and has been
      observed in Greece. The existence of a dose-intensity relationship has not been
      confirmed. Likewise, it is impossible to conclude concerning the role of passive
      smoking in children due to the small amount of data available.

PMID- 9033922
TI  - [Extensive psychological study in managing patients with asthma].
AB  - Extensive psychological investigation was proposed to 20 adults hospitalized in
      an emergency setting for severe acute asthma. The investigations demonstrated the
      various personality organizations in these patients and the complexity of
      external and internal factors participating in triggering asthma which then
      constitutes a supplementary element the patients must deal with. The data
      collected were divided into a small number of basic categories according to the
      nature of the spontaneous relationship, the quality of the mental functions or
      the overall psychosomatic economy, yielding prognostic value and information to
      formulate and adjust management decisions.

PMID- 9033923
TI  - [Explanatory factors of length of stay at the diagnosis-related group 129: common
      pneumonia and pleurisy, aged over 69 and/or associated co-morbidities].
AB  - BACKGROUND: Utilization of diagnosis related groups (DRGs) for hospital
      comparison, based on length of stay (LOS). OBJECTIVES: Inside a DRG (Pneumonia
      and pleurisy > 69 and/or associated comorbidities), to point out the explicative
      factors of LOS and the variables which could be recorded for a better description
      of these patients. SETTING: Pneumologic unit of Limoges' teaching hospital.
      METHODS: From 01-01-94 to 31-12-94, the DRG 129 was studied through the medical
      unit summary, the performance status at entrance, the social complexity, the
      characteristics of pneumonia (symptoms, temperature, arterial pressure...), the
      severity by American Thoracic Society (ATS) criteria, the procedures (chest X
      ray, biology, fibroscopy...), the antibiotic treatments (intravenous and oral).
      Statistical tests associated univariate analysis, linear and logistic
      regressions. RESULTS: LOS was 15.53 d +/- 8.57 (m +/- SD). The mathematical model
      explains 69% of the variance of LOS logarithm. The logistic regression found 5
      variables with a significant odds-ratio (OR) for an increased LOS: a high ATS
      score, repeated laboratory tests, a complex social situation, an increase length
      of antibiotic treatment (intravenous and oral). CONCLUSION: A better description
      of LOS, inside a DRG, needs supplementary variables. For pneumonia admitted in
      Limoges' hospital, the severity of the disease, the number of laboratory tests,
      the antibiotic treatment, the social complexity are the more significant
      indicators.

PMID- 9033924
TI  - [Postpneumonectomy pulmonary edema. Review of the literature. Apropos of 2 new
      cases].
AB  - Postpneumonectomy pulmonary edema is a poorly understood clinical entity. We
      report two new cases and review the literature. The main manifestations are
      increased pulmonary perfusion flow, endothelial damage, and amputation of the
      lymphatic system. Treatment depends on the physiological situation of the lung
      remaining after pneumonectomy. Prevention requires co-operation between the
      medical and surgical teams.

PMID- 9033925
TI  - [Localized pulmonary opacities detected by x-ray computed tomography].

PMID- 9033927
TI  - [Gastric metastasis of epidermoid cancer of the trachea].

PMID- 9033926
TI  - [Synchronous bronchial cancers disclosed by Pierre Marie Bamberger syndrome and
      Schwartz-Bartter syndrome].

PMID- 9033928
TI  - [How to detect, correct and prevent tissue hypoxia in patients in intensive care
      units. 3rd European Consensus Conference on Resuscitation. Versailles, 7-8
      December 1995].

PMID- 9033929
TI  - [Clinical aspects and diagnosis of sulfite intolerance. Apropos of 9 patients].
AB  - We performed an oral tolerance test for potassium metabisulfite in 33 patients
      and discovered sulfite intolerance in 9. These 9 patients had rhinitis including
      7 with asthma. Alcoholic beverages, especially champagne, were the triggering
      factors the most frequently found for respiratory manifestations. Alcoholic
      beverages triggered bronchial or nasal reactions in 7 patients out of 9 (rhinitis
      in 7, asthma in 2). As in a large number of published cases, sulfite intolerance
      was evidenced by respiratory manifestations in our patients. Exceptional
      anaphylactic reactions have also been reported. Respiratory intolerance to
      sulfites in uncommon. A nasal or bronchial reaction occurring within minutes
      following ingestion of alcoholic beverages is highly suggestive of sulfite
      intolerance as is the development of acute asthma after administration of sulfite
      containing drugs. Diagnosis is confirmed by oral tolerance tests versus placebo.
      The only effective preventive measure is to eliminate food and drugs containing
      sulfites. Such measures are justified to prevent acute episodes of asthma.

PMID- 9033930
TI  - [Endobronchial lipomas. Apropos of 4 cases].
AB  - We present 4 cases of endobronchial lipomas observed in our department over the
      last fifteen years. Histological diagnosis was obtained in all cases after
      endobronchoscopy and biopsy. Endobronchial exeresis was possible in one patient,
      lobectomy was required in a second. For the other two patients, surgery was not
      performed due to the patient's age and the small size of the tumor. Radiography,
      bronchoscopy and computed tomography findings suggested the diagnosis which was
      confirmed at pathology examination of the biopsy or surgical specimen. Treatment
      for endobronchial lipoma should be as conservative as possible either by
      endobronchial or laser resection. Thoracotomy should only be used when bronchial
      or pulmonary alterations are irreversible.

PMID- 9033931
TI  - [Symptoms and life of patients with chronic bronchitis. Preliminary results].
AB  - Improvement in the bronchial obstruction is the aim of treatment for patients
      with chronic bronchitis. In this work, we attempted to identify subjective
      psychosocial and neurophysiological factors which are essential for understanding
      the quality of life in these patients. The study included 77 male patients under
      80 years of age who were diagnosed as having chronic bronchitis by their family
      physician. In all cases, the disease state was stable without any other
      complication or co-morbidity. Each patient responded to a questionnaire and
      underwent volume-flow tests. The population was divided into 2 groups by VEMS:
      VEMS > or = 50% (n = 48) and VEMS < 50 (n = 19). Main component analysis followed
      by varimax rotation was used to analyse data. A Cronbach coefficient was
      calculated to measure data skewness. The Pearson correlations were calculated for
      the different factors. Mean intergroup means were compared with the unpaired t
      test. Data analysis demonstrated two physical factors: dyspnea and bronchial
      obstruction; 4 psychological factors: anxiety, impotency/hopeless feeling,
      depression, fatigue: and one psychological trait. Key symptoms of chronic
      bronchitis developed in patients with affective states contributing to the
      patient's subjective description of his disease and influencing therapeutic
      management. A better understanding of these patients is needed to improve
      treatment of chronic bronchitis.

PMID- 9033932
TI  - [Uncommon site of Bergeyella zoohelcum. Apropos of a case].
AB  - Bergeyella zoohelcum is a Gram negative bacillus which can be found in several
      pathological localizations in man: leg abscesses, septicemia, meningitis. We
      observed a case of community-acquired pneumonia caused by Bergeyella zoohelcum.
      On history taking it was found that the patient was exposed to a dog which may
      have been the carrier of the Gram negative bacilli. The clinical course was long,
      one year, with persistent excavation.

PMID- 9033933
TI  - [Rare etiology of multiple pulmonary lacunae].
AB  - Sarcoma of the common pulmonary artery are rare malignant tumors which can mimic
      pulmonary embolism. In the case presented here, the inaugural signs were
      particularly misleading: multiple pulmonary lacunae on computed tomography. The
      unusual aspect and asymmetric localizations at pulmonary angiography then
      suggested the doubtful nature of the embolism etiology. Magnetic resonance
      imaging findings suggested the diagnosis of sarcoma of the pulmonary artery.
      Certain diagnosis was obtained at pathology examination of the surgical specimen
      after thoracotomy. A malignant fibrous histiocytoma was identified. Curative
      resection was not possible and chemotherapy was performed. Unusual parenchymal
      lesions were then evidenced on the radiography. Better and better magnetic
      resonance imaging criteria are described in the literature and help distinguish
      between thromboembolism and sarcoma of the pulmonary artery. Follow-up of the
      clinical course is thus improved. It is nevertheless necessary to evaluate
      intravascular extension to determine whether curative surgery is possible.

PMID- 9033934
TI  - [Tuberculous pleurisy followed by bronchial cancer in a patient with HIV
      infection].
AB  - Both clinical and radiologic manifestations can have unusual figures in patients
      with acquired immunodeficiency syndrome (AIDS). Infectious involvement, as in
      particularly tuberculosis, may simulate a neoplasm, and vice versa. We report a
      case of a tubercular pleuresy followed 14 months later by a lung cancer in a
      patient infected with the human immunodeficiency virus (HIV). This observation
      pose the delicate diagnostic problem of a recurred endobronchial tuberculosis we
      describe the chest roentgenograms and the computed tomography-scans patterns. We
      give the place of both of them. We call attention to the valuable role of the
      endobronchial endoscopy in the differential diagnosis between a recurrence of the
      tuberculosis or a lung cancer. This case demonstrate quite well that thoracic
      complications in AIDS are multiple and can be variable in the course of the
      disease. That command a definite exploration for an appropriate diagnosis and
      treatment.

PMID- 9033935
TI  - [Severe febrile pneumopathy, a diagnostic and therapeutic emergency].

PMID- 9033936
TI  - [A rare occupational disease: pneumomediastinum].

PMID- 9033937
TI  - [Bronchocele and hemorrhagic rectocolitis: fortuitous association?].

PMID- 9033938
TI  - [Eosinophilic pleuropneumopathy in hemorrhagic rectocolitis].

PMID- 9033939
TI  - [Retinoids and glial tumors. A new therapeutic approach?].

PMID- 9033940
TI  - [Neuro-cognitive models of spelling and Alzheimer disease: mutual clarification].
AB  - The neuro-cognitive models developed over the last twenty years have considerably
      added to the understanding of disorders of spelling and writing resulting from
      brain lesions. These models differentiate between central processes, damage to
      which explains linguistic disorders, and peripheral processes, damage to which
      results in praxia and related disorders. This article analyses studies which have
      applied these distinctions to disorders observed in Alzheimer's disease. This
      disease causes unusual pathological situations which show certain types of
      agraphia rarely seen in the relevant literature, particularly certain peripheral
      forms. Several studies considered demonstrate the frequency of lexical agraphia
      in Alzheimer's disease. These lexical disorders of written expression seem to be
      independent of the lexico-semantic disorders found in other areas of the
      intellectual processes, Central writing disorders-lexical but also phonological
      would appear to be the result of relatively focussed dysfunctionings, the left
      gyrus angularis and left gyrus supramarginalis respectively, as is suggested in
      brain metabolism studies. Moreover, certain patients develop peripheral writing
      disorders which are at present less well known, on a cognitive and
      neurobiological point of view. Inferences from other pathological contexts
      reveals that these disorders are often associated with diffuse cerebral lesions.
      Therefore disorders of written expression in Alzheimer's disease may be the
      result of two different pathological mechanisms: central disorders arising from
      localized areas of dysfunctioning at the left temporo-parietal intersection;
      peripheral disorders linked to the dysfunctioning of a much wider network
      involving the parietal and frontal regions of both cerebral hemispheres. To
      account for the diversity of clinical pictures, we suggest a physiopathological
      hypothesis which could also be used as a therapeutic model in Alzheimer's
      disease.

PMID- 9033941
TI  - [2 cases of frontal dementia with non-specific histological lesions: clinico
      pathological and nosological discussion].
AB  - We report two cases of "frontal lobe dementia", patho-anatomically defined by non
      specific as neuronal loss, gliosis and spongosis. The review of the literature
      permit to discuss the clinical picture of "fronto-temporal dementia" in regard to
      neuropathological basis. Further, the boundaries with Pick's disease, Kraepelin
      disease, subcortical gliosis and the "prions diseases" are considered. Without
      more precise nosological status, tacking in count the great variability of the
      clinical signs, we can concluded that, at present time, the term of frontal type
      dementia with "non-specific histological features", that underlines the
      neuropathological characteristics is the most appropriate to define this clinico
      pathological entity.

PMID- 9033942
TI  - [Analysis and course of cognitive deficits after rupture of aneurysms of the
      anterior communicating artery].
AB  - The aim of this study is to investigate general intellectual and memory
      performances at the secondary (3 weeks to 4.5 months) and late (10 to 16 months)
      stages following rupture of anterior communicating artery aneurysms (AACA).
      Twenty one patients presenting with selective lesion within frontal, or
      cingulate, callosal, caudate, basal forebrain areas were evaluated. At the
      secondary stage, the analysis of the general intellectual capacities revealed a
      drop of performance, prominent on performance IQ, which was more severe than the
      learning deficit. Specific cognitive evaluations revealed increase of the
      execution time, but performance was relatively preserved: in the Stroop test,
      focused attention disorder was moderate: the modified Wisconsin Card Sorting test
      was correctly performed in most cases; significant deficits of verbal short-term
      memory, long-term verbal and visuo-spatial learning, and access to semantic
      memory were observed. At the late stage, general intellectual performance
      improved, but did not reached the estimated prelesional level in most cases;
      specific cognitive disorders had most often disappeared. Most performances were
      best explained by the severity of lesions in the left cingulate cortex and corpus
      callosum area. These results show that the cognitive profile of AACA patients is
      different from classical descriptions of the "amnesic syndrome", and is also
      different at the secondary and late stages; this evolution has to be taken into
      account in studies describing cognitive deficits of such patients, or comparing
      them with others presenting with "annesic syndrome".

PMID- 9033944
TI  - [Arachnoid cysts and subdural hematomas].
AB  - Arachnoid cysts of the middle cerebral fossa is a not uncommon lesion which can
      occur in young subjects, sometimes after minimal head trauma. Subdural hematomas
      and sometimes intracystic hemorrhage may develop. We report a personal series of
      seven cases seen in young subjects (6-24 years). Clinical presentation was not
      specific, the complication usually being revealed by signs of intracranial
      hypertension. The pathogenesis of subdural hematoma is discussed. Magnetic
      resonance imaging is the most useful diagnostic tool, providing excellent tissue
      specificity, although CT scan is often used to visualize a subdural hematoma and
      subsequent arachnoid cyst. Treatment relies on surgery to empty the subdural
      hematoma and remove compression. There has been no real consensus on treatment
      modalities. Long-term prognosis is good in most cases.

PMID- 9033943
TI  - [Peripheral nerve and spinal cord complication in intravenous heroin addiction].
AB  - The neurological complications observed in 6 HIV negative intravenous drug users
      are reported. Four developed acute neuromuscular involvement in a lumbosacral or
      brachial distribution with rhabdomyolysis, myoglobinuria, hypovolemia, renal and
      hepatic failure in the 3 most severely affected patients. Despite evidence of
      immunologic abnormalities and especially presence of anti-heroin antibodies, we
      feel that causative mechanisms include mixed compression and ischemia with an
      underlying toxic myopathy, resulting in segmental myopathy with secondary
      compression of peripheral nerves. Two patients developed myelopathy with acute or
      chronic onset. The mechanisms were vascular with spinal cord infarction in the
      acute form and probably infectious with secondary compressive arachnoiditis in
      the chronic form. In these 2 patients with myelopathy, outcome was poor.

PMID- 9033945
TI  - [Crossed aphasia disclosed by central auditory disorder].
AB  - A 80-year-old woman, right-handed, suddenly felt the impression to be deaf.
      Besides, she presented language disorders of aphasic type relating to a sensorial
      transcortical aphasia. The case meets the diagnostic criteria for crossed
      aphasia. The magnetic resonance imaging showed a right temporo-parietal infarct.
      There was no sensorial or peripheral auditive disorder and no auditory agnosia of
      non verbal modality. During the evolution, the aphasic symptoms diminished
      partially and the subjective auditory deficit of the left ear continued. The
      integrated auditory evaluation (neuroacoustic test, study of auditory gnosia,
      dichotic listening test, evoked cortical auditory potentials) allowed the
      evidence of the characteristic disturbances of a right hemianacousia: loss of
      left hear in dichotic audition, decrease of amplitude of evoked right cortical
      auditory potentials. In the light of theories concerning auditory integration,
      one can explain this evolution. The initial aphasic comprehension disturbance
      expresses the alteration of the linguistic treatment of auditory information of
      the dominant hemisphere, here the right hemisphere. Subsequently, the linguistic
      disturbance regresses largely, letting persist the change of general auditory
      treatment. The representation of this general auditory treatment is hemispheric
      bilateral, the only right hemispheric damage shall result in hemianacousia.

PMID- 9033946
TI  - [Cerebral thrombotic complications, arterial and venous, disclosing inflammatory
      bowel disease].
AB  - A 40 year old woman presented successively an arterial and a venous cerebral
      thrombosis, revealing an inflammatory bowel disease. Digestive manifestations
      were very poor until then. Stroke is a rare complication of inflammatory bowel
      disease, and is usually correlated with and active phase of the disease. The
      mechanism by which the thrombogenic process occurs is unclear. The possible
      prothrombotic role of hemostasis disorders and the role of an angiitic process
      are discussed.

PMID- 9033947
TI  - [Treatment of juvenile myoclonic epilepsy with low-dose sodium valproate].
AB  - Eleven patients with Juvenile Myoclonic Epilepsy were treated using small doses
      of a sustained-release form of valproic acid (500 mg/day). This treatment has
      lasted for an average of 33 months (8-69) and has been continued in all of the
      patients. None of them has experienced a new generalized tonic-clonic seizure.
      The myoclonias have become considerably less frequent and less intense. No side
      effects have been spontaneously reported by the group of patients. Thus, we
      suggest to start newly diagnosed patients on small doses of valproic acid.

PMID- 9033948
TI  - [Conference at the Salpetriere. 1995 January. Progressive multifocal cerebral
      involvement in a 70-year-old woman].

PMID- 9033949
TI  - [Laterobulbar infarction].

PMID- 9033950
TI  - [Periodic palsies and myotonias are ion channel diseases].

PMID- 9033951
TI  - [Central nervous system infections in patients with malignant diseases].
AB  - Infections of the nervous system remain a significant source of morbidity and
      mortality in patients with cancer. This paper reviews the main pathogens and
      emphasizes some of the principles of diagnosis and management of nervous system
      infections in cancer patients. Due to immunosuppression, diagnosis is more
      difficult in this group, secondary to the multitude of potential pathogens, and
      often by their atypical presentations. Fever or headache are often the only
      symptoms. Clinical history and general examination should guide appropriate
      studies such as neuroimaging. CSF analysis, cultures, and brain biopsy.
      Diagnostic evaluation should be pursued rapidly and aggressively since specific
      treatments can often reduce morbidity and mortality. Bacterial infections are
      generally due to break-down of the natural barriers and neutropenia. In
      neutropenia, Pseudomonas aeruginosa, and Enterobacteriae are the most frequent
      etiology. If all causes of immunodepression are included, Listeria monocytogenes
      meningitis is the main bacterial infection encountered. Fungal infections have
      emerged as a major cause of death among cancer patients. The prognosis of
      cryptococcosis and histoplasmosis meningitis are markedly improved with new
      antifungal therapy. Aspergillosis and Mucormycosis, which may cause cerebral
      abcesses and secondary vascular complications, are almost always fatal. The
      incidence of meningo-cerebral Candidiasis is often underestimated. Similar to
      Histoplasmosis, it is frequently disseminated. Viral infections are mainly seen
      in patients with T-lymphocyte defects. Herpes-simplex virus and Varicella-Zoster
      virus encephalitis should quicky lead to intravenous treatment with Acyclovir. As
      in AIDS patients, cerebral toxoplasmosis is the most frequent parasitic infection
      and appropriate therapy greatly reduces morbidity. It should be emphasized that
      multitude pathogens are often seen in cancer patients. Despite development of new
      therapeutic agents, central nervous system infections should still be considered
      life-threatening. Therefore, antibacterial, antifungal, and antiviral prophylaxis
      should be the rule for all cancer patients.

PMID- 9033952
TI  - [Edouard Claparede and human memory].
AB  - The Genevan neurologist and psychologist Edouard Claparede is not well enough
      known to present-day neuropsychologists However, at the beginning of the century
      he developed certain modern concepts by introducing the notions of "implicit" and
      "explicit" into the study of memory. Edouard Claparede applied the saving method
      in relearning, initiated by Ebbinghaus, in the assessment of abilities retained
      by patients suffering from Korsakoff's syndrome. He described the two implicit
      memory phenomena which are today called "priming effects" and "skill learning".
      Edouard Claparede also showed the influence of the implicit and explicit memories
      in recognition. His approach places him in the tradition of the multisystem
      theories of the memory: he made a distinction between habits and memories and
      then integrated the idea of familiar knowledge in this architecture of the
      memory, which is very close to that of Tulving (1985). Moreover, the importance
      that he gaves to perceptive data in recognition and the self in voluntary recall
      bring to mind the more recent distinction between data-driven and concept-driven
      processes in functional theories of memory. This integration of the two
      approaches, the structural and functional, must place Edouard Claparede among the
      most important precursors of the theories of human memory.

PMID- 9033953
TI  - [Spontaneous intracranial hypotension syndrome].
AB  - Spontaneous intracranial hypotension is a rare but well known entity first
      described by the German neurosurgeon Schaltenbrand. We report the clinical and
      radiological findings of four patients (2 males, 2 females, mean age 55 years)
      presenting with this clinical entity and peculiar constant MRI findings. Intense
      postural headache was present in all patients together with a very low CSF
      pressure at lumbar tap although none of the patients had any history of recent
      lumbar puncture, spinal or cerebral surgery or cranio-cervical trauma. MRI
      revealed in all patients an intense meningeal enhancement and thickening which
      was most prominent on the dural side of the subdural space. The ventricular
      system was thin, presenting almost like slit ventricules. A downward shift of the
      cerebellar tonsils and hemorrhagic subdural collections were also observed in two
      patients. Biopsy of meninges performed in two patients showed fibrosis of the
      leptomeninges together with signs of old hemorrhage in one case. We postulate
      that histologic and radiologic changes are due to chronic subdural bleeding in
      relation with abnormal displacement of the nervous structures due to intracranial
      hypotension. The underlying cause of spontaneous intracranial hypotension is
      rarely established and the course of the disease is benign. Some authors have
      advocated to perform isotopic cysternography in search for a CSF leak,
      particularly in the spine, that could be surgically corrected. No such
      investigation has been conducted yet in our patients because the spontaneous
      evolution has been mostly favorable.

PMID- 9033954
TI  - [Hemichorea and striatal infarction].
AB  - We present two cases of hemichorea associated with an arterial ischaemic stroke
      in the controlateral striatum and we reviewed 28 similar cases in the literature.
      The pathogenesis of this movement disorder involves the gabaergic and
      enkephalinergic neurons of the striatal matrice which mainly projects on the
      external globus pallidus. A destruction of the striatal neurons of the indirect
      striato-thalamo-cortical ways may reduce their inhibitory out flow on normal
      inhibited thalamic and cortical structures and then create abnormal choreiform
      movements. The scarcity of this phenomenon can be explained by: 1) the
      repartition of the enkephalinergic local circuit neurons which represent but one
      third of the motor striatal neuronal population; 2) the type of vascularisation
      which often involves larger territories in the striatum and the globus pallidus
      or the anterior limb of the internal capsule. These abnormal movements are often
      transient because of the regulation of accessory striato-nigro-striatal, cortico
      striato-nigro-thalamo-cortical and cortico-luysin circuits. More over, because
      these hypotheses and after having reviewed all such cases in literature, choreic
      movements to pure thalamic involvement are to be questioned.

PMID- 9033955
TI  - [Sympathetic skin responses and variability of the R-R interval: correlation with
      the severity stages of diabetic polyneuropathy].
AB  - The sympathetic skin responses (SSR) and the variations of the R-R interval of
      the electrocardiogram (the difference between the maximum and minimum heart rates
      at rest, the ratio between the maximum and minimum heart rates during the
      Valsalva manoeuvre or Valsalva ratio, and during an active orthostatic test or
      orthostatic ratio) have been measured in 32 control subjects and 53 diabetic
      patients. These latter ones were classified according to the existence and the
      increasing severity of a polyneuropathy (PNP) into 4 grades (0 to III) based on
      Dyck's classification modified depending on the presence or the absence of
      cutaneous impairments in grade II. There was an important inter-individual
      variability for SSR as well as R-R interval results, in the control group. In the
      absence of PNP, the vegetative tests showed normal values. These tests were
      severely degraded in the diabetic patients with a PNP grade III, ov even could
      not be performed. The SSR amplitude was decreased in all diabetic patients. In
      the presence of clinical signs of dysautonomia, the SSR amplitude, the heart rate
      variability at rest and the orthostatic ratio were significantly different from
      those of the control subjects. The presence of trophic disorders appearing at PNP
      grade II did not significantly modify the results of the tests. Although they did
      not allow any differentiation of the PNP intermediary grades. SSR and R-R
      intervals are of interest in appreciating the infra-clinical existence and the
      importance of the neurovegetative disorders occurring during diabetic
      polyneuropathies.

PMID- 9033956
TI  - [Pasteur's neurologic disease].
AB  - Based on Pasteur's own documents and studies devoted to him, we reconstruct the
      clinical presentation of his disease. At the age of 46, Pasteur suffered a left
      hemiplegia, probably with definitive dequellae related to a cavernoma. Ten years
      later, he developed signs of disturbed expression then a pseudo-bulbar syndrome.
      Possible causes are discussed.

PMID- 9033957
TI  - [Neurologic complications in a case of Werner syndrome].
AB  - A 39 year old caucasian man was admitted in 1994 to the neurological department
      with a left pure motor hemiplegia that appeared suddenly. This patient showed
      typical features of Werner's syndrome. He had a hoarse voice, a diffuse muscle
      weakness and atrophy in the upper and lower limbs with chronic ulcers on the
      legs. His scalp and public hair were sparse. Cranial MRI revealed several lesions
      in the white matter, low signal intensity on T1 weighted images and high signal
      on T2 weighted images. Cerebrospinal fluid (CSF was inflammatory with
      hypercytosis and proteinorachia was 0.50 g/l with synthesis of IgG. Sural nerve
      biopsy revealed muscle atrophy and the loss of myelinated fibers. Thus, central
      and peripheral nervous systems were affected in this case.

PMID- 9033958
TI  - Waldenstrom's macroglobulinemia associated with glioblastoma. A case report.
AB  - Waldenstrom Macroglobulinemia (WM) involves the Central Nervous System in about
      10% of the affected patients, but only occasionally related clinical and
      histopathological changes have been considered. Most of the published papers
      focus on leptomeningeal lymphoplasmacytic infiltrates, even though the damage to
      the CNS results in a more variegated scenario. Association to a malignant
      neoplasm, usually of lymphoid series, is not uncommon, instead association with a
      glioblastoma is rare, and only 3 cases have been reported. Despite the rarity of
      this finding, the association Waldenstrom Macroglobulinemia-glioblastoma may not
      be coincidental. Probable etiopathological links are thereby discussed.

PMID- 9033959
TI  - [Cytomegalovirus encephalitis in an immunocompetent adult].
AB  - Cytomegalovirus encephalitis in immunologically normal patients is rarely
      reported in the literature. Only seven cases have been previously reported. CMV
      infection was diagnosed in a 24-year-old, immunologically normal female
      presenting a severe clinical picture due to encephalitis. Diagnosis was based on
      detection of CMV DNA in the CSF with the polymerase chain reaction.
      Administration of ganciclovir was followed by an immediate improvement.

PMID- 9033961
TI  - In celebrating the 158th anniversary of lacuna cerebri.

PMID- 9033960
TI  - [Familial epilepsy seizure disclosing long QT syndrome].
AB  - The Romano-Ward syndrome shows a congenital prolonged QT on the
      electrocardiogram. It is often revealed by syncopes, sudden death and, in rare
      cases, by an epileptic attack. We report the cases of two sisters presenting this
      syndrome. One of them presented an inaugural epileptic attack. The
      electrocardiogram returned to normal and the seizures disappeared after a
      treatment with beta-bloquants.

PMID- 9033963
TI  - Effects of prolonged glucose stimulation on pancreatic beta cells: from increased
      sensitivity to desensitization.
AB  - The prolonged exposure of pancreatic islets and isolated beta cells to elevated
      glucose concentrations induces a state of unresponsiveness to glucose
      (desensitization). However, an increased sensitivity to glucose (detected by a
      shift to the left of the dose-response curve of glucose-induced insulin release)
      has been also reported after chronic exposure to glucose, making the overall
      response less comprehensible. In vitro models have many theoretical and practical
      advantages in better understanding the effects of the prolonged glucose
      stimulation; moreover, they are also suitable for studying the mechanisms
      responsible of the observed alterations. We have performed a time-course study of
      the effect of the exposure to glucose at high concentration on the secretory
      behaviour of beta cells. Rat pancreatic islets exposed for 30 min to high glucose
      (300 mg/dl) showed increased basal insulin secretion (175 +/- 29 vs 44 +/- 8
      pg/islet (per 30 min; n = 5, P < 0.002) was the only difference from control
      islets (exposed to 100 mg/dl). After 3 h exposure to high glucose, also increased
      sensitivity to glucose was observed, as indicated by a shift to the left of the
      glucose dose-response curve (EC50 123 +/- 10 and 177 +/- 11 mg/dl, respectively;
      n = 5, P < 0.05). After 6 h exposure to high glucose, besides the two alterations
      already described, also a decrease in glucose-induced insulin release was
      observed (688 +/- 104 vs 1184 +/- 34 pg/islet per 30 min; n = 5, P < 0.01). We
      studied the mechanism responsible for these alterations and we found that the
      "supersensitivity" to glucose may be related to alterations in the "glucose
      sensing" mechanism of beta cells, in particular in glucose phosphorylation. In
      contrast, in islets desensitized to glucose our data suggest that ion flux and
      consequent membrane potential changes play a key role in determining the
      secretory defect. Since a normal response to glyburide was observed, a proximal
      signal defect for closure of potassium channels is more likely than an intrinsic
      defect in the channel. In conclusion, our data show what the prolonged
      stimulation of beta cells with glucose at high concentration induces a series of
      distinct secretory abnormalities, with a pattern of response that leads first to
      increased sensitivity and then to decreased responsiveness to glucose.

PMID- 9033962
TI  - Non-HLA genes and the susceptibility to insulin dependent diabetes: the role of
      the CTLA-4 gene.

PMID- 9033964
TI  - Pathophysiology of non-insulin-dependent diabetes and the search for candidate
      genes: dangerous liaisons?

PMID- 9033967
TI  - Pancreas size and insulin secretion: lack of association in non-diabetic
      subjects.
AB  - Both type 1 and type 2 diabetes mellitus are associated with reduced pancreatic
      size. This could be caused by insulinopenia with loss of a trophic insulin effect
      and/or other factors associated with a diabetic state. To investigate the role of
      long-term moderate insulinemia per se, we compared the pancreatic size in healthy
      subjects with documented low (n = 5) and high (n = 5) insulin secretion. Insulin
      responses to a glucose clamp (11 mM) procedure were threefold higher in the high
      insulin responders (HIR) than low insulin responders (LIR). Age, body mass index
      (BMI), and blood glucose were similar between groups. Computed tomography showed
      no difference in total pancreatic size (total pancreas volume 84.8 +/- 29.4 ml in
      LIR, 79.8 +/- 8.4 ml in HIR; NS) nor in the size of various parts (caput, corpus,
      or cauda). We conclude that moderate hypoinsulinemia of long duration does not
      affect the pancreatic size.

PMID- 9033965
TI  - Mechanisms mediating insulin-induced hypotension in rats. A role for nitric oxide
      and autonomic mediators.
AB  - The mechanisms associated with insulin-induced cardiovascular inhibitory
      responses were evaluated in untreated normal rats and in normal rats pretreated
      with an antagonist of nitric oxide (NO) production (L-NAME), with cholinergic,
      alpha- and beta-adrenergic antagonists, or after ganglionic blockade. Male Wistar
      rats were anesthetized with a mixture of urethane and alpha-chloralose and placed
      on a electric heating pad. The femoral artery and vein were cannulated for
      measurements of mean arterial pressure (MAP), heart rate, plasma glucose, blood
      sampling, and intravenous injections. Intravenous injection of insulin (5.0 U/kg)
      in untreated rats resulted in a significant and sustained decrease in arterial
      blood pressure (average 24%) and in a slight decrease in heart rate. These
      cardiovascular responses were blocked by L-NAME and by the cholinergic antagonist
      atropine, suggesting an involvement of NO and the cholinergic receptors, or an
      effect of insulin on the central nervous system parasympathetic center. The
      ganglionic blocker hexamethonium attenuated the insulin-induced response. On the
      other hand, the hypotensive effect of insulin persisted after sympathetic
      blockade with the alpha-1 antagonist prazosin and the beta-1 antagonist atenolol.
      We conclude that the insulin-induced decrease in blood pressure is due to both
      increased cholinergic outflow and to NO production and that an enhanced
      sympathetic activity possibly mediated by a reactive release of norepinephrine or
      epinephrine modulates this response.

PMID- 9033966
TI  - Left ventricular performance and autonomic dysfunction in patients with long-term
      insulin-dependent diabetes mellitus.
AB  - Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin
      dependent mellitus type 1, affecting the sympathetic or parasympathetic sections
      or both. The different impairment in the two sections might modify left
      ventricular function early. To evaluate this relationship, we studied 61 patients
      (mean age 39.6 +/- 7 years) with type 1 diabetes for more than 10 years, without
      coronary artery disease (CAD); negative ergometric stress test) and without other
      pathologies that could interfere with ventricular function. All patients
      underwent MONO-, 2-dimensional and Doppler echocardiographic examination and
      radionuclide angiography with 99Tc (RNA). According to the outcome of the Ewing
      tests, patients were divided into two groups: group A with two or more tests
      altered (26 patients with CAN) and group B with one or no tests altered (35
      patients without CAN). No significant differences between the two groups were
      found in the systolic function parameters with either technique. In contrast, a
      pattern of abnormal relaxation was found for the diastolic function parameters:
      in group A a decrease in E-wave velocity and its time-velocity integral and an
      increase in A-wave and its time-velocity integral were detected with
      echocardiography. Moreover, RNA showed a reduced peak filling rate and an
      increased isovolumic relaxation time. When compared with normal values, an
      abnormal diastolic filling, defined as two independent echocardiography plus one
      RNA variable impairment, was found in 15 patients (57.6%) in group A and in only
      4 patients (11.4%) in group B (P < 0.001). Our findings suggest an early
      involvement of diastolic function in patients with CAN.

PMID- 9033968
TI  - Diabetologic in-service education for health professionals from non
      diabetological departments.
AB  - In order to test whether or not an in-service requalification course on diabetes
      care for health professionals (HP) of nondiabetological departments can enhance
      their level of knowledge about diabetes and the quality of care for diabetic
      inpatients admitted for reasons other than diabetes, we carried out a
      requalification course involving 171 HP (161 nurses and 10 midwives) from
      nondiabetological departments of our hospital. Areas of intervention were:
      general knowledge of diabetes (GKD), bedside monitoring of blood glucose (BMG),
      insulin preparation and administration (IPA), diagnosis and treatment of
      hypoglycemic crises (DTH), and hospitalization-related problems (HRP). HP,
      divided into groups of about 20 each, completed a basal evaluation by means of a
      25-item multiple choice questionnaire, and then attended six separate educative
      sessions, each of focusing on one topic, consisting of a theory lesson and an
      interactive exercise of equivalent length. At the end of the course, HP were re
      evaluated with the same questionnaire, and their skills in BMG, IPA and DTH were
      tested by means of specific operational checklists, which divided each complex
      operation into a sequence of single operations, and then compared them with those
      of a control group of untrained colleagues (CG). The global knowledge of diabetes
      after the courses significantly improved, as gathered from the percentages of
      correct answers in each questionnaire (61.82% +/- 23.64% vs 31.18% +/- 20.00%; P
      < 0.001); separate analysis of different areas evidenced improvements in GKD
      (72.28% +/- 12.47% vs 31.46% +/- 20.56%; P < 0.01), BMG (68.77% +/- 15.75% vs
      37.50% +/- 27.75%; P < 0.01), IPA (72.02% +/- 11.72% vs 33.45% +/- 21.22%; P <
      0.05), and DTH (90.76% +/- 6.86% vs 49.82% +/- 26.68%; P < 0.05), but not in HRP.
      Professional skills profiles of HP, evaluated by measuring the number of errors
      done performing each task, were significantly (P < 0.001) better than those of
      CG, for BMG (1.09 +/- 0.73 vs 4.91 +/- 2.01), IPA (2.36 +/- 1.64 vs 5.64 +/-
      2.25), and DHT (1.27 +/- 0.94 vs 3.82 +/- 1.12). Linear regression showed a
      significant (P < 0.001) correlation of skills and knowledge after the course for
      BMG (r2 = .49), IPA (r2 = .53), and DTH (r2 = .61). Positive although nonspecific
      indicators of outcomes of the course were the increase (of about 100%) of
      requests to our metabolic unit for diabetological consultations from other
      departments as well as the mentioning of diabetes in the diagnosis of discharge,
      and the 20% increase in the consumption of sticks for BMG. The course produced a
      significant improvement of knowledge and skills on specific diabetological items
      among participants.

PMID- 9033969
TI  - Impaired glucose tolerance and its co-variates among 2079 non-diabetic elderly
      subjects. Ten-year mortality and morbidity in the CASTEL study. CArdiovascular
      STudy in the ELderly.
AB  - This study evaluated the role of impaired glucose tolerance (IGT) as a risk
      factor in a general population of 2079 non-diabetic elderly subjects. The 10-year
      cardiovascular morbidity was similar in normal and IGT subjects. Mortality was
      greater in IGT, but the Cox equations of the hazard rate were different in
      younger and older subjects: age, sex, lung function (forced expiratory volume in
      1 s, FEV1), serum uric acid, IGT and proteinuria were predictors of overall
      mortality in the age class 65-79 years, while only the first 4 were associated
      with cardiovascular mortality. The same four items also predicted overall
      survival in subjects over 79 years old, while only age and uric acid were
      predictors of cardiovascular mortality. In older subjects, total cholesterol
      showed an inverse predictive value. Hyperuricaemia (> 6.4 mg/dl) and proteinuria
      did predict mortality in normal but not in IGT subjects, while reduced FEV1 (<
      60% theoretical) was predictive in all. In 65-79-year old subjects IGT predicted
      mortality provided that FEV1 was normal, while in those 380 years old IGT was not
      a predictor. These interrelationships should be taken into account to better
      understand the factors underlying mortality.

PMID- 9033971
TI  - Plasma neuropeptide Y in impaired glucose tolerance.
AB  - Neuropeptide Y (NPY) has been shown to be associated with insulin resistance,
      since central administration of the peptide induces muscular insulin resistance.
      NPY also occurs in pancreatic nerves and inhibits insulin secretion. In this
      study, we examined the plasma NPY levels in 10 women, aged 57-59 years, with
      impaired glucose tolerance (IGT), which is often accompanied by a combination of
      reduced insulin sensitivity and impaired insulin secretion. They were 145 +/- 4.1
      pmol/l compared with 143 +/- 4.3 pmol/l in 10 age-matched women with normal
      glucose tolerance (NGT) (NS). Furthermore, the plasma NPY did not correlate with
      fasting glucose or insulin levels, the 2-h glucose value after a 75 g oral
      glucose challenge or insulin sensitivity as determined by the euglycemic,
      hyperinsulinemic clamp technique. This suggests that plasma NPY is not altered in
      IGT.

PMID- 9033970
TI  - GAD 65 antibody but not ICA positivity in adult-onset diabetic patients is
      associated with early progression to clinical insulin dependency.
AB  - Correct classification of diabetic patients in adulthood at the time of diagnosis
      is often difficult. Some may be initially diagnosed as having non-insulin
      dependent diabetes mellitus and be treated with diet and/or oral hypoglycaemic
      agents (OHA) but later require insulin treatment. Islet cell antibodies and
      antibodies to GAD 65 have been associated with the development of insulin
      deficiency in this group of patients. In the present study, 150 patients with the
      initial diagnosis of type 2 diabetes mellitus in adulthood (30-60 years) were
      seen regularly over a period of 5 years in our diabetes outpatient clinic. Though
      treatment was started with diet or diet plus OHA, insulin therapy had to be
      introduced in a subset of patients. In all cases, serum obtained at the time of
      the initial diagnosis was analysed for islet cell antibodies and GAD 65
      antibodies, as well as for thyroid and adrenal autoantibodies as possible markers
      for polyendocrine involvement. Islet cell antibody status, body mass index and
      the presence of thyroid and adrenal autoantibodies showed no significant
      correlation to subsequent insulin requirement (< 2 years after diagnosis). In
      contrast, GAD 65 antibodies were significantly associated with the occurrence of
      clinical insulin dependency less than 2 years after the initial diagnosis (P <
      0.01), thus identifying a substantial proportion of patients requiring insulin
      therapy within the first 2 years after the diagnosis of type 2 diabetes.
      Determination of GAD 65 antibodies in patients with late-onset diabetes may
      contribute to their correct classification and adequate treatment.

PMID- 9033972
TI  - Fate of 3H- and 14C-labelled A-4166 in pancreatic islets.
AB  - The fate of 3H- and 14C-labelled A-4166 was examined in rat pancreatic islets.
      The net uptake of the meglitinide analogue by islets incubated for 60 min in the
      presence of 0.1 mM A-4166 and then submitted to repeated washes was close to 0.1
      pmol/islet. It was significantly increased when the concentration of D-glucose in
      the incubation medium was raised from 2.8 to 16.7 mM. No sizeable internalization
      of tritiated A-4166 into insulin-producing cells could be detected by
      autoradiography. These findings suggest that the interaction of A-4166 with the
      beta-cell may be restricted to its insertion on the plasma membrane and binding
      to sulphonylurea receptors.

PMID- 9033973
TI  - Diagnosis and management of sinusitis in children.

PMID- 9033974
TI  - Viral hemorrhagic fevers.

PMID- 9033975
TI  - Tularemia.

PMID- 9033976
TI  - Role of newer broad-spectrum beta-lactam and fluoroquinolone antibiotics in
      children.

PMID- 9033977
TI  - Cestode infection in children.

PMID- 9033978
TI  - Update on enterovirus infections in infants and children.

PMID- 9033979
TI  - Childhood infections with human herpesviruses types 6, 7, and 8.

PMID- 9033980
TI  - Septic shock.

PMID- 9033981
TI  - Nosocomial infections in pediatric patients.

PMID- 9033982
TI  - Antiretroviral therapy: evaluating the new era in HIV treatment.
AB  - Tools for evaluating antiretroviral therapy are still evolving. Key components
      are available such as the laboratory assays themselves, but results from these
      assays are being analyzed and presented inconsistently, making interstudy
      comparisons difficult or impossible. In part, the problems in analysis and
      presentation reflect a lack of completed clinical trials in which new laboratory
      methods such as RNA copy numbers can be validated. Survival is the clearest valid
      end point in clinical trials of antiretroviral drugs. Beyond life and death, the
      next most important issue is quality of life. Because of the difficulty in
      agreeing what "quality of life" means, and the even greater problems measuring
      such an abstract concept, in most cases assessments are made of more quantifiable
      clinical elements: cognitive and motor function, growth, and the frequency of
      opportunistic infections. Laboratory markers of disease progression are very
      quantifiable but have meaning only when they predict clinical outcome. There is a
      consensus that CD4+ counts, CD4+ percentages, and HIV copy numbers measured by
      RNA PCR are important. There is not, however, a consensus approach to
      interpretation of data from any of these markers of HIV disease, particularly
      because the interpretation may vary based on the patient's level of clinical
      disease. With time and more clinical trials with which to clarify their use,
      these tools should become more uniformly applied, at which point cross-study
      comparisons might be possible. Progress is already being made in the development
      of new antiretroviral therapies, and with improved evaluation techniques the
      evolution of new anti-HIV treatments should become an even more efficient
      process.

PMID- 9033983
TI  - Malaria in children.

PMID- 9033984
TI  - Management of otitis media in the era of managed care.

PMID- 9033997
TI  - Concordance of positive and negative symptoms in coaffected sib-pairs with
      schizophrenia.
AB  - Positive and negative symptom (NGS) dimensions were examined for their
      concordance in 46 coaffected schizophrenic sib-pairs. Results showed that the
      symptom dimensions of negative symptoms (NGS), delusion-hallucination (DHS), and
      thought disorganization (TDS) could be formulated. Discrete genetic endowment of
      these three symptom dimensions was not found as shown by the low concordance in
      sib pair analysis (kappa = 0.20-0.30). Thirty-seven pairs (80.4%) and 21 pairs
      (45.7%) had liability, defined by the presence of NGS in any one member of the
      coaffected sib-pairs, of NGS of "any degree", and of "severe degree" in 46 sib
      pairs, respectively. Both groups had high prevalence (59.1-81.0%) of positive
      symptoms. Another 9 (19.6%) and 25 (54.3%) pairs had no liability of NGS of "any
      degree" or of "severe degree" out of 46 sib-pairs, respectively. These two groups
      had high concordance (kappa = 0.45-1.00) of TDS or DHS between coaffected sib
      pairs. Based on the results, it is hypothesized that schizophrenia, as defined by
      DSM-III-R, may consist of two subtypes: one has liability of NGS and a high
      prevalence of positive symptoms, while the other has only positive symptoms.

PMID- 9033998
TI  - Psychiatric morbidity in the first-degree relatives of schizophrenic patients.
AB  - There is increasing evidence that genetic factors play a role in the etiology of
      schizophrenic disorders. One thousand eighty-nine first-degree relatives of
      schizophrenics and 1,137 controls were studied to discover their psychiatric
      morbidity. Psychiatric morbidity was found in 16.34% of the first-degree
      relatives (FDR) of schizophrenics (parents, 5.69%; siblings, 7.71%; offspring,
      2.94%) as compared to 6.9% in the controls (P < 0.001). Schizophrenia was found
      in 8.3% of the patient group, which was significantly higher (0.2%) as compared
      to the controls. Schizoid-schizotypal personality disorder was found in 3.03% of
      FDRs of the schizophrenic group. Depressive disorder was found in 4.4% and 2.1%
      in the control and patient group, respectively, which was statistically
      significant. Morbidity risk of schizophrenia was found in 16.97%, 6.22% and 5.79%
      of schizophrenia, schizoid-schizotypal personality disorder and depressive
      disorder, respectively, in the FDR of schizophrenic group.

PMID- 9033999
TI  - Comparison of the family history with the family study method: report from the
      Camberwell Collaborative Psychosis Study.
AB  - We assessed the accuracy of the family history (FH-RDC) and family study (SADS-L)
      methods for obtaining information about the presence of psychopathology in 274
      first-degree relatives of patients with psychotic disorders. The family history
      method had only modest sensitivity, 40.8% for affective disorders and 58.6% for
      psychotic disorders, but high specificity, 94.1% for affective disorders and
      98.7% for psychotic disorders. For both disorders, sensitivity was higher for
      relatives who had had previous psychiatric admissions. However, with the family
      study method, we found that relatives with affective disorder were more likely to
      be interviewed than those relatives with other disorders. Hence, the family study
      method may be prone to selection bias that distorts morbid risk estimates. We
      conclude that the best way of collecting information regarding family
      psychopathology is to interview directly as many relatives as possible and to
      collect supplementary family history information on unavailable relatives.

PMID- 9034000
TI  - Single major locus models for bipolar disorder are implausible.

PMID- 9034001
TI  - No association between schizophrenia and the serotonin receptor 5HTR2a in an
      Italian population.
AB  - A major role of the serotonergic system has been hypothesized in the pathogenesis
      of schizophrenia, mostly based on the evidence of action of new and atypical
      neuroleptics such as Risperidone or Clozapine. We evaluated the genotypes and
      alleles of the 5HT2a receptor gene in 67 nuclear families following the Haplotype
      Relative Risk (HRR) strategy and in a second sample of 100 schizophrenics and 103
      controls. The 5HT2a receptor gene polymorphism, following PCR amplification and
      subsequent Hpa II digestion, reveals a two-alleles system in the coding region of
      the gene. We did not find statistically significant differences between patients
      and controls for genotypes, nor for alleles, both in the HRR and in the case
      control groups. These results do not confirm the positive association obtained by
      Inayama et al.: [Neuropsychopharmacology 1(35): 145-219, 1994] and by Williams et
      al. [Lancet, 397:1294-1296, 1996] in our population.

PMID- 9034002
TI  - Familial spastic paraparesis: evaluation of locus heterogeneity, anticipation,
      and haplotype mapping of the SPG4 locus on the short arm of chromosome 2.
AB  - Familial spastic paraparesis (SPG) is a clinically and genetically heterogeneous
      group of disorders. At least three loci have been implicated in autosomal
      dominant pure SPG and mutations in either of two loci may cause the X-linked
      form. Although the penetrance is high for all forms by age 60, there is wide
      variation in clinical characteristics, including age of onset. Two-point and
      multi-point linkage analyses in nine families provided supportive evidence that
      the most common form of SPG is linked to chromosome 2 (SPG4). Haplotype analysis
      localized the critical region to a 6 cM interval between D2S392 and D2S367. By
      haplotype analysis, the disease in at least one family does not appear to be
      linked to any of the presently known SPG loci, suggesting that there is at least
      one additional SPG gene. Evaluation at ages of onset in 11 families gave
      suggestive evidence for anticipation with mean age of onset in parents (41.3
      years) being older than mean age of onset in children (26.9 years; P < 0.005).

PMID- 9034003
TI  - No evidence for an allelic association between schizophrenia and markers D22S278
      and D22S283.
AB  - We report a case control association study using markers D22S278 and D22S283 in
      90 unrelated patients with DSMIII-R schizophrenia and 90 controls matched for
      ethnicity, age and sex. No differences between allele frequencies for either
      marker were observed when the two groups were compared (D22S278: chi 2 = 6.53, df
      = 7, P = 0.51; D22S283: chi 2 = 14.73, df = 15, P = 0.48). These findings fail to
      support previous work by others suggesting the presence of allelic association
      between the markers D22S278 and D22S283 and schizophrenia.

PMID- 9034004
TI  - Further evidence of no association between Ser9Gly polymorphism of dopamine D3
      receptor gene and schizophrenia.
AB  - Dopamine D3 receptor (DRD3) was demonstrated to have important implications in
      schizophrenia, because it binds antipsychotic drugs and is abundant in the limbic
      system of the brain. Several groups attempted to find an association between a
      serine-to-glycine polymorphism at codon 9 of the DRD3 gene (Ser9Gly) and
      schizophrenia; however, the results were inconsistent. We conducted a case
      control association study in Han Chinese schizophrenic patients from Taiwan, to
      examine the relationship of this serine-to-glycine polymorphism and
      schizophrenia. We noted no significant differences of genotype distribution,
      allele frequencies, or homozygosity proportion of this polymorphism between
      schizophrenic patients (N = 178) and controls (N = 100). When patients were
      divided according to sex, or presence or absence of family history, the
      differences were still not significant. Our study does not support the contention
      that the Ser9Gly polymorphism of the DRD3 gene plays a major role in
      schizophrenia.

PMID- 9034005
TI  - Screening the monoamine oxidase B gene in 100 male patients with schizophrenia: a
      cluster of polymorphisms in African-Americans but lack of functionally
      significant sequence changes.
AB  - The monoamine oxidase B (MAO-B) gene was examined in 100 alleles derived from 80
      Caucasian, 10 African-American, 5 Asian, and 5 Native American male patients with
      schizophrenia to identify sequence changes that might be associated with the
      disease. Approximately 235 kb of genomic sequence, primarily in coding regions,
      were screened by dideoxy fingerprinting, a modification of single-strand
      conformational polymorphism (SSCP) analysis that detects virtually 100% of
      sequence changes [Sarkar et al. (1992): Genomics 13:441-443; Liu and Sommer
      (1994): PCR Methods Appl 4:97-108]. No sequence changes of likely functional
      significance were identified, suggesting that mutations affecting the structure
      of the MAO-B protein are uncommon in the general population and are unlikely to
      contribute significantly to the genetic predisposition to schizophrenia. Eight
      polymorphisms were identified in African-Americans and Native Americans, but none
      were identified among Caucasians. Of the eight observed polymorphisms, a set of
      five transitions and one microdeletion was identified within approximately 17 kb
      of genomic sequence in the same 3 African-American individuals, while the
      remaining 7 African-Americans had a sequence identical to that in Caucasians. The
      presence of two such haplotypes, without intermediates, is compatible with the
      hypothesis that germline mutations can occur in clusters, as also suggested by
      other recent findings.

PMID- 9034006
TI  - Exclusion of linkage between schizophrenia and the gene encoding a neutral amino
      acid glutamate/aspartate transporter, SLC1A5.
AB  - An abnormality in glutamatergic function has been hypothesized as being of
      etiological importance in schizophrenia. Twenty-three multiplex English and
      Icelandic schizophrenia families were genotyped with a polymorphic dinucleotide
      repeat sequence in the 3'-untranslated region of the glutamate/aspartate
      transporter gene called SLC1A5. Using the lod and a model-free method of linkage
      analysis (MFLINK), no evidence of linkage between SLC1A5 and schizophrenia was
      found. Our results do not support the hypothesis that SLC1A5 gene mutations or
      allelic variants provide a major gene contribution to the etiology of
      schizophrenia. However, because of the likelihood of heterogeneity of linkage in
      schizophrenia, there is a case for testing other pedigrees for linkage to the
      SLC1A5 locus. The SLC1A5 locus is one of a complex family of genes encoding
      neutral amino acid transporter proteins and the genetic relation between these
      other loci and schizophrenia has not yet been established.

PMID- 9034007
TI  - Genotypic association between dopamine transporter gene polymorphisms and
      schizophrenia.
AB  - Dopamine transporter (DAT) gene variants do not appear to provide widespread
      contributions to the etiology of schizophrenia spectrum disorders, according to
      linkage studies [Persico et al., 1995: Am J Psychiatry 152:134-136]. They may,
      however, produce modifying effects, more readily detectable in specific
      subpopulations of schizophrenics through associations analyses. We therefore
      compared polymorphic DAT gene variable number tandem repeat (VNTR) distributions
      in 84 controls and 147 patients, divided according to DSM-IIIR schizophrenia type
      criteria. No evidence of allelic association between DAT alleles and
      schizophrenia or any specific schizophrenia subtype was found. Interestingly, the
      DAT genotype distribution among schizophrenic patients did display a
      statistically significant departure from the genotype distribution found in
      controls. Such discrepancies may represent stigmata of assortative mating or may
      suggest a "modifying" contribution of homozygote DAT genotypes to pathogenetic
      processes underlying schizophrenia.

PMID- 9034008
TI  - Linkage study of the dopamine D5 receptor gene and Gilles de la Tourette
      syndrome.
AB  - A defect in the dopamine system has been hypothesized as the etiological defect
      in Gilles de la Tourette syndrome (TS). In this report, we test the hypothesis
      that the dopamine D5 receptor locus (DRD5) is linked to the genetic
      susceptibility to TS in five families studied in Canada. We tested for linkage to
      the dopamine D5 receptor gene using a microsatellite polymorphism located in the
      same cosmid clone. Using an autosomal dominant model with reduced penetrance, we
      were able to exclude linkage in four of the five families for the TS and chronic
      multiple tics (CMT) phenotype. Also, no evidence for linkage was found using
      nonparametric methods in all five families.

PMID- 9034009
TI  - Bias in the genomic distribution of CAG and CTG trinucleotide repeats.
AB  - We investigated the hypothesis that the trinucleotide repeat CAG is
      disproportionately located in exons in genomic DNA by analyzing unbiased genomic
      sequences with the Gene Recognition and Analysis Internet Link program
      (http@avalon.epm.ornl.gov/). Forty percent of CAG/CTG repeats were predicted to
      lie within exons. This is significantly greater than would be expected by chance,
      and is also greater than we have observed for ATT/AAT repeats. Therefore, our
      data support the hypothesis. Furthermore, the data support the utility of a
      recently reported CAG/CTG PCR genomic screening set for identifying pathogenic
      expanded CAG/CTG repeats.

PMID- 9034010
TI  - 5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human
      personality trait of reward dependence: interaction with dopamine D4 receptor
      (D4DR) and dopamine D3 receptor (D3DR) polymorphisms.
AB  - We recently reported an association between the long repeat allele of the
      dopamine D4 exon III receptor polymorphism and a human personality dimension,
      novelty seeking, as measured by the tridimensional personality questionnaire
      (TPQ), a personality instrument designed by Cloninger to reflect heritable facets
      of human temperament. The D4 receptor polymorphism (D4DR) accounts for only a
      small percent of the variance for this trait, suggesting that additional genes
      influence both novelty seeking as well as the other temperaments that are
      inventoried by the Cloninger TPQ. In the current investigation, we examined, in
      the original cohort of 120 normal volunteers, two additional coding region
      polymorphisms, a glycine to serine substitution in the dopamine D3 receptor
      (D3DR) and a cysteine to serine substitution in the 5-HT2C serotonin receptor
      (HTR2C). Three-way analysis of variance (TPQ score grouped by D4DR, D3DR and 5
      HT2C) demonstrated that reward dependence and persistence scores were
      significantly reduced by the presence of the less common 5-HT2Cser polymorphism.
      The effect of the serine substitution in this X-linked serotonin receptor
      polymorphism on reward dependence was also observed when male and female subject
      groups were separately analyzed. There was also a significant interaction between
      the two dopamine receptor polymorphisms and the serotonin polymorphism on reward
      dependence. In particular, the effect of the 5-HT2C polymorphism on reward
      dependence was markedly accentuated in individuals who had the long version of
      the D4DR exon III repeat polymorphism. When present in the same individual, the 5
      HT2C and dopamine receptor polymorphisms account for 30% of the observed variance
      for persistence (RD2) and 13% of the variance for reward dependence scores
      (RD134). However, the number of subjects with both less common D4DR and 5-HT2C
      polymorphisms is small, underscoring the importance of verifying this interaction
      in a larger cohort.

PMID- 9034012
TI  - Novel transcribed sequences neighbouring a translocation breakpoint associated
      with schizophrenia.
AB  - A 1.3Mb chromosome 11-specific yeast artificial chromosome (YAC) that spans a
      t(1;11) translocation breakpoint associated with major psychosis has been used to
      enrich cDNAs that are encoded within it and expressed in the human foetal brain.
      Database analysis of the selected fragments led to the identification of 54
      clones matching alpha-tubulin, 4 fragments matching two anonymous human expressed
      sequence tags (ESTs) and 8 fragments giving no database matches. The clones
      matching alpha-tubulin led to the identification of a novel alpha-tubulin locus
      located approximately 250 kb proximal to the translocation breakpoint. Extensive
      sequence and expression analysis of this locus suggests that this is a processed
      pseudogene, although a long open reading frame is maintained and the possibility
      that an abnormally acting protein may be expressed in a highly tissue or
      developmental specific manner cannot be discounted. The novel cDNA fragments map
      up to 700 kb proximal to the translocation breakpoint and are associated with
      potential CpG islands. Reverse transcriptase polymerase chain reaction (RT-PCR)
      expression analysis and high resolution genomic mapping suggest that they may
      comprise up to three novel genes. No major disruption of the identified fragments
      could be detected in the genomic DNA of translocation carriers. The psychosis
      associated with this translocation may therefore be due to position effects on
      the transcription of these genes or an involvement of translocated chromosome 1
      sequences.

PMID- 9034011
TI  - Cognitive, behavioral, and neuroanatomical assessment of two unrelated male
      children expressing FRAXE.
AB  - Standardized cognitive, behavioral, and neuroanatomical data are presented on 2
      unrelated boys with the FRAXE (FMR2) GCC expansion mutation. In the context of
      normal IQ, both boys had a history of developmental delay, including significant
      problems with communication, attention, and overactivity. Additionally, one child
      was diagnosed with autistic disorder. Data from these 2 cases are compared to
      analogous information from previous reports about individuals with the FRAXE or
      FRAXA (FMR1) mutation. These comparisons support the idea that FRAXE is
      associated with nonspecific developmental delay and possibly high-functioning
      autism.

PMID- 9034014
TI  - Human adenylyl cyclase type 7 contains polymorphic repeats in the 3' untranslated
      region: investigations of association with alcoholism.
AB  - Platelet adenylyl cyclase activity has been proposed as a trait marker for
      alcoholism [Tabakoff et al. (1988): N Engl J Med 318:134-13;9; Parsian et al.
      (1996): Alcohol Clin Exp Res 20:745-751]. Human adenylyl cyclase type 7 (ADCY7)
      is a member of the adenylyl cyclase gene family, and it may be the major form of
      adenylyl cyclase expressed in human platelets. The published cDNA sequence of
      ADCY7 indicated the presence of potentially polymorphic regions in the 3'
      untranslated region of ADCY7. PCR techniques combined with fluorescently labeled
      primers were used to amplify two separate tetranucleotide repeat regions
      [(AACA)n] in the 3' untranslated region of ADCY7 from the genomic DNA of 62
      unrelated individuals. The upstream (AACA)4-repeat was not polymorphic. Five
      different genotypes were found in the downstream (AACA)5-7 tetranucleotide repeat
      region. We also tested the association of the tetranucleotide polymorphism to
      alcohol dependence. When 30 alcoholic and 17 control individuals were compared,
      no difference was found in the ADCY7 tetranucleotide polymorphism between alcohol
      dependent and control groups. Nevertheless, to our knowledge these are the first
      polymorphisms reported in an adenylyl cyclase gene. Adenylyl cyclases are
      important receptor-G protein-coupled effectors and are involved in numerous
      neuronal functions in the central nervous system. Whether variations in ADCY7 and
      possible variations in other members of this gene family are underlying other
      psychiatric disorders remains to be studied.

PMID- 9034013
TI  - Rapid molecular haplotyping of the first exon of the human dopamine D4 receptor
      gene by heteroduplex analysis.
AB  - The dopamine D4 receptor gene (DRD4) and its products are of great interest in
      many neurospsychiatric disorders. There are at least five expressed polymorphisms
      in exons 1 and 3, plus rare expressed variants, all of which may have functional
      relevance. Several studies have described methods for studying the exon 3
      polymorphisms, especially the VNTR; fewer reports have documented the exon 1
      polymorphisms and variants of DRD4. We report here a simple, rapid, nonisotopic,
      nondenaturing heteroduplex method for determining the molecular haplotype
      composed of the two more polymorphic systems of the first exon of DRD4: the 12 bp
      duplication and 13 bp deletion. This method will facilitate future research on
      expressed variation of this gene.

PMID- 9034015
TI  - Current status of linkage for schizophrenia: polygenes of vanishingly small
      effect or multiple false positives?

PMID- 9034016
TI  - Can we find genes for schizophrenia?

PMID- 9034017
TI  - The role of meta-analysis in linkage studies of complex traits.

PMID- 9034018
TI  - Dyssynchrony, conflict, and resolution: positive contributions to infant
      development.
AB  - While most psychological research has emphasized the importance of conflict-free
      mother-infant interactions, a review of recent research suggests that
      dyssynchrony, conflict, and their successful resolution are also integral to
      normative mother-infant interactions and optimal infant outcomes. Theory and
      research incorporating these concepts are described, areas for research
      suggested, and clinical applications noted.

PMID- 9034019
TI  - Use of alcohol among lesbians: research and clinical implications.
AB  - A review of the literature on the prevalence of alcohol use and problems among
      lesbians reveals that the few studies yielding information on this population are
      beset by design and methodological problems. Those factors possibly associated
      with higher risk status of lesbians are identified, as are gaps in the
      literature, and implications for clinical practice and research are discussed.

PMID- 9034020
TI  - African-American homeless and low-income housed mothers: comparison of parenting
      practices.
AB  - The child-rearing practices of homeless and low-income housed mothers of
      preschool children in Head Start were compared. Overall, homeless mothers
      provided less learning and academic stimulation, less variety in social and
      cultural experiences, less warmth and affection, and a less positive physical
      environment for their children than did housed mothers. Mothers in both living
      arrangements provided more language stimulation to daughters than to sons.
      Implications of the findings for working with homeless families are discussed.

PMID- 9034022
TI  - Is repression adaptive? Relationships to socioemotional adjustment, academic
      performance, and self-image.
AB  - Of 74 high school students rated on a repression-sensitization continuum, the 17
      identified as "repressors" were found to have greater frustration tolerance,
      better social skills, higher educational performance, and less shy and withdrawn
      behavior when compared to the 40 identified as intermediates; they also had a
      greater sense of global self-worth and higher self-image in the scholastic and
      social content domains. The 17 students identified as "sensitizers" did not
      differ from intermediates on measures of classroom performance or self-image.
      Results are discussed in relation to earlier reports of repression as
      maladaptive.

PMID- 9034021
TI  - Predictors of depression among the elderly: racial differences over time.
AB  - Depressive symptomatology and correlates of depression were compared in 600 white
      and 600 black elderly people over a period of 18 months. Overall, factors
      associated with depression were found to be similar for both groups. They
      included prior depression; social and medical stressors; poor ego; and social
      networks that were small, with which contact was infrequent, and from which
      emotional support was lacking. Implications for intervention are offered.

PMID- 9034023
TI  - Alcohol abuse and psychopathic deviance in noncustodial parents as predictors of
      child-support payment and visitation.
AB  - In a three-stage study, noncustodial parents' psychopathic deviance and alcohol
      use accounted for significant variance in custodial parents' reports of child
      support and visitation. In noncustodial parents 'reports' compliance with child
      support, but not frequency of visitation, was related to measures of deviance.
      Implications for policy, research, and psychoeducational interventions are
      discussed.

PMID- 9034024
TI  - Distress and coping among women with HIV infection: preliminary findings from a
      multiethnic sample.
AB  - In a multiethnic sample of 53 women with HIV/AIDS, nearly 40% reported clinically
      significant levels of depression symptomatology and anxiety. Compared to a
      nonpatient norm, distress levels were higher among the Latina, African-American,
      and white women who made up the HIV sample. Prayer and rediscovery of self were
      their most frequent coping responses, suggesting that clinicians working with
      HIV/AIDS populations not overlook the importance of spiritual faith and practices
      in adapting to HIV infection.

PMID- 9034025
TI  - Early risk factors for serious antisocial behavior at age 21: a longitudinal
      community study.
AB  - Data collected over a period of 18 years were analyzed vis-a-vis risk factors for
      serious antisocial behavior in 375 young adults living in the community. Early
      aggression and hostility, acting-out behavior, academic difficulties, and
      negative family environment were identified as precursors of later deviance, and
      different patterns were found for males and females.

PMID- 9034026
TI  - Young children's social relationships with siblings and friends.
AB  - Relationships with a close friend and a younger sibling were investigated in 30
      first-born young children. Greater positive affect and reciprocity were found
      between friends than between siblings. Limited support for the consistency of
      individual differences in relationship quality across friend and sibling dyads
      was also revealed. Implications for child development and future research are
      discussed.

PMID- 9034027
TI  - Effects of legally mandated child-abuse reports on the therapeutic relationship:
      a survey of psychotherapists.
AB  - In a national survey of 907 licensed psychologists regarding mandated reporting
      of child maltreatment, predictors of outcome included: therapeutic alliance; role
      strain; therapist explicitness; family vs. individual treatment; and whether or
      not the client was the perpetrator. Therapists were asked to describe a case
      involving reporting, its impact on treatment, informed consent procedures, as
      well as their own attitudes and beliefs. Implications for research are discussed,
      and recommendations for clinical training and practice are offered.

PMID- 9034028
TI  - Emergency commitment and legislative reform in New Jersey.
AB  - The effects of a state commitment law that combines use of the dangerousness
      criterion, screening for less restrictive alternatives, and a new mental health
      structure were investigated. A time-series analysis of the number of commitments
      in a 12-year period at one screening center revealed that the expected outcome of
      the legislation--a decrease in state-hospital commitments--was not realized.

PMID- 9034029
TI  - Drug-abuse prevention efforts for young children: a review and critique of
      existing programs.
AB  - Children under age five are increasingly the target of formal interventions aimed
      at deterring subsequent drug abuse. These prevention efforts are characterized,
      however, by a lack of empirical research on the variables involved in inoculating
      very young children against later drug use, and the lack of assessments research
      demonstrating their effectiveness. Curriculum-based antidrug programs for
      preschool children are reviewed, and developmental and early intervention
      research is used as the basis of recommendations for strengthening such efforts.

PMID- 9034030
TI  - HIV-positive and AIDS-infected women: challenges and difficulties of mothering.
AB  - The impact of HIV/AIDS on the ability of 12 mothers to raise their children was
      explored. Three key themes emerged: disclosure, fear of infecting children
      through casual contact, and impact of grief. The implications of these findings
      for research and provision of services are discussed.

PMID- 9034032
TI  - On co-occurring addictive and mental disorders.

PMID- 9034033
TI  - On parents and children sleeping together.

PMID- 9034031
TI  - Conduct disorder, substance dependence, and adolescent motherhood.
AB  - Of 26 teenage mothers in a nonclinical sample, one-third were found to have a
      diagnosis of conduct disorder; of these, two-thirds were also diagnosed with
      substance abuse or dependence. Conduct disorder as a risk factor for adolescent
      pregnancy and substance use is discussed, as are the implications for preventive
      intervention.

PMID- 9034034
TI  - Expanding the biocultural synthesis toward a biology of poverty.

PMID- 9034035
TI  - Living on the edge: dietary strategies of economically impoverished women in
      Cali, Colombia.
AB  - Economically impoverished women in Cali, Colombia, have restricted access to food
      in a city where food is abundant. Ethnographic observations, interviews and 2 day
      food records were used to better understand the coping strategies used by a group
      of these women (n = 85) to maintain adequate levels of energy intake.
      Anthropometric indicators of nutritional status were normal for the group.
      Interview data revealed that the ability to purchase food was a concern for 58%
      of the women. When faced with a restricted ability to purchase food, the women
      indicated they made compromises in meal composition, reduced portion sizes,
      and/or reduced the number of meals. They also relied on relatives, friends,
      neighbors, store credit, or local government programs for access to food. Changes
      in meal composition were identified in 17.1% of all diet records (n = 509). Low
      energy intake (defined as energy intake < or = 1.27 x BMR) was identified in
      17.1% of all diet records. Carbohydrate consumption was significantly greater on
      low-energy intake days. The adequate nutritional status of this group of women
      suggests that their coping strategies are usually adequate to maintain energy
      intake, but the presence of uncertainty, the frequency of compromises in diet
      composition, and the frequency of low-energy intake days suggest that these women
      are at risk for undernutrition.

PMID- 9034036
TI  - Plasticity, political economy, and physical growth status of Guatemala Maya
      children living in the United States.
AB  - Migration of Maya refugees to the United States since the late 1970s affords the
      opportunity to study the consequences of life in a new environment on the growth
      of Maya children. The children of this study live in Indiantown, Florida, and Los
      Angeles, California. Maya children between 4 and 14 years old (n = 240) were
      measured for height, weight, fatness, and muscularity. Overall, compared with
      reference data for the United States, the Maya children are, on average, healthy
      and well nourished. They are taller and heavier and carry more fat and muscle
      mass than Maya children living in a village in Guatemala. However, they are
      shorter, on average, than children of black, Mexican-American, and white
      ethnicity living in Indiantown. Children of Maya immigrants born in the United
      States tend to be taller than immigrant children born in Guatemala or Mexico.
      Families that invest economic and social resources in their children have taller
      children. More economic successful families have taller children. Migration
      theory and political economy theory from the social sciences are combined with
      plasticity theory and life history theory (parental investment) from biology to
      interpret these data.

PMID- 9034037
TI  - Social economics of childhood glucocorticoid stress response and health.
AB  - This study examines socioeconomic conditions, psychosocial stress, and health
      among 264 infants, children, adolescents, and young adults aged 2 months to 18
      years residing in a rural Caribbean village. Fieldwork was conducted over a 9
      year period (1988-1996). Research methods and techniques include salivary
      cortisol radioimmunoassay (N = 22,438), systematic behavioral observations,
      psychological questionnaires, health evaluations, medical records, informal
      interviews, and participant observation. Analyses of data indicate complex
      relations among socioeconomic conditions, stress, and health. Household income,
      land ownership, parental education, and other socioeconomic measures are weakly
      associated with child illness. There is no evidence that apparent material
      benefits of high socioeconomic status--such as improved housing, diet, work
      loads, and access to private healthcare--have important direct effects on child
      health in this population. However, social relationships, especially family
      environment, may have important effects on childhood psychosocial stress and
      illness. Abnormal glucocorticoid response profiles, diminished immunity, and
      frequent illness are associated with unstable mating relationships for
      parents/caretakers and household composition. We suggest that family
      relationships and concomitant stress and immunosuppression are important
      intermediary links between socioeconomic conditions and child health.

PMID- 9034038
TI  - Social status, social context, and arterial blood pressure.
AB  - As social change and economic development have proceeded, the prevalence of
      chronic diseases, especially cardiovascular diseases, has increased in the
      developing world. In part this is due to the adoption of diets and other health
      behaviors characteristics of industrialized nations; in part it is a function of
      changing social and economic circumstances. In this paper, we describe the
      development and testing of a model designed to account for social and economic
      effects on cardiovascular disease risk. The model incorporates the fact that
      global economic processes have made a lifestyle characterized by the consumption
      of Euroamerican material goods and information a basis for the assignment of
      social status in local communities. But economic change at the local level is
      rarely sufficient to provide a foundation for individuals' status aspirations.
      Hence, many individuals attempt to maintain lifestyle inconsistent with their
      economic standing, a variable we term lifestyle incongruity. Here we described
      how this factor is associated with higher blood pressure in a variety of settings
      and also how the effects of lifestyle incongruity can be modified in local
      contexts by social class and social role processes. This latter process,
      contextual modification, is illustrated by data from American Samoa. In this
      example, the association of lifestyle incongruity with blood pressure is examined
      in 30 male household heads and 26 spouses. After an examination of Samoan
      ethnography focused attention on the importance of age and gender differences as
      defining social contexts of intracultural variation, the model was modified to
      assess interactions between age and gender as they affect the association of
      lifestyle incongruity and blood pressure. Lifestyle incongruity is strongly
      associated with higher systolic and diastolic blood pressure for the younger
      household heads, minimally associated with blood pressure for older household
      heads, and only slightly associated with blood pressure of their spouses. The
      regression coefficients for the lifestyle incongruity by age by sex interaction
      term was significant at P < or = 0.01 for both systolic and diastolic blood
      pressure. The consistency of these results with expectations based on the
      ethnographic record is emphasized in the interpretation. We feel that the
      lifestyle incongruity model represents and empirically successful attempt to link
      global political-economic processes, local social structure, and biological
      outcomes.

PMID- 9034039
TI  - Culture as a stressor: a revised model of biocultural interaction.
AB  - Contemporary urban societies display in high relief the action of social
      stratification on human biology. Recent studies of biological responses to urban
      environments and of socioeconomically disadvantaged people indicate that culture
      allocates risks disproportionately to some individuals and groups within society
      through its constituent values and related patterns of behavior. Although risk
      allocation is present in all societies, it is very clear in urban environments
      within stratified societies where high exposure to harmful materials is many
      times more likely for some segments of society. In urban environments, culture
      may be seen as adding stressors to the environment by concentrating naturally
      occurring materials to levels that are toxic to humans and through the creation
      of new toxic materials. In stratified societies the risk of exposure to these new
      stressors is focused on the socioeconomically disadvantaged. This exposure has
      consequences that increase the likelihood of more exposure and more socioeconomic
      disadvantage, thereby increasing social stratification. This suggests that models
      of biocultural interaction include a feedback relationship in which biological
      factors influence the sociocultural system in addition to the usual action of the
      sociocultural system on biological features and responses. This model strongly
      reinforces the view that stressors can originate from cultural arrangements.

PMID- 9034040
TI  - Origin of Amerindian Y-chromosomes as inferred by the analysis of six polymorphic
      markers.
AB  - We analysed the frequency of six Y-specific polymorphisms in 105 Amerindian males
      from seven different populations, 42 Caucasian males, and a small number of males
      of African, Chinese, and Melanesian origin. The combination of three of the six
      polymorphisms studied produced four different Y-haplogroups. The haplogroups A
      (non-variant) was the most frequent one. Eighty-five percent of Amerindians
      showing haplogroup A have the alphoid II (alpha hII) and the DYS19A Y-specific
      markers, an association that is found only in 10% of Caucasians and that has not
      been detected in Asiatics and Africans. Haplogroups C (YAP+) and D (YAP+ plus an
      A-->G transmission in the locus DYS271) are of African origin. Four percent of
      Amerindians and approximately 12% of Caucasians showed haplogroup C;
      approximately 1% of Amerindians and approximately 2% of Caucasians had haplogroup
      D. Haplogroup B is characterized by a C-->T transition in nucleotide position 373
      of the SRY gene domain; this haplogroup is found in Caucasians (approximately
      12%) and Amerindians (approximately 4%). None of the Amerindians exhibiting the
      haplogroups B, C, or D show the haplotype alpha hII/DYS19A. By haplotyping the
      the Alu insert and the DNA region surrounding the insert in YAP+ individuals, we
      could demonstrate that Amerindian Y chromosomes bearing African markers
      (haplogroups C and D) are due to recent genetic admixture. Most non-alpha
      hII/DYS19A Amerindian Y-chromosomes in haplogroup A and most cases in haplogroup
      B are also due to gene flow. We show that haplotype alpha hII/DYS19A is in
      linkage disequilibrium with a C-->T transition in the locus DYS19A. Our results
      suggest that most Amerindian Y-chromosomes derive from a single paternal lineage
      characterized by the alpha hII/DYS19A/DYS199T Amerindian-specific haplotype. The
      analysis of a larger sample of native American Y-chromosome will be required in
      order to confirm or correct this hypothesis.

PMID- 9034041
TI  - Precision grips, hand morphology, and tools.
AB  - This study asks whether there are discernable links between precision gripping,
      tool behaviors, and hand morphology in modern hominoids, which may guide
      functional interpretation of early hominid hand morphology. Findings from a three
      pronged investigation answer this question in the affirmative, as follows: (1)
      Experimental manufacture of early prehistoric tools provides evidence of
      connections between distinctive human precision grips and effective tool making.
      (A connection is not found between the "fine" thumb/index finger pad precision
      grip and early tool making.) (2) Manipulative behavior studies of chimpanzees,
      hamadryas baboons, and human show that human precision grips are distinguished by
      the greater force with which objects may be secured by the thumb and fingers of
      one hand (precision pinching) and the ability to adjust the orientation of
      gripped objects through movements at joints distal to the wrist (precision
      handling). (3) Morphological studies reveal eight featured distinctive of modern
      humans which facilitate use of these grips. Among these features are
      substantially larger moment arms for intrinsic muscles that stabilize the
      proximal thumb joints. Examination of evidence for these reveals that three of
      the eight features occur in Australopithecus afarensis, but limited thumb
      mobility would have compromised tool making. Also, Olduvai hand morphology
      strongly suggests a capacity for stone tool making. However, functional and
      behavioral implications of Sterkfontein and Swartkrans hand morphology are less
      clear. At present, no single skeletal feature can be safely relied upon as an
      indicator of distinctively human capabilities for precision gripping or tool
      making in fossil hominids.

PMID- 9034042
TI  - Endocranial hyperostosis in Sangiran 2, Gibraltar 1, and Shanidar 5.
AB  - Sangiran hominid 2 (S-2), Gibraltar hominid 1 (G-1), and Shanidar hominid 5 (SH
      5) exhibit previously undescribed bilateral, paramedian hyperostosis of the
      endocranial frontal squama that spares the frontal crest, sagittal sinus, and
      ectocranial surface. The hyperostosis is localized to the frontal (usually the
      middle third) and parietal and is consistent with a diagnosis of hyperostosis
      calvaria interna (HCI), inclusive of hyperostosis frontalis interna. The
      hyperostosis in these specimens is compared to fossil hominids from Indonesia and
      Europe and to modern human cases of HCI. The three cases of HCI reported here
      documented the existence and frequency of HCI in fossil hominids and push the
      antiquity of the disease back to nearly 1.5 million years. The relatively great
      incidence of HCI in fossil hominids adds another confounding factor to the
      problematical issue of the taxonomic significance of cranial vault thickness.

PMID- 9034043
TI  - Twenty-five thousand-year-old triple burial from Dolni Vestonice: an ice-age
      family?
AB  - In 1986 a paleolithic triple burial was discovered near Dolni Vestonice (Czech
      Republic). The occurrence of anatomic variants in all three skeletons gave rise
      to speculations that the buried individuals may have been closely related. To
      test this hypothesis the skeletons were submitted to a systematic kinship
      analysis based on odontologic and other non-metric traits. Statistical tests
      showed that the coincident occurrence of several rare traits in the individuals
      is highly unlikely to occur at random. This and further data included in the
      analysis therefore suggest that the three individuals buried together were
      genetically related and actually belonged to one family.

PMID- 9034044
TI  - Dental asymmetry, maternal obesity, and smoking.
AB  - This study examines the levels of fluctuating dental asymmetry in four samples of
      school children: those whose mothers were obese and had smoked during the
      pregnancy concerned (n = 111); those whose mothers were obese non-smokers (n =
      114); those whose mothers were non-obese smokers (n = 104); and those whose
      mothers were lean non-smokers (n = 111). The degree of fluctuating asymmetry was
      assessed by means of a rescaled asymmetry measure. Obesity was defined as
      Quetelet's index in excess of 30, and smoking status as at least 20 cigarettes
      per day during the pregnancy concerned. When the magnitudes of fluctuating
      asymmetry in children of lean smokers were compared to the control group of lean
      non-smokers, no significant univariate differences were found. Children of obese
      mothers, whether these smoked or not, were found to have significantly raised
      levels of asymmetry. An analysis of variance confirmed that the combination of
      obesity and maternal smoking was a significant predictor of fluctuating dental
      asymmetry. The teeth involved tended to be the maxillary first incisor and
      molars. It is concluded that maternal obesity has a destabilizing effect on the
      developing fetus and that this effect appears to be enhanced in obese mothers who
      smoked. This effect was absent in lean mothers, irrespective of their smoking
      status.

PMID- 9034046
TI  - EndoScope: world literature reviews

PMID- 9034045
TI  - Brief communication: first evidence of LSAMAT in non-native Americans: historic
      Senegalese from west Africa.
AB  - To date, the distinctive dental wear pattern known as LSAMAT, or "lingual surface
      attrition of the maxillary anterior teeth," has been documented in prehistoric
      samples from Brazil, Panama, and Puerto Rico only. However, new data from a
      historic Senegalese sample reveals the first example of this wear pattern outside
      the Americas. The Senegal LSAMAT is present in 45% of 22 adult crania, and is
      associated with a caries rate of 40% in 38 adults (6.7% of 534 permanent teeth).
      A correlation between LSAMAT and caries was also observed in the Latin American
      samples. In these cases, it was hypothesized that LSAMAT was caused by the
      specialized consumption of an abrasive, high carbohydrate food, such as manioc.
      Manioc is a common cultigen in Senegal; thus, it may have also caused the African
      LSAMAT. The chewing of sugar cane could have been an additional, contributing
      factor.

PMID- 9034126
TI  - Replicative senescence and cell immortality: the role of telomeres and
      telomerase.
AB  - Telomere shortening is correlated with cell senescence in vitro and cell aging in
      vivo. The telomere hypothesis suggests that telomere length serves as a mitotic
      clock for timing cellular replicative life span. Expression of telomerase
      stabilizes telomere length and allows for continual replication, or cell
      immortality. This article reviews recent evidences for the role of telomere
      length and telomerase in the regulation of cellular replicative life span. The
      therapeutic potential of manipulating telomerase expression and telomere length
      is also discussed.

PMID- 9034127
TI  - Superoxide dismutase and pulmonary oxygen toxicity.
AB  - The production of superoxide (O2-) under hyperoxic conditions is markedly
      accentuated leading to the generation of potent oxidants such as hydrogen
      peroxide (H2O2), hydroxyl radical (HO.), and peroxynitrite (ONOO-). Superoxide
      dismutase (SOD), by rapidly removing O2-, reduces the tissue concentration of O2-
      and prevents the production of HO. and ONOO-. Three forms of SOD exist in the
      lung: CuZnSOD, MnSOD, and extracellular SOD. Considerable supportive, though not
      all conclusive, evidence suggests that all three forms of SOD are essential for
      the pulmonary defense against oxygen toxicity, and that enhancement of pulmonary
      SOD has the potential of protecting against oxygen toxicity.

PMID- 9034128
TI  - Activins and activin receptors in cell growth.
AB  - Activin and inhibin, members of transforming growth factor-beta (TGFbeta)
      superfamily, have diverse and widespread effects within living organisms at many
      stages during growth and development. From the initial isolation of these growth
      factors based on their effects of FSH secretion, the study of these factors, as
      well as of the activin-binding protein follistatin, has progressed from the
      localization of the expression of the inhibin alpha subunit, activin betaA and
      betaB subunits, and activin receptors in the tissues of various organisms to the
      examination of activin and inhibin as autocrine and paracrine agents in cell
      proliferation and differentiation. The inhibitory effects on cell growth and
      differentiation that have been observed upon treatment of cells with activin
      suggest that further understanding of the bioactivity of this molecule and its
      characterization on a molecular level may aid in a more complete understanding of
      cell growth and differentiation. This minireview discusses the roles of activin,
      inhibin, and follistatin in the arenas of cell proliferation, differentiation,
      and embryogenesis, as well as the roles of these molecules in cancerous cells.

PMID- 9034129
TI  - The regulation of expression of integrin receptors.
AB  - The integrins are a family of cell surface receptors that mediate cell
      extracellular matrix and cell-cell interactions. The quantities and activities of
      these receptors are modulated during a wide variety of biological processes. A
      variety of agents have been found to affect expression of integrins and their
      function. These include cytokines, hormones, and pharmacologic agents. Mechanisms
      regulating integrin expression and function include regulation of protein levels
      by transcriptional or posttranscriptional mechanisms, alteration of protein
      structure by alternative splicing of mRNA, mobilization to the cell surface of
      preexisting intracellular stores of integrins, and modulation of receptor
      activity (inside-out signaling). We review studies that assess the effects of
      external agents on integrin levels using the cytokine TGFbeta as an example. We
      also review studies that analyze integrin regulation with an emphasis on the
      control of integrin gene transcription. This review shows that the strategies for
      integrin modulation are quite complex. This regulatory sophistication is likely
      necessary, given the critical role that integrins play in the myriad social
      interactions of cells.

PMID- 9034130
TI  - Zonal changes in proliferation in the rhesus endometrium during the late
      secretory phase and menses.
AB  - The objective of the present study was to examine the zonal changes in
      endometrial proliferation that occur during the late secretory phase, menses, and
      postmenstrual endometrial regeneration. We used as our model ovariectomized
      rhesus monkey in which artificial menstrual cycles were simulated. Our marker of
      proliferation was the immunohistochemical detection of the Ki-67 antigen. On Day
      26, as progesterone (P) levels are falling in the late secretory phase,
      proliferation in zone IV of the basalis decreased compared with Day 23 (peak P
      level). Proliferation in the upper regions of the endometrium remained
      suppressed. Three days after a single bolus injection of the potent antiprogestin
      RU-486 on Day 20, proliferation in zone IV was virtually absent compared with Day
      23 of an artificial cycle. No distinct changes in the pattern of proliferation
      were observed in the upper regions of the endometrium. On Day 1 of menses (P
      levels undetectable, estradiol [E] levels of 70-100 pg/ml), there was little
      proliferation throughout the endometrium. On Day 3 or menses, proliferation
      returned to zones II-III of the basalis and the functionalis. This proliferation
      was primarily observed in the glandular epithelia whereas little or no
      proliferation was observed in zone IV of the basalis. By Day 5 proliferation
      continued in the glandular epithelia of zones I, II, and III, and was now clearly
      observable in the stromal cells. Only minimal proliferation was observed in
      glandular epithelia of zone IV. In the absence of basal E stimulation the return
      of proliferation to the glandular epithelia in zones I, II, and III was
      dramatically reduced. These data demonstrate a reciprocal pattern of
      proliferation in glandular epithelia that is dependent on the prevailing hormonal
      stimulation. Under P dominance, proliferation is inhibited in zones I, II, and
      III, and maintained in zone IV, whereas under E dominance (Day 3 or 5)
      proliferation is driven by E stimulation in zones I, II, and III with little or
      no proliferation present in zone IV. In addition, the inhibition of proliferation
      in zone IV by the antiprogestin RU-486 and the decline of zone IV proliferation
      associated with falling P levels provide further evidence that proliferation of
      glandular epithelia in zone IV is mediated in part by P.

PMID- 9034131
TI  - Sertoli cells in culture release a pregnancy specific beta1 glycoprotein-like
      substance.
AB  - The possibility that pregnancy-specific beta1 glycoprotein (PSG) is released by
      Sertoli cells was investigated by using reverse hemolytic plaque assays which
      enable the visualization of release from individual cells in culture. We found
      that the proportions of cells releasing PSG increased gradually in 3-day old
      cultures prepared from animals of increasing age (10-, 20-, and 40-day old
      animals). The gradual appearance of PSG-releasing cells during this period
      differed markedly from that of transferrin (TF)-releasing cells, suggesting that
      the age-related development of PSG-releasing cells is regulated in a specific
      manner. PSG cells were also found in Sertoli cell cultures prepared from stage
      associated seminiferous tubule segments of adult rat testes. The percentages of
      PSG plaque-forming cells differed from one stage-associated culture to another
      with maximal proportions associated with stages III-V and XIII, and minimal
      proportions found in stages VII, and IX-XI. The abundance of Sertoli cells that
      released PSG from stage to stage differed markedly from those that released TF
      indicating that modulatory processes specific for PSG are also present in the
      adult testis. Finally, PSG cells were also identified immunocytochemically in
      cultures prepared from staged tubule segments. The proportion of PSG staining
      cells from stage to stage were found to be virtually indistinguishable from those
      identified with plaque assays. When taken together, these results show clearly
      that Sertoli cells in culture release a PSG-like molecule. Moreover, this release
      appears to be controlled in an age-related and stage-dependent manner, suggesting
      that Sertoli cells may be central to PSG function in the testis.

PMID- 9034132
TI  - Prolactin-like biological activity in the pituitary glands of the marsupial
      Monodelphis domestica and of the amphibian Rana pipiens detected by a
      colorimetric Nb2 lymphoma cell proliferation assay.
AB  - An inexpensive and reliable colorimetric microplate version of the Nb2 lymphoma
      cell proliferation bioassay for prolactin (PRL) was developed and optimized. The
      useful range of the assay is between 0.1 and 12.8 ng/ml in terms of rat pituitary
      PRL. The assay can accommodate up to 20 microl sample/well. The physiological
      relevance of the assay was verified by measuring thyrotropin-releasing hormone
      (TRH)-induced secretion of PRL in pituitary cultures and in serum samples of
      neonatal rats. Through the use of the colorimetric Nb2 assay, PRL-like
      bioactivities were demonstrated in pituitary extracts of the marsupial,
      Monodelphis domestica (1.47 ng PRL/microg protein) and of the amphibian, Rana
      pipiens (1.86 ng PRL/microg protein). Marsupial and amphibian PRLs are predicted
      to have low specific activities in the Nb2 assay. Since the PRL values were
      calculated in terms of a rat PRL standard, they probably underestimate the
      amounts of PRL present. Parallel dose-response curves were obtained with these
      pituitary extracts and standard rat PRL over a wide range of dilutions. The Nb2
      bioassay may serve as a tool for the purification of PRL from these species. The
      colorimetric version of the Nb2 bioassay may be a useful alternative to
      traditional Nb2 assays that rely on direct cell count or [3H]thymidine uptake.

PMID- 9034133
TI  - Effects of blood pH and blood lactate on growth hormone, prolactin, and
      gonadotropin release after acute exercise in male volunteers.
AB  - It has recently been found that prevention of the acidosis of anaerobic exercise
      blocks beta-endorphin release. Because heavy exercise affects secretion of other
      anterior pituitary hormones, we studied the results of alkali infusion and
      ingestion upon blood levels of four hormones: luteinizing hormone (LH), follicle
      stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). Eight male
      subjects were studied after either 2 mEq/kg placebo (NaCl) or alkali (NaHCO3)
      administered before and during exercise to exhaustion. Blood samples were
      obtained before exercise and then 15, 30, 60, 90, 120, and 180 min postexercise.
      GH and PRL but not FSH or LH increased significantly postexercise, with a peak at
      60 min, and subsequently declined back to baseline by 180 min. Base treatment
      reduced GH at baseline and postexercise (except at 60 min) and increased PRL
      significantly, particularly at 60 min. While the precise mechanisms on how
      acid/base changes affect hormone release remain to be defined, there are possible
      consequences on gonadal function and substrate availability during exercise.

PMID- 9034134
TI  - Prolactin's effects on lipoprotein lipase (LPL) activity and on LPL mRNA levels
      in cultured mouse mammary gland explants.
AB  - The in vitro effects of prolactin (PRL) on lipoprotein lipase (LPL) activity and
      on LPL mRNA levels were studied in cultured mammary tissues derived from mid
      pregnant mice. Mouse mammary gland tissues were initially incubated for 24 hr in
      M199 media containing 1 microg/ml insulin and 10(-7) M cortisol. A subsequent
      treatment of the tissues with 1 microg/ml PRL caused a 76% increase in heparin
      releasable LPL (hrLPL) activity after 24 hr. A significant increase in LPL
      activity was detected 16 hr after PRL addition, but not at earlier times. PRL at
      100 ng/ml elicited a maximum stimulation of LPL activity. When Northern
      hybridization techniques were employed, PRL was also found to increase the tissue
      content of LPL mRNA; this effect was initially detected after a 6-hr PRL
      treatment employing PRL concentrations of 50 ng/ml and above. Specificity studies
      revealed that only lactogenic hormones stimulated LPL activity and LPL mRNA
      accumulation in cultured mammary tissues. PRL also expressed a small (25%
      increase), but significant, effect on ATP citrate-lyase activity in mammary
      tissues cultured for more than 6 hr with the hormone.

PMID- 9034135
TI  - Events that stimulate release of thromboxane B2 in passive heymann nephritis.
AB  - The cause of proteinuria in passive Heymann nephritis has been attributed to the
      activation of the C5b-9 membrane attack complex following the antibody binding on
      the glomerular epithelial cell. Previous studies have shown an association
      between release of prostaglandin thromboxane B2 (TxB2) and proteinuria. Whether
      this release is dependent on antibody binding per se, or on secondary actions
      subsequent to antibody binding has not been clarified. The present study was
      designed to address this issue. Antibody binding event was experimentally
      separated from the proteinuria by employing a rabbit antibody which produces
      equivalent glomerular binding equal to that produced by a sheep antibody but
      without causing proteinuria. Comparisons were made with animals injected with the
      sheep antibody which produces all the hallmarks of the disease, including
      proteinuria. Animals injected with the rabbit antibody showed glomerular
      immunofluorescent deposits which were identical to the deposits produced by the
      control sheep antibody. However, rabbit antibody failed to produce the typical
      electron-dense subepithelial deposits, complement binding and proteinuria.
      Comparison of prostaglandin profile in isolated glomeruli revealed that TxB2 was
      unchanged in rabbit antibody-injected glomeruli (compared with its nonimmune
      antibody control). On the other hand, glomeruli from sheep antibody-injected
      animals released 45% higher TxB2 compared with their respective nonimmune
      antibody control. These data suggest that the binding of antibody per se may not
      be a sufficient stimulus for TxB2 release. Subsequent events of subepithelial
      electron dense deposit formation, complement activation, and proteinuria are
      associated with TxB2 release.

PMID- 9034136
TI  - The effects of cocaine injections on mouse thymocyte population.
AB  - C57 BL mice were injected daily with either saline or varied doses of cocaine (5
      50 mg/kg), and thymocyte subpopulations were analyzed 4 hr after the fifth
      injection. Mice injected with either 25 or 50 mg/kg of cocaine showed a decrease
      in the percentage of CD4+8+ cells and increase of CD4-8-, CD4+, and CD8+ cells.
      The absolute numbers of each subpopulation, calculated by multiplying the
      percentage of each subpopulation with the total cell number, revealed an
      extensive decline in CD4+8+, a decrease in CD8+, an increase in CD4-8-, and no
      change in the CD4+ subpopulation. Flow cytometric analysis of thymocytes and
      electrophoresis of the thymocyte DNA revealed a dosage-dependent increase in
      cells undergoing programed cell death with apoptosis. Culturing of thymocytes
      from control or drug-treated mice demonstrated an inverse relationship between
      cell viability and cocaine concentrations, suggesting that in vivo cocaine, or
      its biological products, may damage thymocytes. Incubation of normal cells with
      cocaine showed a dose-dependent decrease of viability with identical patterns of
      the alteration of cell subpopulations observed in vivo. A dose-dependent increase
      of apoptosis was also observed. In summary, we demonstrate a selective in vivo
      cocaine-induced alteration of the thymocyte subpopulations and identified
      programed cell death with apoptosis as the likely mechanism mediating this thymic
      atrophy. The comparable findings observed in vivo and in vitro support the
      concept that cocaine may directly affect some features of thymocyte biology, and
      suggest the usefulness of the in vitro system in studying cocaine effects on
      thymocyte biology.

PMID- 9034137
TI  - Quantification of changes in transforming growth factor-beta1 gene expression in
      experimental crescentic glomerulonephritis.
AB  - Transforming growth factor-beta1 (TGFbeta1) has recently been identified as a
      promoter of glomerular scarring in glomerulonephritis. The present studies
      employed polymerase chain reaction (PCR)-based methods to quantify changes in
      transcriptional activation of TGFbeta1 in experimental crescentic
      glomerulonephritis. The disease was induced in the rat, and total RNA was
      isolated from glomeruli at stages in which proliferation, crescent formation, and
      scarring were prominent features. Total glomerular RNA was reverse transcribed
      (RT) to cDNA, and RT products were subsequently analyzed by comparative and
      competitive PCR. Enhanced TGFbeta1 expression was apparent at the onset of
      proliferative glomerulonephritis and prominent during the phase of crescent
      formation. The observations indicate that PCR-based methods allow quantitation of
      changes in glomerular TGFbeta1 expression in the course of glomerulonephritis.

PMID- 9034139
TI  - Suppression of apoptosis by nitric oxide via inhibition of interleukin-1beta
      converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like
      proteases.
AB  - Physiological levels of shear stress alter the genetic program of cultured
      endothelial cells and are associated with reduced cellular turnover rates and
      formation of atherosclerotic lesions in vivo. To test the hypothesis that shear
      stress (15 dynes/cm2) interferes with programmed cell death, apoptosis was
      induced in human umbilical venous cells (HUVEC) by tumor necrosis factor-alpha
      (TNF-alpha). Apoptosis was quantified by ELISA specific for histone-associated
      DNA-fragments and confirmed by demonstrating the specific pattern of
      internucleosomal DNA-fragmentation. TNF-alpha (300 U/ml) mediated increase of DNA
      fragmentation was completely abrogated by shear stress (446 +/- 121% versus 57 +/
      11%, P <0.05). This anti-apoptotic activity of shear stress decreased after
      pharmacological inhibition of endogenous nitric oxide (NO)-synthase by NG
      monomethyl-L-arginine and was completely reproduced by exogenous NO-donors. The
      activation of interleukin-1beta-converting enzyme (ICE)-like and cysteine
      protease protein (CPP)-32-like cysteine proteases was required to mediate TNF
      alpha-induced apoptosis of HUVEC. Endothelial-derived nitric oxide (NO) as well
      as exogenous NO donors inhibited TNF-alpha-induced cysteine protease activation.
      Inhibition of CPP-32 enzyme activity was due to specific S-nitrosylation of Cys
      163, a functionally essential amino acid conserved among ICE/CPP-32-like
      proteases. Thus, we propose that shear stress-mediated NO formation interferes
      with cell death signal transduction and may contribute to endothelial cell
      integrity by inhibition of apoptosis.

PMID- 9034138
TI  - Induction of apoptosis and T helper 2 (Th2) responses correlates with peptide
      affinity for the major histocompatibility complex in self-reactive T cell
      receptor transgenic mice.
AB  - Multiple sclerosis is an autoimmune disease thought to be mediated by CD4+ T
      helper cells (Th). Experimental autoimmune encephalomyelitis is a rodent model of
      multiple sclerosis and has been used extensively to explore a variety of
      immunotherapies using soluble protein or peptide antigens. The underlying
      mechanisms of such therapy have been attributed to induction of T cell anergy, a
      switch in Th1 to Th2 responses, or peripheral deletion of autoreactive T cells.
      In this study, we have developed transgenic mice expressing a T cell receptor
      (TCR) specific for the NH2-terminal peptide Ac1-11 of the autoantigen myelin
      basic protein to explore the mechanism of soluble peptide therapy. T cells from
      these mice are highly skewed toward the CD4 population and have an abnormal
      thymic architecture, a phenomenon found in other TCR transgenic mice that exhibit
      a highly skewed CD4/CD8 ratio. Soluble Ac1-11 or the analogues Ac 1-11 [4A] or
      Ac1-11[4Y] (which bind to the major histocompatibility complex [MHC] class II
      molecule I-Au with increasing affinities) given intravenously activates T cells,
      rendering cells hyperresponsive in vitro for at least two days after injection.
      Concomitantly, T cells apoptose in the periphery, the degree of which correlates
      with the affinity of the peptide for the MHC. In addition, a shift in the T
      helper phenotype of the surviving T cells occurs such that the low affinity
      peptide, Ac1-11, induces primarily a Th1 response, whereas the highest affinity
      peptide, Ac1-11[4Y], induces primarily a Th2 type response. These data show that
      both the nature and the presumed number of the peptide-MHC complexes formed
      during specific peptide therapy affect both the degree of peripheral programmed
      cell death as well as the outcome of the T helper subset response in vivo,
      leading to amelioration of disease.

PMID- 9034141
TI  - Change in coreceptor use correlates with disease progression in HIV-1--infected
      individuals.
AB  - Recent studies have identified several coreceptors that are required for fusion
      and entry of Human Immunodeficiency Virus type 1 (HIV-1) into CD4+ cells. One of
      these receptors, CCR5, serves as a coreceptor for nonsyncytium inducing (NSI),
      macrophage-tropic strains of HIV-1, while another, fusin or CXCR-4, functions as
      a coreceptor for T cell line-adapted, syncytium-inducing (SI) strains. Using
      sequential primary isolates of HIV-1, we examined whether viruses using these
      coreceptors emerge in vivo and whether changes in coreceptor use are associated
      with disease progression. We found that isolates of HIV-1 from early in the
      course of infection predominantly used CCR5 for infection. However, in patients
      with disease progression, the virus expanded its coreceptor use to include CCR5,
      CCR3, CCR2b, and CXCR-4. Use of CXCR-4 as a coreceptor was only seen with primary
      viruses having an SI phenotype and was restricted by the env gene of the virus.
      The emergence of variants using this coreceptor was associated with a switch from
      NSI to SI phenotype, loss of sensitivity to chemokines, and decreasing CD4+ T
      cell counts. These results suggest that HIV-1 evolves during the course of
      infection to use an expanded range of coreceptors for infection, and that this
      adaptation is associated with progression to AIDS.

PMID- 9034140
TI  - Changes in locus-specific V(D)J recombinase activity induced by immunoglobulin
      gene products during B cell development.
AB  - The process of V(D)J recombination is crucial for regulating the development of B
      cells and for determining their eventual antigen specificity. Here we assess the
      developmental regulation of the V(D)J recombinase directly, by monitoring the
      double-stranded DNA breaks produced in the process of V(D)J recombination. This
      analysis provides a measure of recombinase activity at immunoglobulin heavy and
      light chain loci across defined developmental stages spanning the process of B
      cell development. We find that expression of a complete immunoglobulin heavy
      chain protein is accompanied by a drastic change in the targeting of V(D)J
      recombinase activity, from being predominantly active at the heavy chain locus in
      pro-B cells to being exclusively restricted to the light chain loci in pre-B
      cells. This switch in locus-specific recombinase activity results in allelic
      exclusion at the immunoglobulin heavy chain locus. Allelic exclusion is
      maintained by a different mechanism at the light chain locus. We find that
      immature, but not mature, B cells that already express a functional light chain
      protein can undergo continued light chain gene rearrangement, by replacement of
      the original rearrangement on the same allele. Finally, we find that the
      developmentally regulated targeting of V(D)J recombination is unaffected by
      enforced rapid transit through the cell cycle induced by an E mu-myc transgene.

PMID- 9034142
TI  - Effects of epitope modification on T cell receptor-ligand binding and antigen
      recognition by seven H-2Kd-restricted cytotoxic T lymphocyte clones specific for
      a photoreactive peptide derivative.
AB  - We tested for antigen recognition and T cell receptor (TCR)-ligand binding 12
      peptide derivative variants on seven H-2Kd-restricted cytotoxic T lymphocytes
      (CTL) clones specific for a bifunctional photoreactive derivative of the
      Plasmodium berghei circumsporozoite peptide 252-260 (SYIPSAEKI). The derivative
      contained iodo-4-azidosalicylic acid in place of PbCS S-252 and 4-azidobenzoic
      acid on PbCS K-259. Selective photoactivation of the N-terminal photoreactive
      group allowed crosslinking to Kd molecules and photoactivation of the orthogonal
      group to TCR. TCR photoaffinity labeling with covalent Kd-peptide derivative
      complexes allowed direct assessment of TCR-ligand binding on living CTL. In most
      cases (over 80%) cytotoxicity (chromium release) and TCR-ligand binding differed
      by less than fivefold. The exceptions included (a) partial TCR agonists (8
      cases), for which antigen recognition was five-tenfold less efficient than TCR
      ligand binding, (b) TCR antagonists (2 cases), which were not recognized and
      capable of inhibiting recognition of the wild-type conjugate, (c) heteroclitic
      agonists (2 cases), for which antigen recognition was more efficient than TCR
      ligand binding, and (d) one partial TCR agonist, which activated only Fas
      (C1)95), but not perforin/granzyme-mediated cytotoxicity. There was no
      correlation between these divergences and the avidity of TCR-ligand binding,
      indicating that other factors than binding avidity determine the nature of the
      CTL response. An unexpected and novel finding was that CD8-dependent clones
      clearly incline more to TCR antagonism than CD8-independent ones. As there was no
      correlation between CD8 dependence and the avidity of TCR-ligand binding, the
      possibility is suggested that CD8 plays a critical role in aberrant CTL function.

PMID- 9034143
TI  - Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T
      cells.
AB  - The requirements for inducing downregulation of alpha/beta T cell receptor (TCR)
      molecules on naive major histocompatibility complex class I-restricted T cells
      was investigated with 2C TCR transgenic mice and defined peptides as antigen.
      Confirming previous results, activation of 2C T cells in response to specific
      peptides required CD8 expression on the responder cells and was heavily dependent
      upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells
      (APC). These stringent requirements did not apply to TCR downregulation. Thus,
      TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not
      require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but
      only with limiting doses of peptides. TCR downregulation was most prominent with
      high affinity peptides and appeared to be neither obligatory nor sufficient for T
      cell activation. In marked contrast to T cell activation, TCR downregulation was
      resistant to various metabolic inhibitors. The biological significance of TCR
      downregulation is unclear, but could be a device for protecting T cells against
      excessive signaling.

PMID- 9034144
TI  - A transgenic marker for mouse B lymphoid precursors.
AB  - Three lines of transgenic mice have been generated which express human CD25 under
      the control of the 722-base pair region located immediately 5' of the precursor
      (pre)-B cell-specific lambda5 gene. All three strains express human CD25 in
      parallel to endogenous lambda5 on pre-B cells, but not on mature B lymphocytes or
      other blood cell lineages. High expression of human CD25 on B lineage cells of
      transgenic mice has allowed the identification of a new B220+CD19-lambda5+
      precursor of the B220+CD19+lambda5+ c-kit+ pre-BI cells. Both types of precursors
      are clonable on stromal cells in the presence of interleukin-7. The CD19-
      precursors have a sizeable part of their immunoglobulin heavy chain gene loci in
      germline configuration, while the CD19+ pre-BI cells are predominantly DJH
      rearranged. The results indicate that random integration of the 722-bp 5' region
      of the lambda5 gene into the mouse genome confers tissue and differentiation
      stage-specific expression of a transgene.

PMID- 9034145
TI  - IgE enhances mouse mast cell Fc(epsilon)RI expression in vitro and in vivo:
      evidence for a novel amplification mechanism in IgE-dependent reactions.
AB  - The binding of immunoglobulin E (IgE) to high affinity IgE receptors
      (Fc(epsilon)RI) expressed on the surface of mast cells primes these cells to
      secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory
      mediators, which includes cytokines that can also have immunoregulatory
      activities. This IgE- and antigen-specific mast cell activation and mediator
      production is thought to be critical to the pathogenesis of allergic disorders,
      such as anaphylaxis and asthma, and also contributes to host defense against
      parasites. We now report that exposure to IgE results in a striking (up to 32
      fold) upregulation of surface expression of Fc(epsilon)RI on mouse mast cells in
      vitro or in vivo. Moreover, baseline levels of Fc(epsilon)RI expression on
      peritoneal mast cells from genetically IgE-deficient (IgE -/-) mice are
      dramatically reduced (by approximately 83%) compared with those on cells from the
      corresponding normal mice. In vitro studies indicate that the IgE-dependent
      upregulation of mouse mast cell Fc(epsilon)RI expression has two components: an
      early cycloheximide-insensitive phase, followed by a later and more sustained
      component that is highly sensitive to inhibition by cycloheximide. In turn, IgE
      dependent upregulation of Fc(epsilon)RI expression significantly enhances the
      ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4
      in response to challenge with IgE and specific antigen. The demonstration that
      IgE-dependent enhancement of mast cell Fc(epsilon)RI expression permits mast
      cells to respond to antigen challenge with increased production of
      proinflammatory and immunoregulatory mediators provides new insights into both
      the pathogenesis of allergic diseases and the regulation of protective host
      responses to parasites.

PMID- 9034146
TI  - Mouse Ly-49A interrupts early signaling events in natural killer cell
      cytotoxicity and functionally associates with the SHP-1 tyrosine phosphatase.
AB  - The lytic activity of natural killer (NK) cells is inhibited by the expression of
      class I major histocompatibility complex (MHC) antigens on target cells. In
      murine NK cells, Ly-49A mediates inhibition of cytotoxicity in response to the
      class I MHC antigen H-2Dd. In this report, we studied the function of mouse Ly
      49A in both the rat NK cell tumor line, RNK-16, transfected with Ly-49A cDNA, and
      in primary NK cells. We show that ligation of Ly-49A by H-2Dd inhibits early
      signaling events during target cell stimulation, including polyphosphoinositide
      turnover and tyrosine phosphorylation. We also show that Ly-49A directly
      associates with the cytoplasmic tyrosine phosphatase SHP-1, and that Ly-49A
      function is impaired in NK cells from SHP-1 mutant viable motheaten mice and from
      SHP-1-deficient motheaten mice. Finally, we demonstrate that mutational
      substitution of the tyrosine within the proposed SHP-1 binding motif in Ly-49A
      completely abrogates inhibition of NK cell cytotoxicity through this receptor.
      These results demonstrate that Ly-49A interrupts early activating signals in NK
      cells, and that SHP-1 is an important mediator of Ly-49A function.

PMID- 9034147
TI  - Epitope location in the Cryptococcus neoformans capsule is a determinant of
      antibody efficacy.
AB  - Monoclonal antibodies (mAbs) to the polysaccharide capsule of Cryptococcus
      neoformans can prolong survival in mice. However, the properties of antibodies
      that mediate protection are not fully understood. The IgM mAbs 12A1 and 13F1
      originated from the same B cell and differ only by somatic mutations in their
      variable regions; yet mAb 12A1 protects against serotype D infection, while mAb
      13F1 does not. Phage peptide display libraries were used to analyze the fine
      specificity of these two mAbs. The selection of distinct peptide motifs from
      identical libraries confirmed that mAbs 12A1 and 13F1 bound to two distinct
      epitopes. Immunofluorescence and immunoelectron microscopy studies revealed
      differences in antibody localization within the capsule of serotype D strain; mAb
      12A1 bound to the outer rim of the capsule resulting in an annular pattern,
      whereas mAb 13F1 bound throughout the capsule and had a punctate appearance. The
      difference in the binding pattern of mAb 12A1 and 13F1 was not observed on
      serotype A organisms, where both mAbs bound to the capsule with an annular
      fluorescence pattern. The fluorescence pattern of binding correlated with
      protective efficacy; mAb 13F1 prolonged survival of mice infected with the J11
      serotype A strain (annular fluorescence), but not serotype D strains (punctate
      pattern). Annular binding, but not punctate binding, was associated with
      increased opsonic efficacy for phagocytosis of C. neoformans by J774.16
      macrophage-like cells. The correlation between capsular binding pattern, opsonic
      activity, and ability to prolong survival suggests that the efficacy of
      anticryptococcal antibodies is dependent upon where they bind in the
      polysaccharide capsule.

PMID- 9034148
TI  - The immunodominant antigen of an ultraviolet-induced regressor tumor is generated
      by a somatic point mutation in the DEAD box helicase p68.
AB  - The genetic origins of CD8+ T cell-recognized unique antigens to which mice
      respond when immunized with syngeneic tumor cells are unknown. The ultraviolet
      light-induced murine tumor 8101 expresses an H-2Kb-restricted immunodominant
      antigen, A, that induces cytolytic CD8+ T cells in vivo A+ 8101 cells are
      rejected by naive mice while A- 8101 tumor cells grow. To identify the antigen H
      2Kb molecules were immunoprecipitated from A+ 8101 cells and peptides were eluted
      by acid. The sensitizing peptide was isolated by sequential reverse-phase HPLC
      and sequenced using microcapillary HPLC-triple quadruple mass spectrometry. The
      peptide, SNFVFAGI, matched the sequence of the DEAD box protein p68 RNA helicase
      except for a single amino acid substitution, caused by a single nucleotide
      change. This mutation was somatic since fibroblasts from the mouse of tumor
      origin expressed the wild-type sequence. The amino acid substitution created an
      anchor for binding of the mutant peptide to H-2Kb. Our results are consistent
      with mutant p68 being responsible for rejection of the tumor. Several functions
      of p68, which include nucleolar assembly and inhibition of DNA unwinding, may be
      mediated through its IQ domain, which was altered by the mutation. This is the
      first description of a somatic tumor-specific mutation in the coding region of a
      nucleic acid helicase.

PMID- 9034149
TI  - The single positive T cells found in CD3-zeta/eta-/- mice overtly react with self
      major histocompatibility complex molecules upon restoration of normal surface
      density of T cell receptor-CD3 complex.
AB  - CD3-zeta/eta-deficient mice have small thymuses containing cells that show a
      profound reduction in the surface levels of T cell receptors and terminate their
      differentiation at the CD4+CD8+ stage. Rather unexpectedly, CD3- or very low
      single positive T cells accumulate over time in the spleen and lymph nodes of CD3
      zeta/eta-deficient mice after a process dependent on MHC expression. Fusion of
      these peripheral T cells with a CD3-zeta-positive derivative of the BW5147 TCR
      alpha-/beta- thymoma resulted in hybridomas that do express an heterogeneous set
      of T cell receptor alpha/beta dimers at their surface and at density comparable
      to those found in hybridomas derived from wild-type peripheral T cells. We have
      investigated the specificities of these T cell receptors using spleen cells from
      congenic and mutant mouse strains, and showed that the majority of them readily
      recognized self-MHC class I or class II molecules. These results demonstrate that
      by increasing the density and/or output of the T cell receptors expressed in
      peripheral T cells, one can confer them with the capacity to respond to normal
      density of self-MHC molecules.

PMID- 9034150
TI  - Natural resistance to infection with intracellular pathogens: the Nramp1 protein
      is recruited to the membrane of the phagosome.
AB  - The Nramp1 (natural-resistance-associated macrophage protein 1) locus (Bcg, Ity,
      Lsh) controls the innate resistance or susceptibility of mice to infection with a
      group of unrelated intracellular parasites which includes Salmonella, Leishmania,
      and Mycobacterium. Nramp1 is expressed exclusively in professional phagocytes and
      encodes an integral membrane protein that shares structural characteristics with
      ion channels and transporters. Its function and mechanism of action remain
      unknown. The intracellular localization of the Nramp1 protein was analyzed in
      control 129/sv and mutant Nramp1-/- macrophages by immunofluorescence and
      confocal microscopy and by biochemical fractionation. In colocalization studies
      with a specific anti-Nramp1 antiserum and a panel of control antibodies directed
      against known cellular structures, Nramp1 was found not to be expressed at the
      plasma membrane but rather localized to the late endocytic compartments (late
      endosome/lysosome) of resting macrophages in a Lamp1 (lysosomal-associated
      membrane protein 1)-positive compartment. Double immunofluorescence studies and
      direct purification of latex bead-containing phagosomes demonstrated that upon
      phagocytosis, Nramp1 is recruited to the membrane of the phagosome and remains
      associated with this structure during its maturation to phagolysosome. After
      phagocytosis, Nramp1 is acquired by the phagosomal membrane with time kinetics
      similar to Lamp1, but clearly distinct from those of the early endosomal marker
      Rab5. The targeting of Nramp1 from endocytic vesicles to the phagosomal membrane
      supports the hypothesis that Nramp1 controls the replication of intracellular
      parasites by altering the intravacuolar environment of the microbe-containing
      phagosome.

PMID- 9034151
TI  - Induction of the early growth response (Egr) family of transcription factors
      during thymic selection.
AB  - There is little known about the regulation of gene expression during TCR-mediated
      differentiation of immature CD4+8+ (double positive) thymocytes into mature T
      cells. Using the DPK CD4+8+ thymocyte precursor cell line, we demonstrate that
      the early growth response-1 gene (Erg-1), encoding a zinc finger transcription
      factor, is rapidly upregulated after TCR stimulation. We also report that Egr-1
      is expressed by a subset of normal double positive thymocytes in the thymic
      cortex, as well by a majority of medullary single positive thymocytes. Expression
      of Egr-1 is dramatically reduced in the thymus of major histocompatibility
      complex knockout mice, but can be induced by anti-CD3 antibody stimulation of
      isolated thymocytes from these animals. These and other data suggest that high
      level expression of Egr-1 in the thymus is a consequence of selection. A similar
      pattern of expression is found for family members Egr-2 and Egr-3. Using the DPK
      cell line, we also demonstrate that expression of Egr-1, 2, and 3 is dependent
      upon ras activation, as is the initiation of differentiation to a single positive
      cell. In contrast, the calcineurin inhibitor cyclosporin A, which inhibits DPK
      cell differentiation as well as positive selection, inhibits expression of Egr-2
      and Egr-3, but not Egr-1. The identification of the Egr family in this context
      represents the first report of a link between the two known signaling pathways
      involved in positive selection and downstream transcriptional regulators.

PMID- 9034152
TI  - Mapping the active site of CD59.
AB  - CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane
      attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a
      member of the Ly6 superfamily of proteins and is important in protecting host
      cells from the lytic and proinflammatory activity of the MAC. CD59 functions by
      binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane
      insertion and polymerization. We present data obtained from a combination of
      molecular modeling and mutagenesis techniques, which together indicate that the
      active site of CD59 is located in the vicinity of a hydrophobic groove on the
      face of the molecule opposite to a "hydrophobic strip" suggested earlier. In
      addition, removal of the single N-linked glycosylation site at Asn18 of CD59
      resulted in an enhancement of complement inhibitory activity.

PMID- 9034153
TI  - Extramedullary expansion of hematopoietic progenitor cells in interleukin (IL)-6
      sIL-6R double transgenic mice.
AB  - Soluble cytokine receptors modulate the activity of their cognate ligands.
      Interleukin (IL)-6 in association with the soluble IL-6 receptor (sIL-6R) can
      activate cells expressing the gp130 signal transducer lacking the specific IL-6R.
      To investigate the function of the IL-6-sIL-6R complex in vivo and to
      discriminate the function of the IL-6-sIL-6R complex from the function of IL-6
      alone, we have established a transgenic mouse model. Double-transgenic mice
      coexpressing IL-6 and sIL-6R were generated and compared with IL-6 and sIL-6R
      single-transgenic mice. The main phenotype found in IL-6-sIL-6R mice was a
      dramatic increase of extramedullary hematopoietic progenitor cells in liver and
      spleen but not in the bone marrow. In IL-6 single-transgenic mice and sIL-6R
      single-transgenic mice no such effects were observed. The high numbers of
      hematopoietic progenitor cells were reflected by a strong increase of peripheral
      blood cell numbers. Therefore, activators of the gp130 signal transducer like the
      IL-6-IL-6R complex may represent most powerful stimulators for extramedullary
      hematopoietic progenitor cells. gp130 activators may become important for the
      expansion of hematopoietic progenitor cells in vivo and in vitro.

PMID- 9034154
TI  - CD45RC isoforms define two types of CD4 memory T cells, one of which depends on
      persisting antigen.
AB  - The cellular basis of immunological memory remains a controversial area with
      respect to the identity of memory T cells and the role of persisting antigen. CD4
      T cells are phenotypically divided by the expression of high and low molecular
      weight isoforms of CD45, surface markers that are frequently used to identify
      "naive" (CD45Rhigh) and "memory" (CD45Rlow) subsets. The latter subset responds
      rapidly in antigen recall assays but paradoxically has a short life span, a
      property that is difficult to reconcile with long-term memory. The present study
      examines these issues using a DTH (delayed-type hypersensitivity) model in which
      contact sensitivity to dinitrochlorobenzene (DNCB) was transferred to athymic
      nude rats by recirculating CD4 T cell subsets defined in the rat by the anti
      CD45RC mAb OX22. As expected, CD45RC+ (but not RC-) CD4 T cells from normal
      unprimed rats transferred a DNCB-specific DTH response, whereas, 4 d after
      sensitization the CD45RC- (memory) subset alone contained the DNCB reactivity.
      However, when donor cells were collected from thymectomized rats sensitized two
      mo earlier, DNCB-specific responses were transferred by both CD45RC- and RC+
      subsets suggesting that many of the latter had developed from cells with a memory
      phenotype. This was confirmed when CD45RC CD4 T cells from 4-d primed rats were
      parked in intermediate nude recipients and recovered 2 mo later. DNCB-specific
      activity was now found wholly within the CD45RC+ "revertant" subset; the CD45RC
      CD4 T cell population was devoid of activity. Importantly, we found that the
      total switch-back from CD45RC- to RC+ could be prevented, apparently by
      persisting antigen. The results indicate that there are two functionally distinct
      categories of memory T cells: one, a short-lived CD45Rlow type which orchestrates
      the rapid kinetics, the other, a longer-lived CD45Rhigh revertant which ensures
      that immunological memory endures.

PMID- 9034155
TI  - A novel migration pathway for rat dendritic cells from the blood: hepatic
      sinusoids-lymph translocation.
AB  - The migration pathways for dendritic cells (DC) from the blood are not yet
      completely resolved. In our previous study, a selective recruitment of DC
      progenitors from the blood to the liver was suggested. To clarify the role of the
      hepatic sinusoids in the migration of blood DC, relatively immature DC and mature
      DC were isolated from hepatic and intestinal lymph, and intravenously transferred
      to allogeneic hosts. It was then possible to detect small numbers of DC within
      secondary lymphoid tissues either by immunostaining for donor type major
      histocompatibility complex class I antigen or, at much higher sensitivity, for
      bromodeoxyuridine incorporated by proliferating cells (mainly T lymphocytes),
      which responded to the alloantigen presented by the administered DC. The
      intravenously injected DC accumulated in the paracortex of regional lymph nodes
      of the liver via a lymph-borne pathway. Intravenously injected fluorochrome
      labeled syngeneic DC behaved similarly. In contrast, very few DC were found in
      spleen sections and were hardly detectable in other lymph nodes or in other
      tissues. An in situ cell binding assay revealed a significant and selective
      binding of DC to Kupffer cells in liver cryosections. It is concluded that rat DC
      can undergo a blood-lymph translocation via the hepatic sinusoids, but not via
      the high endothelial venules of lymph nodes. Hence the hepatic sinusoids may act
      as a biological concentrator of blood DC into the regional hepatic nodes. Kupffer
      cells may play an important role in this mechanism.

PMID- 9034156
TI  - Targeted disruption of the chemokine eotaxin partially reduces antigen-induced
      tissue eosinophilia.
AB  - The chemokines are a large group of chemotactic cytokines that regulate leukocyte
      trafficking and have recently been shown to inhibit human immunodeficiency virus
      entry into cells. Eotaxin is a C-C chemokine implicated in the recruitment of
      eosinophils in a variety of inflammatory disorders and, unlike all other
      eosinophil chemoattractants, is eosinophil specific. However, given the large
      number of chemoattractants that have activities on eosinophils, it is unclear
      whether eotaxin has an important role in vivo. Furthermore, it remains unclear
      why there is constitutive expression of eotaxin in healthy states in the absence
      of eosinophilic inflammation. To begin to determine the significance of eotaxin
      at baseline and during eosinophil-mediated disease processes, we have used
      targeted gene disruption to generate mice that are deficient in eotaxin. Such
      mice demonstrate that eotaxin enhances the magnitude of the early (but not late)
      eosinophil recruitment after antigen challenge in models of asthma and stromal
      keratitis. Surprisingly, a role for eotaxin in regulating the constitutive number
      of eosinophils in the peripheral circulation is also demonstrated. These results
      indicate a contributory role for eotaxin in the generation of peripheral blood
      and antigen-induced tissue eosinophilia.

PMID- 9034157
TI  - Effects of breeding environments on generation and activation of autoreactive B-1
      cells in anti-red blood cell autoantibody transgenic mice.
AB  - In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B
      cells are deleted except for B-1 cells in the peritoneal cavity and the gut.
      About one-half of the auto Ab Tg mice suffer from autoimmune hemolytic anemia
      (AIHA) in the conventional condition. Oral administration of lipopolysaccharides
      activates B-1 cells and induces autoimmune symptoms in the Tg mice, suggesting
      that the autoimmune disease in anti-RBC autoAb Tg mice is triggered by
      infections. To examine the association of bacterial infections with the
      generation of B-1 cells and the occurrence of the autoimmune disease, we analyzed
      anti-RBC autoAb Tg mice bred in germ-free and specific pathogen-free conditions.
      In germ-free conditions, few peritoneal B-1 cells were detected, while a
      significant number of peritoneal B-1 cells existed in specific pathogen-free
      conditions. In both conditions, no mice suffered from AIHA. However, when these
      Tg mice were transferred to the conventional condition or injected with
      lipopolysaccharide, peritoneal B-1 cells expanded and some of these mice suffered
      from AIHA. These results clearly showed that bacterial infections are responsible
      for both the expansion of B-1 cells and the onset of the autoimmune disease in
      these Tg mice.

PMID- 9034158
TI  - NKG2A complexed with CD94 defines a novel inhibitory natural killer cell
      receptor.
AB  - CD94 is a C-type lectin expressed by natural killer (NK) cells and a subset of T
      cells. Blocking studies using anti-CD94 mAbs have suggested that it is a receptor
      for human leukocyte antigen class I molecules. CD94 has recently been shown to be
      a 26-kD protein covalently associated with an unidentified 43-kD protein(s). This
      report shows that NKG2A, a 43-kD protein, is covalently associated with CD94 on
      the surface of NK cells. Cell surface expression of NKG2A is dependent on the
      association with CD94 as glycosylation patterns characteristic of mature proteins
      are found only in NKG2A that is associated with CD94. Analysis of NK cell clones
      showed that NKG2A was expressed in all NK cell clones whose CD16-dependent
      killing was inhibited by cross-linking CD94. The induction of an inhibitory
      signal is consistent with the presence of two immunoreceptor tyrosine-based
      inhibitory motifs (V/LXYXXL) on the cytoplasmic domain of NKG2A. Similar motifs
      are found on Ly49 and killer cell inhibitory receptors, which also transmit
      negative signals to NK cells.

PMID- 9034159
TI  - Sulfation and sulfotransferases. Introduction: changing view of sulfation and the
      cytosolic sulfotransferases.

PMID- 9034160
TI  - Sulfation and sulfotransferases 1: Sulfotransferase molecular biology: cDNAs and
      genes.
AB  - Sulfotransferase (ST) enzymes catalyze the sulfate conjugation of many hormones,
      neurotransmitters, drugs, and xenobiotic compounds. These reactions result in
      enhanced renal excretion of the sulfate-conjugated reaction products, but they
      can also lead to the formation of "bioactivated" metabolites. ST enzymes are
      members of an emerging gene superfamily that presently includes phenol ST (PST),
      hydroxysteroid ST (HSST), and, in plants, flavonol ST (FST) "families," members
      of which share at least 45% amino acid sequence identity. These families can be
      further subdivided into "subfamilies" that are at least 60% identical in amino
      acid sequence. For example, the PST family includes both PST and estrogen ST
      (EST) subfamilies. Amino acid sequence motifs exist within ST enzymes that are
      conserved throughout phylogeny. These signature sequences may be involved in the
      binding of 3'-phosphoadenosine-5 '-phosphosulfate, the cosubstrate for the
      sulfonation reaction. There are presently five known human cytosolic ST enzymes:
      an EST, an HSST, and three PSTs. cDNAs and genes for all of these enzymes have
      been cloned, and chromosomal localizations have been reported for all five genes.
      Genes for these human enzymes, as well as those of other mammalian cytosolic ST
      enzymes that have been cloned, show a high degree of structural homology, with
      conservation of the locations of most intron/exon splice junctions. Human ST
      enzyme expression varies among individuals. Functionally significant genetic
      polymorphisms for ST enzymes in humans have been reported, and other molecular
      genetic mechanisms that might be involved in the regulation of the expression of
      these enzymes are being explored. Knowledge of the molecular biology of cytosolic
      ST enzymes, when placed within a context provided by decades of biochemical
      research, promises to significantly enhance our understanding of the regulation
      of the sulfate conjugation of hormones, neurotransmitters, and drugs.

PMID- 9034161
TI  - Hepatic canalicular membrane. Introduction: transport across the hepatocyte
      canalicular membrane.

PMID- 9034162
TI  - Hepatic canalicular membrane 1: The role of mdr2 P-glycoprotein in hepatobiliary
      lipid transport.
AB  - The small apical (canalicular) domains of hepatocytes form a luminal meshwork of
      tubules between adjacent hepatocytes and are the sites of primary bile formation.
      Organic compounds are transported across this membrane domain against high
      concentration gradients. It has been recognized in recent years that the
      hepatocyte is harnessed with a set of canalicular ATP-dependent transport
      proteins, specialized in this uphill transport. Bile salts, organic anions,
      cations, and neutral amphipaths are all pumped into the bile via such primary
      active transporters. Functionally, these transporters resemble ABC transporters
      overexpressed in cells with the multidrug resistance phenotype. Indeed, those
      transporters that have been characterized at the molecular level turn out to be
      new, or already recognized, members of this family. Phospholipid secretion across
      the canalicular membrane of the mouse is also mediated by a member of this
      family, mdr2 P-glycoprotein. This was demonstrated by the absence of phospholipid
      secretion into bile of mice with a disrupted mdr2 gene and by subsequent
      demonstration of phospholipid translocation in cells that overexpress this
      protein. The recognition of mdr2 P-glycoprotein as a phospholipid flippase sheds
      new light on the function of P-glycoproteins and is an important step in
      understanding the mechanism of biliary lipid secretion.

PMID- 9034163
TI  - Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of
      alternative promoter usage.
AB  - Family 19 of the P450 super family is responsible for the conversion of C19
      androgenic steroids to the corresponding estrogens, a reaction known as
      aromatization because it involves conversion of the delta4-3-one A-ring of the
      androgens to the corresponding phenolic A-ring characteristic of estrogens. The
      gene encoding human aromatase has been cloned and characterized and shown to be
      unusual compared to genes encoding other P450 enzymes, because there are numerous
      untranslated first exons that occur in aromatase transcripts in a tissue-specific
      fashion due to differential splicing as a consequence of the use of tissue
      specific promoters. Thus, expression in the ovary uses a proximal promoter that
      is regulated primarily by cAMP. On the other hand, expression in the placenta
      uses a distal promoter located at least 40 kb upstream of the start of
      transcription that is regulated by retinoids. Other promoters are used in brain
      and adipose tissue. In the latter case, class I cytokines such as IL-6 and IL-11,
      as well as TNF-alpha, are important regulatory factors. A common 3'-splice
      junction located upstream of the start of translation is used in all of the
      splicing events involved in the use of these various promoters. Thus, the coding
      region of the transcripts, and hence the protein, are identical regardless of the
      tissue site of expression; what differs in a tissue-specific fashion is the 5'
      end of the transcripts. This pattern of expression has great significance both
      from a phylogenetic and ontogenetic standpoint, as well as for the physiology and
      pathophysiology of estrogen formation, as will be discussed in this review.

PMID- 9034164
TI  - The role of serine/threonine phosphorylation in hematopoietic cytokine receptor
      signal transduction.
AB  - The hematopoietic cytokine receptors rapidly activate tyrosine phosphorylation
      after ligand engagement. In addition, however, serine/threonine phosphorylation
      of important effector molecules also icreases. Interleukins 2-5 and granulocyte
      macrophage colony stimulating factor all activate protein kinase C. This results
      in serine/threonine phosphorylation of such important regulatory molecules as Raf
      1 kinase, myristoylated alanine-rich C kinase substrate, and SOS. These
      phosphorylated effector molecules are regulators of important genes related to
      cell survival and proliferation. In addition, as yet uncharacterized
      serine/threonine kinases associate directly with the hematopoietic receptor
      subunits themselves. These kinases may contribute to the phosphorylation of the
      STAT family of transcription factors that is important in regulating cytokine
      specific gene inductions. Thus, it is time to begin integrating serine/threonine
      kinases into the postulated signaling pathways activated by hematopoietic
      cytokine receptors.

PMID- 9034165
TI  - Lipid biochemistry: functions of glycerolipids and sphingolipids in cellular
      signaling.
AB  - Products of glycerolipid and sphingolipid metabolism are now known to fulfill
      second messenger functions in a variety of cellular signaling pathways. Evidence
      for glycerolipid-derived second messengers was first obtained from the
      "phosphatidylinositol cycle," which involves a signal-dependent hydrolysis of
      phosphatidylinositol bisphosphate yielding diacylglycerol and inositol
      trisphosphate. The role of diacylglycerol in the regulation of protein kinase C
      activity and its site of interaction with PKC are now well known. Recently,
      another glycerolipid second messenger, phosphatidic acid, was found to interact
      with the protooncogenic Raf-1 kinase. In cultured cells, a signal-induced
      generation of phosphatidic acid was critical for Raf-1 translocation to the cell
      membrane. Thus, different glycerolipid second messengers appear to regulate
      distinct targets with exquisite specificity. Analogous to the PI cycle, a
      "sphingomyelin cycle" was also found to exist, generating sphingolipid second
      messengers. Ceramide, derived from the agonist-induced hydrolysis of
      sphingomyelin, is a potent biomolecule with effects in multiple cell signaling
      pathways. The steroid hormone progesterone stimulated sphingomyelin hydrolysis in
      Xenopus oocytes. Ceramide, derived from the "sphingomyelin cycle," was sufficient
      for meiotic cell cycle progression in the oocytes. These results demonstrate the
      various effects of lipid-derived second messengers and promise exciting
      discoveries into the roles of lipids in cell signaling.

PMID- 9034166
TI  - Growth factors in the extracellular matrix.
AB  - Much recent research has focused on the study of the expression of growth factor
      genes and on the identification of growth factor signaling mechanisms inside
      cells. However, growth factor signaling can also be regulated outside of cells by
      extracellular matrix proteins and proteolytic enzymes. The ability of
      extracellular proteins to process complex information in the absence of new
      protein synthesis is illustrated in blood clotting and complement pathways. An
      increasing number of growth factors, including IGFs, FGFs, TGF-beta's, and HGF,
      have been found to associate with the extracellular matrix proteins or with
      heparan sulfate. Rapid and localized changes in the activity of these factors can
      be induced by release from matrix storage and/or by activation of latent forms.
      These growth factors, in turn, control cell proliferation, differentiation, and
      synthesis and remodeling of the extracellular matrix. It is therefore likely that
      much of the information processing necessary for construction of complex
      multicellular organisms occurs in the extracellular environment. This suggests
      that extracellular matrix plays a major role in the control of growth factor
      signaling.

PMID- 9034167
TI  - Imprinted genes in liver carcinogenesis.
AB  - Each cell contains both maternal and paternal copies of all genes except those
      that reside on the sex chromosomes. However, because of a phenomenon termed
      genomic imprinting, not all genes are biallelically expressed. Imprinted genes
      play an important role in embryogenesis and recently have also been shown to be
      mechanistically involved in carcinogenesis. The growing list of imprinted genes
      implicated in tumor formation includes both a growth factor gene, insulin-like
      growth factor 2 (IGF2), and a receptor gene, mannose 6-phosphate/insulin-like
      growth factor 2 receptor (M6P/IGF2R). Elevated expression of IGF2 is often found
      in tumors, and loss of imprinting is one mechanism by which its expression is
      deregulated. The M6P/IGF2R functions in the inactivation of the mitogen IGF2 and
      in the activation of the growth inhibitor, transforming growth factor beta.
      Recently, a high frequency of loss of heterozygosity with concomitant mutations
      in the remaining allele has been shown to occur at the M6P/IGF2R locus (i.e.,
      6q26-q27) in both human liver and breast tumors, suggesting that this gene
      functions as a tumor suppressor. Expression of the M6P/IGF2R gene is biallelic in
      most humans but is monoallelic in mice. This species difference in M6P/IGF2R gene
      imprinting provides one plausible explanation for the enhanced sensitivity of
      mice to tumor formation. Furthermore, these findings suggest that species
      differences in the imprinted status of genes mechanistically involved in tumor
      formation should be factored into human carcinogenesis risk assessment models
      when extrapolating results from mice to humans.

PMID- 9034168
TI  - A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint
      proteins.
AB  - Computer analysis of a conserved domain, BRCT, first described at the carboxyl
      terminus of the breast cancer protein BRCA1, a p53 binding protein (53BP1), and
      the yeast cell cycle checkpoint protein RAD9 revealed a large superfamily of
      domains that occur predominantly in proteins involved in cell cycle checkpoint
      functions responsive to DNA damage. The BRCT domain consists of approximately 95
      amino acid residues and occurs as a tandem repeat at the carboxyl terminus of
      numerous proteins, but has been observed also as a tandem repeat at the amino
      terminus or as a single copy. The BRCT superfamily presently includes
      approximately 40 nonorthologous proteins, namely, BRCA1, 53BP1, and RAD9; a
      protein family that consists of the fission yeast replication checkpoint protein
      Rad4, the oncoprotein ECT2, the DNA repair protein XRCC1, and yeast DNA
      polymerase subunit DPB11; DNA binding enzymes such as terminal
      deoxynucleotidyltransferases, deoxycytidyl transferase involved in DNA repair,
      and DNA-ligases III and IV; yeast multifunctional transcription factor RAP1; and
      several uncharacterized gene products. Another previously described domain that
      is shared by bacterial NAD-dependent DNA-ligases, the large subunits of
      eukaryotic replication factor C, and poly(ADP-ribose) polymerases appears to be a
      distinct version of the BRCT domain. The retinoblastoma protein (a universal
      tumor suppressor) and related proteins may contain a distant relative of the BRCT
      domain. Despite the functional diversity of all these proteins, participation in
      DNA damage-responsive checkpoints appears to be a unifying theme. Thus, the BRCT
      domain is likely to perform critical, yet uncharacterized, functions in the cell
      cycle control of organisms from bacteria to humans. The carboxyterminal BRCT
      domain of BRCA1 corresponds precisely to the recently identified minimal
      transcription activation domain of this protein, indicating one such function.

PMID- 9034169
TI  - Interaction of human chagasic IgG with the second extracellular loop of the human
      heart muscarinic acetylcholine receptor: functional and pathological
      implications.
AB  - Circulating antibodies from human and murine chagasic sera are able to interact
      with myocardium-activating neurotransmitter receptors. Here we reported the
      presence of autoantibodies against the second extracellular loop of the human
      heart muscarinic acetylcholine receptors (mAChR) in patients with Chagas' disease
      by using a synthetic 24-mer peptide in immunoblotting and enzyme immunoassay.
      Affinity-purified antipeptide IgG from chagasic patients, similar to monoclonal
      antihuman M2 mAChR, recognized bands with a molecular weight corresponding to the
      cardiac mAChR. The binding was inhibited by the peptide, assessing the
      specificity of the interaction. The antipeptide autoantibody also displayed an
      "agonist-like" activity modifying the intracellular events associated with mAChR
      activation, i.e., decreased contractility, increased cGMP, and decreased cAMP
      production. All of these effects on rat atria by chagasic antipeptide
      autoantibodies resemble the effects of the authentic agonist and those of the
      total polyclonal chagasic IgG, being selectively blunted by atropine and
      neutralized by the synthetic peptide corresponding in aminoacid sequence to the
      second extracellular loop of the human M2 mAChR. A clinical relevance of these
      findings is demonstrated by a strong association between the existence of
      circulating antipeptide autoantibodies in chagasic patients and the presence of
      dysautonomic symptoms, making these autoantibodies a proper early marker of heart
      autonomic dysfunction.

PMID- 9034170
TI  - Cystine levels, cystine flux, and protein catabolism in cancer cachexia, HIV/SIV
      infection, and senescence.
AB  - Patients with skeletal muscle catabolism (cachexia) fail to conserve the skeletal
      muscle protein and release large amounts of nitrogen as urea. Previous studies
      suggest that the threshold for the conversion of amino acids into other forms of
      chemical energy and the concomitant production of urea are regulated by the
      plasma cystine level and hepatic cysteine catabolism. Studies of plasma amino
      acid exchange rates in the lower extremities now show that healthy young subjects
      regulate their plasma cystine level in a process that may be described as
      controlled constructive catabolism. The term controlled describes the fact that
      the release of cystine and other amino acids from the peripheral tissue is
      negatively correlated with (certain) plasma amino acid levels. The term
      constructive describes the fact that the release of cystine is correlated with an
      increase of the plasma cystine level. The regulation of the plasma cystine level
      is disturbed in conditions with progressive skeletal muscle catabolism including
      cancer, HIV infection, and old age. These conditions show also a low plasma
      glutamine:cystine ratio indicative of an impaired hepatic cystine catabolism. In
      HIV+ patients and SIV-infected macaques, a decrease of the plasma cystine level
      was found to coincide with the decrease of CD4+ T cells.

PMID- 9034172
TI  - Insurers agree moratorium on gene data.

PMID- 9034171
TI  - Studies of the renal action of melatonin: evidence that the effects are mediated
      by 37 kDa receptors of the Mel1a subtype localized primarily to the basolateral
      membrane of the proximal tubule.
AB  - The pineal hormone melatonin controls circadian behavior of a variety of organs
      in different species, including humans. However, the precise mechanism (or
      mechanisms) by which this occurs remains largely unknown. At the cellular level
      its effects are believed to be mediated via interaction with specific melatonin
      receptors (MR), which have previously been cloned from human brain (Mel1a) and
      retina (Mel1b). At the tissue level, MR have been investigated primarily through
      empirical definition of specific binding sites, but so far there has been little
      success in biochemical or molecular characterization of native MR. In the kidney,
      there is strong circumstantial evidence that melatonin affects diurnal variations
      in renal function, but relatively little is known about the overall glomerular
      vs. tubular contributions to these effects. The strategy behind the present study
      was to use a panel of peptide-specific antibodies to identify MR proteins in
      various tissues, and from a determination of the intrarenal distribution of MR,
      gain insight into the mechanism by which melatonin might regulate kidney
      function. We used two peptide-specific antibodies directed against different
      regions of Mel1a to identify MR. Our results show that the native Mel1a receptor
      is a 37 kilodalton (kDa) protein in human and rat brain. Further,
      immunofluorescent studies carried out in guinea pig kidney have revealed that
      anti-Mel1a antibody is also localized to the basolateral membrane (BLM) of the
      renal cortical epithelium, especially the early proximal tubule. Immunoblotting
      of purified BLM fractions from guinea pig renal cortex and small intestine using
      the two different peptide-specific antibodies reveals the presence of a single
      peptide-blockable band at 37 kDa. These same BLM fractions also demonstrate the
      presence of high-affinity 2-[125I]iodomelatonin (125I-MEL) binding sites, with
      the pharmacological specificity of binding expected of the Mel1a receptor
      subtype, inhibited by guanosine 5'-O-(3'-thiotriphosphate) (GTPgammaS) and
      pertussis toxin. We conclude that functional MR in guinea pig kidney and small
      intestine are of the Mel1a subtype, and are expressed as 37 kDa proteins
      localized to the BLM and coupled to a pertussis toxin-sensitive G-protein (Gi).
      This localization strongly suggests that the proximal tubule plays a significant
      role in mediating the renal action of melatonin.

PMID- 9034173
TI  - Europe reshuffles its scientific committees following BSE crisis.

PMID- 9034174
TI  - EMBO panel gives biology in Finland a pat on the back...as privatization windfall
      fills research coffers.

PMID- 9034175
TI  - Chair of GMO panel resigns over maize.

PMID- 9034176
TI  - 'Whistleblowers face blast of hostility'.

PMID- 9034177
TI  - White House names AIDS policy director.

PMID- 9034178
TI  - Politicians hamper AIDS prevention, says panel.

PMID- 9034179
TI  - Patent threat to research.

PMID- 9034180
TI  - A crisis in scientific morale.

PMID- 9034181
TI  - Telomeres. Different means to common ends.

PMID- 9034182
TI  - Olfactory adaptation. The nose leads the eye.

PMID- 9034183
TI  - Neurobiology. Memory floxed.

PMID- 9034184
TI  - Asthma. Blocking adenosine with antisense.

PMID- 9034185
TI  - A gene family of silicon transporters.

PMID- 9034186
TI  - Multituberculate and other mammal hair recovered from Palaeogene excreta.
AB  - Evidence of hair from several extinct mammals has been recovered from a rich
      accumulation of fossil excrement from the Late Palaeocene beds of Inner Mongolia,
      China. This highly unusual and previously undocumented depositional occurrence
      consists of hundreds of mammalian carnivore coprolites (fossil faeces) and a
      lesser number of probably raptorial bird regurgitalites (fossil pellets). The
      fossil hair occurs as impressions and natural casts in the extremely fine
      grained, calcareous matrix that cements the skeletal remains within these faecal
      structures and preserves even the cuticular scale pattern on individual hair.
      Hair from at least four mammalian taxa, most notably the multituberculate
      Lambdopsalis bulla, has been identified. This record constitutes the first
      tangible evidence that, along with monotremes and therian mammals,
      multituberculates were hirsuite, and lends support for the presence of this
      mammalian feature in the most recent common ancestor of these three groups.

PMID- 9034187
TI  - Haramiyids and Triassic mammalian evolution.
AB  - Isolated teeth referred to the family Haramiyidae are among the earliest known
      fossil evidence of mammals. First discovered in European Late Triassic deposits a
      century and a half ago, haramiyids have been interpreted as related to
      multituberculates, a diverse and widespread lineage that occupied a rodent-like
      niche from the Late Jurassic to the Early Tertiary. Nonetheless, haramiyid
      relationships have remained enigmatic because the orientation and position of the
      teeth in the upper or lower jaw could not be determined with certainty; even
      their mammalian status has been questioned. The discovery of haramiyid dentaries,
      a maxilla and other skeletal remains in the Upper Triassic of East Greenland
      reveals haramiyids as highly specialized mammals with a novel pattern of puncture
      crushing occlusion that differs dramatically from the grinding or shearing
      mechanisms of other Early Mesozoic mammals.

PMID- 9034188
TI  - DNA antisense therapy for asthma in an animal model.
AB  - Asthma is an inflammatory disease characterized by bronchial hyper-responsiveness
      that can proceed to life-threatening airway obstruction. It is one of the most
      common diseases in industrialized countries, and in the United States accounts
      for about 1% of all healthcare costs. Asthma prevalence and mortality have
      increased dramatically over the past decade, and occupational asthma is predicted
      to be the pre-eminent occupational lung disease in the next decade. Increasing
      evidence suggests that adenosine, an endogenous purine that is involved in normal
      physiological processes, may be an important mediator of bronchial asthma. In
      contrast to normal individuals, asthmatic individuals respond to adenosine
      challenge with marked airway obstruction, and concentrations of adenosine are
      elevated in the bronchoalveolar lavage fluid of asthma patients. We performed a
      randomized crossover study using the dust mite-conditioned allergic rabbit model
      of human asthma. Administration of an aerosolized phosphorothioate antisense
      oligodeoxynucleotide targeting the adenosine A1 receptor desensitized the animals
      to subsequent challenge with either adenosine or dust-mite allergen.

PMID- 9034189
TI  - Mechanism of odorant adaptation in the olfactory receptor cell.
AB  - Adaptation to odorants begins at the level of sensory receptor cells, presumably
      through modulation of their transduction machinery. The olfactory signal
      transduction involves the activation of the adenylyl cyclase/cyclic AMP second
      messenger system which leads to the sequential opening of cAMP-gated channels and
      Ca2+-activated chloride ion channels. Several reports of results obtained from in
      vitro preparations describe the possible molecular mechanisms involved in odorant
      adaptation; namely, ordorant receptor phosphorylation, activation of
      phosphodiesterase, and ion channel regulation. However, it is still unknown
      whether these putative mechanisms work in the intact olfactory receptor cell.
      Here we investigate the nature of the adaptational mechanism in intact olfactory
      cells by using a combination of odorant stimulation and caged cAMP photolysis
      which produces current responses that bypass the early stages of signal
      transduction (involving the receptor, G protein and adenylyl cyclase). Odorant-
      and cAMP-induced responses showed the same adaptation in a Ca2+-dependent manner,
      indicating that adaptation occurs entirely downstream of the cyclase. Moreover,
      we show that phosphodiesterase activity remains constant during adaptation and
      that an affinity change of the cAMP-gated channel for ligands accounts well for
      our results. We conclude that the principal mechanism underlying odorant
      adaptation is actually a modulation of the cAMP-gated channel by Ca2+ feedback.

PMID- 9034190
TI  - A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from
      cells.
AB  - Mammalian cells proteolytically release (shed) the extracellular domains of many
      cell-surface proteins. Modification of the cell surface in this way can alter the
      cell's responsiveness to its environment and release potent soluble regulatory
      factors. The release of soluble tumour-necrosis factor-alpha (TNF-alpha) from its
      membrane-bound precursor is one of the most intensively studied shedding events
      because this inflammatory cytokine is so physiologically important. The
      inhibition of TNF-alpha release (and many other shedding phenomena) by hydroxamic
      acid-based inhibitors indicates that one or more metalloproteinases is involved.
      We have now purified and cloned a metalloproteinase that specifically cleaves
      precursor TNF-alpha. Inactivation of the gene in mouse cells caused a marked
      decrease in soluble TNF-alpha production. This enzyme (called the TNF-alpha
      converting enzyme, or TACE) is a new member of the family of mammalian
      adamalysins (or ADAMs), for which no physiological catalytic function has
      previously been identified. Our results should facilitate the development of
      therapeutically useful inhibitors of TNF-alpha release, and they indicate that an
      important function of adamalysins may be to shed cell-surface proteins.

PMID- 9034191
TI  - Cloning of a disintegrin metalloproteinase that processes precursor tumour
      necrosis factor-alpha.
AB  - Tumour-necrosis factor-alpha (TNF-alpha) is a cytokine that contributes to a
      variety of inflammatory disease states. The protein exists as a membrane-bound
      precursor of relative molecular mass 26K which can be processed by a TNF-alpha
      converting enzyme (TACE), to generate secreted 17K mature TNF-alpha. We have
      purified TACE and cloned its complementary DNA. TACE is a membrane-bound
      disintegrin metalloproteinase. Structural comparisons with other disintegrin
      containing enzymes indicate that TACE is unique, with noteable sequence identity
      to MADM, an enzyme implicated in myelin degradation, and to KUZ, a Drosophila
      homologue of MADM important for neuronal development. The expression of
      recombinant TACE (rTACE) results in the production of functional enzyme that
      correctly processes precursor TNF-alpha to the mature form. The rTACE provides a
      readily available source of enzyme to help in the search for new anti
      inflammatory agents that target the final processing stage of TNF-alpha
      production.

PMID- 9034192
TI  - Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome.
AB  - In eukaryotes, ubiquitin (Ub)-dependent proteolysis is essential for bulk protein
      turnover as well as diverse processes including cell-cycle control,
      differentiation, antigen presentation, and the stress response. Generally,
      multiple ubiquitins are added onto a substrate to form an isopeptide-linked
      'polyubiquitin' chain, which targets substrates for degradation by the 26S
      proteasome. The specificity of Ub-dependent degradation was thought to depend
      primarily on the selection of targets for ubiquitination, but recently we have
      reported evidence for a second level of specificity in which (poly)Ub-protein
      conjugates are partitioned among two fates: degradation of the protein substrate
      by the 26S proteasome; and disassembly by Ub isopeptidase(s) to regenerate the
      protein substrate. Potentially, an isopeptidase could influence degradation by
      'editing' (poly)Ub-protein conjugates according to the extent of ubiquitination
      rather than the structure of the ubiquitination target itself. Here we describe a
      bovine isopeptidase that is well suited to such an editing function because of
      its unique localization and specificity. This enzyme is an intrinsic subunit of
      PA700, the 19S regulatory complex of the 26S proteasome. By disassembling the
      degradation signal from only the distal end of (poly)Ub chains, this isopeptidase
      can selectively rescue poorly ubiquitinated or slowly degraded Ub-protein
      conjugates from proteolysis.

PMID- 9034193
TI  - Control of telomere length by the human telomeric protein TRF1.
AB  - Human telomeres, the nucleoprotein complexes at chromosome ends, consist of
      tandem arrays of TTAGGG repeats bound to specific proteins. In normal human
      cells, telomeres shorten with successive cell divisions, probably due to the
      terminal sequence loss that accompanies DNA replication. In tumours and
      immortalized cells, this decline is halted through the activation of telomerase,
      a reverse transcriptase that extends the telomeric TTAGGG-repeat arrays. Telomere
      length is stable in several immortal human-cell lines, suggesting that a
      regulatory mechanism exists for limiting telomere elongation by telomerase. Here
      we show that the human telomeric-repeat binding factor TRF1 (ref. 8) is involved
      in this regulation. Long-term overexpression of TRF1 in the telomerase-positive
      tumour-cell line HT1080 resulted in a gradual and progressive telomere
      shortening. Conversely, telomere elongation was induced by expression of a
      dominant-negative TRF1 mutant that inhibited binding of endogenous TRF1 to
      telomeres. Our results identify TRF1 as a suppressor of telomere elongation and
      indicate that TRF1 is involved in the negative feedback mechanism that stabilizes
      telomere length. As TRF1 does not detectably affect the expression of telomerase,
      we propose that the binding of TRF1 controls telomere length in cis by inhibiting
      the action of telomerase at the ends of individual telomeres.

PMID- 9034194
TI  - Regulation of telomere length and function by a Myb-domain protein in fission
      yeast.
AB  - Telomeres, the specialized nucleoprotein structures that comprise the ends of
      eukaryotic chromosomes, are essential for complete replication, and regulation of
      their length has been a focus of research on tumorigenesis. In the budding yeast
      Saccharomyces cerevisiae, the protein Rap1p binds to telomeric DNA and functions
      in the regulation of telomere length. A human telomere protein, hTRF (human
      TTAGGG repeat factor) binds the telomere sequence in vitro and localizes to
      telomeres cytologically, but its functions are not yet known. Here we use a
      genetic screen to identify a telomere protein in fission yeast, Taz1p (telomere
      associated in Schizosaccharomyces pombe), that shares homology to the Myb proto
      oncogene DNA-binding domain with hTRF. Disruption or deletion of the taz1+ gene
      causes a massive increase in telomere length. Taz1p is required for the
      repression of telomere-adjacent gene expression and for normal meiosis or
      sporulation. It may be a negative regulator of the telomere-replicating enzyme,
      telomerase, or may protect against activation of telomerase-independent pathways
      of telomere elongation.

PMID- 9034195
TI  - Acute in vitro production of acylation stimulating protein in differentiated
      human adipocytes.
AB  - We have previously shown that in normolipidemic healthy adults, plasma acylation
      stimulating protein (ASP) increases postprandially and is produced in vitro by
      cultured differentiated human adipocytes. The present studies were undertaken to
      examine the influence of specific plasma components on endogenous ASP production
      in cultured human adipocytes. The results demonstrate that neither glucose nor
      fatty acids (over a wide range of concentrations) had any substantial effect on
      ASP production. Insulin increased ASP production up to 2-fold (208% +/- 18%, P <
      0.01). However, the most profound increase in ASP was generated by the addition
      of chylomicrons to the cell culture medium. Chylomicrons (CHYLO) obtained from
      postprandial plasma increased ASP production in a time- and concentration
      dependent manner, producing up to a 150-fold increase in ASP at the highest
      concentration of CHYLO tested (500 microg triacylglycerol/mL medium (P < 0.001)).
      By contrast, very low (VLDL), high (HDL), and low density lipoproteins (LDI) had
      only marginal effects. The effects on ASP parallelled the changes in adipocyte C3
      secretion (the precursor protein of ASP). As with ASP, glucose, oleate, insulin,
      and hepatic lipoproteins (VLDL, LDL, and HDL) had little or no effect on C3
      secretion. In contrast, CHYLO had an even greater effect on C3 secretion than on
      ASP generation. Finally, the effects of CHYLO on generation of ASP and C3 were
      not dependent on lipolysis of CHYLO by lipoprotein lipase (LPL). These results
      are consistent with the changes in plasma ASP seen postprandially, and suggests a
      role of ASP as a positive feedback regulator of triacylglycerol synthesis in
      adipose tissue.

PMID- 9034196
TI  - ApoA-II/apoA-I molar ratio in the HDL particle influences phospholipid transfer
      protein-mediated HDL interconversion.
AB  - Pig plasma phospholipid transfer protein (PLTP) facilitates interconversion of
      both human HDL3 and pig HDL into HDL subpopulations of large and small particles.
      We recently suggested that there are two essential parts in the conversion
      mechanism, i.e., the release of apoA-I and phospholipids and the fusion of apoA-I
      depleted unstable particles. Based on their mass composition and electrophoretic
      mobility in agarose gel, the released apoA-I-containing particles are similar to
      previously described pre beta-HDL particles known as primary acceptors of
      peripheral cholesterol. The aim of this study was to determine whether the
      apolipoprotein composition of HDL regulates the PLTP-mediated conversion process.
      Pig HDL was incubated with increasing amounts of human apoA-II which incorporates
      into pig HDL with a concomitant release of apoA-I and some phospholipids. These
      hybrid pig HDL particles formed were isolated by a combination of
      ultracentrifugation at density 1.21 g/ml and gel filtration. The apoA-II/apoA-I
      molar ratios in the hybrid HDL particles ranged from 0.2 to 7.6 mol/mol. In the
      maximally modified HDL apoA-I was totally substituted by apoA-II. These particles
      were incubated in the presence of purified PLTP and the conversion products were
      isolated and characterized. Both the formation of large particles and the release
      of apoA-I were inhibited by increasing concentrations of apoA-II in the HDL
      particle. The hybrid HDL particles behaved similarly as native pig HDL as
      acceptors of phospholipid from PC-vesicles in the PLTP-assay. This study suggests
      that the apoA-II/apoA-I molar ratio in the HDL particle regulates PLTP-mediated
      HDL interconversion.

PMID- 9034197
TI  - Normal and inhibited cholesterol synthesis in the cultured rat embryo.
AB  - The Smith-Lemli-Opitz syndrome-affected fetus presents a deficiency in delta7
      dehydrocholesterol reductase, the last enzymatic step in the cholesterol
      biosynthesis pathway. Development of the abnormal human fetus takes place in a
      normal environment as the heterozygous mother's cholesterolemia remains normal.
      An animal model for this disease has been obtained from the offspring of pregnant
      rats treated with "distal" inhibitors of delta7-dehydrocholesterol reductase, AY
      9944 or BM15766. In the animal model, embryonic development occurs in a disturbed
      environment characterized by hypocholesterolemia and accumulation of delta7
      dehydrocholesterol and delta8-dehydrocholesterol in the maternal serum. The
      purpose of the present study was to assess, in cultured rat embryos at early
      developmental stages, the relative contributions of exogenous and de novo
      synthesized cholesterol in the total embryonic cholesterol, according to the
      conditions of normal and altered de novo biosynthesis. Cultured rat embryos are
      able to synthesize cholesterol as shown by 13C-incorporation into cholesterol
      from 13C-labeled precursors added to the culture medium. De novo cholesterol
      biosynthesis is altered by addition to the culture medium of AY-9944 which
      inhibits the delta7-dehydrocholesterol reductase and the delta8-delta7-sterol
      isomerase as suggested by the emergence of characteristic aberrant sterols in the
      embryonic tissues. Cholesterol-rich serum used for embryo culture alters the
      pattern in a way that confirms that the rat embryos are able to import exogenous
      cholesterol which down-regulates de novo cholesterol biosynthesis. Exogenous
      cholesterol substitutes for the deficit in a manner efficient enough to prevent
      the embryonic abnormalities induced by AY-9944.

PMID- 9034198
TI  - Characterization of human plasma apolipoprotein E-containing lipoproteins in the
      high density lipoprotein size range: focus on pre-beta1-LpE, pre-beta2-LpE, and
      alpha-LpE.
AB  - We have used two-dimensional gel electrophoresis to separate and characterize
      human plasma apolipoprotein (apo) E-containing lipoproteins in the high density
      lipoprotein (HDL) size range. Lipoproteins were separated from whole plasma by
      electrophoresis (according to charge) in a 0.75% agarose gel, and then in the
      second dimension (according to size) in a 2-15% non-denaturing polyacrylamide
      gradient gel. ApoE-containing lipoproteins were detected by radiography after
      electrotransfer of lipoproteins to nitrocellulose membranes and incubation with
      125I-labeled affinity-purified polyclonal apoE antibody. ApoE-containing
      lipoproteins in the HDL size range had a particle size ranging from 9 to 18.5 nm
      in diameter and could be characterized as having either gamma, pre-beta1-, pre
      beta2- or alpha-electrophoretic mobility (designated gamma-LpE, pre-beta1-LpE,
      pre-beta2LpE, and alpha-LpE respectively). gamma-LpE and a substantial proportion
      of pre-beta1- and pre-beta2-LpE did not co-migrate with apoA-I, apoA-II, apoC
      III, or apoB-100. Subsequent experiments focused on the pre-beta1-LpE, pre
      beta2LpE, and alpha-LpE subfractions, which represented > 95% of apoE in HDL
      sized lipoproteins. Storage of plasma at 4 degrees C or in vitro incubation of
      plasma at 37 degrees C caused a relative decrease in pre-beta1-LpE and increase
      in alpha-LpE. Normolipidemic patients with an apoE 2/2 phenotype tended to have
      increased levels of alpha-LpE, whereas apoE 4/4 subjects tended to have a greater
      proportion of HDL-apoE as pre-beta1-LpE. Decrease in plasma HDL apoE
      concentration after an oral fat load was associated with a reduction in the
      plasma concentration of all HDL-apoE subfractions. These results demonstrate
      that: 1) apoE-containing HDL are heterogeneous in size and charge; 2) pre-beta1
      LpE is a relatively labile HDL subfraction; 3) HDL-apoE subfraction distribution
      is dependent on apoE phenotype; and 4) all apoE-containing HDL subfractions
      participate in the plasma transfer of apoE during the postprandial period.

PMID- 9034199
TI  - Epidermal growth factor-stimulated production of esterified 13(S)
      hydroxyoctadecadienoic acid is associated with tumor suppressor phenotype in
      Syrian hamster embryo fibroblasts.
AB  - Epidermal growth factor (EGF) stimulates the lipoxygenase metabolism of linoleic
      acid to 13(S)-hydroxyoctadecadienoic acid (HODE) in Syrian hamster embryo (SHE)
      fibroblasts. 13(S)-HODE is a potent and specific enhancer of EGF-dependent DNA
      synthesis in normal phenotypic SHE cells (supB+), but is inactive in variant SHE
      cells that have lost tumor suppressor gene function (supB-). EGF activation of
      quiescent SHE cells results in increased levels of 13-HODE esterified in cellular
      phospholipid and triglyceride. Steric analyses suggest that this metabolite is
      generated in part by direct oxygenation of membrane lipids by an n-6
      lipoxygenase. In studies on the uptake and mobilization of 13-HODE in SHE cells,
      we observed EGF to stimulate a time- and dose-dependent incorporation and
      reacylation of the mono-hydroxy linoleate metabolite. The level of 13-HODE uptake
      in supB+ cells is twice that of supB-. Among classes of phospholipids,
      radiolabeled 13-HODE is esterified predominantly into phosphatidylcholine and
      this distribution pattern is similar for both SHE cell lines. Pretreatment of
      cells with the tyrosine kinase inhibitor methyl-2,5-dihydroxycinnamate blocks EGF
      stimulated HODE incorporation. Inhibition of tyrosine phosphatase activity with
      vanadate potentiates HODE uptake in supB+ but not supB- cells. Moreover,
      activation of protein kinase C with phorbol ester stimulates HODE incorporation
      in the supB+ line only. The differential effects of EGF on 13-HODE uptake and
      mobilization in supB+ and supB- cells appear to be related to loss of the tumor
      suppressor phenotype. EGF-stimulated generation of esterified 13-HODE may be an
      important biological process in determining the mechanism and site of HODE
      interaction with the mitogenic signaling pathway.

PMID- 9034200
TI  - Microsomal triglyceride transfer protein in CaCo-2 cells: characterization and
      regulation.
AB  - As microsomal triglyceride transfer protein (MTP) is required for the assembly
      and secretion of apoB-containing lipoproteins by intestinal epithelial cells, the
      characterization and regulation of MTP in human intestinal cells, CaCo-2, was
      studied. CaCo-2 cells express MTP mRNA of 4.2 kb and a 97 kDa subunit of MTP
      protein. Similar to the expression of apoB mRNA, MTP mRNA expression was
      dependent upon cell differentiation and was directly related to the ability of
      the cells to assemble and secrete apoB-containing lipoproteins. MTP mRNA
      expression was highest in fully differentiated cells, with small but detectable
      amounts found in undifferentiated cells. Under conditions of increased apoB
      secretion by oleic acid, phosphatidylcholine, or lysophosphatidylcholine, MTP
      mass, MTP activity, and MTP gene expressions were not altered. In cells treated
      with calcium ionophore or phorbol 12-myristate 13-acetate, no relationship could
      be established between apoB secretion and MTP mRNA or activity. Similarly, in
      cells treated with sphingomyelinase, trifluoperazine, verapamil, okadaic acid,
      vanadate, or monensin, agents that decrease apoB secretion, no corresponding
      decrease in MTP activity or mass was observed. The results suggest that the
      various mediators of apoB secretion alter steps in lipoprotein assembly and
      secretion that are not dependent on MTP activity. CaCo-2 cells have an abundant
      supply of MTP for the assembly of lipoproteins when apoB secretion is stimulated
      by dietary lipids.

PMID- 9034201
TI  - Adipokinetic hormone-induced lipolysis in the fat body of an insect, Manduca
      sexta: synthesis of sn-1,2-diacylglycerols.
AB  - The pathway for the adipokinetic hormone-stimulated synthesis of sn-1,2
      diacylglycerols in the adult Manduca sexta fat body was studied. Adult fat body
      lipids were labeled by feeding 5th instar larvae either with [9,10(n)-3H]oleic
      acid or [1(3)-3H] glycerol and after 32 days insects at the adult stage were
      used. This long-term prelabeling led to labeled fat body acylglycerols in which
      triacylglycerols comprised the main radioactive lipid component (95.5%),
      regardless of the radiolabeled compound used. Because the distribution of
      radioactivity among the lipid classes was very close to the mass distribution of
      the fat body lipid subspecies, it was concluded that homogeneous labeling of fat
      body lipids was obtained. After adipokinetic hormone treatment, an accumulation
      of radioactivity in the sn-1,2-diacylglycerol fraction was the only significant
      change found in the distribution of radioactivity among fat body lipids. The size
      of diacylglycerol pool increased 280% 60 min after adipokinetic hormone
      stimulation, whereas the fatty acid, monoacylglycerol and phosphatidic acid pool
      sizes remained constant. These results support the hypothesis that adipokinetic
      hormone-stimulated synthesis of sn-1,2-diacylglycerol in the fat body involves
      stereospecific hydrolysis of the triacylglycerol stores.

PMID- 9034202
TI  - Dissociation of LPL and LDL: effects of lipoproteins and anti-apoB antibodies.
AB  - We have shown previously that the activity of lipoprotein lipase (LPL), the major
      enzyme responsible for hydrolysis of triglyceride contained in circulating
      lipoproteins, is associated with lipoproteins in postheparin plasma. In other
      studies, microtiter plate assays showed that LPL interaction with low density
      lipoprotein (LDL) and very low density lipoprotein (VLDL) was decreased by
      antibodies to apolipoprotein (apo)B. To test whether antibodies to apoB affected
      LPL-LDL association in solution, two types of assays were performed, gel
      filtration and coprecipitation. First we showed that LPL activity and
      immunoreactive mass co-eluted during gel filtration of normal postheparin plasma,
      approximately with the peak of low density lipoproteins. Then LPL was used for
      gel filtration studies in the presence and absence of LDL and anti-apoB
      monoclonal antibodies. LPL association with LDL was diminished by antibodies to
      the amino-terminal region of apoB; antibodies to the carboxyl-terminal LDL
      receptor binding region of apoB were less effective. LDL binding to LPL
      containing heparin-agarose was also disrupted by the amino-terminal antibodies to
      apoB. To determine the LPL-lipoprotein association in situations in which the
      distribution of plasma lipoproteins was altered, we studied plasma from two types
      of subjects with dyslipidemias. The addition of 125I-labeled LPL to type 1
      postheparin plasma produced two peaks of radioactivity, one peak eluted in the
      void volume of the column (with the chylomicrons) and a second peak eluted just
      prior to the normal elution of low density lipoproteins. In postheparin plasma
      from an abetalipoproteinemic subject, LPL eluted with HDL. We conclude that LPL
      associates primarily with apoB-containing lipoproteins. The reason for this
      appears to be that LPL interacts with the apoB.

PMID- 9034203
TI  - Hypocholesterolemic action of beta-cyclodextrin and its effects on cholesterol
      metabolism in pigs fed a cholesterol-enriched diet.
AB  - To examine the effects of beta-cyclodextrin (BCD), a non-absorbable carbohydrate,
      on lipid metabolism, growing pigs were fed a 0.3% cholesterol-enriched diet for 4
      weeks or this diet containing 5% or 10% BCD. Pigs fed a basal diet without added
      cholesterol or BCD were used as controls. The cholesterol-rich diet induced
      hypercholesterolemia (1.75 vs. 0.84 g/l plasma) due to increased LDL
      concentration, delayed the plasma clearance of vitamin A, enhanced liver
      cholesterol storage, lowered the hepatic activities of LDL-receptors (by 47%) and
      HMG-CoA reductase (by 62%), stimulated cholesterol 7alpha-hydroxylase (x3), and
      accelerated the fecal output of neutral sterols (x4). Addition of BCD to the
      cholesterol-rich diet prevented the elevation of plasma cholesterol due to
      dietary cholesterol excess. Moreover, BCD produced a dose-dependent effect in
      reducing liver cholesterol storage, stimulating hepatic cholesterogenesis,
      increasing the proportion of primary bile acids in bile and in feces, and the
      fecal loss of neutral sterols and bile acids. Pigs receiving 10% BCD thus
      differed markedly from controls, especially for HMG-CoA reductase and cholesterol
      7alpha-hydroxylase hepatic activities (x5), and fecal output of total bile acids
      (x3) and hyocholic acid (x20), and their overall cholesterol synthesis was higher
      (+50%), despite the abundant dietary cholesterol. Owing to the property of BCD to
      bind cholesterol and bile acids in vitro, these results suggest that this
      resistant carbohydrate accelerates body cholesterol turnover by reducing
      cholesterol absorption, increasing cholesterol and bile acid synthesis, and
      altering the action of the intestinal microflora.

PMID- 9034204
TI  - Cholesterol deposition in macrophages: foam cell formation mediated by
      cholesterol-enriched oxidized low density lipoprotein.
AB  - Oxidized low density lipoprotein (LDL) is thought to mediate the transformation
      of macrophages to cholesterol-rich foam cells. Yet convincing evidence for this
      process is lacking in vitro. We suggest that oxidized LDL-mediated foam cell
      formation is not seen in vitro because the cholesteryl ester content of LDL
      particles (oxidized in the presence of transition metals) is dramatically
      reduced. Thus, if oxidized LDL could be cholesterol-enriched prior to its
      addition to macrophages, this lipoprotein would be made more capable of inducing
      the cellular deposition of cholesteryl esters. When we enriched cupric sulfate
      oxidized LDL with cholesterol by incubation of this lipoprotein with unesterified
      cholesterol/phosphatidylcholine liposomes and added it to mouse peritoneal
      macrophage cultures, we found that: a) the enrichment of oxidized LDL with
      cholesterol did not alter the extent of oxidized LDL degradation; b) the cells
      accumulated massive amounts of cholesteryl ester (148 microg/mg cell protein) and
      unesterified cholesterol (260 microg/mg cell protein) after 24 h of incubation;
      and c) Sephacryl S-1000 chromatography of the cholesterol-enriched oxidized LDL
      verified the formation of large oxidized LDL-unesterified
      cholesterol/phosphatidylcholine complexes. These results demonstrate that
      oxidized LDL, when cholesterol-enriched, can mediate the formation of macrophage
      foam cells in culture

PMID- 9034205
TI  - Transcriptional and post-transcriptional regulation of LDL receptor gene
      expression in PMA-treated THP-1 cells by LDL-containing immune complexes.
AB  - We have previously shown that uptake of low density lipoprotein-containing immune
      complexes (LDL-IC) by human monocyte-derived macrophages led to the
      transformation of these cells into foam cells and induced a paradoxical increase
      in receptor-mediated binding of 125I-labeled LDL due to an increase in the number
      of LDL receptors (LDL-R). The same metabolic changes are also observed in PMA
      treated THP-1 cells after incubation for 2 h with 150 microg/ml of immune
      complexes containing either native, oxidized (ox), or malondialdehyde (mda) LDL.
      After stimulation, PMA-treated THP-1 cells showed not only a 40-fold increase in
      125I-labeled LDL binding but also a 40-fold increase in the immunoreactive LDL-R
      protein, confirming that the increase in LDL binding is due to an increase LDL-R
      number. In this study we have investigated, in PMA-treated THP-1 cells, the
      regulatory mechanism(s) responsible for the increased receptor-mediated binding
      of LDL induced by LDL-IC. By Northern blot and nuclear run-on analysis we have
      shown transcriptional activation of the LDL-R gene with a 7-fold increase in the
      LDL-R mRNA level in LDL-IC stimulated cells. Due to the marked difference between
      the increase in LDL-R mRNA and LDL-R protein, we estimated LDL-R mRNA stability
      using a inhibitor chase method and have shown that LDL-IC did not alter the LDL-R
      mRNA stability in THP-1 cells. We have also demonstrated, using cycloheximide as
      a inhibitor of protein synthesis, that the marked increase in LDL-R protein
      observed in LDL-IC-stimulated THP-1 cells resulted from de novo synthesis of LDL
      R protein. To determine whether the increase in transcriptional activity of the
      LDL-R gene was secondary to changes in the cholesterol regulatory pool we
      performed experiments in which the cell cholesterol content was modified by the
      addition of either 25-hydroxycholesterol and mevalonate or inhibitors of ACAT
      activity (SA-58035 and progesterone). These experiments showed that the enhanced
      LDL-R expression was not affected by the addition of any of the above compounds.
      In conclusion, LDL-IC induced both transcriptional and post-transcriptional
      activation of the LDL-R gene in PMA-treated THP-1 cells and this induction was
      independent of the free cholesterol content of these cells.

PMID- 9034206
TI  - Heterozygosity for apolipoprotein A-I(R160L)Oslo is associated with low levels of
      high density lipoprotein cholesterol and HDL-subclass LpA-I/A-II but normal
      levels of HDL-subclass LpA-I.
AB  - We studied a Norwegian patient and his family, who presented with low HDL
      cholesterol. DNA sequence analysis of the apoA-I gene revealed heterozygosity for
      a mutation in the apoA-I gene that causes a leucine for arginine replacement at
      residue 160. Compared to unaffected family members, heterozygous carriers of apoA
      1 (R160L)Oslo had 60-70% lower mean levels of HDL-cholesterol, 50-60% lower mean
      levels of apoA-I and 70-80% lower levels of apoA-II. Moreover, the serum
      concentration of the apoA-II-containing HDL-subclass LpA-I/A-II was decreased by
      70% whereas the concentration of the apoA-II-free HDL-subclass LpA-I did not
      differ from that in unaffected family members. The decrease of LpA-I/A-II was
      associated with the lack of large LpA-I/A-II. ApoA-I(R160L)Oslo was present at
      increased concentrations relative to normal apoA-I in plasma, HDL3, and LpA-I.
      However, only trace amounts of the variant isoform were detectable in
      immunopurified LpA-I/A-II. Pre beta1-LpA-I contained normal and variant apoA-I
      isoforms. We conclude that the failure of apoA-I(R160L)Oslo to form LpA-I/A-II
      causes low HDL-cholesterol in heterozygous carriers of this apoA-I variant.

PMID- 9034207
TI  - Norepinephrine-induced lipolysis in rat fat cells from visceral and subcutaneous
      sites: role of hormone-sensitive lipase and lipid droplets.
AB  - Norepinephrine-induced lipolysis was examined in visceral (epididymal and
      omental) and subcutaneous (abdominal and femoral) fat cells in rats. Hormone
      induced lipolysis was considerably higher in the visceral fat cells than in the
      subcutaneous cells. A higher hormone-sensitive lipase (HSL) activity was present
      in the visceral than in the subcutaneous fat cells. Endogenous lipid droplets
      were prepared from rat visceral (epididymal and omental) and subcutaneous
      (abdominal and femoral) fat cells and norepinephrine-induced lipolysis was
      examined in a cell-free system consisting of the lipid droplets prepared from fat
      cells from each site and a fixed amount of HSL from rat epididymal adipose
      tissue. In this cell-free system, norepinephrine induced a higher rate of
      lipolysis with lipid droplets from the visceral than from the subcutaneous fat
      cells. These findings suggest that the difference in norepinephrine-induced
      lipolysis between visceral and subcutaneous fat cells may be due to the
      differences in HSL activity and lipid droplet character at each site.

PMID- 9034208
TI  - Fractional esterification rate of cholesterol in high density lipoprotein is
      correlated with low density lipoprotein particle size in children.
AB  - Small low density lipoprotein (LDL) particles are thought to be more atherogenic
      than larger LDL particles, although this association may depend on plasma
      triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent
      coronary artery disease (CAD), it may be useful to understand risk factors during
      childhood and adolescence. In the present study, we evaluated low density
      lipoprotein particle size (LDL-size) by 2-16% gradient gel electrophoresis in 70
      healthy children (30 boys and 40 girls) along with conventional lipid and
      lipoprotein parameters which are thought to affect LDL-size. The fractional and
      molar esterification rates (FER and MER) of cholesterol in plasma and HDL were
      also determined. As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and
      apoA-I were closely associated with LDL-sizes in both sexes (boys: r = -0.694,
      0.708 and 0.701, girls: r = -0.579, 0.551 and 0.539, P < 0.001). However, a
      closer association was found between FER in HDL (FER(HDL)) and LDL-size (boys: r=
      -0.874, girls: r= -0.642, P < 0.001). In a stepwise multiple regression analysis,
      FER(HDL) alone accounted for 76% and 41% of the variability in LDL-size in boys
      and girls, respectively. MER in HDL accounted for additional 4% and 19% in boys
      and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I
      had no significant additional effects. Thus, the determination of FER(HDL) is
      useful to predict the particle size of LDL in children.

PMID- 9034209
TI  - Polyunsaturated fatty acid metabolism in retinal and cerebral microvascular
      endothelial cells.
AB  - Docosahexaenoic acid (22:6n-3), an n-3 essential fatty acid derived from
      elongation and desaturation of linolenic acid (18:3n-3), is found in abundant
      proportion in the brain and the retina. It is generally assumed that the liver is
      the major source of 22:6n-3 for these organs, although some retinal and cerebral
      cells, such as retinal pigment epithelium (Wang and Anderson, 1993. Biochemistry.
      32:13703-13709) and brain astrocytes (Moore et al. 1991. J. Neurochem. 56:518
      524) have the ability to produce 22:6n-3. The aim of the present study was to
      determine whether retinal and cerebral microvascular endothelium could synthesize
      22:6n-3. After incubation of both cultured bovine retinal and rat cerebral
      endothelial cells with [3-14C] 22:5n-3 in presence of serum, radioactivity was
      primarily recovered in 20:5n-3, indicating active retroconversion reactions in
      both tissues. However, 22:6n-3, 24:5n-3, and 24:6n-3 were also labeled. All of
      these metabolites were released in the medium as free fatty acids. Retinal
      endothelial cells preferentially released labeled 24-carbon metabolites, whereas
      cerebral endothelial cells released relatively more 20:5n-3 and 22:6n-3. With
      heat-inactivated serum or no serum, both endothelial cell preparations showed
      relatively higher retroconversion levels. However, in serum-deprived cells, the
      elongation/desaturation pattern was affected in retinal cells only, with an
      accumulation of 24:5n-3 relative to a decrease of 24:6n-3 and 22:6n-3. Fatty acid
      composition analyses revealed a decrease in long-chain polyunsaturated n-6 and n
      3 fatty acids in retinal cells maintained in inactivated serum compared to normal
      serum, while no change was found in cerebral cells. Taken together, these results
      suggest that 1) the synthesis of 22:6n-3 by both retinal and cerebral endothelial
      cells is independent of a delta4-desaturase; 2) retinal and cerebral endothelia
      could be a source of 22:6n-3 for the retina and the brain, respectively; and 3)
      retinal endothelial delta6-desaturase, which converts 24:5n-3 to 24:6n-3, could
      be stimulated by serum components.

PMID- 9034210
TI  - Influence of ganglioside GM3 and high density lipoprotein on the cohesion of
      mouse brain tumor cells.
AB  - Previous findings with various murine tumor cell lines suggest an association
      between ganglioside GM3 and cell cohesive properties. The influence of GM3 on
      cohesion was studied in two mouse brain tumor cell lines: ependymoblastoma (EPEN)
      and CT-2A. In culture, the EPEN cells grow as islands and contain GM3 as the only
      ganglioside, whereas the CT-2A cells grow as a fusiform cell monolayer and
      contain GM2, GM1, and GD1a as major gangliosides and low amounts of GM3. To
      examine the role of GM3 in cohesion, both cell lines were treated with 1) C.
      perfringens neuraminidase, 2) anti-GM3 monoclonal antibody (mAb DH2), or 3) were
      grown in serum-free medium. All three treatments caused a significant increase in
      the number of non-cohesive and protoplasmic process-bearing cells for the EPEN,
      but had no effect on the morphology of the CT-2A cells. The neuraminidase
      treatment removed GM3 from both cell lines and caused a significant accumulation
      of GM1 in the CT-2A cells. EPEN cell cohesion and GM3 content returned to control
      levels after removal of neuraminidase. EPEN cell cohesion was restored in serum
      free medium with added high density lipoprotein (HDL). The HDL effect on the EPEN
      cell cohesion was dose-dependent and was not seen with other lipoproteins. We
      suggest that EPEN cell cohesion could involve an interaction between
      extracellular HDL, acting as a bridge, and GM3 molecules on opposing cell
      surfaces.

PMID- 9034211
TI  - Quantitative analysis of plasma acylcarnitines using gas chromatography chemical
      ionization mass fragmentography.
AB  - A stable isotope dilution gas chromatography chemical ionization mass
      spectrometry (GC-CI-MS) method was developed for the quantitative profiling of
      plasma acylcarnitines. The clean-up procedure was comprised of a solid-phase
      cation exchange extraction using PRS-columns from which the acylcarnitines were
      eluted with a barium chloride solution. Isolated acylcarnitines were transformed
      into acyloxylactones and analyzed by positive GC-CI-MS using isobutane as
      reactant gas. The selected monitoring of a common ion at m/z [85]+ and the
      protonated molecular ion enabled a selective and sensitive detection of all C2
      C18 acylcarnitines. An accurate quantitation was achieved by the use of stable
      isotope-labeled internal standards (C2-C18) and acylcarnitines could be analyzed
      in the sub-nanomolar range. Control values for C2-C18 acylcarnitines in plasma
      were established. Concentrations ranged from 0.02 micromol/L for C14
      acylcarnitine to 4.90 micromol/L for C2-acylcarnitine. The diagnostic suitability
      of the method was demonstrated for patients with medium-chain acyl-CoA
      dehydrogenase deficiency and very long-chain acyl-CoA dehydrogenase deficiency.

PMID- 9034212
TI  - Measurement of bile acid synthesis by three different methods in
      hypertriglyceridemic and control subjects.
AB  - In hypertriglyceridemic subjects, bile acid synthesis measured by isotope
      dilution is consistently higher than synthesis measured by fecal acidic sterol
      output. To see which of these two measurements was the more accurate, we compared
      them to synthesis measured by release of 14CO2 from [26-14C]cholesterol. In 14
      hypertriglyceridemic subjects, mean +/- SEM synthesis by the CO2 method was 1540
      +/- 199 micromol/day, similar to values by fecal acidic sterol output (1660 +/-
      295). Both were significantly lower than values by isotope dilution (2520 +/-
      269, P = 0.0001 and 0.0015, respectively). In 12 normolipidemic controls, mean +/
      SEM synthesis by the CO2 method was 1230 +/- 189 micromol/day, nearly identical
      to synthesis by fecal acidic sterols (1220 +/- 187). Both were somewhat less than
      synthesis by isotope dilution (1590 +/- 133), but in neither case were the
      differences statistically significant (P = 0.098 and 0.129, respectively). In 3
      hypertriglyceridemic subjects, synthesis measured by the CO2 method increased by
      42%, 44%, and 109% after 4 days of bile sampling, suggesting that the isotope
      dilution procedure actually stimulated synthesis. Fraction of bile acid not
      absorbed during daily enterohepatic cycling was 8.4 +/- 1.4% in the
      hypertriglyceridemic subjects compared to 4.9 +/- 0.8% in the normolipidemic
      controls (P = 0.037). We suggest that during sampling of bile for isotope
      dilution measurements, the terminal ileum is abruptly presented with a large
      bolus of unadulterated bile acid, both because of artificial stimulation of
      gallbladder contraction and return of surplus collected bile to the subject. In
      hypertriglyceridemia, because of an inefficient absorptive mechanism, this may
      result in unusual loss of bile acid with consequent stimulation of bile acid
      synthesis.

PMID- 9034213
TI  - What is the NIGMS doing to help smooth out the irregularities in funding for
      ongoing research programs that almost inevitably occur over time in today's
      fiscal climate?

PMID- 9034214
TI  - Tumor vascular endothelium: barrier or target in tumor directed drug delivery and
      immunotherapy.
AB  - The therapy of solid tumors with conventional chemotherapeutics, drug delivery
      preparations and immunomodulatory agents directed against the tumor cells is
      corrupted by a major barrier presented by the tumor vasculature. Permeability of
      the tumor blood vessels for transport of small molecules and macromolecular drug
      carrier conjugates is only sufficient in the blood vessels at the tumor-host
      interface. Downregulation of the expression of adhesion molecules, required for
      the facilitation of immune cell recruitment, by the tumor vascular endothelium
      results in an escape of the tumor from host defence. New therapeutic approaches
      for the treatment of solid tumors are aimed at the tumor vasculature, either at
      the endothelial cells themselves or at basement membrane or tumor stroma
      components. Angiogenesis can be directly blocked with angiogenesis inhibitors,
      while angiogenesis related factors can serve as tumor vasculature specific
      epitopes for drug delivery strategies. Some glycoproteins expressed by tumor
      endothelial cells or present in the basement membrane and tumor stroma are also
      potential tumor selective targets. Therapeutic modalities that are suitable for
      site specific delivery are agents that increase tumor accumulation of (targeted)
      chemo/radiotherapeutics through increasing tumor vascular permeability. The
      observation that for tumor growth the blood supply is a limiting factor, led to
      the development of strategies to inhibit angiogenesis or block the tumor blood
      flow. Manipulation of the expression of endothelial cell adhesion molecules by
      selectively delivering modulatory agents at or in the tumor vascular endothelial
      cells may induce (bispecific antibody mediated) host defense activity directed
      against the tumor cells.

PMID- 9034215
TI  - Esterase-sensitive cyclic prodrugs of peptides: evaluation of a phenylpropionic
      acid promoiety in a model hexapeptide.
AB  - PURPOSE: To evaluate a cyclic phenylpropionic acid prodrug of a model hexapeptide
      (H-Trp-Ala-Gly-Gly-Asp-Ala-OH) as a novel approach to enhance the membrane
      permeation of a peptide and stabilize it to metabolism. METHODS: Conversion to
      the linear hexapeptide was studied at 37 degrees C in HBSS, pH 7.4, and in
      various biological milieus having measurable esterase activities. Transport and
      metabolism characteristics were assessed using the Caco-2 cell culture model.
      RESULTS: In aqueous buffered solution, pH 7.4, the cyclic prodrug degraded
      quantitatively (t1/2 = 1795 +/- 289 min) to the linear hexapeptide and the
      lactone. Substantially faster degradation of the cyclic prodrug was observed in
      90% human plasma (t1/2 = 508 +/- 24 min), and in homogenates of Caco-2 cells
      (t1/2 = 940 +/- 13 min), the rat intestinal mucosa (t1/2 = 1286 +/- 32 min), and
      rat liver (t1/2 = 840 +/- 42 min). Pretreatment of these biological media with
      paraoxon significantly decreased the degradation rate of the prodrug. When
      applied to the apical side of Caco-2 cell monolayers, the cyclic prodrug was
      significantly more stable than the hexapeptide and at least 71-fold more able to
      permeate (P(app) = 1.21 +/- 0.12 X 10(-7) cm/s) than was the parent peptide
      (P(app) < or = 0.17 x 10(-8) cm/s). In the presence of 0.1 mM palmitoyl-DL
      carnitine, the transport rate of the cyclic prodrug (P(app) = 2.19 X 10(-6) cm/s)
      was 1250-fold greater than that of the linear hexapeptide. CONCLUSIONS:
      Preparation of a cyclic peptide using a phenylpropionic acid promoiety reduced
      the lability of the peptide to peptidase metabolism and substantially increased
      its permeation through biological membranes. In various biological media the
      parent peptide was released from the prodrug by an apparent esterase-catalyzed
      reaction, sensitive to paraoxon inhibition.

PMID- 9034216
TI  - Influence of fluorescent labelling of polystyrene particles on phagocytic uptake,
      surface hydrophobicity, and plasma protein adsorption.
AB  - PURPOSE: To investigate the influence of fluorescent labelling of polystyrene
      particles on phagocytic uptake, surface hydrophobicity and protein adsorption.
      METHODS: Phagocytic uptake was analysed using chemiluminescence. Hydrophobicity
      was quantified by adsorption measurements of a hydrophobic dye. Protein
      adsorption was evaluated by two-dimensional electrophoresis. RESULTS:
      Commercially available fluorescently labelled particles showed marked differences
      when compared to unlabelled particles: phagocytic uptake and surface
      hydrophobicity of labelled particles were diminished. Also the plasma protein
      adsorption pattern was found to be different from the unlabelled particles: for
      example, the amount of fibrinogen adsorbed was strongly reduced on the labelled
      particles. On the other hand, some unknown proteins could be detected on the
      fluorescently marked particles. In contrast, plain polystyrene particles and
      labelled ones could be successfully synthesised by Paulke which did not show any
      considerable differences in phagocytic uptake, surface hydrophobicity and protein
      adsorption. Polysorbate 20 added as stabilizer to particle suspensions led to
      completely different behaviour of the particles: the particles showed altered
      protein adsorption patterns, dominated by immunoglobulins and especially by
      apolipoproteins. Furthermore, these particles were not phagocytized at all.
      CONCLUSIONS: Surface hydrophobicity and phagocytic uptake in vitro as well as the
      interactions with plasma proteins of commercially available polystyrene particles
      were strongly affected by fluorescent labelling. Particles synthesised by Paulke
      remained unchanged after labelling. The results show the importance of thorough
      surface characterization for using particles in test systems in vitro and in
      vivo.

PMID- 9034218
TI  - Tensioactivity and supramolecular organization of the palmitoyl prodrug of
      timolol.
AB  - PURPOSE: To improve the bioavailability of the ocular drug timolol by
      facilitating its transport through the cornea, an amphiphilic prodrug was
      synthesized via the addition of a palmitic chain by esterification. The present
      study was undertaken to investigate the physicochemical and tensioactive
      properties of the prodrug. METHODS: The amphiphilic properties of the prodrug
      were firstly investigated by the Wilhelmy plate method. The textures generated by
      the supramolecular organizations of the ester were visualized by optical
      microscopy. RESULTS: The prodrug clearly decreased the surface tension. Optical
      microscopy provided excellent evidence for the existence of lyotropic liquid
      crystalline phases: two isotropic but organized phases and a birefringent
      lamellar phase. CONCLUSIONS: The results from the ensemble of studies undertaken
      to determine the amphiphilic properties of the prodrug were all in accord with
      its ability to form liquid crystalline phases. The liquid crystalline state of
      the prodrug is believed to introduce a delay in the drug pharmacological effect.

PMID- 9034217
TI  - Assembly and dissociation of human insulin and LysB28ProB29-insulin hexamers: a
      comparison study.
AB  - PURPOSE: Investigations into the kinetic assembly and dissociation of hexameric
      LysB28ProB29-human insulin (LysPro), a rapid-acting insulin analog produced by
      the sequence inversion of amino acids at positions B28 and B29, were designed to
      explain the impact that the sequence inversion has on the formulation and
      pharmacokinetics of the insulin analog. METHODS: The kinetics of phenolic ligand
      binding to human insulin and LysPro were studied by stopped-flow spectroscopy.
      The kinetics of R6 hexamer disruption were studied by extraction of Co(II) with
      EDTA. RESULTS: Phenolic ligand binding to human insulin yielded rate constants
      for a fast and slow phase that increased with increasing ligand concentration and
      are attributed to the T6 --> T3R3 and T3R3 --> R6 transitions, respectively.
      However, the kinetics of phenolic ligand binding with LysPro was dominated by
      rates of hexamer assembly. The kinetic differences between the insulin species
      are attributed to alterations at the monomer-monomer interface in the dimer
      subunit of the LysPro analog. The extraction of Co(II) from both hexameric
      complexes by EDTA chelation is slow at pH 8.0 and highly dependent on ligand
      concentration. Cobalt extraction from LysPro was pH dependent. Of the various
      phenolic ligands tested, the relative affinities for binding to the human and
      LysPro hexamer are resorcinol > phenol > m-cresol. CONCLUSIONS: The extraction
      data support the formation of an R6-type LysPro hexamer under formulation
      conditions, i.e., in the presence of divalent metal and phenolic ligand, that is
      similar in nature to that observed in insulin. However, the formation kinetics of
      LysPro identify a radically different monomeric assembly process that may help
      explain the more rapid pharmacokinetics observed with the hexameric formulation
      of LysPro insulin relative to human insulin.

PMID- 9034219
TI  - In vitro human skin barrier modulation by fatty acids: skin permeation and
      thermal analysis studies.
AB  - PURPOSE: This study aims to elucidate the skin permeation enhancement and the
      skin perturbation effects of a number of fatty acids, i.e. straight-chain
      saturated (SFA), monounsaturated (MUFA) and polyunsaturated acids (PUFA).
      METHODS: The skin permeation enhancement effects were studied using human stratum
      comeum (SC) and p-aminobenzoic acid (PABA) as a model permeant. The fatty acids
      in propylene glycol (FA/PG) were applied according to a pre-treatment/co
      treatment protocol. The perturbation effects were studied using differential
      thermal analysis (DTA) on SC after pretreatment with FA/PG. RESULTS: SFA with 6
      to 12 carbons exhibit a parabolic correlation between enhancement effect and
      chain-length, with a maximum at nonanoic-decanoic acids (with 9 and 10 carbons).
      Nonanoic and decanoic acids exert barely noticeable effects on the thermal
      behaviour of SC, suggesting that they easily mix with the skin lipids. All cis-6
      , 9-, 11- or 13-octadecenoic acids (MUFA) enhance the permeation of PABA to the
      same extent. DTA revealed that the cis-9- and 13-isomers form a separate domain
      containing mostly the pure fatty acids within the SC lipids and suppress the
      lipid transitions at 70 degrees/80 degrees C. PUFA--linoleic (LA), alpha
      linolenic (ALA) and arachidonic acids--enhance PABA permeation stronger than MUFA
      but additional double bonds do not further increase the degree of enhancement. LA
      and ALA form separate domains but do not completely suppress the SC lipid
      transitions at 70 degrees/80 degrees C. Increase in the enthalpy changes of 70
      degrees/80 degrees transitions linearly correlates to the decrease in the
      permeability coefficients, suggesting that an increased perturbation of the skin
      lipids not necessarily has to yield an increased PABA permeation. CONCLUSIONS:
      The enhancement effects of fatty acids on the PABA penetration through SC are
      structure-dependent, associated with the existence of a balance between the
      permeability of pure fatty acids across SC and the interaction of the acids to
      skin lipids.

PMID- 9034220
TI  - Selegiline percutaneous absorption in various species and metabolism by human
      skin.
AB  - PURPOSE: A Selegiline Transdermal System (STS) is under development for
      indications which may not be optimally or safely treated with oral selegiline.
      Studies were conducted to evaluate the in vitro penetration and skin metabolism
      of selegiline in order to better understand the toxicological findings and the
      observed plasma levels of selegiline and its metabolites in animals and man.
      METHODS: In vitro penetration studies were conducted in four different species
      (male hairless mice, male and female rats, female dog and male Micropig) and
      compared to human skin. In another study, viable human skin was used to estimate
      the extent of metabolism of selegiline by human skin using Franz diffusion cells.
      RESULTS: Results indicated that female dog and male Micropig skin were reasonable
      animal models for 24 hour in vitro selegiline penetration through human skin.
      Penetration of selegiline through rat skin and hairless mouse skin was 2-fold and
      3-fold higher than through human skin, respectively. Metabolism was negligible in
      human skin. Selegiline metabolites (L-methamphetamine and N-desmethylselegiline
      but not L-amphetamine) were detected at all time points but the extent of
      selegiline metabolism was negligible. The cumulative 24 hour in vitro selegiline
      permeation from a 1.83 mg/cm2 STS through human skin was 5.0 mg. This was similar
      to the in vivo permeation in humans as assessed by residual patch analysis.
      CONCLUSIONS: The similarity of dog and human skin permeation results support the
      use of the dog as a species for evaluating the toxicology of transdermally
      administered selegiline. Selegiline is not metabolized cutaneously and hence the
      metabolic profile following STS administration is likely due to hepatic
      metabolism only.

PMID- 9034222
TI  - Drug reservoir composition and transport of salmon calcitonin in transdermal
      iontophoresis.
AB  - PURPOSE: The aim of the work was to study iontophoretic transdermal
      administration of salmon calcitonin (sCt) in rabbits, with particular attention
      to drug reservoir composition. A dry sCt disc, to be dissolved on the application
      site, was used for preparing the reservoir for transdermal iontophoresis. As a
      reference drug reservoir, a pad wetted with drug solution was used. METHODS:
      Experiments were done in rabbits depositing 100 IU of salmon calcitonin on skin
      and applying anodal iontophoresis. Serum calcium concentration was measured
      during iontophoresis, passive diffusion and after i.v. administration. Parameters
      such as pH value and reservoir type were examined. RESULTS: Transdermal
      iontophoresis of sCt elicited a decrease in the serum calcium level, whereas, in
      the absence of electric current, no significant fall was measured. Using the
      reservoir prepared from drug solution, anodal iontophoresis at pH 4.2 was more
      effective than at pH 7.4, probably due to higher sCt net positive charge. Using
      the reservoir prepared from dry disc, similar kinetics and extent of drug effect
      were observed at both pH values. The reservoir prepared from solid drug deposit
      concentrated sCt next to the skin. CONCLUSIONS: Anodal iontophoresis for
      transdermal calcitonin administration shows therapeutical applicability. The type
      of reservoir is an important parameter affecting sCt transdermal iontophoresis.

PMID- 9034221
TI  - In vivo evaluation of acyclovir prodrug penetration and metabolism through rat
      skin using a diffusion/bioconversion model.
AB  - PURPOSE: In order to evaluate the in vivo penetration of prodrugs which undergo
      metabolism in skin, we analyzed the in vivo penetration profiles of acyclovir
      prodrugs based on a two-layer skin diffusion model in consideration of metabolic
      process. METHODS: Acyclovir prodrugs (e.g., valerate, isovalerate and pivarate)
      were used as model prodrugs and the amounts excreted in urine were measured after
      percutaneous application. In vivo penetration profiles were then estimated by
      employing a deconvolution method and the penetration of acyclovir prodrugs was
      analyzed using a diffusion model. Subsequently, diffusion, partitioning and
      metabolic parameters were compared under in vitro and in vivo conditions.
      RESULTS: Although total penetration amounts at the end of the experiment were
      similar for the three prodrugs, the ratio of intact prodrug to total penetration
      amount differed significantly. Moreover, the excretion and absorption profiles
      were also very different for each prodrug. Enzymatic hydrolysis rate constants
      calculated under in vivo conditions were considerably larger than those obtained
      in the skin homogenate and in vitro penetration experiments. CONCLUSIONS: The
      present skin diffusion/bioconversion model combined with computer analysis
      enables us to comprehensively account for diffusion, partitioning and metabolism
      during in vivo percutaneous absorption. Nevertheless, different enzymatic
      hydrolysis rate constants obtained under both in vivo and in vitro conditions
      demonstrate the difficulty of obtaining accurate values for in vivo enzymatic
      activity from related in vitro experiments.

PMID- 9034223
TI  - Extrahepatic ischemia-reperfusion injury reduces hepatic oxidative drug
      metabolism as determined by serial antipyrine clearance.
AB  - PURPOSE: All transplanted solid organs experience some degree of ischemia
      reperfusion (I-R) injury. This I-R injury can contribute to graft dysfunction
      which stems in part from the acute phase response and a resultant host of
      cytokines. Recent evidence suggests that organs remote to the site of I-R injury
      can be affected by circulating cytokines originating from these I-R injuries.
      Since many of these acute phase cytokines inhibit hepatic cytochrome P-450 (CYP)
      enzymes, we chose to investigate whether extrahepatic I-R injuries could
      influence hepatic oxidative drug metabolism. METHODS: Fifteen dogs were divided
      into three surgical groups: (I) sham I-R; (II) bilateral normothermic renal I-R;
      and (III) normothermic intestinal I-R. Antipyrine (AP) was selected as a model
      substrate and administered intravenously at a dose of 10 mg/kg. AP serum
      concentrations were determined by HPLC and cytokine activity (IL-1, IL-6, and
      TNFalpha) was measured via bioassay. Serial AP clearance and serum cytokine
      concentrations were determined 3 days prior to and at 4 hr, 24 hr, 3 days and 7
      days after surgery. Hematology and blood chemistries were monitored throughout
      the study period. RESULTS: AP clearance was significantly reduced in groups II
      and III at 4 and 24 hrs post-l-R injury, while AP binding and apparent volume of
      distribution were unaffected. Peak levels of TNF and IL-6 activity occurred at 1
      and 4 hours, respectively. IL-I activity was not detected in any group. AP
      clearance correlated strongly to circulating levels of IL-6 (r = -0.789, p =
      0.0002). CONCLUSIONS: Our findings indicate that extrahepatic I-R injury can
      affect hepatic oxidative drug metabolism and this effect is mediated in part by
      circulating cytokines.

PMID- 9034224
TI  - Interaction between polyalkylcyanoacrylate nanoparticles and peritoneal
      macrophages: MTT metabolism, NBT reduction, and NO production.
AB  - PURPOSE: The nature of interactions between macrophages and drug carriers is of
      primordial importance either in the design of more effective therapeutic
      strategies for macrophage-associated pathogenesis or in establishing new
      approaches for pharmacological action avoiding macrophages. METHODS:
      Polyalkylcyanoacrylate nanoparticles (PMCA, PECA, PBCA and PIBCA nanoparticles)
      were assayed for their toxicity on peritoneal resident and thioglycolate-elicited
      macrophages. Cellular viability was assessed by MTT tetrazolium salt assay,
      oxidative burst by NBT reduction and NO production by nitrite evaluation.
      RESULTS: The nanoparticles tested led to cellular morphological modifications and
      induced toxicity in both types of macrophages in culture. The
      polyalkylcyanoacrylate nanoparticles uptake by peritoneal macrophages caused an
      increase in respiratory burst, as assessed by the NBT reduction assay, and
      induced the release of soluble toxic factors to the culture medium. The
      association of LPS with the PMCA nanoparticles significantly stimulated the
      production of nitric oxide (NO) by resident macrophages. In contrast, the
      association of PBCA nanoparticles with LPS does not increase the nitrite
      production as compared with LPS alone, which may be due to a different physico
      chemical interaction between LPS and the two types of polymers. CONCLUSIONS: In
      cultured mice peritoneal macrophages, nanoparticles of PACA induce the production
      of oxygen reactive products, which cause changes in the cell metabolism of both
      resident and elicited macrophages. PMCA nanoparticles in association with LPS
      significantly increase the expression of the inducible isoform of nitric oxide
      synthase, leading to the release of large amount of NO, which may be highly
      cytotoxic to the cultured cells in the presence of peroxide generated from the
      oxidative burst.

PMID- 9034226
TI  - Renal disposition of recombinant human interleukin-11 in the isolated perfused
      rat kidney.
AB  - PURPOSE: To clarify the mechanism of the renal clearance of recombinant human
      interleukin- 11 (rhIL- 1), we investigated the renal disposition characteristics
      of rhIL-11 in the perfused rat kidney. METHODS: The disposition characteristics
      of (111)In-labeled rhIL-11 were analyzed using a single-pass indicator dilution
      technique and statistical moment analysis in the perfused rat kidney under
      filtering and nonfiltering conditions. RESULTS: Steady-state distribution volume
      (Vd) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3
      to 10 microg/kidney was between 0.35 and 0.40 ml/g kidney. However, Vd at the
      highest dose decreased to a value almost identical to that of bovine serum
      albumin, suggesting that there is a reversible and saturable interaction between
      the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable
      accumulation of rhIL-11 was observed while its urinary excretion was highly
      restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but
      still significant renal uptake. Taken together, the marked renal uptake of rhIL
      11 may be explained by both efficient tubular reabsorption and significant uptake
      from the capillary side. These processes were not saturable within the tested
      dose range. These characteristics of rhIL-11 are likely based on non-specific
      electrostatic interaction with the tissues due to its cationic charge in the
      cytokine. CONCLUSIONS: The renal disposition processes of rhIL-11 were clarified
      at organ level in a quantitative manner. These findings agree well with previous
      observations in an in vivo disposition study in mice.

PMID- 9034227
TI  - Prospective use of population pharmacokinetics/pharmacodynamics in the
      development of cisatracurium.
AB  - PURPOSE: The population PK/PD approach was prospectively used to determine the
      PK/PD of cisatracurium in various subgroups of healthy surgical patients.
      METHODS: Plasma concentration (Cp) and neuromuscular block data from 241 patients
      in 8 prospectively-designed Phase I-III trials were pooled and analyzed using
      NONMEM. The analyses included limited Cp-time data randomly collected from 186
      patients in efficacy/safety studies and full Cp-time data from 55 patients in
      pharmacokinetic studies. The effects of covariates on the PK/PD parameters of
      cisatracurium were evaluated. The time course of neuromuscular block was
      predicted for various patient subgroups. RESULTS: The population PK/PD model for
      cisatracurium revealed that anesthesia type, gender, age, creatinine clearance,
      and presence of obesity were associated with statistically significant (p < 0.01)
      effects on the PK/PD parameters of cisatracurium. These covariates were not
      associated with any clinically significant changes in the predicted recovery
      profile of cisatracurium. Slight differences in onset were predicted in patients
      with renal impairment and patients receiving inhalation anesthesia. Based on the
      validation procedure, the model appears to be accurate and precise. CONCLUSIONS:
      The prospective incorporation of a population PK/PD strategy into the clinical
      development of cisatracurium generated information which influenced product
      labeling and reduced the number of studies needed during development.

PMID- 9034228
TI  - Mirtazapine pharmacokinetics with two dosage regimens and two pharmaceutical
      formulations.
AB  - PURPOSE: To compare, in a clinical study of a special design, the pharmacokinetic
      profile of mirtazapine in 20 young healthy male volunteers on two treatment
      regimens with homothetic oral tablets at steady state: NOCTE (1 x 30 mg at 21.00
      h) and BID (15 mg at 21.00 h and 15 mg at 09.00 h). METHODS: Pharmacokinetic
      parameters were calculated from mirtazapine plasma levels assayed by gas
      chromatography with nitrogen-sensitive detection. A special analysis of variance
      allowed interesting interactions to be distinguished. RESULTS: The steady state
      was reached after 4 and 6 days for NOCTE and BID respectively; the difference was
      presumably due to intersubject variability. In accordance with pharmacokinetic
      theory, the peak-to-trough ratio at steady state was significantly lower
      (twofold) for BID than for NOCTE. Within BID, a small difference (approx. 10%)
      was found in the extent of absorption between evening and morning administration.
      Although statistically significant, this difference meets strict bioequivalence
      requirements. The regimens NOCTE and BID were found to be bioequivalent for the
      steady-state area-under-the-curve-curve and the peak time. Bioequivalence testing
      for the peak level was not meaningful due to the difference in dosing regimens.
      The observed elimination half-lives of 19.7 +/- 3.0 h and 20.8 +/- 2.7 h (n = 20)
      for NOCTE and BID, respectively are in agreement with previous results.
      CONCLUSIONS: Differences (if any) were found to meet strict bioequivalence
      requirements and were so small that they are of no clinical consequences.

PMID- 9034225
TI  - Intravenous infusion of RMP-7 increases ocular uptake of ganciclovir.
AB  - PURPOSE: The ability of intravenous (i.v.) infusions of the bradykinin agonist,
      RMP-7, to permeabilize the blood-ocular barriers (BOB) to the antiviral agent
      ganciclovir was investigated in guinea-pigs. METHODS: Different i.v. dosing
      regimens included pre-treatment with RMP-7 (0.2 microg/kg/min for 5 min) followed
      by either [3H]-ganciclovir (1 microCi/0.2 ml/min) alone, and/or co-infusion with
      RMP-7 and [3H]-ganciclovir. At specific times the animals were sacrificed, their
      eyes removed, and the retina and lens epithelium dissected and analyzed for the
      amount of radioactivity. RESULTS: Using the ratio of tissue vs. integrated plasma
      radioactivity concentration, a two-fold increase in ganciclovir steady-state
      levels were observed in the retina as well as lens epithelium following RMP-7
      pretreatment. Peak uptake effects were achieved with a 4.5 min ganciclovir
      infusion. Neither longer infusions of ganciclovir alone, nor co-infusions of RMP
      7 and ganciclovir further enhanced the uptake effects. Kinetic analysis indicated
      that RMP-7 increased the rate of ganciclovir entry (K(IN)) in studied ocular
      tissues, while the efflux of drug (K(OUT)) was not affected by this treatment.
      Finally, ganciclovir retina:plasma ratios elevated by RMP-7 pre-treatment,
      remained higher than control ratios within 60 min following cessation of 4.5 min
      ganciclovir infusion. CONCLUSIONS: These data offer further evidence that BOB and
      in particular the blood-retinal barrier can be permeabilized via bradykinin
      receptor stimulation. As the i.v. infusions of RMP-7 enhanced the retinal uptake
      of ganciclovir, it is suggested that a combination of RMP-7 and ganciclovir may
      provide a novel approach for treating cytomegalovirus retinis.

PMID- 9034229
TI  - The use of scintigraphy to provide "proof of concept" for novel polysaccharide
      preparations designed for colonic drug delivery.
AB  - PURPOSE: The aim of the present study was to provide "proof of concept" data in
      man for novel polysaccharide preparations designed for colonic drug delivery
      using gamma scintigraphy. METHODS: Two placebo calcium pectinate matrix tablet
      formulations were studied: one contained calcium pectinate and pectin (CaP/P) and
      was designed to rapidly disintegrate in the ascending colon, the other contained
      calcium pectinate and guar gum (CaP/GG) and was designed to disintegrate more
      slowly, releasing its contents throughout the ascending and transverse colon.
      Both formulations were enteric coated in order to protect them from the stomach.
      Ten healthy volunteers received either a CaP/P or CaP/GG tablet, in a randomised
      cross-over study. Transit and disintegration of the radiolabelled formulations
      was followed by gamma scintigraphy. Rat studies were conducted in order to verify
      that the expected colonic degradation of the polysaccharide formulations was as a
      consequence of bacterial enzyme attack. RESULTS: The in vivo clinical study
      confirmed the results obtained in the rat and bench in vitro fermentation models;
      complete tablet disintegration for Formulation CaP/GG appeared to be slower than
      that of Formulation CaP/P and the time and the location of complete tablet
      disintegration was more reproducible with Formulation CaP/P compared to
      Formulation CaP/GG. CONCLUSIONS: These results provide "proof of concept" data
      for the use of calcium pectinate preparations for drug delivery to the colon and
      highlight the value of scintigraphy in focusing the development strategy for
      colonic targeting preparations.

PMID- 9034230
TI  - Near-infrared spectroscopy as a nondestructive alternative to conventional tablet
      hardness testing.
AB  - PURPOSE: Near-infrared reflectance spectroscopy (NIRS) was used to evaluate and
      quantify the effect of compression force on the NIR spectra of tablets. METHODS:
      Flat, white tablets with no orientation (scoring, etc.) were manufactured on a
      Stokes Rotary Tablet Press. NIRS was used to predict tablet hardness on the
      following four formulations and one placebo matrix: hydrochlorothiazide (HCTZ)
      15% and 20% in a placebo matrix (microcrystalline cellulose and magnesium
      stearate), and chlorpheniramine maleate (CTM) 2% and 6% in a placebo matrix. Five
      or six levels of tablet hardness from 2 to 12 kg were used for each formulation.
      Laboratory hardness data was compared to NIR reflectance data using a NIRSystems
      Rapid Content Analyzer. Multiple linear regression and partial least squares
      regression techniques were used to determine the relationship between tablet
      hardness and NIRS spectra. RESULTS: An increase in tablet hardness produced an
      upward shift (increase in absorbance) in the NIRS spectra. A series of equations
      was developed by calibrating tablet hardness data against NIR reflectance
      response for each formulation. The results of NIRS hardness prediction were at
      least as precise as the laboratory hardness test (SE = 0.32). CONCLUSIONS: A NIRS
      method is presented which has the potential as an alternative to conventional
      hardness testing of tablets.

PMID- 9034231
TI  - Nebulization of NanoCrystals: production of a respirable solid-in-liquid-in-air
      colloidal dispersion.

PMID- 9034232
TI  - Antioxidant functions of inositol 1,2,3-trisphosphate and inositol 1,2,3,6
      tetrakisphosphate.
AB  - Iron chelates of inositol 1,2,3-trisphosphate and inositol 1,2,3,6
      tetrakisphosphate lacked free coordination sites and prevented the iron-catalyzed
      oxidation of ascorbic acid and peroxidation of arachidonic acid. In contrast,
      iron chelates of inositol 1,2,6-trisphosphate and inositol 1,2,5,6
      tetrakisphosphate contained available coordination sites, permitted iron
      catalyzed ascorbic acid oxidation, and enhanced arachidonic acid peroxidation. It
      was concluded that the 1,2,3-trisphosphate grouping of inositol hexakisphosphate
      was responsible for the inhibition of iron-catalyzed hydroxyl radical formation.
      The structure of the chelate with the phosphates in an axial-equatorial-axial
      configuration appeared to be the only possible inositol trisphosphate that could
      form bonds between six oxygen atoms and the six coordination sites on iron. Km
      values for cleavage by Escherichia coli alkaline phosphatase were as follows:
      inositol 1,2,3-trisphosphate, 56 microM; inositol 1,2,6-trisphosphate, 35 microM;
      inositol 1,2,3,6-tetrakisphosphate, 139 microM; and inositol 1,2,5,6
      tetrakisphosphate, 100 microM. The initial hydrolysis rates of 200 microM
      solutions of the latter three isomers by E. coli alkaline phosphatase were not
      affected by an equimolar concentration of iron, whereas the rate for inositol
      1,2,3-trisphosphate decreased in the presence of iron to 50% of the control.
      Therefore, the antioxidant potential of inositol 1,2,3-trisphosphate and inositol
      1,2,3,6-tetrakisphosphate in cells and other biological systems may be fortified
      by the resistance of their iron chelates to enzymatic hydrolysis of the
      functional 1,2,3-trisphosphate array.

PMID- 9034233
TI  - Free radical enhancement promotes leucocyte recruitment through a PAF and LTB4
      dependent mechanism.
AB  - In the present investigation we studied the concerted role of superoxide anion,
      platelet activating factor (PAF) and leukotriene B4 (LTB4) in the mechanism that
      results in polymorphonuclear leucocyte accumulation induced by oxygen free
      radicals in rat pancreas. This was done by comparing the effects of a PAF
      antagonist (BN-52021), a LTB4 inhibitor (MK-886) and superoxide dismutase (SOD)
      in a experimental rat model of inflammation elicited by the oxygen free radicals
      induced via infusion of xanthine/xanthine oxidase. Also, the effect of
      independent LTB4 infusion has been studied. The results show that increases in
      polymorphonuclear cell infiltration (evaluated by tissue histology),
      myeloperoxidase and LTB4 levels induced in pancreas by infusion of
      xanthine/xanthine oxidase were abolished by the administration of either the PAF
      antagonist, the LTB4 inhibitor, or SOD. The fact that BN-52021 could prevent
      neutrophil recruitment and LTB4 synthesis suggests that PAF is a necessary step
      for subsequent LTB4 synthesis and polymorphonuclear leucocyte accumulation.

PMID- 9034234
TI  - Filamin redistribution in an endothelial cell reoxygenation injury model.
AB  - Ischemia-reperfusion injury increases vascular permeability in part by generating
      reactive oxygen species that disassemble the endothelial cell actin dense
      peripheral band. This is followed by an increase in the number and diameter of
      intercellular gaps. Millimolar concentrations of reactive oxygen metabolites lead
      to nonspecific endothelial cell injury, but micromolar concentrations activate
      inflammatory second messenger cascades which produce distributional changes in
      endothelial cell cytoskeletal proteins. H2O2 (100 microM) causes translocation of
      filamin, from the membrane to the cytosol within 1 min. Subsequently, gap
      formation occurs within 10-25 min, which is attributed to rearrangement of the
      dense peripheral band of F-actin. Plasma membrane blebbing occurs after 90 min
      and decreases in mitochondrial activity occur after 1-2 h. Deferoxamine (iron
      chelator) and TEMPO (nonspecific free radical scavenger) inhibit these changes.
      H2O2 (100-1000 microM) does not increase endothelial cell intracellular Ca2+
      through 30 min and pretreating cells with a Ca2+-calmodulin kinase inhibitor or
      an intracellular Ca2+ chelator does not prevent filamin translocation. Filamin
      redistribution and actin rearrangement are early events in H2O2-mediated
      endothelial cell injury that appear to occur through Ca2+-independent pathways.

PMID- 9034235
TI  - Electron paramagnetic resonance studies on nitroxide radical 2,2,5,5-tetramethyl
      4-piperidin-1-oxyl (TEMPO) redox reactions in human skin.
AB  - Electron paramagnetic resonance (EPR) is currently being explored for the study
      of living biological systems. Among biophysical and biochemical applications, the
      study of nitroxide radical interactions with tissue antioxidants and oxidants is
      of growing interest. Skin is a target organ of the EPR methodology and is
      frequently exposed to oxidative stress. We investigated the piperidine-type
      nitroxide 2,2,5,5-tetramethyl-4-piperidin-1-oxyl (TEMPO) because it is skin
      permeable and readily accepts electrons in biological systems. TEMPO is readily
      scavenged on the surface of cultured human skin. Pretreatment of skin cultures
      with butylhydroperoxide, which decreases intracellular ascorbate and glutathione,
      causes inhibition of nitroxide scavenging. Exposure of skin cultures to
      dehydroascorbate, which is internalized and converted to ascorbate, leads to
      stimulation of nitroxide scavenging. In human keratinocytes and fibroblasts, the
      TEMPO radical is reversibly reduced to the hydroxylamine depending on the oxygen
      concentration and the availability of intracellular glutathione and ascorbate.
      Cell exposure to the glutathione synthetase inhibitor buthionine-sulfoximine
      depleted intracellular glutathione and inhibited nitroxide reduction; exposure to
      dehydroascorbate or glutathione-monoethylester increased intracellular ascorbate
      or glutathione concentration and stimulated nitroxide reduction. Quantitative
      considerations indicate that the major reduction site of TEMPO in skin and skin
      cells is the cytosol ascorbate/glutathione redox cycle. We suggest that analysis
      of TEMPO radical scavenging by the EPR technique is a convenient method for
      measuring skin ascorbate and thiol-dependent antioxidant activity in vitro and in
      vivo.

PMID- 9034236
TI  - Effect of a water-soluble vitamin E analog, trolox C, on retinal vascular
      development in an animal model of retinopathy of prematurity.
AB  - The debate over the efficacy of vitamin E as a therapy for retinopathy of
      prematurity (ROP) continues 45 years after it was first proposed. The
      discrepancies between one clinical study and another may be due to the difficulty
      of delivering a lipid-soluble molecule like vitamin E to the immature retina.
      Trolox C is a water-soluble analog of vitamin E with potent antioxidant activity.
      We have studied the effectiveness of intraperitoneal injection of Trolox C in an
      animal model of ROP. Albino rats were placed in 80% oxygen at birth where they
      remained for 14 d before sacrifice and assessment of retinal vasculature. Rats
      were administered 625 microg/kg Trolox C, or vehicle, by intraperitoneal
      injection on alternate days for the duration of the exposure. Other rats were
      simultaneously raised in room air, injected, and assessed as controls. Percent
      avascular retinal area, vascular leakage, and retinal capillary density were
      measured by computer-assisted image analysis. Trolox C-injected rats had
      significantly smaller avascular areas (14.6 +/- 4.8% vs. 25.4 +/- 6.3%), less
      leak area (0.04 +/- 0.07 mm2 vs. 0.16 +/- 0.14 mm2), and greater capillary
      density (24.3 +/- 2.6 pixel % vs. 18.9 +/- 3.1 pixel %) than vehicle-injected
      counterparts. These findings indicate that Trolox C facilitated the process of
      retinal vasculogenesis under hyperoxemic conditions. They also suggest that
      oxygen free radical-mediated damage plays a role in the pathologic effect of high
      oxygen rearing of newborn rats. Additional studies are warranted to determine
      precise site(s) and mechanism(s) of Trolox C activity in this and similar disease
      models in which peroxidation is believed to play a causal role.

PMID- 9034237
TI  - Antiinflammatory activity of tissue plasminogen activator in the carrageenan rat
      footpad model.
AB  - Exogenous plasminogen activators (PAs), such as streptokinase (SK) and tissue
      plasminogen activator (tPA), have been shown to significantly improve the
      mortality of patients with acute myocardial infarction. However, reperfusion of
      the myocardium is associated with neutrophil activation and infiltration into the
      infarct region. Plasminogen activators influence neutrophil function in vitro,
      but no data exists regarding the effect of exogenous PAs on inflammation in vivo.
      Therefore, we evaluated the effect of PAs on inflammation using the carrageenan
      induced rat footpad inflammation model. The magnitude of carrageenan-induced
      inflammation was determined by water-displacement and neutrophil infiltration,
      following administration of either tPA or SK to Sprague-Dawley rats. tPA (12
      mg/kg) inhibited carrageenan-induced inflammation (p < .01). In contrast,
      administration of SK (40,000 U/kg) enhanced inflammation. These results suggest
      that exogenous PAs influence the inflammatory process but specific PAs differ in
      their actions. Ultimately, these differences may influence the efficacy of these
      agents in the management of acute myocardial infarction and lead to further
      evaluation of tPA in other inflammatory diseases such as acute respiratory
      distress syndrome (ARDS) and rheumatoid arthritis (RA), in which neutrophil
      mediated injury is likely.

PMID- 9034238
TI  - Aminobenzoic acid compounds as HOCl traps for activated neutrophils.
AB  - This study was designed to develop traps for hypochlorous acid (HOCl) which could
      be used to detect HOCl in the microenvironment of activated neutrophils. Reagent
      HOCl was found to react with para-aminobenzoic acid (PABA) in aqueous solution to
      produce a predominant metabolite detectable by high performance liquid
      chromatography (HPLC). Mass spectroscopy and nuclear magnetic resonance
      identified this metabolite as the ring addition product 3-chloro PABA. The
      related compound para-aminosalicylic acid (PAS) was also metabolized by HOCl to 3
      chloro PAS. The formation of the 3-chloro metabolite was specific for reactions
      involving HOCl, since several other oxidants in chloride buffer failed to produce
      the metabolite. Human blood neutrophils activated by phorbol myristate acetate or
      zymosan in the presence of PABA (or PAS) used their HOCl to produce large amounts
      of the 3-chloro metabolite. The formation of 3-chloro PABA was inhibited by
      azide, catalase, and taurine, which is consistent with the production of the
      metabolite by the neutrophil myeloperoxidase (MPO) pathway. The reaction of HOCl
      with PABA and PAS was relatively slow as shown by competitive reactions with
      endogenous antioxidants like taurine, methionine, and glutathione. This was
      confirmed in reactions involving PABA/PAS and reagent HOCl or HOCl generated by
      the MPO enzyme system. In these in vitro systems, glutathione and serum
      completely inhibited the formation of the 3-chloro metabolite. In contrast,
      activated neutrophils metabolized PABA/PAS to the 3-chloro metabolite even in the
      presence of 1% serum. These findings demonstrate that PABA and PAS are specific
      trapping agents for HOCl produced by neutrophils in complex biological
      conditions.

PMID- 9034239
TI  - Oxygen free radicals and platelet activation.
AB  - This article reviews our current understanding of the role of oxygen free
      radicals in platelet activation. Several studies have indicated that platelets,
      in analogy to other circulating blood cells, are able to produce oxygen free
      radicals, which are likely to play an important role in the mechanism of platelet
      activation and aggregation. Platelet activation has been obtained with very low,
      physiologically relevant concentrations of radicals generated chemically, by
      leukocytes, and by hemoglobin derived from membrane leakage of erythrocytes.
      Knowledge of the role of reactive species in platelet physiology is relevant
      because platelets are brought into close contact with other cells capable of
      producing free radicals, such as neutrophils, macrophages, and endothelial cells,
      during the formation of thrombus. The physiopatological importance of these
      findings is high because it is now emerging that free radicals may have a role in
      the mechanism of atherosclerosis and its thrombotic complications, where the
      causative role of platelets is well documented. This background suggests
      therapeutic interventions with antioxidants as antiplatelet agents to improve the
      pharmacological effect of classical antiplatelet drug such as aspirin.

PMID- 9034240
TI  - TGF-beta1 triggers oxidative modifications and enhances apoptosis in HIT cells
      through accumulation of reactive oxygen species by suppression of catalase and
      glutathione peroxidase.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional polypeptide
      that is related to the progression of chronic pancreatitis. However, the
      mechanism of beta-cell damage by TGF-beta1 is unknown. Treatment with TGF-beta1
      enhanced internucleosomal DNA cleavage caused by exogenous hydrogen peroxide in a
      hamster pancreatic beta-cell line (HIT). TGF-beta1 also induced protein
      oxidation, assessed by measuring carbonyl groups in proteins, and was involved in
      reactions that lead to lipid peroxidation. This eventually destructs membrane
      lipids and forms malondialdehyde. We have investigated its effects on two major
      antioxidative enzymes, catalase and glutathione peroxidase (GPx). TGF-beta1
      suppressed mRNA expression as well as reduced the activities of catalase and GPx.
      The decrease in the catalase and GPx activities in TGF-beta1-treated cells
      resulted in an increase in intracellular peroxides as judged by flow cytometric
      analysis using a peroxide-sensitive dye, 2',7'-dichlorofluorescin diacetate.
      These data suggest that the augmented production of reactive oxygen species by
      TGF-beta1 through suppression of antioxidative enzymes may cause cellular damage
      and consequent apoptosis and induce pancreatitis or diabetes.

PMID- 9034241
TI  - Induction of a wide range of C(2-12) aldehydes and C(7-12) acyloins in the kidney
      of Wistar rats after treatment with a renal carcinogen, ferric nitrilotriacetate.
AB  - An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal
      tubular necrosis associated with lipid peroxidation and oxidative DNA damage that
      finally leads to a high incidence of renal cell carcinoma in rodents. In the
      present study, we investigated what kinds of C(2-12) saturated and unsaturated
      aldehydes and C(7-12) acyloins, metabolites of saturated aldehydes, are produced
      in the kidney and liver within 24 h after single i.p. administration of 15 mg
      Fe/kg of Fe-NTA, or after repeated (1 or 3 wk) i.p. administration of 5-10 mg
      Fe/kg of Fe-NTA. Amounts of twenty one aldehydes and five acyloins were
      determined by capillary column gas chromatography-negative-ion chemical
      ionization mass spectrometry with ammonia as reagent gas. Most of the aldehydes
      and all the acyloins measured revealed a significant dose-dependent increase 1 to
      3 h after single administration in the kidney, among which 4-hydroxy-2-nonenal
      (HNE) showed the highest increase (27.3-fold) and malondialdehyde (MDA) was the
      most abundant aldehyde (2.40 nmol/100 mg wet tissue). In the liver, however, the
      increase in aldehydes and acyloins was less prominent. After repeated
      administration of Fe-NTA, only 9 aldehydes (ethanal; furfural; trans,trans-2,4
      heptadienal; nonanal; trans-2,cis-6-nonadienal; HNE; decanal; trans-4,cis-4
      decenal; MDA) and 4 acyloins (3-hydroxyheptan-2-one; 3-hydroxyoctan-2-one; 3
      hydroxynonan-2-one; 3-hydroxydodecan-2-one) showed a significant increase.
      Immunohistochemistry further demonstrated an increased amount of HNE-modified and
      MDA-modified proteins in the renal proximal tubules after repeated Fe-NTA
      administration. Some of the aldehydes measured such as HNE and MDA are reportedly
      cytotoxic, genotoxic and mutagenic. Accumulation of these aldehydes may play a
      role in this renal carcinogenesis model.

PMID- 9034242
TI  - Enhancement of NO production from resident peritoneal macrophages by in vitro
      gamma-irradiation and its relationship to reactive oxygen intermediates.
AB  - The functional changes in macrophages (Mphi) following exposure to a high dose (6
      Gy) of gamma-rays in vitro were investigated. Resident peritoneal Mphi obtained
      from C57BL/6 mice were irradiated with gamma-rays (137Cs, 0.3 Gy/min). High-dose
      irradiation enhanced nitric oxide (NO) production from Mphi treated with
      interferon-gamma and their cytotoxic activity. The enhancement of NO production
      by irradiation was attributed to high levels of expression of the inducible
      nitric oxide synthase. Furthermore, the participation of reactive oxygen
      intermediates in NO production was examined. Nitric oxide production was not
      enhanced by treatment with the membrane-oxidizing agent tert-butyl hydroperoxide
      or the hypoxanthine/xanthine oxidase superoxide (O2.-)-generating system. On the
      other hand, NO production was enhanced by treatment with a low dose of hydrogen
      peroxide (H2O2), which can diffuse passively through the cell membrane and can be
      converted into hydroxyl radicals (HO.) that cause DNA breaks. In addition,
      treatment with low-dose actinomycin D, which induces DNA strand breaks, enhanced
      NO production, but hydroxyurea, which stops DNA replication without DNA strand
      breaks, had no such effect. These findings suggest that DNA strand breaks caused
      by hydroxyl radicals formed inside the cells by gamma-irradiation, or strand
      breaks caused directly by radiation, plays an important role in the enhancement
      of NO production, but peroxidation of cell membranes has little effect.

PMID- 9034243
TI  - Oleic acid rich diet protects against the oxidative modification of high density
      lipoprotein.
AB  - Oxidative modifications of lipoproteins could contribute to the development of
      atherosclerosis, but the influence of dietary fats on high density lipoprotein
      (HDL) oxidative modification is unknown. This study was designed to determine
      whether a diet rich in oleic acid could modulate the oxidative modification of
      HDL3. Twenty two healthy men were randomly placed on a 32-wk crossover study of
      an oleic acid rich diet supplied by a variant of sunflower oil vs a linoleic acid
      rich diet provided by conventional sunflower oil. Plasma HDL3 obtained after the
      diet rich in oleic acid showed a significantly higher oleic acid content in the
      phospholipid than lipoprotein isolated after the linoleic acid rich diet. HDL3
      isolated after the oleic acid rich diet had lower values of thiobarbituric acid
      reactive substances (TBARS) than HDL3 obtained after the linoleic acid rich diet
      both for native (mean +/- SE; 0.24 +/- 0.02 vs 0.42 +/- 0.08 nmol MDA/mg protein;
      p < 0.01) and copper oxidized HDL3 (0.75 +/- 0.06 vs 0.95 +/- 0.07 nmol MDA/mg
      protein; p < 0.01). Indeed, TBARS for native HDL3 were negatively correlated with
      the oleic acid to linoleic acid ratio and positively with the percentage of
      linoleic acid in their phospholipids. Interestingly, HDL3 after both diets had
      similar antioxidant vitamins A and E content. HDL3 overall composition and
      fluidity were similar after the two diets. Moreover, HDL3 obtained after both
      diets produced identical [3H] free cholesterol efflux from human monocyte-derived
      macrophages (29%) and fibroblasts (26%). In conclusion, HDL3 rich in oleic acid
      was less easily oxidized regardless of the content of antioxidants such as
      vitamins A and E. Therefore, dietary monounsaturated fatty acid prevent the
      oxidative modification of lipoproteins.

PMID- 9034244
TI  - Evolutionary significance of vitamin C biosynthesis in terrestrial vertebrates.
AB  - Evolution of vertebrates from aquatic medium to the terrestrial atmosphere
      containing high concentration of environmental oxygen was accompanied by tissue
      specific expression of the gene for L-gulonolactone oxidase (LGO). LGO is the
      terminal enzyme in the pathway of biosynthesis of ascorbic acid in animals. In
      this paper we present data to indicate that emergence of LGO is apparently to
      provide the terrestrial vertebrates with adequate amount of ascorbic acid and
      thereby protect their tissues against oxygen toxicity. Superoxide dismutase (SOD)
      was not induced in the early tetrapods. However, SOD activity has increased in
      the mammals which is accompanied by a decrease in the LGO activity. In fact,
      there has been an inverse relationship between LGO and SOD in the progress of
      evolution. SOD activity is markedly high in the guinea pig, flying mammal, monkey
      and man, the species those lack LGO. The inverse relationship between LGO and SOD
      is also observed in rats during postnatal development, that is when the new born
      rats are exposed to high concentration of atmospheric oxygen. Recent results from
      our laboratory indicate that ascorbic acid is specifically needed for protection
      of microsomal membranes against cytochrome P450-mediated lipid peroxidation and
      protein oxidation, where SOD is ineffective. Data presented in this paper also
      indicate an apparent tissue-specific correlation among LGO activity, P450 level
      and O2.- production during phylogenetic evolution.

PMID- 9034245
TI  - Peroxynitrite-induced tyrosine nitration and phosphorylation in human platelets.
AB  - Peroxynitrite (ONOO-) induces nitration of tyrosine residues and inhibits
      tyrosine phosphorylation in cell free systems. We investigated the effect of
      peroxynitrite on protein tyrosine nitration and phosphorylation in resting or
      thrombin-activated platelets. Peroxynitrite (150 microM) rapidly induced tyrosine
      nitration of 187, 164, 113, 89, and 61 kDa proteins in gel-filtered platelets
      which persisted up to 4.5 h. Repeated exposure of platelets to peroxynitrite
      produced increasing levels of nitration. Peroxynitrite also rapidly increased
      tyrosine phosphorylation of 120, 117, 95, 80-85, and 70 kDa platelet proteins,
      but this decreased by 5 min. The same pattern of tyrosine phosphorylation, but
      with higher intensity, was induced by thrombin in control platelets. Pretreatment
      of platelets with peroxynitrite decreased thrombin-induced tyrosine
      phosphorylation at 0.05 and 1 U/ml thrombin but not at 2 U/ml thrombin. Platelet
      activation responses such as P-selectin expression, serotonin secretion, and
      aggregation were also decreased by peroxynitrite treatment at low thrombin
      concentrations. Peroxynitrite exposure and tyrosine nitration decreased platelet
      sensitivity to thrombin but did not absolutely prevent tyrosine phosphorylation
      and other platelet responses.

PMID- 9034246
TI  - Antioxidant and prooxidant role of beta-carotene in murine normal and tumor
      thymocytes: effects of oxygen partial pressure.
AB  - The effects of the partial pressure of oxygen (pO2) on antioxidant efficiency of
      beta-carotene in inhibiting radical-initiated lipid peroxidation were studied in
      murine normal and tumor thymocytes. At 150 mm Hg pO2 (the pressure of oxygen in
      normal air), beta-carotene acted as an antioxidant, inhibiting radical-induced
      lipid peroxidation in both normal and tumor thymocytes. At 760 mm Hg p02, beta
      carotene lost its antioxidant activity in normal thymocytes and exhibited a dose
      dependent prooxidant effect in tumor thymocytes. In these cells, the prooxidant
      effect of beta-carotene was also accompanied by an increase of endogenous alpha
      tocopherol loss. beta-Carotene radical-trapping and autooxidation reactions were
      faster at 760 mm Hg pO2 than at 150 mm Hg pO2 in both normal and tumor thymocytes
      and the carotenoid was more rapidly consumed in tumor cells. These data point out
      a key role of the oxygen tension on the antioxidant effectiveness of beta
      carotene. They also show a selective prooxidant effect of beta-carotene under
      100% oxygen in tumor cells.

PMID- 9034247
TI  - The toxicities of native and modified hemoglobins.
AB  - Recent research on the potential use of hemoglobin derivatives as a blood
      substitute has revealed that the administration of large quantities of free
      hemoglobin into the circulation results in a variety of toxic side effects.
      Because it has been well established that hemoglobin, like myoglobin, has
      considerable pro-oxidant activity, a number of studies have appeared suggesting
      that the administered hemoglobins may catalyze various oxidative and peroxidative
      reactions, which in turn, would cause the observed pathologic conditions. This
      occurs as a result of the in vivo formation of highly oxidized forms of the
      native and modified hemoglobins. In addition, it has been proposed that
      considerable amounts of free hemin and iron may be generated as a result of the
      catabolism of the injected hemoglobin. Hemin is known to be very toxic when
      present in large amounts, and iron could catalyze the formation of hydroxyl
      radicals via Fenton-type reactions. Thus, the toxic activities of catabolic
      products of hemoglobin could also be involved in all or part of the observed side
      effects. The purpose of this review is to consider the conditions under which
      reactive species of hemoglobin may be formed in vivo, their potential reactivity,
      and whether their individual or combined oxidative activities could account for
      the biological damage that is observed in vivo following hemoglobin transfusions.

PMID- 9034248
TI  - Chemical and quantum mechanical studies of the free radical C-C bond formation in
      the lipoxygenase-catalyzed dimerisation of octodeca-9,12-diynoic acid.
AB  - Triple bond analogues of poly-unsaturated fatty acids are well-known inactivators
      of lipoxygenases. In an earlier study we proposed that, since 11-oxo-octadeca
      9,12-diynoic acid (11-oxo-ODYA) is the only oxygenated product formed during the
      irreversible inactivation of soybean lipoxygenase-1, the inactivation should
      proceed via a C11 centered octadeca-9,12-diynoic acid radical (ODYA radical). In
      the present study we investigated the lipoxygenase-catalysed formation of the
      ODYA radical. In the reaction of lipoxygenase with ODYA in the absence of
      dioxygen and in the presence of 13(S)-hydroperoxy-octadeca-9Z, 11E-dienoic acid
      (13-HPOD), free ODYA radicals were formed which resulted in the formation of
      three dimeric ODYA products in which one ODYA moiety is linked via its C9 (12%),
      C11 (72%) or C13 (16%) to the C11 methylene of the other ODYA moiety. With the ab
      initio Hartree-Fock method, using the 2,5-heptadiynyl radical as a model
      compound, the electron spin in the ODYA radical was calculated to be located for
      12.0, 75.0 and 12.0% on carbon atoms C9, C11 and C13 of the ODYA radical,
      respectively. The ODYA-ODYA dimer formation could thus be explained on the basis
      of the electron spin distribution in the ODYA radical. The dimer formation, i. e.
      reaction of an ODYA radical with an ODYA molecule was compared with the reaction
      of the ODYA radical with dioxygen. On the basis of this comparison it is
      concluded that a) the ODYA dimer formation occurs at the carbon atom with the
      highest electron spin population; b) ODYA dimer formation is predominantly a
      kinetically determined process; c) the electron spin distribution in the ODYA
      radical can be used to predict the composition of the dimer mixture; and d) the
      regiospecific oxygen addition in the formation of 11-oxo-ODYA is enzymatically
      controlled.

PMID- 9034249
TI  - High altitude training increases reactive carbonyl derivatives but not lipid
      peroxidation in skeletal muscle of rats.
AB  - The oxidative stress related consequences of physical training at high altitude
      are not known. The hypothesis was tested that physical training and exposure to
      high altitude have adverse effects on free radical generation and activities of
      antioxidant enzymes. The present results showed that 4 weeks of exercise at an
      altitude of 4000 m increased the activity of Mn-SOD in both white and red types
      of skeletal muscle. The activities of Cu,Zn-SOD, catalase, and glutathione
      peroxidase, as well as the level of lipid peroxidation measured by TBARS and
      lipid hydroperoxides, did not change significantly. In contrast, the level of
      reactive carbonyl derivatives measured by anti-2,4-dinitrophenylhydrazone
      antibodies and spectrophotometry showed an increase in both types of muscle of
      altitude trained rats compared with sea level trained and control groups. It was
      suggested that the oxidative modification of certain amino acids is due to the
      increasing gap between activity of SOD and peroxide scavenging enzymes, which
      results in increases in the number of hydrogen peroxide molecules. Thus, since
      the mechanism of generation and/or the mode of action of radicals resulting in
      lipid peroxidation and protein oxidation appears to be different in vivo, both
      processes should be studied during oxidative stress.

PMID- 9034250
TI  - Redox regulation of NF-kappa B activation.
AB  - Cytosolic reactions of the nuclear factor kappa B/inhibitor (NF-kappaB/IkappaB)
      complex leading to its activation, NF-kappaB translocation into the nucleus, DNA
      binding, and transactivation have been described with some degree of clarity, but
      the upstream processes that stimulate those cytosolic reactions remain obscure.
      These processes definitely involve multiple protein serine/threonine kinases, as
      proximal modifiers of IkappaB, as well as the corresponding phosphatases,
      upstream kinases, and phosphatases, including those acting on tyrosine residues.
      This complex cascade of phosphorylation and dephosphorylation is modulated by
      redox reactions of unknown nature in the sense that the oxidant status of the
      cytosol increases the phosphorylation and degradation of IkappaB. NF-kappaB
      action, however, requires a thioredoxin-dependent reduced status in the nucleus.
      Upstream kinase(s) and or phosphatase(s) prone to thiolation or oxidation of
      vicinal SH groups are at present considered the best candidates mediating the
      redox regulation of NF-kappaB.

PMID- 9034251
TI  - Raising the standard of hemodynamic monitoring: targeting the practice or the
      practitioner?

PMID- 9034252
TI  - Beware of errors in blood glucose measurement.

PMID- 9034253
TI  - Intensive care physicians' insufficient knowledge of right-heart catheterization
      at the bedside: time to act?
AB  - OBJECTIVE: To evaluate French, Swiss, and Belgian intensive care physicians'
      knowledge about the pulmonary artery catheter. DESIGN: Survey study by
      questionnaire. SETTING: Eighty-six European university and nonuniversity
      intensive care units (ICUs). SUBJECTS: One hundred thirty-four ICUs identified
      from the directories of two European intensive care medicine societies were asked
      to participate. Five hundred thirty-five critical care physicians working in 86
      ICUs participated. INTERVENTIONS: In any particular ICU, all physicians were to
      complete--simultaneously, anonymously and without prior notice--a multiple choice
      questionnaire consisting of 31 questions regarding all aspects of bedside
      pulmonary artery catheterization. This questionnaire was the same one already
      used and extensively validated in a similar study conducted several years earlier
      in the United States and Canada. MEASUREMENTS AND MAIN RESULTS: The percentage of
      correct answers per participant (score) was tabulated. Sixty-eight percent of
      respondents still in training (n = 232) believed that their knowledge of the
      pulmonary artery catheter was less than adequate; 36% of those who had completed
      their postgraduate training (n = 294) also believed their knowledge to be
      inadequate. The mean score of all respondents was 72.2 +/- 14.4%, significantly
      lower (p <.0001) in case of uncompleted postgraduate training (67.3 +/- 14.7%,
      lower quartile 56.7%, median 70.0%, upper quartile 76.7%), as compared with
      completed postgraduate training (76.1 +/- 13.0%, lower quartile 70.0%, median
      80.0%, upper quartile 86.7%). When using multivariate analysis, the location of
      the ICU in a university hospital, the belief of respondent that his/her knowledge
      of the pulmonary artery catheter was adequate, and the responsibility for
      supervising catheter insertion were the only independent predictors of good
      performance on the questionnaire (p < .001 for all three variables). It was
      impossible to identify any subcategory of physicians with a uniformly good
      knowledge of the pulmonary artery catheter. The proportion of incorrect answers
      to some basic items was disturbingly high. For instance, approximately 50% of the
      respondents, whether trained or in training, did not correctly identify pulmonary
      artery occlusion pressure from a clear chart recording. CONCLUSIONS: Knowledge of
      right-heart pulmonary artery catheterization is not uniformly good among ICU
      physicians. Accreditation policies and teaching practices concerning this
      technique need urgent revision.

PMID- 9034254
TI  - Platelet-activating factor antagonism improves ventricular contractility in
      endotoxemia.
AB  - OBJECTIVES: Endotoxin stimulates platelet-activating factor production and also
      causes a decrease in myocardial contractility within a few hours in animal models
      of sepsis. Platelet-activating factor by itself decreases left ventricular
      contractility. We investigated whether platelet-activating factor contributes
      substantially to the decrease in left ventricular contractility seen in sepsis.
      DESIGN: Prospective, randomized, controlled animal study. SETTING: University
      research laboratory. SUBJECTS: Twenty-two juvenile, cross-bred pigs.
      INTERVENTIONS: Anesthetized pigs were pretreated with a platelet-activating
      factor receptor antagonist (L-659,989) or vehicle (control), and then treated
      with endotoxin or saline (control). Hemodynamics and left ventricular pressures
      (Millar catheter) and volumes (conductance catheter) were measured. Left
      ventricular contractility was assessed using the slope, or maximum elastance
      (Emax), of the end-systolic pressure-volume relationship. MEASUREMENTS AND MAIN
      RESULTS: In the control/endotoxin group, 4 hrs after endotoxin administration,
      Emax had decreased by 41 +/- 4% (p < .05) and mean arterial pressure had
      decreased by 32 +/- 3% (p < .05). In the L-659,989/endotoxin group, the decreases
      in Emax (26 +/- 2%, p < .05) and mean arterial pressure (16 +/- 7%) were
      significantly attenuated compared with the control/endotoxin group (p < .05).
      CONCLUSIONS: We conclude that platelet-activating factor plays a modest but
      statistically significant role in the early decrease in left ventricular
      contractility after endotoxin administration. Inhibition of platelet-activating
      factor during sepsis might be beneficial for left ventricular mechanics and
      hemodynamics.

PMID- 9034255
TI  - Intratracheal pressure monitoring during synchronized intermittent mandatory
      ventilation and pressure controlled-inverse ratio ventilation.
AB  - OBJECTIVES: To directly measure airway pressures proximal and distal to
      endotracheal tubes during conventional synchronized intermittent mandatory
      ventilation (SIMV) and pressure controlled-inverse ratio ventilation (PC-IRV),
      and to compare them with these values measured by the ventilator. DESIGN:
      Prospective, nonrandomized study. SETTING: Surgical intensive care unit at a
      trauma center. PATIENTS: Group 1: Eight intubated adult patients connected to
      mechanical ventilators in the SIMV mode were studied. All patients required
      mechanical ventilation following traumatic injuries. Group 2: Five intubated
      adult patients with adult respiratory distress syndrome connected to mechanical
      ventilators were studied. INTERVENTIONS: A small polyethylene catheter was
      threaded through each endotracheal tube such that it could be positioned to
      measure pressures proximal and distal to the tubes. MEASUREMENTS AND MAIN
      RESULTS: During SIMV, a significant pressure gradient exists across endotracheal
      tubes. In addition, although initiation of PC-IRV did lead to a lower peak airway
      pressure measured proximally, intratracheal peak airway pressure was unchanged.
      CONCLUSIONS: A pressure gradient exists during inspiration from the ventilator to
      the trachea in mechanically ventilated patients. Tracheal pressures cannot be
      predicted from proximal airway pressure monitors because of marked variation in
      endotracheal tube resistance in vivo. Initiation of PC-IRV does not result in a
      decrease in peak airway pressure when measured intratracheally.

PMID- 9034256
TI  - Influence of blood sample oxygen tension on blood glucose concentration measured
      using an enzyme-electrode method.
AB  - OBJECTIVE: To determine the accuracy of a bedside glucometer with an enzyme
      electrode sensor based on enzyme oxidation by glucose oxidase. DESIGN:
      Prospective, cross-sectional clinical study. SETTING: Operating room in a public
      hospital. PATIENTS: Fifty-four patients undergoing surgical procedures for a
      derivation (n = 17) and a validation (n= 37) study. INTERVENTIONS: Arterial blood
      samples were obtained via a 20-gauge cannula inserted into each patient's radial
      artery. MEASUREMENTS AND MAIN RESULTS: Glucose measurements and arterial blood
      gas analyses were concurrently performed, using 48 blood samples for the
      derivation study and 45 blood samples for the validation study of this technique.
      Blood glucose concentrations were measured with both a bedside glucometer using
      an enzyme-electrode method and a laboratory glucometer based on the colorimetric
      method. The bedside glucometer consistently underestimated the glucose
      concentrations and the underestimation was related to the sample oxygen tension
      but not to hematocrit, plasma protein, creatinine, uric acid, or bilirubin. The
      present investigation used the following correction formula: (corrected glucose
      value) = (glucose concentration obtained by a bedside glucometer) + 0.1 x (sample
      oxygen tension) + 16. The corrected data were in agreement with the laboratory
      determined glucose values (i.e., the mean difference and precision were 0.4 and
      7.1 mg/dL, respectively). A validation study confirmed the generalization of the
      present correction formula which facilitates a more accurate estimation of blood
      glucose concentrations. CONCLUSIONS: Blood glucose values measured using a
      bedside glucometer in this study were influenced by the sample oxygen tension. We
      used a corrective equation which improved the accuracy of estimating blood
      glucose values to a clinically acceptable range.

PMID- 9034257
TI  - N-acetylcysteine improves indocyanine green extraction and oxygen transport
      during hepatic dysfunction.
AB  - OBJECTIVES: To investigate whether the beneficial systemic hemodynamic effects of
      N-acetylcysteine, an agent that increases cyclic guanosine monophosphate (cGMP)
      concentration in fulminant hepatic failure, are present in a range of liver
      disorders and what concurrent effect this agent has on the hepatic-splanchnic
      circulation. SETTING: Liver Failure Unit, King's College Hospital, London, UK.
      PATIENTS: Fifteen patients with hepatic dysfunction who were mechanically
      ventilated, either after liver transplantation or during an acute or
      decompensated chronic liver disorder. INTERVENTIONS: Prostacyclin was
      administered at a continuous infusion rate of 5 ng/kg/min for 60 mins. After a
      washout period, the hemodynamic effects of this infusion were compared with the
      effects present during infusion of N-acetylcysteine at 150 mg/kg in 250 mL of 5%
      dextrose in water over 15 mins and then 50 mg/kg in 250 mL of 5% dextrose for 45
      mins at an infusion rate of 62.5 mL/hr. MEASUREMENTS AND MAIN RESULTS: Following
      N-acetylcysteine infusion, the baseline oxygen delivery (DO2) increased from 667
      +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in
      13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (p< .01). Indocyanine
      green clearance, as determined by a fiberoptic physiologic monitoring system,
      also improved in 13 of 15 patients (7.3 +/- 4.2% to 11.8 +/- 4.0% [mean change
      100%, 95% confidence interval 9 to 256]) (p = .002). Patients who were defined as
      responders in relation to systemic hemodynamics (VO2 of >10% from baseline [n =
      6; 40%]) had a significantly lower baseline consumption compared with that of
      nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the
      increments in VO2 and indocyanine green clearance was observed (r2 = .21; p =
      .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not
      VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION: N
      acetylcysteine increases systemic VO2 in a proportion of patients with a wide
      variety of hepatic disorders. In addition, N-acetylcysteine elicits an
      improvement in indocyanine green clearance. These properties may be clinically
      useful in a range of critical illnesses where systemic or hepatic-splanchnic
      circulations are compromised.

PMID- 9034258
TI  - Effects of preoperative intentional hemodilution on the extravasation rate of
      albumin and fluid.
AB  - OBJECTIVE: To evaluate the effects of preoperative intentional hemodilution with
      4% albumin solution on the extravasation rate of intravascular albumin and fluid
      in surgical patients. DESIGN: A prospective, randomized, clinical study. SETTING:
      University teaching hospital. PATIENTS: Two groups (control group [group 1] and
      hemodiluted group [group 2]) of 13 healthy patients were studied during a long
      term (>4 hrs) surgical procedure. INTERVENTIONS: Autologous technetium-99m
      (99mTc)-labeled red blood cells and indium-oxine ((111)In)-labeled human serum
      albumin were injected intravenously during anesthesia at T = 0 min in the two
      groups for the determination of total blood volume and albumin diffusion space,
      respectively. In addition, body tetrapolar electrical impedance was used to
      assess extracellular fluid volume. In the hemodiluted group (group 2), 15 mL/kg
      of blood was withdrawn over 30 mins (T = 20 mins to T = 50 mins) and
      simultaneously replaced by an equal volume of 4% albumin solution (0.6 g/kg).
      MEASUREMENTS AND MAIN RESULTS: The albumin diffusion space, the colloid oncotic
      pressure, the plasma albumin concentration and the electrical impedance were
      measured before (T = 10 mins) and after (T = 60, 120, and 240 mins) hemodilution.
      Urine was collected from T = 10 mins to T = 240 mins. The total blood volume was
      calculated at T = 10 mins. No differences in the initial values were found
      between the two groups. In group 2, hemodilution (hematocrit 30 +/- 3%) resulted
      in a steeper increase in the albumin diffusion space (p < .05) and a progressive
      decrease in the body electrical impedance (p < .05). The extravasation rate of
      albumin was 0.052 +/- 0.007 mL/kg/min in group 2 vs. 0.038 +/- 0.020 mL/kg/min in
      group 1 (p < .05). The value of calculated plasma volume at T = 0 min did not
      shown any difference between the two groups. This value was then lower than
      expected in group 2, corresponding to a loss of plasma volume of >3 mL/kg. Urine
      output was significantly lower in group 2 than in group 1 (0.7 +/- 0.4 vs. 1.4 +/
      1.0 mL/min, respectively; p < .05). A comparable decrease in colloid oncotic
      pressure and in plasma albumin concentration was observed in both groups.
      CONCLUSIONS: These results suggest that preoperative hemodilution using 4%
      albumin on a 1:1 volume basis for blood substitution during a prolonged surgical
      procedure with reduced blood losses enhances the extravasation rate of albumin
      and fluid to the interstitial tissues, impeding the maintenance of isovolemia.
      These findings support the use of a volume of infused colloid solution higher
      than that of withdrawn blood during preoperative hemodilution.

PMID- 9034259
TI  - Randomized, double-blind study of intravenous human albumin in hypoalbuminemic
      patients receiving total parenteral nutrition.
AB  - OBJECTIVE: To determine whether replacement of human albumin will improve a
      patient's prognosis. DESIGN: A randomized, double-blind, controlled study in
      which 25 g of human albumin vs. placebo was administered intravenously daily.
      SETTING: A university-affiliated hospital. PATIENTS: Thirty-six patients with
      hypoalbuminemia (serum albumin of <2.5 g/dL), receiving total parenteral
      nutrition. None of the patients had known cancer, cirrhosis, or nephrotic
      syndrome. INTERVENTIONS: Each patient received at least 6 days of therapy (6 to
      24 days of albumin; 7 to 32 days of placebo). Four subjects were excluded from
      the study since they received therapy for <6 days. One patient was excluded from
      the study after nephrotic syndrome was identified. Albumin metabolic rates for
      those patients receiving albumin were estimated using the formula: Metabolism of
      albumin = 25 g/day + (albumin 1 - albumin 2)(Vd)/days, where albumin 1 and 2 are
      the serum albumin concentrations (g/L) at the beginning and end of the serum
      sampling intervals, respectively; Vd is the volume of distribution (L); and days
      relates to the number of days of the sampling interval. MEASUREMENTS AND MAIN
      RESULTS: Sixteen patients received albumin; 15 patients received placebo. One
      patient receiving placebo and two patients receiving albumin died within 30 days.
      One patient who received placebo and three patients who received albumin
      developed sepsis or bacteremia; four patients who received placebo and seven
      patients who received albumin developed pneumonia during the study (NS). The
      serum albumin increased in all patients receiving intravenous albumin, but one
      patient received intravenous albumin for only 6 days. The mean serum albumin
      concentration increased by 1.42 g/dL in the albumin patients, and increased by
      0.29 in the placebo patients (p < .0001 by unpaired t-test). Mean initial albumin
      metabolism was 17.4 g/day (0.3 g/kg/day). At the end of therapy, albumin
      metabolism was 20.5 g/day (0.36 g/kg/day) (paired t-test, p = .4, NS).
      CONCLUSIONS: a) The administration of intravenous albumin to hypoalbuminemic
      patients receiving total parenteral nutrition does not improve morbidity or
      mortality. b) Albumin metabolic rates, initially related to the catabolic state,
      are high; later, these rates are high related to filling of the albumin space and
      gluconeogenesis. c) On the basis of the high albumin catabolic rates at the end
      of the infusion, doses of albumin of <25 g/day might be sufficient to replace
      albumin stores.

PMID- 9034260
TI  - The unassisted respiratory rate/tidal volume ratio accurately predicts weaning
      outcome in postoperative patients.
AB  - OBJECTIVE: To evaluate the accuracies of the respiratory rate/tidal volume ratio
      (rate/volume ratio), minute volume, and negative inspired force in predicting
      weaning outcome in postoperative mechanically ventilated patients. DESIGN: A
      prospective, observational study. SETTING: Surgical intensive care unit of a 270
      bed community teaching hospital. PATIENTS: One hundred eighty-three
      postoperative, mechanically ventilated patients. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The spontaneous minute volume, unassisted
      respiratory rate/tidal volume ratio, and negative inspired force were measured
      just before weaning. The rate/volume ratio was remeasured after 30 to 60 mins of
      weaning. Weaning was conducted by the patients' primary physicians. Weaning
      success was defined as unassisted breathing for >24 hrs. Predictive
      characteristics were computed using threshold values of 100 breaths/min/L, 10
      L/min, and -20 cm H2O for the rate/volume ratios, minute volume, and negative
      inspired force, respectively. Receiver operating characteristic curves were also
      constructed to assess each parameter. Sensitivities for the initial rate/volume
      ratio, rate/volume ratio after 30 mins, minute volume, and negative inspired
      force were 0.97, 0.96, 0.76, and 0.96, respectively. Specificities were 0.33,
      0.31, 0.40, and 0.07, respectively. Areas (+/- SD) for receiver operating
      characteristic curves were 0.76 +/- 0.08, 0.75 +/- 0.06, 0.54 +/- 0.08, and 0.62
      +/- 0.07, respectively. The rate/volume ratio after 30 mins correlated with the
      initial rate/volume ratio; the rate/volume ratio after 30 mins did not add
      significant, additional predictive information. CONCLUSIONS: The rate/volume
      ratio measured at the beginning and after 30 mins of weaning is more highly
      predictive of weaning outcome than the negative inspired force and minute volume.
      The principal weakness of the rate/volume ratio is false-positive results.

PMID- 9034261
TI  - Spectral analysis of systemic arterial pressure and heart rate signals as a
      prognostic tool for the prediction of patient outcome in the intensive care unit.
AB  - OBJECTIVES: To evaluate the applicability of changes in spectra of systemic
      arterial pressure and heart rate signals in the prediction of patient outcome in
      an adult intensive care unit (ICU). To compare the prognostic predictability of
      this method with the Acute Physiology and Chronic Health Evaluation II (APACHE
      II) scoring system. DESIGN: Prospective data collection from 52 ICU patients.
      SETTING: Adult ICU at a large, university-affiliated, medical center. PATIENTS:
      Consecutive patients who were admitted to the adult ICU due to noncardiac
      emergencies, and who remained for at least 2 days. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The demographic data, diagnosis, and survival data
      were recorded for each patient enrolled in this study. For the period between
      admission and 24 hrs before discharge, the APACHE II score was tabulated daily.
      Likewise, continuous, on-line, and real-time spectral analysis of systemic
      arterial pressure and heart rate signals was carried out every day for at least
      30 mins at 2200 to 2400 hrs. The averaged power density values during this 30-min
      recording period of the high-frequency (0.15 to 0.4 Hz), low-frequency (0.08 to
      0.15 Hz), and very low-frequency (0.016 to 0.08 Hz) components of systemic
      arterial pressure and heart rate signals were subsequently computed. Systemic
      vascular resistance index and cardiac index were also determined daily. We
      observed a trend of changes in the spectral components of systemic arterial
      pressure and heart rate signals in patients who eventually survived (n = 25) or
      died (n = 27). Progressive increases in the power density values of both the low
      frequency and very low-frequency components of systemic arterial pressure and
      heart rate signals appeared to be related to recovery. Conversely, progressive
      decreases in the power density values of these spectral components was indicative
      of deterioration and fatality. The predicted outcome based on the trend of
      changes in the low-frequency and very low-frequency components of systemic
      arterial pressure and heart rate signals correlated positively with daily APACHE
      II scores. No direct correlation, however, was indicated by mean systemic
      arterial pressure, heart rate, systemic vascular resistance index, and cardiac
      index. We also confirmed that the differential trend of spectral changes in
      patients who survived or died was not due to circadian rhythm, nor alterations in
      the responsiveness of the blood vessels to intravenous infusion of dopamine.
      CONCLUSION: Power spectral analysis of systemic arterial pressure and heart rate
      signals offers a reasonable means of monitoring acute, critically ill patients,
      and may be used as an alternative prognostic tool for the prediction of patient
      outcome in the ICU.

PMID- 9034262
TI  - Unloadiing of the work of breathing by proportional assist ventilation in a lung
      model.
AB  - OBJECTIVES: Proportional assist ventilation is devised to increase airway
      pressure in proportion to inspiratory effort. A systematic study of the
      performance of this new mode of ventilation has not been presented. We tested in
      the laboratory the capability of proportional assist ventilation to unload the
      work of breathing in proportion to ventilatory drive, under a variety of
      mechanical loads. DESIGN: During variations of "ventilatory drive" (i.e., tidal
      volume), unloading of the work of breathing by proportional assist ventilation
      was contrasted with unloading by pressure-support ventilation. SETTING: The
      respiratory laboratory of a university-affiliated teaching hospital. SUBJECT: A
      bellows-in-a-box lung model, powered by a sine wave air flow generator.
      INTERVENTIONS: Proportional assist and pressure-support ventilation were preset
      to provide comparable support at a baseline "ventilatory drive" of 0.7-L tidal
      volume. The set levels of proportional assist and pressure-support ventilation
      were subsequently applied to five tidal volumes, from 0.2 to 1.2 L. Three levels
      of inspiratory support and three settings of mechanical load were evaluated.
      MEASUREMENTS AND MAIN RESULTS: Proportional assist ventilation significantly (p <
      .05) reduced the work of breathing of the lung model at all but the lowest tidal
      volume (0.2 L). The preset proportion of ventilatory support (30%, 50%, and 70%)
      unloaded the work of breathing uniformly as ventilatory drive was varied at tidal
      volumes of > or = 0.5 L, but not always at tidal volumes of < or = 0.4 L. In
      contrast, pressure-support ventilation overassisted low tidal volumes and
      underassisted high tidal volumes (p < .05). CONCLUSIONS: In a lung model, a
      prototype system delivering proportional assist ventilation provided uniform
      unloading of the work of breathing as the ventilatory drive was varied within a
      tidal volume range of 0.5 to 1.2 L. These findings confirm the theoretical
      modeling of proportional assist ventilation. This system, however, failed to
      properly unload low tidal volumes of 0.2 to 0.4 L.

PMID- 9034263
TI  - Gentamicin pharmacokinetics in neonates with patent ductus arteriosus.
AB  - OBJECTIVES: To determine the effect of patent ductus arteriosus on the
      pharmacokinetics of gentamicin in neonates and to examine whether any particular
      pharmacokinetic parameter is of value as a marker of patent ductus arteriosus.
      DESIGN: Cohort study of neonates treated with gentamicin, according to a standard
      dosing protocol. SETTING: A 24-bed, Level III, neonatal intensive care unit.
      PATIENTS: Neonates treated with gentamicin at the time of admission to the
      neonatal intensive care unit, using a standard protocol, and who were < 36 wks of
      gestational age. INTERVENTIONS: All patients received a gentamicin loading dose,
      and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in
      order to determine pharmacokinetic parameters and calculate the optimum
      maintenance dose. Those neonates subsequently diagnosed to have patent ductus
      arteriosus, based on clinical suspicion and echocardiographic confirmation, were
      compared with those neonates without clinically suspected patent ductus
      arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one
      compartment model. MEASUREMENTS AND MAIN RESULTS: A total of 322 courses of
      gentamicin were administered (patent ductus arteriosus, n = 106; control, n =
      216). Gentamicin clearance was decreased in the patent ductus arteriosus group
      vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of
      distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than
      for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful
      marker for presence of patent ductus arteriosus, with a 92% specificity for
      patent ductus arteriosus. CONCLUSIONS: Gentamicin dosing should be altered in
      neonates with patent ductus arteriosus to reflect the impact of higher volume of
      distribution and lower clearance. When the gentamicin volume of distribution
      exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus
      arteriosus.

PMID- 9034264
TI  - Reduced airway resistance and work of breathing during mechanical ventilation
      with an ultra-thin, two-stage polyurethane endotracheal tube (the Kolobow tube).
AB  - OBJECTIVES: To compare dynamic pulmonary function studies using the ultrathin
      walled Kolobow endotracheal tube, with conventional endotracheal tubes of similar
      external diameter on rabbits during mechanical ventilation. To test the
      hypothesis that the increased internal diameter of the Kolobow tube will result
      in decreased airway resistance and work of breathing. DESIGN: Controlled animal
      study. SETTING: Institutional animal research facility. SUBJECTS: Adult female
      Dutch Belted rabbits (n = 6), weighing 1.4 to 1.6 kg. INTERVENTIONS: The animals
      were initially intubated with a conventional endotracheal tube (2.5-mm internal
      diameter; 3.6-mm outer diameter); they were paralyzed and placed on a mechanical
      ventilator. Ventilatory settings were adjusted to obtain standard arterial blood
      gases: pH of 7.35 to 7.45; PaCO2 of 35 to 40 torr (4.7 to 5.3 kPa), and PaO2 of
      90 to 100 torr (12.0 to 13.3 kPa). After the stabilization period, pulmonary
      function tests (PFTs) were measured (period 1), the conventional endotracheal
      tube was replaced with a Kolobow tube, and PFTs were measured again and recorded
      (period 2). While continuously monitoring tidal volume, the peak inspiratory
      pressure was decreased to match the tidal volume measured during ventilation with
      the conventional endotracheal tube. Once the desired tidal volume was reached,
      PFTs were recorded (period 3). Flows were unchanged during the experiment and the
      length of the endotracheal tubes was the same for both the conventional and the
      Kolobow tube. MEASUREMENTS AND MAIN RESULTS: Mean values of the airway resistance
      and work of breathing from periods 1 and 3 were compared using the Student's t
      test. There was a 59% decrease in total airway resistance (p = .001) and 45%
      decrease in the work of breathing (p = .0006). CONCLUSIONS: The use of the
      ultrathin walled Kolobow endotracheal tube resulted in significant decreases in
      airway resistance and work of breathing, which has the potential for improving
      the ventilatory mechanics in very small premature newborns.

PMID- 9034265
TI  - Differential effects of nitric oxide synthase modulation on porcine systemic and
      pulmonary circulation in vivo.
AB  - OBJECTIVE: To study and compare the effects of inhibiting endothelial nitric
      oxide synthase on systemic and pulmonary circulation in an in vivo model. DESIGN:
      Prospective, randomized, controlled study. SETTING: Laboratory for experimental
      surgery at a university medical center. SUBJECTS: Seventeen anesthetized,
      mechanically ventilated pigs. INTERVENTIONS: To produce a stable and continuous
      stimulation of endothelial nitric oxide synthase, an infusion of acetylcholine
      was given to one group of animals (n = 5) in a dose that decreased mean arterial
      pressure by 15%. After 45 mins, N(G)-monomethyl-L-arginine (L-NMMA) was given in
      a dose of 3 mg/kg for 5 mins in order to inhibit the enzyme. A second dose of 10
      mg/kg was given 30 mins later. L-arginine was then given in a dose of 100 mg/kg
      to reverse the inhibition. One group of animals (n = 6) received a single dose of
      indomethacin (2.5 mg/kg) 15 mins after the start of acetylcholine infusion. L
      NMMA and L-arginine were then given. In a control group (n = 5), the effects of L
      NMMA and L-arginine were studied without acetylcholine. Circulatory parameters
      were monitored and resistance indices were calculated via arterial, central
      venous, and pulmonary artery catheters. MEASUREMENTS AND MAIN RESULTS: In control
      animals, 3 and 10 mg/kg of L-NMMA induced an increase in mean arterial pressure
      of 14% and 25%, respectively, with similar increases in systemic vascular
      resistance. Mean pulmonary arterial pressure increased by 22% and 48%,
      respectively. Acetylcholine lowered mean arterial pressure by 15% and did not
      affect the relative changes induced by L-NMMA. Acetylcholine had no effect on
      pulmonary resting tone but enhanced the pulmonary hypertension and increase in
      resistance induced by L-NMMA. This enhancement was abolished by indomethacin,
      which produced systemic hypertension while no effect on pulmonary pressure was
      seen. CONCLUSIONS: A basal release of nitric oxide contributes to the maintenance
      of normal vascular tone in the anesthetized pig. Stimulation of endothelial
      nitric oxide synthase by acetylcholine did not result in any further pulmonary
      vasodilation as was seen in the systemic circulation. Inhibition of nitric oxide
      synthase had a greater effect on pulmonary pressure than on systemic pressure.
      However, this difference was abolished by the administration of indomethacin.
      Increased nitric oxide release or acetylcholine itself seems to stimulate the
      production of a vasoconstricting prostanoid in the pulmonary circulation.

PMID- 9034266
TI  - Role of superoxide and nitric oxide in platelet-activating factor-induced acute
      lung injury, hypotension, and mortality in rats.
AB  - OBJECTIVE: To investigate the role of superoxide and nitric oxide in platelet
      activating factor-induced acute lung injury, hypotension, and mortality. DESIGN:
      Prospective, randomized, controlled, experimental study. SETTING: University
      research laboratory. SUBJECTS: Anesthetized male Wistar rats (180 to 220 g) were
      studied. INTERVENTIONS: In the first set of experiments, animals were divided
      into three groups. Group 1 received platelet-activating factor (2 microg/kg
      i.v.). Group 2 received recombinant human superoxide dismutase (50,000 U/kg i.v.)
      30 mins before platelet-activating factor injection. Group 3 received vehicle
      agents. In the second set of experiments, animals were divided into six groups
      that received N(G)-nitro-L-arginine (L-NNA), a selective inhibitor of nitric
      oxide synthesis, or L-arginine, the physiologic precursor of nitric oxide
      synthesis: a) vehicles (i.v.); b) vehicle plus L-arginine (100 mg/kg i.v.); c)
      vehicle plus L-NNA (10 mg/kg i.v.); d) vehicle plus platelet-activating factor (2
      microg/kg i.v.); e) L-arginine plus platelet-activating factor; and f) L-NNA plus
      platelet-activating factor. The first intravenous administration was given 5 mins
      before the second intravenous injection for each group. MEASUREMENTS AND MAIN
      RESULTS: In the first set of experiments, vascular labeling with Monastral blue B
      demonstrated diffuse microvascular injury in the alveolar capillary beds 2 hrs
      after platelet-activating factor challenge. Thiobarbituric acid-reactive
      substances in the lung significantly increased at 2 hrs after platelet-activating
      factor injection. Platelet-activating factor treatment also resulted in an
      increased concentration of total protein, albumin, and Evans blue dye in
      bronchoalveolar lavage fluid at 2 hrs after administration, suggesting platelet
      activating factor induction of increased alveolar permeability. The platelet
      activating factor-induced alveolar microvascular injury, lipid peroxidation, and
      increased alveolar permeability were inhibited by pretreatment with recombinant
      human superoxide dismutase. Although L-NNA alone did not affect alveolar
      permeability in the second set of experiments, L-NNA treatment before platelet
      activating factor challenge significantly aggravated platelet-activating factor
      induced increased alveolar permeability 2 hrs after platelet-activating factor
      challenge. Platelet-activating factor also produced a rapid decrease in blood
      pressure that was not ameliorated by treatment with L-NNA. However, L-NNA
      pretreatment was associated with a significant increase in platelet-activating
      factor-caused mortality within 6 hrs. All rats survived with L-arginine treatment
      before platelet-activating factor challenge. L-NNA treatment decreased
      nitrate/nitrite concentration, an index of total nitric oxide production, in
      plasma. CONCLUSIONS: These results indicate that superoxide, the derived active
      oxygen species, and lipid peroxidation are implicated in the pathogenesis of
      platelet-activating factor-induced acute lung injury. Nitric oxide does not play
      a major role in platelet-activating factor-induced hypotension. Nitric oxide
      appears to play a protective role in the acute lung injury and mortality induced
      by platelet-activating factor.

PMID- 9034268
TI  - High-frequency oscillatory ventilation with partial liquid ventilation in a model
      of acute respiratory failure.
AB  - OBJECTIVE: To determine whether there is an improvement in oxygenation when
      partial liquid ventilation and high-frequency oscillatory ventilation are
      combined in the treatment of acute lung injury, compared with high-frequency
      oscillatory ventilation alone. DESIGN: Controlled animal trial. SETTING: Research
      laboratory in a university setting. SUBJECTS: Ten 3-kg piglets. INTERVENTIONS:
      Anesthetized piglets underwent high-frequency oscillatory ventilation, with mean
      airway pressure of 20 cm H2O, before induction of acute lung injury with repeated
      saline lavage. When PaO2 values were < 100 torr (< 13.3 kPa), five animals were
      randomized to receive escalating doses (3, 15, and 30 mL/kg) of perflubron at 60
      min intervals. The other five animals remained on high-frequency oscillatory
      ventilation only. Sham dosing was performed at 60-min intervals in these animals.
      Arterial blood gases were obtained in both groups at baseline, after injury, and
      after perflubron and sham doses. MEASUREMENTS AND MAIN RESULTS: Statistically
      significant improvements in oxygenation were demonstrated in animals that
      received 3 mL/kg of perflubron with high-frequency oscillatory ventilation
      compared with animals receiving high-frequency oscillatory ventilation alone (253
      +/- 161 vs. 90 +/- 30 torr [33.65 +/- 21.46 vs. 12.0 +/- 4.0 kPa], p < .05).
      Improvements in oxygenation with additional administration of perflubron were not
      greater than the improvements seen in the high-frequency oscillatory ventilation
      only group. PaCO2 and pH were similar in both groups at all times. No hemodynamic
      compromise occurred in either group of animals. CONCLUSIONS: The combination of
      low-dose perflubron with high-frequency oscillatory ventilation leads to more
      rapid improvement in arterial oxygenation than high-frequency oscillatory
      ventilation alone, in a piglet model of acute lung injury. Although the group
      receiving high-frequency oscillatory ventilation alone eventually achieved PaO2
      values that were equivalent to the group receiving high-frequency ventilation and
      perflubron, the combination of perflubron with high-frequency oscillatory
      ventilation may permit effective oxygenation and ventilation at lower mean airway
      pressures by facilitating alveolar expansion and decreasing intrapulmonary shunt.

PMID- 9034267
TI  - Enteral administration of ornithine alpha-ketoglutarate or arginine alpha
      ketoglutarate: a comparative study of their effects on glutamine pools in burn
      injured rats.
AB  - OBJECTIVES: Ornithine alpha-ketoglutarate has proved to be an efficient
      nutritional support in trauma situations, especially after burn injury. To
      determine whether the action of ornithine alpha-ketoglutarate is due to its alpha
      ketoglutarate moiety (as a glutamine precursor), we studied the effects of alpha
      ketoglutarate administered to rats as ornithine alpha-ketoglutarate, or in
      combination with arginine salt (arginine alpha-ketoglutarate), as the two closely
      related amino acids have similar metabolic behavior. DESIGN: Prospective,
      randomized trial. SETTING: Animal laboratory. SUBJECTS: Forty-six male Wistar
      rats, weighing approximately 90 g. INTERVENTIONS: Rats were burned over 20% of
      their body surface area, starved for 24 hrs, with water ad libitum, and then
      enterally refed for 48 hrs using Osmolite (210 kcal/kg/day, 1.2 g of
      nitrogen/kg/day), supplemented with one of the following: a) an amount of glycine
      isonitrogenous to ornithine alpha-ketoglutarate (group 1); b) 5 g of monohydrated
      ornithine alpha-ketoglutarate/kg/day (group 2); c) an amount of arginine alpha
      ketoglutarate isonitrogenous to ornithine alpha-ketoglutarate (group 3); or d) an
      amount of arginine alpha-ketoglutarate isomolar to ornithine alpha-ketoglutarate
      (group 4). MEASUREMENTS AND MAIN RESULTS: We measured amino acid concentrations
      in plasma, muscle, and liver, and plasma urea concentration. At refeeding,
      ornithine alpha-ketoglutarate increased plasma glutamine concentration (p < .05
      vs. the three other groups), and counteracted the increase in plasma
      phenylalanine concentration. In muscle, although the three alpha-ketoglutarate
      combinations induced similar increases in the glutamate pool, ornithine alpha
      ketoglutarate induced the highest increase in glutamine (7.0 +/- 0.3 vs. 5.4 +/-
      0.3 micromol/g in group 3, 6.3 +/- 0.3 in group 4, and 4.6 +/- 0.2 in group 1, p
      < .01 between group 2 and groups 3 or 1). Also, only ornithine alpha
      ketoglutarate increased liver glutamine concentration. Finally, isomolar arginine
      alpha-ketoglutarate increased plasma urea concentration (+50% vs. the three other
      groups, p < .01). CONCLUSIONS: Our results demonstrate, for the first time, the
      following: a) the action of ornithine alpha-ketoglutarate as a glutamine
      precursor cannot solely be ascribed to alpha-ketoglutarate since arginine alpha
      ketoglutarate combinations did not exhibit this effect to the same extent; and b)
      the action of ornithine alpha-ketoglutarate is not due to its nitrogen content
      since isonitrogenous arginine alpha-ketoglutarate did not reproduce the effects
      of ornithine alpha-ketoglutarate.

PMID- 9034269
TI  - Inotropes inhibit endothelial cell surface adhesion molecules induced by
      interleukin-1beta.
AB  - OBJECTIVES: Leukocyte-endothelial cell interactions play a critical role in
      sepsis-induced multiple organ system failure and acute respiratory distress
      syndrome. Increased cyclic adenosine 3',5'-monophosphate (cAMP) has been
      previously reported to inhibit expression of the cytokine-stimulated endothelial
      cell adhesion molecules, E-selectin, and vascular cell adhesion molecule-1 (VCAM
      1). We hypothesized that clinically relevant concentrations of inotropes, such as
      amrinone and dopamine, which increase cAMP, could inhibit cytokine-stimulated
      upregulation of endothelial adhesion proteins. DESIGN: Prospective, controlled in
      vitro study. SETTING: Leukocyte biology laboratory. SUBJECTS: Human umbilical
      vein endothelial cells isolated from neonatal umbilical cord specimens and whole
      blood obtained from normal human adult volunteers were used in this study.
      INTERVENTIONS: Endothelial cell monolayers were pretreated with increasing
      concentrations of amrinone or dopamine, or left untreated as controls, followed
      by exposure to recombinant human interleukin (IL)-1beta for 6 hrs. Monolayers
      were then incubated with monoclonal antibodies to E-selectin, VCAM-1, and
      intercellular adhesion molecule-1 (ICAM-1), fluorescence labeled, and assessed
      for mean fluorescence intensity by flow cytometry as a measure of surface
      adhesion molecule concentrations. Whole blood neutrophils were pretreated with or
      without inotropes, then stimulated with n-formyl methyl leucine phenylalanine.
      Stimulated neutrophils were incubated with antibodies against the neutrophil
      adherence protein CD11b and assessed by flow cytometry. MEASUREMENTS AND MAIN
      RESULTS: IL-1beta markedly increased E-selectin (p = .01), VCAM-1 (p < .01), and
      ICAM-1 (p < .001) concentrations (n = 6). Pretreatment with amrinone
      significantly decreased endothelial E-selectin surface values at all
      concentrations (p < .001 by analysis of variance, n = 5), including therapeutic
      concentration ranges. Amrinone also inhibited upregulation of ICAM-1 (p < .001)
      at therapeutic concentrations, and VCAM-1 (p < .001) at higher concentrations.
      Dopamine inhibited only E-selectin at relevant concentrations. Neutrophil
      pretreatment with inotropes did not prevent CD11b upregulation. CONCLUSIONS:
      Pretreatment with amrinone, and to a lesser degree, with dopamine, at clinically
      relevant concentrations inhibits in vitro IL-1alpha-induced increases in human
      umbilical vein endothelial cell adhesion molecule concentrations. Future studies
      are necessary to investigate the mechanisms of these effects and to determine in
      vivo efficacy of inotropes as anti-inflammatory agents.

PMID- 9034270
TI  - Induction of the heat shock response prevents tissue injury during acute
      inflammation of the rat ileum.
AB  - OBJECTIVES: To determine if prior total body hyperthermia protected against
      subsequent acute ileitis induced by the cytotoxic lectin, ricin, in rats. The
      time course of heat shock mRNA and protein expression in the ileum was
      determined. The effects of heat stress on small intestinal mucosal integrity,
      arachidonic acid metabolism, and neutrophilic infiltrate were compared in heated
      and nonheated rats receiving vehicle or ricin intraluminally. The effect of
      hyperthermia on the circulating neutrophil superoxide production was also
      evaluated. DESIGN: Prospective, randomized, controlled trial. SETTING: University
      research laboratory. SUBJECTS: Forty-one adult, male Sprague-Dawley rats,
      weighing 150 to 250 g, and 32 adult, inbred, male Fisher 344 rats, weighing 175
      to 250 g. INTERVENTIONS: Exposure to whole body hyperthermia and production of
      acute ileitis. Sprague-Dawley rats were divided randomly into four experimental
      groups: nonheated control group, heated control group, nonheated ricin group (1
      mg/mL water, intraluminal), and heated ricin group. Sprague-Dawley rats in a
      separate study were assigned to seven groups based on the time of removal of the
      terminal ileum following hyperthermia: 0 min, or 1, 2, 4, 8, 12, and 24 hrs.
      Inbred Fisher 344 rats were allocated to the heated and nonheated groups for
      peripheral neutrophil superoxide generation studies. MEASUREMENTS AND MAIN
      RESULTS: Whole body hyperthermia to a rectal temperature of 41 degrees C to 42
      degrees C for 15 to 20 mins: a) was associated with marked mucosal cytoprotection
      against subsequent ricin-induced ileitis (Injury grade [from 0 = normal to 5 =
      severe]: 0.4 +/- 0.1 vs. 2.5 +/- 0.2, p < .001); b) prevented the ricin-induced
      reduction in villus height to crypt depth ratio (2.4 +/- 0.1 vs. 1.9 +/- 0.1, p <
      .01); and c) significantly reduced the number of infiltrating neutrophils when
      compared with nonheated ricin-treated rats (11 +/- 2 vs. 32 +/- 3
      neutrophils/high-power field, p < .001). The hyperthermia-induced peak increase
      in heat shock protein (HSP)-70 mRNA at 2 hrs preceded that of HSP 70i at 4 hrs.
      Heat shock significantly reduced the ricin-induced increase in both basal (8.0 +/
      1.9 vs. 33.0 +/- 8.1 pg of leukotriene B4/mg protein, p < .05) and ionophore
      stimulated (16.0 +/- 4.9 vs. 80.0 +/- 15.5 pg of leukotriene B4/mg protein, p <
      .001) generation of ileal leukotriene B4, but did not alter the cyclooxygenase
      product, prostaglandin E2. Hyperthermia did not alter peripheral neutrophil
      superoxide production. CONCLUSIONS: This study assessed the effects of heat shock
      in the normal and acutely inflamed intestine. These data suggest that heat stress
      and increased expression of HSP 70i protect against acute intestinal
      inflammation. This protection is associated with significant reductions in ileal
      leukotriene B4 generation and neutrophilic infiltrate. Hyperthermia did not alter
      circulating neutrophil superoxide production. Thus, the mechanism of heat stress
      protection against acute ileitis may involve local intestinal inhibition of
      leukotriene B4 production and subsequent neutrophilic infiltration without
      altering the ability of systemic neutrophils to be activated.

PMID- 9034271
TI  - Endotoxin differentially impairs cyclic guanosine monophosphate-mediated
      relaxation in the pulmonary and systemic circulations.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of endotoxin on
      alpha1-adrenergic receptor vasoconstriction and both endothelium-dependent and 
      independent cyclic guanosine monophosphate (cGMP)-mediated vasodilation in the
      pulmonary and systemic circulations. DESIGN: Prospective, multiple group,
      controlled experimental study. SETTING: Medical school research laboratory.
      SUBJECTS: Male Sprague-Dawley rats, weighing 250 to 350 g. INTERVENTIONS: Six
      hours after endotoxin (20 mg/kg intraperitoneally) or saline, the response to the
      a) alpha1-adrenergic receptor agonist, phenylephrine; b) endothelium-dependent
      vasodilator, acetylcholine; and c) the endothelium-independent vasodilator,
      sodium nitroprusside, was determined in isolated rat pulmonary artery and
      thoracic aortic rings. MEASUREMENTS AND MAIN RESULTS: Endotoxin caused a
      significant decrease in the response to phenylephrine in the aorta but did not
      affect the response in the pulmonary artery. Endotoxin caused significant
      impairment of relaxation to acetylcholine and sodium nitroprusside in the
      pulmonary circulation. In control rings, only 4 +/- 1% of the preconstricted
      tension remained in response to acetylcholine vs. 77 +/- 3% following endotoxin
      administration (p < .05). Similarly, sodium nitroprusside resulted in complete
      pulmonary ring relaxation in controls vs. 18 +/- 3% tension remaining following
      endotoxin administration (p < .05). On the other hand, only the response to
      acetylcholine was dysfunctional in the thoracic aorta. In thoracic aortic rings
      from control rats, acetylcholine caused complete relaxation; however, 23 +/- 5%
      of the preconstricted tension remained following endotoxin administration. The
      response to sodium nitroprusside in the thoracic aorta from endotoxin-treated
      rats was not different from control. CONCLUSIONS: From these data, we conclude
      that endotoxin causes organ-specific changes in vascular reactivity. These
      changes in vascular reactivity favor a decrease in vascular pressure and
      resistance in the systemic circulation, and an increase in vascular pressure and
      resistance in the pulmonary circulation in response to endotoxin.

PMID- 9034272
TI  - Heat shock protein 70 messenger RNA reflects the severity of ischemia/hypoxia
      reperfusion injury in the perfused rat liver.
AB  - OBJECTIVES: To determine whether ischemia-reperfusion and hypoxia-reoxygenation
      cause cellular damages and stress responses in an isolated perfused rat liver
      model. To determine whether the increased synthesis of stress protein messenger
      RNA reflects cellular injury. DESIGN: Prospective, controlled study. SETTING:
      Institutional laboratories. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS:
      Isolated rat livers with cell free perfusion were exposed to various periods of
      ischemia-reperfusion or hypoxia-reoxygenation. MEASUREMENTS AND MAIN RESULTS: We
      measured hepatic oxygen consumption and alanine aminotransferase leakage from
      liver during perfusion. We analyzed the gene expression of heat shock protein 70,
      a major stress protein, of the liver by Northern blotting after perfusion. The
      expression of heat shock protein 70 messenger RNA augmented as the reperfusion
      period increased. The expression level after graded ischemia or hypoxia
      significantly correlated with the calculated hepatic oxygen debt (r2 = .737; p <
      .001; n = 21), or with the accumulated alanine aminotransferase leakage from the
      liver (r2 = .509; p < .001; n = 21). CONCLUSIONS: These results suggest that the
      accumulation of heat shock protein 70 messenger RNA reflects the severity of
      ischemia-reperfusion and hypoxia-reoxygenation injuries, and that a stress
      response in reperfusion can be triggered without formed elements of blood.

PMID- 9034273
TI  - Gender differences in 24-hour outcome following resuscitation after 9 minutes of
      cardiac arrest in dogs.
AB  - OBJECTIVE: To examine possible gender-specific differences in 24-hr outcome
      following resuscitation from 9 mins of controlled cardiac arrest. DESIGN:
      Preclinical, prospective study comparing two similarly prepared, independent
      control groups (one female group, one male group) included in a larger series of
      studies. SETTING: Physiology research laboratory at a major medical center.
      SUBJECTS: Male and female mongrel dogs (Canis familiaris), weighing 16 to 22 kg.
      INTERVENTIONS: Cardiopulmonary-cerebral resuscitation following 9 mins of
      normothermic cardiac arrest in male vs. female dogs. MEASUREMENTS AND MAIN
      RESULTS: Mean arterial blood pressure, heart rate, urine output, arterial blood
      oxygen, and PCO2 values, arterial pH, temperature, plasma glucose concentrations,
      and hematocrit were measured and recorded at the precardiac arrest and
      postcardiac arrest period, and at 30 mins, and 1, 4, 6, 12, and 24 hrs following
      resuscitation. Neurologic dysfunction was assessed using a well-standardized
      neurologic deficit score assigned at 6, 12, and 24 hrs after arrest. Plasma
      concentrations of malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced
      glutathione were measured at the precardiac arrest period, and 6, 12, and 24 hrs
      following resuscitation. Additionally, serum concentrations of alanine
      aminotransferase, aspartate aminotransferase, total bilirubin, alkaline
      phosphatase, gamma-glutamyl transferase, creatinine kinase, creatinine, albumin,
      and total protein were measured before arrest, and at 6, 12, and 24 hrs after
      resuscitation. Plasma concentrations of inorganic phosphorus, blood urea
      nitrogen, and electrolytes (sodium, chloride, calcium, and potassium) were
      measured. The estrous cycle phase in the female dogs enrolled in the study was
      determined by physical examination and vaginal cytology. No prearrest differences
      were detectable between males and females in basic physiologic variables. No
      differences in neurologic deficit were detectable between males and females
      across the 24-hr recovery period following resuscitation. No detectable
      differences in malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced
      glutathione occurred between groups. Serum concentrations of aspartate
      aminotransferase (p = .02), alanine aminotransferase (p = .009), creatinine
      kinase (p = .01), total bilirubin (p = .05), and plasma concentrations of
      inorganic phosphorus (p = .03), blood urea nitrogen (p = .0003), and creatinine
      (p = .02) all were significantly and dramatically higher in female than male dogs
      at the 24-hr time point. The trend of increase in these values began at the 6-
      and 12-hr time points and was consistent with a steadily decreasing trend in mean
      arterial pressure and an increasing trend in heart rate in the female group.
      CONCLUSIONS: An extensive history with this preclinical canine model (restricted
      to male dogs) had indicated little or no change in standard clinical chemistry
      markers of systemic dysfunction following 9 mins of cardiac arrest. However, when
      compared with male dogs, the female dogs tested here appear to have sustained a
      more significant hepatic and renal ischemic injury with no differences in the
      neurologic deficit.

PMID- 9034274
TI  - In vivo diaphragm metabolism: comparison of paced and inspiratory resistive
      loaded breathing in piglets.
AB  - OBJECTIVE: We hypothesized that spontaneous, loaded diaphragm contractions would
      lead to diaphragm fatigue, which would correlate with inadequate oxidative
      metabolism as measured by phosphorus-31 nuclear magnetic resonance spectroscopy.
      DESIGN: Prospective, randomized, crossover trial. SETTING: University hospital
      research laboratory. SUBJECTS: Eight piglets, 4 to 6 wks of age. INTERVENTIONS:
      Each animal underwent, in random order, a 20-min period of diaphragm pacing and a
      45-min period of loaded spontaneous breathing, separated by a 20-min recovery
      period. Mechanical ventilation was used during diaphragm pacing to maintain a
      PaCO2 of 35 to 45 torr (4.7 to 6.0 kPa) and a PaO2 of > 100 torr (> 13.3 kPa).
      During spontaneous breathing, inspiratory loading was achieved with a 2.0-mm
      inner diameter endotracheal tube in the breathing circuit. MEASUREMENTS AND MAIN
      RESULTS: During pacing, mean transdiaphragmatic pressure decreased by 35%, from
      23 +/- 5 (SD) to 15 +/- 3 mm Hg (p < .05), and this decrease correlated with a
      335% increase in the ratio of inorganic phosphate to phosphocreatine, from 0.23
      +/- 0.1 to 1.0 +/- 0.7 (p < .05). During loaded spontaneous breathing, arterial
      pH decreased from 7.42 +/- 0.06 to 7.25 +/- 0.05 (p < .05), secondary to an
      increase in PaCO2 from 41 +/- 4 to 65 +/- 11 torr (5.3 +/- 0.5 to 8.7 +/- 1.5
      kPa) (p < .05). Despite respiratory acidosis, there was no decrease in
      trandiaphragmatic pressure during the period of loaded breathing, nor was any
      change in the ratio of inorganic phosphate to phosphocreatine seen. CONCLUSIONS:
      Diaphragm fatigue in a pacing model correlates with inadequate oxidative
      metabolism. In contrast, severe inspiratory resistive loaded breathing did not
      result in changes in oxidative metabolism or decreased diaphragm force output,
      despite hypercapnia and respiratory acidosis.

PMID- 9034275
TI  - A randomized, controlled study of prophylactic ranitidine in preventing stress
      induced gastric mucosal lesions in neonatal intensive care unit patients.
AB  - OBJECTIVE: To assess endoscopically the effect of prophylactic short-term
      ranitidine treatment in the prevention of stress-induced gastric lesions in
      neonatal intensive care unit (ICU) patients. DESIGN: Prospective, randomized
      study. SETTING: Department of Neonatal Intensive Care, University Hospital of
      Tampere. PATIENTS: Fifty-three infants were enrolled in a randomized, controlled
      study. Forty-eight (90%) of these patients underwent endoscopic examination and
      were evaluated. INTERVENTIONS: A histamine-2-receptor blocker, ranitidine, was
      given prophylactically after birth for 4 days to infants mechanically ventilated
      and treated in the neonatal ICU. The gastric mucosa was both visually and
      histologically evaluated after 3 to 6 days, and the outcome of the infants was
      registered. MEASUREMENTS AND MAIN RESULTS: In the 23 infants prophylactically
      treated with ranitidine, the gastric mucosa was visually classified as normal in
      14 (61%) infants as compared with five (20%) of 25 controls (p < .004).
      Histologic lesions showed parallel results (57% vs. 16%, p < .004). Eight gastric
      ulcers were diagnosed endoscopically in the control group vs. none in the
      treatment group. The ulcers were all clinically "silent" at the time of
      endoscopy. According to logistic regression modeling, the decreased risk for
      gastric mucosal lesions in infants receiving prophylactic ranitidine was 0.03
      (95% confidence interval 0.003 to 0.178). Surfactant treatment for infant
      respiratory distress syndrome also decreased the risk for stress-induced gastric
      mucosal lesions (odds ratio 0.083; 95% confidence interval 0.009 to 0.788),
      whereas other variables (birth weight, gestational age, Apgar scores, cord blood
      pH, and duration of intubation) had no significant effect. No side effects could
      be attributed to the ranitidine treatment. CONCLUSION: We conclude that short
      term prophylactic ranitidine treatment prevents gastric mucosal lesions in
      newborn infants under stress.

PMID- 9034276
TI  - Inhaled nitric oxide reduces the utilization of extracorporeal membrane
      oxygenation in persistent pulmonary hypertension of the newborn.
AB  - OBJECTIVE: To determine if the use of inhaled nitric oxide therapy reduces the
      need for extracorporeal membrane oxygenation (ECMO) in persistent pulmonary
      hypertension of the newborn. DESIGN: A matched cohort study with retrospective
      data extraction. SETTING: Pediatric and neonatal intensive care units at a
      medical school-affiliated children's hospital serving as a regional referral
      center for respiratory failure. PATIENTS: Records of all neonates transferred for
      rescue therapy for persistent pulmonary hypertension during the study period were
      analyzed, with inclusion in the study based on defined gas exchange parameters,
      and with exclusion from the study based on the presence of congenital heart
      disease, diaphragmatic hernia, or lethal chromosomal abnormality. Assignment to
      cohorts was based on availability of inhaled nitric oxide therapy: group 1
      patients were admitted when inhaled nitric oxide was unavailable; group 2
      patients were admitted when inhaled nitric oxide was available. INTERVENTIONS:
      Standard criteria (alveolar-arterial oxygen tension gradient of > 600 torr [> 80
      kPa], or oxygenation index of > 40) were used to trigger initial evaluation for
      ECMO when these criteria were met for 2 hrs, and ECMO was initiated if these
      criteria continued to be met for 12 hrs, or if cardiovascular instability
      occurred. Ventilator management in all patients was directed to improve arterial
      oxygenation, such that ECMO criteria were no longer met. Patients in group 2 only
      were treated with inhaled nitric oxide after meeting ECMO evaluation criteria,
      and they continued to receive inhaled nitric oxide if a quantifiable improvement
      in gas exchange occurred. MEASUREMENTS AND MAIN RESULTS: Fifty patients qualified
      for inclusion in the analysis (29 patients in group 1, and 21 patients in group
      2). In group 1, 21 (72%) patients met ECMO criteria, and 16 (76%) patients
      required ECMO therapy. In group 2, 16 (76%) patients met ECMO criteria, 15
      patients received inhaled nitric oxide therapy, and only four (25%) patients
      required ECMO therapy (p = .003 compared with group 1). Treatment with inhaled
      nitric oxide resulted in an initial increase in PaO2, without adverse effects, in
      all of the treated patients. The reduction in ECMO utilization in group 2 was
      achieved with a higher rate of complication-free survival (survival without
      oxygen, requirement at 28 days, p = .018; survival without intracranial
      hemorrhage, p = .048), and a lower hospital cost per survivor (p = .021),
      compared with group 1 patients. CONCLUSION: In neonates with persistent pulmonary
      hypertension, therapy with inhaled nitric oxide reliably and safely improves
      oxygenation, thereby resulting in a decreased need for ECMO therapy, improved
      patient outcome, and lower hospital costs.

PMID- 9034277
TI  - Morphine pharmacokinetics during continuous infusion of morphine sulfate for
      infants receiving extracorporeal membrane oxygenation.
AB  - OBJECTIVES: To determine a) if serum morphine concentration changes during the
      first 3 hrs of extracorporeal membrane oxygenation (ECMO); and b) if absorption
      of morphine onto the membrane oxygenator is responsible for these changes. Also,
      morphine clearance during the first 5 days of ECMO was studied. DESIGN:
      Prospective, open-label study with consecutive patient enrollment. SETTING:
      Neonatal intensive care unit at a university-affiliated, children's hospital.
      SUBJECTS: Eleven neonates with severe persistent pulmonary hypertension of the
      newborn receiving continuous intravenous infusions of morphine sulfate and
      requiring ECMO. INTERVENTIONS: Blood samples were obtained from the subjects and
      ECMO circuits at predetermined time intervals. MEASUREMENTS AND MAIN RESULTS:
      Serum morphine concentration was determined using high-performance liquid
      chromatography. Morphine concentrations were no different from baseline at 5
      mins, 1 hr, or 3 hrs after beginning ECMO. There was no significant difference in
      morphine concentration from samples taken immediately proximal and distal to the
      membrane oxygenator at 5 mins, 1 hr, and 3 hrs after the start of ECMO. Morphine
      clearance was calculated on days 1, 3, and 5 of ECMO. The mean value for morphine
      clearance was 11.7 +/- 9.3 (SD) ml/min/kg (range 2.6 to 34.5). CONCLUSIONS: The
      initiation of ECMO does not lead to a significant decrease in serum morphine
      concentration and there is no uptake of morphine onto the membrane oxygenator of
      the ECMO circuit. Morphine clearance for infants receiving ECMO is variable.

PMID- 9034278
TI  - Variation of nitric oxide concentration during inspiration.
AB  - OBJECTIVE: To evaluate the pattern of inspiratory nitric oxide concentration in a
      simple, constant flow delivery system during the use of two phasic-flow
      ventilatory modes. DESIGN: Laboratory study in a lung model. SETTING: University
      experimental laboratory. SUBJECT: Nitric oxide (800 ppm in nitrogen) was
      administered continuously into the inspiratory circuit to deliver a nitric oxide
      concentration of 10 and 40 ppm to a test lung during volume-controlled (constant
      flow) and pressure-controlled (decelerating flow) ventilation, with an FIO2 of
      1.0. INTERVENTIONS: In each mode, minute ventilation of 7, 14, and 21 L/min and
      installation of mixing chambers (none, 1-L, 2-L, and 3.2-L turbulence boxes) were
      studied, respectively. Nitric oxide and nitric dioxide were monitored by
      chemiluminescence. Since the nitric oxide/nitrogen gas is the only nitrogen
      source in the system during ventilation with an FIO2 of 1.0, we evaluated the
      fluctuation in the inspiratory nitric oxide (NOx) concentration by measuring
      nitrogen with a fast-response analyzer. To test the effect of the measurement
      site, we measured nitric oxide concentrations using chemiluminescence at
      different positions in the inspiratory and expiratory limbs, with and without the
      mixing chambers, with a minute ventilation of 14 L/min and a nitric oxide
      concentration of 40 ppm. MEASUREMENTS AND MAIN RESULTS: Nitrogen dioxide
      production was not influenced by the flow pattern. During a nitric oxide
      concentration of 10 ppm, nitrogen dioxide was always < 0.6 ppm. During a nitric
      oxide concentration of 40 ppm, the highest nitrogen dioxide (4.47 ppm)
      concentration was found at the lowest minute ventilation and the largest
      inspiratory circuit volume. Nitric oxide values displayed by chemiluminescence
      indicated stable concentrations at all settings. However, without mixing
      chambers, NOx concentration calculated from nitrogen measurements demonstrated
      marked inspiratory fluctuations and was highest with a minute ventilation of 21
      L/min and higher during pressure-controlled ventilation compared with volume
      controlled ventilation (nitric oxide concentration of 40 ppm, pressure-controlled
      ventilation: 14.5 to 130.5 ppm; volume-controlled ventilation: 21.6 to 104.7 ppm;
      nitric oxide concentration of 10 ppm, pressure-controlled ventilation: 3.2 to
      30.9 ppm; volume-controlled ventilation: 4.5 to 27.1 ppm). NOx concentration
      fluctuation decreased with an increasing mixing chamber, and was negligible at
      all settings with the 3.2-L turbulence box. Nitric oxide concentration
      fluctuation influenced chemiluminescence measurements. The displayed nitric oxide
      values varied, depending on the sampling site, and did not accurately reflect
      mean inspiratory nitric oxide concentration. Incorporation of a mixing chamber
      eradicated this sampling site influence. CONCLUSIONS: Continuous flow delivery of
      nitric oxide into the circuit of a phasic-flow ventilator results in marked
      inspiratory nitric oxide concentration fluctuation that is not detected by a slow
      response chemiluminescence analyzer. Moreover, nitric oxide concentration
      fluctuation can influence the accuracy of the chemiluminescence measurements.
      These effects can be diminished by using additional mixing chambers to facilitate
      a stable gas concentration. As these mixing volumes increase the contact time of
      nitric oxide with oxygen, an increase of nitrogen dioxide has to be taken into
      account.

PMID- 9034279
TI  - Dear SIRS, I'm sorry to say that I don't like you...

PMID- 9034280
TI  - Private attending physician status and the withdrawal of life-sustaining
      interventions.

PMID- 9034281
TI  - A portable nitric oxide scavenging system designed for use on neonatal transport.

PMID- 9034282
TI  - Platelet microparticles and calcium homeostasis in acute coronary ischemias.
AB  - Elevation of free cytoplasmic calcium is the common pathway of platelet
      activation, leading to shape change, shedding of platelet microparticles (PMP),
      aggregation, and secretion of internal granules, including expression of CD62p on
      the surface. Platelet activation is well documented in unstable angina (UA) and
      acute myocardial infarction (MI). We investigated the following markers of
      platelet activation in 55 patients undergoing coronary angiography for suspected
      CAD: free cytoplasmic calcium, [Ca2+]cyt, PMP, CD62p expression, and
      platelet/leukocyte (P/L) interaction. [Ca2+]cyt was measured by Fluo-3 and the
      other measurements were by flow cytometry. Patients were classified into three
      groups: unstable angina (UA, n = 11), recent myocardial infarction (MI, n = 11),
      and patient controls (CTL, n = 33). Blood was drawn before infusion of heparin
      through femoral lines at the time of catheterizaton for assays. ( RESULTS: (1)
      PMP values were significantly higher in both UA and MI than in CTL, P < 0.05.
      There was no difference between UA and MI. (2) P/L interaction was significantly
      elevated only in UA, P < 0.05. (3) CD62p expression on free platelets did not
      differ significantly between any of the three groups. (4) The resting [Ca2+]cyt,
      thrombin-induced Ca2+ influx, and release of Ca2+ from internal stores were all
      significantly higher in platelets from the combined patient group (UA + MI) than
      in the patient control group, P < 0.001 CONCLUSIONS: Results on calcium
      hemostasis and PMP were significantly different in patients with acute coronary
      syndromes than those with stable angina or no coronary ischemia; this may reflect
      underlying pathophysiology of acute coronary ischemia. P/L interaction was higher
      only in the UA group, suggesting a role of leukocytes in UA.

PMID- 9034283
TI  - Thrombotic thrombocytopenic purpura: early and late responders.
AB  - Thrombotic thrombocytopenic purpura (TTP) is characterized by micro-angiopathic
      hemolytic anemia (MAHA), thrombocytopenia, neurological symptoms, renal
      involvement, and fever. We describe our experience in 70 serially encountered TTP
      patients in the last decade who were treated with a standard therapeutic plasma
      exchange (TPE) protocol. Seventy percent of the patients were females. The median
      age of the patients was 43 years (range: 8-80). Sixty patients (85.7%) had a
      complete response to TPE therapy. This represented 91% of 66 who received at
      least one TPE. Ten patients died, two patients died before and two during the
      first plasma exchange. The median number of TPEs performed was nine (range: 1
      85). Thirty-five (58%) out of 60 responded to 3-9 TPEs, and 25 (42%) required 10
      34 TPEs for the response. The median total plasma volume exchanged was 28 liters
      (range: 2.7-250 L) and the mean plasma volumes exchanged during each procedure
      was 3.2 (SD +/- 1.09 L). The patients were classified into early responders (ER)
      and late responders (LR). ERs had a mean platelet count of 180 x 10(9)/L by Day
      5, mean LDH of 643 IU/L by Day 7, and required median of seven TPEs. LRs had a
      mean platelet count of 122 x 10(9)/L by Day 5, mean LDH of 885 IU/L by Day 7, and
      required median of 19 TPEs (P = 0.001). The platelet counts were significantly
      higher (P = 0.01-0.03) in ERs on Days 1, 3, and 5 as compared to LRs but the LDH
      did not differ significantly. Seventy-seven percent of LRs had exacerbation of
      TTP and 18% had relapse as compared to 7% each in ERs. Thirteen patients were in
      coma/semicoma at presentation. Out of these, six died, making coma a bad
      prognostic indicator. Five of the seven survivors in coma had received two single
      plasma volume exchanges on Day 1. In conclusion, 91% of TTP patients had an
      excellent response to plasma exchange therapy with FFR Coma/ semicoma appears to
      be a bad prognostic indicator. LRs needed prolonged treatment with a greater
      number of patients experiencing exacerbation and relapse of TTP as compared to
      ERs.

PMID- 9034284
TI  - Laboratory diagnosis of anemia and related diseases using multivariate analysis.
AB  - To establish a simple computer program for the laboratory diagnosis of anemia and
      related diseases, multivariate analyses were applied to the results of routine
      hematological laboratory tests obtained from 48 patients and 51 healthy
      volunteers. The patients studied were limited to those who had not been treated
      hematologically by the time of their first visit to our hospital, and their first
      data obtained in our laboratory were analyzed. Final diagnoses were aplastic
      anemia (AA) in 21, myelodysplastic syndrome (MDS) in 14, iron deficiency anemia
      (IDA) in 3, polycytemia vera (PV)in 3, and idiopathic thrombocytopenic purpura
      (ITP) in 7. Eight parameters, WBC, RBC, Hb, Ht, MCV, MCH, MCHC, and PLT, were
      transformed to normal distribution and then applied to principal component
      analysis to evaluate their independence. Very close relationships were observed
      between Ht and Hb, and between MCV and MCH. One each of these pairs was selected
      by discriminant analysis and two sets, RBC, MCH, Hb, PLT, and WBC, and RBC, MCV,
      Ht, PLT, and WBC, were obtained. Two canonical components gave good
      discrimination of these five diseases and also of normal subjects. When disease
      prediction was made using this analysis, 37 of 48 patients (77.1%) were predicted
      correctly, and furthermore, when two disease predictions were allowed, all
      patients were diagnosed properly. Some overlaps were observed in this two
      dimensional coordinate system, especially of AA and MDS, and also with normal
      subjects. To improve the system further, the additional parameters of age and sex
      were added to construct a three-dimensional analysis which resulted in much
      clearer discrimination. The whole procedure described is being developed with
      subjects who are not taking medication. Subsequently, the general application of
      this analytical procedure should be limited to only those not on medications. In
      conclusion, this is in essence a demonstration project; however, this trial of
      laboratory diagnosis using routine hematological laboratory results appears to be
      promising. Further extension of the study by increasing numbers of patients and
      disorders studied, including secondary anemias, will allow the design of
      diagnostic software for use with personal computers at the sites of primary care.

PMID- 9034285
TI  - Effect of human urinary thrombomodulin on endotoxin-induced intravascular
      coagulation and pulmonary vascular injury in rats.
AB  - Adult respiratory distress syndrome (ARDS) and disseminated intravascular
      coagulation (DIC) are serious complications of sepsis. Thrombomodulin, an
      important endothelial anticoagulant, binds thrombin to generate activated protein
      C (APC). To determine whether thrombomodulin purified from human urine (urinary
      thrombomodulin, UTM) is useful for the treatment of DIC and ARDS in sepsis, we
      examined the effect of UTM on endotoxin (ET)-induced coagulation abnormalities
      and pulmonary vascular injury in rats. Intravenous administration of UTM
      prevented the ET-induced pulmonary accumulation of leukocytes and the increase in
      pulmonary vascular permeability, as well as ET-induced histological changes such
      as leukocyte infiltration and pulmonary interstitial edema. On the other hand,
      dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective
      inhibitor of thrombin generation, did not prevent these effects of ET. UTM did
      not prevent ET-induced pulmonary accumulation of leukocytes and pulmonary
      vascular injury in rats pretreated with DEGR-Xa. Our findings suggest that UTM
      attenuates ET-induced coagulation abnormalities and pulmonary vascular injury.
      Furthermore, the latter effect may be dependent on the capacity of UTM to
      activate protein C.

PMID- 9034286
TI  - Pharmacokinetics of intravenous recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) in children receiving myelosuppressive cancer chemotherapy:
      clearance increases in relation to absolute neutrophil count with repeated
      dosing.
AB  - Limited evidence suggests increased efficacy of rhG-CSF by subcutaneous (SQ)
      compared with intravenous (IV) administration. To examine the possibility that
      rapid elimination of IV rhG-CSF could substantially shorten the duration of
      systemic exposure and could explain a difference in pharmacodynamics, we
      characterized the pharmacokinetic profile of IV rhG-CSF for comparison to that
      previously reported for SQ administration. Twelve children were randomly assigned
      to receive 10 or more days of IV rhG-CSF at dosages of 5 or 10 microg/kg a day
      beginning 24 hr after chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was
      used to measure rhG-CSF concentrations in timed serum samples on days 1 and 10.
      Pharmacokinetic parameters were estimated by nonlinear, least squares regression.
      All serum concentration-time profiles were best described by a two-compartment
      model of elimination. Mean t1/2beta values ranged from 3.68 +/- 0.86 to 22.4 +/-
      12.0 hr. ANC was correlated with log CLT (r = 0.72, P < 0.05), and inversely with
      log dose-adjusted AUC (r = 0.75, P < 0.05) and log dose-adjusted Cmax (r = -0.65,
      P < 0.05). Estimated duration of serum rhG-CSF concentrations above 1 ng/ml
      exceeded 24 hr for all but the 5 microg/kg cohort on day 1. Pharmacokinetic
      parameters of IV rhG-CSF are similar to those previously reported for SQ
      administration in children treated with myelosuppressive cancer chemotherapy.
      Daily IV administration should be a suitable alternative route of administration
      in this patient population.

PMID- 9034287
TI  - Infectious morbidity in long-term survivors of allogeneic marrow transplantation
      is associated with low CD4 T cell counts.
AB  - Survivors of allogeneic marrow transplants are immunodeficient for at least 1
      year after grafting. Multiple defects of immunity have been found; however, it is
      not known which defect primarily accounts for the high infectious morbidity of
      these patients. Twenty-nine allograft recipients who were in complete remission
      of the original disease were examined for the following parameters of immunity at
      1 year after transplant: infection score (gauging the number and severity of
      infections within the 6 months prior to the annual exam), serum total IgM, IgG,
      and IgA, anti-Haemophilus influenzae IgG, anti-Streptococcus pneumoniae IgG, skin
      test reactivity, and the blood counts of B cells, CD4+ T cells, CD8+ T cells, and
      their subsets. THe only parameter inversely correlated with the infection score
      was CD4+ T cell count (P = 0.005 in univariable analysis, P = 0.06 in
      multivariable analysis). We conclude that infectious morbidity of long-term
      transplant survivors is related to the reconstitution of CD4+ T cells.

PMID- 9034288
TI  - Acquired von Willebrand's disease: a concise review.
AB  - Acquired von Willebrand's disease (AvWD), an adult-onset bleeding diathesis, has
      most commonly been found in patients with an underlying lymphoproliferative
      disease or monoclonal gammopathy. Other malignancies, autoimmune diseases,
      hypothyroidism, and drugs have also been associated with AvWD. We have included
      an illustrative case history of a patient with a bleeding diathesis consistent
      with AvWD and a monoclonal gammopathy who required emergent cardiac surgery. Our
      review of the literature determined that most cases of AvWD are due to a
      circulating antibody that combines with the high molecular weight multimers
      (HMWM) of von Willebrand factor (vWF). These vWF multimer-antibody complexes are
      subsequently cleared from the circulation either by the reticuloendothelial
      system or by adsorption onto tumor cells. Clearance of the HMWM of vWF thus
      results in extremely low functional levels and variable antigenic levels. Mixing
      studies which are traditionally used to diagnose factor inhibitors are useful
      only if removal of vWF-antibody complexes can be accomplished in vitro. Treatment
      with intravenous immunoglobulin has recently been shown to be the most effective
      therapy for patients with an underlying lymphoproliferative disorder or
      monoclonal gammopathy. This therapeutic strategy is based on the observed immune
      complex clearance phenomenon that appears to be operative in most cases. Other
      AvWD-associated diseases require treatment specifically directed at the
      underlying disorder.

PMID- 9034289
TI  - Immune thrombocytopenia in postpolythemic myelofibrosis.

PMID- 9034290
TI  - Danazol for paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal stem-cell disorder in
      which blood cells lack complement inhibiting membrane proteins, and become
      susceptible to complement-mediated injury, leading to chronic intravascular
      hemolysis and pancytopenia. Glucocorticoids have been a mainstay of therapy. For
      patients refractory to glucocorticoids and requiring blood transfusions, an
      alternative therapy is needed. We studied danazol therapy in 5 patients
      refractory to other treatments. Four of the 5 benefited, showing rise in
      hematocrit and eventual cessation of transfusion requirements. Remissions lasted
      > or =2 years in 3 and 10 years in 1 patient. Danazol was well-tolerated without
      serious side effects. Danazol appears to be a good alternative treatment in PNH.

PMID- 9034291
TI  - Chronic relapsing thrombotic thrombocytopenic purpura and antiphospholipid
      antibodies: a report of two cases.
AB  - We report on 2 cases of chronic relapsing thrombotic thrombocytopenic purpura, in
      which anti-phospholipid antibodies were also found. The first patient was felt to
      have the anti-phospholipid antibody syndrome, while the second patient had anti
      phospholipid antibodies without clinical manifestations of the anti-phospholipid
      antibody syndrome. We discuss chronic relapsing thrombotic thrombocytopenic
      purpura and the anti-phospholipid antibody syndrome. Furthermore, we introduce
      the possibility of an association between chronic relapsing thrombotic
      thrombocytopenic purpura and the presence of anti-phospholipid antibodies.

PMID- 9034292
TI  - beta-Thalassemia and hemoglobin types in Argentina: determination of most
      frequent mutations.
AB  - In order to know the spectrum of beta-thalassemia alleles and other mutations
      affecting the beta-globin gene, we analyzed the hemoglobin abnormalities in 24
      patients from the Province of Cordoba in Argentina. Molecular screening of
      samples was performed by the polymerase chain reaction (PCR), using six sets of
      oligonucleotides to amplify fragments encompassing the whole beta-globin coding
      region and splice junctions, as well as the promoter and 3' untranslated regions.
      The altered fragments were determined by denaturing gradient gel electrophoresis
      (DGGE), and the corresponding mutations were identified by restriction enzyme
      analysis or by direct sequencing of PCR products. Using this approach, three
      different beta-thalassemia mutations were detected, codon 39 (C-->T), IVS-1-110
      (G-->A), and IVS-1-1 (G-->A), and also the hemoglobin S trait. This is the first
      report of beta-thalassemia mutations described in Argentina. Our results show
      that these mutations are similar to those found in Spain and Italy, possibly due
      to the important Mediterranean migratory stream received in our country, and
      could be important for prenatal diagnosis of these diseases in Cordoba,
      Argentina.

PMID- 9034294
TI  - Myelodysplastic features in juvenile rheumatoid arthritis.
AB  - We have attempted to investigate the dysplastic changes in the hematopoietic
      system associated with juvenile rheumatoid arthritis (JRA) and its relation to
      disease activity. The peripheral blood smear and bone marrow aspiration samples
      of 17 JRA patients were investigated and correlations with laboratory parameters
      of disease activity sought. The age range was 6-16 years and the duration of
      disease 1.5-108 months. Abnormal finding of the peripheral smear and bone marrow
      were scored separately. The score of pathological peripheral blood findings
      correlated significantly with CRP and ferritin (both P <0.05). In the bone marrow
      specimens marked changes were noted in the myeloid, erythropoietic, and
      megakaryopoietic series; however, the score of pathological findings did not
      correlate with laboratory parameters of disease activity (P > 0.05). We suggest
      that JRA is associated with marked myelodysplastic changes, also manifested in
      the peripheral blood smear; these changes may well be the consequence of the
      inflammatory milieu, including cytokines, during active disease.

PMID- 9034293
TI  - Hb S/Hb Lepore with mild sickling symptoms: a hemoglobin variant with mostly
      delta-chain sequences ameliorates sickle-cell disease.
AB  - Three cases are reported of Hb S/Hb Lepore combination with very mild sickling
      manifestations. The presence of a nonalpha-chain variant with a high proportion
      of delta chain sequences, including 22 ala, appears to ameliorate sickle-cell
      disease. Efforts to increase the proportion of Hb A2 may be beneficial in sickle
      cell disease.

PMID- 9034295
TI  - Disseminated aspergillosis after mobilization with intensive chemotherapy prior
      to autologous stem-cell transplant in chronic myeloid leukemia.

PMID- 9034296
TI  - Interleukin-6 and cancer-related hypoaldosteronism.

PMID- 9034297
TI  - Plasma protein Z levels in early respiratory distress syndrome.

PMID- 9034298
TI  - Danazol in refractory pruritus of myeloproliferative disorders.

PMID- 9034299
TI  - Bulky plasmacytoma of the skull with intracranial involvement.

PMID- 9034300
TI  - Clumping of plasma cells: a pitfall in the diagnosis of plasma cell leukemia.

PMID- 9034301
TI  - It's time to define "EBV-associated lymphomas".

PMID- 9034302
TI  - Thrombotic thrombocytopenic purpura caused by ticlopidine, successfully treated
      by plasmapheresis.

PMID- 9034303
TI  - Specific cutaneous involvement indicating relapse of Burkitt's lymphoma.

PMID- 9034304
TI  - Microcytic anemia with iron malabsorption.

PMID- 9034305
TI  - Protein interaction cloning in yeast of the mouse third largest RNA polymerase II
      subunit, mRPB31.
AB  - The cDNA encoding a protein that interacts with the mouse homologue of the yeast
      RNA polymerase II (polII) subunit, RPB11, and the human polII subunit, hRPB14,
      has been isolated by protein interaction cloning. Its deduced amino acid sequence
      has 96% homology to the human third largest polII subunit, hRPB33 [Pati and
      Weissman (1990) J. Biol. Chem. 265, 8400 8405]. Therefore, we conclude that the
      cloned cDNA encodes the mouse third largest polII subunit, mRPB31. Isolation of
      cDNA by protein interaction cloning provides evidence supporting the hypothesis,
      first proposed for human polII assembly [Pati (1994) Gene 145, 289-292], that the
      mRPB31/mRPB14 heterodimer, rather than the mRPB31 homodimer, forms in the mouse
      polII assembly. Indeed, in the yeast two-hybrid system, mRPB31 was shown to fail
      to form homodimer.

PMID- 9034306
TI  - A novel bacterial vector system for monitoring protein-protein interactions in
      the cAMP-dependent protein kinase complex.
AB  - A bacterial expression vector is described for investigation of protein-protein
      interactions. Important features of the vector include partition of the cI
      repressor of bacteriophage lambda into two functional domains separated by a
      multicloning site, and low level auto-regulated expression of human genes as C
      terminal fusions to the DNA-binding domain of cI. Two different reporter systems
      have been employed; expression of either a suppressor tRNA or the alkaline
      phosphatase gene is dependent in both cases on the extent of repression of the
      major leftward promoter of lambda (lambdaP(L)). The cAMP-dependent protein kinase
      (PKA) has been used as a model protein complex because both homodimer and
      heterodimer interactions are known to occur and because cAMP acts as a modulator
      of these interactions. It has been shown that the product of the repressor gene
      with newly incorporated expressed polylinker restriction sites still functions as
      a repressor. Substitution of the dimerisation domain of the cI repressor with the
      regulatory subunit of PKA does not diminish the ability of a cI fusion protein to
      repress expression of the reporter gene from lambdaP(L), indicating that the
      regulatory subunit of PKA dimerises the fusion protein in the Escherichia coli
      cytoplasm. Substitution instead with the catalytic subunit of PKA destroys the
      repression ability of cI, which is partially restored by separate expression of
      the regulatory subunit within the same cell. Complete restoration is achieved
      using a host E. coli strain which has lost its ability to synthesise cAMP and
      again this can be reversed by the addition of exogenous cAMP to these cells.
      Human PKA has been reconstituted in the E. coli cytoplasm, where all subunit
      interactions appear functional and respond as expected to the allosteric
      modulator cAMP.

PMID- 9034308
TI  - Cloning of the cDNA encoding rat homologue of the mismatch repair gene MSH2 and
      its expression during spermatogenesis.
AB  - A rat cDNA clone encoding the mismatch repair protein MSH2 has been isolated and
      characterized. The cDNA has an open reading frame of 2802 nucleotides in length
      coding for a protein of 933 amino acids (100 kDa). It shows significant homology
      to human and mouse MSH2. Northern blot analysis of rat MSH2 in the testes of rats
      of different ages showed maximum expression at 20 days, at which time the germ
      cells are undergoing premeiotic DNA replication. We observed down-regulation in
      the expression of rat MSH2 beyond 25 days by which time the germ cells have
      entered meiotic prophase.

PMID- 9034307
TI  - A search for a mammalian homologue of the Drosophila photoreceptor development
      gene glass yields Zfp64, a zinc finger encoding gene which maps to the distal end
      of mouse chromosome 2.
AB  - Whilst searching for a mammalian homologue of the Drosophila glass gene we cloned
      a mouse cDNA whose deduced sequence encodes a 614 amino acid (aa) protein with
      ten Cys2-His2 (C2H2) zinc finger (Zf) motifs. Zfp64 is expressed in all
      developing and mature mouse tissues examined, except the mouse erythroleukemia
      (MEL) cell line. Zfp64 maps to the distal region of mouse chromosome 2 close to
      lens opacity 4 (Lop4), a semidominant cataract mutation. Sequence analysis shows
      that Zfp64 has multiple potential phosphorylation sites for casein kinase II (CK
      II), protein kinase C (PKC), tyrosine kinase (TK) and c-AMP- and c-GMP-dependent
      protein kinase (cA/GMPDPK).

PMID- 9034309
TI  - Extending filamentous phage host range by the grafting of a heterologous receptor
      binding domain.
AB  - fd and IKe are two similar filamentous phage which infect their hosts by means of
      pili found on the host membrane: fd infects bacteria bearing F pili, whereas IKe
      infects bacteria bearing N or I pili. Infection is mediated by the gene 3 protein
      (g3p), which of the nine proteins found in both phage is the most diverse.
      Previous attempts to incorporate g3p from one phage into the other by
      complementation have been unsuccessful [Bross et al. (1988) J. Gen. Microbiol.
      134, 461-471]. Here we have grafted different parts of IKe g3p to the end of fd
      g3p and so augmented the host range of fd phage. We show that phage bearing such
      chimeric g3p are able to infect bacteria bearing both N and F pili providing they
      contain at least the receptor domain of IKe g3p, the infection of N bearing
      bacteria occurring at a level 70,000 times greater than background. This level of
      infection can be increased tenfold by including the glycine-rich domain as well.
      Addition of the penetration domain does not improve the level of infection above
      that of the receptor domain alone, indicating that the fd penetration domain is
      functional in the infection of bacteria bearing either N or F pili. Similarly
      derived fd phagemid also show increased infection of bacteria bearing N pili,
      albeit at much lower levels, suggesting that efficient infection requires more
      than one functional g3p on the surface of the phage.

PMID- 9034310
TI  - Isolation and characterization of the carotenoid biosynthesis genes of
      Flavobacterium sp. strain R1534.
AB  - The Gram-negative bacterium Flavobacterium sp. strain R1534 is a natural producer
      of zeaxanthin. A 14 kb genomic DNA fragment of this organism has been cloned and
      a 5.1 kb piece containing the carotenoid biosynthesis genes sequenced. The
      carotenoid biosynthesis cluster consists of five genes arranged in at least two
      operons. The five genes are necessary and sufficient for the synthesis of
      zeaxanthin. The encoded proteins have significant homology to the crtE, crtB,
      crtY, crtI and crtZ gene products of other carotenogenic organisms. Biochemical
      assignment of the individual gene products was done by HPLC analysis of the
      carotenoid accumulation in Escherichia coli host strains transformed with
      plasmids carrying deletions of the Flavobacterium sp. strain R1534 carotenoid
      biosynthesis cluster.

PMID- 9034311
TI  - The rfaD locus: a region of rearrangement in Vibrio cholerae O139.
AB  - We analyzed the rfaD locus of the novel epidemic Vibrio cholerae strain O139, a
      putative region of rearrangement. This region includes 4 orfs in the same
      orientation. Two orfs, rfaD(O139) and orf2(O139) were almost identical to those
      described in V. cholerae O1. In contrast, the two other orfs upstream from
      rfaD(O139), designated orfA(O139) and orfB(O139), were absent from V. cholerae
      O1, but present in environmental strains of V. cholerae O22, O141 and O155. These
      results suggest that a chromosomal rearrangement might have occurred in the
      vicinity of rfaD in V. cholerae O1, resulting in the emergence of V. cholerae
      O139. The putative source of exogenous DNA might have been V. cholerae O22, O141
      and O155.

PMID- 9034312
TI  - Classification of catechol 1,2-dioxygenase family: sequence analysis of a gene
      for the catechol 1,2-dioxygenase showing high specificity for methylcatechols
      from Gram+ aniline-assimilating Rhodococcus erythropolis AN-13.
AB  - Gram+ aniline-assimilating Rhodococcus erythropolis AN-13 (AN-13) produces
      catechol 1,2-dioxygenase (C12O) showing high enzymatic activities for 3- and 4
      methylcatechols [Aoki et al. (1984) Agric. Biol. Chem. 48, 2087-2095]. A 3.0 kb
      Sau3AI fragment carrying a gene encoding C12O(catA) was cloned by selection of
      transformants showing C12O activity from a gene library of AN-13. Furthermore, we
      specified a 1.6 kb SalI fragment containing catA from the Sau3AI fragment by
      subcloning. Sequence analysis revealed that the 1.6 kb SalI fragment carried a
      855 bp open reading frame (ORF) encoding the entire AN-13 catA, preceded by a
      potential ribosome binding site (RBS). From comparison of the deduced amino acid
      (aa) sequence of C12O from AN-13 with other C12O reported previously, it was
      found that the AN-13 enzyme shares 56.0% aa sequence identity with C12o from
      Arthrobacter sp. mA3 (mA3) [Eck and Belter (1991) Gene 123, 87-92] compared with
      less than 36.4% aa sequence identities with others. In conclusion, we classified
      all C12O including the AN-13 enzyme into three subfamilies on the basis of
      similarity of aa sequences, numbers of aa residues, and substrate specificity.

PMID- 9034313
TI  - Evidence for regulation of transcription and replication of the human neurotropic
      virus JCV genome by the human S(mu)bp-2 protein in glial cells.
AB  - Glial factor 1 (GF-1) is a partial cDNA isolated from a human brain cDNA library
      which encodes a truncated protein with binding ability to the B-regulatory domain
      of the human neurotropic virus, JCV. GF-1 exhibits sequence homology to the
      central region of the newly identified human DNA-binding protein S(mu)bp-2. GF-1
      appears to be a partial cDNA for human S(mu)bp-2 based on its sequence homology
      to S(mu)bp-2 and their chromosomal co-localization. In this report, we have
      employed transfection assay and have compared the ability of GF-1 and its full
      length form, S(mu)bp-2, on regulating the activity of JCV promoters in glial
      cells. Our results demonstrate that, unlike GF-1 which stimulates JCV early
      promoter in glial cells, overexpression of S(mu)bp-2 exhibits no drastic effect
      on the transcription of the viral early promoter. The activity of the viral late
      promoter was noticeably increased by both GF-1 and S(mu)bp-2, although the level
      of induction by GF-1 was consistently higher than that detected by S(mu)bp-2. Use
      of deletion constructs in co-transfection assay revealed that the B-domain of the
      JCV promoter is required for transcriptional activation by GF-1 and S(mu)bp-2.
      Expression of GF-1 and S(mu)bp-2 in glial cells increased the induced level of
      JCV late gene transcription by the viral early protein, T-antigen. Examination of
      the viral DNA replication by DpnI assay indicated that, unlike GF-1, S(mu)bp-2
      has the ability to decrease the level of JCV DNA replication in glial cells.
      These observations suggest that the N-terminal portion of S(mu)bp-2 which
      encompasses several helicase motifs and/or its C-terminus, both of which are
      missing in GF-1, may confer differential effects on viral gene transcription and
      replication. The biological importance of our findings in regulation of the JCV
      lytic cycle in glial cells is discussed.

PMID- 9034314
TI  - Identification of a functional homolog of the Escherichia coli and Salmonella
      typhimurium cysM gene encoding O-acetylserine sulfhydrylase B in Campylobacter
      jejuni.
AB  - The final step of L-cysteine biosynthesis in Escherichia coli and Salmonella
      typhimurium consists of the formation of L-cysteine from O-acetylserine and
      sulfide. This reaction can be catalyzed by two enzymes, O-acetylserine
      sulfhydrylase A and O-acetylserine sulfhydrylase B, the former of which has been
      more rigorously characterized. In contrast to O-acetylserine sulfhydrylase A, O
      acetylserine sulfhydrylase B is preferentially used for cysteine biosynthesis
      during anaerobic growth and is able to utilize thiosulfate as a substrate.
      Campylobacter jejuni is a micro-aerophilic, Gram-negative bacterium, and a member
      of the epsilon subdivision of eubacteria. We have cloned, sequenced, and
      expressed a gene from C. jejuni that encodes a protein of 299 aa with a
      calculated molecular mass of 32,367 Da. Complementation analysis of an E. coli
      cysteine auxotroph with the pMEK34-14 recombinant plasmid containing a 1.2-kb
      insert of chromosomal DNA from C. jejuni revealed that transformants were capable
      of growth in medium containing either sulfide or thiosulfate as sole sulfur
      sources. These data indicate that the cloned C. jejuni gene is a functional
      homolog of the cysM gene that codes for O-acetylserine sulfhydrylase B in E. coli
      and S. typhimurium.

PMID- 9034315
TI  - Characterization of a domain of the genome of BmNPV containing a functional gene
      for a small capsid protein and harboring deletions eliminating three open reading
      frames that are present in AcNPV.
AB  - The nucleotide sequence of a 1.5-kb fragment of the genome of Bombyx mori nuclear
      polyhedrosis virus (BmNPV) has been determined. An open reading frame (ORF) has
      been identified, which encodes a protein of a predicted molecular mass of 15 kDa
      (p15). Analysis of the p15 sequence revealed that it shares significant
      similarities with a number of previously characterized viral capsid proteins. Two
      mRNAs, 0.7- and 1.3-kb, are transcribed from the p15 gene. The 0.7-kb transcript
      appears before BmNPV DNA replication, while the 1.3-kb transcript is transcribed
      only after viral DNA replication. The transcription start sites for the 0.7- or
      1.3-kb transcripts have been localized into two areas mapping 114 and 557/559 bp
      upstream of the p15 translation initiation codon, respectively, and the two
      transcripts appear to share a common poly(A) addition site located 114 bp
      downstream of the translation termination codon. Comparisons of the nucleotide
      sequence of the 1.5-kb BmNPV fragment with that of another isolate of BmNPV and
      with Autographa californica NPV (AcNPV) genomic DNA reveal that the corresponding
      region of AcNPV encompasses 4.1 kb of DNA and three additional ORFs that are
      absent from the BmNPV genome. These findings raise questions about the origin and
      functional relevance of the putative polypeptides encoded by the three ORFs of
      AcNPV.

PMID- 9034316
TI  - Isolation and characterization of a mammalian homolog of the Drosophila white
      gene.
AB  - The Drosophila melanogaster white gene is a member of the ABC transporter
      superfamily of ATPase transmembrane proteins and is involved in the cellular
      uptake of guanine and tryptophan. We have cloned and sequenced human and mouse
      homologs of white which share 55-58% amino acid similarity with the Drosophila
      protein. Northern analysis reveals that the mammalian homolog is highly expressed
      in several tissues, including brain, spleen, lung and placenta. We have localized
      the gene to human chromosome 21q22.3 by means of fluorescence in situ
      hybridization and linkage analysis using a (CA)n polymorphism. The human homolog
      maps to the interval between D21S212 and D21S171, a region which includes loci
      for bipolar affective disorder and a recessive form of deafness. Since tryptophan
      is a precursor for the neurotransmitter serotonin and neurotoxic metabolites of
      the kynurenine pathway, we propose that the human homolog of white is a suitable
      candidate gene for these neurological disorders in humans.

PMID- 9034317
TI  - Molecular cloning of gilthead seabream (Sparus aurata) pituitary transcription
      factor GHF-1/Pit-1.
AB  - We report here the complete nucleotide sequence of a cDNA clone encoding Sparus
      aurata GHF-1/Pit-1 isolated from an expression library prepared from gilthead
      seabream pituitary gland poly(A)+ RNA. The cDNA sequence (saGHF-1/Pit-1) encodes
      a protein of 371 amino acids (aa) containing a POU domain (aa 194-343) and a
      transactivation, STA domain (aa 1-128). Northern blot hybridization of pituitary
      RNA detected a single 3.0 kb band and a rat GHF-1/Pit-1 antiserum was found to
      immunoreact with pituitary protein species of 42 kDa by Western blot analysis.
      When compared with mammalian GHF-1/Pit-1 aa sequence, the POU and STA domains of
      saGHF-1/Pit-1 protein show 83% and 48% aa identity, respectively. In spite of the
      low homology of the transactivation domain, saGHF-1/Pit-1 is able to activate the
      transcription of the human growth hormone promoter.

PMID- 9034318
TI  - The gene encoding bovine brain-derived neurotrophic factor (BDNF).
AB  - We present the nucleotide (nt) sequence for the cDNA encoding bovine brain
      derived neurotrophic factor (BDNF). The nt and peptide sequences were compared to
      those of other BDNF genes from other species.

PMID- 9034319
TI  - A Leuconostoc lactis protein with homology to ribosomal protein S1 shares common
      epitopes and common DNA binding properties with a mammalian DNA binding nuclear
      factor.
AB  - A mouse testis cDNA expression library (Clontech) was screened with a synthetic
      oligonucleotide ligand containing CT-rich motifs derived from the rat skeletal
      muscle actin gene promoter. These motifs bind nuclear proteins, and seem to be
      involved in the regulation of the gene. Analysis of isolated clones, which
      expressed proteins that specifically bind the oligonucleotide, indicated that
      they were derived from a single gene. This gene was identified as a contaminant
      of bacterial origin (Leuconostoc lactis). The cloned gene from L. lactis encodes
      a protein with significant homology to bacterial ribosomal protein S1, which we
      designated LrpS1-L. Band shift analysis and competition experiments indicated
      that both the bacterial protein and a mouse nuclear protein specifically bind to
      the same CT-rich motif of the skeletal muscle actin promoter. Furthermore,
      antibodies against the recombinant bacterial protein interfered with the
      formation of complex between the CT-rich element and the mouse nuclear protein.
      These results indicate that the bacterial LrpS1-L protein and the mammalian
      protein bind the same CT-rich motif and share common antigenic epitopes.

PMID- 9034320
TI  - Cloning and expression of AatII restriction-modification system in Escherichia
      coli.
AB  - The genes encoding the AatII restriction endonuclease and methylase from
      Acetobacter aceti have been cloned and expressed in Escherichia coli. The
      nucleotide sequences of aatIIM and aatIIR genes were determined. The aatIIM and
      aatIIR genes are 996 bp and 1038 bp, respectively, encoding the 331-aa methylase
      with a predicted molecular mass of 36.9 kDa, and the 345-aa AatII restriction
      endonuclease with a predicted molecular mass of 38.9 kDa. The two genes overlap
      by 4 base pairs and are transcribed in the same orientation. The aatIIRM genes
      are located next to a putative gene for plasmid mobilization. A stable
      overproducing strain was constructed, in which the aatIIM gene was expressed from
      a pSC101-derived plasmid. The aatIIR gene was inserted into a modified T7
      expression vector that carries transcription terminators upstream from the T7
      promoter. The recombinant AatII restriction endonuclease was purified to near
      homogeneity by chromatography through DEAE Sepharose, Heparin Sepharose, and
      phosphocellulose columns.

PMID- 9034321
TI  - A simple screening for mutant DNA binding proteins: application to murine
      transcription factor PEBP2alpha subunit, a founding member of the Runt domain
      protein family.
AB  - Mouse transcription factor PEBP2 (polyomavirus enhancer-binding protein (2) is
      composed of two distinct subunits alpha and beta. The alpha subunit has an
      ability to bind the specific DNA sequences, which is enhanced by formation of a
      heterodimer with the beta subunit. The DNA binding and heterodimerization
      activities of the alpha subunit are both localized within a 128-amino-acid (aa)
      region termed as the Runt domain for its homology to the Drosophila segmentation
      gene runt. To characterize the molecular determinants for these activities, the
      Runt domain was randomly mutagenized and produced in E. coli as a secreted form.
      Using E. coli culture supernatant, the DNA binding and heterodimerization of
      mutant Runt domains were analyzed by gel retardation assay. Nine randomly picked
      single-aa substitution mutants showed various functional alterations in DNA
      binding and heterodimerization either separately or simultaneously. This
      observation suggests that the structure of Runt domain is highly ordered and is
      quite sensitive to modulations in its primary structure. The method presented
      here provides a simple and quick method to characterize a large number of mutant
      DNA binding proteins.

PMID- 9034322
TI  - Characterization of the genes encoding integrative and excisive functions of
      Lactobacillus phage og1e: cloning, sequence analysis, and expression in
      Escherichia coli.
AB  - og1e is a temperate phage of the Lactobacillus strain G1e. The phage-host
      junctions attR and attL cloned from the lysogen have a 24-bp common (core)
      sequence implicated in recombination. DNA sequencing analysis of a 5.2-kbp SacI
      fragment of the og1e phage genome (42.5 kbp) revealed two possible open reading
      frames (ORF), xis and int, and the phage attachment (recombination) site (attP),
      whose 24-bp sequence is identical to the core sequence detected in attR and attL.
      The deduced int product (Int) is a basic protein of 391 amino acids with an
      estimated pI of 9.70, and significantly resembles other presumed integrases
      encoded by the Lactobacillus and Lactococcus phages including oadh and oLC3, as
      well as the Escherichia coli phages such as lambda. The predicted og1e xis
      protein (Xis) is small and very acidic (66 amino acids; pI 4.55), and shows a
      resemblance (32% overall identity) with a putative excisionase encoded by the
      Staphylococcus phage o11. The og1e Int with a deduced molecular mass of 45.5 kDa
      was overproduced in E. coli cells, and electrophoretically analyzed.

PMID- 9034323
TI  - A putative ABC-transport operon of Mycobacterium smegmatis.
AB  - We have recently described the mpr gene of Mycobacterium smegmatis whose product
      confers resistance to mycobacteriophages L5 and D29 when overproduced (Barsom and
      Hatfull (1996) Mol. Microbiol. 21, 159-170). We have determined the nt sequence
      of approximately 3.5 kb immediately adjacent to mpr which appears to encode
      components of an ATP-binding cassette (ABC) transport system. Four closely-spaced
      open reading frames (ORF) were identified although two of these may cooperate to
      produce an integral membrane component of the transport system via a programmed
      translational frameshift. Another putative protein is also predicted to be an
      integral membrane protein, while the third is an ABC-transporter protein. We
      propose that these three putative proteins form a mycobacterial membrane-bound
      complex involved in protein-dependent transport. This is the first ABC-transport
      system to be described in mycobacteria.

PMID- 9034324
TI  - A new hobo, Ac, Tam3 transposable element, hopper, from Bactrocera dorsalis is
      distantly related to hobo and Ac.
AB  - A new transposable element from the hobo, Ac, Tam3 transposon family was isolated
      as a genomic clone from the oriental fruit fly, Bactrocera dorsalis. It is
      approximately 3.1 kb in length with 19-bp inverted terminal repeat sequences
      having a single mismatch. Though sharing several amino acid sequence identities
      with other hAT elements, it is distantly related to both hobo and Ac. Among hAT
      elements thus far described in insects, it is apparently the most distantly
      related to hobo.

PMID- 9034325
TI  - ENP1, an essential gene encoding a nuclear protein that is highly conserved from
      yeast to humans.
AB  - A novel gene in Saccharomyces cerevisiae, ENP1, was found to be essential for
      growth. The ENP1 gene encodes a protein of 483 amino acids (aa). Nucleotide
      sequence analysis revealed that the deduced aa sequence of this gene exhibited
      approx. 60% sequence similarity to the deduced aa sequence of proteins of unknown
      function in Drosophila, Caenorhabditis elegans and humans. No well defined
      functional motifs were evident upon analysis of the aa sequence. The protein was
      found to contain 20% acidic aa residues, with most of them being localized to a
      very negatively charged domain between aa residues 100 and 150. A construct
      encoding a fusion protein consisting of the Enp1 protein fused to the c-myc
      epitope that was either under the control of the ENP1 promoter or the GAL1,10
      promoter was prepared. The construct was used to express the protein tagged with
      the c-myc epitope. Despite the presence of a naturally occurring promoter region
      with homology to the unfolded protein response element, the level of Enp1mycp
      remained unchanged after growth of the cells in the presence of tunicamycin, an
      inhibitor of N-linked glycosylation of proteins. Immunohistochemical studies to
      define the cellular localization of the Enp1myc protein revealed that it was
      localized to the nucleus. Accession No.: U50779.

PMID- 9034326
TI  - Mitochondrial DNA polymerases from yeast to man: a new family of polymerases.
AB  - We report the sequence of a 4.5-kb cDNA clone isolated from a human melanoma
      library which bears high amino acid sequence identity to the yeast mitochondrial
      (mt) DNA polymerase (Mip1p). This cDNA contains a 3720-bp open reading frame
      encoding a predicted 140-kDa polypeptide that is 43% identical to Mip1p. The N
      terminal part of the sequence contains a 13 glutamine stretch encoded by a CAG
      trinucleotide repeat which is not found in the other DNA polymerases gamma (Pol
      gamma). Multiple amino acid sequence alignments with Pol gamma from Saccharomyces
      cerevisiae, Schizosaccharomyces pombe, Pichia pastoris, Drosophila melanogaster,
      Xenopus laevis and Mus musculus show that these DNA polymerases form a family
      strongly conserved from yeast to man and are only loosely related to the Family A
      DNA polymerases.

PMID- 9034327
TI  - Activation of a novel proto-oncogene, Frat1, contributes to progression of mouse
      T-cell lymphomas.
AB  - Acceleration of lymphomagenesis in oncogene-bearing transgenic mice by slow
      transforming retroviruses has proven a valuable tool in identifying cooperating
      oncogenes. We have modified this protocol to search for genes that can
      collaborate effectively with the transgene in later stages of tumor development.
      Propagation of tumors induced by Moloney murine leukemia virus (M-MuLV) in E mu
      Pim1 or H2-K-myc transgenic mice by transplantation to syngeneic hosts permitted
      proviral tagging of 'progression' genes. Molecular cloning of common proviral
      insertion sites that were detected preferentially in transplanted tumors led to
      the identification of a novel gene, designated Frat1. The initial selection for
      integrations near Frat1 occurs in primary tumor cells that have already acquired
      proviruses in other common insertion sites, yielding primary lymphomas that
      contain only a minor fraction of tumor cells with an activated Frat1 allele.
      Transplantation of such primary lymphomas allows for a further expansion of tumor
      cell clones carrying a proviral insertion near Frat1, resulting in detectable
      Frat1 rearrangements in 17% of the transplanted E mu-Pim1 tumors and 30% of the
      transplanted H2-K-myc tumors, respectively. We have cloned and sequenced both the
      mouse Frat1 gene and its human counterpart. The proteins encoded by Frat1 and
      FRAT1 are highly homologous and their functions are thus far unknown. Tumor cell
      lines with high expression of Myc and Pim1 acquired an additional selective
      advantage in vivo upon infection with a Frat1-IRES-lacZ retrovirus, thus
      underscoring the role of Frat1 in tumor progression, and the ability of Frat1 to
      collaborate with Pim1 and Myc in lymphomagenesis.

PMID- 9034328
TI  - Cytoplasmic domains of the common beta-chain of the GM-CSF/IL-3/IL-5 receptors
      that are required for inducing differentiation or clonal suppression in myeloid
      leukaemic cell lines.
AB  - Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that
      controls the production and function of myeloid cells by interaction with a cell
      surface receptor composed of a specific ligand-binding alpha-chain (hGMRalpha)
      and a shared signal-transducing beta-chain (beta c). Co-expression of human GMR
      alpha-chain and wild-type human beta c in two murine leukaemic cell lines (M1 and
      WEHI-3B D+) conferred the ability to terminally differentiate into macrophages
      when stimulated with human GM-CSF. Analysis of cytoplasmic truncation mutants of
      beta c showed that residues to amino acid 783 (numbering from the first amino
      acid of the leader sequence) were sufficient for the GM-CSF-dependent induction
      of all aspects of differentiation in both cell types. However, shorter
      truncations selectively lost, in a cell-specific manner, first the capacity to
      induce macrophage migration in agar and then cell surface differentiation
      antigens and clonal suppression of proliferative potential. The data suggest that
      different aspects of the differentiated phenotype can be dissociated with the
      required signalling pathways originating from distinct regions of the receptor
      cytoplasmic domain and cooperating to produce a fully differentiated macrophage.
      The cooperativity of these pathways and limiting cell signalling intermediate
      pool sizes could explain the observed cell line differences and may have
      implications for normal haemopoiesis.

PMID- 9034329
TI  - Identification of a GDI displacement factor that releases endosomal Rab GTPases
      from Rab-GDI.
AB  - Prenylated Rab GTPases occur in the cytosol in their GDP-bound conformations
      bound to a cytosolic protein termed GDP-dissociation inhibitor (GDI). Rab-GDI
      complexes represent a pool of active, recycling Rab proteins that can deliver
      Rabs to specific and distinct membrane-bound compartments. Rab delivery to
      cellular membranes involves release of GDI, and the membrane-associated Rab
      protein then exchanges its bound GDP for GTP. We report here the identification
      of a novel, membrane-associated protein factor that can release prenylated Rab
      proteins from GDI. This GDI-displacement factor (GDF) is not a guanine nucleotide
      exchange factor because it did not influence the intrinsic rates of nucleotide
      exchange by Rabs 5, 7 or 9. Rather, GDF caused the release of each of these
      endosomal Rabs from GDI, permitting them to exchange nucleotide at their
      intrinsic rates. GDF displayed the greatest catalytic rate enhancement on Rab9
      GDI complexes. However, catalytic rate enhancement paralleled the potency of GDI
      in blocking nucleotide exchange: GDI was shown to be most potent in blocking
      nucleotide exchange by Rab9. The failure of GDF to act on Rab1-GDI complexes
      suggests that it may be specific for endosomal Rab proteins. This novel, membrane
      associated activity may be part of the machinery used to localize Rabs to their
      correct intracellular compartments.

PMID- 9034330
TI  - Tandem SH2 binding sites mediate the RasGAP-RhoGAP interaction: a conformational
      mechanism for SH3 domain regulation.
AB  - Many cellular signaling proteins contain SH3 (Src homology 3) domains that
      mediate protein interactions via specific proline-containing peptides. Unlike SH2
      domains, whose interactions with tyrosine-containing peptides are promoted by
      phosphorylation of the SH2 binding site, the regulatory mechanism for SH3
      interactions is unclear. p120 RasGAP (GTPase-activating protein), which contains
      an SH3 domain flanked by two SH2 domains, forms an abundant SH2-mediated complex
      with p190 RhoGAP in cells expressing activated tyrosine kinases. We have
      identified two closely linked tyrosine-containing peptides in p190 that bind
      simultaneously to the RasGAP SH2 domains upon p190 phosphorylation. This
      interaction is expected to bring the two SH2 domains into close proximity.
      Consequently, RasGAP undergoes a conformational change that results in a 100-fold
      increase in the accessibility of the target binding surface of its SH3 domain.
      These results indicate that the tandem arrangement of SH2 and SH3 domains found
      in a variety of cellular signaling proteins can provide a conformational
      mechanism for regulating SH3-dependent interactions through tyrosine
      phosphorylation. In addition, it appears that the role of p190 in the RasGAP
      signaling complex is to promote additional protein interactions with RasGAP via
      its SH3 domain.

PMID- 9034331
TI  - The mammalian profilin isoforms display complementary affinities for PIP2 and
      proline-rich sequences.
AB  - We present a study on the binding properties of the bovine profilin isoforms to
      both phosphatidylinositol 4,5-bisphosphate (PIP2) and proline-rich peptides
      derived from vasodilator-stimulated phosphoprotein (VASP) and cyclase-associated
      protein (CAP). Using microfiltration, we show that compared with profilin II,
      profilin I has a higher affinity for PIP2. On the other hand, fluorescence
      spectroscopy reveals that proline-rich peptides bind better to profilin II. At
      micromolar concentrations, profilin II dimerizes upon binding to proline-rich
      peptides. Circular dichroism measurements of profilin II reveal a significant
      conformational change in this protein upon binding of the peptide. We show
      further that PIP2 effectively competes for binding of profilin I to poly-L
      proline, since this isoform, but not profilin II, can be eluted from a poly-L
      proline column with PIP2. Using affinity chromatography on either profilin
      isoform, we identified profilin II as the preferred ligand for VASP in bovine
      brain extracts. The complementary affinities of the profilin isoforms for PIP2
      and the proline-rich peptides offer the cell an opportunity to direct actin
      assembly at different subcellular localizations through the same or different
      signal transduction pathways.

PMID- 9034332
TI  - Transgenic expression in the liver of truncated Met blocks apoptosis and permits
      immortalization of hepatocytes.
AB  - Hepatocyte growth factor induces proliferation, motility and differentiation of
      epithelial cells through the tyrosine kinase receptor encoded by the MET
      protooncogene. The cytoplasmic portion of Met (referred to as cyto-Met) is
      activated but only weakly transforming. In order to determine the effect of
      activated Met on hepatocytes, we have targeted truncated Met expression to the
      liver by incorporating the cDNA into a vector carrying the entire human alpha-1
      antitrypsin transcriptional unit. Transgenic expression in the liver of truncated
      human Met, containing the regulatory and the catalytic cytoplasmic domains,
      renders hepatocytes constitutively resistant to apoptosis and reproducibly
      permits immortalization. The emerging stable cell lines are not transformed and
      maintain a highly differentiated phenotype judged by the retention of epithelial
      cell polarity and the expression of hepatocyte-enriched transcription factors as
      well as hepatic products.

PMID- 9034333
TI  - Expression of the papillomavirus E2 protein in HeLa cells leads to apoptosis.
AB  - The papillomavirus E2 protein plays a central role in the viral life cycle as it
      regulates both transcription and replication of the viral genome. In this study,
      we showed that transient expression of bovine papillomavirus type 1 or human
      papillomavirus type 18 (HPV18) E2 proteins in HeLa cells activated the
      transcriptional activity of p53 through at least two pathways. The first one
      involved the binding of E2 to its recognition elements located in the integrated
      viral P105 promoter. E2 binding consequently repressed transcription of the
      endogenous HPV18 E6 oncogene, whose product has been shown previously to promote
      p53 degradation. The second pathway did not require specific DNA binding by E2.
      Expression of E2 induced drastic physiological changes, as evidenced by a high
      level of cell death by apoptosis and G1 arrest. Overexpression of a p53 trans
      dominant-negative mutant abolished both E2-induced p53 transcriptional activation
      and E2-mediated G1 growth arrest, but showed no effect on E2-triggered apoptosis.
      These results suggest that the effects of E2 on cell cycle progression and cell
      death follow distinct pathways involving two different functions of p53.

PMID- 9034334
TI  - D-mef2 is a target for Tinman activation during Drosophila heart development.
AB  - The NK-type homeobox gene tinman and the MADS box gene D-mef2 encode
      transcription factors required for the development and differentiation of the
      Drosophila heart, and closely related genes regulate cardiogenesis in
      vertebrates. Genetic analyses indicate that tinman and D-mef2 act at early and
      late steps, respectively, in the cardiogenic lineage. However, it is unknown
      whether regulatory interactions exist between these developmental control genes.
      We show that D-mef2 expression in the developing Drosophila heart requires a
      novel upstream enhancer containing two Tinman binding sites, both of which are
      essential for enhancer function in cardiac muscle cells. Transcriptional activity
      of this cardiac enhancer is dependent on tinman function, and ectopic Tinman
      expression activates the enhancer outside the cardiac lineage. These results
      define the only known in vivo target for transcriptional activation by Tinman and
      demonstrate that D-mef2 lies directly downstream of tinman in the genetic cascade
      controlling heart formation in Drosophila.

PMID- 9034335
TI  - Yeast telomeric sequences function as chromosomal anchorage points in vivo.
AB  - Site-specific recombination in Saccharomyces cerevisiae was used to generate non
      replicative DNA rings containing yeast telomeric sequences. In topoisomerase
      mutants expressing Escherichia coli topoisomerase I, the rings adopted a novel
      DNA topology consistent with the ability of yeast telomeric DNA to block or
      retard the axial rotation of DNA. DNA fragments bearing portions of the terminal
      repeat sequence C1-3 A/TG1-3 were both necessary and sufficient to create a
      barrier to DNA rotation. Synthetic oligonucleotide sequences containing Rap1p
      binding sites, a well represented motif in naturally occurring C1-3A arrays, also
      conferred immobilization; mutant Rap1p binding sites and telomeric sequences from
      other organisms were not sufficient. DNA anchoring was diminished by addition of
      competing telomeric sequences, implicating a role for an as yet unidentified
      limiting trans-acting factor. Though Rap1p is a likely protein constituent of the
      DNA anchor, deletion of the non-essential C-terminal domain did not affect the
      topology of telomeric DNA rings. Similarly, disruption of SIR2, SIR3 and SIR4,
      genes which influence a variety of telomere functions in yeast, also had no
      effect. We propose that telomeric DNA supports the formation of a SIR-independent
      macromolecular protein-DNA assembly that hinders the motion of DNA because of its
      linkage to an insoluble nuclear structure. Potential roles for DNA anchoring in
      telomere biology are discussed.

PMID- 9034336
TI  - Fission yeast pheromone blocks S-phase by inhibiting the G1 cyclin B-p34cdc2
      kinase.
AB  - Yeast pheromones block cell cycle progression in G1 in order to prepare mating
      partners for conjugation. We have investigated the mechanism underlying pheromone
      induced G1 arrest in the fission yeast Schizosaccharomyces pombe. We find that
      the G1-specific transcription factor p65cdc10-p72res1/sct1 which controls the
      expression of S-phase genes is fully activated in pheromone, unlike the analogous
      control in budding yeast. In contrast, the G1 function of p34cdc2 acting after
      activation of the G1-specific transcription is blocked. Pheromone inhibits the
      p34cdc2 kinase associated with both the G1-specific B-type cyclin p45cig2 and the
      B-type cyclin p56cdc13 and overexpression of p45cig2 or p47cdc13delta90 overcomes
      the pheromone-induced G1 arrest. G1 arrest is compromised in enlarged cells. We
      suggest that onset of S-phase is controlled by pheromone inhibiting the B-cyclin
      associated kinase in G1, and that increasing cell size contributes to the
      mechanism for pheromone adaptation. Thus, pheromone in fission and budding yeast
      acts similarly in inhibiting the G1 cyclin-dependent kinase (CDK), but differs in
      its effects on the G1/S transcriptional control, suggesting that inhibition of
      CDKs may be a more general mechanism for the control of G1 progression compared
      with G1/S transcriptional control.

PMID- 9034337
TI  - Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15
      phosphorylation.
AB  - The G2 DNA damage checkpoint ensures maintenance of cell viability by delaying
      progression into mitosis in cells which have suffered genomic damage. It is
      controlled by a number of proteins which are hypothesized to transduce signals
      through cell cycle regulators to delay activation of p34cdc2. Studies in
      mammalian cells have correlated induction of inhibitory tyrosine 15 (Y15)
      phosphorylation on p34cdc2 with the response to DNA damage. However, genetic
      studies in fission yeast have suggested that the major Y15 kinase, p107wee1, is
      not required for the cell cycle delay in response to DNA damage, although it is
      required for survival after irradiation. Thus, the target of the checkpoint, and
      hence the mechanism of cell cycle delay, remains unknown. We show here that Y15
      phosphorylation is maintained in checkpoint-arrested fission yeast cells.
      Further, wee1 is required for cell cycle arrest induced by up-regulation of an
      essential component of this checkpoint, chk1. We observed that p107wee1 is
      hyperphosphorylated in cells delayed by chk1 overexpression or UV irradiation,
      and that p56chk1 can phosphorylate p107wee1 directly in vitro. These observations
      suggest that in response to DNA damage p107wee1 is phosphorylated by p56chk1 in
      vivo, and this results in maintenance of Y15 phosphorylation and hence G2 delay.
      In the absence of wee1, other Y15 kinases, such as p66mik1, may partially
      substitute for p107wee1 to induce cell cycle delay, but this wee1-independent
      delay is insufficient to maintain full viability. This study establishes a link
      between a G2 DNA damage checkpoint function and a core cell cycle regulator.

PMID- 9034338
TI  - Histone acetyltransferase activity and interaction with ADA2 are critical for
      GCN5 function in vivo.
AB  - Yeast GCN5 is one component of a putative adaptor complex that includes ADA2 and
      ADA3 and functionally connects DNA-bound transcriptional activators with general
      transcription factors. GCN5 possesses histone acetyltransferase (HAT) activity,
      conceptually linking transcriptional activation with enzymatic modification at
      chromatin. We have identified the minimal catalytic domain within GCN5 necessary
      to confer HAT activity and have shown that in vivo activity of GCN5 requires this
      domain. However, complementation of growth and transcriptional activation in gcn5
      cells required not only the HAT domain of GCN5, but also interaction with ADA2.
      The bromodomain in GCN5 was dispensable for HAT activity and for transcriptional
      activation by strong activators; however, it was required for full
      complementation in other assays. Fusion of GCN5 to the bacterial lexA DNA binding
      domain activated transcription in vivo, and required both the HAT domain and the
      ADA2 interaction domain. These results suggest that both functions of GCN5, HAT
      activity and interaction with ADA2, are necessary for targeting and acetylation
      of nucleosomal histones.

PMID- 9034339
TI  - A novel ubiquitin-specific protease is dynamically associated with the PML
      nuclear domain and binds to a herpesvirus regulatory protein.
AB  - Herpes simplex virus type 1 immediate-early protein Vmw110 is a non-specific
      activator of gene expression and is required for efficient initiation of the
      viral lytic cycle. Since Vmw110-deficient viruses reactivate inefficiently in
      mouse latency models it has been suggested that Vmw110 plays a role in the
      balance between the latent and lytic states of the virus. The mechanisms by which
      Vmw110 achieves these functions are poorly understood. Vmw110 migrates to
      discrete nuclear structures (ND10) which contain the cellular PML protein, and in
      consequence PML and other constituent proteins are dispersed. In addition, Vmw110
      binds to a cellular protein of approximately 135 kDa, and its interactions with
      the 135 kDa protein and ND10 contribute to its ability to stimulate gene
      expression and viral lytic growth. In this report we identify the 135 kDa protein
      as a novel member of the ubiquitin-specific protease family. The protease is
      distributed in the nucleus in a micropunctate pattern with a limited number of
      larger discrete foci, some of which co-localize with PML in ND10. At early times
      of virus infection, the presence of Vmw110 increases the proportion of ND10 which
      contain the ubiquitin-specific protease. These results identify a novel,
      transitory component of ND10 and implicate a previously uncharacterized ubiquitin
      dependent pathway in the control of viral gene expression.

PMID- 9034340
TI  - The paramyxovirus, Sendai virus, V protein encodes a luxury function required for
      viral pathogenesis.
AB  - The Sendai virus (SeV) V protein is characterized by the unique cysteine-rich
      domain in its carboxy-terminal half which is fused to the amino-terminal half of
      the P protein, but its function has remained enigmatic. The V protein-directing
      mRNA is generated by a remarkable process known as mRNA editing involving the
      pseudotemplated addition of a single G residue at a specific septinucleotide
      locus in the P gene, whereas the unedited exact copy encodes the P protein. Here,
      we introduced two nucleotide changes in the septinucleotide motif (UUUUCCC to
      UUCUUCC) in a full-length SeV cDNA and were able to recover a virus from the
      cDNA, which was devoid of mRNA editing and hence unable to synthesize the V
      protein. Compared with the parental wild-type virus with regard to gene
      expression, replication and cytopathogenicity in various cell lines in vitro, the
      V(-) virus was found to be either potentiated or comparable but never attenuated.
      The V(-) virus, however, showed markedly attenuated in vivo replication capacity
      in and pathogenicity for mice. Thus, though categorized as a nonessential gene
      product, SeV V protein encodes a luxury function required for in vivo
      pathogenicity.

PMID- 9034342
TI  - Viroid processing: switch from cleavage to ligation is driven by a change from a
      tetraloop to a loop E conformation.
AB  - A longer-than-unit-length transcript of potato spindle tuber viroid is correctly
      processed in a potato nuclear extract only if the central conserved region is
      folded into a multi-helix junction containing at least one GNRA tetraloop
      hairpin. The cleavage-ligation site between G95 and G96 was mapped with S1
      nuclease and primer extension. The structural motifs involved in the processing
      mechanism were analysed by UV crosslinking, chemical mapping, phylogenetic
      comparison and thermodynamic calculations. For processing, the first cleavage
      occurs within the stem of the GNRA tetraloop; a local conformational change
      switches the tetraloop motif into a loop E motif, stabilizing a base-paired 5'
      end. The second cleavage yields unit-length linear intermediates, whose 3' end is
      also base-paired and most probably coaxially stacked in optimum juxtaposition to
      the 5' end. They are ligated to mature circles autocatalytically, with low
      efficiency, or enzymatically, with high efficiency.

PMID- 9034341
TI  - Concerted evolution of the tandemly repeated genes encoding human U2 snRNA (the
      RNU2 locus) involves rapid intrachromosomal homogenization and rare
      interchromosomal gene conversion.
AB  - We have surveyed the tandemly repeated genes encoding U2 snRNA in a diverse panel
      of humans. We found only two polymorphisms within the U2 repeat unit: a SacI
      polymorphism (alleles SacI+ or SacI-) and a CT microsatellite polymorphism
      (alleles CT+ or CT-). Surprisingly, individual U2 tandem arrays are entirely
      SacI+ or SacI-, and entirely CT+ or CT-, although the SacI and CT alleles can
      occur in any combination. We also found that polymorphisms in the left and right
      junction regions flanking the tandem array fall into only two haplotypes (JL+ and
      JL-, JR+ and JR-). Most surprisingly, JL+ is always associated with JR+, and JL-
      with JR-. Thus individual U2 arrays do not exchange flanking markers, despite
      independent assortment and subsequent homogenization of the SacI and CT alleles
      within the U2 repeat units. We propose that the primary driving force for
      concerted evolution of the tandem U2 genes is intrachromosomal homogenization;
      interchromosomal genetic exchanges are much rarer, and reciprocal nonsister
      chromatid exchange apparently does not occur. Thus concerted evolution of the U2
      tandem array occurs in situ along a chromosome lineage, and linkage
      disequilibrium between sequences flanking the U2 array may persist for long
      periods of time.

PMID- 9034343
TI  - Oncogenic potential of TAR RNA binding protein TRBP and its regulatory
      interaction with RNA-dependent protein kinase PKR.
AB  - TAR RNA binding protein (TRBP) belongs to an RNA binding protein family that
      includes the double-stranded RNA-activated protein kinase (PKR), Drosophila
      Staufen and Xenopus xlrbpa. One member of this family, PKR, is a serine/threonine
      kinase which has anti-viral and anti-proliferative effects. In this study we show
      that TRBP is a cellular down-regulator of PKR function. Assaying expression from
      an infectious HIV-1 molecular clone, we found that PKR inhibited viral protein
      synthesis and that over-expression of TRBP effectively countered this inhibition.
      In intracellular and in cell-free assays we show that TRBP directly inhibits PKR
      autophosphorylation through an RNA binding-independent pathway. Biologically,
      TRBP serves a growth-promoting role; cells that overexpress TRBP exhibit
      transformed phenotypes. Our results demonstrate the oncogenic potential of TRBP
      and are consistent with the notion that intracellular PKR function contributes
      physiologically towards regulating cellular proliferation.

PMID- 9034344
TI  - Open complex formation around a lesion during nucleotide excision repair provides
      a structure for cleavage by human XPG protein.
AB  - Human XPG nuclease makes the 3' incision during nucleotide excision repair of
      DNA. The enzyme cleaves model DNA bubble structures specifically near the
      junction of unpaired DNA with a duplex region. It is not yet known, however,
      whether an unpaired structure is an intermediate during actual DNA repair. We
      find here that XPG requires opening of >5 bp for efficient cleavage. To seek
      direct evidence for formation of an open structure around a lesion in DNA during
      a nucleotide excision repair reaction in vitro, KMnO4 footprinting experiments
      were performed on a damaged DNA molecule bearing a uniquely placed cisplatin
      adduct. An unwound open complex spanning approximately 25 nucleotides was
      observed that extended to the positions of 5' and 3' incision sites and was
      dependent on XPA protein and on ATP. Opening during repair occurred prior to
      strand incision by XPG.

PMID- 9034345
TI  - A role for DNA primase in coupling DNA replication to DNA damage response.
AB  - The temperature-sensitive yeast DNA primase mutant pri1-M4 fails to execute an
      early step of DNA replication and exhibits a dominant, allele-specific
      sensitivity to DNA-damaging agents. pri1-M4 is defective in slowing down the rate
      of S phase progression and partially delaying the G1-S transition in response to
      DNA damage. Conversely, the G2 DNA damage response and the S-M checkpoint
      coupling completion of DNA replication to mitosis are unaffected. The signal
      transduction pathway leading to Rad53p phosphorylation induced by DNA damage is
      proficient in pri1-M4, and cell cycle delay caused by Rad53p overexpression is
      counteracted by the pri1-M4 mutation. Altogether, our results suggest that DNA
      primase plays an essential role in a subset of the Rad53p-dependent checkpoint
      pathways controlling cell cycle progression in response to DNA damage.

PMID- 9034346
TI  - Both the isomerase and chaperone activities of protein disulfide isomerase are
      required for the reactivation of reduced and denatured acidic phospholipase A2.
AB  - The spontaneous reactivation yield of acidic phospholipase A2 (APLA2), a protein
      containing seven disulfide bonds, after reduction and denaturation in guanidine
      hydrochloride is very low. Protein disulfide isomerase (PDI) markedly increases
      the reactivation yield and prevents the aggregation of APLA2 during refolding in
      a redox buffer containing GSH and GSSG. S-methylated PDI (mPDI), with no
      isomerase but as nearly full chaperone activity as native PDI, has no effect on
      either the reactivation or aggregation of APLA2. However, the simultaneous
      presence of PDI and mPDI in molar ratios to APLA2 of 0.1 and 0.9 respectively
      fully reactivates the denatured enzyme, as does PDI alone at a ratio of 1. At
      ratios of 0.1 and 0.15 respectively, they completely suppress APLA2 aggregation,
      as does PDI alone at a ratio of 0.25. Moreover, delayed addition of PDI to the
      refolding buffer greatly diminished the reactivation yield of APLA2, but this
      deteriorating effect can be alleviated markedly by the presence of mPDI in the
      refolding buffer. Without GSSG, mPDI prevents the aggregation of APLA2 during
      refolding. It is proposed that the in vitro action of PDI as a foldase consists
      of both isomerase and chaperone activities, and the latter activity can be fully
      replaced by mPDI.

PMID- 9034348
TI  - Change in fat-free mass assessed by bioelectrical impedance, total body potassium
      and dual energy X-ray absorptiometry during prolonged weight loss.
AB  - A total of 16 obese women (body mass index (BMI) 30-43 kg m(-2)) participated in
      a weight reduction study. Before and after a weight loss of 11.7 +/- 7.4 kg (mean
      +/- SD), body composition was assessed by dual energy X-ray absorptiometry (DXA),
      and total body potassium counting (TBK). These measurements were compared with
      bioimpedance analysis (BIA) by applying 11 predictive BIA equations published in
      the literature. Predictive equations for the present study population were
      developed, with the use of fat-free mass (FFM) as assessed by TBK and DXA as
      references in multiple regression analysis. The results of the BIA equations
      varied widely; FFM was generally overestimated by BIA as compared with DXA and
      TBK before and after weight loss. During weight loss, the FFM did not change, as
      estimated by DXA (1.3 +/- 2.3 kg, p > 0.05) and TBK (0.9 +/- 2.9 kg, p > 0.05).
      The recorded change in impedance (R) was also insignificant. Three BIA equations
      from the literature, which were not specific for the degree of obesity in the
      present study group, predicted changes in FFM (from 0.5 + 3.6 to 2.4 +/- 4.4kg, p
      > 0.05) that were comparable with those estimated by the reference methods. Eight
      equations from the literature, which included equations specific for the degree
      of obesity in the study group, and the group specific equations developed for the
      present population predicted significant changes in FFM during weight loss (from
      2.3 +/- 3.0 to 5.0 +/- 3.0 kg, p < 0.05). We conclude that in obesity most
      predictive equations are unable to predict static body composition and are not
      reproducible for individuals over time. However, a significant or insignificant
      change in R (without accompanying predictive equations) may be used to indicate
      whether FFM is lost or preserved in groups of obese subjects.

PMID- 9034347
TI  - A small heat shock protein stably binds heat-denatured model substrates and can
      maintain a substrate in a folding-competent state.
AB  - The small heat shock proteins (sHSPs) recently have been reported to have
      molecular chaperone activity in vitro; however, the mechanism of this activity is
      poorly defined. We found that HSP18.1, a dodecameric sHSP from pea, prevented the
      aggregation of malate dehydrogenase (MDH) and glyceraldehyde-3-phosphate
      dehydrogenase heated to 45 degrees C. Under conditions in which HSP18.1 prevented
      aggregation of substrates, size-exclusion chromatography and electron microscopy
      revealed that denatured substrates coated the HSP18.1 dodecamers to form expanded
      complexes. SDS-PAGE of isolated complexes demonstrated that each HSP18.1
      dodecamer can bind the equivalent of 12 MDH monomers, indicating that HSP18.1 has
      a large capacity for non-native substrates compared with other known molecular
      chaperones. Photoincorporation of the hydrophobic probe 1,1'-bi(4
      anilino)naphthalene-5,5'-disulfonic acid (bis-ANS) into a conserved C-terminal
      region of HSP18.1 increased reversibly with increasing temperature, but was
      blocked by prior binding of MDH, suggesting that bis-ANS incorporates proximal to
      substrate binding regions and that substrate-HSP18.1 interactions are
      hydrophobic. We also show that heat-denatured firefly luciferase bound to
      HSP18.1, in contrast to heat-aggregated luciferase, can be reactivated in the
      presence of rabbit reticulocyte or wheat germ extracts in an ATP-dependent
      process. These data support a model in which sHSPs prevent protein aggregation
      and facilitate substrate refolding in conjunction with other molecular
      chaperones.

PMID- 9034349
TI  - Characterization and determinants of an electronegatively charged low-density
      lipoprotein in human plasma.
AB  - There is evidence that oxidative modification of low density lipoprotein (LDL) is
      an important step in the atherosclerotic process. Electronegatively charged LDL
      has been found in the atherosclerotic lesions of rabbit and human and it is
      supposed to represent an early modification of LDL in the oxidative process in
      vivo. We describe a chromatographic method for determination of an LDL
      subfraction (LDL-) percentage from plasma LDL and the investigation of the lipid
      composition of native LDL and LDL- fractions separated by this method. We also
      studied the main determinants of the change in plasma LDL- level in a population
      sample of 45 men during a 6-months follow-up period. The LDL- fraction separated
      by anion-exchange chromatography had significantly higher triglyceride and free
      cholesterol and significantly lower phospholipid and total cholesterol contents,
      and lower alpha-tocopherol to triglyceride ratio than native LDL. In a 6-month
      follow up of 45 subjects, decreases in the ratio of blood glutathione disulphide
      to reduced glutathione, in serum LDL cholesterol and in serum n-3 polyunsaturated
      fatty acids, and an increase in plasma beta-carotene concentration had
      independent associations with a decrease of LDL-. The linear regression model
      including only these four variables was able to account for 47% of the variation
      of LDL-. Our findings suggest that the change in the plasma LDL- percentage
      measured by an anion-exchange liquid chromatography is predicted by changes in
      the major determinants of lipid peroxidation.

PMID- 9034350
TI  - Analysis of proteinuria: reference limits for urine excretion of albumin, protein
      HC, immunoglobulin G, kappa- and lambda-immunoreactivity, orosomucoid and alpha 1
      antitrypsin.
AB  - Efficient use of assessment of urine protein excretion in nephrological practice
      requires adequate reference intervals. To determine the upper reference limits of
      urine albumin, protein HC (alpha 1-microglobulin, immunoglobulin G (IgG),
      orosomucoid (alpha 1-acid glycoprotein, alpha 1-antitrypsin, and kappa- and
      lambda-chain immunoreactivities, the concentrations of these proteins were
      measured in urine samples from 95 healthy, adult individuals, using rapid,
      generally available methods and with conditions for urine collection which
      secured stable protein levels. The obtained values were expressed in mg 1(-1), as
      the urine protein-creatinine index and as fractional protein-creatinine
      clearance. No differences were found between the upper reference limits in the
      first voided morning urine samples and the randomly collected urine samples, nor
      between the upper reference limits in urine samples collected from males and
      females. The urinary excretion of the tested proteins did not correlate to age,
      positive dipsticks for haematuria nor to granular casts in urine sediment. Thus,
      the same upper reference limits can be used for both sexes and regardless of the
      type of urine collection. The upper reference limits of urine protein-creatinine
      index found in this study were: for albumin, 3.8 mg mmol(-1); for protein HC, 0.7
      mg mmol; for IgG, 0.8 mg mmol(-1); for orosomucoid, 0.7 mg mmol(-1); for alpha 1
      antitrypsin, 0.2 mg mmol(-1), and for kappa-immunoreactivity 0.7 mg mmol(-1). The
      upper reference limit for lambda-immunoreactivity was below the detection limit.

PMID- 9034351
TI  - Cardiac markers in the early hours of acute myocardial infarction: clinical
      performance of creatine kinase, creatine kinase MB isoenzyme (activity and mass
      concentration), creatine kinase MM and MB subform ratios, myoglobin and cardiac
      troponin T.
AB  - We compared early markers of acute myocardial infarction (AMI) in the first 6 h
      from the onset of symptoms in 133 non-traumatized patients arriving at the
      emergency department with chest pain suggestive of AMI. Clinical performance
      parameters were calculated on the basis of 45 patients with AMI and 88 patients
      with a non-AMI diagnosis. At admission and in the first 0-3 h after the onset of
      chest pain the creatine kinase-MB (CK-MB) subform ratio was the most sensitive
      test at a comparable specificity level of 0.95. In the time interval of 3-5 h,
      myoglobin, the CK-MB mass concentration and the CK-MB subform ratio were
      associated with the greatest areas under receiver operating characteristic (ROC)
      curves, but differences between these tests were small and non-significant. At 6
      h from the onset of pain, differences in clinical performance between the same
      three tests were even smaller whether or not samples drawn after the start of
      thrombolytic treatment were included in the test comparison. For confirmation of
      AMI at 6 h after onset of pain, CK-MB (activity and mass concentration)
      demonstrated the highest positive likelihood ratio, and for exclusion of AMI at 6
      h the CK-MB subform ratio was associated with the highest negative likelihood
      ratio. However, differences between the CK-MB subform ratio, CK-MB mass
      concentration and myoglobin were not significant as estimated by the substantial
      overlap between the confidence intervals of the likelihood ratios and the ROC
      areas at 6 h. Cardiac troponin T (cTnT) demonstrated an ROC area equal to the CK
      MB isoform ratio and myoglobin at 6 h. However, the likelihood ratio for ruling
      out AMI was lower, mostly due to the elevated cTnT in unstable coronary disease
      not defined as AMI. We conclude that the CK-MB subform ratio, CK-MB mass
      concentration and myoglobin do not demonstrate any significant differences in
      clinical performance for ruling in or ruling out acute myocardial infarction at 6
      h after the onset of chest pain.

PMID- 9034352
TI  - Urinary immunoreactive deoxypyridinoline in children and adolescents: variations
      with age, sex and growth velocity.
AB  - The collagen cross-linking compound deoxypyridinoline (DPD) has been shown to be
      a marker of bone resorption and skeletal growth in children. However, the
      original method for the determination of total (i.e. free and peptide-bound) DPD
      (tDPD) in urine samples is technically demanding. The recent development of a
      simple enzyme-linked immunosorbent assay for the quantification of immunogenic
      DPD (iDPD) in urine samples might be a more convenient technique. Yet, it is
      unclear at present whether iDPD is equal to tDPD as an index of bone resorption
      and skeletal growth. Therefore, using 24-h urines from 144 healthy children and
      adolescents aged 4-19 years, we established reference ranges for the daily
      urinary excretion of iDPD. A close correlation was found between the daily
      urinary excretion of iDPD and tDPD related to body weight (r = 0.87, p < 0.001).
      In 72 subjects aged 4-18 years, the daily excretion of iDPD normalized to body
      weight was highly significantly correlated with growth velocity (r = 0.70, p <
      0.001). We conclude that the enzyme-linked immunosorbent assay for urinary iDPD
      appears to provide a good index of bone resorption and growth in healthy
      children.

PMID- 9034353
TI  - Cardiopulmonary bypass causes release of leukocyte proteinase-3.
AB  - Activation of leukocytes is an important but not fully understood event during
      cardiopulmonary bypass. Leukocyte proteinase-3, also known as neutrophil
      proteinase-4, was analysed in plasma by means of an enzyme-linked immunosorbent
      assay after heart surgery with extracorporeal circulation. The levels of
      proteinase-3 increased ninefold after surgery compared with preoperative values.
      Over the following days, the levels declined but were still elevated on the
      second postoperative day. The levels of proteinase-3 3 h after heart surgery were
      correlated to the time on cardiopulmonary bypass. Proteinase-3 is involved in the
      inflammatory process seen after extracorporeal circulation.

PMID- 9034354
TI  - Significance of IgG for the activity of factor XII measured in human plasma.
AB  - The plasma level of factor XII (FXII) was measured in samples from healthy young
      men. The activated contact factor was assayed as prekallikrein activator (PKA),
      as S-2222 amidase, and in radial immunodiffusion tests. By removing the bulk of
      IgG on protein G columns before the activation procedure, the functional
      activities increased to about 135%. In such test preparations, PAGE immunoblot
      experiments with polyclonal antibodies against FXII showed, in addition to FXIIa
      (80 kD), a double band with a molecular weight of about 46 kD. This protein could
      also be detected with a light-chain-specific monoclonal antibody to FXII, but not
      with such an antibody directed against its heavy chain. The 46-kD band was also
      observed in plasma deficient in FXII. The amidase assays indicated that the minor
      part of FXIIa was present in some kind of association with another protease. To
      obtain a correct estimation of total FXIIa in the amidase assays a sufficiently
      high level of FXI was required compared to that of FXII. The PKA assays were
      generally carried out with a prekallikrein (PK) substrate containing IgG. By
      replacing this substrate by PK free from IgG additional PKA activity was
      observed, the activity appearing also in plasma deficient in FXII.

PMID- 9034355
TI  - Preanalytical phase in coagulation testing: state of the art in the laboratories
      of the Piedmont region, Italy.
AB  - The control of preanalytical variables is critical, particularly for coagulation
      assays, since this has a direct influence on the quality of results and on their
      clinical reliability. The aim of the study was to evaluate the extent of
      information about preanalysis in the laboratories of a large region of northern
      Italy that perform tests of haemostasis. A questionnaire was sent concerning the
      number of coagulation analyses per year, the system of blood drawing, the
      anticoagulants and the tubes in use, the amount of blood collected, the tendency
      to reject unsuitable specimens, the storage temperatures, the times between
      collection and analysis, the conditions of tube centrifugation and
      identification, and the presence of staff specifically occupied in coagulation
      testing. Complete answers were offered by 136 laboratories (81%; 69 private and
      67 public) that reported a total amount of 3,648,000 determinations per year.
      Statistical analysis was carried out on the findings of the investigation, in
      order to assess their significance and to detect possible correlations between
      the variables under consideration. The results show significant attention being
      given by laboratories to the preanalytical phase. This is also indicated by the
      large percentage of complete answers obtained. Some of the important positive
      aspects shown in the study are: (1) the preference for the closed system for
      blood sampling; (2) the prevalent use of primary tubes for testing; (3) a strong
      tendency to reject incorrect samples for analysis. On the other hand, a major
      problem seems to lie in the delay, particularly in some big centres, in
      processing of specimens, which can be critical for the correct performance of
      coagulation assays. The data obtained reflect with good reliability the overall
      situation in coagulation-testing laboratories in northern Italy.

PMID- 9034356
TI  - Processing of human mitochondrial tRNA(Ser(AGY))GCU: a novel pathway in tRNA
      biosynthesis.
AB  - The 5' end of mature tRNAs is formed by the endonucleolytic removal of a leader
      sequence. RNase P, the enzyme generally responsible for this event, makes use of
      structural information contained within the tRNA domain of the precursor to
      recognize substrates and direct cleavage to the tRNA's 5' end. Human
      mitochondrial tRNA(Ser(AGY)GCU, a tRNA that , a tRNA that shows several
      structural deviations from "classical" as well as mitochondrial tRNAs, the most
      prominent of which is the lack of a D domain, is processed at its 5' end via a
      novel, "non-RNase P" pathway. 5' end maturation of tRNA(Ser(AGY)GCU is the
      consequence of 3' end processing of the abutting tRNA(His), precisely flanking
      the tRNA(Ser(AGY)GCU gene at its 5' end. Deletion of this adjoining tRNA
      structure abolishes efficient 5' end maturation of tRNA(Ser(AGY)GCU in vitro,
      suggesting that the human mitochondrial tRNA(SeR(AGY)GCU employs a 5'abutting
      tRNA as a processing signal for 5' end maturation in a kind of molecular
      commensalism.

PMID- 9034357
TI  - Rapid evolution of translational control mechanisms in RNA genomes.
AB  - We have introduced 13 base substitutions into the coat protein gene of RNA
      bacteriophage MS2. The mutations, which are clustered ahead of the overlapping
      lysis cistron, do not change the amino acid sequence of the coat protein, but
      they disrupt a local hairpin, which is needed to control translation of the lysis
      gene. The mutations decreased the phage titer by four orders of magnitude but,
      upon passaging, the virus accumulated suppressor mutations that raised the
      fitness to almost wild-type level. Analysis of the pseudorevertants showed that
      the disruption of the local hairpin, controlling expression of the lysis gene,
      had apparently been so complete that its restoration by chance mutations could
      not be achieved. Instead, alternative foldings initiated by the starting
      mutations were further stabilized and optimized. Strikingly, in the
      pseudorevertants analyzed, translational control of the lysis gene had been
      restored. This feat was accomplished by, on average, four suppressor mutations
      that generally occurred at codon wobble positions. We also introduced 11
      mutations in a hairpin more upstream in the coat protein gene and not implicated
      in lysis control. Here the titer dropped by three logs, but pseudorevertants with
      a fitness close to wild-type were soon generated. These pseudorevertants again
      were the result of the optimization of alternative foldings induced by the
      mutations. The transition of the secondary structure from wild-type to
      pseudorevertant could be visualized by structure probing. Our study shows that
      the folding of the RNA is an important phenotypic property of RNA viruses.
      However, its distortion can easily be overcome by optimizing alternative base
      pairings. These new structures are not qualitatively equivalent to the original
      one, since they do not successfully compete with the wild-type.

PMID- 9034358
TI  - Role of the spacer boxA of Escherichia coli ribosomal RNA operons in efficient 23
      S rRNA synthesis in vivo.
AB  - A boxA sequence, known to be important for transcriptional antitermination, is
      found in both the leader region and in the spacer between the 16 S and 23 S genes
      of Escherichia coli ribosomal RNA operons. We have shown that a functional leader
      boxA is important for efficient completion of 16 S rRNA transcription. In this
      study, point mutations were introduced into the 16S-23S spacer boxA of a plasmid
      encoded E. coli rrnB operon in order to study the contribution of this conserved
      sequence element to ribosomal RNA synthesis in vivo. The rrnB mutant constructs
      contained an additional point mutation in each of the 16 S and 23 S genes, which
      were used to distinguish rRNA derived from plasmid and chromosomal rrn operons by
      primer extension analysis. Mutations in the spacer boxA reduced the proportion of
      plasmid-derived 23 S rRNA without affecting synthesis of plasmid-derived 16 S
      rRNA or spacer boxA RNA, indicating that premature termination of transcription
      occurred during 23 S rRNA synthesis. Reductions in plasmid-derived 23 S rRNA were
      very similar for total cellular RNA, 50 S subunits and 70 S ribosomes, suggesting
      that plasmid-derived rRNAs from mutant operons were functional in ribosome
      biogenesis. In the presence of a wild-type leader boxA, single nucleotide
      exchanges in the spacer boxA reduced the proportion of plasmid-derived 23 S rRNA
      from 70% to about 55% under conditions of exponential growth in rich medium. This
      proportion further decreased to 20 to 25% with an additional point mutation in
      the leader boxA. We conclude that modification of RNA polymerase into a
      termination-resistant form has to be renewed at the spacer boxA in order to
      ensure the faithful completion of full-length 23 S rRNA.

PMID- 9034359
TI  - An approximately half set of histone genes is enough for cell proliferation and a
      lack of several histone variants causes protein pattern changes in the DT40
      chicken B cell line.
AB  - Of the 44 chicken histone genes, 39 are located in a major histone gene cluster
      of 110 kb, the others residing in four separate regions. The 42 sequenced genes
      encode six H1 variants, three H2A variants, four H2B variants, two H3 variants,
      and one histone H4. To clarify the influence on cell functions of simultaneous
      deletion of an approximately half set of the genes and some of the variants, we
      generated homozygous chicken DT40 mutants by disruption of two allelic segments
      of 57 kb, containing the 21 genes, using gene targeting techniques. Analyses with
      antisense RNA probes common or specific for gene families H1, H2A, H2B, H3 and H4
      indicated that the remaining members of each of the gene families were expressed
      more in the mutants than in DT40 cells, resulting in maintenance of constant
      steady-state levels of mRNAs. Two-dimensional polyacrylamide gel electrophoresis
      showed that in the mutants several cellular proteins newly appeared or increased,
      and some other proteins disappeared or decreased quantitatively. These results
      demonstrate that all the histone gene families have the inherent ability to
      compensate for the disruption of a fair number of their own constituents.
      Furthermore, some of the histone variants are involved in regulation of the
      expression of putative genes that encode the proteins that varied in mutant DT40
      cells, this participation is not compensated for by any residual variant of the
      same histone subtype(s).

PMID- 9034360
TI  - Three-dimensional structure of NADH-dehydrogenase from Neurospora crassa by
      electron microscopy and conical tilt reconstruction.
AB  - NADH-dehydrogenase (Complex I) is the first complex of the mitochondrial
      respiratory chain. It is an amphipatic molecule located in the inner
      mitochondrial membrane and is composed of at least 35 unique subunits encoded by
      both mitochondrial and nuclear DNA. The whole complex was isolated in detergent
      from the fungus Neurospora crassa. It is very stable in its isolated form and was
      analysed as such by electron microscopy. Its mass, determined by dark-field
      scanning electron microscopy was estimated as 1.12 MDa. The complex was imaged by
      transmission electron microscopy, by negative staining and by cryo-electron
      microscopy. A three-dimensional model, with a resolution estimated at 35 A, was
      calculated from images of negatively stained complexes by the random conical tilt
      reconstruction technique. This model confirms the general L-shape of the
      molecule, with arms of equal length and corroborates the hypothesis of a
      subdivision of the whole complex into three functional domains. Immuno-labelling
      of the 49 kDA subunit of the peripheral arm allowed its localization within the
      complex. This is a first step in the subunit mapping of Complex I and the
      understanding of its activity.

PMID- 9034361
TI  - Effects of mutations in Pr160gag-pol upon tRNA(Lys3) and Pr160gag-plo
      incorporation into HIV-1.
AB  - During HIV-1 viral assembly, both Pr160gag-pol and primer tRNA(Lys3) are packaged
      into the virus. tRNA(Lys) packaging (both tRNA(Lys3) and tRNA(Lys1,2) is
      dependent upon the presence of RT sequences within Pr160gag-pol. In this work, we
      have monitored the effect of Pr160gag-pol mutations upon incorporation of
      tRNA(Lys3) and Pr160gag-pol into HIV-1 produced from COS-7 cells transfected with
      mutant HIV-1 proviral DNAs. Mutations include carboxy deletions of Pr160gag-pol
      and small amino acid insertions and replacements within the various functional
      domains of the reverse transcriptase (RT). tRNA(Lys3) incorporation was monitored
      both by 2D PAGE of viral RNA, and by hybridization with tRNA(Lys3)-specific DNA
      probes. Our data indicates: (1) deletion of integrase sequence has a moderate
      effect upon select tRNA(Lys3) packaging, while carboxy terminal deletions
      extending further into the RNase H and connection domains more strongly reduce
      viral tRNA(Lys3) content; (2) tRNA(Lys3) incorporation is strongly reduced by
      small inframe amino acid insertions or replacements in the carboxy region of the
      thumb domain and the amino half of the connection domain of RT, but tRNA(Lys3)
      incorporation is altered little, or not at all, by similar amino acid insertional
      mutations within other RT domains, such as the fingers, palm, RNase H, the amino
      portion of the thumb, and the carboxy region of the connection domain. The
      inability of connection domain mutant virus to incorporate tRNA(Lys3) and to
      properly process precursor proteins in the virus is due to the inability of
      mutant Pr160gag-pol to be incorporated into the virus. These mutant precursor
      proteins are maintained at levels in the cytoplasm similar to wild-type.

PMID- 9034362
TI  - The structure of the complex between rubisco and its natural substrate ribulose
      1,5-bisphosphate.
AB  - The three-dimensional structure of the complex of ribulose 1,5-bisphosphate
      carboxylase/oxygenase (rubisco; EC 4.1.1.39) from spinach with its natural
      substrate ribulose 1,5-bisphosphate (RuBP) has been determined both under
      activating and non-activating conditions by X-ray crystallography to a resolution
      of 2.1 A and 2.4 A, respectively. Under activating conditions, the use of calcium
      instead of magnesium as the activator metal ion enabled us to trap the substrate
      in a stable complex for crystallographic analysis. Comparison of the structure of
      the activated and the non-activated RuBP complexes shows a tighter binding for
      the substrate in the non-activated form of the enzyme, in line with previous
      solution studies. In the non-activated complex, the substrate triggers isolation
      of the active site by inducing movements of flexible loop regions of the
      catalytic subunits. In contrast, in the activated complex the active site remains
      partly open, probably awaiting the binding of the gaseous substrate. By
      inspection of the structures and by comparison with other complexes of the enzyme
      we were able to identify a network of hydrogen bonds that stabilise a closed
      active site structure during crucial steps in the reaction. The present structure
      underlines the central role of the carbamylated lysine 201 in both activation and
      catalysis, and completes available structural information for our proposal on the
      mechanism of the enzyme.

PMID- 9034363
TI  - Predicting conserved water-mediated and polar ligand interactions in proteins
      using a K-nearest-neighbors genetic algorithm.
AB  - Water-mediated ligand interactions are essential to biological processes, from
      product displacement in thymidylate synthase to DNA recognition by Trp repressor,
      yet the structural chemistry influencing whether bound water is displaced or
      participates in ligand binding is not well characterized. Consolv, employing a
      hybrid k-nearest-neighbors classifier/genetic algorithm, predicts bound water
      molecules conserved between free and ligand-bound protein structures by examining
      the environment of each water molecule in the free structure. Four environmental
      features are used: the water molecule's crystallographic temperature factor, the
      number of hydrogen bonds between the water molecule and protein, and the density
      and hydrophilicity of neighboring protein atoms. After training on 13 non
      homologous proteins, Consolv predicted the conservation of active-site water
      molecules upon ligand binding with 75% accuracy (Matthews coefficient Cm = 0.41)
      for seven new proteins. Mispredictions typically involved water molecules
      predicted to be conserved that were displaced by a polar ligand atom, indicating
      that Consolv correctly assesses polar binding sites; 90% accuracy (Cm = 0.78) was
      achieved for predicting conserved active-site water or polar ligand atom binding.
      Consolv thus provides an accurate means for optimizing ligand design by
      identifying sites favored to be occupied by either a mediating water molecule or
      a polar ligand atom, as well as water molecules likely to be displaced by the
      ligand. Accuracy for predicting first-shell water conservation between
      independently determined structures was 61% (Cm=0.23). The ability to predict
      water-mediated and polar interactions from the free protein structure indicates
      the surprising extent to which the conservation or displacement of active-site
      bound water is independent of the ligand, and shows that the protein micro
      environment of each water molecule is the dominant influence.

PMID- 9034364
TI  - The pathobiology of the oligodendrocyte.

PMID- 9034365
TI  - Immunocytochemical co-localization of the proteasome in ubiquitinated structures
      in neurodegenerative diseases and the elderly.
AB  - To determine at the tissue level whether the proteasome (Ps), a unique
      nonlysosomal protease, is involved in the metabolism of ubiquitinated proteins,
      we examined for the first time the immunocytochemical localizations of both Ps
      and ubiquitin (Ub) in sections of various abnormal structures that are known to
      be ubiquitinated in various neurodegenerative diseases and in the elderly.
      Concomitant increases of Ps and Ub were observed at the sites of most dystrophic
      neurites in Alzheimer disease (AD) and parkinsonism-dementia complex on Guam
      (PDC) and in Lewy bodies in Parkinson's disease and diffuse Lewy body disease,
      but not in neurofibrillary tangles in AD or PDC, in filamentous inclusions within
      anterior horn cells in sporadic motor neuron disease, or in eosinophilic granules
      in the olivary nucleus of the elderly. These results at the tissue level
      indicated that Ps is involved in the metabolism of some, but not all,
      ubiquitinated proteins and structures in various neurodegenerative disorders.
      This suggests that the involvement of Ps in the metabolism of ubiquitinated
      structures differs in different cases and at different stages of disease. These
      results and our previous immunocytochemical studies of lysosomal cathepsin
      proteases suggest that both nonlysosomal and lysosomal systems are involved in
      the metabolism of various ubiquitinated proteins and that their involvements
      differ in different structures and at different stages of degeneration of the
      structures.

PMID- 9034366
TI  - The subthalamic nucleus in Parkinson's disease and progressive supranuclear
      palsy.
AB  - The subthalamus has become a promising target for the neurosurgical treatment of
      parkinsonian symptoms. We have used unbiased counting techniques to quantify the
      neuronal populations of the subthalamic nucleus in patients with idiopathic
      Parkinson's disease and progressive supranuclear palsy. In addition, the type of
      calcium binding proteins contained within these subthalamic neurons was
      established using immunohistochemistry. Most of the 550,000 subthalamic neurons
      contain either parvalbumin or calretinin calcium binding proteins, and patients
      with idiopathic Parkinson's disease sustained no damage to this nucleus. This is
      consistent with current theories of basal ganglia circuitry, which postulate that
      overstimulation of this excitatory nucleus contributes to the inhibition of the
      motor thalamus via the activation of inhibitory relays. In contrast, we found
      that there was substantial cell loss in the subthalamus in progressive
      supranuclear palsy (45 to 85% neuronal reduction) and that both cell types were
      equally affected. Extracellular neurofibrillary tangles as well as tau-positive
      glia were observed in the subthalamus of these cases. As the patients with
      Parkinson's disease and progressive supranuclear palsy all had overlapping
      parkinsonian symptoms, the loss of subthalamic stimulation within the basal
      ganglia of progressive supranuclear palsy cases is puzzling, unless their
      parkinsonian symptoms were generated by an alternate mechanism.

PMID- 9034367
TI  - Microglial cell activation in aging and Alzheimer disease: partial linkage with
      neurofibrillary tangle burden in the hippocampus.
AB  - Microglial cells are the main component of the brain's resident immune system and
      are activated in Alzheimer disease (AD). We quantified the density of activated
      microglial cells (AMG) in 8 sectors of human hippocampus to determine if their
      density is correlated with senile plaque (SP) and neurofibrillary tangle (NFT)
      formation. Ferritin-stained microglia, Bielschowsky-stained neuritic plaques, and
      perikarya containing NFTs were counted in 8 young adults, 9 nondemented elderly
      adults, and 9 demented patients with AD. Microglial cell activation was
      moderately higher in elderly nondemented subjects. In AD there was a more
      striking activation in all sectors of the hippocampus. Most AMGs were distributed
      diffusely in neuropil and were not delimited to SPs or NFTs. Senile plaque counts
      were not linked with AMG counts within any sector. Neurofibrillary tangle counts
      were correlated significantly with AMG counts within one sector, the subiculum.
      When variations within and between sectors were factored out statistically, the
      burden of AMGs was correlated significantly with the burden of NFTs (r = 0.34; p
      < 0.005), but not SPs. Neuropathologic changes at the origin of the perforant
      pathway were correlated significantly with orthograde microglial cell activation
      in the termination field. These observations show that correlations between
      microglial cell activation and pathologic features of AD are only rarely
      significant. When significant linkage was present, it involved NFTs and not SPs,
      and depended on which sector of hippocampus was examined.

PMID- 9034369
TI  - Prevalence and disease associations of argyrophilic grains of Braak.
AB  - Braak's argyrophilic grains (BAG) are spindle-shaped structures originally
      described in patients with dementia. We have determined that the prevalence of
      BAGs in an unselected series of 300 consecutive autopsies of subjects over the
      age of 30 is 5.6%, or 11.7% if only subjects older than 65 are considered. All
      the 17 subjects identified were older than 68; 6 received other neuropathological
      diagnoses of degenerative disease and 11 did not. Only 2 of the latter had shown
      clinical evidence of mental impairment. Braak's argyrophilic grains were
      associated with ballooned neurons, superficial linear spongiosis, and gliosis of
      entorhinal cortex and amygdala. Subcortical neurofibrillary tangles were
      consistently found in patients with dementia, but not in other subjects. In a
      separate series studying the prevalence of BAG in neurodegenerative diseases, we
      found a strong, but not universal association with progressive supranuclear
      palsy, and to a lesser degree with the lobar atrophies (Pick's disease and
      corticobasal ganglionic degeneration). Numerous BAG were present in occasional
      cases of diffuse Lewy body disease, multiple systems atrophy, and motor neuron
      disease. We conclude that rather than defining a single disease, BAG constitute
      lesions that accompany several degenerative diseases, but also occur in normal
      elderly subjects, and rarely in demented subjects without other major
      histological findings.

PMID- 9034368
TI  - Apoptosis-related proteins in skeletal muscle fibers of spinal muscular atrophy.
AB  - There is evidence that apoptosis in spinal muscular atrophies (SMA) is not
      restricted to motor neurons but also affects muscle fibers. Studying the
      expression of several apoptosis-associated proteins we found constant expression
      of bax in muscle fibers, which promoted cell death. The expression of bax
      correlated with defective innervation of muscle fibers was also indicated by
      upregulation of N-CAM. While in early-onset SMA atrophic as well as normo- and
      hypertrophic muscle fibers displayed expression of bax, muscle fibers in late
      onset SMA and peripheral neuropathies showed bax-expression only in atrophic
      fibers. Other investigated apoptosis-associated factors comprised interleukin-1
      beta converting enzyme (ICE), mediating cell death by cleavage of actin
      filaments, as well as bcl-2 and bcl-x, both inhibiting apoptosis by acting as
      antioxidants. They were only expressed in atrophic muscle fibers, predominantly
      in late-onset SMA and peripheral neuropathies. We consider the lack of expression
      of these apoptosis-related proteins in early infantile SMA to be associated with
      muscle fiber immaturity due to defective innervation and suggest that immature
      muscle fibers are not able to produce sufficient levels of some proteins. A
      sufficient amount of expression of apoptosis-protecting factors such as bcl-2 is
      needed to neutralize high bax-levels, and a lack of this expression will
      secondarily promote muscle fiber death in defective innervation.

PMID- 9034370
TI  - The effects of additional pathology on the cognitive deficit in Alzheimer
      disease.
AB  - The diagnosis of Alzheimer disease (AD) according to current criteria is a
      combined clinical and pathological exercise. The clinical discrimination of AD
      from other types of dementia may be complicated when the patient suffers from
      more than one disease. In particular the concomitant presence of other
      neurological conditions may significantly influence the severity of cognitive
      deficit. In this study we analyze the extent of the influence of vascular and
      other neurodegenerative pathology on the cognitive deficit in a consecutive
      series of 88 prospectively assessed elderly subjects. We find that, for any given
      level of cognitive deficit, the densities of either all plaques or neuritic
      plaques alone in the neocortex are significantly lower in cases of AD mixed with
      other CNS pathology than in cases of AD with no other CNS pathology. In AD
      combined with cerebrovascular disease, the total plaque density makes a
      significant contribution to cognitive deficit, while neurofibrillary tangle (NFT)
      densities do not. In contrast, in pure AD tangle density is the major determinant
      of cognitive deficit. Our findings draw attention to the influence of coexisting
      brain pathologies on the clinical manifestation of dementia in subjects with AD.
      These findings indicate that pathological diagnostic criteria for AD should take
      into account such additional pathology in demented subjects. They also improve
      understanding of the circumstances in which the amyloid component of AD can play
      a decisive role in precipitating clinical dementia.

PMID- 9034371
TI  - Light and electron microscopic analysis of the central and peripheral nervous
      systems of acid sphingomyelinase-deficient mice resulting from gene targeting.
AB  - The acid sphingomyelinase (aSmase)-deficient mouse line recently generated by
      gene targeting (Otterbach and Stoffel, 1995) develops a lethal storage disease
      which is phenotypically comparable to the neurovisceral form of the human
      sphingomyelinosis, Niemann-Pick disease type A (NPA). This report describes the
      progressive accumulation of uncatabolized lipid substrates at the cellular and
      ultrastructural level in different regions of the nervous system of homozygous
      aSmase-/- mice, including cerebrum, cerebellum, spinal cord, optic nerve and
      peripheral nerves. We saw a cytoplasmic accumulation of pleomorphic lysosomal
      structures in cells of all regions under study, most extensively in macrophages,
      vascular endothelial cells, and also in neuronal perikarya. The complete and
      early degeneration of Purkinje cells was particularly striking. Moreover, we
      found a storage material in the cytoplasm of Schwann cells and to a minor extent
      in oligodendrocytes. In most advanced stages of the disorder, we detected an
      axonal dystrophy in both the central nervous system (CNS) and peripheral nervous
      system (PNS), without signs of dysmyelination or demyelination. The morphological
      changes of the central and peripheral nervous systems in the homozygous aSmase-/-
      mouse line closely resemble those in human NPA.

PMID- 9034372
TI  - Amplification and overexpression of MDM2 in primary (de novo) glioblastomas.
AB  - Glioblastoma multiforme (WHO Grade IV), the most malignant neoplasm of the human
      nervous system, develops rapidly de novo (primary glioblastoma) or through
      progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). We
      recently reported that mutations of the p53 gene are present in more than two
      thirds of secondary glioblastomas but rarely occur in primary glioblastomas,
      suggesting the presence of different genetic pathways (Watanabe et al, Brain
      Pathol 1996:6:217-24). In the present study, primary and secondary glioblastomas
      were screened by immunohistochemistry for MDM2 overexpression and by differential
      PCR for gene amplification. Tumor cells immunoreactive to MDM2 were found in 15
      of 29 primary glioblastomas (52%), but in only 3 of 27 secondary glioblastomas
      (11%; P=0.0015). MDM2 amplification occurred in 2 primary (7%) glioblastomas but
      in none of the secondary glioblastomas. Only one out of 15 primary glioblastomas
      overexpressing MDM2 contained a p53 mutation. These results suggest that MDM2
      overexpression with or without gene amplification constitutes a molecular
      mechanism of escape from p53-regulated growth control, operative in the evolution
      of primary glioblastomas that typically lack p53 mutations.

PMID- 9034373
TI  - Distinct neurodevelopmental patterns of bcl-2 and bcl-x expression are altered in
      glioneuronal hamartias of the human temporal lobe.
AB  - Bcl-2 and bcl-xL are homologous proteins that inhibit cell death and are
      expressed in the nervous system. We tested the hypothesis that aberrant
      expression of such "death suppressor" molecules may promote the survival of
      abnormal cells in glioneuronal lesions associated with temporal lobe epilepsy.
      The normal pattern of bcl-2 and bcl-x expression was studied in postmortem human
      fetal and adult temporal lobes. Formalin-fixed, paraffin-embedded tissue sections
      were probed for bcl-2 and bcl-x in immunohistochemical studies using well
      characterized primary antibodies that had been raised against epitopes that are
      not shared by these proteins. Strong staining for both proteins was observed in
      the ventricular zone and in migrating, postmitotic and postmigratory young
      neurons of the neocortex, hippocampus, and entorhinal cortex from 6 to 20 weeks
      gestational age (GA). However, bcl-2 immunoreactivity gradually decreased to weak
      or nondetectable levels between 20 and 39 weeks GA, while strong bcl-x staining
      of neurons persisted throughout fetal development and into adulthood. Twenty
      eight temporal lobe resections from children and adults ranging in age from 1 to
      45 years (mean=19 years) with intractable epilepsy were then screened for
      differences in the pattern of bcl-2 and bcl-x expression compared to normal
      controls. Bcl-2 (but not bcl-x) was strongly immunoreactive in small, immature
      appearing cells that were components of microscopic glioneuronal aggregates
      (hamartias) and that have been shown previously to express an embryonic form of
      the neural cell adhesion molecule. These immature cells were immunonegative for
      standard markers of neuronal and glial lineage and were negative for Ki67,
      suggesting that they are post-mitotic. The persistent expression of bcl-2 and
      apparent downregulation of bcl-x in these cells represent deviations from the
      normal ontogeny of these molecules in the human nervous system. These data
      suggest that dysregulation of bcl-2 and related proteins may be involved in the
      pathogenesis of some temporal lobe malformative lesions.

PMID- 9034374
TI  - Human fascia dentata anatomy and hippocampal neuron densities differ depending on
      the epileptic syndrome and age at first seizure.
AB  - This study determined fascia dentata anatomy and hippocampal neuron densities in
      patients with different epileptic syndromes. Based on presurgical data, patients
      were classified into: (a) pediatric patients (n=19); (b) temporal mass lesion
      cases (n=14); and (c) hippocampal sclerosis patients (n=31). Surgically removed
      hippocampi and autopsies (n=34) were studied for: (a) hippocampal neuron
      densities; (b) stratum granulosum (SG) widths and lengths; and (c) hilar areas.
      The number of granule cells and hilar neurons per tissue section were estimated
      from the neuron densities and fascia dentata area measurements. Results showed
      that compared with autopsies (p<0.05): (a) pediatric patients had similar SG and
      hilar areas; granule cell density was lower (but not hilar neuron density); and
      the estimated number of granule cells was lower (but not the number of hilar
      neurons); (b) the widths of SG and hilar areas were greater in mass lesion cases;
      the density of granule cells and hilar neurons was lower; and the total estimated
      numbers of granule cells and hilar neurons were similar to those of the
      autopsies; and (c) hippocampal sclerosis patients had wider, yet shorter SG;
      hilar areas were smaller; granule cell and hilar densities were lower; and the
      total estimated numbers of granule cells and hilar neurons were lower than those
      of the autopsy cases. The duration of the seizures did not correlate with lower
      fascia dentata neuron densities or estimates of total granule cell and hilar
      neurons. Furthermore, greater SG widths correlated with lower hilar and CA4
      neuron densities, but not with age at first seizure or duration of epilepsy.
      These results indicate that the size of the fascia dentata SG and hilus along
      with hippocampal neuron densities differ between surgical patients with different
      epileptic syndromes, and a wider SG was associated with a lower density of end
      folium neurons. These findings support the hypothesis that hippocampal sclerosis
      and granule cell dispersion are not the consequence of repetitive seizures
      beginning at an early developmental age, but seem to differ depending on the type
      of epileptic syndrome.

PMID- 9034375
TI  - The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis.

PMID- 9034376
TI  - The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis.

PMID- 9034377
TI  - The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis.

PMID- 9034378
TI  - The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis.

PMID- 9034401
TI  - Associations between candidate loci angiotensin-converting enzyme and
      angiotensinogen with coronary heart disease and myocardial infarction: the NHLBI
      Family Heart Study.
AB  - Angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) are major
      components of the renin-angiotensin systems. An association between myocardial
      infarction (MI) and the ACE DD genotype of the insertion/deletion (ID)
      polymorphism in intron 16 of the ACE gene has been reported. However, other
      similarly designed studies have not found such an association. Angiotensin II,
      the product of AGT, has a direct effect on vascular tone; and a variant in the
      AGT gene has been found to be associated with MI in the Japanese. This case
      control study was initiated to investigate whether the ACEI/D and AGT M235T
      polymorphisms are associated with an increased risk for coronary heart disease
      (CHD) and MI. Our study groups were composed of participants in the National
      Heart Lung Blood Institute (NHLBI) Family Heart Study (FHS) selected from three
      population-based studies: two Atherosclerosis Risk in Communities (ARIC) centers
      (Forsyth County, NC, and Minneapolis, MN), and the Framingham Heart Study. In
      multivariate analysis within ARIC Caucasians, a significant positive association
      was found between CHD (controls = 230, cases = 232) and the AGT TT genotype (P =
      0.022; OR = 1.84, 1.09-3.10 95% CI). When we restricted the analysis to a low
      risk group for CHD (controls = 70, cases = 35) an interaction between the ACE DD
      and AGT TT genotypes was significant (P = 0.025; OR = 5.02 1.22-20.6 95% CI).
      After further subsetting low-risk cases to those with a definite MI (controls =
      74, cases = 16), we found that the associations with the ACE DD genotype was also
      significant (P = 0.013, OR = 3.94, 1.28-12.2 95% CI). Comparable tests in the
      Framingham sample failed to support an association of these markers with CHD. In
      conclusion, within selected groups the ACE D and AGT 235T alleles are
      statistically associated with CHD and MI, and there is a synergistic interaction
      between the two alleles. These results and those from previous studies together
      suggest that the association of these two loci is neither strong nor consistent
      and involves a complex interaction among risk factors and genotypes.

PMID- 9034402
TI  - Associations of candidate loci angiotensinogen and angiotensin-converting enzyme
      with severe hypertension: The NHLBI Family Heart Study.
AB  - PURPOSE: In studies conducted in several different populations, the M235T
      substitution in the angiotensinogen (AGT) locus has been associated with
      hypertension. METHODS: A case-control study was initiated in an attempt to
      replicate this finding. Persons with hypertension, age- and sex-matched
      normotensive controls, and randomly sampled individuals were probands from the
      Family Heart Study of the National Heart, Lung, and Blood Institute. Subjects
      were recruited from the Atherosclerosis Risk in Communities study (ARIC) in North
      Carolina and Minneapolis, MN, and from the Framingham Heart Study in
      Massachusetts. Genotypes were determined for the M235T substitution in the AGT
      locus and for the insertion/deletion polymorphism in the angiotensin-converting
      enzyme (ACE) locus. Simple association tests as well as logistic regression
      analyses were performed. RESULTS: The association of AGT-T235 with hypertension
      was replicated in the Framingham sample (odds ratio, 1.60; 95% confidence
      interval, 1.11-2.30), but not in the ARIC white or black subjects. However,
      logistic regression analysis suggested a significant association of AGT with
      hypertension in both the ARIC white and Framingham samples when the effects of
      body mass index, triglycerides, and the presence of significant coronary heart
      disease were controlled. These analyses further suggested that, in the ARIC data,
      the relationship with the AGT locus is stronger in women than men and that there
      may be interaction (epistasis) between homozygotes for T235 and ACE-DD in the
      Framingham data. While the small sample size precluded logistic regression
      analysis, the frequency of the T235 allele in the black random sample was much
      higher than in the comparable white sample. CONCLUSIONS: These results are
      compatible with the presence of a genetic risk factor for hypertension in or near
      the angiotensinogen locus.

PMID- 9034403
TI  - Lifestyle, education, and prevalence of hypertension in populations of African
      origin. Results from the International Collaborative Study on Hypertension in
      Blacks.
AB  - Lifestyle Incongruity has been shown to be associated with elevated blood
      pressure in various developing societies. We sought to test this model in an
      international collaborative study of hypertension in populations of African
      origin. Data were available for 4770 men and women, aged 25-74, from Africa, the
      Caribbean, and the United States. The main effects of lifestyle score (LSS) and
      education on hypertension prevalence were explored, as well as interactions
      predicted by the Lifestyle Incongruity model. Significant interactions were
      observed, but only the U.S. men conformed to the pattern predicted. For this
      group, adjusted ORs for LSS were 4.45 among low-education and 0.71 among high
      education subgroups (risk OR = 0.16, 0.03-0.84 95% CI). The Lifestyle Incongruity
      model therefore received limited support. The model was designed to describe
      processes in societies experiencing modernization and opportunities for lifestyle
      differentiation, conditions that may not have been met in some sites.

PMID- 9034404
TI  - A probability-based approach for predicting HIV infection in a low prevalent
      population of injection drug users.
AB  - This article proposes a method for estimating HIV risk in low-HIV-prevalent
      populations. Allard's risk probability model was used to compute individual risk
      scores. Based on a sample of 3854 injection drug users (IDUs) who were
      confidentially tested for HIV at five methadone treatment clinics in Los Angeles
      County, the following self-reported risk behaviors were used to derive an
      individual IDU risk score: (i) frequency of injection, (ii) frequency of using
      uncleaned needles, (iii) number of people sharing a needle, (iv) frequency of
      needle sharing, and (v) type of needle sharing practice. The overall HIV
      prevalence for the IDU sample was 2%. The risk score was strongly associated with
      HIV seropositivity (chi-square = 16.1, p < 0.0001), but only one of the
      individual IDU risk behaviors (needle cleaning) was significantly associated with
      HIV seropositivity (chi-square = 10.9, P < 0.001). In addition, the risk score
      was strongly associated with HIV serostatus for both males and females. For
      females, however, none of the individual IDU risk behaviors were associated with
      HIV serostatus. Our findings indicate that when predicting HIV infection in a low
      prevalence population, the probability-based risk score makes a statistically
      significant contribution over individual IDU risk behaviors.

PMID- 9034405
TI  - Geographic trends in prostate cancer mortality: an application of spatial
      smoothers and the need for adjustment.
AB  - Prostate cancer mortality among whites and nonwhites in U.S. counties are
      analyzed for geographic effects. To better visualize geographical effects, the
      data are smoothed with a bivariate smoother using age-specific rates. Among
      nonwhites, an important explanatory variable is the proportion of African
      Americans. A relationship between the mortality rate and this variable is
      derived, and the data are adjusted for this variable using this relationship.
      When the rates are adjusted for age only, among whites there is a north-south
      gradient: rates are higher in the north, lower in the south. Among nonwhites, the
      gradient runs east to west: higher in the east, lower in the west. The latter
      gradient disappears when the rates are further adjusted for African Americans.
      The study reveals the importance of both smoothing the data to visualize patterns
      in geography and adjusting the data for an important variable to identify
      underlying patterns. The additional adjustment permits the identification of
      other areas of the country with elevated or depressed rates.

PMID- 9034406
TI  - Exercise, occupational activity, and risk of endometrial cancer.
AB  - We conducted a case-control study in western New York state among 232 women with
      newly-diagnosed endometrial cancer and 631 controls selected from the community.
      Physical activity was measured by participation in vigorous exercise and walking
      at four time periods: at age 16, and at 20, 10, and 2 years before the interview
      and by occupational activity based on a detailed lifetime history. Women who did
      a moderate amount of vigorous exercise at age 16 and at 20 years before the
      interview were at reduced risk as compared with those who reported no activity,
      with odds ratios (OR) (95% confidence intervals) of 0.51 (0.31-0.83) and 0.50
      (0.29-0.89), respectively. However, there was no evidence of declining risk with
      greater amount of activity. At later times, 10 years and 2 years before the
      interview, being in the highest group with regard to vigorous activity was
      associated with a slightly but nor significant lower risk as compared with women
      who reported no activity; the adjusted OR were 0.72 (0.43-1.19) and 0.67 (0.42
      1.09), respectively. Being in the highest category of miles walked at age 16
      (i.e., > or = 15 miles per week) was associated with a slightly reduced risk as
      compared with not walking at all (OR 0.64 (0.26-1.16)), whereas the number of
      miles walked at other times was not related to reduced risk. Occupational
      physical activity was not related to the risk of endometrial cancer. Overall,
      these results indicate that physical activity at levels prevalent in this
      population has at most a modest relationship to reduced risk of endometrial
      cancer.

PMID- 9034407
TI  - Physical activity, functional limitations, and the risk of fall-related fractures
      in community-dwelling elderly.
AB  - This case-control study examines the association of vigorous and mild physical
      activity with fall-related fractures in a community-dwelling population age 65
      and older in South Florida. Vigorous physical activity was defined as exercising,
      doing heavy housecleaning, or other hard labor three or more times per week in
      the month prior to the index date; mild physical activity was defined as the
      number of hours per day subjects reported spending on their feet. A case was any
      subject who sustained a fall-related fracture (ICD-9CM-800 through ICD-9CM-829)
      over a 21-month period (n = 471). Controls were at 10% random sample selected
      from the Health Care Financing Administration Medicare files (n = 712). The
      presence of any limitation in activities of daily living (ADL) significantly
      modified the effect of vigorous physical activity. Physically active subjects
      with no limitations (ADL = 0) were less likely to sustain a fall-related fracture
      than were inactive subjects with an adjusted odds ratio (aOR) of 0.6, (0.5-0.8
      95% CI), and active subjects with any limitation (ADL > or = 1) had an aOR of 3.2
      (1.1-9.8 95% CI). Limiting this analysis to 159 hip fracture cases produced
      similar results. Mild physical activity was not associated with fracture. These
      results suggest that vigorous physical activity is associated with a lower
      fracture risk among elderly persons who have no limitation in ADL and with a
      higher risk among those with any limitations.

PMID- 9034408
TI  - Iron status and risk of cardiovascular disease.
AB  - Free Iron, as well as other transition metals, can catalyze free radical
      formation. For this reason iron is tightly bound to transport and storage
      proteins to prevent their involvement in free radical formation. It has been
      hypothesized that increased iron intake or iron stores may promote atherogenesis
      by increasing free radical formation and oxidative stress. While a coherent,
      plausible hypothesis as to how transition metals, such as iron, might accelerate
      the progression of atherosclerosis has been generated from basic research, iron
      status, measured as dietary iron intake, serum iron, serum ferritin, and
      transferrin saturation, has been inconsistently associated with cardiovascular
      disease in human epidemiologic research. In addition, limited data suggest that
      iron overload states do not appear to be strongly associated with increased risk
      of atherosclerotic disease. One real limitation of the existing data is the lack
      of a generally agreed upon and logistically feasible means of assessing iron
      status in free living humans. Further research, including basic research and
      large-scale epidemiologic studies, is needed to fully assess the association
      between iron status and the risk of CVD and other adverse outcomes. At present
      the currently available data do not support radical changes in dietary
      recommendations or screening to detect high normal levels nor do they support the
      need for large-scale randomized trials of dietary restriction or phlebotomy as a
      means of lowering iron stores.

PMID- 9034409
TI  - Physical activity protects against coronary death and deaths from all causes in
      middle-aged men. Evidence from a 20-year follow-up of the primary prevention
      study in Goteborg.
AB  - We set out to examine the long-term effect of work-related and leisure time
      physical activity on risk of death from coronary heart disease (CHD) and other
      causes. Data were obtained from a large prospective population study of 7142
      participant men aged 47 to 55 years at baseline in 1970-1973 and without
      symptomatic CHD. Data on physical activity at work and at leisure were assessed
      by way of a questionnaire. After 20 years follow-up men with physically demanding
      work had a slightly higher mortality from all causes, but not from CHD. The
      association with all-cause mortality disappeared after controlling for smoking,
      occupational class, and alcohol abuse. Men who were physically active during
      leisure time had a lower risk of death from CHD, cancer, and all causes. After
      controlling for smoking, diastolic blood pressure, serum cholesterol, body mass
      index, diabetes alcohol abuse, and low occupational class, the most active men
      had a relative risk (RR) of dying from CHD of 0.72 (0.56-0.92 95% CI) and of all
      causes of 0.70 (0.61-0.80 95% CI). The adjusted relative risk for cancer death
      was of borderline significance. Noncardiovascular deaths other than cancer showed
      a strong relationship with low physical activity in the present study that
      remained after controlling for smoking, alcohol abuse, and other factors
      (adjusted RR 0.55 (0.42-0.73 95% CI)). The protective effect of CHD and on
      mortality was present after excluding the first 8 years of follow-up, and at all
      levels of other risk factors, such as smoking, diastolic blood pressure, serum
      cholesterol, and body mass index. In conclusion, this long-term study
      demonstrates the protective effect of leisure time physical activity on CHD
      death, cancer death, and on death from all causes. The effect on coronary death
      and on death from all causes was independent of other risk factors.

PMID- 9034410
TI  - The differences in diabetes risk in blacks and whites.

PMID- 9034411
TI  - Economic impact with home delivery of chemotherapy to pediatric oncology
      patients.
AB  - OBJECTIVE: To examine the economic impact of a home chemotherapy program (HCP)
      for pediatric oncology patients. RATIONALE: Factors that led to initiation of an
      HCP included availability of specially trained nurses and programmable ambulatory
      infusion devices at local home care agencies, routine central venous catheter
      placement, inpatient bed space shortages, and the availability of ondansetron.
      SETTING: Chemotherapy delivery in the home setting from June 1991 through June
      1994. DESIGN: Charge data and nausea and vomiting severity data were collected
      for patients treated through the HCP. METHODS: Economic impact was calculated by
      incorporating and summing all charge categories associated with hospital
      admission for chemotherapy (HAC) versus delivery by the HCP. All data were
      adjusted for 1993 dollars, and reflect changes for the average patient size (1
      m2). Charge data for each chemotherapy protocol delivered in the home were
      analyzed by calculating the differences between HAC and HCP charges using the
      following formula: charge difference (HAC - HCP) per protocol times the number of
      courses. Total economic impact was calculated by summing the differences in
      charges for each protocol. RESULTS: A total of 262 chemotherapy courses were
      given to 44 patients (mean age 9.5 +/- 5.1 y) through the HCP, which represented
      1012 patient care days and 24 different chemotherapy protocols. Monetary savings
      from the HCP ranged from $5180 per course of ifosfamide plus etoposide to $367
      per course for high-dose methotrexate. Total monetary savings from the HCP during
      the 3-year period was $640,793. Successful control of nausea and vomiting with a
      combination of ondansetron plus methylprednisolone was achieved in approximately
      80% of the patients receiving highly emetogenic chemotherapy protocols.
      CONCLUSIONS: HCP for pediatric oncology patients results in substantial monetary
      savings to payors. Effective control of nausea and vomiting can be accomplished
      at home in the majority of patients with an ondansetron-based antiemetic regimen.

PMID- 9034412
TI  - Sedatives, analgesics, and paralytics in the ICU.
AB  - OBJECTIVE: To solicit practitioner-perceived opinions regarding current
      sedative/analgesic/paralytic practice including drug selection, admixture
      methods, and methods of assessing patient response to therapy via surgery tool;
      and to assess sedative/pain/paralytic drug use patterns including dosage, route
      selection, and combination therapy by collecting actual drug administration data
      from multiple centers. METHODS: Respondents completed a survey and collected drug
      administration data for 5 consecutive days in the intensive care unit (ICU) in
      which they practiced. PARTICIPANTS: One hundred thirty-eight members of the
      Society of Critical Care Medicine Clinical Pharmacology and Pharmacy section and
      the Critical Care Practice Research Network of the American College of Clinical
      Pharmacy agreed to participate in the study. RESULTS: Fifty-one percent of the
      participants completed surveys, and 45% returned drug administration data
      collection forms. Patients received sedative/pain/paralytic therapy 62% of the 5
      days studied. The most frequently received drugs were opiates, followed by
      benzodiazepines. Intermittent intravenous injection, oral/enteral, and continuous
      infusion methods were used in most patients. Combination therapy was used 25% of
      the time, with benzodiazepine/opiate combinations used most often (46%).
      Administration protocols were rarely used. Paralytic agents were occasionally
      administered without sedative/pain therapy. CONCLUSIONS: Patients received these
      agents during the majority of their ICU stay. Multicenter drug use data suggested
      a preference for opiate and benzodiazepine therapy. Many centers used continuous
      infusion therapy despite minimal pharmacokinetic/pharmacodynamic information on
      ICU patients. Further studies are needed to standardize end points, as well as
      obtain both pharmacokinetic/pharmacodynamic and stability data in ICU patients.

PMID- 9034413
TI  - Factors associated with antihypertensive prescribing.
AB  - OBJECTIVE: To investigate factors associated with treatment approaches to
      hypertension, a major risk factor for coronary heart and cerebrovascular disease
      and significant healthcare problem in the US. The study reports on three cross
      sectional national surveys of patient-physician encounters. POPULATION: Visits
      were selected for adults with hypertension diagnoses from the National Ambulatory
      Medical Care Surveys, which represent office encounters during a given year.
      Years of observation included 1989, 1990, and 1991. METHODS: Multiple variable
      logistic regression was used to identify predisposing need, enabling, and health
      utilization characteristics associated with whether the visit resulted in a
      prescription of an antihypertensive. Additionally, the association of these
      visits with combination therapy is determined. RESULTS: For each of the 3 years,
      69-75% of the encounters were associated with a prescription for drugs to treat
      hypertension. Prescribing is consistent with current literature demonstrating
      decreasing reliance on diuretics and beta-blockers, and increasing reliance on
      calcium antagonists. Combination therapy decreased as a percentage of
      prescriptions in 1990 and 1991. Variables associated with receiving an
      antihypertensive prescription included predisposing characteristics (patient age
      > 65 y), need characteristics (diagnosis of congestive hear failure [CHF]), and
      health utilization characteristics (physician specialty, previous diagnosis of
      hypertension). The most significant variables associated with combination therapy
      were predisposing characteristics (patient age > 65 y), need (CHF diagnosis,
      diagnosis of hypertension with end organ involvement), and health utilization
      characteristics (physician specialty). CONCLUSIONS: These national estimates
      reinforce previous regional data regarding the categories of hypertension
      medications used. Patient visits involving multiple diagnoses, cardiologists, or
      patients older than 65 years, are more likely to generate prescriptions for
      combination antihypertensive therapy.

PMID- 9034414
TI  - Prevalence of inhaled corticosteroid use among patients with chronic obstructive
      pulmonary disease: a survey.
AB  - OBJECTIVE: To determine the extent of inhaled corticosteroid use among patients
      with chronic obstructive pulmonary disease (COPD). DESIGN: Review of medical
      records. SETTING: Tertiary-care university teaching hospital. PATIENTS: Seventy
      two consecutive patients prescribed an inhaled corticosteroid during
      hospitalization. INTERVENTION: None. MEASUREMENTS: Patient demographics, inhaled
      corticosteroid regimen, respiratory diagnosis, and inhaled corticosteroid use
      before and during hospitalization. RESULTS: The majority of patients (85%) were
      receiving their prescribed corticosteroid inhaler prior to admission.
      Beclomethasone dipropionate 250 micrograms/puff was the most commonly prescribed
      inhaled corticosteroid formulation accounting for 43% of the total corticosteroid
      inhaler orders. COPD was the most common respiratory diagnosis (43%) associated
      with inhaled corticosteroid use, followed by asthma (37%), COPD/asthma (13%), and
      no diagnosis (7%). During the study period, the proportion of all hospitalized
      patients with COPD who also received inhaled corticosteroid prescriptions (35%)
      was not significantly different from all hospitalized patients with asthma who
      received inhaled corticosteroid prescriptions (33%). CONCLUSIONS: The rate of
      inhaled corticosteroid use far exceeds the rate expected among the general
      population of patients with COPD. Educational intervention is needed to encourage
      compliance with published guidelines for the management of COPD.

PMID- 9034415
TI  - Algorithms used in adverse drug event reports: a comparative study.
AB  - OBJECTIVE: To determine if and how the Kramer and Karch algorithms differ in
      assigning a probability that a published case was actually an adverse drug event
      (ADE), and to determine if these algorithms could be used to assess published
      ADEs. DESIGN: Open, single-rater comparison of Karch and Kramer algorithms in 200
      published ADE reports. MAIN RESULTS: The algorithms were not significantly
      different regarding the proportion of cases deemed definite (p = 0.5204) or
      probable (p = 0.2972) ADEs. The Kramer instrument was more likely to assign a
      possible risk of ADE (p = 0.0001), while the Karch instrument was more likely to
      assign a risk of unlikely (p = 0.0001). The algorithms agreed in 41% of the cases
      and could be used to assess published ADEs. CONCLUSIONS: The Karch and Kramer
      algorithms may disagree in how they assign a probability of risk to a potential
      ADE. This may be due to how algorithms are applied, as well as to structural
      differences.

PMID- 9034416
TI  - Lactic acidosis and fatal myocardial failure due to clozapine.
AB  - OBJECTIVE: To describe a patient with neutropenic fever complicated by
      hyperglycemia, lactic acidosis, and fatal myocardial failure associated with
      clozapine therapy. CASE SUMMARY: A 37-year-old Ashkenazic Jewish man was admitted
      for agranulocytosis and fever, which developed after 11 weeks of clozapine
      monotherapy for drug-resistant schizophrenia. Complete blood counts and a routine
      serum chemical analysis had been normal before the treatment was initiated, and
      remained within normal limits during the first 10 weeks of the treatment. On the
      day of admission, the patient deteriorated rapidly and developed extreme
      hyperglycemia, severe lactic acidosis, recurrent cardiac arrest, cardiogenic
      shock, and coma. He died 36 hours later despite intensive treatment. DISCUSSIONS:
      Clozapine intake reduced fatal aganulocytosis, associated with hyperglycemia,
      lactic acidosis, and heart failure. White blood cell count monitoring was
      insufficient to predict these adverse effects. CONCLUSIONS: Clozapine should be
      avoided in high-risk patients (e.g., the elderly, women, Ashkenazic Jews).

PMID- 9034417
TI  - Myoclonus due to chlorambucil in two adults with lymphoma.
AB  - OBJECTIVE: To report myoclonus due to chlorambucil therapy in two adults with
      lymphoma, and to review the literature of chlorambucil neurotoxicity in adults.
      CASE SUMMARIES: Case 1: An 81-year-old man with lymphoma being treated with
      chlorambucil developed jerking movements and stiffness that persisted for 3 days
      and intensified at night. The dosage of chlorambucil was decreased with a
      subsequent decrease in symptomatology. Resolution of the myoclonus occurred with
      discontinuation of the chlorambucil. Rechallenge evoked a return of tremors the
      next day that later became constant and again resolved on discontinuation of
      chlorambucil. Case 2: A 75-year-old woman with lymphoma being treated with
      chlorambucil developed jerking movements in her limbs, particularly in her arms
      and right hip. The symptoms were so severe they prevented the patient from
      leaving her house. All symptoms resolved within 2-3 days after the cycle was
      completed and did not return. She was diagnosed as having had chlorambucil
      induced myoclonus. DATA SOURCES: Searches were performed on MEDLINE, CancerLit,
      and Science Citation Index Review to identify reports and articles discussing
      chlorambucil-induced neurotoxicity, particularly myoclonus. DISCUSSION:
      Chlorambucil-induced myoclonus has been described in overdose situations and in
      the treatment of nephrotic syndrome in children. Three cases of reversible
      myoclonic activity associated with high-dose chlorambucil in adults have also
      been described. In each case, the myoclonus resolved following discontinuation of
      the drug. Only one other conclusive case of low-dose chlorambucil-induced
      myoclonus in an adult has been described. The two cases presented here are unique
      in that the myoclonus occurred in adults receiving low-dose chlorambucil who had
      no myoclonus before or after treatment with the drug. CONCLUSIONS: From the cases
      reviewed, it appears that chlorambucil may induce myoclonus in adults receiving
      therapeutic dosages of chlorambucil. The neurologic status of patients receiving
      chlorambucil should be followed closely during treatment. If myoclonus develops,
      drug-induced myoclonus should be considered, as well as discontinuation of the
      drug.

PMID- 9034418
TI  - Possible serotonin syndrome associated with tramadol and sertraline
      coadministration.
AB  - OBJECTIVE: To report a possible case of serotonin syndrome associated with
      coadministration of tramadol hydrochloride and sertraline hydrochloride. CASE
      SUMMARY: A 42-year-old woman developed atypical chest pain, sinus tachycardia,
      confusion, psychosis, sundowning, agitation, diaphoresis, and tremor. She was
      taking multiple medications, including tramadol and sertraline. The tramadol
      dosage had recently been increased, resulting in what was believed to be
      serotonergic syndrome. DISCUSSION: Serotonin syndrome is a toxic
      hyperserotonergic state that develops soon after initiation or dosage increments
      of the offending agent. Patients may differ in their susceptibility to the
      development of serotonin syndrome. The (+) enantiomer of tramadol inhibits
      serotonin uptake. Tramadol is metabolized to an active metabolite, M1, by the
      CYP2D6 enzyme. If this metabolite has less serotonergic activity than tramadol,
      inhibition of CYP2D6 by sertraline could have been a factor in the interaction.
      CONCLUSIONS: Clinicians should be aware of the potential for serotonin syndrome
      with concomitant administration of sertraline and tramadol.

PMID- 9034419
TI  - Seizure resulting from a venlafaxine overdose.
AB  - OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old
      woman with major depression took an overdose of venlafaxine in an apparent
      suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient
      experienced a witnessed generalized seizure. She was admitted to the medical
      intensive care unit, venlafaxine was discontinued, and no further sequelae were
      seen. DISCUSSION: To our knowledge, this is the first reported case of
      venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose
      pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of
      available interventions, no emergent therapy was instituted. CONCLUSIONS: The
      venlafaxine overdose in our patient resulted in a single episode of generalized
      seizure but elicited no further sequelae.

PMID- 9034420
TI  - Hypoprothrombinemia associated with cefmetazole.
AB  - OBJECTIVE: To report a case of hypoprothrombinemia associated with the use of
      cefmetazole sodium, define patients at risk for this adverse effect, and identify
      options to prevent this problem. CASE SUMMARY: A malnourished patient with
      endstage renal disease received cefmetazole following a below-the-knee amputation
      of the right leg. Three days later, a prothrombin time (PT) and an international
      normalized ratio (INR) were obtained and were markedly elevated from baseline;
      however, the patient had no clinical symptoms of bleeding. Cefmetazole was
      discontinued. Vitamin K and fresh frozen plasma were administered. The PT and INR
      normalized within 24 hours and remained normal throughout the remainder of
      hospitalization. DISCUSSION: The incidence of hypoprothrombinemia associated with
      cefmetazole reported in the literature is conflicting and not consistent. There
      are three proposed mechanisms of cephalosporin-associated hypoprothrombinemia,
      two of which involve the N-methylthiotetrazole (NMTT) chain. The most plausible
      mechanism is NMTT inhibition of vitamin K epoxide reductase in the liver.
      Patients at an increased risk for this adverse event include those with low
      vitamin K stores, specifically patients who are malnourished, with low albumin
      concentrations and poor food intake. The elderly and patients with liver or renal
      dysfunction are examples of populations at risk. CONCLUSIONS: Hypoprothrombinemia
      may occur with cephalosporins and is especially problematic with those containing
      an NMTT side chain. Clinicians need to identify patients at risk for developing
      antibiotic-associated hypoprothrombinemia, monitor them closely, and give vitamin
      K as prophylaxis accordingly.

PMID- 9034421
TI  - Valacyclovir.
AB  - OBJECTIVE: To discuss the clinical pharmacology, antiviral activity, clinical
      efficacy, and other therapeutic issues associated with valacyclovir use for the
      treatment of herpesvirus infections. DATA SOURCE: Literature searches using
      MEDLINE were prospectively designed to include relevant articles and abstracts
      between January 1982 and March 1996. The searches focused on valacyclovir
      pharmacology, clinical efficacy, and issues associated with herpesvirus
      infections. STUDY SELECTION: Selection of clinical and basic science studies were
      limited to those focusing on valacyclovir. All articles with pertinent
      information relevant to the scope of this article were reviewed. DATA SYNTHESIS:
      Valacyclovir is an amino acid ester prodrug of acyclovir. It is currently
      approved for the treatment of herpes zoster infections in immunocompetent adults
      (1 g p.o. tid for 7 d) and recurrent episodes of genital herpes in
      immunocompetent adults (500 mg bid for 5 d). Valacyclovir is rapidly and almost
      completely hydrolyzed to acyclovir prior to systemic exposure. The
      bioavailability of valacyclovir is 54% compared to approximately 20% for oral
      acyclovir. At higher dosages (2 g qid), the plasma AUC of acyclovir following
      oral valacyclovir administration approximates that seen after intravenous
      administration of 10 mg/kg every 8 hours. Clinical data indicate that
      valacyclovir is at least as effective as acyclovir in decreasing the duration of
      pain associated with postherpetic neuralgia, and in reducing time to genital
      lesion healing and the length of the episode. CONCLUSIONS: Valacyclovir has
      improved bioavailability over acyclovir and is at least as efficacious. The
      favorable safety profile of acyclovir and increased systemic exposure make it a
      particularly ideal candidate for further studies of herpes group viral infections
      in immunocompromised patients.

PMID- 9034422
TI  - Dalteparin: a low-molecular-weight heparin.
AB  - OBJECTIVE: To discuss the chemistry, pharmacology, and pharmacokinetics of
      dalteparin, a low-molecular-weight heparin (LMWH), and to review the comparative
      clinical trial data evaluating the efficacy and safety of dalteparin and
      unfractionated heparin (UH) for the prophylaxis and treatment of venous
      thromboembolism. DATA SOURCES: A MEDLINE search identified pertinent English
      language publications on dalteparin and venous thromboembolism. Key search terms
      were dalteparin, Fragmin, LMWH, and venous thromboembolism. The search was
      supplemented by review articles, articles obtained from the bibliographies of the
      review articles, and the dalteparin approval database. STUDY SELECTION: The most
      pertinent studies describing the pharmacology and pharmacokinetics of dalteparin
      in humans were selected; all abstracts and clinical evaluating the use of
      dalteparin for antithrombotic therapy were reviewed. Review articles by authors
      of international reputation were selected. DATA EXTRACTION: Pertinent information
      from the review articles on the pharmacology of LMWHs and UH was summarized.
      Clinical trial data were extracted for study design, patient demographics,
      therapeutic regimens, methods of evaluation, and outcomes. DATA SYNTHESIS:
      Dalteparin is an LMWH indicated for patients undergoing abdominal surgery who are
      considered to be at risk for deep-vein thrombosis (DVT), which may lead to
      pulmonary embolism (PE). In this population, numerous clinical trials have
      demonstrated comparable efficacy between dalteparin and fixed-dose UH for DVT
      prophylaxis. Dalteparin has a predictable dose response and can be administered
      as a standard single daily subcutaneous dose for all patients. In therapeutic
      doses, dalteparin does not alter coagulation tests and therefore does not require
      routine laboratory monitoring, in contrast with adjusted-dose UH. Bleeding risks
      with dalteparin are comparable with and possibly less than those associated with
      UH. Preliminary studies suggest that dalteparin may be effective for other
      indications, including DVT prophylaxis for hip replacement surgery and the
      treatment of DVT and PE. Comparative cost-effectiveness data are not yet
      available. CONCLUSIONS: Dalteparin is the second LMWH to receive approval by the
      Food and Drug Administration. Dalteparin is indicated for prophylaxis against DVT
      in patients undergoing abdominal surgery. Clinical studies have shown that single
      daily doses of dalteparin provide a safe and effective alternative to fixed-dose
      UH therapy. Additional studies are needed to determine the cost-effectiveness of
      dalteparin compared with UH and other LMWHs.

PMID- 9034423
TI  - Antibiotic-associated hepatitis: update from 1990.
AB  - OBJECTIVE: To review the literature on the recent available evidence of
      antibiotic-associated acute liver injury. DATA SOURCES: All published articles
      from January 1990 to July 1995 were extracted from the monthly updated HEPATOX
      database. Additional articles were found using MEDLINE, EMBASE, and PASCAL
      searches. Hepatic injuries associated with antituberculous, antimycotic,
      antiviral, antiprotozoal, and antiseptic compounds were excluded form this
      review. STUDY SELECTION: As the amount of literature was large, only case
      reports, series and epidemiologic data were used. Results from clinical trials
      were reviewed only when other information was available. DATA EXTRACTION:
      Original articles were reviewed to select relevant material. Information
      regarding the clinical description, histologic features, severity, outcome, and
      possible risk factors was extracted. Data on incidence were provided by
      epidemiologic studies or spontaneous reporting to regulatory agencies. DATA
      SYNTHESIS: Antibiotic-associated acute injury is rare, with an incidence not
      exceeding 1 case 10,000 users for most drugs. Among beta-lactams,
      amoxicillin/clavulanic acid and penicillinase-resistant penicillins are
      associated with predominant and sometimes protracted cholestasis. The hepatotoxic
      potential of all available erythromycin salts is confirmed, and recent evidence
      suggests that roxithromycin could be added to the list of antibiotic-induced
      liver injury. Among fluoroquinolones, only ciprofloxacin has been associated with
      serious hepatitis. Trimethoprim/sulfamethoxazole-induced hepatitis often
      reported, but trimethoprim alone also appears as a possible cause of acute liver
      injury. Finally, acute bile duct injuries and ductopenia have been described with
      several antibiotics. CONCLUSIONS: The most important recent information is the
      possibility of protracted liver cholestasis with bile duct injuries induced by
      several antibiotics, particularly penicillinase-resistant penicillins, and the
      identification of new potentially hepatotoxic antibiotics, namely, roxithromycin,
      ciprofloxacin, and trimethoprim.

PMID- 9034424
TI  - Nonnarcotic analgesics: prevalence and estimated economic impact of toxicities.
AB  - OBJECTIVE: To review and compare the risks of nonnarcotic analgesic toxicities in
      adults and estimate the relative healthcare costs of these toxicities, since
      direct comparison of costs is not possible. DATA SOURCES: A MEDLINE search of the
      literature from 1969 to 1995 was used to identify pertinent data. Additional
      references were identified from articles obtained in the search. Information was
      obtained from prospective, retrospective, controlled, and uncontrolled studies;
      case reports; and review articles. DATA EXTRACTION: Estimates of annual US costs
      of toxicities were extrapolated and synthesized from data from diagnosis-related
      groups, published information about the incidence of toxicity, or local data.
      DATA SYNTHESIS: Chronic use of nonsteroidal antiinflammatory drugs (NSAIDs) is
      associated with a high incidence of acute renal toxicity and gastrointestinal
      toxicity. The most common problems associated with acetaminophen use are
      hepatoxicity after acute problems ingestion of large doses (> 10 g) or habitual
      use of smaller doses (< 4 g), particularly in alcoholic patients, and chronic
      analgesic nephropathy. Aspirin use is associated with a high incidence of
      gastrointestinal and acute renal toxicity in certain patient groups. Available
      data suggest that acetaminophen, used intermittently, remains the nonnarcotic
      analgesic of choice in many patient populations, including those with impaired
      renal function, gastrointestinal disease, and bleeding disorders. Estimated
      annual US costs associated with the toxicities of acetaminophen (excluding
      hepatotoxicity), aspirin (acute upper gastrointestinal bleeding only), and NSAIDs
      (excluding non-upper gastrointestinal hemorrhagic complications and
      hepatotoxicity) are about $51.5 million, $358.6 million, and $1.35 billion,
      respectively. CONCLUSIONS: Intermittent use of most nonnarcotic analgesics
      produces a small risk of chronic renal or hepatic toxicity. Gastrointestinal
      toxicity, especially upper gastrointestinal bleeding, remains a significant
      problem with NSAIDs and aspirin. Acetaminophen remains the nonnarcotic analgesic
      of choice for intermittent use by most patient groups. The toxicities associated
      with NSAIDs constitute about 72.6% of the total toxicities (costs $1.86 billion)
      caused by NSAIDs, acetaminophen, and aspirin.

PMID- 9034425
TI  - New approaches to using antiretroviral therapy for the management of HIV
      Infection.
AB  - OBJECTIVE: To review the changes that have occurred in the past 2 years in the
      management of HIV infection with antiretroviral agents by contrasting the 1994
      with the 1996 Guidelines. DATA SOURCES: Conference proceedings, clinical
      experience of the author and her colleagues, and English-language articles from
      the body scientific literature identified via MEDLINE, AIDSLINE, and Current
      Contents served as data sources. DATA SYNTHESIS: Current antiretroviral
      management strategies include movement away from using zidovudine monotherapy,
      institution of combination antiretroviral therapy earlier in HIV diseases, the
      use of newer agents such as lamivudine, protease inhibitors (i.e., saquinavir,
      ritonavir, indinavir), and nonnucleoside reverse transcriptase inhibitors (i.e.,
      nevirapine, delavirdine), prevention of vertical transmission with zidovudine,
      and use of HIV-1 RNA determinations (viral load) to guide the initiation and
      alteration of antiretroviral therapy. These strategies represent a dramatic
      change from the 1994 Guideline, which recommended zidovudine monotherapy in
      nonpregnant and pregnant individuals whose CD4 cell counts were less than 500
      cells/mm3, when many of the newer agents were not available and the assays to
      determine viral load were strictly investigational. CONCLUSIONS: The difference
      between the 1994 and 1996 Guidelines is substantial. It is likely that within a
      year's time, newer information on pathogenesis and antiretroviral agents in
      development will be known and further management strategies will need to be
      disseminated. Until then, the International AIDS Society--USA Guidelines for 1996
      should be followed as the standard of care.

PMID- 9034426
TI  - Octreotide or vasopressin for bleeding esophageal varices.
AB  - Acute bleeding due to esophageal varices continues to be a life-threatening
      complication of liver disease. Despite the availability of improved therapy,
      mortality continues to be high. Octreotide has been shown to be at least as
      effective as vasopressin in the treatment of bleeding varices, with fewer and
      less severe systemic adverse effects. In addition, octreotide has also been
      consistently associated with a decreased need for transfusions. Octreotide has
      been used safely in patients without serious cardiovascular disease when
      administered as a continuous intravenous infusion of 25 micrograms/h for 24 hours
      with or without an initial 100-micrograms bolus dose. Since these trials have
      used small numbers of patients, the ability to detect small but clinically
      important differences has been limited. Additional controlled trials comparing
      octreotide with the combination of vasopressin and nitroglycerin are needed to
      more clearly determine the efficacy and cost-effectiveness of therapy.
      Furthermore, the optimal dosage, duration, and route of administration of
      octreotide in the treatment of bleeding esophageal varices has yet to be
      determined.

PMID- 9034427
TI  - Octreotide in hyperinsulinism.
AB  - In a limited number of case reports in infants, octreotide raised the blood
      glucose concentrations and decreased glucose requirements sufficiently to avoid
      pancreatectomy. This response occurs in the presence of frequent feedings and
      diazoxide therapy, and lasts from 1 month to greater than 5 years. As expected,
      octreotide reduces growth indices such as growth factors and growth rate in short
      term assessment. However, an insufficient sample size, a lack of follow-up, and
      poor study design provide inconclusive data. Among the few case reports in adults
      with benign or malignant insulinoma, octreotide can significantly raise blood
      glucose concentrations. In long-term follow-up, octreotide has alleviated or
      reduced the frequency of hypoglycemic episodes for periods of 5 months to 2.5
      years. Octreotide was administered subcutaneously in regimens of 100-1500
      micrograms in three to four divided doses or as a continuous infusion. Continuous
      subcutaneous infusion may be attempted in patients intolerant to intermittent
      administration. Octreotide may worsen existing hypoglycemia as result of
      suppressing glucagon and growth hormone in the presence of unresponsive
      pancreatic hyperinsulinism. While the long-term effects of growth remain
      undetermined, current findings suggest octreotide may provide a reasonable
      addition or alternative to diazoxide in controlling symptoms of congenital
      hyperinsulinism. Octreotide may be useful in management of hypoglycemic symptoms
      in adult patients requiring medical treatment for insulinoma who are refractory
      or intolerant of diazoxide. Additional long-term studies are needed to address
      the cost effectiveness of octreotide therapy, identify patients most likely to
      respond, and determine the impact of octreotide on height.

PMID- 9034428
TI  - Intravenous immune globulin for inducing remissions in systemic lupus
      erythematosus.
AB  - The evidence supporting the use of long-term IVIG therapy to induce remissions in
      SLE is unimpressive. The single extant clinical study used an open-label design
      with 12 patients, no placebo control, and questionable statistical methodology.
      The lack of definitive clinical studies, however, is tempered by case reports
      documenting significant improvement and apparent lack of toxicity in patients
      with SLE treated with IVIG. Standard first-line therapy of active SLE should
      consist of nonsteroidal antiinflammatory drugs, followed by low-dose
      corticosteroids and antimalarial compounds. Second-line therapeutic alternatives
      are the cytotoxic agents methotrexate, azathioprine, or cyclophosphamide. IVIG's
      primary advantage over these conventional therapies is that, unlike
      immunosuppressant and cytotoxic drugs, IVIG has not been reported to increase the
      risk of opportunistic infections. Additionally, IVIG obviates the
      ovarian/testicular toxicity, hemorrhagic cystitis, and carcinogenicity caused by
      cyclophosphamide. However, IVIG therapy is extremely expensive. (Approximate
      average wholesale price is $1800 per dose for a 70-kg patient). Thus, IVIG
      treatment consisting of 0.4 g/kg/d for 5 consecutive days on a monthly basis
      should be reserved for patients with active SLE resistant to the first- and
      second-line therapies. While IVIG-induced acute renal failure is considered rare,
      the serious nature of this adverse event warrants close monitoring of blood urea
      nitrogen and serum creatinine during and several days after treatment.
      Preexisting renal dysfunction should be considered a relative contradiction.
      Further double-blind multicenter trials are warranted to determine the long-term
      safety, efficacy, and cost/benefit ratio of using IVIG in SLE.

PMID- 9034429
TI  - Clinical consequences of nonnarcotic analgesic use.
AB  - The accuracy of the economic analysis of the selected adverse events evaluated by
      McGoldrick and Bailie is questionable. The quantitative perspective on the
      economics of the adverse events associated with nonnarcotic analgesic use
      proposed by these authors is limited by the fact that they have combined data on
      over 30 different NSAIDs into a single value for comparison with two single
      entity agents: acetaminophen and aspirin. The relative prevalence of major organ
      system toxicities varies markedly among the NSAIDs, and this variance invalidates
      the use of a class conclusion approach. Their conservative incidence estimates,
      the lack of data in some areas (i.e., hepatic injury), and the exclusion of
      combination analgesics further limit the utility of their conclusions. However,
      it is difficult to argue authoritatively that the relative costs of toxicities
      associated with the three analgesic classes they reviewed are not representative.
      The ultimate question is, "What is the optimal analgesic for a given patient?"
      This question can be addressed only if one considers the underlying cause of
      pain, its chronicity/acuity, the patient's concurrent disease states, if any, and
      the potential for drug interactions with the patient's concomitant medications.
      McGoldrick and Bailie concluded on an economic basis that acetaminophen is the
      analgesic of choice for most patients, including those with impaired renal
      function. This recommendation is in agreement with those of the Analgesics and
      the Kidney Ad Hoc Committee of the National Kidney Foundation. It also would seem
      prudent to use acetaminophen as the first-line agent for those patients in whom
      aspirin and NSAID use should be avoided or used only with caution along with
      frequent monitoring of renal function, blood pressure, electrolytes, and/or
      coagulation status. Thus, there is little to no controversy in their
      recommendation to initiate treatment with acetaminophen. The authors, however,
      also suggested that switching patients from an NSAID to acetaminophen would
      result in significantly decreased costs and morbidity. These authors, however,
      did not address one key issue that impacts their economic analysis: the relative
      efficacy of acetaminophen and NSAIDs. If efficacy is similar, then the
      risk/benefit ratio and economic consequences would favor the use of
      acetaminophen. However, if many patients are receiving NSAIDs because they did
      not obtain pain relief with the use of acetaminophen, there would be neither
      rationale or likely benefit with a change in therapy to acetaminophen. Finally,
      McGoldrick and Bailie did not evaluate an issue that has perhaps the most far
      reaching consequence. Many OTC analgesics are currently marketed as combinations
      of aspirin, acetaminophen, salicylamide, or caffeine (Table 2). Although the
      intent of these combinations was [Table: see text] to enhance efficacy while
      minimizing adverse events, it is now apparent that at least concerning adverse
      events, the goal was not achieved. Therefore, in light of the markedly higher
      risk for renal injury with combination analgesics, these agents should be
      withdrawn from the marketplace. While some might argue that patient education is
      the key and that addition of an explicit warning on the label of OTC combination
      products should be an adequate intervention, this agreement is not supported by
      the Belgium experience. The removal of combination analgesics from the OTC
      marketplace could be accomplished by governmental action, such as the ban on
      phenacetin over 10 years ago. Alternatively, pharmacists could no longer sell
      these products and counsel patients on the rational use of OTC analgesics. The
      choice among single-entity agents could then be individualized on the basis of
      patient's current medical status and the adverse event profile of the available
      agents.

PMID- 9034430
TI  - Immediate action needed to improve labeling of prescription drugs for pediatric
      patients.

PMID- 9034431
TI  - Ciprofloxacin-induced delirium.

PMID- 9034432
TI  - Heparin-associated refractory bronchospasm.

PMID- 9034433
TI  - Amlodipine-induced acute intermittent porphyria exacerbation.

PMID- 9034434
TI  - Assay interaction between oxaprozin and phenytoin.

PMID- 9034435
TI  - Butalbital cross-reactivity to an Emit assay for phenobarbital.

PMID- 9034436
TI  - Azole resistance in yeasts.

PMID- 9034437
TI  - Peritoneal adhesions produced by oral tetracycline.

PMID- 9034438
TI  - Prolintane: a "masked" amphetamine.

PMID- 9034439
TI  - Your professional future could depend on the controversial policy options in the
      Pew Commission health care workforce regulation report.

PMID- 9034440
TI  - AORN's response to the Pew Taskforce on Health Care Workforce Regulation.

PMID- 9034442
TI  - Laparoscopic distal pancreatectomy procedures in a rural hospital.
AB  - Laparoscopic surgical procedures are replacing traditional, more invasive
      surgical procedures--even in small, rural hospitals. During a period of 12
      months, the authors performed laparoscopic distal pancreatectomy procedures on
      two patients at a 20-bed hospital in North Dakota. Although surgeons in other
      countries have reported performing laparoscopic distal pancreatectomy procedures,
      this is the first published report of a US surgical team performing this
      procedure. Laparoscopic dissection of the distal pancreas allows preservation of
      patients' spleens, decreases postoperative pain and length of hospitalization,
      and permits patients to return to activities of daily living more quickly than
      with traditional open pancreatectomy procedures.

PMID- 9034443
TI  - Right thoracotomy approach to mitral valve surgical procedures.
AB  - The right thoracotomy approach to mitral valve surgical procedures allows
      surgeons to achieve excellent, rapid exposures of mitral annuli; facilitates the
      excision of diseased mitral valves; avoids injury to previously placed coronary
      artery bypass grafts; and aids surgeons with the insertion of valve prostheses.
      This approach is especially appropriate for patients with anatomic deviations
      (e.g., deep chest cavities, counterclockwise rotations of the heart) and hostile
      mediastina (i.e., previously opened mediastina with severe adhesions around the
      heart and posterior side of the sternum). This article discusses mitral valve
      disease, compares the right thoracotomy approach to median sternotomy, describes
      perioperative nursing care of patients undergoing mitral valve surgical
      procedures, and presents a case study.

PMID- 9034444
TI  - The significance and applications of informed consent.
AB  - Bringing well-informed patients to the OR is a challenge for all who participate
      in surgical patients' care. Although the issue of informed consent has been
      around for a long time, it was not until the latter half of the twentieth century
      that health care professionals and patients began to focus on informed consent as
      a central concern in health care. This article explains the roots of informed
      consent, the path it has traveled, and the importance that health care
      professionals, especially perioperative nurses, play in ensuring that patients
      are fully informed about their impending procedures.

PMID- 9034445
TI  - Development of a patient-centered preprocedure program.
AB  - Staff members at Blodgett Memorial Medical Center, Grand Rapids, Mich, developed
      and implemented a prototype for a new patient-centered preadmission testing (PAT)
      program. Using continuous improvement principles, an implementation team improved
      the existing PAT program by increasing patient satisfaction, reducing duplication
      of care and services, and avoiding delayed or canceled surgical procedures in the
      OR. The implementation team then designed a preprocedure learning process in
      which nurses performed patient assessments, coordinated information between
      departments, and made appropriate referrals.

PMID- 9034446
TI  - Building perioperative nursing research teams--Part I.
AB  - Perioperative nurses can use nursing research to acquire skills and knowledge to
      formulate independent judgments, make critical decisions, and become nurse
      scholars. This article, which is the first in a two-part series, describes the
      use of the model of experiential learning developed by David A. Kolb, PhD, to
      facilitate a team approach to perioperative nursing research. The second article
      in the series will focus on constraints and enablers to conducting and using
      nursing research in perioperative care settings and will provide suggestions for
      perioperative nurse managers to facilitate clinical research.

PMID- 9034447
TI  - Research utilization begins with learning to read research reports.

PMID- 9034448
TI  - Revised AORN recommended education standards for RN first assistant programs.
      Association of Operating Room Nurses.

PMID- 9034449
TI  - Patient outcomes: standards of perioperative care. Association of Operating Room
      Nurses.

PMID- 9034450
TI  - Where's WHALDO? In search of the wisest, health care alternative, long-term
      delivery organization.

PMID- 9034451
TI  - Surgical technologists on the move.

PMID- 9034454
TI  - Spectators in the OR.

PMID- 9034455
TI  - Assessment and management of sensory loss in elderly patients.
AB  - The increasing number of elderly patients undergoing surgical procedures is a
      reality. Providing nursing care to these patients presents a challenge throughout
      their perioperative experiences. Knowledge of normal age-related changes coupled
      with data from preoperative assessments allows perioperative nurses to plan,
      implement, and evaluate care of elderly surgical patients with sensory losses.

PMID- 9034456
TI  - Intraoperative respiratory complications.

PMID- 9034457
TI  - Clinical exemplar demonstrates critical thinking and assertive perioperative
      nursing intervention.

PMID- 9034458
TI  - Postpartum psychiatric disorder: who should be admitted and to which hospital?
AB  - OBJECTIVE: To review the question of whether an infant should be admitted to
      psychiatric services when a severe psychiatric disorder necessitates admission of
      the mother. METHOD: All available literature on mother-infant joint admission was
      reviewed and arguments for and against are summarised. RESULTS: Early reports
      favoured joint admission, then opinions changed, possibly for economic reasons.
      Recent thinking encompasses research data on (i) longer-term adverse effects of
      postnatal depression on the children, and (ii) the finding of psychological and
      psychiatric morbidity in many of the fathers. Joint admission to designated
      special units is valuable, but such facilities are only cost-efficient and
      effective if established as part of an appropriate broader plan for managing
      postpartum, psychiatric disorder. CONCLUSIONS: (1) Further research is needed to
      answer this question definitively. (2) Services at primary and secondary level
      require expansion. (3) All services should target the whole family.

PMID- 9034459
TI  - The role of lithium in the affective disorders.
AB  - The current status of lithium in the treatment of mania and recurrent affective
      disorder is considered. The potential usefulness of lithium in clinical practice
      is not being realised. There is a need for information on clinical monitoring
      practices in the community. Long-term effects of lithium on renal function are
      reviewed and guidelines for monitoring are presented.

PMID- 9034460
TI  - Religion, spirituality and psychiatry: conceptual, cultural and personal
      challenges.
AB  - OBJECTIVE: Recent psychiatric literature and contemporary sociopolitical
      developments suggest a need to reconsider the place of religion and spirituality
      in psychiatry. This paper was written with the aim of encouraging dialogue
      between the often antithetical realms of religion and science. METHOD: Material
      from psychiatric, sociological and religious studies literature was reviewed,
      with particular emphasis on New Zealand sources. RESULTS: Despite the
      secularising effects of science, the presence and influence of 'religiosity'
      remains substantial in Western culture. The literature emphasises the central
      importance of religion and spirituality for mental health, and the difficulty of
      integrating these concepts with scientific medicine. Psychiatric tradition and
      training may exaggerate the 'religiosity gap between doctors and patients. In New
      Zealand, the politically mandated bicultural approach to mental health demands an
      understanding of Maori spirituality. CONCLUSIONS: Intellectual, moral and
      pragmatic arguments all suggest that psychiatry should reconsider its attitude to
      religion and spirituality. There are many opportunities for research in the
      field. Psychiatry would benefit if the vocabulary and concepts of religion and
      spirituality were more familiar to trainees and practitioners. Patients would
      find better understanding from psychiatrists, and fruitful interdisciplinary
      dialogue about mutual issues of 'ultimate concern' might ensue.

PMID- 9034461
TI  - Approaches to measuring quality of life and their relevance to mental health.
AB  - OBJECTIVES: This paper describes the 'sociological' and health-related approaches
      to the measurement of quality of life and aims to describe their major findings,
      shortcomings and potential uses with mental health problems. METHOD: The
      literature is selectively reviewed to illustrate the major developments and
      conclusions. RESULTS: Despite the lack of an accepted definition of quality of
      life, sociological approaches have repeatedly shown in general populations, the
      mentally ill and the elderly that subjective assessments are more influential in
      determining expressions of happiness, wellbeing and life satisfaction than are
      the objective circumstances of a person's life. This supports the use of
      subjective judgements as the basis for quality-of-life determinations..
      CONCLUSIONS: The quality-of-life approaches can help to answer a broad range of
      questions of interest to psychiatry. Health-related quality-of-life approaches
      are potentially useful methods of demonstrating the impact of mental illness and
      the benefit of interventions. Further work is required to determine whether the
      commonly used measures are sensitive to change.

PMID- 9034462
TI  - Access to firearms and the risk of suicide: a case control study.
AB  - OBJECTIVE: This study examined the association between access to a firearm and
      risk of suicide in a consecutive sample of individuals who had made serious
      suicide attempts. METHOD: The study used a case control design in which a sample
      of 197 individuals who died by suicide and 302 individuals who made medically
      serious suicide attempts was contrasted with 1028 randomly selected community
      control subjects. RESULTS: Suicide attempts by gunshot accounted for 1.3% of all
      serious suicide attempts (with non-fatal outcome) and 13.3% of suicides. However,
      among those making serious suicide attempts, gunshot had a high rate of fatality
      (83.3%). While access to a firearm was associated with increased risks that
      gunshot would be chosen as the method of suicide attempt (OR = 107.9; CI = 24.8
      469.5), this access was not associated with significant increases in the risk of
      suicide (OR = 1.4; CI = 0.96-1.99). CONCLUSIONS: For this sample, access to a
      firearm was not associated with a significant increase in the risk of suicide,
      although such access was associated with an increased probability that gunshot
      would be chosen as the method of suicide attempt.

PMID- 9034463
TI  - Tourette's syndrome in the year 2000.
AB  - OBJECTIVE: To examine the current status of knowledge of Tourette's syndrome (TS)
      and to highlight those areas of research that are most likely to have the most
      significant advances in the next few years into the 21st century. METHOD: Index
      Medicus was consulted from its beginning in 1885 until 1964 (inclusive), looking
      initially under the title 'tics' and subsequently under 'Tourette's Disorder'.
      From 1965 and the advent of MEDLINE, a search was performed looking for
      'Tourette's'. A chronological examination of TS in the medical literature is
      presented. Some issues surrounding Huntington's Disease (HD) research are
      pertinent to TS and may serve as a guide in the future direction of TS research;
      these issues have been identified and illustrated in the context of TS. Where
      relevant, other medical disorders are also commented on. RESULTS: There has been
      a steady increase in the volume of TS literature since 1885, with a marked
      increase since 1980, changing in focus from a psychological to a neurobiological
      viewpoint. Current areas of interest include genetics, comorbid
      psychopathologies, neuroimaging, treatments, epidemiology and educational
      considerations. Issues raised by HD and other movement disorders such as
      Parkinson's Disease (PD) are predictive testing, gene therapy and neural
      transplants. CONCLUSIONS: The year 2000 is likely to herald a significant
      increase in our knowledge of the genetics and neuroimaging of TS, with new
      developments in therapy. A broadening of awareness of TS among health workers and
      teachers in particular is likely to increase the number of diagnosed patients
      and, hence, new challenges will be posed to existing resources for health and
      educational provision.

PMID- 9034464
TI  - Rehabilitation of frontal/executive impairments in schizophrenia.
AB  - OBJECTIVE: A relatively high prevalence of deficits in cognitive flexibility,
      working memory and planning ability has been reported in schizophrenia patients.
      The objective was to develop a rehabilitation training program in an attempt to
      improve these specific cognitive functions. METHODS: The deficits in cognitive
      flexibility, working memory and planning ability were interpreted as reflecting
      executive cognitive processing impairments secondary to prefrontal neural system
      dysfunction. Following the 'process specific' approach, it was considered
      important to develop tasks that hypothesised the exercise of these cognitive
      abilities and the more molecular information processes thought to be fundamental
      to these abilities. Care was taken to ensure that all tasks involved the practice
      of processes thought to activate frontal/prefrontal neural systems. Attentional,
      visual, verbal, conceptual, motor and fine motor tasks were considered important
      for each process area in order to involve as many functional modalities as
      possible. RESULTS: A program comprising cognitive shift, working memory and
      planning modules was developed. Conducted over 11 weeks, four modules were of 2
      weeks' duration, and the fifth of 3 weeks' duration. Four individual 1 hour
      training sessions were conducted each week. Core elements of the modules are
      described. CONCLUSION: Consisting predominantly of pencil and paper information
      processing exercises, all of the training exercises are presented in the volumes
      of the Frontal/Executive Program. The program appears to be user-friendly with
      therapists now successfully delivering the program, in its entirety, to
      schizophrenia patients. Should future studies replicate preliminary findings of
      improved neurocognitive performance following training with the program, such
      findings would have important implications for the treatment of schizophrenia.

PMID- 9034465
TI  - Competence and the elderly patient with cognitive impairments.
AB  - OBJECTIVE: The purpose of this paper is to discuss the assessment of competence
      in the elderly, focusing particularly on individuals with cognitive impairments.
      METHOD: An analysis of autonomy forms the basis of an ethical discussion which
      attempts to modify the existing concept of competence. RESULTS AND CONCLUSION: A
      discussion of the factors which influence competence is presented including
      variations in situation, task and degree of risk. A critical analysis of four
      standards of competence is presented, leading to a discussion of the standards
      which can most successfully promote self-determination in elderly patients.
      Finally, three classes of competence are suggested which extend the criteria of
      competence to patients to cognitive deficits.

PMID- 9034466
TI  - The psychiatric care of people with intellectual disabilities: the perceptions of
      consultant psychiatrists in Victoria.
AB  - OBJECTIVE: This study was undertaken to establish the perceptions of
      psychiatrists regarding the care of people of intellectual disabilities. METHOD:
      A 28-item self-administered questionnaire was developed, piloted and sent on two
      occasions to 467 psychiatrists who receive the newsletter of the Victorian branch
      of the Royal Australian and New Zealand College of Psychiatrists. The
      questionnaire incorporated a Likert scale to document the opinions of the
      respondents. RESULTS: A response rate of 51.1% was achieved. The respondents
      indicated that, in their opinion, people with intellectual disabilities receive a
      poor standard of care in the inpatient and community setting. To improve this
      situation, the following strategies were recommended: the development of improved
      liaison between services; improved training for all personnel who provide
      services to people with intellectual disabilities; the development of greater
      resources; and support for professionals working in the area. The study also
      indicates that there is a core group of very interested psychiatrists who are
      currently practising and that people with intellectual disabilities are accessing
      private psychiatric services. In addition, the results suggest that diagnostic
      overshadowing is not a major barrier to psychiatric assessment, and that
      disorders which were presumed to be commonly overlooked by doctors (such as
      depression) are in fact frequently being diagnosed. CONCLUSIONS: Despite some
      positive findings, the majority of psychiatrists who responded held major
      concerns about the situation of people with intellectual disabilities. To improve
      the care provided to these people, it is recommended that these concerns are
      addressed by the psychiatric profession and responsible government departments in
      conjunction with university departments of psychiatry.

PMID- 9034467
TI  - A prospective study of childhood emotional and behavioural problems in Port
      Pirie, South Australia.
AB  - OBJECTIVE: To describe the extent to which emotional and behavioural problems
      experienced by 5-year-old children living in or around Port Pirie, South
      Australia, persisted when the children were aged 11-12 years. METHOD: Childhood
      emotional and behavioural problems were identified at the age of 5 years using
      Child Behaviour Checklists completed by mothers. When the children were aged 11
      12 years, problems were identified using checklists completed by mothers,
      children and teachers. RESULTS: Attention problems, aggressive behaviour and
      anxious/depressed problems were the most persistent problems over this period of
      the children's lives. In general, the strongest relationship over time occurred
      when reports were obtained from mothers on each occasion. A weaker relationship
      existed between earlier mother-reported problems and later teacher-reported
      problems, while the relationship between mother-reported problems and later self
      reported problems occupied an intermediate position. CONCLUSION: The course of
      problems among children in Port Pirie appeared similar to that previously
      reported for children in Holland and North America. To better understand the
      aetiology of psychiatric disorders and to plan for effective interventions, more
      information is needed about the natural course of childhood emotional and
      behavioural disorders in Australia.

PMID- 9034468
TI  - Psychiatric disorder among adolescents in custody.
AB  - OBJECTIVE: To determine the diagnostic breakdown and comorbid patterns of 100
      consecutive cases referred for psychiatric consultation at juvenile detention
      centres, and to compare diagnoses according to gender and legal status. METHOD:
      Diagnoses were made at the time of an initial semi-structured clinical interview,
      and reviewed after follow-up. RESULTS: There was an appreciable minority of young
      offenders with non-behaviour disordered diagnoses as well as a large number with
      conduct disorder and substance abuse. Conduct disorder and affective disorder
      were most influential on adjustment in the community. CONCLUSION: Psychiatric
      initiatives are essential in the management of serious young offenders.

PMID- 9034469
TI  - Mandatory reporting of child abuse: is it in the best interest of the child?
AB  - OBJECTIVE: To set out correctly the law on mandatory reporting of child abuse in
      each Australian jurisdiction and New Zealand; to argue that all patients should
      be forewarned of the limits of confidentiality in respect of this; and to discuss
      the question of whether mandatory reporting is in the best interests of the
      child. METHOD: Discussion of statutes mandating reporting of child abuse, duty of
      confidentiality, the experience of mandatory reporting and failure to comply,
      forewarning of limits of confidentiality, arguments for and against mandatory
      reporting, and alternatives. RESULTS: Not all mental health providers comply with
      the law, for reasons both altruistic and non-altruistic. Although ethical codes
      for Australian mental health providers do not require forewarning, ethical
      practice would seem to do so. CONCLUSIONS: Mandatory reporting statutes now in
      force are not necessarily in the best interests of the child. An important
      clinical implication of the law is that considerations should be given to
      forewarning patients.

PMID- 9034470
TI  - Legal rights and responsibilities of adolescents and staff in Victorian Child and
      Adolescent Mental Health Services.
AB  - OBJECTIVES: The aim of the paper is to clarify the legal rights of adolescent
      patients, guardians and staff in Victorian Child and adolescent Mental Health
      Services (CAMHS). Victorian CAMHS have now been 'gazetted' and can admit patients
      on an involuntary basis under the amended Mental Health Act 1986 (MHA). The MHA
      applies equally to young people under the age of 18 years, which has raised some
      confusion about who has the right to consent to treatment. METHOD: Staff of CAMHS
      inpatient units have recently posed questions to the Victorian chief
      psychiatrist. These have included clarification of when the MHA may be
      appropriately used for adolescents, what is the clinician's duty of care, how to
      assess young people's capacity to consent to treatment, how to manage some
      patient groups, and what is the role of the courts in treatment decisions. The
      author provides a view on each of these matters, based on recent literature and
      confirmed by legal opinion. RESULTS: Some matters of fact are presented and
      advice is provided. CONCLUSIONS: Services must seek the informed consent of
      guardians and adolescents and, for those young people with major psychiatric
      disorders who require treatment and are unable to consent, the amended MHA
      provides clearer direction for the use of involuntary treatment. Where units
      offer admission to provide assessment and stabilisation, a clear explanation
      about the treatment goals, and the role of restraint and medication in managing
      behaviour is essential at the outset of the admission process.

PMID- 9034471
TI  - The status of ethics education in Australasian psychiatry.
AB  - OBJECTIVE: To determine to what extent ethics is taught and how it is taught to
      psychiatrists-in-training across Australasia. METHOD: Anonymous mail-out survey
      of training directors. RESULTS: The questionnaire was completed by 23 of 25
      training directors (response rate = 92%) who reported on 625 trainee
      psychiatrists. Individual one-to-one case supervision was adopted by 96% of the
      programs for teaching ethics; formal teaching in seminars or lectures was chosen
      as the second most common method in 70% of programs. Topics most commonly taught
      in formal seminars were so taught in only 70% of programs or less. CONCLUSION: A
      uniform curriculum in psychiatric ethics is needed. The results are discussed in
      relation to identified needs for improvement.

PMID- 9034472
TI  - Descriptors of depression: the importance of agreed definitions.
AB  - OBJECTIVE: We suggest that some descriptors and criteria of depressive features
      lack clarity or are overinclusive, with definitional limitations and vagaries in
      rating options, leading to variable ratings of similar items across differing
      measures as well as cloudy interpretation of positive ratings. METHOD: We
      illustrate these limitations by reference to two items: 'guilt' and 'distinct
      quality of mood'. RESULTS: We note problems emerging from confounded and
      imprecise definitions. CONCLUSIONS: We emphasise the need for definitions of
      depressive descriptors possessing greater specificity.

PMID- 9034473
TI  - Defining the personality disorders: description of an Australian database.
AB  - OBJECTIVE: We seek to improve the definition and classification of the
      personality disorders (PDs) and derive a large database for addressing this
      objective. METHOD: The paper describes the rationale for the development of a
      large set of descriptors of the PDs (including all DSM-IV and ICD-10 descriptors,
      but enriched by an additional 109 items), the design of parallel self-report (SR)
      and corroborative witness (CW) measures, sample recruitment (of 863 patients with
      a priori evidence of personality disorder or disturbance) and preliminary
      descriptive data. RESULTS: Analyses (particularly those comparing ratings on
      molar PD descriptions with putative PD dimensions) argue for acceptable
      reliability of the data set, while both the size of the sample and the
      representation of all PD dimensions of interest argue for the adequacy of the
      database. CONCLUSIONS: We consider in some detail current limitations to the
      definition and classification of the PDs, and foreshadow the analytic techniques
      that will be used to address the key objectives of allowing the PDs to be
      modelled more clearly and, ideally, measured with greater precision and validity.

PMID- 9034474
TI  - Chronic fatigue syndrome and dieting disorders: diagnosis and management
      problems.
AB  - OBJECTIVE: This paper illustrates the importance of conducting an initial and
      ongoing psychiatric assessment of patients with chronic fatigue syndrome in order
      to diagnose dieting disorders. The diagnostic issues and management problems of
      three case vignettes, two with anorexia nervosa and one with bulimia nervosa, are
      described. METHOD: The treatment response of dieting disordered patients is
      generally prolonged after a previous diagnosis of chronic fatigue syndrome has
      been made and the patient and family favour a disease diagnosis. RESULTS: Several
      management problems arise and family members may also be reluctant to accept a
      dieting disorder diagnosis. CONCLUSIONS: Early detection of dieting disorders by
      adequate screening and assessment is necessary so that a significant reduction in
      morbidity may occur.

PMID- 9034475
TI  - The aversiveness of specific emotional states associated with binge-eating in
      obese subjects.
AB  - OBJECTIVE: The aim of this study was to examine the hypothesis that non-purge
      related binge-eating in obesity is maintained by a 'trade-off' in which a highly
      aversive emotional state is exchanged for a less aversive state. METHOD: Ninety
      eight obese binge-eaters meeting the DSM-IV criteria for binge-eating disorder
      were contrasted with 65 non-binge-eating controls on their perceived distress
      associated with negative mood states usually experienced before and after binges.
      RESULTS: Binge-eaters reported significantly greater distress and lower tolerance
      of negative mood compared to controls. Furthermore, when compared with controls,
      binge-eaters reported that emotions typically reported before binges (e.g. anger)
      were more aversive than those reported after (e.g. guilt). CONCLUSIONS: These
      results were interpreted as supporting the 'trade-off' theory and have
      implications for the treatment of binge-eating disorder.

PMID- 9034476
TI  - Assessing the prevalence of eating disorders in an Australian twin population.
AB  - OBJECTIVE: This paper examines the prevalence of disordered eating in a female
      Australian twin population aged between 28 and 90 years in 1993. METHOD: In two
      waves of data collection, the eating behaviour of 3869 female twins was first
      assessed in 1988-1989 by self-report questionnaire and then in 1992-1993 with a
      telephone interview, using the Semi-Structured Assessment for the Genetics of
      Alcoholism interview. RESULTS: It was found that about 0.4% of the women have a
      lifetime prevalence of anorexia nervosa and 1.8% of the group have suffered from
      bulimia nervosa. The incidence of bulimia nervosa but not anorexia nervosa was
      markedly higher for those women under 45 (2.3% bulimia nervosa) than for those
      women 45 years or older. Furthermore, one in three women have at some stage in
      their life used some extreme method of weight control. CONCLUSIONS: The levels of
      bulimia nervosa and anorexia nervosa found are commensurate with those found in
      smaller studies in Australia and other parts of the world. The finding of
      widespread use of extreme weight control methods is of concern as this behaviour
      is a well-recognised precursor to more serious eating disorders.

PMID- 9034477
TI  - Group treatment for postpartum depression: a pilot study.
AB  - OBJECTIVE: There are few reports on the efficacy of treatment programs for women
      with postpartum depression, despite the long-term nature of this disorder. This
      study describes a pilot evaluation of a treatment program with educational,
      social support and cognitive-behavioural components. METHOD: Ten women with
      persistent depression originating in the postpartum period were offered a 10-week
      group treatment program and compared to a wait-list control group. RESULTS:
      Following treatment, a significant improvement in depression was demonstrated on
      the Edinburgh Post-Natal Depression Scale, Beck Depression Inventory, and Profile
      of Mood States. Several common factors in women suffering from postpartum
      depression were also identified, as were drop-out characteristics. CONCLUSION:
      These results are encouraging and suggest that a cognitive-behavioural group
      program might be effective as a treatment for depression in the postpartum
      period. However, further detailed studies are required to conform this pilot
      study.

PMID- 9034478
TI  - Denied pregnancy.
AB  - OBJECTIVE: To review the literature on the topic of denied pregnancy and present
      a case study that illustrates some salient points. CLINICAL PICTURE: A 21-year
      old woman was unaware of her pregnancy until she went into labour, at which time
      she went into a state of panic. She delivered a dead baby. TREATMENT: She was
      interviewed over the 5 days following delivery and referred for psychiatric
      assessment. She was discharged when cleared of serious psychiatric illness.
      OUTCOME: At follow-up she was well but haunted by recollections of the delivery.
      She was referred for further counselling. CONCLUSIONS: Denial of pregnancy is
      more common than realised. It is a heterogeneous condition associated with
      different coping styles and psychiatric diagnoses. Early testing for pregnancy is
      recommended in young women with nausea, weight gain and menstruation-like
      bleeding.

PMID- 9034479
TI  - The dangers of dextropropoxyphene.
AB  - OBJECTIVE: Dextropropoxyphene is a commonly used analgesic despite its high
      toxicity in overdose and potential for abuse and dependence. This case report
      highlights these dangers. CLINICAL PICTURE: The case of a female who was addicted
      to dextropropoxyphene as an alternative to other opioids is described. Its use in
      high doses with other psychotropic agents resulted in adverse health effects.
      TREATMENT: The patient was treated with methadone and psychosocial interventions.
      OUTCOME: The patient reduced her drug use and experienced improved physical
      health and psychosocial functioning. CONCLUSIONS: Caution is needed when
      prescribing dextropropoxyphene because of its adverse effects compared with
      equally efficacious analgesics.

PMID- 9034481
TI  - Lithium-induced neurotoxicity at serum lithium levels within the therapeutic
      range.
AB  - OBJECTIVE: To report the occurrence of lithium-induced neurotoxicity and
      extrapyramidal symptoms at serum lithium levels within the therapeutic range.
      CLINICAL PICTURE: On two occasions, a 73-year-old patient presented with symptoms
      of lithium-induced neurotoxicity and extrapyramidal symptoms when her serum
      lithium levels were within the therapeutic range. TREATMENT AND OUTCOME: Both
      lithium-induced neurotoxicity and extrapyramidal symptoms resolved when lithium
      was withdrawn. CONCLUSION: Even when serum lithium levels are within the
      therapeutic range, lithium-induced neurotoxicity may occur. Patients on
      neuroleptics and the elderly in particular may be more vulnerable to these side
      effects.

PMID- 9034480
TI  - A patient with mania and photoconvulsive epilepsy.
AB  - OBJECTIVE: To describe a young patient who had a comorbidity of mania and
      photoconvulsive epilepsy. CLINICAL PICTURE: This patient presented with a
      clinical picture of mania which proved difficult to treat until an EEG revealed
      the presence of photoconvulsive epilepsy. TREATMENT: Treatment with haloperidol
      and lithium was unsuccessful but the addition of carbamazepine produced a
      dramatic response. Haloperidol was stopped and the patient maintained on lithium
      and carbamazepine. OUTCOME: A successful outcome was achieved with carbamazepine
      and the patient has remained well on this treatment for 2 years. CONCLUSIONS: The
      authors postulate that there may be an association between photoconvulsive
      epilepsy and mania, perhaps on a kindling basis. The literature pertaining to the
      psychiatric aspects of photoconvulsive epilepsy is reviewed.

PMID- 9034482
TI  - Neuroleptic malignant syndrome and malignant hyperthermia.

PMID- 9034483
TI  - Clozapine-induced agranulocytosis.

PMID- 9034484
TI  - The diagnosis of neuroleptic malignant syndrome revisited.

PMID- 9034485
TI  - Somatoform disorders.

PMID- 9034486
TI  - Cannabis use.

PMID- 9034487
TI  - Outdated diagnoses, managed care and our own future.

PMID- 9034488
TI  - Critique of the psychology of self: an update.

PMID- 9034489
TI  - Osteodystrophy in a kitten.

PMID- 9034490
TI  - Granular cell tumour in the bronchus of a horse.

PMID- 9034491
TI  - Atresia of the external acoustic meatus in a dog.
AB  - A 3 year old, female great Dane with atresia of the right external ear canal had
      recurrent episodes of ear pain. Radiography revealed absence of air in the right
      external acoustic meatus, thickened bone of the right tympanic bulla and
      increased radiodensity of the chamber of the bulla. Total ear canal ablation and
      lateral bulla osteotomy were performed. The superficial portion of the external
      ear canal was absent and the deeper segment of the vertical ear canal began as a
      blunt ended cartilage tube. A patent lumen in the existent portion of the
      external ear canal and the tympanic bulla contained wax, hair and exfoliated
      squames. The tympanic membrane was not intact. No bacteria were cultured from the
      contents of the external and middle ear. The dog responded well to surgery and
      was free of pain 11 months later. Failure to surgically correct atresia of the
      ear canal in young dogs may allow the accumulation of cellular and sebaceous
      debris with subsequent involvement of the middle ear in an inflammatory response.

PMID- 9034492
TI  - Compensated immune mediated haemolytic anaemia in a dog.
AB  - A dog which presented with anorexia and fever was found to have strong IgG
      Coombs' positive immune mediated haemolysis but only marginal anaemia. The
      abnormalities detected included marked spherocytosis, polychromasia and mild
      hyperbilirubinaemia. The major presenting signs disappeared after glucocorticoid
      therapy. Compensated idiopathic immune mediated haemolysis was diagnosed.

PMID- 9034493
TI  - Sheep deaths after accidental ingestion of gypsum fertiliser.

PMID- 9034494
TI  - Multiple striate keratotomy: a treatment for corneal erosions caused by
      epithelial basement membrane disease.
AB  - OBJECTIVE: To study the efficacy of multiple striate keratotomy for the treatment
      of persistent corneal erosions suspected to be caused by primary corneal
      epithelial basement membrane disease. DESIGN: A retrospective study. ANIMALS: 16
      dogs, three cats and one Australian dingo. PROCEDURE: A technique called multiple
      striate keratotomy was used to treat twenty animals suffering from persistent
      corneal erosions. RESULTS: All persistent corneal erosions healed with only one
      treatment. Most cases healed within 2 weeks. One case developed a second erosion
      in the same eye but in a different position to the original erosion. CONCLUSIONS:
      Multiple striate keratotomy is a safe, effective and well tolerated technique for
      the treatment of persistent corneal erosions thought to be caused by corneal
      epithelial basement membrane disease.

PMID- 9034495
TI  - Australian veterinarian awarded the Nobel Prize for Medicine.

PMID- 9034496
TI  - Persistent efficacy of abamectin and doramectin against gastrointestinal
      nematodes of cattle.
AB  - OBJECTIVE: To assess the persistent activity of injectable formulations of
      abamectin and doramectin against gastrointestinal nematodes of cattle. DESIGN:
      Controlled slaughter study assessing residual efficacy. PROCEDURE: Nematode-free
      calves were treated with abamectin or doramectin (each at a dose of 200
      micrograms/kg) and infections then induced with repeated doses of infective
      larvae of Trichostrongylus axei, Haemonchus placei, Ostertagia ostertagi and
      Cooperia species. The duration of challenge ranged from 14 to 28 days. The calves
      were slaughtered at either 38/39 or 45/46 days after the treatments and nematodes
      recovered from the gastro-intestinal tract. RESULTS: Significant reductions in
      numbers of O ostertagi occurred for both abamectin and doramectin treatments (>
      93%) relative to counts in untreated calves, when challenge was administered up
      to 21 days after treatment. For T axei and Cooperia spp significant reductions
      occurred when the challenge occurred for 14 days after treatment (99%). Although
      differences from untreated animals were not significant, the results for H placei
      suggested high efficacy (> 85%) for up to 21 days for doramectin and up to 28
      days for abamectin. CONCLUSIONS: There was no significant difference between
      abamectin and doramectin for any parasite at any challenge point, indicating that
      there is equivalent persistent activity of doramectin and abamectin against
      important gastrointestinal nematodes of cattle.

PMID- 9034497
TI  - Efficacy of ivermectin controlled-release capsules for the control and prevention
      of nasal bot infestations in sheep.
AB  - OBJECTIVE: To investigate the therapeutic and prophylactic efficacy of an
      ivermectin controlled-release capsule against nasal bots (Oestrus ovis) in sheep.
      DESIGN: Trial 1--A pen study with controls. Trial 2--A field study with controls.
      ANIMALS: Trial 1--Forty Merino wethers with natural infestations of nasal bot
      were used. Trial 2--One hundred nasal bot-free wethers were used. PROCEDURE:
      Trial 1--Ten randomly selected animals were slaughtered and the heads split and
      examined to confirm bot infestation. Fifteen animals were allocated to untreated
      controls and 15 to treatment with a controlled-release capsule delivering
      ivermectin at > or = 20 micrograms/kg/day for 100 days. Twenty-nine days after
      treatment the sheep were killed and examined for nasal bots. Trial 2--Nasal bot
      free sheep were allocated to two groups of 45 animals. One group was untreated
      the other sheep were treated with capsules as above. The sheep were grazed as a
      single group exposed to natural challenge from O ovis. Ninety days after
      treatment the animals were slaughtered and examined for nasal bot infestation.
      RESULTS: Trial 1--Live O ovis larvae were recovered from 60% of control sheep. No
      live larvae were collected from treated sheep. Trial 2--Forty-one percent of
      untreated sheep harbored nasal bot infestations. No live larvae were collected
      from any treated animal. CONCLUSION: Treatment with a single ivermectin
      controlled release capsule was 100% effective against existing infestations of O
      ovis and as a prophylactic treatment for this parasite.

PMID- 9034498
TI  - Age-related differences in collagen crimp patterns in the superficial digital
      flexor tendon core region of untrained horses.
AB  - OBJECTIVE: To measure collagen fibril crimp angles and lengths as well as
      collagen fibril mass-average diameters in central and peripheral regions of the
      superficial digital flexor tendon of wild horses, to ascertain any age-related
      changes in either region in the absence of imposed galloping exercise. DESIGN:
      Measurements from a random cull of wild horses. SAMPLE POPULATION: Superficial
      digital flexor tendon samples were taken from 23 wild horses ranging in age from
      two to ten years. PROCEDURE: Horses were divided into 'young' (< 5 years, n =
      10), 'middle-aged' (5 to < 10 years, n = 9) and 'old' groups (10+ years, n = 4)
      and the mean crimp angle, mean crimp length and collagen fibril mass-average
      diameter calculated for the central region, and for the peripheral region of each
      group. Differences between groups and regions were analysed using two-tailed t
      tests. RESULTS: The crimp angle for the central region was found to decrease with
      age, so that in old horses it was smaller than that for the tendon periphery (P,
      0.05). The crimp angle for the latter region did not alter significantly with
      age. Crimp period lengths and collagen fibril mass-average diameters did not show
      significant changes with age in either region. CONCLUSIONS: Reduction of the
      crimp angle in the core of the superficial digital flexor tendon occurs normally
      with age, as tendons of older animals would have undergone a higher number of
      loading cycles. It is possible that athletic training increases the frequency
      and/or the magnitude of high loading cycles experienced by the tendon, and may
      accelerate and worsen the normal load-related ageing process in the superficial
      digital flexor tendons of young performance horses, particularly in the central
      regions where lesions usually occur.

PMID- 9034499
TI  - Epidemiological investigation of the buller steer syndrome (riding behaviour) in
      a western Canadian feedlot.
AB  - OBJECTIVE: To describe the buller steer syndrome in a Western Canadian feedlot.
      DESIGN: a retrospective study. ANIMALS: 78,445 male cattle that entered a 24,00
      head feedlot in western Canada from 1991 to 1993. PROCEDURE: All cattle were
      given a hormonal growth promotant containing 20 mg oestradiol benzoate and 20 mg
      progesterone within 24 h of arrival at the feedlot. A 'buller' was a steer that
      was observed at daily pen checking to be ridden persistently by pen mates or had
      evidence of having been persistently ridden by pen mates. At the completion of
      the feeding period, animal health records for bullers were collected and
      analysed. RESULTS: The prevalence of bullers in the total population was
      2,139/78,445 (2.7%, range per pen 0 to 11.2%). The prevalence of bullers
      increased with increasing weight and age. The relapse risk after first treatment
      (three days in the feedlot hospital plus treatment for concurrent disease) was
      30% on average (27 to 35%). Individual records from 9,734 yearling steers that
      entered the feedlot in 1991 and 1992 showed that bullers were significantly (P <
      0.05) heavier at processing than non-bullers. Bullers occurred as a point source
      epidemic with a cause occurring soon after cattle arrived at the feedlot and were
      mingled into pen grous. This gave a 'days on feed' distribution. The peak
      incidence of bullers occurred much sooner after arrival and dropped off much
      quicker in older cattle. The daily incidence of bullers was temporal, but was not
      related to season of the year, weather condition of any other feedlot management
      practice. It was related to the seasonal arrival of cattle at the feedlot, their
      age at entry to the feedlot and the post arrival occurrence of bullers.
      Reimplantation with hormonal growth promotants and castration of intact bulls did
      not produce an epidemic of bullers. CONCLUSIONS: The findings of this study
      support the theory that bullers are the result of agonistic interactions, which
      occur concurrent with the establishment and maintenance of a social hierarchy
      with pens of feedlot cattle.

PMID- 9034500
TI  - Characterisation of Australian isolates of Actinobacillus capsulatus,
      Actinobacillus equuli, Pasteurella caballi and Bisgaard Taxa 9 and 11.
AB  - OBJECTIVE: The objective of this work was to perform a comprehensive phenotypic
      characterisation of 16 isolates of bacteria previously identified as
      Actinobacillus equuli. DESIGN: The 16 isolates that had been obtained from
      Australian animals--15 from horses and one from a rabbit--were compared with
      reference strains of A equuli, A capsulatus, Pasteurella caballi and Bisgaard
      Taxa 9 and 11. RESULTS: The characterisation study demonstrated that only nine of
      the isolates were A equuli. The other isolates were identified as A capsulatus
      (the isolate from rabbit), P caballi (one isolate), Bisgaard Taxon 11 (two
      isolates) and Bisgaard Taxon 9 (one isolate). The final two isolates could not be
      assigned to any recognised species or taxa. CONCLUSION: This study has
      highlighted the importance of a complete characterisation of Actinobacillus-like
      organisms isolated from horses and rabbits. The study represents the first time
      that A capsulatus, P caballi and Bisgaard Taxa 9 and 11 have been recognised as
      being present in Australia.

PMID- 9034501
TI  - Failure of passive transfer in foals: incidence and outcome on four studs in New
      South Wales.
AB  - OBJECTIVE: To determine the regional incidence and effectiveness of treatment of
      failure of passive transfer (FPT) in foals. DESIGN: A study of disease incidence.
      ANIMALS: Eighty-eight foals and 57 mares from four studs in the practice area of
      the Rural Veterinary Centre were tested. PROCEDURE: Foals were tested for their
      serum IgG and total serum protein (TSP) concentration within the first 72 hours
      of life. Colostrum was collected from mares and specific gravity determined. FPT
      and partial failure of passive transfer (PFPT) of immunoglobulins was diagnosed
      when serum IgG concentrations were < 4 g/L and 4 to 8 g/L respectively. Owners of
      foals diagnosed with FPT were offered treatment with 1 to 2 L plasma (TSP > 70
      g/L); 9 (64%) of the affected foals were treated. RESULTS: Fourteen foals (16%)
      had FPT whereas 15 (17%) had PFPT. There were significant differences between the
      mean TSP concentration in foals with FPT (42.6 +/- 4.2 g/L), PFPT (48.1 +/- 3.9
      g/L) and those acquiring adequate passive immunity (58.9 +/- 5.5 g/l) (p < 0.01).
      Sixteen (29%) mares had pre-suck colostral specific gravity < 1.060 and 12 (71%)
      foals raised by these mares had FPT or PFPT. The incidence of severe disease
      (categorised by a sepsis score > 11, positive culture of bacteria from blood or
      disease requiring hospitalisation) in all foals in the first 2 months of life was
      10%. However, none of the nine foals with FPT that received plasma experienced
      severe disease. In contrast, foals with PFPT had an increased susceptibility to
      severe disease (p < 0.001) when compared with normal foals. CONCLUSION: Treatment
      of foals with FPT may reduce the subsequent incidence of severe disease. Pre-suck
      colostral specific gravity and foal TSP may be used to predict the likelihood of
      FPT and PFPT. Even though the number of foals studied is small the results
      highlight the importance of optimal management practices in reducing the
      incidence of FPT and disease associated with this process.

PMID- 9034502
TI  - Veterinary education. Comments stimulated by the Pew Report.

PMID- 9034503
TI  - Hypertrophic osteopathy in an alpaca.

PMID- 9034504
TI  - Comparison of the infectivity of Babesia bovis, Babesia bigemina and Anaplasma
      centrale for cattle after cryopreservation in either dimethylsulphoxide (DMSO) or
      polyvinylpyrrolidone (PVP).

PMID- 9034505
TI  - Wastage in the Australian thoroughbred racing industry: a survey of Sydney
      trainers.

PMID- 9034506
TI  - Eastern barred bandicoot recovery; the role of the veterinarian in the management
      of endangered species.

PMID- 9034507
TI  - Ceroid-lipofuscinosis in miniature Schnauzer dogs.

PMID- 9034508
TI  - Chemical quandary.

PMID- 9034532
TI  - Neuropsychiatric implications of basal ganglia dysfunction.

PMID- 9034533
TI  - Association of the D2 dopamine receptor A1 allele with alcoholism: medical
      severity of alcoholism and type of controls.
AB  - D2 dopamine receptor (DRD2) A1 allele frequency was determined in alcoholics of
      varying medical severity from three different inpatient settings and in various
      controls. A1 frequency was .15 in 68 alcoholics in a detoxification unit (group
      A), .19 in 90 alcoholics in a rehabilitation unit (group B), and .31 in 43
      alcoholics in a gastroenterology unit (group C). Group C had a higher A1
      frequency than group B (p = .045) or group A (p = .005) alcoholics. In 46
      controls (group D), A1 frequency was .18. In subsets of these controls, A1
      frequency was .14 in 39 subjects with a negative family history (FH-) of
      alcoholism (group E), .06 in 34 subjects without previous hazardous alcohol
      consumption (group F), and .05 in 30 subjects with FH- and without previous
      hazardous alcohol consumption (group G). A1 frequency was significantly higher in
      group C alcoholics than group F (p = .0002) or group G (p = .0002) controls;
      however, no A1 frequency difference was found among group A alcoholics and any of
      the control groups. The severity of alcoholism and the type of controls used are
      important determinants of DRD2 A1 allele association with alcoholism.

PMID- 9034534
TI  - The dopamine D4 receptor gene (DRD4) is not associated with alcoholism in three
      Taiwanese populations: six polymorphisms tested separately and as haplotypes.
AB  - The dopaminergic system has been implicated in alcoholism but studies at the
      dopamine D2 receptor gene (DRD2), one of the five dopamine receptors, have not
      given a consistent picture of an association with alcoholism. We have now studied
      the dopamine D4 receptor gene (DRD4) using six polymorphisms, both separately and
      as haplotypes. Three groups of alcoholics from Taiwan (Atayal, Ami, and Han)
      diagnosed as having severe alcohol dependence using DSM-III-R criteria, together
      with nonalcoholics matched for gender, ethnic group, and geographic origin, were
      typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length
      polymorphism (RFLP) for all six polymorphisms. Three out of six markers are
      polymorphic in all three Taiwanese populations. Although the prevalence rates of
      alcoholism are remarkably different, no highly significant association of this
      locus with alcoholism was observed in any of the three groups whether the
      analysis considered genotype distributions or allele frequencies at the three
      polymorphic markers considered individually and as haplotypes. Neither is there
      any obvious pattern in the data that covaries with or hints at a relationship
      with the very different prevalences of alcoholism in the groups studied.
      Especially because the powerful, multi-site haplotype analysis was not
      statistically significant in any of the population samples, we conclude that
      there is no association of the DRD4 locus with alcoholism in Taiwanese
      populations.

PMID- 9034535
TI  - Electroencephalographic sleep correlates of episode and vulnerability to
      recurrence in depression.
AB  - The study of electroencephalogram (EEG) sleep in depressed patients before and
      after treatment with psychotherapy can distinguish episode-related and persistent
      biological features. With longitudinal follow-up, we can also assess whether EEG
      sleep measures are associated with recurrence of depression. In the current
      study, we examined EEG sleep during the depressed state and during symptomatic
      remission after treatment with interpersonal psychotherapy in 42 outpatients with
      major depression. Analyses included both visually-scored and computer-analyzed
      measures. Patients showed significant increases in sleep latency (p = .01) and
      rapid eye movement (REM) latency (p = .04) from baseline to remission, as well as
      a decrease in REM sleep percent (p = .03). Total delta EEG counts decreased from
      baseline to remission (p = .03), specifically in the second nonrapid eye movement
      (NREM) period (p = .03); as a result, the relative distribution of delta activity
      shifted toward sleep onset (i.e., increased delta sleep ratio; p = .03).
      Automated REM counts also decreased from depression to remission (p = .006).
      Compared to patients who remained well through one year of follow-up, those who
      suffered a recurrence of depression had less delta EEG activity at baseline and
      remission (p = .01), particularly in the lowest delta frequency band of 0.5-1.0
      Hz. Specific components of sleep (total delta activity, delta ratio, REM
      activity) constitute episode-related biological features. Other components
      (slowest delta activity) may represent vulnerability factors for recurrence.

PMID- 9034536
TI  - Changes in sleep architecture following chronic mild stress.
AB  - Chronic exposure to mild unpredictable stress causes subsensitivity to rewards
      (anhedonia). These effects are reversible by chronic treatment with
      antidepressant drugs, and have been proposed as an animal model of depression. In
      the present study, sleep architecture, particularly the rapid eye movement (REM)
      component, was mapped in rats following exposure to chronic mild stress. The
      study used a unique large scale automated sleep system to record and analyze the
      sleep signals from 32 rats simultaneously. The effects of stress on sleep were
      maximal following 21 days of stress, at which time the stressed animals
      demonstrated decreases in active waking and deep sleep, and disruptions of REM
      sleep. The changes in REM sleep included increases in the duration of and
      transitions into REM sleep over the sleep part of the sleep-wake cycle, and most
      importantly, a reduced latency to the onset of the first REM period. These sleep
      abnormalities, and in particular the decrease in REM latency, are consistent with
      those reported in endogenous depression. The results provide further support for
      the validity of the chronic mild stress paradigm as an animal model to study the
      mechanisms underlying endogenous depression.

PMID- 9034537
TI  - Dynamical analysis of schizophrenia courses.
AB  - In order to assess the working hypothesis that schizophrenia may be viewed as a
      nonlinear dynamical disease, we examined the long-term psychoticity dynamics of
      14 patients. The data consist of daily ratings of psychopathology observed for
      200 or more consecutive days in each patient. We implemented nonlinear dynamical
      analysis methods with a potential of being applicable even to relatively short
      and noisy time series: two different forecasting approaches combined with
      surrogate methods that allow statistical testing in each single case. The
      resulting classification of dynamics gives evidence that eight patients show
      nonlinear evolutions of symptom courses. Four cases can be modeled linearly, two
      as random processes. Thus, a larger proportion of the schizophrenic psychoses we
      studied shows nonlinear time courses. In this way the validity of the concept of
      dynamical diseases could be supported on statistical grounds in this important
      area of psychopathology. The nonlinear view-a low-dimensional nonlinear system
      generating psychotic symptoms--may provide the foundation for a more parsimonious
      theory of schizophrenia compared to traditional multicausal models. In several of
      the nonlinear cases we also observed the qualitative "fingerprint" of
      deterministic chaos: a decay of deterministic features of the course of disorder
      with time.

PMID- 9034538
TI  - Changes in emotional behavior produced by long-term amygdala kindling in rats.
AB  - The effects of long-term amygdala kindling on emotional behavior were
      investigated. In Experiment 1, rats received 99 basolateral amygdala, central
      amygdala, or sham stimulations. The rats in both kindled groups displayed more
      resistance to capture from an open field and more open-arm activity on an
      elevated plus maze than did the sham control rats. In Experiment 2, rats received
      either 20, 60, or 100 amygdala stimulations or sham stimulations. Compared to the
      sham controls, the kindled rats explored less during the first 30s in a novel
      open field, avoided the central area of the open field, resisted being captured
      from the open field, and engaged in more open-arm activity on the elevated plus
      maze. The magnitude of these effects was greatest in the 100-stim rats and least
      in the 20-stim rats. Together, these results suggest that long-term amygdala
      kindling in rats is a useful model for studying the emotionality associated with
      temporal lobe epilepsy.

PMID- 9034539
TI  - Changes in sensorimotor inhibition across the menstrual cycle: implications for
      neuropsychiatric disorders.
AB  - The startle reflex is inhibited when the starting noise is preceded 30-500 msec
      by a weak prepulse. "Prepulse inhibition" (PPI) is reduced in specific
      neuropsychiatric disorders characterized clinically by impaired inhibition of
      sensory, motor, or cognitive information. PPI is sexually dimorphic, with men
      exhibiting significantly more PPI than women. We examined possible neuroendocrine
      substrates for this sex difference in PPI. The startle reflex, and a measure of
      visuospatial priming, were measured in 10 men, and in 46 normal women at
      different points in their menstrual cycle. In women, PPI was significantly
      reduced in the luteal vs follicular phase of the menstrual cycle. This reduction
      in PPI was most notable during the period corresponding to midluteal elevations
      of both estrogen and progesterone. In a task of visuospatial priming, follicular
      phase women demonstrated a predominance of inhibition over facilitation, but this
      pattern reversed across the menstrual cycle.

PMID- 9034540
TI  - Effects of repeated cocaine administration on sensory inhibition in rats:
      preliminary data.
AB  - We have recently reported that acute administration of cocaine to rats alters
      their sensory inhibitory capacity as tested in a paired click paradigm (S1/S2).
      Whether such acutely induced changes are persistent, is not known. In order to
      shed some light on the degree of spontaneous reversibility of cocaine-induced
      decreased sensory inhibition, rats were tested immediately after cocaine
      administration and 9 days after cessation of cocaine exposure. Six rats received
      cocaine HCl 20 mg/kg intraperitoneally and six rats received normal saline for 5
      consecutive days. The amplitudes of the S1 responses were significantly decreased
      in the cocaine animals during the injection days only, but not 9 days later. Two
      measures of sensory inhibition were employed, S2/S1 x 100 amplitude ratio and S1
      S2 amplitude difference. The ratio measure indicated a significant decrease in
      inhibitory capacity in the cocaine group during the injection days, and remained
      significantly decreased 9 days after cessation of cocaine administration. The
      data suggest that repeated cocaine administration can induce persistent deficit
      in the ability of the rat's brain to inhibit incoming irrelevant sensory stimuli.

PMID- 9034541
TI  - Psychiatric manifestations and magnetic resonance imaging in HIV-negative
      neurosyphilis.
AB  - Neurosyphilis can mimic virtually any psychiatric disorder. Since there are no
      studies measuring the relationship between its psychiatric manifestations and
      neuroradiological findings, we performed magnetic resonance imaging (MRI) on 20
      newly diagnosed patients with neurosyphilis and 20 healthy volunteers. MRI
      abnormalities occurred in 13 neurosyphilis patients. These included foci of
      increased signal intensity of T2-weighted images, and generalized cerebral
      atrophy. Two control subjects showed minor focal changes. In the neurosyphilis
      patients, frontal lesions showed statistically significant associations with the
      overall degree of psychiatric morbidity as measured by the brief psychiatric
      rating scale (p < 0.05). Temporo-parietal lesions showed a near significant
      association with cognitive impairment as measured by the Mini mental-state
      examination (p = 0.06). Atrophy measures correlated significantly with cognitive
      impairment. The results suggest that the site of brain lesions may be important
      in determining the nature of the psychiatric symptoms in neurosyphilis.

PMID- 9034542
TI  - Neurophysiological changes associated with psychiatric symptoms in HIV-infected
      individuals without AIDS.
AB  - HIV-1 infection may be complicated by a number of psychopathological conditions.
      While organic mental disorders, such as HIV-related psychosis and dementia, are
      late manifestations, mood disorders may occur during both asymptomatic and
      symptomatic stages of infection. The possible impact of brain involvement due to
      neurotropism of HIV-1 has not been investigated systematically in these latter
      conditions. The psychiatric caseness of HIV-seropositive individuals without AIDS
      and seronegative controls was assessed using a standardized clinical interview
      (Present State Examination). A comparison was made between individuals with and
      without psychiatric caseness using clinical, neuropsychological, and
      neurophysiological assessments. An increased prevalence of current psychiatric
      illness was found in subjects with early symptomatic HIV infection compared to
      those with asymptomatic infection and controls. This could not be attributed to
      psychiatric history, as well as to clinical and immunological markers of HIV
      infection, however, psychiatric caseness in early symptomatic infection was
      associated with marked neurophysiological changes, detectable by quantitative
      electroencephalography. Altogether, this study provided preliminary evidence that
      psychiatric symptoms in symptomatic but not asymptomatic HIV infection may be
      associated with subtle brain involvement preceding the immunological and
      neurocognitive impairment characteristic for AIDS.

PMID- 9034543
TI  - Gastrointestinal absorption of aluminum is increased in Down's syndrome.
AB  - Individuals with Down's Syndrome (DS) develop the neuropathological features of
      senile dementia of the Alzheimer's type (SDAT) by early middle age. Because of
      recent evidence that gastrointestinal (GI) aluminum (Al) absorption is increased
      in patients with SDAT, and that Al may contribute to associated neuropathological
      changes, we have investigated the GI uptake of Al in patients with DS by two
      methods. The first measured the absorption of 27Al at concentrations associated
      with antacid use, in the presence of citrate, using atomic absorption
      spectrometry. There was no difference between basal blood concentrations of 27Al
      in 15 DS subjects (36-46 years) and 15 age-matched controls. The mean increase in
      27Al blood concentrations 60 minutes after the dose of Al was four times greater
      in the DS group than in controls (p < 0.001). The second measured GI absorption
      of 26Al under normal dietary conditions using accelerator mass spectrometry. With
      26Al the mean Al absorption in DS subjects (n = 5) exceeded that of controls (n =
      4) by a factor of 6 (p < 0.02). Although the mechanisms of enhanced absorption
      are unknown, the data indicate that similar abnormalities in the GI handling of
      Al occur in both SDAT and DS suggesting that it may be advisable to minimize
      dietary exposure to Al in subjects at risk of developing Alzheimer-type
      pathology.

PMID- 9034544
TI  - Lack of association of a functional catechol-O-methyltransferase gene
      polymorphism in schizophrenia.

PMID- 9034545
TI  - Electroencephalographic photic driving in patients with schizophrenia and
      depression.

PMID- 9034546
TI  - Elevated frontal lobe cytosolic choline levels in minimal or mild AIDS dementia
      complex patients: a proton magnetic resonance spectroscopy study.

PMID- 9034547
TI  - Bone mineral density and L-thyroxine treatment in rapidly cycling bipolar
      disorder.

PMID- 9034553
TI  - Fibrin sealant: current and potential clinical applications.
AB  - There are few well-controlled studies of the clinical efficacy of fibrin sealant,
      defined by lives saved or reduced need for blood transfusions. Evaluation of
      fibrin sealant in trauma situations, e.g. liver laceration, has been difficult to
      perform. Only recently has fibrin sealant been actively promoted by US
      manufacturers as a commercially valuable alternative to the relatively
      inexpensive crude bovine thrombin and cryoprecipitate that are in current use.
      Regulatory agencies and manufacturers are aware that patients in the USA are
      receiving a suboptimal form of fibrin glue since cryoprecipitate is not virally
      inactivated and has a variable fibrinogen concentration. In addition, bovine
      thrombin is not regulated with respect to factor V content or any other
      impurities. During the past year regulatory agencies, together with manufacturers
      and clinicians, have begun to define clinically valid endpoints for efficacy of a
      commercially prepared fibrin sealant. These may include improvement in hemostasis
      compared with a placebo or agents considered to be 'standard of care'. Thus, the
      regulatory agencies may be willing to consider studies in animals that
      demonstrate efficacy as well as surrogate endpoints, such as reduced factor
      concentrate requirements in patients with severe hemophilia requiring dental
      extraction. As fibrin sealant becomes available in a liquid and potentially in a
      bandage form, it may also become an essential matrix for recombinant factors that
      can affect endothelial function.

PMID- 9034554
TI  - Colloid determination of fibrin network permeability.
AB  - The effects of polymers, dextran and polyvinylpyrolidone (PVP) and of albumin on
      the permeability of thrombin-induced fibrin networks developed in plasma were
      examined. Both PVP and dextran increased the network permeability and turbidity
      and increased the fibrin fibre thickness. The effect was molecular weight
      dependent. Derivation of the dimensionless permeability (permeability/fibre
      radius2) indicated that the increase in network permeability was mainly from
      altered arrangement of fibres and not from increased fibre thickness. The effects
      of albumin on network structure were similar to those of the polymers. Scanning
      electron microscopy of networks developed in plasma under the influence of
      dextran and poloxamer 188 showed fibres with increased thickness and a coarse
      nodular appearance. There was an increased tendency for fibres to be aggregated
      into clumps. It is suggested that during polymerization fibrin fibres and fibrin
      polymerization intermediaries behave as colloidal particles. Attractive forces
      between the particles are generated by soluble macromolecules such as plasma
      proteins or polymers. Attractive forces increase the thickness of fibrin fibres
      and induce a more permeable arrangement of the fibres in the network. The most
      likely colloidal mechanism is depletion flocculation. This would account for (1)
      the molecular weight dependence and concentration dependence of the effects of
      macromolecules, (2) the effects of macromolecules which do not bind to fibrin,
      (3) the effects of the surfactant poloxamer 188. Depletion flocculation may be a
      significant mechanism for biological regulation of fibrin network permeability by
      non-specific macromolecules such as soluble proteins or fibrin intermediaries.

PMID- 9034555
TI  - The influence of factor VIII on measurement of activated protein C resistance.
AB  - Activated protein C resistance (APCR) has proved to be a frequent finding in
      association with thrombosis. The majority of patients with APCR have been found
      to be homozygous or heterozygous for the polymorphic variant factor V Q506
      (factor V Leiden; FVQ506). However a small number of patients have APCR as
      assessed by functional tests but do not possess the FVQ506 polymorphism. Some of
      these cases are due to the presence of a lupus type anticoagulant but in this
      report we demonstrate that the remainder are almost entirely (nine out of ten)
      associated with an elevated level of FVIIIc. Spiking experiments in normal
      patient plasma and venous occlusion tests demonstrated that elevation of the
      FVIIIc results in a reduced APCR ratio and shortening of the APTT. Variation in
      FVIIIc, in conjunction with other factors, may therefore explain the variable
      phenotype associated with FVQ506 and the phenomenon of thrombosis associated APCR
      in the absence of FVQ506. We conclude that FVIIIc as well as FVQ506 should be
      taken into account when assessing thrombotic risk. APCR, elevated FVIIIc and
      shortened APTT have all been previously identified with an increased risk of
      thrombosis. It follows that resistance to APC may arise from a number of factors
      and is in itself a risk factor for thrombosis. The net effect of these factors is
      assessed in the functional test for APCR and it may be premature therefore to
      replace functional tests for APCR with DNA analysis alone.

PMID- 9034556
TI  - Hemostatic changes after thrombolytic therapy with saruplase (unglycosylated
      single-chain urokinase-type plasminogen activator) and urokinase (two-chain
      urokinase-type plasminogen activator).
AB  - Urokinase, or two-chain urokinase-type plasminogen activator (tcu-PA), is an
      effective thrombolytic agent. Its single-chain precursor (scu-PA), unlike tcu-PA,
      is able to selectively activate fibrin-bound plasminogen. The induced clot lysis
      is amplified by plasmin-triggered conversion of scu-PA to tcu-PA. The aim of our
      study was to compare the hemostatic effects of recombinant unglycosylated scu-PA,
      INN saruplase, and urokinase, at doses considered optimal (80 mg saruplase and 3
      million units urokinase) in patients with acute myocardial infarction, within 6 h
      of onset of pain. Complete sample sets from more than 230 patients in each
      treatment group have been analyzed. The median hemostatic changes caused by
      saruplase and urokinase were virtually identical indicating that saruplase is
      converted early in vivo to its active tcu-PA derivative with the dose regimen
      used. Fibrinogen degradation products were higher for saruplase with a maximum at
      2h. They rose markedly after saruplase from 0.43 mg/l at 0 h to a maximum of 160
      mg/l at 2 h, whereas the increase after urokinase (from 0.45 mg/l to 89.0 mg/l)
      was significantly smaller (P < 0.001).

PMID- 9034557
TI  - Simvastatin inhibits myointimal hyperplasia following carotid artery injury in
      cholesterol-fed rabbits.
AB  - The effect of simvastatin, a potent inhibitor of 3-hydroxy 3-methylglutaryl
      coenzyme A reductase (HMG-CoA reductase) was evaluated in an experimental model
      of myointimal hyperplasia in cholesterol-fed rabbits. Myointimal hyperplasia was
      induced by an air-drying injury of the left carotid artery followed by a 2%
      cholesterol diet for 14 days. A 2-week oral treatment with simvastatin (6
      mg/kg/day, p.o.) significantly lowered the circulating levels of cholesterol and
      triglycerides (41% and 49% inhibition respectively) as well as the low density
      lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol
      levels. Simvastatin also strongly affected the uptake of cholesterol in the
      arteries occurring as a consequence of vascular injury (44% inhibition, P <
      0.001). Morphometric analysis revealed that both the intima and the media areas
      increased substantially 2 weeks after the lesion and showed a considerable smooth
      muscle cell accumulation in the neointima together with the presence of numerous
      foam cells. A 16-day oral treatment with simvastatin strongly reduced smooth
      muscle cells hyperplasia occurring in both the media and the intima following
      deendothelialization (19% and 60% inhibition respectively) suggesting that
      simvastatin may be a useful inhibitor of restenosis which occurs following
      vascular injury.

PMID- 9034558
TI  - Plasma fibronectin in overweight men and women: correlation with serum
      triglyceride levels and serum cholinesterase activity.
AB  - When compared with 67 age- and sex-matched normal weight control subjects, the 71
      overweight patients displayed obviously higher levels of plasma fibronectin. For
      a similar body mass index (BMI) the 16 overweight men younger than 45 years had a
      significantly (P < 0.01) higher plasma fibronectin level (455 +/- 99.3 mg/l; mean
      +/- SD) than the 16 age-matched overweight women (351 +/- 105 mg/l) while there
      was no significant difference between the 22 overweight men (446 +/- 89.2 mg/l)
      and the 17 overweight women (475 +/- 111 mg/l) older than 45 years. Particularly
      high plasma fibronectin levels were noted in the five women with upper body
      (android) obesity. Plasma fibronectin was positively correlated with BMI, serum
      triglyceride concentration, plasma fibrinogen and serum cholinesterase activity.
      It is considered that metabolic disturbances related to upper body obesity may
      lead to an enhanced hepatic secretion of VLDL and of several plasma proteins
      including fibronectin.

PMID- 9034559
TI  - Heparin-induced thrombocytopenia with thrombotic complications during
      prophylactic treatment with low-molecular-weight heparin.
AB  - Heparin-induced thrombocytopenia is very uncommon with low-molecular-weight
      heparin, especially when given for prophylaxis of venous thromboembolism. In two
      of the four published cases, with thrombotic complications, thrombocytopenia may
      have been related to cross-reactivity between unfractionated heparin and low
      molecular-weight heparin. We report one patient who received low-molecular-weight
      heparin for prophylaxis against venous thromboembolism without any previous
      injection of unfractionated heparin, and experienced thrombocytopenia with
      thrombotic complications. Heparin-induced thrombocytopenia was confirmed by
      several laboratory assays. This observation emphasizes the need for platelet
      count monitoring during low-molecular-weight heparin therapy.

PMID- 9034560
TI  - Soluble P selectin in peripheral vascular disease: relationship to the location
      and extent of atherosclerotic disease and its risk factors.
AB  - Circulating levels of the adhesion molecule P-selectin (CD62P) are increased in
      the plasma of patients with atherosclerosis, but its relationship to the
      anatomical location of symptomatic disease or extent of symptomatic disease is
      unknown. The influence of the risk factors for atherosclerosis on soluble P
      selectin is also unclear. To clarify these questions we analysed plasma samples
      from 170 patients with symptomatic peripheral vascular disease and 119
      asymptomatic controls who were, as a group, age- and sex-matched. Soluble P
      selectin (ELISA) was increased in 83 patients with symptomatic disease of the
      iliac and/or femoral arteries alone (P < 0.05, ANOVA) but not in 37 patients with
      symptomatic carotid artery disease alone compared with controls. Soluble P
      selectin was equally raised in 120 patients with disease at one arterial site and
      in 50 patients with disease at two or more arterial sites (both P < 0.05)
      compared with controls. Smoking and atherosclerosis were both independent
      predictors of raised soluble P-selectin. We conclude that increased soluble P
      selectin may have value as a marker of peripheral vascular disease of the iliac
      and/or femoral arteries in group comparisons only, as the poor discrimination and
      wide variation of data make comparisons at the individual level difficult.

PMID- 9034561
TI  - Plasma levels of activated FVII in various diseases.
AB  - Plasma activated factor VIIa (FVIIa) levels were measured in various diseases
      using mutant tissue factor (TF). FVIIa levels in thrombotic patients and patients
      with idiopathic thrombocytopenic purpura were significantly higher than those in
      healthy control subjects. The plasma FVIIa levels in thrombotic patients treated
      with warfarin were similar to those of control subjects. The plasma FVIIa levels
      in pregnant women and patients with systemic lupus erythematosus, infection or
      malignancies were high. However, the levels in patients with disseminated
      intravascular coagulation (DIC) were not significantly increased. DIC patients
      are in a severe hypercoagulable state, and exhibit severe consumption of
      coagulation factors. The slightly increased FVIIa level in the DIC patients
      observed is probably considered to be caused by consumption of coagulation
      factors. The plasma FVIIa level was poorly correlated with other hemostatic
      parameters except for protein C in our analysis of all cases. In the analysis of
      DIC and thrombotic patients treated without warfarin, the plasma FVIIa level was
      negatively correlated with TF antigen. Plasma FVIIa levels might reflect
      hypercoagulability in thrombotic diseases, and a normalized FVIIa level in
      patients with thrombotic diseases should be considered to be associated with DIC.

PMID- 9034562
TI  - Rapid detection of factor V: Q506 mutation using whole blood protein C
      resistance.

PMID- 9034563
TI  - Pathology and immunocytochemistry of a kuru brain.
AB  - We report here results of modern staining techniques including anti-prion protein
      (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old
      male who died from kuru in 1967. Brain suspensions transmitted disease to
      chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the
      polymorphic codon 129. Histology shows neuronal loss, spongiform change, and
      astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of
      frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus,
      and are accentuated in middle and deep cerebral cortical layers. PrP accumulates
      as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition
      is maximal in parasagittal and interhemispheric areas of frontal, central and
      parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques
      are prominent in the striatum, thalamus, and granular layer of cerebellar cortex.
      Meticulous examination reveals only rare "florid" plaques with surrounding
      vacuolation. We conclude that 1) pathology including immunomorphology of PrP
      deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob
      disease although plaques are unusually prominent and widespread; 2) kuru does not
      share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease
      variant recently reported in the UK and France; 3) topographic prominence of PrP
      deposition parallels that of spongiform change and/or astrogliosis.

PMID- 9034564
TI  - Kuru: forty years later, a historical note.

PMID- 9034565
TI  - Tropical diseases: a historical perspective.

PMID- 9034566
TI  - Cerebral malaria.
AB  - Malaria infection of the Central Nervous System (CNS) can cause a severe
      neurological syndrome termed Cerebral Malaria (CM). The central neuropathological
      feature of CM is the preferential sequestration of parasitised red blood cells
      (PRBC) in the cerebral microvasculature. The level of sequestration is related to
      the incidence of cerebral symptoms in severe malaria. Other neuropathological
      features of CM include petechial hemorrhages in the brain parenchyma, ring
      hemorrhages and Durck's granuloma's. Immunohisto-chemical and electron microscopy
      studies have shown widespread cerebral endothelial cell activation and
      morphological changes occur in CM, as well as focal endothelial cell damage and
      necrosis. The immune cell response to intravascular sequestration appears to be
      limited, although activation of pigment-phagocytosing monocytes is a late
      feature. The mechanisms by which PRBC cause coma in malaria remain unclear. In
      vitro parasitised erythrocytes bind to endothelial cells by specific, receptor
      mediated interactions with host adhesion molecules such as ICAM-1, whose
      expression on cerebral endothelial cells is increased during CM as part of a
      systemic endothelial activation. Induction of local neuro-active mediators such
      as nitric oxide and systemic cytokines like TNF alpha may be responsible for the
      rapidly reversible symptoms of the coma of CM. The recent cloning of the parasite
      ligand PfEMP-1, thought to mediate binding to host sequestration receptors,
      promises further insight into the relationship between patterns of sequestration
      and the incidence and pathogenesis of coma in cerebral malaria.

PMID- 9034567
TI  - Free-living, amphizoic and opportunistic amebas.
AB  - Amebas belonging to the genera Naegleria, Acanthamoeba and Balamuthia are free
      living, amphizoic and opportunistic protozoa that are ubiquitous in nature. These
      amebas are found in soil, water and air samples from all over the world. Human
      infection due to these amebas involving brain, skin, lung and eyes has increased
      significantly during the last 10 years. The epidemiology, immunology,
      protozoology, pathology, and clinical features of the infections produced by
      these protozoa differ strikingly. Infection by the pathogenic Naegleria fowleri
      is acquired by exposure to polluted water in ponds, swimming pools and man-made
      lakes. Raised temperatures during the hot summer months or warm water from power
      plants facilitate the growth of N. fowleri. N. fowleri is a thermophilic ameba
      that grows well in tropical and subtropical climates. The CNS infection, called
      Primary Amebic Meningoencephalitis (PAM), produced by N. fowleri is characterized
      by an acute fulminant meningoencephalitis leading to death 3-7 days after
      exposure. Victims are healthy, young individuals with a history of recent water
      related sport activities. The portal of entry is the olfactory neuroepithelium.
      The pathologic changes are an acute hemorrhagic necrotizing meningoencephalitis
      with modest purulent exudate, mainly at the base of the brain, brain-stem and
      cerebellum. Trophozoites can be seen within the CNS lesions located mainly around
      blood vessels. Thus far 179 cases have been reported; 81 in the USA alone.
      Balamuthia mandrillaris and several species of Acanthamoeba are pathogenic
      "opportunistic" free-living amebas which cause Granulomatous Amebic Encephalitis
      (GAE) in humans and animals. GAE is an infection, usually seen in debilitated,
      malnourished individuals, in patients undergoing immunosuppressive therapy for
      organ transplants and in Acquired Immunodeficiency Syndrome (AIDS). The
      granulomatous component is negligible, particularly in immunocompromised
      individuals. Pathologically these amebas produce a patchy, chronic or subacute
      granulomatous encephalitis with the presence of trophozoites and cysts. The
      portal of entry is probably through the respiratory tract or an ulceration of the
      skin reaching the CNS by hematogenous spread. As of October 1, 1996, 166 cases
      (103 due to Acanthamoeba and 63 due to Balamuthia) of GAE have been reported from
      around the world. Of these 103 cases due to Acanthamoeba (72 have been reported
      in the USA alone, > 50 in AIDS). It is well known that several species of
      Acanthamoeba can also produce, chronic sight threatening ulceration of the cornea
      called Acanthamoeba keratitis (AK), mostly in contact lens wearers or in
      individuals with minor corneal abrasions. Hundreds of cases of AK have been
      documented world wide.

PMID- 9034568
TI  - Trypanosomiasis.
AB  - African (sleeping sickness) and American (Chagas' disease) trypanosomiasis,
      caused by protozoa of the family Trypanosomatidae, are diseases that are endemic
      in parts of Africa and Latin America, respectively. Physicians in developed
      countries may occasionally see cases because of extensive travel and immigration
      from endemic countries. Although neurological involvement is common in both, its
      incidence and clinical presentation differ considerably. African trypanosomiasis,
      caused by subspecies of Trypanosoma brucei (T b rhodesiense, T b gambiense), is
      transmitted by the tsetse fly and causes meningoencephalitis, in which somnolence
      is a prominent feature. Parasites may reach the brain parenchyma through the
      choroid plexus or the Virchow Robin spaces. American trypanosomiasis, caused by
      Trypanosoma cruzi is transmitted by reduviid bugs. While lesions in the central
      nervous system are not prominent, except in the reactivated forms which occur in
      immunodeficient patients, the peripheral nerve, mainly the autonomic nervous
      system, is frequently involved, leading to the cardiomegaly and the digestive
      megaviscera. Congenital infections may also occur. In this paper we give an
      account of the epidemiology, clinical presentation and pathological features of
      these two protozoal infections based on human and experimental studies of both
      the central and peripheral nervous system.

PMID- 9034569
TI  - Fungal infections.
AB  - Fungal infections have increased in frequency in the last decades because of the
      growing number of immunocompromised patients who survive longer periods of time
      than in the past, the widespread use of immunosuppressive drugs, a large aging
      population with increased numbers of malignancies, and the spread of AIDS.
      Although fungi are present everywhere, some mycoses predominate in the tropics,
      not only in view of warm temperature and humid climate, which favor their growth,
      but also because of inadequate hygienic and working conditions brought about by
      poverty. Mycotic diseases in the brain are usually secondary to infections
      elsewhere in the body, usually the lungs, less often from other extracranial
      sites, and in the vast majority of the cases spread via blood circulation. Only
      occasionally they result from direct extensions from infections of the sinuses or
      bone, and less frequently from prosthetic heart valves. Candida may be endogenous
      in origin, inhabiting the digestive tract. Most fungi cause basal meningitis or
      intraparenchymal abscesses. Direct extension from the cribriform plate cause
      necro-hemorrhagic lesions in the base of the frontal lobe. Although fungi are
      common in our environment, few are pathogenic. In this paper mycotic infections
      are divided into opportunistic and pathogenic; although most of the latter have
      also been described in immunosuppressed patients, some of those caused by
      opportunistic organisms, have also occurred in the absence of predisposing
      factors.

PMID- 9034570
TI  - Bacterial infections.
AB  - The organisms that produce bacterial infections of the nervous system in tropical
      regions are similar to those existing in the rest of the world. However, because
      of poor socio-economic conditions in the former areas, preventing the
      implementation of appropriate prophylactic and therapeutic measures, the
      incidence and course of these diseases may vary. In this paper the
      neuropathological appearances of the main bacterial diseases are reviewed and the
      main differences between those occurring in developed and developing countries
      emphasized. Despite great efforts by governments and communities, tuberculosis
      still remains a scourge in many countries and leprosy has not been eradicated
      from earth. Earlier optimism that antibiotics could finally put an end to
      syphilis have been dashed and the disease still persists. Moreover, the explosion
      of AIDS not only has produced a recrudescence of many of these diseases, but has
      also changed their clinical and pathological presentation.

PMID- 9034571
TI  - Neuroschistosomiasis.
AB  - Schistosomiasis is an infection caused by digenetic trematode platyhelminths of
      the genus Schistosoma. These blood flukes use man and other mammals as definitive
      hosts and aquatic and amphibious snails as intermediate hosts. Of the
      schistosomal species, S. mansoni, S haematobium and S. japonicum are the most
      important to man and the most widely distributed. The infection affects about 200
      million individuals in 74 countries of Latin America, Africa and Asia. Far less
      commonly, schistosomes reach the central nervous system (CNS). This may occur at
      any time from the moment the worms have matured and the eggs have been laid. For
      this reason, CNS involvement may be observed with any of the clinical forms of
      schistosomal infection. The presence of eggs in the CNS induces a cell-mediated
      periovular granulomatous reaction. When eggs reach the CNS during the early
      stages of the infection or during evolution of the disease to its chronic forms,
      large necrotic-exudative granulomas are found. In-situ egg deposition following
      the anomalous migration of adult worms appears to be the main, if not the only,
      mechanism by which Schistosoma may reach the CNS in these stages. The mass effect
      produced by the heavy concentration of eggs and the presence of large granulomas
      in circumscribed areas of the brain and spinal cord explains, respectively, 1)
      the signs and symptoms of increased intracranial pressure and focal neurological
      signs; and 2) the signs and symptoms of rapidly progressing transverse myelitis,
      usually affecting the lumbosacral segments of the spinal cord. Most of the cases
      of CNS involvement associated with the hepatosplenic and cardiopulmonary chronic
      forms, or with severe urinary schistosomiasis, though more frequent, are
      asymptomatic. In the patients with these clinical forms, the random and sparse
      distribution of eggs in the CNS indicates that the embolization of eggs from the
      portal mesenteric system to the brain and spinal cord constitutes the main route
      of CNS invasion by Schistosoma. The discrete inflammatory reaction elicited by
      the sparsely distributed eggs in the CNS explains the lack of neurological
      symptoms that could be produced by egg deposition.

PMID- 9034572
TI  - Trichinosis.
AB  - Trichinosis is a worldwide zoonotic disease closely related to cultural and
      dietary habits caused by a nematode Trichinella spp. Human infection is acquired
      through ingestion of undercooked meat containing infective encysted larvae. There
      are two cycles of transmission, one domestic and the other wild. A complete life
      cycle develops in a single host harboring adult worms in the small intestine,
      from which newborn larvae migrate and finally encyst in striated muscle.
      Traumatic and immunological alterations are responsible for the main clinical
      features, including diarrhea, febrile syndrome, myalgias, oculopalpebral signs
      and eosinophilia. Cardiovascular, lung and CNS involvement characterize severe
      trichinosis. CNS inflammatory infiltration and damage may result from larval
      migration and vascular obstruction, or from the effect of toxic parasite
      antigens, or eosinophil infiltration. Humoral and cellular immune host response
      are relevant both to protect against re-infection and for immunodiagnosis. DNA
      probes and PCR technology may help to identify Trichinella spp. Muscle biopsy may
      disclose T spiralis larvae coiled within a muscle fibre host nurse cell
      surrounded by a capsule. Inflammatory infiltration includes monocytes, plasma
      cells, eosinophils and T lymphocytes mainly of the suppressor/cytotoxic
      phenotype. Histological appearance and histochemical profile of the host nurse
      cell differ from that of striated muscle fibre and are partly indicative of
      regeneration. Our own histological and histochemical findings in experimental
      studies of infected mouse muscle support the concept that changes induced by the
      larva encysting within a single host skeletal muscle fibre which becomes a nurse
      cell are unique of Trichinella infection. Interestingly, no dystrophin could be
      detected within the host nurse cell-capsule interface. It has been advanced that
      larva-induced host muscle fibre changes may be regulated at muscle gene
      transcription level whilst host regulatory pathways governed by cell cycle phase
      may also contribute to larval development.

PMID- 9034573
TI  - Echinococcosis.
AB  - Echinococcosis is a human disease caused by the larval form of Taenia
      echinococcus, which lives in the gut of the dog, wild canides and other
      carnivorous animals which represent the definitive hosts and involves as
      intermediate hosts both domestic and wild animals. Humans become accidental
      intermediate hosts by ingesting Taenia eggs. The main species pathogenic for man
      are E granulosus causing cystic echinococcosis with worldwide distribution and
      endemic in sheep and cattle breeding countries, and E multilocularis causing
      alveolar echinococcosis, with preferential distribution in the northern
      hemisphere. After ingestion of contaminated food, hexacanth embryos migrate by
      the portal system to liver and later lung, brain and other tissues. Symptoms are
      related to both cyst location and size. E granulosus infection of the central
      nervous system (CNS) may be primary or secondary and has been estimated to be low
      (2%). Sharply demarcated, spherical and intraparenchymal, cysts may reach a large
      size causing neurological symptoms. Spilling of cyst fluid due to trauma or
      surgery may trigger anaphylaxis as well as disseminated infection. Host reaction
      is minimal in the brain but a foreign giant cell reaction may develop. E
      multilocularis develops within the liver as a rapid invasive pseudomalignant
      growth and may metastasize to the CNS, where estimated incidence reaches 5%.
      Hydatid antigens induce an immune reaction in the host which is helpful for the
      diagnosis. DNA probes and PCR may be applied to differentiate between
      Echinococcus spp. Although the host develops an immunological protection from
      reinfection, the parasite evades host immune attack. A wide range of evasion
      mechanisms have been advanced, including a barrier for host cells due to hydatid
      cyst laminated cuticle, polyclonal activation of lymphocytes by parasite soluble
      antigens, and depression of host cell immune responses. Chronic stimulation of
      the host by cyst fluid antigens leads to increased specific IgG4 production,
      which might act as blocking antibodies against anaphlaxis suggestive of host
      response immunomodulation.

PMID- 9034574
TI  - Neurocysticercosis.
AB  - Cysticercosis is an infection caused by Taenia solium larvae (cysticerci). When
      the cysticercus is lodged in the central nervous system (CNS), the disease is
      known as neurocysticercosis (NCC). NCC is the most frequent and most widely
      disseminated human neuroparasitosis. It is endemic in many parts of the world,
      particularly Latin America, Africa, and Asia, and still relatively frequent in
      Portugal, Spain and Eastern European countries It is also endemic in developed
      countries with high rates of immigration from endemic areas. Man may act as an
      intermediate host after ingestion of mature, viable T. solium eggs via the fecal
      oral route. The development of lesions in the brain and leptomeninges, and the
      consequent of onset of symptoms associated with NCC are mainly due to the host
      immune-inflammatory response. As long as the cysticercus remains viable, there is
      relative host immune tolerance. It is only when the parasite dies that massive
      antigen exposure occurs, with intensification of the immune response/inflammatory
      reaction and the appearance or worsening of symptoms. NCC can be asymptomatic or
      cause widely varied clinical manifestations, such as seizures, increased
      intracranial pressure, ischemic cerebrovascular disease, dementia, and signs of
      compression of the spinal roots/cord. The combination of two or more symptoms is
      common. Such clinical polymorphism is determined by 1) the number of lesions
      (single or multiple cysticerci); 2) the location of CNS lesions (subarachnoid,
      intracerebral, intraventricular, intramedullary); 3) the type of cysticercus
      (Cysticercus cellulosae, Cysticercus racemosus); 4) the stage of development and
      involution of the parasite (vesicular or viable, necrotic, fibrocalcified
      nodule); and 5) the intensity of the host immune-inflammatory response (no
      inflammatory reaction, leptomeningitis, encephalitis, granular ependymitis,
      arteritis).

PMID- 9034575
TI  - Viruses and rickettsiae.
AB  - In this review I shall try to provide a brief, up-to-date, account of the
      neuropathology of those viral and rickettsial diseases that are particularly
      prevalent in tropical regions. These diseases are not, however, exclusive to the
      tropics. Some, such as AIDS, are common in temperate regions as well, though
      others are closer to being exclusively tropical, such as some of the arthropod
      borne (ARBO) virus encephalides. The latter are dependent for their dissemination
      on an existence during part of their infectious cycle in insects which are, in
      turn, climatically and seasonally sensitive. This necessarily limits their
      geographical distribution. Factors that influence some of the other diseases are
      less closely dependent on climate and geography and reflect more the social or
      cultural conditions under which people live. Thus, diseases that depend for their
      spread on forms of human behavior such as promiscuity or drug abuse (AIDS), or
      poor hygiene and living conditions (polio, rickettsial diseases) or on contact
      with domestic and other animals (rabies) may occur in a more widespread
      distribution, for the tropics are not the only places that afford opportunities
      for these diseases to flourish. I shall select for discussion aspects of the
      pathology of these diseases that are currently undergoing investigation but will
      aim to present these against the backdrop of more established aspects of their
      pathology. Recent reviews of the pathology of viral encephalitis can be found in
      Hamilton and Wiley (33) and Esiri and Kennedy (20) and of HIV-1 infection in
      Price & Sidtis (78) and Scaravilli (85).

PMID- 9034576
TI  - Case of the month. July 1996--precocious puberty.
AB  - A 4 year old girl presented with precocious puberty. She had pubic hair, breast
      buds and showed a height and weight well above the 95th percentile. An MRI scan
      of the head revealed a discrete mass in the tuber cinereum which was surgically
      removed. Microscopic examination showed a hypothalamic hamartoma. The clinical,
      radiologic and microscopic findings in this case are "classic" for hypothalamic
      hamartoma Other clinical presentations are discussed. The patient's symptoms have
      regressed following surgery and there has been no regrowth in six months.

PMID- 9034577
TI  - Case of the month. August 1996--frontal lobe tumor in 11 year old girl.
AB  - An 11 year old girl presented with an 8 month history of left temporal headaches
      with new onset of nausea and vomiting with increased severity of headaches. An
      MRI scan showed a frontal lobe mass. The tumor was resected and histologic
      studies demonstrated a central neurocytoma. The clinical, radiologic and
      pathologic aspects (including immunohistochemistry and electron microscopy) of
      central neurocytomas are reviewed and the atypical features of this case
      described.

PMID- 9034578
TI  - Case of the month. September 1996--new onset hemiparesis.
AB  - A 44 year old woman developed left hemiparesis. CT scan showed a contrast
      enhancing lesion in the right periventricular area. A stereotactic biopsy was
      performed. The initial impression was that of an astrocytic neoplasm, however the
      presence of perivascular lymphocytes and numerous foamy macrophages led to
      consultation. Special studies demonstrated demyelination and lymphocytic
      infiltrate with relative axonal preservation consistent with multiple sclerosis.
      Additional history from the patient revealed a flu-like illness one week prior to
      the hemiparesis and a history of transitory visual problems, possibly early
      manifestations of her multiple sclerosis.

PMID- 9034579
TI  - Effect of constant and of changing photoperiods on age at first egg and related
      traits in pullets.
AB  - 1. The effects of constant photoperiods and of single (5 h) changes in
      photoperiod applied at 12 or 17 weeks of age upon age at first egg (AFE) were
      studied using ISA Brown and Shaver 288 pullets. 2. Birds reared from 2 d of age
      until after maturity on constant 10 h photoperiods matured 8 d earlier than birds
      reared on constant 8 h and 5 d earlier than the average for 13 or 18 h
      photoperiods. 3. A single increment in photoperiod from 8 to 13 h advanced AFE by
      23 d (compared to 8 h constant day controls) when applied at 84 d, but by only 6
      d when given at 119 d. An increase in photoperiod from 13 to 18 h advanced AFE by
      only 4 d, averaged across breeds and age at increase. A reduction in photoperiod
      from 13 to 8 h delayed AFE by 22 d when given at 84 d and by 16 d at 119 d. A
      similar 5 h reduction in photoperiod, but from 18 to 13 h, retarded maturity by
      11 d in ISA Brown pullets, but only when given at 84 d, and delayed AFE in Shaver
      288 by 12 d, but only when given at 119 d. This interaction may be partly
      explained by the different physiological stages reached by the two breeds when
      the photoperiod was changed. 4. Under constant daylengths cumulative food intake
      before first egg was positively correlated with photoperiod, but the early AFE
      for birds on 10 h photoperiods resulted in this group having the lowest
      cumulative food intake to first egg. 5. A 5 h increase in photoperiod at 84 d
      significantly reduced the food consumed to first egg, but had no effect when
      given at 119 d. A 5 h decrease in photoperiod generally increased the food
      consumed to first egg, but the effect was only significant when the daylength was
      reduced from 13 to 8 h at 119 d. Food intake to first egg in birds subjected to a
      change in photoperiod was highly correlated with AFE. 6. The data confirm that
      sexual development in growing pullets responds more to changes in photoperiod
      than to the absolute daylength, that changes made at different daylengths are not
      equivalent and that sensitivity changes with age.

PMID- 9034580
TI  - Behavioural adaptation of laying hens to dilution of diets under mash and pellet
      form.
AB  - 1. Two laying diets, control (A) and a low-energy (B) diet diluted by adding 450
      g/kg wheat bran, were fed to semi-heavy hens in three different forms: mash,
      small pellets and large pellets. The behavioural adaptations and the production
      characteristics for these six regimens were studied on 72 individually caged
      hens, between 19 and 29 weeks of age, subjected to a lighting pattern of 14 h
      light/24 h. 2. Diet B, as mash, showed a lower apparent physical density than the
      others. The hardness and durability of the pelleted diets were similar. 3. Hens
      fed the mash diet B could not completely adjust their food intake to compensate
      for the dilution and showed reduced egg output and body weight gain compared to
      the other groups. 4. Video observation of each hen for 14 consecutive hours
      showed that mash-fed hens ate for longer periods than pellet-fed hens during the
      first 11 h (proportion of time spent eating: 41.3% mash B, 32.5% mash A and 20%
      to 25% for all the pelleted diets). These differences were less pronounced during
      the last 3 h of the photoperiod. 5. Trough-oriented stereotypies were noted in 14
      out of 22 mash-fed hens and in 12 out of 47 pellet-fed hens. Dilution of the diet
      did not appear to exacerbate stereotyped behaviours under the conditions of the
      study. 6. This experiment demonstrates that the feeding behaviour of laying hens
      is affected by the physical characteristics of the diet and that this may lower
      their productivity. 7. Low-energy pelleted diets might be used to feed hens
      efficiently in tropical countries where cereal by-products are abundant.

PMID- 9034581
TI  - Effects of fasting and refeeding on structures of the intestinal villi and
      epithelial cells in White Leghorn hens.
AB  - 1. The fine structural alterations of villi and epithelial cells in each part of
      the small intestine were investigated in layer-type hens fasted for 12 h to 20 d
      or refed for one day after each fasting period. 2. Within the first 24-h-fasting,
      villi of the duodenum showed a remarkable reduction in height and those of the
      jejunum revealed a gradual decrease; such a significant reduction of the villus
      height was not obtained in the ileum. After 36-h-fasting, villus height in each
      part gradually decreased with days of fasting. 3. All intestinal villus heights
      increased after only 1-d-refeeding of various kinds of diets following 3-, 10-,
      or 20-d-fasting. The duodenum especially rapidly recovered even after long-term
      fasting of 20 d but the ileum showed very slow recovery, suggesting that the
      ileum seems to be inactive in absorptive function. 4. These variable alterations
      of villus height in the proximal intestine suggest that the higher intestinal
      absorptive ability is under the normal feeding, the more rapidly villus height is
      influenced by nutritional conditions. 5. Cell area and cell mitosis decreased
      after fasting, the latter showing a marked reduction. However, in spite of a
      remarkable decrease of cell mitosis in the proximal intestine after fasting,
      refeeding activated cell renewal and it soon reached control levels,
      demonstrating that the villus height mainly varied with the numbers of epithelial
      cells. 6. In the epithelial cells of the proximal intestine in chickens fasted
      for 20 d, large lysosomal autophagous vacuoles including mitochondria and dense
      bodies were observed. These were reduced in size by refeeding for only one day,
      suggesting that fasting may cause intracellular digestion through lysosomal
      autophagy. 7. These results lead to the conclusion that long-term for force
      moulting is possible, that a high protein and high energy diet can be fed
      immediately after fasting and that a cell undergoing lysosomal autophagy in
      normal chickens indicates undernutrition.

PMID- 9034582
TI  - Effect of tibial dyschondroplasia on carcase part weights and bone
      characteristics.
AB  - 1. The effect in broilers of tibial dyschondroplasia (TD) on carcase part weights
      and bone characteristics was investigated by studying the progeny of 10 sires and
      40 dams. The correlations between TD and bone variables were also estimated. 2.
      The incidence of TD was 59% at 42 d of age. There were no significant differences
      in slaughter weight of birds with and without TD. However, in females, breast
      weight was heavier in affected birds. Neck plus back weight of birds with TD was
      significantly heavier than in birds without TD. 3. Breast blister frequency of
      birds was independent of the presence of TD. 4. Birds with TD had longer bones
      than birds without TD. However, TD had no effect on tibiotarsus weight, width,
      ratio of tibiotarsal to body weight and ash. A negative correlation was observed
      between TD score and bone ash percentage.

PMID- 9034583
TI  - Maturation and ovulation of Japanese quail oocytes under in vitro conditions.
AB  - 1. An in vitro system for ovulation and maturation of Japanese quail oocytes is
      described. 2. Ovarian follicles removed from the ovary at 2, 4 or 6 h before the
      estimated time of ovulation may ovulate under in vitro conditions. 3. The
      presence of progesterone in the medium had a stimulatory effect on the process of
      maturation, as has been shown for Xenopus oocytes.

PMID- 9034584
TI  - Artificial increase of eggshell conductance improves hatchability of early laid
      goose eggs.
AB  - 1. The purpose of this work was to test the possibility of increasing the
      hatchability of goose eggs with low mass specific eggshell gas conductance (Gsp),
      by drilling holes through the eggshell into the air cell, and thus solving both
      the low water loss rate and low oxygen availability problems. 2. A linear
      relationship was found between the area of a hole drilled and the apparent
      increase in eggshell gas conductance (G). Drilling more than one hole increased
      apparent G 3-6 times more than one hole only, of the same total area. 3. Hole
      drilling did not increase egg contamination. The drilling of a 5 mm2 hole on day
      17 of incubation increased hatchability both in laboratory tests and in
      commercial hatcheries (6.1% and 10.5% respectively). 4. Drilling holes on days 15
      to 22 of incubation increased hatchability when the predicted mean water loss was
      lower than 14%. Drilling on day 25 did not have a significant effect, and
      drilling on day 11 of incubation was too early. 5. Drilling a hole into the
      aircell (during the second half of incubation) may increase hatchability of low
      conductance eggs, although oxygen pressure under the eggshell should then be
      checked in order to evaluate oxygen availability to the embryo.

PMID- 9034585
TI  - Repeatability and phenotypic correlations for body weight and reproduction in
      commercial ostrich breeding pairs.
AB  - 1. Reproduction is an important aspect of ostrich farming, where income is mainly
      derived from hides and meat. No estimates of repeatability or phenotypic
      correlations for reproduction and body weight are currently available for
      commercial ostriches. 2. Means, standard deviations, repeatability coefficients
      and phenotypic correlations for and among reproductive traits and body weight
      were computed for the average yearly production of 42 to 67 mixed age ostrich
      breeding pairs maintained on the Klein Karoo Agricultural Development Centre from
      1990 to 1994. The among-breeding-pair variance component was used in the
      repeatability estimations, as the pairing off of the same male:female
      combinations repeatedly resulted in the confounding of these effects. 3.
      Phenotypic correlations of male body weight with egg production performance (
      0.20) and female body weight with hatchability percentage (-0.16) were negative.
      Correlations of egg production performance with infertility (-0.20) and
      hatchability (0.23) percentages were favourable. 4. The repeatability of annual
      adult body weight was 0.68 +/- 0.05 in male ostriches and 0.61 +/- 0.05 in
      females. 5. Ostrich reproduction traits were extremely variable. An appreciable
      portion of this variation could be attributed to the repeatable nature of
      breeding pair performance from year to year. All the reproduction traits analysed
      were moderately repeatable, ranging from 0.38 +/- 0.07 (hatchability percentage)
      to 0.51 +/- 0.06 (percentage of embryonic deaths). Egg production performance
      during the first breeding season of 17 breeding pairs for which data were
      available predicted subsequent performance satisfactorily, suggesting that
      selection decisions can be made at quite an early age.

PMID- 9034586
TI  - Effect of dietary protein content on live and carcase performance of heterozygous
      naked neck and normally feathered broilers.
AB  - 1. An experiment was conducted to determine the effect of different dietary
      protein contents on the performance of naked neck (Na/na) and normally feathered
      (na/na) broilers. 2. Chicks from the two genotypes were reared in wire-floored
      cages and divided at random into 3 groups. Birds were fed on high protein (HP,
      12.99 MJ ME, 238 g crude protein/kg and 12.94 MJ ME, 216 g crude protein/kg from
      0 to 3 and 3 to 7 weeks, respectively), medium protein (MP, 12.99 MJ ME, 219 g
      crude protein/kg and 12.87 MJ ME, 201 g crude protein/kg from 0 to 3 and 3 to 7
      weeks), and low protein (LP, 12.94 MJ ME, 205 g crude protein/kg and 12.75 MJ ME,
      184 g protein/kg from 0 to 3 and 3 to 7 weeks) diets. 3. The LP diets resulted in
      a significantly lower daily body weight gain of males from 0 to 3 weeks. Dietary
      protein content had no effect on body weight gain from 3 to 7 weeks, body weight
      at 7 weeks, and the food intake of birds. Carcase composition of birds from both
      genotypes was unaffected by dietary protein. 4. Naked neck birds had
      significantly higher body weights at 7 weeks. Yields of carcase and breast of
      Na/na males were significantly higher than those of na/na males. There were no
      significant differences between females from the two genotypes as regards carcase
      yield. 5. It was concluded that the dietary protein requirements of naked neck
      birds were similar to those for normally feathered birds.

PMID- 9034587
TI  - Studies on the toxic effects of crambe meal and two of its constituents, 1-cyano
      2-hydroxy-3-butene (CHB) and epi-progoitrin, in broiler chick diets.
AB  - 1. Studies were undertaken to determine a safe inclusion rate for crambe (Crambe
      abyssinica) meal in broiler chick diets, and to determine the mechanism for
      adverse effects by investigating its constituents; 1-cyano-2-hydroxy-3-butene
      (CHB) and 3-butenyl glucosinolate (epi-progoitrin, E-PG). 2. Crambe meals were
      prepared to differ in E-PG (19, 36 and 40 g/kg) and CHB contents (0.1, 0.7 and
      1.9 g/kg), and with either active or inactive thioglucosidase. 3. Meals were fed
      to 7-d-old broiler chicks at 50 or 100 g/kg of the diet for 12 or 13 d. In
      separate studies, isolated E-PG or CHB were mixed into the diet or administered
      by gavage to 7-d-old broiler chicks in amounts equivalent to 50 or 100 g/kg
      crambe meal diets for 10 and 12 d, respectively. 4. Weight gain decreased (P <
      0.05) in chicks fed on the high glucosinolate crambe diets or isolated E-PG. Food
      consumption decreased (P < 0.05) in chicks fed on the diet containing the high E
      PG meal with active enzyme. 5. Mild liver lesions and increased serum aspartate
      aminotransferase were found in chicks fed on the diet containing the high
      glucosinolate meal with active enzyme. Other organs, including thyroids, were
      normal. 6. Commercially-processed crambe meal appeared safe at an inclusion rate
      of 50 or 100 g/kg diet, but could not be recommended at this point for long term
      feeding.

PMID- 9034588
TI  - Routes of yolk utilisation in the newly-hatched chick.
AB  - 1. This study was conducted to study the routes by which yolk is utilised in the
      chick during the initial posthatch phase. 2. Transfer from yolk to blood was
      examined by injecting, in the form of labelled compounds, oleic acid, triolein,
      inulin and dextran into the yolk; movement from yolk to blood was observed up to
      72 h posthatch. 3. Transport of these molecules from blood to yolk was also
      observed by injecting them into the circulation and determining label in yolk.
      The yolk sac membrane was permcable in both directions for all labelled materials
      tested. 4. In the newly-hatched chick, blue dextran injected into the yolk sac
      could be seen moving in pulses into the intestine at irregular intervals.
      Transport of labelled materials from the yolk sac into the intestine was observed
      up to 72 h after hatching, and marker was found in the proximal small intestine
      and gizzard. The yolk stalk provided a pathway for transport to the intestine
      until lymphoid cells began to accumulate, with passage becoming partially
      occluded at 72 h posthatch. 5. Yolk utilisation was more rapid in fed than in
      fasted birds suggesting that the transport of yolk through the intestine could be
      increased by the greater intestinal activity found in fed chicks.

PMID- 9034589
TI  - Effects of anticoagulants and storage (4 degrees C) on packed cell volume (PCV)
      of Nigerian domestic fowl (Gallus domesticus) and guinea fowl (Numida meleagris).
AB  - 1. Studies were conducted to determine the effects of anticoagulants and storage
      (4 degrees C) on the PCV of blood samples from Nigerian domestic fowl (DF) and
      the guinea fowl (GF). 2. Citrate significantly reduced pre-storage PCV of the DF
      in comparison with the effect of ethylenediamine tetra-acetic acid (EDTA). 3. It
      further decreased (P < 0.05) the PCV of the blood of DF and GF over 3 d of
      storage; this was similar to the effect of EDTA on the PCV of the GF blood. 4.
      Citrate and oxalates induced haemolysis of blood of the DF and the GF in storage
      faster than EDTA, but overall the haemolysis was more pronounced from red cells
      of the GF than from those of the DF. 5. The mean fall in the PCV of the DF was
      significant at 3.0 mg EDTA/ml of blood in contrast to the fall in the PCV of the
      GF blood.

PMID- 9034590
TI  - Different characteristics in chick embryos of two broiler lines differing in
      susceptibility to ascites.
AB  - 1. The relationship between the length of incubation, hatching, hypoxic
      condition, thyroid hormones and the occurrence of ascites were studied in embryos
      of 2 broiler lines differing in susceptibility to the ascites syndrome. 2. Both
      the time of external pipping (ep) and hatching of embryos from the ascites
      resistant (AR) broiler line was earlier compared to the ascites-sensitive line
      (AS). The interval between internal pipping (ip) and ep was the same between the
      lines, but the interval between ep and hatching was shorter in the resistant
      line. 3. The T3 and T4 concentrations in plasma of the AS line were lower
      compared to the AR line. 4. Analyses of partial pressures of oxygen (pO2) and
      carbon dioxide (pCO2) in the air cell of the egg revealed that at day 18 the AS
      embryos had lower pO2 and higher pCO2 concentrations compared to the AR embryos.
      5. The delay in hatching of the AS embryos might induce a more pronounced and/or
      extended hypoxic environment, thereby creating an environment that evokes
      ascites.

PMID- 9034591
TI  - Gene therapy for cancer--in the dock, blown off course or full speed ahead?
AB  - Gene therapy no longer seems to generate the unlimited optimism that it once
      inspired. So much so that the field has recently attracted the close scrutinies
      of the Director of the NIH himself. In this introductory chapter, the background
      is presented to the rise, and apparent decline, of the gene therapy of cancer and
      serves as a prelude to this issue of Cancer Metastasis Reviews which is designed
      to ask whether the field is worthy of its highly-priced and highly-hyped market
      profile.

PMID- 9034592
TI  - Antisense approaches to the gene therapy of cancer--'Recnac'.
AB  - This review has looked at the wide-ranging research initiatives in the field of
      antisense technology. It starts with the philosophy behind antisense DNA and the
      production of antisense RNA from genetic constructs and raises the various
      problems which are being addressed. These include uptake into cells, targeting
      the substrate sequence and cells, the stability of the antisense molecules and
      pharmokinetic considerations within animals. The review talks of the positive
      results attained in vitro and in vivo in animal and plant experiments but also
      addresses the problems many workers have faced in the field. It attempts to
      resolve these differences in terms of the need for further understanding of the
      mechanisms by which the positive results have been obtained. The novel use of
      catalytic ribozymes (RNA) in downregulating genes is also discussed in similar
      terms to antisense DNA and RNA. By taking a case study with a human leukaemia the
      review delves into the mysteries of how different results can be resolved by
      improving the design of ribozymes thereby increasing specificity and preventing
      aberrant reactions. It is concluded that despite a lack of understanding of how
      the biological effects have come about in vitro and in vivo the clinical and
      research developments should resolve the issue of antisense potential for
      rational drug development.

PMID- 9034593
TI  - Direct cell killing by suicide genes.
AB  - Cell death can be induced by genetic intervention in a variety of ways. We review
      genetic prodrug activation therapies using both mammalian and non-mammalian
      enzyme systems as well as the expression of toxin genes and apoptotic triggers.
      Targeting of the genetic intervention using both transductional restriction and
      transcriptional control elements is examined in both in vitro and in vivo
      systems, and the present state of clinical trials is reviewed.

PMID- 9034594
TI  - Immunotherapy I: Cyclosine gene transfer strategies.
AB  - The cytokine approach to gene therapy of cancer stems from early studies of
      direct, repeated injection of recombinant cytokines at the tumor site, and
      extension of the bystander effect that enables a few cytokine gene transduced
      cells in a tumor to bring about its total destruction. This effect can be
      extended through the immune system, since cytokine-activated regression of a
      small mass of tumor cells can afford systemic protection. Transduced cells used
      as a vaccine provide a local concentration of both cytokine and tumor antigens.
      Cytokines sustain antigen uptake and presentation by increasing the immunogenic
      potential of the environment through the recruitment of antigen presenting cells
      and leukocytes, and activation of a cascade of events which amplify and tone up
      the efficacy of a vaccine. The promises and difficulties of this approach are
      discussed by considering what is still missing from experimental studies and what
      can best be done as soon as possible in animals and humans to reach compelling
      conclusions.

PMID- 9034595
TI  - Immunotherapy II: Antigens, receptors and costimulation.
AB  - To generate a cytotoxic T-lymphocyte (CTL) response to cancer cells requires
      tumour-specific antigens appropriately processed and displayed by the MHC
      proteins; T-lymphocytes with receptors of appropriate specificity to recognise
      these; and initial antigen presentation to the immune system in an immunogenic
      context. In vitro, autologous tumour-specific CTL have been raised against a
      number of tumours, thus at least some patients have a suitable combination of
      antigen and receptor. Vaccination with antigen, or with DNA or viral vectors
      encoding the antigen, leading to the presentation of identified antigens in an
      immunogenic context, can activate T-cells which provide protection from tumour in
      animal models. An alternative approach uses gene transfer to T-cells, causing
      them to express novel receptors which direct their cytotoxic activity towards the
      tumour. Non-specific immune adjuvants, and expression of novel antigens on tumour
      cells, are briefly discussed. Recent advances in understanding the requirements
      for T-cell activation suggest that failure to efficiently present antigen in an
      immunogenic context may explain the apparent lack of tumour-specific CTL
      activation in vivo. In mice, expression of the costimulatory molecule B7-1 on
      tumour cells, following gene transfer, allows the modified tumour cells to act as
      antigen-presenting cells, inducing protective and therapeutic CTL responses in
      some cases. Clinical trials of some approaches have commenced, with some
      encouraging results which provide a basis for further development of
      immunological gene therapy.

PMID- 9034596
TI  - Immunotherapy III: Combinatorial molecular immunotherapy--a synthesis and
      suggestions.
AB  - Animal models have clearly shown that tumor cells may be amenable to molecular
      manipulation which can result in immune activation and rejection of unmodified
      cells (Chapters 4 and 5). The challenge now is to design clinical trials which
      have a realistic chance of success, (although the definition of 'success' is
      itself an important issue [see Chapter 9]. How should such a strategy be
      formulated? A review of the previous fifteen years since the first (immune) gene
      transfer studies were reported, encompasses a great wealth of data.
      Unfortunately, far from crystallising a set of unifying principles, these diverse
      reports shroud us in a fog of uncertainty as to how best to proceed. However, if
      this technology is to have practical, widespread application in the treatment of
      cancer patients, it is necessary to identify certain critical immunological goals
      which any protocols should achieve. Clear elucidation of these goals, by unifying
      the huge amount of disparate experimental data, must eventually be accomplished.
      In this chapter, we have reviewed the literature covering the era of molecular
      immunotherapy. We propose four general goals around which widely applicable
      clinical protocols, not necessarily dependent upon tumour type or experimental
      bias, might be based and suggest how they may be achieved in the context of gene
      transfer.

PMID- 9034597
TI  - Chemoprotection of normal tissues by transfer of drug resistance genes.
AB  - The effectiveness of many types of antitumour agent is limited by (i) acute dose
      limiting cytotoxicity, principally myelosuppression but also lung, liver and
      gastrointestinal tract toxicity, (ii) the risk of therapy related secondary
      malignancy and (iii) the inherent or acquired drug-resistance of tumour cells. As
      the management of the acute toxic effects improve, the more insidious effects,
      and particularly haematological malignancies, are anticipated to increase.
      Furthermore, attempts to overcome tumour cell resistance to treatment can lead to
      increased collateral damage in normal tissues. One approach to circumventing both
      the acute toxic and chronic carcinogenic effects of chemotherapy would be to use
      gene therapy to achieve high levels of expression of drug resistance proteins in
      otherwise drug-sensitive tissues. To date the products of the multi-drug
      resistance (MDR-1) and the human O6-alkylguanine-DNA-alkyltransferase (ATase)
      gene have been used in preclinical experiments to demonstrate proof of principle,
      and the former of these is now being tested in a clinical situation. Here we
      discuss the potential of drug-resistance gene therapy to provide chemoprotection
      to normal tissues and examine the prospects for a dual approach which combines
      this with pharmacological sensitisation of tumours to chemotherapeutic agents.

PMID- 9034599
TI  - Gene therapy for cancer, the course ahead.
AB  - Previous chapters have shown that there are a large number of therapeutic
      approaches under consideration for the gene therapy of cancer. Many of these have
      progressed into Phase I clinical trials. However, many of the early results are
      perceived to be disappointing in terms of low levels of gene transfer and
      systemic efficacy. In this concluding chapter, possible solutions to this state
      of unease are addressed, so that gene therapy of cancer can resume on its course
      to become a major contributor to clinical oncology in the years ahead.

PMID- 9034600
TI  - Intermediate filaments.

PMID- 9034598
TI  - Vectors for cancer gene therapy.
AB  - Many viral and non-viral vector systems have now been developed for gene therapy
      applications. In this article, the pros and cons of these vector systems are
      discussed in relation to the different cancer gene therapy strategies. The
      protocols used in cancer gene therapy can be broadly divided into six categories
      including gene transfer to explanted cells for use as cell-based cancer vaccines;
      gene transfer to a small number of tumour cells in situ to achieve a vaccine
      effect; gene transfer to vascular endothelial cells (VECs) lining the blood
      vessels of the tumour to interfere with tumour angiogenesis; gene transfer to T
      lymphocytes to enhance their antitumour effector capability; gene transfer to
      haemopoietic stem cells (HSCs) to enhance their resistance to cytotoxic drugs and
      gene transfer to a large number of tumour cells in situ to achieve nonimmune
      tumour reduction with or without bystander effect. Each of the six strategies
      makes unique demands on the vector system and these are discussed with reference
      to currently available vectors. Aspects of vector biology that are in need of
      further development are discussed in some detail. The final section points to the
      potential use of replicating viruses as delivery vehicles for efficient in vivo
      gene transfer to disseminated cancers.

PMID- 9034601
TI  - Intermediate filaments as dynamic structures.

PMID- 9034602
TI  - Implications of intermediate filament protein phosphorylation.
AB  - Intermediate filament (IF) proteins, a large family of tissue specific proteins,
      undergo several posttranslational modifications, with phosphorylation being the
      most studied modification. IF protein phosphorylation is highly dynamic and
      involves the head and/or tail domains of these proteins, which are the domains
      that impart most of the structural heterogeneity and hence presumed tissue
      specific functions. Although the function of IF proteins remains poorly
      understood, several regulatory roles for IF protein phosphorylation have been
      identified or are emerging. Those roles include filament disassembly and
      reorganization, solubility, localization within specific cellular domains,
      association with other cytoplasmic or membrane associated proteins, protection
      against physiologic stress and mediation of tissue-specific functions.
      Understanding the mechanistic and functional aspects of IF protein
      phosphorylation is providing insights not only regarding the function of this
      modification, but also regarding the function of IF proteins.

PMID- 9034604
TI  - Intermediate filament expression in prostate cancer.
AB  - The human prostate is composed of a series of tubular-alveolar glands and their
      ducts surrounded by a fibro-muscular stroma. The parenchymal glands secrete the
      seminal fluid and are anatomically arranged into the central, peripheral, and
      transitional zones. In this chapter the pattern of intermediate filament
      expression by the various epithelial components of the ducts, tubuloalveolar
      glands, and stroma are described. The changes which occur during malignant
      transformation from normal glands to prostatic intraepithelial neoplasia and
      subsequent invasive carcinoma are presented. The usefulness of cytokeratin
      markers in the diagnosis of prostate carcinoma is also discussed.

PMID- 9034606
TI  - Multiple drug resistance and intermediate filaments.
AB  - One major obstacle to the successful treatment of epithelial derived tumors, such
      as breast and prostate carcinoma, is the presence of a multiple drug resistance
      phenotype. The drug resistance which is observed in growing epithelial derived
      cancer cells could either be an intrinsic, selected and/or an acquired
      characteristic. A survey of the survival data from several laboratories suggests
      that epithelial derived tumor cells, which have never been challenged with
      damaging agents, are in some cases 10 to 2,000 times more resistant to various
      chemotherapeutic agents as compared to hematopoietic cell lines. An intrinsic
      characteristic of epithelial cells is their resistance to the lethal effects of
      multiple types of damaging agents. A major feature of epithelial derived tumors
      is the expression of the intermediate filament type proteins known as
      cytokeratin. The simplest cytokeratin combination, cytokeratin 8 and 18, is a
      major cytoplasmic element within the cells of epithelial derived tumors. Earlier
      work showed that cytokeratin could be modified by mitoxantrone, a
      chemotherapeutic agent used in the treatment of breast cancer. Increasing data
      indicates that the intrinsic drug resistance phenotype is due in part to the
      presence of continued expression of the cytokeratin 8 and 18. The cytokeratin
      dependent drug resistance (C-MDR) has been observed in two different cell types
      that were engineered to contain cytokeratin 8 and 18 expression. The cytokeratin
      monomers are known to self assemble into intermediate filament networks as shown
      by numerous basic studies. Experiments using transfected cell lines which are
      unable to assemble networks indicated that C-MDR does not depend upon the
      formation of an intermediate filament network. Selection of cytokeratin network
      defective tumor cells did not increase their sensitivity to chemotherapeutic
      agents. These data are interesting since it suggests that the C-MDR phenotype is
      not dependent upon the structural nature (i.e. network forming ability) of the
      cytokeratin. Our current working hypothesis is that the interaction of the
      damaging agent with cytokeratin may initiate signaling response(s) for cell
      survival.

PMID- 9034605
TI  - Intermediate filaments in the nervous system: implications in cancer.
AB  - In this review, we describe the different intermediate filament (IF) proteins,
      their assembly into IFs, the functions of IFs and their relation to disease with
      a particular emphasis on the intermediate filaments expressed in the nervous
      system. In the mammalian nervous system, seven intermediate filament proteins are
      known to be expressed in neurons or neuroblasts. These include the three
      neurofilament triplet proteins, which are present in both central and peripheral
      neurons; alpha-internexin, which is the first neuronal intermediate filament
      protein expressed in the developing mammalian nervous system and present
      primarily in CNS neurons in the adult nervous system; peripherin, which is most
      abundant in the PNS; vimentin, which is expressed in neuronal progenitor cells
      along with nestin, as well as in a few adult neurons. In contrast to these neuron
      specific IF proteins, the glial fibrillary acidic protein (GFAP) is glial
      specific and expressed in mature astrocytes. Vimentin and nestin are also
      expressed in glial progenitor cells and vimentin is expressed along with GFAP in
      some mature astrocytes. As a whole, the expression of IF proteins is tissue
      specific and developmentally regulated. As a result, IF proteins are good markers
      for determining the cell origin and differentiation status of tumor cells. For
      example, peripherin is expressed in neuroblastomas, GFAP in astrocytomas and
      neurofilaments in tumors of neuronal origin. However, tumor cells may express IF
      patterns which are irrelevant to their cell origin. Therefore, one has to be very
      careful in using IF patterns as sole indicators of cell origin and
      differentiation status of tumors.

PMID- 9034603
TI  - Oncogenic regulation and function of keratins 8 and 18.
AB  - Keratin 8 (K8) and keratin 18 (K18) are the most common and characteristic
      members of the large intermediate filament gene family expressed in 'simple' or
      single layer epithelial tissues of the body. Their persistent expression in tumor
      cells derived from these epithelia has led to the wide spread use of keratin
      monoclonal antibodies as aids in the detection and identification of carcinomas.
      Oncogenes which activate ras signal transduction pathways stimulate expression of
      the K18 gene through transcription factors including members of the AP-1 (jun and
      fos) and ETS families. The persistent expression of K8 and K18 may reflect the
      integrated transcriptional activation of such transcription factors and, in the
      cases of ectopic expression, an escape from the suppressive epigenetic mechanisms
      of DNA methylation and chromatin condensation. Comparison of the mechanisms of
      transcriptional control of K18 expression with expression patterns documented in
      both normal and pathological conditions leads to the proposal that persistent K8
      and K18 expression is a reflection of the action of multiple different oncogenes
      converging on the nucleus through a limited number of transcription factors to
      then influence the expression of a large number of genes including these
      keratins. Furthermore, correlation of various tumor cell characteristics
      including invasive behavior and drug sensitivity with K8 and K18 expression has
      stimulated consideration of the possible functions of these proteins in both
      normal development and in tumorigenesis. Recent developments in the analysis of
      the functions of these intermediate filament proteins provide new insights into
      diverse functions influenced by K8 and K18.

PMID- 9034608
TI  - Optimization of use of UEA-1 magnetic beads for endothelial cell isolation.
AB  - Most endothelial cells (EC) in the body belong to the microvasculature. Isolation
      and subsequent culture of these microvessel EC contributes greatly to our
      understanding of the heterogeneity and vascular specificity that exist between
      one organ site and another. However, a major obstacle is the overgrowth of
      contaminating cells (fibroblasts, pericytes, smooth-muscle cells) in cultures.
      Since 1990 the use of magnetic beads in combination with either a lectin, Ulex
      europaeus agglutinin-1 (UEA-1), or a monoclonal antibody has represented a
      powerful tool for the isolation/purification of microvessel EC. In the former
      case, operative conditions remain to be optimized to obtain pure cultures of EC.
      We have performed studies to optimize conditions of use for magnetic beads coated
      with UEA-1. Incubating beads with cells, the influences are studied of time,
      temperature, cell concentration, and number of beads per target cell for two cell
      types, human umbilical vein EC (HUVEC) and skin fibroblasts (HSF), either
      isolated or mixed. The effect of the last parameter was also checked on the
      behavior of cells undergoing proliferation after isolation. Results, expressed as
      isolation efficiency (from 40% to 90%) allowed us to select a 15-min incubation
      time at 4 degrees C with rotary agitation, an optimal concentration of 4 x 10(5)
      cells/ml, and an optimal cell:bead ratio of 1:3. From a mixed cell population and
      in these conditions, even very low HUVEC:HSF proportions of 2.5:97.5 allowed us
      to obtain a pure HUVEC population in subsequent culture.

PMID- 9034607
TI  - Role of intermediate filaments in migration, invasion and metastasis.
AB  - The expression of intermediate filament proteins is remarkably tissue-specific
      which suggests that the intermediate filament (IF) type(s) present in cells is
      somehow related to their biological function. However, in some cancers
      particularly malignant melanoma and breast carcinoma, there is a strong
      indication that vimentin and keratin IFs are coexpressed, thus presenting as a
      dedifferentiated or interconverted (between epithelial and mesenchymal)
      phenotype. In this review, two in vitro models are presented which recapitulate
      the interconverted phenotype in human melanoma and breast carcinoma, and allow,
      for the first time, unique observations to be made with respect to the role of
      IFs in cancer progression. These studies have provided direct evidence linking
      overexpression of keratin IFs in human melanoma with increased migratory and
      invasive activity in vitro, which can be down-regulated by substituting dominant
      negative keratin mutants. Overexpression of vimentin IFs in the breast carcinoma
      model leads to augmentation of motility and invasiveness in vitro, which can be
      transiently down-regulated by treatment with antisense oligonucleotides to
      vimentin. Additional experimental evidence suggests that the mechanism(s)
      responsible for the differential expression of metastatic properties associated
      with the interconverted phenotype rest(s) in the unique interaction, either
      direct or indirect, of IFs with specific integrins interacting with the
      extracellular matrix. In this review, we discuss the observations derived from
      the human melanoma and breast carcinoma models to address the hypothesis that the
      ability to coexpress vimentin and keratins confers a selective advantage to tumor
      cells in their interpretation of and response to signaling cues from the
      extracellular matrix. The ramifications of these observations are discussed with
      respect to the patholophysiology of the respective in situ tumors.

PMID- 9034610
TI  - Ability of various inserts to promote endothelium cell culture for the
      establishment of coculture models.
AB  - To select an insert suitable for human umbilical vein endothelial cell (HUVEC)
      culture, we compared several available inserts of 0.2 to 0.45 micron porosity:
      Cellagen (ICN), Transwell-COL (Costar), Millicell-HA and CM (Millipore), Anopore
      (Nunc), Cyclopore (Falcon) in comparison with a control surface (Thermanox). The
      requirements were: (i) to promote attachment, adhesion and proliferation of HUVEC
      (judged by [3H]thymidine incorporation into DNA at days 1, 3, 7); (ii) to allow
      HUVEC visualization by inverted, fluorescence microscopy for uptake of DiI-Ac-LDL
      and scanning electron microscopy, performed at day 9 after seeding. Because
      Transwell and Cellagen are collagen precoated and CM has to be coated for cell
      culture, we performed collagen coating (types I + III or IV) for non-pretreated
      inserts for the purpose of comparison. Our preferences comprise Transwell-COL,
      Cyclopore not coated or coated (whatever the collagen type), and Cellagen.
      However, on a quality/price ratio criterion, Cyclopore, even uncoated, is the
      insert of choice. The HA, CM and Anopore inserts, even coated, do not allow HUVEC
      growth but do not alter positive uptake of acetylated LDL.

PMID- 9034609
TI  - Endothelial cells in culture: an experimental model for the study of vascular
      dysfunctions.
AB  - Culture of endothelial cells started two decades ago and is now a useful tool in
      understanding endothelial physiology and the study of the interaction of
      endothelial cells with blood cells and various mediators. In vitro proliferation
      can be measured by [3H]thymidine incorporation in defined conditions and gives
      reproducible results. Endothelial cells can be activated by several stimuli,
      including cytokines such as tumor necrosis factor-alpha and interleukin-1. Part
      of endothelial cell activation is defined by expression or overexpression of
      leukocyte adhesion molecules. Intracellular adhesion molecule (ICAM), E-selection
      and vascular adhesion molecule (VCAM) are receptor molecules for leukocyte
      adhesion. Leukocyte adhesion to endothelium can be measured in static but also in
      rheologically defined flow conditions. Normal red blood cells (RBCs) do not
      adhere to endothelium, while RBC from patients with sickle cell anemia, diabetes
      mellitus, and malaria have an increased adhesion to endothelium which is mediated
      by specific VCAM, receptor for advanced glycated end-products (RAGE), and ICAM,
      respectively. Binding of blood cells or activation by cytokine is followed by a
      series of reactions in endothelial cells associated with the modulation of
      prostacyclin, nitric oxide, tissue factor, and cytokine production. Modification
      of endothelial cell functions in culture is correlated to in vivo alteration of
      vascular wall properties, further supporting these cells in culture as a relevant
      experimental model.

PMID- 9034612
TI  - Use of human vessels and human vascular smooth muscle cells in pharmacology.
AB  - Relatively limited information is available regarding the mechanisms controlling
      vasomotricity in human vessels. Isolated vessels obtained from patients
      undergoing surgery were used to characterize the role of endothelial factors and
      to study coupling mechanisms between receptors, intracellular calcium, and
      contraction. However, these investigations are limited by the availability of
      tissues and many uncontrolled factors. Cultured human vascular cells were also
      used, but these cells rapidly lose at least some of their differentiated
      characters. Recently, a human blood vessel equivalent was constructed in vitro
      from cultured cells, using tissue engineering. This technique allowed us to
      obtain vessel equivalents containing intima, media, and adventitia layers or
      tubular media layer only. Contraction and rises in intracellular calcium produced
      by agonists were studied, indicating that such human vessel equivalents may
      provide valuable models for pharmacological studies.

PMID- 9034611
TI  - An hypothesis for the interpretation of the contractile response of vascular
      smooth muscle at the cellular level.
AB  - The long preservation and recovery of functional (contractile) properties in
      cultured aortic smooth muscle cells, even after replating or deep-frozen storage
      and the measurement of their responses are now technically settled issues. We
      could thus study extensively the responses of single cultured cells from rat
      thoracic aorta. Responses were elicited by the addition of KCl 40 mmol/L without
      or with a calcium blocker PN 200-100 (10(-6) mol/L); angiotensin II (10(-11)-10(
      6) mol/L) without or with antagonist (losartan 10(-5) mol/L); or serotonin (10(
      9)-10(-4) mol/L) without or with antagonist (naftidrofuryl 10(-5) mol/L). Results
      thus obtained enabled us to propose a new hypothesis for the interpretation of
      the contractile responses of an elastic vascular smooth muscle. The different
      maximal effects of different agonists result mainly from the different
      proportions of cells they can mobilize; the agonist concentration-contraction
      relationship is mainly due to the increase of the proportion of cells involved up
      to a maximal value typical of the agonist used. An antagonist primarily reduce
      the proportion of cells an agonist can mobilize. Some of the consequences of this
      hypothesis are briefly outlined.

PMID- 9034613
TI  - Components of flow-induced dilation in rat perfused coronary artery.
AB  - This study was undertaken to determine the endothelial factors involved in the
      flow-induced dilation of a rat perfused coronary artery. Segments of the right
      interventricular coronary artery were taken from 10-15-week-old male Wistar rats.
      Vessels were mounted in an arteriograph where internal diameter was continuously
      monitored while intraluminal pressure was controlled. Vessels were preconstricted
      with serotonin (10 mumol/L), and the dilation induced by flow (0-800
      microliters/min) was quantified. This dilator effect was measured in control
      conditions, after incubation with L-NAME (100 mumol/L), with indomethacin (100
      mumol/L), and after mechanical destruction of the endothelium (-E). Dilations
      were expressed as percentage of the serotonin-induced constriction, and wall
      shear stress tau due to the physical forces exerted on the wall of the vessel was
      calculated and expressed in dyn/cm2. In control conditions, raising the flow up
      to 800 microliters/min led to an increase in dilation (maximal dilation 63% +/-
      4%) and in shear stress (maximal shear stress 76 +/- 4 dyn/cm2). With
      indomethacin, maximal dilation was 69% +/- 4% and maximal shear stress was 81 +/-
      6 dyn/cm2. With L-NAME or after destruction of endothelium, dilation was greatly
      reduced (39% +/- 3% and 40% +/- 2%, respectively) whereas shear stress values
      were greatly increased (173 +/- 14 and 150 +/- 13 dyn/cm2, respectively). These
      results confirm the viability of this model for the study of flow-dependent
      dilation. This dilation seems to be greatly dependent on NO release. In contrast,
      results do not favor a significant involvement of prostanoid vasodilating
      substance. Without endothelium, a dilation was still observed and showed the
      persistence of an endothelium-independent component of flow-induced dilation in
      this preparation that remains to be determined.

PMID- 9034614
TI  - The human bronchus model in vitro. Pharmacological approach of various components
      involved in the functional response.
AB  - Studying the human bronchi in vitro, and therefore sheltered from the toxicity
      problems inherent in human experiments, makes it possible to conduct a
      monofactorial analysis, disregarding the perturbations engendered by reflex
      phenomena, hemodynamic changes, etc. Analysing the effects of mediators on
      tissues may be less simple that it looks, due to the multiplicity of the cell
      types that are present. For example, in studying the effects of bradykinin we
      have shown that bradykinin is a potent contractile agent of small-diameter
      isolated bronchi, whereas it has no significant contractile effect on larger
      bronchi. The bradykinin-induced contraction results from a contractile component
      due to stimulation of the TP receptor, and of a relaxant component due to
      relaxant prostanoids. The two components of the bradykinin effects are produced
      by stimulation of B2 receptors. In vitro stimulation of bronchi by LPS or
      interleukin-1 beta permits us to obtain hyperreactivity to bradykinin due to
      induction of thromboxane synthetase or isomerase rather than to induction of B2
      receptors or cyclooxygenase. Involvement of the nervous system may persist in the
      in vitro bronchial model, and indeed we have shown, for example, that
      pentamidine, well known for its tussigenic effect, is an indirect
      parasympathomimetic compound. Thus, study of the isolated bronchus permits an
      approach to the mechanisms of action of medicinal drugs. Despite the
      simplification provided compared to the in vivo study, analysis of
      bronchoreactivity on the isolated bronchus must take into account numerous
      parameters which interfere with the proper effects of the substances.

PMID- 9034615
TI  - Antigen stimulation of human pulmonary smooth muscle: an in vitro model of
      inflammation.
AB  - Human airways in vitro contract when stimulated by anti-IgE, whereas human
      pulmonary vessels relax. Leukotriene D4 (LTD4) induced a contractile response in
      the airways, while in pulmonary vessels both contractions and relaxations were
      observed. The LTD4 contractions in airways were blocked by cysLT1 receptor
      antagonists (MK 571, ICI 198615, and BAY x7195). In contrast none of the
      compounds affected the LTD4 contractions of pulmonary veins. These results
      suggest that the leukotrienes which are released during antigen challenge of
      airways and pulmonary vessels may be acting at distinct receptors in the human
      lung.

PMID- 9034616
TI  - Human bronchial smooth muscle responsiveness after in vitro exposure to oxidizing
      pollutants.
AB  - The aims of this work were (1) to determine the dose-response relationship
      between ex vivo exposure to oxidizing pollutants such as nitrogen dioxide (NO2),
      the aldehyde acrolein, and ozone (O3), and the reactivity to agonists in isolated
      human bronchial smooth muscle; and (2) to investigate the alterations in the
      cellular mechanisms of human airway smooth muscle contraction induced by such
      exposures. Experiments were performed in isolated human bronchi obtained at
      thoracotomy. Isometric contraction in response to a variety of agonists was
      compared between pollutant-exposed preparations and paired controls. Short
      exposures to NO2, acrolein, or O3 altered the subsequent airway smooth muscle
      responsiveness in a dose-dependent manner. The cellular mechanisms producing the
      airway hyperresponsiveness observed in vitro are shared by the three pollutants
      and include alterations in airway smooth muscle excitation-contraction coupling
      as well as indirect effects on neutral endopeptidase activity.

PMID- 9034617
TI  - In vitro assessment of environmental toxicology using alveolar cells as target.
AB  - Biphasic culture of alveolar cells (alveolar macrophages and type II cells) has
      been widely developed and permits a precise evaluation of the toxic effects of
      air pollutants. Clearly, in vitro exposure of alveolar cells to high
      concentrations of oxidant gases is responsible for a loss of cell viability. In
      contrast, when exposed to realistic concentrations of gases (NO2, O3), cell
      viability is not altered and various proinflammatory mediators are released. This
      in vitro model has proved to be sensitive at levels of gas exposure of ambient
      air quality standards and appears a sensitive biological indicator of air
      pollutant cell toxicity.

PMID- 9034618
TI  - Biology of glomerular cells in culture.
AB  - The glomerulus is a complex structure including four cell types, namely
      mesangial, visceral epithelial, parietal epithelial and endothelial cells.
      Mesangial cells resemble smooth muscle cells and play a major role in the
      synthesis of the components of the glomerular basement membrane and in the
      vasoreactivity of the glomerular tuft. In particular, they express receptors for
      angiotensin II which mediate mesangial cell contraction, this effect resulting in
      the decrease of the filtration area. They are also the site of synthesis of a
      variety of inflammatory agents which are involved in the development of
      glomerular injury in glomerulonephritis. Visceral epithelial cells, also referred
      to a podocytes, also participate in the synthesis of the normal constituents of
      the glomerular basement membrane. They express receptors for atrial natriuretic
      factor and possess on their surface a number of ectoenzymes. They also, in
      concert with mesangial cells, release metalloproteases which contribute to the
      degradation of the extracellular matrix. Parietal epithelial cells have been
      little studied. They represent the main constituent of the crescents observed in
      extracapillary proliferative glomerulonephritis. Endothelial cells secrete
      vasodilatory agents such as nitric oxide and prostacyclin and vasoconstrictor
      agents such as endothelin which act on the adjacent mesangial cells. New methods
      of culture of glomerular cells are in progress. Their aim is to keep as long as
      possible the physiological phenotype of these cells. Another progress is the
      availability of stable transformed cell lines which represent an abundant source
      of material for biochemical studies.

PMID- 9034619
TI  - Isolated glomeruli and cultured mesangial cells as in vitro models to study
      immunosuppressive agents.
AB  - Immunosuppressive agents, such as cyclosporin A (CsA), by their vasoconstrictive
      properties, induce in vivo in patients and rodents a dramatic fall in renal
      hemodynamics. The aim of this study is to review the ability of some
      physiological and/or pharmacological agents which are supposed to be involved in
      the renal physiopathology of CsA to prevent the contraction induced by CsA in two
      in vitro glomerular models. Isolated glomeruli are obtained by a sieving method
      from male Sprague-Dawley rat superficial cortex. Mesangial cells from these
      isolated glomeruli are cultured in RPM1 1640 medium with 20% FCS in 5% CO2
      atmosphere. The area of isolated glomeruli and cultured mesangial cells is
      assessed by an image analyzer with a video camera. Each glomerulus and cell is
      its own control and is photographed before incubation with any drug (T0) and then
      during incubation at 5, 10, 20, and 30 min. Incubations are performed during 30
      min with 10(-6) mol/L CsA either with a 10 min pretreatment with the vasoactive
      agent or without pretreatment. CsA alone induces a time- and dose-dependent
      decrease in glomerular structure area (-4.7% at 10 min, -10.3% at 20 min, and 
      12.0% at 30 min for isolated glomeruli); Cremophore excipient or control solute
      does not induce any significant decrease in surface area. CsA with 10(-6) mol/L
      verapamil pretreatment induces only a slight decrease: -1.5% at 10 min, -3.0% at
      20 min, and -4.8% at 30 min. Calcium blockers nifedipine and felodipine produce
      similar results. Likewise, with 10(-8) mol/L prostacyclin analog (iloprost), only
      a slight area decrease in mesangial cells is noted: -1.3% at 5 min, -1.8% at 10
      min, and -3.3% at 20 min; with 10(-6) mol/L TXA2 synthesis inhibitor (CGS 12970)
      the results are -2.0% at 10 min, -3.6% at 20 min, and -4.3% at 30 min. Finally, a
      similar protective effect can be noted with 10(-5) mol/L theophylline: -0.4; -1.5
      and -1.9% at 10, 20, and 30 min. In conclusion, CsA-induced contraction in two in
      vitro glomerular models can be partially or even totally prevented by
      pretreatment with various pharmacological agents.

PMID- 9034620
TI  - Interest and limits of in vitro studies in renal vascular endocrinology.
AB  - Various in vitro preparations have been utilized to study the cellular activity
      of vasoactive agents on renal cortical microvessels and on mesangial cells. The
      receptors and the transduction pathways of bradykinin and atrial natriuretic
      factor were characterized on cultured cortical vascular smooth muscle cells from
      the rabbit kidney. A preparation of afferent arterioles that had been freshly
      isolated from the rat kidney was used to study the NO-dependent regulation of
      renin release. The influence of endothelin and angiotensin II on mesangial cell
      proliferation was evaluated, using cocultures of human endothelial and mesangial
      cells. These appropriate in vitro preparations have provided new insights on
      renal vascular endocrinology. However, extrapolation of in vitro data to in vivo
      physiology must be cautious because the phenotype of vascular cells often changes
      in culture conditions.

PMID- 9034621
TI  - Comparative impact of cephaloridine on glutathione and related enzymes in LLC
      PK1, LLC-RK1, and primary cultures of rat and rabbit proximal tubule cells.
AB  - Among kidney tubular epithelial cell types, proximal tubule cells are one of the
      major renal targets for xenobiotics. Several in vitro culture models have been
      proposed for use of proximal tubule cells for in vitro pharmacotoxicology
      studies. This paper reports a comparative study of the response to cephaloridine
      exposure of two established cell lines from pig (LLC-PK1) and rabbit (LLC-RK1)
      kidneys and primary cultures of rat and rabbit proximal tubule cells. These
      cultured cells were first compared for their levels of activity of alpha
      methylglucopyranoside transport, alkaline phosphatase, succinate dehydrogenase,
      and NADPH cytochrome c reductase, their glutathione-dependent activity levels,
      and their adenylate cyclase response pattern to stimulation by PTH and AVP. The
      results presented show major phenotypic differences between these four cellular
      models. The differences observed in glutathione-dependent mechanism activities
      and regulation may in part be responsible for the variability of the responses of
      these four cellular models when exposed to cephaloridine.

PMID- 9034622
TI  - Advantages and limitations of the use of isolated kidney tubules in
      pharmacotoxicology.
AB  - Among the cellular models used in in vitro renal pharmacotoxicology, isolated
      kidney tubules, used as suspensions mainly of proximal tubules, offer important
      advantages. They can be prepared in large amounts under nonsterile conditions
      within 1-2 h; thus, it is possible to employ a great number of experimental
      conditions simultaneously and to obtain rapidly many experimental results. Kidney
      tubules can be prepared from the kidney of many animal species and also from the
      human kidney; given the very limited availability of healthy human renal tissue,
      it is therefore possible to choose the most appropriate species for the study of
      a particular problem encountered in man. Kidney tubules can be used for screening
      and prevention of nephrotoxic effects and to identify their mechanisms as well as
      to study the renal metabolism of xenobiotics. When compared with cultured renal
      cell, a major advantage of kidney tubules is that they remain differentiated. The
      main limitations of the use of kidney tubules in pharmacotoxicology are (1) the
      necessity to prepare them as soon as the renal tissue sample is obtained; (2)
      their limited viability, which is restricted to 2-3 h; (3) the inability to
      expose them chronically to a potential nephrotoxic drug; (4) the inability to
      study transepithelial transport; and (5) the uncertainty in the extrapolation to
      man of the results obtained using animal kidney tubules. These advantages and
      limitations of the use of human and animal kidney tubules in pharmacotoxicology
      are illustrated mainly by the results of experiments performed with valproate, an
      antiepileptic and moderately hyperammonemic agent. The fact that kidney tubules,
      unlike cultured renal cells, retain key metabolic properties is also shown to be
      of the utmost importance in detecting certain nephrotoxic effects.

PMID- 9034623
TI  - Precision-cut dog renal cortical slices in dynamic organ culture for the study of
      cisplatin nephrotoxicity.
AB  - The dog is the non-rodent species the most often used in preclinical drug safety
      evaluation. In this study, we established a new system of precision-cut dog renal
      cortical slices, evaluated their biochemical, functional, and morphological
      integrity, and determined the effects of cisplatin (cis-diamminedichloroplatinum
      (II), CDDP), a very potent nephrotoxic antineoplastic agent used to treat a
      variety of solid tumors, on the viability and histopathology of slices. Precision
      cut renal cortical slices were made perpendicular to the cortical-papillary axis.
      Slices were incubated in DMEM/Ham's F12 culture medium containing 1 g/L glucose,
      2 mmol/L glutamine, and 2 mmol/L heptanoic acid at 37 degrees C in an atmosphere
      of 5% CO2-70% O2-25% N2 in dynamic organ culture. Our results showed that slices
      maintained ATP and GSH content, protein synthesis, Na(+)-dependent uptake of
      glucose inhibited by phlorizin, PAH (p-aminohippuric acid) uptake inhibited by
      probenecid, and TEA (tetraethylammonium) uptake inhibited by mepiperphenidol for
      at least 6 h of culture, and morphological integrity up to 24 h. After 6 h of
      exposure, CDDP induced vacuolation and cell necrosis in the epithelial tubular
      cells of slices with a concentration-related increase in extension but not in
      severity. The development of the lesions started in the proximal tubules and
      extended to the distal tubules. The location and the extension of the lesions
      confirmed the observations in dog kidneys after in vivo treatment with CDDP by
      the intravenous route. The concentration-related decrease in slice viability
      after 6 h exposure to CDDP was in keeping with the extension of the
      histopathological lesions in the renal parenchyma. The slice viability was
      unaffected up to 0.63 mmol/L CDDP. At 1.25 and 2.5 mmol/L CDDP, slice viability
      fell by 35% and 75%, respectively. These results suggest that precision-cut dog
      renal cortical slices in culture may be suitable for addressing the specific
      nephrotoxicity issues encountered in this species.

PMID- 9034624
TI  - Stimulated secretion of lysosomal enzymes induced by drugs in transimmortalized
      proximal tubule mouse kidney cells.
AB  - We summarize the results of study of the properties of two models of
      transimmortalized proximal tubule epithelial cells derived from the kidneys of
      transgenic mice harboring the SV40 large T and little t antigens/L-pyruvate
      kinase hybrid gene. The two cell lines, referred to as PKSV-PCT and PKSV-PR
      cells, maintained for long-term passages the main biochemical and functional
      properties from the convoluted and terminal parts of the proximal tubule,
      respectively, from which they were derived. In PKSV-PCT cells, gentamicin induced
      lysosomal alkalinization, decreased the cellular N-acetyl-beta-D-glucuronidase,
      and stimulated its secretion in a dose-dependent manner. The results indicate
      that these models of mouse proximal cultured cells could be suitable models for
      the study of the cellular action of drugs.

PMID- 9034626
TI  - New orientations of in vitro models: why? How?
AB  - From the beginning of cell cultures, the aim of all researchers has been to
      perform culture of a pure population of a particular cell type. However, the
      monolayer culture (of one type of cell) rapidly showed its limits concerning
      growth capacity and especially maintenance of the differentiated functions. These
      findings led to the design of increasingly complex in vitro models. Among them we
      can distinguish culture onto cellular matrices and into cellular matrices, or
      tridimensional cell culture. Cocultures in two-compartment dishes or one
      compartment dishes, heteroculture, and tissue slices in vitro are other
      approaches deserving mention. Several examples were reported. Finally,
      immortalized and transfected cell lines exhibit a different state of complexity.

PMID- 9034625
TI  - Rat metanephric organ culture in terato-embryology.
AB  - The development of the permanent mammalian kidney, or metanephros, depends on
      mesenchymal-epithelial interactions, leading to branching morphogenesis of the
      ureteric bud that forms the collecting ducts and to conversion of the metanephric
      mesenchyme into epithelium that forms the nephrons. Rat metanephric organ culture
      in which these interactions are maintained is a valuable in vitro model system
      for investigating normal and abnormal renal organogenesis. Methods were designed
      to evaluate either the capacity of the ureteric bud to branch or that of the
      mesenchyme to form nephrons. Both are based on specific staining of the ureteric
      bud and the glomeruli with lectins. Using this approach, we have shown that
      retinoids are potent stimulating factors of nephrogenesis, acting through an
      increase in the branching capacity of the ureteric bud. On the other hand,
      several drugs such as gentamicin and cyclosporin A were found to reduce the
      number of nephrons formed in vitro. While gentamicin affects the early branching
      pattern of the ureteric bud, cyclosporin may affect the capacity of the
      mesenchyme to convert into epithelium. This methodology therefore appears a
      potentially useful tool for toxicological studies of new drugs.

PMID- 9034627
TI  - Cell-specific mechanisms of estrogen receptor in the pituitary gland.
AB  - Analysis of the mechanism of action of estrogen receptor shows protein and mRNA
      polymorphism within distinct pituitary receptor-positive cells. The lactotropes
      exhibit unique properties in these mechanisms that distinguish them from
      gonadotropes. Therefore, this cell type constitutes an especially interesting
      model in the male as well as in the female for estrogen receptor studies.

PMID- 9034628
TI  - Cell-based therapy of acute liver failure: the extracorporeal bioartificial
      liver.
AB  - The need for an alternative treatment to orthotopic liver transplantation for
      acute liver failure is a major issue, and systems capable of temporarily
      providing liver functions are being actively tested. Liver assist devices based
      on detoxication by dialysis or hemoperfusion through various membranes or
      cartridges proved to be inefficient because of their lack of metabolic function.
      An extracorporeal hybrid bioartificial liver might be an appropriate treatment,
      since it can provide liver-specific functions, maintain the patient alive, and
      allow spontaneous recovery of the patient's own liver or act as a bridge toward
      liver transplantation. Many devices have been proposed, including flat culture
      substrates, hollow-fiber bioreactors, or microcarriers, using xenogenic
      hepatocytes or hepatoma cell lines. Various drawbacks of these devices led us to
      attempt to develop a reliable extracorporeal bioartificial liver based on
      alginate bead-entrapped hepatocytes. This system was used successfully for the
      correction of the Gunn rat genetic defect, which results in lack of bilirubin
      conjugation. The development of this system for clinical purposes requires large
      yields of functional hepatocytes. We have isolated normal porcine hepatocytes by
      collagenase perfusion of the liver. Cells were immobilized in membrane-coated
      alginate gel beads, which were subsequently inoculated into a bioreactor. Porcine
      hepatocytes expressed liver-specific functions at high levels, particularly
      protein neosynthesis and enzymatic activities involved in detoxication and
      biotransformation processes. In addition, hepatocytes entrapped in coated
      alginate beads were isolated from immunoglobulins. This system represents a
      promising tool for the design of an extracorporeal bioartificial liver in human
      beings.

PMID- 9034629
TI  - Vascular endothelial cells: targets for studying the activity of hair follicle
      cell-produced VEGF.
AB  - Fetal bovine aortic endothelial cells (FBAEC) were exposed to purified fractions
      of conditioned medium from cultures of hair dermal papilla cells (DPC) to
      determine the existence of any vascular endothelial growth factor (VEGF)-like
      paracrine activity of the latter. Such fractions were tested for stimulation of
      growth and migration of cultured FBAEC. In addition, VEGF secretion by DPC was
      measured by radioassay of VEGF receptors using FBAEC as target cells. The results
      showed that stimulation of FBAEC proliferation and migration following exposure
      to purified conditioned medium was dose-dependent. Radioreceptor assays of
      recombinant VEGF and purified DPC-conditioned medium showed competitive VEGF
      binding in FBAEC.

PMID- 9034630
TI  - Nitric oxide (NO) donor 3-morpholinosydnonimine antagonizes cyclosporin A-induced
      contraction in two in vitro glomerular models.
AB  - Cyclosporin A induces in vivo a severe nephrotoxicity characterized by a large
      decrease in renal hemodynamics. The aim of this study is to establish the ability
      of the known NO donor 3-morpholinosydnonimine (SIN-1) to prevent the cyclosporin
      A-induced contraction by using rat isolated glomeruli and cultured glomerular
      mesangial cells. Isolated rat glomeruli are obtained from the renal superficial
      cortex by a sieving method. Mesangial cells are cultured in RPMI 1640 with 15%
      fetal calf serum. The planar surface area (PSA) of either isolated glomeruli or
      mesangial cells is assessed using an image analyzer. Each glomerulus or mesangial
      cell serves as its own control through calculation of the area before any drug
      incubation and after incubation for 10, 20 and 30 min either in control solution
      or in control solution with cyclosporin A alone or cyclosporin A and SIN-1.
      Cyclosporin A (10(-6) mol/L) induces an important time-dependent contraction of
      either glomerulus or mesangial cell. When pretreated with different
      concentrations of SIN-1 (10(-4) to 10(-9) mol/L), only a slight size decrease is
      noted. In conclusion, a direct constrictive effect of cyclosporin A in isolated
      glomeruli and mesangial cells can be prevented by the NO donor SIN-1, suggesting
      an important involvement of the nitric oxide pathway in the cyclosporin A-induced
      nephrotoxicity.

PMID- 9034631
TI  - Description of an in vitro angiogenesis model designed to test antiangiogenic
      molecules.
AB  - Angiogenesis is involved in numerous pathologies. Studies with in vitro models
      allow the description and analysis of the different steps involved in this
      process under defined culture conditions. We describe a controllable and
      reproducible in vitro model. We assessed the usefulness of this model with two
      different cell lines: human umbilical vein endothelial cells and bovine retinal
      endothelial cells. These cells reorganize themselves and change their phenotypes
      within 24 h after seeding under our culture conditions (low human serum
      percentage, defined cell density, fibrin matrix) to form 'capillary-like
      structures' (CLS) in vitro. We showed that, depending on the cell line used, the
      fibrinolytic activity of the cells was a determining factor which could induce or
      prevent the formation of the CLS. Inhibitors of angiogenesis can be tested using
      such a model.

PMID- 9034632
TI  - An in vitro nucleoside analog screening method for cancer gene therapy.
AB  - Suicide genes that sensitize cells to drugs that are normally nontoxic at
      therapeutic levels represent an important approach in human gene therapy
      research. We have developed an in vitro screening assay to assess the modulation
      of nucleoside analogs after transfection of a vector expressing the herpes
      simplex virus thymidine kinase gene (HSV-TK). The thymidine kinase gene enhances
      nucleoside phosphorylation to nucleotides that kill cells by blocking DNA
      elongation. Cells lines used are 3T3-NIH fibroblasts (parental cells) and 3T3
      TKc3 (HSV-TK gene-transfected 3T3-NIH). Two types of analysis are performed: a
      cytotoxicity assay, the neutral red uptake assay to assess the IC50 on the two
      cell lines, and an HPLC analysis coupled to a radiochemical flow detector to
      evaluate metabolic profiles after incubation of cells with tritiated analogs.
      Results show that cells expressing the HSV-TK gene are more sensitive than the
      parent cells to the effect of acyclovir or ganciclovir, the reference purine
      analog drugs, and also to the effect of pyrimidine analogs, bromodeoxyuridine,
      bromovinyldeoxyuridine, and ethyldeoxyuridine. Promising nucleoside analogs for
      gene therapy that can be achieved by HSV-TK could be evaluated using this model.

PMID- 9034633
TI  - Increase of cytochrome P-450 1A and glutathione transferase transcripts in
      cultured hepatocytes from dogs, monkeys, and humans after cryopreservation.
AB  - The study was designed to investigate the effects of phenobarbital (PB), 3
      methylcholanthrene (3-MC), and oltipraz (OPZ), a synthetic derivative of 1,2
      dithiole-3-thione, on the levels of cytochrome P450 1A1/2 and gluthathione
      transferase (GST) mRNAs in both fresh and cryopreserved human, monkey, and dog
      hepatocytes in primary culture. GST alpha mRNAs were demonstrated in liver
      parenchymal cells from the three species: after 4 days of culture, their basal
      levels were decreased, but were strongly higher in PB- and OPZ-treated cells from
      the three species. In contrast 3-MC was mostly effective on human hepatocytes.
      The increased levels of GST alpha mRNAs in the presence of PB or OPZ were not
      observed in all cell populations. GST mu mRNAs, which were detected in both dog
      and monkey hepatocytes, were induced only in the presence of OPZ. GST pi mRNAs
      were expressed in dog hepatocytes but did not respond to any of the inducers. In
      all cases, similar effects were observed in fresh and thawed hepatocytes.
      Similarly, CYP1A1/2 transcripts were induced by 3-MC in both fresh and
      cryopreserved cells from the three species but also after OPZ treatment for
      monkey hepatocytes. These findings demonstrate that enzymes which play a major
      role in bioactivation/detoxication of xenobiotics remain expressed and inducible
      in hepatocytes from various species after cryopreservation and thawing.

PMID- 9034634
TI  - Specific detection of RNA molecules by fluorescent in situ hybridization in
      living cells.
AB  - The antisense therapeutic strategy makes the assumption that sequence-specific
      hybridization of an oligonucleotide to its target can take place in living cells.
      The present work provides a new method for the detection of intracellular RNA
      molecules using in situ hybridization on living cells. The first step consisted
      in designing nonperturbant conditions for cell permeabilization using
      streptolysin O. In a second step, intracellular hybridization specificity was
      evaluated by incorporating various types of fluorescently labeled nucleic acid
      probes (plasmids, oligonucleotides). Due to its high expression level, the 28S
      ribosomal RNA was retained as a model. Results showed that: (1) no significant
      cell death was observed after permeabilization; (2) on living cells, 28S RNA
      specific probes provided bright nucleoli and low cytoplasmic signal; (3) control
      probes did not lead to significant fluorescent staining; and (4) comparison of
      signals obtained on living and fixed cells showed a colocalization of observed
      fluorescence. These results indicate the feasibility of specific hybridization of
      labeled nucleic acid probes under living conditions, after a simple and efficient
      permeabilization step. This new detection method is of interest for investigating
      the dynamics of distribution of various gene products in living cells, under
      normal or pathological conditions.

PMID- 9034635
TI  - In vitro dynamics of chromatin organization and migration.
AB  - The organization of eukaryotic chromatin is not static but changes as a function
      of cell status during processes such as proliferation, differentiation, and
      migration. DNA quantification has not been used extensively to investigate
      chromatin dynamics in combination with cellular migration. In this context, an
      optimized DNA-specific, nonperturbant method has been developed for studying
      chromatin organization, using the fluorescent vital bisbenzimidazole probe
      Hoechst 33342: this property has been described by Hamori et al. (1980). Computer
      assisted image analysis was used to follow migratory activity and chromatin
      organization of L929 fibroblasts during in vitro wound healing. Cell movements
      were analyzed using an optical flow technique, which consists in the calculation
      of the velocity field of cells and nuclear movements in the frame. This system
      allows the correlation of cell migration and position in the cell cycle. It makes
      it possible to study chromatin dynamics using a quantitative analysis of nuclear
      differentiation reorganization (nuclear texture) and to correlate this with
      migration characteristics. The present system would be of interest for studying
      cell-extracellular matrix interactions using differing substrates, and also the
      migratory response to chemotactic factors. Such a model is a prerequisite for
      gaining better understanding of drug action.

PMID- 9034636
TI  - The vital role of papillary muscles in mitral and ventricular function:
      echocardiographic insights.
AB  - The two left ventricular (LV) papillary muscles are small structures but are
      vital to mitral valve competence. Partial or complete rupture, complicating acute
      myocardial infarction, causes severe or even catastrophic mitral regurgitation,
      potentially correctable by surgery. Papillary muscle dysfunction is a
      controversial topic in that the role of the papillary muscle itself, in causing
      mitral regurgitation post infarction, has been seriously questioned; it is less
      confusing if this syndrome is attributed not only to papillary muscle but also to
      adjacent LV wall ischemia or infarction. Papillary muscle calcification is easily
      and frequently detected on echocardiography, but its clinical significance
      remains uncertain. Papillary muscle hypertrophy accompanies LV hypertrophy of
      varied etiology and may have a significant role in producing dynamic late
      systolic intra-LV obstruction in hypertrophic cardiomyopathy and other
      hyperdynamic hypertrophied LV chambers. All the above abnormalities can be
      adequately assessed by 2-D echocardiography and the Doppler modalities. In
      selected cases, transesophageal echocardiography can provide additional valuable
      data by improving visualization of papillary muscles and mitral apparatus.

PMID- 9034637
TI  - Percutaneous transvenous mitral commissurotomy versus surgical commissurotomy in
      the treatment of mitral stenosis.
AB  - There is no doubt that percutaneous transvenous mitral commissurotomy (PTMC) in
      experienced centers is associated with a low risk of major complications and
      yields excellent immediate and long-term outcome. Although previous observational
      studies on both PTMC and surgical commissurotomy have indicated similar outcome
      between the two treatment strategies in terms of valve area improvement and risk
      of major complication (death, thromboembolism and significant resultant mitral
      regurgitation), it was not until recently that several prospective randomized
      trials comparing the two procedures and involving > 470 patients with favorable
      valve characteristics (pliable, noncalcified valve with mild subvalvular disease
      and no or mild mitral regurgitation), have confirmed that PTMC is indeed just as,
      if not more, effective as surgical commissurotomy. The late restenosis rate at up
      to 3-year follow-up appears comparable. Furthermore, PTMC has other additional
      benefits. It is nontraumatic, may be repeated without additional risk, and has
      been shown to be an extremely useful and efficacious palliative tool in those
      with end-stage mitral stenosis or with unfavorable valve anatomy who refuse
      surgery, and in certain subset of patients at high surgical risk because of
      medical comorbidities.

PMID- 9034638
TI  - Effect of amiodarone on QT dispersion in the 12-lead standard electrocardiogram
      and its significance for subsequent arrhythmic events.
AB  - BACKGROUND AND HYPOTHESIS: QT dispersion, measured as interlead variability of QT
      intervals in the surface electrocardiogram, has been demonstrated to provide an
      indirect measurement of the inhomogeneity of myocardial repolarization. The
      purpose of the present study was twofold: (1) to analyze the effect of amiodarone
      on QT dispersion measured in the 12-lead standard ECG, and (2) to examine the
      association between QT dispersion on amiodarone and subsequent arrhythmic events.
      METHODS: To determine the effect of amiodarone on QT dispersion and its clinical
      significance for subsequent arrhythmic events, QT dispersion was measured in the
      12-lead standard electrocardiogram (ECG) in 52 patients before and after
      administration of empiric amiodarone for ventricular tachyarrhythmias. RESULTS:
      QT intervals increased from 401 +/- 44 ms before amiodarone to 442 +/- 53 ms
      after amiodarone therapy, and rate corrected QT intervals (QTc) increased from
      452 +/- 43 ms to 477 +/- 37 ms, respectively (p < 0.01). QT dispersion, QTc
      dispersion, and adjusted QTc dispersion, which take account of the number of
      leads measured, were not significantly different before and after initiation of
      amiodarone therapy (58 +/- 24 ms vs. 61 +/- 26 ms, 68 +/- 29 vs. 66 +/- 26 ms,
      and 22 +/- 8 vs. 22 +/- 8 ms, respectively, p = NS). During 31 +/- 25 months
      follow-up after initiation of amiodarone therapy, arrhythmic events defined as
      sustained ventricular tachycardia, ventricular fibrillation, or sudden death
      occurred in 11 of 52 study patients (21%). QT dispersion, QTc dispersion, and
      adjusted QTc dispersion on amiodarone were not different between patients with
      and without arrhythmic events during follow-up (65 +/- 14 vs. 59 +/- 29 ms, 73 +/
      15 vs. 64 +/- 28 ms, and 25 +/- 6 vs. 21 +/- 8 ms, respectively, p = NS).
      CONCLUSIONS: We conclude that (1) amiodarone increases QT intervals and QTc
      intervals during sinus rhythm but does not significantly change measures of QT
      dispersion; and (2) QT dispersion measured in the 12-lead standard ECG after
      initiation of amiodarone therapy does not appear to be a useful marker for
      subsequent arrhythmic events.

PMID- 9034640
TI  - Transvenous defibrillator systems implanted by electrophysiologists in the
      catheterization laboratory.
AB  - BACKGROUND: A significantly lower perioperative mortality has established the
      nonthoracotomy approach as the preferred technique in implantable cardioverter
      defibrillation (ICD) implantation. With the currently available transvenous
      endocardial leads in combination with the expanded use of biphasic ICD devices,
      the need for use of an additional subcutaneous lead has almost been eliminated.
      Thus, implantation of these systems has been simplified and reports have appeared
      in the literature that the procedure can now be performed by an
      electrophysiologist alone without surgical assistance in the electrophysiology or
      catheterization laboratory. HYPOTHESIS: The purpose of this study was to
      investigate the feasibility and safety of ICD implantation by an
      electrophysiologist in a procedure performed entirely in the catheterization
      laboratory without the assistance of a surgeon. METHODS: Over a period of 28
      months, we implanted transvenous ICDs in 40 consecutive patients with (n = 34)
      and without (n = 6) use of general anesthesia in the catheterization laboratory
      with minor surgical assistance in abdominal pocket fashioning for the first two
      cases and then working alone for the remainder. The study included 36 men and 4
      women, aged 59 +/- 12.5 years, with coronary artery (n = 22) or valvular heart
      disease (n = 4), cardiomyopathy (n = 12), and long QT syndrome (n = 1) or
      idiopathic ventricular tachycardia (n = 1), and a mean left ventricular ejection
      fraction of 34%, who presented with ventricular tachycardia (n = 30) or
      ventricular fibrillation (n = 10). RESULTS: One-lead ICD systems (Endotak, n =
      21; Transvene, n = 8; or EnGuard, n = 1) were used in 30 patients, and 2-lead
      (EnGuard, n = 5 or Transvene, n = 5) systems in 10 patients. Generators were
      implanted in an abdominal (n = 17) or pectoral (n = 23) pocket. Active can
      devices were employed in 17 patients. The defibrillation threshold averaged 9 J.
      All implants were entirely transvenous with no subcutaneous patch. Biphasic ICD
      devices were employed in all patients. There were three complications (8%); one
      pulmonary edema that responded to drug therapy, one lead insulation break that
      required reoperation on the third day, and one pocket hematoma in a patient
      receiving anticoagulation, with no need for evacuation. There were no operative
      deaths and no infections. After implant, patients were discharged at a mean of 3
      days. All devices functioned well at predischarge testing. During follow-up (12
      +/- 8 months), 20 patients received appropriate and 5 patients inappropriate
      shocks. Three patients died of pump failure at 3, 7, and 19 months, respectively;
      they had received 0, 42, and 15 appropriate shocks, respectively, over these
      months. Another patient succumbed to a myocardial infarction at 9 months. At 6
      months, one patient developed subacute subclavian vein thrombosis which resolved
      with anticoagulation therapy. CONCLUSIONS: Current transvenous biphasic ICD
      systems allow experienced electrophysiologists to implant them safely alone in
      the catheterization laboratory without surgical assistance, even for abdominal
      implants, with a high success rate and no need for use of a subcutaneous patch.

PMID- 9034639
TI  - Safety of a new transpulmonary echocontrast agent (Albunex) in repeated
      echocardiographic studies in patients.
AB  - BACKGROUND AND HYPOTHESIS: Multiple contrast-enhanced echocardiographic studies
      are to be expected in patients with cardiac ischemic disease, but the sonication
      process used to produce the echocontrast agent Albunex may result in new epitopes
      that could cause an immunogenic response. METHODS: Repeated exposures to
      intravenous Albunex over a period of time long enough to allow development of an
      eventual immune reaction were performed in 12 patients while monitoring for
      lymphocyte transformation, microsphere specific IgE and IgG antibodies, and
      systemic, pulmonary artery, capillary wedge, and right atrial pressures, as well
      as cardiac output, left ventricular fractional shortening, and blood gases.
      RESULTS: No significant 3H-thymidine incorporation and thus no specific blastic
      transformation of the patients' lymphocytes were observed either for high or low
      Albunex concentrations, corresponding to the expected hepatic and plasma
      concentrations of microspheres. No formation of microsphere-specific IgE and IgG
      antibodies was observed after the first or second Albunex exposure. Furthermore,
      no clinically significant hemodynamic or respiratory adverse reactions were
      observed in any patient. CONCLUSION: These results suggest that repeated
      exposures to intravenous Albunex induce no adverse effect on the cellular and
      humoral immune systems and on left and right heart hemodynamics in patients.

PMID- 9034641
TI  - Surgery in patients with coronary artery disease--silent ischaemia during
      transurethral resection of tumors of prostate or bladder.
AB  - BACKGROUND: Asymptomatic episodes of myocardial ischemia in clinically stable
      patients seem to occur frequently and may hint at a worse prognosis. HYPOTHESIS:
      This study was undertaken to determine whether surgical patients with coronary
      artery disease (CAD) have a higher risk of cardiac ischemia during the
      perioperative period compared with the late postoperative period and compared
      with patients without CAD. METHODS: In all, 14 patients with and 14 patients
      without CAD were examined by Holter monitoring during the perioperative and three
      days later during the postoperative periods for the presence of ST-segment
      depression as a marker of silent myocardial ischemia. RESULTS: While patients
      without CAD did not show ST-segment depression, patients with CAD were found to
      have had 143 episodes of ST-segment depression, 49% in the perioperative and 51%
      in postoperative recordings. CONCLUSION: Though patients were asymptomatic with
      antianginal therapy, there were episodes of ST-segment depression indicating
      silent myocardial ischemia in patients with CAD. Surgical interventions such as
      transurethral resection of tumors of prostate or bladder did not produce an
      increase of ischemic burden registered by Holter monitoring.

PMID- 9034642
TI  - Effect of antibiotic treatment on vegetation size and complication rate in
      infective endocarditis.
AB  - BACKGROUND: Infective endocarditis is associated with significant morbidity and
      mortality, with valvular destruction, and with congestive heart failure. Embolic
      events are more common in patients with echocardiographically discernible
      vegetations, especially when vegetations are > 10 mm in diameter. HYPOTHESIS: The
      objective of the study was to follow vegetation morphology during native valve
      endocarditis, to compare it with the clinical course and antibiotic treatment
      chosen, and to evaluate whether the impact on vegetation size and complication
      rate of antibiotic regimens differed in patients with positive and negative blood
      cultures. METHODS: The effect of different antibiotic regimes on vegetation size
      monitored by using transesophageal echocardiography was evaluated in 183 patients
      with echocardiographic evidence of infective endocarditis. A total of 223
      vegetations attached to the aortic or mitral valves were detected using the
      transesophageal approach. The patients were followed for a mean of 76 weeks and
      underwent a minimum of two consecutive transesophageal echocardiographic
      examinations. RESULTS: Treatment with different kinds of antibiotics corresponded
      with significant differences in vegetation size; vancomycin-associated treatment
      was related to a 45% reduction, ampicillin to a 19% reduction, penicillin to a 5%
      reduction, penicillase-resistant drugs to a 15% increase, and cephalosporin to a
      40% increase in vegetation size. Multivariate analysis showed that penicillin,
      cephalosporin, and penicillase-resistant drug treatments were associated with an
      increased embolic risk, vancomycin treatment with abscess formation, and
      cephalosporin medication with increased mortality. Plotting changes in vegetation
      size against the incidence of embolism and mortality, linear regression analysis
      suggested a 40-50% reduction in vegetation size, thereby greatly reducing the
      risk of embolism and mortality. CONCLUSION: Our study shows that different
      antibiotics have different effects on vegetation size. The highest complication
      rate was observed when vegetations significantly increased in size during
      antibiotic treatment. Especially in culture-negative patients, monitoring
      vegetation size by means of transesophageal echocardiography may prove to be
      useful for estimating the efficacy of antibiotic treatment.

PMID- 9034643
TI  - May age onset be relevant in the occurrence of left ventricular hypertrophy in
      Friedreich's ataxia?
AB  - BACKGROUND: Although heart involvement has been widely reported in Friedreich's
      ataxia (FA), which is the most prevalent of the spino-cerebellar degenerative
      diseases, the reason that cardiac abnormalities develop has not been yet
      established. HYPOTHESIS: The investigation was undertaken to study the prevalence
      and characteristics of cardiac abnormalities in patients with FA and to evaluate
      whether the presence of left ventricular hypertrophy could be predicted. METHODS:
      In all, 75 patients with FA and 16 patients with late onset FA (LOFA) disease
      were investigated for cardiac abnormalities using noninvasive methods. RESULTS: A
      significant (p < 0.01) difference in the age onset (9.8 +/- 3.9 years) was found
      in 31 of the 75 patients with FA (41%) who showed left ventricular hypertrophy
      (LVH) at echocardiographic examination compared with the remaining 44 patients
      with FA without LVH (12.6 +/- 4.3 years). Moreover, none of the 16 patients with
      LOFA (age onset 26.5 +/- 4.2 years) showed abnormalities at echocardiographic
      examination. A significant (p < 0.01) concordance in the familial distribution of
      hypertrophy was also found. CONCLUSION: These data suggest that the earlier the
      disease develops the more frequently LVH occurs.

PMID- 9034645
TI  - Coronary artery and saphenous vein graft remodeling: a review of histologic
      findings after various interventional procedures--Part VI.
AB  - Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of
      acutely and chronically obstructed coronary artery vessels. It is also the
      centerpiece for various new intervention techniques. Their morphologic effects on
      the site of obstruction has been termed "remodeling." Part VI of this six-part
      series focuses on atherectomy and restenosis tissue obtained by atherectomy
      procedures.

PMID- 9034644
TI  - Disparity between serotonin- and acetylcholine-provoked coronary artery spasm.
AB  - BACKGROUND AND HYPOTHESIS: Intrinsic vasoactive substances, such as serotonin and
      acetylcholine, are known to provoke coronary artery spasm in patients with
      vasospastic angina. It remains unclear, however, whether these different agents,
      which activate different receptors, produce spasms at the same sites in these
      patients. The present study was designed to clarify the disparity of receptor
      agonist-induced coronary artery spasms in the same patients. METHODS: We
      conducted sequential provocative tests of coronary artery spasm by acetylcholine,
      serotonin, and ergonovine in 20 patients with rest angina examined with
      quantitative coronary angiography. RESULTS: Coronary artery spasms were provoked
      in all patients at 27 spastic sites. In 13 patients, ergonovine provoked spasms
      and in 10 of 13 patients who were diagnosed with variant angina, both
      acetylcholine and serotonin provoked spasms at the same sites where ergonovine
      also did. In 4 of 13 patients, spasms were provoked by serotonin but not by
      acetylcholine. In the remaining seven patients, whose spasms were induced by
      ergonovine, spasms were produced by acetylcholine but not by serotonin. On
      coronary angiography, the spastic sites for both acetylcholine and serotonin, and
      those for serotonin alone, were located in the proximal segments of coronary
      arteries, whereas the spastic sites for acetylcholine alone were located in the
      distal segments. CONCLUSIONS: This study documented the disparity between
      serotonin- and acetylcholine-induced spasms. Provocative tests using agents that
      activate different receptors may produce coronary artery spasms at the same
      and/or different sites, and this disparity may reflect the clinical heterogeneity
      of vasospastic ischemic syndrome.

PMID- 9034646
TI  - Clinical relevance of heart rate variability.
AB  - Heart rate variability (HRV) has recently become a popular noninvasive research
      tool in cardiology. Clinical assessment of HRV is frequently based on standard
      long-term ambulatory electrocardiograms, whereas physiologic studies employ
      spectral analysis of short-term recordings under controlled conditions. From a
      general point of view, HRV can be used in clinical practice to estimate (1) the
      integrity of cardiac autonomic innervation, (2) the physiologic status of cardiac
      autonomic activity, and (3) the vulnerability to various cardiac arrhythmias
      resulting from autonomic imbalance. Clinical relevance of HRV has been clearly
      demonstrated in only two clinical conditions: (1) impaired HRV can be used alone
      or in a combination with other factors to predict risk of arrhythmic events after
      acute myocardial infarction, and (2) decrease in HRV is a useful clinical marker
      for evolving diabetic neuropathy. Substantial advances of our knowledge are
      required to establish and promote clinical applications in other areas of
      clinical medicine. To accomplish this task, proper hypotheses should be studied
      and appropriate techniques selected.

PMID- 9034647
TI  - Catheter ablation of ventricular tachycardia in Chagasic Cardiomyopathy.
AB  - There is a limited experience with catheter ablation for treatment of ventricular
      tachycardia (VT) in Chagasic cardiomyopathy. A 30-year-old woman experienced
      episodes of palpitations and syncope due to attacks of VT. A diagnosis of Chagas
      disease was established on a biological basis. Two-dimensional echo and contrast
      ventriculography showed an apical aneurysm with thrombus. Surgery was indicated
      to resect the aneurysm and ablate the VT. Ventricular tachycardia recurred 1
      month later despite therapy, including amiodarone. Two clinical frequent and well
      tolerated tachycardias were identified. The site of origin was located in the
      right ventricular apex and in the apical-lateral wall of the left ventricle,
      respectively. Catheter ablation was performed at two sites with DC shocks (total
      energy 600 J) after unsuccessful radiofrequency ablation. Holter recordings
      performed during the post-operative period showed only infrequent extrasystoles.
      After follow-up of 24 months the patient remains asymptomatic. Drug-refractory VT
      in Chagasic cardiomyopathy can be ablated by medium-energy DC shocks after
      failure of radiofrequency ablation.

PMID- 9034648
TI  - Echocardiographic diagnosis of papillary fibroelastoma of the mitral and
      tricuspid valve apparatus.
AB  - Papillary fibroelastomas are rare and normally benign cardiac tumors typically
      attached to cardiac valves. This report describes two patients who were evaluated
      for intermittent dyspnea in one case and for the source of cerebral embolism in
      the other. In both patients transthoracic echocardiography revealed a
      pedunculated mobile mass adjacent to an atrioventricular valve, suggestive of
      papillary fibroelastoma. Postoperative histology was confirmatory of papillary
      fibroelastoma with a typical hyalinized hypocellular stroma covered by a single
      layer of endocardial cells.

PMID- 9034649
TI  - Enhanced external counterpulsation as an adjunct to revascularization in unstable
      angina.
AB  - Enhanced external counterpulsation (EECP) is an effective noninvasive treatment
      for chronic stable angina. Despite intensive risk factor modification, a patient
      required two surgical coronary revascularizations and seven multivessel
      angioplasties over a 26-month period, demonstrating recurrent unstable angina and
      persistent thallium perfusion defects despite revascularization. Post EECP,
      angina was relieved, thallium defects were resolved and the patient has remained
      asymptomatic for 36 months.

PMID- 9034650
TI  - Lorenzo Bellini.

PMID- 9034651
TI  - Physiology of the skin--differences between women and men.

PMID- 9034652
TI  - Genodermatoses in women.

PMID- 9034653
TI  - Perimenstrual eruptions.

PMID- 9034654
TI  - Physiological changes in the skin during pregnancy.

PMID- 9034656
TI  - Dermatologic diseases of the vulva.

PMID- 9034655
TI  - Dermatologic diseases of the breast in young women.

PMID- 9034658
TI  - Genital herpes simplex infection in women.

PMID- 9034657
TI  - Human papillomavirus infection in women. Special aspects of infectious diseases
      in women.

PMID- 9034659
TI  - Human immunodeficiency virus in women: mucocutaneous manifestations.

PMID- 9034660
TI  - Hair problems in women.

PMID- 9034661
TI  - Psychodermatology of women.

PMID- 9034662
TI  - Dermatologic problems of the menopause.

PMID- 9034663
TI  - Cutaneous complications of hormonal replacement therapy.

PMID- 9034664
TI  - Lichen sclerosus in women.

PMID- 9034666
TI  - An algorithm for real-time vessel enhancement and detection.
AB  - In this paper we present an algorithm for the real-time enhancement and detection
      of blood vessels in medical images. The algorithm is based on a set of linear
      filters sensitive to vessels of different orientation and thickness. Such filters
      are obtained as linear combinations of properly shifted Gaussian kernels. The
      output of multiple oriented vessel-enhancing filters can be integrated to obtain
      images in which vessels are highly enhanced independently of their direction and
      thickness. To avoid spurious responses in the presence of step edges or to
      enhance the skeletons of vessels, the output of directional filters can be
      validated before integration. Skeleton detection and vessel segmentation can be
      performed via thresholding with hysteresis. Experimental results on synthetic
      images and real coronary arteriograms are reported.

PMID- 9034665
TI  - Tropical diseases and women.

PMID- 9034667
TI  - Lossless ECG encoding.
AB  - We have studied the lossless encoding of ECG signals. With suitable code we aim
      to reduce the storage space needed by ECG signals. Several methods designed for
      ECG compression use lossy, i.e. irreversible techniques, in which the original
      signal is lost, but the restored approximation is almost equal to the original.
      We aimed, however, to use reversible methods which are able to restore the
      original signal exactly. We have examined various methods and developed a new
      approach based on structural recognition and extraction of ECG complexes.
      Comparative conclusions are drawn from the compression efficiency of lossless and
      lossy methods. In this study, the effect of sampling frequency, resolution and
      filtering is also examined.

PMID- 9034668
TI  - DSP implementation of wavelet transform for real time ECG wave forms detection
      and heart rate analysis.
AB  - An algorithm based on wavelet transform (WTs) suitable for real time
      implementation has been developed in order to detect ECG characteristics. In
      particular, QRS complexes, P and T waves may be distinguished from noise,
      baseline drift or artefacts. This algorithm is implemented in a DSP (SPROC-1400)
      with a 50 MHz frequency clock. The performance of this algorithm is discussed,
      its accuracy is evaluated and a comparison is made with a similar algorithm
      implemented in C language. For the standard MIT/BIH arrhythmia database, this
      algorithm correctly detects 99.7% of the QRS complexes.

PMID- 9034669
TI  - Simulation with EGS4 code of external beam of radiotherapy apparatus with
      workstation and PC gives similar results?
AB  - This article presents a comparison between two implementations of an EGS4 Monte
      Carlo simulation of a radiation therapy machine. The first implementation was run
      on a high performance RISC workstation, and the second was run on an inexpensive
      PC. The simulation was performed using the MCRAD user code. The photon energy
      spectra, as measured at a plane transverse to the beam direction and containing
      the isocenter, were compared. The photons were also binned radially in order to
      compare the variation of the spectra with radius. With 500,000 photons recorded
      in each of the two simulations, the running times were 48 h and 116 h for the
      workstation and the PC, respectively. No significant statistical differences
      between the two implementations were found.

PMID- 9034670
TI  - A software for the description of workplaces in the PRS system.
AB  - Workplace description is an operation indispensable for the identification of
      professional risks and, in fulfillment of that objective, can best be
      accomplished by listing the constituent tasks associated with each job. This
      article presents a software in Visual-Basic to be run on a portable micro
      computer, which facilitates this process according to these aims. The
      occupational physician and safety engineer can make good use of the exposure
      database resulting from the application of this program. Job histories are built
      automatically, while workers with similar exposures are grouped together and job
      exposure matrices are elaborated. This information, computerized, sorted and re
      assembled, can then be used effectively for studies in the field of occupational
      epidemiology.

PMID- 9034671
TI  - Comprehensive life table of computer-assisted predictive mathematical
      relationship between age and life expectancy, survival probability or death rate
      in US adults.
AB  - A microcomputer program in BASIC for predicting life expectancy by age in US
      adults was designed. Formulas used in this study were derived from the data
      reported by the National Center for Health Statistics. A comprehensive life table
      that shows the relationship between age and death rate, survival probability or
      life expectancy for each year between 25 and 85 years of age was obtained in this
      study, using a newly designed computer program for predicting life expectancy by
      age and the program for survival probability previously published by the author.
      The comprehensive life table may be useful for clinical evaluation of patients
      and further helpful for biomedical investigation and epidemiological evaluation
      of US adults.

PMID- 9034672
TI  - NEUROLAB, a PC-program for the processing of neurobiological data.

PMID- 9034673
TI  - The conceptual design of a radiation oncology planning system.
AB  - The conceptual design of a three-dimensional, radiation oncology planning system
      is described. To assure that clinical needs were met, the working routines in two
      major Swedish radiation oncology departments were analysed in detail. Generic
      work flow was identified and mapped and compared to those in other institutions.
      The flow was partitioned into a number of nodes that together formed a basis for
      the design of the system handling logistics. The design criteria of this system
      emphasised accommodation of current clinical practice and traditional treatment
      modalities, and facilitated means to validate the computational techniques. The
      system should also allow for new procedures and was based on the analysis of
      current practice and a synthetic idea of how 3D treatment planning should be
      done. The final product supports the treatment planning work in its entirety. It
      is believed that the techniques followed are of interest to those engaged in
      computer systems of similar purposes and complexities.

PMID- 9034674
TI  - An artificial neural network system for diagnosis of acute myocardial infarction
      (AMI) in the accident and emergency department: evaluation and comparison with
      serum myoglobin measurements.
AB  - Recent studies have confirmed that artificial neural networks (ANNs) are adept at
      recognising patterns in sets of clinical data. The diagnosis of acute myocardial
      infarction (AMI) in patients presenting with chest pain remains one of the
      greatest challenges in emergency medicine. The aim of this study was to evaluate
      the performance of an ANN trained to analyse clinical data from chest pain
      patients. The ANN was compared with serum myoglobin measurements--cardiac damage
      is associated with increased circulating myoglobin levels, and this is widely
      used as an early marker for evolving AMI. We used 39 items of clinical and ECG
      data from the time of presentation to derive 53 binary inputs to a back
      propagation network. On test data (200 cases), overall accuracy, sensitivity,
      specificity and positive predictive value (PPV) of the ANN were 91.8, 91.2, 90.2
      and 84.9% respectively. Corresponding figures using linear discriminant analysis
      were 81.0, 77.9, 82.6 and 69.7% (P < 0.01). Using a further test set from a
      different centre (91 cases), the accuracy, sensitivity, specificity and PPV for
      the admitting physicians were 65.1, 28.5, 76.9 and 28.6% respectively compared
      with 73.6, 52.4, 80.0 and 44.0% for the ANN. Although myoglobin at presentation
      was highly specific, it was only 38.0% sensitive, compared with 85.7% at 3 h.
      Simple strategies to combine clinical opinion, ANN output and myoglobin at
      presentation could greatly improve sensitivity and specificity of AMI diagnosis.
      The ideal support for emergency room physicians may come from a combination of
      computer-aided analysis of clinical factors and biochemical markers such as
      myoglobin. This study demonstrates that the two approaches could be usefully
      combined, the major benefit of the decision support system being in the first 3 h
      before biochemical markers have become abnormal.

PMID- 9034675
TI  - A computer program to aid in visual concept development in dentistry.
AB  - Beginning dental students normally receive their first exposure to the study of
      tooth forms (morphology) through a dental anatomy laboratory course in which they
      are required to reproduce tooth morphology, usually with wax. The fabrication of
      a tooth in wax requires proper visual recognition skills and fine eye-hand
      coordination. Many students struggle with one or both of these. A computer
      program, designed to teach recognition concepts, was delivered to three groups of
      beginning freshman dental students in conjunction with their dental anatomy
      laboratory course while a group of their classmates served as the controls. This
      study investigated (1) instructional design and interface improvement and (2) the
      best method to implement the computer program. Experimental and control groups
      all received normal daily critiques of their course project work. After
      completion of the computer program, all groups were tested with a recognition
      based examination as well as with a practical examination, requiring the
      reproduction of a tooth in wax. All experimental groups scored better than the
      control group on both examinations. Results indicated that computer-based
      instruction may be a useful means to foster visual concept development. An
      expanded program, using better graphics, animation and movies is currently under
      development.

PMID- 9034676
TI  - A case-based consiliarius for therapy recommendation (ICONS): computer-based
      advice for calculated antibiotic therapy in intensive care medicine.
AB  - We report here on the system ICONS which utilizes case-based reasoning for
      medical decision support. As an application domain we have chosen the medical
      field of 'calculated antibiotic therapy' in an intensive care medicine setting.
      The system ICONS which runs on a personal computer suggests adequate antibiotic
      therapy regimen satisfying medical and economic conditions. To speed up the
      process of finding an adequate antibiotic therapy for a current patient, case
      based reasoning is used for finding previously documented similar cases and for
      modifying them according to the requirements of the current patient. To reduce
      the memory capacity for the documentation of cases, collections of similar cases
      are clustered to prototypes. Medical knowledge is represented within a hierarchy
      of such prototypes and cases and an additional context-sensitive background
      knowledge-base. A knowledge acquisition tool was programmed that allows revisions
      of the background medical knowledge-base by simple and comprehensive methods. In
      addition to the advantage of producing site-specific and time-dependent
      knowledge, case-based reasoning is a practical method for speeding-up the process
      of generating and evaluating hypotheses in medical classification tasks.

PMID- 9034677
TI  - Automated generation of a World Wide Web-based data entry and check program for
      medical applications.
AB  - The World Wide Web-based form is a promising method for the construction of an on
      line data collection system for clinical and epidemiological research. It is,
      however, laborious to prepare a common gateway interface (CGI) program for each
      project, which the World Wide Web server needs to handle the submitted data. In
      medicine, it is even more laborious because the CGI program must check deficits,
      type, ranges, and logical errors (bad combination of data) of entered data for
      quality assurance as well as data length and meta-characters of the entered data
      to enhance the security of the server. We have extended the specification of the
      hypertext markup language (HTML) form to accommodate information necessary for
      such data checking and we have developed software named AUTOFORM for this
      purpose. The software automatically analyzes the extended HTML form and generates
      the corresponding ordinary HTML form, 'Makefile', and C source of CGI programs.
      The resultant CGI program checks the entered data through the HTML form, records
      them in a computer, and returns them to the end-user. AUTOFORM drastically
      reduces the burden of development of the World Wide Web-based data entry system
      and allows the CGI programs to be more securely and reliably prepared than had
      they been written from scratch.

PMID- 9034678
TI  - An image capture and communication system for emergency computed tomography.
AB  - An image capture and communication system for emergency computed tomography (CT)
      is presented. The system, named ICCS, integrates CT scanners, personal computers
      (PC), network systems, an IBM API gateway and an IBM mainframe platform. The ICCS
      was implemented in the emergency unit in the Taichung Veterans General Hospital
      (TCVGH) and has received considerable support from the doctors, nurses and staff
      of the TCVGH emergency unit who have shown great interest in ICCS. This is
      because ICCS allows physicians in the emergency unit to examine patients' images
      on image viewing stations immediately after the patients are CT scanned. It also
      makes remote consultation possible for doctors who can stay where they are and
      consult with radiologists through the system and a hot line without leaving the
      emergency unit. This advantage greatly reduces the consultation time and saves
      many unnecessary trips between the emergency unit and the Department of
      Radiology.

PMID- 9034679
TI  - Exposure of nickel in used and unused gold-plated earrings: a study using
      scanning electron microscopy and X-ray microanalysis.
AB  - Nickel is the most common contact sensitizer in the female population. The aim of
      the present study was to examine closely the surface of both used and unused gold
      plated earrings by scanning electron microscopy, and to ascertain the
      distribution of nickel on the surface of these earrings qualitatively and
      quantitatively by X-ray microanalysis. The claps of 4 sets of used earrings
      causing nickel dermatitis and of the 3 sets of unused earrings were examined. In
      backscattered electron images obtained by scanning electron microscopy, a large
      number of scratches and pits were found on the surface of the used earrings.
      Cross-sections of the surfaces confirmed that the gold plating was defective in
      some areas, exposing the nickel. Nickel was readily detected and quantitatively
      determined in the scratches and pits by X-ray microanalysis. We also found that,
      even in unused earrings, numerous scratch marks and pits were present, again
      exposing the nickel. Clearly, even in unused earrings, nickel exposed at the
      surface sensitizes the skin and causes contact dermatitis.

PMID- 9034680
TI  - Olive oil--contact sensitizer or irritant?
AB  - Adverse cutaneous reactions to topically applied olive oil are seldom reported,
      and positive patch tests to it are mostly regarded as allergic. To evaluate such
      "positive" patch test reactions, 77 female (mean age: 44 years) and 23 male
      eczema patients (mean age: 46 years) were prospectively patch tested with freshly
      prepared olive oil. Tests were performed openly (including ROAT) as well as using
      Al-tests and Finn Chambers on Scanpor. 5 patients (2 male) showed "positive" test
      reactions (all patients at the Al-test site, 3 at the Finn Chamber site, 1 with
      ROAT). In only 1 patient could the reaction be classified as probably allergic,
      in contrast to previous reports. In conclusion, olive oil is very weakly irritant
      in general, but bears relevant irritant capacity when applied under occlusive
      conditions. Therefore, olive oil appears to be less than suitable for the topical
      therapy of patients with venous insufficiency and associated eczema of the lower
      extremities.

PMID- 9034681
TI  - Purpura caused by Emla is of toxic origin.
AB  - Emla cream has been widely used as a local anaesthetic for superficial
      procedures. Blanching and redness are commonly observed side-effects. We observed
      purpura in 5 patients after application of Emla. Other authors have not reported
      this before. In 4 patients, purpura was observed after 30 min Emla application
      before the treatment of mollusca contagiosa. In 1 patient, Emla was used for 60
      min before taking a lip biopsy. In these patients, patch tests were performed
      with the individual ingredients of Emla cream, Emla cream itself, placebo cream,
      and Tegaderm plaster. All tests were negative at an early reading after 30 min as
      well as after 2 and 3 days. We concluded that the purpuric reaction was not of an
      allergic nature. Possibly, it was caused by a toxic effect on the capillary
      endothelium.

PMID- 9034682
TI  - Predictive testing of metalworking fluids: a comparison of 2 cumulative human
      irritation models and correlation with epidemiological data.
AB  - Metalworking fluids (MWF) have been reported as being an important cause of
      irritant contact dermatitis in metal workers. Our purpose was to determine
      whether the irritancy of different MWF assessed by 2 different types of
      predictive human in vivo tests could be compared with epidemiological data. 3
      water-based MWF were tested in the same panel of subjects. Reactions were
      assessed by a visual score (VS), evaporimetry to evaluate the transepidermal
      water loss (TEWL) and chromametry to quantify erythema. Test 1: MWF were applied
      with Finn Chambers on the volunteers' mid-back, removed after 1 day of exposure,
      and reapplied for a further 2 days. Test 2: Cumulative irritant contact
      dermatitis was induced using a repetitive irritation test for 2 weeks (omitting
      weekends) for 6 h per day. We observed an increase in VS, TEWL, and erythema for
      all MWF, with the same irritancy ranking in both test models. Differentiation of
      the substances was better in the D1/D3 test. The experimental results partially
      correlated with the epidemiological data. Considering the shorter application
      time and the better discrimination of irritancy, we prefer the D1/D3 model as a
      predictive test of MWF irritancy. Our results might aid development of a
      standardized test to reduce cumulative skin irritation in metal workers.

PMID- 9034683
TI  - Leukaemia inhibitory factor: induction in the early phase of allergic contact
      dermatitis.
AB  - It has been suggested that leukaemia inhibitory factor (LIF), may be involved in
      the pathogenesis of cutaneous inflammation. In 5 patients with previously proven
      contact allergy to nickel, LIF mRNA and protein expression were assessed by
      reverse transcription-polymerase chain reaction and immunohistochemistry in 5%
      nickel sulfate patch test biopsies 24 h after application of the patch. Control
      specimens were obtained from non-tested and vehicle-tested skin from the same
      individuals. LIF mRNA expression was significantly increased in nickel-tested
      skin compared with both vehicle-tested (p = 0.045) and non-tested skin (p =
      0.041). All biopsies showed similar patterns of LIF immunoreactivity, with no
      significant differences between nickel-tested, vehicle-tested and non-tested
      skin. Immunostaining was cytoplasmic and was present in the epidermis and hair
      follicles. No dermal staining was observed. This study suggests that LIF may play
      a role in the early phase of allergic contact dermatitis.

PMID- 9034684
TI  - Threshold for occluded formaldehyde patch test in formaldehyde-sensitive
      patients. Relationship to repeated open application test with a product
      containing formaldehyde releaser.
AB  - Our purpose was to investigate the eliciting threshold concentration of
      formaldehyde in formaldehyde-sensitive individuals in the occluded and non
      occluded patch test, and to evaluate the relationship to repeated open
      application test (ROAT) with a product containing a formaldehyde releaser. 20
      formaldehyde-sensitive patients and a control group of 20 healthy volunteers were
      included in the study. Occluded and non-occluded patch tests with formaldehyde
      solutions from 25 to 10,000 ppm, and ROAT for 1 week with a leave-on cosmetic
      product containing on average 300 ppm formaldehyde, were carried out
      simultaneously on each subject. In the occluded patch test, 1/2 of the 20
      patients only reacted to 10,000 ppm formaldehyde, 9 reacted to 5,000 ppm, 3
      reacted to 1,000 ppm, 2 reacted to 500 ppm and 1 reacted to 250 ppm. No definite
      positive reactions were observed in the non-occluded patch test or in the ROAT.
      No positive reactions were observed in the control group to any of the test
      procedures. We concluded that the threshold concentration for occluded patch test
      to formaldehyde in formaldehyde-sensitive patients was 250 ppm. The threshold in
      occluded patch test corresponded to the degree of sensitivity. Definite positive
      reactions in the ROAT were not seen, either indicating that they are unlikely to
      happen with the type of product used or that the exposure time was too short.

PMID- 9034686
TI  - A proposed relevance scoring system for positive allergic patch test reactions:
      practical implications and limitations.
AB  - A relevance scoring system for positive allergic patch test reactions is
      proposed. It refers to current relevance (CR) as well as past relevance (PR). The
      system was evaluated in adult patients between January 1 and June 30, 1996, and
      limited to 4 allergens: nickel sulfate, neomycin sulfate, epoxy resin and
      colophony. Certain methods available for increasing the accuracy of relevance
      were used in the present study. Practical implications and limitations of using a
      relevance scoring system are discussed.

PMID- 9034685
TI  - Delayed and immediate allergy caused by methylhexahydrophthalic anhydride.
AB  - Epoxy resin compounds (ERC) include a large number of chemicals, such as epoxy
      resins (ER), reactive diluents and hardeners. Many hardeners, e.g., aliphatic
      polyamines, are well-known sensitizers. Another type of ER hardeners are the
      phthalic anhydrides, such as methylhexahydrophthalic anhydride (MHHPA) and
      methyltetrahydrophthalic anhydride (MTHPA), which have been reported as causing
      immunologically-mediated respiratory diseases and contact urticaria, but not
      allergic contact dermatitis. Here, we present a horizontal boring-machine worker
      who developed allergic contact dermatitis, as well as allergic rhinitis and an
      immediate contact skin reaction from MHHPA. Patch testing with a dilution series
      of MHHPA in pet. elicited the following results: 2%, 1% and 0.5%, +2; 0.25% and
      0.125%, + (3- to 6-day readings). An immunohistochemical and electron microscopic
      study also indicated that the patch test reactions were conventional-delayed
      allergic reactions. Interleukin 8 was observed in the epidermal cells, whereas
      interleukin 4 immunoreactivity was detected in the dermal cells. Immunoreactivity
      to-interleukin 5, granulocyte/macrophage-colophony stimulating factor (GM-CSF) or
      eosinophil cationic protein was not seen. In conclusion, the patient developed
      both Type I and Type IV allergy to MHHPA. The clinical data, patch test results,
      immunohistochemical and electron microscopic observations indicated that the
      MHHPA allergy detected by the patch test reaction was a conventional delayed-type
      hypersensitivity reaction. The patient also had an allergic patch test reaction
      to para-phenylenediamine and diaminodiphenylmethane, possibly representing
      occupational sensitization.

PMID- 9034687
TI  - A case of contact dermatitis due to impurities of cetyl alcohol.
AB  - A 29-year-old man being treated for itchy lesions on the amputation stump of the
      thigh became allergic to betamethasone valerate and gentamicin sulfate cream
      (Rinderon VG). Closed patch tests with all the ingredients of the cream revealed
      positive reactions to cetyl alcohol 30% to 5% pet. Gas chromatographic analysis
      of the cetyl alcohol in the cream base detected stearyl alcohol (C18), myristyl
      alcohol (C14) and lauryl alcohol (C12) in addition to the main component of cetyl
      alcohol (C16). Patch testing with 99% pure analytical reagent grade saturated
      alcohols (C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20) showed negative
      reactions. Thus, it is concluded that some minor impurities in cetyl alcohol not
      detected by gas chromatography might be the cause of this dermatitis.

PMID- 9034688
TI  - Perioperative collapse: prevalence of latex allergy in patients sensitive to
      anaesthetic agents.
AB  - The evidence in the literature suggests that the prevalence of latex allergy in
      the general population is approximately 1%. With increasing awareness of
      transmission of HIV and other infections such as hepatitis B, the use of latex
      gloves and condoms has escalated in recent years. As cheaper latex gloves of
      variable and doubtful quality flood the market, health care workers and patients
      are being increasingly sensitized by these latex products. A retrospective study
      investigated the prevalence of latex allergy in a cohort of 26 patients who
      suffered perioperative anaphylactoid reactions. 84% of these patients were
      hypersensitive to at least 1 anaesthetic-related agent. 7.7% were also allergic
      to latex (p = 0.028). Atopy is a strong predisposing factor (p = 0.006). An
      accurate preoperative history of atopy and past reactions to latex will identify
      most at-risk patients. Prick test and RAST to latex will confirm the latex
      allergy. Anaesthetists, surgeons, allergists and other health practitioners
      should be aware of this problem.

PMID- 9034689
TI  - Allergic contact dermatitis from the fungicide Rondo-M and the insecticide
      Alfacron.

PMID- 9034690
TI  - Contact allergy in monozygous twins.

PMID- 9034691
TI  - Occupational allergic contact dermatitis from 5-chloro-1-methyl-4-nitroimidazole.

PMID- 9034692
TI  - Delayed-type hypersensitivity to mofebutazone underlying a severe drug reaction.

PMID- 9034693
TI  - Seizure adequacy: does EEG hold the key?

PMID- 9034694
TI  - Assessment of mood state in patients undergoing electroconvulsive therapy: the
      utility of visual analog mood scales developed for cognitively impaired patients.
AB  - Reliable, valid, and brief measures of mood state are essential to the evaluation
      of electroconvulsive therapy (ECT) efficacy. However, existing measures of mood
      state may be inappropriate for patients with transient cognitive impairment.
      Stern and colleagues have recently developed a set of Visual Analog Mood Scales
      (VAMS) for use in neurologically impaired patients. These brief scales (including
      measures of sad, confused, afraid, happy, tired, angry, and energetic states) are
      easily administered and have documented reliability and validity in
      neurologically impaired patients and in healthy adult and geriatric samples. In
      the present study, we assessed the validity and sensitivity of the VAMS to detect
      ECT-related mood change. Twenty-five inpatients who were diagnosed with major
      depressive episode and referred for ECT were administered the VAMS and the
      Hamilton Depression Rating Scale (HDRS) both pre- and post-ECT. Results indicate
      that the VAMS are as sensitive to the therapeutic effects of ECT as is the more
      lengthy and verbally demanding HDRS. In addition, the VAMS were highly correlated
      with the clinician's Clinical Global Improvement rating and the patient's self
      report using a modified Center for Epidemiological Studies-Depression scale. The
      VAMS are brief, reliable scales that are sensitive to the treatment effects of
      ECT and that are appropriate for patients with transient cognitive impairment.

PMID- 9034695
TI  - Ictal EEG regularity declines during a course of RUL ECT.
AB  - Twenty depressed patients (4 men, 16 women; mean age 67 years) received right
      unilateral (RUL) electroconvulsive therapy (ECT). The ictal electroencephalogram
      (Fp1-A1) was blindly rated on a 7-point scale for regularity of morphology at
      treatments two, four, and six. Seizure regularity declined during the course of
      ECT.

PMID- 9034696
TI  - Ketamine anesthesia in electroconvulsive therapy.
AB  - The use of ketamine anesthesia in electroconvulsive therapy (ECT) has been
      limited by its effects on blood pressure and concerns about untoward
      psychological reactions. However, because its effect on seizures is presumably
      less than that of methohexital, ketamine is listed as an alternative method to
      prolong seizure length. In this case series, 10 patients were given ketamine
      anesthesia during ECT. Whereas blood pressures were elevated above those seen
      with methohexital, seizure lengths actually decreased nonsignificantly with
      ketamine. There were no adverse psychological reactions noted with ketamine,
      which was generally well tolerated. It is concluded that ketamine anesthesia with
      the doses used in this series is unlikely to be associated with longer seizures
      in ECT. However, for theoretical reasons discussed, ketamine may be worth
      studying further in ECT.

PMID- 9034697
TI  - Polysomnographic studies in patients referred for ECT: pre-ECT studies.
AB  - Forty-one patients referred for electroconvulsive therapy (ECT) were evaluated
      with a standardized clinical protocol and had polysomnographic studies performed
      pre-ECT after 10 or more days drug free. Clinical evaluations were performed by
      blind investigators and included the Research Diagnostic Criteria and the
      Hamilton Rating Scale for Depression (HRSD). Patients were categorized according
      to the clinical response. Thirty patients (73%) reached a post-ECT HRSD < or =
      10, whereas 21 of them (51.2%) reached a post-ECT HRSD score < or = 6. Sleep
      onset rapid eye movement (SOREM) periods were present in 27 (66%) of the
      patients. Few polysomnographic variables differentiated between excellent
      responders and patients with residual symptoms. Older patients had significantly
      more disrupted polysomnographic study parameters. Although present in a
      significant proportion of patients, baseline SOREM was not a factor in outcome.

PMID- 9034698
TI  - Facilitation of ECT by intravenous administration of theophylline.
AB  - Seven patients with major depression who developed seizure inhibition during a
      course of ECT, were given intravenous theophylline to increase seizure duration.
      Infusion of 100-200 mg of theophylline, administered slowly over several minutes
      approximately 30 min before seizure induction, was found to effectively and
      safely prolong seizure durations. In a total of 55 treatment sessions, no
      cardiovascular or other complications were seen. On one occasion, seizure
      duration was prolonged to 220 s.

PMID- 9034699
TI  - Memory functions six to nine months after electroconvulsive therapy. 1975.

PMID- 9034700
TI  - ECT in Parkinson's disease: neuropsychological response.

PMID- 9034701
TI  - Advances in the diagnosis and treatment of catatonia.

PMID- 9034702
TI  - Triazolam and diphenhydramine effects on seizure duration in depressed patients
      receiving ECT.

PMID- 9034712
TI  - Developmental regulation of elastin gene expression.
AB  - Developmental regulation of elastin gene expression appears to be exerted
      primarily at the transcriptional level. Although the elastin gene promoter
      possesses features of "housekeeping" genes, these characteristics do not preclude
      transcriptional regulation as shown with a number of other gene promoters of this
      class. Direct evidence for transcriptional regulation has been obtained by
      nuclear run-on analysis of nuclei isolated from developing lung and aortic
      tissues and indirectly through elastin promoter activity in transgenic mice and
      transient tissue transfections of embryonic lung and aortic tissues. Although
      several different modulators have been proposed to control the developmental
      activation of elastin gene expression, only insulin-like growth factor I has been
      experimentally linked to increased transcription by in vivo studies. This link is
      specific for aortic smooth muscle cells in which cell cycle control appears
      intimately associated with elastogenesis. Recent studies suggest that progress in
      understanding developmental activation of the elastin gene lies in transgenic
      models and organ transfection assays that assess the direct relevancy of the
      modulators and cis- and trans-acting factors involved.

PMID- 9034713
TI  - Regulation and activities of alpha-fetoprotein.
AB  - alpha-Fetoprotein (AFP) is one of the major serum proteins in the early life of
      mammals. The function of this protein is not yet fully understood. AFP is an
      oncodevelopmental gene product which is expressed at high levels in the embryonic
      yolk sac and fetal liver. The synthesis of AFP decreases dramatically after
      birth. Only trace amounts of AFP are synthesized in the adult liver. However,
      expression of the AFP gene is reactivated in the adult during liver regeneration
      and hepatocarcinogenesis. AFP is an excellent model system for studying the
      temporal and tissue-specific regulation of oncodevelopmental gene expression.
      Experiments with transgenic mice and DNA transfection studies have revealed
      several transcriptional control regions and cis-acting elements in the AFP gene.
      A large number of trans-acting protein factors interacting with these cis-acting
      elements have also been identified. Recent studies demonstrated that expression
      of AFP is regulated by at least two major signal transduction pathways in
      response to extracellular stimuli. The interactions between steroid hormone
      receptors and transcriptional factors which respond to separate signal
      transduction pathways result in transcriptional regulation of AFP gene
      expression. Trans-acting protein factors or steroid receptors complexed with
      given response elements can display different activities in different cell types
      due to cross-talk among both local protein-protein interactions within the DNA
      binding domain, and distal protein-protein interactions. However, the detailed
      mechanisms of AFP gene expression are still not completely understood.

PMID- 9034714
TI  - The estrogen receptor activity cycle: dependence on multiple protein-protein
      interactions.
AB  - The estrogen steroid hormone receptor (ER) is a member of a family of related
      hormone-inducible transcriptional regulators. The function of these receptors is
      dependent on multiple protein-protein interactions with other cellular
      polypeptides. These contacts regulate the four steps in the receptor "life
      cycle": synthesis and nuclear transport, priming/storage, activation, and
      recycling. Each of these steps is mediated by the formation of distinct protein
      complexes and results in a temporal and spatial regulation of ER activity. This
      review focuses on the cellular proteins that interact with the ER, and the role
      that these interactions are believed to play in the regulation of ER.

PMID- 9034715
TI  - Molecular mechanisms of nuclear protein transport.
AB  - Transport of proteins into and out of the nucleus occurs through nuclear pore
      complexes (NPC). A heterodimeric protein complex, composed of karyopherin alpha
      and beta (or importin alpha and beta) functions to target proteins containing a
      nuclear localization sequence (NLS) to the NPCs. Two additional proteins, the
      GTPase Ran and p10, are required to translocate the docked NLS protein into the
      nucleus. The alpha subunit of karyopherin functions as the NLS receptor, whereas
      the beta subunit mediates docking to nucleoporins that contain peptide repeats.
      During import the karyopherin heterodimer dissociates: karyopherin alpha and
      import substrates enter and accumulate in the nucleoplasm, whereas karyopherin
      beta accumulates at the nuclear pore complex. Ran-GTP induces dissociation of
      karyopherin alpha from beta by forming a complex with karyopherin beta and
      promotes the release of both karyopherin subunits from a docking site. Protein
      transport across the NPC may occur via guided diffusion involving the karyopherin
      mediated docking and undocking of import substrate to multiple binding sites that
      extend from the cytoplasmic to the nucleoplasmic ends of the NPC.

PMID- 9034716
TI  - Translational control during early development.
AB  - The regulation of gene expression during early development is controlled
      predominantly at the translational level. This becomes necessary due to
      transcriptional arrest during maturation of the oocyte and the rapid early
      cleavage divisions of the embryo. Consequently, early events involved in pattern
      formation, germ cell specification, cell fate, and cell division are programmed
      by maternal messenger ribonucleic acid (RNA). The majority of these transcripts
      are stored as masked ribonucleoproteins particles during oogenesis but undergo
      sequence-specific translational activation during oocyte maturation and
      embryogenesis. Translational regulation occurs in the male germ line and, though
      not a prominent feature, in the soma as well. Evidence suggests that the assembly
      of ribonucleoprotein (RNP) particles may be coupled to transcription. Specific
      translational regulatory sequences are found in the 5' and 3' untranslated
      regions of maternal mRNA, but the majority occur downstream of the coding region.
      Most of the known cis-acting sequences and associated proteins are implicated in
      translational repression. Antisense RNA also has been implicated in specific mRNA
      translational regulation. Although little is known about message-specific
      unmasking, in general, one exception is cytoplasmic polyadenylation-mediated
      translational activation. A widespread phenomenon, it occurs in both vertebrates
      and invertebrates.

PMID- 9034717
TI  - Molecular mechanisms mediating axon pathway formation.
AB  - During nervous system formation nerve cells extend axons in order to form precise
      patterns of neuronal connectivity. These connections are often established after
      the neuronal growth cones have pioneered or navigated through complex pathways to
      their target area both within the CNS and to and from the periphery. Recent
      studies have provided evidence that the process of specific pathway formation may
      rely on a number of molecular guidance mechanisms and cues such as selective
      adhesion, growth cone avoidance, surface gradients, guidepost cells, and
      chemotropism. Analysis of the molecular basis for these guidance mechanisms show
      that the molecules involved often belong to distinct multigene families and that
      they can provide both short- and long-range attractive as well as repulsive cues.
      Many of these molecules have a modular structure that is made up of different
      tandemly arranged domains that allow for multiple functional interactions with a
      range of other molecules. This allows the same molecule to be multifunctional,
      for example, by attracting certain neurons while repelling others. This review is
      an overview of the molecular structure, as it relates to function and mechanisms
      of action of some of the major gene families thought to be mediating specific
      axonal guidance and pathway formation.

PMID- 9034718
TI  - Gene regulatory mechanisms operative on hematopoietic cells: proliferation,
      differentiation, and neoplasia.
AB  - Blood cell formation is a highly regulated process that relies on the ability of
      a limited number of hematopoietic stem cells to undergo self-renewal or
      commitment into lineage-restricted progenitors. The daily maintenance of
      circulating blood cells and the adaptation to abnormal circumstances that alter
      the tissue homeostasis is ensured by the expansion and the differentiation of
      committed progenitors. Neoplastic transformation of hematopoietic cells is an
      extreme manifestation of the inability to coordinate proliferation and
      differentiation in the progenitor cell pool. Hematopoiesis-specific transcription
      factors play a central role in these processes both as normal regulators or, when
      aberrantly activated, as the pathogenetic agents in disease initiation and
      progression.

PMID- 9034719
TI  - Mammalian cell DNA replication.
AB  - The precise mechanisms involved in the regulation of the mammalian cell DNA
      synthesizing machinery are poorly understood. In vitro DNA replication systems,
      in particular the employment of the simian virus 40 (SV40)-based cell-free DNA
      replication system, has identified several mammalian enzymes and proteins
      required for DNA synthesis. Although these proteins have been identified as
      playing a role in DNA replication, their functional organization allowing for the
      efficient replication of DNA has not been well defined. This review describes the
      proteins that have currently been defined as having a role in mammalian DNA
      replication and their proposed mechanisms of action. How these proteins may
      organize themselves to form multiprotein complexes, or larger DNA replication
      factories, allowing for efficient chromosomal DNA synthesis is discussed. In
      addition, the cell cycle regulation of mammalian DNA synthesis and the current
      status concerning mammalian DNA replication origins is described.

PMID- 9034720
TI  - Transcriptional control of matrix metalloproteinases and the tissue inhibitors of
      matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) are enzymes with important roles in a variety of
      normal physiological processes; these same enzymes are also operative in a range
      of pathologies. The proteins known as the tissue inhibitors of matrix
      metalloproteinases (TIMPs) act to limit the enzymatic function of the MMPs. MMPs
      and TIMPs can be divided into two groups with respect to gene expression: the
      majority exhibit inducible expression and a small number are produced
      constitutively or are expressed at very low levels and are not inducible. Among
      the agents that induce MMP and TIMP production are the inflammatory cytokines TNF
      alpha and IL1 beta. A marked cell type specificity is a hallmark of both MMP and
      TIMP gene expression (i.e., a limited number of cell types can be induced to make
      these proteins). An analysis of the control elements in the promoter regions of
      these proteins reveals a correlation between the presence of both AP-1 and Ets
      binding sites and inducible expression. The chromosomal locations of most of the
      MMPs and TIMPs have been verified; these data will provide the basis for
      investigations into possible correlations between mutations in these genes and
      disease states.

PMID- 9034721
TI  - Gene regulation associated with apoptosis.
AB  - Apoptosis, one of the best-studied forms of programmed cell death processes,
      plays an important role during the development and life-cycle of most
      multicellular organisms. The mechanisms underlying the initiation and
      manifestation of apoptotic cell death are the focus of the most recent cell death
      research. Generally, it is believed that cells are eliminated via a highly
      ordered and controlled program. This program might consist of the successive
      activation of unique apoptosis-specific genes, which are solely involved in the
      regulation of the programmed cell death. However, more and more evidence is
      accumulating that novel genes are not activated or induced during apoptosis, but
      rather many well-known genes previously described for their roles in processes
      such as proliferation and differentiation and belonging, for example, to the
      protein families of immediate-early genes and transcription factors become
      activated. The death-specific feature is achieved thereby by the extent,
      combination, and specific timing of gene expression. The involvement of the three
      different transcription factors glucocorticoid receptor (GR), nur77, and
      activator protein 1 (AP-1) in such a scenario is the focus of this review.

PMID- 9034722
TI  - Functions of IL-4 and control of its expression.
AB  - IL-4 has been called the "prototypic immunoregulatory cytokine." Like many
      cytokines, it can affect a variety of target cells in multiple ways. IL-4 has an
      important role in regulating antibody production, hematopoiesis and inflammation,
      and the development of effector T-cell responses. It is produced only by a subset
      of activated hematopoietic cells, including T cells and Fc epsilon R1+ mast cells
      and basophils. Based on the different tissue distribution and access to distinct
      target cells, IL-4 derived from T and Fc epsilon R1+ cells may have quite
      different effects on these immunological processes. In view of this, as well as
      the clear correlation of aberrant expression with disease, it is of interest to
      understand the signals that regulate IL-4 expression in a cell-specific manner.
      Recently, progress has been made in defining the T-cell- and Fc epsilon R1
      receptor-mediated signals that stimulate IL-4 gene expression. These studies have
      demonstrated that there are common and cell-specific signaling pathways that
      regulate production of this cytokine. In this review, we summarize the activities
      of IL-4 defined both in vitro and in vivo and compare the signals leading to IL-4
      expression in cells of both T- and mast-cell lineage.

PMID- 9034723
TI  - Autoimmune pathogenesis of multiple sclerosis: role of autoreactive T lymphocytes
      and new immunotherapeutic strategies.
AB  - Accumulating evidence indicates that multiple sclerosis (MS) is an autoimmune
      disease mediated by autoreactive T lymphocytes with specificity for myelin
      antigens. Initially, the evidence to support this hypothesis was based mainly on
      experiments performed in experimental allergic encephalomyelitis (EAE), the
      animal model of MS. In this model it was demonstrated that T cells reactive to
      several myelin antigens are encephalitogenic. Many recent immunological and
      immunohistochemical studies in MS have yielded further data to support this view.
      For instance, it was demonstrated that activated myelin basic protein (MBP) and
      proteolipid protein (PLP)-specific T cells accumulate in the central nervous
      system (CNS), and that clonally expanded MBP-specific T cells persist for several
      years in the blood of patients with MS. Furthermore, T cells with specificity for
      MBP were identified in the brain lesions of the patients. It is not yet clear how
      these autoreactive T cells are activated in the periphery, but several studies
      have suggested that viral antigens mimicking the myelin epitopes, or
      superantigens may be involved. Furthermore, we and others have provided evidence
      showing that the regulatory mechanisms that control autoreactive T cells in
      healthy subjects are potentially defective in MS patients. In addition to myelin
      reactive T cells, B cells producing myelin-specific antibodies and gamma delta T
      cells may also play an important role in the autoimmune cascade. Based on the
      recent insights in the disease mechanisms, new experimental therapies were
      developed to target specifically the pathogenic lymphocytes in MS. Some therapies
      yielded encouraging data in pilot studies, whereas phase III trials of other
      drugs showed beneficial effects on the disease course. In this article, we
      overview the most recent data on the role of autoreactive lymphocytes in the
      pathogenesis of the disease, and discuss some of the recently developed
      immunotherapeutical strategies in MS.

PMID- 9034724
TI  - Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator
      within the immune system.
AB  - Originally described as a T lymphocyte-derived factor that inhibited the random
      migration of macrophages, the protein known as macrophage migration inhibitory
      factor (MIF) was an enigmatic cytokine for almost 3 decades. In recent years, the
      discovery of MIF as a product of the anterior pituitary gland and the cloning and
      expression of bioactive, recombinant MIF protein have led to the definition of
      its critical biological role in vivo. MIF has the unique property of being
      released from macrophages and T lymphocytes that have been stimulated by
      glucocorticoids. Once released, MIF overcomes the inhibitory effects of
      glucocorticoids on TNF alpha, IL-1 beta, IL-6, and IL-8 production by LPS
      stimulated monocytes in vitro and suppresses the protective effects of steroids
      against lethal endotoxemia in vivo. MIF also antagonizes glucocorticoid
      inhibition of T-cell proliferation in vitro by restoring IL-2 and IFN-gamma
      production. This observation has identified a pivotal role for MIF within the
      immune system and fills an important gap in our understanding of the control of
      inflammatory and immune responses. Glucocorticoids have long been considered to
      be an integral component of the stress response to infection or tissue invasion
      and serve to modulate inflammatory and immune responses. MIF is the first
      mediator to be identified that can counter-regulate the inhibitory effects of
      glucocorticoids and thus plays a critical role in the host control of
      inflammation and immunity.

PMID- 9034725
TI  - Accessory molecule and costimulation requirements for CD4 T cell response.
AB  - T cell activation is brought about by recognition of peptide/MHC complexes on an
      antigen-presenting cell (APC) by the T cell receptor (TCR). However, in general
      this appears to be insufficient for the full development of T cell responses and
      therefore additional signals are required, provided by ligation of counter
      receptors on the T cell by APC accessory molecules. Although many studies have
      suggested that B7 molecules (CD80/CD86) binding to CD28 induce this second
      signal, it is now evident that any one of a number of molecules may provide
      accessory function and that efficient response is only generated following
      multiple interactions. It has also become clear that T cells exist in varying
      states of activation or differentiation, and that requirements for accessory
      molecules and costimuli are not always equivalent. This review covers much of the
      recent data regarding accessory molecule regulation of T cell responses. A
      modified version of the two signal model is presented, suggesting that the major
      function of accessory molecules during the initial stages of activation is to
      augment the ability to signal through the TCR, and that the primary role of
      costimulatory signals is to allow IL-2 secretion and growth. The requirement for
      multiple accessory molecules interactions is discussed in relation to activation
      of naive T cells and how such interactions are less critical at the memory and
      effector stages. Finally, this new information is related to how T cells interact
      with varying APC and how these interactions may modulate T cell response.

PMID- 9034727
TI  - "Workload limits" and CLIA 88 in the 1990's: how much is too much? Or too little?

PMID- 9034728
TI  - Atypical squamous cells of undetermined significance: correlative histologic and
      follow-up studies from an academic medical center.
AB  - The diagnosis of ASCUS (atypical squamous cells of undetermined significance) was
      introduced in the 1988 Bethesda System for reporting cervical/vaginal cytologic
      findings. Outcome and appropriate management of patients with this diagnosis is
      not presently established. Criteria defining ASCUS are nuclear enlargement (2.5
      3.0 times normal intermediate cell nucleus), mild nuclear hyperchromasia, smooth
      nuclear outlines with mild variation in nuclear size and shape, or else two, but
      not all three, cytologic criteria for human papilloma virus (HPV) cytopathic
      effect. All 668 cases reported as ASCUS from February 1992-December 1993 from our
      cytology laboratory were reviewed. These ASCUS cases represented 4.5% of all
      gynecologic cases diagnosed in that same time period. Of these, 284 (41%) had a
      subsequent colposcopic biopsy and/or endocervical curettage. The biopsied cases
      included 101 (36%) with condylomata, 38 (13%) with cervical intraepithelial
      neoplasia (CIN) I, 17 (6%) with CIN II, and 9 (3%) with CIN III. No cases of
      carcinoma were detected. Of patients with a cytologic diagnosis of ASCUS and
      subsequent cervical biopsy, 49% had low-grade cervical intraepithelial neoplasia
      (LGSIL), either condyloma or CIN I. Nine percent had high-grade cervical
      intraepithelial neoplasia, either CIN II or CIN III. These findings indicate that
      ASCUS defines cytologically a group of patients who may have either a concurrent
      or subsequent development of a squamous intraepithelial lesion (SIL). This forms
      a high-risk group. The management of cases with a cytologic diagnosis of ASCUS
      should be at least as aggressive as that of LGSIL.

PMID- 9034729
TI  - Hepatocellular carcinoma: needle biopsy findings in 74 cases.
AB  - Needle aspiration specimens from 74 cases of hepatocellular carcinoma (HCC)
      diagnosed between January 1986 and December 1992 were reviewed and compared with
      57 other lesions. The most specific cytologic findings for HCC included
      capillaries separating tumor cells (34%), bile associated with malignant cells
      (19%), and endothelial cells lining clusters of neoplastic cells (18%). Less
      specific findings included polygonal cells with central nuclei resembling normal
      hepatocytes and intranuclear inclusions. Tissue core fragments available in 53
      cases of HCC disclosed that a weak keratin (AE1/AE3) stain (75% of HCC), a
      canalicular pattern of polyclonal carcinoembryonic antigen (54%), and a positive
      alpha-fetoprotein stain (58%) are diagnostic of HCC. All HCCs were negative for
      monoclonal carcinoembryonic antigen. In situ hybridization for albumin mRNA was
      positive in 27 of 33 cases of HCC. The diagnosis of HCC by needle biopsy should
      include cytologic findings and the appropriate immunohistochemical profile, along
      with detection of albumin mRNA by in situ hybridization.

PMID- 9034730
TI  - Fine-needle aspiration cytodiagnosis of recurrent carcinoma of the breast in
      operative scars.
AB  - Recurrence of carcinoma in scars following surgical treatment of breast carcinoma
      is a frequent problem. An early diagnosis of recurrent lesions is essential to
      enable timely management. In this study, the role of fine-needle aspiration
      cytology (FNAC) in the diagnosis of scar lesions was evaluated in 156 women seen
      over a period of 12 1/2 yr. Ninety-eight of these on FNAC showed features of a
      recurrent carcinoma, and in six samples, the FNAC showed suspicious features. In
      all the six suspicious cases, a subsequent biopsy confirmed a recurrent breast
      carcinoma. The remaining 52 cases on repeated FNAC were diagnosed as benign, and
      this was confirmed on a subsequent biopsy. The sensitivity, specificity, and
      predictive value for cytologic findings were 94.2, 100, and 100%, respectively.
      It was concluded that FNAC clearly has a role as a first line of investigation
      for distinguishing between recurrent malignant and benign lesions in scars in
      women which have been surgically treated for a breast carcinoma.

PMID- 9034731
TI  - Percutaneous needle biopsy diagnosis of benign neurogenic neoplasms.
AB  - Preoperative diagnosis of benign neurogenic neoplasms (BNNs) provides useful
      information in guiding management. To assess the effectiveness of fine-needle
      aspiration (FNA) and needle core biopsy (NCB) in diagnosing schwannomas and
      neurofibromas, 40 percutaneous biopsies interpreted as BNNs or obtained from
      lesions subsequently shown by excision to be BNNs were reviewed. The 13 aspirates
      diagnostic of BNN revealed spindle cells arranged haphazardly in irregular tissue
      fragments and in parallel as elongated ropy fascicles, with a myxoid to
      fibrillary background. The nuclei were buckled, often with intranuclear
      cytoplasmic inclusions. Four lesions showed nuclear pleomorphism without mitoses.
      Of 19 schwannomas evaluated by FNA, four (21%) were diagnosed as schwannomas and
      seven (37%) as BNNs. Ten neurofibromas were aspirated, revealing two (20%) BNNs.
      Of seven nondiagnostic FNAs accompanied by NCB, three (43%) indicated a BNN. The
      sensitivities of FNA, NCB, and both modalities in diagnosing BNNs were 43,60, and
      71%, respectively. For the 16 FNAs showing features of BNNs, subsequent excisions
      revealed 11 schwannomas, two neurofibromas, one neurogenic sarcoma, one
      fibromyxoid neoplasm of uncertain malignant potential, and one unclassified low
      grade myxoid sarcoma. FNA can be effective in diagnosing BNNs. If collagenous or
      myxoid lesions yield paucicellular nondiagnostic aspirates, NCB is helpful.
      Lowgrade sarcoma and neurofibromatous areas of neurogenic sarcoma may be
      misinterpreted as BNNs by percutaneous biopsy. BNNs may show nuclear pleomorphism
      without mitotic activity, and should not be mistaken for sarcoma.

PMID- 9034732
TI  - Aspergillus in cytology specimens: a review of 45 specimens from 36 patients.
AB  - OBJECTIVE: To assess the clinical significance associated with the identification
      of fungal elements consistent with Aspergillus in cytology specimens. MATERIALS
      AND METHODS: For all cytology specimens with reported fungal elements consistent
      with Aspergillus, reported over a 9 yr and 8 mo period at The Cleveland Clinic
      Foundation, the patient's medical charts were reviewed with particular attention
      to underlying disease, presentation, treatment, and clinical course. Cytology
      results were compared with available microbiologic cultures and tissue specimens
      in all of the patients. RESULTS: Forty-five cytology specimens with Aspergillus
      fungal forms, from 36 patients, were identified. Twenty-six patients had
      concurrent specimens sent for culture in whom II grew Aspergillus species (10
      Aspergillus fumigatus), eight grew organisms other than Aspergillus, and seven
      were no growth. A total of 16 patients (44%) were treated with antifungal
      treatment (Amphotericin B). Treatment with Amphotericin B was significantly
      associated with a concurrent growth of Aspergillus species (9/11 patients with
      Aspergillus culture positive vs. 7/25 patients without a positive culture for
      Aspergillus, P value = 0.004 (ODDS ratio = 11, 95% confidence interval:#1.6-104,
      2-tailed Fisher exact test.) CONCLUSIONS: The presence of fungal forms consistent
      with Aspergillus in cytology specimens is neither specific nor sensitive for
      significant infection due to Aspergillus. Treatment with Amphotericin B is more
      likely to be instituted when a concurrent clinical specimen grows Aspergillus
      species in culture.

PMID- 9034733
TI  - Fine-needle aspiration biopsy in fungal infections.
AB  - To evaluate the role of fine-needle aspiration biopsy (FNAB) in diagnosis of
      fungal infections, a retrospective analysis of 26 cases of fungal infection is
      described. The spectrum of various fungi encountered on cytologic microscopy of
      aspirated material and fungal culture was as follows: Aspergillus sp (16 cases),
      Cryptococcus neoformans (six cases), Mucorales (one case), Candida sp (one case),
      Phialophora parasiticus (one case), Sporothrix schenkii and Cladosporium sp (the
      last two isolated from a single case). In majority (71%) of cases, fungal
      infection was not clinically suspected but was picked up on cytologic material in
      all the cases. An accurate diagnosis based on morphology could be made in 21
      cases (80%). Predisposing factor was found in three patients, two of them had
      diabetes mellitus and one was on immunosuppression. HIV serology was negative in
      seven cases tested. Commonest tissue reaction (75%) was foreign body giant cells
      with foamy macrophages and variable amount of necrosis. Although FNAB is helpful
      in the rapid diagnosis of fungal infections, culture is essential for more
      accurate identification.

PMID- 9034734
TI  - Cytologic diagnosis of syphilitic pleuritis: a case report.
AB  - We report on a case of a 68-yr-old man with secondary syphilis diagnosed by
      biopsy of skin lesions, who concomitantly suffered from left lower lobe pneumonia
      with associated pleuritis. Cytologic examination of the pleural fluid was
      diagnostic of syphilis, not only by the characteristic cytomorphology but also by
      demonstration of spirochetes by the May-Grunwald-Giemsa (MGG) and Steiner
      staining methods. This suggests that the pneumonia was also syphilitic. The
      patient was seropositive for HIV-I, but this probably did not contribute to the
      thoracic manifestations of syphilis, as there was no evidence of immunodeficiency
      by the CD4/CD8 T lymphocyte count. This is the second reported demonstration of
      Treponema pallidum in a pleural fluid, and the first diagnosed by cytopathologic
      examination.

PMID- 9034735
TI  - Follicular carcinoma arising in ectopic thyroid tissue: case report with fine
      needle aspiration findings.
AB  - A 32-yr-old woman was found to have a 1 x 2 cm mass in the soft tissue of the
      neck 1 cm lateral to the left lobe of the thyroid gland. A fine-needle aspiration
      biopsy showed a follicular neoplasm. The excised mass showed a follicular
      carcinoma arising in lateral ectopic thyroid tissue. Subsequent excision of the
      thyroid gland and pathological examination showed no primary carcinoma in the
      gland. This report illustrates a case of primary follicular carcinoma arising in
      a lateral ectopic thyroid tissue in the neck.

PMID- 9034736
TI  - Embryonal adenoma of the kidney: a report of two cases.
AB  - Embryonal (metanephric) adenoma of the kidney, like Wilms' tumor, exhibits small
      monomorphic, blue cells arranged as vague, tubular rosettes. Unlike Wilms' tumor,
      which requires chemotherapy or multi-modality therapy for optimal management, the
      available evidence indicates that embryonal adenoma is most likely cured by
      simple enucleation or nephrectomy. Two women, age 54 (Case 1) and 78 (Case 2),
      respectively, underwent needle biopsy for a radiologically well circumscribed
      renal lesion with associated hematuria. The cellular smears contained vague
      rosette-like arrangement of small, blue cells with scant cytoplasm and evenly
      distributed, fine, nuclear chromatin. In cell blocks, these cells were arranged
      as compact, primitive, tubular rosettes or rare, moresolid clusters. Assuming
      that the absence of undifferentiated blastema and primitive glomeruli represented
      a sampling error, a diagnosis suggesting of Wilms' tumor was made in Case 1. At
      nephrectomy, despite extensive sampling, the typical triphasic Wilms' morphology
      and anaplastic or necrotic areas were not seen. In the presence of architectural
      monotony, the diagnosis in Case 1 was amended to embryonal adenoma. Case 2 was
      cytologically diagnosed as embryonal adenoma of the kidney and is being followed
      conservatively. In our opinion, the presence of monotypic architecture at
      cytology/histology is very helpful in differentiating renal embryonal
      (metanephric) adenoma from Wilms' tumor.

PMID- 9034737
TI  - Fine-needle aspiration of pigmented villonodular synovitis of the
      temporomandibular joint masquerading as a primary parotid gland lesion.
AB  - The fine-needle aspiration findings in a case of pigmented villonodular synovitis
      of the temporomandibular joint are presented. The characteristic cytomorphologic
      and clinical features of this uncommon, benign fibrohistiocytic lesion are
      discussed. In addition, due to the initial clinical impression of a primary
      parotid gland lesion, the differential diagnosis for the cytomorphologic features
      observed (histiocytoid cells admixed with osteoclast-like giant cells) are
      discussed within the context of a primary salivary gland mass.

PMID- 9034738
TI  - Nodular hematopoiesis of the liver diagnosed by fine-needle aspiration cytology.
AB  - A case of tumor-like extramedullary hematopoiesis (EMH) of the liver diagnosed by
      fine-needle aspiration cytology guided by computer tomography (CT) is reported.
      The initial clinical diagnosis was metastatic carcinoma from an adrenal gland
      primary. Five other cases of tumor-like EMH diagnosed by FNA have been presented
      in the literature. In two of the cases, the primary clinical diagnosis was
      metastatic tumor. The most common location for tumor-like EMH is paravertebral
      and intrathoracic. Three such cases of paravertebral tumor-like EMH have been
      diagnosed by FNA. Nodular EMH can be found rarely in other organs as in the
      liver.

PMID- 9034739
TI  - Biliary stricture due to hepatocellular carcinoma: diagnosis by bile duct
      brushing cytology.
AB  - Bile duct brushing cytology is a useful technique in the diagnosis of malignant
      biliary strictures. Adenocarcinoma is the usual type of carcinoma diagnosed in
      these brushing specimens. This report details the bile duct brushing cytology
      findings in an unusual case of hepatocellular carcinoma which presented with
      obstructive jaundice due to invasion of the biliary tract. A striking feature of
      the brushing was the prominent capillary vascular pattern associated with the
      tumor cells. This is a cytologic feature which has been noted in fine-needle
      aspirates of hepatocellular carcinoma as well, and is distinct from the expected
      findings in adenocarcinoma.

PMID- 9034740
TI  - Diagnostic significance and possible pitfalls of nuclear grooves in extrathyroid
      cytology.
AB  - The diagnostic significance of grooved nuclei in the cytology of extrathyroid
      lesions is not well-described in the literature. Isolated cases of metastatic
      adult granulosa cell tumor, reactive mesothelial hyperplasia, Langerhans' cell
      histiocytosis, recurrent renal cell carcinoma, and round cell liposarcoma were
      reviewed, and their cytologic features were discussed. While nuclear grooving can
      be present to a different extent in all these conditions, the significance of
      this feature in diagnostic cytology varies. The integration of clinical
      information, radiologic findings, different morphologic features, and
      immunohistochemistry is necessary before a final conclusion is reached.

PMID- 9034741
TI  - Chondroblastoma of bone: use of fine-needle aspiration biopsy and potential
      diagnostic pitfalls.
AB  - Chondroblastoma of bone is a well-characterized entity. When the radiographic
      features are classic and the lesion is present in typical locations (i.e.,
      epiphysis of a long bone), the diagnosis is often easily established by fine
      needle aspiration biopsy and/or surgical curettage. Tumors in unusual locations,
      in older patients, or when complicated by aneurysmal bone cysts may pose more
      diagnostic difficulty. We report four examples (three primary and one-recurrent)
      of chondroblastoma of bone diagnosed by fine-needle aspiration biopsy. All
      patients were men, ranging from 18 to 28 yr of age. Sites of involvement included
      the acromion process of the scapula, left humerus, right ischium, and left distal
      femur. Three of the tumors were diagnosed as chondroblastoma on fine-needle
      aspiration cytology; the fourth case, involving the scapula, consisted mostly of
      a large aneurysmal bone cyst and remained unrecognized until surgical curettage
      was performed. Typical-appearing chondroblasts were present in three of the
      cases; osteoclast-type giant cells were observed in all four cases. Matrix
      material consistent with chondroid was also identified in all cases. We believe
      that in the absence of inflammatory cells, the presence of classic-appearing
      chondroblasts, even without chondroid matrix, is sufficient for a diagnosis of
      chondroblastoma of bone.

PMID- 9034742
TI  - Is it feasible to diagnose germ-cell tumors by fine-needle aspiration biopsy?
AB  - Fine needle aspiration biopsy is an extremely useful procedure for the diagnosis
      of germ cell tumors. Most of the subtypes can be easily recognized and
      differentiated from other subtypes. For difficult cases clinical pathologic
      correlation may be extremely helpful in establishing a precise diagnosis. Mixed
      germ cell tumors may cause some difficulty if one of the components is
      predominant. Immunohistochemistry may also play an important role in arriving at
      a definitive diagnosis.

PMID- 9034743
TI  - Ciliated cell adenocarcinoma of the endometrium diagnosed by endometrial brush
      cytology and confirmed by hysterectomy: a case report detailing a highly
      efficient cytology collection and processing technique.
AB  - A case of ciliated endometrioid adenocarcinoma of the endometrium, diagnosed by
      endometrial brush cytology and confirmed by histology, is reported. Features are
      those of outspoken endometrial adenocarcinoma presenting in a postmenopausal
      woman with abnormal uterine bleeding. Distinctive characteristics include
      ciliated neoplastic cells, intracytoplasmic ciliary cysts, complex epithelial
      stratification, and muscular invasion by malignant ciliated cells in the matched
      hysterectomy specimen. This report illustrates the merit of linking an easy-to
      use liquid fixative with brush-sampling of the endometrium.

PMID- 9034744
TI  - Candida-related changes and ASCUS: a potential trap!
AB  - Detection of potential pitfalls for the ASCUS interpretation is essential for
      appropriate patient management. Between 1991-1994, 50 cervicovaginal specimens
      with Candida spp. were submitted for pathologists' review because of a possible
      ASCUS diagnosis. None had been preceded by abnormal smears, and all were followed
      by one or more benign smears and/or biopsy. Candida-associated changes included
      nuclear enlargement with focal hyperchromasia and cytoplasmic changes of
      orangeophilia, vacuoles, and perinuclear rings. Initially, 16 cases had been
      interpreted as ASCUS and 34 as benign. Upon review, utilizing strict Bethesda
      System criteria for ASCUS and awareness of Candida-associated changes, 10 of the
      16 ASCUS cases were reclassified as benign. Knowledge of Candida-associated
      changes which may mimic ASCUS can prevent overuse of the ASCUS term, providing
      optimal, cost-effective management.

PMID- 9034745
TI  - Intralaboratory quality assurance in cervical/vaginal cytology: evaluation of
      intercytologist diagnostic reproducibility.
AB  - Diagnostic reproducibility and accuracy in evaluating cervical/vaginal smears
      were the focus of this study concerning intralaboratory quality control. A set of
      120 cytological samples was evaluated by 15 cytopathologists whose experience
      ranged from 3-29 yr. The study report form was based on the 1988 Bethesda System.
      Intercytologist reproducibility (with respect to sample adequacy, epithelial cell
      abnormalities, and presence of cellular changes associated with HPV, Human
      Papilloma virus) was evaluated using the Kappa statistic. Poor reproducibility in
      defining sample adequacy was observed (K = 0.24). The agreement on epithelial
      cell abnormality definition was good (K = 0.64); the lowest reproducibility was
      observed for High-grade squamous intraepithelial lesion/cervical intraepithelial
      neoplasia HSIL/CIN II (specific K = 0.37) and Atypical cells of undetermined
      significance ACUS (specific K = 0.44). The agreement in detecting cellular
      changes associated with HPV was fair (K = 0.49). Diagnostic accuracy for
      epithelial cell abnormalities, assessed by comparison with a consensus reference
      diagnosis, was good (K = 0.74).

PMID- 9034746
TI  - Unexpected diagnosis of hydatid cyst by fine-needle biopsy (FNB)

PMID- 9034747
TI  - Fine needle aspiration of metastatic malignant schwannoma to the thyroid gland.

PMID- 9034748
TI  - Pap smears of patients on tamoxifen.

PMID- 9034749
TI  - Automated rescreening of Papanicolaou smears.

PMID- 9034750
TI  - Endothelial function. General considerations.
AB  - The endothelium is involved in both the physiological regulation of vascular tone
      and the structural transformation of the vessel under pathological conditions.
      Under physiological conditions, endothelial cells continuously secrete nitric
      oxide (NO), which relaxes smooth muscle cells and ensures vessel patency. Damaged
      or excessively activated endothelial cells can also secrete vasoconstrictor
      factors, the best known of which is endothelin-1 (ET-1), as well as factors that
      affect the differentiation and growth of vascular smooth muscle cells. How
      endothelial cell damage contributes, under pathological conditions, to vascular
      disease can best be illustrated in patients with diabetes mellitus, in whom there
      are pronounced changes in endothelial cell structure and function. Endothelial
      cells also interact with cells in the bloodstream, ET-1 and other factors are
      released from endothelial cells into the bloodstream, where their chemotactic
      action can induce leucocytes and platelets to migrate to the endothelial wall.
      Endothelial cells induce adhesion by expression of specific surface adhesion
      molecules (selectins, integrins and a supergene family of immunoglobulins) that
      can interact with ligands on the leucocytes and platelets. The expression of
      adhesion molecules is increased in endothelial cells chronically damaged by risk
      factors for atherosclerosis. The disturbed permeability of the endothelial layer
      in patients with diabetes mellitus and/or hyperlipidaemia leads to an increased
      influx of substances from the circulation into the vessel wall. In addition,
      endothelial cell dysfunction can lead to accelerated intravessel blood
      coagulation. It is evident that the endothelium plays a central role in many of
      the early pathophysiological processes involved in atherosclerosis. It is
      therefore important to investigate the effects of antiatherosclerotic therapy on
      endothelial cell function and cell-to-cell interactions. Until recently, little
      was known about the direct effects of calcium antagonists on endothelial cell
      function. Recent studies, including two clinical studies, indicate that calcium
      antagonists primarily affect interactions of endothelial cells, smooth muscle
      cells, monocytes and platelets, which play a central role in the early phases of
      the development of atherosclerosis, whereas the protective effect of these agents
      on the vascular system appears to be low at later stages.

PMID- 9034751
TI  - Endothelial function and the kidney. An emerging target for cardiovascular
      therapy.
AB  - Endothelial dysfunction is emerging as an important factor in the early
      development of acute and chronic renal disease. Drugs aimed specifically at
      rectifying this aberration are being developed, although other established agents
      such as calcium antagonists, angiotensin converting enzyme (ACE) inhibitors and
      HMG CoA reductase inhibitors also have beneficial effects in this setting.
      Calcium antagonists are particularly effective at ameliorating acute renal
      ischaemia associated with endothelial dysfunction. Combination therapy with a
      calcium antagonist and an ACE inhibitor might optimise the beneficial effects of
      calcium channel blockade on the sequelae of endothelial dysfunction in chronic
      renal failure.

PMID- 9034752
TI  - Coronary endothelial function in health and disease.
AB  - The endothelium participates in the control of coronary vascular tone and growth
      through the release of vasodilating and growth-inhibiting factors such as nitric
      oxide (NO) and C-type natriuretic peptide (CNP), and vasoconstricting and growth
      promoting substances such as endothelin-1 (ET-1). Abnormalities in NO and/or CNP
      generation or actions have been demonstrated in various cardiovascular
      pathophysiological states, specifically atherosclerosis, congestive heart
      failure, hypertension and hypercholesterolaemia. Moreover, an increase in plasma
      ET-1 levels has also been reported in these disease states. When these
      observations are considered together, these states may be characterised by an
      attenuated release or action of NO and/or CNP, together with an augmented release
      of ET-1. Thus, an imbalance between these opposing factors may contribute to the
      alteration in vascular tone and the vascular remodelling characteristics of
      cardiovascular disease. The following article summarises the present knowledge of
      endothelial control of the coronary circulation and derangements associated with
      coronary endothelial dysfunction.

PMID- 9034753
TI  - Endothelial dysfunction and hypertension.
AB  - Vascular endothelial cells play a key role in cardiovascular regulation by
      producing a number of potent vasoactive agents, including the vasodilator
      molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET)-1. A
      dysfunction of the vascular endothelium has been implicated in the
      pathophysiology of a number of cardiovascular diseases, important among which is
      essential hypertension. Impairment of NO synthesis, or increased inactivation of
      NO by superoxide radicals, may account for the increased peripheral vascular tone
      associated with hypertension, as well as contribute to the clinical consequences
      of this condition, which include vascular hypertrophy, increased platelet and
      monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and
      stroke. Similarly, increased ET-1 synthesis, or increased smooth muscle
      sensitivity to ET-1, could account for many of the features of hypertension,
      including increased peripheral vascular tone and vascular hypertrophy. Modulation
      of endothelial function is, therefore, an attractive therapeutic option in the
      treatment of hypertension. Calcium antagonists have been shown to enhance the
      effects of NO, and inhibit those of ET-1, on vascular smooth muscle cells. In
      addition, calcium antagonists have antiatherogenic and antioxidant properties and
      could, therefore, prove to be useful therapeutic agents in preventing some of the
      important complications of hypertension. The long term effects on cardiovascular
      morbidity and mortality of the long-acting nifedipine gastrointestinal
      therapeutic system (nifedipine GITS) used in the treatment of essential
      hypertension are currently being investigated in the first multinational outcome
      study (INSIGHT) of an antihypertensive agent since the major studies of beta
      adrenoceptor blockers or thiazide diuretics. The results of this study are
      awaited with considerable interest.

PMID- 9034754
TI  - The antiviral, antitumoural xanthate D609 is a competitive inhibitor of
      phosphatidylcholine-specific phospholipase C.
AB  - The effect of the antiviral, antitumoural xanthate D609 on the activity of
      phospholipase A2, C (PC- and Pi-specific) and D was investigated. D609 is the
      first model substance of a new concept of antiviral therapy that interferes with
      cellular regulation mechanisms, rather than with virus coded enzymes. Exclusively
      phosphatidylcholine (PC) specific phospholipase C (PC-PLC) was found to be
      inhibited in a dose-dependent manner. Enzyme activity was determined either as
      the rate of acid release from PC or as the rate of phosphorylcholine production
      form 3H labelled PC. Lineweaver-Burk plots revealed D609 as a competitive
      inhibitor of PC-PLC with a Ki of 6.4 microM. In addition, D609 competitively
      inhibited PC-PLC mediated cleavage of P-nitrophenylphosphorylcholine (p-NPP), a
      pseudo-substrate of PC-PLC with a Ki of 8.8 microM. These data suggest that D609
      competes with the phosphorylcholine residue of PC for binding to PC-PLC.

PMID- 9034755
TI  - Verapamil increases the bacteriostatic and bactericidal effects of adriamycin on
      Escherichia coli.
AB  - The purpose of this study was to evaluate the effect of verapamil on adriamycin
      resistant and -sensitive Escherichia coli bacterial strains. Two E. coli strains:
      B-SR9 and K12-KL16 were incubated with adriamycin in various concentrations in
      the presence or absence of verapamil. Growth and killing rates were measured
      using optical densities and colonogenic assays. Transmembrane transport capacity
      was evaluated by measuring radioactively labelled leucine uptake and
      intracellular potassium concentrations. While adriamycin (ADR) showed both
      bacteriostatic and bactericidal effects upon the two bacterial strains, the K12
      strain was significantly more resistant to the drug than its peer. Subtoxic
      concentrations of verapamil augmented these effects in both strains. Verapamil
      affected bacterial transmembrane transport activity and caused potassium leakage
      through the cell membrane. Simultaneous exposure to adriamycin and verapamil
      resulted in rapid, massive damage to membrane functions, indicating accelerated
      killing rate. The authors concluded that verapamil acts as a potentiator of
      adriamycin's cytotoxicity in E. coli bacteria in a manner similar to that in
      multidrug resistant mammalian tumour cells. This observation suggests that the
      mechanisms of resistance to the drug may be similar in both species.

PMID- 9034756
TI  - In vitro susceptibility of 115 isolates of Candida to amphotericin B, fluconazole
      and itraconazole.
AB  - Opportunistic fungal infections are an increasingly important cause of morbidity
      and mortality particularly due to Candida species (1). There is also an increase
      of candidosis especially ascribed to acquired or induced immunodeficiency
      syndromes or in the event of long-term antibiotic, immuno-suppressor or cytotoxic
      therapies. Consequently there has been an increase in the use of systemic
      antifungal agents responsible for the emergence of new opportunistic fungi (2)
      and resistant species (3, 4). Oropharyngeal candidiasis caused by various species
      of Candida is one of the most common opportunistic infections in AIDS. In recent
      years there has been an increasing number of yeast isolates resistant to
      fluconazole (4, 5) or to amphotericin B (6). The aim of the present study was to
      examine the susceptibility in vitro of itraconazole, a newly introduced
      antifungal agent in the local or systemic therapy of oropharyngeal candidiosis,
      vs well-known agents such as amphotericin B and fluconazole, against various
      Candida clinical isolates. The present results, in agreement with other studies,
      show strong in vitro activity of itraconazole against Candida spp. and
      particularly against less susceptible species C. glabrata, C. tropicalis or C.
      krusei.

PMID- 9034757
TI  - The protective effect of aqueous propolis extract on isolated rat hepatocytes
      against carbon tetrachloride toxicity.
AB  - The protective effect of honeybee aqueous propolis extract (APE) against the
      hepatotoxicity of carbon tetrachloride was investigated using isolated liver-cell
      suspensions as the experimental model. Various concentrations of the extract were
      preincubated with the hepatocyte suspensions for 30 min before being subjected to
      the hepatotoxin for a further 30 min. The hepatocyte toxicity was assessed using
      three parameters, namely, the release of lactate dehydrogenase, the formation of
      lipid peroxides and the depletion of intracellular reduced glutathione. It was
      found that a dose-related protection against the induced cell injury was
      conferred by APE as evidenced by its inhibitory influence on the changes induced
      by CCl4 on the measured parameters. The hepatocyte protective effect of APE is
      probably a result of its antioxidant and free-radical-scavenging properties which
      in turn help to maintain the intracellular level of reduced glutathione.

PMID- 9034758
TI  - Low-dose methotrexate in the management of Chinese patients with steroid
      dependent asthma.
AB  - Nine Chinese patients with severe asthma who were dependent on a systemic oral
      steroid for control were given oral methotrexate at a dose of 7.5 mg on alternate
      days for two weeks, followed by 15 mg once weekly. Only six patients were
      evaluable; they had received methotrexate for 6 to 24 months. All six patients
      could have reduction of daily oral prednisolone dosage by 5-15 mg (mean: 10.4
      mg). Only four patients, however, had > or = 15% improvement of their best peak
      expiratory flow rates compared with baseline levels, though all six patients had
      symptomatic improvement. These beneficial effects were, however, transient and
      persisted only during methotrexate therapy. Four patients had liver enzyme
      changes and discontinuation of therapy was required in one patient. One patient
      also had infective spondylitis secondary to Salmonella bacteremia. Thus low-dose
      oral methotrexate may be useful in selected patients with severe steroid
      dependent asthma with careful monitoring for response and drug toxicity.

PMID- 9034759
TI  - Double-blind study of a multivitamin complex supplemented with ginseng extract.
AB  - To remedy the deterioration in quality of life in large cities, the addition of
      ginseng root extract to a multivitamin base appears to produce a promising
      dietary supplement. The aim of the present study was to compare the quality-of
      life parameters in subjects receiving multivitamins plus ginseng with those found
      in subjects receiving multivitamins alone. The study was comparative, randomized
      and double-blind, and it involved 625 patients of both sexes divided into two
      groups taking one capsule per day for 12 weeks. Group A received vitamins,
      minerals, trace elements and ginseng extract G115 (Pharmaton Capsules) while
      group B received vitamins, minerals and trace elements (multivitamin capsules)
      only. The resulting quality-of-life was assessed by a standardized 11-item
      questionnaire, validated by the Medical School of the National Autonomous
      University of Mexico (UNAM). Of the 625 patients recruited, 124 were excluded
      from the study due to lack of compliance with the treatment, so that 338 patients
      in group A and 163 patients in group B completed the study. By the end of the
      study, the 4th of the monthly assessments showed that both the group-A and the
      group-B treatments had induced a significant increase in the quality-of-life
      index, the change being 11.9 points for Pharmaton Capsules in group A which was
      significantly superior to the 6.4 average increase with the group-B capsules
      containing multivitamins alone. Group A showed significant improvement in every
      one of the 11 questionnaire items, whereas group B did not show significant
      improvement in any of these items. Significant increases in body weight and in
      diastolic blood pressure were recorded in the group B treated with the
      multivitamin alone. Adverse effects of the capsules were minimal in both groups.
      This study has demonstrated that Pharmaton Capsules were more effective than the
      multivitamin capsules alone in improving the quality-of-life in a population
      subjected to the stress of high physical and mental activity.

PMID- 9034760
TI  - Rapid loading of large sample volumes, analyte cleanup, and modified moving
      boundary transient isotachophoresis conditions for membrane preconcentration
      capillary electrophoresis in small diameter capillaries.
AB  - Using a removable membrane preconcentration (mPC) cartridge, large sample volumes
      can be loaded prior to final assembly of the mPC capillary electrophoresis (CE)
      capillary. For narrow-bore (< or = 25 microns ID) uncoated mPC-CE capillaries,
      applied to peptide analysis, efficient moving boundary transient isotachphoresis
      (tITP) conditions at the onset of electrophoresis are described. The enhancement
      of mPC-CE-mass spectrometry (MS) technology afforded by rapid sample loading and
      modified moving boundary tITP conditions are demonstrated by analysis of major
      histocompatibility complex (MHC) class I peptides that were derived from a Kb
      precipitation of mouse EL-4 cells. Furthermore, we demonstrate the structural
      characterization of these immunologically significant molecules by mPC-CE-tandem
      mass spectrometry (mPC-CE-MS/MS).

PMID- 9034761
TI  - The interface of capillary electrophoresis with high performance Fourier
      transform ion cyclotron resonance mass spectrometry for biomolecule
      characterization.
AB  - The interfacing of capillary electrophoresis (CE) with Fourier transform ion
      cyclotron resonance-mass spectrometry (FTICR-MS) and the factors which dictate
      obtainable performance (i.e., sensitivity, mass resolution, scan rate and duty
      cycle) are described. We demonstrate the current status of the technique with
      examples of capillary zone electrophoresis (CZE) and capillary isotachophoresis
      (CITP) with FTICR analyses of proteins and oligonucleotides, and describe current
      limitations on sensitivity and scan speed. The first on-line interfacing of
      capillary isoelectric focusing (CIEF) with FTICR is also demonstrated and shown
      to be effective for separating minor components of protein mixtures for on-line
      mass spectral analysis. Finally, the potential for greatly improved performance
      based upon recent advances in FTICR instrumentation and methods is briefly
      described.

PMID- 9034762
TI  - Probing the microheterogeneity of O-specific chains from Yersinia ruckeri using
      capillary zone electrophoresis/electrospray mass spectrometry.
AB  - The analysis of underivatized oligosaccharides arising from mild acid hydrolysis
      of endotoxins from Yersinia ruckeri serotype O2 was achieved using on-line
      capillary zone electrophoresis-electrospray mass spectrometry (CZE-ESMS). This
      technique provided unparalleled resolution of the different glycans obtained from
      purified fractions of the native endotoxins or from hydrolysis of
      lipopolysaccharides from Y. ruckeri. Electrophoretic conditions enabling the
      separation of anionic and cationic analytes were developed to determine possible
      sites of heterogeneity on either the core or the O-chain glycans. Structural
      characterization of underivatized oligosaccharides identified in the ion
      electropherograms was achieved using tandem mass spectrometry under low-collision
      energy conditions.

PMID- 9034763
TI  - Electrospray interface for capillary electrophoresis-mass spectrometry with fiber
      optic UV detection close to the electrospray tip.
AB  - A miniaturized, integrated capillary electrophoresis-ultraviolet detection
      electrospray ionization-mass spectrometry (CE-UV-ESI-MS) interface has been
      constructed and evaluated. The device incorporates a fiber optic detection cell
      close to the electrospray tip to allow UV monitoring of separated zones just
      prior to their admittance into the mass spectrometer. This configuration provides
      precise information about the time when UV-active zones enter the electrospray
      and allows easy location of analyte mass information in the ion current profile.
      The miniaturized dimensions of the interface allow the use of short capillaries
      for fast separations.

PMID- 9034764
TI  - Selecting and amplifying one fragment from a DNA fragment mixture by polymerase
      chain reaction with a pair of selective primers.
AB  - A new method for selecting and amplifying a single DNA fragment from a mixture is
      proposed. This method is applicable for the rapid classification of DNA fragments
      from a mixture and for preparation of sequencing templates. DNAs of several to
      tens of kilobases (kb) are digested with a four-base recognition restriction
      enzyme to produce smaller fragments. The complementary strand extension reactions
      are then carried out to produce fluorophore-labeled DNA fragments from the
      digestion products. These fragments can be rapidly classified according to their
      terminal-base sequences and their sizes are analyzed by capillary-array gel
      electrophoresis (CAGE). Electropherograms are used to characterize the fragments
      and to select polymerase chain reaction (PCR) primers. Any fragment in a
      digestion mixture can be amplified by PCR with a pair of primers selected from a
      primer pool by referring to the electropherograms of the fragments. This method
      was successfully used to compare the electropherograms of two different DNA
      strands and to sequence a several-kb DNA fragment without subcloning. Combined
      with CAGE, this method could be used to dramatically simplify DNA fragment
      analysis.

PMID- 9034765
TI  - Multiple capillary DNA sequencer that uses fiber-optic illumination and
      detection.
AB  - An 8-capillary prototype electrophoresis system for DNA sequencing has been
      constructed. The sequence of 400-450 bases can be obtained from each capillary in
      less than an hour from sequencing reactions generated with four-color fluorescent
      terminators. Illumination of each capillary and collection of fluorescence is
      through individual optical fibers. Resolution of the DNA ladder is through a
      replaceable sieving matrix of linear polyacrylamide in reusable coated
      capillaries. Light from an argon ion laser is introduced into a fused biconically
      tapered fiber-optic splitter, and individual fibers deliver approximately 10 mW
      of 514 nm light to each of the eight electrophoresis capillaries. Illumination
      and collection are by fibers normal to the surface of the electrophoresis
      capillary and at right angle to each other. Illumination by a fiber with low
      numerical aperture and collection by a fiber with high numerical aperture
      provides good sensitivity and signal-to-noise ratios without the need for
      microlenses (limit of detection: 1.5 x 10(-11)M fluorescein analog dye with a
      signal-to-noise ratio of 2). The eight collection fibers are passed in parallel
      through holographic filters for Rayleigh rejection and into an imaging
      spectrograph, which simultaneously displays the full fluorescence spectrum (475
      648 nm) from the eight capillaries in parallel on the surface of an intensified
      charge-coupled device (CCD). The CCD is read out at a rate of 3.4 complete images
      per second.

PMID- 9034766
TI  - DNA sequencing using a four-color confocal fluorescence capillary array scanner.
AB  - The design, construction and operation of a four-color capillary array
      electrophoresis scanner are presented. The use of sensitive energy transfer
      primers facilitates four-color detection of the DNA sequencing fragments
      following excitation at a single laser wavelength (488 nm). This scanner collects
      fluorescence data from up to 25 capillaries in parallel. The resulting four-color
      image files are automatically reduced to four-color line plots, and a base
      calling program (Sax) is used to call the sequence. The performance of this
      system for DNA sequencing is demonstrated by examining twelve different motifs of
      the hypervariable region I of human mitochondrial (mt) DNA obtained from a Sierra
      Leone population.

PMID- 9034767
TI  - The use of elevated column temperature to extend DNA sequencing read lengths in
      capillary electrophoresis with replaceable polymer matrices.
AB  - Capillary electrophoresis with a replaceable linear polyacrylamide matrix
      operated at elevated column temperatures of 55 degrees and 60 degrees C was used
      to extend the separation of DNA sequencing fragments to lengths greater than 800
      bases. A solid-state heater was employed to provide stable, uniform temperature
      control over a significant portion of the capillary. The polymer matrix, 3% w/v
      linear polyacrylamide in a denaturing buffer, was replaced in the capillary after
      each run. Using dye-labeled primers and Sequenase chemistry on an M13mp18 single
      stranded template, four-color separations for the sequencing products were
      obtained, with read lengths in excess of 800 bases. This paper also briefly
      discusses the effects of buffer denaturants and capillary temperature on
      separation speed, resolution, and gel compression.

PMID- 9034768
TI  - Efficiency of separation of DNA mutations by constant denaturant capillary
      electrophoresis is controlled by the kinetics of DNA melting equilibrium.
AB  - Constant denaturant capillary electrophoresis (CDCE) separation takes place in
      the heated portion of the capillary where faster-moving, unmelted DNA fragments
      are in equilibrium with slower-moving, partially melted forms. Within a certain
      temperature range, the position of the melting equilibrium and thus the average
      electrophoretic mobility of each mutant is different. The resulting differences
      in mobility allow sequences containing single base pair point mutations to be
      separated from each other. We report the results of experiments in which we
      explored the rules defining separation efficiency by varying the parameters of
      CDCE. We discovered an unusual peak broadening mechanism. In contrast to most
      other DNA electrophoresis systems, peak width in CDCE steadily decreases with the
      square root of the separation speed. Moreover, the peak width displays a sharp
      maximum at a specific temperature. To account for these observations, we use a
      model which describes CDCE separation as a random walk. According to this model,
      peaks in CDCE are broad because the kinetics of the melting equilibrium are slow
      and therefore the number of random walk steps represented by melting/renaturation
      transitions is relatively small. In addition to providing a satisfactory
      interpretation of the data, the model also predicts that separation efficiency
      will increase as the ionic strength of the running buffer is increased and as the
      concentration of denaturant in the buffer is decreased. These predictions were
      verified and were used to establish conditions for high-resolution CDCE suitable
      for separating complex mixtures of single base pair mutants.

PMID- 9034769
TI  - Fast capillary electrophoresis-laser induced fluorescence analysis of ligase
      chain reaction products: human mitochondrial DNA point mutations causing Leber's
      hereditary optic neuropathy.
AB  - High speed capillary electrophoresis-laser-induced fluorescence (CE-LIF) has been
      used to separate and detect point mutations using the ligase chain reaction
      (LCR). The method utilizes short capillary columns (7.5 cm effective length) and
      fields of 400 V/cm to analyze DNA-ethidium bromide complexes using an He/Ne
      laser. The method was first demonstrated with a commercially available kit for
      LCR based on a lacI gene fragment inserted in a Bluescript II phagemid. LCR-CE
      LIF was then applied to detect point mutations in human mitochondrial DNA,
      resulting in Leber's hereditary optic neuropathy (LHON). Three severe mutations
      were analyzed in which the original base is substituted by a thymidine base at
      positions 3460, 11778 and 14459. Appropriate primers were designed with polyT
      tails for length discrimination of pooled samples. Successful detection of
      mutated samples was achieved, with appropriate correction for small amounts of
      nonspecific ligated product. The method is rapid, easy to implement, and
      automatable.

PMID- 9034770
TI  - Use of wide-bore capillaries in constant denaturant capillary electrophoresis.
AB  - A serious limitation of capillary electrophoresis in separating mutant from wild
      type DNA sequences is the amount of DNA which may be loaded on narrow-bore
      columns. Because we sought to examine mutant sequences derived from more than
      10(9) human cells, we were obliged to overcome this limitation. Thus we examined
      the feasibility of using wide-bore capillaries of 250, 320 and 540 microns in
      constant denaturant capillary electrophoresis (CDCE) using conditions which
      successfully limited the effect of Joule heating. Excellent separations were
      observed using the wide-bore capillaries comparable to those obtained using a 75
      microns capillary. DNA loading capacities were increased almost 100-fold as the
      bore of capillary increased from 75 to 540 microns.

PMID- 9034771
TI  - Capillary zone electrophoresis of inorganic anions with conductivity detection.
AB  - A carrier electrolyte system for capillary zone electrophoresis (CZE) resolving
      chloride, bromide, iodide, fluoride, nitrite, nitrate, sulfate, and phosphate in
      a hydrodynamically closed separation compartment is described. The carrier
      electrolyte combines the effects of pH, polyvinylpyrrolidone (PVP) and the
      counterionic constituent on the effective mobilities of the anions. In 300
      microns ID capillary tubes made of fluorinated ethylene-propylene copolymer
      (FEP), and with detection of analytes with the aid of an alternating current
      conductivity detector, detection limits in the range of 3-10 ppb could be
      achieved for 200 nL sample volumes. The separation efficiencies were in the range
      of 1.5-2.5 x 10(5) theoretical plates per meter for an adequate sample load. The
      reproducibility was evaluated for two concentration levels. For concentrations
      close to the limits of quantitation (50-120 ppb), the RSD values ranged from 1.5
      12.6%, with the highest scatter for fluoride and phosphate. The RSD values were
      in the range of 0.4-1.5% for 300-1200 ppb concentrations of the anions. Typical
      analysis times were 2-5 min, depending on the anion species. A series of water
      samples (drinking, river, rain) was used to assess the practical applicability of
      the CZE method. The method is a suitable alternative for the determination of
      both anionic macro- and microconstituents in water with a good overall
      selectivity.

PMID- 9034772
TI  - Linearity evaluation in absorbance detection: the use of light-emitting diodes
      for on-capillary detection in capillary electrophoresis.
AB  - A model which takes into account both stray light and polychromatic light was
      used to predict and evaluate linearity in on-capillary detection in capillary
      electrophoresis (CE). According to the model the stray light is the major factor
      which determines linearity under typical CE operating conditions. By calculating
      theoretical absorbance versus concentration plots, the influence of different
      levels of stray light and polychromatic light on linearity is demonstrated.
      Experimentally, six light-emitting diodes (LEDs) in the range from 563 to 654 nm
      were examined as light sources for on-capillary detection in CE. Fitting
      theoretical curves to measured linearity plots enabled determination of the
      values of both effective path length and stray light for a particular detection
      system. The detector linearity for the four LEDs was compared to mercury and
      tungsten lamps used with interference filters. For potassium permanganate as the
      test compound, the linear range for a 563 nm LED was two times greater than that
      for a mercury lamp operated at 546 nm. The relatively poor linearity of the
      mercury lamp detector is explained by its high level of stray light. The noise of
      the LED563-based detector was the same as for the mercury lamp, whereas the other
      LEDs of higher light intensity gave approximately half the noise of the mercury
      lamp. The lowest noise level of 3 x 10(-5) AU was obtained for the LED at 554 nm
      (determined at a detector time constant of 0.1 s).

PMID- 9034773
TI  - Optimized continuous flow electrophoresis.
AB  - Continuous flow electrophoresis (CFE) was optimized by employing (i)
      electrophoretic regimes with stacking properties, to eliminate
      electrohydrodynamic dispersion, (ii) quasi-mixed zones to prevent precipitation
      of the stacked analytes, (iii) sheath liquid streams at the electrode compartment
      membranes to prevent penetration of the electrode reaction products into the
      separation chamber, (iv) proper engineering of the separation chamber to provide
      efficient dissipation of Joule heat, and (v) counterflow at the collection
      outlets to eliminate the problems of dead volumes and uneven collection of
      separated species. Data on direct temperature measurements in the separation
      chamber at various levels of the dissipated electric power are presented.
      Preparative runs of amyloglucosidase in the isoelectric focusing (IEF) mode and
      rat liver organelles in the isotochophoresis (ITP) mode demonstrate the high
      performance of the optimized CFE system.

PMID- 9034774
TI  - Rh D/d genotyping by quantitative polymerase chain reaction and capillary zone
      electrophoresis.
AB  - A safe and reliable method for determining RhD type (positive or negative) and
      zygosity (D/D or D/d) could have applications, for instance, in the prediction of
      the D genotype of a father in couples where there is an RhD-negative woman at
      risk of fetal alloimmunization. Capillary zone electrophoresis (CZE) is proposed
      as a novel, reliable and powerful method for quantitative evaluation of
      polymerase chain reaction (PCR) products. RhD is determined by amplifying a 136
      bp region common to the RhCcEe and RhD genes and a 186 bp region specific of the
      RhD gene. RhD positive and negative samples are identified by polyacrylamide gel
      slab electrophoresis, followed by silver staining of the DNA bands, and by CZE in
      sieving liquid polymers, with direct on-line peak densitometric evaluation by
      exploiting the intrinsic UV absorbance of the DNA fragments at 254 nm. The CZE
      method allows not only a reliable assessment of the RhD type (the presence of
      both 136 bp and 186 bp fragments indicating an RhD-positive type, the presence of
      only the 136 bp fragment indicating an RhD-negative type), but also a rapid
      determination of the zygosity based on the quantitative expression ratio of the
      136 bp/186 bp pair. Thus, a 2:1 peak ratio clearly indicates a D/D homozygous
      individual, whereas a 3:1 peak ratio gives evidence of a D/d heterozygous
      individual.

PMID- 9034775
TI  - Comparison of heparin-binding to lactoferrin from human milk and from human
      granulocytes by means of affinity capillary electrophoresis.
AB  - Human lactoferrin from two different sources: milk and secondary granules of
      neutrophil granulocytes, was compared with respect to heparin binding by means of
      affinity capillary electrophoresis. This method is based on analysis of migration
      pattern shifts induced by various amounts of ligand present in the
      electrophoresis buffer. Since lactoferrin is a basic molecule, analyses were
      performed at pH 8 in a capillary with a neutral hydrophilic coating. However,
      analyzable peaks were only obtained in the presence of heparin in the
      electrophoresis buffer. Proportionally to the amount of heparin present, these
      peaks exhibited shape changes and strong migration shifts. In the ensuing
      analysis it could be demonstrated that the two lactoferrins had comparable
      migration shifts and peak shape changes. This indicates that also in this respect
      the two forms of lactoferrin are identical. Affinity capillary electrophoresis is
      a convenient and fast method to investigate functional characteristics of low
      amounts of unmodified biomolecules.

PMID- 9034776
TI  - A practical procedure for the determination of association constants of the
      analyte-chiral selector equilibria by capillary zone electrophoresis.
AB  - A practical procedure is proposed for the determination of association constants
      and mobility of the associate of a solute with a chiral selector in chiral
      separations by capillary zone electrophoresis. The procedure is based on the
      measurement of the effective mobility of a solute at zero and two different
      nonzero concentrations of the chiral selector. Simple explicit formulas have been
      derived in order to calculate the required data. The essence of the procedure is
      that all mobility data are adjusted to the background electrolyte (BGE) without
      chiral selector, serving as the viscosity reference. A simple procedure is
      described for measuring the viscosity of the operational electrolytes directly
      with the commercial capillary electrophoresis instrumentation, and Walden's rule
      has been utilized for adjusting the experimental mobility data to constant
      reference viscosity. The use of the procedure is exemplified by a separation of
      D,L-tryptophan in BGE containing alpha-cyclodextrin as chiral selector.

PMID- 9034777
TI  - Determination of peptide dissociation constants and Stokes radius at different
      protonation stages by capillary electrophoresis.
AB  - Peptide electrophoretic mobility measured by capillary zone electrophoresis can
      be regarded as deriving from the mean of mobilities of different protonated
      forms, each one participating according to its charge. Stokes radius and relative
      percentage. The percentage is a function of the peptide dissociation constant and
      solution pH. Therefore, mobility modifications due to pH variations can be
      related to peptide dissociation constant, charge, and Stokes radius throughout
      general binding equations. Thus, not only can peptide dissociation constants be
      measured, but information about Stokes radius modifications linked to proton loss
      can also be obtained with picomoles of peptide.

PMID- 9034778
TI  - Optimization of selectivity and resolution in micellar electrokinetic capillary
      chromatography with a mixed micellar system of sodium dodecyl sulfate and sodium
      cholate.
AB  - Selectivity and resolution were studied for the separation of seven
      corticosteroids by micellar electrokinetic capillary chromatography (MEKC) using
      a mixed micellar solution of sodium dodecyl sulfate (SDS) and sodium cholate
      (SC), buffered with 3-(N-morpholino)propanesulfonic acid (MOPS) or 3-[(1,1
      dimethyl-2-hydroxyethyl)amino]-2-hydroxypropane sulfonic acid (AMPSO). The
      changes in selectivity were compared for the AMPSO-SDS-SC system by varying the
      pH and the concentrations of AMPSO, SDS and SC. The experimental design started
      with the central composite design and continued in a sequential manner. The
      optimum selectivity for the separation of the corticosteroids was calculated from
      the analyte migration times and the analyte velocities, by using empirical
      quadratic regression models. Satisfactory regression fits and coefficients of
      determination for prediction were obtained with cross-validated models. To
      optimize the resolution, the physical parameters of capillary length and analysis
      time were varied under the conditions optimal for the selectivity. In both the
      selectivity and the resolution, optimization the overall optimum was determined
      by using the desirability function technique. Analysis times were controlled by
      using 1,3-diaminopropane to influence the electroosmotic flow velocity (veo). The
      voltage was kept constant, which resulted in higher electric field strength in
      shorter capillaries. No changes in the selectivity were observed when 1,3
      diaminopropane was used to control the electroosmotic flow velocity. Such an
      optimization technique, where the chemical and physical factors affecting the
      separation are treated independently, seemed to be effective for finding the best
      possible resolution for the corticosteroids.

PMID- 9034779
TI  - Enantioseparation of amino acids and dipeptides using vancomycin as chiral
      selector in capillary electrophoresis.
AB  - Vancomycin was applied as chiral selector for the enantiomeric separation of
      derivatized amino acids and dipeptides. The influence of vancomycin
      concentration, pH and presence of 2-propanol in the buffer were examined in order
      to find optimal separation conditions. Optimization was by factorial design.
      Further, chiral separation of derivatives prepared with three different reagents
      was compared. These reagents were 9-fluorenylmethyl chloroformate (FMOC), 2-(9
      anthryl)ethyl chloroformate (AEOC) and dansyl chloride (dansyl). Optimum
      resolution was at high vancomycin concentrations, while optimum efficiency was at
      low vancomycin concentrations. As a consequence of the very high
      enantioselectivity of vancomycin, the vancomycin concentration below the amount
      necessary for maximal resolution can be used. Separation efficiency was
      relatively low, and this could be attributed to adsorption of the selector at the
      capillary wall. Three factors led to decreased adsorption: application of a pH
      above the zero mobility pH value, low vancomycin concentrations and the presence
      of 2-propanol. For amino acids, the resolutions of the different derivatives
      were: dansyl > AEOC > FMOC, while for dipeptides, the highest selectivity was
      with AEOC.

PMID- 9034780
TI  - Characterization of the stereoselective metabolism of methadone and its primary
      metabolite via cyclodextrin capillary electrophoretic determination of their
      urinary enantiomers.
AB  - Using capillary zone electrophoresis with a phosphate buffer at pH 3, containing
      4.3 mM hydroxypropyl-beta-cyclodextrin as chiral selector, the simultaneous
      separation of the enantiomers of methadone and its primary metabolite, 2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), is reported. After solid
      phase extraction and analysis of the reconstituted extracts in a 60 cm fused
      silica capillary of 50 microns ID within about 25 min, the mean S/R enantiomeric
      ratio of methadone in the urines of eight patients undergoing methadone therapy
      is shown to be 0.653 (range: 0.502-0.842). The mean enantiomeric ratio for the
      metabolite is 0.630 (range: 0.517-0.729). These data document the
      stereoselectivity of the methadone metabolism. Finally, the EDDP/ methadone ratio
      is shown to vary between 0.357 and 2.917 with a mean value of 1.731. The
      capillary electrophoretic assay described is simple, inexpensive and neither
      requires any sample derivatization, nor large amounts of organic solvents or
      expensive separation columns.

PMID- 9034781
TI  - Stereoselective interaction of drug enantiomers with human serum transferrin in
      capillary zone electrophoresis.
AB  - Stereoselective interaction of drugs with human serum transferrin in capillary
      zone electrophoresis is described. The substances passed a pseudo-stationary
      protein zone applied in a coated capillary and the possible chiral separation of
      the optical isomers was followed. Drugs with different structures were screened
      and the enantiomers of bupivacaine, propranolol and promethazine as well as the
      diastereomers of labetalol were resolved. Racemic mixtures of atenolol and
      pindolol enantiomers could not be resolved under these conditions.

PMID- 9034782
TI  - Separation of aracytidine and cytidine by capillary electrophoretic techniques.
AB  - Aracytidine (cytarabine, 1-beta-D-arabinofuranosylcytosine) is a synthetic analog
      of cytidine in which ribose is substituted by arabinose; it is used as a drug for
      the treatment of leukemia. A fast and reliable capillary electrophoretic method
      for the analysis of cytarabine and cytidine is described. The procedure utilizes
      the interactions with sodium dodecyl sulfate (SDS) micelles and borate, present
      in the background electrolyte, for the mobilization and selective separation of
      the analytes. The detection is carried out by UV absorbance at 275 nm. The method
      was applied both to pharmaceutical preparations and human serum. Analysis of an
      untreated serum requires 15 min; the detection limit is 0.8 microgram/mL and the
      relative standard deviation (RSD) is 5.3%.

PMID- 9034783
TI  - Application of capillary zone electrophoresis for analysis of thyreostatics.
AB  - Capillary zone electrophoresis was optimized for the separation of thiouracil,
      methylthiouracil and propylthiouracil. Methylthiouracil could be determined in
      various types of urine (human, bovine, horse), either without any pretreatment or
      in ethyl acetate extracts, within 15 min. For identification, the simultaneous
      detection at three UV wavelengths (216, 245 and 278 nm) was advantageously used
      while for quantification the wavelength of the absorbance maximum at 278 nm was
      preferred. Under optimized conditions a linear response of the detector in the
      concentration range 0.1-100 ppm was obtained. On analysis of untreated urine, a
      detection limit of 0.5 ppm was found; for urine extracts the detection limit was
      0.1 ppm. Univocal peak identification, based on absorption at three wavelength,
      was only possible above 2 ppm. Relative standard deviation for standard solutions
      of methylthiouracil, diluted in the background electrolyte, was 1%; for
      methylthiouracil in extracts dissolved in the background electrolyte it was 4.5%,
      and for methylthiouracil in untreated urine, 12.7%.

PMID- 9034784
TI  - The biology of vascular endothelial growth factor.

PMID- 9034785
TI  - Biological roles of fibroblast growth factor-2.

PMID- 9034786
TI  - Studies of gonadotropin-releasing hormone (GnRH) action using GnRH receptor
      expressing pituitary cell lines.

PMID- 9034787
TI  - Manipulation of human ovarian function: physiological concepts and clinical
      consequences.

PMID- 9034788
TI  - Premature ovarian failure and ovarian autoimmunity.
AB  - Premature ovarian failure (POF) is defined as a syndrome characterized by
      menopause before the age of 40 yr. The patients suffer from anovulation and
      hypoestrogenism. Approximately 1% of women will experience menopause before the
      age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis
      involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes.
      There remains, however, a group of POF patients without a known etiology, the so
      called "idiopathic" form. An autoimmune etiology is hypothesized for the POF
      cases with a concomitant Addison's disease and/or oophoritis. It is concluded in
      this review that POF in association with adrenal autoimmunity and/or Addison's
      disease (2-10% of the idiopathic POF patients) is indeed an autoimmune disease.
      The following evidence warrants this view: 1) The presence of autoantibodies to
      steroid-producing cells in these patients; 2) The characterization of shared
      autoantigens between adrenal and ovarian steroid-producing cells; 3) The
      histological picture of the ovaries of such cases (lymphoplasmacellular
      infiltrate around steroid-producing cells); 4) The existence of various
      autoimmune animal models for this syndrome, which underlines the autoimmune
      nature of the disease. There is some circumstantial evidence for an autoimmune
      pathogenesis in idiopathic POF patients in the absence of adrenal autoimmunity or
      Addison's disease. Arguments in support of this are: 1) The presence of cellular
      immune abnormalities in this POF patient group reminiscent of endocrine
      autoimmune diseases such as IDDM, Graves' disease, and Addison's disease; 2) The
      more than normal association with IDDM and myasthenia gravis. Data on the
      presence of various ovarian autoantibodies and anti-receptor antibodies in these
      patients are, however, inconclusive and need further evaluation. A strong
      argument against an autoimmune pathogenesis of POF in these patients is the
      nearly absent histological confirmation (the presence of an oophoritis) in these
      cases (< 3%). However, in animal models using ZP immunization, similar follicular
      depletion and fibrosis (as in the POF women) can be detected. Accepting the
      concept that POF is a heterogenous disorder in which some of the idiopathic forms
      are based on an abnormal self-recognition by the immune system will lead to new
      approaches in the treatment of infertility of these patients. There are already a
      few reports on a successful ovulation-inducing treatment of selected POF patients
      (those with other autoimmune phenomena) with immunomodulating therapies, such as
      high dosages of corticosteroids (288-292).

PMID- 9034789
TI  - 11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent
      mineralocorticoid excess.
AB  - Whereas aldosterone is normally a much stronger mineralocorticoid than cortisol
      in vivo, mineralocorticoid receptors have identical in vitro affinities for these
      hormones. The in vivo specificity of the receptors is, at least in part, the
      result of activity of 11-HSD, an enzyme located in most mineralocorticoid target
      tissues that converts cortisol to cortisone. Cortisone is not a ligand for the
      receptor, whereas aldosterone is not a substrate of the enzyme. The syndrome of
      AME is a rare form of juvenile hypertension in which 11-HSD is defective. This
      deficiency allows mineralocorticoid receptors to be occupied by cortisol, leading
      to hypertension, because plasma concentrations of cortisol are much higher than
      those of aldosterone. Licorice, which contains 11-HSD inhibitors, causes a
      similar syndrome. There are two known isozymes of 11-HSD. The liver or type I
      isozyme is expressed at high levels in the liver, has a relatively low affinity
      for steroids (micromolar Km), catalyzes both dehydrogenation and the reverse
      reductase reaction, and utilizes NADP+ or NADPH as cofactors. The kidney or type
      2 isozyme is expressed at high levels in the kidney and placenta, has a high
      affinity (nanomolar Km) for steroids, catalyzes only dehydrogenation, and
      utilizes NAD+ as a cofactor. Mutations in the HSD11B2 (HSD11K) gene encoding the
      kidney isozyme of 11-HSD have been detected in all kindreds with AME studied thus
      far. This gene represents a candidate locus for the common, "essential" form of
      hypertension.

PMID- 9034790
TI  - Immunocytochemical localization of neurofilaments in the fibre systems of the
      developing rat spinal cord white matter.
AB  - The appearance and localization of the protein subunits of neurofilaments in the
      ascending and descending fibre systems of the developing rat spinal cord white
      matter were studied. The monoclonal antibody NF-90 (specific for the
      phosphorylated NF-L, NF-M and NF-H subunits) was used as neurofilament marker in
      fresh cryostat and Bouin fixed paraffin sections. The results were compared with
      Nissl and Bodian stained sections. Within the white matter, phosphorylated
      neurofilament proteins were expressed with regional variations. At embryonal day
      12 (E12), the first positive fibres were found in the lateral funiculus. During
      further development, the peripheral region of the lateral funiculus showed an
      intense neurofilament staining, due to the presence of a higher number of fibres.
      From postnatal day 12 (P12) on, an increased amount of neurofilaments was found
      in the region close to the periphery, probably due to the presence of large
      calibre fibres. The dorsolateral part of the lateral funiculus filled in with
      fibres after birth, which indicated the extended development of the rubrospinal
      tract. At E13, positive fibres were present in the ventral commissure and the
      ventral funiculus. At E14, an increased amount of neurofilaments was detected in
      the periphery of the ventral funiculus. At maturity, an intense staining in the
      subsurface region could be found, due to the presence of large calibre fibres of
      the fasciculus longitudinalis medialis. At E13, the first neurofilament positive
      fibres were present in the dorsal funiculus. At this day, a concentration of
      fibres was found in the dorsal part of the dorsal root bifurcation zone and three
      days later, more fibres were detected in the medial part of the dorsal funiculus.
      At E18, a higher number of fibres was present in the dorsal region of the
      fasciculus gracilis. The mature fasciculus cuneatus showed an intense
      neurofilament staining, which was mainly present in large calibre fibres. The
      ventral part of the dorsal funiculus filled in with neurofilament positive fibres
      after birth. This indicated the relative late arrival of the corticospinal tract.

PMID- 9034791
TI  - Map of the Anlage fields in the avian unincubated blastoderm.
AB  - By excision at different sites of rectangular fragments from unincubated chicken
      blastoderms and replacement by isotopic fragments from unincubated quail
      blastoderms, we could make the first complete map of the Anlage fields in the
      freshly laid avian blastoderm. All the Anlage fields (Fig. 11) are found in the
      upper layer (UL) of the caudal half of the area centralis (bordered by the Rauber
      Koller's sickle). In the UL of the area marginalis, peripheral to Rauber-Koller's
      sickle, neither gastrulation nor neurulation phenomena could be observed. Similar
      heterotopic replacement experiments indicate that before incubation, the
      different parts of the UL of the area centralis are still uncommitted or
      reversibly committed. The Anlage fields of chordamesoblast and definitive
      endoderm (gut endoderm) in unincubated avian blastoderms appeared to be disposed
      caudally in the caudal half of the area centralis. As far as we know we are the
      first to demonstrate that the Anlage field of the definitive gut endoderm (which
      is derived from the upper layer: Hunt, 1937; Vakaet, 1962b) is localized in the
      most caudal upper layer part of the area centralis just centrally to the Rauber
      Koller's sickle. The Anlage field of the neural plate is localized in the upper
      layer over the more cranial endophyll. The Anlage of the brain is shield-shaped,
      whilst the other Anlage fields are sickle-shaped, parallel with the Rauber
      Koller's sickle. Their general hemicircular disposition and form still seem to
      reflect (together with the Rauber-Koller's sickle) the original ooplasmic radial
      symmetry (Callebaut, 1972) combined with the eccentricity of the deep layer
      components, which was observed during early symmetrization by gravitational
      orientation of the egg yolk (Callebaut, 1993a,b). The Rauber-Koller's sickle
      might be homologous with the vegetal dorsalizing cells or centre of Nieuwkoop
      (1973) in amphibian blastulas.

PMID- 9034792
TI  - Structure of the synaptic junctions in the rat sensorimotor cortex. Freeze
      etching study of axodendritic synapses.
AB  - The intramembranous structure of axodendritic synapses in the rat sensorimotor
      cortex was studied by means of freeze-etched replicas and thin sections. In thin
      sections, symmetric synaptic junctions were located on dendritic shafts.
      Examination of freeze-etched preparations supported the notion that the
      postsynaptic dendritic shaft membrane exhibited the same structure as the
      surrounding non-junctional membrane on both fracture faces. In thin sections,
      asymmetric perforated and non-perforated synapses were found on dendritic spines
      and dendritic shafts. In freeze-etched replicas, the postsynaptic membrane of the
      dendritic spine and some of the dendritic shaft synapses were characterized by
      perforated and non-perforated aggregates of intramembranous particles at the
      extracellular half (E-face). These aggregates are accepted as a freeze-etch
      equivalent of perforated and non-perforated asymmetric synapses seen in thin
      sections. The intramembranous characteristics of axodendritic synapses in the rat
      sensorimotor cortex are discussed in terms of synaptic contact zone plasticity.

PMID- 9034793
TI  - Microwave-antigen retrieval: the importance of pH of the retrieval solution for
      MIB-1 staining.
AB  - Using microwaves for microscopy almost invariably implies working at elevated
      temperatures. In microwave studies it became evident that high temperatures do
      not inevitably damage the tissues. On the contrary very high temperatures can
      even be beneficial. The most striking example is the 'heat shock' of formalin
      fixed paraffin sections in the microwave oven with temperatures higher than 100
      degrees C, revealing otherwise hidden epitopes. These microwave applications have
      triggered a breakthrough in pathology. The pH of the microwave-retrieval solution
      is decisive for the staining results, particularly for MiB-1. There is no
      staining of proliferating cells between pH 3.5 and 5.0. Between pH 5.0 and 6.5 we
      observed an increase in the number of MiB-1-positive stained nuclei. Our findings
      indicate that in quantitative work it is of extreme importance to standardise the
      pH of the retrieval solution and to choose pH 6.5 for optimal results.

PMID- 9034794
TI  - Microwaves in diagnostic immunohistochemistry.
AB  - Immunostaining has been shown to be clearly superior in tissues immersed in
      normal saline and fixed by primary exposure to microwaves (MWs) as compared to
      that fixed routinely in 10% buffered formalin. MWs have also been applied to dry
      cryostat sections and to accelerate antibody-antigen reactions in the staining of
      labile lymphocyte membrane antigens in such sections. MWs can also be employed to
      accelerate immunostaining in paraffin sections, producing significant reduction
      in all stages of the staining procedure. The more recent application of MWs for
      epitope retrieval has made an important step towards not only producing better
      immunostaining of routinely fixed tissues but also towards the standardisation of
      the immunostaining process. MW-irradiation of paraffin-embedded sections in 10
      mMol citrate buffer solution produced, with few exceptions, increased intensity
      and extent of immunostaining of a wide variety of tissue antigens. Moreover,
      proteolytic enzyme digestion was not necessary in most instances and some primary
      antibodies could be used at higher working dilutions.

PMID- 9034795
TI  - Microwave fixation method for cytochemistry. For conventional electron
      microscopy, enzymo-immunocytochemistry, autoradiography elemental distribution
      studies and staining methods.
AB  - More than a decade ago, we introduced a microprocessed household microwave oven
      for microwave-stimulated fixation. In this paper we present an overview of our
      experience. We have introduced the use of tannic acid (TA, 0.1%), which is very
      effective for fixing soluble peptides or proteins, except in the case of enzymo
      cytochemistry. In the latter case, a combination of TA with aldehyde in the
      microwave-fixation step brings perfect fixation, but inactivation of the enzymes
      and their enzymatic activities.

PMID- 9034804
TI  - Time study of psychiatric emergency service evaluations.
AB  - The study of consultation time at the Psychiatric Emergency Service (PES) can be
      a valuable guide to allocation of resources in a time of scarcity. Most reports
      have dealt with the duration of evaluations in the medical emergency room, but
      more comprehensive PES services use separate space, staff, and 'holding units' to
      allow proper handling of the psychiatric emergency. The purpose of this study was
      to determine what factors influence the time course of PES consultations.
      Consecutive evaluations done at the PES during the first quarter of 1995 (N =
      895) were reviewed. Analysis of variance with multiple comparisons and multiple
      linear regression techniques were used to select out significant variables and
      quantify their contribution to time of evaluation. Waiting times to receive
      psychiatric services were longer on day and evening shifts, compared with the
      night shift. Substance abuse diagnosis, police/ mobile team referral, and the
      need for emergency medication also lengthened waiting times. Contact time to
      deliver psychiatric services was longer during the busy evening shift. It was
      longer if emergency medication had to be administered, if hospitalization had to
      be provided, or if the patient had past hospitalization history. The duration of
      psychiatric evaluations was greatly affected by the high acuity patient who may
      require management of disturbed behavior. This is different from the situation in
      medical ERs when the low acuity patient has the longest delays. The medical
      literature describes sources of delay in terms of waiting for lab tests,
      consults, and computed tomography results, whereas in the PES behavior management
      fills this role.

PMID- 9034805
TI  - Domestic violence in the Emergency Department: I. Two case-control studies of
      victims.
AB  - The object of this study was to compare the diagnoses and characteristics of self
      reported domestic violence victims with a random sample of nonvictim controls who
      were selected from attendees at the Emergency Department (ED) of a major public
      hospital in Australia. Comparisons were made at index presentation and for the 5
      years prior to index presentation. Subjects were drawn from two screening studies
      carried out 1 year apart which were conducted to assess the prevalence of
      domestic violence among attendees at the ED. From these groups, the medical
      records of all individuals who had disclosed domestic violence were examined and
      compared with the medical records of a random sample of nondisclosers, matched
      for age (+/- 10 years), sex, and type of entry into the ED (acute vs nonacute).
      The two case-control studies, conducted 12 months apart, showed that there were
      statistically significant differences between the diagnoses and characteristics
      of victims and nonvictims. Victims made more visits to the ED and Outpatients'
      Department than nonvictims; victims had more psychiatric index presentations;
      more victims had evidence of treatment of psychiatric conditions, both as
      inpatients and outpatients, in the previous 5 years than nonvictims; victims had
      greater rates of attempted suicide and alcohol problems than nonvictims at index
      presentation and for the previous 5 years. The findings indicate the need for the
      prevention and treatment of psychiatric conditions of domestic violence victims,
      including drug and alcohol problems and suicidal ideation. The findings form the
      basis of hypotheses for further studies to investigate the association between
      domestic violence and psychiatric illness.

PMID- 9034806
TI  - Domestic violence in the Emergency Department: 2. Detection by doctors and
      nurses.
AB  - This study was conducted in 1991 and 1992 to determine the detection rates of
      domestic violence victims by doctors and nurses at the Emergency Department (ED)
      of Royal Brisbane Hospital, a major public hospital in Australia. The objective
      was to determine the outcome of an education program about domestic violence
      conducted in 1991 for doctors and nurses in the ED. As part of two case-control
      studies, the self-reports of those who disclosed domestic violence on a screening
      questionnaire were compared with the recording of domestic violence on each
      individual medical record. Subjects were drawn from two screening studies carried
      out 1 year apart which were conducted to assess the prevalence of domestic
      violence among attendees at the ED. An education program about domestic violence
      was conducted for doctors and nurses in the ED between the two screening studies.
      The examination of the medical records showed that detection rates of victims of
      domestic violence were unchanged between the two case-control studies. Both
      studies found that 50.0% of those who reported the experience of domestic
      violence within the 24 hours prior to index presentation, on the screening
      questionnaire in the prevalence studies, were recorded as such in their medical
      records. The low detection rates indicate the requirement for doctors and nurses
      to receive appropriate training to identify and record the psychosocial aspects
      of domestic violence victims. As well as training, referral systems need to be
      set in place to address the psychosocial aspects of domestic violence victims.

PMID- 9034807
TI  - The multisite field trial of the consultation-liaison psychiatry assessment
      instrument.
AB  - A multisite field trial was conducted at 11 institutions to test the clinical
      reliability of a 29-item consultation-liaison (C-L) psychiatry assessment
      instrument. Twenty-five raters viewed videotapes of two "trainees" conducting
      clinical interviews with a simulated patient. One trainee was a medical student,
      the other was a fellow in psychiatry. Raters completed the 29-item assessment
      instrument for each trainee. The mean value scores reflected the skill of each
      trainee. The medical student had a mean score of 1.93, whereas the C-L fellow had
      a mean score of 3.13 which parallels the expected level of skill for the two
      interviewers. Eighty-six percent of the items (25/29) had a standard deviation
      (SD) of less than 1.0. Each of the remaining four items (14%) had a SD minimally
      greater than 1.0. These results reflect clear wording of items with measurable
      parameters defined for assessing trainees' skills. The authors present different
      uses for the assessment instrument, including giving feedback to trainees
      regarding interviewing techniques and skills; setting "gold" and "lead" standards
      for clinical C-L interviewing skills; and training supervisors in evaluation
      using a standardized assessment instrument.

PMID- 9034808
TI  - Concurrent factitious disorder and factitious disorder by proxy. Double jeopardy.
AB  - Two forms of medical dissimulation-factitious disorder and factitious disorder by
      proxy-present enormous challenges to clinicians accustomed to receiving valid
      symptom reports from their patients. The consequences of such "disease forgery"
      are heightened when a patient simultaneously engages in both forms of deception.
      We discuss a 34-year-old nurse who simulated or induced a panoply of physical and
      psychological ailments in both herself and her daughter. The staff's insistence
      on access to outside information sources proved indispensible in establishing
      both diagnoses, facilitating ongoing treatment for the patient and ensuring
      appropriate protection of the child.

PMID- 9034809
TI  - Psychiatric illness in patients referred to a dermatology-psychiatry clinic.
AB  - There is a recognized psychiatric morbidity among those who attend dermatology
      clinics. We aimed to determine the pattern of psychological and social problems
      among patients referred to a liaison psychiatrist within a dermatology clinic.
      Notes from 149 patients were reviewed and more detailed assessments performed in
      a subgroup of 32 consecutive referrals. All but 5% merited a psychiatric
      diagnosis. Of these, depressive illness accounted for 44% and anxiety disorders,
      35%. Less common general psychiatric disorders included social phobia,
      somatization disorder, alcohol dependence syndrome, obsessive-convulsive
      disorder, posttraumatic stress disorder, anorexia nervosa, and schizophrenia.
      Classical disorders such as dermatitis artefacta and delusional hypochondriasis
      were uncommon. Commonly, patients presented with longstanding psychological
      problems in the context of ongoing social difficulties rather than following
      discrete precipitants. Psychiatric intervention resulted in clinical improvement
      in most of those followed up. Of the dermatological categories 1) exacerbation of
      preexisting chronic skin disease; 2) symptoms out of proportion to the skin
      lesion; 3) dermatological nondisease; 4) scratching without physical signs, the
      commonest were dermatological nondisease and exacerbation of chronic skin
      disease. Anxiety was common in those from all dermatological categories. Patients
      with dermatological nondisease had the highest prevalence of depression. Skin
      patients with significant psychopathology may go untreated unless referred to a
      psychiatrist. The presence of dermatological nondisease or symptoms out of
      proportion to the skin disease should particularly alert the physician to the
      possibility of underlying psychological problems.

PMID- 9034810
TI  - The feasibility of a new intake routine to assess substance use disorders by
      means of a structured interview.
AB  - A structured interview, ADDIS (Alkohol Drog Diagnos InStrument), designed to
      assess substance use disorders, was included as a part of the intake protocol in
      a department of orthopedics at a general hospital. To evaluate both the
      effectiveness and feasibility of the new procedure, the attitudes of 29 staff
      members were sampled during follow-up interviews. In addition, a questionnaire
      was sent to 254 patients to examine their opinions about the interview. The staff
      made a global evaluation of the new routine on a 10-point scale, ranging from
      completely negative (1) to completely positive (10). The mean rating was 8.2
      (range 5-10). The evaluations made by the staff members in the interviews were
      very positive. Of the 254 patients, 177 (70%) returned the questionnaire. More
      than 90% of the patients appreciated being asked about their use of analgesics
      and sedatives, and 77% felt it was positive to be asked about their alcohol use.
      The result of the patient questionnaire supports the feasibility of the routine,
      suggesting that a structured interview can be included in the intake protocol in
      order to improve the assessment of substance use disorders.

PMID- 9034811
TI  - Cognitive therapy with inpatients.
AB  - Psychotherapeutic interventions often play a major role in the treatment of
      patients who are hospitalized for depression. Much of the "therapeutic milieu" of
      the inpatient unit includes patient participation in group psychotherapy and in
      one-on-one psychotherapy with staff members. These interventions are designed not
      only to be primary treatments for depression, but are also used to enhance
      patients' compliance with pharmacotherapy. Cognitive therapy (CT) has been
      adapted for use with inpatients and has been used as an organizing theory for the
      hospital milieu in several inpatient units. Research on inpatient CT suggests
      that it is a beneficial treatment that enhances continuity of care after
      discharge from the hospital. This paper describes the general principles of
      inpatient CT, and discusses the various types of inpatient cognitive therapy
      units (CTUs) that have been developed. The benefits of such programs are
      described, and research regarding the effectiveness of inpatient CT is discussed.

PMID- 9034812
TI  - Profiles and treatment of attempted suicide by self-immolation.
AB  - Self-immolation represented 3.9% of patients (N = 7) at this burn unit over the
      last 18 months. Charts of these patients were retrospectively reviewed for
      demographics, hospital course, and discharge plan. All had a major psychiatric
      diagnosis, although no clear patient profile emerged. These patients required
      complex individualized care, but the psychosocial treatment challenges had many
      common elements. Psychiatric aspects of these patients proved problematic for the
      burn unit staff. Physical sequelae of the burns raised problems in arranging
      subsequent psychiatric treatment. Follow-up information was obtained by brief
      telephone interviews. The survivors appeared to be functioning well given their
      psychopathology and physical sequelae.

PMID- 9034813
TI  - Selection bias in an inpatient outcomes monitoring project.
AB  - Managed care organizations increasingly tout clinical outcomes assessment as the
      mechanism by which we will ensure quality and compare providers. The authors
      report on their experience with a multisite inpatient outcomes monitoring project
      by comparing patients who accepted (N = 51), refused (N = 36), or were not asked
      (N = 110) to participate in the project. The patients who were asked to
      participate had significantly longer inpatient stays compared with the unasked
      group (11.2 vs 6.9 days). Patients who agreed to participate in the project were
      more likely to have a bipolar (43.1% vs 19.2%) or any affective disorder (94.1%
      vs 79.5%), and less likely to have a schizophrenic disorder (2.0% vs 11.6%) than
      the refused and unasked groups. The project participants also had higher 90-day
      readmit rates (27.5% vs 9.6%), more readmissions (0.51 vs 0.16), and more
      education (14.59 vs 13.51 years) than nonparticipating patients. In this
      preliminary study, patient-related variables were found to influence who the
      staff asked and who consented to participate in this clinical outcomes monitoring
      project. The authors distinguish clinical outcomes monitoring from treatment
      effectiveness research and discuss the need to develop methodologies that deal
      with nonrepresentative patient sampling and intersite variability in recruitment
      practices.

PMID- 9034814
TI  - Eating attitudes and the irritable bowel syndrome.
AB  - A series of 48 new patients with irritable bowel syndrome (IBS) were asked to
      complete an Eating Attitudes Test. The same test was given to a series of 32
      patients attending an Eating Disorder clinic, a series of 31 patients attending a
      gastroenterology outpatient clinic with a diagnosis of inflammatory bowel disease
      (IBD), and to a group of 28 'normal' controls. The results showed that there was
      no significant difference between the IBD group and control groups for EAT score.
      The EAT score for the group with eating disorders was significantly higher than
      for all other groups. The EAT score for the IBS group was greater than those for
      the IBD and control group (p = 0.05) when all four groups were compared using
      analysis of variance and the Least Significant Difference test.

PMID- 9034826
TI  - Early activation of microglia in the pathogenesis of fatal murine cerebral
      malaria.
AB  - Microglia are pluripotent members of the macrophage/monocyte lineage that can
      respond in several ways to pathological changes in the central nervous system. To
      determine their role in the pathogenesis of fatal murine cerebral malaria (FMCM)
      we have conducted a detailed study of the changes in morphology and distribution
      of retinal microglia during the progression of the disease. Adult CBA/T6 mice
      were inoculated with Plasmodium berghei ANKA. These mice died 7 days post
      inoculation (p.i.) with the parasite while exhibiting cerebral symptoms,
      increased permeability of the blood-brain barrier, and monocyte adherence to the
      vascular endothelium. Mice were injected i.v. with Monastral blue 2 h prior to
      sacrifice to identify "activated" monocytes, and their isolated retinae were
      incubated with the Griffonia simplicifolia (GS) lectin or reacted for the
      nucleoside diphosphatase enzyme to visualize microglia and the vasculature.
      Changes in microglial morphology were seen within 2-3 days p.i., that is, at
      least 3 days prior to the onset of cerebral symptoms and 4 days before death.
      Morphological changes included retraction of ramified processes, soma
      enlargement, an increasingly amoeboid appearance, and vacuolation. There was also
      increased staining intensity and redistribution of "activated" microglia toward
      retinal vessels, but no increase in density of NDPase-positive cells. The GS
      lectin only labeled a small population of microglia in the uninfected adult mouse
      retina. However, there was a striking increase in the focal density of GS
      positive microglia during the progression of the disease. Extravasation of
      monocytes also was observed prior to the onset of cerebral symptoms. These
      results provide the first evidence that microglial activation is a critical
      component of the pathological process during FMCM.

PMID- 9034827
TI  - Dying-back oligodendrogliopathy: a late sequel of myelin-associated glycoprotein
      deficiency.
AB  - Ultrastructural analysis of myelin from 8-month-old mice deficient in the myelin
      associated glycoprotein revealed pronounced and characteristic alterations of the
      periaxonal oligodendrocyte processes, consisting of intracytoplasmic deposition
      of vesicular material, multivesicular bodies, mitochondria, and lipofuscin
      granules, as well as granular or paracrystalline inclusions. These alterations
      are similar to those described before as "dying-back oligodendrogliopathy" in
      diseases of toxic or immune-mediated demyelination including multiple sclerosis.

PMID- 9034828
TI  - Intracellular acidification of the leech giant glial cell evoked by glutamate and
      aspartate.
AB  - Glutamate is an excitatory receptor agonist in both neurones and glial cells,
      and, in addition, glutamate is also a substrate for glutamate transporter in
      glial cells. We have measured intracellular and extracellular pH changes induced
      by bath application of glutamate, its receptor agonist kainate, and its
      transporter agonist aspartate, in the giant neuropile glial cell in the central
      nervous system of the leech Hirudo medicinalis, using double-barrelled pH
      sensitive microelectrodes. The giant glial cells responded to glutamate and
      aspartate (100-500 microM), and kainate (5-20 microM) with a membrane
      depolarization or an inward current and with a distinct intracellular
      acidification. Glutamate and aspartate (both 500 microM) evoked a decrease in
      intracellular pH (pHi) by 0.187 +/- 0.081 (n = 88) and 0.198 +/- 0.067 (n = 86)
      pH units, respectively. With a resting pHi of 7.1 or 80 nM H+, these
      acidifications correspond to a mean increase of the intracellular H+ activity by
      42 nM and 45 nM. Kainate caused a decrease of pHi by 0.1-0.35 pH units (n = 15).
      The glutamate/aspartate-induced decrease in pHi was not significantly affected by
      the glutamate receptor blockers kynurenic acid (1 mM) and 6-cyano-7
      dinitroquinoxaline-2,3-dione (CNQX, 50-100 microM), which greatly reduced the
      kainate-induced change in pHi. Extracellular alkalinizations produced by
      glutamate and aspartate were not affected by CNQX. Reduction of the external Na+
      concentration gradually decreased the intracellular pH change induced by
      glutamate/aspartate, indicating half maximal activation of the acidifying process
      at 5-10 mM external Na+ concentration. When all external Na+ was replaced by
      NMDG+, the pHi responses were completely suppressed (glutamate) or reduced to 10%
      (aspartate). When Na+ was replaced by Li+, the glutamate- and aspartate-evoked
      pHi responses were reduced to 18% and 14%, respectively. Removal of external Ca2+
      reduced the glutamate- and aspartate-induced pHi responses to 93 and 72%,
      respectively. The glutamate/aspartate-induced intracellular acidifications were
      not affected by the putative glutamate uptake inhibitor amino-adipidic acid (1
      mM). DL-aspartate-beta-hydroxamate (1 mM), and dihydrokainate (2 mM), which
      caused some pHi decrease on its own, reduced the glutamate/aspartate-induced pHi
      responses by 40 and 69%, respectively. The putative uptake inhibitor DL-threo
      beta-hydroxyaspartate (THA, 1 mM) induced a prominent intracellular acidification
      (0.36 +/- 0.05 pH units, n = 9), and the pHi change evoked by glutamate or
      aspartate in the presence of THA was reduced to less than 10%. The results
      indicate that glutamate, aspartate, and kainate produce substantial intracellular
      acidifications, which are mediated by at least two independent mechanisms: 1) via
      activation of non-NMDA glutamate receptors and 2) via uptake of the excitatory
      amino acids into the leech glial cell.

PMID- 9034829
TI  - Stimulation of glutamate uptake and Na,K-ATPase activity in rat astrocytes
      exposed to ischemia-like insults.
AB  - The postsynaptic actions of glutamate are rapidly terminated by high affinity
      glutamate uptake into glial cells. In this study we demonstrate the stimulation
      of both glutamate uptake and Na,K-ATPase activity in rat astrocyte cultures in
      response to sublethal ischemia-like insults. Primary cultures of neonatal rat
      cortical astrocytes were subjected to hypoxia, or to serum- and glucose-free
      medium, or to both conditions (ischemia). Cell death was assessed by propidium
      iodide staining of cell nuclei. To measure sodium pump activity and glutamate
      uptake, 3H-glutamate and 86Rb were both simultaneously added to the cell culture
      in the presence or absence of 2 mM ouabain. Na,K-ATPase activity was defined as
      ouabain-sensitive 86Rb uptake. Concomitant transient increases (2-3 times above
      control levels) of both Na,K-ATPase and glutamate transporter activities were
      observed in astrocytes after 4-24 h of hypoxia, 4 h of glucose deprivation, and 2
      4 h of ischemia. A 24 h ischemia caused a profound loss of both activities in
      parallel with significant cell death. The addition of 5 mM glucose to the cells
      after 4 h ischemia prevented the loss of both sodium pump activity and glutamate
      uptake and rescued astrocytes from death observed at the end of 24 h ischemia.
      Reoxygenation after the 4 h ischemic event caused the selective inhibition of
      Na,K-ATPase activity. The observed increases in Na,K-ATPase activity and
      glutamate uptake in cultured astrocytes subjected to sublethal ischemia-like
      insults may model an important functional response of astrocytes in vivo by which
      they attempt to maintain ion and glutamate homeostasis under restricted energy
      and oxygen supply.

PMID- 9034830
TI  - Compromised blood-nerve barrier, astrogliosis, and myelin disruption in optic
      nerves during fatal murine cerebral malaria.
AB  - We examined the optic nerve, as an analogous tissue to brain white matter, to
      assess possible relationships between changes in the blood-nerve barrier, axonal
      integrity, and astrocyte morphology in the central nervous system during fatal
      murine cerebral malaria (FMCM). In the FMCM model, namely, CBA mice infected with
      Plasmodium berghei ANKA, neurological symptoms begin around day 5 post
      inoculation (p.i.) and mice become increasingly ill by day 7 p.i., at which time
      they lapse into coma and die. Using intravascular perfusion with horseradish
      peroxidase combined with light and electron microscopy, and GFAP
      immunohistochemistry, the optic nerves in malaria-infected mice were found to
      display i) breakdown of the blood-nerve barrier, detectable as early as day 3
      p.i. (about 2 days before the onset of neurological symptoms) increasing to peak
      severity by day 7 p.i.; ii) monocytosis, vascular congestion, and monocyte
      adherence to the endothelium in the microvasculature during the later stages of
      the disease process; iii) an increased incidence of patchy axonal demyelination
      and degeneration, mostly associated with vascular changes and astrogliosis,
      beginning at day 5 p.i. and more evident by day 7 p.i.; and iv) an increased
      intensity of GFAP immunostaining, detectable from day 3 p.i. and peaking at day 7
      p.i. These optic nerve changes were always seen in the infected individuals,
      though they varied in intensity. The temporal and anatomical coincidence between
      the compromised blood-nerve barrier, monocyte adherence to the vascular
      endothelium, astrocyte changes, neuronal degeneration, and demyelination in the
      optic nerve in FMCM suggests that these factors are mechanistically inter
      related. These findings are consistent with the proposed immunopathological
      nature of FMCM and provide further evidence for the pivotal role of the CNS
      microvasculature in the disease process. This is the first investigation of
      involvement of the optic nerve in FMCM and the first demonstration, to our
      knowledge, of loss of axonal viability in this condition in any CNS tissue. The
      observed demyelination is consistent with reports by other workers on such
      changes in the brain in human cerebral malaria.

PMID- 9034831
TI  - Inducible nitric oxide synthase expression in activated rat microglial cultures
      is downregulated by exogenous prostaglandin E2 and by cyclooxygenase inhibitors.
AB  - Prostaglandins and nitric oxide (NO) are among the numerous substances released
      by activated microglial cells, the brain resident macrophages, and they mediate
      several important microglial functions. We have previously shown that
      cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), the two key enzymes in
      prostaglandin and NO synthesis, respectively, are rapidly co-induced in rat
      neonatal microglial cultures activated by bacterial endotoxin (lipopolysaccharide
      [LPS]) and that COX-2 expression appears to be under the negative control of
      endogenous as well as exogenous NO. In this study we show that exogenous
      prostaglandin E2 (PGE2), which is known to increase cyclic adenosine
      monophosphate (cAMP) levels in microglial cells, downregulates LPS-induced iNOS
      expression in a dose-dependent manner. The involvement of cAMP in the PGE2
      dependent inhibition of iNOS is supported by several pieces of evidence. First,
      iNOS expression was also inhibited by agents such as isoproterenol and forskolin,
      which cause an elevation of cAMP levels, and by dibutyryl cAMP (dbcAMP), a cAMP
      stable analogue. Second, the inhibitory effect of PGE2 was mimicked by 11-deoxy
      16,16-dm PGE2, a selective agonist at the PGE2 receptor subtype EP2, coupled to
      the activation of adenylyl cyclase, but not by sulprostone, a potent agonist at
      receptor subtypes EP3 and EP1, associated with an inhibition of adenylyl cyclase
      activity and intracellular Ca2+ elevation, respectively. Third, the inhibitory
      effect of PGE2 on NO synthesis was blocked by SQ 22,536, a specific inhibitor of
      adenylyl cyclase. Interestingly, the abrogation of endogenous prostanoid
      production by several COX inhibitors caused a reduction of iNOS expression,
      suggesting a positive modulatory effect of endogenous prostanoids of iNOS
      expression, as opposed to the inhibitory effect of exogenous PGE2.

PMID- 9034832
TI  - Different voltage-gated sodium currents are expressed by human neuroblastoma NB69
      cells when cultured in defined serum-free and in astroglial-conditioned media.
AB  - Voltage-gated Na+ currents (INa) were analysed with the whole-cell patch-clamp
      technique in human neuroblastoma NB69 cells plated in serum-free "defined" medium
      (DM) or in "astroglial-conditioned" medium (CM). Cells survived in both media and
      expressed the microtubule associated protein 1A, indicating neuron-like
      differentiation. Two INa types with different time-, voltage-dependent properties
      and tetrodotoxin (TTX) sensitivities were expressed in DM and CM. The INa in DM
      plated cells was present from day 4 and its surface density increased from 11
      pA/pF (days 5-7) to 68 pA/pF (days 15-30). The underlying conductance (GNa) half
      activated (V0A) at -24 mV. INa inactivation was fitted by single exponentials
      with 7.5 ms time constant (th) at the -35 mV half-inactivation voltage (V0I). INa
      was not affected by 10 nM, was reduced (65%) by 100 nM, and not completely
      abolished (92%) by 300 nM tetrodotoxin (TTX). The INa of CM-plated cells appeared
      at day 3-4 and its surface density increased from 14 pA/pF (days 3-6) to 28 pA/pF
      (days 11-14). The GNa V0A was -29 mV and inactivation was fitted by single
      exponentials with 2.6 ms that the -58 mV V0I. This INa was reduced (55%) by 10 nM
      and totally abolished by 100 nM tetrodotoxin (TTX). In conclusion, NB69 cells
      displayed a slow, "TTX-resistant," or a fast, "TTX-sensitive" INa in DM and CM,
      respectively, suggesting that the CM contained diffusible trophic factors of
      astroglial origin that induced the expression of a different Na+ channel type.
      About half of the CM- and DM-plated cells also displayed a persistent Na+ current
      (INaP).

PMID- 9034833
TI  - Astrocytes, not neurons, show most prominent staining for spermidine/spermine
      like immunoreactivity in adult rat brain.
AB  - Polyamines are involved in a variety of basic cellular functions including
      proliferation and differentiation. Recent in vitro evidence suggests a role for
      spermidine or spermine as possible modulators of ionotropic glutamate receptors
      and inwardly rectifying potassium channels. However, before a functional role of
      spermidine or spermine in vivo can be considered, the presence of these
      polyamines in the mammalian central nervous system must be demonstrated. Here we
      report the localization of spermine/spermidine-like immunoreactivity in the major
      cell types of the adult rat brain, using polyclonal antibodies raised against
      glutaraldehyde-conjugated spermine. Neuronal staining was restricted to several
      discrete brain nuclei and was generally weak. In the hippocampus,
      immunoreactivity was found in the area of perforant path terminals and in the
      CA2/CA3 subfields. The CA1 region and the area of the mossy fiber terminals was
      largely negative. Throughout the brain, the most prominent staining was displayed
      by astrocytes, as confirmed by comparison with astrocyte and microglial markers,
      but immunolabel was also detected in oligodendrocytes and pericytes. Their
      intense staining for spermidine/spermine-like immunoreactivity suggests that
      astrocytes are the most likely source for extracellular polyamines in the rat
      brain.

PMID- 9034834
TI  - Horizontal transposition of vertical rectus muscles for treatment of
      excyclotropia.
AB  - BACKGROUND: Horizontal transposition of the vertical rectus muscles has been
      performed for treatment of excyclotropia associated with congenital absence of
      the superior oblique, and for residual excyclotropia after the Harada-Ito
      operation. However, the amount of excyclotropia that can be corrected and whether
      this technique alters the vertical muscle balance is not well known. We report
      the surgical results of three patients with pure excyclotropia who underwent
      unilateral one-half tendon width horizontal transpositions of vertical rectus
      muscles. METHODS: A one-half muscle width temporal transposition of the superior
      rectus and nasal transposition of the inferior rectus muscles of one eye was
      performed in three patients with pure excyclotropia and no associated
      hypertropia. All three had intermittent torsional diplopia before surgery.
      RESULTS: Postoperatively, excyclotropia decreased significantly in all fields of
      gaze, with 8 degrees of reduction by synoptophore and 12.3 degrees of reduction
      by fundus photography on average. There was no associated vertical or horizontal
      deviation. All three patients reported improvements of cyclofusion. CONCLUSION:
      One-half muscle width temporal transposition of the superior rectus and nasal
      transposition of the inferior rectus muscles was effective in ameliorating
      excyclotropia and corrected subjective complaints without altering vertical
      muscle balance.

PMID- 9034835
TI  - Characteristics of endogenous uveitis in Hokkaido, Japan.
AB  - BACKGROUND: Etiological characteristics of endogenous uveitis vary among areas
      and races around the world. There are few epidemiological reports on the etiology
      of uveitis from areas within Asia. We report statistical data on uveitis in
      Japan. METHODS: We reviewed all of the records of patients with endogenous
      uveitis who visited the Uveitis Survey Clinic of Hokkaido University Hospital in
      1981 and 1994 and extended the survey to include new patients with uveitis seen
      over the 3-year period from 1992 to 1994. RESULTS: Bechcet's disease, sarcoidosis
      and Vogt-Koy-anagi-Harada disease were the three most frequently diagnosed
      diseases in both 1981 and 1994. The proportion of patients with unclassified
      uveitis decreased from 38% to 30% during the 13-year period from 1981 to 1994 as
      a result of the establishment of new disease categories during this time. Notable
      additions included human T-lymphotropic virus type 1-associated uveitis and
      tubuloinerstitial nephritis and uveitis syndrome. Sarcoidosis is now the most
      frequent endogenous uveitis in our clinic. CONCLUSION: Not only does the
      etiological basis of uveitis vary among ethnic groups but advances in clinical
      and basic research have changed the diagnostic approach to uveitis, altering the
      etiological profile over time.

PMID- 9034836
TI  - Thrombus and branch retinal vein occlusion.
AB  - Branch retinal vein occlusion (BRVO) is often associated with arteriosclerosis.
      Typically the occlusion occurs at an arteriovenous crossing. We report a case of
      a previously healthy patient who developed a BRVO. Funduscopy and fluorescein
      angiography suggested an intravascular thrombus as the cause of the occlusion.
      The investigations performed were positive for systemic hypertension and
      hyperlipidaemia. After 2 months, fundus examination revealed disappearance of the
      intravascular thrombus, resolution of the macular edema and improvement of the
      visual acuity. Certain physiological characteristics of the retinal circulation
      associated with hyperlipidaemia and systemic hypertension appear to favour
      thrombus formation.

PMID- 9034837
TI  - Application of HELP in nonarteritic anterior ischemic optic neuropathy: a
      prospective, randomized, controlled study.
AB  - BACKGROUND: Heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP)
      eliminates selectively fibrinogen, LDL, cholesterol, triglycerides and LP(a) from
      blood plasma using extracorporeal circulation. The reduction of fibrinogen and
      LDL by about 50% after only one procedure immediately improves the
      hemorheological situation. METHOD: In a prospective, randomized, controlled study
      over a period of 3 months, 40 patients with nonarteritic ischemic optic
      neuropathy (NAION) were randomly assigned to either HELP or hemodilution therapy
      to determine the efficacy of these two treatments on visual acuity and fields.
      RESULTS: After transformation of the Snellen acuity into logMAR units the
      statistical analysis did not show a significant difference between the two groups
      (P = 0.48). An increase of the visual acuity by two or more lines was obtained in
      9 patients (47.4%) of the HELP group, 10 (52.6%) remained stable and none got
      worse. In the hemodilution group, visual acuity increased in patients (33.4%), 9
      (42.8%) remained stable and 5 (23.8%) experienced a decrease. The calculated mean
      sensitivity of visual fields at baseline improved statistically significantly (P
      < 0.01) in the HELP group from 6.83 +/- 4.52 dB to 8.27 +/- 4.89 dB, but did not
      change significantly in the hemodilution group (6.25 +/- 4.12 dB to 6.12 +/- 3.92
      dB). CONCLUSION: The HELP system seems to be safe and more effective than
      hemodilution in improving the hemorheological and the functional situation in
      NAION and could be a promising regimen in the treatment of NAION.

PMID- 9034838
TI  - The effect of latanoprost 0.005% once daily versus 0.0015% twice daily on
      intraocular pressure and aqueous humour protein concentration in glaucoma
      patients. A randomized, double-masked comparison with timolol 0.5%.
AB  - BACKGROUND: Latanoprost is a PGF2 alpha analogue which reduces the intraocular
      pressure (IOP) by increasing the uveoscleral outflow. The objective of this study
      was to investigate the effect of two different regimens of latanoprost on the
      diurnal IOP and also the effect of latanoprost on the blood-aqueous barrier
      measured with a laser flare cell meter (Kowa FM-500). Moreover, the safety
      aspects of the two regimens regarding hyperemia were studied. METHODS: A double
      masked, randomized study was performed in 30 patients (9 males, 21 females; mean
      age 61.9 years) with primary open-angle glaucoma or pseudoexfoliation glaucoma.
      Twenty patients were treated with latanoprost 0.0015% twice daily or 0.005% once
      daily for 3 weeks in a cross-over design. Ten patients received timolol 0.5%
      twice daily as control. RESULTS: Latanoprost 0.005% once daily reduced IOP (+/-
      SEM) more effectively than latanoprost 0.0015% twice daily (9.8 +/- 0.9 mm Hg and
      6.7 +/- 0.9 mm Hg, respectively). There was a statistically significant increase
      in the aqueous humour protein concentration within the timolol group (P = 0.004),
      but not within the latanoprost group (P = 0.97). There was no statistically
      significant difference in the change in aqueous humour protein concentration from
      baseline between latanoprost and timolol groups (P = 0.08). No statistically
      significant difference in conjunctival hyperemia between the two latanoprost
      regimens was found (P = 0.37). CONCLUSION: Latanoprost 0.005% once daily reduced
      IOP more effectively than latanoprost 0.0015% twice daily (P < 0.001).
      Latanoprost had no statistically or clinically significant effect on the blood
      aqueous barrier. There was no difference in hyperemia between the two regimens.
      Both concentrations of latanoprost reduced IOP at least as well as timolol 0.5%
      eye drops.

PMID- 9034839
TI  - Visualization of retinal and choroidal blood flow with fluorescein leukocyte
      angiography in rabbits.
AB  - PURPOSE: To visualize the retinal and choroidal leukocytes in rabbits with a new
      technique, fluorescein leukocyte angiography using a scanning laser
      ophthalmoscope. METHODS: Blood was withdrawn from an ear vein of a rabbit (New
      Zealand White), mixed with fluorescein dye in a test tube and centrifuged. The
      yellow-brown coat layer containing fluorescein-stained leukocytes was collected
      and injected into the ear vein of the same rabbit while performing fluorescein
      angiography with a scanning laser ophthalmoscope. The angiographic image
      displaying circulating fluorescent leukocytes in retinal and choroidal vessels
      was recorded on a videotape. RESULTS: Fluorescent leukocytes were clearly visible
      in the retinal arteries, capillaries, veins and choroidal vessels for more than 1
      h. Plugging of leukocytes was seen throughout this period of time in choroidal
      vessels, while plugging was rare in retinal vessels. CONCLUSIONS: Fluorescein
      leukocyte angiography is a new technique which can be used for visualization of
      the leukocytes in retinal and choroidal vessels non-invasively and in vivo.

PMID- 9034840
TI  - Collagen gel-embedding culture of conjunctival epithelial cells.
AB  - BACKGROUND: Collagen has effects on cell morphology, differentiation
      characteristics and function. Using collagen gel culture, several studies about
      cell differentiation were reported. In this study, the differentiation of rabbit
      conjunctival epithelial cells in a collagen gel-embedding culture system was
      investigated by electron microscope and lectin labeling. METHODS: Rabbit bulbar
      conjunctival epithelial cells were cultured in type I collagen gel. After 1 and 2
      weeks of culture, some of these cells were stained with PAS and seven kinds of
      lectins, and others were examined by transmission electron microscopy. RESULTS:
      The conjunctival epithelial cells cultured within collagen gel formed stratified
      cell layers and globules with cavities. The inner layer cells facing the cavities
      showed PAS and lectin staining patterns similar to those of conjunctival goblet
      cells in vivo, whereas the staining patterns of the outer layer cells on the
      collagen matrices resembled the patterns of non-goblet epithelial cells.
      Microvilli on the surface of the innermost cells, basement membranes beneath the
      outermost cells, tight junctions, adherent junctions, interdigitating folds and
      desmosomes between cells were identified on electron microscopic examination.
      CONCLUSION: These results indicate that cell junction structures of the
      conjunctival epithelial cells are well developed in collagen gel-embedding
      culture systems, and that the inner layer cells have carbohydrates similar to
      those of conjunctival goblet cells. Culture of conjunctival epithelial cells
      within collagen gel is a useful model for examining differentiation of these
      cells.

PMID- 9034841
TI  - Reattachment to a substrate prevents apoptosis of human retinal pigment
      epithelium.
AB  - BACKGROUND: Epithelial cells generally fail to survive in suspension. Harvesting
      human retinal pigment epithelium (RPE) for transplantation may separate the cells
      from their extracellular matrix and induce apoptosis. We investigated whether
      reattachment of RPE to a substrate will prevent apoptosis. METHODS: Second
      passage human RPE cells were plated onto tissue culture plastic precoated with
      extracellular matrix, fibronectin or laminin, uncoated tissue culture plastic,
      untreated plastic and untreated plastic coated with 4% agarose. Reattachment
      rates were determined for each substrate 24 h after plating. The TUNEL technique
      was used to determine apoptosis rates in attached cells, unattached cells and the
      entire cell population. RESULTS: Attachment rates were as follows: ECM-coated
      tissue culture plastic-->fibronectin-coated tissue culture plastic-->laminin
      coated tissue culture plastic-->uncoated tissue culture plastic-->untreated
      plastic-->agarose-coated untreated plastic. Apoptosis rates for the entire cell
      population increased as the RPE cell attachment rate decreased. The proportion of
      apoptotic cells in the entire population was inversely related to the percent
      attached cells (r = -0.95). CONCLUSION: Reattachment of harvested RPE to a
      substrate decreased the rate of RPE apoptosis in vitro. RPE cells which are
      removed from their substrate prior to transplantation must reattach rapidly to a
      substrate to prevent apoptosis.

PMID- 9034842
TI  - Comparison of tight junction permeability for albumin in iris pigment epithelium
      and retinal pigment epithelium in vitro.
AB  - BACKGROUND: The degenerative retinal diseases are one of the major causes of
      visual loss in the western world. Although heterologous RPE transplants rescue
      the photoreceptors in the dystrophic rat model, rejection remains a major
      limiting factor. Given the common embryonic origin, iris pigment epithelial (IPE)
      cells might be able to take over the functions of retinal pigment epithelial
      (RPE) cells, serving as an autologous graft for transplantation and thereby
      preventing rejection. One of the main functions of RPE cells is the generation of
      tight junctions which form the outer blood-retinal barrier. In this study we
      compared the tight junction permeabilities of IPE and RPE cells isolated from
      Long Evans rats by measuring their albumin clearances. METHODS: IPE and RPE cells
      were cultured on semipermeable filter supports with and without the addition of
      0.02% ethylenediaminetetraacetic acid (EDTA). At selected intervals, the albumin
      clearances of the IPE and RPE cells were measured spectrophotometrically and
      compared. The morphology of the cells was compared using electron microscopy and
      fluorescent labeling. RESULTS: IPE and RPE cells both restricted the passage of
      albumin in vitro. After the modulation of tight junctions with 0.02% EDTA, the
      clearance increased in both types of cells in a similar fashion. The morphology
      of tight junctions was visualized with electron microscopy. CONCLUSION: These
      results indicate that the functional barrier for macromolecules is similar in IPE
      and RPE cells in vitro. This raises the possibility that IPE cells would form
      tight junctions in the subretinal space, thereby substituting for the blood
      retinal barrier normally formed by RPE cells.

PMID- 9034844
TI  - Unusual retinal pigment epitheliopathy and choroidopathy in carcinomatosis: a
      rare case of cancer-associated retinopathy.
AB  - BACKGROUND: Cancer-associated retinopathy is a syndrome causing ocular symptoms.
      It is a rare entity and only a few cases have been reported. METHODS: A 67-year
      old woman with small-cell endometrial carcinoma suffering from deterioration of
      visual acuity is presented. RESULTS: The patient presented with extensive mottled
      changes of the retinal pigment epithelium, accompanied by diffuse subretinal
      fluid in the posterior pole and exudative retinal detachments inferior in both
      eyes. CONCLUSION: This patient suffered from a rare variety of cancer-associated
      retinopathy.

PMID- 9034843
TI  - Scanning laser ophthalmoscope imaging of fluorescein-labelled blood cells.
AB  - PURPOSE: To demonstrate the feasibility of a technique for the visualization by
      scanning laser ophthalmoscope (SLO) of fluorescein-labelled autologous leukocytes
      and platelets in retinal vessels. METHOD: Individual blood samples from rats and
      rabbits were centrifuged to isolate platelets and leukocytes, then passively
      labelled with fluorescein and reinjected into the same animal. An SLO was used to
      visualize and record cell displacement in the retinal circulation. Labelled
      platelets were analysed by flow cytometry. RESULTS: By SLO, platelets appeared as
      a heterogeneous particle flow, and individual leukocytes appearing as brighter
      spots could easily be traced. Flow cytometry showed that after labelling
      platelets were well individualized and their size was slightly increased.
      CONCLUSION: Circulating blood cells can be visualized in retinal vessels by a
      simple method consisting of passive labelling of autologous platelets and
      leukocytes by fluorescein. No platelet toxicity was detected. This method could
      be applied to the study of blood cell movement in human retinal vascular
      diseases.

PMID- 9034845
TI  - Computational models of hippocampal function in memory.

PMID- 9034846
TI  - Distinct memory circuits composing the hippocampal region.
AB  - The very different anatomical designs of the adjacent circuitries of the cortico
      hippocampal pathway, along with their somewhat different synaptic plasticity
      mechanisms, suggest a nearly serial pathway of distinct memory circuits each
      contributing its own specialized processing operation to overall hippocampal
      function. Modeling and formal theoretical analysis of the prominent anatomical
      design features of particular circuits (piriform/entorhinal cortex; hippocampal
      field CA3; hippocampal field CA1) are found to identify potential emergent
      function not readily arrived at in the absence of these formal models, and yet
      which once derived can be seen potentially to confer unique capabilities to an
      integrated hippocampal mechanism for processing memories during behavior.

PMID- 9034847
TI  - A sequence predicting CA3 is a flexible associator that learns and uses context
      to solve hippocampal-like tasks.
AB  - The model discussed in this paper is, by hypothesis, a minimal, biologically
      plausible model of hippocampal region CA3. Because cognitive mapping can be
      viewed as a sequence prediction problem, we qualify this model as a successful
      sequence predictor. Since the model solves problems which require the use of
      context, the model is also able to learn and use context. The model also solves
      configural learning problems of which, at least one, requires a hippocampus.
      Thus, by solving sequence problems, by solving configural learning problems, and
      by creating codes for context, this model provides a computational unification of
      hippocampal functions which are often viewed as disparate.

PMID- 9034848
TI  - Dynamic synapse: a new concept of neural representation and computation.
AB  - Presynaptic mechanisms influencing the probability of neurotransmitter release
      from an axon terminal, such as facilitation, augmentation, and presynaptic
      feedback inhibition, are fundamental features of biological neurons and are
      cardinal physiological properties of synaptic connections in the hippocampus. The
      consequence of these presynaptic mechanisms is that the probability of release
      becomes a function of the temporal pattern of action potential occurrence, and
      hence, the strength of a given synapse varies upon the arrival of each action
      potential invading the terminal region. From the perspective of neural
      information processing, the capability of dynamically tuning the synaptic
      strength as a function of the level of neuronal activation gives rise to a
      significant representational and processing power of temporal spike patterns at
      the synaptic level. Furthermore, there is an exponential growth in such
      computational power when the specific dynamics of presynaptic mechanisms varies
      quantitatively across axon terminals of a single neuron, a recently established
      characteristic of hippocampal synapses. During learning, alterations in the
      presynaptic mechanisms lead to different pattern transformation functions,
      whereas changes in the postsynaptic mechanisms determine how the synaptic signals
      are to be combined. We demonstrate the computational capability of dynamic
      synapses by performing speech recognition from unprocessed, noisy raw waveforms
      of words spoken by multiple speakers with a simple neural network consisting of a
      small number of neurons connected with synapses incorporating dynamically
      determined probability of release. The dynamics included in the model are
      consistent with available experimental data on hippocampal neurons in that
      parameter values were chosen so as to be consistent with time constants of
      facilitative and inhibitory processes governing the dynamics of hippocampal
      synaptic transmission studied using nonlinear systems analytic procedures.

PMID- 9034849
TI  - A theory of hippocampal function in memory.
AB  - First, what is computed by the hippocampus is considered. Based on the effects of
      damage to the hippocampus and neuronal activity recorded in the primate
      hippocampus, it is suggested that it is involved in associating together
      information usually originating from different cortical regions, for example,
      about objects and their place in a spatial environment. The rapid formation of
      such context-dependent memories is prototypical of memories of particular events
      or episodes. Second, a computational theory of how it performs this function,
      based on neuroanatomical and neurophysiological information about the different
      neuronal systems contained within the hippocampus, is described. Key hypotheses
      are that the CA3 pyramidal cells operate as a single autoassociation network to
      store new episodic information as it arrives via a number of specialized
      preprocessing stages from many different association areas of the cerebral
      cortex, and that the dentate granule cell/mossy fiber system is important
      particularly during learning to help to produce a new pattern of firing in the
      CA3 cells for each episode. The computational analysis shows how many memories
      could be stored in the hippocampus, and how quickly the CA3 autoassociation
      system would operate during recall. The analysis is then extended to show how the
      CA3 system could be used to recall the whole of an episodic memory when only a
      fragment of it is presented. It is shown how this retrieval within the
      hippocampus could lead to recall of neuronal activity in association areas of the
      cerebral neocortex similar to that present during the original episode, via
      modified synapses in backprojection pathways from the hippocampus to the cerebral
      neocortex. The recalled information in the cerebral neocortex could then by used
      by the neocortex in the formation of long-term memories and/or in the selection
      of appropriate actions.

PMID- 9034850
TI  - Attention, configuration, and hippocampal function.
AB  - We present a neural network that characterizes a remarkably large number of
      classical conditioning paradigms and describes the effects of many
      neurophysiological manipulations. First, the network 1) describes behavior in
      real time 2) comprises simple and configural stimulus representations, and 3)
      includes attentional control of storage and retrieval. Second, mapping of the
      network onto the brain can be summarized by several information processing loops:
      1) a hippocampal-cortical configural loop, 2) a hippocampal-cerebellar
      conditioned-response loop, 3) a hippocampal-accumbens-thalamic attentional loop,
      and 4) a hippocampal-medial raphe-medial septum error loop. Third, within this
      global view of brain function, it is assumed that the hippocampal formation
      computes 1) the aggregate prediction of environmental events and 2) the error
      signals for cortical learning. These assumptions are supported by rigorous
      computer simulations consistent with a large body of data on hippocampal and
      septal neural activity, induction and blockade of hippocampal long-term
      potentiation, administration of cholinergic agonists and antagonists,
      administration of haloperidol, and selective and nonselective hippocampal and
      cortical lesions.

PMID- 9034851
TI  - Integrating behavioral and physiological models of hippocampal function.
AB  - In recent modeling of hippocampal function, we have attempted to integrate formal
      behavioral analyses of classical conditioning with psychobiological data on brain
      lesions (Gluck and Myers [1993] Hippocampus 3:491-516; Myers and Gluck [1994]
      Behav Neurosci 108(5):835-847). Based on comparative behavioral analyses, we have
      argued that animals with hippocampal region damage are unable to alter stimulus
      similarity based on experience. While hippocampal-damaged animals can still learn
      whether to respond to an individual stimulus, they are notably impaired at many
      tasks involving learning relationships between stimuli-especially in the absence
      of explicit reinforcement. These analyses lead to a computational theory which
      identifies two representational recoding processes-predictive differentiation and
      redundancy compression-which alter stimulus similarity relationships in intact
      animals but are dependent on intact hippocampal region processing. More recent,
      and ongoing, modeling aims to broaden this model of hippocampal region function
      in classical conditioning, with an emphasis on physiological and anatomical
      constraints, including the role of the fornix and subcortical modulation,
      preprocessing in sensory cortices, and localization of the proposed
      representational functions within more precisely identified hippocampal region
      substrates (Myers et al. [1995] Psychology 23(2):116-138; Myers and Gluck [1996]
      Behav Neurosci; Myers et al. [1996] Neurobiol Learning Memory). Working to bridge
      between behavioral and physiological levels of analysis, we ultimately hope to
      develop a more complete understanding of hippocampal region function in memory
      across a wider range of behavioral paradigms, elucidating how this functionality
      emerges from underlying physiological and anatomical substrates.

PMID- 9034852
TI  - Considerations arising from a complementary learning systems perspective on
      hippocampus and neocortex.
AB  - We discuss a framework for the organization of learning systems in the mammalian
      brain, in which the hippocampus and related areas form a memory system
      complementary to learning mechanisms in neocortex and other areas. The
      hippocampal system stores new episodes and "replays" them to the neocortical
      system, interleaved with ongoing experience, allowing generalization as cortical
      memories form. The data to account for include: 1) neurophysiological findings
      concerning representations in hippocampal areas, 2) behavioral evidence
      demonstrating a spatial role for hippocampus, 3) and effects of surgical and
      pharmacological manipulations on neuronal firing in hippocampal regions in
      behaving animals. We hypothesize that the hippocampal memory system consists of
      three major modules: 1) an invertible encoder subsystem supported by the pathways
      between neocortex and entorhinal cortex, which provides a stable, compressed,
      invertible encoding in entorhinal cortex (EC) of cortical activity patterns, 2) a
      memory separation, storage, and retrieval subsystem, supported by pathways
      between EC, dentate gyrus and area CA3, including the CA3 recurrent collaterals,
      which facilitates encoding and storage in CA3 of individual EC patterns, and
      retrieval of those CA3 encodings, in a manner that minimizes interference, and 3)
      a memory decoding subsystem, supported by the Shaffer collaterals from area CA1
      to area CA3 and the bi-directional pathways between EC and CA3, which provides
      the means by which a retrieved CA3 coding of an EC pattern can reinstate that
      pattern on EC. This model has shown that 1) there is a trade-off between the need
      for information-preserving, structure-extracting encoding of cortical traces and
      the need for effective storage and recall of arbitrary traces, 2) long-term
      depression of synaptic strength in the pathways subject to long-term potentiation
      is crucial in preserving information, 3) area CA1 must be able to exploit
      correlations in EC patterns in the direct perforant path synapses.

PMID- 9034853
TI  - How much of the hippocampus can be explained by functional constraints?
AB  - In the spirit of Marr, we discuss an information-theoretic approach that derives,
      from the role of the hippocampus in memory, constraints on its anatomical and
      physiological structure. The observed structure is consistent with such
      constraints, and, further, we relate the quantitative arguments developed in
      earlier analytical studies to experimental measures extracted from neuronal
      recordings in the behaving rat.

PMID- 9034854
TI  - TraceLink: a model of amnesia and consolidation of memory.
AB  - A model of amnesia is introduced, called TraceLink, that consists of three
      systems: 1) a trace system (neocortex), 2) a link system (hippocampus), and 3) a
      modulatory system (hippocampus/fornix/basal forebrain). It aims to explain
      salient aspects of the neuropsychology of amnesia, such as Ribot gradients in
      retrograde amnesia, patterns of dissociation between anterograde and retrograde
      amnesia, recovery from amnesia, and a newly discovered form of amnesia (semantic
      dementia) that results from certain temporal lobe lesions that do not affect the
      hippocampus. The model, furthermore, offers a new explanation for the global
      neuroanatomy of the hippocampus and neocortex based on the assumption that the
      brain aims to minimize connectivity volume. It also offers various strategies for
      the consolidation of memory, the effects of which are explored in computer
      simulations. The paper concludes with ten, largely untested; predictions derived
      from the TraceLink model.

PMID- 9034855
TI  - Modeling the spontaneous reactivation of experience-specific hippocampal cell
      assembles during sleep.
AB  - During slow-wave sleep (SWS) following periods of spatial activity, hippocampal
      place cells that were temporally correlated, by virtue of the overlap of their
      place fields, exhibit enhanced temporal correlations, even though the animal
      sleeps in a different location (Wilson and McNaughton [1994] Science 267:676
      679). The discharge of cells with overlapped place fields is more correlated in
      subsequent sleep, particularly during sharp waves, than in sleep episodes prior
      to the behavior, or than cell pairs with non-overlapped place fields. The
      reactivated correlated states appear during hippocampal sharp waves (SPWs), and
      are weak or absent in the inter-SPW interval. A simple conceptual hypothesis for
      this phenomenon is developed, based on the idea that hippocampal place fields
      reflect a two-dimensional distribution of continuously overlapping dynamic
      attractors in which each location is represented by the self-sustaining activity
      of a small subset of neurons with overlapping place fields. A numerical
      simulation of this hypothesis, based on a simplified representation of the CA8
      recurrent network, accounts qualitatively for the main observations, including
      SPW-like dynamics. It is shown that, under conditions in which the connection
      patterns have been previously established, either associative or nonassociative
      mechanisms might underlie the reactivation of recently experienced states. These
      two alternatives appear, under at least some conditions (e.g., sparse coding), to
      be indistinguishable.

PMID- 9034856
TI  - Encoding and retrieval of episodic memories: role of cholinergic and GABAergic
      modulation in the hippocampus.
AB  - This research focuses on linking episodic memory function to the cellular
      physiology of hippocampal neurons, with a particular emphasis on modulatory
      effects at cholinergic and gamma-aminobutyric acid B receptors. Drugs which block
      acetylcholine receptors (e.g., scopolamine) have been shown to impair encoding of
      new information in humans, nonhuman primates, and rodents. Extensive data have
      been gathered about the cellular effects of acetylcholine in the hippocampus. In
      this research, models of individual hippocampal subregions have been utilized to
      understand the significance of particular features of modulation, and these
      hippocampal subregions have been combined in a network simulation which can
      replicate the selective encoding impairment produced by scopolamine in human
      subjects.

PMID- 9034857
TI  - Hippocampal place cells connected by Hebbian synapses can solve spatial problems.
AB  - We propose that a cognitive map can be stored in the synapses between the
      pyramidal cells of CA3 in the form of the pattern of synaptic strengths
      connecting them. The model requires only that there are place cells in CA3 and
      that the connections between them are modifiable in a Hebbian manner. Given these
      suppositions, the synaptic strengths must evolve to represent the distance
      between firing centers of synaptically connected place cells. We argue that this
      arrangement of synaptic weights embodies all the formal properties of a map. We
      demonstrate that the information stored in such a structure is sufficient to
      solve several classic spatial problems including finding shortest paths, and
      negotiating detours. It is clear that much of the physiology and anatomy
      necessary to more precisely characterize the model is not known at this time.
      Nevertheless the model is robust under a variety of cell and connection
      densities. It also performs well under several different functions relating
      distance to synaptic strength. What is most remarkable in the model is that it is
      a logical consequence of the several key anatomical and physiological properties
      of the CA3 region of rats. Whether this information is used by the rat is
      difficult to assess at this time. Regardless of the outcome of this question, the
      model has promising applications to the field of robot navigation.

PMID- 9034859
TI  - Memory for places: a navigational model in support of Marr's theory of
      hippocampal function.
AB  - In this report we describe a model that applies Marr's theory of hippocampal
      function to the problem of map-based navigation. Like many others we attribute a
      spatial memory function to the hippocampus, but we suggest that the additional
      functional components required for map-based navigation are located elsewhere in
      the brain. One of the key functional components in this model is an egocentric
      map of space, located in the neocortex, that is continuously updated using
      ideothetic (self-motion) information. The hippocampus stores snapshots of this
      egocentric map. The modeled activity pattern of head direction cells is used to
      set the best egocentric map rotation to match the snapshots stored in the
      hippocampus, resulting in place cells with a nondirectional firing pattern. We
      describe an evaluation of this model using a mobile robot and demonstrate that
      with this model the robot can recognize an environment and find a hidden goal.
      This model is discussed in the context of prior experiments that were designed to
      discover the map-based spatial processing of animals. We also predict the results
      of further experiments.

PMID- 9034858
TI  - Neural network modeling of the hippocampal formation spatial signals and their
      possible role in navigation: a modular approach.
AB  - Cells throughout the hippocampal formation show striking spatial firing
      correlates as a rat navigates through space. These cells are thought to play a
      critical role in orchestrating the navigational abilities of the animals, since
      damage to the hippocampal formation causes spatial learning deficits. Here, we
      present a theoretical framework aimed at explaining how the different spatial
      signals are generated, as well as how they may help guide navigational behavior.
      Earlier work from our laboratory has presented a simple model for how the
      location-related signals exhibited by hippocampal place cells could be generated,
      based on convergent sensory information. Here, the results of this work are
      combined with two more recent models, to provide a more comprehensive theoretical
      framework. Specifically, we present 1) A neural network model of head direction
      cells, based on the idea that the directional signals are generated using a path
      integration mechanism. Cells which combine directional and angular head velocity
      information project onto the head direction cells, to "update" the current
      directional signal. This model reproduces the basic phenomenon of direction
      specific firing, as well as the anticipatory nature of this firing, reported for
      some head direction cells. 2) A network simulation of how the hippocampal spatial
      signals could be used to orchestrate instrumental learning. Here, place and
      directional signals converge onto motor cells, each of which are thus driven to
      fire to specific combinations of location and directional heading. Each active
      motor cell generates a small leftward or rightward "step" of the simulated
      animal. When the simulated goal is encountered, recently active synapses are
      strengthened, so that goal-directed trajectories are "stamped in". We have found
      these models useful in helping to clarify our thinking about the proposed
      theoretical principles, as well as in generating testable predictions.

PMID- 9034860
TI  - Neuronal computations underlying the firing of place cells and their role in
      navigation.
AB  - Our model of the spatial and temporal aspects of place cell firing and their role
      in rat navigation is reviewed. The model provides a candidate mechanism, at the
      level of individual cells, by which place cell information concerning self
      localization could be used to guide navigation to previously visited reward
      sites. The model embodies specific predictions regarding the formation of place
      fields, the phase coding of place cell firing with respect to the hippocampal
      theta rhythm, and the formation of neuronal population vectors downstream from
      the place cells that code for the directions of goals during navigation. Recent
      experiments regarding the spatial distribution of place cell firing have
      confirmed our initial modeling hypothesis, that place fields are formed from
      Gaussian tuning curve inputs coding for the distances from environmental
      features, and enabled us to further specify the functional form of these inputs.
      Other recent experiments regarding the temporal distribution of place cell firing
      in two-dimensional environments have confirmed our predictions based on the
      temporal aspects of place cell firing on linear tracks. Directions for further
      experiments and refinements to the model are outlined for the future.

PMID- 9034861
TI  - Synthetic peptides derived from human MHC class I sequences delay allograft
      rejection in rodents and inhibit cell-mediated cytotoxicity in vivo and in vitro.

PMID- 9034862
TI  - The role of polymorphic donor peptides in allograft recognition and rejection.

PMID- 9034863
TI  - The role of peptide specificity in MHC class I-restricted allogeneic responses.

PMID- 9034864
TI  - Alloreactivity, antigen recognition and T-cell selection: three diverse T-cell
      recognition problems with a common solution.

PMID- 9034865
TI  - The HLA likes and dislikes of allospecific and non-MHC-restricted cytotoxic T
      lymphocytes.

PMID- 9034866
TI  - Presentation of HLA class I-derived peptides: potential involvement in
      allorecognition and HLA-B27-associated arthritis.
AB  - Some 25 years ago, when purified HLA class I allotypes were first being analyzed,
      of major concern was that the papain used for solubilization might produce a mess
      of proteolytic fragments that would prove impossible to separate and sequence.
      Those fears proved unfounded (Parham et al. 1975), and the homogeneity of the
      preparations was sufficient to allow crystallization and determination of the
      three-dimensional structure (Bjorkman et al. 1987). Ironically the least ordered
      region of the electron density map provoked the most interest because it gave a
      first view of the diverse peptides bound by an MHC molecule. With this image a
      second chapter of HLA class I biochemistry began, its charge to determine the
      structures of bound peptides and their influence on the immune system. The
      extraordinary polymorphism of HLA class I heavy chains now seems quite manageable
      compared to the vast complexity of the peptides, and our present ignorance as to
      which ones are important for health and disease. The comparative weakness of most
      HLA class I associations with disease has made HLA-B27 an especially favored
      target for investigation, and more is known of the structure and peptide
      presenting function of HLA-B27 than for any other HLA-B allotype (Lopez de Castro
      1994). Much of this information relates to the native HLA-B27 molecule and has
      been collected in the belief that disease is a direct consequence of its antigen
      presenting function. If one subscribes to the relevance of the transgenic rodent
      models, this position has almost become untenable. For rats and mice 'non
      functional' forms of HLA-B27 are the agents of disease, raising the possibility
      that B27-associated arthritis is induced by HLA class II presentation of a B27
      derived peptide, a variant of the mechanism advanced for the classical HLA class
      II-associated diseases: type 1 diabetes, multiple sclerosis and rheumatoid
      arthritis (Gregersen et al. 1987, Roudier et al. 1989, Cucca & Todd 1996, Hall &
      Bowness 1996). Such speculation invites the obvious question as to whether other
      diseases associated with HLA class I and chronic inflammation, HLA-C and
      psoriasis for example (Tiilikainen et al. 1980, Yanagisawa et al. 1995), result
      from class II presentation of class I peptides.

PMID- 9034867
TI  - The role of endogenous peptides in the direct pathway of alloreactivity to human
      MHC class II molecules expressed on CHO cells.

PMID- 9034868
TI  - Superantigens in autoimmune diseases: still more shades of gray.

PMID- 9034875
TI  - Developing an international nursing partnership with Nicaragua.
AB  - With health conditions in the "least developed countries persisting at levels
      that are so limiting and destructive of human potential ... as to be unacceptable
      to the global community", WHO has put out a call for mandates to address these
      problems with "new approaches ... new partnerships." One answer to this call has
      come from the US' Duquesne University School of Nursing, which has founded an
      education and service partnership with Nicaragua that can serve as a "grass
      roots" model others can follow.

PMID- 9034876
TI  - Future directions in transcultural nursing in the 21st century.
AB  - With the inevitable trend towards TCN, all nursing education, research and
      practice will of necessity become transculturally based, hopefully by the year
      2020 or earlier. Meanwhile, an incredible amount of TCN leadership is needed to
      adequately prepare nurses to function in our growingly academically prepared to
      teach TCN and to practice in a culturally competent way. Nursing service and
      other major organizations need to become transcultural institutions.
      Communication with nurses from countries everywhere echo nurses' eagerness to
      prepare themselves in transcultural nursing, especially those frustrated in the
      caring of immigrants and people of diverse cultures.

PMID- 9034877
TI  - Community-based nursing education: a five-stage process.
AB  - Confronted with changing healthcare systems, nursing educators must now visualize
      nursing and nursing education from a different perspective. Students must be
      prepared to meet the needs of populations rather than institutions and form new
      partnerships in the community if they are to be prepared for health care in the
      next century. This makes communication between academia and community clinical
      settings essential. It is by restructuring nursing education that graduates will
      be prepared to function in the 21st century. Nursing faculty believe the
      community clinical experiences contribute to the preparation of baccalaureate
      nursing students for anticipated healthcare reform. The creative key to
      successful clinical experience is collaboration of learning strategies and
      experience that empowers students to expand and discover new paradigms and
      therefore elevate the profession.

PMID- 9034878
TI  - Glial-glial and glial-neuronal interfaces in radiation-induced, glia-depleted
      spinal cord.
AB  - This review summarises some of the major findings derived from studies using the
      model of a glia-depleted environment developed and characterised in this
      laboratory. Glial depletion is achieved by exposure of the immature rodent spinal
      cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte
      populations and severely impairs myelination. This glia-depleted, hypomyelinated
      state presents a unique opportunity to examine aspects of spinal cord maturation
      in the absence of a normal glial population. An associated sequela within 2-3 wk
      following irradiation is the appearance of Schwann cells in the dorsal portion of
      the spinal cord. Characteristics of these intraspinal Schwann cells, their
      patterns of myelination or ensheathment, and their interrelations with the few
      remaining central glia have been examined. A later sequela is the development of
      Schwann cells in the ventral aspect of the spinal cord where they occur
      predominantly in the grey matter. Characteristics of these ventrally situated
      intraspinal Schwann cells are compared with those of Schwann cells located
      dorsally. Recently, injury responses have been defined in the glia-depleted
      spinal cord subsequent to the lesioning of dorsal spinal nerve roots. In
      otherwise normal animals, dorsal nerve root injury induces an astrocytic reaction
      within the spinal segments with which the root(s) is/are associated. Lesioning of
      the 4th lumbar dorsal root on the right side in irradiated or nonirradiated
      animals results in markedly different glial responses with little astrocytic
      scarring in the irradiated animals. Tracing studies reveal that these lesioned
      dorsal root axons regrow rather robustly into the spinal cord in irradiated but
      not in nonirradiated animals. To examine role(s) of glial cells in preventing
      this axonal regrowth, glial cells are now being added back to this glia-depleted
      environment through transplantation of cultured glia into the irradiated area.
      Transplanted astrocytes establish barrier-like arrangements within the irradiated
      cords and prevent axonal regrowth into the cord. Studies using other types of
      glial cultures (oligodendrocyte or mixed) are ongoing.

PMID- 9034879
TI  - Transplanting oligodendrocyte progenitors into the adult CNS.
AB  - This review covers a number of aspects of the behaviour of oligodendrocyte
      progenitors following transplantation into the adult CNS. First, an account is
      given of the ability of transplanted oligodendrocyte progenitors, grown in tissue
      culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas
      of persistent demyelination. Secondly, we describe how transplanted clonal cell
      lines of oligodendrocyte progenitors will differentiate into astrocytes as well
      oligodendrocytes following transplantation into pathological environments in
      which both oligodendrocytes and astrocytes are absent, thereby manifesting the
      bipotentially demonstrable in vitro but not during development. Finally, a series
      of studies examining the migratory behaviour of transplanted oligodendrocyte
      progenitors (modelled using the oliodendrocyte progenitor cell line CG4) are
      described. These show that CG4 cells do not survive (or migrate) when
      transplanted into the normal adult CNS. However, if they are transplanted into
      CNS tissue that has previously been exposed to 40 Gy of x-irradiation then
      transplanted CG4 cells survive, divide and migrate over large distances.
      Moreover, within an x-irradiated environment, migrating transplanted CG4 cells
      are able to enter remotely located foci of demyelination and contribute to the
      remyelination of the demyelinated axons within. These studies demonstrate that
      although the normal adult CNS does not appear to support survival and migration
      of the CG4 cell line, it is possible to manipulate the environment in such a way
      that these nonpermissive properties of the environment can be overcome.

PMID- 9034880
TI  - Schwann cell invasion of the central nervous system of the myelin mutants.
AB  - Schwann cells are excluded from the CNS during development by the glial limiting
      membrane, an area of astrocytic specialisation present at the nerve root
      transitional zone, and at blood vessels in the neuropil. This barrier, however,
      can be disrupted and, with the highly migratory nature of Schwann cells, can
      result in their invasion and myelination of the CNS in many pathological
      situations. In this paper we demonstrate that this occurs in a number of myelin
      mutants, including the myelin deficient (md) and taiep rats and the canine
      shaking (sh) pup. While it is still relatively uncommon in the rodent mutants,
      the sh pup shows extensive Schwann cell invasion along the neuraxis. This
      invasion involves the spinal cord, brain stem, and cerebellum and increases in
      amount and distribution with age. In situ hybridisation studies using a Pzero
      riboprobe suggest that the likely origin of these cells in the sh pup is the
      nerve roots, primarily the dorsal roots. Paradoxically, Schwann cell myelination
      of the CNS increases with time in the sh pup despite a marked, progressive
      gliosis involving the glia limitans and neuropil. Thus the mechanism by which
      these cells migrate into the CNS through the gliosed nerve root transitional zone
      or from vasa nervorum remains unknown. Extensive Schwann cell CNS myelination may
      have therapeutic significance in human myelin disease.

PMID- 9034883
TI  - Use of antibodies directed against blood group substances and lectins together
      with glycosidase digestion to study the composition and cellular distribution of
      glycoproteins in the large human airways.
AB  - Some 30 lectins in combination with glycosidase digestion and
      immunohistochemistry with 5 antibodies directed against antigens of the ABO and
      Lewis blood group systems were used to analyse the distribution and synthesis of
      glycoconjugates in the epithelium of the large airways in man. Both mucous gland
      cells and goblet cells were labelled by 12 of 30 lectins and by the antibodies,
      dependent on the ABO, Lewis, and secretor status. The corresponding binding
      patterns of the serous gland cells differed markedly from those of goblet and
      mucous gland cells and in general were not dependent on the ABO, Lewis, and
      secretor status. After digestion with neuraminidase and fucosidase, binding of
      soy bean agglutinin and peanut agglutinin to goblet and mucous gland cells was
      increased. Binding of peanut agglutinin to serous gland cells was stronger only
      after the digestion with neuraminidase. Digestion with O-glycosidase after the
      use of neuraminidase or fucosidase resulted in a decrease of peanut agglutinin
      binding to goblet and mucous gland cells. The present results show that the
      secretory products of goblet and mucous gland cells on the one hand and those of
      serous cells on the other differ considerably with respect to their terminal
      glycosylation. The glycosyltransferases coded by genes of the ABO and Lewis blood
      group and secretor systems are active only in goblet and mucous gland cells,
      resulting in the presence of the corresponding antigens. Precursor substances of
      blood group antigens types 1, 2, and 3 are found only in these cell types. In
      serous gland cells, blood group systems do not influence the glycosylation of
      glycoproteins. The results of the digestion with O-glycosidase indicates the
      presence of O-glycosylation in mucous gland and goblet cells, but not in serous
      gland cells.

PMID- 9034882
TI  - Axonal regeneration through acellular muscle grafts.
AB  - The management of peripheral nerve injury remains a major clinical problem.
      Progress in this field will almost certainly depend upon manipulating the
      pathophysiological processes which are triggered by traumatic injuries. One of
      the most important determinants of functional outcome after the reconstruction of
      a transected peripheral nerve is the length of the gap between proximal and
      distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit
      in order to support axonal regrowth. This review examines the cellular and
      acellular elements which facilitate axonal regrowth and the use of acellular
      muscle grafts in the repair of injuries in the peripheral nervous system.

PMID- 9034881
TI  - Nerve fibre regeneration across the peripheral-central transitional zone.
AB  - Neurons cannot negotiate an elongation across the peripheral (PNS)-central
      nervous system (CNS) transitional zone and grow into or out of the spinal cord in
      the mature mammal. The astrocytic rich CNS part of the spinal nerve root is most
      effective in preventing regeneration even of nerve fibres from transplanted
      embryonic ganglion cells. Regeneration of severed nerve fibres into the spinal
      cord occurs when the transition zone is absent as in the immature animal. Before
      the establishment of a transition zone there is also new growth of neuronal
      processes from dorsal horn neurons distally to the injured dorsal root. Thus the
      experimental strategy to reestablish spinal cord to peripheral nerve connectivity
      has been to delete the transitional region and implant severed ventral or dorsal
      roots into the spinal cord. Dorsal root implantation resulted in reestablished
      afferent connectivity by new neuronal processes from secondary sensory neurons in
      the dorsal horn of the spinal cord extending into the PNS. The ability for
      plasticity in these cells allowed for a concurrent retention of their original
      rostral projection. Ventral root implantation into the spinal cord corrected
      deficit motor function. In a long series of experiments performed in different
      species, the functional restitution was demonstrated to depend on an initial
      regrowth of motor neuron axons through spinal cord tissue (CNS). These findings
      have led to the design of a new surgical strategy in cases of traumatic spinal
      nerve root injuries.

PMID- 9034884
TI  - Stromal cell organisation in the mouse lymph node. A light and electron
      microscopic investigation using the zinc iodide-osmium technique.
AB  - The organisation of the stromal cell compartment in the mouse lymph node was
      studied by light and electron microscopy after tissue impregnation by the zinc
      iodide-osmium (ZIO) method. Fibroblastic reticular cells (FRCs) represented the
      main stromal cell population. These cells were located both in the cortical
      region and in the medulla and exhibited various configurations. In the cortex,
      FRCs were fusiform in shape and came into close proximity with the floor of the
      subcapsular sinus. In the medulla, the FRCs were shaped like irregular dendritic
      cells which formed a complex 3-dimensional network. The FRCs surrounded vascular
      structures such as capillaries and/or high endothelial venules; in these
      instances they were organised in a discontinuous sheath-like fashion around the
      vessel wall. By light and electron microscopy, FRCs have been observed to come in
      close spatial relationship with a number of cells in the lymph node, including
      sinus endothelial cells, the endothelium of high endothelial venules and
      capillaries, various types of lymphocytes, follicular dendritic cells and
      interdigitating cells. These microanatomical features are consistent with the
      proposal that FRCs may be involved in the communicative networks between the
      different lymph node compartments. In particular, the FRCs may be involved in the
      transport of molecules from the sinus compartment to the high endothelial venules
      or to the distinct cell populations in the lymphoid parenchyma.

PMID- 9034886
TI  - Adaptation in the vertebral column: a comparative study of patterns of metameric
      variation in mice and men.
AB  - In this paper we examine metamerism in the vertebral column of certain mammals
      from the perspectives of development and adaptation. To this end we examine the
      patterns of metameric variation of dimensions of the neural (vertebral) canal,
      vertebral body and spinous process in man and inbred strains of mice. The data
      from inbred strains of mice indicate that variability in dimensions within a
      strain reflects the temporal ordering and nature of developmental influences on
      vertebral morphogenesis. Differences between strains parallel the within-strain
      findings. These findings are attributed to somatic and neural influences on
      morphogenesis. Comparisons between mice and man indicate that these same
      influences can be invoked to explain and interpret the mosaic nature of vertebral
      column evolution. These findings lead us to conclude that different vertebral
      elements and levels are subject to different interactions of evolutionary and
      morphogenetic influences. The study of these influences and their interactions
      should prove fruitful in developing an understanding of the relationship between
      adaptation, development, growth and function in the skeleton generally.

PMID- 9034887
TI  - The hypogastric and thirteenth thoracic ganglia of the rat: effects of age on the
      neurons and their extracellular environment.
AB  - Morphometric analyses of the neurons and microvessels of perfusion-fixed
      hypogastric (HG) and 13th thoracic (T13) ganglia have been performed in male
      Wistar rats aged 4, 24 and 30 mo. Estimations of HG volume employing the
      Cavalieri principle have also been performed and showed that the size of the aged
      HG is increased by 42%. Routine histological staining of the ganglia with
      Masson's trichrome indicated that this may be due to the increased amount of
      interstitial connective tissue which was apparent in the aged animals. The number
      of neurons per unit area progressively decreased by 38% between ages 4 and 24 mo
      and by 16% between ages 24 and 30 mo in the HG and by 25% (4 and 24 mo) and 2%
      (24 and 30 mo) in the T13 ganglion. The total number of neurons in the HG
      however, estimated by a physical disector analysis, was constant with age. The
      number of microvessels per unit area, microvessel diameter, neuronal and nuclear
      areas did not differ significantly between the 3 age groups studied. This
      observed increase in ganglionic volume and decrease in neuronal packing density
      may be associated with changes in the extracellular matrix, in particular in
      glycosaminoglycans whose presence was indicated by metachromasia of the ganglia
      with toluidine blue. The extracellular matrix was therefore characterised using a
      panel of monoclonal antibodies against glycosaminoglycans and laminin.
      Chondroitin-6 sulphate and chondroitin-4 sulphate were present in the
      interstitial connective tissue, and there was an increase in the expression of
      both these epitopes at 24 mo, noteably surrounding neuron cell bodies. The
      expression of chondroitin-4 sulphate/dermatan sulphate was unchanged, thus
      implying a decreased expression of dermatan sulphate with age. Keratan sulphate
      and the native chondroitin sulphate epitopes were absent from the ganglia at both
      ages. Laminin expression was increased in the aged ganglia. It is therefore clear
      that the constituents of the extracellular matrix are not constant throughout the
      adult lifespan and that the extracellular matrix may influence neuronal survival
      in old age. This is the first report characterising age-related changes in the
      extracellular matrix of autonomic ganglia.

PMID- 9034885
TI  - Ultrastructural localisation of nitric oxide synthase, endothelin and binding
      sites of lectin (from Bandeirea simplicifolia) in the rat carotid artery after
      balloon catheter injury.
AB  - An immunocytochemical and cytochemical study has been made on the ultrastructural
      localisation of type III (endothelial) nitric oxide synthase, endothelin-1 and
      the binding sites of lectin from Bandeirea simplicifolia to the endothelium
      surface-associated glycoproteins in the rat left common carotid artery at 1 and
      28 d after Fogarty embolectomy balloon catheter-induced injury. Controls were
      carotid arteries from sham operated rats. In the controls, the immunoreactivity
      to nitric oxide synthase-III and endothelin-1 was localised in different
      proportions in vascular endothelial cells (36.9% +/- 4.3 and 7.6% +/- 2.7,
      respectively); immunoreactivity was confined to the cytoplasm and the membranes
      of intracellular organelles and structures. In contrast, staining with lectin was
      localised on the luminal surface of all endothelial cells. 1 d after injury,
      platelets were adherent to the endothelium-denuded intima. Some of the platelets
      displayed, immunoreactivity to nitric oxide synthase-III and endothelin-1 and
      were stained with lectin. 28 d after injury, a neointimal thickening of
      substantial size was present. Subpopulations of the regrown endothelial cells
      covering the luminal surface of the neointima showed positive immunoreactivity to
      nitric oxide synthase-III and endothelin-1 but there was a significant decrease
      in the proportion of nitric oxide synthase-III-containing endothelial cells
      (17.2% +/- 1.9; P < 0.001) and a significant increase in the proportion of
      endothelin-1-containing endothelial cells (36.9% +/- 4.7; P < 0.001) compared
      with the controls. Staining with lectin was associated with the cell membrane of
      all endothelial cells and in addition with cells located 'deeper' in the
      neointima which showed lectin-positive plasmalemma, Golgi complex and
      multivesicular bodies/lysosomes. In conclusion, regenerated endothelial cells of
      the neointima showed reduced population (2-fold) of nitric oxide synthase-III-and
      increased population (5-fold) endothelin-1-positive cells. The subendothelial
      location of some lectin-stained cells after balloon catheter injury indicates the
      heterogeneity of the neointima and suggests that some of these cells are involved
      in early angiogenesis. 24 h and 28 d after injury some platelets showed positive
      immunoreactivity for nitric oxide synthase-III and endothelin-1.

PMID- 9034888
TI  - A double-label immunohistochemical study of intramural ganglia from the human
      male urinary bladder neck.
AB  - Double-label immunocytochemistry was used to investigate the colocalisation of
      various neuropeptides and the enzymes nitric oxide synthase (NOS) and tyrosine
      hydroxylase (TH) in intramural ganglia of the human male urinary bladder neck and
      trigone. Postmortem specimens were obtained from 7 male infants and children
      ranging in age from 2 mo to 3 y who had died as a result of cot death or
      accidental trauma. On average 60% of the intramural neurons were non-TH
      immunoreactive (-IR) (i.e. presumptive cholinergic) and 40% were TH- and D beta H
      IR (i.e. noradrenergic). Within the non-TH-IR population, calcitonin gene-related
      peptide (CGRP) was found in 65% of cells, neuropeptide Y (NPY) in 90%, nitric
      oxide synthase (NOS) in 45%, somatostatin (SOM) in 90%, and vasoactive intestinal
      polypeptide (VIP) in 40%. The corresponding values for the TH-IR neurons were
      CGRP (54%), NPY (70%), NOS (58%), SOM (73%) and VIP (40%). All the observed
      bombesin (BOM)-immunoreactivity was colocalised with TH while 90% of VIP and
      almost all the CGRP was colocalised with NPY. Less than 5% of neurons were
      immunoreactive for substance P (SP) or met-enkephalin (m-ENK) and some of these
      also contained TH. Varicose nerve fibres were seen in close proximity to some of
      the intramural neurons, the majority of such varicosities showing
      immunoreactivity to CGRP, VIP or TH. Less common were pericellular varicosities
      immunoreactive to NPY, SOM or SP. These results demonstrate the neurochemical
      heterogeneity of intramural neurons in the human bladder neck and provide
      indirect evidence for the complexity of the peripheral innervation of the human
      urinary bladder.

PMID- 9034889
TI  - Distribution of NADPH-diaphorase and nitric oxide synthase-containing neurons in
      the intramural ganglia of guinea pig urinary bladder.
AB  - The cell population and distribution of NADPH-diaphorase positive and NOS
      immunoreactive intramural ganglion cells were examined on stretched whole-mount
      preparations of the guinea pig urinary bladder which was divided into 3 regions:
      base, body and dome. The results showed that the highest frequency both of NADPH
      d and NOS positive neurons was observed in the bladder base. Cell counts in the
      whole bladder showed that the number of NADPH-d positive neurons was much more
      than that of NOS immunoreactive neurons. Using neuron specific enolase (NSE)
      positive neurons as a reference (100%), NADPH-d positive neurons accounted for
      84% while NOS immunoreactive neurons only made up 45% of the total neuronal
      population. These results, along with previous studies on the function of nitric
      oxide, suggest that nitric oxide may be involved in the relaxation activity in
      the bladder base during micturition. The significant difference in the number of
      NADPH-d positive and NOS immunoreactive neurons suggests that the localisation of
      one enzyme does not necessarily reflect the presence of the other.

PMID- 9034890
TI  - Communication between the superior cervical sympathetic ganglion and the inferior
      laryngeal nerve.

PMID- 9034891
TI  - World Wide Web access to the British Universities Human Embryo Database.

PMID- 9034892
TI  - Case report: congenital urethrocutaneous fistula.

PMID- 9034893
TI  - Synaptic connections between identified neuron types in the antennal lobe
      glomeruli of the cockroach, Periplaneta americana: I. Uniglomerular projection
      neurons.
AB  - A combination of three different labels was used to demonstrate synapses between
      three types of neurons within the glomeruli: 1) antennal receptor cells, 2) gamma
      aminobutyric acid (GABA)-immunoreactive neurons, and 3) uniglomerular projection
      neurons. Receptor cell axons were experimentally severed and caused to
      degenerate; uniglomerular projection neurons, a subgroup of glomerular output
      neurons, were labeled by intracellular horseradish peroxidase (HRP) injection and
      GABA-containing neurons by postembedding immunogold staining. The following
      synaptic connections were identified: 1) Receptor cell axons form monosynaptic
      contacts in a dyadic fashion onto a dendritic process of a uniglomerular
      projection neuron and in addition onto a GABA-immunoreactive neuron. 2) Receptor
      cell axons form polysynaptic connections with dendrites of uniglomerular
      projection neurons via GABA-immunoreactive neurons. 3) GABA-immunoreactive
      neurons form dyadic output synapses onto receptor cell axons and in addition onto
      projection neuron dendrites. These findings provide further evidence that signal
      transfer from receptor cells onto uniglomerular projection neurons is mediated by
      two different paths: first, a monosynaptic and presumably excitatory route and,
      second, an inhibitory polysynaptic route via GABAergic, most likely
      multiglomerular interneurons. The output synapses of GABA-immunoreactive neurons
      onto both receptor cells and uniglomerular projection neurons are assumed to
      exert control functions in regulating the neuronal activity within the glomeruli.

PMID- 9034894
TI  - Immunostaining for substance P receptor labels GABAergic cells with distinct
      termination patterns in the hippocampus.
AB  - A specific antiserum against substance P receptor (SPR) labels nonprincipal
      neurons in the cerebral cortex of the rat (T. Kaneko et al. [1994], Neuroscience
      60:199-211; Y. Nakaya et al. [1994], J. Comp. Neurol. 347:249-274). In the
      present study, we aimed to identify the types of SPR-immunoreactive neurons in
      the hippocampus according to their content of neurochemical markers, which label
      interneuron populations with distinct termination patterns. Markers for
      perisomatic inhibitory cells, parvalbumin and cholecystokinin (CCK), colocalized
      with SPR in pyramidallike basket cells in the dentate gyrus and in large
      multipolar or bitufted cells within all hippocampal subfields respectively. A
      dense meshwork of SPR-immunoreactive spiny dendrites in the hilus and stratum
      lucidum of the CA3 region belonged largely to inhibitory cells terminating in the
      distal dendritic region of granule cells, as indicated by the somatostatin and
      neuropeptide Y (NPY) content. In addition, SPR and NPY were colocalized in
      numerous multipolar interneurons with dendrites branching close to the soma.
      Twenty-five percent of the SPR-immunoreactive cells overlapped with calretinin
      positive neurons in all hippocampal subfields, showing that interneurons
      specialized to contact other gamma-aminobutyric acid-ergic cells may also contain
      SPR. On the basis of the known termination pattern of the colocalized markers, we
      conclude that SPR-positive interneurons are functionally heterogeneous and
      participate in different inhibitory processes: (1) perisomatic inhibition of
      principal cells (CCK-containing cells, and parvalbumin-positive cells in the
      dentate gyrus), (2) feedback dendritic inhibition in the entorhinal termination
      zone (somatostatin and NPY-containing cells), and (3) innervation of other
      interneurons (calretinin-containing cells).

PMID- 9034895
TI  - Organization of somatosensory cortex and distribution of corticospinal neurons in
      the eastern mole (Scalopus aquaticus).
AB  - The somatotopic organization of somatosensory cortex of the eastern mole
      (Scalopus aquaticus) was explored with multiunit microelectrode recordings from
      middle layers of cortex. The recordings revealed the presence of at least parts
      of two systematic representations of the body surface in the lateral cortex. One
      of the representations appears to be primary somatosensory cortex (S1), and it
      contained cytochrome oxidase dark regions, separated by light septa that formed
      isomorphs with some body parts. The rostral portion of this presumptive S1 cortex
      contained a face representation with a series of barrel-like cytochrome oxidase
      dark ovals that corresponded to the vibrissae on the snout. In caudolateral S1,
      light septa outline the palm and digits of the forepaw. Cortex caudal to S1, in
      the expected region of auditory cortex, responded to vibration, suggesting a
      modification of auditory cortex. Injections of wheat germ agglutinin-horseradish
      peroxidase into the cervical enlargement of the spinal cord revealed two dense
      foci of cortical cells that project to the spinal cord. The focus medial to the
      face region in S1 may correspond to primary motor cortex (M1). The second focus
      was coextensive with the somatosensory representation of the forelimb and the
      trunk in S1. The dense corticospinal projections from the forelimb representation
      of S1 and motor cortex may reflect sensorimotor specializations related to
      digging behaviors in moles.

PMID- 9034896
TI  - Evidence of spinocerebellar mossy fiber segregation in the juvenile staggerer
      cerebellum.
AB  - Developmental and experimental studies of climbing fiber and mossy fiber
      connectivity in the cerebellum have suggested that Purkinje cells are the
      critical organizing elements for connectivity patterns. This hypothesis is
      supported by evidence that spinocerebellar mossy fiber projections are abnormally
      diffuse in P25 sg/sg mutant mice in which the differentiation of a reduced number
      of sg/sg Purkinje cells is blocked due to a cell autonomous defect. However,
      mossy fiber distribution may be disrupted in sg/sg mutants not because of the
      Purkinje cell deficits, but because of the death of virtually all granule cells
      following the 4th postnatal week. To test this hypothesis, we have analyzed the
      distribution of wheat germ agglutinin-horseradish peroxidase (WGA-HRP)-labeled
      spinocerebellar mossy fiber terminals in sg/sg mutants at the end of the period
      of granule cell genesis (postnatal day [P] 12-P13) and before massive granule
      cell death (P16). Two percent WGA-HRP was injected into the lower thoracic/upper
      lumbar region of the spinal cord of eight homozygous sg/sg mutants (P12-P16) and
      five controls (+/sg and +/+). We have found that spinocerebellar mossy fibers
      segregate into distinct terminal fields in the anterior cerebellar lobules of P12
      to P16 sg/sg mutants, although the medial-lateral distribution of spinocerebellar
      mossy fiber projections is different from controls. The results from this study
      and previous analysis of sg/sg mutants support the hypothesis that topographic
      cues are expressed in the early postnatal staggerer mutant, but mossy fiber
      terminals become disorganized or retract as granule cells die in the older
      staggerer mutant. J. Comp. Neurol. 378:354-362, 1997.

PMID- 9034897
TI  - Distribution of calretinin-immunoreactivity in the rat entorhinal cortex:
      coexistence with GABA.
AB  - Inhibitory neurons in the entorhinal cortex control information flow between the
      cortical areas and the hippocampus. We characterized the inhibitory circuits in
      the rat entorhinal cortex by analyzing the distribution of calretinin
      immunoreactivity and its colocalization with glutamate decarboxylase (GAD) and
      gamma-aminobutyric acid (GABA). The location of calretinin-immunoreactive (IR)
      neurons and terminals varies between the different layers and subfields of the
      entorhinal cortex. The immunopositive neurons can be divided into two major
      morphological classes: bipolar and multipolar, which have two or more long,
      aspiny or sparsely spiny dendrites that extend through several layers. In
      addition, there are unclassified immunopositive neurons that have large lightly
      stained somata. They are located primarily in layer V. Colocalization analyses
      with GAD and GABA revealed that approximately 40% (657 out of 1,777) of all
      calretinin-IR cells within the entorhinal cortex contain GAD or GABA. In layers I
      III, over 90% of the calretinin-IR neurons contain GAD or GABA. In layers V-VI,
      however, most of the calretinin-IR neurons do not colocalize with either GAD or
      GABA. The distribution patterns of calretinin-immunoreactivity in the entorhinal
      cortex is consistent with the partitioning of the rat entorhinal cortex into six
      subfields. Furthermore, calretinin is expressed in a morphologically
      heterogeneous population of cells in the rat entorhinal cortex which includes
      both GABAergic and non-GABAergic neurons.

PMID- 9034898
TI  - Terminal morphology of two branches arising from a single stem-axon of pretectal
      (PSm) neurons in the common carp.
AB  - The induction of postsynaptic structures by presynaptic terminals is suggested in
      a teleost brain. Neurons in the nucleus pretectalis superficialis pars
      magnocellularis (PSm) in the common carp are known to send fibers to the corpus
      mamillare (CM) and the nucleus lateralis valvulae (NLV). Individual axons of PSm
      neurons bifurcate (or give off an axon collateral), both of which reach the
      target areas in the CM and NLV. The morphology of horseradish peroxidase-labeled
      terminals in the CM and NLV appears quite different in light microscopy.
      Terminals in the CM appear as a fine network of beaded (2-4 microns in diameter)
      fibers, while those in the NLV are larger (8-12 microns in transverse diameter)
      and cup-shaped, partially enveloping the soma of individual NLV neurons. In
      electron microscopy, however, these synapses in the CM and NLV share several
      ultrastructural similarities. Small (0.2 to 0.4-micron thick, 0.4 to 0.7-micron
      long) spine-like protrusions arising from dendrites in the CM, and from cell
      bodies in the NLV, invaginate into the axon terminals, and the synaptic junctions
      are always formed at the base of the protrusion in both areas. Development of
      this unusual morphology is inferred to be directed from the presynaptic side. The
      morphological similarity of the spine-like protrusions to the "spinule," which is
      thought to be formed in response to synaptic activation, is discussed.

PMID- 9034899
TI  - Light and dark cells of rat vallate taste buds are morphologically distinct cell
      types.
AB  - Cells of mammalian taste buds have been classified into morphological types based
      on ultrastructural criteria, but investigators have disagreed as to whether these
      are distinct cell types or the extremes of a continuum. To address this issue, we
      examined taste buds from rat vallate papillae that had been sectioned
      transversely, rather than longitudinally, to their longest axis. In these
      transverse sections, dark (Type I) and light (Type II) cells were easily
      distinguished by their relative electron density, shape and topological
      relationships. Cells with electron-lucent cytoplasm (light cells) were circular
      or oval in outline, while those with electron-dense cytoplasm (dark cells) had an
      irregular outline with sheetlike cytoplasmic projections that separated adjacent
      light cells. A hierarchical cluster analysis of 314 cells across five
      morphological parameters (cell shape and area, and nuclear ellipticity, electron
      density and invagination) revealed two distinct groups of cells, which largely
      corresponded to the dark and light cells identified visually. These cells were
      not continuously distributed within a principal components factor solution.
      Differences in the means for dark and light cells were highly significant for
      each morphological parameter, but within either cell type, changes in one
      parameter correlated little with changes in any other. These analyses all failed
      to reveal cells with a consistent set of intermediate characteristics, suggesting
      that dark and light cells of rat vallate taste buds are distinct cell types
      rather than extremes of a continuum. Sections of taste buds were stained with
      antibodies to several carbohydrates, then observed by indirect
      immunofluorescence. Optical sections taken with a confocal laser-scanning
      microscope showed that the Lewis antigen was present only on spindle-shaped cells
      with circular or oval outlines and lacking transverse projections; these
      characteristic shapes matched those of light cells seen by electron microscopy.
      The H blood group antigen and the 2B8 epitope appeared at most cell-cell
      interfaces in the bud and are present on dark cells and possibly on some light
      cells. These findings relate molecular markers to morphological phenotypes and
      should facilitate future studies of taste cell turnover, development and
      regeneration.

PMID- 9034900
TI  - Distribution, quantification, and morphological characteristics of serotonin
      immunoreactive cells of the supralemniscal nucleus (B9) and pontomesencephalic
      reticular formation in the rat.
AB  - In their initial report on the rat, Dahlstrom and Fuxe ([1964] Acta Physiol.
      Scand. 62:1-55) identified nine brainstem serotonin-containing cell groups, which
      they termed B1-B9. B9 has received considerably less attention than other
      serotonergic nuclei (B1-B8) due in part to the fact that its precise location and
      extent have not been well documented in subprimates. B9 (supralemniscal nucleus;
      SLN) has been viewed as a minor serotonergic cell group. In addition, 5
      hydroxytryptamine (5-HT)-containing cells have been shown to be only sparsely
      distributed throughout the pontomesencephalic reticular formation (PMRF). By
      using 5-HT immunohistochemical techniques, we examined the distribution and
      morphological characteristics of SLN and PMRF 5-HT neurons of the
      pontomesencephalic tegmentum. We showed that 5-HT cells of both SLN and the PMRF
      extend rostrocaudally from the rostral midbrain to the midpons. 5-HT SLN cells
      are located within or dorsal to the medial lemniscus (ML); those of the PMRF are
      widely distributed throughout the PMRF. The mean numbers of 5-HT containing cells
      in the SLN, PMRF, dorsal raphe, and median raphe nuclei were 4,571, 1,948,
      15,191, and 4,114, respectively. The SLN (B9) contains more 5-HT neurons than any
      serotonergic group other than the dorsal raphe nucleus. The dendrites of both SLN
      and PMRF 5-HT cells are primarily oriented mediolaterally and generally extend
      for long distances (75-300 microns), running perpendicular to the fibers of the
      ML (SLN) or, to those coursing through the brainstem (PMRF). The present
      anatomical delineation of SLN and PMRF shows that they are major 5-HT-containing
      cell groups in the rat and provides the foundation for the further examination of
      their properties and functions.

PMID- 9034901
TI  - Central projection of calcitonin gene-related peptide (CGRP)- and substance P
      (SP)-immunoreactive trigeminal primary neurons in the rat.
AB  - Substance P (SP) is implicated in transmission of primary afferent nociceptive
      signals. In primary neurons, SP is colocalized with calcitonin gene-related
      peptide (CGRP), which is another neuropeptide marker for small to medium primary
      neurons. CGRP coreleased with SP augments the postsynaptic effect of SP and
      thereby modulates the nociceptive transmission. This study demonstrates the
      distribution of CGRP-like immunoreactivity (-ir) and SP-ir in the lower brainstem
      of normal rats and after trigeminal rhizotomy or tractotomy at the level of
      subnucleus interpolaris (Vi). By comparing the results obtained from normal and
      deafferented rats, we analyzed the central projection of trigeminal primary
      nociceptors. The CGRP-immunoreactive (-ir) trigeminal primaries projected to the
      entire rostrocaudal extent of the spinal trigeminal nucleus, the principal
      nucleus (PrV), the paratrigeminal nucleus (paraV), and the lateral subnucleus of
      solitary tract nucleus (STN) on the ipsilateral side. The trigeminal primaries
      projecting to the spinal trigeminal nucleus, paraV and STN also contained SP-ir.
      The ipsilateral trigeminal primaries were the exclusive source of CGRP-ir
      terminals in the PrV, the Vi and the dorsomedial nucleus within the subnucleus
      oralis (Vo). The medullary dorsal horn (MDH) and the lateral edge of Vo received
      convergent CGRP-ir projection from the ipsilateral trigeminal primaries and other
      neurons. The glossopharyngeal and vagal primaries are candidates for the source
      of CGRP-ir projection to the Vo and the MDH, while the dorsal root axons supply
      the MDH with CGRP-ir terminals. In addition, contralateral primary neurons
      crossing the midline appear to contain CGRP and to terminate in the MDH.

PMID- 9034902
TI  - New structure, the "olfactory pit," in human olfactory mucosa.
AB  - A whole-mount immunocytochemical method was devised to study the olfactory
      receptor neurons on the surface of the human olfactory mucosal sheet. Antibodies
      to neuron-specific tubulin and/or microtubule-associated protein 5 and
      phosphorylated neurofilament protein were used. Specimens taken at autopsy from
      56 patients ranging in age from 2 days to 92 years revealed a structure not
      previously described, an olfactory pit. Round or oval openings with a diameter of
      50 to 500 microns were observed on the surface of the olfactory epithelium in the
      whole-mount specimen. The morphology, number, and distribution of these openings
      varied among the different individuals. A detailed analysis of these structures
      was carried out by rehydrating and sectioning the whole-mount specimens. The
      olfactory pit (OP) is a blind pouch lined with olfactory epithelium (OE), which
      appears as an invagination of OE into the connective tissue, with a depth varying
      between 150 and 200 microns. In some sections through an OP, a thick axon bundle
      emerging from the bottom of the pouch was visible. The extension and termination
      of this axon bundle in the central nervous system has not been explored. We have
      found OPs in monkey olfactory mucosa, but none in rodents. The function of the
      pit specialization is unclear, but it appears to be a feature of normal, young
      epithelium. The configuration of the blind pouch may prolong odorant association
      with the olfactory receptor neurons, or the OP may contain specialized neurons
      that have not yet been recognized by morphological, biochemical, or functional
      techniques.

PMID- 9034903
TI  - Vesicular acetylcholine transporter (VAChT) protein: a novel and unique marker
      for cholinergic neurons in the central and peripheral nervous systems.
AB  - Acetylcholine (ACh) is synthesized in nerve terminals from choline and acetyl
      coenzyme A by the cytoplasmic enzyme choline acetyltransferase (ChAT). The
      neurotransmitter is thereafter transported into synaptic vesicles, where it is
      stored until release. cDNA clones encoding a vesicular ACh transporter (VAChT)
      were recently isolated. In this paper, we report on the generation of highly
      specific goat polyclonal antisera to the rat VAChT protein by using a synthetic
      carboxy-terminal 20-amino-acid peptide sequence as an immunogen. Characterization
      of the antisera revealed recognition of VAChT, but not vesicular monoamine
      transporter (VMAT) protein, in transfected CV-1 cells. VAChT immunoreactivity was
      also detected in cells that endogenously express the protein, such as in PC12
      cells and in primary cultures of spinal motoneurons. Absorption controls showed
      that the VAChT antisera could be completely blocked at the 10(-5) M concentration
      by cognate peptide used for immunization. The antisera cross-reacted with the
      VAChT protein in rat and mouse but not in guinea pig, rabbit, or cat.
      Immunohistochemistry and confocal laser microscopy, using the goat VAChT
      antisera, showed strong immunoreactivity in discrete fibers and neuronal cell
      bodies of the central and peripheral nervous systems. Within cell bodies and
      axonal nerve terminals, as well as in dendrites, the staining appeared granular,
      presumably representing labeling of synaptic vesicles containing ACh. In the rat
      central nervous system, VAChT-positive cell bodies were demonstrated in the
      cerebral cortex, striatum, septum, nucleus basalis, medial habenula, mesopontine
      complex, cranial, and autonomic and spinal motor nuclei and in the
      intermediomedial region near the central canal. High densities of VAChT
      immunoreactive axonal fibers were encountered in areas such as the olfactory
      bulb, cerebral cortex, striatum, basal forebrain, amygdala, thalamus,
      hypothalamus including median eminence, hippocampal formation, superior
      colliculus, interpeduncular nucleus, and pedunculopontine and laterodorsal
      tegmental nuclei. In cranial and spinal motor nuclei, particularly large
      varicosities were seen in close proximity to the motoneuron cell somata and their
      proximal dendrites. In the peripheral nervous system, VAChT immunoreactivity was
      also detected in motor endplates of skeletal muscle as well as in fibers of
      sympathetic and parasympathetic abdominal ganglia, heart atrium, respiratory
      tract, gastrointestinal tract, pancreas, adrenal medulla, male genitourinary
      tract, and salivary and lacrimal glands. Direct double labeling revealed
      colocalization of VAChT and ChAT immunoreactivity in neurons. The results show
      that VAChT antisera represent novel and unique tools for the study of cholinergic
      neurons in the central and peripheral nervous systems.

PMID- 9034904
TI  - Anatomical localization and time course of Fos expression following soman-induced
      seizures.
AB  - Soman (pinacolymethylphosphonofluoridate), a highly potent, irreversible
      inhibitor of cholinesterase, causes intense convulsions, neuropathology and,
      ultimately, death. There is evidence that certain brain structures are
      selectively vulnerable to the pathological consequences of soman-induced
      seizures. A working hypothesis is that central nervous system (CNS) structures
      with the earliest and most severe signs of neuropathology may be key sites for
      the initiation of the seizures. Fos, the immediate-early gene product, increases
      rapidly in several animal seizure models. Thus, we reasoned that the earliest
      brain regions to express Fos might be involved in the initiation and maintenance
      of soman-induced convulsions. To assess this, rats were injected with a single,
      convulsive dose of soman (77.7 micrograms/kg, i.m.). The animals were euthanized
      and processed for immunocytochemical analysis at several time points. Robust Fos
      expression was seen in layer II of the piriform cortex and the noradrenergic
      nucleus locus coeruleus within 30-45 minutes. One hour following soman injection,
      staining was more intense in the piriform cortex layer II and in the locus
      coeruleus. In addition, Fos was evident in the piriform cortex layer III, the
      entorhinal cortex, the endopiriform nucleus, the olfactory tubercle, the anterior
      olfactory nucleus and the main olfactory bulb. By 2 hours, Fos staining was
      present throughout the cerebral cortex, thalamus, caudate-putamen and the
      hippocampus. At 8 hours and beyond, Fos expression returned to control levels
      throughout the CNS except for the piriform cortex and the locus coeruleus which
      still had robust labeling. By 24 hours, neuropathology was evident throughout the
      rostral-caudal extent of layer II of the piriform cortex. The rapid induction of
      Fos in the piriform cortex and the locus coeruleus, taken together with previous
      anatomical, eletrophysiological and neurochemical studies, suggests that
      prolonged, excessive exposure to synaptically released acetylcholine and
      norepinephrine triggers the production of soman-induced seizures initially in the
      piriform cortex and subsequently in other cortical and subcortical structures.

PMID- 9034905
TI  - Soman-induced seizures rapidly activate astrocytes and microglia in discrete
      brain regions.
AB  - Neurons in the piriform cortex and the pontine nucleus locus coeruleus express
      elevated levels of the immediate early gene protein product, Fos, within 30-45
      minutes of a seizurogenic dose of the anticholinesterase, soman (Zimmer et al.,
      [1997] J. Comp. Neurol. 378:468-481). By 24 hours following soman injection,
      there is marked neuropathology in the piriform cortex. These findings suggest
      selective, regional vulnerability in response to the seizurogenic actions of
      soman. In the present study, we determined that soman-induced seizures also cause
      selective, rapid activation of astrocytes and microglia in the piriform cortex
      and other brain regions. Animals were killed at different intervals between 1
      hour and 24 hours after a convulsive dose of soman. Brain sections were processed
      for immunocytochemical detection of astrocytes with antibodies against glial
      fibrillary acidic protein, and microglia and macrophages with antibodies against
      the complement receptor 3 protein, OX-42. The results demonstrate that following
      soman administration: (1) there is a rapid increase in glial fibrillary acidic
      protein staining in astrocytes of the piriform cortex (1 hour); (ii) reactive
      astrocytes are specifically restricted to layer II and the superficial boundaries
      of layer III of the piriform cortex. These are the same layers in which neurons
      express Fos within 30-45 minutes following soman administration; (3) between 1
      and 4 hours, resting (ramified) microglia in the piriform cortex and the
      hippocampus alter their morphology to resemble active microglia. From 4-8 hours,
      active microglia undergo morphological changes characteristic of reactive
      microglia that resemble macrophages. Taken together, these observations indicate
      that astrocytes and microglia in brain regions susceptible to soman become
      rapidly "reactive" in response to seizures. The highly specific anatomical
      codistribution of reactive glia and Fos-expressing neurons suggests that
      intensely active neurons provide local signals that trigger reactive changes in
      neighboring glia.

PMID- 9034906
TI  - Alpha 2A-adrenergic receptors are expressed by diverse cell types in the fetal
      primate cerebral wall.
AB  - The cellular elements of the fetal monkey cerebral wall expressing alpha 2A, the
      most common subtype of the alpha 2 receptor class, were examined by using
      nonisotopic in situ hybridization and immunohistochemistry with double-labeling
      for cell type-specific markers. At the three embryonic ages examined, E70, E90,
      and E120, alpha 2A receptors were expressed throughout the embryonic cerebral
      wall. In the E70 and E90 fetuses, alpha 2A receptors were observed in most cells
      of the proliferative zones. Some alpha 2A-positive cells also expressed a
      proliferation-associated antigen, Ki-67, suggesting that the receptors are
      present in dividing cells. Furthermore, at E90, alpha 2A receptors were detected
      on fibers passing between the ventricular and subventricular proliferative zones.
      At all ages studied, alpha 2A receptors were expressed by migrating neurons in
      the intermediate zone, characterized by a spindle-like shape, radial alignment,
      and close association with radial glia. alpha 2A receptors were also expressed by
      postmigrational microtubule-associated protein-2-positive neurons of the
      intermediate and subplate zones and the cortical plate. In the marginal zone,
      alpha 2A receptors were present in the Cajal-Retzius neurons. Finally, alpha 2A
      receptors were seen in the glial fibrillary acidic protein-positive cells at all
      ages studied. In addition, dopamine-beta-hydroxylase immunohistochemistry,
      employed to determine the potential source of noradrenaline in the embryonic
      cerebral wall, revealed noradrenergic innervation in the marginal, subplate, and
      intermediate zones of the monkey occipital lobe as early as E70. Based on our
      observations and available data on alpha 2A signal transduction pathways, we
      propose that these receptors are involved in regulating the generation,
      migration, and maturation of cerebral cortical cells.

PMID- 9034907
TI  - Distribution of trigeminohypothalamic and spinohypothalamic tract neurons
      displaying substance P receptor-like immunoreactivity in the rat.
AB  - Primary afferent neurons containing substance P (SP) are apparently implicated in
      the transmission of noxious information from the periphery to the central nervous
      system, and SP released from primary afferent neurons acts on second-order
      neurons with the SP receptor (SPR). In the rat, nociceptive information reached
      the hypothalamus not only through indirect pathways but also directly through
      trigeminohypothalamic and spinohypothalamic pathways. Thus, in the present study,
      the distribution pattern of trigeminohypothalamic and spinohypothalamic tract
      neurons showing SPR-like immunoreactivity (SPR-LI) was examined in the rat by a
      retrograde tract-tracing method combined with immunofluorescence histochemistry
      for SPR. A substantial number of trigeminal and spinal neurons with SPR-LI were
      retrogradely labeled with Fluoro-Gold (FG) injected into the hypothalamic
      regions. These neurons were distributed mainly in lamina I of the medullary and
      spinal dorsal horns, lateral spinal nucleus, regions around the central canal of
      the spinal cord, and the lateral aspect of the deep part of the spinal dorsal
      horn. A number of SPR-LI neurons in the spinal parasympathetic nucleus were
      labeled with FG injected into the area around the paraventricular hypothalamic
      nucleus. Some SPR-LI neurons in the lateral spinal nucleus and the lateral aspect
      of the deep part of the spinal dorsal horn were also labeled with FG injected
      into the septal region. On the basis of the distribution areas of SPR-LI
      trigeminal and spinal neurons projecting to the hypothalamic and septal regions,
      it is likely that these neurons are involved in the transmission of somatic
      and/or visceral noxious information.

PMID- 9034908
TI  - Subcellular localization of nitric oxide synthase in the cerebral ventricular
      system, subfornical organ, area postrema, and blood vessels of the rat brain.
AB  - The distribution of neuronal nitric oxide synthase (nNOS) has been studied in the
      more rostral portion of the lateral ventricle, subfornical organ, area postrema
      and blood vessels of the rat central nervous system. nNOS was located by means of
      a specific polyclonal antibody, by using light and electron microscopy. Light
      microscopy showed immunoreactive varicose nerve fibers and terminal boutons-like
      structures in the lateral ventricle, positioned in supra- and subependimal areas.
      The spatial relationships between immunoreactive neuronal processes and the wall
      of the intracerebral blood vessels were studied. Electron microscopy showed
      numerous nerve fibers in the wall of the lateral ventricle; many were nNos
      immunoreactive and established very close contact with ependymal cells.
      Immunoreactive neurons and processes were found in the subependymal plate of the
      ventricular wall, the subfornical organ, the area postrema, and the circularis
      nucleus of the hypothalamus. In these last three areas, the immunoreactive
      neurons were found close to the perivascular space of fenestrated and
      nonfenestrated blood vessels. The nNOS immunoreactivity was localized to the
      endoplasmic reticulum, cisterns, ribosomes, neurotubules, and in the inner part
      of the external membrane. In the terminal boutons, the reaction product was found
      surrounding the vesicle membranes. This distribution showed nNOS as a
      predominantly membrane-bound protein. The nitrergic nerve fibers present in the
      wall of the ventricular system might regulate metabolic functions as well as
      neurotransmission in the subfornical organ, area postrema and circularis nucleus
      of the hypothalamus.

PMID- 9034909
TI  - Species differences in vasopressin receptor binding are evident early in
      development: comparative anatomic studies in prairie and montane voles.
AB  - Monogamous prairie voles (Microtus ochrogaster) and promiscuous montane voles
      (Microtus montanus) exhibit remarkable differences in the distribution of
      vasopressin (AVP) receptors in the adult brain. This difference in receptor
      distribution is associated with species differences in the behaviors, including
      pair bond formation and paternal care, found selectively in the monogamous vole.
      To investigate a potential mechanism for this species difference in AVP
      receptors, the present study examined the ontogeny of receptor binding in the two
      species to determine whether the adult maps arose from a shared pattern in
      development. By using 125I-linear-AVP, which is a selective high-affinity ligand
      for the V1a receptor, we found early appearance and transient expression of AVP
      receptor binding during postnatal development in both species. However, the
      ontogenetic patterns of regional AVP receptor binding were species specific. In
      the diagonal band, the bed nucleus of the stria terminalis, and the central
      nucleus of the amygdala, prairie voles had higher AVP receptor binding at birth
      than montane voles, and this difference persisted with little variation into
      adulthood. In these areas, therefore, species differences in AVP receptor binding
      appeared to be determined primarily by genetic or prenatal factors. In the
      lateral septum, both species had low levels of AVP receptor binding at birth.
      Thereafter, the binding increased rapidly in montane voles, but it remained
      unchanged in prairie voles. In the cingulate cortex, AVP receptor binding in
      prairie voles showed a peak in early development with a subsequent decline and
      reached the adult level at weaning, whereas the binding in montane voles remained
      unchanged into adulthood. A similar but opposite pattern was found in the
      frontoparietal cortex, in which AVP receptor binding showed an early peak in
      montane voles but did not change significantly in prairie voles. These results
      demonstrate that 1) species differences in regional AVP receptor binding are
      evident in the early postnatal period and, in several areas, may be determined by
      genetic or prenatal factors, and 2) AVP may target brain areas differently in
      infant and adult prairie and montane voles and, thus, could exert differential
      effects on the organization of the central nervous system in the two species of
      voles.

PMID- 9034910
TI  - Distribution of the ten known laminin chains in the pathways and targets of
      developing sensory axons.
AB  - Laminins are heterotrimers of alpha, beta, and gamma chains. At present, five
      alpha, three beta, and two gamma chains have been described. The best
      characterized laminin (laminin 1 = alpha 1, beta 1, gamma 1) promotes neurite
      outgrowth from virtually all classes of developing neurons, implying that
      laminins may serve as axon guidance molecules in vivo. Moreover, different
      laminin trimers exert distinct effects on subsets of laminin-1-responsive cells,
      suggesting that isoform diversity may underlie some axonal choices in vivo. As a
      first step toward evaluating these hypotheses, we have documented the expression
      patterns of all 10-known laminin chains in the peripheral nervous system and
      spinal cord of the murine embryo. The alpha 2, alpha 4, beta 1, and gamma 1
      chains are expressed in peripheral axonal pathways by embryonic day (E) 11.5,
      when sensory and motor axonal outgrowth is underway. Thus, laminins (but not
      laminin 1) may promote peripheral axonal outgrowth. By E 13.5, laminin chains are
      differentially expressed in the limb-bud, with prominent expression of alpha 2
      and alpha 4 in muscle and of alpha 3 and alpha 5 in skin. This pattern raises the
      possibility that laminin isoform diversity contributes to the ability of
      cutaneous and muscle sensory axons to distinguish their targets. Later in
      development, some chains (e.g., alpha 2, alpha 4, and beta 1) are downregulated
      in peripheral nerve while others (e.g., gamma 1), continue to be expressed by
      Schwann cells into adulthood. In contrast to peripheral nerves and ganglia,
      laminin chains are expressed at low levels, if at all, in the developing spinal
      cord gray matter.

PMID- 9034911
TI  - Corticothalamic connections of extrastriate visual areas in rhesus monkeys.
AB  - Corticothalamic connections of extrastriate visual areas were studied by using
      the autoradiographic anterograde tracing technique. The results show that the
      medial extrastriate region above the calcarine sulcus projects mainly to the
      lateral pulvinar (PL), medial pulvinar (PM), and lateral posterior (LP) nuclei.
      In addition, the dorsal portion of the medial region has connections to the
      lateral dorsal (LD) as well as to intralaminar nuclei. The dorsolateral
      extrastriate region projects strongly to the PL and LP nuclei, to the PM and
      inferior pulvinar (PI) nuclei, and to the LD and intralaminar nuclei. The lateral
      extrastriate region above the inferior occipital sulcus (IOS) has strong
      connections to both the PL and PI nuclei and has minor projections to the PM and
      oral pulvinar nuclei. The ventrolateral extrastriate region below the IOS
      projects mainly to the PI nucleus and to the caudal portion of the PL nucleus and
      has some projections to the PM nucleus. The ventromedial extrastriate region
      medial to the occipitotemporal sulcus has strong connections with the ventral and
      medial sectors of the PI nucleus. This region also projects to the caudal portion
      of the PL nucleus and has minor connections to the LP nucleus. Finally, the
      annectant gyrus projects to the PL nucleus and to the rostral portion of the PI
      nucleus and has minor connections to the PM nucleus. Thus, the medial and
      dorsolateral extrastriate regions are related mainly to the PL and LP nuclei as
      well as to intralaminar nuclei. In contrast, the ventrolateral and ventromedial
      regions are connected strongly with the PI nucleus. This connectional
      organization appears to reflect functional differentiation at the cortical level.

PMID- 9034912
TI  - Endoluminal treatment of arterial diseases using a stent-graft combination:
      reflections 20 years after the initial concept.

PMID- 9034913
TI  - Will contrast aortography become obsolete in the preoperative evaluation of
      abdominal aortic aneurysm for endovascular exclusion?

PMID- 9034914
TI  - European experience with a system for bifurcated stent-graft insertion.
AB  - PURPOSE: To test an endovascular aneurysm exclusion system in the presence of a
      wide range of challenging anatomic features. METHODS: Bifurcated endovascular
      stent-grafts were inserted in 52 patients and followed with serial computed
      tomography for up to 3 years. The device underwent several modifications during
      this time, the most significant of which represent the difference between the
      homemade (n = 42) and industry-made (n = 10) versions. RESULTS: The initial
      procedural success rate was 92% in the homemade group and 100% in the industry
      made group. In the 3 years of follow-up, the long-term success rate was 64% in
      the homemade group and 90% in the industry-made group. The primary reasons for
      failure in the homemade group were graft thrombosis due to kinking early in the
      series and proximal stent migration later in our experience. All cases of
      migration occurred when the neck was < 15 mm in length, the neck was lined with
      thrombus, or the stent was implanted > 15 mm from the renal arteries. Kinking was
      subsequently overcome by implanting Wallstents throughout the graft limbs. The
      sole failure in the industry-made group was a case in which collateral perfusion
      reached the aneurysm through patent lumbar arteries. CONCLUSIONS: The fruits of
      this experience are a better technique, a better device, and, most importantly, a
      better understanding of the system's limits, as reflected in the current
      selection criteria.

PMID- 9034915
TI  - Changing aneurysmal morphology after endovascular grafting: relation to leakage
      or persistent perfusion.
AB  - PURPOSE: To relate changing abdominal aortic aneurysm (AAA) morphology after
      endovascular grafting to the presence of leakage, collateral perfusion, and other
      factors. METHODS: Thirty-five patients who underwent successful AAA endovascular
      grafting were evaluated. Self-expanding Z-stents and Dacron grafts were applied
      in bifurcated and aortomonoiliac systems. Postoperative diameter changes were
      calculated from repeated spiral computed tomographic scans, angiograms, and
      ultrasonic phase-locked echo-tracking scans during a median 6-month follow-up
      (interquartile range [IQR] 3 to 12). RESULTS: At 12 months, the diameters of
      completely excluded aneurysms had decreased 6 mm (IQR 2 to 11; p = 0.006). The
      proximal graft-anchoring stents had dilated 2 mm (IQR 0.5 to 3.3; p = 0.01). The
      aortic diameters immediately below the renal arteries but above the stents had
      not changed. Endoleakage and collateral perfusion (n = 13) were each associated
      with preserved aneurysm size and a 12 times higher risk of aneurysm dilation.
      After the leakage or the collateral perfusion had been treated, the aneurysm size
      decreased. Aneurysms with extensive intraluminal thrombi presented a reduced risk
      of leakage or perfusion. CONCLUSIONS: The diameters of endovascularly excluded
      AAAs decrease, except in cases of leakage or perfusion. Careful follow-up of
      patients with aortic endografts is necessary.

PMID- 9034916
TI  - The ins and outs of the excluded abdominal aortic aneurysm: decreasing diameters
      and dilating necks.

PMID- 9034917
TI  - Ultrasound-based quantification of emboli during conventional and endovascular
      aneurysm repair.
AB  - PURPOSE: To differentiate and quantify the type and number of lower limb emboli
      occurring during endovascular aneurysm repair, as compared to conventional
      surgery. METHODS: Thirty-eight patients underwent elective infrarenal aneurysm
      repair using a conventional surgical approach in 18 and an endovascular procedure
      in 20. Emboli were detected using a Doppler ultrasound system with a 2-MHz
      transducer interrogating the mid superficial femoral artery. Lower limb emboli
      were differentiated as particulate or gaseous based on the physical distance
      traversed by the embolic signal. RESULTS: Significantly more particulate (median
      108 versus 59, p = 0.015) and gaseous (134 versus 46, p = 0.008) emboli were
      detected during endovascular aneurysm repair as compared to conventional surgery.
      Clinically, no case of massive microembolization occurred in either group, but
      one patient in the conventional group required a femoral embolectomy, and three
      patients undergoing endovascular repair developed self-limiting trash feet
      postoperatively. In patients undergoing endovascular aortomonoiliac aneurysm
      repair, there was only a poor correlation between the number of particulate
      emboli and either procedural duration or operator experience. CONCLUSIONS: The
      apparent lack of a relationship between particulate embolization and operative
      time or technical experience suggests that manipulation of endoluminal devices
      within the aneurysm sac may not be the sole determinant of intraprocedural
      embolization. Other as yet undetermined factors may predict patients at high risk
      for massive embolization.

PMID- 9034918
TI  - Morphometry and classification in abdominal aortic aneurysms: patient selection
      for endovascular and open surgery.
AB  - PURPOSE: To evaluate the anatomic morphology of abdominal aortic aneurysms (AAAs)
      and compose a classification system to facilitate patient selection for
      endovascular graft (EVG) repair. METHODS: Data on 242 consecutive AAA patients
      evaluated on a nonemergent basis in a 3.5-year period to July 1996 were
      prospectively entered into a registry. Patients were examined using sequential
      intravenous spiral computed tomographic angiography and intraarterial digital
      subtraction angiography. The data collected and analyzed included: diameters of
      the supra- and infrarenal aorta, aneurysm, aortoiliac bifurcation, and iliac
      arteries; lengths of the proximal neck, distal cuff, and aneurysm; degrees of
      iliac artery tortuosity; and occlusion of the visceral, renal, or iliac arteries.
      RESULTS: The 242 aneurysms could be easily grouped into three distinctive
      categories related to the extent of the aneurysmal disease. Type I AAAs (11.2%)
      had nondilated, thrombus-free infrarenal (15 mm) necks and distal (10 mm) cuffs
      appropriate for EVG anchoring. In type II and its subgroups (72.3%), a sufficient
      proximal neck was present, but the aneurysm extended into the iliac arteries; 56%
      of these were eligible for a bifurcated endograft. In type III (16.5%), a
      sufficient proximal neck was missing, independent of distal involvement. In all,
      51.7% were good EVG candidates based on AAA morphology. Taking into consideration
      relevant concomitant vascular diseases, proximal iliac kinking, and iliac, renal,
      or visceral occlusive disease, only 30.2% of the population were potential
      candidates for an efficient and secure EVG repair using the devices currently
      available. CONCLUSIONS: In contrast to classical open repair, detailed
      preoperative measurements are recommended for EVG planning. The use of liberal
      EVG indications may lead to a higher incidence of complications, whereas
      restrictive morphology-based selection criteria may offer excellent results.

PMID- 9034919
TI  - Intravascular ultrasound: the ultimate tool for abdominal aortic aneurysm
      assessment and endovascular graft delivery.
AB  - Intravascular ultrasound (IVUS) imaging is a relatively new, rapidly evolving
      technology that enables precise catheter-based assessment of the dimensions and
      morphology of vascular structures and lesions. In extensive preclinical
      laboratory developmental studies and in clinical cases of endograft deployment
      for treatment of abdominal aortic aneurysms, we have found IVUS invaluable for
      determining key parameters of aortic morphology before and during interventions
      and for assessing the accuracy of deployment after device placement. By combining
      the IVUS data with information obtained from angiography, magnetic resonance
      imaging, and computed tomography (axial and three-dimensional reconstructions),
      we have been able to size devices and choose optimal fixation sites to prevent
      endoleaks and maintain luminal patency acutely and in the long term.

PMID- 9034920
TI  - Regional anesthesia for endovascular treatment of abdominal aortic aneurysms.
AB  - PURPOSE: To investigate the feasibility of regional anesthesia for endovascular
      repair of abdominal aortic aneurysms (AAAs). METHODS: Since February 1995, 21
      patients (17 men and 4 women; median age 67 years, range 49 to 80) have been
      treated with endovascular technique for true infrarenal AAA using Mialhe Stentor
      bifurcated grafts. A single dose of spinal anesthesia combined with epidural
      anesthesia was used in all procedures. Electrocardiography and arterial blood
      pressure were monitored. RESULTS: No cases of emboli, hematoma, or graft
      migration were seen, and there were no reoperations or conversions to operation.
      Arterial blood pressure was stable at a satisfactory level from induction of
      anesthesia throughout the procedure, and there was no period of clinically
      significant hypotension during any implantation. One patient died on the second
      postoperative day from cardiac and renal insufficiency. Three endoleaks were
      observed during the procedure; one healed spontaneously within 5 weeks, and the
      other two were repaired by endovascular techniques after 1 and 4 months,
      respectively. During follow-up, one patient died at 6 months from pancreatic
      carcinoma. CONCLUSIONS: The application of regional anesthesia is feasible for
      endovascular treatment of AAA. The arterial blood pressure remained stable
      throughout the procedure, and all patients, with two exceptions, were mobilized
      on the first day and placed on a regular diet. Based on these early results, it
      appears that regional anesthesia is feasible, effective, and safe for
      endovascular AAA repair.

PMID- 9034921
TI  - Improved respiratory function and analgesia control after endovascular AAA
      repair.
AB  - PURPOSE: Endovascular abdominal aortic aneurysm (AAA) repair has been proposed as
      a minimally invasive alternative to conventional surgery and may offer
      significant advantages in respiratory function and analgesic requirements due to
      the absence of an abdominal incision. METHODS: Respiratory function and analgesic
      requirements were quantified in 22 age-matched patients undergoing aneurysm
      repair under general anesthesia. Twelve patients underwent endovascular aneurysm
      repair, while 10 AAA patients had conventional surgery. One endovascular patient
      required conversion to conventional repair. RESULTS: The endovascular group
      required postoperative artificial ventilation for a shorter time (6 versus 21
      hours, p < 0.05) and had lower PCA (patient-controlled analgesia) morphine
      consumption (41 versus 133 mg, p < 0.05) than the conventional group. The
      endovascular group also had significantly better forced expiratory volume and
      forced vital capacity at both 3 and 5 days when expressed as percentages of the
      preoperative values (p < 0.05). CONCLUSIONS: Endovascular AAA repair attenuates
      respiratory dysfunction associated with conventional surgery and reduces
      perioperative analgesia requirements.

PMID- 9034922
TI  - Ethical and legal issues related to endovascular graft investigation and early
      usage.

PMID- 9034923
TI  - The need for clinical trials of endovascular abdominal aortic aneurysm stent
      graft repair: The EUROSTAR Project. EUROpean collaborators on Stent-graft
      Techniques for abdominal aortic Aneurysm Repair.
AB  - EUROSTAR (EUROpean collaborators on Stent-graft Techniques for abdominal aortic
      Aneurysm Repair) was established for the purpose of combining and studying data
      on endovascular abdominal aortic aneurysm (AAA) repair, EUROSTAR is independent
      of any commercial interest and has as its ultimate goal an independent,
      scientifically reliable assessment of endovascular AAA grafting. A standardized
      case record form is used for data collection and transmission, and the database
      is maintained in a central registry office. A comprehensive set of clinical,
      imaging, technical, and laboratory data obtained at initial admission and follow
      up are recorded; these data are analyzed periodically and reports generated on
      the collated experience. As a first priority, an observational study without
      controls was initiated in July 1996 to address the issues of procedural safety,
      device durability, and long-term effect upon the aneurysms. Several ancillary
      studies have been initiated, including a "Retrieval and Analysis Study" for the
      evaluation of explanted devices. While a randomized study does not seem feasible
      at present, this may be organized at the appropriate time when the devices and
      techniques become more standardized.

PMID- 9034924
TI  - Successful endoluminal repair of arterial aneurysms by Wallstent prosthesis and
      PTFE graft: preliminary results with a new technique.
AB  - PURPOSE: To describe a new method of endovascular aneurysm exclusion using a
      Wallstent-PTFE vascular prosthesis in patients at high risk for surgery. METHODS
      AND RESULTS: Two patients with significant comoribidities refused surgery in
      favor of endoluminal grafting for treatment of aneurysms in the abdominal aorta
      and popliteal artery, respectively. Both endovascular procedures were performed
      percutaneously with local anesthesia using a low-profile customized endograft
      constructed of thin-walled, predilated polytetrafluoroethylene (PTFE) graft
      mounted on a Wallstent. In both cases, the aneurysm was excluded from the
      arterial circulation; there were no postprocedural complications. Follow-up
      evaluation with appropriate imaging at 8 months (popliteal aneurysm) and 2 months
      (abdominal aneurysm) revealed no endoleaks. CONCLUSIONS: Our preliminary results
      indicate that the Wallstent-PTFE graft, with its smaller diameter and flexible
      design, offers significant advantages over currently available devices for repair
      of arterial aneurysms. This method obviates the need for general anesthesia or
      surgical exposure for arterial repair, which would increase the risk of the
      procedure in these patients.

PMID- 9034925
TI  - Endoluminal graft exclusion of a proximal para-anastomotic pseudoaneurysm
      following aortobifemoral bypass.
AB  - PURPOSE: To describe a case of endoluminal graft exclusion of a proximal para
      anastomotic pseudoaneurysm that occurred 17 years following aortobifemoral bypass
      for occlusive disease. METHODS AND RESULTS: The lesion was found on abdominal
      ultrasound examination as part of a work-up for acute abdominal pain and upper
      gastrointestinal bleeding in a 67-year-old male. A 5-cm saccular pseudoaneurysm
      was confirmed by preintervention aortography and spiral computed tomography (CT)
      scanning. Because of the patient's acute symptoms and high-risk medical condition
      (cardiomyopathy), he was deemed a candidate for endoluminal bypass. At the time
      of intervention, intravascular ultrasound (IVUS) interrogation identified a 3.5
      cm-long separation of the existing aortic graft from the proximal aortic stump
      with a large pseudoaneurysm. The lesion was isolated and repaired by placement of
      an aortic-to-right iliac endoluminal bypass, ligation of the left limb of the
      aortofemoral graft, and femorofemoral bypass to restore blood flow to the lower
      extremities. Spiral CT scans at 48 hours and 3 months following the procedure
      confirmed complete isolation of the lesion. CONCLUSIONS: This case illustrates
      the feasibility of endografting for repair of aortic para-anastomotic
      pseudoaneurysms, and it also highlights the potential role of IVUS imaging in
      endoluminal graft deployment.

PMID- 9034926
TI  - A primer on common technical problems in endovascular surgery: know them to avoid
      them.

PMID- 9034927
TI  - Sclerotherapy resistant oesophageal varices: what are their clinical significance
      in prophylactic sclerotherapy?

PMID- 9034928
TI  - Distinctive portal venographic pattern in patients with sclerotherapy resistant
      oesophageal varices.
AB  - We performed prophylactic sclerotherapy in 350 patients with 'high risk'
      oesophageal varices (F2 or F3 with a moderate or severe red colour sign). Of
      these patients, eight exhibited sclerotherapy resistance (i.e. no significant
      reduction in the size of varices after five sessions of sclerotherapy). Thus, the
      prevalence of sclerotherapy resistant varices was 2%. Of 350 patients, 97
      underwent haemodynamic investigation before sclerotherapy. This group consisted
      of seven patients with sclerotherapy resistant varices and 90 patients with non
      resistant varices. Portal pressure, assessed by portal venous pressure gradient,
      was similar in these two groups (21.5 +/- 4.8 vs 19.8 +/- 5.0 mmHg, respectively;
      NS). However, the prevalence of the 'pipe-line' form of variceal feeding pattern
      (a large dilated left gastric vein running up the oesophagus) was higher in
      patients with resistant varices than in those with non-resistant varices (100 vs
      3%, respectively; P < 0.01) and the diameter of the left gastric vein was larger
      in patients with resistant varices than in those with non-resistant varices (12.4
      +/- 2.0 vs 7.8 +/- 2.3 mm, respectively; P < 0.01). Moreover, the extravariceal
      portosystemic shunt was poorly developed in patients with resistant varices
      compared with non-resistant varices (0 vs 52%, respectively; P < 0.05). We
      conclude that the pipe-line pattern, fed by a large left gastric vein and
      associated with poorly developed extravariceal portosystemic shunt, is a
      distinctive portal venographic feature of sclerotherapy resistant varices.

PMID- 9034929
TI  - Circadian occurrence of variceal bleeding in patients with liver cirrhosis.
AB  - Several clinical events have a rhythmicity over the 24 h period. We assessed the
      presence of periodic rhythm in the occurrence of haematemesis in patients with
      liver cirrhosis under different daylight regimens, namely during standard time
      and during daylight savings. Over a 48 month period there were 212 consecutive
      admissions of 118 cirrhotics with variceal bleeding. Complete data were available
      for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60
      (33.1%) started with melaena. One hundred and two (56%) episodes occurred during
      daylight savings and 79 (44%) occurred during standard time. The cosinor test
      showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45
      h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple
      component rhythmometry. The time peaks of onset of variceal haemorrhage did not
      change significantly during standard time and daylight savings. Patients with
      more than one haematemesis episode significantly bled over the same time
      interval. The present study confirms that over the 24 h period variceal bleeding
      in cirrhotic patients occurs with a predictable rhythmicity that does not seem to
      be under the control of the light-dark cycle. The finding of a chronorisk for
      variceal haemorrhage addresses specific questions for pathophysiological studies
      as well as for new treatment strategies.

PMID- 9034930
TI  - New approaches to the Budd-Chiari syndrome.
AB  - Recent research has led to an improved understanding of the aetiology of Budd
      Chiari syndrome in some patients. Fresh approaches and technical developments
      within methods of radiological intervention have added more effective options to
      its treatment. In this editorial we aim to summarize our understanding of the
      role of new aetiologies and new therapeutic approaches in the Budd-Chiari
      syndrome.

PMID- 9034931
TI  - Iron overload and liver fibrosis.
AB  - The pathogenesis of liver fibrosis in genetic haemochromatosis and other iron
      overload states remains enigmatic. Recent advances in the cellular and molecular
      pathogenesis of liver fibrosis have determined a central role for hepatic
      stellate cells. These become activated to a myofibroblastic phenotype following
      most forms of liver injury and are the major cellular source of collagens and
      other matrix proteins laid down in fibrotic liver. Similar changes have now been
      reported in the liver in genetic haemochromatosis, with activation of stellate
      cells becoming more prominent with increasing hepatic iron concentration. In
      contrast to other liver diseases, this apparently occurs in the absence of
      significant necroinflammatory change. Unravelling the mechanism of liver
      fibrogenesis in iron overload states may, therefore, provide important general
      insights into the pathogenesis of liver fibrosis. The present article reviews
      current knowledge of this field with emphasis on the role of lipid peroxidation,
      sideronecrosis of hepatocytes and spillover of iron to Kupffer cells. An attempt
      is made to draw these observations together with previous studies of the
      mechanisms of stellate cell activation in other models and diseases. A unifying
      hypothesis emerges that helps to define some of the next research questions in
      the pathogenic mechanisms of liver fibrosis in iron overload.

PMID- 9034932
TI  - UDP-glucuronosyltransferase in the regenerating rat liver.
AB  - In both acute and chronic liver disease in man, elimination of drugs metabolized
      by the cytochrome P450 (CYP) enzymes is impaired. In contrast, those drugs
      metabolized by UDP-glucuronosyltransferase (UGT) have a relatively normal
      elimination. Studies in rats with experimentally induced liver injury also show
      this relative preservation of glucuronidation. In liver disease, a number of
      factors, including inflammation, fibrosis and regeneration, may be associated
      with this differential effect on drug metabolism. Partial hepatectomy provides a
      model in which to isolate the effects of liver regeneration on drug metabolism.
      Partial hepatectomy or sham operation was performed in 24 male Sprague-Dawley
      rats and three rats from each group were studied at days 1, 2, 4 and 6.
      Comparison between CYP and UGT was made at the protein level using
      immunohistochemistry and immunoblotting probed with a polyclonal antibody to UGT,
      identifying both family 1 and family 2 isoforms, and an antibody to the CYP
      isoform CYP2C11. Steady state messenger RNA levels of four isoforms of UGT were
      assessed by northern blot analysis. By both immunohistochemistry and
      immunoblotting, the level of CYP protein decreased from day 2 to 6 after
      hepatectomy. In contrast, the UGT protein level was not altered by partial
      hepatectomy. Northern blot analysis of UGT isoforms demonstrated differential
      regulation of isoforms from the two major families. The UGT family 1 isoforms
      were initially markedly depressed following partial hepatectomy and then steadily
      rose over 6 days to greater than the level in controls. In contrast, there was an
      apparent increase in UGT2B1 mRNA (not significant) on day 2, while UGT2B3 mRNA
      was maintained over the six days. These results demonstrate that during hepatic
      regeneration the protein content of total UGT is normal, while CYP2C11 protein is
      markedly reduced. Northern blot analysis suggests that individual isoforms of UGT
      are differentially regulated during the regeneration process.

PMID- 9034933
TI  - Synthesis of secretory protein in regenerating liver of rat after partial
      hepatectomy.
AB  - Albumin immunoreactivity in the liver was examined on days 2, 5 and 10 after two
      thirds partial hepatectomy by light and ultrastructural immunoperoxidase methods
      and the ultrastructural area of the rough endoplasmic reticulum (ER) in
      hepatocytes was measured. Albumin immunoreactivity was seen in the rough ER and
      Golgi apparatus of all hepatocytes in the hepatectomized liver and
      ultrastructural analysis showed a significantly greater area of rough ER on day 5
      than on days 2 or 10. Albumin mRNA was studied by the in situ hybridization
      technique using radioisotopes and their numbers were determined visually. Albumin
      mRNA was present as grains in all hepatocytes and the grains varied in number
      during regeneration of the liver, being more abundant on day 5 than on days 2 or
      10. The activity of [3H]-leucine incorporated into albumin synthesis, an
      indicator of translational activity, was higher on days 5 and 10 than on day 2
      and was highest on day 5. In conclusion, albumin synthesis varied during liver
      regeneration after partial hepatectomy, being reduced at the peak of cell
      proliferation on day 2 and being most active on day 5.

PMID- 9034934
TI  - Bone changes and mineral metabolism disorders in rats with experimental liver
      cirrhosis.
AB  - To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal
      liver disease, we developed a laboratory model in animals using carbon
      tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters
      in the model were measured. In rats with both chronic non-cirrhotic liver injury
      and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in
      controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the
      urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume
      was significantly correlated with both the serum albumin concentration and the
      number of goblet cells reflecting intestinal villous atrophy. The serum
      concentration of vitamin D metabolites was not correlated with bone volume. Whole
      body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats
      than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic
      rats was significantly lower than in controls. These data demonstrate that
      chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a
      combination of low bone formation rates and high resorption rates, that HOD
      begins at the stage of chronic non-cirrhotic liver injury, that bone volume in
      HOD parallels liver damage and that the principal pathogenesis of HOD seems to be
      intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while
      serum levels of vitamin D metabolites have little influence on the pathogenesis
      of HOD.

PMID- 9034935
TI  - Efficacy of ursodeoxycholic acid in combination with interferon-alpha in treating
      chronic hepatitis C: results of a long-term follow-up trial.
AB  - Ursodeoxycholic acid (UDCA) has recently been combined with interferon (IFN) in
      the treatment of individuals with chronic hepatitis C. However, whether its
      addition results in a long-term favourable response to IFN remains unclear. A
      prospective randomized trial of IFN alone versus IFN plus UDCA was therefore
      undertaken in 52 patients with chronic hepatitis C. All patients received a 24
      week course of IFN-alpha (6 x 10(6) U/day for 2 weeks and then three times a week
      for 22 weeks) and half also received UDCA (600 mg/day) with IFN and then alone
      for 48 additional weeks. Normalization of serum alanine transaminase (ALT)
      concentrations at 0, 24 and 48 weeks after cessation of IFN therapy was apparent
      in 77, 42 and 42% of patients in the IFN-alone group and in 77, 54 and 42% of
      patients in the IFN plus UDCA group, respectively. There was no significant
      difference between the two groups with regard to response rate to IFN and the
      addition of UDCA to IFN treatment had no significant effect on hepatitis C virus
      (HCV) viraemia. During the follow-up period, 10 of 20 patients with normal serum
      ALT at the end of IFN treatment relapsed in the IFN-alone group compared with 11
      of 20 patients in the IFN plus UDCA group. Among these relapsed patients, serum
      ALT concentration was significantly lower in the IFN plus UDCA group than in the
      IFN-alone group during the follow-up period. Twenty-four weeks after cessation of
      IFN therapy, the percentage of patients with HCV-RNA in their serum who showed a
      normalization of serum ALT concentrations was significantly higher in the IFN
      plus UDCA group than in the IFN-alone group (44 vs 6%). Thus, although the
      addition of UDCA was not associated with a favourable long-term response to HCV
      viraemia, it did reduce the risk and the severity of relapse following the
      cessation of IFN therapy.

PMID- 9034936
TI  - Case report: anti-proteinase 3 antibody activity in a patient with primary
      sclerosing cholangitis: clinical remission following ursodeoxycholic acid
      therapy.
AB  - Primary sclerosing cholangitis is rare among Chinese. We report on a 71 year old
      male patient who presented with clinical features consistent with the disorder.
      Subsequent investigations confirmed the diagnosis. The patient was found to have
      anti-neutrophil cytoplasmic antibodies with specificity against proteinase 3.
      Treatment with ursodeoxycholic acid resulted in clinical remission and
      disappearance of the antibodies.

PMID- 9034937
TI  - Changes in gastric HCO-3 secretory response to NG-nitro-L-arginine methyl ester
      in rats following repeated administration.
AB  - The effect of repeated administration of the nitric oxide synthase inhibitor NG
      nitro-L-arginine methyl ester (L-NAME) on gastric HCO-3 secretion was examined
      using ex vivo chambered stomachs of anaesthetized rats. Intravenous
      administration of L-NAME (5 mg/kg) increased gastric HCO-3 secretion with a
      concomitant rise in arterial blood pressure (BP). The HCO-3 stimulatory action of
      L-NAME diminished when rats were pretreated with L-NAME (20 mg/kg, p.o., twice
      daily) for 1 or 3 days and an inverse relationship was found between the degree
      of secretory stimulation and the period of pretreatment. The increased BP
      response to L-NAME was also significantly lessened following repeated
      pretreatment; basal BP showed a stepwise increase during repeated pretreatment
      and did not change at all in response to i.v. L-NAME after 3 days pretreatment.
      When delta HCO-3 output induced by i.v. L-NAME was plotted against delta BP (from
      basal values) during repeated pretreatment with L-NAME, a significant
      relationship was found between these two factors. The reduction in the HCO3
      secretory response to L-NAME was restored when animals were pretreated with L
      arginine (500 mg/kg, i.p., twice daily) together with L-NAME. However,
      prostaglandin E2 (300 micrograms/kg, i.v.) caused a gastric HCO-3 secretory
      response similar to L-NAME, regardless of whether rats had been pretreated with L
      NAME or not. In contrast, the attenuation by L-NAME of the acid (0.2 nmol/L HCl)
      induced gastric hyperaemic response was not influenced by repeated pretreatment
      with L-NAME. We conclude that repeated p.o. pretreatment with L-NAME reduces the
      HCO-3 stimulatory action of i.v. L-NAME and that this phenomenon may be explained
      by the lack of further elevation of BP in response to i.v. L-NAME following
      repeated pretreatment with this agent. Thus, the stimulation of HCO-3 secretion
      by i.v. L-NAME may be causally related with increased BP in response to this
      agent.

PMID- 9034938
TI  - Twice daily nizatidine or ranitidine is superior to once daily dosing in
      elevating 24 h intragastric pH in patients with duodenal ulcer disease.
AB  - The present study was performed in six asymptomatic patients with a history of
      resistant duodenal ulcers in whom 24 h intragastric pH, gastric juice pepsin and
      PGE2 concentrations, as well as serum gastrin concentrations, were measured. We
      wanted to compare the effects on these parameters of a single night time (q.h.s.)
      dose of nizatidine 300 mg (N1), nizatidine 300 mg b.i.d. (N2), ranitidine 300 mg
      q.h.s. (R1) or ranitidine 300 mg b.i.d. (R2) compared with placebo (P). During
      the night (22.00-08.00 h), all treatments gave a higher mean pH than P, but
      during the day (08.00-22.00 h) the mean pH was higher than P only for patients
      administered R2 and N2. Doubling the dose of nizatidine (N2 vs N1) or ranitidine
      (R2 vs R1) increased the mean daytime pH, but had no effect on night time pH. The
      daytime pepsin concentration was unaffected by H2-receptor antagonists, while
      night time pepsin was lower with R1 and R2, but not with N1 or N2. The night time
      gastrin concentration was unaffected by H2-receptor antagonists; doubling the
      dose of the H2-receptor antagonist (R2 vs R1 and N2 vs N1) increased daytime
      gastrin concentration. During the night, each treatment increased PGE2
      concentration by at least six-fold compared with P. Thus, where it is
      therapeutically indicated to achieve greater suppression of acid secretion,
      doubling the total daily dose by dosing with twice daily versus once daily night
      time nizatidine or ranitidine is efficacious.

PMID- 9034939
TI  - Pharmacokinetics of midazolam in Vietnamese subjects.
AB  - In order to examine the investigators' clinical suspicion that Vietnamese
      patients were more sensitive to the sedative effects of midazolam than were
      Caucasians, the pharmacokinetics of a single, weight-adjusted intravenous dose of
      midazolam (0.05 mg/kg) were compared in a group of healthy Caucasian and
      Vietnamese male volunteers. The Vietnamese group (n = 8) had a significantly
      lower height, lean body mass and mean weight (59.8 +/- 5.5 vs 72.1 +/- 8.1 kg,
      respectively) compared with the Caucasian group (n = 8). No significant
      differences were found between the Vietnamese and Caucasian groups with regard to
      distribution half-life of midazolam (8.38 +/- 13.1 vs 1.49 +/- 0.63 min,
      respectively), elimination half-life (2.49 +/- 1.80 vs 1.48 +/- 0.66 h,
      respectively), clearance (4.93 +/- 1.31 vs 5.90 +/- 2.12 mL/min per kg,
      respectively), steady state volume of distribution (0.863 +/- 0.497 vs 0.530 +/-
      0.132 L/kg, respectively) or percentage of unbound drug in plasma (4.89 +/- 0.74
      vs 4.11 +/- 1.08, respectively). This suggests that dosage of midazolam in
      Vietnamese should be based on total bodyweight. Two Vietnamese subjects who were
      brothers had marked elevation of distribution half-life and initial volume of
      distribution and lesser elevations in elimination half-life and volume of
      distribution at steady state. This suggests that the known subgroup of subjects
      who demonstrate dyshomogeneity in midazolam volume of distribution may be
      genetically determined.

PMID- 9034940
TI  - The effect of comorbidity on use of thrombolysis or aspirin in patients with
      acute myocardial infarction eligible for treatment.
AB  - OBJECTIVE: Growing evidence indicates that life-sustaining therapies for the
      treatment of acute myocardial infarction (AMI) are underused among patients
      eligible for therapy, including the elderly and women. We examined the effect of
      a patient's comorbidity burden on use of these highly effective therapies in
      eligible populations of individuals with AMI. DESIGN: Retrospective cohort
      design. SETTING AND PATIENTS: We reviewed the medical records of 2,409
      individuals at 37 Minnesota hospitals from October 1992 through July 1993 with an
      admission diagnosis of AMI, suspected AMI, or rule-out AMI, who met
      electrocardiographic, laboratory, and clinical criteria for AMI. MEASUREMENTS AND
      MAIN RESULTS: Using multivariate logistic regression models, we determined the
      association between a validated comorbidity measure and the proportion of
      eligible patients who received thrombolysis or aspirin. Controlling for other
      factors previously reported to influence rates of study treatment, the odds of
      receipt of thrombolysis among patients with severe comorbidity was 0.49 (95%
      confidence interval [CI] 0.27, 0.88) when compared with individuals without such
      limitation. Similarly, the odds of aspirin treatment among study patients with
      severe comorbidity was 0.46 (95% CI 0.30 0.72), compared with individuals without
      severe comorbidity. We did not distinguish any differences in patterns of
      treatment with either study treatment among patients with mild or moderate
      comorbidity when compared with individuals without any concomitant comorbidity.
      CONCLUSIONS: This study indicates that patients with severe mental and physical
      comorbidities are less likely to receive standard therapies for AMI recommended
      in national treatment guidelines.

PMID- 9034941
TI  - Correlates of controlled hypertension in indigent, inner-city hypertensive
      patients.
AB  - OBJECTIVE: To identify correlates of controlled hypertension in a largely
      minority population of treated hypertensive patients. DESIGN: Case-control study.
      SETTING: Urban, public hospital. PATIENTS: A consecutive sample of patients who
      were aware of their diagnosis of hypertension for at least 1 month and had
      previously filled an antihypertensive prescription. Control patients had a
      systolic blood pressure (SBP) < or = 140 mm Hg and diastolic blood pressure (DBP)
      < or = 90 mm Hg, and case patients had a SBP > or = 180 mm Hg or DBP > or = 110
      mm Hg. MEASUREMENTS AND MAIN RESULTS: Control subjects had a mean blood pressure
      (BP) of 130/80 mm Hg and case subjects had a mean BP of 193/106 mm Hg. Baseline
      demographic characteristics between the 88 case and the 133 control subjects were
      not significantly different. In a logistic regression model, after adjusting for
      age, gender, race, education, owning a telephone, and family income, controlled
      hypertension was associated with having a regular source of care (odds ratio [OR]
      7.93; 95% confidence interval [CI] 3.86, 16.29), having been to a doctor in the
      previous 6 months (OR 4.81; 1.14, 20.31), reporting that cost was not a deterrent
      to buying their antihypertensive medication (OR 3.63; 1.59, 8.28), and having
      insurance (OR 2.15; 1.02, 4.52). Being compliant with antihypertensive medication
      regimens was of borderline significance (OR 1.96; 0.99, 3.88). A secondary
      analysis found that patients with Medicaid coverage were significantly less
      likely than the uninsured to report cost as a barrier to purchasing
      antihypertensive medications and seeing a physician. CONCLUSIONS: The absence of
      out-of-pocket expenditures under Medicaid for medications and physician care may
      contribute significantly to BP control. Improved access to a regular source of
      care and increased sensitivity to medication costs for all patients may lead to
      improved BP control in an indigent, inner-city population.

PMID- 9034942
TI  - The treatment of chronic constipation in adults. A systematic review.
AB  - OBJECTIVE: To evaluate whether laxatives and fiber therapies improve symptoms and
      bowel movement frequency in adults with chronic constipation. DATA SOURCES:
      English language studies were identified from computerized MEDLINE (1966-1995).
      Biological Abstracts (1990-1995), and Micromedex searches; bibliographies;
      textbooks; laxative manufactures; and experts. STUDY SELECTION: Randomized trials
      of laxative or fiber therapies lasting more than 1 week that evaluated clinical
      outcomes in adults with chronic constipation. MEASUREMENTS AND MAIN RESULTS: Two
      independent reviewers appraised each trial's characteristics including
      methodologic quality. There were 36 trials involving 1,815 persons from a variety
      of settings including clinics, hospitals and nursing homes. Twenty-three trials
      were 1 month or less in duration. Several laxative and fiber preparations were
      evaluated. Twenty trials had a placebo, usual care, or discontinuation of
      laxative control group, and 16 directly compared different agents. Laxatives and
      fiber increased bowel movement frequency by an overall weighted average of 1.4
      (95% confidence interval [CI] 1.1-1.8) bowel movements per week. Fiber and bulk
      laxatives decreased abdominal pain and improved stool consistency compared with
      placebo. Most nonbulk laxative data concerning abdominal pain and stool
      consistency were inconclusive, though cisapride, lactulose, and lactitol improved
      consistency. Data concerning superiority of various treatments were inconclusive.
      No severe side effects for any of the therapies were reported. CONCLUSIONS: Both
      fiber and laxatives modestly improved bowel movement frequency in adults with
      chronic constipation. There was inadequate evidence to establish whether fiber
      was superior to laxatives or one laxative class was superior to another.

PMID- 9034943
TI  - Tuberculosis skin testing among homeless adults.
AB  - OBJECTIVE: To document the prevalence of tuberculosis (TB) skin test positivity
      among homeless adults in Los Angeles and determine whether certain
      characteristics of homelessness were risk factors for TB. DESIGN: Cross-sectional
      study. SETTING: Shelters, soup lines, and outdoor locations in the Skid Row and
      Westside areas of Los Angeles. PARTICIPANTS: A representative sample of 260
      homeless adults. MEASUREMENTS AND MAIN RESULTS: Tuberculosis tine test reactivity
      was measured. The overall prevalence of TB skin test positivity was 32%:40% in
      the inner-city Skid Row area and 14% in the suburban Westside area. Using
      multiple logistic regression, TB skin test positivity was found to be associated
      with living in crowded or potentially crowded shelter conditions, long-term
      homelessness, geographic area, history of a psychiatric hospitalization, and age.
      CONCLUSIONS: Homeless adults living in congested inner-city areas are at high
      risk of both latent and active TB. Endemic risk factors and limited access to
      medical care support the need for aggressive treatment of active TB cases and
      innovative programs to ensure completion of prophylactic regimens by homeless
      individuals with latent infection.

PMID- 9034944
TI  - Why do patients of female physicians have higher rates of breast and cervical
      cancer screening?
AB  - OBJECTIVE: Women are more likely to receive breast and cervical cancer screening
      if they see female physicians. We studied whether this is due to differences
      between male and female physicians, or to differences in their patients. SETTING:
      Large midwestern, independent practice association style of health plan. DESIGN:
      We surveyed male and female primary care physicians matched for age and specialty
      and a stratified random sample of three of each physician's women patients.
      Physicians reported on their practice setting, their attitudes and practices
      regarding prevention, and their comfort and skill with various examinations.
      Patients reported on their sociodemographic characteristics, their attitudes and
      practices regarding prevention, and their preferences for physician gender.
      Claims data were used to calculate mammography and Pap smear screening rates for
      the physicians. PARTICIPANTS: We studied 154 female and 190 male internists and
      family physicians and 794 of their patients. MEASUREMENTS AND MAIN RESULTS: We
      compared the responses of male and female physicians and their patients and used
      multivariable analysis to identify the patient and physician factors that
      accounted for the differences in screening rates between male and female
      physicians. Female physicians were more likely to ask new patients about
      components of prevention, to believe in the effectiveness of mammography, to feel
      more personal responsibility for ensuring that their patients received screening,
      and to report more comfort in performing Pap smears and breast examinations.
      Patients of female physicians were more educated and less likely to be married,
      but did not differ in other sociodemographic characteristics. They had similar
      attitudes and practices regarding prevention, except that patients of male
      physicians were more likely to smoke. Significantly more patients of female
      physicians preferred a female for some component of care. In multivariable
      analyses, practice organization, patient preference for a female physician, and
      prevention orientation of female physicians accounted for up to 40% of screening
      rate differences between female and male physicians for Pap smears, and 33% for
      mammography. CONCLUSIONS: Differences in beliefs of male and female physicians
      and patient preference for a female provider contribute independently to the
      higher rate of breast and cervical cancer screening by female physicians.

PMID- 9034945
TI  - Physicians' decisions to prescribe benzodiazepines for nervousness and insomnia.
AB  - OBJECTIVE: To assess the effects of particular clinical cues on decisions about
      prescribing benzodiazepines. DESIGN: A factorial survey based on social judgment
      theory. SETTING: A midwestern U.S. medical school. PARTICIPANTS: Physicians (n =
      115) recruited from the staff by invitation and interview. MEASUREMENTS AND MAIN
      RESULTS: Physicians indicated their level of agreement with prescribing a
      benzodiazepine for 24 hypothetical cases of nervousness and insomnia. The cases
      stemmed from the same scenario but varied systematically with regard to
      psychiatric diagnosis, recent ability to work, and long-term social stability. A
      fourth cue, called "health status," covertly depicted the presence or absence of
      three common alcohol-related medical problems. One fourth of the physicians
      agreed with prescribing for 15 or more cases, and 15% disagreed for all of them.
      Agreement was cumulative and least common for major depression, more common for
      adjustment disorder, and most common for generalized anxiety. Agreement with
      prescribing for cases with alcohol-related medical problems was 14% less than
      that for cases without them. Over half the physicians agreed with prescribing for
      4 or more of the 12 cases with alcohol-related medical problems. CONCLUSIONS:
      Prescribing decisions varied widely. Some physicians avoided benzodiazepines
      unnecessarily for some cases, while others agreed with prescribing for patients
      with a high probability of alcohol abuse. Blanket calls for more or less
      prescribing are overly simplistic; physicians should be able to recognize
      substance use disorders among anxious patients and make prescribing decisions
      based on relevant literature and clinical cues.

PMID- 9034946
TI  - The impact of role models on medical students.
AB  - OBJECTIVE: To explore the relationship between exposure to clinical role models
      during medical school and the students' choice of clinical field for residency
      training, and to estimate the strength of this association. DESIGN: Cross-section
      study. SETTING: McGill University School of Medicine, Montreal, Canada.
      PARTICIPANTS: Of the 146 graduating medical students in the class of 1995, 136
      participated. MEASUREMENTS AND MAIN RESULTS: Clinical field chosen by students
      for residency training and the students' assessment of their exposure to and
      interaction with physician role models were the main measurements. Ninety percent
      of graduating students had identified a role model or models during medical
      school. Personality, clinical skills and competence, and teaching ability were
      most important in the selection of a role model, while research achievements and
      academic position were least important. Odds ratios between interacting with
      "sufficient" role models in a given clinical field and choosing that same
      clinical field for residency were 12.8 for pediatrics, 5.1 for family medicine,
      4.7 for internal medicine, and 3.6 for surgery. Most students (63%) received
      career counseling and advice from their role models. CONCLUSIONS: Exposure to
      role models in a particular clinical field is strongly associated with medical
      students' choice of clinical field for residency training. Knowing which
      characteristics students look for in their role models should help identify the
      physicians who may be most influential in medical students' career choice.

PMID- 9034947
TI  - Predicting Clostridium difficile stool cytotoxin results in hospitalized patients
      with diarrhea.
AB  - OBJECTIVE: To validate a model for the prediction of Clostridium difficile
      cytotoxin assay results, and to identify a subgroup of patients with a very low
      likelihood of C. difficile-associated disease in whom the yield of routine
      cytotoxin testing is low. DESIGN: Prospective cohort study. Relevant clinical
      symptoms, signs, and antibiotic exposure were recorded before reporting of assay
      results. Each predictor was assigned a score based on regression coefficients,
      and patients were stratified according to their total score. SETTING: Two urban,
      tertiary care, university hospitals. PATIENTS: A total of 609 consecutive adult
      inpatients who received testing for C. difficile cytotoxin during a 3-month
      period in 1994. MEASUREMENTS AND MAIN RESULTS: The prevalence of positive
      cytotoxin assays was 8% in the validation set, compared with 14% in the
      derivation set. Defining patients without both prior antibiotic use and at least
      one symptom predictor (significant diarrhea or abdominal pain) as a low-risk
      subgroup, the misclassification rate was 2.8% (5/177) for assay results; of the
      five misclassified cases patients, only one was judged to have C. difficile
      associated disease. Use of this rule to identify low-risk patients could have
      potentially averted 29% of all cytotoxin assays. CONCLUSIONS: Patients without a
      history of antibiotic use and either significant diarrhea or abdominal pain are
      unlikely to have positive C. difficile cytotoxin assays and may not require
      cytotoxin testing.

PMID- 9034948
TI  - How do older persons define constipation? Implications for therapeutic
      management.
AB  - This study examined the relation between bowel-related symptoms and self-report
      of constipation in 10,875 subjects aged 60 years and over, who participated in
      the 1989 National Health Interview Survey. Subjects reporting constipation
      "always" or "mostly" over the past 12 months (n = 594) were compared with those
      who reported never having the symptom (n = 4,192). Straining (adjusted odds ratio
      66.7; 95% confidence interval 31.5, 142.4) and hard bowel movements (25.6; 16.7,
      38.7) were most strongly associated with self-report of constipation. These
      findings suggest that treatment for constipation in the older population should
      be directed as much or more at facilitating comfortable rectal evacuation, as
      increasing bowel movement frequency.

PMID- 9034949
TI  - Assessing patients' expectations in ambulatory medical practice. Does the
      measurement approach make a difference?
AB  - To compare three different approaches to the measurement of patients'
      expectations for care, we conducted a randomized controlled trial. Medical
      outpatients (n = 318) of a small (six-physician), single-specialty (internal
      medicine), academically affiliated private practice in Sacramento, California,
      were contacted by telephone the night before a scheduled office visit and
      enrolled over a 5-month period in early 1994. Patients were randomly assigned to
      receive: (1) a self-administered, structured, previsit questionnaire combined
      with a postvisit questionnaire; (2) an interviewer-administered, semistructured,
      previsit interview combined with a postvisit questionnaire; or (3) a postvisit
      questionnaire only. We assessed the number and content of patients' expectations
      by previsit questionnaire versus interview; the interaction between
      sociodemographic characteristics and survey method in predicting number of
      reported expectations; the effect of unfulfilled expectations elicited by
      questionnaire and interview on visit satisfaction; and the effect of unfulfilled
      expectations elicited directly and indirectly on visit satisfaction. Patients
      reported more expectations by structured questionnaire than semistructured
      interview (median 12 vs 3, p = .0001). Although there was no main effect of
      sociodemographic characteristics on expectations, nonwhite patients reported more
      expectations than white patients by questionnaire and fewer by interview. The
      number of interventions desired before the visit but not received (indirectly
      reported unfulfilled expectations) was associated with lower visit satisfaction
      regardless of whether a questionnaire or interview was used to elicit previsit
      expectations (p value for the interaction between number of expectations and
      survey method, > .20). Having more indirectly reported unfulfilled expectations
      was significantly associated with lower visit satisfaction even after controlling
      for the number of directly reported unfulfilled expectations (p = .021), but the
      incremental change in classification accuracy was small (increase in receiver
      operating characteristic curve area, 3%). In conclusion, studies of patients'
      expectations for care must content with a substantial "method effect." In this
      study from a single group practice, patients checked off more expectations using
      a structured questionnaire than they disclosed in a semistructured interview, but
      both formats predicted visit satisfaction. Asking patients about interventions
      received in relation to their previsit expectations added little to simply asking
      them directly about omitted care. The interaction of survey method with ethnicity
      and other sociodemographic characteristics requires further study.

PMID- 9034950
TI  - Do comorbidities influence the treatment of myocardial infarction?

PMID- 9034951
TI  - Constipation happens.

PMID- 9034952
TI  - Honor our role models.

PMID- 9034953
TI  - Fossil clavicle of a middle Pleistocene hominid from the Central Narmada Valley,
      India.
AB  - The discovery of a Middle Pleistocene hominid clavicle is reported here. This
      discovery is particularly important because clavicles are hitherto unrepresented
      in the fossil record of Asia. The Narmada clavicle comes from the Boulder
      Conglomerate horizon at Hathnora near Hoshangabad in the Central Narmada Valley.
      This is the same deposit that previously yielded the Homo erectus/archaic Homo
      sapiens partial cranium, which has recently been dated to between 0.2 and 0.7 ma
      (million years ago). The specimen has some unusual morphology and is a very short
      and robust bone, far shorter than even the early African Homo erectus clavicles.
      It is about the size that would be expected in an adult human pygmy. This
      discovery reopens the debate on the taxonomic position of the Narmada hominid in
      human ancestry.

PMID- 9034954
TI  - A reappraisal of early hominid phylogeny.
AB  - We report here on the results of a new cladistic analysis of early hominid
      relationships. Ingroup taxa included Australopithecus afarensis, Australopithecus
      africanus, Australopithecus aethiopicus, Australopithecus robustus,
      Australopithecus boisei, Homo habilis, Homo rudolfensis, Homo ergaster and Homo
      sapiens. Outgroup taxa included Pan troglodytes and Gorilla gorilla. Sixty
      craniodental characters were selected for analysis. These were drawn from the
      trait lists of other studies and our own observations. Eight parsimony analyses
      were performed that differed with respect to the number of characters examined
      and the manner in which the characters were treated. Seven employed ordered
      characters, and included analyses in which (1) taxa that were variable with
      respect to a character were coded as having an intermediate state, (2) characters
      with variable states in any taxon were excluded; (3) a variable taxon was coded
      as having the state exhibited by the majority of its hypodigm, (4) variable taxa
      were coded as missing data for that character, (5) some characters were
      considered irreversible, (6) masticatory characters were excluded, and (7)
      characters whose states were unknown in some taxa were excluded. In the final
      analysis, (8) all characters were unordered. All analyses were performed using
      PAUP 3.0s. Despite the fact that the eight analyses differed with respect to
      methodology, they produced several consistent results. All agreed that the
      "robust" australopithecines form a clade, A. afarensis is the sister taxon of all
      other hominids, and the genus Australopithecus, as conventionally defined, is
      paraphyletic. All eight also supported trees in which A. africanus is the sister
      taxon of a joint Homo+ "robust" clade, although in one analysis an equally
      parsimonious topology found A. africanus to be the sister of the "robust"
      species. In most analyses, the relationships of A. africanus and H. habilis were
      unstable, in the sense that their positions vary in trees that are marginally
      less parsimonious than the favored one. Trees in which "robust"
      australopithecines are paraphyletic were found to be extremely unparsimonious.

PMID- 9034955
TI  - ESR analysis of teeth from the palaeoanthropological site of Zhoukoudian, China.
AB  - An ESR dating study on teeth collected from layers 3, 6/7 and 10 at Locality 1,
      Zhoukoudian provides results that are in general agreement with an earlier multi
      dating study and confirm an age range of 300-550 ka for the Homo erectus remains
      in the Peking Man Cave. Uncertainties due to U-uptake and the external gamma dose
      rates do not allow very precise age estimates for the respective layers.

PMID- 9034956
TI  - New Miocene fossil ape locality, Dangar, Hari-Talyangar region, Siwaliks,
      northern India.

PMID- 9034957
TI  - Assessing the pelvis of AL 288-1: a reply to Wood and Quinney.

PMID- 9034959
TI  - Effect of SR 27417, a novel PAF antagonist on antigen-induced hypotension in the
      rat.
AB  - SR 27417, a potent PAF receptor antagonist, inhibited in a dose-dependent manner
      the hypotensive effect of PAF in rats. It protected rats with an ED50 value of 6
      +/- 2 micrograms/kg (n = 6), when given i.v., 1 min before PAF administration.
      After i.v. administration, SR 27417 exhibited extended duration of action, a
      significant protective effect was observed up to 48 h after the administration.
      After i.v. injection, SR 27417 (0.3, 1 and 3 mg/kg) afforded dose-dependent
      protection of actively sensitized rats against ovalbumin-induced hypotension but
      also totally reversed established antigen-induced hypotension. These results
      therefore confirm that PAF plays a major role in anaphylactic shock and suggest
      that SR 27417 may be an effective prophylactic as well as a potent curative drug
      in this pathology.

PMID- 9034958
TI  - Modulation of the cytosolic Ca++ concentration by alkylphospho-L-serine analogs:
      relation to their antiproliferative action.
AB  - Antiproliferative alkyllysophospholipid (ALP) analogs produced multiple effects
      on the cytosolic Ca++ concentration ([Ca++]i) in an immortalized human breast
      epithelial cell line (H 184). The addition of small concentrations resulted in a
      short transient [Ca++]i response. With higher concentrations the transient rise
      was followed by a sustained increase. Pretreatment of cells with the ALP analogs
      for two minutes inhibited the transient [Ca++] response. Increases in [Ca++]i and
      inhibition of the transient increase were studied in relation to the dose and
      structure of several ALP analogs. In a series of alkylphospho-L-serine analogs
      with different lengths of the alkyl chain we found different dependencies of the
      stimulatory and inhibitory effects on the dose and the structure. The ability to
      increase [Ca++]i is absent with the C14 and C15 analogs, is low with the C16 and
      high with the C18 analog. With the exception of the C12 analog, a dose-related
      inhibition was observed with all derivatives but the effective concentrations
      differed very strongly and the maximal potency was reached with the C15 and C16
      analogs. The antiproliferative action seems to correlate rather with the potency
      to inhibit the transient [Ca++]i response than with its stimulation.

PMID- 9034960
TI  - Structure-activity relationships in platelet activating factor. 9. From PAF
      antagonism to PLA2 inhibition.
AB  - Many important mediators of inflammation result from the liberation of free
      arachidonic acid from phospholipid pools, which arise from the action of
      phospholipase A2 (PLA2). Therefore the inhibition of this enzyme would be an
      important treatment in many inflammatory disease states. Starting from a series
      of compounds which are known as PAF-antagonists, we have synthesized new
      molecules. These new compounds inhibited various secretory PLA2s, with IC50's in
      the mumol range. This allowed us to analyze the structure-activity relationships
      for PLA2 inhibition. The results showed that inhibition of secretory PLA2 depends
      on the length of the alkyl chain, with an optimum for 13 to 17 carbons, which is
      in agreement with X-ray crystallographic and nuclear magnetic resonance (NMR)
      studies on the active site of PLA2s, and that a free nitrogen on the piperazine
      ring is required to ensure a good inhibitory potency.

PMID- 9034962
TI  - Design and modeling of new platelet-activating factor antagonists. 3. Relative
      importance of hydrophobicity and electronic distribution in piperazinic series.
AB  - Extensive analysis of results obtained in earlier publications (Lamouri et al.
      (1993); Tavet et al. (1996) led us to reexamine our interpretations and
      conclusions about hydrophobic and electronic distribution effects. In terms of
      hydrophobicity balance, a bilinear regression has been derived between
      lipophilicity of the appendix in position-2, f(Z), versus anti-aggregant activity
      for 45 homogeneous compounds including data from both papers (Parts 1 and 2).
      These features reinforce the conclusion that the kinetic phase in the
      experimental medium is probably determinant. Consequently, the role of electronic
      distribution is preponderant at the level of the receptor. Two specific studies
      demonstrated that decrease of negative electrostatic potential effects of the
      largest "cache-oreilles' system lowered the anti-aggregant activity (comparison
      of compounds 1f, 2, 3 and 4), on one hand and, on the other hand, the combined
      effect of phenyl groups created negative wells, as observed there with a diphenyl
      methyl moiety, instead of an usual trimethoxybenzoyl function (comparison of
      compounds 8 and 10). It was clearly demonstrated that this moiety does not work
      by means of a hydrophobic anchorage: comparison of compounds 9, 10 and 11.

PMID- 9034961
TI  - Design and modeling of new platelet-activating factor antagonists. 2. Synthesis
      and biological activity of 1,4-bis-(3',4',5'-trimethoxybenzoyl)-2-alkyl and 2
      alkyloxymethylpiperazines.
AB  - In the continuation of our investigations on the structure of platelet-activating
      factor (PAF)-receptor, 25 additional 2-substituted 1,4-bis-(poly- and mono
      methoxybenzoyl)-piperazines were synthesized and their in vitro biological
      activities measured. Substituent at position 2 is representative of the classical
      balance lipophilicity/hydrophilicity, i.e. alkyl, phenylalkyl, alkoxy and
      polyalkoxy groups. A potent PAF-induced platelet aggregation inhibitory activity
      measured in PRP medium is obtained with 5c, IC50 = 6 x 10(-8) M, which displaces
      the [3H]PAF from platelet membrane with an EC50 = 6 x 10(-8) M, and compound 4
      presents an EC50 of 3 x 10(-8) M. Examination of structure-activity relationships
      shows that molecules bearing a hydrophilic or slightly hydrophobic appendix in
      position-2 are still potent; their IC50 being included between 10(-6) and 10(-7)
      M. After quantitative analysis, it seems that in PRP medium, the role of serum
      albumin must be taken into account instead of a pure hydrophobic interaction of
      the appendix Z into the receptor. The role of the methoxy groups in producing a
      potent antagonistic activity is demonstrated by syntheses of several 2
      octylpiperazine analogs. These specific features will be quantitatively analysed
      in the following related publication (part 3).

PMID- 9034963
TI  - Phospholipase D hydrolysis of plasmalogen and diacyl ethanolamine
      phosphoglycerides by protein kinase C dependent and independent mechanisms.
AB  - Ethanolamine phosphoglycerides (EPG) are potential sources of lipid second
      messengers in signal transduction pathways. We investigated EPG turnover,
      including both 1-alkenyl-2-acyl- (plasmalogen) and diacyl-classes, in response to
      stimulation of protein kinase C (PKC) by phorbol ester (4 beta-12-O
      tetradecanoylphorbol-13-acetate (TPA)) in cultured C6 rat glioma cells. Release
      of ethanolamine to the medium from EPG prelabeled with [14C]ethanolamine
      indicated that initial (< 60 min) TPA-stimulated hydrolysis of EPG was
      predominantly by phospholipase D (PLD). Effects of TPA on PLD activity
      specifically with EPG was confirmed using trans-phosphatidylation by incubating
      cells prelabeled with [14C]eicosapentaenoic acid (20:5n-3) with 100 nM TPA and 1%
      butanol. Analysis of acid-labile phosphatidylbutanol and remaining EPG showed
      utilization of both plasmalogen and non-plasmalogen EPG. Staurosporine (STS)
      inhibited PKC at 200-500 nM but stimulated PLD activity 2-fold at > or = 1
      microM. However, STS did not eliminate all TPA-stimulated PLD activity, even when
      PKC was > 98% inhibited. Bis-indolylmaleimide (BIM) fully inhibited PKC activity
      but had no independent effects on PLD and did not completely inhibit TPA- or
      bryostatin-stimulated PLD activity. Down-regulation of PKC by chronic exposure to
      TPA eliminated stimulation of PLD by TPA but not by STS. Thus, PLD hydrolysis of
      both plasmalogen and diacyl-EPG is a source of potential lipid second messengers
      in C6 glioma cells. PLD is stimulated by activation of PKC and by PKC-independent
      action of STS. Further, the possibility that TPA may also elicit responses
      through a mechanism independent of PKC activity is suggested.

PMID- 9034964
TI  - Modulation of phospholipase D stimulation in c-src transfected mesangial cells.
AB  - Stimulation of rat mesangial cells with platelet-derived growth factor BB (PDGF
      BB) enhanced phospholipase D (PLD) activity in a concentration dependent manner.
      Mesangial cells overexpressing the tyrosine kinase pp60c-src (c-Src) were used to
      determine the effect of this non transforming protooncogene on PLD activation.
      Overexpression of c-Src interfered with PDGF-BB-mediated activation of PLD. This
      modulation was dependent on the tyrosine kinase activity of c-Src, since
      overexpression of tyrosine kinase-negative mutants of c-Src did not affect PLD
      activation. No effect of c-Src overexpression was observed, when PLD was
      activated by ATP or guanosine 5'-3-O-(thio)triphosphate (GTP gamma S). The
      results indicate that the tyrosine kinase c-Src specifically interfered with PDGF
      mediated but not with ATP- or GTP gamma S-mediated PLD activation.

PMID- 9034965
TI  - Preventive effects of two PAF-antagonists, PMS 536 and PMS 549, on cyclosporin
      induced LLC-PK1 oxidative injury.
AB  - The present study was undertaken to evaluate the effects of platelet activating
      factor (PAF) antagonists, PMS 536 and PMS 549, on LLC-PK1 toxicity induced by
      Cyclosporin A (CsA). The LLC-PK1 cell line was used as an in vitro model. CsA
      cytotoxicity was determined in relation with ATP content. Alkaline phosphatase
      and N-acetyl-beta-glucosaminidase activities, which are directly correlated with
      tubular cell damage, were used as markers for renal injury. CsA alone provoked in
      the LLC-PK1 cell line a marked decrease in cell viability (55%) and membrane
      integrity (56%), and a significant increase in AP and NAG activities and in
      oxidized glutathione level. The ATP decrease and the ADP increase, resulting in a
      decline of the ATP/ADP ratio, is indicative of an anoxic energy charge. Co
      treatment with CsA plus PMS 536 or PMS 549 resulted in a minor decrease in cell
      viability and in significant membrane integrity recovery. Moreover, the ATP
      depletion and the increase in ATP metabolites, hypoxanthine and uric acid induced
      by CsA were strongly prevented by PAF antagonists. In contrast, GSSG level
      remained high as in CsA-treated cells, but GSH level was in the range of
      controls. Our results suggest that both PAF antagonists attenuate CsA oxidative
      injury and prevent energy metabolism disturbances probably by maintaining cell
      integrity. The lipophilicity of both molecules may be responsible for membrane
      stabilization and may confer the protective effects observed in energy
      metabolism. The results obtained with PMS 536 and PMS 549 are indicative of
      interactions between PAF and CsA in renal injury and suggest the therapeutic
      potential of these PAF-antagonists against CsA-induced nephrotoxicity.

PMID- 9034966
TI  - The dawn of a new era.
AB  - This paper reviews the scientific events culminating in the fluoridation of
      communal water supplies. Dental and medical studies completed by 1942 had
      established the safety and benefits of exposure to drinking water naturally
      containing fluoride. Researchers and public health workers concluded that it was
      possible to test the hypothesis that the dental benefits attained where fluoride
      levels around 1 ppm occurred naturally in drinking water could be safely
      replicated in low-fluoride areas by raising the level to this optimal
      concentration. Grand Rapids became the first test site and by the time the
      demonstration ended in 1959, around 40 million people in about 2,000 communities
      already were drinking water with fluoride levels that had been adjusted to
      optimal. The success of fluoridation brought the dawn of the era of caries
      control and created great opportunities for research and public health.

PMID- 9034967
TI  - Fluoridation and the private practice of dentistry.
AB  - Water fluoridation holds an important place in the history of Grand Rapids. This
      paper recounts the firsthand professional experiences of a dentist before and
      after he joined his father's established dental practice in Grand Rapids, only
      two years after fluoridation of the city's water supply began. The benefits of
      water fluoridation are documented through a review of office records. The
      prevalence of dental caries in patients who were born in Grand Rapids after water
      fluoridation began is low, and no case of a missing first permanent molar was
      found. Quadrant dentistry is no longer practiced. Children of parents born in
      Grand Rapids after the start of water fluoridation experience less decay than
      their parents, suggesting that factors in addition to water fluoridation have
      played a role in the downward trends in caries. The complete destruction of
      mouths of patients seen in this practice 50 years ago no longer happens,
      providing evidence of the benefits of water fluoridation, the most important
      advance ever in dentistry.

PMID- 9034968
TI  - Status and strategic plans for fluoridation: Centers for Disease Control and
      Prevention perspective.
AB  - This paper summarizes the current status of water fluoridation in the United
      States and discusses the strategic plan developed by the Division of Oral Health
      (DOH), Centers for Disease Control and Prevention (CDC) to meet the Healthy
      People 2000 fluoridation objective. This objective proposes to: "Increase to a
      least 75 percent the proportion of people served by community water systems
      providing optimal levels of fluoride (baseline: 62% in 1989)." The CDC strategic
      plan defines the nature of the problem with attainment of this objective, sets
      CDC priorities, and establishes six major components for future action: (1)
      assessment, evaluation and surveillance; (2) consultation; (3) state and regional
      efforts; (4) professional education and involvement; (5) public education; and
      (6) quality assurance. Actions in each of the components of the plan to help in
      the attainment of priorities are detailed. Finally, the broader picture of the
      federal role in a national fluoride plan is discussed.

PMID- 9034969
TI  - The fluoridation war: a scientific dispute or a religious argument?
AB  - Communal water fluoridation is not considered controversial by the vast majority
      of the scientific community; however, politically it has persisted as an issue
      that many legislators and community leaders have avoided because of an aura of
      dispute, it has been a battleground for vigorous opposition by a very small but
      outspoken minority who have fought it with the dedication of religious zealots.
      This paper reviews the nature of the opposition, who they are, the broad thrust
      of their arguments, some of the specific issues they have raised, and their
      techniques.

PMID- 9034970
TI  - The effectiveness of community water fluoridation in the United States.
AB  - Grand Rapids, the first city in the world to implement controlled water
      fluoridation, has served as a model for thousands of other communities.
      Fluoridation is one of the greatest public health and disease-preventive measures
      of all time. Its advantages include effectiveness for all, ease of delivery,
      safety, equity, and low cost. Today, nearly 56 percent of the US population lives
      in fluoridated communities (62% of those on central water supplies). Previously
      observed caries reductions of one-half to two-thirds are no longer attainable in
      the United States because other fluoride methods and products have reduced the
      caries prevalence in all areas, thus diluting the measurement of effectiveness,
      and because benefits of fluoridation are dispersed in many ways to persons in
      nonfluoridated areas. Water fluoridation itself, however, remains as effective as
      it ever was among groups at high risk to dental caries. Contrary to early beliefs
      that stressed the importance of preeruptive fluoride exposure, fluoridation also
      provides an important source of topical fluoride and facilitates
      remineralization. Although data on effectiveness and safety are compelling,
      future progress of water fluoridation will be affected by economic, political,
      and public perception factors.

PMID- 9034971
TI  - The results of water fluoridation in Ireland.
AB  - The visit of Dr. Trendley Dean to Dublin in the mid-1950s helped accelerate the
      decision to introduce water fluoridation as a public health measure in the
      prevention of caries in the Republic of Ireland. A challenge to the
      constitutional validity of the Health (Fluoridation of Water Supplies) Act 1960
      failed and in 1964 the water supplies of Dublin city were fluoridated. Over the
      next seven to eight years all the major urban communities in the Republic of
      Ireland were fluoridated. Currently, 67 percent of the 3.5 million people in the
      country reside in fluoridated communities. Studies conducted over the last 20
      years show that residents of fluoridated communities have better dental health
      than those in nonfluoridated communities--the mean dmft is lower in children and
      the number of natural teeth present in adults is higher.

PMID- 9034972
TI  - Water fluoridation results in Basel since 1962: health and political
      implications.
AB  - The population of the canton Basel-City has been provided with fluoridated water
      since May 1962. This paper presents a summary of basic findings from evaluations
      of this public health intervention. Standard methods were used for assessing
      dental caries, enamel fluorosis, urinary fluoride, and other data. Caries
      prevalence of schoolchildren declined until 1977 because of water fluoridation,
      after which it continued to decline until the late 1980s due to reasons other
      than water fluoridation. Caries prevalence in Basel was at least as low as in
      those other parts of Switzerland where either school-based dental health
      education programs or comprehensive salt fluoridation programs had been
      implemented for many years. Enamel fluorosis was seen in 38 percent of the
      children, similar to regions with comprehensive salt fluoridation, but higher
      than in low-fluoride regions. Overlap of salt and water fluoridation in families
      consuming both fluoridated water and fluoridated salt has occurred, but has not
      resulted in problems. Fluoride concentrations (close to, but mostly below 1.0
      ppm) and excretions (0.45-0.80 mg F per day in children, around 1 mg in adults)
      corresponded to expected levels. Statistics from both the School Dental Service
      and the Public Dental Clinic indicate a dramatic reduction in the amount of
      conservation dentistry being done and, in adults, prosthetic services. Political
      steps to remove water fluoridation were taken in 1976, 1982, 1989, and 1993, but
      have not been successful. Water fluoridation has resulted in the expected benefit
      and continues to exist beside salt fluoridation used in the other cantons of
      Switzerland.

PMID- 9034973
TI  - From the art of filling teeth to the science of dental caries prevention: a
      personal review.
AB  - The journey from the art of filling teeth to the science of prevention is
      reviewed. First, a private winding road is described that produced some new
      methods of value in risk assessment, treatment of the causes of dental caries,
      and prevention of the disease. The description illustrates the importance of
      monitoring the effects of different measures. Next, the new knowledge and methods
      that form the primary basis of prevention on a large scale are reviewed. They
      represent a golden era in caries research and form a solid ground for the
      prevention of dental caries and for the treatment of the causes of disease. The
      prevalence and incidence of dental caries has fallen not only among
      schoolchildren, but also among adults in developed countries. Improvement in
      dental health is due to the successful application of new knowledge-it has not
      happened by chance. New or improved opportunities for prevention could lead to a
      further reduction in dental caries. The problem is to find ways to stimulate both
      dentists and patients to use them. Finally, the next part of the journey is
      discussed. In some countries the journey probably will be an uphill struggle; in
      others, it could be fairly undulating, eventually leading to further declines in
      dental caries.

PMID- 9034974
TI  - And the next 50 years? The future of recombinant DNA technology in oral medicine.
AB  - As we celebrate this spectacular 50th anniversary, fluoridation continues to be
      the most effective public health strategy to reduce the disease burden of dental
      caries. Curiously, while H. Trendley Dean and his colleagues at the National
      Institutes of Health were investigating the effects of fluoride on tooth enamel
      in the mid-1930s, two young boys, one in London and the other in Chicago, were
      growing up to become the catalysts for another "biological revolution." These two
      very talented individuals, James Watson and Francis Crick, would later meet by
      accident at Cambridge and produce their seminal discovery published in April 1953
      as a letter in Nature, a one-page article provoking an international scientific
      adventure to understand living organisms in terms of the structure and function
      of deoxyribonucleic acid (DNA), a universal genetic code and a rationale for the
      applications of recombinant DNA technology (rDNA) in fields as diverse as
      agriculture, energy, industry, and health. As we now reflect upon the triumphs
      from fluoridation and ponder the next 50 years and the complexities of
      craniofacial, oral, and dental diseases, it becomes increasingly evident that
      recombinant DNA technology coupled with health promotion, disease prevention, and
      public education offers the promise for remarkable advances in prevention,
      diagnosis, and therapeutics in oral medicine.

PMID- 9034975
TI  - The dental curriculum: what should be new in the 21st century?
AB  - Dental education is at a critical juncture. The success of water fluoridation has
      reduced the caries burden of Americans and, consequently, has raised questions
      about the disproportionate technical emphasis on treating the sequelae of caries
      in US dental schools. Additionally, several powerful external factors-such as
      changing demographics, advances in biological science, fundamental changes in our
      health care delivery system, and a modest US economy-are forcing dental educators
      to question the appropriateness of retaining the current dental curriculum into
      the 21st century. The author considers these factors, suggests what type of
      dentist will be needed by society in approximately 20 years, and concludes that
      today's dental educational system is inadequate to produce such a dentist.
      Several elements, in addition to technical excellence, are required for the
      dental curriculum, including major changes in pedagogy, relevant science
      training, practical fluency in medicine, an increased mix of stomatologic skills,
      and broader contact with other health care providers.

PMID- 9034976
TI  - A pragmatic primer ... lessons from natural science for the profession of
      dentistry.
AB  - Artificially supplementing our community water supplies with optimal amounts of
      fluoride to gain the benefits of a significant reduction in dental caries is a
      lesson we have learned from natural science, a lesson from nature we have
      appropriated for culture- and a very pragmatic lesson. Today, we have discovered
      through science additional principles of nature that can be instructive and that
      can be appropriated for the profession of dentistry's benefit. This paper reviews
      five principles of natural science and derives lessons for the profession from
      these principles. The principles include natural selection, environmental change,
      form follows function, symbiosis, and entropy. Lessons derived from these
      principles of natural science are, respectively: survival and thriving of the
      profession are dependent upon the environment; the status quo will not be
      maintained-the profession must acknowledge, encourage, and celebrate change; the
      form the profession assumes must be consistent with its function of serving
      society; the profession must acknowledge the interdependence and reciprocity
      existing in its relationship with society; and the profession must continuously,
      energetically, and creatively reconstruct and renew itself. The challenge before
      us is to transform dentistry into a profession that continuously anticipates
      environmental changes by energetically creating new forms or structures that will
      result in more effective fulfillment of our function: gaining the benefits of
      oral health for society.

PMID- 9034977
TI  - Prescribing nonsteroidal antiinflammatory drugs--what's new?

PMID- 9034978
TI  - New perspectives for nonsteroidal antiinflammatory therapy.

PMID- 9034979
TI  - Remitting distal extremity swelling with pitting edema: a distinct syndrome or a
      clinical feature of different inflammatory rheumatic diseases?

PMID- 9034980
TI  - HLA-DR restrictive supertypes dominate promiscuous T cell recognition:
      association of multiple HLA-DR molecules with susceptibility to autoimmune
      diseases.
AB  - The association of individual autoimmune diseases with multiple HLA molecules has
      remained an enigma. That T cells can recognize the same peptide presented by
      several different HLA-DR alleles (i.e., promiscuous recognition) has been well
      documented. To explain this, we propose the "DR restrictive supertype pattern (DR
      RSP)" hypothesis. We focus on the known amino acid polymorphisms at positions
      beta 70, beta 71, and beta 74 located within pocket 4 of the DR molecule and
      their potential influence on promiscuous T cell recognition. We have shown that
      HLA-DR alleles may be grouped, on the basis of their polymorphisms at these
      positions, into at least 6 sets of DR alleles, 4 of which share, respectively,
      one of the RSP: A (Q/RR/KA), D (DE/R[K]A/L), E (Q/RRE), or R (QKR/Q) and 2 of
      which share the restrictive patterns Q (DRQ) or a (QAA). Most of the RSP have
      been shown to be associated with promiscuous T cell recognition of antigenic
      peptides. We also provide a rationale on how different DR alleles, exhibiting a
      particular RSP, might be capable of binding an antigenic peptide and presenting
      it, in a promiscuous fashion, to peptide-specific T cells. By identifying these
      RSP represented by DR alleles that have been clinically associated with certain
      autoimmune disease, we also extend the DR RSP hypothesis to account for the
      association of certain autoimmune diseases with multiple HLA-DR alleles.

PMID- 9034981
TI  - Plasma tetranectin levels and disease activity in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: We investigated alterations of levels of plasma tetranectin, a new
      regulator of plasminogen activation, in patients with rheumatoid arthritis (RA)
      in relation to disease activity and other fibrinolytic variables. METHODS:
      Tetranectin (TN), tissue-type plasminogen activator (t-PA), and plasminogen
      activator inhibitor (PAI-1) were quantitatively assessed (ELISA) in plasma of 41
      patients with RA and 30 healthy subjects, alpha 2-Antiplasmin activity was
      assessed by the amidolytic method. Disease activity was determined as a composite
      Stoke Index, which measures inflammatory processes in RA. Patients were divided
      into 3 groups according to Stoke Index score of disease activity: A, minimal
      mild, 1-7: B. moderate. 8-11: C. severe. 12-17. RESULTS: Plasma TN in patients
      was significantly lower compared to that of healthy subjects [9.11 (4.97-13.49)
      mg/l, 12.05 (9.50-13.60) mg/l, median (range), respectively; p = 0.0001]. TN
      decreases with the increase of disease activity from group to group. A
      significant negative correlation between TN and Stoke Index. C-reactive protein
      and erythrocyte sedimentation rate was found (rs = -0.49, p = 0.0012; rs = -0.44,
      p = 0.0044; rs = -0.37, p = 0.016, respectively). alpha 2-Antiplasmin activity
      was elevated in patients compared to healthy subjects [105.0% (53.0-146.0), 70.6%
      (48.2-124.0), median (range), respectively; p = 0.0001], showing a negative
      correlation with Stoke Index (rs = -0.38, p = 0.0139). The close positive
      correlation of TN with alpha 2-antiplasmin (rs = 0.66, p = 0.0001) and the
      absence of correlation with t-PA and PAI-1 were explained by the involvement of
      TN and alpha 2-antiplasmin in localized rather than in systemic fibrinolysis.
      CONCLUSION: Our findings suggest TN plays a role in the pathophysiology of RA and
      point to the usefulness of TN assessment as a specific fibrinolytic marker in the
      evaluation of disease activity in patients with RA. The role of TN in the
      intraarticular regulation of fibrinolysis, important for the expansion of pannus,
      tissue remodeling and angiogenesis, is discussed.

PMID- 9034982
TI  - IgA rheumatoid factor correlates with changes in B and T lymphocyte subsets and
      disease manifestations in rheumatoid arthritis.
AB  - OBJECTIVE: To analyze the relationship between lymphocyte subsets, different
      rheumatoid factor (RF) isotypes, and clinical features in patients with
      rheumatoid arthritis (RA). METHODS: Patients with established RA (n = 95) were
      examined clinically and blood samples were collected for measurements of RF by
      ELISA and for analysis of lymphocyte subsets by flow cytometry. RESULTS: IgA RF
      positive patients had more severe disease and higher prevalence of extraarticular
      manifestations than the other patients. Patients with elevated IgA RF had a
      higher percentage of CD5+ B cells and of CD4+CD45RO+ T cells compared to the
      other patients with RA or controls. High percentage of CD4+CD45RO+ T cells was
      also significantly associated with extraarticular manifestations. Patients with
      the sicca syndrome had significantly higher ratio of CD5+ B cells than patients
      without or with other types of extraarticular manifestations. CONCLUSION:
      Different disease manifestations in RA may be associated not only with certain RF
      isotypes and RF isotype combinations but also with changes in lymphocyte subsets
      in the blood. The relative increase of CD4+CD45RO+ T cells in the blood of IgA RF
      positive patients with RA might reflect preferential recruitment of CD8+CD45RO+ T
      cells to inflammatory sites.

PMID- 9034983
TI  - A hidden immunoglobulin G2 in patients with rheumatoid arthritis detected by
      nuclear magnetic resonance.
AB  - OBJECTIVE: The ratios of immunoglobulin (Ig) G1 and IgG2 in patients with
      rheumatoid arthritis (RA) were examined by nuclear magnetic resonance (NMR) and
      the results were compared to data obtained by ELISA. METHODS: The IgG of 11
      patients with RA were prepared with a DE-52 column and the specific signals for
      IgG1 and IgG2 were measured by NMR. The ratios of IgG1 and IgG2 were determined
      by the intensity of this signal. The samples were also measured by ELISA.
      RESULTS: The ratios of IgG2 in patients with RA measured by NMR were increased
      significantly compared to controls. However, there were no significant
      differences in the data determined by ELISA. Thus, a discrepancy exists in the
      analysis of IgG2 ratios between NMR and ELISA methods. CONCLUSION: There was a
      discrepancy in the IgG2 ratios of patients with RA between NMR and ELISA methods,
      and we attribute this to a conformational difference in IgG2 in patients with RA.

PMID- 9034984
TI  - Efficacy and safety of meloxicam in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of meloxicam, a new acidic enolic
      nonsteroidal anti-inflammatory drug, at doses of 7.5 and 15 mg once daily in
      patients with rheumatoid arthritis (RA). METHODS: Meloxicam 15 and 7.5 mg daily
      was administered for 21 days in this double blind, randomized, placebo controlled
      study. 159 patients received meloxicam 7.5 mg, 162 received meloxicam 15 mg, and
      147 received placebo. RESULTS: Meloxicam 15 mg once daily was significantly
      superior (p < 0.05) to placebo in 3 of the 4 primary endpoints (disease activity
      assessed by the investigator, disease activity assessed by the patient, and
      reduction of the number of tender/painful joints). No difference was observed
      regarding number of swollen joints. The difference between meloxicam 7.5 mg once
      daily and placebo reached statistical significance in 2 of the 4 primary
      endpoints, disease activity assessed by the patient and number of tender/painful
      joints. A statistically significant difference between meloxicam 1.5 mg and 7.5
      mg was not observed for any primary endpoint. The rating of global tolerance by
      investigators and patients at the end of the study was similar in the 3 treatment
      groups, indicating that meloxicam and placebo were generally similarly well
      tolerated. However, there was a slightly higher incidence of gastrointestinal
      (GI) disturbances reported by patients receiving meloxicam 15 mg. GI adverse
      events were reported by 11, 11, and 16% of patients in the placebo, meloxicam 7.5
      mg, and meloxicam 15 mg groups, respectively. None were serious. CONCLUSION:
      Meloxicam in daily doses of 7.5 and 15 mg is effective in treating the signs and
      symptoms of RA.

PMID- 9034985
TI  - Variability of anticardiolipin antibody isotype distribution in 3 geographic
      populations of patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the prevalence of anticardiolipin antibodies (aCL) and
      isotype distribution and their clinical associations with the features of the
      antiphospholipid syndrome (APS) in 3 different ethnic groups of patients with
      systemic lupus erythematosus (SLE). METHODS: The study population consisted of
      152 African-American, 136 Afro-Caribbean (Jamaican), and 163 Hispanic (Colombian)
      unselected patients with SLE. Serum samples were studied for the prevalence of
      aCL and isotype distribution. All aCL measurements were performed in the same
      laboratory by ELISA. RESULTS: Positive results for 1 of the 3 aCL isotypes were
      found in 42 African-Americans (28%), 28 Afro-Caribbeans (21%), and 43 Hispanics
      (26%). IgG aCL was the dominant isotype in Hispanic and African-American
      patients, while IgA was the dominant isotype in Afro-Caribbeans. Of note, IgA aCL
      was found in all Afro-Caribbean patients who were aCL positive, while only 3
      patients in this group had IgG aCL and 2 had IgM aCL. Clinical features of the
      APS were found to correlate better in Hispanics than in African-Americans and
      Afro-Caribbean patients with aCL isotypes. CONCLUSION: Our data suggest the
      existence of ethnic differences in the prevalence and isotype distribution of aCL
      as well as in their clinical relevance in patients with SLE. Further studies of
      the role of genetic and/or environmental factors in the observed differences are
      required.

PMID- 9034986
TI  - Revisiting autoantibody profiles in systemic lupus erythematosus.
AB  - OBJECTIVE: To obtain more definitive assays of the spectrum of soluble
      autoantigens targeted by individual patients with systemic lupus erythematosus
      (SLE) and to determine whether the autoimmune response is restricted in
      specificity. Although there are many reports of a broad spectrum of autoantibody
      specificities in SLE, none has considered the diversity of autoantibody sets,
      which may more accurately describe the autoimmune response. METHODS: Sera of 68
      patients with SLE were assayed for autoantibodies by ELISA and/or
      immunoprecipitation. Specificities were grouped into sets, including double
      stranded (ds) DNA and/or histone, U1 RNP and/or Sm, Ro and/or La, ribosomes, Ku,
      Ki, and others. An analysis was also performed of reported SLE autoantibody
      profiles. RESULTS: The prevalences of autoantibody sets included: dsDNA and/or
      histone, 59%; U1 RNP and/or Sm, 40%; Ro and/or La, 41%; ribosomes, 4.4%; Ku,
      4.4%; Ki, 2.9%. On average, autoantibody positive patients had 2-3 autoantibodies
      (median = 2) and about 2-3 autoantibody sets (median = 2), consistent with a
      retrospective analysis of past studies. CONCLUSION: Immune dysregulation in SLE
      generally involves a multiplicity of autoantibody specificities. These data
      further support a model in which global immune dysregulation in SLE leads to
      organ-nonspecific autoimmunity against particular ubiquitous autoantigens.

PMID- 9034987
TI  - Circulating levels of tumor necrosis factor soluble receptors in systemic lupus
      erythematosus are significantly higher than in other rheumatic diseases and
      correlate with disease activity.
AB  - OBJECTIVE: To investigate the difference in acute phase protein responses between
      patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and
      spondyloarthropathies (SpA). METHODS: Circulating levels of cytokines inducing
      the production of acute phase proteins such as interleukin (IL)-6, IL-1 beta, and
      tumor necrosis factor (TNF)-alpha, and of cytokine inhibitors such as TNF soluble
      receptors (TNF-sR55 and TNF-sR75) and IL-1 receptor antagonist (IL-1ra), were
      measured in 2 cohorts of patients. The first cohort included 52 patients with SLE
      and 22 with RA, and the second included 21 with SLE, 20 with RA, and 18 with SpA.
      An examination at the time of blood collection and the Systemic Lupus Activity
      Measure (SLAM) index were used to assess disease activity in patients with SLE.
      Serum levels of IL-6 were measured using a biological assay, and concentrations
      of IL-1 beta, TNF-alpha, TNF-sR55, TNF-sR75, and IL-1ra were assessed by
      immunoassays. RESULTS: Although C-reactive protein (CRP) levels were
      significantly lower in SLE than in RA or SpA, the concentrations of circulating
      IL-6 or TNF-alpha were higher in SLE. The most striking observation was that TNF
      sR levels were significantly higher in SLE than in RA or SpA. The TNF-alpha: TNF
      sR ratio was also significantly lower in SLE than in RA. TNF-sR55 and TNF-sR75
      levels correlated with disease activity in SLE. CONCLUSION: The weak acute phase
      protein response in SLE may be explained by a decreased ratio between inducing
      cytokines and their inhibitors. In addition, TNF-sR may prove a useful biological
      marker for the followup of SLE, where acute phase protein response is generally
      low during disease exacerbations.

PMID- 9034988
TI  - Association of the Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology Damage Index with measures of disease activity and health
      status in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To examine the internal consistency and validity of the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage Index
      (SDI) with respect to disease activity, health status, and medication score.
      METHODS: A prospective cross sectional study of patients with systemic lupus
      erythematosus (SLE) attending a specialist lupus outpatient clinic between July
      1994 and February 1995. The internal consistency of the SDI components was
      examined using Cronbach's coefficient alpha. The associations of the SDI
      components with disease activity measured by the British Isles Lupus Assessment
      Group (BILAG) index, health status measured by the Medical Outcomes Study (MOS)
      Short Form 20, and with a medication score were analyzed using Spearman's rank
      correlation coefficient (p). RESULTS: 133 women and 8 men ranging in age from
      20.1 to 88.7 years (mean 41.1, SD 12.5) were studied. With few exceptions, the
      components of the SDI that reflect damage in different organ systems were not
      associated with each other. We found a significant although weak relationship
      between some related SDI and BILAG components (p 0.25 to 0.28; p < 0.01). While
      damage to the musculoskeletal system was associated with limitations in physical
      functioning measured with the MOS Short Form 20 (p-0.30; p < 0.01) and renal
      damage inversely with fatigue (p-0.23; p < 0.01) there was no significant
      relationship of other SDI components with the MOS Short Form 20. Renal and
      neuropsychiatric damage were associated significantly with the medication score
      (p 0.27 and 0.23; p < 0.01). CONCLUSION: The components of the SDI are valid in
      that they are associated with disease activity in the respective organ systems
      and some of them with a medication score. However, damage in different organ
      systems in SLE does not follow a common pattern. It is thus suggested that the
      SDI profile be used in addition to the SDI total score as an endpoint in clinical
      and epidemiological studies.

PMID- 9034989
TI  - Reduction in circulating dsDNA antibody titer after administration of LJP 394.
AB  - OBJECTIVE: To examine the safety and immunological effects, in patients with
      systemic lupus erythematosus (SLE), of LJP 394, a novel B cell toleragen designed
      to lower dsDNA antibodies. METHODS: Four women with stable SLE were given a 100
      mg infusion of LJP 394 and were followed for 4 weeks. Routine safety variables
      were measured, as well as anti-dsDNA, circulating immune complexes, complement,
      and complement split products. RESULTS: Anti-dsDNA titers were promptly lowered.
      At 4 weeks postinfusion, 2 patients' titers remained below baseline and 2
      returned to pretreatment levels. Transient increases in some complement split
      products were noted; however, no adverse clinical events occurred during or
      immediately after infusion. CONCLUSION: LJP 394 successfully and safely lowered
      anti-dsDNA in 4 patients with SLE. Immune complex formation and rapid elimination
      is the most likely explanation for the observed findings.

PMID- 9034990
TI  - Antiphospholipid antibodies among anti-U1-70 kDa autoantibody positive patients
      with mixed connective tissue disease.
AB  - OBJECTIVE: The association between antiphospholipid antibodies (aPL) and
      recurrent venous and/or arterial thrombotic events, fetal loss, and
      thrombocytopenia in systemic lupus erythematosus (SLE) has been well documented.
      Such an association has not been carefully assessed in mixed connective tissue
      disease (MCTD). Our aim was to assess the prevalence and clinical significance of
      aPL in anti-U1-70 kDa autoantibody positive patients with MCTD. METHODS: We
      compared 48 consecutive anti-U1-70 kDa autoantibody positive patients with MCTD
      versus 59 consecutive anti-U1-70 kDa autoantibody negative patients with SLE to
      determine the frequency of aPL and clinical features of the aPL syndrome.
      RESULTS: Among the patients with MCTD 7/48 (15%) had anticardiolipin antibodies
      (aCL) versus 24/59 (41%) patients with SLE (p < 0.005) and versus 2/150 (1%)
      apparently healthy blood donors (p < 0.001). Among patients with MCTD with aPL, 2
      were IgG, 3 IgM, and 2 both IgG and IgM isotypes; among patients with SLE 5 were
      IgG, 11 IgM, and 8 both IgG and IgM isotypes. No clotting events or other
      features of the aPL syndrome were found among the patients with MCTD compared
      with 26 events documented among the group of aCL positive patients with SLE (p <
      0.001). There were 10 patients with SLE with deep vein thrombosis, one with a
      pulmonary embolism, 2 with recurrent fetal loss, one with chorea, 2 with livedo
      reticularis, one with severe thrombocytopenia, and one with avascular necrosis.
      CONCLUSION: aCL were increased in patients with MCTD compared to controls.
      Furthermore, aCL were increased in SLE compared with both patients with MCTD and
      controls. Finally, while clotting events and other manifestations of the aPL
      syndrome occurred among the group of aCL positive patients with SLE these were
      distinctly absent from the aCL positive MCTD group.

PMID- 9034991
TI  - Vasculitis in familial Mediterranean fever.
AB  - OBJECTIVE: To evaluate the frequency of vasculitis, mainly in the forms of Henoch
      Schonlein purpura and polyarteritis nodosa (PAN), and to investigate the presence
      of occult blood in the first stool specimens after an abdominal attack in Turkish
      patients with familial Mediterranean fever (FMF). METHODS: Review of the charts
      of 207 patients with FMF seen between 1983 and 1993 with respect to clinical
      vasculitis. A prospective study designed to test the presence of occult blood in
      the first stool specimens obtained after abdominal attack and at least one week
      later in 36 patients with FMF compared with healthy and diseased controls.
      RESULTS: There were 15 patients with Henoch-Schonlein purpura (7%), 2 with
      definite and one with probable PAN (1%), one of whom developed perirenal
      hematoma. The diagnosis of FMF was made after the onset of Henoch-Schonlein
      purpura in 9 and subsequent to the development of PAN in one patient. Occult
      blood was positive in the first stool specimens obtained after an attack in 17 of
      the 36 patients with FMF (47%), a finding not reported previously. CONCLUSION:
      Vasculitis seems to be an important but not a widely recognized feature of FMF.

PMID- 9034992
TI  - Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with
      systemic sclerosis.
AB  - OBJECTIVE: To determine whether serum interleukin 4 (IL-4), IL-10, and IL-13
      levels in patients with systemic sclerosis (SSc) are elevated and whether they
      correlate with the clinical or serologic features of this disease. METHODS: Serum
      samples from patients with limited cutaneous SSc (ISSc) (n = 45), diffuse
      cutaneous SSc (dSSc) (n = 28), and control subjects (n = 30) were examined by
      ELISA. RESULTS: Serum IL-4 and IL-13 levels were significantly higher in patients
      with ISSc and dSSc than in the controls. Serum IL-10 levels were significantly
      higher in the patients with dSSc compared with controls. Elevated IL-10 levels
      were detected frequently in patients with arthralgia. Serum IL-13 levels
      correlated with erythrocyte sedimentation rates and C-reactive protein levels in
      patients. CONCLUSION: We suggest that IL-4, IL-10, and IL-13 may be some of the
      cytokines that contribute to the disease process, and that IL-13 may be a
      serologic indicator of systemic inflammation in patients with SSc.

PMID- 9034993
TI  - The clinical spectrum of remitting seronegative symmetrical synovitis with
      pitting edema. The Catalan Group for the Study of RS3PE.
AB  - OBJECTIVE: To describe the clinical and laboratory features and outcome of
      patients with remitting seronegative symmetrical synovitis with pitting edema
      (RS3PE). METHODS: A retrospective multicenter study of patients with RS3PE
      fulfilling the following criteria: (1) bilateral pitting edema of both hands, (2)
      sudden onset of polyarthritis, (3) age > 50 years, (4) seronegative for
      rheumatoid factor (RF). RESULTS: 27 patients with RS3PE were included, mean age
      71.7 years (58-92), 18 men (66.6%) and 9 women (33.3%). Relevant history was
      noted in 2 patients with polymyalgia rheumatica. Main clinical features were
      polyarthritis and edema of both hands. Polyarthritis involved metacarpophalangeal
      joints in 22 patients (81.5%), proximal interphalangeal joints in 19 (70.4%),
      wrists in 15 (55.5%), shoulders in 13 (48%), elbows in 3 (11.1%), knees in 9
      (33.3%), and ankles in 7 (25.9%). All patients were RF negative. Antinuclear
      antibodies were positive at low titer in 8 patients. Erosions were present in one
      patient. Two patients developed T lymphoma and one myelodysplastic syndrome.
      CONCLUSION: RS3PE is a heterogeneous syndrome the clinical history, presence of
      erosions, and evolution to hematological diseases in our patients suggest that
      RS3PE may not be a distinct clinical entity.

PMID- 9034994
TI  - Acute rheumatic fever in adults: a resurgence in the Hasidic Jewish community.
AB  - OBJECTIVE: To describe a series of adults diagnosed with acute rheumatic fever
      (ARF). METHODS: Retrospective chart review of 14 patients age > 18 years with
      suspected ARF between 1990 and 1994 in a private rheumatology practice setting.
      Four additional patients treated at our medical center were included in the
      study. RESULTS: Twelve patients met Jones criteria for rheumatic fever and were
      included in the study. Of these, only 3 had a childhood history of rheumatic
      fever. All had recent onset of arthritis and a history of antecedent sore throat.
      Only 4 patients, however, had throat cultures positive for B-hemolytic
      streptococcus. Nine patients were Hasidic Jews. Four patients had carditis. One
      patient had erythema marginatum, while chorea and subcutaneous nodules were not
      seen. Nine patients improved taking nonsteroidal antiinflammatory drugs or
      acetylsalicylic acid; 3 required steroid treatment to control severe arthritis.
      CONCLUSION: Our clinical experience suggests that ARF occurs frequently,
      especially among Hasidic Jewish adults. Due to the disabling nature of the
      arthritis and the significant incidence (33%) of carditis, strict adherence to
      penicillin prophylaxis guidelines is indicated.

PMID- 9034995
TI  - The involvement of phosphatidylinositol 3-kinase in crystal induced human
      neutrophil activation.
AB  - OBJECTIVE: We investigated whether phosphatidylinositol (PI) 3-kinase is involved
      in the signal transduction pathway leading to neutrophil activation by
      inflammatory microcrystals. METHODS: Neutrophil chemiluminescence and
      degranulation responses to opsonized crystals were measured in the presence of
      selective inhibitors known to inhibit PI 3-kinase activity in neutrophils.
      RESULTS: Wortmannin and LY 294002, 2 selective inhibitors of PI 3-kinase, were
      shown to inhibit neutrophil activation induced by plasma opsonized crystals of
      calcium pyrophosphate dihydrate (CPPD) [both monoclinic (M) and triclinic (T)
      forms] and monosodium urate monohydrate (MSUM). IC50 for wortmannin or LY 294002
      inhibition of crystal induced respiratory burst (measured by chemiluminescence)
      was about 3 nM and 0.3 microM, respectively, proving the pivotal role of PI 3
      kinase in neutrophil respiratory burst activation by all 3 crystals.
      Degranulation responses of neutrophils to CPPD(M) and CPPD(T) crystals were also
      inhibited by about 50% by wortmannin in the 10 to 20 nM concentration range,
      supporting the direct involvement of PI 3-kinase in signal transduction pathways
      leading to crystal induced neutrophil degranulation. All 3 crystals induced the
      activation of PI 3-kinase in neutrophils as measured by the increased PI 3-kinase
      activity associated with immunoprecipitated tyrosine phosphorylated proteins from
      1 min crystal-neutrophil incubations. Neutrophils pretreated with wortmannin at
      10 nM showed sub-basal levels of PI 3-kinase activity at all time points
      measured. CONCLUSION: PI 3-kinase plays a central role in the signal transduction
      pathways leading to respiratory burst and degranulation responses in neutrophils
      activated by inflammatory microcrystals.

PMID- 9034996
TI  - A systematic review of randomized controlled trials of pharmacological therapy in
      osteoarthritis of the hip.
AB  - OBJECTIVE: To systematically review all randomized controlled trials (RCT) of
      pharmacological therapy in osteoarthritis (OA) of the hip. To determine which
      nonsteroidal antiinflammatory drug (NSAID) is the most effective, and which NSAID
      is the most toxic. METHODS: A MEDLINE search was used to identify RCT of
      pharmacological therapy in patients with OA of the hip published between 1966 and
      August 1994. Qualitative assessments were performed using a quality scoring
      system designed for NSAID trials in rheumatoid arthritis. Both the design and
      analysis aspects of the trials were evaluated, each aspect rated on a scale of 0
      to 8. A quantitative method, which calculates the ratio of improvement produced
      by one NSAID to that produced by another, was used to rate the relative efficacy
      of different NSAID with respect to pain relief. Toxicity comparisons were made
      according to the authors' findings. RESULTS: 43 RCT were identified, and of
      these, 39 evaluated NSAID while 4 evaluated only analgesics. The median design
      and analysis scores were 2 and 4, respectively, 6 NSAID were included in at least
      5 trials; of these, indomethacin was rated more effective in 5 of its 7
      comparisons, but more toxic in 7 of 12 comparisons. Only 5 of the 29 (17%) NSAID
      comparisons found statistically significant differences in efficacy. CONCLUSION:
      NSAID trials in patients with OA of the hip appear to be weakened by the lack of
      standardization of case definition of OA, and also by the lack of standardization
      of outcome assessments. No recommendations for the choice of specific NSAID
      therapy in hip OA can be offered based on this analysis.

PMID- 9034997
TI  - Degenerated human articular cartilage at autopsy represents preclinical
      osteoarthritic cartilage: comparison with clinically defined osteoarthritic
      cartilage.
AB  - OBJECTIVE: To investigate whether macroscopically fibrillated human articular
      knee cartilage observed at autopsy can be considered an early, preclinical phase
      of osteoarthritis (OA). METHODS: Histological and biochemical characteristics of
      3 types of articular knee cartilage were compared: macroscopically degenerated
      knee cartilage obtained at autopsy (6 donors) from donors without clinical
      history of OA, normal healthy knee cartilage obtained at autopsy (6 donors), and
      OA cartilage obtained during joint replacement surgery from patients (n = 6) with
      clinically defined OA of the knee. From the same donors synovial tissue and
      synovial fluid were obtained and analyzed for features of inflammation. RESULTS:
      Histological changes of OA were comparable for degenerated and OA cartilage and
      significantly different from normal cartilage. Content and synthesis of
      proteoglycans showed intermediate levels for degenerated tissue compared to
      normal and OA cartilage. Analysis of synovial tissue revealed a low, mild, and
      moderate degree of inflammation for joints with normal, degenerated, and OA
      cartilage, respectively. The same sequence was found for metalloproteinase
      activity in synovial fluid. CONCLUSION: In general, all changes observed in OA
      joints were, to a lesser extent, observed in the joints with degenerated
      cartilage and were significantly different from joints with normal cartilage. We
      conclude that cartilage degeneration observed at autopsy can be considered a
      preclinical phase of OA, suitable for studying the process of cartilage
      degeneration in OA.

PMID- 9034998
TI  - Synovial membrane inflammation and cytokine production in patients with early
      osteoarthritis.
AB  - OBJECTIVE: To establish the presence of inflammation in and cytokine production
      by synovial membranes from patients with various stages of early osteoarthritis
      (OA), with knee pain, normal knee radiographs, and arthroscopic evidence of
      chondral damage. METHODS: Synovial membrane samples were obtained from the knees
      of 63 patients at the time of arthroscopy for unexplained knee pain or at the
      time of joint replacement surgery. Evaluations of synovial membrane variables
      including thickness of lining layer, vascularity, and inflammatory cell
      infiltrate were by a blinded observer. In a subset of 20 patients, production of
      interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), tumor necrosis
      factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and
      protein levels was determined using in situ hybridization with biotin labeled
      ribo-probes and immunohistochemistry. RESULTS: There was evidence of thickening
      of the lining layer, increased vascularity, and inflammatory cell infiltration in
      synovial membranes from patients with all grades of OA, with the most marked
      changes seen in synovial tissue from patients with advanced grades of OA.
      Similarly, production of IL-1 alpha, IL-1 beta, and TNF-alpha was present in
      synovial membranes from all patients with OA, irrespective of the degree of
      articular cartilage damage. There was a trend to decreased levels of IL-1ra in
      synovial membranes from patients with OA that did not attain statistical
      significance. Similarly, there was a decrease in the ratio of IL-1ra to IL-1
      alpha and beta with increasing grades of OA. CONCLUSION: Chronic inflammatory
      changes with production of proinflammatory cytokines are a feature of synovial
      membranes from patients with early OA, with the most severe changes seen in
      patients at the time of joint replacement surgery resembling those seen in
      rheumatoid arthritis. This low grade synovitis results in the production of
      cytokines that may contribute to the pathogenesis of OA.

PMID- 9034999
TI  - Markers of inflammation and immune activation in chronic fatigue and chronic
      fatigue syndrome.
AB  - OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from
      immune activation. We examined the role of serum markers of inflammation and
      immune activation among patients with CFS and in those with chronic fatigue (CF)
      not meeting the case definition. METHODS: Assays for soluble interleukin 2 (IL-2)
      receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were
      performed in 153 fatigued patients in a referral clinic. Patients were classified
      according to whether they met criteria for CFS, reported onset of illness with a
      viral syndrome or had a temperature > 37.5 degrees C on examination. RESULTS:
      Compared to control subjects, mean concentrations of C-reactive protein, beta 2
      microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and
      CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated
      among febrile patients compared to those without this finding (p < or = 0.001),
      but other consistent differences between patient subgroups were not observed. The
      presence of several markers was highly correlated (p < 0.01). CONCLUSION: Our
      findings that levels of several markers were significantly correlated points to a
      subset of patients with immune system activation. Whether this phenomenon
      reflects an intercurrent, transient, common condition, such as an upper
      respiratory infection, or is the result of an ongoing illness associated process
      is unknown. Overall, serum markers of inflammation and immune activation are of
      limited diagnostic usefulness in the evaluation of patients with CSF and CF.

PMID- 9035000
TI  - A standardized manual tender point survey. I. Development and determination of a
      threshold point for the identification of positive tender points in fibromyalgia
      syndrome.
AB  - OBJECTIVE: To (a) develop a standardized tender point examination protocol
      [Manual Tender Point Survey (MTPS)] as a diagnostic procedure to evaluate the
      tender point (TP) criterion for fibromyalgia syndrome (FM) and (b) determine a
      threshold point for positive TP. METHODS: A standardized MTPS consisted of
      standardized components including (a) location of the survey sites, (b) patient
      and examiner positioning, (c) order of examination, (d) pressure application
      technique, and (e) pain severity rating scores [0 (no pain) - 10 (worst pain)].
      Seventy patients with FM and 70 with chronic headache were examined using the
      MTPS protocol. RESULTS: A pain severity score of 2 (i.e., 0-1 = negative) was
      found to be an optimal threshold point for identifying positive TP, with
      sensitivity of 88.57% and specificity of 71.43%. These results are comparable to
      the sensitivity and specificity of the 1990 multicenter study. CONCLUSION: The
      MTPS provides a step-by-step, standardized TP examination protocol, which is
      sensitive and specific in discriminating patients with FM from patients with
      chronic headache.

PMID- 9035001
TI  - Idiopathic limb edema in children with chronic arthritis: a multicenter report of
      12 cases.
AB  - Lymphedema, a well known extraarticular manifestation of rheumatoid arthritis,
      has been rarely described in children with idiopathic chronic arthritis. We
      describe 12 cases of lymphedema and idiopathic arthritis of childhood seen at 4
      different pediatric rheumatology centers. Eight patients were girls, 4 boys; the
      age at appearance of lymphedema ranged from 2.3 to 17 years. In all patients
      except one, lymphedema was localized to the lower limbs. The outcome of
      lymphedema was variable, but not always related to the arthritis course, and was
      mostly independent of any specific therapy. Lymphography was performed in only
      one patient, and revealed lack of lymphatic drainage in the affected leg. We
      conclude that the association of lymphedema and idiopathic arthritis of childhood
      is not rare; this association is unlikely to be coincidental, even though the
      pathogenetic mechanisms are currently not well understood.

PMID- 9035002
TI  - Catastrophic antiphospholipid antibody syndrome in pediatric systemic lupus
      erythematosus.
AB  - Catastrophic antiphospholipid antibody syndrome, reported in a minority of
      patients with circulating antiphospholipid antibodies, is characterized by
      widespread vascular occlusions. The term "catastrophic" has been used to describe
      the severity of symptomatology, sometimes leading to death. We describe a girl
      aged 11 years, fulfilling diagnostic criteria for systemic lupus erythematosus,
      with recurrent episodes of thromboembolic phenomena involving lung and skin,
      complicated with disseminated intravascular coagulation. Treatment with warfarin
      ultimately resulted in effective control of the disease.

PMID- 9035003
TI  - Juvenile systemic granulomatosis manifesting as premature aging syndrome and
      renal failure.
AB  - We describe a case of juvenile systemic granulomatosis in a 22-year-old woman.
      The rash consisted of purple papules and first appeared at the age of one year.
      She had persistent symmetrical painless boggy tenosynovitis with minimal
      roentgenographic changes and chronic granulomatous symptoms. Uveitis resulted in
      visual impairment. She also had granulomatous changes in her vessels. Renal
      impairment developed; however, neither renal artery stenosis nor hypercalcemia
      was found. Clinical features included the development of premature aging with
      alopecia, which differed from the previously reported progeria syndrome.
      Poikiloderma may cause a prematurely aged appearance. Our report expands the
      clinical spectrum of systemic granulomatosis to include the development of
      premature aging with alopecia.

PMID- 9035004
TI  - Pseudo-synovial cyst arising at the pubic bone region and forming a large femoral
      inguinal mass.
AB  - We describe a patient with rheumatoid arthritis who presented a large femoral
      inguinal mass. The mass proved to be a synovial cyst-like structure communicating
      with rigid cystic lesions at the pubic bone. No obvious communication between the
      cystic lesions and the hip joint or bursae was seen by hip arthrogram or in
      surgery. Pathological examination of the cystic lesion at the pubic bone revealed
      infiltration of multiple rheumatoid nodules with marked fibrinoid necrosis into
      the bone, with synovium-like tissue on it. However, no synovial tissue was
      observed in the femoral-inguinal mass. These findings suggest that the femoral
      inguinal mass was not a true synovial cyst but can be called a pseudo-synovial
      cyst arising at the pubic bone region.

PMID- 9035005
TI  - Coexistence of serum anti-DNA topoisomerase I and anti-Sm antibodies: report of 3
      cases.
AB  - We describe 3 Japanese patients having both serum anti-DNA topoisomerase I and
      anti-Sm antibodies. All 3 patients had typical features of systemic lupus
      erythematosus, such as glomerulonephritis, in addition to skin thickening and
      systemic sclerosis related organ involvement, including pulmonary interstitial
      fibrosis and renal crisis. This is the first report of the coexistence of these 2
      disease specific autoantibodies.

PMID- 9035006
TI  - The co-occurrence of acute rheumatic fever and AIDS.
AB  - We describe a patient with advanced acquired immunodeficiency syndrome (AIDS) who
      presented with evidence of carditis, arthritis, and chorea in the setting of
      fever, and serologic evidence for recent streptococcal infection. Several
      features atypical for rheumatic fever were present and included persistently high
      titer of antistreptolysin O, the simultaneous occurrence of chorea and arthritis,
      and the presence of chorea in a sexually mature adult man. The differential
      diagnosis of arthritis in a host at risk for human immunodeficiency virus should
      be expanded to include acute rheumatic fever, which may manifest atypical
      features.

PMID- 9035007
TI  - Prevention of corticosteroid induced osteoporosis.

PMID- 9035008
TI  - Simultaneous presentation of giant cell arteritis and chronic lymphocytic
      leukemia.

PMID- 9035009
TI  - Juvenile psoriatic arthritis: a new clinical entity?

PMID- 9035010
TI  - Biopsy of labial salivary glands and lacrimal glands in the diagnosis of
      Sjogren's syndrome.

PMID- 9035011
TI  - The thrombin-antithrombin complex in rheumatoid arthritis.

PMID- 9035012
TI  - Visual hallucinations induced by intraarticular injection of steroids.

PMID- 9035013
TI  - Rheumatic and musculoskeletal diseases and impaired quality of life: a challenge
      for rheumatologists.

PMID- 9035014
TI  - Low dose etodolac in rheumatoid arthritis: a review of early studies.
AB  - Short and longterm safety and efficacy of etodolac in a wide range of dosages in
      patients with rheumatoid arthritis (RA) are summarized. Data from 8 studies, one
      longterm (1 year) and 7 short term (< 10 weeks) were analyzed. All studies were
      double blind and randomized; 6 had a placebo control group and 7 had an active
      comparator (aspirin, piroxicam, or sulindac) group. In the 1 year study, doses of
      etodolac were titrated up from 50 mg bid until clinical efficacy was achieved and
      maintained; the highest dose for > 80% of patients was 150 mg bid. In 6 of the 7
      short term studies, dosages were fixed and ranged from 50 to 300 mg bid.
      Continuation rates and 4 efficacy measures (patients' and physicians' global
      assessments and numbers of painful and swollen joints) were assessed. The 1 year
      study enrolled 475 patients. Overall continuation rates for etodolac and aspirin
      were comparable, but more patients taking aspirin discontinued the study because
      of adverse events. Most patients given etodolac who discontinued treatment for
      lack of efficacy did so during the titration phase. Four of 236 patients received
      aspirin and none received etodolac developed ulcers. For patients continuing to
      take the study medication, improvement in efficacy variables in the etodolac
      group was comparable to that in the aspirin group. In the 7 short term studies,
      dose related improvement in patients' and physicians' global assessments and
      number of swollen joints was noted in the etodolac group compared with the
      placebo group; this improvement was statistically significant at dosages of > or
      = 200 mg bid. Pooled analysis showed the efficacy of etodolac at dosages of 300
      mg bid to be similar to that of comparator drugs. These short and longterm
      studies show that etodolac in a wide range of dosages, starting at 200 mg bid,
      has clinical efficacy in the treatment of RA. It is significantly better
      tolerated than aspirin, and at doses of 300 mg bid, it is as effective as
      sulindac, aspirin, and piroxicam.

PMID- 9035015
TI  - Comparison of the efficacy and safety of etodolac and piroxicam in patients with
      rheumatoid arthritis. Etodolac Study 326 Rheumatoid Arthritis Investigators
      Group.
AB  - The efficacy and safety of etodolac and piroxicam in patients with active
      rheumatoid arthritis were compared. A 12 week, double blind, parallel group study
      was conducted at 28 centers in patients 18 to 75 yrs old, randomized to receive
      etodolac or piroxicam. Primary efficacy criteria were investigators' and
      patients' global assessments and numbers of painful and swollen joints. Secondary
      criteria were duration of morning stiffness, grip strength, time to walk 50 feet.
      Westergren erythrocyte sedimentation rate (ESR), pain intensity, painful and
      swollen joint scores, and articular index. Of 426 patients enrolled, 140 received
      etodolac 200 mg bid (E200), 147 received etodolac 300 mg bid (E300), and 139
      received piroxicam 20 mg qd (P20). Efficacy analyses included data from 361
      patients. No significant differences occurred between the E300 and piroxicam
      groups in change from baseline for the primary efficacy variables. All treatments
      produced significant (p < 0.01) improvement from baseline in all efficacy
      variables, except that only E300 produced a significant decrease from baseline in
      ESR. No significant differences occurred in the incidence of any specific adverse
      event. Six patients given E200, 7 given E300, and 10 given piroxicam withdrew
      because of adverse reactions. The incidence of patients with hemoglobin and
      hematocrit results below the normal range was significantly higher for piroxicam
      than for either etodolac regimen. Three patients receiving piroxicam had
      gastrointestinal ulcers. Thus, E300 and P20 provided comparable efficacy. E200
      was less effective for some variables early in the study.

PMID- 9035016
TI  - Double blind evaluation of the long-term effects of etodolac versus ibuprofen in
      patients with rheumatoid arthritis.
AB  - We compared the longterm efficacy and safety of 2 dosages of etodolac with that
      of ibuprofen in the treatment of active rheumatoid arthritis (RA). The ability of
      etodolac to retard, arrest, reverse, or heal joint damage due to RA was also
      evaluated. Patients in the early stages of RA were assigned randomly to 3
      parallel groups for up to 3 years of therapy: etodolac at 150 mg bid, etodolac at
      500 mg bid, and ibuprofen 600 mg qid. Concurrent disease modifying antirheumatic
      drugs were not permitted; established low dosage corticosteroid therapy could be
      continued. A total of 1446 patients was enrolled. About 50% of patients completed
      one year; dropout rates were comparable between groups. Both etodolac dosages
      provided comparable efficacy to that of ibuprofen during the first 2 months;
      longterm assessment showed that 1000 mg/day of etodolac produced superior
      improvement as assessed by patients' opinions and number of swollen joints. About
      2% of patients in each group achieved remission, and radiographs showed no
      difference in disease progression between treatments. The incidences of adverse
      events were comparable, although dyspepsia and rash occurred less frequently with
      300 mg/day of etodolac than with 2400 mg/day ibuprofen. A higher incidence of
      gastrointestinal ulcers and bleeding was seen with ibuprofen. Changes in hepatic
      and renal function were of minor clinical significance and were similar between
      the 3 groups. Both dosages of etodolac were comparable to 2400 mg/day ibuprofen
      in treating RA. All 3 treatment regimens were well tolerated.

PMID- 9035017
TI  - Etodolac (Lodine) in the treatment of osteoarthritis: recent studies.
AB  - Etodolac (Lodine) has been marketed in the United States since 1991 for managing
      pain and for acute and longterm treatment of the signs and symptoms of
      osteoarthritis (OA). Etodolac was recently approved for the treatment of
      rheumatoid arthritis. We review the results of 3 recent 4 week, multicenter,
      placebo controlled, parallel group studies that compared the efficacy and safety
      of etodolac with naproxen and nabumetone. Because studies of etodolac in the
      treatment of OA concentrated on bid doses, the first study compared etodolac 800
      mg/day given as 400 mg bid (106 patients) and 200 mg qid (105 patients) with
      naproxen 1000 mg/day (109 patients) and placebo (104 patients). Etodolac was as
      effective as naproxen, and the 2 dosage schedules of etodolac were comparable.
      The 2nd study compared etodolac 400 mg bid (86 patients) with naproxen 500 bid
      (82 patients) and placebo (86 patients). Etodolac was again found to be as
      effective as naproxen. The 3rd study compared etodolac 400 mg bid (91 patients)
      with nabumetone 1500 mg/day (89 patients) and placebo (90 patients). The results
      indicated that the efficacy of etodolac was comparable to that of nabumetone and
      resulted in significantly better scores at endpoint on the investigator's overall
      assessment and patient's global assessment. In all 3 studies there were no
      significant differences among the groups in the frequency of study events or
      premature discontinuations as a result of study events. The most common adverse
      event was digestive system disturbance, which was mild to moderate in severity.
      The results of these studies confirm the efficacy and safety of etodolac in
      managing the signs and symptoms of OA.

PMID- 9035018
TI  - Regulation of prostaglandin synthesis by antiinflammatory drugs.
AB  - The prostaglandins (PG), thromboxanes, and leukotrienes (LT) are potent groups of
      mediators derived from arachidonic acid. The functions of these compounds are
      numerous and involve every organ system, but their roles in physiology and
      pathology are not completely understood. PG and LT are important mediators of
      inflammatory reactions. Convincing evidence supports the hypothesis than
      inhibition of PG synthesis accounts for both the major therapeutic
      antiinflammatory and toxic side effects of the nonsteroidal antiinflammatory
      drugs. New research has revealed that PG are synthesized by 2 forms of the enzyme
      cyclooxygenase, COX-1 and COX-2. Since COX-1 generally produces PG responsible
      for cytoprotective functions and COX-2 produces PG in inflammatory reactions, it
      is a reasonable hypothesis that drugs that are selective inhibitors of COX-2
      should be effective antiinflammatory agents with few toxic side effects.

PMID- 9035019
TI  - Tissue selective inhibition of prostaglandin biosynthesis by etodolac.
AB  - Inflammation is a complex process involving numerous mediators. Because
      prostaglandins (PG) have been implicated as mediators in all stages of
      inflammation, inhibition of their synthesis provides the basis for the
      therapeutic effects of nonsteroidal antiinflammatory drugs (NSAID). Treatment
      with NSAID is usually accompanied by gastric side effects, attributed to
      interference with the formation of cytoprotective PG in gastric mucosa. An ideal
      NSAID should inhibit PG synthesis at the site(s) of inflammation but not in
      gastric mucosa. Experimental and clinical data support the view that this
      criterion has been met by etodolac, a structurally distinct NSAID. Thus, in rats
      and humans with rheumatoid arthritis, longterm daily administration of etodolac
      at effective antiinflammatory dosages (3 mg/kg in rats; 600 mg in humans) had no
      effect on PGF2 and prostacyclin levels in gastric mucosa. In contrast,
      significant decreases in gastric PG levels occurred with antiinflammatory doses
      of aspirin, naproxen, and piroxicam. Cyclooxygenase (COX), the pivotal enzyme in
      PG biosynthesis, exists in 2 isoforms: constitutive COX-1, which produces the PG
      required for maintenance of normal cell activity (e.g., gastric cytoprotection),
      and COX-2, which is induced in restricted tissue-specific fashion (e.g., by
      inflammatory stimuli). The antiinflammatory action of NSAID may result from
      inhibition of COX-2, whereas their gastric side effects may result in large part
      from inhibition of COX-1; thus, a preferred NSAID should inhibit COX-2 but not
      COX-1. Results show that etodolac has 10-fold selectivity for COX-2 and indicate
      that etodolac's pharmacotherapeutic efficacy can be explained by its demonstrably
      selective inhibition of COX-2, amplified by its favorable tissular
      pharmacokinetics. The sparing of COX-1 activity in gastric mucosa gives rise to
      etodolac's noted gastric tolerance.

PMID- 9035020
TI  - An introduction to using computer simulation in healthcare: patient wait case
      study.
AB  - As healthcare continues to become more competitive, the ability to assess
      tradeoffs between resource utilization, service, and operating costs grows in
      importance, such as with respect to appointment access, waiting room delays, and
      telephone service. This paper discusses the use of simulation analysis for
      studying and improving these and other health systems. A case study concerning
      pediatric waiting times illustrates typical steps involved in a simulation study,
      possible types of analyses, and resources required. Other healthcare uses of
      stimulation, pitfalls to avoid, and software selection also are discussed
      briefly.

PMID- 9035021
TI  - Surgical process scheduling: a structured review.
AB  - There is no generally accepted definition of surgical process scheduling
      available in the literature; nursing researchers, physicians, administrators, and
      management scientists each view scheduling differently. To overcome this
      communication problem, a number of authors have proposed conceptual frameworks
      for surgical process scheduling. These frameworks have unfortunately been either
      unsatisfactory or incomplete. In this paper, we describe a conceptual framework
      for surgical process scheduling and use it to classify the existing literature.
      Results from the review indicate that while operational aspects of advance and
      allocation scheduling are well understood, further research should be directed
      towards resolving scheduling issues at strategic and administrative levels. In
      addition, techniques for integrating operating room (OR) scheduling with other
      hospital operations are required.

PMID- 9035022
TI  - Uncertainty considerations in group decisions: staffing and ratesetting in a
      health promotion center.
AB  - There are a variety of methods for including risk or uncertainty in Group
      Decision Support Systems (GDSS). Monte Carlo simulation is one method. An
      application of Monte Carlo simulation in Group Decisions and GDSS for
      diversification of services is presented in this paper. Specifically, the
      uncertainty associated with the finances of a Health Promotion Center are
      evaluated for staffing and rate setting. The distributions of outcome variables
      are used in decision rules.

PMID- 9035023
TI  - Using simulation to improve the operational efficiency of a multi-disciplinary
      clinic.
AB  - A recent trend in health care is to provide patients with the benefits of multi
      disciplinary care during a single clinic visit. The University of Michigan Breast
      Care Center is a leading example of a multi-disciplinary clinic which has served
      the Midwest United States since 1985. A hallmark of the Breast Care Center
      operation is a patient care conference immediately following the clinical
      evaluation sessions, where each case is discussed by a group of experts for
      immediate evaluation and generation of recommendations. The Center has
      experienced significant increases in the number of patient visits over the nine
      years since its inception. The patient mix, initially all new patients, has
      matured, and returning patients are now a significant portion of the clinic load.
      Unfortunately, the success of the Breast Care Center strained its smooth
      operation. Physicians were unable to attend the patient care conference because
      the clinical evaluation sessions were too busy, and this undermined the quality
      of the care recommendations generated. Patients were complaining about long waits
      in the Breast Care Center and delays in getting their next appointment. To
      examine these operational problems and to suggest corrective actions, a
      simulation study was conducted. This paper reports the results of this study. Our
      findings provide interesting insights into the operation and management of multi
      disciplinary clinics.

PMID- 9035024
TI  - An emergency department simulation and a neural network metamodel.
AB  - This paper describes a discrete event stochastic simulation of a hospital
      emergency department, and the development of a metamodel of that simulation. The
      metamodeling technique used is artificial neural networks, which are trained
      utilizing the output of the simulation. The performance of the neural network
      metamodel is compared to the simulation performance for estimating the mean and
      variance of patient time in the emergency department.

PMID- 9035025
TI  - Using simulation to reduce length of stay in emergency departments.
AB  - A growing number of hospitals are using health care-specific simulation
      technology to help identify process improvements, particularly when there are a
      number of alternatives under consideration. New software is now available which
      specifically meets the unique needs of health care. This paper describes how a
      team at one Emergency Services department in a SunHealth alliance hospital used
      simulation technology to test alternatives and choose a solution to significantly
      reduce the length of stay for patients in the Emergency Department.

PMID- 9035034
TI  - The role of the aryl hydrocarbon receptor in animal development, physiological
      homeostasis and toxicity of TCDD.

PMID- 9035035
TI  - Phenobarbital induction of cytochrome P450 genes in primary hepatocyte and
      transgenic models.

PMID- 9035037
TI  - Role of cross talk between superoxide and NO in the energy metabolism and
      pathogenesis of vasogenic tissue injury.

PMID- 9035036
TI  - Thioredoxin/adult T-cell leukemia-derived factor (ADF) and redox regulation.

PMID- 9035038
TI  - Activation of the phagocyte NADPH oxidase.

PMID- 9035039
TI  - In vivo ESR measurements of free radical reactions in living mice.

PMID- 9035040
TI  - Strategic proposals for predicting drug-drug interactions during new drug
      development: based on sixteen deaths caused by interactions of the new antiviral
      sorivudine with 5-fluorouracil prodrugs.

PMID- 9035041
TI  - Strategic proposals to avoid drug interactions during drug development: a lesson
      from a terfenadine-related drug interaction.

PMID- 9035042
TI  - Strategic proposals to avoid toxic drug interactions during new drug development:
      molecular toxicology proposals.

PMID- 9035043
TI  - Strategic proposals for avoiding toxic interactions with drugs for clinical use
      during development and after marketing of a new drug: pharmacokinetic
      consideration.

PMID- 9035044
TI  - A proposal for avoiding toxic interactions of a drug under development to
      estimate inhibitory ability on the drug metabolizing enzymes in human liver.
AB  - Drug interactions can be divided into those involving the pharmacokinetics of a
      drug and those affecting the pharmacodynamic response to it. Following strategies
      should be considered for avoiding pharmacokinetic drug interactions of new
      chemical entities under development. 1. To estimate the major metabolic pathways
      (including metabolic activation) using human liver preparations. 2. To identify
      the enzyme systems participating in the major metabolic pathways. 3. To examine
      metabolic inhibition for other drugs and by other drugs. 4. To confirm a
      pharmacokinetic effect for the combined drugs in vivo.

PMID- 9035045
TI  - Strategic proposals for avoiding toxic interactions with drugs for clinical use
      during development and after marketing of a new drug--proposals for designing non
      clinical and clinical studies--is the non-clinical study useful?
AB  - Since sorivudine incident has happened in Japan in 1993, an adverse drug-drug
      interaction has been of special meanings at each step of new drug development
      including the discovery step, NDA process, and on market. While it is known that
      several mechanisms are involved in the drug-drug interactions, the mechanisms
      related to drug metabolism are 1) inhibition of drug metabolizing enzymes, 2)
      induction of the enzymes, 3) drug absorption, 4) renal excretion, 5) hepatic
      transport, and 6) protein binding (displacement) interaction. In this report,
      proposals to avoid serious/lethal drug-drug interactions are presented with the
      examples. The proposals are: 1) To estimate the drug-drug interactions in
      consideration of the mechanisms reported so far, 2) To be especially careful for
      drugs with a small therapeutic index and severe/lethal toxicity, 3) To estimate
      the drug-drug interactions in consideration of physiological factors of patients,
      who receive drugs in combination, 4) Not to leave the mechanism unclear, when
      some data, which do not deny the critical drug-drug interactions, were obtained,
      and 5) To conduct the drug-drug interaction studies in humans in careful
      consideration of the safety.

PMID- 9035046
TI  - Basic strategy for avoiding drug interaction during stage of drug development;
      proposals relative to planning of non-clinical and clinical studies and how
      clinical trials should be planned.

PMID- 9035047
TI  - Single dose toxicity and repeated dose toxicity studies: introductory remarks.

PMID- 9035048
TI  - Current issues with regard to single dose toxicity studies.

PMID- 9035049
TI  - ICH Topic "6 vs 12 months" for long-term repeated dose studies in dogs.

PMID- 9035050
TI  - Case studies defining non-toxic and toxic dose of pharmaceuticals.

PMID- 9035052
TI  - Standard protocols based on the ICH guidelines for reproductive and developmental
      toxicity studies: an international implementation.

PMID- 9035051
TI  - Current status of implementation of the ICH guideline in Japan.

PMID- 9035053
TI  - Assessment of male reproductive toxicity in rats under ICH guidelines.

PMID- 9035054
TI  - How will the genotoxicity guidelines for pharmaceuticals be changed by the ICH
      agreement.

PMID- 9035055
TI  - A case study: evaluation of results and selection of additional studies.

PMID- 9035056
TI  - Genotoxicity tests. Considerations regarding the selection of a standard battery
      test.

PMID- 9035057
TI  - Testing for carcinogenicity of pharmaceuticals.

PMID- 9035058
TI  - Assessment of carcinogenicity using transgenic animals.

PMID- 9035059
TI  - Initiation-promotion model for assessment of carcinogenicity: medium-term liver
      bioassay in rats for rapid detection of carcinogenic agents.
AB  - To bridge the gap between long-term carcinogenicity tests and short-term
      screening assays, a medium-term liver bioassay system for rapid detection of
      carcinogenic agents using male F344 rats has been developed. The system is
      fundamentally based on the two-stage hypothesis of carcinogenesis: initiation
      with diethylnitrosamine (200 mg/kg, ip) is followed by test chemical
      administration during the second stage in combination with 2/3 partial
      hepatectomy. It requires only 8 weeks for the animal treatment and a further few
      weeks for quantitative analysis of immunohistochemically-demonstrated glutathione
      S-transferase placental form positive hepatic foci. A total of 277 chemicals have
      already been analyzed in this laboratory and the efficacy of the system for
      hepatocarcinogens has thereby been well established. This bioassay is
      particularly useful for dose-response and chemical mixture studies usually
      requiring large-scale experiments and also for evaluation of chemopreventive
      agents. Furthermore, medium-term multi-organ bioassay system, using 5 different
      chemical carcinogens (DEN, MNU, BBN, DMH and DHPN) has also been established for
      rapid detection of not only hepatocarcinogens, but also other carcinogens.

PMID- 9035060
TI  - Case study of carcinogenicity by initiation-promotion model.

PMID- 9035061
TI  - Study design and statistical analysis of toxicokinetics: a report of JPMA
      investigation of case studies.
AB  - In 1994, the Japanese Pharmaceutical Manufacturers Association (JPMA) conducted a
      questionnaire survey on case studies of toxicokinetics which were recently
      conducted its member companies. The present paper summarizes study designs and
      results of data analysis of 102 cases of repeated oral dose toxicity studies with
      dogs, monkeys, rats or mice. The statistical analysis of toxicokinetic data
      introduced in this paper, e.g. log-transformation of concentration data, analysis
      of variance and regression analysis, may be useful in clarifying the
      comprehensive effects of test doses, duration of repeated dosing, and sex of test
      animal on the systemic exposure. Suggestions are made on how experimental design
      can aid the efficient conduct of toxicokinetic studies in the face of limits on
      the number of animals.

PMID- 9035062
TI  - Points to be considered for conducting toxicokinetic studies under GLP and for
      validating analytical methods.
AB  - Issues discussed by TK Working Group of the JPMA for the implementation of ICH
      guideline for toxicokinetics (TK) are summarized. 1) A unique management system
      may be needed for toxicokinetic studies, when TK measurements are conducted in a
      center for pharmacokinetics and metabolism studies, i.e. in a separate location
      or by an independent organization from those for toxicity studies. 2) TK
      measurement should be conducted in compliance with the protocols and validated
      SOPs for analytical methods. 3) Every time when study conditions in toxicity
      studies and/or TK measurement are changed, the analytical method should be more
      or less revalidated. The present paper will discuss some practical issues to be
      involved in such situations, and possible countermeasures for them.

PMID- 9035063
TI  - Future prospects for toxicokinetics: its ability to predict drug adverse events
      in humans.

PMID- 9035064
TI  - Outline and discussion points of guidance for repeated dose tissue distribution
      studies.

PMID- 9035065
TI  - The possibility of predicting tissue accumulation after repeated dosing using a
      single-dose tissue distribution study.

PMID- 9035066
TI  - Safety assessment of biotechnology-derived pharmaceutical products. General
      principles and the relevant cases.

PMID- 9035067
TI  - Pharmacokinetics and toxicokinetics of bio-pharmaceuticals: technical problems.

PMID- 9035068
TI  - Trials to develop transgenic/immunodeficient mice.

PMID- 9035070
TI  - Mitogenic activity of Clostridium perfringens enterotoxin in human peripheral
      lymphocytes.
AB  - Clostridium perfringens enterotoxin (CPE) was found to possess interferon (IFN)
      producing and mitogenic activities to human peripheral blood mononuclear cells.
      Both activities were demonstrated only in the T lymphocyte-rich fraction from
      healthy volunteers. The IFN produced appeared to be gamma-type since the activity
      of the IFN was neutralized by antiserum against human IFN-gamma. With formalin
      treated CPE, the IFN-producing and mitogenic activities were weakly found.
      Similar findings were also obtained in the mouse lethality and cytotoxicity to
      Vero (African green monkey) cells, suggesting that the biological activities of
      the CPE molecule may be existing on the similar (or the same) sites. From these
      findings, human peripheral T cells may be one of useful reagents to study the
      mode of action of CPE since CPE was found to be a T cell mitogen which is
      supposed to be a superantigen.

PMID- 9035069
TI  - Characterization of some Theileria parva stocks from Zambia using monoclonal
      antibodies.
AB  - Theileria parva parasites have been isolated from different location in Zambia
      where malignant theileriosis has been recorded. A total of 16 bovine lymphocytic
      cell lines infected with T. parva schizonts were characterized using a panel of
      anti-schizont monoclonal antibodies (MAbs). Comparison of the Theileria stocks
      isolated before (old) and after (new) the Muguga cocktail of T. parva from Kenya
      was used to vaccinate cattle against theileriosis in Zambia revealed differences
      in their reactivity against MAbs. The new isolates are showing MAb profiles
      similar to that exhibited by the Muguga cocktail which was used to vaccinate
      cattle in these areas between 1983 and 1989. These results suggest that the use
      of the Muguga cocktail to vaccinate animals against theileriosis in Zambia may
      have introduced Theileria stocks of different antigenic properties.

PMID- 9035071
TI  - A characteristic of aspirin-induced hearing loss in auditory brainstem response
      of conscious rats.
AB  - The acute effects of aspirin on auditory functions were examined
      electrophysiologically in conscious rats with chronically implanted electrodes
      for auditory brainstem response (ABR) recording. A single intravenous injection
      of aspirin at a dose of 225 mg/kg caused a reduction in the amplitude of the ABR
      P1 wave evoked by a 2 kHz tone pip 1 and 24 hr after dosing at almost all sound
      intensity levels, while the P1 amplitude at 4 kHz was reduced mainly 1 hr after
      dosing, and the P1 amplitude at 8 kHz was not significantly affected at middle
      and high intensities even 1 hr after dosing. The audiogram obtained from the P1
      amplitude showed a significant increase in the sound threshold 1 and 24 hr after
      dosing at 2 kHz, and 1 hr after dosing at 4 kHz, but not at 8 kHz. The peak
      latency of the P1 wave was also prolonged. Furthermore, reduction of the P2 and
      P4 wave amplitude and prolongation of the P1-P2 and P2-P4 interpeak latency were
      also observed at 2 kHz but not a 4 or 8 kHz. These results suggest that the rat
      auditory function for low frequency is vulnerable to the effects of aspirin. This
      paradigm, i.e., frequency selectivity, n rats may be useful to further assess the
      different outer hair cells along the cochlear duct and provide additional
      evidence for the mechanism(s) or site underlying aspirin ototoxicity.

PMID- 9035072
TI  - Rapid apoptotic changes in the gastric glandular epithelium of rats administered
      intraperitoneally with fusarenon-X.
AB  - Fusarenon-X (FX) 1.5 mg/kg was administered intraperitoneally (i.p.) to 6-week
      old male Wistar rats for examination of pathologic effects on the glandular
      stomach. Rats ip-treated with sterilized physiological saline were used as
      control. FX-administered rats showed dilatation of the stomach with increased
      fluid contents after 1-4 hr. Light microscopically, a few apoptotic karyopyknosis
      were seen in chief cells in the basal region at 1 hr postadministration (PA) and
      mitotic inhibition was evident after 2 hr PA. Marked apoptosis of nuclear
      pyknosis and cytoplasmic inclusions in both zymogenic and oxyntic cells developed
      from basal to middle regions of the gastric mucous membrane at 2-4 hr PA with a
      peak at 3 hr. Apoptotic changes of differentiating neck cells and surface
      epithelia were less evident. Electron microscopy revealed that the chief cells
      were the main target of FX-induced apoptotosis. The parietal cells were
      secondarily involved because they phagocytosed chief cell-derived apoptotic
      bodies. In situ detection of DNA breaks by terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) reaction revealed the positive nuclei
      after 1 hr PA, which increased with time and reached a peak at 3 hr PA, in
      accordance with apoptotic changes in histological study. Agarose gel
      electrophoresis of DNA isolated from the gastric mucosae of FX-administered rats
      showed ladder pattern of DNA fragments after 1.5 hr PA with the maximum
      distinctness at 3 hr PA.

PMID- 9035073
TI  - Histological study of the seminiferous epithelium in the Japanese rat snake,
      Elaphe climacophora: identification of spermatogonium.
AB  - To clarify the features of the seminiferous epithelium of the Japanese rat snake,
      Elaphe climacophora, the identification of spermatogonium and the examination of
      features of cell to cell junctions were performed in the present study. As for
      the identification, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined
      immunohistochemically to mark spermatogonia. The seminiferous epithelium was
      observed throughout a year at the electron microscopic level. BrdU
      immunoreactivity was detected not only in the cells of the first layer of the
      seminiferous epithelium but also in the second and/or third layers. The cells
      immunoreactive in the first layer did not seem to attach to the basement membrane
      and were recognized throughout a year. To investigate cell to cell junctions, we
      performed actin filament detection by phalloidin staining. Distribution of actin
      filaments was different from that in mammalian species. At the ultrastructural
      level, Sertoli-Sertoli cell junctions were observed. Sertoli cells formed
      junctional complexes. Tight junctions were clearly found, but lacked the backing
      by actin filaments. These results indicate that the blood-testis barrier of the
      Japanese rat snake was structurally different from that of mammalian species. In
      conclusion, the seminiferous epithelium of the Japanese rat snake is intermediate
      in morphology between amphibians and mammals.

PMID- 9035074
TI  - Early serodiagnosis of porcine reproductive and respiratory syndrome virus
      infection of pigs by detection of slow-reacting and complement-requiring
      neutralizing antibody.
AB  - In order to evaluate and enhance the sensitivity of the neutralization (NT) test
      for detecting antibody in pigs infected with porcine reproductive and respiratory
      syndrome (PRRS) virus, the effect of altered incubation conditions and complement
      use on neutralizing (NT) antibody titer were investigated. Higher NT antibody
      titers were consistently obtained by addition of 20% guinea pig fresh serum to
      virus-serum mixtures in NT tests. Furthermore, the complement-requiring NT
      antibody titer increased in many serum samples when the virus-serum mixtures,
      rather than being incubated at 37 degrees C for 60 min, were incubated first at 4
      degrees C for 48 hr and then with a complement at 37 degrees C for 60 min. The
      slow-reacting and complement-requiring NT antibody was detected as early as 8
      days post-inoculation. It was detected in sera collected at 8 to 28 days post
      inoculation and was sensitive to 2-mercaptoethanol treatment. Sera collected at
      35 to 44 days post-inoculation contained 2-mercaptoethanol resistant NT
      antibodies. These results indicate that the modified NT test is useful for early
      serodiagnosis of PRRS virus infection through detection of higher NT antibody
      titers, and in detecting them earlier.

PMID- 9035075
TI  - Purification of the infectious bovine rhinotracheitis virus alkaline
      deoxyribonuclease expressed in Escherichia coli.
AB  - Nucleotide sequence analysis within the unique long segment of the infectious
      bovine rhinotracheitis virus (IBRV) genome identified an open reading frame of
      1461 base pairs whose deduced polypeptide of 487 amino acids exhibited homology
      to alkaline deoxyribonucleases of other herpesviruses. To determine whether this
      IBRV gene product has nuclease activity, the gene designated UL12 was inserted
      into the vector pET-28a(+) and expressed in Escherichia coli as an oligohistidine
      tagged protein. Upon induction with isopropyl beta-D-thiogalactopyranoside E.
      coli BL21 (DE3)[pLysS] cells harboring this recombinant plasmid produced a 57-kDa
      protein, the molecular mass of which was in accordance with the prediction from
      the nucleotide sequence. A one-step purification procedure using metal affinity
      chromatography resulted in a homogeneous preparation of this recombinant protein.
      The purified protein exhibited both exonuclease and endonuclease activities, each
      with an alkaline pH optimum.

PMID- 9035076
TI  - Establishment of a sandwich enzyme linked immunosorbent assay for canine
      interleukin-8.
AB  - To estimate canine interleukin-8 (cIL-8) levels in blood plasma samples, a
      sandwich enzyme linked immunosorbent assay (ELISA) was established. For the
      development of the sandwich ELISA, polyclonal anti-cIL-8 (capturing),
      biotinylated anti-cIL-8 (developing) antibodies and glutathione-S-transferase/cIL
      8 (GST/cIL-8) fusion protein as an antigen were used. cIL-8 in the fusion protein
      of GST/cIL-8 was detected in a dose dependent manner. The lowest limit of GST/cIL
      8 detectable by this method was 2 ng/ml of GST/cIL-8 (containing; 0.470 ng/ml of
      cIL-8). IL-8 levels in the plasma samples from apparently healthy dogs were less
      than 0.470 ng/ ml. Higher levels of IL-8 were detected in the plasma samples of
      dogs with cystitis, dermatitis, and gastric cancer. These results suggest that
      the determination of cIL-8 by the sandwich ELISA is useful in diagnosis of
      inflammatory diseases in dogs.

PMID- 9035077
TI  - Role of Bordetella bronchiseptica sialic acid-binding hemagglutinin as a putative
      colonization factor.
AB  - The role of Bordetella bronchiseptica sialic acid-binding hemagglutinin (SBHA) in
      bacterial colonization was studied by testing the ability of a phase-I strain
      carrying SBHA and its spontaneous mutants deficient in SBHA to colonize mouse
      tracheae. The mutants exhibited a remarkable reduction in colonizing ability,
      approximately 1,000-fold, when compared with that of the parent strain,
      suggesting that the possession of SBHA and the effective colonization by B.
      bronchiseptica organisms are closely related.

PMID- 9035078
TI  - Measurement of replicative DNA synthesis (RDS) by a 5-bromo-2'-deoxyuridine
      (BrdU) labeling technique for detection of hepatocyte proliferation.
AB  - The hypothesis has been proposed that cell proliferation, or replicative DNA
      synthesis (RDS) in S-phase cells, is a nongenotoxic (Ames-negative) mechanism
      involved in tumorigenesis, providing a very useful conceptual basis for
      carcinogen testing. In this present study, hepatocyte RDS experiments were
      conducted using 5-bromo-2'-deoxyuridine (BrdU) labeling in combination with
      histopathological observation, comparing our results with earlier findings for in
      situ [3H]thymidine (TdR) labeling. The present BrdU data proved to be consistent
      with the previous TdR data in all but one case. Hepatocyte RDS induction was
      observed for some chemicals without hepatotoxicity. BrdU labeling in combination
      with histopathological observation is therefore a reliable approach to assessment
      of test compound effects in vivo.

PMID- 9035079
TI  - Expression of the nucleocapsid protein gene of the canine distemper virus.
AB  - We constructed a cDNA clone of canine distemper virus (CDV) encoding an entire
      nucleoprotein (NP) gene, by means of the reverse transcription-polymerase chain
      reaction (RT-PCR). The cloned NP gene was inserted into the eucaryotic expression
      vector, pRVSV. After transfection of the plasmid into Vero cells, we examined the
      expression of CDV-specific NP antigen by means of indirect immunofluorescence
      assay (IFA) and Western blotting, using various antibodies against NP of CDV and
      an antiserum against NP of measles virus. The CDV-NP specific antigen was
      detected in the nuclei of the cells transfected with pRV-ON, by means of IFA with
      antibodies specific to the NP.

PMID- 9035080
TI  - Effect of Bordetella bronchiseptica and serotype D Pasteurella multocida bacterin
      toxoid on the occurrence of atrophic rhinitis after experimental infection with
      B. bronchiseptica and toxigenic type AP. multocida.
AB  - In efficacy tests, 7 primary specific-pathogen-free piglets vaccinated with the
      Bordetella bronchiseptica and type D Pasteurella multocida bacterin-toxoid were
      challenged with B. bronchiseptica and type A P. multocida. Severe or moderate
      nasal turbinate atrophy was produced in the non-vaccinated pigs, whereas, only
      one of the 4 pigs in the vaccinated group had slight turbinate atrophy. Other
      immune sera against crude toxin of P. multocida type A or D were cross
      neutralized. The results of the present study show that the P. multocida serotype
      D bacterin-toxoid is effective against atrophic rhinitis caused by toxigenic P.
      multocida serotype A as well as toxigenic P. multocida serotype D.

PMID- 9035081
TI  - Effect of ethylene thiourea on cultured rat embryos in the presence of hepatic
      microsomal fraction.
AB  - To investigate whether teratogenicity of ethylene thiourea (ETU) is due to ETU
      per se or to its metabolites, rat embryos cultured in vitro were exposed to 10
      and 30 micrograms/ml of ETU in the presence or absence of rat liver microsomal
      fraction (S9mix). In the absence of S9mix, the incidence of morphological
      abnormalities increased dose-dependently. In the presence of S9mix, abnormal
      morphogenesis was almost absent in all embryos. These findings suggest that
      teratogenicity of ETU is due to ETU per se.

PMID- 9035082
TI  - Earthquake damage to a laboratory animal facility.
AB  - Our seven-storey laboratory animal facility was damaged during the 1995
      earthquake of magnitude 7.2. The seismic intensity experienced at our facility
      was estimated to be around 5 on the Japanese version of the Richter scale (a very
      strong shock). However, no damage was sustained to the water, gas or electricity
      supplies in many of the offices, the upper drawers of the steel cabinets fell to
      the floor. In the animal-rooms, while the floor-fixed cage-racks were hardly
      damaged, most of the movable cage-racks were dislodged by the shocks. We describe
      here our countermeasures, including those taken prior to the earthquake.

PMID- 9035083
TI  - Resistance to UV-irradiation of DNA synthesis in fibroblast cell lines derived
      from LEC strain rats.
AB  - After UV-irradiation, no difference in the survival curves was observed among
      cell lines derived from LEC strain (LEC) rats and WKAH strain (WKAH) rats. The
      dose-response curves for inhibition of DNA synthesis in WKAH-derived cells showed
      a sharp decline at lower doses and a mild decline at higher doses of UV-rays. In
      contrast, the dose-response curves in LEC-derived cell lines had no sharp
      component, and were almost identical to the mild component of the curves in WKAH
      derived cells. These results show that DNA synthesis in the cell lines of LEC
      rats was more resistant to UV-irradiation than that of WKAH rats.

PMID- 9035084
TI  - Calcium metabolism in hypocalcemic cows with myocardial lesion.
AB  - This paper deals with blood levels of calcium (Ca), inorganic phosphorus,
      parathyroid hormone and 1,25-dihydroxyvitamin D in 6 cows treated for milk fever.
      Four of the cows stood within 1 day after Ca therapy, whereas 2 other cases
      showed an unsatisfactory response to Ca therapy and did not rise. The necropsy
      revealed microscopic necrotic myocardial lesions scattered in the heart of these
      2 unrecovered cows. The degree of hypocalcemia and hypophosphatemia were similar
      in the 6 cows. However, the recovery from hypophosphatemia was markedly delayed
      in the cows will an unsatisfactory response.

PMID- 9035086
TI  - Prevalence of Toxocara spp. eggs in sandpits of parks in Osaka city, Japan, with
      notes on the prevention of egg contamination by fence construction.
AB  - Toxocara spp. eggs were detected from 30 (75%) out of 40 sandpits of parks, in
      Osaka city. This prevalence was higher compared to those reported other areas of
      Japan. Since we examined a large quantity of sample, this could have resulted to
      higher prevalence. The number of eggs recovered decreased following fence
      construction around sandpits, but it did not sufficiently prevent the
      contamination of eggs. Improvement of fence design and education of sandpit users
      are necessary when contemplating fence construction around sandpits as a measure
      against contamination with Toxocara spp. eggs.

PMID- 9035085
TI  - Bacterial isolation from slaughtered pigs associated with endocarditis,
      especially the isolation of Streptococcus suis.
AB  - Bacterial isolation from slaughtered pigs with endocarditis was carried out from
      1985 to 1994. A total of 495 (0.025%) out of 2,006,127 pigs were diagnosed as
      having endocarditis. Though bacteria were significantly isolated from 399 of the
      495 pigs, bacteria could not be isolated in 96 pigs (19.4%). In 11 pigs, 2
      bacterial species were isolated from heart lesion. Streptococcus suis was
      isolated from 127 cases (25.7%), Streptococcus dysgalactiae from 75 (15.2%),
      Erysipelothrix rhusiopathiae from 63 (12.7%), Actinomyces pyogenes from 39
      (7.9%), Pasteurella multocida from 11 (2.2%). Staphylococcus aureus from 10
      (2.0%), and Streptococcus porcinus from 8 (1.6%). Among the 99 isolates
      biochemically identified as S. suis, the major serotype was S. suis type 2
      (35.4%). The remainder of the typable isolates were identified as serotypes 1/2
      (2.0%) and 9 (1.0%). A total of 61 isolates (61.6%) were untypable.

PMID- 9035088
TI  - Direct detection of Campylobacter jejuni in chicken cecal contents by PCR.
AB  - Campylobacter jejuni in chicken feces was detected by PCR and Southern blot
      hybridization (SBH). The detection limits of C. jejuni in chicken feces were
      34,000 cells by PCR and 340 cells by SBH. Some cecal contents of chickens up to 3
      weeks old were C. jejuni positive by SBH whereas all of them were negative by
      PCR. Two of 51 cecal contents of 18-day-old chicken embryos were C. jejuni
      positive by PCR and SBH; but, C. jejuni were not isolated from the samples by
      conventional culture with selective enrichment.

PMID- 9035087
TI  - Tastes activate different second messengers in taste cells.
AB  - Taste signal transduction occurs in the microvillous membrane of taste cells.
      Previously, we hypothesized that c-GMP may mediate sweet taste transduction. Some
      data indicated that IP3 may have a role in vertebrate bitter taste transduction.
      Here we report that the different second messengers are activated by different
      tastes. We used techniques designed for radioimmunoassay measurement. The results
      indicate that sucrose triggers an increase in c-GMP concentration and quinine
      increases the IP3 concentration in mouse taste cells. These results support the
      sweet and bitter taste transduction hypotheses.

PMID- 9035089
TI  - The FDA: a dromedary tale.

PMID- 9035090
TI  - Transgenic bagels and neurotic genes.

PMID- 9035091
TI  - Commissioner Kessler's agbio legacy.

PMID- 9035092
TI  - What lies beyond bioinformatics?

PMID- 9035093
TI  - Kessler's departure from FDA gets mixed response.

PMID- 9035094
TI  - NIHRAC: disguised retirement or vigorous future?

PMID- 9035095
TI  - Boehringer networks to get ahead in gene therapy.

PMID- 9035096
TI  - Experts attempt to redefine principles for treating HIV.

PMID- 9035097
TI  - Safe gene vectors made simpler.

PMID- 9035098
TI  - E. coli moves into the plastic age.

PMID- 9035100
TI  - Amyloid hypothesis of Alzheimer's rides high--for now.

PMID- 9035099
TI  - Antitumor immunotoxin secretion by T cells: ABSolutely FABulous?

PMID- 9035101
TI  - The empire strikes back.

PMID- 9035102
TI  - Display of heterologous proteins on the surface of microorganisms: from the
      screening of combinatorial libraries to live recombinant vaccines.
AB  - In recent years there has been considerable progress towards the development of
      expression systems for the display of heterologous polypeptides and, to a lesser
      extent, oligosaccharides on the surface of bacteria or yeast. The availability of
      protein display vectors has in turn provided the impetus for a range of exciting
      technologies. Polypeptide libraries can be displayed in bacteria and screened by
      cell sorting techniques, thus simplifying the isolation of proteins with high
      affinity for ligands. Expression of antigens on the surface of nonvirulent
      microorganisms is an attractive approach to the development of high-efficacy
      recombinant live vaccines. Finally, cells displaying protein receptors or
      antibodies are of use for analytical applications and bioseparations.

PMID- 9035103
TI  - Bioactive murine and human interleukin-12 fusion proteins which retain antitumor
      activity in vivo.
AB  - Interleukin-12 (IL-12) is unique amongst cytokines in being a disulfide-linked
      heterodimer of two separately encoded subunits (p35 and p40). We expressed single
      chain IL-12 proteins from retroviral constructs in which the two IL-12 subunits
      were linked by a 6-15 amino acid polypeptide linker, with deletion of the 22
      amino acid leader sequence of the trailing subunit. The murine fusion protein IL
      12.p40.L.delta p35 containing a (Gly4Ser)3 linker was stably expressed, bioactive
      in vitro, and had an apparent specific activity comparable to that of native and
      recombinant IL-12. Western blotting confirmed that murine IL-12.p40.L.delta p35
      retained the linking polypeptide sequences. The analogous human IL-12.p40.L.delta
      p35 fusion protein containing a Gly6Ser linker was bioactive with an apparent
      specific activity comparable to recombinant human IL-12. In a preexisting CMS-5
      tumor model, CMS-5 cells secreting either native or fusion protein forms of IL-12
      prolonged survival and led to complete tumor regression.

PMID- 9035104
TI  - Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine
      receptors from myasthenic antibodies.
AB  - The muscular weakness and fatigability associated with myasthenia gravis are
      engendered by autoantibodies directed against acetylcholine receptors on muscle
      cells at neuromuscular junctions. The pathogenic consequences of this immune
      response can potentially be modulated by molecules that bind such autoantibodies
      and block their interaction with these receptors. We report the isolation of a
      small nuclease-resistant RNA molecule that binds both a rat monoclonal antibody
      that recognizes the main immunogenic region on the acetylcholine receptor, and
      autoantibodies from patients with myasthenia gravis. Moreover, this RNA can act
      as a decoy and protect acetylcholine receptors on human cells from the effects of
      these antibodies.

PMID- 9035106
TI  - Adenovirus dodecahedron, a new vector for human gene transfer.
AB  - Recombinant adenovirus is one of most efficient delivery vehicles for gene
      therapy. However, the initial enthusiasm for the use of recombinant adenovirus
      for gene therapy has been tempered by strong immune responses that develop to the
      virus and virus-infected cells. Even though recombinant adenoviruses are
      replication-defective, they introduce into the recipient cell, together with the
      gene of interest, viral genetes that might lead to fortuitous recombination if
      the recipient is infected by wild-type adenovirus. We propose the use of a
      dodecahedron made of adenovirus pentons or penton bases as an alternative vector
      for human gene therapy. The penton is a complex of two oligomeric proteins, a
      penton base and fiber, involved in the cell attachment, internalization, and
      liberation of virus into the cytoplasm. The dodecahedron retains many of the
      advantages of adenovirus for gene transfer such as efficiency of entry, efficient
      release of DNA from endosomes, and wide range of cell and tissue targets. Because
      it consists of only one or two adenovirus proteins instead of the 11 contained in
      an adenovirus virion and it does not contain the viral genome, it is potentially
      a safer alternative to recombinant adenovirus.

PMID- 9035105
TI  - A new class of antigen-specific killer cells.
AB  - A new class of antigen-specific killer cells that combines the features of
      antibody-mediated and cell-mediated immunity was designed. The principle and
      feasibility of this strategy are illustrated by creating an antigen-specific
      killer cell to produce and secrete targeted antibody-toxin molecules that
      recognize and kill human immunodeficiency virus (HIV)-1-infected cells. The
      transduced lymphocytes, which were able to produce and secrete the targeted toxin
      proteins, remained viable due to the lack of the target antigen on the cell
      surface. These transduced cells were found to have selective and potent
      cytotoxicity to the HIV-infected cells. This approach combines the specificity of
      antibodies, extreme potency of toxins, and effector-cell properties of T-cells to
      generate a new class of potent antigen-specific killer cells, which may have
      broad applications for the treatment of viral infection and other diseases. This
      study demonstrates the principle that mammalian cells can be genetically modified
      to produce targeted toxins, indicating that in vivo production of targeted toxins
      can be achieved to locally or systematically destroy targeted cells.

PMID- 9035109
TI  - Potent 2'-amino-, and 2'-fluoro-2'-deoxyribonucleotide RNA inhibitors of
      keratinocyte growth factor.
AB  - Reiterative in vitro selection-amplification from random oligonucleotide
      libraries allows the identification of molecules with specific functions such as
      binding to specific proteins. The therapeutic usefulness of such molecules
      depends on their high affinity and nuclease resistance. Libraries of RNA
      molecules containing 2'amino-(2'NH2)- or 2'fluoro-(2'F)-2'-deoxypyrimidines could
      yield ligands with similar nuclease resistance but not necessarily with similar
      affinities. This is because the intramolecular helices containing 2'NH2 have
      lower melting temperatures (Tm) compared with helices containing 2'F, giving them
      thermodynamically less stable structures and possibly weaker affinities. We
      tested these ideas by isolating high-affinity ligands to human keratinocyte
      growth factor from libraries containing modified RNA molecules with either 2'NH2
      or 2'F pyrimidines. We demonstrated that 2'F RNA ligands have affinities (Kd
      approximately 0.3-3 pM) and bioactivities (Ki approximately 34 pM) superior to
      2'NH2 ligands (Kd approximately 400 pM and Ki approximately 10 nM). In addition,
      2'F ligands have extreme thermo-stabilities (Tm approximately 78 degrees C in low
      salt, and specificities).

PMID- 9035108
TI  - PHA synthase activity controls the molecular weight and polydispersity of
      polyhydroxybutyrate in vivo.
AB  - A synthetic operon for polyhydroxyalkanoate (PHA) biosynthesis designed to yield
      high levels of PHA synthase activity in vivo was constructed by positioning a
      genetic fragment encoding beta-ketothiolase and acetoacetyl-CoA reductase behind
      a modified synthase gene containing an Escherichia coli promoter and ribosome
      binding site. Plasmids containing the synthetic operon and the native Alcaligenes
      eutrophus PHA operon were transformed into E. coli DH5 alpha and analyzed for
      polyhydroxybutyrate production. The molecular weight of polymer isolated from
      recombinant E. coli containing the modified synthase construct, determined by
      multiangle light scattering, was lower than that of the polymer from E. coli
      containing the native A. eutrophus operon. A further decrease in polyester
      molecular weight was observed with increased induction of the PHA biosynthetic
      genes in the synthetic operon. Comparison of the enzyme activity levels of PHA
      biosynthetic enzymes in a strain encoding the native operon with a strain
      possessing the synthetic operon indicates that the amount of polyhydroxyalkanoate
      synthase in a host organism plays a key role in controlling the molecular weight
      and the polydispersity of polymer.

PMID- 9035107
TI  - Nerve growth factor somatic mosaicism produced by herpes virus-directed
      expression of cre recombinase.
AB  - Focal molecular genetic alteration of the intact mammalian brain will be required
      to elucidate gene product function in cells comprising synaptic networks. To this
      end, a somatic mosaic approach has been developed for the mouse whereby a dormant
      germline transgene is activated by the somatic delivery and expression of cre
      recombinase. Transgenic mice harboring a recombinational substrate, the germline
      transmitted nerve growth factor excision activation transgene (NGF-XAT) were
      generated. Somatic delivery of virus vectors expressing cre recombinase into the
      brain of NGF-XAT mice resulted in regional recombination and activation of the
      transgene as demonstrated at the DNA level by PCR and at the protein level by
      both immunocytochemistry and ELISA. This approach has been used to evaluate a
      behavioral correlate of unilateral NGF mosaicism within the dorsal hippocampal
      formation. NGF-XAT mice activated by expression of cre recombinase manifest
      increased locomotor activity compared with NGF-XAT mice transduced by a control
      virus expressing Escherichia coli beta-galactosidase. These data indicate that
      focally increased expression of NGF in one part of a synaptic network can elicit
      changes in behavior presumably by altering the overall function of NGF-responsive
      neural circuitry. This approach should have broad application to other gene
      products and promises to provide the unprecedented ability to create and study
      discrete genetic modifications in the context of an intact adult mammal.

PMID- 9035110
TI  - Efficient epitope mapping by bacteriophage lambda surface display.
AB  - A bacteriophage lambda surface expression system, lambda foo, was used for
      epitope mapping of human galectin-3. We constructed random epitope and peptide
      libraries and compared their efficiencies in the mapping. The galectin-3 cDNA was
      randomly digested by DNase 1 to make random epitope libraries. The libraries were
      screened by affinity selection using a microtiter plate coated with monoclonal
      antibodies. Direct DNA sequencing of the selected clones defined two distinct
      epitope sites consisting of nine and 11 amino-acid residues. Affinity selection
      of random peptide libraries recovered a number of sequences that were similar to
      each other but distinct from the galectin-3 sequence. These results demonstrate
      that a single affinity selection of epitope libraries with antibodies is able to
      define an epitope determinant as small as nine residues long and is more
      efficient in epitope mapping than random peptide libraries.

PMID- 9035111
TI  - Functional antibody production using cell-free translation: effects of protein
      disulfide isomerase and chaperones.
AB  - To create a rapid system to test the effect of sequence changes on recombinant
      antibody binding, we have developed a procedure for producing functional scFv
      fragments in an Escherichia coli cell-free translation system. Functional
      antibodies with antigen-binding activity are obtained only if disulfide formation
      and rearrangement is allowed to take place during the translation reaction. The
      inclusion of protein disulfide isomerase (PDI) leads to a threefold increase in
      yield over that obtained in the presence of glutathione redox systems. DsbA had
      no such effect, indicating that disulfide shuffing, and not net formation, is the
      crucial yield-limiting step. The addition of the molecular chaperones DnaK and
      DnaJ increased the amount of soluble protein but not the amount of functional
      scFv, which appears to be limited entirely by correct disulfide formation. None
      of these factors significantly influenced total protein synthesis. In the
      presence of PDI, chaperones, reduced glutathione and oxidized glutathione, 50% of
      the scFv produced (about 8 micrograms/ml in only 15 min) could be recovered from
      immobilized antigen.

PMID- 9035112
TI  - Beyond the letter of the law: the US Federal Circuit interprets section 271(g)(1)

PMID- 9035113
TI  - Investing in risk management.

PMID- 9035114
TI  - Protein databases on the WWW.

PMID- 9035115
TI  - Gene therapy: the US FTC explains it all to you.

PMID- 9035116
TI  - Miami Winter Symposium gets back to basics.

PMID- 9035117
TI  - Biotechnology, bioremediation, and blue genes.

PMID- 9035118
TI  - The end of big government?

PMID- 9035119
TI  - Genetically enhanced food for thought.

PMID- 9035120
TI  - Warner Lambert/Sankyo diabetes drug nears market.

PMID- 9035121
TI  - Boehringer Mannheim's new clot buster.

PMID- 9035122
TI  - Vysis leukemia diagnostic approved.

PMID- 9035123
TI  - Bioject's painless injections.

PMID- 9035124
TI  - Aerosol CF gene therapy "safe and efficient".

PMID- 9035125
TI  - GI-AHP deal may catalyze more big-time acquisitions.

PMID- 9035126
TI  - Novartis licenses gene therapy to avoid monopoly.

PMID- 9035127
TI  - EC-FDA mutual recognition agreement proves difficult.

PMID- 9035128
TI  - "Ganske" threatens biotechnology patents worldwide.

PMID- 9035129
TI  - Genomics companies welcome US PTO initiative on DNA patents.

PMID- 9035130
TI  - Reflections on internal images.

PMID- 9035131
TI  - Tipping the balance of blood coagulation.

PMID- 9035132
TI  - Mix and match: building manifold binding sites.

PMID- 9035133
TI  - Phytoremediation: a clean transition from laboratory to marketplace?

PMID- 9035134
TI  - Carboxypeptidase e: a surprise player in protein sorting.

PMID- 9035135
TI  - Approval times for supplemental indications for recombinant proteins.

PMID- 9035136
TI  - A new class of viral inhibitor.

PMID- 9035137
TI  - Transgenic plants: an emerging approach to pest control.
AB  - Insect pests are a major cause of damage to the world's commercially important
      agricultural crops. Current strategies aimed at reducing crop losses rely
      primarily on chemical pesticides. Alternatively transgenic crops with intrinsic
      pest resistance offer a promising alternative and continue to be developed. The
      first generation of insect-resistant transgenic plants are based on insecticidal
      proteins from Bacillus thuringiensis (Bt). A second generation of insect
      resistant plants under development include both Bt and non-Bt proteins with novel
      modes of action and different spectra of activity against insect pests.

PMID- 9035138
TI  - I. A bioactive designer cytokine for human hematopoietic progenitor cell
      expansion.
AB  - Efficient expansion of hematopoietic progenitor cells requires, at least, the
      simultaneous stimulation of the receptors c-kit and gp130. While c-kit is
      activated by SCF; gp130, in cells which do not express sufficient amounts of IL
      6R, can be activated by the complex of soluble IL-6R (sIL-6R) and IL-6. The
      therapeutic use of IL-6/sIL-6R, however, has been hampered by the high
      concentrations of the sIL-6R protein required. We have designed a fusion protein
      of sIL-6R and IL-6, linked by a flexible peptide chain, that was expressed to
      high levels. On gp130 expressing cells the fusion protein turned out to be fully
      active at 100 to 1,000-fold lower concentration than the combination of unlinked
      IL-6 and IL-6R. The fusion protein was used to effectively expand human
      hematopoietic progenitor cells ex vivo in a dose dependent fashion.

PMID- 9035139
TI  - Rational engineering of activity and specificity in a serine protease.
AB  - The discovery of the Na(+)-dependent allosteric regulation in serine proteases
      makes it possible to control catalytic activity and specificity in this class of
      enzymes in a way never considered before. We demonstrate that rational site
      directed mutagenesis of residues controlling Na+ binding can profoundly after the
      properties of a serine protease. By suppressing Na+ binding to thrombin, we shift
      the balance between procoagulant and anticoagulant activities of the enzyme.
      Those mutants, compared to wild-type, have reduced specificity toward fibrinogen,
      but enhanced or slightly reduced specificity toward protein C. Because this
      engineering strategy targets a fundamental regulatory mechanism, it is amenable
      of extension to other enzymes of biological and pharmacological importance.

PMID- 9035140
TI  - Synthetic CD4 exocyclics inhibit binding of human immunodeficiency virus type 1
      envelope to CD4 and virus replication in T lymphocytes.
AB  - CD4 functions as a major T-cell surface receptor for human immunodeficiency virus
      by binding the human immunodeficiency virus type 1 (HIV-1) envelope protein gp120
      with relatively high affinity. We have developed constrained aromatically
      modified analogs of the secondary structures of the first domain of CD4 in order
      to analyze surfaces involved in binding of gp120. Complementarity determining
      like regions (CDRs) of the D1 domain of CD4 were reproduced as synthetic
      aromatically modified exocyclic (AMEs) forms. The exocyclic CDR3.AME(82-89),
      derived from the CDR3 (residues 82-89) region of CD4 D1 domain, specifically
      inhibited binding of recombinant gp120 to both recombinant soluble CD4, and CD4+
      Jurkat cells, and blocked syncytium formation and virus particle production
      caused by HIV-1 infection. We have previously shown that the CDR3.AME analog
      binds to the CD4 CDR3 region and creates a disabled CD4 heterodimer. We propose
      that the AME prevents the formation of an essential homodimeric surface needed
      for efficient HIV binding. Additionally the disabled CD4 receptor may be less
      able to signal the cell to allow HIV replication and HIV infection. Such
      compounds may represent a new receptor specific approach to modulate biological
      functions.

PMID- 9035141
TI  - Therapeutic potential of antiidiotypic single chain antibodies with yeast killer
      toxin activity.
AB  - Single chain fragment (ScFv) antiidiotypic antibodies (antilds) of a killer toxin
      (KT) from the yeast Pichia anomala have been produced by recombinant DNA
      methodology from the splenic lymphocytes of mice immunized by idiotypic
      vaccination with a KT-neutralizing monoclonal antibody (Mab KT4). ScFv KT-like
      antilds (KTIdAb) react with specific Candida albicans KT cell wall receptors
      (KTR) exerting a candidacidal activity in vitro could be neutralized by
      adsorption with Mab KT4. ScFv KTIdAb displayed an effective therapeutic activity
      in an experimental model of rat candidal vaginitis.

PMID- 9035142
TI  - Design and production of novel tetravalent bispecific antibodies.
AB  - We have produced novel bispecific antibodies by fusing the DNA encoding a single
      chain antibody (ScFv) after the C terminus (CH3-ScFv) or after the hinge (Hinge
      ScFv) with an antibody of a different specificity. The fusion protein is
      expressed by gene transfection in the context of a murine variable region.
      Transfectomas secrete a homogeneous population of the recombinant antibody with
      two different specificities, one at the N terminus (anti-dextran) and one at the
      C terminus (anti-dansyl). The CH3-ScFv antibody, which maintains the constant
      region of human IgG3, has some of the associated effector functions such as long
      half-life and Fc receptor binding. The Hinge-ScFv antibody which lacks the CH2
      and CH3 domains has no known effector functions.

PMID- 9035143
TI  - Electrically induced NGF production by astroglial cells.
AB  - A controlled culture system has been developed to induce nerve growth factor
      (NGF) production in astroglial cells that are cultured on an electrode surface.
      The electrode potential is alternatively modulated at an amplitude of 300 mV and
      a frequency of 10 Hz. The electric stimulation triggers NGF production and
      secretion. The mechanism of the electrically induced NGF production is discussed
      in association with protein kinase C (PKC) activation.

PMID- 9035144
TI  - Factors influencing the efficiency of cationic liposome-mediated intravenous gene
      delivery.
AB  - We have characterized the relationships between the design of cationic liposomes
      as a gene transfer vehicle, their resulting biodistribution and processing in
      animals, and the level and sites of gene expression they produce. By redesigning
      conventional cationic liposomes, incorporating cholesterol (chol) as the neutral
      lipid and preparing them as multilamellar vesicles (MLV), we increased the
      efficiency of cationic liposome:DNA complex (CLDC)-mediated gene delivery.
      Expression of the luciferase gene increased up to 1,740-fold and of the human
      granulocyte-colony stimulating factor (hG-CSF) gene up to 569-fold due to
      prolonged circulation time of injected CLDC, and increased uptake and retention
      in tissues. The level of gene expression per microgram of DNA taken up per tissue
      was 1,000-fold higher in lung than in liver, indicating that in addition to
      issues of delivery and retention of injected DNA, tissue-specific host factors
      also play a central role in determining the efficiency of expression. Vascular
      endothelial cells, monocytes, and macrophages are the cell types most commonly
      transfected by intravenous injection of CLDC.

PMID- 9035145
TI  - Plant cell biodegradation of a xenobiotic nitrate ester, nitroglycerin.
AB  - The ability of plants to metabolize the xenobiotic nitrate ester, glycerol
      trinitrate (GTN, nitroglycerin), was examined using cultured plant cells and
      plant cell extracts. Intact cells rapidly degrade GTN with the initial formation
      of glycerol dinitrate (GDN) and the later formation of glycerol mononitrate
      (GMN). A material balance analysis of these intermediates indicates little, if
      any, formation of reduced, conjugated or cell-bound carbonaceous metabolites.
      Cell extracts were shown to be capable of degrading GTN with the simultaneous
      formation of GDN in stoichiometric amounts. The intermediates observed, and the
      timing of their appearance, are consistent with a sequential denitration pathway
      that has been reported for the microbial degradation of nitrate esters. The
      degradative activities of plant cells are only tenfold less than those reported
      for bacterial GTN degradation. These results suggests that plants may serve a
      direct degradative function for the phytoremediation of sites contaminated by
      organic nitrate esters.

PMID- 9035146
TI  - Phytoplasma induced free-branching in commercial poinsettia cultivars.
AB  - Free-branching poinsettia cultivars that produce numerous axillary shoots are
      essential for propagating desirable multi-flowered poinsettias (Euphorbia
      pulcherrima Wild. Klotz). For more than a decade, a biological agent has been
      suspected to cause free-branching in poinsettias. Attempts to identify the
      branching agent have failed. Isolation of the pathogen was accomplished using a
      living host and it was concluded that an unculturable phytoplasma is the cause of
      free-branching in poinsettias. This is the first reported example of a pathogenic
      phytoplasma as the causal agent of a desirable and economically important trait.

PMID- 9035147
TI  - Going beyond the native: protecting DNA and protein patents.

PMID- 9035162
TI  - Persistent hypercalciuria and elevated 25-hydroxyvitamin D3 in children with
      infantile hypercalcaemia.
AB  - The aim of the study was to characterize abnormalities of calcium-phosphate and
      vitamin D3 metabolism in children with a past history of "mild" Lightwood-type
      idiopathic infantile hypercalcaemia. Seventeen seemingly healthy children aged 2
      12 years, with long-term idiopathic hypercalcaemic syndrome since infancy were
      studied. Two reference groups were also included (vitamin D3 intoxication/healthy
      and Williams groups). Despite a long-term milk-restricted diet and a restricted
      vitamin D3 intake, urinary calcium excretion in the study group was 0.117 +/-
      0.07 mumol/kg per 24 h. Compared with the reference groups (0.047 +/- 0.029 and
      0.067 +/- 0.06 mumol/kg per 24 h, P < 0.05), there was significant hypercalciuria
      in the children with idiopathic hypercalcaemia since infancy. Serum
      concentrations of 25-hydroxyvitamin D3 in the study group were also elevated
      compared with the reference groups (57.4 +/- 15.5 vs. 34.6 +/- 9.3 and 22.7 +/-
      10.5 ng/ml). 1,25-Dihydroxyvitamin D3 levels were at the upper limit of normal
      (45.9 +/- 13.1 vs. 35.0 +/- 8.1 and 30.0 +/- 13.7 pg/ml). Non-progressive,
      clinically silent nephrocalcinosis was visible on ultrasound examinations. The
      disturbances of vitamin D3 and calcium-phosphate metabolism persistent in the
      normocalcaemic phase of idiopathic infantile hypercalcaemia may be a primary
      metabolic defect of the condition. The mechanisms leading to elevation of
      metabolites of 1,25-dihydroxy- and 25-hydroxyvitamin D3 and the relationship
      between this and persistent hypercalciuria and nephrocalcinosis need
      pathophysiological explanation.

PMID- 9035163
TI  - Liddle's syndrome: a 14-year follow-up of the youngest diagnosed case.
AB  - The 14-year follow-up of a female patient with Liddle's syndrome (LS), a rare
      disease characterized by hypertension, hypokalemic alkalosis, and negligible
      aldosterone secretion due to renin suppression, is described. The disease was
      diagnosed at the age of 10 months (youngest identification). The patient was
      repeatedly investigated during follow-up for plasma renin activity (PRA), plasma
      aldosterone concentration (PA), serum sodium and potassium (K) concentration,
      blood pressure (BP), somatic anthropometry, and mental development. Noteworthy
      results included: persistent low circulating K, PRA, and PA and high BP,
      coinciding with unauthorized withdrawal of the triamterene therapy. These
      findings are in keeping with the hypothesis that LS results from a pathogenetic
      disorder which is not correctable with age. The triamterene therapy was effective
      in correcting the endocrine and metabolic disorders as well as arterial
      hypertension, but did not prevent a deficit in mental and physical development.
      However, the information derived from this study allows further clarification of
      the clinical picture of the disease.

PMID- 9035164
TI  - Acute interstitial nephritis associated with IgA nephropathy in children.
AB  - IgA nephropathy (IgAN) is a relatively common glomerulopathy in children and
      adolescents. The etiology of this disease is uncertain. We previously reported a
      child with IgAN who developed acute interstitial nephritis. We now describe three
      pediatric patients, including the index case, who had IgAN and who developed
      concomitant acute interstitial nephritis in association with renal functional
      impairment. We suggest that this histopathological lesion be considered in any
      child with IgAN and unexpectedly severe kidney dysfunction.

PMID- 9035165
TI  - HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic
      syndrome.
AB  - There is a lack of reliable predictors of the response to alkylating agents in
      children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated
      with the frequency of relapses in steroid-sensitive NS before cytostatic therapy.
      We therefore examined retrospectively the time to the first relapse and the
      incidence of subsequent relapses in 54 HLA-typed children with frequently
      relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n =
      5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80%
      in both groups being steroid dependent. HLA typing was performed using
      serological or DNA typing methods. Renal biopsy showed minimal glomerular
      changes. A lower proportion of HLA-DR7 positive than negative patients remained
      in remission after 3 years (36% vs. 81%, P < 0.02) and 5 years (36% vs. 72%, P <
      0.03). In the first 3 years after cytostatic therapy the mean number of
      prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients
      compared with 0.4 in negative patients (P < 0.025). There was no statistically
      significant difference in the proportion of relapse-free patients with and
      without steroid dependency. The HLA status predicts the response of NS patients
      to alkylating agents better than the rate of previous relapses.

PMID- 9035166
TI  - Superior vena cava thrombosis and chylothorax: relationship in pediatric
      nephrotic syndrome.
AB  - We report a 40-month-old black male with nephrotic syndrome who developed
      chylothorax associated with superior vena cava (SVC) thrombosis. To our
      knowledge, this is the third reported case of spontaneous SVC thrombosis in a
      nephrotic patient and the first in which chylothorax was also present.
      Ultrasonography of the pleura and thoracic vasculature was invaluable in making
      the diagnosis and monitoring the resolution of this condition during treatment.
      Contrary to previous reports, thoracic chylous effusions complicating
      uncontrolled nephrotic syndrome do not originate exclusively as a consequence of
      abdominal pathology, but rather as this case demonstrates, they can occur from
      lymphatic obstruction caused by thoracic vein thrombosis.

PMID- 9035167
TI  - Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after
      renal transplantation.
AB  - Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged
      6.3-24.3 (median 15.0) years who had been transplanted 1.5-8.4 years previously.
      Daytime values were compared with the mean of 10 concomitant casual blood
      pressure recordings. At the time of the study, antihypertensive drugs were given
      to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per
      1.73 m2. Ambulatory blood pressure monitoring confirmed hypertension or
      normotension determined by casual blood pressure measurements in 63% of patients.
      The physiological nocturnal dip in blood pressure was attenuated or reversed in 8
      of 27 patients. It was reduced in all 3 patients with renal artery stenosis of
      the graft, in 3 of 4 patients with chronic rejection, in the only patient with
      recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past
      acute rejection. The dipping was not related to inulin clearance. In conclusion,
      casual blood pressure measurements do not accurately reflect blood pressure in
      pediatric patients transplanted more than 1.5 years previously. A reduced
      nocturnal dip in blood pressure may indicate an underlying renovascular or
      renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly
      be applied in patients with renal transplants.

PMID- 9035168
TI  - Value of Doppler ultrasound for the diagnosis of renal artery stenosis in
      children.
AB  - To evaluate the reliability of Doppler ultrasonography (US) in identifying
      children with renal artery stenosis (RAS) among those with hypertension, we
      compared Doppler US results in 22 hypertensive children (mean age 8.9 +/- 4.3
      years), with (13 cases) and without RAS at angiography, and in 33 normotensive
      children (mean age 8.8 +/- 4.7 years). We observed 2 false-negatives and 2 false
      positives with Doppler US. Of the 2 false-negative diagnoses, I had RAS on an
      accessory renal artery located behind a normal upper polar artery and the other
      was observed in a patient with bilateral multiple stenosis of the very distal
      segments of renal arteries. The 2 false-positive diagnoses were due to sinuous
      left renal artery and to technical reasons, respectively. In another patient,
      Doppler US showed a tight RAS, while arteriography was normal. RAS was
      subsequently confirmed by a second arteriography. Peak systolic velocity values
      of Doppler US were significantly higher in patients with proven angiographic RAS
      (3.44 +/- 0.66 m/s) than in hypertensive patients with normal renal arteries at
      angiography (0.99 +/- 0.35 m/s, P < 0.0001) and normotensive healthy children
      (1.04 +/- 0.23 m/s, P < 0.0001). With the use of multiple views, and the
      experience acquired with practice, false-negatives or false-positives due to the
      geometry of the renal artery can be avoided. Nevertheless, very distal stenosis
      can be missed by Doppler US.

PMID- 9035169
TI  - Renal involvement in the Laurence-Moon-Bardet-Biedl syndrome: report of five
      cases.
AB  - We report five patients with Laurence-Moon-Bardet-Biedl syndrome (LMBBS) who had
      renal involvement. Intravenous pyelography showed bilateral or unilateral
      calyceal clubbing and blunting in all patients. In addition, one patient had a
      parapelvic cyst in the left kidney and another had bilateral lobulated renal
      outlines of the fetal type. One patient had a urinary concentrating defect and
      two patients showed increased fractional sodium excretion. Estimated tubular
      phosphate reabsorption values were in normal limits in all of five patients. No
      patient had a urine acidification defect, proteinuria, glycosuria, or
      hyperaminoaciduria. One patient died from end-stage renal failure. The remaining
      four patients had normal serum creatinine values and estimated creatinine
      clearances. 99mTechnetium-diethylenetriamine pentaacetate renal scanning showed
      prolonged and delayed concentration and delayed excretion in three of the four
      patients who survived. A focal scar was determined on the left kidney of one of
      four patients by 99mtechnetium-dimercaptosuccinic acid renal scanning. All LMBBS
      cases with or without renal symptoms should be routinely evaluated for renal
      abnormalities. Renal scanning is a valuable method, especially for determining
      the renal involvement in the early stage of disease.

PMID- 9035170
TI  - Possible person-to-person transmission of Escherichia coli O111--associated
      hemolytic uremic syndrome.
AB  - Over a 3-month period, ten children (aged 1-13 years) from a 15-km radius in
      southern Picardy developed typical D+ hemolytic uremic syndrome (HUS). Polymerase
      chain reaction, using two pairs of verocytotoxin 1-(VT1) and VT2-specific
      oligonucleotide primers and an internal control was used to detect VT genes
      directly from stools samples. VT2 gene was detected in seven of nine patients'
      stools and in 5 of 14 contacts' stool samples. A VT2-producing Escherichia coli
      (VTEC) O111 was isolated from five of nine children's stools and in 3 adults'
      stools of the 14 tested. A retrospective case-control study was performed which
      showed a higher rate of absence in school A, where the first four cases were
      detected, compared with a control school. The odds ratio for the whole school was
      2.77 (confidence interval 1.46-5.26), and 15 (confidence interval 2.54-115.6) if
      only the nursery classes were considered. A culture of all food samples from
      households was always negative for VTEC. A retrospective cohort study performed
      in 89% of children attending school A showed no linkage between food or drink and
      gastroenteritis. These findings emphasize the potential for person-to-person
      transmission of VT2-producing E. coli O111, since the only salient risk factor
      was close contact.

PMID- 9035171
TI  - Body growth in primary de Toni-Debre-Fanconi syndrome.
AB  - Body growth in nine children with primary de Toni-Debre-Fanconi syndrome was
      followed from birth to adolescence or adult life. At the time of diagnosis,
      corresponding to the start of treatment, the median age was 2.3 (range 0.4-13.9)
      years and height standard deviation score (SDS) was always decreased (median 
      3.5, range -6.8 to -2.1). Despite continuous electrolyte and bicarbonate
      supplementation only four patients showed a slight improvement in growth. At the
      time of the last observation at the age of 17.2 (4.5-20.1) years median height
      was -4.7 (-5.9 to -1.8) SDS. The median difference between height at last
      observation and target height was -4.5 SDS. Final height (n = 5) ranged between 
      1.8 and -5.5 (median -4.3) SDS. The pubertal growth spurt was absent in two
      children. Metabolic acidosis was identified as a significant growth-retarding
      factor. Mean serial blood bicarbonate levels and height SDS at the last
      observation were correlated (r = -0.87, P < 0.01). No correlation was observed
      between last height SDS and the degree of hypokalemia, hypophosphatemia, or
      hypercalciuria. In conclusion, patients with primary de Toni-Debre-Fanconi
      syndrome present severe growth failure at the time of diagnosis which persists
      into adult life. Supportive therapy is frequently unable to prevent further loss
      of relative height.

PMID- 9035172
TI  - Effect of extreme prematurity on renal dopamine and norepinephrine excretion
      during the neonatal period.
AB  - Dopamine (DA), produced in proximal tubular cells, is believed to be an important
      intrarenal natriuretic hormone. Experimental studies have shown that the
      natriuretic effect of DA is less pronounced in the fetal kidney. We have
      evaluated renal DA and norepinephrine (NE) in the neonatal period, using urinary
      excretion as an indicator of renally produced/released-catecholamines. In very
      low-birth-weight infants (25-30 weeks gestational age) there was an increase in
      urinary DA (pmol/mumol urinary creatine) and NE (pmol/mumol urinary creatinine)
      from 1 to 13 days postnatal age, despite a decrease in sodium excretion. Urinary
      NE correlated with plasma NE, whereas plasma DA was undetectable. In summary, NE
      excretion parallels plasma levels and could reflect the general sympathoadrenal
      activity, whereas DA is primarily of renal origin. Renal DA and NE increase in
      the first 2 weeks of life in immature infants. We conclude that the catecholamine
      system of the human kidney undergoes maturational changes postnatally.

PMID- 9035173
TI  - Renal transplantation, chronic dialysis, and chronic renal insufficiency in
      children and adolescents. The 1995 Annual Report of the North American Pediatric
      Renal Transplant Cooperative Study.
AB  - The 1995 Annual Report of the North American Pediatric Renal Transplant
      Cooperative Study summarizes data voluntarily collected from 123 centers on 5,197
      children and adolescents grouped into three cohorts: (1) patients who received
      renal transplants on or after 1 January 1987 (n = 3,066), (2) patients who were
      maintained on peritoneal dialysis (PD) or hemodialysis (HD) on or after 1 January
      1992 (n = 1,488), and (3) patients treated for chronic renal insufficiency (CRI)
      on or after 1 January 1994 (n = 643). The transplant and dialysis information
      update previous registry data whereas the CRI information reflects 1st-year
      registry data. Three-year graft survival rates were 83% and 66% for living donor
      grafts and cadaver donor (CD) grafts, respectively. Triple drug maintenance
      therapy with prednisone, cyclosporine, and azathioprine was used by > 70% of all
      transplant recipients through 5 years of follow-up. The 2-year CD survival has
      steadily improved from 65% in 1987 to 82% in 1992. Fifty malignancies have been
      reported, the majority of which are lymphoproliferative disorders. The 2-year
      patient survival posttransplantation is 95%. Mortality rates for the youngest
      patients have drastically improved over the past 2 years. Approximately two
      thirds of patients in the dialysis cohort are maintained on PD; automated PD
      remains the preferred modality. Overall, the peritonitis rate is one infection
      every 13.3 patient months, the frequency of infection being greatest in the
      youngest patients. Whereas the primary reason for dialysis modality termination
      is transplantation approximately 40% of the entire dialysis cohort (PD at HD)
      were not considered active transplant candidate Baseline CRI data revealed the
      most common primary diagnoses to be obstructive uropathy (24%) and
      aplastic/hypoplastic/dysplastic kidneys (19%). The standardized height deficit in
      the CRI cohort was greatest in the younger patients and those with the most
      impaired renal function.

PMID- 9035174
TI  - Tertiary hyperparathyroidism after renal transplantation.
AB  - Tertiary hyperparathyroidism is considered as an autonomous proliferation state
      of the parathyroid glands with biological hyperfunction resistant to
      calcium/vitamin suppressor therapy. This phenomenon is thought to be secondary to
      monoclonal inactivation of tumoral growth suppression factor located on
      chromosome 11. Three patients, 13, 15, and 22 years of age, with chronic renal
      insufficiency of long evolution who presented with tertiary hyperparathyroidism
      following renal transplantation are described. The three patients underwent
      subtotal parathyroidectomy with consequent normalization of biochemical
      parameters of phospho-calcium metabolism in the first few weeks post surgery.
      Pathologic study showed adenoma in the affected glands with hyperplasia of the
      rest. We believe that in patients with long-term renal insufficiency an
      aggressive treatment, either medical or surgical, of secondary
      hyperparathyroidism which is continued after renal transplantation may be useful
      in preventing the development of tertiary hyperparathyroidism.

PMID- 9035175
TI  - Renal function in predialysis children with chronic renal failure treated with
      erythropoietin.
AB  - To assess the effect of long-term administration of human recombinant
      erythropoietin (EPO) on renal function, 11 anemic children aged 1.4-17.2 years
      were followed for 10-61 (mean 31) months on treatment. During EPO therapy the
      mean hemoglobin rose from 8.1 to 11.1 g/dl at the last observation. The final
      maintenance dose ranged between 70 and 300 U/kg per week. The rate of
      deterioration of renal function was calculated by comparing the slope of the
      regression lines of reciprocal serum creatinine values (SCr) derived from a mean
      of 20 values per patient obtained over 8-50 (mean 29) months before and a mean of
      24 SCR values during EPO therapy. The individual slopes improved after initiation
      of EPO therapy in all but 3 patients, but the mean change of slope (from -0.0521
      to -0.0299) was not significant. The study suggests that in most children with
      predialysis chronic renal failure long-term administration of EPO is not
      associated with accelerated deterioration but rather with delayed deterioration
      of renal function.

PMID- 9035176
TI  - Hemodialysis catheter survival and complications in children and adolescents.
AB  - Venous catheters have become an indispensable form of hemodialysis access. We
      evaluated catheter performance as temporary and long-term access in children with
      end-stage renal disease (ESRD). We assessed the survival rates and causes of
      catheter failure in 78 catheters used for hemodialysis access in 23 pediatric
      patients (aged 10 months to 22 years) with ESRD over a 5-year period. Median
      survival was 31 days for 56 uncuffed catheters. One- and 2-month actuarial
      survival was 69% and 48%, respectively. Reasons for removal were: elective (39%),
      kinking (36%), trauma (11%), infection (7%), and other (5%). Smaller catheters (7
      or 9 French) were more likely to be removed for kinking (P = 0.003). One-year
      actuarial survival for 22 cuffed catheters was 27%. Cuffed catheters were removed
      due to: infection (36%), kinking (14%), elective (9%), trauma (9%) and other
      (9%). Twelve catheters were removed for infection. Infection rates leading to
      removal were 0.58 and 0.71 per patient-year for uncuffed and cuffed catheters,
      respectively. Staphylococcus species were cultured most commonly. We conclude
      that uncuffed catheters function well for short-term hemodialysis access of up to
      2 months' duration and cuffed catheters are successful for long-term access in
      children and adolescents with ESRD.

PMID- 9035177
TI  - Two cases of nephrotic syndrome and tertian malaria in south-eastern Anatolia.
AB  - Tertian malaria is endemic in south-eastern Anatolia. As in Europe and America,
      in south-eastern Anatolia, an etiological agent is seldom identified in nephrotic
      syndrome. Two patients with Plasmodium vivax and nephrotic syndrome are described
      here. The possible relationship between Plasmodium vivax and nephrotic syndrome
      should be explored in children in endemic malarial regions.

PMID- 9035178
TI  - Anti-glomerular basement membrane nephritis in a 5-year-old girl.
AB  - We report a 5-year-old girl with anti-glomerular basement membrane nephritis. Her
      outcome was excellent with clearance of antibody and recovery of renal function 5
      weeks after the start of immunosuppression and plasmaphaeresis.

PMID- 9035179
TI  - Growth preservation after brief growth hormone therapy in chronic renal
      insufficiency.
AB  - A boy of 3 years 8 months with short stature due to chronic renal insufficiency
      was treated with recombinant human growth hormone (rhGH) for 20 months. Catch-up
      growth was achieved and the improvement of the height standard deviation score
      was sustained throughout an additional 4 years of follow-up without further rhGH
      therapy.

PMID- 9035180
TI  - Feeding dysfunction in infants with severe chronic renal failure after long-term
      nasogastric tube feeding.
AB  - Nasogastric tube feeding (NGTF) is frequently necessary to overcome the
      inadequate caloric intake of children with severe chronic renal failure (CRF). In
      a multicenter retrospective study, we evaluated feeding dysfunction after tube
      feeding withdrawal in children with severe CRF who started long-term enteral
      nutrition early in childhood. We considered, almost exclusively, infants who had
      started NGTF very early and continued to be tube fed for at least 9 months.
      Twelve patients were included in the study: 8 showed significant and persistent
      eating difficulties, with difficulties in chewing and swallowing in 7 and food
      refusal in 6. For 2 patients "panic attacks" from swallowing were repeatedly
      reported. These problems persisted for more than year in 5 patients and between 1
      and 6 months in 4. The possible feeding difficulties that may follow NTGF must be
      carefully evaluated. A possible means of overcoming these difficulties might
      include: encouraging the use of a pacifier, proposing water for spontaneous
      assumption, leaving the child the possibility of eating food spontaneously during
      the daytime, and increased support for the parents during weaning. These need
      prospective study.

PMID- 9035181
TI  - Vascular access for hemodialysis in children.
AB  - In the light of many years' experience in hemodialysis access surgery, the
      different methods of creating vascular access for dialysis treatment in the
      pediatric population are described. After presenting the various access types
      using autologous blood vessels and also heterologous grafts, their specific
      spectrum of complications is discussed in detail. Summarizing our experience it
      has to be emphasized that there is no specific angioaccess for children and
      adolescents, and that most vascular access procedures used in adults are also
      suitable for use in the young.

PMID- 9035182
TI  - C3 nephritic factor and mesangiocapillary glomerulonephritis.
AB  - The association of a C3 splitting activity, known as C3 nephritic factor (C3NeF),
      with mesangiocapillary glomerulonephritis (MCGN), especially MCGN type II, has
      long been known. Several forms of C3NeF are now recognised, the main one being an
      IgG which acts as an autoantibody binding to factor H, a normally occurring
      component of the complement system. Complement is in a continuous state of
      activation with inbuilt checks and controls, and factor H plays a very important
      part in the controlling mechanisms by preventing the overwhelming activation of
      complement at the stage of C3 conversion. C3NeF binds to factor H, thus
      preventing its inhibitory action, and allowing complement activation to proceed
      with, in vivo, the well-known consequences in MCGN of very low serum levels of
      C3. The question naturally arose whether C3NeF causes MCGN. Complex relationships
      between MCGN, C3NeF and partial lipodystrophy, also characterised by C3NeF and
      hypocomplementaemia, but preceding the development of MCGN, suggest that
      hypocomplementaemia predisposes to MCGN. Another possibility is that C3NeF acts
      directly within glomeruli to cause local complement activation and ensuing
      damage. Neither possibility could be resolved, but some recent observations have
      restimulated interest in a possible causative role for C3NeF in MCGN. First,
      factor H deficiency, by mechanisms other than blocking by C3NeF, in animals and
      man is associated with MCGN. Second, adipocytes, now known themselves to produce
      complement system proteins, are lysed in vitro by C3NeF, thus suggesting a
      mechanism for partial lipodystrophy. By analogy, the C3NeF may produce glomerular
      damage, as glomerular cells produce complement components.

PMID- 9035183
TI  - Atherosclerosis in youth: are hypertension and other coronary heart disease risk
      factors already at work?
AB  - The purposes of this review were to describe the natural history of
      atherosclerosis in youth, discuss the role of adult coronary heart disease (CHD)
      risk factors in the development of atherosclerosis-particularly in the young- and
      present the relationship between atherosclerosis and hypertension. Evidence is
      presented that, by age 15 years, 100% of the youth have aortic atherosclerosis
      and about one-half have coronary atherosclerosis. Risk factors for adult CHD,
      including lipoproteins, smoking, glycohemoglobin (a marker for diabetes),
      obesity, and hypertension, are associated with extent and prevalence of
      atherosclerosis in young people. Hypertension seems to play its role mainly by
      converting early atherosclerotic lesions (fatty streaks) to more advanced lesions
      (raised lesions).

PMID- 9035184
TI  - The evaluation of acute pyelonephritis and renal scarring with technetium 99m
      dimercaptosuccinic acid renal scintigraphy: evolving concepts and future
      directions.
AB  - Technetium 99m-dimercaptosuccinic acid (DMSA) scintigraphy has emerged as the
      imaging agent of choice for the detection and evaluation of acute pyelonephritis
      and renal cortical scarring in children. Consequently, DMSA scintigraphy provides
      a unique opportunity to study the progression of renal damage and functional loss
      from the initial insult of acute pyelonephritis to the subsequent development of
      irreversible renal scarring. Over the last few years, clinical and experimental
      investigations using DMSA renal scintigraphy have provided new insights into the
      etiology, pathophysiology, and clinical outcome of acute pyelonephritis in
      children. These studies have confirmed the primary role of the acute inflammatory
      response, associated with both reflux and nonreflux pyelonephritis, in the
      etiology of irreversible renal scarring. Furthermore, several studies have shown
      that renal scarring can be prevented or diminished by the early diagnosis and
      treatment of pyelonephritis. This review highlights these recent observations and
      makes recommendations regarding current clinical and future research
      applications.

PMID- 9035185
TI  - Clinical quiz. An infant with renal unresponsiveness.

PMID- 9035186
TI  - Lesch-Nyhan syndrome: clinical diagnosis and confirmation by biochemical and
      genetic methods.

PMID- 9035188
TI  - Community acquired Pseudomonas aeruginosa urinary tract infection in preschool
      children.

PMID- 9035187
TI  - Acute renal failure associated with amoxicillin and ibuprofen in an 11-year-old
      boy.

PMID- 9035189
TI  - Can intravenous cyclophosphamide be used for steroid-dependent nephrotic
      syndrome?

PMID- 9035190
TI  - Focal segmental glomerulosclerosis.

PMID- 9035191
TI  - Transplantation of a 14-year-old girl with nephronophthisis.

PMID- 9035192
TI  - Diagnosis and treatment of ILD.

PMID- 9035193
TI  - The diagnostic value of bronchoalveolar lavage in immunocompetent children with
      chronic diffuse pulmonary infiltrates.
AB  - We have investigated the diagnostic value of (BAL) in 29 immunocompetent children
      (ages 1 month to 18 years) with chronic diffuse pulmonary infiltrates on chest
      radiograph who presented for evaluation over a 3-year period. The median age at
      the time of the BAL was 20 months with a range of 1-210 months. Positive results
      (1) diagnostic of a primary disorder; (2) consistent with a diagnosis; or (3)
      diagnostic of a secondary disorder, were obtained in 20/29 patients (13 with a
      single positive BAL finding and 7 with more than one finding). BAL was diagnostic
      of a primary disorder in only 5 patients (17%) with aspiration detected in 3 and
      infection in 2. The differential diagnosis was narrowed in 15 patients by the
      presence of lymphocytosis, neutrophilia, or eosinophilia. A secondary disorder
      was uncovered in 8 patients. Negative results were obtained in 9 additional
      patients. We conclude that BAL provided useful information in children with
      chronic diffuse infiltrates, but its ability to determine the primary cause was
      limited.

PMID- 9035194
TI  - Childhood asthma and lung function in mid-adult life.
AB  - The longitudinal lung function data in 286 subjects from a 28 year follow-up of
      childhood asthma is reported. Airway obstruction in mid-adult life was present
      mainly in those with moderately severe asthma. Subjects who had been wheeze free
      for at least 3 years, even if asthma had been persistent in childhood, had normal
      lung function and no increased bronchial reactivity. Only two subjects, both with
      persistent asthma from childhood, failed to show an improvement in FEV1 of
      greater than 10% following inhalation of a beta-adrenergic agonist. Subjects with
      relatively mild asthma who had not taken inhaled steroids did not appear to be
      disadvantaged with respect to lung function.

PMID- 9035195
TI  - Chest surface mapping of lung sounds during methacholine challenge.
AB  - Wheeze as an indicator of airway obstruction during bronchoprovocation lacks
      sensitivity. We therefore studied whether induced airway narrowing is revealed by
      changes in normal (vesicular) lung sounds. Fifteen subjects with asthma and nine
      healthy controls, aged 8-16 years, performed a standardized methacholine
      challenge. Respiratory sounds were recorded with eight contact sensors, placed
      posteriorly over the right and left superior and basal lower lobes, and
      anteriorly over both upper lobes, the right middle lobe, and the trachea. Average
      spectra of normal inspiratory and expiratory sounds, excluding wheeze, were
      characterized in 12 asthmatics and 9 controls at flows of 1 +/- 0.2 L/sec. Airway
      narrowing was accompanied by significant changes in lung sounds, but not in
      tracheal sounds. Lung sounds showed a decrease in power at low frequencies during
      inspiration and an increase in power at high frequencies during expiration. These
      changes already occurred at a decrease in forced expiratory volume in 1 sec of
      less than 10% from baseline and were fully reversed after inhalation of
      salbutamol. Thus, lung sounds were sensitive to changes in airway caliber, but
      were not specific indicators of bronchial hyperresponsiveness.

PMID- 9035196
TI  - Pulmonary sequelae in infants treated with extracorporeal membrane oxygenation.
AB  - The decision to place an infant on extracorporeal membrane oxygenation (ECMO) is
      based on predictions of expected morbidity and mortality. One unknown factor is
      the relationship between pre-ECMO pulmonary dysfunction and on barotrauma and
      post-ECMO pulmonary sequelae. To determine whether placement of infants on
      extracorporeal membrane oxygenation (ECMO) early is associated with less
      subsequent pulmonary dysfunction than placing infants on EMCO later, we evaluated
      pulmonary function in 25 neonates prior to ECMO, when the infants had come off
      EMCO, and at the time of nursery discharge. Pulmonary resistance (R) and
      compliance (CL) were determined by a pneumotachograph and esophageal manometry,
      and functional residual capacity (FRC) was determined by a helium dilution
      method. Maximal expiratory flow (VmaxFRC) was determined by thoracic compression
      at the time of discharge. Infants were assigned to an early ECMO group (< 36
      hours of age, n = 12), or a late ECMO group (> 36 hours of age, n = 13). When
      first evaluated, the early group had a higher oxygenation index than the late
      group (mean value, 63 versus 48), but initial pulmonary function measurements
      were not different between the two groups. In the early group mean CL increase
      from 0.20 to 0.36 ml/cmH2O/kg, FRC increased from 7 to 20 ml/kg, and mean R
      decreased from 107 to 61 cmH2O/L/sec between the initial study and immediately
      after ECMO. In the late group, only FRC increased from a mean of 8 to 20 ml/kg.
      CL and FRC increased from post-ECMO to discharge in both groups (mean CL from
      0.36 to 0.76 ml/cmH2O/kg in the early group, and from 0.30 to 0.79 in the late
      group). Mean FRC increased from 20 to 26 ml/kg in the early group, and from 20 to
      25 ml/kg in the late group. VmaxFRC was lower in the late than the early group at
      discharge (mean, 1.14 versus 1.58 L/sec; P < 0.05). While both groups of infants
      had minimal pulmonary dysfunction at discharge, the infants placed on ECMO early
      had evidence of slightly less airway dysfunction despite a higher initial
      oxygenation index than the infants placed on ECMO late.

PMID- 9035197
TI  - Lung and heart-lung transplantation in children.

PMID- 9035198
TI  - Idiopathic pulmonary fibrosis in infants.
AB  - Idiopathic pulmonary fibrosis is a poorly characterized disease in infants. In
      the present report, we reviewed our experience with 10 infants during a 10-year
      period. In 9 patients, onset of symptoms occurred before the age of 2 months and
      included tachypnea, cough, and inadequate weight gain. However, despite the
      presence of these symptoms, diagnosis was delayed for 3 months at which time the
      infants were referred to the pediatric pulmonary department, when the diagnosis
      was confirmed by open lung biopsy. At the time of admission, bronchoscopy with
      alveolar lavage was performed in 9 children and showed severe alveolitis with an
      increase in the neutrophil count. Nine infants were treated with prednisone alone
      or in combination with chloroquine, colchicine, or cyclophosphamide; all these
      patients died despite treatment. One infant was treated with pulses of
      methylprednisolone because of a failure in response to oral prednisone. This girl
      who displayed similar clinical, radiological, and histological abnormalities as
      the other children at the time of diagnosis is the only child still alive after 3
      years of follow-up. She is now free of respiratory symptoms and has a normal
      growth curve. The present report raised two important points: (1) a thorough
      evaluation of characteristic symptoms should lead to an early diagnosis of
      pulmonary fibrosis in infants; and (2) administration of pulse therapy using
      corticosteroids has been helpful and needs to be evaluated further.

PMID- 9035200
TI  - Idiopathic bronchocentric granulomatosis in an adolescent.

PMID- 9035199
TI  - Familial interstitial lung disease in children: response to chloroquine treatment
      in one sibling with desquamative interstitial pneumonitis.
AB  - We describe a male infant with biopsy-confirmed interstitial lung disease (ILD)
      who responded to chloroquine, after he failed to improve on oral corticosteroids
      or cyclophosphamide. The infant presented at 8 days of age with respiratory
      distress and cyanosis. Lung biopsy at 8 weeks of age was consistent with
      desquamative interstitial pneumonitis (DIP). He was treated with corticosteroids
      at 2 weeks of age because of a family history of two siblings who died during
      infancy and who had DIP on postmortem examination. At 8.5 months, our patient was
      treated with cyclophosphamide because of lack of response to corticosteroids
      therapy. At 14 months of age, he began treatment with chloroquine in addition to
      corticosteroids and had a dramatic response within 3 weeks. The patient has been
      maintained successfully on continuous treatment with chloroquine alone for more
      than 9 years since this treatment was started.

PMID- 9035201
TI  - Hirschsprung's disease as a neurochristopathy.
AB  - Recent molecular-genetic and histochemical studies of intestinal aganglionosis
      have confirmed the initial classification established by Bolande, who considered
      Hirschsprung's disease (HD) a neurocristopathy. This paper is a critical review
      of the results of molecular-genetic studies carried out from 1992 to date. In
      particular, the author focuses on the possible clinical impact of the
      identification of RET as a causative gene for HD.

PMID- 9035203
TI  - Mutations of the endothelin-B receptor and endothelin-3 genes in Hirschsprung's
      disease.
AB  - The endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3) have
      recently been recognized as susceptibility genes for Hirschsprung's disease (HD).
      Novel EDNRB mutations have been detected in non-syndromic HD patients with
      heterozygous forms, and homozygous mutations of the EDNRB or the EDN3 genes have
      been reported in HD patients associated with type 2 Waardenburg syndrome. These
      observations confirm that impaired function of the endothelin-B receptor or
      endothelin-3 is involved in the aetiology of some human HD cases. EDNRB mutations
      appear to be associated with short-segment HD, in contrast to RET mutations,
      which are found mainly in long-segment aganglionosis.

PMID- 9035205
TI  - Prophylactic gastropexy in the asplenia syndrome.
AB  - The asplenia [Ivemark] syndrome (AS) is the association of congenital absence of
      the spleen with a variety of visceral abnormalities, predominantly of the
      cardiovascular system. Varying degrees of malrotation and malfixation of the
      bowel are common in this condition, and the occurrence of catastrophic gastric
      volvulus due to malfixation of the bowel has been reported. With the improvement
      in long-term outlook for these patients with modern cardiac surgery and
      prophylactic antibiotics, the intra-abdominal anomalies have become increasingly
      significant. This paper draws attention to the prophylactic treatment of gastric
      malfixation in the AS through the presentation of two cases in which gastropexy
      was performed.

PMID- 9035204
TI  - Metastasis of an intracranial germinoma through a ventriculoperitoneal shunt:
      recurrence as a yolk-sac tumor.
AB  - Extraneural metastases of intracranial germinomas, although infrequent, are
      associated with a generally poor prognosis despite the high radiosensitivity of
      localized primary tumors. Ventriculoperitoneal shunts have been implicated in
      facilitating metastatic spread of primary intracranial germinomas. We present a
      case of a successfully irradiated suprasellar germinoma recurring after 13 months
      as an intra-abdominal yolk-sac tumor in a young man. The tumor was eradicated
      with a combination of systemic chemotherapy and local irradiation, with no
      residual viable tumor cells confirmed at final surgical extirpation. The role of
      cerebrospinal fluid (CSF) shunts in metastases, mixed germ-cell tumor histology,
      and tumor markers in recurrences as well as radiation doses and volumes for
      treating primary tumors are discussed. Systemic chemotherapy may be utilized as
      prophylaxis against shunt metastases when CSF drainage is necessary.

PMID- 9035202
TI  - The RET proto-oncogene: a challenge to our understanding of disease pathogenesis.
AB  - RET gene alterations as disease-causative mutations have been demonstrated in
      five different disease entities: Hirschsprung's disease (HD); papillary thyroid
      carcinoma; and three types of inherited cancer syndromes: multiple endocrine
      neoplasia (MEN) 2A, MEN 2B, and familial medullary thyroid carcinoma. RET is
      expressed during embryogenesis in a temporally and spatially regulated manner,
      and plays an important role in the normal development of a variety of cell
      lineages, particularly in the establishment of the enteric nervous system. RET
      mutations observed in patients with HD are scattered along the gene without any
      hot spots, and possess a loss-of-function effect. RET mutations are detected with
      a higher incidence among familial cases (50%) than sporadic cases (15%-20%), and
      are more closely associated with long-segment HD than short-segment disease. In
      contrast to HD mutations, missense mutations observed in MEN 2 syndromes occur at
      specific codons, and gene rearrangements are characteristic in papillary thyroid
      carcinoma. Both missense mutations and gene rearrangements act in a dominant
      fashion, and cause constitutive phosphorylation on the tyrosine of RET and highly
      enhance RET kinase activity, leading to transforming or oncogenic activity.

PMID- 9035206
TI  - Comparison technetium of Tc-99m disofenin cholescintigraphy with ultrasonography
      in the differentiation of biliary atresia from other forms of neonatal jaundice.
AB  - Technetium Tc-99m disofenin cholescintigraphy (CS) and ultrasonography (US) are
      two major clinical methods used in differentiating biliary atresia (BA) from
      neonatal jaundice. To compare the diagnostic utility of these two modalities, 66
      patients with neonatal cholestasis (15 BA, 3 choledochal cyst (CC), 32 neonatal
      hepatitis, 13 prolonged jaundice, 2 total parenteral nutrition, and 1 sepsis)
      underwent Tc-99m disofenin CS and US. The diagnostic sensitivity, specificity,
      and accuracy of CS in differentiating BA from other forms of neonatal jaundice
      was 100%, 87.5%, and 90.5%, respectively, and for US 86.7%, 77.1%, and 79.4%,
      respectively. Tc-99m disofenin CS after premedication with phenobarbital and
      cholestyramine is a convenient and reliable method of differentiating BA from
      neonatal hepatitis, with a diagnostic accuracy superior to that of US. However,
      US is the initial imaging procedure of choice in patients presenting with
      jaundice to rule out anatomic anomalies such as CC.

PMID- 9035207
TI  - Small-bowel continuity: a crucial factor in determining survival in
      gastroschisis.
AB  - A retrospective analysis of a series of 63 cases of gastroschisis managed over an
      11-year period distinguished a single statistically significant prognostic
      factor. There were 6 (9.5%) deaths, of which 4 occurred in the 8 infants with
      small-bowel atresia/stenosis (P < 0.005, Fisher's exact test). One died at 48 h
      and the remaining 3 of liver disease related to total parenteral nutrition. Of
      the 4 survivors, 1 developed a late biliary stricture necessitating
      hepaticoenterostomy but is alive and well aged 4 years. The remaining 3,
      following initially prolonged hospitalisations and multiple operations, are alive
      and well after 2, 4 and 7 years. In 3 patients the atresia was not detected at
      the primary operation. The small number of cases of gastroschisis-associated
      small-bowel atresia seen in any one unit may conceal the importance of the
      problem, and limits experience in the approach to management.

PMID- 9035209
TI  - Ureteroceles in children: an ongoing challenge.
AB  - The treatment of ureteroceles in children requires an individualised approach.
      Antenatal diagnosis is the ideal, so that postnatal urinary antibiotic
      prophylaxis and appropriate investigations can be organised. Postnatal
      investigations should assess both upper and lower urinary tract. Renal and
      bladder ultrasound and radiographic micturating cystourethragraphy under
      antibiotic cover will both detect vesicoureteric reflux and assess any bladder
      outlet obstruction due to the ureterocele. Renal function, particularly of the
      upper moiety, is best evaluated by technetium Tc99m dimercaptosuccinic acid renal
      scan. Both function and obstruction can be quantitated by the Tc99m
      mercaptoacetyltriglycine isotope scan with intravenous volume expansion (10
      ml/kg) and furosemide diuresis (1 mg/kg). Intravenous urography provides the best
      anatomic information when the upper moiety is functional. The surgical management
      is based on the clinical situation, which is often variable, and therefore needs
      to be tailored for each patient. The general principles include restoration of
      anatomy to as near normal as possible and preservation of functional renal
      tissue.

PMID- 9035208
TI  - Detection of low-grade vesicoureteral reflux in children by color Doppler imaging
      mode.
AB  - Vesicoureteral reflux (VUR) is common in children with urinary tract infections
      (UTI) and may result in renal scarring or reflux nephropathy. To date, the
      primary diagnostic tool has been voiding cystourethrography (VCUG). A new
      technique for evaluation of grade 1 and 2 VUR is described using color Doppler
      imaging-mode cystography (CDIMC): 77 children, aged 7 months to 14 years, were
      examined for VUR by CDIMC and standard VCUG. According to the established reflux
      sonography (US) using a real-time mode, all patients selected for this study had
      a normal urinary tract on conventional gray-scale US. We studied 154 ureters, and
      a total of 31 were found to be refluxing on CDIMC and 30 on VCUG. A positive
      sonogram was defined as visualization of Doppler signals from the bladder to the
      ureter during the course of bladder filling. Taking VCUG as the gold standard, we
      had ten false-positive findings. The false-positive rate of 18.5% may have been
      due to the shorter observation time of fluoroscopy. Comparison of the two methods
      shows CDIMC to be 70% sensitive with a specificity of 92% in the detection of VUR
      grade 1 and 2. To evaluate the incidence of asymptomatic low-grade VUR in a non
      infected population, a second series of 38 children (19 males, 19 females) aged 3
      to 15 years (mean 8.8 years) with normal urologic status and urine cultures were
      studied by color Doppler imaging mode (CDIM) for detection of asymptomatic low
      grade VUR. Four children were found to have a unilateral refluxing ureter. The
      incidence of VUR in children with a normal urinary tract and no prior UTI was
      10.5%. In conclusion, CDIMC can be used as a possible alternative to standard
      VCUG for the screening and follow-up of low-grade VUR. In addition, our study
      indicates that asymptomatic grade 1 and 2 reflux might be a physiological
      condition.

PMID- 9035210
TI  - An in vitro study of silicone migration from intravenous fluid tubing.
AB  - Migration of particulate matter from plastic tubing and solid plastic implants
      has been documented in a number of studies, including some with the use of
      cardiac bypass, haemodialysis, and pump-assisted intravenous infusions. In order
      to ascertain whether silicone embolisation occurs when children have an Ivac 560
      pump-assisted IV infusion, we passed 180 ml of pumped fluid through a microfilter
      and compared the scanning electron micrographs of those filters with unused
      filters and with others through which a similar volume had been passed without
      using the pump. The particles on the filters were analysed for their elemental
      content using energy-dispersive X-ray analysis. In addition, the appearance of
      the silicone tubing used in the pump over 3 and 72 h was assessed and compared to
      that of flow-only and unused tubing. More particles were found on the microfilter
      when fluid had been delivered via the pump than on those through which non-pumped
      fluid had passed or that were unused. Elemental silicon-containing particles were
      only found on the filter when a pump had been attached to the IV line. The flow
      only and unused tubing were found to have adherent particles on the inner surface
      that were not seen once the tubing had been used for 3 h in the Ivac 560 pump.
      Also, after 72 h use, the silicone tubing had a deformed inner layer. The
      clinical significance of these findings is yet to be determined, but it does
      appear that silicone embolisation occurs during pump-assisted infusions in
      children.

PMID- 9035212
TI  - Necrotizing enterocolitis in a term infant with coarctation of the aorta complex.
AB  - Necrotizing enterocolitis (NEC) sometimes occurs in term infants with congenital
      heart disease. This article reports a rare case of a term infant with coarctation
      of the aorta complex who developed NEC on the 8th day after birth. Spontaneous
      closure of the ductus arteriosus in the 1st week of life may cause intestinal
      ischemia and hypoxia with resultant NEC.

PMID- 9035211
TI  - Accessory hepatic duct associated with a choledochal cyst.
AB  - This case report describes an accessory hepatic duct (AHD) identified by
      intraoperative cholangiography during excisional surgery of a choledochal cyst
      (CC). The accessory duct was divided and reconstructed successfully to the Roux
      en-Y jejunal loop. The postoperative course was uneventful, and follow-up
      abdominal sonography revealed neither evidence of biliary tract obstruction nor
      atrophic changes of the liver. It is advocated that an AHD should be meticulously
      reconstructed if it is divided during excisional surgery of a CC.

PMID- 9035213
TI  - Delayed presentation of a right-sided diaphragmatic hernia following necrotizing
      enterocolitis: case report.
AB  - We report a case of a right-sided diaphragmatic hernia in a premature twin, which
      presented in the 2nd week of life with a persistent pleural effusion following a
      bowel perforation due to necrotizing enterocolitis. The position of the right
      hemidiaphragm initially was normal and the definite diagnosis was made by
      ultrasound.

PMID- 9035214
TI  - Incarcerated umbilical hernia in children.
AB  - Over a period of 5 years, four cases of incarcerated (one strangulated) umbilical
      hernia (UH) in children were observed and treated in Saint-Denis, France. In a
      review of the literature, only 45 descriptions of complicated UHs in children
      were found worldwide. Incarceration of UHs is considered to be very rare in
      children, however, it appears to occur more frequently than it is generally
      believed. Therefore, a more active therapeutic approach is recommended even in
      smaller hernias, from more than an aesthetic point of view.

PMID- 9035215
TI  - Agenesis of the urinary bladder with cutaneous ectopic ureteric orifice and
      multiple birth defects.
AB  - This is to our knowledge the first case in the world literature of a liveborn
      baby with a tubular colonic duplication, agenesis of the urinary bladder,
      urethral atresia, and a single pelvic kidney with its ureter opening directly
      onto the skin in the region of the natal cleft. A brief review of the embryology
      is included and an attempt is made to explain the embryologic basis for this
      anomaly.

PMID- 9035216
TI  - Ectopic neural tissue as an unusual cause of a retroperitoneal tumor.
AB  - In a 3-year-old boy an abdominal mass was palpated by chance, which consisted of
      cystic and solid structures and was shown on ultrasound scan and computed
      tomography to be located retroperitoneally. Intraoperatively, the cystic tumor
      contained clear, yellowish fluid and had a stalk leading to the interspinal space
      between L2 and L3. However, no signs of dysraphism, were found. Neuropathologic
      examination surprisingly showed non-neoplastic ectopic neural tissue, which has
      never been recorded at this extraspinal site before.

PMID- 9035217
TI  - Congenital retroperitoneal tumour: rhabdomyoma or rhabdomyosarcoma?
AB  - This case report demonstrates the difficulties experienced by pathologists when
      confronted with a tumour that is not typical of either a benign tumour or its
      malignant counterpart and adds to the rapidly growing list of conditions
      diagnosed by means of antenatal ultrasonography.

PMID- 9035218
TI  - Lipoblastomatosis in a newborn: case report.
AB  - A male newborn had a well-circumscribed, solid mass on the right anterior chest
      wall at birth. Computed tomography disclosed an infiltrating soft-tissue mass
      over the right 6th to 9th ribs near the costochondral junction. Surgical excision
      was done at the age of 5 days. Pathologic examination showed lipoblastomatosis.

PMID- 9035219
TI  - Continuous extracorporeal stool-transport system: a new and economical procedure
      for transitory short-bowel syndrome in prematures and newborns.
AB  - Between May 1994 and June 1995, nine newborns underwent surgery due to mechanical
      ileus or intrauterine perforation of the small bowel. Three were very-low-birth
      weight infants weighing between 520 and 1,200 g. Surgery was performed in the
      first 2 days of life and split ileo- or jejunostomas were implanted. Early oral
      nutrition was initiated. To avoid non-use of the distal bowel and short-bowel
      syndrome, the aboral stoma was irrigated a few days later with the proximal
      feces. A new technique was applied to transport the chyle continuously from the
      oral to the aboral stoma: the stool was collected in an especially constructed
      stoma bag and transported distally by a roller pump. No major complications were
      seen. The general outcome was excellent in all cases, and reanastomosis under
      optimal bowel conditions was achieved in all patients without further problems.

PMID- 9035220
TI  - A new instrument for suction rectal biopsy in the diagnosis of Hirschsprung's
      disease.
AB  - A new instrument for suction rectal biopsy in infants suspected of having
      Hirschsprung's disease is described that can be completely dismantled, physically
      cleaned, lubricated, and heat-sterilised. These attributes are new and are
      absolutely critical today. The instrument has been used in 60 patients (ca. 180
      biopsies) from 1988 to 1994. A successful biopsy was usually achieved and no
      major complications occurred. Recently, a second biopsy capsule with a larger
      port has been added, thus enhancing the versatility of the instrument. The
      original instrument has never been sharpened or repaired and is still in use. A
      direct descendant of this prototype instrument is now commercially available.

PMID- 9035221
TI  - Phase IV research and drug utilization observation studies.

PMID- 9035222
TI  - Post-approval drug research: objectives and methods.
AB  - The limitations of pre-marketing clinical trials are analyzed and the need for
      ongoing drug research after approval is emphasized. Rare adverse drug reactions
      constitute the most important but not the only question. In addition to so-called
      post-marketing Drug Utilization Observation studies and spontaneous event
      reporting systems, other pharmacoepidemiologic study approaches like comparative
      cohort studies and case control studies, and also randomized clinical trials, are
      necessary to meet the multitude of scientific objectives of post-approval drug
      research.

PMID- 9035223
TI  - The treatment of depression with paroxetine in psychiatric practice in Germany:
      the possibilities and current limitations of drug monitoring.
AB  - A drug monitoring of the antidepressant paroxetine was carried out in Germany
      from August 1992 to November 1993. The principal aim of this study was to collect
      demographic, diagnostic, efficacy, and medical-safety data regarding patients who
      were treated for up to 12 weeks with this SSRI. A secondary goal was the
      investigation of differences between patients who left treatment after 6 weeks or
      earlier and those who continued treatment. Evaluable data were obtained from 507
      psychiatrists for 2817 patients, 1301 of whom extended treatment beyond 6 weeks.
      64% of the patients had been pretreated for the current episode of depression.
      50% were considered by their doctors to have either chronic or recurrent illness
      and 92% to possess moderate to severe symptomatology. Concomitant psychotropic
      medication was reported in 43% of cases, the most frequent medications being
      benzodiazepines, neuroleptics, and/or tricyclic antidepressants. Clear or
      complete improvement was noted for 63% of assessable patients by the end of week
      6 and for 79% of the patients who extended treatment to 12 weeks. There were
      significantly more patients with DSM major depression and severe symptoms in the
      treatment-extender than in the 6-week treatment group. Paroxetine was tolerated
      well by most patients: of the 1009 adverse events reported, only 17 were
      considered "serious". There were no suicides or cases of overdose attributable to
      paroxetine. The discussion of these results is the basis for a critical appraisal
      of postmarketing-surveillance methodology. It is concluded that, despite its
      present structural weaknesses as compared to controlled investigations, drug
      monitoring of a new medication in the immediate postmarketing period can give
      insights into the treatment of large numbers of patients under private-practice
      conditions. However, drug monitoring as it is conducted in Germany can have
      different and perhaps conflicting functions which may limit its effectiveness.
      The authors recommend that all interested parties (physicians, the pharmaceutical
      industry, regulatory bodies) engage in a continuous dialog aimed at clearly
      formulating the goals and improving the methodology of drug monitoring.

PMID- 9035224
TI  - Quality-monitoring of psychotropic drug therapy in post-marketing surveillance.
      Results of a drug utilization observation (DUO) study on moclobemide.
AB  - Thanks to their non-intervening nature, post-marketing drug utilization
      observation (DUO) studies reflect both the properties of the substance under
      investigation and doctors' treatment decisions, thus-in contrast with clinical
      trials-allowing the interactions of these two factors to be investigated. A DUO
      study involving the administration of moclobemide to 9419 patients investigated
      the prescribing behavior of about two-thirds of all general practitioners and
      internists in Germany prescribing moclobemide during the study period. The
      results obtained suggest that, on the whole, moclobemide is being prescribed
      knowledgeably and correctly for the treatment of the full spectrum of depressive
      disorders. The management of these patients tended to adhere strictly to existing
      treatment recommendations while at the same time revealing a certain degree of
      latitude for treatment optimization. This applies particularly to the utilization
      of the recommended dosage range, especially in severely depressed states, and the
      consistent, syndrome-based combination treatment with hypnotics/sedatives or
      neuroleptics in the respective patient groups indicated. Potential interactions
      though comparatively few are known for moclobemide-were taken into account in
      most cases. The safety profile closely matches the experience gained from
      clinical trials. Despite the large sample size involved there was no evidence of
      any hitherto unknown serious events. The experience gained during this survey
      suggests that the DUO study is a suitable instrument for monitoring the use of an
      antidepressant in the early post-registration period, enabling action to be taken
      at an early stage to correct any systematic deviations from the conditions of
      registration.

PMID- 9035225
TI  - Antidepressant drug use: differences between psychiatrists and general
      practitioners. Results from a drug utilization observation study with fluoxetine.
AB  - Between 1990 and 1993, a series of drug utilization observation studies with
      fluoxetine (Flx) were conducted in Germany in several waves. 3,158 patients
      treated by psychiatrists/neurologists (PN) and 15,601 patients treated by general
      practitioners/internists (GPI) were included; data collection at start and end of
      treatment focussed on diagnoses, symptoms, prescription, comedication, efficacy
      (CGI, Zung scale), and adverse events. Differences between PN and GPI patients
      were of major interest. For more than 90% of both the PN and the GPI cases. Fix
      was used for the indication of "depression", with a dosis of 20 mg/day. More PN
      patients (47%) than GPI patients (28%) were diagnosed as "endogenous"; GPI
      patients more often presented with first episodes (36 vs. 24%). "suicidal
      ideation" was less prominent compared to PN subjects (17 vs. 28%). Psychotropic
      comedication was regarded as necessary in 39% (PN) and 10% (GPI) of the cases.
      Early treatment termination because of "remission/major improvement" was observed
      in 13% (PN) vs. 21% (GPI) and because of "adverse events" in 11% (PN) vs. 3%
      (GPI) of the patients. At observation end, 53% (PN) vs. 74% (GPI) were rated as
      "symptom-free/markedly improved" (CGI); self-ratings reflected comparable
      results, marked improvements over time, but still PN/GPI differences at the end.
      "Suicidality" related to depression was more pronounced in the PN group at both
      points in time. 24% (PN) vs. 6% (GPI) of the cases reported "routine" adverse
      events, while in 2% (PN) and 1% (GPI) "serious" adverse events were observed.
      (For all the above comparisons p < 0.001 to < 0.0001.) These findings reveal that
      under routine conditions handled by PNs and GPIs-Fix shows an efficacy and safety
      consistent with clinical trial data. The body of data suggests that PN patients
      present with more severe depression and more suicidality, require more
      comedication, and end up with a poorer outcome. Differences in the physicians'
      perception of psychiatric and somatic symptomatology and their treatment routines
      may also have something to do with the PN/GPI group differences observed.

PMID- 9035226
TI  - What happens to patients after the end of a clinical trial? Systematic follow-up
      observational study of an open moclobemide trial in major depression.
AB  - Controlled clinical drug trials typically last several weeks. At the end of this
      fixed time period approximately two-thirds of the patients in trials with
      antidepressant drugs are classified as responders, i.e. the initial severity
      score is reduced by about fifty percent. In a clinical perspective this means
      that many patients, even among the responders, are still quite ill and require
      further treatment. Nevertheless, to date there do not appear to have been any
      studies on treatment and course of illness after the termination of controlled
      clinical trials. In a "naturalistic" follow-up surveillance study of 202 patients
      who had taken part in a controlled trial with the antidepressant moclobemide for
      six weeks, treatment and clinical status were monitored through questionnaires
      sent out to their treating physicians (n = 78) at two assessment points four
      weeks and six months later. Results showed that sixty percent of patients
      continued to receive the study drug moclobemide after the completion of the
      clinical trial. Twenty percent were switched to other antidepressants and twelve
      percent received no further psychotropic drugs. In the course of six months a
      considerable variation in treatment modes could be observed. Patients under
      ongoing active treatment made considerable additional progress. A correlation was
      found between insufficient response and repeated switching of medication.
      Patients who had been taken off antidepressant medication because of early good
      response did not experience early relapse after the end of treatment.

PMID- 9035227
TI  - An investigation of the representativity of neuropsychiatrists and their patients
      in a drug utilization observation study on fluoxetine.
AB  - This study presents a methodological approach to an expost facto investigation of
      sample bias in drug utilization observation (DUO) studies using the example of a
      DUO with the nontricyclic antidepressant fluoxetine. A total of 479 psychiatrists
      and neurologists and 2,401 patients were investigated. The purpose of the study
      was to judge the representativeness of our DUO sample for two populations: first,
      for all psychiatrics and neurologists prescribing fluoxetine or all patients
      being treated with fluoxetine in Germany and, second, for all psychiatrists and
      neurologists prescribing antidepressants or all patients being treated with
      antidepressants in Germany. Criteria for the representativeness test were
      physician variables (gender, size of community where practicing, federal state,
      age, volume of prescriptions) and patient variables (gender, age, prescription
      related diagnosis, concurrent illnesses, concomitant medications). The study
      shows that the DUO sample can rightfully claim representativeness in the majority
      of parameters for the psychiatrists and neurologists prescribing fluoxetine and
      for the patients being treated with fluoxetine. There are more noticeable
      discrepancies with regard to the psychiatrists and neurologists in general and to
      the patients being treated with antidepressants in general. The methodological
      problems of pharmacoepidemiological investigation of representativeness are
      discussed.

PMID- 9035228
TI  - Drug monitoring studies as a method of analyzing response criteria.
AB  - Two multicenter drug monitoring studies are presented. Some methodological
      problems are dealt with and the validity of such studies is discussed in terms of
      differential indication. In a first study (Lehmann et al., 1993) the results of a
      12-week xanthinol niacinate treatment (500 to 3000 mg daily) in a cohort of
      10,134 outpatients suffering from cerebrovascular insufficiencies were recorded
      systematically by nonreactive evaluation methods. The therapy was found to be
      most successful in patients with the target symptoms vertigo, tiredness, lack of
      concentration, affective disorder, and disturbances of vigilance and vitality.
      The most frequent side-effects were flush or heat sensations in 9.1% of the
      patients and gastrointestinal complaints in 3.3%. In a second study (Klieser et
      al., 1994) we systematically collected data from 219 patients with Major
      Depressive Disorder during five weeks of treatment with fluoxetine (20 mg daily).
      The results showed that depressively inhibited, anxious patients with a
      depression of minor severity, who showed a relatively marked improvement within
      the first week of treatment, profited the most from this therapy. The first study
      was designed to use nonreactive evaluation methods. Correlation analyses helped
      to identify the types of patient with a good response to treatment. The second
      study was organized on the model of conventional controlled pharmacological
      studies with the application of commonly used scales. The differential indication
      was to be inferred from the uni- and multivariate comparison of responders and
      nonresponders. In the light of these two studies, the problems of target
      definition, sample design, target variables, practicability, statistical
      analysis, and validity are discussed.

PMID- 9035229
TI  - Mortality studies and the effectiveness of drugs in long-term treatment.
AB  - In scientific observations on the utilization of drugs under routine treatment
      conditions in patients with affective disorders, one of the main problems is the
      establishment of criteria for measuring treatment effectiveness. As the mortality
      risk of such patients is considerable, the mortality rate is an important outcome
      criterion for determining the long-term effectiveness of medication administered
      in routine treatment settings. Mortality studies are typical phase IV studies;
      the researcher does not interact with the treatment procedure, he only observes
      the results of treatment with respect to death rates. As lithium treatment is of
      increasing importance and interest as a major prophylactic agent in recurrent
      affective disorders and is by its nature a long-term treatment, such a therapy
      provides an excellent field for observations of effectiveness under long-term
      treatment conditions. Mortality studies can take into account various factors,
      such as type of treatment setting, treatment regimen, drop-out analysis, and
      comparison between times on and off treatment. Results from several mortality
      studies on lithium-treated patients are reported in order to demonstrate the
      methodology and outcome of long-term observation of drug treatment. Mortality
      studies conducted within the framework of phase IV studies and particularly
      within the concept of pharmacoeconomics can help to demonstrate the effectiveness
      of long-term treatment, and are an important methodological adjunct to controlled
      clinical trials.

PMID- 9035230
TI  - International guidelines on post-authorisation research and surveillance.
      European Economic Community.
AB  - Recently, post authorisation research and surveillance has become more and more
      important. This article investigates which common standards already exist and
      which methods and tools are used in this context. This paper focusses on a draft
      version of the "Notice to applicants for marketing authorisations for medical
      products for human use in the European Community" which will be mandatory for all
      EC member countries after its finalization.

PMID- 9035231
TI  - Guidelines for the implementation of drug utilization observation (DUO) studies
      in psychopharmacological therapy. The "Phase IV Research" Task-Force of the
      Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP).
AB  - The task-force on Phase-IV-Research of the Association for Neuropharmacology and
      Pharmacopsychiatry (AGNP) has developed guidelines for the implementation of
      scientifically sound drug utilisation observation studies (DUO studies). These
      guidelines have been adopted by the executive committee as the position of the
      association. DUO studies are prospective pharmacoepidemiological studies, by
      which prescription, illness, and patient data of individual patients are
      collected without interference with the routine course of treatment. They can
      answer questions on the interaction of treatment modalities with positive and
      negative treatment outcome. Scientific standards require that there is a study
      protocol which describes the epidemiological, statistical, procedural, and
      quality assurance methodology and states who is responsible for what. As such
      studies can violate data protection regulations or can be used for sales instead
      of scientific purposes, consultation of an ethics committee is recommended.

PMID- 9035232
TI  - A novel synthesis of 1,2,4-triazolo[1,5-a]isoindolinetrione, 1,2,4-triazolo[1,5
      a]pyrimidine and 1,2,4-triazolo[2,3-a]quinazolinedione derivatives and their
      antibacterial activity.

PMID- 9035233
TI  - Bacterial adhesins as a drug carrier: covalent attachment of K99 fimbriae to 6
      methylprednisolone.
AB  - A bioadhesive drug delivery system based on the covalent attachment of a
      therapeutic agent to bacterial fimbriae is described. This approach involves the
      isolation of the fimbrium K99 as well as the covalent coupling of 6
      methylprednisolone to this adhesin via a linker, especially designed to be
      cleaved by unspecific luminal esterases. Analysis of the conjugate showed a
      direct correlation between solubility and coupling extent. Under physiological
      conditions, a conjugate exhibiting a coupling extent higher than 0.8 (mol
      therapeutic agent/mol fimbrial subunit) demonstrated a dramatically decrease of
      solubility. Release of the drug could be verified by enzymatic cleavage of the
      conjugate in vitro. The adhesive properties of a drug delivery system containing
      6-methylprednisolone and K99 fimbriae were assayed by a haemagglutination test.

PMID- 9035235
TI  - Effect of oil phase composition on the skin permeation of felodipine from o/w
      microemulsions.
AB  - Oil/water microemulsions containing benzyl alcohol or different ratios of benzyl
      alcohol and isopropyl myristate as oil phase were prepared and used as vehicles
      for the transdermal absorption of felodipine. Skin permeation from the
      microemulsions was compared with that from a drug suspension in an apparent
      external phase of a microemulsion and with an aqueous drug suspension. The
      highest flux was from the microemulsion with the highest solubility of
      felodipine, while the permeation rate decreased over time from the suspension in
      the apparent external phase. The flux from the aqueous suspension was 10-50 times
      lower than that from the microemulsions. These results indicate that
      microemulsions containing benzyl alcohol may be interesting vehicles for
      transdermal administration of felodipine.

PMID- 9035234
TI  - Characterization of a commercial liposome spray.
AB  - The commercial liposome spray Heparin-pur-ratiopharm was physicochemically
      characterized. This preparation is said to result in a fine gel-film containing
      pure, concentrated liposomes (including drug) on the skin after application and
      evaporation of the water/ethanol-mixture of the system. As phospholipids tends to
      form lamellar structures at lower water concentrations the structural
      characteristics of Heparin-pur-ratiopharm were investigated in the original
      preparation and after a drying process, which should be comparable to application
      on skin. For the characterization several methods were used, e.g. photon
      correlation spectroscopy, electron and polarized light microscopy, small angle X
      ray (SAX) scattering and SAX diffraction. The results of the present
      investigation indicate that there are no changes in the colloidal state of the
      phospholipids before and after drying and application of the spray. There seem to
      be only changes in the degree of dispersion of the liquid crystalline phase, i.e.
      from small uni- or oligolamellar liposomes in the original preparation via
      multilamellar vesicles to a lamellar mesophase during the drying process.
      Therefore, it seems that there are no differences for the application of heparin
      if a preparation containing small uni- or oligolamellar liposomes is used or if
      the phospholipids are structured differently. The major point of importance for
      drug application, therefore, seems to be the presence of phospholipids as they
      possibly work as enhancer for the uptake of the drug through the skin to achieve
      a quick effect.

PMID- 9035236
TI  - Polycyclic aromatic alkaloids. XII: In vitro- and in vivo-investigations of the
      cytotoxic marine alkaloid 2-bromoleptoclinidinone.
AB  - Aminoquinone 2a, the tetracyclic quinone 3b, and the pentacyclic alkaloid 2
      bromoleptoclinidinone (4a) were submitted to the NCl standard in vitro assay
      using 60 tumor cell lines. Compound 4a showed very high in vitro cytotoxicity and
      was therefore selected for further evaluation. In the in vivo screening 4a was
      tested at maximally tolerated doses in four models, but no significant antitumor
      activity could be found.

PMID- 9035237
TI  - Antioxidant activities of polyphenolic extracts from flowers, in vitro callus and
      cell suspension cultures of Crataegus monogyna.
AB  - Numerous plants synthesize among their secondary metabolites phenolic compounds
      which possess antioxidant effects. The aim of the present work was to assay the
      antioxidant activities of phenolics from Crataegus monogyna Jacq. flowers and in
      vitro tissue culture (calli and cell suspensions) extracts. In the case of tissue
      culture extracts, the phenolic production is studied at three different stages of
      one subculture period (initial growth period, increasing and maximal phenolic
      synthesis phases). Attention was paid to the main categories: flavonoids and
      proanthocyanidins, and to the principal individual components. Total phenolic
      amounts decrease in the order: fresh flowers > cell suspension cultures > callus
      cultures. The antioxidant activities of these different extracts against H2O2 and
      HOCl, have been determined in vitro. All the extracts are efficient and the
      scavenging capacity is clearly related to the total phenol content. The
      scavenging effects of the cell suspension extracts are similar to those of the
      flowers. Among individual compounds, the flavanol-type derivatives, specially the
      proanthocyanidin B2, are more efficient. Thus, in vitro plant tissues could be an
      interesting source of bioactive molecules.

PMID- 9035238
TI  - Synthesis and CNS activity of 1-alkyl-5-arylimidazolidine-2-thiones.

PMID- 9035239
TI  - Biological activities of buddlejasaponin isolated from Buddleja madagascariensis
      and Scrophularia scorodonia.

PMID- 9035241
TI  - Food deprivation and food-delay effects on the development of adjunctive
      drinking.
AB  - Twelve rats were food-deprived to 90% or 70% of their free-feeding weights. Food
      pellets were then delivered every 60 s (Fixed Time 60-s schedule), and the
      development of adjunctive drinking was measured by the water consumed and the
      number of licks. For "master" rats, each lick was followed by 10-s delays in food
      delivery. Yoked control rats received food at the same time as their master rats
      and independently of their own behavior. At 70% deprivation, both master and
      control rats developed similar levels of schedule-induced licking, but the master
      rats drank less water. At 90% deprivation, master animals showed little drinking
      and licking, but the development of adjunctive drinking was not completely
      prevented. Drinking by yoked control rats did not differ as a function of
      deprivation level. In showing that lick-dependent delays in food delivery reduce
      the asymptotic development of adjunctive drinking as a function of the rats'
      level of food deprivation, these results support the view that environmental
      influences on schedule-induced drinking are modulated by motivational factors.

PMID- 9035240
TI  - A new flavone glycoside with antimicrobial activity from Carduus pycnocephalus L.

PMID- 9035242
TI  - Absolute and spectral sensitivities in dark- and light-adapted Pagothenia
      borchgrevinki, an Antarctic nototheniid fish.
AB  - Functional properties of the retina of Pagothenia borchgrevinki, an Antarctic
      nototheniid fish that lives beneath the 2.5-3 m thick sea-ice in water of -1.8
      degrees C temperature, were analyzed electrophysiologically at Scott Base (77
      degrees 50'S; 166 degrees 45'E). The waveform of the ERG was monophasic in the
      dark-adapted state and showed an off-response of opposite polarity in the light
      adapted condition. Responses of the light-adapted retina were smaller than those
      of the dark-adapted eye, although both photopic and scotopic components were
      observed. Spectral sensitivity measured by monochromatic photostimulation at 14
      different wavelengths across the 400-700-nm range showed a single maximum at 490
      nm. The spectral sensitivity curve is consistent with a rhodopsin photopigment.
      The dark-adapted retina exhibited a photon flux density threshold of
      approximately 2 x 10(9) photons cm-2 s-1) when monochromatic flashes of 500 nm
      wavelength and 250 ms duration were used. When the stimulus consisted of 1 s
      white light, a minimum energy flux density of approx. 2 x 10(-4) microW/cm2 was
      necessary to elicit a detectable response. It was concluded that the visual
      system of P. borchgrevinki was in tune with the dominant downwelling spectral
      irradiance and that, due to retinal thermal noise reduction in the cold
      environment, no great need for particular anatomical adaptations to further
      enhance sensitivity existed.

PMID- 9035243
TI  - Effects of p-chlorophenylalanine on reflexive and noncontact penile erections in
      male rats.
AB  - To clarify the role of serotonin in penile erection, testosterone-primed
      castrated male rats were treated with the serotonin-synthesis inhibitor, p
      chlorophenylalanine (pCPA), and reflexive erection (RE; male supine, penile
      sheath retracted) and noncontact erection (NCE; penile erection evoked by remote
      sexual stimuli) tests were performed. Half the males were injected with 100 mg/kg
      pCPA 4 times before each test; control males were treated with saline instead of
      pCPA. In the RE test, compared to the control group, pCPA-treated males had a
      shorter erection latency, but they also displayed fewer erections. NCE tests were
      conducted as a 2 x 2 factorial experiment: pCPA or saline, and estrous female
      present or absent. Only the pCPA-female Group had a high proportion of responders
      (68%), compared to 14-27% in the other Groups (p < 0.02). These results suggest
      that the serotonergic system exerts facilitative and inhibitory influences on
      different systems in regulating reflexive erection. On the other hand, serotonin
      appears to play an inhibitory role in the induction of noncontact erection,
      because pCPA did not directly induce erection, but rather facilitated the
      response to females.

PMID- 9035244
TI  - Effect of glucose and 2-deoxyglucose on hypothalamic GABA release in lactating
      rats.
AB  - Gamma-amino butyric acid (GABA), an inhibitory neurotransmitter, has been
      implicated in the control of feeding behavior. This study was conducted to
      investigate the in vitro release of GABA in the basal medial hypothalamus (BMH)
      of hyperphagic lactating (L) and control nonlactating (NL) rats. Pregnant Sprague
      Dawley rats (n = 10) were ad lib fed a semipurified powdered diet during the last
      6 days of pregnancy until day 19 of lactation. Nonpregnant (n = 10) animals
      served as controls. Body weights and food intake were recorded every other day.
      Lactating rats demonstrated an increase in body weight as well as food intake as
      compared to nonlactating animals. At sacrifice, the BMH was removed and perfused
      (0.1 ml/min) with Kreb's Ringer buffer (KRB) ("basal" medium) using a Brandel
      perifusion system. KRB containing glucose (100 mM) or 2-deoxyglucose (2DG) (100
      mM) was also applied to the tissue. Potassium stimulation was carried out to test
      for the viability of the tissues. Samples were collected every 10 min,
      derivatized with O-Phthalaldehyde and analyzed via HPLC. Glucose depressed, and
      2DG enhanced GABA release compared to basal levels. There were no significant
      differences in GABA release between lactating and nonlactating groups. These data
      suggest that GABA release is responsive to metabolic changes in the brain.

PMID- 9035245
TI  - Postexercise thermoregulatory behavior and recovery from exercise in desert
      iguanas.
AB  - Desert iguanas (Dipsosaurus dorsalis) undergo respiratory recovery more rapidly
      and incur lower energetic costs when they recover from 40 degrees C burst
      activity at 20 degrees C than when they recover at 40 degrees C. However, a body
      temperature of 20 degrees C falls well outside the preferred activity temperature
      range of this species, and imposes several physiological and behavioral
      liabilities. To determine if exhausted animals would favor a thermal regimen that
      allows for rapid and inexpensive respiratory recovery, we exercised lizards to
      exhaustion and allowed them to recover in a laboratory thermal gradient for 180
      min. Recovering animals allowed their body temperatures to cool significantly to
      a mean temperature of 33.5 degrees C during the first 60 min of recovery, and
      subsequently rewarmed themselves to an average temperature of 38 degrees C for
      the remainder of their recovery period. Control animals maintained a constant
      body temperature of 37.7 degrees C throughout the 180-min recovery period. We
      then exercised animals to exhaustion at 40 degrees C and allowed them to recover
      for 180 min under a thermal regimen that mimicked that selected by exhausted
      animals in the previous experiment. Animals recovering under this thermal regimen
      returned to rates of O2 consumption, removed exercise-generated blood lactate,
      and incurred energetic costs that were more similar to data previously collected
      for animals recovering from exercise at a constant 40 degrees C than to data from
      animals recovering at 20 degrees C. These results suggested that the energetic
      benefits associated with recovery at 20 degrees C are not of sufficient
      biological importance to cause a major shift in thermoregulatory behavior.

PMID- 9035246
TI  - Adaptation to capsaicin within and across days.
AB  - Subjects judged the time-course of the burn caused by 100 ppm capsaicin applied
      to the tongue on Day 1 and Day 5. On Days 2-4, they tasted hard candy containing
      capsaicin. Most subjects did not show adaptation within Day 1, but either
      plateaued after about 16 min or rose monotonically for the entire 34 min.
      Intensity was less on Day 5 and levelled off or declined for most subjects. Data
      were fit to a mathematical model of adaptation. Adaptation across days was
      accounted for by changes in the gains of the three processes.

PMID- 9035247
TI  - Juvenile friends, behavior, and immune responses to separation in bonnet macaque
      infants.
AB  - Individual differences in the response to maternal separation in nonhuman primate
      infants have been attributed to (among other variables) presence or absence of
      processes that may model social support in humans. Alternative attachments to
      other members of the social group buffer the infant against a depressive response
      to maternal separation. This hypothesis was tested in a group of bonnet macaques
      by manipulating the presence or absence of alternative juvenile attachment
      figures (friends) during separation. Infants who retained such attachments showed
      fewer behavioral evidences of depression when separated from their mothers. These
      infants without friends also showed changes in lymphocyte activation by mitogens
      or natural cytotoxicity that were not evident in the infants with juvenile
      friends. Across all separated infants, natural cytotoxicity was positively
      correlated with juvenile affiliative behavior directed toward the infants during
      the separation. These results support the hypothesis that social support,
      available from alternative attachments, can modulate the response to loss, and
      can account for some of the individual differences seen in these responses.

PMID- 9035248
TI  - The satiating potency of hepatic portal glucagon in rats is not affected by
      [corrected] insulin or insulin antibodies.
AB  - To characterize the interactive effects of acute prandial manipulations of
      insulin and glucagon on spontaneous feeding in adult male rats fed ad lib,
      glucagon (G) and insulin (1) or insulin antibodies (IAb) were confused into the
      hepatic portal vein during the first meal of the dark phase. Infusions (3-6 min,
      33 microliters/min) were remotely controlled, and a computerized system recorded
      meal patterns. In Experiment 1, five separate factorial designs were used to test
      the effects of G (1.3 or 13 micrograms/meal) alone, I (1.3 or 2.7 mU/meal) alone,
      or both G + I. The peptides were infused either simultaneously or sequentially (G
      before I). The larger dose of G alone reduced meal size. I neither inhibited
      feeding nor increased the effects of either G dose. In one test, 13
      micrograms/meal G did not block meal size when followed by 2.7 mU I, but this
      antagonism did not occur in a replication. In several tests, there was a trend
      for I to decrease the size of the spontaneous meal that followed the meal during
      which I was infused, but this was statistically significant only once. Intermeal
      intervals were not affected in any test. Experiment 2 tested coinfusions of 20
      micrograms G and polyclonal IAb with an in vitro binding capacity of 40 mU rat
      insulin. G alone reduced meal size, IAb alone increased meal size, and G + IAb
      produced an additive effect. These data extend previous investigations of the
      satiating action of G and I in the rat and indicate 1. that exogenous I does not
      affect the satiating potency of G; 2. that exogenous G and endogenous I elicit an
      additive synergistic inhibition of spontaneous meal size; and 3. that G-induced I
      secretion does not mediate the satiating effect of G.

PMID- 9035249
TI  - Hyposmia for butanol and vanillin in mutant staggerer male mice.
AB  - To address the hypothesis that reproductive deficits in male house mice
      expressing the staggerer mutation are due to chemosensory deficits, we examined
      behavioral responses to odorants. Two-choice tests (butanol or vanillin vs. amyl
      acetate odors) were used to determine behavioral thresholds for butanol, an
      aversive odor, and for vanillin, an attractive odor. Two groups of C57B1/6 male
      mice (one nonmutant group and one mutant group) were studied using an
      olfactometer. Different concentrations of butanol were used: from 5.5 x 10(-4) M
      to 5.5 x 10(-1) M. Vanillin at different concentrations, from 6.6 x 10(-5) M to
      6.6 x 10(-2) M, was presented during the tests after a 1-month period of
      familiarization. Aversive and attractive behavioral thresholds of staggerer mice
      were higher than those of nonmutant mice. The staggerer mutation induces hyposmia
      in mice. This olfactory deficit could explain, at least partially, abnormalities
      in the social and sexual behaviors of staggerer mice.

PMID- 9035250
TI  - Modulation of plasma glucose by the medial preoptic area in freely moving rats.
AB  - The effect of norepinephrine (NE) injection into the medial preoptic area (MPOA)
      on plasma glucose was studied in freely moving male rats. The rats were implanted
      with chronic jugular catheters for blood sampling and with unilateral
      intracerebral cannulas placed just above the MPOA. Blood samples were taken
      immediately before and 5, 10, 15, and 30 min after NE injection. As early as 5
      min after NE injection, plasma glucose levels rose rapidly, reaching a peak at 15
      min poststimulus. The hyperglycemic response to NE injection into the MPOA was
      dose-related within the range of doses tested (10, 20, and 40 nmol). Previous
      administration of phentolamine (50 nmol), but not propranolol (100 nmol), into
      the MPOA blocked the hyperglycemic response to NE injection into the MPOA. The
      increase of plasma glucose induced by NE into the MPOA and the blockade of the
      hyperglycemic response to NE by phentolamine suggest the involvement of an alpha
      adrenergic mechanism in MPOA-mediated hyperglycemia. On the basis of these and
      previous results, we propose that MPOA alpha-adrenergic synapses relay impulses
      activating the sympathetic outflow expressed by neurally mediated hyperglycemia.

PMID- 9035251
TI  - Remote and proximal US preexposure and aging effects in taste aversion learning
      in rats.
AB  - Age as a factor in the effect of proximal and remote unconditioned stimulus (US)
      preexposure on conditioned taste aversion in weanling, young adult, and old rats
      was studied in 2 experiments. In Experiment 1, 6 daily US preconditioning
      exposures attenuated conditioning in weanlings and young adults, but not in old
      rats. In Experiment 2, exposure to a single US 1 h before the conditioning trial
      curtailed conditioning at all age levels. These results are explained in terms of
      age differences in familiarity with the conditioning context and Wagner's
      information-processing model for self- and retrieval-generated disruption of
      conditioning.

PMID- 9035252
TI  - Effect of sustained estradiol release in the intact male rat: correlation of
      estradiol serum levels with actions on body weight, serum testosterone, and
      peripheral androgen-dependent tissues.
AB  - The differential effect of increasing serum estradiol on various parameters in
      the intact male rat was assessed through the use of subcutaneously implanted,
      hormone-laden pellets. The delivery systems were designed to release drug through
      bioerosion at a zero-order rate over a 12-day time-course. Male Sprague-Dawley
      rats (190 to 220 g) were given estrogen pellets at increasing labeled strenghts
      (0, 0.001, 0.01, 0.1, 1.0, 10, 50, and 100 mg). Animals were weighed at various
      intervals before and after implantation. At Day 6, 12, and 26 after drug
      administration, rats were examined for 4 additional parameters, including serum
      estradiol and testoterone concentrations and accessory organ weights (i.e.,
      ventral prostate and seminal vesicles). Serum estradiol levels were consistent
      with pellet potency and lifetime. Increases in body weight were suppressed 50% by
      circulating estradiol levels of approximately 200 pg/mL at Day 6,250 pg/mL at Day
      12, and 285 pg/mL at Day 26. On the other hand, suppression of serum testosterone
      was more sensitive and was decreased 50% by peripheral estrogen levels of 36, 43,
      and 51 pg/mL at Days 6, 12, and 26, respectively. Accessory organ weights
      essentially reflected serum testosterone levels as indicated by their similar
      ED50 values: 50.5, 50.5, and 44.3 pg/mL for the ventral prostate at Day 6, 12,
      and 26, respectively, and 48, 56, and 51.5 pg/mL for the seminal vesicle
      regression at Day 6, 12, and 26, respectively. The data indicate the pellet used
      provided sustained plasma levels of hormone and these constant peripheral levels
      exerted potent pharmacological action. Initial body weight changes seemed to be
      less sensitive to the action of estradiol than serum testosterone or derivative
      properties, such as accessory organ weight.

PMID- 9035253
TI  - Development of heart inter-beat interval variability in preweanling rats: effects
      of exposure to alcohol and hypoxia.
AB  - The effect of alcohol exposure and hypoxia on the development of heart rate and
      heart inter-beat interval (IBI) variability was studied in preweanling rats. Rats
      were artificially reared from postnatal day (PD) 4 through 12 and either exposed
      to alcohol (5 g/kg/day) or hypoxia (2-15-min episodes/day) from PD 4 to 10.
      Control groups consisted of artificially reared and normally reared rats not
      exposed to alcohol or hypoxia. The heart rate and respiration was recorded for 20
      min sessions every other day from PD 5 through 21. Inter-beat intervals and
      measures of their variability caused by respiratory sinus arrhythmia (RSA) were
      computed from the recordings. There was a steady decline in average IBI across
      this age range. There was little change in RSA from PD 5 to 15, followed by a
      large increase in RSA level from PD 15 to 21. The alcohol- and hypoxia-exposed
      rats showed significantly less increase in RSA level on PD 19 and 21. Large
      bradycardias occurred in all groups on PD 5, 9, and 17, and were more prevalent
      in rats exposed to alcohol or hypoxia. These data suggest that neural control of
      the chronotropic functions of the heart undergoes major changes in the late
      preweanling stage, and the changes in neural control are slowed by hypoxia or
      alcohol exposure during the early postnatal period.

PMID- 9035254
TI  - Ovariectomy and estradiol affect postingestive controls of sucrose licking.
AB  - Ovariectomy (OVX) has been shown to increase, and estradiol replacement to
      decrease, meal size in rats. Because little is known about how estradiol
      influences meals, we conducted two experiments to examine the effects of OVX and
      beta-estradiol 3-benzoate (EB) replacement on the microstructure of licking
      behavior. In both experiments, patterns of licking were analyzed in adult female
      Sprague-Dawley rats during an 0.8 M sucrose test meal. In Experiment 1, meal
      microstructure was determined preOVX and 10-12 days postOVX. Rate of licking
      following OVX was not changed during min 1 of the meal, but was significantly
      faster during min 2-4 of the meal (p < 0.03). The numbers of bursts (runs of
      licks separated by 250-500 ms) and numbers of clusters (runs of licks separated
      by > 500 ms) were significantly increased during min 2-4 (p < 0.05). In
      Experiment 2, OVX rats received EB replacement. Rate of licking after EB
      replacement was not changed during min 1 of the meal, but was significantly
      slower during the remainder of the meal (min 2-4, min 5-7, and min 8-10). Burst
      size, cluster size, and interburst interval were less after EB replacement during
      min 5-7 of the test meal (all p < 0.05). Because both OVX and EB replacement
      failed to alter the rate of licking during min 1, estrogen did not appear to
      alter the palatability of sucrose. OVX and EB replacement did appear to affect a
      postingestive mechanism(s) that is engaged within 2-4 min of meal onset.

PMID- 9035255
TI  - Sleep deprivation by the "flower pot" technique and spatial reference memory.
AB  - This study investigated whether paradoxical, or rapid eye movement (REM), sleep
      deprivation (SD) affected spatial memory. SD was induced in male Wistar rats by
      housing them on small platforms over water. They fell into the water if they lost
      muscle tone. Controls were either housed in tanks with large platforms (TC) or in
      normal cages (CC). All rats had free access to food and water. Each day they were
      tested in a place-learning set task using a Morris water maze. The rats were
      released from 6 different starting points (sets) and allowed 2 min to find a
      submerged platform. Two trials were conducted from each starting point. SD caused
      a significant decrement in performance in Trial 1 from Day 2. By Day 4, when
      distance swum to find the platform was plotted against set, area under the curve
      was doubled in SD compared to that in TC and CC rats, indicating a significant
      impairment in reference spatial memory. There was no consistent effect on working
      memory, indicated by Trial 2. SD caused weight loss and increased serum
      corticosterone compared to that in CC rats. There were no differences in
      concentrations of hypothalamic, hippocampal, or cortical catecholamines or their
      metabolites. Serotonin metabolism was elevated in the hypothalamus and
      hippocampus in SD rats. These results indicate that SD induced in rats housed on
      small platforms causes a substantial impairment of reference memory. The memory
      deficit may not be specific to SD because the rats are physically stressed and
      lose some nonREM sleep when housed in these conditions.

PMID- 9035256
TI  - Reduction of the scopolamine-induced impairment of passive-avoidance performance
      by sigma receptor agonist in mice.
AB  - We examined the ameliorating effects of several sigma receptor agonists on
      scopolamine-induced memory impairment in mice. Scopolamine was administered IP 30
      min before the training session. Each sigma receptor agonist was administered 60
      min before or immediately after the training session, or 60 min before the
      retention test in the passive-avoidance performance experiments. (+)-N
      Allylnormetazocine ((+)-SKF-10,047), a prototype sigma 1 receptor agonist, showed
      an ameliorating effect on the scopolamine-induced memory impairment in these 3
      administration schedules, and (-)-SKF-10,047, a stereoisomer with low affinity
      for the sigma 1 receptor subtype, failed to reduce this memory impairment in
      mice. In addition, 1,3-di(2-toly1)guanidine (DTG) and (+)-3-(3-hydroxyphenyl)-N
      (1-propyl)piperizine ((+)-3-PPP), nonselective sigma receptor agonists, did not
      affect this memory impairment. Physostigmine, an acetylcholinesterase (AChE)
      inhibitor, alleviated the scopolamine-induced memory impairment in all these drug
      administration schedules. In addition, (+)-SKF-10,047-induced antiamnesic effect
      was antagonized by the concurrent administration of haloperidol, a sigma receptor
      antagonist, or N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy) phenyl)ethylamine
      monohydrochloride (NE-100), a selective sigma 1 receptor antagonist. These
      findings indicate that the sigma 1 receptor agonist has ameliorating effects on
      all phases of learning and memory processes. This profile of sigma 1 receptor
      agonist is similar to that of an AChE inhibitor.

PMID- 9035257
TI  - The effects of 17 alpha-methyltestosterone, methandrostenolone, and nandrolone
      decanoate on the rat estrous cycle.
AB  - In a series of four separate experiments, the effects of anabolic-androgenic
      steroid (AAS) compounds on the estrous cycle of adult Long-Evans rats were
      examined. Sexual receptivity, vaginal cytology, and body weight were monitored
      throughout a 2-week baseline, AAS treatment, and recovery periods. In Experiments
      1-3, subjects were administered 17 alpha-methyltestosterone, methandrostenolone,
      or nandrolone decanoate at doses selected to mimic the human abuse levels of each
      compound. In these studies, the highest doses of 17 alpha-methyltestosterone (7.5
      mg/kg) and nandrolone decanoate (5.6 mg/kg) disrupted behavioral and vaginal
      cyclicity, whereas the highest dose of methandrostenolone (3.75 mg/kg) appeared
      to have slightly less robust effects. To compare effects on estrous cyclicity
      across AAS compounds, subjects in Experiment 4 received a single high dose (7.5
      mg/kg) of each compound for 2 weeks. At this dose, all AAS compounds interfered
      with vaginal cyclicity, although effects on behavioral cyclicity and uterine
      weight were not uniform. Across all 4 experiments, AAS effects on body weight
      were minimal. The short-term administration of AAS compounds at levels commonly
      used by humans disrupts female neuroendocrine function in a dose-dependent
      manner.

PMID- 9035259
TI  - Sustained stress and fixed interval performance.
AB  - The effects of sustained stress on response rate and temporal patterning (quarter
      life) of rats performing either a previously learned fixed-interval schedule (FI
      60) or learning an FI 60 simultaneously with stress onset were determined. Rats
      lived 24 h/day in operant cages, where they earned all of their food via lever
      pressing. During the stress portion of each experiment, one group of rats was
      able to avoid or escape signalled intermittent footshock (Avoidance/ Escape
      Group), a second group (Yoked) did not have control over shock termination, a
      third group never received shock (Control). Shock trials were presented around
      the clock at approximately 5-min intervals and the stress portion of each study
      lasted 1-2 weeks. We have previously reported that rats tolerate this paradigm
      well and avoid/escape 99% of the shock trials. In rats previously trained on the
      FI task, both rate of responding and quarter-life values were significantly
      decreased on the first day of stress for both the Avoidance/Escape and Yoked
      Groups. Food intakes and quarter-life values were not significantly different
      from the controls by stress Days 3 and 2, respectively. In the acquisition study,
      controls learned the F1 task by Day 4 as judged by quarter-life of responding. FI
      task acquisition was significantly impaired in stressed rats compared to
      controls, not reaching asymptotic performance until Day 9 of stress. There were
      no major differences between the 2 stress groups in either study. These data
      demonstrate that stress may impair both the rate and patterning of behavior, and
      suggest that this rodent paradigm may usefully model some aspects of the effects
      of stress in humans.

PMID- 9035258
TI  - Phase shifts to refeeding in the Syrian hamster mediated by running activity.
AB  - Circadian rhythms in hamsters can be entrained by restricted daily feeding
      schedules. Phase control may be exerted by feeding per se, or by wheel running in
      anticipation of food access. Phase modulation by feeding was examined here by
      depriving hamsters of food for 9-24 h and refeeding at 1 of 7 different zeitgeber
      times on the first day of constant dim light. Significant group mean phase
      advance shifts were observed only following 24 h and 17 h deprivations ending in
      the mid-subjective day, 7 h before the usual time of lights off (mean shifts 28
      min and 66 min, respectively). The largest phase shifts were associated with
      wheel running during the first 6 h of refeeding. When running wheels were locked
      during this time in an additional group, no phase shifts were observed. A trend
      for small phase delays was evident for 14 h deprivations ending at the beginning
      of the subjective night, but no significant group mean or individual shifts were
      observed at other refeeding times. Refeeding after food deprivation, thus,
      appears to have minimal effects on circadian phase in hamsters; wheel running
      associated with refeeding may account for occasional shifts observed.

PMID- 9035260
TI  - Subcortical multiple unit activity changes during rat male sexual behavior.
AB  - Multiple unit activity (MUA) was recorded from the ventral tegmental area (VTA)
      and mesencephalic locomotor region (MLR) during copulatory behavior of freely
      moving male rats. Simultaneous accelerometric recordings of the copulatory pelvic
      thrusting performed by the male rat were taken to precisely correlate in time the
      changes in MUA with well defined elements of copulation. The baseline MUA firing
      rates recorded in the quiet-alert condition in the VTA and in the MLR were
      significantly increased during pursuit of the female by the male; significantly
      higher MUA firing rates were found in the VTA at the 500 ms periods before and
      during the execution of pelvic thrusting in mount, intromission, and ejaculation
      responses as compared to the baseline, and returned to this value when these
      responses ended. The maximum MUA firing rate in the MLR was obtained during the
      execution of pelvic thrusting in each copulatory response, and it remained
      significantly elevated, as compared to the baseline, after thrusting and at the
      postintromission and postejaculatory genital grooming, then decreasing to basal
      values at the initial part of the postejaculatory interval. The fact that the
      highest changes in MUA were related to pelvic thrusting suggests a major
      participation of both structures in the execution of motor copulatory responses.

PMID- 9035261
TI  - Detection of the erect position in the freely-moving human: sensor
      characteristics, reliability, and validity.
AB  - The present report systematically examined a means to electronically detect the
      erect position in the human in the natural setting. The detector was based on
      pressure changes in a glycerin filled tube attached to a subject's leg, and it
      unobtrusively and continuously measured the relative vertical distance between
      the hip and leg. Initial experiments established the reliability of the sensor
      system as a function of 1. different sizes of the tubing, 2. different amounts of
      air in the glycerin and 3. different ambient temperatures (6 degrees-32 degrees
      C). Then, in a laboratory study of normal adults, the detector was seen to
      discriminate sitting from standing and (when activity data were included) these
      two behaviors, in turn, from walking. The detector also accounted for significant
      differences in HR seen in the standing, as opposed to the sitting, position. In
      addition, when subjects carried the detector during their daily activities and
      provided information about their activities using an experience sampling
      procedure, sitting was discriminated from standing and walking with acceptable
      diagnostic characteristics. Thus, sitting was detected with a sensitivity of
      86.1% (correct detection of all occasions when sitting actually occurred). a
      positive predictive value of 92.6% (occasions that the detector was right when it
      indicated sitting), and a negative predictive value of 80.7% (occasions that the
      detector was right when it indicated sitting). Finally, we demonstrated in two
      additional ways the direct benefit of our detector in behavioral studies in the
      natural environment. First, with the detector, we could confirm that a subject
      had performed simple activities and errands while not under close supervision.
      Second, cigarette smoking in the natural environment was shown to increase HR,
      but only when the subjects were sitting. It was concluded that our detector can
      be effectively applied to the identification of the sitting vs. the erect
      position in humans in the natural setting, and that this information may be
      necessary to interpret behavioral and physiological effects seen in such
      subjects.

PMID- 9035262
TI  - Schedule-induced masseter EMG in facial pain subjects vs. no-pain controls.
AB  - Empirical reports suggest that oral habits (e.g., teeth clenching) may be
      behavioral mediators linking stress to muscle hyperreactivity and the development
      of facial pain. Another report suggests that excessive behavioral adjuncts
      develop in conjunction with fixed-time stimulus presentation. The present study
      assessed the extent to which the oral habits exhibited by facial pain patients
      are schedule-induced. Subjects with Temporomandibular Disorder (TMD)
      symptomatology (n = 15) and pain-free controls (n = 15) participated in a 4-phase
      experiment (adaptation, baseline, task, recovery) designed to elicit schedule
      induced behaviors. Self-report of oral habits and negative affect were recorded
      after each phase. Objective measures of oral habits were obtained via behavioral
      observation and masseter EMG recordings. Results revealed that negative arousal
      significantly increased during the fixed-time (FT) task and was also associated
      with increased oral habits among the TMD subjects. Moreover, 40% of the TMD
      subjects and none of the controls exhibited a pattern of EMG elevations in the
      early part of the inter-stimulus interval that met a strict criteria for
      scheduled-induced behavior per se. Taken together, these results suggest that the
      TMD subjects were engaging in schedule-induced oral habits. The adjunctive
      behavior literature seems to provide a plausible explanation as to how oral
      habits develop and are maintained in TMD patients, despite their painful
      consequences.

PMID- 9035263
TI  - Antinociceptive effects of palatable sweet ingesta on human responsivity to
      pressure pain.
AB  - Palatable sweet ingestion produces a morphine-like analgesia in both rats and
      human infants (2-5). To determine whether palatable sweet ingesta induces
      antinociception in human adults, 60 university students (30 men, 30 women) were
      exposed to a pressure algometer both before and after consuming either a sweet
      soft drink, filtered tap water, or nothing (Experiment 1). Pain responsivity was
      assessed with four pain measures: threshold, tolerance, and visual analogue scale
      (VAS) ratings of intensity and unpleasantness. Results showed that women who
      consumed either soft drink or water reported increased pain tolerance and VAS
      ratings at posttreatment compared with those receiving nothing. However,
      differences between groups were not found for men. Moreover, compared to men,
      women reported lower pain thresholds and tolerances and rated the pain as more
      intense. In Experiment 2, 40 women consumed either nothing or foods that they
      rated previously as palatable (chocolate-chip cookies), unpalatable (black
      olives), or neutral (rice cakes). Women who consumed the palatable sweet food
      showed increased pain tolerance compared with those receiving the unpalatable
      food, the neutral food, or nothing. These data constitute the first demonstration
      that "palatability-induced antinociception" (PIA) can occur in human adults.

PMID- 9035264
TI  - Extinction of a conditioned taste aversion in rats: I. Behavioral effects.
AB  - The literature is divided over whether a conditioned taste aversion (CTA) can be
      fully extinguished. In Experiment 1, we created a powerful aversion in 54 rats by
      pairing the taste of 0.0025 M NaSaccharin (CS) with intraperitoneal injections of
      127 mg/kg LiCl (US) on 3 occasions. We then offered 23-h deprived rats
      NaSaccharin for 10 min/day to observe the course of recovery. Extinction occurred
      in three phases: static, dynamic, and asymptotic. During the static phase (mean =
      9.6 days), rats consumed the CS at < 10% of their preconditioned rate. With
      dynamic recovery (6.0 days), they increased acceptance to > 80% of
      preconditioning levels. Finally, they achieved asymptote (3.1 days) at 100%
      acceptance. In Experiment 2, we used 8 additional conditioned rats and 8
      unconditioned controls. We followed the same 1-bottle extinction procedure and,
      again, obtained 100% acceptance. Then we offered both NaSaccharin and water for 8
      days at 23 h/day and monitored lick patterns every 6 s to determine taste
      preferences. The conditioned animals consumed less NaSaccharin than controls on
      Day 1, and less NaSaccharin as a percentage of total fluid as late as Day 3. For
      the last 5 days of 2-bottle preference testing, there were no significant
      differences between the groups with regard to 1. volume of NaSaccharin or water
      consumed, 2. percentage of total fluid taken as NaSaccharin, 3. consumption of
      each fluid associated with a meal or taken spontaneously, 4. intake during the
      light or dark periods, or 5. the characteristics of ingestion, including number
      of drinking bouts, duration of bouts, number of licks/bout, and rate of licking.
      Therefore, a robust CTA is subject to complete behavioral extinction.

PMID- 9035265
TI  - Cardiorespiratory components of defense reaction elicited from paraventricular
      nucleus.
AB  - The present study was conducted to test the hypothesis that the paraventricular
      nucleus of the hypothalamus (PVN) is involved in the mediation or modulation of
      the cardiorespiratory components of the defense reaction (DR) in rabbits.
      Electrical stimulation of the PVN elicited increases in blood pressure and heart
      rate, hyperventilation, decreased blood flow to the visceral organs, and an
      increase in blood flow to the hindlimbs that was mediated by an atropine
      sensitive vasodilation system. This response pattern is nearly identical to the
      one that is elicited by electrical stimulation of the hypothalamic defense area.
      In addition, the cardiomotor component of the baroreceptor reflex was observed to
      be suppressed during electrical stimulation of the PVN. Previous studies have
      shown that electrical stimulation of the hypothalamic defense area also leads to
      inhibition of the cardiomotor component of the baroreceptor reflex. The results
      of the present study provide evidence that the PVN is involved in the mediation
      or modulation of the defense reaction.

PMID- 9035266
TI  - Food neophobia in humans: effects of manipulated arousal and individual
      differences in sensation seeking.
AB  - The study examined the effects of manipulated arousal and the trait of Sensation
      Seeking on willingness to taste novel foods (as assessed by means of a choice
      task). Arousal was manipulated by having subjects play an exciting, neutral, or
      boring video game. In line with predictions from optimal level of arousal
      theories, subjects chose more novel foods when manipulated arousal was low (vs.
      neutral) and fewer novel foods when manipulated arousal was high (vs. neutral).
      There was no main effect of individual differences in optimal level of arousal as
      assessed by the Sensation Seeking Scale; however, an interaction between the two
      independent variables revealed high-sensation seekers to try more novel foods
      than lows under conditions of low arousal.

PMID- 9035267
TI  - Sexually arousing events and relapse to heroin-seeking in sexually experienced
      male rats.
AB  - We have shown previously, using a reinstatement procedure, that both priming
      injections of heroin and exposure to footshock stress reinstate heroin-taking
      behavior following prolonged drug-free periods. In the present study, we examined
      the effect of another highly arousing event, exposure to a sexually active
      female, on reinstatement of heroin-seeking. Male rats were first given sexual
      experience, being allowed to copulate on 4 occasions with sexually active females
      and were then trained to self-administer heroin (100 micrograms/kg per infusion,
      IV) for 4 3-h sessions/day for 5-6 days and 1 6-h session/day for an additional 6
      days. Extinction sessions were then given for 4 days, 6-h/day, during which
      saline was substituted for heroin. On tests for reinstatement, males were
      presented with: 1. The wire-mesh side of an empty cage (baseline condition), 2.
      the sight, odor, and smell of a sexually inactive female, 3. the sight, odor, and
      smell of a female in heat, 4. a female in heat, and allowed to copulate, 5.
      intermittent footshock (15 min, 0.5 mA, 0.5 s on, mean off period of 40 s), or 6.
      a priming injection of heroin (0.25 mg/kg, SC). Reinstatement of heroin-taking
      behavior was observed after exposure to the priming injection of heroin and to
      footshock stress. Reinstatement of heroin-taking behavior was not induced by
      exposure to the females in any of the conditions. Thus, motivational arousal, as
      such, does not appear to be a sufficient stimulus for relapse to heroin-taking.

PMID- 9035268
TI  - Diet-induced thermogenesis and satiety in humans after full-fat and reduced-fat
      meals.
AB  - Diet-induced thermogenesis was measured during and after a full-fat lunch, an
      identical but reduced-fat, reduced-energy lunch, and an iso-energetic reduced-fat
      lunch in 32 normal-weight men and women, age 35-55. Hunger and satiety were
      scored during and after the lunches, and their relationship to diet-induced
      thermogenesis was assessed. Diet-induced thermogenesis was relatively higher
      after the reduced-fat, reduced-energy lunch compared to the full-fat lunch (6.7%
      vs. 5.2%; p < 0.05). The respiratory quotients were significantly lower after the
      full-fat lunch than after the 2 reduced-fat lunches (p < 0.05). After the iso
      energetic reduced-fat lunch, hunger scores were significantly reduced and satiety
      scores significantly increased (p < 0.05) until 1800 h. compared to the other 2
      lunches. Satiety scores were positively related to the magnitude of diet-induced
      thermogenesis expressed as an absolute increase in metabolic rate during and
      after the meal. We conclude that hunger and satiety scores, substrate
      utilization, and diet-induced thermogenesis showed clear and different short-term
      responses to diets that differed with respect to the percentage energy from fat
      and/or the energy content of the meal.

PMID- 9035269
TI  - The role of gastric and postgastric sites in glucose-conditioned flavor
      preferences in rats.
AB  - Two experiments examined the role of gastric and postgastric contributions in the
      development of flavor preferences in rats. During training trials, food-deprived
      rats consumed, on alternate days, a cue flavor paired with glucose infusions and
      another flavor paired with water infusions. Preferences were assessed in choice
      tests between the two cue flavors without infusions. The first experiment
      compared preferences conditioned to a flavor paired with intraduodenal (ID)
      glucose infusions to those paired with intragastric (IG) infusions. ID glucose
      conditioned preferences were as strong as that of IG glucose. The second
      experiment examined whether the actions of glucose in the stomach alone were
      sufficient to condition flavor preferences. Glucose infusions were restricted to
      the stomach with an inflated pyloric cuff and then removed at the end of 30-min
      training sessions before the cuff was deflated. Rats trained with this procedure
      did not develop a reliable flavor preference. Flavor preferences were obtained,
      however, when the cuff was inflated for 30 min after the end of the daily
      training sessions, or when the cuff was inflated during the training sessions but
      then deflated without removing the infused glucose. Both of these procedures
      allowed at least some of the infused glucose to empty into the intestine. Taken
      together, the results indicate that information from the stomach is neither
      necessary nor sufficient to produce glucose-conditioned flavor preferences. Such
      preferences are reinforced by the intestinal and/or postabsorptive actions of
      glucose.

PMID- 9035270
TI  - Assisted suicide.

PMID- 9035271
TI  - Digital radiography using storage phosphor technology. Introduction.

PMID- 9035272
TI  - Case of the season. Pyomyositis of the left short head of the biceps femoris.

PMID- 9035273
TI  - Digital radiography using storage phosphor technology: how computed radiography
      acquires data.

PMID- 9035274
TI  - Computed radiography for the radiological technologist.
AB  - CR has emerged as a general imaging technology for successful imaging of the
      chest, abdominal, musculoskeletal, and pediatric anatomy. For the general
      radiographer, CR is both celebrated and scorned for its complex function, and
      requires thorough ongoing training for the technologists to produce consistently
      high image quality. Digital radiography's unique separation of detector, display,
      and archive add a flexibility over screen-film technology for moving, storing,
      printing, and viewing plain radiographic images. CR technology is now a viable
      solution for those wishing to embrace the electronic and digital revolution in
      medicine. Although the system has less spatial resolution than screen-film
      technology, the strength of postacquisition image processing to enhance pathology
      and view obscured anatomy makes CR imaging attractive to technologists and
      radiologists. CR is a new modality for the general radiographer that, when put
      into the hands of a well-trained technologist, produces images of beautiful
      diagnostic quality.

PMID- 9035275
TI  - Image processing in digital radiography.
AB  - Image processing is a critical part of obtaining high-quality digital
      radiographs. Fortunately, the user of these systems does not need to understand
      image processing in detail, because the manufacturers provide good starting
      values. Because radiologists may have different preferences in image appearance,
      it is helpful to know that many aspects of image appearance can be changed by
      image processing, and a new preferred setting can be loaded into the computer and
      saved so that it can become the new standard processing method. Image processing
      allows one to change the overall optical density of an image and to change its
      contrast. Spatial frequency processing allows an image to be sharpened, improving
      its appearance. It also allows noise to be blurred so that it is less visible.
      Care is necessary to avoid the introduction of artifacts or the hiding of
      mediastinal tubes.

PMID- 9035276
TI  - Digital radiography of the chest.
AB  - Digital radiography is an appropriate method for both bedside and in-department
      chest radiographs. Its major advantage in bedside chest radiography is its
      control of the displayed optical density of these radiographs. With dynamic range
      control processing, it improves the visibility of tubes and lines superimposed on
      the mediastinal tissues. When used for in-department chest radiography, it may
      offer slight advantages in the evaluation of disease in the mediastinum, but in
      general is equivalent to film-screen chest radiography. The main reasons for
      using digital chest radiography for in-department chest radiographs relate mainly
      to its use as a data entry point method of projection radiography for high
      quality teleradiology or for its use in a picture archiving and communication
      system. Apart from these advantages, there is no reason to change from
      conventional to digital chest radiographs. Digital radiographs are, with certain
      systems, printed at smaller than life size. Because of this, there is a necessary
      period of learning as radiologists adjust to the new image size. The most
      important change in radiologists' work pattern appears to be the need to sit
      closer to the film. Findings of disease are smaller, but, with experience, just
      as easy to see.

PMID- 9035277
TI  - Dual-energy radiography.

PMID- 9035278
TI  - Storage phosphor digital mammography.
AB  - Digital mammography using storage phosphor CR is still in the investigational
      stage. It is the only digital mammography system that has been tested in
      preliminary clinical trials with promising early results. Further clinical
      studies are needed to assess the impact of the limited spatial resolution of
      storage phosphor technology on its application as a digital screening mammography
      system. Further studies also are needed to determine the optimum image processing
      parameters needed in digital mammography.

PMID- 9035279
TI  - Computed radiography in pediatric radiology.

PMID- 9035280
TI  - Computed radiography in musculoskeletal imaging.
AB  - In conclusion, CR offers many advantages in comparison with conventional
      radiography. Musculoskeletal radiology particularly benefits from the wide
      dynamic range and image-processing capabilities of CR. Most studies have not
      shown a statistically significant difference in observer performance (diagnostic
      accuracy) of CR in comparison with conventional radiography in musculoskeletal
      applications. In addition, dose reduction in the range of 25% to 50% is possible
      with many musculoskeletal images. However, disadvantages are also apparent and
      include reduced spatial resolution, increased noise, and change in image size and
      format. Overall, the advantages of CR and digital technology outweigh its
      limitations and for these reasons continue to promote the conversion from
      conventional radiography.

PMID- 9035281
TI  - Prognostic factors to predict outcome following the administration of
      hypertonic/hyperoncotic solution in hypovolemic patients.
AB  - Hypertonic solutions effectively improve hemodynamic parameters in patients
      admitted to the emergency room. However, no significant differences in outcome
      were observed compared with standard isotonic treatment in most previously
      published studies. This study evaluates pretreatment prognostic factors that
      predict a beneficial effect of hypertonic solution in patients admitted to the
      emergency room with hemorrhagic hypovolemia in a prospective double-blind
      fashion. The patients (n = 212) were randomized upon admission to receive 250 mL
      intravenous (i.v.) bolus of hypertonic 7.5% NaCl + 6% dextran (HSD, n = 101), or
      isotonic 0.9% NaCl solutions (IS, n = 111) as the first treatment, followed by
      standard resuscitation. Pretreatment factors assessed were sex, age, cause of
      hypovolemia, revised trauma score (RTS), Glasgow index, and mean arterial
      pressure (MAP) on admission. Both groups were compared for survival at 24 h and
      30 days postadmission. Infused volumes were registered. HSD administration
      significantly increased MAP and reduced i.v. crystalloid infusions to maintain
      hemodynamic parameters, compared with IS. There was no difference between groups
      in the number of blood transfusions administered. Overall complication rates in
      both groups were similar (24%). There was a significant difference (p < .03) in
      overall (30 days) survival rate between HSD (73%) and IS (64%) groups. The 24 h
      survival rate was significantly lower in IS (72%) compared with HSD (87%); p <
      .01. Multivariate analyses showed that RTS and MAP were identified as independent
      predictors for 24 h survival in the group that received HSD. When evaluated for
      overall survival rate, hypertonic infusion benefited significantly only patients
      with MAP < 70 mmHg (p < .01).

PMID- 9035282
TI  - Studies on polymorphonuclear leukocyte bactericidal function: the role of
      exogenous cytokines.
AB  - We investigated the effects of exogenous cytokines (interleukin (IL)-8, tumor
      necrosis factor (TNF)-alpha, and IL-1 beta) on polymorphonuclear neutrophil (PMN)
      bactericidal activity against both Staphylococcus aureus and Escherichia coli.
      Both baseline and IL-8-stimulated PMN bactericidal activity against E. coli, but
      not against S. aureus, declined significantly from 0 to 240 min. The decline in
      bactericidal activity was prevented by TNF-alpha, but not IL-1 beta. Bactericidal
      activity against both E. coli and S. aureus declined as PMN:target ratios went
      from 20:1 to 5:1. TNF-alpha and IL-1 beta preserved bactericidal activity even at
      a 5:1 PMN:target ratio against E. coli, whereas all three cytokines preserved
      bactericidal activity at a 5:1 PMN:target ratio against S. aureus. Dose-response
      curves demonstrated significant increases in bactericidal activity with
      physiologically relevant concentrations of cytokines (IL-8: .1-10 ng/mL; TNF
      alpha: 1-10(2) U/mL; and IL-1 beta: 0-10 ng/mL). Binding of cytokine receptors
      with monoclonal antibodies directed against IL-8R Type A, TNF-alpha R (p60) or
      (p80), and IL-1 beta R Type I significantly reduced the effect of individual
      cytokines on PMN bactericidal activity. Inhibition of terminal, but not proximal,
      products of the PMN oxidative burst significantly reduced the effect of exogenous
      cytokines on PMN bactericidal activity. These results demonstrate that individual
      cytokines at relatively low concentrations enhance PMN bactericidal activity via
      oxidant-dependent mechanisms and that inhibiting cytokine functions may not be
      advantageous at infectious foci in vivo.

PMID- 9035283
TI  - Inhibition of NF-kappa B activation by dimethyl sulfoxide correlates with
      suppression of TNF-alpha formation, reduced ICAM-1 gene transcription, and
      protection against endotoxin-induced liver injury.
AB  - The effect of the free radical scavenger dimethyl sulfoxide (DMSO) on activation
      of the nuclear transcription factor kappa B (NF-kappa B) was investigated in an
      experimental model of endotoxin-induced liver failure. In galactosamine
      sensitized C3Heb/FeJ mice, DMSO (10 mL/kg) effectively inhibited endotoxin
      induced hepatic NF-kappa B activation, suppressed TNF-alpha levels in plasma by
      86%, attenuated intercellular adhesion molecule-1 (ICAM-1) mRNA formation,
      blocked hepatic neutrophil accumulation by 79%, and reduced liver injury by 80%.
      In galactosamine-sensitized mice treated with 20 micrograms/kg murine TNF-alpha,
      DMSO moderately reduced hepatic NF-kappa B and decreased ICAM-1 mRNA formation
      and liver injury by 83%, but had no significant effect on hepatic neutrophil
      accumulation. Thus, DMSO was able to inhibit, at least in part, two critical NF
      kappa B-dependent steps in the pathophysiology, i.e., TNF-alpha formation and
      ICAM-1 gene transcription. Our data suggest the involvement of redox-sensitive
      events in the signal transduction pathway of NF-kappa B activation in the liver.
      Inhibition of NF-kappa B activation correlates with the reduced activation of
      proinflammatory genes in vivo and the subsequent attenuation of inflammatory
      liver injury. Thus, antioxidants that are NF-kappa B inhibitors may have
      therapeutic potential in endotoxin shock and sepsis.

PMID- 9035284
TI  - NF-kappa B and reactive oxygen intermediates.

PMID- 9035285
TI  - Organ damage is preceded by changes in protein extravasation in an experimental
      model of multiple organ dysfunction syndrome.
AB  - Our objective was to determine the serial evolution of vascular permeability as
      measured by protein extravasation in various organs during the development of
      zymosan-induced multiple organ dysfunction syndrome (MODS). We evaluated the
      biodistribution of 111Indium-labeled nonspecific polyclonal immunoglobulin G
      (111In-IgG). On days 2, 5, 8, and 12 after intraperitoneal challenge with 1 mg/g
      zymosan, mice were killed. Heart, liver, spleen, kidneys, and the mesenteric
      lymph node complex and tissue samples of muscle, ileum, and colon were dissected
      free and weighed. 24 h before death, 10 micrograms of IgG labeled with 2 MBq
      111In was injected i.v. Relative organ weights (ROW), wet to dry weight ratios
      (WDR), and a permeability index (PI) were calculated. ROW increased gradually
      until day 12. WDR also increased gradually in most organs. Lung WDR, however,
      initially increased, with a subsequent return to normal. Splenic WDR did not
      change over time. Liver, spleen, ileum, and colon PI were the highest on day 2,
      followed by a decrease toward normal. Lung PI showed a triphasic course with peak
      values at days 2 and 12. Mesenteric lymph node complex-PI was continuously
      elevated. WDR (tissue edema) and PI (protein extravasation) have different
      courses in various organs. Most organs displayed an early increase in PI,
      followed by a late decrease, while ROW (organ damage) was still increasing. It
      appears that organ damage is preceded by an increased protein extravasation.

PMID- 9035286
TI  - Endothelial structural integrity is maintained during endotoxic shock in an
      interleukin-1 type 1 receptor knockout mouse.
AB  - The derangement of arterial endothelial cell morphology is a good indicator of a
      severe shock state. Because interleukin (IL)-1 has been implicated in this
      process, we examined the structural integrity of aortic endothelial cells in
      conjunction with serum IL-6 concentrations and nitric oxide levels, which are
      known to increase during endotoxemia in animals genetically devoid of the type 1
      IL-1 receptor. Endotoxin (10 mg/kg Escherichia coli, injected intraperitoneally)
      (LD100) or saline vehicle was administered to adult male C57BL/129J wild-type
      control mice and C57BL/129J knockout mice possessing a homozygous deletion of the
      type 1 IL-1 receptor. The integrity of the aortic endothelium was determined by
      comparisons of ultrastructure. Mice injected with sterile vehicle showed normal
      endothelial ultrastructure with intact membranes. Wild-type and knockout control
      animals receiving saline vehicle showed a complete aortic endothelium (29.11 +/-
      .27 and 30.85 +/- .21 intact endothelial cells per millimeter of internal elastic
      lamina (IEL), respectively, p = N.S.). Endotoxin-treated wild-type animals showed
      extensive endothelial damage with most sections showing only denuded IEL on the
      luminal surface (1.83 +/- .38 cells/mm IEL, p < .001 vs. control). Knockout
      animals treated with endotoxin showed complete maintenance of endothelial
      structural integrity (34.08 +/- .57 cells/mm IEL, p < .001 vs. endotoxin-treated
      wild type) with ultrastructural morphology appearing identical to those given
      saline vehicle. Also, no apparent correlation was observed between serum IL-6
      concentrations or serum nitric oxide levels and aortic endothelial damage. The
      maintenance of endothelial integrity in animals devoid of the IL-1 receptor
      confirms earlier observations of endothelial cell protection with IL-1 receptor
      antagonism and suggests that IL-1 contributes significantly to sepsis-induced
      endothelial damage.

PMID- 9035287
TI  - Nitric oxide synthase is not involved in cardiac contractile dysfunction in a rat
      model of endotoxemia without shock.
AB  - Endotoxin and proinflammatory cytokines induce nitric oxide synthase (NOS), and
      nitric oxide (NO) plays an important role in promoting endotoxin shock. However,
      the role of NOS in endotoxemic cardiac contractile dysfunction is not defined. To
      determine whether endotoxemic cardiac contractile dysfunction involves NOS, the
      present study used a rat model of endotoxemia without shock and examined the
      effects of glucocorticoids (dexamethasone, a potent inhibitor of inducible NOS,
      iNOS, expression), isoform nonselective NOS inhibitor (NG-monomethyl-L-arginine,
      L-NMA) and iNOS selective inhibitor (S-methylisothiourea sulfate, SMT) on cardiac
      contractile dysfunction. A sublethal dose of endotoxin (from Salmonella
      typhimurium, .5 mg/kg, i.p.) was given to adult rats, and left ventricular
      developed pressure (LVDP) examined by Langendorff technique was attenuated in
      hearts isolated at 4 or 6 h (66.7 +/- 3.4 and 60.3 +/- 5.5 mmHg, respectively, p
      < .05 vs. 102 +/- 2.4 mmHg in saline control) after endotoxin treatment.
      Pretreatment of rats with dexamethasone (4.0 mg/kg, i.v., -30 min) partially
      abolished endotoxin-induced contractile dysfunction at 6 h (LVDP 87.6 +/- 6.8
      mmHg, p < .05 vs. endotoxin alone at 6 h). However, pretreatment with L-NMA (30
      mg/kg, i.v., -5 min) or SMT (5.0 mg/kg, i.v., -1 min) failed to prevent the
      contractile dysfunction. Moreover, infusion of L-NMA or SMT in vitro could not
      restore contractile function in hearts isolated at 6 h after endotoxin treatment.
      In contrast, inhibition of NOS with L-NMA or SMT in vitro further attenuated
      coronary flow in endotoxin-treated hearts. Thus, endotoxemic cardiac contractile
      dysfunction in this non-shock rat model may not involve NOS, and inhibition of
      NOS may deteriorate coronary perfusion in endotoxemic heart.

PMID- 9035288
TI  - Effect of hypertonic saline/dextran on post-stenotic myocardial perfusion,
      metabolism, and function during resuscitation from hemorrhagic shock in
      anesthetized pigs.
AB  - Resuscitation using small volumes of hypertonic saline solutions normalizes
      cardiac output without fully restoring arterial pressure. This study compared the
      efficacy of either 7.2% saline/10% dextran 60 (HSDex) or the identical sodium
      load of normal saline (NS) to improve regional myocardial blood flow (MBF),
      contractile function, and oxygen metabolism in the presence of a critical
      coronary stenosis. Fourteen anesthetized, open-chest pigs (25 +/- 3.6 kg) were
      instrumented to assess left anterior descending coronary artery (LAD) flow, post
      stenotic oxygen, and lactate metabolism, regional myocardial segment shortening
      (SS, sonomicrometry), and MBF (radioactive microspheres). After implementation of
      a critical LAD-stenosis, shock was induced by hemorrhage (mean arterial pressure
      (MAP) 45-50 mmHg for 75 min). Resuscitation was started by infusion (2 min) of
      either HSDex (n = 7,10% of blood loss) or NS (n = 7, 80% of blood loss); 30 min
      later 6% dextran 60 (10% of blood loss) was administered in both groups. The LAD
      stenosis did not affect myocardial metabolism, SS, or MBF at rest. After
      hemorrhage, MBF remained unchanged from baseline in non-stenotic but decreased by
      53% in post-stenotic myocardium (p < .05). The endo-epicardial flow ratio fell
      below 1.0 in both areas. SS decreased by 10-15% only in post-stenotic myocardium
      (p < .05). Resuscitation with both HSDex and NS restored cardiac index (CI) but
      not MAP. MBF increased above baseline values with either solution in non-stenotic
      while it remained at shock levels in post-stenotic myocardium, where ischemia
      persisted as evidenced by lactate production and depressed SS. Neither in non
      stenotic nor in post-stenotic myocardium was the epi-endocardial flow ratio
      normalized upon resuscitation with HSDex or NS. We conclude that in the presence
      of a flow-limiting coronary stenosis, initial fluid resuscitation with both HSDex
      and the identical sodium load of NS failed to restore perfusion pressure,
      redistributed MBF in favor of normally perfused myocardium, and did not reverse
      ischemia in post-stenotic myocardium.

PMID- 9035289
TI  - Small intestinal mucosal pH and lactate production during experimental ischemia
      reperfusion and fecal peritonitis in pigs.
AB  - The aim of this study was to investigate mucosal pH and lactate production in a
      porcine model of ischemia/reperfusion and sepsis using both tonometry and a
      technique for segmental intestinal perfusion. Eighteen pigs (17-23 kg) were
      anesthetized and mechanically ventilated. They were divided into three groups and
      followed for 4 h. Group C (n = 6) served as controls. In the ischemia/reperfusion
      group (I/R; n = 6), the superior mesenteric artery was totally occluded for 60
      min. In group P (n = 6), sepsis was induced by fecal peritonitis. Cardiac index
      (CI) was determined by thermodilution and blood flow in the superior mesenteric
      artery (QSMA), using a Transonic flow probe. Intramucosal pH (pHi) was calculated
      using tonometry. A special balloon tube for segmental perfusion was introduced in
      the midileum for lactate measurement. Lactate and oxygen saturation were measured
      in arterial blood and in the superior mesenteric vein. CI, QSMA, pHi, and lactate
      in blood and perfusate remained unchanged in controls. Occlusion of intestinal
      blood flow induced a fall in pHi from 7.28 +/- .02 to 6.76 +/- .04, a marked rise
      in lactate in the perfusate, and an increased arteriovenous lactate difference.
      During reperfusion, pHi tended to return to baseline values. Lactate in the
      perfusate and the arteriovenous lactate difference decreased. In sepsis there was
      a continuous reduction in CI and QSMA to 45 +/- 13% and 40 +/- 20% of baseline,
      respectively. pHi decreased moderately from 7.22 +/- .09 to 6.98 +/- .25. Lactate
      remained unchanged in blood and perfusate. Microscopic mucosal injury was
      observed in all animals subjected to ischemia/reperfusion and in three of six
      pigs in group P. A good association between pHi and lactate production was seen
      in ischemia/reperfusion. However, in sepsis, lactate in superior mesenteric
      venous blood or in intestinal perfusate did not increase, despite the fall in
      pHi. The mechanism causing ischemic mucosal injury has different characteristics
      in sepsis and in ischemia caused by arterial occlusion.

PMID- 9035290
TI  - Interleukin-6 and tumor necrosis factor production in an enterocyte cell model
      (Caco-2) during exposure to Escherichia coli.
AB  - Data linking interactions between bacteria and the intestine with elevated serum
      cytokine levels has led to the concept of the gut as a cytokine-producing organ.
      An in vitro cell culture model was used to investigate the potential role of
      intestinal mucosa within this paradigm. Polarized monolayers of human enterocytes
      (Caco-2) were grown in a two compartment system where the apical and basal
      aspects of the membrane could be studied. Supernatant was collected at 0, 1, 3,
      6, and 24 h after the monolayer was exposed (apically or basally) to 10(2),
      10(5), or 10(8) colony-forming units of Escherichia coli C25/mL and saved for
      interleukin (IL)-6 and tumor necrosis factor (TNF) bioassay analysis. Caco-2
      cells (not bacterially challenged) secreted significant amounts of constitutive
      IL-6, but not TNF, into the apical and basal chambers. Both cytokines levels were
      increased in a dose-dependent fashion (p < .05) after the E. coli challenge. This
      stimulated cytokine response was polar, in that the highest cytokine levels were
      at the side of the bacterial challenge and were most notable at the highest dose
      (10(8) colony-forming units/mL) of E. coli C25 tested. Caco-2 cells produce IL-6
      and TNF in a dose-dependent fashion in response to E. coli C25 and the magnitude
      of this response is maximal on the side of the bacterial challenge. This data
      supports the hypothesis that bacterially challenged human enterocytes may be
      important producers of cytokines.

PMID- 9035291
TI  - Interleukin-1 and tumor necrosis factor alter plasma concentration and interorgan
      fluxes of taurine in dogs.
AB  - We examined the effects of interleukin-1 beta (IL-1), tumor necrosis factor
      (TNF), and alanylglutamine (Ala-Gln) infusion on the plasma concentrations and
      interorgan fluxes of taurine and taurine precursors, including methionine and
      serine, using chronically catheterized awake dogs. In the first study, the dogs
      received 5 micrograms/kg/h of either human recombinant IL-1 or TNF intravenously
      for 2 h. Taurine fluxes in the liver and gut were calculated by blood flows and
      arteriovenous differences during infusion and for 2 h after discontinuation of
      the cytokine infusions. The 2 h continuous infusions of TNF and IL-1 resulted in
      60 and 90% increases, respectively, in the arterial plasma taurine concentration.
      Hepatic taurine flux changed from uptake to release after 2 h of continuous IL-1
      infusion. In the second study, we investigated whether Ala-Gln infusion affects
      taurine metabolism under normal and stress conditions. The dogs were given a
      constant 2 h intravenous infusion of IL-1 or saline. Ala-Gln (6 mumol/kg/min) was
      infused simultaneously during the second hour. Plasma concentrations and fluxes,
      across the liver, gut, and lung, of taurine and taurine precursors were studied.
      IL-1 administration increased the plasma concentration, hepatic release, and lung
      uptake of taurine. Ala-Gln infusion did not affect either plasma concentrations
      or organ fluxes of taurine. These data suggest that cytokines play a role in
      taurine metabolism under stress conditions.

PMID- 9035292
TI  - Risk to surgeons: my experience in surgically treating patients with HIV.

PMID- 9035293
TI  - Evaluating the rational extent of dissection in radical esophagectomy for
      invasive carcinoma of the thoracic esophagus.
AB  - To define the rational extent of dissection in radical esophagectomy for
      esophageal cancer, survival was studied according to nodal status in 154 patients
      undergoing extended radical esophagectomy. The incidence of cervical metastasis
      in patients with upper or middle esophageal tumors did not differ between those
      with favorable (grade N < or = 4) or unfavorable (grade N > or = 5) lymph node
      status, at 28.6% vs 20%, respectively. On the other hand, in patients with lower
      esophageal tumors, the incidence of cervical metastasis was significantly lower
      in those with favorable grade (grade N < or = 4) node status than in those with
      unfavorable grade (grade N > or = 5) node status, at 6.5% vs 46.7%, respectively.
      Survival did not differ in patients with upper or middle esophageal tumors
      according to whether they had regional (n = 42) or distant (n = 15) lymph node
      metastases, the 5-year survival rates being 11.6% vs 25%, respectively. However,
      in patients with lower esophageal tumors, none of 10 patients with distant node
      metastases survived for more than 4 years, whereas the survival rate was 43.7% at
      5 years for 36 patients with regional node metastases. These results show that
      cervical lymphadenectomy should only be performed as part of radical
      esophagectomy in those patients with upper or middle esophageal cancer.

PMID- 9035294
TI  - Treatment of esophageal cancer in patients over 80 years old.
AB  - A total of 828 patients with esophageal cancer were treated at the Second
      Department of Surgery of Tokai University in the 20-year period from 1975 to June
      1994, including 45 patients over 80 years old. We reviewed these elderly patients
      to assess the optimum therapeutic approach for such individuals. In recent years,
      the number of elderly patients with esophageal cancer has steadily been
      increasing. Advanced cancer is more common among this group, but early cancer has
      also been detected more frequently in recent years. Of the 45 elderly patients
      (80%) in our series, 36 were encountered in the last 10 years. As 28.9% of the
      patients had multiple cancers, a careful workup was necessary preoperatively.
      Since most patients (88.9%) had complications and were also in a poor general
      condition, limited surgery was recommended in consideration of the postoperative
      quality of life. The indications for endoscopic mucosal resection (EMR) may be
      able to be extended to submucosal1 (sm1) cancer without lymph node swelling.
      Postoperative complications occurred in 60% of those undergoing surgical
      resection or esophageal bypass, although death only resulted in 1 case. The 5
      year survival rate after surgical resection was 30.8%. These results therefore
      support the use of surgical treatment for selected elderly patients with
      esophageal cancer.

PMID- 9035295
TI  - Surgery for gastric cancer in patients with cirrhosis.
AB  - To clarify the therapeutic strategies for gastric cancer surgery in the presence
      of cirrhosis, 39 patients with gastric cancer accompanied by liver cirrhosis were
      reviewed. Severe postoperative complications developed in 10 patients (25.6%),
      and there were 4 (10.3%) hospital deaths. 1 (2.6%) of which occurred within 1
      month. Although extended lymph node dissection of D2 or more was adopted for low
      risk patients, 3 of 19 patients who underwent such extensive operations, most of
      which involved complete lymph node dissection in the hepatoduodenal ligament,
      died. Conversely, only 1 of 20 patients who underwent limited lymph node
      dissection of D1 or less died. Postoperative massive ascites developed in 6
      patients, 3 of whom died. The cumulative 5-year survival rate following curative
      resection was 63.7% for patients with early gastric cancer, and 13.9% for those
      with advanced gastric cancer. The most frequent cause of death was cirrhosis
      related, such as hepatic failure or hepatoma. In conclusion, extensive lymph node
      dissection for patients with gastric cancer accompanied by cirrhosis carried a
      risk of postoperative fatal massive ascites as lymphorrhea. Thus, lymph node
      dissection in the hepatoduodenal ligament should be avoided, except in patients
      with evident metastases, and as a rule, aggressive surgery should not be
      performed in cirrhotic patients.

PMID- 9035296
TI  - Effect of antileukocyte adhesion molecule antibodies, nitric oxide synthase
      inhibitor, and corticosteroids on endotoxin shock in mice.
AB  - We compared the therapeutic effects of anti-leukocyte adhesion molecule
      antibodies (mAbs), a nitric oxide (NO) synthase inhibitor (monomethyl-L-arginine,
      NMLA), and methylprednisolone (MP) on experimental endotoxin-induced shock in
      mice. Lipopolysaccharide (LPS, 30 mg/kg) was administered to ICR mice
      intraperitoneally, While 1 mg/kg mAb, 5-20 mg/kg NMLA, or 30 mg/kg MP was
      administered intravenously. The placebo group received phosphate-buffered saline.
      The survival rate of the placebo group 48 h after LPS injection was 36%. The
      administration of anti-CD11a, anti-CD18, anti-lectin cell adhesion molecule-1
      (anti-LECAM-1), and MP increased the survival rate to 70, 62, 64, and 100%,
      respectively; however, NMLA had no significant effect. A FACS analysis revealed
      that the CD18 expression of granulocytes increased 12-fold within 30 min after
      LPS administration. MP significantly suppressed its expression. The plasma level
      of nitrate/nitrite increased from 20 to 260 and 1000 microM 4 and 16 h,
      respectively, 20 mg/kg NMLA abolished NO production at 4 h, while MP inhibited it
      for up to 16 h. The hepatic malondialdehyde level increased from 0.50 to 2.46
      nmol/mg protein at 4 h. Administration of anti-CD18 and MP reduced the level to
      1.80 and 1.41 nmol/mg protein, respectively, whereas NMLA did not affect it. The
      mAbs and MP were concluded to be useful agents for endotoxin shock. The abolition
      of NO production had little influence on the hepatic cellular injury associated
      with endotoxemia.

PMID- 9035297
TI  - Enhanced expression of lipocortin-1 as a new immunosuppressive protein in cancer
      patients and its influence on reduced in vitro peripheral blood lymphocyte
      response to mitogens.
AB  - To clarify the mechanism of immunosuppression in cancer-bearing hosts, the
      expression of lipocortin-1 (LC1), a new immunosuppressant, and its effects on the
      in vitro mitogen responsiveness of peripheral blood mononuclear cells (PBMC) were
      investigated in cancer patients. Immunohistochemical studies showed LC1
      expression in the cytoplasm of inflammatory cells morphologically recognized as a
      macrophage lineage, infiltrating the tumor interstices of gastric cancer. LC1
      protein was detected in the ascitic fluid from gastric cancer patients using
      Western blot analysis. LC1 expression in PBMC was studied using a fluorescence
      activated cell sorter (FACScan), which revealed that the percentage of CD14 and
      LC1 double positive cells was much greater in cancer patients than in healthy
      individuals. The proliferative response of PBMC by concanavalin A (ConA)
      stimulation was significantly suppressed in patients with advanced cancer, while
      the intact mitogen responsiveness in healthy individuals was inhibited when
      recombinant LC1 was added to the cultures. A similar inhibitory effect was
      induced by adding the supernatant of cancerous ascites or spleen cell cultures
      derived from advanced cancer patients. These inhibitory effects were eliminated,
      and the suppressed mitogen responsiveness in cancer patients recovered to the
      control level of healthy individuals when anti-LC1 antibody was added to the
      cultures. These findings indicate that LC1 is produced and expressed in cancer
      patients, and deeply involved in the immunosuppressive mechanism of tumor-bearing
      hosts.

PMID- 9035298
TI  - Effect of gene therapy with the herpes simplex virus-thymidine kinase gene on
      hepatic metastasis in murine colon cancer.
AB  - Hepatic metastasis of colon cancer is an important prognostic factor for
      survival. In this study, we examined the effect of gene therapy using the herpes
      simplex virus-thymidine kinase (HS-tk) gene with short-course ganciclovir (GCV)
      treatment for multiple hepatic metastases of murine colon cancer. Colon26 cells
      transfected with the HS-tk gene were found to be sensitive to GCV in a
      concentration-dependent way. On the other hand, induction of the HS-tk gene in
      the cells had no influence on cell growth in vitro. However, multiple hepatic
      metastases of Colon26 cells transfected with HS-tk gene were significantly
      suppressed by the GCV treatment. These results thus suggest that HS-tk gene
      therapy is useful for the treatment of hepatic metastasis in colon cancer.

PMID- 9035299
TI  - The production and clearance of endothelin and its influence on kidney function
      after liver transplantation in rats.
AB  - To assess the involvement of endothelin-1 (ET-1) in rat liver allograft
      rejection, we evaluated ET-1 expression in tissues obtained from BN (RT1n) to BN
      rats (group 1), and DA (RT1a) to BN rats (group 2). The ET-1 levels in group 1,
      determined by radioimmunoassay, remained low in the serum, liver, and bile, but
      in group 2, they peaked on postoperative day (POD) 5 in the liver, kidney, bile,
      and urine, at 344 +/- 31.6 pg/gwet, 306 +/- 97.4 pg/gwet, 1008 +/- 258 pg/day,
      and 156 +/- 45 pg/day, respectively, whereas levels in the serum peaked on POD 7
      at 38.7 +/- 13.1 pg/ml. In the portal vein (PV) ET-1 showed extremely high levels
      without statistical difference between groups 1 and 2, at 93.0 +/- 15.5, and 83.0
      +/- 9.84 pg/ml on POD 7, respectively. However, in the suprahepatic vena cava
      (SHVC) and the abdominal aorta (AO), the ET-1 levels were statistically higher in
      group 2 compared to group 1 (P < 0.01). Immunohistochemical staining showed
      decreased staining of the liver and kidney in group 2 on POD 7. In conclusion,
      increasing levels of ET-1 were released from the liver and kidney during the
      early stage of rejection, resulting in the high ET-1 levels in these tissues,
      which were cleared promptly. However, an increased production of ET-1 was not
      observed in association with the release of ET-1.

PMID- 9035300
TI  - Graft damage after a single lung transplantation for pulmonary hypertension in a
      rat model.
AB  - The hemodynamic effect and degree of damage in grafts of single lung transplants
      for pulmonary hypertension were studied in rats with monocrotaline-induced
      pulmonary hypertension. Inbred male Lewis rats (weight 200-230 g) were divided
      into two groups. Group 1 (control group, n = 16) underwent isogenic left lung
      transplantation, while group 2 (n = 15) received an intravenous administration of
      monocrotaline (80 mg/kg i.v.) and underwent isogenic left single lung
      transplantation 3 week later. Hemodynamic evaluations were performed prior to
      transplantation, at 1 h postoperatively, and on days 3 and 7 after
      transplantation. Mean pulmonary arterial pressure (mPAP) rapidly declined after
      transplantation in group 2, from 39.3 +/- 8.7 mmHg to 18.5 +/- 3.0 mmHg 1 h after
      transplantation, and remained stable on day 7 after transplantation. No
      significant difference in the mPAP between the two groups was observed after
      transplantation. The extravascular lung water volume (ELWV: dry/wet ratio) in the
      right lung of group 2 significantly increased on day 3 (0.86 +/- 0.02) (P <
      0.01), and subsequently decreased to control levels on day 7 (0.83 +/- 0.02).
      There was no significant difference in the ELWV in the grafted lungs between the
      two groups (0.84 +/- 0.03 vs 0.86 +/- 0.04), but there was tendency toward an
      increase in ELWV in group 2 on days 3 and 7. These data thus demonstrated that a
      hemodynamic improvement was obtained by single lung transplantation; however the
      degree of graft damage was remarkable in the pulmonary hypertension group.

PMID- 9035301
TI  - Primary adenocarcinoma of the stomach associated with peripheral
      neurofibromatosis: report of a case.
AB  - A 55-year old man with von Recklinghausen's disease was admitted to our hospital
      for investigation of weight loss, anorexia, and abdominal discomfort. Endoscopy
      findings revealed impairment in the extendability of the stomach by air, and
      barium meal studies showed a well-contracted stomach. On exploratory laparotomy,
      the whole of the stomach was found to be grossly shrunken with thickening of the
      walls suggesting a "linitis plastica" stomach. Histological findings confirmed
      stage III poorly differentiated diffuse infiltrative adenocarcinoma of the
      stomach. This report describes a rare case of "linitis plastica" stomach in a
      patient with peripheral neurofibromatosis (NF-1) indicating that the NF-1
      disorder does not spare an individual from other common neoplastic disorders.

PMID- 9035302
TI  - Small intestinal cancer with extensive lymph node metastases showing complete
      remission by methotrexate/5-fluorouracil sequential therapy: report of a case.
AB  - A case of poorly differentiated adenocarcinoma of the small bowel with extensive
      lymph node metastases is herein presented, which responded to methotrexate/5
      fluorouracil (MTX/5-FU) sequential therapy. The lymph node metastases disappeared
      completely after 10 months of treatment. After recurrence, combination therapy
      with radiation, hyperthermia, and cisplatinum were also effective in reducing the
      degree of nodal swelling while still allowing the patient to maintain her
      accustomed lifestyle for a prolonged period of time. Further multi-institutional
      studies are still needed, however, to fully assess this new therapeutic regimen
      for small bowel cancers.

PMID- 9035303
TI  - Hemangiopericytoma of the sigmoid mesentery: report of a case with
      immunohistochemical findings.
AB  - Hemangiopericytoma has been described in various sites in the body but only
      rarely in the mesocolon. This report describes the clinical course of an 83-year
      old man whose mesosigmoidal tumor (hemangiopericytoma) was resected on 11
      November 1994. Immunostaining was done with the following primary antibodies:
      alpha-actin, vimentin, factor VIII-related antigen, chromogranin, and S-100.
      Staining for factor VIII-related antigen was strongly positive in the endothelial
      cells of the capillaries, but negative in the tumor cells. The tumor cells
      contained immunoreactive vimentin, but demonstrated no alpha-actin, chromogranin,
      or S-100. Since the operation, the patient has been disease-free for 11 months.

PMID- 9035304
TI  - Combined thoracoscopic lung resection and laser ablation for lung cancer with
      pulmonary emphysema: report of a case.
AB  - We report herein the case of the 71-year-old man with lung cancer and pulmonary
      emphysema requiring supplementary oxygen at 21/min by nasal cannula for whom
      thoracoscopic wedge resection of an adenocarcinoma in his left lower lobe was
      successfully performed. During the same procedure, thoracoscopic laser ablation
      of pulmonary bullae was also carried out. There were no postoperative
      complications, and the patient is currently well 12 months following surgery
      without any evidence of local or regional recurrence, or distant metastasis. His
      severe dyspnea on exertion improved, and he no longer requires supplementary
      oxygen.

PMID- 9035305
TI  - Infant cholelithiasis: report of a case.
AB  - Cholelithiasis is an extremely unusual finding in infancy. The following article
      describes the case of a 2-month-old male with a VACTER association who presented
      with persistent and progressive obstructive jaundice and acholic stool due to
      cholelithiasis. Thirty cases under the age of 1, including our case, have
      previously been reported in the Japanese literature. Twenty-eight cases had
      predisposing factors. The calculi were present only in the gallbladder in 18
      cases, in the common bile duct or cystic duct or both in 7 cases, and in the
      gallbladder and common bile duct in 3 cases. Ten cases of stones were radiopaque,
      which thus made the plain abdominal roentgenogram findings very valuable. Nine
      cases underwent operation including cholecystectomy in 3 cases,
      choledocholithotomy in 3 cases, and cholecystolithotomy in 1 case, while the
      procedure was unknown in 2 cases. Recently, the number of reported cases of
      cholelithiasis in infants has gradually increased and today these cases are most
      often diagnosed by ultrasonography, because the examination is easy to perform
      and not invasive.

PMID- 9035306
TI  - Delayed manifestation of aortic stenosis after blunt abdominal trauma: report of
      a case.
AB  - Delayed manifestation of aortic stenosis caused by abdominal blunt trauma is
      rare. We report herein the case of a 67-year-old man who was taken to a nearby
      hospital after being crushed between a heavy truck and a wall. An emergency
      laparotomy was performed, revealing only a mesenteric tear which was repaired. He
      was discharged after an uneventful postoperative course; however, 1 month later
      he began to experience intermittent claudication, and presented to our hospital
      in December 1994, 1 year after the first operation. Angiography and enhanced
      computed tomography (CT) demonstrated infrarenal abdominal aortic dilatation with
      distal stenosis. Both the dilated and stenotic lesions were resected and bypass
      surgery ws performed. Pathologic examination demonstrated that the intima had
      been lacerated circumferentially and everted distally, causing the aortic
      stenosis. To our knowledge, this is the first case of the delayed manifestation
      of traumatic aortic stenosis to be documented in Japan. The etiology of this rare
      complication of blunt trauma is described in this report.

PMID- 9035307
TI  - Mediastinal parathyroid adenoma detected by 99mTc-methoxyisobutylisonitrile:
      report of a case.
AB  - We report herein the case of a 30-year-old man in whom ectopic mediastinal
      parathyroid adenoma was detected by 99mTc-methoxyisobutylisonitrile scintigraphy
      (99mTc-MIBI). The patient presented with a history of recurrent renal stones and
      was diagnosed as having primary hyperparathyroidism due to elevated serum levels
      of calcium and intact parathyroid hormone (i-PTH) levels. On admission, his serum
      calcium value was 12.1 mg/dl and the i-PTH level was 137 pg/ml. Ultrasonography,
      computed tomography (CT), and 201TlCl-99mTcO4- subtraction scintigraphy (Tl-Tc)
      were performed but none of these imaging techniques was able to detect an
      enlarged parathyroid gland. Selective venous sampling revealed that the serum i
      PTH level was highest at 422 pg/ml in the left brachiocephalic vein. Exploration
      of the neck also proved unsuccessful. Finally, we performed 99mTc-MIBI which
      revealed and delineated an enlarged parathyroid gland in the upper mediastinum.
      Tumor extirpation was subsequently performed through a left thoracotomy.
      Pathologically, the tumor was confirmed to be a parathyroid adenoma and the serum
      calcium and i-PTH levels returned to within the normal ranges postoperatively.

PMID- 9035308
TI  - Successful treatment of blunt trauma involving complete laceration of the
      pancreas and duodenum in a 7-year-old child: report of a case.
AB  - The acute onset of peritoneal signs and shock in a 7-year-old boy who had been
      hit in the epigastrium by a log-seesaw mandated surgical treatment. Enhanced
      computed tomography (CT) demonstrated complete laceration of the pancreas as well
      as duodenal injury, and a duodenoduodenostomy with distal pancreaticogastrostomy
      was subsequently performed. Temporary external drainage of the stomach and distal
      pancreas led to an uneventful recovery in the early postoperative period.
      Although the patient's postoperative development was appropriate for his age, the
      orifice of the distal pancreas spontaneously closed 2.5 years following surgery.
      We present this report to stress the fact that every effort should be made to
      preserve the pancreas following abdominal injury in children.

PMID- 9035309
TI  - Left ventricular fibroma in an aged patient: report of a case.
AB  - We report herein the case of a 77-year-old man with a left ventricular tumor
      originating from the papillary muscle of the left ventricular wall, in whom a
      successful tumor resection with mitral valve replacement was performed. The
      pathological diagnosis of the tumor was confirmed as cardiac fibroma. His
      postoperative course was uneventful and he is currently well with no signs of
      recurrence 2 years after surgery.

PMID- 9035310
TI  - Overexpression of bax enhances the radiation sensitivity in human breast cancer
      cells.
AB  - Bax-alpha, a splice variant of bax which promotes apoptosis, is expressed in many
      kinds of untransformed cell lines and breast tissue, whereas only weak or no
      expression could be detected in breast cancer cell lines and malignant breast
      tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression,
      were stably transfected with pCX2neo bax, encoding human bax and neomycin
      resistant genes, and two unique clones (MCF-7/bax-1 and MCF-7/bax-2) were thus
      generated which expressed different levels of bax-alpha. Sensitivity to ionizing
      radiation (IR) was examined and each was more sensitive to IR than the parental
      MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the
      expression level of bax, and IR was found to induce intranucleosomal DNA
      fragmentation in stable transfectant but not in parent cells, thus suggesting
      that this sensitization is due to apoptosis. We suggest that exogenous bax-alpha
      expression might therefore be one of the factors determining cellular
      radiosensitivity in MCF-7 breast cancer cells and may potentially have a
      therapeutic application by enhancing radiation sensitivity in breast cancer
      cells.

PMID- 9035342
TI  - A study of level of lesion, associated malformations and sib occurrence risks in
      spina bifida.
AB  - Neural tube defects remain the most serious common birth defect and, despite
      considerable progress in understanding these malformations, the etiology of most
      cases remains unknown. It has been proposed that the cause may vary with the type
      and location of the malformation but, if these variables are to be studied, a
      rigorous classification of cases is required. This has become more important as
      birth prevalence has fallen, mainly due to prenatal diagnosis and elective
      termination of pregnancy, and future studies will increasingly require
      collaboration between centres. In this study we have combined data from Ottawa,
      Ontario, and Boston, Massachusetts, in an attempt to examine the effect of level
      of spina bifida on sib occurrence rates and the rates of associated
      malformations, and to compare the level of lesion when determined
      radiographically with that recorded on the clinical chart. Malformations appeared
      to be more frequent with thoracic spina bifida and were more often associated
      with additional vertebral anomalies. Significant differences were found between
      the upper level of lesion recorded in the clinical file and that visible
      radiographically. Sib recurrences were too few for statistical comparison, but
      the data suggest a higher rate among sibs and more distant relatives of propositi
      with upper level lesions. There was not evidence to support a greater than
      expected concordance for level of lesion between sibs.

PMID- 9035343
TI  - Effects of 2-methoxyethanol on mouse neurulation.
AB  - The potent developmental toxicant, 2-methoxyethanol (2-ME), elicits exencephaly
      in near-term mouse fetuses following a single maternal treatment early on
      gestation day (gd) 8. Deleterious morphological consequences to the neurulating
      embryo shortly after exposure have not been reported. The present study was
      designed to fill this gap and to investigate the impact of 2-ME treatment on cell
      death patterns in the embryonic neural folds. Dams were injected subcutaneously
      with saline, 250 or 325 mg 2-ME/kg 2 hr prior to the beginning of gd 8. The
      effect of 2-ME on gross and microscopic neural development was examined in
      conceptuses on gd 9, 6 hr (9:6), 10:6, and 18:0. Compared to saline, 2-ME
      treatment increased the percentage of embryos with open neural tubes (ONTs) at
      all gestation days. Although few statistically significant differences (P < 0.05)
      existed among the ONT rates on the 3 observation days, an interesting biological
      response occurred. Both high and low 2-ME doses appeared to elicit the greatest
      incidence of neural tube patency on gd 9:6 (affecting approximately 27% of
      embryos). During the subsequent 24 hr, recovery occurred and many neural folds
      apparently closed. Consequently, the ONT incidences on gd 10:6 (approximately
      11%) were quite similar to the gd 18 exencephaly rates elicited by both chemical
      treatments (approximately 15%). A dose response was not seen due to a substantial
      increase in resorption rates following the 325 mg/kg dose. Compared to the other
      treatment groups, the low 2-ME dose significantly inhibited embryonic growth as
      indicated by reduced crown-rump and head lengths and increased incidence of
      developmentally delayed brain maturation. To evaluate chemically induced changes
      in cell death, neurulating embryos were collected on gd 8:6 and either immersed
      in the vital dye, Nile blue sulfate (NBS), or processed for histopathology. In 2
      ME-exposed embryos, excessive NBS uptake occurred in neural fold neuroepithelium
      at sites of nonclosure. Using histopathology, the extent of cell death in the
      cephalic neural folds was dependent on the 2-ME dose, and the neuroepithelium was
      more severely affected than the mesenchyme. These observations suggest 1) a trend
      toward repair and catch-up growth later in gestation which may ameliorate the
      overt early effects of 2-ME, and 2) an association between enhanced cell death
      and regions of the neural tube particularly vulnerable to nonclosure.

PMID- 9035344
TI  - Exencephaly and cleft cerebellum in SELH/Bc mouse embryos are alternative
      developmental consequences of the same underlying genetic defect.
AB  - SELH/Bc inbred mice have ataxia in 5-10% of young adults and exencephaly in 10
      20% of newborns. SELH/Bc mice also have a high rate of spontaneous mutation and
      therefore it could not be assumed that these two abnormalities share the same
      genetic cause. Previously, we have shown that the liability to exencephaly in
      SELH/Bc mice is multifactorial, involving two to three loci, and that all the
      ataxics have a midline cleft cerebellum. The purpose of the present study was to
      resolve the genetic relationship between liability to exencephaly and liability
      to cleft cerebellum. We tested whether these traits were transmitted together by
      segregating F2 males; cotransmission would indicate that both traits are probably
      caused by the same genes. Approximately 100 embryos from each of 25 F2 sires from
      a cross between SELH/Bc and the normal LM/Bc strain were scored for exencephaly
      and the non-exencephalic embryos were scored for cleft cerebellum. The range of
      exencephaly production by these 25 F2 sires was 0% to 16%; the sires had been
      selected to represent the extremes of the range of exencephaly production. We
      found that the 10 sires that produced no exencephaly also produced no cleft
      cerebellum and 12 of the 15 sires that produced some exencephaly also produced
      some cleft cerebellum. This indicated strongly that the two traits are
      transmitted together (Fisher's exact test, P < 0.0002). Furthermore, within
      exencephaly-producing sires, the specific frequencies of the two traits were
      significantly positively correlated (Spearman rs = 0.58; P < 0.05), indicating
      that the same multifactorial risk factors influence both traits. All SELH/Bc
      embryos omit one normal initiation site of cranial neural tube closure, Closure
      2. In a previous study, absence of the Closure 2 initiation site of cranial
      neural tube closure has been shown to be genetically correlated with liability to
      exencephaly. In the second part of the present study, the same Closure 2 data
      from eight of the F2 sires were observed to be significantly positively
      correlated with liability to cleft cerebellum (Spearman rs = 0.83; P < 0.05). The
      results of this genetic approach have supported the hypothesis, based on
      observation of embryos, that one basic multifactorial genetic defect in SELH mice
      leads to an abnormal cranial neural tube closure mechanism, to exencephaly to
      cleft cerebellum, and to ataxia.

PMID- 9035345
TI  - Histological changes in rat embryonic blood cells as a possible mechanism for
      ventricular septal defects produced by an N-phenylimide herbicide.
AB  - An N-phenylimide herbicide, S-53482, inhibits protoporphyrinogen oxidase, an
      enzyme common to chlorophyll and heme biosynthesis, and produces embryolethality,
      teratogenicity [mainly ventricular septal defects (VSD) and wavy ribs], and
      growth retardation in rats. In order to elucidate the mechanism of the
      developmental toxicity, in particular VSD, effects of the herbicide on rat
      embryonic blood cells were investigated histologically at the light and electron
      microscopic levels at 6, 12, 24, 36, and 48 h after oral administration of the
      chemical to pregnant rats on day 12 of gestation, the most sensitive day for
      toxicity. Electron and light microscopy demonstrated mitochondrial lesions,
      including abnormal iron deposits that were probably due to inhibition of heme
      biosynthesis, in erythroblasts derived from the yolk sac. Subsequently,
      degeneration of these erythroblasts occurred followed by erythrophagocytosis.
      Histologically hearts from exposed embryos had a thin ventricular wall, which may
      reflect a compensatory reaction to a loss of embryonic blood cells. Thus, the
      herbicide may induce VSD due to hematological dysfunction caused by the
      inhibition of heme biosynthesis rather than by direct injurious effects on the
      heart.

PMID- 9035346
TI  - Ethanol in utero induces epithelial cell damage and altered kinetics in the
      developing rat intestine.
AB  - The effect of prenatal ethanol exposure on the intestinal maturation of rat
      fetuses was investigated to understand the nutritional alterations found in the
      offspring of alcoholic mothers. Female Wistar rats were maintained on solid diet
      and 25% ethanol solution as drinking fluid during pregnancy, and non-alcoholic
      isocaloric pregnant mothers were used as controls. At birth, intestines from
      unsuckled pups were removed for study. The weight and length of the intestine
      decreased significantly when ethanol was present in utero. Ultrastructural
      evaluation of the epithelium revealed loss of contact between neighboring
      enterocytes and abnormal dilation of the cisternae of the Golgi apparatus in
      ethanol-exposed pups. Further, increased lysosome-like vesiculation and enhanced
      lysosomal beta-galactosidase activity was observed in these neonates. The total
      number of absorptive enterocytes in the epithelium was reduced by 30% in ethanol
      exposed neonates as compared to controls, due to altered cell growth and death
      during fetal life. Ethanol in utero stimulated epithelial cell migration which
      compensated cell loss, as demonstrated by 5'-Bromodeoxyuridine labeling. These
      findings could have important implications for the assimilation of nutrients and
      failure to thrive in infants with fetal alcohol syndrome.

PMID- 9035348
TI  - Effects of hypoglycemia on mouse embryos in vitro are not the same as those of
      hypoglycemia on embryos in pregnant diabetic women.

PMID- 9035347
TI  - Retinoid metabolism and transplacental pharmacokinetics in the cynomolgus monkey
      following a nonteratogenic dosing regimen with all-trans-retinoic acid.
AB  - Retinoids often exhibit a complex metabolic pattern and differential
      transplacental kinetics, which make it difficult to pinpoint the proximate
      compound responsible for the observed teratogenic effect. We have therefore
      studied the pharmacokinetics and metabolism of all-trans-retinoic acid (all-trans
      RA) in cynomolgus monkeys following application of a nonteratogenic dosing
      regimen and compared the results with corresponding data from a previous study
      with a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994)
      Teratology 50:184-193]. All-trans-RA was administered to pregnant cynomolgus
      monkeys (Macaca fascicularis) by nasogastric intubation at a dose of 5 mg/kg body
      wt once daily from gestational day (GD) 16 to 26 and twice daily at 8-h intervals
      from GD 27 to 31. Examination of the fetuses of four dams on GD 100 +/- 2 showed
      no embryotoxic or teratogenic effects of the applied dosing regimen (Experiment
      1). Maternal plasma retinoid pharmacokinetics on GD 16, 26, and 31 as well as
      embryonic retinoid profiles after the last drug administration on GD 31 were
      determined in thirteen further dams (Experiment 2). All-trans-RA reached much
      lower plasma concentrations after the last two treatments on GD 31 than after the
      first one on GD 16 and the eleventh one on GD 26 (0-24-h area-under-the
      concentration-time-curve (AUC) values: 104 +/- 59 ng x h/ml (after the last
      treatment on GD 31), 189 +/- 110 (GD 16) and 393 +/- 305 ng x h/ml (GD 26). The
      predominant plasma metabolites of all-trans-RA were its beta-glucuronide and the
      beta-glucuronide of all-trans-4-oxo-RA. Both of these retinoids accumulated in
      the plasma during the period of treatment and displayed AUC values 5- to 30-fold
      higher than those of all-trans-RA. Embryonic concentrations of all-trans-RA were
      not increased over endogenous levels after the last administration on GD 31 when
      plasma concentrations were low. To evaluate the placental transport of all-trans
      RA in the presence of high plasma concentrations, a further experiment was
      performed, in which a single dose of all-trans-RA (10 mg/kg body wt) was given to
      four pregnant monkeys on GD 31, and plasma pharmacokinetics as well as embryonic
      concentrations of retinoids at 4 h post-treatment were determined (Experiment 3).
      This dosing schedule yielded high plasma concentrations of all-trans-RA, while
      embryonic concentrations were about 40% of plasma levels. Based on the plasma AUC
      values on GDs 16 and 26 obtained in Experiment 2 and the degree of placental
      transfer, as determined on GD 31 in the presence of high plasma levels in
      Experiment 3, we estimated embryonic AUC values for the 24-h period following the
      nonteratogenic doses on GDs 16 and 26 in Experiment 2. These AUC values were
      similarly high to the embryonic AUC value of all-trans-RA obtained after
      application of the teratogenic dosing regimen with 13-cis-RA [Hummler et al.
      (1994) Teratology 50:184-193]. In addition, plasma AUC values of all-trans-RA
      were 2- to 7-fold higher after all-trans-RA administration (present study) than
      after dosing with the teratogenic dose of 13-cis-RA. These results strengthen our
      recent suggestion that the teratogenic effects induced in cynomolgus monkeys by
      13-cis-RA treatment cannot solely result from the action of all-trans-RA, but may
      involve 13-cis-RA and 13-cis-4-oxo-RA, which could act directly or function as
      transport vehicle.

PMID- 9035349
TI  - Diversification is the future for many tobacco farmers.

PMID- 9035350
TI  - Civil disobedience and tobacco control: the case of BUGA UP. Billboard Utilising
      Graffitists Against Unhealthy Promotions.

PMID- 9035351
TI  - USA: tobacco is a drug--official.

PMID- 9035352
TI  - Shaming big tobacco's friends in California.

PMID- 9035353
TI  - Tobacco farmers and diversification: opportunities and barriers.
AB  - OBJECTIVE: To assess the knowledge, attitudes, and behaviours of tobacco growers
      and allotment owners in the southeastern United States. DESIGN: Cross-sectional
      telephone survey. PARTICIPANTS: Tobacco growers (n = 529) and tobacco allotment
      owners (n = 417) were interviewed by telephone in March 1995. SETTING: Tobacco
      growing states in the southeastern US. MAIN OUTCOME MEASURES: Attitudes of
      tobacco growers and tobacco allotment owners towards, and experience with,
      diversification; and attitudes towards an increase in the federal excise tax on
      tobacco. RESULTS: Half of the respondents had done something to learn about on
      farm alternatives to tobacco, had an interest in trying other on-farm ventures to
      supplement tobacco income, and found alternatives that were profitable. There was
      a strong, negative linear trend between age and being interested in or trying
      alternative enterprises. Structural and economic impediments to diversification
      were noted by respondents (especially younger respondents), but 73% supported an
      increase in the federal excise tax on tobacco if the money was used to help
      farmers overcome these barriers. CONCLUSIONS: These data suggest that farmers and
      health professionals have reason to establish dialogue around diversification and
      using excise tax increases to fund diversification and to promote health. Tobacco
      companies have been successful in mobilising farmers against tax increases, but
      efforts must be made to show farmers that tax increases can be beneficial both to
      their diversification efforts and to public health. The outcome of this dialogue
      may well affect the economic infrastructure of thousands of rural communities,
      the livelihood of tens of thousands of tobacco farmers and their families, and
      the health of millions of tobacco users.

PMID- 9035354
TI  - Smoking on hospital grounds and the impact of outdoor smoke-free zones.
AB  - OBJECTIVES: To describe the type and location of smokers on the grounds of smoke
      free public hospitals and to observe the impact of introducing smoke-free signs
      in outdoor areas of the hospital grounds. DESIGN: Observation study of outdoor
      smoking behaviour before and after the introduction of outdoor smoke-free signs
      at one hospital (H1) and at the same two time periods at a nearby control
      hospital (H2), which already had some outdoor smoke-free signs at Time 1.
      SETTING: The John Hunter Hospital (H1) in Newcastle, Australia and a nearby
      control hospital, Maitland Hospital (H2) in 1991. SUBJECTS: All people in defined
      outdoor sites of the two hospitals on seven randomly selected days over two weeks
      before and after the policy change were coded as either "smoker" or "non-smoker"
      and as either "staff", "patient", or "visitor". The number of smokers observed in
      each site was measured as a proportion of all smokers observed on the grounds of
      that hospital. INTERVENTION: Introduction of outdoor smoke-free zones and signs
      at H1. RESULTS: Less than 10% of observed outdoor smokers in both hospitals were
      patients, 40% were visitors, and more than 50% were staff. Of outdoor smokers,
      82% were observed less than 10 m from entrances to the hospital building at time
      1. After the introduction of signs in H1, a 4-percentage point decrease (P <
      0.05) occurred in the percentage of smokers observed in smoke-free zones at time
      2 (from 32% to 28%), compared with a 2-percentage point decrease (P > 0.05 at
      time 2 in H2 (from 48% to 46%). DISCUSSION: This observation study of smoking
      behaviour in hospital grounds highlights the need to reduce smoking among staff
      and visitors near hospital entrances. Specific strategies are discussed, which
      are likely to enhance compliance and hence enable the effective introduction of
      smoke-free policies on hospital grounds.

PMID- 9035355
TI  - Trends in prevalence and acceptance of workplace smoking bans among indoor
      workers in South Australia.
AB  - OBJECTIVE: To compare the reported prevalence and acceptance of bans on smoking
      in the workplaces of a representative sample of adults in South Australia between
      1989 and 1994. DESIGN: Independent cross-sectional representative population
      surveys. SETTING: South Australian population. PARTICIPANTS: Adults who indicated
      they were employed mainly indoors, for the years 1989 (875 respondents), 1991
      (1472), 1992 (1288) and 1994 (1273). MAIN OUTCOME MEASURES: Percentage reporting
      total bans on smoking at work; percentage reporting compliance with bans all or
      nearly all the time; percentage reporting preference for total bans at work.
      RESULTS: The percentage of indoor workers subject to a total ban on smoking at
      work increased from 32% in 1989 to 62% in 1994 and preference for a total ban
      increased during the same period from 26% to 52%. Reported compliance with
      restrictions and bans was very high. In 1994, 16% of workers still had no
      restrictions on smoking at work, but only 3% preferred this arrangement.
      CONCLUSION: The data suggest that smoking bans are now the norm for indoor
      workers and that further gains in promoting and supporting workplace bans will be
      made by directing efforts at smaller workplaces, where unrestricted smoking is
      most prevalent.

PMID- 9035356
TI  - Quitting smoking: why, how, and what might help.
AB  - OBJECTIVE: To examine reasons for quitting smoking, methods used in quitting,
      reasons for continuing smoking and potential aids to quitting in the population
      of Ontario, Canada. DESIGN: Two population-based, telephone interview surveys,
      conducted by random-digit dialing. SUBJECTS: Adults aged 18 years of age and
      older in 1983 (n = 1383) and 1991 (n = 1421). MAIN OUTCOME MEASURES: Information
      was obtained from former smokers on why and how they quit smoking, and from
      continuing smokers on why they smoked and what might help them quit. RESULTS: The
      proportion of current smokers in the population decreased from 35.5% in 1983 to
      27.2% in 1991. In both surveys, former smokers cited a variety of reasons for
      quitting, including personal health concerns, social and environmental factors,
      personal attitude factors, cost, and health education messages. Responses
      concerning the most important reason also revealed a range of factors; "advice of
      a physician" was not prominent among them. When questioned about methods used in
      quitting, most former smokers in both surveys responded that they "just decided
      to quit". Very few reported using other aids such as cessation clinics or
      nicotine gum. More smokers in 1991 than in 1983 reported that they continued
      smoking for enjoyment, to satisfy a craving or addiction, and for relaxation.
      With regard to what might help them quit, continuing smokers in both surveys
      cited a wide variety of potential aids, including information on harmful effects,
      more restrictions on smoking and on sales, cessation clinics, programmes on
      radio/TV, and higher taxes. CONCLUSIONS: These findings support a multifaceted
      approach to tobacco control.

PMID- 9035357
TI  - Smoking behaviour and attitudes among adult Saudi nationals in Riyadh City, Saudi
      Arabia.
AB  - OBJECTIVE: To measure the smoking behaviour and attitudes among Saudi adults
      residing in Riyadh City, the capital of the Kingdom of Saudi Arabia. DESIGN:
      Cross-sectional survey. SETTING AND SUBJECTS: Primary health care centres (PHCCs)
      in Riyadh City were selected by stratified random sampling. Subjects resident in
      each PHCC catchment area were selected by systematic sampling from their records
      in the PHCCs; 1534 adults aged 15 years and older were interviewed during January
      to April 1994. MAIN OUTCOME MEASURES: Self-reported smoking prevalence; age of
      smoking initiation; daily cigarette consumption; duration of smoking; reasons for
      smoking, not smoking, and quitting smoking; intentions to smoke in the future;
      and attitudes toward various tobacco control measures. RESULTS: 25.3% of
      respondents were current smokers, 10.2% were ex-smokers, and 64.5% had never
      smoked. About 79% of all smokers started smoking between the ages of 15 and 30
      years, and 19.5% before age 15. Significantly higher smoking prevalence and daily
      cigarette consumption were associated with being male, single, and being more
      highly educated. Relief of psychological tension, boredom, and imitating others
      were the most important reasons for smoking, whereas health and religious
      considerations were the most important reasons for not smoking among never
      smokers, for quitting among ex-smokers, and for attempting to quit or thinking
      about quitting among current smokers. About 90% of all subjects thought that they
      would not smoke in the future. Physicians and religious men were identified as
      the most effective anti-smoking advocates by a much higher proportion of
      respondents (44%) than nurses, health educators, and teachers (each less than
      5%). Health and religious education were generally cited as more effective in
      deterring smoking than tobacco control laws and policies. CONCLUSIONS: Cigarette
      smoking is prevalent among Saudi adults in Riyadh, particularly males, most of
      whom begin to smoke rather early in life and continue for many years. Health and
      religious education should be the cornerstone for any organised tobacco control
      activities, which are urgently needed to combat the expected future epidemic of
      smoking-related health problems.

PMID- 9035358
TI  - An analysis of the successful 1992 Massachusetts tobacco tax initiative.
AB  - In November 1992, voters in Massachusetts (United States) passed a statewide tax
      initiative adding an extra 25 cents to the price of a pack of cigarettes. The
      Massachusetts Coalition for a Healthy Future, led by volunteers from the
      Massachusetts Division of the American Cancer Society, achieved this victory,
      despite a public anti-tax mood and $7.3 million spent by the tobacco industry.
      The tax has since generated millions of dollars for tobacco education and control
      programmes, leading to acceleration of the decline of tobacco consumption in the
      state. An analysis of the passage of this initiative should help other states
      considering this approach to tobacco control.

PMID- 9035359
TI  - One-year follow up of college student occasional smokers.

PMID- 9035360
TI  - Smoking prevalence in younger Italians.

PMID- 9035361
TI  - FDA regulations restricting the sale and distribution of cigarettes and smokeless
      tobacco to protect children and adolescents (executive summary).

PMID- 9035362
TI  - Comparison of the nucleotide sequence of the coat protein open reading frame of
      nine isolates of wheat streak mosaic rymovirus.
AB  - Wheat streak mosaic rymovirus (WSMV) is an important pathogen of wheat (Triticum
      aestivum L.). The coat protein region of nine isolates of WSMV were cloned by RT
      PCR using primers that were inclusive of nucleotides 398-1825 (1) and sequence
      analysis indicated four regions of variability among the isolates.

PMID- 9035363
TI  - Computer simulations of proteolysis of Marburg and Ebola-Zaire filovirus coded
      proteins to generate nonapeptides with motifs of known HLA class I haplotypes and
      detection of antigenic domains in the viral glycoproteins.
AB  - The primary amino acid sequences of the proteins coded by Marburg and Ebola-Zaire
      filoviruses were studied by computer programs to search for putative proteolytic
      cleavages which yield nonapeptides with motifs of binding to known HLA class I
      haplotypes. The computer analyses predicted that numerous nonapeptides with
      motifs to bind HLA class I A68 and A2 haplotypes were detected. A few
      nonapeptides with motifs HLA class I A24, B8, B27 and B35 were predicted in
      Marburg virus proteins. A similar finding is reported for Ebola-Zaire viral
      proteins (the viral polymerase was not studied). The search for antigenic domains
      that may induce the humoral immune response in the viral glycoproteins was based
      on computer analyses of the physical properties and antigenicity predictions of
      amino acids in certain domains of the primary amino acid sequences. Twelve
      putative antigenic domains were detected in Marburg virus glycoprotein and 11
      putative antigenic domains in Ebola-Zaire virus glycoprotein. Despite the marked
      differences in the primary amino acid sequences in the putative antigenic domains
      of the two viral glycoproteins, 8 antigenic domains were found to have similar
      locations in the viral glycoproteins of the two viruses. Each pair of antigenic
      domains resemble each other in the physical properties of the amino acids that
      are different. These computer analyses may provide an approach to developing
      synthetic peptides capable of induction of both the cellular and humoral
      responses to protect against infection with Marburg or Ebola viruses.

PMID- 9035364
TI  - Tyrosine phosphorylation of measles virus P-phosphoprotein in persistently
      infected neuroblastoma cells.
AB  - Replication and encapsidation of measles virus (MV) requires the interaction
      between the nuclear protein (N) and the phosphoprotein (P). It is known that both
      proteins are phosphorylated on serine and threonine residues. Recently we have
      shown that N is phosphorylated on tyrosine in persistently-infected mouse
      neuroblastoma cells (NS20Y/MS). Here, we show that P in NS20Y/MS is also
      phosphorylated on tyrosine. To investigate whether cellular tyrosine kinases can
      bind and phosphorylate P, a solid phase kinase assay was employed. We show that
      bacterially-expressed MV P fragments, were phosphorylated on tyrosine by purified
      mouse c-Src protein-tyrosine kinase and when mixed with uninfected neuroblastoma
      cell (NS20Y) extracts, these P fragments were phosphorylated on tyrosine in
      addition to serine and threonine. These results imply that MV P is a substrate
      for tyrosine phosphorylation by cellular tyrosine kinase(s).

PMID- 9035365
TI  - "Hairpin" and "hammerhead" ribozymes directed towards the mumps virus
      nucleocapsid RNA: specific cleavage of a small synthetic RNA substrate and full
      length mRNA.
AB  - In an attempt to develop efficient antiviral agents against Mumps virus, we
      designed ribozymes targeting the nucleocapsid (NP) mRNA. Transacting catalytic
      RNAs of the hammerhead and hairpin types were synthesized; they contained
      specific motifs, shared similar flanking regions and were directed against a
      5'GUC3' target immediately downstream to the initiation codon of NP mRNA. Both
      ribozymes were first assayed on a synthetic 16 bases target RNA and found to
      catalytically and efficiently cleave the substrate in a sequence specific way. No
      cleavage, however, occurred when mutated forms of the ribozymes were used. In
      addition, both ribozyme types, when tested on the full length NP mRNA, were also
      able to cleave the substrate although turnover could not be demonstrated. As a
      rule, the hammerhead ribozyme proved more efficient than its hairpin counterpart,
      as well on the synthetic RNA substrate as on the full length NP mRNA target.

PMID- 9035366
TI  - Two mutations in gB-1 and gD-1 of herpes simplex virus type 1 are involved in the
      "fusion from without" phenotype in different cell types.
AB  - Previous studies have shown that certain strains of herpes simplex viruses type 1
      (HSV-1) are able to induce "fusion from without" (FFWO) which means no
      transcription or translation of the viral genome happens. The main determinants
      for FFWO in BHK cells are mutations in the C-terminal part of gB-1. But single
      mutations in this part of the genome are not sufficient to transfer the FFWO
      phenotype also to Vero cells. Here, we report that FFWO of HSV strains indeed
      need additional mutations in the N-terminal part of gD in order to produce the
      FFWO phenotype in BHK and Vero cells. By marker transfer we are able to show that
      loss of mutations in the N-terminal part of gD influences the ability to induce
      FFWO in Vero cells but not in BHK cells. We assume that a mutated gD allows the
      entrance of a multiple number of virus particles into the cell and enhances
      therefore the fusion activity of the mutated gB. Mutations in gD alone are not
      sufficient for fusion activity of HSV.

PMID- 9035367
TI  - The putative LEF-1 proteins from two distinct Choristoneura fumiferana multiple
      nucleopolyhedroviruses share domain homology to eukaryotic primases.
AB  - We have identified the lef-1 genes from two multiple nucleopolyhedroviruses that
      infect natural populations of Choristoneura fumiferana. The lef-1 genes in both
      viruses are directly upstream and in the opposite orientation of their respective
      ecdysteroid UDP-glucosyltransferase (egt) genes. This gene organization pattern
      is similar to that found in the genomes of AcMNPV and of OpMNPV. As well, the
      coding regions and putative protein sequences share a high degree of similarity.
      Alignment of the predicted amino acid sequences of all known baculovirus lef-1
      genes suggests that the LEF-1 proteins have a relatively high degree of
      conservation, particularly at four identified and distinct domains. Moreover, LEF
      1 proteins bear clear similarity to some eukaryotic primases, predominately at
      three of the four domains where certain amino acids are absolutely conserved.

PMID- 9035368
TI  - Rice tungro spherical virus: nucleotide sequence of the 3' genomic half and
      studies on the two small 3' open reading frames.
AB  - Rice tungro spherical virus (RTSV) consists of a single-stranded RNA genome of
      about 12 kilobases that contains one large open reading frame, ORF 1 and two
      small ORFs 2 and 3 at its 3' end (Shen et al., 1993, Virology 193:621-630); it
      was suggested that ORF 2 was expressed via a frameshift. To study the genomic
      information of RTSV and the variation between different RTSV isolates, the 3'
      half of a Philippine isolate and parts of a Thai and an Indian isolate were
      cloned and sequenced. Significant sequence differences were found in ORF 2 and in
      the 3' non-translated region. Additional stop codons have been revealed in the
      previously described ORF 2 in several independent clones from the three different
      virus isolates, the most conserved stop codon in the middle of ORF 2 being
      confirmed by direct RNA sequencing. These results suggest that ORF 2 could only
      express a peptide of about 5 kDa instead of 12 kDa as proposed earlier.
      Polyclonal antisera were raised against ORF 2 and 3 proteins as fusions with
      glutathione-S-transferase. Using these antisera we failed to detect any virus
      specific peptides in extracts from infected rice plants and in virus
      preparations. The nucleotide sequence of the 3' end of our RTSV isolates contains
      several small ORFs and does not contain a repeat of 256 nucleotides found in the
      published sequence. These results indicate that RTSV could contain an unusually
      long 3' non-coding region of 1240 nucleotides in length.

PMID- 9035369
TI  - Computational characterisation of potential RNA-binding sites in arenavirus
      nucleocapsid proteins.
AB  - A nucleocapsid protein of an RNA virus was characterised using computational
      methods. Similarity searches using standard algorithms and more sensitive methods
      based on profiles were performed. Also, secondary structure prediction and
      statistical methods were used. The results show that the protein belongs to a
      unique well-characterised family, with three regions with potential RNA binding
      capacity. The amino-terminal region is found to contain a mixed-charge segment
      similar to proteins that bear nucleic acid-protein interaction capacity. The
      middle-region has a slight homology to the nucleolar protein Fibrillarin
      containing an atypical RNP-1 conserved octamer. Finally, the carboxyl-terminal
      region has a putative zinc-finger.

PMID- 9035370
TI  - Clustering of Argentinean tospoviruses with existing species in the genus by
      sequence analysis of a 450-nucleotide RNA region of the N gene.
AB  - The genomic diversity of Argentine Tospoviruses from different geographical
      areas, and from several distinct crops was analysed here. For each isolate, RT
      PCR, cloning and sequencing of a 450 nt fragment of the N gene were performed.
      Comparisons of RNA and predicted amino acid sequence identity and similarity were
      made. A partial sequence of the N gene was able to classify our local isolates
      within three Tospovirus species previously described (Tomato spotted wilt virus,
      TSWV; tomato chlorotic spot virus, TCSV and groundnut ringspot virus, GRSV). With
      the sequence data currently available, we performed a cladistic phylogenetic
      analysis which gave a possible genealogy among members of the Tospovirus genus.

PMID- 9035371
TI  - Bovine herpesvirus 1 isolates contain variable copy numbers of GC-rich tandem
      repeats in the gI non-coding regions of their genomes.
AB  - A polymerase chain reaction (PCR) targeted to the central portion of the bovine
      herpesvirus 1 (BHV1) genome, and overlapping the 3' untranslated end of the gI
      glycoprotein, was used to amplify BHV1 genomic sequences. PCR products generated
      from cell cultures infected with BHV1.1 were consistently smaller than the
      corresponding products from cells infected with BHV1.2. The nature of the
      sequence differences between these isolates within the target region was found to
      be a consequence of variable numbers of small GC rich repeats, particularly the
      sequence 5'-G(A/T)CC-3', present in the region downstream of the gI coding
      region. Based on these differences a modified PCR protocol which readily
      discriminated between several BHV1.1 and BHV1.2 strains was devised.

PMID- 9035372
TI  - Acquisition of the ts phenotype by a chemically mutagenized cold-passaged human
      respiratory syncytial virus vaccine candidate results from the acquisition of a
      single mutation in the polymerase (L) gene.
AB  - A cold-passaged (cp) temperature-sensitive (ts) mutant of human respiratory
      syncytial virus designated RSV cpts-248 was previously derived by random chemical
      mutagenesis of the non-ts mutant cp-RSV that possesses one or more host range
      mutations. We previously demonstrated in rodents and seronegative chimpanzees
      that the cpts-248 virus is more attenuated than cp-RSV and is more stable
      genetically than previously isolated RSV ts mutants. In the present study, we
      determined that the acquisition of the ts phenotype and the increased attenuation
      of the cpts-248 virus are associated with a single nucleotide substitution at
      nucleotide 10,989 that results in a change in the coding region (amino acid
      position 831) of the polymerase gene. The identification of this attenuating ts
      mutation is important because cpts-248 was used as the parent virus for the
      generation of a number of further attenuated mutants that are currently being
      evaluated as candidate vaccine strains in clinical trials in infants.
      Furthermore, technology now exists to rationally design new vaccine candidates by
      incorporating multiple attenuating mutations, such as the one identified here,
      into infectious viruses that are genetically stable and appropriately attenuated.

PMID- 9035374
TI  - Double-mode impedance analysis of epithelial cell monolayers cultured on shear
      wave resonators.
AB  - The viscoelastic behavior of epithelial cells (MDCK-I and MDCK-II) grown on AT
      cut quartz crystals with a fundamental resonance at 5 MHz was investigated by
      impedance spectroscopy. Using the electromechanical model recently derived by
      Martin et al. [(1991) Anal Chem 63: 2272-2281] for Newtonian liquids in contact
      with shear wave resonators we quantified the viscous damping arising from the
      adherent cells by fitting the impedance data with a modified Butterworth-Van Dyke
      circuit in the region of the resonance frequency. Impedance spectroscopy was
      additionally performed in the frequency range from 1 Hz to 1 MHz to scrutinize
      the passive electrical properties of the epithelial cell layers using an
      additional platinum electrode. These data allow one to document the cell layers'
      integrity as well as the electrode coverage. We were able to confirm that the
      presence of a cell-layer mainly increases damping of the shear wave and does not
      exhibit a pure mass-load behavior. These findings were supported by the discovery
      that the inductance L in the electromechanical model was less influenced by the
      cell-layer than the resistance R. The apparent cell-viscosities determined by our
      method are 0.097 poise for MDCK-I and 0.142 poise for MDCK-II cell-layers. These
      low apparent viscosities may be explained in terms of a considerable spacing
      between the cells immobilized via their focal contacts and the quartz surface.

PMID- 9035375
TI  - Synthesis and cholinesterase inhibitory activity of 6-, 7-methoxy-(and hydroxy-)
      tacrine derivatives.
AB  - Some 6- and 7-methoxy-(and hydroxy-) tacrine derivatives were synthesized and
      evaluated for their in vitro acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE) inhibitory activities. The most potent analogue in
      our series was the 9-heptylamino-6-methoxytacrine 3af which, in comparison with
      tacrine (THA), displayed an almost identical inhibitory effect, slightly lower
      acute toxicity and higher selectivity profile towards AchE when compared with
      THA.

PMID- 9035373
TI  - Pore properties of rat brain II sodium channels mutated in the selectivity filter
      domain.
AB  - Ion selectivity of voltage-activated sodium channels is determined by amino-acid
      residues in the pore regions of all four homologous repeats. The major
      determinants are the residues DEKA (for repeats I-IV) which form a putative ring
      structure in the pore; the homologous structure in Ca-channels consists of EEEE.
      By combining site-directed mutagenesis of a non-inactivating form of the rat
      brain sodium channel II with electrophysiological methods, we attempted to
      quantify the importance of charge, size, and side-chain position of the amino
      acid residues within this ring structure on channel properties such as monovalent
      cation selectivity, single-channel conductance, permeation and selectivity of
      divalent cations, and channel block by extracellular Ca2+ and tetrodotoxin (TTX).
      In all mutant channels tested, even those with the same net charge in the ring
      structure as the wild type, the selectivity for Na+ and Li+ over K+, Rb+, Cs+,
      and NH4+ was significantly reduced. The changes in charge did not correlate in a
      simple fashion with the single-channel conductances. Permeation of divalent ions
      (Ca2+, Ba2+, Sr2+, Mg2+, Mn2+) was introduced by some of the mutations. The IC50
      values for the Ca2- block of Na+ currents decreased exponentially with increasing
      net negative charge of the selectivity ring. The sensitivity towards channel
      block by TTX was reduced in all investigated mutants. Mutations in repeat IV are
      an exception as they caused smaller effects on all investigated channel
      properties compared with the other repeats.

PMID- 9035376
TI  - Beta-adrenoreceptor blocking heterocyclic oximes and ethers.
AB  - This paper reports synthesis and pharmacological properties of thienyl, pyrrol,
      indolyl and benzofuryl-O-(3-alkylamine-2-hydroxypropyl)oximes and some 3-(3
      alkylamine-2-hydroxypropyl)alkyloxy indoles aiming to study the influence of five
      membered and condensed heterocyclic substituents on the beta-adrenoreceptor
      inhibiting potency. All heterocyclic derivatives synthesized (1-17) were less
      active than the reference propranolol on the rat heart, while showed a comparable
      potency on the guinea pig trachea, exhibiting a significant beta 2-selectivity.
      The low beta-blocking potency of the five membered derivatives seemed to confirm
      the negative influence of the polarization of the oximic carbon in the binding
      with non polar region of the beta-adrenoreceptor. Another important interaction
      could take place with the enzyme adenyl-cyclase which is responsible of the
      signal of transduction. It could be hypothesized that the heteroatom of the
      heterocyclic nucleus acted as an electron-donor group and engaged a coordinative
      bond with magnesium atom present on the adenylcyclase system, responsible of the
      agonist activity. The pharmacological in vivo experiments and the binding results
      were in accordance with the in vitro data.

PMID- 9035377
TI  - Biological studies on 1,2-benzisothiazole derivatives VI Antimicrobial activity
      of 1,2-benzisothiazole and 1,2-benzisothiazolin-3-one derivatives and of some
      corresponding 1,2-benzisoxazoles.
AB  - Numerous 1,2-benzisothiazole and 1,2-benzisothiazolin-3-one derivatives,
      variously substituted in the different positions of the molecule, were tested for
      their in vitro antimicrobial activity. Some corresponding 1,2-benzisoxazoles and
      1,2-benzisoxazolin-3-ones were also considered. Several compounds possess a
      potent and broad antibacterial and antifungal activity, particularly against Gram
      positive microorganisms, yeasts and dermatophytes. 1,2-Benzisothiazolin-3-ones
      were found to be the most active substances. On the contrary, the benzisoxazoles
      and the benzisoxazolin-3-ones considered were devoid of activity. The results
      obtained are discussed on the basis of structure-activity relationships.

PMID- 9035378
TI  - 2-Aryl-6-methyl-3-phenylamino-6,7-dihydropyrano[4,3-c]pyrazol-4(2H)-ones with
      analgesic activity.
AB  - A series of 2-aryl-6-methyl-3-phenylamino-6,7-dihydropyrano[4,3-c]pyrazol-4(2H )
      ones were prepared and tested for antiinflammatory, analgesic, antipyretic,
      antiarrhythmic, antihypertensive and platelet antiaggregating activities. All of
      them showed an appreciable level of analgesic activity in mice.

PMID- 9035379
TI  - Synthesis and local anaesthetic activity of some 7-amino-2
      dialkylaminoalkylpyrrolo[3,4-c]pyridine derivatives.
AB  - A number of 7-amino-2-dialkylaminoalkylpyrrolo[3,4-c] pyridin-1,3(2H)-dione
      derivatives were synthesized and their local anaesthetic activity was evaluated
      in vivo by corneal anaesthesia in rabbits. Only compounds 3,9 and 14 showed any
      activity, albeit lower than that of the reference drug lidocaine.

PMID- 9035380
TI  - Synthesis and anticonvulsant activity of new 3-[(2-furyl)carbonyl]amino-4
      thiazolidinone and 2-[(2-furyl)carbonyl]hydrazono-4-thiazoline derivatives.
AB  - A series of new 2-aryl-3-[(2-furyl)carbonyl]amino-5-nonsubstituted/methyl-4-thi
      azolidinones (3) and 2-[(2-furyl)carbonyl]hydrazono-3-alkyl-4-aryl-4-thiazolines
      (5) was synthesized and evaluated for anticonvulsant activity against
      pentylenetetrazole induced seizures. Preliminary results indicated that potency
      was sensitive to substituents at the 2 and 5 positions of the 4-thiazolidinone
      and 3 and 4 positions of the 4-thiazoline rings. Among 3,2-(phenyl)/ (4
      fluorophenyl)-3-[(2-furyl)carbonyl]amino-5-methyl-4-thiazolidinone s (3e and 3f)
      and among 5, 2-[(2-furyl)carbonyl]hydrazono-3-allyl-4-(4-bromophenyl)-4-thiazol
      ine (5e), showed the highest protection (40%).

PMID- 9035381
TI  - Optimised method for determination of ticlopidine in serum by high performance
      liquid chromatography.
AB  - In this study we verified whether high performance liquid chromatography with UV
      detection (HPLC-UV) could be optimised and hence become a useful method for
      measuring ticlopidine concentrations in patient blood. The extraction step was
      improved by adding isoamylic alcohol in the extraction mixture, resulting in a
      better recovery. Moreover, the extraction efficiency was consistently ameliorated
      by evaporation to dryness of the organic extract; we could therefore utilise a
      lower (213 nm) wavelength, corresponding to the maximum of absorption, achieving
      a better sensitivity. With these technical improvements, the limit of
      quantitation is 0.02 microgram/ml, and the limit of detection is 0.01
      microgram/ml, hence comparable to levels obtained with gas-liquid chromatography
      with nitrogen detection (GC-NPD). In addition, HPLC method, if compared with GC
      NPD, is simpler and can be easily used for routine determinations of a lot of
      serum samples.

PMID- 9035382
TI  - Antihypertensive effect of dithiocarbamate derivatives.

PMID- 9035383
TI  - Synthesis and antimicrobial assays of 3-diazoindole-2-carboxamides.
AB  - Some 3-diazoindole-2-carboxamides have been synthesized and their antimicrobial
      activity have been tested. Antimicrobial activity was practically lacking.

PMID- 9035384
TI  - Developmental analysis of a female-specific 16S rRNA gene from mycetome
      associated endosymbionts of a mealybug, Planococcus lilacinus.
AB  - A clone showing female-specific expression was identified from an embryonic cDNA
      library of a mealybug, Planococcus lilacinus. In Southern blots this clone (P7)
      showed hybridization to genomic DNA of females, but not to that of males.
      However, P7 showed no hybridization to nuclei of either sex, raising the
      possibility that it was extrachromosomal in origin. In sectioned adult females P7
      hybridized to an abdominal organ called the mycetome. The mycetome is formed by
      mycetocytes, which are polyploid cells originating from the polar bodies and
      cleavage nuclei that harbour maternally transmitted, intracellular symbionts.
      Electron microscopy confirmed the presence of symbionts within the mycetocytes.
      Sequence analysis showed that P7 is a 16S rRNA gene, confirming its prokaryotic
      origin. P7 transcripts are localized to one pole in young embryos but are found
      in the pole as well as in the germ band during later stages of development. P7
      expression is detectable in young embryos of both sexes but the absence of P7 in
      third instar and adult males suggests that this gene, and hence the
      endosymbionts, are subject to sex-specific elimination.

PMID- 9035385
TI  - Receptors for the vasodilator maxadilan are expressed on selected neural crest
      and smooth muscle-derived cells.
AB  - Maxadilan is a potent vasodilator peptide isolated from salivary glands of the
      blood feeding sand fly Lutzomyia longipalpis. The peptide relaxes rabbit aortic
      rings in an endothelium independent manner while elevating levels of cAMP and has
      been found to bind to membrane homogenates from brain. These studies on tissues
      have now been expanded with an examination of binding and signaling of maxadilan
      to a number of established cell lines and primary cultures. The data reveal that
      maxadilan binds to and stimulates the accumulation of cAMP in the rat
      pheochromocytoma line PC12 and the human neuroblastoma line NBfl. Accumulation of
      cAMP occurred in a transformed mouse pancreatic smooth muscle line (MILE) and
      primary rabbit aorta smooth muscle cells. The peptide did not bind to or induce
      cAMP formation in the rat thoracic aorta line L6. Scatchard analysis of binding
      to the PC12 and NBfl lines indicates that maxadilan binds to a single class of
      high-affinity receptors. Similar pharmacologic actions and possible structural
      homologies between maxadilan and calcitonin gene-related peptide (CGRP) suggested
      the possibility that they shared receptors. However, competition studies and
      comparative second messenger analysis reveal that maxadilan does not interact
      with receptors for CGRP, amylin or adrenomedullin and suggest that this peptide
      may bind to a novel receptor whose endogenous ligand remains unknown.

PMID- 9035386
TI  - Allelic variation of the polyubiquitin gene in the tobacco hawkmoth, Manduca
      sexta, and its regulation by heat shock and programmed cell death.
AB  - The intersegmental muscles (ISMs) of the tobacco hawkmoth, Manduca sexta, undergo
      programmed cell death (PCD) following adult eclosion in response to a decline in
      the circulating titer of the hormone 20-hydroxyecdysone. The ability of the ISMs
      to die requires de novo gene expression and a number of cDNAs representing
      differentially expressed genes have been isolated from condemned cells. One of
      the genes that is dramatically up-regulated with ISM death is polyubiquitin,
      which has been shown in many organisms to function as a heat shock protein and as
      an essential mediator of proteolysis. Northern blot analysis of ISM RNA samples
      pooled from multiple individuals demonstrated the presence of several
      polyubiquitin transcripts. In this study, we sought to determine: 1) if these
      transcripts were the product of multiple genes or multiple alleles, and 2) if all
      polyubiquitin genes/alleles in the moth are regulated by both heat shock and the
      endocrine signals that regulate death. Data from Southern blot analysis suggested
      that the Manduca genome has a single polyubiquitin gene that is represented by
      multiple alleles. Transcript analysis supported the hypothesis that all
      polyubiquitin alleles are regulated by both heat shock and the hormonal cues that
      regulate muscle death. Polyubiquitin transcripts accumulated to much higher
      levels and had longer half-lives following hormonal induction relative to that
      seen in response to heat shock. These data suggest that there are multiple
      polyubiquitin alleles in the laboratory population of Manduca, all of which share
      common regulatory sequences that drive expression to meet the needs for
      proteolysis involved in both heat stress and death.

PMID- 9035387
TI  - Simultaneous determination of soluble sugars and organic acids as their
      trimethylsilyl derivatives in apricot fruits by gas-liquid chromatography.
AB  - The aim of this study was to determine a reliable procedure for the
      quantification of organic acids, alcohol soluble sugars and sugar alcohols in
      fruit flesh by means of a rapid GLC method, without resorting to methoximation of
      sugars and employing apricot as a model. The use of two internal standards, an
      accurate derivatization and a proper calibration of the GLC conditions allowed an
      accurate quantitative analysis of the compounds detected in the unknown samples.
      This simple procedure improves the speed of preparation of the trimethylsilyl
      derivatives and is highly reproducible. Variability was found between years for
      each of the five cultivars studied and for each compound in terms of absolute
      values, whereas the percentage incidence of the single sugars as a total was more
      stable over the two years of observation.

PMID- 9035388
TI  - Validated high-performance liquid chromatographic method for quantitation of
      neohesperidine dihydrochalcone in foodstuffs.
AB  - An analytical method to detect and quantitate neohesperidine dihydrochalcone in
      foodstuffs has been developed and validated in soft-drink applications. The
      method was shown to be sufficiently precise, accurate, selective and rugged in
      quantitating neohesperidine DC both at flavouring (1-5 mg/kg) and sweetening (5
      50 mg/kg) levels. Applications of the method to determine neohesperidine DC in
      foodstuffs other than soft-drinks is also described.

PMID- 9035389
TI  - Regulation of the Arabidopsis thaliana aquaporin gene AthH2 (PIP1b).
AB  - Arabidopsis thaliana was transformed with constructs composed of the aquaporin
      AthH2 promoter and the coding sequence of beta-glucuronidase (GUS) as reporter
      gene. The transgenic plants obtained were treated with different light qualities
      or phytohormones and the activity of the AthH2 promoter was determined in situ
      using a specific GUS assay. With blue light (400-550 nm) and white light,
      significant activation of the promoter was observed. The same was true for the
      application of gibberellic acid (GA) and abscisic acid (ABA). In contrast, red
      light and indole-3-acetic acid (IAA) had only minor effects on the promoter
      activity. The significance of sequence elements with relation to GA or ABA was
      confirmed by deletion analyses of the AthH2 promoter. Likewise, a promoter
      segment with importance for hydathoid specific expression was identified.

PMID- 9035390
TI  - Temporal integration of loudness, loudness discrimination, and the form of the
      loudness function.
AB  - Temporal integration for loudness of 5-kHz tones was measured as a function of
      level between 2 and 60 dB SL. Absolute thresholds and levels required to produce
      equal loudness were measured for 2-, 10-, 50-, and 250-ms tones using adaptive,
      two-interval, two-alternative forced-choice procedures. The procedure for
      loudness balances was new and employed ten interleaved tracks to obtain
      concurrent measurements for ten tone pairs. Each track converged at the level
      required to make the variable stimulus just louder than the fixed stimulus. Thus,
      the data yield estimates of the just-noticeable difference (jnd) for loudness
      level and temporal integration for loudness. Results for four listeners show that
      the amount of temporal integration, defined as the level difference between
      equally loud short and long tones, varies markedly with level and is largest at
      moderate levels. The effect of level increases as the duration of the short
      stimulus decreases and is largest for comparisons between the 2- and 250-ms
      tones. The loudness-level jnds are also largest at moderate levels and, contrary
      to traditional jnds for the level of two equal-duration tones, they do not appear
      to depend on duration. The latter finding indicates that loudness discrimination
      between stimuli that differ along multiple dimensions is not the same as level
      discrimination between stimuli that differ only in level. An equal-loudness-ratio
      model, which assumes that the ratio of loudnesses for a long and short tone at
      equal SPL is the same at all SPLs, can explain the level dependence of temporal
      integration and the loudness jnds. It indicates that the loudness function
      [log(loudness) versus SPL] is flatter at moderate levels than at low and high
      levels in agreement with earlier findings for 1-kHz tones [M. Florentine et al.,
      J. Acoust. Soc. Am. 99, 1633-1644 (1996)].

PMID- 9035391
TI  - A re-examination of risk estimates from the NIOSH Occupational Noise and Hearing
      Survey (ONHS)
AB  - This paper describes a new analysis of data from the 1968-72 National Institute
      for Occupational Safety & Health (NIOSH) Occupational Noise and Hearing Survey
      (ONHS). The population consisted of 1172 (792 noise-exposed and 380 "controls")
      predominately white male workers from a cross section of industries within the
      United States. The analysis focused on how risk estimates vary according to
      various model assumptions, including shape of the dose-response curve and the
      amount of noise exposure among low-noise exposed workers (or controls). Logistic
      regression models were used to describe the risk of hearing handicap in relation
      to age, occupational noise exposure, and duration exposed. Excess risk estimates
      were generated for several definitions of hearing handicap. Hearing handicap is
      usually denoted as an average hearing threshold level (HTL) of greater than 25 dB
      for both ears at selected frequencies. The frequencies included in the biaural
      averages were (1) the articulation-weighted average over 1-4 kHz, (2) the
      unweighted average over 0.5, 1, and 2 kHz, and (3) the unweighted average over 1,
      2, and 3 kHz. The results show that excess risk estimates for time-weighted
      average sound levels below 85 dB were sensitive to statistical model form and
      assumptions regarding the sound level to which the "control" group was exposed.
      The choice of frequencies used in the hearing handicap definition affected the
      magnitude of excess risk estimates, which depended on age and duration of
      exposure. Although data were limited below 85 dB, an age-stratified analysis
      provided evidence of excess risks at levels ranging from 80 to 84 dB, 85-89 dB,
      and 90-102 dB. Due to uncertainty in quantifying risks below 85 dB, new data
      collection efforts should focus on better characterization of dose-response and
      longitudinal hearing surveys that include workers exposed to 8-hour time-weighted
      noise levels below 85 dB. Results are compared to excess risk estimates generated
      using methods given by ANSI S3.44-1996.

PMID- 9035392
TI  - Auditory-nerve fiber responses to clicks in guinea pigs with a damaged cochlea.
AB  - This paper describes auditory-nerve single-fiber responses to clicks in noise
      damaged cochleas. Poststimulus time histograms (PSTHs) were recorded for various
      click intensities and for the two click polarities. The PSTHs found in fibers
      with elevated thresholds are discussed in relation to the frequency threshold
      curves (FTCs) measured in these fibers. Five types of abnormal FTCs are
      distinguished. Type I is elevated as a whole, type II has an elevated (and often
      broadened) tip and a tail at normal level, type III has low thresholds in the
      tail (often hypersensitive), type IV represents a flat tuning, and type V has no
      tip but shows a clear appearance of the tail (often hypersensitive). The click
      PSTHs of abnormal fibers were compared to normal PSTHs at equal sound-pressure
      levels, and various abnormal trends were found corresponding to the type of FTC.
      PSTHs for type I have longer dominant-peak latencies and smaller amplitudes;
      PSTHs for type II were normal well above the fiber's threshold; PSTHs for type
      III revealed remarkable patterns with multiple peaks, part of them with a latency
      strongly varying with polarity; PSTHs for type IV showed narrow peaks and steep
      amplitude/intensity curves; PSTHs for type V showed a multiple peaked pattern and
      large amplitudes and steep amplitude/intensity curves to rarefaction polarity.
      The various features in the click responses were in most cases consistent with
      the type of FTC. The results can be used to explain deviations in whole-nerve
      recordings in abnormal cochleas.

PMID- 9035393
TI  - Masking of a brief probe by sinusoidal frequency modulation.
AB  - Contrary to level detection models, the thresholds for a brief-duration probe
      masked by a sinusoidal frequency modulation (FM) masker increases as the
      modulation index (beta) of FM increases [Zwicker, Acustica 31, 243-256 (1974)].
      In this paper the reason for this phenomenon is investigated. In experiment 1, a
      10-ms, 1-kHz probe was detected in the presence of an FM masker centered at 1 kHz
      and sinusoidally modulated at 16 Hz. Thresholds increased by over 15 dB with
      increasing beta, consistent with Zwicker's findings. In experiment 2, the
      instantaneous frequency changes of the masker used in experiment 1 were clipped
      and the resulting thresholds indicated that detection was determined primarily by
      the masker's total frequency excursion rather than by its instantaneous sweep
      rate. In experiment 3, the FM maskers from the first two experiments were passed
      through a roex filter centered at 1 kHz and the resulting envelope was used to
      amplitude modulate a 1-kHz tone, producing approximately the same effective
      envelope at 1 kHz as the FM maskers. Threshold functions for the amplitude
      modulated (AM) maskers were similar to those for their corresponding FM maskers.
      Thresholds increased by over 15 dB while the total energy of the AM masker
      decreased by over 10 dB, again contrary to standard level-detection models. The
      results from these experiments can be explained, at least qualitatively, by a
      model based on envelope shape discrimination: similarities between the envelopes
      of the masker alone and masker-plus-probe at the output of an auditory filter
      centered on the frequency of the probe are primarily responsible for the observed
      masking, particularly at large beta's.

PMID- 9035394
TI  - A new way to account for binaural detection as a function of interaural noise
      correlation.
AB  - The purpose of this communication is to describe a new method for predicting
      masking level differences (MLDs) as a function of the interaural correlation of
      the masking noise. The general idea is to decompose a binaural noise masker
      having an arbitrary value of interaural correlation into two parts: an No
      constituent and an N pi constituent. It is shown that the amount of masking
      produced by a noise having an arbitrary interaural correlation is equal to the
      addition of the masking effects produced by the No and N pi constituents that
      compose the masker. The new approach was used to generate predictions of MLDs for
      N rho S pi and N rho So conditions. Those predictions accounted for 98% of the
      variance in the classical data of Robinson and Jeffress [J. Acoust. Soc. Am. 35,
      1947-1952 (1963)]. Finally, it is shown that the "additivity of masking" method
      is mathematically equivalent to assuming that binaural detection consists of a
      stage of errorless binaural processing preceded by a corrupted representation of
      the stimulus.

PMID- 9035395
TI  - On the Duifhuis pitch effect.
AB  - An effect discovered by Duifhuis [J. Acoust. Soc. Am. 48, 888-893 (1970)],
      wherein an omitted high harmonic of a periodic complex tone is found to have an
      audible pitch, is extended to a variety of new broadband signal conditions. The
      effect is found to exist for flat spectra and spectra decreasing at 6 dB/octave,
      independent of phases as long as they are constant. The effect exists for
      alternating phases and Schroeder phases. It can generate a missing-fundamental
      pitch. Pitch and loudness matching experiments support the status of the omitted
      harmonic as an objective tone in the signal. Further experiments using narrower
      bands challenge the traditional explanation for the effect, which attributes it
      to short-term frequency analysis by peripheral auditory filters. Instead, the
      experiments suggest that different peripheral channels must be combined,
      maintaining some phase information, to generate the effect.

PMID- 9035396
TI  - The relation between gap detection, loudness, and loudness growth in noise-masked
      normal-hearing listeners.
AB  - Gap detection was measured for 50 and 1000-Hz-wide noise markers arithmetically
      centered on 1000 Hz. The markers were presented in a lowpass background noise
      having a high-frequency cutoff of 2000 Hz. The pressure spectrum level of the
      background noise was either 0 or 40 dB/Hz. Gap detection was determined at
      sensation levels (SLs) of 10, 15, 20, and 30 dB in the 0-dB/Hz background, and at
      SLs of 10, 15, and 20 dB in the 40-dB/Hz background. Because loudness increased
      more steeply in the higher level noise background, the markers in the 40-dB/Hz
      background were at higher loudness (and at a steeper portion of the loudness
      growth function) than markers in the 0-dB/Hz background, for markers matched in
      terms of SL. The main goal of the experiment was to determine whether gap
      detection would be relatively poor at steep portions of the loudness growth
      function due to the gap being confused with ongoing random dips. Such confusion
      might be particularly great when the noise bandwidth was narrow (and therefore
      characterized by prominent fluctuation) and the growth of loudness was steep. Gap
      detection was poorer for the 50-Hz-wide marker than for the 1000-Hz-wide marker.
      For a given marker bandwidth at a given SL, gap detection was similar whether the
      marker was presented in the 0-dB/Hz noise or the 40-dB/Hz noise. Supplementary
      conditions indicated that (1) gap detection results for 50-Hz-wide markers
      presented at equal SL's were also similar between a 0-dB/Hz noise background and
      a 55-dB/Hz noise background, and that (2) gap detection for 50- and 1000-Hz-wide
      markers was poorer in a 40-dB/Hz background than in a 0-dB/Hz background when
      markers were matched for loudness. The results generally indicated similar gap
      detection thresholds for markers presented at similar SLs across a relatively
      wide range of background noise levels. Gap detection was related more closely to
      the marker-to-noise ratio than to the loudness relation between markers or the
      steepness of loudness growth.

PMID- 9035397
TI  - Monaural sound localization revisited.
AB  - Research reported during the past few decades has revealed the importance for
      human sound localization of the so-called "monaural spectral cues." These cues
      are the result of the direction-dependent filtering of incoming sound waves
      accomplished by the pinnae. One point of view about how these cues are extracted
      places great emphasis on the spectrum of the received sound at each ear
      individually. This leads to the suggestion that an effective way of studying the
      influence of these cues is to measure the ability of listeners to localize sounds
      when one of their ears is plugged. Numerous studies have appeared using this
      monaural localization paradigm. Three experiments are described here which are
      intended to clarify the results of the previous monaural localization studies and
      provide new data on how monaural spectral cues might be processed. Virtual sound
      sources are used in the experiments in order to manipulate and control the
      stimuli independently at the two ears. Two of the experiments deal with the
      consequences of the incomplete monauralization that may have contaminated
      previous work. The results suggest that even very low sound levels in the
      occluded ear provide access to interaural localization cues. The presence of
      these cues complicates the interpretation of the results of nominally monaural
      localization studies. The third experiment concerns the role of prior knowledge
      of the source spectrum, which is required if monaural cues are to be useful. The
      results of this last experiment demonstrate that extraction of monaural spectral
      cues can be severely disrupted by trial-to-trial fluctuations in the source
      spectrum. The general conclusion of the experiments is that, while monaural
      spectral cues are important, the monaural localization paradigm may not be the
      most appropriate way to study their role.

PMID- 9035398
TI  - Toward articulatory-acoustic models for liquid approximants based on MRI and EPG
      data. Part I. The laterals.
AB  - Magnetic resonance images of the vocal tract during the sustained phonation of
      /l/ (both dark and light allophones) by four native American English talkers are
      employed for measuring lengths, area functions, and cavity volumes and for the
      analysis of 3-D vocal tract and tongue shapes. Electropalatography contact
      profiles are used for studying inter- and intra-talker variabilities and as a
      source of converging evidence for the magnetic resonance imaging study. The
      general 3-D tongue body shapes for both allophones of /l/ are characterized by a
      linguo-alveolar contact together with inward lateral compression and convex cross
      sections of the posterior tongue body region. The lateral compression along the
      midsagittal plane enables the creation of flow channels along the sides of the
      tongue. The bilateral flow channels exhibit somewhat different areas, a
      characteristic which is talker-dependent. Dark /l/s show smaller pharyngeal areas
      than the light varieties due to tongue-root retraction and/or posterior tongue
      body raising. The acoustic implications of the observed geometries are discussed.

PMID- 9035399
TI  - Toward articulatory-acoustic models for liquid approximants based on MRI and EPG
      data. Part II. The rhotics.
AB  - Magnetic resonance images of the vocal tract during sustained production of
      [symbol: see text] by four native American English talkers are employed for
      measuring vocal-tract dimensions and for morphological analysis of the 3D vocal
      tract and tongue shapes. Electropalatography contact profiles are used for
      studying inter- and intra-talker variabilities. The vocal tract during the
      production of [symbol: see text] appears to be characterized by three cavities
      due to the presence of two supraglottal constrictions: the primary one in the
      oral cavity, and a secondary one in the pharyngeal cavity. All subjects show a
      large volume anterior to the oral constriction, which results from an inward
      drawn tongue body, an anterior tongue body that is characterized by convex cross
      sections, and a concave posterior tongue body shape. Inter-subject variabilities
      are observed in the oral-constriction location and the way the constriction is
      formed. No systematic differences are found between the 3-D vocal tract and
      tongue shapes of word-initial and syllabic [symbol: see text]s. Tongue-shaping
      mechanisms for these sounds and their acoustic implications are discussed.

PMID- 9035400
TI  - Perceptual magnet effect in the light of behavioral and psychophysiological data.
AB  - Finnish speaking adults categorized synthetic vowels, varying in the frequency of
      the second formant (F2), as either /y/ or /i/. Two subject groups emerged: "good"
      and "poor" categorizers. In a /i/ rating experiment, only the good categorizers
      could consistently label their best /i/ (the prototype, P), being low in the F2
      continuum. Poor categorizers rated /i/'s with high F2 values as Ps. In a
      same/different (AX) discrimination experiment, using the individual Ps and
      nonprototypes (NPs), it was more difficult for good categorizers to detect small
      F2 deviations from the P than from an NP (the "perceptual magnet effect"). For
      poor categorizers, the opposite effect was found. The same stimuli were used to
      record the mismatch negativity (MMN), an ERP component reflecting preattentive
      detection of deviations from a standard sound. For the good categorizers the MMNs
      were lower for Ps than for NPs; for the poor categorizers the MMNs for Ps and NPs
      did not differ significantly. The results show that individual listeners behaved
      differently in categorization and goodness rating but in the same way in
      attentive (AX) discrimination, being the poorest at about the same F2 location.
      The perceptual magnet effect was indicated in the good categorizers both by
      behavioral and psychophysiological (MMN) discrimination data.

PMID- 9035401
TI  - Error analysis in acoustic elastography. I. Displacement estimation.
AB  - Correlation between acoustic echo signals obtained before and after application
      of an external compressional force provides information about the internal
      deformation of an elastic medium. In this paper, the variance for displacement
      estimated from an echo data segment and the covariance between two windowed
      segments that may overlap are derived. The signal and noise spectra are Gaussian
      and independent. The dependence of the displacement variance on input signal-to
      noise ratio (SNRi), time-bandwidth product W, fractional bandwidth Y-1, and the
      rate of displacement variation with depth a is investigated. The relationship
      between a and the other experimental parameters is crucial for understanding how
      signal decorrelation affects displacement error. The expression for displacement
      variance reduces to the Cramer-Rao lower bound result when a = 0 and W > > 1 for
      both bandpass and base-band signals. When a not equal to 0 displacement variance
      increases, and there is an optimal window length at W = square root of 20/a
      square root of 1 + Y2 for which the displacement variance is minimum. Narrow-band
      signals produce larger errors than broadband signals for long observation windows
      when a not equal to 0 and just the opposite when a = 0. Errors are greatest for
      displacements estimated from the envelope of narrow-band signals. Finally, a
      general expression for the minimum displacement variance for arbitrary signal and
      noise spectra is derived as a function of the experimental parameters. These
      results form a framework for analyzing strain estimates in elastography, the
      subject of a companion paper.

PMID- 9035402
TI  - Error analysis in acoustic elastography. II. Strain estimation and SNR analysis.
AB  - Accurate displacement estimates are required to obtain high-quality strain
      estimates in elastography. In this paper the strain variance is derived from the
      statistical properties of the displacement field to define a point signal-to
      noise ratio for elastography (SNR0). Displacements caused by compressional forces
      applied along the axis of the transducer beam are modeled by scaling and shifting
      the axial reflectivity profile of the tissue. The strain variance is given as a
      function of essential experimental parameters, such as the amount of tissue
      compression, echo waveform window length, and the amount of window overlap. SNR0
      is defined in terms of applied compression and strain variance and normalized by
      the input signal-to-noise ratio (SNRi) for echo signals, to formulate the
      performance metric SNR0/SNRi. This quantity characterizes the noise properties,
      dynamic range, and sensitivity of strain images based on the spatial resolution
      requirements. The results indicate that low noise, high sensitivity, and limited
      dynamic range strain images are obtained for high-frequency bandpass signals when
      the applied strain is small. For large strains, however, one strategy for low
      noise strain imaging employs base-band signals to obtain images with large
      dynamic range but limited peak sensitivity and noise figure. A better strategy
      includes companding, which eliminates the average strain in the echo signal
      before cross-correlation to reduce the dynamic range requirement and increase
      peak sensitivity for strain estimates.

PMID- 9035403
TI  - Harmonic amplitude distribution in a wideband ultrasonic wavefront after
      propagation through human abdominal wall and breast specimens.
AB  - The amplitude characteristics of ultrasonic wavefront distortion produced by
      transmission through the abdominal wall and breast is described. Ultrasonic
      pulses were recorded in a two-dimensional aperture after transmission through
      specimens of abdominal wall or breast. After the pulse arrival times were
      corrected for geometric path differences, the pulses were temporally Fourier
      transformed and two-dimensional maps of harmonic amplitudes in the measurement
      aperture were computed. The results indicate that, as the temporal frequency
      increases, the fluctuation in harmonic amplitudes increases but the spatial scale
      of the fluctuation decreases. The normalized second-order and third-order moments
      of the amplitude distribution also increase with temporal frequency. The wide
      range variation of these distribution characteristics could not be covered by the
      Rayleigh, Rician, or K-distribution because of their limited flexibility.
      However, the Weibull distribution and especially the generalized K-distribution
      provide better fits to the data. In the fit of the generalized K-distribution, a
      decrease of its parameter alpha with increasing temporal frequency was observed,
      as predicted by analysis based on a phase screen model.

PMID- 9035404
TI  - The frequency response of the ER-2 speaker at the eardrum.

PMID- 9035405
TI  - Efficient production of secreted proteins by Aspergillus: progress, limitations
      and prospects.
AB  - Filamentous fungi are widely used for the production of homologous and
      heterologous proteins but, compared to homologous proteins, the levels of
      production of heterologous proteins are usually low. During the last 5 years, the
      levels of production of heterologous proteins have been drastically improved by
      fusing the corresponding gene to the 3' end of a homologous gene, encoding a well
      secreted protein such as glucoamylase. Nevertheless, little research has been
      carried out to determine the limitations that hamper heterologous protein
      production. Recently we have carried out a detailed analysis of the levels of
      production of several proteins and glucoamylase fusion proteins in defined
      recombinant Aspergillus awamori strains. In this review we will focus on the use
      of filamentous fungi for the production of heterologous, especially non-fungal
      proteins. In particular, the effect of gene-fusion strategies will be reviewed.
      Furthermore, the remaining limitations in heterologous protein production and
      suggestions for improvement strategies for overproduction of these protein will
      be discussed.

PMID- 9035406
TI  - Electrochemical disinfection of drinking water using an activated-carbon-fiber
      reactor capable of monitoring its microbial fouling.
AB  - An electrochemical reactor employing activated carbon fibers (ACF) was
      constructed for the disinfection of bacteria in drinking water. The application
      of an alternating potential of 1.0 V and -0.8 V versus a saturated calomel
      electrode, for disinfecting and desorbing bacteria, enabled reactor operation for
      840 h. Drinking water was passed through the reactor in stop/flow mode: 300
      ml/min flow for 12 h and no flow for 12 h, alternately. The bacterial cell
      density in treated water was always been less than 20 cells/ml. It was also found
      that the formation of biofilm on the ACF reactor caused an increase in current,
      enabling the self-detection of microbial fouling.

PMID- 9035407
TI  - Synthetic spider dragline silk proteins and their production in Escherichia coli.
AB  - Synthetic genes were designed to encode analogs of the two proteins of Nephila
      clavipes dragline silk, spidroins 1 and 2. The genes were constructed of tandem
      repeats of relatively long (more than 300 bp) DNA sequences assembled from
      synthetic oligonucleotides, and encoded proteins of high molecular mass (65-163
      kDa). Both analogs were produced efficiently in Escherichia coli. The yield and
      homogeneity of the products of longer genes were limited by premature termination
      of synthesis, probably as a result of processivity errors in protein synthesis.
      Average termination rates were determined to be 1 in 1100 codons to 1 in 300
      codons, depending on the length and synonymous codon choices of the gene. Both
      analog proteins could be induced to form stable aqueous solutions without
      denaturants. Circular dichroism spectra of the purified proteins in dilute
      solution resembled spectra of redissolved natural dragline silk in reflecting a
      largely disordered structure in water and more ordered structures in mixed
      solvents with methanol and trifluoroethanol.

PMID- 9035408
TI  - Production of synthetic spider dragline silk protein in Pichia pastoris.
AB  - The methylotrophic yeast Pichia pastoris was tested as a host for the production
      of long, repetitive protein polymers. Synthetic genes for a designed analog of a
      spider dragline silk protein were readily expressed at high levels under control
      of the methanol-inducible AOX1 promoter. Transformants containing multiple gene
      copies produced elevated levels of silk protein, but of a variety of altered
      sizes as a result of gene rearrangements at the time of transformation. Genes up
      to 3000 codons in length or longer could be expressed with no evidence of the
      prevalent truncated synthesis observed for similar genes in Escherichia coli,
      though genes longer than 1600 codons were expressed less efficiently than shorter
      genes. Silk-producing P. pastoris strains were stable without selection for at
      least 100 doublings.

PMID- 9035409
TI  - Improvement of culture conditions to overproduce beta-galactosidase from
      Escherichia coli in Bacillus subtilis.
AB  - The effect of some culture variables in the production of beta-galactosidase from
      Escherichia coli in Bacillus subtilis was evaluated. The lacZ gene was expressed
      in B. subtilis using the regulatory region of the subtilisin gene aprE. The host
      contained also the hpr2 and degU32 mutations, which are known to overexpress the
      aprE gene. We found that, when this overproducing B. subtilis strain was grown in
      mineral medium supplemented with glucose (MMG), beta-galactosidase production was
      partially growth-associated, as 40%-60% of the maximum enzyme activity was
      produced before the onset of the stationary phase. In contrast, when a complex
      medium was used, beta-galactosidase was produced only at low levels during
      vegetative growth, whereas it accumulated to high levels during early stationary
      phase. Compared with the results obtained in complex media, a 20% increase in
      specific beta-galactosidase activity in MMG supplemented with 11.6 g/l glucose
      was obtained. On the 1-1 fermenter scale, a three-fold increase in volumetric
      beta-galactosidase activity was obtained when the glucose concentration was
      varied from 11 g/l to 26 g/l. In addition, glucose feeding during the stationary
      phase resulted in a twofold increase in volumetric enzyme activity as cellular
      lysis was prevented. Finally, we showed that oxygen uptake and carbon dioxide
      evolution rates can be used for on-line determination of the onset of stationary
      phase, glucose depletion and biomass concentration.

PMID- 9035410
TI  - Cold adaptation of a mesophilic serine protease, subtilisin, by in vitro random
      mutagenesis.
AB  - Artificial cold adaptation of a mesophilic protease, subtilisin BPN' was
      attempted by means of random mutagenesis of its entire gene coupled with
      screening of cleared-zone-forming colonies on skim-milk plates at a low
      temperature. Out of sixty clones screened at 10 degrees C, one mutant enzyme
      (termed M-15) was found to acquire higher proteolytic activities, specifically
      dependent on low temperatures ranging from 10 degrees C to 1 degree C, in
      comparison with those of the wild-type. DNA sequencing analysis revealed that, by
      this mutation, the 84th amino acid residue, valine, was substituted by
      isoleucine, which is located 1.5 nm from the center of the catalytic triad in the
      tertiary structure of subtilisin. By kinetic analysis of the purified enzyme
      samples, the higher proteolytic activities of M-15 at low temperatures were found
      to be due to the decrease in the Km value. There was no difference in
      thermostability between the wild-type and mutant enzymes, when tested by heat
      treatment. Circular dichroism spectra also showed no difference between them at
      10 degrees C, indicating that the mutation of V841 had no effect on the secondary
      structure of subtilisin.

PMID- 9035412
TI  - Use of immobilized bacteria to treat industrial wastewater containing a
      chlorinated pyridinol.
AB  - Pseudomonas sp. strain M285 immobilized on diatomaceous earth beads was used to
      remove 3,5,6-trichloro-2-pyridinol (TCP) from industrial wastewater. Batch
      studies showed that immobilized Pseudomonas sp. strain M285 mineralized [2,6
      14C]TCP rapidly; about 75% of the initial radioactivity was recovered as 14CO2.
      Transformation of TCP was inhibited by high concentrations of salt, and addition
      of osmoprotectants (proline and betaine at 1 mM) did not reduce the adverse
      effect of salt. TCP-containing wastewater (60-140 mg/l) was passed through
      columns containing immobilized Pseudomonas sp. strain M285 at increasing flow
      rates and increasing TCP concentrations; TCP removal of 80%-100% was achieved.
      Addition of nutrients, such as glucose and yeast extract, retarded TCP
      degradation. Growing cell cultures were found to be better inocula for
      immobilization than resting cells.

PMID- 9035411
TI  - Biodegradation of methyl t-butyl ether by pure bacterial cultures.
AB  - Three pure bacterial cultures degrading methyl t-butyl ether (MTBE) were isolated
      from activated sludge and fruit of the Gingko tree. They have been classified as
      belonging to the genuses Methylobacterium, Rhodococcus, and Arthrobacter. These
      cultures degraded 60 ppm MTBE in 1-2 weeks of incubation at 23-25 degrees C. The
      growth of the isolates on MTBE as sole carbon source is very slow compared with
      growth on nutrient-rich medium. Uniformly-labeled [14C]MTBE was used to determine
      14CO2 evolution. Within 7 days of incubation, about 8% of the initial
      radioactivity was evolved as 14CO2. These strains also grow on t-butanol, butyl
      formate, isopropanol, acetone and pyruvate as carbon sources. The presence of
      these compounds in combination with MTBE decreased the degradation of MTBE. The
      cultures pregrown on pyruvate resulted in a reduction in 14CO2 evolution from
      [14C]MTBE. The availability of pure cultures will allow the determination of the
      pathway intermediates and the rate-limiting steps in the degradation of MTBE.

PMID- 9035414
TI  - The American Federation for Medical Research, Southern section annual meetings.
      New Orleans, Louisiana, February 1997. Abstracts.

PMID- 9035413
TI  - [Progress report for the period 1 January 1995-31 December 1995].

PMID- 9035415
TI  - The American Federation for Medical Research, Western section annual meetings.
      Carmel, California, February 1997. Abstracts.

PMID- 9035416
TI  - Eastern Society for Pediatric Research annual meeting. Atlantic City, New Jersey,
      March 1997. Abstracts.

PMID- 9035417
TI  - XIIth International Biophysics Congress. Amsterdam, The Netherlands, 11-16 August
      1996. Abstracts.

PMID- 9035418
TI  - [To cure the health care system, everybody's business].

PMID- 9035419
TI  - [Surgical treatment of synchronous hepatic metastases of colorectal cancers.
      Simultaneous or delayed resection?].
AB  - The surgical strategy for resectable synchronous hepatic metastases of colorectal
      cancer remains controversial. The retrospective analysis of our series of
      resectable synchronous hepatic metastases focused on the percentage of
      simultaneous resections, the circumstances, the indications and the results of
      the one-step procedure compared to the two-step strategy. From January 1, 1982 to
      December 31, 1995, 129 patients were operated on for resection of hepatic
      metastases of colorectal cancer. Forty one patients (32%) presented with
      synchronous hepatic metastases, 20 of whom (49%) underwent simultaneous resection
      of the primary tumor and the hepatic metastases (simultaneous resection group:
      SR). For the other 21 patients (51%), the hepatic resection was delayed for a
      mean interval of 5.2 +/- 4.2 months (delayed resection group: DR). The mean age
      of the 2 groups was not significantly different (54 years versus 58 years). When
      the primary tumor was located on the ascending colon, the hepatic excision was
      performed simultaneously in 9 out of ten cases. The need for blood transfusion
      and the volume required were not significantly different between the two groups.
      The length of each surgical operation was comparable between the two groups (331
      +/- 76 minutes SR vs 330 +/- 88 minutes DR). Postoperative complications were
      observed in 20% of patients in the SR group and 10% of patients in the DR group
      (no significative difference). There was no postoperative mortality in either
      group. Survival was 83%, 44% and 37% at 1, 2 and 3 years respectively in the SR
      group and 79%, 59% and 49% in the DR group, with no significant difference
      between the groups. These results show that simultaneous resection of the primary
      tumor and the hepatic metastases did not increase either morbidity or mortality
      in our study, and that it should be proposed especially to patients presenting
      with a primary tumor of the ascending colon with metastases resectable by means
      of a minor hepatectomy.

PMID- 9035420
TI  - [Preservation of the pylorus in duodenopancreatectomy].
AB  - The authors present an overview of the technique of pancreatoduodenectomy with
      pylorus preservation. The main technical variants since the original description
      by Traverso and Longmire in 1978 are described. Advantages and drawbacks of the
      technique from a carcinologic and functional point of view are presented and
      discussed. Pancreatoduodenectomy with pylorus preservation appears to be the
      procedure of choice in most cases. However, it should be avoided in a few
      patients with invasion of the proximal duodenum by a periampullary carcinoma for
      whom a curative resection requires the addition of a gastrectomy.

PMID- 9035421
TI  - [Attempt at preventing hyperacute xenogenic rejection by isotopic suppression of
      IgM in the recipient].
AB  - Hyperacute xenogeneic rejection is partly initiated by the binding of performed
      natural antibodies on the recipient's vascular endothelium. In this study,
      isotypic suppression of IgM in the recipient was conducted in the guinea pig-to
      rat combination. Anti-IgM HIS 40 and 56 monoclonal antibodies were injected
      intraperitoneally in rats (n = 3) (Group 1). Control animals were rats (n = 13)
      treated by PBS (Group 2). Guinea pig hearts were implanted heterotopically in all
      rats. Depletion of circulating IgM in the recipient was assessed by ELISA. The
      circulating and splenic B-lymphocyte population was scanned by FACS analysis.
      Isotypic suppression was very effective for the depletion of circulating IgM in
      Group 1 rats (alpha < 0.01) as assessed by ELISA. Similarly, the rate of
      circulating and splenic B-lymphocytes was significantly decreased in treated
      animals (alpha < 0.01). However, the graft survival in Group 1 (14 +/- 6.9 min)
      was not different from that observed in Group 2 (15.4 +/- 5 min). Isotypic
      suppression of IgM in the recipient did not delay hyperacute xenogenic rejection
      in the guinea pig-to-rat combination. The prevention of hyperacute rejection must
      therefore be based on the various mechanisms of this phenomenon.

PMID- 9035422
TI  - [Value of percutaneous hepatic biopsy in the diagnosis of presumed benign tumors
      of the liver].
AB  - The purpose of this study was to assess the accuracy of guided hepatic biopsy
      (GHB) and imaging techniques for presumed benign liver tumours and to determine
      their impact on surgical treatment. The study was carried out retrospectively in
      a surgical series of 15 consecutive patients with presumed benign liver tumours.
      The final diagnosis was 8 cases of focal nodular hyperplasia (FNH), 6 hepatic
      adenomas (HA) and one association FNH-HA. No morbidity was related to guided
      hepatic biopsy. All FNH detected on radiologic imaging or pathological
      examination of the biopsy specimen were true positive diagnoses. This study
      demonstrates that combined results of imaging techniques and percutaneous GHB
      could correctly diagnose three quarters of FNH before surgery. GHB is also useful
      when MRI imaging is indeterminate allowing a conservative approach for
      undiagnosed FNH.

PMID- 9035423
TI  - [Genetics of Hirschsprung disease].
AB  - Hirschsprung's disease (HD) is one of the commonest gastrointestinal
      malformations, as it affects one child out of 5,000 births. It classically
      induces severe neonatal intestinal obstruction requiring surgical treatment which
      currently ensures a favourable prognosis for most of the affected children.
      Although the great majority of cases are sporadic, the existence of familial
      forms (10% of cases) has allowed localization and then identification of an
      autosomal dominant gene on chromosome 10, the RET proto-oncogene, responsible for
      50% of familial forms and 15% of sporadic cases. A second gene has been recently
      localized on chromosome 13, the endothelium beta receptor (EDNRB) gene. Two
      homozygous mutations of the EDNRB gene have been identified in two consanguineous
      families, in which HD is associated with Waardenburg's syndrome (WS). Other
      heterozygous mutations have been identified in patients presenting with isolated
      HD and an 5% of cases of HD can be considered to present mutations of this gene.
      Finally, the authors have recently identified a mutation of the endothelium gene
      3 (EDN3), one of the EDNRB ligands in a patient presenting with a combination of
      HD and WS. This mutation, present at the homozygous state in this patient, is
      predictive of complete absence of EDN3 protein: this is therefore the third known
      gene responsible for HD.

PMID- 9035426
TI  - [Diagnostic management of thyroid nodule].

PMID- 9035424
TI  - [Laparoscopy-assisted colonic surgery. Initial experience. Apropos of 49 cases].
AB  - From November 1993 to December 1995, 49 colonic operations were performed by a
      videolaparoscopic assisted approach. Indications were malignant conditions in 10
      cases, benign diseases in 39 cases (diverticular disease: 28, benign tumour: 9,
      reversal of Hartmann's procedure: 1, volvulus: 1). Conversion to a classical
      procedure was necessary in 6 patients. There was no mortality and 6 postoperative
      complications (3 reoperations). Colonic surgery this type of (laparoscopic
      assisted operations) is technically feasible. It reduces the rate of post
      operative wound complications and decreases the post-operative stay. It can be
      recommended for the surgical treatment of benign colonic diseases.

PMID- 9035427
TI  - [Post-partum malignant amebic colitis. Apropos of a case].
AB  - A 26-year old female developed acute fulminant amoebic colitis during the post
      partum period, successfully managed by subtotal colonic resection without
      anastomosis. Fulminant transmural amoebic colitis is a rare life-threatening
      complication of invasive bowel amebiasis. Pregnancy, delivery, diabetes mellitus
      and immunodeficiency are the main risk factors. At pathologic examination, bowel
      wall necrosis can be seen with amoebae present in the lumen of capillary vessels.
      The diagnosis of amoebic colonic perforation is difficult, especially in a non
      endemic area. Conservative surgical management is required in non-perforated
      forms. If perforated, the bowel must be resected, limited to macroscopic lesions.

PMID- 9035428
TI  - [Study of early postoperative lactitol versus paraffin following anal surgery in
      110 adult patients].
AB  - The aim of this open and randomised clinical trial was to compare, in terms of
      efficacy, lactitol with petroleum jelly, regarding the time before recovery of
      intestinal transit in patients having undergone anal surgery. Efficacy, comfort
      and tolerability were assessed on day 4 and 7, the convenience of treatments at
      the end of the period. The main criterion for efficacy was the time taken to
      obtain the first stool after surgery. Lactitol appears to be more effective than
      petroleum in terms of recovery of intestinal transit: the first postoperative
      stool was obtained 13 hours earlier with lactitol. This difference is
      statistically significant whatever the comparison: survival analysis (p = 0.0018)
      or t test on means (p = 0.0014). The secondary criteria for efficacy are
      consistent with this first result: the mean number of stools per day was
      significantly higher with lactitol (p = 0.046), the daily dose could be-reduced
      for more patients under lactitol on day 4 (p = 0.004) and, also on day 4, the
      general efficacy assessment was significantly in favour of lactitol (p = 0.033).
      The separate analysis of the items included in the comfort score shows that
      stools are more often "normal or soft" in the petroleum group and that pain on
      defecation is frequently less severe in the lactitol group. This led to a
      significantly higher comfort score in the petroleum group from D1 to D4 but not
      from D1 to D7. Tolerance was rated "good" by 97% of patients on day 7, and no
      statistically significant difference was observed for any of the tolerability
      criteria. Lactitol therefore appears to be an interesting choice, with a high
      benefit/risk ratio, in the treatment of the transitory constipation frequently
      observed immediately after anal surgery.

PMID- 9035429
TI  - [Ambulatory anal surgery: a feasibility study].
AB  - Because of the current economic situation, ambulatory surgery has become a "modus
      vivendi" for the surgeon. The aim of this study is to examine the feasibility of
      anal ambulatory surgery and the results obtained over a period of 12 months. 141
      consecutive patients underwent anal surgery: 108 on an ambulatory basis (77%) and
      33 were admitted to the hospital (23%). The reasons for admitting the patients
      were the complexity of the operation in 19 (8 sphincteroplasty, 5 complex
      fistulae, 3 recto-vaginal fistulae...) emergency procedures in 9 and
      miscellaneous reasons in 5 patients. All 108 patients operated on an ambulatory
      basis could be discharged at the end of the day but two, one for urinary
      retention and another because he underwent a more extensive procedure than first
      planned. Three more had urinary retention; they were catheterized and discharged
      on the same day. The four patients (3 women and 1 man) developed urinary
      retention following spinal anesthesia. Three patients (2.7%) had to come back to
      the emergency room in the first 24 hours for bleeding from the operative site.
      One of them had to be transfused and reoperated for hemostasis. In conclusion,
      ambulatory anal surgery is feasible in a large proportion of cases (77%) with a
      low rate of complications (7.4%) and low rate of unexpected hospital admission
      (2.7%). In a specialized colorectal unit, 23% of patients required
      hospitalization for a longer stay.

PMID- 9035430
TI  - [Comparison of hemodynamic and ventilatory effects of pneumoperitoneum using
      carbon dioxide or abdominal suspension during laparoscopic cholecystectomy].
AB  - This study compares the cardio-respiratory effects of CO2 pneumoperitoneum to
      those of abdominal suspension (or laparolift) in laparoscopic cholecystectomy.
      Between september 1993 et may 1995, 31 patients participated in this non
      randomized prospective trial. They consisted of 9 males et 22 females, with a
      mean age of 47.0 +/- 14 years. Sixteen patients were included in the CO2 group
      and 15 in the laparolift group. Both groups were comparable for age and gender.
      All patients were submitted to the same anaesthetic protocol. Repeated
      measurements of the respiratory and cardiovascular function were made during the
      intervention. End tidal CO2, minute ventilation, peak inspiratory pressure showed
      superior elevations in the CO2 group. And for the hemodynamic parameters, only
      the mean arterial pressure and cardiac frequency differed between the two groups,
      other hemodynamic parameters including left ventricular ejection fraction were
      comparable. Also, postoperatory hospital stay, OR time, per and postoperatory
      complications were comparable. With its stable hemodynamic and ventilatory
      pattern, abdominal suspension can constitute a safe and secure alternative to CO2
      pneumoperitoneum in patients with respiratory dysfunction.

PMID- 9035431
TI  - [Reduction of blood loss in orthotopic liver transplantation with the use of
      aprotinin].
AB  - The impact of aprotinin on blood losses during orthotopic liver transplantation
      (OLT) has been studied retrospectively. PATIENTS AND METHODS: From September 1984
      to July 1995, 152 patients underwent 168 OLT in our center. Seventy three
      patients (group I) received epsilon-aminocaproic acid as an antifibrinolytic
      agent and 95 patients (group II) received aprotinin. RESULTS: There was a
      significant reduction in the mean duration of the surgery (I = 743 +/- 25 min; II
      = 302 +/- 10 min; p < 0.001) and in the post reperfusion time (I = 282 +/- 13
      min; II = 126 +/- 6 min; p < 0.001) in the group II. The need for blood products
      during the operation was also reduced (blood units; I = 21.7 +/- 2.3 units; II =
      4.6 +/- 0.4 units; p < 0.001). There was less infectious and hemorrhagic
      complications requiring reoperation in group II. We have not seen an increased
      incidence of thrombotic complications in the patients receiving aprotinin. Other
      variables such as the use of hemoclips, veno-venous bypass and the type of
      preservation solution were also considered. CONCLUSION: Aprotinin use during OLT
      is efficient and superior to epsilon-aminocaproic acid in reducing blood losses.
      Combined with the non-utilisation of a veno-venous by-pass and the use of
      hemoclips, it helps reduce the operating time and the postoperative
      complications.

PMID- 9035432
TI  - [Peritoneal dialysis: peritonitis and catheter infections].
AB  - Infections were reviewed among 118 patients (M = 64, F = 54) undergoing
      peritoneal dialysis (PD) from 01-86 to 12-91. One hundred and fifty-five
      catheters were installed during the study period. Twenty-seven (23%) had more
      than one catheter. Forty-seven patients (39.8%) were diabetics. Mean follow-up
      was 460 days per catheter and 540 days per patient. Factors were collected and
      analyzed by multiple logistic regression. Survival curves were drawn according to
      the Kaplan-Meyer method. One year survival was 73.8%. Respective incidence of the
      different infections are presented. Fourteen percent of peritonitis, 48% of
      tunnel infections and 2.1% of exit site infections led to catheter removal.
      Younger patients had more catheter infections (p < 0.05). The different types of
      infections were significantly influenced by the system of dialysis employed (p <
      0.005). Perioperative antibiotic coverage diminished the incidence of peritonitis
      during the first three months (p < 0.05). With our data and our literature
      review, we have attempted to make some recommendations in order to reduce the
      occurrence of infections under PD.

PMID- 9035433
TI  - [Popliteal aneurysm: surgical treatment is mandatory before complications occur].
AB  - Between 1972 and 1995, surgical repair was undertaken for 94 popliteal aneurysms
      diagnosed in 71 patients (69 men and 2 women) with a mean age of 66 years. Ninety
      one femoropopliteal bypasses, 2 lumbar sympathectomies and one primary amputation
      were performed. Postoperative results of 28 elective bypasses performed for
      asymptomatic aneurysms (AA) were compared with 63 revascularisations needed for
      symptomatic aneurysms (SA) secondary to thrombosis (31%), embolization (30%),
      venous or nerve compression (13%), or rupture (2.1%). Occlusion of at least one
      tibial vessel was documented angiographically in 40% of the asymptomatic
      aneurysms and in 80% of the symptomatic aneurysms. No significant difference was
      observed between 5-year graft-patency of asymptomatic aneurysms (64%, mean
      followup 30 months +/- 37.2) and symptomatic aneurysms (50%, mean followup 39
      months +/- 40.9). Furthermore, 5-year graft patency was not influenced by the
      number of patent tibial vessels in either of these populations. No statistically
      significant difference between these two groups was observed with respect to
      morbidity (AA: 10.7%, SA: 19%), or early reintervention (AA: 7.1%, SA: 9.5%).
      However, 12 secondary amputations were needed, all of which were performed after
      repair of a symptomatic aneurysm (19%, p < 0.05). No postoperative mortality was
      observed after an elective bypass while 3 patients (4.8%) with symptomatic
      aneurysms died after an emergency surgery. Ischemic symptoms persisted in 56% of
      patients who were initially symptomatic. Surgical correction should therefore be
      performed once the diagnosis of a popliteal aneurysm has been established in
      order to prevent amputation and late sequelae.

PMID- 9035434
TI  - [Development of circulatory support during 420 aneurysm resections of the
      descending thoracic aorta].
AB  - From July 1974 to January 1996, 420 aneurysms of the descending thoracic aorta
      were surgically treated at l'Hopital du Sacre-Coeur de Montreal. Three principles
      were previously established and rigorously respected: 1) the preservation of
      distal body perfusion, 2) the briefest aortic cross-clamp time realizable (mean:
      29.8 +/- 16 minutes overall, reduced to a mean of 24 +/- 6 minutes for the last
      250 cases), 3) keep the aortic resection as short as possible in order to
      preserve as many intercostal arteries as possible (10 cm or less in 91.6% of the
      cases). In the first 380 cases, distal aortic circulation was supported with a 9
      mm Gott shunt without using systemic heparinization. Average shunt flows from 300
      ml/min, to 4900 ml/min. (mean: 2497 +/- 813 ml/min.), average proximal pressures
      from 80 to 200 mmHg (mean: 146 +/- 17 mmHg) and average distal pressures from 15
      to 150 mmHg (mean: 64 +/- 19 mmHg) were recorded. In the last 40 cases, the
      distal circulation was supplied through the left heart assistance device Bio
      Medicus using minimal systemic heparinization (0.5 mg/kg), (target ACT > 150
      seconds). Average pump flows from 1800 ml/min to 5200 ml/min. (mean: 3340 +/- 866
      ml/min.) were obtained. Average proximal pressures from 90 to 200 mmHg (mean: 118
      +/- 19 mmHg) and average distal pressures from 58 to 180 mmHg (mean: 95 +/- 24
      mmHg) were recorded. Overall hospital mortality is 11.9% (50/420 cases) and 9.9%
      when ruptured aneurysms are excluded. Paraplegia occurred in 2 patients (0.4%)
      and one was related to an unfunctional Gott shunt. Adverse anatomical conditions
      like a proximal aneurysm, degenerative changes of the aortic wall, a previous
      proximal graft replacement or the presence of coronary artery bypass grafts, a
      friable wall encountered with dissecting aneurysms and also an adverse
      physiological condition like a left ventricular dysfunction prompted us to modify
      the circulatory support by using the left heart bypass. Comparison of both
      methods of perfusion supported by statistical analysis regarding shunt and pump
      flows, proximal and distal perfusion pressures has showed the physiological
      superiority of the centrifugal pump that we have now routinely adopted.

PMID- 9035435
TI  - [Computer assisted pedicle screw installation. Our first 3 cases].
AB  - Pedicle screw fixation is sometimes a difficult surgical procedure relying on
      anatomical landmarks that may be modified by vertebral asymmetries. A significant
      incidence of cortex penetration and neuro-vascular complications have been
      documented. Our study evaluates the usefulness of a computer-aided pedicle
      installation system and analyses the results for our first 3 clinical cases. The
      system was used for 3 adolescent patients with idiopathic scoliosis undergoing
      surgical correction and instrumentation. In all cases, selected vertebrae were
      reconstructed in 3D pre-operatively. At surgery, the surgeon compared the
      computer-suggested pedicle location to his own opinion. After pedicular hole
      drilling was done in the usual fashion, hole positions were confirmed per
      operatively with the computer software. Post-operatively, software hole positions
      were measured and compared to the actual screw axis using CT-Scans. Three
      dimensional models produced for all selected vertebrae allowed visualization of
      asymmetrical deformations of the scoliotic vertebrae. All pedicles were correctly
      detected by the software. Pedicular hole measurements agreed with the actual
      screws positions on post-op CT-Scans. The computerized surgical assistant can be
      of value in a clinical situation. These initial results warrant a large scale
      trial in order to establish accuracy and reliability.

PMID- 9035436
TI  - [3-D evaluation of posture in normal and scoliotic adolescents].
AB  - We have developed a new clinical evaluation of the human posture based on 3D
      digitization with magnetic fields. This 3D postural evaluation displays the
      relative position of the head, the shoulders and the pelvis. The main purpose is
      to identify key morphological parameters in order to demonstrate significant
      differences between 2 groups of subjects. Nineteen adolescent control subjects
      and 22 patients with AIS have been evaluated. The t-tests showed significant
      statistical differences between the 2 groups for every measurements studied. The
      2 most significant were tilt of the shoulders in the postero-anterior plane and
      the angle of the shoulder-blades vs the shoulders in the transverse plane (p <
      0.0005). These results support the value of the 3D postural evaluation as a
      clinical tool for the evaluation of AIS. This technique is non-invasive and could
      be used for the clinical follow-up in order to evaluate the postural evolution in
      scoliotic patients.

PMID- 9035437
TI  - [Dorso-lumbal pain and idiopathic scoliosis in adolescence].
AB  - Current knowledge on the association between back pain and idiopathic scoliosis
      is often contradictory. The presence, localisation and importance of pain was
      evaluated for a cohort of 426 adolescents with AIS. Patients were recruited from
      a scoliosis clinic in a pediatric hospital. A questionnaire and an analogue
      visual scale graduated from 0 (no pain) to 100 (maximal pain) were used in order
      to verify more precisely, the importance of the association between AIS and back
      pain. Chisquare, linear regression and Student T-test were used for statistical
      analysis. 239 patients with right thoracic and left lumbar curves (RTLL) had a
      prevalence of pain of 54%. The mean of maximum pain intensity was 49 mm +/- 20.
      No relation was found between the severity of the scoliosis and back pain. The
      two groups (with and without pain) were comparable. Cobb angles were about the
      same for the thoracic and lumbar regions, as well as kyphosis and lordosis,
      weight, height and age. Risser sign, sex, brace and pelvic tilt were the only
      variables associated with pain (p < 0.0001). Association between AIS and pain is
      more frequent than generally reported. Pain appears to be more related with
      pelvic tilt than severity of the scoliosis.

PMID- 9035438
TI  - [A study of biomechanical coupling between spine and rib cage in the treatment by
      orthosis of scoliosis].
AB  - Orthoses are widely used to treat scoliotic deformities of the trunk, but the way
      the corrective forces are transmitted from the thorax to the spine remains not
      well understood, and several undesired effects such as the reduction of sagittal
      curvatures or weak derotations are often reported. A biomechanical finite element
      model of the trunk was used to investigate the hypothesis that there exist
      coupling mechanisms between the scoliotic spine and rib cage which may explain
      incomplete and unexpected results obtained by orthotic treatments. Forces of 40 N
      were applied on the rib hump and on the lateral side of the thorax, and their
      individual effects were evaluated in 3-D on the spine and thorax using several
      geometrical indices (transverse plane translations, axial, sagittal and frontal
      rotations, Cobb angles). These biomechanical simulations demonstrated the
      existence of coupled motions between the spine and rib cage subjected to orthotic
      loads. It showed that reduction of physiological sagittal curvatures (up to 30%)
      are possibly related to anterior orthotic loads applied on the rib hump. These
      loads also contribute to increase lateral shift of the spine (up to 7 mm) as well
      as scoliotic frontal curvatures (up to 4 degrees). Based on the results found in
      this study, a simple and more optimal approach to treat scoliotic deformities was
      proposed and consisted to apply loads laterally on the convex side and on the
      anterior thorax opposite to the rib hump, with a system that mechanically
      constrains the posterior rib hump to move backward. It was simulated on 4
      scoliotic patients presenting thoracic curves between 22 degrees and 54 degrees
      to evaluate its practicability and it was found that derotation of the trunk
      (between 7 degrees and 13 degrees) and reduction of frontal curvatures (up to 4
      degrees) could be done without reducing physiological sagittal curvatures. More
      simulations on different scoliotic configurations are necessary to find the most
      optimal combination of forces to produce a real 3-D correction of scoliotic
      deformities.

PMID- 9035439
TI  - [Bio-absorbable synthetic polyesters and tissue regeneration. A study of three
      dimensional proliferation of ovine chondrocytes and osteoblasts].
AB  - The tissue engineering area henceforth calls more and more for bioabsorbable
      substrata made of biopolymers (collagen, laminin...) or polymers (PLA, PLGA,
      PGA...) to realize the three-dimensional culture of tissue equivalents. The poly
      (beta-hydroxybutyrate-beta-hydroxyvalerate), a biopolymer considered as being
      biodegradable and biocompatible, has been recently introduced for orthopaedic
      biomaterials and regeneration purposes. In our study, a PHB/9% HV polymer was
      transformed into 3D foams, then applied to the culture 3D of ovine chondrocytes
      (fibrous rings & growth plates) and osteoblasts (periostum). Sponges made of
      bovine type I collagen were used as references. Orthopaedic cells were isolated,
      prepared and sown by simple injection to the geometrical center of the substrata,
      then incubated from 0 to 35 days by changing the culture medium all 4 days.
      Maximal densities were reached after 21 days: 18-24.10(6) cells/g for the
      chondrocytes, 8-10.10(6) cells/g for the osteoblasts. The cellular proliferation
      was more marked, with highest cell densities, for the collagen sponges. Laser
      confocal microscopy shows that the cellular diffusion take place throughout the
      entire volume of the porous artificial substrata. Future studies will allow to
      apply the porous bioabsorbable substrata to high-density cell cultures, to the
      tissue engineering and regeneration, for example for orthopaedic tissues:
      cartilage, fibrocartilage and bone.

PMID- 9035440
TI  - [A study of autonomic innervation of the atrial septum by iso-integral mapping in
      dogs].
AB  - Although neuronal cell bodies have been identified in the upper part of the
      atrial septum, the functional anatomy of its autonomic innervation remains
      unknown. To study parasympathetic inputs to the atrial septum, we performed
      isointegral distribution mapping using a 64-electrode balloon array inserted in
      the right atrium under cardiopulmonary bypass in 9 anesthetized mongrel dogs.
      Unipolar electrograms were recorded during stimulation of either the right or
      left vagus nerve or right atrialpulmonary vein ganglionated plexus before and
      after surgical ablation of tissues along the superior vena cava, of the right
      atrial-pulmonary vein ganglionated plexus, the aorto-pulmonary tissues and the
      inferior vena cava fat pad. Local neural effects were estimated from integral
      changes of each electrogram which were plotted on a septal grid to generate
      isointegral distribution maps. Changes were considered significant whenever
      integral differences exceeded twice the standard deviation of control values.
      Stimulation of the right and left vagi induced significant effects in the high
      atrial septum in 5 preparations and in the low septum in 6. These effects were
      suppressed by the dissection of tissues around the superior vena cava and
      ablation of the right atrial-pulmonary vein ganglionated plexus, but not by that
      of the inferior vena cava or the aorto-pulmonary tissues. Direct stimulation of
      the right atrial-pulmonary vein ganglionated plexus produced effects in the high
      and low septum in 8 and 4 preparations, respectively, which persisted after
      dissection around the superior vena cava, suggesting the existence of local
      circuit neural elements. We conclude that the canine atrial septum is innervated
      by axons from both vagi which course near the superior vena cava and converge
      through the right atrial-pulmonary vein ganglionated plexus and also by intrinsic
      neural elements independent of central parasympathetic efferents.

PMID- 9035441
TI  - [Effect of cyclosporin A dosage on the vascular tone of the thoracic aorta of
      rats].
AB  - Cyclosporine A (CyA) is known to affect the local release of endothelial-derived
      relaxing factor (EDRF). However, evidence that CyA could specifically alter
      endothelial signal transduction is not well understood. Experiments were designed
      to assess dose-dependent effect of CyA on vascular reactivity-specificity of the
      rat thoracic aorta. Three groups of rats (n = 10) were treated for 4 weeks with
      oral CyA 15 mg/kg/day (Gr 1), CyA 30 mg/kg/day (Gr 2), and olive oil (Gr 3), the
      CyA vehicle. At the end of the period, animals were euthanized and the thoracic
      aorta harvested for isometric assessment of endothelial and smooth muscle
      function in organ chambers. Maximal endothelial-dependent relaxation (Rmax) to
      acetylcholine dose-response was similarly affected in rats treated with CyA [Rmax
      (%): Gr 1: 33 +/- 8, Gr 2: 28 +/- 2, Gr 3:51 +/- 7, *p < 0.05]. At the opposite,
      response to adenosine diphosphate [Rmax (%): Gr 1: 11 +/- 2, Gr 2:24 +/- 3*, Gr
      3:7 +/- 2, *p < 0.01] and histamine [dose-response CE50 (log M): Gr 1: +/- 12 +/-
      0.05, Gr 2: +/- 5.45 +/- 0.05*, Gr 3: -4.85 +/- 0.08, *p < 0.05] were
      significantly enhanced in animals exposed to 30 mg/kg/day. Endothelium
      independent relaxation to sodium nitroprusside (SNP) was comparable in all groups
      and dose-response to depolarizing (KCl) and non-depolarizing (norepinephrine)
      contractile agents were not affected either. These experiments suggest that CyA
      does not affect second messenger (cyclic-GMP) activation by an EDRF analogue
      (SNP) whereas signal transduction coupled to muscarinic, purinergic, and
      histaminergic receptors are either inhibited or enhanced by CyA in dose-dependent
      manner in the rat aortic model.

PMID- 9035442
TI  - [Effect of vitamin E on the endothelial function of the regenerated aorta in rats
      following direct arterial injury].
AB  - Fibromuscular intimal injury is frequent after coronary or peripheral
      angioplasty. Peroxidation of circulating and membrane lipids have been implicated
      in intimal hyperplasia and endothelial dysfunction following direct arterial
      trauma. The aim of this study was to evaluate the effects of natural membrane
      antioxidant, vitamin E (VE), on the vascular reactivity of the regenerated
      endothelium. A first group of rats (n = 10) was pretreated with VE 100 IU/kg/day
      for a week before undergoing aortic (thoracic) endothelial denudation with a
      Fogarty catheter. Rats were then fed with the same VE supplemented diet for a 2
      month period. A second group (n = 10), was similarly denudated and fed with soya
      oil (SO), VE vehicle, for the same period. A third group (n = 10) was denuded and
      used as control (CL). Endothelial-dependent and independent relaxations were
      assessed in organ chambers with acetylcholine (ACH), adenosine diphosphate (ADP),
      histamine (HIS), 5-hydroxytryptamine (5-HT) and sodium nitroprusside (SNP).
      Endothelial regeneration was evaluated with Evans blue staining. Vascular
      relaxation to SNP was not affected either by the regeneration process or the VE
      supplementation. However, endothelial-dependent relaxation to ACH and HIS were
      significantly impeded in the regenerated endothelium compared to control but was
      not influenced by the VE or the SO supplementation. Vascular contraction to 5-HT
      was significantly decreased in VE group compared to the other groups.
      Morphometric studies with Evans blue staining showed over 95% regeneration of the
      endothelial surface of the denuded aortas. Our results suggest that in spite of a
      complete anatomical regeneration, endothelial cells did not resume predenudation
      function. Endothelial-independent relaxation was preserved in all groups
      indicating that smooth muscle function was not altered by the regenerating
      process. The presence of dietary supplement of VE (up to 20 fold the daily
      requirement) did not prevent the endothelial dysfunction to ACH and HIS but
      attenuated the vaso-contraction to 5-HT and then could contribute to decreased
      vascular tone in endothelium-regenerated vessels.

PMID- 9035443
TI  - [Effect of cyclosporin A on the reactivity of the pulmonary vascular network in
      dogs].
AB  - Aside to its immunosuppressive effects, cyclosporine A (CyA) is known as a
      vasoconstrictor agent. The vasoconstriction appears to be related to an
      endothelial release of thromboxane A2 (TxA2) and endothelium as well as a
      decrease endothelial production of nitric oxide. However, no data is available on
      the effects of CyA on pulmonary artery (PA) network. We designed experiments to
      study the CyA effects on canine pulmonary artery vasoregulation. Resistance
      vessels were studied in vivo using a lung (n = 6) steady rate delivery
      autoperfusion model. The CyA was infused in the left pulmonary artery at
      incremental doses of 5, 10, and 20 mg; CyA dosage, sampled in the left atrium,
      were respectively 515 +/- 67, 580 +/- 97, and 1024 +/- 84 nmol/L. No significant
      increase in tension were registered regardless of the dose infused. Conductance
      vessels were studied in vitro using third division PA segments (n = 6) suspended
      for isometric force measurement in organ chambers. PA segments were precontracted
      (phenylephrine 10(-6) M) and subsequently exposed to incremental dose of CyA and
      cremophor (CR), the CyA vehicle. CyA specifically induced a dose-dependent
      contraction. The maximal contraction observed were 159 g +/- 13% with CyA
      exposure and 106 +/- 3% with the CR (p < 0.05). This contraction was abolished by
      indomethacin (cyclooxygenase inhibitor), pinane thromboxane A2 (TxA2 antagonist),
      dexamethasone (phospholipase A2 inhibitor), neomycin (phospholipase C inhibitor),
      and endothelial mechanical denudation. CONCLUSIONS: In the canine model, in vivo
      infusion of CyA does not affect pulmonary resistance arteries. However, in vitro,
      on pulmonary conductance arteries, CyA induces an endothelium-dependent
      vasoconstriction. This constriction appears to be related to a TxA2 release
      mediated by a phospholipase A2 phospholipase C pathway.

PMID- 9035444
TI  - [Effect of the ventricular preload on the basal and stimulated coronary
      circulation of the isolated rat heart].
AB  - Langendorff perfused isolated rat heart is a common model for coronary blood flow
      study. Left ventricular preload can both increase coronary blood flow by direct
      inotropic effect or decrease it by rising transmural tension. Experiments were
      designed to determine optimal preload conditions for observation of basal (CBF)
      and 5-hydroxytryptamine (5-HT) stimulated coronary blood flow (SCBF) in the
      isolated rat heart model. Rat hearts (n = 6) were harvested and stabilized in the
      Langendorff apparatus and a left ventricular balloon was inserted and inflated at
      different volumes (0.05 to 0.4 ml) to stimulate preload. Left ventricular
      systolic (LVSP), diastolic (LVDP), myocardial oxygen consumption (MVO2) and
      extraction (MEO2) were also measured. Under basal conditions, optimal LVSP was
      obtained at 0.2 ml (111 +/- 15 mmHg). MVO2 was optimal at 0.2 ml of preload and
      decreased thereafter while MEO2 remained stable. Optimal CBF was reached at 0.2
      ml of preload. Under 5-HT stimulation, CBF increased significantly (CBF: 8.2 +/-
      0.6 ml/min vs SCBF: 16.4 +/- 1.0 ml/min, p < 0.01) while left ventricular
      hemodynamics did not differ from basal observations. At preload volume > 0.2 ml a
      significant drop in SCBF was observed (0 ml: 16.4 +/- 1 ml/min vs 0.4 ml: 11 +/-
      1 ml/min, p < 0.01). MVO2 and MEO2 followed the same pattern observed under basal
      conditions. In basal and stimulated conditions, a hyperemic flow was also seen
      after deflation of the balloon with preload > = 0.2 ml in both CBF and SCBF
      suggesting myocardial oxygen debt. We conclude that in the Langendorff model
      preload affects coronary flow under both basal and 5-HT stimulation. A volume >
      0.2 ml for rats of 350-400 g can impede CBF and generate myocardial oxygen debt
      as suggested by a decreased MVO2 and a post-deflation hyperemic flow. Left
      ventricular preload should be maintained under 0.2 ml for optimal coronary blood
      flow study in the Langendorff perfused rat heart model.

PMID- 9035445
TI  - [Pubertal development after pediatric heart transplantation].
AB  - Twenty-one children and adolescents underwent orthotopic cardiac transplantation
      at the Hopital Sainte-Justine between July 1984 and June 1993. Of those patients,
      16 (4 girls and 12 boys) who survived more than one year after the procedure were
      followed prospectively for documentation of onset and progression of puberty. The
      immunosuppressive therapy included cyclosporine, azathioprine and prednisone.
      Subjects were evaluated at 6 month intervals for the study of: pubertal
      development according to staging by the method of Marshall and Tanner and
      hormonal profile (FSH, LH, testosterone, DHEAS). Despite a stagnation of pubertal
      signs before surgery, puberty carried on and progressed normally postoperatively.
      The urinary levels of gonadotropins rose to adequate levels for age. Testosterone
      levels in boys were related to the progression of secondary sexual
      characteristics. Levels of DHEAS were drastically reduced, most likely because of
      the supraphysiological doses of oral glucocorticoids. Our results indicate that
      after pediatric heart transplantation, puberty progresses normally at
      adolescence.

PMID- 9035446
TI  - [Pulmonary valve replacement in children].
AB  - From February 1988 to October 1994, 15 pulmonary valve replacements (PVR) have
      been performed at St-Justine Hospital in children with a mean age of 145.7
      months. Ten children previously had a correction of tetralogy of Fallot; two had
      absent pulmonary valve syndrome; one had been operated on for pulmonary atresia
      with intact ventricular septum, one other had a correction for a ventricular
      septal defect with pulmonary artery banding; the last patient developed
      degeneration of a pulmonary bioprosthesis. The time between the primary repair
      and the PVR ranged from 61 to 221 months. Fourteen bioprosthesis and one aortic
      homograft were implanted. All patients had antiplatelet treatment. There was one
      operative death due to a fatal anaphylactic reaction and one late death occurred
      unrelated to valvular surgery. At follow-up from 1 to 187 months (mean, 40.7
      months) all patients were in New York Heart Association Class 1. No hemorrhagic
      nor thromboembolic complication have been observed and no reoperation for
      bioprosthesis failure was necessary. Nevertheless in subsequent echocardiographic
      studies, two patients with the smallest bioprosthesis (21 mm) have developed
      pulmonary gradients of 80 and 85 mmHg, 65 and 80 months following PVR. While our
      results with PVR in children have been satisfactory, this operation should be
      performed only in symptomatic patients with severe pulmonary regurgitation
      because of progressive deterioration of the available bioprosthesis.

PMID- 9035447
TI  - [Tricuspid valve replacement: long-term clinical and echocardiographic follow
      up].
AB  - Long term results of tricuspid valve replacement, were evaluated by
      echocardiographic and clinical means retrospectively on 55 patients hospitalized
      at the Montreal Heart Institute between 1969 and 1993. Twenty seven percent were
      male and 73% female. Taking into account differences in means of myocardial
      protection the whole population was divided in 2 groups. Group 1: 19 patients
      from 1969 to 1980. Group 2: 36 patients - from 1981 to 1994. Forty seven patients
      (85%) received a bioprosthesis and 8 (15%) a mechanical valve. Forty one (74%)
      had another surgical procedure and 60% (33 patients) were re-operations.
      Mortality at 30 days is 23% (13 patients) -15% group 1 and 27% group 2. Twenty
      six patients (72%) of group 2 were re-operations compared with 7 (36%) for group
      1 (p = 0.026). Risk factors of operative mortality were: high systolic pulmonary
      pressure (0.051), bypass time (0.012) and abnormal ejection fraction (0.025).
      Mean time of follow up is 113.8 months completed at 95%. Six patients were re
      operated; 4 for failure of bioprosthesis 11.5 years (mean) after initial surgery.
      Forty three percent of patients presented with an amelioration of NYHA class. 26%
      in class I and 50% in class II. Mean gradient across the tricuspid valve was 4.1
      +/- 1 mm Hg. Twenty two over 42 patients (50%) died during follow up: 75 months
      after surgery.

PMID- 9035448
TI  - [The history of cardiac surgery].

PMID- 9035449
TI  - [Precision and accuracy of blood lipid analyses by a portable device (Cholestech
      LDX)].
AB  - PURPOSE: To verify whether precision and accuracy of lipids analyses by a new
      portable device, Cholestech-lipid desktop analyzer (LDX), were in agreement with
      the guidelines of the National Cholesterol Education Program (NCEP). METHODS:
      Serum samples from 45 outpatients were collected for the determination of total
      Cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG). These samples
      were analysed simultaneously by the Cholestech-LDX, and by the automatic
      enzymatic methods routinely used at the Heart Institute's laboratory. Precision
      was determined by repeating 20 times the evaluation of the same sample of venous
      blood. Accuracy was established confronting the values of the lipids variables
      obtained with Cholestech-LDX against the values determined by the automatic
      enzymatic routine. RESULTS: Accuracy for TC was 1.60% (NCEP < or = 3%), for HDL-C
      was -2.74% (NCEP < or = 6%) and for TG was 2.11% (NCEP < or = 5%). Precision for
      CT was 3.05% (NCEP < or = 3%), for HDL-C was 1.05% (NCEP < or = 6%) and for TG
      was 2.65% (NCEP < 5%). CONCLUSION: Precision and accuracy of lipids evaluation by
      the Cholestech-LDX are within the guidelines of the National Cholesterol
      Education Program. Therefore the cholestech-LDX seems to be a reliable
      alternative to the conventional biochemical routine, allowing population
      screenings.

PMID- 9035450
TI  - [Different therapies in the treatment of obesity in hypertensive patients].
AB  - PURPOSE: To evaluate the efficacy and tolerability of different therapies
      associated with diet in the treatment of hypertensive obese patients. METHODS: In
      a clinical study we randomly evaluated 39 hypertensive obese patients (body mass
      index (BMI) > or = 30 kg/m2). After 45 days of diet the patients were again
      randomly distributed in 3 groups and received in double blind way: group 1
      hypocaloric diet+placebo; group 2-hypocaloric diet+dexfenfluramine; group 3
      hypocaloric diet+spiruline+fucus+gelatin. We followed their progress during 12
      weeks under medication and further 24 weeks without. We evaluated the groups
      comparing: weight, BMI, blood pressure and side-effects. RESULTS: Twenty seven
      patients completed the observation. In those patients from groups 1 and 3 no
      changes in any of parameters were observed. In group 2 we observed a clear loss
      of weight (-3.8 Kg) and a fall in BMI. Blood Pressure changes were only observed
      in group 2 (-9.6%). The only patients to maintain weight loss after the
      termination of use of medicines were those from group 2. We did not observe any
      side-effects. CONCLUSION: In hypertensive obese patients, when isolated diet is
      not enough to control weight loss, dexfenfluramine could be useful in association
      with a controlled diet. The drug assists in weight loss, does not promote side
      effects and does not interfere in the treatment of blood pressure.

PMID- 9035451
TI  - [Immediate and late results of the surgical treatment of the aneurysms and
      dissections of the ascending aorta].
AB  - PURPOSE: To report our experience and results with the surgical treatment of
      aortic aneurysms and dissections of the ascending aorta as well as the techniques
      that have been used. METHODS: Between May 1982-May 1995, 54 patients were
      operated on and divided in two groups: group A was composed of 25 patients with
      aneurysms or chronic dissections of the ascending aorta. The Bentall and DeBonno
      procedure was performed in 18, five were submitted to prosthetic aortic graft
      associated with aortic valve replacement and two prosthetic aortic graft without
      aortic valve replacement. Group B had 29 patients with acute dissections of the
      ascending aorta (type A) who were submitted to 10 prosthetic graft alone, nine
      Bentall procedures, five prosthetic graft with aortic valve replacement, four
      aortic repair and one direct suture of the dissection. The survival curve was
      obtained by the Kaplan-Meier method. RESULTS: Total hospital mortality rate was
      13% and the late was 18.5%. Group A-immediate mortality rate was 8% (two
      patients): Low cardiac output and stroke; late mortality rate was five (20%):
      sudden death in three, pulmonary embolism one and infectious endocardite one.
      Group B-hospital mortality rate was five (17.2%) patients: low cardiac output
      three, multiple organs failure one and stroke with pneumonia one; late mortality
      rate was five (17.2%), distal redissection in three, sudden death in two. The
      average survival time was 86 +/- 12 for group A and 75 +/- 13 months for group B.
      CONCLUSION: The surgery of the aneurysm and dissections of the ascending aorta
      has shown immediate favorable results and a thorough follow-up to get better late
      results is needed.

PMID- 9035452
TI  - [Massive pulmonary arteriovenous fistula. A rare, potentially curable cause of
      hypoxia in the newborn].
AB  - The case of a six-day-old neonate admitted in an emergency situation because of
      dyspnea and increasing cyanosis is reported. Despite abnormal opacification on
      the chest X-ray and left ventricular overload on the electrocardiogram and
      echocardiogram, features compatible with the disease, the diagnosis of massive
      pulmonary arteriovenous fistula affecting the whole left superior lobe, was made
      possible only after necroscopic examination.

PMID- 9035453
TI  - [Coronary artery perforation with rotational coronary atherectomy].
AB  - The authors describe a rare case of circumflex coronary artery perforation during
      rotational coronary atherectomy complicated with cardiac tamponade and good
      outcome. The possible causes of perforation are discussed and the burr oversize
      (burr/artery ratio was 0.58) was refused. Shortening and artery plicature
      (accordeon effect) might have been the cause of this event. Quantitative
      measurement was made in order to strengthen this hypothesis. It is emphasized the
      importance of selecting lesions that should be submitted to rotational coronary
      atherectomy.

PMID- 9035454
TI  - [Intrapericardial teratoma. A case report and a literature review].
AB  - A case of newborn intrapericardial teratoma is reported. The clinical,
      echocardiographic, tomographic and histologic features are described, and also,
      the therapeutic options. The newborn was submitted to surgical excision of the
      intrapericardial tumor and has a clinical follow-up greater than four years.

PMID- 9035455
TI  - [Treatment of mild and moderate hypertension with diltiazem 240mg. Brazilian
      multicenter trial].
AB  - PURPOSE: The efficacy and safety of diltiazen 240mg was evaluated in essential
      hypertensive patients with diastolic pressure in the range of 95 to 115 mmHg.
      METHODS: In an open, non-comparative multicenter trial 2.165 hypertensives had
      the supine and orthostatic arterial blood pressure measured before, after 14 days
      with non pharmacologic therapy and after 40 days taking diltiazen 240mg/day.
      Also, the serum levels of lipids, glucose and electrolytes were measured before
      and after the use of the active drug. RESULTS: The systolic arterial pressure in
      the first day was 166 +/- 18mmHg, in the 14th day was 155 +/- 20mmHg; and, in the
      54th day was 141 +/- 14mmHg (p < 0.05). Also, supine and orthostatic diastolic
      blood pressure was lower in the 14th and in the 54th days when compared to
      baseline (p < 0.05). Cholesterol, triglycerides, urea and uric acid levels
      decreased significantly (p < 0.05) during treatment. CONCLUSION: This study
      demonstrates that diltiazem 240mg/day for the treatment of hypertension is well
      tolerated, efficient and shows no metabolic undesirable effects.

PMID- 9035456
TI  - [Nicotine. Actions and interactions].

PMID- 9035457
TI  - [National Consensus on Cardiorespiratory Resuscitation].

PMID- 9035458
TI  - [Normal maximal functional capacity in patients with congestive heart failure due
      to Chagas' cardiomyopathy].
AB  - PURPOSE: To compare patients with heart failure due to Chagas' cardiomyopathy and
      maximal oxygen consumption greater than 20mL/kg-1/min-1 to normal individuals.
      METHODS: We studied 104 male patients with heart failure due to Chagas'
      cardiomyopathy, functional classe II-IV, age 18 to 65 years (40.3 +/- 9.0), and
      23 normal sedentary male individuals (GI) age 17 to 51 years (35 +/- 8.7).
      Maximal oxygen consumption (VO2max) was obtained using a Beckman metabolic
      measurement cart, and left ventricular ejection fraction (EF) by conventional
      transthoracic echocardiography. Comparisons between means were made with t-test.
      RESULTS: Thirty seven patients (35.6%) presented VO2max above 20mL/kg-1/min-1
      (G2), with values ranging from 20.5 to 30 (24.5 +/- 2.9) and EF between 19 and
      63% (42 +/- 11.7). GI had VO2max between 21 and 42mL/kg-1/min-1 (33.3 +/- 5.6)
      and EF between 70 and 82% (75.1 +/- 3.2). Ages were not significantly different
      for the two groups (p = 0.1136). VO2max and EF were lower in G2, and this was
      statistically significant (p < 0.0001). CONCLUSION: These results indicate that
      patients with congestive heart failure due to Chagas disease may show values of
      VO2max, greater than 20mL/kg-1/min-1 which does not mean that they have normal
      maximal functional capacity.

PMID- 9035459
TI  - [Effects of rejection on the contractile reserve of the graft after heart
      transplantation].
AB  - PURPOSE: To test the hypothesis that rejection could affect the contractility and
      contractile reserve of left ventricle after heart transplantation. METHODS:
      Echocardiographic parameters and noninvasive blood pressure end-systolic pressure
      (ESP), heart rate (HR), end diastolic (EDV) and end-systolic (ESV) volumes,
      ejection fraction (EF), end-systolic stress (ESS) and the end-systolic relation
      (ESS/ESV) were recorded in 68 studies in 11 patients, seven days-12 months after
      heart transplantation. Accordingly with the endomyocardial biopsies results were
      divided into two groups: group A-with no rejection (53 studies), and group B-with
      rejection (15 studies). RESULTS: The nitroprusside infusion changed significantly
      and in the same way, all the parameters except the ESS/ESV ratio (A = 5.5 +/- 1.7
      x B = 4.8 +/- 1.5 g/cm2/mL, p = NS); there was a decrease in ESP (A = 107 +/- 15
      and B = 109 +/- 12 mmHg, p = NS), EDV (A = 68 +/- 19 and B = 81 +/- 12 mL, p =
      NS), ESV (A = 12 +/- 5 and B = 18 +/- 12 mL, p = NS) and ESS (A = 59 +/- 13 and B
      = 82 +/- 20g/cm2, p = NS); there was an increase in HR (A = 94 +/- 9 and B = 93
      +/- 16bpm, p = NS) and EF (A = 83 +/- 5 and B = 79 +/- 8%, p = NS). In the
      dobutamine study it was observed differences for both groups, except for ESP (A =
      156 +/- 26 and B = 149 +/- 26mmHg, p = NS). The increase in HR, EF and ESS/ESV
      ratio was greater in group A (HR-A = 117 +/- 19 and B = 102 +/- 25bpm, p < 0.05;
      EF-A = 91 +/- 4 and B = 78 +/- 11%, p < 0.05; ESS/ESV-A = 13.1 +/- 6 and B = 6.1
      +/- 3.1 g/cm2/mL, p < 0.05). For group A it was smaller the EDV (57 +/- 18 x 94
      +/- 35 mL, p < 0.05), ESV (5 +/- 3 x 24 +/- 20 mL, p < 0.05) and ESS (57 +/- 21 x
      102 +/- 40 g/cm2, p < 0.05). CONCLUSION: Rejection may not induce changes in
      resting left ventricular contractility, however, the contractile reserve is
      depressed during an episode of moderate to severe rejection.

PMID- 9035460
TI  - [Intrauterine and perinatal management of complete atrioventricular block in the
      fetus].
AB  - PURPOSE: To report the experience of one of the most severe fetal rhythm
      disturbances, the complete atrioventricular block. METHODS: Descriptive study of
      14 fetuses diagnosed and monitored at the Fetal Cardiology Unit, from January,
      1991 to August, 1995. RESULTS: Fourteen cases of complete AV block were
      identified during the study period, with post-conceptional age between 22 and 38
      weeks at the moment of diagnosis. Twelve cases were referred to the Fetal
      Cardiology Unit because of low heart rate during obstetric examination. Eight
      fetuses showed complete AV block without evidence of structural heart disease;
      maternal collagen tissue disease was diagnosed in three of these cases. Four
      neonates were discharged from the hospital, two of them with a permanent
      pacemaker, one with complete AV block but no pacemaker and the fourth with sinus
      rhythm. The remaining seven neonates presented with severe heart failure leading
      to death despite treatment. CONCLUSION: Complete AV block is a rare fetal
      condition, but carries a high morbidity and mortality. A several treatment
      techniques have been suggested to improve monitoring and survival of these
      patients, particularly in utero.

PMID- 9035461
TI  - [Atrial septal defect percutaneous transvenous occlusion with the buttoned
      device].
AB  - PURPOSE: To analyse the experience with the use of Sideris' device for
      percutaneous transvenous occlusion of atrial septal defect (ASD). METHODS: Thirty
      six procedures of ASD occlusion were performed in 32 patients; 27 (84.4%) female
      and five (15.6%) male, mean age of 16 years (4-61). All patients had secundum
      atrial septal defects with clinical and hemodynamic compromise. The ASD diameter
      measured < 31 mm and occupied less than 50% of the septal length in all cases.
      The basic device was used in 28 (87.5%) patients and the self centered model in
      four (12.5%). The direct implant technique was employed in 15 (41.7%) procedures
      while in the other 21 (58.3%) an over a wire technique was used. The size of the
      device was selected according with the Sideris' normogram. RESULTS: Occlusion of
      the defect was achieved in 29 patients (90.63%). In two (6.25%) the position of
      the device was not adequate and in one (3.12%) the device embolized to the
      pulmonary artery. In these three cases the device was removed surgically during
      the defect closure. There was neither morbidity nor mortality in this series.
      Trivial or small residual shunt was detected with color flow mapping in three
      (9.4%) patients immediately after the procedure. In 22 patients with 12 months
      follow-up, trivial residual shunt was present in only one (4.5%). Structural
      modification of the device was detected in one patient, however with complete ASD
      occlusion and neither clinical nor hemodynamic disturbance. CONCLUSION: The
      Sideris' device is safe and efficient for ASD occlusion in selected patients.
      Although there is a relatively high incidence of residual shunt immediately after
      the procedure, the shunt itself tends to become smaller or disappear during the
      follow-up and it does not preclude clinical and hemodynamic improvement.

PMID- 9035462
TI  - [Patent ductus Arteriosus closure with Gianturco coils].
AB  - PURPOSE: To report our experience with PDA closure with Gianturco coils. METHODS:
      Between September 1995 and January 1996, nine patients underwent cardiac
      catheterization to have patent ductus arteriosus occlusion by Gianturco coils.
      Selection criteria were age > or = 6 months and narrowest PDA internal diameter <
      4 mm. 4F to 6F Judkins right coronary catheters were used to deliver the coils.
      One loop was delivered in the pulmonary artery and two loops delivered in the
      descending aorta across the ductus. Angiography after the procedure confirmed
      complete closure. Follow-up after coil placement occurred the next day, one month
      and three months by means of color flow mapping. RESULTS: Of the nine patients,
      seven had successful implants. In one no coil was delivered. In the first
      patient, there is a small residual shunt visualized by color flow doppler that
      persists after three months of the implant. One patient received two coils, other
      received three coils and the remainder received one coil each. There were no coil
      migration, or significant complication related to the implants. CONCLUSION: The
      coil occlusion of the ductus is a safe, effective and low-cost procedure, and
      should be included among non surgical technics of ductal closure.

PMID- 9035463
TI  - [Heart catheterization as present option in the treatment of congenital heart
      defects].

PMID- 9035464
TI  - [Anatomo-clinical correlation. Case 3/96 (Instituto do Coracao do Hospital das
      Clinicas-FMUSP)].

PMID- 9035465
TI  - [Diagnosis in pediatric cardiology. Clinical elements aren't obsolete].

PMID- 9035466
TI  - [Acute toxic actions of mercury on the cardiovascular system].

PMID- 9035468
TI  - [Exercise test in recent evolution of myocardial infarction].

PMID- 9035467
TI  - [Comparative effects of captopril and chlorthalidone on glucose tolerance and
      insulin levels essential hypertensives].
AB  - PURPOSE: To compare the effects of chlortalidone (CL) and captopril (Cp) upon
      glucose tolerance and serum insulin levels in essential hypertensive patients.
      METHODS: Non obese essential hypertensive patients with normal glucose tolerance
      test (OGTT) and diastolic blood pressure (DBP) > 90 mmHg and < or = 115 mmHg in
      the seated position were treated, in a randomized fashion, with Cp or CL during
      16 weeks, after 16 weeks of placebo. The OGTT was performed after placebo and
      after active therapy, with serum insulin levels determinations carried out before
      and 120 minutes after oral glucose load. RESULTS: Twenty four patients in the CL
      group and 19 in the Cp concluded the study. Hypocalemia (serum potassium <
      3.8mEq/L or serum potassium reductions > or = 0.9mEq/ L) occurred in nine
      patients of the CL group (CL H). In this group CL therapy induced increments in
      the area under the curve of glycemia during OGTT (582 vs 610mg/h/dL, p < 0.05)
      that were not observed in the normocalemic patients of the CL (CLN) or Cp groups.
      Serum insulin levels during OGTT did not change with active therapy in all three
      groups. The insulin sensitivity index, however, decreased significantly in the
      CLH (1.9 vs 1.4; p < 0.05) and CLN (10.1 vs 4.3, p < 0.05) but remained unchanged
      in the Cp group (3.1 vs 2.5; NS). The insulin response to glucose index increased
      in the Cp (0.28 vs 0.40; p < 0.05) group but not in the CLH (0.25 vs 0.42; NS)
      and CLN (0.07 vs 0.24). CONCLUSION: The antihypertensive therapy with
      chlortalidone in essential hypertensive patients may result in reductions in the
      peripheral sensitivity to insulin that can be accompanied by increases in
      glycemic levels after oral glucose load, particularly in patients who develop
      hypocalemia. Our results indicate that Cp therapy induces increments in insulin
      response to glucose without detectable changes in peripheral insulin sensitivity.

PMID- 9035469
TI  - [Ergometric test after surgical revascularization and mechanical recanalization
      of the myocardium].

PMID- 9035470
TI  - [Ergometric test in prognostic evaluation after acute myocardial infarction].

PMID- 9035471
TI  - [Use of the ergometric test at supporting clinical decision].

PMID- 9035472
TI  - [Responsibility and deontology of the medicolegal expertise].

PMID- 9035473
TI  - [The expert facing medical hazard].

PMID- 9035474
TI  - [The Medical Council and expertise on surgical responsibility].

PMID- 9035475
TI  - [Etiological and clinical evaluation of low acute respiratory infections in
      children].
AB  - Viral laboratory diagnosis was correlated with clinical and epidemiological data
      from 80 hospitalized children with acute lower respiratory infection (ALRI). They
      all were less than 5 years-old and were studied from May to September 1993.
      Fifteen percent of them were malnourished and 75% had some unsatisfied basic
      necessity. Nasopharingeal aspirates were obtained the first day of
      hospitalization, and diagnosis for respiratory viruses was performed by the
      immunofluorescence test with monoclonal antibodies. Routine laboratory
      determinations, x-ray studies, and clinical data were not conclusive to determine
      viral etiology. Forty-one percent of the children had a positive viral diagnosis:
      the most important agent was Respiratory Syncytial Virus (78.7%) followed by
      Adenovirus (9.1%), Influenza A (6.1%) and Parainfluenza (3%). The peak of
      incidence was observed in June and the majority of the patients remained
      hospitalized less than 10 days. Six children died: two of them had viral
      pneumonia and could not receive mechanical respiratory assistance. The percentage
      of children who received antibiotics was high, 61.2%, in spite of the fact that
      34.7% of these patients had a laboratory confirmed viral etiology. The
      availability of rapid laboratory viral diagnosis may contribute to decrease the
      use of antibiotics and improve the management of patients.

PMID- 9035476
TI  - [Differences between smear positive and smear negative pulmonary tuberculosis].
AB  - The decision related to treatment initiation in smear-negative pulmonary TB is
      controversial. To determine differences between the characteristics of smear
      negative, culture-positive pulmonary TB (Group D-) cases, we compared them with
      those patients who presented positive smear microscopy and cultures (Group D+).
      In addition, we compared the characteristics found in Group D- cases, in whom the
      treatment was started before confirmation by culture (sub-group D-TI) with those
      who were treated only after a positive culture was obtained (subgroup D-TD). We
      compared 270 patients of Group D+ with 48 of Group D-. The subgroups of Group D-
      (D-TI and D-TD) were compared with Group D+. Clinical symptoms, history, X-rays,
      other lung diseases and related extrapulmonary diseases were analysed Significant
      differences between groups D+ and D- related to age, history, X-rays and other
      lung diseases were found. There were no significant differences between Group D+
      and subgroup D-TI, except for the age. The same and even more accentuated
      differences between Group D+ and D- were found between Group D+ and subgroup D
      TD. CONCLUSIONS: Group D- was divided into to subgroups: D-TI, similar to D+,
      determined the decision to immediately start the treatment and D-TD, completely
      different; other possible diagnoses were considered and decision of treatment was
      delayed until a positive culture was obtained. This conduct proved to be the
      correct one in these cases where the diagnosis by culture was available.

PMID- 9035477
TI  - [Differential diagnosis between exudate and transudate in pleural effusion].
AB  - The objective was 1) to determine the usefulness of different criteria in the
      differential diagnosis between exudate and transudate in pleural effusion, 2) to
      evaluate albumin gradient changes in pleural effusion fluids characterized as
      transudates in patients who do and do not receive diuretic therapy, 3) to define
      the specificity of pleural effusions of neoplastic etiology. All patients with
      pleural effusion admitted to the hospital between January 15 and August 15 1994
      were evaluated consecutively. Serum and pleural effusion, total protein, LDH,
      albumin and cholesterol levels were measured and the etiologic diagnosis of the
      pleural effusion (gold standard) was established. Out of the total of 112
      evaluated patients, 7 were excluded because it was impossible to reach a final
      diagnosis. Based on the etiologic diagnosis, 47 patients (44.8%), average age of
      69.6 +/- 12.07, had pleural effusions defined as transudate and 58 patients
      (55.2%), average age of 66.5 +/- 14.26, had pleural effusions defined as exudate.
      Sixty-six percent of the transudates were secondary to heart failure, while 40%
      of the exudates were of neoplastic origin. Using the criteria of Light et al, we
      obtained a diagnostic accuracy (DA) of 82.7% (CI 95% 73.1-90.0)%. However, when
      the cut-off point was modified according to Valdez and the value of cholesterol
      in pleural effusion and its relation to serum cholesterol was added, the DA rose
      to 90.2 (83.2-96.0)% (p < 0.05). The effusion-serum cholesterol ratio
      demonstrated 100 (85.1-100)% sensitivity for neoplastic effusions, whereas for
      non-neoplastic exudative effusions the sensitivity was 89 (73.2-96.8)%. The
      tests, however, showed only 17.4 (6.56-33.6)% specificity. The albumin gradient
      (the difference between serum and pleural effusion albumin) did no vary in
      patients with transudates who received diuretics, allowing a correct diagnosis of
      transudate in 93 (82.4-97.8)% of the cases. However, in patients who were taking
      diuretics, the classic criteria of protein index defined correctly only 66 (53.4
      82.1)% of the cases (p < 0.05). It can be concluded that the variation of cut-off
      points originally established by Light et al. and the addition of cholesterol
      determination in pleural effusion and its relation to the serum cholesterol level
      allowed us to increase the DA. This appears to be the best way to differentiate a
      transudate from an exudate. The relation between pleural effusion and serum
      cholesterol levels showed a very low specificity for the differentiation of
      neoplastic and non-neoplastic exudative pleural effusions. Unlike the pleural
      effusion-serum total protein ratio, the albumin gradient allowed us to establish
      the correct diagnosis of transudate even in patients taking diuretics.

PMID- 9035478
TI  - [Mechanisms involved in the antiarrhythmic and proarrhythmic effects of
      magnesium].
AB  - This paper reports an electrophysiological study on the antiarrhythmic and
      proarrhythmic actions of magnesium chloride and magnesium sulphate intravenous
      infusions. Magnesium kinetics in control dogs, following a pulse of magnesium
      chloride or magnesium sulphate, was not affected by the accompanying anion. The
      experiments were performed with mongrel dogs divided into three groups fed either
      a normal diet (group I), a low magnesium diet plus chlortalidone treatment and
      potassium supplementation (group IIA) or a low magnesium diet plus chlortalidone
      treatment and magnesium sulphate infusion (group II B). In group I, infusion of
      magnesium sulphate solution decreased plasma sodium, potassium and ventricular
      fibrillation threshold (VFT), prolonged the ventricular effective refractory
      period (VERP) and increased the urinary excretion of potassium. The infusion of
      magnesium chloride solution did not affect VFT, prolonged VERP, QTc, AH and PQ.
      In this group, sodium chloride or sulphate infusion did not affect the
      electrophysiological variables but sodium sulphate decreased plasma potassium
      levels. The group II A was characterized by the decreased levels of potassium and
      magnesium contents of plasma, lymphocytes and myocardium, decreased VERP and VFT
      and prolonged QTc. The intravenous infusion of magnesium sulphate solution
      depressed further VFT and plasma potassium and increased VERP. The acute infusion
      of potassium chloride solution increased plasma potassium and VFT. In group II B,
      plasma electrolyte levels and electrophysiological variables were not affected.
      We conclude that the clinically demonstrable, antiarrhythmic effect of magnesium
      infusion can be attributed to prolonged VERP. Magnesium sulphate infusion,
      however, produced potassium depletion and decreased VFT (a pro-arrhythmic
      effect). These adverse effects can be avoided infusing magnesium chloride
      solutions.

PMID- 9035479
TI  - Growth acceleration in children with chronic renal failure treated with growth
      hormone-releasing hormone (GHRH).
AB  - Growth retardation is a prominent clinical manifestation in children with chronic
      renal failure (CRF). Nine children with CRF (3 on conservative treatment; 3 on
      dialysis and 3 after renal transplantation) aged 1.6 to 14.0 (x +/- SE: 8.1 +/-
      1.4) years, were treated with twice daily subcutaneous injections of 26 +/- 2.4
      micrograms/kg/day growth-hormone-releasing-hormone [GHRH (1-29) NH2 Serono
      (Geref)] during 3 to 6 months. Mean serum urea and creatinine remained stable,
      although 2 patients on conservative treatment showed a moderate increase in serum
      creatinine. At the start of the study, height SDS was -2.2 +/- 0.2 (x +/- SE),
      growth velocity was 4.5 +/- 1.0 cm/year (-2.3 +/- 0.6 DS for chronological age)
      and growth hormone (GH) response to acute GHRH test (1 microgram/kg IV) was 62 +/
      17.5 ng/ml. Five patients increased height velocity from 3.8 +/- 0.7 to 8.0 +/-
      1.2 cm/year (paired t test, p < 0.05). The peak GH response to GHRH was
      significantly higher in the group of growth non-responders than in the responders
      (p < 0.05). In conclusion, 5 out of 9 short children with CRF, 3 on conservative
      treatment, 1 on dialysis and 1 post renal transplantation, showed improved growth
      in response to GHRH therapy. No consistent effect on renal function was detected.
      GHRH may be an alternative therapy to increase growth velocity in patients with
      CRF.

PMID- 9035480
TI  - Hormone replacement therapy increases trabecular and cortical bone density in
      osteoporotic women.
AB  - Twenty five postmenopausal Caucasian women with established osteoporosis or
      severe osteopenia were treated with continuous combined estrogen/progesterone (2
      mg 17 beta estradiol and 5 mg medroxiprogesterone) and 1000 mg of calcium daily.
      The mean age of the patients was 57 +/- 6 years (range 44 to 69 years), and the
      average postmenopausal interval was of 10.7 +/- 4.2 years. The bone mineral
      density (BMD) of the lumbar spine and proximal femur was determined using DXA
      densitometer at baseline, 12 and 24 months of treatment. Serum and urine
      measurements were done at baseline and 12 months. After 24 months of treatment
      bone mineral density increased at the trochanter 10.2% p < 0.001, lumbar spine
      9.6% p < 0.001, Ward's triangle 8.6% p < 0.005 and femoral neck 5.7% p < 0.001 in
      comparison to basal levels. In the first year of treatment serum alkaline
      phosphatase and urinary hydroxiproline diminished significantly in comparison to
      basal levels (p < 0.001, for both). In conclusion, this study indicates that
      continuous combined estrogen progesterone therapy decreases bone turnover and
      increases BMD of the spine, femoral neck and trochanter in established
      osteoporosis.

PMID- 9035481
TI  - [Immunohistochemical detection of bcl-2 and MIB-1/Ki-67 in breast cancer:
      retrospective analysis of 238 cases].
AB  - We considered of interest to determine the possible interrelationship between the
      proliferation-related marker MIB-1/Ki-67 and the bcl-2, a protein involved in the
      blockage of apoptosis, and whether they contributed to the prognosis of breast
      cancer. For this purpose we carried out a retrospective immunohistochemical study
      of 238 cases of stage I and II breast carcinomas with a follow up of at least 5
      years. The study revealed that high expression of MIB-1 was associated with high
      nuclear and histological grades (p < 0.001 for both), negative estrogen receptor
      status (p = 0.009) and progesterone status (p = 0.004), and younger age (p =
      0.014). High bcl-2 expression was associated with smaller tumor size (p = 0.001),
      positive estrogen and progesterone receptors (p < 0.001 for both); low nuclear
      grade (p < 0.001), low histological grade (p < 0.002), stage I disease (p = 0.01)
      and low MIB-1 expression (p = 0.025). The univariate Cox regression showed a
      significant association of high MIB-1 expression (p = 0.002) and low bcl-2
      expression (p = 0.04) with shorter OS. Furthermore, MIB-1 expression was a
      significant independent predictor of OS (p = 0.002) as showed by stepwise Cox
      regression analysis.

PMID- 9035483
TI  - [Identification of a tumor antigen associated to the estrogen receptor in
      axillary lymph nodes of breast cancer patients].
AB  - Sixteen axillary lymph nodes were incubated with sera from patients with mammary
      carcinoma. Using immunofluorescence staining sera recognized antigenic
      determinants on follicular dendritic cells (FDC) within the follicle centers.
      These results were confirmed with isolated and cultured FDC that were incubated
      with the same sera. All the results were negative with normal sera. We also found
      a cell population positively reacting with a monoclonal antibody against an
      estrogen receptor associated protein (ERAP) in subcapsular and cortical sinusae
      and germinal centers. Phenotype identification of ERAP+ cells indicated that they
      presented characteristics of macrophages and FDC respectively. Lymph nodes from
      other malignancies were negative for ERAP. These findings suggest that the
      tumoral antigen could be either the protein associated with the estrogen receptor
      or the receptor itself. The ERAP could be transported by the macrophages from the
      tumor to the regional lymph nodes where it could be processed and maintained
      during a long time by FDC, since it is known that these are the most efficient
      antigen presenting cells.

PMID- 9035482
TI  - [Study of cases of leishmaniasis in the Province of Salta: evidences of mixed
      infection with Trypanosoma cruzi and Leishmania spp].
AB  - In many regions of South America there are overlapping endemic areas for American
      Trypanosomiasis (Chagas' disease) and Leishmaniasis. T. cruzi and Leishmania spp,
      the causative agents of these parasitoses belong to the Trypanosomatidae family
      and share various antigens that cause cross-reactivity in serological diagnosis
      when complex antigenic mixtures are used. We studied patients who sought medical
      attention because of cutaneous or mucocutaneous lesions typical of leishmaniasis
      infection. These patients were from the province of Salta where Trypanosomiasis
      and Leishmaniasis are endemic diseases. Sixty-two patients gave a positive
      Montenegro skin test and, of these, 53 (85, 48%) showed the presence of
      amastigotes in Giemsa stained smears of dermal scrapings. Seven patients were not
      included because they were negative for both assays. We analyzed the
      leishmaniasic sera against homologous antigens to study the immune response and
      against complex heterologous antigens from T. cruzi to evaluate cross-reactivity
      phenomena. We also tested these sera against specific antigens for diagnosis of
      Chagas' disease in order to search for mixed infections. When complex antigens
      from leishmania were used, the sera showed an unusually strong antibody response
      100% positive by IFA, 88.7% by ELISA and 80.6% by immunoblotting. Furthermore,
      significant cross-reactivity was found when conventional antigens for the
      serodiagnosis of Chagas' disease were used: 74.19% by IHA, 91.93% by IFA, and
      76.80% by ELISA. We have previously purified by immunoaffinity, using a
      monoclonal antibody, an antigen termed Ag163B6 which is not present in L.
      mexicana. This antigen has shown the ability to specifically differentiate sera
      of chronic chagasic patients from those of leishmaniasic patients in ELISA.
      Furthermore, recent studies from our laboratory by immunoblotting, have
      demonstrated that chronic chagasic patients exhibit a specific reactivity pattern
      against T. cruzi epimastigotes that can be distinguished from those presented by
      leishmaniasic patients in spite of cross-reactive antigens. According to the
      results obtained in these assays, we classified the patients in two groups: 1)
      Patients with evidence of T. cruzi infection, those who tested positive in at
      least one assay: 2) Patients with no evidence of T. cruzi infection who were
      negative for both assays. More than 50% (32/62) of the patients showed strong
      evidence of mixed infection with T. cruzi. On the other hand, high cross
      reactivity between these two parasitoses was shown in the second group without
      any evidence of T. cruzi infection since 18 out of 30 were positive in at least
      two conventional serological reactions. This implies that they would be
      misdiagnosed as chagasics if conventional reactions were used. These results
      emphasize the importance of the use of defined antigens and appropriate
      techniques for the differential diagnosis of these parasitoses, which is more
      important in areas endemic for both of them.

PMID- 9035484
TI  - Influence of L-triiodothyronine on rat somatotroph cells.
AB  - The L-Triiodothyronine (L-T3) has a direct influence on the population of
      somatotrophs in rat pituitary gland. This effect is dose-dependent and induces
      both proliferation of somatotrophs and striking changes in the synthesis and
      secretion of growth hormone (GH). Daily injections of 5 micrograms L-T3 for 7
      days increased significantly the synthesis and storage of GH in pituitary gland,
      but the GH release was partially blocked. By contrast, injections of 10
      micrograms L-T3 promote rapid synthesis and secretion of GH with removal of the
      cytoplasmic stores of the hormone and a consequent rise of serum levels. A close
      correlation was found between levels of stimulation and proliferation or
      retrogression of lactotroph cell population.

PMID- 9035485
TI  - [Autoimmune hypoglycemia syndrome with specific anti-human insulin antibodies].
AB  - A 33 year old woman with episodes of severe hypoglycemia is presented. The
      studies showed anti-insulin antibodies and variable C-peptide levels. Circulating
      insulin measured after acid-ethanol extraction, was of 1,600 uU/ml and shown to
      be human insulin after characterization by HLPC. Specific anti-human insulin
      antibodies were of high affinity (Ka1: 6.20 x 10(10) M-1; Ka2: 2.42 x 10(9) M-1).
      A small cross-reactive porcine and bovine antibody subpopulation was also
      detected (IgG, light k type chain). Plasmapheresis was undertaken when symptoms
      were spontaneously declining and turned antibody title negative. Prolonged follow
      up showed no relapse of this syndrome.

PMID- 9035487
TI  - [Undifferentiated gastric carcinoma of lymphoepithelioma type with Epstein-Barr
      virus].
AB  - We are presenting the case of a 62-year-old man with a gastric tumor which turned
      out to be an undifferentiated carcinoma lymphoepithelioma type. The epithelial
      nature of the cells was confirmed by immunohistochemistry. The presence of
      Epstein-Barr virus, limited to the epithelial cells, was demonstrated by in situ
      hybridization. These findings confirm data from the literature and support the
      possible etiopathogenic relationship between Epstein-Barr virus and
      undifferentiated carcinoma lymphoepithelioma type of the stomach. We are unaware
      of any other report of this type of neoplasm in our country.

PMID- 9035486
TI  - [Native-valve endocarditis produced by Lactobacillus casei sub. rhamnosus
      refractory to antimicrobial therapy].
AB  - Lactobacillus endocarditis is a rare infection. In fact, only 42 cases have been
      described in the literature from 1938 up to date. In only 17 previously reported
      cases have patients been cured with medical therapy alone. Although infections
      produced by Lactobacillus spp, have been described in our country, none of them
      included endocarditis. We report herein a case of endocarditis due to a
      vancomycin-resistant strain of Lactobacillus casei sub. rhamnosus in a 29-year
      old man with prolapse of the mitral valve. He required surgical replacement of
      his valve because of the poor response to antimicrobial therapy with penicillin
      and gentamicin. The patient displayed a successful clinical outcome, with no
      evidence of recurrence along the subsequent 2 years. We point out the need to
      accurately identify Lactobacillus spp. in isolates from blood cultures of
      patients with endocarditis, since these bacteria may often be mistaken for other
      species more frequently associated to this infection, which usually respond to
      conventional antimicrobial therapy. Furthermore, we suggest that early surgical
      replacement should be considered when lactobacillus endocarditis is diagnosed.

PMID- 9035488
TI  - [Heart insufficiency, ventricular fibrillation and hepatic insufficiency in an
      old woman].

PMID- 9035489
TI  - [Prophylaxis of venous thrombosis, yes but...].
AB  - Prevention of venous thromboembolism (VTE) can be achieved through mechanic or
      pharmacological means. For the latter, unfractionated low dose heparin, low
      molecular weight heparins and oral anticoagulants are successfully and widely
      employed. Results of controlled and uncontrolled studies favour the use of
      prophylactic heparin in different clinical and surgical conditions such as
      myocardial infarction, stroke, orthopedic or prolonged surgery and surgical
      interventions in patients older than forty. Useful parameters to evaluate the
      results of VTE prophylaxis are discussed as well as timing, duration,
      effectiveness, side effects and costs of therapy. Although the benefits of VTE
      prophylaxis in high risk patients are clear, it is not routinely employed in
      Argentina.

PMID- 9035491
TI  - [Nephrology and gene therapy: basic science for the clinician].

PMID- 9035490
TI  - [Physiopathology of preeclampsia].
AB  - Preeclampsia is a disease which appears only during pregnancy. It is highly
      widespread, and in the underdeveloped countries is the leading cause of maternal
      mortality. Nowadays it is considered a disease originated in the activation of
      the vascular endothelium triggered by placental ischemia. The latter is produced
      by a defect in the trophoblastic invasion of the spiral arteries of the uterus.
      Genetic, immunologic and biochemical causes have been postulated in the attempt
      to explain this defect in the trophoblastic implant, but whatever the cause, the
      endothelial activation produces several chemical mediators affecting the function
      of all organs, and then generating preeclampsia related syndromes. The prevention
      of this disease occupies a special place in research and there are numerous
      trials with aspirin and calcium being developed at the moment.

PMID- 9035492
TI  - [Memory loss in dementia, old drama and new hypothesis].

PMID- 9035493
TI  - [Hyperinfection by Strongyloides stercoralis as first manifestation of AIDS].

PMID- 9035494
TI  - [The use of biological indices on environmental quality assessment].
AB  - The aquatic ecosystems quality can be evaluated through the analysis of physico
      chemical and biological parameters. However, the biological parameters differ
      from the physico-chemical ones, having the advantage of providing information on
      the water quality concerning longer periods of time--specially if one considers
      sessil organisms--thus reflecting, in a better way, the general ecological
      conditions of the water body. It is necessary, though, that the taxonomic
      information be translated into simple numerical values (indices), in order to
      simplify its interpretation as well as providing subsidies for the elaboration of
      water quality criteria. Several numerical biological indices can be applied, some
      of them to specific communities, and others to the hole biological community of
      an aquatic environment. Three kinds of indices are more generally applied to
      evaluate the pollutant impacts on aquatic communities: biotic, diversity and
      community comparison indices. The biotic indices will measure the variation in
      terms of tolerance and relative sensitivity of the occurring organisms to a
      certain pollution condition; the diversity indices evaluate the effect of
      pollution in terms of the community structure; the community comparison indices
      (also named similarity or dissimilarity indices) establish the effects of
      pollutants on the community composition. It is important, for the numerical
      indices users, to know the limitations of each method, so that the interpretation
      of the values obtained may be made in the light of such limitations.

PMID- 9035495
TI  - [Capillaroscopy in patients with chronic alcoholic pancreatitis].
AB  - The aim of this study was verify frequency and morphological presentations of
      microangiopathy in patients with alcoholic chronic pancreatitis, using nailfold
      capillaroscopy. All patients showed morphological and functional capillary
      abnormalities. None of them had a normal capillaroscopy. Our findings may suggest
      an important role of microcirculation in Alcoholic Chronic Pancreatitis
      pathogenesis and/or its course.

PMID- 9035496
TI  - [Relationship between breast cancer, breast sensitivity, breast feeding and brain
      laterality].
AB  - The relationship between sensitivity, breast nursing, brain laterality and risk
      of breast cancer is controverse in the literature. In order to clarify whether
      these parameters are related to the presence of breast cancer, we assessed 100
      following women with this neoplasm. Most of women were white (61%), followed by
      black (30%) and coloured (9%). Previous pregnancies were related by 75% of
      patients, but 62 women had abortions. Breast nursing was affered by 66 of them,
      that preferred to nurse by the left breast (25), right breast (13) or
      indifferently (28). This preference is related to comfort. A relation between
      side of the cancer and breast sensitivity seems to occur. In conclusion, multiple
      pregnancies, long period-nursing or brain laterality did not protect women
      against breast cancer.

PMID- 9035497
TI  - [Distal pancreatectomy with conservation of the spleen].
AB  - Conventional resection of the body and tail of the pancreas usually involves
      splenectomy. There are evidence that spleen removal can lead to septic and
      hematological complications and should, therefore, be avoided when possible.
      Distal pancreatectomy with spleen conservation has been described by specialized
      centers with good results. This report describes our experience in 8 cases with
      conservation of the spleen during the resection of the body and tail of the
      pancreas. The technique has been applied in patients with pancreatic
      neuroendocrine tumors (n = 4), cystic tumors (n = 3) and cystic-papillary tumor
      (n = 1) with no complications and good late results in all cases.

PMID- 9035498
TI  - [Results of conventional cholecystectomy. Experience in a university hospital].
AB  - The experience with open cholecystectomy in an university affiliated hospital is
      documented in this report. We studied retrospectively 221 patients operated
      between 1987 and 1992, type of surgery, morbidity and mortality were analyzed.
      There were 171 (77.3%) cholecystectomy alone and 50 (22.7%) cholecystectomy with
      other biliary surgery (BS). Pulmonary, urinary and wound complications were the
      most common. Overall incidence of complications was 7.2%. For patients with
      cholecystectomy alone morbidity was 3.5% and for patients with BS morbidity was
      20% (p < 0.002). There were no mortality in this group of patients.

PMID- 9035499
TI  - [Osteomyelitis by Salmonella enteritidis and sickle cell hemoglobinopathy. Report
      of a case and review of the literature].
AB  - Salmonella osteomyelitis is an uncommon disease, usually associated with sickle
      cell anemia and other hemoglobinopathies, as well as with other disease states.
      In this case, osteomyelites was apparently caused by hematogenous spread of an
      enteric infection by Salmonella enteritidis. Bone involvement, in vertebral
      bodies, was resolved after prolonged clinical treatment with antibiotics. We
      discuss the pathogeny and compare the findings of four case with others related
      in literature.

PMID- 9035500
TI  - [Mixoma of maxilla in a child, report of case and review of the literature].
AB  - A case of maxillar mixoma in a child aged one year and three months is reported.
      The child was submitted to a partial ressection of the maxilla and a
      reconstruction of the orbital floor with a Kirchner wire and a polipropilene Wire
      netting. The picture taken one year and eight months later shows the favorable
      result of the operation.

PMID- 9035501
TI  - [Pharyngoesophageal dysfunction: report of case and review of literature].
AB  - Buccopharyngeal motor disorders causing difficulties in swallowing are frequently
      encountered in clinical medicine. Affected patients manifest distinctive clinical
      features and pose special problems in their management. A case report is
      described and summarize the pathogenesis, consequences, evaluation, treatment and
      some selected clinical conditions that are associated with buccopharyngeal
      dysphagia.

PMID- 9035502
TI  - [Learning theories and medical education].
AB  - The author analyses the most important aspects of learning theories: the
      behaviorist, the gestaltic and the construtivist ones and concludes that the most
      effective attitude assimilates all positive constributions of each theory.
      Examining three basic learning principles, the author also presents their
      relation to medical educative components: knowledge retainment, psycho-motor
      habilities breeding and interpersonal attitudes development.

PMID- 9035504
TI  - [Lyme disease in Chile. Prevalence study in selected groups].
AB  - BACKGROUND: The prevalence of Lyme disease in Chile is unknown. AIM: To study the
      existence and epidemiology of Lyme disease in Chile. PATIENTS AND METHODS: One
      hundred eighteen patients with signs or symptoms suggestive of Lyme disease were
      studied. Antibodies against Borrelia burgdorferi were measured using ELISA and
      indirect immunofluorescence screening tests. Positive cases were confirmed with
      ELISA using a purified antigen and Western Blot analysis. Human biological
      samples and ticks were cultured in BSK-H medium. RESULTS: Five patients, three
      with dermatological manifestations and two with facial palsy and other
      neurological symptoms, had antibodies against Borrelia, measured by ELISA and
      indirect immunofluorescence. However the presence of IgM antibodies by ELISA
      using purified antigen, was confirmed in only one case. All sera and
      cerebrospinal fluids were negative on Western Blot Analysis. No plasma, skin, CSF
      or thick culture yielded Borrelia CONCLUSIONS: We could not confirm the existence
      of Lyme disease in Chile. Positive screening with negative confirmatory test
      suggests false positive non-specific reactivity or that local Borrelia are
      antigenically different compared to North American strains.

PMID- 9035503
TI  - [Natural history of human immunodeficiency virus infection in a cohort of Chilean
      patients].
AB  - We characterized clinical manifestations and the risk to develop AIDS in a cohort
      of 32 patients infected with human immunodeficiency virus without AIDS A
      multivariate analysis was performed to determine association between the
      progression of infection and control variables (socioeconomic level, age, sex and
      sexual preferences) and causal variables (psycho-social changes, significant
      clinical events, stress scoring and sexual activity). The cumulative AIDS
      incidence, defined as a CD4 lymphocyte count below 200 cells/cm3 was 50% at 6.5
      years and 82% at 8 years. Using clinical criteria to define AIDS, 50% developed
      the disease at 8 years of follow up. Among studied factors, only age (faster
      progression at higher age) and time of evolution were associated with progression
      in stages before AIDS, the most frequent diseases were acute diarrhea, sexual
      transmission diseases, oral candidiasis, sinusitis and varicella zoster
      infections. The reduction; of CD4 lymphocytes-below 200 cells/cm3 always preceded
      the symptoms of the disease. Two patients have remained more than eight years
      without clinical or immunological deterioration.

PMID- 9035505
TI  - [Frequency and histopathologic features of chronic gastritis in 300 patients
      without endoscopic lesions].
AB  - Three gastric mucosal biopsies were obtained from 300 patients showing a normal
      upper digestive tract endoscopy. Histologically, in 9% of the patients the
      biopsies were normal: in 87%, showed a common-type chronic gastritis, and in 4%
      showed a reactive (chemical or reflux-type) gastritis. Helicobacter pylori was
      present in 25.9% of the patients without gastritis, in 33.3% of the patients with
      reactive gastritis, and in 87.7% of those with common-type gastritis. In 19.9% of
      the patients with common-type chronic gastritis there was intestinal metaplasia,
      consisting of type I metaplasia in 14.1%, type II in 3.1% and type III metaplasia
      in 2.3%. The association of type III intestinal metaplasia with the other forms
      of metaplasia, its lower frequency and its tendency to be present in older
      patients supports the hypothesis that type III incomplete colonic metaplasia
      represents a more advanced stage than complete and incomplete small bowed
      metaplasia of the gastric mucosa.

PMID- 9035506
TI  - [Epidermoid carcinoma of the cervix uteri: molecular abnormalities of p53 and rb
      genes].
AB  - The inactivation of p53 and rb genes has been implicated in the pathogenesis of
      cervix uteri carcinoma. Although this neoplasia presents high incidence and
      mortality rates in Chile, there are not studies about its molecular
      abnormalities. We investigated the frequency of loss of heterozygocity (LOH) at
      p53 and rb genes in 17 invasive squamous cell carcinomas of the cervix uteri,
      using microdissection technique from microslides and microsatellite sequences
      amplification by PCR. Moreover, we investigated the immunohistochemical
      expression of p53 protein in 30 invasive squamous cell carcinomas LOH was
      detected in 6/12 of informative cases (50%) at p53 gene and in 3/10 (30%) at rb
      gene. The p53 protein immunohistochemical expression was 47% (14/30 cases). LOH
      at p53 gene in cases without p53 protein immunohistochemical expression was
      observed. We concluded that p53 gene molecular abnormalities are important in the
      pathogenesis of squamous cell carcinoma of the cervix uteri, in contrast than LOH
      at rb gene.

PMID- 9035507
TI  - [Incidence of insulin-dependent diabetes mellitus in Santiago, Chile (1990
      1993)].
AB  - The aim of this study was to determine IDDM incidence in the Metropolitan Region
      of Chile, during the period 1990-1993 as part of the Multinational Project for
      Childhood Diabetes (WHO DIAMOND Project Group). The studied population was
      1499.784 inhabitants. All children in whom the diagnosis was made between January
      1, 1990 and December 31, 1993 were included. We used a retrospective and
      prospective search and confirmation method, using as data sources public and
      private hospitals and medical records of Pediatricians. The Juvenile Diabetes
      Foundation was used as a secondary data source. All cases had at least two
      confirmation sources. A total of 176 new cases (90 male) were diagnosed in the
      study period, with an annual incidence of 2.92/100,000 for females and 2.95 for
      males. The group of children from 10 to 14 years old had the highest incidence
      rate (4.9/100,000), specially in women (5.25/100,000). The yearly incidence was
      1.31 in 1990, 2.71 in 1991, 2.93 in 1992 and 3.7/1000,000 in 1993. It is
      concluded that the Metropolitan Region has one of the lowest incidences of IDDM
      in Latin America, although it increased along the study years.

PMID- 9035508
TI  - [Initial therapy of primary nephrotic syndrome in children: evaluation in a
      period of 18 months of two prednisone treatment schedules. Chilean Co-operative
      Group of Study of Nephrotic Syndrome in Children].
AB  - Ninety six patients aged from 6 months to 15 years and were admitted to Chilean
      hospitals with the diagnosis of primary nephrotic syndrome in a period of 30
      months. These patients were randomly separated in two groups, group A received
      prednisone for 8 weeks and group B received the same drug during 12 weeks. All
      patients were evaluated at 6, 12 and 18 months after the end of treatment. The
      moment and number of relapses per patient, accumulated percentage of relapses,
      relapse rate per 100 patients, total number of relapses and complications were
      assessed. Frequent relapsers were subjected to a kidney biopsy, leaving in the
      protocol only those patients that had minimal changes. Patients resistant or
      dependent to steroid therapy were discarded. Thus we report the results of 56
      treated patients followed during 18 months. No differences in analyzed parameters
      were observed between the two treatment groups. It is concluded that these
      preliminary results do not support the prolongation of prednisone treatment in
      children with primary nephrotic syndrome.

PMID- 9035509
TI  - [Neodymium YAG laser in treating prostatic adenoma].
AB  - BACKGROUND: Conventional surgery and transurethral ablation are the treatments of
      choice for benign prostatic hyperplasia. AIM: To report our experience with
      Neodynium: YAG laser ablation of prostatic adenomas. PATIENTS AND METHODS:
      Revision of 182 patients subjected to Laser ablation of benign prostatic adenoma
      of whom 28 had a complete urinary retention and 50 were considered of high
      surgical risk. RESULTS: One hundred eighty patients had spontaneous voiding after
      surgery, there were no intraoperatory complications and were discharged 6 to 24
      hours after the procedure. Urinary flow increased from 8 ml/sec in the
      preoperative period to 20 and 21 ml/sec, two and six months after surgery.
      Symptom score decreased from 12 to 1.2 points. Seven patients had late hematuria
      and two required vesical lavage and cystoscopic clot drainage. Ten patients had a
      positive urine culture. 12 had lack of ejaculation and 75%, had some degree of
      dysuria. CONCLUSIONS: Neodynium YAG laser ablation of benign prostatic adenoma
      seems to be efficient and safe.

PMID- 9035510
TI  - [Renal transplantation in patients with neurogenic bladder].
AB  - BACKGROUND: Renal transplantation can be done in patients with neurogenic bladder
      and clean intermittent self catheterization maintains renal function AIM: To
      retrospective assess the results of renal transplantation in patients with
      neurogenic bladder. PATIENTS AND METHODS: The medical records of seven patients
      aged 10 to 22 years old (3 female) followed during 7 to 32 months were reviewed.
      All patients had urinary tract infection, prior to transplantation, were
      instructed on self catheterization and received tri-associated immunosuppression.
      RESULTS: Grafts came from alive related donors in 5 patients and from cadavers in
      two. Prior to transplantation, three patients were subjected to nephrectomy and
      three to bladder enlargement, leaving a pigtail catheter. After transplantation,
      one lymphocele was drained, one uretherostomy due to an impacted lithiasis and
      one nephrectomy plus vesical enlargement due to intravesical pressures over 40 cm
      H2O, were done. One uretheral stricture was treated with dilatation. Seven
      episodes of pyelonephritis, 19 urinary tract infections and 77 asymptomatic
      bacteriurias were documented. Serum creatinine at the end of follow up ranged
      from 0.7 to 2.1 mg/dl. There were 0.7 acute rejection episodes per patient and
      all grafts survived. CONCLUSIONS: Renal transplantation in patients with
      neurogenic bladder is feasible, performing a vesical enlargement. There is
      however a high frequency of infectious episodes.

PMID- 9035511
TI  - [Effect of the Nucleus CMP forte in 46 patients with progressive spastic
      paraparesis. Randomized and blind study].
AB  - BACKGROUND: Idiopatic or HTLV-1 associated progressive spastic paraparesis does
      not have a clear etiology or treatment. AIM: To assess the effects of a
      medication containing cytidinmonophosphate, uridintriphosphate and vitamin B 12
      in the treatment of progressive spastic. PATIENTS AND METHODS: Patients with the
      disease were randomly assigned to receive the Nucleus CMP forte (containing
      dysodic cytidinmonophosphate 5 mg, trisodic uridintriphosphate 3 mg and
      hydroxicobalamin 2 Mg) tid or placebo during six months. Gait, spasticity, degree
      of neurogenic bladder and somatosensitive evoked potentials were assessed during
      treatment. RESULTS: Forty six patients aged 25 to 79 years old were studied, 24
      were female and 29 HTLV-1 positive. Twenty two were treated with the drug and the
      rest with placebo. Gait and spasticity improved in 7 of 22 patients receiving the
      drug and 1 of 24 receiving placebo (p < 0.05). Neurogenic bladder improved in 10
      of 22 receiving the drug and 4 of 24 receiving placebo (NS) Somatosensitive
      evoked potentials improved in four of seven patients treated with the drug and in
      two of seven treated with placebo. CONCLUSIONS: The medication caused a modest
      improvement in patients with progressive spastic paraparesis and was free of side
      effects.

PMID- 9035512
TI  - [Toxic megacolon secondary to ischemic colitis. Report of a case].
AB  - We report a 67 years old male that consulted due to bloody diarrhea of several
      months of evolution and emaciation. According to endoscopic and radiological
      findings, the diagnosis of severe ulcerative colitis was made. Fifteen days after
      admission, the patient was subjected to an emergency total colectomy due to a
      toxic megacolon. The pathological study showed an ischemic colitis with extensive
      longitudinal ulcers in the antimesenteric border, presence of granulation tissue
      with inflammation and transmural fibrosis. Intestinal transit was reconstituted
      six months later and after 12 months of follow up the patient is in good
      conditions.

PMID- 9035513
TI  - [White piedra. Report of a case].
AB  - The most common superficial mycosis caused by Trichosporon beigelii is white
      piedra. We report a 18 years old male that had in several hairs of the scalp,
      white-yellowish nodules of 1 mm diameter, agglutinated or forming chains, even
      forming threads, with a greasy aspect. Trichosporon beigelii was identified in
      cultures. Oral and topical antimycotics were prescribed and the patient was lost
      from follow up.

PMID- 9035514
TI  - [Treatment of multiple sclerosis with interferons].
AB  - Despite the important achievements in clinical and experimental aspects of
      demylinating diseases and multiple sclerosis (MS), its pathogenesis still remains
      unknown. The most commonly held view is that it is an autoimmune disease, related
      in some way to a viral infection, that occurs in genetically susceptible basis.
      Based on this, many current treatments for MS are designed to modulate the immune
      response and interferons are an example. Only beta interferon (out of delta and
      gamma interferon) has a dose dependent efficacy in phase III clinical trials, as
      treatment for remitting-relapsing forms. It produces a reduction in exacerbation
      rates and in the burden of the disease, measured by Magnetic Resonance imaging.
      The clinical use of beta interferon considering the cost and large treatment
      period, must be cautious, reserving it only for confirmed remitting-relapsing
      modalities of MS. There is no clear cut evidence that beta interferon is useful
      for chronic-progressive MS.

PMID- 9035515
TI  - [Pragmatism versus metaphysics: a controversy about brain death].
AB  - The concept of brain death is still controversial. The Chilean case, as a result
      of a future transplantation law, seem to demonstrate this issue. The aim of this
      work is to contribute to the debate. A recent international polemic between
      metaphysic and pragmatic authors is approached, to establish bases to reject or
      accept the issue, after giving a brief history of the concept, from its medical
      origin to its transcendence to other areas as the law. The metaphysical rejection
      and the socio-cultural frame of the medical attitude that accepts brain death,
      are commented. It is concluded that the best defense of metaphysical point of
      view is the right to exclusion of minorities. Finally, brain death is criticized
      from a socio-cultural point of view of medical acts as a post-metaphysical
      concept of "useful death" and because of its relationship with "health
      production".

PMID- 9035516
TI  - [Other factors in gallbladder cancer].

PMID- 9035518
TI  - [Diagnostic certainty: is it the final aim of the internist?].

PMID- 9035517
TI  - [Prevalence of antibody to hepatitis C virus in blood donors. Analysis of
      confirmed results].

PMID- 9035519
TI  - [Emphysematous pyelonephritis].

PMID- 9035520
TI  - [Region, age and sex of Chilean mortality in 1992].

PMID- 9035521
TI  - [Don Rodolfo Armas Cruz: physician, professor and teacher].
AB  - The present issue of Revista Medica de Chile contains tributes to the late
      Profesor Rodolfo Armas Cruz prepared by the Editors and, by invitation by two of
      his closest disciples and collaborators. With the decease of Professor Dr Rodolfo
      Armas Cruz on November 26, 1995, disappeared a representative of a medical
      generation, whose unique work transformed national medical tasks, lending
      prestige to Chilean medicine. His peers recognized in him as a distinguished
      master and his work was so vast that is difficult to underscore a particular
      aspect. Over and above his books and scientific reports, remains the testimony of
      hundreds of his disciples distributed along Chile that, marked by his teachings
      trying to follow his path. The honors, awards and titles never separated him from
      an austere way of life, dedicated to work besides the ill, his students and his
      beloved Medical Service at the San Juan de Dios Hospital. His transcendental name
      and work, incorporated to the history of Chilean medicine, will be an example for
      actual and future medical generations.

PMID- 9035522
TI  - [Homage to professor Rodolfo Armas Cruz, MD, professor of Chilean Medicine (1905
      1995)].

PMID- 9035523
TI  - [Homage to professor Rodolfo Armas Cruz, MD (1905-1995), a leader of Chilean
      Medicine].

PMID- 9035524
TI  - [Mechanisms of dream-sleep-wakefulness cycle].
AB  - For the occurrence of each state of sleep (slow wave sleep, paradoxical sleep)
      there are two neuronal networks. The first one called executive is responsible
      for the sleep phenomenology; the second called permissive is for the triggering
      of sleep. Wakefulness depends on a very complex system (10 structures) including
      the permissive networks which inhibit sleep. Sleep onset is thought as a blockade
      of the waking state by an antiwake network synthesizing hypnogenic factors. Such
      a regulation allows to suggest that insomnia is a wake trouble depending on a
      revisited therapy.

PMID- 9035525
TI  - [Regulation of sleep].
AB  - Sleep regulation calls for 3 processes: the first one is the homeostatic process
      increasing during wakefulness and decreasing during sleep, the second one is the
      circadian process depending on the circadian oscillator which controls
      temperature and alertness rhythms, and the third one is the ultradian process: it
      determines the NREM/REM periodicity. In the 2 process model of sleep regulation,
      the power density of the delta band (0.75-4.5 Hz) called slow wave activity (SWA)
      and obtained by spectral analysis, is supposed to reflect the variations of a
      homeostatic recovery process (process S) that increases in a saturating
      exponential way during wakefulness. Its decrease is expressed by the exponential
      decline of SWA during sleep. Process S interacts with the circadian process
      (process S) that determines the sleep timing. The 2 process model has been
      further modified to account for the semicircadian sleep propensity, although no
      satisfactory fit has been obtained with laboratory data. No impairment of NREM
      sleep homeostatic sleep regulation can be evidenced in narcoleptic patients who
      seem more sensitive to homeostatic regulation of sleep than normal subjects. On
      the other hand the circadian process appears to be weaker in narcoleptic patients
      than in normal subjects; this permits the occurrence of a strong ultradian
      component explaining diurnal sleep episodes.

PMID- 9035526
TI  - [Insomnia].
AB  - Insomnia is frequently met in everyday medical practice. Half of the population
      can present this symptom during their life-time. Objective impairment of sleep,
      as well as complaints of patients, are various and require investigations. Two
      forms of insomnias, transient and chronic, can be identified. The former is
      mainly factual and the latter is consecutive to a longstanding organic or
      psychiatric condition or constitute what is generally referred to primary chronic
      insomnia. The form, the duration, the severity and the etiology are important
      clues for the choice of treatment, notably the prescription of hypnotics.

PMID- 9035527
TI  - [Treatment of insomnia].
AB  - Insomnia is not frequently a disease and is rather to be considered as a symptom
      or a physiological signal. Consequently, its treatment should tend to be
      etiological. If a pharmacological sleep inducing intervention proves necessary,
      it has to be included within a more general synchronizing approach.
      Resynchronizing techniques lie on chronophysiology i.e. rhythms hygiena, control
      of sleep schedules, sleep restriction. Other non-pharmacological approaches
      include behaviorism, paradoxical injunctions, relaxation, psychotherapies.
      Prescription of hypnotics (benzodiazepine or non-benzodiazepine drugs) is
      sometimes necessary and must be submitted to certain rules including indications,
      contra-indications, length of treatment, specific withdrawal techniques.

PMID- 9035528
TI  - [Narcolepsy].
AB  - Narcolepsy is a rather unknown but not exceptional condition. Its prevalence, 2
      to 6/10000, is ranging among this of multiple sclerosis. Narcolepsy is remarkable
      for clinical, polygraphic and immunogenetic features which make it a kind of
      model of disorders of alertness. It was first described in 1877. It has recently
      benefited from consistent pathophysiological progresses, which have been
      facilitated by the discovery of a natural canine model. The two main symptoms are
      irresistible and refreshing episodes of sleep and cataplexy a loss of muscle tone
      emotionally triggered. Polygraphically the sleep onset REM period is the major
      feature. Immunogenetically the condition is remarkable for an almost 100%
      association with HLA DR2-DQ1. Narcolepsy is a debilitating, chronic condition.
      Its treatment is threefold including stimulants against excessive daytime
      sleepiness and irresistible episodes of sleep, modafinil a new compound with
      awakening properties has just been introduced, antidepressants against cataplexy
      and associated symptoms and hypnotics against disrupted sleep.

PMID- 9035529
TI  - [Sleep-related respiratory disorders].
AB  - Sleep-related respiratory disorders are mainly represented by the consequences of
      partial or total upper airway obstruction during sleep, which lead to clinical
      pictures ranging from "pure" snoring to full-blown obstructive sleep apnea
      syndrome, including obstructive sleep hypopnea syndrome and upper airway
      resistance syndrome. These pictures share symptoms like snoring and excessive
      daytime sleepiness. Beyond the social and professional impairment and the
      increased risk of traffic and work accidents, these patients are exposed to the
      complications of systemic hypertension, which is often associated, and of less
      frequent cardiorespiratory failure. The diagnosis is based upon polysomnography
      which demonstrates the ventilation abnormalities. Since stable weight loss is
      most often impossible to obtain, the treatment of choice is based on nasal
      continuous positive airway pressure during sleep. In some selected cases, facial
      bone surgery may be helpful.

PMID- 9035530
TI  - [Sleep-wakefulness rhythm disorders].
AB  - The circadian system is synchronized on 24-hour by the light-dark synchronizer
      and by the social time cue. The circadian rhythm sleep disorders share a common
      underlying chronobiological basis. These disorders may be due to either jet-lag,
      shift-work or to lesions of the peripheral visual pathway. The delayed sleep
      phase syndrome, the advanced sleep phase syndrome, the non 24-hour syndrome as
      well as the irregular sleep-wake patterns are described. Therapeutic approaches,
      in particular with melatonin and (or) bright light, are presented.

PMID- 9035532
TI  - [Diplopia. Diagnostic orientation].

PMID- 9035531
TI  - [Parasomnias].
AB  - Parasomnias are classified as dysfunctions associated with sleep, sleep stages,
      or partial arousals from sleep. The main part of this article is devoted to the
      parasomnias which occur in slow wave sleep and correspond to a partial arousal
      during this state, that is: night terrors, confusional arousals and somnambulism.
      The diagnosis of parasomnias is done on a very precise description of the
      behavior and on its time of occurrence during the night, the notion of a familial
      history of parasomnias is also important. Management depends on the age, the
      frequency of the episodes and the presence or not of a family disruption. Most
      parasomnias are precipitated by stress, and in the younger subjects by an
      interaction between ontogenetic characteristics of sleep and immaturity. In the
      older patients psychological or organic factors must be eliminated.

PMID- 9035533
TI  - [Ulcer of the leg. Etiology, physiopathology, diagnosis, course, treatment].

PMID- 9035534
TI  - [Angina pectoris. Epidemiology, etiology, physiopathology, diagnosis, course,
      treatment].

PMID- 9035535
TI  - [Polyarteritis nodosa. Diagnosis, course].

PMID- 9035536
TI  - [Pleural effusion. Diagnostic orientation].

PMID- 9035537
TI  - [Bronchoalveolitis in infants. Diagnosis, treatment].

PMID- 9035538
TI  - [Imaging].
AB  - The panoply of imaging techniques useful in podology is essentially limited to X
      rays. Standard "standing" and "lying" X-rays furnish most of the required
      information. Arthrography is sometimes performed, in particular for trauma or
      tumour of the ankle. CT scan and MRI make a decisive contribution in difficult
      cases, notably in fractures and in small fractures without displacement. The two
      latter techniques are useful in tendon, ligament and muscular disorders, where
      echography is also informative. Rigorous analysis of radiographies and a good
      knowledge of foot disorders make these imaging techniques efficacious.

PMID- 9035539
TI  - [Hollow foot in adults].
AB  - Contrary to the general impression, the hollow foot is much more common than the
      flat foot. We distinguish three categories of hollow foot: varus hollow (clinical
      form I), valgus hollow (clinical form II), and pseudo-hollow (clinical form III).
      These three clinical forms have a common deviation dynamics, the consequence of
      shortening of the sural-Achilles-calcaneoplantar system. Metatarsalgia often
      precedes deformation of the front of the foot. Talalgia is linked to excess
      traction or to a conflict between the heel and the back of the shoe. Common
      therapy consists of plantar orthoses, eventually toe orthoses and orthopedic
      shoes. When surgery is used in the adult, it is generally not to correct excess
      cavus but to correct problems of the front of the foot such as hallux valgus,
      involvement of the second metatarsal bone (??), or toenails.

PMID- 9035540
TI  - [Flatfoot].
AB  - The flat foot is a very frequent cause of consultation in podology. The lesion is
      rapidly fixed, and osteoarthrosis appears. The diagnosis is clinical. A
      podoscopic and radiographic examination is necessary to appreciate the
      evolutivity of the deformity. The treatment is almost conservative: the wearing
      of orthesis is often sufficient. The indications of the surgery are rare;
      sometimes it is possible to do plastic techniques (in particular on the posterior
      tibial tendon) but, when the foot is painful, the osteoarthrosis is present and
      it is necessary to do arthrodesis, in particular in the talonavicular joint.

PMID- 9035541
TI  - [Static metatarsalgia].
AB  - Static metatarsalgia involves pain of non-inflammatory origin in the region of
      the metatarsal heads. It is caused by a functional disorder or anatomic
      derangement of the architecture over the ball of the foot, whether congenital or
      acquired, evident or not. Clinical examination, including of the shoe and of the
      plantar orthosis, distinguishes five types of anomalies: 1. horizontal
      malalignment of the metatarsal heads with insufficiency at the first metatarsal
      phalangeal joint, dominated by hallux valgus, and involvement of the second
      metatarsal bone, sometimes favouring Freiberg's disease; 2. vertical
      malalignment, with a hollow anterior foot, sometimes complicated by Morton's
      neuroma; 3. a combination of these two anomalies, easily diagnosed but less
      easily treated; 4. possible enlargement of the first metatarsal-phalangeal joint
      (hallux rigidus, sesamoid pathology); 5. no patent architectural anomalies, but
      stress fractures or bone insufficiency fractures of the metatarsals. Only
      clinical examination can orient complementary strategy and examinations.

PMID- 9035542
TI  - [Inflammatory foot disease].
AB  - The pathology of the foot is frequent in the inflammatory rheumatisms. It can
      finally contribute to the diagnosis. In rheumatoid arthritis, the metatarso
      phalangeal joint involvement appears earlier and more obvious. The lesion of the
      midrearfoot is later and the beginning is more indisious, they often evolve in
      pes plano valgus deformity. In spondylarthropathies the involvement of the heel
      and of the toes predominates, but there are more specific symptoms for each
      disease particularly for the psoriasic rheumatism. Local cares, plantar orthoses,
      casts, corticosteroid injections, synoviortheses as well as a good hygiene of
      life are very useful. Surgery helps to keep the functional ability of the patient
      and its indications must be known.

PMID- 9035543
TI  - [Fatigue fractures of the foot].
AB  - A stress fracture is a very localized change in bone remodeling occurring in a
      normal bone that is subjected to an unusual repeated cyclic loading. It is a
      common fracture in military recruits and recreational or competitive athletes. A
      typical medical history and a local bone tenderness at physical examination
      suggest the diagnosis that is confirmed by a local "hot" spot on the radionuclide
      bone scan. Radiographic signs are delayed and inconstant. Radiographs show the
      fracture line or a bone sclerosis as the result of fracture healing. Although
      every bone may be involved, depending on the type of the physical activity,
      metatarsals and calcaneus are the most frequent locations in the foot. The
      treatment of a stress fracture in the foot consists in a 4 to 6 nonweight-bearing
      immobilisation followed by a graduated return to march and sport.

PMID- 9035544
TI  - [Tendinopathies of the foot].
AB  - Tendinitis of the foot is frequent and is generally due to mechanical overload or
      inflammatory rheumatic disorders. It most often involves the posterior tibial
      tendon when obesity and calcaneus valgus combine to contribute to mechanical
      overwork, or in the early stages of rheumatoid arthritis. More rarely, the
      anterior tibial tendon or the fibular tendons are involved. The anatomic-clinical
      stages proceed from oedema to fissuration necrosis and ruptured tendon. The long
      term risk is of a sinking internal arch and a fixed calcaneus valgus. A simple
      but effective treatment is the correction of the calcaneus valgus, but surgical
      arthrodesis may be necessary.

PMID- 9035545
TI  - [Algodystrophy of the foot].
AB  - The foot is one of the most frequent site of the reflex sympathetic dystrophies,
      and clinical data associate pain and vasomotor disturbances. Hyperfixation as
      revealed by bone scan appears early but is nonspecific. X-ray data show
      demineralization that is typically spotty, and sometimes diffuse. Therapeutic
      management associates drug treatment (calcitonin) and rehabilitation based on
      specific rules, in particular, that of "no pain". In the case of failure,
      regional sympathetic blocks are indicated. The etiologies of the reflex
      sympathetic dystrophies vary, but are dominated by trauma.

PMID- 9035546
TI  - [Foot entrapment syndromes].
AB  - Foot's entrapment syndromes are frequent and often ignored cause of pain. Many
      clinical descriptions are presented, but diagnostic and therapeutic proceeding is
      univocal, depending upon to find the conflictual zone (Tinel's sign,
      electrophysiology, infiltrate test) and to pay attention to the different
      etiologic factors (static troubles, traumatism, foot/shoe conflict...).

PMID- 9035547
TI  - [Persistent biological inflammatory syndrome. Diagnostic orientation].

PMID- 9035548
TI  - [Hypercorticism. Physiopathology, etiology, clinical and biological diagnosis].

PMID- 9035549
TI  - [Alzheimer disease. Diagnosis, course].

PMID- 9035550
TI  - [Acute pericarditis. Etiology, diagnosis, course, complications, treatment].

PMID- 9035551
TI  - [Pulmonary tuberculosis and primary-infection tuberculosis. Epidemiology,
      diagnosis, course, treatment, prevention].

PMID- 9035552
TI  - [Edema of the lower limbs. Diagnostic orientation].

PMID- 9035553
TI  - Stability of vinblastine sulphate in 0.9% sodium chloride in polypropylene
      syringes.
AB  - The stability of vinblastine sulphate diluted in 0.9% sodium chloride solution
      for injection was studied. Vinblastine sulphate was reconstituted with 0.9%
      sodium chloride solution for injection to concentration of 1.0 mg/mL and stored
      in polypropylene syringes at 25 degrees C +/- 1 degree C protected from light. On
      different days the solutions were analysed and the vinblastine concentration was
      determined by high-performance liquid chromatography. An high-pressure liquid
      chromatographic method is described for the quantitative determination of
      vinblastine in the presence of its degradation products. The degradation of
      vinblastine was studied by examining the percentage changes from the theoretical
      concentrations for each solution. The results of these studies indicate that
      vinblastine solutions in 0.9% sodium chloride solution for injection (1 mg/mL) in
      polypropylene syringes at 25 degrees C +/- 1 degree C protected from light are
      stable for up to one month.

PMID- 9035554
TI  - Synthesis, local anaesthetic and antiarrhythmic activity of methyl N-(2
      substituted aminopropanoyl)-3-cyanoanthranilates.
AB  - A series of methyl N-(2-substituted aminopropanoyl)-3-cyanoanthranilates (4a-i),
      that are structurally-related to tocainide and lidocaine, was synthesized and was
      found to be active when evaluated for local anaesthetic activity using the frog
      foot withdrawal reflex, the guinea pig wheal derm and the rabbit corneal reflex
      tests. A selected numbers of the series were preliminarily evaluated for
      antiarrhythmic activity using CaCl2-induced arrhythmia test. Compounds 4a, 4c and
      4f at lower doses completely protected the animals against the induced
      arrhythmias.

PMID- 9035555
TI  - Formulation of aspirin-magaldrate double-layer tablets: in vitro evaluation and
      cytoprotective activity in rats.
AB  - Double layer 325 mg oral aspirin tablets buffered with magaldrate antacid, 100,
      150, 175 and 200 mg (F1, F2, F3 and F4, respectively) were prepared by direct
      compression. The new formulae were of remarkable hardness and friability. The
      tablets complied with the requirements of the acid neutralizing capacity,
      uniformity of dosage units, disintegration and dissolution tests (USP XXIII) for
      buffered aspirin tablets. The in vitro release pattern of F1 and F1 followed
      first order kinetics (r = 0.999), while F3 and F4 were released according to a
      zero order model (r = 0.993). Formulations F2, F3 and F4 as well as the marketed
      preparations, pure Aspro tablets (Acetylsalicylic acid 320 mg per tablet), or
      Ascriptin tablets (aspirin 325 mg plus 150 mg Maalox per tablet) were
      administered to fasted rats by gavage at doses that provided 400 mg aspirin kg-1
      and the extent of the induced gastric damage was quantified 6 h later. Ascriptin,
      F3 and F4 preparations produced significantly less gastric damage (p < 0.05, n =
      6) when compared with pure Aspro tablets. There was a clear dose-dependent
      decrease in the gastric damage following treatment with F2, F3 and F4
      preparations, but there was no significant difference between the effects of F3
      and F4 which were equipotent with Ascriptin.

PMID- 9035556
TI  - Studies on arylfuran derivatives--Part V. Synthesis and antibacterial properties
      of 7H,6-[5-(4-nitrophenyl)-2-furyl]-1,2,4-triazolo [3,4-b]-1,3,4-thiadiazines.
AB  - The preparation of fifteen new 7H, 6-[5-(4-nitrophenyl)-2-furyl]-1,2,4
      triazolo[3,4-b]-1,3,4-thiadiazine is described. The structural elucidation of all
      the compounds is carried out on the basis of analytical and spectral data. The
      newly synthesized compounds are evaluated for their antibacterial activity
      against both Gram-positive and Gram-negative bacteria.

PMID- 9035557
TI  - Evaluation of some acylamide derivatives as potential hypoglycemic agents.
AB  - A series of new acylamide derivatives with piperidine, pyrrolidinyl and alanyl
      have been tested for their hypoglycemic activities. 2-(Pyrrolidynyl)-N-(3
      chlorophenyl) acetamide and 2-(Piperazinyl)-N-(4-methoxy phenyl) acetamide were
      found most active hypoglycemic compounds. Probably the amides have mode of action
      similar to sulphonylureas.

PMID- 9035558
TI  - Synthesis and biological activity of some pyrimidine derivatives.

PMID- 9035559
TI  - Status of free radicals and their scavenging enzymes in pregnancy induced
      hypertension (PIH).
AB  - The levels of lipid peroxidation (malonaldialdehyde), one of the consequence of
      free radical damage, and the antioxidant enzymes superoxide dismutase and
      catalase were estimated in the blood samples of fourteen normal and thirteen
      pregnancy induced hypertensive patients. A marked increase in malonaldialdehyde
      (p < 0.001) with concomitant decrease in superoxide dismutase (p < 0.001),
      catalase (p < 0.001) activities were observed in PIH as compared to normal
      pregnancy, thereby indicating the involvement of free radicals in PIH.

PMID- 9035560
TI  - One pot synthesis of some new substituted hexahydro 2H-1,3-benzoxazine
      derivatives.
AB  - In this paper, we synthesized nineteen new compounds having 2,4-diaryl-5
      oxohexahydro-2H-1,3-benzoxazine structure by the reaction of 1,3
      cyclohexanedione, aromatic aldehyde and ammonium acetate. In addition, we
      evaluated calcium antagonistic activity of these compounds versus nicardipine.

PMID- 9035561
TI  - Determination of selenium in plasma, urine and tissues, of standard diet-fed rats
      and dogs by ETA-atomic absorption spectroscopy with Zeeman background correction.
AB  - The method described was developed to be applied in determination of selenium in
      biological matrices (plasma, urine and tissues) using ETA-AAS with Zeeman
      background correction. These matrices were obtained from non-fasting S.D. rats
      and Beagle dogs of both sexes in order to acquire data on the endogenous levels
      of selenium in these laboratory animals when fed with standard diets. For tissue
      digestion, a simple procedure using the strong organic base, Soluene 350, was
      adopted. Precision assays were carried out monitoring Se(IV) levels in spiked
      matrices (range from 25 to 200 ng) and obtaining relative standard deviations
      (RSD%) in the range from 3.2% to 14.5% (intra-day) and from 7.6% to 15.9% (inter
      day). Accuracy assays gave relative errors (RE%) in the range from -6.5 to 4.2%
      (intra-day) and from -5.5% to 5.7% (inter-day). The validity of the method was
      checked on reference material (NBS SRM 1577 bovine liver) and the values obtained
      correlated with the certified ones. The detection limit assumed was 0.9 ng/ml,
      whereas the quantitation limit of selenium in matrices ranged from 2 to 5 ng/ml
      (or g), depending on the kind of sample.

PMID- 9035562
TI  - Role of the hypoglycemic plant extract cleome droserifolia in improving glucose
      and lipid metabolism and its relation to insulin resistance in fatty liver.
AB  - In this work the mechanism of the hypoglycemic effect of the plant Cleome
      Droserifolia (C.d.) was studied in a group of albino rats rendered glucose
      intolerant by tetracycline (T.) induced fatty liver, and compared with a normal
      control (C.) rats. The plant extract significantly suppressed the rise in
      peripheral blood glucose concentrations, both in the basal (fasting) state and
      after glucose intake. Suppression of basal blood glucose indicated a lowering
      effect of the plant extract on hepatic glucose output (HGO). The postprandial
      hypoglycemic effect of the plant extract without increasing insulin secretion was
      explained by; First: Potentiation of peripheral and hepatic insulin sensitivity.
      Second: by diminishing intestinal glucose absorption, which was evident by
      blunting plasma glucose levels throughout the oral glucose challenge. This plant
      might prove to have a promising therapeutic value in the treatment of diabetes
      mellitus, for besides its postprandial hypoglycemic effect, its suppression to
      hepatic glucose output in the fasting state is a beneficial therapeutic finding
      in favour of the plant as insulin is the most important drug that brings about
      this effect. The plant has also got a hypocholesterolemic effect more
      specifically on low density lipoprotein cholesterol (LDL-C) which consequently
      raised the high density lipoprotein cholesterol/low density lipoprotein
      cholesterol (HDL-C/LDL-C) ratio. This adds to its value as a protective and
      antiatherogenic agent.

PMID- 9035563
TI  - Mechanism of insulin resistance and hyper-insulinemia in fatty liver.
AB  - Hyperinsulinemia and insulin resistance are common features seen in most liver
      diseases. The present study was carried out on an experimental model of fatty
      liver (tetracycline induced) in albino rats. Significantly elevated levels of
      both peripheral plasma insulin and plasma glucose concentrations were recorded in
      both the fasting state and after an oral glucose intake in the tetracycline
      treated rats. The presence of hyperinsulinemia accompanying hyperglycemia is
      considered a sign of insulin resistance. Peripheral insulin resistance has been
      proved in this work by the reduced "A" value which refer to the peripheral
      insulin activity (sensitivity) in fatty liver rats compared to normal rats. The
      hyperinsulinemia recorded here was due to pancreatic hypersecretion and not a
      result of reduced hepatic degradation. Hypersecretion of insulin was clearly
      determined by measuring the level of immunoreactive insulin (IRI) in pancreatic
      vein which exhibited a significant rise in tetracycline-treated rats, and there
      was a positive correlation between the pancreatic venous and peripheral venous
      insulin in the basal state and after 30 min. of oral glucose administration.
      Hepatic degradation of insulin was not a cause as evidenced by First: the amount
      of insulin secreted and insulin consumed were significantly higher in fatty liver
      rats than normal controls. Second: the whole body extraction ratio or insulin
      degradation was not significantly different in the tetracycline-treated rats from
      the normal rats. The present data suggests that insulin resistance and
      hyperinsulinemia underlie the observed metabolic disturbances that characterize
      fatty liver disease.

PMID- 9035564
TI  - Toxic metabolites from phytopathogenic Ascochyta species.
AB  - We review some chemical and biological aspects of toxic metabolites produced in
      vitro by phytopathogenic Ascochyta species, fungi having agrarian and
      toxicological importance. In particular, here the isolation of some known and new
      cytochalasins from A. heteromorpha and A. lathyri, four new nonenolides from A.
      pinodes and a new trisubstituted derivative of salycilic aldehyde from A. pisi
      are described. Furthermore, the identification of medicarpin, phytoalexin found
      in the chickpea seeds naturally infected by A. rabiei is also reported.

PMID- 9035565
TI  - [Who's afraid of the big bad wolf? Asymptomatic Wolf-Parkinson-White syndrome:
      should we intervene?].

PMID- 9035566
TI  - [Medicine and the Internet].

PMID- 9035567
TI  - [Acute fulminant hepatitis].

PMID- 9035568
TI  - [Lipid-laden alveolar macrophages as markers of gastro-esophageal reflux in
      pulmonary disease in childhood].

PMID- 9035569
TI  - [Non-pharmacological control of hypertension].

PMID- 9035570
TI  - [Lipoprotein (a) as a cardiovascular risk factor in man].

PMID- 9035571
TI  - [Superoxide dismutase and the eye].

PMID- 9035572
TI  - [Treating polymyositis: methotrexate or azathioprine?].

PMID- 9035573
TI  - [The care of the adolescent--ethical issues].

PMID- 9035574
TI  - [Acute renal failure and fatal respiratory failure in leukemic
      hyperleukocytosis].

PMID- 9035575
TI  - [Prognostic factors and surgical results in traumatic cataract].
AB  - The visual outcome in 23 men and 2 women with traumatic cataracts was analyzed
      retrospectively. Their average age was 33 and they ranged from 10 to 69 years.
      Surgical results were either very good or very poor. Associated retinal injuries
      significantly decreased final visual acuity (p = 0.001). Those with initial
      visual acuity restricted to finger counting had better visual results than those
      with initial visual acuity restricted to light perception (p = 0.01) and hand
      motions (p = 0.02). Usually the lens was removed via the pars plana; the most
      common mode of optical correction was contact lenses.

PMID- 9035576
TI  - [Hyperbaric oxygen for carbon monoxide poisoning].
AB  - Severe cases of carbon monoxide (CO) poisoning from all over Israel are treated
      at the Israel Naval Medical Institute with hyperbaric oxygen (HBO). Between
      1.11.94 and 15.2.95. 24 cases of CO poisoning were treated. Poisoning was usually
      due to domestic gas-fired heating systems, CO being the only toxin involved.
      Since delay between termination of CO exposure and arrival at the emergency
      department averaged 55 minutes, the level of carboxyhemoglobin measured on
      presentation did not always reflect the true severity of the poisoning. Poisoning
      was defined as severe and requiring HBO treatment when 1 or more of the following
      indications was present: evidence of neurological involvement, cardiographic
      signs of acute ischemic injury, metabolic acidosis, carboxyhemoglobin level
      greater than 25%, and pregnancy. 20 (84%) recovered consciousness during the
      course of 1 session (90 min.) of HBO treatment (pO2 2.8 ATA) or immediately
      thereafter, with resolution of other signs of CO poisoning. 3 required a second
      treatment session before their symptoms resolved. A patient who arrived in deep
      coma with severe cerebral edema died. HBO is an important element in the combined
      treatment of severe CO poisoning. There should be greater awareness of the danger
      of CO poisoning and the means of preventing it, both among medical staff and the
      population as a whole, mainly in areas in which cold weather requires use of
      heating systems, which may be gas-fired.

PMID- 9035577
TI  - [The serotonin syndrome].
AB  - The frequent use of selective, serotonin reuptake inhibitors has increased the
      risk of the serotonin syndrome. This condition is related to stimulation of 5HT1A
      receptors and is characterized by agitation, confusion, tremor, fever and
      shivering. A 29-year-old woman and a 69-year-old man with the syndrome are
      reported. The importance of early diagnosis and treatment is emphasized, and
      aspects of the syndrome in patients with obsessive-compulsive disorder are
      presented.

PMID- 9035578
TI  - [The homeless and the health system: profile of the homeless patient].
AB  - The homeless population is mobile and does not use ambulatory health care
      services. Thus the major contact between the homeless and the medical
      establishment occurs primarily when they are treated for acute symptoms in
      hospital. We describe the clinical and sociodemographic profile of the homeless
      who require hospital services. The research population included 50 homeless
      treated in the emergency room and various departments of our medical center
      between October 1994 and August 1995. Social workers used a questionnaire
      relating to clinical, sociodemographic and social factors. Most patients were
      men, 76% under the age of 50. The most common diagnosis was alcoholism; other
      diagnoses included back, limb and joint injuries, infections, skin diseases, and
      general exhaustion. There were subgroups with differing needs within this
      homeless population for which appropriate rehabilitation programs are proposed.

PMID- 9035579
TI  - [Differentiated thyroid cancer in Arabs in northern Israel].
AB  - Prognostic factors and survival rate of 53 Arabs with differentiated carcinoma of
      the thyroid treated here were reviewed. Papillary carcinoma was diagnosed in 35
      (66%) and follicular carcinoma in 18 (34%): the female/male ratio was 2.3/1 and
      the median age 32. Age, gender, tumor size, histology and tumor stage were
      important prognostic factors. The 20-year actuarial survival rate of the entire
      group was 96%. The probable reason for the high survival rate was the low median
      age.

PMID- 9035580
TI  - [Rheumatoid arthritis in the elderly].
AB  - Opinions differ as to whether late onset rheumatoid arthritis (RA) represents a
      clinical subset and whether age at onset involves differences in therapy and
      prognosis. In this retrospective study we compared 23 patients with early onset
      RA (average onset 52.8 years; 91.3% of them women), with 36 with late onset
      (average onset 70.3 years; 67% of them women). No statistically significant
      differences were found as to demographic, clinical, laboratory or radiographic
      characteristics.

PMID- 9035581
TI  - [Temporal hemianopia and diabetes insipidus following head injury].
AB  - Bitemporal hemianopia and diabetes insipidus following head injury are caused by
      a lesion in the center of the optic chiasm, together with injury to the adjacent
      pituitary stalk or the hypothalamus. This combination was thought to be a rare
      complication of severe head injury. The case of a 16-year-old male is presented,
      which together with recent reports suggests that this relatively under-recognized
      syndrome is not infrequent, that it may follow even minor head injury, and that
      magnetic resonance imaging can demonstrate the chiasmal lesion.

PMID- 9035582
TI  - [Motor vehicle accidents and eye injuries].
AB  - The medical records of 24,632 patients treated in our surgical emergency service
      over a 3-year period were reviewed to determine the frequency and characteristics
      of ocular trauma caused by motor vehicle accidents (MVA). MVA-related injuries
      accounted for 13.9% of all visits to the service and involved 1106 of the
      patients (33%), of whom 77% were young males. At least 1 pathological finding was
      found in 858 (77.6%) and 169 (15.2%) were admitted. 16 patients sustained very
      severe ocular injuries which resulted in poor vision.

PMID- 9035603
TI  - The JIM interview. Harry Kimball, MD.

PMID- 9035604
TI  - Protective and pathogenic roles of cytokines in inflammatory bowel diseases.

PMID- 9035605
TI  - A biochemical perspective of methotrexate neurotoxicity with insight on nonfolate
      rescue modalities.

PMID- 9035606
TI  - Therapeutic potential of neutrophil-elastase inhibition in pulmonary disease.

PMID- 9035607
TI  - Leptin, its receptor and obesity.

PMID- 9035608
TI  - Metabolic characterization of long-term successful pancreas transplants in type I
      diabetes.
AB  - BACKGROUND: The encouraging results of the Diabetes Control and Complications
      Trial emphasize the need for improved methods of glycemic control to prevent the
      potentially devastating complications of Type I diabetes mellitus. However,
      current conventional approaches have failed to consistently achieve normal HbAlc
      levels and increase the risk of hypoglycemia. Pancreas transplantation is a
      consistently reliable method of achieving postoperative normal glucose levels,
      but no extensive assessment has been made of the long-term stability of its
      metabolic benefits. METHODS: To ascertain long-term stability of metabolic
      function of pancreas transplants in Type I diabetic patients, we studied fasting
      glucose levels, glucose disposal after intravenous glucose challenge, HbAlc
      levels, and pancreatic islet beta and alpha cell responsiveness in a series of 96
      successfully transplanted recipients. Patients were studied cross-sectionally
      and, when possible, longitudinally for up to five years post-transplantation.
      Special emphasis was given to the longitudinal analysis to determine whether
      initial metabolic benefits maintain stability or undergo deterioration during the
      first five postoperative years. RESULTS: Pancreas transplantation was accompanied
      by normal or nearly normal fasting plasma glucose levels, intravenous glucose
      disappearance rates, and HbAlc levels. Beta cell function assessed by acute
      insulin responses and acute C-peptide responses to intravenous glucose injections
      revealed no deterioration in the magnitude of these responses. Analysis of acute
      insulin and C-peptide responses to intravenous arginine provided similar results.
      Alpha cell function, assessed by measuring acute glucagon responses to
      intravenous arginine, were significantly (p > .001) greater than preoperative
      responses and remained stable over the ensuing five-year period. In grafts that
      maintained function, none of these metabolic measures showed deterioration during
      the five-year postoperative period. CONCLUSIONS: Successful pancreas
      transplantation provides pancreatic islet function that results in normal or near
      normal glycemic control for up to five years postoperatively in Type I diabetic
      recipients receiving no exogenous insulin or oral hypoglycemic agent therapy.

PMID- 9035609
TI  - Effects of low density lipoprotein on cytosolic [Ca++] in cultured rat mesangial
      cells.
AB  - BACKGROUND: Recently, a low density lipoprotein (LDL) receptor has been
      identified in mesangial cells. However, the nature of intracellular signals in
      mesangial cells after exposure to LDL is unclear. METHODS: We studied the effect
      of LDL on cultured rat mesangial cell [Ca++]i using spectrofluorometry. RESULTS:
      Addition of LDL (15 micrograms/mL) produced a rapid, transient, and dose
      dependent rise in [Ca++]i within seconds, returning to baseline in 6 minutes. No
      further rise was observed at higher LDL concentrations. No significant rise in
      [Ca++]i was observed with LDL in cells placed in a Ca(++)-free medium. The
      [Ca++]i rise was greatly attenuated in magnitude and duration when lanthanum was
      used. In contrast, verapamil failed to block the LDL-induced rise in [Ca++]i.
      Addition of LDL did not alter production of inositol 1,4,5-triphosphate (IP3) by
      mesangial cells. CONCLUSIONS: Low density lipoprotein caused a transient rise in
      [Ca++]i in cultured rat mesangial cells. The observed rise in [Ca++]i was largely
      caused by influx of extracellular Ca++ through receptor-gated channels.
      Mobilization from intracellular stores and activation of IP3 were not involved.
      The rise in [Ca++]i may mediate the effects of LDL on mesangial cell function.

PMID- 9035610
TI  - Platelet inhibitory effect of nitroglycerin in platelet-rich plasma: relevance of
      glutathione-s-transferases in plasma.
AB  - BACKGROUND: Nitroglycerin (NTG) is believed to exert its platelet inhibitory
      effect via its biotransformation to nitric oxide (NO). We examined the relevance
      of glutathione-s-transferases (GST) in plasma in the conversion of NTG to NO and
      the platelet inhibitory effect of NTG. METHODS AND RESULTS: Nitroglycerin (1-100
      micrograms/mL) was incubated with human platelet-rich plasma (PRP) for 10-60
      minutes. Nitroglycerin caused a concentration-dependent inhibition of platelet
      aggregation in PRP with IC50 approximately 50 micrograms/mL. NTG also enhanced
      nitrite levels in PRP and stimulated cyclic GMP accumulation in platelets. In
      contrast, when NTG was incubated with washed platelets (WP) in concentrations as
      high as 100 micrograms/mL, there was no inhibition of platelet aggregation,
      formation of nitrite, or accumulation of cGMP. However, treatment of WP
      suspension with authentic NO exhibited diminished platelet aggregation,
      suggesting that NTG delivers NO in plasma that subsequently inhibits platelet
      aggregation. In keeping with this concept, the aggregation inhibitory effect of
      NTG in PRP was blocked by oxyhemoglobin. The platelet aggregation inhibition by
      NTG was potentiated by propylthiouracil (600 micrograms/mL), a GST inducer, and
      antagonized by ketoprofen (100 micrograms/mL), a GST inhibitor. Direct
      measurement indeed showed significant GST activity in plasma (24 +/- 3 mU/mL).
      CONCLUSIONS: We suggest that NTG inhibits platelet aggregation in PRP by its
      biotransformation to NO in plasma. The presence of GST, and perhaps other
      cofactors, in plasma is relevant in the platelet inhibitory effects of NTG in
      PRP.

PMID- 9035611
TI  - Evidence for the involvement of protein kinase C isoforms in alpha-1 adrenergic
      activation of phospholipase A2 in FRTL-5 thyroid cells.
AB  - BACKGROUND: FRTL-5 thyroid cells are a cell line extensively used for the
      investigation of thyroid functions. Activation of alpha-1 adrenergic receptors
      stimulates both arachidonic acid (AA) release and cytosolic Ca2+ increase in this
      cell line. Cytosolic Ca2+ and arachidonic acid are known to be important second
      messengers regulating a variety of thyroid functions. The generation of these
      messengers is regulated primarily by two different types of phospholipases,
      phospholipase C (PLC) and phospholipase A2 (PLA2). METHODS: Norepinephrine (NE,
      10 mumol/L) was used as an alpha-1 adrenergic activator, and cytosolic-free Ca2+
      concentration ([Ca2+]i) was determined using the fluorescent dye indo-1.
      Arachidonic acid release was measured as an indicator of PLA2 activation, and
      protein kinase C (PKC) activity determination and isoforms identification were
      performed using commercial kits. RESULTS: Norepinephrine increased [Ca2+]i and AA
      release. Prevention of NE-induced cytosolic Ca2+ influx, either by removal of
      extracellular Ca2+ or by use of Ca2+ channel blockers, NiCl2 or CoCl2, inhibited
      AA generation entirely. Inhibition of NE-induced increase in [Ca2+]i by the Ca2+
      chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), also
      significantly suppressed NE-induced AA release. Inhibition of PKC activity by PKC
      inhibitors (H-7 or staurosporine) or downregulation induced by prolonged
      treatment with phorbol 12-myristate 13-acetate (PMA) or thyleametoxin (TX)
      significantly blocked the NE-induced AA release, which indicates PKC is involved
      in mediating NE-induced AA release. Protein kinase C activity measurement
      indicated that NE induced an activation of PKC in 5 minutes. To further
      characterize the role of PKC or Ca2+ in regulation of AA release, we identified
      PKC isoforms by immunoblotting with specific antibodies against 8 different
      Protein kinase C isoforms. PKC-alpha, -beta I, -beta II, -gamma, delta, -epsilon,
      -zeta, and -eta isoforms were identified. Norepinephrine induced translocation of
      PKC-alpha, -beta I, -beta II, -gamma, -delta, and -epsilon isoforms but not -zeta
      and -eta from cytosol to membrane. Chelation of intracellular Ca2+, prevention of
      Ca2+ influx, or prolonged treatment with thymeleatoxin (TX) completely blocked
      the NE-induced translocation of PKC-alpha. CONCLUSIONS: These results, taken
      together with data obtained from AA experiments, suggest that PKC plays a
      critical role in alpha-1 adrenergic receptor mediated PLA2 activation and
      subsequent AA release. Extracellular Ca2+ influx is a prerequisite for both PKC
      alpha translocation and AA release. Whether Ca2+ acts directly upon the PLA2, or
      via PKC-alpha, to regulate AA generation is an intriguing question that remains
      to be clarified.

PMID- 9035612
TI  - Cardiac endothelin release and infarct size, myocardial blood flow, and
      ventricular function in canine infarction and reperfusion.
AB  - BACKGROUND: The potent vasoconstrictor endothelin-1 (ET) may play an important
      pathophysiologic role in acute myocardial infarction, but its precise effects are
      incompletely understood. The purpose of this study was to evaluate the
      interrelationships between cardiac ET-1 release and infarct size, myocardial
      blood flow, and ventricular function. METHODS: Fifteen closed chest dogs
      underwent 3 hours of coronary artery occlusion followed by 3 hours of
      reperfusion. Coronary sinus and aortic ET-1 levels during occlusion and after
      reperfusion were determined by radioimmunoassay. Left ventricular function and
      regional myocardial blood flow were measured by echocardiography and colored
      microspheres, respectively. Myocardial infarct size was determined by postmortem
      staining with blue dye and triphenyl tetrazolium chloride. RESULTS: Coronary
      occlusion and reperfusion produced significant elevations of coronary sinus ET-1
      (p < 0.05) and cardiac ET-1 release (p < 0.05), and a trend toward an increase in
      aortic ET-1 (p = 0.08). A trend toward more ET-1 release was observed in dogs
      with larger infarcts (p = 0.06), and in dogs with substantial no-reflow in the
      reperfused territory (p = 0.05). Endothelin-1 release also was associated with
      increased contractility in nonischemic myocardial segments (p = 0.002), and ET-1
      correlated with increased global left ventricular function (p < 0.02).
      CONCLUSIONS: In this canine model of coronary occlusion and reperfusion, greater
      increases in cardiac ET-1 release were observed in dogs with larger infarcts, and
      increased ET-1 release was associated with the no-reflow phenomenon in the
      reperfused territory. These data suggest that ET-1 release may have adverse
      consequences in acute myocardial infarction, including a reduction of myocardial
      blood flow in the reperfused zone after reperfusion and increased contractility
      in nonischemic myocardium.

PMID- 9035613
TI  - Mechanisms of amiodarone-induced inhibition of Ca2+ current in isolated neonatal
      rabbit ventricular myocytes.
AB  - BACKGROUND: Amiodarone is an effective antiarrhythmic drug used to treat a wide
      variety of ventricular and supraventricular tachyarrhythmias. Recent voltage
      clamp studies indicate that amiodarone may possess a variety of antiarrhythmic
      effects. METHODS: The tight-seal, whole-cell voltage clamp technique was used to
      investigate the acute effects of amiodarone on L-type Ca2+ channel kinetics in
      isolated neonatal ventricular myocytes. RESULTS: We found that acute perfusion
      with 1 mumol/L amiodarone inhibited peak inward Ca2+ current by 39.1% (4.85 +/-
      0.42 to 2.95 +/- 0.6 pA/pF, n = 10, p < 0.001) without changing the shape of the
      current-voltage relation. In addition, amiodarone shifted Ca2+ channel steady
      state inactivation to more negative membrane potentials. In the absence of
      amiodarone, half inactivation of the Ca2+ current occurred at a membrane
      potential of -23.8 +/- 0.2 mV compared to -34.2 +/- 0.6 mV after addition of
      amiodarone (n = 11, p < 0.01). Furthermore, amiodarone significantly delayed Ca2+
      current recovery from previous inactivation. CONCLUSIONS: These results provide
      evidence that amiodarone blocks voltage-dependent Ca2+ current in isolated
      neonatal rabbit ventricular myocytes by a variety of different mechanisms. The
      inhibitory effect of amiodarone on L-type Ca2+ current may represent an important
      facet of amiodarone's acute antiarrhythmic activity in the immature heart.

PMID- 9035614
TI  - Sources for a Galenic visual theory in late thirteenth century.

PMID- 9035615
TI  - Modification of dental mirrors and retractors for intra-oral photography.

PMID- 9035616
TI  - Teaching about the female condom.
AB  - Reality female condoms became available for over-the-counter purchase in the fall
      of 1994. Because the female condom is a new sexual barrier device, women need to
      learn how to use it correctly. Health care providers must also be knowledgeable
      about the correct use of the female condom so that they can teach women how to
      use it as a barrier method. To facilitate learning about the female condom, a
      curriculum was developed that included a quiz on knowledge about the female
      condom. Content validity was established through a content validity index
      completed by six content experts. This quiz was used to evaluate educational
      sessions offered to 42 persons in an urban college setting and 18 women in a
      community setting. The article describes the female condom along with the
      curriculum that was developed to teach its correct use and the reactions of
      potential users of the female condom.

PMID- 9035617
TI  - Human immunodeficiency virus infection risk among female sex partners of
      intravenous drug users in southern Arizona.
AB  - Epidemiologic data suggest that women who are sexual partners of intravenous drug
      users (IVDUs) are at increasing risk for infection with human immunodeficiency
      virus (HIV). The article reports a study describing living conditions, sex risk
      behaviors, knowledge about acquired immunodeficiency syndrome (AIDS), and
      perceptions of AIDS risk among female sexual partners of IVDUs living in southern
      Arizona. One hundred and twenty-three women who did not use IV drugs but had had
      sex with an IVDU in the last 6 months were interviewed. Eighty percent belonged
      to an ethnic minority, and 20% were white. Condom use was infrequent regardless
      of the number of sexual contacts. Sex was primarily heterosexual, with unsafe
      vaginal intercourse being the most common practice. Barriers to condom use were
      self-related and partner related. Some women lacked knowledge about sexual
      transmission of AIDS. All women reported getting AIDS information in the last 6
      months and felt some risk of contracting the disease. AIDS risk reduction
      interventions should include HIV education and focus on barriers to condom use.

PMID- 9035618
TI  - Self-care activities of women infected with human immunodeficiency virus.
AB  - The article describes a qualitative focus group study exploring the self-care
      activities undertaken by women testing positive for human immunodeficiency virus
      (HIV) to promote and maintain their health. The sample included 27 women who
      participated in one of four focus group sessions. Participants represented women
      from both rural and urban settings in the South. Subjects talked about and
      described the ways in which they took care of themselves. Content analysis was
      used to code the data and to determine major categories of activities. Seven
      categories were identified: special dietary and nutrition practices, choosing not
      to use medically prescribed therapies, spiritual reliance and rituals, staying
      active, cognitive strategies, self-education, and adopting healthy life styles.
      These findings support the value of developing a holistic approach to health care
      of women infected with HIV.

PMID- 9035619
TI  - Going home: African-American caregiving for adult children with human
      immunodeficiency virus disease.
AB  - The caregiving literature has focused on European-American caregivers who are
      providing care to spouses or parents with Alzheimer's disease. The article
      reports ethnographic research exploring aspects of caregiving by rural African
      American mothers for adult children with human immunodeficiency virus (HIV)
      disease. Eight African-American mothers were interviewed to elicit cultural
      domains of caregiving. Two major domains were a personal relationship with God
      and God's will. Taken together, these domains framed the context in which African
      American mothers understood HIV disease, provided care, and resolved the death of
      their adult child.

PMID- 9035620
TI  - Attitudes, concerns, and fear of acquired immunodeficiency syndrome among
      registered nurses in the United States.
AB  - The article reports a study describing nurses' attitudes, concerns, and fear of
      acquired immunodeficiency syndrome (AIDS). A convenience sample consisting of 376
      nurses in a mid-Atlantic state was drawn. An 84-item questionnaire was used to
      collect the data. Seven factors were derived from the subjects' responses using
      the Fear of AIDS Scale II: opinion and AIDS policy, blood and physical closeness
      to patients with AIDS, punishing the homosexual, ethics of care. "Who would care
      for me?" financial burden, and self-worth. Fear of AIDS Scale II scores ranked
      the highest whenever "self" was involved with AIDS issues or blood and physical
      closeness to a person with AIDS. There was a parallel increasing relationship
      between concern about contracting AIDS from patients and the fear of AIDS. A
      number of other significant correlations emerged from the study.

PMID- 9035621
TI  - Battered women's perceptions of loss and health.
AB  - The article reports a study investigating whether a positive relationship exists
      between a battered women's perceptions of loss and her perceptions of health. The
      study further investigated whether a period of time away from the abusive
      situation would change the battered women's perceptions of loss and her
      perceptions of health. A convenience sample of 20 women who had experienced
      battering and abuse and had sought help at a protective shelter was studied.
      Questionnaires on perception of loss, health response, and demographics were used
      for the collection of data. The findings indicated that a significant
      relationship exists between a battered women's perceptions of loss and her
      perception of health. Perceptions of loss and health were shown to decline after
      a period of 5 days away from the abusive situation. Additional qualitative data
      obtained from in-depth interviews were also found to be consistent with the
      quantitative results and supported the literature documented in this study.

PMID- 9035622
TI  - Assessing abuse in female suicide survivors.
AB  - The article reports a study examining the level of rejection of the suicide
      victim by the surviving widow and the suicide survivor's experiences of abuse.
      The 49 female suicide survivors who participated in this study were part of a
      larger nursing postvention study. Descriptive statistics and the nonparametric
      Spearman correlation for a two-tailed test (a < 0.05) were used to analyze the
      data. Results showed that 65.3% of the survivors of suicide had experienced some
      form of abuse, the most frequent being verbal abuse. Experiences of abuse may
      affect the bereavement process and coping strategies in surviving the suicide of
      a spouse.

PMID- 9035624
TI  - Acute respiratory distress syndrome: an overview.
AB  - Acute Respiratory Distress Syndrome (ARDS) is a fulminant form of respiratory
      failure which has diverse aetiology. Although the pathophysiology of the disease
      is understood in some depth today, much is still elusive and, despite
      technological advances in intensive care medicine, mortality rates remain high.
      This article focuses on the key areas of: the inflammatory processes in ARDS, the
      altered pulmonary physiology, and finally the outcomes, treatments and the need
      for future research. A knowledge of these aspects is useful to intensive care
      nurses.

PMID- 9035623
TI  - Stress, hope, and well-being of women caring for family members with Alzheimer's
      disease.
AB  - The article describes a study that tested a midrange model of caregiver stress
      mediation in women caring for a family member with Alzheimer's disease. The study
      was grounded in the nursing theory of modeling and role modeling and tested two
      hypotheses based on theoretically derived propositions. A convenience sample of
      88 female caregivers participating in a larger study completed measures of
      perceived stress, hope, and well-being. Significant correlations among the three
      variables occurred in the expected directions. Hope was found to mediate the
      relationship between stress and well-being, providing tentative support for the
      theoretically proposed linkages.

PMID- 9035625
TI  - Alleviating anxiety in nursing patients' significant others.
AB  - This paper describes an investigation of factors that help to alleviate anxiety
      in nursing patients' significant others, based on the assumption that anxiety
      flows from the feeling of insecurity and accordingly that anxiety can be
      alleviated by strengthening the sense of security. The focus of the study is on
      factors that affect experiences of security in the significant others of
      critically ill patients. In addition, the paper addresses the questions of how
      the age and gender of the significant other, the duration of intensive care, and
      the patient's named nurse influence the assessments by significant others of the
      quality of the nursing care provided. Fourteen significant others of critically
      ill patients took part. The data were collected in focused interviews. For
      qualitative analysis the raw data were analysed into four main themes: nurse
      characteristics, interaction, professional competence, and confidence in nursing
      care and in the nursing staff. In the quantitative analysis the concern was with
      how these themes and their subcategories were emphasised by participants and on
      different variables. Frequencies were used. According to the results, significant
      others considered it important to have close contact with the nursing staff. Each
      patient's named nurse had an important role to play in improving the quality of
      nursing care. In general, respondents appeared to consider that factors which had
      to do with attitudes, which could be subjectively evaluated and which were not
      objectively discernible, were the most important determinants of safe, quality
      nursing care.

PMID- 9035626
TI  - Media enquiries and nurses.
AB  - In this article, the legal and professional implications surrounding
      'confidentiality' and in particular confidentiality with regards to dealing with
      media enquiries are considered; and professional and legal responsibilities and
      problem areas for nurses are outlined. The use of specific policies which give
      instruction on dealing with media enquiries is also discussed.

PMID- 9035627
TI  - The intensive care units in greater Athens: needs and resources.
AB  - The purpose of this study was to investigate the availability of intensive care
      unit (ICU) beds and the number of requests, the number and categories of nursing
      staff, the nursing care required, and the time spent in various nursing
      activities. METHODS: 19 district general hospitals were studied. The
      characteristics of the units and their nursing personnel were recorded. The
      availability of ICU beds, the frequency of bed requests, and the way of patient
      admission in the ICUs were studied retrospectively for 1 year and prospectively
      for 2 weeks. The staffing level of direct care for 36 patients was studied to
      determine the time required for direct nursing care. RESULTS: the distribution of
      intensive care beds was: GICU 108, CICU 114, PSICU 30. During 1991, 12363
      patients were admitted and 12172 of them were discharged; 3 628 patients stayed
      less than 2 days while the average length of stay was 12.5 days. In 1992, during
      the 2-week period, there were 303 requests for an admission to ICUs and of these
      150 requests could not be met because of lack of ICU beds. The mean staffing
      level was 2.3 nurses per bed (to cover the three shifts). The mean nursing time
      required for direct nursing care of each patient per shift was found to be 6
      hours for GICU patients, 5.3 for CICU, and 6.0 for PSICU patients.

PMID- 9035628
TI  - The complexity of pain assessment and management in the first 24 hours after
      cardiac surgery: implications for nurses. Part 2.

PMID- 9035629
TI  - Communicating with sedated ventilated patients in intensive care: focusing on the
      use of touch.
AB  - Communication with intensive care patients is of paramount importance, especially
      when communicating with a critically ill patient who is sedated and ventilated,
      and therefore unable to speak. Disclosure under these circumstances is extremely
      difficult, so in this situation touch is a valuable means of conveying messages.
      Consequently, touch as a way of communicating is discussed in this paper,
      highlighting the advantages and disadvantages. Barriers to communication in this
      environment are also discussed.

PMID- 9035630
TI  - Implementing change in the management of postoperative pain.

PMID- 9035631
TI  - Gentamicin once a day.
AB  - Almost 30 years after its introduction, gentamicin continues to play a key role
      in the treatment of gram negative sepsis. Once-daily dosing may offer a more
      effective, safer and economic use for this important antibiotic.

PMID- 9035632
TI  - Reflecting on the past.

PMID- 9035633
TI  - Towards an understanding of the human resource in the context of change in the
      NHS: economic sense versus cultural sensibilities?
AB  - The concepts involved in the process of managing change successfully in respect
      of the management of human resources are as complex as they are contentious, with
      arguments and counter-arguments espoused weekly in the seemingly ever-growing
      plethora of literature available. The following paper attempts to present a
      critical analysis of the management of change from the perspective of the human
      resource and to debate the relative merits pertaining to the imperatives of
      organizational design and culture, in conjunction with a plea to recognize and
      respect peoples' needs and feelings, in relation to the impact of internal market
      reform upon management practice within the context of the contemporary National
      Health Service (NHS). The paper is predicated upon the dual beliefs that people
      and organizations are dynamic entities being located both temporally and
      socially, and that any constructed criterions of success must, therefore, be
      evaluated not only in terms of the specific individual and/or organizational
      parameters but also in terms of the relative cultural, moral, philosphical and
      political ethos, and that as the human race largely survives and operates via
      organization, which in itself has to be managed, controlled and developed,
      managers are, therefore, a vital element of any successful organization.

PMID- 9035634
TI  - Confidential conversations between supervisor and employee as a means for
      improving leadership: a quasi-experimental study in hospital wards.
AB  - Although yearly confidential conversations between a supervisor and an employee
      have been recommended as a means for improving leadership, evidence on the actual
      effects of these conversations has been lacking. The present study therefore
      investigated whether confidential conversations improve perceptions of goal
      clarity, sufficiency of feedback and innovativeness, and elicit satisfaction with
      the supervisor's leadership style within the hospital setting. Nine wards were
      divided into one experimental group (3 wards) and two control groups (3 + 3
      wards). A questionnaire on goal clarity, feedback, innovativeness and
      satisfaction was administered twice to every group (1st measurement: r = 186, 2nd
      measurement: n = 163). The experimental group began confidential conversations
      after the first measurement, control group 1 entered into conversations during
      both measurements, and control group 2 did not enter into conversations at the
      time of either measurement. Confidential conversations improved perceived
      feedback. In both measurements, the sufficiency of feedback was reported to be
      significantly better in the groups having conversations than in the other groups.
      In addition, there was a significant positive change in the perceived sufficiency
      of feedback in the experimental group but not in the other groups. Confidential
      conversations did not affect the perceptions of goal clarity and innovativeness
      or elicit satisfaction with the supervisor's management style.

PMID- 9035635
TI  - Introducing a lecturer-practitioner: the management perspective.
AB  - The West Midlands Regional Health Authority Department of Nursing funded a 1-year
      study to look at 'Implementation aspects of the lecturer-practitioner role (in
      nursing)'. A feasibility study was carried out from November 1992 to October 1993
      to address the issue and highlight areas requiring more in-depth study. Twenty
      nine subjects working as or with lecturer-practitioners were interviewed using a
      semi-structured questionnaire. The interview was divided into two discrete parts.
      The first section contained a mixture of open and closed questions and the second
      section adopted a modified repertory grid technique. This paper provides the main
      results from the first half of the interview. The study describes in practical
      terms how managers need to plan for the introduction of a lecturer-practitioner
      post; the key responsibilities of the role; and a person specification. The work
      identifies clear prerequisite criteria for job role and gives guidance on
      lecturer-practitioner management and function.

PMID- 9035636
TI  - Who sets the business agenda?
AB  - Business planning is now a key activity in health care organizations and is
      affecting the way in which both managers and professionals carry out their work.
      This paper starts by examining some of the recent changes affecting business
      planning in a number of health care sectors. It then suggests that the business
      agenda can be based on four possible models-financial, marketing, needs or power.
      The evidence is examined, looking at input, output and process information, and
      some conclusions reached on what, in reality, influences the business agenda, as
      well as what doesn't, but perhaps should. The overwhelming importance of
      financial and power features of agenda setting are recognized and the paper
      concludes by suggesting how the contents of the agenda may be shifted by allowing
      the voices of a wider group of participants to be heard. Perhaps a new model will
      be developed based initially on information sharing but moving to real
      communication between the different perspectives now in existence.

PMID- 9035637
TI  - International communication: an investigation into the learning experiences of
      British and Russian student nurses.
AB  - Following student exchanges between The Northern College of Nursing in Salford
      and Medical College Number 1, St Petersburg, this study investigates the
      potential value of international communication for student nurses in both Russia
      and the United Kingdom. The purpose of the exchange was to maintain communication
      between the colleges and help with the development of their curriculum in post
      Soviet Russia. Whilst in England the 10 Russian students received practical and
      academic experience in medical, surgical, intensive care, accident and emergency,
      paediatric, mental health and community settings. Following interviews with four
      of the students certain issues central to their learning arose relating to the
      themes of education, resources, nursing practice and professional development.
      Additional to this the author, a mental health student, reflects on the value the
      exchange has had for his own learning focusing on areas of communication, self
      awareness and research. The implications of the exchange are discussed and the
      maintenance and further development of international communication is
      recommended. In conclusion it is suggested that work of this kind will add to the
      global development of the nursing profession.

PMID- 9035638
TI  - The future of ethnic minority nurses in the NHS.
AB  - The subject of discrimination especially with regard to the ethnic minority
      workforce in the NHS was the focus of a specially commissioned Task Force funded
      by the Department of Health and the King's Fund in 1991 followed by the PSI
      Report published last year to help health authorities to address racial
      discrimination. The first of these reports, for example, states quite clearly
      that 'racial inequalities between managers and staff in the service are
      glaring... black and ethnic minority staff will not join or remain in a service
      which they do not see to be providing good and fair employment prospects. This
      perhaps influenced the Secretary of State for Health, in 1993, to set up a
      programme of action which included a number of targets to be achieved. Goal
      seven, for example, specifically addresses nursing by stating that NHS
      authorities and trusts are to set local objectives to achieve representation of
      ethnic minority nurses at ward manager level within 5 years. This programme seems
      to focus on the issue of equal opportunities but although in does make reference
      to 'racial harassment' it does not include 'racism'. Hence the purpose of this
      paper is to address the issues of equal opportunities and anti-racism from a
      theoretical and practice base. It also intends to offer alternatives for the way
      forward by focusing on local initiatives.

PMID- 9035639
TI  - The basis of heredity: a genetic primer.
AB  - Traits seen in the neonate are a direct result of the expression of genes donated
      by parents at the time of conception. This article discusses the configuration of
      genetic material in humans, explains how an individual's genetic composition is
      unique, and demonstrates the importance of genetic information in determining
      traits related to health, disease, and individuality.

PMID- 9035640
TI  - The value of the white blood cell count and differential in the prediction of
      neonatal sepsis.
AB  - Infection is responsible for significant morbidity and mortality in high-risk
      neonates. Because infection has many nonspecific signs and symptoms, the neonatal
      nurse plays a crucial role in the early recognition of infection. The
      interpretation of the white blood cell (WBC) count and differential can be
      difficult and must take into account many factors, including gestational age,
      weight, and postconceptional age. This article focuses on those factors that
      affect WBC interpretation, as well as steps nurses can take to minimize specimen
      and sampling errors.

PMID- 9035641
TI  - Hematopoietic growth factors: Part II.
AB  - Anemia of prematurity (AOP) affects almost all infants that are born prematurely.
      Excessive phlebotomy in the NICU setting has exacerbated this condition. Until
      recently, erythrocyte transfusion has been the only therapy for AOP. Recombinant
      human erythropoietin (rh-EPO) has been shown to be effective in reducing
      erythrocyte transfusions in premature infants with AOP. Various studies have
      utilized rh-EPO as a treatment modality or as prophylaxis for AOP. The results of
      these studies have shown that rb-EPO is a complementary strategy along with
      restriction of phlebotomy and less liberal transfusion policies, to decreasing
      the number of transfusions that an infant may need. Trials are necessary to
      document the cost-effectiveness of rh-EPO as well as its long term effects on the
      premature infant.

PMID- 9035643
TI  - Touch during preterm infant resuscitation.
AB  - Preterm infants frequently require resuscitation in the delivery room. Under the
      intense circumstances of providing lifesaving interventions, caregivers may be
      unaware of the amount and kind of touch an infant receives. The purpose of this
      qualitative, ethologic study was to describe the kinds of touch that occur during
      resuscitation of premature infants immediately after delivery as viewed on
      videotape. The convenience sample consisted of ten videotapes of premature infant
      resuscitation performed at a tertiary care center. Using Spradley's Developmental
      Research Sequence, a description of kinds of touch--including mechanical and
      human touch--was developed. Descriptive research conceptualizing touch promotes
      awareness of current practice and may lead to alterations in clinical practice
      that best support the adaptive response in the depressed infant.

PMID- 9035642
TI  - Breastfeeding, dehydration, and shorter maternity stays.
AB  - Over a five-month period eight breastfed infants required readmission to Wesley
      Long Community Hospital in Greensboro, North Carolina, within 48 hours of
      discharge from the newborn nursery. The primary diagnoses upon readmission
      included hyperbilirubinemia and suspected sepsis. At discharge from the intensive
      care nursery, mild dehydration secondary to inadequate breastfeeding was deemed a
      significant factor in precipitating the need for readmission. This increase in
      readmissions represented a significant change from the past year. An intensive
      review of each initial hospital stay was conducted to attempt to identify
      causative factors and to develop a profile of infants who might be at risk for
      readmission in the future.

PMID- 9035644
TI  - Bedding twins/multiples together.

PMID- 9035645
TI  - Neonatal glucose screening.

PMID- 9035646
TI  - Ethical decisions: who should decide?

PMID- 9035647
TI  - Herpes simplex virus infection in the neonate: clinical presentation and
      management.
AB  - Herpes simplex virus (HSV) infections in the neonate can be acquired during
      pregnancy and during and following the birth process. The most common mode of
      transmission is from exposure to the virus in the birth canal at the time of
      delivery. HSV is among the less common infections in neonates. This often leads
      to delay in diagnosis and treatment, increasing the risk of a poor or fatal
      outcome. Clinically, HSV infection often presents in preterm or term infants with
      signs and symptoms similar to those of bacterial sepsis. Their immature immune
      systems puts preterm infants at higher risk for serious disease. A positive
      maternal history of HSV is not needed to support diagnosis; typically the mother
      is asymptomatic. Primary maternal infection usually leads to more serious disease
      in the neonate. It is important that caregivers recognize the subtle signs and
      symptoms of HSV infection so early diagnosis and prompt treatment can be
      instituted.

PMID- 9035649
TI  - On becoming an NICU.
AB  - Over the past 20 years, there has been a dramatic change in the way nursing care
      is delivered in this 52-bed community hospital NICU. In the early 1970s,
      technologic and medical innovations produced a significant improvement in infant
      survival. The nurse's role at that time was to deliver the various prescribed
      treatments and master the array of new gadgetry. This approach escalated until
      the mid 1980s, when it was recognized that something very important was missing
      from nursing practice. This realization began an internal process in a small
      group of nurses that eventually expanded to include the majority of staff. The
      process is outlined in the text, and the outward changes that resulted from the
      internal process are outlined in the tables.

PMID- 9035648
TI  - Inherited disorders: a genetic primer.
AB  - Identification of inherited or genetic disorders has important implications for
      the prognosis and treatment of affected infants. This article addresses the three
      most common categories of genetic disorders--single-gene defects, chromosomal
      abnormalities, and multifactorial conditions. The principles of transmission,
      risk of inheritance, and clinical significance of each category are discussed,
      with examples of inherited disorders in each category.

PMID- 9035650
TI  - Discordant twins: a case report.
AB  - Multiple gestations account for 10 to 12 percent of perinatal deaths. Of all
      intrauterine deaths in twins, 73 percent are associated with monochorionic
      placentation. Monochorionic twins have higher rates of perinatal mortality,
      birthweight discordancy, and intrauterine growth retardation than do dichorionic
      twins. Follow-up studies indicate that twins remain at a disadvantage for
      subsequent growth and intellectual achievement. The history and hospital course
      of a set of discordant twins is presented, describing the extensive morbidity and
      prolonged hospitalization.

PMID- 9035651
TI  - Facilitating early discharge from the NICU: the development of a home gavage
      program and neonatal outpatient clinic.

PMID- 9035652
TI  - A river runs through us.

PMID- 9035653
TI  - ECMO and pharmacotherapy.

PMID- 9035654
TI  - Neonates with congenital heart disease, Part II: Congenital cardiac defects with
      increased pulmonary blood flow.
AB  - Generally, cardiac lesions with increased pulmonary blood flow demonstrate
      cardiomegaly, increased pulmonary vascular markings, and pulmonary congestion on
      the chest x-ray. These findings occur as a result of the following: 1. A left-to
      right shunt or mixing lesion in which excess volume of blood flow causes dilation
      of cardiac chambers, resulting in the appearance of cardiomegaly, and in which
      increased pulmonary artery blood flow causes increased pulmonary vascular
      markings 2. Obstruction of blood flow that produces pulmonary venous hypertension
      and resultant pulmonary edema The next article in this series will address
      cardiac lesions with decreased pulmonary blood flow.

PMID- 9035655
TI  - Urokinase.

PMID- 9035656
TI  - Some implications of early auditory development for the environment of
      hospitalized preterm infants.

PMID- 9035657
TI  - The ballad of little Joe: a case study in experience.

PMID- 9035658
TI  - [Stenoses in the area of the inner nasal cavity (nasal valve stenoses)].

PMID- 9035659
TI  - [How traumatising is mechanical mucous membrane care after interventions on
      paranasal sinuses? A histological immunohistochemical study].
AB  - OBJECTIVE: Endonasal sinus surgery lead to more or less circumscribed mucosa
      defects exposing the underlying bone. Healing of these wounds is accompanied by
      crust formation, which may be subjected to mechanical debridement. It is not
      known whether this wound care impaires or facilitates wound healing. METHODS:
      Following sinus surgery, 72 crusts were removed from the operative site after
      having taken endoscopic photographs choosing different postoperative intervals.
      Mucosal biopsies were taken from beneath the crusts. All specimen were submitted
      to routine histological serial sections as well as immunohistochemical staining
      of epithelium. RESULTS: Local debridement of crusts avulsed parts of epithelium
      in 23% of cases during the first postoperative week. There was no histological
      evidence of avulsed epithelium with crusts removed the second week. This figure
      later increased to 16%. Possible trauma to regenerating mucosa cannot be
      predicted solely by the appearance of crusts. CONCLUSION: In principle, large
      crusts may disturb ventilation and drainage, causing secondary mucositis. Local
      care is mandatory in these cases. According to our examinations, mechanical
      debridement of wounds must respect the time-dependent irritability of the healing
      wound. There is little risk of impairing epithelization during the second week
      after surgery and the chance of sustaining the healing process is best.

PMID- 9035660
TI  - [Effect of postoperative endonasal mucous membrane care on nasal bacterial flora:
      prospective study of 2 irrigation methods with NaCl solution after paranasal
      sinus surgery].
AB  - BACKGROUND: Endonasal irrigation with saline solution is a widely used
      constituent of mucosal care after sinus surgery. This procedure could explain a
      repeatedly observed phenomenon: contamination of the endonasal mucosa by
      facultative skin pathogens from the palm during paranasal sinus irrigation.
      METHOD: For this reason the effect of nasal rinses with saline solution on the
      endonasal bacterial flora was investigated (use of so-called nasal douche
      [Siemens & Co., Bad Ems] compared to rinsing by hand). In 36 patients (23 m., 13
      f., 36 +/- 19.5 years of age) with chronic sinusitis, a total of 288 swabs was
      collected before, during, and after surgery. The collected specimens were
      transferred to a Port-A-Cul transport medium and processed within four hours.
      RESULTS: Two hundred sixty-six cultures of 325 bacterial strains were aerobic
      (82%), while 59 were anaerobic (18%). Staphylococcus aureus (33%) and
      representatives of the Enterobacteriaceae family (31%) were the most common
      enriched germs. The number of times that enterobacteriaceae could be isolated was
      significantly (p < 0.05) lower (13%) when a nasal douche was used than when
      irrigation was done using the palm (38%). An irrigation technique-related effect
      was found on neither the spectrum of the pathagonic organisms nor the wound
      healing process. CONCLUSION: The frequent isolation of enterobacteria in nasal
      swabs of individuals rinsing by hand constitutes the difference between
      irrigation by nasal douche and by hand in the postoperative care of the endonasal
      mucosa. These pathogens can sustain the paranasal sinus system.

PMID- 9035661
TI  - [Endogenously formed nitric oxide in nasal mucosa of the human: detection by
      nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry].
AB  - BACKGROUND: Nitric oxide (NO) is an intercellular transmitter, both in the
      central and in the peripheral nervous system. In addition to nerve cells, NO is
      also produced in epithelial cells of various tissues and in the endothelium. NO
      is formed by the action of nitric oxide synthase (NOS). There is evidence that
      NOS can be marked by NADPH-diaphorase (NADPH-d) activity in many cell types. The
      aim of this study was to identify NOS-positive structures in human nasal mucosa
      by using NADPH-d-histochemistry. METHODS: Frozen sections from inferior
      turbinates were fixed with buffered formalin and then treated according to the
      description of Vincent and Kimura. Additionally, the same sections underwent a
      double staining procedure for acetylcholinesterase (Karnovski-Roots) to show a
      correlation with cholinergic nerve structures. RESULTS: Strong reactions were
      found in the epithelium and in nerve fibres, compared to less NADPH-d activity in
      seromucous glands and the endothelium of the different vessel types. Singular
      NADPH-d positive nerves were found within nerve bundles, periarterially, in the
      subepithelial layer and surrounding glands and their ducts. A frequent
      localisation of NADPH-d could be detected in parasympathetic nerve fibres.
      CONCLUSIONS: The occurrence of NADPH-d in epithelial, glandular and nerval
      structures suggests that NOS takes part in physiological functions and possible
      pathophysiological processes of the nose. Similar to findings in various other
      organs this investigation demonstrated that the neurotransmitter NO can also be
      associated with the parasympathetic nervous system in the human nasal mucosa.

PMID- 9035662
TI  - [Structure and function of the ventral vocal cord insertion. From the clinical
      viewpoint].
AB  - BACKGROUND: Spread of cancer at the ventral vocal fold insertion zone has been
      discussed controversially until today. One reason for this is the so far
      insufficient knowledge of the anatomical structure and function of the insertion
      zone. METHODS: The present study analyses the structures of laryngeal anterior
      commissure by means of histological, immunohistochemical and electron
      microscopical methods. Investigations are performed on vocal cords of 17 male and
      13 female (aged 21-88 years) in three planes. RESULTS: The vocal ligament inserts
      at the anterior commissure via two characteristic structures: the noduli
      elastici, which consist of two different morphological zones, and the vocal
      ligament tendon, a dense mesh of connective tissue rich in sulfated
      glycosaminoglycans. In the lower part of noduli elastici collagen and elastic
      fibres form a meshwork around embedded cells; in the upper part fibres are
      running in parallel. The vocal ligament tendon is connected to the thyroidal
      cartilage or bone by fibrocartilage. This area lacks a perichondrium or
      periosteum. At the beginning of osteogenesis vessels of plica vocals penetrate
      the bony thyroidal skeleton and contact with extralaryngeal vessels. CONCLUSIONS:
      Connective tissue cells of the insertion zone and extracellular matrix components
      formed by these cells fulfil biomechanical functions by equalizing the different
      elastic moduli of tendon, cartilage or bone. Ventral spread of vocal fold
      carcinomas is made possible by the lack of periosteum in the insertion zone as
      well as ossification and associated vascularisation of the thyroid cartilage.

PMID- 9035663
TI  - [Use of MR-controlled laser-induced thermotherapy in recurrent squamous
      epithelial carcinoma of the head-neck area].
AB  - BACKGROUND: The management of patients with recurrent carcinomas of the head and
      neck that had been treated before by surgery, radiation, and/or chemotherapy
      presents a considerable problem. The value of the MR-controlled laser-induced
      thermotherapy (LITT) was analysed as a new palliative treatment modality. METHOD:
      LITT was used in five patients with recurrent head and neck squamous cell
      carcinomas, who had undergone established methods of treatment. One patient with
      a primary laryngeal carcinoma, who refused surgery, was treated by LITT in
      addition to radiation. A Nd:YAG laser was used to deliver laser light via an
      applicator directly into the tissue and to produce tumor necrosis. Using two
      special MR thermosequences (Thermo-TurboFLASH-, modified FLASH-2 D-Sequenfe) the
      laser process was controlled on line. The necroses were measured by a static and
      dynamic area calculation program based on a pixel evaluation. RESULTS: The
      induced tumor necroses ranged from 4 cm3 to 28 cm3. In all cases the MR
      thermosequences showed a loss of the signal up to 15 mm around the top of the
      applicator. In the post-interventional T1 sequences with intensified contrast,
      the coagulation necroses were represented as hypovascular areas. No side effects
      were seen and five of the patients felt an improvement of clinical symptoms.
      CONCLUSION: LITT as a minimal invasive, MR-controlled method may be a good
      alternative in palliative therapy of head and neck carcinomas.

PMID- 9035664
TI  - [Systematic analysis of cervical lymph node metastasis of larynx and hypopharynx
      carcinomas--a clinical computerized tomography study with special reference to
      extension of the primary tumor].
AB  - PURPOSE: To assess the incidence and patterns of cervical lymph node metastases
      in laryngeal and hypopharyngeal carcinomas according to the location, extension,
      and relation of the primary tumor to the parapharyngeal compartments and tissues
      arising from different embryological structures as branchial arches and somites.
      PATIENTS AND METHODS: The findings of clinical and CT examinations of 230
      patients with histological evidence of laryngeal and hypopharyngeal carcinoma (44
      T1-, 33 T2-, 41 T3-, 112 T4-carcinomas with lymph node involvement in 116 cases)
      were evaluated retrospectively. Local tumor spread and relation of the primary to
      the parapharyngeal compartments and to tissues arising from different
      embryological structures such as branchial arches and somites were analysed and
      related to cervical lymph node involvement. RESULTS: The pattern of cervical
      lymph node involvement depends upon location and extension of the primary tumor
      in the adjacent tissues of the larynx and hypopharynx. The density of the
      lymphatic vessels in these areas determines the likelihood of lymph node
      involvement. The frequency of NO cases in carcinomas strictly located in the
      vocal cord (n = 31) was 100%; in the glottic-supraglottic, supraglottic, and
      transglottic cancer (n = 106) 85%; in larynx-hypopharynx carcinomas (n = 54) 26%;
      in hypopharynx carcinomas (n = 12) 17%; and in larynx-hypo-oropharynx carcinomas
      (n = 46) 9%. Tumors in tissues arising from branchial arches 4, 5, and 6 are
      glottic-supraglottic, transglottic laryngeal, and laryngeal-hypopharyngeal
      carcinomas. Metastases of these tumors were frequently found in the jugular lymph
      node chains, particularly if the developed tissue of the "primitive glottis" was
      invaded by the primary. Upper jugular nodes ipsilateral to a supraglottic or
      hypopharyngeal primary were usually involved. The frequency of metastases in the
      jugular lymph node chains decreased in craniocaudal direction. If the tumor
      invaded the posterior wall of the hypopharynx or tissues.

PMID- 9035665
TI  - [Multiple biopsy in diagnosis of laryngeal carcinoma].
AB  - BACKGROUND: The fate of patients suffering from laryngeal carcinoma is influenced
      strongly by the stage of the tumor at the time of diagnosis. This factor is also
      critical for preservation of the organ. It may be impossible to diagnose the
      tumor with the first biopsy even though the clinical and macroscopic aspect
      suggests a malignancy. METHODS: In a retrospective study, we examined 468
      patients with laryngeal carcinoma who were treated at the departments of
      otorhinolaryngology at the University of Basel (B) (198 patients from 1983-1992)
      or in Giessen (G) (270 from 1990-1995). The number of biopsies necessary to
      confirm the diagnosis was analysed and the follow-up of the patients was
      evaluated. Thirty of 32 negative histologic samples were reexamined. RESULTS: Of
      468 patients, 32 (7%, 27 [B] 14%; and 5 [C] 2%) required two to six biopsies to
      confirm the clinically suspected diagnosis: Twenty patients (designated as Group
      1) were diagnosed within one to three months, and no patient showed a change of
      tumor stage within that time. Their first biopsies have to be considered as
      "nonrepresentative". Eight patients (Group 2) were diagnosed within four to 24
      months and four patients (Group 3) more than 24 months after the first biopsy.
      Final treatment and outcome in patients from Group 1 was unchanged by the time
      delay in diagnosing the tumor. Seven of eight patients in Group 2 experienced an
      obvious progression of their tumor during the diagnostic period, which led to
      laryngectomy in several cases. In four patients, diagnosis was confirmed more
      than two years after the first biopsy. These were special cases such as
      development of cancer out of a papillomatosis or chronic laryngitis. CONCLUSIONS:
      A time delay of three months in diagnosing cancer of the larynx does not have a
      significant influence on organ preservation and prognosis, even though especially
      in small tumors suspicion of cancer should lead to a new representative biopsy as
      fast as possible to preserve the larynx.

PMID- 9035666
TI  - [Metastases of germ cell tumors to the ENT area--a rare differential diagnosis of
      lymph node metastases in unknown primary tumor].
AB  - BACKGROUND: Germ cell tumors of the testis usually metastasize to retroperitoneal
      lymph nodes, lungs, and liver. Other lymphatic or organ metastases especially in
      the head and neck are rare. CASE REPORTS: The cases of two men, ages 21 and 35,
      are presented. In both cases, the histologic examination of cervical lymph node
      specimen lead to the correct tumor diagnosis of testicular cancer. Multimodal
      urooncologic therapy led to long-lasting complete remissions in both cases.
      CONCLUSIONS: In young men between 20 and 35 years of age with cervical metastases
      of tumors of unknown primary site, germ cell tumors must be suspected. Histologic
      findings of non-squamous epithelial metastases (seminoma, embryonal carcinoma,
      chorionic carcinoma, teratoma, yolk sack tumor, and their combined forms) with or
      without retroperitoneal, mediastinal, or lung metastases; elevated tumor markers
      (human-chorionic gonadotropin, alpha-feto-protein, placental alkaline
      phosphatase, lactate dehydrogenase); and palpable intratesticular mass lead to
      the correct tumor diagnosis. Early detection of the disease is essential for
      successful therapy and long-term remission.

PMID- 9035667
TI  - [Central (reparative) giant cell granuloma of the paranasal sinus].
AB  - BACKGROUND: The central giant-cell (reprative) granuloma is an uncommon bone
      lesion usually located in the mandible and maxilla. In contrast to giant cell
      tumors of the extra-craniofacial skeleton, the origin of this lesion is
      considered to be non-neoplastic, reactive, and triggered by trauma or
      inflammation. The tumor occurs mainly in young people; they complain of regional
      indolent swelling of the jaw eventually leading to loosening of the teeth. CASE
      REPORT: In the paper, the authors describe the unusual case of a central giant
      cell granuloma in a young male. Diagnostic procedures, adequate therapeutic
      approach, and an overview of differential diagnostic considerations are provided.
      RESULTS: The pedunculate tumor was removed surgically. In endoscopic controls no
      recurrent growth has been seen up to one year after removal. CONCLUSIONS: Even
      though the giant-cell reparative granuloma is rare, it may also occur in the
      nasal cavity. Diagnosis is established by histologic findings and the typical
      clinical appearance. Surgical removal is the treatment of choice.

PMID- 9035669
TI  - [Sterile cover for the microscope in ENT operations].
AB  - Complete sterile covering of operating microscopes for ENT operations has been
      achieved using sterilizable cases of stainless steel, which offer the following
      advantages: Quick and easy application to different types of microscopes.
      Considerable cost savings. Significant waste reduction.

PMID- 9035668
TI  - [Hypoglossal nerve paralysis after endonasal paranasal sinus operation in
      intubation narcosis].
AB  - BACKGROUND: In the literature the possibility of a pressure trauma to the
      hypoglossal nerve between the root of the tongue and the ligamentum stylohyoideum
      is discussed. A recent in vivo study examined the effects of forced reclination
      of the head on the nerve. PATIENT: A left sided hypoglossal nerve paralysis
      occurred in a patient after an endoscopically controlled endonasal operation
      under general anesthesia with transoral intubation. RESULTS: Clinically and
      electrophysiologically the palsy seemed to be transient due to neurapraxia. An X
      ray of the neck performed after the operation revealed a calcification of the
      left ligamentum stylohyoideum. All the other diagnostic studies (ultrasound of
      the neck, neurological examination, serological tests, and CT scan of the head)
      did not show any abnormalities. This is the first time, that a postoperative
      hypoglossal nerve palsy has been observed, which could not be explained by
      extensive stretching or pressure. CONCLUSION: We believe that the short pressure
      of the Mcintosh spatula produced the hypoglossal nerve palsy described.

PMID- 9035670
TI  - [Stenoses of the area of the internal nasal cavity (nasal valve stenosis)].

PMID- 9035671
TI  - [In situ sound pressure measurement in a professional violinist with bilateral
      tinnitus].
AB  - BACKGROUND: A case of a professional violinist suffering from a bilateral
      tinnitus is presented. The musician reported the tinnitus to be louder and more
      straining when playing his Vuillaume violin (France 1840) as compared with his
      Carcassi violin (Italy 1763). CASE REPORT: In the 42-year-old musician,
      audiometry revealed a normal hearing threshold in the right ear and a slight
      hearing loss in the left ear of up to 20 dB between 2 kHz and 8 kHz. Transitory
      evoked otoacoustic emissions could only be measured in the right ear. The
      tinnitus could be masked (distance type); residual inhibition was only seen in
      the right ear. By sound intensity measurements in both external auditory canals,
      the different sound spectra of both violins could be demonstrated. When playing
      with "forte" intensity, sound pressure reached peaks of over 90 dB. The tinnitus
      was ameliorated by lidocaine infusions. DISCUSSION AND CONCLUSIONS: The different
      sound spectra of both violins may be the reason for the enhancement of the
      musician's tinnitus. Interference of air and bone-conducted sound could lead to a
      cochlear overlap and thus influence the tinnitus although such a phenomenon can
      not be verified. It was previously reported that high-pitched instruments may
      cause tinnitus sensations in performing musicians. A review of the literature
      surprisingly reveals that although professional musicians are exposed to sound
      pressure levels that may cause hearing impairment, only very few do develop one.
      This fact has to be taken into account whenever an occupational disease is
      suspected.

PMID- 9035672
TI  - [Vertigo and anxiety disorders--results of interdisciplinary evaluation].
AB  - BACKGROUND: Vertigo is a common symptom that often remains unexplained despite
      extensive medical evaluation. Psychiatric and psychosomatic disorders are usually
      considered after all somatic causes of vertigo have been ruled out. METHODS:
      Eighty-three patients referred to neurological or psychosomatic outpatient
      treatment received an extensive neurootologic and psychosomatic evaluation: one
      (or two) diagnostic psychiatric psychodynamic exploration(s), a structured
      interview, psychometric tests (SCL-90-R, STAI-G X2 and GBB). The patients were
      divided into four diagnostic groups: psychic causes only (psychogenic group),
      neurootologic causes only (somatic group), both diagnoses (psychosomatic group),
      neither diagnosis (group IV). RESULTS: Twenty-three patients had organic vertigo,
      thirty-nine patients had psychogenic vertigo and in seventeen cases a vestibular
      lesion initiated the development of a neurotic disorder, particular anxiety
      disorder. Most of the patients of the psychogenic and psychosomatic group had
      anxiety or phobic disorders. The patients with psychogenic or psychosomatic
      symptoms of vertigo generally report a higher level of subjective distress; the
      periods of disability are significant longer. CONCLUSIONS: The study suggests
      that assessment of psychiatric and psychosomatic symptoms should always
      accompany, not follow, neurootologic evaluation of vertigo. An early
      interdisciplinary therapy should be started to prevent the chronicity of the
      symptomatology.

PMID- 9035673
TI  - [Nd:YAG laser light-induced reduction of the nasal turbinates].
AB  - BACKGROUND: Different types of laser have been used for reduction of hyperplastic
      inferior turbinates in the recent years with good results. Reports about the long
      term benefit of the laser treatment are rare. PATIENTS AND METHODS: At the Dept.
      of Otorhinolaryngology, Head and Neck Surgery, University of Kiel between 1987
      and 1994, 89 patients with hyperplastic inferior turbinates were treated using
      the Nd:YAG laser. With the Nd:YAG laser, low-dose irradiation (laser power
      density: 1770-3540 W/cm2, non-contact-technique) of the entire turbinate is
      performed under endoscopic control. RESULTS: Twenty-seven patients (67.5%) who
      were treated by laser surgery were without complaints 6 months postoperatively.
      After one and two years, this applied to 29 (72.5%) and 26 (65%) patients,
      respectively. The success of treatment was seen after several months. The
      procedure involves little or no bleeding. The mucocillary clearance of the
      epiturbinate is not disturbed by Nd:YAG laser treatment. CONCLUSIONS: The Nd:YAG
      laser is suitable for the treatment of hyperplastic inferior turbinates. The
      disadvantages of the Nd:YAG laser therapy are that the success of treatment
      becomes evident only after weeks or months due to the scarring process which
      takes very long, and time consuming wound care is necessary.

PMID- 9035674
TI  - [Treatment of postoperative "uncontrollable" nosebleed by embolization of the
      maxillary artery].
AB  - BACKGROUND: Embolization of the maxillary artery is a successful treatment,
      alternative in cases of recurrent severe nosebleeds when anterior and posterior
      nasal packing have failed to achieve permanent control. PATIENTS AND METHOD: Two
      cases of male patients are presented who suffered from severe nosebleeds after a
      submucous resection of the septum, electrocautery of the inferior turbinate, and
      submucosal conchotomy. Anterior and posterior nasal packing proved to be
      unsuccessful. Angiography of the internal and external carotid artery was
      performed and selective embolization of the mayillary artery with absorbable
      material followed. RESULTS: In both cases embolization was successful and
      uneventful. Twenty-four hours after treatment, the nasal packing was removed and
      no recurrence was observed. CONCLUSION: Selective embolization of the maxillary
      artery is a successful alternative for the treatment of severe recurrent
      nosebleeding-equally effective with surgical ligation of the bleeding arteries.

PMID- 9035675
TI  - [Use of high frequency cinematography in diagnosis of globus sensation].
AB  - BACKGROUND: Globus pharyngis is a frequent symptom in patients who consult an
      otolaryngologist. In many cases, routine diagnostic work-up including history,
      clinical examination, and barium swallow fail to revealing the underlying
      pathogenesis. PATIENTS AND METHOD: In a retrospective study, we present 51
      selected patients suffering from globus pharyngis of unknown origin who were
      investigated by high-speed cineradiography in a standardized manner. RESULTS:
      Twenty-four of the patients enrolled in the study (47.1%) showed functional
      and/or structural swallowing disorders. In 13 cases (25.5%) dyskinesias of the
      superior esophagus sphincter muscle were found. Five of these patients (9.8%)
      also had an inconstant hypopharyngeal diverticulum. Six cases (11.8%) showed
      laryngeal penetration or tracheal aspiration. In four cases (7.8%) functional
      disorders of pharyngeal, and in three cases (5.9%) functional disorders of oral
      bolus transport were found. Furthermore one hypopharyngeal web (1.9%) and two
      benign tumors (3.9%) were detected. In many cases, varying combinations of these
      findings occurred. CONCLUSION: Using high-speed cineradiography for evaluation of
      globus pharyngis results in an increased incidence of pathologic findings, and
      thus is an important method for interdisciplinary diagnostic work up of patients
      suffering from this symptom.

PMID- 9035676
TI  - [Soft tissue sarcomas of the ENT area. A report of experiences of the Vienna
      University ENT Clinic].
AB  - BACKGROUND: Soft-tissue sarcomas of the head and neck are rare. Local recurrence
      is common, and wide excision is thought to be the mainstay of treatment. Surgical
      radicality is limited by the vicinity of vital organs. Improvement of cure rates
      therefore is expected mainly from combined treatment modalities. METHOD:
      Retrospective analysis of 32 cases of soft-tissue sarcoma on file at the
      Department of Otorhinolaryngology of the University of Vienna between 1954 and
      1994. RESULTS: The most frequent descriptive histological diagnosis was
      polymorphic cell sarcoma in 11 cases. An immunohistological verification was
      possible in seven cases. The larynx and the pharynx (16 percent each) were the
      most common sites of affection. Incidence peaks were noted in the third and
      seventh decade of age. Treatment during the 1950s consisted of surgery and/or
      irradiation and was supplemented from the 1960s on by polychemotherapy. The
      median survival was 29 months. Three patients are alive, two patients died free
      of disease and six patients were lost to follow-up. CONCLUSION: Permanent cure
      was rare but each therapeutic regimen seemed to provide prolongation of life. The
      most important prognostic factors were tumor size, histologic grade, and surgical
      margins.

PMID- 9035677
TI  - [Expression of cellular antigen of hypopharyngeal carcinoma in different culture
      conditions].
AB  - BACKGROUND: The need to improve therapy regimes, determine prognosis, and study
      biological properties of tumors extracorporally led to development of different
      experimental systems. In order to approach the in vivo situation, specific
      properties of the tumors of origin should be retained by the cells in culture
      over relatively long periods. However, culture conditions may change expression
      of cellular antigens. METHODS: Cryosections of a hypopharyngeal carcinoma were
      compared in this respect with different cultivation systems (2-dimensional
      monolayers [ML], 3-dimensional multicellular tumor spheroids [MTS] and substrate
      cultures on Gelita) in regard to expression of cytokeratins (CK) 1, 7, 10, 14, 18
      and 19, vimentin, neurofilament (NF) kD200 and 68, ganglioside GD2, oncogene
      products (P53 mutant and wild), and membrane-associated antigens (HLA-ABC and 
      DR, epidermal growth factor receptor EGFR). RESULTS: Semiquantitative
      immunohistochemical methods revealed differences in expression of CK1, 14 and 19,
      GD2, and P53 mutant between these systems. CONCLUSION: Pronounced expression of
      markers in MTS compared to original biopsy and monolayer emphasizes the
      importance of cell-cell contact and 3-dimensionality or metabolic stress.
      However, weak marker expression within substrate cultures may reflect loose cell
      cell contact observed. In these experiments, the antigenic configuration of MTS
      resembled the one of the original tumor more than the other culture systems:
      monolayer and growth on substrate. As vimentin and NF are not expressed by
      healthy epithelial cells of adults, occurrence of intratumoral vimentin and NF
      could point to derepression of early differentiation antigens.

PMID- 9035678
TI  - [The SMAS (subcutaneous musculo-aponeurosis system) flap: a possibility for
      filling out soft tissue defects after parotidectomy].
AB  - BACKGROUND: Parotidectomies sometimes leave a conspicuous soft-tissue defect in
      the dorsal part of the cheek. METHODS: The authors present a modification of the
      standard technique of parotidectomy which is reserved for the surgical management
      of benign parotid tumors. The incision of the skin follows the guidelines for
      standard subcutaneous rhytidectomy with a modification according to the Redon
      incision. They use flaps of the subcutaneous musculoaponeurotic system (SMAS),
      which they fold or rotate in order to fill the soft-tissue defect following
      parotidectomy. The preparation of the skin and the SMAS in layers from the
      lateral to the medial aspect of the cheek does not affect the blood supply which
      comes from medially running vessels. RESULTS: Forty patients have been operated
      on using these modifications of the standard technique. A postoperative follow-up
      of more than one year could be controlled in 31 cases. Thirty patients showed an
      inconspicuous dorsal region of the cheek without a soft-tissue defect compared to
      the other side. They did not wish a secondary operation for an aesthetic
      improvement except two scar revisions. CONCLUSION: To date this surgical concept
      has proved its worth.

PMID- 9035679
TI  - [Primary cholesteatoma of the petrous bone apex].
AB  - BACKGROUND: Primary cholesteatoma of the temporal bone is a very rare disease.
      Initially, the tympanic membrane is intact, and often facial palsy may be the
      presenting symptom. The authors present a case of primary cholesteatoma which was
      surgically treated using a transmastoid-translabyrinthine approach. Other
      surgical approaches to the petrous apex are discussed.

PMID- 9035680
TI  - [Juvenile xanthogranuloma of the auricle].
AB  - BACKGROUND: Juvenile xanthogranulomas are rare benign tumors of histiocytic
      origin with cutaneous manifestation predominantly in the head and neck. A case of
      a 12-month-old girl is presented. CASE REPORT: A tumor of the inferior crus of
      the left auricle had been noticed three weeks after birth. It was of yellowish
      color, bosselated and firm, and not mobile. During operation the tumor seemed
      lipomatoid and affected both cutis and subcutis. Histologically cutaneous
      structures were regular. Subcutaneously, cell-rich connective tissue with foamy
      histiocytes and Touton giant cells were observed as characteristic features of a
      juvenile xanthogranuloma. DISCUSSION: The pathogenesis of this tumor is unclear.
      The definite diagnosis is established by histological examination. Histological
      differentiation should include malignant tumors of histiocytic origin
      (dermatofibro-sarcoma protuberans, histiocytoma, atypical fibrous histiocytoma,
      fibro-xanthosarcoma) and malignant melanoma. Surgery is the treatment of choice
      only in cases in which the clinical diagnosis is doubtful, since juvenile
      xanthogranulomas usually heal spontaneously.

PMID- 9035681
TI  - [Epithelioid sarcoma of the parotid region].
AB  - BACKGROUND: Epithelioid sarcoma has been described in 1970 by Enzinger as a
      separate tumor entity. It is a rare soft-tissue tumor mostly found in the distal
      extremities in young adults. The head and neck region is only very infrequently
      affected. PATIENT AND RESULT: We report the rare case of a manifestation of an
      epithelioid sarcoma in the area of the right parotid gland in a 72-year-old
      patient. Only two more cases with a similar tumor entity and location have been
      described in the international literature. The patient underwent total
      parotidectomy, radical neck dissection, and postoperative radiotherapy two years
      ago and has been free of recurrence since then. CONCLUSIONS: Epithelioid sarcomas
      of the head and neck are very rare tumors. They are treated by radical local
      tumor removal, neck dissection, and postoperative radiotherapy. Prolonged
      postoperative follow-up is necessary since recurrences can occur after up to more
      than 15 years.

PMID- 9035682
TI  - Peptide hormone evolution: functional heterogeneity within GnRH and CRF families.
AB  - Recent investigations indicate that the gonadotropin-releasing hormone (GnRH) and
      corticotropin-releasing factor (CRF) family of peptides are each composed of at
      least two functionally discrete paralogous lineages. [His5Trp7Tyr8]GnRH (chicken
      GnRH-II) is associated with brain neuromodulatory and possibly peripheral
      endocrine activity, whereas [Arg8]GnRH (mammal GnRH) and its orthologues play
      major roles as hypothalamic releasing factors. Similarly, CRF appears to be the
      primary vertebrate ACTH-releasing peptide, whereas the paralogous lineage of
      urotensin-I-sauvagine has been associated with a variety of diverse peripheral
      activities. In phylogenetically older species, representatives of both GnRH and
      CRF family lineages have been characterized. Structural and functional
      conservation of these peptide systems in vertebrates suggest that additional GnRH
      like and CRF-like peptides will be found in the mammal brain.

PMID- 9035683
TI  - Multiple pathways for denaturation of horse plasma gelsolin.
AB  - Gelsolin purified from horse plasma carries a surface charge distribution that
      greatly influences how the protein unfolds, aggregates, or precipitates as a
      function of temperature or concentration of chemical denaturant. Modification of
      gelsolin with fluorescein isothiocyanate replaces positive charges on amine
      groups with bulky, negatively charged fluorescein moieties. This postpones
      thermally induced precipitation by about 10 degrees C [Koepf, E.K., and Burtnick,
      L.D. 1993. Eur. J. Biochem. 212: 713-718]. Interaction with cations such as Ca2+
      or guanidinium+ also alters the surface charge on gelsolin. This affects the
      structure of the protein in solution, modifies the pathway for unfolding, and
      moderates the onset of precipitation induced by chemical denaturants or heat.
      Denaturation of gelsolin is not interpretable in terms of a simple two-state
      cooperative mechanism. The pathway to a denatured state and intermediate
      structures present along the way depend upon the agent used to unfold the
      protein.

PMID- 9035684
TI  - Purification, characterization, and partial amino acid sequencing of an amphibian
      liver fatty acid binding protein.
AB  - The fatty acid binding protein (FABP) from toad liver cytosol was purified to
      homogeneity by a procedure involving gel filtration and anion exchange
      chromatography. The protein presented a molecular mass of 13 987 +/- 2 daltons
      determined by electrospray mass spectrometry. Native isoelectric focusing of the
      purified liver FABP revealed a single pI 6.8 band. On the other hand, the toad
      heart FABP showed a different mobility than that of toad liver FABP by both
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric
      focusing. Moreover, toad liver FABP cross-reacted with antisera to mammalian
      liver FABP but not with antisera to heart FABP. The difference between toad liver
      and heart FABPs was further confirmed by partial amino acid sequencing. As the N
      terminus of toad liver FABP was blocked, the protein was chemically and
      enzymatically cleaved and the resulting peptides were subjected to automated
      Edman degradation. Partial amino acid sequencing showed that the toad liver FABP
      is related to that of mammalian liver and is clearly different from the amphibian
      heart FABP as well as from the amphibian intestine FABP.

PMID- 9035685
TI  - pH and temperature dependence of the rate of compound I formation from the
      reaction of prostaglandin endoperoxide synthase with hydrogen peroxide.
AB  - The formation of primary oxidized compound of prostaglandin endoperoxide
      synthase, compound I, was studied as a function of pH and temperature using
      hydrogen peroxide as a substrate. Analysis of the results indicates that compound
      I formation is influenced by an ionizable group with a pKa of 4.06 +/- 0.04. The
      protonated form of hydrogen peroxide preferentially reacts with the unprotonated
      form of the enzyme over the pH range of 3.5 to 9.1, suggesting the importance of
      acid-base catalysis for compound I formation. The second-order rate constant for
      the reaction of the enzyme with hydrogen peroxide in the pH-independent region is
      (4.6 +/- 0.2) x 10(5) M-1 S-1 at an ionic strength of 0.1 M and temperature of
      4.0 +/- 0.2 degrees C. The effect of temperature on the rate of compound I
      formation was studied from 3.4 to 24.1 degrees C in the pH-independent region (pH
      6.98) and at a constant ionic strength of 0.1 M. The kinetic parameters obtained
      from the temperature dependence are the following: Arrhenius activation energy,
      Ea = 102 +/- 5 kJ/mol; free energy of activation, delta G++, 36 +/- 3 kJ/mol;
      enthalpy of activation, delta H++, 100 +/- 5 kJ/mol; entropy of activation, delta
      S++, 215 +/- 9 J/mol K. These activation values are very different from those
      obtained for the reactions of other peroxidases and catalases with hydrogen
      peroxide, indicating profound differences in active site structure.

PMID- 9035686
TI  - In vitro expression of a mouse tissue specific glutathione-peroxidase-like
      protein lacking the selenocysteine can protect stably transfected mammalian cells
      against oxidative damage.
AB  - The complete sequence of the mouse epididymal protein (MEP24) was cloned. It
      contains a 663 bp open-reading frame that, after conceptual translation, shows
      extensive identity with proteins belonging to the glutathione peroxidase (GPX)
      family. However, a major difference between GPX5 (MEP24) and other known GPXs
      concerns a protein domain known to be critical for GPX function. To find out what
      could be the physiological function of such a protein in the mouse epididymis, we
      have used a mammalian expression system to overexpress the GPX5 protein. Cells
      constitutively expressing the GPX5 protein were generated and assayed for their
      ability to metabolize regular substrates of GPX enzymes. Data presented here show
      that the GPX5-expressing cells can metabolize hydrogen peroxide in a manner that
      is consistent with a peroxidase activity. However, the substrate preference of
      the GPX5-expressing cells and their apparent insensitivity to a regular inhibitor
      of GPX enzymes suggest that the GPX5 protein belongs to a particular class of GPX
      proteins. Involvement of this protein in the physiology of the mouse epididymis
      is discussed.

PMID- 9035687
TI  - Constitutive expression of the E2F1 transcription factor in fibroblasts alters G0
      and S phase transit following serum stimulation.
AB  - The E2F1 transcription factor was constitutively expressed in NIH3T3 fibroblasts
      to determine its effect on the cell cycle. These E2F1 cell lines were not tightly
      synchronized in G0 phase of the cell cycle following serum starvation, as are
      normal fibroblasts. Instead, the cells are spread throughout G0 and G1 phase with
      a portion of the population initiating DNA synthesis. Upon serum stimulation, the
      remaining cells in G0/G1 begin to enter S phase immediately but with a reduced
      rate. Constitutive expression of E2F1 appears to primarily affect the G0 phase,
      since transit of proliferating E2F1 cell lines through G1 phase is the same as
      control cells. Consistent with a shortened G0 phase, the E2F1 cell lines have a
      significantly reduced cellular volume. Additionally, the first S phase after
      serum stimulation, but not subsequent S phases, is nearly doubled in the E2F1
      cell lines compared with control cells. Cell lines expressing a deletion mutant
      of E2F1 (termed E2F1d87), known to significantly affect cell shape, have cell
      cycle and volume characteristics similar to the E2F1 expressing cells. However,
      all S phase durations are considerably lengthened and the cells demonstrate
      delayed growth after plating.

PMID- 9035688
TI  - Disruption of the NAD(+)-specific glutamate dehydrogenase gene of Neurospora
      crassa by means of the RIP (repeat-induced point mutations) process.
AB  - The structural gene for the catabolite-repressed, substrate-induced NAD(+)
      specific glutamate dehydrogenase (gdh-1) of Neurospora crassa was disrupted using
      the process of repeat-induced point mutation (RIP). Plasmids containing
      incomplete copies of the gene, along with selectable markers, were introduced
      into germinated conidia by electroporation. The sexual progeny of a transformant
      containing an ectopically integrated copy of a plasmid, harbouring the 5'
      flanking region and a part of the coding sequence of gdh-1 DNA, was examined for
      the occurrence of RIP by (i) Southern blot analysis of the genomic DNA digested
      with the isoschizomers MboI and Sau3A, (ii) Northern blot analysis of total RNA
      in cultures subjected to repression and induction conditions for NAD-GDH, (iii)
      direct assessment of enzymatic activity, and (iv) evaluation of protein levels by
      Western blot analysis using a polyclonal anti-GDH IgG preparation. Attempts were
      made at delineating different regions of the gene exhibiting RIP by using 32P
      labelled DNA probes, corresponding to (i) the complete gene, (ii) a fragment
      containing the 5' flanking region plus two-thirds of the coding sequence, and
      (iii) the 5' flanking segment alone. The extent and relative location of RIP, as
      revealed by these hybridization probes, appeared to correlate with changes in
      specific activity under repression and derepression conditions. Mutant progeny,
      thus recovered, included isolates with altered regulatory features, such as
      constitutive expression, inability to elicit derepression, higher-than-wildtype
      GDH levels under derepression and inefficient repression.

PMID- 9035689
TI  - Repeat-induced point mutations of HSP80 gene of Neurospora crassa: methylation of
      duplicated DNA sequences in the vegetative state.
AB  - The process of repeat-induced point mutations (RIP) was used to disrupt the gene
      encoding the 80-kDa heat-inducible protein of Neurospora crassa. Germinated
      conidia of the wild-type recipient strain were electrotransformed with a plasmid
      containing a 7-kb fragment harbouring the complete hsp80 gene sequence. Some of
      the transformants with a duplication of hsp80 gene sequence showed extensive
      methylation of these sequences even in vegetatively growing cells. The presence
      of an extra gene copy in transformants of this type resulted in a marked
      reduction in the expression of this gene. Progeny of a cross of one such
      transformant, showing methylation of hsp80, was analyzed by Southern blot and
      Northern blot hybridization to examine the relationship between methylation and
      the accumulation of hsp80 mRNA under hyperthermia. In addition, HSP80 polypeptide
      levels were monitored in stressed and unstressed cells by immunoblot analysis
      using polyclonal anti-HSP80 IgG preparations. A correlation between the extent of
      RIP and expression of this gene was observed in the progeny isolates.

PMID- 9035690
TI  - Identification of protein kinase C isoenzymes in smooth muscle: partial
      purification and characterization of chicken gizzard PKC zeta.
AB  - The pattern of expression of protein kinase C (PKC) isoenzymes was examined in
      chicken gizzard smooth muscle using isoenzyme-specific antibodies: alpha, delta,
      epsilon, eta, and zeta isoenzymes were detected. PKC alpha associated with the
      particulate fraction in the presence of Ca2+ and was extracted by divalent cation
      chelators. PKC delta required detergent treatment for extraction from the EDTA
      EGTA-washed particulate fraction. PKC epsilon, eta, and zeta were recovered in
      the cytosolic fraction prepared in the presence of Ca2+. PKC zeta, which has been
      implicated in the regulation of gene expression in smooth muscle, was partially
      purified from chicken gizzard. Two peaks of PKC zeta-immunoreactive protein (M(r)
      76 000) were eluted from the final column; only the second peak exhibited kinase
      activity. The specific activity of PKC zeta with peptide epsilon (a synthetic
      peptide based on the pseudosubstrate domain of PKC epsilon) as substrate was 2.1
      mumol P(i).min-1.(mg PKC zeta)-1 and, with peptide zeta as substrate, was 1.2
      mumol P(i).min-1.(mg PKC zeta)-1. Activity in each case was independent of Ca2+,
      phospholipid, and diacylglycerol. Lysine-rich histone III-S was a poor substrate
      for PKC zeta (specific activity, 0.1-0.3 mumol P(i).min-1.mg-1). Two proteins,
      calponin and caldesmon, which have been implicated in the regulation of smooth
      muscle contraction and are phosphorylated by cPKC (a mixture of alpha, beta, and
      gamma isoenzymes), were also poor substrates of PKC zeta (specific activities,
      0.04 and 0.02 mumol P(i).min-1.mg-1, respectively). Chicken gizzard PKC zeta was
      insensitive to the PKC activator phorbol 12,13-dibutyrate or the PKC inhibitor
      chelerythrine. The properties of PKC zeta are, therefore, quite distinct from
      those of other well-characterized PKC isoenzymes.

PMID- 9035691
TI  - Purification and characterization of the double-stranded DNA-activated protein
      kinase, DNA-PK, from human placenta.
AB  - The double-stranded DNA-activated protein kinase (DNA-PK) is a serine-threonine
      protein kinase that is composed of a large catalytic subunit (p350) and a DNA
      binding protein of 70 and 80 kDa subunits known as the Ku autoantigen. When
      targeted to DNA by free DNA ends, DNA-PK phosphorylates many DNA-binding proteins
      and transcription factors. Previously, DNA-PK had only been purified and
      characterized from transformed human tissue culture cells. Here we report that
      DNA-PK is an abundant protein in human placenta and lymphocytes. We have purified
      the placental DNA-PK to homogeneity and show that its biochemical properties are
      similar to those of the HeLa cell enzyme.

PMID- 9035693
TI  - Early steps in the biosynthesis of MUC2 epithelial mucin in colon cancer cells.
AB  - Expression of the MUC2 mucin has been demonstrated in normal gastrointestinal and
      respiratory epithelium and in carcinomas of the gastrointestinal and respiratory
      tracts, breast, ovary, and bladder using RNA probes and (or) monoclonal
      antibodies reactive with peptide epitopes on the 23 amino acid tandem repeat.
      Mouse monoclonal antibodies 4F1 and 3A2 were previously obtained by immunization
      with mucin derived from the LS174T colon cancer cell line and a KLH conjugate of
      a synthetic MUC2 VNTR peptide. These antibodies react with distinct epitopes on
      synthetic VNTR peptides and with normal and malignant epithelial tissues. In the
      present study, we examined the biosynthesis of MUC2 in LS174T colon cancer cells,
      using these antibodies to immunoprecipitate labelled mucin. A very high molecular
      mass protein was immunoprecipitated following 1 min pulse labelling with
      [3H]threonine and [3H]proline. A slight increase in molecular mass was observed
      over the next 16 min; however, unlike the MUC1 mucin, there was no large
      difference in apparent molecular mass between the MUC2 protein precursor and
      fully processed mucin using separation by SDS-PAGE. O-Glycosylation began within
      1 h of synthesis of the protein core. Mucin secretion into the culture medium was
      detected in the 2nd hour following synthesis and was largely completed within 4 h
      of synthesis. Secreted mucin was far less reactive with these monoclonal
      antibodies than the precursor protein.

PMID- 9035692
TI  - Radiation inactivation and in situ renaturation of protein tyrosine kinases
      reveal a major 50-kDa enzyme as part of a membrane complex present in dividing
      but not in resting prostatic epithelial cells.
AB  - Because protein tyrosine kinases play a crucial role in the regulation of cell
      division and carcinogenesis, we have herein measured such enzyme activities
      (specific activity and subcellular distribution) and compared their
      characteristics with respect to hydrodynamic properties and radiation
      inactivation sizes as well as renaturation after electrophoresis in denaturing
      conditions in canine prostatic epithelial cells either in a resting (freshly
      isolated) or in a dividing (cultured cells) state. In quiescent cells, most
      protein tyrosine kinase activity was expressed by soluble proteins with a Stokes'
      radius (Rs) of 3.05 nm, a sedimentation coefficient (S20,w) of 4.0 S, and a
      molecular mass of 50 kDa. By contrast, in dividing cells (three days in primary
      culture), the specific activity was higher and the enzyme was mainly membrane
      bound. The use of a detergent (Triton X-100) allowed the extraction of most of
      that enzyme; its partial specific volume, S20,w and Rs were then 0.883 cm3/g, 4.0
      S, and 5.6 nm, respectively, hence yielding a molecular mass of 215 kDa, which
      decreased to 125-145 kDa when corrected for detergent binding. Probing these
      chromatography-peak fractions, 50 kDa from cytosol of resting cells and 215 kDa
      from membrane extracts of dividing cells, with a phosphotyrosine antibody
      following their incubation with ATP and electrophoresis in denaturing conditions
      revealed the presence of a common 50-kDa phosphotyrosylated protein along with
      three other bands (130, 75, and 40 kDa) in the high-Mr peak of enzyme. However,
      the radiation inactivation size for protein tyrosine kinases expressed in both
      resting and dividing cells were similar, 47.2 +/- 8.7 and 44.5 +/- 6.1 kDa,
      respectively. Furthermore, by renaturation after electrophoresis in denaturing
      conditions, major protein tyrosine kinase polypeptides of 50 kDa were identified
      in both cell populations. Taken together, these results indicate that, in
      dividing prostatic epithelial cells, membrane-bound protein tyrosine kinases of
      low molecular weight with properties similar to those of monomeric soluble forms
      present in quiescent cells are part of high-molecular weight complexes. This
      activation process may be critical for hormone-independent proliferation of
      prostatic epithelial cells.

PMID- 9035694
TI  - Characterization, chromosomal mapping, and expression of different ubiquitin
      fusion protein genes in tissues from control and heat-shocked maize seedlings.
AB  - Organisms possess at least two multigene families of ubiquitins: the
      polyubiquitins, with few to several repeat units, which encode a ubiquitin
      monomer, and the ubiquitin fusion (or extension) protein genes, which encode a
      single ubiquitin monomer and a specific protein. This report provides details
      about two ubiquitin fusion protein genes in maize referred to as MubG7 (uwo 1)
      and MubG10 (uwo 2). Each has one nearly identical ubiquitin coding unit fused
      without an intervening nucleotide to an unrelated, 237-nucleotide sequence that
      encodes for a 79 amino acid protein. The derived amino acid sequences of the two
      fusion proteins show that they differ by five amino acids (substitution by either
      a serine or threonine). MubG7 maps to chromosome 8L162 and MubG10 maps to
      chromosome 1L131. Analyses of the role(s) of these genes in response to heat
      shock (1 h at 42.5 degrees C) reveal that the level of these fusion protein mRNAs
      in the radicles or plumules from 2-day-old seedlings does not change; however,
      heat shock does cause a marked reduction in the accumulation of these same gene
      specific mRNAs in the radicles and plumules of 5-day-old seedlings. These data
      confirm the suggestion from our earlier work that there is precise modulation, in
      a gene-specific manner, of the response to developmental as well as environmental
      signals.

PMID- 9035695
TI  - A polysaccharide-peptide complex from cultured mycelia of the mushroom Tricholoma
      mongolicum with immunoenhancing and antitumor activities.
AB  - A polysaccharide-peptide complex with immunoenhancing and antitumor activities
      was obtained from the mycelial culture of Tricholoma mongolicum, an edible
      mushroom found in Northern China. The polysaccharide-peptide complex had a
      molecular mass of 15.5 kDa, as estimated by gel filtration, and a carbohydrate
      protein ratio of about 8:1 and was not adsorbed on DEAE-Sepharose CL-6B. It
      possessed the activities of activating macrophages, stimulating macrophage
      antigen-presenting activity, which in turn enhanced proliferation of T-cells, and
      inhibiting the growth of sarcoma 180 cells that had been implanted in mice.

PMID- 9035696
TI  - The cell biologist and the World Wide Web. World Wide Web sites.

PMID- 9035698
TI  - Cytoskeleton. Bibliography current world literature.

PMID- 9035697
TI  - Web alert. Cytoskeleton.

PMID- 9035699
TI  - Assessment of fetal pulmonic stenosis by ultrasonography.
AB  - This study was designed to determine (1) the value of Doppler echocardiography in
      depicting the presence of a fetal pulmonary stenosis, (2) its reliability in the
      assessment of the severity of the lesion, and (3) the usefulness of additional
      markers from the left side of the heart as criteria of severity. Fourteen
      pregnant ewes were included in this study (gestational age, 90 to 120 days).
      Banding of the fetal main pulmonary artery created mild (n = 3), moderate (n =
      3), and severe (n = 5) stenosis. Three lambs were sham operated. Intrauterine
      fetal Doppler echocardiographic data obtained 15 days after surgery were compared
      with preoperative values. Peak velocities recorded through the band increased
      linearly from baseline in the groups with mild and moderate stenosis but did not
      show any further increase in the group with severe stenosis. Compared with the
      sham-operated group, right ventricular output in the group with stenosis was
      either similar or reduced significantly. The increase in right ventricular free
      wall thickness was significantly greater in the groups with stenosis compared
      with that of the sham-operated group; the correlation with the degree of severity
      was r = 0.65 and p < 0.05. A A stronger positive correlation was found between
      the severity of stenosis and aortic valve diameters: r = 0.82 and p < 0.01. The
      strongest correlation was found for right ventricular/left ventricular outputs (r
      = 0.92; p < 0.001). Thus Doppler peak velocities through the obstruction can help
      detect pulmonic stenosis but are not reliable for the assessment of its severity
      during fetal life. Other ultrasound measurements such as the size of the aortic
      anulus and especially the ratio of right ventricular/left ventricular output
      could be used as sensitive markers of the severity of stenosis.

PMID- 9035700
TI  - Aetiology and pathogenesis of psoriasis.
AB  - The hereditary transmission of psoriasis is suggested by epidemiological data and
      familial association, but remains incompletely defined, not appearing to follow
      simple autosomal dominant or recessive patterns. The confusion may be due to a
      multifactorial inheritance, or to inheritance of only a 'predisposition' to
      disease which requires an environmental stimuli for expression. Recent advances
      in genetic mapping indicate genetic heterogeneity, and suggest that definition of
      psoriasis at the level of the gene may soon be possible. Two of the three major
      pathogenic features of psoriasis--abnormal keratinocyte differentiation and
      hyperproliferation of keratinocytes--are secondary to altered growth and
      maturation kinetics related to the normal wound healing process. The third major
      pathogenic feature--infiltration of inflammatory components into the skin--can be
      explained by keratinocyte release of a wide variety of cytokines, immune and
      inflammatory modulators. Three theories have been proposed for the relationship
      between epidermal keratinocyte and immunocyte activation. The first theory
      proposes direct activation of epidermal keratinocytes by physical, chemical, or
      ultraviolet injury, increasing the synthesis and release of cytokines, which
      trigger T-lymphocyte activation in an antigen-independent fashion. The other two
      theories propose persistent T-lymphocyte stimulation as a result of either
      antigen/superantigen presentation by antigen-presenting cells, or as a result of
      autoreactivity. One or more of these mechanisms may be operative in different
      patients, at different times, or in response to different environmental stimuli.
      Also, the genetic heterogeneity of psoriasis suggests that different mechanisms
      could be linked to different genetic loci. Advances in understanding the
      aetiology and pathogenesis of psoriasis suggest the possibility of innovative,
      targeted therapies.

PMID- 9035701
TI  - Tazarotene--first of a new generation of receptor-selective retinoids.
AB  - Tazarotene is a topically applied retinoid that targets the skin, the site of the
      fundamental defect(s) in psoriasis, modulating the major causes of the disease
      and achieving sustained efficacy. In vitro, binding of tazarotenic acid has been
      demonstrated to retinoic acid receptors (RARs), the probable molecular target of
      retinoid action in adult human skin, but not to retinoid X receptors (RXRs). In
      gene activation assays, tazarotene is selective for the RAR beta and RAR gamma
      subtypes. This selectivity could theoretically limit undesirable effects at the
      receptor level. In vitro, animal and clinical evidence reveals that topical
      tazarotene modulates all three pathogenic factors in psoriasis: abnormal
      keratinocyte differentiation, hyperproliferation, and increased expression of
      inflammatory markers. Tazarotene is minimally absorbed systemically after topical
      administration. Tazarotene is rapidly metabolized by esterase metabolism to its
      active free-acid form, tazarotenic acid, which has a relatively short elimination
      half-life (1-2 h). The pharmacokinetic profile of tazarotenic acid is
      predictable, with no significant accumulation. In preclinical toxicity studies,
      high topical doses produced only reversible topical irritation, and lower doses
      were well tolerated. Topical doses were neither carcinogenic nor teratogenic, had
      no effect on fertility or general reproduction, and were not phototoxic,
      sensitizing, or photoallergenic. The pharmacological selectivity of tazarotene
      and limited systemic exposure result in minimal systemic effects, while the
      lesser cytotoxic effects (relative to other retinoids) result in reduced local
      effects.

PMID- 9035702
TI  - Early clinical development of tazarotene.
AB  - Initial clinical investigations on tazarotene, a new acetylenic retinoid, have
      suggested potential usefulness in the treatment of mild-to-moderate plaque
      psoriasis. Tazarotene promotes healing of psoriatic lesions by modulating the key
      pathogenetic factors in this disease. It is not sensitizing, phototoxic, or
      photoallergenic, but causes moderate dose-related skin irritation. Systemic
      absorption is minimal and elimination is rapid, providing a low potential for
      systemic adverse effects. Tazarotene effectively treats mild-to-moderate plaque
      type psoriasis, the benefits seem to be sustained after the cessation of therapy,
      and once-daily treatment is equally effective as more frequent application.

PMID- 9035703
TI  - Safety, efficacy and duration of therapeutic effect of tazarotene used in the
      treatment of plaque psoriasis.
AB  - Topical therapies are first-line treatment for mild/limited stable plaque
      psoriasis. Disadvantages of currently available therapies include lack of short
      term efficacy and long-term maintenance, adverse effects, and cosmetic problems.
      Tazarotene is a new topical retinoid which has proven to be efficacious in the
      treatment of mild-to-moderate plaque psoriasis. Results from a large,
      multicentre, pivotal study show that a once-daily application is as effective as
      a first-line monotherapy, providing rapid resolution of signs and symptoms and
      sustained therapeutic effects in some patients. Tazarotene gel is cosmetically
      acceptable, and is minimally absorbed systemically, with adverse events limited
      to local irritation.

PMID- 9035704
TI  - Oral retinoids--efficacy and toxicity in psoriasis.
AB  - Psoriasis is a disease of unknown aetiology, affecting approximately 1-3% of the
      population. In most cases involving relatively localized disease, patients are
      best managed with either topical therapy alone or topical therapy in combination
      with UV-phototherapy. However, approximately 35% of patients do not respond well
      to these conventional treatments or have moderate-to-severe disease requiring
      more aggressive forms of therapy. The second-generation retinoids, etretinate and
      its metabolite acitretin, are important additions to the armamentarium of agents
      used to treat these recalcitrant or severe forms of the disease. Generalized
      pustular psoriasis generally responds well to high-dose (0.7-1 mg/kg/day) oral
      retinoid monotherapy. In contrast, increasing small doses of the retinoid are
      recommended initially in erythrodermic psoriasis in order not to provoke the
      disease. Long-term clinical experience favours a combination treatment of the
      retinoid with either topical and/or UV irradiation in chronic plaque-like
      psoriasis. Both oral retinoids have comparable efficacy and tolerability
      profiles, and the relapse rates for both drugs are similar. The toxicities
      associated with both short- and long-term treatment with oral retinoids are
      significant and include mucocutaneous effects, adverse modulation of serum lipid
      chemistries, elevation of liver enzymes, and after long-term chronic dosing,
      skeletal and ligamentous calcification, and hyperostosis. Both etretinate and
      acitretin, like all retinoids, are known teratogens in animal models, and
      documented evidence exists for teratogenic activity in humans as well.
      Consequently, women of childbearing age are strongly advised to avoid pregnancy
      during treatment and up to 5 years following cessation of therapy with both
      etretinate and the carboxylic acid metabolite acitretin.

PMID- 9035705
TI  - [Aspergillosis and AIDS].

PMID- 9035706
TI  - [Pseudomonas spp. infections in patients with HIV infections].
AB  - BACKGROUND: The aim of this study was to describe the characteristics of the
      infections by Pseudomonas spp. observed in patients with HIV infection in Spain.
      METHODS: A retrospective study was performed of the isolations of Pseudomonas
      spp. in microbiologic samples of patients with HIV infection in three hospitals
      from Mallorca, Spain, since 1986. RESULTS: Twenty-nine patients with some
      positive culture for Pseudomonas were reviewed. In 20 cases the infection
      presented in advanced stages of the disease when the patient fulfilled AIDS
      criteria. The most frequent foci in both community acquired and nosocomial
      infection was respiratory (16 and 3 cases, respectively). Fifty percent of the
      cases presented bacteremia. The classically described predisposing factors for
      infection by this germ were presented in 19 patients. Pseudomonas aeruginosa was
      the most frequently isolated type (22 cases). Only 5 patients received the
      appropriate treatment on admission. Clinical cure was achieved in 23 patients,
      with recurrence being observed in 10. Five patients died in relation to the
      infection. CONCLUSIONS: Infections by Pseudomonas spp. in Spain appear to have
      increased in frequency in patients with HIV infection in the last decade. These
      infections appear in advanced phases of the disease and mainly involve the lung,
      with high rates of bacteremia and a high number of recurrence. Empiric treatment
      of patients with advanced HIV infection with suspicion of bacterial infection
      should include antipseudomonic drugs.

PMID- 9035707
TI  - [Bactericide activity of sulbactam before bacteria belonging to the Acinetobacter
      calcoaceticus-Acinetobacter baumannii complex].
AB  - BACKGROUND: To evaluate the bactericidal activity of colistin, imipenem and
      sulbactam against 24 Acinetobacter calcoaceticus-Acinetobacter baumannii complex
      isolations. METHODS: Bactericidal activity was estimated by using killing curves
      method. The concentrations employed were: colistin 4 mg/l, imipenem 8 mg/l and
      sulbactam 8 and 32 mg/l. RESULTS: Colistin was bactericidal in 24 isolations
      after 6 hours of incubation. When we used 8 mg/l of imipenem we detected
      bactericidal activity at the susceptible strains (MIC < or = 4 mg/l). We found
      bactericidal effect in 15 of 18 strains susceptible to sulbactam when we used 8
      mg/l in killing curves after 24 hours of incubation. Using 32 mg/l we detected
      the same effect in 18 strains with MIC < or = 8 mg/l. CONCLUSIONS: Considering
      the high incidence of resistance in Acinetobacter spp. to several antibiotics
      including imipenem, we consider that sulbactam could be an excellent therapeutic
      alternative because it presents bactericidal activity in susceptible strains.

PMID- 9035708
TI  - [Antibiotic resistance in Salmonella enterica: an increasing problem].
AB  - OBJECTIVE: To determine the evolution of the frequencies of Salmonella enterica
      serotypes and their resistance to antimicrobial agents. METHOD: A retrospective
      study of all S. enterica strains isolated from stool samples in the Hospital
      Clinico Universitario of Zaragoza over the period 1990-1994. RESULTS: Enteritidis
      was the most frequently isolated serotype (62.9%), although it showed a
      progressive decrease (from 76.2% in 1990 to 39.8% in 1994). Typhimurium was the
      serotype showing the highest resistance levels, 37.1% of its isolates being
      resistant to ampicillin, streptomycin, chloramphenicol and tetracyclin. There was
      a distinct increase in the frequency of multiresistant strains, from 9.7% in 1990
      to 22.9% in 1994. Of 88 such strains, 78.4% corresponded to serogroup B, whereas
      only 4.5% to serogroup D. Of the antimicrobial agents traditionally considered
      elective, only cotrimoxazole maintained acceptable resistance levels (4.4%).
      Resistance to fluoroquinolones or 3rd-generation cephalosporines was not
      detected. CONCLUSIONS: The increasing frequency of Typhimurium, a highly
      resistant serotype, restrains the elective antimicrobial agents to cotrimoxazole
      in children and fluoroquinolones in adults. 3rd-generation cefalosporines may be
      a good alternative in case of therapeutic failure.

PMID- 9035709
TI  - [Diagnosis of 4 cases of intestinal microsporidiosis in AIDS patients].
AB  - BACKGROUND: Most of the latest clinical and epidemiologic studies indicate that
      microsporidiosis and above all Enterocytozoon bieneusi cause approximately 7-50%
      of otherwise unexplained diarrhea in HIV-infected patients. Four cases of
      intestinal microsporidiosis in AIDS-patients are reported. METHODS: Detection of
      spores of microsporidiosis in stool samples from HIV-infected patients was
      performed by the following techniques: 1) light microscopy, using Kokoskin's
      modification of the Weber trichrome stain; 2) electron microscopy, for
      confirmation (only available in one case), and 3) indirect immunofluorescence
      assay (IIF), performed on all positive samples. Rabbit polyclonal antibodies anti
      Encephalitozoon cuniculi, anti-E. hellem and anti-E. (Septata) intestinalis were
      used to eliminate the possibilities of presence of microsporidiosis other than E.
      bieneusi. RESULTS: Detection of spores of microsporidiosis by trichrome stain was
      positive in all samples from the 4 patients. By elimination, IIF confirmed the
      presence of Enterocytozoon bieneusi in all 4 cases. E. bieneusi was identified by
      electron microscopy in the only case available. Three patients had CD4+
      lymphocyte counts < 100 x 10(6)/l and one < 500 x 10(6)/l. All had AIDS and three
      of them were homosexual. Two patients remained positive for microsporidiosis for
      almost 5 months. CONCLUSIONS: Despite the very few cases described in Spain,
      these preliminary data lead us to believe that intestinal microsporidiosis should
      be considered as an possible cause of diarrhea in our country also, and mainly in
      acute immunodeficiency patients.

PMID- 9035710
TI  - [Colonic tuberculosis as a cause of rectal bleeding in 2 patients with HIV
      infection].
AB  - BACKGROUND: Extrapulmonary tuberculosis is a relatively frequent disease in
      patients with HIV infection. This may be observed coinciding with pulmonary
      involvement or without diagnostic data of the same. Within extrapulmonary
      involvement, gastrointestinal involvement is one of the least frequently observed
      and its diagnosis is very difficult due to the scarce clinical suspicion because
      of the unspecific symptomatology. METHODS: Segmentary colonic tuberculosis was
      diagnosed in two patients presenting rectal bleeding. The diagnosis was neither
      clinically nor endoscopically suspected and only histologic and microbiologic
      study of the biopsies led to establishment of the diagnosis. Pulmonary
      involvement was also seen in one of the 2 patients. RESULTS: Medical treatment
      was initiated following the diagnosis. The evolution was good in one patient,
      while the other developed a picture of massive rectal bleeding requiring surgical
      resection following which the patient died due to complications. CONCLUSIONS:
      Colonic tuberculosis is an infrequent disease in patients with HIV infection.
      Only a high index of clinical suspicion along with adequate histopathologic and
      microbiologic study of all the colonic lesion biopsies can establish the real
      frequency of this disease in this group of patients.

PMID- 9035711
TI  - [Curative treatment with fluconazole in 5 cases of invasive candidiasis].
AB  - BACKGROUND: Amphotericin B is the treatment of choice for invasive and
      disseminated Candida sp. infections. Fluconazole is an antifungal drug with less
      toxicity. Because of its pharmacokinetic properties, fluconazole can be specially
      useful in the treatment of invasive candidiasis. Although it is useful in several
      forms of candidiasis, its efficacy in deep-seated candidal infections is not
      totally proved due to the lack of comparative studies with amphotericin. In order
      to contribute new data about the usefulness of fluconazole in the treatment of
      invasive candidiasis, we report 5 patients which cured with this antifungal drug.
      METHODS: The clinical records of those patients with invasive candidiasis that
      cured with fluconazole were retrospectively reviewed. RESULTS: Fluconazole was
      used in 2 patients after detecting toxicity to amphotericin. Fluconazole was used
      from the beginning in the other 3 patients. None of the patients were
      neutropenic. All the patients cured without recurrence. CONCLUSIONS: In this
      series, the employment of fluconazole was a non-toxic and effective alternative
      to amphotericin B in nonneutropenic patients with invasive candidiasis.

PMID- 9035712
TI  - [Serologic diagnosis of severe non-bacterial pneumonia and acquired in the
      community].
AB  - BACKGROUND: The aim of this study was to evaluate the profitability of the
      serology, especially against Streptococcus pneumoniae and Chlamydia sp., in the
      community pneumonia with hospital admission. METHOD: Descriptive and
      retrospective study. One hundred fifty-five pair of sera of 129 patients adults
      and 26 patients with less of 15 years with pneumonia were analysed. Antibody
      against respiratory virus, Coxiella burnetii, Mycoplasma pneumoniae, Legionella
      pneumophila, Chlamydia sp. and S. pneumoniae were investigated. RESULTS: The
      serology diagnosis was obtained in 58 patients (37.4%) (42 [32.6%] adults and 16
      [61.5%] children; p = 0.006). The pneumonia most frequently detected was caused
      by M. pneumoniae (21 cases; 13.5%), followed by Chlamydia spp. (13, 8.4%), S.
      pneumoniae (8, 5.2%) and mixed infection in other 7 cases. Detection of
      antibodies against pneumococcus and Chlamydia sp. improved as a whole in 8.4%
      (from 29% to 37.4%), a 10.9% (from 22.5 to 32.6%) in adults and none case in
      children. Moreover, a major proportion of mixed infection and by syncytial
      respiratory virus in children (19.5 and 11.5%, respectively) versus adults (1.6
      and 0%, respectively; p < 0.1) was observed. CONCLUSION: With the detection of
      antibodies against Chlamydia spp. by indirect immunofluorescence and capsular
      polysaccharide pneumococcal by enzyme-immunoanalysis increased the etiologic
      diagnosis of the community pneumonia.

PMID- 9035714
TI  - [Oncogenic mechanisms of Epstein-Barr virus].

PMID- 9035713
TI  - [2 cases of toxocariasis (visceral larva migrans)].
AB  - BACKGROUND: Different epidemiological studies have demonstrated that specific
      anti-Toxocara antibodies are detected in the serum of a high percentage of the
      Spanish population. But very few clinical cases of visceral larva migrans are
      being confirmed. METHODS AND RESULTS: Two cases of visceral toxocarosis, in two
      sisters, are described. In the first, the prevailing clinic was swelling of
      joints and upper respiratory tract symptoms; and asthma and cutaneous allergic
      manifestations in the second patient. Both cases presented with an elevated blood
      eosinophil count, high levels of total IgE and high titlers of anti-Toxocara
      antibodies. All symptoms disappeared after treatment with diethylcarbamazine and
      they remain asymptomatic several months after. CONCLUSIONS: In pediatric
      population, toxocarosis should be ruled out in every patient with respiratory
      symptoms, allergic cutaneous manifestations and elevated blood eosinophil count.
      The anti-Toxocara antibodies assay is of great value in establishing the
      diagnosis of this parasitic disease.

PMID- 9035715
TI  - [Pneumatocele, pleural effusion and pneumothorax in nosocomial pneumonia].

PMID- 9035716
TI  - [Cavitated pulmonary nodules in a patient infected with the HIV virus].

PMID- 9035717
TI  - [Corneal crystalline image in patient with keratoplasty].

PMID- 9035718
TI  - [Is HVH-8 the etiologic agent for Kaposi's sarcoma?].

PMID- 9035719
TI  - [Evaluation of CPS ID2 medium].

PMID- 9035720
TI  - [Calculation of production costs].

PMID- 9035721
TI  - [Autolimiting acute meningococcemia].

PMID- 9035722
TI  - [Salmonella septic arthritis in a hemophiliac with AIDS: aggressive treatment].

PMID- 9035723
TI  - [Streptococcal septic shock secondary to peritonitis].

PMID- 9035724
TI  - [Salmonella D spontaneous peritonitis in a cirrhotic patient with
      hepatocarcinoma].

PMID- 9035725
TI  - [Infection of the urinary tract caused by Neisseria cinerea].

PMID- 9035726
TI  - [Strategies for rationing the use of antibiotics in hospitals].

PMID- 9035727
TI  - [Infection of soft tissues of the trunk: diagnosis using CT].

PMID- 9035728
TI  - [Inducing conformational changes in thrombin by ligands as a way of regulating
      its activity].
AB  - This review summarizes data on changes in thrombin conformation induced by
      various ligands including hirudin, hirugen, similar acidic peptides, fibrinogen,
      thrombomodulin, heparin, antithrombin, prothrombin, and platelet receptor.
      Studies of enzyme kinetics, spectroscopy, X-ray structure, and thermodynamics of
      thrombin complexes with various ligands indicate that the thrombin molecule
      undergoes conformational changes. Possible mechanisms of allosteric regulation of
      thrombin activity by high molecular weight ligands are discussed which can be
      important during physiologic or pathophysiologic reactions of the organism.

PMID- 9035729
TI  - [Basal membrane proteins].
AB  - The review summarizes recent achievements in biochemistry of basal lamina which
      is highly specialized structural element of extracellular matrix. Structural and
      functional characteristics of main basal lamina proteins are reviewed including
      collagen type IV, laminin, nidogen, and heparan sulfate-containing proteoglycans.
      Special attention is paid to characteristics of structure and biochemical
      composition of renal glomerular basal lamina which is one of the main components
      of renal filtration barrier. Possible methods of investigation and
      characterization of new basal lamina proteins are discussed which help in
      understanding of biochemical composition of this structure.

PMID- 9035730
TI  - [Effect of prooxidants on nitric oxide formation in murine liver, treated with
      bacterial lipopolysaccharide].
AB  - Coinjection of citrate iron complex (7.5-10 mg iron/kg) with Escherichia coli
      lipopolysaccharide (LPS) inhibited generation of nitric oxide in the liver of
      mice caused by LPS-dependent synthesis of inducible NO-synthase (iNOS).
      Coinjection of hydroquinone, pyrogallol, or CCl4 with LPS also inhibited NO
      generation in the liver. Inhibition of LPS-dependent of NO synthesis in the liver
      by all these agents and iron can be due to their pro-oxidant effects on
      metabolism of this tissue. These pro-oxidants rapidly activate synthesis of low
      molecular weight antioxidants; LPS-dependently generated active oxygen forms in
      the liver of treated animals, which causes iNOS synthesis, are inactivated by the
      antioxidants; thus, accumulation of active oxygen species is decreased and iNOS
      synthesis is inhibited.

PMID- 9035731
TI  - [Effect of dielectric permeability of culture media on the kinetics of the ATP
      hydrolysis reaction, catalyzed by Ca2+-transporting ATPase, solubilized from
      smooth muscle cell membrane].
AB  - Transport Ca2+,Mg(2+)-ATPase was solubilized from myometrial plasma membrane and
      purified by calmodulin-sepharose 4B affinity chromatography; the effect of
      dielectric permeability of incubation medium on kinetics of ATP hydrolysis by
      this enzyme was studied. Various concentrations of dimethylsulfoxide, ethanol,
      acetone, and dioxane (up to 10%) caused various dose-dependent inhibition of
      enzymatic ATP hydrolysis. The correlation between specific activity (A) of
      Ca2+,Mg(2+)-ATPase and dielectric permeability of the incubation medium (D) did
      not depend on the nature of organic solvents and was satisfactory approximated by
      similar lines in the Laidler-Scatchard coordinate system, i.e., ln(A) versus 1/D.
      Decrease in polarity of incubation medium (changes in D from 73.05 to 68.80)
      decreased the initial maximal rate of enzymatic reaction for ATP and Mg2+ and
      increased apparent Km for these compounds. Decrease in ionic strength of
      incubation medium from 100 to 25 mM KCl decreased the maximal initial rate of ATP
      hydrolysis for Ca2+ and increased the apparent Km for this cation. The data are
      discussed in conjunction with a model of transport Ca2+,Mg(2+)-ATPase active site
      structure.

PMID- 9035732
TI  - [Connection between the level of transferrin in blood plasma and the level of
      malondialdehyde in mouse liver].
AB  - To study possible correlation between plasma transferrin content and level of 2
      thiobarbituric acid-reactive substances (malonic dialdehyde (MDA)) in the liver
      of mice, these parameters were assayed during brombenzol-induced lipid
      peroxidation and when this process was inhibited by zinc-metallothionein (zinc
      MT). In 24 h after brombenzol injection (0.5-2 g/kg intraperitoneally), mice had
      decreased blood transferrin concentration and increased MDA level in the liver.
      On the contrary, in 24 h after the zinc-MT injection (1-4 mg/kg
      intraperitoneally), blood transferrin concentration was 2-3-fold increased and
      liver MDA content was 2-3-fold decreased. The effects of zinc-MT were observed
      even in brombenzol-injected animals. Zinc-MT injection increased total
      transferrin content in the blood and decreased glycosylation of this
      glycoprotein. Changes in blood transferrin content negatively correlates (r = 
      0.75) with changes in liver MDA. The data confirm that plasma transferrin can
      participate in regulation of tissue lipid peroxidation.

PMID- 9035733
TI  - [Stability of hydrophobic nuclei of protein molecules depending of the degree of
      packing].
AB  - The values of free energies for the formation of hydrophobic cores with different
      degree of packing of nonpolar side chains have been calculated. It has been shown
      that the difference between the values of free energy for tightly packed cores
      inaccessible to water solvent molecules and the values of free energies for less
      tightly packed hydrophobic cores whose surface is in contact with the water
      solvent, is 50-60 kJ/mol and coincides with the value of the enzyme free energy
      change during its interaction with the substrate.

PMID- 9035734
TI  - [Specific properties and primary structure of BASP1 protein, initially detected
      in neuronal axonal terminals].
AB  - The BASP1 protein is one of the acidic (pI 4.3-4.6) acid-soluble brain proteins;
      it is predominant in growth cones and presynaptic regions of neurons. This group
      also includes GAP-43/B-50 neuronal protein. However, primary structures of BASP1
      and GAP-43/B-50 are different. Hydrophobicity of BASP1 protein is due to N
      terminal myristic acid residue. BASP1 molecules purified from various animal
      species possess significant regions of homology; however, polyclonal antibodies
      raised against BASP1 from various species were species-specific. Hence, BASP1
      molecules of various animals species include specific antigenic determinants
      located outside of the homology regions. Apart from brain, BASP1 was detected in
      several other tissues including lymphoid organs (spleen, thymus), kidney, and
      testis. Physico-chemical characteristics of brain BASP1 (myristoylation, pI, and
      isoforms) were identical with the proteins from other tissues. This suggests that
      BASP1 can have similar functions in various tissues.

PMID- 9035735
TI  - [Composition of HIV-1 B-epitopes and heterologous T-cell epitopes. I. Maintenance
      of antigenic properties of HIV-1 B-epitopes].
AB  - Peptides were synthesized combining an immunodominant B-cell epitope from gp41 of
      HIV-1 with heterogenous T-cell epitopes from tetanus toxoid or hepatitis B core
      antigen with no spacer bridge between epitopes. The antigenic properties of the B
      cell epitope within the composites were evaluated. The majority of the rabbit
      sera against the immunodominant B-cell epitope from gp41 recognized the B-cell
      epitope of gp41 and its composites as closely related structures. The comparative
      study of the composite peptide recognition by HIV-1 antibody positive human sera
      revealed that 82% of them similarly recognized a single gp41 epitope and its
      composites. The difference in the affinity values for the B-cell epitope from
      gp41 and its composites was less prominent than the difference between the
      affinity values for the single peptides derived from the immunodominant region of
      gp41. This indicates that the B-cell epitope from gp41 was not changed by fusion
      to heterologous amino acid sequences. The evaluation of the immunogenicity of the
      composites would reveal whether the antigenic characteristics can be of help in
      the selection of the components of multivalent peptide vaccines.

PMID- 9035736
TI  - [Composition of HIV-1 B-epitopes and heterologous T-cell epitopes. II. Combined
      analysis of immunogenicity of composite peptides in rabbits].
AB  - Rabbits were immunized with a mixture of linear cojoined peptides (composites)
      combining an immunodominant B-cell epitope from gp41 of HIV-1 (amino acids 593
      604) and a heterogeneous T-cell epitope from tetanus toxoid or hepatitis B core
      antigen. HIV-1 B-epitope in the context of the composites induced HIV-1 specific
      antibody response, while no antibodies were produced in response to the peptide
      representing single HIV-1 B-epitope. Competition ELISA and ELISA of HIV-1 peptide
      omission analogous demonstrated that immunization induced antibodies of the
      correct specificity. T-Cell epitopic components also elicited potent antibody
      production. T-Cell epitopes appeared to be immunodominant. However, HIV-1
      specific antibody response was not suppressed, on the contrary, antibody response
      against HIV-1 B- and heterologous T-cell epitopes developed in parallel. Cellular
      responses against composite peptides and/or their components were induced in all
      animals. The ability to develop cellular response against T-cell epitopes from
      the composites determined the efficacy of humoral response against the composites
      including HIV-1 specific one. Animals with strong cellular responses rapidly
      developed maximum antipeptide antibody titers. The immunization results imply
      that colinear fusion of B- and T-cell epitopes yielded bivalent multiepitopic
      products in which the immunological properties of the individual components were
      maintained and desired immunogenic properties were obtained. Immunogenicity of
      the composite peptides corresponded to that expected from the study of the
      composite antigenic properties.

PMID- 9035737
TI  - [Two components of sodium-azide insensitive Mg2+,ATP-dependent Ca2+ transport in
      ureteral smooth muscle membrane structures].
AB  - The effects of Ca(2+)-precipitating anions (oxalate and phosphate) and effective
      inhibitors of endo/sarcoplasmic reticulum calcium pump (thapsigargin and
      cyclopiazonic acid) on azide-insensitive (5 mM) Mg2+,ATP-dependent Ca2+
      accumulation in microsomes of ureter smooth muscle cells were studied. Oxalate (0
      20 mM) and phosphate (0-60 mM) stimulate Mg2+,ATP-dependent Ca2+ accumulation.
      Thapsigargin and cyclopiazonic acid at 100 nM and 20 microM, respectively,
      completely inhibited (i.e., down to the level in the absence of oxalate) Ca2+
      accumulation activated by 10 nM oxalate. These inhibitors only partially
      inhibited Ca2+ accumulation activated by 40 mM phosphate. Mg2+,ATP-dependent Ca2+
      accumulation in microsomes, which is inhibited by thapsigargin and cyclopiazonic
      acid and activated by oxalate or phosphate, can result from functioning of
      calcium pump in endoplasmic reticulum of ureter myocytes. The inhibition
      constant, Ki, was calculated by the method of Hill and it was 0.3 nM and 0.2
      microM for thapsigargin or cyclopiazonic acid, respectively. Mg2+,ATP-dependent
      Ca2+ accumulation in microsomes, which is insensitive to thapsigargin or
      cyclopiazonic acid and activated by phosphate, can result from functioning of
      calcium pump in plasma membranes of ureter myocytes.

PMID- 9035738
TI  - [Kinetic modeling of the mechanism of allosteric interactions of restriction
      endonuclease EcoRII with two DNA segments].
AB  - The effect of correlations between kinetic parameters of two inducible substrates
      on allosteric activation of EcoRII endonuclease hydrolysis of one substrate was
      studied. The pairs of DNA duplexes were constructed that were the substrates of
      EcoRII restriction endonuclease or their analogs and had different kinetic
      constants of interaction with the enzyme; the effects of their concentrations on
      mutual hydrolysis induction were studied. A kinetic mechanism is suggested
      considering the allosteric effects of two DNA recognition sites on dimeric
      molecule of EcoRII. Mathematic modeling was used to analyze the kinetic mechanism
      and evaluate optimal characteristics of the inductor. Thus, activation increases
      when (i) substrate concentration decreases, (ii) enzyme binding of two inductor
      or substrate molecules decreases, (iii) binding of one substrate molecule
      increases versus binding of one inductor molecule, and (iv) kcat of the enzyme
      substrate complex including on substrate and one inductor increases.

PMID- 9035739
TI  - [Inhibitors of the ADP/ATP antiporter induce two Ca2+-dependent uncoupling
      systems in rat liver mitochondria].
AB  - Effect of an ADP/ATP antiporter inhibitor carboxyatractylate on permeability of
      inner mitochondrial membrane was studied. Carboxyatractylate induced two
      uncoupling systems: Ca(2+)-dependent pore and another system which was sensitive
      to an inhibitor of calcium uniporter ruthenium red (apparently, Ca(2+)-recycle).
      Extent of Ca(2+)-recycle induction correlates with a fraction of mitochondrial
      population which underwent permeabilization; inhibition of permeabilization by
      cyclosporin A prevents induction of the recycle. Thus, induction of Ca(2+)
      dependent pore is direct consequence of carboxyatractylate binding to
      mitochondria whereas induction of Ca(2+)-recycle is indirect. Both uncoupling
      systems are induced by carboxyatractylate concentrations which are specific for
      ADP/ATP antiporter. The data suggest that the antiporter can directly participate
      in the formation of Ca(2+)-dependent pore in inner mitochondrial membrane.

PMID- 9035740
TI  - [Control of the rate of the glucokinase reaction by its elementary stages].
AB  - Limitation of an enzymatic reaction by its elemental steps is characterized by so
      called control coefficients for (quasi)stationary reaction rate. Established
      paradigm of "limiting step" cannot describe the control of glucokinase reaction.
      Flux control is distributed between several elemental steps (ATP binding, ADP
      release, etc.); this distribution significantly changes when reaction conditions
      are modified, i.e., changes in glucose or ATP concentrations occur. At about 1 mM
      ATP and 2-5 mM glucose, impact of ATP binding stage on total flux control is
      positive and it exceeds 50% if ATP binds after glucose. However, if ATP binds
      before glucose then control coefficient for ATP binding is negative. At high
      substrate concentrations, impact of product dissociation on flux control becomes
      significant. Distribution of control between elemental steps cannot be predicted
      by changes of Gibbs energy or by the rate constants of elemental steps.

PMID- 9035741
TI  - [Measurement of ATP in intact Escherichia coli cells, containing recombinant
      firefly luciferase].
AB  - Recombinant firefly luciferase was expressed in E. coli and its properties inside
      the intact cells were studied. At low concentrations, antibiotic polymyxin B
      increases permeability of E. coli cell membrane and concentrations of luciferase
      substrates inside the cells can thus be varied. Effect of intracellular ATP
      concentrations on intensity of bioluminescence was studied. Recombinant cells
      expressing the firefly luciferase gene can be used for investigation of
      substances which influence synthesis and hydrolysis of ATP inside the cells and
      cell membrane transport.

PMID- 9035742
TI  - [Participation of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate in reactions of
      bacteria on oxidative stress and their persistence in macrophages].
AB  - In aerated medium, Corynebacterium ammoniagenes cells accumulate 2-C-methyl-D
      erythritol-2,4-cyclopyrophosphate (MEC) during heat shock and in the presence of
      O2--generating compounds or ozone. The ability to accumulate MEC was genetically
      transformed from C. ammoniagenes to E. coli XL-1; transformed E. coli (2-31
      clone) accumulates MEC in the presence of glucose and glucose oxidase (generation
      of H2O2) or benzylviologen (generation of O2-); the viability of transformed
      bacteria inside the murine peritoneal macrophages also significantly increases.
      However, model conditions of phagosomes of warm-blooded animals (NO + H2O2 + O2-)
      did not cause MEC accumulation by C. ammoniagenes but increased the formation of
      polyphosphate which can be due to selective oxidative aberration of biosynthetic
      processes. Growth rate of Acanthamoeba castellanii on solid medium with bacterial
      lawn was not significantly different in C. ammoniagenes, C. ammoniagenes with
      preaccumulated MEC, E. coli XL-1, and E. coli 2-31 and did not depend on the
      accumulation of MEC by bacteria. Unlike the recipient E. coli strain, the
      transformed 2-31 clone synthesizes two nonpolar lipids (Rf = = 0.85 and 0.75; TCL
      on Silufol in hexane) and carotinoid pigments; this can be due to changes in
      metabolic pathways of isopentenylpyrophosphate that can be a precursor of MEC
      biosynthesis. Thus, MEC is involved in bacterial responses to certain components
      of oxidative stress and in bacterial persistence inside the macrophages.

PMID- 9035743
TI  - [Random necessity, transcription initiation, induction of differentiation and
      need for randomness].
AB  - Review of recent achievements in investigations of transcription initiation
      mechanisms reveals that random commitment of cells to proliferation is due to the
      complexity of these mechanisms. In multicellular organism, this is not only a
      problem but is the basis of generation of required variety of cells.

PMID- 9035744
TI  - [Mitochondrial transport of nucleic acids. Participation of the benzodiazepine
      receptor].
AB  - The models of mitochondrial transmembrane nucleic acid transfer are discussed.
      According to this hypothesis, mitochondria can exchange their nucleic acids by
      two possible mechanisms including either intermitochondrial fusion and fission or
      transmembrane transport. In the latter case, important roles for mitochondrial
      benzodiazepine receptor and factors that regulate activities of its components
      (mitochondrial porin and adenine nucleotide translocator) are suggested. Nucleic
      acids can be transported through a Ca(2+)-dependent pore that can be one of the
      functional states of mitochondrial exchange of genetic material. Problems like
      cellular aging, apoptosis, proliferation, mitochondrial diseases, multidrug
      resistance, intracellular traffic, and mitochondrial heredity are discussed
      considering an important role of mitochondrial benzodiazepine receptor in these
      processes.

PMID- 9035745
TI  - In vitro degradation of a poly(propylene fumarate)-based composite material.
AB  - We investigated the in vitro degradation of a novel degradable polymeric
      composite material being developed to function as a temporary replacement for
      trabecular bone. This material is based on a mixture of poly(propylene fumarate)
      cross-linked by N-vinyl-pyrrolidone and includes sodium chloride and beta
      tricalcium phosphate. Using an in vitro test in simulated body fluids, the
      compressive strengths and compressive moduli of two composite materials increased
      with degradation time and remained above the minimum values acceptable for
      trabecular bone substitutes. A compressive strength of 21.3 (+/- 0.4) MPa and a
      compressive modulus of 696 (+/- 53) MPa were measured after twelve weeks for a
      composite material with initial strength of 18.0 (+/- 4.6) MPa and initial
      modulus of 113 (+/- 40) MPa. This unexpected phenomenon may prove to be useful
      for orthopaedic applications.

PMID- 9035746
TI  - [Characteristics features of the ultrastructure of liver cells in various
      morphological types of animals and their significance].

PMID- 9035747
TI  - [The effect of low molecular weight ovarian peptides on the reproductive function
      during its partial inhibition by food deprivation].

PMID- 9035748
TI  - [Changes in the systemic hemodynamics during electric stimulation of ventral
      regions of the medulla oblongata].

PMID- 9035749
TI  - [Dynamics of coupled pulse activity of neurons from the motor cortex of
      conditioned cats].

PMID- 9035750
TI  - [Opposite effects of adaptation to physical exertion on the myocardium and
      skeletal muscle. Ca-transporting system of the sarcoplasmic reticulum and the
      enzymes of the antioxidant defense].

PMID- 9035751
TI  - [The effect of fibronectin on generation of superoxide anion by neutrophils
      during food poisoning and experimental salmonella endotoxemia].

PMID- 9035752
TI  - [Invertory mechanism of the changes in Na,K-ATPase activity in myocardium
      cytoplasmatic membranes during critical stage of compensatory hyperfunction of
      the heart in adult and aged rats].

PMID- 9035753
TI  - [Differences in the stimulation of NO synthesis during heat shock in genetically
      different rats].

PMID- 9035754
TI  - [The effect of catalase inhibitor 3-amino-1,2,4-triazole on coupled oxidative
      phosphorylation and the state of adenyl system in liver mitochondria of albino
      rats].

PMID- 9035755
TI  - [The effect of sedatin--a synthetic analog of dermorphin--on cell division in
      cornea and tongue epithelium of albino rats].

PMID- 9035756
TI  - [Correction with cordaron of changes in beta-glucosidase activity induced by
      toxic effect of strophanthin K and simulated heart decompensation].

PMID- 9035757
TI  - [The effect on central dopaminergic structures of various hydrazides of
      phosphorylated carbonic acids and diaziridines].

PMID- 9035759
TI  - [Bactericidal properties of out-of-focus NAG laser radiation].

PMID- 9035758
TI  - [The role of relationship between the epiphysis and the sympathetico-adrenal
      system in the depressogenic effect of reserpine].

PMID- 9035760
TI  - [Antigenic properties of outer membrane porins in Yersinia genus].

PMID- 9035761
TI  - [Immunocorrecting, antianemia, and adaptogenic effects of polysaccharides from
      Melilotus officinalis].

PMID- 9035762
TI  - [The effect of incorporation of various doses of 131I on the immunological
      reactions].

PMID- 9035763
TI  - [The effect of dexamethasone dose and cell population composition on in vitro
      production of tumor necrosis factor and interleukin-6 by mononuclear cells in
      peripheral blood of man].

PMID- 9035764
TI  - [Cytotoxic activity of complexes formed during an interaction between tumor
      necrosis factor-alpha and alpha2-macroglobulin].

PMID- 9035765
TI  - [Synthesis and phosphorylation of gastric proteins in cells of human gastric
      carcinoma].

PMID- 9035766
TI  - [The effect of verapamil on the growth and sensitivity to vincristine of human
      tumor transplanted into kidney capsule of mice].

PMID- 9035767
TI  - [Damage to breast cancer cells after the use of radiotherapy modifiers].

PMID- 9035768
TI  - [The effect of 5-HT1 and 5-HT2 serotonin receptor agonists and antagonists on
      predator aggression in wild Norway rats].

PMID- 9035769
TI  - [Expression of human IgE-binding factor (sCD23) in Escherichia coli cells].

PMID- 9035770
TI  - [Direct antiatherogenic effect of garlic].

PMID- 9035771
TI  - [Pathogenesis of hypertrophic cardiomyopathy in a fetus during insulin-dependent
      diabetes in a mother].

PMID- 9035772
TI  - [Virus-induced morphological changes in arterial vessels of rabbits with herpetic
      keratoconjunctivitis and in patients with generalized herpetic infection].

PMID- 9035773
TI  - [The use of porous polysulfone as a new material for implantation into the
      orbit].

PMID- 9035774
TI  - [Morphological characteristics of the stomach of microtinae rodents from
      ecologically dangerous regions].

PMID- 9035775
TI  - [Comparative evaluation of activity of proteolytic enzymes used in the surgery
      for the debridement of suppurated wounds].

PMID- 9035776
TI  - Esthetic correction of PFM restorations: a case report.

PMID- 9035777
TI  - Adverse effects of NSAIDs.

PMID- 9035778
TI  - Prevention of hip fracture: a goal for the year 2000. Proceedings of the 1st
      Merck International Symposium on Osteoporosis. Paris, December 1, 1995.

PMID- 9035779
TI  - [Current legislation in public health--an example for post-modern social
      ethics?].
AB  - Social ethics of affirmative postmodernists are discussed in relation to recent
      German health care legislation. It could be shown that: 1. the health care
      legislation 1989 and 1993 only partially fulfills the postmodern call for
      "cultivation of individual responsibility", 2. both laws largely fail to enforce
      the principle of subsidiarity, and 3. postmodernist thinking is weak on the
      question of global strategies but strong In the area of individualism and
      subjectivity. We conclude that postmodern social ethics are useful to compensate
      areas largely neglected by recent German health care legislation, rather than
      that the legislation is an example of postmodern social ethics.

PMID- 9035780
TI  - [Patient satisfaction as health care outcome--the example of surgical correction
      of the nasal septum].
AB  - BACKGROUND: Presented is a study, that investigates the relevance of patient
      satisfaction as evaluative criteria for effectiveness of medical measures
      exemplary in patients who underwent surgery for a deviated nasal septum. MATERIAL
      AND METHODS: A standardised Instrument was specifically developed and pretested
      (n = 30). In January 1995 all working members of a German sickness fund
      hospitalised between March and September 1994 for ICD-470 (deviated nasal septum)
      were surveyed retrospectively by means of a written questionnaire. The response
      rate was 85.2% (n = 334, 88.8% male; medium age: 35.2 years, average length of
      stay: 6.5 days). Descriptive and multivariate analysis were performed. RESULTS:
      10.6% of the study population reported a complete decrease of preoperative
      symptoms (100% relative improvement), whereas in 7.9% no alleviation of nasal
      related symptoms was reported. 45.2% of the patients are satisfied with the
      outcome of septal surgery, 35.6% are satisfied to a limited extent, 19.2% express
      their "dissatisfaction". Multivariate analysis was performed to investigate the
      main determinants of patient satisfaction. It can be seen that the percentage of
      satisfied patients increases if there is a large alleviation of that symptom
      cited as main reason for undergoing nasal surgery, if the discomfort caused by
      nasal packings is small and if the overall burden of nasal associated symptoms is
      low postoperatively. CONCLUSION: Patient criteria for evaluating the surgical
      outcome are plausible and include dimensions also relevant from the clinician's
      perspective. Therefore, the integration of systematic patient-oriented
      assessments into the evaluation of medical care seems to be a promising approach.
      It might be used i.e. to identify high priority areas in the context of quality
      management.

PMID- 9035782
TI  - [Plea for conversion of youth medical service to "school medical service"].
AB  - In many towns and communities, the work of the school and youth medical service
      is based almost exclusively on the performance of school entrance mass
      examinations. Even though among experts essential aspects of these examinations
      are increasingly criticised with regard to contents and method, they still
      require a considerable amount of skilled personnel. In the following article, two
      suggestions are made concerning a reform of the school and youth medical service:
      (1.) The early mass screening "U9" which at present is carried out by the local
      physicians will be expanded so that it corresponds to the same criteria as the
      present school entrance mass examination. The school and youth medical service
      then would only take action concerning those children who have not gone through
      the "U9" on the date set for enrollment in elementary school. (2.) The mass
      examinations are handed over completely to the established physicians within the
      scope of the "U9". For this purpose, the "U9" would have to be reorganized and
      modified. Both considerations aim at the abandonment of the school entrance
      medical mass examination. Objective of the described suggestions is to maintain
      the capacity in terms of time and personnel of the school and youth medical
      service for the tasks of health education, promotion and care which have been
      hardly taken into account up to the present. At the same time, this modification
      offers a chance to solve many of the current problems concerning content and
      method.

PMID- 9035781
TI  - [Backache in East and West Germany].
AB  - On the basis of data of the East German Health Survey (1991/92) and regional
      studies from West Germany (Bad Sackingen 1990, Lubeck 1991/92, Bad Sakingen
      1993/94) results on the prevalence of back pain, other rheumatic complaints and
      general health problems are compared. East German respondents report on back pain
      and all other rheumatic complaints definitely less often than West German
      respondents but suffer equally from general health complaints. Apart from the
      differences in the prevalence of rheumatic complaints there are remarkable
      structural analogies between East Germany and the West German cities. In any
      region, the back is the most often affected part of the body, followed by the
      neck, the shoulder, and the knee. Beyond that, there are similar age-related and
      sex-specific differences in prevalence rates of rheumatic complaints. In the
      groups of elderly people, a pattern of declining or constant prevalence rates can
      be noticed with many complaints. However, there are differences in pain intensity
      and functional limitations between East and West. The East German respondents
      particularly mention mild pain more rarely than respondents of the West German
      cities. They also report fewer functional limitations. This may indicate that in
      East Germany people attach less importance to rheumatic pain and deal with it in
      a different way. Possibly, the differences in prevalence can be explained
      thereby. To what extent they reflect real differences in morbidity cannot be
      clarified by the present data.

PMID- 9035783
TI  - [Alcohol in Munich secondary school students--a study for dissemination of
      experiences, knowledge, attitude and behavior].
AB  - The Munich Community Health Service (Medical School-Service Department) conducted
      an alcohol prevention project in ten public secondary schools. The 423 pupils (11
      17 years of age) filled in a questionnaire on alcohol and discussed it afterwards
      under the guidance of a school physician and a teacher using guideline
      information. The results of the survey are presented in this paper. Additionally,
      suggestions for transferring the results to conceptualize and carry out
      preventive measures are made. The results indicate that the first experience with
      alcohol occurred early in life. One-fifth of the sample had already tried alcohol
      at the age of six. Immediate effects of alcohol (e.g. state of drunkenness) were
      experienced by 35.7 percent of the sample group. Kiosks, shops, and beverage
      stores were named most frequently as sources for alcohol. The sources of social
      support varied with respect to sex and age. With increasing age of the children,
      parents were contacted less frequently whereas the role of peers increased. The
      present results supply possible paths of action for the development of successful
      prevention strategies, e.g. by pointing out the early age of onset as well as
      specific sources of alcohol acquisition.

PMID- 9035784
TI  - [Status of the management of addicted patients--results of an expert survey as
      the basis for health policy decisions].
AB  - 457 (39%) of 1172 experts filled in a questionnaire on the need of public health
      care for addicted persons in a defined region. About 80% of the experts reported
      a need of care above average for alcoholics, only 63% for illicit drug consumers.
      Prevention and public relations work is according to 70% of the experts a matter
      of prime importance. More than 70% of the experts see a special need of care for
      addicted persons who have been unemployed for a long time or already at a young
      age. An additional need for care also exists for long-term care methods and on
      location work by social workers. About 68% of the experts emphasize the need for
      additional care for addicted persons with psychiatric disorders. The differences
      between the investigated regions are discussed.

PMID- 9035785
TI  - [Forensic psychiatry evaluation of mental competence--from psychopathological
      case analysis to assessment].
AB  - According to the restrictive juridical guidelines only severe mental disturbances
      can lead to a repeal of legal capacity. For the forensic-psychiatric expert the
      analysis of the psychopathological features is the decisive point, not a certain
      diagnosis. This proceeding is demonstrated by examples. Criteria are provided
      which may be helpful for the assessment.

PMID- 9035786
TI  - [Epidemiology of individual front tooth gaps in exiled Tamilians].
AB  - During the period from 1986 to 1993, 254 Tamilian patients were examined by the
      Department of Public Health at Wuppertal. These patients had come from Sri Lanka
      as refugees applying for political asylum in the Federal Republic of Germany. In
      more than 60% of the patients isolated front tooth gaps were observed, an
      incidence that was significantly higher than in a control group of asylum seekers
      from countries other than Sri Lanka, and much higher than the incidence of
      traumatic tooth loss reported in the literature. To the authors the aetiology of
      this tooth loss remains largely unexplained, since the bulk of the medical
      histories given by the patients did not correlate with clinical and x-ray
      evidence. Considering that medical and especially dental causes for the loss of
      the teeth can be excluded, social, cultural, religious, or even political causes
      may be responsible for this anomaly.

PMID- 9035788
TI  - ["Full shift light masonry work". Apparently a crux--social medicine epicrisis].

PMID- 9035787
TI  - [Toxicologic evaluation of pyrethroids in indoor air: demonstrated with the
      example of cyfluthrin and permethrin].
AB  - Pyrethroids have varying activities depending on vehicle or route of
      administration (oral, dermal, inhalational). Specific features like the sensory
      irritation potential of the alpha-cyano-pyrethroids on the respiratory tract can
      only be quantified adequately by inhalation testing. Thus equitoxic dosages can
      vary between inhalative and oral application, especially for alpha-cyano
      pyrethrolds. The no-effect values for chronic exposures derived for permethrin
      (type I pyrethroid) and cyfluthrin (type II pyrethroid) show clearly, that each
      pyrethroid has to be considered as an individual substance toxicologically, and
      that any extrapolation from the oral to the inhalative route should only be done
      after a thorough assessment of the specific toxicological profile. The study of
      simulated pest control measures on carpets pretreated with permethrin showed,
      that no significant enrichment of permethrin in total dust could be seen from a
      carpet additionally treated with pyrethroids. The missing correlation between
      absolute (mg pyrethroid/m3 air) and relative (mg pyrethroid/kg dust)
      concentrations in air-borne dust as well as the low degree of translocation of
      pyrethroids from carpets (only about 0.044% x m(-2) x h(-1) of the cyfluthrin
      applied to the carpet can be regarded as possibly respirable) prove, that
      analyses of pyrethroids in household sedimented dust ("vacuum cleaner bag
      analyses") without knowing the absolute surface concentration and respective air
      concentrations are of little value for risk assessment. The data allow the
      conclusion, that a scientific assessment of health risks is only possible based
      on absolute concentrations of pyrethroids in indoor air.

PMID- 9035789
TI  - The query corner. Collateral vessels.

PMID- 9035790
TI  - Women with noise-induced hearing-loss: an invisible group?
AB  - The aim of this qualitative study was to describe, from the perspective of women
      with noise-induced hearing loss (NIHL), their experiences of noise as a threat to
      health and their having to live with a hearing disability, i.e. behaviours,
      thoughts and emotions in auditory demanding situations. Ten women, patients with
      NIHL at the Department of Audiology, Boras' Hospital in Sweden, were selected to
      form a heterogeneous sample. A taped in-depth interview, lasting from 45 minutes
      to 1 hour, was conducted with each woman. The verbatim transcribed interviews
      were consecutively analysed using a method influenced by the tradition of
      grounded theory. Four categories emerged in the process of analysis. These
      categories were labelled: lack of awareness, ambivalence, controlling and
      avoiding coping strategies and stigmatization. The category 'lack of awareness'
      concerned the women's perceptions of the risks of noise on hearing, the lack of
      efforts on the part of the women to apply for financial compensation for their
      NIHL, the lack of an awareness of individual's right to have healthy work-place
      and to receive professional help for hearing impairment. Also lacking was the
      concept that hearing impaired individuals have the right to participate in the
      community on similar conditions as non-hearing impaired people. This lack of
      awareness was identified as a core category relating to the other categories:
      ambivalence, controlling and avoiding coping strategies and stigmatization. The
      women's expressions indicated ambivalence concerning the cause of the hearing
      disability and, also, how to manage the consequences of it: the women in the
      study seemed to alternate between feelings of hopelessness/resignation and a
      state of acceptance of the hearing disability. Furthermore, the women alternated
      between blaming themselves and blaming others for the cause of the hearing loss,
      indicating a change between internal and external locus of control. Also, the
      women alternated between controlling and avoiding strategies in coping with
      demanding auditory situations. The coping strategy chosen by the women in a
      specific situation intended to prevent or minimize stigmatization, i.e. 'to pass
      as normal' and thereby to maintain a positive self-image of normality. Despite
      this, the women often perceived negative and stigmatizing attitudes from others,
      which reinforced their feelings of ambivalence in how to manage the situation.
      The hypothesis based on the present pilot study, that women with NIHL are more
      likely to pass themselves off as normal hearing and therefore might be less
      likely to be reported in studies of NIHL than men, needs to be further tested in
      a larger sample.

PMID- 9035791
TI  - [Psychophysiological correlates of increasing the work ability of human operator
      owing to the programmable correction of the functional status].
AB  - There has been studied application of a complex approach to development of
      automated ways to gain contactless psychophysiological correction of functional
      status and improvement of performance of working up operators. The
      psychophysiological support of operator consisted in combined presentation of
      functional music, surf noise and pulsed dynamic green lighting under a special
      program built-up on the principle of biological feedback of heart and respiration
      rates. The individually adaptable audio and visual pulses on the programme showed
      a rather high efficiency as was confirmed by the change in the set of
      psychophysiological indices (heart rate, arterial pressure, cutaneogalvanic
      reaction, accommodation volume, critical rate of flicker fusion,
      electroencephalogram), and subjective SAM (self-feeling, activity, mood)
      estimates in the course of extended operator's activity.

PMID- 9035792
TI  - [Effect of alcohol intake on the ability to pilot aircraft].
AB  - During the initial 4 hours after alcohol intake at a dose of 1.9 g/kg aircraft
      operators displayed disturbances in the psychic processes and functions
      responsible for each (from information reception and processing up to decision
      making and building-up the controlling actions) structural elements in their
      activity resulting in considerable limitation or a complete failure to pilot
      aircraft. Main disorders included inability to correctly analyse flight situation
      and loss of skills to automatically control simulator, a sudden depletion of
      psychophysiological reserves and deterioration of operator's reliability. Less
      elaborated professional skills appear to be the most vulnerable.

PMID- 9035793
TI  - [Prediction of the central effect of pharmacological preparations in a hyperbaric
      environment].
AB  - A new method for predicting the central effects of pharmacological preparations
      in hyperbaric helio- and nitrogen-oxygen environments takes into consideration
      the dynamics of changes in excitability of different structures of the brain in
      animals compared with EEG and behavioural symptoms of the high pressure nervous
      syndrome (HPNS), and levels of the barometric pressure. The concept of the
      central effect of preparations under hyperbaric conditions should be taken into
      account while rendering the medicamentous assistance to aquanauts directly
      exposed to elevated pressure. Besides, it was shown that the strategy of
      searching protectors against NSHP and nitrogen narcosis may consist of selecting
      substances which will adequately recuperate shifts in the brain excitability due
      to these hyperbaric pathologies.

PMID- 9035794
TI  - [The relation of circadian variations of heuristic behavior and CNS
      radioresistance in animals].
AB  - There has been studied the influence of g-radiation (60Co, 62.5 Gy, craniocaudal)
      on circadian dynamics of heuristic behaviour (the elements of rational
      discriminative activity) of male white rats. There has been found equivocal
      nature of radiation action: mostly manifestations of some symptoms of neurologic
      disturbances observed in definite daily periods make difficult realizing
      behavioural act, but in the other cases such event is not observed (acrophases of
      both processes coincide). After disappearance of observed neurologic
      manifestations of central nervous system damage (symptoms of early transitory
      neurologic disturbances) during the short period of time after exposure to
      radiation the inversion of circadian rhythm of heuristic behaviour has not been
      found. The changes are expressed in significant increase of values of extremums
      and mesor in comparison with control groups not exposed to radiation. By 30
      minute after exposure the process loses signs of rhythm, acquires smooth
      character and mesor response significantly decreases.

PMID- 9035795
TI  - [Effects of adaptogenes on some indices of functional state of the body on
      occupational radiation exposure].
AB  - There have been presented the data of studying the body functional state of
      individuals being long contact with the ionizing radiation sources and assessing
      the effectiveness of prevention and correction of the revealed disorders with the
      help of adaptogenes. It is found that ordering of eleuterococcus as well as some
      new biologically active substances which include vitamins amino acids, organic
      acids, phospholipids, microelements (ammivit, Ascocept, Hianaya) for the course
      of treatment makes a contribution to a significant, acceleration of adaptation to
      the extreme factors of the professional activity of the mentioned group of
      individuals. It is indicated that ammivit, Ascocept and Hianaya out perform
      eleuterococcus.

PMID- 9035796
TI  - [Results of integrated tests of the facility to disinfect gaseous environment of
      orbital stations].
AB  - The microbiological safety control with the use of the Potok 150M facility aboard
      operational orbital station of Mir series is discussed. The test results
      indicated that the facility does not actually influence the content of harmful
      microscopic admixtures in a gaseous medium of the mock-up compartments of the Mir
      orbital station, elevates slightly the noise level during operation and provides
      the highly effective purification of gaseous medium from dust and microorganisms.
      It allows us to conclude that an application of the Potok 150M facility aboard
      operational station shows promise.

PMID- 9035797
TI  - [Effect of weightlessness on the mother-fetus system (results of embryological
      experiment NIH-R1 abroad the "Space Shuttle"].
AB  - Female rats were exposed to weightlessness in the mid-deck of US "Space Shuttle"
      in the period between days 9 to 20 of pregnancy and examined on Earth post
      flight. No significant structural anomalies threatening the life and normal
      development were found in newborn rats carried by mothers under the conditions of
      weightless exposures. Water, Na, K, Ca, Fe and Cu contents in fetal and placental
      tissues of the flight animals were not changed. Differences between the flight
      and ground-based synchronous controls, or the rates of formation of the fetal
      skeleton were not revealed. Comparison of these data with results of the
      experiment aboard biosatellite "Cosmos 1514" in which female rats stayed in
      weightlessness from day 13 to 18 of pregnancy indicates that the two-fold
      increase of space flight duration did not add changes in the state of fetuses.

PMID- 9035798
TI  - [Methodological aspects and clinicophysiological substantiation of applying the
      hypoxic therapy].
AB  - The paper gives the methodical and clinicophysiological substantiation of the
      hypoxic therapy, a new nonmedicamentous method of body sanitation, raising its
      physiological reserves, prevention of pathological states, treatment and medical
      rehabilitation of patients based on breathing air with a reduced O2 partial
      pressure for the purposes. Health damaging and improving effects of hypoxic
      hypoxia, perspectives of this therapy from the standpoint of prevention and
      treatment of myocardial ischemia are discussed. Results of the fundamental
      studies unveiling the mechanisms of ischemic, reperfusion-induced disorders of
      myocardium and assessing possibilities of their blockage of the hypoxic therapy
      are considered. On the literary and own evidence, the authors analyse
      effectiveness, merits and drawbacks of different (mountain/climatic, hypobaric,
      normobaric) techniques of hypoxic therapy. Informative criteria for determination
      of hypoxic resistance of the patient with coronary diseases and choice of
      individual hypoxic regimen are rationalized.

PMID- 9035799
TI  - [The new approaches to diagnosis, treatment and expertise of chronic hepatitis in
      pilot personnel].
AB  - The causes of pilot personnel disqualification associated with chronic hepatitis
      are analysed. Until recent times insufficiently complete examination of the
      flying personnel suffered from the chronic hepatitis gave no way of proposing the
      individual programmes of treating such illness as the chronic persisting
      hepatitis, chronic cholecystic hepatitis, chronic cholecystic hepatitis,
      alimentary and medicamentous injuries. This may be responsible for the high level
      of disqualification of the flying personnel. Another important factor was the
      lack of the preparations allowing one to administer differentiated therapy. These
      studies permitted, with the use of such preparations as vetoron, heptral,
      ursosan, to improve significantly both clinical and expert indices in the pilot
      with chronic hepatic diseases.

PMID- 9035800
TI  - [New approaches to clinico-diagnostic and expert appraisal of the benign
      hyperbilirubinemia in pilot personnel].
AB  - The study was aimed at improving the new clinico-diagnostic and expert approach
      to the benign hyperbilirubinemia in the pilot personnel. The 41 pilots of
      different aviation categories have been studied. There is indicated clinic of the
      benign hyperbilirubinemia in correlation with the presented laboratory indices.
      It is determined that laboratory diagnostics is the method selecting an
      examination of the given state, whereas the ultrasound scanning is critical to
      the diagnostic of the benign hyperbilirubinemia because it allows one to assess
      the whole structure of the hepatic tissue. Ultrasound examination proved to be
      the reliable technique of additional control of the liver state in the pilot
      personnel in a period between medical control commission.

PMID- 9035801
TI  - [Making of the clinicophysiological diagnosis within the system of medical flight
      certification].
AB  - Adaptation responses were evaluated in flying personnel during medical
      examination with the use of simulators of the main dynamic factors of flight.
      Utility of assessing the adaptive reactions of the cardiovascular system by their
      physiological "cost" has been demonstrated. Parameters of the normal
      cardiovascular response to moderate hypoxia in altitude chamber have been
      established. On the basis of accumulated data, more sensitive and informative
      criteria for assessment of the functional state of the human organism are
      proposed for clinicophysiological diagnostics within the system of medical
      certification of flying personnel.

PMID- 9035802
TI  - [Morbidity rate and early diagnosis of gastrointestinal tract pathology (GIT) in
      aircrew].
AB  - The epidemiological investigations done in the Air Army for six years (1986-1993)
      showed that the morbidity of GIT in aircrew is on the second place among the
      inner organs diseases. The data of examination of 1438 pilots, navigators and
      other specialists are given. All of them were examined at the department of
      medical air examination. The use of active endoscopy allowed to make an early
      diagnosis of GIT diseases. Their formation rather often took place under extreme
      conditions of the flight. There is a natural increase of GIT morbidity together
      with an increase of the total amount of flight hours. The authors had worked out
      effective measures of prophylaxis, treatment, rehabilitation and improvement of
      professional medical selection as to GIT diseases in aircrew.

PMID- 9035803
TI  - [The effect of the 120-day antiorthostatic hypokinesia on the functional state of
      female thyroid].
AB  - Investigations of eight healthy female volunteers aged 26-37 in 120-days
      antiorthostatic hypokinesia (AOH, -5 degrees) gave original data about
      peculiarities of adaptation and functional state of female thyroid and the
      thyreotrophic activity of adenohypophysis. The test-subjects were divided into
      two equal groups. Group 1 administered a set of countermeasures including
      exercise and pharmacy. In the other group, no health control was used. By days 90
      100 in AOH thyroid glands of the females were slightly more compact but remained
      diffuse. Thyroid sizes were not altered. Chemical/biochemical examination did not
      elicit any noteworthy shifts in the thyreotrophic activity of hypophysis or
      thyroid function in the bedrested females. The countermeasures did not enhance
      the thyroid function. Results of the investigation point to the completion of
      thyroid adaptation of females by days 90-100 in AOH.

PMID- 9035804
TI  - [A case of Oberling's retroperitoneal xanthogranuloma in pilot].
AB  - A rare case of retroperitoneal mass identified in the pilot, aged 48, is
      described. There has been noted the complexity of differential diagnosis between
      the benign and malignant process associated with the given type of tumor which
      led to some problems when making an expert decision. The tumor was found to be
      non-removable, however, considering the good clinical state of the pilot, he was
      permitted of flying activity which he continues to perform successfully more than
      10 years. The pilot state remains good which confirms the benign character of the
      process. The observation is of great interest both clinically and from the flight
      surgeon's appraisal standpoint.

PMID- 9035805
TI  - [The problem of adaptation to space flight].
AB  - The presented paper is the review of the theoretical aspects of adaptation as
      applied to the factors of space flight. The aspects which are used in the
      professional selection and in the training of cosmonauts are discussed. The
      theoretical basis of the methods for diagnostics of functional states of the body
      and for increase of the reserve abilities of cosmonauts is studied. The authors
      suggest the working of the problem of adaptation to more complicated space
      flights including interplanetary travels is in sight. The authors conclude that
      at the present creation of the general conception of adaptation to space flight
      as to the complex of extreme factors is necessary.

PMID- 9035806
TI  - [The significance of visual analyzer in controlling the standing posture in
      individuals with the spastic form of child cerebral paralysis while wearing
      "Adel" suit].
AB  - The paper discussed the results of stabilographic examination of the children
      suffered from the spastic form of child cerebral paralysis (CCP) treated by means
      of graded wearing of "Adel" suit which is a modification of the "Penguin"
      spacesuit. There has been studied the state of 30 children before treatment with
      the use of "Adel" suit and after the treatment as well as following the several
      courses of wearing the suit. Besides the patients, eleven healthy volunteer
      subjects (control group) were examined. There have been obtained the results
      pointing to the fact that in the healthy persons when they try to achieve the
      standing posture the leading role pertains to visual analyzer, at the same time,
      in the patients with spastic form of CCP the realization of standing posture
      depends upon the severity of the motor function disorders. When in the process of
      control stabilographic examination the patients suffered from spastic form of CCP
      demonstrate the significant role of the visual analyzer in achieving the standing
      posture, the use of the "Adel" suit is most desirable. The use of the "Adel" suit
      in the CCP patients with a decreased role of visual analyzer in achieving the
      standing pose as it was found under control examination enhances its significance
      in controlling the position of the center of gravity of the body.

PMID- 9035807
TI  - [The regulation of cell volume: the mechanisms, coupled cellular reactions and
      pathophysiological significance].
AB  - A review contemplates as a whole the problem of regulation of the cellular
      volume. The first part of the review considers the influences inducing
      alterations in the cells volume on account of changes in the tonicity of
      extracellular milieu and cytoplasm. The review elucidates the ways of
      implementing the fast and slow regulatory volume increase as well as decrease
      (RVI, RVD). The volume increase seems to enhance cells' proliferative ability due
      to activation of ions transport. The volume decrease needs further
      investigations. The last chapter of the review considers pathophysiological
      significance of the volume regulation in hyponatremia, diabetes, neutrophil
      activation.

PMID- 9035808
TI  - [The activity of the motor units of the feline esophagus under cooling].
AB  - The background activity of the oesophagus motor units (MUs) was found to depend
      on respiration and to be facilitated in cooling. The MUs patterns of discharges
      involved a phasic activity and a tonic one. The firing rate of the MUs increased
      during expiration. A negative correlation was found between the phasic MUs firing
      rate and the skin temperature.

PMID- 9035809
TI  - [Elements in the organization of the vasomotor center (on the 125th anniversary
      of its discovery by F. V. Ovsiannikov)].

PMID- 9035810
TI  - [The effect of periodic stretching of the smooth-muscle cells on the expression
      in them of contractile-phenotype marker proteins].
AB  - Cyclic mechanical stretching of the rabbit aortic smooth muscle cells induced a
      serum-independent increase in the h-caldesmon expression. The expression was more
      obvious in the cells grown on laminin. The data obtained suggests that the cyclic
      stretching specifically activates a serum- and matrix-independent expression of h
      caldesmon. The mechanical stimulation seems to contribute to the maintenance of
      the VSMC differentiated phenotype.

PMID- 9035811
TI  - [The participation of the serotoninergic system in regulating the activity of the
      central glutamatergic/aspartatergic and GABA-ergic synapses].
AB  - Selective lesion of the serotoninergic system diminished the synaptic uptake of
      3H-L-glutamic acid and 3H-DL-aspartic acid, as well as the Na+(-dependent)
      binding of 3H-L-glutamic acid in the cortex and the brain stem. The data obtained
      suggest an ability of the serotoninergic system to modify presynaptic processes
      in amino-acidergic neurons of the CNS.

PMID- 9035812
TI  - [The contractile activity of the isolated mesenteric artery at different pH
      values of the perfusion solution].
AB  - Tonus of the proximal, medial and distal portions of the rat mesentery artery did
      not respond to the pH shifts in the perfusion fluid. However, the pH shift to 6.6
      reduced the vessel sensitivity to noradrenaline (NA) as well as its constrictor
      response to electrical stimulation (ES). The pH shift to 7.8 augmented the medial
      and distal segments' dilatation in response to the ES at the NA concentration 10
      5. The proximal portion had different responses. The data obtained suggest that
      acidosis exerts a depressive effect upon the mesentery artery's responsiveness to
      the NA and ES, and that the alkalosis exerts a potentiating effect upon the ES
      induced vasodilatation.

PMID- 9035813
TI  - [The action of noradrenaline, vasopressin and deoxycorticosterone acetate on the
      activity of the Na+,K+ pump in the veins and arteries of different vascular
      regions].
AB  - Noradrenaline and vasopressin were shown to stimulate the Na+/K(+)-pump activity
      both in veins and in arteries, whereas desoxycorticosteronacetate did not
      increase it in pulmonary and mesenteric vessels and even depressed it in the
      mesenteric vein. There is different potentiation exerted by noradrenaline and
      vasopressin upon the Na+/K(+)-pump activity in veins and in arteries. The data
      obtained suggest the regional heterogeneity in the Na+/K(+)-pump activity in
      neurohormone activated blood vessels.

PMID- 9035814
TI  - [The effect of the initial (controllable) tonus of arterial vessels on the
      formation of systemic pressor reactions].
AB  - A significant decrease of systolic and diastolic effects occurred when initial
      level of the blood pressure had been elevated from 60 to 200 mm Hg with mesathone
      and from 70 to 185 mm Hg with polyglukine in anaesthesized rats. A reverse linear
      correlation was found between the above parameters at a high degree of connection
      for both agents. "Vascular" and "cardiac" mechanisms of revealed relationships
      are discussed.

PMID- 9035815
TI  - [The effect of polarization of the vascular wall on the ion transport and
      contractile activity of the rat tail artery].
AB  - The effects of the blood velocity upon the responsiveness of blood vessels seem
      to be based on the processes inducing a deforming of the diffuse part of a double
      electrical layer at the border between the blood and vascular wall of the rat
      tail artery. Salts of polyvalent metals were found to diminish the negativity of
      the transmural potential and to diminish the contractile activity and the tone of
      the blood vessels. Heparin exerted an opposite effect.

PMID- 9035816
TI  - [Regional blood flow distribution in waking rats under elevated external
      temperature].
AB  - The heart output (HO) was estimated by means of the 133 Xe clearance in the rat
      tail, the rat being placed either in a narrow hole or a spacious box. In the
      hole, the HO rose from 24 to 36 ml/(min.100 g), in the box the HO portions of
      skeletal muscles and bones were by 3.8 and 2.0 times lower; in the hole, their
      reduction was insignificant; the lung radioactivity rose from 4 to 20% (the hole)
      and to 42% (the box) which suggests a considerable increase in the blood flow
      through arterial-venous anastomoses.

PMID- 9035817
TI  - [The regulation of blood neutrophil functions by C-reactive protein and serum
      amyloid P].
AB  - The effect of C-reactive protein on oxygen metabolism and lysosomal activity of
      the human blood neutrophils was found to depend on its ability to conform and to
      render both the pro- and anti-inflammatory results. The serum amyloid P exerted
      mostly a consistent anti-inflammatory effect.

PMID- 9035818
TI  - [Changes in the electroretinogram of Campbell rats with the development of
      hereditary retinal degeneration].
AB  - We studied the dependence of amplitudes of a- and b-waves of electroretinogram on
      intensity of light stimulus in Campbell rats with inherited retinal degeneration.
      On 20-th-29-th day after birth the amplitude of these waves in Campbell rats is
      smaller than in Wistar rats. On 30-th-40-th day response significantly decreases,
      down to complete disappearance of reaction. Weak response appears only to
      stimulus with the maximal luminance. According to decrease of amplitude of the a-
      and b-waves of the ERG, Campbell rats are practically blind at 40th day of
      postnatal life. The analysis of the form of whole ERG curve using the Fourier
      transformation allowed us to establish, that in Campbell rats on 20-th day after
      birth the amplitude of the first and second harmonics grows with increasing of
      stimulus luminance. At 30-th day the amplitude of the second harmonic in Campbell
      rats is much smaller than in Wistar rats and does not vary with increasing of
      stimulus luminance.

PMID- 9035819
TI  - [The mechanisms of serotonin participation in the smooth-muscle reactions of the
      trachea].
AB  - Serotonin was shown to induce a dose-dependent enhancement of the tonus of the
      rat and guinea pig trachea smooth muscle: low concentrations facilitated the
      contractile activity, whereas high doses relaxed the muscle via transmural
      stimulation of nervous fibres. The serotonin receptors were found to be located
      at the postganglionic cholinergic fibres and metasympathetic neurons of the
      trachea intramural ganglia. Presence of the receptors at the trachea smooth
      muscle cells seems to be highly improbable.

PMID- 9035820
TI  - [Trypsinogen as a modifier of peptidergic influences on the secretion of the
      gastric and pancreatic glands].
AB  - I.v. administration of trypsinogen potentiated the pentagastrin-induced secretion
      of gastric glands and reduced the leu-enkephalin effect upon them in the fistula
      dogs. Intraperitoneal administration of trypsinogen enhanced the pepsinogen
      synthesis by the gastric glands, did not change the hydrolases activity in
      pancreas homogenate in rats.

PMID- 9035821
TI  - [The regulatory mechanism of the activity of the saccharase-isomaltase complex of
      the brush border in rat enterocytes].
AB  - The data obtained suggests a possibility of regulation of the brush borders
      sucrase-isomaltase complex activity of the enterocytes. This ability seems to be
      a general biological phenomenon as it has been found both in birds and in
      mammals. The findings corroborate the theory of the functional blocks.

PMID- 9035822
TI  - Ethics ... National Institutes of health has endorsed a controversial needle
      exchange research project.

PMID- 9035823
TI  - [Ocular refraction in Zaire].
AB  - PURPOSE: to determine frequencies of refractive errors in Zairian blacks and to
      investigate the influence of race upon refraction. METHODS: we examined the
      records of all patients seen at the department of Ophthalmology from 1963 to
      1972. Refraction was measured by objective (skiascopy) or subjective methods.
      RESULTS: we found 4326 patients with ametropia, about 16% of the total. The
      records of 2594 Zairian patients with refractive errors were compared to those of
      1417 non Zairian black patients and 315 Caucasian patients. The frequency of
      spherical refractive errors in Zairian black patients was 56%: (simple myopia:
      33% myopia over 5 D: 1%, hypermetropia: 22%), astigmatism was seen in 44% (myopic
      astigmatism: 31% and hypermetropic astigmatism: 11%). The data of Zairian were
      similar to those of non-Zairian black patients. Spherical refractive errors in
      Caucasian patients were found in 46% of the patients (simple myopia: 19%, myopia
      over 5 D: 2%, hypermetropia: 25%). Astigmatismatic errors were seen in 54%
      (myopic astigmatism: 27%, hypermetropic astigmatism: 24%, mixed astigmatism: 3%).
      Hypermetropia increased with age in all groups, but slightly earlier in Zairian
      patients. CONCLUSION: Although the data of refractive errors did not show
      significant differences between Zairian and Caucasian patients, hypermetropic
      astigmatism seems to be less frequent and myopia more frequent among Zairian
      patients.

PMID- 9035824
TI  - A timely change of fentanyl patch.

PMID- 9035825
TI  - Environmental illness and multiple chemical sensitivity.

PMID- 9035826
TI  - [Etiology of cerebral palsy].
AB  - The "perinatal asphyxia" is regarded to be one of the causes of cerebral palsy,
      though in the very most of the children with cerebral palsy there is found no
      hypoxia during labour. It should be mentioned, that the definition of "perinatal"
      and "asphyxia" neither are unic nor concret. And also there is no correlation
      between nonreassuring fetal heart rate patterns and acidosis in fetal blood with
      the incidence of cerebral palsy. Numerous studies in pregnant animals failed in
      proving an acute intrapartal hypoxia to be the origin of the cerebral palsy.
      Myers (1975) describes four patterns of anatomic brain damage after different
      injuries. Only his so called oligo-acidotic hypoxia, which is protracted and
      lasts over a longer time is leading to brain injury, which can be regarded in
      analogy to the injury of children with cerebral palsy. Summarising the update
      publications about the causes of cerebral palsy and the studies in pregnant
      animals there is no evidence that hypoxia during labour may be the cause of
      cerebral palsy. There is a great probability of a pre(and post-)natal origin of
      brain injury (for instance a periventricular leucomalacia found after birth)
      which leads to cerebral palsy. Short after labour signs of a so called "asphyxia"
      may occur in addition to this preexisting injury and misrepresent the cause of
      cerebral palsy. Finally the prepartal injury may cause both: Cerebral palsy and
      hypoxia.

PMID- 9035827
TI  - [Comparison between age-dependent (Wald alpha program) and age-independent (Ulm
      index) analysis program for prenatal detection of Down's syndrome with serum
      markers].
AB  - An age-dependent analytic program (Alpha-Software from Wald) was compared to an
      age-independent Index (Ulm-Index) in order to determine effectivity of detection
      in prenatal screening for Down's Syndrome in 7060 pregnant women. The rate of
      accuracy was similar in both analytic programs (6 from 7), but, the rate of false
      positive results was twice as high using the Ulm-Index (14.7 versus 7.7%). The
      higher rate of amniocentesis necessary using the age-independent Ulm-Index
      apparently does not justify this method for prenatal screening of Down's
      Syndrome.

PMID- 9035828
TI  - [Prenatal chromosome analysis using the FISH technique allows fetal aneuploidy
      detection within a few hours].
AB  - Last years evaluation of fluorescence-in-situ-hybridization (FISH) allowed
      detection of chromosomal abnormalities by using DNA probes, binding to
      chromosomes in the nucleus. Because it is possible to directly examine interphase
      nuclei, FISH-technique, in contrast to traditional cytogenetic analysis has the
      advantage of small loss of time in case of urgent decisions on perinatal
      management. Karyotyping was performed on fetal cells, obtained from 72
      pregnancies after amniocentesis, by both classical cytogenetics and fluorescence
      in situ hybridization using commercially available kits which utilise the alpha
      satellite probes for chromosomes 13 + 21 and 18. The classical cytogenetics
      demonstrated that the fetal karyotype was normal in 67 cases and abnormal in 5
      cases (four with trisomy 21 and one with a translocation trisomy 18). With the
      FISH-technique it was possible to obtain accurate diagnosis of trisomy 21 within
      24 hours of sampling. The distribution of the number of signals in the
      chromosomally normal and abnormal fetuses was significantly different, but we
      were not able to identify the fetus with translocation trisomy 18. We conclude
      that in the investigation of fetuses with ultrasonographic diagnosed
      malformations, FISH provides a rapid technique for detection of numerical
      chromosomal aberrations, but replacement of classical cytogenetics is not
      possible because of its limitations for identification of subtle structural
      chromosomal abnormalities.

PMID- 9035829
TI  - [Possibilities for false-negative findings in trisomy 21 screening with FISH].
AB  - In approximately 5% of individuals with Down syndrome aneuploidy results from a
      chromosomal rearrangement. FISH analysis on chromosome metaphases and interphase
      nuclei of 5 individuals with Down syndrome carrying different types of chromosome
      21 translocations demonstrated the diagnostic efficiency of this method. By use
      of different commercially available chromosome 21 specific probes we were able to
      show that only the cosmid probe specific for the Down syndrome critical region
      (DCR) in 22qll gave reliable results for interphase analysis of trisomy 21, while
      the use of chromosome 21 centromere- or of painting probes carry a high risk of a
      false-negative diagnosis in translocation trisomy 21.

PMID- 9035831
TI  - [Perinatally-induced hypoxic-ischemic encephalopathy? Possibilities of
      retrospective evaluation from the neuropediatric viewpoint].
AB  - This paper analyzes the feasibility of determining retrospectively, from a
      neuropediatric standpoint, whether an existing neurological disorder can be
      traced back to a perinatal hypoxic-ischemic encephalopathy. In principal, we can
      assume that there is a correlation between this time and pathogenesis of the
      brain injury on the one hand and the neurological symptoms on the other if these
      conditions are fulfilled 1. In the first days of live term infants revealed
      cerebral symptoms (like abnormality of muscle tone and consciousness and
      seizures) which manifest themselves in a typical sequence and are combined with
      involvement of other organ systems. In pre-term infants the clinical signs are
      often not clearly definable. 2. The subsequent neurological disorder after the
      primary symptoms must be a spastic-less commonly in term infants a dyskinetic
      one. 3. Lesions typical for the child's gestational age are visible on magnetic
      resonance imaging.

PMID- 9035830
TI  - [Stimulation trials of trophoblast cells in vitro using PP14].
AB  - Cytotrophoblast cells were isolated from human term placenta after cesarean
      section by fragmentation of villous tissue with trypsin and DNAse I. Trophoblast
      cells fuse in vitro to syncytiotrophoblast cells and progesteron is released.
      Placental Protein 14 (PP14) was incubated (300 micrograms/ml PP14 in 6 ml
      solution (6 x 10(6) cells) with the cytotrophoblast cells. Production of
      Progesteron is increased in PP14-trophoblast cell cultures compared to untreated
      trophoblast cells.

PMID- 9035832
TI  - [Team work, the central axis in intensive care units].

PMID- 9035833
TI  - [Quality of life of patients with myocardial ischemia].
AB  - In this work we intend to determine the variations produced on the quality of
      life observed and perceived, in the patients with ischemic cardiopathy (IC) whose
      severe process was treated in the Intensive Care Unit of the Hospital General of
      Albacete between January and July 1993. A transversal descriptive study on a
      population of 117 cases was designed. 19 variables were defined, and a summary
      number scale was designed to determine the quality of life globally. In the
      results obtained after correcting the initial scale, as it was excessively
      discriminatory, we found that 47.7% of the individuals suffer a deterioration of
      their quality of life observed after suffering an IC, 55.4% remain the same, and
      2.9% improve. According to the modifications in the quality of life perceived by
      the patients and interviewers, 24.3% of the first ones show a deterioration in
      front of 22.4% perceived by the second ones. To conclude we can say that the
      suffering of an IC limits considerably many aspects of their quality of life,
      there is enough discrepancy between the quality of life observed and the one
      perceived.

PMID- 9035834
TI  - [Descriptive statistics: description and representation of variables].

PMID- 9035835
TI  - [Functional health patterns and nursing diagnosis in intensive care units].
AB  - The evaluation of the critically ill patient to develop a suitable care plan is
      one of the main objectives of the practices of Medico-Surgery for students of
      third year of the nursing degree. So as to be able to detect all the needs in the
      patients and settle priorities in their care we have carried out a physical
      evaluation and the 11 health functional patterns of Gordon (1982), which has
      allowed us to formulate the most frequent diagnosis of nursing in the patients
      hospitalized in the Intensive Care Units of the Hospital Son Dureta of Palma de
      Mallorca. The collection of data for the evaluation of the patterns of
      autoperception, adaptation to stress and to the family, has been scarce due to
      the critical situation of the patient and the tendency of nursing professionals
      to register the evaluation data which indicate alterations of the physical
      condition of the patient. The incapacity for self-care and the risk for infection
      have been the nursing diagnosis which all the patients of this study have shown.

PMID- 9035836
TI  - [Coronary fibrinolysis: quality care].
AB  - Coronary fibrinolysis through intravenous via is a usual technique in ICU
      worldwide, it is a procedure of controlled risk which provides great benefits to
      patients who undergo such technique. The role of nursing in the administration
      and control of the fibrinolytic treatment is essential. Despite that, the plans
      for fibrinolysis specific care are very scarce, if not inexistent, in the
      bibliography reviewed. The main objective of this work is identify the
      complications derived from the administration of fibrinolytic medicines through
      intravenous via. Using a chart of collected data, which goes from the admission
      of the patient to their discharge from ICU, 178 cases are studied. After the
      analysis of results, a standardization of intensive care units orientated to
      increase the assistance quality is suggested.

PMID- 9035837
TI  - 1996 International meeting on ANCA and ANCA-related diseases. The 7th
      International ANCA Workshop. Rochester, Minnesota, October 14-16, 1996.
      Proceedings and abstracts.

PMID- 9035838
TI  - [An analysis of the causes of low-efficacy treatment in type-2 diabetes mellitus
      using sulfonylurea derivatives].
AB  - Peroral sugar-reducing agents have come to be routinely used in the treatment of
      type-II diabetes mellitus. The chief representatives of this group of drug
      preparations are derivatives of sulfonylurea. However, following a certain period
      of time of effective utilization of sulfanilamides, there develops secondary
      sulfanilamide resistance. An analysis has been performed of causes of low
      effectiveness of sulfonylurea derivatives in the treatment of type-II diabetes
      mellitus. Errors in the policy of treating diabetes mellitus with the above drug
      preparations are analysed as are causes of secondary insulin dependence.

PMID- 9035839
TI  - [The treatment of non-Hodgkin's lymphomas taking into account individual
      sensitivity to the chemical preparations].
AB  - Polychemotherapy is a mainstay in the treatment of lymphoproliferative diseases.
      At the department of systemic tumour diseases there have been examined as many as
      63 patients with malignant lymphomas; individual sensibility was studied to
      antitumour drug preparations as recommended by V. P. Evtukh, A. S. Zverkova
      (1984). After courses of polychemotherapy devised with taking in account the
      individual sensibility, the immediate results and a parameter characterizing the
      relapse-free survival got improved as compared with treatments administered
      according to standard strategies, particularly so in patients with non-Hodgkin's
      lymphomas presenting with high degree malignancy in the stage of dissemination.

PMID- 9035840
TI  - [The characteristics of the rehabilitative treatment of patients with a history
      of unstable stenocardia].
AB  - While examining forty-nine patients with the history of unstable angina pectoris
      (UAP), it was established that the sanatorium stage of rehabilitation with the
      proper extension of sick leave being accorded to such patients, is indicated in
      cases of low tolerability of physical exercise (50 wt and less) when discharged
      from hospital. Those patients with prior UAP who can tolerate physical exercise
      at 75 wt and above, are recommended to resume their work. In addition,
      improvement in tolerability of physical work loads in patients with prior UAP was
      found to be accompanied by diminution in the left ventricle cavity size.

PMID- 9035841
TI  - [A comparative evaluation of the antianginal action of commercially and
      noncommercially produced validol in neurocirculatory dystonia and stenocardia].
AB  - As many as 20 patients with neurocirculatory dystonia (NCD) and 10 IHD patients
      presenting with stable exertional angina were evaluated for an effectiveness of
      antianginal action of validol tablets commercially- and noncommercially produced,
      the above tablets being of the changed composition in the latter case. Validol of
      both changed and unchanged composition had a similar transient antianginal effect
      which was higher in NCD than it was in angina pectoris. Economical as well as
      clinical effects of validol of the changed make up warrant it to be commercially
      produced.

PMID- 9035842
TI  - [The effect of the angiotensin-converting enzyme inhibitor Capoten on the volume
      regulation indices of patients with stage-II hypertension].

PMID- 9035843
TI  - [The combined pharmacological correction of oxidative homeostasis in a hypoxic
      syndrome].

PMID- 9035844
TI  - [The assessment of the psychophysiological status of patients with duodenal
      peptic ulcer].
AB  - Clinicopsychologic and psychophysiologic evaluation was done in 290 patients with
      duodenal ulcer during the stage of exacerbation. The results obtained suggest the
      levels of vegetative lability, anxiety and depression in the above patients to be
      significantly higher by comparison with those in healthy subjects. The degree of
      neuropsychic disorders depends upon the type of personal response to the illness
      which is greater in women than it is in men. Differentiated complex approach for
      the psychotherapeutic treatment of patients with duodenal ulcer permits dealing
      with their neuropsychic disorders and influencing their personal traits in a
      purposive manner, which consideration contributes to the improvement of the
      patients' soma and psyche.

PMID- 9035845
TI  - [Ethonium in the treatment of patients with gastric and duodenal peptic ulcers].
AB  - Overall thirty-six patients with gastric and duodenal ulcer were evaluated for
      the clinical effectiveness of ethonium. The results obtained showed sufficient
      effectiveness of this drug preparation in the therapy of the above medical
      conditions. The mild course of ulcer disease appears to be treatable by
      monotherapy, while moderately severe and severe courses require incorporation of
      other medicinal agents into therapeutic plans, specifically, those from the group
      of blockers H2-histaminic receptors. Ethonium is well tolerated by patients, side
      effects are rare and do not require special treatment, which facts allow it to be
      included into strategies for treating peptic ulcer.

PMID- 9035846
TI  - [The efficacy of immunomodulating therapy in patients with chronic cholestatic
      liver diseases].
AB  - The use is studied of the immunomodulating agents splenin and vilosen in a
      combined therapy of 93 patients with chronic cholestatic disorders of the liver.
      The above drug combination was found to have a positive effect on both the immune
      status and condition of microhemodynamics, with the clinical parameters getting
      improved, duration of remission lengthened.

PMID- 9035847
TI  - [The treatment of pulmonary tuberculosis patients with liver involvement].
AB  - It has been ascertained both in an experimental and clinical setting that of all
      the pathogenetic means of treatment pulmonary tuberculosis tocoferolum acetatum
      is a preparation of choice for PT patients presenting with concurrent hepatic
      pathology. This drug preparation has hepatoprotective immunomodulating effect.
      Shown for the first time is surfactant-correcting action of the drug. In a
      clinical setting, in a series of a total of 118 patients with pulmonary
      tuberculosis presenting with hepatic pathology the efficacy of tocoferolum
      acetatum was found to be superior to that of other hepatoprotectors. Tocoferolum
      acetatum eliminates the hepatotoxic reactions 2.5-3.5 times as often as
      hepatoprotectors and vitamins group B, ascorbic acid and bioflavonoids.

PMID- 9035848
TI  - [The potential pathogenetic therapy of pyelonephritis].

PMID- 9035849
TI  - [The characteristics of the treatment of newly detected pulmonary tuberculosis in
      miners].
AB  - Results are submitted on the treatment of 192 miners free from manifest signs of
      silicosis when they first presented with different forms of pulmonary
      tuberculosis. Tuberculosis in those individuals engaged in the coal industry was
      found out to poorly respond to treatment. During the period of 1.5-2 years,
      cicatrization of the cavities of decay occurred in 42.6 percent of the cases, no
      bacteria were recoverable in 50.0 percent. The treatment results were dependent
      upon the utilization of combinations of antituberculous drug preparations, routes
      of their administration and choice of pathogenetic options. The greatest benefit
      from treatment occurred with izoniazid, rifampicin, ethambutol and intrabronchial
      instillations of izoniazid.

PMID- 9035850
TI  - [The use of holotropic breathing in the treatment of chronic alcoholism].
AB  - The present paper focuses on the effectiveness of a new psychotherapeutic
      technique described under the denomination of "holotropic breath" to be employed
      in the treatment of patients with alcohol addiction. It is a modified classical
      technique under the above denomination adapted to the narcological needs. Case
      material is presented. A conclusion is drown to the effect that the above
      modified psychotherapeutic modality is an effective and useful alternative in a
      narcological setting.

PMID- 9035851
TI  - [Sexual dimorphism in osteoarthrosis deformans].

PMID- 9035852
TI  - [The efficacy of using Zanocin in infectious diseases].

PMID- 9035853
TI  - [New developments in the treatment of oral candidal infection].
AB  - There have been developed new stomatologic parodontal films (SPF) containing an
      antifungal substance CMN. Treatment of patients with acute pseudomembranous
      candidiasis, acute atrophic candidiasis and chronic atrophic candidiasis runs 4
      to 5 days instead of 7-9 with the traditional method of application of 2% levorin
      ointment; no reinfection was noted to occur. The medicinal preparation is highly
      effective and convenient for use.

PMID- 9035854
TI  - [The characteristics of the course of typhoid-paratyphoid infections against a
      background of trauma or wounds].

PMID- 9035855
TI  - [The diagnosis of allergy to industrial chemical compounds using a method of
      immunothermistometry].
AB  - An evaluation was done in those individuals engaged in the production of
      detergents, enzymic preparations, electron tubes and measuring instrumentation,
      using allergologic, laboratory methods and immunothermistometry of blood with
      allergens obtained from industrial chemical compounds. Feasibility is
      demonstrated of employing in the diagnosis of chemical allergy the
      immunothermistometry technique which was found to be superior to the known
      laboratory immunologic tests.

PMID- 9035856
TI  - [The importance of using biological test objects in studying the toxicity of
      surface-active substances].
AB  - The Azotobacter agilis [correction of azobacter agile] culture appeared to be the
      most sensitive one among the studied test objects. Buckwheat as a test plant can
      be recommended in studying the toxicity of surface-active substances.

PMID- 9035858
TI  - [The morphocytometric characteristics of the level of differentiation in cancer
      of the large intestine].
AB  - Adenocarcinoma was studied of varying degrees of histologic malignancy localized
      in the large intestine (80 cases). A set of qualitative parameters for each
      degree of differentiation have been developed with a selection of certain
      criteria, such as indices for the fraction by volume of proliferating DNA
      synthesizing cells and percentage of pathologic mitoses together with the
      cytometric parameters, having been done from the general sum of the values. The
      above characteristics reflect significantly the dynamics of development of the
      processes of malignancy; they might help, we believe, in providing an adequate
      approach for treating morbid conditions and predicting their outcomes.

PMID- 9035857
TI  - [A combination of radiotherapy and chemotherapy with platidiam and fluorouracil
      in patients with head and neck cancer].

PMID- 9035859
TI  - [A case of a combined course of meningococcal infection and viral hepatitis A].

PMID- 9035861
TI  - [A case of a benign course of Wilson-Konovalov disease].

PMID- 9035860
TI  - [Edelmann's syndrome].

PMID- 9035862
TI  - [A case of carcinoid of the pancreas].

PMID- 9035863
TI  - [The health assessment of the population of Ukraine from the viewpoint of
      potential demography and the means for a possible influence on its indices].

PMID- 9035864
TI  - [Methodological and deliberative bases for using official statistical medical
      information for supporting population health monitoring in Ukraine].

PMID- 9035866
TI  - [Debatable questions in the organization of the diagnosis of lung cancer].

PMID- 9035867
TI  - [The methodological-organizational aspects of surgical care for the rural
      population].

PMID- 9035865
TI  - [Treatment and evacuation measures to eliminate the aftermath of technogenic
      catastrophes].

PMID- 9035868
TI  - [The pathophysiological significance of the low triiodothyronine syndrome with
      increased clearance in cancer of the stomach and large intestine].
AB  - Investigations designed to study T3 pharmacokinetics under malignant tumors of
      the stomach and large intestine showed an augmented total T3 clearance, which
      fact is indicative of enhancement of the processes of 5-monodeiodezing of thyroid
      hormones. It is to be thought that intensification of T3 metabolism and rise in
      inverse T3 produced through peripheral conversion of T4 underlie the pathogenesis
      of that low triiodothyronine syndrome to be encountered in malignant tumors.
      Since the above mechanism of development of low T3 syndrome has been identified
      in traumata and infectious diseases, the changes in question might be considered
      to be one of the links in the general adaptive syndrome directed towards
      satisfaction of the phagocytosing leucocytes' requirements in the biocydic
      substrate iodine and augmentation of the production of the fat-mobilizing factor
      inverse T3.

PMID- 9035869
TI  - [Variants in the situational dynamic-type tasks in the internal disease clinic].

PMID- 9035870
TI  - [Current questions in the problem of diagnosis].

PMID- 9035871
TI  - [Langerhans cells and the immunological function of the skin].
AB  - An analysis of published literature on the skin as a multicomponent system for
      initiation of the T-cell response to a antigen is the focus of this review.
      Recent data are considered on the structure, function and genesis of Langerhans'
      cells as principal cellular elements providing representation of the antigen
      while the immune reactions initiated in the skin are running their course. An
      analysis of data on relations of Langerhans' cells to other reticular cells as
      well as to keratinocytes has been performed. Issues related to the development
      and mutual transformation of stationary cells of the lymphoid organs and
      Langerhans' cells are discussed.

PMID- 9035873
TI  - [The role of nucleic homeostasis in different pathological states of the human
      body].

PMID- 9035872
TI  - [The characteristics of the immunity status of people with arterial hypertension
      who took part in the cleanup of the aftermath of the accident at the Chernobyl
      Atomic Electric Power Station].
AB  - Clinical and immunological investigations were conducted in 70 patients with
      arterial hypertension from among those individuals having taken part in the
      elimination of the aftereffects of the Chernobyl APP breakdown in 1986-1987. The
      analysis of the results obtained showed the patients with primary and renal
      hypertension present with pathogenetic heterogeneity of the immune disturbances,
      which fact necessitates conducting rigorous immunologic monitoring for the
      methods of immune correction to be objectivized.

PMID- 9035874
TI  - [Immune system function in the participants in the cleanup of the aftermath of
      the accident at the Chernobyl Atomic Electric Power Station].
AB  - Imbalance was revealed in the proportions of T-lymphocyte subpopulations in those
      persons engaged in activity in mining employment who had been exposed to a
      complex of the radiation accident factors. Maximum reduction in the lymphocyte
      suppressor activity was recordable in those patients in whom the doses of
      radioactive irradiation received exceeded 25 s Gy. Depression was found of
      humoral immunity manifested by a drop in the absolute as well as relative numbers
      of B-lymphocytes and fall in the blood serum levels of Ig G, A. The results of
      study of clinical-biochemical and immunologic parameters of blood permit
      individualized therapies be developed, prophylactic measures to be devised to
      deal with the relevant pathologic processes and conditions in the cohorts
      examined.

PMID- 9035875
TI  - [The effect of anthropogenic changes to the environment on the course and
      treatment procedure in mental disorders in the population of the Lugansk region].
AB  - Regional features of the course of mental abnormalities are viewed within the
      framework of a notion about the exogenously organic pathoplastics of
      psychogenesis inherent in the ecological system of the Lugansk region. Those
      events are described of transitory subclinical failure of compensation in psyche
      that present certain distinctive features being region-associated. A proposition
      is substantiated to the effect that the above clinical features are to be taken
      into account of when opting for this or that treatment.

PMID- 9035876
TI  - [The embryotropic action of an industrial-frequency magnetic field].
AB  - The animals exposed to a magnetic field of industrial frequency with the level of
      induction of 250 over 4 months develop depression of their reproductive function,
      which fact manifests itself by decline in their potential of being able to
      conceive, drop in fertility because their general embryonal mortality is so high,
      their offspring lacking vital power, the numbers of deadborn being on the
      increase, their newborns dying during the first month of their life. There are
      also instances of female loss following delivery presenting with the events of
      bleeding, consequent upon disturbances in the reproductive function.

PMID- 9035878
TI  - [Changes in the hemodynamic indices of patients with juvenile hypertension and
      different hemodynamic types of circulation].

PMID- 9035877
TI  - [The immune status indices of schoolchildren in the Donetsk region].
AB  - With the purpose of studying the impact of ecological health hazard conditions on
      the juvenile organism, a total of 192 pupils of upper grades from schools in
      Donetsk, Makeyevka, Mariupol (conventionally a "dirty" zone) and 126
      schoolchildren from Artemovsk and Krasnyi Liman (conventionally a "clean" zone)
      were evaluated for the immunological status. Children from the polluted zone
      demonstrated decreased levels of lysozyme in saliva as well as of glycogen and
      acid phosphatase in leucocytes, there were also deviations from the norm in the
      peripheral blood picture. Young residents of Mariupol appeared to have the worst
      findings.

PMID- 9035879
TI  - [The correlations between the arterial and venous components of the hemodynamics
      and cerebrospinal fluid pressure in arterial hypotension].
AB  - A total of 30 patients with arterial hypotension were examined.
      Rheoencephalogrammes documented hypotension of the arterial and venous
      constituents of the brain in one third of the above patients (in those patients
      with physiological hypotension it was recordable more frequently): in one forth
      of those cases with primary arterial hypotension presenting with the cerebral
      crises, moderately severe venous and arterial hypotension was generally seen. In
      a major proportion of the examinees, a correlation was found between the drop in
      arterial pressure, vascular tension of the arterial vessels of the brain and an
      adequate state of the venous tension and liquor pressure. Roentgenography of the
      skull and ophthalmoscopy do not permit forming an opinion about liquor
      hypertension since it was not demonstrated on the computerized tomographic scans.

PMID- 9035880
TI  - [The membrane-protective action of a new preparation of n-3 polyenic acids in the
      adrenaline-damaged myocardium].
AB  - We undertook this study to evaluate effects of a long-term pretreatment with a
      new stabilized drug preparation n-3 polyunsaturated fatty acids (PUFAs) in the
      development of experimental adrenalin-induced necrosis of the myocardium. It was
      found out that the preliminary administration of PUFAs makes for a significant
      reduction in the mass of the infarcted area of the myocardium. Severely manifest
      arrhythmias were less frequently seen in treated animals, with death rates among
      them being lower than in controls, and what is more, an excess activation of the
      biomembrane lipid peroxidation and suppression of the function of the system of
      antioxidant defence, occurring in necrosis of the myocardium in an experimental
      setting, appeared to be generally preventable. It is suggested that the ability
      of n-3 PUFAs to modulate the properties of the biological membranes might account
      for the above effects.

PMID- 9035882
TI  - [The ultrastructural, histomorphological and histoenzymological changes in the
      gastric mucosa in different forms of chronic gastroduodenitis].
AB  - Investigations designed to study gastric mucosa (GM) in patients with chronic
      primary gastroduodenitis with the aid of electron microscopy showed the abnormal
      changes in the cellular, subcellular membranes and capillaries to be of the same
      type as they are in peptic ulcer (PU) though poorly manifest. Changes in GM under
      chronic atrophic gastroduodenitis (ChGD) suggested involutive changes while in
      chronic secondary gastroduodenitis (ChSGD) it was generally not different from
      the mucosa ultrastructure in healthy subjects except for changes in surface
      epithelium. Based on the histoenzymologic studies it has been ascertained that in
      ChPGD there occurs a rise in lysosomal enzymes similar to that encountered in PU,
      reflecting the intensity of catabolic processes, decrease in the activity of
      enzymes of the capillary wall and mitochondria respiratory chain against the
      background of compensatory enhancement of the activity of the glycolytic enzyme
      lactate dehydrogenase. In ChAGD the activity of all the enzymes was low, while in
      ChSGD it did not differ significantly from that in healthy subjects.

PMID- 9035881
TI  - [Changes in the unsaturated fatty acids and lipid peroxidation during the
      treatment of patients with rheumatoid arthritis].

PMID- 9035883
TI  - [The vascular bed of the liver in cirrhoses: pathogenesis and morphogenesis].

PMID- 9035884
TI  - [The effect of tactivin and the intraduodenal administration of drug mixtures on
      the efficacy of the therapy of duodenal peptic ulcer].
AB  - Incorporated into the complex of therapeutic measures to treat duodenal ulcer
      associated with Helicobacter pylori (H. p.) were tactivin and intraduodenal
      administration of drug mixtures made up of pharmaco- and phytopreparations.
      Effectiveness of treatment was to be evidenced by healing of the ulcer defect,
      elimination of H. p. from the mucous membrane, and length of clinico-endoscopic
      remission. The greatest benefit from treatment occurred when tactivin was used in
      combination with intraduodenal administration a mixture of rotocan, olazol,
      proposol, methiluracil, and trychopol.

PMID- 9035885
TI  - [The significance of periodic gastric and duodenal motor activity in the clinical
      picture and combined treatment of patients with chronic acalculous
      cholecystopancreatitis].
AB  - A total of 39 patients with chronic calculi-free cholecystopancreatitis were
      evaluated for the reoccurring motility (ROM) of the stomach and duodenum using
      the method of ionoballoonotensiocinesiography. All patients presented with
      different types ROM disturbances accompanied in most cases by duodenal
      hypertension, duodenogastric reflux and reflux-gastritis. The ROM state should be
      considered in prescribing pathogenetic combined conservative treatment.
      Principles allowing some judgement about the ROM state have been determined.

PMID- 9035886
TI  - [The classification of weakly mineralized therapeutic waters by the biological
      response of bile secretion and urination functions using multivariate
      assessment].
AB  - A scheme is proposed for the evaluation of the efficacy of the effect of those
      kinds of water containing little of mineral natural substances and having
      medicinal value, on the functions of bile secretion and urination. Using
      discriminant and component analyses, there has been formed a pragmatic
      classification of under-mineralized medicinal waters of Ukraine to be introduced
      into widespread use in practical public health care.

PMID- 9035887
TI  - [The prostacyclin-thromboxane system and bronchial patency in patients with
      pulmonary tuberculosis].
AB  - The paper is concerned with a study in which a contribution was assessed of the
      prostacyclin-thromboxane system to the development of disturbances in bronchial
      patency in patients with pulmonary tuberculosis. It has been established that the
      prostacyclin-thromboxane system has an active part to play in the evolution and
      formation both the pattern of the tuberculous process and ventilatory disorders,
      the most important contribution being made by the proportion
      prostacyclin:thromboxane.

PMID- 9035888
TI  - [The effect of direct x-ray contrast lymphography on pulmonary perfusion
      function].
AB  - Overall twenty-five persons (8 males and 17 females) were enrolled in a study on
      the influence of straight radiopaque lymphography with an oily substance, on the
      condition of pulmonary microcirculation, as evidenced by perfusion
      pulmoscintigraphy. There was a significant decrease in the accumulation of 99m-Tc
      macroaggregate (TCK-8) in lower portions of both lungs 24 hours after the
      lymphography and normal dispersal 10 days after the study made. The authors
      suggest that the radiopaque substance might stimulate the inflammatory processes
      in chronic nonspecific diseases of the lungs.

PMID- 9035889
TI  - [Thrombocyto- and coagulopathies in patients with diabetic glomerulosclerosis and
      chronic glomerulonephritis].

PMID- 9035890
TI  - [The role of autonomous flora in the realization of manifest forms of urinary
      tract infection].
AB  - The investigations done showed that autoflora migrates from the intestinal
      reservoir into different organs and tissues passing through the injured surface,
      urinary tracts. Injury to the tissue structures results in derangement of the
      mechanisms of transmembranous transport, sedimentation of autoflora in the focal
      lesions, with the ensuing clinical manifestation of the illness being readily
      recordable. Location of the focal lesion, share that the autoflora has in the
      inflammatory reaction of the macroorganism, is most important stage-removing the
      injured tissues and subsequent regeneration. It is the immune system that
      controls this process.

PMID- 9035892
TI  - [The acid-base status of chronic alcoholics undergoing a bicycle ergometry test].

PMID- 9035891
TI  - Catecholamine changes in patients with depression under the action of high
      intensity light.
AB  - Preponderance in depression of the melancholy affect was characterized by a drop
      in the level of norepinephrine (NE) and rise in epinephrine (E). Exposure to
      light was associated with fall in E, with no change recordable in NE. In anxious
      depression, following light therapy, high levels of excretion of both
      catecholamines tended to return to normal. Ligh was found to cause opposite
      changes in the quantitative measures depending upon the initial value for the
      E:NE ratio (above or below control).

PMID- 9035894
TI  - [The cytotoxic function of normal leukocytes and in chronic tumorous diseases of
      the blood].

PMID- 9035893
TI  - [The morbidity characteristics of diseases of the bone and muscle systems in
      workers in iron-ore mines and quarries depending on the conditions and nature of
      the work].
AB  - In terms of applying for medical advice in osteomuscular disorders, taking second
      place in the structure, it has been established that in practically identical
      values for the general level of morbidity, the incidence rate of lumbosacral
      radiculites, myalgias and myosites in drifters and drillers is 5.8 and 2.5 times
      as high respectively, that of thoracic and lumbar, cervical osteochondrosis,
      epicondylitis in drivers--3.9, 2.4, and 3.3 times as high, which facts might
      suggest an important role in the etiology of the above conditions, in the first
      place, of great physical loads plus high levels of noise, vibration, cooling
      microclimate, in the former case, and such loads coupled with high nervous and
      emotional tension, general low frequency vibration, noise, in the latter case.
      The established level and structure of occupational disorders of the locomotor
      system in both groups workers suggest their inadequate identification in respect
      of both amount and nosology.

PMID- 9035895
TI  - [The dust factor in the manufacture of basalt fibers].
AB  - A study was made of the labour conditions of those workers engaged in the
      production of basalt fibre (BF). Morphological makeup is examined as is
      dispersity and cytotoxicity of the dust produced in the process of BF making. An
      issue is addressed of usefulness of setting special hygienic regulations for BF
      dust.

PMID- 9035896
TI  - [The effect of viral hepatitis A on thyroid function].
AB  - Blood serum levels of hormones of the thyroid gland (triiodothyronine and
      thyroxin) were studied in adolescent girls with viral hepatitis A (VHA). Revealed
      in this patient population was a marked hormonal dysbalance dependent upon the
      period and severity of the disease course. It is caused by disturbances in
      metabolism of thyroid hormones in the liver as well as by shifts in
      hormonogenesis in iron. The above hormonal indicators may serve as additional
      criteria of gravity and activity of the pathological process in the liver under
      VHA.

PMID- 9035897
TI  - Calgary curriculum on gay and lesbian tissues.

PMID- 9035898
TI  - Curing and killing.

PMID- 9035899
TI  - Death of an Asian immigrant.

PMID- 9035900
TI  - Cardiac beta-adrenoreceptor activation and ventricular fibrillation under normal
      and ischemic conditions.
AB  - OBJECTIVES: To investigate the role of ventricular and atrial beta-adrenoceptor
      activation by isoprenaline in the genesis of rhythm disorders and risk of
      fibrillation in the healthy or ischaemic heart. METHODS: The study was performed
      in anaesthetized, open-chest pigs. Electrical fibrillation threshold (EFT) of the
      ventricles was measured with trains of diastolic stimuli of 100 ms duration
      synchronized with respect to the R-waves and delivered to the myocardium by a
      subepicardial electrode introduced into the area which could be subjected to
      ischaemia. Monophasic action potential (MAP) and effective refractory period
      (ERP) were recorded in the same area. Ischaemia was obtained by complete
      occlusion of the left anterior descending coronary artery near its origin during
      increasing periods (30, 60, 90, 120, 150, 180, 240 s). RESULTS: At a rate varying
      according to the action exerted by isoprenaline on the sinus rate, EFT decreased
      by about 30% in the healthy heart during the infusion of 0.5 micrograms/kg/min
      isoprenaline under the influence of the acceleration of cardiac beats. In the
      ischaemic heart, sinus tachycardia accelerated the fall in EFT and the reduction
      in MAP duration and resulted sooner in spontaneous ventricular fibrillation.
      During ventricular pacing at a constant rate of 200 beats/min, isoprenaline
      raised EFT by nearly 80% in the absence of ischaemia, but this rise was abolished
      by ischaemia, at least of no-flow type. CONCLUSION: Tachycardia produced by
      activation of atrial adrenoceptors decreases EFT in the healthy heart and
      aggravates its fall in the ischaemic heart. Ventricular adrenoceptor activation
      counteracts the EFT fall related to tachycardia in the healthy heart, but not in
      the ischaemic heart. Therefore, the protection against ischaemic fibrillation due
      to beta-blockers would be essentially attributable to their action on the sinus
      nodes.

PMID- 9035901
TI  - Mechanisms of skin irritations.

PMID- 9035902
TI  - Physiologic response of chronically inflamed and accommodated human skin.

PMID- 9035903
TI  - An immunohistochemical study of contact irritant and contact allergic patch
      tests.

PMID- 9035904
TI  - Modulation of integrins on epidermal keratinocytes in vivo and on in vitro
      reconstructed epidermis.

PMID- 9035905
TI  - Human in vivo microdialysis technique can be used to measure cytokines in contact
      reactions.

PMID- 9035906
TI  - The spectrum of irritancy and application of bioengineering techniques.

PMID- 9035907
TI  - Irritant dermatitis: experimental aspects.

PMID- 9035908
TI  - Transepidermal water loss measurements in patch test assessment: the need for
      standardisation.

PMID- 9035909
TI  - Laser Doppler image scanning for assessment of skin irritation.

PMID- 9035910
TI  - Image processing of 20 MHz B-scan recordings of irritant reactions.

PMID- 9035911
TI  - Horny layer thickness as assessed functionally does not predict sodium lauryl
      sulphate skin irritation.

PMID- 9035912
TI  - What can we learn from epidemiological studies on irritant contact dermatitis?

PMID- 9035913
TI  - Occlusion does not influence the repair of the permeability barrier in human
      skin.

PMID- 9035914
TI  - Efficacy of barrier creams.

PMID- 9035915
TI  - Effect of N-acetylcysteine, an inhibitor of tumor necrosis factor, on irritant
      contact dermatitis in the human.

PMID- 9035917
TI  - Quantitative structure-activity relationship and cytotoxicity.

PMID- 9035916
TI  - Topical corticosteroids: experience with mometasone furoate.

PMID- 9035919
TI  - Transcutaneous electrical resistance: application in predicting skin corrosives.

PMID- 9035918
TI  - Measurement of proinflammatory mediator production by cultured keratinocytes.

PMID- 9035921
TI  - Validation of alternative tests in the European Union.

PMID- 9035920
TI  - EEC/COLIPA in vitro photoirritancy program: results of the first stage of
      validation.

PMID- 9035923
TI  - Statistics on occupational dermatoses in Finland.

PMID- 9035922
TI  - Irritant reactions on hairless micropig skin: a model for testing barrier creams?

PMID- 9035924
TI  - Objective and reproducible assessment of irritants in vivo. A reappraisal of the
      IT50 in honour of Kligman and Wooding.

PMID- 9035925
TI  - Irritant contact dermatitis of the hands in housewives.

PMID- 9035926
TI  - Occupational dermatitis in hairdressing apprentices. Early-onset irritant skin
      damage.

PMID- 9035927
TI  - Expression of atopic criteria in a population of medical nurses and hairdressers
      at the beginning of vocational training.

PMID- 9035928
TI  - Identification of high-risk groups for irritant contact dermatitis by
      occupational physicians.

PMID- 9035929
TI  - The long-term prognosis in irritant contact hand dermatitis.

PMID- 9035930
TI  - Metalworking fluid dermatitis: a comparative follow-up study in patients with
      irritant and non-irritant hand dermatitis.

PMID- 9035931
TI  - The occlusive effects of protective gloves on the barrier properties of the
      stratum corneum.

PMID- 9035932
TI  - Papular and follicular contact dermatitis: irritation and/or allergy? Swiss
      Contact Dermatitis Research Group.

PMID- 9035933
TI  - Human barrier formation and reaction to irritation.

PMID- 9035934
TI  - CKS knee prosthesis: biomechanics and clinical results in 42 cases.
AB  - From 1991 to 1993 a total of 42 CKS prostheses were implanted for the following
      reasons: osteoarthrosis (34 cases), rheumatoid arthritis (7 cases) tibial
      necrosis (1 case). At follow-up obtained after 17 to 41 months the results were:
      excellent or good: 41; the only poor result was probably related to excessive
      tension of the posterior cruciate ligament. 94% of the patients reported complete
      regression of pain, 85% was capable of going up and down stairs without support.
      Mean joint flexion was 105 degrees. Radiologically the anatomical axis of the
      knee had a mean valgus of anatomical axis of the knee had a mean valgus of 6
      degrees. The prosthetic components were always cemented. The posterior cruciate
      ligament was removed in 7 knees, so that the prosthesis with "posterior
      stability" was used. The patella was never prosthetized. One patient complained
      of peri-patellar pain two months after surgery which then regressed completely.

PMID- 9035935
TI  - [Maximum surgical management within the scope of extraterritorial deployment of
      the federal army. Current medical service concepts and their realization in
      Croatia/Bosnia-Herzegovina].

PMID- 9035936
TI  - [Equitable fee schedule and organizational leeway of the KVen. Two important
      decisions of the Federal Health Office].

PMID- 9035937
TI  - [New legal developments in employment law].

PMID- 9035938
TI  - [Information via GOA in completing an elective procedure. Decision of the federal
      court 19 December 1995 - III ZR 233/94-].

PMID- 9035939
TI  - [Callus distraction in tibial defect fractures].
AB  - Lower leg fractures with an osseous defect can be treated effectively with the
      callus distraction technique by Bier-Ilizarov. Because osteocytes are cultivated
      at the site of the defect, a real biological system is working-in contrast to
      other methods. Especially in lower leg fractures with a denuded tibia, the
      technique of primary shortening to cover the soft-tissue defect with subsequent
      compensatory lengthening by callus distraction is valuable. This technique does
      not need special hospitals but skillful surgeons. A closed surgeon-patient
      relation ship is required because most treatments are done on an outpatient
      basis. The cosmetic and functional results are good.

PMID- 9035940
TI  - [The monorail system--bone segment transport over unreamed interlocking nails].
AB  - A treatment protocol is demonstrated, consisting of an osteotomy, either proximal
      or distal, of the bone defect with subsequent segmental transport via an
      anteromedially (tibia) or laterally (femur) mounted AO external fixation over an
      unreamed interlocking nail (monorail system). Twenty patients were treated by
      this method with indications as follows: 13 had a segmental bone defect of the
      tibia, 3 of the femur. Three patients showed post-traumatic and postinfectious
      leg-length discrepancies and one was treated for hypertrophic non-union of the
      femur. Defect distance varied between 5 and 18.5 cm and average time for
      transport was 19,42 days/ cm for the tibial shaft, 15,93 days/cm for the femur.
      Two patients developed deep infection, which required change of treatment,
      removing the monorail system and application of an Ilizarov apparatus. Despite
      complications using the monorail system, all patients healed and no amputations
      were required. The monorail system can be used as an alternative to the Ilizarov
      method under certain criteria of patient selection; these criteria are shown by
      an algorithm for segmental bone defects without infection, respecting the soft
      tissue status with or without neurovascular compromise.

PMID- 9035941
TI  - [Plastic soft tissue coverage in defect fractures of the tibia].
AB  - Sequential radical debridement and early soft-tissue reconstruction have
      considerably decreased the amputation rate, length of hospital stay, chronic
      osteitis, the rehabilitation period and secondary reconstructive procedures in
      lower leg injuries. The introduction of distraction osteotomy and "biologic
      osteosynthesis procedures" have led to shorter and safer osteoplastic methods.
      The indication, tactics and technical pitfalls of current interdisciplinary
      treatment options requiring modifications in soft-tissue coverage are presented.

PMID- 9035942
TI  - [Defect fractures of the tibia--various forms of bone replacement].
AB  - Different bone substitutes exist for reconstruction of segmental tibial bone
      defects. The choice of bone substitute is limited by the quality of the
      surrounding tissue and the size of the bone defect. Especially in large bone
      defects, the freely or microvascularly transferred autogenic graft should be
      preferred. Allogenic transplants or artificial bone substitutes, such as spongy
      calcium phosphate materials, are suitable only for implantation in smaller, well
      vascularized bone defects or as an additional procedure in large bone defects. In
      infected cases, allogenic and artificial, especially slowly resorbable implants,
      have to be avoided. The prerequisite for defect reconstruction is stable internal
      fixation.

PMID- 9035943
TI  - [Craniocerebral trauma--new pathophysiologic aspects].
AB  - In the last two decades our understanding of the pathophysiology of severe head
      injury has significantly increased. It has become evident that secondary neuronal
      damage may occur and should be prevented. It is ischemia, similar to that seen
      with stroke and aneurysmal subarachnoid hemorrhage, that causes secondary brain
      damage. Therefore, careful monitoring of blood pressure is indicated, and the
      treatment of arterial hypotension/hypertension should begin as soon as possible.
      Moreover, there are some new pharmacological concepts for changing the threshold
      for ischemia in brain tissue. At the present time, however, valid data concerning
      clinical use are still not available. Therefore, mild hyperventilation and
      sedation during the initial post-traumatic phase and lowering of intracranial
      pressure by osmotherapeutics remain the most important treatment modalities, as
      they were 20 years ago.

PMID- 9035944
TI  - [Routine diagnosis and targeted diagnosis of craniocerebral trauma].
AB  - The basis for aggressive treatment of patients with severe head injuries is swift
      and efficient diagnostic management of trauma victims. The best imaging modality
      for the detection of relevant intracranial injuries is cranial computed
      tomography. The use of CT is also justified from an economic point of view. CT is
      supported by plain X-ray and for special purposes by Doppler sonography, digital
      subtraction angiography and magnetic resonance imaging. Further indications of
      imaging procedures are the evaluation of the time course of intracranial
      injuries, treatment monitoring and the detection of secondary complications.

PMID- 9035945
TI  - [Craniocerebral trauma in acute surgical management. Primary care in a general
      community hospital].
AB  - Head traumas frequently occur in polytrauma patients but are also found as
      isolated injuries. In our hospital trauma center without a neurosurgical
      department, in a 21-month period, 489 patients with head/brain trauma were
      treated. This represents 6.5% of all patients treated in the trauma and
      reconstructive surgery clinic. In commotio cerebri (CC = 89.5% of the patients)
      constant conservative management and an uneventful course were observed; in 69
      patients with contusio cerebri, 18 craniotomy operations had to be performed. In
      contrast, in only two cases was reoperation because of recurrent hematoma
      necessary. In four cases with complex and/or additional injuries, transfer to a
      neurosurgical center took place, and in two cases photophone consultation with
      that center was used. The mortality was 14.5%. The diagnostic and therapeutic
      regimens for the different types of injury and the requirements for the
      management of head/brain trauma in trauma centers without neurosurgical
      departments are presented: emergency service and medical staff, emergency room
      management, intensive care management, qualified neurological examination, X-ray
      imaging, including CT scan, OP-room equipment and trained surgeons. If these
      requirements are not available in a given hospital, early transfer of all
      patients for whom surgical management could be necessary to a neurosurgical
      department should be attempted. Only in patients with severe bleeding must
      immediate craniotomy be performed even in hospitals which do not have all the
      above mentioned facilities. In patients with intracerebral bleeding, bleeding in
      the dorsal fossa, injury of brain nerves, carotid artery or sinus cavernosus
      injuries, frontobasal injuries with liquor fistula or pneumonencephalon, transfer
      of the patients to specialized neurosurgical centers is indicated. With this
      selection, we obtained the same results in a trauma center without a
      neurosurgical department as reported in the literature. This avoids overloading
      neurosurgical centers with head/brain injury patients.

PMID- 9035946
TI  - [Management of craniocerebral trauma in a neurosurgery center].
AB  - Aggressive treatment of patients with severe head injury increases the chance for
      survival and good functional outcome in most cases. To prevent irreversible
      cerebral lesions, the key point of treatment is the management of intracranial
      hypertension caused by intracranial hematomas, brain edema and impaired
      circulation of cerebrospinal fluid (CSF). Therapeutic standards are surgery of
      traumatic hematoma, osmotherapy and mild hyperventilation for brain edema, and
      CSF drainage. In highly elevated intracranial pressure (ICP) administration of
      barbiturates and forced hyperventilation can be considered.

PMID- 9035947
TI  - [What is prevention of perioperative infection? Overview exemplified by trauma
      surgery].
AB  - The prevention of perioperative infection requires an interplay of technical
      equipment, good surgical technique and proper attention to hygiene. The basis for
      this is a well-structured and well-organized department using well-known,
      generally practised routine procedures and solid, realistic time planning. The
      most important technique for supervising and optimizing behaviour (with regard to
      both operative technique and hygiene) is the example of "being there" ("inter
      esse"). In this way, mistakes regarding details are noticed immediately.
      Moreover, the best form of quality control is a long-term, honest survey of
      infection statistics that is managed by one responsible person only. Above all,
      the infection statistics should detect factors predisposing to infection that can
      be modified by everyday staff attention. The protection of staff against
      infection is equally as important as the protection of patients. The question of
      whether routine perioperative antibiotic prophylaxis or treatment in trauma
      surgery is useful under the present conditions has not yet been answered.

PMID- 9035949
TI  - [Retrograde interlocking nailing of distal femoral fractures with the
      intramedullary supracondylar nail].
AB  - Between June 1993 and September 1995, 18 distal femoral fractures were treated
      using the supracondylar intramedullary nail. There were 8 type A fractures and 10
      type C fractures (AO classification). The operative technique involved retrograde
      insertion of an unreamed supracondylar nail through the intercondylar notch.
      Follow-up was available on all patients and averaged 18.3 months (range 6-32
      months). All fractures healed with an average time to union of 12.4 weeks (range
      8-16 weeks). Bone grafting was not necessary in any case. Sixteen patients
      achieved almost the same ROM as they had had before the injury. One patient
      developed a varus malignant and underwent correction with a supracondylar
      osteotomy 20 months post trauma. There were no infections or nonunions. The
      retrograde supracondylar nail is an excellent alternative to plate osteosynthesis
      in the management of dia- and supracondylar femoral fractures.

PMID- 9035948
TI  - [The "low contact plate" for stabilizing the dislocated intra-articular calcaneus
      fractures].
AB  - Open reduction and internal fixation of intraarticular calcaneus fractures have
      been increasingly emphasized in recent years. Operation of most of these
      fractures is via an extended lateral approach. Different implants are used to
      stabilize the often complex fractures. We have developed a low contact plate that
      is specially designed for calcaneal fractures. Because the design is based on the
      anatomy of the calcaneus, all types of fractures can be treated. The plate has a
      large number of holes to accommodate screw fixation. Our results in 36 cases were
      comparable to those of other series using open reduction and internal fixation
      with plates and the demands on the plate were fulfilled.

PMID- 9035950
TI  - [A new score for comparing outcome of surgical management of Achilles tendon
      ruptures].
AB  - From January 1987 to March 1994 three hospitals in the city of Magdeburg treated
      a total of 103 subcutaneous Achilles tendon ruptures operatively. We created a
      special score to compare the outcome of the different operation techniques used.
      Important aspects of the follow-up examination were isokinetic measuring of power
      and staying power by means of a KIN-TREX dynamic measuring device and the
      clinical check-up in comparison with the histological results and the patients'
      history. Degeneration could only be proved histologically in 38,8% of the cases.
      The average score of all OP methods applied was 767 of possible 1000 points. The
      adaptation suture (781 points), Silfverskiold's technique (772 points) and the
      fibrin adhesive technique (754 points) showed approximately the same results. The
      theory that all of the ruptures have a histological degeneration background seems
      to be wrong. Isokinetic measuring can be very helpful in preparing a
      postoperative regimen to find the optimum load.

PMID- 9035951
TI  - [Plastic surgery treatment of extensive decubitus ulcers of the pelvic area].
AB  - Between 1980 and 1995, 207 patients with 219 extensive pelvic pressure sores
      underwent reconstructive surgery at our department. Eighty patients operated upon
      between 1992 and 1995 were followed up. The postoperative complication rate was
      22% and the relapse rate 27%. Pre- and postoperative management has been
      standardized for the purposes of quality control. The value of preoperative
      management, choice of flap, operative procedure and postoperative care are
      discussed in this paper.

PMID- 9035953
TI  - [Current status of treatment of Achilles tendon ruptures. Results of a nationwide
      survey in Germany].
AB  - In a standard questionnaire distributed nationwide, we questioned staff from 1307
      clinics (surgical, trauma-surgical, orthopedic), of which 787 clinics (60.2%)
      answered by letter. In 698 clinics (88.7%), operation is considered the standard
      therapy. Seventy-five clinics (9.5%) use both conservative and operative therapy
      (average postoperative rate of complication 3.5%). Only 14 hospitals (1.8%) treat
      strictly conservatively. The average rate of reruptures is 1.6% in the operated
      group (77.7% postoperative plaster cast fixation) regardless of postoperative
      treatment; the conservative group (96.1% functional treatment) showed 2.7%
      reruptures. Thus, operation is the standard therapy for fresh ruptures of the
      Achilles tendon in Germany. However, there seems to be a trend towards
      conservative functional therapy.

PMID- 9035954
TI  - [The dynamic hip screw with support plate--a reliable osteosynthesis for highly
      unstable "reverse" trochanteric fractures?].
AB  - ORIF management of unstable trochanteric fractures of type A3 of the A0
      classification is difficult because of lateral dislocation of the proximal
      fractured segments, particularly when only the sliding hip-screw is used for
      fixation. A connectable butt-press plate was recently developed in order to
      prevent this type of dislocation. We review the results with this fixation
      technique in 22 elderly patients with an average age of 76 years who presented
      with highly unstable trochanteric fracture of the A3 type. Three patients died of
      diseases unrelated to the trauma or operation before the fractures had healed.
      The other 19 were followed prospectively until fracture healing had occurred.
      Complaints, leg shortening and changes in the CCD angle were recorded.
      Furthermore, the mobility score was determined. Although the patients were able
      to bear full weight after the operation, no lateral dislocation of fragments was
      observed. Only 1 patient had a varus dislocation of 5 degrees until the fracture
      had consolidated. This was due to severe osteopenia and subsequent dislocation of
      the screw within the femoral head. No pseudarthrosis, osteitis or rotational
      malalignment was noted. Five of the surviving patients had a lower mobility score
      after fracture healing as compared to the status before the fracture was
      sustained. On the basis of this review, we recommend the use of this new
      connectable buttress plate with sliding hip screws because it provides sufficient
      fixation of highly unstable fractures of type A3.

PMID- 9035952
TI  - [Ultrasound follow-up of callus distraction of the tibia. Technique,
      possibilities and limits].
AB  - In a prospective study 20 patients were monitored with serial sonograms and
      radiographs during distraction osteogenesis at the lower limb. All sonograms were
      obtained in four planes using a 7.5 MHz transducer. The distraction gap was seen
      as a sonolucent area in all patients after corticotomy. At an average of 20.7 (14
      28) days after the beginning of the distraction, echogenic foci occurred and
      showed increasing longitudinal alignment with further distraction. Radiographical
      signs of beginning mineralization were seen an average of 48.3 days after the
      start of the distraction. Exact measurement of the distraction gap was possible
      in all patients during lengthening. Bone healing complications and hematoma could
      be detected by ultrasound. A rapid increase of bone mineralization was seen after
      the distraction was stopped. With increasing cortication of the regenerate bone,
      sonograms showed a hyper-reflecting solid line so that further mineralization and
      the time of removal of the fixator could not be assessed by ultrasound.
      Ultrasound is more sensitive than radiography in identifying new bone formation
      during distraction, measuring the length of the distraction gap, and detecting
      early bone-healing complications and can therefore reduce the need for
      radiographs.

PMID- 9035955
TI  - [Shockwave treatment of therapy refractory soft tissue pain].
AB  - Extracorporal shock-wave application (ESWA) has been used in the treatment of
      stones located in the kidneys, bile, pancreas and the glandula parotis. In the
      last 2 years several studies have shown the benefit of ESWA in the treatment of
      soft-tissue disorders and tendinosis calcarea. To date, the exact mechanism is
      unknown. Local hyperemia following damage or afferent inhibition is discussed.
      The possibilities and indications of ESWA with respect to several syndromes are
      presented. The results show the benefit of ESWA in the treatment of chronic soft
      tissue disorders without severe side effects. Some patients showed small
      subcutaneous hematomas and erosion of the skin when energies about 20 mJ were
      used. Forty-seven of 84 of the patients obtained complete relief; 24 patients
      showed a marked reduction in their complaints. In only 13 of 84 cases was the
      treatment unsuccessful.

PMID- 9035956
TI  - [Patient specific documentation of complications in trauma surgery. Concept,
      problems and results].
AB  - Quality management requires correct and comprehensive monitoring of all
      complications. Since January 1995 in the department of trauma and orthopaedic
      surgery complications have been recorded immediately when the patient is
      scheduled for reoperation or when complications become evident during the X-ray
      conference or at follow-up clinics. Two senior surgeons note all available
      information on a sheet of paper. Data are completed as soon as possible and
      entered into a PC data base. All cases are followed up by the respective surgeon
      and discussed at monthly complication conferences. A case is not closed until the
      end result has been documented. We discuss the theoretical and practical problems
      of this procedure and present the statistical evaluation for 1995.

PMID- 9035957
TI  - [Impalement injury of the colon, iliac vein and sacrum--a rare combination in
      penetrating abdominal trauma. A case report].
AB  - We report on the treatment of a patient who sustained a penetrating abdominal
      wound with injury of the left common iliac vein, the sigmoid colon and the sacrum
      in a motorbike accident. The left iliac vein injury was treated using a Gore-Tex
      vein patch and an A-V fistula. The colon was restored after an intraoperative
      washout. The punched fragment of the sacrum was removed. An additional fracture
      of the proximal left humerus was managed with an osteosynthesis in a second
      operation. The principles of management of combined colon and vascular injuries
      are discussed and a short review of the literature is given.

PMID- 9035958
TI  - [Reversed musculus biceps femoris flap for covering a defect of the distal
      thigh].
AB  - We report the case of a 30-year-old female patient, who had suffered a grade III
      open femur fracture in a motor vehicle accident 14 weeks prior to being
      transferred to the trauma department of the University Hospital in Bonn. Upon
      admission to our unit, posttraumatic osteitis, an unstable fracture following
      compression plating, and a soft tissue defect of the anterolateral distal thigh
      were discovered. Following removal of the hardware and stabilization of the
      fracture with external fixation, the infection was brought under control. Because
      the patient refused the time-consuming segmental transport utilizing the callus
      distraction technique, local muscle transfer and shortening of the femur were
      carried out. The most lateral of the hamstring muscles, the biceps femoris, was
      used as a distally based muscle flap utilizing a delay technique. With the help
      of a reversed biceps femoris flap, the soft tissue defect was closed, the
      infection subsided and the fracture healed. The surgical technique is outlined.

PMID- 9035959
TI  - [Biocoral--an alternative bone substitute].
AB  - Biocoral is a biomaterial derived from natural corals, and it has surgical
      applications. Since 1992 the author has been using this material as a bone graft
      substitute in maxillofacial surgery. Seventy-seven clinical implantations were
      done for different indications. The results suggest that coral grafts are well
      tolerated and become partially ossified when the calcified skeleton is resorbed.
      This material has been demonstrated to be successful.

PMID- 9035960
TI  - [Elastic intramedullary cavity splint. Comment on the contribution by Hahn et
      al].

PMID- 9035961
TI  - The use of combined FISH/GISH in conjunction with DAPI counterstaining to
      identify chromosomes containing transgene inserts in amphidiploid tobacco.
AB  - We have used combined fluorescent and genomic in situ hybridization (FISH/GISH)
      together with 4',6-diamidino-2-phenylindole (DAPI) counterstaining to determine
      simultaneously the chromosomal integration site and subgenomic allocation of a
      transgene insert in amphidiploid tobacco (Nicotiana tabacum, 2n = 4 chi = 48).
      The procedure provides sufficient information on physical markers to identify at
      least 20 out of 24 chromosome pairs of two tobacco cultivars commonly used in
      studies on transgene expression and silencing (cv. Petit Havana SR1 and cv.
      Gatersleben). The chromosomes can be distinguished on the basis of diploid
      parental ancestry, size, morphology, the presence of rDNA loci and/or
      intergenomic exchanges, and the DAPI banding pattern, which is shown here for the
      first time for N. tabacum. From a single ISH experiment, it should now be
      possible in most cases to identify a tobacco chromosome carrying a transgene
      insert, thus permitting systematic studies of how the chromosomal location of
      transgenes influences expression levels.

PMID- 9035962
TI  - [The history of veterinary medicine at the Georgia Augusta University of
      Gottingen].
AB  - 225 years ago at the university of Gottingen J. C. P. ERXLEBEN has founded
      veterinary medicine as an academic science in Germany. Epochs and changes of this
      discipline at the oldest university veterinary institution in Germany are
      described-exemplified with personalities who represented this scientific field at
      the Georgia Augusta.

PMID- 9035963
TI  - [225 years of the Veterinary Institute--modern research in historic buildings].
AB  - The institute of Veterinary Medicine is the oldest veterinary school of Germany
      and nowadays it is part of the agricultural faculty of the Georg-August
      University of Goettingen. Because of shifts in the emphasis of research in
      veterinary science in the area of animal production and hygiene several
      structural changes have been made over the last few years. In this brief
      introduction latest developments at the institute of Veterinary Medicine are
      reviewed.

PMID- 9035964
TI  - [Recent perceptions about chromosome pairing in meiosis].
AB  - Recent results from meiotic research in animals are presented with emphasis on
      the pairing behaviour of autosomes und sex chromosomes. Synaptonemal complex
      preparations were primarily utilized, that allowed observations of the pairing
      behaviour of the sex chromosomes is quite remarkable. The structure and function
      of the synaptonemal complex is discussed and the localization of the pseudo
      autosomal region on the sex chromosomes is described.

PMID- 9035965
TI  - [Analysis of gene effects on performance characteristics].
AB  - In farm animals, associations between individually identified genotypes and the
      values of performance traits were investigated since more than 30 years. The
      topic of research was largely determined by the Veterinary Institute of the
      University of Gottingen. For the experimental analysis of gene loci, for which
      allelic variants are connected with alterations of trait values, new techniques
      of DNA diagnostic were of crucial significance. Thereby, two approaches of
      analysis of quantitative trait loci (QTL) can be distinguished. By considering
      informative groups of animals, the first approach uses marker loci in order to
      trace the inheritance of their alleles and thus simultaneously the transfer of
      specific chromosome sections to individuals of the offspring generation. By this
      manner, the associations between the marked chromosome regions and trait values
      are calculated. Results are shown for examples from experiments with milk
      performance in cattle and with fatting and carcass traits in pigs. In the second
      approach, genetic effects of trait values are assigned to distinct genes or gene
      clusters. For this purpose, variants of the gene structure are identified and
      then analysed for their effects on the formation of specific trait values. As an
      example of such a functional analysis of single gene positions, the milk protein
      coding genes in cattle are given. From the data we see that DNA techniques allow
      a direct access to genotypic information and so far-reaching potential for
      tracing back effects on trait values to single nucleotide differences. However,
      such a functional analysis need specific test systems which are able to consider
      the complex net work between single gene effects and the multifactorially caused
      values of performance traits. This will be possible by proceedings, which
      identify the gene effects in vivo and the balancing forces of haplotype
      combinations in populations. Genetic parameters of such investigations are needed
      for farm animal populations before variants of genotypes are applied for
      breeding.

PMID- 9035966
TI  - [The intracytoplasmatic spermatozoa injection--the way out of the "male fertility
      crisis"?].
AB  - In contrast to the treatment of female infertility, therapies for male-factor
      subfertility were disappointing in the past. Specific therapeutic choices
      available were limited and patients were treated mostly empirically. However, no
      published results have been able to demonstrate any real benefits from these
      treatments. In 1992 a new procedure of assisted fertilisation was introduced for
      the treatment of severe male subfertility. The successful injection of one
      spermatozoa into an oocyte (intracytoplasmic sperm injection, ICSI) not only
      results in extremely good fertilisation and pregnancy rates but also leads to the
      conclusion that all quality parameters of an ejaculate which have been demanded
      so far are no longer of any value. Fertilisations and pregnancies can be achieved
      by this technique even with motionless spermatozoa, with spermatozoa which have
      not undergone acrosomal reaction, tailless spermatozoa, and morphologically
      aberrant and/or immature spermatozoa.

PMID- 9035967
TI  - [Oral long-term administration of probiotic B. cereus--an alternative for the the
      prevention of enterotoxemia?].
AB  - Aetiology and epizootiology of enterotoxaemia, especially the connection between
      development of the disease and the management of feeding are described and newer
      knowledge about the physiopathology of the disease is presented. A comparative
      description of prophylactic schemes which include immuno- and chemoprophylaxis
      follows. The principles of the application and the effect of probiotic organisms
      as a new approach to prevent the disease are explained. The probiotic effect of
      apathogenic non-haemolysing and non-toxic B. cereus strains which have proven to
      be able to suppress enteropathies and also enterotoxaemia is described.

PMID- 9035968
TI  - [Use of a Coffea arabica tosta extract for the prevention and therapy of
      polyfactorial infectious diseases in newborn calves].
AB  - Two studies have been carried out to evaluate the prophylactic and therapeutical
      effect of a 30%-extract from the coffee-bean seeds Coffeae arabicae on infectious
      diseases in newborn calves. 1. Within a large cattle-herd, which endemically
      showed a high proportion of infections within the gastroenteric and/or
      respiratory systems in calves, a randomised placebo-controlled double-blind study
      has been done. 50 newborn calves were given a subcutaneous injection of 10 ml
      Coffea-preparation 30% on first and third day of life. Another 50 calves received
      physiological saline as control. An index was set up which allowed to daily
      evaluate and compare body-temperature, consistency of feces, exsiccation-degree
      and breathing-rate of the animals. Besides this the number of therapeutical
      interventions and the number of days with disease-symptoms were recorded. Calves
      treated with Coffea-extract showed: on first and second day of life less animals
      with body-temperature below physiological values (p < 0.001 or 0.1 resp.), during
      the first period of diarrhea (between fourth and sixth day) significantly lower
      tendency of diarrhea (p < 0.1; 0.001; 0.005 resp.), after the second period of
      diarrhea (around the 9th day of life) a better and quicker recovery and a lower
      tendency of exsiccation (p < 0.05 on day 10 and 11) as the control-calves.
      Besides this the average duration of illness was shorter (4.7 instead of 7 days)
      and the average number of therapeutical interventions were less (3.1 instead of
      4.5) than in control-calves. 2. Within four cattle-herds endemically showing a
      high rate of diarrhea in newborn calves the morbidity in a total of 371 animals
      could be dropped from about 45% to 10% by prophylactic administration of one to
      three s.-c.-injections of 10 ml Coffea-preparation together with one or two
      million i.U.Vit.A. one time perorally. For prophylactic use two injections of
      coffea preparation. on day 1 and 4 of life proved to be efficient under the given
      circumstances. Therapeutically the daily administration of a combination of
      Coffea-extract together with oral drugs containing tannic substances and diet
      feed could reduce the mortality in animals with acute disease to about 30%.

PMID- 9035969
TI  - [Structure and expression of the porcine skeletal muscle ryanodine receptor
      gene].
AB  - The ryanodine receptors (RYR) are a family of intracellular Ca2+ release channels
      that were first identified in the terminal cistenae of the sarcoplasmic reticulum
      of the skeletal and cardiac muscle. Mutations within the skeletal muscle isoform
      were shown to cause malignant hyperthermia in swine and man. We have analysed the
      genomic structure of the porcine skeletal muscle ryanodine receptor and its
      expression using chimeric reporter gene constructs consisting of the RYR1 gene
      promoter and the chloramphenicol acetyltransferase gene after transfection in
      muscle and non-muscle cells.

PMID- 9035970
TI  - [Proacrosin and acrosin--retrospect of a multifunctional complex].
AB  - Proacrosin is a molecule that is located under the acrosomal cap and that acts as
      a secondary ligand after acrosome reaction. Proacrosin is thought to bind to ZP2
      (zona pellucida receptor 2). The high affinity is based on the interaction of the
      zona pellucida glycoprotein's acidic sulphate groups with basic, positively
      charged amino acids of the proacrosin molecule. Proacrosin is a serine protease
      and is capable to lyse the zona pellucida locally. Our structural analysis of
      proacrosin shows, that the catalytic centre is surrounded by loops containing
      positively charged amino acids which create the binding domain. This review is
      intended to describe the results that lead to the elucidation of the biochemistry
      of proacrosin.

PMID- 9035971
TI  - [The role of proteolipid proteins in the development of congenital tremors type
      AIII: a review].
AB  - During the sixties a sex-specific, hereditary form of congenital tremor type A
      (CT A) appeared which was classified as CT AIII. The symptoms were the same as in
      other subtypes and only autopsy and differential diagnosis showed the distinctive
      signs of this disease. Pigs suffering from CT AIII fail to develop a tight myelin
      sheath and contain a reduced number of oligodendrocytes in their CNS whereas no
      pathological changes can be detected in the PNS. The same symptoms as with CT
      AIII appear in various disorders in animals and humans. The cause for jimpy in
      mice was traced back to a mutation in the PLP gene. In the course of these
      findings different mutations in the human PLP gene were identified and shown to
      be the reason for the rare Pelizaeus-Merzbacher-Disease and the spastic
      paraplegia type 2. If one considers the clinical and histological similarities
      between PLP mutants and CT AIII in pigs it is reasonable to assume that this X
      linked gene plays a major role in the development of CT AIII. In the following we
      describe the isolation and characterization of the porcine PLP gene and its
      possible involvement in congenital tremor type AIII.

PMID- 9035973
TI  - [The problem of breeding for fertility].
AB  - The reproductive success in domestic animals is an important factor towards the
      economical production of livestock. Thus, a lot of energy has been spent on the
      amelioration of the reproduction by means of genetics but no considerable success
      was achieved since the additive genetic variance is low. This communication is
      supposed to elucidate its molecular biological basis in reproduction and
      furthermore, the article should point out the way in research how to improve
      reproductive parameters. We propose to characterize all sorts of genes and their
      gene products that are involved in reproduction. This is to realize a full
      understanding of the sperm egg interaction and to derive benefit from effects
      like heterosis.

PMID- 9035972
TI  - [Muscle specific gene expression during embryonal development].
AB  - The myogenic bHLH-proteins play a crucial role in the determination and tissue
      specific gene expression in skeletal muscle. Being able to regulate themselves
      and the other members of their family they establish the myogenic lineage in the
      precursor cells of the skeletal muscle. The precise mechanisms that lead to the
      manifestation of myogenic cells in vivo are still unknown, but much has been
      learned from the behaviour of established cell lines and targeted mutations in
      the myogenic regulatory factors (MRFs). This review will focus on the results of
      these experiments and outline the major regulatory pathways which lead to the
      formation of skeletal muscle cells.

PMID- 9035974
TI  - [Avian yolk antibodies in diagnosis and research].
AB  - Hens were immunized with bacterial polysaccharide (alginate), Hepatitis B surface
      antigen (HBsAg), and potato viruses (PVA, PVS, PVM, PVX, and PVY). The antibodies
      were isolated noninvasively from the yolks of laid eggs. The purified yolk
      immunoglobulins (IgY) were tested in an array of various assays and diagnostic
      techniques. The methods employed were precipitation reactions, immun
      electrophoresis, ELISA (after biotinylation of IgY), immuno-gold electron
      microscopy, and western and immuno blotting. Some of these methods had to be
      modified according to the special requirements of avian antibodies. The special
      handling of this animal system is described in regard to antibody production. The
      results demonstrate that IgY derived from hens can replace IgG produced by
      traditional methods in mammals. The advantages of this alternate animal system
      are emphasized in respect to animal care, high productivity, and special
      suitability of avian antibodies for certain diagnostic purposes.

PMID- 9035975
TI  - [The diagnosis of liver diseases in the dog].
AB  - This article shows the possibilities of liver diagnosis in dogs. After a short
      introduction about metabolism with some aspects in pathophysiology follows the
      way of investigation from anamnesis, clinical examination, blood work and
      urinalysis to ultrasound, x-ray and biopsy.

PMID- 9035976
TI  - [Anorectal causes of constipation problems in dogs].
AB  - This survey shows the most popular reasons for problems of defaecation in dogs.
      Beyond the pathogenesis, diagnosis and therapy will be discussed.

PMID- 9035977
TI  - [The effect of vitamin A and beta-carotene on the vitamin E status, ejaculation
      parameters and health of boar used for insemination].
AB  - In this study consequences of vitamin A-supplementation to the vitamin E-status
      was investigated in the boar. Three groups of boars, each with 9 animals were fed
      over a period of seven month with 30000 I.E. Vit. A/kg concentrate (group A), 90
      mg b-carotene + 1000 I.E. Vit. A/kg (group B) and 1000 I.E. Vit. A/kg (group C).
      Every boar was given 100 mg Vit. E/kg plus 50 ml soybean oil/kg to induce
      oxidative stress. After four month group C showed a higher amount of tocopherol
      in serum (p < 0.05). The amount of tocopherol in serum of the group B were
      exactly between group A and C. The amount of retinol in serum of the group C
      began to decrease after three month due to the high reserve capacity of the liver
      (p < 0.01). The retinyl ester in serum reflected the state of supply. 90 mg b
      carotene led to an efficiency of 15000 I.E. Vit. A. The vitamin antagonism
      between Vit. A and Vit. E is not based on an antagonism of the intestinal
      resorption. There was no influence on the daily sperm production caused by
      different supplementations. The sperm quality was lowered in group C; the number
      of defective sperm increased (p < 0.001). The supplementation of soybean oil lead
      to an increase of the saturated fatty acids in the fatty acid pattern of the
      sperm cells. The increase of saturated fatty acids was the lowest in group C that
      showed the highest amount of tocopherol in serum.

PMID- 9035978
TI  - [The epidemiology of helicobacteriosis in humans; studies of the survival
      capacity of the microbe in food].
AB  - In man suffering from diseases of the stomach and the duodenum (gastritis, ulcus,
      enteritis, neoplasms), Helicobacter pylori (H..pylori) is frequently detected in
      the mucous membrane of the stomach. Up to now the spread of this agent is not
      quite clear. Since the direct transmission in humans can be taken for granted,
      the following study was to find out whether and for how long the agent mentioned
      above is able to survive in selected food and whether an infection of the
      consumer by these contaminated food is possible. 376 samples of secretions from
      the udder of healthy cows and those with mastitis where tested for the presence
      of H. pylori along with 100 stomachs of chicken from different flocks. In no case
      H. pylori could be detected. H. pylori was inoculated in high concentrations into
      milk and some milk-products. From cooled milk samples the agent could still be
      reisolated after six days in a density up to 10(3) CFU/ml of milk. At room
      temperature or 37 degrees C resp. the pathogen could be detected in milk for
      three to four days only. In yoghurt the agent kept viable for three hours only,
      whereas in kefir for 24 hours. Mean survival time of then hours was found in pH
      neutral curd cheese. The incubation of H.pylori in sterile drip from chicken and
      in physiologic saline resulted in maximal survival time of at least 48 hours at
      room temperature. But in H.pylori-broth the number of microorganisms had dropped
      below the limit of detectability only after 72 hours. At refrigerator-temperature
      (7 degrees C) H. pylori could still be detected within these three media after 72
      hours in high concentrations. In drip from chicken kept at-20 degrees C before
      thawing H. pylori showed a considerable survival time. After four weeks its
      number had only dropped by one to two log cycles, whereas in saline and in broth
      the agent could not be detected anymore after one week at the most. Experiments
      concerning tenacity showed: On culture-media with different pH-values the growth
      optimum of H. pylori was between pH 6.1 and 7.3 H. pylori was suspended in
      melting water from chicken and brought in thin layers onto wooden board, plastic
      and ceramic tiles. The bacterium could be recultured from these surfaces only as
      long as these were moist. At room-temperature the bacterium could not be detected
      anymore on wood after 30 minutes, on plastic or ceramic tiles after 90 minutes.
      At refrigerator-temperature the administered suspensions dried more slowly, so
      that H. pylori survived longer, but it still could not be isolated anymore on
      wood after 240 minutes, on plastic or ceramic tiles after 300 minutes. The
      decimal reduction-time for H. pylori suspensions in broth were. 72 sec. at +50
      degrees C 43 sec. at +52 degrees C 20 sec. at +55 degrees C 10 sec. at +57
      degrees C 4 sec. at +60 degrees C from which data z = 7.9 +/- 0.01 degrees C can
      be calculated. From these experiments on can conclude, that in all probability
      fresh milk and chicken do not contain H. pylori and thus do not represent a
      source of infection for man. After contamination of slaughtered chicken within
      the abattoir or from milk and milk-products within dairy industry by insufficient
      hygiene-management of infected personnel it can not be excluded, that H. pylori
      gets into households by these foods. An infection of the consumer by this route
      is not very likely, but can not be excluded with complete certainly.

PMID- 9035979
TI  - [From transitory insomnia to chronic insomnia].

PMID- 9035980
TI  - [Strategies for coping in schizophrenia].
AB  - Few studies have documented how schizophrenic patients perceived their needs and
      which coping skills they have spontaneously developed. All 48 patients of the
      Louis-H. Lafontaine Young Adults Clinic, a specialised schizophrenia clinic in
      Montreal, were invited to complete the Task Motivation and Problem Appraisal in
      Long Term Psychiatric Patients questionnaire. Our study utilised a descriptive
      approach and a classification of patient's reported problems and their coping
      skills. A panel of researchers and clinical staff then regrouped patient's
      perceived problems into four categories: symptoms, coping strategies,
      organisation of daily activities and interpersonal contacts. The main coping
      strategies utilised by these young patients are confrontation (52%) emotion
      centered coping (57%). Clinical applications can be drawn from paying attention
      to the reports of schizophrenic patients. For example, rehabilitation activities
      can be developed which cater to their perceived needs. Because of frontal lobe
      hypoactivity, which make cognitive appreciation more difficult, their coping
      strategies should be diversified. Patients suffering from negative symptoms of
      schizophrenia mainly attempt to modify emotional impact, until they have
      discovered a way of confronting deficit symptoms. Better motivation to
      therapeutic programmes would result from paying attention to their perspectives.

PMID- 9035981
TI  - [Clinical aspects of obsessive-compulsive syndromes: results of phase 2 of a
      large French survey].
AB  - Obsessive-Compulsive Disorder (OCD) had received a new interest from fundamental
      research (psychopharmacology, neurobiology and brain imagery...). Although more
      investigation of OCD clinical aspects are needed, especially in large cohorts of
      patients, not seen nor investigated only in high specialized psychiatric units. A
      large french survey "Screening-Understanding-Treating OCD" was conducted in 1994
      with the participation of 240 psychiatrists. The survey had included 4,363 new
      consecutive patients consulting in out-patient psychiatry. The phase 1 had shown
      a point prevalence rates of 9.2% for OCD (full criteria of DSM III-R) and 17% for
      OCS (Obsessive-Compulsive Syndromes). From 731 patients, the phrase 2 was
      conducted on a cohort of 646 patients with OCD or OCS and had explored in details
      in the clinical aspects of the OC illness (typology, symptomatic categories,
      comorbidity, OCD spectrum, psychiatric family history and treatment history...).
      The results of the french survey phase 2 had confirmed a variety of classical and
      current literature data, especially: the ICD 10 proposal for diagnostic sub
      typology according to symptomatic predominance (obsessions, compulsions or both);
      the symptomatic clustering of obsessions and compulsions into three major
      categories, suggested by a recent study from the Boston University; the high rate
      of comorbidity with anxiety and depressive disorders and with disorders related
      to the large OCD spectrum (somatoform disorders, eating disorders, impulse
      control disorders, compulsive buying...); the impact of clinical parameters (as
      slowness, avoidance, lack of insight) on clinical global OCD and OCS severity;
      the high rate of intrafamilial psychiatric morbidity (OCD, depression, anxiety
      disorders).

PMID- 9035982
TI  - [Effects of co-administration of an antidepressant and an anxiolytic drug in the
      "learned helplessness" paradigm: importance of hydroxyzine].
AB  - Whereas benzodiazepines are routinely coadministered with tricyclic
      antidepressants, in patients undergoing treatment for depressive disorders,
      little information is known about the combination of benzodiazepines with other
      antidepressants such as specific serotonin reuptake inhibitors (SSRI's), and
      combination with other anxiolytic drugs. On the other hand, it is known that
      benzodiazepines decrease the serotoninergic transmission. The present study was
      undertaken to evaluate the effect of concomittant administration of anxiolytic
      drugs such as benzodiazepines (diazepam, lorazepam) or diphenylmethane derivative
      (hydroxyzine) with specific serotonin reuptake inhibitors, (fluvoxamine,
      fluoxetine, indalpine) on the ability of antidepressant drugs to reverse helpless
      behavior in this test. Our results show that: daily injection of diazepam (0.25-2
      mg/kg), lorazepam (0.06-0.25 mg/kg) or hydroxyzine (8.32 mg/kg) failed to reverse
      the behavioral deficit in rat. In contrast fluvoxamine: 4 mg/kg/day; fluoxetine:
      4 mg/kg/day; indalpine: 1 mg/kg/day significantly reverse the helpless behavior
      in this test; the reversal of helpless behavior by fluvoxamine or indalpine was
      dose-dependently antagonized by daily coadministration of diazepam or lorazepam;
      in contrast, the reversal of helpless behavior by fluvoxamine or fluoxetine was
      not modified by daily coadministration of hydroxyzine (8 mg/kg). In conclusion,
      it may be suggested that combined benzodiazepine-specific serotonin reuptake
      inhibitors, should be avoided. We suggest that anxiolytic drugs such as
      hydroxyzine might be better in coadministration with antidepressants,
      particularly with specific serotonin reuptake inhibitors.

PMID- 9035983
TI  - [Efficacy of zuclopenthixol acetate on psychotic anxiety evaluated in an open
      study].
AB  - The first scale evaluating psychotic anxiety specifically is the "Psychotic
      Anxiety Scale": PAS was proposed and validated by O. Blin et al. in 1988.
      Zuclopenthixol acetate formulation is a both rapid and middle prolonged (2-3
      days) acting neuroleptic used to start the treatment in an acute episode of the
      psychotic illness. It has been established as an effective drug for a broad
      spectrum of symptoms in schizophrenia and other psychosis, but its "angolytic"
      effect had never been quantified. It was interesting to study the efficacy of
      zuclopenthixol acetate on psychotic anxiety with PAS during the first 9 days of
      hospitalisation of psychotic patients. During the study, the clinical evaluation
      was made with the Psychotic Anxiety Scale (PAS) for the main criteria; Clinical
      Global Impression (CGI) and the Nordic side effect scale (UKU) for the secondary
      criteria. Assessments were performed at days, 0, 1, 3, 4, 6, 7 and 9.
      Zuclopenthixol acetate was administered at Day 0, Day 3, and Day 6. Protocol
      allowed an additional injection at D1 in case of insufficient efficacy. Forty six
      patients were included into this open non comparative multicenter study: 23
      patients were male and 23 female. Their mean age (X +/- S) was 32 +/- 10 years,
      and according to DSM III-R, 28 of them got schizophrenia diagnosis, 13 suffered
      from brief psychotic disorder and 3 from schizophreniform disorder (diagnosis was
      missing for two subjects). The mean dosage of zuclopenthixol acetate by
      injection, foreseen in the protocol, was between 126 to 138 mg. Four patients
      were treated with high dose: more than 800 mg during the 9 days of the study and
      6 patients had 5 injections or more. Between D0 and D9, the total PAS score
      decreased from 63 (from moderated to severe anxiety) to 25 (absence of anxiety)
      and the reduction of score was statistically significant from 24 hours after the
      first injection (p < 0.01). Various items analysis of PAS has showed a
      statistically significant reduction from 24 hours for all items (p < 0.01) except
      for physical depersonalisation, inhibition of thought and motor inhibition.
      Assessment index of therapeutic effect (CGI 2) decreased in a statistically
      significant way from 72 hours (p = 0.01). Globally, we found a good correlation
      between Clinical Global Impression and PAS, it was maximal and significant at day
      7 (r = 0.87). According to the UKU scale and the investigators, the treatment was
      well tolerated. The results suggest that zuclopenthixol acetate is an effective
      and reliable way to initiate neuroleptic treatment with an statistically
      significant activity in psychotic anxiety from 24 hours.

PMID- 9035984
TI  - [Clinical effects of clozapine: effect on negative symptoms].
AB  - OBJECTIVES: we have realized an open study in a population of chronic
      schizophrenic inpatients treated with clozapine. The purpose of this study was to
      investigate the clinical response and the effect of extrapyramidal symptoms of
      this atypical antipsychotic. METHODS: our sample is composed of 25 chronic
      hospitalized schizophrenics (18 males, 7 females; average age = 36.57, SD = 8.41)
      with an initial important symptomatology (average score on BPRS = 64.92, SD =
      7.99). The weekly assessment was done using PANSS and EPRS during 9 weeks. After
      a 15-days period of treatment adjustment, each patient reached a daily dose of
      400 mg. Then the dosage was adjusted according to the clinical condition of the
      patients (average = 429.41 mg per day). RESULTS: using the PANSS, we identified a
      statistically significant (p < 0.05) clinical improvement from the fourth week of
      treatment for global score, positive, negative and general psychopathology sub
      score. For EPRS a dramatic improvement (p < 0.01) occurred from the second week.
      We found no correlation between the improvement of negative symptoms and the
      improvement of extrapyramidal symptoms. We individualized a sub-group of 7 good
      responders who showed an improvement of 20% or more on PANSS global score at the
      ninth week. This group showed a statistically significant (p < 0.01) more intense
      initial negative symptomatology compared to non-responders. CONCLUSION: the
      improvement of extrapyramidal symptoms precede the improvement of psychotic
      symptoms; this effect underlines the good neurological tolerance of clozapine.
      The clinical efficacy concerns both positive and negative symptoms. The efficacy
      on negative symptoms seems to be primary. In our sample, patients with intense
      negative symptomatology improve more than others.

PMID- 9035985
TI  - [Alternating addictions: apropos of 3 cases].
AB  - The concept of addiction is now of interest in psychiatry, but is a great subject
      of controversies. It is now recognized that as different disorders as alcoholism,
      drug addiction, bulimia, kleptomania, trichotillomania, pathological gambling are
      to be considered as addictive states. Other pathological behaviours could be
      included in the addictive spectrum (i.e. suicidal behaviours, compulsive
      spending). The comorbidity rates of these disorder are elevated in these
      populations. For example, high comorbidity rates are found between kleptomania
      and bulimia or drug addiction and pathological gambling. Polyaddictive states are
      well established. For some subjects, more than one addiction is present in life
      time, but not occurring in the same period. We present three patients in whom
      different addictive states occurred alternately. All the patients had a history
      of compulsive spending and kleptomania, two of them had a history of bulimia and
      sexual compulsion. Some clinical characteristics were common: recurrent mood
      disorder, depression preceeding the addictive state, no psychoactive substance
      disorder. In all patients, severity of depressive state decreased when addiction
      appeared. Depressive symptoms varied inversely to addiction severity. The
      hypothesis about psychopathological links between kleptomania and bulimia on one
      hand and mood disorders on the other hand has been known for a long time.
      Kleptomania as other impulsive disorders is, for some authors, understood in the
      meaning of a "spectrum affective disorder". For these three patients, an
      antidepressant effect of the behavioural addictions is suggested. In fact, the
      addictions appeared alternately. The possibility of common psychopathological
      and/or biological mechanisms for behavioural addiction is supported by these
      clinical observations, that could contribute to the addiction concept validity.

PMID- 9035986
TI  - [Administration of high dose haloperidol in a patient refractory to treatment
      with traditional and atypical neuroleptics].

PMID- 9035987
TI  - [Detection of anhedonia in the normal subject. Determination of the validity of
      the Chapman and Chapman (1978) revised Physical Anhedonia Scale].

PMID- 9035988
TI  - [Depressive disorders and public health: a review of the economic impact].
AB  - Budgetary control policies implemented in order to cope with the increase in
      health costs in industrialized countries and with the desequilibrium of the
      national health insurance accounts, give rise to the problem of preserving the
      quality of care and quality of life of the patients. Only health economic
      studies, evaluating the possible different therapeutic strategies, will enable us
      to reconcile the 2 terms of the equation whose contradiction might be only
      apparent. This is particularly true for the treatment of psychiatric diseases,
      and especially depression. Budgetary control cannot be reduced to a simple
      management of penury, since the cheapest treatments are not necessarily the most
      profitable. In this context, new strategies are proposed: it is suggested that
      thorough diagnosis (avoiding both the non acknowledgement of the illness and the
      overconsumption of antidepressants) and early optimal treatment, of adequate
      duration, of the depressive disorders might be the most economic attitude in the
      management of this pathology. On the other hand, the impact of the treatment of
      depression on the quality of life of the patient has a direct effect on costs if
      one considers the supplement to medical consumption and the social deficit
      induced by therapeutic failure. It remains that the evaluation of the health
      economics of depression is difficult because of the complexity of the parameters
      involved. Though rather well developed in the UK and in North America, this
      evaluation still has to be introduced in France.

PMID- 9035989
TI  - [Patient education about neuroleptic treatment, can it reduce costs? A pilot
      study].
AB  - Costs generated by chronically mentally ill are very high. Concerning direct
      costs (hospitalisations, outpatient services, medications), they are estimated
      from 120,000 to 160,000 french francs per year. Indirect costs (social security,
      gain lost) are assessed as being at least three times more than direct costs.
      Trimestrial costs, charged to insurance, of the first fourteen patients who
      followed the UCLA medication management module, have been retrospectively
      calculated on the base of the number of consultations, days at the hospital and
      community day center during the previous and following year of the introduction
      of the program. The intervention lasts 3 months with two weekly sessions of 1 h
      30. The medication module aims the following goals: 1) Obtaining information
      about antipsychotic medication; 2) Knowing correct self-administration and
      evaluation of medication; 3) Identifying side effects of medication; and 4)
      Negotiating medication issues with health-care providers. The mean trimestrial
      costs curve goes down following the application of the program and this reduction
      continues 9 months after the end of the intervention. The small numbers of
      patients and the absence of control group do not allow to draw conclusions about
      these results. However, these data provide support to formulate an hypothesis
      about the effect of the module on medication compliance.

PMID- 9035990
TI  - [The elderly, sleep habits and use of psychotropic drugs by the French
      population].
AB  - The aging population in western countries and the increase in longevity make the
      problem of recognition and treatment of sleep disorders more acute in the elderly
      population. The risk of evolution of sleep disorders in the elderly leads to a
      greater weakness of their physical health, a greater dependence on their
      environment, and finally to more frequent recourse to institutionalization. We
      investigated sleep habits, sleep disorders and psychiatric diagnoses, physical
      illnesses and psychotropic drug consumption in a representative sample of the
      general population of France. Interviews were performed over the telephone by lay
      interviews using the Eval Knowledge Based System, a computerized system that
      guides the interviewer through the interview process, 6966 subjects were
      contacted, and 5622 interviews (80.8% of the potential sample) were completed.
      The sample was divided into four age groups: 15 to 44 years old (56.4%); 45 to 64
      years old (25.6%); 65 to 74 years old (10.8%) and 75 years old or more (7.2%).
      Earlier bedtime, long sleep latency, spending more time in bed with a reduction
      of nocturnal sleep time, nocturnal awakenings and daytime naps were found more
      frequently in "young old" (65 to 75 years old) and "old old" subjects (75 years
      old or more). Daytime naps and spending more time in bed with a reduction of
      nocturnal sleep time also distinguished "old old" subjects from "young old"
      subjects. About half of "old old" subjects who complained about their sleep did
      not get a diagnosis of sleep disorder, nor psychiatric disorder (52.4%). An
      insomnia diagnosis was given in 14% of cases (mostly primary insomnia-6.7%) and a
      psychiatric diagnosis in 33.4% of cases (mostly anxiety diagnoses-28.2%). The
      rate of psychotropic drug consumption was 11.7% (95% Cl: 10.9% to 12.5%) for the
      entire sample. This consumption dramatically increased with age: 4.8% between 15
      to 44 years old; 15.6% between 45 to 64 years old; 24.3% in "young old" subjects
      and 32.8% in "old old" subjects. Psychotropic drug consumption was distributed as
      follows: 6.4% of the sample used anxiolytic, 2.7% hypnotic, 1.5% antidepressant
      and 0.9% hypnotic and anxiolytic together. The chronic use (at least one year) of
      hypnotic or anxiolytic drugs was frequent in "old old" subjects (92.6% and 80.2%,
      respectively) and "young old" subjects (74% and 78% respectively). The assessment
      of sleep by the physician should be made part of the routine clinical examination
      of older subjects. Review of the etiology of insomnia complaints is crucial in
      the choice of treatment. The reflex of psychotropic prescription in case of poor
      sleep is neither sufficient nor desirable, especially because of the risk of
      chronic use of the prescription. These data underline the importance of educating
      physicians about consequences of long-term utilization of these drugs and on the
      need for sleep hygiene measures as alternative solutions for treating insomnia
      complaints.

PMID- 9035991
TI  - [Clinical characteristics of chronic schizophrenic patients presenting with
      severe anhedonia].
AB  - The aim of the present study is first to test the existence of a sub-group of
      chronic schizophrenics characterized by a severe anhedonia and secondly to
      determine the characteristics of that sub-group. 150 patients meet the DSM III-R
      and RDC criteria for chronic schizophrenia and 151 healthy subjects constituted
      the control group. The subjects filled out the Physical Anhedonia Scale of
      Chapman (PAS), the Fawcett Clark Pleasure Capacity Scale-Physical Pleasure (FCPCS
      PP) and the abridged form of the Beck Depression Inventory (BDI). The
      distributions of the PAS and FCPCS-PP were studied using a test of normality. In
      the normal group the distributions of the anhedonia scales were unimodal and in
      the schizophrenic group the distributions were not. The schizophrenics were
      dichotomized into anhedonic schizophrenics (PAS scores higher or equal to 29) and
      hedonic schizophrenics (PAS scores lower than 29) and these subgroups were
      compared on socio-clinical variables and PANSS, BPRS and BDI scores using chi 2
      square tests or Mann and Whitney tests. They were 32 subjects in the anhedonic
      sub-group and 128 subjects in the hedonic sub-group. They were not significant
      differences between the sub-groups concerning the sex-ratio, educative level,
      age, mean duration of the illness, mean number of hospitalization and the mean
      dose of antipsychotics. The proportions of depressive and deficit syndromes did
      not differ between the two sub-groups but the proportion of "negatives" (using
      the composite score of the PANSS) was greater in the anhedonic sub-group. A
      discriminant analysis has been done on the items of the BPRS, PANSS and BDI and
      the results have shown that the anhedonic schizophrenics had more hallucinatory
      behavior, disorientation, blunted affect, social withdrawal, cognitive
      distorsions and less anxiety and displeasure than hedonic schizophrenics. Our
      results allow to identify a sub-group of chronic schizophrenia characterized by a
      severe anhedonia and will be confirmed by others studies using prospective
      methodology.

PMID- 9035992
TI  - [Descriptive studies of the use of the Addiction Severity Index in France].
AB  - The Addiction Severity Index (ASI) is an instrument that provides, in a 45
      minutes semi-structured interview, a multidimensional assessment of substance
      abuse patients. It was designed in 1980 by A.T. McLellan et al., from
      Philadelphia PA, in North-America and introduced in France by our group in 1990.
      Over the past five years we have used it in different substance abuse populations
      including alcohol users. The goal of this paper is to review the adaptation
      procedure into French context and to present ASI data from different substance
      abuse sub-groups: opioid dependent subjects seeking treatment and former heroin
      addicted patients in maintenance treatment. After description of the ASI,
      presentation of the training procedure for its optimized use and methodological
      issues, we present for each opiate dependent group acceptability data, results of
      some of the ASI's 240 items and the severity scores. The Addiction Severity Index
      provides assessment of problem severity in seven functional areas in which
      substance abusers are commonly impaired and unable assessment of need for
      treatment. Objective and subjective patient data are collected in the following
      seven areas: medical, employment/ support, alcohol, drug use, legal,
      family/social relationship, and psychiatric. The ASI is both broad in the extent
      of its evaluation and yet easy to use for appropriately trained interviewers. Use
      of the ASI over the past five years allows us to underline the following
      characteristics: in the clinical setting the ASI unable a common descriptive
      analysis for need and adaptation for treatment of different patients populations;
      in the research setting the ASI is particularly suited for epidemiological
      studies of addiction and description, analysis or evaluation research.

PMID- 9035993
TI  - [Suicide mortality in Rhone-Alpes psychiatric sectors. Or the difficulties in a
      study].
AB  - Mandated by the Social Welfare and Health Regional Office, the Regional Health
      Observatory realized a study on mortality by suicide in the psychiatric sectors.
      This work is based mainly on the definitions of a new map of the psychiatry, set
      on June 1994. Its objective was to give to each sector team a set of quantitative
      data on deaths due to suicide, happened on their area, both in term of progress
      (1982-1989) and of comparison (respective level of each sector compared to the
      "departement" mean). This descriptive study is based on the regional cumulated
      mortality data from 1981-1983 and 1988-1990, given by the National Institute of
      Health and Medical Research (INSERM) and on the data of General population census
      in 1990. Epidemiological studies on suicide generally get as reference a
      delimitated geographical basis, accordingly to most of the important statistical
      databanks (nation wide, region wide...). The general psychiatric sectors are
      quite different, as the repartition is complex and their number is important
      (more than 80 for Rhone-Alpes Region) as well as the diversity of local needs and
      the organization in psychiatry. This repartition, responding to the needs of a
      medical and preventive practice, causes a great number of difficulties when one
      tries to approach this reality with statistics: the frontiers between sectors are
      determined with a degree of precision overtaking the one of demographical and
      epidemiological data sources. Taking into account the small size of the sectors,
      the number of deaths by suicide (mean of 10 to 20 by sector) does'nt enable to
      estimate the significance of the results. Despite the difficulty of different
      limitations, the data show inter-sectorial particularities, which could justify a
      regular epidemiologic survey (i.e.g., a growth in number of death by suicide in
      the "departement" of Rhone between 1982 and 1989 is to be noticed more in urban
      areas). Such monitoring suggests a better acknowledgment of the feasibility of
      statistical surveys based on the sectors, and its use in the map of psychiatric
      services as well as the implementation of means, allowing data to be release
      quickly at the local level.

PMID- 9035994
TI  - [Manic-depressive psychoses in adolescence. Influence of life change events.
      Study of family dynamics].
AB  - A sample of 38 adolescents hospitalized for a major depressive episode
      melancholic type or a manic episode during the course of a bipolar disorder
      (according to the DSM III-R Criteria) was examined with particular emphasis on
      precipating life events and family relationships. Psychosocial stressors in the
      year preceding onset of the affective disorder were found in a very high
      proportion of cases (about 80%). Stressors are most often severe. All of these
      stressors have to do with loss or threat of loss, particularly the most frequent
      one: the sentimental failure. Analyzing results of a familial dynamic
      questionnaire, we showed in the MDD sample the prevalence of two
      psychopathological index: maternal rejection, parental dysharmony.

PMID- 9035995
TI  - [Meta-analysis of therapeutic trials: applications in psychiatry].
AB  - Meta-analysis is being increasingly used in therapeutic and clinical research to
      synthetize data from terminated clinical trials. Meta-analysis provides a
      powerful tool to objectively combine data in a quantitative manner, unlike the
      classical general review of literature, which is qualitative and subjective by
      definition, and thus not reproducible, and also the simple data pooling, methods
      which neglects the statistical heterogeneity between studies. The two most known
      objectives of meta-analysis are, to provide an objective decision when the trial
      results have produced contradictory or non-significant results, and to give a
      better estimation of the magnitude of the treatment effect. Precise
      methodological rules must be followed, but these rules are not known well enough
      in the scientific community. For example, particular care is necessary for the
      retrieval and selection of the trials: all available trials which satisfy
      predefined criteria of methodological validity should be taken into
      consideration. One of the main pitfalls in meta-analysis is the problem of
      unpublished trials, which represents a potential bias seen as an overestimation
      of treatment effect. In psychiatry, the applications of meta-analysis are
      numerous, especially in the domain of the treatment of depressive disorders,
      which will be developed in this paper. Several meta-analyses have been performed
      to assess the efficacy of antidepressants in major depression, especially with
      the "new antidepressants", which include the specific serotonine reuptake
      inhibitors (SSRIs). To date, these meta-analyses have shown that the main
      advantage of SSRIs was that they were better accepted, but without being more
      efficacious compared with classic antidepressants. The results of several of
      these meta-analyses are to be interpreted with the potential biases in mind,
      especially the publication bias and selection bias. Clinicians must be aware of
      the difficulties encountered in the choice of outcome criteria, and in deciding
      how to deal with patients that withdraw from treatment early (intention to treat
      analysis is the least biased solution for this problem.). Meta-analysis can
      therefore be helpful in establishing medical references in psychiatry, and to
      organize consensus conferences, but the limits of this method must be clearly
      recognized.

PMID- 9035996
TI  - [Cytolytic hepatitis during treatment with phenothiazines: apropos of a case].
AB  - In contrast to the well known chlorpromazine-induced cholestatic hepatitis, we
      report the case of a schizophrenic patient who presents a cytolytic hepatitis,
      without any prior hepatic disease. Mr G. was first hospitalized for depressive
      symptomatology. A pseudo-nevrotic schizophrenia was diagnosed. Pretherapeutic
      clinical and biological data were normal. A treatment with chlorpromazine 400
      mg/day was given. At day 8, the patient was still anxious and began to be
      agitated. An increase to 500 mg/day of chlorpromazine posology and an addition of
      haloperidol 200 mg/day was implemented. At day 10, the following clinical
      symptoms appeared: 38.6 degrees C fever; headache; myalgia; epigastralgia and
      hypocondrium pain. Biological hepatitis disturbances (ALAT, 984 U/L; ASAT, 414
      U/L) and hypereosinophilia with normal white cell count were found. Clinical and
      biological investigations were normal. Blood-culture, A, B, C hepatitis, HIV and
      CMV serologies were negative. Neuroleptic treatment was discontinued. Evolution
      to normality of the disturbances and biological data suggested a cytolytic
      hepatitis. Mr G... remained treated with flupentixol without side-effects.
      Phenothiazine-induced cholestatis is frequent, mild, and recovers spontaneously.
      The biological mechanism is supposed to be immunologic. Prevalence of biological
      hepatic disturbances is 10 to 20% with chlorpromazine in long-term treatment.
      More often, symptomatology is the same; jaundice, pruritus, abdominal pain,
      fever. Although pharmacological data suggest for a cytotoxic activity of
      phenothiazines, cytolytic hepatitis is poorly described. Maximum range of
      transaminase blood level reported in previous studies is about 400 U/l. This
      level is not clearly correlated with hepatic cell lysis. Few cases of hepatic
      necrosis have been reported. In all cases, preexistent hepatic injuries were
      observed. Chlorpromazine-induced cytolytic hepatitis is uncommon and cholestatic
      hepatitis mild. Biological hepatic parameters investigations remain necessary
      during neuroleptic treatment.

PMID- 9035997
TI  - [A case of Capgras syndrome with illusion of intermetamorphosis].

PMID- 9035998
TI  - [Substance abuse of midazolam (Hypnovel)].

PMID- 9035999
TI  - [Scales for assessing anhedonia. Response to questions by Dr. Pierson].

PMID- 9036000
TI  - [Schizophrenia: current research and perspectives. Proceedings of a conference.
      Lyon, France, 21-22 March 1996].

PMID- 9036001
TI  - [Intentional awareness and schizophrenia].

PMID- 9036002
TI  - [Organization and representation of action in schizophrenia].

PMID- 9036003
TI  - [Questions instead of conclusions].

PMID- 9036004
TI  - [Electrophysiologic studies].

PMID- 9036005
TI  - [Brain imaging in schizophrenic psychoses].

PMID- 9036006
TI  - [Cortical atrophy of the left temporal lobe and schizophrenic disorders. Apropos
      of 7 cases].

PMID- 9036007
TI  - [Risk factors and schizophrenia].

PMID- 9036008
TI  - [Schizophrenia and the corpus callosum: morphologic and functional approach].

PMID- 9036009
TI  - [Schizophrenia and exclusion. Current and future perspectives].

PMID- 9036010
TI  - [Stressful life change events and criminal behavior in schizophrenia].

PMID- 9036011
TI  - [Exclusion and very long term hospitalization: social and institutional
      environment].

PMID- 9036012
TI  - [Schizophrenia and exclusion. Reflections on a short-term hospitalization at the
      Polyclinic 18 de Malakoff].

PMID- 9036013
TI  - [Neurodevelopmental models of schizophrenia].

PMID- 9036015
TI  - [Schizophrenia and neural transmission: an excess of analogical treatment?].

PMID- 9036016
TI  - [Agonistic terror and schizophrenia].

PMID- 9036014
TI  - [Season of birth, obstetric complications and schizophrenia].

PMID- 9036017
TI  - 5th United European Gastroenterology Week. Paris, 2-6 November 1996. Abstracts.

PMID- 9036018
TI  - Air toxics: biomarkers in environmental applications. Houston, Texas, April 27
      28, 1995. Proceedings.

PMID- 9036019
TI  - Conference on beryllium-related diseases. Research Triangle Park, North Carolina,
      November 8-10, 1994. Proceedings.

PMID- 9036020
TI  - The 2nd NIEHS Predictive-Toxicology Evaluation Experiment: 30 chemical
      carcinogenicity bioassays.

PMID- 9036021
TI  - [Changes in myocardial Tc-99m-sestamibi uptake in asynergic territories during
      low-dose echo-dobutamine test].
AB  - BACKGROUND: Recent data suggest that contractile reserve in dysfunctional but
      viable myocardium during low-dose dobutamine infusion might be elicited not only
      by a direct inotropic stimulation but also by an increase in coronary blood flow.
      Aim of the study was to evaluate the effects of low-dose dobutamine on myocardial
      perfusion and function in asynergic but viable myocardium. METHODS: Nineteen
      patients with coronary artery disease and severe regional dysfunction were
      studied. Both regional ventricular function and myocardial perfusion were
      assessed at rest (PRE), during low-dose dobutamine (DOB) and, in twelve patients,
      after revascularization (POST). Regional ventricular function was evaluated with
      two-dimensional echocardiography using a score index ranging from 1 to 4.
      Myocardial perfusion was studied using Tc-99m-sestamibi Single Photon Emission
      Tomography (SPET); uptake defects were graded from 0 (normal) to 4 (absent
      uptake). For both evaluations the left ventricle was divided in 16 segments and
      two vascular territories were considered. RESULTS: Low-dose dobutamine elicited
      contractile reserve in 12 of 24 asynergic vascular territories (DOB+). Compared
      with PRE scintigraphy, DOB SPET showed perfusion improvement in 10/12 DOB+ and in
      3/12 DOB- asynergic territories (p = 0.006). Mean uptake score decrease
      significantly in DOB+ (from PRE SPET 21.0 +/- 7.2 to DOB SPET 17.6 +/- 7.1; p =
      0.0005) but not in DOB- (from SPET PRE 19.0 +/- 5.3 to SPET DOB 19.5 +/- 6.8, p =
      NS) abnormal territories. Fourteen asynergic territories underwent
      revascularization. Among them, 9 showed functional recovery after intervention
      (viable myocardium) and 5 showed no changes (fibrotic myocardium). A functional
      improvement under dobutamine was observed in 7 viable and in 1 fibrotic
      territories. Conversely, perfusion improved under dobutamine in 8 viable and in
      one fibrotic territory. After revascularization the perfusion defect score
      decreased significantly in viable territories (from PRE SPET 22.1 +/- 7.9 to POST
      SPET 13.3 +/- 6.6; p = 0.00001) but not in fibrotic regions (from PRE SPET 17.8
      +/- 6.0 to POST SPET 15.6 +/- 4.9). CONCLUSIONS: In asynergic myocardium
      contractile reserve elicited by low-dose dobutamine is associated in most cases
      with an improvement in Tc-99m-sestamibi uptake. This suggests a possible link
      between increased blood flow and functional improvement during dobutamine in
      viable myocardium.

PMID- 9036022
TI  - [Evaluation of myocardial viability very early after acute myocardial infarction
      by ultra-low dose echo-dipyridamole test].
AB  - BACKGROUND: After an acute myocardial infarction (AMI), stunned myocardium may
      cause a reversible left ventricular dysfunction. Dipyridamole echocardiography
      (0.56 mg*kg-1 over 4' e 0.84 mg*kg-1 over 10') can identify viable myocardium but
      can also induce ischaemia. AIM OF THE STUDY: To evaluate the usefulness of "Infra
      low" dose dipyridamole echocardiography for identification of myocardial
      viability. METHOD AND RESULTS: Of thirty-four consecutive in-hospital patients,
      thirty (26 males; mean age 59 +/- 11 years) with AMI separately underwent (40 +/-
      12 hours from symptoms onset): 1. a baseline resting echo (BASELINE); 2. a low
      dose dobutamine (DOB) echotest (5-10 mcg*kg-1*m-1 for 5') (DOB5, DOB10); 3. an
      "infra-low" dose dipyridamole echotest (0.28 mg*kg-1 over 4') (DIP). A pre
      discharge resting echo was performed 7 days after admission (follow-up). No
      patient developed echocardiographic or electrocardiographic signs of ischaemia
      after DIP, while 4 patients developed ischaemia after DOB. The systolic blood
      pressure (112 +/- 18 mmHg) did not change after both DOB and DIP. The heart rate
      was unchanged after DIP (BASELINE = 73 +/- 18 bpm', DIP = 75 +/- 14 bpm'), while
      it increased after DOB (BASELINE 69 +/- 11 bpm'; DOB5 = 71 +/- 11 bpm', p = 0.02;
      DOB10 = 74 +/- 12 bpm', p = 0.001). Wall motion score index (WMSI), in a 16
      segment model (from 1 = normal to 4 = diskinetic) (BASELINE = 1.64 +/- 0.3),
      improved after DIP (1.56 +/- 0.36, p < 0.05 vs BASELINE) and after DOB10 (1.50 +/
      0.36, p < 0.05 vs BASELINE) while did not change after DOB5 (1.59 +/- 0.35, p =
      n.s.). WMSI decreased at follow-up (1.53 +/- 0.31, p < 0.05 vs BASELINE); DIP and
      DOB10, but not DOB5, correctly predicted the WMSI decrease observed at follow-up.
      Results of DOB5, DOB10 and DIP were fully concordant in 118 segments (67%) (kappa
      = 0.54): 13 (7%) with concordant positivity and 105 (60%) with concordant
      negativity; 58 (33%) segments showed different results. At follow-up 54 (30%) of
      the 178 segments with baseline dysfunction, observed in 29 survivors, showed an
      improvement of grade 1 or more (viable). Two patients did not undergo DOB10;
      therefore, of the 168 segments with baseline dysfunction, in 27 survivors who
      underwent all tests, 54 (32%) showed an improvement of grade 1 or more (viable) e
      114 (68%) showed no improvement (not viable). Of 25 DOB5 "responders" segments,
      11 (44%) showed spontaneous recovery at follow-up (true-positive); of 153 "non
      responders" segments, 110 (72%) showed no spontaneous recovery at follow-up (true
      negative). Of 61 DOB10 "responders" segments, 29 (47%) showed spontaneous
      recovery at follow-up (true positive); of 107 "non responders" segments, 82 (77%)
      showed no spontaneous recovery at follow-up (true-negative). Of 36 DIP
      "responders" segments, 19 (53%) showed spontaneous recovery at follow-up (true
      positive); of 142 "non responders" segments, 107 (75%) showed no spontaneous
      recovery at follow-up (true-negative). The sensitivity of DOB5, DIP and DOB10 for
      predicting short-term spontaneous recovery was 20, 35 and 53% (DOB10 vs DOB5: p <
      0.001), respectively; specificity was 88, 86 and 71% (DOB5 vs DOB10: p = 0.002;
      DIP vs DOB10: p = 0.01); the positive value was 44, 52 and 47% (p = n.s.) and the
      negative predictive value was 72, 75 and 76% (p = n.s.) while the diagnostic
      accuracy was 67, 70 and 85% (p = n.s.). CONCLUSIONS: "Infra-low" dose
      dipyridamole echocardiography appears to be a hemodynamically neutral stress
      which does not modify either heart rate or blood pressure. It allows to explore
      selectively the viability of stunned myocardium, without eliciting ischaemia; it
      shows a good overall concordance with low-dose dobutamine and a low sensitivity
      but an excellent specificity for predicting spontaneous recovery early after AMI.

PMID- 9036023
TI  - [Motivations and expectations of physicians ordering an echocardiogram and the
      contribution of transthoracic echocardiography to the clinical practice. The
      Ligurian Group of the Italian Society of Cardiovascular Echography].
AB  - BACKGROUND: Echocardiography is the cardiological diagnostic test the use of
      which has increased most in recent years. However, despite the popularity and the
      massive use of the technique, there is little information regarding the
      usefulness and management impact of echocardiography as routinely ordered in
      current medical practice. Furthermore, clinical indications and expectations of
      physicians who ordered an echocardiogram (echo) have never been systematically
      evaluated in our country. METHODS: During the last two weeks of September 1994, a
      prospective, observational study was carried out at echocardiographic
      laboratories in 9 hospitals. By means of a questionnaire completed by the
      physician who ordered the test prior to its performance, we surveyed:
      characteristics of the ordering physician, reasons for ordering the test,
      physicians' expectations regarding the test, and pre-echo clinical diagnosis as
      well as clinical evaluation of presence or absence and severity of specific
      cardiac abnormalities. In addition, pre-echo clinical and instrumental assessment
      of specific cardiac abnormalities was compared with echocardiographic findings.
      RESULTS: Three hundred and forty-eight questionnaires were successfully
      completed: 42% by cardiologists (C), 30% by general practitioners (GP), 18% by
      internists (I), and 10% by other specialists (Sp). Forty percent of the echoes
      were ordered to "Reevaluate a known cardiac disease" (62% C, 19% GP, 14% I and 5%
      Sp; p = 0.0001), 39% to "Confirm or exclude a clinical suspicion" (40% C, 24% GP,
      24% I, and 12% Sp; p = 0.03), and 21% because of "Screening" purposes (40% GP;
      32% C, 15% Sp, and 13% I; p = 0.0017). In the patients who had had a previous
      echo, the expectation of a significant change with respect to the previous one
      was "Low" for 48% (57% C, 28% GP, 12% I, and 3% Sp; p = NS), "Moderate" for 42%
      (44% C, 38% GP, 12% I, and 6% Sp; p = NS), and "High" for only 10% of physicians
      (58% C, 17% GP; 17% I, and 8% Sp; p = NS). Physicians reported that their
      expectations from the result of the test on patients' management were: "Modifying
      therapy or clinical management of the patients" for 66% (45% C, 24% GP, 20% I,
      and 11% Sp; p < 0.0001), "Objective documentations of presence/absence of cardiac
      disease" for 21% (40% GP, 35% C, 15% I, and 10% Sp; p = NS), and "Patient's
      reassurement" for 13% (62% GP, 30% C, 6% I, and 2% Sp; p < 0.0001). The
      expectation that the result of the echo would influence therapeutic and/or
      clinical management of the patient was "Moderate" for 44% (42% C, 29% GP, 20% I,
      and 9% Sp; p = NS), "Low" for 36% (43% C, 34% GP, 15% I, and 8% Sp; p = NS), and
      "High" for only 20% of the physicians (50% C, 23% GP, 17% I and 10% Sp; p = NS).
      The echo report was judged in agreement with pre-echo clinical assessment in 40%
      of cases, in disagreement in 32% and compatible in 28%. At the echo examination,
      clinical left ventricular (LV) enlargement was not confirmed in 45% of cases and
      was clinically unsuspected in 13%; clinical LV systolic dysfunction was not
      confirmed in 53% of cases and was clinically unsuspected in 6%; clinical LV
      hypertrophy was not confirmed in 43% of cases and was clinically unsuspected in
      14%; clinical moderate or severe mitral regurgitation was not confirmed in 32% of
      cases and was clinically unsuspected in 9%; clinical left atrial enlargement was
      not confirmed in 27% of cases and was clinically unsuspected in 12%. CONCLUSIONS:
      GPs ordered echoes mainly for screening or to evaluate suspected cardiac
      abnormalities for the purpose of reassuring their patients or documenting the
      presence or absence of a cardiac disease. C ordered echoes to evaluate clinically
      suspected cardiac abnormalities or to reassess known cardiac diseases with the
      purpose of modifying patients' therapy or clinical management. One echo out of 3
      gave clinically unsuspected results. In 1 echo out of 2 clinical assessment of
      the severity of the most common morpho-functional cardiac abnormalities was cha

PMID- 9036024
TI  - [Comparison of the echo-dobutamine-atropine test and ergometric test in the
      diagnosis of coronary disease].
AB  - BACKGROUND: A prospective study has been done on 46 patients with suspected
      coronary artery disease (CAD). They had no history of myocardial infarction (MI)
      and a normal basal kinetic echocardiography. This was done in order to evaluate
      the overall accuracy of dobutamine-atropine stress echocardiography (DAS) compare
      to exercise stress test (ET) for the diagnosis of CAD. METHODS: All the patients
      after suspension of coronary therapy, performed a casual sequence with both
      maximal or symptom limited exercise testing (treadmill-Bruce protocol) and DAS.
      The dobutamine has been given while monitoring systemic blood pressure,
      electrocardiography and echocardiography in steps of 10 mcg/kg/min' per 3 min' up
      to a maximum of 40 mcg/kg/min'. Atropine has been added (0.25-1 mg) in patients
      who did not reach the theoretical maximal cardiac frequency. The test is
      considered positive when kinetic segmental left ventricular dysfunction appeared.
      CAD was defined as 50% luminal area stenosis in at least 1 coronary artery at
      coronary angiography. RESULTS: Significant CAD was present in 27/46 patients
      (59%). Compared with ET, DAS had significantly higher sensitivity (59% vs 92%, p
      = 0.01). The different sensibility between the two tests was higher on these
      patients with a 1 vessel disease (40% vs 86%, p = 0.02). There were no
      significant differences in specificity among the two tests (79% vs 84%,
      respectively). Differences in overall accuracy between ET and DAS were
      significant (67% vs 89%, p = 0.02). CONCLUSIONS: The results of our study show
      that the DAS is a safe and feasible technique with high sensibility (especially
      in patients with single CAD) and specificity. This is a valid alternative to the
      traditional ET, especially for these patients unable to exercise or these who are
      poorly motivated to achieve a work load sufficient to make the test
      interpretable.

PMID- 9036026
TI  - [Bundle-branch reentry ventricular tachycardia induced by sinus beat].
AB  - A spontaneous episode of bundle branch reentry ventricular tachycardia was
      recorded in a 50 year old man few weeks after operation for a severe aortic valve
      regurgitation. After surgery, the patient developed recurrent syncope and showed
      a bradycardia-dependent left bundle branch block and a HV interval of 70 ms. A
      bundle branch reentry ventricular tachycardia with left bundle branch block
      morphology, easily induced during premature ventricular stimulation, occurred
      spontaneously after the longest sinus cycle of a sequence conducted to the
      ventricles with a left bundle branch block morphology of the QRS complexes.
      During left bundle branch block an incomplete and concealed anterograde
      conduction along the left bundle branch was supposed to be present and its
      disappearance was considered the trigger mechanism of the spontaneous ventricular
      tachycardia. The negative results obtained with the signal-averaged ECG in our
      case support the concept that intramyocardial delay is not essential for this
      type of ventricular tachycardia.

PMID- 9036025
TI  - [Use of esophageal atrial electrogram and an external Thera VDD pacemaker in
      atrial-triggered ventricular pacing in acute myocardial infarction complicated by
      total AV block and low cardiac output].
AB  - Aim of this short report is to present a simple and fast technique to pace in VDD
      mode patients with acute myocardial infarction associated with third degree AV
      block and haemodynamic deterioration. VDD pacing was obtained using atrial
      electrogram recorded by trans-oesophageal catheter and a Medtronic Thera VDD pace
      maker as temporary pace-maker.

PMID- 9036027
TI  - [Verrucous abacterial endocarditis and polymyositis. A possible association?].
AB  - We describe a case of a verrucous non-bacterial endocarditis on the native mitral
      valve in a patient with polymyositis. This case, to our knowledge, represents the
      first report in the literature we could get. The case reached our attention after
      an episode of acute limb ischemia which lead to an echocardiographic examination
      that showed vegetations on the valve. No cardiac signs or symptoms were evident.
      We discuss the possible relation between the two disorders. The possibility of
      autoimmune diseases, other than lupus or lupus-related disorders, to produce this
      kind of lesions should be confirmed by a systematic echocardiographic study of
      these patients even if they have no evidence of cardiac involvement.

PMID- 9036028
TI  - [Anticoagulant or antiaggregant therapy in the secondary prevention of myocardial
      infarct?].
AB  - The recent publication of the results of two large trials of secondary prevention
      of myocardial infarction with oral anticoagulants is causing a revival of
      interest for oral anticoagulants in this clinical setting. On the basis of these
      data, oral anticoagulants should be considered not only an effective preventive
      strategy, but, probably, more effective than antiplatelet agents, currently the
      standard therapy in the prevention of thrombosis in acute myocardial infarction.
      There are advantages and disadvantages for both these treatments, and an adequate
      balancing of expected risks and benefits has to be performed in each single
      patient. The present review summarizes rationales and main clinical results in
      the prevention of reinfarction with antiplatelet agents and with oral
      anticoagulants, and analyzes the reasoning to prefer the formers or the latters
      in daily clinical practice of secondary prevention of coronary artery disease.
      Also, an analysis of the benefit/risk ratio of antiplatelet agents (aspirin) and
      oral anticoagulants in the Italian health system is synthetically presented. Such
      an analysis can be useful for the formulation of general guidelines and may
      suggest a modification of currently established and widely popular therapeutic
      habits in the management of coronary artery disease in Italy.

PMID- 9036029
TI  - [Dispersed cardiology and department therapy].

PMID- 9036030
TI  - [The papyri and the technological evolution: to be physician today].

PMID- 9036031
TI  - [Story of a changing relationship].

PMID- 9036032
TI  - [The trap of nostalgia].

PMID- 9036033
TI  - [Considerations on the article by A. Masoni (Physicians and medicine: what has
      changed) and the reply by C. Vecchio (To be physician today)].

PMID- 9036034
TI  - [Reflections on "diverse medicine"].

PMID- 9036036
TI  - [Physicians in the years '40, physicians in the years '90].

PMID- 9036035
TI  - [Science and conscience in medical practice today].

PMID- 9036037
TI  - [What information is given by controlled clinical trials (pharmacological and
      nonpharmacological) for anti-arrhythmia therapy in the prevention of sudden
      death?].

PMID- 9036038
TI  - [Clinical experience with the use of implantable vascular systems in advanced
      heart failure].
AB  - BACKGROUND: Patients with end-stage cardiomyopathy frequently require acute or
      chronic infusional treatments and long hospitalization. Availability of a simple
      and safe vascular access is a true necessity for these patients, especially in
      case of inotropic or diuretic outpatient treatment. In this study we have
      evaluated the usefulness and the applicability of implantable vascular access in
      the management of end-stage cardiomyopathy. Technical problems and both short and
      long term complications have been analysed. METHODS: Nineteen implantable
      vascular system (16 Port-A-Cath, Pharmacia; 3 Celsite, Bruneau) have been
      implanted in a group of 15 patients with end-stage cardiomyopathy. All patients
      had been previously hospitalized and needed prolonged infusional therapy.
      Implantation was performed in local anaesthesia with technique derived from pace
      maker implantation. RESULTS: All the interventions were well tolerated, average
      procedural time was 30 min (range 20-60 min). No procedural complications
      occurred. Re-implantation of the system was required in 2 patients due to
      catheter thrombosis, In 1 patient due to catheter rupture caused by wrong
      positioning of infusion needle, and in 1 patient due to inflammatory reaction. In
      2 further cases catheter thrombosis was treated with local infusion of urokinase.
      In 1 patient the catheter was repositioned after dislocation. The average in situ
      permanence of the systems was 8 months (range 15 day-18 months). CONCLUSIONS:
      Vascular implantable systems have proved useful and easily applf1p4e in the
      management of patients with end stage cardiomyopathy. After training some of the
      implied complications are easily avoidable. The use of this device has concurred
      to reduce duration and frequency of hospitalizations.

PMID- 9036039
TI  - [Cardiac troponin I and T in unstable angina: incidence, correlation, kinetics of
      release and prognostic value].
AB  - BACKGROUND: The aim of this study was to ascertain the incidence of altered serum
      cardiac Troponin-T (cTnT) and cardiac Troponin I (cTnI) in patients with unstable
      angina, the concordance between findings for the two proteins, their release
      kinetics and their utility in predicting coronary events. METHODS: We studied 32
      consecutive patients (pts) admitted to the Coronary Unit with a diagnosis of
      unstable angina; following Braunwald classification criteria, 5 pts were in class
      I, 4 class II, 23 class III. A blood sample was taken on admission to hospital
      and subsequently every 8 hours for two days, a total of 7 samples being obtained
      per pt. Cardiac-TnT values ranging from 0-0.17 mugr/L (Boehringer Mannheim) were
      considered normal, as were cTnI values ranging from 0 to 0.7 mugr/L (Stratus
      Dade). RESULTS: Among 218 samples, altered cTnT values (0.18-0.68 mugr/L) were
      found in 19 (3 pts), and 13 of these samples were positive for cTnI (0.8-5.5
      mugr/L), while the remaining 6 showed borderline values for cTnI (0.5-0.7
      mugr/L). No cTnT negative samples were found to be positive for cTnI. The release
      kinetics of cTnT and cTnI were comparable in all three cases, with a "plateau"
      pattern, unlike the kinetics in the course of acute myocardial infarction (AMI).
      The mean follow-up was 13 months on average (range 1-19). In two pts with altered
      cTnT and cTnI values, symptoms were controlled with medical therapy, while the
      remaining patient failed to respond to medical therapy and therefore underwent
      PTCA. Fifteen months later, they are alive and have not had myocardial
      infarction. Of the 29 pts with normal cTnT and cTnI values, three developed AMI,
      which in two cases was fatal. Seven pts were submitted PTCA, seven to aorto
      coronary bypass surgery, two were subsequently rehospitalized for a recurrent
      angina symptoms. In 13 pts complete control of symptoms was achieved with medical
      therapy. CONCLUSIONS: Our findings demonstrate that the incidence of altered cTnT
      and cTnI values in pts with unstable angina is low; there is close agreement
      between findings for the two proteins; in cases of angina, the cTnT and cTnI
      release kinetics are different from those in AMI. The finding of altered cTnT and
      cTnI values in the serum of our pts with unstable angina does not appear to be of
      prognostic value for future coronary events.

PMID- 9036040
TI  - [Heart surgery with cardiopulmonary bypass in patients on chronic dialysis
      treatment: our experience].
AB  - METHODS: To determine the mortality and the morbidity of cardiac surgery in
      patients on chronic hemodialysis, we retrospectively reviewed eighteen adult
      patients (13 males and 5 females) with a mean age of 54.7 years (range: 30-67
      years) who underwent cardiopulmonary bypass procedures between 1987 and 1995. The
      operations included: isolated coronary artery bypass grafting in 12 patients,
      coronary artery bypass grafting plus mitral ring annuloplasty in 1 patient, mitro
      aortic valve replacement in 2 patients, isolated aortic valve replacement in 1
      patient, aortic valved conduit implantation in 1 patients and mitral valve
      replacement plus tricuspid annuloplasty in 1 patient. There were 10 and 3
      patients in CCS functional classification III and IV respectively; 1 and 4
      patients were in NYHA classification II and III respectively. All of them were
      hemodialyzed the day before surgery: the average time they had been on
      hemodialysis was 6.5 years. Anesthesia and the cardiopulmonary bypass (CPB) in
      these patients required attention in order to provide the optimal fluids and
      electrolytes balance: particularly intravenously administered fluids were kept to
      a minimum and drug dosages were reduced to recommended levels for anephric
      patients. An hemoconcentrator was used in all patients during the CPB and, in the
      last 4 cases, we used a dialysis filter and a sterilized perfusional solution to
      reduce the level of potassium and to put off postoperative dialysis. RESULTS: In
      three patients there were major bleeding problems resulting in reoperation; 5
      perioperative deaths occurred: two of them due to myocardial infarction and three
      due to irreversible low cardiac output state. In our experience there were four
      late deaths: one patient died four months after surgery for chronic heart
      failure, another one died twelve months after surgery for dilated cardiomyopathy
      and two patients died respectively seventeen and seventy two months after
      discharge for myocardial infarction. Two of the remaining patients reported
      recurrence of angina while the others achieved symptomatic improvement.
      CONCLUSIONS: In conclusion, cardiac surgery is performed on chronic renal
      dialysis patients with high mortality and morbidity and it's indicated only if
      medical treatment is ineffective. The successful surgical results, obtained with
      an adequate management between surgeons, anesthesiologists and nephrologists,
      don't assure the long-term survival of the patients.

PMID- 9036041
TI  - [Mitochondrial cardiomyopathies: a new entity in cardiology research and
      diagnosis].

PMID- 9036042
TI  - [Congenital cardiomyopathies and sudden death].

PMID- 9036044
TI  - [Physicians and medicine: what and how has changed].

PMID- 9036043
TI  - [Echocardiography versus cardiac catheterization for surgical indications in the
      era of DRG: cost-benefit analysis].

PMID- 9036045
TI  - [To be a physician today: answer to Masoni].

PMID- 9036046
TI  - [The nitrates in cardiac decompensation].

PMID- 9036047
TI  - [Endothelial function, nitrate derivatives and cardiac insufficiency].

PMID- 9036048
TI  - [Physiopathologic and pharmacodynamic rationale for the use of nitrate compounds
      in cardiac decompensation].

PMID- 9036049
TI  - [Clinical and diagnostic indications for the use of nitrates in dynamic heart
      defects (decompensation, left ventricular dysfunction without decompensation,
      etc].

PMID- 9036050
TI  - [Pharmacologic interactions with nitrates in patients with, or at risk of,
      cardiac decompensation].

PMID- 9036051
TI  - [Nitrate compounds in patients awaiting heart transplantation].

PMID- 9036052
TI  - [The role of nitrates in left ventricular insufficiency in patients with acute
      myocardial infarction].

PMID- 9036053
TI  - [Effectiveness, tolerance, adverse effects of prolonged therapy with nitrate
      compounds].

PMID- 9036054
TI  - [Dobutamine echocardiography and positron emission tomography in the assessment
      of viable myocardium after a thrombolized acute myocardial infarction. Comparison
      with spontaneous recovery].
AB  - BACKGROUND: Aim of the present study was to compare the ability of low-dose (5-10
      gamma/Kg/min) dobutamine echocardiography (DE) and of positron emission
      tomography (PET), performed after a thrombolized acute myocardial infarction
      (AMI), to predict the spontaneous functional recovery (SFR) of viable but
      akinetic myocardial segments. PATIENTS AND METHODS: Twenty-one pts were studied
      by DE, 10 +/- 2 days (DE1) and 31 +/- 2 days (DE2), after a thrombolized AMI, and
      by PET (18F-FDS, glucose load) within 7 days after DE2; a basal echo was also
      performed 3 months after AMI. The left ventricle was divided in 16 segments, both
      in echo and PET examination. DE viability was defined as improvement in wall
      motion of akinetic seg; PET viability was defined as an FDG uptake > or = 40% of
      the maximum. RESULTS: In the 89 akinetic segments, DE1, DE2 and PET,
      respectively, identified, 16, 27 and 60 viable segments; the concordance with
      PET, in viable and not viable segments, resulted of 50% for DE1 and of 62% for
      DE2. After 3 months 29/89 segments had a SFR. In comparison with SFR the
      sensitivity of DE1 and DE2 was lower (51% and 68%) than PET (89%); the
      specificity was higher for DE1 and DE2 (98% and 96%) respect to PET (43%).
      CONCLUSIONS: In comparison with DE performed 10 days after a thrombolized AMI, DE
      performed 30 days after AMI revealed a greater extension of viable myocardium and
      a greater diagnostic accuracy in predicting SFR of akinetic segments. The
      concordance between DE and PET is high, if all myocardial segments are
      considered, and lower, if only akinetic segments are considered; in fact, PET
      identifies, as viable, a greater number of segments. In comparison with SRF, DE
      revealed the greatest specificity and PET the greatest sensitivity.

PMID- 9036055
TI  - [Acute cytolytic hepatitis in azathioprine hypersensitivity].

PMID- 9036056
TI  - [Collagenous colitis, does it belong in the family of chronic intestinal
      inflammatory diseases?].

PMID- 9036057
TI  - [Photodynamic laser therapy of advanced breast carcinomas].

PMID- 9036058
TI  - [Patient related and medical progress--the planned bioethics convention of the
      European Council].

PMID- 9036059
TI  - [Correlation between anxiety and pain in the first gynecological examination of
      children and adolescents].

PMID- 9036060
TI  - [Information by the German Cancer Society].

PMID- 9036061
TI  - [HPV-Dna hybridization allows differentiation of cervix lesions in PAP III
      cytologic findings].
AB  - A repeat Pap smear as well as a smear for human papillomavirus (HPV)-DNA
      detection with the Hybrid Capture assay (Digene diagnostics/Murex, Burgwedel)
      were collected from 30 women with Pap smears recurrently classified as "Pap III".
      All patients underwent colposcopy and histological assessment. The repeat Pap
      smear distinguished correctly in 15, colposcopy in 19 and the Hybrid Capture
      assay in 27 cases between neoplastic and inflammatory lesions. All invasive
      neoplasms were positive for HPV-DNA. HPV typing seems to be a suitable non
      invasive method for early selection of cervical lesions that need histological
      assessment in women with smears classified as "Pap III".

PMID- 9036062
TI  - [Electrosurgical loop excision of the transformation zone in treatment of cervix
      neoplasia].
AB  - 100 patients with CIN on referral Pap and with a distinct cervical lesion on
      colposcopy were treated with the loop electrosurgical excisional procedure
      (LEEP). Compared with 60 women who underwent cold-knife conization, the number of
      lesions classified as CIN-3 or more did not differ between the two groups (53% vs
      53.3%). Severe haemorrhage and cervical stenosis were only observed after
      conization. Involvement of resection margins was found in 18% of all LEEP and in
      16.7% of all cone biopsies. 3-12 months after LEEP the rate of cytologically and
      biopsy proven neoplasia was 2.2%. LEEP is a safe and effective procedure and
      should be used as the treatment of choice for distinct cervical lesions.

PMID- 9036063
TI  - [Results of adjuvant chemotherapy of operated high risk cervix carcinoma].
AB  - Patients with carcinoma of the cervix and histologically proven blood vessel
      invasion have a poor prognosis. At the I. Frauenklinik der Universitat Munchen,
      34 women were enrolled for a prospective study and were alternatively treated
      with or without adjuvant chemotherapy (carboplatin and 5-fluorouracil). Of the 28
      patients included in the follow-up (14 with/14 without chemotherapy), 12 patients
      died (5 with/7 without chemotherapy). The disease-free interval was 18.6 months
      in the group treated with chemotherapy compared to 29.3 months in the group
      without chemotherapy. There is no statistically significant difference in the
      survival of patients with blood vessel invasion in relationship to adjuvant
      chemotherapy following radical hysterectomy.

PMID- 9036064
TI  - [13-cis retinoic acid and interferon-alfa-2a as palliative therapy in pretreated,
      recurrent squamous epithelial carcinoma of the cervix uteri and vulva].
AB  - Patients with metastasising carcinoma of the uterine cervix or recurrent disease,
      in whom local treatment as surgery or radiotherapy has failed, are still an
      unsolved problem. Platinum-based multi-agent chemotherapies achieve overall
      response rates up to 60%, but side effects are serious and so far no survival
      benefit has been proven. Recent publications report on a synergistic effect of
      combination therapy using 13-cis-retinoic acid and interferon alpha-2 a in the
      treatment of squamous cell carcinoma of the cervix. In a pilot study we include 6
      patients with locally recurrent or metastasising squamous cell carcinomas, five
      of the uterine cervix, one of the vulva. The systemic therapy consisted of-orally
      administered 13-cis-retinoic acid (80 mg q. d.) and subcutaneously injected
      interferon alpha-2 a (6 x 10(6) I.E. q. d.). All patients were primarily treated
      by surgical and/or radiation therapy. In each case chemotherapy had been either
      already performed or rejected by the patient. Median duration of treatment was 52
      days, median survival time 107 days. Out of 6 patients 3 experienced progression
      of disease uninfluenced by therapy. One patient with multiple subcutaneous lymph
      node metastases showed mixed response for a short period of 3 weeks before
      progression and eventual death. One patient had no change or disease for 13
      months with subsequent progression and eventual death after 22 months. One
      patient could not be evaluated for an allergic reaction after only 15 days of
      treatment. Other side effects were "flu-like symptoms", skin irritations,
      conjunctivitis sicca and chileitis, all WHO 1-2. Overall toxicity must be rated
      low compared to standard chemotherapy, but is not negligible. In our study the
      positive reports in literature concerning the treatment of primary advanced
      cervical cancer and recurrent advanced carcinoma of the skin could not be
      reproduced. This might be due to the small number of cases, which is a common
      problem in immunotherapeutic studies. Moreover, very unfavourable patient
      selection criteria in our study compared to primarily untreated patients may also
      have contributed to different response rates. However, in our opinion the tested
      regimen cannot be considered sufficiently effective in patients suffering from
      pretreated, recurrent squamous cell carcinoma of the cervix or vulva.

PMID- 9036065
TI  - [Sequential course and prospective management of ifosfamide-induced multi-organ
      toxicity].
AB  - We report on an 66-year old female in whom we diagnosed uterine carcinosarcoma
      and concurrent breast cancer. As first-line treatment the patient received
      ifosfamide 4.8 mg/m2 body surface. During her second course of chemotherapy she
      developed sequentially life-threatening toxicities; severe emesis followed by
      nephrotoxicity, neurotoxicity and myelosuppression. Early prophylactic
      administration of rhG-CSF (Filgrastim) helped to overcome severe, potentially
      fatal myelosuppression. The course of severe toxicities following high doses of
      ifosfamide might reflect a dependent sequence, where one organ failure causes a
      subsequent organ failure. Prophylactic treatment of anticipated toxicity should
      be considered for the management of severe ifosfamide-induced toxicity. Such
      treatment may consist of sufficient antiemesis, sufficient hydration, as well as
      a therapy with methylene blue in case of severe neurotoxicity.

PMID- 9036066
TI  - [Quality assurance in cytology by continuous registration of stage movement
      during microscopy work].
AB  - The discussion concerning the maximum workload of microscopical slides to be
      screened by doctors or cytotechnologists per unit of time has been activated in
      Germany by a "Guideline of the German Medical Association concerning quality
      assurance of cervical cytology". In this guideline the maximum workload is 8-10
      cases per hour. To control the adherence to these guidelines we have monitored
      the screening process by using Axio-HOME-Microscopes to register the microscope
      stage coordinates every twenty milliseconds. In a series of 8653 slides screened
      by 5 cytotechnologists the average screening time was 3 1/2 minutes followed by
      an average intercase interval of 2 minutes. The distribution of the screening
      work over the day was presented in form of daily working profiles, allowing a
      control of workload limits. The results did not indicate, that the screening time
      per case vary with the time of the day and the day of the week. Since this
      approach to quality assurance seemed practical also for routine cytology, all
      working places of the cytotechnologists at the Cytological Institute of the
      Bavarian Cancer Society have been equipped with this set up for quality
      assurance.

PMID- 9036067
TI  - [Prostaglandin-induced labor--is the prostaglandin E2 vaginal gel a "new"
      alternative?].
AB  - In Germany, intracervical application of 0.5 mg PGE2 gel and the 3 mg PGE2
      vaginal tablet are registered for induction of labour. Both methods are highly
      effective; however, the are associated with several problems in practice. Major
      problems of the intracervical route are the strict application of the gel into
      the cervical canal, not spreading it to the vaginal and/or extra-amniotic space,
      the "technical" difficulties of application in cases of an unfavourable cervix in
      a posterior position and the risk of artificial rupture of the membranes. The
      problems with the PGE2 vaginal tablet are the incalculable release and
      absorption, the unpredictable clinical response and the unclear definition of CTG
      monitoring intervals. The application of the 2 mg PGE2 vaginal gel has proved an
      efficient and practicable method for induction of labour in both the unfavourable
      and the favourable cervix. The advantages over the intracervical procedure are in
      particular the practicability and safety of administration, even in
      "anatomically" difficult situations (e.g., narrow cervical canal); the advantages
      over the PGE2 vaginal tablet are greater bioavailability with a quicker release
      and absorption, the more predictable clinical response and the closer correlation
      with the subsequent changes in cervical scores. Since well-defined comparative
      studies are lacking, no definite conclusions can so far be drawn regarding the
      method of choice for induction of labour. Recently, a prospective, randomised
      multi-centre study has gone under way to clarify this question.

PMID- 9036068
TI  - [Early diagnosis of congenital and acquired intrauterine causes of abortion by
      post-abortion hysteroscopy].
AB  - A prospective study was conducted on the incidence of intrauterine pathology
      after abortions diagnosed by post-abortion hysteroscopy. In 80 patients
      outpatient hysteroscopy was performed 8-12 weeks after a dilatation and curettage
      for incomplete or missed abortions. Intrauterine pathological changes were found
      in 40 patients. There were 10 cases of uterus subseptus/ bicornis and 7 of uterus
      arcuatus, 2 submucous myoma and 1 corpus polyp. Intrauterine adhesions were
      diagnosed in 20 patients. 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
      the first abortion (27.8% versus 14.9%). Post-abortion hysteroscopy is a simple
      and useful method for early diagnosis of congenital and acquired intrauterine
      pathology after abortions.

PMID- 9036069
TI  - [Hospital infections in gynecology and obstetrics. An inclusive prevalence study
      in Germany].
AB  - In a German multicenter survey, 2206 gynaecological patients in 72 randomly
      selected hospitals were examined for the prevalence of nosocomial infections and
      possible risk factors. Hospital-acquired infections were diagnosed in 1.45% of
      the patients. The most common localisation was the urinary tract (0.91%).
      Septicaemia, vaginitis and infections of the upper and lower airways were only
      rarely seen. The following endogenous risk factors were identified: diseases of
      the cardiovascular system (16.1%), malignancies (12.2%) preexisting infections
      (6.1%), obesity (5.9%), and diabetes (5.0%). The most common exogenous risk
      factors were peripheral venous catheters (19.9%), catheterisation of the urinary
      tract (7.2%) and wound drainage (28.6%). 49% of the patients who underwent
      caesarean section and 50% of the hysterectomy patients received antimicrobial
      chemoprophylaxis.

PMID- 9036070
TI  - [Analysis of a 1992 birth sample in Germany. 1: New percentile values of the body
      weight of newborn infants].
AB  - 14 of the 16 German Federal "Lands" ("Bundeslander") participated in the first
      assessment in perinatal medicine in reunited Germany. A total of stored data
      representing 563,480 single births were used to calculate percentile values for
      birth weight, size (length) at birth and circumference of the head from the 23rd
      week of pregnancy, presented in tabulated and graphic form. Only data of German
      Population were evaluated; no other selective criteria were applied. The
      percentile values were calculated via the cumulative frequencies. Besides the
      conventional somatic data, the length-related birth weight percentile values were
      also stated, since these enable a classification more in accordance with the
      fetal development of the newborn. A cursory comparison with other German standard
      value determinations and with Lubchenco's curve is carried out.

PMID- 9036071
TI  - [Proliferating serous papillary cystadenoma of the borderline type in myometrium
      of the fundus uteri].
AB  - The 68-year old patient with clinical signs of peritonitis was laparotomized, and
      a cystic, ruptured structure thought to be an endometriotic cyst was found
      intraoperatively in the fundus uteri. Histomorphological investigation, however,
      revealed a proliferating serous papillary cyst-adenoma (borderline tumour) of the
      myometrium with surrounding, partially atypical endosalpingiosis.

PMID- 9036072
TI  - [Tetralogy of Fallot with absent pulmonary valve--prenatal diagnosis and
      management in the 2nd trimester].
AB  - Tetralogy of Fallot with absent pulmonary valve is a rare congenital cardiac
      malformation detected in 3% to 6% of tetralogy of Fallot patients. The prognosis
      depends on respiratory complications. In the present case the diagnosis was made
      at 18 week's gestation with two-dimensional and Doppler echocardiography. A
      ventricular septal defect and overriding aorta, absent valve echo, pulmonary
      regurgitation, and cystic pulsatile dilatation of the left pulmonary artery were
      the main diagnostic criteria. Severe respiratory complications were assumed in
      combination with a hyperechogenic left lung and termination of pregnancy was
      performed at 20 weeks' of gestation.

PMID- 9036073
TI  - [Neurinoma in the area of an episiotomy scar. A case report].
AB  - Neuromas are caused by lesions of intact nerves. They are defective regenerates
      and are characterised by benign neoplastic proliferation. Little is known about
      the presence of neuromas in episiotomy scars or at the vulva. The authors
      describe the course of a neuroma in an episiotomy scar on the basis of a case
      report by the Department of Gynaecology of the University of Gottingen. Only few
      case reports have been published. Preoperative diagnosis is based on suspicion;
      imaging methods fail to yield relevant information in the majority of cases. The
      number of undiscovered cases of neuromas after trauma of the perineum/of the
      vulva, the size of which is often just 1 or a couple of millimetres, may be
      higher than assumed; quite often a possible organic cause is excluded from the
      very beginning by assuming the cause was psychosomatic. If diagnosis proves
      difficult, simple resection of the tissue containing the focal point of the pain
      is the therapy of choice after detailed patient history exploration and
      gynaecological examination.

PMID- 9036074
TI  - [Comprehensive assessment of household drinking water use in cities with
      unfavorable sanitary and epidemiological conditions].

PMID- 9036075
TI  - [Prognostication of anthropogenic chemical pollution of the Dnepr River].
AB  - Deterioration of the quality of surface waters has a negative impact on the
      quality of drinking water. Hence, mathematical prediction of anthropogenic
      contamination of water bodies, the main sources of drinking water, is a pressing
      task. Mathematical models have been created for predicting the content of the
      priority chemical compounds, namely, surfactants, heavy metals, oil products, in
      the Dnieper river and its basin.

PMID- 9036076
TI  - [Occupational and production-dependent morbidity among railway workers].
AB  - Presents data on the occupational diseases of railway workers in 1958-1994 and
      analyzes the nosological structure of morbidity with regard for the technological
      progress in various fields of this industry. Discusses the problems related to
      occupational diseases in this population. A disease is recognized as an
      occupational only in cases when occupational hazards cannot be eliminated by
      modern technology, but still, the victims are to have a life compensation from
      the work-giver for not providing the proper working conditions.

PMID- 9036077
TI  - [An experimental study of combined effects of toluene and general vibration].

PMID- 9036078
TI  - [Relationship of vitamins and microelements and their role in the prevention of
      iron deficiencies (review)].

PMID- 9036079
TI  - [Role of individual variability of the body in the formation of students'
      health].

PMID- 9036080
TI  - [The problem of universal hygienic standardization of chemical pollution of the
      environment based on the permissible daily dose].
AB  - Discusses the present state of the problem of universal hygienic standardization.
      Offers a model for prediction and assessment of comparative hazards of harmful
      substances upon inhalation and enteral exposure and for calculation of the
      permissible daily dose. Singles out the main prospective tasks for universal
      standardization of harmful substances.

PMID- 9036081
TI  - [Significance of personal hygiene habits in the prevention of enterobiasis].
AB  - The pupils from Rostov-on-Don were interviewed by a questionnaire on medical
      helminthology. They were found to poor knowledge in this sphere. They do not
      observe elementary personal hygienic rules. The ways of improving the hygienic
      education of pupils.

PMID- 9036082
TI  - [Comparative study of adaptation of school children from regions with radiation
      pollution and from Moscow to conditions of rest at Artek, a health center].

PMID- 9036083
TI  - [Effects of parents' exposure to genotoxic agents on the degree of maturity of
      the newborn].
AB  - The maturity of full-term newborns was studied by immunological, biochemical, and
      ecogenetic methods. The study yielded basic immunochemical and ecogenetic
      evidence. It shows that chronic intrauterine hypoxia and unfavourable ecogenetic
      factors apparently influence concurrently and result in severe fetal immaturity.

PMID- 9036084
TI  - [Comparative characterization of heat electric power plants as the source of
      atmospheric pollution by benz(a)pyrenes].

PMID- 9036085
TI  - [Effects of trivalent chromium on several processes of bioenergetics and adenyl
      nucleotide metabolism].

PMID- 9036086
TI  - [Formation of the Pirogov Society (the 110th anniversary of the Society of
      Russian Physicians in commemoration of N.I. Pirogov)].

PMID- 9036088
TI  - [Methods of the analysis of nitrosamines in food products].

PMID- 9036087
TI  - [Methodological approaches to the creation of a system of social-hygienic
      monitoring: aims, tasks and scenarios of the utilization of the system].

PMID- 9036089
TI  - [Principles of validating maximum allowable concentrations of atmospheric
      pollution in large tonnage release of waste].

PMID- 9036090
TI  - [Staphylococcal contamination of the upper respiratory tract mucosa in children
      exposed to air pollution].
AB  - The carriership of staphylococci, specifically, of the resident type, is highly
      prevalent among children living near gas industry plants. The authors
      characterize the relationships of the level of resident staphylococcal
      carriership in children with the intensity of chemical pollution of the
      atmosphere and with the incidence of respiratory diseases. They estimate the
      gradations of coefficients of resident carriership of staphylococci corresponding
      to certain levels of air pollution, which served the basis for spatial
      microbiological monitoring of atmospheric contamination in regions with gas
      industry plants.

PMID- 9036091
TI  - [Optimizing water use and protection of population health at territories of water
      streams with reverse and variable flows].

PMID- 9036092
TI  - [Drug therapy of benign prostatic hyperplasia].
AB  - BPH patients with Vahlensieck stage II or III disease are suitable for drug
      treatment. The points of attack are reduction of testosterone, conversion of
      testosterone to dihydrotestosterone, conversion of testosterone to estrogen using
      GnRH analogues, antiandrogens and alpha reductase inhibitors or aromatose
      inhibitors. Furthermore a reduction in obstruction is achieved through the use of
      phytopharmaceuticals containing 5-lipoxygenase and cyclooxygenase inhibitors. At
      present, Curcurbitae pepo seeds, Urtica dioica root, Pollinis siccae extract and
      Sabal serrulata seed extract are approved for the treatment of prostatic diseases
      in Germany. The use of alpha-1-sympathicolytic treatment may reduce muscular tone
      in the prostate. Combination of the various modes of action may also offer an
      effective form of treatment.

PMID- 9036093
TI  - [Benign prostatic hyperplasia: diagnosis in general practice].
AB  - Despite the availability of modern urological methods, the diagnosis and therapy
      of benign prostatic hypertrophy (BPH) continues to present problems that are due
      in part to the discrepancy between the patient's subjective symptoms and the
      objective findings. With the aim of achieving a "clear" picture of the actual
      indication or treatment, a differentiated approach involving a careful waighing
      up of the patient's history, symptoms, basic laboratory investigations and the
      use of conventional sonography would be desirable in the doctor's office. The
      present paper describes a rational concept for the "interface" between the
      general practitioner's office and that of the specialist.

PMID- 9036094
TI  - [Recognizing and treating depression. 1: Clinical picture and diagnostic
      procedure].

PMID- 9036095
TI  - [Mechanisms of action of intravenous immunoglobulins].
AB  - Intravenous immunoglobulins (IVIG) are now used to treat various diseases,
      including autoimmune diseases, systemic inflammatory diseases, allografts and for
      replacement therapy in the case of IgG deficiency. Only in some of the
      indications has the efficacy of this treatment been confirmed in large-scale
      studies. Also, in many cases the modes of action remain unclear. Principally, the
      following therapeutic strategies can be differentiated: Replacement treatment,
      blocking of the effector molecules, influencing of the cellular and humoral limbs
      of the immune defence system and interaction with cytokines. In certain CNS
      diseases, displacement of pathological immunoglobulins may be involved. It would
      be desirable to acquire more detailed knowledge about modes of action with the
      aim of using IVIG with greater specificity in the future.

PMID- 9036096
TI  - [What are the current indications for phytogenic psychotropic drugs?. Interview
      by Elisabeth B. Moosmann].

PMID- 9036097
TI  - [Philosophical principles of psychopathology].
AB  - The relation between psychopathology and scientific philosophy will be specified.
      The fundamental precondition of psychopathological thinking and its issue is the
      feature of conscious experiencing. This is a structure of elements reciprocally
      requiring each other. Based on this approach it will be shown that an atomizing
      labelling of mental disorders must be rejected. The integral correlation of
      conscious living must be the criterion providing a verifiable structure of
      symptoms of mental disorders. A distinct conception of this structure and its
      elements is for example lacking in K. Jaspers' and K. Schneiders' approach.
      Orientation towards the structure of conscious living requires new investigations
      of old and discussions of new psychopathological topics.

PMID- 9036098
TI  - [Sexual dimorphism of the human brain--a review of the literature].
AB  - Some findings of neurobiological brain research regarding structural sex
      differences of the human brain are reviewed and discussed. Besides the well known
      difference in brain size, especially some cell groups of the hypothalamus display
      differences between the sexes. The results obtained for other regions, such as
      the corpus callosum and other commissural systems, are inconclusive. Further
      dimorphisms involve the temporal lobes and sex-specific brain asymmetry. These
      differences seem to be subtle and are superimposed by high interindividual
      variability. Finally, little morphological support is found for behavioural
      differences between the sexes.

PMID- 9036099
TI  - [Combination therapies in antidepressive drug refractory depression--an
      overview].
AB  - Despite the availability of a wide range of effective antidepressant drugs,
      nearly 30% of depressed patients fail to respond to antidepressant treatment.
      Various pharmacological strategies have been developed to treat such refractory
      depression, of which augmentation therapies are one of the most important. This
      article reviews both benefits and risks of all known augmentation therapies.
      Among these treatment strategies the efficacy of lithium augmentation is very
      well documented by a large number of controlled studies - lithium augmentation
      can therefore be recommended in depression refractory to antidepressant
      treatment. The efficacy of triiodothyronine (T3) augmentation and the combination
      of different antidepressants - like a TCA-MAOI combination - is described in a
      large number of case reports and uncontrolled studies; the number of placebo
      controlled double blind studies, confirming the efficacy of these treatment
      strategies, is however relatively small. T3 augmentation and combined
      antidepressant treatment may therefore be considered in the treatment of
      refractory depression; in contrast to lithium augmentation these combination
      therapies are however only second-line strategies. Other augmentation therapies
      (TCA + stimulants, TCA + reserpine, TCA + yohimbine, TCA + fenfluramine, SSRI +
      buspirone) are very interesting clinical research strategies, but don't have too
      much importance in clinical practice at the moment.

PMID- 9036100
TI  - [The contribution of neuropsychology to psychiatry].
AB  - Human neuropsychology is the study of brain-behavior relationships based on the
      analysis of functional disturbances after brain damage. The assessment and
      analysis of pathological states and processes in the brain on cognition, speech
      and language, praxis, motivation and affectivity, represent the main topics of
      neuropsychological research. Patients with psychiatric disorders very often
      exhibit cognitive impairments which should also be assessed by means of specific
      neuropsychological diagnostic tools. The advantage of such tools is their
      validity and reliability which allow accurate qualitative and quantitative
      analysis and characterization of the various cognitive impairments.
      Neuropsychological methods of assessment can also be used for follow-up
      measurements, for example, in studies on the effect of medication. Finally, the
      outcome of a comprehensive neuropsychological assessment can provide a useful
      basis for the treatment of cognitive impairments in psychiatric patients using
      means that have proved successful in brain-damaged patients.

PMID- 9036101
TI  - [Chorea-like motor restlessness in clozapine].
AB  - Clozapine is an antipsychotic drug that has a very low incidence of
      extrapyramidal side effects. Only few dyskinetic and dystonic motoric alterations
      are described. This brief review describes three patients who developed chorea
      like symptoms during a Clozapine therapy. The possible causal mechanisms of these
      side effect are suggested.

PMID- 9036102
TI  - [Myositis--a rare complication of Crohn disease].
AB  - Crohn's disease is a chronic relapsing inflammatory disorder primarily affecting
      the gastrointestinal system. Extraintestinal manifestations such as erythema
      nodosum, iridocyclitis, arthritis and sclerosing cholangitis are frequent. We
      report on a 57-year old male patient with the symptoms of Crohn's disease.
      Clinically he showed signs of a muscle disorder and muscle biopsy demonstrated a
      perimysial inflammation with lymphocytes and histiocytes. Complete remission was
      achieved by immunosuppressive treatment. Six cases presented in the literature
      are reviewed and the autoimmunological aspects of the pathogenesis discussed.

PMID- 9036103
TI  - [Acute, drug-induced tubulointerstitial nephritis].

PMID- 9036104
TI  - [Hantavirus-induced acute renal failure].

PMID- 9036105
TI  - [Tubulointerstitial kidney diseases in urinary tract infection, reflux and
      obstruction].

PMID- 9036106
TI  - [Tubulointerstitial kidney involvement in systemic diseases].

PMID- 9036107
TI  - [Nephrotoxin-induced tubulointerstitial nephropathies].

PMID- 9036108
TI  - [Analgesic nephropathy].

PMID- 9036109
TI  - [Uric acid and tubulointerstitial kidney diseases].

PMID- 9036110
TI  - [Interstitial involvement in glomerulonephritis].

PMID- 9036111
TI  - [Interstitial changes in kidney transplants].

PMID- 9036112
TI  - [50-year-old patient with leukocytoclastic vasculitis and arthralgia].

PMID- 9036113
TI  - [19-year-old patient with thromboembolism caused by oral contraception].

PMID- 9036115
TI  - [Request for pathophysiologic explanation of hypoxemic disorders (e.g. heart
      defect with right-left shunt, diseases with respiratory insufficiency) leading to
      clubbed fingers and toes and hour-glass nail manifestations].

PMID- 9036114
TI  - [Possible involvement of the autonomic nervous system in herpes zoster].

PMID- 9036116
TI  - [Heparin-induced thrombocytopenia].

PMID- 9036117
TI  - [18th European Cardiology Congress. Cardiology 200 years after discovery of
      digitalis glycosides. Birmingham/UK, 25-29 August 1996].

PMID- 9036118
TI  - [Memory disorders].

PMID- 9036119
TI  - Visceral leishmaniasis--an emerging zoonosis in the Jersalem area.

PMID- 9036120
TI  - [Immunologic aspects of infections with papillomaviruses. Prospects for a
      vaccine].
AB  - Human papillomaviruses induce benign or malignant epithelial proliferations in
      both skin or mucosa and are involved in the development of anogenital cancer. One
      can consider two approaches towards vaccine development: prevention of infection
      by prophylactic induction of virus neutralizing antibodies or therapeutic
      vaccination which would lead to regression of already existing lesions.
      Neutralizing antibodies are directed against 3-dimensional structures on intact
      virions. Such antibodies which are protective in model systems can be induced
      safely by DNA-free "virus-like-particles". These constructs are candidates for a
      prophylactic vaccine. A further approach to optimize the vaccination strategy
      concentrates on immunotherapy of precancerous or malignant lesions by induction
      of a specific cell-mediated immune response. Hypothetically the transforming
      papillomavirus proteins which are expressed in basal layers of the epidermis
      could be used as a therapeutic vaccine in the form of synthetic peptides.

PMID- 9036121
TI  - [Animal mite-induced epizoonoses and their significance in dermatology].
AB  - Different mite species may infest humans temporarily; such arthropods should be
      considered a possible cause of pruritic skin reactions of unclear origin. Pseudo
      scabies is a common problem. This self-limiting dermatosis may often be
      misdiagnosed. Several mite species including Sarcoptes scabiei var. canis,
      Sarcoptes scabiei var. bovis, Notoedres cati, Cheyletiella yasguri, Cheyletiella
      blakei, Dermanyssus gallinae and Ophionyssus natricis may infest human skin,
      causing symptoms. Other less common animal mites, Neotrombicula autumnalis and
      foodstuff mites are also discussed.

PMID- 9036122
TI  - [Plasmapheresis and immunopathogenetic aspects of toxic epidermal necrolysis].
AB  - Drug-induced toxic epidermal necrolysis (TEN) is a rare but frequently lethal
      disease of the skin and mucosa of unknown etiology. Toxic metabolic and
      immunologic products in the serum have been discussed as possible causes. For
      this reason we have performed plasmapheresis on these patients for many years.
      Results regarding survival and healing of the lesions are quite favorable, as
      exemplified with two patients described here who benefited from the procedure
      despite their old age. In order to gain insight into possible disease mechanisms
      that would explain the beneficial effect of plasmapheresis, we did
      immunohistochemical studies on these patients before and in one case after the
      procedure. In dermis and epidermis, there was a striking increase of macrophages
      and a relative increase of CD8-positive lymphocytes which might act as cytotoxic
      effector cells; these findings can be interpreted as the result of an
      immunological reaction. An increased staining of lesional epidermis with TNF
      alpha, as previously noted by other authors, should be interpreted with caution
      since necrotic cells are involved. On the basis of the clinical results, the
      pathogenetic considerations, and in view of the lack of specific treatment
      modalities, clinical studies concerning plasmapheresis for the treatment of toxic
      epidermal necrolysis are recommended, particularly since this procedure is widely
      available and generally well tolerated.

PMID- 9036123
TI  - ["Sentinel" lymphonodectomy with scintillation detector. A new strategy in
      treatment of malignant melanoma].
AB  - For decades the results of elective lymph node dissection (ELND) are differently
      discussed, so that it is not definitely recommended at present the less so since
      the morbidity of this operation can't be neglected. Since the beginning of 1995
      we practice a gamma-probe guided sentinel lymphonodectomy (SLNE) on patients with
      melanoma from a Breslow tumor thickness of 1 mm upward, after injecting a
      colloidal 99m-Tc labelled tin (II) - sulfide solution around the tumor or the
      scar, if the tumor has been excided before. By this method, that allows a
      selection of patients who according clinically to a stage I or II (UICC) but even
      histopathologically to a stage III and who are profiting of a removal of the
      regional lymph nodes, the sentinel node can be exactly localised, tissue-sparing
      removed at minimal complication rates and the completeness of the removal can be
      verified by measurements of the radioactivity. When finding metastases in the
      histopathological examination of the node a dissection of the whole region
      follows.

PMID- 9036124
TI  - [Neoplasms in nevus spilus].
AB  - Among 946 patients with nevus spilus we observed 5 patients (3 women and 2 men)
      with transformations on it-2 cases with malignant melanoma and 3 cases with spitz
      nevus. Histologically the nevus spilus is a superficial variant on congenital
      pigmented nevus missing corial parts. Because of the risk of transformation a
      regular skin examination is advisable, a prophylactical excision of nevi spili as
      used in congenital pigmented nevi should be discussed.

PMID- 9036125
TI  - [Cutaneous malacoplakia in a patient with psoriasis vulgaris].
AB  - A 58 year old patient suffering from psoriasis vulgaris had typical erythematous,
      scaly plaques for 20 years. In addition, an erosive, therapy-resistant plaque was
      found in the perianal region. A biopsy was taken to exclude malignancy; it showed
      intracytoplasmic Michaelis-Gutmann-bodies as a marker for malakoplakia, which
      rarely occurs in the skin. In further electron microscopic investigation,
      intracytoplasmatic bacteria could be demonstrated. An underlying malignancy or
      chronic renal insufficiency with immunosuppression were not found in this
      patient; both are often associated with malakoplakia.

PMID- 9036126
TI  - [Successful treatment of chronic discoid lupus erythematosus with argon laser].
AB  - We report on a patient with chronic discoid lupus erythematosus who was treated
      with argon-laser. The patient suffered from long-standing lesions and had been
      pretreated with various drugs; with no or slight improvement. After a few argon
      laser applications, the treated skin lesions improved dramatically while the
      untreated lesional skin showed continuous disease activity. Histological and
      immunohistological investigations of biopsies from treated and untreated lesional
      skin suggest that endothelial mechanisms play a role in the generation and
      maintenance of discoid lesions in lupus erythematosus. This is the first reported
      case of successful treatment of chronic discoid skin lesions of a lupus
      erythematosus patient with argon-laser.

PMID- 9036127
TI  - [Skin infections caused by Mycobacterium gordonae. Case report and review of the
      literature].
AB  - Mycobacterium gordonae is an atypical mycobacterium of very low pathogenic
      potential. It is widely distributed in soil and water and often detected on the
      mucous membranes of healthy persons. In recent years, there have been numerous
      reports of infections by M. gordonae in immunocompromised patients. In contrast,
      only four cases of skin infections by M. gordonae in immunocompetent patients
      have been published. We report on another patient without evidence of
      immunodeficiency who developed an atypical mycobacteriosis after a thorn injury
      during gardening. M. gordonae was isolated by tissue culture. The skin lesion
      cleared completely after treatment with doxycycline for three months.

PMID- 9036128
TI  - [Angiokeratoma corporis diffusum universale (Fabry disease)].
AB  - Fabry's disease (Angiokeratoma corporis diffusum) is a rare X-chromosome linked
      recessive disorder belonging to the group of sphingolipoidoses. The basic defect
      involves the gene encoding alpha-galactosidase. Because this enzyme is
      responsible for decomposition of glycosphingolipids, its deficiency results in
      their accumulation in endothelial and smooth muscle cells. With time, generalized
      angiokeratomas, paresthesias, renal and cardiac insufficiency and cerebrovascular
      complications develop. We report a patient who in addition to the well-described
      findings also showed unique nail fold capillary changes not described so far.
      Analysis of serum concentration of alpha-galactosidase identified three female
      heterozygous carriers in the patient's family.

PMID- 9036129
TI  - [Ficus benjamina allergy].
AB  - We report the case of a 48-year-old patient suffered from asthma and
      conjunctivitis caused by an immediate type allergy to weeping fig (Ficus
      benjamina). By RAST inhibition test we could demonstrate that IgE antibodies
      react with allergens of fig; however our patient tolerated figs in oral
      provocation test. Sensitization to latex proteins reported to be cross reactive
      to Ficus species was not found. Ficus benjamina allergens represent relevant
      indoor allergens. A standardized allergen extract for skin testing is not yet
      available. Allergen specific IgE is mostly found in patients with strongly
      positive prick test results using the native sap of the tree. In 12 of 64 latex
      allergic patients we found simultaneous sensitization to weeping fig, so that
      cros-sensitization has to been considered in patients with IgE-mediated
      sensitization to latex.

PMID- 9036130
TI  - [Gram-positive septic-toxic shock with bullae. Intraepidermal splitting as an
      indication of toxin effect].
AB  - A fourteen-year-old girl with acute otitis media died from gram positive sepsis
      and toxic shock despite intensive treatment. The definitive bacteriological
      results showed positive cultures for both S. aureus and S. pyogenes serotype A.
      In vitro the bacteria produced the bacterial superantigens TSST-1, enterotoxin A,
      enterotoxin C (S. aureus) and erythrogenic toxin C (S. pyogenes). The patient
      presented with large flaccid sterile bullae on her chest and arms as well as
      necrotizing fasciitis. Tzanck test showed keratinozytes without necrosis and no
      inflammatory cells. Frozen-section and conventional skin biopsy specimens
      revealed subcorneal intraepidermal cleavage. These cytological and histological
      findings are those of staphylococcal scalded skin syndrome (SSSS) and differ from
      bullous erysipelas or toxic epidermal necrolysis (TEN). Therefore bacterial
      exotoxins are most likely responsible for the intraepidermal blistering in our
      case just as in SSSS. Bullae are an unfavorable prognostic sign in gram positive
      toxic shock syndrome. Both Tzanck test and frozen-section biopsy are easy to
      perform and useful in the early and rapid recognition of gram positive bullous
      toxic shock syndrome.

PMID- 9036131
TI  - [Partner treatment in Bowen's papulosis?].

PMID- 9036132
TI  - [HIV-associated skin diseases. 1: Follow-up and epidemiology of HIV infection,
      pathogen-induced HIV-associated dermatoses].

PMID- 9036133
TI  - [New knowledge on the pathogenesis of chronic recurrent urticaria].

PMID- 9036134
TI  - [Update on the latex allergy topic].
AB  - Type I allergies to latex have become an increasing problem in occupational
      dermatology during the past few years, especially since at least 10% of health
      care workers are affected. In the Department of Dermatology, University Erlangen
      Nuremberg, a 12-fold increase in latex-allergic patients has been documented
      between 1989 and 1995 with a clear trend to more severe systemic manifestations
      (from 10.7% in 1989/ 1990 to 44% in 1994/1995). Among the water soluble proteins
      (molecular weights 2 to 200 kD) which may induce latex allergy, at least 5 are
      considered as main proteins with known primary structure. In addition some
      "marker' proteins seem to induce specific IgE antibodies in special risk groups
      (e.g. 46 kD-protein in medical professions, 14.6 kD- and 27 kD-proteins in
      children with spina bifida). Cross reactions between latex and several fruits
      (especially avocado, kiwi, banana and chestnut) in 60 to 70% of latex-allergic
      patients have to be taken into account when evaluating and counselling affected
      patients. Most important in prophylaxis is the complete change to powder-free
      latex gloves in medical institutions, since these gloves usually have a low
      protein content. Our listing of surgical and examination gloves according to
      their protein content (as measured by the modified Lowry- and High Pressure
      Liquid Chromatography method) should be a useful guideline for the choice of
      suitable gloves.

PMID- 9036135
TI  - [Photodynamic therapy at the threshold of clinical use in disseminated
      dermatoses].
AB  - Photodynamic therapy (PDT) involving the sequential administration of
      photosensitizing drugs and light has a successful record in the treatment of
      superficial tumors. Recent investigations document not only cytotoxicity but also
      immunomodulatory effects of PDT. Cell type as well as state of activation and
      differentiation are among the parameters influencing susceptibility to PDT, thus
      allowing targeting of selected cell (sub-)populations. In addition to lasers, non
      coherent light sources are also effective. These features, along with current
      clinical experience, suggest PDT as an interesting alternative to better
      established photochemotherapies in the treatment of widespread malignant and
      benign dermatoses.

PMID- 9036136
TI  - [The sodium lauryl sulfate test. A noninvasive functional evaluation of skin
      hypersensitivity].
AB  - The purpose of this study was to determine whether 24 hour patch testing with
      0.5% sodium lauryl sulphate (SLS) could reliably predict skin susceptibility to
      an irritant when compared with the alkali resistance test (ART), a widely used
      method employing sodium hydroxide. After having given informed consent, 40
      patients (age range from 20 to 60 years) with an active irritant contact
      dermatitis (ICD), 40 patients in whom ICD had cleared, as well as 40 healthy
      volunteers serving as controls were tested. The skin responses to SLS were
      assessed both visually and by measurement of transepidermal water loss (TEWL) as
      an indicator of stratum corneum integrity. SLS significantly increased the
      erythema scores and TEWL in patients with healed ICD, and the increase of TEWL
      was even more pronounced in patients with active ICD. By contrast, a decrease in
      alkali resistance was found in patients with active ICD only but not in patients
      with healed ICD. The data obtained indicate that the SLS test, unlike ART, may
      provide a non-invasive tool predicting a possible constitutional skin
      susceptibility or indicating a subclinically impaired epidermal barrier function.
      However, because of the relatively high interindividual variation, a cut-clear
      statement concerning the skin susceptibility cannot be made by this test. On the
      other hand, the ART seems only to be useful for following and documenting the
      healing period following ICD.

PMID- 9036137
TI  - [Dental materials--problem substances in allergologic diagnosis? I: Analysis of
      test results in patients with mouth mucosa/dental material problems].
AB  - Patch testing as a part of the diagnostic evaluation of patients suffering from
      oral mucosal complaints or with symptoms where dental materials are suspected to
      be the cause is hampered by numerous difficulties. The ingredients of denture
      materials as well as their liberation in the oral cavity are often unknown.
      Contact with many of the potential ingredients of denture materials can occur on
      other occasions, as well, thus making it difficult to find out where the patient
      has acquired his or her sensitization. The special morphological and
      immunological situation in the oral mucosa may produce tolerance of substances
      which evoke a positive patch test reaction on the skin of the back. This paper
      introduces the possible spectrum of allergens in these patients and discusses the
      difficulties in the assessment of the relevance of positive patch test reactions.
      From August 1992 to July 1994, 756 patients with complaints of the oral mucosa
      and/or suspected contact allergy to denture materials were patch tested in the
      departments of dermatology joining the Information Network of Departments of
      Dermatology in Germany (IVDK). Among these patients, women were overrepresented,
      while individuals with atopic dermatitis were underrepresented. The allergen
      spectrum included amalgam, mercury compounds, gold salts, palladium chloride and
      methyl methacrylate. However, the epidemiological value of these data is limited.
      A second part of this paper will review the various groups of allergens.

PMID- 9036138
TI  - [Dental materials--problem substances in allergologic diagnosis? II: Patch test
      diagnosis and relevance evaluation of selected dental material groups].
AB  - The problems in patch testing and relevance evaluation as well as the practical
      consequences are discussed for the most important groups of dental materials
      (DM). These include metal alloys: amalgam with a low allergy prevalence;
      palladium salts showing a high correlation with nickel allergy but a low one with
      metallic palladium or alloys; the widespread allergen nickel is most relevant
      when dealing with nickel containing DM-alloys that are not corrosionresistant;
      gold salts with widely differing test results and limited benefit to detect
      genuine gold intolerance. Among synthetic resins methylmethacrylate is the most
      important allergen because of the high frequency of exposition. With composite
      materials and other methacrylates, both cross reactions and active sensitization
      should be kept in mind. Relevant reactions due to additives are rare; positive
      benzoylperoxide tests should be interpreted very critically. A number of DM may
      contain allergens of the etheric oils-colophonium - Perubalsam group. DM should
      be tested with standardized methods only. As the dental consequences may be
      expensive, interpretation of such test results demands utmost care and special
      experience.

PMID- 9036139
TI  - [Development of squamous cell carcinoma in chronic anal eczema and therapeutic
      consequences].
AB  - We report two cases of chronic anal eczema. In one case a squamous cell carcinoma
      developed at the site of inflammation. This carcinoma was treated by wide local
      excision. The second case was treated in the same way for prophylactic reasons.
      These two cases demonstrate the importance of biopsies and surgical intervention
      when dealing with a therapy-resistant chronic anal eczema.

PMID- 9036140
TI  - [Amelanotic melanoma of the vulva simulating lichen sclerosus et atrophicus].
AB  - Malignant melanoma of the vulva is an uncommon disease. The amelanotic subtype is
      only rarely mentioned. We report a 60-year-old patient with a 6 month history of
      vulvar pruritus. Ivory lesions combined with erosions and fine "cigarette paper'
      like wrinkling were suspicious for lichen sclerosus et atrophicus. Histologically
      the diagnosis of an amelanotic malignant melanoma was made. Amelanotic melanoma
      may present with a wide variety of clinical features. Even in the uncommon
      location of the vulva, amelanotic melanoma should be suspected in any nonhealing
      nonpigmented lesion.

PMID- 9036141
TI  - [Keratosis palmoplantaris varians et punctata. Clinical variability of an single
      genetic defect?].
AB  - Palmoplantar keratodermia (PPK) varians and PPK punctata are considered different
      entities within the group of hereditary palmoplantar keratodermas. Keratosis
      punctata of the palmar creases constitutes a localized form of keratodermia
      palmoplantaris punctata. We describe a 31-year-old man exhibiting both nummular
      and papular keratoses on the soles, as well as small punctate keratoses confined
      to the palmar creases. In view of the co-occurrence of these two types of PPK,
      the question arises whether keratosis palmoplantaris of the varians and the
      punctate type represent distinct entities or represent variable manifestations of
      the same gene defect.

PMID- 9036142
TI  - [Nail-patella syndrome].
AB  - The nail-patella syndrome is an autosomal dominant trait characterized by
      abnormalities of the nails, patella and radial head, iliac crest and, in some
      cases, nephropathy. The genetic defect is localized on chromosome 9q34.1. The
      clinical features in affected individuals vary greatly. The nephropathy may
      progress to end-stage renal failure, leading to decreased life expectancy. We
      report a woman with bilateral hypoplastic thumbnails, who also had aplasia of
      both patellae and subluxation of the left elbow joint with hypoplasia of the
      radial head. The mother and the sister of the patient had similar changes and
      also suffered from nephropathy.

PMID- 9036143
TI  - [Postoperative infection with Mycobacterium chelonae].
AB  - A 70-year-old patient developed Mycobacterium chelonae infection at a donor vein
      graft site following cardiac bypass surgery. The infection presented as
      fibrinous, necrotic ulcerations in the scar area. Mycobacterium chelonae and
      mycobacterium fortuitum are atypical mycobacteria and have been described
      previously causing infections after injections or surgical procedures. Infection
      of donor vein graft site is a rare complication after cardiac surgery. As
      mycobacterium chelonae cannot be cultivated on normal culture media, delayed
      wound healing might be disinterpretated as a primary wound healing disorder.
      Treatment of atypical myobacteriosis includes antibiotics, local heat therapy and
      surgical excision. Clarithromycin is the antibiotic of choice. We obtained
      complete healing after two months of Clarithromycin treatment, combined with heat
      therapy.

PMID- 9036144
TI  - [Improvement in ichthyosis congenita after varicella infection].

PMID- 9036145
TI  - [Gynecomastia--uniform pathogenesis, multiple etiologies. Comment on the
      contribution by W. Krause and B. Splieth: Diseases of the male breast].

PMID- 9036146
TI  - [1st Otto Braun-Falco Alumni Lecture Tubigen 26 April 1996. K. Wolff: Prevention
      in dermatology].

PMID- 9036147
TI  - [Contact dermatitis. I].

PMID- 9036148
TI  - What is PDDNOS and how is it diagnosed? Pervasive Developmental Disorder Not
      Otherwise Specified.

PMID- 9036149
TI  - Clinical Developments in Alzheimer's Disease. Tucson, Arizona, February 14-17,
      1996. Proceedings of a symposium.

PMID- 9036150
TI  - Protein design: the choice of de novo sequences.

PMID- 9036151
TI  - A steady-state template model that describes the kinetics of fibrin-stimulated
      [Glu1]- and [Lys78]plasminogen activation by native tissue-type plasminogen
      activator and variants that lack either the finger or kringle-2 domain.
AB  - The kinetics of activation of both [Glu1]- and [Lys78]Plg(S741C-fluorescein by
      native (recombinant) tissue-type plasminogen activator and its deletion variants
      lacking either the finger or kringle-2 domain were measured by fluorescence
      within fully polymerized fibrin clots. The kinetics conform to the Michaelis
      Menten equation at any fixed fibrin concentration so long as the plasminogen
      concentration is expressed as either the free or fibrin-bound, but not the total.
      The apparent kcat and Km values both vary systematically with the concentration
      of fibrin. Competition kinetics disclosed an active site-dependent interaction
      between t-Pa and [Glu1]Plg(S741C-fluorescein) in the presence, but not the
      absence, of fibrin. A steady-state template model having the rate equation v/[A]o
      = kcat(app).[Plg]/(Km(app) + [Plg]) was derived and used to interpret the data.
      The model indicates that catalytic efficiency is determined by the stability of
      the ternary activator-fibrin-plasminogen complex rather than the binding of the
      activator or plasminogen to fibrin. This implies that efforts to improve the
      enzymatic properties of t-PA might be more fruitfully directed at enhancing the
      stability of the ternary complex rather than fibrin binding.

PMID- 9036152
TI  - Family reactions to restraints in an acute care setting.
AB  - 1. Families do not realize that a patient has a right to refuse restraints and
      that the family members have a voice in the decision-making process. 2. Families
      in general are interested in restraint issues but do not have information at
      their disposal. 3. Nursing staff should be encouraged to educate family members
      regarding restraints through open communication and printed material.

PMID- 9036153
TI  - Formulating treatment partnerships with patients and their families. A case
      study.
AB  - 1. A care environment, per se, can foster patient recovery and confidence that
      things will work out as well as can be expected when staff practices and explicit
      processes are patient-centered and adapted to developmental and individual needs.
      2. Separating more cognitively impaired from higher functioning patients and
      developing more specialized nursing teams affords a healing and restorative care
      environment, individualized care routines and specialty groups along with finely
      tuned patient/family education. 3. Organized staff education and mentoring
      programs combined with master scheduling enhances the continuity of patient
      centered practices and risk management protocols.

PMID- 9036154
TI  - Approaches to resident sexuality.

PMID- 9036155
TI  - Residential care for persons with dementia. Are codes and regulations protective
      or counter-productive?

PMID- 9036156
TI  - A house of comfort.

PMID- 9036157
TI  - Hospital nurses' views about physical restraint use with older patients.
AB  - 1. A survey of knowledge, practice and attitudes about physical restraints was
      completed by nursing staff (RN, LPN, CNA) from four hospitals. 2. Nurses from
      both geriatric and geropsychiatric units reported significantly more educational
      activities about restraint use than did nurses on medical units. 3. RNs had the
      highest knowledge scores (56%), but lacked specific information about the dangers
      associated with restraint use. 4. While education about restraints is important,
      staff need role models who can help them problem solve and examine alternatives
      to restraints.

PMID- 9036158
TI  - [Terminal care].

PMID- 9036160
TI  - [Terminal care. I. Topics. 2. Death with dignity and euthanasia].

PMID- 9036159
TI  - [Terminal care. I. Topics. 1. Informing the patient that he has a cancer].

PMID- 9036161
TI  - [Terminal care. I. Topics. 3. Limits in life-preserving care and advances in
      palliative treatment].

PMID- 9036162
TI  - [Terminal care. I. Topics. 4. Terminal care at home].

PMID- 9036163
TI  - [Terminal care. I. Topics. 5. Significance of informed consent].

PMID- 9036164
TI  - [Terminal care. I. Topics. 6. The role of a hospice].

PMID- 9036165
TI  - [Terminal care. II. Easing of symptoms of cancer patients. 1. Control of
      symptoms].

PMID- 9036166
TI  - [Terminal care. II. Easing of symptoms of cancer patients. 2. Methods of morphine
      administration].

PMID- 9036167
TI  - [Terminal care. II. Easing of symptoms of cancer patients. 3. Indications for and
      adverse effects of analgesics other than morphine].

PMID- 9036168
TI  - [Terminal care. II. Easing of symptoms of cancer patients. 4. Application of
      psychotropic agents].

PMID- 9036169
TI  - [Terminal care. II. Easing of symptoms of cancer patients. 5. Management of
      adverse effects of antineoplastic agents].

PMID- 9036171
TI  - [Terminal care. III. Practice of telling cancer patients the nature of their
      illness: a study based on questionnaires. 2. The status and future of the
      palliative care team].

PMID- 9036170
TI  - [Terminal care. III. Current practice in telling cancer patients the nature of
      their illness: a study by questionnaires. 1. Conditions at cancer hospitals].

PMID- 9036172
TI  - [Terminal care. III. The current status of informing cancer patients the nature
      of their illness: a study based on questionnaires. 3. The conditions at general
      hospitals].

PMID- 9036173
TI  - [The current status of terminal care: discussion].

PMID- 9036174
TI  - [Case of microscopic polyarteritis with a rise in the urinary IL-8 level].

PMID- 9036175
TI  - [Case of polyglandular autoimmune syndrome with Schmidt's syndrome complicated
      with Sjogren's syndrome].

PMID- 9036176
TI  - [Case of malignant pheochromocytoma with successful control of systemic
      metastasis with CVD chemotherapy].

PMID- 9036177
TI  - [Case of aortic occlusion caused by aortic dissection: recanalization by multiple
      fenestrations].

PMID- 9036178
TI  - [Case of coronary aneurysm associated with asymptomatic myocardial infarction of
      the inferior wall with sustained ventricular tachycardia as the major complaint].

PMID- 9036179
TI  - [Airway stenosis and stents].

PMID- 9036180
TI  - [Clinical application of thoracoscopy].

PMID- 9036181
TI  - [Usefulness of autopsy in clinical training in internal medicine: a report on
      "Survey on Feedback of Autopsy Findings to Clinical Training in Internal
      Medicine"].

PMID- 9036182
TI  - Bioactive amides from Glycosmis species.
AB  - Besides the known imide ritigalin (9), six new phenethyl/styrylamine-derived
      amides isolated from lipophilic leaf extracts of Glycosmis cf. mauritiana,
      Glycosmis cf. cyanocarpa, and Glycosmis crassifolia displayed pronounced
      antifungal and/or insecticidal activity against Cladosporium herbarum and
      Spodoptera littoralis, respectively, the methylthiocarbonic acid derivatives
      niranin (1), dehydroniranin A (2), and dehydroniranin B (3) as well as the
      isovaleric and senecioic acid derivatives thalebanin B (4), dehydrothalebanin B
      (5), and dehydrothalebanin A (6).

PMID- 9036184
TI  - [Key points in medical statistics--erroneous application of statistical methods.
      IV].

PMID- 9036183
TI  - Regioselectivity and substrate concentration-dependency of involvement of the
      CYP2D subfamily in oxidative metabolism of amitriptyline and nortriptyline in rat
      liver microsomes.
AB  - Kinetic analysis of the metabolism of amitriptyline and nortriptyline using liver
      microsomes from Wister rats showed that more than one enzyme was involved in each
      reaction except for monophasic amitriptyline N-demethylation. The Vmax values
      particularly in the high-affinity sites for E-10-hydroxylation of both drugs were
      larger than those for Z-10-hydroxylations. Their E- and E-10-hydroxylase
      activities in Dark-Agouti rats, which are deficient for CYP2D1, were
      significantly lower than those in Wistar rats at a lower substrate concentration
      (5 microM). The strain difference was reduced at a higher substrate concentration
      (500 microM). A similar but a smaller strain difference was also observed in
      nortriptyline N-demethylase activity, and a pronounced sex difference (male >
      female) was observed in N-demethylation of both drugs in Wistar and Dark-Agouti
      rats. The reactions with the strain difference were inhibited concentration
      dependently by sparteine, a substrate of the CYP2D subfamily, and an antibody
      against a CYP2D isoenzyme. The profiles of these decreased metabolic activities
      corresponded to that of the lower metabolic activities in Dark-Agouti rats. These
      results indicated that a cytochrome P450 isozyme in the CYP2D subfamily was
      involved in E- and Z-10-hydroxylations of amitriptyline and nortriptyline in rat
      liver microsomes as a major isozyme in a low substrate concentration range. It
      seems likely that the CYP2D enzyme contributes to nortriptyline N-demethylation.

PMID- 9036185
TI  - Fibromyalgia 20 years later; what have we really accomplished?

PMID- 9036187
TI  - [Is It possible to accomplish artificial heart within 10 years].

PMID- 9036186
TI  - Fibromyalgia 20 years later; what have we really accomplished?

PMID- 9036189
TI  - [Ideal clinical care system in thoracic surgery].

PMID- 9036188
TI  - [How far can heterologous transplantation progress?].

PMID- 9036190
TI  - [Thoracic surgery that is attractive to medical students].

PMID- 9036191
TI  - [Undergraduate and graduate education of thoracic surgery].

PMID- 9036192
TI  - [Contribution of molecular biology to surgical therapy of neoplasms].

PMID- 9036193
TI  - [Asian educational exchange in thoracic surgery].

PMID- 9036194
TI  - [Thoracic surgery and certification of the specialty].

PMID- 9036195
TI  - [Reality of thoracic surgery in Japan viewed from other countries].

PMID- 9036196
TI  - [Contribution of molecular biology to cardiovascular surgery].

PMID- 9036197
TI  - Roscoe R. Robinson: a festschrift.

PMID- 9036198
TI  - [Nabumetone, a new nonsteroidal antiinflammatory agent: clinical prospects].

PMID- 9036199
TI  - [Modern principles of drug therapy of peptic ulcer].

PMID- 9036200
TI  - [The evolution of th theory of chronic hepatitis: classification, nomenclature,
      diagnosis and treatment].

PMID- 9036202
TI  - [Quality of life of patients treated by hemodialysis].

PMID- 9036201
TI  - [Time organization of blood coagulation in patients with rheumatic heart disease
      involving circulation insufficiency].
AB  - Daily profiles of blood coagulation were studied in 20 normal subjects and 92
      patients with rheumatic heart disease with stages I-III circulatory insufficiency
      before and after traditional therapy and chronotherapy with heparin and curantyl
      added to traditional therapy with antirheumatic agents, diuretics, and cardiac
      glycosides. Time organization of the hemostasis was disordered in patients with
      decompensated heart disease, but it is possible to correct it by chronotherapy
      with heparin and curantyl.

PMID- 9036203
TI  - [Hemostasis disorders after resection of liver and approaches to their prevention
      and correction].
AB  - Second- or third-degree dysfunction of hepatocytes was the most frequent (47.9%)
      disorder in the hemostasis system on the first-second days after extensive
      resection of the liver, whereas after economic resection this disorder was
      observed in only 5.5% patients. Intraoperative blood loss of more than 3 liters
      is fraught with hemorrhages and hepatorenal insufficiency in the postoperative
      period. Such blood loss is complicated by coagulopathic states presenting as 1)
      hepatocyte dysfunction of the second-third degree, 2) hypoxia and decreased
      production of blood clotting factors, and 3) variants of the DIC syndrome. Study
      of the genesis of postoperative coagulopathies after resection of the liver and
      development of pathogenetically-based methods of drug correction, together with
      introduction of novel instrumental methods affecting the intensity of local and
      total hemostatic reaction, helped reduce 2.5 to 3 times the total blood loss.

PMID- 9036204
TI  - [Clinicoimmunological characteristics of aneurysmic lesion in nonspecific aortic
      arteritis].
AB  - The examination of 50 patients with nonspecific aortic arteritis (NAA) discovered
      that 14% of the patients had aneurysms. The latter occurred more frequently in
      the ascending aorta and manifest clinically as aortic regurgitation and angina
      pectoris. Immunological disorders were compared in NAA patients with stenotic and
      aneurysmic lesions (groups 1 and 2, respectively). In group 1 high IgE and CIC
      concentrations occurred more frequently suggesting the involvement of
      immunological abnormalities in genesis of aneurysms in NAA. Most of group I
      patients had disturbances of lipid metabolism indicated by elevated cholesterol
      level. The latter promoted development of atherosclerosis.

PMID- 9036205
TI  - [Reactive arthritis: terminology, etiology and pathogenesis].
AB  - Different serovars of Y. enterocolitica, Y. pseudotuberculosis, Acinetobacter
      calcoaceticus, and Pseudomonas pauimobilis were isolated from the synovial fluid
      of 23 out of 34 patients with Yersinia-triggered arthritis by a new
      bacteriological method based on the selection of the optimal conditions for
      microorganism culturing; in some cases the strains were isolated repeatedly. The
      authors discuss the necessity of correcting the previous notions on the aseptic
      nature of reactive arthritis.

PMID- 9036206
TI  - [On the problem of regulating the biological rhythms of the body].

PMID- 9036207
TI  - [Chronic insulin overdosage, hyperinsulinemia, atherosclerosis].
AB  - Biochemical and immunological indices were studied with regard to insulin dose in
      321 patients with diabetes mellitus type I. Overdosage of insulin in these
      patients induced significantly more frequently clinical manifestations of
      atherosclerosis, marked shifts in lipid spectrum of the serum and in
      immunological picture. In diabetics on physiological doses of insulin
      atherosclerosis is a rare finding, lipid spectrum and immunological indices in
      stable normoglycemia did not differ much from controls. Implication of chronic
      insulin overdosage in mechanism of atherosclerosis onset is suggested.

PMID- 9036208
TI  - [Genetic markers of the ABO blood system in pulmonary sarcoidosis patients of
      different ethnic origin].
AB  - Analysis of published data and investigations of their own permitted the authors
      to detect the relationship between the incidence of AB0 blood groups and the
      ethnic appurtenance. The 0(1) and A(II) blood groups were appreciably more
      incident in the Europeans, including the Russians, whereas in the Asians (Kazakhs
      et al.) the B(III) group prevailed. In the Russian sarcoidosis patients groups
      A(II), less frequently B(III) predominated. The clinical course of sarcoidosis is
      more benign in patients with the 0(I) group, the initial and first stages of the
      disease predominating. In patients with the A(II) group sarcoidosis runs an
      unfavorable course, with the second and third stages predominating, and hence,
      patients with this blood group should be singled out as the risk group.

PMID- 9036209
TI  - [Use of enzyme substitutes in hypolactasia].
AB  - The paper presents the results of clinical and laboratory studies of lactrase, a
      drug containing lactase. This agent is recommended for splitting lactic sugar in
      subjects with appreciably decreased production of endogenous lactase
      (hypolactasia). Twenty-eight patients with this condition were examined. Manifest
      clinical symptoms of the condition were observed after loading with 50 g of
      lactose in all examinees. Addition of 250 mg of lactrase to lactose led to
      complete clinical compensation of the deficit of endogenous lactase in 75%
      examinees, and if 500 mg of lactrase was administered, hypolactasia was
      compensated in virtually all patients. A single intake of 50 g of lactose with
      lactrase causes a statistically reliable increase of glycemia in such patients.
      Moreover, a reliable effect of lactrase was observed when measuring galactose in
      the urine following the lactose test with 250 and 500 mg of lactrase. Our results
      indicate a high efficacy of lactrase in the treatment of patients with
      hypolactasia.

PMID- 9036210
TI  - [Prospects of using computer expert system in the diagnosis of diseases of the
      respiratory system].

PMID- 9036211
TI  - [Effect of nimodipine in the diastolic function of the left ventricle in patients
      with essential hypertension and atherosclerotic circulatory encephalopathy].

PMID- 9036212
TI  - [A chronobiological approach to correcting disorders of time organization of
      clofelin hemodynamics in patients with stage II essential hypertension].
AB  - The efficacy of clofelin chronotherapy was assessed in 21 patients with stage II
      essential hypertension with due consideration for the circadian and circaseptan
      acrophase of arterial pressure (AP). AP and stroke volume were measured by
      tetrapolar chest rheography. Daily profiles of the major hemodynamic parameters
      were assessed at 8.00, 12.00, 16.00, 20.00, and 24.00 o'clock for 7 days prior to
      and 12 days after chronotherapy with clofelin in a single daily dose of 0.0375 to
      0.075 mg with due consideration for the circadian and circaseptan acrophase of
      AP. The circadian and circaseptan rhythm of the basic parameters of circulation
      was disordered before therapy. Clofelin administered 1.5 to 2 h before the
      acrophase of circadian and circaseptan rhythm of AP brought about a stable
      hypotensive effect and positive time course of clinical symptoms on day 4 of
      chronotherapy; in addition, it improved the chronostructure of the circadian
      rhythms of the major hemodynamic parameters.

PMID- 9036213
TI  - [Magnesium sulfate in management of bronchial asthma].
AB  - The effect of magnesium sulfate aerosol (osmolality of the solution 260 mmol/l,
      pH 6.6) on bronchial sensitivity and reactivity to acetylcholine (AC) and graded
      exercise as well as bronchial permeability measured by general plethysmography
      and pneumotaxography were evaluated in 49 patients with mild and moderate
      bronchial asthma (BA). When compared to placebo, magnesium sulfate (MS)
      inhalations performed at the stage of attenuating exacerbation, improved
      immediate and long-term response of patients with atopic and effort BA. In this
      disease, both single and course doses of MS reduced nonspecific bronchial
      hyperreactivity and secretory activity of mast cells. A positive trend in the
      parameters of AC provocative test predicted efficacy of MS treatment in the
      majority of BA sufferers.

PMID- 9036215
TI  - [Extrapulmonary manifestation of sarcoidosis].

PMID- 9036214
TI  - [Aminostigmine-a novel drug against home poisoning].
AB  - Aminostigmin, a novel reversible inhibitor of cholinesterase developed in Russia,
      has been tried in management of poisoning with cholinolytyics, antihistamine
      drugs, tricycle antidepressants and derivatives of 1,4-benzodiazepine. The
      treatment of 144 patients with aminostigmin and 20 patients with galantamin
      showed close to similar efficacy of these drugs. The scheme of aminostigmin
      administration is proposed warranting fast relief of cholinolytic syndrome in
      subjects poisoned with cholinolytics, antihistamine drugs and antidepressants.
      Benzodiazepines poisoning was unresponsive to aminostigmin. Rare side effects
      were caused by overdose. Aminostigmin is an effective antidote in cholinolytic
      poisoning.

PMID- 9036216
TI  - [Dyspnea].

PMID- 9036217
TI  - [Primary multiple carcinoids of the small intestine].

PMID- 9036218
TI  - [A rare combination of enteric diphtheria and dysentery].

PMID- 9036220
TI  - [Leukopenia in patients with acute pneumonia].

PMID- 9036219
TI  - [Immunomodulators and some aspects of their clinical use].

PMID- 9036221
TI  - [Clinical and morphological analysis of long-term fasting as self-therapy with
      lethal outcome].

PMID- 9036222
TI  - [Comments on MA Nogaller's response to my paper "On the So-Called Functional
      Diseases"].

PMID- 9036223
TI  - [Functional diseases: a pediatrician's view-point].

PMID- 9036225
TI  - [From reports to nursing visits].

PMID- 9036224
TI  - [Family doctor: what he or she is to know in Russia].

PMID- 9036226
TI  - [Decubitus ulcers--how to measure the risks].

PMID- 9036227
TI  - [Ethical principles and how to live them. Nursing research and the ethical
      challenge].

PMID- 9036228
TI  - [How male nurses see their female colleagues].

PMID- 9036229
TI  - [In our hands: power].

PMID- 9036230
TI  - [A woman talks about her experiences. Power is not a taboo].

PMID- 9036231
TI  - [Scientific preparation of candidates for the health professions. Producing
      perfect actors].

PMID- 9036232
TI  - [Let us talk again about the student statute].

PMID- 9036233
TI  - [The nurse as conductor].

PMID- 9036234
TI  - [Patient transmittal report directly at the bedside].

PMID- 9036235
TI  - [Caring about humaneness].

PMID- 9036236
TI  - [To care humanely and professionally. AIDS: accompaniment and support].

PMID- 9036237
TI  - [Even the twelvth child is precious].

PMID- 9036238
TI  - [Cerebral proton spectroscopy of people infected with the human immunodeficiency
      virus].
AB  - BACKGROUND: This article presents a combined magnetic resonance imaging and
      proton spectroscopy protocol (MRI/1H-MRS) applied to study the brain of human
      immunodeficiency virus (HIV) infected patients. The spectroscopic results were
      compared with clinical and radiological parameters. PATIENTS AND METHODS: The
      proton spectra of 57 HIV patients and 20 control subjects were obtained from a
      volume of interest of 8 cm3 located in the parietooccipital region of the brain
      that did not include any focal lesion. The resonance areas due to N-acetyl
      aspartate (NAA), creatine (Cr) and choline (Cho) were obtained. The MRI exam
      allowed us to determine the presence of focal or diffuse lesions and the degree
      of atrophy. Finally, the clinical exploration included the performance of a Mini
      Mental test. The NAA/Cr, NAA/Cho and Cho/Cr ratios were correlated with clinical
      characteristics, the result of the Mini-Mental test, the presence of lesions and
      the degree of atrophy. RESULTS: There were altered spectral patterns in a volume
      of the brain that did not contain any focal lesion. The decrease in the NAA/Cr or
      NAA/Cho ratios was significative when considering the presence of atrophy, the
      existence of signs of cognitive deficiencies or the diagnosis of AIDS-dementia
      complex. CONCLUSIONS: The spectral changes found in the present study suggest the
      existence of neuronal lesions that would be due to the HIV-infection. A combined
      MRI/1H-MRS study may provide a more complete information about the neurological
      impairment by HIV and could constitute a marker of AIDS-dementia complex.

PMID- 9036239
TI  - [Lipoprotein profile in children and adolescents of the Autonomous Community of
      Madrid].
AB  - BACKGROUND: The aim of study was to know the lipoproteins distribution in
      children and adolescents from the Autonomous Community of Madrid, Spain, and to
      compare with other studies. MATERIAL AND METHODS: The sample included 3,635
      children and adolescents (1,853 males and 1,782 females), 4 to 18 years of age.
      We measured total cholesterol and triglyceride levels with enzymatic methods, the
      HDL-cholesterol concentration in the supernatant after precipitation of the rest
      of the lipoproteins, and LDL-cholesterol concentrations were calculated by
      Friedewald formula. RESULTS: Total cholesterol levels were 174 +/- 25 mg/dl (4.50
      +/- 0.64 mmol/l), triglycerides 60 +/- 24 mg/dl (0.67 +/- 0.28 mmol/l), LDL
      cholesterol 100 +/- 22 mg/dl (2.59 +/- 0.58 mmol/l), HDL-cholesterol 61 +/- 13
      mg/dl (1.6 +/- 0.34 mmol/l). 19.23% of the children studied had cholesterol
      levels above 200 mg/dl (> 5.18 mmol/l), and 41.5% of them had levels higher than
      180 mg/dl (> 4.66 mmol/l). CONCLUSIONS: The cholesterol levels as well as the HDL
      cholesterol levels in the student population of Madrid, Spain, were higher when
      compared to other studies. Less variation was found in the LDL-cholesterol
      concentrations.

PMID- 9036240
TI  - [Presence of markers predictive of type I pre-diabetes mellitus status in
      relatives of patients with type I diabetes mellitus].
AB  - BACKGROUND: The aim of this study was to analyze the predictive factors of IDDM
      in first degree relatives of IDDM patients. SUBJECTS AND METHODS: From 1992 to
      1994, 1,053 first degree relatives were screened for measuring islet cell
      antibodies (ICA) by indirect immunofluorescence (iFl). In all ICA positive
      subjects, beta cell function was analyzed by intravenous glucose tolerance test
      (IVGTT) and other immunologic parameters were also studied: anti-insulin
      antibodies (IAA) by radiobinding and antibodies to glutamic acid decarboxylase
      (GADAb) by ELISA methods. RESULTS: ICA were found in 3.1% of the first degree
      relatives. IVGTT showed a significant decrease in acute first phase of insulin
      response to glucose (IRI 1 minute + 3 minute) in those with ICA > or = 20 JDF
      units. In patients with ICA > or = 20 JDF units, 20% were found to be positive
      for IAA and 40% were positive for GAdAb. Thirty-one percent (10/32) of ICA
      positive first degree relatives fulfilled prediabetes criteria. During follow-up,
      40% (4/10) of these prediabetic patients developed IDDM. CONCLUSION: This study
      confirms the possibility of identifying among first degree relatives of IDDM
      patients the subgroup with high risk of developing IDDM thus allowing the
      initiation of therapy for preventing or delaying IDDM onset.

PMID- 9036241
TI  - [The future of pharmacologic surveillance in Spain: the need to join efforts].

PMID- 9036242
TI  - [Evidence-based medicine: trying to approximate science to the art of clinical
      practice].

PMID- 9036243
TI  - [Hereditary predisposition to breast cancer: assessment of genetic risk and
      recommendations for the clinical follow-up of high-risk cases].

PMID- 9036244
TI  - [Pleural effusion and mediastinal mass in a 21-year-old male].

PMID- 9036245
TI  - [Changes in liver function tests during intensive prolonged exercise].

PMID- 9036246
TI  - [Chronic idiopathic pachymeningitis associated with temporal arteritis. A case
      study].

PMID- 9036247
TI  - [Pseudomonas aeruginosa infection in patients infected with HIV admitted at a
      hospital unit for prisoners].

PMID- 9036248
TI  - [Quiescent multiple myeloma and HIV infection: coincidence or association?].

PMID- 9036249
TI  - [Acarbose-induced ageusia].

PMID- 9036250
TI  - [In favor of a limitless infectious disease specialty].

PMID- 9036251
TI  - [The main causes of death in Spain, 1992; comment].
AB  - BACKGROUND: To study the mortality from the leading causes of death in Spain in
      1992 and trends since 1980. POPULATION AND METHOD: The number of deaths was
      obtained from mortality statistics. We included the 12 causes with the highest
      mortality rates in 1992 and calculated for each cause of death the age adjusted
      mortality rates for each year in the study period, the percent change from 1990
      to 1992 and from 1980 to 1992, and the adjusted ratio of rates between men and
      women in 1992. RESULTS: The leading causes of death in 1992 were malignant
      neoplasms, with 24.3% of deaths and a mortality rate of 205.6 per 100,000
      population; diseases of the heart, with 22.6% and a rate of 191.8 per 100,000;
      and cerebrovascular disease, with 12.7% and a rate of 107.6 per 100,000
      population. Between 1980 and 1992 the adjusted mortality rate increased for four
      causes of death: malignant neoplasms; chronic obstructive pulmonary disease and
      similar diseases; nephritis, nephrotic syndrome and nephrosis; and suicide. From
      1990 to 1992, the adjusted mortality rate declined for all other causes of death.
      From 1990 to 1992, the adjusted mortality rate declined for all causes of death
      except for malignant neoplasms and human immunodeficiency virus (HIV) infection,
      which rose 0.4% and 69%, respectively. The adjusted mortality rate was higher in
      men than in women for all causes of death except for diabetes mellitus and
      atherosclerosis. CONCLUSIONS: Except for malignant neoplasms and HIV infection,
      mortality from all other leading causes of death declined in 1992 with respect to
      1990, independently of the trend experienced by each cause of death in the
      eighties.

PMID- 9036252
TI  - [Food and nutrient consumption in Spain in 1940-1988 (and II). Comparative study
      of the main sources of information on food consumption].
AB  - BACKGROUND: This paper has two objectives. The first is to examine the
      consistency of the main nutritional studies carried out in Spain over the last
      fifty years. The second is to use these studies to describe the changes in the
      Spanish diet over this period and to characterize the present dietary pattern.
      MATERIAL AND METHODS: We have used three types of studies. First, food balance
      sheets elaborated by Barbancho, FAO, OECD and the Department of Agriculture.
      Second, surveys on the foods purchased by population groups, in particular the
      household budget surveys, and the "panel de consumo alimentario" from the
      Department of Agriculture. Third, food consumption surveys from Catalonia, Vasque
      Country, Murcia, Madrid, and Reus. RESULTS: Protein, lipid and total caloric
      intake have increased over the last fifty years. Carbohydrate intake has been
      stable. Caloric intake from lipids has increased, caloric intake from protein has
      been stable and that from carbohydrates has decreased. All studies are consistent
      in that, from 1980 onwards, caloric intake from protein has been 12.5-16.7%,
      caloric intake from carbohydrates has been 39.3-48.1%, and that from lipids has
      been 36.6-46.0%. The monounsaturated/saturated ratio has been 1.2-1.7 and the
      polyunsaturated/saturated ratio 0.4-0.7. All data sources show a high consumption
      of foods typical of the Mediterranean diet, in particular fruit, vegetables, fish
      and vegetable oil, rich in unsaturated fats. Consistency among data sources is
      higher when data are expressed as percentage of total caloric intake than when
      they are expelled in absolute quantities. CONCLUSIONS: All data sources suggest
      that the Spanish diet has changed with the economic development, but it still
      keeps most of the characteristics of the Mediterranean diet.

PMID- 9036253
TI  - [Analysis of the diagnostic delay in tuberculosis].
AB  - OBJECTIVE: To identify the situations that influence in the delayed diagnosis of
      tuberculosis. PATIENTS AND METHOD: We studied 109 patients (87 non HIV-infected
      and 22 HIV-infected) who were diagnosed of tuberculosis in one year
      consecutively, using a questionnaire to obtain time intervals in which the whole
      diagnostic delay (WD) was divided. RESULTS: WD was higher than 1 month in 90 % of
      non HIV-infected patients. The delay due to the health system (SD) was higher
      (71% > 1 month) than the delay due to patient (PD; 30% > 1 month) and there was a
      negative correlation between both (R-0.73). In HIV+ group, WD was lower (59.1% >
      month) and, although PD was higher (40.9% > 1 month), the time that the system
      delayed the suspicion of the diagnosis was lower (5.5% > 1 month). In HIV-group
      there were the following significant differences: higher delay in the suspicion
      of diagnosis (DSD) (61.4% and 60.8% > 1 month) and shorter time to make the
      diagnosis (12.3% and 21.6% > 1 month) in sputum smear-positive patients and who
      had cavitary lesions; PD was higher (67.1% > 1 month) in patients with general
      symptoms and nearly none in patients with upper airways symptoms; and higher DSD
      in presence of nonspecific symptoms like cough or/and expectoration (68.6% > 1
      month) or upper airways symptoms (100% > 1 month). As these clinical symptoms
      were consulted in primary care mainly, there was a higher SD (75.75 > 1 month)
      and DSD (58.1% > 1 month), and were increased when a promptly chest X-ray was not
      performed (87.1 and 68.7% > 1 month). CONCLUSIONS: Delayed diagnosis of
      tuberculosis is common. In non HIV-infected patients, it occurs mainly in the
      health system. Diagnostic delays contribute to raise advanced disease with more
      contagious potential.

PMID- 9036254
TI  - [Mortality trends in Spain].

PMID- 9036255
TI  - [Clinical significance of the genetic variability of the human immunodeficiency
      virus].

PMID- 9036256
TI  - [Hypophosphatasia in adults. Report of 3 cases].
AB  - Three adult members of the same family with hypophosphatasia are described. Two
      of them, aged 23 and 24 yr, developed vertebral and peripheral fractures having
      low bone mass values and histological findings of trabecular and cortical
      osteoporosis with mild mineralization defects. In these two cases, the
      corticosteroid treatment received may have play role in the development of the
      symptomatic clinical picture because the third affected member of the family did
      not have bone mass abnormalities suffering only from early loss of teeth. Even
      though adult hypophosphatasia is a rare and oligosymptomatic disease, some risk
      factors may induce the development of osteoporosis with bone fractures.

PMID- 9036257
TI  - [Exploratory-confirmative perspective in biomedical applications of statistics: 2
      dialogues (I). Bayesianism versus frequentialism: their respective practical
      implications on data analysis].

PMID- 9036258
TI  - [Oral antibiotic treatment of chronic osteomyelitis in adults].

PMID- 9036259
TI  - [Provocation test with corticotropin liberating hormone in pregnancy].

PMID- 9036260
TI  - [Coffee drinking and blood cholesterol: a relationship or a confusion?].

PMID- 9036261
TI  - [Coffee and cholesterol].

PMID- 9036262
TI  - [Interdisciplinary functional units of geriatrics at general hospitals. Function
      and analysis of their effectiveness].

PMID- 9036263
TI  - [Postgraduate education through the MIR].

PMID- 9036264
TI  - No early rejection of animal organs in UK.

PMID- 9036265
TI  - Artificial lungs on the way--but don't hold your breath.

PMID- 9036266
TI  - Counseling parents of extremely premature babies.

PMID- 9036267
TI  - [Heart failure: oxidative stress and apoptosis].

PMID- 9036268
TI  - [Urinary incontinence. Various forms and therapeutic consequences].

PMID- 9036269
TI  - [Anal fissure. Possibilities for treatment].

PMID- 9036270
TI  - [Functional dyspepsia. Treatment of gastrointestinal diseases].

PMID- 9036271
TI  - [Laxatives in chronic constipation].

PMID- 9036272
TI  - [Solanum dulcamara L.--a "plant cortisone"?].

PMID- 9036273
TI  - [The use of radioisotope labelling for studying the feeding of sandflies
      (Phlebotominae) and their move into colonies of the greater gerbil (Rhombomys
      opimus Licht.)].
AB  - The fly off and distribution of sandflies, vectors of zoonotic cutaneous
      leishmaniasis after meal on great gerbils were studied by means of radioisotope
      techniques. The experiments were carried out near the town of Mubarek
      (Uzbekistan). Three Rhombomys opimus were marked by intraperitoneal injection of
      14C-glycine solution. Then they were allowed to come back to their burrows. The
      sandflies were radioactively labelled during bloodsucking on the rodents. Fifty
      seven labeled female sandflies were caught on the surface of burrows with the
      marked R. opimus and on 5 colony burrows at a distance of 70-280 m from it for 6
      nights. Seventeen females were Phlebotomus papatasi (0.9% of all the caught
      females of this species) and 40 females belonged to the Paraphlebotomus subgenus
      (7.0%). The fly off occurred both before and against the wind. The labeled
      females were found on all burrows where sticky papers were placed, but their
      density was 16 times lower at a distance of 280 m than in the burrow colony of
      their release.

PMID- 9036274
TI  - [Infections of the Lyme borreliosis group--ixodid tick-borne borrelioses in
      Russia].
AB  - The universally accepted terms Lyme disease of Lyme borreliosis actually apply to
      the whole group of etiologically independent diseases. This group of diseases is
      designated as ixodid tick-borne borrelioses (ITBB) in contrast to argasid tick
      borne borrelioses (ATBB) associated with soft ticks. Analysis of individual,
      etiologically specific diseases should be the matter of strategy in researches
      and diagnostic studies of ITBB. The prevalence of B. garinii and B. afzelii in
      the greater part of Eurasia is now beyond doubt. To date, ITBB cases have been
      registered in 46 of 50 Russian regions inhabited by I. persulcatus and I. ricinus
      ticks. Therefore, a considerable or even a great part of the world range of
      infections currently collectively called Lyme disease (LD) is located on the
      territory of Russia. The mean ITBB incidence rates in 1993-1994 was 3.1 per
      100,00 inhabitants. Data reflect a considerable progress in ITBB diagnosis, made
      in the past two or three years rather than an increase in morbidity rates. The
      greatest incidence of ITBB is registered in the Ural and west Siberian regions
      (27 and 17.2%, respectively). In the following years, provided IBBT diagnosis and
      surveillance are properly organized, the eastern regions of Russia would account
      for the highest ITBB morbidity. Prognosis is that at least 10,000 to 12,000 new
      ITBB cases may be annually detected in Russia. ITBB affects mainly adult able
      bodied persons. However, in 1993-1994 children under 14 years of age accounted
      for 1.4% of the total number of cases in Russia. On the whole, the proportion of
      city dwellers among ITBB patients was 84%, amounting to as high as 90-94% in some
      regions. The mean ITBB morbidity rate for the rural population in 1993-1994 was
      1.8 per 100,000 inhabitants. In 1993-1994 IFA was regularly performed only in 21
      regions. Analysis of paired serum samples obtained from suspected ITBB patients
      in due time yielded positive results in 65-70% of cases. To identify fresh ITBB
      cases more thoroughly, at least 200,000 persons should undergo serological
      testing every year. This number is approximately 25 times greater than the actual
      number of these tests annually performed in Russia. In this connection, IFA will
      retain for several years its contribution to a conventional laboratory test
      routinely used in Russia.

PMID- 9036275
TI  - [Nervous system lesions in patients with ixodid tick-borne borreliosis].
AB  - Previous studies indicated that in the Perm Region there are two pathogen
      species: B. garinii and B. afzelii which cause the disease mainly with
      neurological and dermatological manifestations. In 1990-1994, in the Perm Region
      646 patients with Ixodes tick-borne borreliosis (ITBB), including 535 with
      erythema migrans, 54 without it, and 57 with late chronic disease were studied.
      Damages to the central and peripheral nervous systems were detected at all stages
      of an infectious process. The prevalent clinical manifestations are encephalitis,
      encephalomyeloradiculoneuropathies, mono- and polyneuropathies. These
      abnormalities are more frequently formed in patients with its erythema-free type
      both in the acute period of the disease and in the late period of infection. A
      varying spectrum of neurological syndromes and their significant incidence
      determine the resemblance of ITBB in Russia and West Europe. The clinical
      findings are in good agreement with the results of etiological structural studies
      of ITBB in the region.

PMID- 9036276
TI  - [The reaction of taiga ticks to an attractant. III. The use of attractant
      acaricidal granules in a field experiment].
AB  - On June 15, a total of 300 granules were placed at 1-m intervals on the sides of
      a concrete-covered road located along the steep slope of a valley. The number of
      ticks on 300-m plots decreased from 557 (before the experiment) to 55 on June 24
      and to 11 on June 27. On the 200-m control plot there were 256, 280 and 168
      ticks, respectively, in the same periods of time. Thus, the efficiency of tick
      eradication was 91 and 97% on days 9 and 12, respectively.

PMID- 9036277
TI  - [The distribution of tick-borne encephalitis virus-infected ticks along a linear
      census route].
AB  - An individual study of Ixodes persulcatus Schulze, 1930, established that the
      distribution of infected ticks differs from the normal distribution and it is
      most close to the Poisson distribution. There is a tendency to deviation from the
      uniform-random distribution associated with higher infected tick contact rates in
      some parts of the route.

PMID- 9036278
TI  - [The characteristics of diphyllobothriasis foci in the Pur River basin (Yamalo
      Nenets Autonomous Okrug)].
AB  - Diphyllobothriases are spread in the population of the Pur River basin unevenly.
      The population on the lower Pur is affected little, but that on the upper Pur and
      its tributaries is affected much more. This is largely accounted for by what
      fishes are prevalent in the diet of the local population and how they consume
      fish. In the past 30 years, the infection of fish with Diphyllobothrium latum
      larvae and the prevalence of the population's infection have reduced in some
      areas of the Pur River basin. Among other things, this is associated with man
      made impacts on the local water reservoirs (development of areas, gas extraction,
      etc.), which influences the first and second intermediate D.latum hosts.

PMID- 9036279
TI  - [The multiyear changes in the epidemic activity of the foci of zoonotic cutaneous
      leishmaniasis at the Murgab oasis. I. An analysis of the relations of morbidity
      to heliogeophysical factors].
AB  - Attempts were made to analyse the relationships of changes in the pattern of
      zoonotic cutaneous leishmaniasis (ZCL) morbidity by the 1951-1993 statistics of
      the Turkmenistan Ministry of Health by the areas of Maryiskii velaiat with
      heliogeophysical factors. For quantitative characterization of solar activity
      changes, various indices were used; among them there was the Wolf number, radio
      radiation flux at a wavelength of 10.7 cm. and the geomagnetic Aa-index. In some
      many-year observations, vague cyclic variations were detected on a personal
      computer by spectral and periodogram analyses proved to be effective in other
      diseases. Correlation and cross-correlation analyses were used to evaluate the
      possible relationships between the morbidity rates and the changes in
      heliogeophysical factors. The study has revealed that the epidemic activity of
      ZCL foci is characterized by cyclicity with variations of about 2.4, 3.6, 6.9,
      and 11.2 years. The changes in ZCL morbidity in the areas, including the natural
      ZCL foci of Murgab delta landscapes, slightly differ from those in the areas with
      valley foci in the south part of the velayat in the duration and expression of
      cycles. At the same time sun-caused 11-year cycles are observed in all groups of
      the areas, though they are slightly more pronounced in the north than in the
      south. The greatest epidemic outbreaks (1956-1957, 1965, 1977, and 1986-1988)
      occurred in various areas of the Murgab oasis on an average of 1-3 years after
      the minimum of 11-year solar cycles. Noteworthy, they are greatly marked in odd
      solar activity cycles (the 1957 and 1977 outbreaks) in many areas. Among the
      parameters chosen, the radio flux of solar radiation at a wavelenght of 10.7 cm
      and the Wolf number (the correlation coefficients are as high as 0.30-0.50 at P =
      0.95) are closely related with ZCL morbidity changes when the plot is shifted. At
      the same time the values of the geomagnetic Aa-index are unlikely to greatly
      affect changes in the epidemiological situation. The regularities revealed are of
      particular significance for long-term prediction of the greatest rises of ZCL
      morbidity rates. Taking into account the estimated solar activity changes within
      the next years, one may expect activation of natural ZCL foci and, in case of
      untimely use of prophylactic measures, the following rise in the population's
      morbidity in 1998-1999.

PMID- 9036280
TI  - [The species classification of the causative agent of human diphyllobothriasis in
      the area of the Pacific coast of Russia].

PMID- 9036281
TI  - [The primary and secondary prevention of enterobiasis today].
AB  - The paper provides evidence for dividing the prevention of enterobiasis, which is
      the major human helminthiasis in Russia, into social and medical ones. It
      proposes to implement 4 directions of medical prophylaxis: behavioral, sanitary
      and hygienic, functional and biological, and therapeutic and health-improving
      actions. The paper also characterizes measures underlying each of them.

PMID- 9036282
TI  - [The search for new antiparasitic agents. 17. The synthesis and study of the anti
      echinococcal activity of the new preparation G-1697].
AB  - The paper describes the synthesis of the new agent G-1697 which is 4-[(benzo
      2,1,3-thiadiazolyl-4)amino]-5, 6,7,8-tetrahydrobenzothieno [2,3-d] pyrimidine and
      the results of testing its acute toxicity and antiparasitic activity on a model
      of Echinococcus multilocularis invasion at the larval stage in cotton rats. The
      maximum nonlethal dose of G-1697 was 4.0 g/kg for outbred mice of both sexes
      whose weight was 14-16 g. Adult cotton rats (males) received the agent with their
      feed in increasing daily doses for 3 weeks continuously on days 8 to 28 after
      infection. The daily dose of its active ingredient varied from 0.03 to 0.35 g/kg
      and averaged 0.12 g/kg (the mean total dose per session was 2.47 g/kg). The
      baseline weight of parasitic larvocysts (PL) per animal averaged 0.28 g at the
      baseline. In the treated and control rats sacrificed 34 days following infection,
      the mean mass of PL per animal was 0.95 and 7.51 g, respectively. In the cotton
      rats treated with G-1697, the suppressed growth index calculated by three
      parameters (moderate, maximum, and minimum mass of PL in the animals of the
      comparable groups after treatment with regard to the similar baseline variables)
      was 90.8, 91.0 and 92.7, respectively, versus the controls. Among all PL found in
      each animal, its death was approximately 70-90% in the treated rats.

PMID- 9036283
TI  - [The results of an experimental study of an anti-Opisthorchis preparation made
      from plant raw material].
AB  - Agents and biologically active fractions derived from medical plants grown in
      Siberia were tested in vitro and in vivo. The extract from the aspen bark
      displayed the highest antiopisthorchiatic activity. This agent given at a
      concentration of 10(-3) caused 100% death of Opisthorchis 72 hours later. In
      golden hamster experiments, the efficiency of the aspen bark extract was 73.48
      83.0%. Butanolic and ethylacetatic extracts were found to have the greatest
      antiopisthorchiatic activity. The results of chemical and chromatographic studies
      indicated that active fractions contained salicine and its derivatives. The aspen
      bark extract produces no substantial toxic effect on laboratory animals and
      belongs to the class "Low-toxic substances".

PMID- 9036284
TI  - [The prevalence of hydatid disease among the population of the Republic of
      Bashkortostan].

PMID- 9036285
TI  - [The antigenic differentiation of hantaviruses by using monoclonal antibodies].
AB  - 85 hantavirus (HV) strains from Russia and other counties were examined by
      indirect fluorescent antibody test using monoclonal antibodies (MAbs) prepared
      against hantaviruses: Hantaan (Hantaan 76-118, A-9 strains), Seoul (SR-1, R-22
      strains) and Puumala (Hallnas 83-223 strain). 68 HV strains were differentiated
      into five virus type groups: Hantaan, Puumala, Seoul, Prospect Hill and Belgrade
      Dobrava. 17 strains were found to be antigenically closely related but distinct
      from Hantaan type (4 strains), Puumala (6 strains) and Prospect Hill (7 strains).
      The antigenic characteristics of these 17 strains suggested two supplementary
      antigenic subgroups of the Hantaan, two of Puumala and two of Prospect Hill.

PMID- 9036286
TI  - [The practical value for medical parasitologists of the published papers in the
      journal Meditsinskaia parazitologiia i parazitarnye bolezni over 1987-1990].

PMID- 9036287
TI  - [The organization of the control of taeniarhynchiasis in Bukhara Province].
AB  - The Bukhara Province occupies the third place after the Khorezm Province and
      Karakalpakstan in the incidence of taeniarhynchiasis. In 1993, the Republic
      notifies 2608 (0.05%) patients with taeniarhynchiasis, including 215 (0.06%)
      patients in the Bukhara Province. Sanitation measures resulted in reduced
      incidence of the disease by 4.8 times in the region and by over 50 times (to
      0.05%) in the Romitan District. The morbidity rate of the population tends to be
      stable.

PMID- 9036288
TI  - [The results of micromorphological and histochemical studies of the
      musculocutaneous sac of nematodes in the suborder Oxyurata after anthelmintic
      exposure].
AB  - The paper presents the results of studies of the effects of anthelminthic agents
      on the in tegumentary tissues of nematodes from the Oxyurata suborder. All used
      anthelmintics causes varying structural changes in the integumentary tissues of
      Oxyurata. At the same time, there is swelling and loosening of the cuticle, its
      detachment from the subcuticular layer, vacuolization of the hypodermis and the
      plasma part of muscular cells, as well as irreversible changes in the cellular
      organoids of the hypodermis and muscular cells (destruction of canals of the
      endoplasmic network and the Golgi apparatus, mitochondrial membrane damage,
      nuclear pyknosis or lysis etc.)

PMID- 9036289
TI  - [The characteristics of cryptosporidiosis epidemiology in the European part of
      Russia].
AB  - Large-scale surveys of representative population groups (n = 2243) in 7 cities
      and 3 provinces of the central, Povolzh'e, and northwestern regions of the
      Russian Federation provided the basic epidemiological features of
      cryptosporidiosis in the European part of the country. Its mean incidence of the
      population was 3.34%, much higher in children (3.69%) than in adults (0.41%). The
      boys were more frequently afflicted than the girls (4.69% versus 1.92%). There
      were no differences in the infection rates between rural and urban children.
      Young children (aged 1-3 years) with diarrhea and children in closed collective
      bodies are infection risk groups. The detection rate of persons infected with
      Cryptosporidium was much greater by the formalin-ether precipitation technique
      than that by the routine smear test. The correlation coefficient as to the
      infection rates detected by the routine smear tests was 1.75.

PMID- 9036290
TI  - [Nosocomial infections in Germany. Microbiological diagnosis, preventive
      antibiotics and antibiotic therapy].
AB  - BACKGROUND: The NIDEP-study (Nosocomial Infections in Germany-Prevalence and
      Prevention) is the first large multicenter survey to examine the prevalence of
      nosocomial infections (NI) in Germany. This part of the NIDEP-study describes the
      frequency and quality of the microbiological diagnosis, antimicrobial
      chemoprophylaxis and therapy in representative German hospitals. PATIENTS AND
      METHOD: Prevalence of nosocomial infections in 14 966 patients of 72 randomly
      selected representative German hospitals was determined. Frequency, nature and
      results of the microbiological diagnosis, antimicrobial chemoprophylaxis and
      therapy were recorded simultaneously. RESULTS: The total prevalence rate of
      nosocomial infections was 3.5%. The most common infections were urinary tract
      infections (42.1%), lower respiratory tract infections (20.6%), postoperative
      wound infections (15.8%), and septicemia (8.3%). Microbiological evaluation was
      done in 56.5% of the patients with infections. Only five of the 49 hospitals with
      less than 400 beds and only nine of the 23 hospitals with more than 400 beds had
      their own microbiological department. Antimicrobial chemotherapy was administered
      in 17.7% of the patients. In 35.1% of the patients who were treated with
      antibiotics, no clinical diagnosis of infection was made, criteria for nosocomial
      infections were not fulfilled or microbiological evaluation was not established.
      Antimicrobial chemoprophylaxis was done in one third of the patients. Prophylaxis
      was missed in 20.6% of patients with colorectal operations, 60.1% of
      appendectomies, 48% of vaginal hysterectomies, and 35.5% of total hip
      replacements. On the other hand antimicrobial chemoprophylaxis was frequently
      administered in clean procedures without increased risk of postoperative wound
      infections. CONCLUSION: Insufficient microbiological evaluation, inadequate
      perioperative antimicrobial chemoprophylaxis and administration of chemotherapy
      without documented infection were detected in representative German hospitals.

PMID- 9036291
TI  - [Coronary risk factors in chronic hemodialysis patients].
AB  - BACKGROUND: In contrast to persons with normal renal function, coronary risk
      factors or indicators until yet could not clearly be defined in renal
      insufficiency. PATIENTS AND METHODS: 30 patients under chronic hemodialysis
      therapy were investigated; 15 patients with severe coronary artery disease and 15
      patients with normal coronary angiogram were compared. Numerous factors of the
      manner of living (diet, smoking behaviour etc.) were registered and glucose and
      lipid metabolism, hemostatic and fibrinolytic system as well as blood pressure
      level were investigated. RESULTS: Besides higher HDL-cholesterol and tissue
      plasminogen activator (TPA) levels in patients without coronary heart disease, no
      significant difference could be found between both groups. The higher HDL levels
      were mainly due to the higher percentage of women in the coronary healthy group.
      There was no evidence of insulin resistance as a major pathogenic factor in the
      group with coronary heart disease. The blood pressure levels were not
      significantly different in both groups. CONCLUSION: Our quantitative examination
      of accepted or suspected coronary risk factors revealed no entity which turned
      out to be a reliable risk indicator for practical purposes.

PMID- 9036292
TI  - [Severe complications in diagnostic laparoscopy. 9 years experience in 747
      examinations].
AB  - BACKGROUND: Despite the introduction of non-invasive imaging procedures,
      diagnostic laparoscopy is still indicated in suspected liver cirrhoses, cancer
      staging and ascites or fever of unknown origin. Although the use of laparoscopy
      decreased over the last decade, some centers still have much experience and their
      complication rates are of special interest. PATIENTS AND METHODS: The
      complication rate of 747 patients undergoing a diagnostic laparoscopy in our
      clinic during the last 9 years is listed retrospectively, and the respective
      therapy is examined. RESULTS: Severe complications were found in 11 cases (1.5%):
      6 bleeding complications, 2 bowel perforations and 3 other complications. Five of
      these 11 patients had to be operated on (45%). One patient with metastatic
      gastric cancer died of a multiple organic failure following a lararoscopic tumor
      biopsy (0.13%). CONCLUSION: The diagnostic laparoscopy is of significant value
      and has still a low complication-rate in centers with special experience.

PMID- 9036293
TI  - [Therapy with antibiotics in renal failure].

PMID- 9036294
TI  - [Risk of secondary neoplasia after treatment of malignant germ cell tumors of the
      testis].

PMID- 9036295
TI  - [Percutaneous transluminal coronary angioplasty. Acute results and long-term
      follow-up].

PMID- 9036296
TI  - [Chronic constipation--diagnosis and therapy].

PMID- 9036297
TI  - [Breast carcinoma caused by constrictive clothing].

PMID- 9036298
TI  - [Social visit as an instrument for ambulatory hospital-based services for
      disabled patients].

PMID- 9036299
TI  - [Successful thrombolytic therapy in massive pulmonary embolism and right atrial
      thrombus--presentation of 2 case reports].

PMID- 9036300
TI  - [Percutaneous ethanol injection therapy of hepatocellular carcinoma].

PMID- 9036301
TI  - [Abciximab (c7E3)--a new monoclonal antibody--from the pharmaco-economic
      viewpoint. Initial reports from the literature].

PMID- 9036302
TI  - Let's go surfing! A physician guide to the Internet.

PMID- 9036303
TI  - mma.unveils.World.Wide.Web.home.page.

PMID- 9036304
TI  - Guidelines for prevention of nosocomial pneumonia. Centers for Disease Control
      and Prevention.
AB  - This document updates and replaces CDC's previously published "Guideline for
      Prevention of Nosocomial Pneumonia" (Infect Control 1982;3:327-33, Respir Care
      1983;28:221-32, and Am J Infect Control 1983;11:230-44). This revised guideline
      is designed to reduce the incidence of nosocomial pneumonia and is intended for
      use by personnel who are responsible for surveillance and control of infections
      in acute-care hospitals; the information may not be applicable in long-term-care
      facilities because of the unique characteristics of such settings. This revised
      guideline addresses common problems encountered by infection-control
      practitioners regarding the prevention and control of nosocomial pneumonia in
      U.S. hospitals. Sections on the prevention of bacterial pneumonia in mechanically
      ventilated and/or critically ill patients, care of respiratory-therapy devices,
      prevention of cross-contamination, and prevention of viral lower respiratory
      tract infections (e.g., respiratory syncytial virus [RSV] and influenza
      infections) have been expanded and updated. New sections on Legionnaires disease
      and pneumonia caused by Aspergillus sp. have been included. Lower respiratory
      tract infection caused by Mycobacterium tuberculosis is not addressed in this
      document. Part I, "An Overview of the Prevention of Nosocomial Pneumonia, 1994,
      provides the background information for the consensus recommendations of the
      Hospital Infection Control Practices Advisory Committee (HICPAC) in Part II,
      Recommendations for Prevention of Nosocomial Pneumonia." Pneumonia is the second
      most common nosocomial infection in the United States and is associated with
      substantial morbidity and mortality. Most patients who have nosocomial pneumonia
      are infants, young children, and persons > 65 years of age; persons who have
      severe underlying disease, immunosuppression, depressed sensorium, and/or
      cardiopulmonary disease and persons who have had thoracoabdominal surgery.
      Although patients receiving mechanically assisted ventilation do not represent a
      major proportion of patients who have nosocomial pneumonia, they are at highest
      risk for acquiring the infection. Most bacterial nosocomial pneumonias occur by
      aspiration of bacteria colonizing the oropharynx or upper gastrointestinal tract
      of the patient. Because intubation and mechanical ventilation alter first-line
      patient defenses, they greatly increase the risk for nosocomial bacterial
      pneumonia. Pneumonias caused by Legionella sp., Aspergillus sp., and influenza
      virus are often caused by inhalation of contaminated aerosols. RSV infection
      usually occurs after viral inoculation of the conjunctivae or nasal mucosa by
      contaminated hands. Traditional preventive measures for nosocomial pneumonia
      include decreasing aspiration by the patient, preventing cross-contamination or
      colonization via hands of personnel, appropriate disinfection or sterilization of
      respiratory-therapy devices, use of available vaccines to protect against
      particular infections, and education of hospital staff and patients. New measures
      being investigated involve reducing oropharyngeal and gastric colonization by
      pathogenic microorganisms.

PMID- 9036305
TI  - Compendium of animal rabies control, 1997. National Association of State Public
      Health Veterinarians, Inc.
AB  - This compendium provides information on rabies control to veterinarians, public
      health officials, and others concerned with rabies control. These recommendations
      serve as the basis for animal rabies-control programs throughout the United
      States and facilitate standardization of procedures among jurisdictions, thereby
      contributing to an effective national rabies-control program. This document is
      reviewed annually and revised as necessary. Recommendations for immunization
      procedures are contained in Part I; all animal rabies vaccines licensed by the
      United States Department of Agriculture (USDA) and marketed in the United States
      are listed in Part II; Part III details the principles of rabies control.

PMID- 9036306
TI  - The effect of digoxin on mortality and morbidity in patients with heart failure.
AB  - BACKGROUND: The role of cardiac glycosides in treating patients with chronic
      heart failure and normal sinus rhythm remains controversial. We studied the
      effect of digoxin on mortality and hospitalization in a randomized, double-blind
      clinical trial. METHODS: In the main trial, patients with a left ventricular
      ejection fraction of 0.45 or less were randomly assigned to digoxin (3397
      patients) or placebo (3403 patients) in addition to diuretics and angiotensin
      converting-enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average
      follow-up, 37 months). In an ancillary trial of patients with ejection fractions
      greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to
      placebo. RESULTS: In the main trial, mortality was unaffected. There were 1181
      deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo
      (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence
      interval, 0.91 to 1.07; P=0.80). In the digoxin group, there was a trend toward a
      decrease in the risk of death attributed to worsening heart failure (risk ratio,
      0.88; 95 percent confidence interval, 0.77 to 1.01; P=0.06). There were 6 percent
      fewer hospitalizations overall in that group than in the placebo group, and fewer
      patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7
      percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79;
      P<0.001). In the ancillary trial, the findings regarding the primary combined
      outcome of death or hospitalization due to worsening heart failure were
      consistent with the results of the main trial. CONCLUSIONS: Digoxin did not
      reduce overall mortality, but it reduced the rate of hospitalization both overall
      and for worsening heart failure. These findings define more precisely the role of
      digoxin in the management of chronic heart failure.

PMID- 9036307
TI  - Dietary trends in the United States.

PMID- 9036308
TI  - Dietary trends in the United States.

PMID- 9036309
TI  - Dietary trends in the United States.

PMID- 9036310
TI  - Enoxaparin as prophylaxis against thromboembolism after total hip replacement.

PMID- 9036311
TI  - Enoxaparin as prophylaxis against thromboembolism after total hip replacement.

PMID- 9036312
TI  - Prophylaxis against venous thromboembolism after major trauma.

PMID- 9036313
TI  - Association between prior cytomegalovirus infection and the risk of restenosis
      after coronary atherectomy.

PMID- 9036314
TI  - Association between prior cytomegalovirus infection and the risk of restenosis
      after coronary atherectomy.

PMID- 9036315
TI  - Heparin-induced skin necrosis.

PMID- 9036316
TI  - Heparin-induced skin necrosis.

PMID- 9036317
TI  - Heparin-induced skin necrosis.

PMID- 9036318
TI  - Heparin-induced skin necrosis.

PMID- 9036319
TI  - Heroin inhalation and progressive spongiform leukoencephalopathy.

PMID- 9036321
TI  - Trial of labor compared with an elective second cesarean section.

PMID- 9036320
TI  - Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic
      respiratory failure.
AB  - BACKGROUND: Neonates with pulmonary hypertension have been treated with inhaled
      nitric oxide because of studies suggesting that it is a selective pulmonary
      vasodilator. We conducted a randomized, multicenter, controlled trial to
      determine whether inhaled nitric oxide would reduce mortality or the initiation
      of extracorporeal membrane oxygenation in infants with hypoxic respiratory
      failure. METHODS: Infants born after a gestation of > or =34 weeks who were 14
      days old or less, had no structural heart disease, and required assisted
      ventilation and whose oxygenation index was 25 or higher on two measurements were
      eligible for the study. The infants were randomly assigned to receive nitric
      oxide at a concentration of 20 ppm or 100 percent oxygen (as a control). Infants
      whose partial pressure of arterial oxygen (PaO2) increased by 20 mm Hg or less
      after 30 minutes were studied for a response to 80-ppm nitric oxide or control
      gas. RESULTS: The 121 infants in the control group and the 114 in the nitric
      oxide group had similar base-line clinical characteristics. Sixty-four percent of
      the control group and 46 percent of the nitric oxide group died within 120 days
      or were treated with extracorporeal membrane oxygenation (P=0.006). Seventeen
      percent of the control group and 14 percent of the nitric oxide group died (P not
      significant), but significantly fewer in the nitric oxide group received
      extracorporeal membrane oxygenation (39 percent vs. 54 percent, P=0.014). The
      nitric oxide group had significantly greater improvement in PaO2 (increase,
      58.2+/-85.2 mm Hg, vs. 9.7+/-51.7 mm Hg in the controls; P<0.001) and in the
      oxygenation index (a decrease of 14.1+/-21.1, vs. an increase of 0.8+/-21.1 in
      the controls; P<0.001). The study gas was not discontinued in any infant because
      of toxicity. CONCLUSIONS: Nitric oxide therapy reduced the use of extracorporeal
      membrane oxygenation, but had no apparent effect on mortality in critically ill
      infants with hypoxic respiratory failure.

PMID- 9036322
TI  - Trial of labor compared with an elective second cesarean section.

PMID- 9036323
TI  - Trial of labor compared with an elective second cesarean section.

PMID- 9036324
TI  - Trial of labor compared with an elective second cesarean section.

PMID- 9036325
TI  - Perflubron in infants with severe respiratory distress syndrome.

PMID- 9036326
TI  - Intellectual function of children exposed to polychlorinated biphenyls in utero.

PMID- 9036327
TI  - Remission of progressive multifocal leukoencephalopathy following splenectomy and
      antiretroviral therapy in a patient with HIV infection.

PMID- 9036328
TI  - Advance medical planning.

PMID- 9036329
TI  - Advance medical planning.

PMID- 9036330
TI  - Costs of health care for the elderly.

PMID- 9036331
TI  - Costs of health care for the elderly.

PMID- 9036332
TI  - Costs of health care for the elderly.

PMID- 9036333
TI  - Costs of health care for the elderly.

PMID- 9036334
TI  - Stroke and pregnancy.

PMID- 9036335
TI  - Stroke and pregnancy.

PMID- 9036336
TI  - Health issues, the president and the 105th Congress.

PMID- 9036337
TI  - [Molecular pathogenesis of muscular diseases].
AB  - Recent advances in the field of molecular myology have provided significant
      insight into the pathological mechanisms underlying a variety of neuromuscular
      disorders. Genetic abnormalities can now be linked to primary and secondary
      pathophysiological changes in muscle fibres which compromise structural,
      metabolic, regulatory or contractile mechanisms. Ion channel myopathies such as
      paramyotonia congenita, hyper- and hypokalaemic periodic paralysis, myotonia
      congenita, episodic ataxia and malignant hyperthermia were established as linked
      to mutations in genes encoding the sodium channel, dihydropyridine receptor,
      chloride channel, potassium channel and the ryanodine receptor calcium release
      channel, respectively. Metabolic disorders affecting skeletal muscle were found
      to be due to deficiencies in a variety of enzymes. Identification of defects in
      components belonging to the gigantic dystrophin-glycoprotein complex led to the
      discovery of the molecular pathogenesis of Duchenne muscular dystrophy and
      related disorders. Based on these molecular findings, it is now feasible to
      design and evaluate new techniques such as gene and myoblast transfer therapy in
      order to replace defective components in diseased muscle fibres.

PMID- 9036338
TI  - [The Standard '(Threatened) Miscarriage of the Dutch Society of Family
      Physicians].

PMID- 9036339
TI  - [Tuberculosis as an unusual cause of oligoamenorrhea and infertility].
AB  - An 28-year-old Moroccan woman with primary infertility and OLIGO-amenorrhea was
      referred for hysteroscopic synechiolysis. When a diagnostic hysteroscopy was
      performed, a bizarre, irregular, 'cloudy' endometrium was seen. The diagnosis
      endometrial tuberculosis was confirmed by histological examination. Treatment
      with antituberculosis drug therapy resulted in a normal menstrual cycle. A normal
      endometrium and uterine cavity was seen at control hysteroscopy. Because of
      extensive irreparable tubal damage this patient will be offered IVF treatment.

PMID- 9036340
TI  - [Vancomycin-resistant enterococci . Work Group Hospital Infection Epidemiology].
AB  - Since 1995 patients with infections with vancomycin-resistant enterococci (VRE)
      have been reported in Rotterdam, the Netherlands. From prevalence studies in the
      Netherlands at the end of 1995 and the start of 1996, it appeared that 2% of the
      patients studied in and outside hospitals had VRE. Restrictive antibiotic
      prescription in human and veterinary medicine is indicated in order to postpone
      the problem.

PMID- 9036341
TI  - [The Standard '(Threatened) Miscarriage' of the Dutch Society of Family
      Physicians].

PMID- 9036342
TI  - [The Standard'(Threatened) Miscarriage' of the Dutch Society of Family
      Physicians].

PMID- 9036343
TI  - [The Standard '(Threatened) Miscarriage' of the Dutch Society of Family
      Physicians].

PMID- 9036344
TI  - [The Standard '(Threatened) Miscarriage of the Dutch Society of Family
      Physicians].

PMID- 9036345
TI  - [The Standard '(Threatened) Miscarriage' of the Dutch Society of Family
      Physicians].

PMID- 9036346
TI  - [Cesarean section or not in solutio placentae and signs of fetal distress?].

PMID- 9036347
TI  - [Cesarean section or not in solutio placentae and signs of fetal distress?].

PMID- 9036348
TI  - [Eye symptoms and latent diabetes].
AB  - Diabetes mellitus type II (non-insulin dependent diabetes mellitus) may run a
      prolonged subclinical course. In three patients, an indian man of 45, a man of 42
      and a woman of 78 years old, the first symptoms were eye disorders: vision loss,
      burning eyes with recurring chalazion, and (neurogenic) diplopia respectively.
      All three had elevated blood sugar levels and were treated accordingly.

PMID- 9036349
TI  - [Antibiotics in otitis media with effusion].
AB  - Otitis media with effusion usually resolves spontaneously. If not, long-term
      hearing impairment has to be prevented. The available literature indicates that
      antibiotic treatment has at most a short-term effect. Therefore it is not
      indicated for the treatment of otitis media with effusion.

PMID- 9036350
TI  - [Brain death criteria; guidelines by the Public Health Council].
AB  - The Committee on brain death criteria of the Health Council of the Netherlands
      has formulated guidelines for diagnosing brain death according to prevailing
      medical opinion. The guidelines are based on the relevant scientific literature
      and consultation of the professional groups involved and take into consideration
      that various views on death, or brain death, are existent in the community. The
      Committee has attempted to phrase the guidelines in clear and specific terms, in
      order to minimize interpretational differences. It endorses the most stringent
      definition of brain death, as given in the Organ Donation Act, the so-called
      'whole brain death' concept. It must be established that the potential donor has
      irreparable and complete loss of brain and brain stem function. Three diagnostic
      phases are needed. In one of these an isoelectric electroencephalogram is
      required. This does not preclude that certain neurons in certain areas may still
      be active, but these phenomena are no indication of higher brain function or its
      intermediary or supportive functions. If electroencephalography cannot be
      performed, or if the apnoea test is not possible, cerebral arterial angiography
      is required. In children, the investigations must be repeated. A written codicil
      by the donor will be respected, but it is unlikely that organs or tissues are
      removed against the will of the family.

PMID- 9036351
TI  - [Mycobacterium avium infection in HIV-infected patients: epidemiology, diagnosis,
      prevention and treatment].
AB  - The prevalence of infection with Mycobacterium avium complex (MAC) has increased
      since the outbreak of the HIV pandemic. This complex comprises two organisms: M.
      avium (mostly) and M. intracellulare (rarely). The source of MAC infection is not
      known. The principal risk factors for disseminated MAC infection in a patient
      with HIV infection are a low CD4 count and a previous opportunistic infection.
      The symptoms of disseminated MAC infection resemble those of HIV wasting; a
      positive culture of normally sterile tissue confirms a MAC infection. There is
      reserve with regard to routine prophylaxis in HIV-infected persons because of the
      possible development of resistance, interaction with other drugs used in AIDS,
      toxicity and possible absorption disorders which might cause prophylaxis to fail.
      For the treatment of disseminated MAC infection, a combination of at least two
      medicaments (macrolides and ethambutol) is recommended.

PMID- 9036352
TI  - [Angiotensin-converting enzyme inhibitors following a myocardial infarct:
      clinical abd echographic indications].
AB  - -Angiotensin converting enzyme (ACE) inhibitors can limit mortality and the
      occurrence of cardiac failure after myocardial infarction because they interfere
      with the ventricular remodelling process. ACE inhibitors also have anti
      arrhythmic and possibly anti-ischaemic potency and therefore a primary
      cardioprotective effect. It is not advised to treat all patients with a
      myocardial infarction with an ACE inhibitor, but patients with a large anterior
      wall infarct, with heart failure or who had a previous infarct should be treated.
      After three months, the remodelling process can be reevaluated. The ACE inhibitor
      can be discontinued if the left ventricular function has strongly improved. There
      is no preference for a particular ACE inhibitor.

PMID- 9036353
TI  - [Echographic recognition of tuberculous peritonitis].
AB  - OBJECTIVE: To assess the role of ultrasonography (US) and US-guided puncture in
      the diagnostic procedure of tuberculous peritonitis. DESIGN: Retrospective study.
      SETTING: An inner-city hospital: Westeinde Ziekenhuis, The Hague, the
      Netherlands. METHODS: Of 12 patients with bacteriologically confirmed tuberculous
      peritonitis diagnosed between 1987 and 1995, the results of ultrasonography and
      the bacteriological and cytological results of US-guided puncture were studied.
      RESULTS: The ultrasonographic appearance of wet tuberculous peritonitis was
      recognized by the radiologist in all 11 cases. There was loculated ascites with
      fine septations as well as thickening of peritoneum, mesentery and omentum.
      Ultrasonography was of no merit in the one case of peritonitis sicca in this
      study. US-guided puncture of ascites and omentum yielded a bacteriological
      diagnosis in eight patients, six of whom had a positive Ziehl-Neelsen or auramine
      test. In two other patients cytological examination showed a granulomatous
      inflammation. On average, the ultrasonographic diagnosis of wet tuberculous
      peritonitis was suggested 3 days after admission and bacteriologically confirmed
      10 days later. Eleven of the 12 patients were immigrants from countries where
      tuberculosis is endemic. The mean duration of residency in the Netherlands was 7
      years. CONCLUSION: Ultrasonography is valuable in the diagnostic procedure of
      tuberculous peritonitis in that it considerably reduces diagnostic delay and
      unnecessary surgical procedures are avoided.

PMID- 9036354
TI  - [Cost-effectiveness of influenza vaccination The Netherlands].
AB  - OBJECTIVE: To determine the cost-effectiveness of influenza vaccination of all
      people aged 65 or over in the Netherlands. DESIGN: Model calculations. SETTING:
      National Institute of Public Health and Environment, Bilthoven, the Netherlands.
      METHOD: The cost-effectiveness of vaccination strategies was calculated using a
      mathematical model, with which the epidemiological effects in terms of morbidity
      and mortality as well as the direct costs of care of an influenza epidemic can be
      determined. The cost-effectiveness of non-intervention, of the current
      vaccination scenario for risk groups, and of an alternative scenario involving
      vaccination of all persons aged 65 or over and of all younger persons in risk
      groups, was calculated. RESULTS: Influenza-related care (the number of GP
      contacts and hospital days) and related costs decreased more with the alternative
      than with the current risk group scenario. Although the costs of care decreased
      when more people were vaccinated, the cost of vaccination increased more so that
      total net costs rose (55 million guilders versus 24 million). In the alternative
      scenario yearly 1115 life years more were won than with the current practice.
      CONCLUSION: Vaccinating all risk groups and all persons aged 65 or more has a
      favourable cost-effect ratio in comparison with other preventive intervention
      programmes.

PMID- 9036355
TI  - [Differential diagnostic considerations on retrobulbar neuritis].
AB  - Retrobulbar neuritis is a frequent diagnosis in patients (age groups 20-40
      years), who complain about acute monocular loss of vision, accompanied by painful
      eye movements. The clinical course with recovery over about six weeks and the
      possibility of additional neurological dysfunction in the following years confirm
      the diagnosis of primarily demyelinating disease. Beside the typical retrobulbar
      neuritis, there is a group of vascular optic nerve disorders as well as Leber's
      optic neuropathy that need to be differentiated from primary demyelinating
      retrobulbar neuritis. Compressive optic neuropathies, unilateral chiasm disorders
      and infiltrative optic neuropathies will not be considered in this paper, because
      of their subacute presentation.

PMID- 9036356
TI  - [Headache and the cervical spine. A critical review].
AB  - Headache in association with the cervical spine is often misdiagnosed and treated
      inadequately due to confusing and varying terminology. Primary headaches such as
      tension-type headache and migraine are incorrectly categorized as "cervicogenic"
      merely because of their occipital localization. Cervicogenic headache described
      by Sjastaad presents as a unilateral headache of fluctuating intensity increased
      by movement of the head and typically radiating from occipital to frontal
      regions. Definition, pathophysiology, differential diagnosis and therapy of
      cervicogenic headache shall be demonstrated. Ipsilateral blockades of the C2/ C3
      root and/or the major occipital nerve allow a differentiation between migraine
      and other primary headache syndromes. Neither pharmacological nor surgical or
      chiropractic procedures lead to an improvement or remission of cervicogenic
      headache. Pain of various anatomical regions possibly join into a common
      anatomical pathway then presenting as cervicogenic headache, which should
      therefore be understood as a homogeneous but also unspecific pattern of reaction.

PMID- 9036357
TI  - [Genetics of migraine].
AB  - Several historical reports focusing on the heredity of migraine, as well as
      recent studies on its epidemiology and molecular biology, have revealed evidence
      for a decisive role of genetic factors in the aetiopathogenesis of familial
      migraine. Indeed, family studies, segregation analyses and twin studies have
      shown that genetic factors play an important role in disposition towards migraine
      but could not explain the entire aetiopathogenesis. The influence of extragenetic
      factors, however, remains mostly unknown. Recent linkage analyses have provided
      evidence for genetic heterogeneity. A locus for Familial Hemiplegic Migraine
      (FHM), the only known type of migraine that follows autosomaldominant
      transmission, has been linked to chromosome 19p13 but genetic heterogeneity has
      also been shown, i.e., different types of migraine could be excluded from this
      locus. Further investigations should concentrate on identifying the FHM gene on
      chromosome 19p13, on linkage analyses with markers for different susceptibility
      genes, and on genomic analyses of highly informative pedigrees. This would lead
      to further clues to the pathogenesis underlying migraine and, thus, to
      therapeutic developments.

PMID- 9036358
TI  - [Exteroceptive suppression of activity of the temporal muscle. Principles and
      applications].
AB  - The exteroceptive suppression period (ES) of the temporalis muscle activity is a
      trigemino-trigeminal brain stem reflex. It will be elicited most when stimulating
      trigeminal sensory afferents by painful stimuli and typically leads to a biphasic
      interruption of voluntary muscle activity. The first phase of decreased voluntary
      activity is called the early exteroceptive suppression period (ES1), the second,
      the late exteroceptive suppression period (ES2). Between these two suppression
      periods a phase of increased muscle activity, the so-called facilitation period
      (FP), can be seen. This phenomenon can be modulated by different stimulating
      parameters and usually, in healthy subjects, this normal pattern of the
      exteroceptive suppression can be elicited regularly. The reflex answer may occur
      at low non-painful stimulus intensities; typically, however, it appears to be
      most pronounced with high-intensity stimuli. Because of the obvious relationship
      between stimulus intensity, pain perception and reflex, the reflex is regarded as
      an antinociceptive reaction. The absence of an inhibition of motor activity can
      be visualized, for example, in hemimasticatory spasm or dystonic disorders.
      However, above all the ES nowadays attracts most attention as a tool to analyse
      different pain syndromes. One main advantage of this method in man is the ability
      to evaluate certain antinociceptive brain stem mechanisms functionally by means
      of a simple noninvasive technique. A large number of results have been obtained
      showing that chronic pain syndromes such as chronic tension-type headache and
      migraine cause changes within the normal ES recording pattern. Furthermore, some
      substances used in pain therapy, such as serotonin agonists or antagonists,
      acetylsalicylic acid or naloxone, may also alter the general appearance of the
      ES. This review will summarize different parameters that influence the ES reflex
      answer. Furthermore, the diagnostic value of changes in the ES for
      pathophysiological processes regarding pain perception and processing in certain
      pain syndromes will be discussed.

PMID- 9036359
TI  - [Differential therapy of cerebral arteriovenous malformations. An analysis with
      reference to personal microsurgery experiences].
AB  - A total of 126 patients (63 female, 63 male) underwent microsurgical removal of
      their cerebral arteriovenous malformations (AVMs) by the same surgeon. The mean
      age at surgery was 34.7 (6-72) years. The symptoms were intracerebral hemorrhage
      (37.3%), seizure disorder (34.9%) or focal neurological deficits and minor
      symptoms. According to the Spetzler/Martin scale, 20.6% of the AVMs were grade I,
      28.6% grade II, 32.5% grade III, 14.3% grade IV and 4% grade V. In all, 78 AVMs
      (61.9%) were located in functionally important brain regions. The series was
      split into three different groups: small AVMs under 3 cm in diameter (n =
      62/49.2%), medium-sized AVMs (n = 58/46%) and large AVMs (n = 6/4.8%). Seventeen
      patients had preoperative embolization of their AVM. All patients had
      postoperative angiographic control and 3- and 6-month follow-up. One patient died
      (0.8%), and another one (0.8%), in whom the AVM was incompletely resected,
      suffered a secondary hemorrhage. Seventeen (27.4%) of the patients with small
      AVMs developed transient neurological worsening post-operatively, which remained
      permanently significant in 3.2%. The respective numbers for the patients with
      medium-sized AVMs were 48.3% and 10.3% and for the large AVMs 83.3% and 33.3%.
      The results of microsurgical removal of cerebral AVMs can still be considered
      superior to the results of stereotactic radiosurgical treatment available from
      the literature-even for small AVMs. This is due to immediate exclusion of the AVM
      under direct local control of the angioarchitecture and thereby a reduced risk of
      secondary hemorrhaging and a decreasing morbidity rate with increasing time after
      the operation. Radiosurgical treatment requires a 2-year latency period for
      obliteration and carries a mortality rate of up to 12.5% and a rate of unexpected
      side effects of up to 20%. This treatment should be reserved for small, deep,
      surgically inaccessible AVMs or used as part of a multimodality treatment regimen
      consisting of partial embolization, partial excision and consecutive radiation of
      the residual nidus in initially very large AVMs. Embolization therapy-such as
      radiosurgery-carries a significant risk of morbidity (8%) and a mortality rate of
      up to 6%. It should only be considered for AVMs that are expected to be fully
      obliterated afterwards, or for primary inoperable AVMs that are to be changed
      into operable ones by embolization. Size reduction of otherwise operable AVMs
      does not justify the additional risk of embolization. Close collaboration of the
      specialties involved is desirable.

PMID- 9036360
TI  - [Familial nocturnal frontal lobe epilepsy. Clinical aspects and genetics].
AB  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a disease entity
      that has only recently been discovered. Its clinical variability and the
      frequently missed EEG features are probably some of the reasons why this disease
      is often overlooked or misdiagnosed. In a large Australian pedigree, a link was
      found between ADNFLE and polymorphic markers on chromosome 22q13.2-q13.3.
      Mutation analysis identified a mis-sense mutation in the gene coding for the
      alpha 4 subunit of the neuronal nicotinic acetylcholine receptor. The mutation
      was found in all affected family members. Thus, for the first time a likely
      relationship between an idiopathic epilepsy and a specific gene has been found.
      Additional studies will be needed to clarify the underlying pathologic mechanism.
      Furthermore, the hypothesis that other members of this multigene family are
      involved in epileptic diseases appears attractive.

PMID- 9036361
TI  - [Acute reversible encephalopathy with brain edema and serial seizures in
      pseudohypoparathyroidism].
AB  - A 16 year old patient with the typical clinical signs of Albright's hereditary
      dystrophia developed series of epileptic seizures with loss of consciousness,
      tonic muscle contractions and bite of the tongue. After termination of the
      seizures there was coma without focal neurological signs. CT scan revealed
      diffuse brain edema. Electroencephalographic studies showed generalized slowing.
      In laboratory tests the only abnormalities were marked hypocalcemia (1.15 mmol/l)
      and hyperphosphatemia. Blood parathyroid hormone (PTH) was elevated. PTH-Test
      confirmed the diagnosis of pseudohypoparathyroidism. The patient was treated with
      calcium and 1,25-dihydroxy-cholecalciferol. After few days the severe
      encephalopathy, CT and electroencephalographic changes were completely
      reversible. Hereditary disturbances of the parathyroid hormone metabolism are
      rare diseases. Hypocalcemia must be included into the differential diagnosis of
      seizures and brain edema to avoid invasive diagnostic and irrational treatment.

PMID- 9036362
TI  - [Involvement of the central nervous system in hemolytic uremic
      syndrome/thrombotic thrombocytopenic purpura].
AB  - Cerebral involvement is typical for thrombotic microangiopathies like haemolytic
      uremic syndrome (HUS) and thrombotic-thrombopenic purpura (Moschcowitz disease or
      TTP). Symptoms are irritation, restless behaviour, disorientation, disturbance of
      consciousness, seizures, and focal neurological deficits. The lack of typical
      imaging changes or pathological observations may explain the unknown
      pathophysiological cascade leading to the neurological symptoms. We describe the
      development of HUS/ TTP in a 52-year-old woman after acute pneumonia caused by
      Diplococcus pneumoniae. The patient showed an increasing psycho-organic syndrome
      with disorientation, followed by severe loss of consciousness and coma.
      Initially, computed tomography showed slight diffuse brain oedema, which was not
      found in later follow-up images. Magnetic resonance imaging was normal. The TCD
      examination revealed general velocity increases and vasospasms (especially MCA,
      ACA and PCA bilateral and BA). The reduction in blood flow velocities in the
      basal arteries was accompanied by a marked clinical improvement. The development
      of vasospasms may be an explanation for the neurological deficits in HUS/TTP. The
      origin of the vasospasms may be found in disturbed prostacyclin production,
      increased serotonin or platelet factor IV release, and leucocyte activation with
      consecutive endothelial damage.

PMID- 9036363
TI  - [Sensory Jacksonian seizures as initial manifestation of sarcoidosis].
AB  - A 46-year old patient is reported presenting with somatosensory focal seizures of
      either arm as the only manifestation of an otherwise clinically inapparent
      sarcoidosis. MRI showed signs of a granulomatous leptomeningeal affection.
      Histological examination of a meningeal biopsy proved the diagnosis of
      sarcoidosis by demonstrating noncaseating granulomas. There was no other clinical
      manifestation of sarcoidosis. Chest X-ray was normal and the serum level of
      angiotensin-converting-enzyme was only slightly elevated. The CD4/CD8 ratio in
      the bronchoalveolar lavage cell population, however, was clearly abnormal,
      supporting the role of this diagnostic tool in the diagnosis of sarcoidosis.

PMID- 9036364
TI  - [Low molecular weight heparin: immediate therapy of stroke? A discussion of the
      study by Kay et al.: Low molecular weight heparin for treatment of acute ischemic
      stroke].

PMID- 9036365
TI  - [Demography and effects of chronic renal insufficiency in Ile-de-France].
AB  - In order to assess the incidence of chronic renal failure (CRF) and the
      demographic characteristics of affected patients, a prospective, multicenter
      epidemiologic study was conducted with the cooperation of all nephrology and
      dialysis units in the Ile-de-France district, the total population of which is
      10660000 inhabitants (source: national census, march 1990). Included were
      patients with a plasma creatinine (Pcr) concentration > or = 200 mumol/l referred
      during the one-year period from July 1, 1991 until June 30, 1992. The overall
      response rate was 98.5%. A total of 2775 adult patients were recorded, including
      1780 males (64%) with a mean (+/- SD) age of 58.1 +/- 16.3 years and a mean Pcr
      of 447 +/- 214 mumol/l, and 995 females (36%) with a mean age of 59.2 +/- 16.4
      years and a mean Pcr of 425 +/- 185 mumol/l. Age of patients was < 40 in 16%, 40
      59 in 31%, 60-74 in 34% and > or = 75 years in 19%. Pcr was 200-399 mumol/l in
      54%, 400-599 mumol/l in 25%, 600-799 mumol/l in 12% and > or = 800 mumol/l in 9%.
      The overall incidence of CRF was 260/million population/year, twice higher in
      males than in females (348 vs 179/10(6)/year, p < 0.001). Incidence of CRF
      dramatically rose with age in both genders, with figures as high as 1124 and
      356/10(6)/year respectively in male and female patients aged > or = 75 years, vs
      288 and 151/10(6)/year in patients aged < 40 years. A sequential evaluation was
      performed in a representative sample of 251 patients with initial Pcr > or = 300
      mumol/l. End-stage renal failure (ESRF) was reached within one year in 99% of
      patients with PCr > 600, 49% with Pcr 500-599, 24% with PCr 400-499 and 11% with
      PCr 300-399 mumol/l. Based on these figures, the predicted incidence of ESRF
      within one year of referral was 864 out of the 2775 patients, an estimated annual
      incidence of 81 patients per million population. In conclusion, this prospective
      study affords the first direct information on the incidence of chronic renal
      failure and the demographic characteristics of patients with CRF in the Ile-de
      France district. Due to the design of the study conducted only in nephrology
      units, the estimated figure of 81 new patients per million population per year
      reaching ESRF is a minimal evaluation. In view of the relentless aging of
      population in France, an incidence of at least 100 ESRF patients per million
      population per year is to be expected in the next future.

PMID- 9036366
TI  - [Monoclonal antibodies and transplantation].
AB  - Several monoclonal antibodies have been evaluated in allograft transplantation,
      these past years, without being able, to date, to replace polyclonal antibodies.
      They are classified in four families, each having an individual interest:
      antibody directed against the CD3/T receptor complex; anti-interleukine II
      receptor antibodies, specifically blocking activated T lymphocytes; antibodies
      against adhesion molecules, mainly LFA1 and ICAM1, that, by preventing the
      reperfusion injury syndrome, should have many clinical applications in the
      future; antibodies against co-receptor molecules, such as CD4, inducing
      indefinite allograft tolerance in models of transplantation in rodents, that
      could be reproducible in human.

PMID- 9036367
TI  - [Value of cyclosporine in the treatment of the recurrence of nephrosis after
      renal transplantation].
AB  - From May 1992 to December 1994, 14 children with end stage renal failure
      secondary to steroid-resistant idiopathic nephrotic syndrome received a cadaver
      kidney graft. Immediate recurrence of the nephrotic syndrome occurred in four
      patients. In the four patients, a complete remission was observed shortly after
      the start of intravenous cyclosporin; two children received in addition
      methylprednisolone pulses for secondary rejection. Two children were still
      protein-free 9 and 15 months after transplantation. In the third patient,
      proteinuria relapsed after 9 months of complete remission and persisted in spite
      of the reintroduction of intravenous cyclosporin. The fourth graft was lost at
      3.5 month from irreversible rejection. The creatinine clearance of the 3
      functioning grafts was respectively: 73, 76 and 92 ml/mn/1.73 m2 16, 10 and 15
      months after transplantation. Intravenous cyclosporin started shortly after the
      recurrence, maintaining blood levels between 200 and 300 ng/ml, may induce a
      remission in recurrent nephrotic syndrome after renal transplantation in
      childhood.

PMID- 9036369
TI  - [PRA-STAT test and anti-HLA antibody detection].

PMID- 9036368
TI  - [Femoral indwelling silicone catheter: experience of three hemodialysis centers].
AB  - The use of femoral vein for temporary access in hemodialysis patients is still
      considered as a slightly desirable route. However recent technical improvements
      have made this approach more reliable because the new femoral catheters can be
      left in place for a long time and used for ambulatory treatment. We describe the
      experience of three hemodialysis centres with temporary indwelling femoral
      catheter made of silicone (SSL 1220 M, Medcomp) in 55 patients: 3 patients with
      acute renal failure, 1 requiring plasmapheresis and 51 with chronic renal failure
      but no other available vascular access. Sixty four catheters were implanted and
      left in place for a mean of 41.5 +/- 30 days. Complications (mechanical,
      thrombotic and infectious) were infrequent and never life-threatening. These
      results suggest that the femoral route can be used reliably for temporary access,
      and provides advantages over subclavian and jugular routes in certain
      circumstances.

PMID- 9036370
TI  - [Commentary on the editorial by J. Touzet: "Will to die, palliative care and
      medical responsibility"].

PMID- 9036371
TI  - [History of glomerular sclerosis].

PMID- 9036372
TI  - Environmental risk perception, activism and world-mindedness among samples of
      British and U.S. college students.

PMID- 9036373
TI  - [Cell polarity, polar proteins and cytokinesis].

PMID- 9036374
TI  - [The role of chromatin complexes in regulation of gene expression during
      development].

PMID- 9036375
TI  - [MAP kinases and their role in regulation of protein level, subunit composition
      and degree of phosphorylation of transcription factor AP-1].

PMID- 9036376
TI  - [Molecular bases of cytoplasmic male sterility in higher plants].

PMID- 9036377
TI  - [The role of nuclear genome in regulation of mitochondrial function in
      Saccharomyces cerevisiae].

PMID- 9036378
TI  - [Plant respiratory chains].

PMID- 9036379
TI  - [Controlled biosynthesis of polyketide antibiotics].

PMID- 9036380
TI  - [Deficiency of arylsulfatase A activity as a basis of metachromatic
      leucodystrophy].

PMID- 9036381
TI  - [Phosphatidylinositol-specific phospholipase C isozymes and regulation of their
      activity].

PMID- 9036382
TI  - [Sphingomyelin and its metabolites as an intermediate in cellular signal
      transduction].

PMID- 9036383
TI  - [Child and adolescent welfare regulation in case of separation and divorce].

PMID- 9036384
TI  - [Parenthood and cooperation in legal custody determination].
AB  - Dealing with custody and visitation problems forensic psychology has to refer to
      the findings and construct-developments of the particular psychological fields.
      In a discoursive manner this is shown for the crucial concepts of parenthood and
      cooperation. An expanding number of new studies about parenting and parenthood,
      mostly in the domain of developmental psychology, is reviewed, status and
      validity of the scientific constructs and consequences for forensic-psychological
      affairs are discussed. Gains and desiderata are indicated. The bio-psycho-social
      character of parenting is emphasized as well as the integration of these elements
      in an interdisciplinary way. A review of the literature concerning cooperation is
      less productive. Cooperation is mainly discussed in the realm of conflict
      solution and operationalized by variants of the prisoners-dilemma-game. The
      essence of those approaches and the implications for separation or divorce and
      regulation of its effects are shown. Findings of psycho-biological studies are
      added as well as considerations to use them conditionally by analogy. Finally a
      guide or rather a schema for interviews in familypsychological examination is
      proposed.

PMID- 9036385
TI  - [Recommendations for terminating child custody--reasons and grounds in 30 expert
      decisions].
AB  - In a retrospective analysis 30 expert opinions on the right of visitation, which
      recommend the exclusion of this right for the non-custodial parent, are
      evaluated. These cases represent 23% of the expert opinions concerning the right
      of visitation that have been given by the department of Child and Adolescent
      Psychiatry of the University of Tubingen between 1991 and 1994. Focusing on the
      decisive argument for the expert to exclude the right of visitation, it became
      apparent that in 40% of the cases the will of the child was the determining
      factor, followed by sustained tension between the parents in 33% of the cases.
      Emotional neglect, (continuous) abuse and maltreatment (12%) as well as offences
      against the clause of good behaviour (Wohlverhaltensklausel) were of significant
      smaller influence on the decision. And although 61% of the children have been
      classified as psychological disturbed, only in 5% of the cases this diagnosis was
      of importance.

PMID- 9036386
TI  - [Dynamics of child suggestibility in accusations of sexual abuse in divorce
      proceedings].
AB  - A case of a mother confabulating an extended sexual abuse of her 13 and 15 year
      old children involving bizarre sadistic features is presented and discussed. The
      kinship to Munchhausen Syndrome by proxy, identity diffusion, Posttraumatic
      Stress Syndrome, folie a deux and other concepts is highlighted. It is suggested
      that sexual confabulations are generated within incestuous family structures as a
      means to stimulate and satisfy needs of personal closeness when losses and
      disruptive events have occurred. The disclosure or suspicion of sexual abuse may
      prove neither true nor false but may hint to an impending emotional breakdown of
      a parent and to ongoing subtle incestuous traumatisation of a child.

PMID- 9036387
TI  - [Legal family assessment in the case of alcoholic parents].
AB  - Legal testimony in families with alcohol abusing parents requires extensive
      psychological assessment concerning developmental risks and coping resources of
      the children, specific characteristics of abuse, abuse related behaviour and
      comorbidity of the alcohol abusing parent als well as morbidity of the non
      alcoholic parent. Children of alcoholics and their parents themselves need long
      term help beyond the process of divorce and legal activities which demands close
      cooperation between social institutions involved.

PMID- 9036388
TI  - Synthesis and analgesic properties of new 4-arylhydrazone 1-H pyrazole [3,4-b]
      pyridine derivatives.
AB  - Based on the principle of bioisosterism, a successful strategy in the planning of
      new drugs, we describe in this work the synthesis and the analgesic activity of
      the new functionalized arylcarbaldehyde 4-(1-phenyl-3-methylpyrazolo[3,4
      b]pyridine) hydrazone derivatives 5a-m. These derivatives (5a-m) were synthesized
      in ca. 45% overall yield, using 4-(1-phenyl-3-methylpyrazolo[3,4-b]pyridinyl)
      hydrazine 6, as key intermediate. by applying classical synthetic methods to
      construct the aryl-hydrazone unit at C-4 of the heterocyclic system. Compound 6
      was prepared from the corresponding 4-chloro-(N-phenyl-3-methylpyrazolo[3,4
      b]pyridine) derivative 7 in very high yield. The antinociceptive activity of
      these new compounds 5a was evaluated by a test of abdominal contortions induced
      by 0.6% acetic acid solution i.p. in albino mice. The compounds 5f, 5g, 5j and 5k
      were strongly active showing a good analgesic profile.

PMID- 9036389
TI  - [Sensitivity and selectivity enhancing parameters in the determination of
      substances in biological material in the pg range with HPLC and electrochemistry
      detection using a new xanthine derivative].
AB  - Quality aspects influencing the determination of a xanthine derivative in plasma
      by HPLC and coulometric detection are described. The experiences made within the
      scope of these experiments enable an adequate optimization of the method and a
      practical and time saving qualification of the status of sensitivity of the
      electrochemical working electrode.

PMID- 9036390
TI  - [Biotransformation in hen's eggs. Metabolic transformation of p-nitrophenol].
AB  - Not only phase I reactions but also phase II reactions can be detected using
      embryonated chicken eggs as an alternative method for biotransformation studies.
      Previously reported investigations which enabled the detection of the phase II
      products of 7-ethoxycoumarin in the allantois after enzymatic conjugate cleavage
      have since been supplemented by the development of a direct method. The
      glucuronidation and sulfation of p-nitrophenol were chosen as model reactions for
      this direct detection of conjugation reactions. The utility of the previously
      developed method for application to biotransformation investigations involving
      the detection of metabolites in the allantois in fertile chicken eggs has now
      been substantiated for the model substance p-nitrophenol. p-Nitrophenyl sulfate
      and p-nitrophenyl glucuronide were directly identified as phase II metabolites
      after incubation and work-up by HPLC analysis as well as comparison of their
      spectra with those of authentic substances. The conversion rates obtained are
      very high and well comparable with those of in vivo investigations in chickens.
      It would seem that the metabolism of hydrophilic substances can be advantageously
      studied in chicken eggs.

PMID- 9036391
TI  - [Binding of epirubicin to human plasma protein and erythrocytes: interaction with
      the cytoprotective amifostine].
AB  - The in vitro binding rate of epirubicin (EPR) to different plasma proteins,
      control serum, red blood cells and whole blood was investigated without and with
      the cytoprotective agent amifostine. The binding rate of EPR to plasma proteins
      fractions and red blood cells dependend on the concentration of the matrix
      components. EPR was bound more than 90% to human serum alpha-globulin (alpha
      HSG), to human serum albumine (HSA) and human serum beta-globuline (beta-HSG) at
      80 to 90%, in the case of human serum gamma-globulin (gamma-HSG) the binding rate
      amounted 75%. The binding rate of EPR to RBCs in whole blood samples reached 38%.
      Within the observed concentration range of proteins (1-40 micrograms/ml,
      depending on the protein concentration) AMI caused a reduction of the protein
      bound amount of EPR in the range from 2 to 19% of HSA, 4 to 20 in the case of
      beta-HSG, 2 to 32% in the case of alpha-HSG and 17 to 21% for gamma-HSG. In the
      whole blood samples the binding of EPR to proteins dropped from 45 to 32% and RBC
      partitioning from 38 to 32%. Two compounds with free thiol groups, cystein and
      glutathione, were compared with AMI in regard to lowering the binding rate of EPR
      to HSA: the effect was exactly in the same order of magnitude: -17% for AMI, 
      21.0% for cystein and -20.8% for glutahion (p < 0.002). For a negative control,
      cystin and phenylalanin were tested, too: both compounds showed no influence on
      the protein binding of EPR: 63.8% binding rate in the control group, 65.2% in the
      presence of cystin and 64.6% in the presence of phenylalanin (statistically not
      significant). The present results indicate, that binding of EPR to serum proteins
      is reduced in the presence of AMI by interaction of the thiol-group with the
      protein and that the thiophosphoric ester bond in the test solution must cleave
      rapidly.

PMID- 9036392
TI  - [The difficulties of women in psychiatry].

PMID- 9036393
TI  - [The career course of women and men psychiatrists].
AB  - Data from a survey distributed to all directors of psychiatric hospitals in
      Germany (n = 286) were used to examine sex differences in rank attainment among
      psychiatrists. Furthermore the directors were asked to assess differences between
      male and female psychiatrists concerning their professional activities. A total
      of 207 directors responded, 10 of them were female. In the rank of assistant
      doctors male psychiatrists predominated only at the university departments (61%).
      The position of a registrar was held mainly by male doctors in all types of
      hospitals: 78% at the university departments, 64% at psychiatric hospitals and
      56% at psychiatric departments at general hospitals. 43.9% of the responders
      assessed women less interested in a professional career than men, 46.5% thought
      that women are more interested in treatment than in research activities, 43.5%
      admitted that in case of female applicants their private situation (family,
      children) is more important for the decision to give a job than in case of male
      ones. 87% of the directors found that a higher number of women within their teams
      is very important for a good work climate.

PMID- 9036394
TI  - [Ecstasy, a new designer drug in the techno-scene].
AB  - Ecstasy is the term of MDMA, which is spread most of all in the techno scene.
      Wellknown for centuries as an agent of the nutmeg, MDMA was discovered as a drug
      during the last decades. Origin, physical and psychical effects and the results
      of chronicle abuse are described. Consume of XTC as a typical drug abuse of the
      techno scene represents a new challenge for the classical drug aid system. There
      are only few points of contact with the heroin scene.

PMID- 9036395
TI  - [Integration of new psychosocial facilities into the health care system:
      considerations on a social ecological evaluation concept exemplified by
      ambulatory crisis care].
AB  - With respect to the methodological problems concerning the outcome evaluation of
      crisis intervention centers the outlines of a social-ecological research approach
      are developed. It is suggested that this approach is more suitable to take into
      account the role of the network of mental health services. The data come from a
      research project which was designed to explain the historical and social aspects
      of the process of integration of a crisis intervention service. The results
      indicate that on the one hand the practice of the service strongly depends on
      what other services do and on the other hand influences them. The social
      integration of an institution into the network of other services is discussed as
      an alternative criterion of evaluation.

PMID- 9036396
TI  - [Pre- and postadmission treatment--possible applications for psychiatry].
AB  - German Health Legislation has recently issued regulations for cuts in health
      expenditure. One of the new proposed services is pre- and post in-patient
      treatment services. Hitherto their realization has mainly been seen in somatic
      disciplines, mainly surgery. The author shows that psychiatry will gain more
      efficiency and quality of psychiatric care through implementation of these
      services. The threefold spectrum of psychiatric treatment facilities (in-patient,
      out-patient, day-treatment) will thus be upgraded into a five-dimensional
      treatment. It is shown, that most of these new treatment facilities have been
      lain dormant in day-to-day psychiatric practice, the new legislation helps the
      psychiatric profession to set them in motion. Examples for possible use are
      given.

PMID- 9036397
TI  - [Family meetings].

PMID- 9036398
TI  - [The social status of schizophrenic patients during the course of 8 years
      catamnesis and significance of relatives for psychosocial integration].
AB  - The development of the social situation of 69 DMS-III schizophrenic out-patients
      is described in an 8 years follow-up. Originally all patients had lived with
      their relatives. Patients who lived with spouses or alone (each 20%) had quite a
      good outcome and a fair social integration. After 8 years 40% still lived with
      parents. They needed much support from them for their course of illness was
      moderate. 20% lived in sheltered accommodations and had a poor integration. For
      all the relatives were the most important reliable persons in social networks
      which decreased during the course of illness.

PMID- 9036399
TI  - [Effect of partially open department on unit atmosphere].
AB  - Ward atmosphere was assessed with the help of the Ward Atmosphere Scale (WAS) by
      patients, nurses and physicians on 8 admission units before and after the
      introduction of the partial open door system. On average, on 45% of the days on
      which the units could have been potentially open, they were indeed at least
      temporarily open. Several significant changes in the WAS scores, mostly in
      desirable direction, were registered. However, close relationship with the
      partial opening of the units could be substantiated only with regard to the scale
      "praxis orientation"; still a positive result. No unequivocal relationships could
      be demonstrated between the introduction of the partial open door system and the
      changes in the frequency of "special events".

PMID- 9036400
TI  - [Department social climate on mixed sex and segregated acute psychiatric units.
      Results of a survey].
AB  - The segregation of sexes in an acute psychiatric unit was followed up by means of
      a research survey. Patients and staff members were questioned about the ward
      climate before and after changing the admission procedure. The male patients
      merely noticed a decreased influence of sexual problems on the ward atmosphere.
      The female patients evaluated the new ward for women as an improvement. In
      particular, assistance and clarity of conditions were more positively assessed.
      The staff members of the previous open ward noticed a significant increase in
      annoyance and aggression after closing the ward and segregation of the sexes. In
      general, segregation of the sexes did not result in deterioration of the ward
      atmosphere.

PMID- 9036401
TI  - [Attitude to schizophrenia: a survey of male and female journalists].

PMID- 9036402
TI  - [Differential diagnosis of tuberculous meningoencephalitis, schizophrenic
      psychosis and severe conflict reaction].

PMID- 9036403
TI  - [Psychiatric disorders after a single 3,4-methylenedioxyethamphetamine (MDE,
      "Eve") and tetrahydrocannabinol (cannabis) use].
AB  - We report on a single intake of 3,3-methylenedioxyethamphetamine (MDE, "Eve") and
      tetrahydrocannabinol (cannabis). Because of the increasing abuse of "designer
      drugs" and the rare reports on MDE the psychopathology after intake of MDE and
      cannabis is presented.

PMID- 9036404
TI  - [Is the new guardianship law regarding alcoholic patients therapeutically useful?
      A case example].
AB  - Although treatment outcome in alcoholism is good and well documented, many
      patients are not sufficiently motivated for participating in a treatment program.
      The following case-report illustrates the example of a young male alcoholic
      suffering from decompensated liver cirrhoses without motivation for a long-term
      treatment. The positive effects of the new guidelines of the laws regulating
      custody and civil commitment are shown and discussed.

PMID- 9036405
TI  - [A schizophrenic patient in a therapy group].

PMID- 9036406
TI  - [Chronic intrafamilial ambivalence as precipitant of transitory dissociative
      disorder (pseudohallucination) in an adolescent patient].

PMID- 9036408
TI  - [Changes in the blood picture with combination carbamazepine, perazine and
      antibiotic treatment].

PMID- 9036407
TI  - [Arson as a symptom of borderline personality disorder].

PMID- 9036409
TI  - [Long-term inpatient therapy of schizoid personality disorder].

PMID- 9036410
TI  - [Social and familial aspects in physical abuse and sexual abuse experiences in
      childhood from the viewpoint of young adults. Selected results of the Hamburg
      Study (1)].
AB  - The basic assumption of this investigation is that sexual abuse and physical
      maltreatment should not be investigated in isolation. Young adults have been
      asked to participate in a study on body and sexual experiences in childhood. It
      was tested how sexually abused and/or physically maltreated women and men
      differentiate from those without this experiences. 23% out of 616 women were
      classified as sexually abused and 28% as physically maltreated. 4% of the 452 men
      were allocated as sexually abused and 14% as physical maltreated. Aside from
      assessing group differences, the main purpose of this study was to test which
      variables would predict sexual abuse and physical maltreatment in multivariate
      analysis. In this part of the study, the relevance of socioeconomic and family
      factors for the statistical prediction of sexual abuse and physical maltreatment
      in multivariate analysis are presented.

PMID- 9036411
TI  - [Function and structure of families with chronically ill children].
AB  - In modern medicine especially the sick child often points out the limits of the
      psychosocial potentialities. This project investigates the function, structure,
      coping mechanisms, power and weakness of families with chronically ill children.
      We investigated 28 children from the nephrological ward and 55 patients from the
      cardiological department and also their families with the FAM III and compared
      the obtained T-scores with the results of the control-group (76 families, t-test,
      analysis of variance). Families with patients after renal transplantation (NTX)
      pointed out significant worse T-scores than the group with patients on CAPD or
      with preterminal renal insufficiency and CG (p < 0.05). Within the cardiological
      groups the differences were not statistically significant, on the other hand the
      group with patients before heart-operation and the group with patients after
      palliative heart-operation had better T-scores than the CT (p < 0.05). These
      results demonstrate that families with children suffering from a chronic renal or
      heart disease mobilize substantial resources to cope with these problems. By
      contrast the results of the families with patients after NTX or successful heart
      surgery are significant worse than the control-group and the other investigated
      patients groups. Our results come to the conclusion that especially after
      successful NTX or heart-surgery a psychosocial care of these families is
      necessary.

PMID- 9036412
TI  - [Quality of life and coping with illness in patients with acute myeloid
      leukemia].
AB  - Advances in chemotherapy significantly prolong survival of patients with acute
      myeloid leukemia (AML) and may cure a significant percentage of patients.
      Therefore, the assessment of quality of life (QL) of patients undergoing
      chemotherapy is of growing interest. This study was designed to evaluate QL in
      patients with AML treated according to the protocol of the German AML-Cooperative
      Group (Munster, FRG). Based on conceptual, methodological and practical criteria,
      the EORTC-QLQ C 30 questionnaire was used. In addition, patients' coping
      strategies were assessed by the FQCI. Patients' individual perception of their
      disease and therapy was evaluated by a semi-structured interview. Currently, 61
      patients are enrolled in the protocol. For those patients having completed the
      course of inpatient treatment, individual assessment of Global Health Status and
      Subjective QL improves significantly. The content analysis of the interviews
      shows to what extent aspects of the inpatient setting influence patients' QL.
      Although only a minority of patients with AML remain in continuous complete
      remission, the evaluation of QL in patients undergoing treatment shows that
      subjective benefit outweighs the effects of antileukemic therapy.

PMID- 9036413
TI  - [Conversion disorder: psychosomatic aspects instead of psychogenesis?].
AB  - The main emphasis of this paper is on a critique of the idea still current in
      psycho-analysis as well as in psychiatry that conversion can be seen as a purely
      psychogenic process. This reductionist idea is responsible for some of the
      difficulties clinicians encounter in their work with patients with a suspected
      conversion disorder; it may be a consequence of a hysterical structure of this
      theory. A coherent theory of the psycho-somatic phenomenon of conversion has to
      proceed in a non-reductionist methodology comprising psychological as well as
      physiological levels of description and explanation. In this paper, these
      hypotheses are developed in three dimensions: a) concerning clinical encounters
      with patients with "pseudoneurological" symptoms; b) looking at the historical
      development of the Freudian concept of conversion between 1894 and 1916/17, and
      c) theoretically, including some concepts of cognitive neuroscience.

PMID- 9036414
TI  - [Effects of patient education in type II diabetic patients after clinic
      admission. Results of a 3 month catamnesis after new patient-centered education].
AB  - The success of structured teaching programs trying to enable NIDDM patients to
      carry out effective self-management of their diabetes often does not last very
      long. Only few type-II-diabetes patients are able to both, control their
      nutritional behaviour, and maintain metabolic control in the long run. We added
      therefore a patient-centered motivational support training programme to a regular
      teaching programme. The underlying hypotheses being that the cognitions of
      patients with NIDDM frequently cause non-compliant behaviour concerning diet and
      sports. The motivational training programme aimed at systematic modification of
      patients' cognitions. 43 type-II-diabetes patients took part in a test of the
      motivationally supplemented diabetes training. As a result of the training a
      range of variables such as quality of life, glycosylated haemoglobin, body
      weight, etc. strongly supported the superiority of the motivational supplemented
      teaching programme. Unfortunately, effects of the motivational training programme
      disappeared within three month after completion of the training. These findings
      suggest that further support is needed to maintain the achieved level of
      motivation after the training. To address this problem we designed a self-help
      programme to be worked by the patients themselves whenever metabolic control
      cannot be maintained.

PMID- 9036415
TI  - [Osteomyelitis. A pathomorphologic overview].
AB  - Osteomyelitis is an infection of the bone marrow caused by both non-specific and
      specific agents. Non-specific endogenic osteomyelitis represents the most
      frequent form, followed by the specific form caused by Mycobacterium tuberculosis
      infection. Typically, the non-specific form occurs in children and young adults,
      and the sites most frequently affected are the distal and the proximal ends of
      the tibia and femur. In tuberculosis, osteomyelitis is predominantly located in
      the vertebral bodies. In rare cases osteomyelitis can be caused by viruses, fungi
      or echinococcus. It may also occur as so-called acute endogenic osteomyelitis,
      such as plasmocellular osteomyelitis and Brodie's abscess. Histologically, dense
      infiltration of leucocytes, granulation tissue and bone sequesters can be seen.
      In tuberculosis granulomas with central necrosis, epithelioid cells and giant
      cells of Langhans type are characteristically found. Most forms of acute
      osteomyelitis can be successfully treated with antibiotics, leading to complete
      healing without complications. Only a few reported cases develop into a
      secondary, chronic form.

PMID- 9036416
TI  - [Diagnostic imaging of acute and chronic osteomyelitis].
AB  - For the diagnosis of acute and chronic osteomyelitis imaging methods have become
      essential. This paper reviews the potential of the different imaging modalities.
      When there is clinical suspicion of acute osteomyelitis plain films are still the
      mainstay of diagnosis. In newborns and young children this primary diagnostic
      modality will be supplemented by sonography. If there is a need for further
      imaging, MRI and the different scintigraphic methods may be used interchangeably.
      However, for the spine and other complex anatomical regions MRI is preferred. In
      contrast, three-phase bone scanning is mostly accepted as the primary additional
      tool to radiography and sonography in the newborn and in small children. If an
      abscess is suspected, MRI is the primary imaging modality. In cases of chronic
      osteomyelitis radiography still forms the basis for obtaining information about
      the bone. Further imaging is regularly needed, not only because of its diagnostic
      value but also because radiographs do not demonstrate the extent of lesions
      correctly. The evaluation of disease extent in bone is a domain of MRI, while
      scintigraphic methods, like 111In leucocyte scintigraphy and MRI, are of
      equivalent diagnostic value. CT may have its role in disclosing a sequestrum when
      radiographs and MRI are equivocal.

PMID- 9036417
TI  - [Infectious spondylitis in adults].
AB  - In adults, infectious spondylitis is a rare but severe disease, caused by a
      bacterial thrombus in tissue of reduced resistance. In conventional radiographs
      initial findings are a narrowing of the intervertebral space, local osteoporosis
      and poorly defined erosive borders of the vertebral endplates. These changes can
      be found at least three to six weeks after the onset of disease. However, in
      Szintigraphy and MRT pathologic alterations are evident after ten to twelve days.
      Thus, early diagnosis and treatment becomes possible. In early stages of the
      disease a localized lysis surrounded by a reactive sclerosis appears in
      predisposed areas of the vertebral body (subchondral, anterobasal, ventral,
      central). Apparently, a soft tissue tumor is associated. Sclerosis and reduction
      of the soft tissue tumor are the first signs of repair processes. After at least
      12 weeks, computed tomography can reveal typical sintering of the vertebral body
      and occasionally the development of a bony sequester. In addition, MRT as well as
      CT can be helpful in the detection and localization of complications as abscesses
      or affection of the vertebral canal. The tuberculous spondylitis can sometimes
      cause difficulties in differential diagnosis. Clinical findings, affection of
      several vertebral bodies, large soft tissue tumors with appearance of
      calcification as well as not typical locations are strongly suggestive of
      tuberculous spondylitis, but these findings are not specific of the disease.
      Degenerative disorders such as erosive osteochondrosis or changing due to chronic
      dialysis (e.g. amyloid or crystal arthropathies) may cause even more problems in
      differential diagnosis. Typical for a blastomatous process is the integrity of
      the interverebral disc space, which is a rare finding in spondylitis.

PMID- 9036418
TI  - [Diagnostic imaging in osteomyelitis. Characteristics in childhood].
AB  - The prognosis of acute hematogenous osteomyelitis in children is mainly
      influenced by early diagnosis and prompt initiation of antibiotic and surgical
      therapy. In this age group, two forms of manifestation are differentiated:
      osteomyelitis in infants up to 18 months and juvenile osteomyelitis until the
      closure of the epiphyseal plate. Osteomyelitis in infants is often accompanied by
      septic arthritis of the adjacent joint. In juvenile osteomyelitis, the disease is
      mostly confined to the metaphysis. Plain films and ultrasonography represent the
      basic imaging modalities. Depending on the age of the child, the clinical course
      of the disease and the availability of the various methods, MRI and multiphase
      bone scintigraphy can be performed for further imaging. CT is of only limited
      value and should only be used for special cases concerning chronic osteomyelitis.

PMID- 9036419
TI  - [Nuclear medicine diagnosis of osteomyelitis].
AB  - Scintigraphic imaging identifies pathophysiological processes; in other words it
      assesses regional perfusion, permeability, leukocytic accumulation and bone
      turnover. These processes precede morphological changes and this accounts for the
      high sensitivity of nuclear medicine procedures as well as the low specificity
      for the differential diagnosis of different diseases with similar
      pathophysiological characteristics. This review (1) describes and evaluates the
      currently used scintigraphic procedures, (2) suggests their differential use in
      certain clinical settings in comparison with alternative radiological methods and
      (3) addresses new developments in diagnosis using nuclear medicine procedures. In
      summary, we advise dynamic bone scanning as a primary scintigraphic
      investigation. A negative scan excludes osteomyelitis in most cases. The
      comparison is made with conventional radiology and clinical history. In cases
      with short clinical histories (= granulocytic inflammation), leukocyte
      scintigraphy should be the next diagnostic step; in chronic processes
      (lymphomonocytic inflammation), gallium scintigraphy is advisable. Other
      scintigraphic methods might be of additional use in experienced hands. SPECT is
      useful for clarifying inconclusive planar scans of the head, spine and large
      joints.

PMID- 9036420
TI  - [Osteomyelitis. Clinical aspects, diagnosis and therapy].
AB  - In this paper the basic features of acute, subacute and chronic types of
      osteomyelitis, skeletal tuberculosis and some special forms of osteomyelitis are
      described. The diagnosis of osteomyelitis is established using clinical signs and
      symptoms, culture studies, laboratory studies and radiological signs. The common
      conservative and surgical treatments are discussed. In the treatment of
      posttraumatic/postoperative osteitis severe problems are encountered as a result
      of an increasing number of orthopaedic traumatologic surgical techniques using a
      variety of implants and because of a generally increasing occurrence of
      multiresistant strains. Thanks to modern treatment and the increased use of
      antibiotics, a considerable decrease in morbidity and mortality is observed.
      Despite this improved prognosis, an established infection remains one of the most
      challenging problems for the orthopaedic surgeon.

PMID- 9036421
TI  - [Comparison between direct radiographic enlargement and mammography technique in
      detection of osseous changes of the hand skeleton in hyperparathyroidism].
AB  - PURPOSE: To compare direct magnification radiography and mammographic film-screen
      systems in osseous changes of the hand in hyperparathyroidism. MATERIALS AND
      METHODS: The hands of 60 patients who were suspected to have primary (5),
      secondary or tertiary (both 55) hyperparathyroidism were evaluated with direct
      magnification radiography and a mammographic film-screen system (S12.5).
      Posterior-anterior views of each hand were obtained with both techniques. The
      magnification radiographs were made with a focal spot size of 40 or 60 microns,
      digital luminescence radiography (S600/1200), and a x 6 or 8 magnification. The
      240 films were evaluated for subperiosteal, intracortical and endosteal
      resorptive changes by five radiologists using a grading according to five levels
      of confidence. RESULTS: A significant improvement (p < 0.05) in the diagnosis of
      periosteal and intracortical bone resorption was shown, but no significant
      changes in endosteal resorption with direct magnification radiography. As
      compared to mammographic film-screen systems, magnification radiography improved
      the diagnostic accuracy (24%). The time needed for the evaluation of periosteal
      and intracortical bone resorption was shortened with direct magnification
      radiography (-4%/ -15%), and the time for giving the diagnosis decreased (-10%).

PMID- 9036422
TI  - [Magnetic resonance tomography of liver cirrhosis in a 17-year-old patient. Liver
      cirrhosis in hepatolenticular degeneration].

PMID- 9036423
TI  - [Facial and orbital soft tissue emphysema after self-injury].

PMID- 9036424
TI  - [Spiral CT angiography in stenoses of the middle cerebral artery].
AB  - INTRODUCTION: Transcranial Doppler ultrasonography (TCD) and magnetic resonance
      angiography (MRA) are well-established techniques for ascertaining intracranial
      obstructive artery disease. The short examination time required for additional
      helical CT angiography (CTA) allows quick management of emergency patients
      already undergoing native CT. However, today the ability of CTA to detect
      stenoses of the middle cerebral artery (MCA) has not been proven. To analyse the
      value of CTA in the classification of atherosclerotic disease 23 MCA stenoses
      confirmed by TCD and MRA were investigated. METHODS: CTA was performed on a
      Hispeed advantage scanner (GE) using a bolus injection of 70 ml KM and 40 ml NaCl
      with a flow rate of 2.5 ml/s, a thickness of 1 mm, a pitch of 1.5 and a 1 mm
      increment. CTA was presented as maximum intensity projection (MIP) and as multi
      projection volume reconstruction (MPVR). A three-step classification of stenosis
      was compared with the results of TCD and MRA. RESULTS: Good opacification of the
      MCA was achieved in M1 and M2 segments in all patients. Classification of
      stenosis by CTA agreed with MRA and TCD in 14 cases; 7 stenoses were assigned to
      a lower classification by CTA. Two low-grade stenoses could not be proven by CTA.
      Although MIP and MPVR yield the same result in stenosis classification MPVR
      showed a sharper image quality. In contrast to MRA, veins were highly opacified
      in CTA. Artery and vein were sometimes superimposed, which had to be avoided by
      changing the projection angle. CONCLUSION: Medium- and high-grade MCA stenoses
      can be demonstrated by CTA quickly and reliably. Compared to MRA and TCD, CTA
      provides lower grading of stenosis.

PMID- 9036425
TI  - [CT angiography in dissections of the internal carotid artery. Value of a new
      examination technique in comparison with DSA and Doppler ultrasound].
AB  - PURPOSE: To evaluate the role of CT angiography (CTA) in the diagnosis of
      dissection of the internal carotid artery (ICA). METHODS: In 21 patients who were
      clinically or sonographically suspected of having a dissection of the ICA, we
      performed CTA covering the extracranial course of the ICA. Our technique included
      spiral scanning (Picker PQ 2000), slice thickness 3 mm, index 1.5 mm, pitch
      factor 1.25, tube voltage 130 kV, amperage 125 mA, i.v. bolus injection of 100 ml
      nonionic contrast medium, injection rate 4 ml/s and scan delay 15 s. Spiral data
      were processed using a workstation (Picker Voxel Q) to calculate 3D
      "angiographic" reconstructions, maximal intensity projections and multiplanar
      reconstructions. In 20 of the 21 patients transfemoral angiography was performed,
      and in all patients cw-Doppler ultrasonography of the carotid arteries was
      performed. RESULTS: Sensitivity of CTA in acute extracranial dissection of the
      ICA was 100% (14/14). One patient had a pseudoaneurysm of the ICA, two patients
      had excessive kinking and one patient showed an atheromatous carotid ulcer. DSA
      could confirm this in all cases. One intracranial ICA dissection, not covered by
      the scan field, was missed by CTA. CTA source images demonstrated mural
      thickening and eccentric luminal narrowing in cases of dissection. 3D
      reconstructions showed tapering of the ICA. CONCLUSION: CTA is a reliable tool in
      the diagnosis of ICA dissection. Further studies comparing CTA, MRI and duplex
      ultrasound are necessary.

PMID- 9036426
TI  - [CT angiography in basilar artery thrombosis. Initial experiences].
AB  - BACKGROUND AND PURPOSE: Without recanalisation, acute basilar artery (BA)
      occlusion has a mortality of 90%, which is reduced to 50% if recanalisation is
      achieved. Fast diagnosis of BA occlusion is necessary in order to start
      thrombolytic therapy without delay. We wanted to assess the role of CT
      angiography (CTA) in the diagnostic evaluation of suspected acute BA occlusion.
      MATERIALS AND METHODS: Ten patients with clinically suspected BA occlusion were
      examined with conventional CT and spiral CT angiography. Spiral scanning extended
      from the foramen magnum to the tip of the basilar artery. For CTA, 130 ml of
      nonionic contrast media were injected into an antecubital vein. In four patients,
      transfemoral digital subtraction angiography (DSA) was additionally performed.
      All but one patient had a follow-up CT examination the next day. RESULTS: CTA
      demonstrated BA occlusion in six patients and a partially thrombosed
      megadolichobasilar artery in one patient. In four of the six patients with CT
      angiographically diagnosed BA occlusion, an additional DSA was performed, which
      confirmed the CTA findings. In three patients the BA showed normal intravasal
      contrast, and follow-up CT did not show infarctions in the vertebrobasilar
      territory. CONCLUSION: Although the number of cases is still small, CTA seems to
      be a promising method for the rapid diagnosis of BA occlusion. It may become a
      valuable tool for therapy decisions in acute BA occlusions.

PMID- 9036427
TI  - [Value of CT-angiography in diagnosis of cerebral sinus and venous thromboses].
AB  - Dural sinus thrombosis is not uncommon. Due to the nonspecific symptomatology, as
      well as the manifold etiology, clinical diagnosis may be difficult. In these
      cases imaging procedures are frequently crucial in deciding how to proceed and
      how to treat. The aim of our study was to evaluate the diagnostic utility of
      helical CT in the detection of dural sinus thrombosis. In 20 patients with
      clinically suspected thrombosis CT angiography was performed. In 6 patients dural
      sinus thrombosis was diagnosed. In order to acquire also arterial vessels, a
      short delay of about 22 s after the onset of the application of contrast medium
      was selected. By this method we found an occlusion of the MCA in two patients
      with clinically suspected sinus thrombosis. In all patients the transverse slices
      and the multiplanar reconstructions showed filling defects or an "empty delta"
      sign. With irregular outlines the thrombus could be depicted over the complete
      course of the sinus. The MIP reconstructions were particularly helpful in the
      evaluation of the vessel anatomy and the pathological collateral venous drainage.
      In three patients MR angiograms were available for comparison. The smaller veins,
      such as the v. vermis inferior, were less clearly depicted than in CT
      angiography. CT angiography is a fast and reliable method to exclude or verify a
      sinus thrombosis. It can be performed immediately after non-enhanced CT.
      According to our present experience CT angiography is sufficient for the
      diagnosis of a sinus thrombosis.

PMID- 9036428
TI  - [CT-angiography in planning stereotaxic biopsies].
AB  - Twenty-one patients referred for stereotactic biopsy were studied by CT
      angiography. Helical CT with 1 mm collimation was obtained (pitch of 1:1).
      Multiplanar reconstructions were performed; maximum intensity projections and
      shaded-surface displays were generated by connectivity-based editing tools. The
      visualization of cerebral vessels was excellent. No further conventional
      angiography was needed. Improved information was obtained about localization of
      the intracranial lesion and its relationship to neighboring vessels. No bleeding
      complications were detected by CT after stereotactic biopsy.

PMID- 9036429
TI  - [Magnetic resonance angiography and magnetic resonance tomography in dissection
      of the vertebral artery].
AB  - Vertebral artery dissection (VAD) is an important cause of posterior circulation
      stroke in young adults. Initial symptoms are often non-specific and diagnostic
      arteriography is not performed until neurological deficits are obvious. Since
      magnetic resonance tomography (MRT) is superior in the diagnosis of
      vertebrobasilar ischemia, we retrospectively analyzed the role of MRT and MR
      angiography (MRA) in the detection of dissections of the vertebral artery.
      Between 1989 and 1995 we identified 24 patients with a vertebral artery
      dissection and 1 patient with a basilar artery dissection (8 females and 17
      males, 23-60 years of age, mean 41.2 years). The diagnosis of VAD (14 left VAD, 9
      right VAD, 1 bilateral VAD, 1 basilar artery dissection) was established by
      specific arteriographical findings (DSA) or clinical and neuroradiological
      course. All patients underwent a combined MRT/MRA examination protocol at 1.5T
      that consisted of spin-echo imaging and time of flight MRA of the intra- and
      extracranial arteries using 2D Flash and 3D Fisp sequences. The MRT/MRA findings
      were correlated to DSA and ultrasound results. During the acute and subacute
      stage, MRT/MRA revealed abnormal findings in 21 of 22 dissected vessels (95.5%).
      There was one false-negative MRT/MRA in a patient with a V1 dissection (intimal
      flap without peripheral flow disturbances). In 7/22 VAD the MRT/MRA findings were
      rated specific (double lumen n = 1, mural hematoma n = 4, pseudoaneurysm n = 2).
      DAS was sensitive in 100% and ultrasound in 77.3%. Specific results were obtained
      by DSA in 8/ 22 VAD (36.4%) and in 7/22 VAD (30.4%) by MRT/MRA. When MRT/MRA and
      DSA results were combined, the specific findings increased to 43.5%. Follow-up
      examinations revealed recanalization in 52% of initially stenosed or occluded
      vertebral arteries; four patients developed a pseudoaneurysm, and two of them
      underwent ligation of the VAD. With this retrospective approach, we were able to
      show a high sensitivity of MRT/ MRA for the presence of disturbed flow in the
      dissected vertebral artery. The MRA projections tended to overestimate stenosis
      and were inferior to DSA in the appreciation of irregularities of the vessel
      wall. Identification of high-grade stenosis, especially in the presence of distal
      occlusion, was improved on the MRA source images. During the acute and subacute
      stage, the diagnosis of luminal thrombus can be difficult, because signal
      ambiguities exist between hemoglobin breakdown products and flow effects and
      adjacent fat tissues. The differentiation between luminal thrombus and mural
      hematoma requires interpretation of MRA source images, together with flow
      compensated spin-echo images. Additional fat suppressed images and flow
      presaturation may be required at the appropriate levels. The identification of
      mural hematoma is important, because this finding is considered specific and
      cannot be obtained with DSA. There is a complementary role of MRT/MRA and DSA for
      an improved overall specificity for vertebral artery dissection. A negative
      MRT/MRA result in a patient with appropriate symptoms, however, cannot exclude a
      dissection and should prompt DSA. On the other hand, a suggestive MRT/MRA result
      in the appropriate clinical context can replace DSA. The advantage of MRT/MRA is
      that the method offers a simultaneous diagnosis of posterior fossa ischemia and
      vertebral artery abnormalities. Therefore, MRT/MRA should be recommended in
      patients with suspected VAD and especially in those who have no definite
      neurological deficit. These patients will benefit greatly from early diagnosis
      and therapy. The fact that all our patients were diagnosed after neurological
      symptoms and that 64% of them have residual deficits gives an ethical and
      economical rationale for advocating early MRT/MRA in these patients.

PMID- 9036430
TI  - [Dysembryoplastic neuroepithelial tumor (DNT). Pattern of neuroradiologic
      findings].
AB  - Dysembryoplastic neuroepithelial tumors (DNT) were first described as a new tumor
      entity by Daumas-Duport et al. in 1988 and were introduced into the revised WHO
      classification of brain tumors in 1993. The purpose of this study was to work out
      neuroradiological CT and MRT patterns of DNT. Five patients, aged 11-61 years
      (three female, two male) underwent complete presurgical neuroradiological
      exploration (5 CT, 4 MRT investigations, 2 angiography) because of brain tumor.
      Four cases complained of seizures and one of occipital-located headache. Total
      microsurgical excision was achieved in two cases. Two further lesions were
      resected subtotally after stereotactic biopsy diagnosis. In one case,
      stereotactic biopsy alone was carried out. All DNTs were localized cortically:
      two frontobasal medial in the gyrus rectus, two temporobasal in the gyrus
      occipitotemporalis lateralis and one infratentorial in the lobus caudalis
      cerebelli. They were sharply demarcated from the surrounding brain tissue.
      Cortical localization was better visualized by MRT, especially on coronal and
      sagittal images. CT scans showed a hypodense lesion, MRT a high-signal intensity
      in T2, low signal in T1 and in proton-weighted images a hyperintense rim with a
      slightly hyperintense small cyst. The multinodular tumor architecture was best
      seen in MRT. Two DNTs presented partial contrast enhancement, while three DNTs
      did not take up contrast. In two lesions there were focal calcifications. The
      infratentorial DNT was associated with a bony defect of the tabula interna into
      which the tumor expanded. Two angiographies showed no pathological tumor
      neovascularization. A hypodense sharply demarcated lesion with a multinodular
      pattern in MRT with cortical location and without space-occupying signs is, in
      combination with the clinical symptom of epileptic seizures, highly suggestive of
      DNT. As our results demonstrate, DNT can also occur in the infratentorial space.

PMID- 9036431
TI  - [Inflammatory facial paralysis in MRI. An overview].
AB  - In inflammatory peripheral facial nerve palsy pathologically intense, linear and
      smooth enhancement of the distal intrameatal nerve segment can always be observed
      on T1-w- SE- MR sequences. The other nerve segments often present with a
      pathological enhancement as well. On T2-w- SE sequences, a thickening of the
      distal intrameatal nerve segment can be observed. The pathological enhancement
      persists over weeks and months; even in patients with complete clinical recovery,
      a persistent enhancement of the distal intrameatal nerve segment can be
      demonstrated. No correlation can be established between the intensity of the
      enhancement, the clinical condition and the electrophysiological data on
      electroneurography. The persistent enhancement of the different nerve segments is
      due to a long-lasting breakdown of the blood-peripheral nerve-barrier related to
      the process of degeneration and regeneration of the facial nerve in inflammatory
      palsy.

PMID- 9036432
TI  - [Inflammatory diseases of the spinal cord and spinal nerve roots in the MRI].
AB  - PURPOSE: To evaluate characteristic and reliable MRI patterns of different
      inflammatory lesions of the spinal cord and the nerve roots in immunologically
      compromised and immunologically competent patients in order to be able to
      establish a correct diagnosis based on MRI findings. MATERIAL AND METHODS: The
      MRI examinations of 52 patients (27 men, 25 women, mean age 38.5 years, range 14
      75 years) with proven inflammatory lesions (39 patients) or tumorous/postactinic
      lesions of the spinal cord (6 patients) and vascular malformations of the spinal
      cord (7 patients) were retrospectively analyzed. All examinations were performed
      on a 1.5 T MR unit, using bi- or triplanar T1-w pre- and postcontrast as well as
      T2-w SE sequences. Additionally, a review of the common medical literature
      concerning inflammatory lesions of the spinal cord was included. RESULTS:
      Clinical and radiological examinations allow a subdivision of inflammations of
      the spinal cord and the nerve roots into (meningoradiculo) myelitis and
      meningoradiculo (myelitis) in immunologically suppressed or competent patients.
      The MRI patterns of these two inflammatory subtypes vary: meningoradiculitis
      presents with an enhancement of the nerve roots and the leptomeninges; myelitis
      itself is characterized by single or multiple, diffuse or multifocal, with or
      without nodular, patchy or diffusely enhancing intramedullary lesions, with or
      without thickening of the cord and leptomeningeal inflammation. This
      differentiation helps to determine the underlying etiology in some of the
      patients. The immunologically suppressed patient suffers from viral infections
      (especially herpes simplex, varicella-zoster virus, cytomegalovirus), bacterinal
      infections (tuberculosis), but rarely from parasitic infections. The
      immunologically competent patient suffers from bacterial (borreliosis), but
      rarely viral infections, sarcoidosis and demyelinating diseases. Idiopathic
      myelitis is also common. CONCLUSIONS: Secondary ischemic and demyelinating
      processes result in a complex morphology of inflammatory lesions on MRI, and
      therefore the whole spectrum of demyelinating, ischemic and inflammatory lesions
      has to be included in the differential diagnosis. Even tumors may imitate
      inflammatory myelitis and radiculitis. Most commonly, meningoradiculitis can be
      separated from myelitis. A reliable diagnosis of a specific inflammatory lesion
      is difficult and is mostly achieved in patients with multiple sclerosis and in
      patients with HIV-associated cytomegalovirus infection.

PMID- 9036433
TI  - [Rare intracranial plasmacytoma manifestations. Case reports and review of the
      literature in diffuse plasmocytoma, in primary solitary extramedullary
      plasmacytoma in in primary solitary osseous plasmacytoma].
AB  - Plasmacytomas can be divided into multiple, solitary osseous and solitary
      extraosseous/extramedullary plasmacytomas. Intracranial plasmacytomas of the
      dura, leptomeninx and cerebrum are well known from the literature. They are
      manifestations of multiple myeloma, intracranial extramedullary plasmacytoma or
      metastatic disease of extramedullary plasmacytoma in distant locations. We
      describe a cerebellar manifestation of a solitary plasmacytoma of the bone, and a
      leptomeningeal carcinomatosis of a multiple plasmacytoma. A summary of the
      literature concerning intracranial plasmacytomas is given. Dural manifestations
      of plasmacytoma have the same features as meningiomas in CT or MRI. Cerebral or
      cerebellar manifestations cannot be differentiated from brain tumors by means of
      CT or MRI. In CT, plasmacytomas show high-density lesions. T2w-MRI reveals a low
      intensity lesion. In T1w-MRI, intense homogeneous contrast enhancement can be
      demonstrated.

PMID- 9036434
TI  - [Incidence of postmyelography syndrome and postmyelography complaints after
      lumbar puncture with the Sprotte pencil-like needle in comparison with the
      Quincke needle].
AB  - PURPOSE: Myelography in combination with a postmyelography CT is an important
      presurgical examination because of its excellent visualisation of the disc, the
      bone and the contrast-filled dura. Side effects after myelography can be observed
      in up to 50% of patients. The pathophysiological mechanism is thought to be
      increased cerebrospinal fluid leakage at the puncture site. Since the
      introduction by Sprotte in 1979 of the pencil-point needle, a modification of
      Whitacre's needle, fewer complaints after lumbar puncture have been reported. The
      aim of the study was to examine the influence of two types of needle points and
      the temperature (37 degrees C vs 21 degrees C) of the contrast medium (CM;
      iotrolan, Isovist) on the incidence of side effects of lumbar puncture for
      myelography. MATERIAL AND METHODS: In a prospective randomized trial the
      incidence of complaints after lumbar puncture with intrathecal CM application was
      evaluated by the use of a 21-G pencil-point needle as modified by Sprotte
      compared to our usual 22-G needle with a Quincke bevel. Some 412 patients (201
      female, 211 male; mean age 54.05 +/- 7.4 years) were investigated. Directly after
      examination and 1. 3 and 5 days later the patients were questioned about
      complaints (headache, neck stiffness nausea, vomiting, buzzing in the ear and
      dizziness). The results were tested by the chi square test. RESULTS: A
      significantly lower incidence of complaints was seen after lumbar puncture with
      the pencil-point needle/Quincke needle (headache: 6.3%/18.9%, P < 0.0001;
      headache lasting 3 days: 0.5%/7.8%, P < 0.0001; headache lasting 5 days: 0%/2.4%,
      P = 0.0305; nausea: 0%/4.9%, P = 0.0009; vomiting: 0%/3.4%, P = 0.0009;
      dizziness: 0%/3.4%, P = 0.0074; neck stiffness: 0%/3.4%, P = 0.0074). The
      temperature of the CM had no influence on the complaints. No influence was seen
      on the quality of the myelogram. No relation to sex and age was found.
      CONCLUSION: Complaints after lumbar puncture and myelography are caused by the
      cerebrospinal fluid leakage at the puncture site. The incidence of side effects
      related to this leakage can be reduced by using a pencil-point needle. The
      temperature of the CM has no influence on the complaints.

PMID- 9036435
TI  - [Etiology of cervicobrachialgia with paralysis and hypesthesia in C7 and C8
      dermatomes. Rheumatoid arthritis of the intervertebral joints C6/7 and C7/Th1
      with inflammatory intraspinal and intraforminal pannus formation].

PMID- 9036436
TI  - [The Italian Association of Radiology (SIRM) and the industrial sector for
      scientific research: potential development].

PMID- 9036437
TI  - [Uterine and tubal-peritoneal factors in infertility: comparison of radiologic
      and endoscopic techniques].

PMID- 9036438
TI  - [The determination of BB genotype of vitamin D receptors identifies patients at
      risk for osteoporosis].
AB  - The gene responsible for peak bone mass has been recently identified as the gene
      coding for the Vitamin D Receptor (VDR); there exist two alleles, termed "B" and
      "b", determining a typical allelic polymorphism. We determined the VDR genotype
      of 50 young post-menopausal women (mean age: 56 years), and measured bone density
      by Dual Energy X ray Absorptiometry (DEXA) twice: at the beginning of the study
      and after one year. VDR genotype was determined using the DNA extracted from hair
      cells, thus avoiding the use of blood samples. The frequency of VDR genotypes (BB
      or bb homozygous; Bb heterozygous) was approximately the same in the two groups
      of subjects (i.e., normal controls and osteoporotic women). The bone density of
      normal subjects (36) was measured for the second time one year after the first
      measurement. All BB homozygous subjects showed significantly decreased bone
      density values; 50% of them showed values below 0.750 g/cm2 at the second
      measurement, thus being classified as osteoporotic. However, neither bb
      homozygous nor Bb heterozygous subjects showed any significant decrease in bone
      density values (about 4% of the initial value). Therefore, determining the VDR
      genotype was critical for identifying the subjects who were normal at the first
      measurement, but had markedly decreased bone density values later, thus being at
      risk of developing osteoporosis.

PMID- 9036439
TI  - [Aneurysmal bone cyst: diagnostic role of computerized tomography and magnetic
      resonance].
AB  - Aneurysmal bone cysts (ABC) are relatively uncommon benign expansile osteolytic
      lesions characterized by multiple cavities with serum-blood levels and delimited
      by a thin periosteal external border. The differential diagnosis is difficult to
      make with conventional radiography, while CT and MRI are elective techniques. Ten
      patients with ABC (7 central and 3 eccentric lesions) were examined with CT and
      MRI. Four cysts were localized at the proximal femur, 2 in calcaneal, 2 in
      vertebral (cervical and dorsal), 1 in tibial and 1 in iliac sites. Diagnostic
      criteria were the presence of fluid-fluid levels and a thin hyperdense peripheral
      border at CT, while hyperintense cavities on T2-weighted sequences, fluid-fluid
      levels, pseudodiverticular features and a low-signal border were found at MRI.
      Intralesional levels were detected in 9 patients at CT and in 10 at MRI; the 3
      peripheral cysts exhibited a hyperdense extraosseous border at CT, corresponding
      to the periosteal shell, considered a benignity sign. To conclude, CT and MRI,
      thanks to their high resolution, clearly depict the anatomopathologic features of
      ABC, thus allowing this type of lesion to be differentiated from other benign and
      malignant osteolytic lesions.

PMID- 9036440
TI  - [Myositis: diagnostic potential of a magnetic resonance unit with low intensity
      field (0.2 T)].
AB  - Magnetic Resonance Imaging (MRI) is a useful tool for demonstrating muscle
      changes in patients with inflammatory myopathies. We investigated the diagnostic
      capabilities of low field (0.2 T) MRI with a dedicated coil in a series of
      patients with an unquestionable clinical diagnosis of inflammatory myopathy.
      Infiltrating processes or muscle swelling are depicted as low-signal areas on T1
      weighted SE images and as high-signal areas on T2-weighted SE and short time
      inversion recovery (STIR) images. Fatty infiltration appears as a high-signal
      area within muscles on T1-weighted SE images. T2-weighted SE and STIR sequences
      are highly sensitive in demonstrating infiltrating processes or muscle swelling.
      The signal-to-noise ratio was higher on T2-weighted SE than on STIR images; on
      the other hand, fast STIR sequences can effectively reduce scan times. To
      conclude, low field MRI is a useful tool in the study of inflammatory myopathies
      thanks to its noninvasiveness and to the good depiction of muscle inflammation
      provided by T2-weighted SE and STIR images.

PMID- 9036441
TI  - [Stener lesions: ultrasonography assessment in 12 cases].
AB  - We investigated the ultrasonographic (US) features of Stener injury and thus the
      role of US in the diagnosis of this condition. Stener injuries are characterized
      by the tear of the cubital ligament system of the first metacarpophalangeal joint
      during hyperabduction. This condition may be associated with the displacement of
      the ligament proximal stump above the thumb adductor muscle. We examined 12
      patients (9 men and 3 women) with a clinical diagnosis of joint instability due
      to hyperabduction of the first metacarpophalangeal joint. All the US exams were
      performed with a linear probe (7.5-10 MHz); a 13-MHz probe was also used in 7
      patients. All the patients were submitted to radiography in the standard
      projections, to detect associated bone injuries. US allowed the identification of
      a round lesion surrounded by a hypoechoic halo, between the distal edge of the
      dorsal interosseous muscle of the first finger and the first metacarpal bone (the
      proper Stener injury) in 4/12 patients. In contrast, no typical sign was shown in
      the other 8 patients. US results were then compared with surgical findings. The
      diagnosis of proper Stener injury was surgically confirmed in 4 patients. Only 2
      patients with clinical signs of thumb instability, who were negative for Stener
      injuries at US, were submitted to surgery which demonstrated the ligament tear
      responsible for joint instability, but ruled out the displacement. To conclude,
      US must be integrated with clinical signs because this imaging method accurately
      shows complete tears with displaced proximal stump of the cubital ligament.

PMID- 9036442
TI  - [Preoperative assessment of Blount disease].
AB  - Osteochondrosis of the medial proximal tibial epiphyseal plate is known as Blount
      disease. To date, two types have been described: infantile and juvenile disease.
      Six patients (5 men and 1 woman, mean age: 7.2 years) affected with infantile
      Blount disease diagnosed with plain radiography were submitted to Magnetic
      Resonance Imaging (MRI) for preoperative lesion staging. The lesions were
      bilateral in 5 patients. According to Langenskiold classification, 2 patients
      were in stage II-III, 3 in stage III-IV and 1 in stage V-VI. Each patient
      underwent MRI of the more affected knee and 1 patient, who exhibited a more
      prominent metaphyseal beak, underwent CT of both knees. MRI depicted proximal
      tibia varus deformity and the degree of its angulation, which helped plan
      osteotomy; impaired growth of the medial portion of the proximal tibia involving
      physeal cartilage, metaphysis and epiphysis; alterations of menisci and ligaments
      (hypertrophic medial meniscus, medial collateral ligament laxity), the presence
      of bone bridges; the presence and integrity of unossified epiphysis and of
      chondral growth plate which was quite completely ossified in one case. To
      conclude, MRI is a completely atraumatic and noninvasive technique yielding many
      pieces of information necessary for the preoperative assessment of Blount
      disease.

PMID- 9036443
TI  - [Fluid attenuated inversion recovery sequences: indications in neuroradiology].
AB  - The acronym FLAIR refers to fluid attenuation inversion recovery sequences, which
      are T2-weighted MR pulse sequences with liquor signal saturation by a long TI.
      They are characterized by long TR and TE and therefore the acquisition time is
      very long in the conventional mode, while fast imaging (the Turbo mode) reduces
      acquisition time to less than 2 minutes. Our study was aimed at codifying the use
      of this type of sequence in neuroradiologic studies. All the exams were performed
      with an MR unit with a 1-Tesla magnetic field. We carried out 150 neuroradiologic
      exams with this pulse sequence on patients with cerebral, medullary or orbital
      conditions. This technique is very useful to study periventricular or cortical
      lesions in multiple sclerosis and in other multifocal cerebral conditions (e.g.,
      multiple metastases or lacunar infarcts), but we pointed out the following other
      advantages: better definition of the extent of infiltrative white matter lesions
      (i.e., gliomatosis cerebri and lymphomas), better differentiation of cystic from
      necrotic cavities and exact characterization of cortical damage in cerebral
      ischemic lesions (useful also for the differential diagnosis). Moreover, FLAIR
      pulse sequences could diagnose some globe conditions, such as amelanotic uveal
      melanomas and malformations with no need of contrast agent administration. In
      contrast, they were useless to study deep ischemic areas, solid neoplasms,
      hemorrhagic lesions, poroencephalic areas, intrinsic medullary lesions and intra
      orbital and extra-ocular conditions. In conclusion, the FLAIR technique is a
      major diagnostic tool in neuroradiologic MR studies because they overcome such
      limitations of Turbo SE PD sequences as blurring artifacts; moreover, their
      acquisition time is always very short. In some cases, FLAIR images are decisive
      for the diagnosis.

PMID- 9036444
TI  - [Functional mapping of the motor and primary sensorial cortex using magnetic
      resonance techniques. I. Preliminary data].
AB  - Functional Magnetic Resonance Imaging (fMRI) techniques sensitive to the local
      changes in blood flow, volume and oxygenation accompanying neuronal activation
      are powerful tools to investigate the human brain function. Experiments were
      performed on 10 right-handed healthy volunteers (age range: 20-39 years), using a
      1.5 T whole-body MRI system. Two oblique contiguous planes were investigated
      along the central sulcus of the left hemisphere. Functional images were acquired
      using a Gradient Echo sequence while the subjects repetitively performed
      sequential finger to thumb opposition movements of the right hand or mental
      imagery of a visual scene. Twelve images for each task were obtained over a 6-min
      experimental period; they were then analyzed with the software provided by the
      manufacturer. In all the subjects small areas were activated in both the
      precentral and postcentral gyrus, mean percentage signal increases during finger
      movement being 10.7% and 3.8%, respectively. These values are fairly higher than
      literature ones. However several factors, such as voxel volume, are involved in
      determining the measured signal increase during activation. Moreover, in most
      cases the software procedures provided with the MR equipment to analyze the
      functional images imply subjective choices. It is thus necessary to implement new
      software packages for the analysis of fMRI images to apply more appropriate
      statistical procedures and to obtain more homogeneous and objective final
      information.

PMID- 9036445
TI  - [Functional mapping of the motor and primary sensorial cortex using magnetic
      resonance techniques. II. Image analysis techniques].
AB  - Functional Magnetic Resonance Imaging (fMRI) techniques to investigate brain
      function are now available on clinical MR systems. However, the software packages
      provided with the MR equipment to analyze the functional images are often
      inadequate. In the present study, two registration algorithms for correcting
      motion artifacts and three procedures of statistical analysis (t-test,
      correlation analysis, Kolmogorov-Smirnov test) were compared using programs
      implemented on a graphic workstation. For both registration algorithms,
      transformation parameters for in plane translations and rotation of images were
      significantly affected by the task, being higher during sequential finger
      movements than during the control (visual imagery) condition. Regions of interest
      were identified on the anatomical images and their boundaries automatically
      projected on functional images. The number of significantly activated pixels in
      the pre- and postcentral areas was not significantly different after the
      registration with the two procedures. The percentage of pixels of the pre- and
      postcentral areas whose signal intensity was significantly different between the
      two tasks decreased with respect to the adopted threshold of significance as a
      power function. For an area identified outside the brain, the same relation was
      linear: no activated pixel was found for p < 0.001. The application of the t-test
      or of the correlation analysis yielded similar results. The analysis of the
      profile of mean normalized signal intensity showed higher increases in signal
      intensities during the motor task in the precentral gyrus than in the postcentral
      gyrus. This appears to be due to a greater number of activated pixels during
      motor performance. The application of registration procedures, the identification
      of the regions of interest on the basis of the anatomical images and appropriate
      statistical analyses allow a more detailed characterization of task-related
      activation.

PMID- 9036446
TI  - [Periodontal disease in patients with HIV infection. Radiographic study].
AB  - A painful and rapidly progressive form of periodontitis--involving both soft
      tissue and bone, with gingival bleeding and loss of teeth--was observed in HIV
      patients in the mid-80's. Today, there are few reports regarding the real
      incidence of periodontitis in HIV populations: however, it seems not as high as
      first supposed on discovering the disease, and bacterial plaque is moderate,
      compared with "conventional" periodontitis. Since there are few radiologic
      studies, the Authors report on the clinical-radiographic patterns of
      periodontitis in 20 HIV patients, compared to 20 normal controls. All the
      subjects were submitted to clinical-instrumental investigations (clinical tests,
      periodontal sampling, DMF index), and panoramic radiography. To assess
      periodontal disease severity, bone pocket depth is investigated radiographically,
      defined as the distance between the highest point of alveolar bone and root apex,
      at the mesial and distal aspects of all the teeth. We measured four alveolar
      quadrants, from the first premolar to the second molar. Statistical analysis was
      carried out with one way ANOVA test and non-parametric Kruskal-Willis's test;
      statistical significance is accepted at the probability level p < 0.05. Clinical
      radiographic results demonstrated minimal bone loss and little teeth mobility, in
      the early stage of disease; involvement of total gingival attachment with partial
      bone sequestration at muco-gingival line, in the moderate stage; severe bone loss
      with soft tissue necrosis and risk of teeth exfoliation, in the advanced stage.
      Gingival tartar was also found. A significant statistical difference was
      demonstrated between the two examined populations. HIV-related periodontitis may
      represent one of the various features of the clinical picture of HIV infection,
      which must not be underestimated and mistaken for "conventional" adult
      periodontitis. If the diagnosis of periodontic disease is essentially clinic,
      radiography remains nevertheless important, because it yields data on bone
      status, integrity of lamina dura and morphology of roots, which data help make
      diagnosis and prognosis more reliable.

PMID- 9036447
TI  - [Ultrasonography-detected ductal thickness as potential characteristic of breast
      carcinoma].
AB  - We described in former papers the anatomy of the ductal tree, its changes during
      ductal ectasia, periductal fibrosis and the onset of epithelial hyperplasia
      during pregnancy. The present work was aimed at assessing, between the US
      patterns of ductal enlargement, a ductal pattern indicating breast cancer. 392
      women were examined with mammography and real-time US: breast cancer was
      demonstrated in 34 of them. The patients were operated on and their carcinomas
      confirmed at histology. US was performed with radial scans, to depict the ductal
      system from nipple to gland periphery. Three measurements were made at midsize
      subsegmental ducts and the mathematical mean was calculated. Ductal thickness
      ranged 0 to 1.5 mm in 320 healthy women and 2-3 mm in 29 breast cancer patients.
      2 mm was considered as the reference value and the following variables were
      calculated: specificity (90%), sensitivity (85%), positive (43%) and negative
      (98%) predictive value, and overall accuracy (98%). Then, all these variables
      were calculated again excluding 54 women with ductal ectasia and the results
      follow: specificity (89%), sensitivity (84%), positive (42%) and negative (98%)
      predictive values and overall accuracy (98%). The results appear encouraging,
      especially relative to the negative predictive value and overall accuracy of this
      method.

PMID- 9036448
TI  - [Blunt trauma of the larynx: comparative assessment of computerized tomography,
      conventional radiology, and laryngoscopy].
AB  - We report on the retrospective analysis of a series of 11 patients with blunt
      laryngeal injuries examined with Computed Tomography (CT), conventional radiology
      and laryngoscopy, to compare the diagnostic yield of each technique. Conventional
      frontal and lateral radiographs showed subcutaneous emphysema in 5 patients, with
      soft tissue swelling in 4, and thus failed to assess the degree of damage
      adequately. Cross-section CT showed cartilaginous injuries in 5 patients and
      adjacent soft tissue changes in 9, thus allowing rapid and accurate assessment of
      airway damage even in emergency. Laryngoscopy showed laryngeal mucosal tears in 3
      patients, with decreased motion of the left true vocal cord in one patient and of
      both true vocal cords in another, associated with the upward dislocation of
      arytenoid cartilage. Moreover, laryngoscopy showed a mucosal tear in the
      hypopharynx in one patient. Comparative CT and laryngoscopy assessment showed, in
      two cases, that CT can demonstrate even minimal peripharyngeal and perilaryngeal
      air images which are suggestive of posttraumatic mucosal tears. Thus, CT appears
      the most valuable diagnostic tool to study the injured larynx.

PMID- 9036449
TI  - [Role of computerized tomography following transrectal air insufflation and
      hypotonization and transrectal ultrasonography in the staging of rectal tumors].
AB  - Computed Tomography (CT) with rectal air inflation was compared with transrectal
      ultrasound (TRUS) in the preoperative staging of lower rectal cancer in 126
      patients. Precontrast and postcontrast CT scans were performed with 5 mm thick
      slices; the rectum was previously inflated with air and antiperistaltic agents
      were administered. Preoperative results were compared with histologic findings.
      The accuracy, sensitivity and specificity of CT in predicting perirectal spread
      were 76%, 62% and 83%, whereas the corresponding figures for TRUS were 84%, 69%
      and 92%. The accuracy, sensitivity and specificity of CT and TRUS for nodal
      involvement were 58%, 60%, 57% and 72%, 68% and 66%, respectively. These results
      show that TRUS predicts perirectal spread and detects nodal metastases better
      than CT. However CT, when performed appropriately, shows tumor spread into
      perirectal fat and locoregional lymph nodes with high accuracy. Lymphatic
      involvement is strictly correlated with tumor size: TRUS and CT correctly staged
      only 57% and 43%, respectively, of the cases with nodal metastases and max.
      diameter of 5 mm. TRUS sometimes overstaged perirectal tumor growth (13 patients
      in our series) due to perirectal inflammation (9 cases) or artifacts caused by
      the presence of air bubbles between the probe and the tumor surface (4 patients).
      TRUS is a very useful tool for detecting tumor distance from the anal opening; in
      our series, the distance was incorrectly calculated only in one case (3 cm with
      TRUS versus 4 cm at surgery).

PMID- 9036450
TI  - [Computerized tomography in the study of acute sigmoid diverticulosis].
AB  - PURPOSE: To report our experience in the study of acute left-sided colonic
      diverticulitis and to investigate the semiology and the possible diagnostic role
      of Computed Tomography (CT). MATERIAL AND METHODS: In the last 5 years, we
      examined with CT 52 patients with acute sigmoid diverticulitis. The examinations
      were performed with contiguous slices from the diaphragm to the perineum. An
      iodized contrast agent was administered orally in 32 cases and intravenously in
      38. The diagnostic parameters we considered were: diverticula, pericolonic
      inflammation, thickening, intraparietal tracts, fistulas, pelvic phlegmons or
      abscesses, extrapelvic abscess or peritonitis, perforation, colonic obstruction,
      giant diverticula. Moreover, the cases were classified according to the system
      proposed by Neff in 5 stages. RESULTS: In order of frequency, the CT findings
      included: pericolonic inflammatory infiltration (96% of the cases), parietal
      thickening (90.5%), diverticula (88.5%), pericolonic and intrapelvic abscessual
      collections (38.5% each), pericolonic phlegmon and colonic performation (11.5%
      each), extramural fistula (9.5%), stenosis with colonic obstruction (6%),
      intramural tract and extrapelvic abscess (4% each), giant diverticulum (2%). As
      for the severity of the inflammatory involvement, 15% of the cases were included
      in stage 0, 29% in I, 42.5% in II, 13.5% in III, and none in IV. CONCLUSIONS: CT
      is an accurate diagnostic tool in the analysis of acute diverticulitis. Its main
      limitations are relative to the detection of early phases and the differentiation
      from carcinoma. CT should be performed to examine selected patients, with
      complicated diverticulitis.

PMID- 9036451
TI  - [Liver metastasis from carcinoid: diagnostic imaging].
AB  - Our study was aimed at describing the diagnostic imaging patterns of carcinoid
      liver metastases. Six patients with liver metastases secondary to carcinoid tumor
      were examined. The metastases were histologically proved in each patient. All
      patients were examined with ultrasonography (US), Computed Tomography (CT),
      Magnetic Resonance Imaging (MRI) and Digital Subtraction Angiography (DSA). All
      patients were treated with transcatheter embolization of liver metastases.
      Diagnostic imaging methods showed ten to many dozen metastases in each patient.
      Tumor size ranged 0.5 to 14 cm. US showed hypoechoic, hyperechoic and isoechoic
      carcinoid liver metastases with a hypoechoic halo. Large lesions had anechoic
      central areas due to colliquative necrosis. Hypoechoic patterns were the most
      frequent ones. Precontrast CT showed hypodense metastases; very small lesions
      were isodense relative to surrounding liver. CT during contrast agent injection
      showed that the metastases were hyperdense in the arterial phase; contrast
      enhancement was poorer in the portal phase. Large lesions showed a hypodense
      central area due to necrosis which remained hypodense in the late phase. The
      metastases were hypointense on T1-weighted and hyperintense on T2-weighted MR
      images. Gradient echo dynamic imaging with Gd-DTPA showed high-signal metastases
      in the arterial phase and lower signal intensity in the portal phase. DSA, an
      essential exam before embolization, showed tortuous and elongated intra- and
      extrahepatic arteries and tumor neovascularization with no malignant
      abnormalities. In the capillary phase, tumor uptake and inhomogeneous
      hypervascular patterns were shown. Portal veins were only displaced and
      compressed, but never infiltrated by the metastases. All the techniques we used
      contributed to assess liver involvement by carcinoid metastases. DSA must be used
      only before treatment; both CT and MRI showed the hypervascular patterns of the
      metastases, but no technique could predict their nature.

PMID- 9036452
TI  - [Usefulness of the new sequences of magnetic resonance in the study of hepatic
      hydatidosis].
AB  - We investigated the role of new MR Imaging techniques for the diagnosis,
      characterization and staging of hepatic hydatid disease. We examined 21 patients
      (30 hydatid cysts), 7 men and 14 women, ranging in age 26 to 74 years, with known
      hydatid disease. MR examinations were carried out on a 0.5T superconductive
      magnet (Philips Gyroscan T5, Philips Medical System) with the following imaging
      protocol: T1w (TR/TE/NEX: 300/10/4) SE, T2w (TR/TE/NEX: 3000/120/6) TSE and fat
      suppressed (SPIR technique) T2w (TR/TE/NEX: 3000/120/6) sequences. MR Angiography
      examinations were performed with 2D Time of Flight sequences (TR = 33 ms; TE =
      6.9 ms; flip angle = 60 degrees; slice thickness = 4.0 mm with 2.0 mm
      overlapping; matrix = 256 x 256; number of slices = 45-50; acquisition time = 4
      min 19 s), while MR cholangiography was performed with 3D, fat suppressed (SPIR)
      Turbo Spin-echo (TSE) sequences (TR = 3000 ms, TE = 700 ms, ETL = 12, acq. time =
      5 min 48 s). MRI correctly detected all the hydatid cysts on both T1- and T2
      weighted images. Characterization was correct in all the cysts larger than 3 cm,
      where typical signs consistent with hydatid disease were detected. MRA images
      always showed the inferior vena cava and the splenoportal system. The portal
      vessels were demonstrated only up to the first branches. In 3 cases an extrinsic
      compression of the inferior vena cava was diagnosed. MRC, performed in 7 cases,
      showed normal main bile duct caliber in 6 cases, while in another case, where a
      cyst ruptured inside the bile ducts, the communication between the cyst and the
      bile ducts was clearly demonstrated. In conclusion, MR Imaging is a valuable tool
      in the study of liver hydatid disease. Moreover, the availability of such new MR
      techniques as MRC and MRA, greatly improves the diagnostic role of MR imaging,
      especially when studying complications and before surgery.

PMID- 9036453
TI  - [Ultrasonography in the preoperative assessment of candidates for laparoscopic
      cholecystectomy: examination technique and results].
AB  - Laparoscopic cholecystectomy needs a more specific preoperative diagnostic
      approach than open cholecytsectomy. We investigated the role of US in the
      preoperative assessment of patients candidate to laparoscopic cholecystectomy.
      Two hundred patients were examined and then submitted to laparoscopic
      cholecystectomy regardless of US results: the surgical approach had to be changed
      from laparoscopy to laparotomy only in 10 of them. We focused our study on two
      major parameters to reduce the surgical risk: the anatomical study of the so
      called "Calot's triangle" (the hepatic artery, common duct and cystic duct) and
      the study of the gallbladder bed and of pericystic structures. In the study of
      gallbladder walls and bed, US had high sensitivity (100%) and diagnosed no false
      negatives and 11 false positives of pericholecystitis (94.5% specificity), with a
      trend toward overstaging; in these 11 cases, gallbladder wall thickening was seen
      but the organ was not particularly difficult to remove at surgery. In cystic duct
      studies, we correctly diagnosed 6 abnormalities (3 cystic duct stones, 2
      anatomical variants and 1 anatomical variant plus stone), with no false-positive
      and 2 false-negative diagnoses of abnormal insertion (75% sensitivity and 100%
      specificity). The common duct was shown along its whole course in 80% of cases;
      both sensitivity and specificity were 100% in dilatation detection, while the
      presence of stones was diagnosed with 70% sensitivity and 100% specificity.

PMID- 9036454
TI  - [Interactive atlas with magnetic resonance on CD-ROM for Macintosh].
AB  - Computer assisted education in radiology has been increasingly used during the
      past ten years and now complements traditional learning resources. Magnetic
      Resonance Imaging (MRI) of musculoskeletal anatomy, and particularly of joints,
      lends itself naturally to learning modules on computer. This paper describes the
      design, development and use of an interactive computer assisted teaching module
      of MR joint anatomy on CD-ROM for Macintosh: to date, we have used this atlas for
      ankle and elbow anatomy. The atlas is divided into three main sections: MR
      anatomy, traditional anatomy and a quiz. On each MR image, any anatomical detail
      can be identified clicking on it with the mouse. Buttons allow to visualize cross
      reference points and to go directly on the desired image. If the student wants to
      look at anatomical drawings of the last identified structure, a button retrieves
      all the cards in the traditional anatomy section containing that structure.
      Finally, the student can make his own self-assessment, verifying his learning
      immediately with the exam mode: the software makes a random selection of 10 MR
      images where an anatomical structure must be indicated: if the answer is wrong,
      the software gives the right one and shows the misinterpreted structure. Then,
      the student is given a total score for his performance. The computer assisted
      teaching modules present some advantages: the images can be viewed in a given
      sequence (like traditional learning resources) or in any self-paced, customized
      way; this possibility, together with the friendly interface of Macintosh
      computers could make learning more active and pleasant.

PMID- 9036455
TI  - [Emergency ultrasonography].
AB  - We reviewed the emergency US exams carried out in the Radiology Department of the
      Sesto S. Giovanni Hospital on patients referred from the First Aid, Surgery and
      Medicine Depts in 1994. 202 of 8,400 US exams (2.7%) were emergencies in patients
      of both sexes aged 15 to 83 years. The exams were carried out in the daytime by 4
      radiologists with different (longer/shorter) experience. The results were
      arranged in tables showing the referring department, the number of exams
      according to the anatomical district, the number of negative exams (122 cases)
      and of the exams where the clinical suspicion was confirmed (80 cases), as well
      as the frequency of the different conditions diagnosed. The conditions usually
      involved the abdominal organs and particularly the bile ducts (48 cases), showing
      gallstones which were quickly operated on. Renal colics were the second most
      frequent finding (10 cases). The results of many precautionary exams were poorly
      significant. Considering the numerous indications of emergency US, currently
      including also acute appendicitis and soft periskeletal tissue traumas, we
      conclude that more operators and technically adequate equipment are needed.

PMID- 9036456
TI  - [Hodgkin's lymphoma: problems in the treatment of the early stages].
AB  - The prognosis for Hodgkin's disease patients has improved markedly in the past 3
      decades, thanks to improved staging techniques and therapeutic advances in both
      radiation and chemotherapy. Yet, individual treatment schedules continue to
      evolve: in particular, the extent of irradiation fields, the allocation of
      Hodgkin's patients to prognostic groups using information from clinical staging
      techniques and the choice of radiotherapy alone versus combined modalities are
      still controversial in the early stages of this disease. To try to eliminate the
      need for staging laparotomy, the EORTC investigated the role of clinical staging
      in different studies and found that favorable clinical stage I/II patients do not
      need laparotomy and that irradiation alone yields satisfactory results. Current
      treatment goals include maximizing the cure rate while minimizing toxicity, late
      side-effects in particular. An approach is to reduce irradiation fields and
      combine irradiation with chemotherapy. There is no doubt that various organ sites
      can be cumulatively damaged by this combined approach, but new protocols seem to
      yield better results. Several literature findings are reviewed in this paper. The
      allocation of stage IA and IIA Hodgkin's disease patients to prognostic groups
      using information from clinical staging procedures appears to be a very important
      step. The combined approach seems to be useful in patients at intermediate risk
      of relapse. We conclude that excellent results and very little toxicity and
      morbidity can be achieved through respect and collaboration between the
      chemotherapist and the radiotherapist.

PMID- 9036457
TI  - [Assessment with magnetic resonance imaging of response to radiotherapy for
      tongue and mouth floor tumors].
AB  - To investigate the role of Magnetic Resonance Imaging (MRI) in assessing the
      effects of radiation therapy and in differentiating postirradiation scar tissue
      from residual tumor, we examined 22 patients with primary squamous cell carcinoma
      of the tongue and floor of the mouth treated with definitive radiation therapy;
      all patients were examined before and after treatment. Pretreatment MRI showed
      mass effect and obliteration of the fascial planes, with hyperintense signal on
      T2 and T1 post-Gd-DTPA injection sequences in all patients. Follow-up exams were
      performed 4 months after radiation therapy completion to wait for postirradiation
      phlogistic changes to become less apparent. The role of posttreatment exams was
      determined on the basis of clinical and bioptic follow-up. Radiation therapy
      yielded complete remission in 16/22 patients and partial remission in 6/22. MR
      follow-up showed, in complete remission patients, persistently obliterated
      fascial planes in 12/16 patients (75%) and a residual mass, hypointense on T2
      weighted sequences and without enhancement in 9/16 patients (56%). In all partial
      remission patients, MRI showed some residual tissue hyperintense on T2-weighted
      sequences, with persistent enhancement. Persistent alterations in primary tumor
      sites, such as residual tissue and fascial plane obliteration, are frequent
      findings after irradiation. Hyperintense signal and enhancement can persist for
      months after radiation therapy as signs of postirradiation changes. To conclude,
      MRI performed 4 months after radiation therapy appears as a reliable tool to
      refer a residual mass to scar tissue when MR signal is hypointense on T2-weighted
      and enhanced sequences and to residual tumor when MR signal is hyperintense on T2
      weighted and post-Gd-DTPA sequences.

PMID- 9036458
TI  - [Role of computerized tomography in bladder carcinoma treated with simultaneous
      combined radiotherapy and chemotherapy].
AB  - We report on the pneumocystography-CT follow-up of locally aggressive bladder
      carcinoma patients treated with combined and simultaneous irradiation and
      chemotherapy. Particular attention was paid to assess residual thickening of the
      wall involved by the tumor, which is the most critical parameter to discriminate
      a persistent from a resolved condition. We examined 16 patients (mean age: 66.5
      years) with histologically locally advanced urinary bladder cancer staged T2-T3.
      All patients underwent the first CT exam of the bladder with the
      pneumocystography technique before therapy, for disease staging, another exam
      after chemotherapy and a third one after simultaneous irradiation and
      chemotherapy. The endoluminal mass completely regressed in all cases, with normal
      endoscopic findings. In 9 of 16 cases, the bladder wall was thickened in the
      tumor site, with normal mucosal surface. The histology of bioptic specimens
      obtained during cystoscopy showed a high frequency of phlogistic reactions from
      foreign bodies, corresponding to the bladder wall thickening seen on CT images.
      We conclude that, in extensive neoplastic bladder wall involvement, therapy
      induced histologic regressive phenomena can cause a granulomatous reaction in the
      bladder wall, thus thickening it, which is the most frequent sign in these cases
      but that, in our experience, was never associated with tumor invasion. This
      should be always considered in the CT studies performed after this kind of
      combined treatment.

PMID- 9036459
TI  - [Radiotherapy of the breast: changes in the volume of the lung covered in the
      treatment fields and resulting changes in dose distribution].
AB  - In breast cancer adjuvant therapy, respiratory movements continuously modify the
      irradiated volumes and the anatomical shape of this body region. Fifteen patients
      were submitted to 3 Computed Tomography (CT) sequences for treatment planning:
      the first one without any indications to the patient (the standard sequence) and
      the second and the third one with spontaneous stopped inspiration and expiration,
      respectively; the patient was always in the same position. The treatment was
      planned on standard CT images and then applied to the other sequences,
      maintaining all parameters unvaried, including isocenter position and treatment
      time. The lung volumes within the fields (and those included in the 95%, 100%,
      105% isodoses referred to the prescribed dose) were evaluated with dose/volume
      histograms. The average irradiated lung was 69 cm3 (DS 28) in standard sequences,
      136 cm3 (DS 67) in inspiration and 41 cm3 (DS 25) in expiration. The pulmonary
      volume within the above isodoses exhibited similar changes. In other words, the
      lung volume actually irradiated during the whole treatment is smaller than the
      one which can be calculated on standard CT sequences and it corresponds to
      expiration volume. The remaining part falls into a wide "twilight zone" relative
      to dose. Therefore, the true risk of lung toxicity can be similarly lower than
      the calculable one on standard CT images. Thus, the complication risk (based on
      dose/volume histograms and normal tissue control probability parameters) could be
      assessed in new prospective studies, introducing a corrective factor for the
      irradiated lung volume, because the latter is smaller than that shown by standard
      CT.

PMID- 9036460
TI  - [Diagnostic pitfalls of magnetic resonance of the knee: an unusual case of
      meniscal dislocation].

PMID- 9036461
TI  - [Special usefulness of ultrasonography in a case of multiple foreign bodies in
      soft tissues].

PMID- 9036462
TI  - [A case of tracheal rupture caused by blunt trauma associated with
      pneumoretroperitoneum and intraspinal gas].

PMID- 9036463
TI  - [Features of pulmonary strongyloidiasis with radiology and computerized
      tomography. Report of a case].

PMID- 9036464
TI  - [Lung cancer with bullous cystic onset. A case report].

PMID- 9036465
TI  - [The computerized tomography halo sign in a case of productive granulomatous
      pulmonary tuberculosis without intra and/or extralesional hemorrhage].

PMID- 9036466
TI  - [Inflammatory mediastinal pseudotumor. Report of a case].

PMID- 9036467
TI  - [Subcutaneous emphysema, pneumomediastinum, and pneumoretroperitoneum caused by
      perforation of sigmoid diverticulum. Report of a case studied with spiral
      computerized tomography].

PMID- 9036468
TI  - [Acute complicated appendicitis: report of a case diagnosed with computerized
      tomography].

PMID- 9036469
TI  - [A case of splenosis. Assessment with imaging methods].

PMID- 9036470
TI  - [Spontaneous retroperitoneal hemorrhage from renal angiomyolipoma. Report of 2
      cases].

PMID- 9036471
TI  - [Use of the Cragg stent in the treatment of popliteal artery aneurysm: report of
      a case].

PMID- 9036472
TI  - [Implantable automatic defibrillator after MADIT and EMIAT].

PMID- 9036473
TI  - [Registry of activities at the Section of Hemodynamics and Interventional
      Cardiology in 1995].
AB  - The results of the Spanish Registry of Hemodynamic and Interventional Cardiology
      are presented. Eighty hospitals have collaborated, which represent 100% of the
      cardiac catheterization laboratories. Seventy-two of which performed cardiac
      catheterization in adults and eight laboratories which exclusively performed
      pediatric cardiac catheterizations. We have studied 57,773 diagnostic procedures
      which were performed, which represents an increase of 11% from 1994. In addition,
      12,359 angioplasties were performed, representing an increase of 18%. This
      represents 312 PTCAs per million people. PTCA success (91%) and global
      complications (3.2%) were similar to those of 1994. There was an increase in
      stent implantation: 3,418 procedures with 4,321 stents. This represents 1.26
      stent per procedure. Sixty-four per cent of them were done electively and with a
      marked reduction in complications rate: subacute thrombosis, 1.6%, MI, 1.8% and a
      mortality of 1.1%. The number of mitral valvuloplasties decreases 16% and the
      pediatric interventional procedures (464) were similar to those of last year.

PMID- 9036474
TI  - [Long-term clinical course of acute myocarditis. Prospective study of a series of
      99 patients (1987-1995)].
AB  - BACKGROUND: The natural history of acute myocarditis is not well known. The aim
      of our study was to assess the spontaneous outcome of patients with this disease
      and its possible relation with progression to chronic dilated cardiomyopathy.
      METHODS: With this aim, we have carried out a prospective study of 99 patients
      consecutively diagnosed with acute myocarditis in our hospital from 1987 to April
      1995, with a mean follow-up of 34 +/- 25 months. Acute myocarditis was diagnosed
      by clinical, echocardiographic and isotopic (detection of myocite damage) data,
      in absence of any other cardiac lesion. RESULTS: Mean age was 26 +/- 17 years;
      70% of the patients were male. Initial symptoms were dyspnea in 58% of the
      patients, chest pain in 33% and arrhythmias in 9%. Severe heart failure was
      present in 62% of the patients, ventricular arrhythmias in 16% and
      supraventricular arrhythmias in 16%. Cardiothoracic index was 0.50 +/- 0.07. Left
      ventricular ejection fraction was 0.40 +/- 0.18, although in 44% of the patients
      it was lower than 0.30. Immunosuppressive therapy was not used in any case.
      Outcome was favorable in 70% of the patients, who had a normal ejection fraction,
      while 13% died or needed heart transplantation during follow-up and 17%
      progressed to stable chronic dilated cardiomyopathy. Final ejection fraction was
      0.53 +/- 0.17, significantly higher than the initial, 0.40 +/- 0.18 (p < 0.05);
      this improvement in ejection fraction was mainly observed during the first month
      after diagnosis (0.49 +/- 0.18). The proportion of patients with an ejection
      fraction of less than 0.30 decreased from 44% to 21% at the end of follow-up.
      CONCLUSIONS: Spontaneous outcome of acute myocarditis is good in the majority of
      patients, although an unfavourable evolution was observed in almost 30% of the
      patients (death, need of heart transplantation or chronic dilated
      cardiomyopathy). Improvement in ventricular function mainly occurs at short-term,
      during the first month of evolution in our study.

PMID- 9036475
TI  - [Sudden death in heart failure].
AB  - INTRODUCTION: Our study was designed with the primary objective of evaluating the
      cardiac, overall and sudden mortality in patients with class IV heart failure
      (NYHA) managed with standard treatment and captopril (50 mg/8 hr. max.). MATERIAL
      AND METHODS: 95 consecutive patients were enrolled in 21 hospitals and were
      followed for 6 months in order to design an interventional clinical trial to
      reduce sudden death. RESULTS: Death occurred in 14 patients (14.7%; i.c. 8.3% -
      23.5%; p < 0.05). There were no non-cardiovascular deaths in the group. There
      were 6 sudden death cases (42.9%; i.c. 16.9% - 68.8%, p < 0.05). Patients who
      died had a higher baseline end-diastolic (p < 0.05) and end-systolic (p < 0.01)
      diameter of the left ventricle (LV) and lower values of systolic (p < 0.01) and
      diastolic (p < 0.05) blood pressure. During the follow-up phase, heart rate,
      ventricular premature contraction, blood pressure and LV diameters decreased
      significantly in the whole group (p < 0.05, p < 0.001). We found no any
      differences during the follow-up phase between the patients who died and those
      who survived. In the patients who died we found no any differences between sudden
      death cases and the other death cases. CONCLUSIONS: Sudden death was less
      frequent than we had expected and due to this fact it is impossible for us to
      design an interventional trial.

PMID- 9036476
TI  - [Cardiac myxoma. Anatomo-clinical and immunohistochemical study of 13 cases].
AB  - INTRODUCTION: Cardiac myxomas are the most frequent benign heart tumors, and have
      an uncertain histogenesis. An endothelial, subendocardial and an undifferentiated
      mesenchymal cell origin with vasoformative characteristics has been suggested.
      The aim of this study was to make a review the cardiac myxomas at our institution
      paying special attention to its histogenesis. MATERIAL AND METHODS: We reviewed
      the clinico-pathological features of the 13 cardiac myxomas studied at our
      hospital, and we stained them with immunohistochemical stains. RESULTS: The
      average age on presentation was 62.8 years. 12 cases were left atrial, one of
      them with cerebral metastasis. The average size was 6.3 cm. Microscopically all
      of them were composed of a myxoid-matrix with spindled cells and small neoformed
      vessels. The tumors were completely positive for Vimentin and randomly positive
      with Actin and VIII-RA. CAM 5.2 was strictly negative. CONCLUSION: These results
      show that these kinds of tumors are neoplasms arising from mesenchymal
      pluripotential cells which are capable of many types of differentiation
      (endothelium, etc).

PMID- 9036477
TI  - [Echocardiography with dobutamine in hypertensive patients with chest pain].
AB  - INTRODUCTION: The exercise stress test shows limited diagnostic accuracy for the
      detection of coronary artery disease in hypertensive patients. Echocardiography
      with dobutamine is a useful tool in the assessment of coronary artery disease.
      PURPOSE: Our purpose has been to compare dobutamine stress echocardiography and
      exercise stress test for diagnosing coronary disease in hypertensive patients.
      MATERIAL AND METHODS: Dobutamine stress echocardiography (administered up to 40
      micrograms/kg/min, and atropine when necessary), exercise stress test and
      coronary arteriography were performed on 74 hypertensive patients with chest pain
      and no previous history of coronary artery disease. RESULTS: Forty-eight (65%)
      patients underwent a diagnostic exercise stress test and 66 (89%) a diagnostic
      dobutamine stress echocardiography. Coronary artery disease (> or = 70% stenosis
      in, at least, one major vessel) was demonstrated in 28 (58%) patients who
      underwent a diagnostic exercise stress test, and in 39 (59%) patients who
      completed a dobutamine stress echocardiography. Sensitivity for exercise stress
      test was 82%, and 79% for dobutamine stress echocardiography (p = NS).
      Specificity was higher for dobutamine stress echocardiography (100% vs 60%; p <
      0.005). CONCLUSIONS: Dobutamine stress echocardiography has high sensitivity and
      specificity for the detection of coronary artery disease in hypertensive
      patients. Dobutamine stress echocardiography has higher feasibility and
      specificity than exercise stress test in this group of patients.

PMID- 9036478
TI  - [Heart rehabilitation. Cost-effectiveness analysis].
AB  - OBJECTIVE: Heart rehabilitation programmes improve the quality of life of
      coronary patients and the prognosis of the illness. Implementing these
      therapeutic systems into practice would be easier if their economic efficiency
      was proven. MATERIAL AND METHODS: The expenses created by 180 survivors of a
      myocardial infarction have been studied at the first and sixth year after the
      acute episode. The survivors were divided, at random, into two groups of 90. One
      of them (RG) underwent a rehabilitation programme (physical training,
      psychological action and control guidelines of risk factors). The other (CG)
      served as a control. RESULTS: The profits, analyzing the direct expenses
      (readmissions to hospital) were of 5,074,039 ptas. the first year (CG:
      19,901,578; RG: 14,827,539), and of 17,451,910 ptas. at the end of the study (CG:
      54,370,249; RG: 36,918,339). Better results were obtained when reviewing the
      indirect expenses (derived from return to work), since the profits were of
      26,000,000 ptas. after the first year (CG: 54,750,000; RG: 28,750,000) and of
      209,750,000 at the sixth year (CG: 438,000,000; RG: 228,250,000). The saving per
      patient was of 272,437 ptas. during the first 12 months and of 2,415,220 at the
      end of the follow-up. CONCLUSIONS: These results justify the fact that the Public
      Administration and private Insurance Providers are taking into account the
      adequacy of implementing these therapeutic systems into practice.

PMID- 9036479
TI  - [Etiopathogenesis and classification of dilated cardiomyopathy].
AB  - Dilated cardiomyopathy is a diffuse disease of the myocardium, with systolic
      dysfunction and ventricular enlargement which is clinically expressed as heart
      failure and sudden death. A variety of etiologies, including myocardial diseases
      produced by specific local or systemic disorders can cause this syndrome. The
      etiological diagnosis is very difficult in the clinical setting. Because the
      progression of the disease is potentially reversible, discovering the cause, if
      possible, seems very interesting. The basic pathogenic mechanisms are not well
      known. The different etiopathogenic hypotheses, viral, immunological, genetic,
      and toxic are not incompatible and may even be complementary. Research through
      immunogenetical and molecular biology techniques is the key to understanding the
      basic mechanisms. The usefulness of genetic therapy is under investigation.

PMID- 9036480
TI  - [Transient atrioventricular conduction 1:1 in a patient with common atrial
      flutter following the administration of adenosine triphosphate].
AB  - A patient with atrial flutter and 2:1 atrioventricular conduction and
      acceleration to 1:1 conduction after administration of a single i.v. dose of 10
      mg adenosin triphosphate (ATP) is presented. Despite the fact that ATP is a very
      useful drug for the treatment of paroxysmal supraventricular tachycardia. Its use
      as a diagnostic tool in atrial flutter must be carefully considered and the
      possibility of transient acceleration of AV conduction must be taken into
      account.

PMID- 9036481
TI  - [Reversible dilated cardiomyopathy and hyperthyroidism].
AB  - Thyrotoxicosis may precipitate atrial fibrillation, myocardial ischemia or heart
      failure if underlying heart disease is present. However, reversible dilated
      cardiomyopathy is rare. We report a case of a 51-year-old man with thyrotoxicosis
      and dilated cardiomyopathy that was reversed with antithyroid treatment.

PMID- 9036482
TI  - [Early thrombosis of aortic porcine bioprosthesis].
AB  - A case of thrombosis on an aortic bioprosthesis after the fourth month of
      implantation is presented. The patient had been well anticoagulated for the first
      three months after surgery. A suspicious diagnosis was made when the patient
      started with symptoms of cardiac failure and angina and an Echo-Doppler showed a
      significant transvalvular gradient. The definitive diagnosis will be determined
      with the removal of the valve at surgery. Although this is a rarity as an early
      complication, it should be kept in mind in such cases. Surgical intervention is
      mandatory and life-saving.

PMID- 9036483
TI  - [Extracorporeal circulation in pregnancy: report of a case. Update and review of
      the literature].
AB  - Parameters of flow, temperature and perfusion, and modifications in body fluids
      secondary to surgery with extracorporeal circulation do not imply an increase in
      maternal risk during pregnancy but they eventually considerably increase fetal
      morbimortality. We present the case of a 22 week pregnant woman with severe
      aortic stenosis who underwent extracorporeal surgery for valve replacement
      without fetal mortality during the procedure. Literature about the use of
      extracorporeal surgery in the treatment of valve pathology in pregnancy, the
      parameters in which the reduction of fetal morbimortality is based and
      alternative treatments are broadly reviewed.

PMID- 9036484
TI  - [100 years of heart surgery].

PMID- 9036485
TI  - [Cardiovascular surgery in Spain in 1994. Registry of Interventions of the
      Spanish Society of Cardiovascular Surgery (SECCV)].
AB  - The Spanish Society of Cardiovascular Surgery Registry of 1994 includes data from
      44 hospitals. Within this year a total of 25,385 patients were operated on, with
      an average of 577 operations/ center. Fourteen thousand one hundred and fifteen
      of these were cardiac operations under extracorporeal circulation, with an
      average of 320 cases/hospital. The number of coronary surgeries was greater to
      that of valvular procedures (6,660 vs 5,386). The average of coronary
      graft/patient was 2.67. The 67.6% of these were arterial grafts. The hospital
      mortality was 7.8%, 5.9%, 6.6%, 7.0% and 4.1% for 1, 2, 3, 4 and 5 or more
      grafts, respectively. The number of valvular prothesis implanted was 6,243 and
      80.7% of these were mechanical. There were 2,274 (58.2%) patients operated on
      aortic valvular surgery and 1,582 by mitral surgery, with a mortality of 5.9 and
      8.6%, respectively. The number of patients operated on for congenital cardiac
      defects was 1,993 (1,367 open heart surgeries and 626 closed). There were 5,023
      operations by peripheral vascular surgery. The number of aneurysms operated on
      during this year was 506.

PMID- 9036486
TI  - [Should all patients with unstable angina undergo routine coronary angiography?
      Arguments in favor].

PMID- 9036488
TI  - [Usefulness of transesophageal echocardiography in the diagnosis of coronary
      anomalies].
AB  - BACKGROUND: Although rare, anomalous coronary arteries are associated with
      myocardial ischemia and sudden death. Identification is made by angiography but
      its true course is difficult to determine even with this invasive procedure.
      OBJECTIVES: The purpose of this study is to determine the role of transesophageal
      echocardiography (TEE), Doppler and color flow Doppler, in identifying the origin
      and course of anomalous coronary arteries. MATERIAL AND METHODS: Six patients
      with angiographically confirmed anomalous coronary arteries were studied by TEE,
      Doppler and color flow Doppler. RESULTS: The abnormal origin was confirmed in all
      six patients. In three, the left main originated from the right sinus of
      Valsalva. In one the right coronary artery from the left sinus of Valsalva. One
      was a single right coronary artery from the right sinus of Valsalva, and one, had
      a fistula between the coronary artery and the right ventricle. In four, the TEE
      was able to demonstrate clearly the course in relation to the great vessels, two
      were interarterial and one posterior. Color flow Doppler was obtained in four
      patients. In one patient, there was increase in diastolic flow velocity due to
      proximal coronary obstruction. One had increase of the systolic flow velocity.
      CONCLUSIONS: TEE is useful test for diagnosing the origin of anomalous coronary
      arteries and confirming its course in relation to the great vessels. Doppler flow
      Doppler is useful in localization the vessel.

PMID- 9036487
TI  - [Should all patients with unstable angina undergo routine coronary angiography?
      Arguments against].

PMID- 9036489
TI  - [Influence of the degree of aortic valve calcification on the estimate of
      valvular area using planimetry with transesophageal echocardiography].
AB  - BACKGROUND AND PURPOSE: Continuity equation to measure aortic valve area is
      limited by poor acoustic window or difficulty in obtaining acceptable Doppler
      signal. Our aim has been to analyze the accuracy of planimetry by transesophageal
      echocardiography to calculate aortic valve area and the impact of calcification
      on results. METHODS: Planimetry of aortic valve area by transesophageal
      echocardiography has been compared to continuity equation by transthoracic
      approach and the Gorlin formula in 26 consecutive patients with aortic stenosis.
      Degree of calcification was qualitatively estimated by the 3 methods and 2 groups
      were distinguished: group A (mild or moderate calcification) and group B (severe
      calcification). RESULTS: An excellent agreement between continuity equation and
      the Gorlin formula was found (mean difference: 0.03 +/- 0.15 cm2). Agreement
      between transesophageal planimetry and the Gorlin formula was poor (mean
      difference: 0.14 +/- 0.25 cm2). Planimetry and the Gorlin formula demonstrated an
      excellent agreement in group A (mean difference: -0.03 +/- 0.17 cm2). By
      contrast, agreement in group B was not acceptable (mean difference: 0.27 +/- 0.22
      cm2). CONCLUSIONS: 1) continuity equation by transthoracic echocardiography is
      useful in calculating aortic valve area. 2) aortic planimetry by transesophageal
      echocardiography is an excellent method in noncalcified aortic valves, and must
      not be used on severely calcified valves.

PMID- 9036490
TI  - [Increase of myocardial perfusion during antilipemic treatment in patients with
      ischemic cardiopathy].
AB  - OBJECTIVES: To evaluate if cholesterol lowering therapy with simvastatin
      increases myocardial perfusion, assessed by Thallium-201 single photon emission
      computed tomography (SPECT) after dipyridamole, in patients with coronary artery
      disease. PATIENTS AND METHODS: Ten hypercholesterolemic subjects with coronary
      artery disease were selected for a pilot study. Lipid and lipoprotein analysis
      and Thallium-201 SPECT were performed before and after 16 weeks of treatment with
      40 mg of simvastatin QD. SPECT images were qualitatively analyzed in 8 myocardial
      segments using a 4 point scoring system. Quantitative evaluation was performed in
      13 segments. The myocardial region with the maximal mean counts per pixel on the
      stress study was considered the reference region. TI201 activity in all other
      myocardial regions was expressed as a percentage of the activity in the reference
      region. RESULTS: Total cholesterol and LDL cholesterol were reduced by 28.4% and
      37.1% with treatment. Global myocardial perfusion was increased in all patients.
      Qualitative analysis demonstrated that cholesterol lowering improved myocardial
      perfusion during dipyridamole stress. Quantitative analysis showed an increased
      global perfusion during stress (41.8% vs 54.6%; p < 0.0001), due to increased
      perfusion of previous ischemic segments (32.4% vs 49.4%; p < 0.0001) but without
      changes in previous normally perfused segments (71.5% vs 71.3%). CONCLUSION:
      Reduction of cholesterol levels in hypercholesterolemic subjects with coronary
      artery disease increases myocardial perfusion in ischemic segments during
      dipyridamole stress test as assessed by single photon emission computed
      tomography (SPECT).

PMID- 9036491
TI  - [Coronary perfusion: classification based on the type and relative extension of
      coronary irrigation. Morphologic determinants].
AB  - INTRODUCTION AND OBJECTIVES: This work attempts to systematize the arterial
      segmentary distribution of the left ventricle and confirm the existence of
      coronary irrigation patterns, and determine the principals for the clinical
      application for diagnosis or therapeutics, using as the starting point,
      Selvester's classification of the arterial irrigation of the left ventricle.
      METHODS: Ninety human heart specimens from autopsies were studied. The average
      age of the sample was 61.09 +/- 21.96 years. The range was between 4 days and 94
      years old. The coronary artery tree was dissected, and each artery responsible
      for the irrigation of each of the twelve left ventricle segments was identified.
      The percentage of the muscular mass, of each segment in which the left ventricle
      had been divided, irrigated by each coronary artery, was obtained. RESULTS: The
      analysis of the 12 segments of the left ventricle show that the three septal
      segments (basal, mesial and apical) present a type of irrigation which is
      practically constant and of a shared type. The superoapical, posterobasal and
      posteromesial segments present an irrigation with a high index of exclusivity for
      the anterior interventricular and circumflex arteries. In the rest of the
      segments the vascularization is of a mixed type, although the apical segments
      reach an important degree of arterial exclusivity. CONCLUSIONS: The relative
      number of ventricular segments, exclusively irrigated by the interventricular and
      circumflex arteries, makes it possible to describe three groups of arterial
      irrigation (I, II, III), and each of them, in two subgroups (A, and B) depending
      on the percentage of ventricular segments irrigated in an exclusive or shared
      mode, by the interventricular or circumflex arteries.

PMID- 9036492
TI  - [Myocardiopathies (XIII). Markers of clinical course in patients with dilated
      myocardiopathy].
AB  - The natural history of dilated cardiomyopathy, above all in asymptomatic
      patients, is not easily predictable. Nevertheless, when congestive heart failure
      is present, prognosis is significantly worse. The development of new therapeutic
      methods, both pharmacological (angiotensin converting enzyme inhibitors and other
      drugs) and surgical (heart transplantation), have improved the prognosis of this
      disease. In this article, we review some subjects of interest related to the
      management and treatment of patients with dilated cardiomyopathy that have been
      studied recently: identification of potentially reversible causes, optimization
      of medical therapy, prognostic markers, identification of high-risk patients and
      selection of candidates for heart transplantation.

PMID- 9036493
TI  - [Atypical coarctation. Repair with Dacron graft and aortic sarcoma].
AB  - A patient with a localized severe stenosis of his lower thoracic aorta is
      described. He presented a coarctation like syndrome with hypertension, pulseless
      legs and left ventricular failure. At surgery a biopsy of the lesion and bypass
      graft were performed. Pathology diagnosed intimal hyperplasia. Twenty eight
      months later he developed a sarcoma.

PMID- 9036494
TI  - [Congenital stenosis of pulmonary veins in the adult].
AB  - We report a case of congenital bilateral pulmonary vein stenosis associated with
      a double-chambered right ventricle, ventricular septal defect and persistence of
      the ductus arteriosus in a 29 year-old female. The angiographic,
      echocardiographic and surgical findings are discussed. A precise diagnosis, the
      utility of the echocardiography and the surgical correction of this type of
      ostial stenosis is also reported.

PMID- 9036495
TI  - [Right coronary artery originating from the left sinus of Valsalva. Surgical
      repair].
AB  - Anomalous origin of right coronary artery from left coronary sinus has been
      considered a minor disease without relevance. Currently it is associated with all
      symptoms derived from myocardial ischemia because of its lower coronary reserve.
      We present one patient with anomalous origin of right coronary artery from left
      coronary sinus surgically treated with saphenous vein aorto-coronary bypass.
      Doppler velocimetry shows the improvement of myocardial reserve after surgery.

PMID- 9036497
TI  - [Capsular rupture of N2 resected lymph nodes and surgery of bronchial cancer].

PMID- 9036496
TI  - [Syncope associated with glossopharyngeal neuralgia and parapharyngeal tumor].
AB  - The reflex-induced cardiovascular syncope is rarely associated with facial
      neuralgia and neck neoplasms. We report the case of a male with vasopressor and
      cardioinhibitor syncopes, despite the implantation of a pacemaker. Because of a
      glossopharyngeal neuralgia, a neoplasm of the left parapharyngeal fossae is
      diagnosed. The pathophysiology and the therapeutic approach is discussed.

PMID- 9036498
TI  - [Interaction between tumor necrosis factor-alpha and the smooth muscle cells of
      the airway: implication in the physiopathology of asthma].
AB  - Asthma is a disease characterized by a bronchial hyperresponsiveness (BHR).
      Although the underlying mechanisms that induce this increase in bronchial
      reactivity remain unknown, evidence suggests that the inflammatory process
      present in the airways could play an important role in the development of BHR.
      This latter may result from alterations in the intrinsic properties of airway
      smooth muscle induced by inflammatory mediators. Tumor necrosis factor alpha (TNF
      alpha), a pro-inflammatory cytokine, appears to be an interesting candidate
      considering on one hand that it is able to induce, in human and in animals, a BHR
      to different inhaled pharmacological agents and on the other hand that high
      levels of TNF alpha were found in asthmatic airways. Our studies show that TNF
      alpha induces in a direct manner some modifications of the bronchial smooth
      muscle which can underly an increased muscle contractility. These modifications
      include an alteration of the intracellular calcium homeostasis and an increase in
      the mitogen capacity of the human airway smooth muscle cells. Using antibodies
      directed against the two existing receptor type of TNF alpha (TNFRp55 and
      TNFRp75) and TNF alpha-analogs obtained by directed mutagenesis, we showed that
      these modifications result from the activation of TNFRp55. The implication of
      this receptor in the other pathophysiologic characteristics of asthma is also
      discussed in this review.

PMID- 9036499
TI  - [The epidemiology and genetics of asthma. II. Genetic aspects of the epidemiology
      of asthma and atopy].
AB  - Asthma is regarded as a disease with a complex interaction between genetic and
      environmental factors. Since the end of the 1970s and during the 80s the world
      has seen an increase in the prevalence, morbidity and mortality linked to asthma.
      The rapidity of progress of this phenomenon means that it cannot be explained
      only by modification of genetic factors and stresses the preponderance of
      exogenous factors. The purpose of this review is to examine the epidemiological
      knowledge of these environmental factors and of the genetic factors in asthma in
      order to underline how these genetic and exogenous factors interact and modulate
      the occurrence of the asthmatic disease. In the first part of this general review
      we discussed the epidemiology of asthma in terms of prevalence, incidence,
      mortality, cost and socio-professional and scholastic repercussions and
      underlined for each environmental factor its causal role and/or exacerbation in
      asthma as well as its contribution in the increased prevalence and severity of
      asthma. In the second part of this general view we touch on the epidemiological
      knowledge of the genetics of asthma and of atopy.

PMID- 9036500
TI  - [Cell growth factors and tissue repair].

PMID- 9036501
TI  - [Drug-induced pneumopathies accompanied by acute respiratory insufficiency].
AB  - Drug induced pneumonias accompanying acute respiratory failure are defined by a
      delay in presentation of less two months and severe hypoxaemia (PaO2 < 60 mmHg in
      ambient air). They are poorly indexed, often poorly understood by the clinician
      and pose difficult problems both of diagnosis and treatment. This general review
      touches successively on hypoxaemic drug induced pneumonia observed in oncology
      and haematology then those observed outside this very specific context. In each
      of the two groups five questions are posed: 1) Which patients? 2) Which clinical
      patterns? 3) What initial diagnostic discussion? 4) Which successful elements
      support the drug induced hypothesis? 5) What outcome? The replies obtained were
      compared to case reports from the literature (188 references) or from recent
      general reviews concerned more specifically with the hypoxaemic forms.

PMID- 9036502
TI  - [Chronic obstructive bronchitis in a fodder farming setting].
AB  - Respiratory disease in agricultural workers are dominated both in terms of
      frequency and severity by chronic obstructive long disease. In the Doubs, in
      dairy cereal farmers, the prevalence of chronic bronchitis in active farm workers
      is around 10 per cent, and 6 per cent are non-smokers. It is twice the level of
      the control population of non-exposed subjects. The frequency is most elevated in
      the men and increases both with age and with altitude. A longitudinal study of
      male farm workers aged more than 45 has shown that there is an abnormally rapid
      loss of forced expired volume in one second (FEV1). Two different studies carried
      out in the Doubs have revealed epidemiological, respiratory function and
      immunological arguments in favour of immuno-allergic mechanisms. Notably,
      obstructive chronic bronchitis (OCB) occurs more frequently in agricultural
      workers with a previous history of farmer's lung or previous sub-acute delayed
      symptoms in relation to exposure. On the other hand, there are no close links
      between OCB and the intensity of antigenic exposure (the total quantity of fodder
      handled). By contrast, there is a relationship between exposure to thermophillic
      actinomycetes (antigen of farmer's lung) and OCB. The frequency of serum
      precipitins is most elevated in farm workers with OCB than in asymptomatic
      agricultural workers. Finally, non-smokers who are suffering from OCB without
      evidence of farmer's lung, have a respiratory function profile and also alveolar
      lavage cell pattern characteristic of extrinsic allergic alveolitis after
      provocation tests to mouldy hay. These arguments are in favour of immuno-allergic
      mechanisms in the pathogenesis of chronic bronchitis in farm workers which seems
      to be well differentiated from chronic bronchitis due to smoking.

PMID- 9036503
TI  - [Diagnostic percutaneous thoracic punctures. Assessment through a critical study
      of a compliation of 2406 cases].
AB  - The aim of this retrospective study of 2,406 diagnostic percutaneous thoracic
      needle aspirations under computer tomographic control was to assess the
      diagnostic value of this method, the technical problems and the complications and
      finally, to refine the indications. Percutaneous needle aspiration had been
      carried out after negative fibreoptic bronchoscopy. The authors review their
      technique and show the value of biopsy material which is only slightly
      traumatised. Computerised tomography and fine needle aspiration reduce the risk
      of pneumothorax and haemorrhage in a significant fashion. Personalized
      collaboration between the radiologist, physician and cytologist is a vital pre
      requisite. The indications are discussed notably in cases of solitary pulmonary
      nodules and of mediastinal masses.

PMID- 9036504
TI  - [An unusual case of cardiac insufficiency].
AB  - A 70 year old patient with a past history of a left ventricular cardiomyopathy
      with concentric hypertrophy presented with an exacerbation of cardiac failure;
      radiology revealed bilateral lung infiltrations, predominantly on the right and a
      restrictive ventilatory disorder. The broncho-alveolar lavage revealed a
      lymphocytosis with CD4 prominence. Microbiological examination was negative. With
      a worsening radiological picture despite increased anti-failure treatment a video
      assisted surgical biopsy was performed. The histological examination revealed
      diffuse interstitial pulmonary amyloidosis. This observation underlined the value
      of looking for this rare cause of cardiac failure and pulmonary infiltration in a
      situation where the pulmonary images did not improve on diuretics.

PMID- 9036505
TI  - [Bronchial irritation syndrome following inhalation or urea. Histologic and
      immunohistochemical evaluation].
AB  - We herein report the case of a subject exposed to urea fumes. After exposure, the
      subject immediately experienced throat and chest burning. A few hours later, she
      had cough, dyspnea and wheezing during exercise. The functional pulmonary testing
      performed two months later showed non-specific airway responsiveness.
      Bronchoscopy with broncho-alveolar lavage and bronchial biopsies was performed.
      Biopsies showed injury of the epithelial layer that was atrophic and devoid of
      ciliated cells. There was fibrosis of connective tissue as well as an
      inflammatory infiltrate. Immunohistochemistry stains showed that most of the
      inflammatory cells were T-lymphocytes. There were no degranulated eosinophils.
      The subject was given inhaled steroids. Four months later, bronchial
      responsiveness was normal.

PMID- 9036506
TI  - [Paraneoplastic superior vena cava thrombosis disclosing an ovarian tumor].
AB  - We report the case of a patient who was admitted in hospital for evaluation of a
      superior vena cava thrombosis. The patient exhibited an activated protein C
      resistance due to an arginine-506 mutation in factor V. Thoracic CT-scan showed a
      non-compressive complete superior vena cava thrombosis. Other investigations
      revealed a pleural effusion associated with an ovarian tumor. Pathological data
      of pleural biopsies showed a papillar carcinoma. Ovarian neoplasia revealed by a
      paraneoplasic syndrome was diagnosed. Treatment associated cyclophosphamide and
      carboplatin with anti-K-vitamin was administrated, with a complete remission and
      disappearance of superior vena cava thrombosis at 27 months of evolution. At this
      date, we observed a local pelvis recurrence which was treated with paclitaxel
      associated with surgery.

PMID- 9036507
TI  - [Type AA renal amyloidosis in sarcoidosis].
AB  - Sarcoidosis is an uncommon cause of secondary amyloidosis. We describe in this
      paper the case of a 39 years old patient, with a pulmonary and hepatosplenic
      sarcoidosis. A nephrotic syndrome led to a renal biopsy which showed AA type
      amyloidosis. As no other cause of amyloidosis has been found we admitted that it
      was a result of sarcoidosis which was associated with the unusual inflammatory
      syndrome.

PMID- 9036508
TI  - [Pneumocystis infection in a non-immunocompromised patient].
AB  - Pneumocystis is typically described in the immunodepressed. We report a case of
      pneumocystis occurring in a patient without known depression of the immune
      system. The patient, aged 50, was hospitalised for a diffused infiltration
      pneumonia which developed sub-acutely, and presented with increasing dyspnoea of
      effort, thoracic pain and a disturbances of general health. The initial
      assessment did not reveal any risk factors for HIV infection nor any past history
      of note. The diagnosis of pneumocystis was confirmed by the presence of
      Pneumocystis carinii in the bronchoalveolar lavage from two samples. There was a
      favourable outcome following the prescription of Cotrimoxazole for three months
      and steroid therapy. HIV serology was negative and the sub-population of
      lymphocytes was normal. A search for neoplasia or systematic disease remained
      negative.

PMID- 9036509
TI  - [Measurement of carbon monoxide transfer factor using the apnea method].

PMID- 9036510
TI  - [Bronchial involvement in tuberculosis in children].

PMID- 9036511
TI  - [Biologic diagnosis of whooping cough].

PMID- 9036512
TI  - [Palliative percutaneous treatment under ultrasonographic control of inoperable
      pulmonary aspergilloma: Galenic analysis].

PMID- 9036513
TI  - [Drugs implicated in iatrogenic lung pathology. The STudy Group of Iatrogenic
      Lung Pathology].

PMID- 9036514
TI  - Selected papers from the 1996 International Pre-Olympic Scientific Congress:
      Physical Activity, Sport, and Health. Dallas, Texas, July 1996.

PMID- 9036515
TI  - Proceedings of the meeting of the American Society for Stereotactic and
      Functional Neurosurgery. Marina del Ray, California, March 8-11, 1995.

PMID- 9036516
TI  - [The coral orbital floor. Its value in traumatology. The results of a multicenter
      study of 83 cases].
AB  - A madreporic coral graft was used for orbital floor reconstruction following
      facial trauma. This report presents a multicentric study of 83 patients with a
      follow-up period of 15 to 24 months. The results of this study indicate no
      significant rejection or infection opposed to so many synthetic implants outcome.
      The radiological follow-up demonstrates a partially resorption of the implant
      within about 2 years and its replacements by new bone. Coral implant was used to
      correct enophthalmos or diplopia due to enlarged orbital dimensions. It was
      technically easy to insert and its anatomic shape does not require to be
      fashioned before use. Its inflexibility allows to bridge large bone defects and
      this implant should be considered as an attractive alternative to autogenous
      grafts, avoiding a second surgical site, in reconstructing orbital floor
      fractures.

PMID- 9036517
TI  - [Moebius syndrome: therapeutic proposals from 2 cases].
AB  - Moebius syndrome is a congenital bilateral palsy of the sixth and seventh cranial
      nerves. It results a total absence of facial expression and a severe strabismus.
      Social life is greatly disturbed. Other anomalies may be associated, especially
      other cranial palsies and Poland syndrome. The etiology of this syndrome isn't
      clearly established. Stem necrosis secondary to a vascular deficiency is often
      admitted. We report two observations. We emphasize the importance of a complete
      maxillo-facial treatment including maxillo-mandibular anomaly. Both patient
      underwent orthognathic surgery. The first one for class II and the second for
      class III anomaly. One patient underwent a facial reanimation by temporal muscle
      transfer. Orthognathic surgery must be realized prior to facial reanimation. A
      correction of the strabismus is possible. Moebius syndrome is a rare (200
      observations) but very severe malformation. Maxillofacial surgery is able to
      improve the morphological and relational aspect of Moebius syndrome.

PMID- 9036519
TI  - [Horton's disease: facial manifestations].
AB  - Facial manifestations due to giant cell arteritis are analysed about 102 cases.
      The whole facial vascular territories are involved, so we have many
      manifestations. Diagnosis depends on artery biopsy with Doppler aid.

PMID- 9036518
TI  - [The treatment of prominent ears. A technical note].
AB  - We present a technique for ambulatory treatment of prominent ears derived from
      the Kaye method but which uses some procedures aimed at improving reliability and
      safety.

PMID- 9036520
TI  - [Trismus disclosing Horton's disease].
AB  - The authors report a giant cell arteritis case associating trismus and hemifacial
      oedema in a febrile context. After spontaneous regression of other
      manifestations, the apparition of more typical signs allowed to associate the
      diagnosis of temporal arteritis, later confirmed histologically. Thus, when
      facing a trismus case, even more when fever is present, it seems important to
      associate with the Horton's disease, no matter what the antecedents found at the
      interrogatory be, whether initial or isolated. The Doppler reveals flux
      abnormalities of the superficial branches of the external carotid. The
      examination of facial, temporal and internal maxillary arteries has a good
      negative predictive value in this pathology. It would be useful in therapeutic
      supervision.

PMID- 9036521
TI  - [5 conventional radiographic projections are necessary and sufficient for the
      study of the zygoma. Technics and results].
AB  - Though clinic examination gives us much information, radiology still is essential
      in head trauma. Many standard radiographic projections have been described in the
      past and yet since the eighties it appears that C.T. scanner (C.T.) has become
      absolutely necessary to a great number of us. In fact, C.T. is indispensable when
      there is a matter of vital urgency or when a functional problem appears
      (diplopia). But most of the time high quality standard radiographic projections
      are sufficient. We have selected five radiographic projections: the occipito
      mental's such as Mahoney's or Blondeau or Louisette, the submento-vertical's, the
      rotated occipito-mental's. For each of these radiographic projections we have
      specified the angular definition, the realization techniques, the criterions of
      quality and the results. The use of conventional radiology gives us images of
      which the quality is high enough to allow a precise topographical diagnosis and
      is far cheaper than C.T. So we can assert that standard radiographic projections
      are necessary and sufficient and that the use of C.T. becomes indispensable only
      in the few cases of diplopia or enophthalmia or complicated maxillary fracture.
      In the case of a lateral head trauma, our strategy of radiographic exploration
      will be represented as indicated on picture n degrees 20.

PMID- 9036522
TI  - [Treatment of obstructive sleep apnea syndrome using a mandibular advancement
      prosthesis: review of the literature].
AB  - The treatment of OSAS with prosthetic devices displacing forward and lowering the
      mandible in order to increase the size of the pharyngeal airway is seldom used at
      present. Some recent publications attracted our interest and we deemed it of
      interest to review them. Our work is mostly concerned with objective results as
      assessed by polysomnography, and also with cephalometric changes caused by the
      device. In spite of equivocal results at polysomnography, which seldom met
      commonly accepted criteria of successful treatment, indiscutable therapeutic
      successes have been reported. Therefore, this simple, reversible and cheap
      devices could be advocated in cases of mild or moderate OSAS. However, their role
      in the therapeutic armamentarium of OSAS as well as their indications and
      efficacy need to be better assessed.

PMID- 9036523
TI  - [Facial asymmetry and obstructive sleep apnea syndrome].
AB  - When unilateral mandibular growth disturbances appear early in childhood, they
      usually lead to maxillomandibular deformities. Facial asymmetry, mandibular
      retrusion, and malocclusion are signs also found in hemifacial microsomia. Some
      of these patients develop an obstructive sleep apnea syndrome, which can be
      resolved by surgical-orthognathic treatment. Pre and post-operative
      polysomnograms with recording of oxygen saturation are objective measures of good
      surgical results. Two patients with facial asymmetry and obstructive sleep apnea
      syndrome are presented. Special emphasis is made on treatment planning.

PMID- 9036524
TI  - [Current portable blood sugar analysis equipment--comparison of the MediSense
      Card, Glucometer Elite, Hypocount Supreme and Omnican Control with the glucose
      oxidase reference method].
AB  - Patients as well as medical personnel are increasingly confronted with new
      devices for blood glucose measurement. Devices smaller in size, faster in action
      and easier to handle are being developed by various companies. We investigated
      whether precision and accuracy of recently marketed blood glucose meters would be
      efficient and safe enough for clinical use, and compared the meters MediSense
      Card, Glucometer Elite, Hypocount Supreme, and Omnican Control with our reference
      glucose oxidase method. On average 200 pairs of blood glucose values from
      capillary blood samples of type 1 and 2 diabetic patients were determined using
      two meters of each make. The measurements were performed by one experienced
      technician using blood from the same sample for the meter and the Beckman
      Analyzer 2. For evaluation a linear regression analysis, the percentage of values
      within a maximum deviation of less than 10% from the reference value, and
      clinically relevant models such as Clarke's error-grid analysis and Koschinsky's
      acceptance analysis were used. Combining all analyses, MediSense Card and
      Glucometer Elite showed the least deviations in all blood glucose ranges. For
      MediSense Card 56%, for Glucometer Elite 72%, but for Hypocount Supreme and
      Omnican Control less than 50% of all values were within a +/- 10% range compared
      with the reference method. Clarke's error-grid analysis reflected the best
      results for MediSense Card and Glucometer Elite with 96% and 97% respectively of
      all measurements within the ideal error-grid zone A, whereas this was the case
      for Hypocount Supreme in 85% and for Omnican Control in only 71%. The coefficient
      of variance for measurements in series using 3 different blood glucose ranges was
      acceptable for all devices besides the Hypocount Supreme, but overall performance
      was poor compared to our reference method. Nevertheless, according to
      Koschinsky's clinical acceptance scale even Hypocount Supreme and Omnican Control
      can be classified as clinically acceptable (range 2 from a three point scale).
      The 1994 criteria of the American Diabetes Association, a maximum deviation of
      less than 5% in 100% of measurements, were not met by any device, but after
      training and with proper handling all devices work efficiently enough and are
      safe for clinical use. Nevertheless, companies are urged to seek new technologies
      for blood glucose measurement, as all recently developed devices tested in our
      study did not perform better than known older glucose meters.

PMID- 9036525
TI  - [Why is iodine deficiency once again present in the Berne region?].
AB  - Owing to the progressive iodination of salt in Switzerland (5, 10, 20 mg KI/kg in
      the years 1922, 1965, 1980), iodine deficiency in former endemic goiter regions
      had nearly disappeared. In several areas of the country, urinary iodine had
      increased from below 30 micrograms/24 h (1920) to > 100 micrograms/g creatinine
      (1981-1990). In 1991-1992, however, the 24-h-iodinuria in a subgroup of 160
      examinations out of a total of 289 persons in Berne was again insufficient (norm
      > 150 micrograms J/24 h): mean 121 micrograms/24 h (82 micrograms/l), median
      107.8 micrograms/24 h (67 micrograms/l). Follow-up of one proband in 1991-1992 (n
      = 9) and 1996 (n = 11) yielded average 24-h-iodinurias in the slightly deficient
      domain of (mean +/- SD) 104 +/- 57 micrograms/ 24 h (75 +/- 30 micrograms/l) and
      103 +/- 27 micrograms/24 h (44 +/- 17 micrograms/l) respectively, with a wide
      range (45-258 micrograms l/24 h globally). Possible reasons for the decreasing
      iodide intake in recent years, resulting in the 1990s in a marginally deficient
      supply, are reduced intake of salt in recent decades, increased consumption of
      foodstuffs prepared with non-iodized salt, dietary diversification, and frequent
      meals away from the family table. Therefore, intake of non-iodized salt should be
      avoided in Switzerland.

PMID- 9036526
TI  - [Symposium "Prenatal diagnosis--clinical practice and counseling].
AB  - The growing demand for prenatal diagnosis appears to be making these technologies
      an increasingly normal part of care in pregnancy. Nevertheless, and in spite of
      an expanding lay literature on the subject, every expectant mother has an
      undiminished need for personal information and counselling by her physician. At a
      symposium staged by the Gynecological Clinic, St. Gall, on 1 April 1995 several
      experts highlighted the technical, ethical and psychological aspects of prenatal
      diagnosis as well as the practical problems involved in the counselling and care
      of women and couples in the prenatal situation.

PMID- 9036527
TI  - [Prenatal medicine: development, current status and future perspectives].
AB  - Prenatal diagnosis and therapy are based mainly on the progress of diagnostic
      ultrasound and laboratory methods in genetics. There is a general tendency to
      replace second trimester fetal diagnoses by first trimester approaches.
      Transvaginal sonography and chorionic villus sampling in particular have been
      proven helpful in this context. The aim of all prenatal diagnostic measures is
      fetal therapy in time to prevent untreatable abnormalities. There has been some
      progress in this area; in particular, the application of stem cells for the
      correction of single cell diseases seems to be promising. Because all prenatal
      interventions involve a risk to the mother and especially the fetus, there is a
      concentrated effort to develop non-invasive screening or diagnostic methods.
      Extensive work on the isolation of fetal cells from the maternal circulation has
      revealed that such cells are present physiologically in pregnancy, but further
      trials need to show whether this method is safe enough for routine diagnostic
      use.

PMID- 9036528
TI  - [Ethical problems in the use of prenatal diagnosis].
AB  - The ethical problems of prenatal diagnosis are outlined, with chief emphasis on
      the procedural level. On the procedural level this involves not only ethical
      structuring of the type of prenatal investigations on offer, i.e. acquisition of
      information and care of the patient, but also scientific investigation of the
      individual procedures and their effects on the fetus and pregnancy experience.
      Special attention is focused on the question of establishing legitimate
      indications for the use of prenatal diagnosis. Finally, as part of a discussion
      on human freedom, the fundamental problem of human selection according to
      criteria of genetic efficiency is briefly raised.

PMID- 9036530
TI  - El Nino and infectious disease.

PMID- 9036529
TI  - [Cellular antigen stimulation test (CAST)--applicability in the diagnosis of
      insect toxin allergies].
AB  - In the CAST, blood leukocytes are prestimulated with the cytokine IL-3 and
      exposed to allergen(s). Mainly basophiles react by synthesizing
      sulfidoleukotrienes (sLT), namely LTC4 and its metabolites LTD4 and LTE4. They
      are detected by ELISA technique. 66 patients with suspected allergy to
      hymenoptera venoms were evaluated. Allergic reactions comprised all severity
      grades (I-IV ref. H. L. Mueller). The workup included skin tests (up to 1
      microgram/ml, Pharmacia), measurement of specific serum IgE with RAST-CAP
      (Pharmacia), and CAST with three concentrations of bee (Apis mellifera) and wasp
      (Vespula spec.) venom (Aquagen ALK). A control group of 13 nonallergic, RAST-CAP
      negative individuals was established. CAST demonstrated pronounced variations of
      individual s-LT synthesis in patients and controls. The use of elevated cut-offs
      improved the results, while the use of three allergen concentrations did not
      increase reliability. Diagnostic accuracy of CAST was evaluated by comparison
      with skin tests as the "gold standard". With bee venom and a cut-off at 3
      standard deviations, a sensitivity and specificity of 73%/71% was obtained. Wasp
      venom showed better results at 2 standard deviations, with a sensitivity and
      specificity of 68%/100%. CAST results were not influenced by the severity of the
      allergic reaction nor by the time lapse since the sting had occurred. In
      conclusion, CAST is a valuable test in insect sting allergy. However, established
      methods such as skin tests and RAST-CAP achieve better results. CAST should
      therefore be considered a supplementary method in cases where established methods
      fail. It remains to be shown whether CAST can be used as a parameter for
      monitoring patients who have undergone immunotherapy.

PMID- 9036531
TI  - Too radical for NIH? Try DARPA.

PMID- 9036532
TI  - Monkey virus DNA found in rare human cancers.

PMID- 9036533
TI  - Obesity sheds its secrets.

PMID- 9036534
TI  - Researchers seek new weapon against the flu.

PMID- 9036535
TI  - First nematode-resistance gene found.

PMID- 9036536
TI  - The genomics gamble.

PMID- 9036537
TI  - Key player: Daniel Cohen. ...and a recent recruit.

PMID- 9036538
TI  - Key player: Kevin Kinsella. The industry's top showman...

PMID- 9036539
TI  - Genomics's wheelers and dealers.

PMID- 9036540
TI  - Developing prescriptions with a personal touch.

PMID- 9036541
TI  - Is data-hoarding slowing the assault on pathogens?

PMID- 9036542
TI  - Companies rush to patent DNA.

PMID- 9036543
TI  - Gene tests get tested.

PMID- 9036544
TI  - Organelle genomes: going, going, gone!

PMID- 9036545
TI  - DNA ordering on a lipid membrane.

PMID- 9036546
TI  - [Elastic plate osteosynthesis].

PMID- 9036547
TI  - [Elastic plate osteosynthesis, biomechanics, indications and technique in
      comparison with rigid osteosynthesis].
AB  - Classical stable plate osteosynthesis with its anatomical repositioning, absolute
      stability between fragments and medial support should only be applied to joint
      fractures and spongy bone. In cortical bone, the anatomical reposition connected
      with the plate promotes bone necrosis along the fracture and prevents callus
      formation. Direct cortical synthesis, a method also known as "primary bone
      healing", serves the bone's revascularisation and is not necessarily aimed at
      healing. Thus, this may also be termed "necrosis healing". Along the shaft of
      long bones, elastic plate osteosynthesis, a biological method, is safer than and
      superior to the rigid technique. This even applies to short oblique and
      transverse fractures insofar as nailing does not appear feasible. Elasticity is
      achieved by leaving a flexible stretch of at least 2-4 holes. i.e. as long as
      possible, without screws over the fracture and by employing a titanium plate.
      Thus, there is no punctate fatigue leading to plate breakage. The fitting of
      third fragments is deliberately left out. The same applies to all kinds of
      compression with lag screws, tension devices or DC-gliding holes- and this with
      the intention of allowing micromovements in the fracture's fissure. Periost and
      muscle are not removed and the fracture is not examined. Healing occurs
      spontaneously via a fixating callus forming within the first 3-6 weeks out of the
      periost-soft tissue combination. Histomorphological investigation dates the first
      woven-bone bridges between the fragments to 3 weeks subsequent to the accident.
      In Gottingen University trauma centre, 87 fractures have been attended to over 2
      years using this technique. Despite considerable soft-tissue damage, no delayed
      bone healing, pseudoarthrosis or bone infection has been observed. The risks of
      elastic plate osteosynthesis lie in unbiological and exaggerated reposition
      methods, too short a flexible stretch, and insufficient anchorage of the screws.

PMID- 9036548
TI  - [Arthroscopic capsule-labrum refixation in anterior shoulder dislocation. Primary
      or secondary management?].
AB  - We examined 30 patients with an arthroscopic suture repair for anterior shoulder
      instability in a retrospective evaluation. The follow-up period ranged from 12 to
      58 months with an average of 22 months. Arthroscopic suture repairs were done on
      14 patients (acute group, average age 26.1 years) with acute detached glenoid
      labrum, confirmed on arthro-CT, within 10 days after the injury and on 16
      patients (secondary group, average age 25 years) with chronic should dislocation.
      The evaluation according to the Rowe scale resulted in a mean score of 97.1 for
      the acute group compared with 92.7 for the secondary group. In each group we
      found one recurrent dislocation, which in the acute group was due to an adequate
      trauma. Two of the 14 acute group patients showed a reduction in external
      rotation of up to 20 degrees, compared with 6 patients in the secondary group.
      The external rotation of one patient in the secondary group was reduced to 40
      degrees. The isokinetic muscle strength was decreased in both groups, both for 60
      degrees/s and for 120 degrees/s, to 85% compared with the healthy side. The
      primary surgical therapy of young patients (below 25 years) with an acute
      shoulder dislocation and a detached glenoid labrum is recommended owing to the
      lower redislocation rate, an overall shortened course of treatment and a trend to
      better postsurgical range of motion.

PMID- 9036549
TI  - [Treatment of unstable distal radius fractures with a small AO-fixateur externe
      not bridging the joint].
AB  - This retrospective study investigated the stability of the small AO external
      fixator in a radioradial configuration used in the treatment of 42 mostly
      unstable distal radius fractures (types A-3.2, C-1.2 and C-2.1 according to the
      AO classification). No bone grafting was performed. All cases were documented
      with antero-posterior and lateral X-rays preoperatively, 0, 2 and 6 weeks
      postoperatively and after consolidation. Early functional aftertreatment was
      started one week after surgery. Thirty-six fractures showed a dorsal comminution,
      combined with osteopenia in 18 cases. The mean preoperative radial angle of 17
      degrees was normalized to 25 degrees postoperatively. The mean preoperative volar
      angle of minus 30 degrees was reduced to 12 degrees postoperatively. None of
      these mean angles changed until consolidation. The external fixator was removed
      on average after 7 weeks (range 6-10 weeks) depending on the radiological
      fracture healing. The small AO external fixator in a radioradial configuration
      proved to be stable enough for early functional aftertreatment of the wrist. Its
      stability is related to a proper operative technique and correct indication
      (unstable Colles type with one or two distal fragments). Bone grafting is
      unnecessary if the external fixator is left in situ until bony consolidation.

PMID- 9036550
TI  - [Kapandji corrective operation of post-traumatic disorder of the distal radio
      ulnar joint].
AB  - The Sauve-Kapandji procedure comprises distal radioulnar arthrodesis with
      screwing of the caput ulnae at the basis of the radius after the correction of
      the radioulnar length discrepancy. Therefore the best indications are
      posttraumatic changes of the distal radioulnar joint. At the same time a distal
      ulnar segment resection about 12 mm in length is necessary to restore forearm
      rotation, producing an iatrogenic pseudarthrosis. The proximal ulnar segment
      functionally assimilates to a rotating joint, as could be shown by X-rays.
      Between 1988 and 1993 this procedure was performed in 12 patients. Follow-up
      after an average of 38.2 months showed improvements in forearm rotation of 84%
      for pronation and 60% for supination. All patients had significant pain relief.
      Grip strength also improved, by 55%. No patient got worse postoperatively as
      measured by the score of Gartland and Werley. Neither non-union of the distal
      radioulnar joint fusion nor bony regeneration across the resected ulnar segment
      was seen. The good results are the consequence of adherence to a rigorous
      indication: no preexisting arthrosis at the radiocarpal joint.

PMID- 9036552
TI  - [Supportive composite-hybrid fixation of percutaneous screw fixation of tibial
      head fractures].
AB  - Recent operative techniques with percutaneous screw fixation of the tibial
      plateau require a high level of patient compliance. Geriatric, non-cooperative
      patients and fractures with severe soft tissue injury have had to be excluded so
      far from this therapeutic regimen. Since September 1993, composite hybrid
      fixation, as a combination of ring fixation of the epimetaphyseal tibia with
      monolateral AO fixation of the tibial shaft, has been performed in 12 patients.
      The data were collected prospectively. Fractures were classified according to the
      AO and Moore classification; soft tissue damage was classified according to
      Tscherne and Gustilio. Fixation was performed with the cannulated AO system, 2.0
      mm titanium K wires and 5.0 mm AO Schanz screws. In five patients, additional
      arthroscopic control of the reposition was performed. Average removal of the
      external fixator was 16 weeks postoperatively. Pin-tract infections occurred in
      all patients, mainly in the metaphyseal region. In one patient, a knee infection
      resulted from a subchondral intra-articular pin, which was treated by repetitive
      arthroscopic synovectomy. In two patients, a secondary loss of reposition (5-7
      degrees varus) occurred. Despite a high rate of soft tissue damage (8/12), no
      osteitis or non-union occurred. As an alternative to extensive methods of ORIF,
      supportive composite hybrid fixation offers a new perspective of early functional
      treatment, weight bearing and a rare loss of reposition. It is favored in
      geriatric, non-cooperative patients and in fractures with severe soft tissue
      damage.

PMID- 9036551
TI  - [Development and initial clinical use of an aiming device for distal boring in
      interlocking nailing without roentgen image intensifier for the unreamed tibial
      nail].
AB  - An aiming technique for an unreamed tibial nail was developed, which uses the
      relatively constant distance between the first transverse distal nail hole and
      the anterior aspect of the tibia. This aiming device is set at a distance of 12.3
      mm from the anterior cortex, and fine tuning is finally resolved by use of a
      "working channel" with a 10 mm diameter from the medial side. The aiming system
      was tested in 20 cases in a video-documented prospective study using the unreamed
      tibial nail (UTN, Synthes) between July 1993 and March 1995. In all cases (100%)
      distal locking could be performed without image intensification. With a high
      percentage (55%) of open fractures (3 O3B fractures) the total operation time was
      108 min (median, range 60-180 min). The time for distal locking (always 3 bolts)
      was 15.5 min (median, range 8.0-39.0 min), while the time for proximal locking
      (average 1.6 +/- 0.7 bolts) was 4.5 min (median, range 3.0-15.0 min). There were
      no major intra- or postoperative complications related to the aiming system. The
      major advantages are that it is not necessary to have image intensification for
      distal locking, there is a reduction in radiation exposure for the surgeon, and
      the drill holes are very precise.

PMID- 9036553
TI  - [Proprioceptive capacity of the knee joint area in patients after rupture of the
      anterior cruciate ligament].
AB  - In 30 healthy volunteers with clinically inconspicuous knee joints the
      proprioception of the knee joint was evaluated by an angle reproduction test.
      With the same set-up we documented the effect of an elastic knee bandage. We
      could not document any differences between the left and the right knee joint or
      between men and women, but at the mid-range of motion, proprioception was worse
      compared to the end range of motion. The applied elastic knee bandage
      significantly improved the position sense. Additionally 25 patients with an
      isolated rupture of the anterior cruciate ligament were evaluated. Fourteen
      patients were examined preoperatively 11 after operative ACL reconstruction.
      Preoperatively proprioception was significantly poorer than in the control group.
      We were able to show a positive influence of a knee bandage on the proprioception
      of the injured knee as well. Patients after ACL reconstruction showed no
      significantly better proprioception than the preoperative group.

PMID- 9036554
TI  - [Arthroscopic replacement of the anterior cruciate ligament with a double
      semitendinosus tendon].
AB  - At the university hospital of emergency surgery in Innsburck and at the emergency
      services department of the hospital in Schwaz, anterior cruciate ligament
      reconstruction was performed in 467 patients between January 1992 and September
      1993. In 117 cases, a double semitendinous tendon was used as an autograft. A
      total of 60 of these patients were followed up at an average of 20 months (13-33)
      after reconstruction. The results were rated according to the OAK and the Tegner
      scores. Objective measurements of instability were carried out by a KT 1000
      arthrometer. In addition, 21 patients underwent computer-interfaced dynamometer
      testing using a Cybex 6000. Standardized loading of the thigh muscles was
      performed at angular velocities of 60 degrees/s (3 repetitions) and 240 degrees/s
      (30 repetitions): peak torques and total work were analyzed. The mean age was
      23.5 years (17-55): 48 were male, 21 female. The main reasons for the ACL
      ruptures were sports injuries (51 cases). The patients were classified into three
      groups according to the data of the repair (group 1 reconstruction up to 1 week
      after trauma-28 patients: group 2: reconstruction between the 2nd and 6th week
      after trauma-15 patients: group 3: reconstruction 6 and more weeks after trauma
      26 patients). In group 1. additional ruptures of the menisci. lesions of the MCL.
      and chondromalacia were seen in 71.4%. in group 2 in 73.3% and in group 3 in
      80.8%. The average rating in the OAK score was 90.16 points: 38 patients (55.70%)
      had excellent results. 18(26.09%) were good. 9(13.04%) were fair and 4(5.80%)
      were poor. The Tegner activity score showed a reduction of 0.36 points on
      average. The largest amount of anterior translation was performed with the KT
      1000 manual drawer test (2.29 mm on average compared with the contralateral
      side). Dynamometer testing showed a statistically significant difference in
      flexor and extensor mechanism (compared with the non-involved side) in both peak
      torques and total work. A repeat arthroscopy became necessary in five cases:
      arthrofibrosis in three and incipient joint infection in two cases.

PMID- 9036555
TI  - [Budget analysis in a burn center for severely burned patients].
AB  - The treatment of patients with severe burn injuries is expensive and belongs in
      the hands of specialized burn centres. In our burn centre 257 patients were
      treated from 1991 to June 1995 (between 50 and 60 patients per year except for
      1993 with 77 patients). Patients were evaluated according to the ABSI score (mean
      7) and had mortality of around 15%. The costs range between 3.7 and 4.8 million
      DM per year, the profit lies in the same range. The costs are divided into staff
      costs (1.4-1.8 million DM per year), costs for medical treatment (1.5-1.9 million
      DM per year) and costs for internal services (600,000-900,000 DM per year) such
      as laboratory examinations (247,000-386,000 DM per year) and blood bank (100,000
      215,000 DM per year), the main factors in this category. The different fields of
      costs and profit are compared in this analysis. Possible ways of reducing costs
      are pointed out, and the question of effectiveness of therapy is discussed.
      Conclusions from this analysis are limited by the individuality of each case with
      different clinical courses, the great number of influencing factors and the
      comparably small numbers of patients.

PMID- 9036556
TI  - [Organization of a bone and tissue bank. Consequences for organization of bone
      and tissue banks after HIV and hepatitis C infections].
AB  - The use of non-treated cryopreserved bone allografts has been criticized
      following the publication of new cases of HIV and hepatitis-C infection caused by
      such grafts. However, the "new" cases of HIV infection arose in 1984/1985. when
      HIV testing was not possible. A critical analysis of the German bone bank
      procedures shows that the official guidelines are not adequate. Furthermore, new
      sterilization techniques are propagated for clinical use. This leads to a false
      feeling of security, and does not help to solve the problem of virus transmission
      by way of bone allografts. It is therefore essential that new guidelines for bone
      bank management be developed as a matter of urgency, with due consideration for
      everything known about this problem to date. Our current bone bank procedure is
      presented and the various points in the official guidelines that need updating
      are discussed, including the necessity for 6-month HIV and hepatitis testing
      modified donor screening, and special guidelines for multiple organ donors.

PMID- 9036557
TI  - [Imaging methods in trauma surgery. 1].

PMID- 9036558
TI  - [Blunt thoracic trauma with aortic rupture and lung contusion caused by hoof kick
      in a 15-year-old girl. Diagnostic and therapeutic management].
AB  - The number of published cases of adolescents surviving thoracic aortic injuries
      with accompanying severe thoracic injuries is small. Only 20-30% of all these
      patients reach the trauma center alive. In the present case we demonstrate the
      diagnostic, operative and intensive care management in a 15-year-old girl. The
      exact interpretation of the AP thoracic X-ray in connection with a typical
      mechanism of injury led to the detection of a haemomediastinum. This is very
      important in the further development of diagnostics, because the conventional X
      ray picture does not show significant signs in the case of an incomplete aortic
      rupture. Diagnostic hints have to be derived from the detection of the
      haemomediastinum. The girl was operated on under left heart bypass. Spinal
      ischaemia was absent after surgery, and renal failure also did not occur. The
      adjacent severe lung confusion healed under kinetic therapy with a kinetic
      treatment table without pulmonary complications.

PMID- 9036559
TI  - [Lumbar dislocation fracture with paraplegia after pelvic seat belt injury. Case
      report].
AB  - This report details a traumatic spinal column lesion due to a lap seat belt. A
      healthy 22-year-old woman was involved in a car accident and suffered a lumbar
      luxation fracture at the level L1-L2. She developed acute transsectional symptoms
      with paraplegia and severe hyperpathia in her legs. Plain radiographs (antero
      posterior and lateral projection) and lumbar CT scans demonstrated an instable
      flexion-distraction fracture with ventral compression of the vertebral body of L2
      and ventrolisthesis of L1 over L2. Surgical reposition of the luxation fracture
      and removal of a spinal epidural hematoma was performed 4 h after the trauma.
      Stabilization was achieved by monosegmental dorsal transpedicular spondylodesis
      with a fixateur interne. In follow-up the neurological deficits markedly
      improved. Six months after the trauma, the patient is able to walk, has no
      paresis and no genitourinary disturbances: only mild dysesthesia remains. This
      posttraumatic course confirms that spinal traumas below L1 which spare the conus
      have a favorable prognosis, because the peripheral nerves of the cauda equina are
      able to recover. This injured patient was the only one using a lap seat belt; the
      other four passengers in the same compact car-wearing lap and diagonal seat belts
      suffered no harm. We conclude that lap seat belts are not acceptable as an
      adequate security standard in modern automobile technology.

PMID- 9036560
TI  - [Hemangioendothelioma of the liver in an infant].

PMID- 9036561
TI  - [Caroli syndrome: diagnostic possibilities of magnetic resonance tomography and
      MR cholangiopancreaticography].

PMID- 9036562
TI  - [Factors influencing measuring parameters of beginning arteriosclerotic wall
      changes in carotid arteries in ultrasound].

PMID- 9036564
TI  - [Value of abdominal CT in surgical intensive care patients].

PMID- 9036563
TI  - [Diagnosis of infective spondylitis. Value of bone marrow scintigraphy with 99mTC
      monoclonal granulocyte antibodies in combination with 99mTc-DPD bone
      scintigraphy].

PMID- 9036565
TI  - [Socioeconomic significance of inadequate diabetes management].

PMID- 9036566
TI  - [Immunoprevention of Type I diabetes mellitus].
AB  - The ability to diagnose type I diabetes at an early stage and to identify
      individuals at high risk by immunologic and immunogenetic testing raises the
      possibility of intervention to prevent the disease. At present, three possible
      intervention strategies are being studied: first preservation of residual-beta
      cell mass by nicotinamide, second prophylactic periodic insulin treatment and
      third tolerance induction by oral antigen (insulin) therapy. The rationale behind
      these immune intervention strategies is reviewed and the presently ongoing trials
      are outlined.

PMID- 9036567
TI  - [Islet cell and pancreas transplantation in diabetes: status 1996].
AB  - Replacement of the patient's islets of Langerhans either by pancreas
      transplantation or by isolated islet transplantation is the only treatment of
      type I diabetes mellitus to achieve an insulin-independent, constant
      normoglycemic state. The penalty for this benefit is the need for
      immunosuppressive treatment in the recipient with all its potential risks. Thus,
      indications for pancreas or islet transplantations at present exist almost only
      in patients with end-stage renal disease waiting on dialysis for a kidney graft
      or in diabetics with already established kidney graft being and going to be
      obligated to immunosuppression for this reason, respectively. Pancreas
      transplants alone are primarily performed in only highly selected non-uremic
      patients with extreme problems of the diabetes. Recent studies demonstrated that
      pancreas transplantations finally delay the progression of diabetic secondary
      complications and probably prolong patient's life expectancy. Furthermore, there
      is no doubt on the dramatic improvement of quality of life. However, pancreas
      transplantation confers a certain risk and has its complications whereas islet
      transplantation is a rather minor procedure associated with only small risk, if
      any. Islet transplantation offers the possibility to alter in vitro the islet
      immunogenicity and antigenicity, to induce an immunotolerant state or to
      encapsulate the islets so as to introduce only temporary immunosuppressive
      treatment of the recipient or to obviate the need for immunosuppression after
      islet allo- or xenotransplantation. The effectiveness of this concept was
      demonstrated in animal experiments and may successfully be transferred into the
      clinical situation. In that case the indications for islet transplantations may
      be extended to nonuremic type I diabetics including diabetic children. This group
      of patients is ultimately targetted at by this treatment concept. But, up to now,
      islet transplantations have been performed only simultaneously to or after kidney
      transplantations. However, the progress during the last years period has provided
      evidence that islet transplantation may in principle establish insulin
      independence also in man albeit prolonged insulin independence has been achieved
      in only a small number of cases. The state-of-the-art of clinical islet
      transplantations in type I diabetes mellitus is presented based on a recent
      analysis of the data of the International Islet Transplant Registry kept in
      Giessen. Our own experience at the Giessen Transplant Center with
      transplantations of isolated adult islets of Langerhans in type I diabetic
      patients is supplementary provided.

PMID- 9036568
TI  - [Insulin therapy of Type I diabetes].
AB  - Since the controlled long-term study DCCT has clearly demonstrated that the
      progression of diabetic late complication is highly dependant on metabolic
      control an adaptation of insulin therapy became mandatory. In the eighties first
      successful attempts were made with the so-called Basis-Bolus-Principle (regular
      insulin before meals and depot-insulin at bedtime), the dosis being adapted
      depending on blood sugar tests. Near normoglycemia could only be achieved by a
      very strict time-schedule concerning meal-times and quantity of meals and still
      was accompanied by an increase of severe hypoglycemia. Only with the so-called
      functional insulin therapy it was possible to reach the goal of normoglycemia and
      maintaining the flexibility of patients as well as to reduce the risk of
      hypoglycemia. This type of therapy is based on the optimized adaptation of the
      daily insulin substitution to the physiological need of insulin. The pre
      requisite is a separate substitution of basal and prandial insulin requirement.
      The basal substitution is divided in two to three injections of depot-insulin.
      Prandial insulin is injected according to the amount of desired carbohydrate
      content of the meal. Furthermore, high blood glucose values are immediately
      corrected by regular insulin given s. c. or i. m. To learn the basic knowledge of
      functional insulin therapy, special training is required in which the
      individualized rules have to be determined by self-experiments. This training is
      based on evening ambulatory sessions of 1 1/2 hours weekly during four weeks and
      then two further follow me seminars. The whole course takes three months. More
      than six years of experience with diabetic outpatient clinic at the university
      hospital of Basel have revealed that about 60% of type I diabetics were able to
      learn this therapy and preferred it to the conventional intensive insulin
      treatment. The secret of success of the functional insulin therapy is due to the
      self-determination of the therapy promoting a creative handling with the
      different kind of insulin treatment. The excellent experiences of this therapy
      oblige to offer this treatment to all type I diabetics. Being the achilles-heel
      of each insulin treatment, special efforts must be undertaken to reduce the risk
      of hypoglycemia. An increased risk of hypoglycemia exists with a duration of
      diabetes for more than ten years, or with a severe hypoglycemic attack in the
      past, furthermore with impaired renal function, loss or reduction of hypoglycemia
      awareness and with near-normo-glycemic blood glucose regulation. In this
      situation, a special training of strategies preventing hypoglycemia is indicated.
      As by avoiding low blood glucose values the awareness of hypoglycemia could be
      improved, it is mandatory to make special efforts to reduce or avoid low blood
      glucose values [< 3 mmol]. It is important that in determining the target of
      blood sugar regulation the risk of hypoglycemia has to be considered. In case of
      increased risk of hypoglycemia the target of blood sugar must be elevated. The
      goal of a good metabolic control while minimizing the risk of hypoglycemia and of
      increased flexibility in daily life can only be reached by special efforts of the
      teamwork between physician, diabetes nurse and dieticians with the diabetic
      patient. Different sorts of problems and recommendations of insulin treatment are
      discussed in a supplement.

PMID- 9036569
TI  - [Rational therapy of Type II diabetes].
AB  - Noninsulin-dependent diabetes mellitus is a genetically determined form of
      diabetes, due to impaired insulin secretion by the B-cells as well as to insulin
      resistance of the peripheral tissues. According to the glucose toxicity theory
      hyperglycemia and hyperinsulinemia exist in a vicious circle. Therefore, it is a
      major therapeutical aim to put the B-cell to rest and improve insulin sensitivity
      by a strict control of fasting blood glucose and of postprandial hyperglycemia.
      Furthermore, associated abnormalities within the metabolic syndrome, such as
      hypertension, dyslipoproteinemia and hemostatic disorders should be corrected to
      avoid vessel complications. Therefore, it should be started with basic measures
      as body weight reduction, carbohydrate-rich and fat-poor diet and exercise. If
      these measures fail to achieve acceptable glycemic control, antihyperglycemic
      drugs (acarbose, metformin) are indicated, eventually in a combination with small
      doses of short-acting sulfonylureas. Further impairment of insulin secretion is
      the indication for sulfonylurea and/or insulin application. HbA1c of 7 to 7.5%
      should be the goal of antidiabetic therapy, also for patients in advanced age.
      The main criterion for the choice of antidiabetics is the present insulin
      secretion capacity. Simple indicators in this respect are changes of body weight,
      plasma triglycerides and C-Peptide after i.v. glucagon stimulation. Application
      of insulin in combination with other antidiabetics or in the form of intensified
      insulin therapy should not be too much postponed.

PMID- 9036570
TI  - [Role of physical activity in the therapy and prevention of Type II diabetes
      mellitus].
AB  - Increased physical activity should be part of the treatment for non insulin
      dependent diabetic patients. Increased physical activity delays the onset of non
      insulin-dependent diabetes mellitus (NIDDM) or even prevents the disease in about
      50% of susceptible individuals (positive family history of NIDDM, body-mass index
      > 25, hypertension or gestational diabetes). Regular exercise has been shown to
      lower plasma triglyceride and to increase high-density lipoprotein cholesterol
      levels. Exercise has also beneficial effects on hypertension, body composition
      and fat distribution. Improved glucose tolerance has been achieved in type II
      diabetic patients in as little as one week with an exercise program. The
      beneficial effect of regular exercise on glucose control appears to reflect the
      cumulative effect of transient improvement in glucose tolerance following each
      individual bout of exercise. Increased insulin sensitivity is lost after as
      little as three days of inactivity. Most studies suggest that the maximum benefit
      from exercise is most likely to occur in patients with mild diabetes in whom
      insulin resistance and hyperinsulinemia are present (i.e. patients with fasting
      blood glucose of < 11 mM). The recommended frequency and duration of exercise is
      three times per week or every other day and, as adjunct for weight reduction,
      five to seven times per week for 30 to 45 min. at an intensity of 50 to 70%
      VO2max (or 60 to 80% of maximal the heart rate). Because of the high incidence of
      ischemic heart disease in type II diabetic patients, patients older than 35 years
      of age should undergo a graded exercise stress electrocardiogram. Attention
      should be paid to foot-care and the use of appropriate footwear and diabetic late
      complications, such as autonomic and peripheral neuropathy. Older obese NIDDM
      patients can achieve significant metabolic benefits from low-intensity programs,
      such as daily walking, which can be easily incorporated into daily living. Taking
      the necessary precautions, most patients with diabetes can take part in a
      monitored exercise program safely.

PMID- 9036571
TI  - [Early diagnosis and therapy of diabetic retinopathy].
AB  - Diabetic eye disease, especially diabetic retinopathy including maculopathy, is
      the most common cause of blindness in industrialized countries. However, if
      adequate treatment (photocoagulation, vitrectomy) is started timely, severe
      visual loss from this disease can be prevented in most instances. This paper
      reports on clinical findings, classification and treatment of diabetic eye
      disease. It is emphasized that only an effective screening and prevention
      strategy can lead to a reduction of blindness from diabetic retinopathy.

PMID- 9036572
TI  - [Diabetic nephropathy: diagnosis and therapy].
AB  - Diabetic nephropathy is the most frequent cause for renal replacement therapy in
      many countries. This is mainly due to an increase of renal insufficiency of type
      II diabetic patients. The poor situation could be improved by following measures:
      (a) screening of microalbuminuria for early diagnosis of diabetic nephropathy,
      (b) consequent treatment of known factors influencing the course of nephropathy
      such as poor metabolic control, hypertension, increased protein ingestion or
      smoking, (c) improved cooperation between general practitioner and specialized
      centers concerning treatment of diabetic patients with nephropathy.

PMID- 9036573
TI  - [Clinical aspects, diagnosis and therapy of diabetic neuropathy].
AB  - Diabetic neuropathy is regarded as the most common form of neuropathy in the
      Western industrial countries. At least one third of the diabetic patients is
      affected by a clinically manifest peripheral neuropathy, which can be diagnosed
      by the clinical neurological examination without a great deal of effort. The
      involvement of the autonomic nervous system may be associated with an increased
      mortality. It may result in erectile impotence as well as severe physical
      disability from orthostatic hypotension, fecal incontinence or bladder
      dysfunction and life-threatening complications such as silent myocardial
      infarction or sudden death. Diabetic cardiovascular autonomic neuropathy is
      detected in more than 20% of the patients. The best possible glycaemic control
      including patient education is regarded as the most important therapeutic
      measure. However, additional drug treatment is frequently needed to maintain the
      patient's quality of life. It is usually effective in reducing symptoms of
      diabetic peripheral neuropathy. The therapeutic prospects depend not only on the
      treatment approach but also on the stage of the neuropathic process. Favourable
      effects can be expected particularly in terms of prevention and in the early
      stages of the disease. Treatment options based on the current pathogenetic
      concepts are restricted to clinical trials, except for the antioxidant mode of
      action. The efficacy of symptomatic treatment is limited for some drugs, and
      significant adverse reactions are common. Therefore, before any symptomatic drug
      treatment is initiated, its potential risk should be thoroughly weighed against
      its possible benefit.

PMID- 9036574
TI  - [The diabetic foot].
AB  - Neuropathy, arterial obstruction and infection are involved to varying degrees in
      the development of the "diabetic foot". A careful diagnosis is necessary in order
      to comprehend the various noxa and to introduce the adequate therapy. In case of
      the predominantly neuropathic foot with malum perforans, one must essentially
      proceed in a conservative way; only callosities and osteomyelitic parts must be
      removed. In case of the predominantly angiopathic foot, revascularizing measures
      are most important. After improving the blood flow, the necrotic parts of the
      foot are sparingly resected. As prevention of a possible relapse, two things are
      necessary: accurately fitted shoes in order to prevent pressure points, and
      extremely careful foot care in order to prevent infections.

PMID- 9036575
TI  - [The corrosion and electrochemical properties of new palladium-indium alloys for
      dentistry].
AB  - New palladium-based dental materials were examined in a wide spectrum of pH
      values from 3.8 to 9.6 at 37 degrees C for 315 h. Palladium dissolves in acid (pH
      3.8) media with subsequent passivation (formation of complex compounds); areas of
      passiveness of palladium and its alloys for other pH values were found. The
      potentials of passiveness currents emerging in such cases were defined for all
      media, and corrosion curves of the alloys plotted. A film of palladium oxide
      appearing on the surface of the alloy was found to prevent further corrosion.
      High corrosion resistance in artificial saliva and high chemical inertness of
      palladium-indium alloy was revealed. The mechanisms of selective corrosion of the
      examined alloys and passiveness currents are discussed from the viewpoint of
      modern physical chemistry, and experimental data are explained. Use of such
      alloys in dentistry is shown to hold good promise.

PMID- 9036576
TI  - [The significance of endocrine factors and microorganisms in the development of
      gingivitis in pregnant women].
AB  - 40-100% of pregnant women suffer from the co-called pregnancy gingivitis. The
      cause of pregnancy gingivitis is possible multicausal: increased plasma female
      sex-hormones, alteration in dental plague and perhaps Prevotella intermedia in
      the subgingival plague, together with alteration of immunoresponse. Increasing
      levels of progesterone in the gingiva as well as estrogens due to specific
      receptors affect vascular permeability and exudation, provoke stasis of
      microcirculation, increase prostaglandine E2 formation in human gingiva.
      Decreased gingival keratinization and capability of cell regeneration may affect
      the epithelial barrier. This can perhaps explain the direct dependence between
      progesterone and estrogens increasing and the intensification of gingivitis
      clinical manifestation. The experimental gingivitis model of women during
      pregnancy and post-partum showed identical amounts of dental plague, but clinical
      manifestations were more intense during pregnancy and they had a relation with
      increasing P. Intermedia, no statistical significance was shown in the proportion
      of P. gingivalis. Increasing steroid hormones can substitute for the
      naphtoquinone requirement of P. intermedia. Optimal oral hygiene performed during
      pregnancy reduced gingival swelling, redness and bleeding tendency to levels
      which can be considered as physiologic for the pregnant state.

PMID- 9036577
TI  - [The stimulation of nitric oxide synthesis as a possible protective function of
      the saliva and its disorders in periodontal diseases].
AB  - Effects of mixed non-stimulated saliva on NO synthesis in polymorphonuclear
      leukocytes (PMNs) have been studied. Saliva from healthy volunteers in
      concentration-dependent manner potentiates the NO formation. In patients with
      gingivitis and periodontitis this effect of saliva was altered and in some
      patients saliva did not stimulate NO synthesis or began to suppress it. By means
      of cluster-analysis, a classification of these effects of saliva in periodontal
      diseases has been elaborated. It was shown that in gingivitis and especially
      periodontitis a number of patients with depressed or inverted effects of saliva
      on NO synthesis significantly increased.

PMID- 9036578
TI  - [An evaluation of the safety of hand-held dental photopolymerization reactors].

PMID- 9036579
TI  - [The use of plasmapheresis in treating Sjogren's disease (syndrome)].
AB  - The efficacy of treatment of stomatological manifestations and visceral diseases
      in patients with Sjogren's disease (syndrome) by therapeutic complexes including
      plasmapheresis is assessed. Plasmapheresis was administered to 7 inpatients in an
      intermittent mode with exfusion of up to 1 liter of plasma per session. A course
      consisted of one to three sessions, the total duration of treatment was three to
      four weeks. The efficacy of plasmapheresis in a complex of therapeutic measures
      was assessed from the time course of the clinical picture, results of studies of
      the function of salivary glands, and parameters of metabolic processes and
      immunity. Plasmapheresis helped attain long remissions and improved the general
      status of the patients, this being paralleled by a positive time course of local
      symptoms of the disease and the principal homeostasis parameters.

PMID- 9036580
TI  - [The use of titanium plates and endoprostheses for the mandibular condyles in
      reconstructive surgery of the mandible].
AB  - Potentialities of titanium plates and endoprostheses of the condyle processes in
      replacement of the postoperative defects of mandibular bone tissue are discussed.
      A recently developed Russian kit of titanium plates and instruments and
      specificities of plasty to repair bone defects using this kit are described. The
      results of surgical repair in 5 patients subjected to resection of the mandible
      with exarticulation for tumors or osteomyelitis aftereffects were good: the oval
      of the face and mandibular function were repaired.

PMID- 9036581
TI  - [A case of Kaposi's sarcoma with involvement of the facial skin and the mucosa of
      the right cheek].
AB  - The authors analyzed the clinical and morphological picture of Kaposi's sarcoma
      in a patient aged 38 with involvement of the facial skin and right buccal mucosa.
      Published reports and their own findings brought the authors to a conclusion that
      such a form of the disease is rare, characterized by specific clinical and
      morphological features, and difficult to treat. The prognosis is unfavorable
      because of generalization of the process, the duration of the disease ranging
      from several months to 20 years.

PMID- 9036582
TI  - [The interrelationship between bone tissue structure and the dynamics of the
      process in the surgical treatment of fibrous osteodysplasia of the bones of the
      visceral cranium].

PMID- 9036583
TI  - [Historical stages in the development of maxillofacial surgery and stomatology at
      the N. N. Burdenko Main Military Clinical Hospital].
AB  - The principal trends in the development of stomatological service of the N. N.
      Burdenko hospital from its foundation in 1707 up to the present time are
      presented. The first operations on patients with orodental diseases were
      described in 1710 by the first head of the hospital N. A. Bidloo. Wars had a
      great impact on the development of methods of therapeutic and surgical dental
      care. Original methods of treatment and rehabilitation of patients have been
      developed. At present modern methods of specialized care are used, based on
      integration and computer analysis, use of automated systems for the collection
      and processing of information, and up-to-date treatment and diagnostic equipment.

PMID- 9036584
TI  - [An analysis of the late results in the surgical treatment of patients with
      complex combined nasal deformities].
AB  - Analysis of late results showed that satisfactory and unsatisfactory results are
      most frequent (70%) in patients with combined deformations of the nose. The
      principal causes of recurring deformations after rhinoplasty are a) absence of
      adequate internal fixation of both the dislocated pyramid and the mobilized nasal
      septum; b) omitting the mobilization of the bone part of the septum in case of
      its deformation; c) unjustified wide use of methods of mobilization of crossing
      incisions on the cartilaginous part of the septum; d) no correction of thick
      porous skin at the end part of the nose; e) use of costal allocartilages in
      slight retractions of the cartilaginous part of the ridge of the nose which are
      contoured at the interface, dislocated, and deformed; f) use of costal
      allocartilages as rafters in flattened noses makes the end part of the nose
      thickened and little mobile; and g) use of collodion dressing does not meet the
      requirements of fixation, particularly so in the bone part of the ridge. Hence,
      analysis of late results showed that some of the routinely used methods should be
      revised.

PMID- 9036585
TI  - [The protective properties of the surface layers of the epithelium of the oral
      mucosa].
AB  - Smear impressions of human buccal mucosa keratotic and nonkeratotic zones in
      health were studied by histochemical methods. Differences in the cytochemical
      spectrum of biopolymers contained in nucleus-free scales and nucleus-containing
      cells were revealed. Cationic proteins, acid phosphatase, and nonspecific
      esterase detected in exfoliative epithelial cells are particularly interesting.
      Exfoliative cells of the buccal epithelium play an important role in its
      protective reactions.

PMID- 9036586
TI  - [The use of standard plastic teeth to replace single missing teeth in
      incorporated defects].
AB  - A method for prosthetic repair of dentition defects due to loss of one tooth is
      proposed. A standard plastic tooth is fixed to the tooth limiting the dentition
      defect by means of composite filling material. A cavity similar to Black's class
      III cavity is formed in the artificial tooth.

PMID- 9036587
TI  - [The biological compatibility of the new noble alloy Superpal for metal-ceramic
      dentures].
AB  - Toxic characteristics of Superpal, a dental palladium-based alloy for cermet
      dentures, were studied in a chronic experiment on 20 rats to which it was
      subcutaneously implanted. Analysis of histological findings, blood biochemistry,
      mast cell degranulation test, summarization of subthreshold pulses, and the
      micronucleus test showed that Superpal alloy is biologically inert, nontoxic,
      exerts no sensitizing and mutagenic effects, and may be used for making cement
      dentures.

PMID- 9036589
TI  - [Pediatric stomatology on the boundary of the 20th and 21st centuries: the
      present and the future].

PMID- 9036588
TI  - [Secondary early osteoplasty of the maxillary alveolar process in the combined
      treatment of patients with bilateral congenital clefts of the upper lip and
      palate].
AB  - Gnathometric and roentgenocephalometric studies helped reveal the pathogenesis of
      abnormal maxillary growth in children with bilateral clefts of the upper lip and
      palate. In order to improve the results of treatment of such patients, the
      authors propose a method of secondary early osteoplasty of the alveolar process,
      which may be carried out simultaneously with uranoplasty or separately. Thirty
      six patients were operated on using this technique. Complete repair of the
      alveolar process was attained in 58.3%, partial in 30.6% patients.

PMID- 9036591
TI  - [Chewing gum: the dentist's viewpoint].

PMID- 9036592
TI  - [Dental care in the medical insurance program].

PMID- 9036590
TI  - [The laser therapy of diseases of the periodontium and oral mucosa].
AB  - Authors' methods (patented and certified) of complex (conservative and surgical)
      treatment of periodontal and oral mucosal diseases using new-generation laser
      devices (physiotherapeutic and surgical) have been tested on 588 patients.
      Results of the treatment are reviewed.

PMID- 9036593
TI  - [The determination of the ureolytic and glycolytic activities of human oral
      fluid].
AB  - The authors describe a simple and rapid method for measuring urease and
      glycolytic activity of mixed saliva. It is based on alteration of the color of
      some acid-alkaline indicators during incubation of the saliva with appropriate
      substrata (carbohydrates and urea). Examinations of 32 normal subjects revealed
      that with the developed procedure, the reactions of carbohydrate fermentation and
      urea hydrolysis are rapidly detected in mixed saliva samples, the test taking
      approximately 20 min. Urea hydrolysis was accelerated in 62 patients with
      inflammatory processes in the periodontium, whereas the glycolytic processes were
      inhibited, this indicating an increase in the share of urease-positive
      microorganisms and depression of glycolytic flora. Hence, the described method
      for measuring urease and glycolytic activities of the oral fluid is recommended
      for clinical dentistry to be used for rapid diagnosis of oral diseases and for
      screening examination, as a simple, economic, easily reproducible, and
      noninvasive technique.

PMID- 9036595
TI  - Detection of acquired B antigen by monoclonal anti-B blood grouping reagents.

PMID- 9036594
TI  - Detection of acquired B antigen by monoclonal anti-B blood grouping reagents.

PMID- 9036596
TI  - Detection of acquired B antigen by monoclonal anti-B blood grouping reagents.

PMID- 9036597
TI  - Transfusion: the first decade. Volume 1.

PMID- 9036598
TI  - [The use of laser therapy in correcting hemostatic system disorders in patients
      with chronic pyelonephritis].
AB  - The paper analyzes treatment outcomes in 72 patients with chronic pyelonephritis
      in the phase of active inflammation. The patients have received combined therapy
      including laser blood radiation to correct hemostatic defects. The latter
      manifested as DIC syndrome resistant to antibacterial treatment. Attempts to
      apply transcutaneous laser radiation (TLR) and intravascular laser radiation
      (ILR) showed that DIC syndrome may be cured only in the combined use of the above
      modalities.

PMID- 9036599
TI  - [The characteristics of the action of high-energy lasers on kidney tissues
      (experimental research)].
AB  - Alternative and reparative changes in renal tissue exposed to high-energy laser
      radiation are characterized basing on the experimental findings. It is emphasized
      that hemostasis and ablasticity are secured better if dissection of the renal
      tissue is made by a contact YAG-Nd laser versus routine laser scalpel.

PMID- 9036600
TI  - [The comparative characteristics of the effect of continuous ischemia and
      ischemia with periodic reperfusions on the function and metabolic indices of the
      rabbit kidney].
AB  - Continuous 40-min ischemia and ischemia with reperfusion (10 min of ischemia and
      10 min of reperfusion) induced by ligation of the vascular kidney crus were
      compared in experiments on 17 New Zealand rabbits. Both in continuous and
      interrupted (in period 4) ischemia resulted in the growth of pO2 cortical layer
      which is likely to be due to reduced oxygen utilization of the cells caused by
      metabolic and renal function disorders. Examination of lipid peroxidation
      activity determined similar activation of this process in both ischemic variants.
      In spite of the fact that both continuous and interrupted ischemias induced
      similar hyperoxygenation of the cortical substance and the same activation of
      lipid peroxidation, functional damage was less severe in experiments with
      interrupted ischemia.

PMID- 9036601
TI  - [The surgical treatment of suppurative destructive forms of acute pyelonephritis
      in pregnant women].
AB  - The paper presents the results of surgical treatment of pyodestructive
      pyelonephritis diagnosed in 111 puerperae and gravidae. Suppurative nephritis,
      carbuncle and abscess of the kidney ran as unilateral (94 patients, 84.7%) or
      bilateral (16 patients, 14.4%) process. The diagnosis of pyodestructive
      pyelonephritis of the solitary kidney was made in 1 gravida. The outcomes of
      pyodestructive pyelonephritis in puerperae and gravidae depend primarily on
      individual approach to therapy. Different operative interventions warranted a
      complete response in 97.3% of the gravidae. 96 of 108 gravidae operated on the
      kidneys delivered viable neonates. Early operative interventions in many cases
      preserved the kidney and prevented septic complications. Pyodestructive changes
      restricted to 1-2 segments of the kidney were effectively treated by nephrostomy.
      Bilateral pyodestructive pyelonephritis should be managed step-by-step starting
      at the side of the most evident symptoms. Two-stage bilateral lumbotomy with
      nephrostomy in combination with antibacterial therapy and plasmapheresis
      eliminated septic complications thus allowing normal development of the fetus.
      Nephrectomy is the best treatment in advanced pyodestructive lesion with severe
      life-threatening septic intoxication.

PMID- 9036602
TI  - [Fat-soluble vitamins E and A in the tumor tissue and in the blood of patients
      with renal-cell cancer].
AB  - The level of vitamin E was measured in 31 renal carcinomas and unaffected renal
      cortex taken as control. Two groups were formed in respect to cell composition of
      the carcinoma: 14 tumors composed of clear cells; 17 tumors composed of other
      types cells. Vitamin E concentrations and total lipids in the tumor tissue were
      elevated. Despite a significant positive correlation between levels of vitamin E
      and lipids in cancer tissue, high content of lipids is not the main reason of
      vitamin E accumulation. Concentration of vitamin A measured in 17 carcinomas was
      similar to control as per 1 mg of tissue lipids. Blood levels of vitamin E and
      total lipids in 12 patients with renal cell carcinoma were significantly higher
      than in healthy subjects and returned to normal after nephrectomy.

PMID- 9036603
TI  - [A new method for ureterocystoneostomy].
AB  - The authors offer a new techniques of ureterocystoneostomy using instrument set
      patented in the Russian Federation. The set consists of a detachable metal tube
      and forceps. The tube has a conic end and holds the ureter cut from the bladder.
      The forceps (standard vascular dissector) has jaws 4-5 cm long. The instrument's
      curvature and long jaws make it possible to form sufficiently long submucosal
      tunnel without damage to the mucosa above the tunnel. The ureter is fixed inside
      the metal tube and than is inserted into the tunnel. The technique is low
      traumatic and may be used in congenital pathology of the ureterovesical segment
      in children and adults, in bladder tumors.

PMID- 9036604
TI  - [Varicocele as a symptom of renal venous hypertension].
AB  - Regional trans-scrotal antegrade venotesticulophlebography was used to study
      elements of renocaval anastomosis in 154 males suffering from varicocele. In 153
      patients varicocele was caused by renal vein obstruction and hypertension, in 1
      patient it resulted from iliac vein aneurysm obstructive for pelvic veins. In
      cases of renal vein obstruction on the left all the venous blood runs from the
      kidney along the testicular vein to the pampiniform plexus flowing further to the
      system of the iliac veins. Ligation or endovascular embolization of the
      testicular vein aggravates renal venous hypertension, but varicocele collapsed.
      The authors suggest discussion on methods of varicocele treatment.

PMID- 9036605
TI  - [The surgical correction of hydronephrosis in children (the late results)].
AB  - Surgical interventions on 368 pelviureteral segments were made in 348
      hydronephrosis patients under 14 years old. Bilateral disease occurred in 20
      patients. Resection of the pelviureteral segment was performed with
      ureteropyeloplasty according to Anderson-Hynes-Kucera procedure. Good results
      were observed in 97.82% of cases followed-up from 1 to 2 years after the
      operation. Histological examination of the resected segments revealed structural
      changes in the wall of prepelvic part of the ureter primarily of congenital
      genesis, irrespective of low-polar vessels, high origin of the ureter, its fixed
      kink or narrowing. Irreversibility of structural lesions necessitated conduction
      of resection ureteropyeloplasty with creation of morphofunctionally patent
      pelviureteral anastomosis. High efficacy of the operation supports its
      pathogenetic validity. The effect persisted at the follow-up. After operative
      correction of hydronephrosis medication should be aimed at adequate therapy of
      pyelonephritis and stabilization of sclerosis in renal parenchyma, at improvement
      of immune status and urodynamics. Further follow-up, control of the kidneys in
      search for advanced postobstruction treatment are needed.

PMID- 9036606
TI  - [The intracavernous injection of Edex (prostaglandin E1) in the treatment of
      erectile impotence in persons in older age groups].
AB  - Erectile impotence may be of neuropathic, vascular, psychogenic and hormonal
      origin or may be caused by their combination. This impotence occurs in up to 10%
      of sexually active men. The injection of prostaglandin E1 (PGE1) into the penile
      cavernous bodies results in venous occlusion warranting maximal erection. Edex
      (PGE1) was given to 23 patients aged 43-68 years (mean age 58.9 years) suffering
      from impotence as a result of prostatic cancer (5 cases), postprostatic
      adenomectomy condition (8 cases), chronic prostatitis (4 cases), diabetes
      mellitus (4 cases), chronic alcoholism (1 case), spinal trauma (1 patient). The
      dose (from 5 to 20 micrograms) was adjusted individually. Good, satisfactory and
      poor effects were achieved in 86.2, 13.0 and 4.3% of the patients, respectively.
      In prostatic cancer males on hormone therapy and after adenomectomy the effect
      was obtained in 76.9% (in 10 of 13 males). An old age is not a contraindication
      for intracavernous injections of Edex.

PMID- 9036607
TI  - [The role of detrusor hypoxia in the pathogenesis of urination disorders in
      patients with benign prostatic hyperplasia].
AB  - The aim of the study was to clarify the role of hypoxia of detrusor as a
      component of aging in establishment of urination disorders in patients with
      benign prostatic hyperplasia (BPH). A total of 54 patients were examined. Whether
      the capacity of detrusor to absorb oxygen was affected or not was judged by the
      difference in oxygen tension and acid-base balance in blood samples obtained
      intraoperatively from a radialis, v. mediana cubiti, v. vesicalis in 30 patients
      (experimental group) versus control values (5 females operated for stenosis of
      the distal ureter, ureterovaginal fistulas). The findings provided evidence for
      marked hypoxia of the detrusor diminishing reservoir function of the bladder and
      promoting urination disorders. A course of hyperbaric oxygenation given to 17 BPH
      patients has improved the capacity of the bladder for urine accumulation, reduced
      pollakiuria, especially at night. This supports involvement of detrusor hypoxia
      in pathogenesis of urination disorders in BPH patients.

PMID- 9036608
TI  - [A trial of using EHF therapy in patients with benign prostatic hyperplasia and
      its combination with chronic prostatitis].
AB  - 16 males with benign prostatic hyperplasia (BPH) stage I-II received extremely
      high-frequency (EHF) therapy alone (group 1), 47 BPH males stage I-II and chronic
      nonspecific prostatitis EHF therapy plus antibacterial drugs (group 2). Group 3
      was control. Clinical pretreatment parameters in group 1 averaged: IPSS--16.6;
      QOL--4.1; Qmax--7.2 ml/s, RU-135 ml. Three to six months of treatment brought the
      improvement: IPSS--14.7; QOL--3.2. Qmax rose to 8.3 ml/s, residual urine
      decreased to 126 ml in 11 (68.7%) patients. The effectiveness of the 2 group
      treatment was higher: initial IPSS--18.3, QOL-4.5, Qmax--9.2 ml/s, RU--62 ml
      changed for IPSS--14.1, QOL--3.1 in 43(91.5%) patients, obstruction diminished in
      31 (65.9%) patients (Qmax--10.2 ml/s, RU--53 ml). EHF therapy proved effective
      and safe in BPH alone and especially in BPH combination with chronic nonspecific
      prostatis.

PMID- 9036609
TI  - [Extravesicular retropubic adenomectomy of the prostate].

PMID- 9036610
TI  - [The evaluation of the ratio of free and total serum prostate-specific antigen as
      an additional method in the diagnosis of prostatic cancer].
AB  - The conventional method of prostatic cancer monitoring by determination of serum
      prostatic specific antigen (PSA) was compared to the method of free-to-total PSA
      correlation. The latter proved more informative concerning prostatic cancer.

PMID- 9036611
TI  - [Ionizing radiation and bladder cancer].
AB  - A retrospective analysis of 160 cases of bladder tumors in females revealed that
      in 9 of these cases cancer in the bladder arose 1 to 22 years after radiation for
      uterine and breast cancer. This secondary tumor manifested in 2 females as
      dysuria, in one of them transition cell cancer of the bladder followed Brunno's
      cystitis 2 years after the cystitis diagnosis. The other patients had
      macrohematuria. Being a frequent complication of radiotherapy of pelvic cancer,
      dysuria and macrohematuria should not be considered as a sign of radiation
      induced cystitis. Such patients should be carefully followed up with annual
      microscopic and cytological examinations of residual urine and cystoscopic
      control.

PMID- 9036612
TI  - [Urethral invagination by Solovov's technic in a patient with obliteration of the
      posterior urethra and a small bladder as a consequence of prostatic cancer].
AB  - In cases of missed preoperative diagnosis of prostatic cancer and benign
      hyperplasia, the recovery of unassisted urination in patients who previously have
      undergone transvesicular adenomectomy is often accompanied by traumatic removal
      of the tissues. This leads to severe anatomical changes of the cervicourethral
      segment in the form of postoperative strictures with occasional complete
      obliteration of the posterior urethra. If endoscopic correction of the posterior
      urethra fails to produce a persistent therapeutic effect, it is valid to perform
      urethral invagination into the bladder cervix according to Solovov for
      restoration of the bladder reservoir function, prevention of its fusion and
      progression of chronic interstitial cystitis. The case demonstrates successful
      recovery of the patency of the vesicourethral segment and capacity of the bladder
      in complete obliteration of the posterior urethra and small urinary bladder.

PMID- 9036613
TI  - [Liposarcoma of the spermatic cord].

PMID- 9036614
TI  - [The prognostic factors in bladder cancer patients].

PMID- 9036615
TI  - [Zoladex (ICI) in the therapy of prostatic cancer patients].

PMID- 9036616
TI  - [Antecaval pyelopyelic anastomosis in retrocaval ureter].
AB  - Conservative surgery in retrocaval ureter consists of either ureteric resection
      with ureteroureteroanastomosis or antecaval ureteropyeloanastomosis without
      ureteric resection. Ureteroureteroanastomosis is often complicated by ureteric
      obstruction at the site of anastomosis. The authors offer in retrocaval ureter to
      establish antecaval pyelopyeloanastomosis which excludes anastomosis obstruction.
      The operative procedure is described. Good results were achieved in 3 children
      and 1 adult male treated.

PMID- 9036617
TI  - [The effect of endovascular helium-neon laser therapy on the immune status of
      patients with acute calculous pyelonephritis].
AB  - Cellular immunity was assessed in 48 patients with acute calculous pyelonephritis
      exposed to intravenous He-Ne laser therapy. It was found that endovascular He-Ne
      laser therapy in the study regimens corrects immunological abnormalities arising
      in acute calculous pyelonephritis.

PMID- 9036619
TI  - Prevention of necrotic enteritis in piglets by vaccination of pregnant gilts with
      a Clostridium perfringens type C and D bacterin-toxoid.
AB  - On a large pig farm with a known history of necrotic enteritis 12 pregnant gilts
      were vaccinated s. c. 7 and 2 weeks before expected farrowing with a commercial
      bacterin-toxoid preparation of toxigenic strains C. perfringens type C and D
      (DizevakR-Pliva, Zagreb). At the farrowing the titers of beta-antitoxins in serum
      samples from vaccinated gilts ranged from 9.0 to 26.0 IU/ml with a mean value of
      14.16 IU/ml. Colostral titers varied from 12.0 IU/ml with a mean of 16.12 IU/ml.
      On the second day of life the mean serum titers between litters differed greatly
      from 4.75 to 24.0 IU/ml. By the age of 7 days the average serum titers were
      commonly lower and varied between the litters from 2.25 to 15.0 IU/ml, with a low
      of 1.5 to a high of 16.0 IU/ml in single animals. Ten (8.47%) out of a total of
      118 piglets from vaccinated gilts died during the first 7 days of life but the
      losses were not caused by C. perfringens infection. In unvaccinated control
      animals 18 (15.9%) of 113 piglets died, eleven of them with clinical and
      pathoanatomical signs of necrotic enteritis. The affected piglets predominantly
      succumbed in the first 4 days of life. These data indicate that the investigated
      bacterin-toxoid can be successfully used in immunoprophylaxis of necrotic
      enteritis in piglets.

PMID- 9036618
TI  - [Oxytetracycline in the milk of dairy cows with clinical signs of mastitis during
      the lactation period].
AB  - The objective of this study was to determine the oxytetracycline residues in milk
      from cows with clinical mastitis dosed with two extra-label routes of
      oxytetracycline administration not only during antibiotic's treatment (5 days),
      but also six days after treatment by use of a liquid chromatography method of
      testing with a detection limit of 20 ppb. Both groups of animals were treated
      once daily for five milkings at 24-hour intervals following morning milkings.
      Composite milk samples (equal volumes of foremilk from each quarter) were
      collected during morning and afternoon milkings, mixed together (1:1), and stored
      until analyzed. Milk samples were analyzed just before the first treatment (0
      hour) and ten times at 24-hour intervals. Residue studies in milk cows indicate
      that oxytetracycline passes into milk. Residues in milk were higher for the cows
      receiving oxytetracycline by intramammary route (Tab. I) than for the cows
      receiving oxytetracycline intramuscularly (Tab. II). The highest mean data were
      195.68 mg/kg after intramammary infusion (Fig. 2) and 2.74 mg/kg after
      intramuscular injection (Fig. 3) on the 5th day of the treatment beginning. The
      analysis data showed that oxytetracycline persisted in milk for as long as two
      days after both treatments at the concentration 0.03 mg/kg versus 0.02 mg/kg,
      respectively. No residues were detected in milk of any animal from the 4th day of
      the cessation of the therapy (Fig. 1) as detected by the HPLC method.

PMID- 9036620
TI  - [Effect of flubendazole on Muellerius capillaris in mouflon].
AB  - Muellerius capillaris is the most important pneumonematode of the mouflon kept in
      the Czech Republic. Particularly high values of prevalence and intensity of
      infection are recorded in the mouflon stocks kept in preserves. Numerous
      anthelmintics can be used for pharmacotherapy. Adulticide effect of the drug in
      verminous lung foci should be the aim of administrations. The aim of this study
      was to test anthelmintic efficacy of flubendazole (FBZ) against M. capiollaris in
      mouflon. The study was conducted in 16 mouflons in a small game preserve. An FBZ
      dose of 3 x 15 mg/kg live weight was chosen to be tested. Samples of mixed
      droppings were collected before treatment, during it and after its termination.
      LPG values were determined by larvoscopic examinations. Four (2 x 2) mouflons
      were shot on day 7 and 14 after treatment termination and they were subjected to
      detailed helminthologic examinations (macroscopic description of pulmonary
      verminous lesions, larvoscopy of verminous foci and mucus smears from the
      respiratory tract, larvoscopy of individual droppings). The game were extremely
      willing to ingest the drug applied with feed, the dosing schedule being
      confirmed. Pre-treatment LPG values of mixed droppings (Fig. 1) fell rapidly
      after the treatment started, and the excretion of M. capillaris larvae completely
      terminated beginning on day 7 after treatment termination. Pulmonary and
      coprological LPG findings in the shot mouflons (their description is in Tab. I)
      were minimum, in one animal only (Tab. II), in the others the findings were zero.
      Macroscopic findings (Fig. 2) showed that all shot mouflons had suffered from the
      infection to a large extent before treatment. The therapeutic efficacy of FBZ
      administered at a dose of 3 x 15 mg/kg of body weight can be in general evaluated
      highly positively. The drug administration quickly stopped larvae excretion in
      the mouflon droppings due to adulticide effect in the verminous foci of the
      lungs.

PMID- 9036621
TI  - Babesiosis in a foal.

PMID- 9036622
TI  - [The enhancement of the adaptive resistance of wounded patients to the action of
      the factors in air transport evacuation].

PMID- 9036623
TI  - [Problems in the outpatient diagnosis of cancerous diseases].

PMID- 9036624
TI  - [The current approaches to performing cardiopulmonary resuscitation].

PMID- 9036625
TI  - [The choice of the method for the surgical treatment of duodenal ulcer].

PMID- 9036626
TI  - [Diagnostic and treatment principles in severe combined trauma].

PMID- 9036627
TI  - [The combined treatment of patients with type-2 diabetes mellitus].

PMID- 9036629
TI  - [Autonomic paroxysms: their pathogenesis, diagnosis and treatment].
AB  - In the article the rules about etiology and pathogenesis of vegetative paroxysms
      are stated based on careful analysis of the publications of researches as
      Russian, so foreign authors, and also own experimental and clinical supervision.
      During experimental and clinical researches the modern methods were used,
      enabling to estimate from positions of the system analysis different parts of
      pathogenesis of vegetative paroxysms, and also to offer ways of differential
      diagnostics of the various forms of disease. The application of some new
      preparations and direction of therapy of vegetative paroxysms are substantiated,
      and also the various circuits of treatment of the patients with distinguishing
      forms of given pathology are motivated.

PMID- 9036628
TI  - [New developments in predicting the arrhythmogenic effect of beta-adrenomimetics
      in chronic obstructive lung diseases].

PMID- 9036630
TI  - [Problems in optimizing the management of the territorial organs in medical
      support for the troops].
AB  - In improvement of the management of the medical service the reserves are
      available, enabling considerably to improve system and organization of medical
      maintenance as a whole. They are differentiation of administrative and operative
      management, creation of authorities of territorial management of the medical
      service at three levels (in the garrison, in the zone of responsibility, in the
      district), endowed with the appropriate rights and powers, introduction in the
      daily practice of the modern means of automation and communication.

PMID- 9036631
TI  - [Erythropoietin in the prevention and treatment of anemias (a review of the
      literature)].

PMID- 9036632
TI  - [Viral hepatitis A and B in wounded patients].
AB  - Virus hepatitis A and B have certain characteristics traits in personnel with
      gunshot wounds, especially when the wounds are of medium and high degrees of
      severity. Virus hepatitis A in the injured men is distinguished by shortened
      initial period, predominantly of dyspeptic or mixed type, as well as by grave and
      complicated course sometimes ending with lethal outcome. Virus hepatitis B in the
      injured men is characterized by the absence of pre-icteric period or weakness of
      its manifestations in many cases, by the prevalence of mild forms of the disease,
      as well as by increased tendency to development of chronic forms. During virus
      hepatitis A and B the traumatic disease often acquires grave and complicated
      course. In wounded personnel with hepatitis A the complications develop mainly on
      the background of medium or high degrees of severity of infection, whereas,
      during hepatitis B they develop predominantly on the background of mild forms of
      infection.

PMID- 9036633
TI  - [The antigenic-immunogenic activity of the trivalent polymer-subunit influenza
      vaccine Grippol in a controlled epidemiological trial (2)].

PMID- 9036634
TI  - [An improvement in the toxicological expert assessment of water under field
      conditions].
AB  - In the article the methodical and organized problems of toxicological examination
      of water in field conditions and the ways of there decision are discussed. Is
      shown, that realization of examination and quality surveillance of water in the
      field are rather complicated by absence of a uniform service, which would bear in
      complete volume the responsibility for all parts of field water supply system and
      for final result of their functioning--quality of water. For radical improvement
      of means of the control it is offered to the experts of a chemical type to
      concentrate more attention on traditional and non-traditional methods of
      indication, detection and definition of potent poisonous substances in water. And
      under aegis of medical service will be developed and be improved the biological
      methods of the control of water quality.

PMID- 9036635
TI  - [G. K. Zhukov and military medicine].

PMID- 9036636
TI  - [Encounters with a commander (Georgii Konstantinovich Zhukov)].

PMID- 9036637
TI  - [Milestones in the origin and development of anesthesiology and resuscitation (on
      the 150th anniversary of the first use of ether anesthesia)].

PMID- 9036638
TI  - [The outlook for improving neurosurgical care in the Armed Forces].

PMID- 9036639
TI  - [Epidemiological health surveillance and the protection of the health of
      servicemen (on the issuance of the Regulation on Epidemiological Health
      Surveillance in the Armed Forces of the Russian Federation)].

PMID- 9036641
TI  - [The epidemiological and organizational aspects of the prevention of hospital
      infections].

PMID- 9036640
TI  - [Basic trends in improving the methodological work of epidemiological health
      institutions].
AB  - Main ways of perfection of methodical work of sanitary and epidemiologic
      institutions (SEI) are opened taking into account the modern sights on the given
      problem. The special attention is given to rendering the methodical help from the
      part of SEI experts to the troops medical service on the places, to development
      of science-reasonable recommendations for organization of sanitary and
      epidemiologic supervision and antiepidemic measures, to preparation of the
      methodical documents on questions of antiepidemic protection of the troops.
      Methods of organization of the garrison educational training (conferences) of the
      medical personnel, participation in their preparation and realization of the SEI
      experts are opened. The questions of organizations in SEE of one-monthly military
      epidemiology and military hygiene practice for the medical service chiefs of the
      units and institutions, and also preparation of the younger medical experts for
      antiepidemic protection of the troops are discussed. Estimation of organization
      of methodical work in SEI is given, the approaches and ways of its perfection are
      determined.

PMID- 9036642
TI  - [The epidemiological aspects of pediculosis].

PMID- 9036643
TI  - [The prevention of helminthiases among the troops and the ways to optimize it].

PMID- 9036644
TI  - [Current problems in the prevention of HIV infection among the troops].

PMID- 9036645
TI  - [The assessment of the health status of troop personnel--a basis for the planning
      of measures in disease prevention].

PMID- 9036646
TI  - [The theoretical and practical aspects of the nonspecific prevention of
      infectious diseases among the troops].
AB  - As possible alternative to a complex of sanitary-hygienic measures, directed on
      the infectious diseases prevention, not specific prophylaxis with the aid of
      immunomodulative preparations is offered. Prospects of the immunomodulative
      preparations application is defined by transition to popularized epidemiological
      thinking planned in modern conditions. Strategy of total and selective not
      specific prophylaxis, results of own researches on estimation of preventive
      efficiency of dibazolum and prodigiosanum during acute respiratory disease and
      virus hepatitis A are described.

PMID- 9036647
TI  - [The experience of the functioning of antiepidemic barriers among strategic
      rocket troops].

PMID- 9036648
TI  - [The epidemiological characteristics and laboratory diagnosis of viral
      hepatitides among the Federal troops on the territory of the Chechen Republic].
AB  - The items of information about epidemiologic peculiarities of virus hepatitis
      among military men of incorporated grouping of troops of MoD of RF in Republic of
      Chechnya and about creation of uniform system of laboratory diagnostics in
      interests of etiologic orientation of prophylaxis and control of these infections
      in military groups are submitted. Etiologic structure, the reasons and conditions
      of occurrence of virus hepatitis are established.

PMID- 9036649
TI  - [Experience in preventing acute respiratory viral infections among the troops of
      the Leningrad Military District].

PMID- 9036651
TI  - [The bactericidal efficacy of the Betadine preparation].

PMID- 9036650
TI  - [The trivalent polymer-subunit influenza vaccine Grippol studied in a controlled
      epidemiological trial (1)].

PMID- 9036652
TI  - [Experience in using thermoluminescent dosimeters in individual dosimetric
      control in the medical service units and installations of the Air Defense Corp].

PMID- 9036654
TI  - [200 years of vaccination].

PMID- 9036653
TI  - [The toxicological problems of disaster medicine in the Navy Fleet].
AB  - From position of the uniform concept of the accident medicine the problems of
      toxicological supply of the ships of MNF are considered. Peculiarities of
      chemical accidents in the ship conditions are marked. The question about
      principles of harmful chemical substances regulating, forming air environment of
      ship living quarters is discussed. The prospects of practical use of antidotal
      means, intended for protection of personnel from toxic action of carbon dioxide
      and chemical combinations, causing development of toxic edema of lungs are given.

PMID- 9036655
TI  - [The classic work of Girolamo Fracastoro (on the 450th anniversary of the
      publication of his book "De contagione et de contagiosis morbis et curatione")].

PMID- 9036656
TI  - [The combined action of sinusoidal modulated currents and ultrasound in the
      treatment of chronic gastroduodenitis in children].
AB  - The paper summarizes the results of clinical observations and special
      examinations conducted in 45 children with chronic gastroduodenitis by using
      combined exposure to sinusoidal modulated currents and ultrasound. The dynamics
      of clinical symptoms, functional status of the stomach and its adjacent
      gastroduodenal organs, endoscopic findings, morphological status of the
      gastroduodenal mucosa, gastric mucosal dissemination of Helicobacter pylori,
      systemic and regional humoral immunological parameters, abdominal echography
      indicate high therapeutical efficiency of the combined therapy as compared to
      that performed in controls (without physiotherapy). Mechanisms of formation of
      therapeutical action are clarified, differentiated indications are defined.

PMID- 9036657
TI  - [Inhalation and peroral mucolytic therapy in mucoviscidosis in children].
AB  - The paper summarizes the results of clinical studies of 98 children with
      mucoviscidosis whose age was 7 to 18 years. There is research evidence for
      possibility and expediency of using new classes of mucolytic agents in the
      therapy of mucoviscidosis in children. Analysis of the rheological properties of
      sputum showed the advantage of inhalation route of mucolytics over their oral
      administration. There is evidence for the advantage of mucosolvan over
      carbocysteine and unithiol via all routes of administration, the optimal methods
      of administration and differentiated indications have been developed.

PMID- 9036658
TI  - [The action of an ultrahigh-frequency electromagnetic field (460 MHz) in patients
      with a history of viral hepatitis in the early convalescence period].

PMID- 9036659
TI  - [The use of interference currents and iodobromine baths in the therapy of
      patients with chronic nonobstructive pyelonephritis].
AB  - 30 patients were exposed to interference currents (IC) alone (group 1) versus 34
      patients treated with IC plus iodobromine baths (group 2). After IC action on the
      region of the kidney projection patients of group 1 experienced positive changes
      in cellular and humoral immunity providing an antiinflammatory effect. In group
      2, the improvement was seen in renal and urinary functions, 24-h urinary
      excretion of oxalates and calcium diminished. Interference current proved
      beneficial in chronic pyelonephritis patients with latent inflammation. The
      combined therapy was effective in patients at high risk of lithogenesis.

PMID- 9036660
TI  - [The effect of a low-frequency magnetic field on the clinico-immunological
      indices of patients with chronic inflammatory diseases of the organs of the
      female genital system].
AB  - Low-frequency magnetic field generated by the vaginal inductor used in 120
      females with chronic genital inflammation promoted a decrease in leukocytosis,
      elevation of total population of T-lymphocytes, inhibition of high proliferative
      activity in PHA test. However, marked immunocorrection was not reached.

PMID- 9036661
TI  - [The effect of low-intensity infrared laser therapy on the endocrine function of
      patients with climacteric disorders].
AB  - The authors examined males and females aged 40-65 with menopausal disorders. Low
      intensive infrared laser therapy produced a response both in males and females in
      menopause as evidenced by normalization of FSH, LH levels and elevation of sex
      steroid hormones.

PMID- 9036662
TI  - [The optimization of the duration of the sanatorium-health resort treatment of
      patients with neurological manifestations of spinal osteochondrosis (I)].
AB  - Short-term mud therapy (10 daily peat [correction of moor] applications) has been
      performed in patients with neurological symptoms of spinal osteochondrosis. Such
      short-term courses are indicated in the absence of exacerbation of the basic and
      associated diseases under domination of the radicular and reflex syndromes. High
      efficacy and good tolerance of the treatment are confirmed by
      vertebroneurological investigations and functional diagnostic tests.

PMID- 9036663
TI  - [Cold-assisted electrical nerve stimulation (CAENS)--a new method of analgesia].

PMID- 9036664
TI  - [The UHF therapy of hypertension patients].
AB  - Ninety-three patients with stages I-II essential hypertension treated with
      microwave electromagnetic fields (460 MHz) with collar exposure were studied.
      Microwave therapy was found to produce an antihypertensive effect in 74%, chiefly
      by lowering the increased cardiac output, to improve blood pressure responses to
      exercises, to make catecholamine excretion normal and coronary and cerebral
      circulation better.

PMID- 9036665
TI  - [Occupational therapy in the rehabilitation of patients with pathology of the
      hand].

PMID- 9036666
TI  - [The role of physical balneological factors in the treatment of occupational
      diseases].
AB  - The authors review the results obtained in the treatment of some occupational
      diseases using physical factors. In osteoarthritis patients exposed to fluorine
      compounds good results were achieved at employment of decimeter-wave therapy
      combined with mud applications or sulfurated hydrogen baths. Patients with
      scapulohumeral periarthritis benefited from combination of EHF therapy with
      alternating magnetic field. Initial lead intoxication was effectively treated
      with magnetotherapy. Subjects with vascular pathology occupationally exposed to
      high temperature responded to magnetolaser impact on reflexogenic regions of the
      heart.

PMID- 9036667
TI  - [The dynamics of the immunological indices of children from regions around
      Chernobyl during health-resort treatment].

PMID- 9036668
TI  - [The tasks of organizing and managing the monitoring of natural therapeutic
      resources and of medical health-promotion locales].

PMID- 9036669
TI  - [A new principle in the organization and functioning of the sanatorium
      institutions of a separately considered health-resort region].

PMID- 9036670
TI  - [Physiotherapeutic proscribing in gynecological practice (a short guidebook)].

PMID- 9036671
TI  - [Nondrug methods for correcting the immune system in the rehabilitative treatment
      of patients with a history of viral hepatitides].

PMID- 9036672
TI  - [The 60th anniversary of Yevpatoriya as a model children's health resort].

PMID- 9036674
TI  - [The problems of the rehabilitation and nondrug therapy of patients with
      bronchopulmonary diseases (based on materials from the 6th National Congress on
      Diseases of the Respiratory Organs)].

PMID- 9036673
TI  - [The pharmacological and laser correction of disorders of the blood
      microcirculatory bed in myocardial ischemia].
AB  - Microhemocirculatory changes in the ischemic myocardium concurrently exposed to
      low-intensive He-Ne laser, finoptin (145 micrograms/kg body weight) and
      perlinganit (25 micrograms/kg body weight) were experimentally studied in 50
      Chinchilla rabbits. Drug and laser were daily used after 30-day inactivity for 7
      days. There were anti-ischemic effects of He-Ne laser and perlinganit in
      increasing the number of functioning capillaries and in enhancing their
      functional activity. Microhemocirculatory changes induced by finoptin were less
      significant than those caused by perlinganit.

PMID- 9036675
TI  - [The use of physical factors in treating chronic arterial insufficiency of the
      lower limbs].

PMID- 9036676
TI  - [Intravenous laser irradiation of the blood at the health-resort stage of
      treatment for bronchial asthma patients].
AB  - The efficiency of spa treatment in combination with intravenous He-Ne laser
      (wavelength 0.63 microns) radiation of the blood was studied in 152 patients with
      bronchial asthma of endogenous genesis, mainly with that of moderate severity. By
      the end of 24-day treatment there were clinical improvements, better external
      respiratory parameters, and alleviated inflammation.

PMID- 9036677
TI  - [Value of diuretics in hypertension].
AB  - Diuretics still remain a cornerstone in the treatment of hypertension. Adverse
      effects such as disorders of the carbohydrate and lipid metabolism as well as
      development of hypokalemia or hypomagnesemia are obviously directly correlated to
      the administered dosage. Therefore, there is increasing agreement for low-dose
      drug therapy. In contrast to hydrochlorothiazide treatment, metabolic disorders
      are less commonly encountered with indapamide therapy. A pronounced diuretic
      efficacy is linked to the combined use of diuretics which act on different
      segments of the nephron (for example administration of a loop diuretic together
      with a thiazide). In chronic renal failure indapamide appears to be superior to
      hydrochlorothiazide considering preservation of renal function. In contrast to
      thiazides, indapamide is the therapy of choice in patients with diabetes.

PMID- 9036678
TI  - [Effects of diuretic therapy on electrolyte and acid-base homeostasis].
AB  - The use of diuretics leads to a negative sodium and fluid balance without primary
      effects on serum sodium concentration. This parameter is regulated by the
      activity of the antidiuretic hormone (ADH) system. Secondary changes in other
      electrolyte systems and in acid base homeostasis also are induced by diuretic
      therapy. Especially diuretic induced hypokalemia is important as it is
      responsible for the excess mortality observed in patients with diuretic treated
      essential hypertension and cardiac abnormalities. All adverse metabolic effects
      of diuretic therapy are, in contrast to the antihypertensive action, dose
      dependent. Changes in fluid and electrolyte metabolism induced by diuretics occur
      within the first 2 or 3 weeks after initiation of medication. Counterregulatory
      mechanisms are activated and a new steady state is established. Serial laboratory
      determinations after this period are not necessary as long as this steady state
      is not affected by additional events (like a change in therapy or diet as well as
      the occurrence of vomiting or diarrhea).

PMID- 9036679
TI  - [Diuretics and diabetes mellitus].
AB  - The term "diuretics" describes a concerning pharmacological action and side
      effects heterogeneous class of drugs. The special advantage of using diuretics
      includes reducing edema and expanded plasma volume often associated with
      hypertension and cardiovascular disease. Diuretics are one of the 5 major classes
      of antihypertensive agents recommended for the initial drug therapy of
      hypertension. However, currently treatment of hypertension with diuretics is
      controversial, because of potentially adverse effects on the cardiovascular risk
      profile, including deterioration in glucose control especially in patients with
      impaired glucose tolerance. Additionally there is concern about excess mortality
      associated with diuretic therapy and diabetes mellitus. The metabolic side
      effects on glucose metabolism and lipid profile are related to the type of
      diuretic and its dosage. The adverse effects of thiazides on insulin action,
      glycemia and lipid profile are dose dependent and can be minimized by using low
      doses. In contrast, indapamide seems not to alter glucose metabolism and lipid
      profile. The choice of diuretic depends on concomitant disease. In patients with
      nephropathy potassium sparing agents should not be used, however furosemid can be
      used even in high doses. Beside focus on indication of diuretics in patients with
      diabetes and their metabolic side effects treatment of therapy resistant
      hypertension in these patients are discussed in this review.

PMID- 9036680
TI  - [Diuretics in renal failure].
AB  - The indications for the use of diuretics in patients with renal failure are edema
      and hypertension. An ancillary measure is dietary sodium restriction which
      permits reduction of the diuretic dose and reduces the frequency of diuretic
      induced side effects. The natriuretic action of diuretics is attenuated in renal
      failure both for pharmacokinetic and pharmacodynamic reasons. The most important
      cause for reduced efficacy of diuretics in renal patients is binding of diuretics
      to proteins within the tubular lumen so that the absolute free concentration of
      diuretics is diminished. Further important reasons for the diminished increment
      in urinary sodium excretion that is seen in patients with renal failure include
      a) reduced number of nephrons (i.e. reduced functional mass) and b) intrarenal
      compensatory mechanisms which increase sodium activity and tubular reabsorption
      of sodium. These difficulties can be overcome by dietary sodium restriction, by
      selection of higher doses of diuretics, by selection of appropriate intervals of
      administration and by combination of loop diuretics and thiasides. In order to
      recognize side effects resulting from excessive diuresis with hypovolemia and
      increase of serum creatinine concentration from prerenal causes it is necessary
      to closely monitor the patients.

PMID- 9036681
TI  - [Etiology and treatment of diuretic resistance].
AB  - Basically the cause of the resistance to diuretics can be found out. Essential is
      a detailed knowledge of the physiology and pathophysiology of volume regulation
      as well as renal water and electrolyte excretion. To get diagnostic and
      therapeutic access to diuretic resistance main efforts have to be put into the
      work up of current diagnostics and therapy of the main disease (heart failure,
      liver failure, nephrotic syndrome, and renal failure) as well as the symptomatic,
      drug related volume regulation (exact balancing of fluid intake and excretion
      with and without diuretics) in these severely ill patients. Has the underlying
      cause for resistance to diuretic medication been found, therapy is generally easy
      and effective. It might be unsuccessful in patients with severe impairment of
      renal function. Then the only way may be extracorporeal fluid removal.

PMID- 9036682
TI  - [ACE inhibitors and the kidney].
AB  - Treatment with ACE inhibitors results in kidney protection due to reduction of
      systemic blood pressure, intraglomerular pressure, an antiproliferative effect,
      reduction of proteinuria and a lipid-lowering effect in proteinuric patients
      (secondary due to reduction of protein excretion). Elderly patients with diabetes
      melitus, coronary heart disease or peripheral vascular occlusion are at risk for
      deterioration of kidney function due to a high frequency of renal artery stenosis
      in these patients. In patients with renal insufficiency dose reduction of ACE
      inhibitors is necessary (exception: fosinopril) but more important is the risk
      for development of hyperkalemia. Patients at risk for renal artery stenosis and
      patients pretreated with diuretics should receive a low ACE inhibitor dosage
      initially ("start low - go slow"). For compliance reasons once daily ACE
      inhibitor dosage is recommended.

PMID- 9036683
TI  - [Renal side effects of angiotensin converting enzyme inhibitors].
AB  - Angiotensin converting enzyme (ACE) inhibitors are used widely in the treatment
      of hypertension and congestive heart failure. An increasing number of patients
      with chronic renal failure is treated with ACE inhibitors because of their
      antiproteinuric effect. In patients with diabetic nephropathy ACE inhibitors also
      slow the progression of renal failure. Direct drug related nephrotoxic effects,
      like the induction of proteinuria, glucosuria or an interstitial nephritis are
      rare events. The often observed reduction of the glomerular filtration rate after
      the induction of an ACE inhibitor therapy is due to the specific intrarenal
      action of these agents and therefore not an adverse drug reaction.

PMID- 9036685
TI  - [Crisis in medical ethics].
AB  - There is a disproportion between diagnostic and therapeutic medical achievements
      and the doctor/patient relationship. Are we allowed to do everything we are able
      to do in medicine? People are concerned and worried (genetic technology, invasive
      medicine, embryos in test tubes etc.). The crisis of ethics in medicine is
      evident. The analysis of the situation shows one of the causes in the shift of
      the paradigma-modern times to postmodern following scientific positivism-but also
      a loss of ethics in medicine due to an extreme secularism and to modern
      philosophical trends (Hans Jonas and the responsibility for the future and on the
      other hand modern utilitarism).

PMID- 9036684
TI  - [Results of an open study for evaluating the effectiveness and tolerance of
      adjuvant administration of the ISF nutrient program in HIV positive patients].
AB  - HIV positive patients usually show a gradual deterioration of their general
      condition and the laboratory key values which are accompanied by the resulting
      negative effects on their subjective condition. This study showed a very good
      stabilization of HIV positive patients by using the complex ISF nutrient program
      over a period of ten or 15 months. Only a very low proportion of antiviral and
      antibiotic supply had been given. The ratio did not change over the entire
      testing period of 15 months. The mortality rates observed here were a fraction of
      the AIDS mortality rates that are otherwise published. The data of this study
      also show a very good benefit/risk relationship for the patients, which can be
      derived from the overall favorable statements on the tolerance.

PMID- 9036686
TI  - [Comment on planned evaluation regulation of the Austrian Ministry of Science for
      university medical education].
AB  - Austria till now operates without any evaluation of medical university teaching.
      Now the science-ministry has circulated the draft of an edict which we comment as
      follows: 1) The new measures should be in a way that alone by their existence
      amelioration of quality appears. Also they should provide better communication
      between teachers and students (which has gone lost a great deal in the mass
      university of today). 2) Examinations are the worst instruments for quality
      raising. We propose installation of a flying commission which talk things over
      with teachers and with students and thus forms a living bridge to raise
      communication. We think that things should rather not be done in anonymity, but
      more in steady communication between teacher and student. 3) There should be
      evaluation of evaluation and the named commission should ensure a steady dynamic
      evolution of it. 4) Main thoughts are that university-teachers are evaluated as
      well for their quality of teaching as for their endeavour to optimate it, whereas
      now only "papers" and scientific output is measured. The student should learn own
      responsibility, overall knowledge and better communication. Only thus we shall
      educate new doctors that approach a humanistic ideal instead of being "medicine
      apparatschiks".

PMID- 9036687
TI  - [Rehabilitation as interdisciplinary responsibility--the medical specialty
      "physical and rehabilitative medicine"].
AB  - Physical and rehabilitation medicine is an independent medical subspecialty and
      is not derived from "physics" but from "physis-nature". Beside the elements of
      specific movements, it does use physical components such as heat, cold, light,
      water, and electricity for therapeutic purposes. Physical medicine and
      rehabilitation has always been a discipline with own methods, issues, and own
      areas of research and theory. The treatment techniques of this specialty are
      summarized under the term "physiotherapy". Its methods, which also contain
      balneology and medical climatology, are using physical and physiological
      principles of order in the organism. The application of this therapy happens for
      the training of impaired functions, influence of pathogenetic processes causing
      pain, and for the activation of the body's regeneration capacities. Physiotherapy
      is not limited to certain diseases or stages of illness but may prevent, abolish,
      or weaken malregulation of functional units, especially when used in repetitions.
      A particular focus of the rehabilitation is to address the still remaining
      functional reserves of an injured organism in a way that a compensation can be
      reached as close a possible to the etiological point of the pathogenetic chain of
      causes. Declared goal of the physiotherapy is the induction and optimization of
      healing processes. Due to this interdisciplinary approach, physical and
      rehabilitation medicine is an essential part for almost every medical
      subspecialty. Because of the increasing importance of this discipline, the
      specialist for physicial and rehabilitation medicine was introduced in Germany in
      1992.

PMID- 9036688
TI  - [Cardiologic rehabilitation. An orienting overview].
AB  - The European Society of Cardiology has dealt in detail with concepts of
      cardiological rehabilitation in 1992 and has published guidelines. According to
      the opinion of this society, the organization of cardiological rehabilitation can
      differ among the European countries considering the socio-economic structures,
      legal and insurance regulations as well as national traditions. Guidelines for
      the standards of cardiological rehabilitation have to be flexible and adaptable
      to the organization of each European country. According to the opinion of Muller
      Fahrnow, the beginning of modern medical rehabilitation in the Federal Republic
      of Germany is clearly linked to the development of concepts for cardiological
      rehabilitation at the end of the sixties and beginning of the seventies with a
      holistic approach under consideration of a kinetotherapeutic and psychosocial
      focus. A countrywide introduction of the concept of the following curative
      treatment at the end of the seventies by the insurances contributed to a
      significant stabilization of the new qualities of rehabilitation and, again the
      cardiological rehabilitation played an important role (Muller-Fahrnow W., 1994).
      This paper demonstrates basic elements and structures of the cardiological
      rehabilitation in an orientating manner and contains conclusions about the future
      development.

PMID- 9036689
TI  - [Gastroenterologic and hepatologic rehabilitation today--on changes in
      indications and contents].
AB  - The rehabilitation in gastrointestinal diseases has experienced the introduction
      of new concepts. Regional health resorts (i.e., mineral springs, climate or mud
      baths) do not play a role anymore. Today, rehabilitation cliniques are teaching
      and training centers for chronic patients with multiprofessional teams. The need
      for rehabilitation cannot be derived from the diagnosis alone or the duration of
      the illness but from the severity of the symptoms and/or additional psychosocial
      problems. The order of the application of different techniques during medical
      rehabilitation differs from patient to patient and necessitates a definition of
      the rehabilitation goal. Chronic inflammatory bowel disease, chronic
      pancreatitis, and chronic liver diseases are explained as an example.
      "Rehabilitation of gastrointestinal or metabolic diseases' is often better
      described with a model of progression than with the traditional model of
      disablement. Therefore, a network of clinical and ambulant rehabilitation as well
      as an entanglement of institutions providing hospital care and after-care is
      required.

PMID- 9036690
TI  - [Rehabilitation in asthmatic diseases].
AB  - The early recognition of an asthmatic disease is important for optimal treatment
      and rehabilitation with a long lasting success. The knowledge, that bronchial
      asthma is always accompanied by a chronic inflammatory process of the airways,
      necessitates the early application of antiphlogistic substances like
      glucocorticoids as well as weaker substances like DNCG and nedocromil. Therefore,
      the basic therapy of patients with asthma of the severity II to III should be a
      combination of beta-2-agonists and antiphlogistic drugs. The pharmacological
      therapy has to be accompanied by a practical health training (ashtma and
      antiobstructive training). This is the only way to accomplish an optimal
      treatment with a correct inhalation, professional usage of ventilation aids, and
      a convincing recording of peak-flow-values. Rehabilitation of patients with
      asthma is team work. Beside physicians, co-therapists like psychologists,
      dietitians, and trained nurses have to be employed.

PMID- 9036691
TI  - [Current aspects of neurologic and neurosurgical rehabilitation in ambulatory
      medicine].
AB  - Nearly all neurological and neurosurgical diseases can cause lasting
      disabilities. Therefore, neurorehabilitation is needed. The German Pension
      Insurance Association has developed a concept of phases working as a chain of
      treatment, rehabilitation and care. This was confirmed as the one official system
      by the German Federal Society for Rehabilitation consisting of all social
      insurances and wellfare sponsors. The goals and tasks of each phase are defined
      by the functional status of the patients and their requirements for recovery. The
      costs are mostly determined by the social health or the social pension
      insurances. Different professions (physicians, nurses, physiotherapists,
      occupational therapists, speech therapists, (neuro-)psychologists, social
      workers) have to cooperate as a "therapeutic team" to improve the patient's
      impairments, disabilities and handicaps and to make full use of their individual
      resources of recovery. Only this can be the basis for valid prognostic decisions.
      In the long term treatment and care of the general practitioner, stroke patients
      are the most important group. Special problems are seen after traumatic brain
      injuries. Other relevant diagnoses are Parkinson's syndrome, multiple sclerosis,
      diseases and injuries of the spinal cord or the peripheral nervous system. In
      many patients, special aids have to be prescribed for several aspects of human
      living.

PMID- 9036692
TI  - [Psychosomatic rehabilitation].
AB  - Containing 14,000 beds on wards, the psychosomatic rehabilitation in hospitals
      has a significant part in the treatment of psychosomatic and somato-psychological
      diseases where psycho-social parameters play an etiological role. This work may
      be aggravated by the fact that these diseases are often recognized too late and
      that the patients are admitted to specialized hospitals in a state of chronic
      illness. Nevertheless, these hospitals are working with great success especially
      regarding the reduction of costs in the period after discharge, reduction of the
      time being incapable to work, in patient days, medication, and medical
      attendance. Beside these parameters of cost reduction, the success in treatment
      also contains the improvement of subjective parameters such as satisfaction of
      living, relationships, and every day life. Psychodiagnostic hints are given for
      the on time diagnosis of the mentioned disturbances allow an early and adequate
      treatment.

PMID- 9036693
TI  - [Psychological contributions to rehabilitation in ambulatory health care].
AB  - Concepts and theories of psychology are represented which are suitable to enrich
      rehabilitation medicine in the outpatient medical attendance. First, the
      understanding of rehabilitation medicine is discribed as a comprehensive care to
      ensure handicapped persons remain incorporated in family, society and occupation.
      Second, special fields of psychology sciences are explained, which contribute to
      reach these aims of rehabilitation, especially pedagogics and health psychology,
      medical and clinical psychology and behavioural medicine as well as behavior
      therapy. Third, there are chances discussed to comprise psychologists in a
      comprehensive rehabilitative treatment.

PMID- 9036694
TI  - [Responsibility for the individual or the whole? Ethical considerations on
      medical responsibility].
AB  - Physician's patients are often faced with a conflict of interests between the
      benefit and other interests (society, institutions). This problem has emerged in
      medical history since the 18th century when the traditional loyalty towards the
      individual patient was challenged by a social orientations in the physician's
      ethos. Current bioethical theories regarding this professional conflict of
      interest are discussed and applied to allocation problems in HMO-health plans. It
      is argued that the conflict of interests can only be solved if doctors set their
      professional priority on the healing relationship towards the individual patient.

PMID- 9036695
TI  - [Possibilities of therapy and rehabilitation of patients with urinary
      incontinence].
AB  - Rehabilitation of incontinent patients is an interdisciplinary challenge. Many
      therapeutical options in gynecological urology reveal an optimal rehabilitation
      of these patients. In the last years, a great scientific progress in the area of
      neurourology offers patients with severe dysfunction of the lower urinary tract
      (e.g. spinal cord injury) new concepts to improve their urological problems.

PMID- 9036696
TI  - [Enteral feeding].
AB  - In patients with normal gastrointestinal functions, enteral nutrition is safe,
      efficious and inexpensive. The knowledge of enteral products and the correct
      selection of application techniques are important for a successful therapy. Long
      term enteral nutrition of different subgroups of patients is possible by
      percutaneous endoscopic gastrostomy (PEG). Many complications may be avoided by
      changing the modalities of application.

PMID- 9036697
TI  - [Health promotion in the 2nd half of life. A modular concept for public health
      insurance patients: the preventive program "healthy aging"].
AB  - A modular concept for persons members of health insurances: the prevention
      programme entitled becoming old and remaining healthy. Prevention is sensible in
      the second half of the life span. In these later years, key objectives include
      such concrete classical themes like nutrition and mobility as well as prevention
      of falls and psychosocial support for family care providers. Such prevention
      requires a multi-step procedure if the goal of a self-determination in health
      behavior is to be reached. The prevention programme "Becoming Old and Remaining
      Healthy", an example of such a concept, is presented in this article. Selected
      components of these programme should give an impression how psychological and
      educational approaches can be used to help students understand the health
      implications of their own life circumstances. This paper is to familiarize the
      reader with the basic concept of prevention and health promotion.

PMID- 9036698
TI  - [Evidence-based medicine: popular nonsense, old wine in new bottles or current
      necessity?].
AB  - This article is intended to provide a comprehensive overview regarding motives,
      implications, aims, history, underlying principles, and methods as well as
      criticism and potential impact of "Evidence Based Medicine" (EBM). The term was
      defined and the movement initiated by British and Canadian clinicians
      epidemiologists. So far, a translation and national adaptation remain to be
      established. It seems that EBM is suited to compensate for many irrationalities
      within our clinical practice and health care system. Not only should the
      underlying principles, aims, methods, and techniques of EBM be considered in
      clinical practice and primary care in Germany. They should also be emphasized
      during medical training and postgraduate education and in the needs-oriented
      distribution of scarcening resources.

PMID- 9036700
TI  - [Intramyocardial electrocardiogram (IMEG) in diagnosis of humoral rejection after
      heart transplantation].
AB  - Measuring intramyocardial ECG amplitude is a clinical non-invasive procedure used
      for diagnosing rejection after heart transplantation. In recent years, as the
      importance of humoral mediated rejection has increasingly been recognized, the
      fact that endomyocardial biopsies often produce false negative results due to the
      absence of lymphocytic infiltrates has become a matter of concern. In order to
      test the reliability of IMEG diagnosis of this form of rejection, heterotopic
      neck-heart transplantation was performed on eight beagles which were previously
      sensitized through several skin transplantations. Over the course of the study
      IMEG registrations were performed daily as well as echocardiographic examinations
      to determine left ventricular wall thickness and maximal diastolic relaxation
      velocity. Donor-specific antibodies in serum (IgG, IgM) were also determined
      daily. Myocardial biopsies, performed once every 2 days, were examined for the
      presence of edema and lymphocytic infiltrate (according to the guidelines of the
      International Society of Heart and Lung Transplantation, ISHLT) and examined
      under immunofluorescent microscopy of IgG and IgM. Under triple drug
      immunosuppression with cyclosporine A, azathioprine, and cortisone accelerated
      rejection occurred on the fifth postoperative day (range: 4th-5th). All eight
      episodes were detected through IMEG diagnosis (sensitivity 100%), while the
      myocardial biopsies graded according to ISHLT guidelines indicated only one case
      of relevant lymphocytic infiltrate (Grade 3A) (sensitivity 12.5%). In each case
      rejection was recognized so early that it was possible to perform therapy with
      restitutio ad integrum. This proved that, as opposed to endomyocardial biopsy,
      IMEG diagnosis detected humoral mediated rejection early and with high
      reliability. Furthermore, the immediate recovery in IMEG during therapy indicates
      that the voltage decrease cause by rejection cannot be explained by an
      irreversible loss of myocardium (myocytolysis), but rather may be due to a
      quickly reversible functional impairment.

PMID- 9036699
TI  - [Renaissance of beta blocker therapy in myocardial infarct].
AB  - Beta-adrenergic blocking drugs have been evaluated for the treatment of
      arrhythmias and for the prevention of sudden cardia death, particularly in post
      myocardial infarction patients. Betablockers have been demonstrated to reduce
      mortality, reinfarction, ventricular fibrillation and cardiac rupture in acute
      infarction. Therefore, in patients with suspected myocardial infarction and
      without contraindications, treatment with betablockers should be initiated early
      and continued for at least 2 years. Side-effects are mild and occur in
      approximately 10% of patients. Patients who have contraindications for
      betablockers use early in myocardial infarction should be reevaluated before
      discharge from the hospital and considered for such therapy. Because betablockers
      prevent some of the adverse arrhythmogenic mechanisms seen in chronic heart
      failure, it may be reasonable to expect that these drugs could have a role in
      preventing sudden cardiac death in these patients. Analysis of some of the
      betablocker post-infarction trials indicate that betablockers reduced the risk of
      sudden death in patients with heart failure at baseline. Some studies
      demonstrated also the symptomatic improvement following therapy with betablockers
      in patients with heart failure. But the currently available data are too limited
      to provide conclusive information.

PMID- 9036701
TI  - [Endothelin and big endothelin in coronary heart disease and acute coronary
      syndromes].
AB  - Endothelin (ET), the most potent endogenous vasoconstrictor with mitogenic
      potency, is generated from its precursor big-endothelin (BET) in a proteolytic
      process and discussed as a pathogenetic factor in coronary artery disease and in
      the acute coronary syndromes. Several studies documented elevated plasma
      endothelin concentrations in acute myocardial infarction, but conflicting results
      were reported in patients with stable and unstable angina. Only few studies
      determined big endothelin, although it half-life and plasma concentrations are
      higher in comparison to endothelin. ET and BET levels (Radioimmunoassay,
      Biomedica GmbH, Vienna) were determined in patients with stable angina (SAP, n =
      20), unstable angina (IAP, n = 12), acute myocardial infarction (AMI, n = 12) and
      healthy subjects (NP, n = 11). The concentrations of ET and BET (median (minimum
      maximum) in fmol/ml) of the patients with stable angina (SAP: ET 0.7 (0.3-1.1);
      BET 1.7 (0.7-2.9)), unstable angina (IAP: ET 1.0(0.5-1.7); BET 2.5 (1.3-4.1)) and
      acute myocardial infarction (AMI: ET 1.2 (0.6-2.3); BET 3.6 (3.2-5.3)) showed a
      significant difference compared to controls (NP: ET 0.5 (0.4-0.7); BET 1.4 (1.1
      1.7)) (SAP vs. NP: ET p < 0.01; BET p < 0.05; IAP and AMI vs. NP: ET and BET p <
      0.001). Also, the concentrations of the peptides differed significantly dependent
      on the clinical severity of coronary artery disease (AMI vs. SAP: ET and BET p <
      0.001; AMI vs. IAP: BET p < 0.05; IAP vs. SAP: ET p < 0.05; BET p < 0.01). Twelve
      of 15 patients with big endothelin concentrations over 3 fmol/ml suffered acute
      myocardial infarction. Seven of 12 patients with AMI showed elevated ET and BET
      concentrations before the increase of creatinecinase. There was no correlation
      between number of risk factors per patient, cholesterin and subfractions,
      severity of CAD classified in one-two-three-vessel disease or coronary score
      according to modified criteria of the American Heart Association (AHA). We
      conclude that in patients with coronary artery disease endothelin and big
      endothelin levels are elevated and related to the clinical and not to the
      morphological severity of coronary artery disease. Big endothelin is the more
      sensitive parameter in comparison to endothelin and indicates a severe course of
      myocardial ischemia in patients with unstable angina. The development of assays
      with the possibility of a quick determination of the peptides may be valuable for
      risk stratification of acute coronary events.

PMID- 9036702
TI  - [Sleep apnea as a risk marker in coronary heart disease].
AB  - Obstructive sleep apnea (OSA) and coronary heart disease (CHD) are both frequent
      in the middle ages. Both disease share a similar spectrum or risk factors and
      attendant diseases. The aim of the study was to determine the prevalence of
      obstructive sleep apnea in patients with coronary heart disease diagnosed by
      coronary angiography. Furthermore, influence of sleep apnea and attendant
      diseases and risk factors for coronary heart disease, especially the risk for
      myocardial infarction and reduced left ventricular ejection fraction, was
      investigated. We included in this study 143 patients (121 men, 22 women mean age
      60 +/- 8 years (35-81) who underwent coronary angiography because of angina
      pectoris or were suspicious for CHD due to noninvasive investigations. These
      patients has symptoms of OSA based on a standardized questionnaire. They
      underwent a four-channel screening with a non-laboratory-monitoring-system (NLMS)
      for detection of sleep-related breathing disorders. In addition, spectrum of risk
      factors and concomitant diseases were considered. Sleep apnea was more frequent
      in patients with CHD (30.6%) in comparison to patients without CHD (21.8%), but
      did not reach statistical significance. Patients with CHD and OSA had a
      significantly higher frequency of a history of myocardial infarction and had a
      significantly lower left ventricular ejection fraction than patients without OSA.
      IN CONCLUSION: Patients with the combination of OSA and CHD are at higher risk
      for myocardial infarction and reduced left ventricular ejection fraction.
      Patients with CHD should be screened for OSA in case of secondary prevention.

PMID- 9036703
TI  - [Epidemiology of heart wall rupture in myocardial infarct].
AB  - In a retrospective study including 1888 consecutive patients (pts) with acute
      myocardial infarction (AMI) admitted in the years 1989-1993 to the CCU, the
      relationship between sex, age, history of angina, location of infarction and
      heart wall rupture has been studied in a multivariate regression model. Female
      sex (p = 0.0013), older age (p = 0.0001), first angina during the AMI (p = 0.001)
      were indicative for significantly higher risk of rupture. Women are at higher
      risk only with anterior wall AMI (p = 0.0393). This risk increases continually
      with age, more in pts with inferior wall AMI than anterior wall AMI (p = 0.339).
      Females over the age of 75 with anterior wall AMI and first AP, and males and
      females over 83 with inferior wall AMI and first AP are at the highest risk of
      rupture (48.6% of deaths). We conclude that the defined high risk pts should be
      carefully monitored concerning the signs of impending heart wall rupture.

PMID- 9036704
TI  - [Congenital heart defects in adolescence and adulthood: fatalities and morbidity
      in primary and reoperation].
AB  - Adolescents and adults with congenital heart disease have become a new,
      continuously growing group of patients, because currently improved diagnostics
      and therapy allow the majority of newborns with congenital heart disease to
      survive to adulthood. The objective of this retrospective study was to
      investigate lethality and morbidity after surgery for congenital heart disease in
      adolescents and adults. Between 1989 and 1994, we operated 137 patients (age
      between 15 and 75 years; mean 33.8 +/- 15.1) because of congenital heart disease.
      This was equivalent to 2.7% of all patients, who were operated during this period
      of time. 101 cases were primary operations, in 36 cases (26.3%) a reoperation was
      performed. The most frequent diagnoses were ostium-secundum-defect (37.9%),
      anomalies of the aortic valve including sub- and supravalvular stenoses (9.5%),
      anomalies of the mitral valve (8%), ventricular septal defect (7.3%) and aortic
      coarctation (7.3%). Overall lethality was 5.8%, including emergency cases and all
      late deaths, which have been reported so far. Evaluation of morbidity showed an
      intraoperative cardiac low-output-syndrome in 3.7%, pulmonary failure in 5.8%,
      postoperative renal failure in 4.4% and postoperative bleeding complications in
      7.3% of cases. Mean duration of postoperative ventilation and intensive care
      treatment were 2.3 +/- 5.3 and 3.6 +/- 7.3 d, respectively. In comparison to
      their preoperative status, 71% of patients had improved by one or two NYHA
      classes. We found that the higher perioperative risk related to reoperation had
      no impact on the operation's functional result, as evaluation of postoperative
      functional class showed no difference between primary and re-do cases. The
      general term congenital heart disease describes a very inhomogeneous group of
      patients with a broad spectrum of different diagnoses. The variable morphology
      and pathophysiology of the different congenital heart defects require an
      individual surgical strategy for each patient, in rare cases even the decision
      for a heart- or heart-lung-transplantation. Furthermore, adequate follow-up and
      competent ambulatory treatment of these patients require the cooperation of
      pediatric and adult cardiologists and cardiac surgeons in interdisciplinary
      outpatient clinics.

PMID- 9036705
TI  - [Spiral CT and 3-dimensional reconstruction in evaluation of systemic venous
      obstruction after atrial switch operation for complete transposition of great
      vessels].
AB  - We report findings in spiral-CT from 11 adolescent or adult patients after atrial
      switch operation. The results demonstrate that computed tomography, particularly
      with the use of three-dimensional surface reconstruction, is very useful as a
      highly sensitive procedure for the detailed depiction of residua and sequelae
      after inflow correction for complete transposition. Especially systemic venous
      obstruction (SVO) is a well know complication following Mustard procedure for
      transposition of the great arteries. Demonstration of such obstruction is
      important, since the recognition and quantification of caval obstruction by
      clinical techniques is unreliable and indeed often impossible. Imaging procedures
      such as spiral computed tomography are important for this purpose. Advantages of
      spiral computed tomography, particularly with three-dimensional reconstruction,
      are discussed. The images were compared with findings in echocardiography and/or
      angiography affecting the site of operation.

PMID- 9036706
TI  - [Bilateral acute retrobulbar space-occupying lesion within the scope of
      thrombolytic therapy in myocardial infarct--a case report].
AB  - A 51-year-old male patient with circulatory arrest and ventricular fibrillation
      was brought to the emergency department after restoration of spontaneous
      circulation. ECG presented signs of acute anterolateral myocardial infarction.
      Thrombolytic therapy according to the Neuhaus scheme was initiated. After
      administration of 60 mg rt-PA continuously increasing protrusion and hyposphagma
      of both eyes (left > right) and left-sided monocle-hematoma was observed. CCT
      showed shadowing of sinus ethmoidales frontales, broadening of the left lateral
      rectus muscle and retrobulbar volume increase without any signs of recent
      bleeding. The ophthalmologist had to answer the question if there was, in spite
      of the massive retrobulbar volume increase, a sufficient blood supply for both
      eyes. Ophthalmoscopically there were no signs of intraretinal bleeding or retinal
      ischemia. Intraocular circulation was checked by color Doppler sonography:
      Ophthalmic artery, the short posterior ciliary arteries and central retinal
      artery of both eyes showed very low, but definitely positive bloodflow. Further
      course showed a constant trend towards higher systolic bloodflow velocities in
      all eye vessels, verified by color Doppler sonography. Computer perimetry,
      performed after the recovery of the patient, revealed a visual field defect,
      which was related to a breakdown of the flow in a ciliary artery rather than to
      damage due to compression of the optic nerve. Possible reasons of the retrobulbar
      volume increase under thrombolytic therapy are discussed.

PMID- 9036707
TI  - [Pathogenetic aspects of the L-arginine-NO metabolic pathway in arteriosclerosis
      and possible therapeutic aspects].
AB  - L-arginine is the physiological precursor of nitric oxide (NO) which is formed in
      endothelial cells by the activity of the constitutive NO synthase isoenzyme. NO
      is tonically released from the endothelium, thus maintaining an active
      vasodilator tone and inhibiting platelet aggregation, leukocyte adhesion, and
      vascular smooth muscle cell proliferation. In experimental hypercholesterolemia
      and atherosclerosis as well as in hypercholesterolemic patients, NO-mediated
      responses have been shown to be impaired. Whether decreased formation and/or
      enhanced oxidative inactivation are involved in this process, is still unclear.
      Chronic dietary administration of L-arginine has been shown to exert anti
      atherosclerotic effects in hypercholesterolemic rabbits. Intravenous infusion of
      L-arginine induces NO-dependent peripheral vasodilatation and inhibits platelet
      aggregation in healthy humans as well as in patients with severe limb ischemia
      and generalized atherosclerosis. Whether L-arginine may induce therapeutic
      effects in peripheral vascular disease, still remains unclear.

PMID- 9036708
TI  - [Light-evoked blood flow changes in the posterior cerebral artery].
AB  - In 20 healthy volunteers light evoked changes in blood flow of the posterior
      cerebral artery were studied with color coded Doppler sonography. Doppler flow
      profiles of the PCA were recorded before, during and after exposition with light.
      Under the treatment with light the RI decreased in the mean form 0.61 down to
      0.50, indicating an increase of flow. After redarking the RI increased again up
      to a mean of 0.62. The applied test could be a helpful tool to clarify the
      pathophysiological mechanism in defect seeing.

PMID- 9036709
TI  - [Significance of arterial anastomoses of the distal calf and proximal foot for
      compensation of peripheral arterial occlusive disease].
AB  - The vascular anatomy of the distal calf and proximal foot was studied in 16
      preparations obtained by corrosion. Arterial anastomoses between the different
      vessels are frequently observed and were also detected by digital subtraction
      arteriography in 14 patients with peripheral arterial occlusive disease. The
      comparison between anatomy and arteriography revealed that performed anastomoses
      in the malleolar and proximal foot region are important for compensating crural
      arterial occlusions. The Ramus communicans posterior, the Ramus perforans of the
      fibular artery and the Rete calcaneare play an important role. Whereas in other
      vascular territories collaterals dominate for compensation of occlusions
      performed anastomoses are of crucial importance at the malleolus.

PMID- 9036710
TI  - [Intraoperative quality control after vascular surgery reconstruction of kidney
      and visceral arteries: personal experiences with intraoperative angioscopy].
AB  - Angioscopy was applied as a way of intra-operative assessment after surgical
      reconstruction of renal and visceral arteries in 15 patients. Angioscopy resulted
      in relevant findings, which in part, demanded immediate intra-operative
      consequences. Angioscopy turned out to be a sensitive way of surveillance, the
      findings were easy to interpret.

PMID- 9036711
TI  - [Hereditary hemorrhagic telangiectasia with hepatic involvement and including
      gastric vessels. A case report].
AB  - Hereditary hemorrhagic teleangiectasia (HHT) (Osler-Weber-Rendu-disease) is
      characterized by a combination of muccocutaneous vascular malformations with
      recurrent spontaneous bleeding and a familiar predisposition. Among visceral
      manifestations of this disease are only a few descriptions of hepatic
      involvement. We describe a 53-year-old woman with HHT whose first symptoms of
      hypercirculatory heart failure developed 1.5 years before the final diagnosis of
      HHT. We measured a heart-time-volume of 14-151/min. by echocardiography and a
      flow-volume of 5-9 l/min. in the proper hepatic artery by dopplersonography on
      admission. We were able to demonstrate multiple intra- and extra-hepatic and
      gastric arteriovenous malformations by arteriography. Branches of the proper
      hepatic artery and the left gastric artery were embolized in three serial
      sessions. By this procedure we were able to reduce the flow-volume in the proper
      hepatic artery from 5-9l/min. to 1.5l/min. and the heart-time-volume to a minimum
      of 9.8l/min. and thus stop progression of the hyperdynamic heart failure.

PMID- 9036712
TI  - [Rhythmic lymph extravasation from a lymph fistula].
AB  - A 66-year-old woman with a chronic traumatic lymph fistula is described. Using
      the almost atraumatic fluorescence micro-lymphography the fistula could be
      precisely localized within the ulcer. Lymph flow from deep channels was rhythmic.
      This previously unknown phenomenon of rhythmic retrograde flow in a lymphatic
      fistula is probably due to the activity of contractile segments of lymph
      collectors and an important factor for the non-healing of ulcers.

PMID- 9036713
TI  - [Therapy of renovascular hypertension in neurofibromatosis: surgical
      revascularization versus percutaneous transluminal angioplasty].
AB  - Vasculopathy is a rare and undervalued complication in neurofibromatosis.
      Histopathological changes of the vascular wall may lead to relevant renal artery
      stenosis. We report a case of a 17-year-old patient with neurofibromatosis and
      severe renovascular hypertension resulting from a proximal renal artery stenosis.
      Attempted percutaneous renal angioplasty was unsuccessful and the patient was
      referred for operative revascularization. After insertion of an aortorenal bypass
      with a reversed saphenous vein graft the patient became normotensive without
      medication. Based on our own experience and a review of the literature we
      recommend operative reconstruction of stenotic renal arteries in
      neurofibromatosis.

PMID- 9036714
TI  - [Sudden cardiac death in giant cell arteritis].
AB  - The autopsy findings of a 74-year-old women who unexpectedly died are presented.
      She had suffered from polymyalgia but typical symptoms of temporal arteritis had
      been absent and tentative treatment with prednisone had not improved the
      polymyalgic pain. The autopsy revealed a generalized giant cell arteritis
      involving the left temporal artery, the left common carotid artery, the ascending
      aorta, a submucosal artery of the ileum and the left anterior descending branch
      of the coronary arteries. Histology showed typical granulomatous infiltrates
      including giant cells, followed by thrombotical occlusion of the coronary artery
      branch and subsequent myocardial infarction. Giant cell arteritis is a systemic
      vasculitis of aged subjects with predominant localisation in the cranial
      arteries, but occasional involvement of any type of visceral and peripheral
      arteries. Coronary involvement with sudden cardiac death is not a commen
      complication of giant cell arteritis but has occasionally been described in the
      literature.

PMID- 9036715
TI  - [The time for gold therapy has not yet expired].

PMID- 9036716
TI  - [Mechanism of action of gold in treatment of rheumatoid arthritis].
AB  - Gold is one of the oldest and most effective drugs in the treatment of rheumatoid
      arthritis. Gold unfolds its therapeutic efficacy through various influences on
      the immune system. Gold alters antigen-processing and reduces cytokine expression
      of macrophages. Additionally, gold reduces adhesion molecules, antibody
      production and inhibits proteolytic enzymes. However, macrophages also oxidize
      gold(I) to gold(III) which is - by its increased protein reactivity - responsible
      for a large part of the gold side-effects.

PMID- 9036717
TI  - [Does parenteral gold inhibit roentgen progression of chronic polyarthritis?].
AB  - The retardation of radiological progression is one of the most important
      characteristics of a disease-modifying effect of an antirheumatic drug. For the
      following overview 10 trials were identified dealing with x-ray progression under
      treatment with parenteral gold. Nine of these trials were randomised parallel
      studies, one was a retrospective long-term observational study, all had a control
      group, in five this control group was treated with placebo, in two trials
      parenteral gold was compared with another DMARD (auranofin and methotrexate,
      respectively), in two trials different doses of gold were compared and in two
      trials the radiological progression during the first 6 months was compared with
      the following treatment period (in one of these trials gold was compared with
      methotrexate as well). The duration of treatment and follow-up was up to 1 year
      in two trials, up to 2 years in six, and over 2 years in only two studies. There
      is a great number of limitations in these studies: for instance, there was a
      large number of withdrawals who were not followed, x-rays were available for
      evaluation only in a relatively small proportion of treated patients in five
      studies, in six studies the disease duration was over 2 years at baseline, which
      limits the evaluability of x-ray progression for technical reasons. In one study
      juxta articular osteoporosis and joint swelling were evaluated; but these
      parameters are very difficult to evaluate in a multicenter study because of the
      different quality of the films. In spite of all limitations and reservations with
      the studies reviewed the published results indicate a reduction of radiological
      progression with parenteral gold treatment of rheumatoid arthritis patients: in
      the placebo-controlled studies outcome in the gold group was significantly better
      than in the placebo group. The study of the Empire Rheumatism Council failed to
      show a significant difference compared to the control group after 30 months, but
      the patients had been treated sufficiently only for 5 months. The study of Cats
      indicated a better outcome in the group of patients with a high gold dose, which
      is confirmed by the retrospective analysis of Luukkainen. In a comparison between
      113 patients treated with parenteral gold and 119 patients treated with auranofin
      for 1 year Larsen found a significantly smaller progression in the patients
      treated with parenteral gold. In a patient population of 73 and 53 the difference
      between methotrexate and parenteral gold was too small to be detectable, but the
      progression curve was significantly flattened after the first 6 months,
      indicating a treatment effect. In a macroradiographic study the erosion surface
      area increased during the first 6 months of gold treatment, it did not change
      during the second 6 months, and decreased during the third 6 months together with
      healing of erosions. In conclusion, the studies reviewed in this paper indicate a
      disease-modifying potency of parenteral gold treatment, especially when the
      treatment is started early and sufficiently dosed.

PMID- 9036718
TI  - [Nosologic criteria in rheumatology].
AB  - Nosologic criteria are important tools for diagnosis and categorization of
      rheumatic diseases, disease status and outcome. They have been developed
      predominantly for phenomenologic syndromes (of unknown etiology) and are
      standards of the scientific communication as well as necessary instruments for
      the selection of patient groups for investigations in different fields of
      rheumatology (epidemiology, etiology, pathogenesis, clinical rheumatology,
      diagnostics, therapy). Diagnostic criteria help to identify disease in individual
      patients. Classification criteria separate patients with a particular disease
      from patients without the disease and are useful to select and describe patient
      groups. Status indices assess disease activity and actual damage according to
      reversible or irreversible features respectively. Prognostic criteria
      differentiate patients with probably favorable or severe disease course or
      outcome, and outcome criteria are designed to assess the overall impact of a
      disease as dependent variables for clinical studies. This review describes the
      different types and purposes of nosological criteria in different rheumatic
      diseases as well as their problems. Some aspects of the actually used criteria
      especially from the "Diagnostic and Therapeutic Criteria Committee" of the
      American College of Rheumatology are critically commented.

PMID- 9036719
TI  - [Lumbo-sacroiliac hyperostosis with retroperitoneal fibrosis in spondarthritis
      hyperostotical pustulo-psoriatica--with sternocostoclavicular hyperostosis and
      superior and inferior venous obstruction syndrome: pathogenetic hypothesis of
      fibro-osteopathia psoriatica].
AB  - We report two cases of retroperitoneal fibrosis which were found in 38 patients
      with "spondarthritis hyperostotica pustulo-psoriatica" (spond.hyp.p.-p.).
      Spond.hyp.p.-p. is associated with sternocosto-clavicular hyperostosis and
      resembles pustulotic arthroosteitis and SAPHO syndrome. However, as
      dermatologically and osteo-histopathologically documented, it is an
      enthesiopathic and hyperostotic form of spondarthritis psoriatica. Both cases
      show a lumbosacroiliac hyperostosis (LSIH) which is a rare analogue to
      sternocosto-clavicular hyperostosis (SCCH). Facultative paraosseous connective
      tissue proliferation results in a new form of retroperitoneal fibrosis with
      sacroiliac origin. Mediastinal and pelvic masses cause superior and inferior vena
      caval obstruction syndromes. Because of proven psoriasis in pelvic bone with para
      periostal

PMID- 9036720
TI  - [Gold antirheumatic drug: desired and adverse effects of Au(I) and Au(III)
      [corrected] on the immune system.
AB  - Three new findings are reviewed that help to understand the mechanisms of action
      of anti-rheumatic gold drugs, such as disodium aurothiomalate (Na2Au(I)TM): i) We
      found that Na2Au(I)TM selectively inhibits T-cell receptor-mediated antigen
      recognition by murine CD4+ T-cell hybridomas specific for antigenic peptides
      containing at least two cysteine residues. Presumably, Au(I) acts as a chelating
      agent forming linear complexes (Cys-Au(I)-Cys) which prevents correct antigen
      processing and/or peptide recognition by the T-cell receptor, ii) We were able to
      show that Au(I) is oxidized to Au(III) in mononuclear phagocytes, such as
      macrophages. Because Au(III) rapidly oxidizes protein and itself is re-reduced to
      Au(I), this may introduce an Au(I)/Au(III) redox system into phagocytes which
      scavenges reactive oxygen species, such as hypochlorous acid (HOCl) and
      inactivates lysosomal enzymes, iii) Pretreatment with Au(III) of a model protein
      antigen, bovine ribonuclease A (RNase A), induced novel antigenic determinants
      recognized by CD4+ T lymphocytes. Analysis of the fine specificity of these
      "Au(III)-specific" T-cells revealed that they react to RNase peptides that are
      not presented to T-cells when the native protein, i.e., not treated with Au(III),
      is used as antigen. The T-cell recognition of these cryptic peptides did not
      require the presence of gold. This finding has important implications for
      understanding the pathogenesis of allergic and autoimmune responses induced by
      gold drugs. Taken together, our findings indicate that Au(I) and Au(III) each
      exert specific effects on several distinct functions of macrophages and the
      activation of T-cells. These effects may explain both the desired anti
      inflammatory and the adverse effects of antirheumatic gold drugs.

PMID- 9036721
TI  - [Low dose methotrexate therapy in chronic polyarthritis--an update].
AB  - Since the early eighties methotrexate (MTX) has become of increasing importance
      in long-term therapy of rheumatoid arthritis (RA) as a disease modifying drug
      (DMARD). Nowadays it is probably the most frequently prescribed DMARD for RA and
      can be regarded as the gold standard in long-term therapy. MTX can be
      administered orally or parenterally, the bioavailability shows high individual
      differences, but is about 70% after oral administration on average. Its protein
      binding amounts to 50%, the main pathway of elimination is renal tubular
      secretion, to a smaller extent also biliary excretion. MTX polyglutamates are
      stored intracellularly. Its mode of action in RA is not completely elucidadet
      yet, besides inhibition of dihydrofolatereductase and consequently inhibition of
      thymidilate synthesis, some antiinflammatory effects, such as stimulation of
      Adenosine release from neutrophils, may contribute to the therapeutical effects.
      MTX' efficacy could be proven by several controlled trials, some of them lasting
      for more than five years. During long-term therapy with MTX a folate deficiency
      may occur, which can lead to some side effects. Most important but rarely
      occurring is pneumonitis, moreover hepatotoxicity and hematological features have
      to be intensively considered. The risk of the development of osteopenia or an
      increased incidence of malignancies during MTX therapy is currently investigated.
      In case of clinical and laboratory controls at regular intervals and patient
      education MTX therapy can be regarded as effective, well tolerable and
      considerably safe for patients with rheumatoid arthritis.

PMID- 9036723
TI  - [Hormonal status of the woman and its effect on symptoms and progression of
      chronic polyarthritis].
AB  - In a retrospective study 434 female patients suffering from rheumatoid arthritis
      (mean age at the onset of disease 45.7 +/- 13.3 years) were asked about
      information concerning number of deliveries, abortions, hormonal contraception or
      treatment respectively, and any changes of complaints during pregnancy, after
      deliveries or hormonal treatment. The effect of oral contraceptives on the
      progression of the disease was of particular interest. The present results show
      that the progression of RA is not influenced dramatically by the hormonal
      situation or hormonal treatment respectively. The worldwide opinion of female sex
      hormones regarding their influence on symptoms and progression of RA and the risk
      of developing RA are controversial. Positive and negative studies on the
      influence of hormonal situation or treatment respectively are depending very much
      on the individual study conditions. In order to find out more on the effects of
      hormones on RA, a prospective approach and much more data would be required. This
      is the reason why no study so far has shown unanimously acceptable results.

PMID- 9036722
TI  - [Possible effect of hormones on immune and inflammatory processes in female
      patients with chronic polyarthritis].
AB  - The influence of gender on the prevalence of rheumatoid arthritis (RA) is well
      known. We examined 40 female patients with RA to show the possible influence of
      androgen hormones on inflammation and immune system. We measured blood count,
      blood sedimentation rate, C-reactive protein routinely and free and bound
      testosterone, dehydroepiandrosterone-sulfate (DHEA-S), prolactin, insulin like
      growth factor-1 (IGF), IgA-rheumatoid factor (IgA-RF) and the monocyte marker CD
      14 of radioimmunoassays and enzymeimmunoassays. The female patients with RA had
      lower androgen levels correlating with higher inflammatory markers which are not
      rising significantly with higher age. The significantly raised IgA-RF with
      abnormal low testosterone levels points out a poor prognosis for developing joint
      erosions. The simultaneously reduced levels of prolactin may be rather caused by
      cytokines and could have additional connections to the anemia in RA. Somatomedin
      correlated inversely to the degree of inflammation, measured by BSR, CRP and CD
      14, a fact which could indicate a reduced, Somatomedin-induced, synthesis in
      matrix and collagen of cartilage in "active" RA. The results point to the
      existence of a reciprocal connection of the endocrine system with the immune
      system.

PMID- 9036724
TI  - [Aggressive therapy of highly active systemic lupus erythematosus].
AB  - Life-threatening exacerbations of systemic lupus erythematosus can endanger the
      function of vital organ systems and require massive immunosuppressive treatment
      after the diagnostic delineation of the situation. In addition to high dosages of
      corticosteroids, the introduction of high dose intravenous cyclophosphamide has
      improved the prognosis of organ function in SLE in the past years. The concept of
      plasmapheresis has been left in most centers, although in vitally dangerous
      situations the application of selective immunoglobulin removal techniques
      (immunoabsorption) has been reported to be beneficial. The long-term treatment
      following the acute exacerbations has to consider the side effects of all
      immunosuppressive drugs like infections and neoplasia, although the danger of
      another autoaggressive attack of the patient's own immune system has to be kept
      in mind.

PMID- 9036725
TI  - [Correlation between molecular parameters of hyaluronic acid and viscoelasticity
      of synovia].
AB  - The viscoelastic properties of hyaluronic acid solutions and synovial fluids were
      investigated by oscillating capillary rheology in a frequency range from 0.03 to
      30 Hz. A clear dependency of these parameters, especially of the elastic
      component, on the molecular weight of the hyaluronic acid molecules was obtained.
      The addition of hyaluronic acid solutions to pathological synovial fluids
      improves the viscoelastic parameters depending on the applied dose. However, the
      rheological behavior of a "healthy synovial fluid" could not be reached by the
      procedure.

PMID- 9036726
TI  - [Evaluation of 2 questionnaires with reference to their suitability for self
      evaluation of patients with gonarthrosis. A contribution to quality assurance in
      rheumatology].
AB  - Questionnaires are useful instruments to evaluate disability and handicap in
      patients suffering from rheumatic diseases. Most of the used questionnaires
      require a time consuming interview with the attending physician or medical health
      personnel. Two (Larson and Lequesne) well established questionnaires are
      available for osteoarthritis(OA)-patients. Since it would be desirable to have
      reliable patients self reporting questionnaires, we have tested the utility and
      validity of these questionnaires by comparing the results of patients self
      reports with the results obtained by medical health personnel (4 occupational-
      and physiotherapists) in the same patients (n = 52). The analysis of the
      questionnaires revealed that results obtained by the Larson technique gave very
      different (p < 0.01) global and detail scores as assessed by patients or medical
      staff. This difference of assessments was not influenced by the stage of
      arthrosis as defined by x-ray. The Lequesne questionnaires gave essentially
      similar results, with a significant difference between assessment of disease
      severity by patients in comparison to results obtained by medical staff. The
      results obtained by the 4 members of the medical staff did not differ
      significantly from each other. From our study it is concluded that neither the
      Larson nor the Lequesne questionnaire can be recommended for scientific use as a
      reliable patients self reporting evaluation of disease severity in
      osteoarthritis.

PMID- 9036727
TI  - [Effect of inpatient rehabilitation measures on patients with total hip
      endoprostheses--evaluation 15 months after operation].
AB  - 159 patients were examined approximately 15 months after hip arthroplasty. 116 of
      these patients have had at that time point a postoperative 4 week hospital stay
      for rehabilitation. A score that considered pain at motion and at rest, maximal
      walking capacity and activity of daily living was used for evaluation. The
      preoperative conditions did not differ between patients that had their
      postoperative hospital stay for rehabilitation (n = 116) and those that did not
      (n = 43). The results at the time of examination were regarded as excellent
      (group 1; score 3) in 64 (40.3%) patients, as good (group 2; score 4) in 56
      (35.2%) patients and as poor (group 3; score > or = 5) in 39 (24.5%) patients.
      The amount of patients with a hospital stay for rehabilitation was significantly
      (p = 0.025) higher in the patient groups with excellent or good results in
      comparison with the patients with poor postoperative outcome. The most excellent
      results were obtained in patients who had their rehabilitation within the first
      two months after surgery (p = 0.008). Apart from the above mentioned score the
      following-additionally assessed-parameters differed significantly between the 3
      groups: hip mobility; pain elicited by pressure on the operated joint; pain in
      the contralateral hip or knee joints; consumption of analgetics; walking time for
      15 meters; degree of handicap as assessed by the patient or the occupational
      therapist or the physician; coping with household activities (for females only).
      We conclude that a poor result of hip arthroplasty may be due not only to
      degenerative joint disease of the lower limbs but also (or in combination) to the
      lack of a postoperative hospital stay for rehabilitation.

PMID- 9036728
TI  - Annual meeting of the Norwegian Neurological Society. Oslo, Norway, November
      1995. Abstracts.

PMID- 9036729
TI  - [Anterior instability of the shoulder in athletes: apropos of 51 cases of
      stabilization using the Latarjet-Patte intervention].
AB  - We report the 45-month results of the Bristow Latarjet procedure in 48 patients
      (51 shoulders), all sportsmen. At review, 87% were satisfied, 71% practiced the
      same sport at the same level, and 74% had good or excellent objective results.
      Five patients reported recurrence of dislocation, external rotation was
      restricted more than 10 degrees in 36%, and 31% of the shoulders had radiological
      evidence of degenerative arthropathy. We compare the results with the literature,
      particularly concerning recurrent dislocation and osteoarthritis.

PMID- 9036730
TI  - [Labeled leukocyte scintigraphy and total hip prosthesis].
AB  - During the last few years, labelled leukocyte scintigraphy has become a decisive
      tool in the diagnosis of bone infections. However, this test may sometimes be
      deceptive as far as hip prostheses are concerned. The authors have carried out a
      retrospective study of 62 labelled leucocyte scintigraphies performed for
      suspected infection of a hip prosthesis. The comparison of the results with the
      different clinical, biological and radiological factors and the follow up of the
      patients allows determination of the sensitivity and specificity of this test
      which are 41% and 100% respectively. The results reported in the literature and
      the indications for this examination are discussed.

PMID- 9036731
TI  - [Transient osteoporosis of the hip and magnetic nuclear resonance].
AB  - The authors evaluated the diagnostic importance of MRI in a woman who presented
      with transient osteoporosis of both hips, over an interval of three years. The
      diagnosis was made only during the second episode with the aid of MRI. The
      patient recovered without sequelae.

PMID- 9036732
TI  - [Astragalocalcanean subluxation in children].
AB  - The authors report a unique case of talo-calcaneal subluxation in a child
      following minor trauma. The reduction proved to be straightforward, and the
      outcome was entirely favorable.

PMID- 9036733
TI  - [Synovial cyst of the hip: a rare cause of iliac vein compression].
AB  - A case of synovial cyst of the hip presenting as a venous compression in the
      lower limb is reported. From a review of about 100 cases reported in the
      literature, the pathogenesis, diagnosis and treatment are discussed.

PMID- 9036734
TI  - [Possible role of viral agents in the pathogenesis of squamous cell carcinomas of
      the head and neck].

PMID- 9036735
TI  - [Oncogenes and tumor suppressor genes: general features].

PMID- 9036736
TI  - [Oncogenes and tumor suppressor genes in head and neck squamous cell carcinomas].

PMID- 9036737
TI  - [The DNA ploidy in squamous cell carcinomas of the head and neck with particular
      reference to prognosis].

PMID- 9036738
TI  - [Oncogenes and oncosuppressor role in head and neck carcinomas].

PMID- 9036739
TI  - [Epidemiology of cancers of the upper digestive and respiratory tract].

PMID- 9036740
TI  - Circadian variation in the onset of unstable angina and non-Q-wave acute
      myocardial infarction (the TIMI III Registry and TIMI IIIB).
AB  - Circadian variation has been demonstrated in several types of acute
      cardiovascular disease, including acute myocardial infarction (AMI), sudden
      cardiac death, silent ambulatory ischemia, and thrombotic stroke. In contrast, no
      diurnal variation was observed in 1 study of non-Q-wave AMI, and limited data are
      available for unstable angina. To assess whether circadian variation is present
      in unstable angina and non-Q-wave AMI, we examined the time of onset of ischemic
      pain in 7,731 patients who were prospectively identified in the Thrombolysis in
      Myocardial Ischemia (TIMI) III Registry, 3,318 of whom were enrolled in the
      prospective study, and in 1,473 patients enrolled in the TIMI IIIB trial. A
      circadian variation in the onset of pain was observed, with an increase in the
      number of patients experiencing the onset of pain in the morning hours between 6
      A.M. and 12 noon (p <0.001). This circadian variation was observed both in
      patients with unstable angina and in those with evolving non-Q-wave AMI. A
      similar circadian pattern was observed in all subgroups tested. These findings
      were confirmed in the TIMI IIIB trial and complement previous studies suggesting
      that circadian variation exists in the onset of the full spectrum of myocardial
      ischemic syndromes.

PMID- 9036741
TI  - Comparison of heparin therapy for < or = 48 hours to > 48 hours in unstable
      angina pectoris.
AB  - Of 450 consecutive patients with unstable angina admitted to a tertiary care,
      university-based medical center over a 24-month period, 334 were administered
      heparin and aspirin for some length of time. Two groups of 98 patients matched
      for acuity and gender at baseline were treated with either < or = 48 hours (group
      1) or > 48 hours (group 2) of heparin. The acuity model used in this study
      incorporates 6 factors: age, recent myocardial infarction, treatment with
      intravenous nitroglycerin, previous therapy with beta blockers or calcium
      antagonists, baseline ST depression, and diabetes. Despite similar risks and
      overall clinical outcome, group 2 had significantly more myocardial infarction or
      death after 48 hours than group 1 (p = 0.01). In part, this was due to a delay in
      the performance of coronary angiography (2.8 +/- 1.4 vs 3.5 +/- 15 days, p =
      0.01), coronary intervention (2.7 +/- 1.8 vs 5.1 +/- 2.3 days, p = 0.01), and
      bypass surgery (3.8 +/- 3.6 vs 7.0 +/- 5.6 days, p = 0.02). There was no
      difference between groups regarding the success of coronary intervention (90% vs
      88%, p = NS). Heparin duration was influenced by the finding of intracoronary
      thrombus or ulceration on angiography before revascularization, as each finding
      was seen more often in group 2 (thrombus, 12% vs 24%; ulceration, 38% vs 60%).
      These results suggest that the optimal duration of heparin therapy is up to 48
      hours after admission in unstable angina; a longer time period is associated with
      increased adverse consequences.

PMID- 9036742
TI  - Primary angioplasty versus thrombolysis in the treatment of acute myocardial
      infarction. ALKK Study Group.
AB  - This study investigates the hypothesis if primary angioplasty is superior to
      intravenous thrombolysis in the treatment of acute myocardial infarction (AMI).
      Small prospective randomized studies did not demonstrate a significant benefit
      regarding total mortality. A total of 14,980 patients with AMI were registered by
      "The 60-Minutes Myocardial Infarction Project," a prospective multicenter
      observational study: 210 of these patients were treated with primary angioplasty.
      A matched pair analysis comparing 1 primary angioplasty patient with 3
      intravenous thrombolysis patients could be performed in 156 primary angioplasty
      patients. Criteria for matching were age, sex, location of AMI, systolic blood
      pressure, previous AMI, and prehospital delay. Patients with a bundle branch
      block or requiring resuscitation were excluded from analysis. Because of
      matching, both groups showed similar baseline characteristics. Patients with
      primary angioplasty had more relative contraindications for thrombolysis (ulcers:
      10.3% vs 2.3%, recent intramuscular injections: 6.4% vs 1.6%, recent surgical
      interventions: 5.1% vs 1.1%, central punctures: 9% vs 3.9%). There was a tendency
      toward less combined adverse events in the primary angioplasty group (3.2% vs
      5.7%, odds ratio [OR] = 0.55, 95% confidence interval [CI] = 0.21 to 1.44). In
      hospital mortality rates in the primary angioplasty group and thrombolysis group
      were 4.3% and 10.3%, respectively (OR = 0.39, 95% CI = 0.17 to 0.92). The
      difference in mortality could already be demonstrated within the first 48 hours
      with 1.9% versus 5.3% deaths (OR = 0.35, 95% CI = 0.11 to 1.14). Thus this study
      indicates a superiority of primary angioplasty in comparison to intravenous
      thrombolysis in AMI even in a clinical routine setting, with a reduction of
      hospital mortality of about 60%.

PMID- 9036743
TI  - Predicting adverse outcome with exercise SPECT technetium-99m sestamibi imaging
      in patients with suspected or known coronary artery disease.
AB  - The goal of this study was to determine the ability of exercise single-photon
      emission computed tomographic (SPECT) technetium-99m (Tc-99m) sestamibi imaging
      to predict adverse events in a population with a comparable distribution of men
      (n = 114) and women (n = 115). Consecutive patients referred for evaluation of
      chest pain syndrome, known coronary artery disease, or residual ischemia after
      acute myocardial infarction underwent imaging using a single-headed SPECT camera.
      Clinical readings were reviewed and scored by independent observers as normal or
      abnormal. Follow-up, defined as time from scanning until an event, late
      revascularization, or patient response averaged 19.2 +/- 5.2 months and was 90%
      complete (229 of 255 patients). Cardiac death and nonfatal infarction were
      corroborated by chart review or physician contact. Patients were excluded from
      analysis if a revascularization procedure was performed within 1 month of
      imaging. There were 172 patients with normal scans (67%) and 83 with abnormal
      scans (33%). Of the patients in whom followup was obtained, 2 of 155 with normal
      scans (0.8%/year) and 6 of 74 with abnormal scans (5.4%/year) had cardiac events.
      Statistical analysis using the Kaplan-Meier survival curves suggests a
      significant difference in event-free survival between normal and abnormal scans.
      Patients with abnormal scans portended a worse outcome (chi-square = 8.04, p
      <0.005). Thus, exercise SPECT Tc-99m sestamibi scintigraphy is useful for
      prognostication in a mixed population of patients with suspected or known
      coronary artery disease in which women comprised 50% of the patient cohort.

PMID- 9036744
TI  - The impact of optimal stenting techniques on cardiac catheterization laboratory
      resource utilization and costs.
AB  - Coronary stenting has been shown to reduce angiographic restenosis and improve
      clinical outcomes compared with conventional balloon angioplasty, but at greater
      in-lab cost. Recent studies have suggested that "optimal" stent deployment can
      eliminate the need for intensive oral anticoagulation after stenting, with the
      potential to reduce vascular complications, length of stay, and hospital cost.
      Between January and June 1995, we performed elective 1-vessel coronary stenting
      in 78 patients with a single, discrete (< 15 mm) coronary stenosis (optimal
      single-lesion group) and in 30 patients with either a single, long stenosis or
      serial discrete lesions (optimal multilesion group). Compared with stent patients
      from the Stent Restenosis Study (STRESS) economic substudy, optimal single-lesion
      stenting required more stents (1.3 +/- 0.6 vs 1.1 +/- 0.4, p <0.01) and more
      adjunctive angioplasty balloons per patient (2.5 +/- 1.0 vs 2.0 +/- 0.9, p
      <0.01). As a result, catheterization laboratory costs for single-lesion stenting
      increased by nearly $600 between 1993 and 1995 ($4,619 +/- $1,120 [median $4,435]
      to $5,209 +/- $1,697 [median $4,6731, p <0.01). Compared with the STRESS
      angioplasty group, optimal coronary stenting increased catheterization laboratory
      costs by nearly $2,200 ($3,012 +/- $1,382 [median $2,548] vs $5,209 +/- $1,697
      [median $4,673], p <0.01). Optimal stenting of long lesions or multiple discrete
      stenoses increased catheterization laboratory costs by an additional $2,000
      compared with optimal single-lesion stenting ($7,201 +/- $2,428 [median $6,887]
      vs $5,209 +/- $1,697 [median $4,673], p <0.01). These findings demonstrate that
      optimal coronary stenting increases in-lab procedural resource utilization and
      costs compared with historical stenting techniques. Based on the downstream cost
      savings seen in the STRESS trial ($1,400/patient), it is unlikely that current
      optimal stenting techniques will result in an overall cost savings compared with
      balloon angioplasty.

PMID- 9036745
TI  - Compliance and efficacy of cardiac rehabilitation and risk factor modification in
      the medically indigent.
AB  - To compare the compliance and efficacy of cardiac rehabilitation in medically
      indigent patients with more affluent patients, we evaluated the first 65 patients
      referred to a new cardiac rehabilitation program of whom 36 were medically
      indigent (i.e., dependent on Medicaid for health care reimbursement) and 29 were
      funded by private medical insurance. Attendance during 12 weeks of monitored,
      supervised, phase II cardiac rehabilitation was examined retrospectively. In
      addition, training history, cardiovascular response to submaximal exercise,
      dietary fat intake, and smoking incidence were studied at baseline and repeated
      prospectively between 6 months and 1 year (8.2 +/- 1.1 months) after program
      completion. Both the indigent and private patients attended >90% of scheduled
      sessions and achieved a significant improvement in submaximal work capacity which
      was well maintained at the time of follow-up. Also, both groups continued to eat
      a diet low in saturated and total fat. The indigent patients smoked more before
      the program but were equally successful at quitting cigarette smoking as the
      private patients. We conclude that in the appropriate setting, indigent patients
      can successfully complete and maintain excellent compliance with a program of
      coronary risk factor modification including exercise training, dietary
      modification, and cessation of cigarette smoking, to a degree equivalent to more
      affluent and educated patients. Compliance may be enhanced by employing a small
      program emphasizing extensive personal contact with rehabilitation staff.

PMID- 9036746
TI  - Standard versus low-dose weight-adjusted heparin in patients treated with the
      platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 Fab)
      during percutaneous coronary revascularization. PROLOG Investigators.
AB  - Blockade of the platelet glycoprotein IIb/IIIa receptor by abciximab (c7E3 Fab)
      during coronary intervention reduces the incidence of ischemic complications, but
      has been associated with a doubling of the risk for bleeding complications. The
      present pilot study investigated whether modification of heparin dosing and/or
      early sheath removal would reduce the hemorrhagic complications associated with
      abciximab. One hundred three patients undergoing coronary intervention received
      abciximab (0.25 mg/kg bolus, 10 microg/min infusion for 12 hours) and aspirin and
      were randomized by a 2 x 2 factorial design to 1 of 2 weight-adjusted heparin
      doses and to 1 of 2 strategies for heparin discontinuation and vascular sheath
      removal. In the "standard-dose heparin" group, an initial bolus of 100 U/kg was
      administered to achieve a procedural activated clotting time (ACT) > or = 300
      seconds; in the "low-dose heparin" group, an initial bolus of 70 U/kg was
      administered without adjustment for ACT. In the "late sheath removal" arm,
      heparin infusion was continued for the 12-hour duration of abciximab infusion,
      followed by sheath removal; in the "early sheath removal" group, heparin was
      stopped after the interventional procedure and sheaths were removed during the
      abciximab infusion. There were no apparent differences between patients
      randomized to the different treatment groups with regard to the occurrence of
      ischemic end points. Rates of bleeding and blood transfusion were reduced by low
      dose heparin and early sheath removal and were lowest when both strategies were
      combined. Reduction and weight adjustment of heparin dose and early sheath
      removal in the setting of platelet inhibition with abciximab during coronary
      intervention may be useful in diminishing the incidence of hemorrhagic
      complications without loss of clinical efficacy.

PMID- 9036747
TI  - Echocardiographic prediction of complications in patients with chest pain.
AB  - The optimal role of Doppler echocardiography in the evaluation of patients with
      acute chest pain syndromes is unclear. We prospectively studied a cohort of 466
      patients admitted with acute chest pain syndromes to clarify the relation between
      echocardiographic data and the risk of serious predischarge complications, and to
      determine if echocardiographic data can provide incremental prognostic
      information beyond clinical and electrocardiographic variables. Doppler
      echocardiograms, performed an average of 21 hours after presentation, were
      independently analyzed by 2 echocardiographers for information on global left and
      right ventricular function and valvular disease. Regional function was assessed
      by a wall motion index (WMI). A composite complications end point was positive if
      significant recurrent myocardial ischemia, heart failure, or arrhythmia developed
      after the echocardiogram. In univariate analysis, left (odds ratio [OR] 2.9, 95%
      confidence interval [CI] 1.6, 5.1) and right (OR 2.7, 95% CI 1.2, 6.2)
      ventricular function, left ventricular end-diastolic (OR 1.6/cm, 95% CI 1.1, 2.3)
      and end-systolic (OR 1.4/cm, 95% CI 1.1, 1.9) dimensions, and WMI (OR 3.0, 95% CI
      1.8, 4.8) predicted complications that developed after the echocardiogram. In
      multivariate analysis, WMI remained an incremental predictor of risk with an OR
      of 2.2/unit (95% CI 1.2, 3.9) scaled from 1 to 4. Even in the subset of 403
      patients without acute myocardial infarction, WMI was associated with an OR of
      1.9 (95% CI 1.0, 3.7). We conclude that early echocardiography provides
      incremental prognostic information concerning risk of subsequent complications in
      patients hospitalized with chest pain.

PMID- 9036748
TI  - Morbidity and use of medical resources in patients with chest pain and normal or
      near-normal coronary arteries.
AB  - To evaluate morbidity and use of medical resources in patients with chest pain
      and normal or near-normal coronary angiograms: 2,639 consecutive patients who
      underwent coronary angiograms due to chest pain were registered. Two years
      thereafter all patients who showed normal or near-normal coronary angiograms were
      approached with a questionnaire regarding hospitalization during the last 4 years
      (2 years before and 2 years after angiography). All medical files were also
      examined. Of the patients who underwent angiography, 163 (6%) had no significant
      stenoses, and of these, 113 showed complete normal angiograms and 50 showed mild
      (i.e. <50%) stenoses. During the 2 years before diagnostic angiogram, 66% of the
      patients were hospitalized compared with only 35% during 2 years after
      angiography (p <0.001). The reduction in hospitalization was due to curtailed
      utilization of medical resources for cardiac reasons; mean days in hospital was
      6.6 days before angiography versus 2.8 days after (p <0.001). There were no
      significant differences in hospitalization when comparing patients with mild
      stenoses and completely normal angiograms. There were, furthermore, no
      differences between patients with positive or negative exercise tests. Thus, the
      need for hospitalization is significantly reduced after a diagnostic angiogram
      reveals normal or near-normal coronary arteries.

PMID- 9036749
TI  - Comparison of patients with either < 70% diameter narrowing or > or = 70%
      narrowing of the right coronary artery when performing rotational atherectomy on
      > or = 1 narrowing in the left coronary arteries.
AB  - This study compares the complication rates of patients undergoing rotational
      atherectomy of the left coronary system who had either minimal or significant
      narrowing of the right coronary artery (RCA). A series of 1,872 patients from a
      multicenter registry who were treated for left coronary artery disease were
      divided into <70% diameter stenosis (mild) and > or = 70% stenosis (severe) of
      the RCA. The patient demographics, lesion characteristics, and frequency of
      procedural complications for each group were compared. Of the 1,872 patients
      undergoing rotational atherectomy of the left coronary system, 86.3% (n = 1,616)
      had mild RCA disease and 13.7% (n = 256) had severe RCA disease. Comparing the
      mild and severe groups, death (0.8% vs 3.1%, p <0.005), non-Q-wave myocardial
      infarction (5.1% vs 8.6%, p <0.04), and bypass surgery (2.7% vs 5.8%, p <0.02)
      were increased in the severe group. Within the severe group, 7 of 8 deaths were
      in the 128 patients with total occlusion of the RCA. Multivariate analysis
      demonstrated that RCA stenosis increases the risk of death by 4.9, bypass surgery
      by 2.6, and non-Q-wave myocardial infarction by 1.8. Patients treated for left
      coronary disease who have > or = 70% stenosis of the RCA have increased
      complications during rotational atherectomy.

PMID- 9036750
TI  - Predictors for successful ablation of right- and left-sided idiopathic
      ventricular tachycardia.
AB  - This study reports on predictors for successful radiofrequency (RF) ablation of
      idiopathic ventricular tachycardia (VT) in 48 patients--35 with right ventricular
      (RV) outflow tract and 13 with left ventricular VT. In RV outflow tract
      idiopathic VT, RF ablation was successful in 29 of 35 patients (83%). The
      following information allowed differentiation between patients with and without a
      successful RF ablation: > 1 induced VT morphology (O vs 3); presence of delta
      wave-like beginning of the QRS (2 vs 3) and > or = 11 of 12 leads showing a
      "match" between the clinical VT and the pacemap (28 vs 1). Endocardial activation
      times were not different between both groups (-15 +/- 18 vs -4 +/- 5 ms). In left
      ventricle idiopathic VT, RF ablation was successful in 12 of 13 patients (92%).
      In patients who underwent successful ablation, 1 VT morphology was induced and no
      delta wave-like beginning of the QRS was present; a correlation between clinical
      VT and the pacemap > or = 11 of 12 leads was found and the endocardial activation
      time preceded the QRS (range of -5 to -58 ms [mean -30 +/- 14]). Purkinje
      activity was observed in 5 of 7 patients with an idiopathic VT originating from
      the inferoposterior region but not from the inferoapical region of the left
      ventricle. Four patients (14%) with RV outflow tract idiopathic VT had recurrence
      during a mean follow-up of 2 to 50 months (mean 30 +/- 12). Thus, (1) in RV
      outflow tract idiopathic VT a good pacemap was more important than an early
      endocardial activation time; (2) an optimal pacemap as well as an early
      endocardial activation time were important predictors for successful ablation of
      the left ventricle idiopathic VT; (3) Purkinje activity was recorded in VTs
      arising in the inferoposterior region of the left ventricle; and (4) factors for
      unsuccessful ablation for idiopathic VT were > 1 induced VT morphology, a delta
      wave-like beginning of the QRS, and a VT/pacemap correlation < 11 of 12 leads.
      Idiopathic VT can be successfully ablated with both immediate and long-term
      success.

PMID- 9036751
TI  - Reproducibility of drug efficacy predictions by Holter monitoring in the
      electrophysiologic study versus electrocardiographic monitoring (ESVEM) trial.
      ESVEM Investigators.
AB  - Selection of antiarrhythmic therapy may be based on suppression of spontaneous
      ventricular arrhythmias assessed by Holter monitoring, but the implications of
      discordant Holter results on repeat 24-hour monitoring has not been defined. This
      study examines the frequency and significance of reproducible Holter suppression
      on two 24-hour recordings in the Electrophysiologic Study Versus
      Electrocardiographic Monitoring (ESVEM) trial. Repeat 24-hour Holter monitoring
      was obtained in patients randomized to the Holter monitor limb of the ESVEM
      trial, during the same hospitalization, after a drug efficacy prediction. These
      Holters were not used to define drug efficacy but were subsequently analyzed to
      determine the reproducibility of drug efficacy predictions by Holter monitoring.
      A repeat 24-hour Holter monitor, following the one that predicted drug efficacy,
      was available in 119 patients. Ninety-nine patients (83%) also had suppression
      that met efficacy criteria on the second Holter monitor. There were no
      significant differences in arrhythmia recurrence (p = 0.612) or mortality (p =
      0.638) in patients with concordant Holter results (n = 99; 1-year arrhythmia
      recurrence = 45%; 1-year mortality = 10%) compared with those with discordant
      Holter results (n = 20; 1-year arrhythmia recurrence = 45%; 1-year mortality =
      16%). We conclude that (1) there is discordance between the first effective
      Holter monitor and a repeat Holter monitor in 17% of patients, and (2)
      suppression of ventricular ectopic activity on 2 separate 24-hour Holter monitors
      does not identify a group with a better outcome, nor does failure of suppression
      on the second Holter monitor identify a group with a worse prognosis.

PMID- 9036752
TI  - Right and left ventricular hemodynamic performance during sustained ventricular
      tachycardia.
AB  - Several factors may influence hemodynamic tolerance of a ventricular tachycardia
      (VT) episode but, to date, only VT rate has been used as a major detection
      criterion in selecting implantable cardioverter-defibrillator therapy algorithms.
      We examined hemodynamic changes during VT in humans and a possible correlation
      between left and right ventricular hemodynamic indexes. Right ventricular
      hemodynamic indexes could reflect systemic hemodynamics but previous studies have
      been inconclusive. Patients with coronary artery disease and a history of
      recurrent, sustained VT were studied. Aortic pressure and right and left
      ventricular pressures were simultaneously recorded with 2 dual micromanometer
      tipped high-fidelity pressure catheters during sinus rhythm and during induced
      sustained monomorphic VT. Beat-to-beat analysis was performed using custom-made
      software. Nine patients (7 men, mean age 60 +/- 8 years, mean ejection fraction
      24 +/- 8%) with 11 VT episodes (mean cycle length 283 +/- 48 ms) were studied.
      During VT, left and right ventricular systolic pressures showed a mean decrease
      of 57% and 26%, respectively, with weak correlation (r = 0.67, p = 0.06) between
      both values. There was also an increase in mean left and right ventricular end
      diastolic pressures of 26% and 74%, respectively, and no correlation was seen (r
      = -0.2, p = 0.6). A significant correlation was found between changes in left and
      right ventricular maximal positive dP/dt (55% and 28% decrease, respectively (r =
      0.69, p = 0.03) and between changes in left and right ventricular maximal
      negative dP/dt (64% vs 39% decrease, r = 0.71, p = 0.02). Most ventricular time
      parameters in both ventricles differed significantly during VT compared with
      sinus rhythm; however, only the decrease in right ventricular time to end
      diastolic pressure correlated with the decrease in left ventricular systolic
      pressure, at the 10th VT beat (r = 0.8, p = 0.01). We conclude that left and
      right ventricles are hemodynamically unequally affected during rapid VT. Although
      right ventricular pressures cannot be reliably used to assess changes in the
      hemodynamic status of the left ventricle, additional parameters, such as dP/dt or
      changes in ventricular time intervals, should be further evaluated for inclusion
      in implantable cardioverter-defibrillator algorithms.

PMID- 9036753
TI  - Enalapril reduces QTc dispersion in mild congestive heart failure secondary to
      coronary artery disease.
AB  - This study was designed to investigate the possible mechanisms whereby enalapril
      improves cardiac function and mortality in chronic heart failure. We explored
      potential mechanisms by following 41 patients with early heart failure over the
      course of 1 year. These patients were randomized in a prospective triple-blind
      manner to receive either enalapril or placebo. Over the 1 year, repeated
      measurements were obtained of echocardiographic parameters, glomerular filtration
      rate, renal blood flow, hematocrit, plasma neurohormones, and QTc dispersion.
      Echocardiographic parameters improved with enalapril but deteriorated with
      placebo (cardiac output 4.6 +/- 1.6 to 3.7 +/- 1.5 L/min with placebo, and 4.5 +/
      1.3 to 5.8 +/- 2.0 L/min with enalapril; p <0.01). In contrast, there were no
      significant changes in renal blood flow (518 +/- 185 to 509 +/- 180 ml/min/1.73
      m2 with placebo, and 541 +/- 142 to 504 +/- 162 ml/min/1.73 m2 with enalapril).
      Glomerular filtration rate changed from 79 +/- 20 to 78 +/- 19 ml/min/1.73 m2
      with placebo, and from 85 +/- 21 to 73 +/- 27 ml/min/1.73 m2 with enalapril (p =
      0.051). Enalapril reduced hematocrit (0.414 +/- 0.041 to 0.377 +/- 0.040%)
      significantly more than placebo (0.420 +/- 0.029 to 0.411 +/- 0.023 l/l; p
      <0.01). In addition, enalapril produced a marked reduction in QTc dispersion (93
      +/- 36 to 88 +/- 28 ms with placebo and 93 +/- 35 to 60 +/- 22 ms with enalapril;
      p <0.05). Thus, enalapril significantly reduced hematocrit and reduced QTc
      dispersion in early heart failure. Both of these effects, but especially the
      latter, could be an important mechanism for the reduced mortality seen with
      angiotensin-converting enzyme inhibitors in heart failure. In contrast, renal
      hemodynamics did not parallel either the placebo-induced deterioration in cardiac
      function or the enalapril-induced improvements in cardiac function.

PMID- 9036754
TI  - Prediction of surgical strategy in mitral valve regurgitation based on
      echocardiography. Interuniversity Cardiology Institute of The Netherlands.
AB  - The purpose of this prospective multicenter study of 350 consecutive patients who
      were accepted for mitral valve surgery because of severe regurgitation, was to
      assess the value of preoperative transthoracic and transesophageal
      echocardiography in predicting the surgical strategy in severe mitral
      regurgitation: repair or replacement. The cardiologist predicted the surgical
      strategy on the basis of the echocardiographic examination, according to
      predefined guidelines for repair and replacement. The predicted strategy and
      motivation thereof were compared with the surgical findings and procedure that
      was performed. Agreement on the basis of transthoracic echocardiography was
      reached in 86% of the repair patients and on the basis of transesophageal
      echocardiography in 89%. Agreement on the basis of transthoracic echocardiography
      was reached in 74% of the replacement patients and on the basis of
      transesophageal echocardiography in 75%. This study underlines the potential role
      of echocardiography in predicting the surgical procedure to be applied, provided
      that both surgeon and cardiologist use the same nomenclature and that the
      guidelines for replacement/repair are adhered to. Both transthoracic and
      transesophageal echocardiography appear to be equally accurate in predicting the
      optimal surgical procedure in this respect.

PMID- 9036755
TI  - Effect of warfarin on regional left atrial coagulation activity in mitral
      stenosis.
AB  - Increased regional left atrial (LA) coagulation activity has recently been
      implicated in the pathophysiology of LA thrombus and systemic embolism in mitral
      stenosis (MS). Anticoagulation with warfarin reduces the risk of such
      thromboembolism, but the effect of warfarin on LA coagulation activity is
      unknown. We have addressed this question in MS patients with normal or prolonged
      clotting times. Peripheral venous and LA coagulation activities were measured in
      MS patients on long-term oral anticoagulation, who were predisposed to increased
      LA coagulation activity because of the presence of LA spontaneous echo contrast.
      Patients ceased warfarin 4 days before percutaneous balloon mitral valvuloplasty,
      and had either a normal (n = 15) or prolonged (n = 8) International Normalized
      Ratio (INR) at valvuloplasty. Coagulation activity was assessed during the
      valvuloplasty procedure, but before valve dilation, by measuring levels of
      prothrombin fragment 1 + 2 (F1 + 2), a marker of thrombin generation. The LA F1 +
      2 level exceeded the peripheral venous level in patients with a normal INR (p
      <0.001), but these levels were similar in patients with a prolonged INR (p =
      0.16). Moreover, the LA (p <0.005) and peripheral venous (p <0.03) F1 + 2 levels,
      as well as the LA-peripheral venous F1 + 2 difference (p <0.03) were lower in
      patients with a prolonged INR. These results suggest that anticoagulation with
      warfarin in MS not only reduces systemic coagulation activity but is associated
      with a greater reduction in LA coagulation activity. The latter may contribute to
      the reduced risk of LA thrombus formation that accompanies warfarin therapy in
      MS.

PMID- 9036756
TI  - Natural course of isolated pulmonary valve stenosis in infants and children
      utilizing Doppler echocardiography.
AB  - Most natural history data regarding pulmonary stenosis (PS) were obtained from
      cardiac catheterization studies over 15 to 20 years ago. Selection bias in these
      studies often excluded patients with mild disease and infants. Today, Doppler
      echocardiography allows accurate serial assessments of stenotic lesions in
      patients of all ages. This study evaluates the natural history of PS utilizing
      serial Doppler examinations in the pediatric population. A total of 147 patients
      with PS and serial echocardiographic data were identified. Age at initial
      echocardiogram ranged from 2 days to 15 years, with a mean follow-up of 2.4
      years. Sixteen of 56 patients (29%) initially evaluated within 1 month had a > or
      = 20 mm Hg increase in their peak systolic pressure gradient. Only 7 of 89
      patients (8%) initially evaluated over 1 month had a > or = 20 mm Hg increase.
      Eleven of 40 newborn infants (28%) with mild obstruction had progression to
      moderate or severe PS compared with 10 of 68 patients (15%) initially evaluated
      over 1 month. Moderate PS in the newborn was also more likely to progress
      compared with older children. Of the 16 newborns with > or = 20 mm Hg increases,
      8 developed the increase in < or = 6 months. In contrast, no patient aged >2
      years whose initial gradient was <50 mm Hg developed severe PS. Mild PS may not
      be static, particularly in young infants. Progression in this age group occurs
      more often and more rapidly than in older infants and children.

PMID- 9036757
TI  - Effect of a single high-fat meal on endothelial function in healthy subjects.
AB  - Although there is a well-established relation between serum cholesterol and
      coronary artery disease risk, individual and national variations in this
      association suggest that other factors are involved in atherogenesis. High-fat
      diet associated triglyceride-rich lipoproteins have also been suggested to be
      atherogenic. To assess the direct effect of postprandial triglyceride-rich
      lipoproteins on endothelial function, an early factor in atherogenesis--10
      healthy, normocholesterolemic volunteers--were studied before and for 6 hours
      after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat,
      respectively). Endothelial function, in the form of flow-mediated vasoactivity,
      was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial
      diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum
      lipoproteins and glucose were determined before eating and 2 and 4 hours
      postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially
      to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent
      vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and
      10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05
      compared with low-fat meal data). No changes in lipoproteins or flow-mediated
      vasoactivity were observed after the low-fat meal. Fasting low-density
      lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with
      preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean
      change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated
      with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results
      demonstrate that a single high-fat meal transiently impairs endothelial function.
      These findings identify a potential process by which a high-fat diet may be
      atherogenic independent of induced changes in cholesterol.

PMID- 9036758
TI  - Comparison of left ventricular function using isometric exercise Doppler
      echocardiography in competitive runners and weightlifters versus sedentary
      individuals.
AB  - It is unclear whether cardiovascular responses to heavy isometric exercise are
      changed by intensive training. We evaluated the effects of this type of exercise
      on left ventricular (LV) function in athletes engaged in static and dynamic
      sport, compared with sedentary persons, and looked for peculiarities in static
      athletes' responses that might reflect adaptive mechanisms to their specific
      activity. The study population comprised 45 men (age 24 +/- 5 years): 29 dynamic
      and 16 static athletes (runners and weightlifters, respectively). The control
      group consisted of 20 age and gender-matched healthy sedentary persons. All
      performed 50% of maximal voluntary contraction on a whole-body isometric exercise
      device for 2 minutes. Echocardiographic calculations were determined at rest and
      exercise. Upon exercise, stroke volume, cardiac output, end-diastolic volume, and
      ejection fraction increased significantly in athletes, while end-systolic volume
      and systemic vascular resistance decreased. In sedentary persons, stroke volume
      and resistance remained unchanged, cardiac output and LV volumes increased, and
      ejection fraction decreased from 67 +/- 5% to 60 +/- 5% (p <0.01 compared with
      rest; p <0.0001 compared with athletes). Whereas peak flow velocity decreased
      from 103 +/- 10 to 81 +/- 6 cm/s in sedentary persons, it increased from 112 +/-
      9 to 126 +/- 8 cm/s in the static group and from 120 +/-3 to 126 +/- 9 cm/s in
      the dynamic athletes (p <0.0001 compared with the sedentary group). Mean
      acceleration decreased in the sedentary group, remained unchanged among the
      dynamic athletes, and increased among the static athletes. We conclude that
      cardiovascular responses to heavy isometric exercise are modified by intensive
      training. Athletes, taken as a group, react differently and adapt better than
      sedentary individuals. Moreover, among them, those involved in static sport show
      an improved cardiovascular adaptation to this type of exercise.

PMID- 9036759
TI  - Identification of the anaerobic threshold using double product in patients with
      coronary artery disease.
AB  - This study compared the ventilatory threshold with the double-product break point
      in 104 patients with cardiovascular disease during ramp treadmill testing. The
      high correlation (r = 0.81) between the double-product break point and the
      ventilatory threshold, even in patients taking beta blockers, suggests the former
      method is a viable noninvasive alternative for identifying the anaerobic
      threshold in patients with cardiovascular disease, particularly when expired gas
      analysis is not appropriate or available.

PMID- 9036760
TI  - Frequency of pericardial friction rub ("pericarditis") after direct percutaneous
      transluminal coronary angioplasty in Q-wave acute myocardial infarction.
AB  - The clinical significance of infarct-associated pericarditis was examined in 201
      consecutive patients with acute Q-wave myocardial infarction with successful
      direct percutaneous transluminal angioplasty. A pericardial rub was a reliable
      clinical sign of extensive myocardial damage in patients with direct angioplasty.

PMID- 9036761
TI  - Early chronotropic incompetence predicts the need for atropine during dobutamine
      stress echocardiography.
AB  - Analysis of heart rate responses in 130 patients undergoing dobutamine stress
      echocardiography revealed that heart rate response at 20 microg/kg/min predicted
      the eventual need for atropine in chronotropically incompetent patients.
      Administering atropine at intermediate doses of dobutamine rather than at peak
      stress may reduce test duration and provide a more balanced chronotropic and
      inotropic stress.

PMID- 9036762
TI  - Left atrial function and atrial natriuretic factor/cyclic guanosine monophosphate
      changes in DDD and VVI pacing modes.
AB  - Left atrial systolic function and the plasma of atrial natriuretic factor (ANF)
      and cyclic guanosine monophosphate (cGMP) were investigated as possible markers
      for the development of pacemaker syndrome during VVI pacing. Patients who
      developed pacemaker syndrome during VVI pacing had a significant decrease in left
      atrial emptying fraction and a substantial increase in ANF and cGMP plasma
      levels.

PMID- 9036763
TI  - Utility of patient-activated cardiac event recorders in general clinical
      practice.
AB  - A retrospective study of 729 consecutive patient-activated continuous loop
      recorders shows that these devices provide useful diagnostic information about
      the presence or absence of transient arrhythmias in carefully selected patients
      with certain specific complaints.

PMID- 9036764
TI  - Evolution of left ventricular hypertrophy and function during long-term treatment
      of systemic hypertension with enalapril.
AB  - Continued treatment of hypertensive patients with enalapril reduced left
      ventricular (LV) hypertrophy steadily over a period of 5 years (by which time
      gross structural parameters were normal) and produced no further reduction during
      the following 2 years. Temporary suspension of treatment after 5-year follow-up
      gave rise to an increase in blood pressure, and to deterioration of LV isovolumic
      relaxation time and deceleration of the ventricular filling E wave, both of which
      chiefly reflect the active relaxation of the ventricle.

PMID- 9036765
TI  - Detection of right to left shunts in decompression sickness in divers.
AB  - The diagnostic accuracy of bubble contrast transthoracic and transesophageal
      echocardiography and transcranial Doppler sonography in the detection of patent
      foramen ovale in divers with decompression sickness was assessed. Transcranial
      Doppler has a better positive and negative predictive value than the other
      modalities.

PMID- 9036766
TI  - Prevalence of echocardiographic findings in 554 men and in 1,243 women aged > 60
      years in a long-term health care facility.
AB  - The prevalence of mitral regurgitation, valvular aortic stenosis, aortic
      regurgitation, hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy,
      and of left ventricular hypertrophy was not significantly different in older men
      and women. Older women had a significantly higher prevalence of rheumatic mitral
      stenosis, mitral annular calcium, and left atrial enlargement than older men, and
      older men had a significantly higher prevalence of abnormal left ventricular
      ejection fraction than older women.

PMID- 9036767
TI  - Dobutamine stress echocardiography in the assessment of suspected myocardial
      ischemia in children and young adults.
AB  - In 67 studies in 43 children with suspected coronary artery disease, dobutamine
      stress echocardiography was safe and accurate in diagnosing coronary
      insufficiency. The efficacy and safety of dobutamine echocardiography make it the
      ideal test for diagnosing myocardial ischemia in children.

PMID- 9036768
TI  - Impact of curve distortion errors on intravascular ultrasound measurements and
      three-dimensional reconstructions.
AB  - Intravascular ultrasound distortion errors and longitudinal reconstructions are
      primarily determined by the angle of curvature. The error in commonly encountered
      angles is relatively small.

PMID- 9036770
TI  - Presidential Address of the American Orthopaedic Society for Sports Medicine.

PMID- 9036769
TI  - Deletions in chromosome 22q11 region in cervical aortic arch.
AB  - Two patients with cervical aortic arch are described, both with deletions in
      chromosome 22q11 region, and thymic hypofunction. This suggests that cervical
      aortic arch is part of the spectrum of the CATCH 22 group of defects.

PMID- 9036772
TI  - [Lung transplant in infants: reality or fiction?].

PMID- 9036771
TI  - [Transition between childhood and adulthood in cystic fibrosis].

PMID- 9036773
TI  - [Pediatric donation and transplantation activity in Spain].

PMID- 9036774
TI  - [Evaluation of the tuberculosis infection screening program in pediatric
      population].
AB  - OBJECTIVE: To evaluate a screening program for tuberculosis (TBC) infection in a
      pediatric population in Spain using the tuberculin skin test (TST) and to analyze
      the distribution of the frequencies obtained. DESIGN: The study consists of a
      descriptive analysis carried out on a sample of the pediatric population from
      Mostoles and Alcorcon, two towns belonging to the Community of Madrid with
      192,353 and 141,292 inhabitants, respectively. PATIENTS AND METHODS: A sample of
      2,369 children was analyzed. The TST was performed over a ten-month period by
      trained, voluntary nurses from primary care units. The following variables were
      analyzed: risk factors for TBC infection, BCG vaccination and induration (mm) of
      the TST. In children with positive TST results, a search for infective foci and
      active tuberculosis was performed. RESULTS: The prevalence of TBC infection in
      the infantile population without risk factors was 0.7% (C.I. 95%, 0.4-1). No
      cases were found among children aged 3 months to 2 years. In the sample, 4.2%
      (C.I. 95%, 3.4-5) of the children had one or more risk factors for TBC-infection.
      Among children presenting risk factors for TBC, 5.1% (C.I. 95%, 1.6-11.8) had a
      positive result in the TST. However, 76.2% (C.I. 95%, 52.7-91.8) of children with
      a positive TST, no risk factors could be detected. CONCLUSIONS: Although a
      positive TST was more frequent in children with risk factors, as the majority of
      children in our population lacked risk factors for TBC infection, selective
      screening based on this parameter would not detect most cases of TBC-infection.
      Greater efforts should be made to better identify children with risk factors for
      TBC. According to our results, it is highly advisable to perform the TST once
      during childhood between 10 and 14 years, the period of highest prevalence, for
      both epidemiological and clinical reasons.

PMID- 9036775
TI  - [Language disorders in the light of K-ABC].
AB  - OBJECTIVE: Problems of terminology have hampered the study of dysfunctional
      school age children, and a confusing array of labels has been applied to them.
      This is the case for speech and language disorders. The challenge to the
      pediatrician is to arrive at an integrated diagnosis that will lead to useful
      strategies for intervention. PATIENTS AND METHODS: The K-ABC test, as a new
      instrument in the light of a new conception of intelligence, has been used as a
      tool for assessing language disorders in a sample of 261 preschool children aged
      3 to 6 years. The results were analyzed by the Chi-square test and the stratified
      Chi-square test of Mantel-Haenzel as a discriminator between two variables.
      RESULTS: Bilingualism, father's and mother's educational level and jobs, as
      sociocultural and/or socioeconomic factors, emerged as statistically significant.
      CONCLUSIONS: The main conclusions refer to the ability to discriminate between
      learning and language disabilities and the relationship between language
      disorders and the bilingual condition or sociocultural markers, such as
      profession and academic achievement, of the parents. This article highlights the
      value of pediatrician-psychologist collaborations.

PMID- 9036776
TI  - [The use and attitudes of adolescents toward addictive substances: a prevalence
      study].
AB  - OBJECTIVE: The purpose of this study was to know the use of addictive substances
      by adolescents of the city of Barcelona (Catalonia, Spain). PATIENTS AND METHODS:
      Data were obtained from an anonymous and self-administered questionnaire about
      tobacco use, alcohol use and non-institutionalized drug abuse. participants were
      students in 3 degrees BUP (16-17 years old) of twelve institutes that are
      representative of the different districts of the city. The survey was made during
      the 1991-1992 school year. RESULTS: Among the 426 individuals included, 32.2%
      reported use of tobacco, 59.2% alcohol, and 16.4% marijuana. Tobacco use was
      higher among females (p = 0.05), and that of alcohol (p < 0.0001) and other drugs
      (p = 0.02) higher among males. The parents' smoking behavior was significantly
      associated with the use of non-institutionalized drugs (p = 0.01). There was a
      positive and significant association among the use of all three kinds of
      addictive substances (p < 0.0001). CONCLUSIONS: The prevalence of tobacco,
      alcohol and non-institutionalized drug use by students in this age range is high.
      Compared with previous studies in this population we can appreciate a decreasing
      trend of use.

PMID- 9036777
TI  - [Eosinophil cationic protein in the asthmatic infant: correlation with the clinic
      and pulmonary function].
AB  - PATIENTS AND METHODS: Serum eosinophil cationic protein (ECP) was measured in 99
      chronic asthmatic patients (51 males and 48 females) with a mean age of 10.59
      years and correlated with the number of eosinophils, lung function, symptoms in
      the last 6 months and clinical scoring (that reflecting the clinical situation
      during the last 15 days). RESULTS: Serum ECP showed a significant correlation
      with the total number of eosinophils (p < 0.001, R = 0.44), clinical scoring (p <
      0.05, R = 0.26), number of inhaled beta 2-agonist doses needed in the last 15
      days (p < 0.05, R = 0.26), forced expiratory volume during 1 second (FEV1; p <
      0.01, R = -0.27), forced vital capacity (FVC; p < 0.05, R = -0.23), maximal mid
      expiratory flow (FEF25-27; p < 0.001, R = -0.37). However, there was no
      significant correlation between the total number of eosinophils and the clinical
      situation of the children or the FEV1, but we found a significant correlation
      with the FEF25-27. Patients with ECP < 20 had better results on lung function
      tests than patients with ECP > 20 (FEV1: 108.89 +/- 17.7 vs 100.5 +/- 22 (p <
      0.05), FEF25-27: 93.81 +/- 24.4 vs 75.21 +/- 24.5 (p < 0.001). CONCLUSIONS: The
      findings of this study suggest that the ECP level is a good marker of the
      situation of asthma in childhood. The levels of ECP will probably be able to help
      us to evaluate the degree of bronchial inflammation that neither the clinical
      state nor the lung function define completely.

PMID- 9036778
TI  - [Diagnosis of otitis media with effusion by acoustic reflectometry].
AB  - OBJECTIVE: Acoustic reflectometry is a new technique based on a sonar that
      enables the diagnosis of middle ear effusion. Our objective was to assess its
      value and to know the cut-off figure for pathology. PATIENTS AND METHODS: In 586
      children, from 1 month to 14 years of age, we performed bilateral otoscopy
      looking for signs of middle ear effusion. Afterwards, 3 measurements with the
      acoustic otoscope (ENT, Inc.) were taken and the results between the two methods
      compared. RESULTS: There was a significant association (p < 0.0001, Chi-squared)
      between results > 4 and middle ear effusion with a sensitivity of 84.2% and a
      specificity of 98.9%. CONCLUSIONS: Acoustic reflectometry has shown to be a very
      quick (< 10 seconds/ear), accurate and objective technique. It is painless and
      easy. It can be made in any child, without collaboration (crying or moving) and
      at any age.

PMID- 9036779
TI  - [Serum antibodies against Haemophilus influenzae in children from the province of
      Valladolid (Spain)].
AB  - OBJECTIVE: Invasive infections by Haemophilus influenzae type b (Hib) in children
      are increasing in Spain. Moreover, they are becoming more resistant to
      antibiotics. Currently, effective vaccines against Hib are available and their
      inclusion in the routine schedule of immunizations is discussed. Knowledge of the
      childhood serology appears to be useful in decision making. PATIENTS AND METHODS:
      Two hundred and thirty-five normal children, between 1 month and 15 years of age,
      were studied. Thirty-six adults sera were also included as controls.
      Polysaccharide of Hib was conjugated with tyramine and used to coat polystyrene
      microtitration plates. The determination of antibodies was performed by ELISA and
      the results are expressed in optical density units. The mean level of antibodies
      present in 6 sera from a patient with Bruton syndrome (17 uu), just before
      degammaglobulinotherapy, was considered as the limit of protection. RESULTS: The
      antibody titer correlated with age (p < 0.001). The levels in children younger
      than 3 years (25.7 +/- 32.5) were lower than in older children (p < 0.001). Of
      the children younger than 3 years of age, 53% did not reach the protective level
      of antibodies, compared to 15.2% of those between 3-6 years and 22.7% of children
      between 6 and 14 years. Whereas the mean antibody level increased with age in
      positive sera, the percentage of seropositive children decreased after 3 years of
      age. CONCLUSIONS: The number of children spontaneously protected against Hib is
      low (47%) until 3 years of age. Nevertheless, this number increases rapidly after
      this age. Immunization must be restricted to this age group.

PMID- 9036780
TI  - [Feeding habits of a sample of children under 20 months of age in Madrid].
AB  - OBJECTIVE: To know the feeding habits of children of different socioeconomic
      groups during the first year and a half of life in Madrid. PATIENTS AND METHODS:
      The mothers of 344 children between 3 and 19 months who attended two vaccination
      centers of the Regional Health Authorities of Madrid were interviewed in detail
      using the dietary history method supplemented with questions on milk feeding and
      weaning. The sample was stratified into three socioeconomic groups, low middle
      and high, each group comprising about a third of the sample. RESULTS: In general,
      children were fed according to actual pediatric recommendations. Deviations were
      that breast-feeding was stopped too early, complementary feeding was introduced
      somewhat early and mothers were often found not to understand gluten nor did they
      know which products contain it. The children in this study were remarkably
      similarly fed regardless of socioeconomic group. CONCLUSIONS: The pediatrician
      should know where mothers may deviate from the recommendations to prevent feeding
      errors because o misunderstanding or ignorance.

PMID- 9036781
TI  - [Rotavirus: clinical and epidemiological study in hospitalized children under two
      years of age].
AB  - OBJECTIVE: Rotavirus (RV) remains as the leading cause of acute diarrheal disease
      in early infancy; nevertheless, there are few epidemiological studies in our
      geographical area. In order to better understand the clinical epidemiology of RV,
      we have carried out a revision of acute diarrheal illnesses in the area of
      Santiago de Compostela (Spain) in children younger than 2 years of age who needed
      hospitalization during a 12 month period. PATIENTS AND METHODS: In 155 children
      with suspected gastroenteritis, 339 stool samples were collected and separated
      into two groups depending upon the presence or not of RV antigen. RESULTS: In the
      group of RV-positive stool patients, the occurrence of vomiting, fever, need of
      intravenous fluid rehydration (p = 0.01), respiratory symptoms (p < 0.01), the
      incidence during winter, as well as the development of disaccharidase depression
      (p < 0.001), were more frequent as compared with the group of children of similar
      age who did not present RV in faeces. There was no difference between the two
      groups regarding the presence of other potential enteropathogen agents (p >
      0.05). The incidence of RV-positive faeces per 100 hospitalized infants/year was
      10.5 and that of infants with RV diarrhea who needed hospitalization was 5.5%/
      year. CONCLUSIONS: There was no mortality related with gastroenteritis, but RV
      infection remains an important cause of morbidity and socioeconomic burden.
      Nosocomially acquired hospital infections add to morbidity and the cost of
      hospitalization.

PMID- 9036782
TI  - [Lung transplantation in cystic fibrosis].
AB  - OBJECTIVE: Since 1990 we have performed 40 lung transplants in the Hospital "La
      Fe" in Valencia. Nine of them have been performed in cystic fibrosis patients,
      which is the subject of this paper. PATIENTS AND METHODS: The mean age of the
      patients was 19.8 years, with the youngest patient being 14 years of age. In
      regards to patient selection, it is important to mention that one had a previous
      lobectomy, another one a thoracic deformity due to long term atelectasis and one
      needed intubation for hemoptysis within the 7 days before the lung transplant.
      Prophylaxis with imipenem and cyprofloxicin, aerosolized colistin and
      amphotericin B, prompt weaning and intensive respiratory physiotherapy were
      important for controlling postoperative infection. RESULTS: With 15.3 months as
      the mean follow-up (range 36-3), 3 year survival was 87.5%. Pulmonary infection,
      which was the most frequent complication, had a good response to adequate
      antibiotic treatment. The main postoperative problem pertained to the bronchial
      suture with 2 partial dehiscences, 2 stenoses and one bronchopleural fistula by
      Aspergillus, all of which were resolved with conservative procedures without
      surgery. CONCLUSIONS: Middle and long term evolution in these patients shows an
      excellent quality of life with spirometric and ergometric tests within the normal
      range.

PMID- 9036783
TI  - [Encephalitis due to measles].
AB  - OBJECTIVE: We present seven cases of acute encephalitis following measles, which
      were diagnosed during the epidemic that occurred in Spain in 1986. PATIENTS AND
      METHODS: We studied seven patients diagnosed of encephalitis due to measles. The
      diagnosis of measles was a made by the presence of a characteristic morbiliform
      rash and the detection of specific IgM antibodies. The diagnosis of encephalitis
      was based on the symptoms and the routine examinations of blood, CSF, EEG, CT,
      ophthalmic exploration and the study of the audiovisual evoked potentials.
      RESULTS: The patients were between 5 and 9 years of age. None of them had been
      previously vaccinated for measles. The symptoms of encephalitis occurred 1 to 12
      days after the appearance of the rash and the most frequent symptoms were
      drowsiness and vomiting. All of the patients had EEG abnormalities that returned
      to normal 1 to 18 months after the diagnosis. One patient presented CT
      abnormalities. CSF examination revealed an increase of the cell count in one
      case. The ophthalmic exploration was normal except in one of the patients which
      had optic neuritis. There were no abnormalities in the audiovisual evoked
      potentials. All of the cases showed good evolution. Five years later, all of the
      patients have had a normal development. CONCLUSIONS: The correct vaccination of
      measles can eradicate this disease.

PMID- 9036784
TI  - [Continuous hemofiltration. Development of an experimental model].
AB  - OBJECTIVE: Continuous hemofiltration is an extracorporeal technique used to
      eliminate water and solutes by convective transport through a hemofilter. The aim
      of this study was to develop an experimental model of arterio-venous and veno
      venous continuous hemofiltration in order to gain experience before its clinical
      application in human neonates. MATERIALS AND METHODS: Twelve white New Zealand
      adult rabbits were anesthetized, tracheotomized and connected to a continuous
      flow neonatal ventilator. Continuous arterio-venous hemofiltration (n = 6) was
      performed via catheters placed in the carotid artery and jugular vein and veno
      venous hemofiltration (n = 6) by a double-lumen catheter located in the inferior
      vena cava. Heart rate, arterial pressure, pH and blood gases, and the volume of
      ultra-filtrate were monitored and recorded for a three hour period. RESULTS: In
      both groups a high rate of ultrafiltration was achieved. The volume of
      ultrafiltration decreased somewhat during the second hour and remained stable
      thereafter. No hemodynamic changes were detected. CONCLUSIONS: The development of
      an experimental model for continuous arterio-venous and veno-venous
      hemofiltration in rabbits, facilitated the implantation of these techniques in
      human neonates. The model may be used to train the staff of the Neonatal
      Intensive Care Unit and to eliminate difficulties with vascular access and the
      care of extracorporeal lines.

PMID- 9036785
TI  - [Benign gingival granular cell tumor in the newborn: congenital epulis].
AB  - Gingival granular cell tumor, or congenital epulis, was first described by
      Neumman in 1871 and subsequently 201 cases have been published in 173 patients.
      It is an uncommon benign tumor that is present like a pedunculated, smooth
      surfaced, isolated lesion on the alveolar mucosa of the maxillar of the newborn
      child. Its firm consistency and variable size can occasionally cause problems in
      the child's breathing or feeding. This tumor is easily diagnosed clinically and,
      although spontaneous regression of the tumor mass has occasionally been reported,
      the current treatment is surgical removal. Two new cases of congenital epulis are
      reported and a literature review is included.

PMID- 9036786
TI  - [Clinical diagnosis of Down's syndrome based on 11 signs. Epidemiological
      analysis of the specificity of the studied signs].
AB  - OBJECTIVE: Down's syndrome (trisomy 21) is the most frequent viable chromosomal
      abnormality, as well as the only one that can be postnatally diagnosed on the
      basis of a series of clinical signs. However, none is specific by itself. It is
      generally accepted that the diagnosis can be made on the basis of the concurrence
      of a large number of signs. Nevertheless, since most of the clinical signs can be
      observed in the general population, each one of them has a different level of
      specificity for the diagnosis of Down's syndrome, depending on its frequency in
      every population. PATIENTS AND METHODS: We have studied in our population the
      frequency and specificity of 11 signs for the diagnosis of Down's syndrome by
      using data from the Spanish Collaborative Study of Congenital Malformations
      (ECEMC). RESULTS: The analysis of the 11 signs shows great specificity for some
      of them and for the concurrence of four or more. CONCLUSIONS: We consider that
      although the final diagnosis will come from chromosomal analysis, it can be very
      useful to have indicators available for the clinical diagnosis at birth. This is
      extremely important so that the corresponding chromosomal analysis is immediately
      performed, which will result in early and correct information to the parents.

PMID- 9036787
TI  - [Inadequate breast feeding position syndrome].

PMID- 9036788
TI  - [Cranial fasciitis in childhood: a case report and literature review].

PMID- 9036789
TI  - [Nasal dermoid sinus. Case presentation].

PMID- 9036790
TI  - [Alloimmune neonatal neutropenia. Treatment with granulocyte colony- stimulating
      factor].

PMID- 9036791
TI  - [Patient with congenital lumbosacral hypertrichosis].

PMID- 9036792
TI  - [Introduction to molecular biology and its application to pediatrics (2):
      purification of nucleic acids].

PMID- 9036793
TI  - [Immunoglobulins and corticoids in Guillain-Barre syndrome: a report of a new
      case. Letter].

PMID- 9036794
TI  - [Eradication treatment of Helicobacter pylori in children with triple therapy:
      can we do it in two weeks? Letter].

PMID- 9036795
TI  - [The treatment of children with Helicobarter pylory by triple therapy can be
      shortened without the risk of losing it eradicating efficacy. Letter].

PMID- 9036796
TI  - [Comments on a clinical case].

PMID- 9036797
TI  - Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with
      AIDS. A randomized, controlled trial.
AB  - BACKGROUND: Cytomegalovirus (CMV) retinitis is the most common intraocular
      infection in patients with the acquired immunodeficiency syndrome (AIDS). If left
      untreated, it may lead to progressive destruction of retinal tissue and
      blindness. Cidofovir is a nucleotide analogue of cytosine that has potent,
      prolonged in vitro and in vivo activity against herpesviruses, including many CMV
      isolates that are resistant to ganciclovir and foscarnet. OBJECTIVE: To determine
      whether intravenous cidofovir delays progression of previously untreated CMV
      retinitis. DESIGN: Randomized, controlled trial comparing immediate with deferred
      cidofovir treatment. Patients in the deferred treatment group were eligible to
      receive cidofovir after progression of CMV retinitis was documented by retinal
      photography. SETTING: Eight academic medical centers and an independent center
      that read retinal photographs. PATIENTS: 48 patients with AIDS and previously
      untreated peripheral CMV retinitis who were randomly assigned to immediate (n =
      25) or deferred treatment (n = 23). INTERVENTION: Intravenous cidofovir, 5 mg/kg
      of body weight, once weekly for 2 weeks and then once every other week. To
      minimize nephrotoxicity, oral probenecid and intravenous hydration with normal
      saline were administered with each cidofovir infusion. MEASUREMENTS: Progression
      of CMV retinitis was assessed by bilateral, full-field retinal photographs that
      were read by an ophthalmologist who was masked to treatment assignment. Incidence
      of side effects, changes in visual acuity, effect on CMV shedding in urine and
      blood, and mortality were also assessed. RESULTS: The median time to progression
      of CMV retinitis was 22 days (95% CI, 10 to 27 days) in the deferred treatment
      group and 120 days (CI, 40 to 134 days) in the immediate treatment group (P <
      0.001). Neutropenia (15%) and proteinuria (12%), both asymptomatic, were the most
      common serious adverse events considered to be possibly related to cidofovir.
      Cidofovir treatment was discontinued in 10 of 41 patients (24%) because of
      protocol-defined treatment-limiting nephrotoxicity. Transient reactions to
      probenecid, including mild to moderate constitutional symptoms or nausea,
      occurred in 23 of 41 patients (56%) and were dose limiting in 3 (7%).
      CONCLUSIONS: Cidofovir was efficacious in delaying progression of previously
      untreated CMV retinitis. Treatment was associated with manageable side effects;
      strict adherence to monitoring of renal function before cidofovir was
      administered and concomitant administration of probenecid and saline hydration
      appeared to minimize drug-related nephrotoxicity.

PMID- 9036798
TI  - Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the
      HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial.
      Studies of Ocular complications of AIDS Research Group in Collaboration with the
      AIDS Clinical Trials Group.
AB  - BACKGROUND: Cytomegalovirus (CMV) retinitis is a common infection and a major
      cause of visual loss in patients with the acquired immunodeficiency syndrome
      (AIDS). OBJECTIVE: To evaluate intravenous cidofovir as a treatment for CMV
      retinitis. DESIGN: Two-stage, multicenter, phase II/III, randomized, controlled
      clinical trial. SETTING: Ophthalmology and AIDS services at tertiary care medical
      centers. PATIENTS: 64 patients with AIDS and previously untreated, small,
      peripheral CMV retinitis lesions (that is, patients at low risk for loss of
      visual acuity). INTERVENTION: Patients were randomly assigned to one of three
      groups: the deferral group, in which treatment was deferred until retinitis
      progressed; the low-dose cidofovir group, which received cidofovir, 5 mg/kg of
      body weight once weekly for 2 weeks, then maintenance therapy with cidofovir, 3
      mg/kg once every 2 weeks; or the high-dose cidofovir group, which received
      cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with
      cidofovir, 5 mg/kg once every 2 weeks. To minimize nephrotoxicity, cidofovir was
      administered with hydration and probenecid. MEASUREMENTS: Progression of
      retinitis, evaluated in a masked manner by a fundus photograph reading center;
      the amount of retinal area involved by CMV; the loss of visual acuity; and
      morbidity. RESULTS: Median time to progression was 64 days in the low-dose
      cidofovir group and 21 days in the deferral group (P = 0.052, log-rank test). The
      median time to progression was not reached in the high-dose cidofovir group but
      was 20 days in the deferral group (P = 0.009, log-rank test). Analysis of the
      rates of increase in the retinal area affected by CMV confirmed the data on time
      to progression. The three groups had similar rates of visual loss. Proteinuria of
      2+ or more occurred at rates of 2.6 per person-year in the deferral group, 2.8
      per person-year in the low-dose cidofovir group (P > 0.02), and 6.8 per person
      year in the high-dose cidofovir group (P = 0.135). No patient developed 4+
      proteinuria, but two cidofovir recipients developed persistent elevations of
      serum creatinine levels at more than 177 mumol/L (2.0 mg/dL). Reactions to
      probenecid occurred at a rate of 0.70 per person-year. CONCLUSIONS: Intravenous
      cidofovir, high- or low-dose, effectively slowed the progression of CMV
      retinitis. Concomitant probenecid and hydration therapy, intermittent dosing, and
      monitoring for proteinuria seemed to minimize but not eliminate the risk for
      nephrotoxicity.

PMID- 9036799
TI  - Effect of cytomegalovirus infection status on first-year mortality rates among
      orthotopic liver transplant recipients. The Boston Center for Liver
      Transplantation CMVIG Study Group.
AB  - BACKGROUND: To reduce the mortality rate associated with liver transplantation,
      it is important to identify the risk factors for increased mortality among liver
      transplant recipients. It has been suggested that cytomegalovirus (CMV) infection
      is one such risk factor, but no studies have examined mortality rates associated
      with the CMV serologic status of the donor and recipient by using multivariate
      techniques. OBJECTIVE: To study the effect of CMV on 1-year mortality rates in
      orthotopic liver transplant recipients. DESIGN: Intention-to-treat analysis of a
      cohort. PATIENTS: 146 liver transplant recipients who were enrolled in a
      multicenter, randomized, placebo-controlled intervention trial. SETTING: Four
      university-affiliated transplantation centers. RESULTS: 1-year mortality rates
      for the four strata of donor and recipient CMV serologic status before
      transplantation were as follows: seronegative donor and recipient, 11%;
      seronegative donor and seropositive recipient, 22%; seropositive donor and
      recipient, 30%; and seropositive donor and seronegative recipient, 44% (P =
      0.0091). Multivariate analysis using a time-dependent Cox proportional hazards
      model showed that retransplantation (relative risk, 4.6 [95% CI, 1.9 to 10.7]; P
      < 0.001); total number of units of blood products administered during
      transplantation (relative risk, 1.006 per unit [CI, 1.003 to 1.010]; P < 0.001);
      and presence of CMV disease (relative risk, 3.9 [CI, 1.8 to 8.5]; P < 0.001),
      invasive fungal disease (relative risk, 3.3 [CI, 1.5 to 7.1]; P = 0.0020), and
      bacteremia (relative risk, 2.5 [CI, 1.2 to 5.2]; P = 0.0136) were independently
      associated with higher mortality rates. If post-transplantation variables that
      were highly correlated with donor and recipient CMV serologic status were
      restricted from the model, donor and recipient CMV serologic status was the only
      pretransplantation variable independently associated with higher mortality rates
      (P = 0.002). CONCLUSION: Donor and recipient CMV serologic status is a
      significant pretransplantation determinant for death in liver transplant
      recipients.

PMID- 9036800
TI  - Management strategies for Helicobacter pylori-seropositive patients with
      dyspepsia: clinical and economic consequences.
AB  - BACKGROUND: Noninvasive testing for Helicobacter pylori is widely available and
      has been considered as an initial management strategy for uninvestigated
      dyspepsia. However, data to guide clinicians in the management of patients with
      dyspepsia who are seropositive for H. pylori are lacking. OBJECTIVE: To examine
      the economic, clinical, and policy implications of alternative initial management
      strategies for patients with uninvestigated dyspepsia who are seropositive for H.
      pylori. DESIGN: Decision analysis comparing the costs and outcomes of initial
      anti-H. pylori therapy and initial endoscopy. PATIENTS: Helicobacter pylori
      seropositive patients with dyspepsia. MEASUREMENTS: Cost estimates were obtained
      from the Medicare reimbursement schedule and a health maintenance organization
      pharmacy. Probability estimates were derived from the medical literature.
      RESULTS: Initial endoscopy costs an average of $1276 per patient, whereas initial
      anti-H, pylori therapy costs $820 per patient; the average saving is $456 per
      patient treated. The financial effect of a 252% increase in the use of
      antibiotics for initial H. pylori therapy is more than offset by reducing the
      endoscopy workload by 53%. Endoscopy-related costs must be reduced by 96% before
      the two strategies become equally cost-effective. In patients with nonulcer
      dyspepsia, the financial benefits of initial anti-H. pylori therapy are not
      substantially affected by varying the rates of H. pylori eradication, the
      complications of antibiotics, or the response of symptoms to cure of H. pylori
      infection. CONCLUSIONS: In H. pylori-seropositive patients with dyspepsia,
      initial anti-H. pylori therapy is the most cost, effective management strategy.
      Randomized studies of these strategies that evaluate outcomes and patient
      preferences are needed to optimize management decisions. In the meantime, unless
      physicians are concerned about resistance to antimicrobial agents or the lack of
      proven benefit of anti-H. pylori therapy in nonucler dyspepsia, the strategy
      outlined in this analysis can be used as a basis for management and policy
      decisions about H. pylori-seropositive patients with dyspepsia.

PMID- 9036801
TI  - Use of testosterone to prevent cyclophosphamide-induced azoospermia.
AB  - BACKGROUND: Prepubertal patients receiving chemotherapy are relatively resistant
      to cyclophosphamide-induced germinal cell alterations. OBJECTIVE: To study the
      possible protective effect of testosterone used to inhibit germinal cell activity
      in men who are receiving cyclophosphamide. DESIGN: Randomized, clinical trial.
      SETTING: University medical center. PATIENTS: 15 patients with the nephrotic
      syndrome who were treated with cyclophosphamide for 6 to 8 months. INTERVENTION:
      Five patients received daily oral cyclophosphamide, five received
      cyclophosphamide in monthly bolus injections, and five received monthly
      intravenous boluses of cyclophosphamide plus testosterone (100 mg intramuscularly
      every 15 days). MEASUREMENTS: Sperm counts, serum follicle-stimulating hormone
      levels, and serum luteinizing hormone levels were measured before, during, and
      after treatment with cyclophosphamide alone or cyclophosphamide plus
      testosterone. RESULTS: The 10 patients who did not receive testosterone became
      azoospermic during cyclophosphamide therapy. In only 1 of the 10 patients did the
      sperm count return to normal 6 months after discontinuation of therapy. Follicle
      stimulating hormone levels were elevated in these patients (mean +/- SE, 19.20 +/
      1.28 IU/L in patients receiving oral cyclophosphamide and 16.04 +/- 2.22 IU/L in
      patients receiving intravenous cyclophosphamide alone). All 5 patients who
      received testosterone became azoospermic or severely oligospermic during
      treatment but had a normal sperm count 6 months after the discontinuation of
      therapy. In these patients, the mean sperm count was 45.78 +/- 3.89 x 10(6)/mL
      and follicle-stimulating hormone levels were normal (5.08 +/- 0.56 IU/L).
      CONCLUSION: Testosterone given to men before and during an 8-month cycle of
      cyclophosphamide therapy for the nephrotic syndrome may preserve fertility.

PMID- 9036802
TI  - Mechanisms determining course and outcome of diabetic patients who have had acute
      myocardial infarction.
AB  - PURPOSE: To review the pathogenic mechanism that lead to the poor prognosis of
      diabetic patients after myocardial infarction and to determine the efficacy of
      current interventions for myocardial infarction in these patients. DATA SOURCES:
      Search of the MEDLINE database from 1985 to 1995, using the keywords diabetes,
      myocardial infarction, and cardiomyopathy, and a search of the reference
      citations of relevant articles. STUDY SELECTION: Experimental and clinical
      studies on myocardial infarction in diabetic patients and basic research studies
      relevant to this topic. DATA SYNTHESIS: The excess in-hospital mortality of
      diabetic patients results primarily from an increased incidence of congestive
      heart failure. Several combined mechanisms reduce the compensatory ability of the
      noninfarcted myocardium; such mechanisms include preexisting congestive heart
      failure caused by diabetic cardiomyopathy, severe coronary artery disease,
      decreased vasodilatory reserve of epicardial and resistance arteries, and
      possibly abnormal metabolism of myocardial substrate. Late mortality results from
      increased reinfarction rates caused by the diffuse nature of the atherosclerotic
      disease and hypercoagulable state. Platelet hyperactivity, reduced fibrinolytic
      capacity, increased concentrations of hemostatic proteins, and endothelial
      dysfunction promote thrombosis at the site of plaque rupture. Autonomic
      neuropathy predisposes patients to ventricular arrhythmias. Thrombolytic agents,
      aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors are
      effective in patients with diabetes. CONCLUSIONS: In the thrombolytic era,
      mortality rates of diabetic patients who have had acute myocardial infarction
      remain 1.5 to 2 times higher than those in nondiabetic patients. This increased
      mortality rate is caused by diverse mechanisms that affect myocardial function
      and blood supply and by the tendency toward thrombosis in diabetic patients.
      Current therapies for myocardial infarction are effective in these patients.
      Improved metabolic control may also decrease mortality rates.

PMID- 9036803
TI  - Therapy for adults with refractory chronic immune thrombocytopenic purpura.
AB  - Adult chronic immune thrombocytopenic purpura (ITP) is a common hematologic
      disorder; about 14,000 to 16,000 new cases occur each year in the United States.
      Initial treatment with corticosteroids and splenectomy results in normal or
      "safe" platelet counts in more than 70% of patients. Treatment of patients
      refractory to these two treatments is difficult. This paper describes a
      structured approach to therapy that is based on a literature review and personal
      experience, including experience with treatment of chronic ITP in special
      situations (such as emergent bleeding, pregnancy, and central nervous system
      bleeding). Treatment of most patients with chronic ITP is fairly straightforward,
      but management of patients refractory to corticosteroids and splenectomy can be
      difficult. Large, randomized studies are clearly needed to better evaluate the
      many types of treatment that are recommended for refractory patients.

PMID- 9036804
TI  - Helicobacter pylori: when to test, when to treat.

PMID- 9036805
TI  - Idiopathic thrombocytopenic purpura: lessons from a guideline.

PMID- 9036806
TI  - Diagnosis and treatment of idiopathic thrombocytopenic purpura: recommendations
      of the American Society of Hematology. The American Society of Hematology ITP
      Practice Guideline Panel.
AB  - To develop guidelines for the diagnosis and management of idiopathic
      thrombocytopenic purpura (ITP) and to document the extent to which those
      guidelines are based on either scientific evidence or opinion, the AMerican
      Society of Hematology established a panel composed of 13 hematologists with
      expertise in ITP, a clinical epidemiologist, and a practice guidelines
      methodologist. A comprehensive review was done of all published English-language
      studies that met explicit inclusion criteria and that evaluated the natural
      history of ITP or the effectiveness of testing and treatment options for ITP. The
      quality of each study was graded by two reviewers using formal methodologic
      rules. In subject areas for which data was inadequate, recommendations were based
      on opinion and were derived by using a formal screening procedure. Confidential
      questionnaires were used to survey the hematologists on the panel about the
      appropriateness of testing and treatment options in hundreds of clinical
      scenarios. Practice recommendations were derived from the mean appropriateness
      scores for each indication. Voting was kept confidential to give each panel
      member an equal voice and to limit biases introduced by group dynamics. The
      recommendations were peer reviewed by eight outside experts. This report focuses
      on data and on recommendations for adults with ITP. Little high-quality
      scientific evidence with which to assess the efficacy of diagnostic tests and
      treatments for ITP is available. The opinion of the panel was that most
      diagnostic tests are unnecessary in the routine work-ups of patients suspected of
      having ITP and that ITP accompanied by severe bleeding requires treatment with
      glucocorticoids, intravenous immunoglobin, and other measures. However, treatment
      and hospitalization is often unnecessary when patients have only mild or moderate
      thrombocytopenia or minimal bleeding. Special therapeutic measures are sometimes
      indicated in pregnant women with ITP.

PMID- 9036807
TI  - First love.

PMID- 9036808
TI  - Once-daily aminoglycoside dosing.

PMID- 9036809
TI  - Effects of dietary protein on renal disease.

PMID- 9036810
TI  - Effects of dietary protein on renal disease.

PMID- 9036811
TI  - Visceral leishmaniasis in southern Sudan.

PMID- 9036812
TI  - Fluconazole suspension for oropharyngeal candidiasis unresponsive to tablets.

PMID- 9036813
TI  - Serotonin reuptake inhibitor unmasks a pheochromocytoma.

PMID- 9036815
TI  - A further fond farewell to shy and drager.

PMID- 9036814
TI  - Mammography use in black women.

PMID- 9036816
TI  - Midline catheters: the final chapter.

PMID- 9036817
TI  - [Lymphadenectomy and nerve sparing technique in radical surgery of rectal
      cancer].
AB  - The extension that should be given to lateral lymphadenectomy in the surgical
      treatment of extraperitoneal rectal cancer has not yet been assessed because of
      the difficulty of realizing randomized prospective clinical trials. The
      theoretical advantage of an extended lateral lymphadenectomy is represented by an
      accurate staging of the tumour in patients undergoing surgery for possible
      curative resection; even if the high percentage (20 per cent) of pelvic node
      metastasis was already demonstrated, the prognostic impact of lateral
      lymphadenectomy was not proven until now. The results of the Literature
      demonstrated that an advanced rectal cancer can not be treated only by
      conventional surgery: radical surgery (with total mesorectal excision and pelvic
      lymphadenectomy) or, in alternative, a combined approach-chemo
      radiotherapy+surgery-should-be applied in order to improve the 5-year survival
      and to reduce the percentage of local recurrence. With regard to surgery the main
      disadvantage for an extended lateral dissection is represented by the high
      incidence of urinary and sexual dysfunctions. The nerve-sparing technique, when
      combined to pelvic lymphadenectomy, allows preservation of autonomic innervation
      to the pelvis. The results of our experience demonstrated that nerve-sparing
      technique is an effective procedure that reduces the incidence of urinary and
      sexual dysfunctions when accurately performed.

PMID- 9036818
TI  - [Prognostic risk factors in patients operated on for perforated peptic ulcer. A
      retrospective analysis of critical factors of mortality and morbidity in a series
      of 40 patients who underwent simple closure surgery].
AB  - STUDY OBJECTIVE: To identify factors affecting mortality and morbidity in
      patients operated on for perforated peptic ulcer. DESIGN: Retrospective analysis.
      SETTING: University Hospital, Italy. PATIENTS: Forty patients consecutively
      operated on for perforated peptic ulcer by simple suture procedure performed
      either by laparotomy (n = 26) or laparoscopic (n = 14) approach. MEASUREMENTS AND
      MAIN RESULTS: Mortality was 20% (n = 8) and morbidity in survivors was 25% (n =
      8). Compared to survivors, non-survivors were older (mean age 79.3 yrs. vs 60.0
      yrs., p < 0.01), had worse APACHE II and SAPS scores (mean 20.1 vs 8.5, p <
      0.001; and 13.1 vs. 5.5, p < 0.0001 respectively), were treated later (mean
      interval from outbreak of symptoms to surgery 30.8 hrs. vs. 11.1 hrs., p < 0.01),
      and the size of their perforation was larger (mean 15.1 mm. vs. 8.6 mm, p <
      0.05). The laparoscopic approach was the only factor that significantly was
      associated with morbidity in survivors (p < 0.01). The presence of at least two
      risk factors, enhanced the probability of death. CONCLUSION: Old age, great
      APACHE II and SAPS scores, delay in treatment and large size of the perforation
      were associated significantly to mortality in perforated peptic ulcer patients.
      Efforts should be made perioperatively for patients having these risk factors.

PMID- 9036819
TI  - [Evaluation of costs in surgery of inguinal hernia. Day surgery and one day
      surgery versus ordinary admission].
AB  - The authors have completed an analytic research about costs of hospitalization
      and treatment for inguinal hernioplasty and costs of anesthesiologic and surgical
      techniques and hospitalization regimen. The authors consider possible in about
      50% of cases the tension-free hernioplasty carried out with local anesthesia and
      day or one day surgery regimen and they have estimated that it is very less
      costly then traditional herniorraphy carried out with general anesthesia and
      hospitalization: L. 1.056.075 versus L. 2.252.650. In Emilia-Romagna we could
      have a considerable cost-saving, even if only the 50% of patients treated for
      uncomplicated inguinal hernia every year (7.133 patients with mean hospital stay
      = 5,8 days and total hospitalization = 41.731 days during 1993) could benefit by
      treatment in one day surgery regimen. In fact, leaving out of account the
      advantage of the rapid return the patient to work, the costs of hospital stay,
      esteemed in L. 25.038.600.000, would be L. 8.558.700.000. A considerable increase
      of one day surgery hernioplasties should be expected by the hospital
      administration in budget planning.

PMID- 9036820
TI  - [Pseudo-occlusions of the internal carotid artery].
AB  - The pseudo-occlusion (P.O.) of the internal carotid artery is defined as an
      atheromatous lesion causing a high-grade stenosis, which describes a peculiar
      angiographic finding ("string sing" or "slim sign"). The authors report their
      experience with 6 P.O. (angiographically diagnosed) that had been found in 16
      months. In all these cases, whenever there was a clinical e/or B-scan ultrasound
      suspect, angiographic recommendations for the detection of that lesion have been
      applied. One of these 6 patients, clinically asymptomatic, refused surgery,
      remaining asymptomatic for cerebral ischemia during the successive 16 months;
      angiographic control evidenced an unmodified P.O. The other 5 patients,
      clinically symptomatic, underwent surgical correction: in one, intraoperative
      finding was a total carotid occlusion. In the other 4 patients the P.O. was
      confirmed and an endoarterectomy has been done. No immediate or later
      complications have been noted (clinical and ultrasonographic average follow-up
      time was 12 months). The experience described by the authors leeds to some
      considerations: a) the carotid P.O. is not so rare; specially if adequate
      angiographic technique has been employed; b) the non-invasive studies could not
      reliably distinguish a P.O; c) intraoperative findings do not confirm, always,
      angiographic ones but a fibrous, chronic and totally occluded internal carotid
      artery; d) the evolution of P.O. in a complete carotid occlusion is very probable
      but not obligatory, and if this happens it needs long period of time;
      consequently the surgical correction of P.O. could be justified but not urgently;
      e) the surgical correction of the P.O. can be done without particular difficulty
      and its outcome is so similar to those obtained from the routine carotid surgery.

PMID- 9036821
TI  - [Total thyroidectomy technique: suggestions and proposals of surgical practice].
AB  - Total thyroidectomy at present depicts a diffuse surgical procedure in the
      management of benign and malignant disease of thyroid gland. It is followed by a
      low incidence of iatrogenic damages (nervous lesions or permanent
      hypoparathyroidism), just like subtotal thyroidectomy and lower than surgery for
      nodular recurrences. Authors present the surgical technique they follow to
      perform total thyroidectomy, used in over 400 cases of benign thyroid diseases
      operated since 1986. The most important points of this surgical procedures are
      represented by exposure and sparing of inferior laryngeal nerve and by
      preservation of parathyroid function. Parathyroid glands can be exposed to direct
      surgical trauma but, more often, they are injured by damage of their vascular
      supply. To avoid this complication, vascular ligations of inferior thyroid artery
      have to be done never on the trunk of the artery, but on its branches just near
      the glandular capsula. Sparing of inferior laryngeal nerves comports the exposure
      of this structure for all its cervical course especially in the terminal edge,
      when the nerve is nearest to the gland. Systematical application of illustrated
      procedure has produced no operative mortality, no inferior laryngeal nerve
      permanent palsy, transient hoarseness in 0.5%, and transient symptomatic
      hypocalcemia in 2.7%.

PMID- 9036822
TI  - [Contribution to the knowledge of pseudoneoplastic pathology of the breast. Cyto
      steatonecrosis].
AB  - The authors, from the observation of a case of mammary fat necrosis (BFN),
      observe the problematic nature of this rare pathology, and describe the clinical
      anatomy and the main epidemiological, etiological, radiographical, and
      echographic aspects. They dwell upon the anatomical pathology phase of the
      fibrous substitution and the fibrosclerosis of the liponecrotic area, in which
      the BFN assumes a pseudoneoplastic importance, responsible for a clinical summary
      (hard nodule, of indistinct limits, with frequent cutaneous retractions), a
      radiography (opacity with faded and irregular or spicular outlines, with or
      without the thickening and the retraction of the skin above; stick-like or
      angular dentitrical microcalcifications) an echography ( hypoechogenous nodule
      that may or may not absorb ultrasounds) that are indistinguishable from those of
      a carcinoma, or are difficult to interpret in cases of granulomatous substitution
      not yet evolved into retracted fibrosis. They conclude by emphasizing the role of
      surgical excision biopsy, with an extemporaneous histological examination, the
      results of which decide either the immediate closure of the surgical incision, or
      the adoption of another type of operation.

PMID- 9036823
TI  - [Resection therapy in the treatment of intrahepatic biliary lithiasis].
AB  - The authors report a case of intrahepatic lithiasis in a patient already operated
      of cholecystectomy and without lithiasis of the common bile duct. The lithiasis
      was present in the left lateral bile duct, was multiple and trapped behind a very
      narrow stricture. The stones were associated with a marked dilatation of the
      involved biliary ducts, cholangitis, fibrosis and atrophy of surrounding hepatic
      parenchyma. It was performed a resection of the II and III hepatic segments and
      the patient recovered completely and is well and disease free after one year. The
      authors believe, also on the base of the data reported by others, that in the
      intrahepatic lithiasis with strictures of the bile intrahepatic ducts the hepatic
      resection is the treatment of choice, especially when the lithiasis is present in
      a sectorial or segmental bile duct, preventing any stone recurrence.

PMID- 9036824
TI  - [Study on diagnostic and therapeutic behavior in tumors of the medial-lower third
      of the rectum in 2 Italian regions].
AB  - The authors report about a survey on the behaviour of 51 departments of surgery
      in Lazio and Lombardia as to diagnosis, staging and therapy of carcinoma of the
      medium-lower one-third of the rectum. A set of 722 patients treated in 1993 was
      considered. A questionnaire was distributed and answers collected about the
      staging protocols, the therapeutic choices and some details of surgical technique
      as the ligation of the lower mesenteric artery or the extent of the
      lymphadenectomy. The results indicate some stable trends as to preoperative study
      (digital examination and fibre optic endoscopy in almost all cases) and as to the
      choice of the technique of anastomosis (43.1% of termino-terminal stapled
      anastomosis). Intrarectal ultrasound gains consensus but is still not much
      diffuse (18.6% of cases). Almost all of the participating Institutions agreed in
      joining further prospective studies.

PMID- 9036825
TI  - [Adrenalectomy in metastasis of primary pulmonary carcinoma: an emerging issue].
AB  - Such a novel surgical project is supported by a large basic knowledge on
      molecular biology of solid tumours progression as well as the already assessed
      clinical experience in the parallel field of surgery for lung, brain and liver
      metastases. While pathology and the clinical work up have for a long time pointed
      out the steady rate of adrenal metastatic involvement from lung cancer (from 25
      to 28% of all cases at the autopsy and, on clinical grounds, the most important
      site of extrapulmonary tumour spread just after the first one represented by the
      mediastinal lymphatic groups), the surgical approach to the problem is still very
      limited and the few operated cases previously reported in world literature
      (summing up to a total of 21) are not truly homogeneous and even largely
      scattered in time. The Authors report on their personal contribution in this
      field with four consecutive cases who underwent surgery during the last five
      years. The most important clinical features together with the initial remarkable
      result obtained in one patient who is still free of disease more than 3 years
      after the sequential radical resection of the primary lung tumour and the
      metastatic ipsilateral adrenal gland, are presented. In the light of this
      preliminary positive experience, the Authors are planning a sound clinical
      research based on the combined resection of those NSC Lung Cancers which appear
      surgically resectable but already included in an unresectable Stage IV Disease
      only because of the contemporary adrenal metastases (M1). An adjuvant
      chemotherapy in usually added.

PMID- 9036826
TI  - [Method of biopsy and ultrastructural study of the parathyroid gland in patients
      with primary hyperparathyroidism].
AB  - The authors suggest a new method of biopsy of a seemingly normal human
      parathyroid gland during surgery for parathyroid adenoma. Such a method provides
      adequate surgical specimen to rule out a likely diffuse hyperplastic disease
      associated with the parathyroid adenoma, and for the ultrastructural study of the
      gland, without any risk of postoperative complication. In all patients,
      ultrastructural examination showed an abnormal cell population and signs of
      glandular atrophy as a consequence of the high level of serum calcium due to
      hormonal hyperfunction of the parathyroid adenoma.

PMID- 9036827
TI  - [Bilateral aneurysms of the popliteal artery].
AB  - INTRODUCTION: Popliteal artery aneurysms are the most common of peripheral
      arterial aneurysms. Popliteal aneurysms are bilateral in 42% of patients.
      Atherosclerosis and bacterial invasion of the arterial wall are the predominant
      etiologic factors of popliteal artery aneurysms. CLINICAL CASE: A male of 67
      years old was referred to our institution for bilateral claudication and 150 m.
      free interval. The angiogram showed a partial occluded aneurysm of the right
      popliteal artery and a complete thrombosis of the left popliteal artery
      aneurysms. The left aneurysm was resected and a femoral popliteal by-pass was
      performed, using the inverted saphenous vein graft, associated with left lumbar
      sympathectomy. Six months later the contralateral aneurysm was excised and a
      Dacron femoro-popliteal by-pass graft was performed. Two years later
      Arteriographic and Doppler examination showed patent by-pass bilaterally.
      CONCLUSION: Popliteal artery aneurysms can be a threaten for the lower limbs,
      because of thromboembolic phenomena and occasional rupture. Surgery is the best
      treatment before the appearance of an acute complication and a by-pass with an
      autogenous vein graft or a Dacron graft are the most common surgical procedures
      performed. Thrombolytic therapy offers good results where an acute complication
      appears.

PMID- 9036828
TI  - [Primary cysts of the spleen: a case report].
AB  - The cystic pathology of the spleen is comparatively infrequent and the origin is
      parasitic, hydatid. The parasitic cysts are the 65% of the total and the cysts
      secondary at trauma are the 28%. The real or primary cysts of the spleen are only
      the 75 of the case record. Analyze, in this work, the etiology and the clinic of
      these formations and show the personal experience about a clinical case arrived
      at our observation with negative anamnesis for trauma and with aspecific
      symptomatology like dyspepsia. We think that this notification is useful because
      the cystic primary formations of the spleen are very rare.

PMID- 9036829
TI  - [Mesenteric cysts: etiopathogenetic and clinical considerations and a case
      report].
AB  - According to the literature authors describe the etiopathology and symptoms of a
      case of uncomplicated mesenteric cyst observed and treated by simple enucleation.
      Therefore after describing the peculiarity of this disease, authors underline the
      difficulty of diagnosis also using instrumental devices such as ultrasound and CT
      scan. In particular complicated mesenteric cyst is pointed out because it may be
      responsible of acute abdomen. About treatment of uncomplicated mesenteric cyst
      the always more frequent use of laparoscopy is underlined.

PMID- 9036830
TI  - [Peritoneal mesothelioma. A case report].
AB  - Peritoneal mesothelioma is a rare neoplasm (annual incidence: 1-2 cases per
      million in the general population) and forms about 10% of all mesotheliomas. The
      authors report a case of malignant mesothelioma of the peritoneum in a male, 61
      years old. After laparotomy the patient was treated with intraperitoneal
      administration of cisplatin (40 mg/m2 day 1-2-3-29-30-31) and intravenous
      administration of mitomycin C (10 mg/m2 day 1). The renal toxicity was avoided
      with the GSH and with prehydration before and after administration of the
      cisplatin. The bone marrow toxicity was avoided with the subcutaneous
      administration of G-CSF (300 mg three times each week) and erythropoietin (10.000
      U three times a week). After the first cycle, with the reduction of the ascites,
      the cisplatin was administered intravenously too. After six cycles of
      chemotherapy (18 months after laparotomy) the patient is alive and he has a
      performance status of 1 (ECOG/WHO). The chemotherapy with cisplatin and mitomycin
      C must be preferred to the anthracycline in all the patient with cardiologic
      involvement. The cisplatin administered by intracavitary route give a quick
      response with less systemic toxicity. A review of the literature confirms the
      rarity of this pathology, linked epidemiologically with exposure to asbestos, and
      the difficulty of the preoperative diagnosis: in fact cytologic assay and
      ultrasonographic and TC scan always don't permit to discover a mesothelioma. The
      laparotomy and the laparoscopy are useful in the P.M. for the possibility of the
      biopsies and the apposition of the catheters for intracavitary therapy. The
      response of peritoneal mesothelioma to treatment is poor. The median survival
      after the appearance of the symptom is less than 18 months.

PMID- 9036831
TI  - Multidrug efflux in intrinsic resistance to trimethoprim and sulfamethoxazole in
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa possesses at least two multiple drug efflux systems which
      are defined by the outer membrane proteins OprM and OprJ. We have found that
      mutants overexpressing OprM were two- and eightfold more resistant than their
      wild-type parent to sulfamethoxazole (SMX) and trimethoprim (TMP), respectively.
      For OprJ-overproducing strains, MICs of TMP increased fourfold but those of SMX
      were unchanged. Strains overexpressing OprM, but not those overexpressing OprJ,
      became hypersusceptible to TMP and SMX when oprM was inactivated. The wild-type
      antibiotic profile could be restored in an oprM mutant by transcomplementation
      with the cloned oprM gene. These results demonstrate that the mexABoprM multidrug
      efflux system is mainly responsible for the intrinsic resistance of P. aeruginosa
      to TMP and SMX.

PMID- 9036832
TI  - Proceedings of the 2nd International Workshop on Lantibiotics. Arnhem, The
      Netherlands, 20-23 November 1994.

PMID- 9036834
TI  - Shaping the future.

PMID- 9036833
TI  - Suture conversion without the knots.

PMID- 9036835
TI  - Australian general practice in the year 2000.

PMID- 9036836
TI  - Taming the information jungle.

PMID- 9036837
TI  - [Model systems based on the lipid-porphyrin assemblies and lipoproteins in
      biochemical studies].
AB  - Reviewed are the modern state and prospects of using lipid-porphyrin assemblies
      and lipoporphyrins to study fine functional mechanisms of complex biological
      systems and to solve applied problems in biochemistry and medicine. Data on the
      interaction of porphyrin derivatives with natural and artificial membranes are
      summarized. Models for electron transfer and oxygen transport via lipid-porphyrin
      assemblies are discussed.

PMID- 9036838
TI  - [Biologically active myo-inositol phosphates].
AB  - The main problems and results of synthetic studies of biologically important myo
      inositol phosphates were discussed. The development of the methods of synthesis
      was shown, and current trends in the methodology of obtaining myo-inositol
      phosphates by chemical methods were considered.

PMID- 9036839
TI  - [Modified nucleoside phosphates as precursors of antineoplastic and antiviral
      compounds in a cell].

PMID- 9036840
TI  - [Synthesis of cationic alkylglucosides].

PMID- 9036842
TI  - [3-(1H-indol-3-yl)-4-(1-glykozylindol-3-yl)-1H-pyrrole-2,5-diones: synthesis and
      study of antiproliferative properties].
AB  - A synthesis of 3-(1H-3-indolyl)-4-(1-glycosyl-3-indolyl)furan-2,5-diones and -1H
      pyrrole-2,5-diones modified with the residues of D-ribo-, D-xylo-, L-arabino-, D
      galactopyranose, and D-lactose was described. Influence of the compounds prepared
      on DNA biosynthesis in CaOv cells was studied.

PMID- 9036841
TI  - [Stereochemistry of substituting the allyl hydroxyl group with fluorine atom in
      prostaglandins. Synthesis of 15-fluoro-11,15-dideoxyprostaglandins E1].
AB  - (+/-)-15-Fluoro-11,15-dideoxyprostaglandin E1 and its methyl and ethyl esters
      were synthesized. Dehydroxyfluorination reaction (+/-)-11-deoxyprostaglandin E1
      esters with various reagents based on SF4 was studied. Along with the target 15
      fluorides (mixtures of alpha- and beta-epimers), products of allylic shift and
      dehydration in a ratio dependent on the fluorination agent were shown to be
      formed. With a morpholinotrifluorosulfuran-tris(morpholine)sulfonium
      trimethyldifluorosilicate mixture, the maximal excess (70%) of one of the 15
      fluoro epimers was achieved. Possible mechanisms of dehydroxyfluorination of (+/
      )-11-deoxyprostaglandin E1 esters with dialkylaminoflluorosulfurans were
      proposed. Methyl esters of 15-alpha-fluoro- and 15-beta-fluoro-11,15
      dideoxyprostaglandin E1 exhibited moderate antiaggregation activity in rabbit
      platelet tests.

PMID- 9036843
TI  - [Relation between the conformation and antioxidant properties in a series of
      topochemical analogs of carnosine and carcinine with different N-acyl
      substitutes].
AB  - To elucidate the influence of the nature of N-acyl substituent on antioxidant
      properties of carcinine analogs, the corresponding histamine derivatives were
      synthesized. Antioxidant activity of the compounds prepared was investigated in
      the Fe(2+)-ascorbate-dependent system of oxidation of the linoleic acid micellar
      solution. Conformations of carnosine, carcinine, and their analogs were
      calculated by the molecular mechanics MM+ method. The structural elements and
      conformations that are preferable for the appearance of antioxidant activity were
      found.

PMID- 9036844
TI  - [Physico-chemical properties of liposome forms of L-3,4-dihydroxyphenylalanine
      (DOPA) and dopamine].
AB  - L-3,4-Dihydroxyphenylalanine (DOPA) and dopamine encapsulated in liposomes have
      been obtained. These preparations can be used as drugs for Parkinson's disease.
      The level of encapsulation of the compounds under study in liposomes and their
      partition coefficients have been determined. The kinetics of DOPA (or dopamine)
      exit from the liposomes have been studied.

PMID- 9036845
TI  - [Precipitation of cytochromes c with complex cadmium iodide].
AB  - Using cytochrome c from horse heart and the yeast candida valida as examples, it
      was shown that a complex anion, cadmium tetraiodide (CdI42-), precipitated
      proteins from aqueous solutions at the reagent concentrations below 50 mM. The
      composition and pH value of the solution, as well as the starting protein
      concentration, considerably influenced the precipitation. The results suggest
      that this reagent acts on the protein by a mechanism similar to the salting-out
      process. The ability to act at small concentrations is the advantage of CdI42-
      over conventional agents.

PMID- 9036846
TI  - Diring Yuriakh: A lower paleolithic site in central Siberia.
AB  - Lower Paleolithic artifacts have been recovered from a single occupation surface
      within stratified deposits at Diring Yuriakh, an archaeological site in central
      Siberia. Thermoluminescence age estimates from eolian sediments indicate that the
      cultural horizon is greater than 260,000 years old. Diring Yuriakh is an order of
      magnitude older than documented Paleolithic sites in Siberia and is important for
      understanding the timing of human expansion into the far north, early adaptations
      to cold climates, and the peopling of the Americas.

PMID- 9036847
TI  - Laser Rapid Prototyping of Photonic Band-Gap Microstructures
AB  - Three-dimensional periodic microstructures of aluminum oxide, which are important
      for creating photonic band-gap structures (PBGs), were fabricated by laser rapid
      prototyping by means of laser-induced direct-write deposition from the gas phase.
      The structures consisted of layers of parallel rods forming a face-centered
      tetragonal lattice with lattice constants of 66 and 133 micrometers. These
      structures showed transmission minima centered around 4 terahertz (75
      micrometers) and 2 terahertz (150 micrometers), respectively. PBGs will allow
      precise control of the optical properties of materials, including lasers without
      threshold.

PMID- 9036848
TI  - Low-Temperature Nonoxidative Activation of Methane over H-Galloaluminosilicate
      (MFI) Zeolite
AB  - Conversion of methane to higher hydrocarbons by its low-temperature activation
      without forming undesirable carbon oxides is of great scientific and practical
      importance. Methane can be highly activated, yielding high rates of conversion to
      higher hydrocarbons and aromatics (10 to 45 percent) at low temperatures
      (400&deg; to 600&deg;C), by its reaction over H-galloaluminosilicate ZSM-5 type
      (MFI) zeolite in the presence of alkenes or higher alkanes. The methane
      activation results from its hydrogen-transfer reaction with alkenes.

PMID- 9036849
TI  - Dissociation of methane into hydrocarbons at extreme (planetary) pressure and
      temperature.
AB  - Constant-pressure, first-principles molecular dynamic simulations were used to
      investigate the behavior of methane at high pressure and temperature. Contrary to
      the current interpretation of shock-wave experiments, the simulations suggest
      that, below 100 gigapascals, methane dissociates into a mixture of hydrocarbons,
      and it separates into hydrogen and carbon only above 300 gigapascals. The
      simulation conditions (100 to 300 gigapascals; 4000 to 5000 kelvin) were chosen
      to follow the isentrope in the middle ice layers of Neptune and Uranus.
      Implications on the physics of these planets are discussed.

PMID- 9036850
TI  - Burst Conditions of Explosive Volcanic Eruptions Recorded on Microbarographs
AB  - Explosive volcanic eruptions generate pressure disturbances in the atmosphere
      that propagate away either as acoustic or as shock waves, depending on the
      explosivity of the eruption. Both types of waves are recorded on microbarographs
      as 1- to 0.1-hertz N-shaped signals followed by a longer period coda. These
      waveforms can be used to estimate burst pressures and gas concentrations in
      explosive volcanic eruptions and provide estimates of eruption magnitudes.

PMID- 9036851
TI  - Deciding advantageously before knowing the advantageous strategy.
AB  - Deciding advantageously in a complex situation is thought to require overt
      reasoning on declarative knowledge, namely, on facts pertaining to premises,
      options for action, and outcomes of actions that embody the pertinent previous
      experience. An alternative possibility was investigated: that overt reasoning is
      preceded by a nonconscious biasing step that uses neural systems other than those
      that support declarative knowledge. Normal participants and patients with
      prefrontal damage and decision-making defects performed a gambling task in which
      behavioral, psychophysiological, and self-account measures were obtained in
      parallel. Normals began to choose advantageously before they realized which
      strategy worked best, whereas prefrontal patients continued to choose
      disadvantageously even after they knew the correct strategy. Moreover, normals
      began to generate anticipatory skin conductance responses (SCRs) whenever they
      pondered a choice that turned out to be risky, before they knew explicitly that
      it was a risky choice, whereas patients never developed anticipatory SCRs,
      although some eventually realized which choices were risky. The results suggest
      that, in normal individuals, nonconscious biases guide behavior before conscious
      knowledge does. Without the help of such biases, overt knowledge may be
      insufficient to ensure advantageous behavior.

PMID- 9036852
TI  - Single Molecule Force Spectroscopy on Polysaccharides by Atomic Force Microscopy
AB  - Recent developments in piconewton instrumentation allow the manipulation of
      single molecules and measurements of intermolecular as well as intramolecular
      forces. Dextran filaments linked to a gold surface were probed with the atomic
      force microscope tip by vertical stretching. At low forces the deformation of
      dextran was found to be dominated by entropic forces and can be described by the
      Langevin function with a 6 angstrom Kuhn length. At elevated forces the strand
      elongation was governed by a twist of bond angles. At higher forces the dextran
      filaments underwent a distinct conformational change. The polymer stiffened and
      the segment elasticity was dominated by the bending of bond angles. The
      conformational change was found to be reversible and was corroborated by
      molecular dynamics calculations.

PMID- 9036853
TI  - Macromolecular trafficking indicated by localization and turnover of sucrose
      transporters in enucleate sieve elements.
AB  - The leaf sucrose transporter SUT1 is essential for phloem loading and long
      distance transport of assimilates. Both SUT1 messenger RNA (mRNA) and protein
      were shown to be diurnally regulated and to have high turnover rates. SUT1
      protein was detected by immunolocalization in plasma membranes of enucleate sieve
      elements (SEs) in tobacco, potato, and tomato. Analysis by in situ hybridization
      showed that SUT1 mRNA localizes mainly to the SE and is preferentially associated
      with plasmodesmata. Antisense inhibition of SUT1 expression under control of a
      companion cell (CC)-specific promoter indicated synthesis of SUT1 mRNA in the CC.
      These results provide evidence for targeting of plant endogenous mRNA and
      potentially SUT1 protein through phloem plasmodesmata and for sucrose loading at
      the plasma membrane of SE.

PMID- 9036854
TI  - Control of vertebrate left-right asymmetry by a snail-related zinc finger gene.
AB  - A gene encoding a zinc finger protein of the Snail family, cSnR, is expressed in
      the right-hand lateral mesoderm during normal chick development. Antisense
      disruption of cSnR function during the hours immediately preceding heart
      formation randomized the normally reliable direction of heart looping and
      subsequent embryo torsion. Implanted ectopic sources of intercellular signal
      proteins that are involved in establishing normal left-right information
      randomized the handedness of heart development and also altered the asymmetry of
      cSnR expression. cSnR thus appears to act downstream of these signals, or perhaps
      in parallel with the latest expressed of them, the Nodal protein, in controlling
      the anatomical asymmetry.

PMID- 9036855
TI  - Crystal structure of formate dehydrogenase H: catalysis involving Mo,
      molybdopterin, selenocysteine, and an Fe4S4 cluster.
AB  - Formate dehydrogenase H from Escherichia coli contains selenocysteine (SeCys),
      molybdenum, two molybdopterin guanine dinucleotide (MGD) cofactors, and an Fe4S4
      cluster at the active site and catalyzes the two-electron oxidation of formate to
      carbon dioxide. The crystal structures of the oxidized [Mo(VI), Fe4S4(ox)] form
      of formate dehydrogenase H (with and without bound inhibitor) and the reduced
      [Mo(IV), Fe4S4(red)] form have been determined, revealing a four-domain alphabeta
      structure with the molybdenum directly coordinated to selenium and both MGD
      cofactors. These structures suggest a reaction mechanism that directly involves
      SeCys140 and His141 in proton abstraction and the molybdenum, molybdopterin,
      Lys44, and the Fe4S4 cluster in electron transfer.

PMID- 9036856
TI  - Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase.
AB  - The small guanosine triphosphatase (GTPase) Rho is implicated in the formation of
      stress fibers and focal adhesions in fibroblasts stimulated by extracellular
      signals such as lysophosphatidic acid (LPA). Rho-kinase is activated by Rho and
      may mediate some biological effects of Rho. Microinjection of the catalytic
      domain of Rho-kinase into serum-starved Swiss 3T3 cells induced the formation of
      stress fibers and focal adhesions, whereas microinjection of the inactive
      catalytic domain, the Rho-binding domain, or the pleckstrin-homology domain
      inhibited the LPA-induced formation of stress fibers and focal adhesions. Thus,
      Rho-kinase appears to mediate signals from Rho and to induce the formation of
      stress fibers and focal adhesions.

PMID- 9036857
TI  - APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle.
AB  - The molecular mechanisms that link cell-cycle controls to the mitotic apparatus
      are poorly understood. A component of the Saccharomyces cerevisiae spindle, Ase1,
      was observed to undergo cell cycle-specific degradation mediated by the
      cyclosome, or anaphase promoting complex (APC). Ase1 was degraded when cells
      exited from mitosis and entered G1. Inappropriate expression of stable Ase1
      during G1 produced a spindle defect that is sensed by the spindle assembly
      checkpoint. In addition, loss of ASE1 function destabilized telophase spindles,
      and expression of a nondegradable Ase1 mutant delayed spindle disassembly. APC
      mediated proteolysis therefore appears to regulate both spindle assembly and
      disassembly.

PMID- 9036858
TI  - Combinatorial control required for the specificity of yeast MAPK signaling.
AB  - In yeast, an overlapping set of mitogen-activated protein kinase (MAPK) signaling
      components controls mating, haploid invasion, and pseudohyphal development.
      Paradoxically, a single downstream transcription factor, Ste12, is necessary for
      the execution of these distinct programs. Developmental specificity was found to
      require a transcription factor of the TEA/ATTS family, Tec1, which cooperates
      with Ste12 during filamentous and invasive growth. Purified derivatives of Ste12
      and Tec1 bind cooperatively to enhancer elements called filamentation and
      invasion response elements (FREs), which program transcription that is
      specifically responsive to the MAPK signaling components required for filamentous
      growth. An FRE in the TEC1 promoter functions in a positive feedback loop
      required for pseudohyphal development.

PMID- 9036859
TI  - Role of transforming growth factor-beta in long-term synaptic facilitation in
      Aplysia.
AB  - The role of transforming growth factor-beta (TGF-beta) in long-term synaptic
      facilitation was examined in isolated Aplysia ganglia. Treatment with TGF-beta1
      induced long-term facilitation (24 and 48 hours), but not short-term (5 to 15
      minutes) or intermediate-term (2 to 4 hours) facilitation. The long-term effects
      of TGF-beta1 were not additive with those of serotonin. Moreover, serotonin
      induced facilitation was blocked by an inhibitor of TGF-beta. Thus, activation of
      TGF-beta may be part of the cascade of events underlying long-term sensitization,
      consistent with the hypothesis that signaling molecules that participate in
      development also have roles in adult neuronal plasticity.

PMID- 9036860
TI  - Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5.
AB  - A complementary DNA clone has been isolated that encodes a coxsackievirus and
      adenovirus receptor (CAR). When transfected with CAR complementary DNA,
      nonpermissive hamster cells became susceptible to coxsackie B virus attachment
      and infection. Furthermore, consistent with previous studies demonstrating that
      adenovirus infection depends on attachment of a viral fiber to the target cell,
      CAR-transfected hamster cells bound adenovirus in a fiber-dependent fashion and
      showed a 100-fold increase in susceptibility to virus-mediated gene transfer.
      Identification of CAR as a receptor for these two unrelated and structurally
      distinct viral pathogens is important for understanding viral pathogenesis and
      has implications for therapeutic gene delivery with adenovirus vectors.

PMID- 9036861
TI  - Expression of high-mobility group-1 mRNA in human gastrointestinal adenocarcinoma
      and corresponding non-cancerous mucosa.
AB  - An 1194-nucleotide complementary DNA clone, FM1, encoding a human high-mobility
      group-1 protein (HMG-1) was isolated from a well-differentiated human gastric
      carcinoma cell line complementary DNA library by a differential screening method.
      FM1 is similar to the published human HMG-1 in mature protein, with only 3
      different codons at positions 11, 149, and 190. We analyzed 33 gastric and
      colorectal adenocarcinomas for expression of the FM1 gene. Northern-blot analysis
      revealed that all of the cancers expressed FM1 at a higher level than in
      corresponding non-cancerous mucosa, with 2 transcripts of approximately 1.4 and
      2.4 kilobases. The FM1 expression level in the non-cancerous tissues increased
      with the depth of accompanying cancer invasion. Only 18.2% of well-differentiated
      cancers showed a higher expression level in corresponding non-cancerous tissues,
      whereas the expression in corresponding non-cancerous tissues was significantly
      higher in moderately (60%) and poorly differentiated (83.3%) cancers. In situ
      hybridization demonstrated the location of FM1 mRNA in well- and poorly
      differentiated gastric-cancer cells as well as in non-cancerous tissue adjacent
      to poorly differentiated gastric cancer, but no hybridization was detected in
      normal epithelial cells adjacent to well-differentiated gastric cancer. These
      findings may provide new information on HMG-1 mRNA expression in human
      gastrointestinal cancer and suggest a correlation between FM1 mRNA expression to
      the differentiation and the stage of human gastrointestinal adenocarcinomas.

PMID- 9036862
TI  - Metanestin, a glycoprotein with metastasis-associated expression in transitional
      cell carcinoma of the urinary bladder.
AB  - A 60-kDa glycoprotein named metanestin was identified by molecular cloning. The
      glycoprotein had a twice-repeated motif of Pro-Gly-Pro-Gly and carried metastasis
      associated carbohydrate epitopes. The antibody to the protein portion of
      metanestin strongly reacted with lymph-node metastasis of transitional-cell
      carcinoma of the urinary bladder, but the reactivity to the primary tumor was
      generally weaker and the normal urothelium was scarcely reactive. Thus both
      metanestin and the carbohydrate on it showed metastasis-associated expression. In
      addition, we identified a 100-kDa glycoprotein with a 4-times-repeated motif of
      Pro-Ala-Pro-Ala. The antibody to the 100-kDa glycoprotein showed reactivity
      similar to that to metanestin.

PMID- 9036863
TI  - Decreased expression of biliary glycoprotein in hepatocellular carcinomas.
AB  - Biliary glycoprotein (BGP) is an adhesion and anti-cell-growth molecule of the
      carcinoembryonic antigen family. We have earlier demonstrated that BGP mRNA is
      expressed in hepatocellular carcinomas (HCCs) and the adjacent non-cancerous
      regions, neither of which express CEA and NCA mRNA. To define an expression level
      and pattern of BGP at the protein level in HCCs, TS135, a monoclonal antibody
      (MAb) against BGP, was prepared. This MAb clearly reacted with BGP with a
      molecular weight of 110 kDa and 85 kDa (BGP-110/85). It cross-reacted weakly with
      NCA-90 from NCA transfectants, but not at all with CEA-200 from the serum of a
      colon-cancer patient. The BGP transfectants of cultured hepatocellular carcinoma
      cHc-4 cells showed Ca2+-dependent cell aggregation, which was partially inhibited
      by modulating BGP on the cell surface with MAb TS135. Immunostaining of non
      cancerous liver tissues with MAb TS135 indicated that BGP could be expressed in
      the bile canalicular domain of hepatocytes. In HCCs, the expression of BGP was
      predominantly found in the well-differentiated type, where the bile canaliculi
      and the apical portion of pseudoglands were positively stained, although their
      staining intensity and stained area were lower and more limited, respectively,
      than those of non-cancerous regions. The percentage of faintly positive and
      negative cases (n = 22) from the total (n = 30) was 73%. This suggests that the
      expression level of BGP decreased in HCCs as compared with adjacent non-cancerous
      regions.

PMID- 9036864
TI  - Intracellular carotenoid levels measured by Raman microspectroscopy: comparison
      of lymphocytes from lung cancer patients and healthy individuals.
AB  - Most studies concerning a possible protective role of carotenoids against cancer
      focus on serum carotenoid levels. We have used Raman microspectroscopy to study
      the intracellular amounts of carotenoids in lymphocytes of lung cancer patients
      and of healthy individuals. Our results indicate a significant decrease of
      carotenoids in lung carcinoma patients compared with healthy individuals,
      particularly in adenocarcinoma patients. Carotenoid supplementation raised the
      serum concentration in 2 lung cancer patients up to normal levels, whereas
      intracellular content remained significantly lower. This indicates that
      carotenoid uptake by lymphocytes is not only dependent on serum carotenoid
      concentration. Our findings indicate that Raman microspectroscopy, a recently
      developed technique to measure intracellular levels of drugs, is also well suited
      to obtain quantitative data on carotenoid amounts inside cells.

PMID- 9036865
TI  - p16/CDKN2 and CDK4 gene mutations in sporadic melanoma development and
      progression.
AB  - The p16/CDKN2(MTS1) gene encoding for the p16 inhibitor of cyclin D/CDK4
      complexes is frequently mutated and deleted in a large fraction of melanoma cell
      lines, and p16 germline mutations have also been observed in familial melanomas.
      Moreover, a CDK4 gene mutation, responsible for a functional resistance of CDK4
      kinase to p16 inhibitory activity, has been described to occur in some cases of
      familial melanoma. These data strongly support the idea that deregulation of the
      CDK4/cyclin D pathway, via CDKN2 or CDK4 mutations, is of biological significance
      in the development of melanoma. To shed light on the role of these alterations in
      the development and progression of sporadic melanoma, 12 primary melanomas and 9
      corresponding metastases were analyzed for CDKN2 and CDK4 gene mutations. Of the
      12 primary melanomas analyzed, 4 showed the presence of mutational inactivation
      of the p 16 protein and 2 carried silent mutations. No metastases showed the
      presence of CDKN2 mutations, indicating that mutations of this cyclin-dependent
      kinase inhibitor is not common in the progression of sporadic melanoma. On the
      other hand, the absence, in the metastases, of the CDKN2 mutation detected in the
      corresponding primary tumors suggests that 9p21 homozygous deletion may play a
      major role in the metastatic spreading of this type of tumor. None of the cases
      analyzed showed the presence of an Arg24Cys mutation, which functionally protects
      CDK4 from p16 inhibition. This indicates that CDK4 mutation plays a minor role in
      the development and progression of sporadic melanoma.

PMID- 9036866
TI  - Serological evidence of an association between Chlamydia pneumoniae infection and
      lung cancer.
AB  - Epidemiological evidence suggests that airway obstruction is an independent risk
      factor for lung cancer and that this cannot be explained by active or passive
      smoking alone. Chlamydia pneumoniae infection has been associated with chronic
      bronchitis and its exacerbates. Our aim was to evaluate the association between
      chronic C. pneumoniae infection and risk of lung cancer among male smokers.
      Smoking males with lung cancer (n = 230) and their age- and locality-matched
      controls were selected among participants of the Alpha-Tocopherol, Beta-Carotene
      Cancer Prevention Study. The presence of C. pneumoniae infection was assessed by
      analyzing specific antibodies and immune complexes in 2 serum samples collected
      with a 3-year interval before the lung cancer diagnosis. The diagnosis of chronic
      infection was based on stable levels of positive specific IgA antibody (titer >
      or = 16) and immune complex (titer > or = 4). Relative risks were estimated by
      odds ratios (OR) adjusted for age, locality and smoking history by a conditional
      logistic regression model. Markers suggesting chronic C. pneumoniae infection
      were present in 52% of cases and 45% of controls and hence were positively
      associated with the incidence of lung cancer (OR 1.6; 95% confidence interval
      [CI] 1.0-2.3). The incidence was especially increased in men younger than 60
      years (OR 2.9; 95% CI 1.5-5.4) but not in the older age group (OR 0.9; 95% CI 0.5
      1.6). Before concluding that C. pneumoniae infection is a new independent risk
      factor for lung cancer, corroboration from other studies with larger number of
      cases and longer follow-up is needed.

PMID- 9036867
TI  - Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and
      Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal
      carcinogenesis.
AB  - Defining the molecular mechanisms involved in cancer formation and progression is
      still a major challenge in colorectal-cancer research. Our strategy was to
      characterize genes whose expression is altered during colorectal carcinogenesis.
      To this end, the phenotype of a colorectal tumour was previously established by
      partial sequencing of a large number of its transcripts and the genes of interest
      were selected by differential screening on high-density filters with mRNA of
      colorectal cancer and normal adjacent mucosa. Fifty-one clones were found over
      expressed and 23 were underexpressed in the colorectal-cancer tissues of the 5
      analyzed patients. Among the latter, clones 6G2 and 32D6 were found of particular
      interest, since they had significant homology with several homeodomain-containing
      genes. The highest degree of similarity was with the murine Cdx1 for 6G2, and
      with the murine Cdx2 and hamster Cdx3 for 32D6. Using a RT-PCR approach, complete
      sequence of both types of homeobox-containing cDNA was obtained. The amino-acid
      sequence of the human Cdx1 is 85% identical to the mouse protein, and human Cdx2
      has 94% identity with the mouse Cdx2 and hamster Cdx3. Tissue-distribution
      analysis of Cdx1 and Cdx2 mRNA showed that both transcripts were specifically
      expressed in small intestine, in colon and rectum. Twelve tissue samples from
      colorectal adenocarcinomas and the corresponding normal mucosa were analyzed by
      Northern blot. Expression of the 2 types of mRNA was either reduced or absent in
      10 of them. Several colon-cancer cell lines were also analyzed. Cdx2 mRNA was
      absent from LS174T cells and Cdx1 mRNA was absent in PF11, TC7 and SW480 cells;
      none was detected in HT29 cells. It was concluded that decrease in human Cdx1
      and/or Cdx2 expression is associated with colorectal tumorigenesis.

PMID- 9036868
TI  - Deletion of three distinct regions on chromosome 13q in human non-small-cell lung
      cancer.
AB  - We examined loss of heterozygosity (LOH) at the retinoblastoma susceptibility
      gene (RB1) locus on chromosome 13q14 in 20 non-small-cell lung cancers (NSCLCs)
      using polymorphic markers. The expression of RB protein was examined by
      immunohistochemical analysis of paraffin-embedded specimens of the same tumors.
      The results revealed that 10 of 16 informative cases showed an LOH at the RB1
      locus, whereas only 2 of the 10 tumors lost expression of the RB protein. These 2
      tumors had mutations in the remaining RB1 allele. Thus, inactivation of the RB1
      gene appears to be involved in a small subset of NSCLCs only. To elucidate the
      presence of tumor-suppressor genes other than RB1 on 13q, heterozygosity at 15
      different loci was investigated. Of 20 tumors analyzed, 15 showed an LOH at least
      at one locus, and the regions 13q12.1-qter, 13q12.2-14.2 and 13q14.1-q14.3,
      including the RB1 locus, were deleted in significant numbers of the tumors. Our
      results suggest that, in addition to the RB1 gene, abnormalities of other tumor
      suppressor genes on chromosome 13q are involved in the development of human
      NSCLCs.

PMID- 9036869
TI  - Association of human papillomavirus type 16 integration in the E2 gene with poor
      disease-free survival from cervical cancer.
AB  - To determine the clinical relevance of human papillomavirus (HPV) integration and
      E2 function suggested by in vitro studies, we investigated 50 patients with HPV
      16-positive primary cervical carcinoma (stage Ib-IV) diagnosed and treated at one
      institution. The physical state of HPV was determined by colorimetric in situ
      hybridization and was not found to vary by stage. Overall, 62% of tumors had
      integrated HPV, 16% had episomal and 22% had both integrated and episomal. The
      E1/E2 region was evaluated by 8 separate polymerase chain reactions, which
      resulted in overlapping products. There was no significant variation in ability
      to amplify the E1/E2 region with stage. E1/E2 amplification correlated with
      physical state. Nearly all tumors with episomal or mixed HPV 16 DNA amplified all
      8 E1/E2 fragments. Half of the tumors with integrated HPV 16 DNA failed to
      amplify one or more E1/E2 fragments. Disruptions were most frequent in the E2
      region. For all 46 patients receiving curative therapy, the Kaplan-Meier estimate
      of disease-free survival was determined for those whose primary tumors had
      amplifiable E2 compared with those lacking one or more E2 DNA fragments.
      Disruption of E2 was associated with significantly shortened disease-free
      survival.

PMID- 9036870
TI  - Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product
      P16INK4A in ovarian cancer is associated with progression and unfavourable
      prognosis.
AB  - Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant
      and 31 benign epithelial tumours, were analysed immunohistochemically for
      expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A
      (p16). Most benign tumours showed no p16 expression in the tumour cells, whereas
      only 11% of malignant cancers were p16 negative. A high proportion of p16
      positive tumour cells was associated with advanced stage and grade, and with poor
      prognosis in cancer patients. For FIGO stage I tumours, a high proportion of p16
      positive tumour cells was associated with poorer survival, suggesting that
      accumulation of p16 is an early event of ovarian tumorigenesis. In contrast to
      tumour cells, high expression of p16 in the surrounding stromal cells was not
      associated with the stage and grade, but was associated with longer survival.
      When all parameters were combined in a multivariate analysis, high p16 expression
      in stromal cells was not an independent predictor for survival, indicating that
      low p16 expression in stromal cells is associated with other markers of tumour
      progression. High expression of p16 in the stromal cells of tumours from long
      term survivors suggests that tumour growth is limited to some extent by factors
      associated with p16 expression in the matrix.

PMID- 9036871
TI  - Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in
      squamous cell lung cancer.
AB  - Tumor specimens from 109 patients with previously untreated squamous cell lung
      carcinomas were analyzed immunohistologically for the expression of vascular
      endothelial growth factor (VEGF) and its receptor Flt-1. Our analysis attempted
      to determine whether these factors have additional prognostic value for the
      patients' survival. VEGF staining was seen in 59% and Flt-1 staining in 68% of
      the cases. No significant correlations were detected between VEGF or Flt-1
      expression and stage or metastasis. Patients with VEGF-stained tumors had
      significantly lower survival times than patients with negative tumors. Expression
      of Flt-1 showed no significant correlation with survival. Combining VEGF and Flt
      1 expressions did not improve the prognostic value. Multivariate analysis showed
      that metastasis and VEGF expression are significant and independent prognostic
      factors for the survival of patients with squamous cell lung carcinomas.

PMID- 9036872
TI  - Increased recurrence and metastasis in patients whose primary head and neck
      squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating
      factor and contained CD34+ natural suppressor cells.
AB  - Human head and neck squamous cell carcinomas (HNSCC) that produce high levels of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to
      contain CD34+ natural suppressor cells that inhibit the activity of intratumoral
      T-cells. The present study evaluated whether GM-CSF production and the presence
      of CD34+ cells within primary HNSCC would translate into increased recurrence,
      metastasis or cancer-related death during the 2 years following surgical
      excision. Freshly excised primary HNSCC of 20 patients that subsequently
      developed disease, and of 17 patients that remained with no evidence of disease
      were analyzed for production of GM-CSF and for CD34+ cell content. The cancers of
      patients that subsequently developed recurrences or metastatic disease produced
      almost 4-fold the levels of GM-CSF and had approximately 2.5-fold the number of
      CD34+ cells as did cancers of patients that remained disease-free. In a second
      method of analysis, the prognostic significance of high vs. low GM-CSF and CD34+
      cell values was evaluated. These analyses showed that patients whose cancers
      produced high GM-CSF levels or had a high CD34+ cell content had a
      disproportionately high incidence of recurrence or metastatic disease (94% and
      100%, respectively), while the majority of patients whose primary cancers
      produced low levels of GM-CSF or had a low CD34+ cell content remained disease
      free (16% and 19%, respectively). Our results indicate that the presence of CD34+
      cells in GM-CSF-producing HNSCC is associated with a poorer prognosis for the
      cancer patients and suggest the utility of these parameters as prognostic
      indicators of outcome. Mechanistically, our results suggest that the presence of
      immune suppressive CD34+ cells in GM-CSF-producing HNSCC leads to increased tumor
      recurrence or metastasis.

PMID- 9036873
TI  - Detection of squamous-cell carcinoma antigen-expressing tumour cells in blood by
      reverse transcriptase-polymerase chain reaction in cancer of the uterine cervix.
AB  - We used a reverse transcriptase-polymerase chain reaction method for squamous
      cell carcinoma (SCC) antigen mRNA to detect circulating tumour cells in patients
      with carcinoma of the uterine cervix. The sensitivity of the method, as
      determined by cell spiking experiments, was 10 cultured A431 cells among 10(6)
      white blood cells. Circulating tumour cells were detected in 6 of 15 patients. In
      our control group of 24 women, SCC antigen mRNA was detected in 2 pregnant women
      at term. We followed up the patients for 24 months after sampling and evaluated
      the outcome. Three out of 6 patients positive for SCC antigen mRNA have relapsed.
      Additionally, 1 patient has developed breast cancer. In the group of 9 patients
      negative for SCC antigen mRNA there has been 1 relapse and 1 case of progression
      of disease. These results suggest that detection of SCC antigen mRNA in
      peripheral blood by RT-PCR could be useful for staging and evaluation of
      prognosis in epidermoid carcinoma of the uterine cervix.

PMID- 9036874
TI  - Microvessel density in unknown primary tumors.
AB  - Unknown primary tumors (UPT) are characterized by early and widespread
      metastasis. There is a strong indication that angiogenesis measured as
      microvessel density (MVD) correlates with the incidence of metastases in several
      solid tumors. The objective of this study was to compare MVD in liver metastases
      of UPT with MVD in known primaries and in liver metastases of colon and breast
      tumors and to investigate the prognostic significance of MVD in UPT. The clinical
      data and the MVD in liver metastases of 39 consecutive patients with UPT
      adenocarcinomas were studied. For comparison, MVD in the primary tumor and in
      liver metastases from known primary adenocarcinomas of the colon (n = 24) and the
      breast (n = 6) were measured. Most of the pathological material was obtained by
      needle biopsy. MVD was determined on formalin-fixed, paraffin-embedded
      histological sections of liver metastases, using the CD34 and von Willebrand
      Factor (vWF) antibodies and immunocytochemistry. The association of MVD with age,
      gender, number of metastases and tumor differentiation was assessed in the UPT
      population. The prognostic value of clinical variables and of MVD on survival was
      estimated by univariate and multivariate regression analysis. There was no
      difference between the MVD in liver metastases of UPT and known primaries. The
      MVD counts in the primary tumors of colon and breast were, however, significantly
      higher than in the metastases. MVD counts correlated well between anti-CD34 and
      anti-vWF. Within the UPT population there was no association between MVD and age,
      gender, number of metastases and tumor differentiation. The MVD was the only
      prognostic factor for survival in univariate analysis. High MVD was correlated
      with short survival. In the multivariate analysis, the number of metastases,
      tumor differentiation, therapy and MVD were all prognostic indicators for
      survival.

PMID- 9036875
TI  - Primary small-cell lung carcinomas and their metastases are characterized by a
      recurrent pattern of genetic alterations.
AB  - Small-cell lung cancer (SCLC) represents a group of highly malignant tumors
      giving rise to early and widespread metastases. We used comparative genomic
      hybridization in autoptic tumor specimens from 10 patients to discover genetic
      alterations that are associated with tumor progression and potentially with the
      metastatic phenotype. Ten primary SCLC and 16 corresponding metastases were
      investigated with a maximum of 4 tumors per case. Prevalent changes observed in
      more than 60% of the primary tumors and their metastases included deletions on
      chromosomes 3p, 4q, 5q, 10q, 13q and 17p, and DNA over-representations on
      chromosomes 3q and 5p. The number of common alterations in the primary tumors and
      the related metastases outnumbered the differences, indicating a clonal
      relationship. Within the lesions of the same patient, differences were found
      between the primary tumor and the metastases as well as between metastases of
      distinct organ sites. However, no specific alteration was significantly
      associated with the metastatic phenotype. We suggest that the high malignancy of
      SCLC is defined by the above-mentioned pattern of aberrations.

PMID- 9036876
TI  - K-ras and p53 mutations in hereditary non-polyposis colorectal cancers.
AB  - Genetic instability related to defective DNA mismatch repair genes may be
      involved in the pathogenesis of carcinoma in Hereditary Non-Polyposis Colorectal
      Cancer (HNPCC). To test that the targets of genetic instability could include
      critical transforming genes involved in colon tumor progression, we examined 23
      colorectal carcinomas in patients with HNPCC in order to detect somatic mutations
      in K-ras and p53 genes. Using single strand conformation polymorphism followed by
      direct DNA sequencing, we detected 4 mutations in K-ras gene (17%) and 3 in p53
      gene (13%) which change the amino acid sequence of the protein p53. This is
      significantly lower than in sporadic cancer. Our data suggest that colon cancer
      in HNPCC might partly involve a distinct pathogenetic mechanism that involves
      other genes than those altered in sporadic tumors.

PMID- 9036877
TI  - Conserved region mutations of the p53 gene are concentrated in distal colorectal
      cancers.
AB  - Distal colorectal cancers, especially those in the rectum, are more aggressive
      and more commonly recurrent than proximal cancers. We studied the possible
      relationship between p53-gene mutation type and location of the tumour, since
      mutations in the conserved areas of the p53 gene have been suggested to result in
      a poorer outcome of colorectal cancer than mutations outside these areas. Exons 5
      to 8 of the p53 gene were studied in specimens from 72 colorectal-cancer
      patients. Polymerase-chain-reaction-amplified products of tumour DNA were
      analyzed by automated direct sequencing. Of the mutations detected in distal
      cancers, 71% were located in conserved regions of the gene, while only 42% of the
      mutations in proximal cancers were in these areas. In rectal cancers, 81% of the
      mutations were located in conserved regions. The tumours with mutations in the
      conserved regions were more often poorly differentiated (23%) than those with
      other mutations (0%). Our results indicate that mutations in the conserved
      regions of the p53 gene accumulate in distal but not in proximal tumours. This
      difference may be related to the more aggressive behaviour and to different
      aetiological factors associated with distal tumours.

PMID- 9036878
TI  - NM23 gene expression in human breast carcinomas: loss of correlation with cell
      proliferation in the advanced phase of tumor progression.
AB  - NM23 is a protein associated with tumor progression, expressed in all tissues and
      in human tumors. Reduced expression of NM23.H1 is related to high incidence of
      lymph node and distant metastasis or to poor prognosis of the patient in several
      human malignant tumors. In this study we analyze NM23 expression in non
      neoplastic mammary tissues surrounding the tumoral lesions, in human mammary
      carcinomas and in lymph node metastasis. Our analysis shows that NM23.H1
      expression is lower in the mammary cells surrounding the tumor than in the tumor
      itself. In the primary tumors we observed a negative trend between degree of
      local invasion and level of NM23.H1 expression. A further decrease of NM23.H1 was
      detected in the invasive tumors that metastasized to axillary lymph nodes and in
      the metastasis. NM23.H2 was always more highly expressed than NM23.H1, and
      reduced expression of NM23.H1 but not NM23.H2 was concordant with the presence of
      lymph node metastasis or local invasiveness of the primary tumor. A positive
      correlation between NM23.H1 mRNA content and cell growth rate of breast tumor
      cells has been confirmed. However, this trend was not maintained in cancer cells
      from tumors that metastasized to axillary lymph nodes and in metastatic cells; in
      these 2 situations the NM23.H1 mRNA content varied without any relationship to
      the proliferative rate of the cells. In addition, in comparison with the initial
      tumor, the metastatic cell population showed a strong decrease of NM23.H1
      expression and increased proliferative activity.

PMID- 9036879
TI  - Immunohistochemical study of MUC5AC expression in human gastric carcinomas using
      a novel monoclonal antibody.
AB  - In order to investigate the expression of MUC5AC mucin in normal gastric mucosa
      and gastric carcinomas, we produced 3 monoclonal antibodies (MAbs) using a MUC5AC
      synthetic peptide. The immunohistochemical study was performed using one of these
      MAbs (CLH2) which reacted with the different designs of peptides based on the
      MUC5AC tandem repeat and with native and deglycosylated mucin extracted from
      gastric tissues. CLH2 immunoreactivity was restricted to foveolar and mucopeptic
      neck cells in normal gastric mucosa. No reactivity was observed in type-I
      intestinal metaplasia. Out of 66 gastric carcinomas, 42 (63.6%) expressed MUC5AC.
      Most diffuse carcinomas were positive (83.3%), whereas only 59.3% of intestinal
      and 40.0% of atypical carcinomas expressed MUC5AC (p < 0.05). Gastric carcinomas
      with mixed pattern showed immunoreactivity in diffuse areas and decreased
      immunoreactivity in intestinal areas. Every early gastric carcinoma expressed
      MUC5AC, in contrast to 58.6% of advanced carcinomas (p < 0.05). A trend toward
      decreased immunoreactivity was observed in deep areas of advanced carcinomas in
      comparison with the respective superficial areas. Taking together the specific
      staining of foveolar and mucopeptic neck cells and the absence of
      immunoreactivity in intestinal metaplasia, we conclude that MUC5AC expression may
      be used as a marker of gastric differentiation. This assumption is further
      supported by the finding of MUC5AC immunoreactivity in most diffuse carcinomas,
      which usually display morphologic and histochemical signs of gastric
      differentiation. The expression of MUC5AC in early gastric carcinomas, regardless
      of their histologic type, suggests that all gastric carcinomas retain at least
      some cells with a gastric phenotype during the first steps of neoplastic
      development.

PMID- 9036880
TI  - Cell proliferation in 3,800 node-negative breast cancers: consistency over time
      of biological and clinical information provided by 3H-thymidine labelling index.
AB  - For breast cancer, many prognostic markers that initially appeared promising have
      failed to maintain their clinical predictive value. Few reports have analyzed the
      consistency over time of biological and clinical information provided by
      biomarkers. Tumour cell proliferation has acquired relevance as an indicator of
      prognosis and of response to treatment. Since its clinical role has been
      investigated for some decades, cell proliferation represents an ideal marker for
      an over-time validation. In 3,800 node-negative breast cancers recruited between
      1972 and 1991, the consistency of information provided by the 3H-thymidine
      labelling index (TLI), in terms of basic relations with other clinico
      pathological and biological variables and clinical predictivity, was evaluated
      using a combined analysis of results previously published by our group for
      distinct series of patients. Clinical predictivity was analyzed on a subset of
      2,067 patients given local-regional therapy until relapse and followed for a
      median time from 6 to 10 years. Over the entire period TLI maintained a weak
      direct relation with tumour size and an inverse strong relation with steroid
      receptors. An increase in TLI was observed for tumours in post-menopausal
      patients up to the mid 1980s. During 3 different accrual periods (1972-1983; 1984
      1987; 1988-1991), TLI was a consistent and independent predictor of relapse-free
      time, distant metastasis and overall survival, regardless of its consideration as
      a continuous variable or with a cutoff value of 3%. The reproducibility of our
      results over time provides support to the consistency of the methodology used and
      of the biological and clinical information obtained when using TLI as an
      indicator of breast cancer cell proliferation.

PMID- 9036881
TI  - Differential expression of multidrug resistance gene product, P-glycoprotein, in
      normal, dysplastic and malignant oral mucosa in India.
AB  - Multidrug resistance (MDR) in human cancer is often associated with over
      expression of the mdr-1 gene, which encodes a 170-kDa transmembrane protein,
      termed P-glycoprotein (P-gp). We evaluated the immunoreactivity of P-gp in oral
      tissues at different stages of tumorigenesis in the Indian population by flow
      cytometry, using the MRK-16 monoclonal antibody, which recognizes an external
      epitope of P-gp. The expression of P-gp was studied in human oral normal tissues
      (12 cases), dysplastic lesions (13 cases), primary untreated squamous-cell
      carcinomas (12 cases) and recurrent tumors (18 cases). Quantitative flow
      cytometric analysis of P-gp expression showed a significant increase in P-gp
      levels in untreated primary oral tumors (p < 0.01) and in dysplastic lesions (p <
      0.05) as compared with normal oral tissues. A marked significant increase in P-gp
      expression was observed in recurrent oral carcinomas as compared with normal oral
      tissues (p < 0.001) and dysplastic lesions (p < 0.01). Among recurrent tumors, a
      significant increase in the level of P-gp was observed in T4-stage tumors as
      compared with T3-stage tumors (p < 0.01). We conclude that P-gp is differentially
      expressed during oral tumorigenesis, and may be an indicator of the biological
      behavior of oral malignancies.

PMID- 9036882
TI  - Low frequency of hMSH2 mutations in Swedish HNPCC families.

PMID- 9036883
TI  - Angiogenesis does not predict clinical response to doxorubicin monotherapy in
      patients with locally advanced breast cancer.

PMID- 9036884
TI  - A randomized prospective trial of hyperbaric oxygen in a referral burn center
      population.
AB  - Various studies of the effect of hyperbaric oxygen (HBO) in a wide variety of
      disease entities have been carried out. In the treatment of burns, animal and
      human studies have yielded somewhat contradictory results. Controlled studies in
      humans are limited. A randomized study on the effect of HBO was conducted
      involving 125 burn patients admitted within 24 hours of injury who were matched
      by age, burn size, and presence or absence of inhalation injury. Patients in the
      treatment arm received oxygen at two atmospheres of pressure for 90 minutes twice
      a day for a minimum of 10 treatments and a maximum of one treatment per total
      body surface per cent burn. The control group was treated in a similar fashion,
      except for the absence of HBO. There were no statistically significant
      differences between the two groups for the outcome measures of mortality, number
      of operations, and length of stay for the survivors. In this large clinical
      trial, we were unable to demonstrate any significant benefit to burn patients
      from the use of HBO.

PMID- 9036885
TI  - Thoracotomy versus video-assisted thoracoscopic pleurectomy for spontaneous
      pneumothorax.
AB  - We reviewed our experience with thoracotomy (TH) and video-assisted thoracoscopic
      pleurectomy (VAT) for the treatment of recurrent spontaneous pneumothorax. Nine
      patients underwent 10 VATs. One patient had bilateral procedures 1 week apart.
      Nine patients underwent 10 THs. One patient had bilateral TH at the same session.
      The mean duration of postoperative hospital stay for VAT and TH was 5.7 days and
      6.4, respectively. VAT operative time was longer (128 vs 93.6 min in the TH
      group); however, the estimated blood loss was larger in the TH group (136 vs
      108.3 ml in the VAT group). There were no deaths in either group. In the VAT
      group, one patient had recurrence of pneumothorax 1 month after surgery. In the
      TH group, there was no recurrence of pneumothorax, but one patient had chronic
      pain at the site of the thoracotomy incision. One patient was lost to follow-up
      in each group. We conclude that VAT is a safe and reasonably effective treatment
      of spontaneous pneumothorax. However, large series with long-term follow-up are
      needed to place this procedure in its proper perspective.

PMID- 9036886
TI  - Relevance of quality improvement methods to surgical practice: prospective
      assessment of carotid endarterectomy.
AB  - Continuous quality improvement methods are increasingly being applied to health
      care systems, yet demonstration of outcome and cost benefits for surgical
      patients remains sparse. We used continuous quality improvement principles to
      specifically identify potential opportunities to reduce patient charges for
      carotid endarterectomy in our academic vascular surgery practice without
      compromising results. The targeted opportunities included: 1) limitation of
      laboratory examination, 2) selective cardiac stress testing, 3) discharge on 1st
      postoperative day, and 4) substitution of outpatient carotid duplex imaging for
      inpatient angiography. After 1 year, reductions in the average patient charge
      ($7700 versus $13,900, P < 0.001) and increases in payment/charge ratio (1.2
      versus 0.8; P < 0.001) were observed. These changes were primarily due to a
      reduction in length of stay (2.2 versus 5.7 days; P < 0.001). No significant
      difference in patient morbidity occurred. Reductions in charges occurred within
      the targeted areas of laboratory (-77%), cardiac testing (-73%), hospital room (
      60%), and radiology (-81%) utilization. Attention to the four factors identified
      by continuous quality improvement methods significantly reduced total patient
      charges without detrimental effects on patient outcome.

PMID- 9036887
TI  - Laparoscopic management of achalasia.
AB  - Eight patients with achalasia were treated using laparoscopic esophagomyotomy and
      anterior (Dor) fundoplication. The procedures were done on patients with
      clinical, radiological, and manometric diagnoses of achalasia. All procedures
      were completed laparoscopically. Seven (88%) of the patients were eating by the
      3rd postoperative day. The average hospital stay was 4.1 days (2-11 days);
      analgesic use was minimal. All myotomies were complete, with no patient requiring
      reoperation or dilation. The only complication was a mucosal laceration in one
      patient; this was successfully repaired laparoscopically. Follow-up from 8 to 20
      months shows that swallowing is excellent in 88 per cent and good in 12 per cent
      of patients, and no patient requires antireflux medication. These results support
      minimally invasive surgical myotomy as the treatment of choice for symptomatic
      achalasia.

PMID- 9036888
TI  - Upper-extremity arterial injury.
AB  - Current experience in the management of upper-extremity arterial injury in a
      Level I trauma center between 1992 and 1994 is reported. Arterial trauma was seen
      in 21 of 643 (3.3%) patients admitted with upper-extremity injury. The mechanism
      of injury was penetrating in 15 of 21 and blunt in 6 cases. Patient
      characteristics were: 18 of 21 male, mean age 28, left upper extremity 12 of 21,
      and 4 patients in shock. Preoperative angiography was performed in 12 of 21 cases
      (5 of 6 blunt and 7 of 15 penetrating). Involved arteries included: brachial
      (10), axillary (5), radial (3), and subclavian (3). Associated injuries were
      common: nerve (9), bone (7), and vein (5). Twenty patients were explored; 18 of
      20 underwent arterial repair (16 graft, 2 primary repair), and two proximal
      arteries were ligated. One intimal flap in the subclavian artery was observed,
      with a good result. Nerves were repaired in four cases, all with transection, and
      in four cases there was neurologic deficit without focal transection and no
      repair was performed. One patient died before his nerve injury could be repaired.
      Most venous injuries (four of five) were ligated, and three patients with blunt
      arterial injury underwent forearm fasciotomy. Immediate limb salvage was 100 per
      cent; there was one in-hospital mortality (4.7%) from exsanguination, and there
      was one persistent clinically significant late motor nerve deficit. Mean follow
      up was 94 days (range, 0-305 days). Upper-extremity arterial injury often can be
      managed without angiography, particularly in cases of penetrating trauma. Good
      results can be anticipated with prompt arterial and nerve repair combined with
      selective use of venous reconstruction and fasciotomy.

PMID- 9036889
TI  - Blunt popliteal artery trauma: a challenging injury.
AB  - Blunt popliteal artery trauma is a challenging injury, particularly when
      associated with major soft tissue damage. We reviewed our experience with this
      injury to determine 1) the incidence of vascular injury associated with fractures
      and/or dislocations about the knee, 2) the incidence of limb loss, and 3) factors
      associated with amputation. We treated 37 patients with 38 blunt popliteal artery
      injuries and either fractures about the knee or posterior knee dislocations.
      Patients who underwent primary amputations were excluded. The incidence of
      popliteal artery injuries with fractures about the knee was 3 per cent, whereas
      16 per cent of patients with posterior knee dislocations had vascular injuries (P
      < 0.05). Amputations were required in 14 of the 38 injured limbs (36%). None of
      these patients had a pulse or Doppler signal on admission, and 13 had major soft
      tissue injury. No patient with a pulse or Doppler signal lost a limb (P < 0.05).
      Limb loss was primarily related to limited venous outflow and/or severe infection
      in damaged tissue. Failure of the arterial repair rarely led to amputation,
      particularly in recent years. Two patients with angiographically proven arterial
      injuries were treated nonoperatively without complications. The incidence of
      vascular injuries associated with fractures about the knee is low, but somewhat
      higher with posterior knee dislocations. The overall 9 per cent rate of positive
      angiograms suggests that a selective approach may be indicated. The amputation
      rate remains high, but it has improved with an integrated, multidisciplinary team
      approach. In patients without a pulse or Doppler signal and with severe soft
      tissue injuries, primary amputation may be appropriate.

PMID- 9036890
TI  - Coagulopathy in severe closed head injury: is empiric therapy warranted?
AB  - Closed head injuries account for a significant portion of the morbidity and
      mortality following blunt trauma. Severe closed head injuries can be complicated
      by the development of a coagulopathy that may worsen blood loss and delay
      invasive neurosurgical procedures. Awaiting the results of coagulation studies
      prior to initiating treatment of such a coagulopathy introduces an inherent delay
      that may allow worsening of the coagulation disturbance and negatively influence
      outcome. This study was undertaken to see if a subgroup of patients with severe
      closed head injuries had a high probability of developing a coagulopathy and
      would warrant empiric treatment with fresh frozen plasma. The records of adult
      patients admitted to our trauma center with a Glasgow coma score (GCS) of < or =
      8 and an extracranial abbreviated injury score of < or = 2 during a 9-month
      period were reviewed. Patients with penetrating trauma or whose altered level of
      consciousness was due to sedation or shock were excluded. The presence of
      coagulation abnormalities was determined according to prothrombin time and
      partial thromboplastin time obtained on admission. The time to invasive
      neurosurgical procedures for both coagulopathic and noncoagulopathic patients was
      determined as well as the mean number of hospital days, intensive care unit days,
      and the mortality for each group. Eighty-one per cent of the patients with a GCS
      < or = 6 were coagulopathic on admission, and all patients with a GCS of 3 or 4
      were coagulopathic. In contrast, no patient with a score of 7 or 8 was
      coagulopathic. The coagulopathic patients tended to have a higher mortality than
      the noncoagulopathic patients (53 versus 22%) as well as longer intensive care
      unit and hospital stays. The mean time to neurosurgical intervention for the
      coagulopathic group was 226.0 +/- 190.9 minutes versus 84.8 +/- 38.4 minutes for
      the noncoagulopathic patients. We conclude that patients with closed head
      injuries who present with a GCS of 6 or less are candidates for empiric treatment
      for coagulopathy. Such treatment will negate the delay of awaiting coagulation
      studies. Whether or not such therapy shortens the interval between admission and
      neurosurgical procedures or alters outcome will require prospective study.

PMID- 9036891
TI  - Early intervention and aggressive management of infected median sternotomy
      incision: a review of 2242 open-heart procedures.
AB  - Infected median sternotomy following open-heart surgery is a devastating
      complication with an incidence of 0.4 to 5 per cent and mortality as high as 80
      per cent. Management varies from irrigation, debridement, closure with muscle,
      and skin flaps. We present our experience of early intervention and aggressive
      single-stage operative management. A retrospective chart review of all open-heart
      surgery patients was conducted from September 1984 through September 1994. Of the
      2242 patients, 52 had infected median sternotomy incisions (2.3% incidence). The
      mean length of stay for reconstructive procedures was 18 days. The median
      interval to detection was 15 days, whereas the median interval to intervention
      was 4 days. There were five (6.8%) failed procedures and nine (12.3%) staged
      procedures. There were six deaths (11.5% incidence), one prior to receiving
      operative intervention. There was one false aneurysm. Single-stage reconstruction
      is safe, with results better than multistage procedures. It may be safely
      performed with a high success rate (93%). Early recognition and intervention
      significantly decreases length of stay.

PMID- 9036893
TI  - Hemangiopericytoma: an unusual cause of upper gastrointestinal hemorrhage.
AB  - Hemangiopericytomas, first described in 1942, are rare, highly vascular neoplasms
      that arise from capillary pericytes. They are seen most commonly as a painless
      mass arising from the lower extremity but can also originate in the pelvic
      retroperitoneum and on the head, neck, chest, and abdomen. An unusual case is
      reported here of a patient presenting with recurrent massive upper
      gastrointestinal (GI) bleeding in whom a large hemangiopericytoma was found
      arising in the perisplenic soft tissues. Precedence exists in the literature for
      the association of hemangiopericytoma with GI bleeding. In prior reports,
      however, a mural origin of the tumor and subsequent bleeding into the GI lumen
      was demonstrated. In the case presented here, marked dilatation of the gastric
      and splenic vessels was noted, but there was no direct pathologic involvement of
      the stomach wall. It is proposed that superficial gastric erosions combined with
      the tumor-associated increased vascularity within the stomach wall led to
      recurrent major bleeding. Diagnosis of these tumors roentgenographically is
      nonspecific, but angiography is helpful. Morphological characteristics allow
      accurate histopathological diagnosis and provide prognostic information. The
      treatment of choice remains wide surgical excision, with the addition of
      radiation or chemotherapy in selected cases.

PMID- 9036892
TI  - The potential role of fecal carbonic anhydrase II in screening for colorectal
      cancer.
AB  - Several studies have demonstrated a relationship between mucosal carbonic
      anhydrase (CA) isoenzymes, particularly CA II, and cancer of the large intestine.
      Recent work has suggested the potential usefulness of fecal CA assay for
      colorectal cancer screening. This clinical study examined the accuracy of fecal
      CA II as a marker of adenocarcinoma of the colon and rectum. An enzyme-linked
      immunosorbent assay was used to measure CA II in urine, serum, and stool samples
      from 31 colorectal cancer patients and 26 control subjects. An immunochemical
      fecal occult blood test was also performed in all study participants. Urine and
      serum CA II were similar in the two study groups. However, both the prevalence
      and the mean level of fecal CA II in the cancer patients were significantly
      higher than those in the control group. The detection rate for CA II in the stool
      was 65 per cent for the cancer patients versus 4 per cent for the control
      population. The fecal CA II test was similar in sensitivity and specificity to
      the immunochemical fecal occult blood test (65 vs 48%; 96 vs 100%). Measurement
      of fecal CA II might be useful in screening for colorectal cancer.

PMID- 9036894
TI  - An unusual mechanism of burn injury due to flaming drinks.
AB  - Bars and cocktail lounges serve various forms of flaming drinks, usually made
      with very high-proof alcohol. The drinks are lit and then served. If additional
      alcohol from the bottle is added to a still-burning drink, flames may spread up
      the stream of alcohol into the bottle and cause a flash of flame out the bottle's
      neck. Injuries can require grafting. Three cases are reported. A 32-year-old
      white female sustained burns covering 10 per cent of her body surface, including
      the face. Surgery with split-thickness grafts were required. Pressure garments
      were prescribed for 6 months. A 34-year-old black female was burned by a
      "volcano" drink. Burns covered 20 per cent of her body surface, including the
      face. Split-thickness grafts were required on multiple occasions. Infected wounds
      healed slowly. Reconstructive surgery has so far required eight procedures. A 39
      year-old white male sustained severe burns to 10 per cent of his body, including
      the face. Grafting was carried out. Pressure garments were required. Permanent
      visible facial scarring is present in all three cases. This type of accident is
      readily preventable.

PMID- 9036895
TI  - The structured clinical instruction module as a tool for improving students'
      understanding of breast cancer.
AB  - The Structured Clinical Instruction Module (SCIM) is a novel format for teaching
      clinical skills. A multidisciplinary SCIM was presented to 30 medical students to
      improve their understanding of breast cancer. The SCIM consisted of 12 10-minute
      stations, each covering a different aspect of the diagnosis and management of
      breast cancer (e.g., history, physical examination, treatment options,
      mammography, cytology, and pathology). The students rotated through the various
      stations in groups of three. Nine patients and 14 faculty members participated.
      At the end of the SCIM, students, faculty, and patients rated their level of
      agreement (on a five-point scale ranging from "Strongly Disagree" to "Strongly
      Agree") with statements on a multi-item evaluation questionnaire. All ratings
      were positive. The students agreed most that the small-group format was an
      effective instructional method (mean, 4.6). Both students and faculty agreed that
      the SCIM increased students' clinical skills (mean, 4.4 in both evaluations).
      Faculty expressed a willingness to participate in future such workshops (mean,
      4.6). Patients agreed most strongly that they enjoyed the SCIM (mean, 5.0) and
      that faculty feedback to students was excellent (mean, 5.0). The SCIM was well
      received by all participants in this pilot project.

PMID- 9036896
TI  - Marsupialization of the pancreas for infected pancreatic necrosis.
AB  - Infected pancreatic necrosis is a devastating and lethal complication of acute
      pancreatitis. Late death is usually a result of sepsis. W.A. Altemeier and J.W.
      Alexander established in 1963 that open drainage of the necrotic pancreas is
      mandatory for survival (Arch Surg 1963;87:96-105). In 1981, E.D. Davidson and
      E.L. Bradley III concluded that "marsupialization" is the most effective method
      of open drainage (Surgery 1981;89:252-6). At our institution, we have a series of
      10 patients who have undergone marsupialization for treatment of infected
      pancreatic necrosis. Our mortality rate was 30 per cent. One death resulted from
      sepsis after an infected necrotic pancreas was found with a colonic anastomotic
      leak at emergency exploratory celiotomy. Of note, further debridement was not
      performed. A second death occurred in a female with idiopathic pancreatitis and
      leukocytopenia, and we are uncertain whether that played a role in the failure of
      surgical intervention. The third death was in a young alcoholic with
      hyperlipidemia and severe pancreatitis who was septic 8 days before surgery. The
      patient died on postoperative day 1. Of the survivors, some were old, many were
      septic, and all but one returned for further debridement. Our series supports
      open debridement of infected pancreatic necrosis as a life-saving maneuver and
      marsupialization as an effective means of open drainage.

PMID- 9036897
TI  - The effects of different corticosteroids on the healing colon anastomosis and
      cecum in a rat model.
AB  - Corticosteroids are known to adversely affect wound healing in experimental skin
      models; however, their effect on healing colonic anastomoses is still disputed.
      Different steroids have not been compared to each other in the same study. We
      studied the effect of equipotent doses of dexamethasone, hydrocortisone, and
      methylprednisolone on healing colon anastomoses in a rat model. High-dose steroid
      therapy was started 2 days prior to the operation and continued until the
      bursting pressures were measured at 5 and 7 days after the surgery. Anastomotic
      bursting pressure was not decreased for any of the steroid treatments when
      compared to the control, but the frequency of anastomotic rupture in the
      dexamethasone group at day 5 was significantly higher than either of the other
      steroid groups or the control group (P < 0.01). Bursting pressures of the intact
      cecum were lower in all the steroid-treated groups compared with the control
      group. We concluded that dexamethasone slows the rate of wound healing, but short
      term high-dose steroid therapy does not decrease the strength of the anastomoses
      as measured by bursting pressure.

PMID- 9036899
TI  - Prediction of trauma mortality using a neural network.
AB  - A neural network is a computerized construct consisting of input neurons (which
      process input data) connected to hidden neurons (to mathematically manipulate
      values they receive from all the input neurons) connected to output neurons (to
      output a prediction). Neural networks are created and trained via multiple
      iterations over data with known results. In 1993, 897 trauma patients were either
      declared dead in the emergency room (ER; 76 cases), admitted to the intensive
      care unit (427 cases, 36 deaths), or taken directly to the operating room (394
      cases, 29 deaths). Using only data available from the ER, a neural network was
      created, and 628 cases were randomly selected for training. After 268 iterations,
      the network was trained to correctly predict death or survival in all 628 cases.
      This trained network was then tested on the other 269 cases without our providing
      the death or survival result. Its overall accuracy was 91 per cent (244 of 269
      cases). It was able to predict correctly 60 per cent (12 of 20 cases) of the
      postoperative or post-intensive care unit admission deaths and 90 per cent (26 of
      29 cases) of the deaths in the ER. Computerized neural networks can accurately
      predict a trauma patient's fate based on inital ER presentation. The theory and
      use of neural networks in predicting clinical outcome will be presented.

PMID- 9036898
TI  - Limb ischemia: surgical therapy in acute arterial occlusion.
AB  - Mortality and amputation rates from acute arterial occlusion are reported from 7
      to 37 per cent and 10 to 30 per cent, respectively. Recent data from thrombolysis
      or peripheral arterial surgery suggest no significant differences between initial
      management with surgical or thrombolytic therapy. Mortality and amputation rates
      were in the above ranges. The last 230 procedures (216 patients) over 10 years
      were reviewed. All graft occlusions, cardiac catheterization injuries, and aortic
      balloon-related thromboses were excluded. Immediate and delayed amputation rates
      were 6.5 and 0.9 per cent. Death occurred in 21 patients (9.7%), with only 6
      deaths over the last 6 years (3.8%). Except for transesophageal echocardiography,
      perioperative studies were of limited value. Long-term anticoagulation was also
      not effective in preventing recurrent episodes. A mortality rate of 9.7 per cent
      and amputation rate of 7.4 per cent justifies an early aggressive surgical
      approach. Limited perioperative studies and less prolonged anticoagulation may
      also improve cost containment.

PMID- 9036900
TI  - Blunt pancreatic trauma: experience at a rural referral center.
AB  - The objective of this study was to compare mechanism of injury, treatment
      methods, and outcome of blunt pancreas trauma patients transferred from another
      hospital to those of patients brought directly from the scene. A retrospective
      review was conducted of 6078 patients treated at a Level I trauma center from
      1/1/90 to 12/31/94. Blunt pancreas injury was found in 39 (0.64%) patients (mean
      age, 33.2 years). Mechanism of injury included 34 (87%) motor vehicle crashes, 3
      (8%) motorcycle crashes, and 2 (5%) other injuries. There were 11 transfer
      patients (28%), and 28 (72%) admitted directly from the scene. Eighty-two per
      cent of the motor vehicle crash patients were unrestrained, and 35 per cent had
      ethanol intoxication. Exploratory laparotomy was performed on 32 (82%); eight
      (25%) required repair or resection; 22 (69%) had trivial injuries, at most
      requiring drainage; and two (6.3%) exsanguinated. No patients required Whipple
      resection or pancreatiocojejunostomy. At operation, an average of 2.5 associated
      intra-abdominal injuries were found. Overall survival was 35 of 39 (90%). Among
      the patients brought directly to the trauma center, 93 per cent survived, whereas
      survival among transferred patients was 82 per cent (chi2 = 0.19; P = 0.66).
      Blunt pancreatic injuries vary in severity, but radical resection is rarely
      required. Lack of safety restraint and ethanol use are major risk factors.
      Despite the high likelihood of associated injuries, survivability is high. No
      difference in outcome was seen between directly admitted and transferred
      patients.

PMID- 9036901
TI  - Mesenteric and omental cysts in children.
AB  - Mesenteric and omental cysts are rare intra-abdominal lesions. The rarity of
      these lesions, with an incidence of only about 1 in 140,000 hospital admissions,
      and the absence of characteristic clinical findings makes diagnosis difficult.
      Fourteen patients were treated for either mesenteric and/or omental cysts between
      1965 and 1994 at Egleston Children's Hospital at Emory University. Of the 14
      patients, 6 were female, 8 male; 3 were non-Caucasian, and 11 were Caucasian.
      They ranged in age from in-utero to 12 years old, with the most common presenting
      symptoms being abdominal distention (71%), pain (50%), vomiting (50%), and pain
      and distention (43%). Ultrasonography was the diagnostic method of choice. Other
      diagnostic modalities included intravenous pyelogram, barium enema, upper
      gastrointestinal series, CT scan, and MRI in selected patients. A single
      mesenteric cyst (79%) was most common, with only one patient (7%) having multiple
      mesenteric cysts as well as an omental cyst. The remaining two patients (14%) had
      single omental cysts. On gross examination, most (64%) were single, multilocular
      cysts. On pathological examination, the cysts ranged in size from 3.5 x 1 x 0.2
      cm to 30 x 40 x 10 cm, with a mean of 14.9 x 11.5 x 4.7 cm. Six of the 14
      contained fluid consistent with hemorrhage into the cysts. The most common
      treatment was simple excision (71%) followed by excision with partial bowel
      resection (29%). None received drainage alone as a treatment. There were no major
      postoperative complications and no reported recurrences of the cysts.

PMID- 9036902
TI  - Measurement of thromboxane and prostacyclin in valvulotomized human saphenous
      veins.
AB  - The present study was done to determine the effect of the modified Hall
      valvulotome technique on endothelial injury by measuring TxB2 and 6-keto
      PGF1alpha, the stable metabolites of thromboxane and prostacyclin, respectively.
      It was hypothesized that increased levels of these cyclooxygenase products would
      be an excellent indicator of vascular endothelial injury in the presence of the
      modified Hall valvulotome. Eight segments of human distal saphenous veins were
      obtained, each measuring approximately 4 cm in length, with diameters of
      approximately 2 to 3 mm. From these original vein segments, two groups of smaller
      vein segments were examined, with each group consisting of eight segments, each
      segment measuring 2 cm in length. The first group of vein segments was designated
      as the control group, and the second group of vessels had a modified Hall
      valvulotome (2.5 mm size) inserted into each segment to simulate valvulotomy.
      After this procedure, all vein segments were analyzed for levels of thromboxane
      and prostacyclin by a standard radioimmunoassay procedure. Results from the
      present study indicate that the modified Hall valvulotome technique in human
      saphenous veins does not significantly increase the levels of the cyclooxygenase
      metabolites thromboxane and prostacyclin relative to control conditions. However,
      the ratio of TxB2 formation 6-keto PGF1alpha production was increased in the
      valvulotomized vessel segments, indicating possible platelet release of
      thromboxane. Therefore, even though there was increased thromboxane production
      relative to prostacyclin levels in the modified Hall valvulotome technique, it
      still appears that this type of valvulotomy is relatively noninsulting to the
      endothelial cell lining.

PMID- 9036903
TI  - Pediatric seat belt injuries.
AB  - Two cases are reported that reiterate the significance of pediatric seat belt
      usage. Detection of associated injuries is difficult and often delayed. The
      presence of intra-abdominal free fluid on CT without solid organ injury should
      indicate the need for surgical intervention. Diagnostic peritoneal lavage usage
      in pediatric seat belt trauma may need to be re-evaluated. These cases emphasize
      the above as well as important postinjury clinical changes necessary for earlier
      diagnosis. A newly designed youth seat belt is presented to help prevent these
      injuries.

PMID- 9036904
TI  - A study of the normal values and habituation phenomenon of sympathetic skin
      response.
AB  - Sympathetic skin response (SSR) has been developed recently as a method of
      capturing the autonomic nerve response as a parameter of the sweat gland
      function. In this study, our aim was to obtain the normal values with regard to
      both amplitude and latency of SSR from 50 healthy subjects and to find out the
      habituation mode, which is one of the most characteristic phenomena of SSR. The
      measurements were recorded from the hand and foot by rectangular waveform
      electric stimulation. The correlation coefficient regarding hand and foot leads,
      amplitude, and latency were studied at normal values. The result was that no
      significant difference could be observed between the left and right leads with
      regard to amplitude and latency recorded from the hand and foot leads. However,
      between hand and foot leads, a significant difference was observed for both
      latency and amplitude. As for the habituation, electric stimulations were also
      applied to 20 healthy subjects (age range, 21-62 yr) in the same manner as that
      used in taking the normal values. For the latency and amplitude of the response
      in association with the stimulation trials (Rn), the mean values of the hand as
      well as the foot were determined by averaging the values recorded from both hands
      and both feet of the 20 subjects. These values were designated as the latency and
      the amplitude of the hand and foot from R1 to R15. The changes observed in
      response to the transition in the number of stimulations were statistically
      evaluated as a gradual decrease in the amplitude. This phenomenon is thought to
      be a result of learning. On the basis of the 15 consecutive stimulations, a
      decrease in amplitude to the 7th and 8th stimulations and constancy in the
      results thereafter was observed, although minor differences in the results were
      apparent between the hand and foot leads.

PMID- 9036905
TI  - A brief outpatient functional assessment measure: validity using Rasch measures.
AB  - The Medical Rehabilitation Follow Along (MRFA(TM)) is a brief outpatient
      functional assessment measure that was developed using Rasch analysis. The MRFA
      currently has musculoskeletal, neurologic, multiple sclerosis, cardiac, and
      pulmonary forms. Using Rasch scoring and selected scales, the 31-item
      musculoskeletal form of the MRFA was compared with and contrasted to a measure of
      general health status, the Medical Outcomes Trust SF-36. Content, construct, and
      criterion validity were addressed using scale scores before and after outpatient
      rehabilitation, as well as therapist ratings of improvement. The results
      supported the validity of inferences made from the MRFA scales using Rasch
      measures for persons with musculoskeletal problems. Rasch and raw scoring
      provided similar results with respect to the validity of the MRFA scales.
      Implications for the use of Rasch and raw scoring approaches with the MRFA are
      discussed.

PMID- 9036906
TI  - Augmented sensory nerve action potentials during distant muscle contraction.
AB  - We previously reported that the median sensory nerve action potentials (SNAP)
      increased in amplitude during ipsilateral abductor pollicis brevis contraction.
      The objectives of the present project were to study the timing and origin of this
      phenomenon and to eliminate the possibility of local artifact. Ten normal
      subjects were recruited. The baseline was established using ten threshold
      stimuli, which were delivered to the median nerve at the wrist at 0.2 Hz. Using
      the same stimulus strength, the SNAP was recorded while the tibialis anterior was
      contracted at 25, 50, 75, and 100% of maximum force. Responses were signal
      averaged. Results showed an increase in ipsilateral SNAP amplitude between
      baseline and maximum contraction of 6 +/- 2 microV (standard error, P = 0.004)
      and contralateral amplitude of 8 +/- 2 microV (standard error, P = 0.01).
      Statistical analysis was performed with analysis of variance for repeated
      measures and paired t test. The effect peaked between 0 and 10 min after
      contraction and lasted from 1.5 to more than 20 min after muscle relaxation. In
      conclusion, SNAP appear to be enhanced during and after muscle contraction.
      Theories concerning underlying causes for this event are discussed.

PMID- 9036907
TI  - Clinical trial of a cervical traction modality with electromyographic
      biofeedback.
AB  - A new design of cervical traction modality with closed loop traction weight
      control based on electromyographic (EMG) biofeedback was developed. It consists
      of the development of a high signal-to-noise ratio EMG scanner, on-line self
      adjusted traction weight controller, computer interface hardware, and closed loop
      biofeedback control software. Six healthy, young adults received conventional
      cervical traction to establish basic information of cervical EMG activities.
      Twenty-four patients with cervical radiculopathy were randomly divided into two
      groups for clinical assessment by conventional and new EMG biofeedback traction
      modality. The average electromyographic activity in healthy subjects ranged from
      2.41 to 3.49 microV, whereas EMG activity in patients with neck pain ranged from
      4.75 to 6.97 microV. There was a significant decrease of EMG activity during the
      whole traction phase, especially at pull phase in healthy subjects, but it was
      not as significant in patients with cervical radiculopathy. There was no
      significant change of myoelectric activity in the paraspinal muscles at vertebral
      levels C1-2, C3-4, and C5-6. Comparison of the average EMG activity of the
      paraspinal C-5 muscle in different phases of cervical traction showed a more
      significant decrease of EMG activity during the pull phase of traction as well as
      after traction in the high muscle tension group (with EMG activity above 5
      microV), especially with the biofeedback traction modality. The raised traction
      force from start to optimum was shortened from 4 to 2 wk to achieve the same
      effective outcome by biofeedback as conventional traction modality.

PMID- 9036908
TI  - Employment profiles in neuromuscular diseases.
AB  - Consumer and rehabilitation provider factors that might limit employment
      opportunities for 154 individuals with six slowly progressive neuromuscular
      diseases (NMD) were investigated. The NMDs were spinal muscular atrophy (SMA),
      hereditary motor sensory neuropathy (HMSN), Becker's muscular dystrophy (BMD),
      facioscapulohumeral muscular dystrophy (FSHD), myotonic muscular dystrophy (MMD),
      and limb-girdle syndrome (LGS). Forty percent were employed in the competitive
      labor market at the time of the study, 50% had been employed in the past, and 10%
      had never been employed. The major consumer barrier to employment was education.
      Other important factors were type of occupation, intellectual capacity,
      psychosocial adjustment, and the belief by most individuals that their physical
      disability was the only or major barrier to obtaining a job. Psychological
      characteristics were associated with level of unemployment. However, physical
      impairment and disability were not associated with level of unemployment. There
      also were differences among the types of NMDs. Compared with the SMA, HMSN, BMD,
      and FSHD groups, the MMD and LGS groups had significantly higher levels of
      unemployment, lower educational levels, and fewer employed professional,
      management, and technical workers. Nonphysical impairment factors such as a low
      percentage of college graduates, impaired intellectual function in some
      individuals, and poor psychological adjustment were correlated with higher
      unemployment levels in the MMD group. Unemployment in the LGS group was
      correlated with a failure to complete high school. Major provider barriers to
      employment were the low level of referrals to Department of Rehabilitation by
      physicians and the low percentage of acceptance into the State Department of
      Rehabilitation. The low rate of acceptance was primarily attributable to the low
      number of referrals compounded by a lack of counselor experience with individuals
      with NMD. Both consumer and provider barriers may contribute to the lack of
      interest in obtaining a job.

PMID- 9036909
TI  - Physiotherapy and occupational therapy: a geriatric experience in the acute care
      hospital.
AB  - The continuously growing segment of the geriatric population with the high
      incidence and prevalence of comorbidity and disability suggests that enhanced
      preventive and rehabilitative programs will be mandatory. The early arrangement
      of comprehensive assessment and rehabilitation services is extremely important
      not only in preventing the decline of patients in the acute care settings and
      successive prolonged care before discharge, but also in improving functional
      status at discharge. We have considered the effectiveness of a rehabilitation
      program in acute medical care of the elderly. This article discusses a pilot
      project being carried out at Catholic University Hospital "A. Gemelli" of Rome.

PMID- 9036910
TI  - The painful hemiplegic shoulder: effects of intra-articular triamcinolone
      acetonide.
AB  - Effects of intra-articular triamcinolone acetonide on pain and passive range of
      motion (ROM) in the painful hemiplegic shoulder were studied. A Multiple baseline
      (or AB) design across seven subjects was used. The length of the baseline
      condition (or A phase) was either 2 or 3 wk, and randomized across subjects.
      Subsequently, a treatment condition (or B phase) of 4 wk was applied during which
      three intra-articular injections of triamcinolone acetonide were administered at
      day 1, 8, and 22. Pain and ROM were the primary outcome parameters and were
      measured three times each week by means of a visual analogue scale (VAS) and a
      fluid-filled goniometer, respectively. In addition, a number of secondary outcome
      parameters were assessed, i.e., spastic muscle activity (Ashworth scale), motor
      function (Fugl-Meyer index), upper limb function (action research arm test) and
      signs and symptoms of a shoulder hand syndrome (clinical scoring list).
      Statistical analysis of the combined time series showed significant effects on
      pain (P = 0.025). Analysis of the individual time series revealed that five out
      of seven patients had significant reduction of pain. ROM improved significantly
      in four out of seven patients. However, improvement of ROM did not reach
      significance at the group level (P = 0.13). None of the secondary parameters
      showed significant changes. The correlation coefficient between upper limb
      function (ARA) at intake and size of treatment effect approached a level of
      significance (P = 0.09). The results indicate that intra-articular triamcinolone
      may be of benefit in reducing hemiplegic shoulder pain.

PMID- 9036911
TI  - Predictive power of clinical symptoms in patients with presumptive deep venous
      thrombosis.
AB  - The predictive power of clinical symptoms in the diagnosis of deep venous
      thrombosis (DVT) was assessed using a retrospective design. The sample consisted
      of 61 rehabilitation patients who were referred for Doppler ultrasonography.
      Patients had a mean age of 60.6 (standard deviation, 18.4) years. Clinical
      measures documenting presence of swelling, warmth, fever, and lower limb
      asymmetry (> 2.5 cm) were correlated with the outcome of venous duplex Doppler
      examinations. Clinical symptoms had low sensitivity (0.07-0.33) but generally
      higher specificity (0.76-0.85) for DVT. Positive predictive power was lowest for
      fever (0.08) and highest for swelling (0.66). Prevalence rates for DVT were
      greatest (0.41) in patients presenting with multiple symptoms. Results suggest
      clinical predictors of DVT remain elusive. A high rate of false-positives based
      on clinical findings from examination is acceptable given the low risk associated
      with ultrasonography and the clear benefit of early diagnosis of DVT.

PMID- 9036912
TI  - Physical activity and four-year development of back strength in children.
AB  - Physical activity in children is important, both for its direct benefits and for
      establishing potentially lasting future behaviors. Understanding the development
      of back strength in children is also important, because decreased back strength
      is associated with low back pain in adults. We hypothesized the following: (1) a
      substantial percentage of children do not participate in adequate physical
      activity; (2) the development of back strength corresponds to the development of
      strength of appendicular muscles; (3) there is a positive relationship between
      physical activity and back strength. The study included 53 boys and 43 girls,
      aged 10 to 19 yr, who had undergone isometric strength testing 4 yr previously.
      From responses to a questionnaire, each child's level of physical and sedentary
      activity was calculated. Isometric back flexion and extension were measured with
      the same method used 4 yr previously. Statistical analyses were performed,
      including quadratic regressions to estimate the rate of increase in strength,
      height, and weight. The following results were found: (1) during the month before
      testing, 21 children participated in physical activity for less than 30 min/day;
      (2) the level of physical activity was significantly associated with back flexion
      and back extension (P = 0.03 for both); (3) the peak rate of increase in back
      strength occurred approximately 1 yr after the peak rate of increase in height.
      We conclude the following: (1) measures should be taken to increase the
      involvement of children in athletic activities; 2) physical activity may be
      important in the development of back strength; (3) the pattern of back strength
      development seems to be the same as that for development of muscles of the
      appendicular skeleton.

PMID- 9036913
TI  - Upper limb functional electrical stimulation for walker ambulation in hemiplegia:
      a case report.
AB  - Electrical stimulation has been sporadically used in the treatment of hemiplegia.
      Reported benefits include decreasing spasticity, providing a supplementary means
      for range of motion exercises, increasing strength, and improving local blood
      flow in a paretic or paralyzed limb. Some studies have also shown functional
      gains in the hemiplegic upper limb following treatment with electrical
      stimulation. Nevertheless, there have been very few reports of the use of
      neuromuscular stimulation to achieve new hemiplegic upper limb activity not
      possible without the electrical stimulation. This is a case report of a head
      injury patient who was able to begin ambulation with a walker, without physical
      assistance, for the first time in the 16 yr since his injury. A new electrical
      stimulation device (Handmaster) initially used therapeutically, and then
      functionally, provided a reliable, strong grasp and release and was instrumental
      in achieving the new level of function. The device proved to be easy to use in
      the home, giving the patient microprocessor-controlled therapeutic and patterned
      functional electrical stimulation.

PMID- 9036914
TI  - Ossification of the ligamentum flavum causing thoracic myelopathy: a case report.
AB  - Ossification of the ligamentum flavum is a well reported clinicopathologic entity
      causing narrowing of the spinal canal and subsequent spinal cord compression. The
      patient described in this case report complained of 9 mo of middle and lower back
      pain, difficulty with balance, progressive gait disturbance, and recent onset of
      bladder retention. Magnetic resonance imaging and computed tomographic scan
      revealed a bone density mass at the T2-3 level causing 25% cord compression and
      edema. A decompressive laminectomy was performed at T-2. The etiology of the
      compression was found to be attributable to an ossified ligamentum flavum at the
      T-2 level, which was confirmed by histologic examination. His neurologic signs
      and symptoms and functional status markedly improved after surgery and subsequent
      comprehensive rehabilitation. The patient was able to ambulate independently with
      a walker as opposed to previously being wheelchair-bound. Prompt surgical
      intervention and appropriate rehabilitation management play a key role in
      improving the functional outcome of myelopathy caused by ossified ligamentum
      flavum. This article acquaints rehabilitation personnel with the clinical
      features, proposed etiologies, association with other diseases, work-up,
      treatment, and rehabilitation concerns of patients with myelopathy caused by
      ossified ligamentum flavum.

PMID- 9036915
TI  - Failure of magnetic resonance imaging to reveal the cause of a progressive
      cervical myelopathy related to postoperative spinal deformity: a case report.
AB  - Imaging studies have achieved a high degree of diagnostic accuracy for many
      disorders of the spinal cord but have significant limitations. We report on the
      case of a 49-yr-old man who developed neck pain and arm numbness. He was found to
      have extensive cervical spondylosis, with spinal cord impingement at C3-4 and
      cervical radiculopathy. He underwent a C3-7 laminectomy, with transient
      improvement in his symptoms. During the ensuing year, he developed increased
      weakness of the upper limbs, evidence of cervical myelopathy, and a severely
      flexed posture of the cervical spine. Magnetic resonance imaging (MRI) revealed
      cervical spinal cord atrophy but no evidence of extrinsic spinal cord
      compression. Cervical flexion and extension films revealed reversal of the normal
      cervical lordosis without segmental instability. Despite the absence of
      confirmatory radiologic studies, the patient was felt to have clinical evidence
      of intermittent compression of his cervical spinal cord attributable to excessive
      cervical kyphosis, was provided with a cervical collar, and subsequently
      underwent surgical stabilization. His cervical myelopathy showed marked
      improvement with these treatments. We conclude that intermittent compression of
      the spinal cord, occurring in the erect position, was not apparent on the MRI
      films obtained in the supine position. Flexion and extension films, obtained in
      the upright position, documented his abnormal cervical anatomy but did not reveal
      substantial segmental instability. Spinal deformity without segmental instability
      may cause cervical myelopathy after multilevel cervical laminectomies without
      evidence of extrinsic compression on MRI.

PMID- 9036916
TI  - Uniform data system for medical rehabilitation: report of first admissions for
      1995.

PMID- 9036917
TI  - Special qualifications in spinal cord injury medicine: a commentary.

PMID- 9036918
TI  - Mutations in the COL3A1 gene result in the Ehlers-Danlos syndrome type IV and
      alterations in the size and distribution of the major collagen fibrils of the
      dermis.
AB  - Ehlers-Danlos syndrome type IV (EDS type IV) results from heterozygosity for
      mutations in the COL3A1 gene that encodes the chains of type III procollagen. By
      using light, transmission, and scanning electron microscopy, we examined skin
      biopsies from 22 individuals with EDS type IV in whom the COL3A1 mutations had
      been identified. The most striking changes in EDS type IV were correlated with
      point mutations that substituted a residue for a glycine near the carboxyl
      terminal end of the triple-helical domain of pro alpha1(III). In three cases with
      the mutation G1012R, G1018V, or G1021E, cells in the dermis had extremely dilated
      rough endoplasmic reticulum (RER), the dermis was thin, and there was a reduced
      proportion of collagen although the proportion of elastic fibers appeared
      increased. In these tissues, collagen fibrils were small (65-80 nm) compared to
      normal (95-110 nm). Fibrils 80-90 nm in diameter and moderately dilated RER were
      found with mutations G769R, G373R, and G061E and with exon-skipping mutations of
      exons 34 and 45. With mutations G034R and G016C and exon-skipping mutations that
      deleted the sequences of exons 7, 8, 14, 18, 24, and 27, fibrils were more
      variable in size (85-120 nm). The composite collagen fibrils characteristic of
      EDS types I and II were not found in EDS type IV. These findings indicate that
      mutations in the COL3A1 gene have effects on secretion, fibrillogenesis, and skin
      architecture that reflect the position and nature of the mutation.

PMID- 9036919
TI  - Platelets play a role in the pathogenesis of the irritant reaction in mice.
AB  - The irritant reaction is a model of local inflammation that results from the
      epicutaneous application of a small molecule with irritating properties such as
      trinitrochlorobenzene (TNCB). The irritant reaction is mediated by tumor necrosis
      factor (TNF) and is characterized by skin edema and neutrophil (PMN)
      infiltration. The aim of this study was to explore the role of platelets in the
      pathogenesis of the irritant reaction. Mice depleted of platelets by an anti
      platelet antibody showed a decrease in edema upon the application of a low dose
      of TNCB--chosen for causing an irritant reaction that is not complicated by
      intravascular fibrin deposition and hemorrhage--but no significant change in PMN
      infiltration. There was platelet trapping in TNCB-treated ears that was maximum
      between 2 and 6 h after TNCB application. Platelets lined the venular
      endothelium, which was intact in the absence of hemorrhage, and were not
      accompanied by fibrin. Mice treated with anti-TNF, anti-CD11a, anti-CD18, or anti
      CD54 antibodies showed a decrease in platelet trapping, edema, and PMN
      infiltration. Platelets contribute to the pathogenesis of the irritant reaction
      and are necessary for edema to develop but not for PMN infiltration. The role of
      platelets implicates their early localization in the dermal venules, which
      depends, at least in part, on TNF and on the adhesion molecules involved in the
      interaction between CD11a/CD18 and CD54.

PMID- 9036920
TI  - Induction of hapten-specific tolerance of human CD8+ urushiol (poison ivy)
      reactive T lymphocytes.
AB  - The interaction of CD28 with B7 molecules (CD80 or CD86) is an essential second
      signal for both the activation of CD4+ T cells through the T-cell receptor and
      the prevention of anergy. We studied the requirement of hapten-specific human
      CD8+ cells for CD28 co-stimulation in recognition of hapten, and anergy
      induction. Urushiol, the immunogenic hapten of poison ivy (Toxicodendron
      radicans), elicits a predominantly CD8+ T-cell response. Autologous PBMC were pre
      incubated with urushiol prior to fixation by paraformaldehyde. Fixed antigen
      presenting cells were unable to present urushiol to human CD8+ urushiol-specific
      T cells. Addition of anti-CD28, however, overcame this antigen-presenting defect,
      enabling CD8+ cells to proliferate. Fixation of antigen-presenting cells prevents
      upregulation of B7, and addition of anti-CD28 substitutes for this signal.
      Proliferation of CD8+ T cells in response to urushiol was blocked by CTLA4Ig, a
      recombinant fusion protein that blocks CD28/B7 interactions. Preincubation of
      urushiol-specific CD8+ cells with fixed PBMC + urushiol for 7 d induced anergy.
      Anergic CD8+ cells were viable and able to proliferate in response to IL-2, but
      not in response to urushiol. Induction of anergy required the presence of
      urushiol, and pre-incubation with irradiated PBMC + urushiol did not have this
      effect. It is proposed that anergy was induced by presentation of urushiol by
      fixed PBMC, in the absence of adequate co-stimulation signals. Induction of
      anergy by blocking of co-stimulation could potentially induce clinical
      hyposensitization to haptens.

PMID- 9036921
TI  - TGF-beta3 stimulates and regulates collagen synthesis through TGF-beta1-dependent
      and independent mechanisms.
AB  - In contrast to the TGF-beta1 and beta2 isoforms, TGF-beta3 has shown the ability
      to downregulate scarring and fibrosis in vivo under certain experimental
      conditions. In this study, we determined the direct effects of TGF-beta3 on
      cultures of human dermal fibroblasts. TGF-beta3 (0.1 to 100 pg per ml) increased
      DNA synthesis up to 50% (p < 0.01, r = 0.970), collagen protein synthesis up to
      200% (dose range of 0.1 to 5 ng per ml, p < 0.001, r = 0.990), and increased
      alpha1(I) procollagen mRNA levels (r = 0.999), with maximal effects (200% of
      control) observed by 24 h. Collagen lattice contraction was increased by more
      than 50% in response to TGF-beta3 (p < 0.001), and to a similar extent as the TGF
      beta1 isoform. Stimulation of collagen synthesis and of alpha1(I) procollagen
      mRNA levels in response to TGF-beta3 was partially blocked by a TGF-beta1
      specific anti-sense oligonucleotide but was still detectable (35% greater than
      baseline) when TGF-beta3 was added to dermal fibroblasts from TGF-beta1 knock-out
      mice. In contrast with these stimulatory effects, however, downregulation of
      alpha1(I) procollagen, alpha1(III) procollagen, and TGF-beta1 mRNA levels toward
      baseline occurred when TGF-beta3 (0.1 to 5 ng per ml) was added simultaneously
      and in combination with TGF-beta1. We conclude that stimulation of collagen
      synthesis by TGF-beta3 occurs through TGF-beta1-dependent and independent
      pathways. By downregulating the response to TGF-beta1 and by shifting from one
      pathway to the other, TGF-beta3 can dampen and provide fine-tuning to the overall
      TGF-beta's induced program of collagen deposition.

PMID- 9036922
TI  - Hypoxia regulates the expression of vascular permeability factor/vascular
      endothelial growth factor (VPF/VEGF) and its receptors in human skin.
AB  - Tissue hypoxia is a characteristic feature of malignant tumors and healing
      wounds, conditions that are associated with angiogenesis and with increased
      expression of vascular permeability factor (VPF; also called vascular endothelial
      growth factor, VEGF), a selective endothelial cell mitogen inducing microvascular
      hyperpermeability in vivo. We investigated the regulation of VPF/VEGF and its
      receptors by tissue hypoxia in normal human skin explants and in cultured skin
      cells in vitro. VPF/VEGF mRNA expression was dramatically upregulated in
      epidermal keratinocytes, dermal fibroblasts, and dermal microvessels after 24 h
      of skin organ culture. Hypoxia also enhanced the expression of VPF/VEGF in
      cultured epidermal keratinocytes and dermal microvascular endothelial cells
      (predominantly VPF/VEGF121 and VPF/VEGF165) and in dermal fibroblasts (additional
      upregulation of VPF/VEGF189). The expression of the VPF/VEGF receptor Flt-1 was
      selectively induced on dermal microvessels in skin explant cultures and in dermal
      endothelial cell monolayer cultures under hypoxic conditions. In contrast, the
      KDR receptor was downregulated by hypoxia. These results suggest that hypoxia
      likely regulates cutaneous angiogenesis and microvascular permeability by two
      distinct mechanisms: (i) Induction of VPF/VEGF in epithelial and mesenchymal
      cells, including endothelial cells. (ii) Differential modulation of VPF/VEGF
      receptor expression by microvascular endothelial cells. These mechanisms may be
      of importance in the pathogenesis of healing wounds and some malignant tumors
      that are commonly characterized by hypoxia and overexpression of VPF/VEGF.

PMID- 9036923
TI  - Scleroderma fibroblasts show increased responsiveness to endothelial cell-derived
      IL-1 and bFGF.
AB  - Fibroblasts cultured from lesional skin in scleroderma (systemic sclerosis)
      demonstrate an activated phenotype that may be important in pathogenesis.
      Endothelial cell-derived cytokines can modulate fibroblast properties, and
      endothelial cell changes occur early in scleroderma. Thus, endothelial cell and
      fibroblast dysfunction may be linked through the paracrine activity of soluble
      endothelial cell products. We have explored endothelial cell-fibroblast
      interactions in vitro by investigating the modulation of scleroderma and control
      fibroblast properties by endothelial cell-conditioned medium (EC-CM). EC-CM
      caused a concentration-dependent stimulation of fibroblast DNA and protein
      synthesis and upregulation of cell surface ICAM-1 expression. Scleroderma
      fibroblasts showed consistently greater responses than control cells. Medium
      conditioned by mechanically wounded endothelial cells had a greater effect than
      that from resting endothelial cells. Pre-incubation of EC-CM with anti-bFGF
      significantly reduced the promotion of fibroblast thymidine incorporation but did
      not affect endothelial cell-induced leucine incorporation. Conversely, anti-IL-1
      antibodies abrogated EC-CM-induced leucine incorporation and ICAM-1 expression
      but did not diminish thymidine incorporation. Recombinant bFGF or IL-1 modulated
      fibroblast properties similarly. These data demonstrate that endothelial cell
      derived IL-1 and bFGF modulate fibroblast properties independently and that
      lesional scleroderma strains are more responsive than control fibroblasts to
      endothelial cell-induced modulation, which supports the hypothesis that altered
      endothelial cell-fibroblast communication may be involved in the pathogenesis of
      scleroderma.

PMID- 9036924
TI  - Post-transcriptional regulation of neurofibromin level in cultured human
      melanocytes in response to growth factors.
AB  - Among the symptoms that characterize neurofibromatosis type 1 (NF1) are
      pigmentation anomalies such as cafe au lait spots. It has been suggested that the
      reduction of the neurofibromin level in the epidermis of NF1 patients is
      responsible for the observed signs such as altered melanogenesis and altered
      density of melanocytes. Our studies show that in cultured normal human
      melanocytes, the neurofibromin level can be varied in vitro over a wide range by
      using different culture conditions. The influence of factors that control
      differentiation and proliferation of melanocytes on neurofibromin levels was
      studied. Immunoprecipitation followed by western blotting showed a 3- to 4-fold
      increase of neurofibromin after stimulation by PMA or bFGF, respectively, and a
      1.5-fold increase in cells stimulated with steel factor. The increase of
      neurofibromin was not paralleled by a higher NF1 mRNA level as proved by northern
      blotting. Pulse-chase experiments with 35S-labeled melanocytes revealed an
      approximately 3-fold increase in the half-life of neurofibromin in bFGF- or PMA
      stimulated cells compared to controls. These results indicate that the
      neurofibromin level of cultured melanocytes can be regulated by a mechanism
      independent of NF1 gene transcription and translation, which might influence the
      degradation rate of the protein.

PMID- 9036925
TI  - Tissue inhibitor of metalloproteinase 1 (TIMP-1) may be an autocrine growth
      factor in scleroderma fibroblasts.
AB  - In scleroderma (systemic sclerosis, SSc), an autoimmune disorder in which
      excessive extracellular matrix is deposited in skin and internal organs, one of
      the suggested contributory factors to the development of fibrosis is a decrease
      in collagenase activity that may be related to levels of serum tissue inhibitors
      of metalloproteinases 1 (TIMP-1). We recently reported that the serum TIMP-1
      levels in SSc patients were elevated compared with normal controls. To determine
      the biologic significance of TIMP-1 in SSc, we compared the proliferative effects
      of TIMP-1 between normal and SSc fibroblasts. TIMP-1 showed significant mitogenic
      activity for both normal and SSc fibroblasts. The mitogenic responses to TIMP-1
      (33-100 ng/ml) in SSc fibroblasts, however, were significantly greater than those
      in normal controls and were completely neutralized in the presence of anti-TIMP-1
      IgG. Moreover, anti-TIMP-1 IgG partially but significantly blocked the basal
      mitogenic activities of SSc fibroblasts. SSc fibroblasts produced increased
      amounts of TIMP-1 relative to normal fibroblasts, as confirmed by western
      blotting, ELISA, and RT-PCR techniques. In contrast, transforming growth factor
      beta1 (TGF-beta1) upregulated TIMP-1 production in normal fibroblasts but not in
      SSc fibroblasts with elevated spontaneous secretion of TIMP-1. These observations
      suggest that TIMP-1 may play an important role as an autocrine growth factor in
      the fibrotic process in SSc.

PMID- 9036926
TI  - Dexamethasone abrogates the fibrogenic effect of transforming growth factor-beta
      in rat granuloma and granulation tissue fibroblasts.
AB  - Administration of TGF-beta, a fibrogenic inflammatory growth factor, promotes
      fibrosis and scarring. Dexamethasone, an anti-inflammatory steroid, inhibits
      wound healing and reduces fibrosis. The current studies were initiated to
      determine whether the co-administration of dexamethasone was able to abrogate the
      fibrogenic effect of TGF-beta. Polyvinyl alcohol sponges were implanted
      subcutaneously on the abdominal area of rats and directly injected with vehicle,
      dexamethasone, TGF-beta, or dexamethasone plus TGF-beta. Dexamethasone was able
      to block the fibrogenic effect of TGF-beta. Collagen and noncollagen protein
      synthesis was measured as a function of TGF-beta or dexamethasone concentrations
      in fibroblasts isolated from granulation tissue. Addition of dexamethasone to
      cultures treated simultaneously with TGF-beta blocked the fibrogenic response of
      TGF-beta. To study the molecular regulation of collagen gene expression by TGF
      beta or dexamethasone, fibroblasts derived from granulation tissue were stably
      transfected with the ColCat 3.6 plasmid, which contains the rat pro alpha1(I)
      collagen promoter linked to the chloramphenicol acetyltransferase (CAT) gene.
      Dexamethasone decreased CAT activity whereas TGF-beta increased the activity of
      this reporter gene. The increase in CAT activity observed with TGF-beta treatment
      was significantly decreased when dexamethasone was added to the cultures,
      although CAT activity did not return to control level. Since collagen synthesis
      in fibroblasts treated simultaneously with dexamethasone and TGF-beta1 was found
      to be the same as that of untreated samples, the data indicate that there is a
      dexamethasone-mediated posttranscriptional regulation of pro alpha1(I) collagen
      mRNA. These studies demonstrate that at the in vivo level, the cellular level,
      and the molecular level, dexamethasone is able to block the fibrogenic effect of
      TGF-beta.

PMID- 9036927
TI  - UVB irradiation alters cellular responses to cytokines: role in extracellular
      matrix gene expression.
AB  - Solar radiation causes cutaneous photodamage characterized by alterations in the
      quantity and structure of the extracellular matrix. We determined the direct and
      cytokine-mediated effects of UV irradiation on mRNA levels for two matrix
      elements, tropoelastin and fibrillin 1. (i) Comparison of normal versus end-stage
      photodamaged skin failed to reveal differences in these message levels. (ii)
      Acutely irradiated skin showed suppression of both tropoelastin and fibrillin
      mRNAs. (iii) UVB irradiation (50 mJ) of cultured skin fibroblasts suppressed
      fibrillin mRNA by 50%, consistent with a direct effect of radiation. Addition to
      the cultured fibroblasts of several cytokines upregulated by UVB showed that IL
      1alpha had no effect on fibrillin mRNA in unirradiated cells, but in irradiated
      cells, this cytokine enhanced the suppression of fibrillin mRNA. There were no
      changes in the message stability, suggesting altered gene transcription. In
      contrast, UVB had no effect on tropoelastin mRNA levels in cultured fibroblasts,
      indicating the absence of a direct effect of radiation. IL-1alpha stimulated
      tropoelastin mRNA 2.8-fold in unirradiated cells, and this stimulation was
      entirely blocked by UVB. Overall, our results indicate acute suppression of
      matrix genes by UVB in vivo. The suppression of fibrillin message was a direct
      effect of UVB on fibroblasts and was augmented by IL-1alpha. Suppression of
      tropoelastin message by UVB occurred in vitro only in IL-1alpha-stimulated cells.
      We conclude that UVB substantially alters the pattern of cellular response to
      cytokines. The interplay between UVB and cytokines is essential to explain the
      acute responses of matrix genes to UVB in vivo.

PMID- 9036928
TI  - Pervanadate mimics IFNgamma-mediated induction of ICAM-1 expression via
      activation of STAT proteins.
AB  - Differential expression of intercellular adhesion molecule-1 (ICAM-1) in the
      epidermis plays a critical role in the regulation of cutaneous inflammation,
      immunologic reactions, and tissue repair. Transcriptional upregulation of ICAM-1
      in response to interferon-gamma (IFNgamma) occurs through a palindromic response
      element pIgammaRE. pIgammaRE is homologous to IFNgamma-activated sequences, which
      bind to tyrosine phosphorylated members of the transcription factor family known
      as signal transducers and activators of transcription (STAT). The importance of
      tyrosine phosphorylation events in the STAT pathway led us to investigate the
      effect of the protein tyrosine phosphatase inhibitor, pervanadate, on ICAM-1
      expression. We show that treatment of A431 cells and human keratinocytes with
      pervanadate stimulates protein complex formation on pIgammaRE in a time- and
      concentration-dependent manner. As demonstrated by mobility supershift assays,
      the pervanadate-stimulated complex is similar to the IFNgamma-stimulated complex
      and contains Stat1. Pervanadate treatment also led to an increase in overall
      protein tyrosine phosphorylation and phosphorylation of Stat1, as well as the
      subsequent increase in ICAM-1 mRNA and cell surface protein levels. These data
      show that pervanadate can mimic each step in the IFNgamma-mediated pathway
      leading to ICAM-1 expression, demonstrate the ability of a pharmacologic agent to
      bypass the standard cytokine-receptor interaction required for increased ICAM-1
      expression, and emphasize the importance of protein tyrosine phosphatases and
      protein tyrosine kinases in mediating inflammatory responses in the skin.

PMID- 9036929
TI  - L-ascorbic acid inhibits UVA-induced lipid peroxidation and secretion of IL
      1alpha and IL-6 in cultured human keratinocytes in vitro.
AB  - We investigated the antioxidative effect of L-ascorbic acid on lipid peroxidation
      and on secretion and mRNA expression of IL-1alpha and IL-6 after UVA irradiation
      (20 J/cm2) in cultured human keratinocytes. Lipid peroxidation was measured by
      (i) high performance liquid chromatography with UV detection of malondialdehyde
      (MDA) at 256 nm and (ii) spectrometric measurement of thiobarbituric acid
      reactive substances (TBARS). To evaluate UV-induced cytotoxicity, we assessed
      cell membrane damage by measuring lactate dehydrogenase (LDH) release. UVA
      induced lipid peroxidation in cultured human keratinocytes was inhibited by
      ascorbic acid in a concentration-dependent manner: MDA protein equivalent was
      reduced by 47% (10(-6)), compared to keratinocytes not exposed to L-ascorbic acid
      (p < 0.05), and the TBARS showed a concentration-dependent decrease of 49% (10(
      6) M) in L-ascorbic acid-supplemented cultures compared to controls (p < 0.05).
      LDH release was decreased by 45% in L-ascorbic acid-supplemented keratinocyte
      cultures, indicating protection against cell death (p < 0.05). L-Ascorbic acid
      was able to downregulate IL-1alpha mRNA expression in both UVA-irradiated and
      nonirradiated cells; however, IL-6 mRNA expression remained unaffected. The
      secretion of these cytokines was reduced nearly to normal in the presence of L
      ascorbic acid. These findings indicate a major cell-protective effect of L
      ascorbic acid on UVA-induced lipid peroxidation and the secretion of pro
      inflammatory cytokines by UVA-irradiated human keratinocytes.

PMID- 9036930
TI  - Differential expression of the calpactin I subunits annexin II and p11 in
      cultured keratinocytes and during wound repair.
AB  - Transforming growth factor beta1 (TGF-beta1) is an important modulator of skin
      morphogenesis and cutaneous wound repair. To gain insight into the mechanisms of
      TGF-beta1 action in the skin, we used the differential display RT-PCR technique
      to identify genes that are regulated by this factor in cultured human
      keratinocytes. We obtained several partial cDNA clones. One of them was identical
      to the 3'-end of p11, the small and regulatory subunit of the calpactin I complex
      [(annexin II)2(p11)2]. RNase protection and northern blot analysis revealed
      specific regulation of expression of both subunits of this heterotetrameric
      protein (p11 and annexin II) by TGF-beta1 as well as by other growth factors,
      although the time course and degree of induction or suppression were different
      for each gene. Furthermore, we analyzed p11 and annexin II expression in normal
      and wounded skin. Both p11 and annexin II mRNAs were found in the dermal and
      epidermal compartments of normal human skin. Immunohistochemical studies
      demonstrated the presence of p11 at equally high levels in all layers of normal
      epidermis and in the hyper-proliferative epithelium at the wound edge. By
      contrast, annexin II expression was high in the basal layer of normal epidermis
      but low in the suprabasal layers and in the hyper-proliferative epithelium at the
      wound edge, suggesting a differentiation-specific regulation of this calpactin I
      subunit. The differential expression and regulation of p11 and annexin II
      subunits in keratinocytes suggest the existence of different ratios of monomeric
      versus p11-complexed annexin II that might be associated with different cellular
      functions.

PMID- 9036931
TI  - Transfection with aFGF cDNA improves wound healing.
AB  - Somatic gene therapy is a potentially useful strategy for the delivery of growth
      factors or cytokines to enhance wound healing. Experimental excisional and
      incisional wounds in impaired-healing diabetic mice (db/db) were treated with
      aFGF and with a plasmid coding for aFGF. A eukaryotic expression plasmid composed
      of the Hst signal peptide sequence in-frame with the human aFGF sequence was
      used. Transfection of tissues was accomplished either by direct plasmid uptake or
      by uptake facilitated with cationic liposomes. The results show that the closure
      of excisional wounds was significantly accelerated (p < 0.05) by topical
      application of human recombinant aFGF or by transfection with the aFGF plasmid
      but not by vehicle or control plasmid not containing the aFGF sequence. In
      incisional wounds, aFGF or transfection with the plasmid significantly increased
      the wound-breaking strength compared to their corresponding controls (p < 0.05).
      Quantitative histology of the plasmid-treated incisional wound sections revealed
      improved wound quality. The transcription of mRNA from human aFGF cDNA in the
      incisional wound tissue extracts was confirmed by RT-PCR, and the expressed aFGF
      was detected by immune dot blot and immunohistochemistry assays. The transfection
      was a transient process with a peak at 9 d in db/+ (littermates of the diabetic
      mice) incisional wounds, at 36 d in db/db incisional wounds, and at 27 d in db/db
      excisional wounds. Cells transfected with human aFGF occupied up to 6.4% of the
      transectional area in the wound sites. Thus, aFGF gene delivery resulted in both
      gene expression and a functional improvement in healing.

PMID- 9036932
TI  - Intrinsically aged epidermis displays diminished UVB-induced alterations in
      barrier function associated with decreased proliferation.
AB  - Ultraviolet (UV) irradiation of the skin induces a variety of responses in the
      epidermis, including sunburn cell formation, epidermal hyperplasia, and a dose
      dependent permeability barrier abnormality, an effect that appears to be
      dependent upon both UVB-induced hyperplasia and T-cell activation. Since
      intrinsically aged epidermis displays decreased epidermal turnover, diminished
      inflammatory response to various stimuli, including UVR, and impaired immune
      function, we investigated the effects of UVB on both epidermal barrier function
      and proliferation in hairless mice of increasing chronologic age (27, 61, and 90
      wk). After a single UVB exposure (0.15 J/cm2 7.5 MED), a barrier abnormality
      developed (i.e., increased transepidermal water loss; TEWL), after a delay of >
      or = 48 h, regardless of age. In young mice (27 wk old), TEWL levels peaked at 72
      96 h (9.9-fold over untreated controls), whereas increased epidermal
      [3H]thymidine incorporation preceded the peak TEWL increase (i.e., approximately
      570% increase over controls at 48 h). In contrast, the UVB-induced increased in
      both TEWL and DNA synthesis were significantly diminished, with decreased
      epidermal hyperplasia evident, in intrinsically aged versus young mouse
      epidermis. Baseline epidermal thickness decreased with animal age (i.e., 16.8 +/-
      3.1 vs. 27.9 +/- 0.7 microm for 90- vs. 27-wk-old animals, respectively; p <
      0.02), suggesting that the diminished barrier response with aging reflects an
      attenuation of events subsequent to initial UVB exposure, rather than an increase
      in the UV dose delivered. These results demonstrate that (i) murine epidermis
      becomes less sensitive to UVB-induced barrier alterations with age and (ii)
      decreased DNA synthesis after UVB correlates with the age-related decrease in
      barrier dysfunction.

PMID- 9036933
TI  - Keratin 17 gene expression during the murine hair cycle.
AB  - Keratin 17 (K17) expression is currently considered to be associated with
      hyperplastic or malignant growth of epithelial cells. The functions of this
      keratin in normal skin physiology and the regulation of its gene expression,
      however, are still unclear. As one possible approach to further explore K17
      functions, we have studied the differential patterns of mouse K17 (MK17)
      transcription during the murine hair cycle by means of in situ hybridization,
      using a digoxigenin-labeled riboprobe. Cycling hair follicles in the skin of
      C57BL/6 mice were found to be the only skin structures expressing MK17 under
      physiologic conditions. MK17 transcripts were constantly observed throughout all
      hair cycle stages in the suprainfundibular outer root sheath (ORS). The MK17
      expression was also evident in the isthmus part of the ORS, where it was
      expressed weakly and was spatially restricted during telogen, with an increase in
      early anagen and stable expression during mid- and late anagen, localizing to the
      zone of so-called trichilemmal keratinization. In addition, in early anagen, a
      group of epithelial cells in or next to the bulge region stained weakly for MK17.
      With progressing anagen development, MK17 expression in this region increased and
      was consistently localized to keratinocytes at the advancing front of the
      emerging epithelial hair bulb. In mid- and late anagen, this zone of MK17
      expression spread along the proximal ORS, with a maximal level of expression in
      the innermost cell layer of the ORS. Overall, these findings provide data on the
      MK17 expression profile of normal murine skin and demonstrate hair-cycle
      dependent regulation of MK17 expression.

PMID- 9036934
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCCD) affects keratin 1 and keratin 17 gene
      expression and differentially induces keratinization in hairless mouse skin.
AB  - The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes
      chloracne in humans by mechanisms that are as yet poorly understood. Because TCDD
      is known to affect keratinocyte differentiation in vitro, we have studied TCDD
      dependent morphologic changes and the expression of murine keratin 1 (MK1;
      differentiation associated) and keratin 17 (MK17; presumably hyperproliferation
      associated) in HRS/J hr/hr hairless mouse skin. TCDD (0.2 microg in acetone)
      applied topically to the dorsal skin caused epidermal acanthosis and
      hyperkeratosis of the dermal cysts as well as an involution of the utricles and
      the sebaceous glands. By means of in situ hybridization with digoxigenin-labeled
      riboprobes of sections from untreated and vehicle (control)-treated skin, we
      localized MK1 mRNA to the epidermal spinous cell compartment. MK17 transcripts
      were detected only in the derivatives of the hair follicle-utricle epithelium and
      dermal cysts. No spatial overlap was observed between MK1 and MK17 expression.
      After TCDD application, MK17 was newly expressed in the upper spinous cell layers
      of the interfollicular epidermis, although it was suppressed in the involuting
      utricles. In contrast, MK1 expression in the interfollicular epidermis was not
      affected by TCDD. Furthermore, MK1 expression was induced in the epithelium of
      the utricle remnants and in some dermal cysts. These data suggest that increased
      keratinization of the part of the follicular epithelium corresponding to the
      dermal cyst epithelium of hairless mice most probably explains the pathogenesis
      of TCDD-induced chloracne. The results demonstrate, furthermore, that TCDD can
      differentially affect keratinocyte differentiation in vivo as well as in vitro.

PMID- 9036935
TI  - The high-affinity receptor for IgE is the predominant IgE-binding structure in
      lesional skin of atopic dermatitis patients.
AB  - While the skin of most patients with atopic dermatitis (AD) is known to contain
      IgE-bearing cells, the contribution of the various IgE-binding structures to this
      phenomenon is not fully understood. To address this issue, we eluted cell-bound
      IgE from cryostat sections of lesional AD skin by acid treatment and performed
      reconstitution experiments with IgE in the absence or presence of reagents
      directed against the currently known IgE-binding structures. We found that
      incubation of acid-treated sections, with either chimeric or serum IgE, resulted
      in the appearance of sizable numbers of anti-IgE-reactive cells. This cellular
      IgE loading could be entirely prevented by preincubation of the sections with the
      anti-Fc epsilonRI alpha MoAb 15-1 but not with either antibodies against Fc
      epsilonRII/CD23 and Fc gammaRII/CD32 or with alpha-lactose. To exclude the
      possibility that acid treatment of tissue sections may have adversely influenced
      the IgE-binding capacity of IgE receptors other than Fc epsilonRI, we performed
      an identical series of experiments on AD skin samples that, as an exception, were
      essentially devoid of anti-IgE-reactive cells. Again, no IgE loading was detected
      when these sections were preincubated with anti-Fc epsilonRI alpha MoAbs. In
      contrast, preincubation of the sections with alpha-lactose and/or MoAbs against
      Fc epsilonRII/CD23 or Fc gammaRII/CD32 did not affect IgE loading. Together with
      the observations that anti-Fc epsilonRI alpha-reactive and IgE-binding cells are
      largely overlapping populations and include cells of the Langerhans
      cell/dendritic cell lineage, mast cells, and a few dermal dendrocytes and
      eosinophils, our results demonstrate that Fc epsilonRI is the predominant and,
      perhaps, the only biologically relevant IgE-binding structure on histogenetically
      and functionally diverse cell populations of AD skin.

PMID- 9036937
TI  - Primers for exon-specific amplification of the KRT5 gene: identification of novel
      and recurrent mutations in epidermolysis bullosa simplex patients.
AB  - The KRT5 and KRT14 genes encode the proteins keratin 5 and 14, respectively,
      which are the primary structural components of the 10-nm intermediate filaments
      of the mitotic epidermal basal cells. A single mutation in either gene can
      disrupt the keratin intermediate filament cytoskeleton, resulting in the skin
      fragility and blistering that is characteristic of the group of inherited
      disorders known as epidermolysis bullosa simplex. We have established a mutation
      detection system that facilitates KRT5 gene analysis from leukocyte genomic DNA,
      obviating the need for a skin sample or keratinocyte culture for cDNA synthesis.
      KRT5 intronic regions that flanked each exon were sequenced and sets of facing
      intronic primers were designed for specific amplification of each of the nine
      KRT5 exons. Direct sequencing of KRT5-amplified exons identified three novel
      missense mutations. One mutation recurred in two unrelated patients with sporadic
      EBS. This glutamate to lysine substitution (E477K), located in the highly
      conserved KLLEGE motif at the end of the central rod domain, is the third
      recurrent mutation identified in dominant epidermolysis bullosa simplex disease.
      The corresponding glutamate in keratin 2e was previously reported to be
      frequently mutated in ichthyosis bullosa of Siemens, suggesting that this highly
      conserved residue may be a potential mutational hot spot in other type II
      keratins or nonkeratin intermediate filament proteins.

PMID- 9036936
TI  - HECA-452+ T cells migrate through superficial vascular plexus but not through
      deep vascular plexus endothelium.
AB  - The skin is nourished by two interconnected vascular systems, the superficial
      vascular plexus coursing just beneath the epidermis and the deep vascular plexus
      located above the subcutaneous tissue. Skin inflammatory T cells in diseases,
      such as psoriasis or dermatitis, strikingly aim for the superficial vascular
      plexus without involving the deep vascular plexus, and the infiltrating T cells
      bear a distinct phenotype expressing the cutaneous lymphocyte-associated antigen,
      which is recognized by mAb HECA-452. We wanted to know whether HECA-452+
      lymphocytes indeed are able to distinguish between superficial and deep vascular
      plexus homing sites. Employing the hu-SCID mouse model grafted with human skin
      and human T cells, as described previously, we developed a new skin-grafting
      strategy providing superficial and deep vascular plexus skin specimens placed
      separately onto the same mouse. Fourteen days after allogeneic human T cell
      grafting, both human skin sites were densely infiltrated by human T cells, but
      only T cells within the superficial vascular plexus, but not within the deep
      vascular plexus, expressed the cutaneous lymphocyte-associated antigen. IL-2 and
      IFN-gamma expression and allogeneic vessel destruction were present within both
      superficial and deep vascular plexus skin. This model provides direct evidence
      that expression of a specific homing receptor is indeed able to direct lymphocyte
      traffic, not only to a distinct organ but also to a distinct vascular bed within
      one organ.

PMID- 9036938
TI  - A new keratin 2e mutation in ichthyosis bullosa of Siemens.
AB  - Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin condition
      with features similar to epidermolytic hyperkeratosis (EH). Clinical symptoms are
      characterized by mild hyperkeratosis with an acral distribution. Histology shows
      epidermolysis of upper spinous and granular cells, whereas ultrastructurally,
      tonofilaments form perinuclear aggregates. IBS has been linked to the type II
      keratin cluster on chromosome 12q, and K2e mutations have recently been
      identified in IBS patients. We have studied genomic DNA from two IBS families and
      in both cases heterozygous point mutations were found in the 2B helical domain of
      K2e. One family had an established mutation in codon 493 (E493K), whereas the
      other had an unreported mutation in the adjacent codon (E494K). Both mutations
      were confirmed by allele-specific PCR. These data reinforce the hypothesis that
      mutations in the TYRKLLEGEE motif of the 2B helix are deleterious to keratin
      filament network integrity and provide further evidence for the involvement of
      K2e mutations in IBS.

PMID- 9036939
TI  - A novel dinucleotide mutation in keratin 10 in the annular epidermolytic
      ichthyosis variant of bullous congenital ichthyosiform erythroderma.
AB  - Annular epidermolytic ichthyosis has recently been delineated as a distinct
      clinical phenotype within the spectrum of epidermolytic keratinization disorders.
      The pattern of inheritance of the disorder is consistent with an autosomal
      dominant mode of transmission. Here we report a second incidence of this disorder
      in a family with two affected generations. The proband suffered from bullous
      ichthyosis and had bouts of disease activity associated with the development of
      numerous annular and polycyclic erythematous, hyperkeratotic plaques on the trunk
      and the proximal extremities. Histologic examination showed the typical pathology
      of epidermolytic hyperkeratosis, and ultrastructural analysis revealed abnormal
      keratin filament networks and tonofilament clumping with a perinuclear
      distribution. Molecular analysis revealed a novel tandem CG to GA 2-bp mutation
      in the same allele of keratin 10 in affected individuals, resulting in an
      arginine to glutamate substitution at residue 83 (R83E) of the 2B helical
      segment. We conclude that annular epidermolytic ichthyosis should be considered a
      variant of bullous congenital ichthyosiform erythroderma.

PMID- 9036940
TI  - Is CTLA-4 a master switch for peripheral T cell tolerance?
AB  - The CD28/CTLA-4 and B7 families of cell surface molecules regulate a complex
      pathway of T cell signals that profoundly affect peripheral T cell responses. On
      the one hand, CD28/B7-mediated T cell costimulation is essential for the
      development and maintenance of T cell responses. In contrast, the prevailing data
      suggest that the engagement of CTLA-4 with the same B7 ligands down-regulates the
      initiation and progression of immune responses. This commentary examines the role
      of CTLA-4-mediated signaling in the regulation of the immune response, leading to
      the hypothesis that the CTLA-4/B7 interaction plays an essential role in the
      establishment of peripheral self-tolerance as well as the regulation of normal T
      cell immunity.

PMID- 9036941
TI  - Down-modulation of c-myc expression induces apoptosis of B lymphocyte models of
      tolerance via clonal deletion.
AB  - Whereas overexpression of the c-myc gene was found to promote apoptosis in
      fibroblasts, myeloid, and T cells, physiologic cell death of immature B cell
      lymphomas correlated with a drop in c-myc expression. Here, the author reviews
      recent evidence demonstrating that inhibition of c-myc expression activates
      apoptosis of B cell models of clonal deletion and that rescue from apoptosis by
      CD40 ligand leads to maintenance of c-Myc levels. A model of differential
      functional expression of the c-myc gene is discussed.

PMID- 9036942
TI  - Inhibition of CPP32-like proteases prevents granzyme B- and Fas-, but not
      granzyme A-based cytotoxicity exerted by CTL clones.
AB  - The perforin-facilitated entry of granzymes in target cells is a major mechanism
      used by CTL to induce cell death. It has been reported that granzyme B can cleave
      and activate the apoptotic cysteine protease p32 (CPP32)/Yama and its homologues
      in vitro. However, the mechanism for granzyme-based cytolysis exerted by intact
      CTL remains unclear. In the present work, we have used anti-CD3 mAb-redirected
      lysis of Fas-negative L1210 cells by CTL clones as a model to study
      perforin/granzyme-based cytotoxicity separately from the contribution of the
      Fas/Fas ligand system. N-acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO), a
      specific inhibitor of CPP32-like proteases, completely prevented the former type
      of lysis in 3-h assays, but not in long-term (16-h) assays. A combination of Ac
      DEVD-CHO and the granzyme A inhibitor IGA (7-(phenyl-ureido)-4-chloro-3-(2
      isothioureidoethoxy)-isocoumarin) inhibited long-term cytolysis. 3,4
      Dichloroisocoumarin, a serine-protease inhibitor that efficiently inhibits
      granzyme B and poorly inhibits granzyme A, had similar effects as Ac-DEVD-CHO on
      anti-CD3 mAb-redirected lysis of L1210 cells. On the other hand, Fas-based
      cytolysis exerted by the same CTL clones on Fas-transfected L1210 cells
      (L1210Fas) was inhibited completely by Ac-DEVD-CHO, irrespective of the
      incubation time. These results suggest that granzyme B- and Fas-based
      cytotoxicity exerted by CTL clones converge at the level of CPP32-like protease
      activation, while granzyme A acts via a different, still undefined, pathway. We
      also demonstrate that perforin/granzyme-based cytolysis occurs without increase
      in the cellular ceramide content, ruling out the contribution of the
      sphingomyelinase pathway to this mechanism of cell death.

PMID- 9036943
TI  - Biochemical analysis of p120/130: a protein-tyrosine kinase substrate restricted
      to T and myeloid cells.
AB  - T cell activation is mediated by a cascade of intracellular events involving
      protein-tyrosine kinases and their substrates. p56(lck) and p59(fyn) are protein
      tyrosine kinases that associate with CD4/CD8 and the TCRzeta/CD3 complex,
      respectively. We previously reported the appearance of a protein doublet at 120
      and 130 kDa that preferentially associates with p59(fyn) and undergoes tyrosine
      phosphorylation upon receptor ligation. In this paper, we demonstrate that
      p120/130 is a novel protein that is restricted in expression to T cells,
      thymocytes and myeloid cells. Internal peptide sequencing and immunoblotting
      using an anti-p120/130 antisera showed that p120/130 is a unique protein that is
      distinct from p130(cas) and p125(cbl). By contrast, p120 and p130 shared similar
      peptide patterns and are structurally related. Alkaline phosphatase digestion of
      precipitates showed that they are not related due to phosphorylation. p120/130
      was found to associate constitutively with a 55-kDa protein of unknown identity,
      but which is distinct from p56(lck) and Shc. p120/130 also undergoes a unique
      kinetics of phosphorylation and associates with the Ag receptor in response to
      TCR ligation. In keeping with the association with p59(fyn), T cells from
      p59(fyn)-negative mice exhibit reduced phosphorylation of the protein. p120/130
      therefore represents a novel TCR associated intracellular molecule with potential
      to play a role in T cell signaling.

PMID- 9036944
TI  - Sequestration of p56(lck) by gp120, a model for TCR desensitization.
AB  - Ligation of the CD4 receptor by HIV envelope glycoprotein gp120 inhibits T cell
      activation and signaling through the TCR complex. Recent reports suggest CD4
      ligation by gp120 + anti-gp120 Abs uncouples protein tyrosine kinases (PTKs) from
      the TCR signal-transduction cascade. This finding and other observations led us
      to hypothesize that the effects of gp120 are mediated through p56(lck), a PTK
      noncovalently associated with CD4. To test this hypothesis, we first examined the
      kinetics of gp120/anti-gp120-induced TCR signaling defects in the Jurkat T cell
      line. Pretreating cells with gp120/anti-gp120 for 1 to 4 h before stimulation
      prevented TCR-directed PTK activation. Coincident with TCR desensitization,
      pretreatment with gp120/anti-gp120 also decreased the amount of p56(lck) that
      could be immunoprecipitated from the Nonidet P-40 detergent-soluble fraction of
      cellular lysates, while simultaneously increasing the recovery of p56(lck) from
      the Nonidet P-40 detergent-insoluble fraction (or cytoskeleton). To assess the
      potential role of the actin in this process, experiments were conducted in the
      presence of cytochalasin D. Cytochalasin D restored TCR signaling in cells
      previously desensitized with gp120/anti-gp120 and prevented translocation of
      p56lck from the Nonidet P-40 detergent-soluble fraction of cell lysates.
      Furthermore, p56(lck) was found to coimmunoprecipitate with anti-actin. These
      data suggest that gp120/anti-gp120 may inhibit TCR signaling by sequestering
      p56(lck) to the cytoskeleton.

PMID- 9036945
TI  - B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity
      but retains CTLA4 binding: implications for induction of antitumor immunity to T
      cell tumors.
AB  - The B7 family of costimulatory molecules provides the second signal necessary for
      activation of T cells. In the absence of the second signal, responding T cells
      become anergic. Although predominantly expressed on professional APCs, recent
      evidence shows that the B7 molecules are also expressed on T cells. To study the
      functions of B7 molecules on T cells, we transfected murine B7.1 (CD80) and B7.2
      (CD86) cDNAs into the EL4 T cell thymoma cell line and examined the transfectants
      for their ability to costimulate T cell proliferation in vitro and to induce
      antitumor immunity in vivo. Here we show that although EL4-B7.1 cells costimulate
      T cells and induce tumor regression, EL4-B7.2 transfectants failed to costimulate
      T cell proliferation or induce tumor regression. To understand the cellular basis
      for this difference, we examined the binding of EL4-B7.1 and EL4-B7.2 to CTLA4
      and CD28. Whereas EL4-B7.1 cells bound both CTLA4-Ig and CD28-Ig, EL4-B7.2
      transfectants preferentially bound CTLA4-Ig, but not CD28-Ig. Similar binding
      data were obtained with freshly isolated murine T cells, which have been shown to
      constitutively express B7.2. Our data suggest, therefore, that B7.2 expressed on
      T cells may not costimulate but instead inhibit the T cell response by
      preferential binding to CTLA4.

PMID- 9036946
TI  - Phosphorylation of the NC-1.1 receptor and regulation of natural cytotoxicity by
      protein kinase C and cyclic GMP-dependent protein kinase.
AB  - Natural cytotoxicity (NC) against cancer involves receptor-ligand interactions
      between lymphohemopoietic cells that mediate NC against tumor cells. The only
      candidate for a receptor on cells mediating NC is NC-1.1, identified using mAb
      1C4. In this study we showed that mAb 1C4 blocked NC-1.1+ cell conjugation to
      WEHI-164 tumor cells, indicating that NC-1.1 is a surface protein required for
      cell-cell interaction. Affinity-purified NC-1.1 was a 45-kDa monomeric protein.
      It was a good in vitro substrate for cyclic GMP (cGMP)-dependent protein kinase
      (PKG) and protein kinase C (PKC) and a relatively poor substrate for cAMP
      dependent protein kinase (PKA). Phosphopeptide mapping revealed one
      phosphopeptide phosphorylated by PKG and PKA, and two additional peptides
      phosphorylated by PKC. Phosphorylation by PKG or PKA abolished phosphorylation at
      the PKC sites, while coincubation of NC-1.1 with both PKG and PKC reduced
      phosphorylation of all sites. NC-1.1 was also a phosphoprotein after
      immunoprecipitation from intact spleen cells and its phosphorylation was
      increased after cell stimulation with PKC or PKG activators (phorbol esters or 8
      bromo-cGMP). The possible consequences of intracellular signaling were tested in
      functional assays for NC. Phorbol ester activation of spleen cells increased NC,
      while 8-bromo-cGMP and 8-bromo-cAMP had little effect. However, coincubation with
      both phorbol ester and either 8-bromo-cGMP or 8-bromo-cAMP virtually abolished NC
      without affecting cell conjugation. These results suggest that NC-1.1 is a
      receptor for a ligand on certain tumor cells and reveal that key intracellular
      signaling pathways involving PKC, PKG, and PKA interact to effect a coordinated
      control of NC.

PMID- 9036947
TI  - B7-CD28/CTLA-4 costimulatory pathways are required for the development of T
      helper cell 2-mediated allergic airway responses to inhaled antigens.
AB  - We have previously demonstrated that the development of allergen-induced airway
      hyperresponsiveness in a murine model is CD4+ T cell dependent. In the present
      study, we examined the role of the B7/CD28-CTLA4 costimulatory T cell activation
      pathway in the pathogenesis of allergen-induced airway hyperresponsiveness in
      this murine model. Sensitized A/J mice develop significant increases in airway
      responsiveness, bronchoalveolar lavage eosinophils, serum IgE levels, and Th2
      associated cytokine production following aspiration challenge with OVA.
      Administration of CTLA4-Ig either before Ag sensitization or before pulmonary Ag
      challenge abolished Ag-induced airway hyperresponsiveness and pulmonary
      eosinophilia. Examination of cytokine protein levels in the bronchoalveolar
      lavage showed a significant decrease in the level of the Th2 cytokine, IL-4,
      after CTLA4-Ig treatment either before sensitization or before challenge, with no
      significant change in the concentration of the Th1 cytokine, IFN-gamma. Further,
      the Ag-specific Ab isotypes IgG1 and IgE were significantly decreased in animals
      treated with CTLA4-Ig before challenge, while there was no significant change in
      the IgG2a Ab isotype. These data demonstrate that administration of CTLA4-Ig is
      effective in ablating allergen-induced airway dysfunction concomitant with a
      significant reduction in the Th2 response. We conclude that B7/CD28-CTLA-4
      costimulation is required for the development of many of the immunologic and
      physiologic features of asthma, possibly by promoting a pathologic type 2
      associated response.

PMID- 9036948
TI  - Overexpression of c-fos inhibits down-regulation of a cyclin-dependent kinase-2
      inhibitor p27Kip1 in splenic B cells activated by surface Ig cross-linking.
AB  - Splenic B cells activated by surface Ig (sIg) cross-linking transiently express
      the c-fos gene within 0.5 h and then enter into S phase of the cell cycle within
      48 h. To investigate a role of c-fos in cell cycle progression, we used splenic B
      cells from IFN-alphabeta-inducible c-fos transgenic mice (Mx-c-fos). In the
      absence of IFN, the cell cycle progression of Mx-c-fos B cells stimulated with
      anti-IgM Ab was similar to that in control B cells. The cell cycle was arrested
      in G1 phase when we added IFN to the culture within 12 h after anti-IgM Ab
      stimulation, suggesting that overexpression of c-fos until mid-G1 phase perturbs
      activation of the cell cycle regulatory machinery. In control B cells, cyclin E
      and cdk2 were induced within 24 to 48 h after stimulation, and this induction was
      accompanied by down-regulation of a cdk2 inhibitor p27Kip1. As a consequence of
      these activation processes, cdk2 kinase activity was induced in B cells in the
      late G1 phase. However, kinase activity was not detected in Mx-c-fos B cells,
      presumably because the down-regulation of p27 was perturbed. These data suggest
      that c-Fos can negatively control cell cycle regulatory machinery in sIg
      stimulated B cells.

PMID- 9036949
TI  - Differential T cell signaling induced by antagonist peptide-MHC complexes and the
      associated phenotypic responses.
AB  - Certain changes in TCR contact residues have been shown to have profound effects
      on the capacity of a peptide Ag to stimulate a T cell response. Although some of
      these changes apparently lead to a complete loss of the ability to interact with
      the TCR, others result in partial agonist activity (e.g., cytokine production
      without proliferation) or antagonist activity (i.e., the capacity to inhibit the
      engagement to the TCR by Ag). We show MHC class II-restricted antagonist activity
      was associated with a differential pattern of early tyrosine phosphorylation
      events that was characterized by a preponderance of phosphorylation of low
      molecular mass TCRzeta and the failure to phosphorylate Zap-70. These early
      tyrosine phosphorylation patterns are the same as those previously described for
      partial agonists. Thus, a partial agonist phenotype such as anergy induction
      cannot be ascribed in a causal manner to this pattern of tyrosine
      phosphorylation. We further extend the studies of signal transduction elicited by
      agonist and antagonist peptides by characterizing differential recruitment of Zap
      70 associated with TCRzeta isoforms and differential phosphorylation of p120
      proto-oncogene c-Cbl. Another early event following TCR engagement by Ag, down
      modulation of the TCR, was studied with antagonist peptides. We show that
      antagonist peptides do not cause TCR down-modulation. This failure may represent
      a mechanism by which antagonists inhibit antigen-mediated stimulation of T cells.

PMID- 9036950
TI  - TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by
      inhibiting class II transactivator messenger RNA expression.
AB  - Recently, a non-DNA binding protein, class II transactivator (CIITA), has been
      shown to be required for constitutive and IFN-gamma-inducible class II MHC
      transcription. The cytokine TGF-beta inhibits IFN-gamma-induced class II MHC
      expression at the transcriptional level. In this study, we provide evidence that
      TGF-beta blocks IFN-gamma-induced CIITA mRNA accumulation. TGF-beta down
      regulates class II MHC and CIITA mRNA accumulation in human astroglioma and
      fibrosarcoma cell lines, but TGF-beta does not destabilize the CIITA message,
      suggesting an effect at the transcriptional level. In cells that stably
      overexpressed CIITA, leading to a constitutive class II MHC-positive phenotype,
      the inhibitory effect of TGF-beta on class II MHC was abrogated, but the cells
      remained responsive for expression of TGF-beta-inducible genes. Cell lines that
      possessed defects in TGF-beta signaling also became refractory to inhibition of
      IFN-gamma-induced CIITA and class II MHC expression. Our data indicate that TGF
      beta suppresses IFN-gamma-induced class II MHC expression by inhibiting
      accumulation of CIITA mRNA.

PMID- 9036951
TI  - Phenotypes and invariant alpha beta TCR expression of peripheral V alpha 14+ NK T
      cells.
AB  - A novel subset of peripheral T cells, peripheral NK T cells, is found to be a
      major population comprising 5% of splenic T and 40% of bone marrow T cells. The
      majority of peripheral NK T cells are characterized by the expression of an
      invariant TCR-alpha encoded by V alpha 14/J alpha 281 with a one nucleotide N
      region. Moreover, a specific reduction of V alpha 14+ NK T cells has been
      demonstrated to be tightly associated with various autoimmune diseases,
      indicating their decisive role in autoimmune disease development. In this study,
      we investigated the phenotypes of peripheral V alpha 14+ NK T cells and their TCR
      beta repertoire. Peripheral V alpha 14+ NK T cells, comprise two populations,
      i.e., small and large sized cells, at an equal frequency, belonged to the CD4-
      CD8- fraction, and are heat stable antigen(bright), macrophage-1bright,
      B220bright, CD45RBdim, and Mel-14dim, but CD5-, distinct from thymic NK T cells.
      TCR-beta analysis clearly showed that peripheral V alpha 14+ NK T cells utilized
      two to three dominant invariant TCR-beta, such as V beta 8.2 D beta J beta 2.5/V
      beta 7 D beta J beta 2.1 in the spleen and liver, V beta 8.2 D beta J beta 2.5/V
      beta 8.3 D beta J beta 2.2/V beta 7 D beta J beta 2.6 in the bone marrow, and V
      beta 7 D beta J beta 2.1/V beta 3 D beta J beta 1.2 in intestinal intraepithelial
      lymphocytes. Judging from the unusual surface phenotypes, such as heat stable
      antigen, macrophage-1, B220, CD45RBdim, and Mel-14dim, which are known to be T
      cell activation markers, peripheral V alpha 14+ NK T cells may always be
      activated under physiologic conditions, resulting in the oligoclonal expansion of
      V alpha 14+ NK T cells with different invariant TCR-beta in different peripheral
      organs. The unique features of V alpha 14+ NK T cells are discussed.

PMID- 9036952
TI  - The DNA-dependent protein kinase catalytic subunit (p460) is cleaved during Fas
      mediated apoptosis in Jurkat cells.
AB  - The DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase linked to
      DNA repair and V(D)J recombination. It is composed of a 460-kDa catalytic subunit
      (DNA-PKcs) and a 70/86-kDa heterodimeric regulatory component that is identical
      with the human autoantigen Ku. The regulatory subunit targets the catalytic
      subunit to the free ends of dsDNA breaks. Since apoptosis is associated with
      internucleosomal chromatin fragmentation and creation of dsDNA breaks, we
      examined whether the biochemical amounts of either DNA-PKcs or Ku changed during
      apoptosis mediated by the cell surface receptor Fas. We found that the catalytic
      subunit was cleaved into several smaller polypeptides early in apoptosis. In
      contrast to DNA-PKcs, Ku was neither cleaved nor decreased in amount during
      apoptosis. We then extended our in vivo results to a cellfree system. Cytosolic
      extracts derived from apoptotic cells were able to cleave DNA-PKcs into
      polypeptides of sizes identical with those seen in vivo, and this cleavage was
      inhibited by the cysteine protease inhibitors iodoacetamide and N-ethylmaleimide.
      Furthermore, DNA-PKcs was cleaved in vitro by purified apopain (CPP32), but not
      IL-1beta-converting enzyme. Cleavage was also inhibited by the specific
      tetrapeptide DEVD (amino acids 2709-2712 of the DNA-PKcs sequence), suggesting a
      candidate position for protease action. Finally, we found that the catalytic
      activity of DNA-PKcs was decreased in apoptotic cells. We conclude that DNA-PKcs
      is subject to selective cleavage by proteases during apoptosis. Cleavage of DNA
      PKcs may represent a mechanism for regulating the function of DNA-dependent
      kinase during programmed cell death.

PMID- 9036953
TI  - Reciprocal regulation of CD30 expression on CD4+ T cells by IL-4 and IFN-gamma.
AB  - Prior studies have implicated CD30 as a marker for Th2 cells, but the mechanism
      that underlies this correlation was unknown. We show here that CD30 was expressed
      on activated CD4+ T cells in the presence of IL-4. In the absence of endogenously
      produced IL-4, however, even Th2 lineage cells lost CD30 expression. Thus, CD30
      is not an intrinsic marker of Th2 cells, but is inducible by IL-4. CD30 was also
      found to be down-regulated by IFN-gamma. Committed Th1 effector cells do not
      express CD30, although differentiating Th1 lineage cells temporarily express
      CD30. The transient expression of CD30 on differentiating Th1 lineage cells was
      mainly the result of endogenously produced IL-4 induced by IL-12. Culture of IL
      12-primed cells under conditions that reverse the phenotype (Ag plus IL-4)
      resulted in two cell populations based upon their ability to express CD30. One
      population responded to IL-4 upon restimulation and became a CD30-positive, Th0
      like cell population, while the other remained CD30 negative and synthesized only
      IFN-gamma. Thus, CD30 expressed on CD4+ T cells reflected the ability of CD4+ T
      cells to respond to IL-4.

PMID- 9036954
TI  - Monoclonal antibodies specific for beta 7 integrin and mucosal addressin cell
      adhesion molecule-1 (MAdCAM-1) reduce inflammation in the colon of scid mice
      reconstituted with CD45RBhigh CD4+ T cells.
AB  - Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is an adhesion protein
      expressed on endothelium in mucosal tissues that has been shown to play an
      important role in the selective homing of lymphocytes to intestinal mucosa and
      associated lymphoid tissue. To determine whether MAdCAM-1 or its ligand alpha 4
      beta 7 would be appropriate targets for therapeutic intervention in gut
      associated inflammation, we tested the ability of rat mAbs specific for beta 7
      integrin and MAdCAM-1 to inhibit chronic colonic inflammation in scid mice
      reconstituted with CD4+ T cells enriched for the CD45RBhigh subpopulation. Abs
      specific for beta 7 and MAdCAM-1 blocked recruitment of lymphocytes to the
      colitic colon, and more importantly, these Abs significantly reduced the severity
      of colonic inflammatory disease in this animal model. Therefore, the adhesive
      interactions mediated by alpha 4 beta 7 and MAdCAM are intimately involved in
      leukocyte recruitment to gut in chronic inflammatory disease and may be relevant
      therapeutic targets for patients with inflammatory bowel disease.

PMID- 9036955
TI  - MUC18/MCAM (CD146), an activation antigen of human T lymphocytes.
AB  - Extravasation and tissue infiltration of leukocytes and metastatic tumor cells
      require the regulated expression and function of adhesive and pro-proteolytic
      surface molecules. We demonstrate here that human T cells, upon activation, neo
      express the melanoma metastasis-associated surface molecule MUC18/melanoma cell
      adhesion molecule (MCAM). Expression of MUC18/MCAM (CD146) on T cells could be
      identified with two mAbs (541-10B2 and 541-2E5) obtained after immunization with
      HUT102 T cells and found to react with activated T cells. The specificity of our
      mAbs for MUC18/MCAM (CD146) was revealed by 1) definition of the appropriate
      molecular mass of approximately 110 kDa unreduced and 120 kDa reduced, 2)
      reactivity of mAbs with MUC18/MCAM (CD146) cDNA-transfected mouse L cells, 3)
      conclusive crosswise immunoblotting experiments with MUC18/MCAM (CD146)-specific
      mAbs, and 4) N-terminal amino acid sequencing of precipitated protein. In vitro
      activation by PHA caused neo-expression of MUC18/MCAM (CD146) on peripheral blood
      T cells within 1 day of stimulation, reaching a maximum on day 3. In vivo
      expression of MUC18/MCAM (CD146) was confirmed on CD3+ T cells infiltrating
      delayed-type hypersensitivity lesions of the skin, on synovial fluid T cells of
      rheumatoid arthritis patients, and on distinct T leukemia cells. MUC18/MCAM
      (CD146) cell surface expression on activated T cells is mirrored by the presence
      of specific mRNA. Leukocytes of healthy donors do not show significant MUC18/MCAM
      (CD146) expression. The finding that MUC18/MCAM (CD146) is also expressed on
      activated T cells might suggest that this adhesion molecule is involved in the
      extravasation and/or homing of activated T cells.

PMID- 9036956
TI  - The nonpolymorphic MHC class II isotype, HLA-DQA2, is expressed on the surface of
      B lymphoblastoid cells.
AB  - The more centromeric of the two human MHC class II DQA genes, DQA2, has not
      previously been shown to express a protein product. However, its high degree of
      sequence similarity to DQA1, the fact that it is highly evolutionarily conserved,
      and the recent demonstration of its transcription in some cell lines suggest that
      a DQA2 alpha-chain may be expressed. Polyclonal anti-peptide antisera were
      generated and shown to be specific for DQA2 in Western blotting of Triton X-114
      preparations of B lymphoblastoid cell lines. DQA2 expression is variable,
      although always at least threefold less than that of DQA1, and is found in all
      haplotypes examined. Immunoprecipitations of biotin-labeled cell surface proteins
      reveal that DQA2 appears at the cell surface. In keeping with others' findings,
      no evidence for an expressed DQB2 beta-chain was found, prompting investigation
      of the means by which DQA2 gains access to the cell surface. Antisera specific
      for allotypic and isotypic MHC class II beta-chains were used in sequential
      immunoprecipitation experiments to search for a beta-chain partner for DQA2, and
      a transfectant system was established in an attempt to promote pairing of DQA2
      with a selected DQB1 (*0501) chain. In neither case was DQA2 found to dimerize
      with an MHC class II beta-chain. Despite this, DQA2 is capable of forming a
      complex with invariant chain.

PMID- 9036957
TI  - Lack of type 2 T cell-independent B cell responses and defect in isotype
      switching in TNF-lymphotoxin alpha-deficient mice.
AB  - TNF is implicated in in vitro Ig production, but its role in vivo is not clearly
      defined. Our previous studies had shown that TNF-LT alpha double-deficient mice
      have defective IgM and IgG primary Ab responses to the T cell-dependent (TD) Ag
      SRBC. We now extend these studies to secondary responses and to T cell
      independent (TI) B cell responses. Injections of the TD Ag SRBC did not induce
      germinal center formation in the spleen of TNF-LT alpha-deficient mice.
      Associated with the morphologic defect, there was a defective IgG Ab response and
      a secondary hyper-IgM response to the TD Ag in TNF-LT alpha-deficient mice. The
      response to the TI Ag type 2 DNP-alanyl-glycyl-glycyl-Ficoll was essentially
      absent in TNF-LT alpha-deficient mice, while that to the TI Ag type 1 TNP-LPS was
      significantly reduced only for IgG2b isotype. Transplantation of bone marrow
      cells from wild-type mice into irradiated TNF-LT alpha-deficient mice restored
      the formation of splenic germinal centers and corrected the IgM and IgG responses
      to both TD and TI Ags. These data suggest that TNF and/or LT alpha signaling are
      critically required for germinal center formation and for the IgM and IgG
      responses to both TD and TI type 2 Ags.

PMID- 9036958
TI  - Dendritic cells that process and present nominal antigens to naive T lymphocytes
      are derived from CD2+ precursors.
AB  - Dendritic cells (DC) are potent APC that, in mature form, can be distinguished
      from other mononuclear cells on the basis of their distinct morphology, absence
      of lineage markers, and dense expression of MHC and costimulatory molecules.
      While comparing different DC preparation methods, we observed that DC derived
      from cultured PBMC that had been depleted of CD2+ cells before culture were
      functionally distinct from DC derived from PBMC that had not been depleted of
      CD2+ cells. Thus, both types of DC stimulated allogeneic T cells to proliferate
      in the MLR, but only DC derived from CD2+ precursors could sensitize naive T
      cells to soluble Ags such as keyhole limpet hemocyanin and HIV gp160
      glycoprotein. Subsequent studies confirmed the existence of CD2+ and CD2- DC
      precursor populations among HLA-DRbright, lineage-negative PBMC. Immediately
      after their isolation, these populations were morphologically similar to one
      another by light and electron microscopy, and neither had substantial Ag
      presenting activity. After culture for 24 to 48 h with supernatant from PHA
      activated PBMC, both populations developed dendrites, formed clusters with T
      cells, and stimulated allogeneic T cell responses in the MLR as well as
      autologous T cell responses to tetanus toxoid, a recall Ag. However, CD2+ DC
      precursors alone gave rise to APC that presented soluble Ags to naive CD4+ T
      cells, a property that could be inhibited by Abs to CD4, CD11a, and CD28 on T
      cells or CD86 on DC. The expression of CD54 and CD86 on CD2+ DC precursors was
      increased markedly after their culture and differentiation, while the expression
      of these molecules on CD2- DC precursors was not remarkably changed. These
      findings reveal the existence of two functionally distinct populations of DC,
      each derived from a phenotypically distinct precursor present in monocyte
      depleted peripheral blood.

PMID- 9036959
TI  - Nonclassical behavior of the mouse CD1 class I-like molecule.
AB  - The mouse CD1 (mCD1) molecule is a class I-like molecule that is encoded outside
      of the MHC. We show here that mCD1 shares several properties with Ag-presenting
      class I molecules, including a requirement for beta2-microglobulin for stable
      cell-surface expression in T lymphocyte transfectants and thymocytes. mCD1 is
      also capable of binding to mouse CD8alphabeta heterodimers participating in the
      activation of CD8+ T cells in a manner similar to classical class I molecules.
      However, mCD1 surface expression is not decreased at high temperatures in cells
      that lack the transporter associated with Ag processing (TAP), including both RMA
      S and Drosophila melanogaster cells. The data indicate that mCD1 does not require
      TAP to be expressed in a stable fashion at the cell surface. We speculate that
      the ability of mCD1 to reach the cell surface in transporter-deficient cells may
      reflect its ability to present a distinct set of ligands. The properties of mCD1
      described here can account, in part, for the selection of the diverse populations
      of T cells that are known to be mCD1 reactive.

PMID- 9036960
TI  - Direct thymic involvement in anterior chamber-associated immune deviation:
      evidence for a nondeletional mechanism of centrally induced tolerance to
      extrathymic antigens in adult mice.
AB  - Recent reports have suggested that the dichotomy between central (thymic) and
      peripheral T cell tolerance is not absolute and that self-tolerance in perinatal
      animals may also involve the intrathymic generation and release to the periphery
      of Ag-specific immunoregulatory T cells. We have expanded this concept to include
      tolerance to non self Ags administered extrathymically to adult animals. In this
      study, we use the anterior chamber-associated immune deviation (ACAID) to
      demonstrate that central regulation of acquired peripheral tolerance can be
      induced in adult mice by the intraocular administration of low doses of nonself
      Ag. The results show that adult thymectomy prevents the inhibition of
      trinitrophenol (TNP)-specific delayed-type hypersensitivity, which normally
      occurs after injection of TNP-BSA into the anterior chamber (AC) of the eye.
      Thymocytes obtained from mice 1 to 3 days, but not 5 to 7 days, after AC
      injection of TNP-BSA or BSA alone specifically transfer inhibition of delayed
      type hypersensitivity to mice primed with the homologous Ag. The latter
      observation, when correlated with the time of onset of ACAID, suggests that
      immunoregulatory T cells are formed in the thymus within 24 h and are exported to
      the peripheral lymphoid tissues between 2 and 5 days after AC injection of Ag.
      Immunomagnetic separation of thymocytes revealed that the immunoregulatory
      activity resides within the minor subset of CD4-, CD8-, TCR-alphabeta+ cells,
      previously postulated to induce fas ligand-mediated apoptosis and Th1 to Th2
      immune deviation. Hence, the present study identifies ACAID as a prototypical
      model of centrally induced, nondeletional tolerance to extrathymic nonself Ags.

PMID- 9036961
TI  - Anti-human class I MHC antibodies induce apoptosis by a pathway that is distinct
      from the Fas antigen-mediated pathway.
AB  - 5H7, an anti-human class I MHC mAb that recognizes a monomorphic determinant of
      the alpha3 domain, profoundly inhibits T lymphocyte activation. The present study
      was designed to determine the role of programmed cell death in 5H7-mediated
      immune suppression. Incubation of PBMC with 5H7 mAb induced a marked reduction in
      viable cell recovery (VCR) of T cells (<10% VCR), NK cells (<1% VCR), and B cells
      (<1% VCR). In addition, 5H7 inhibited proliferation and VCR of JY, DBS-521, and
      BevD tumor lines as well as cells transfected with HLA-B27. Morphologic changes
      characteristic of apoptosis were induced by 5H7, including cell membrane
      blebbing, cytoplasmic vacuolization, condensation of nuclear chromatin, and
      nuclear fragmentation. Furthermore, DNA fragmentation was demonstrated in 5H7
      treated PBMC using a TdT-mediated end-labeling (TUNEL) technique. 5H7, but not
      anti-Fas mAb, induced apoptosis of cell lines derived from patients with Niemann
      Pick disease that lack acidic sphingomyelinase activity. In addition, induction
      of cell death by 5H7 was not inhibited by IL-1beta-converting enzyme (ICE)
      inhibitors under conditions that fully suppressed Fas-mediated apoptosis. These
      findings suggest that signal transduction through "classical" human class I MHC
      molecules induces apoptosis by a Fas-independent pathway that does not require
      acidic sphingomyelinase, is independent of ICE protease, and may represent a
      unique pathway of cell death in human lymphocytes.

PMID- 9036962
TI  - Activation of the aryl hydrocarbon receptor/transcription factor and bone marrow
      stromal cell-dependent preB cell apoptosis.
AB  - In the absence of known endogenous ligands, investigators have exploited
      ubiquitous environmental pollutants, including polycyclic aromatic hydrocarbons,
      to gain insight into the physiologic functions of the aryl hydrocarbon (dioxin)
      receptor/transcription factor (AhR). AhR ligands induce cell transformation and
      steroid-like immunosuppression, suggesting a role for the AhR in regulation of
      cell growth and/or function. However, mechanisms through which the AhR influences
      cells in general and lymphocytes in particular remain unresolved. A murine model
      of B cell development was created to: 1) examine a role for the AhR in
      immunosuppression; 2) define mechanisms of AhR ligand immunosuppression; 3)
      characterize AhR expression in preB cells, in bone marrow stromal cells that
      support preB cells, or in primary bone marrow B cells; and 4) determine if AhR
      ligands suppress lymphopoiesis by acting directly on preB cells or indirectly via
      the microenvironment, as represented by bone marrow stromal cells. Results
      indicate that: 1) low doses (> or = 10(-8) M) of the prototypic AhR ligand, 7,12
      dimethylbenz[a]anthracene (DMBA), induce preB cell apoptosis in 12 to 24 h; 2)
      alpha-naphthoflavone, an AhR and cytochrome P-450 inhibitor, blocks DMBA-induced
      apoptosis; 3) AhR mRNA and functional AhR protein are expressed at high levels in
      bone marrow stromal cells (little or no AhR is present in preB cell lines), and
      4) preB cells maintained in rIL-7 do not undergo DMBA-induced apoptosis unless
      cultured with stromal cells. Results underscore the regulatory role played by
      bone marrow stromal cells in lymphopoiesis and support the hypothesis that the
      AhR effects immunosuppression by inducing stromal cells to deliver a death signal
      to lymphocytes.

PMID- 9036963
TI  - Both resting and activated B lymphocytes expressing engineered peptide-Ig
      molecules serve as highly efficient tolerogenic vehicles in immunocompetent adult
      recipients.
AB  - To test the potential for genetically transferring foreign sequences into
      autologous cells for specific modulation of immunity, we have generated
      transgenic mice that express an engineered peptide-IgG construct in the
      peripheral B cell compartment. B cells from these mice express and can be
      stimulated to secrete a murine IgG1 chain grafted with residues 12-26 from
      bacteriophage A cI repressor protein in-frame at the heavy chain N terminus. As
      expected, 12-26-IgG transgenic mice are profoundly tolerant to the peptide at
      both the T and B cell levels. Importantly, the injection of transgenic whole
      spleen, purified B cells, or even bone marrow cells into normal, immunocompetent
      adults results in profound peptide-specific T cell tolerance, as well as partial
      B cell tolerance. Injection of LPS-activated peptide-Ig-expressing B cells was
      uniquely effective at diminishing an ongoing humoral immune response typical of
      both Th1 and Th2 help. Since fixed transgenic B cells were tolerogenic, this
      suggests that secretion of the fusion protein is not required for tolerogenicity.
      These results show that an engineered self Ig, as well as B lymphocytes
      expressing epitopes from such a fusion protein, can regulate both cellular and
      humoral immune responses. Moreover, these studies provide the basis for
      expressing foreign epitopes on engineered IgG for the induction of gene
      transferred tolerogenesis in autoimmune states.

PMID- 9036964
TI  - Dominance of a single peptide bound to the class I(B) molecule, Qa-1b.
AB  - One of the hallmarks of class I(A) molecules is their ability to bind and present
      a wide array of peptides to CD8 T cells. This diversity is consistent with their
      ability to restrict a variety of pathogenic peptide epitopes as well as elicit
      strong transplantation responses. In contrast, class I(B) molecules appear to be
      involved in presentation of pathogenic epitopes to a relatively lesser extent as
      well as play a minor role in transplantation responses. Here we have examined the
      peptides bound and presented by the class I(B) molecule Qa-1b in order to
      determine if their diversity was similar to that reported for class I(A) Ags.
      First, we show that bulk-cultured anti-Qa-1b CTL predominantly recognize a single
      peptide (Qdm) derived from the leader segment of class I(A) alloantigens. These
      CTL are peptide specific and reflect the activity of previously described CTL
      clones. Second, we find approximately 4.6 x 10(4) copies of the Qdm peptide/cell.
      Most of the peptide is Qa-1b associated since the recovery of this peptide from
      anti-Qa-1b immunoprecipitates is approximately 75% of that seen in whole cell
      extracts and no detectable activity is observed in Kb or Db extracts from H-2b
      lymphoblasts. Third, the expression of Qa-1b on lymphoblasts is approximately 1
      to 1.25 x 10(4) molecules/cell indicating that the Qdm peptide must be derived
      from both cell membrane and intracellular compartments. Finally, examination of
      the diversity of peptides associated with Qa-1b as determined by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry indicates few
      detectable peptide species associated with this molecule. Taken together, Qa-1b
      appears to predominantly bind a single peptide species that is recognized by
      alloreactive CD8 T cells. This feature may account, in part, for the class I(B)
      properties of this molecule.

PMID- 9036965
TI  - Structural consequences of humanizing an antibody.
AB  - We have determined the crystal structure of the Fv fragment of a humanized anti
      hen eggwhite lysozyme Ab (HuLys). This molecule is a composite of known
      structures: complementarity-determining regions (CDRs) were from the mouse anti
      lysozyme Ab D1.3, heavy chain framework regions were from the human myeloma
      protein NEW, and the light chain framework regions were consensus sequences
      similar to the Bence Jones protein REI. HuLys crystallized in space group
      P4(3)2(1)2, with two Fv molecules in the crystallographic asymmetric unit. The
      structure was solved by molecular replacement, using a composite of the parent
      structures as a search model. The resolution of the structure was 2.87 A, with an
      R factor of 22%. There were several unanticipated structural similarities and
      differences between HuLys and the mouse and human structures. The framework
      regions of HuLys were as close or closer in conformation to D1.3 than to the NEW
      or REI protein, despite overwhelming sequence identity with the human framework
      regions. The effect was most pronounced at the CDR-framework junction, showing
      that the CDRs can induce structural changes in framework residues, having the net
      effect in HuLys of reconforming the framework into a conformation more like D1.3.
      In the combining site, the grafted CDRs retained conformational equilibria seen
      in D1.3, demonstrating that humanizing can be applied to Abs that bind Ags
      through isomeric equilibrium or induced fit mechanisms. In addition, HuLys showed
      systematic differences from D1.3 that resembled domain rotations reported for
      other Abs. However, the V(H)-V(L) interface itself was unaffected, and the
      apparent movement was actually caused by rearrangements distant from this
      surface.

PMID- 9036966
TI  - Definition of a large region of RAG1 that is important for coimmunoprecipitation
      of RAG2.
AB  - Interaction between the RAG1 and RAG2 proteins is probably critical for V(D)J
      recombination. Using a coimmunoprecipitation assay, we define a large region of
      RAG1 (amino acids 504-1008) that is sufficient for interaction with RAG2. This
      region comprises the C-terminal half of the RAG1 protein, and is within the
      region defined as the recombinationally active core. Deletion of either of two
      regions of RAG1 (amino acids 504-570 or 850-1008) causes a loss of interaction
      with RAG2. Loss of coimmunoprecipitation is also seen with RAG1 core proteins
      containing deletions of smaller stretches of amino acids (amino acids 506-511 or
      545-550), emphasizing the importance of this region of RAG1 in forming a complex
      with RAG2. A variety of other small deletion mutations within the amino acid
      region 504-1008 also decrease coimmunoprecipitation of RAG2 with RAG1, indicating
      that much or all of this region is important for complex formation.

PMID- 9036967
TI  - Delineation of the amino acid residues involved in transcytosis and catabolism of
      mouse IgG1.
AB  - The MHC class I-related receptor, FcRn, is involved in both the transcytosis of
      serum gamma-globulins (IgGs) and in regulating their serum persistence. The
      interaction site of FcRn on the Fc region of rodent IgG has been mapped to
      residues at the CH2-CH3 domain interface using site-directed mutagenesis and x
      ray crystallographic analyses. In the current study, the role of individual
      residues (H310, H433, and N434) at this interface in mediating the Fc-FcRn
      interaction has been investigated using recombinant, mutated Fc hinge fragments
      derived from mouse IgG1. In addition, two highly conserved Fc histidines (H435
      and H436) have been mutated to alanine, and the resulting mutated Fc hinge
      fragments were analyzed in both transcytosis and pharmacokinetic studies in mice
      and in competition binding assays using recombinant, soluble FcRn. The analyses
      indicate that mutation of H310, H435, and, to a lesser extent, H436 to alanine
      results in reduced activity of the Fc hinge fragments in both in vivo and in
      vitro assays. Thus, in addition to the previously defined role of 1253 in the
      FcRn-IgG interaction, these histidines play a key role in mediating the functions
      conducted by this Fc receptor. The effects of these mutations on binding of Fc
      hinge fragments to staphylococcal protein A have also been analyzed and
      demonstrate a partial, but not complete, overlap of the FcRn and staphylococcal
      protein A interaction sites on mouse IgG1.

PMID- 9036968
TI  - A three-domain T cell receptor is biologically active and specifically stains
      cell surface MHC/peptide complexes.
AB  - We have expressed in bacteria a single-chain T cell receptor (scTCR) with
      specificity for an HIV gp120-derived peptide bound to the murine MHC-I molecule,
      H-2Dd. This scTCR consists of V alpha covalently linked to the VbetaCbeta domains
      that was solubilized, refolded, and purified in high yield. Specific binding of
      the scTCR to MHC/peptide complexes was demonstrated by surface plasmon resonance,
      with a Kd of 2 to 8 x 10(-6) M. This scTCR specifically inhibited T cell
      activation, and stained cell surface MHC/peptide complexes as measured by
      cytofluorimetry. The preservation of binding specificity by such a three-domain
      scTCR suggests that this structure is sufficient for specific MHC/peptide
      recognition and that this strategy will be of general use as applied to other
      TCR.

PMID- 9036969
TI  - Chromatin structure of the lymphocyte Fc epsilon receptor gene (CD23):
      identification of an upstream transcriptional enhancer.
AB  - The low-affinity receptor for IgE of lymphocytes, Fc epsilonRII or CD23, is
      likely to play pivotal roles in normal B cell differentiation, EBV induced B cell
      immortalization and regulation of the IgE response to allergens and to parasitic
      infection. We have studied the expression of CD23 mRNA in several cell contexts.
      In EBV-infected Burkitt lymphoma cells, we have confirmed that high levels of
      expression are determined largely at the level of gene transcription by
      performing nuclear run-on transcription analyses and stability determinations of
      CD23 mRNA in actinomycin D chase experiments. In an effort to define the
      complexity of the potential modes of activation of CD23 in various cell contexts,
      we have studied the chromatin structure of the gene as determined by the pattern
      and distribution of DNasel hypersensitive sites in CD23. We have found that,
      unlike the results obtained in many analogous systems, there is no distinct
      pattern of hypersensitive sites that uniquely correlates with high levels of CD23
      transcription in various B lineage cell lines. Instead, we found a complex
      pattern that suggests that CD23 expression is regulated by trans-acting
      regulatory factors whose activity is dependent upon the stage of cellular
      differentiation as well as the cell lineage. By determining whether the DNA
      encompassing these hypersensitive sites contains transcriptional enhancer
      activity, we discovered a novel enhancer that functions in an EBV-dependent
      fashion and encompasses a 384-bp segment that lies 3.7 kb upstream from the
      transcription start site.

PMID- 9036970
TI  - Prominence of beta 2-microglobulin, class I heavy chain conformation, and tapasin
      in the interactions of class I heavy chain with calreticulin and the transporter
      associated with antigen processing.
AB  - Newly synthesized class I heavy (H) chain/beta 2m heterodimers awaiting peptides
      in the endoplasmic reticulum are associated with the transporter associated with
      Ag processing (TAP). We present evidence here that calreticulin, but not
      calnexin, displays steady state association with class I/TAP complexes. To
      separate the ability of beta 2m to bind with TAP and calreticulin from that of H
      chain, we studied human cell lines that lack expression of beta 2m or H chain.
      Little if any H chain was detected in association with TAP and calreticulin in
      the beta 2m- cell line Daudi. By contrast, high levels of beta 2m are found with
      TAP and calreticulin in the H chain-deficient cell line LCL 721.221, even after
      preclearance of the trace amount of class IB protein expressed by this cell line.
      Thus, beta 2m appears to bind TAP in the absence of H chain, providing an elegant
      mechanism to retain beta 2m in the endoplasmic reticulum at the site of peptide
      loading. To investigate whether other molecules participate in the binding of
      beta 2m and H chain to TAP and calreticulin, we analyzed the deletion mutant cell
      line LCL 721.220, which lacks tapasin. In 721.220, TAP and calreticulin are not
      associated with each other. Also, in these cells, H chain/beta 2m are not
      associated with TAP, but H chain and a low level of beta 2m are associated with
      calreticulin. These results suggest that tapasin is an obligatory mediator of the
      assemblage of calreticulin/H chain/beta 2m with TAP.

PMID- 9036971
TI  - Conjugation of human Fc gamma in closed-hinge or open-hinge configuration to
      Fab'gamma and analogous ligands.
AB  - We describe a method for linking human normal Fc gamma1, via stable thioether
      bonds emerging from its hinge, to any molecule expressing a free sulfhydryl (SH)
      group. The Fc hinge may be closed by a disulfide (SS) bond or left open.
      Preparation begins with reduction of the Fc hinge to release four SH groups from
      its two parallel inter-gamma SS bonds. When the Fc is required in normal closed
      hinge configuration, one SH group is alkylated with N-ethylmaleimide under
      limiting conditions, and one of the inter-gamma SS bonds is reconstituted by SS
      interchange. The residual SH group, to be used for linking, is left as a 4
      dithiopyridyl group suitable for storage. When the Fc is required for conjugation
      the 4-dithiopyridyl is replaced by a metastable maleimidyl group, which reacts
      rapidly with SH on the partner molecule to form a tandem thioether link. If the
      partner is Ab Fab'gamma, linking to cysteines in the Fab'gamma hinge yields
      derivatives such as FabFc and FabFc2. Chimeric FabFc Abs (mouse Fab'gamma/human
      Fc gamma1) invoked cellular cytotoxicity in vitro, using human cell lines as
      targets and human lymphocytes as effectors, whether the Fc hinge was open or
      closed. The same Abs could kill the same targets by activating human complement,
      but only when the Fc hinge was closed. Both effector functions were enhanced by
      the presence of a second Fc in FabFc2. This method of Fc addition can be used to
      predict the performance of recombinant chimeric Abs and to provide novel
      molecular geometries.

PMID- 9036972
TI  - AML1A and AML1B can transactivate the human IL-3 promoter.
AB  - The AML1 gene encodes several transcription factors, including AML1A and AML1B,
      which bind to DNA via a TGT/cGGT consensus sequence that is found in several
      promoters, including the human IL-3 promoter. We performed cotransfection
      experiments in T cells, and demonstrated that although AML1A lacks a putative
      transactivation domain, it can transactivate the IL-3 promoter nearly as
      effectively as AML1B, a known activator. A consensus AML1 binding site (TGTGGT),
      located in the previously identified DNase I footprint region A of the human IL-3
      promoter (extending from bp -165 to -128), and a sequence similar to the
      consensus binding site (TGTGGG), located in footprint region B (bp -55 to -42),
      specifically bind AML1 proteins in gel shift assays. The affinity for the TGTGGG
      sequence was much less than that for the TGTGGT sequence, and mutating the TGTGGG
      sequence did not alter the IL-3 promoter activity, whereas mutation of the
      consensus binding site decreased the basal promoter activity and nearly
      eliminated transactivation by AML1A and AML1B. The AML1/ETO fusion protein,
      generated by the t(8;21) translocation, repressed IL-3 promoter activity,
      although the AML1 portion of AML1/ETO (amino acids 1-177) lacked transcriptional
      regulatory activity and did not bind to DNA in vitro. The 60- to 177-amino acid
      portion of AML1 readily bound DNA, suggesting that the first 59 amino acids may
      function as an inhibitory domain for DNA binding. Demonstration of the
      transactivation by AML1A and localization of a putative inhibitory binding domain
      suggest additional complexity within this family of transcription factors.

PMID- 9036973
TI  - Both innate and acquired immunity to Listeria monocytogenes infection are
      increased in IL-10-deficient mice.
AB  - IL-10-deficient mice were highly resistant to Listeria monocytogenes during the
      course of infection. An increased innate immunity was suggested by reduced
      bacterial burdens (as much as 50-fold) early (days 2 and 3) in the infection, as
      compared with control mice. In addition, in vitro stimulation of both IL-10
      deficient peritoneal exudate cells and spleen cells with heat-killed Listeria
      resulted in a dramatically enhanced proinflammatory cytokine response (e.g., IL
      12, IFN-gamma, TNF-alpha, IL-1alpha, and IL-6). During later stages of a primary
      Listeria infection, the reduced bacterial burden in the infected organs of IL-10
      deficient mice was accompanied by decreased tissue damage and earlier clearance
      of the pathogen, as well as a stronger Th1 polarization. The absence of IL-10 did
      not influence membrane-bound factors that stimulate Th cell responses,
      demonstrated by the finding of normal MHC class II, B7.1, and B7.2 surface
      expression on F4/80+ macrophages in vivo. IL-10-deficient mice were also more
      resistant to a secondary infection, accompanied by an enhanced Th1 response. The
      results presented in this work demonstrate that the absence of IL-10 augments
      innate and acquired immunity during primary and secondary L. monocytogenes
      infection by up-regulating proinflammatory type 1 cytokine responses. The
      resulting protective Th1 responses lead to an effective reduction of bacterial
      growth and tissue destruction and to an earlier clearance of the bacteria. The
      physiologic role of IL-10 during L. monocytogenes infection studies is discussed
      and compared with pathogenic infections that induce a more systemic cytokine
      response in IL-10-deficient mice.

PMID- 9036974
TI  - Predominant appearance of NK1.1+ T cells producing IL-4 may be involved in the
      increased susceptibility of mice with the beige mutation during Salmonella
      infection.
AB  - C57BL/6 mice with the beige mutation (beige mice) showed a high susceptibility to
      infection with Salmonella choleraesuis compared with C57BL/6 (B6) control mice,
      as assessed by bacterial number in the peritoneal cavity and the liver. The
      appearance of NK1.1+ CD3- NK cells was significantly suppressed, while NK1.1+ T
      cells were increased in the peritoneal cavity of beige mice after Salmonella
      infection. The expression level of IL-4 mRNA was much higher in freshly isolated
      NK1.1+ T cells of the infected beige mice, but the expression level of IFN-gamma
      mRNA was lower than that in the infected control mice. The NK1.1+ T cells
      produced more IL-4 in response to TCR alphabeta cross-linking, whereas IFN-gamma
      production upon TCR triggering was significantly impaired in the beige mice
      compared to that in the control mice. Furthermore, the generation of Salmonella
      specific Th1 cells producing IFN-gamma was significantly inhibited in the
      peritoneal cavity of beige mice after Salmonella infection. However,
      administration of anti-IL-4 neutralizing mAb to beige mice during salmonellosis
      restored the generation of Salmonella-specific Th1 cells and decreased the
      susceptibility to Salmonella. These results suggested that the predominant
      activation of NK1.1+ T cells producing IL-4 over those producing IFN-gamma may be
      at least partly involved in the poor generation of Salmonella-specific protective
      Th1 cells, resulting in the increased susceptibility of beige mice to Salmonella
      infection.

PMID- 9036975
TI  - Different T helper cell types and antibody isotypes generated by saline and gene
      gun DNA immunization.
AB  - Several routes and methods of DNA immunization have been shown to generate Ab, Th
      cells, and CTL responses. However, few studies have directly compared the immune
      responses generated by different routes and methods of DNA immunization.
      Utilizing an influenza hemagglutinin (H1)-expressing plasmid, we compared the
      immune response produced by saline injection of DNA into skin or muscle, and gene
      gun immunization of skin or muscle. We found that saline-DNA immunization raised
      a predominantly Th1 response with mostly IgG2a anti-H1 Ab, while gene gun DNA
      immunization produced a predominantly Th2 response with mostly IgG1 anti-H1 Abs.
      These distinct types of immune responses were generated by the method, not the
      route, of DNA immunization. The initial immunization established the Th cell-type
      of the immune response. The Th cell-type did not change with further DNA
      immunizations by the same or the alternate method, or after a viral challenge.
      The ability to generate different Th types was not due to differences in the
      doses of DNA used in saline and gene gun DNA immunization. These findings have
      important implications for vaccine design and studies of the mechanism of Th cell
      differentiation.

PMID- 9036976
TI  - The role of the CD28/B7 interaction in the regulation of NK cell responses during
      infection with Toxoplasma gondii.
AB  - We examined the role of the CD28/B7 interaction in regulation of NK cell
      activity. Cells transfected with B7 enhanced IL-12-induced production of IFN
      gamma by IL-2-activated, CD28+ NK cells, but not by resting CD28- NK cells. The
      ability of B7 transfectants to enhance NK cell production of IFN-gamma was
      dependent on the intracellular adhesion molecule-1/LFA-1 interaction and could be
      inhibited by TGF-beta, but not IL-10. Since IL-12-induced production of IFN-gamma
      by NK cells is associated with resistance to certain infections, we examined
      whether the CD28/B7 interaction regulated NK cell responses during infection.
      Infection of SCID mice with Toxoplasma gondii resulted in the appearance of a
      population of CD28+ NK cells, NK cell production of IFN-gamma, and increased NK
      cell cytolytic activity. Administration of CTLA4-Ig to SCID mice infected with T.
      gondii inhibited these latter two effects and resulted in a significant increase
      in parasite burden. The stimulus for CD28 expression by NK cells in SCID mice
      infected with T. gondii appeared to be independent of IL-2. However, mRNA for IL
      15, a cytokine with properties similar to those of IL-2, was detected in tissues
      of SCID mice infected with T. gondii. In vitro experiments demonstrated that IL
      15 could stimulate resting NK cells to express functionally active CD28 as well
      as enhance the production of IFN-gamma by SCID splenocytes stimulated with T.
      gondii. Together our data demonstrate that the interaction of CD28+ NK cells with
      B7 regulates NK cell production of IFN-gamma associated with resistance to
      infection and that IL-15 may be involved in these events.

PMID- 9036977
TI  - Early T cell unresponsiveness in mice with candidiasis and reversal by IL-2:
      effect on T helper cell development.
AB  - To investigate the role and effect of IL-2 in the genesis of Th1 and Th2
      responses to Candida albicans in vivo, we assessed the levels of IL-2 production
      and the Ag-specific proliferative response in mice with healing or nonhealing
      infection and the effects of IL-2 neutralization or administration on the course
      and outcome of infection and on the type of CD4+ Th immunity elicited. High
      levels of IL-2 production and Ag-specific proliferation in vitro correlated with
      disease progression in susceptible mice. In contrast, resolution of infection in
      resistant mice was accompanied by the induction of Ag-specific hyporesponsiveness
      and impaired IL-2 production. Progression of infection did not occur in
      susceptible mice treated with anti-IL-2 or anti-IL-2R mAbs; conversely, disease
      resolution was prevented in resistant mice treated with IL-2. CD4+ Th1 cell
      responses were present in BALB/c mice rendered resistant by IL-2 neutralization
      and CD4+ Th2 responses in mice rendered susceptible by IL-2 treatment. The
      presence of IL-2 restored Ag-specific responsiveness in vitro and correlated in
      vivo with the expansion of CD4+ MEL-149(low) cells capable of producing IL-2 and
      IL-4 both in vitro and in vivo as observed in adult thymectomized mice. These
      results indicate that production of IL-2 early in infection correlates with the
      induction of IL-4-producing CD4+ Th2 cells, while a transient loss of T cell
      responsiveness, such as IL-2 production, appears to be required for CD4+ Th1
      occurrence in mice with candidiasis.

PMID- 9036978
TI  - Lethal effect of recombinant human Fas ligand in mice pretreated with
      Propionibacterium acnes.
AB  - Fas ligand (FasL) is a type II membrane protein. Binding of FasL to its receptor,
      Fas, induces apoptosis. Matrix metalloproteinase cleaves the membrane-bound human
      FasL to yield the active soluble form. Here, we have produced a large amount of
      human soluble rFasL using the yeast, Pichia pastoris. The purified rFasL was
      found to be glycosylated and to exist as a trimer. The rFasL was effective in
      inducing apoptosis in a Fas-expressing T cell or a fibroblast cell line. The ID50
      of rFasL for mouse Fas-expressing T cells was about 0.5 ng/ml. The killing
      process with rFasL was quick. That is, >80% Fas-expressing mouse cells were
      killed within 1 h by a saturation concentration of human rFasL. Intravenous
      administration of 500 microg of human rFasL had a lethal effect in mice. When the
      mice were pretreated with Propionibacterium acnes, the subsequent injection of 30
      microg of human rFasL induced hepatic failure and killed the mice within 24 h.
      These results indicated that the soluble human FasL is active in inducing
      apoptosis in vitro and in vivo, and its deleterious effect may be strengthened in
      patients who are suffering from bacterial infection.

PMID- 9036979
TI  - Human mast cells activate fibroblasts: tryptase is a fibrogenic factor
      stimulating collagen messenger ribonucleic acid synthesis and fibroblast
      chemotaxis.
AB  - The effect of human mast cells on fibroblast activity was studied using an
      organotypic skin-equivalent culture system. Human mast cell-1 (HMC-1) cells were
      embedded in a collagen gel with neonatal dermal fibroblasts at a ratio of 1:4;
      keratinocytes then were allowed to stratify above this composite culture.
      Analysis of type a1(I) procollagen mRNA synthesis by in situ hybridization
      revealed a substantial increase in mRNA levels in the presence of mast cells and
      especially following degranulation, induced by calcium ionophore A23187.
      Tryptase, a major product of human mast cells, could substitute for mast cells in
      this culture system, up-regulating procollagen mRNA synthesis. Tryptase
      pretreated with the specific protease inhibitor bis(5-amidino-2-benzimidazo
      lyl)methane (BABIM) markedly attenuated the collagen mRNA up-regulation. Further
      studies revealed HMC-1 cell sonicates stimulated fibroblast chemotaxis and
      procollagen mRNA synthesis. Inhibition of HMC-1 sonicates with either BABIM or a
      neutralizing mAb against tryptase resulted in significant reduction of fibroblast
      chemotaxis and procollagen mRNA, implying that tryptase accounted for the
      majority of HMC-1 sonicate activity. Tryptase directly stimulated fibroblast
      chemotaxis with optimal concentrations between 10 pM and 1 nM. The maximal
      response of optimal concentrations of tryptase was comparable with the known
      fibrogenic factor, TGF-beta. Inhibition of tryptase with BABIM resulted in
      approximately 50% reduction in chemotactic activity. Additional studies revealed
      that tryptase (0.3-3 nM) stimulated procollagen mRNA synthesis in confluent
      monolayers of dermal fibroblasts.

PMID- 9036980
TI  - Regulation of brain-derived T cells during acute central nervous system
      inflammation.
AB  - The unique immunologic environment of the central nervous system (CNS) regulates
      most local inflammatory responses. In some circumstances, however, immune
      mediated injury to the brain can occur. To understand how lymphocytes are
      regulated within the CNS during an inflammatory response that does not produce
      immunopathology, we have studied T cells isolated from the brains of mice with
      Sindbis virus (SV) encephalitis. Even though they express activation markers,
      these T cells are arrested in the cell cycle and do not proliferate in vitro.
      Altered phosphorylation of the retinoblastoma gene product, a critical cell cycle
      regulator, appears to mediate this effect. Furthermore, while brain-derived T
      cells generate IFN-gamma, IL-4, and IL-10, these T cells are deficient in IL-2
      production compared with peripheral T cells. This pattern of cytokine production
      occurs in cells that do not activate NF-kappaB normally. When T cells producing
      both IL-2 and IFN-gamma are adoptively transferred into SV-infected mice, some of
      these cells traffic into the brain. Those that enter the brain selectively down
      regulate IL-2 production over time. Since normal brain lipids can inhibit IL-2
      production and T cell proliferation in vitro, these substances may mediate these
      same effects in vivo. Collectively, these data show that the local environment of
      the CNS during SV encephalitis exerts a complex regulatory effect on T cells that
      are recruited into the brain. We speculate that this effect serves to prevent
      excessive local T cell reactivity. Whether and how this regulation might fail in
      the setting of autoimmune neurologic disease remains to be explored.

PMID- 9036981
TI  - Cytokine and chemokine regulation of proMMP-9 and TIMP-1 production by human
      peripheral blood lymphocytes.
AB  - The production and activation of matrix-degrading proteinases such as the matrix
      metalloproteinases (MMP) by lymphocytes is likely to be an important factor in
      facilitating lymphocyte trafficking through the endothelial barrier and the
      extracellular matrix. Leukocyte infiltration into inflammatory sites occurs as a
      response to members of the chemokine superfamily and other inflammatory
      mediators. In the present study, highly purified leukocyte subpopulations were
      cultured with or without chemokines or cytokines, and their ability to express
      gelatinolytic MMPs and their inhibitors, the tissue inhibitors of
      metalloproteinase (TIMPs), was analyzed. In the absence of exogenous stimuli,
      purified CD4+ T lymphocytes produced similar quantities of proMMP-9 and elevated
      levels of TIMP-1 compared with PBMC, while purified CD8+ and CD3+ populations
      exhibited less MMP-9 and TIMP-1 activity. In comparison, CD56+ (NK) cells
      secreted barely detectable levels of proMMP-9 and TIMP-1. The secretion of proMMP
      9 by PBMC and purified CD3+, CD4+, and CD8+ lymphocytes was selectively modulated
      by beta chemokines and proinflammatory cytokines. ProMMP-9 secretion by CD3+ and
      CD4+, but not by CD8+ T cells was augmented in response to TNF-alpha and IL-1,
      and down-regulated by IFN-gamma, while macrophage inflammatory protein (MIP)
      1alpha, MIP-1beta, and RANTES (regulated upon activation and normally T cell
      expressed and secreted) (beta chemokines) up-regulated the secretion of proMMP-9
      by all of the lymphocyte subsets tested. These results demonstrate that a number
      of proinflammatory cytokines and chemokines differentially regulate proMMP-9
      secretion from purified CD4+ and CD8+ lymphocytes, while for purified CD3+ T
      cells (consisting of CD4+ and CD8+ cells in approximately a 2:1 ratio), a
      predominantly CD4+ lymphocyte response profile was demonstrated.

PMID- 9036982
TI  - Substance P-induced IL-12 production by murine macrophages.
AB  - Previous investigations in our laboratory have suggested that substance P (NK-1)
      receptor expression by macrophages contributes to the resistance against the
      intracellular bacterial pathogen, Salmonella. To investigate possible mechanisms
      for such resistance, macrophages were cultured with varying concentrations of a
      substance P agonist to investigate the ability of this neuropeptide to augment IL
      12 expression. The substance P agonist was a potent inducer of both IL-12p35 and
      IL-12p40 mRNA expression in cultured macrophages. The kinetics of this response
      were maximal within 6 h and could be observed with concentrations of substance P
      agonist as low as 0.1 nM. The nonpeptide, substance P receptor antagonist, CP96
      345, significantly blocked agonist-induced IL-12 mRNA expression, further
      demonstrating that this effect was mediated through an NK-1 receptor. Substance P
      agonist alone could stimulate substantial secretion of IL-12p40, but not IL
      12p70, by cultured macrophages. Thus, the substance P agonist had the ability to
      augment IL-12p35 and IL-12p40 mRNA expression, but not to increase IL-12p70
      secretion. Like IFN-gamma, we found that substance P could combine with LPS to
      significantly augment the secretion of bioactive IL-12p70. The costimulatory
      effects of substance P agonist plus LPS on IL-12 mRNA expression were additive;
      however, this combination resulted in synergistic secretion of IL-12p70 by
      macrophages. Together, these results demonstrate the ability of NK-1 receptors to
      signal IL-12 production by macrophages and suggest mechanisms for substance P
      induced modulation of cellular immunity.

PMID- 9036983
TI  - Contrasting responses to multiple chemotactic stimuli in transendothelial
      migration: heterologous desensitization in neutrophils and augmentation of
      migration in eosinophils.
AB  - At inflammatory sites in vivo, leukocytes may confront multiple, competing
      chemoattractive signals. We found significant differences between eosinophils and
      neutrophils in transendothelial chemotaxis to a chemoattractant diffusing from
      the lower chamber, when a chemoattractant that binds to another receptor is
      present at uniform concentration. The transendothelial migration of eosinophils
      to FMLP, C5a, RANTES, or MCP-3 was totally inhibited by the presence of the
      homologous chemoattractant, and only RANTES and MCP-3 showed mutual inhibition.
      C5a and to a lesser extent FMLP chemokinetically stimulated migration to RANTES
      and MCP-3, without stimulating random migration. Results with neutrophils
      contrasted. The presence of FMLP not only abrogated neutrophil transmigration to
      FMLP but also strongly decreased chemotaxis to C5a, IL-8, and Gro-alpha.
      Similarly, C5a inhibited neutrophil chemotaxis to IL-8 and Gro-alpha. IL-8 almost
      totally abrogated chemotaxis to Gro-alpha, but Gro-alpha only moderately
      inhibited chemotaxis to IL-8. Neither IL-8 nor Gro-alpha significantly inhibited
      transmigration to FMLP or C5a. Actin polymerization in eosinophils and
      neutrophils was desensitized by the same combinations of chemoattractants that
      desensitized chemotaxis. We conclude that eosinophils have at least three
      noninterfering receptor-signal transduction pathways for chemotaxis and actin
      polymerization. In contrast, the signaling pathways for FMLP, C5a, and IL-8/Gro
      alpha in neutrophils are heterologously cross-desensitized, with a hierarchy of
      resistance to competing signals of FMLP > C5a > IL-8 > Gro-alpha, in agreement
      with previous results in neutrophils on the Ca2+-mobilizing response. These
      results may have important implications for the behavior of these cell types in
      inflammatory sites.

PMID- 9036984
TI  - Impaired tyrosine phosphorylation and Ca2+ mobilization, but not degranulation,
      in lyn-deficient bone marrow-derived mast cells.
AB  - Signaling through the high affinity IgE receptor (Fc epsilon RI) on mast cells
      and basophils results in rapid increases in tyrosine phosphorylation on a number
      of proteins. Fc epsilon RI associates with two classes of the tyrosine kinases,
      the Src family kinases, such as Lyn, c-Yes, and c-Src, and the Syk kinase. In
      this work, using primary mast cells derived from wild-type (lyn +/+) and lyn
      deficient (lyn -/-) mice, we report that Lyn plays a part in signaling via Fc
      epsilon RI. Unlike lyn +/+ mast cells, cross-linking of Fc epsilon RI in lyn -/-
      mast cells failed to induce protein-tyrosine phosphorylation of various
      substrates, and evoked a delayed and slow Ca2+ mobilization. However,
      degranulation, adhesion, and production of cytokines occurred normally in lyn -/-
      mast cells. Our data suggest that the activity of the other Src family kinases,
      such as c-Src, can complement the role of Lyn in inducing most, but not all,
      biologic and biochemical responses to Fc epsilon RI cross-linking.

PMID- 9036985
TI  - An immunoregulatory role for neutrophils in CD4+ T helper subset selection in
      mice with candidiasis.
AB  - Granulocytes may serve immunoregulatory and effector roles in different limbs of
      the immune response to infection. Using live vaccine strain or virulent challenge
      in mucosal or systemic infection of mice with Candida albicans, we examined the
      effect of mAb-mediated depletion of neutrophils on the course of primary and
      secondary challenge and on development of CD4+ cell-dependent immunity. We
      obtained evidence of deleterious effects of neutrophil depletion occurring at the
      time of infection under all conditions of testing, both in naive and in
      previously immunized mice. In contrast, neutrophil depletion appeared to benefit
      the hosts late in the course of an overwhelming systemic infection. In an attempt
      to correlate neutrophil function with the nature of the T cell response, we
      tested the ability of neutrophils to produce cytokines associated with
      functionally distinct CD4+ Th cell responses to Candida. We found that
      neutrophils were endowed with the capacity to secrete IL-12 and IL-10 in vitro in
      response to the yeast. Neutrophil ablation early in the course of Th1-associated,
      self-limiting infection appeared to change the qualitative development of the T
      cell response, and rendered mice susceptible to infection. In addition to long
      recognized contributions to acute anti-candidal responses, these data suggest an
      important role for neutrophils both in initiation and in expression of Candida
      specific immunity.

PMID- 9036986
TI  - Regulation of IFN-alpha/beta, MxA, 2',5'-oligoadenylate synthetase, and HLA gene
      expression in influenza A-infected human lung epithelial cells.
AB  - The epithelial cells of the respiratory tract are the primary sites of virus
      replication in influenza A virus infections. We infected human alveolar
      epithelium-like A549 cells and fibroblast-like human fetal lung (HFL1) cells with
      a pathogenic influenza A virus (A/Beijing/353/89), and studied the kinetics of
      infection and the expression of host IFN-alpha/beta, MxA, OAS (2',5'
      oligoadenylate synthetase), and HLA class I and II genes. Viral mRNA and protein
      synthesis was clearly seen in virus-infected lung cells. A549 and HFL1 cells
      produced only small amounts of IFN-alpha/beta, whereas virus-infected macrophages
      produced type I IFN very efficiently. The kinetics of IFN-beta gene expression in
      A549 cells was rapid, as shown by reverse-transcriptase PCR, and IFN-beta mRNA
      expression levels correlated well to the kinetics of nuclear factor-kappa B
      transcription factor activation. In influenza A virus-infected A549 and HFL1
      cells, MxA gene induction was mediated by IFN-alpha/beta released into the cell
      culture supernatant, and was prevented by anti-type I IFN Abs. HLA class I Ag
      expression, which could be activated by IFN in noninfected A549 and HFL1 cells,
      was not induced in these cells by virus infection. The results suggest that type
      I IFN are essential for the activation of the antiviral response in lung
      epithelial cells.

PMID- 9036987
TI  - Nitric oxide, an autocrine regulator of wound fibroblast synthetic function.
AB  - Nitric oxide (NO) is synthesized in wounds, but its exact role and cellular
      source are not known. Wound fibroblasts (WF) are phenotypically characterized by
      increased collagen synthesis and contractility. We hypothesized that WF may be
      also phenotypically altered during wound healing to synthesize NO. WF were
      isolated from polyvinyl alcohol sponges implanted in male Lewis rats and
      harvested 10 days later. Proliferation in response to 10% fetal bovine serum was
      assessed by [3H]thymidine incorporation in a microculture system. A fibroblast
      populated collagen lattice was used for assaying contractility. Collagen
      synthesis was determined by measuring the collagenase-sensitive fraction of
      protein-incorporated [3H]proline. Fibroblasts were incubated in the presence or
      the absence of 0.5 mM S-methyl-isothio-uronium or 0.5 mM N-monomethyl-L-arginine,
      both competitive inhibitors of NO synthase. WF spontaneously synthesize and
      release NO (4.60 +/- 0.29 nmol nitrite/microg DNA/48 h). Normal dermal
      fibroblasts do not synthesize NO. WF NO synthesis was limited to the first and
      second passages postharvest and was inhibitable by S-methyl-isothio-uronium (96%)
      and N-monomethyl-L-arginine (84%). In vivo iNOS expression by WF was confirmed by
      in situ hybridization and immunohistochemistry. Inhibition of endogenous NO
      synthesis had no effect on fibroblast proliferation. However, fibroblast-mediated
      collagen contraction was enhanced (p < 0.01), and collagen synthesis was
      significantly decreased (p < 0.05) by inhibiting NO synthase. The data show that
      WF are phenotypically altered during the healing process to synthesize NO, which,
      in turn, regulates their collagen synthetic and contractile activities.

PMID- 9036988
TI  - Increased secretion of TNF-alpha by costimulation of mast cells via CD28 and Fc
      epsilon RI.
AB  - The present study unequivocally demonstrated the expression of CD28 on murine
      bone marrow-derived cultured mast cells and a mast cell line, MCP-5. Stimulation
      of surface CD28 molecules on mast cells with anti-CD28 mAbs induced tyrosine
      phosphorylation of cellular proteins, including several protein tyrosine kinases
      and their substrates, such as Itk/Emt (Emt), Btk, Syk, c-Cbl, Shc, and Vav. CD28
      stimulated tyrosine phosphorylation was followed by a rebound
      hypophosphorylation. Interestingly, CD28 stimulation alone elicited a low level
      secretion of TNF-alpha. On the other hand, cross-linking of the high affinity IgE
      receptor (Fc epsilon RI) on mast cells induces a set of activation events, i.e.,
      degranulation, secretion of eicosanoids, secretion of cytokines, and DNA
      synthesis. Concurrent stimulation of mast cells through CD28 enhanced Fc epsilon
      RI-induced TNF-alpha secretion in a dose-dependent manner. Together, the present
      data suggest a role for CD28-mediated costimulation of mast cells in the
      initiation and progression of allergic responses and other diseases.

PMID- 9036989
TI  - Activation of the phosphatidylinositol 3-kinase serine kinase by IFN-alpha.
AB  - During engagement of the type I IFN receptor, IRS-1 is phosphorylated on tyrosine
      and associates with the p85 regulatory subunit of the phosphatidylinositol (PI)
      3'-kinase, which is a dual-specificity enzyme possessing both lipid and serine
      kinase activities. We sought to determine whether treatment of cells with IFN
      alpha activates the PI 3'-kinase serine kinase. 32P-labeling experiments and
      phosphoaminoacid analysis of immunoprecipitated IRS-1 protein demonstrated that,
      in addition to tyrosine phosphorylation, IFN-alpha induces its phosphorylation on
      serine residues. In vitro kinase assays on alphaIRS-1 immunoprecipitates also
      demonstrated IFN-alpha-dependent serine phosphorylation of IRS-1, suggesting that
      the protein associates with an IFN-alpha-regulated serine kinase. Furthermore,
      IFN-alpha-dependent phosphorylation of IRS-1 was detected in in vitro kinase
      assays on alpha p85 immunoprecipitates, and was inhibited by pretreatment of
      cells with the specific PI 3'-kinase inhibitor wortmannin, consistent with a
      regulatory role of the PI 3'-kinase serine kinase on the phosphorylation of the
      protein. Treatment of cells with wortmannin also inhibited the phosphorylation of
      the p85 subunit of PI 3'-kinase and the type I IFN-regulated activation of the
      Map kinase, but had no inhibitory effect on the IFN-alpha-induced activation of
      Tyk-2 and Jak-1 kinases nor on the activation of Stat-1, Stat-2, and Stat-3.
      Taken all together, these data establish that the PI 3'-kinase serine kinase is
      activated by IFN-alpha and may play an important role in the transmission of type
      I IFN receptor-generated signals.

PMID- 9036990
TI  - Enhancement of TNF receptor p60-mediated cytotoxicity by TNF receptor p80:
      requirement of the TNF receptor-associated factor-2 binding site.
AB  - TNFR p60 (TNFR60) is the main mediator of TNF-induced apoptosis, although in some
      cells TNFR80 is also involved. TNFR80-dependent induction or enhancement of
      cytotoxicity has been explained by intracellular signaling, "ligand passing," or
      induction of endogenous TNF. Using HeLa transfectants expressing wild-type TNFR80
      and deletion mutants derived from them, we have investigated the mechanism of
      TNFR80-mediated cytotoxicity. TNFR80 induces no cytotoxicity on its own, but is
      functional in these transfectants, as selective stimulation activates nuclear
      factor-kappaB (NF-kappaB) and induces NF-kappaB-dependent cellular responses (IL
      6 and manganese superoxide dismutase). TNFR60-induced cytotoxicity, however, is
      enhanced about 1000-fold by costimulation of TNFR80, whereas only additive
      responses are observed with regard to NF-kappaB-dependent responses. Ligand
      passing is not critically involved, because a similar potentiation of TNFR60
      mediated cytotoxicity was observed when agonistic Abs were used for stimulation
      of both receptors. In addition, in HeLa cells overexpressing a truncated form of
      TNFR80 lacking the cytoplasmic domain, no TNFR80-dependent potentiation of TNFR60
      mediated cytotoxicity was detectable, emphasizing that intracellular signaling of
      TNFR80 is required for synergistic activity. The involvement of endogenously
      produced TNF can be ruled out by the use of TNF-neutralizing Abs. The ability of
      TNFR80 to cooperate with TNFR60 could be mapped to the binding site for the TNF
      receptor-associated factor-2. These results are in agreement with a differential
      cooperation of both TNFR; an additive effect is obtained in those responses that
      are initiated by both receptors via identical pathways, i.e., activation of NF
      kappaB, whereas induction of cytotoxicity is most likely mediated by distinct
      signaling pathways, allowing positive cooperativity.

PMID- 9036991
TI  - Combined diesel exhaust particulate and ragweed allergen challenge markedly
      enhances human in vivo nasal ragweed-specific IgE and skews cytokine production
      to a T helper cell 2-type pattern.
AB  - We have previously shown that in vivo nasal challenge with diesel exhaust
      particles (DEP) induces both quantitative and qualitative changes in local IgE
      production and stimulates generalized local cytokine production. We have now
      investigated the combined effects of intranasal challenge with DEP plus ragweed
      allergen on local humoral immune responses. We collected nasal lavages from
      ragweed sensitized subjects at different times after nasal challenge. As compared
      with challenge with ragweed alone, challenge with both DEP and ragweed induced
      markedly higher ragweed-specific IgE but not total IgE levels or IgE-secreting
      cell numbers. Total and specific IgG4 levels also were enhanced, while total IgG
      levels were not. Synergy was also observed between the DEP and ragweed in
      altering the profile of epsilon mRNAs generated by alternative splicing, mRNAs
      that code for different expressed IgE proteins. Intranasal challenge with ragweed
      alone induced inconsistent and low levels of mucosal cytokine mRNAs. In contrast,
      challenge with both ragweed plus DEP resulted in decreased expression for Th1
      type cytokines (IFN-gamma and IL-2) but elevated expression of mRNA for other
      cytokines (IL-4, -5, IL-6, IL-10, IL-13). This synergy between DEP and natural
      allergen exposure is suggested as a key feature in increasing allergen-induced
      respiratory allergic disease.

PMID- 9036992
TI  - IL-4 expression at the onset of islet inflammation predicts nondestructive
      insulitis in nonobese diabetic mice.
AB  - In nonobese diabetic mice, autoimmune diabetes progresses in an age-linked and
      gender-dependent manner. Insulitis begins in male and female mice at
      approximately 1 mo of age; however, 70 to 90% of females, but only 10 to 20% of
      males, become diabetic by 6 mo. Multiple studies propose that proinflammatory Th1
      and immunomodulatory Th2 cytokines impact diabetes pathogenesis, but the role of
      these cytokines in spontaneous diabetes progression is not yet clear. We used
      quantitative reverse-transcriptase-coupled PCR to analyze expression of cytokines
      and APC costimulatory molecules in the islets of 20- to 180-day-old male and
      female nonobese diabetic littermates, and identified three stages in diabetes
      progression. At 1 to 2 mo of age, islet-infiltrating T cells displayed a Th1
      cytokine bias in females, and a Th2 cytokine bias in males. In females, stage II
      (2-3 mo of age) was characterized by an increase in islet-infiltrating T cells,
      APC, and Th1 cytokines, whereas male infiltrates did not increase in size, and
      Th1 cytokine expression continued to decline during this interval. Islet
      infiltration reached a plateau (stage III) in 3- to 4-mo-old females, months
      before overt diabetes onset. Our data imply that Th cytokine expression in early
      insulitis exerts substantial impact on beta cell destruction and overt diabetes.
      A clinical implication of our results is that young individuals in the early
      stages of insulitis are ideal candidates for therapeutic intervention to minimize
      beta cell destruction and morbidity.

PMID- 9036993
TI  - Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a
      class II MHC binding peptide:hapten conjugate.
AB  - Immune regulation of contact sensitivity to the poison ivy/oak catechol was
      studied at the level of class II MHC-restricted T cell recognition of
      hapten:peptide conjugates. In this study we have shown that 1) T cells from
      C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3
      pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized
      peptides derived from syngeneic cells linked to the same catechol; 2) T cells
      from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in
      response to a peptide carrier:PDC conjugate only when it was linked at the 7th,
      but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization
      studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity
      following treatment with a single I-Ak binding peptide carrying PDC covalently
      bound to a lysine residue at the middle (7th) TCR contact position. Tolerization
      with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell
      proliferative responses that correlated with diminished IL-2 secretion. On the
      basis of these data we propose that it may be sufficient to couple the hapten at
      a single, well-chosen position on a carrier peptide to target a relevant
      population of T cells involved in contact sensitivity.

PMID- 9036994
TI  - Patterns of hemopoietic reconstitution in nonobese diabetic mice: dichotomy of
      allogeneic resistance versus competitive advantage of disease-resistant marrow.
AB  - Complete replacement of the immune system via allogeneic bone marrow
      transplantation is sufficient to prevent diabetes in the nonobese diabetic (NOD)
      mouse model. In the present study we examined whether mixed allogeneic
      reconstitution would be sufficient to interrupt the autoimmune process with
      respect to occurrence of overt diabetes, as well as preexisting autoimmune
      insulitis. NOD mice were lethally irradiated and reconstituted with a mixture of
      NOD and B10.BR marrow. A relative resistance to allogeneic bone marrow
      engraftment was noted in NOD recipients of the mixed bone marrow inoculum,
      compared with disease-resistant controls. Moreover, unlike disease-resistant
      controls, all animals that initially repopulated as mixed donor/host chimeras
      became predominantly allogeneic by 4 mo, suggesting a competitive advantage for
      long term engraftment for disease-resistant marrow. All but one mouse in the
      group that engrafted with allogeneic marrow remained free of diabetes for the
      entire follow-up period (n = 22). Moreover, in all animals examined, virtually
      all islets were free of insulitis. In contrast, 74% of NOD mice that received
      similar conditioning and failed to engraft with donor marrow developed acute
      diabetes and intra-islet insulitis was present in all animals examined. These
      data suggest that NOD mice exhibit a relative resistance to engraftment compared
      with disease-resistant recipients. Conversely, animals that initially repopulated
      as a mixture of syngeneic and donor marrow become converted to virtually all
      donor by 4 mo. These data provide additional support that a defective stem cell
      is responsible for autoimmune diabetes in this experimental model.

PMID- 9036995
TI  - Blocking the CD28-B7 T cell costimulation pathway induces long term cardiac
      allograft acceptance in the absence of IL-4.
AB  - Blocking the CD28-B7 T lymphocyte costimulatory pathway with the recombinant
      protein CTLA4Ig induces long term allograft survival in rodents. It has been
      suggested that this results from selective activation of the Th2 immune pathway.
      To test this hypothesis, we compared vascularized cardiac allograft survival in
      wild-type (IL-4 +/+) and homozygous IL-4 gene-knockout (IL-4 -/-) mice. We report
      in this study that long term survival (>100 days) of fully allogeneic grafts can
      be induced readily in IL-4 -/- recipients treated with a short course of CTLA4Ig.
      We also demonstrate that IL-4 -/- mice are deficient in Th2-type cytokine
      expression following in vitro or in vivo allostimulation. These results suggest
      that IL-4 production and subsequent generation of a Th2-type immune response are
      not obligatory for CTLA4Ig-induced long term acceptance of vascularized
      allografts.

PMID- 9036996
TI  - Proinflammatory cytokines inhibit HIV-1(SF162) expression in acutely infected
      human brain cell cultures.
AB  - An understanding of how viral replication in glial cells responds to
      proinflammatory cytokines is important in delineating HIV-1 neuropathogenesis.
      Because no information is available in the literature regarding the regulatory
      effects of exogenous cytokines on acute HIV-1 replication in human brain cells,
      we studied the impact of cytokine treatment on viral p24 Ag expression. Based
      upon reports using mononuclear phagocytes derived from somatic sources, we
      hypothesized that TNF-alpha, IL-1 beta, and IL-6 would up-regulate the expression
      of HIV-1(SF162) (a monocytotropic strain) in purified microglial cells and in
      mixed brain cell cultures. This hypothesis was not supported. In fact, a
      contrary, unexpected result was obtained; whereas in purified microglial cultures
      TNF-alpha displayed a mild stimulatory effect on HIV-1 expression (15% increase
      in p24 Ag production compared with control cultures), surprisingly, IL-1 beta and
      IL-6 were highly suppressive (91 and 83% inhibition of HIV expression,
      respectively). In contrast to the findings in microglial cell cultures, TNF-alpha
      profoundly suppressed (84%) HIV-1 expression in mixed brain cell cultures, as did
      IL-1 beta (82%), and IL-6 was moderately suppressive (55% inhibition). In an
      attempt to identify factors responsible for the differential effects of TNF-alpha
      in the two brain cell infection models, it was found that compared with
      microglial cell cultures, TNF-alpha treatment of mixed brain cell cultures
      released significantly greater amounts of RANTES (regulated upon activation,
      normal T cell expressed and secreted) and macrophage inflammatory protein-1
      alpha, beta-chemokines that have been suggested to have anti-HIV-1 effects. Thus,
      these data suggest that proinflammatory cytokines possess anti-HIV-1 activity in
      the central nervous system.

PMID- 9036997
TI  - Monocytes express Fas ligand upon CD4 cross-linking and induce CD4+ T cells
      apoptosis: a possible mechanism of bystander cell death in HIV infection.
AB  - Recent evidence indicates that death of uninfected lymphocytes by apoptosis plays
      an important role in the immunopathogenesis of HIV infection. We have previously
      demonstrated that CD4 cross-linking (CD4XL) performed in PBMC results in
      induction of T cell apoptosis in an accessory cell-dependent manner. In this
      study, we have investigated the roles of Fas interaction with its ligand (FasL)
      and of accessory cells in the CD4XL model of T cell apoptosis mediated by the
      anti-CD4 mAb Leu3a- or HIV-1 envelope protein g120. Here, we provide evidence
      that CD4XL-induced CD4+ T cell apoptosis is Fas-FasL interaction dependent and
      that monocytes play a critical role in inducing T cell apoptosis. We show that
      CD4XL-induced T cell apoptosis is blocked by the addition of soluble Fas or by
      anti-FasL mAb NOK-1; depletion of monocytes from PBMC, but not of CD19+ cells or
      CD8+ cells, abrogates CD4XL-induced T cell apoptosis. Conversely, addition of
      monocytes to purified CD4+ T cells augments CD4XL-induced apoptosis. In purified
      monocytes, CD4XL results in FasL expression; in purified CD4+ T cells, however,
      CD4XL upregulates Fas but not FasL expression. These findings underscore the
      important role of monocytes in HIV disease pathogenesis and firmly support the
      notion of CD4XL as a potent mechanism for inducing bystander cell death.

PMID- 9036998
TI  - alpha beta T cell regulation and CD40 ligand dependence in murine systemic
      autoimmunity.
AB  - To explore the mechanisms by which alpha beta T cells and gamma delta T cells
      regulate systemic autoimmunity, lupus-prone mice were rendered deficient in CD40
      ligand and/or alpha beta T cells by intercrossing CD40L -/- and TCR-alpha -/-
      knockouts, generating CD40L-intact or -deficient (CD40L+ or CD40L-), alpha beta T
      cell-intact or -deficient (alpha beta+ or alpha beta-) MRL-lpr/lpr animals. As
      expected, CD40L+ alpha beta+ mice developed high titer autoantibodies along with
      severe renal and cutaneous disease. CD40L+ alpha beta- animals developed lower
      levels of autoantibodies, accompanied by less severe or delayed renal and
      cutaneous disease. CD40L- alpha beta+ mice developed even lower titers of
      autoantibodies and less severe renal disease yet developed cutaneous lesions
      indistinguishable from those of CD40L+ alpha beta+ disease. Most surprisingly,
      CD40L- alpha beta- animals developed higher levels of some autoantibodies than
      did CD40L- alpha beta+ mice and developed renal disease similar in severity to
      CD40L+ alpha beta- counterparts; however, they failed to develop skin disease.
      Thus, disruption of CD40L and alpha beta T cells provides a novel dissection of
      the physiology and pathology of murine lupus; while these data confirm previous
      findings demonstrating a role for CD40L-dependent, alpha beta T cell-dependent
      mechanisms in autoantibody production and renal disease in murine lupus, they
      also: 1) establish that alpha beta T cells may drive autoimmune skin disease by a
      CD40L-independent mechanism; 2) identify a role for CD40L in non-alpha beta T
      cell-dependent autoantibody production and autoimmune skin disease; and 3)
      suggest a role for alpha beta T cells in the down-regulation of autoimmunity
      driven by other T cells. Thus, both alpha beta and non-alpha beta T cells, such
      as gamma delta T cells, regulate systemic autoimmunity by CD40L-dependent and 
      independent mechanisms.

PMID- 9036999
TI  - Modulation of the immune response in multiple sclerosis: production of monoclonal
      antibodies specific to HLA/myelin basic protein.
AB  - Monoclonal Abs to the complex formed between human MHC class II molecules (DR7
      and DRw11) and myelin basic protein (MBP) were produced. The specificity of these
      Abs was established by both FACS analysis and complement-mediated cytotoxicity of
      MBP- or OVA-pulsed human APC of the same or of different DR restriction. These
      Abs bound to and lysed only MBP-pulsed human APC of the same DR restriction (DR7
      or DRw11) but not to APC of different DR restriction or pulsed with a different
      Ag (OVA). The physiologic role of these Abs was further investigated. They
      blocked the in vitro proliferative response to MBP-specific T cell clones
      isolated from multiple sclerosis patients in an antigen-specific and DR
      restricted manner. However, the Abs did not affect the response of MBP-specific T
      cell clones of other DR restriction nor did they interfere with the response to
      other Ags (purified protein derivative or copolymer 1) presented on APC with the
      same DR restriction. These Abs may be useful for treating multiple sclerosis in
      which reactivity to MBP is implicated. Moreover, this approach may be extended to
      other autoantigens and their counterpart autoimmune diseases.

PMID- 9037001
TI  - Eosinophils are not required for the rejection of neovascularized fetal pig
      proislet xenografts in mice.
AB  - The rejection of neovascularized pig proislet (islet precursor) xenografts in
      mice is a CD4 T cell-dependent process involving invasion of the graft site
      mainly by host CD4 T cells and eosinophils. We previously identified CD4 T cell
      dependent enhancement of intragraft IL-3, IL-4, and IL-5 mRNA expression during
      acute xeno-rejection in CBA/H recipient mice. In the present study we
      investigated the role of each cytokine and the involvement of eosinophils in the
      rejection of pig proislet xenografts using cytokine gene knockout mice (IL-4 -/-
      and IL-5 -/-) and the treatment of transplant recipients with anti-IL-3 mAb. In
      IL-4 -/- mice, IL-5 -/- recipient animals, and anti-IL-3 mAb-treated CBA/H mice,
      eosinophil accumulation at the transplant site was inhibited or ablated, but the
      kinetics of xenograft rejection was unaltered. Prolonged xenograft survival was
      only achieved in anti-CD4 mAb-treated mice and consistently correlated with the
      absence of intragraft IL-3, IL-4, and IL-5 mRNA enhancement. Together these
      findings indicate that neither IL-3, nor IL-4, nor IL-5 individually plays an
      obligatory role in the rejection process. The cytokine mRNA profile correlating
      with the lack of eosinophil recruitment was variable; the data suggest that IL-4
      regulates eosinophil involvement in the xeno-rejection reaction indirectly via
      effects on IL-5 and IL-3 transcript expression. There is also suggestive evidence
      that IL-5 may influence IL-3 and IL-4 mRNA expression via feedback inhibition.
      Eosinophils, therefore, do not play an essential role in the rejection of
      neovascularized pig proislet xenografts in mice.

PMID- 9037002
TI  - Dichotomy of blood- and skin-derived IL-4-producing allergen-specific T cells and
      restricted V beta repertoire in nickel-mediated contact dermatitis.
AB  - In this study we compared the phenotype and cytokine patterns of nickel-specific
      T cell clones (TCC) derived from blood samples and positive patch test reactions.
      A total of 252 nickel-specific TCC were established from three nonatopic patients
      with allergic contact dermatitis caused by nickel. All TCC expressed the TCR
      alpha beta, and 77% were CD4+ compared with 21% CD8+ TCC. In contrast to blood
      derived TCC, the majority of skin-derived CD4+ or CD8+ T lymphocytes produced IL
      4 either in combination with IFN-gamma (type 0 cytokine pattern) or IL-4
      exclusively (type 2 pattern). Skin-derived nickel-specific TCC of each patient
      secreted significantly more IL-4 than blood-derived TCC of the same individual.
      Analysis of TCR-V beta repertoire from two patients indicated that >40% of the
      tested TCC expressed one of the following V beta elements: V beta 13.1/13.2, V
      beta 20, V beta 2, V beta 6.7, or V beta 14. Only 20% of unstimulated T cells but
      >40% of nickel-stimulated T cells derived from peripheral blood of the same
      individuals expressed these V beta elements, suggesting a selection of certain
      TCR-V beta elements by nickel sulfate in these patients. In contrast to the
      compartmentalization of IL-4 production, there were no major differences in the
      expression of TCR-V beta elements between blood- and skin-derived nickel-specific
      TCC. These results point to a modulation of the cytokine production pattern of T
      lymphocytes after their migration from peripheral blood into the skin and a
      production of the type 2 cytokine IL-4 in acute eczematous lesions in nonatopic
      individuals.

PMID- 9037000
TI  - VHDJH gene sequences and antigen reactivity of monoclonal antibodies produced by
      human B-1 cells: evidence for somatic selection.
AB  - To understand whether the distinct VHDJH gene utilization by natural polyreactive
      Abs reflects the developmentally restricted Ig VHDJH rearrangements putatively
      expressed by B-1 cells, we generated 11 (8 IgM, 1 IgG3, 2 IgA1), 7 (6 IgM, 1
      IgG1), and 7 (2 IgM, 3 IgG1, 2 IgG3) mAb-producing lines using B-1a (surface
      CD5+, CD45RAlow), B-1b (surface CD5-, CD45RAlow, CD5 mRNA+), and B-2 (surface CD5
      , CD45RAhigh, CD5 mRNA-) cells, respectively, sorted from adult human peripheral
      blood. Most B-1a and B-1b, but no B-2, cell-derived mAbs were polyreactive; i.e.,
      they bound different self and foreign Ags with different affinities. B-1a and B-2
      mAbs preferentially utilized VH4 (p = 0.003) and VH3 (p = 0.010) genes,
      respectively. All three mAb populations utilized DXP, DLR, DN DH genes, and JH6,
      but no mAb utilized DHQ52. There were fewer unencoded nucleotide (N) additions in
      the VHDJH junctions of B-1b (3.00 +/- 2.52, mean +/- SD) than of B-1a (12.45 +/-
      3.93, p = 1.23 x 10(-5)) or B-2 (8.29 +/- 4.75, p = 0.020) mAbs. Partly due to
      the fewer N additions and a paucity of D-D fusions, the B-1b mAb CDR3s were
      significantly shorter than the B-1a mAb CDR3s (p = 0.013), which contained a
      nonrandom Tyr distribution (p = 0.003). Finally, all but two B-1 cell-derived
      mAbs were mutated, in a fashion similar to that of the Ag-selected B-2 mAbs.
      Thus, in the human adult, B-1 cells that make natural polyreactive Abs may not be
      representative of the predominantly B-1 developmental waves of colonization of
      the fetal and neonatal B cell repertoires, and are somatically selected.

PMID- 9037005
TI  - A new approach for containment of microorganisms: dual control of streptavidin
      expression by antisense RNA and the T7 transcription system.
AB  - The use of microorganisms in the open environment would be of less concern if
      they were endowed with programmed self-destruction mechanisms. Here, we propose a
      new genetic design to increase the effectiveness of cell suicide systems. It
      ensures very tight control of the derepression of cell death by the combination
      of the bacteriophage T7 RNA polymerase-lysozyme system and an inducible synthesis
      of antisense RNA and the Escherichia coli LacI repressor. Functionality of this
      regulatory concept was tested by applying it to containment of Gram-negative
      bacteria, based on the conditional expression of the lethal Streptomyces avidinii
      streptavidin gene. Toxicity of streptavidin is derived from its exceptionally
      high binding affinity for an essential prosthetic group, D-biotin. The entire
      construct was designed to allow the soil bacterium Pseudomonas putida to survive
      only in the presence of aromatic hydrocarbons and their derivatives which it can
      degrade. Under favorable growth conditions, clones escaping killing appeared at
      frequencies of only 10(-7)-10(-8) per cell per generation. The general
      requirement for biotin through the living world should make streptavidin-based
      conditional lethal designs applicable to a broad range of containment strategies.

PMID- 9037006
TI  - RNA-dependent phosphorylation of a nuclear RNA binding protein.
AB  - The human C1 heterogeneous nuclear ribonucleoprotein particle protein (hnRNP
      protein) undergoes a cycle of phosphorylation-dephosphorylation in HeLa cell
      nuclear extracts that modulates the binding of this protein to pre-mRNA. We now
      report that hyperphosphorylation of the C1 hnRNP protein is mediated by a kinase
      activity in nuclear extracts that is RNA-dependent. Although the basal
      phosphorylation of the C1 hnRNP protein in nuclear extracts reflects a casein
      kinase II-type activity, its RNA-dependent hyperphosphorylation appears to be
      mediated by a different kinase. This is indicated by the unresponsiveness of the
      RNA-stimulated hyperphosphorylation to casein kinase II inhibitors, and the
      distinct glycerol gradient sedimentation profiles of the basal versus RNA
      stimulated C1 hnRNP protein phosphorylation activities from nuclear extracts. RNA
      dependent phosphorylation was observed both for a histidine-tagged recombinant
      human C1 hnRNP protein added to nuclear extracts and also for the endogenous C1
      hnRNP protein. Additional results rule out protein kinase A, protein kinase C,
      calmodulin-dependent protein kinase II, and double-stranded RNA-activated protein
      kinase as the enzymes responsible for the RNA-dependent hyperphosphorylation of
      the C1 hnRNP protein. These results reveal the existence in nuclear extracts of
      an RNA-dependent protein kinase activity that hyperphosphorylates a known pre
      mRNA binding protein, and define an additional element to be integrated into the
      current picture of how nuclear proteins are regulated by phosphorylation.

PMID- 9037007
TI  - Assembly of an active enzyme by the linkage of two protein modules.
AB  - The feasibility of creating new enzyme activities from enzymes of known function
      has precedence in view of protein evolution based on the concepts of molecular
      recruitment and exon shuffling. The enzymes encoded by the Escherichia coli genes
      purU and purN, N10-formyltetrahydrofolate hydrolase and glycinamide
      ribonucleotide (GAR) transformylase, respectively, catalyze similiar yet distinct
      reactions. N10-formyltetrahydrofolate hydrolase uses water to cleave N10
      formyltetrahydrofolate into tetrahydrofolate and formate, whereas GAR
      transformylase catalyses the transfer of formyl from N10-formyltetrahydrofolate
      to GAR to yield formyl-GAR and tetrahydrofolate. The two enzymes show significant
      homology (approximately 60%) in the carboxyl-terminal region which, from the GAR
      transformylase crystal structure and labeling studies, is known to be the site of
      N10-formyltetrahydrofolate binding. Hybrid proteins were created by joining
      varying length segments of the N-terminal region of the PurN gene (GAR binding
      region) and the C-terminal (N10-formyltetrahydrofolate binding) region of PurU.
      Active PurN/PurU hybrids were then selected for by their ability to complement an
      auxotrophic E. coli strain. Hybrids able to complement the auxotrophs were
      purified to homogeneity and assayed for activity. The specific activity of two
      hybrid proteins was within 100- to 1000-fold of the native purN GAR
      transformylase validating the approach of constructing an enzyme active site from
      functional parts of others.

PMID- 9037008
TI  - Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300.
AB  - We report that interferon gamma (IFN-gamma) inhibits transcription of the
      macrophage scavenger receptor gene by antagonizing the Ras-dependent activities
      of AP-1 and cooperating ets domain transcription factors, apparently as a result
      of competition between AP-1/ets factors and activated STAT1 for limiting amounts
      of CBP and p300. Consistent with this model, STAT1 alpha interacts directly with
      CBP in cells, and microinjection of anti-CBP and anti-p300 antibodies blocks
      transcriptional responses to IFN-gamma. Cells lacking STAT1 fail to inhibit AP
      1/ets activity, and overexpression of CBP both potentiates IFN-gamma-dependent
      transcription and relieves AP-1/ets repression. Thus, CBP and p300 integrate both
      positive and negative effects of IFN-gamma on gene expression by serving as
      essential coactivators of STAT1 alpha, modulating gene-specific responses to
      simultaneous activation of two or more signal transduction pathways.

PMID- 9037009
TI  - Native-like structure of a protein-folding intermediate bound to the chaperonin
      GroEL.
AB  - The chaperonin GroEL binds nonnative proteins in its central channel through
      hydrophobic interactions and initiates productive folding in this space
      underneath bound co-chaperone, GroES, in the presence of ATP. The questions of
      where along the folding pathway a protein is recognized by GroEL, and how much
      structure is present in a bound substrate have remained subjects of discussion,
      with some experiments suggesting that bound forms are fully unfolded and others
      suggesting that bound species are partially structured. Here we have studied a
      substrate protein, human dihydrofolate reductase (DHFR), observing in stopped
      flow fluorescence experiments that it can rapidly bind to GroEL at various stages
      of folding. We have also analyzed the structure of the GroEL-bound protein using
      hydrogen-deuterium exchange and NMR spectroscopy. The pattern and magnitude of
      amide proton protection indicate that the central parallel beta-sheet found in
      native DHFR is present in a moderately stable state in GroEL-bound DHFR.
      Considering that the strands are derived from distant parts of the primary
      structure, this suggests that a native-like global topology is also present. We
      conclude that significant native-like structure is present in protein-folding
      intermediates bound to GroEL.

PMID- 9037010
TI  - Kinesin-73 in the nervous system of Drosophila embryos.
AB  - Kinesin-73 cDNA was shown to encode a kinesin heavy chain protein that contains
      an N-terminal motor domain and a long central region that lacks extensive coiled
      coils. The amino acid sequence of the motor domain of kinesin-73 protein is most
      closely related to the motor domains of Caenorhabditis elegans unc-104 and mouse
      KIF1A. The central region of kinesin-73 protein also is related to unc-104 and
      KIF1A, but the homology is lower than that of the motor domain. The C-terminal
      region of kinesin-73 protein contains a cytoskeleton associated protein Gly-rich
      domain, which is a putative microtubule binding site that is present in some
      cytoskeleton or dynein-associated proteins. Kinesin-73 mRNA was shown by in situ
      hybridization to be maternally expressed and widely distributed in the syncytial
      blastoderm embryo. However, later in Drosophila embryo development, expression of
      the kinesin-73 gene becomes restricted mostly to the central and peripheral
      nervous systems.

PMID- 9037011
TI  - p21-activated kinase has substrate specificity similar to Acanthamoeba myosin I
      heavy chain kinase and activates Acanthamoeba myosin I.
AB  - Acanthamoeba class I myosins are unconventional, single-headed myosins that
      express actin-activated Mg2+-ATPase and in vitro motility activities only when a
      single serine or threonine in the heavy chain is phosphorylated by myosin I heavy
      chain kinase (MIHCK). Some other, but not most, class I myosins have the same
      consensus phosphorylation site sequence, and the two known class VI myosins have
      a phosphorylatable residue in the homologous position, where most myosins have an
      aspartate or glutamate residue. Recently, we found that the catalytic domain of
      Acanthamoeba MIHCK has extensive sequence similarity to the p21-activated kinase
      (PAK)/STE20 family of kinases from mammals and yeast, which are activated by
      small GTP-binding proteins. The physiological substrates of the PAK/STE20 kinases
      are not well characterized. In this paper we show that PAK1 has similar substrate
      specificity as MIHCK when assayed against synthetic substrates and that PAK1
      phosphorylates the heavy chain (1 mol of P(i) per mol) and activates Acanthamoeba
      myosin I as MIHCK does. These results, together with the known involvement of
      Acanthamoeba myosin I, yeast myosin I, STE20, PAK, and small GTP-binding proteins
      in membrane- and cytoskeleton-associated morphogenetic transformations and
      activities, suggest that myosins may be physiological substrates for the
      PAK/STE20 family and thus mediators of these events.

PMID- 9037012
TI  - Catalysis of protein folding by symmetric chaperone complexes.
AB  - The GroE chaperones of Escherichia coli assist protein folding under
      physiological and heat shock conditions in an ATP-dependent way. Although a
      number of details of assisted folding have been elucidated, the molecular
      mechanism of the GroE cycle remains unresolved. Here we present an experimental
      system that allows the direct analysis of the GroE-mediated folding cycle under
      stringent conditions. We demonstrate that the GroE proteins efficiently catalyze
      the folding of kinetically trapped folding intermediates of a mutant of maltose
      binding protein (MBP Y283D) in an ATP-dependent way. GroES plays a key role in
      this reaction cycle, accelerating the folding of the substrate protein MBP Y283D
      up to 50-fold. Interestingly, catalysis of the folding reaction requires the
      formation of symmetrical football-shaped GroEL x GroES2 particles and the
      intermediate release of the nonnative protein from the chaperone complex. Our
      results show that, in the presence of GroES, the complex architecture of the
      GroEL toroids allows maintenance of two highly interregulated rings
      simultaneously active in protein folding.

PMID- 9037013
TI  - Characterization of two scleroderma autoimmune antigens that copurify with human
      ribonuclease P.
AB  - Human RNase P has been purified more than 2000-fold from HeLa cells. In addition
      to the RNA component, H1 RNA, polypeptides of molecular masses 14, 20, 25, 30,
      38, and 40 kDa copurify with the enzyme activity. Sera from two different
      patients with the autoimmune disease scleroderma were used to immunodeplete human
      RNase P activity. These same sera cross-reacted on immunoblots with two of the
      copurifying polypeptides, p30 and p38, whereas an autoimmune serum that does not
      immunodeplete RNase P activity did not react with these proteins. Peptide
      fragments derived from purified p30 and p38 facilitated the molecular cloning and
      sequencing of cDNAs coding for these two polypeptides, which are now designated
      as Rpp30 and Rpp38, respectively. RPP38 cDNA encodes a polypeptide that may be
      identical to a previously identified antigen of approximately 40 kDa, which is
      immunoprecipitated by Th and To autoimmune antisera, and that has been implicated
      as a protein subunit of human RNase P by virtue of its ability to bind to H1 RNA
      in vitro. The second autoimmune antigen, Rpp30, as such, has not been described
      previously.

PMID- 9037014
TI  - The effect of macromolecular crowding on chaperonin-mediated protein folding.
AB  - The cylindrical chaperonin GroEL and its cofactor GroES mediate ATP-dependent
      protein folding in Escherichia coli. Recent studies in vitro demonstrated that
      GroES binding to GroEL causes the displacement of unfolded polypeptide into the
      central volume of the GroEL cavity for folding in a sequestrated environment.
      Resulting native protein leaves GroEL upon GroES release, whereas incompletely
      folded polypeptide can be recaptured for structural rearrangement followed by
      another folding trial. Additionally, each cycle of GroES binding and dissociation
      is associated with the release of nonnative polypeptide into the bulk solution.
      Here we show that this loss of substrate from GroEL is prevented when the folding
      reaction is carried out in the presence of macromolecular crowding agents, such
      as Ficoll and dextran, or in a dense cytosolic solution. Thus, the release of
      nonnative polypeptide is not an essential feature of the productive chaperonin
      mechanism. Our results argue that conditions of excluded volume, thought to
      prevail in the bacterial cytosol, increase the capacity of the chaperonin to
      retain nonnative polypeptide throughout successive reaction cycles. We propose
      that the leakiness of the chaperonin system under physiological conditions is
      adjusted such that E. coli proteins are likely to complete folding without
      partitioning between different GroEL complexes. Polypeptides that are unable to
      fold on GroEL eventually will be transferred to other chaperones or the
      degradation machinery.

PMID- 9037015
TI  - A novel 3'-end repair mechanism in an RNA virus.
AB  - Many positive-stranded RNA viruses contain short, single-stranded 3' ends that
      are vulnerable to degradation by host cellular RNases. Therefore, the existence
      of a 3'-end repair mechanism (analogous to cellular telomerases) must be required
      and/or advantageous for RNA viruses. Accordingly, we provide evidence suggesting
      that deletions of up to 6 nt from the 3' end of satellite (sat-) RNA C (a small
      parasitic RNA associated with turnip crinkle carmovirus) are repaired to the wild
      type sequence in vivo and in vitro. The novel 3'-end repair mechanism involves
      the production of 4-8 nt oligoribonucleotides by abortive synthesis by the viral
      replicase using the 3' end of the viral genomic RNA as template. Based on our in
      vitro results, we postulate that the oligoribonucleotides are able to prime
      synthesis of wild-type negative-strand sat-RNA C in a reaction that does not
      require base pairing of the oligoribonucleotides to the mutant, positive-strand
      RNA template. The discovery of a 3'-end repair mechanism opens up new strategies
      for interfering with viral infections.

PMID- 9037016
TI  - Rapid determination of single base mismatch mutations in DNA hybrids by direct
      electric field control.
AB  - We have demonstrated that controlled electric fields can be used to regulate
      transport, concentration, hybridization, and denaturation of single- and double
      stranded oligonucleotides. Discrimination among oligonucleotide hybrids with
      widely varying binding strengths may be attained by simple adjustment of the
      electric field strength. When this approach is used, electric field denaturation
      control allows single base pair mismatch discrimination to be carried out rapidly
      (<15 sec) and with high resolution. Electric field denaturation takes place at
      temperatures well below the melting point of the hybrids, and it may constitute a
      novel mechanism of DNA denaturation.

PMID- 9037018
TI  - Purification and characterization of the prothoracicotropic hormone of Drosophila
      melanogaster.
AB  - The prothoracicotropic hormone (PTTH) of Drosophila melanogaster is a modulator
      of ecdysteroid (molting hormone) synthesis and was isolated and characterized
      from extracts of whole larvae (approximately 4 x 10(5) larvae). The purification
      protocol included delipidation, salt-extraction, heat treatment, conventional
      column chromatography, and HPLC, and yielded about 50 microg of pure hormone.
      Biological activity was followed using a ring gland in vitro assay in which
      ecdysteroidogenesis by control ring glands as measured by radioimmunoassay was
      compared with ring gland incubations containing active fractions. The molecular
      weight of the purified PTTH was 45 kDa and N-terminal amino acid sequence
      analysis indicated that those analyzed sequences displayed no significant
      homology with known peptides or peptide hormones, including PTTH from the
      silkmoth, Bombyx mori. Western blot analysis indicated that the native form of
      Drosophila PTTH was a single 66-kDa polypeptide with N-linked carbohydrate chains
      and intrachain disulfide bonds. The purified 45-kDa peptide is the deglycosylated
      form, a result of glycosidase activity present during preparation of the PTTH
      extract. The deglycosylated form shows heterogeneity, presumably as a result of
      varying degrees of deglycosylation at the N terminus.

PMID- 9037017
TI  - Antifolate-resistant mutants of Plasmodium falciparum dihydrofolate reductase.
AB  - Single and multiple mutations at residues 16, 51, 59, 108, and 164 of Plasmodium
      falciparum dihydrofolate reductase (pfDHFR) have been linked to antifolate
      resistance in malaria. We prepared and characterized all seven of the pfDHFR
      mutants found in nature, as well as six mutants not observed in nature. Mutations
      involving residues 51, 59, 108, or 164 conferred cross resistance to both the
      antifolates pyrimethamine and cycloguanil, whereas mutation of residue 16
      specifically conferred resistance to cycloguanil. The antifolate resistance of
      enzyme mutants found in nature correlated with in vivo antifolate resistance;
      however, mutants not found in nature were either poorly resistant or had
      insufficient catalytic activity to support DNA synthesis. Thus, specific
      combinations of multiple mutations at target residues were selected in nature to
      optimize resistance. Further, the resistance of multiple mutants was more than
      the sum of the component single mutations, indicating that residues were selected
      for their synergistic as well as intrinsic effects on resistance. Pathways
      inferred for the evolution of pyrimethamine-resistant mutants suggested that all
      multiple mutants emerged from stepwise selection of the single mutant, S108N.
      Thus, we propose that drugs targeted to both the wild-type pfDHFR and S108N
      mutant would have a low propensity for developing resistance, and hence could
      provide effective antimalarial agents.

PMID- 9037019
TI  - Isoform-specific interactions of Na,K-ATPase subunits are mediated via
      extracellular domains and carbohydrates.
AB  - The functional unit of the Na,K-ATPase consists of a catalytic alpha subunit
      noncovalently linked with a glycoprotein subunit, beta. Using ouabain binding
      assays and immunoprecipitation of rodent alpha/beta complexes, we show here that
      all six possible isozymes between three alpha and two beta isoforms can be formed
      in Xenopus oocytes. Two isoform-specific differences in alpha/beta interactions
      are observed: (i) alpha1/beta1 and alpha2/beta2 complexes, in contrast to
      alpha1/beta2 complexes, are stable against Triton X-100-mediated dissociation,
      and (ii) beta2 subunits must carry N-glycans to combine with alpha1 but not with
      alpha2. The interacting surfaces are mainly exposed to the extracellular side
      because coexpression of a truncated beta1 subunit comprising the ectodomain
      results in assembly with alpha1 and alpha2, but not with alpha3; the beta2
      ectodomain combines with alpha2 only. A chimera consisting of 81% and 19% of the
      alpha1 N terminus and alpha2 C terminus, respectively, behaves like alpha2 and
      coprecipitates with the beta2 ectodomain. In contrast, the reciprocal chimera
      does not coprecipitate with the beta2 ectodomain. These results provide evidence
      for a selective interaction of Na,K-ATPase alpha and beta subunits.

PMID- 9037020
TI  - Identification of an animal omega-3 fatty acid desaturase by heterologous
      expression in Arabidopsis.
AB  - In animals, fatty acid desaturases catalyze key reactions in the synthesis of
      arachidonic acid and other polyunsaturated fatty acids. A search of the
      Caenorhabditis elegans DNA databases, using the sequences of Arabidopsis genes,
      identified several putative desaturases. Here we describe the characterization of
      the first of these genes, fat-1. The predicted protein encoded by a fat-1 cDNA
      showed 32-35% identity with both FAD2 and FAD3 of Arabidopsis. When expressed in
      transgenic plants, fat-1 resulted in a 90% increase in the proportion of alpha
      linolenic acid in root lipids. Wild-type Arabidopsis incorporated omega-6 fatty
      acids (delta8,11,14-20:3 and delta5,8,11,14-20:4) into membrane lipids but did
      not desaturate them. By contrast, fat-1 transgenic plants efficiently desaturated
      both of these fatty acids to the corresponding omega-3 products. These findings
      indicate that the C. elegans fat-1 gene encodes the first animal representative
      of a class of glycerolipid desaturases that have previously been characterized in
      plants and cyanobacteria. The FAT-1 protein is an omega-3 fatty acyl desaturase
      that recognizes a range of 18- and 20-carbon omega-6 substrates.

PMID- 9037021
TI  - Sequence-specific RNA binding by an SR protein requires RS domain
      phosphorylation: creation of an SRp40-specific splicing enhancer.
AB  - We showed previously that ASF/SF2, a member of the SR protein family of splicing
      factors, can activate a splicing enhancer element composed of high-affinity
      ASF/SF2 binding sites. To determine whether other SR proteins can behave
      similarly, we selected a high-affinity RNA-binding site (B1) for the SR protein
      SRp40. Strikingly, the success of this selection was completely dependent on
      phosphorylation of the RS domain, as unphosphorylated SRp40 failed to select
      specific sequences. We show that three copies of B1 function as a strong splicing
      enhancer, activating an intron with suboptimal splicing signals in nuclear
      extracts. Enhancer activity in S100 extracts (which lack SR proteins) required
      SRp40 and a nuclear fraction previously found to be required for ASF/SF2
      dependent splicing. Importantly, enhancer activity was lost when SRp40 was
      replaced by ASF/SF2 or SC35, and SRp40 was the only classical SR protein found to
      be associated with the enhancer. Together, our results indicate that
      phosphorylation-dependent, sequence-specific RNA binding can impart unique
      activities to individual SR proteins.

PMID- 9037022
TI  - Cryptic single-stranded-DNA binding activities of the phage lambda P and
      Escherichia coli DnaC replication initiation proteins facilitate the transfer of
      E. coli DnaB helicase onto DNA.
AB  - The bacteriophage lambda P and Escherichia coli DnaC proteins are known to
      recruit the bacterial DnaB replicative helicase to initiator complexes assembled
      at the phage and bacterial origins, respectively. These specialized nucleoprotein
      assemblies facilitate the transfer of one or more molecules of DnaB helicase onto
      the chromosome; the transferred DnaB, in turn, promotes establishment of a
      processive replication fork apparatus. To learn more about the mechanism of the
      DnaB transfer reaction, we investigated the interaction of replication initiation
      proteins with single-stranded DNA (ssDNA). These studies indicate that both P and
      DnaC contain a cryptic ssDNA-binding activity that is mobilized when each forms a
      complex with the DnaB helicase. Concomitantly, the capacity of DnaB to bind to
      ssDNA, as judged by UV-crosslinking analysis, is suppressed upon formation of a P
      x DnaB or a DnaB x DnaC complex. This novel switch in ssDNA-binding activity
      evoked by complex formation suggests that interactions of P or DnaC with ssDNA
      may precede the transfer of DnaB onto DNA during initiation of DNA replication.
      Further, we find that the lambda O replication initiator enhances interaction of
      the P x DnaB complex with ssDNA. Partial disassembly of a ssDNA:O x P x DnaB
      complex by the DnaK/DnaJ/GrpE molecular chaperone system results in the transfer
      in cis of DnaB to the ssDNA template. On the basis of these findings, we present
      a general model for the transfer of DnaB onto ssDNA or onto chromosomal origins
      by replication initiation proteins.

PMID- 9037023
TI  - Novel pyridinium surfactants for efficient, nontoxic in vitro gene delivery.
AB  - Novel, double-chained pyridinium compounds have been developed that display
      highly efficient DNA transfection properties. The transfection efficiency of
      several of these compounds is enhanced by an order of magnitude, when compared
      with the transfection efficiency accomplished with the widely used cationic lipid
      system, lipofectin. Most importantly, the pyridinium compounds were found to be
      essentially nontoxic toward cells. Using various reporter genes, such as beta
      galactosidase and pNEO (a gene construct that renders cells resistent to
      antibiotic derivatives of neomycin like G418), we demonstrate that the enhanced
      efficiency relates to the fact that a relative higher number of cells in the
      population is transfected (approximately 50% in the case of COS cells) by the
      pyridinium derivatives, whereas the delivery of DNA per cell is also enhanced.
      Furthermore, application of the pyridinium derivatives shows little cellular
      preference in their ability to transfect cells. By systematically modifying the
      structure of the pyridinium amphiphile, i.e., by changing either the headgroup
      structure or the alkyl chains, some insight was obtained that may lead to
      unraveling the mechanism of amphiphile-mediated transfection, and thus to
      protocols that further optimize the carrier properties of the amphiphile. Our
      results reveal that unsaturated alkyl chains enhance the transfection properties
      of the pyridinium-based amphiphiles. Preliminary experiments suggest that the
      structure-dependent improvement of transfection efficiency, when comparing
      pyridinium derivatives with lipofectin, likely relates to the mechanism of
      delivery rather than the packaging of the amphiphile/DNA complex.

PMID- 9037024
TI  - In vivo control of respiration by cytochrome c oxidase in wild-type and
      mitochondrial DNA mutation-carrying human cells.
AB  - The metabolic control of respiration is still poorly understood, due mainly to
      the lack of suitable approaches for studying it in vivo. Experiments on isolated
      mammalian mitochondria have indicated that a relatively small fraction of each of
      several components of the electron transport chain is sufficient to sustain a
      normal O2 consumption rate. These experiments, however, may not reflect
      accurately the in vivo situation, due to the lack in the mitochondrial fraction
      of essential cytosolic components and to the use of excess of substrates in the
      in vitro assays. An approach is described here whereby the control of respiration
      by cytochrome c oxidase (COX; EC 1.9.3.1) was analyzed in intact cultured human
      osteosarcoma 143B.TK- cells and other wild-type cells and in mitochondrial DNA
      mutation-carrying human cell lines. Surprisingly, in wild-type cells, only a
      slightly higher COX capacity was detected than required to support the endogenous
      respiration rate, pointing to a tighter in vivo control of respiration by COX
      than generally assumed. Cell lines carrying the MERRF mitochondrial tRNA(Lys)
      gene mutation, which causes a pronounced decrease in mitochondrial protein
      synthesis and respiration rates, revealed, in comparison, a significantly greater
      COX capacity relative to the residual endogenous respiration rate, and,
      correspondingly, a higher COX inhibition threshold above which the overall
      respiratory flux was affected. The observed relationship between COX respiratory
      threshold and relative COX capacity and the potential extension of the present
      analysis to other respiratory complexes have significant general implications for
      understanding the pathogenetic role of mutations in mtDNA-linked diseases and the
      tissue specificity of the mutation-associated phenotype.

PMID- 9037026
TI  - A single zinc finger motif in the silencing factor REST represses the neural
      specific type II sodium channel promoter.
AB  - The type II voltage-dependent sodium channel is present in neuronal cells, where
      it mediates the propagation of nerve impulses. Restricted expression of the type
      II sodium channel gene to neurons is due, at least in part, to binding of the
      repressor protein REST (also termed NRSF or XBR) to the RE1 (also called NRSE)
      sequence in the type II sodium channel gene. Previous studies have shown that a
      domain in REST containing eight GL1-Kruppel zinc finger motifs mediates DNA
      binding. Deletional and GAL4-fusion gene analyses now reveal repressor domains
      that lie outside of the DNA-binding domain in both the amino and carboxyl termini
      of REST. Mutational analysis further identifies a single zinc finger motif in the
      carboxyl-terminal domain as being essential for repressing type II sodium channel
      reporter genes. These studies reveal two domains in REST that may mediate
      interactions with other proteins involved in restricting expression of a large
      set of genes to the vertebrate nervous system.

PMID- 9037025
TI  - Death effector domain-containing herpesvirus and poxvirus proteins inhibit both
      Fas- and TNFR1-induced apoptosis.
AB  - To identify novel antiapoptotic proteins encoded by DNA viruses, we searched
      viral genomes for proteins that might interfere with Fas and TNFR1 apoptotic
      signaling pathways. We report here that equine herpesvirus type 2 E8 protein and
      molluscum contagiosum virus MC159 protein both show sequence similarity to the
      death effector domains (DEDs) of the Fas/TNFR1 signaling components FADD and
      caspase-8. Yeast two-hybrid analysis revealed that E8 protein interacted with the
      caspase-8 prodomain whereas MC159 protein interacted with FADD. Furthermore,
      expression of either E8 protein or MC159 protein protected cells from Fas- and
      TNFR1-induced apoptosis indicating that certain herpesviruses and poxviruses use
      DED-mediated interactions to interfere with apoptotic signaling pathways. These
      findings identify a novel control point exploited by viruses to regulate Fas- and
      TNFR1-mediated apoptosis.

PMID- 9037028
TI  - Cloning and sequence analysis of a Bothrops jararaca cDNA encoding a precursor of
      seven bradykinin-potentiating peptides and a C-type natriuretic peptide.
AB  - A 1.8-kb cDNA clone was isolated from a Bothrops jararaca venom gland cDNA
      library that encodes a 256-aa precursor for bradykinin-potentiating peptides
      (angiotensin-converting enzyme inhibitors) and a C-type natriuretic peptide
      (CNP). The seven bradykinin-potentiating peptides are aligned tandemly after the
      hydrophobic signal peptide sequence, followed by a putative intervening sequence
      and a CNP at the C terminus. Northern blot analysis indicated the predominant
      expression of a 1.8-kb mRNA in the venom glands as well as in the spleen and the
      brain. Two lower intensity mRNA bands of 3.5 kb and 5.7 kb also hybridized to the
      cDNA clone. Radioimmunoassay for the CNP was performed using the antiserum
      against rat CNP. The presence of CNP immunoreactivity was detected in the low
      molecular weight fraction of the Bothrops jararaca venom.

PMID- 9037027
TI  - Nucleosome packaging and nucleosome positioning of genomic DNA.
AB  - The goals of this study were to assess the extent to which bulk genomic DNA
      sequences contribute to their own packaging in nucleosomes and to reveal the
      relationship between nucleosome packaging and positioning. Using a competitive
      nucleosome reconstitution assay, we found that at least 95% of bulk DNA sequences
      have an affinity for histone octamer in nucleosomes that is similar to that of
      randomly synthesized DNA; they contribute little to their own packaging at the
      level of individual nucleosomes. An equation was developed that relates the
      measured free energy to the fractional occupancy of specific nucleosome
      positions. Evidently, the bulk of eukaryotic genomic DNA is also not evolved or
      constrained for significant sequence-directed nucleosome positioning at the level
      of individual nucleosomes. Implications for gene regulation in vivo are
      discussed.

PMID- 9037029
TI  - An endogenous calcium oscillator may control early embryonic division.
AB  - Transient elevations in the concentration of free cytosolic calcium ion ([Ca2+]i)
      promote cell phase transitions in early embryonic division and persist even if
      these transitions are blocked. These observations suggest that a [Ca2+]i
      oscillator is an essential timing element of the early embryonic "master clock."
      We explore this possibility by coupling a [Ca2+]i oscillator model to an early
      embryonic cell cycle model based on the protein interactions that govern the
      activity of the M-phase-promoting factor (MPF). We hypothesize three dynamical
      states of the MPF system and choose parameter sets to represent each. We then
      investigate how [Ca2+]i dynamics may control early embryonic division in both sea
      urchin and Xenopus embryos. To investigate both systems, distinct [Ca2+]i
      profiles matching those observed in sea urchin embryos (in which [Ca2+]i exhibits
      sharp transients) and Xenopus embryos (in which [Ca2+]i is elevated and
      oscillates sinusoidally) are imposed on each of the hypothesized dynamical states
      of MPF. In the first hypothesis, [Ca2+]i oscillations entrain the autonomous MPF
      oscillator. In the second and third hypotheses, where the MPF system rests in
      excitatory and bistable states, respectively, [Ca2+]i oscillations drive MPF
      activation cycles. Simulation results show that hypotheses two and three, in
      which a [Ca2+]i oscillator is a fundamental timing element of the master clock,
      best account for key experimental observations and the questions that they raise.
      Finally, we propose experiments to elucidate further [Ca2+]i regulation and the
      fundamental components of the early embryonic master clock.

PMID- 9037030
TI  - Hepatitis C virus core protein shows a cytoplasmic localization and associates to
      cellular lipid storage droplets.
AB  - There is now abundant evidence to substantiate an important role of hepatitis C
      virus (HCV) core protein in cellular gene expression as well as in the viral
      cycle. Thus the subcellular localization of this protein has important
      implications. However, several studies have shown controversial results: the HCV
      core has been, indeed, described as cytoplasmic or nuclear depending on the size
      of the protein or on the genotype analyzed. We have studied the localization of
      the HCV core protein in two different cell lines, one nonhepatic (CHO) and the
      other hepatic (HepG2). Double immunofluorescence staining using a nuclear
      membrane marker and confocal analysis showed the core protein pattern to be
      cytoplasmic and globular. This pattern is not cell cycle-regulated. Electron
      microscopy analysis revealed the nature of the globular staining observed in
      immunofluorescence. The HCV core protein accumulated at the surface of lipid
      droplets that were also the unique morphological feature of nonhepatic core
      transfected cells. The lipid droplets were isolated by sequential
      ultracentrifugation on the basis of their density; biochemical analysis revealed
      a prevalence of triglycerides. In addition the core protein colocalized with
      apolipoprotein AII at the surface of the lipid droplets as revealed by confocal
      microscopy. Moreover analysis of liver biopsies from chronically HCV-infected
      chimpanzees revealed that HCV core is cytoplasmic and localized on the
      endoplasmic reticulum and on lipid droplets. These results clearly define the
      subcellular localization of the HCV core protein and suggest a relationship
      between the expression of the HCV core protein and cellular lipid metabolism.

PMID- 9037031
TI  - The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by
      interfering with p53 tumor suppressor function.
AB  - We have recently shown that the adenovirus type 5 E4orf6 protein interacts with
      the cellular tumor suppressor protein p53 and blocks p53 transcriptional
      functions. Here we report that the E4orf6 protein can promote focus formation of
      primary rodent epithelial cells in cooperation with adenovirus E1A and E1A plus
      E1B proteins. The E4orf6 protein can also inhibit p53-mediated suppression of E1A
      plus E1B-19kDa-induced focus formation. Mutant analysis of the E4orf6 protein
      demonstrates that these activities correlate with the ability of the adenovirus
      protein to relieve transcriptional repression mediated by the carboxyl-terminal
      region of p53 in transient transfection assays. We further demonstrate that
      expression of wild-type E4orf6 correlates with a dramatic reduction of p53 steady
      state levels in transformed rat cells. Our data demonstrate that adenovirus type
      5 encodes two different proteins, E1B-55kDa and E4orf6, that bind to p53 and
      contribute to transformation by modulating p53 transcriptional functions.

PMID- 9037032
TI  - The proliferation potential protein-related (P2P-R) gene with domains encoding
      heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows
      repressed expression during terminal differentiation.
AB  - Terminal differentiation is associated with repression in the expression of the
      proliferation potential proteins (P2P) subset of heterogeneous nuclear
      ribonucleoprotein (hnRNP) proteins. We report here the cloning and
      characterization of a 5173-bp P2P-related (P2P-R) cDNA that contains a 4214-bp
      open reading frame. Probes to this cDNA detect a single 8-kb mRNA in multiple
      murine tissues and in proliferating 3T3T cells, but not in terminally
      differentiated 3T3T adipocytes. Evidence that this cDNA can encode peptides with
      domains for hnRNP association was established by showing that such peptides are
      recognized by two monoclonal antibodies known to detect core hnRNP proteins, and
      by showing that the C130 monoclonal antibody, produced against a cDNA-derived
      fusion protein, also selectively detects native P2P hnRNP proteins. In addition,
      P2P-R cDNA-derived fusion proteins bind single-stranded nucleic acids, and a P2P
      R cDNA-derived antisense oligonucleotide selectively represses P2P expression.
      Because terminal differentiation is associated with modulation in Rb1 function,
      we assayed if products of this cDNA might interact with Rb1. Evidence that the
      P2P-R cDNA encodes a protein domain that binds Rb1 was established using a
      glutathione S-transferase fusion protein to selectively precipitate Rb1 from
      cellular extracts. Data also show that this binding is reduced by competition
      with the adenovirus E1a protein, indicating that binding occurs through the
      "pocket" domain of Rb1. These results establish that the P2P-R cDNA encodes
      protein domains involved in both hnRNP association and Rb1 binding and complement
      recent reports that localize Rb1 to sites of RNA processing in the nucleus.

PMID- 9037033
TI  - A system for mutation measurement in mammalian cells: application to gamma
      irradiation.
AB  - Monitoring of mutagenesis by environmental agents for the purpose of preventing
      genetic disease including cancer must include quantitation of cell killing,
      sensitive measurement of mutation production by appropriate doses of each agent,
      and assessment of mutation repair effects in mammalian cells. A four-step
      procedure, in the presence and absence of a repair suppressor, is proposed: (i)
      determination of the survival curve; (ii) measurement of the mitotic index in
      cells collected after treatment with colcemid; (iii) construction of a
      mutagenesis yield curve in the presence and absence of a repair suppressor, like
      caffeine; and (iv) assessment of the effect of test agents on the repair of
      mutations produced by other mutagens. The procedure is quantitative,
      reproducible, and reasonably rapid. It involves measurement of mutations causing
      visible chromosomal aberrations. Numerical parameters are proposed defining
      quantitatively mutation, cell killing, and mutation repair capacity. The
      procedure is applied to gamma-irradiation and can detect the effects of doses as
      low as 2-5 cGy. Theoretical analysis of the underlying processes is presented,
      using the concept of D(0)E, the effective dose of mutagen after repair mechanisms
      and neutralizing agents have acted. Microscopically visible chromosome
      aberrations are due to mutations that distort the process of mitotic chromosome
      condensation, with or without actual chromosome breakage.

PMID- 9037034
TI  - Microtubule-mediated transport of organelles and localization of beta-catenin to
      the future dorsal side of Xenopus eggs.
AB  - The dorsal-ventral axis in frog embryos is specified during the first cell cycle,
      when the cortex rotates relative to the cytoplasmic core along parallel
      microtubules associated with the core. Cytoplasmic transfer experiments suggest
      that dorsal determinants are transported 90 degrees from the vegetal pole to the
      dorsal equator, even though the cortex rotates only 30 degrees. Here we show
      that, during rotation, small endogenous organelles are rapidly propelled along
      the subcortical microtubules toward the future dorsal side and that fluorescent
      carboxylated beads injected into the vegetal pole are transported at least 60
      degrees toward the equator. We also show that deuterium oxide, which broadens the
      zone of dorsalization even though it reduces the extent of rotation and is known
      to randomize the microtubules, also randomizes the direction of organelle
      transport. Moreover, beta-catenin, a component of the Wnt signaling pathway that
      possesses dorsalizing activity in Xenopus, colocalizes with subcortical
      microtubules at the dorsal side of the egg at the end of rotation. We propose
      that cortical rotation functions to align subcortical microtubules, which then
      mediate the transport of dorsal determinants toward their plus ends on one side
      of the egg.

PMID- 9037037
TI  - Systematic isolation of peptide signal molecules regulating development in hydra:
      LWamide and PW families.
AB  - To isolate new peptide signal molecules involved in regulating developmental
      processes in hydra, a novel screening project was developed. Peptides extracted
      from the tissue of Hydra magnipapillata were systematically purified to
      homogeneity using HPLC. A fraction of each purified peptide was examined by
      differential display-PCR for its ability to affect gene expression in hydra.
      Another fraction was used to determine the tentative structure using an amino
      acid sequence analyzer and/or a mass spectrometer. Based on the results, peptides
      of potential interest were selected for chemical synthesis, followed by
      confirmation of the identity of the synthetic with the native peptides using
      HPLC. Using this approach, 286 peptides have been isolated, tentative amino acid
      sequences have been determined for 95 of them, and 19 synthetic peptides
      identical to native ones were produced. The 19 synthetic peptides were active in
      a variety of biological tests. For example, Hym-54 stimulated muscle contraction
      in adult polyps of hydra and sea anemone, Anthopleura fuscoviridis, and induced
      metamorphosis of planula, the larval stage, into polyps in a marine hydrozoan
      species, Hydractinia serrata. Another peptide, Hym-33H, inhibited nerve cell
      differentiation in hydra and induced tissue contraction in planula of Hydractinia
      serrata. The evidence obtained so far suggests that hydra contains a large number
      (>350) of peptide signal molecules involved in regulating developmental or other
      processes in cnidaria. These peptides can be isolated and their functions
      examined systematically with the new approach developed in this study.

PMID- 9037036
TI  - Drosophila Myc is oncogenic in mammalian cells and plays a role in the diminutive
      phenotype.
AB  - Biochemical and biological activities of Myc oncoproteins are highly dependent
      upon their association with another basic region helix-loop-helix/leucine zipper
      (bHLH/LZ) protein, Max. Our previous observation that the DNA
      binding/dimerization region of Max is absolutely conserved throughout vertebrate
      evolution provided the basis for a yeast two-hybrid interaction screen that led
      to the isolation of the Drosophila Myc (dMyc1) protein. Structural conservation
      in regions of known functional significance is consistent with the ability of
      dMyc1 to interact with vertebrate Max, to transactivate gene expression in yeast
      cells, and to cooperate with activated H-RAS to effect the malignant
      transformation of primary mammalian cells. The ability of P-element-mediated
      ectopic expression of dmyc1 to reverse a subset of the phenotypic alterations
      associated with the diminutive mutation suggests that diminutive may correspond
      to dmyc1. This finding, along with the localization of dmyc1 expression to zones
      of high proliferative activity in the embryo, implicates dMyc1 as an integral
      regulator of Drosophila growth and development.

PMID- 9037040
TI  - Solar UVB-induced DNA damage and photoenzymatic DNA repair in antarctic
      zooplankton.
AB  - The detrimental effects of elevated intensities of mid-UV radiation (UVB), a
      result of stratospheric ozone depletion during the austral spring, on the primary
      producers of the Antarctic marine ecosystem have been well documented. Here we
      report that natural populations of Antarctic zooplankton also sustain significant
      DNA damage [measured as cyclobutane pyrimidine dimers (CPDs)] during periods of
      increased UVB flux. This is the first direct evidence that increased solar UVB
      may result in damage to marine organisms other than primary producers in
      Antarctica. The extent of DNA damage in pelagic icefish eggs correlated with
      daily incident UVB irradiance, reflecting the difference between acquisition and
      repair of CPDs. Patterns of DNA damage in fish larvae did not correlate with
      daily UVB flux, possibly due to different depth distributions and/or different
      capacities for DNA repair. Clearance of CPDs by Antarctic fish and krill was
      mediated primarily by the photoenzymatic repair system. Although repair rates
      were large for all species evaluated, they were apparently inadequate to prevent
      the transient accumulation of substantial CPD burdens. The capacity for DNA
      repair in Antarctic organisms was highest in those species whose early life
      history stages occupy the water column during periods of ozone depletion (austral
      spring) and lowest in fish species whose eggs and larvae are abundant during
      winter. Although the potential reduction in fitness of Antarctic zooplankton
      resulting from DNA damage is unknown, we suggest that increased solar UV may
      reduce recruitment and adversely affect trophic transfer of productivity by
      affecting heterotrophic species as well as primary producers.

PMID- 9037041
TI  - Evolutionary mechanisms and population dynamics of the third variable envelope
      region of HIV within single hosts.
AB  - Clonal diversifications of HIV virus were monitored by periodic samplings on each
      of the six patients with regard to 183- to 335-bp segments of the env gene, which
      invariably included the functionally critical V3 region. Subsequently, six
      individual phylogenetic trees of viral variants were constructed. It was found
      that at one time or another during the course of disease progression, viral
      variants were inexplicably released from a strong negative selection against
      nonsynonymous base substitutions, possibly indicating positive selection. This
      resulted in concentrated amino acid substitutions at five specific sites within
      the V3 region. It was noted that these sites were often involved as antigenic
      determinants that provoked the host immune response and that these sites were
      also involved in the determination of viral phenotypes as to their cell tropism,
      syncytium formation capability, and replication rates.

PMID- 9037042
TI  - Evidence that eukaryotic triosephosphate isomerase is of alpha-proteobacterial
      origin.
AB  - We have cloned and sequenced genes for triosephosphate isomerase (TPI) from the
      gamma-proteobacterium Francisella tularensis, the green non-sulfur bacterium
      Chloroflexus aurantiacus, and the alpha-proteobacterium Rhizobium etli and used
      these in phylogenetic analysis with TPI sequences from other members of the
      Bacteria, Archaea, and Eukarya. These analyses show that eukaryotic TPI genes are
      most closely related to the homologue from the alpha-proteobacterium and most
      distantly related to archaebacterial homologues. This relationship suggests that
      the TPI genes present in modern eukaryotic genomes were derived from an alpha
      proteobacterial genome (possibly that of the protomitochondrial endosymbiont)
      after the divergence of Archaea and Eukarya. Among these eukaryotic genes are
      some from deeply branching, amitochondrial eukaryotes (namely Giardia), which
      further suggests that this event took place quite early in eukaryotic evolution.

PMID- 9037043
TI  - The complete mitochondrial genome of the wallaroo (Macropus robustus) and the
      phylogenetic relationship among Monotremata, Marsupialia, and Eutheria.
AB  - The complete mitochondrial DNA (mtDNA) (16,896 nt) of the wallaroo (Macropus
      robustus) was sequenced. The concatenated amino acid sequences of 12
      mitochondrial protein-coding genes of the wallaroo plus those of a number of
      other mammals were included in a phylogenetic study of early mammalian
      divergences. The analysis joined monotremes and marsupials (the Marsupionta
      hypothesis) to the exclusion of eutherians. The analysis rejected significantly
      the commonly acknowledged Theria hypothesis, according to which Marsupialia and
      Eutheria are grouped together to the exclusion of Monotremata. The region
      harboring the gene for lysine tRNA (tRNA-Lys) in the mtDNA of other vertebrates
      is in the wallaroo occupied by a sequence (tRNA-Lys) that lacks both an anticodon
      loop as well as the anticodon for the amino acid lysine. An alternative tRNA-Lys
      gene was not identified in any other region of the mtDNA of the wallaroo,
      suggesting that a tRNA-Lys of nuclear origin is imported into marsupial
      mitochondria. Previously described RNA editing of tRNA-Asp and rearrangement of
      some tRNA genes were reconfirmed in the mtDNA of the wallaroo. The divergence
      between Monotremata/Marsupialia and Eutheria was timed to approximately 130
      million years before present (MYBP). The same calculations suggested that
      Monotremata and Marsupialia diverged approximately 115 MYBP and that Australian
      and American marsupials separated approximately 75 MYBP. The findings also show
      that many, probably most, extant eutherian orders had their origin in middle to
      late Cretaceous times, 115-65 MYBP.

PMID- 9037044
TI  - The strength of indirect selection on female mating preferences.
AB  - An important but controversial class of hypotheses concerning the evolution of
      female preferences for extreme male mating displays involves "indirect
      selection." Even in the absence of direct fitness effects, preference for males
      with high overall fitness can spread via a genetic correlation that develops
      between preference alleles and high fitness genotypes. Here we develop a
      quantitative expression for the force of indirect selection that (i) applies to
      any female mating behavior, (ii) is relatively insensitive to the underlying
      genetics, and (iii) is based on measurable quantities. In conjunction with the
      limited data now available, it suggests that the evolutionary force generated by
      indirect selection on preferences is weak in absolute terms. This finding raises
      the possibility that direct selection on preference genes may often be more
      important than indirect selection, but more data on the quantities identified by
      our model and on direct selection are needed to decide the question.

PMID- 9037045
TI  - Adenovirus-mediated gene transfer and expression of human beta-glucuronidase gene
      in the liver, spleen, and central nervous system in mucopolysaccharidosis type
      VII mice.
AB  - Mucopolysaccharidosis type VII (Sly syndrome) is a lysosomal storage disease
      caused by inherited deficiency of the lysosomal enzyme beta-glucuronidase. A
      murine model of this disorder has been well characterized and used to study a
      number of forms of experimental therapies, including gene therapy. We produced
      recombinant adenovirus that expresses human beta-glucuronidase and administered
      this recombinant adenovirus to beta-glucuronidase-deficient mice intravenously.
      The beta-glucuronidase activities in liver and spleen were elevated to 40% and
      20%, respectively, of the heterozygote enzymatic level at day 16. Expression
      persisted for at least 35 days. Pathological abnormalities of these tissues were
      also improved, and the elevated levels of urinary glycosaminoglycans were reduced
      in treated mice. However, the beta-glucuronidase activity in kidney and brain was
      not significantly increased. After administration of the recombinant adenovirus
      directly into the lateral ventricles of mutant mice, the beta-glucuronidase
      activity in crude brain homogenates increased to 30% of heterozygote activity.
      Histochemical demonstration of beta-glucuronidase activity in brain revealed that
      the enzymatic activity was mainly in ependymal cells and choroid. However, in
      some regions, the adenovirus-mediated gene expression was also evident in brain
      parenchyma associated with vessels and in the meninges. These results suggest
      that adenovirus-mediated gene delivery might improve the central nervous system
      pathology of mucopolysaccharidosis in addition to correcting visceral pathology.

PMID- 9037046
TI  - Mutations in the mariner transposase: the D,D(35)E consensus sequence is
      nonfunctional.
AB  - Genetic analysis of eukaryote transposases and comparison with their prokaryote
      counterparts have been greatly hindered by difficulty in isolating mutations. We
      describe a simple eye-color screen that facilitates isolation and analysis of
      mutations in the mariner transposase in Drosophila melanogaster. Use of ethyl
      methanesulfonate and site-directed mutagenesis has identified 18 residues that
      are critical for in vivo excision of a target mariner element. When the mutations
      were examined in heterozygous mutant/nonmutant genotypes, more than half of the
      mutant transposase proteins were found to reduce the activity of the wild-type
      transposase, as assayed by the frequency of germline excision of a target
      element. Remarkably, transposase function is obliterated when the D,D(34)D
      acidic, ion-binding domain is replaced with the consensus sequence D,D(34)E found
      in the nematode Tc1 transposase and in many other transposases in the
      superfamily. A number of mutations strongly complement wild-type transposase in a
      dominant-negative manner, suggestive of subunit interactions in the excision
      reaction; these mutations are located in a small region that includes part of the
      D,D(34)D motif. Transposase function also is eliminated by a mutation in the
      inferred initiation codon and by a mutation in a putative nuclear localization
      signal.

PMID- 9037047
TI  - Triplet repeat polymorphism in the transmembrane region of the MICA gene: a
      strong association of six GCT repetitions with Behcet disease.
AB  - A member of a novel family of the human major histocompatibility complex (MHC)
      class I genes termed MIC (MHC class I chain-related genes), MICA, has been
      recently identified near the HLA-B gene on the short arm of human chromosome 6.
      The predicted amino acid sequence of the MICA chain suggests that it folds
      similarly to typical class I chains and may have the capacity to bind peptides or
      other short ligands. Therefore, MICA is predicted to have a specialized function
      in antigen presentation or T cell recognition. During nucleotide sequence
      analyses of the MICA genomic clone, we found a triplet repeat microsatellite
      polymorphism of (GCT/AGC)n in the transmembrane (TM) region of the MICA gene. In
      68 HLA homozygous B cell lines, 5 distinct alleles of this microsatellite
      sequence were detected. One of them contained an additional one base insertion
      that created a frameshift mutation resulting in a premature termination codon in
      the TM region. This particular allele may encode a soluble, secreted form of the
      MICA molecule. In addition, we have investigated this microsatellite polymorphism
      in 77 Japanese patients with Behcet disease, which is known to be associated with
      HLA-B51. The microsatellite allele consisting of 6 repetitions of GCT/AGC was
      present at significantly higher frequency in the patient group (Pc = 0.00055)
      than in a control population. Furthermore, the (GCT/AGC)6 allele was present in
      all B51 positive patients and in an additional 13 B51 negative patients. These
      results suggest the possibility of a primary association of Behcet disease with
      MICA rather than HLA-B.

PMID- 9037048
TI  - High-resolution functional mapping of a cloned gene by genetic footprinting.
AB  - We describe an efficient method for introducing and analyzing a comprehensive set
      of mutations in a cloned gene to map its functional organization. The technique,
      genetic footprinting, uses a retroviral integrase to generate a comprehensive
      library of mutants, each of which bears a single insertion of a defined
      oligonucleotide at a random position in the gene of interest. This mutant library
      is selected for gene function en masse. DNA samples are isolated from the library
      both before and after selection, and the mutations represented in each sample are
      then analyzed. The analysis is designed so that a mutation at a particular
      location gives rise to an electrophoretic band of discrete mobility. For the
      whole library, this results in a ladder of bands, each band representing a
      specific mutation. Mutants in which the inserted sequence disrupts a feature that
      is required for the selected function, ipso facto, fail the selection. The
      corresponding bands are therefore absent from the ladder of bands obtained from
      the library after selection, giving rise to a footprint representing features of
      the gene that are essential for the selected function. Because the sequence of
      the inserted oligonucleotide is known, and its position can be inferred precisely
      from the electrophoretic mobility of the corresponding band, the precise location
      and sequence of mutations that disrupt gene function can be determined without
      isolating or sequencing individual mutants. This method should be generally
      applicable for saturation mutagenesis and high-resolution functional mapping of
      cloned DNA sequences.

PMID- 9037049
TI  - Germ-line knockout heterokaryons of an essential alpha-tubulin gene enable high
      frequency gene replacement and a test of gene transfer from somatic to germ-line
      nuclei in Tetrahymena thermophila.
AB  - The haploid Tetrahymena thermophila genome contains a single alpha-tubulin (ATU)
      gene. Using biolistic transformation, we disrupted one of the two copies of the
      ATU gene in the diploid germ-line micronucleus. The heterozygous germ-line
      transformants were made homozygous in the micronucleus by mating to a star strain
      containing a defective micronucleus. This mating, known as round 1 genomic
      exclusion, resulted in two heterokaryon clones of different mating types which
      have both copies of the ATU gene knocked out in the micronucleus but only wild
      type genes in the polycopy somatic macronucleus. When these heterokaryons were
      mated, the exconjugant progeny cells did not grow because the new somatic
      macronuclei do not have any alpha-tubulin genes. However, when these conjugants
      were transformed with a functional marked ATU gene, viable transformants were
      obtained that contained the transforming ATU gene at the homologous locus in the
      new macronucleus. The exconjugant progeny could be rescued at a high efficiency
      (900 transformants per microg of DNA) with a wild-type ATU gene. Unlike previous
      macronuclear transformation protocols, this strategy should allow introduction of
      highly disadvantageous (but viable) mutations into Tetrahymena, providing a
      powerful tool for molecular and functional studies of essential genes. These
      knockout heterokaryons were used to demonstrate that gene transfer from somatic
      macronuclei to germ-line micronuclei occurs rarely if at all.

PMID- 9037050
TI  - Transcriptional regulation in Archaea: in vivo demonstration of a repressor
      binding site in a methanogen.
AB  - The status of the Archaea as one of the three primary Domains emphasizes the
      importance of understanding their molecular fundamentals. Basic transcription in
      the Archaea resembles eucaryal transcription. However, little is known about
      transcriptional regulation. We have taken an in vivo approach, using genetics to
      address transcriptional regulation in the methanogenic Archaeon Methanococcus
      maripaludis. We identified a repressor binding site that regulates nif (nitrogen
      fixation) gene expression. The repressor binding site was palindromic (an
      inverted repeat) and was located just after the transcription start site of nifH.
      Mutations that changed the sequence of the palindrome resulted in marked
      decreases in repression by ammonia, even when the palindromic nature of the site
      was retained. The same mutations greatly decreased binding to the site by
      components of cell extract. These results provide the first partial description
      of a transcriptional regulatory mechanism in the methanogenic Archaea. This work
      also illustrates the utility of genetic approaches in Methanococcus that have not
      been widely used in the methanogens: directed mutagenesis and reporter gene
      fusions with lacZ.

PMID- 9037051
TI  - A genetic system to identify DNA polymerase beta mutator mutants.
AB  - DNA polymerase beta (pol beta) is a 39-kDa protein that functions in DNA repair
      processes in mammalian cells. As a first step toward understanding mechanisms of
      polymerase fidelity, we developed a genetic method to identify mammalian pol beta
      mutator mutants. This screen takes advantage of a microbial genetics assay and
      the ability of rat pol beta to substitute for Escherichia coli DNA polymerase I
      in DNA replication in vivo. Using this screen, we identified 13 candidate pol
      beta mutator mutants. Three of the candidate mutator mutants were further
      characterized in vivo and shown to confer an increased spontaneous mutation
      frequency over that of wild-type pol beta to our bacterial strain. Purification
      and subsequent analysis of one of our putative mutator proteins, the pol beta-14
      protein, showed that it possesses intrinsic mutator activity in four different
      assays that measure the fidelity of DNA synthesis. Therefore, residue 265, which
      is altered in pol beta-14 and another of our mutant proteins, pol beta-166, is
      probably critical for accurate DNA synthesis by pol beta. Thus, our genetic
      method of screening for pol beta mutator mutants is useful in identifying active
      mammalian DNA polymerase mutants that encode enzymes that catalyze DNA synthesis
      with altered fidelity compared with the wild-type pol beta enzyme.

PMID- 9037052
TI  - Evidence for a role for DNA polymerase beta in mammalian meiosis.
AB  - DNA polymerase beta (pol beta) is an enzyme possessing both polymerase and
      deoxyribose phophatase activities. Although pol beta is not believed to
      participate in the replication of genomic DNA, several studies have indicated a
      role for pol beta in DNA repair. The high level of expression of pol beta in
      mouse and rat testes raises the possibility that pol beta participates in
      mammalian meiosis. Using antibody localization, we detect foci that stain with
      pol beta antisera at discrete sites along homologous chromosomes as they synapse
      and progress through prophase of meiosis I. These data suggest that pol beta
      participates in meiotic events associated with synapsis and recombination.

PMID- 9037053
TI  - An unusual histone H3 specific for early macronuclear development in Euplotes
      crassus.
AB  - Characterization of the histone H3 genes of the ciliated protozoan Euplotes
      crassus indicates that one gene functions only during the sexual phase of the
      life cycle. Maximum expression of this gene, as judged by transcript
      accumulation, correlates with DNA replications leading to polytenization of the
      micronuclear chromosomes before massive DNA elimination, which produces a
      transcriptionally active macronucleus. Transcripts of the other gene accumulate
      primarily during vegetative growth and in the sexual phase of the life cycle
      during replication phases not related to polytenization. Although both histone H3
      genes encode proteins that are fairly divergent in sequence at the amino
      terminus, the meiotic/polytene-specific histone H3 contains two insertions in the
      amino terminus that increase the size of the protein by 15 amino acids. Analysis
      of micrococcal nuclease digests of chromatin using hybridization probes specific
      for micronuclear vs. macronuclear sequences indicates that a change in
      nucleosomal spacing correlates with the maximal expression of the
      meiotic/polytene-specific histone H3 gene. Thus, we surmise that this unusual
      histone H3 may play a key role in targeting DNA sequences for either
      transcriptional activation and retention in the macronucleus or
      heterochromatization and elimination.

PMID- 9037054
TI  - Antigen therapy eliminates T cell inflammation by apoptosis: effective treatment
      of experimental autoimmune neuritis with recombinant myelin protein P2.
AB  - Exposure of T cells to their specific antigen normally results in proliferation,
      but in the presence of high and repeatedly administered doses of antigen, T cells
      may undergo apoptosis. Here we demonstrate that i.v. administration of as little
      as 100 microg of recombinant P2 protein twice daily completely prevents
      experimental autoimmune neuritis induced by adoptive transfer of neuritogenic P2
      specific T cells or by immunization with the neuritogenic P2-peptide-spanning
      amino acids 53-78. Antigen treatment started after disease onset markedly
      ameliorated experimental autoimmune neuritis. The mechanism of action may be
      through programmed T cell death; a profound increase of the rate of apoptosis was
      seen in inflammatory foci of peripheral nerves and in the spleen. There was no
      cytokine switch by our Th1 cells after exposure to their specific antigen, but
      increased secretion of interferon gamma and tumor necrosis factor alpha was
      demonstrated. High antigen dose therapy using recombinant, pathogen-free protein
      may prove useful for the treatment of autoimmune inflammatory disorders of the
      nervous system.

PMID- 9037055
TI  - Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in
      the absence of IgE in a mouse model of asthma.
AB  - In patients with asthma, elevations of IgE correlate both with allergic
      inflammation of the airways and with bronchial hyperreactivity (BHR). Several
      investigations, using mouse models of this disease, have indicated a central role
      for IgE in the pathogenesis of the eosinophilic inflammation as well as in the
      obstructive airway physiology of BHR. Some diagnostic studies and therapeutic
      strategies for asthma are based on the putative role of IgE in asthma
      pathogenesis. Here, we use mice with a null mutation of the C epsilon locus to
      show that bronchial inflammation and BHR in response to allergen inhalation both
      can occur in the absence of IgE. We demonstrate that the eosinophilic bronchial
      inflammation elicited in an established mouse model of hypersensitivity to
      Aspergillus fumigatus (Af) is accompanied by the asthmatic physiology of BHR.
      Wild-type and IgE-deficient mice were sensitized intranasally with Af extract.
      Both groups of animals developed bronchoalveolar lavage eosinophilia and
      pulmonary parenchymal eosinophilia. This was accompanied by increased serum
      levels of total and Af-specific IgE in the wild-type animals only. This Af
      sensitization protocol resulted in significant BHR in both wild-type mice and IgE
      deficient mice. Interestingly, unsensitized IgE-deficient mice had increased
      bronchial responsiveness compared with unsensitized wild-type controls. We
      conclude that BHR and airways inflammation can be fully expressed via IgE
      independent mechanisms. These may involve the activation of mast cells by factors
      other than IgE as well as a mucosal lymphocyte-mediated immune response to
      allergen.

PMID- 9037056
TI  - Allergic airway sensitization induces T cell activation but not airway
      hyperresponsiveness in B cell-deficient mice.
AB  - B cells play an important role in the allergic response by producing allergen
      specific Igs as well as by serving as antigen-presenting cells. We studied the
      involvement of B cells in the development of responses in a murine model of
      allergic airway sensitization. Normal and B cell-deficient (muMt-/-) B10.BR mice
      were sensitized via the airways to ovalbumin; Ig production, cytokine elaboration
      from local lymph node cells, development of airway hyperresponsiveness, and
      histological changes in the airways were evaluated. Both strains of mice had
      increased production of T helper 2-like cytokines and developed an accumulation
      of eosinophils in the bronchial tissue after airway sensitization. However, only
      wild-type mice produced allergen-specific antibodies and exhibited altered airway
      function. B cell-deficient mice reconstituted with anti-ovalbumin IgE during the
      course of sensitization developed increases in airway responsiveness. These
      results indicated that neither B cells nor IgE were necessary for the induction
      of a T helper 2-type cytokine response or eosinophil infiltration of the airways
      after allergic sensitization but that IgE was required as a second signal for the
      development of airway hyperresponsiveness in this model of airway sensitization.

PMID- 9037057
TI  - Identification of the B cell superantigen-binding site of HIV-1 gp120.
AB  - Previous studies showed that the gp120 envelope protein of HIV-1 is able to
      crosslink membrane IgM on normal human B cells and to induce their activation in
      a V(H)3 immunoglobulin gene-family-specific manner. Because this V(H) gene family
      is the largest in the human repertoire, this superantigen (SAg) property is
      thought to have deleterious consequences for the host, including a progressive
      decline of B cells with progression of the HIV-1-induced disease. Here, we have
      identified the sequence motifs on gp120 involved in SAg binding to normal Igs. We
      show that this SAg-binding activity is present in gp120s from highly divergent
      isolates of HIV-1 belonging to clades derived from various geographical origins,
      and that carbohydrate residues are not essential for its expression. The SAg
      binding site is formed by protein sequences from two regions of the gp120
      molecule. The core motif is a discontinuous epitope spanning the V4 variable
      domain and the amino-terminal region flanking the C4 constant domain. The most
      critical residues appear to be Leu395-Asp397 and Ile425-Gln427. Residues from the
      C2 constant domain (positions 252-272) also seem to play an accessory role in SAg
      binding of gp120 to normal human Igs. These findings are important in the design
      of a successful gp120-based vaccine against HIV-1.

PMID- 9037058
TI  - Highly purified CD25- resting T cells cannot be infected de novo with HIV-1.
AB  - Previous studies have demonstrated that the expression of CD25 can distinguish
      CD25- latently infected cells from CD25+ cells actively producing virus. Our
      studies were designed to characterize the nature and stability of the viral
      genome in CD25- quiescent HIV-1-infected cells and to determine whether these
      cells could be infected de novo with HIV-1. Our results show that: (i) When
      unfractionated peripheral blood mononuclear cells are first infected with HIV-1
      and the CD25- cells then isolated, the latter contain only incomplete DNA
      transcripts and no full-length DNA or 2-LTR circles. Phytohemagglutinin
      activation of these CD25- cells results in the generation of full-length viral
      DNA and p24 production. (ii) When CD25- CD4+ cells are first purified from
      peripheral blood mononuclear cells and then incubated with HIV-1, viral DNA
      cannot be detected, suggesting that these purified cells cannot be infected.
      Furthermore, CD25-adherent cells do not facilitate the infection of CD4+ CD25- T
      cells when they were present at the time of incubation with HIV-1. Taken
      together, these studies suggest either that (i) the CD25- cells containing
      incomplete DNA transcripts are derived from infected-activated CD25+ cells, which
      subsequently become CD25- or (ii) the presence of CD25+ cells is required for the
      infection of CD25- cells in vitro.

PMID- 9037059
TI  - Graft-versus-host-disease-associated lymphoid hypoplasia and B cell dysfunction
      is dependent upon donor T cell-mediated Fas-ligand function, but not perforin
      function.
AB  - Allogeneic bone marrow transplant recipients often exhibit a graft-versus-host
      disease (GVHD)-associated immune deficiency that can be prolonged and lead to
      life-threatening infections. We have examined the role of donor T cell-mediated
      cytotoxic function in the development of GVHD-associated immune deficiency. A
      major histocompatibility complex-matched model of allogeneic bone marrow
      transplantation was employed in which lethally irradiated C3H.SW mice received a
      nonlethal dose of T cells from either perforin-deficient (B6-perforin 0/0), Fas
      ligand (FasL)-defective (B6-gld), or normal (B6) allogeneic donor mice. T cell
      depleted marrow from B6-Ly-5.1 congenic donor mice was transplanted along with
      the donor T cell populations to determine the effects of donor T cell-mediated
      cytotoxicity on engraftment. Our results demonstrate that recipients of perforin
      deficient or normal allogeneic T cells exhibit profound lymphoid hypoplasia and
      severely reduced splenic proliferative responses to lipopolysaccharide in vitro.
      In contrast, GVHD-associated lymphoid hypoplasia is dramatically reduced and in
      vitro B cell function is intact in recipients of FasL-defective allogeneic T
      cells. Engraftment of myeloid and erythroid lineage cells occurs irrespective of
      donor T cell cytotoxic function. Although recipients of perforin-deficient or
      normal allogeneic T cells exhibited hematopoietic engraftment exclusively of
      donor origin, recipients of FasL-defective donor T cells exhibited significant
      mixed chimerism (Ly-5.1/Ly-5.2). Because only marrow of donor origin was
      transplanted, this finding suggests that Fas-mediated antirecipient cytotoxicity
      is required for clearance of residual hematopoietic stem cells of host origin
      that persist following lethal irradiation.

PMID- 9037060
TI  - Shuttling of initiating kinase between discrete aggregates of the high affinity
      receptor for IgE regulates the cellular response.
AB  - Using defined oligomers of IgE, our group previously studied the quantitative
      relationship between the aggregation of the high affinity receptors for IgE (Fc
      epsilonRI) and the earliest signals initiated by such aggregation: the
      phosphorylation of tyrosines on the receptor. Notably, at certain doses of the
      oligomers such phosphorylation reached a plateau level well before the
      aggregation of the receptors had reached a maximum. These findings and others led
      us to propose that aggregates of the receptor were competing for a limited amount
      of the critical kinase-thought to be Lyn in this system. This paper describes a
      test of this proposal. We incubated cells with two distinguishable IgEs and
      examined the effect of aggregating one or the other or both types on the
      phosphorylation. When receptors binding antigen-specific IgE were aggregated with
      polyvalent antigen, they became rapidly phosphorylated as expected. Remarkably,
      however, Fc epsilonRI that had already been phosphorylated by the binding of
      dimers of IgE, became dephosphorylated simultaneously. Furthermore, when the
      antigen-driven aggregates were dissociated with hapten, the phosphorylation
      pattern reverted to that seen prior to the addition of antigen: as the antigen
      driven aggregates became dephosphorylated, the receptors stably aggregated by the
      bound oligomers became rapidly rephosphorylated. Dephosphorylation of oligomer
      driven aggregates was also partially reversed during the "spontaneous"
      dephosphorylation of the antigen-driven receptors seen at longer times after
      addition of antigen. Thus signal transduction in this system is in part regulated
      by the shuttling of limited amounts of the kinase that initiates the cascade of
      phosphorylations.

PMID- 9037062
TI  - A complex major histocompatibility complex D locus variant generated by an
      unusual recombination mechanism in mice.
AB  - A spontaneous variant of the mouse class I major histocompatibility complex D(b)
      gene, designated D(bm28), is characterized. This mutation consists of a cluster
      of nucleotide substitutions in exon 3 that resembles the product of a classical
      gene conversion event in that the substituted nucleotides appear to be templated.
      However, D(bm28) is distinctive, because no single donor gene containing the
      nucleotide sequence of the mutation exists in the genome of the parent strain.
      The mutation is consistent with the expected result of an interaction of two
      donor genes at the target locus during a single recombination event. While no
      known genetic mechanism gives rise to this class of mutation, we have established
      that 10 percent of spontaneous class I mutations in the mouse major
      histocompatibility complex have this complex phenotype. This process occurs at
      the D locus and the K locus. The significance of this kind of genetic interaction
      may extend beyond the major histocompatibility complex and have importance in
      shaping other multigene families.

PMID- 9037061
TI  - In vivo accumulation of the same anti-melanoma T cell clone in two different
      metastatic sites.
AB  - In a patient with progressing metastatic melanoma, we showed that the same
      autologous tumor-cytolytic CD8+ tumor infiltrating lymphocyte (TIL) clone
      accumulated in two separate metastatic sites. This clone, which represented three
      of eight independently derived clones from a tumor deposit on the skin of the
      abdomen, also represented two of eight clones derived from a skin lesion on the
      shoulder. This clone could be identified by its use of a unique TCRBV2-nD1n-J1S6
      sequence, and could also be detected by single-stranded conformational
      polymorphism (SSCP) as the dominant TCRBV2-expressing clone among CD8+ TILs
      propagated from both shoulder and abdominal lesions. Using SSCP analysis, we also
      demonstrated that this clone was dominant in the fresh tumor tissue and in all
      TILs in which CD8+ were strongly represented, including several separate but
      parallel cultures. The SSCP pattern for this clone was not apparent among CD4+
      TILs or CD8+ peripheral blood mononuclear cells. The SSCP analysis of the tumor
      tissue prior to in vitro culture is an indication that the selection for this
      anti-tumor cytotoxic T cell clone was a reflection of its in vivo accumulation.
      Thus, we provide evidence that melanomas are immunogenic and able to select for
      cytotoxic antitumor-specific TIL clones that are expanded in vivo and can
      circulate to accumulate in different tumor sites. However, because these clones
      were isolated from progressing tumor metastases, the accumulation of these
      specific cytotoxic T cells was not sufficient to contain tumor growth.

PMID- 9037063
TI  - CD30 induction of human immunodeficiency virus gene transcription is mediated by
      TRAF2.
AB  - CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily
      expressed on activated T and B lymphocytes and natural killer cells. Ligation of
      CD30 was previously shown to induce NF-kappaB activation and HIV expression in
      chronically infected T lymphocytes. In this study, we report that two members of
      the TNFR-associated factor (TRAF) family of proteins, TRAF1 and TRAF2,
      independently bind to the intracellular domain of CD30 (CD30IC). Transient
      overexpression of TRAF2, but not TRAF1, induced NF-kappaB activation and HIV-1
      long terminal repeat-driven transcription in the T cell line, KT3. Moreover,
      dominant negative mutants consisting of the TRAF domain of TRAF1 and TRAF2
      inhibited CD30 induction of NF-kappaB activation and HIV-1 transcription. These
      results suggest that CD30 ligation may enhance the expression of HIV via TRAF-2
      mediated activation of NF-kappaB.

PMID- 9037064
TI  - Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte
      reactivities in uninfected volunteers.
AB  - A fundamental goal of current strategies to develop an efficacious vaccine for
      AIDS is the elicitation of broadly reactive cytotoxic T lymphocyte (CTL)
      reactivities capable of destroying virally infected targets. Recent application
      of recombinant canarypox ALVAC/HIV-1 vectors as vaccine immunogens in HIV-1,
      noninfected volunteers has produced CTL responses in a significant number of
      vaccinees. Using a newly developed targeting strategy, we examined the capacity
      of vaccine-induced CTL to lyse autologous targets infected with a diverse group
      of viral isolates. CTL derived from recipients of a canarypox ALVAC/HIV-1 gp160
      (MN) vaccine were found capable of lysing autologous CD4+ lymphoblasts infected
      with the prototypic LAI strain of HIV-1. When tested against autologous targets
      infected with primary HIV-1 isolates representing genetically diverse viral
      clades, CTL from ALVAC/gp160 recipients showed both a broad pattern of cytolysis
      in which viruses from all clades tested were recognized as well as a highly
      restricted pattern in which no primary isolates, including clade B, were lysed.
      Differences in the HLA haplotypes of the volunteers immunized with the envelope
      vector might be a major determinant of the relative breadth of their CTL
      response. In contrast to ALVAC/gp160 vaccinees, recipients of the ALVAC/HIV-1
      immunogen containing envelope as well as gag and protease genes consistently had
      CTL reactivities effective against a spectrum of primary isolate-infected
      targets. These studies demonstrate for the first time that clade B-based
      canarypox vaccines can elicit broad CTL reactivities capable of recognizing
      viruses belonging to genetically diverse HIV-1 clades. The results also reinforce
      the impact of viral core elements in the vaccine as well as the pattern of major
      histocompatibility complex class I allelic expression by the vaccine recipient in
      determining the relative breadth of the cellular response.

PMID- 9037065
TI  - Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase
      matrilysin.
AB  - Matrix metalloproteinases (MMPs) classically have been implicated in basement
      membrane destruction associated with late-stage tumor cell invasion and
      metastasis. However, recent studies have demonstrated that one MMP family member,
      matrilysin, is expressed in a high percentage of early-stage human colorectal
      tumors. We analyzed matrilysin expression in benign intestinal tumors from mice
      heterozygous for the ApcMin allele (Min/+) and found that the mRNA was induced in
      the majority (88%) of these adenomas. Protein was detected in the tumor cells,
      where, surprisingly, it was predominantly immunolocalized to the lumenal surface
      of dysplastic glands rather than the basement membrane or extracellular matrix.
      To address the role of matrilysin in Min intestinal tumorigenesis, we generated
      Min/+ mice deficient in this MMP by gene targeting and homologous recombination.
      The absence of matrilysin resulted in a reduction in mean tumor multiplicity in
      Min/+ animals of approximately 60% and a significant decrease in the average
      tumor diameter. Based on these findings, we conclude that matrilysin is a
      suppressor of the Min phenotype, possibly by functioning in a capacity
      independent of matrix degradation. These results argue for the use of MMP
      inhibitors in the treatment and prevention of early-stage colon cancer.

PMID- 9037066
TI  - Developmental analysis and subcellular localization of the murine homologue of
      ELL.
AB  - The ELL gene was first identified by its involvement with MLL in the
      translocation (11;19)(q23;p13.1) in acute myeloid leukemia. To date, nine other
      MLL partner genes have been cloned, but their precise functions have yet to be
      determined. To characterize the functions of ELL further, we have cloned the
      murine homologue of ELL and have found that the gene is highly conserved at the
      nucleotide and amino acid level. The open reading frame of the murine homologue
      contains 602 aa, slightly smaller than the 621 aa in the human gene. With
      Northern blot analysis, a 3.4-kb transcript is detected in all tissues examined
      with greatest levels of expression in the liver. Unlike human ELL, only a single
      transcript can be detected with either murine coding sequence or 3' untranslated
      region probes. To examine the spatial and temporal pattern of expression in
      murine development, in situ hybridization studies were performed with sense and
      antisense riboprobes from the 3' untranslated region of murine Ell. Ell is
      expressed diffusely by embryonic day 7.5 (E7.5). In addition, high levels of
      expression can be detected in maternally derived decidual tissue. At E14.5, Ell
      is expressed diffusely throughout the embryo. However by E16.5, specific
      expression in the liver and gastrointestinal tract becomes prominent and remains
      so in both neonates and adults. To determine the subcellular localization of ELL,
      we developed a polyclonal antiserum to ELL that was used for immunofluorescence
      studies in COS-7, HeLa, NIH 3T3, and A7r5 cells. The ELL protein was localized to
      the nucleus but excluded from nucleoli in all cell lines examined. Recently, the
      gene product of ELL was found to function as an RNA polymerase II elongation
      factor, an activity that is consistent with our immunofluorescence data. Thus,
      these studies extend our understanding of the normal functions of ELL and provide
      additional insight into its aberrant function when fused to MLL in acute myeloid
      leukemia.

PMID- 9037067
TI  - Recombinational construction in Escherichia coli of infectious adenoviral
      genomes.
AB  - A two-step gene replacement procedure was developed that generates infectious
      adenoviral genomes through homologous recombination in Escherichia coli. As a
      prerequisite, a human adenovirus serotype 5 (Ad5)-derived genome was first
      introduced as a PacI restriction fragment into an incP-derived replicon which, in
      contrast to ColE1-derivatives (e.g., pBR322 or pUC plasmids), is functional in a
      polA mutant of E. coli. Any modification can be introduced at will following two
      consecutive homologous recombinations between the incP/Ad5 replicon and the ColE1
      plasmid. The overall procedure requires only the in vitro engineering of the
      ColE1-derivative by flanking the desired modification with small stretches of
      identical sequences. In the first step, a cointegrate between the tetracycline
      resistant incP/Ad5 replicon and the kanamycin-resistant ColE1-derivative is
      selected by growing the polA host in the presence of both antibiotics. Resolution
      of this cointegrate is further selected in sucrose growth conditions due to the
      loss of a conditional suicide marker (the sacB gene of Bacillus subtilis) present
      in the ColE1 plasmid, leading to unmodified and modified incP/Ad5 replicons that
      can be differentiated upon restriction analysis. Consecutive rounds of this two
      step cloning procedure allowed the introduction of multiple independent
      modifications within the virus genome, with no requirement for an intermediate
      virus. The potential of this procedure is demonstrated by the recovery of several
      E1E3E4-deleted adenoviruses following transfection of the corresponding E. coli
      derived genomes in IGRP2 cells.

PMID- 9037068
TI  - Recovery of pituitary function after treatment with a targeted cytotoxic analog
      of luteinizing hormone-releasing hormone.
AB  - Recently, we developed a targeted cytotoxic analog AN-207 of luteinizing hormone
      releasing hormone (LH-RH), consisting of an intensely potent derivative of
      doxorubicin, 2-pyrrolinodoxorubicin (AN-201) conjugated to carrier agonist [D
      Lys6]LH-RH. In this study, we investigated the effects of cytotoxic analog AN
      207, designed for targeted chemotherapy and radical AN-201 on pituitary function
      in rats. A selective damage to the pituitary gonadotroph cells was found at 1
      week after a single i.v. injection of 150 nmol/kg AN-207, as evidenced by a 63%
      decrease in the LH-RH-stimulated release of LH in vitro. The release of growth
      hormone (GH) and thyrotropin (TSH), stimulated by GH-releasing hormone (GH-RH)
      and TSH-releasing hormone (TRH), respectively, was reduced by only 11-12%. In
      contrast, even a smaller dose of 75 nmol/kg of AN-201 nonselectively damaged
      pituitary function, reducing the stimulated release of LH, GH, and TSH by 57%,
      74%, and 67%, respectively. Two weeks after administration, the LH-RH-stimulated
      LH release in vivo entirely normalized in the AN-207-treated rats, and only a 13%
      decrease in the LH response was found in the group given AN-201. GH and TSH
      responses to receptor-mediated stimuli with GH-RH and TRH were normal at 2 weeks
      in both treated groups. Neither cytotoxic compound caused changes in the
      concentration of pituitary LH, GH, or TSH, as determined by RIA at 1 week and 7
      weeks after treatment. This study demonstrates that the cytotoxic LH-RH analog AN
      207 exerts highly selective effects on the gonadotroph cells containing LH-RH
      receptors and is less toxic for other cells. Conversely, its cytotoxic radical AN
      201 nonselectively damages the pituitary cells. The damaging effect of both
      cytotoxic compounds on pituitary functions is reversible. In view of its high
      selectivity and reduced toxicity, AN-207 could be a potential therapeutic agent
      for the treatment of tumors that possess receptors for LH-RH such as prostatic,
      mammary, ovarian, and endometrial cancers.

PMID- 9037069
TI  - Persistent expression of human clotting factor IX from mouse liver after
      intravenous injection of adeno-associated virus vectors.
AB  - We previously found that gene transduction by adeno-associated virus (AAV)
      vectors in cell culture can be stimulated over 100-fold by treatment of the
      target cells with agents that affect DNA metabolism, such as irradiation or
      topoisomerase inhibitors. Here we show that previous gamma-irradiation increased
      the transduction rate in mouse liver by up to 900-fold, and the topoisomerase
      inhibitor etoposide increased transduction by about 20-fold. Similar rates of
      hepatic transduction were obtained by direct injection of the liver or by
      systemic delivery via tail vein injection. Hepatocytes were much more efficiently
      transduced than other cells after systemic delivery, and up to 3% of all
      hepatocytes could be transduced after one vector injection. The presence of wild
      type AAV, which contaminates many AAV vector preparations, was required to
      observe a full response to gamma-irradiation. Injection of mice with AAV vectors
      encoding human clotting factor IX after gamma-irradiation resulted in synthesis
      of low levels of human clotting factor IX for the 5-month period of observation.
      These studies show the potential of targeted gene transduction of the liver by
      AAV vectors for treatment of various hematological or metabolic diseases.

PMID- 9037070
TI  - Zinc porphyrins: potent inhibitors of hematopoieses in animal and human bone
      marrow.
AB  - The effects of selected heme analogues on heme oxygenase activity in tissues and
      on human and rabbit bone marrow hematopoietic colony growth were examined. Zinc
      protoporphyrin (ZnPP) and zinc mesoporphyrin (ZnMP), at concentrations ranging
      between 1 and 20 microM, produced significant inhibition of human and rabbit bone
      marrow erythroid (CFU-E, BFU-E) and myeloid (CFU-GM) colony growth. The growth
      inhibition produced by ZnPP or ZnMP was not overcome with exposure of cultures to
      elevated levels of the growth factors erythropoietin and granulocyte-macrophage
      colony stimulating factor. In contrast, tin protoporphyrin and tin mesoporphyrin
      did not display any significant bone marrow toxicity when used at similar
      concentrations. In other studies, differential effects of tin mesoporphyrin and
      ZnMP administered intravenously on kidney heme oxygenase were demonstrated.
      Chromium mesoporphyrin administered intravenously proved lethal to animals. These
      results indicate that exposure of bone marrow to ZnPP and ZnMP can be deleterious
      to hematopoietic cells and raise the possibility that ZnPP, which is endogenously
      formed and found in high concentration in red blood cells in lead-poisoned
      children, may itself participate in the bone marrow toxicity produced by this
      metal.

PMID- 9037071
TI  - Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase.
AB  - Activation of the c-Abl protein tyrosine kinase by certain DNA-damaging agents
      contributes to downregulation of Cdk2 and G1 arrest by a p53-dependent mechanism.
      The present work investigates the potential role of c-Abl in apoptosis induced by
      DNA damage. Transient transfection studies with wild-type, but not kinase
      inactive, c-Abl demonstrate induction of apoptosis. Cells that stably express
      inactive c-Abl exhibit resistance to ionizing radiation-induced loss of
      clonogenic survival and apoptosis. Cells null for c-abl are also impaired in the
      apoptotic response to ionizing radiation. We further show that cells deficient in
      p53 undergo apoptosis in response to expression of c-Abl and exhibit decreases in
      radiation-induced apoptosis when expressing inactive c-Abl. These findings
      suggest that c-Abl kinase regulates DNA damage-induced apoptosis.

PMID- 9037072
TI  - Initiation of liver growth by tumor necrosis factor: deficient liver regeneration
      in mice lacking type I tumor necrosis factor receptor.
AB  - The mechanisms that initiate liver regeneration after resection of liver tissue
      are not known. To determine whether cytokines are involved in the initiation of
      liver growth, we studied the regeneration of the liver after partial hepatectomy
      (PH) in mice lacking type I tumor necrosis factor receptor (TNFR-I). DNA
      synthesis after PH was severely impaired in these animals, and the expected
      increases in the binding of the NF-kappaB and STAT3 transcription factors shortly
      after PH failed to occur. Binding of AP-1 after PH was decreased in TNFR-I
      knockout mice compared with animals with the intact receptor whereas C/EBP
      binding was not modified. Injection of interleukin 6 in TNFR-I-deficient animals
      30 min before PH corrected the defect in DNA synthesis and restored STAT3 and AP
      1 binding to normal levels but had no effect on NF-kappaB binding in the
      regenerating liver. The results indicate that TNF, signaling through the TNFR-I,
      can initiate liver regeneration and acts by activating an interleukin 6-dependent
      pathway that involves the STAT3 transcription factor.

PMID- 9037073
TI  - The Epstein-Barr virus LMP1 amino acid sequence that engages tumor necrosis
      factor receptor associated factors is critical for primary B lymphocyte growth
      transformation.
AB  - Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is essential for
      transforming primary B lymphocytes into lymphoblastoid cell lines. EBV
      recombinants with LMP1 genes truncated after the proximal 45 codons of the LMP1
      carboxyl terminus are adequate for transformation. The proximal 45 residues
      include a domain that engages the tumor necrosis factor receptor associated
      factors (TRAFs). We investigated the importance of the TRAF binding domain by
      assaying the transforming ability of recombinant EBV genomes with a deletion of
      LMP1 codons 185-211. This mutation eliminates TRAF association in yeast and in
      lymphoblasts but does not affect LMP1 stability or localization. Specifically
      mutated recombinant EBV genomes were generated by transfecting P3HR-1 cells with
      overlapping EBV cosmids. Infection of primary B lymphocytes resulted in cell
      lines that were coinfected with an LMP1 delta185-211 EBV recombinant and P3HR-1
      EBV, which has a wild-type LMP1 gene but is transformation defective due to
      another deletion. Despite the equimolar mixture of wild-type and mutated LMP1
      genes in virus preparations from five coinfected cell lines, only the wild-type
      LMP1 gene was found in 412 cell lines obtained after transformation of primary B
      lymphocytes. No transformed cell line had only the LMP1 delta185-211 gene. An EBV
      recombinant with a Flag-tagged LMP1 gene passaged in parallel segregated from the
      coinfecting P3HR-1. These data indicate that the LMP1 TRAF binding domain is
      critical for primary B lymphocyte growth transformation.

PMID- 9037074
TI  - A bacterial basic region leucine zipper histidine kinase regulating toluene
      degradation.
AB  - The two-component signal transduction pathways in bacteria use a histidine
      aspartate phosphorelay circuit to mediate cellular changes in response to
      environmental stimuli. Here we describe a novel two-component todST system, which
      activates expression of the toluene degradation (tod) pathway in Pseudomonas
      putida F1. The todS gene is predicted to encode a sensory hybrid kinase with two
      unique properties--a basic region leucine zipper dimerization motif at the N
      terminus and a duplicated histidine kinase motif. Evidence from a synthetic
      peptide model suggests that TodS binds as a dimer to a pseudopalindromic sequence
      (5'-TGACTCA), which resembles the recognition sequence of the eukaryotic
      transcription factors Fos and Jun. These results provide additional evidence that
      bacteria and eukaryotes share common regulatory motifs. The todT gene product, a
      response regulator, was overproduced as a fusion protein in Escherichia coli, and
      the purified protein was found to bind specifically to a 6-bp palindromic DNA
      structure in the tod control region. The phosphorylated form of TodT appears to
      be the activator of tod structural genes. This is the first report of a two
      component system that regulates aromatic metabolism in bacteria.

PMID- 9037075
TI  - BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related
      to degenerins and epithelial sodium channels.
AB  - The recently defined DEG/ENaC superfamily of sodium channels includes subunits of
      the amiloride-sensitive epithelial sodium channel (ENaC) of vertebrate colon,
      lung, kidney, and tongue, a molluscan FMRFamide-gated channel (FaNaC), and the
      nematode degenerins, which are suspected mechanosensory channels. We have
      identified two new members of this superfamily (BNaC1 and BNaC2) in a human brain
      cDNA library. Phylogenetic analysis indicates they are equally divergent from all
      other members of the DEG/ENaC superfamily and form a new branch or family. Human
      BNaC1 maps to 17q11.2-12 and hBNaC2 maps to 12q12. Northern blot and mouse brain
      in situ hybridizations indicate that both genes are coexpressed in most if not
      all brain neurons, although their patterns of expression vary slightly, and are
      expressed early in embryogenesis and throughout life. By analogy to the ENaCs and
      the degenerins, which form heteromultimeric channels, BNaC1 and BNaC2 may be
      subunits of the same channel.

PMID- 9037076
TI  - A binding site for Pax proteins regulates expression of the gene for the neural
      cell adhesion molecule in the embryonic spinal cord.
AB  - The neural cell adhesion molecule (N-CAM) mediates cell-cell interactions and is
      expressed in characteristic spatiotemporal patterns during development. In
      previous studies of factors that control N-CAM gene expression, we identified a
      binding site for the paired domain of Pax proteins (designated PBS) in the mouse
      N-CAM promoter. In this study, we demonstrate that a transcription factor known
      to be important for development of the central nervous system, Pax-6, binds to
      the N-CAM PBS and show that the PBS can influence N-CAM expression in vivo. Pax
      6, produced in COS-1 cells, bound to the PBS through two half-sites, PBS-1 and
      PBS-2; mutations in both of these sites completely disrupted binding. Moreover,
      nuclear extracts from embryonic day (E) 11.5 mouse embryos bound to the PBS, and
      this binding was inhibited by antibodies to Pax-6. To determine the role of the
      PBS in vivo, we generated transgenic mice with N-CAM promoter/lacZ gene
      constructs containing either a wild-type or a mutated PBS. Mutations in PBS-1 and
      PBS-2 decreased the extent of beta-galactosidase expression in the mantle layer
      of the spinal cord limiting it to ventral regions at E11.5. At E14.5, these
      mutations eliminated most of the expression that was seen in the wild-type spinal
      cord. Taken together with our previous observations that the PBS binds multiple
      Pax proteins, the data indicate that such binding contributes to the regulation
      of N-CAM gene expression during neural development.

PMID- 9037077
TI  - Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos
      expression after forepaw inflammation in infant rats.
AB  - Sweet taste and nonnutritive suckling produce analgesia to transient noxious
      stimuli in infant rats and humans. The present study evaluated the pain
      modulating effects of sucrose and suckling in a rat model of persistent pain and
      hyperalgesia that mimics the response to tissue injury in humans. Fore- and
      hindpaw withdrawal latencies from a 30 degrees or 48 degrees C brass stylus were
      determined in 10-day-old rats following paw inflammation induced by complete
      Freund's adjuvant (CFA; 1:1 injected s.c. in a 0.01 ml volume). CFA markedly
      decreased escape latencies to both 48 degrees and 30 degrees C stimulation,
      thereby demonstrating thermal hyperalgesia and mechanical allodynia. The
      combination of nonnutritive suckling and sucrose (7.5%, 0.01-0.06 ml/min)
      infusion markedly increased escape latencies to forepaw stimulation in both CFA
      treated and control rats. In contrast, intraoral sucrose and suckling did not
      increase hindpaw withdrawal latencies in either control or CFA-inflamed rats. The
      effect was specific to sweet taste because neither water nor isotonic saline
      infusion affected forepaw escape latencies. Parallel findings were obtained for
      CFA-induced Fos-like immunoreactivity (Fos-LI), a marker of neuronal activation.
      Fos-LI was selectively induced in cervical and lumbar regions ipsilateral to
      forepaw and hindpaw inflammation, respectively. Suckling-sucrose treatment
      significantly reduced Fos-LI at the cervical but not at the lumbar regions. These
      findings demonstrate: (i) the development of persistent pain and hyperalgesia in
      10-day-old rats that can be attenuated by endogenous pain-modulating systems
      activated by taste and nonnutritive suckling; (ii) the mediation of the sucrose
      suckling analgesia and antihyperalgesia at the spinal level; and (iii) a
      differential rostrocaudal maturation of descending pain-modulating systems to the
      spinal cord of 10-day-old rats. These findings may provide new clinical
      approaches for engaging endogenous analgesic mechanisms in infants following
      tissue injury and inflammation.

PMID- 9037078
TI  - Behavioral effects of estrogen receptor gene disruption in male mice.
AB  - Gonadal steroid hormones regulate sexually dimorphic development of brain
      functions and behaviors. Their nuclear receptors offer the opportunity to relate
      molecular events in neurons to simple instinctive mammalian behaviors. We have
      determined the role of estrogen receptor (ER) activation by endogenous estrogen
      in the development of male-typical behaviors by the use of transgenic estrogen
      receptor-deficient (ERKO) mice. Surprisingly, in spite of the fact that they are
      infertile, ERKO mice showed normal motivation to mount females but they achieved
      less intromissions and virtually no ejaculations. Aggressive behaviors were
      dramatically reduced and male-typical offensive attacks were rarely displayed by
      ERKO males. Moreover, ER gene disruption demasculinized open-field behaviors. In
      the brain, despite the evident loss of functional ER protein, the androgen
      dependent system appears to be normally present in ERKO mice. Together, these
      findings indicate that ER gene expression during development plays a major role
      in the organization of male-typical aggressive and emotional behaviors in
      addition to simple sexual behaviors.

PMID- 9037079
TI  - Morphological plasticity of dendritic spines in central neurons is mediated by
      activation of cAMP response element binding protein.
AB  - While evidence has accumulated in favor of cAMP-associated genomic involvement in
      long-term synaptic plasticity, the mechanisms downstream of the activated nucleus
      that underlie these changes in neuronal function remain mostly unknown. Dendritic
      spines, the locus of excitatory interaction among central neurons, are prime
      candidates for long-term synaptic modifications. We now present evidence that
      links phosphorylation of the cAMP response element binding protein (CREB) to
      formation of new spines; exposure to estradiol doubles the density of dendritic
      spines in cultured hippocampal neurons, and concomitantly causes a large increase
      in phosphorylated CREB and in CREB binding protein. Blockade of cAMP-regulated
      protein kinase A eliminates estradiol-evoked spine formation, as well as the CREB
      and CREB binding protein responses. A specific antisense oligonucleotide
      eliminates the phosphorylated CREB response to estradiol as well as the formation
      of new dendritic spines. These results indicate that CREB phosphorylation is a
      necessary step in the process leading to generation of new dendritic spines.

PMID- 9037080
TI  - Ataxia and altered dendritic calcium signaling in mice carrying a targeted null
      mutation of the calbindin D28k gene.
AB  - Intracellular calcium-binding proteins are abundantly expressed in many neuronal
      populations. Previous evidence suggests that calcium-binding proteins can
      modulate various neuronal properties, presumably by their action as calcium
      buffers. The importance of calcium-binding proteins for nervous system function
      in an intact integrated system is, however, less clear. To investigate the
      physiological role of a major endogenous calcium-binding protein, calbindin D28k
      (calbindin) in vivo, we have generated calbindin null mutant mice by gene
      targeting. Surprisingly, calbindin deficiency does not affect general parameters
      of development and behavior or the structure of the nervous system at the light
      microscopic level. Null mutants are, however, severely impaired in tests of motor
      coordination, suggesting functional deficits in cerebellar pathways. Purkinje
      neurons, the only efferent of the cerebellar cortex, and inferior olive neurons,
      the source of the climbing fiber afferent, have previously been shown to express
      calbindin. Correlated with this unusual type of ataxia, confocal calcium imaging
      of Purkinje cells in cerebellar slices revealed marked changes of synaptically
      evoked postsynaptic calcium transients. Their fast, but not their slow, decay
      component had larger amplitudes in null mutant than in wild-type mice. We
      conclude that endogenous calbindin is of crucial importance for integrated
      nervous system function.

PMID- 9037081
TI  - A post-tetanic time window for the reinforcement of long-term potentiation by
      appetitive and aversive stimuli.
AB  - Current theories on the encoding and storage of information in the brain commonly
      suppose that a short-term memory is converted into a lasting one; thus, it
      becomes consolidated over time. Within a finite period after training, such a
      short-term memory can be reinforced by behavioral and humoral stimuli. We have
      found that, long-term potentiation (LTP), a likely candidate for a memory
      encoding mechanism at the cellular level, displays similar features. LTP in the
      dentate gyrus of freely moving rats was reinforced after its induction by
      appetitive and aversive stimuli. The efficacy of these stimuli terminates about 1
      h after tetanization, which may reflect the time constants of the mechanisms
      underlying the consolidation that takes place. The reinforcement by appetitive
      and aversive stimulation was blocked by the beta-adrenergic antagonist
      propranolol, implicating norepinephrine in the underlying cellular processes.

PMID- 9037082
TI  - Progressive decline in avoidance learning paralleled by inflammatory
      neurodegeneration in transgenic mice expressing interleukin 6 in the brain.
AB  - Inflammation with expression of interleukin 6 (IL-6) in the brain occurs in many
      neurodegenerative disorders. To better understand the role of IL-6 in such
      disorders, we examined performance in a learning task in conjunction with
      molecular and cellular neuropathology in transgenic mice that express IL-6
      chronically from astrocytes in the brain. Transgenic mice exhibited dose- and age
      related deficits in avoidance learning that closely corresponded with specific
      progressive neuropathological changes. These results establish a link between the
      central nervous system expression of IL-6, inflammatory neurodegeneration, and a
      learning impairment in transgenic mice. They suggest a critical role for a
      proinflammatory cytokine in the cognitive deficits and associated
      neuroinflammatory changes that have been documented in neurodegenerative diseases
      such as Alzheimer disease and AIDS.

PMID- 9037083
TI  - Modulation by neurotransmitters of catecholamine secretion from sympathetic
      ganglion neurons detected by amperometry.
AB  - Many neuromodulators inhibit N-type Ca2+ currents via G protein-coupled pathways
      in acutely isolated superior cervical ganglion (SCG) neurons. Less is known about
      which neuromodulators affect release of norepinephrine (NE) at varicosities and
      terminals of these neurons. To address this question, we used carbon fiber
      amperometry to measure catecholamine secretion evoked by electrical stimulation
      at presumed sites of high terminal density in cultures of SCG neurons. The
      pharmacological properties of action potential-evoked NE release paralleled those
      of N-type Ca2+ channels: Release was completely blocked by Cd2+ or omega
      conotoxin GVIA, reduced 50% by 10 microM NE or 62% by 2 microM UK-14,304, an
      alpha2-adrenergic agonist, and reduced 63% by 10 microM oxotremorine M (Oxo-M), a
      muscarinic agonist. Consistent with action at M2 or M4 receptor subtypes, Oxo-M
      could be antagonized by 10 microM muscarinic antagonists methoctramine and
      tropicamide but not by pirenzepine. After overnight incubation with pertussis
      toxin, inhibition by UK-14,304 and Oxo-M was much reduced. Other neuromodulators
      known to inhibit Ca2+ channels in these cells, including adenosine, prostaglandin
      E2, somatostatin, and secretin, also depressed secretion by 34-44%. In cultures
      treated with omega-conotoxin GVIA, secretion dependent on L-type Ca2+ channels
      was evoked with long exposure to high K+ Ringer's solution. This secretion was
      not sensitive to UK-14,304 or Oxo-M. Evidently, many neuromodulators act on the
      secretory terminals of SCG neurons, and the depression of NE release at terminals
      closely parallels the membrane-delimited inhibition of N-type Ca2+ currents in
      the soma.

PMID- 9037084
TI  - Molecular determinants of inactivation and G protein modulation in the
      intracellular loop connecting domains I and II of the calcium channel alpha1A
      subunit.
AB  - Synaptic transmission is regulated by G protein-coupled receptors whose
      activation releases G protein betagamma subunits that modulate presynaptic Ca2+
      channels. The sequence motif QXXER has been proposed to be involved in the
      interaction between G protein betagamma subunits and target proteins including
      adenylyl cyclase 2. This motif is present in the intracellular loop connecting
      domains I and II (L I-II) of Ca2+ channel alpha1A subunits, which are modulated
      by G proteins, but not in alpha1C subunits, which are not modulated. Peptides
      containing the QXXER motif from adenylate cyclase 2 or from alpha1A block G
      protein modulation but a mutant peptide containing the sequence AXXAA does not,
      suggesting that the QXXER-containing peptide from alpha1A can competitively
      inhibit Gbetagamma modulation. Conversion of the R in the QQIER sequence of
      alpha1A to E as in alpha1C slows channel inactivation and shifts the voltage
      dependence of steady-state inactivation to more positive membrane potentials.
      Conversion of the final E in the QQLEE sequence of alpha1C to R has opposite
      effects on voltage-dependent inactivation, although the changes are not as large
      as those for alpha1A. Mutation of the QQIER sequence in alpha1A to QQIEE enhanced
      G protein modulation, and mutation to QQLEE as in alpha1C greatly reduced G
      protein modulation and increased the rate of reversal of G protein effects. These
      results indicate that the QXXER motif in L I-II is an important determinant of
      both voltage-dependent inactivation and G protein modulation, and that the amino
      acid in the third position of this motif has an unexpectedly large influence on
      modulation by Gbetagamma. Overlap of this motif with the consensus sequence for
      binding of Ca2+ channel beta subunits suggests that this region of L I-II is
      important for three different modulatory influences on Ca2+ channel activity.

PMID- 9037085
TI  - Relative numbers of cortical and brainstem inputs to the lateral geniculate
      nucleus.
AB  - Terminals of a morphological type known as RD (for round vesicles and dense
      mitochondria, which we define here as the aggregate of types formerly known as
      RSD and RLD, where "S" is small and "L" is large) constitute at least half of the
      synaptic inputs to the feline lateral geniculate nucleus, which represents the
      thalamic relay of retinal input to cortex. It had been thought that the vast
      majority of these RD terminals were of cortical origin, making the
      corticogeniculate pathway by far the largest source of input to geniculate relay
      cells. However, another source of RD terminals recently identified derives from
      cholinergic cells of the brainstem parabrachial region. (These cells also contain
      NO.) We used techniques of electron microscopy to determine quantitatively the
      relative contribution of cortex and brainstem to the population of RD terminals.
      We identified corticogeniculate terminals by orthograde transport of biocytin
      injected into the visual cortex and identified brainstem terminals by
      immunocytochemical labeling for choline acetyltransferase or brain NO synthase
      (the synthesizing enzymes for acetylcholine and NO, respectively). We estimated
      the relative numbers of corticogeniculate and brainstem terminals with a two-step
      algorithm: First, we determined the relative probability of sampling each
      terminal type in our material, and then we calculated what mixture of identified
      corticogeniculate and brainstem terminals was needed to recreate the size
      distribution of the parent RD terminal population. We conclude that brainstem
      terminals comprise roughly one-half of the RD population. Thus, the cortical
      input is perhaps half as large and the brainstem input is an order of magnitude
      larger than had been thought. This further suggests that the brainstem inputs
      might play a surprisingly complex and subtle role in the control of the
      geniculocortical relay.

PMID- 9037086
TI  - Brain-derived neurotrophic factor regulates expression of androgen receptors in
      perineal motoneurons.
AB  - Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) express androgen
      receptors and innervate striated muscles attached to the penis. Previous studies
      indicated that androgen receptor immunoreactivity in the SNB motoneurons
      decreases after axotomy and returns to normal only in motoneurons allowed to
      reinnervate their muscle targets, suggesting that neuron-target interactions play
      a role in regulating steroid receptor expression in the central nervous system.
      This study demonstrates that (i) silencing the SNB neuromuscular system with
      tetrodotoxin did not affect androgen receptor expression in these motoneurons,
      suggesting that the regulation of androgen receptor is activity-independent; (ii)
      disruption of axonal transport with vinblastine caused a down-regulation of
      androgen receptor expression in the SNB motoneurons; and (iii) treatment with
      brain-derived neurotrophic factor, but not ciliary neurotrophic factor,
      neurotrophin-4, or glial cell line-derived neurotrophic factor, reversed the
      axotomy-induced down-regulation of androgen receptor expression. These findings
      demonstrate neurotrophin regulation of steroid receptor expression in the central
      nervous system in vivo.

PMID- 9037088
TI  - Pleiotropic effects of a disrupted K+ channel gene: reduced body weight, impaired
      motor skill and muscle contraction, but no seizures.
AB  - To investigate the roles of K+ channels in the regulation and fine-tuning of
      cellular excitability, we generated a mutant mouse carrying a disrupted gene for
      the fast activating, voltage-gated K+ channel Kv3.1. Kv3.1-/- mice are viable and
      fertile but have significantly reduced body weights compared with their Kv3.1+/-
      littermates. Wild-type, heterozygous, and homozygous Kv3.1 channel-deficient mice
      exhibit similar spontaneous locomotor and exploratory activity. In a test for
      coordinated motor skill, however, homozygous Kv3.1-/- mice perform significantly
      worse than their heterozygous Kv3.1+/- or wild-type littermates. Both fast and
      slow skeletal muscles of Kv3.1-/- mice are slower to reach peak force and to
      relax after contraction, consequently leading to tetanic responses at lower
      stimulation frequencies. Both mutant muscles generate significantly smaller
      contractile forces during a single twitch and during tetanic conditions. Although
      Kv3.1-/- mutants exhibit a normal auditory frequency range, they show significant
      differences in their acoustic startle responses. Contrary to expectation,
      homozygous Kv3.1-/- mice do not have increased spontaneous seizure activity.

PMID- 9037087
TI  - Identification of PN1, a predominant voltage-dependent sodium channel expressed
      principally in peripheral neurons.
AB  - Membrane excitability in different tissues is due, in large part, to the
      selective expression of distinct genes encoding the voltage-dependent sodium
      channel. Although the predominant sodium channels in brain, skeletal muscle, and
      cardiac muscle have been identified, the major sodium channel types responsible
      for excitability within the peripheral nervous system have remained elusive. We
      now describe the deduced primary structure of a sodium channel, peripheral nerve
      type 1 (PN1), which is expressed at high levels throughout the peripheral nervous
      system and is targeted to nerve terminals of cultured dorsal root ganglion
      neurons. Studies using cultured PC12 cells indicate that both expression and
      targeting of PN1 is induced by treatment of the cells with nerve growth factor.
      The preferential localization suggests that the PN1 sodium channel plays a
      specific role in nerve excitability.

PMID- 9037089
TI  - Co-expression of the neuronal alpha7 and L247T alpha7 mutant subunits yields
      hybrid nicotinic receptors with properties of both wild-type alpha7 and alpha7
      mutant homomeric receptors.
AB  - Injection of cDNA encoding the neuronal alpha7 subunit into Xenopus oocytes
      yields homomeric receptors showing responses to AcCho that have low affinity,
      fast desensitization, nonlinear current-voltage (I-V) relation, and sensitivity
      to alpha-bungarotoxin (alpha-BTX) and 5-hydroxytryptamine (5HT), both substances
      acting as antagonists. Mutation of the Leu-247, located in the channel domain,
      changes 5HT from an antagonist to an agonist, slows the rate of desensitization,
      renders the I-V relation linear, and increases the affinity for acetylcholine
      (AcCho). A study was made of receptors expressed after injecting Xenopus oocytes
      with mixtures of cDNAs encoding the wild-type alpha7 (WT alpha7) and the L247T
      alpha7 mutated nicotinic AcCho receptors (nAcChoRs). The receptors expressed were
      again blocked by alpha-bungarotoxin (100 nM) but exhibited both WT alpha7 and
      alpha7 mutant functional characteristics. Out of eight different types of hybrid
      receptors identified, most were inhibited by 5HT (1 mM) and showed low
      sensitivity to AcCho, like the WT alpha7 receptors, but exhibited a slow rate of
      desensitization and an I-V relation similar to those of alpha7 mutant receptors.
      Together, these findings indicate that the increased nAcChoR affinity and the
      decreased nAc-ChoR desensitization after Leu-247 mutation are uncoupled events.
      We propose that receptor diversity is predicted by permutations of WT alpha7 and
      L247T alpha7 subunits in a pentameric symmetrical model and that even partial
      replacement of Leu-247 with a polar residue within the leucine ring in the
      channel domain considerably influences the properties of neuronal alpha7
      nAcChoRs.

PMID- 9037090
TI  - Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive
      responses and morphine-induced analgesia.
AB  - Morphine produces analgesia at opiate receptors expressed in nociceptive
      circuits. mu, delta, and kappa opiate receptor subtypes are expressed in circuits
      that can modulate nociception and receive inputs from endogenous opioid
      neuropeptide ligands. The roles played by each receptor subtype in nociceptive
      processing in drug-free and morphine-treated states have not been clear, however.
      We produced homologous, recombinant mu, opiate receptor, heterozygous and
      homozygous knockout animals that displayed approximately 54% and 0% of wild-type
      levels of mu receptor expression, respectively. These mice expressed kappa
      receptors and delta receptors at near wild-type levels. Untreated knockout mice
      displayed shorter latencies on tail flick and hot plate tests for spinal and
      supraspinal nociceptive responses than wild-type mice. These findings support a
      significant role for endogenous opioid-peptide interactions with mu opiate
      receptors in normal nociceptive processing. Morphine failed to significantly
      reduce nociceptive responses in hot plate or tail flick tests of homozygous mu
      receptor knockout mice, and heterozygote mice displayed right and downward shifts
      in morphine analgesia dose-effect relationships. These results implicate
      endogenous opioid-peptide actions at mu opiate receptors in several tests of
      nociceptive responsiveness and support mu receptor mediation of morphine-induced
      analgesia in tests of spinal and supraspinal analgesia.

PMID- 9037091
TI  - Amyloid precursor protein processing and A beta42 deposition in a transgenic
      mouse model of Alzheimer disease.
AB  - The PDAPP transgenic mouse, which overexpresses human amyloid precursor protein
      (APP717V-->F), has been shown to develop much of the pathology associated with
      Alzheimer disease. In this report, levels of APP and its amyloidogenic
      metabolites were measured in brain regions of transgenic mice between 4 and 18
      months of age. While absolute levels of APP expression likely contribute to the
      rate of amyloid beta-peptide (Abeta) deposition, regionally specific factors also
      seem important, as homozygotic mice express APP levels in pathologically
      unaffected regions in excess of that measured in certain amyloid plaque-prone
      regions of heterozygotic mice. Regional levels of APP and APP-beta were nearly
      constant at all ages, while A beta levels dramatically and predictably increased
      in brain regions undergoing histochemically confirmed amyloidosis, most notably
      in the cortex and hippocampus. In hippocampus, A beta concentrations increase 17
      fold between the ages of 4 and 8 months, and by 18 months of age are over 500
      fold that at 4 months, reaching an average level in excess of 20 nmol of A beta
      per g of tissue. A beta1-42 constitutes the vast majority of the depositing A
      beta species. The similarities observed between the PDAPP mouse and human
      Alzheimer disease with regard to A beta42 deposition occurring in a temporally
      and regionally specific fashion further validate the use of the model in
      understanding processes related to the disease.

PMID- 9037093
TI  - Characterization of the permeability barrier of human skin in vivo.
AB  - Attenuated-total-reflectance Fourier-transform-infrared spectroscopy has been
      used to rapidly and noninvasively quantify in vivo the uptake of a chemical into
      the outermost, and least permeable, layer of human skin (the stratum corneum).
      The objective of the experiment was to develop a general model to predict the
      rate and extent of chemical absorption for diverse exposure scenarios from
      simple, and safe, short-duration studies. Measurement of the concentration
      profile of the chemical in the stratum corneum, and analysis of the data using
      the unsteady-state diffusion equation, enabled estimation of the permeability
      coefficient and calculation of the time required to achieve maximal transdermal
      flux. Validation of the spectroscopic technique employed was established, and
      quantitation of chemical uptake into the stratum corneum was confirmed
      independently using trace amounts of radiolabeled chemical in conjunction with
      liquid scintillation counting and accelerator mass spectrometry. The results
      presented have pharmacological and toxicological implications, as the technology
      lends itself both to the prediction of transdermal drug delivery, and the
      feasibility of this route of administration, and to the assessment of risk after
      dermal contact with toxic chemicals.

PMID- 9037092
TI  - Interconversion of red opsin isoforms by the cyclophilin-related chaperone
      protein Ran-binding protein 2.
AB  - Ran-binding protein 2 (RanBP2) (type II) is a retinal cyclophilin-related protein
      that binds Ran-GTPase. Type I cyclophilin is a shorter, alternatively spliced
      isoform of RanBP2. Recently, we showed that the Ran-binding domain 4
      (RBD4)/cyclophilin (CY) supradomain of RanBP2 acts both in vitro and in vivo as a
      specific chaperone for bovine red/green opsin (R/G opsin). R/G opsin undergoes a
      stable modification of its electrophoretic mobility upon binding to RanBP2. This
      modification is likely due to cis-trans isomerization of one or more proline
      residues in the opsin protein. Here, we show that expression of human red opsin
      in Escherichia coli and COS cells results in the production of still a third
      electrophoretic variant of this protein. This variant was converted to the RBD4
      binding-competent form of opsin through direct interaction with RBD4/CY, both in
      vivo and in vitro. We suggest that these distinct opsin species may represent
      kinetically or thermodynamically trapped prolyl conformers that can be
      interconverted by concerted action of the RBD4 and CY domains of RanBP2. We also
      show that the C-terminal half of RBD4 is the binding domain for bovine R/G opsin
      and that coexpression of human red opsin with type I cyclophilin in vivo enhances
      the production of functional visual pigment. These observations imply that prolyl
      isomerization may have importance beyond its role in protein folding, possibly as
      a molecular switch modulated by cyclophilin for the loading of opsin onto RanBP2
      during visual pigment processing in cones.

PMID- 9037094
TI  - Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly
      rectifying potassium channel.
AB  - Ion selectivity is critical for the biological functions of voltage-dependent
      cation channels and is achieved by specific ion binding to a pore region called
      the selectivity filter. In voltage-gated K+, Na+ and Ca2+ channels, the
      selectivity filter is formed by a short polypeptide loop (called the H5 or P
      region) between the fifth and sixth transmembrane segments, donated by each of
      the four subunits or internal homologous domains forming the channel. While
      mutagenesis studies on voltage-gated K+ channels have begun to shed light on the
      structural organization of this pore region, little is known about the physical
      and chemical interactions that maintain the structural stability of the
      selectivity filter. Here we show that in an inwardly rectifying K+ (IRK) channel,
      IRK1, short range interactions of an ion pair in the H5 pore loop are crucial for
      pore structure and ion permeation. The two residues, a glutamate and an arginine,
      appear to form exposed salt bridges in the tetrameric channel. Alteration or
      disruption of such ion pair interactions dramatically alters ion selectivity and
      permeation. Since this ion pair is conserved in all IRK channels, it may
      constitute a general mechanism for maintaining the stability of the pore
      structure in this channel superfamily.

PMID- 9037095
TI  - Dependence of intracellular signaling and neurosecretion on phospholipase D
      activation in immortalized gonadotropin-releasing hormone neurons.
AB  - The excitability of gonadotropin-releasing hormone (GnRH) neurons is essential
      for episodic neuropeptide release, but the mechanism by which electrical activity
      controls GnRH secretion is not well characterized. The role of phospholipase D
      (PLD) in mediating the activity-dependent secretory pathway was investigated in
      immortalized GT1 neurons, which both secrete GnRH and express GnRH receptors.
      Activation of these Ca2+-mobilizing receptors was associated with transient
      hyperpolarization of GT1 cells, followed by sustained firing of action
      potentials. This was accompanied by an increase in PLD activity, as indicated by
      elevated phosphatidylethanol (PEt) production. GnRH-induced PEt production was
      reduced by inhibition of phospholipase C-dependent phosphoinositide hydrolysis by
      U73122 and neomycin, suggesting that signaling from phospholipase C led to
      activation of PLD. The intermediate role of protein kinase C (PKC) in this
      process was indicated by the ability of phorbol 12-myristate 13-acetate to induce
      time- and dose-dependent increases in PEt and diacylglycerol, but not inositol
      trisphosphate, and by reduction of GnRH-induced PEt accumulation in PKC-depleted
      cells. Consistent with the role of action potential-driven Ca2+ entry in this
      process, agonist-induced PLD activity was also reduced by nifedipine and low
      extracellular Ca2+. Inhibition of the PLD pathway by ethanol and propranolol
      reduced diacylglycerol production and caused a concomitant fall in GnRH release.
      These data indicate that voltage-gated Ca2+ entry and PKC act in an independent
      but cooperative manner to regulate PLD activity, which contributes to the
      secretory response in GT1 cells. Thus, the electrical activity of the GnRH
      secreting neuron participates in the functional coupling between GnRH receptors
      and PLD pathway.

PMID- 9037098
TI  - Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic
      acid production.
AB  - The function of acyl carrier protein (ACP) in mitochondria isolated from pea
      leaves has been investigated. When pea leaf mitochondria were labeled with [2
      14C] malonic acid in vitro, radioactivity was incorporated into fatty acids, and,
      simultaneously, ACP was acylated. [1-14C]Acetate was much less effective as a
      precursor for fatty acid synthesis, suggesting that mitochondria do not possess
      acetyl-CoA carboxylase. The incorporation of radioactivity from [2-14C]malonate
      into fatty acids and the labeling of ACP were inhibited by cerulenin and required
      ATP and Mg2+. These findings indicate that plant mitochondria contain not only
      ACP, but all enzymes required for de novo fatty acid synthesis. Over 30% of the
      radioactive products from pea mitochondria labeled with [2-14C]malonate were
      recovered in H protein, which is a subunit of glycine decarboxylase and contains
      lipoic acid as an essential constituent. In similar experiments, the H protein of
      Neurospora mitochondria was also labeled by [2-14C]malonate. The labeling of pea
      H protein was inhibited by addition of cerulenin into the assay medium. Together,
      these findings indicate that ACP is involved in the de novo synthesis of fatty
      acids in plant mitochondria and that a major function of this pathway is
      production of lipoic acid precursors.

PMID- 9037100
TI  - Analysis of frequency (frq) clock gene homologs: evidence for a helix-turn-helix
      transcription factor.
AB  - The frq gene plays a key role in the organization of the Neurospora crassa
      circadian clock. Our previous analysis of a C-terminal fragment of the putative
      FRQ protein suggested it is a nuclear transcription factor but did not identify a
      known DNA-binding domain. If the hypothesis is correct that FRQ is a
      transcription factor, sequences consistent with this function should be conserved
      in distantly related species. To investigate, we have cloned frq homologs from
      other filamentous fungi including Chromocrea spinulosa, and Leptosphaeria
      australiensis. Alignment of the Leptosphaeria and Chromocrea proteins with the
      published (complete) sequences for Neurospora crassa and Sordaria fimicola shows
      that they are respectively about 47%, and 43%, identical to both Neurospora and
      Sordaria. The alignment identifies several short regions of high conservation
      punctuated by regions showing near total divergence. Sequences consistent with
      FRQ being a transcription factor are generally conserved. Most importantly, we
      show that a highly conserved segment of the protein has strongly predicted helix
      turn-helix (HTH) structure as supported by three independent methods. Further,
      this segment shows the defining sequence characteristics of known HTH DNA-binding
      domains. Amino acids at positions altered in frq mutant alleles are conserved in
      all species examined. Transformation of the Neurospora frq9 (conditionally
      arrhythmic) mutant with the Chromocrea homolog rescued the pigmentation and
      conidiation defects of the mutant but not the circadian defect; the Leptosphaeria
      homolog failed to rescue any defect. Together, these data provide the first
      testable hypotheses concerning several specific aspects of FRQ structure and
      function.

PMID- 9037101
TI  - A locus coding for putative non-ribosomal peptide/polyketide synthase functions
      is mutated in a swarming-defective Proteus mirabilis strain.
AB  - We describe a large bacterial locus that, unusually, encodes components typically
      required for both the non-ribosomal synthesis of peptides and also
      polyketide/fatty acid synthase function. Two tandem ABC transporter genes in this
      putative nrp (non-ribosomal peptide/polyketide) operon suggest that the principal
      product may be secreted. Immediately distal to the nrp operon is a gene, irpP,
      encoding a small peptide similar to the Bacillus ComX pheromone that in its
      mature, extracellular form increases expression of unlinked non-ribosomal peptide
      synthesis genes. Transcription of both the nrp operon and irpP was up-regulated
      in iron-limiting culture conditions, consistent with the presence of a putative
      Fur repressor-binding site 5' of irpP. The locus was isolated from Proteus
      mirabilis as the site of a TnphoA insertion causing impaired swarm cell
      differentiation and an aberrant swarming pattern. The mutation was in one of the
      transporter genes, but a comparable swarming defect resulted from interposon
      disruption of the putative nrp synthetase gene.

PMID- 9037102
TI  - Characterization of upstream activating sequences involved in activation and
      regulation of pho4 expression in Schizosaccharomyces pombe.
AB  - In this study, a short region of the pho4 promoter located just upstream of the
      TATA box, called the upstream activating sequence (UAS), was shown to be
      responsible for both activation and regulation of pho4 expression in
      Schizosaccharomyces pombe. This cis-acting sequence is able to activate
      transcription when placed upstream of the minimal promoter of the constitutively
      expressed adh gene, and to ensure regulation by thiamine. The organisation of the
      pho4 promoter is remarkable in that UAS and TATA box are very closely associated.
      This proximity appears to be essential for efficient transcriptional regulation.
      Indeed, only slight variations in transcript levels were observed under
      derepression conditions when the UAS was moved away from the TATA box, while
      regulation of transcript levels appeared to be strongly affected. This
      observation suggests the existence of a negative regulatory element whose action
      requires very close association of UAS and TATA box. Surprisingly, when UAS was
      moved about 40 bp away from the adh TATA box, residual but very significant
      repression of gene expression by thiamine, which apparently does not result from
      transcriptional regulation, was revealed by measuring protein production. These
      data prompted us to hypothesize the existence of two distinct and cooperative
      mechanisms of regulation involving specific factor binding to the UAS, the first
      one controlling transcript levels and the second acting posttranscriptionally.

PMID- 9037103
TI  - UBI4, the polyubiquitin gene of Saccharomyces cerevisiae, is a heat shock gene
      that is also subject to catabolite derepression control.
AB  - Carbon and nitrogen regulation of UBI4, the stress-inducible polyubiquitin gene
      of Saccharomyces cerevisiae, was investigated using a UBI4 promoter-LacZ fusion
      gene (UBI4-LacZ). Expression of this gene in cells grown on different media
      indicated that the UBI4 promoter is more active during growth on respiratory than
      on fermentable carbon sources but is not subject to appreciable control by
      nitrogen catabolite repression. UBI4-LacZ expression was virtually identical in
      cells having constitutively high (ras2, sra1-13) or constitutively low (ras2)
      levels of cyclic AMP-dependent protein kinase activity, indicating that this
      kinase does not exert a major influence on UBI4 expression. Catabolite
      derepression control of the UBI4 promoter was confirmed by measurements of UBI4
      LacZ expression in hap mutant and wild-type strains before and after transfer
      from glucose to lactate. Mutagenesis of the perfect consensus for HAP2/3/4
      complex binding at position -542 resulted in considerable reduction of UBI4
      promoter derepression with respiratory adaptation in HAP wild-type cells and
      abolished the reduced UBI4-LacZ derepression normally seen when aerobic cultures
      of the hap1 mutant are transferred from glucose to lactate. This HAP2/3/4 binding
      site is therefore a major element contributing to catabolite derepression of the
      UBI4 promoter, although data obtained with hapl mutant cells indicated that HAP1
      also contributes to this derepression. The HAP2/3/4 and HAP1 systems are normally
      found to activate genes for mitochondrial (respiratory) functions. Their
      involvement in mediating higher activity of the UBI4 promoter during respiratory
      growth may reflect the contribution of UBI4 expression to tolerance of oxidative
      stress.

PMID- 9037104
TI  - The 28.5-kDa iron-sulfur protein of mitochondrial complex I is encoded in the
      nucleus in plants.
AB  - The intrinsic 28.5-kDa iron-sulfur protein of complex I in the mitochondrial
      respiratory chain is encoded in the nucleus in animals and fungi, but specified
      by a mitochondrial gene in trypanosomes. In plants, the homologous protein is now
      found to be encoded by a single-copy nuclear gene in Arabidopsis thaliana and by
      two nuclear genes in potato. The cysteine motifs involved in binding two iron
      sulfur clusters are conserved in the plant protein sequences. The locations of
      the seven introns, with sizes between 60 and 1700 nucleotides, are identical in
      the A. thaliana and the two potato genes, while their primary sequences diverge
      considerably. The A + T contents of the intron sequences range between 61% and
      73%, as is characteristic for dicot plants, but are in some instances not higher
      than in the adjacent exons. Here, differences in T content may instead serve to
      discriminate exons and introns. In potato, both genes are expressed, with the
      highest levels found in flowers. Sequence similarities between the homologous
      nuclear and mitochondrial genes indicate that the nuclear forms in animals and
      plants originate from the endosymbiont genome.

PMID- 9037105
TI  - Tomato chromosome 1: high resolution genetic and physical mapping of the short
      arm in an interspecific Lycopersicon esculentum x L. peruvianum cross.
AB  - A detailed map of part of the short arm of chromosome 1 proximal to the Cf-4/Cf-9
      gene cluster was generated by using an F2 population of 314 plants obtained from
      the cross between the remotely related species Lycopersicon esculentum and L.
      peruvianum. Six markers that cosegregate in an L. esculentum x L. pennellii F2
      population showed high recombination frequencies in the present interspecific
      population, spanning an interval of approximately 13 cM. Physical distances
      between RFLP markers were estimated by pulsed field gel electrophoresis of high
      molecular-weight DNA and by identifying YACs that recognized more than one RFLP
      marker. In this region 1 cM corresponded to 55-110 kb. In comparsion with the
      value of 730 kb per cM averaged over the entire genome, this reflects the
      remarkably high recombination frequencies in this region in the hybrid L.
      esculentum x L. peruvianum progeny population. The present data underline the
      fact that recombination is not a process that occurs randomly over the entire
      genome, but can vary dramatically in intensity between chromosomal regions and
      among populations.

PMID- 9037106
TI  - Molecular cloning of a gene required for DNA replication in Ustilago maydis.
AB  - TSD2, a gene necessary for DNA synthesis in Ustilago maydis, was cloned by
      complementation of the temperature sensitive growth defect of a mutant known
      previously as pol1-1 and renamed here tsd2-1. Linkage analysis established that
      the cloned fragment contained an allele of tsd2-1 and not a suppressor. DNA
      sequence determination of the cloned DNA fragment indicated the presence of a
      single large uninterrupted open reading frame capable of encoding a protein of
      845 amino acids without homology to any known gene involved in DNA synthesis.
      TSD2 was found to be cell cycle-regulated and mRNA levels peaked in early S or G1
      phase.

PMID- 9037107
TI  - The Kluyveromyces lactis equivalent of casein kinase I is required for the
      transcription of the gene encoding the low-affinity glucose permease.
AB  - The RAG8 gene of Kluyveromyces lactis, which is one of the genes controlling the
      expression of the low-affinity carrier gene RAG1, has been cloned by in vivo
      complementation of the rag8 mutation. The sequence of Rag8p (535 amino acids),
      deduced from the nucleotide sequence of the cloned RAG8 gene, has been found to
      share a high degree of identity with the two casein kinases I of Saccharomyces
      cerevisiae, Yck1p and Yck2p, encoded by YCK1 and YCK2: the proteins are 65-66%,
      identical overall and show 89-90% identity in the kinase domain. The finding that
      the RAG8 gene of K. lactis cloned in a centromeric vector was able to complement
      the growth defect of a yck1 delta yck2(ts) mutant of S. cerevisiae strongly
      suggested that Rag8p is a casein kinase I. In contrast to the S. cerevisiae
      homologs, the RAG8 gene of K. lactis seems to be an essential single-copy gene,
      as shown by Southern blot experiments and the lethality of the rag8 null
      mutation. Northern blot analysis showed that the transcription of the RAG8 gene
      was higher on glucose media than in cells grown on a non-fermentable carbon
      source.

PMID- 9037108
TI  - Chromosomal deletions in Streptomyces griseus that remove the afsA locus.
AB  - We have recently constructed a physical map of the Streptomyces griseus 2247
      genome using the restriction enzymes AseI and DraI, which revealed that this
      strain carries a 7.8 Mb linear chromosome. Based on this map, precise
      macrorestriction fragment and cosmid maps were constructed for both ends of the
      chromosome, which localized the afsA gene 150 Kb from the left end. Two afsA-
      mutants were found to have suffered chromosomal deletions that removed the afsA
      locus. The sizes of the deletions were 20 and 130 Kb at the right end and 180 and
      350 kb at the left end, respectively. Hybridization experiments using cosmids
      carrying a deletion endpoint indicated that the ends of the chromosome in the
      mutants were fused to form a circular chromosome.

PMID- 9037109
TI  - The Listeria monocytogenes gene ctpA encodes a putative P-type ATPase involved in
      copper transport.
AB  - A Tn917 transposon derivative was used to construct a lacZ transcriptional fusion
      mutant in Listeria monocytogenes DRDC8 that displayed increased beta
      galactosidase activity in response to cation stress. A 4.3 kb fragment of L.
      monocytogenes chromosomal DNA flanking the lacZ fusion was cloned and sequenced.
      A 1962 bp open reading frame was identified, and designated ctpA. Analysis of the
      deduced 653 amino acid sequence revealed significant similarity to the family of
      ATP-dependent enzymes involved in copper transport in prokaryotes and eukaryotes.
      CtpA is distinctive by virtue of an N-terminal truncation in the domain
      responsible for cation binding. Growth of ctpA insertion mutants was restricted
      by the copper-chelating agent 8-hydroxyquinoline. DNA/RNA hybridisation studies
      revealed that levels of ctpA mRNA were increased following growth in media
      containing low and high copper concentrations. These results suggest the
      isolation of a region of DNA that encodes a novel copper-transporting system in
      L. monocytogenes.

PMID- 9037110
TI  - The S-adenosyl-L-homocysteine hydrolase of Drosophila melanogaster:
      identification, deduced amino acid sequence and cytological localization of the
      structural gene.
AB  - S-adenosyl-L-homocysteine hydrolase (AdoHcyase, EC 3.3.1.1) catalyzes the
      hydrolysis of S-adeno-syl-L-homocysteine to adenosine and homocysteine and thus
      plays a crucial role in normal cellular metabolism. We have isolated the cDNA for
      Drosophila melanogaster AdoHcyase by screening a Drosophila ovarian expression
      library. The 1584-nucleotide cDNA encodes a protein of 431 amino acids, showing
      80.5% identity with human AdoHcyase. Southern analysis of genomic DNA and in situ
      hybridization to salivary gland chromosomes indicate that a single gene encodes
      the D. melanogaster AdoHcyase. The gene resides in region 13C1-2 on the X
      chromosome. Transcript analysis shows a single AdoHcyase mRNA present in
      unfertilized eggs, and, at a more or less constant level of expression, in all
      developmental stages tested, ranging from early embryos to adults. The deduced
      amino acid sequence was compared to a putative AdoHcyase-like protein encoded by
      a cDNA mapping to the 89E region of the second chromosome and showing much lower
      similarity to known AdoHcyases. We discuss the hypothesis that a sequence that
      originated by duplication of an ancestral AdoHcyase gene has, in the course of
      evolution, been recruited to supply a different function.

PMID- 9037111
TI  - Organisation of the bph gene cluster of transposon Tn4371, encoding enzymes for
      the degradation of biphenyl and 4-chlorobiphenyl compounds.
AB  - Tn4371 is a 55 kb transposon which encodes enzymes for the degradation of
      biphenyl and 4-chlorobiphenyl compounds into benzoate and 4-chlorobenzoate
      derivatives. We constructed a cosmid library of Tn4371 DNA. The bph genes
      involved in biphenyl/4-chlorobiphenyl degradation were found to be clustered in
      the middle of the transposon. Sequencing revealed an organisation of the bph
      genes similar to that previously found in Pseudomonas sp. KKS102, i.e. the bphEGF
      genes are located upstream of bphA1A2A3 and bphA4 is separated from bphA1A2A3 by
      bphBCD. Consensus sequences for sigma54-associated RNA polymerase were found
      upstream of bphA1 and bphEGF. Plasmid RP4::Tn4371 was transferred into a mutant
      of Alcaligenes eutrophus H16 lacking sigma54. In contrast to wild-type H16
      exconjugants, the sigma54 mutant exconjugants could not grow on biphenyl,
      indicating the dependence of Tn4371 bph gene expression on sigma54. The Tn4371
      encoded bph pathway was activated when biphenyl and various biphenyl-like
      compounds were present in the growth medium. Preliminary observations indicate
      the presence of a region outside the catabolic genes downstream of bphA4 which is
      involved in mediating at least the basal expression of BphC.

PMID- 9037112
TI  - Glutamic acid-371 of the barnase homology domain in RNA polymerase II is not
      required for SII-activated RNA cleavage.
AB  - RNA polymerase II contains a ribonuclease activity which is stimulated by the
      transcription elongation factor SII. This nuclease shortens the nascent RNA and
      facilitates relief of transcriptional arrest by allowing the enzyme to make
      multiple attempts to read through an obstacle to transcription. The catalytic
      center of this ribonuclease is unknown, although a region of the enzyme's second
      largest subunit shares local sequence similarly with barnase and other bacterial
      ribonucleases. To test the role of the barnase homology region in SII-activated
      cleavage, we engineered a single amino acid change in the Saccharomyces
      cerevisiae enzyme at a position homologous to a catalytic residue of barnase (Glu
      371) and has been suggested as a participant in active site chemistry of RNA
      polymerase II. We purified RNA polymerase II from mutant yeast and assayed its
      ability to cleave and re-extend the nascent RNA following SII treatment. We find
      no defects in this function of the mutant enzyme, suggesting that the barnase
      homology region does not represent the active site of the SII-activated nuclease.
      These mutant yeast cells were also resistant to mycophenolic acid, which slows
      the growth of some yeast mutants bearing elongation defective RNA polymerase II
      or mutant elongation factor SII.

PMID- 9037113
TI  - Unique genomic sequences in human chromosome 16p are conserved in the great apes.
AB  - In humans, acute myelomonocytic leukemia (AMML) with abnormal bone marrow
      eosinophilia is diagnosed by the presence of a pericentric inversion in
      chromosome 16, involving breakpoints p13;q23 [i.e., inv(16)(p13;q23)]. A
      pericentric inversion involves breaks that have occurred on the p and q arms and
      the segment in between is rotated 180 degrees and reattaches. The recent
      development of a "human micro-coatasome" painting probe for 16p contains unique
      DNA sequences that fluorescently label only the short arm of chromosome 16, which
      facilitates the identification of such inversions and represents an ideal tool
      for analyzing the "divergence/convergence" of the equivalent human chromosome 16
      (PTR 18, GGO 17 and PPY 19) in the great apes, chimpanzee, gorilla and orangutan.
      When the probe is used on the type of pericentric inversion characteristic of
      AMML, signals are observed on the proximal portions (the regions closest to the
      centromere) of the long and short arms of chromosome 16. The probe hybridized to
      only the short arm of all three ape chromosomes and signals were not observed on
      the long arms, suggesting that a pericentric inversion similar to that seen in
      AMML has not occurred in any of these great apes.

PMID- 9037114
TI  - Functional relationship between Escherichia coli RNase E and the CafA protein.
AB  - We analyzed the functional relationship between the Escherichia coli RNase E and
      the CafA protein, which show extensive sequence similarity. The temperature
      sensitive growth of the RNase E mutant strain ams1 was partially suppressed by
      multicopy plasmids bearing the cafA gene. Introduction of a cafA::cat mutation
      enhanced the temperature sensitivity of the ams1 mutant. These results suggest
      that there is a functional homology between these two proteins.

PMID- 9037115
TI  - The Aspergillus nidulans genes chsA and chsD encode chitin synthases which have
      redundant functions in conidia formation [corrected and republished article
      originally appeared in Mol Gen Genet 1996 Jun; 251(4):442-50].
AB  - We previously isolated three chitin synthase genes (chsA, chsB, and chsC) from
      Aspergillus nidulans. In the present work, we describe the isolation and
      characterization of another chitin synthase gene, named chsD, from A. nidulans.
      Its deduced amino acid sequence shows 56.7% and 55.9% amino acid identity,
      respectively, with Cal1 of Saccharomyces cerevisiae and Chs3 of Candida albicans.
      Disruption of chsD caused no defect in cell growth or morphology during the
      asexual cycle and caused no decrease in chitin content in hyphae. However, double
      disruption of chsA and chsD caused a remarkable decrease in the efficiency of
      conidia formation, while double disruption of chsC and chsD caused no defect.
      Thus it appears that chsA and chsD serve redundant functions in conidia
      formation.

PMID- 9037116
TI  - Coagulation disorders in thyroid diseases.

PMID- 9037117
TI  - Dendritic cells and macrophages in the pituitary and the gonads. Evidence for
      their role in the fine regulation of the reproductive endocrine response.
AB  - Blood monocytes are able to mature into macrophages as well as into dendritic
      cells. Dendritic cells and macrophages have mainly been studied for their
      function in the immune response, e.g. in the presentation of antigens to
      lymphocytes and in the phagocytosis/degradation of unwanted material. The cells
      are also, however, important producers of a variety of signalling molecules and
      hormones and are thus involved in other physiological functions such as wound
      healing, the regulation of the microcirculation and the regulation of the
      function and growth of endocrine cells. This review summarizes the existing
      evidence for a regulatory role of dendritic cells and macrophages in the function
      and growth of hormone-producing cells of the pituitary-gonadal axis. It focuses
      on the presence, localization and phenotype of dendritic cells and macrophages in
      the anterior pituitary and the gonads, the endocrine regulatory role of cytokines
      produced by these cells and the existence of putative feedback mechanisms between
      endocrine cells of the pituitary-gonadal axis and dendritic cells and
      macrophages. The recognition of a 'floating endocrine-regulatory force' of
      monocyte-derived cells that also plays a role in the initiation of immune
      responses has implications for our understanding of the pathogenesis of gonadal
      and pituitary autoimmune reactions.

PMID- 9037118
TI  - Vitamin D treatment of hypoparathyroid patients.

PMID- 9037119
TI  - Phaeochromocytoma: how to catch a moonbeam in your hand.

PMID- 9037121
TI  - The yin and the yang of the IGF system: immunological manifestations of GH
      resistance.

PMID- 9037120
TI  - GH and bone metabolism: the role of the vitamin D system.

PMID- 9037122
TI  - Diurnal blood pressure profile, autonomic neuropathy and nephropathy in diabetes.

PMID- 9037123
TI  - Cloning of the growth hormone secretagogues receptor cDNA: new evidence for a
      third endocrine pathway controlling growth hormone release.

PMID- 9037124
TI  - Mechanisms of glucose toxicity. New hope for prevention of diabetic
      complications?

PMID- 9037125
TI  - Male germ cell transplantation.

PMID- 9037126
TI  - Growth hormone increases serum 1,25-dihydroxyvitamin D levels and decreases 24,25
      dihydroxyvitamin D levels in children with growth hormone deficiency.
AB  - The influence of growth hormone (GH) on calcium-phosphorus metabolism and
      modulation of vitamin D metabolism has been demonstrated, but the mechanism
      remains unclear. We investigated the effect of a 6-month course of GH therapy on
      vitamin D and mineral metabolism in twelve GH-deficient children. Before GH
      therapy, levels of vitamin D metabolites and other biochemistry data were within
      normal ranges. All patients responded to GH therapy with increased growth
      velocity. 1,25-Dihydroxyvitamin D levels increased after 1 month of treatment and
      remained at these higher levels, with a significant increase found at 3 months (P
      < 0.05), whereas 24,25-dihydroxyvitamin D levels were decreased at 1 and 3
      months, the latter being a significant decrease (P < 0.05), and then returned to
      the baseline levels at 6 months. 25-Hydroxyvitamin D levels did not change
      significantly. A significant increase in serum insulin-like growth factor-I (IGF
      I) levels occurred during the 6 months of treatment (1 month, P < 0.01; 3 and 6
      months, P < 0.001). Serum parathyroid hormone (PTH) levels decreased
      significantly at 3 and 6 months (3 months, P < 0.01; 6 months, P < 0.05). Serum
      calcium and phosphorus levels did not change significantly. Significant increases
      were found in the urinary calcium/urinary creatinine ratio (3 and 6 months, P <
      0.05) and the percent tubular reabsorption of phosphorus levels (1 and 3 months,
      P < 0.05). The results of this study confirmed the actions of GH on renal tubules
      with increases in calcium excretion and phosphorus reabsorption, and indicate
      that the action of GH on modulating vitamin D metabolism may be IGF-I mediated,
      not PTH mediated.

PMID- 9037127
TI  - Effect of vitamin D treatment in hypoparathyroid patients: a study on calcium,
      phosphate and magnesium homeostasis.
AB  - AIM: This study was undertaken to examine the effects of long-term vitamin D
      treatment on calcium, phosphate and magnesium homeostasis at organ level in
      hypoparathyroid patients. METHODS: Fifteen vitamin D-treated hypoparathyroid
      patients were studied, eight of the patients in a combined 47Ca kinetic and
      calcium, phosphate and magnesium balance study. Results were compared with a
      matched control group of 12 normal individuals. RESULTS: All the patients had
      normal serum levels of calcium, phosphate and magnesium. Absolute intestinal
      calcium absorption was increased (P < 0.0001). Urinary calcium excretion was
      normal, but active tubular calcium reabsorption (TmCa/glomerular filtration rate)
      was low (P< 0.001). Bone resorption rates and bone mineralization rates were very
      low (P < 0.001 and P < 0.05). Twenty-four-hour urinary hydroxyproline excretion
      and serum cross-linked carboxyterminal telopeptide of type I were in the upper
      normal range. Serum alkaline phosphatase was normal, but serum carboxyterminal
      propeptide of human type I procollagen and serum osteocalcin were significantly
      reduced (P < 0.05). Calcium balance was positive and significantly different from
      controls (P < 0.001). All parameters from phosphate homeostasis were normal.
      Intestinal magnesium absorption was low though not significantly different from
      normal (P = 0.06). Urinary excretion of magnesium was not significantly higher
      than normal, but renal magnesium reabsorption was reduced (P <0.001). Magnesium
      balance was low, though the difference was not significant (P < 0.06).
      CONCLUSION: Long-term vitamin D treatment in hypoparathyroid patients resulted in
      a positive calcium balance. Bone turnover was very low. Results of bone markers
      and resorption rate were conflicting. Vitamin D treatment apparently normalized
      the abnormalities previously found in phosphate homeostasis of hypoparathyroid
      patients. Magnesium homeostasis was disturbed, with a more negative balance
      compared with normal subjects, implying a state of magnesium deficiency in these
      patients.

PMID- 9037128
TI  - Growth hormone binding protein and growth hormone availability in acromegalic
      patients treated with long-acting octreotide (Sandostatin-LAR).
AB  - OBJECTIVE: In the medical treatment of acromegaly different factors are
      influential; among these the impact on growth hormone binding protein (GHBP) has
      not been clarified. DESIGN: Twenty acromegalic patients and nineteen age- and
      gender-matched normal subjects participated in this study. The patients were
      treated for 21 months with depot long-acting microsphere-enclosed octreotide
      (Sandostatin-LAR). Previously, all the patients were treated s.c. with octreotide
      t.i.d. After a 2-week wash-out period (baseline) the patients received the first
      i.m. injection of the long-acting octreotide. The first two injections were
      administered at 60-day intervals; thereafter the injections were at 28-day
      intervals. METHODS: The levels of GHBP, complexed GHBP, growth hormone (GH) and
      insulin-like growth factor-I (IGF-I) were determined in fasting serum samples.
      RESULTS: In the 2-week wash-out period GHBP levels decreased from 1.13 +/- 0.17
      to 0.92 +/- 0.15 nmol/l (P < 0.05). During the 21-months treatment, GHBP
      increased again to 1.10 +/- 0.16 nmol/l. In the age- and gender-matched control
      group GHBP levels were significantly higher at all times (1.95 +/- 0.21 nmol/l.
      P(all) < 0.02). Mean levels of 8-h GH decreased from 12.6 +/- 2.58 microg/l at
      baseline to 1.97 +/- 0.20 microg/l after 21 months of treatment (P < 0.05). Mean
      8-h GH levels were unchanged during long-acting octreotide treatment compared
      with levels during s.c. treatment (1.97 +/- 0.20 microg/l and 1.90 +/- 0.20
      microg/l respectively). In fasting blood samples GH-complexed GHBP ranged from
      13.8 +/- 2.4% (9 months) to 25.4 +/- 4.5% (baseline) of total GHBP. Serum IGF-I
      increased from 367 +/- 45 to 764 +/- 80 microg/l (P < 0.05) during the 2-week
      wash-out period and decreased to 290 +/- 35 microg/l (P < 0.05) after 21 months
      of treatment with long-acting octreotide. IGF-I levels after 21 months were
      significantly lower than during s.c. octreotide treatment (P < 0.05). CONCLUSION:
      Serum GHBP levels are similar during treatment with long-acting octreotide as
      compared with regular octreotide. Furthermore, significant changes in GHBP can
      occur within 2 weeks. Finally, in addition to the lowering effect on GH levels,
      the induced increase in GHBP levels may imply a further advantage in octreotide
      treatment of acromegaly. circulating GH bound to GHBP may less readily reach the
      tissues.

PMID- 9037129
TI  - Chromogranin A and chromogranin B are sensitive circulating markers for
      phaeochromocytoma.
AB  - Specific assays for measurements of circulating chromogranin (Cg) A, CgB, CgC and
      pancreastatin (Ps) have recently been developed. The aim of the present study was
      to investigate the usefulness of these markers in diagnosing and following the
      effects of treatment of patients with phaeochromocytoma, and to compare the
      results with those concerning other biochemical markers. CgA was elevated in
      19/21 (90%), CgB in 17/21 (81%), Ps in 9/21 (43%) and neuropeptide Y in 9/21
      (43%) of the patients. Urinary noradrenaline was increased in 19/21 (90%) and
      urinary adrenaline in 17/19 (89%) of the patients. All patients had increased
      levels of either urinary catecholamines or plasma chromogranins. In one patient
      levels of CgA, CgB and Ps were measured at frequent intervals before, during and
      after surgery. The CgA level fell to normal shortly after the tumour was removed,
      whereas the CgB level decreased towards normal over the course of several days.
      Significant correlation was observed between the contents of CgA and CgB in the
      tumour tissue and the plasma levels of CgA and CgB respectively. We conclude that
      CgA and CgB are sensitive circulating markers for phaeochromocytoma and that
      measurements of both urinary catecholamines and plasma chromogranins improve the
      diagnostic sensitivity. Furthermore, measurements of CgA may be useful in
      assessing the radicality of surgery in the early postoperative period.

PMID- 9037130
TI  - Infrequent mutations of p16INK4A and p15INK4B genes in human pituitary adenomas.
AB  - The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15
      inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively.
      Mutations and deletions of the p16INK4A gene have been found in melanomas and
      many other types of tumors. To assess the role of the p16INK4A and p15NK4B genes
      in tumorigenesis of the pituitary gland, 31 sporadic pituitary adenomas and 2
      pituitary adenomas in familial acrogigantism were examined for loss of
      heterozygosity on 9p21-22 and screened for mutations in the p161NK4A and p15INK4B
      genes. To identify pituitary adenomas which had lost 9p21-22, pituitary adenomas
      were genotyped with markers flanking the p16INK4A and p15INK4B loci. The
      frequency of mutations in coding regions of the p16INK4A and the p15INK4B genes
      in pituitary adenomas was determined with polymerase chain reaction-single strand
      conformation polymorphism analysis and sequencing of variants. Of the 33
      pituitary adenomas, two revealed loss of 9p21-22 sequences, but none of them had
      tumor-specific mutations. We conclude that mutations of the p16INK4A and p15INK4B
      genes are not required for tumorigenesis of the pituitary gland.

PMID- 9037131
TI  - Suppression of serum thyrotropin with thyroxine in patients with Graves' disease:
      effects on recurrence of hyperthyroidism and thyroid volume.
AB  - Based on findings that thyroxine may have a beneficial effect on the recurrence
      of Graves' hyperthyroidism, we prospectively studied the effects of a TSH
      suppressive treatment with thyroxine on the course of Graves' disease in fifty
      patients with recent onset of hyperthyroidism. After the normalization of serum
      tri-iodothyronine (T3) and thyroxine (T4) concentrations, one group of patients
      was randomly assigned to a combined treatment with carbimazole and a TSH
      suppressive dose of T4 for 12 months, followed by another 12 months of TSH
      suppressive therapy alone. The other group of patients also received carbimazole
      for one year, but T4 was only added as indicated to normalize elevated TSH serum
      concentrations, and patients received no therapy during the second year. By the
      end of the second year, a relapse of hyperthyroidism had occurred in 43% of the
      patients with and in 45% of the patients without suppressive T4 treatment. In
      those patients without a relapse of hyperthyroidism, initial thyroid size
      significantly (P = 0.01) decreased with time in both treatment groups. However,
      patients on suppressive T4 treatment tended to have a greater reduction in
      thyroid volume than patients with normal TSH serum concentrations (P = 0.05). In
      conclusion, we were unable to detect a preventive effect of exogenous TSH
      suppression on the recurrence of hyperthyroidism. However, our data suggest that
      TSH suppressive treatment may have a beneficial effect on thyroid enlargement in
      Graves' disease.

PMID- 9037132
TI  - Lipoprotein(a) increase associated with thyroid autoimmunity.
AB  - Conflicting results have been reported regarding serum lipoprotein(a) (Lp(a))
      concentrations in patients with hypothyroidism. We addressed the question whether
      thyroid autoimmunity could be associated with elevated Lp(a) values independent
      of the thyroid status. Lp(a) was measured by ELISA in 30 males, 29 premenopausal
      and 30 postmenopausal females positive for thyroid peroxidase- and/ or
      thyroglobulin-antibody (T-Abs) and normolipidemic, screened out respectively from
      428 male donors, 162 premenopausal donors and 108 postmenopausal females; they
      were compared with 65 males, 72 premenopausal and 48 postmenopausal females,
      negative for thyroid antibodies, normolipidemic and matched for age. T-Abs
      positive male donors showed serum Lp(a) concentrations significantly increased
      compared with males without T-Abs (mean 19.7 +/- 15.9 vs 12.7 +/- 17.5 mg/dl;
      median 17.0 vs 4.0 mg/dl; Mann Whitney U test: P = 0.0000). In premenopausal
      females no difference could be found between T-Abs-positive and T-Abs-negative
      subjects (mean 13.2 +/- 16.1 vs 12.3 +/- 13.9 mg/dl; median 5.2 vs 8.7 mg/dl),
      suggesting an Lp(a) lowering effect of estrogens. The study was, therefore,
      extended to postmenopausal females. Significantly elevated Lp(a) levels were
      found in 30 postmenopausal females with T-Abs when compared with 48
      postmenopausal females without T-Abs (40.0 +/- 34.2 mg/dl vs 20.7 +/- 19.3 mg/dl;
      median 32.0 vs 18.0 mg/dl; Mann Whitney U test: P = 0.0002). Finally, 21
      postmenopausal, normolipidemic, autoimmune hypothyroid patients on L-thyroxine
      and euthyroid compared with 48 postmenopausal females without T-Abs also showed
      increased serum levels of Lp(a) (mean 27.0 +/- 16.8 mg/dl vs 20.7 +/- 19.3 mg/dl,
      median 25.0 vs 18 mg/dl; Mann Whitney U test: P = 0.0024). Thyrotropin levels in
      all subjects and patients were within the normal range. In conclusion, our
      results in males and postmenopausal females with T-Abs and euthyroid show an
      association between thyroid autoimmunity and increased levels of Lp(a), while the
      results obtained in premenopausal females suggest that estrogens might interfere
      with the Lp(a) increase related to thyroid autoimmunity.

PMID- 9037133
TI  - Increased neutrophil insulin-like growth factor-I (IGF-I) receptor expression and
      IGF-I-induced functional capacity in patients with untreated Laron syndrome.
AB  - Insulin-like growth factor-I (IGF-I) is a growth hormone-dependent peptide with
      growth and immunoregulatory properties, and in Laron syndrome growth hormone
      insensitivity induces impaired production of IGF-I. In the present study we have
      determined the neutrophil expression of IGF-I receptors (IGF-I-Rs), as well as
      the IGF-I-induced priming of neutrophil functional capacity, in two children with
      Laron syndrome treated with recombinant human IGF-I, and in age-matched controls.
      Before treatment, the patient neutrophil expression of IGF-I-Rs was significantly
      increased. However, with replacement therapy the neutrophil IGF-I-R expression
      was downregulated to levels similar to those of the controls within one month. In
      the patients, the phagocytic capacity and oxidative burst of unprimed neutrophils
      were normal and similar to controls before the start of treatment. Moreover, IGF
      I efficiently primed both patient and control neutrophils to increase their
      phagocytic capacity and oxidative burst in vitro. However, before therapy, the
      priming response to IGF-I was significantly stronger in the neutrophils in the
      patients than in the controls. The present data support earlier studies by us and
      others demonstrating that IGF-I is a potent regulator of mature neutrophil
      function, but also suggest that these leukocytes may function normally in the
      presence of very low levels of IGF-I in vivo.

PMID- 9037134
TI  - Late post-prandial hypoglycaemia as the sole presenting feature of secreting
      pancreatic beta-cell adenoma in a subtotally gastrectomized patient.
AB  - In this paper we describe for the first time late post-prandial hypoglycaemia as
      the sole presenting feature of an insulinoma in a patient who had previously
      undergone subtotal gastrectomy. The symptoms of hypoglycaemia always occurred 1-3
      h after meals, not in the fasting state. Because of the history of gastrectomy
      and because post-prandial hypoglycaemia was reproduced by an oral glucose
      tolerance test, the diagnosis of reactive hypoglycaemia was made. Eighteen months
      later a fasting test was performed: venous plasma glucose decreased from 3.8
      mmol/l to 2.7 mmol/l between 14 and 20 h of fast while plasma immunoreactive
      insulin did not decrease and plateaued at 185 pmol/l. Plasma C-peptide (0.9
      nmol/l) and proinsulin (70 pmol/l, split 64, 65) were also elevated. All islet
      hormones increased in response to i.v. glucose and were suppressed after
      diazoxide. Although pre-operative procedures were negative in localizing an
      insulinoma, the patient underwent an operation and an insulinoma was detected at
      the body level of the pancreas. Thus, insulinoma should be considered in the
      differential diagnosis of reactive hypoglycaemia in gastrectomized patients.
      Response of islet hormones to glucose and their suppression by diazoxide are
      evidence of a secreting insulinoma even in the absence of preoperative
      localization of the pancreatic adenoma.

PMID- 9037135
TI  - Neuropsychological development in a child with early-treated congenital
      hypothyroidism as compared with her unaffected identical twin.
AB  - OBJECTIVE: Neonatal screening for congenital hypothyroidism (CH) prevents the
      serious neuropsychological features of CH, but the question remains whether
      intelligence and motor skills of CH children treated early are completely normal.
      DESIGN: In this report we describe the rare case of two genetically identical
      twins, only one of whom was affected by CH due to thyroid agenesis. L-Thyroxine
      (9 microg/kg body weight/day) therapy was initiated at 27 days of age and was
      adequate throughout the follow-up. METHODS: Neuropsychological evaluation was
      performed on the twins in parallel from 3 months to 8 years of age. RESULTS: The
      CH twin (NB) did not show major neuromotor impairments but, compared with the
      unaffected twin (EB), she had a slight delay in postural/motor achievements and
      in language development that completely disappeared at 8 years of age. On
      standardised tests of intelligence, NB was indistinguishable from control
      children but, compared with her twin, she had lower IQ scores in most testing
      occasions up to 7 years of age (NB = 108 vs EB = 115). School achievements of NB
      did not significantly differ from those of her classmates but, compared with her
      twin, she scored worse in writing, mechanical reading, verbal memory, and
      possibly in arithmetic. CONCLUSIONS: Because the twins were genetically and
      phenotypically identical, were raised in the same environment, and received a
      similar education, it is concluded that hypothyroidism in utero and in the first
      neonatal month was responsible for the lower neuropsychological achievements of
      the CH twin. While foetal hypothyroidism is at present unavoidable, earlier
      diagnosis and initiation of treatment in neonates with CH are important and
      highly recommended.

PMID- 9037136
TI  - Biologically active human islet amyloid polypeptide/amylin in transgenic mice.
AB  - OBJECTIVE: Human islet amyloid polypeptide (hIAPP), also named amylin, is a
      pancreatic beta cell protein implicated in the pathogenesis of pancreatic islet
      amyloid formation and type 2 diabetes mellitus. To study the (patho)physiological
      roles of hIAPP, we have generated transgenic mice that overexpress hIAPP mRNA, in
      relation to endogenous mouse IAPP (mIAPP) mRNA, in pancreatic beta cells. The
      biological activity of human and mouse IAPP derived from pancreatic extracts was
      determined. METHODS: Pancreatic and plasma extracts of transgenic and control
      mice were analyzed by reversed-phase high-performance liquid chromatography
      (HPLC) and radioimmunoassay, yielding a separation of hIAPP from mIAPP.
      Biological activity of immunoreactive human and mouse IAPP components derived
      from pancreatic extracts was assessed by calcitonin receptor-mediated stimulation
      of cyclic AMP accumulation in T47D human breast carcinoma cells. RESULTS: The
      predominant immunoreactive human and mouse IAPP gene products had the retention
      times on HPLC analysis of the corresponding synthetic peptides. The ratio of
      bioactive over immunoreactive hIAPP and mIAPP was 0.93 +/- 0.18 and 1.19 +/- 0.56
      respectively. In extracts of two plasma pools from 4 transgenic animals, hIAPP
      was 4.6- to 7-fold more abundant than mIAPP. CONCLUSION: This study has shown
      that correctly processed hIAPP produced in transgenic mouse pancreatic beta cells
      exhibits full biological activity. The results validate these transgenic mice for
      the study of (patho)physiological roles of hIAPP in vivo.

PMID- 9037137
TI  - Lack of suppressive action of luteal factors from sheep corpus luteum on LH
      response to exogenous LHRH in ovariectomized, pregnant and post-partum ewes.
AB  - In vivo studies have provided evidence of a non-steroidal factor from ovine
      corpora lutea (CL) of pregnancy called LH-release inhibiting factor (LH-RIF),
      which specifically inhibits tonic LH release without affecting FSH secretion. To
      study the possible pituitary site of action of LH-RIF and other factors from
      sheep CL of pregnancy, the LH response to LHRH was investigated in ovariectomized
      (OVX) ewes pretreated with ovine luteal extract (oLE) from CL of mid-pregnancy,
      and in pregnant and post-partum ewes from which the CL were removed at mid
      pregnancy. In view of the fact that human follicular fluid (hFF) contains a non
      steroidal factor, called gonadotrophin surge-attenuating factor, which attenuates
      the LHRH-induced LH release, it was clearly important to examine the LHRH-induced
      LH release in OVX ewes pretreated with oLE or hFF In experiment 1, the LH and FSH
      responses (the maximum LH and FSH concentrations, the time to maximum LH and FSH
      concentrations and the area under the LH and FSH response curves) to a single
      i.v. injection of 5 microg of the LHRH agonist buserelin was not significantly
      different between ewes pretreated with oLE and ewes pretreated with BSA. Although
      the LHRH-induced LH and FSH release was slightly attenuated in OVX ewes
      pretreated with hFF as compared with OVX ewes pretreated with BSA, the maximum LH
      and FSH concentrations and the area under the LH and FSH response curves were not
      significantly different between the two groups of ewes. In experiment 2, the LH
      responses to a single i.v. injection of 0.5 microg LHRH on days 80 and 100 of
      pregnancy were not significantly different between intact ewes and ewes from
      which the CL were removed on day 70 of pregnancy. In both groups of ewes the
      maximum LH concentration and the area under the LH response curve were
      significantly lower (P <0.02) on day 100 than on day 80 of pregnancy. In
      experiment 3, the LH responses to a single i.v. injection of 50 microg LHRH on
      day 140 of pregnancy and on day 10 post-partum were not significantly different
      between intact ewes and ewes from which the CL were removed on day 70 of
      pregnancy. In both groups of ewes the maximum LH concentration and the area under
      the LH response curve were significantly lower (P <0.01) on day 140 of pregnancy
      than on day 10 post-partum. These experiments provide evidence for a lack of
      suppressive action of luteal secretory products from the ovine CL of pregnancy on
      the pituitary LH response to LHRH in OVX, pregnant and post-partum ewes.

PMID- 9037138
TI  - The stimulatory effect of endothelin-1 on regenerating adrenal cortex is reversed
      by nifedipine.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor, was found to act in non-vascular
      tissues, for example it enhanced aldosterone output from adrenal zona
      glomerulosa. As the adrenal cortex is capable of regeneration after enucleation,
      it seemed of interest to study the effects of ET-1 on adrenocortical
      regeneration. The study was performed on adult rats subjected to left adrenal
      enucleation combined with contralateral adrenalectomy. Mitotic index was employed
      to assess the proliferation of regenerating adrenal cortex cells. Plasma
      corticosterone was measured by a standard RIA kit. ET-1 significantly raised the
      mitotic index of regenerating rat adrenal cortex by six days after surgery. On
      the other hand, nifedipine reduced the proliferation ratio and abolished the
      stimulatory influence of ET-1. Similarly, ET-1 enhanced corticosterone output
      from the regenerating adrenal cortex, and this could be prevented by the addition
      of nifedipine. This study has shown that ET-1 might act as a regulatory factor on
      the regenerating adrenal cortex via calcium channels.

PMID- 9037139
TI  - State of the art of the production of the antimalarial compound artemisinin in
      plants.
AB  - For more than three centuries we have relied on the extracts of the bark of
      Cinchona species to treat malaria. Now, it seems we may be changing to the leaves
      of a Chinese weed, Artemisia annua, and its active compound artemisinin.
      Artemisinin-derived drugs have been proved particularly effective treatments for
      severe malaria, even for multidrug-resistant malaria. However, this promising
      antimalarial compound remains expensive and is hardly available on a global
      scale. Therefore, many research groups have directed their investigations toward
      the enhancement of artemisinin production in A. annua cell cultures or whole
      plants in order to overproduce artemisinin or one of its precursors. This article
      provides a brief review of the state of art of the different aspects in A. annua
      research.

PMID- 9037140
TI  - Three differentially expressed S-adenosylmethionine synthetases from Catharanthus
      roseus: molecular and functional characterization.
AB  - We describe the molecular and functional characterization of three closely
      related S-adenosyl-L-methionine synthetase (SAMS) isoenzymes from Catharanthus
      roseus (Madagascar periwinkle). The genes are differentially expressed in cell
      cultures during growth of the culture and after application of various stresses
      (elicitor, nutritional down-shift, increased NaCl). Seedlings revealed organ
      specific expression and differential gene regulation after salt stress. A
      relationship analysis indicated that plant SAMS group in two main clusters
      distinguished by characteristic amino acid exchanges at specific positions, and
      this suggested differences in the enzyme properties or the regulation. SAMS1 and
      SAMS2 are of type I and SAMS3 is of type II. The properties of the isoenzymes
      were compared after heterologous expression of the individual enzymes, but no
      significant differences were detected in a) optima for temperature (37 to 45
      degrees C) or pH (7 to 8.3); b) dependence on cations (divalent: Mg2+, Mn2+,
      Co2+; monovalent: K+, NH4+, Na+); c) K(m)s for ATP and L-methionine; d)
      inhibition by reaction products (S-adenosyl-L-methionine, PPi, Pi), by the
      reaction intermediate tripolyphosphate, and by the substrate analogues ethionine
      and cycloleucine; e) response to metabolites from the methyl cycle (L
      homocysteine) or from related pathways (L-ornithine, putrescine, spermidine,
      spermine); f) native protein size (gel permeation chromatography). The results
      represent the first characterization of plant SAMS isoenzyme properties with
      individually expressed proteins. The possibility is discussed that the isoenzyme
      differences reflect specificities in the association with enzymes that use S
      adenosyl-L-methionine.

PMID- 9037141
TI  - Isolation, characterization and molecular cloning of the mannose-binding lectins
      from leaves and roots of garlic (Allium sativum L.).
AB  - Two novel lectins were isolated from roots and leaves of garlic. Characterization
      of the purified proteins indicated that the leaf lectin ASAL is a dimer of two
      identical subunits of 12 kDa, which closely resembles the leaf lectins from
      onion, leek and shallot with respect to its molecular structure and agglutination
      activity. In contrast, the root lectin ASARI, which is a dimer of subunits of 15
      kDa, strongly differs from the leaf lectin with respect to its agglutination
      activity. cDNA cloning of the leaf and root lectins revealed that the deduced
      amino acid sequences of ASAL and ASARI are virtually identical. Since both
      lectins have identical N-terminal sequences the larger Mr of the ASARI subunits
      implies that the root lectin has an extra sequence at its C-terminus. These
      results not only demonstrate that virtually identical precursor polypeptides are
      differently processed at their C-terminus in roots and leaves but also indicate
      that differential processing yields mature lectins with strongly different
      biological activities. Further screening of the cDNA library for garlic roots
      also yielded a cDNA clone encoding a protein composed of two tandemly arrayed
      lectin domains. Since the presumed two-domain root lectin has not been isolated
      yet, its possible relationship to the previously described two-domain bulb lectin
      could not be studied at the protein level.

PMID- 9037142
TI  - Characterization of RNA-mediated resistance to tomato spotted wilt virus in
      transgenic tobacco plants expressing NS(M) gene sequences.
AB  - Transgenic Nicotiana tabacum plants expressing RNA sequences of the tomato
      spotted wilt virus NS(M) gene, which encodes the putative viral movement protein,
      were found to be highly resistant to infection with the virus. Expression of
      untranslatable as well as anti-sense RNA of the NS(M) gene resulted in resistance
      levels as high as those in plants expressing translatable RNA sequences. For all
      three types of transgenic plants resistance levels of up to 100% were reached in
      the S2 progeny. These results indicate that the resistance mediated by the NS(M)
      gene is accomplished by expression of transcripts rather than protein in
      transgenic plants, similar to previously observed N gene-mediated resistance.
      Protoplast inoculations revealed that resistant plants expressing NS(M) are, in
      contrast to N transgenic resistant plants, not resistant at the cellular level.
      This suggests the RNA-mediated resistance mechanism against TSWV targets viral
      mRNAs rather than the viral genome.

PMID- 9037143
TI  - A 146 bp fragment of the tobacco Lhcb1*2 promoter confers very-low-fluence, low
      fluence and high-irradiance responses of phytochrome to a minimal CaMV 35S
      promoter.
AB  - The occurrence of very-low-fluence responses (VLFR), low-fluence responses (LFR)
      and high-irradiance responses (HIR) of phytochrome was investigated for the
      expression of the gene of beta-glucuronidase (gusA) under the control of the
      tobacco Lhcb1*2 promoter, in etiolated transgenic tobacco seedlings. The activity
      of beta-glucuronidase (GUS) showed biphasic responses to the calculated
      proportion of Pfr provided by light pulses. The first phase (i.e. the VLFR)
      showed a maximum for Pfr levels characteristic of far-red light. The second phase
      (i.e. the LFR) was observed at higher Pfr levels and was reversible by far-red
      light pulses. The strong effect of continuous far-red light (i.e. HIR) was
      fluence-rate-dependent and could not be replaced either by hourly pulses of the
      same spectral composition and total fluence or by very low fluences of red light.
      Deletion of the Lhcb1*2 promoter to -453 caused little loss of GUS activity. The 
      453 to -31, -270 to -31 and -176 to -31 fragments of the Lhcb1*2 promoter
      conferred proportionally normal VLFR, LFR and HIR to a truncated (-46 to +8) CaMV
      35S minimal promoter. This is the first demonstration of the presence of three
      phytochrome action modes in the control of the transcriptional activity of a
      single gene. The cis-acting regulatory elements necessary for VLFR, LFR and HIR
      are present in a 146 bp fragment of the tobacco Lhcb1*2 promoter.

PMID- 9037144
TI  - The promoter of the tobacco Tnt1 retrotransposon is induced by wounding and by
      abiotic stress.
AB  - The transcription of the tobacco Tnt1 retrotransposon was previously shown to be
      induced, in tobacco and in heterologous species, by microbial elicitors and by
      pathogen infections. We report here that the expression of the Tnt1 promoter is
      also activated in heterologous species such as tomato and Arabidopsis by
      wounding, freezing and by other abiotic factors known to induce the plant defence
      response, such as salicylic acid, CuCl2, or oxidative stress. A similar
      regulation is observed in tobacco for most treatments. The induction of the Tnt1
      promoter expression by wounding remains localized around injury points. In CuCl2
      treated Arabidopsis plants, the transcription of Tnt1 is correlated with
      accumulation of the phytoalexin camalexin and with the expression of the EL13
      defence gene. The interest of the Tnt1 promoter as a sensitive indicator of the
      plant defence responses is discussed.

PMID- 9037145
TI  - Characterization of dynamics of the psbD light-induced transcription in mature
      wheat chloroplasts.
AB  - Dynamical aspects of three chloroplast promoters responding to change in light
      condition were examined in mature chloroplasts of wheat (Triticum aestivum) by in
      vitro transcription. The wheat psbD/C operon has four distinct promoters, two of
      which named as D/C-3 and D/C-4 promoters dominantly function in mature
      chloroplasts to produce the mRNAs encoding D2/CP43 and CP43 alone, respectively.
      Activity of the D/C-3 promoter in mature chloroplasts was reduced to less than
      30% by 24 h dark adaptation and recovered by re-illumination to the original
      level within 30 to 60 min. The activation of the D/C-3 promoter which requires de
      novo cytoplasmic protein synthesis was induced by low fluence of light (e.g. 16
      microE m(-2) s(-1)), but the extent of activation increased with increasing light
      fluence. The accumulation of mRNAs from the D/C-3 promoter saturated at 2- to 3
      fold higher level within 2 h when the dark-adapted seedlings were transferred to
      the light at 72 microE m(-2) s(-1), concomitant with the increase in rate of D2
      synthesis, suggesting that synthesis of D2 in mature chloroplasts is controlled
      via the D/C-3 promoter activity in a light-dependent way. Activity of the D/C-4
      promoter slightly increased in the dark and decreased in the light. Effect of
      light on the psbA promoter activity was not observed at all in mature
      chloroplasts. In vitro transcriptional analysis of the D/C-3 promoter with 5'
      deletion mutations revealed that at least two cis elements which are located
      within the sequences of -78 to -47 and -46 to -29 of the transcription initiation
      site, respectively, act as enhancing elements in the D/C-3 promoter. The light
      switching element of the transcription, however, was suggested to be located in
      the core promoter sequence downstream of the -35 element.

PMID- 9037146
TI  - Characterization of a tobacco extensin gene and regulation of its gene family in
      healthy plants and under various stress conditions.
AB  - A genomic clone (Ext 1.4) encoding an extensin was isolated from a Nicotiana
      tabacum genomic library. The encoded polypeptide showed features characteristic
      of extensins such as Ser-(Pro)4 repeats and a high content in Tyr and Lys
      residues. The presence of one Tyr-Leu-Tyr-Lys motif suggests the possibility for
      one intramolecular isodityrosine cross-link whereas numerous Val-Tyr-Lys motifs
      may participate in intermolecular cross-links. This extensin appears to be close
      to an extensin already characterized in N. tabacum but very different from the
      Ext 1.2 extensin of N. sylvestris. The analysis of genomic DNA gel blots using
      probes spanning different parts of the gene showed that the Ext 1.4 gene belongs
      to a complex multigene family having one member originating from N. sylvestris
      and three members from N. tomentosiformis. The Ext 1.4 specific probe found a 1.4
      kb mRNA in stems, roots, ovaries and germinating seeds of healthy plants. The Ext
      1.4 gene family is strongly induced in actively dividing cell suspension cultures
      and after wounding of leaves or stems in conditions where root formation occurs.
      On the contrary, it is not induced in leaves in response to a hypersensitive
      reaction to a viral infection or after elicitor treatment.

PMID- 9037147
TI  - Cloning and characterization of a pollen-specific cDNA encoding a glutamic-acid
      rich protein (GARP) from potato Solanum berthaultii.
AB  - A pollen-specific cDNA was isolated from a cDNA library of in vitro germinated
      pollen of the diploid potato species Solanum berthaultii. The cDNA clone,
      designated SB401, hybridizes to a messenger RNA of 1.2 kb length in mature and
      germinated pollen. SB401 messenger RNA is absent from other parts of the plant,
      including other flower tissues. SB401 cDNA, which possesses a long stretch of AT
      rich 5'-untranslated leader sequence, encodes a glutamic acid-rich protein (GARP)
      which is hydrophilic throughout and contains six imperfect repeated motifs of the
      sequence V-V-E-K-K-N/E-E with the di-basic amino acid residue pair (K-K) as the
      core within the repeats. These repeats are spaced at irregular intervals and
      predicted to form an alpha-helical structure. The SB401 protein was over
      expressed in Escherichia coli and the purified protein was used for raising
      antiserum. Both E. coli-expressed and the endogenous SB401 proteins in pollen and
      pollen tubes appear much larger on SDS-polyacrylamide gels than their calculated
      molecular masses. Immunoblotting revealed the protein to be most abundant in
      germinated pollen. The structural features of SB401 protein and a possible role
      for the protein in pollen development, pollen germination, and pollen tube growth
      are discussed.

PMID- 9037148
TI  - Molecular cloning and expression of two cDNAs encoding asparagine synthetase in
      soybean.
AB  - Two cDNA clones (SAS1 and SAS2) encoding different isoforms of asparagine
      synthetase (AS; EC 6.3.5.4) were isolated. Their DNA sequences were determined
      and compared. The amino-terminal residues of the predicted SAS1 and SAS2 proteins
      were identical to those of the glutamine binding domain of AS from pea,
      asparagus, Arabidopsis and human, suggesting that SAS1 and SAS2 cDNAs encode the
      glutamine-dependent form of AS. The open reading frames of SAS1 and SAS2 encode a
      protein of 579 and 581 amino acids with predicted molecular weights of 65182 and
      65608 Da respectively. Similarity of the deduced amino acid sequences of SAS1 and
      SAS2 with other known AS sequences were 92% and 93% for pea AS1; 91% and 96% for
      pea AS2; 88% and 91% for asparagus; 88% and 90.5% for Arabidopsis; 70.5% and
      72.5% for E. coli asnB and 61% and 63% for man. A plasmid, pSAS2E, was
      constructed to express the soybean AS protein in Escherichia coli.
      Complementation experiments revealed that the soybean AS protein was functional
      in E. coli. Southern blot analysis indicated that the soybean AS is part of a
      small gene family. AS transcript was expressed in all tissues examined, but
      higher levels were seen in stem and root of light-grown tissue and leaves of dark
      treated tissue.

PMID- 9037149
TI  - Characterization of two cDNA clones for mRNAs expressed during ripening of melon
      (Cucumis melo L.) fruits.
AB  - In vitro translation of mRNAs and polyacrylamide gel electrophoresis of proteins
      from melons revealed that several mRNAs increased in amount during ripening,
      indicating the existence of other ripening genes in addition to those cloned
      previously. To identify ripening-related genes we have screened a ripe melon cDNA
      library and isolated two novel cDNA clones (MEL2 and MEL7) encoding unidentified
      proteins. Southern analysis revealed that MEL2 and MEL7 are encoded by low-copy
      number genes. The MEL2 cDNA clone is near full-length, corresponds to a 1600
      nucleotide mRNA that accumulates during ripening and encodes a predicted protein
      rich in hydrophobic amino acids. The MEL7 cDNA clone is full-length, corresponds
      to a mRNA of 0.7 kb which accumulates during early ripening stages and is also
      present at low levels in other organs of the melon plant. The MEL7 predicted
      polypeptide is 17 kDa and shows significant homology with the major latex protein
      from opium-poppy. Wounding and ethylene treatment of unripe melon fruits 20 days
      after anthesis showed that MEL2 and MEL7 mRNAs are only induced by ethylene.

PMID- 9037151
TI  - Differential transcript induction of parsley pathogenesis-related proteins and of
      a small heat shock protein by ozone and heat shock.
AB  - Parsley (Petroselinum (crispum L.) is known to respond to pathogen attack by the
      synthesis of furanocoumarins and to UV irradiation by the synthesis of flavone
      glycosides whereas ozone treatment results in the induction of both pathways. A
      cDNA library from parsley plants was differentially screened using labelled
      reverse-transcribed poly(A)+ RNA isolated from ozone-treated parsley plants. This
      resulted in the isolation of 13 independent cDNA clones representing ozone
      induced genes and of 11 cDNA clones representing ozone-repressed genes. DNA
      sequencing of several clones resulted in the identification of pathogenesis
      related protein 1-3 (PR1-3), of a new member of PR1 cDNAs (PRI-4) and of a small
      heat shock protein (sHSP). Northern blot analyses showed a transient induction of
      the three mRNA species after ozone fumigation. In contrast, heat shock treatment
      of parsley plants resulted in an increase of sHSP mRNA whereas no increase for
      transcripts of PR1-3 and PR1-4 could be observed. This is the first characterized
      sHSP cDNA clone for plants induced by heat shock, as well as by oxidative stress
      caused by ozone.

PMID- 9037150
TI  - Structure of the parsley caffeoyl-CoA O-methyltransferase gene, harbouring a
      novel elicitor responsive cis-acting element.
AB  - The sequence of the S-adenosyl-L-methionine:trans-caffeoyl-CoA O
      methyltransferase (CCoAOMT, EC2.1.1.104) gene, including the 5'-flanking region
      of 5 kb, was determined from parsley (Petroselinum crispum) plants. The enzyme
      appears to be encoded by one or two genes, and the ORF is arranged in five exons
      spaced by introns from 107 to 263 bp in length. The genomic sequence matches the
      ORF of the cDNA previously reported from elicited parsley cell cultures, showing
      only three base changes that do not affect the enzyme polypeptide sequence. S1
      nuclease protection assays and primer extension analyses with genomic and cDNA
      templates revealed the transcription start site 67 bp upstream of the translation
      start codon, indicating a shorter 5'-UTR than reported previously for the
      transcript. Promoter regulatory consensus elements such as two 'CAAT' boxes and
      one 'TATA' box were identified at -196, -127 and -31, respectively, relative to
      the transcription start site, and an SV 40-like enhancer element is located 347
      bp upstream. Most notably, three putative cis-regulatory elements were recognized
      by sequence alignments, which represent motifs recurring in the promoters of
      several genes of the stress-inducible phenylpropanoid pathway (boxes P, A and L).
      Transient expression assays with a set of 5'-truncated promoter-GUS fusions show
      that significant promoter activity is retained in a 354 bp promoter fragment. In
      vitro DNase 1 footprint experiments and electrophoretic mobilty shift assays
      (EMSA) identified in this fragment a unique sequence motif with elicitor
      inducible trans-factor binding activity, which was unrelated to boxes P, A, or L.
      This novel cis-regulatory element, designated box E, appears to be conserved in
      the TATA-proximal regions of other stress-inducible phenylpropanoid genes, and in
      vitro binding of nuclear protein was confirmed in EMSA assays for such an element
      from the PAL-1 promoter (-54 to -45). Moreover, the deletion of box E reduced the
      activity and erased the elicitor-responsiveness of the CCoAOMT promoter in
      transient expression assays. The results corroborate the proposed physiological
      function of CCoAOMT in elicited plant cells and may shed new light on the
      sequential action of trans-active factors in the regulation of phenylpropanoid
      genes.

PMID- 9037152
TI  - Engineering resistance against tomato yellow leaf curl virus (TYLCV) using
      antisense RNA.
AB  - One of the most severe diseases of cultivated tomato worldwide is caused by
      tomato yellow leaf curl virus (TYLCV), a geminivirus transmitted by the whitefly
      Bemisia tabaci. Here we describe the application of antisense RNAs to interfere
      with the disease caused by TYLCV. The target of the antisense RNA is the rare
      messenger RNA of the Rep protein, encoded by the C1 gene. Transgenic Nicotiana
      benthamiana plants expressing C1 antisense RNA were obtained and shown to resist
      infection by TYLCV. Some of the resistant lines are symptomless, and the
      replication of challenge TYLCV almost completely suppressed. The transgenes
      mediating resistance were shown to be effective through at least two generations
      of progeny.

PMID- 9037153
TI  - Molecular cloning, characterization and expression of cDNA encoding phosphoserine
      aminotransferase involved in phosphorylated pathway of serine biosynthesis from
      spinach.
AB  - Phosphoserine aminotransferase (PSA) catalyzes the conversion of
      phosphohydroxypyruvate to phosphoserine in the phosphorylated pathway of serine
      biosynthesis. A cDNA clone encoding PSA was isolated from the cDNA library of
      spinach (Spinacia oleracea L.) green leaves. Determination of the nucleotide
      sequence revealed the presence of an open reading frame encoding 430 amino acids,
      exhibiting 38-50% homology with the amino acid sequences of bacterial, yeast and
      animal PSA. It contains an N-terminal extension of ca. 60 amino acids in addition
      to the sequences from other organisms. The general features of plastidic transit
      peptide are observed in this N-terminal sequence, suggesting the plastid
      localization of the PSA protein encoded by this cDNA. The bacterial expression of
      the cDNA could functionally rescue the auxotrophy of serine in the serC- mutant,
      Escherichia coli KL282. The enzymatic activity of PSA was demonstrated in vitro
      in the extracts of E. coli over-expressing the cDNA. Southern blot analysis
      indicated the presence of a couple of related genes (Psa) in the spinach genome.
      RNA blot hybridization suggested the preferential expression of the Psa gene in
      the roots of green seedlings and in the suspension cells cultured under a dark
      condition.

PMID- 9037154
TI  - Pollen embryogenesis.

PMID- 9037155
TI  - Comparative analysis of the chromosomal and genomic organization of Ty1-copia
      like retrotransposons in pteridophytes, gymnosperms and angiosperms.
AB  - We have investigated the physical distribution of the reverse transcriptase genes
      of Ty1-copia-like retrotransposable elements from 12 plant species belonging to
      different subdivisions by hybridization in situ on chromosome preparations. Ty1
      copia-like elements showed different and non-random hybridization patterns. A
      dispersed distribution throughout most of the chromosomes with reduced
      hybridization at some regions or with some weak clustering at other regions was
      found in Allium cepa, Beta vulgaris, Brassica campestris, Brassica oleracea,
      Pennisetum glaucum, Pinus elliottii, Selaginella apoda, Vicia faba and Vicia
      narbonensis. Reduced hybridization occurred mainly at centromeric regions,
      nucleolus-organizing regions and regions known to be mainly composed of tandemly
      repeated sequences. In the fern Pteris cretica the retroelements showed a
      dispersed genomic organization with clustering at some chromosomal regions and
      whole chromosomes showing little signal. In Arabidopsis thaliana and Cicer
      arietinum Ty1-copia-like elements were found in clusters at the paracentromeric
      heterochromatin, a novel organization for a repetitive element in A. thaliana.
      New retroelement families were isolated from A. thaliana and from Beta vulgaris.
      Alignment of the deduced peptide sequences with Ty1-copia-like elements from
      other plants showed considerable divergence which was used to calculate their
      relationships, indicating the value of reverse transcriptase gene analysis in
      phylogenetic and biodiversity studies.

PMID- 9037157
TI  - Mitochondrial DNA variations and nuclear RFLPs reflect different genetic
      similarities among 23 Arabidopsis thaliana ecotypes.
AB  - The mitochondrial genome of 23 Arabidopsis thaliana ecotypes was analysed by
      Southern hybridization in total cellular DNA. Firstly, the extent of divergence
      between the mitochondrial genomes in closely related lines of one plant species
      and secondly, the use of mitochondrial versus nuclear RFLPs to determine
      evolutionary relationships between Arabidopsis ecotype isolates was investigated.
      Highly divergent stoichiometries of alternative mitochondrial genome arrangements
      characterize individual ecotypes including the complete loss of a 5 kb region
      from ecotype Landsberg without apparent effect on plant viability. The genetic
      similarities between ecotypes suggested by mitochondrial genome arrangements
      differ from those deduced from 18 nuclear RFLP loci (CAPS markers). Similarity of
      nuclear RFLP patterns among the 23 Arabidopsis ecotypes neither correlates with
      their geographic origin nor with the observed mitochondrial genome arrangements.
      A promiscuous mitochondrial sequence insertion previously identified in ecotype
      Columbia is also found in the nuclear genomes of ecotypes Eifel, Enkheim and
      Hilversum. Two ecotypes (Eifel and Tabor) displaying identical RFLP patterns at
      all 18 nuclear loci show differences in both this sequence transfer and a
      mitochondrial DNA recombination event.

PMID- 9037156
TI  - Sense and antisense transcripts of the maize MuDR regulatory transposon localized
      by in situ hybridization.
AB  - Activity of the Mutator transposons of Zea mays varies in different tissues and
      at different stages of development. In the soma, Mu elements excise at a high
      frequency late in tissue development. In germ cells, Mu elements rarely excise,
      but they amplify and insert at high levels around the time of meiosis. At all
      other times, Mu elements can duplicate and insert at a low frequency. To
      determine whether the patterns of Mutator activity correlate with tissue or cell
      specific transcription of the regulatory transposon MuDR, we used in situ
      hybridization to localize the sense MuDR transcripts, mudrA and mudrB, in
      pistillate florets and embryos of four different maize Mutator stocks. We found
      mudrA and mudrB transcripts uniformly distributed in all tissues of immature,
      meristem-rich florets and in both somatic and germinal tissues of mature florets.
      In mature flowers, transcripts of both genes accumulate to high levels in the
      tapetal (endothelium) layer surrounding the embryo sac. We also found transcripts
      from the antisense strand of the mudrA gene in all cell types in the florets. In
      developing embryos, all MuDR transcripts were present in all tissues. Different
      Mutator stocks had characteristic accumulation patterns that were maintained
      throughout embryo development.

PMID- 9037159
TI  - Seasonal expression of a dehydrin gene in sibling deciduous and evergreen
      genotypes of peach (Prunus persica [L.] Batsch).
AB  - A cDNA library was created from cold-acclimated bark tissue of peach and
      selectively probed using an antibody directed against the lysine-rich consensus
      region of dehydrin proteins. Several clones were thus obtained which had a high
      degree of sequence similarity to other dehydrin genes. Northern analysis, using
      clone 5a, indicated that a 1.8 kb transcript was seasonally expressed in sibling
      deciduous and evergreen genotypes of peach, and also inducible by water deficit
      in cv. Rio Oso Gem. The evergreen and deciduous genotypes differ significantly in
      both their ability to cold-acclimate and in the seasonal expression of the
      dehydrin transcript and protein. In both genotypes, the transcript was maximally
      expressed during winter and undetectable in May-July. The evergreen genotype
      (less cold-tolerant), however, displayed transcript accumulation which lagged
      behind and declined sooner than in the deciduous genotype. Protein expression was
      similar to transcript expression, however, protein expression in the evergreen
      genotype lagged considerably behind transcript accumulation in the fall. This
      indicates that several levels of regulation of dehydrin proteins may exist during
      cold acclimation. A genomic clone (G10a) was isolated which contained the full
      length dehydrin gene, designated ppdhn1. The peach dehydrin gene encodes 472
      amino acids with a predicted size of 50,020 Da. The encoded protein (PCA60)
      contains nine of the lysine-rich repeats characteristic of dehydrins and two
      DEYGNP motifs at the amino acid terminus. A genomic blot, probed with clone 5a
      under stringent conditions, indicated that one or two highly homologous genes are
      present in peach, whereas an additional member was detected under low-stringency
      conditions. It is suggested that several members of the dehydrin gene family may
      exist in peach that vary in their relation to ppdhn1.

PMID- 9037158
TI  - Isolation and characterization of a gene encoding endo-beta-1,4-glucanase from
      pepper (Capsicum annuum L.).
AB  - The endo-beta-1,4-glucanases, or cellulases, of higher plants are cell wall
      associated enzymes believed to function in cell wall changes associated with the
      diverse processes of fruit ripening, organ abscission and cell elongation. We
      have isolated and characterized cDNA and genomic clones encoding a cellulase,
      PCEL1, which is abundant in ripening pepper fruit. Genomic analysis indicates
      that PCEL1 is encoded by a single gene, PCEL1, which belongs to a small,
      structurally divergent gene family. In ripening fruit, PCEL1 transcription is
      initiated at two distinct sites which yields overlapping mRNA species of 1.7 and
      2.1 kb. High-level accumulation of both transcripts occurs in red fruit, while
      the 1.7 kb transcript is detected at a much lower level in stem and petiolar
      tissue. The increase in cellulase activity which is measured during fruit
      ripening is the product of PCEL1 expression and is tightly coupled to fruit
      reddening. High-level applications of ethylene serve to enhance the rate of
      ripening and the accumulation of PCEL1 mRNA. A direct role for ethylene in
      regulating PCEL1 expression is shown by the exclusive induction, in immature
      green fruit, of the 1.7 kb transcript in response to prolonged high-level
      exposure to ethylene--a pattern of expression not observed in fruit development
      on the vine.

PMID- 9037160
TI  - Expression characteristics of OS-ACS1 and OS-ACS2, two members of the 1
      aminocyclopropane-1-carboxylate synthase gene family in rice (Oryza sativa L. cv.
      Habiganj Aman II) during partial submergence.
AB  - Deepwater rice can grow in the regions of Southeast Asia that are flooded during
      the monsoon season because it has several adaptations allowing it to survive
      under flooded conditions. One such adaptation is the ability for rapid internode
      elongation upon partial submergence to maintain its foliage above the rising
      flood water levels. Ethylene is considered to be the trigger of this growth
      response because deepwater conditions not only trap ethylene in submerged organs,
      but also enhance the activity of 1-aminocyclopropane-1-carboxylate (ACC)
      synthase. Herein we have studied the expression characteristics of two members of
      the five-member multigene family encoding ACC synthase in rice OS-ACS1 and OS
      ACS2 and show that partial submergence induces expression of OS-ACS1 and
      suppresses expression of OS-ACS2. The induction of OS-ACS1 occurs within 12 h of
      partial submergence and at low oxygen concentrations. The data also suggest that
      deepwater conditions posttranscriptionally regulate ACC synthase activity. OS
      ACS1 gene expression may contribute to longer-term ethylene production, but not
      to the initial, growth-promoting increase in ethylene synthesis.

PMID- 9037161
TI  - Mutations of cytochrome b6 in Chlamydomonas reinhardtii disclose the functional
      significance for a proline to leucine conversion by petB editing in maize and
      tobacco.
AB  - We have introduced a proline codon in place of a leucine codon at position 204 of
      the petB gene of Chlamydomonas reinhardtii. This gene modification mimics the
      presence of proline codons at the same position in the petB genes of maize and
      tobacco, which are subsequently edited to leucine codons at the RNA level.
      Following transformation, we observed no editing at this position in C.
      reinhardtii, independent of the type of proline codon we have used: the CCA
      codon, edited in maize, or a CCT codon. Strains carrying the introduced mutation
      were non phototrophic and displayed a block in photosynthetic electron transfer,
      consistent with a lack of cytochrome b6f activity. Thus the presence of a proline
      residue at position 204 in cytochrome b6 is detrimental to photosynthesis. We
      show that the mutant phenotype arose from a defective assembly of cytochrome b6f
      complexes and not from altered electron transfer properties in the assembled
      protein complex. Biochemical comparison of the proline-containing transformants
      with a cytochrome b6 mutant deficient in heme-attachment indicates that their
      primary defect is at the level of assembly of apocytochrome b6 with the bh heme,
      thereby preventing assembly of the whole cytochrome b6f complex.

PMID- 9037162
TI  - An endo-1,4-beta-glucanase expressed at high levels in rapidly expanding tissues.
AB  - Plant developmental processes involving modifications to cell wall structure,
      such as cell expansion, organ abscission and fruit ripening, are accompanied by
      increased enzyme activity and mRNA abundance of endo-1,4-beta-glucanases
      (EGases). An EGase cDNA clone, Cel4, isolated from tomato (Lycopersicon
      esculentum) has been shown to be identical to a tomato pistil-predominant EGase
      cDNA, TPP18. In addition to its previously reported expression during certain
      stages of early pistil development, Cel4 mRNA was also detected at high levels in
      the growing zones of etiolated hypocotyls (about 2.5-fold less than in pistils)
      and in young expanding leaves (about 3.5-fold less than in pistils). The
      abundance of Cel4 mRNA declined precipitously in older tissues as cells became
      fully expanded, and was barely detectable in mature vegetative tissues. Cel4 mRNA
      abundance was also low in abscission zones, and did not increase as abscission
      progressed. In fruit, Cel4 mRNA was present at low levels during fruit expansion,
      but was essentially absent during subsequent fruit development and ripening.
      Treatment of etiolated hypocotyls with ethylene or high concentrations of auxin
      sufficient to induce rapid lateral cell expansion and hypocotyl swelling also
      brought about an approximate doubling of Cel4 mRNA abundance, suggesting that
      Cel4 mRNA accumulation may be promoted directly or indirectly by ethylene. Thus,
      accumulation of Cel4 mRNA was found to be correlated with rapid cell expansion in
      pistils, hypocotyls and leaves.

PMID- 9037163
TI  - Molecular characterization and promoter analysis of the maize cytosolic
      glyceraldehyde 3-phosphate dehydrogenase gene family and its expression during
      anoxia.
AB  - Maize cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC) is encoded by a
      small multi-gene family consisting of gpc1, gpc2, gpc3 and gpc4. GAPC3/4 protein
      is synthesized in roots during anoxic conditions and is known to be one of the
      'anaerobic polypeptides'. We further analyzed the gpc gene family by isolating
      full-length cDNA clones of gpc2, gpc3, gpc4 and genomic clones of gpc2 and gpc4.
      The deduced amino acid sequence of GAPC4 has 99.4% identity with that of GAPC3 as
      compared to only 81% with either GAPC1 or GAPC2 amino acid sequence. Based on the
      deduced amino acid sequence identity we designated GAPC1 and GAPC2 as group I
      (97% identical) and GAPC3 and GAPC4 as group II (99.4% identical). As previously
      reported for gpc3, transcript levels were also induced for gpc4 by anaerobiosis.
      Neither heat shock, cold nor salt stress induced the expression of gpc3 or gpc4.
      In contrast, the transcript accumulation of gpc1 and gpc2 either remained
      constitutive or decreased in response to anoxia. The upstream regions of gpc2 and
      gpc4 contain typical eukaryotic promoter features with transcription start points
      at 76 and 68 bp upstream of their respective translation initiation sites.
      Transient expression analysis of gpc4 promoter-beta-glucuronidase (GUS) reporter
      gene constructs in bombarded maize suspension culture cells was used to examine
      the role of 5'-flanking sequence of gpc4. The gpc4 promoter (-1997 to +39 bp) was
      sufficient to induce GUS activity approximately three-fold in response to
      anaerobiosis. 5'-unidirectional deletion analysis revealed that the critical
      region of gpc4 required for its induced expression lies between -290 and -157.
      This region has reverse-oriented putative 'anaerobic response elements', G-box
      like sequences, and a GC motif similar to that previously defined as a regulatory
      element of maize adh1 and Arabidopsis adh, as well as the sequences found in
      other environmentally inducible genes. The relevance of these elements in
      conferring anaerobic induction of gpc4 gene expression is discussed.

PMID- 9037164
TI  - The temporal and spatial transcription pattern in root nodules of Vicia faba
      nodulin genes encoding glycine-rich proteins.
AB  - Four different transcript sequences encoding gene products with an unusually high
      glycine content were identified in Vicia faba root nodules. Northern blot
      analysis revealed a strong nodule specific expression of the corresponding genes.
      Time course experiments showed that two of these genes were transcribed before
      the onset of leghemoglobin expression and hence were designated VfENOD-GRP2 and
      VfENOD-GRP5, whereas the first detection of VfNOD-GRP1 and VfNOD-GRP4 transcripts
      coincided with the appearance of leghemoglobin transcripts in V. faba root
      nodules. A characteristic feature of all encoded nodulins was a hydrophobic N
      terminus, which in the case of the nodulins ENOD-GRP2 and ENOD-GRP5 has the
      characteristics of a signal peptide. Such a structure is comparable to other
      plant glycine-rich proteins decribed as components of the plant cell wall. Based
      on tissue print hybridizations, we found that VfNOD-GRP1, VfENOD-GRP2 and VfNOD
      GRP4 were expressed in the interzone II-III and in the whole nitrogen-fixing zone
      III. In contrast to VfENOD-GRP2 and VfNOD-GRP4, the signal intensity of
      hybridizing VfNOD-GRP1 transcripts was slightly reduced in the more proximal part
      of broad bean root nodules. Apart from the interzone II-III and the nitrogen
      fixing zone III, VfENOD-GRP5 RNA was also detected in large areas of the
      prefixing zone II.

PMID- 9037165
TI  - The Arabidopsis ACT11 actin gene is strongly expressed in tissues of the emerging
      inflorescence, pollen, and developing ovules.
AB  - ACT11 represents a unique and ancient actin subclass in the complex Arabidopsis
      actin gene family. We have isolated and characterized the Arabidopsis ACT11 actin
      gene and examined its expression. Southern blotting with a 5' gene-specific probe
      showed that ACT11 was a single-copy gene in the genome. Northern analysis with a
      3' gene-specific probe and reverse transcriptase-mediated PCR (RT-PCR) using gene
      specific primers detected ACT11 mRNA at low levels in seedling, root, leaf, and
      silique tissue; at moderate levels in the inflorescence stem and flower; and at
      very high levels in pollen. The 5' region of the ACT11 gene, including the
      promoter region, the 5'-untranslated leader, the intron within the leader, and
      the first 19 actin codons, was fused to a beta-glucuronidase (GUS) reporter gene.
      The expression of the ACT11/GUS fusion was examined histochemically in numerous
      independent transgenic Arabidopsis plants. Strong ACT11/GUS activity was detected
      in rapidly elongating tissues and organs (e.g., etiolated hypocotyls, expanding
      leaves, stems) and in floral organ primordia. As the floral buds developed into
      mature flowers, strong GUS activity was gradually restricted to mature pollen and
      developing ovules. ACT11 appears to be the only Arabidopsis actin gene expressed
      at significant levels in ovule, embryo, and endosperm. The unique expression
      patterns in reproductive organs and the sequence divergence of the ACT11 actin
      gene suggest that the ACT11 isovariant plays distinct and required roles during
      Arabidopsis development.

PMID- 9037167
TI  - LhcaR1 of the red alga Porphyridium cruentum encodes a polypeptide of the LHCI
      complex with seven potential chlorophyll a-binding residues that are conserved in
      most LHCs.
AB  - The accessory light-harvesting polypeptides associated with photosystem I (LHCI)
      in Porphyridium cruentum bind chlorophyll a, zeaxanthin and beta-carotene. A cDNA
      library of P. cruentum was screened with an antiserum specific to the LHCI
      polypeptides, and an 0.9 kb fragment was identified as coding for an LHCI
      polypeptide. This cDNA, which we named LhcaR1, has an open reading frame encoding
      222 amino acid residues including a putative transit peptide of 28 amino acids.
      Hydropathy analysis suggests that there are three transmembrane helices in the
      mature polypeptide. Each of the amino acid residues that bind chlorophyll (six
      residues) and serve in stabilizing the helices in higher-plant LHCs are conserved
      in helices 1 and 3 of P. cruentum LhcaR1. The N-terminal flanking regions of
      these two helices also show high sequence conservation with other LHCs. Helix 2
      contains a seventh putative chlorophyll-binding site, but resembles helix 2 of
      higher-plant LHCs to a lesser degree. A sequence motif of 11 residues found near
      the N-terminus and in each of the three helices suggests the possibility that the
      red algal LhcaR1 derives from a gene duplication. Polypeptides of the expected
      molecular weight in six other red algae (Achrochaetium, Bangia, Callithamnion,
      Cyanidium, Polysiphonia, Spermothamnion) were recognized by the antiserum to P.
      cruentum LHCI, indicating a wide distribution of LHCI in rhodophytes.

PMID- 9037166
TI  - cDNA cloning and differential gene expression of three catalases in pumpkin.
AB  - Three cDNA clones (cat1, cat2, cat3) for catalase (EC 1.11.1.6) were isolated
      from a cDNA library of pumpkin (Cucurbita sp.) cotyledons. In northern blotting
      using the cDNA-specific probe, the cat1 mRNA levels were high in seeds and early
      seedlings of pumpkin. The expression pattern of cat1 was similar to that of
      malate synthase, a characteristic enzyme of glyoxysomes. These data suggest that
      cat1 might encode a catalase associated with glyoxysomal functions. Furthermore,
      immunocytochemical analysis using cat1-specific anti-peptide antibody directly
      showed that cat1 encoding catalase is located in glyoxysomes. The cat2 mRNA was
      present at high levels in green cotyledons, mature leaf, stem and green hypocotyl
      of light-grown pumpkin plant, and correlated with chlorophyll content in the
      tissues. The tissue-specific expression of cat2 had a strong resemblance to that
      of glycolate oxidase, a characteristic enzyme of leaf peroxisomes. During
      germination of pumpkin seeds, cat2 mRNA levels increased in response to light,
      although the increase in cat2 mRNA by light was less than that of glycolate
      oxidase. cat3 mRNA was abundant in green cotyledons, etiolated cotyledons, green
      hypocotyl and root, but not in young leaf. cat3 mRNA expression was not dependent
      on light, but was constitutive in mature tissues. Interestingly, cat1 mRNA levels
      increased during senescence of pumpkin cotyledons, whereas cat2 and cat3 mRNAs
      disappeared during senescence, suggesting that cat1 encoding catalase may be
      involved in the senescence process. Thus, in pumpkin, three catalase genes are
      differentially regulated and may exhibit different functions.

PMID- 9037169
TI  - A 38 bp repeat sequence within the pea seed storage protein promoter of legA is a
      binding site for a nuclear DNA-binding protein.
AB  - This paper describes a target sequence for a pea seed nuclear DNA-binding protein
      (of Pisum sativum) present at the cell expansion phase. Electromobility shift
      assays as well as in situ copper-phenanthroline footprinting have shown that this
      protein binds to an imperfect repeat sequence of the legA promoter located -404
      tot -367 relative to the transcriptional start site, a region designated USR1 (
      549 tot -316). Competition assays showed that the same or a related protein binds
      to USR2 located at -833 to -582. Another protein that does not recognize the
      repeat sequence as a target site binds adjacent but upstream to the repeat
      sequence in USR1. It is suggested that these protein-DNA interactions are initial
      events in the assembly of a transcriptional activation complex.

PMID- 9037168
TI  - Cloning and expression analysis of a gene that shows developmental regulation
      upon tuberization in potato.
AB  - Differential screening of a potato leaf cDNA library with cDNA probes made from
      tuberizing and non-tuberizing Solanum demissum plants led to the identification
      of a clone that is upregulated in leaves and other tissues upon tuberization.
      This clone was also shown to have a high level of expression in green tomato
      fruit, its expression falling off as the fruit turns red. No sucrose or hormonal
      regulation of the expression of this clone was observed and it did not respond to
      wounding or heat stress. Clone 32B is 532 bp long and contains an open reading
      frame encoding a small protein of 98 amino acids. The deduced protein sequence
      has a putative signal peptide for ER transport and a 10 amino acid domain in the
      C-terminal region of the protein, both of which are also found in the cotton
      LEA5, Arabidopsis Di21 and the mungbean Arg2 proteins.

PMID- 9037170
TI  - Chloroplastic isoforms of DnaJ and GrpE in pea.
AB  - The folding and assembly of proteins in cells often requires the assistance of
      molecular chaperones such as the Hsp70 and Hsp60 heat shock proteins. Hsp70
      chaperones cooperate with DnaJ and GrpE homologues to ensure a productive folding
      cycle. In this study we describe the gene for the first chloroplast localized
      DnaJ homologue and present evidence that the gene product is at least partially
      associated with the inner envelope membrane. Immunoblot analysis also provides
      evidence for the presence of a GrpE homologue in plastids.

PMID- 9037172
TI  - Characterization of three anther-specific genes isolated from Chinese cabbage.
AB  - Two cDNA libraries were constructed from poly(A)+ RNAs isolated from each of
      immature flowers (less than 2.0 mm long buds) and anthers (2.0-5.0 mm long buds)
      of Chinese cabbage (Brassica campestris L. ssp. pekinensis). Using dot
      differential hybridization, three cDNA clones, designated BIF38, BAN54, and
      BAN237, have been isolated from the constructed cDNA libraries and sequenced
      completely in both directions. Northern blot analyses indicate that all three
      cDNA clones are abundantly expressed in anther, but not in leaf or other floral
      organs. The deduced amino acid sequences of BIF38, BAN54, and BAN237 showed high
      identity with those of known anther-specific genes. Especially the deduced amino
      acid sequence of BIF38 has 98% identity with that of a phospholipid protein gene
      (E2) from Brassica napus. Also, the deduced amino acid sequences of BAN54 and
      BAN237 are similar to the sequences of microspore-specific genes (Bp4A and Bp4C)
      and pollen oleosins (13, pol3 and C98), respectively. Southern blot analyses
      revealed that all three genes belong to multiple gene families in the Chinese
      cabbage genome.

PMID- 9037171
TI  - Aspartic proteinase genes in the Brassicaceae Arabidopsis thaliana and Brassica
      napus.
AB  - Active aspartic proteinase is isolated from Brassica napus seeds and the peptide
      sequence is used to generate primers for PCR. We present here cDNA and genomic
      clones for aspartic proteinases from the closely related Brassicaceae Arabidopsis
      thaliana and Brassica napus. The Arabidopsis cDNA represents a single gene, while
      Brassica has at least 4 genes. Like other plant aspartic proteases, the two
      Brassicaceae enzymes contain an extra protein domain of about 100 amino acids
      relative to the mammalian forms. The intron/exon arrangement in the Brassica
      genomic clone is significantly different from that in mammalian genes. As the
      proteinase is isolated from seeds, the same tissue where 2S albumins are
      processed, this implies expression of one of the aspartic proteinase genes there.

PMID- 9037173
TI  - The interaction between Alzheimer amyloid beta(1-40) peptide and ganglioside GM1
      containing membranes.
AB  - The interaction between Alzheimer amyloid peptide A beta(1-40) and membrane
      lipids was studied by circular dichroism spectroscopy under the conditions of
      physiologically relevant ionic strength and neutral pH. The peptide binds to the
      membranes containing ganglioside GM1 and upon binding undergoes a conformational
      transition from random coil to an ordered structure rich in beta-sheet. This
      interaction appears to be ganglioside-specific as no changes in A beta(1-40)
      conformation were found in the presence of various phospholipids or
      sphingomyelin. The isolated oligosaccharide moiety of the ganglioside was
      ineffective in inducing alterations in the secondary structure of A beta(1-40).
      No interaction was observed between ganglioside GM1 and the N-terminal peptide
      fragment A beta(1-28). Binding to the ganglioside is likely to modulate the
      neurotoxic and/or amyloidogenic properties of A beta(1-40).

PMID- 9037174
TI  - Identification of a novel angiotensin-I-converting enzyme inhibitory peptide
      corresponding to a tryptic fragment of bovine beta-lactoglobulin.
AB  - The angiotensin-I-converting enzyme (ACE) inhibitory activity of a tryptic digest
      of bovine beta-lactoglobulin (beta-lg) was investigated. Intact beta-lg
      essentially did not inhibit ACE while the tryptic digest gave an 84.3% inhibition
      of ACE. Peptide material eluting between 20 and 25% acetonitrile during C18 solid
      phase extraction of the beta-lg tryptic digest inhibited ACE by 93.6%. This solid
      phase extraction fraction was shown by mass spectroscopy to contain beta-lg f(142
      148). This peptide had an ACE IC50 value of 42.6 micromol/l. The peptide was
      resistant to further digestion with pepsin and was hydrolysed to a very low
      extent with chymotrypsin. The contribution of specific amino acid residues within
      the peptide to ACE inhibitory activity and the potential application of this
      peptide as a nutraceutical is discussed.

PMID- 9037175
TI  - Non-thermal effects of microwaves on proteins: thermophilic enzymes as model
      system.
AB  - Two thermophilic and thermostable enzymes, isolated from Sulfolobus solfataricus,
      S-adenosylhomocysteine hydrolase and 5'-methylthioadenosine phosphorylase, were
      exposed to 10.4 GHz microwave radiation in order to discriminate between thermal
      and non-thermal microwave effects. The exposure causes a non-thermal,
      irreversible and time-dependent inactivation of both enzymes; the inactivation
      rate is related to the energy absorbed and is independent of the enzyme
      concentration. The influence of salts on enzyme inactivation has also been
      investigated. Conformational changes of S-adenosylhomocysteine hydrolase,
      detected by fluorescence and circular dichroism techniques, suggest that
      microwaves induce protein structural rearrangements not related to temperature.

PMID- 9037176
TI  - Liposome-mediated DNA vaccination.
AB  - Numerous reports have indicated that intramuscular injection of antigen-coding
      naked plasmid DNA can trigger humoral and cell-mediated protective immunity
      against infection. This follows DNA uptake by muscle fibres, leading to the
      expression and extracellular release of the antigen. Here it is shown for the
      first time that intramuscular immunization of mice with pRc/CMV HBS (encoding the
      S region of hepatitis B antigen; HBsAg) entrapped into positively charged
      (cationic) liposomes leads to greatly improved humoral and cell-mediated
      immunity. These cationic liposome-entrapped DNA vaccines generate titres of anti
      HBsAg IgG1 antibody isotype in excess of 100-fold higher and increased levels of
      both IFN-gamma and IL-4 when compared with naked DNA or DNA complexed with
      preformed similar (cationic) liposomes. It is likely that immunization with
      liposome-entrapped plasmid DNA involves antigen-presenting cells locally or in
      the regional draining lymph nodes.

PMID- 9037177
TI  - Activation of MMP-9 by neutrophil elastase in an in vivo model of acute lung
      injury.
AB  - The effect of neutrophil elastase on the functional status of gelatinases was
      studied in an hamster model developed by intratracheal administration of
      lipopolysaccharide followed by in situ cell activation with phorbol myristate
      acetate. This resulted in the production in bronchoalveolar lavage fluids, in
      addition to the matrix metalloproteinase MMP-9, of a 75 kDa gelatinase associated
      with collagenolytic activity. Treatment in vivo with an elastase inhibitor
      abolished the latter activity. Since, in addition, elastase activates in vitro
      purified MMP-9 gelatinase into a similar 75 kDa entity, these data suggest that
      elastase may be a physiological activator of MMP-9 in vivo.

PMID- 9037178
TI  - 19F-NMR studies of retinol transfer between cellular retinol binding proteins and
      phospholipid vesicles.
AB  - The cellular retinol binding proteins, CRBP and CRBP II, are implicated in the
      cellular uptake of retinol and intracellular trafficking of retinol between sites
      of metabolic processing. 19F-NMR studies of retinol transfer between CRBP and
      CRBP II and phospholipid vesicles, using either fluorine-labeled ligand or
      protein, demonstrated that there was significantly more transfer of retinol from
      CRBP II to lipid vesicles than from CRBP. Differences in how readily protein
      bound retinol is released to lipid bilayers may lead to differences in how these
      two proteins modulate intracellular retinol metabolism.

PMID- 9037179
TI  - The protein kinase C inhibitors Ro 318220 and GF 109203X are equally potent
      inhibitors of MAPKAP kinase-1beta (Rsk-2) and p70 S6 kinase.
AB  - The protein kinase C (PKC) inhibitors Ro 318220 and GF 109203X have been used in
      over 350 published studies to investigate the physiological roles of PKC. Here we
      demonstrate that these inhibitors are not selective for PKC isoforms as was
      previously assumed. Ro 318220 inhibited MAPKAP kinase-1beta (also known as Rsk-2)
      in vitro (IC50 3nM) more potently than it inhibited mixed PKC isoforms (IC50 5
      nM), and it also inhibited p70 S6 kinase (IC50 15 nM). GF 109203X also potently
      inhibited MAPKAP kinase-1beta (IC50 50 nM) and p70 S6 kinase (IC50 100 nM) with
      similar potency to PKC isoforms (IC50 30 nM). The inhibition of MAPKAP kinase
      1beta, p70 S6 kinase, and probably other protein kinases, may explain many of the
      effects previously attributed to PKC.

PMID- 9037180
TI  - Expression, purification and characterization of recombinant human proinsulin.
AB  - We have recently developed a method to produce native human proinsulin using a
      bacterial expression system. A proinsulin fusion protein was recovered from
      inclusion bodies and cleaved using cyanogen bromide. The released proinsulin
      polypeptide was S-sulfonated and purified by anion exchange chromatography.
      Following refolding, proinsulin was purified by reversed-phase high-performance
      liquid chromatography. Combined peptide mapping and mass spectrometric analysis
      indicated that the proinsulin contained the correct disulfide bridging pattern.
      This proinsulin will be used to study the specificity of the furin/PC family of
      converting enzymes by using it as a substrate in a recently developed assay.

PMID- 9037181
TI  - Mapping of a potent transcriptional repression region of the human homeodomain
      protein EVX1.
AB  - The human homeodomain protein EVX1 is a transcriptional repressor in transfected
      mammalian cells and this function depends on a region carboxyl-terminal to the
      homeodomain. In this study, we transiently expressed several deletions of the
      EVX1 C-terminal region in mammalian cells and investigated their effect on the
      transcription of a reporter gene directed by different promoters. We show that
      the repressor activity maps to a region of 51 amino acids with a high abundance
      of alanine and proline residues. This region is able to transfer the repressor
      function to either the entire HOXC6 or CREB transcription factors, or to the GAL4
      DNA binding domain.

PMID- 9037182
TI  - Characterization of dominant lethal mutations in the yeast plasma membrane H+
      ATPase gene.
AB  - Site-directed mutants of yeast ATPase were studied after introduction of mutant
      alleles into a yeast strain where these alleles were constitutively expressed and
      the expression of the wild-type chromosomal ATPase gene was turned off. One
      objection to this constitutive expression system was made apparent recently, as
      dominant lethal mutations are lost by gene conversion with the wild-type allele
      during the process. Here, the phenotypes of the mutant alleles, which were
      studied in a constitutive expression system, are re-evaluated under conditions in
      which these site-directed mutants are conditionally expressed. We show that 12 of
      25 site-directed mutations previously described are actually dominant lethal
      alleles. In addition, we show that dominant mutant proteins interfere with
      transport of wild-type ATPase to the plasma membrane.

PMID- 9037183
TI  - Identification of sds22 as an inhibitory subunit of protein phosphatase-1 in rat
      liver nuclei.
AB  - sds22 was originally identified in yeast as a regulator of protein phosphatase-1
      that is essential for the completion of mitosis. We show here that a structurally
      related mammalian polypeptide (41.6 kDa) is part of a 260-kDa species of protein
      phosphatase-1. This holoenzyme, designated PP-1N(sds22), could be
      immunoprecipitated with sds22 antibodies and was retained by microcystin
      Sepharose. PP-1N(sds22) is a latent phosphatase, but its activity could be
      revealed by the proteolytic destruction of the noncatalytic subunit(s). PP
      1N(sds22) accounted for only 5-10% of the total activity of PP-1 in rat liver
      nuclear extracts. A synthetic 22-mer peptide, corresponding to a leucine-rich
      repeat of sds22, specifically inhibited the catalytic subunit of PP-1, showing
      that at least part of the latency stems from the interaction of the sds22
      repeat(s) with PP-1C.

PMID- 9037184
TI  - Molecular cloning of ERp29, a novel and widely expressed resident of the
      endoplasmic reticulum.
AB  - We have isolated a full-length cDNA clone for a novel 29 kDa protein that is
      highly expressed in rat enamel cells. The clone encodes a 259-residue protein,
      here named ERp29, with structural features (signal peptide and a variant
      endoplasmic reticulum-retention motif, KEEL) that indicate it is a
      reticuloplasmin. ERp29 has limited homology with protein disulfide isomerase and
      its cognates, but lacks their characteristic thioredoxin-like catalytic moiety
      and calcium-binding motifs. ERp29 mRNA was expressed in all rat tissues tested,
      and a homologous transcript was detected in other animal livers (primate,
      ruminant, marsupial). In human hepatoma cells, ERp29 mRNA expression was not
      increased by stresses (tunicamycin, calcium ionophore) that induced other
      reticuloplasmins. We conclude that ERp29 is a new, highly conserved member of the
      reticuloplasmin family which is widely expressed. The apparent lack of both
      calcium binding properties and stress responsiveness distinguish ERp29 from all
      major reticuloplasmins characterised to dates.

PMID- 9037186
TI  - The influence of aspartate 26 on the tautomeric forms of folate bound to
      Lactobacillus casei dihydrofolate reductase.
AB  - The ternary complex of Lactobacillus casei dihydrofolate reductase (DHFR) with
      folate and NADP+ exists as a mixture of three interconverting forms (I, IIa and
      IIb) whose relative populations are pH dependent, with an effective pK of approx.
      6. To investigate the role of Asp26 in this pH dependence we have measured the
      13C chemical shifts of [2,4a,7,9-(13)C4]folate in its complex with the mutant
      DHFR Asp26 --> Asn and NADP+. Only a single form of the complex is detected and
      this has the characteristics of form I, an enol form with its N1 unprotonated. A
      study of the pH dependence of the 13C chemical shifts of DHFR selectively
      labelled with [4-(13)C]aspartic acid in its complex with folate and NADP+
      indicates that no Asp residue has a pK value greater than 5.4. Two of the Asp CO2
      signals appear as non-integral signals with chemical shifts typical of non
      ionised COOH groups and with a pH dependence characteristic of the slow exchange
      equilibria previously characterised for signals in forms I and IIb (or IIa). It
      is proposed that the protonation/deprotonation controlling the equilibria
      involves the O4 position of the folate and that Asp26 influences this indirectly
      by binding in its CO2 form to the protonated N1 group of folate in forms I and
      IIa thus reducing the pK involving protonation at the O4 position to approx. 6.
      These findings indicate that, in forms I and IIa of the ternary complex, folate
      binds to DHFR in a very similar way to methotrexate.

PMID- 9037185
TI  - A single point mutation (E166Q) prevents dicyclohexylcarbodiimide binding to the
      photosystem II subunit CP29.
AB  - Energy-dependent quenching of chlorophyll fluorescence (qE) reflects the action
      of a powerful mechanism of protection from photoinhibition in which the low pH in
      the chloroplast lumen induces dissipation of excess excitation energy.
      Dicyclohexylcarbodiimide (DCCD), a protein-modifying agent, is a powerful
      inhibitor of qE and has been shown to react with acidic residues, in a
      hydrophobic environment, involved in proton translocation. The CP29 subunit of
      photosystem II has been proposed to be the site of qE quenching and shown to bind
      DCCD. We have hypothesised, on the basis of the CP29 protein sequence and of the
      structure of light-harvesting complex II protein, that glutamic acid 166 is the
      DCCD binding site. In this study, we have produced recombinant proteins either
      with wild-type sequence or carrying a mutation on the 166 position. We show that
      the mutant protein does not bind DCCD. This identifies E166 as the site whose
      protonation may lead to a conformational change triggering qE.

PMID- 9037187
TI  - Murine epidermal lipoxygenase (Aloxe) encodes a 12-lipoxygenase isoform.
AB  - Using a combination of conventional screening procedures and polymerase chain
      reaction cloning, we have isolated a cDNA encoding an epidermis-type 12
      lipoxygenase (e12-lipoxygenase) from mouse epidermis. The open reading frame
      corresponds to a protein of 662 amino acids and was found to be 99.8% identical
      to the ORF of an epidermal lipoxygenase gene Aloxe, described recently [Van Dijk
      et al. (1995) Biochim. Biophys. Acta 1259, 4-8]. When expressed in human
      embryonic kidney cells the recombinant protein could be shown to synthesize 12(S)
      HETE from arachidonic acid. By fluorescence in situ hybridization the e12
      lipoxygenase gene was localized to chromosome band 11 B1-B3.

PMID- 9037188
TI  - Molecular cloning and immunological characterisation of Cyn d 7, a novel calcium
      binding allergen from Bermuda grass pollen.
AB  - A cDNA coding for a newly identified Bermuda grass pollen allergen, Cyn d 7, with
      significant sequence similarity to Ca2+-binding proteins, was isolated from a
      cDNA expression library using serum IgE from an allergic individual. The deduced
      amino acid sequence of Cyn d 7 contained two typical Ca2+-binding sites (EF hand
      domains). Depletion of Ca2+ with EGTA led to a loss of IgE-binding capacity of
      rCyn d 7. A synthetic peptide based on domain II showed high IgE reactivity. Cyn
      d 7 therefore represents a grass pollen allergen that belongs to a novel class of
      Ca2+-binding proteins.

PMID- 9037189
TI  - Z,E isomerization of the alpha-84 phycoviolobilin chromophore of
      phycoerythrocyanin from Mastigocladus laminosus investigated by Fourier-transform
      infrared difference spectroscopy.
AB  - The photoreaction of the phycoviolobilin (PVB) chromophore-containing part of
      phycoerythrocyanin (PEC) from Mastigocladus laminosus was investigated by Fourier
      transform infrared spectroscopy (FT-IR). Difference spectra between the parent
      states P566 and P507 were obtained in 1H2O and 2H2O for the first time. The
      spectra are generally characterised by large changes in the range between 1710
      and 1590 cm(-1) and by a strong difference band around 1270 cm(-1). In order to
      study the influence on the PVB chromophore upon aggregation, spectra of the alpha
      subunit and the (alphabeta)3 trimer are compared, showing distinct differences
      which may be of relevance for the chromophore-protein and protein-protein
      interactions. The difference spectra demonstrate many similarities to the spectra
      recently obtained for the Pr --> meta-Rc transition of phytochrome [Foerstendorf
      et al. (1996) Biochemistry 35, 10793-10799]. In particular, a band around 1710
      cm(-1), which was tentatively assigned to the C = O stretch of ring D is also
      observed in the spectra of PEC. It strongly supports this identification and the
      deduced molecular interpretation on the protonation state of the chromophore.

PMID- 9037190
TI  - Insertion of foreign random sequences of 120 amino acid residues into an active
      enzyme.
AB  - Random sequences of 120-130 amino acid residues were inserted into a surface loop
      region of Escherichia coli RNase HI. This library was screened and about 10% of
      the clones were found to retain RNase H activity. Subsequent random mutagenesis
      led to an increase in RNase H activity and solubility of the protein. The
      inserted regions were found not to contribute to the secondary structure of the
      mutant protein. The high frequency of insertion of flexible sequences and the
      increase in the protein's function by further mutagenesis simulate one of the
      events in protein evolution.

PMID- 9037191
TI  - Proteolytic activation of the precursor of membrane type 1 matrix
      metalloproteinase by human plasmin. A possible cell surface activator.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) was suggested to play a
      critical role in the regulation of tissue invasion by normal and neoplastic cells
      by directly mediating the activation of pro-gelatinase A. Recently, the
      proteolytic activation of a pro-MT1-MMP by an intracellular proprotein
      convertase, furin, was reported. In this study, we found that plasmin efficiently
      activates the pro-MT1-MMP by cleaving immediately downstream of Arg108 and Arg111
      in the multi-basic motif between its pro- and catalytic domains that participates
      in the activation of pro-gelatinase A. Our present data suggest that pro-MT1-MMP
      transported to the plasma membrane is activated by plasmin extracellularly and
      thus it may play an important role in the matrix degradation process.

PMID- 9037192
TI  - Regulation of leptin receptor and NPY gene expression in hypothalamus of leptin
      treated obese (ob/ob) and cold-exposed lean mice.
AB  - Leptin receptor gene expression has been measured in arcuate and ventromedial
      hypothalamic nuclei. Receptor mRNA in both hypothalamic areas was higher in obese
      mice than in lean littermates. Twice daily leptin administration for 7 days
      profoundly affected food intake, reduced leptin receptor mRNA in the arcuate
      nucleus, and had a similar effect on neuropeptide Y gene expression. A single
      leptin injection was ineffective. Exposure of lean mice to cold for 24 h caused
      an induction of leptin receptor and NPY mRNA which was normalized when animals
      were returned to the warm. Regulation of receptor gene expression may be an
      important component in the reading of the leptin signal.

PMID- 9037193
TI  - Heterogeneous halothane binding in the SR Ca2+-ATPase.
AB  - The activity of various Ca2+-ATPases is affected by volatile anesthetics, such as
      halothane, commonly used in clinical practice. The effect on the enzyme in
      skeletal muscle sarcoplasmic reticulum (SR) is biphasic, including stimulation at
      clinical anesthetic concentrations and subsequent inhibition at higher
      concentrations. We have previously proposed that the action of a volatile
      anesthetic on Ca2+-ATPases results from its binding in the interior of the enzyme
      molecule [Lopez, M.M. and Kosk-Kosicka, D. (1995) J. Biol. Chem. 270, 28239
      28245]. Presently, we investigated whether the anesthetic interacts directly with
      the skeletal muscle SR Ca2+-ATPase (SERCA1) as evidenced by binding.
      Photoaffinity labeling with [14C]halothane demonstrated that the anesthetic binds
      saturably to SR membranes, and that approximately 80% of the binding is specific,
      with a KI of 0.6 mM. The KI value agrees well with the concentration at which
      halothane half-maximally activates SERCA1. SDS gel electrophoresis of labeled
      membranes indicates that 38-56% of [14C]halothane incorporates into SERCA1, and
      38-53% in lipids. Distribution of label among the three fragments produced by
      controlled tryptic digestion of SERCA1 suggests heterogeneous halothane binding
      presumably in discrete sites in the enzyme. The results provide the first direct
      evidence that halothane binds to SERCA1. Potentially this binding could be
      related to anesthetic effect on enzyme's function.

PMID- 9037194
TI  - Partial coverage of phospholipid model membranes with annexin V may completely
      inhibit their degradation by phospholipase A2.
AB  - Phospholipase A2 (PLA2)-mediated hydrolysis of membrane phospholipids was
      measured by ellipsometry, and the inhibition of this process by annexin V was
      studied. Planar membranes, consisting of phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylserine (PC/PE/PS; 54:33:13, on molar
      basis), were degraded by pancreatic PLA2, and the rate of hydrolysis was limited
      to about 0.7%/min. The influence of graded coverage of the membrane with annexin
      V was studied. The degree of PLA2 inhibition was nonlinearly related to the
      amount of membrane-bound annexin V, and binding of only 12% and 54% of full
      membrane coverage resulted in, respectively, 50% and 93% inhibition. These
      findings indicate that the inhibition of PLA2-mediated hydrolysis by annexin V
      cannot be simply explained by shielding of phospholipid substrates from the
      enzyme. Moreover, the present results leave room for a role of endogenous annexin
      V in regulating phospholipid turnover in the plasma membrane of parenchymal cells
      such as cardiomyocytes.

PMID- 9037195
TI  - Down-regulation of LH/hCG receptor in rat cultured granulosa cells.
AB  - Initial experiments established the experimental conditions necessary for the
      induction of LH receptor mRNA down-regulation in granulosa cells isolated from
      diethylstilbestrol (DES)-primed immature rats. LH/hCG receptor mRNA was first
      induced in granulosa cells by incubating them for 24 h with FSH. Exposure of
      granulosa cells to a second dose of gonadotropin caused a decrease in LH/hCG
      receptor mRNA and binding levels after 4 h. This effect was transient, by 12 h
      the mRNA levels had returned to control levels, and by 24 h the mRNA levels were
      higher than the control. To evaluate the ability of cAMP to down-regulate the
      receptor, cells were exposed to 8-Br-cAMP. The pattern of sustained decrease in
      LH/hCG receptor mRNA levels seen with 8-Br-cAMP was similar to that with
      gonadotropins. The presence of activin with FSH or hCG is more effective than FSH
      or hCG alone in inducing LH/hCG receptor down-regulation in rat granulosa cells.
      The LH/hCG receptor mRNA levels decreased in a dose-dependent manner in the
      presence of increasing concentrations (30-100 ng/ml) of activin with FSH. These
      observations indicate that an increase in cAMP causes down-regulation of LH/hCG
      receptor mRNA and contributes to the effect of FSH and hCG, whereas basal cAMP
      activity is required for LH/hCG receptor mRNA expression.

PMID- 9037197
TI  - Expression of highly active recombinant NS3 protease domain of hepatitis C virus
      in E. coli.
AB  - The serine protease domain of HCV comprising amino acids 1027-1218 (deltaNS3) was
      expressed in E. coli with a His tag at its N-terminal end. The protease was
      purified to apparent homogeneity by a single step affinity chromatography
      resulting in high yields (approximately 3 mg/l of cultured cells). The deltaNS3
      efficiently cleaves a 17-mer peptide corresponding to the NS5A-NS5B junction with
      kcat/Km = 160 x 10(-3) min(-1) microM(-1) in the presence of NS4A peptide. Our
      deltaNS3 represents the minimal domain possessing highly active protease of NS3
      constructed so far. The deltaNS3 protein also efficiently processed a longer
      substrate corresponding to NS5A/5B junction (2203-2506 amino acids) that was
      synthesized by in vitro transcription and translation system.

PMID- 9037196
TI  - Role of the Cys90, Cys95 and Cys173 residues in the structure and function of the
      human platelet-activating factor receptor.
AB  - Platelet-activating factor (PAF) is a potent phospholipid mediator which binds to
      a specific, high affinity receptor of the G protein-coupled receptor family. In
      the present report, we show that ligand binding to the PAF receptor is sensitive
      to the reducing agent dithiothreitol (DTT), suggesting the involvement of
      disulfide linkages in the proper PAF receptor conformation. Substitutions of
      Cys90, Cys95 and Cys173 to Ala or Ser demonstrated that these cysteine residues
      are critical for normal cell surface expression of the PAF receptor protein and
      ligand binding to the receptor. The Cys90 and Cys173 mutant receptors did not
      display any specific ligand binding, were not expressed on the cell surface but
      were found in the intracellular compartment. The Cys95 mutants showed specific
      binding and were able to stimulate low levels of inositol phosphate (IP)
      production. These mutants were expressed at low density on the cell surface and
      showed high expression intracellularly. Our results suggest that the structure
      and function of the PAF receptor require the conserved Cys90 and Cys173 to form a
      disulfide bond. Moreover, Cys95 also appears to be necessary, possibly by
      establishing a disulfide linkage with an as yet unidentified Cys residue. All
      three residues appear essential for the proper folding and surface expression of
      the PAF receptor protein.

PMID- 9037198
TI  - Transforming growth factor-beta negatively modulates T-cell responses in sepsis.
AB  - Sepsis is associated with depressed T-cell functions and increased circulating
      levels of immunosuppressive agents. TGF-beta is a potential anti-inflammatory
      cytokine that can modify T-cell growth and differentiation. The up-regulation of
      TGF-beta and the mechanism of its action on the T-cells during septic injury have
      not been resolved. We hypothesized that in sepsis TGF-beta produced by
      macrophages acts on T-cells in a paracrine manner to suppress interleukin (IL)-2
      production and proliferation. In this study, we examined the circulating TGF-beta
      levels in a rat model of Gram-negative bacterial sepsis, and compared the
      abilities of adherent and non-adherent splenocytes to produce TGF-beta.
      Additionally, we investigated the causal relationships of hrTGF-beta to
      concanavalin A (ConA)-induced T-cell responses and the intracellular mechanism of
      the generation of these responses in normal splenic rat T-cells. Sepsis was
      induced in rats by intraabdominally implanting fecal pellets containing
      Escherichia coli (150 CFU) and Bacteroides fragilis (10000 CFU). Adherent and non
      adherent splenocytes were isolated by differential adherence using Ficoll
      gradient centrifugation. T-cells were purified by use of Nylon wool columns. We
      observed a 3-6-fold increase in the circulating levels of TGF-beta in sepsis.
      Western blots and ELISA determinations revealed a 2.5-3-fold increase in cell
      associated TGF-beta protein levels in adherent splenic cells. Northern analyses
      also showed a marked increase in TGF-beta mRNA expression in adherent cells
      during sepsis. On the other hand, a significant change was not observed in the
      TGF-beta protein and mRNA expression in non-adherent splenocytes. Pretreatment of
      control rat T-cells with hrTGF-beta decreased both ConA-induced proliferation (by
      35-40%) and IL-2 mRNA expression (by > 50%). Further, whereas incubation of
      control rat T-cells with either ConA or TGF-beta for 24 h resulted in a 10-15
      fold increase in cAMP generation, the addition of hrTGF-beta along with ConA
      resulted in a 50-60-fold increase in cAMP. These results suggest that in sepsis,
      TGF-beta produced by splenic macrophages can act in a paracrine manner on T-cells
      to depress their IL-2 mRNA expression, IL-2 production and proliferation after up
      regulation of cAMP which can interfere with T-cell signaling for proliferation.

PMID- 9037199
TI  - Isolation of a mouse MT2-MMP gene from a lung cDNA library and identification of
      its product.
AB  - We have isolated a new MT-MMP related gene of 3.3 kb from a mouse lung cDNA
      library using a human MT1-MMP cDNA as a probe. The deduced protein sequence shows
      87% homology to human MT2-MMP and 52, 50 and 29% to MT1-MMP, MT3-MMP and MT4-MMP,
      respectively. Thus the gene is thought to be a mouse homologue of human MT2-MMP.
      A monoclonal antibody raised against a synthetic peptide recognized mouse MT2-MMP
      as a 70 kDa protein. Like MT1- and MT3-MMPs, mouse MT2-MMP caused activation of
      progelatinase A upon co-transfection into COS-1 cells.

PMID- 9037200
TI  - Regulation of hyaluronate metabolism by progesterone in cultured fibroblasts from
      the human uterine cervix.
AB  - The effects of progesterone, dehydroepiandrosterone sulfate and 17beta-estradiol
      on the synthesis and degradation of hyaluronate were investigated using human
      uterine cervix fibroblasts. The cells were incubated with [3H]glucosamine in the
      presence of the hormones and then [3H]hyaluronate was isolated from the medium.
      The changes in the radioactivity of [3H]hyaluronate showed that progesterone
      suppressed hyaluronate synthesis by 22% of the control levels, while
      dehydroepiandrosterone sulfate and 17beta-estradiol enhanced it by 22% and 12% of
      the control levels, respectively. Furthermore, progesterone induced degradation
      of high-molecular-weight [14C]hyaluronate into low-molecular-weight hyaluronate
      (Mr approximately 40000). These results suggest that in cultured fibroblasts from
      the human uterine cervix progesterone converts hyaluronate metabolism from the
      synthesis phase to the degradation phase.

PMID- 9037201
TI  - A novel, calcium-inhibitable casein kinase in Paramecium cells.
AB  - This is the first identification of a Ca2+-inhibitable casein kinase (CPK) which
      we have isolated from the 100000 x g supernatant of Paramecium cell homogenates.
      The 1000-fold enriched CPK activity depends on millimolar Mg2+ and is inhibited
      by low concentrations of heparin or by > or = 100 microM Ca2+. Enzyme activity is
      stimulated by polylysine or polyarginine with either casein or with specific
      casein kinase-2 (CK-2) peptide substrates (RRRDDDSDDD and RREEETEEE). The enzymic
      properties are similar with GTP instead of ATP. CPK does not undergo
      autophosphorylation. In gel kinase assays, enzyme activity is associated with a
      36 kDa band. Calmodulin as another characteristic substrate for mammalian CK-2
      has not been phosphorylated by this protein kinase. Besides casein, CPK
      phosphorylates in vitro the catalytic subunit of bovine brain calcineurin (CaN),
      a typical substrate of type 1 mammalian casein kinase (CK-1) in vitro. Again this
      phosphorylation is significantly reduced by Ca2+. Thus, CPK combines aspects of
      different casein kinases, but it is clearly different from any type known by its
      Ca2+ inhibition. Since CPK also phosphorylates the exocytosis-sensitive
      phosphoprotein, PP63, in Paramecium, which is known to be dephosphorylated by
      CaN, an antagonistic Ca2+-effect during phosphorylation/dephosphorylation cycles
      may be relevant for exocytosis regulation.

PMID- 9037202
TI  - Depolymerization of malarial hemozoin: a novel reaction initiated by blood
      schizontocidal antimalarials.
AB  - Malaria parasite digests hemoglobin and utilizes the globin part for its
      nutritional requirements. Heme released as a byproduct of hemoglobin degradation
      is detoxified by polymerization into a crystalline, insoluble pigment, known as
      hemozoin. We have identified a novel reaction of depolymerization of hemozoin to
      heme. This reaction is initiated by the interaction of blood schizonticidal
      antimalarial drugs with the malarial hemozoin. The reaction has been confirmed,
      with the purified hemozoin as well as the lysate of the malaria parasite. Pigment
      breakdown was studied by infrared spectroscopy, thin-layer chromatography and
      spectrophotometric analysis. It was complete within 2 h of drug exposure, which
      explains the selective sensitivity of late stages (trophozoites and schizonts) of
      malarial parasites loaded with the hemozoin pigment to the toxic action of these
      drugs. It is suggested that the failure of the parasite heme detoxification
      system due to this reaction results in the accumulation of toxic heme, which
      alone, or complexed with the antimalarial leads to the death of malaria parasite.

PMID- 9037203
TI  - Defining the minimal structural requirements for partial agonism at the type I
      myo-inositol 1,4,5-trisphosphate receptor.
AB  - The novel synthetic analogues D-3-fluoro-myo-inositol 1,5-bisphosphate-4
      phosphorothioate, [3F-Ins(1,5)P2-4PS], D-3-fluoro-myo-inositol 1,4-bisphosphate-5
      phosphorothioate [3F-Ins(1,4)P2-5PS], and D-3-fluoro-myo-inositol 1-phosphate-4,5
      bisphosphorothioate [3F-Ins(1)P-(4,5)PS2] were utilised to define the structure
      activity relationships which could produce partial agonism at the Ca2+ mobilising
      myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor. Based on prior
      structure-activity data we hypothesised that the minimal structural requirements
      for lns(1,4,5)P3 receptor partial agonism, were phosphorothioate substitution of
      the crucial vicinal 4,5-bisphosphate pair accompanied by another structural
      perturbation, such fluorination of 3-position of the myo-inositol ring. All the
      analogues fully displaced [3H]Ins(1,4,5)P3 from a single Ins(1,4,5)P3 binding
      site in pig cerebellar membranes [3F-Ins(1,5)P2-4PS (1C50 = 26 nM), 3F-Ins(1,4)P2
      5PS (IC50 = 80 nM) and 3F-Ins(1)P-(4,5)PS2 (IC50 = 109 nM) cf. Ins(1,4,5)P3 (IC50
      = 11 nM)]. In contrast, 3F-Ins(1,5)P2-4PS (IC50 = 424 nM) and 3F-Ins(1,4)P2-5PS
      (IC50 = 3579 nM) were weak full agonists at the Ca2+ mobilising Ins(1,4,5)P3
      receptor of permeabilised SH-SY5Y neuroblastoma cells, being respectively 4- and
      36-fold less potent than Ins(1,4,5)P3 (EC50 = 99 nM). While 3F-Ins(1)P-(4,5)PS2
      (EC50 = 11345 nM) was a partial agonist releasing only 64.3 +/- 1.9% of the
      Ins(1,4,5)P3-sensitive intracellular Ca2+ pools. 3F-Ins(1)P-(4,5)PS2 was unique
      among the Ins(1,4,5)P3 receptor partial agonists so far identified in having a
      relatively high affinity for the Ins(1,4,5)P3 binding site, accompanied by a
      significant loss of intrinsic activity for Ca2+ mobilisation. This improved
      affinity was probably due to the retention of the 1-position phosphate, which
      enhances interaction with the Ins-(1,4,5)P3 receptor. 3F-Ins(1)P-(4,5)PS2 may be
      an important lead compound for the development of efficient Ins(1,4,5)P3 receptor
      antagonists.

PMID- 9037204
TI  - Suppression of insulin-stimulated phosphatidylinositol 3-kinase activity by the
      beta3-adrenoceptor agonist CL316243 in rat adipocytes.
AB  - Insulin increased 2-deoxyglucose (2-DG) uptake via the translocation of glucose
      transporter (GLUT) 4 to the plasma membrane fraction in rat adipocytes. The
      stimulatory actions of insulin were accompanied by both an increase in the
      immunoreactive p85 subunit of phosphatidylinositol (PI) 3-kinase in the plasma
      membrane fractions and PI 3-kinase activation by tyrosine phosphorylation of the
      p85 subunit. The beta3-adrenoceptor agonist CL316243 (CL) suppressed all the
      insulin actions in adenosine deaminase (ADA)-treated cells, but was without
      effect in non-ADA-treated cells. The inhibitory effects of CL on GLUT 4
      translocation and PI 3-kinase activation were abolished by the addition of N6
      phenylisopropyl adenosine. Cholera toxin treatment, which markedly increased
      intracellular cAMP levels, suppressed increases in the levels of GLUT 4 and PI 3
      kinase in the plasma membrane fractions in response to insulin. In addition,
      dibutyryl (Bt2) cAMP also impaired the activation of PI 3-kinase by insulin.
      These results indicated that CL suppressed insulin-stimulated glucose transport
      under conditions where cAMP levels were markedly increased (approximately 12
      fold). The inhibitory actions of PI 3-kinase activation by insulin were exerted
      even when cAMP, 8-bromo-cAMP, or Bt2 cAMP was added to immunoprecipitates of the
      p85 subunit of PI 3-kinase, after treating the cells with insulin. These results
      suggest that CL suppressed insulin-stimulated PI 3-kinase activity via a cAMP
      dependent mechanism, at least in part, direct cAMP action in ADA-treated
      adipocytes, by which PI 3-kinase activation was inhibited, resulting in the
      decrease in GLUT 4 translocation and subsequent 2-DG uptake in response to
      insulin.

PMID- 9037205
TI  - Regulation of maltose utilization in Saccharomyces cerevisiae by genes of the
      RAS/protein kinase A pathway.
AB  - In Saccharomyces cerevisiae maltose utilization requires a functional MAL locus,
      each composed of three genes: MALR (gene 3) encoding a regulatory protein, MALT
      (gene 1) encoding maltose permease and MALS (gene 2) encoding maltase. We show
      that constitutive activation of the RAS/protein kinase A pathway severely reduces
      growth of MAL1 strains on maltose. This may be a consequence of reduction in MALT
      mRNA, reduced Vmax and increased catabolite inactivation of the MALT-encoded
      maltose transporter in the MAL1 strain. Mutations in the GGS1/TPS1 gene, which
      restricts glucose influx and possibly affects signalling, relieve carbon
      catabolite repression on both maltase and maltose permease and reduce maltose
      permease inactivation.

PMID- 9037206
TI  - The Caenorhabditis elegans death protein Ced-4 contains a motif with similarity
      to the mammalian 'death effector domain'.
AB  - In the nematode Caenorhabditis elegans apoptosis is tightly regulated by a
      hierarchical set of genes. Two of these, ced-3 and ced-9, possess mammalian
      homologues encoding executional ICE proteases and inhibitory Bcl-2-related
      proteins, respectively. The function of a third key player, ced-4, is however
      completely unknown and no mammalian counterparts have been identified. Here we
      report that Ced-4 protein contains a structural region with similarity to the
      mammalian death effector domain which has previously been demonstrated to act as
      an important protein interaction motif in the signaling pathway of the mammalian
      surface receptor Fas (APO-1, CD95). Based on this finding and previously
      described genetic experiments, we propose that Ced-4, similar to the mammalian
      proteins FADD and FLICE, may possess a function as an adaptor protein in
      invertebrate apoptotic pathways.

PMID- 9037207
TI  - Calcium mediates the activation of the inhibitory current induced by odorants in
      toad olfactory receptor neurons.
AB  - In toad olfactory neurons, a putrid odorant mixture inducing inhibitory responses
      increases Ca2+-activated K+ conductance, developing a hyperpolarizing receptor
      potential. Removal of extracellular Ca2+ or exposure to nifedipine reversibly
      reduced the inhibitory response, suggesting that odorants induce a Ca2+ influx.
      We show evidence for an odorant-induced Ca2+ current. Using confocal microscopy,
      it is shown that odorants induce a nifedipine-sensitive elevation of Ca2+ in the
      apical end of the cell. These results suggest an inhibitory mechanism in which an
      apical Ca2+ influx causes an increase in internal Ca2+, opening Ca2+-activated
      K2+ channels that lead to membrane hyperpolarization.

PMID- 9037208
TI  - Urokinase-mediated transactivation of the plasminogen activator inhibitor type 2
      (PAI-2) gene promoter in HT-1080 cells utilises AP-1 binding sites and
      potentiates phorbol ester-mediated induction of endogenous PAI-2 mRNA.
AB  - Urokinase-type plasminogen activator (u-PA) bound to its receptor, u-PAR,
      initiates signal transduction pathways able to induce expression of the activator
      protein-1 (AP-1) family member c-fos [1]. Since transcription factors bound to AP
      1 recognition sequences within the PAI-2 gene promoter play a role in basal and
      phorbol ester-mediated induction of PAI-2 gene expression, we hypothesised that u
      PA/u-PAR-mediated modulation of AP-1 activity would in turn influence
      constitutive and inducible PAI-2 gene expression. Treatment of HT-1080 or U-937
      cells with high molecular weight u-PA (HMW u-PA) resulted in induction of nuclear
      proteins binding to a functional AP-1 element in the proximal PAI-2 promoter.
      This increase in AP-1 activity correlated with a transactivation of the PAI-2
      gene promoter in transiently transfected HT-1080 cells. We also demonstrate the u
      PA treatment potentiated phorbol ester (PMA)-mediated induction of PAI-2 mRNA,
      indicating that u-PA binding produces a bone fide response in vivo.

PMID- 9037209
TI  - Differential splicing of the growth hormone-releasing hormone gene in rat
      placenta generates a novel pre-proGHRH mRNA that encodes a different C-terminal
      flanking peptide.
AB  - We have isolated and characterized a novel rat placental pre-proGHRH mRNA (pre
      proGHRH-2 mRNA). This mRNA is generated by an alternative splicing process which
      results in the presence of an additional exon of 156 bp (designated exon 4.5)
      located between exons 4 and 5 of the previously reported hypothalamic and
      placental pre-proGHRH mRNA (pre-proGHRH-1 mRNA). Since the sequences encoding
      mature GHRH are included within exons 3 and 4, the processing of pre-proGHRH-2
      would not affect the synthesis of mature GHRH but would generate a C-terminal
      peptide (designated GCTP-2) different from that previously reported in the
      hypothalamus and placenta (GCTP-1). The putative GCTP-2 has 64 amino acids, and
      the first 18 N-terminal residues are identical to those present in GCTP-1 (30
      amino acids long). Pre-proGHRH-2 mRNA has not been detected in the hypothalamus.

PMID- 9037210
TI  - Monoclonal antibodies that distinguish between free and complexed heterotrimeric
      G protein beta subunits.
AB  - Heterotrimeric G proteins were purified from bovine brain by immunoaffinity
      chromatography on immobilized anti G protein monoclonal antibody 3C2. Release of
      betagamma subunits was effectuated by exposure of immobilized trimeric G proteins
      to MgAlF4. The resultant betagamma subunits were pure and biologically active.
      Following immunization of mice with purified betagamma subunits we obtained
      monoclonal anti beta antibodies showing broad species cross-reactivity.
      Characterization of the epitope recognized by one such monoclonal antibody, ARC9,
      indicated involvement of the extreme COOH-terminus, as assessed by its reactivity
      on beta subunits lacking the COOH-terminal 15 residues, obtained by in vitro
      translation. Although we used native betagamma subunits as immunogen, all
      monoclonal antibodies obtained failed to recognize assembled betagamma subunits,
      and were specific for free beta subunits. This property is useful in
      characterizing the assembly of G proteins from their subunits in living cells.

PMID- 9037211
TI  - Modifications of proteoglycans secreted into the growth medium by young and
      senescent human skin fibroblasts.
AB  - The properties of proteoglycans (PGs) secreted into the growth medium by normal
      young and senescent human skin fibroblasts (HFs) were investigated. In both
      cases, the incorporation per cell of radioactive precursors into total PGs was
      similar. The polysaccharide chains of PGs from young and senescent HFs were
      mainly represented by galactosaminoglycuronans and showed a similar range of size
      distribution. However, galactosaminoglycuronans of PGs secreted by senescent HFs
      had a lower content of unsulphated disaccharides and a lower proportion of D
      glucuronosyl residues. Moreover, senescent HFs released into the growth medium
      higher relative amounts of small PGs with chondroitin sulphate, dermatan sulphate
      chains, such as decorin.

PMID- 9037212
TI  - Commentary on: 'Effect of purified soluble urokinase receptor on the plasminogen
      prourokinase activation system' by N. Behrendt and K. Dano, FEBS Letters, 393
      (1996) 31-36.

PMID- 9037213
TI  - Reply to comment on 'Effect of purified, soluble urokinase receptor on the
      plasminogen-prourokinase activation system' (A. A-R. Higazi)

PMID- 9037214
TI  - Contraction of the abdominal muscles associated with movement of the lower limb.
AB  - BACKGROUND AND PURPOSE: Activity of the trunk muscles is essential for
      maintaining stability of the lumbar spine because of the unstable structure of
      that portion of the spine. A model involving evaluation of the response of the
      lumbar multifidus and abdominal muscles to leg movement was developed to evaluate
      this function. SUBJECTS: To examine this function in healthy persons, 9 male and
      6 female subjects (mean age = 20.6 years, SD = 2.3) with no history of low back
      pain were studied. METHODS: Fine-wire and surface electromyography electrodes
      were used to record the activity of selected trunk muscles and the prime movers
      for hip flexion, abduction, and extension during hip movements in each of those
      directions. RESULTS: Trunk muscle activity occurring prior to activity of the
      prime mover of the limb was associated with hip movement in each direction. The
      transversus abdominis (TrA) muscle was invariably the first muscle that was
      active. Although reaction time for the TrA and oblique abdominal muscles was
      consistent across movement directions, reaction time for the rectus abdominis and
      multifidus muscles varied with the direction of limb movement. CONCLUSION AND
      DISCUSSION: Results suggest that the central nervous system deals with
      stabilization of the spine by contraction of the abdominal and multifidus muscles
      in anticipation of reactive forces produced by limb movement. The TrA and oblique
      abdominal muscles appear to contribute to a function not related to the direction
      of these forces.

PMID- 9037215
TI  - Physical therapy treatment choices for musculoskeletal impairments.
AB  - BACKGROUND AND PURPOSE: The primary goal of this investigation was to describe
      outpatient physical therapy treatments provided to patients with lumbar,
      cervical, or knee impairments. SUBJECTS: Patients in this analysis received
      outpatient physical therapy for a primary orthopedic complaint during July 1993
      through June 1994 from one of 68 practices participating in the Focus on
      Therapeutic Outcomes database. Data were available on 2,598 completed physical
      therapy episodes of care provided by 141 therapists. METHODS: At each patient's
      discharge, the primary physical therapist gave information on the treatments
      provided to each patient during the initial, middle, and final thirds of the
      episode of therapy as well as information on primary source of reimbursement.
      Patients provided information on the date of onset of their symptoms or surgery.
      RESULTS: These outpatient physical therapy episodes of care were characterized by
      a diverse array of modalities, exercises, and manual therapy treatments.
      Treatment choices varied by type of impairment and across thirds of the episode.
      Fee-for-service versus managed care payment arrangements were associated with
      increased use of devices, therapeutic massage, strengthening, and endurance
      exercises. CONCLUSION AND DISCUSSION: The study's findings revealed that although
      physical agents were frequently used in physical therapy episodes of care, they
      were applied along with exercise and manual therapy interventions. Future
      research should relate specific treatments to variation in patient outcomes
      following physical therapy.

PMID- 9037216
TI  - Covert bias in evaluation of physical therapist students' clinical performance.
AB  - BACKGROUND AND PURPOSE: Physical therapist education programs rely on physical
      therapy practitioners to evaluate the performance of students during clinical
      affiliations. The purpose of this study was to determine whether covert bias
      exists in the evaluative judgments of physical therapy practitioners. SUBJECTS: A
      convenience sample of 83 physical therapists attending the fall conference of the
      Florida Physical Therapy Association was selected. The subjects, 31 men and 52
      women (73 white, 3 black, and 7 Hispanic), had a mean age of 41.5 years (SD =
      8.2, range = 26-73). METHODS: Four female physical therapist students (1 white, 1
      Hispanic, 1 Asian, and 1 black) were videotaped reciting identical scripts about
      a patient's status. Each subject was randomly assigned to one of four groups and
      read a case study about the patient, viewed one videotape, and rated the
      student's presentation on a form developed by the researchers. RESULTS: The
      white, Hispanic, and Asian students received higher ratings than the black
      student on two factors: clarity of presentation and overall rating. The white and
      Hispanic students received a higher rating than the black student on maintaining
      interest. The white and the Asian students received a higher rating than the
      black student on communication of appropriate information. The white student
      received a higher rating than the black student on organization of information.
      CONCLUSION AND DISCUSSION: The black student consistently received low ratings,
      indicating that racial or ethnic bias may influence the opinions of physical
      therapy practitioners. These results justify further exploration of the effect of
      race and ethnicity on student evaluation in the clinic.

PMID- 9037217
TI  - Infrared dermal thermometry for the high-risk diabetic foot.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare skin
      temperatures in patients with asymptomatic peripheral sensory neuropathy,
      patients with neuropathic ulcers, and patients with Charcot's arthropathy using
      the contralateral limb as a control. SUBJECTS: On a retrospective basis, patients
      with diabetes (N = 143) were divided into three groups: patients with
      asymptomatic sensory neuropathy (n = 78), patients with neuropathic foot ulcers
      (n = 44), and patients with neuropathic fractures (Charcot's arthropathy) (n =
      21). METHODS: We evaluated the subjects' skin temperatures with a portable hand
      held infrared skin temperature probe at the time pathology was initially
      identified and at subsequent clinical visits for an average of 22.1 months (SD =
      6.4). Skin temperatures of the contralateral foot were measured as a control.
      RESULTS: There were differences in skin temperature between the affected foot and
      the contralateral (i.e., nonaffected) foot among the patients with Characot's
      arthropathy (8.3 degrees F) and the patients with neuropathic ulcers (5.6 degrees
      F), with no difference identified among the patients with asymptomatic sensory
      neuropathy. Five patients with neuropathic ulcers experienced reulceration a mean
      of 12.2 months (SD = 6.4) after initial healing, with a corresponding increase in
      skin temperature. (89.6 degrees +/- 1.2 degrees F versus 82.5 degrees +/- 2.9
      degrees F) at the clinic visit immediately preceding reinjury. CONCLUSION AND
      DISCUSSION: The data suggest that monitoring of the corresponding contralateral
      foot site may provide clinical information before other clinical signs of injury
      can be identified.

PMID- 9037218
TI  - Regional and fiber-type percentages and sizes in the hamster diaphragm after swim
      training.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of
      a swimming endurance training program on changes in percentages and sizes of
      fiber types in different regions of the hamster diaphragm. METHODS: Adult male
      golden Syrian hamsters were randomly assigned to a control group (n = 9) or a
      swimming group (n = 10). Hamsters in the swimming group swam for 80 minutes per
      session, 5 days per week, for 13 weeks. Fiber-type percentages and sizes were
      determined for the costal region and for the abdominal and thoracic surfaces of
      the crural region of the diaphragm from cross sections processed for myofibrillar
      adenosine triphosphatase. RESULTS: Muscle fibers in the thoracic surface of the
      crural region were smaller in the swimming group than in the control group. Fiber
      type percentages in the diaphragm, however, were not different between groups.
      CONCLUSION AND DISCUSSION: Swim training may have improved the endurance of the
      thoracic/crural region by decreasing cross-sectional area and thus decreasing the
      distance for oxygen to diffuse to the internal regions of the muscle fibers.

PMID- 9037219
TI  - Oxygen transport deficits in systemic disease and implications for physical
      therapy.
AB  - The purposes of this article are to discuss the effects of some common systemic
      diseases on cardiopulmonary function and oxygen transport and to describe the
      implications for physical therapists. Pathology of every major organ system can
      manifest secondary effects on cardiopulmonary function and oxygen transport. Such
      effects are of considerable clinical significance given that they can be life
      threatening and that physical therapy usually stresses the oxygen transport
      system. This article reviews the cardiopulmonary effects of hematologic,
      neuromuscular, musculoskeletal, gastrointestinal, hepatic, renal, collagen
      vascular and connective tissue, endocrine, and immunologic conditions. The
      cardiopulmonary manifestations of some common nutritional disorders (eg, obesity,
      anorexia nervosa) are also discussed. Physical therapists need to be able to
      anticipate, detect, and manage the cardiopulmonary manifestations of systemic
      disease given medical advances and the increasing number of patients with
      multisystem problems, the aging of the population, the expanding scope of
      physical therapy practice, and the increased professional and ethical
      responsibility associated with direct patient access.

PMID- 9037220
TI  - Minimum continuing education requirements.

PMID- 9037221
TI  - Risk factors associated with rapid growth of small abdominal aortic aneurysms.
AB  - BACKGROUND: Approximately 50% of patients who have a ruptured abdominal aortic
      aneurysm will die. To identify those patients who may be at high risk for
      rupture, we determined the risk factors for the rapid expansion of the aorta.
      METHODS: The growth of 514 aneurysmal aortas was followed in this study. The size
      of each was measured by ultrasonography at 6- to 12-month intervals until a
      critical size was reached or a rapid expansion of the aorta occurred. Possible
      risk factors for rapid expansion were determined from both initial evaluation and
      clinical laboratory results. RESULTS: The initial size varied from 2.5 cm to 6.0
      cm. The expansion rate of the aorta was 0.5 cm/yr or less in 401 patients (78%),
      between 0.5 and 1.0 cm/year in 50 patients (10%), and 1.0 cm/year or more (rapid
      expansion) in 63 patients (12%). Elective repair of aneurysms was done before
      rupture. Multivariate analysis indicated that the risk factors associated (p <
      0.03) with rapid expansion were advanced age, severe cardiac disease, previous
      stroke, and history of cigarette smoking. The incidence for rapid expansion
      increased (p < 0.01) in older patients with aneurysms larger than 3 cm and in
      younger patients with aneurysms larger than 4 cm. CONCLUSIONS: Risk factors
      associated with rapid expansion of the aorta have been determined and may help
      identify the patient at high risk for rupture. Ultrasonographic surveillance
      should be performed more frequently in these patients to help prevent rupture.

PMID- 9037222
TI  - A double-blind study of perioperative steroid requirements in secondary adrenal
      insufficiency.
AB  - BACKGROUND: Patients treated long-term with supraphysiologic doses of
      glucocorticoids experience secondary adrenal insufficiency and are routinely
      given large doses of steroids in the perioperative period to prevent hypotension.
      Because the dose of steroids required to prevent hypotension is not known, we
      conducted a randomized, double-blind study to determine whether patients treated
      long-term with glucocorticoids actually require increased steroids in the
      perioperative period. METHODS: Patients who had been taking at least 7.5 mg
      prednisone daily for several months and had secondary adrenal insufficiency as
      defined by adrenocorticotropic hormone testing formed the study population.
      Patients were randomized to two groups. One group received perioperative
      injections of saline solution alone; the other received perioperative saline
      solution and cortisol. All patients received their usual daily prednisone dose
      throughout the study. RESULTS: Six patients were in the steroid-treated group and
      12 were in the saline-treated group. Most subjects underwent major operations
      such as joint replacements, abdominal operations, and miscellaneous other
      procedures. Two patients had hypotension, one in each group. Hypotension resolved
      with volume replacement in both patients. The average pulse rates and blood
      pressures were similar in both groups during the perioperative period.
      CONCLUSIONS: Patients with secondary adrenal insufficiency do not experience
      hypotension or tachycardia caused by inadequate glucocorticoid levels when given
      only their daily dose of steroids for surgical procedures.

PMID- 9037223
TI  - Role of right hepatic lobectomy in the treatment of isolated right-sided
      hepatolithiasis.
AB  - BACKGROUND: The role of right hepatic lobectomy is evaluated in the treatment of
      selected patients with isolated right-sided hepatolithiasis. METHODS: During the
      past 7 years right hepatic lobectomy was performed in five patients who had
      isolated right-sided hepatolithiasis. The rationale and indications of this
      procedure are discussed. The efficacy of preoperative evaluations, the operative
      findings, and the operative results are analyzed. RESULTS: All the patients were
      female with a mean age of 49.2 years (range, 33 to 63 years). The main symptoms
      were upper abdominal pain (n = 5), fever (n = 4), and jaundice (n = 2). The mean
      operative time was 166.4 minutes, and the mean blood loss was 880 ml. The
      complete stone clearance rate was 100%. No operative deaths occurred. Right
      subphrenic abscess with reactive pleural effusion developed in two patients. Echo
      guided percutaneous drainage was applied to one patient, and no surgical
      intervention was needed. The mean follow-up period from the treatment was 13.4
      months (range, 6 to 18 months). During the follow-up period no stone recurrence
      was found. CONCLUSIONS: Right hepatic lobectomy is indicated in patients who have
      localized right-sided hepatolithiasis with irreversible biliary stricture
      involving the right hepatic duct, an atrophied right lobe of the liver, multiple
      cholangitic abscesses, or possible presence of cholangiocarcinoma. Preoperative
      evaluations, including cholangiography, abdominal ultrasonography, and computed
      tomography, are important for the accurate selection of patients and successful
      treatment.

PMID- 9037225
TI  - Progressive necrosis after hepatectomy and the pathophysiology of liver failure
      after massive resection.
AB  - BACKGROUND: Mortality after hepatectomy in rats increases markedly beyond the
      classic 2/3 resection from which complete recovery is the rule. Because an
      extremely small hepatocyte population can theoretically sustain life, we
      hypothesize that lethal liver failure after subtotal resection could be due to
      progressive injury occurring in the remnant liver. The obligatory increase in
      portal blood through the small remnant may be central to the pathogenesis because
      of sinusoidal injury and Kupffer's cell activation. To test this hypothesis an
      experimental study in rats was undertaken to characterize liver cell injury after
      lethal (85%) and nonlethal (70%) hepatectomy. METHODS: One hundred thirty Wistar
      rats were divided into three groups: control group (Sham laparotomy, n = 30),
      70[5] hepatectomy group (n = 50), and 85% hepatectomy group (n = 50). Five rats
      in each group were killed for blood and liver collections from 15 minutes to day
      14 after hepatectomy. Survival, histologic characteristics, serum activities of
      aspartate (AST) and alanine (ALT) aminotransferases and arginase were determined;
      serum level of tumor necrosis factor-alpha (TNF-alpha) and plasma level of
      prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay.
      RESULTS: Whatever the extent of resection, hepatic injury, as demonstrated by
      increased serum levels of arginase, ALT, and AST, was observed. The kinetics of
      arginase release after hepatectomy mimicked quite well those of AST and ALT,
      representing a reliable marker of hepatocyte injury. A significantly higher, more
      prolonged blood release of enzymes was observed after 85% hepatectomy than after
      70% hepatectomy. Because of a very short half-life the rise in arginase several
      hours after hepatectomy seems to indicate ongoing liver damage distinct from the
      surgical injury. Significant elevations of TNF-alpha were detected that were much
      more severe after 85% hepatectomy. PGE2 levels that increased significantly after
      70% resection remained depressed after 8% hepatectomy. Light microscopy
      demonstrated extensive patchy necrosis after 85% hepatectomy. CONCLUSIONS: A
      pattern of progressive necrosis of the remnant liver was identified with
      Kupffer's cell dysfunction. We hypothesize that failure of down-regulation of TNF
      alpha production by PGE2 could contribute to the pathophysiology of liver injury
      in the remnant after massive hepatectomy. These events may be initiated in part
      by the dramatic increase of portal flow through a too small remaining liver, and
      a pathologic mechanism may be amenable to pharmacologic manipulation.

PMID- 9037224
TI  - Efficacy and safety of preoperative percutaneous transhepatic portal embolization
      with absolute ethanol: a clinical study.
AB  - BACKGROUND: Preoperative portal embolization has been performed by using various
      thrombogenic substances to increase the safety and resectability of liver
      surgery. We evaluated the clinical safety and efficacy of using absolute ethanol
      in preoperative portal embolization. METHODS: Our study included 19 patients who
      had undergone right hepatic lobectomy. According to our criteria for right
      lobectomy of the liver, seven patients were not appropriate for the operation
      because of a high risk in each of postoperative liver failure. Those patients
      received preoperative right portal embolization with 11 to 32 ml absolute
      ethanol. The remaining 12 patients satisfied our criteria and received no
      preoperative embolization. RESULTS: Although alanine aminotransferase
      concentrations increased dramatically after the embolization, all serologic
      changes reverted within 3 weeks. The mean volume of the nonembolized lobe
      increased from 320 cm3 to 619 cm3 and 667 cm3 2 and 4 weeks, respectively, after
      embolization. The mean regeneration rate of this lobe was 21.3 cm3 per day for
      the first 2 weeks and 11.4 cm3 per day for the first 4 weeks after embolization.
      All patients underwent right lobectomy of the liver and survived; none of the
      patients had severe complications associated with embolization or surgery. The
      postoperative survival periods were not statistically significant between the
      patients with and without preoperative portal embolization. CONCLUSIONS:
      According to our criteria for liver surgery, the seven patients should not have
      undergone major surgery, but each underwent right lobectomy of the liver and all
      survived, showing that portal embolization with absolute ethanol brings about
      compensatory hepatic hypertrophy for major surgery and that its extreme effect on
      liver regeneration could widen the range of patients appropriate for liver
      surgery.

PMID- 9037226
TI  - Management of aneurysms in Behcet's syndrome: an analysis of 24 patients.
AB  - BACKGROUND: The surgical therapy of Behcet aneurysms is often unsuccessful,
      resulting in graft occlusions, anastomoses, and/or new aneurysms. METHODS: Twenty
      nine aneurysms were documented in 24 Behcet's patients during a period of 19
      years. All patients were male, ranging in age from 20 to 53 years (mean, 35 +/-
      7.3 years). The mean duration of disease was 9 +/- 5 years. There were nine
      abdominal aorta, four iliac, three common femoral, five superficial femoral, four
      popliteal, one subclavian, one carotid, and one posterior tibial artery aneurysm.
      In addition, in one patient an aneurysm developed from the arterialized venous
      conduit that had been inserted for a common femoral artery aneurysm elsewhere.
      Five patients were already under immunosuppressive therapy for ocular problems at
      the time of diagnosis. Fifteen patients received immunosuppressive therapy after
      operation. We performed one abdominal aneurysmorrhaphy, two iliac artery PTFE
      graft interpositions, two aortobiliac bypasses (PTFE), six aortic tube graft
      (three PTFE, three Dacron) interpositions, one avrtofemoral bypass (PTFE), two
      iliofemoral bypasses (PTFE), two superficial femoral artery graft (PTFE)
      interpositions, and three popliteal graft interpositions (one PTFE, two vein
      graft). Also as an initial procedure one carotid, one subclavian, four
      superficial femoral, one popliteal, and one posterior tibial artery were ligated.
      RESULTS: Nineteen patients were followed up for a mean duration of 47.3 +/- 27
      months (range, 1 to 108 months). The patient with a subclavian aneurysm died of
      massive bleeding on postoperative day 15. Four patients were lost to follow-up.
      In the abdominal aortic aneurysm group one patient died of gastrointestinal
      bleeding 4 years after the operation. Another patient from the same group died 5
      years after operation without any vascular disease. In the common femoral artery
      group the patient with an occluded iliofemoral graft died of an exsanguinating
      pulmonary artery aneurysm in the first year after operation. Overall, there were
      five anastomotic aneurysms. In addition, after the initial operation two
      iliofemoral, one aortofemoral, and one popliteal interposition graft were
      occluded without disabling ischemia. CONCLUSIONS: Aneurysms limited to the
      extremities could be ligated without disabling ischemia. Abdominal aortic
      aneurysms could be treated with tube graft insertion, giving satisfactory
      results. Patients could tolerate graft occlusion without major ischemia.

PMID- 9037227
TI  - Time course of regression of left ventricular hypertrophy after successful
      parathyroidectomy.
AB  - BACKGROUND: We have shown that primary hyperparathyroidism may induce myocardial
      hypertrophy that is reversible after successful parathyroidectomy. The present
      study was designed to assess the time course of regression of left ventricular
      hypertrophy without further effects of drug treatment or disease states. METHODS:
      We performed echocardiographic studies in 16 patients with primary
      hyperparathyroidism and normal resting blood pressure, normal systolic left
      ventricular function, no evidence of valvular disease, and without any current
      medication before parathyroidectomy, as well as during intermediate and long-term
      follow-up after successful parathyroidectomy. RESULTS: Eleven patients (69%) had
      end-diastolic wall thickness of the interventicular septum and/or posterior wall
      greater than 11 mm on baseline echocardiogram. After surgical removal of the
      inciting disease and an average of 12.5 and 45.7 months of follow-up with
      normocalcemia and normal parathyroid hormone levels a prolonged regression of
      left ventricular hypertrophy was observed (interventricular septum, -0.68 mm at
      12.5 months and -1.69 mm at 45.7 months; p = 0.02; posterior wall, -0.46 mm at
      12.5 months and -2.24 mm at 45.7 months; p = 0.02). CONCLUSIONS: We conclude that
      the removal of the cause of myocardial hypertrophy by successful
      parathyroidectomy leads to a prolonged reversal of hypertrophy. The progressive
      reduction of left ventricular wall thickness is not completed within 12 months.

PMID- 9037228
TI  - Hemodynamic and metabolic effects of vasopressin blockade in endotoxin shock.
AB  - BACKGROUND: Arginine vasopressin V1 receptor antagonist (AVPRA) was administered
      to investigate the influence of vasopressin blockade on hemodynamics and
      metabolism during endotoxin shock. METHODS: Anesthetized rats were divided into
      four groups: control (0.9% saline solution, n = 5), drug control (AVPRA, n = 5),
      endotoxin (endotoxin, 5 mg/kg, n = 10), and pretreatment (AVPRA and endotoxin, n
      = 10). Hemodynamics and oxygen transport were evaluated for 2 hours. Terminal
      arterial and portal venous concentrations of endotoxin, pyruvate, lactate, and
      ketone bodies were determined. RESULTS: The endotoxin group maintained blood
      pressure levels similar to those of control animals. AVPRA pretreatment decreased
      vascular resistance and resulted in lower blood pressure than endotoxin alone.
      Endotoxin decreased oxygen consumption and the oxygen extraction ratio and
      increased arterial lactate concentration and the lactate/pyruvate ratio.
      Endotoxin also decreased arterial ketone body concentration and markedly
      decreased ketone body availability in the mesenteric circulation. AVPRA
      pretreatment improved oxygen consumption, oxygen extraction ratio, and ketone
      body availability; arterial lactate concentration, lactate/pyruvate ratio, and
      arterial ketone body concentration were not affected. Pretreatment with AVPRA
      also decreased arterial and portal venous concentrations of endotoxin.
      CONCLUSIONS: Vasopressin receptor blockade during endotoxemia resulted in lower
      blood pressure than endotoxin alone. Vasopressin receptor blockade also
      maintained oxygen extraction ratio and ketone body availability in the mesenteric
      circulation. Vasopressin may play a key role in the response to endotoxemia.

PMID- 9037229
TI  - In situ neural isolation of the entire canine upper gut: effects on fasting and
      fed motility patterns.
AB  - BACKGROUND: Multiorgan upper gut transplantation is becoming clinically feasible;
      however, the effects of multivisceral transplantations on gastrointestinal
      motility are unknown. Our aim was to determine the neural and hormonal mechanisms
      controlling motility patterns after complete extrinsic denervation of the upper
      gut as a model of multivisceral upper gut autotransplantation. METHODS: Seven
      dogs successfully underwent in situ neural isolation of the stomach, entire small
      intestine, proximal colon, liver, and pancreas by transecting all connections
      (distal esophagus, midcolon, all nerves, lymphatics) to this multivisceral
      complex except the celiac artery, superior mesenteric artery, and the
      suprahepatic and infrahepatic vena cava; these vessels were meticulously stripped
      of adventitia under optical magnification. Blood flow was not disrupted to
      prevent confounding effects of ischemia-reperfusion injury. After 1- to 2-week
      recovery, myoelectric and manometric recordings of stomach and myoelectric
      recordings of small bowel were obtained from conscious animals. RESULTS: During
      fasting the characteristic cycling migrating motor complex (MMC) was observed in
      the stomach and small intestine. The gastric component of the MMC was absent in
      one of the seven dogs. Regular cycling of the MMC during fasting, however, was
      intermittently disrupted and replaced by a noncyclic pattern of intermittent
      contractions in two of seven dogs 43% of the recording time. A small meal (50 gm
      liver) did not abolish the MMC as occurs in normal dogs; in contrast, a large
      meal (500 gm liver) did abolish the MMC. CONCLUSIONS: Extrinsic innervation to
      the upper gut modulates but is not requisite for interdigestive and postprandial
      motility of the stomach. Because relatively normal global motility patterns are
      preserved, multivisceral upper gut transplantation should be a viable option in
      selected patients.

PMID- 9037230
TI  - Postprandial motor activity and its relationship to transit in the canine ileum.
AB  - BACKGROUND: The purpose of this study was to elucidate the mechanism of reduced
      intestinal transit rate in the ileum as compared with the jejunum. METHODS:
      Twenty-one dogs were each instrumented with 12 strain gauge transducers, 2
      collection cannulas, and an infusion catheter defining a 100 cm study in the
      midjejunum (n = 11) and midileum (n = 10). Postprandial motor activity and
      intestinal transit were measured 1 hour after ingestion of a 650 kcal solid meal.
      Contractile activity was analyzed by means of computer programs that determine
      frequency, amplitude, and propagation behavior of circular smooth muscle
      contractions. RESULTS: Postprandial ileal contractions occurred with greater
      frequency (13.7 +/- 2.5 versus 11.5 +/- 0.4; p = 0.04) and displayed a higher
      incidence of propagation (61% +/- 2% versus 44% +/- 3%; p = 0.0001) than jejunal
      contractions, but traveled at significantly slower rates (1.0 +/- 0.7 cm/sec vs
      3.7 +/- 0.9 cm/sec; p = 0.0001). The net result was significantly slower transit
      in the ileum compared with the jejunum (4.7 +/- 0.7 cm/min versus 13.1 +/- 1.5
      cm/min; p = 0.0006). Within each region, transit correlated with parameters of
      propagating contractions. Stepwise regression of the combined data revealed that
      contraction velocity was the most important variable determining intestinal
      transit rate (r = 0.64; p < 0.001). CONCLUSIONS: Contrary to previous thinking,
      postprandial ileal contractions display a high degree of temporal and spatial
      organization. Slow ileal transit is mainly due to reduced propagation velocity,
      which is intrinsic to the circular smooth muscle.

PMID- 9037231
TI  - Urinary adenosine excretion in patients receiving amphotericin B.
AB  - BACKGROUND: Intravenous amphotericin B (AMB) administration in animals causes
      renal vasoconstriction, ischemia, and oliguria that may result in irreversible
      renal injury; the mechanism of AMB nephrotoxicity may be similar in human beings.
      Adenosine is excreted in urine by the ischemic kidney. We hypothesized that
      adenosine excretion and oliguria would be a marker for patients who later would
      manifest AMB-associated renal insufficiency and that pre-AMB saline
      administration (which ameliorates AMB nephrotoxicity) would negate the change in
      adenosine excretion and urine output. METHODS: Twenty hospitalized patients being
      treated at the direction of their attending physician and who were receiving AMB
      (15 to 75 mg intravenously) had urine collected for 1 hour before and for 2 hours
      during AMB infusion. Eleven patients received normal saline solution (500 ml
      intravenously) before the AMB infusion; the other nine formed the comparator
      group. An aliquot of each urine collection was precipitated with perchloric acid
      to remove protein and cellular elements and centrifuged, and the supernatant was
      assayed for adenosine by using high-pressure liquid chromatography. RESULTS:
      Infusion of AMB was associated with a decrease in mean urine output both in
      patients who received saline solution (245 before versus 149 ml/hr during AMB
      infusion, p = 0.04) and in patients in comparator group (139 versus 89 ml/hr, p =
      0.027). The mean urinary adenosine excretion was unchanged in the saline-loaded
      group (0.1354 before versus 0.1255 mmol/hr during drug infusion, p = 0.25) and
      was decreased in the comparator group (0.2276 versus 0.1127 mmol/hr, p = 0.01).
      Development of renal insufficiency did not correlate with the change in urine
      output or adenosine excretion. CONCLUSIONS: AMB infusion in human beings results
      in decreased urine output and decreased adenosine excretion. The latter effect is
      prevented by a pre-AMB saline load. The changes in urine output and adenosine
      excretion are not predictive of the development of renal insufficiency.

PMID- 9037232
TI  - Discordant xenoislets from a large animal donor undergo accelerated graft failure
      rather than hyperacute rejection: impact of immunosuppression, islet mass, and
      transplant site on early outcome.
AB  - BACKGROUND: It is not known whether discordant, free, nonvascularized xenoislets
      akin to discordant, vascularized, solid xenoorgans-are hyperacutely rejected.
      Quantitative xenoislet requirements and the optimal transplant site also remain
      to be defined. METHODS: We studied these questions with a discordant dog-to
      diabetic Lewis rat xenoislet model, using (1) functional (cure of streptozotocin
      induced diabetes) and (2) histologic (biopsies of intraportal grafts) parameters.
      WF-to-Lewis alloislet recipients served as histologic controls. RESULTS: (1) We
      found that 5000 xenoislet equivalents (IEs) transplanted into the portal veins of
      nonimmunosuppressed rats never functioned. Peritransplant combination therapy
      (rapamycin, cyclosporin A, anti-rat lymphocyte serum) significantly prolonged
      graft survival of 5000 intraportal IEs (median, 3 days) but not of 2500
      intraportal or of 5000 intraperitoneal or renal subcapsular IEs. (2) By means of
      immunofluorescence (at 1 hour after transplantation), we noted immunoglobulin M
      (IgM) and IgG binding to islets in xenografts but not allografts; we noted
      complement and fibrinogen binding in both xenografts and allografts. Insulin
      positive islet cells within intact xenoislets were demonstrated in
      nonimmunosuppressed rats up to 48 hours after transplantation. Cellular xenograft
      infiltration and inflammation, beginning at 6 hours, were observed even in
      immunosuppressed rats. (3) Thus, in spite of IgM and IgG binding, intraportal
      discordant xenoislets were not hyperacutely rejected and destroyed. Nevertheless,
      universal xenoislet nonfunction in nonimmunosuppressed rats was immune mediated.
      A large xenoislet mass (more than 10,000 IEs/kg), the intraportal site, and
      combination therapy were absolute prerequisites for immediate function. But even
      if the prerequisites were all fulfilled, accelerated xenoislet graft failure
      occurred. CONCLUSIONS: This outcome suggests that the specific binding of IgM and
      IgG to xenoislets, in conjunction with the binding of complement and fibrinogen,
      contributed to accelerated graft failure. Thus distinction between discordant and
      concordant species combinations is important for free, nonvascularized xenoislet
      transplants. These findings and the steroid-free combination protocol (rapamycin,
      cyclosporin A, anti-T-cell therapy) warrant further testing in preclinical
      discordant xenoislet studies.

PMID- 9037233
TI  - Does pneumoperitoneum with different gases, body positions, and intraperitoneal
      pressures influence renal and hepatic blood flow?
AB  - BACKGROUND: Because of the well-known negative effects of carbon dioxide
      pneumoperitoneum on the hemodynamic and respiratory system, it was questionable
      how pneumoperitoneum may affect hepatic and renal blood flow. Therefore the
      influences of different gases, different intraperitoneal pressures, and different
      body positions on hepatic and renal blood flow were investigated in a porcine
      model. METHODS: Cardiac and hemodynamic function were monitored by means of
      implanted catheters in the pulmonary artery and the femoral vein and artery.
      Renal and hepatic blood flow were recorded with a transonic volume flow meter
      placed at the renal and hepatic arteries and the portal vein. Eighteen animals
      were randomly assigned to receive one of three insufflation gases (carbon dioxide
      [CO2], argon, or helium. After baseline recording, one of three intraperitoneal
      pressures (8, 12, or 16 mm Hg) and one of three body positions (supine head up,
      or head down) were randomly chosen. After an adaptation time of 15 minutes, all
      data were recorded for 15 minutes. This was repeated until all nine combinations
      had been investigated. The end points of the study were blood flow in the hepatic
      and renal arteries and the portal vein, cardial output, systemic vascular
      resistance, and central venous pressure. RESULTS: Total liver blood flow was
      reduced on relation to intraabdominal pressure, head-up position, and argon
      insufflation. Arterial hepatic blood flow was reduced by the head-up position and
      argon insufflation. Portal venous blood flow decreased with the pig in the head
      up position, with increased intraabdominal pressure, and argon insufflation.
      Renal blood flow was reduced by the head-up position and increased pressure.
      There was no correlation (p < 0.6) between systemic hemodynamic parameters
      (cardiac output, central venous pressure, and systemic vascular resistance) and
      hepatic and renal blood flow. CONCLUSIONS: Head-up position and intraperitoneal
      pressure greater than 12 mm Hg should be avoided during laparoscopic surgery
      because they compromise hepatic and renal blood flow. Argon insufflation impairs
      liver blood flow. However, helium may be advantageous compared with CO2
      insufflation.

PMID- 9037234
TI  - Beneficial effects of growth hormone combined with parenteral nutrition in the
      management of inflammatory bowel disease: an experimental study.
AB  - BACKGROUND: Growth hormone (GH) improves net protein anabolism and stimulates
      wound healing. Although GH is also known to exert the trophic effect on the
      intestinal tract, its role in the healing of intestinal ulceration is not known.
      The aim of this study was to evaluate the effects of exogenous GH coinfused with
      parenteral nutrition (PN) in an experimental model of inflammatory bowel disease
      in rats. METHODS: All rats underwent central venous cannulation and were
      randomized to two groups after induction of small intestinal ulceration with
      indomethacin. Both groups received the same PN formula. In addition, the GH group
      (n = 10) received subcutaneous injections of human GH at a dose of 1.0 IU/kg
      daily for 4 days, whereas the control group (n = 10) received injections of
      normal saline solution. Nitrogen balance, macroscopic inflammation score,
      intestinal myeloperoxidase activity, DNA content, and mucosal permeability were
      determined for each rat. Insulin-like growth factor-I (IGF-I) mRNA was detected
      by reverse transcription and polymerase chain reaction. RESULTS: Administration
      of GH significantly improved the cumulative nitrogen balance, ameliorated the
      gross inflammation score, and decreased intestinal myeloperoxidase activity.
      Similarly, intestinal permeability was significantly decreased in the GH group as
      compared with the control group. GH treatment resulted in increased plasma
      concentration of IGF-I and IGF-I mRNA expressions in both the liver and the small
      intestine compared with those in the control group. CONCLUSIONS: Exogenous GH
      plays an important role in accelerating intestinal healing in an experimental
      model of small bowel ulceration in rats. The mechanisms may include the
      stimulated IGF-I production, which thereafter augments intestinal epithelial cell
      growth.

PMID- 9037235
TI  - A new technique of one-stage total hepatectomy in the rat.
AB  - BACKGROUND: A small animal model of one-stage total hepatectomy is needed for the
      study of the consequences of fulminant liver failure and to investigate the
      extrahepatic metabolism of drugs metabolized by the liver. The models of
      hepatectomy described previously in the rat have the disadvantage of multiple
      stages, technical difficulty, or achievement of only an incomplete removal of the
      liver tissue. METHODS: A Y-shaped graft was prepared from the inferior vena cava
      and the left renal vein of a donor rat. A total hepatectomy was performed in a
      recipient rat. The graft was placed and the portorenal and lower cavocaval
      anastomoses were performed by means of the polyethylene cuff technique. The upper
      cavocaval anastomosis was fashioned with a continuous suture. The procedure was
      performed on 49 rats, and the animals were studied for survival and biochemical
      profiles. RESULTS: The surgical procedure took a mean of 40 +/- 5 minutes and was
      not associated with any operative deaths. The portal clamping time did not exceed
      15 minutes. Spontaneous mean survival of the anhepatic rats was 360 +/- 30
      minutes, and glucose supplemented animals had a mean survival time of 20 +/- 5
      hours. The anhepatic state was associated with significant metabolic and
      biochemical alterations. CONCLUSIONS: This procedure is quick to perform and does
      not require considerable microsurgical expertise. It provides a reproducible
      small animal model of total hepatectomy that is particularly useful for metabolic
      studies.

PMID- 9037236
TI  - Outcome studies in surgical research.
AB  - Providers, payers, buyers, and the public at large will continue to demand
      information regarding the quality of health care service. High quality clinical
      and functional data on the entire population would not only allow a better
      understanding of health outcomes after medical or surgical interventions but
      would also provide information regarding disease burden, the population at risk,
      and indications for treatment. We currently are dealing with two separate pieces
      of the puzzle. On the one hand, randomized clinical trials and observational
      studies continue to provide high quality information regarding small samples of
      the population. On the other hand, the analysis of large administrative data sets
      provides a broad overview of health care services and patient outcomes at the
      population level. To provide meaningful data regarding the quality of health
      care, we must go beyond morbidity and mortality rates and attempt to measure
      patient function at the population level.

PMID- 9037237
TI  - Failure of the portal vein to bifurcate.

PMID- 9037238
TI  - Small bowel obstruction by jejunal enterolith.

PMID- 9037239
TI  - Subcapsular hematoma of the spleen associated with acute pancreatitis.

PMID- 9037240
TI  - Incidental Meckel's diverticulectomy.

PMID- 9037241
TI  - Angiographic salvage of a malpositioned Hickman catheter: a cost-effective tool.

PMID- 9037242
TI  - Changes in right ventricular function during laparoscopy (experimental study)

PMID- 9037243
TI  - Splenic abscess associated with pancreatic cancer: report of a case.

PMID- 9037244
TI  - Plant-derived anticancer agents.
AB  - Natural product drugs play a dominant role in pharmaceutical care. This is
      especially obvious in the case of antitumor drugs, as exemplified by paclitaxel
      (Taxol), vincristine (Oncovin), vinorelbine (Navelbine), teniposide (Vumon), and
      various water-soluble analogs of camptothecin (e.g., Hycamtin). The most
      efficient method of discovering drugs such as these (i.e. novel chemical
      prototypes that may function through unique mechanisms of action) is bioactivity
      guided fractionation, and it is certain that additional natural product drugs,
      some of which should be useful for the treatment of humans, remain to be
      discovered. For the commercial procurement of structurally complex natural
      product drugs, isolation from plant material may be most practical. With the
      advent of combinatorial chemistry and high throughput screening, however, even
      greater progress may now be expected with natural product leads. While systemic
      drug therapy, to an appreciable extent based on natural products, has been the
      mainstay of pharmaceutical care, the logic of disease prevention is overwhelming.
      Bearing in mind the pandemic nature of cancer, a proposal is put forth to create
      a cancer chemoprevention drug formulation for utilization on a widespread basis
      by the general population. Cancer chemopreventive agents, many of which are
      natural products, are capable of preventing or inhibiting the process of
      carcinogenesis. As with other pharmaceutical agents useful for disease
      prevention, a pharmacoeconomic analysis of a cancer chemopreventive formulation
      would need to be considered, and the composition of the formulation should
      improve over time. Nonetheless, implementation should commence immediately.

PMID- 9037245
TI  - Effects of piracetam on membrane fluidity in the aged mouse, rat, and human
      brain.
AB  - In vitro preincubation of brain membranes of aged mice with piracetam (0.1-1.0
      mmol/L) enhanced membrane fluidity, as indicated by decreased anisotropy of the
      membrane-bound fluorescence probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Piracetam
      had similar in vitro effects on brain membranes of aged rats and humans, but it
      did not alter brain membrane fluidity in young mice. Chronic treatment of young
      and aged rats with piracetam (300 mg/kg once daily) significantly increased
      membrane fluidity in some brain regions of the aged animals, but had no
      measurable effect on membrane fluidity in the young rats. The same treatment
      significantly improved active avoidance learning in the aged rats only. It is
      suggested that some of the pharmacological properties of piracetam can be
      explained by its effects on membrane fluidity.

PMID- 9037246
TI  - The antiproliferative effect of 8-chloro-adenosine, an active metabolite of 8
      chloro-cyclic adenosine monophosphate, and disturbances in nucleic acid synthesis
      and cell cycle kinetics.
AB  - 8-Chloro-adenosine, the dephosphorylated metabolite of the antineoplastic agent 8
      chloro-cyclic AMP, has been proposed to act on the regulatory subunits of cyclic
      AMP-dependent protein kinase. 8-Chloro-adenosine has a growth-inhibitory effect,
      the mechanism of which is unclear. We investigated the effects of 8-chloro-cyclic
      AMP and 8-chloro-adenosine on nucleic acid synthesis and cell cycle kinetics in
      two human glioma cell lines. These effects were compared to those of the cyclic
      AMP analogue 8-(4-chlorophenyl)-thio-cyclic AMP (8-CPTcAMP), which is less
      susceptible to dephosphorylation. Whereas 8-CPTcAMP almost completely inhibited
      RNA and DNA synthesis, both 8-chloro-adenosine and 8-chloro-cyclic AMP only
      partly inhibited synthesis of RNA and DNA at growth-inhibitory concentrations, as
      demonstrated by using [5-1H] uridine and [14C]thymidine incorporation. Therefore,
      the growth-inhibitory effect of 8-chloro-cyclic AMP is not (or not completely)
      due to activation of cyclic AMP-dependent protein kinase nor to the inhibition of
      nucleic acid synthesis. Flow cytometric analysis revealed that 8-chloro-cyclic
      AMP and 8-chloro-adenosine probably block cell cycle progression at the G2M
      phase. The effects of 8-chloro-cyclic AMP on nucleic acid synthesis and cell
      cycle progression were largely prevented by adenosine deaminase, which
      inactivates 8-chloro-adenosine. This indicates that the effects of 8-chloro
      cyclic AMP were at least in part due to its metabolite 8-chloro-adenosine.
      Incorporation of 8-chloro-adenosine into RNA and DNA might contribute to the
      disturbance of the cell cycle kinetics and growth-inhibitory effect of 8-chloro
      adenosine.

PMID- 9037247
TI  - Effects of antioxidant enzyme modulations on interleukin-1-induced nuclear factor
      kappa B activation.
AB  - Nuclear factor kappa B (NF-kappa B) is a potent and pleiotropic transcription
      factor that can be activated by a wide variety of inducers, including interleukin
      1 (IL-1). Although the detailed activation mechanism of NF-kappa B is still under
      investigation, it requires both phosphorylation and degradation of its inhibitory
      subunit I kappa B and the presence of an oxidative environment. In this study, we
      systematically evaluated the influence of glutathione peroxidase, glutathione
      reductase and catalase on IL-1-induced NF-kappa B activation by analysing the
      effect of specific inhibitors of these enzymes. For the three antioxidant enzymes
      mentioned, their inhibition correlated with an overactivation of NF-kappa B,
      particularly for glutathione peroxidase. Inversely, we tested the response of
      glutathione peroxidase-transfected cells on NF-kappa B activation, which was
      lower as compared with the parental cells. Furthermore, interleukin-6 production
      also correlated perfectly with the reduced level of NF-kappa B activation is
      these experiments. The results clearly show that NF-kappa B activation is,
      strongly dependent on the antioxidant potential of the cells, especially on the
      activity of reduced glutathione-dependent enzymes such as glutathione peroxidase.
      The results support the hypothesis that the level of the oxidised
      glutathione:reduced glutathione ratio and the activity of intracellular
      antioxidant enzymes play a major role in NF-kappa B tine tuning.

PMID- 9037248
TI  - Physicochemical properties, cytotoxic activity and topoisomerase II inhibition of
      2,3-diaza-anthracenediones.
AB  - The physicochemical, cytotoxic and pharmacological properties of 2,3-diaza
      anthracenedione derivatives were examined to gain insight into the structure
      activity relationships in this class of compounds. Spectrophotometric,
      chiroptical and voltammetric measurements were performed, along with cell
      cytotoxicity, alkaline elution, topoisomerase II-mediated DNA cleavage and
      cellular drug-uptake determination. In comparison with classic anthracenediones
      such as mitoxantrone and ametantrone, the aza derivatives were characterized by
      less negative reduction potentials, lower affinity for DNA and modified geometry
      of intercalation. The biological effects of the new compounds were also
      profoundly affected by bioisosteric N for C replacement. Stimulation of
      topoisomerase II-mediated DNA cleavage was not observed, whereas other mechanisms
      of cell cytotoxicity, possibly involving oxidative DNA damage appeared to be
      operative. The inability to generate protein-associated strand breaks could be
      explained by an unfavorable orientation of the drug in the intercalation complex
      rather than by a reduced binding to DNA. Geometry of drug intercalation may have
      a critical influence on the formation of the ternary complex. In turn, the onset
      of a different DNA-damaging pathway is likely to be related to easy redox cycling
      of the 2,3-diaza-substituted anthracenedione derivatives, which could produce
      radical species to a remarkably greater extent than could the carbocyclic parent
      drugs.

PMID- 9037249
TI  - Variable contribution of cytochromes P450 2D6, 2C9 and 3A4 to the 4-hydroxylation
      of tamoxifen by human liver microsomes.
AB  - 4-Hydroxylation is an important pathway of tamoxifen metabolism because the
      product of this reaction is intrinsically 100 times more potent as an oestrogen
      receptor antagonist than is the parent drug. Although tamoxifen 4-hydroxylation
      is catalysed by human cytochrome P450 (CYP), data conflict on the specific
      isoforms responsible. The aim of this study was to define unequivocally the role
      of individual CYPs in the 4-hydroxylation of tamoxifen by human liver microsomes.
      Microsomes from each of 10 human livers catalysed the reaction [range = 0.6-2.9
      pmol/mg protein/min (1 microM substrate concentration) and 6-25 pmol/mg
      protein/min (18 microM)]. Three of the livers with the lowest tamoxifen 4
      hydroxylation activity were from genetically poor metabolisers with respect to
      CYP2D6. Inhibition of activity by quinidine (1 microM), sulphaphenazole (20
      microM) and ketoconazole (2 microM), selective inhibitors of CYPs 2D6, 2C9 and
      3A4, respectively, was 0-80%, 0-80% and 12-57%. The proportion of activity
      inhibited by quinidine correlated positively with total microsomal tamoxifen 4
      hydroxylation activity (rs = 0.89, P < 0.01), indicating a major involvement of
      CYP2D6 in this reaction. Recombinant human CYPs 2D6, 2C9 and 3A4 but not CYPs
      1A1, 1A2, 2C19 and 2E1 displayed significant 4-hydroxylation activity. Similar
      inhibition and correlation experiments confirmed that tamoxifen N-demethylation
      is catalysed predominantly by CYP3A4. These findings indicate that the 4
      hydroxylation of tamoxifen is catalysed almost exclusively by CYPs 2D6, 2C9 and
      3A4 in human liver microsomes. However, the marked between-subject variation in
      the contribution of these isoforms underlines the need to study metabolic
      reactions in a sufficient number of livers that are characterised with respect to
      a range of cytochrome P450 activities.

PMID- 9037250
TI  - Mechanistic studies on metabolic chiral inversion of 4-(4-methylphenyl)-2
      methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of the new
      anti-rheumatic agent 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE
      298), in rats.
AB  - The chiral inversion properties of 4-(4-methylphenyl)-2-methylthiomethyl-4
      oxobutanoic acid (KE-748), an active metabolite of 2-acetylthiomethyl-4-(4
      methylphenyl)-4-oxobutanoic acid (KE-298), were compared with those of ibuprofen
      in rats. After administration of R(-)-[2 alpha-2H]KE-748, S(+)-KE-748 was present
      in the rat plasma, and the deuterium atoms of the S(+)-enantiomer were almost all
      replaced by hydrogen atoms. After administration of S(+)-[2 alpha-2H]KE-748, the
      deuterium content of S(+)-KE-748 in the plasma remained intact. In the in vitro
      study, using a cell-free system and rat liver homogenates, the chiral inversion
      of ibuprofen was apparent when both CoA and ATP were present; however, KE-748 was
      not inverted. In the study on isolated rat hepatocytes, the unidirectional chiral
      inversion from R(-)-to S(+)-enantiomer was observed for both ibuprofen and KE
      748. When R(-)-ibuprofen was incubated with medium and long chain fatty acids
      (carbon chain length C6 to C16), using isolated hepatocytes, the chiral inversion
      decreased significantly. On the other hand, when R(-)-KE-748 was incubated with
      short and medium chain fatty acids (carbon chain length C3 to C8), chiral
      inversion was inhibited markedly. To induce hepatic microsomal long chain fatty
      acid CoA ligase, rats were treated with clofibric acid (CF rats). In both in
      vitro and in vivo experiments on CF rats, chiral inversion from R(-)-to S(+)
      ibuprofen was enhanced significantly compared with that in controls, whereas the
      enhancement was not observed in the case of R(-)-KE-748. There was no influence
      of benzoic acid, a typical substrate on medium chain fatty acid CoA ligase in the
      mitochondrial matrix, on chiral inversion of R(-)-ibuprofen, using, isolated
      hepatocytes. In contrast, the chiral inversion from R(-)-to S(+)-KE-748 was
      strongly inhibited in the presence of benzoic acid. These results indicate that
      chiral inversion of R(-)-KE-748 may proceed via formation of the CoA-thioester
      intermediate with loss of the 2 alpha-methine proton, in a manner similar to that
      seem with R(-)-ibuprofen. However, the enzymes needed to form CoA-thioester of R(
      )-KE-748 differ from those for R(-)-ibuprofen.

PMID- 9037251
TI  - Mechanism for the stabilization in vivo of the aziridine precursor --(4
      acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride by serum proteins.
AB  - Oral and intraperitoneal administration of 2-(4-acetoxyphenyl)-2-chloro-N-methyl
      ethylammonium chloride (Compound A), an analogue of phenyl aziridine precursors
      that occur in the shrub Salsola tuberculatiformis Botsch, had a contraceptive
      effect on female Wistar rats with a concomitant decrease in total body, uterus,
      and every mass and an increase in abronal mass. Compound A elicited a Type II
      difference spectrum and inhibited the Type I deoxycorticosterone (DOC) induced
      difference spectrum of sheep adrenal cytochrome P450c11 in a manner similar to
      that of S2, a biologically active fraction isolated from S. tuberculatiformis.
      The effects of Compound A on the spectral properties of P450c11 were diminished
      with time in PBS. Electrospray mass spectrometry (ES-MS) indicated that the rate
      of cyclization of Compound A to the corresponding aziridine followed a time
      course similar to the attenuation of cytochrome P450c11 inhibition. It was
      concluded that the aziridine precursor. Compound A, rather than aziridine itself,
      was the inhibiting agent of sheep adrenal P450c11. Addition of sheep and rat
      plasma prevented the attenuation of the effect of Compound A on the spectral
      properties of cytochrome P450c11. Subsequent ES-MS analysis indicated that
      Compound A was stabilized in plasma by sex hormone binding globulin and
      corticosteroid binding globulin. These results suggest a mechanism whereby
      natural plant products, which are highly reactive and unstable in vitro, can be
      stabilized by binding to plasma proteins, and so remain biologically active in
      vivo.

PMID- 9037252
TI  - Human K562 transfectants expressing high levels of reduced folate carrier but
      exhibiting low transport activity.
AB  - A human reduced folate carrier (hRFC) cDNA was transfected into transport
      deficient K562 cells to circumvent complications that may result from carrier
      expression in a heterologous mammalian species. Relative to wild-type cells, hRFC
      transcript levels were increased 11- and 19-fold, respectively, in the K43-6 and
      K43-1 transfectants. Although photoaffinity labeling of hRFC protein revealed
      similar increases of 15- and 19-fold, respectively, only a 2-fold enhancement in
      methotrexate (Mtx) transport was observed. This suggests that only a small
      portion of the cDNA-encoded hRFC protein is actively engaged in membrane
      transport. Kinetic analysis of [3H]Mtx transport indicated that K43-6 cells
      exhibited a similar affinity (Kt) but an increased Vmax (1.7-fold) when compared
      with K562 cells. The restored transport was similar to that of wild-type cells in
      its capacity to be trans-stimulated by intracellular folates and in its
      sensitivity to competitive transport inhibitors (1843U89, bromosulfophthalein,
      folic acid, leucovorin, and ZD1694) and to irreversible inhibition by N
      hydroxysuccinimide-methotrexate. Further, deglycosylated photoaffinity-labeled
      hRFC protein in both K562 and K43-6 cells migrated at approximately 65-70 kDa on
      SDS-gels, consistent with the molecular mass from the predicted amino acid
      sequence. These data further establish that the expression of hRFC, alone, is
      sufficient to confer transport properties typical of the "classical" hRFC.
      However, the discrepancy between the stoichiometry of carrier expression and
      transport activity implies that membrane translocation of bound substrate may be
      regulated by additional undefined mechanisms.

PMID- 9037253
TI  - Isolation and expression of a mouse CB1 cannabinoid receptor gene. Comparison of
      binding properties with those of native CB1 receptors in mouse brain and N18TG2
      neuroblastoma cells.
AB  - The predominant animal model in which the pharmacology of cannabinoids is studied
      is the mouse. Nonetheless, the structure and functional expression of the mouse
      cannabinoid receptor (CB1) gene have not been reported. We have cloned and
      expressed the gene for the mouse CB1 receptor and compared its properties with
      those of native mouse CB1 receptors in brain and N18TG2 neuroblastoma cells. The
      mouse CB1 gene was isolated from a mouse 129 strain genomic library. Sequence
      analysis of a 6-kb BamHI fragment of the mouse CB1 genomic clone indicates 95%
      nucleic acid identity between mouse and rat (99.5% amino acid identity) and 90%
      nucleic acid identity (97% amino acid identity) between mouse and human.
      Examination of the 5' untranslated sequence of the mouse CB1 genomic clone
      revealed a splice junction site approximately 60 bp upstream from the translation
      start site, indicating the possibility of splice variants of the CB1 receptors.
      The coding region of the mouse CB1 receptor was stably expressed in 293 cells,
      and binding by [3H]SR 141716A and [3H]CP-55,940 was determined. The Bmax and Kd
      values obtained with [3H]SR 141716A (921 +/- 58 fmol/mg and 0.73 +/- 0.13 nM,
      respectively) were similar to those of native mouse CB1 receptors in brain (Bmax
      of 1.81 +/- 0.44 pmol/mg, Kd of 0.16 +/- 0.01 nM) and N18TG2 cells (Bmax of 197
      +/- 29 fmol/mg, Kd of 0.182 +/- 0.08 nM). The mouse CB1 receptor genomic clone
      will be a useful tool for studying the function and regulation of the CB1
      receptor in mice.

PMID- 9037254
TI  - Characterization of recombinant human liver dehydroepiandrosterone
      sulfotransferase with minoxidil as the substrate.
AB  - Biotransformation of xenobiotics and hormones through sulfate conjugation is an
      important metabolic pathway in humans. The activation of minoxidil, an
      antihypertensive agent and hair growth stimulator, by sulfation (sulfonation) is
      carried out by more than one sulfotransferase. Initially only the thermostable
      form of phenol sulfotransferase was thought to catalyze minoxidil sulfation. We
      document in this report the new finding that human liver dehydroepiandrosterone
      sulfotransferase (DHEAST), an hydroxysteroid sulfotransferase distinct from
      phenol sulfotransferases, also catalyzes the reaction. To characterize more
      precisely the activity of DHEA ST toward minoxidil, we used COS-1 cells to
      express DHEA ST from a human liver cDNA clone. The apparent Km values for
      minoxidil and [35S]3'-phosphoadenosine-5'-phosphosulfate were 3.9 mM and 0.13
      microM, respectively. The 50% inactivation temperature of the COS-expressed
      enzyme was 42 degrees, and the IC50 value for 2,6-dichloro-4-nitrophenol was 1.4
      x 10(-4) M. Both the thermal stability behavior and response to DCNP were similar
      when the cDNA encoded DHEA ST was assayed with DHEA or minoxidil as a substrate.
      NaCl led to a greater activation of the cDNA expressed DHEA ST when assayed with
      DHEA (2.5-fold) than when the same preparation was assayed with minoxidil (1.4
      fold). These data indicate that DHEA ST catalyzes the sulfate conjugation of
      minoxidil: DHEA ST activity present in the human gut and liver would be expected
      to add to the overall sulfate conjugation of orally administered minoxidil. Thus,
      DHEA ST activity must be considered when determining the human tissue
      sulfotransferase contribution to minoxidil sulfation.

PMID- 9037255
TI  - pH dependence of methotrexate transport by the reduced folate carrier and the
      folate receptor in L1210 leukemia cells. Further evidence for a third route
      mediated at low pH.
AB  - F2-MTX'A is an L1210 leukemia cell line with a functional detect in the reduced
      folate carrier and high level expression of folate receptor beta. The pH
      dependence of methotrexate (MTX) influx by folate receptor beta in F2-MTX'A cells
      was characterized and compared with that of the reduced folate carrier in
      parental L1210 cells. MTX influx by folate receptor beta had a pH optimum of 6.5,
      whereas influx mediated by the reduced folate carrier showed a pH optimum of 7.5.
      Increased folate receptor beta-mediated MTX influx at pH 6.5 relative to pH 7.5
      was accompanied by a 5-fold increase in binding affinity of the receptor for MTX
      without a change in the number of binding sites. At pH 6.2, approximately 24% of
      MTX influx in F2-MTX'A cells proceeded by another mechanism. This transport route
      became active at pH < 7.5, operated optimally at pH 6.0 to 6.5, and, unlike
      folate receptor beta-mediated MTX influx, was insensitive to the presence of low
      levels of folic acid (100 nM). MTX influx by the low pH system showed
      saturability, with a Ki of 5.3 microM and a Vmax of 1.53 nmol/g dry wt/min, was
      energy dependent, was inhibited by sulfobromophthalein with a Ki of 148 microM,
      and had similar relative affinities for folic acid, leucovorin, and 5
      methyltetrahydrofolate. Influx of 5-methyltetrahydrofolate was also mediated by
      this route. The data provide further confirmatory evidence for an MTX influx
      route in F2-MTX'A cells, optimal at low pH and distinct from the reduced folate
      carrier or the folate receptor.

PMID- 9037256
TI  - Gastrointestinal absorption of insulin-like growth factor in the mouse in the
      absence of salivary insulin-like growth factor binding protein.
AB  - Based on previous observations of the presence of both insulin-like growth
      factors I and II (IGF-I and IGF-II) in murine saliva (kerr et al., Biochem
      Pharmacol 49: 1521-1531, 1995), the saliva from BALB/c and Non-obese diabetic
      (NOD) mice was examined for the presence of insulin-like growth factor binding
      proteins (IGFBPs). Using a western-blot type ligand binding assay with 125I
      labeled IGF-I, a series of binding proteins with molecular masses (M), between 25
      and 45 kDa were detected in the sera, but not saliva, from both BALB/c and
      diabetic NOD mice. In the diabetic NOD mice, there were detectable changes in the
      concentrations of several of the IGFBPs relative to BALB/c mice. Using specific
      antibody to the binding proteins, one of these was identified as IGFBP-2. Gavage
      administration of [125I]IGFI indicated substantial uptake from the
      gastrointestinal tract and significant tissue distribution. There was an increase
      in serum concentrations of radiolabeled IGF-I in diabetic NOD mice over that in
      BALB/c mice but less recovered from most of the tissues. Intact 125I-labeled IGF
      I was extracted and purified from various tissues, following gavage, and shown to
      retain biological activity. Thus, the uptake of biologically active IGFs from
      saliva would appear to take place independently of specific binding proteins.

PMID- 9037257
TI  - Antagonism of estrogen receptor and calmodulin association by antiestrogens is
      not dependent on an interaction with calmodulin.
AB  - Previously, two antiestrogens estradiol derivatives (3 and 4) bearing the basic
      side chain of tamoxifen were shown to impede the binding of the estrogen receptor
      (ER) to calmodulin (CaM)-Sepharose. In this study, the interaction of these and
      related compounds with calmodulin was examined using the cyclic AMP
      phosphodiesterase (cAMP-PDE) assay. Neither of the steroids gave any significant
      inhibition of the calmodulin dependent cAMP-PDE activity up to a final
      concentration of 20 microM. For comparison, tamoxifen and nafoxidine produced
      IC50 values of 6.7 microM +/- 1.0 and 7.4 microM +/- 1.1, respectively. In
      addition, a comparison was made of the activity of some triphenylethylene
      derivatives against CaM dependent cAMP-PDE and the ER-CaM Sepharose assays, but
      no relationship was observed. Overall, these results demonstrate that inhibition
      of the ER-CaM association by various steroidal and triphenylethylene
      antiestrogens does not relate to antagonism of calmodulin function or their
      binding affinity for the estrogen receptor.

PMID- 9037258
TI  - Chemosensitization of cancer cells by the staurosporine derivative CGP 41251 in
      association with decreased P-glycoprotein phosphorylation.
AB  - The multidrug resistance (MDR) phenotype of cancer cells often correlates with
      the level and activity of protein kinase C (PKC). We studied the ability of the
      staurosporine derivative PKC inhibitor CGP 41251 to reverse the MDR phenotype in
      MCF-7 human breast carcinoma and CT-26 murine colon adenocarcinoma cells and
      their doxorubicin (DXR)-selected MDR variants. Nontoxic concentrations of CGP
      41251 significantly enhanced the cytotoxic properties of DXR, actinomycin D,
      vinblastine, and vincristine but not those of 5-fluorouracil. CGP 41251 increased
      intracellular concentrations of [14C]DXR but did not cause significant
      differences in P-glycoprotein (P-gp) expression. Pretreatment of MCF-7adr cells
      with phorbol 12-myristate 13-acetate reduced the CGP 41251 mediated intracellular
      accumulation of [14C]DXR. At concentrations that induced drug uptake, CGP 41251
      significantly decreased the level of P-gp phosphorylation in the cells but did
      not compete with [3H]azidopine for photoaffinity labeling of P-gp. These data
      provide evidence that CGP 41251 reverses the MDR phenotype by modulating the
      phosphorylation of P-gp and/or other PKC substrates critical to the maintenance
      of the MDR phenotype.

PMID- 9037259
TI  - Effects of formaldehyde vapor on the nasal cavity and lungs of F-344 rats.
AB  - Histopathological and biochemical examinations of the nasal cavity and lungs of
      rats inhaling 145.6 ppm (high-dose) or 15.0 ppm (low-dose) formaldehyde vapor for
      6 h revealed dose-related damage. The contents of non-protein SH groups (NPSH) in
      the nasal mucosa and lung, and lipid peroxide (LPO) in the nasal mucosa were
      decreased, whereas LPO was increased in the lung. The contents of triglyceride in
      the lung tissue and lavage, and free cholesterol in the lung were decreased,
      providing evidence of a suppression of surfactant production. Exposure-related
      changes in the nasal turbinates, trachea, and lung included hyperkeratosis of the
      squamous epithelium, increased secretion, and desquamation of ciliated and
      mucosal cells. Under the present experimental conditions, 145.6 ppm formaldehyde
      vapor was found to strongly affect the exposed tissues. Changes in lipid peroxide
      were dependent on the level of exposure.

PMID- 9037260
TI  - Reproductive and developmental toxicity studies of toluene. II. Effects of
      inhalation exposure on fertility in rats.
AB  - Male and female Sprague-Dawley rats were exposed to toluene vapor at 600 and 2000
      ppm for 6 h/day, and effects on their fertility were investigated. Females were
      exposed from 14 days before mating until day 7 of gestation. Males were exposed
      for a total of 90 days, including the mating period; treatment was begun 60 days
      before pairing, and toxicity with respect to testicular and reproductive
      functions was examined. In females of the 2000 ppm-treated group, salivation and
      lacrimation that may have been caused by CNS depression were observed starting 20
      days after exposure. Although no abnormalities were seen in mating behavior or
      fertility, fetal mortality and the number of dams with dead fetuses increased in
      the 2000 ppm group. In the males exposed to 2000 ppm toluene for 90 days, an
      increase in kidney weights and a decrease in thymus weights were observed.
      Basophilic changes and necrosis of kidney tubules were greater at the higher
      exposure level. Additionally, decreases in the weights of the epididymides and
      spermatic count were observed, indicating toxicity of toluene to the male
      reproductive system in vivo for the first time. In conclusion, embryo-fetal toxic
      effects were apparent in female rats exposed to toluene before and during the
      early stage of pregnancy. Subacute exposure to a high level (2000 ppm) of toluene
      vapor elicited mild toxic changes in the kidneys, thymus, and reproductive organs
      of males. Toxic effects on fertility and reproduction were thus demonstrated not
      only in females but also in males exposed to toluene vapor in the present study.

PMID- 9037261
TI  - Biochemical and genetic interactions of two commercial pesticides with the
      monooxygenase system and chlorophyllin.
AB  - Two commercial preparations of atrazine and zineb were tested on a diploid D7
      strain of the yeast Saccharomyces cerevisiae using cells from logarithmic growth
      phase (with a high level of cytochrome P-450) and from stationary growth phase.
      The compounds induced marked increases of both gene conversion and point mutation
      frequencies in the logarithmic phase cells, while in the stationary phase no
      genotoxic effect was observed. The results obtained employing TA98 and TA100
      strains of Salmonella typhimurium (Ames test) confirmed that neither atrazine nor
      zineb were mutagenic. The interaction between zineb and chlorophyllin, a known
      antimutagen in several biological systems, has been evaluated in yeast cells from
      logarithmic growth phase. The results showed that chlorophyllin seems to have a
      protective role against the genotoxic effects of zineb. The in vivo effects on
      cytochrome P-450 content (Cyt. P-450) and on monooxygenase activities were
      examined in hepatic microsomes of induced animals (rat, pig, and rabbit) 24 hrs
      after acute treatment. The results obtained with atrazine showed that it caused
      different effects in the three animal species. Preliminary data with zineb
      indicated that it can act both as an inducer or as an inhibitor of the
      monooxygenase system, depending on the dose used.

PMID- 9037262
TI  - Cytogenetic biomonitoring of pesticide-exposed farmers in central Italy.
AB  - The frequency of sister chromatid exchanges (SCE) and micronuclei in peripheral
      blood lymphocytes was evaluated in 48 agricultural workers and 50 control
      subjects living in central Italy. No difference in SCE frequency was found
      between the control and the exposed populations with respect to age, smoking
      habits, and duration of exposure, although smokers, both farmers and controls,
      had a higher SCE frequency than nonsmokers. However, the comparison of
      proliferative rate index values found in the two groups revealed a significant
      decrease in the activation capability of lymphocytes in the pesticide-exposed
      workers, probably related to the toxic properties of chemicals to which the
      farmers were exposed. On the contrary, the analysis of micronuclei frequency
      indicated that there were differences between the exposed and control subjects
      with respect to smoking habits, age, and duration of exposure. Our results
      indicate that, in the study population occupationally exposed to a complex
      mixture, including insecticides, fungicides, and herbicides, there is clear,
      although slight, evidence of clastogenic activity in peripheral blood lymphocytes
      but no corresponding effects on SCE induction. Moreover, our data show clear
      evidence of cell proliferation delay relatable to chemical compounds used in
      agriculture.

PMID- 9037263
TI  - Effect of hexavalent chromium on drug-metabolizing enzymes in male domesticated
      rabbits.
AB  - We studied the effect of chromium on the drug-metabolizing enzymes (DME) in male
      New Zealand white rabbits, Oryctolagus cuniculus, with and without pretreatment
      with phenobarbitone (PB) and promethazine (PM). The activities of cytochrome P
      450 (183%), aniline hydroxylase (ANH, 265%), acetanilide hydroxylase (ACH, 160%),
      benzphetamine demethylase (BD, 112%), aminopyrine demethylase (AD, 97%), N,N,
      dimethyl aniline demethylase (DAD, 72%), and cytochrome-c-reductase (100%) were
      increased after PB treatment. The activities of cytochrome b5 and N,N,-dimethyl
      aniline N-oxide (DAO) were, however, decreased 79% and 47%, respectively. Most of
      the DME remained unaffected after PM treatment except for the increase in ANH
      (55%), ACH (56%), and BD (16%). Potassium dichromate administered to rabbits at a
      dose of 8 mg/kg body weight/day for 5 days resulted in an increase in the
      activities of ANH (108%), BD (76%), AD (25%), and DAD (49%), while that of
      cytochrome b5 and DAO were inhibited 81 and 77%, respectively. There was no
      effect on the activities of cytochrome P-450, ACH, and cytochrome-c-reductase.
      Chromium, administered to PB-pretreated animals decreased the activities of ANH
      (41%), ACH (35%), BD (34%), AD (30%), DAD (51%), cytochrome-c-reductase (72%),
      and DAO (62%). Other enzymes remained unaffected. When administered to PM
      pretreated animals, the activities of ANH, BD, AD, and DAD increased 34, 69, 24
      and 54%, respectively, whereas activities of cytochrome b5 and DAO were decreased
      96 and 68%, respectively. All other DME remained unaffected.

PMID- 9037264
TI  - Effects of vitamin E on the blastogenic response of splenocytes and lipofuscin
      contents in the hearts and brains of aged mice.
AB  - Semipurified diets containing 30 or 500 ppm of dl-alpha-tocopherol (VE) were fed
      for 12 weeks to young (3-month-old) and old (20-month-old) Swiss mice. We
      measured the blastogenic response of splenocytes, the serum VE, and the
      lipofuscin levels in brains and hearts. We found that old mice fed with 500 ppm
      VE diet had a significantly higher serum VE level and blastogenic response of
      splenocytes to concanavalin-A (ConA) and lipopolysaccharide (LPS) than those fed
      with 30 ppm VE diet (p < 0.01). However, the lipofuscin level in the brains and
      hearts of aged mice declined substantially with the VE supplementation (heart: p
      < 0.001, brain: p < 0.05). Furthermore, the effects of dietary VE on the serum VE
      and tissue lipofuscin content in aged mice were much more obvious than in the
      young animals.

PMID- 9037265
TI  - Psychodynamic aspects of smoking cessation among physicians.
AB  - After approximately 10 years of research on smoking habits with an emphasis on
      prevention and dishabituation, we focused on the training of teachers and general
      practitioners. A fairly wide-ranging inquiry within the Communaute francaise de
      Belgique was conducted among nearly 2000 doctors. The study showed that the
      proportion of smokers, although lower than the average in the general population,
      was higher among the doctors than other socio-professional categories. A
      comparison of the results registered in 1983 and 1991 revealed a decrease in the
      number of smokers and an increase in the number of non-smokers (those who have
      never smoked). This change stemmed largely from a sharply lower smoking rate
      among young doctors. These findings impelled us to study the resistance to
      dishabituation among doctors who smoked. The inquiry was comprised of non
      authoritative, Rogerian-style talks that enabled us to isolate a number of
      motivating factors and some rather typical defense mechanisms that, until
      recently, went partly unnoticed. The denial, indeed the placation, of anxieties
      in the medical profession fostered by the constant confrontation with illness and
      the challenge of and victory over death apparently plays a crucial role, albeit
      on the unconscious plane.

PMID- 9037266
TI  - Role of PCR in the diagnosis and management of CMV in solid organ recipients:
      what is the predictive value for the development of disease and should PCR be
      used to guide antiviral therapy?

PMID- 9037267
TI  - Preemptive therapy: Epstein-Barr virus.

PMID- 9037268
TI  - Cytomegalovirus hyperimmune gammaglobulin downregulates in vitro T-cell
      responses.

PMID- 9037269
TI  - Defining an optimal regimen for cytomegalovirus prophylaxis in organ transplant
      recipients.

PMID- 9037270
TI  - Combination protocols for prevention of CMV disease in the high risk transplant
      patient.
AB  - Overall, the results seen in this study are encouraging. In this high-risk group
      of patients where the expected disease rate would normally be at least 55% to 60%
      without prophylaxis, a combination protocol of GCV, ACV, and CMVIG limited the
      rate of disease to 19%. When disease occurred, it was generally mild and easily
      treatable. While stratification of patients according to organ transplant group
      and donor/recipient serology may help to better define future protocol designs,
      the combination strategy used in this study has clearly demonstrated its
      usefulness in the high-risk transplantation population.

PMID- 9037271
TI  - How effective is oral ganciclovir?

PMID- 9037272
TI  - Cytomegalovirus infection in seromismatched lung transplant recipients with and
      without prophylaxis with CMV immunoglobulin.

PMID- 9037273
TI  - Meta-analysis of CMVIG studies for the prevention and treatment of CMV infection
      in transplant patients.

PMID- 9037274
TI  - Electrovaporization of the prostate: durable modality or passing fad?

PMID- 9037275
TI  - Laser prostatectomy is a safer, better operation than electrovaporization of the
      prostate.

PMID- 9037276
TI  - Hypospadias update.

PMID- 9037278
TI  - Use of p53 in the diagnosis of upper-tract transitional cell carcinoma.
AB  - OBJECTIVES: To assess the usefulness of p53 staining of cytology specimens
      obtained ureteroscopically in the diagnosis of upper-tract transitional cell
      carcinoma (TCC). METHODS: We collected specimens from 43 patients undergoing a
      total of 50 ureteroscopic procedures for a variety of indications, including the
      diagnosis of TCC. Specimens were obtained by direct biopsy with forceps or basket
      whenever possible. We examined specimens for evidence of TCC by cytospin as well
      as cell block for any visible fragments. Each specimen was then stained for
      overexpression of p53 by immunohistochemical staining, and the degree of staining
      was graded. Eight patients subsequently underwent nephroureterectomy; the
      pathologic specimens were stained for p53 and compared with the cytology results.
      RESULTS: Staining for p53 was positive in specimens from 36 of 50 procedures,
      including all 28 with ureteroscopic or cytologic evidence of TCC (P < 0.0001). By
      contrast, cytology accurately diagnosed only 23 of the 28. Specimens from all 14
      procedures that were negative also stained negative for p53. Specimens from all 8
      procedures with no tumor seen and atypical cytology stained positive for p53; 4
      of 5 patients with adequate follow-up have had a tissue diagnosis of TCC at that
      site. Overall, 35 of the 36 specimens that stained positive for p53 were obtained
      from patients with some history of TCC (P < 0.0001). No significant association
      could be found between degree of staining and grade (P = 0.3034). The degree of
      staining of ureteroscopic biopsy specimens was identical to that of the
      nephroureterectomy specimen in 6 of 8 cases. CONCLUSIONS: p53 nuclear protein
      staining of cytology specimens obtained ureteroscopically appears to correlate
      well with the presence of upper-tract urinary TCC. Further study is needed to
      determine if it can provide a definitive diagnosis in cases with indeterminate
      cytologic findings.

PMID- 9037277
TI  - Adenovirus-mediated suicide gene therapy for experimental bladder cancer.
AB  - OBJECTIVES: To determine the feasibility, safety, and efficacy of suicide gene
      therapy using adenoviral-mediated herpes simplex virus thymidine kinase gene (HSV
      tk) and the prodrug ganciclovir (GCV) in a murine model of human transitional
      cell carcinoma. METHODS: We used a replication-defective adenoviral construct
      containing the beta-galactosidase gene (ADV/Rous sarcoma virus [RSV]-beta-gal) as
      a control or ADV/RSV-tk as the therapeutic vector under the transcriptional
      control of the RSV long-terminal repeat promoter. Transduction efficiency was
      assessed in vitro by infection of MBT-2 cells with ADV/RSV-beta-gal at various
      multiplicities of infection (MOI) utilizing 5-bromo-4-chlor-3-indolyl-beta-D
      galactoside (X-gal) staining. Sensitivity of MBT-2 cells to the therapeutic
      vector was determined after infection with ADV/RSV-tk with or without GCV.
      Subcutaneous tumors were established in syngeneic C3H/He female mice with 5 x
      10(5) MBT-2 cells. Optimal dosing of ADV/RSV-tk was determined by direct
      percutaneous tumor injection with increasing viral doses and treatment with GCV.
      Treatment efficacy, long-term survival, and toxicity were determined in separate,
      similar, controlled experiments. RESULTS: In vitro studies indicated greater than
      95% transduction 96 hours after inoculation at an MOI of 3000 and a greater than
      95% cell death rate with RSV-tk + GCV at an MOI of 61 or greater. In vivo
      experiments demonstrated an optimal viral dose of 3 x 10(8) plaque-forming units
      (pfu) and a greater than fourfold reduction in tumor growth for the animals
      treated with ADV/RSV-tk compared with control animals (P = 0.0013). Toxicity was
      limited to histologic evidence of hepatitis with ADV/RSV-tk doses greater than 3
      x 10(8) pfu + GCV. Long-term survival of treatment animals was significantly
      increased over that of control animals (59%, P = 0.0001). CONCLUSIONS: ADV/RSV-tk
      with GCV treatment results in efficient gene transfer in vitro and provides
      effective therapy in experimental murine bladder cancer by significantly
      inhibiting tumor growth and improving host survival.

PMID- 9037279
TI  - Results at 43 months' follow-up of a double-blind, randomized, prospective
      clinical trial using intravesical interferon alpha-2b in the prophylaxis of stage
      pT1 transitional cell carcinoma of the bladder.
AB  - OBJECTIVES: To assess the intravesical efficacy of 60 million units of interferon
      (IFN) alpha-2b in preventing recurrences of Stage pT1 transitional cell carcinoma
      of the bladder, as well as to assess its local and systemic toxicity. METHODS: A
      total of 90 patients were included in a double-blind, randomized, prospective
      clinical trial and divided into two groups of 45 patients. After complete
      transurethral resection, 60 million units IFN alpha-2b was instilled in one
      group; in the other, double-distilled water was used. The therapeutic regimen
      consisted of weekly instillation for 12 weeks, followed by once-monthly
      instillation until patients had completed 1 year of treatment. RESULTS: Only 78
      patients were evaluable. After 12 months of follow-up, the relapse rate was 28.2%
      (11 of 39) for the IFN group and 35.8% (14 of 39) for the control group (P = NS).
      After 43 months (range 9 to 67), relapse rates were 53.8% (21 of 39) and 51.2%
      (20 of 39), respectively (P = NS). Progression, mortality, and local or systemic
      toxicity were similar in both groups. Flu-like syndrome was not reported.
      CONCLUSIONS: At the dose used in this study, IFN alpha-2b proved ineffective in
      the prophylaxis of Stage pT1 transitional cell carcinoma of the bladder compared
      with a control group. Toxicity was virtually absent.

PMID- 9037281
TI  - Urodynamic and clinical effects of terazosin therapy in symptomatic patients with
      and without bladder outlet obstruction: a stratified analysis.
AB  - OBJECTIVES: To evaluate clinical and urodynamic changes in patients with and
      without bladder outlet obstruction (BOO) and to compare the clinical and
      urodynamic results of terazosin treatment between patients with and without BOO.
      METHODS: In a prospective study, 97 patients who completed a full screening
      program including urodynamic investigation with pressure-flow study analysis
      started treatment with terazosin. A total of 60 patients completed 6 months of
      treatment and were re-evaluated with International Prostate Symptom Scores
      (IPSS), uroflowmetry, and urodynamic investigation with pressure-flow study
      analysis. Patients were stratified using the linear passive urethral resistance
      relation (lin-PURR) classification according to Schafer. Patients with a lin-PURR
      of 3 or more were classified as patients with BOO and patients with a lin-PURR of
      2 or less were classified as patients without BOO. The clinical and urodynamic
      changes within and between the groups with and without BOO were evaluated.
      RESULTS: Terazosin resulted in significant symptomatic relief (9 points on the
      IPSS scale; P < 0.01) and a significant improvement of free urinary flow (3.0
      mL/s; P < 0.01). In patients with BOO, a statistically significant improvement of
      all urodynamic obstruction variables (P < 0.01) was shown. In patients without
      BOO, a significant improvement of free urinary flow (4.4 mL/s; P < 0.01), a
      statistically significantly improved bladder capacity (increase of 70 mL; P =
      0.01), and no statistically significant changes in urodynamic obstruction
      variables (P > 0.05) were shown. Patients with a hypoactive detrusor were more
      prone to early dropout. When comparing the changes of symptoms (P = 0.89),
      quality of life (P = 0.85), and the number of patients with improvements of free
      uroflow of at least 30% (P = 0.15), there appeared to be no significant
      difference between the groups with and without BOO. CONCLUSIONS: Although there
      is a statistically significant difference in urodynamic response to terazosin
      treatment between patients with and without BOO, we cannot recommend the use of
      pressure-flow studies in the selection of patients for terazosin treatment
      because the clinical results of treatment appear not to be significantly
      different between patients with and without BOO. It seems more useful, and
      certainly less expensive and less invasive, to start alpha 1-blocker therapy if,
      on clinical grounds, the urologist considers the patient to be a candidate for
      alpha 1-blocker therapy, and to continue therapy in those who respond.

PMID- 9037280
TI  - Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced
      testosterone transdermal system.
AB  - OBJECTIVES: This study examined the effects of testosterone replacement using a
      nonscrotal testosterone transdermal (TTD) system on prostate size and prostate
      specific antigen (PSA) levels in hypogonadal men. METHODS: As part of an open
      label, multicenter study, prostate volume as measured by transrectal ultrasound
      and PSA were assessed in 29 hypogonadal men during treatment with intramuscular
      testosterone enanthate (+TE), followed by 8 weeks of androgen withdrawal (-T),
      and then during 1 year of therapy with Androderm Testosterone Transdermal System,
      a nonscrotal permeation-enhanced TTD system (+TTD). RESULTS: Mean prostate volume
      decreased significantly from the +TE period (17 g) compared with the -T period
      (14 g) (P < 0.001). Prostate volume increased significantly from the -T period
      compared with the +TTD period (18 g) (P < 0.001). Maximum prostate size,
      comparable to that measured during +TE (P = 0.125), was reached by month 3 of
      +TTD therapy; prostate volume did not increase further during the remaining 9
      months of +TTD therapy. Prostate volume correlated with age (P < 0.01) during all
      three periods of observation (+TE: r = 0.69; -T: r = 0.64; and +TTD: r = 0.55).
      No patient developed symptomatic benign prostatic hyperplasia during the
      treatment period. PSA levels decreased during androgen withdrawal compared with
      levels measured during +TE treatment (P < 0.001) and rose with resumption of
      androgen therapy with TTD (P < 0.006). However, PSA levels during +TTD
      replacement remained significantly lower (P < 0.001) than during +TE replacement.
      CONCLUSIONS: Physiologic testosterone replacement in hypogonadal men was achieved
      using the TTD system. Prostate size during therapy with TTD was comparable to
      that reported for normal men. In these men treated with TTD, PSA levels were also
      within the normal range.

PMID- 9037282
TI  - Health-related quality of life among patients with metastatic prostate cancer.
AB  - OBJECTIVES: To assess and compare the quality of life of men with advanced
      prostate cancer who are in remission receiving treatment with a luteinizing
      hormone-releasing hormone (LHRH) agonist and flutamide or who are in progression.
      METHODS: We conducted a cross-sectional survey to measure health-related quality
      of life in a cohort of 113 patients with metastatic prostate cancer, 60 in
      remission and 53 with disease progression, using a battery of questionnaires,
      including the European Organization for Research and Treatment of Cancer Quality
      of Life Questionnaire-C30, the Medical Outcomes Study Short Form Health Survey SF
      36, and a prostate cancer-specific module. RESULTS: Patients in remission
      receiving an LHRH agonist and flutamide reported a significantly better quality
      of life compared with patients with disease progression (P < 0.011). Men with
      hormone-sensitive cancer had significantly less bodily pain, more vitality, more
      social interactions, and better mental health than patients with hormone
      resistant disease. No differences were noted between the two groups concerning
      treatment-related problems such as diarrhea, constipation, urinary symptoms,
      sexual function, sexual satisfaction or hot flashes, although men in remission
      tended to rate each of these items more favorably than did men with disease
      progression. Men in remission have a health-related quality of life that is
      similar to an equivalent norm for men in the United States general population as
      compared with men with disease progression, who demonstrate significant
      compromise in all domains measured. CONCLUSIONS: Patients in remission receiving
      an LHRH agonist and flutamide have a quality of life that is indistinguishable
      from a matched male population without prostate cancer and a quality of life
      significantly better than that of men with androgen-resistant disease. Among
      patients who respond to total androgen ablation, flutamide and an LHRH agonist
      provide significant, measurable benefits to recipients independent of any
      possible improvement in longevity.

PMID- 9037283
TI  - Treatment considerations for persons with metastatic prostate cancer: survival
      versus out-of-pocket costs.
AB  - OBJECTIVES: Treatment decisions for metastatic prostate cancer require the
      consideration of factors such as survival, quality of life, costs of care, and
      toxicities. In this study, we queried physicians who had extensive experience
      with prostate cancer about features of metastatic prostate cancer, patients'
      quality of life, and factors influencing their decision to prescribe flutamide.
      METHODS: Data were gathered through physician surveys and focus group
      discussions. Demographic information on the physicians and their patients was
      collected. Physicians made assessments of five health states related to
      metastatic prostate cancer, based on the time trade-off technique, and on the
      desirability of flutamide, based on average expected improvement in survival free
      of progressive disease, side effects, and drug cost. RESULTS: Physicians were
      internally consistent in their judgments of the factors most important to quality
      of life for individuals with metastatic prostate cancer. Physicians considered
      bone pain and weight loss/anorexia the most important factors. Physicians who
      cared for a higher proportion of older persons or Medicare recipients rated each
      scenario as less undesirable than did physicians with a lower proportion of these
      patients. Out-of-pocket cost was the major factor predicting whether a physician
      would prescribe flutamide. Physicians working for health maintenance
      organizations were more likely to prescribe flutamide but were more sensitive to
      out-of-pocket costs than were other physicians. CONCLUSIONS: Physicians-varied in
      their perceptions of quality of life for persons with metastatic prostate cancer
      and in their willingness to prescribe flutamide. These perceptions and
      prescribing preferences are strongly influenced by factors other than health
      status or specific health benefits. In deciding to prescribe flutamide, concerns
      over out-of-pocket expenditures loom large for most clinicians. It would be
      important to know the degree to which these concerns are shared by patients and
      whether prescribing preferences differ for Medicare managed-care patients who
      have pharmaceutical benefits.

PMID- 9037284
TI  - Prospective assessment of incontinence after radical retropubic prostatectomy:
      objective and subjective analysis.
AB  - OBJECTIVES: To assess prospectively-using pad test and questionnaire-the rate and
      degree of incontinence after radical retropubic prostatectomy, to analyze factors
      that may predispose individuals to postoperative incontinence, and to assess the
      impact of incontinence on patient lifestyle. METHODS: Fifty-one consecutive
      patients were assessed at 3-month intervals for 1 year after radical retropubic
      prostatectomy. Patients were objectively assessed using a 1-hour pad test and
      subjectively assessed by questionnaire. Incontinence was graded objectively
      according to the change in weight of the pad at 1 hour and subjectively by the
      number of pads used per day. Lifestyle modifications were assessed by
      questionnaire at 12 months. A number of variable factors were studied to assess
      risk factors for postoperative incontinence. RESULTS: Continence continued to
      improve up to 12 months. At 12 months, pad testing revealed 84% of patients were
      dry, 6% were mildly incontinent. 6% were moderately incontinent, and 4% were
      severely incontinent. Questionnaire assessment revealed 80% wore no pad, 14% had
      mild incontinence, 4% had moderate incontinence, and 2% had severe incontinence.
      Pad testing was not as sensitive as the questionnaire for the detection of
      minimal incontinence but was more reliable for moderate and severe levels.
      Patients made lifestyle changes proportional to the level of incontinence. No
      predisposing factor was identified for the development of incontinence after
      radical retropubic prostatectomy. CONCLUSIONS: Significant incontinence after
      radical prostatectomy occurs in as many as 10% of patients. Pad testing provides
      an inexpensive and simple form of objective assessment in patients with
      bothersome incontinence and allows documentation of improvement over time.

PMID- 9037285
TI  - Retrograde leak point pressure for evaluating postradical prostatectomy
      incontinence.
AB  - OBJECTIVES: To evaluate a technique of measuring the retrograde leak point
      pressure (RLPP) for assessing men with postradical prostatectomy stress urinary
      incontinence (SUI). METHODS: We measured RLPP in adult men by retrograde infusion
      of the distal urethra while simultaneously recording intraurethral pressure. The
      reproducibility of this test, and its dependence on urethral infusion rate,
      bladder volume, and anterior urethral catheter position, were evaluated. RLPP and
      abdominal leak point pressure (ALPP) measurements were performed in postradical
      prostatectomy patients. RLPP was compared with ALPP and with severity of
      incontinence determined by pad usage. RESULTS: Repeated RLPP measurements were
      not significantly different and did not change with bladder volume up to half
      capacity or with the location of the catheter in the anterior urethra. The
      differences between RLPP measurements with infusion rates of 2, 4, and 8 mL/min
      were also not significant. Twenty-seven men were evaluated 6 to 108 months after
      surgery. Of these, 22 (81%) demonstrated SUI. Mean RLPP in men without SUI (79.2
      +/- 14 cm H2O) was significantly higher than in men with SUI (51.9 +/- 13 cm H2O,
      P < 0.01). In men with SUI, ALPP and RLPP were significantly correlated, and ALPP
      (49.8 +/- 24 cm H2O) was not significantly different from RLPP (51.9 +/- 13 cm
      H2O) Pad use and RLPP were also significantly related. CONCLUSIONS: RLPP
      measurements are reproducible and simple to perform. The pressure at which
      leakage occurs is easily identifiable as the plateau pressure. RLPP correlates
      significantly with the lowest of multiple ALPP measurements in men with SUI. This
      technique represents a reliable urodynamic alternative for evaluating men with
      postradical prostatectomy SUI.

PMID- 9037286
TI  - Osteitis pubis after periurethral collagen injection.
AB  - Periurethral collagen injection is a relatively new procedure to treat stress
      incontinence. Until now, complications and side effects have been minor and
      transient. We will present the first reported case of osteitis pubis after
      periurethral collagen injection.

PMID- 9037287
TI  - Use of electroejaculation in the treatment of ejaculatory failure secondary to
      diabetes mellitus.
AB  - OBJECTIVES: To describe the experience of two male fertility programs using
      electroejaculation (EEJ) in the management of men with ejaculatory failure
      secondary to diabetes mellitus. METHODS: Twenty-nine EEJ procedures were
      performed in 7 diabetic men with ejaculatory failure. Results were reviewed with
      attention paid to sperm characteristics in both antegrade and retrograde
      specimens as well as pregnancy rates. RESULTS: Retrograde semen specimens
      retrieved from the bladder following EEJ contained a mean of 3444.5 million sperm
      (range 269.2 to 4996 million). Antegrade specimens contained a mean of 698.8
      million sperm (range 226.8 to 1961 million). Mean sperm motility was 4% for
      retrograde specimens (range 0% to 11%) and 7% for antegrade specimens (1% to
      15%). In all but 1 case, semen specimens were used for intrauterine insemination.
      The total number of motile sperm contained in the processed, inseminated
      specimens ranged from 1 to 87.2 million. In 1 case, the sperm obtained through
      EEJ was used in an in vitro fertilization procedure. CONCLUSIONS: EEJ can be
      successfully used to obtain sperm from men with ejaculatory failure due to
      diabetes mellitus. The procedure requires general anesthesia, and pregnancy rates
      after intrauterine insemination with the processed sperm are low. Advanced
      reproductive technologies may offer a feasible alternative, providing higher
      success rates with fewer procedures.

PMID- 9037288
TI  - Sachse urethrotomy versus endoscopic urethrotomy plus transurethral resection of
      the fibrous callus (Guillemin's technique) in the treatment of urethral
      stricture.
AB  - OBJECTIVES: Advances in endoscopic instrumentation and technique have expanded
      the urologist's armamentarium for effective and safe treatment of urethral
      strictures. This prospective study included 80 patients who presented with
      single, iatrogenic, annular strictures of the bulbar urethra. The length of the
      stricture was 1 to 2 cm, with an average of 1.5 cm. METHODS: Patients were
      randomly divided into two groups: group A, 40 patients who underwent direct
      optical endoscopic urethrotomy with a guide catheter via cold-knife incision at
      the 12 o'clock position (Sachse urethrotomy), and group B, 40 patients who
      underwent double direct-optical endoscopic urethrotomy with a guide catheter via
      cold-knife incisions at the 11 and 1 o'clock positions, followed by transurethral
      resection of all scar tissues (Guillemin's technique). The results obtained were
      analyzed and compared at 6 months, 12 months, 24 months, 3 years, and 5 years
      postoperatively by clinical evaluation, uroflowmetry, and retrograde and voiding
      urethrographies. RESULTS: Group A obtained 95% good results at 6 months, 85% at
      12 months, 55% at 24 months, 45% at 3 years, and 25% at 5 years. Group B obtained
      98% good results at 6 months, 95% at 12 months, 90% at 24 months, 80% at 3 years,
      and 70% at 5 years. CONCLUSIONS: The differences between the two groups are not
      significant at 6 and 12 months (P > 0.05). They are statistically significant
      after 24 months, 3 years, and 5 years (P < 0.05).

PMID- 9037289
TI  - Influence of the method of intracavernous injection on penile rigidity: a
      possible pharmacokinetic explanation.
AB  - OBJECTIVES: To study whether the method of intracavernous injection of
      vasodilators has an effect on the clinical outcome and to explain the mechanism
      of possible influence. METHODS: In an open clinical study, penile rigidity after
      bolus injection was compared with rigidity after slow injection in 52 self
      injecting, impotent patients. In 35 volunteers, venous plasma levels of
      intracavernosally injected drugs were followed under different injection
      conditions: slow injection of undiluted drug, slow injection of diluted drug,
      bolus injection, use of a tourniquet, or slow injection followed by squeeze of
      the corpora. RESULTS: Of the 52 patients, 28 reported better penile rigidity
      after a bolus injection than after slow injection of vasodilators. The other 24
      reported no difference in rigidity. Systemic side effects did not occur, but 4
      patients reported local pain after bolus injection. In the 35 volunteers, the
      lowest plasma levels were observed when a tourniquet was used or when a bolus
      injection was performed; the quickest transfer was observed after a slow
      injection of a low volume of the drug. CONCLUSIONS: Better rigidity was observed
      after bolus injection in a majority of the patients using the same dose of
      vasodilators. This could be due to the pharmacokinetic phenomenon of a slower
      drug transfer to the systemic circulatory system after a bolus than after a slow
      injection.

PMID- 9037291
TI  - Plexiform neurofibroma involving the genitourinary tract in children: case
      reports and review of the literature.
AB  - We report extensive genitourinary neurofibroma in two children who presented with
      massive bilateral hydroureteronephrosis and a thick-walled bladder. The best
      radiologic technique to stage the disease and determine treatment is magnetic
      resonance imaging. Management of extensive genitourinary neurofibroma is
      controversial. Based upon our experience and a review of the literature,
      aggressive surgery should be approached cautiously.

PMID- 9037290
TI  - Prostate-specific antigen in men born with bladder exstrophy.
AB  - OBJECTIVES: To determine serum levels of prostate-specific antigen (PSA) in men
      born with bladder exstrophy and to investigate the clinical utility of this test
      in the bladder exstrophy population. METHODS: Ten men aged 19 to 45 years with a
      history of bladder exstrophy underwent digital rectal examination and free and
      total serum PSA determinations. Immunohistochemistry for PSA and prostate
      specific acid phosphatase (PSAP) was performed on archival prostate tissue from 1
      man with bladder exstrophy. RESULTS: Free and total serum PSA levels for all
      patients were measurable and below the upper limit for established age-specific
      reference ranges for normal men. Both PSA and PSAP were detectable by
      immunohistochemistry in prostate epithelial cells of a man with bladder
      exstrophy. CONCLUSIONS: Men born with bladder exstrophy have detectable serum PSA
      levels. However, because prostate cancer in men with bladder exstrophy has not
      been reported, whether PSA will have a clinical role as a serum tumor marker for
      prostate cancer in this population remains to be determined. If so, the PSA
      reference range for men with the exstrophy condition will need to be defined.
      Because prostate histology in men with exstrophy resembles that of normal men,
      careful clinical monitoring for benign and malignant tumors should not be
      overlooked in this particular population.

PMID- 9037292
TI  - Comparison of effects of suture materials on wound healing in a rabbit
      pyeloplasty model.
AB  - OBJECTIVES: To compare the effects of chromic catgut, polyglactic acid,
      polydioxanone (PDS), and polytrimethylene carbonate suture on urothelial healing
      in a rabbit model simulating pyeloplasty. METHODS: Pyeloureterotomies were
      performed on 8-week-old rabbits [12 rabbits (24 renal units) and 3 control
      rabbits] and closed with interrupted 7-0 sutures. At 10 days, 5 weeks, and 12
      weeks postoperatively, we assessed the upper tracts by examining microscopic
      sections of the renal pelvis and upper ureter. Acute and chronic inflammation,
      foreign body reaction, and fibrosis/scar formation were assessed blindly and
      scored from 0 to 4. RESULTS: Histologic evidence of acute and chronic
      inflammation and foreign body reaction was most severe at 10 days and 5 weeks in
      pyeloureterotomies closed with chromic catgut. There was mild inflammation in
      those closed with polyglactic acid at 10 days, but it was minimal in those closed
      with polyglactic acid, PDS, and polytrimethylene carbonate at 5 and 12 weeks.
      Reabsorption of polyglactic acid was complete by 5 weeks, but was incomplete with
      the other three sutures at that time. By 12 weeks, there was persistent suture in
      50% of the renal units closed with polydioxanone and in 100% of those closed with
      polytrimethylene carbonate. No animal developed a renal calculus. CONCLUSIONS:
      Because of the mild inflammatory response and rapid tissue reabsorption of
      polyglactic acid in this animal model, this suture appears to be the best suture
      for pyeloplasty.

PMID- 9037293
TI  - Rupture of a large calyceal diverticulum.

PMID- 9037294
TI  - Three-dimensional computed tomographic angiography of a horseshoe kidney with
      ureteropelvic junction obstruction.

PMID- 9037295
TI  - Ureteral duplication with lower pole ectopia to the vas: a case report of an
      exception to the Weigert-Meyer law.
AB  - We report an unusual case of ureteral duplication with lower-pole ectopia and
      ureterolithiasis, which violates the Weigert-Meyer law. The duplicated ureter
      arose from a lower-pole calyx and drained inferiorly into the ipsilateral vas. A
      presentation of the case is followed by a comparison to the only known similar
      one, reported in 1988. A possible embryologic hypothesis for this anomaly is
      discussed.

PMID- 9037296
TI  - Laparoscopic creation of a catheterizable cutaneous ureterovesicostomy.
AB  - Nephrectomy and creation of a cutaneous ureterovesicostomy for intermittent
      catheterization of the bladder traditionally requires two surgical procedures
      performed through separate incisions. Herein we report completion of these
      procedures using a transperitoneal laparoscopic approach, with the
      ureterovesicostomy stoma created at one of the laparoscopic working ports. The
      clinical course was remarkable for a shortened postoperative hospitalization (48
      hours) with minimal incisional pain, and an excellent long-term result with
      complete bladder emptying and resolution of urinary infections. Laparoscopic
      application of the Mitrofanoff principle for creation of a catheterizable
      cutaneous ureterovesicostomy combines the advantages of both, allowing optimal
      preservation of ureteral vascularity, minimal morbidity, and efficient bladder
      evacuation.

PMID- 9037297
TI  - Primary lymphoma of the bladder: a unique cystoscopic appearance.
AB  - Primary lymphoma of the bladder is a rare disorder that occurs in the fifth to
      seventh decades, with a female preponderance. Although computed tomographic
      scanning is the best diagnostic imaging study, cystoscopic biopsy and
      immunoperoxidase staining are needed to make the diagnosis. Primary lymphoma of
      the bladder has a good prognosis and responds to a variety of therapeutic
      modalities. Throughout the literature, authors have described primary lymphoma of
      the bladder as a submucosal tumor, smooth, nonulcerative, edematous, friable, or
      even hemorrhagic. We present what we believe to be the first photographic image
      of the cystoscopic appearance of primary lymphoma of the bladder.

PMID- 9037298
TI  - Prostate-specific antigen-producing cells in the bone marrow of a patient with
      early-stage prostate cancer.
AB  - This report describes a clinical case that supports the hypothesis that occult
      bone marrow disease may exist even in early-stage and low prostate-specific
      antigen (less than 10 ng/mL) prostate cancer. The concept of adding androgen
      suppression to definitive local therapy in these patients is discussed.

PMID- 9037299
TI  - Fulminant hepatic failure associated with bicalutamide.
AB  - Bicalutamide is a new, nonsteroidal antiandrogen with a favorable toxicity
      profile. We report the first case of fulminant hepatic failure associated with
      its use.

PMID- 9037300
TI  - Juvenile hemangioma of the testis: analysis of expression of angiogenic factors.
AB  - We present a case of juvenile hemangioma of the testis associated with
      hemangiomas of the liver and skin. The testicular hemangioma appeared to progress
      after therapy with interferon alpha-2a (IFN alpha-2a), whereas the liver and skin
      hemangiomas regressed. Analysis of growth factors responsible for proliferation
      of hemangioma revealed that the tumor expressed vascular endothelial growth
      factor but not basic fibroblast growth factor (bFGF), which is reported to be
      inhibited by IFN alpha-2a. This finding suggests that a possible explanation for
      the inadequate efficacy of IFN alpha-2a for testicular hemangioma is a lack of
      bFGF expression.

PMID- 9037301
TI  - Expression of microfibrillar proteins by bovine bladder urothelium.
AB  - OBJECTIVES: To determine the occurrence and potential function of proteins
      composing elastic microfibrils in the developing bovine bladder. METHODS:
      Monospecific antibodies, generated against two well-characterized microfibrillar
      proteins, microfibril-associated glycoprotein (MAGP) and fibrillin-1 (FBN1), were
      used in immunohistochemical analysis of full-thickness frozen sections of fetal
      bovine bladder. The localization of these two antibodies was compared with that
      of anti-type IV collagen antibody. Adjacent serial sections were stained for
      routine light microscopy. Cultured urothelial cells were fixed in 3.7%
      formaldehyde and permeabilized with 0.5% Triton X-100 before immunoanalysis.
      Control reactions used either preimmune serum or a monoclonal antibody to a
      nonmatrix protein. Poly(A+) ribonucleic acid was isolated from cultured
      urothelial cells and subjected to Northern analysis using specific complementary
      deoxyribonucleic acid probes for MAGP and FBN1. RESULTS: Both MAGP and FBN1 are
      expressed by the urothelium and are found in association with the underlying
      basement membrane, as visualized by their co-localization with type IV collagen.
      Furthermore, urothelial cells in culture continue to express both microfibrillar
      proteins. CONCLUSIONS: The developing bovine urothelium expresses major
      microfibrillar protein components. The role of these microfibrils in the
      urothelium remains to be determined, but they may have an important anchoring
      function.

PMID- 9037302
TI  - Correlation of ischemia/reperfusion or partial outlet obstruction-induced
      spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder.
AB  - OBJECTIVES: In the rabbit, both experimental ischemia and partial outlet
      obstruction of the urinary bladder induce similar dysfunctions with regard to the
      contractile responses to both field (neuronal) stimulation and postsynaptic
      receptor stimulation. Circumstantial evidence indicates that the pathologic
      response to both conditions is related to two connected processes-tissue ischemia
      and reperfusion injury-that result in a marked increase in intracellular calcium
      ([Ca2+]i), followed by the activation of the Ca(2+)-dependent neutral protease
      calpain. Calpain activation results in the proteolysis of specific membrane
      proteins, including those of neuronal membranes (resulting in progressive
      denervation of the detrusor) and the sarcoplasmic reticulum Ca(2+)-ATPase
      (SERCA), resulting in the previously reported decrease in SERCA. The current
      study is designed to generate direct support for the theory that both ischemia
      and partial outlet obstruction result in the activation of calpain. METHODS:
      Separate sets of rabbits were subjected to 1 or 2 hours of ischemia, followed by
      reperfusion for different lengths of time, or partial outlet obstruction for
      different lengths of time. We determined the state of calpain activation by
      quantitating tissue proteolysis of alpha-spectrin by Western blot analysis.
      Correlative organ bath studies were conducted to observe the contractile
      responses of bladder strips to field stimulation and bethanechol administration.
      RESULTS: (1) Sixty minutes of ischemia followed by 30 minutes of reperfusion
      resulted in (a) a reduction in the contractile responses to field stimulation and
      bethanechol (89% and 57%, respectively), and (b) a 72% decrease in native alpha
      spectrin, with a concomitant 300% increase in its breakdown products (BDPs).
      Neither alpha-spectrin nor its BDPs had returned to control levels after 72 hours
      of reperfusion. (2) Twenty-four hours after the creation of a partial
      obstruction, alpha-spectrin BDP levels were increased 330%, then gradually fell
      to 130% of control levels by 14 days after obstruction. Concomitantly, the native
      alpha-spectrin level was decreased 74% 24 hours after obstruction and remained
      low through 7 days after obstruction. At 14 days after obstruction, the alpha
      spectrin levels had recovered to 75% of control levels. CONCLUSIONS: These
      findings suggest that Ca(2+)-dependent proteolysis of the preferred calpain
      substrate alpha-spectrin in urinary bladder tissues is increased significantly by
      both ischemia/reperfusion and partial outlet obstruction. Temporally, proteolysis
      precedes the reduced muscle function resulting from these pathologic conditions.

PMID- 9037303
TI  - Determination of CAG repeat length in the androgen-receptor gene using frozen
      serum.
AB  - OBJECTIVES: To determine CAG repeat length in exon one of the androgen-receptor
      gene, using frozen serum as a source of deoxyribonucleic acid (DNA). METHODS:
      Samples from previously frozen serum samples were prepared for polymerase chain
      reaction (PCR) by heating thawed serum to 100 degrees C and subsequent
      centrifugation at 16,000 g. Three microliters of supernatant were added to the
      PCR in combination with primers flanking the CAG repeat in exon one of the human
      androgen-receptor gene. After 35 cycles, the PCR amplicons were electrophoresed
      on an agarose gel, excised, purified, and sequenced. CAG repeat length was
      directly determined from DNA sequencing gels. RESULTS: Amplified DNA fragments
      were obtained after PCR from 140 of the 200 specimens examined to date. The DNA
      amplicon was successfully sequenced in 111 samples derived from 104 individuals.
      Within this group, the androgen receptor CAG repeat length varied from 11 to 27.
      The median CAG repeat length was 21; the lower and upper quartiles were 18 or
      less and 23 or more, respectively. Results were consistent in each case that CAG
      repeat length was repetitively determined. CONCLUSIONS: The establishment of a
      methodology to determine androgen-receptor gene CAG repeat length from frozen
      serum samples opens multiple new opportunities to explore the potential clinical
      significance of this genetic polymorphism.

PMID- 9037304
TI  - PSA variability versus velocity.

PMID- 9037305
TI  - Reproducibility of pressure-flow variables in patients with symptomatic benign
      prostatic hyperplasia.

PMID- 9037306
TI  - Transperineal prostate needle biopsy guided by transurethral ultrasound in
      patients without a rectum.

PMID- 9037307
TI  - Diagnosis of advanced or noncurable prostate cancer can be practically eliminated
      by prostate-specific antigen.

PMID- 9037308
TI  - The scrotal hitch for hemostasis and edema prevention and scrotal surgery.

PMID- 9037310
TI  - Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and
      invasive duct breast carcinomas.
AB  - Bcl-2 and Bax proteins are coded by a family of genes that take part in the
      manteinance of the balance between cell proliferation rate and programmed cell
      death in multicellular organisms. The Bax gene acts as promoter of cell death by
      opposing the death protector effect of the Bcl-2 gene. Expression of the Bcl-2
      and Bax proteins has been investigated in 58 cases of duct carcinoma in situ
      (DCIS) and duct invasive and invasive lobular carcinomas (IC) of the breast.
      While both proteins were expressed at the same time in normal and benign
      epithelium, different staining patterns were observed according to the degree of
      differentiation of the neoplastic epithelium. In well-differentiated DCIS and
      grade I IC there was a predominance of Bcl-2 protein staining. Grade II lesions
      co-expressed both proteins. Poorly differentiated DCIS displayed a predominantly
      Bax protein staining pattern. Therefore, it appears that Bax protein expression,
      especially in DCIS, relates to more aggressive neoplasms while Bcl-2 protein
      expression is associated with less aggressive malignant lesions.

PMID- 9037311
TI  - E-cadherin (E-cad) expression in duct carcinoma in situ (DCIS) of the breast.
AB  - E-cadherin (E-cad) is an epithelial cell-cell adhesion molecule whose loss or
      reduced expression is associated with a more invasive tumour phenotype. Ninety
      six cases of screen detected pure ductal carcinoma in situ (DCIS) were analysed
      immunocytochemically for expression of E-cad using the HECD-1 mouse monoclonal
      antibody. The in situ component in each case was classified on the basis of
      cytonuclear grade, extent of necrosis, Van Nuys classification and a newly
      devised Cardiff classification. The amount of E-cad expression was assessed semi
      quantitatively using an intensity distribution method. There is significantly
      more expression of E-cad in well-differentiated DCIS when compared with poorly
      differentiated DCIS and this finding is highly significant (P < 0.001)
      irrespective of the classification system used. These findings suggest that
      progressive loss of E-cad expression may occur at an early stage of breast cancer
      development.

PMID- 9037309
TI  - Evaluating radical prostatectomy specimens: therapeutic and prognostic
      importance.
AB  - The pathologic staging of prostate cancer involves determination of the anatomic
      extent and burden of tumor based on the best available data. Proper examination
      of radical prostatectomy specimens is critical in determining cancer stage,
      stratifying patient need for adjuvant treatment, and prediction of patient
      outcome. Differences exist in methods of handling and sampling specimens,
      although publication of practice protocols in recent years has led to convergence
      of opinion. In this report, we evaluate the current aspects of pathologic staging
      of prostate cancer and assessment of prostatectomy specimens. Recent
      international agreement on pathologic staging of prostate cancer should allow
      valid comparisons of surgical treatment from different institutions. The
      vanishing cancer phenomenon is also briefly discussed.

PMID- 9037312
TI  - Induction of apoptosis in a human hepatocellular carcinoma cell line by a
      neutralizing antibody to transforming growth factor-alpha.
AB  - A cell line derived from a Japanese man with hepatocellular carcinoma was
      established in culture and designated OCUH-16. The cell line has the
      morphological and chromosomal features of hepatocellular carcinoma cells and has
      a short doubling time (approximately 33 h). OCUH-16 cells were shown to express
      transforming growth factor-alpha (TGF-alpha) in addition to albumin, DNA
      polymerase-alpha, c-JUN, and the retinoblastoma gene product. Electron microscopy
      revealed TGF-alpha immunoreactivity associated with the cell membrane, but TGF
      alpha was not detected in medium conditioned by OCUH-16 cells by enzyme-linked
      immunosorbent assay. Reverse transcription and polymerase chain reaction analysis
      revealed the presence of TGF-alpha messenger RNA in these cells. Culture of OCUH
      16 cells in the presence of a neutralizing antibody to TGF-alpha inhibited cell
      proliferation and induced many cells to undergo apoptosis (programmed cell
      death). These observations suggest that endogenous TGF-alpha is necessary for
      OCUH-16 cell growth.

PMID- 9037313
TI  - Endocrine cells in hepatobiliary cystadenomas and cystadenocarcinomas.
AB  - We investigated the distribution of endocrine cells in hepatobiliary cystadenoma
      (n = 5, two associated with mesenchymal stroma) and cystadenocarcinoma (n = 3)
      immunohistochemically. In normal livers (n = 20) and livers affected by
      hepatolithiasis (n = 15) used as controls, endocrine cells revealed by
      chromogranin immunostaining were located exclusively in normal or proliferating
      intrahepatic peribiliary glands. In the eight cases of hepatobiliary cystadenoma
      and cystadenocarcinoma, endocrine cells were present in four cases (50%) (1
      cystadenoma, 1 cystadenoma with mesenchymal stroma, and 2 cystadenocarcinomas).
      Endocrine cells tended to be located beneath and among the columnar epithelial
      cells. Intrahepatic peribiliary glands were located in the vicinity of
      cystadenoma or cystadenocarcinoma in six (75%) of the eight cases, and they
      frequently showed cystic dilatation and contained endocrine cells. Intrahepatic
      peribiliary glands were located in the vicinity of the endocrine cells in all
      cystadenomas and cystadenocarcinomas that were positive for endocrine cells.
      These data show that about 50% of hepatobiliary cystadenomas and
      cystadenocarcinomas contain endocrine cells and suggest that hepatobiliary
      cystadenoma and cystadenocarcinoma may originate from intrahepatic peribiliary
      glands.

PMID- 9037314
TI  - Neurogenic potential of Ewing's sarcoma cells.
AB  - We investigated the capacity of eight well-characterized Ewing's sarcoma cell
      lines to differentiate towards a neural phenotype. Ewing's sarcoma cells
      expressed the neuroectoderm-associated antigens such as nerve growth factor (NGF)
      receptor, N-CAM (6H7 and Leu-19) and Leu-7. Ewing's sarcoma cells also exhibited
      the potential for neural differentiation at the mRNA level; neuron-specific
      medium- and low-sized filament (NF-M and NF-L) expression was induced by
      dibutyryladenosine cyclic monophosphate. The pattern of expression of NF-L
      obtained by using alternative polyadenylation sites in Ewing's sarcoma cells
      differed from that in peripheral primitive neuroectodermal tumour (PNET) cells,
      and was similar to that in undifferentiated neural tissues. Furthermore, the NGF
      receptors detected by immunohistochemistry were found to be non-functional as
      assayed by c-fos induction with NGF treatment. The results indicate that Ewing's
      sarcoma cells maintain a primitive phenotype and have the potential to
      differentiate into a neural phenotype, indicating that Ewing's sarcoma is
      distinct from PNET.

PMID- 9037315
TI  - Nonrandom gain of chromosome 7 in central neurocytoma: a chromosomal analysis and
      fluorescence in situ hybridization study.
AB  - Central neurocytoma is a benign, slow-growing neoplasm with favourable prognosis.
      Biomolecular analysis has failed to demonstrate significant alterations, and no
      cytogenetic alterations have been reported. In this study we demonstrate
      chromosome 7 gain in three of nine neurocytomas (33%). Traditional cytogenetic
      analysis performed in four of the nine cases identified trisomy 7 as the sole
      chromosomal abnormality in one case. Interphase cytogenetics utilizing
      fluorescent in situ hybridization (FISH) on cell suspensions from formalin-fixed
      paraffin-embedded tumour tissue performed in all nine cases detected trisomy 7 in
      two more cases and tetrasomy in another. Our results suggest that chromosome 7
      gain is a feature of neuroectodermal tumorigenesis, possibly conferring growth
      advantage on the neoplastic cells. FISH on interphase nuclei is a valuable
      adjunct in the genetic evaluation of rare central nervous system neoplasms with
      low baseline proliferative activity.

PMID- 9037316
TI  - The distribution and co-localization of nitric oxide synthase and vasoactive
      intestinal polypeptide in nerves of the colons with Hirschsprung's disease.
AB  - The distribution and co-localization of nitric oxide synthase (NOS) and
      vasoactive intestinal polypeptide (VIP) were examined by means of
      immunohistochemistry and NADPH diaphorase (NADPH-d) histochemistry in the gut of
      patients with Hirschsprung's disease. In the normoganglionic segment, many
      nitrergic nerve cells were localized in Auerbach's plexus and nerve fibres were
      observed preferentially in the circular muscle. The submucosal nitrergic nerve
      cells were mainly situated in Schabadasch's plexus with occasional cells
      demonstrable in Meissner's plexus. NOS and VIP were co-localized in most ganglion
      cells of Auerbach's plexus. In the oligoganglionic segment, a marked reduction of
      NOS- and VIP- positive nerve cells and fibres was noticed in both the myenteric
      and submucosal plexuses, and nitrergic fibres had disappeared in the inner layer
      of the circular muscle. In the aganglionic segment, NOS and VIP were revealed
      only in extrinsic nerve fasciculi and rami and co-localized in a few fibres. From
      these observations, the inner layer of the circular muscle of the oligoganglionic
      segment and the whole of the muscularis propria of the aganglionic segment were
      considered to be totally lacking in nitrergic innervation. Nitrergic nerves of
      the human colon comprise both intrinsic and extrinsic elements and the majority
      of intrinsic nitrergic nerve cells contain VIP. Very low numbers of extrinsic
      nitrergic fibres contain VIP.

PMID- 9037317
TI  - In vivo responses of macrophages and myofibroblasts in the healing following
      isoproterenol-induced myocardial injury in rats.
AB  - To clarify the relation between macrophage and myofibroblast involvement in
      various myocardial diseases, the authors investigated the kinetics of these cells
      in the healing (scar tissue formation) following isoproterenol-induced myocardial
      injury in rats. Alpha-smooth muscle actin (alpha-SMA) expressing myofibroblasts
      were seen at the border of the affected area and appeared in the greatest numbers
      on days 3-7 post-injection, followed by a gradual decrease by day 35. The peak on
      day 3 was consistent with the timing of the highest proliferative activity of
      myofibroblasts. The number of ED1-positive macrophages began to increase as early
      as day 1, reaching a peak on day 3 within the injured myocardium. The expansion
      of ED1-positive macrophages preceded an increased number of alpha-SMA-positive
      myofibroblasts suggesting that myofibroblast proliferation and activation may be
      mediated by factors released by ED1-positive macrophages in response to
      myocardial injury. The number of ED2-positive tissue-fixed, resident macrophages
      gradually, increased from day 3 post-injection, and peaked on day 14, but the
      number of ED2-positive macrophages was consistently fewer than that of ED1
      positive macrophages during the 35 day-observation period after the injection.
      The labelling index of the ED2-positive cells was maximal on day 14, indicative
      of local proliferation of resident macrophages. In the healing process after
      myocardial injury, ED1-positive macrophages increase markedly in the early
      stages: ED2-positive macrophages appear later.

PMID- 9037318
TI  - Noradrenergic hyperinnervation may inhibit necrosis of coronary arterial smooth
      muscle cells in stroke-prone spontaneously hypertensive rats.
AB  - Noradrenergic (NA) nerve fibre distribution and vascular smooth muscle morphology
      were investigated in the coronary artery of stroke-prone spontaneously
      hypertensive rats (SHRSP). Fluorescent NA nerve fibres of SHRSP aged 10, 30, 60,
      90 and 180 days were examined by the glyoxylic acid method and compared with
      those of age-matched normotensive Wistar Kyoto (WKY) rats. The distribution
      densities of NA nerve fibres were measured by quantitative image analysis using
      the Interactive Bildanalyse System. The densities of NA nerve fibres of the left
      coronary artery of SHRSP were significantly higher than those of WKY rats at all
      ages examined. NA hyperinnervation in the coronary artery of SHRSP may be caused
      by the hyperfunction of the stellate ganglia which innervate the coronary
      arteries. Scanning electron microscopy observations showed that the surface of
      smooth muscle cells of the left coronary artery in SHRSP was smooth and similar
      to that of WKY rats at 120 days of age, but was slightly modified by more
      invaginations and projections than that in WKY rats at 180 days of age. No
      necrotic cells, however, were found in SHRSP. By transmission electron microscopy
      the smooth muscle cells in SHRSP were shown to be irregular in profile with deep
      indentations of the plasma membrane and surrounded by many layers of basal
      laminalike material, but no necrotic cells were found. We suggest that NA
      hyperinnervation protects the vascular smooth muscle cells from necrosis in the
      coronary artery of SHRSP by a trophic effect mediated by NA nerve fibres.

PMID- 9037319
TI  - Gynandroblastoma of the ovary: a case report with an immunohistochemical and
      ultrastructural study.
AB  - An ovarian gynandroblastoma in a 60-year-old woman is described. The cut-surface
      of the right ovary showed multiple macrofollicles separated by white fibrous
      tissues and multiple ill-defined yellowish nodules. The tumour consisted of
      substantial amount of a granulosa cell element and a Sertoli cell element with
      intermingled Leydig cells. Immunohistochemically, the tumour cells in both the
      granulosa cell and Sertoli cell elements were positive for cytokeratin CAM5.2.
      The granulosa cell element showed strong membrane staining of Ewing's sarcoma
      antigen 013 and the Sertoli cell element was locally positive. Vimentin was
      observed in both the Sertoli cell element and the granulosa cells. Both elements
      and the Leydig cells were uniformly negative for epithelial membrane antigen,
      muscle specific actin, CD31 and CD34. The tumour was aneuploid by flow cytometry.
      The patient was well with no evidence of tumour five months after surgery.

PMID- 9037320
TI  - Prostate pathology case study seminar.
AB  - Great strides have been made in the past decade in our understanding of the
      pathology of the prostate. Diagnostic criteria have been proposed, debated, and
      refined for a number of entities, including prostatic intraepithelial neoplasia,
      atypical adenomatous hyperplasia, basal cell proliferations, postatrophic
      hyperplasia, verumontanum mucosal gland hyperplasia, and numerous new variants of
      prostatic adenocarcinoma such as ductal adenocarcinoma, mucinous carcinoma,
      signet ring cell carcinoma, and lymphoepithelioma-like carcinoma. This report
      presents a series of case studies in prostate pathology which illustrate some of
      the contemporary issues which confront the pathologist and urologist.

PMID- 9037321
TI  - The alterations in insulin sensitivity during angiotensin converting enzyme
      inhibitor treatment are related to changes in the calcium/magnesium balance.
AB  - The present analysis was undertaken to investigate the relations between
      alterations in mineral factors, especially the balance between serum calcium and
      magnesium concentrations (S-Ca and S-Mg, respectively), and variables reflecting
      glucose and lipid metabolism during angiotensin converting enzyme (ACE) inhibitor
      treatment. A total of 96 patients with essential hypertension, participating in
      four double-blind studies with four different ACE inhibitors and similar
      protocols, were included. At the end of the initial placebo period and at the end
      of the period of active drug treatment, a hyperinsulinemic euglycemic clamp test
      was carried out, lipoprotein status was assessed, and the concentrations of serum
      electrolytes were measured. The serum ACE activity was determined in the group
      treated with fosinopril. Changes in insulin sensitivity index (M/I) were directly
      correlated to alterations in S-Mg (r = 0.24, P < .02), and inversely correlated
      to changes in S-Ca (r = -0.19, P = .07) and the ratio between serum calcium and
      magnesium concentrations (Ca/Mg) (r = -0.27, P < .008). The change in total serum
      triglycerides (S-Tg) was inversely correlated to the change in S-Mg (r = -0.35, P
      < .0005), and directly correlated to the change in Ca/Mg ratio (r = 0.36, P <
      .0004). The reduction in serum ACE activity correlated to a more pronounced
      increase in S-Mg r = -0.62, P < .002), and decrease in the Ca/Mg ratio (r = 0.73,
      P = .0002). We conclude that the changes in the studied metabolic variables and
      serum ACE activity during ACE inhibitor treatment are related to alterations in
      mineral status and the balance between calcium and magnesium concentrations in
      serum.

PMID- 9037322
TI  - Associations of hypertension and complications in non-insulin-dependent diabetes
      mellitus.
AB  - Hypertension is a common comorbidity with non-insulin-dependent diabetes mellitus
      (NIDDM). Data are somewhat inconsistent as to whether hypertension exacerbates
      diabetic complications in this population. Therefore, we examined the
      relationship between hypertension and vascular complications of NIDDM in the 950
      patients enrolled in the prospective and randomized Appropriate Blood Pressure
      Control in Diabetes (ABCD) study. We found both systolic and diastolic
      hypertension to be associated with diabetic nephropathy (P < .001) as well as
      with its macrovascular complications (P < .05). Our present results also
      demonstrated that there was a significant relationship between hypertension and
      peripheral vascular disease (P < .05), and left ventricular hypertrophy (P <
      .001). There was, however, no apparent relationship between hypertension and
      diabetic neuropathy. Thus, arterial pressure may be a major determinant of
      complications in NIDDM.

PMID- 9037323
TI  - Baroreflex control of muscle sympathetic nerve activity in mild hypertension.
AB  - The importance of the arterial baroreflex control of muscle sympathetic nerve
      activity (MSNA) has been investigated in physiological conditions and in
      cardiovascular dysfunctions. However, there is no consensus about the role played
      by the MSNA in hypertensive states, probably due to the diversity of the methods
      used to study the arterial baroreflex control of MSNA. In the present study we
      evaluated the reflex changes in MSNA by increasing and decreasing the mean
      arterial pressure (MAP) through 1 min intravenous infusion of phenylephrine (1
      microgram/kg) and sodium nitroprusside (1 microgram/kg), respectively, in eight
      normotensive and eight mild hypertensive subjects. Both MAP and MSNA were
      significantly higher in hypertensive (117 +/- 2 mm Hg and 30 +/- 3 bursts/min)
      than in normotensive (96 +/- 4 mm Hg and 20 +/- 3 bursts/min) subjects. The
      reflex gain was calculated by the ratio percent of changes in MSNA/percent
      changes in MAP. The maximal reflex gain was statistically similar in normotensive
      and hypertensive groups during phenylephrine (5.1 +/- .4 v 4.3 +/- 0.4 bursts/mm
      Hg, respectively) and nitroprusside (10.7 +/- 2.3 v 8.1 +/- 1.3 bursts/mm Hg,
      respectively) infusion. The present data showing that arterial baroreflex control
      of MSNA is not depressed in hypertensive subjects indicate that the elevated
      basal MSNA and the mild hypertension in human beings is not a consequence of
      baroreflex control of MSNA dysfunction.

PMID- 9037324
TI  - 24 h blood pressure profile affects the left ventricle independently of the
      pressure level. A study in untreated essential hypertension diagnosed by office
      blood pressure readings.
AB  - This work examines whether the 24 h blood pressure (BP) pattern per se might
      affect the left ventricular structure independently of the pressure level. One
      hundred subjects with abnormally high office BP readings who had never received
      any antihypertensive treatment were submitted to 24 h ambulatory BP monitoring
      and left ventricular echocardiographic assessment. They were classified into two
      groups, as follows: dippers (group 1), consisting of 46 subjects whose mean
      nighttime systolic BP was reduced by at least 10% in comparison to the
      corresponding daytime value, and nondippers (group 2), consisting of 54 subjects
      whose nighttime BP did not drop or was reduced by < 10%. Left ventricular mass
      and end-diastolic volume values, both normalized for body surface area, were
      significantly higher in nondippers (r = 3.12, P < .003, and r = 7.46, P < .001,
      respectively). The two groups did not differ in diastolic thickness of either
      intraventricular septum or left ventricular posterior wall (both values
      normalized for body surface area), in mean 24 h systolic or diastolic or average
      blood pressure, or in age. In conclusion, in untreated essential hypertension
      diagnosed on the basis of abnormal office BP readings, the higher incidence of
      left ventricular mass increase in subjects unable to reduce their blood pressure
      during the night was more due to left ventricular dilatation than to myocardial
      wall thickening. The effect of the 24 h BP profile on left ventricular volume
      appears to be independent of both the BP level and age.

PMID- 9037325
TI  - Factors confounding assessment of ambulatory blood pressure monitors, studied
      during formal evaluation of the Tycos Quiet-Trak.
AB  - The credibility of studies assessing ambulatory blood pressure monitoring (ABPM)
      devices will be enhanced by minimizing opportunities to manipulate the outcome
      through biased selection of patient volunteers, and by insuring that participants
      are representative of the target patient population. While subjecting the Welch
      Allyn Quiet-Trak to the British Hypertension Society (BHS) protocol, we examined
      the extent to which certain candidate characteristics might influence device
      assessment. The Quiet-Trak achieved an A grade overall. During its field testing,
      daytime physical activity measured with a wrist-mounted, piezoelectric
      accelerometer, influenced significantly the rate of measurement rejection. The
      tertiles of subjects with highest and lowest levels of daytime physical activity
      (64 +/- 16 and 35 +/- 10 activity units; P < .001) exhibited significantly
      different measurement rejection rates (10 +/- 3 and 3 +/- 2 daytime rejects; P <
      .001)). Most rejected readings occurred during episodes of high physical
      activity. During static evaluation (Phase V), the level of systolic BP influenced
      the accuracy of diastolic BP estimation; above 190 mm Hg systolic BP, estimates
      of diastolic BP differed significantly from manual measurements. Subjects' age
      and arm circumference influenced neither field nor static evaluation.
      Retrospective comparison of the study subjects with 120 consecutive ABPM clinic
      attenders revealed (1) that participants in field testing were younger, had lower
      BP but were equally active compared with clinic patients; and (2) that Phase V
      participants exhibited higher systolic (155 +/- 42 v 135 +/- 15 mm Hg; P < .001)
      but similar diastolic BP levels compared to controls. The reliability of ABPM
      validation protocols would be enhanced by: (a) incorporation of objective
      measurement of physical activity during field testing, demonstrating normal
      levels of activity; (b) requiring that field testing be conducted in
      representative patients rather than normal volunteers; and (c) a greater focus in
      both static and field testing on those levels of blood pressure that are relevant
      in clinical practice.

PMID- 9037326
TI  - Coronary vascular reserve is similarly reduced in hypertensive patients without
      any other coronary risk factors and in normotensive smokers and
      hypercholesterolemic patients with angiographically normal coronary arteries.
AB  - Hypertensive patients (HTP) with left ventricular hypertrophy have reduced
      coronary vascular reserve (CVR), but in HTP without left ventricular hypertrophy,
      CVR is within the normal range according to values determined in subjects without
      taking into account coronary risk factors such as cigarette smoking or
      hypercholesterolemia. To examine the influence of hypertension, cigarette
      smoking, and hypercholesterolemia on coronary flow and resistance reserve,
      coronary flow velocity was measured using a Doppler catheter before and after a
      maximally vasodilating dose of papaverine in 15 normotensive subjects without any
      coronary risk factors (Group 1), in 12 nonsmoker HTP with normal lipid profiles
      who had never been treated (Group 2), in 8 normotensive smoker patients (Group
      3), in 9 normotensive nonsmoker patients with hypercholesterolemia (Group 4), and
      in 13 normotensive smoker patients with hypercholesterolemia (Group 5). All
      patients had normal coronary arteriography and left ventricular mass and
      function. Peak-to-resting coronary flow velocity ratio and mean aortic pressure
      were used to determine coronary flow reserve (CFR) and a minimal coronary
      vascular resistance index (MCVRI). Results show that in groups 2, 3, 4, and 5
      comparatively to Group 1, CFR was similarly reduced (4.60 +/- 0.74 [P < .001],
      4.59 +/- 0.35 [P < .001], 5.01 +/- 0.55 [P < .05], 5.03 +/- 0.78 [P < .05],
      groups 2 to 5, respectively, compared to group 1 5.66 +/- 0.68), and that MCVRI
      was similarly augmented (0.19 +/- 0.03 [P < .01], 0.20 +/- 0.0 [P < .001], 0.19
      +/- 0.02 [P < .05], 0.19 +/- 0.03 [P < .05], groups 2 to 5, respectively,
      compared to group 1 0.16 +/- 0.02). In conclusion, HTP without left ventricular
      hypertrophy have a similar reduction of their CVR as smokers and
      hypercholesterolemic patients when compared to a group of subjects without any
      coronary risk factors. This should be taken into account when determining a group
      of control subjects for coronary reserve.

PMID- 9037327
TI  - The antihypertensive efficacy of the novel calcium antagonist mibefradil in
      comparison with nifedipine GITS in moderate to severe hypertensives with
      ambulatory hypertension.
AB  - Mibefradil is a novel calcium antagonist that blocks selectively the T-type
      calcium channels. In this double-blind forced titration study design we compared
      the effects of mibefradil 50, 100, and 150 mg and nifedipine GITS 30, 60, and 90
      mg monotherapies or combined with lisinopril 20 mg in 71 moderate to severe
      hypertensives (59 men and 12 women) with confirmed ambulatory hypertension. An
      incremental dose-response effect was observed both in clinic and ambulatory blood
      pressure parameters during treatment with mibefradil and nifedipine GITS alone
      and combined with lisinopril. At maximal dosage, patients treated with mibefradil
      experienced a greater (P < .05) reduction in clinic and ambulatory diastolic
      blood pressures as well as a greater response rate (86% v 69%). Trough:peak
      ratios for systolic and diastolic blood pressures were > 90% at each dose level.
      Significant decrease in baseline heart rate was observed with mibefradil 150 mg
      alone or combined with lisinopril, but no patients experienced clinically
      significant atrioventricular conduction abnormalities. Adverse events related to
      vasodilation were more prevalent in the nifedipine GITS group. Consequently, the
      results of the present study demonstrate that the novel calcium channel blocker
      mibefradil, either alone or in combination with lisinopril, is effective in
      reducing clinic and 24-h blood pressures while decreasing heart rate and is well
      tolerated in patients with moderate to severe hypertension.

PMID- 9037328
TI  - Lack of association of the angiotensin converting enzyme polymorphism with
      essential hypertension in a Chinese population.
AB  - To examine the association between insertion/deletion (I/D) polymorphism of the
      angiotensin converting enzyme (ACE) gene and essential hypertension in a Chinese
      population, a case-control study was conducted using 157 hypertensive and 115
      normotensive subjects. The I/D polymorphism of the ACE gene was identified by
      polymerase chain reaction. Plasma ACE activity was determined using
      spectrophotometry. The difference of allele frequencies between normotensives and
      hypertensives was statistically significant (chi 2 = 4.467, P = .035), while the
      genotype distribution was not different between normotensive and hypertensive
      subjects (chi 2 = 3.954, P = .138). Plasma ACE activity was highest in the DD
      genotype, followed by the ID genotype, and the lowest in the II genotype (P =
      .0001 in normotensives and P = .163 in hypertensives, respectively). Thus, we
      conclude that the ACE gene polymorphism is not associated with essential
      hypertension in this Chinese population, but plasma ACE activity is genetically
      determined in the normotensive Chinese.

PMID- 9037329
TI  - Effects of cicaprost and fosinopril on the progression of rat diabetic
      nephropathy.
AB  - We have studied the effects of chronic therapy with cicaprost (a PGI2 analog),
      fosinopril (a converting enzyme inhibitor), and the combination of both drugs on
      the progression of experimental diabetic nephropathy. Uninephrectomized
      streptozotocin-induced diabetic rats were maintained for 8 months with plasma
      glucose between 13.7 and 22.0 mmol/L to hasten renal damage. Systemic and renal
      parameters were measured periodically, and at sacrifice structural and
      morphometrical renal studies were performed to evaluate diabetic injury. Control
      rats exhibited characteristic features of this model, such as high blood pressure
      and plasma creatinine and urinary albumin excretion, together with prominent
      alterations in the kidney (renal and glomerular hypertrophies, mesangial matrix
      expansion, and tubular alterations). The three therapies attenuated equivalently
      the progression of diabetic renal injury, as estimated by lower urinary albumin
      excretion, renal and glomerular hypertrophies, and a better renal architectural
      preservation. No synergistic action was appreciated with the combined therapy.
      However, renal preservation achieved with cicaprost was not linked to reductions
      in systemic blood pressure, whereas in the groups treated with fosinopril the
      hypotensive effect of this drug could have contributed to the positive outcome of
      the therapy. Therefore, nephroprotection exerted by this PGI2 analog in this
      model seems more related to the derangement of renal local mechanisms than to
      systemic blood pressure control. Finally, the possibility that an impaired
      prostacyclin synthesis or bioavailability is involved in the pathogenesis of the
      diabetic nephropathy in this model underlies our results.

PMID- 9037330
TI  - Evaluation of the IITC tail cuff blood pressure recorder in the rat against
      intraarterial pressure according to criteria for human devices.
AB  - National standards govern the manufacture and marketing of medical devices in the
      United States, including those for indirect blood pressure measurement in man.
      There are no comparable standards for devices for recording in laboratory
      animals. Noninvasive tail cuff blood pressure (BP) recording in the rat is widely
      accepted, but beset by methodologic difficulties. Intraarterial recording is
      regarded as the "gold standard" but is invasive and also susceptible to
      methodologic error. We compared the IITC Mark 12 photoelectric/oscillometric tail
      cuff system (IITC Life Sciences, Woodland Hills, CA) versus simultaneous femoral
      intraarterial recordings in spontaneously hypertensive rats, during anesthesia
      and 1 to 2 days after recover (150 recordings under each condition), according to
      the guidelines for human data collection and analysis suggested the American
      National Standard for automated sphygmomanometers. Within- and between-observer
      disagreements in estimates made by two observers from 40 anesthetized recordings
      were less for intraarterial measurements than for the tail cuff method. Within
      observer differences (mean +/- SD of differences [SDD]) for systolic, diastolic,
      and mean pressure were 0 +/- 1, 0 +/- 1, and 0 +/- 1 mm Hg for intraarterial
      versus -1 +/- 3, 0 +/- 8, and 0 +/- 5 mm Hg for tail cuff. Between-observer
      differences were 0 +/- 2, 0 +/- 1, and 6 +/- 2 mm Hg versus 5 +/- 4, 13 +/- 7,
      and 0 +/- 5 mm Hg, respectively. Differences between tail cuff and intraarterial
      methods were 16 +/- 13, -5 +/- 11, and 2 +/- 8 mm Hg in anesthetized animals and
      8 +/- 14, -5 +/- 9, and 0 +/- 9 mm Hg in conscious animals (39% to 82% of
      differences exceeded 5 mm Hg). The upper limits of clinically acceptable
      disagreement in the American National Standard are: mean of 5 mm Hg, SDD of 8 mm
      Hg. The disagreement between tail cuff and intraarterial recordings cannot be
      ascribed to either method with certainty. These findings do not support the
      manufacturer's guarantee of tail-cuff readings within "5 mm Hg of intraarterial."
      Inaccuracy and unreliability of devices intended for laboratory animal use have
      considerable scientific, fiscal, and ethical implications. Marketing of these
      devices should also be governed by rigorous standards.

PMID- 9037331
TI  - The great Hanshin-Awaji earthquake aggravates blood pressure control in treated
      hypertensive patients.
AB  - A major earthquake (Hanshin-Awaji earthquake) struck Kobe on January 17, 1995. We
      had a unique opportunity to study the effect of tremendous psychological stress
      on blood pressure control in 221 hypertensive patients receiving antihypertensive
      medication. During the 4 weeks after earthquake, on average, the mean blood
      pressure increased significantly for both 105 patients who were exposed (living
      in the area of the very severe earthquake) and 116 patients who were not exposed
      (living in the surrounding area) (+4.2 +/- 1.0 mm Hg, P < .001, and +/- 2.4 +/-
      0.7 mm Hg, P < .005, respectively). In the exposed group, the increase in mean
      blood pressure peaked in the first week (+6.7 +/- 1.6 mm Hg, P < .001), declined
      thereafter, and returned to the baseline within 6 weeks after the disaster. The
      earthquake related blood pressure elevation was, however, significantly
      attenuated (P < .02) in patients receiving beta-blockers compared with those
      receiving other drugs. The results indicate that acute psychological stress
      associated with a sudden natural disaster causes blood pressure elevation in
      treated hypertensive patients, and suggest the beneficial effect of beta-blockers
      on such a stress-associated high blood pressure.

PMID- 9037332
TI  - Effect of the Hanshin-Awaji earthquake on home blood pressure in patients with
      essential hypertension.
AB  - At 5:46 AM on January 17, 1995, the Hanshin-Awaji district of Japan was struck by
      a major earthquake. We investigated changes in home blood pressure (BP) of 36
      hypertensive patients before and after the earthquake. In the 16 patients who
      lived within 50 km from the epicenter, the home Bp on the day of the earthquake
      was significantly higher than that just before the earthquake (+11/+6 mm Hg; P <
      .01 for systolic BP and P < .05 for diastolic BP). It remained higher throughout
      the first week after the earthquake, then gradually returned to the baseline
      level within 4 weeks. The home BP did not change significantly in the 20 patients
      who lived farther than 50 km from the epicenter. The earthquake-induced stress
      increased the BP in these hypertensive patients; however, its pressor effect was
      not persistent.

PMID- 9037333
TI  - Role of nitric oxide in modulating the chronic renal and arterial pressure
      responses to angiotensin II.
AB  - The purpose of this study was to determine long-term role of nitric oxide in
      modulating the chronic renal and arterial pressure responses to angiotensin II
      (AII). In normal dogs, intrarenal AII infusion (1.0 ng/KG/min) decreased renal
      plasma flow (RPF) by 31% and glomerular filtration rate (GFR) by 17% and
      increased mean arterial pressure (MAP) by 22%. In dogs with chronic intrarenal NO
      synthesis blockade with N(omega)-nitro-L-arginine methyl ester (3
      micrograms/kg/min), AII decreased RPF by 25% and GFR by 19%, and increased MAP by
      7%. These data indicate that chronic inhibition of NO synthesis within the kidney
      attenuated the long-term renal and arterial pressure responses by AII in dogs.

PMID- 9037334
TI  - Obese hypertensive rabbits develop concentric and eccentric hypertrophy and
      diastolic filling abnormalities.
AB  - We have developed a new small animal model of obesity in which rabbits fed a high
      diet develop abnormalities in common with obese humans, including left
      ventricular (LV) hypertrophy. Using M-mode and two dimensional Doppler
      echocardiography we examined the characteristics of LV hypertrophy and diastolic
      function in obese and lean rabbits. Obese rabbits had greater interventricular
      septum and LV posterior wall thickness and greater LV internal end-diastolic and
      end-systolic diameters. Functionally, obese rabbits had higher A/E ratios.
      Similarly to obese humans, obese hypertensive rabbits developed combined
      concentric and eccentric LV hypertrophy and diastolic filling abnormalities.
      Therefore, this model may be valuable in the study of the development and
      pathology of obesity-related LV hypertrophy.

PMID- 9037335
TI  - Assessing outcomes in population health: moving the field forward.

PMID- 9037336
TI  - Quantitative policy analysis and public health policy: a macro and micro view.
AB  - This article considers three examples of the use of quantitative policy analysis
      in setting public health policy: (1) benefit:cost and cost-effectiveness studies
      of influenza immunization and their role in achieving Medicare reimbursement for
      influenza immunization; (2) the 1993 World Bank World Development Report, which
      compared the burden of various health problems in different regions of the world
      and the cost-effectiveness of interventions for these problems, recommending a
      core set of public health and primary care services as being the most cost
      effective; and (3) the role of the Agency for Health Care Policy and Research and
      how it might change if health care reform legislation such as President Clinton's
      original proposal were to be enacted. Finally, I describe the use of quantitative
      policy analysis to guide policy in one government agency--the Centers for Disease
      control and Prevention (CDC).

PMID- 9037337
TI  - Prevention, policy, and paradox: what is the value of future health?
AB  - Cost-effectiveness is an integral part of health care policy, influencing both
      medical and administrative decisions. However, current research methodology for
      evaluating cost-effectiveness produces several paradoxes, perhaps because it
      incorrectly represents the general populations's view of future health states.
      Recent work introduces clinical and demographic factors to the traditional cost
      benefit model for discounting health outcomes. It suggests a revised model that
      provides a more accurate basis for health policy decision-making. This revised
      model will likely improve the apparent cost-effectiveness of prevention programs,
      which are at a distinct disadvantage in present models. This article presents
      examples of current paradoxes resulting from the standard discounting
      methodology, findings on the variability of health outcomes discount rates in
      patients, and preliminary thoughts on developing a revised model for discounting
      future health outcomes. This revised model should present the value of health
      promotion programs more accurately.

PMID- 9037339
TI  - Screening behaviors and long-term compliance with mammography guidelines in a
      breast cancer screening program.
AB  - INTRODUCTION: Screening for breast cancer is generally underused. In an effort to
      remove common barriers to screening, a free breast cancer screening and education
      program was created for the employees of a large hospital, incorporating
      mammography, clinical breast examination (CBE), and breast self-examination
      (BSE). METHODS: The present study was conducted to evaluate the screening
      behaviors and long-term compliance of asymptomatic women over age 50 who
      participated in the program. Data were obtained from questionnaires administered
      at the time of enrollment (time 1) and annual reenrollment, as well as from
      radiology records. (Time 2 represents the most recent data.) Long-term compliance
      with mammography guidelines was measured by calculating a compliance quotient
      (CQ) for each participant. RESULTS: From time 1 to time 2, subjects significantly
      increased their use of mammography, CBE, and BSE. At time 2, 89.5% of women had
      ever received a mammogram, 42.7% had gotten one in the last year, nearly all
      women (94.6%) had received at least one CBE, 58.0% reported annual CBE, and 44.6%
      of women practiced monthly BSE. CQ was higher among women who remained in the
      program longer, were still active in the program at the time of the study, and
      used screening prior to enrollment. It was also higher in Caucasians and women
      with a family history of breast cancer. CONCLUSIONS: These results show that a
      worksite program that eliminates common barriers to screening can significantly
      increase use of early detection practices. It also demonstrates one method of
      quantifying long-term compliance with mammography guidelines.

PMID- 9037338
TI  - Using cost-effectiveness/cost-benefit analysis to allocate health resources: a
      level playing field for prevention?
AB  - INTRODUCTION: Prevention is being promoted as a means to improve health status
      and to save health care costs. Economic evaluations of prevention (i.e., cost
      effectiveness and cost-benefit analyses) indicate that some prevention
      activities, like many treatments, do not save money, although many are relatively
      cost-effective. It has been suggested, however, that prevention is held to a
      higher standard than treatment because prevention programs are expected to
      demonstrate cost savings, and that the methods of economic evaluation understate
      the cost-effectiveness of prevention. Although the converse assertion is less
      commonly made, economic evaluations may also overstate the cost-effectiveness of
      prevention. The purpose of this article is to examine how the methods of economic
      evaluation may systematically understate, or overstate, the cost-effectiveness
      (or net benefits) of prevention. METHODS: We examine three key methods: (1) how
      future costs and benefits are valued ("discounting"), (2) how costs and benefits
      to people beyond those who are the users of prevention are valued
      ("externalities"), and (3) how nonmonetary costs and benefits to individuals are
      valued ("intangibles"). RESULTS: We discuss several recommendations for each key
      method, and we use a hypothetical example of the cost-effectiveness of a vaccine
      to prevent human immunodeficiency virus (HIV) to illustrate our points.
      CONCLUSIONS: We conclude that the methods of economic evaluation may both
      understate and overstate the cost-effectiveness of prevention.

PMID- 9037340
TI  - The University of Virginia health promotion and disease prevention program.
AB  - INTRODUCTION: Proof of effectiveness now exists for many health promotion and
      disease prevention practices, yet the importance of this knowledge is not widely
      appreciated, and a large percentage of the population does not receive this care.
      Universities with comprehensive academic medical centers are particularly
      appropriate places for providing health promotion programs. The University of
      Virginia began a health promotion and disease prevention program for employees in
      1990. METHODS: Periodic health risk appraisal, with follow-up and selected
      interventions, is offered to approximately 14,000 employees as a cost-free fringe
      benefit. Health risks are assessed with a modification of the Carter Center
      Health Risk Appraisal. Results are given to participants in group sessions;
      referrals are made for clinical preventive services and interventions, as needed.
      RESULTS: During the first three years, 29% of the employee population
      participated in the program. Participants were more likely to be young, female
      and not African American. Nearly 96% had one or more risk factors, with an
      average of 3.6 risk factors overall. Participants on average had 1.8 risk factors
      for cardiovascular disease; 0.3 for cancer; 0.6 for injury; 0.1 for alcohol
      abuse; and 0.7 for mental health. Nonparticipants were not receiving similar
      comprehensive health risk appraisal elsewhere. CONCLUSIONS: University of
      Virginia employees have multiple health risks, not detected through their usual
      health care, for which effective interventions are available. This population
      probably reflects conditions throughout the state and nation. Academic medical
      centers should place high priority on establishing health promotion programs as
      part of their responsibilities to society.

PMID- 9037341
TI  - Awareness of consensus preventive medicine practice guidelines among primary care
      physicians.
AB  - INTRODUCTION: Since documented low use of preventive medicine practices may be
      due to lack of acquaintance with recommended practices, we measured the level of
      awareness of specific consensus recommendations and assessed factors that might
      influence awareness. METHODS: We surveyed 326 randomly selected Kansas primary
      care physicians stratified by urban-rural location and medical specialty (family
      practice, internal medicine, obstetrics-gynecology, and pediatrics) using a
      structured computer-assisted interview or questionnaire composed of 11 specialty
      specific multiple choice knowledge questions based on selected published
      consensus recommendations. RESULTS: With a 90% response rate to our survey, chi 2
      testing and analysis of variance (ANOVA) showed (1) correct response rates
      ranging from 27% (hypertension treatment threshold) to 99% (follow-up
      mammography) with a correct response rate of at least 70% for seven of the 11
      questions; (2) no consistent differences for overall correct response rates among
      medical specialties and between practice location, gender, years in practice,
      preventive medicine exposure during residency or through continuing medical
      education courses, or acquaintance with source publications; and (3) higher
      correct response rates for six of 11 questions among physicians with board
      certification. CONCLUSIONS: Our results suggest that low use of prevention
      practices by physicians is likely due to factors other than lack of physician
      knowledge of published consensus recommendations.

PMID- 9037342
TI  - Effect of a cancer screening intervention conducted by lay health workers among
      inner-city women.
AB  - INTRODUCTION: We conducted a randomized controlled trial to determine if an in
      home educational intervention conducted by lay health workers (LHWs) could
      increase adherence among low-income, inner-city, African-American women to breast
      and cervical cancer screening schedules. METHODS: We recruited 321 African
      American women from diverse inner-city sources. After baseline interviews, they
      were randomly assigned to either the intervention (n = 163) or the control (n =
      158) group. Those in the intervention group were visited in their homes up to
      three times by LHWs who provided a culturally sensitive educational program that
      emphasized the need for screening. RESULTS: Ninety-three (93) women in the
      intervention group and 102 in the control group completed the postintervention
      interview. For Pap smears, the increase in screening was similar in both groups.
      For clinical breast exams (CBEs), however, there was a modest increase in the
      intervention group. The improvement was greatest for mammography, for which there
      was a 10% to 12% increase. Among women who were not on recommended schedules at
      baseline, the improvement was substantial and greater in the intervention group.
      CONCLUSIONS: LHWs' intervention appeared to improve the rate at which inner-city
      women obtained CBEs and mammograms, but had no effect on Pap smears. A high
      attrition rate weakened our ability to make conclusive statements about the exact
      impact of the intervention.

PMID- 9037343
TI  - Representations of menopause and their health care implications: a qualitative
      study.
AB  - INTRODUCTION: Menopause is primarily represented as a medical condition with its
      associated body changes described as symptoms in need of treatment. The purpose
      of this study was to determine whether women's representations of and responses
      to menopause reflected this medical perspective. It is based on a secondary
      analysis of data from an earlier study in which the menopause experience of 17
      middle-aged women was examined. METHODS: The original study used a qualitative
      methodology in which data were collected by means of semistructured interviews
      and then analyzed for primary categories of meaning. Interview transcripts were
      reanalyzed for the current study. RESULTS: Findings of the analysis indicate
      that, although the women were relatively uninformed about menopause, they
      identified themselves as menopausal on the basis of both positively and
      negatively defined physical and psychological changes that they associated with
      it. These changes were also associated with aging in general. Furthermore,
      although the women responded to menopause as a time-limited physiological event
      that sometimes required medical attention, they perceived it primarily as a
      marker or symbol of more general life-stage developmental issues and responded
      with both lifestyle changes and a search for new meaning. DISCUSSION: These
      findings indicate that the women's perception of and response to menopause
      reflected both medical and nonmedical representations. Health care implications
      include the importance of health care providers supporting menopausal women in
      their search for both information and meaning, and of researchers investigating
      both medical and nonmedical approaches to reducing the negative health-related
      effects of decreased estrogen levels in menopausal women.

PMID- 9037344
TI  - Psychosocial factors and health status in women with rheumatoid arthritis:
      predictive models.
AB  - INTRODUCTION: Health status, and consequently productivity and quality of life,
      depends on a multitude of factors. Numerous psychosocial factors have been
      associated with the concurrent health status of individuals with chronic disease.
      Previous studies have examined the relationship between singular psychosocial
      factors and health status in rheumatoid arthritis. This study evaluated the
      simultaneous interrelationships among selected psychosocial variable and health
      outcomes using data from a study of younger women diagnosed with rheumatoid
      arthritis (RA). METHODS: The hypothesized models were examined using data from a
      survey of 185 women with a mean age of 43 years, diagnosed with RA for an average
      of 6.6 years. Participants in the study completed the following measures: (1)
      Arthritis Impact Measurement Scales, (2) Multidimensional Pain Inventory, (3)
      Daily Hassles Scale, (4) Interpersonal Support Evaluation List, and (5) Perceived
      Self-Efficacy Scale. RESULTS: Using path analysis, the information provided by
      the LISREL program, and extant theory, two models were tested. The data provided
      support for all but two of the hypothesized relationships in the model predicting
      physical functioning. Pain severity and self-efficacy emerged as important
      variables in understanding individual variations in perceived physical
      functioning. In the second model, using perceived well-being as the outcome, two
      bidirectional relationships were noted: one between affective distress and social
      support, and the second between perceived well-being and daily stress.
      CONCLUSIONS: The models evaluated in this study support the provision of
      multifaceted interventions aimed at enhancing a woman's ability to manage her
      pain and stress while also enhancing her beliefs in her own abilities.

PMID- 9037345
TI  - Multiple familial lipomatosis with polyneuropathy, an inherited dominant
      condition.
AB  - A 22-year-old man had polyneuropathy, facial dysmorphia, atopia and multiple
      lipomatosis. His mother had neuropathy but not lipomatosis as two of her first
      cousins. The proband's grandmother had multiple lipomatosis as her own mother and
      a sister of her mother, but they didn't have neuropathy. This family is an
      example of a dominant syndrome the principle features of which are
      polyneuropathy. Variable expression could account for the phenotypic differences,
      combined with multiple lipomatosis.

PMID- 9037346
TI  - Another patient with a deletion 14q11.2q13.
AB  - We report another case of a de novo interstitial del (14) (q11.2q13). The
      patient's karyotype was 46,XY,del(14) (q11.2q13) [62]/46,XY [1]. In situ
      hybridization excluded any additional abnormalities such as a translocation or
      insertion. The phenotype of our patient is compared with those previously
      published. Comparison of the chromosome 14 short arm polymorphisms of the patient
      and his parents indicated that the paternal chromosome 14 was deleted.

PMID- 9037347
TI  - Familial deletion of chromosome 18 (p11.2).
AB  - Familial transmission of del (18p) syndrome from a mother to her daughter is rare
      and has been reported only once before. We report a female patient referred to us
      at age 18 years because of mental retardation associated with short stature.
      Similar clinical features are also seen in her mother. Chromosome analysis
      revealed a 46,XX, del (18) (p11.2) karyotype in both the proposita and her
      mother. Fluorescence in situ hybridization with whole chromosome paint for
      chromosome 18 showed no evidence of translocation. Because of the familial
      transmission of del (18p), this case has wider implications in genetic
      counseling.

PMID- 9037348
TI  - Centromeric alphoid sequences are breakage prone resulting in pericentromeric
      inversion heteromorphism of qh region of chromosome 1.
AB  - Structural variations in the pericentromeric region of chromosome 1 are
      considered the norm. We characterized a chromosome 1 with an inversion by FISH
      technique and suggested that the origin of pericentromeric heteromorphism is far
      more complex than previously suggested. It is postulated that similar to the
      centromeric alphoid DNA sequences of chromosome 9, chromosome 1 also possesses a
      "breakage prone" centromeric domain which may be a possible cause of such
      inversions involving the secondary constriction region.

PMID- 9037349
TI  - Molecular genetics of hereditary elliptocytosis and hereditary spherocytosis.
AB  - Red cells ow their mechanical properties, that is, their resistance and their
      elastic deformability, to a protein network that laminates the lipid bilayer and
      to proteins spanning the latter. All proteins are interconnected. Their
      structure, as well as the structure of the corresponding genes, will be outlined.
      Numerous mutations have allowed to reclassify hereditary elliptocytosis (HE) and
      poikilocytosis (HP), and, more recently, hereditary spherocytosis (HS) into well
      defined subsets of hereditary hemolytic anemias. HE stems from changes in the
      SPTA1, SPTB, EL1 and (exceptionally) GPYC genes that encode spectrin alpha- and
      beta- chains, protein 4.1 and glycophorin C/D, respectively. HS derives from
      altercations in the ANK1, EPB3 and ELB42 genes, encoding ankyrin, band 3 and
      protein 4.2, respectively, and also in the SPTA1 and SPTB genes. We will present
      a repertory of the known mutations. Innumerable polymorphisms will not be
      considered here, except for a few remarkable ones. Some general points must be
      stressed on. (a) Clinically conspicuous disorders are often the result of two
      alleles interacting in trans to one another. Whereas one allele causes moderate
      symptoms by itself, the other one is usually silent in the simple heterozygous
      (and exceptionally in the homozygous) state. As a result, the number of
      potentially pathogenic alleles is much more important than had been initially
      suspected. (b) The reduction or the loss of a protein within multiprotein
      assemblies are frequently encountered in red cell membrane genetic diseases; it
      leads to the disruption of the complexes with the possible disappearance of the
      other proteins than the mutated protein. (c) The above genes being also expressed
      in nonerythroid tissues, one starts finding multisyndromic conditions adding non
      hematological manifestations to hemolysis. It is puzzling, though, that such
      situations are not more frequent. (d) In practice, the molecular diagnosis of HE
      and HS has reached a semi-routine stage that helps very much the paediatricians
      and haematologists.

PMID- 9037350
TI  - Localization of TEC to 9q22.3-q31 by fluorescence in situ hybridization.
AB  - The TEC gene encodes for a novel orphan nuclear receptor. Recently, it has been
      shown to be involved in the recurrent t(9;22) translocation observed in
      extraskeletal myxoid chondrosarcoma, in a fusion gene with the EWS gene. We
      report her on its precise localization on chromosome 9 by fluorescence in situ
      hybridization.

PMID- 9037351
TI  - Alphoidless centromere of a familial unstable inverted Y chromosome.
AB  - We report on a 3-generation pedigree in which an inverted unstable Y chromosome
      had no phenotypical or reproductive repercussion despite a sizable proportion of
      secondary aneuploidies (mainly 45, X cells) in lymphocytes. This chromosome was
      metacentric and had a single Cd-positive primary constriction, but occasionally
      assumed a normal acrocentric aspect. FISH using the probe DYZ3 revealed a single
      strong signal; unexpectedly, the signal was outside the primary constriction and
      appeared to map in the middle of p, that is, at the usual centromeric
      localisation. Therefore, this chromosome should be regarded as a remarkable
      pseudodicentric because the major alphoid array was located at the inactive
      centromere but not at the active one. This chromosome may have resulted from a) a
      transcentric inversion with the 48 bp satellite array of proximal Yq being
      relocated next to the Yq heterochromatin, or b) an intrachromosomal insertion of
      nonalphoid centromeric sequences.

PMID- 9037352
TI  - Down syndrome with unusual chromosome translocation: case report and review.
AB  - We report a case of Down syndrome with unusual chromosome translocation. The
      proband is a 1 year old male with 47, XY, der (5) t(5;21) (q11:q21), + der (5)
      t(5;21). The mother's karyotype was 46 XX, der (5) t(5,21) (q11:q21). The
      chromosome imbalance resulted from 3:1 meiotic segregation.

PMID- 9037353
TI  - Incidence of breakpoints in pericentric inversions of chromosome 4.
AB  - We report a new pericentric inversion of chromosome 4 in a female who has had two
      consecutive fetal losses during the first trimester conception. Cytogenetic
      findings with GTG-banding revealed a 46,XX,inv(4) (p13q13) karyotype in her
      peripheral blood cells. The breakpoint on the long arm is different from any
      other previously described case. A comprehensive bibliography of reported cases
      with pericentric inversion is also tabulated.

PMID- 9037354
TI  - Carboplatin in the combination chemotherapy of non-seminomatous germ cell
      tumours.

PMID- 9037355
TI  - Towards new prognostic factors in diffuse large cell non-Hodgkin's lymphoma.

PMID- 9037356
TI  - High-dose chemotherapy in germ-cell tumors.
AB  - The majority of patients with advanced-stage germ-cell tumor are curable by
      cisplatin-based chemotherapy, but about 10% of those in the good-risk and 30%-50%
      in the poor-risk groups will experience relapse. Patients in first relapse have a
      60% chance of entering a second complete remission and a 15%-25% probability that
      it will be durable. Regimens of high-dose chemotherapy with hematopoietic stem
      cell support have been developed specifically for this patient population; they
      are usually based on combinations of etoposide, cyclophosphamide, ifosfamide and,
      originally, double-dose cisplatin or, nowadays, high-dose carboplatin. The role
      of high-dose chemotherapy was studied initially in salvage and later in first
      line treatment. Four hundred thirty-six patients who received high-dose salvage
      chemotherapy have been reported, 96 (22%) of whom have obtained long-term
      complete remissions. Prognostic factors for outcome were disease status (absolute
      refractory, refractory or sensitive diseases), primary tumor site, response to
      prior chemotherapy and serum hCG levels prior to high-dose treatment. Patients
      with no adverse prognostic factors have a greater than 50% chance of cure after
      high-dose treatment. Patients with refractory disease did not benefit from high
      dose chemotherapy. A randomized European trial is ongoing to evaluate
      prospectively the role of high-dose chemotherapy in comparison to standard
      ifosfamide-based salvage treatment. In first-line consolidation treatment of poor
      risk non-seminomatous germ-cell tumors, the results of phase II trials with
      carboplatin-based high-dose therapy are in favor of a survival impact when
      compared to historical controls. A prospective randomized trial is ongoing in the
      US to study the role of carboplatin-based high-dose consolidation treatment. The
      only prospective trial comparing a cisplatin-based high-dose treatment to
      standard chemotherapy failed to demonstrate any survival advantage for the high
      dose procedure in this setting. New developments include the use of repeated
      cycles of high-dose chemotherapy with peripheral blood stem-cell support and the
      introduction of paclitaxel, a new active drug in this disease, and other non
      cross-resistant cytotoxic agents in high-dose combination regimes.

PMID- 9037357
TI  - A new challenge in clinical research in childhood ALL: the prospective meta
      analysis strategy for intergroup collaboration.
AB  - We consider the problems arising in clinical research on childhood acute
      lymphoblastic leukemia (ALL). Given the therapeutic progress achieved over the
      last few decades, any improvement in the outcome for the majority of children
      with ALL is difficult to assess with the usual size trials. Furthermore, the
      progress in genetics and molecular biology has now led to the identification of
      subgroups of children, typically with rare characteristics, for whom new
      treatments still await evaluation. For both these aspects of clinical research,
      there is an increasing need for international intergroup cooperation. After a
      discussion on the role of retrospective meta-analysis and randomized controlled
      trials in ALL research, we suggest that intergroup studies could be made more
      feasible, but still scientifically rigorous, by adopting a strategy of
      prospective meta-analysis. This strategy can be described as follows: i)
      different groups prospectively plan to ask the same randomized question within
      their protocols which may differ in other aspects, and to pool their data in
      order to evaluate treatment effect; ii) the management of the study can be de
      centralized, by allowing each group to be responsible for conducting its own
      protocol. We would like to stimulate the debate on the methodological and
      practical aspects of research perspectives in ALL (and in pediatric oncology).

PMID- 9037358
TI  - Meta-analysis and prospective meta-analysis in childhood leukemia clinical
      research.
AB  - In this paper, we consider the role of meta-analysis and 'prospective meta
      analysis' studies in childhood acute lymphocytic leukemia (ALL). In this issue,
      Valsecchi and Masera [1] give a thoughtful discourse, generally favorable to this
      approach. This article presents the opposite point of view. The aims of our
      article are to present the implications in clinical, rather than biostatistical
      terms, and to provide an extensive literature review of the subject of meta
      analysis. We conclude that treatment assessments, resulting from meta-analysis of
      closed studies (retrospective) should be met with healthy skepticism. Trials
      requiring international resources should be true intergroup trials with a single
      coordinating center, rather than prospective meta-analysis, unless it is a
      question grafted onto each group's own research agenda. For example, each group
      might ask its own systemic control question, but a CNS protection question is
      asked collectively.

PMID- 9037359
TI  - A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus
      carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk'
      metastatic non-seminomatous germ cell tumors.
AB  - BACKGROUND: Cisplatin-based combination chemotherapy will cure 70% to 80% of
      patients with metastatic non-seminomatous germ cell tumors but is associated with
      the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a
      cisplatin analogue, is an active drug in testicular cancer with a more favourable
      spectrum of side effects. In a randomized trial, the German Testicular Cancer
      Study Group compared a combination regimen of carboplatin, etoposide and
      bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy
      for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell
      tumors, according to the Indiana University classification. PATIENTS AND METHODS:
      PEB was given for three cycles at standard doses (given days 1-5), and the CEB
      regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1,
      etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four
      cycles of CEB were given, with the omission of bleomycin in the fourth cycle.
      Thus, the cumulative doses of etoposide and bleomycin applied in the two
      treatment arms were comparable. Fifty-four patients were entered on the trial, 29
      were treated with PEB and 25 with CEB chemotherapy. Patients were stratified
      according to disease extent (minimal versus moderate) and the degree of tumor
      marker elevation. Thirty-two patients (59%) belonged to the group with minimal
      disease and low markers. RESULTS: No significant difference in response to
      chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm
      and 76% for CEB treatment. However, more patients treated with CEB (32% versus
      13%) have relapsed after therapy, and 4 patients (16%) have died of disease
      progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim
      analysis of negative events (relapse, vital tumor at secondary resection, death
      from disease and therapy-associated death) showed a significantly higher rate
      after CEB than after PEB therapy, and the trial was terminated early. After a
      median follow-up of 33 months for all patients, the calculation of negative
      events is still significantly in favour of PEB-treated patient, particularly
      since three late relapses > 2 years have been observed in the CEB arm (P = 0.03).
      CONCLUSION: This randomized trial demonstrates that even with the use of adequate
      doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace
      cisplatin in patients with testicular cancer. Treatment with the PEB regimen
      remains the standard approach in patients with 'good-risk' non-seminomatous germ
      cell tumors.

PMID- 9037360
TI  - Clinical significance of bcl-2 (MBR)/JH rearrangement in the peripheral blood of
      patients with diffuse large B-cell lymphomas.
AB  - BACKGROUND: Approximately one-fourth of diffuse large B-cell lymphomas (DLCL)
      carry the bcl-2(MBR)/JH rearrangement caused by the t(14;18) translocation. The
      clinical significance of this rearrangement in patients with DLCL remains
      controversial. By polymerase chain reaction (PCR) we prospectively evaluated the
      prognostic relevance of the bcl-2 (MBR)/JH rearrangement present in circulating B
      cells at the time of diagnosis. MATERIALS AND METHODS: The bcl-2 (MBR)/JH
      rearrangement was analysed by a nested-PCR method in peripheral blood samples of
      51 HIV-negative patients with previously untreated DLCL. RESULTS: The bcl-2
      (MBR)/JH rearrangement was detected in 16 cases (31%). Peripheral blood bcl-2
      (MBR)/JH rearrangement detection by PCR at diagnosis was correlated with poor
      overall survival, lymphoma-specific survival and time to progression (log-rank P
      < 0.05). There was no statistically significant difference between the clinical
      characteristics at presentation of bcl-2/JH-positive and negative patients.
      CONCLUSIONS: The peripheral blood is a readily accessible tissue for this type of
      analysis, and this study indicates that detection of the t(14;18) translocation
      at presentation in the blood of patients with DLCL may presage a poor prognosis.

PMID- 9037361
TI  - Phase I/II trial of filgrastim (r-metHuG-CSF), CEOP chemotherapy and
      antiretroviral therapy in HIV-related non-Hodgkin's lymphoma.
AB  - BACKGROUND: A phase I/II trial determined the maximum tolerated dose (MTD) of
      CEOP for AIDS-related non-Hodgkin's lymphoma (NHL) with concurrent filgrastim and
      antiretroviral therapy. PATIENTS AND METHODS: Fourteen AIDS-NHL patients,
      chemotherapy naive and ECOG performance status < 2 received filgrastim 1.0
      microgram/kg s.c. daily for 3-7 days to assess neutrophil response, followed by
      CEOP with filgrastim support 10 micrograms/kg s.c. daily, day 2-14, continued if
      the absolute neutrophil count (ANC) < 1.2 x 10(9)/l. Two CEOP dose cohorts were
      used: cohort 1 (5 patients) - cyclophosphamide (C) 500 mg/m2, epirubicin (E) 37.5
      mg/m2, vincristine (O) 2 mg and prednisolone (P) 75 mg/m2 daily on days 1-5;
      cohort 2 (9 patients) - C 750 mg/m2, E 50 mg/m2, same doses of O and P.
      Antiretroviral therapy was maintained (zidovudine-10, ddI-3, both-1). RESULTS: In
      cohort 1, 4/5 patients received at least 3 courses of CEOP with one complete
      response after five cycles and four progressions. Four have died (3-21 months
      after entry) with 1 alive at 40 months. Dose limiting toxicity (DLT - grade IV
      febrile neutropenia in cycle 1) occurred in 1 patient. In cohort 2, 5/9 completed
      > or = 5 cycles with 6 complete responses, 1 partial response and 2 progressions,
      6 deaths and 3 alive at > 33 months. DLT (evaluable in 8 patients) occurred in
      two patients. Median survival for both cohorts was 17 months. Mean relative dose
      intensity was > 85%. CONCLUSIONS: The dosages of CEOP in cohort 1 defined the MTD
      however, the cohort 2 doses with filgrastim and antiretroviral therapy gave an
      encouraging response, acceptable toxicities and merit further study.

PMID- 9037362
TI  - Dose escalation of high-dose cyclophosphamide and etoposide with high-dose
      doxorubicin (CDE) and filgrastim for poor-risk non-Hodgkin's lymphoma.
AB  - PURPOSE: To identify the highest possible dose of cyclophosphamide (C) and
      etoposide (E) to be given with high-dose doxorubicin (D) and filgrastim (G-CSF)
      but without stem cell support in high-risk non-Hodgkin's lymphoma. PATIENTS AND
      METHODS: High-dose CDE was given to 18 evaluable patients, 5 had previous
      chemotherapy. All patients received D 90 mg/sqm and G-CSF 20 micrograms/kg/day.
      The first cohort had C 1800 mg/sqm and E 450 mg/sqm. Chemotherapy was given in
      equally divided doses over three days. Dose escalation was performed thrice up to
      C 3900 mg/sqm and E 975 mg/sqm. One to four courses were given. RESULTS: The
      median number of days (quartile values) with neutrophils < 0.5 x 10(9)/l was 9
      days (7-10), untransfused platelets < 20 x 10(9)/l 6 days (3-7), fever > or = 38
      degrees C 5 days (3-8), intravenous antibiotics 10 days (9-12), with packed red
      cell transfusion 1 day (0-2), and with platelet transfusion 2 days (1-3). Six
      patients had complete remission and 11 partial remission from first course. There
      was no difference in toxicity according to dose level. A second course was given
      to 15 patients, resulting in fewer days with neutropenia (mean 7.2), and
      intravenous antibiotics (mean 6.3). Mucositis was the main non-hematologic
      toxicity. CONCLUSIONS: Very high-dose CDE with G-CSF but without stem cell
      support is feasible as primary therapy. The toxicity was similar to that of
      standard autologous stem cell transplantation programs.

PMID- 9037363
TI  - Intensive therapy and autotransplant for patients with an incomplete response to
      front-line therapy for lymphoma.
AB  - BACKGROUND: Patients with Hodgkin's disease (HD) and intermediate or high-grade
      non-Hodgkin's lymphoma (NHL) who fail to achieve a complete remission (CR) with
      standard induction therapy have a poor prognosis with conventional-dose salvage
      therapy alone. We examined the role of subsequent intensive therapy and
      autologous bone marrow transplantation (ABMT) in patients who demonstrated a
      response to conventional-dose therapy. PATIENTS AND METHODS: Sixty-six patients
      with either HD (n = 30) or NHL (n = 36) underwent intensive therapy with
      etoposide (60 mg/kg), intravenous melphalan (160-180 mg/m2) followed by infusion
      of unpurged autologous bone marrow and/or blood cells. All patients had advanced
      stage or bulky disease at diagnosis and failed to achieve a CR after an
      anthracycline-containing front-line chemotherapy regimen (NHL) or ABVD or
      equivalent regimen (HD). Patients who achieved a CR after involved-field
      radiotherapy were excluded. All patients demonstrated sensitivity to conventional
      dose salvage treatment before advancing to intensive therapy and ABMT. RESULTS:
      The CR, partial response (PR) and overall response rate (RR) following ABMT for
      HD patients was 48%, 17% and 65%, respectively. At a median follow-up of 35
      months, the predicted three-year overall survival (OS) is 51% (95% CI: 44%-60%)
      and event-free survival (EFS) is 34% (95% CI: 26%-54%). For patients with NHL,
      the CR, PR and RR were 68%, 9% and 77%, respectively. At a median follow-up of 28
      months, the predicted three-year OS is 51% (95% CI: 35%-66%) and EFS is 39% (95%
      CI: 21%-57%). CONCLUSIONS: Intensive therapy with etoposide and melphalan
      followed by ABMT results in prolonged survival in selected patients with lymphoma
      who fail to achieve a complete remission to front-line chemotherapy. Based on our
      previous studies of outcome to conventional-dose salvage chemotherapy, we
      estimate that of all patients failing induction therapy, 28% with HD and 15% with
      NHL will be event-free at three years after ABMT.

PMID- 9037364
TI  - Mobilisation kinetics of primitive haemopoietic cells following G-CSF with or
      without chemotherapy for advanced breast cancer.
AB  - BACKGROUND: The objective of this study was to determine the optimal conditions
      for blood progenitor cell harvest for transplantation, with main emphasis on the
      mobilisation kinetics of primitive, marrow repopulating cells. PATIENTS AND
      METHODS: Sixteen patients with advanced breast cancer were treated with 4 cycles
      of dose escalating FAC chemotherapy (5-fluorouracil, adriamycin,
      cyclophosphamide) each followed by 10 micrograms/kg/d G-CSF for 13 days. We
      assessed the number of colony-forming cells (CFC), and estimated the long-term
      culture initiating cells (LTC-IC) and CD34+ cells during the recovery phase of
      cycle 1 and 4 of chemotherapy, and during additional periods of G-CSF
      administration either preceding or following the full course of chemotherapy.
      RESULTS: The highest peak numbers of CFC per ml of blood (median 10489, range 860
      39282) were mobilised after the first cycle of chemotherapy. The lowest peak
      numbers of CFC were obtained during the recovery phase from cycle 4 (median 4739,
      range 40-26789). In contrast, the numbers of CD34+ cells per ml of blood were
      significantly higher in cycle 4 (median 650, range 30-2600 x 10(2)) compared to
      those of cycle 1 (median 240, range 20-770 x 10(2)). The peak numbers of CFC
      mobilised by G-CSF before commencement and after the cessation of chemotherapy
      were equivalent, with a median of 5470 (range 1056-25669) and 5948 (range 2710
      38975) per ml of blood, respectively. However, while mononuclear cells (MNC)
      collected at the days of maximal CFC mobilization following G-CSF administration
      before or after cycle 1 were similar to normal bone marrow MNCs in their ability
      to generate haemopoiesis when seeded onto performed irradiated stroma, those
      collected after cycle 4 or during G-CSF administration after the cessation of
      chemotherapy were markedly compromised in this respect. CONCLUSIONS: Our results
      indicate that repeated cycles of FAC chemotherapy followed by G-CSF result in a
      far lower number of LTC-IC than of CFC mobilised into the circulation.
      Furthermore although the combination of chemotherapy and G-CSF mobilised the
      highest numbers if CFC, G-CSF alone pre-chemotherapy was more effective at
      mobilising LTC-IC. These data indicate that neither the numbers of CFC mobilised
      nor the numbers of CD34+ cells are necessarily a reliable indicator for the
      putative marrow repopulating capability of the blood cells mobilised with
      chemotherapy plus G-CSF.

PMID- 9037365
TI  - Pretransplant malignancy in candidates and posttransplant malignancy in
      recipients of cardiac transplantation.
AB  - BACKGROUND: Malignancy is generally considered a contraindication for cardiac
      transplantation, whereas secondary malignancy has been described under chronic
      immunosuppression. PATIENTS AND METHODS: We report here the frequency of
      malignancy encountered among the 495 patients evaluated at our cardiac transplant
      centre as well as the incidence and the course of post-transplant malignancy
      among 129 consecutive patients who underwent cardiac-transplantation, with a
      subsequent minimum follow-up of 6 months. RESULTS: A total of 10 out of 495
      patients (2%) evaluated for heart transplantation presented with a history of
      previous malignancy: 3 of them underwent transplantation (2 survive, 1 died)
      whereas in the remaining 7 patients neoplasia was considered a contraindication
      for cardiac transplantation, and all 7 died (4 cardiac, 3 tumor-related deaths).
      Post-transplant malignancy was diagnosed in 10 of 129 patients (9%) 35 +/- 15
      months after transplantation (6 skin cancers, 1 lymphoproliferative disease, 3
      solid tumors). No significant association was found between post-transplant
      malignancy and primary prophylaxis with antithymocyte globulin (ATG) or murine
      antihuman T-cell monoclonal antibodies (OKT3). CONCLUSION: These results confirm
      that pre-transplant malignancy is not an absolute contraindication for cardiac
      transplantation and that post-transplant follow-up must include careful
      monitoring of post-transplant malignancy.

PMID- 9037366
TI  - Single agent activity of oxaliplatin in heavily pretreated advanced epithelial
      ovarian cancer.
AB  - BACKGROUND: Platinum-containing chemotherapy combinations achieve high response
      rates in women with advanced ovarian cancer. Unfortunately, most patients need
      further therapeutic options. Oxaliplatin (L-OHP) is a diaminocyclohexane (DACH)
      platinum analog active against human and murine cells in vitro and in vivo,
      including ovarian cells lines, with non-cross resistance characteristics with
      first (CDDP) and second (CBDCA) generation platinum compounds. The single agent
      activity of oxaliplatin in 34 consecutive platinum-pretreated ovarian cancer
      patients, not eligible for other phase II trials, was explored in a compassionate
      use program framework in a single institution. MATERIALS AND METHODS: Thirty-five
      patients (34 of them eligible) were treated by L-OHP at the median initial dose
      of 100 mg/sqm q 3 weeks (5 patients: 58-89 mg/m2; 24 patients: 90-100 mg/m2; 6
      patients: 120-130 mg/m2) by short (30'-2 hours) i.v. infusion; the treatment was
      repeated every three weeks until treatment limiting toxicity or disease
      progression. RESULTS: Thirty-one patients (median previous chemotherapy lines: 3)
      were evaluable for antitumoral activity, with a 29% objective response rate.
      According to Markman's criteria, objective partial responses were seen in six out
      of 13 evaluable potentially platinum-sensitive patients (46%) and three responses
      in the 18 evaluable platinum-resistant patients (17%). The tolerance was
      excellent, with no grade 3-4 (WHO) leukoneutropenia despite previous ABMT and
      abdominopelvic radiotherapy in six and eight cases, respectively. There was no
      renal or ototoxicity, and nausea/vomiting were moderate. The only grade 3 (WHO)
      peripheral neuropathy recorded concerned a patient with a neurotoxicity status
      grade 2 at baseline. CONCLUSION: The 29% ORR single agent activity of oxaliplatin
      at hematological subtoxic doses in heavily pretreated ovarian cancer patients,
      with objective responses in platinum refractory patients, supports experimental
      data on non cross-resistance and a differential clinical toxicity profile to
      other available platinum compounds. The 12 month median overall survival of this
      poor prognosis patients cohort (62% platinum-refractory patients, median number
      of three previous chemotherapy lines) gives a strong empirical basis for the
      further exploration of oxaliplatin's role in confirmatory phase II and
      combination chemotherapy studies.

PMID- 9037367
TI  - Meningeal localization in a patient with Hodgkin's disease. Description of a case
      and review of the literature.
AB  - We report the case of a 21-year-old man in whom intracranial localization was
      discovered during initial staging at the onset of Hodgkin's disease (HD). The
      patient was treated by surgical excision, irradiation and chemotherapy and 50
      months after completion of therapy is in remission with no evidence of HD. A
      brief review of the literature regarding 48 patients with intracranial Hodgkin's
      disease is presented.

PMID- 9037368
TI  - A phase I study of bi-weekly paclitaxel/cisplatin as initial therapy for advanced
      ovarian cancer. A study of the National Cancer Institute of Canada Clinical
      Trials Group.
AB  - PURPOSE: Given the potential for improved outcomes, a phase I trial was initiated
      to develop a paclitaxel/cisplatin regimen that could be delivered every two weeks
      to women with newly diagnosed advanced ovarian cancer. PATIENTS AND METHODS: From
      1992 to 1994, 29 (28 eligible) patients were enrolled in a dose-seeking trial.
      All received 60 mg/m2 of cisplatin preceded by paclitaxel infused over three
      hours. The paclitaxel dose was excalated from an initial level of 90 mg/m2 by 10
      mg/m2 increments in successive cohorts of patients. RESULTS: At 120 mg/m2 of
      paclitaxel, the dose-limiting toxicity was granulocytopenia which prevented
      retreatment on time. The recommended dose level was therefore paclitaxel 110
      mg/m2 infused over three hours with cisplatin 60 mg/m2, repeated bi-weekly for
      eight cycles. CONCLUSION: This bi-weekly schedule of paclitaxel/cisplatin
      provides no advantage in terms of dose-intensity nor total dose of paclitaxel in
      comparison to more common regimens given tri-weekly.

PMID- 9037369
TI  - Phase II study of a closely spaced ifosfamide--cisplatin schedule with the
      addition of G-CSF in advanced non-small-cell lung cancer and malignant melanoma.
AB  - BACKGROUND: Ifosfamide and cisplatin are frequently combined cytotoxic agents.
      Both have a dose-response relationship. In view of this it appears attractive to
      study regimens with a higher dose intensity than usual. One way to increase the
      dose intensity is to shorten intervals between chemotherapy cycles. As bone
      marrow toxicity is dose limiting in ifosfamide-cisplatin combinations we started
      a phase II study with both drugs administered every 2 weeks in combination with G
      CSF. PATIENTS AND METHODS: Patients with advanced non-small-cell lung cancer or
      malignant melanoma were eligible for the study. The treatment consisted of
      ifosfamide 2 gram/m2/day days 1-3 combined with mesna, and cisplatin 33 mg/m2/day
      days 1-3, administered in hypertonic saline (3% NaCl). G-CSF was started on day 4
      at a dose of 5 micrograms/kg/day and was continued until day 12. The cycles were
      to be repeated every 2 weeks for a maximum of 6 cycles. RESULTS: Thirty-two
      patients were entered in the study; 30 patients were evaluable for response and
      toxicity. Neutropenia (grade 4 in 16 patients) and thrombocytopenia (grade 4 in
      15 patients) were the most common toxicities. Thrombocytopenia incidence and 
      duration increased per cycle and was the main cause of treatment delays
      especially after the third cycle. Only 4 patients were able to complete the
      planned treatment without any delay or dose reduction and reached the intended
      dose intensity of 3 gram/m2/week of ifosfamide and 50 mg/m2/week of cisplatin.
      Non haematologic toxicities were generally mild. Out of 22 evaluable patients
      with non-small cell lung cancer 6 responded (27%; 95% CI: 10%-48%) while only one
      out of 8 patients with melanoma responded. The median response duration was 26
      weeks (range 16-36 weeks). CONCLUSION: The planned high-dose intensity of
      ifosfamide and cisplatin could be reached only for the first 2-3 cycles.
      Haematologic toxicity, especially cumulative thrombocytopenia, necessitated
      treatment delays jeopardizing the dose intensity. The response rate in non-small
      cell lung cancer and melanoma was not superior to what can be expected from more
      conventional regimens.

PMID- 9037370
TI  - Preliminary experience with paclitaxel for the treatment of relapsed and
      refractory Hodgkin's disease.
AB  - PURPOSE: To determine the activity of paclitaxel (Taxol; Bristol-Myers Squibb
      Co., Princeton, NJ) in patients with relapsed and primary treatment-refractory
      Hodgkin's disease. PATIENTS AND METHODS: Fifteen patients with relapsed (n = 8)
      or primary treatment-refractory (n = 7) Hodgkin's disease were treated at two
      cancer centers. Patients received paclitaxel 200 mg/m2 intravenously over three
      hours every three weeks. All patients also received premedication with
      dexamethasone, cimetidine, and diphenhydramine. The median age was 33 years
      (range 19 to 69 years), and the median number of prior treatment regimens was
      three. Seven patients had previously received treatment with autologous bone
      marrow transplantation. RESULTS: Fourteen patients were evaluable for response
      after receiving one to six courses (median, two courses) of paclitaxel. Two
      patients (14%) had partial remissions; both of them had relapsed after achieving
      a complete remission with high-dose therapy and autologous bone marrow
      transplantation. One of these patients was given involved field radiation to
      consolidate the partial remission and remains free of disease two years after
      paclitaxel therapy. Three patients had stable disease, and nine had progressive
      disease. Therapy was well tolerated, with a toxicity profile similar to that
      previously reported for paclitaxel in patients with non-Hodgkin's lymphoma.
      CONCLUSION: Paclitaxel, at this dose and schedule, has modest activity in this
      group of heavily pretreated patients. Studying its activity in patients with more
      favorable disease characteristics is warranted.

PMID- 9037371
TI  - Cellular factors as alternative targets for inhibition of HIV-1.

PMID- 9037373
TI  - Antiviral effects of 6-diazo-5-oxo-L-norleucin on replication of herpes simplex
      virus type 1.
AB  - An L-glutamine antagonist, 6-diazo-5-oxo-L-norleucin (L-DON), inhibits
      replication of vesicular stomatitis virus, poliovirus and paramyxoviruses in
      cultured cells. We tested the antiviral activity of L-DON against different
      strains of herpes simplex virus type 1 (HSV-1) in Vero cells. In the presence of
      a physiological plasma concentration of L-glutamine (0.5mM) L-Don inhibited 50%
      production of virus plaques at concentrations ranging from 7.9 to 16 microM. At
      concentrations of 40 microM L-Don inhibited infectious virus yield by 99%. The
      antiviral activity of L-DON decreased with increasing L-glutamine concentrations.
      A concentration of 5000 microM of L-Don had no significant effects on the
      viability of Vero cells. Transmission electron microscopical investigations
      showed that L-DON prevented mainly envelopment of viral nucleocapsids in the
      cytoplasm. The immunoprecipitation experiments demonstrated selective inhibition
      of synthesis of HSV-1 glycoproteins in L-DON treated cells. The results showed
      that L-DON inhibits HSV-1 replication at a late stage in the virus replication
      cycle, probably the cytoplasmic maturation of virions and subsequent virion
      egress from the cells.

PMID- 9037372
TI  - Red blood cells mediated delivery of 9-(2-phosphonylmethoxyethyl)adenine to
      primary macrophages: efficiency metabolism and activity against human
      immunodeficiency virus or herpes simplex virus.
AB  - Red blood cells (RBC) may act as selective carriers of drugs to macrophages, an
      important reservoir of viruses such as human immunodeficiency virus (HIV) and
      herpes simplex virus type 1 (HSV-1). We therefore assessed the incorporation of 9
      (2-phosphonylmethoxyethyl)adenine (PMEA), a potent inhibitor of HIV and HSV-1)
      into RBC, its delivery to macrophages and its activity against HIV or HSV-1.
      Loading of PMEA in artificially aged opsonized RBC affords significant levels of
      intracellular PMEA. RBC metabolize PMEA to its active congener PMEA-diphosphate,
      although with low efficiency. Exposure of macrophages to RBC-encapsulated PMEA
      inhibits the replication of both HIV and HSV-1 (about 90% inhibition at the
      highest RBC:macrophages ratios) even if RBC were removed before virus challenge.
      By contrast, the antiviral activity of free PMEA removed before virus challenge
      was irrelevant at concentrations up to 150-fold higher than the 50% effective
      concentration (EC50). Finally, the antiviral effect of RBC-encapsulated PMEA
      correlates with PMEA levels in macrophages about 500-fold higher than those
      achieved by free PMEA (at concentrations 10-fold higher than the EC50). The
      efficacy of RBC-mediated delivery to macrophages of PMEA (and perhaps of
      compounds with shorter intracellular half-lives) warrants further studies in
      infectious diseases involving phagocytizing cells as main targets of the
      pathogen.

PMID- 9037374
TI  - Neuramide inhibits Epstein-Barr virus-induced transformation activity and
      proliferation of transformed B lymphocytes.
AB  - Neuramide, in Italy, is a prescription drug and contains various polypeptides,
      with molecular weights ranging between 10,000 and 1,000. It is commonly used in
      Italy for the clinical therapy of varicella-zoster and other viral herpetic
      diseases. In the present study, we investigated its effect on the in vitro
      transformation activity and transformed status of the Epstein-Barr virus (EBV),
      ab herpesvirus closely associated with infectious mononucleosis (IM),
      nasopharyngeal carcinoma (NPC) and Burkitt's lymphoma (BL). Antiviral effects of
      neuramide were evaluated on viral-induced immortalization, transformed status and
      DNA synthesis. Our results show that simultaneous and/or post-treatment of EBV
      infected lymphocytes with neuramide, at a concentration of 2 inhibiting units
      (IU)/ml, blocks EBV-mediated transformation and related events, whereas
      pretreatment does not show any inhibiting activity against EBV. Neuramide was
      also found to be a potent inhibitor of the proliferation of EBV-transformed B
      lymphocytes in vitro. These results suggest that the molecular mechanisms of
      action of the drug should be investigated more closely and also support the
      necessity to further purify the active polypeptides, in order to improve its
      possible in vivo efficacy in EBV-associated diseases, such as infectious
      mononucleosis and other lymphoproliferative diseases.

PMID- 9037375
TI  - The synthesis and immunogenicity of varicella-zoster virus glycoprotein E and
      immediate-early protein (IE62) expressed in recombinant herpes simplex virus-1.
AB  - In order to evaluate the conditions for optimal expression and immunogenicity of
      varicella-zoster virus (VZV) proteins in a herpes simplex virus-1 (HSV-1) vector,
      we selected the VZV glycoprotein E (gE), encoded by ORF 68 and the VZV product of
      ORF 62, an immediate-early major tegument protein (IE62). Three HSV/VZV
      recombinants were generated: (1) VZV gE protein coding sequences along with the
      promoter region were inserted into the thymidine kinase (TK) gene of HSV-1 strain
      KOS; (2) VZV gE expressed from the HSV-1 ICP4 promoter was inserted into the
      glycoprotein C (gC) gene of HSV-1 strain F; and (3) VZV IE62 protein coding
      sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC
      gene of HSV-1 strain F. Immunoblot analysis and immunoperoxidase staining of
      infected cell monolayers demonstrated vector expression of VZV proteins.
      Following intracranial inoculation in mice, both VZV gE-HSV (TK) and VZV IE62-HSV
      (gC) induced an IgG response against VZV gE or VZV IE62. When tested in
      cytotoxicity assays using T-lymphocytes from VZV immune human donors, the range
      of precursor frequencies for T-lymphocytes that recognized VZV gE or VZV IE62 was
      similar whether these proteins were expressed by HSV-1 or a vaccinia vector.
      These experiments demonstrate that HSV-1 is a competent vector for expression of
      these VZV proteins and support the feasibility of engineering a combined vaccine
      for these closely related alpha-herpesviruses.

PMID- 9037376
TI  - Inhibition of respiratory syncytial virus replication by antisense
      oligodeoxyribonucleotides.
AB  - Oligodeoxyribonucleotides targeted against respiratory syncytial virus (RSV)
      genomic RNA inhibited RSV replication in cell culture by an apparent antisense
      mechanism. HEp-2 cells were infected with RSV strain A2 and incubated in the
      presence of oligonucleotides. Virus replication was measured by enzyme-linked
      immunosorbent assay (ELISA), virus yield assay, or production of specific RSV
      mRNAs. Using ELISA, 50% effective concentration (EC50) values were about 0.5-1
      microM for an antisense oligonucleotide targeted to the start of the NS2 gene.
      All oligonucleotides inhibited virus antigen production as measured by ELISA. In
      all assays, this antisense oligonucleotide was more potent than: (1) a control
      oligonucleotide containing the reverse sequence; (2) oligonucleotides targeted at
      RSV mRNA; (3) a random sequence oligonucleotide; and (4) ribavirin. Reverse
      transcriptase polymerase chain reaction (PT-PCR) showed sequence specific
      depletion of the genomic RNA target following treatment of cells with the
      antisense oligonucleotide. Specific cleavage of the genomic target RNA has been
      detected at the antisense oligonucleotide binding site, suggesting that cellular
      Rnase H participates in the reaction. These results indicate that antisense
      oligonucleotides targeted against RSV genomic RNA can effectively inhibit RSV
      replication and may have therapeutic value.

PMID- 9037377
TI  - Comparison of human cytomegalovirus (HCMV) protease sequences among laboratory
      strains and seven clinical isolates.
AB  - The nucleotide sequence of the human cytomegalovirus (HCMV) protease gene from
      two laboratory strains and seven clinical isolates, both ganciclovir-sensitive
      and -resistant, was examined to determine the genetic variability of the HCMV
      protease catalytic domain and to identify changes that may alter the efficacy of
      designed protease inhibitors. The Towne strain varied from AD169 at 12
      nucleotides and led to one amino acid change at position 12 (Ala to Thr). The
      clinical isolates had amino acid substitutions relative to the laboratory
      strains, with a Ser to Pro change at position 8, a His to Tyr change at position
      44 and s Gly to Ser change at position 47. None of these changes occurred in any
      of the conserved domains of the protease, nor do they appear necessary to confer
      ganciclovir resistance in the isolates. These findings suggest that no changes
      exist in the protease of the clinical isolates examined that may diminish the
      effectiveness of a drug targeting the HCMV protease. 1977 Elsevier Science B.V.
      All rights reserved.

PMID- 9037378
TI  - Local renin-angiotensin system: especially in coagulating glands of mice.
AB  - It is well known that the renin-angiotensin system (RAS) is involved in the
      control of blood pressure. Recently, all or part of the components concerning the
      RAS have been reported to be synthesized and secreted outside of classical organs
      or tissues, at sites including the brain, pituitary and pineal glands, eye,
      heart, adrenal gland, testes, ovary, placenta, and coagulating glands. The
      functions and roles of these local RAS are not well known. In the present review,
      the author explains the history of the RAS, the circulating RAS and the existence
      of local RAS in multiple organs and tissues, discussing especially the function
      of coagulating gland renin. Renin protein, the triggering enzyme of the RAS, is
      distributed generally in certain fixed cells of several organs and tissues,
      exemplified by the gonadotrops in the pituitary glands and Leydig cells in the
      testis. Renin mRNA and its expressing cells can also be detected from the above
      cells as a whole. In some tissues, angiotensinogen-containing cells do not,
      however, correspond to its mRNA-expressing cells and potent activator angiotensin
      II-containing cells, as, for example, in the brain. These cases are explained by
      constitutive pathways of angiotensinogen processing. Coagulating gland renin,
      which the author is investigating vigorously, is the most recently discovered
      local renin, and represents significant subject for investigations. It is
      suggested that coagulating gland renin may play an unique function for sexual
      organs by exocrine mechanism.

PMID- 9037379
TI  - Atomic force microscopy in histology and cytology.
AB  - This review briefly introduces the principles of the atomic force microscope
      (AFM) and shows our own results of AFM application to biological samples. The
      AFM, invented in 1986, is an instrument that traces the surface topography of the
      sample with a sharp probe while monitoring the interaction forces working between
      the probe and sample surface. Thus, the AFM provides three-dimensional surface
      images of the sample with high resolution. The advantage of the AFM for
      biologists is that AFM can visualize non-conductive materials in a non-vacuous
      (i.e., air or liquid) environment. AFM images of the plasmid DNA are comparable
      to those by transmission electron microscopy using a rotary shadowing technique,
      and have the advantage of examining directly the molecule without staining nor
      coating. The surface structure of human metaphase chromosomes and mouse collagen
      fibrils demonstrated in air by the non-contact mode AFM is comparable to that
      obtained by scanning electron microscopy. Quantitative information on the heights
      of structures is further obtainable from the AFM images. Embedment-free thin
      tissue-sections are useful for observing intracellular structures by AFM. The
      present review also shows AFM images of living cultured cells which have been
      collected in a contact mode in liquid. This technique afforded us three
      dimensional observation of the cellular movement with high resolution. Although
      there are some innate limitations for AFM imaging, the AFM has great potential
      for providing valuable new information in histology and cytology.

PMID- 9037380
TI  - Immunohistochemical studies on protein gene product 9.5, serotonin and
      neuropeptides in vallate taste buds and related nerves of the guinea pig.
AB  - The occurrence, distribution and innervation of guinea pig vallate papillae were
      investigated by means of indirect immunofluorescence and immunoperoxidase methods
      using antibodies against: a neuron-specific protein, protein gene product 9.5
      (PGP 9.5); various neuropeptides including calcitonin gene-related peptide
      (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) and galanin; a
      monoamine, serotonin (5-hydroxytryptamine; 5HT). Numerous PGP 9.5-immunoreactive
      nerve fibers were found to form plexuses in the lingual epithelium both
      intragemmally and extragemmally and to comprise dense bundles in the lamina
      propria just beneath the epithelium. Moderate numbers of PGP 9.5-immunoreactive
      cells were observed in the taste buds. These cells, typically spindle in shape,
      extended through the entire thickness of the taste bud. CGRP-immunoreactive nerve
      fibers were numerous in the subgemmal connective tissue and entered the
      epithelium to form intragemmal and extragemmal networks. A dense subgemmal SP
      immunoreactive network in the vallate papilla can be linked to the presence of
      taste buds, even though SP-immunoreactive nerve fibers rarely occurred
      intragemmally. No taste cells immunoreactive for CGRP and for SP were observed.
      Immunoreactivity for VIP or galanin was not detected in nerve fibers and taste
      cells. In contrast, some taste cells and a few, fine networks of nerve fibers in
      the connective tissue were immunoreactive for 5HT; none of the intraepithelial
      fibers were 5HT-immunoreactive. We suggest that: 1) functionally, 5HT-containing
      cells and the CGRP-containing nerve fibers may be primarily involved in the
      neural transmission or its modulation of the taste sensation; and 2) VIP and
      galanin can be excluded from that group of substances which plays important roles
      in taste sensation.

PMID- 9037381
TI  - Changes in adhesion molecule expression during distinct patterns of immune cell
      migration in the inflamed lung.
AB  - In response to antigen inhalation, immune cells including alveolar macrophages
      expressing a VIP1 receptor subtype (VIP1R), lymphocytes and leukocytes
      participate in the inflammatory event, migrating into and from vascular regions
      in lung tissue of sensitized mice. To analyze these migratory mechanisms of
      immune cells, we immunohistochemically examined the expression of the following:
      cellular adhesion molecules, lymphocyte function-associated antigen-1 (LFA-1)
      very late activation antigen-4 (VLA-4), and the alpha V (alpha v) subunit and
      their respective ligands, intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1), and fibronectine; the examination was carried
      out in pulmonary tissue from days 0, 2, 6 and 12 following intratracheal
      administration of sheep red blood cells (SRBC) as an antigen to previously
      sensitized mice. Two days following the antigen challenge, VIP1R-positive
      macrophages strongly expressing the alpha v integrin subunit were found clustered
      on the endothelial surface and among the aggregates of perivascularly infiltrated
      leukocytes. On the endothelium of arteries, veins and capillaries, alpha v
      immunoreactivity was prominently reduced, whereas staining for fibronectin was
      enhanced more than the prechallenge control level. The blood vessel endothelium
      was also stained positive for VCAM-1 and ICAM-1, while many of the infiltrating
      lymphocytes were positive for VLA-4 and LFA-1 immunolabelings. By post-challenge,
      day 6, delta v integrin subunit immunoreactivity was re-expressed on the blood
      vessel endothelium and only weakly expressed on VIP1R-positive macrophages, which
      were in retreat from the leukocyte-aggregating perivascular region and located in
      the alveoli. VLA-4 bearing lymphocytes conspicuously increased in number among
      the perivascular leukocytes, while immunoreactivity for LFA-1, VCAM-1, ICAM-1 and
      fibronectin was unchanged from that for post-challenge day 2. The results
      indicate that the expression of the alpha v-bearing integrin and its ligand
      fibronectin drastically changes as pulmonary inflammatory responses. These
      changes in expression of adhesion molecules during immune response may play an
      important role in the dynamic regulation of VIP1R-positive macrophage migration
      in the lung parenchymal compartment.

PMID- 9037382
TI  - The intercalated disc of monkey myocardial cells and Purkinje fibers as revealed
      by scanning electron microscopy.
AB  - The intercalated discs of working myocardium and Purkinje fibers of the monkey
      heart were examined by scanning and transmission electron microscopy. The
      NaOH/ultrasonication technique resulted in the digestion of connective tissue and
      a separation of the intercellular junctions of intercalated discs, such that
      these could be visualized three-dimensionally. The intercalated discs of
      ventricular myocytes, atrial myocytes and Purkinje fibers vary considerably in
      number and configuration, as do the intercalated discs of the three different
      layers of the ventricular myocardium. Myocytes in the subepicardial, middle and
      subendocardial layers of the ventricle have 1-3, 4-5 and 5-6 intercalated discs
      at the end of these cells, respectively. Those in the endocardial layer are
      characterized by the presence of small laterally-placed intercalated discs.
      Atrial myocytes and Purkinje fibers usually only have 1-2 intercalated discs.
      Individual intercalated discs in ventricular myocytes have complicated stairs
      with 10-30 steps and corresponding risers, while those of atrial myocytes and
      Purkinje fibers have simple stairs with 1-3 steps and risers. Steps equivalent to
      the plicate segments are characterized by densely-packed microplicae and finger
      like microprojections which greatly increase surface area in ventricular
      myocytes. Microprojections in atrial myocytes and Purkinje fibers are sparse by
      comparison. Risers equivalent to the interplicate segments containing large gap
      junctional areas are most numerous in left ventricular myocytes, followed by
      right ventricular myocytes, Purkinje fibers and atrial myocytes in decreasing
      order. The geometric arrangement of the various types of myocytes may be related
      with impulse propagation. Large intercalated discs of cell trunks and series
      branches may participate in longitudinal propagation, while small laterally
      placed ones may be the site of transverse propagation.

PMID- 9037383
TI  - Histochemical study of follicles in the senescent porcine pituitary gland.
AB  - Follicles displaying a positive periodic acid-Schiff reaction to a colloid
      substance in the anterior pituitary gland have been observed in many vertebrates,
      including humans. It is also known that these follicles greatly increase in
      number and size with age. We therefore performed histochemical analysis of these
      colloid follicles in the senescent porcine pituitary gland in order to clarify
      their nature and biological significance. Results from various histological
      stains suggest that the colloid contains some polysaccharides or glycoproteins.
      In addition to the histological stains, lectin histochemistry revealed that the
      colloid contains sialic acid, N-acetyl galactosamine and galactose. Also, lectin
      staining indicated that some glycoproteins, most likely Asn-linked
      sialoglycoproteins, are localized in the colloid. The cells (FS cells)
      surrounding the colloid were densely stained with an antibody to S-100 protein
      but were not stained with antibodies to any other anterior pituitary hormones.
      Frequently mammotrophs (PRL cells), and occasionally gonadotrophs (LH cells) were
      found closely associated with folliculo-stellate cells (FS cells which lay next
      to the large colloid containing follicles. This suggests that not only are the FS
      cells important in the production of the colloids, but the adjacent LH and PRL
      cells in some way also contribute to their formation.

PMID- 9037384
TI  - A possibility of efferent innervation of the gustatory cell in the rat
      circumvallate taste bud.
AB  - A transmission-electron microscope study of the rat circumvallate taste bud
      revealed that occasionally one and the same gustatory or Type III cell received
      innervation associated with subsurface cisterns as the Type II cell did, in
      addition to the ordinary afferent synapse. The subsurface cistern a flattened,
      smooth-surfaced saccular membrane system, hugged the plasma membrane of the
      gustatory cell along the boundary against the nerve terminal. The nerve terminal
      attaching to the cell was occupied with mitochondria and synaptic type vesicles.
      As these structural features resemble those of efferent synapses in certain other
      sensory cells including the inner ear hair cells, the gustatory cells dually
      innervated as demonstrated in the present study are presumably involved not only
      in the afferent but also in the efferent projection of nerves.

PMID- 9037385
TI  - Cellular distribution of the P2X4 ATP receptor mRNA in the brain and non-neuronal
      organs of rats.
AB  - RNA blot analysis has shown that an ionotropic ATP receptor P2X4 is widely
      distributed, as compared with other P2X subtypes. Cellular distribution of the
      P2X4 ATP receptor mRNA was investigated by in situ hybridization technique in the
      brain and non-neuronal organs. In the brain, transcripts of the P2X4 were widely
      distributed in various regions, with the highest signals in the cerebellar
      Purkinje cells and granule cells. In other organs, intense and selective
      expression was detected in seminiferous tubules of the testis and intestinal
      crypts of the colon, suggesting an involvement of ATP in spermatogenesis and
      intestinal secretion. A low but significant level of the P2X4 mRNA was detected
      in the adenohypophysis and the cortex of the adrenal gland. The tissue- or cell
      specific expression of the P2X4 mRNA is of importance to understand the
      functional roles of the purinergic transmission system.

PMID- 9037386
TI  - Distribution and origins of nitric oxide-producing nerve fibers in the dog
      tongue: correlated NADPH-diaphorase histochemistry and immunohistochemistry for
      calcitonin gene-related peptide using light and electron microscopy.
AB  - The distribution and origins of nitric oxide (NO)-producing nerves in the dog
      tongue with reference to calcitonin gene-related peptide (CGRP)-containing
      sensory fibers were investigated using NADPH-diaphorase (NADPH-d) histochemistry
      and immunohistochemistry for CGRP and NO synthase combined with retrograde axonal
      tracing and denervation experiments. The ultrastructural relationships between
      NADPH-d-positive and CGRP-immunoreactive neuronal elements were also examined
      electron microscopically. NADPH-d-positive and CGRP-immunoreactive varicose
      fibers were found within the taste buds and surrounding the epithelia of the
      fungiform papillae, and they disappeared completely after severance of the
      lingual nerve. Following injection of fast blue into the subepithelial layer of
      the anterior two thirds of the tongue, retrogradely labeled neurons possessing NO
      synthase and/or CGRP immunoreactivities were mainly detected in the trigeminal
      ganglion. Some of the retrogradely labeled trigeminal cells showed the
      coexistence of NADPH-d reactivity and CGRP immunoreactivity, but in the
      geniculate ganglion neither NADPH-d reactivity nor NO synthase immunoreactivity
      was found instead of retrogradely labeled CGRP-immunoreactive neurons. The
      lingual artery and its branches, including the arteriovenous anastomoses, showed
      dense distributions of NADPH-d-positive fibers, most of which were unaffected by
      the denervation experiments. There were many small ganglia in the tongue, and
      virtually all ganglionic neurons were NADPH-d reactive. CGRP-immuno-reactive
      varicose fibers were also found around the vascular walls and within the
      intralingual ganglia. Ultrastructural analysis revealed a close distribution of
      NADPH-d-positive and CGRP-immunoreactive varicose fibers within the arterial
      walls, and synaptic contacts between CGRP-immunoreactive terminals and NADPH-d
      positive intralingual ganglionic neurons. These results indicated that the taste
      buds of epithelia of fungiform papillae in the anterior two thirds of the dog
      tongue receive NADPH-d-positive and CGRP-immunoreactive sensory fibers from the
      trigeminal ganglion, and that perivascular NADPH-d-positive fibers mainly
      originate from intrinsic ganglia in the tongue. The ultrastructural findings
      suggest an intrinsic peripheral nerve-reflex mechanism in the regulation of the
      lingual vascular function by NO-producing postganglionic parasympathetic neurons
      and CGRP-containing sensory fibers.

PMID- 9037387
TI  - Localization of glycosaminoglycans and CD44 in the human lacrimal gland.
AB  - Recent analyses of tears indicate the presence of glycosaminoglycans as their
      components, but their origin remains unknown. To further understand the origin of
      these tear components, we investigated by immunohistochemical techniques the
      localization of glycosaminoglycans and CD44 human lacrimal glands obtained from
      20 cadavers at autopsy. Monoclonal antibodies to CD44, a receptor for hyaluronic
      acid, dermatan sulfate, chondroitin sulfate, and keratan sulfate were applied to
      the tissue. Hyaluronic acid binding region was also used for the staining of
      hyaluronic acid. By light microscopy, immunoreactivity for CD44 was mostly
      detected on the baso-lateral membrane of acinar and ductal cells, and the
      vascular endothelium in the interstitium. Positive staining of hyaluronic acid
      was associated intensely with the basal membrane of acinar and ductal cells and
      weakly, faintly or not at all with their lateral membrane. Positive staining of
      hyaluronic acid and immunoreactivity for dermatan sulfate were detected in
      interstitial fibrous structures; particularly, the former was intense in the
      perivascular fibrous structures, and the latter along the periparenchimal fibrous
      structures. Immunoreactivity for chondroitin sulfate and keratan sulfate was seen
      in some acinar cells and the acinar and ductal lumen. By electron microscopy,
      immunogold particles indication chondroitin sulfate sulfate or keratan sulfate
      labeled secretory granules of the acinar cells. Considering the fact that CD44 is
      a receptor molecule for hyaluronic acid, the association of hyaluronic acid with
      the basal membrane and weakly or faintly with the lateral membrane of acinar and
      ductal cells may be attributed to the expression of CD44 on the baso-lateral
      membrane of the cells. Moreover, the presence of immunoreactivity for chondroitin
      sulfate and keratan sulfate in secretory granules of acinar cells and their
      lumens suggests that tears from the lacrimal gland contain these
      glycosaminoglycans.

PMID- 9037389
TI  - [125I]4-aminobenzyl-5'-N-methylcarboxamidoadenosine (125I)AB-MECA) labels
      multiple adenosine receptor subtypes in rat brain.
AB  - Adenosine modulates neuronal activity and neurotransmitter release through
      interaction with cell surface receptors. Four adenosine receptor subtypes, A1,
      A2A, A2B, and A3 receptors, have been cloned and characterized. The agonist
      ligand, [125I]AB-MECA ([125I]4-aminobenzyl-5'N-methylcarboxamidoadenosine) has
      high affinity for recombinant A1 and A3 receptors [Olah et al., Mol. Pharmacol,
      45 (1994) 978-982]. Rodent A3 receptors are relatively insensitive to xanthines;
      inhibition of A1 receptors with xanthines allows selective detection of A3
      receptors despite the lack of selectivity of the ligand. We studied whether
      [125I]AB-MECA is useful for localization and characterization of A3 receptors in
      rat brain. The autoradiographic distribution of total [125I]AB-MECA (400 pM)
      binding closely resembled the pattern of A1 receptor binding, with highest levels
      in cerebellum, hippocampus, and thalamus, and moderate levels in cortex and
      striatum. Drug competition studies confirmed that almost all [125I]AB-MECA
      binding could be attributed to labeling of A1 receptors. Xanthine amine congener
      (1 microM) reduced specific [125I]AB-MECA binding by > 95%, indicating that
      xanthine-resistant A3 receptors represent a quantitatively minor subtype. Despite
      the use of a radioligand with high affinity and high specific activity, the low
      density of A3 receptors in rat brain appears insufficient to allow localization,
      or even consistent detection, of this receptor subtype. In the presence of DPCPX
      (50 nM, to block A1 receptors), residual [125I]AB-MECA binding to A2A receptors
      was observed in the striatum. Thus [125I]AB-MECA labels primarily A1 and A2A
      adenosine receptors in rat brain.

PMID- 9037388
TI  - Low-affinity sulfonylurea binding sites reside on neuronal cell bodies in the
      brain.
AB  - The antidiabetic sulfonylurea drugs bind to sites associated with an ATP
      sensitive potassium (Katp) channel on cell bodies and terminals of neurons which
      increase their firing rates or transmitter release when glucose concentrations
      rise or sulfonylureas are present. High-affinity sulfonylurea binding sites are
      concentrated in areas such as the substantia nigra (SN) where glucose and
      sulfonylureas increase transmitter release from GABA neurons. But there is a
      paucity of high-affinity sites in areas such as the hypothalamic ventromedial
      nucleus (VMN) where many neurons increase their activity when glucose rises. Here
      we assessed both high- and low--affinity sulfonylurea binding
      autoradiographically with 20 nM [3H]glyburide in the presence of absence of
      Gpp(NH)p. Neurotoxin lesions with 6-hydroxydopamine (6-OHDA), 5,7
      dihydroxytryptamine (5,7-DHT) and ibotenic acid were used to elucidate the
      cellular location of the two sites in the VMN, SN and locus coeruleus (LC). In
      the VMN, 25% of the sites were of low affinity. Neither 6-OHDA nor 5,7-DHT
      affected [3H]glyburide binding, while ibotenic acid reduced the number of VMN
      neurons and abolished low-affinity without changing high-affinity binding. In
      cell-attached patches of isolated VMN neurons, both 10 mM glucose and 100 microM
      glyburide decreased the open probability of the Katp channel suggesting that the
      low-affinity binding site resides on these neurons. In the SN pars reticulata,
      ibotenic acid reduced the number of neurons and high-affinity [3H]glyburide
      binding was decreased by 20%, while 6-OHDA had no effect. In the SN pars
      compacta, both 6-OHDA and ibotenic acid destroyed endogenous dopamine neurons and
      selectivity ablated low-affinity binding. In the LC, 6-OHDA destroyed
      norepinephrine neurons and abolished low-affinity binding. These data suggest
      that low-affinity sulfonylurea binding sites reside on cell bodies on VMN, SN
      dopamine and LC norepinephrine neuron cell bodies and that high-affinity sites
      may be on axon terminals of GABA neurons in the SN.

PMID- 9037390
TI  - The association of tissue transglutaminase with human recombinant tau results in
      the formation of insoluble filamentous structures.
AB  - To determine possible mechanisms by which NFTs are formed in Alzheimer's disease
      (AD), we investigated the ability of tissue transglutaminase (TGase) to convert
      human recombinant tau proteins into insoluble filamentous structures. TGase
      derived from guinea pig liver was activated by calcium to catalyze the in vitro
      cross-linking of the largest soluble recombinant tau isoform (htau40) into
      insoluble complexes as determined by electrophoresis following incubation in 4 M
      urea and SDS. The TGase-catalyzed formation of these insoluble complexes occurred
      within 15 min to 24 h and the decreased migration of the insoluble material
      correlated with increased calcium concentrations ranging from 2 mM to 50 mM when
      analyzed electrophoretically. TGase-treated human recombinant tau formed
      filamentous structures in vitro that were immunoreactive with antibodies to tau
      and TGase. These structures retained the insoluble characteristics typical of AD
      PHF/NFTs. Immunolabeling with the TGase antibody revealed that TGase is
      associated with the filaments formed from human recombinant tau in vitro as well
      as with PHFs isolated from NFTs from AD brains. These novel findings support an
      in vitro model for investigating the biophysical changes that occur in converting
      soluble tau proteins into an insoluble matrix consistent with the insoluble
      PHFs/NFTs which may contribute to neuronal degeneration and cell death in the AD
      brain.

PMID- 9037391
TI  - Ganglioside composition of the human cranial nerves, with special reference to
      pathophysiology of Miller Fisher syndrome.
AB  - Total ganglioside fractions from the human cranial nerves purified on a Phenyl
      Sepharose column, were given mild alkaline treatment, after which their
      composition and amounts of lipid-bound sialic acid were determined by HPTLC
      densitometry with resorcinol as the coloring reagent. The total amounts of lipid
      bound sialic acid were 156.5 ng/mg of wet tissue in the Ist cranial nerve
      (olfactory tract) and 131.9 ng/mg in the IInd nerve, greater than the amounts in
      the other nerves (99.1-120.0 ng/mg). The Ist, IInd, and VIIIth nerves had GM4,
      but not LM1. It may reflect their histological feature of the central nervous
      system. The IIIrd, IVth, and VIth nerves, as well as the IInd, had significantly
      higher percentages of GQ1b (11.6-13.2%) than the other nerves (5.2-8.4%). The
      high proportion of GQ1b specific to these three cranial nerves involved in the
      ocular movement lends support to the role of serum anti-GQ1b antibody in the
      pathogenetic mechanisms of ophthalmoplegia in Miller Fisher syndrome and Guillain
      Barre syndrome.

PMID- 9037392
TI  - The effect of estradiol-induced hypothalamic pathology on sulfated glycoprotein-2
      (clusterin) expression in the hypothalamus.
AB  - Sulfated glycoprotein-2 (SGP-2 or clusterin) is a complex multifunctional
      molecule that has been recently been implicated in neuronal degeneration and
      remodeling. We have shown that estradiol treatment results in a selective
      destruction of beta-endorphin neurons in the hypothalamic arcuate nucleus. We
      have used immunocytochemistry to determine the distribution of SGP-2
      immunoreactivity in the rat hypothalamus and to assess the effects of the
      estradiol-induced destruction of beta-endorphin neurons on SGP-2 expression. We
      have found that SGP-2-immunopositive neurons normally occur in the medial
      preoptic area (MPOA), supraoptic nucleus (SON), paraventricular nucleus (PVN),
      dorsomedial nucleus (DM), and the lateral hypothalamic area (LHA) in both males
      and females. The neuropil appears free of label. Treatment with estradiol
      valerate results in the appearance of immunopositive punctate deposits in the
      neuropil in the MPOA, PVN and DM. The number and distribution of SGP-2-positive
      neurons are unaffected by estradiol treatment except in the MPOA, where there are
      twice as many SGP-2-positive neurons as in controls. These effects are precluded
      by treatment with vitamin E, with blocks the cytotoxic action of estradiol on
      beta-endorphin neurons. Thus, we interpret these changes as responses to the loss
      of beta-endorphin afferents.

PMID- 9037393
TI  - Activation of metabotropic glutamate receptors increases endogenous protein
      kinase C substrate phosphorylation in adult hippocampal slices.
AB  - We previously reported (Staak, S., Behnisch, T. and Angenstein, F., Hippocampal
      long-term potentiation: transient increase but no persistent translocation of
      protein kinase C (PKC) isoenzymes alpha and beta, Brain Res., 682 (1995) 55-62)
      that Ca(2+)-dependent PKC isoenzymes alpha/beta and gamma are not translocated
      between subcellular compartments after stimulation of glutamate receptor subtypes
      in hippocampal slices. Extending our previous work in this study in situ
      phosphorylation of endogenous PKC substrates and the translocation of novel PKC
      isoenzymes delta and epsilon was analysed to detect PKC activation. Two proteins
      of approximately 94 kDa and 18 kDa were first characterised to be specific PKC
      substrates. As control of the technique carbachol was shown to increase in situ
      phosphorylation of the two substrates without any measurable translocation of PKC
      protein. Activation of metabotropic glutamate receptors by 50 microM DHPG also
      increased the situ-phosphorylation by 43.9% (94 kDa) and 32.8% (18 kDa) compared
      to controls but did not induce a measurable subcellular redistribution of
      conventional and novel PKC isoenzymes. Stimulation by 50 microM trans-ACPD or 0.1
      mM quisqualate enhanced the situ phosphorylation in the same range, whereas 0.1
      mM NMDA was ineffective. To our knowledge this is the first report showing a
      direct link between metabotropic glutamate receptor activation and increased
      endogenous PKC substrate phosphorylation in adult hippocampal slices. This PKC
      activation was not detectable by a redistribution of enzyme protein between
      subcellular compartments. We, therefore, conclude, that the failure to detect PKC
      translocation in physiological experiments is not an indicator for unchanged
      enzyme activity.

PMID- 9037394
TI  - Whole-cell NMDA-evoked current in suprachiasmatic neurones of the rat: modulation
      by extracellular calcium ions.
AB  - The action of N-methyl-D-aspartic acid (NMDA) on suprachiasmatic neurones was
      studied using whole-cell recordings in coronal hypothalamic slices of the rat.
      The location of the recorded neurones within the suprachiasmatic nucleus was
      ascertained by intracellular labelling with biocytin, followed by histological
      processing of the slice. Suprachiasmatic neurones had an input resistance of 780
      +/- 20 M omega (mean +/- S.E.M.; n = 106). They were voltage-clamped at or near
      their resting membrane potential and their responsiveness to NMDA was tested by
      adding this compound to the perfusion solution. NMDA generated an inward current
      in about 85% of the neurones. At 50 microM, the average induced peak current was
      30 +/- 10 pA (n = 32); at 100 microM, it was 50 +/- 10 pA (n = 12). The NMDA
      induced current was reduced by D-2-amino-5-phosphopentanoic acid (D-AP5), and
      NMDA receptor antagonist, and was suppressed by MK-801, and NMDA channel blocker.
      Reducing the extracellular magnesium concentration from 1 to 0.01 mM caused a 2-
      to 3-fold increase in the amplitude of this current. Thus, suprachiasmatic
      neurones are endowed with functional NMDA receptor-channels, which may play a
      role in glutaminergic transmission in this nucleus. Decreasing the extracellular
      calcium concentration from 2 to 0.01 mM caused a 1.3- to 4.5-fold enhancement in
      the whole-cell NMDA current. This effect was probably not mediated by a change in
      the intracellular free calcium concentration. Indeed, loading suprachiasmatic
      neurones with 11 or 20 mM of the calcium chelator, 1,2-bis(2- aminophenoxy)ethane
      N,N,N',N'-tetracetic acid (BAPTA) suppressed a calcium-dependent slowly decaying
      outward aftercurrent but did not affect the low-calcium-induced facilitation of
      the NMDA response. NMDA current-voltage relations were established in normal and
      low-calcium perfusion solutions. In the normal solution, the net current
      generated by NMDA contained a region of negative slope conductance and reversed
      in polarity at 7 +/- 2 mV. In the low-calcium solution, this current increased in
      amplitude in the region of negative slope conductance, whereas at more
      depolarized potentials it was not altered. The NMDA-induced current was fitted
      using the Boltzmann equation. The effect of a low-calcium solution could be
      modelled by shifting the activation of the NMDA-sensitive conductance in the
      negative direction, by about 17 mV. We conjecture that lowering external calcium
      can unmask negative surface charges located on or near the NMDA channel and that
      this, in turn, weakens the voltage-dependent block of the channel by magnesium. A
      voltage-dependent blockade of the NMDA channel by calcium, however, may be also
      contribute to this effect. This low-calcium-induced facilitation of the NMDA
      response could play a regulatory role by enhancing calcium influx through the
      NMDA channel in case of calcium depletion in its vicinity.

PMID- 9037395
TI  - Subcellular localization of neuronal nitric oxide synthase in the brain of a
      teleost; an immunoelectron and confocal microscopical study.
AB  - The subcellular localization of neuronal nitric oxide (NO) synthase (NOS)
      immunoreactive (NOSir) elements in the brain of the Atlantic salmon was
      investigated by means of electron microscopy and confocal laser scanning
      microscopy. NOSir structures are present only in neuronal elements. In neuronal
      processes, strong NOS immunoreactivity was mainly localized within synaptic
      vesicles or seen as a dense accumulation associated with the plasma membrane of
      dendrites and at terminal formations. NOSir precipitate was also associated with
      microtubuli and mitochondrial outer membranes. The highest accumulation of NOS
      immunoreactivity was found in dendrites located in close apposition to
      immunonegative myelinated or unmyelinated neural processes. Several NOSir and
      unmyelinated immunonegative profiles formed synaptic specializations.
      Immunonegative neurons in contact with NOSir processes always contained round
      clear synaptic vesicles. In neuronal somata, strong NOS immunoreactivity was
      localized in the cristae of some large mitochondria, whereas vacuoles and the
      endoplasmic reticulum showed a relatively weak staining. Confocal microscopic
      analysis of NOS immunofluorescence showed a corresponding subcellular
      localization of NOS in different brain regions, but also indicated the presence
      of NOS axosomatic terminals. Our data show that specific neurons contain a
      neuronal NOS-like molecule which to a high degree is stored in vesicles and is
      accumulated at various sites along the neuronal processes or at specific synaptic
      terminal formations. Thus, NO may be formed and exert its action at various sites
      along the processes of NOS-synthesizing neurons. The present study provides
      evidence at the ultrastructural level that NO may play a messenger role in neural
      circuits involved in visual and hypophysiotrophic brain functions.

PMID- 9037397
TI  - Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain
      using [3H]WAY-100635 and [11C]way-100635.
AB  - The distribution of 5-HT1A receptors was examined in the post-mortem human brain
      using whole hemisphere autoradiography and the selective 5-HT1A receptor
      antagonist [3H]WAY-100635 ([O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1
      piperazinyl)ethyl)-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride). The
      autoradiograms showed very dense binding to hippocampus, raphe nuclei and
      neocortex. The labeling in neocortex was slightly lower than in the hippocampus
      and was mainly at superficial layers, although a faintly labeled band could be
      seen in deeper neocortical layers. Other regions, such as the amygdala, septum
      and claustrum, showed low densities caudatus and putamen, in cerebellum or in
      structures of the brain stem except in the raphe nuclei. The labeling of human 5
      HT1A receptors with [3H]WAY-100635 was antagonised by the addition of 5-HT1A
      receptor ligands, 5-HT, buspirone, pindolol or 8-OH-DPAT (10 microM), leaving a
      very low background of non-specific binding. Saturation analysis of
      semiquantitative data from several human regions indicated that [3H]WAY-100635
      has a Kd of approximately 2.5 nM. The selective labeling of 5-HT1A receptors with
      [3H]WAY-100635 clearly show that this compound is useful for further studies of
      the human 5-HT1a receptor subtype in vitro [11C]WAY-100635 is used for the
      characterization of 5-HT1A receptors with positron emission tomography (PET). WAY
      100635 was also radiolabeled with the short-lived positron-emitting radionuclide
      carbon-11 (t1/2 = 20 min) and used for in vitro autoradiography on human whole
      hemisphere cryosections. [11C]WAY-100635 gave images qualitatively similar to
      those of [3H]WAY-100635, although with a lower resolution. Thus, the hippocampal
      formation was densely labeled, with lower density in the neocortex. Buspirone,
      pindolol or 8-OH-DPAT (10 microM), blocked all binding of [11C]WAY-100635. The in
      vitro autoradiography of the distribution of 5-HT1A receptors obtained with
      radiolabeled WAY-100635 provide detailed qualitative and quantitative information
      on the distribution of 5-HT1A-receptors in the human brain. Moreover, the studies
      give reference information for the interpretation of previous initial results at
      much lower resolution in humans with PET and [11C]Way-100635. These data provide
      a strong basis for expecting [11C]WAY-100635 to behave as a highly selective
      radioligand in vivo.

PMID- 9037396
TI  - Contribution of sacral spinal cord neurons to the autonomic and somatic
      consequences of withdrawal from morphine in the rat.
AB  - In this study, we monitored Fos-like immunoreactivity in the sacral spinal cord
      to identify neurons that are likely to contribute to the autonomic manifestations
      of opioid antagonist-precipitated withdrawal in morphine-tolerant rats. Injection
      of systemic antagonist increased the Fos-like immunoreactivity throughout the
      first sacral segment, particularly in laminae I/II, X, and in the sacral
      parasympathetic nucleus (SPN). Selective peripheral withdrawal, with a
      hydrophilic antagonist that does not cross the blood-brain barrier (BBB), induced
      diarrhea, but no other withdrawal signs were evident. Compared to rats that
      withdrew systemically, peripherally withdrawal evoked significantly less Fos-like
      immunoreactivity in laminae V/VI, X and the SPN. By contrast, selective spinal
      withdrawal, by intrathecal injection of an opioid antagonist that does not cross
      the BBB, provoked hyperactivity of the hindlimbs and tail, but no diarrhea. These
      animals demonstrated significantly increased Fos-like immunoreactivity in laminae
      I/II, V/VI, the SPN, and the ventral horn compared to rats that withdrew
      systemically. Animals treated neonatally with capsaicin, to eliminate C-fiber
      input, demonstrated withdrawal behavior similar to intact withdrawing rats,
      except that the capsaicin-pretreated rats had significantly greater weight loss.
      However, this group had less Fos-like immunoreactivity in laminae V/VI, X and SPN
      compared to the intact withdrawing rats. These data suggest that withdrawal from
      morphine evokes hyperactivity of sacral neurons, particularly those involved in
      regions that process nociceptive and autonomic information. Peripheral withdrawal
      is sufficient to induce diarrhea, but it does not fully explain the associated
      weight loss. Unmyelinated primary afferents may contribute a tonic peripheral
      inhibition of circuits that regulate gut motility and intestinal fluid transport.
      Taken together, these data suggest that chronic exposure to opioids induces a
      latent sensitization in sacral cord neurons that can be manifested as neuronal
      hyperactivity during withdrawal; this mechanism may underlie withdrawal-induced
      hyperalgesia and gut hypermotility.

PMID- 9037398
TI  - The contribution of endogenous mono-ADP-ribosylation to kindling-induced
      epileptogenesis.
AB  - We examined the alteration of endogenous mono ADP-ribosylation in the hippocampus
      of amygdaloid kindled rats to clarify the neurochemical basis of epilepsy. A
      significant increase of the ADP-ribosylation on the 38 kDa protein was observed
      in the hippocampal membrane of the kindled rat. Several antiepileptics
      (phenytoin, phenobarbital, carbamazepine, sodium valproate) significantly
      decreased the ADP-ribosylation on the 38 kDa protein and effaced the increase in
      the kindled group. The ADP-ribosylation was largely increased by sodium
      nitroprusside, a nitric oxide generating compound, in both the kindled and
      control groups. Carbamazepine could not affect the ADP-ribosylation in the
      presence of sodium nitroprusside. Twenty amino acids from the N-terminus of the
      ADP-ribosylated 38 kDa protein were determined by sequential analysis. The
      sequence was completely identical to that of glyceraldehyde-3-phosphate
      dehydrogenase. These results indicate that the endogenous mono-ADP-ribosylation
      which increased in the kindled group and decreased by the antiepileptics might be
      a specific reaction associated with the mechanisms of epileptogenesis.

PMID- 9037399
TI  - Effects of NMDA-R1 antisense oligodeoxynucleotide administration: behavioral and
      radioligand binding studies.
AB  - The effects of an antisense phosphodiester oligodeoxynucleotide (ODN) directed to
      the NR1 subunit of the NMDA receptor mRNA and of its corresponding sense ODN were
      investigated in mice. Treatment with the antisense ODN significantly increased
      the time mice spent in the open arms of an elevated maze while the total number
      of arm entries was unaltered. Furthermore, seizure latencies after the
      administration of an ED100 dose of NMDA (150 mg/kg) were significantly higher in
      antisense treated animals compared to vehicle controls. At the same time,
      treatment with NR1 antisense ODN significantly reduced the Bmax of [3H]CGS-19755
      binding (2101 fmol/mg protein) compared to both vehicle (2787 fmol/mg protein)
      and sense (2832 +/- 39 fmol/mg protein) controls without any significant change
      in KD (33 nM). A corresponding reduction of [3H]CGP-39653 binding was also
      observed after treatment with NR1 antisense compared to both sense and vehicle
      controls. In contrast, neither antisense nor sense ODNs altered the proportion of
      high affinity glycine sites or the potency of glycine at either high or low
      affinity glycine binding sites to inhibit [3H]CGP-39653 binding. These results
      show that in vivo treatment with NR1 antisense ODNs to the NMDA receptor complex
      reduces antagonist binding at NMDA receptors and has pharmacological effects
      similar to those observed with some NMDA receptor antagonists. These results also
      suggest that treatment with antisense ODNs may provide another means to
      investigate allosteric modulation of receptor subtypes in vivo.

PMID- 9037400
TI  - Loss of hippocampal CA1 neurons and learning impairment in subicular lesioned
      rats.
AB  - 30-Day-old male Wistar rats were tested for acquisition and retention of operant
      conditioned behavior after bilateral subicular lesions made either
      electrolytically or chemically (ibotenic acid). The acquisition of operant
      learning was carried out in lesioned rats by assessing the number of sessions
      required to learn the operant task, whereas the retention test was performed
      after lesions by assessing performance on a previously learnt operant task. The
      acquisition of pedal press operant learning was significantly delayed in both
      types of lesioned rats, without any impairment in the retention of the previously
      learned task after lesioning. In these animals the cell densities were quantified
      in cresyl violet-stained sections in different subfields of hippocampus.
      Following the lesion of subiculum, selective degeneration of CA1 cells without
      the involvement of other hippocampal subfields was observed. This might be due to
      the loss of target area (subiculum) through which hippocampus is connected with
      neocortical and subcortical structures. This, in turn, might have resulted in
      behavioral deficits. The data suggest that the subiculum might be involved in the
      acquisition of new information rather than in retention.

PMID- 9037401
TI  - Flumazenil reverses the decrease in the hypnotic activity of pentobarbital by
      social isolation stress: are endogenous benzodiazepine receptor ligands involved?
AB  - Long-term social isolation stress has been shown to cause a decrease in
      pentobarbital (PB)-induced sleeping time in mice. In the present study, to
      clarify whether the GABAA/benzodiazepine (BZD) receptor system is involved in the
      decrease in the hypnotic activity of PB by social isolation stress, we examined
      the effects of BZD receptor ligands on the PB-induced sleep in group-housed and
      socially isolated mice. Moreover, we also tested whether social isolation stress
      affects the ability of GABA to stimulate 36Cl- uptake or the modulatory effect of
      diazepam and PB and GABA-induced stimulation of 36Cl- uptake into
      synaptoneurosomes prepared from mouse brain. Social isolation stress
      significantly decreased the PB-induced sleeping time in mice. The BZD receptor
      diazepam (0.1-0.8 mg/kg, i.p.) dose-dependently prolonged PB sleep in group
      housed and isolated mice, but the effect was weaker in isolated mice. In
      contrast, FG7142 (5-10 mg/kg, i.p.), a BZD receptor inverse agonist, shortened
      the sleep in group-housed but not in isolated mice. Flumazenil (16.5-33 nmol,
      i.c.v.), a selective BZD receptor antagonist, caused PB sleep in isolated mice to
      return to the level of group-housed mice, at the dose that antagonized the
      effects of diazepam and FG7142 on PB sleep in group-housed mice. However, this
      antagonist alone produced no effect on PB sleep in group-housed mice. Social
      isolation stress decreased the ability of GABA (0.6-200 microM) to stimulate 36Cl
      uptake into synaptoneurosomes but this stress had no effect on PB- and diazepam
      induced enhancement of GABA-stimulated 36Cl- uptake. These results suggest that
      endogenous substance(s) with an inverse BZD receptor agonist-like property and
      the changes in the ability of GABA to stimulate chloride ion channels are
      involved in the decrease in the hypnotic activity of pentobarbital following
      social isolation stress.

PMID- 9037402
TI  - Human auditory cortex is activated by omissions of auditory stimuli.
AB  - Cortical signals associated with infrequent tone omissions were recorded from 9
      healthy adults with a whole-head 122 channel neuromagnetometer. The stimulus
      sequence consisted of monaural (left or right) 50-ms 1-kHz tones repeated every
      0.2 or 0.5 s, with 7% of the tones randomly omitted. Tones elicited typical
      responses in the supratemporal auditory cortices. Omissions evoked strong
      responses over temporal and frontal areas, independently of the side of
      stimulation, with peak amplitudes at 145-195 ms. Response amplitudes were 60%
      weaker when the subject was not attending to the stimuli. Omission responses
      originated in supratemporal auditory cortices bilaterally, indicating that
      auditory cortex plays an important role in the brain's modelling of temporal
      characteristics of the auditory environment. Additional activity was observed in
      the posterolateral frontal cortex and in the superior temporal sulcus, more often
      in the right than in the left hemisphere.

PMID- 9037403
TI  - Corticosterone alters G protein alpha-subunit levels in the rat hippocampus.
AB  - The hypothalamic-pituitary-adrenal axis regulates the synthesis and secretion of
      corticosteroid hormones. The hippocampus, a component of the limbic system,
      contains the highest concentration of corticosteroid receptors in the brain and
      may play an important role in regulating hypothalamic-pituitary-adrenal axis
      activity and mediating physiological responses to stress. The corticosteroid
      hormone corticosterone alters the response elicited by activation of several
      different G protein-linked neurotransmitter receptors in the hippocampus. In the
      present study we used Western blot and immunohistochemical techniques to
      determine the effects of chronic adrenalectomy (ADX), low basal (CT) and high
      (HCT) corticosterone treatments on Gs, Gi1 and 2 and Go alpha-subunit levels and
      intracellular location in the rat hippocampus. CT treatment increased Gs alpha
      subunit levels and HCT treatment increased the levels of Gs, Gi1 and 2 and Go
      alpha-subunits when compared to sham as detected on Western blots. No change in
      the intracellular location of the G protein alpha-subunits was detected using
      immunohistochemistry. Based on our results, we conclude that corticosterone
      alters G protein alpha-subunit levels in the rat hippocampus without altering
      their intracellular location. These results provide an important piece of
      information towards understanding how corticosteroids alter G protein-linked
      neurotransmitter receptor-mediated responses.

PMID- 9037404
TI  - Interaction of cholecystokinin and somatostatin with a selective mu-opioid
      agonist and mu- and kappa-antagonists in thermoregulation.
AB  - We examined the effects of intracerebroventricular (i.c.v.) injections of
      cholecystokinin-octapeptide (CCK-8) and somatostatin (SST) and the interactions
      of these neuropeptides with the selective opioid antagonists, CTAP (mu) and nor
      BNI (kappa) and the mu-agonist, PL017, on body temperature (Tb) of the rat at
      normal ambient temperature (21 +/- 0.5 degrees C). CCK-8 produced short-lasting
      (15-60 min), dose-related increases in Tb in a dose range of 20 to 900 ng but did
      not change the Tb at lower doses (0.1-2 ng). Lower doses of SST (1 and 2
      micrograms) produced hyperthermia (30-60 min) and a higher dose of SST (10
      micrograms) caused hypothermia (30-45 min). PL017 (1 microgram, i.c.v.), alone
      and in combination with CCK-8, produced hyperthermia. The CCK-8 (300 ng)-induced
      hyperthermia was blocked by pretreatment of rats with CTAP (1 microgram, i.c.v.),
      suggesting that the higher doses of CCK-8 increase Tb through the interaction
      with mu-receptors or the enhancement of release of endogenous opioids acting on
      the mu-receptor. The hyperthermia elicited by a lower dose of SST (1 microgram)
      was prevented by pretreatment with CTAP but not with nor-BNI (1 microgram,
      i.c.v.). Pretreatment with nor-BNI blocked the higher dose (10 micrograms) of SST
      induced hypothermia. PL017 or CTAP did not prevent the hypothermic effect of that
      dose of SST. These results indicate that a lower dose of SST (1 microgram)
      stimulates the mu-receptor (directly or indirectly) and a higher dose (10
      micrograms) interacts with the kappa-receptor in regulation of Tb. Thus, the
      effects of both CCK-8 and SST on Tb appear to involve the endogenous opioid
      system.

PMID- 9037405
TI  - Rats with decreased brain cholecystokinin levels show increased responsiveness to
      peripheral electrical stimulation-induced analgesia.
AB  - Using the P77PMC strain of rat, which is genetically prone to audiogenic
      seizures, and also has decreased levels of cholecystokinin (CCK), we examined the
      analgesic response to peripheral electrical stimulation, which is, in part,
      opiate-mediated. A number of studies have suggested that CCK may function as an
      antagonist to endogenous opiate effects. Therefore, we hypothesized that the
      P77PMC animals would show an enhanced analgesic response based on their decreased
      CCK levels producing a diminished endogenous opiate antagonism. We found that the
      analgesic effect on tail flick latency produced by 100 Hz peripheral electrical
      stimulation was more potent and longer lasting in P77PMC rats than in control
      rats. Moreover, the potency of the stimulation-produced analgesia correlated with
      the vulnerability to audiogenic seizures in these rats. We were able to block the
      peripheral electrical stimulation-induced analgesia (PSIA) using a
      cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay
      showed that the content of CCK-8 in cerebral cortex, hippocampus and
      periaqueductal gray was much lower in P77PMC rat than in controls. These results
      suggest that low CCK-8 content in the central nervous system of the P77PMC rats
      may be related to the high analgesic response to peripheral electrical
      stimulation, and further support the notion that CCK may be endogenous opiate
      antagonist.

PMID- 9037406
TI  - Granule cell disinhibition in dentate gyrus of genetically seizure susceptible El
      mice.
AB  - Paired-pulse inhibition was investigated electrophysiologically in the dentate
      gyrus using hippocampal slices from epileptic El mice. At short interpulse
      intervals (IPIs), the inhibition was 30% in the El, and 90% in the control ddY
      mice at the ages of 10 and 15 weeks. No difference in inhibition was observed at
      the age of 5 weeks. Bicuculline, a GABAA receptor antagonists, attenuated the
      inhibition during short IPIs n the ddY mice, while in the El mice, phenobarbital
      and flunitrazepam, which enhance GABAA receptor function, restored the inhibitory
      activity comparable to that of the ddY. The disinhibition progressed with growth,
      closely correlating with seizure development in El mice. These results suggest
      that decrease in the GABAergic inhibition occurs in the dentate gyrus of the El
      mice with growth. GABA concentration in the hippocampus was also quantified using
      HPLC. In El mice, GABA level was significantly lower than that in ddY mice at the
      ages of 5 and 15 weeks. Thus, the disinhibition observed in the El dentate gyrus
      at 15 weeks of age does not appear to be directly related to the content of GABA.
      GABAergic disinhibition suggests possible loss of unknown inhibition control
      factor(s) in the El dentate gyrus as growth progresses. The growth-dependent
      disinhibition in the granule cells may be prerequisite for epileptogenesis in El
      mice.

PMID- 9037407
TI  - Effect of morphine on striatal dopamine metabolism and ascorbic and uric acid
      release in freely moving rats.
AB  - Recent ex vivo findings have shown that morphine increases dopamine (DA) and
      xanthine oxidative metabolism and ascorbic acid (AA) oxidation in the rat
      striatum. In the present study, we evaluated the effects of subcutaneous daily
      morphine (20 mg/kg) administration on DA, dihydroxyphenylacetic acid (DOPAC),
      homovanillic acid (HVA), AA and uric acid in the striatum of freely moving rats
      using microdialysis. Dialysates were assayed by high performance liquid
      chromatography with electrochemical detection. On the first day, morphine
      administration caused a significant increase in extracellular DA, DOPAC, HVA, AA
      and uric acid concentrations over a 3 h period after morphine. In all treated
      rats (n = 7), individual concentrations of DOPAC + HVA were directly correlated
      with individual AA and uric acid concentrations. Last morphine administration on
      the 4th day increased DOPAC, HVA, AA and uric acid concentrations but failed to
      increase those of DA. Individual DOPAC + HVA concentrations were still directly
      correlated with individual AA and uric acid concentrations. These results suggest
      that systemic morphine increases both striatal DA release and DA and xanthine
      oxidative metabolism. Only the former effect undergoes tolerance. The increase in
      DA oxidative metabolism is highly correlated with that of xanthine. The
      subsequent enhancement in reactive oxygen species production may account for the
      increase in extracellular AA.

PMID- 9037408
TI  - Harmaline-induced tremor and impairment of learning are both blocked by
      dizocilpine in the rabbit.
AB  - Harmaline is known to produce tremors and retard acquisition of the rabbit's
      nictitating membrane response. These actions have been demonstrated to depend on
      the ability of harmaline to activate the inferior olive which gives rise to
      climbing fibers that project directly onto Purkinje cells in cerebellar cortex.
      However, the precise receptor systems involved in harmaline's actions remains
      unknown. This study examined the role of the NMDA receptor in harmaline's
      actions. Harmaline (10 mg/kg, s.c.) produced intense tremors and impaired the
      acquisition of conditioned responses. Both of these effects of harmaline were
      significantly blocked by the prior administration of the noncompetitive NMDA
      channel blocker, dizocilpine (0.01 mg/kg, s.c. given 20 min prior to the
      administration of harmaline). This dose od dizocilpine had no effect on
      acquisition of conditioned responses when given alone. A higher dose of
      dizocilpine (0.1 mg/kg s.c.) completely blocked the tremorogenic effects of
      harmaline (10 mg/kg, s.c.). Dizocilpine had no effect on motor behavior when
      given alone. It was suggested that the blockade of harmaline's actions by
      dizocilpine may be occurring at NMDA channels within the inferior olive.
      Regardless of the site of action, these data demonstrate that harmaline's ability
      to activate the interior olivary nucleus depends on the normal activity of the
      NMDA receptor.

PMID- 9037409
TI  - Membrane and synaptic properties of mitral cells in slices of rat olfactory bulb.
AB  - We have investigated the membrane properties and excitatory synaptic transmission
      of mitral cells in a slice preparation of rat olfactory bulb. In response to
      intracellular injection of depolarizing current, most mitral cells showed several
      distinct membrane properties: (1) delayed onset of firing (suggesting the
      presence of a type of potassium A current); (2) subthreshold oscillation of the
      membrane potential; and (3) repetitive firing of clustered action potentials
      during prolonged threshold stimulation. Olfactory nerve (ON) stimulation evoked a
      long-lasting EPSP in most of the mitral cells. This long EPSP was completely
      blocked by combined application of NMDA and non-NMDA receptor antagonists (20
      microM CNQX and 100 microM APV), confirming that glutamate is the
      neurotransmitter at the synapses from ON to mitral cells. The ON-evoked EPSP was
      preceded by a prespike, which was resistant to membrane potential
      hyperpolarization at the soma. This fast prepotential may be indicative of an
      active response in the primary dendritic tufts of the mitral cells. Stimulation
      of the lateral olfactory tract evoked an antidromic pulse followed by a short
      EPSP, which could also be elicited independently of an antidromic spike in the
      recorded cell. Since the asymmetrical synapses so far observed on the mitral
      cells are all form the ON, this antidromically evoked EPSP may reflect self
      excitation of a mitral cell by glutamate released from its own dendrites by
      antidromic impulse invasion, or/and lateral excitation by neighboring invaded
      dendrites.

PMID- 9037410
TI  - Anterograde tracing of retinohypothalamic afferents with Fluoro-Gold.
AB  - The anterograde neuronal tracing properties of Fluoro-Gold (FG) were
      characterized in this study by its ability to label the retinohypothalamic tract
      (RHT) upon pressure injection of the substance into the vitrous body of the eye
      in the Djungarian hamster, Phodopus sungorus. Tracing was compared to the
      anterograde neuronal transport of cholera toxin B subunit (CTB), Fast blue (FB),
      Phaseolous vulgaris leucoagglutinin (PHA-L) and biocytin. After survival times
      that ranged from 24 h to 4 weeks, a major projection was found to the bilateral
      hypothalamic suprachiasmatic nuclei (SCN). Labeling was also found in the
      anterior medial preoptic nucleus and, in relatively sparse amounts, in the
      lateral geniculate nucleus, superior colliculus and lateral habenular nucleus.
      Similar results were obtained upon injection of CTB or FB, respectively, into the
      eye, whereas the application of PHA-L or biocytin did not label retinal
      afferents. The combined injection of FG and CTB or FB into the same eye labeled
      retino-afferent fibers only when FG was applied three days before the injection
      of the other tracers. Retrogradely labelled neurons were sen occasionally in the
      hypothalamus which may provide a sparse retinopetal projection. Additional
      experiments combining FG tracing and the immunofluorescent detection of the
      neuropeptides substance P (SP) or vasoactive intestinal polypeptide (VIP) in the
      SCN showed that FG-containing punctae were accumulated in the vicinity of
      immunoreactive cell bodies. Our data demonstrate that FG may be used as an
      anterograde axonal tracer of the retinohypothalamic pathway.

PMID- 9037411
TI  - Comparisons of the effects of enterostatin on food intake and gastric emptying in
      rats.
AB  - The effects of central and peripheral administration of enterostatin (ENT) on
      food intake and gastric emptying of a non-nutrient liquid meal have been studied
      in rats. Intraperitoneal and intragastric administration of ENT at a dose of 120
      nmol suppressed the intake of a high-fat diet but failed to inhibit gastric
      emptying in Sprague-Dawley (SD) rats. Intracerebroventricular (i.c.v.) ENT (1
      nmol) reduced intake of a high-fate diet in Osborne-Mendel (OM) and SD rats but
      not in S5B/Pl rats, whereas it decreased gastric emptying in S5B/P1 and SD rats
      but not in OM rats. The data suggest that although central ENT may reduce gastric
      emptying rate, this effect is not related to the inhibitory effect of ENT on food
      intake.

PMID- 9037412
TI  - Altered Na(+)-channel function as an in vitro model of the ischemic penumbra:
      action of lubeluzole and other neuroprotective drugs.
AB  - Veratridine blocks Na(+)-channel inactivation and causes a persistant Na(+)
      influx. Exposure of hippocampal slices to 10 microM veratridine led to a failure
      of synaptic transmission, repetitive spreading depression (SD)-like
      depolarizations of increasing duration, loss of Ca(+)-homeostasis, a large
      reduction of membrane potential, spongious edema and metabolic failure.
      Normalization of the amplitude of the negative DC shift evoked by high K+ ACSF 80
      min after veratridine exposure was taken as the primary endpoint for
      neuroprotection. Compounds whose mechanisms of action includes Na(+)-channel
      modulation were neuroprotective (IC50-values in microM): tetrodotoxin 0.017,
      verapamil 1.18, riluzole 1.95, lamotrigine > or = 10, and diphenylhydantoin 16.1.
      Both NMDA (MK-801 and PH) and non-NMDA (NBQX) excitatory amino acid antagonists
      were inactive, as were NOS-synthesis inhibitor (nitro-L-arginine and L-NAME)
      Ca(2+)-channel blockers (cadmium, nimodipine) and a K(+)-channel blocker (TEA).
      Lubeluzole significantly delayed in time before the slices became epileptic,
      postponed the first SD-like depolarization, allowed the slices to better recover
      their membrane potential after a larger number of SD-like DC depolarizations,
      preserved Ca2+ and energy homeostasis, and prevented the neurotoxic effects of
      veratridine (IC50-value 0.54 microM). A concentration of lubeluzole, which was 40
      x higher than its IC50-value for neuroprotection against veratridine, had no
      effect on repetitive Na(+)-dependent action potentials induced by depolarizing
      current in normal ACSF. The ability of lubeluzole to prevent the pathological
      consequences of excessive Na(+)-influx, without altering normal Na(+)- channel
      function may be of benefit in stroke.

PMID- 9037413
TI  - Implication of protein kinase C in mechanisms of potassium-induced long-term
      potentiation in rat hippocampal slices.
AB  - The involvement of Ca2+/phospholipid-dependent (alpha, beta, gamma, PKCs) and
      Ca(2+)-independent PKC (epsilon and zeta isoforms) in mechanisms of long-term
      potentiation was investigated in CA1 hippocampal slices, using a brief high
      potassium pulse (50 mM, 40 s) to induce long-term potentiation (K+/LTP). The K+
      pulse induced first, in 15 s a translocation of PKC activity to the membrane.
      This was rapidly followed, from 1 to 60 min after the pulse, by a selective
      activation of PKC in the cytosol. This activation, which could be blocked by the
      NMDA (N-methyl-D-aspartate) receptor antagonist 2-amino-5-phosphonovalerate
      (APV), was associated with a significant increase n immunoreactivity for gamma
      PKC in he cytosol, and also to a less degree for beta PKC. In contrast,
      application of the phorbol ester PMA (phorbol 12-mirystate 13 acetate) to other
      slices induced a rapid and persistent translocation to the membrane of alpha,
      beta, epsilon and zeta PKCs. A major role for the activation role for the
      activation of cytosolic gamma PKC in the maintenance of LTP is discussed.

PMID- 9037414
TI  - Altered intracellular localization of the glutamate receptor channel delta 2
      subunit in weaver and reeler Purkinje cells.
AB  - The glutamate receptor (GluR) channel delta 2 subunit is expressed abundantly and
      specifically in cerebellar Purkinje cells. Our previous study demonstrated that
      the GluR is expressed as early as embryonic day 15 prior to Purkinje cell
      synaptogenesis, and its protein product accumulates in dendritic spines during
      normal Purkinje cell maturation. In this study, we examined expression and
      distribution of the GluR delta 2 in the weaver and reeler mutant cerebelli, which
      show abnormal cytoarchitecture and neural circuitry. In situ hybridization
      analysis showed that GluR delta 2 mRNA was expressed in entire Purkinje cells in
      both mutant mice. Immunohistochemical analysis revealed that intracellular
      localization of GluR delta 2 was altered in some region of mutant cerebelli. In
      the cortical surface where Purkinje cells from synapses with parallel fibers,
      GluR delta 2-immunoreactivity was restricted to dendritic spines of Purkinje
      cells as observed in normal mice. In contrast, in the subcortical region where
      granule cells and parallel fibers are absent, the immunoreactivity was found
      widely in Purkinje dendrites. Thus, the GluR delta 2 protein did not accumulate
      to the dendritic spines of Purkinje cells lacking synaptic contact with parallel
      fibers. These results suggest that the expression of both GluR delta 2 mRNA and
      protein is independent of abnormalities in the mutant cerebelli, but
      relocalization of the GluR delta 2 protein might depend on the formation of
      synapses between Purkinje cells and parallel fibers.

PMID- 9037415
TI  - Effects of multiple intracerebroventricular injections of [D-Pen2,D
      Pen5]enkephalin and [D-Ala2,Glu4]deltorphin II on tolerance to their analgesic
      action and on brain delta-opioid receptors.
AB  - Male Swiss-Webster mice were injected intracerebroventricularly (i.c.v.) with [D
      Pen2,D-Pen5]enkephalin (DPDPE), a delta 1-opioid receptor agonist (20 micrograms
      per mouse) twice a day for either 2 or 4 days. Vehicle injected mice served as
      controls. Treatment of mice with DPDPE for 2 or 4 days decreased its analgesic
      response by 44 and 76%, respectively in comparison to vehicle injected mice.
      Treatment of mice with DPDPE for 2 or 4 days decreased density (Bmax) of
      [3H]DPDPE to bind to brain homogenates by 77 and 76%, respectively, in comparison
      to vehicle injected controls but the apparent dissociation constant (kd) values
      were not altered. The effects of i.c.v. injections of [D-Ala2,Glu4]deltorphin II
      (deltorphin II), a delta 2-opioid receptor agonist (20 micrograms per mouse)
      twice a day for either 2 or 4 days on its analgesic response as well as on brain
      receptors for [3H]DPDPE were also determined. The analgesic response to
      deltorphin II decreased by 51 and 78%, respectively in mice treated with
      deltorphin II for 2 or 4 days, respectively. Two or four days treatment with
      deltorphin II decreased the Bmax of [3H]DPDPE by 76 and 87%, respectively. The 2
      day treatment also increased the Kd value by 58%, but the 4-day treatment with
      deltorphin II had no effect on the Kd of [3H]DPDPE to bind to brain membranes.
      Thus, multiple injections of delta 1- or delta 2-opioid receptor agonists results
      in the development of tolerance to their analgesic action and the intensity of
      tolerance increases with the duration of treatment. Both delta 1- and delta 2
      opioid receptor agonist, on chronic administration, result in the down-regulation
      of delta 1-opioid receptors labeled with [3H]DPDPE.

PMID- 9037416
TI  - Amygdala-kindled seizures increase the expression of corticotropin-releasing
      factor (CRF) and CRF-binding protein in GABAergic interneurons of the dentate
      hilus.
AB  - Kindling, a model of temporal lobe epilepsy, induces a number of neuropeptides
      including corticotropin-releasing factor (CRF). CRF itself can produce limbic
      seizures which resemble kindling in some aspects. However, tolerance to the
      convulsant effects of CRF develops rapidly. Hypothetically, this could be
      explained should seizures also induce the CRF-binding protein (CRF-BP), which has
      been postulated to restrict the actions of CRF. Therefore, in the present study,
      we used in situ hybridization to examine the effects of amygdala-kindled seizures
      on the mRNA levels of CRF and CRF-BP. Kindled seizures markedly elevated CRF and
      CRF-BP in the dentate gyrus of rats. CRF and CRF-BP were induced almost
      exclusively in GABAergic interneurons of the dentate hilus. The CRF and CRF-BP
      interneurons also expressed neuropeptide Y but not cholecystokinin. CRF appeared
      to have an excitatory role in the dentate gyrus as it decreased the
      afterhyperpolarization of dentate granule neurons. These results suggest that CRF
      may contribute to the development of amygdala kindling. However, the compensatory
      induction of CRF-BP may serve to limit the excitatory effects of CRF in the
      dentate gyrus.

PMID- 9037417
TI  - Brainstem-mediated locomotion and myoclonic jerks. I. Neural substrates.
AB  - Eleven of 40 decerebrated cats were found to exhibit periods of spontaneous or
      sensory myoclonus and locomotion beginning 24 h after decerebration. Histological
      analysis showed that the cats generating myoclonus hemorrhagic lesions in the
      retrorubral nucleus (RRN) and ventral mesopontine junction (vMPJ). However, with
      intact RRN and vMPJ never showed myoclonus. To verify that the lesions were
      responsible for myoclonus, 6 additional cats received N-methyl-D-aspartate (NMDA,
      0.5 M/0.5 microliter) injections in the areas of RRN and vMPJ to produce
      bilateral lesions. Coordinated rhythmic leg movement (locomotion) or myoclonic
      twitches developed in all of these cats beginning 3 hours after NMDA injection.
      These NMDA lesion-induced movements appeared either spontaneously (5 out of 6
      cats) or after sensory stimulation (1 cat). Four cats received saline control
      injections in the RRN and vMPJ and did not have spontaneous, or sensory
      stimulation-induced, myoclonic twitches during the 48 h observation period. These
      results indicate that the RRN and vMPJ have a suppressive effect on myoclonic
      twitches and rhythmic leg movement. Dysfunction of these regions could release
      motor activity into sleep and waking states.

PMID- 9037418
TI  - Brainstem-mediated locomotion and myoclonic jerks. II Pharmacological effects.
AB  - Previous studies in our laboratory have demonstrated that microinjection of N
      methyl-D-aspartate (NMDA) agonist into the nucleus magnocellularis (NMC) of the
      medial medulla increases muscle tone and/or produces locomotion, while injection
      of corticotropin-releasing factor (CRF) and non-NMDA agonists into the same or
      nearby sites suppresses muscle tone. In the first paper of this series, we report
      that myoclonic twitches or coordinated rhythmic leg movement (locomotion) can be
      induced by either NMDA or hemorrhagic bilateral lesion of the ventral mesopontine
      junction (vMPJ). In this paper, we report that microinjection of CRF (10 nM) or
      non-NMDA agonists, kainic acid (0.1-0.2 mM) and quisqualic acid (1-10 mM), into
      the NMC block locomotion and myoclonic twitches. The latency and duration of CRF
      and non-NMDA agonist-induced blockade of motor activity were short, at 34 s and
      3.6 min, respectively. However, microinjection of the NMDA agonists DL-2-amino-5
      phosphonovaleric acid (APV; 50 mM) or DL-2-amino-5-phosphonopentanoic acid (AP5,
      20 mM) block myoclonus at a latency of 0.6-3 min with the block lasting for a
      mean of 7 h. Thus, activation of non-NMDA receptors or inactivation of NMDA
      receptors in NMC can block myoclonus. An imbalance between the inputs to these
      receptor systems may contribute to the generation of abnormal motor activation in
      waking and sleep.

PMID- 9037419
TI  - Instrumental conditioning of the activity of putative command neurons in the
      mollusk Helix.
AB  - Gaining insight into the mechanism of generation of goal-directed actions is
      understanding neural function. In this study we examined the role of the action
      potential (AP) in a single molluscan neuron (responsible for a defensive
      response) in an instrumental behavior. The intracellular electrical activity of
      two neurons was recorded simultaneously. One neuron was trained and the other
      served as a control neuron. When the trained neuron produced an AP in response to
      a conditioned stimulus (CS), the mollusc did not receive a painful stimulus.
      Delivery of the painful stimulus did not depend on the response of the control
      neuron. The number of AP's in a trained neuron, the AP latency and the threshold
      revealed a bell-shaped dependence on learning, whereas the response of the
      control neuron to a CS decreased during learning. It is apparently feasible to
      elaborate this type of instrumental reflex, so that the discharge of a single
      neuron may serve as an instrumental action for the entire animal. The membrane
      potential in a trained neuron varies significantly during instrumental learning,
      but the change do not correspond to the dynamics of the instrumental reaction in
      the response to a CS. The control neuron exhibited weak but significant
      hyperpolarization during learning. The onset of the EPSP is determined by the
      timing of AP generation in presynaptic neurons. However, it changed in the
      trained neuron the elaboration of a instrumental reflex. The alterations in the
      latency of EPSP's during learning were significant, but were not consistent with
      the time history of the conditioned response. Therefore, although the learning
      procedure was directed to only one neuron, the presynaptic neurons and neurons at
      the same neuronal level (command-like neurons of the same behavior) participated
      in the learning. The sign of the participation was not necessarily the same as
      that in the trained neuron.

PMID- 9037420
TI  - Characterization of the K+ current mediated by 5-HT1A receptor in the acutely
      dissociated rat dorsal raphe neurons.
AB  - The action of 5-hydroxytryptamine (5-HT) via the 5-HT1A receptor on dissociated
      rat dorsal raphe neurons was characterized under the whole-cell mode by using the
      nystatin-perforated patch-clamp technique. Under voltage-clamp conditions, 5-HT
      induced an inwardly rectifying K+ current (I5-HT) in a concentration-dependent
      manner. I5-HT was mimicked by 8-OH-DPAT and buspirone, which are both 5-HT1A
      receptor agonists. I5-HT was reversibly blocked by such 5-HT1A receptor
      antagonists as (S)-UH-301 a 5-HT4 receptor antagonist. I5-HT was antagonized
      concentration-dependently by such K+ channel blockers as quinine, Ba2+ and 4
      aminopyridine but was relatively insensitive to both CS+ and tetraethylammonium.
      When the neurons were loaded with guanosine 5'-O-3-thiotriphosphate through a
      patch pipette, the K+ current induced by 5-HT became irreversible. N
      ethylmaleimide (NEM), a sulfhydryl alkylating agent, irreversibly blocked I5-HT.
      The intracellular perfusion with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid (BAPTA), a Ca2+ chelator, or neomycine, a phospholipase C
      inhibitor, never significantly affected the 5-HT-induced response. 12-Myristate
      13-acetate diester (PMA), a protein kinase C (PKC) activator, had only a weak
      inhibitory effect on I5-HT, and staurosporine, a PKC inhibitor, failed to
      significantly occlude I5-HT. Therefore, the K+ conductance activated via the 5
      HT1a receptor of dorsal raphe neurons was thus characterized by the sensitivity
      to such K+ channel blockers as quinine, Ba2+ and 4-aminopyridine. Moreover, G
      protein which is NEM-sensitive and can couple to the 5-HT1A receptor, is thus
      considered to activate the inwardly rectifying K+ conductance without being
      mediated by such second messengers as Ca2+ and PKC.

PMID- 9037422
TI  - 4-aminopyridine and l-cis-diltiazem block the cGMP-activated K+ channels closed
      by light in the molluscan extra-ocular photoreceptors.
AB  - The cGMP-activated K+ channels closed by light lead to the depolarizing
      photocurrent of photoreceptors in the Onchidium ganglion. Whole-cell current
      records showed that external application of 100-200 microM 4-aminopyridine or 200
      400 microM l-cis-diltiazem completely blocked the macroscopic photocurrent at any
      depolarizing and hyperpolarizing potentials. Single-channel current recordings
      suggested that both 4-aminopyridine and l-cis-diltiazem act to block the cGMP
      activated K+ channels in their open state from inside the cell.

PMID- 9037421
TI  - Calcium-binding proteins in the periglomerular region of typical and typical
      olfactory glomeruli.
AB  - The distribution of chemically identified neuronal populations was studied in the
      glomerular layer of the rat olfactory bulb using calcium-binding protein
      immunocytochemistry combined with acetylcholinesterase histochemistry. Four
      calcium-binding proteins (calbindin D-28k, parvalbumin, calretinin, and
      neurocalcin) were analyzed in the periglomerular region of two different
      glomerular subsets; typical and atypical glomeruli. Atypical glomeruli were
      clearly distinguishable from typical ones by their dense network of
      acetylcholinesterase-positive centrifugal fibers. Each calcium-binding protein
      studied showed a specific distribution pattern in the rat olfactory bulb.
      Calbindin D-28k-, calretinin-, and neurocalcin-immunoreactive neurons were
      specially abundant in the glomerular layer. These three calcium-binding proteins
      had their main expressions in neuronal subpopulations directly involved in the
      glomerular circuitries of the rat olfactory bulb. Specific populations of
      periglomerular cells were stained for calbindin D-28k, parvalbumin, calretinin,
      or neurocalcin, whereas external tufted cells were only immunoreactive to
      neurocalcin. Both neuronal types, periglomerular cells and external tufted cells,
      were found in the periglomerular region of both glomerular subsets. Nevertheless,
      a homogeneous distribution of calbindin D-28k- or calretinin-immunopositive
      periglomerular cells were found between typical and atypical glomeruli, whereas
      the neurocalcin-immunostained external tufted cells were statistically more
      abundant in typical glomeruli than atypical ones (P < 0.001). These data suggest
      that some neuronal subpopulations are related with general properties of the
      glomerular physiology, and they have a homogeneous distribution in different
      subsets of glomeruli, whereas other chemically identified populations are related
      with a finer tuning of the olfactory processing, and they are segregately
      distributed in relation to particular glomerular subsets. In addition, this work
      adds new differences in the cellular composition of typical and atypical
      glomeruli.

PMID- 9037423
TI  - Power spectral analysis of inspiratory nerve activity in the anesthetized rat:
      uncorrelated fast oscillations in different inspiratory nerves.
AB  - The spectral composition of the inspiratory nerve discharge was studied in
      spontaneously breathing Sprague-Dawley rats under urethane (n = 7) or barbiturate
      (n = 10). Left phrenic nerve activity was recorded simultaneously with right
      phrenic or left recurrent laryngeal nerves. We found that all neurograms showed
      prominent fast oscillators at common frequencies in the high frequency (HFO)
      range. Concurrent medium frequency oscillations (MFO) were present in inspiratory
      nerve discharges of four rats anesthetized with Nembutal. Significant coherences
      between nerves were uncommon (n = 2) and were only found between HFOs. Thus
      although nerve autospectra were dominated by HFO, weak correlations indicated a
      relatively weak system HFO in th central pattern generator, in the anesthetized
      rat.

PMID- 9037424
TI  - Acute hypertension increases norepinephrine release in the diagonal band of
      Broca.
AB  - In vivo microdialysis was used to measure extracellular concentrations of
      norepinephrine in the diagonal band of Broca (DBB) during changes in blood
      pressure in conscious rats. Dialysate norepinephrine concentration was
      significantly increased during acute hypertension (280 +/- 40% of control), but
      was not changed by hypotensive hemorrhage. These results are consistent with the
      proposal that noradrenergic innervation of the DBB is selectively activated by
      increased blood pressure.

PMID- 9037425
TI  - Intra-septal infusions of glucose potentiate inhibitory avoidance deficits when
      co-infused with the GABA agonist muscimol.
AB  - This experiment examined the effects of co-infusions of glucose with the gamma
      aminobutyric acid (GABA) agonist muscimol into the medial septum on memory for
      inhibitory avoidance learning. Co-infusions of muscimol (3 nmol) and glucose (33
      nmol) impaired memory, but neither drug did so when administered alone. Thus,
      although glucose typically reverses memory deficits, these results indicate that
      glucose potentiates the memory-impairing effects of a GABA agonist.

PMID- 9037426
TI  - Parabrachial nucleus neurons providing axons to both the thalamus and the spinal
      cord in the rat.
AB  - After injecting Fluoro-gold (FG) and tetramethylrhodamine-dextran amine (TMR-DA),
      respectively, into the medial part of the ventrobasal thalamus and the upper
      segments of the cervical cord of the rat, a small number of neuronal cell bodies
      were double-labeled retrogradely with both FG and TMR-DA in the parabrachial
      nuclear complex (BPN) ipsilateral to the injection into the thalamus. The cell
      bodies double-labeled with FG/TMR-DA were seen mainly in the Kolliker-Fuse
      subnucleus and additionally in the external medial subnucleus.

PMID- 9037427
TI  - Effect of seizures and diuretics on the osmolality of the cerebrospinal fluid.
AB  - There was a significant increase in the osmolality of the cerebrospinal fluid
      (CSF) of the anesthetized rats after treatment with 80 mg/kg (but not 39 mg/kg)
      furosemide and 1 g/kg of mannitol, but not during seizures induced by kainic
      acid. Furosemide (10 mg/kg) blocked seizure activity by kainic acid, while
      mannitol (1 g/kg) did not. The results suggest that the antiepileptic effect of
      furosemide is due to a direct CNS effect not related to a change in CSF
      osmolality.

PMID- 9037428
TI  - Low-dose amphetamine elevates movement-related firing of rat striatal neurons.
AB  - To study the striatal role in amphetamine's stimulant effects on motor behavior,
      single neurons were recorded in the dorsolateral striatum of unrestrained rats
      before and after amphetamine injection (0.5 or 1.0 mg/kg, i.p.). Comparisons of
      firing were made between similar motor behaviors before and after injection. Mean
      locomotor firing rates increased 5% to 276% within 30 min after injection and
      reversed within 2 h. Firing related to specific head- or forelimb-movements,
      which were similar in all measured parameters before and after injection, was
      elevated several hundred percent after injection and then reversed, the time
      course paralleling that of the stimulant effect on these movements. Elevation of
      movement-related striatal firing rates by low doses of the psychomotor stimulant
      is in line with established increases in firing rate normally observed for
      striatal neurons related to motor behavior.

PMID- 9037429
TI  - Dextrorphan, but not dextromethorphan, exerts weak antidystonic effects in mutant
      dystonic hamsters.
AB  - The effects of dextromethorphan and its metabolite dextrorphan on severity of
      dystonia were examined in mutant dystonic hamsters, an animal model of idiopathic
      paroxysmal dystonia, in which recent examinations have shown antidystonic effects
      of selective N-methyl-D-aspartate (NMDA) receptor antagonists. Dextromethorphan
      and dextrorphan are non-competitive NMDA receptor antagonists which additionally
      exhibit affinity for sigma receptors. Dextrorphan (20 and 40 mg/kg i.p.)
      significantly retarded the progression of dystonia at the higher dose, whereas
      dextromethorphan (20, 40, 60 mg/kg i.p.) failed to exert any antidystonic effects
      even at high doses which caused severe effects. The lack of antidystonic efficacy
      of dextromethorphan may be related to its higher affinity to sigma receptors
      compared with dextrorphan.

PMID- 9037430
TI  - Calcium channel types mediating synaptic transmission during aging.
AB  - The effects of omega-conotoxin (CTX) GVIA, omega-agatoxin (Aga) IVA, and the
      dihydropyridine nicardipine were studied on synaptic transmission in the
      hippocampus during aging. Field excitatory postsynaptic potentials (fEPSPs) were
      recorded in the CA1 region in slices from young and aged Fischer 344 rats.
      Peptide toxins reduced synaptic transmissions similarly in both age groups while
      nicardipine showed no effect. These results suggests that the well documented age
      related changes in synaptic transmissions in the hippocampus cannot be explained
      by changes in the types of Ca2+ channel mediating synaptic transmission.

PMID- 9037431
TI  - Apoptosis in the striatum of rats following intraperitoneal injection of 3
      nitropropionic acid.
AB  - The present study investigated the mechanism of cellular degeneration within the
      striatum following administration of the mitochondrial toxin, 3-nitropropionic (3
      NP) acid. Internucleosomal fragmentation typical of apoptosis was present in the
      DNA of cells from the striatum of 3-NP-treated rats. DNA fragmentation was also
      evident in this region by terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling. The data suggest that striatal cells die by apoptosis
      following administration of 3-NP.

PMID- 9037432
TI  - Evidence for rhythmic firing being caused by feedback inhibition in pinch
      inhibited raphe magnus neurons.
AB  - Raphe magnus cells that are inhibited by skin pinching fire spontaneously with
      strongly preferred interspike intervals (mean cycle 85 ms, n = 33). In
      pentobarbital-anesthetized rats, mid-cycle cathodal activation (0.3 ms) or end
      cycle anodal black (30-60 ms) at approximately 1 Hz through the extracellular
      recording microelectrode delayed expected spikes; respective post-stimulus
      latencies peaked on average at 1.17 (n = 14) and 0.40 (n = 6) cycles. Feedback
      inhibition following random excitation, but not free-running intrinsic or
      afferent oscillations, may therefore cause the rhythm.

PMID- 9037433
TI  - Preferential localization of monoamine oxidase type A activity in neurons of the
      locus coeruleus and type B activity in neurons of the dorsal raphe nucleus of the
      rat: a detailed enzyme histochemical study.
AB  - Using enzyme histochemistry for monoamine oxidase (MAO) activity, we have
      examined whether MAO type A or type B or both are localized in neurons of the
      locus coeruleus (LC) and dorsal raphe nucleus (DR) of the rat. After pretreatment
      with various concentrations of the MAO type A inhibitor clorgyline or the type B
      inhibitor deprenyl, non-fixed frozen sections of the brain were histochemically
      stained for MAO activity with tyramine as a common substrate for the two types.
      MAO activity of the stained neuron was determined by measuring optical density of
      the staining. Percentage inhibition of the control MAO activity was plotted
      against increasing concentrations of the inhibitors. MAO activity of LC neurons
      was inhibited by low concentrations of clorgyline with a monophasic dose-response
      curve but not with a biphasic curve. Higher concentrations of deprenyl were
      needed to inhibit of LC neurons. MAO activity of DR neurons was inhibited by low
      concentrations of deprenyl with a monophasic dose-response curve. Clorgyline
      inhibited the MAO activity of DR neurons at only higher concentrations. When the
      sections without inhibitor pretreatment were incubated with the type A
      preferential substrate serotonin, the MAO activity was strongly stained in LC
      neurons but very weakly in DR neurons. With the type B preferential substrate
      beta-phenylethylamine, the staining was intense in DR neurons while very faint in
      LC neurons. These findings suggest that (i) almost all the MAO activity in LC
      neurons is of type A, and (ii) the MAO activity in DR neurons is predominantly of
      type B.

PMID- 9037434
TI  - Membrane currents elicited by the organic calcium channel blocker verapamil in
      native and rat brain RNA-injected oocytes of Xenopus laevis.
AB  - For further analysis of the action of the diphenylalkylamine verapamil (CAS 152
      11-4), the ability of verapamil to elicit membrane currents by itself was
      investigated in native and rat brain. RNA-injected oocytes of Xenopus laevis.
      Administration of verapamil elicited inward currents which remained constant or
      increased slightly during ongoing application. In native and RNA-injected oocytes
      the current responses were similar in shape, but larger in size in RNA-injected
      oocytes. The currents increased up to the maximal tested concentration of 1
      mmol/l verapamil; the threshold concentration was below 80 mumol/l. After removal
      of follicular tissues the verapamil response was nearly doubled. During verapamil
      administration the input resistance was increased up to 1.7 of the initial value.
      The current response to verapamil can be subdivided into an early and late
      component. The equilibrium potential of the early component ranged between -80
      and -110 mV; the late component which increased slightly during verapamil
      application, had an equilibrium potential between 0 and -20 mV. Under the
      influence of potassium channel blockers (tetraethylammonium and cesium chloride)
      or chloride channel blockers (anthracene-9-carbonic acid and the indanyloxy
      acetic acid derivative IAA-94) the verapamil induced currents were reduced. Thus,
      the results indicate that beside the calcium channel-blocking effect, verapamil
      can induce currents by itself, presumably by acting on the potassium and chloride
      leakage.

PMID- 9037435
TI  - Studies on the abstinence-like overshoot following reversal of the potent 19
      isoamyl derivative of etorphine with naloxone. A comparison with the opioids
      fentanyl and alfentanil.
AB  - Reversal of opioid-related respiratory depression is often accompanied by an
      "acute abstinence like syndrome" with hypertension, tachycardia, and pain. This
      overshoot was used to investigate the extent at which opioids of high potency but
      different structure are involved in naloxone-induced abstinence. In 10 awake and
      trained mongrel dogs two highly mu-selective compounds, alfentanil and fentanyl,
      were given in cumulative doses and at different occasions (30-60-120-240
      micrograms/kg, and 6-12-24-48 micrograms/kg, respectively). Subsequently, a high
      dose of naloxone (100 micrograms/kg) was given at 5 min intervals while arterial
      blood gases, blood pressure, heart rate and the somatosensory evoked potential
      (SEP) were measured continuously. Following a wash-out period, the 19-isoamyl
      derivative of etorphine (M-140; 10,000 times more potent than normorphine and a
      4.5 fold potency of ethylketocyclazocine in a bioessay preparation) was also
      given in increasing doses (0.2-0.4-0.8-3.2 micrograms/kg). Again, naloxone was
      given (100 micrograms/kg) at 5 min interval, while cardiovascular parameters,
      blood gases and SEPs were measured continuously. All three opioids induced a dose
      related respiratory depression with hypercarbia and hypoxia, a dose-related
      bradycardia, and a modest hypotension. This was accompanied by a dose-related
      depression of the amplitude of the SEP, reflecting the degree of blockade of
      nociceptive afferents. Naloxone was sufficient to reverse respiratory impairment
      after fentanyl, alfentanil and M-140. However, in contrast to fentanyl and
      alfentanil, there was no cardiovascular or evoked potential overshoot following
      naloxone reversal of M-140. After alfentanil naloxone increased blood pressure,
      heart rate and amplitude of the SEP by 7%, 41% and 38%, respectively. After
      fentanyl this increase in blood pressure, heart rate and amplitude of the SEP was
      17%, 43% and 96%, respectively. The study indicates that the more potent the
      opiate mu ligands are the more is naloxone liable to induce a hyperexcitatory
      state of the cardiovascular system and an increase of nociceptive stimuli to pain
      modulating centres. After M-140 reversal of mu-related respiratory depression by
      naloxone was possible. However, no precipitation on an acute abstinence-like
      syndrome affecting antinociception or inducing cardiovascular overshoot was
      observed. This may stem from an intense binding and slow dissociation of the
      ligand from the receptor site or may be due to high binding affinity to both the
      mu and the kappa receptor site. Opioids which interact with various receptor
      sites may be of clinical interest for substitution therapy in opioid dependent
      addicts.

PMID- 9037436
TI  - Effect of mivazerol on myocardial lactate production, blood flow and
      electrocardiographic signs of ischaemia induced by coronary artery ligation in
      the anaesthetised dog.
AB  - Ischaemic injury in a number of animal models is reduced by mivazerol (2-hydroxy
      3-[(1-H-imidazol-4-yl) methyl]-benzamide, CAS 125472-02-8). This effect was
      accompanied by a reduction in heart rate. The effect of mivazerol on myocardial
      blood flow and lactate production in the ischaemic myocardium was examined at
      constant heart rate by right atrial pacing in an anaesthetised open-chest dog
      model. Three periods of ischaemic were induced by coronary occlusion for 5 min.
      The first (sham) and the second in the absence of the drug and the third 15 min
      after 10 nmol/kg i.v. Arteriovenous differences in plasma lactate using a local
      vein and coronary sinus draining the ischaemic and non-ischaemic myocardium,
      respectively, were measured before and after 4 min after coronary occlusion.
      Blood flow (microspheres) was determined at 3 min of ischaemia. Mivazerol reduced
      lactate production by the ischaemic area from 2.6 +/- 1.2 to 1.5 +/- 0.9 mmol/l
      (paired t-test, p < 0.01), but blood flow to the ischaemic sub-endocardium was
      not changed: 0.19 +/- 0.1 vs 0.21 +/- 0.12 ml.g-1.min-2. Mean ST segment
      elevation tended to be reduced 1.6 +/- 1.0 vs 3.8 +/- 3.0 mV (one-sided paired t
      test, p = 0.05). Mivazerol exerts its anti-ischaemic effect at least in part by a
      reduction in ischaemic lactate production but not by increasing ischaemic blood
      flow.

PMID- 9037437
TI  - Antithrombotic effects of the novel inhibitor of thrombin-induced offtelet
      aggregation and thrombus formation, 3-[2-[1,1':2',1"]-terphenyl-4'
      yl)ethyl]phenoxyacetic acid.
AB  - The new compound 3-[2-([1,1':2,1"]-terphenyl-4'yl)ethyl]phenoxyacetic acid
      (F1070) was synthesized and its effects on platelet aggregation induced by
      thrombin, thrombin receptor agonist peptide (TRAP), ADP and collagen were
      evaluated in humans, guinea pigs and rats, and were compared with the effects of
      he thrombin antagonists argipidine and (D)Phe-Pro-Arg-CH2Cl (FPR). F1070
      inhibited the platelet aggregation induced by these agonists and was highly
      selective in its inhibition of thrombin. F1070 inhibited fibrin formation induced
      by thrombin, but far less effectively than argipidine. In a guinea pig model of
      extracorporeal circulation thrombosis, F1070 (10 mg/kg p.o.) significantly
      inhibited the development of a thrombus. F1070 is thus a key compound that should
      facilitate the development of new orally active antithrombotic drugs that are
      specific for thrombin.

PMID- 9037438
TI  - Increased haemorrhagic risk after repeated infusion of highly substituted medium
      molecular weight hydroxyethyl starch.
AB  - Infusion of the large volumes of high molecular weight hydroxyethyl starch (HES)
      has been know to lead to coagulation disorders. Medium molecular starch is
      considered a safe alternative, even after repeated administration. In 10 patients
      with cerebrovascular diseases, a 10-day hemodilution was carried out using 10%
      HES 200/0.62. Initially, a loading dose of 500 ml was administered once over 45
      60 min, followed by 500 ml maintenance dose per day for 10 days. Its high
      intravascular molecular weight (120,000 D) showed that cleavage of the starch is
      slowed due to the higher degree of substitution. The continuous increase of HES
      serum concentration to 27.7 mg/ml gave evidence of a cumulation of poorly
      degradable molecules. Although this caused a prolonged volume effect, plasma
      viscosity and erythrocyte aggregation were influenced in an unfavourable way. The
      negative effects were not evident in their influence on the coagulation system.
      Under therapy, a significant 42.8% increase (p < 0.01) in activated partial
      thromboplastin time occurred. Factor VIII:C, von Willebrand ristocetin co-factor
      and von Willebrand factor antigen dropped during the therapy below the
      hemostasiological limit of 30% (p < 0.01), and in some patients below 10%. A high
      degree of substitution, particularly after repeated infusion, leads to a
      cumulation of large molecules that are difficult to break down and which
      unfavourably affect rheological and hemostasiological parameters.

PMID- 9037439
TI  - Studies on the metabolism of the new antidiabetic agent pioglitazone.
      Identification of metabolites in rats and dogs.
AB  - Metabolic studies of pioglitazone (CAS 105355-27-9, AD-4833), a new agent, in
      rats and dogs using liquid chromatography/tandem mass spectrometry and 1H-nuclear
      magnetic resonance led to characterization of the following metabolites; the
      parent compound, (+/-)-5-(p-hydroxybenzyl)-2-4-thiazolidinedione (M-I), (+/-)-5
      [p-[2-(5-ethyl-2-pyridyl)-2-hydroxyethoxy]benzyl] -2,4-thiazolidinedione (M-II),
      (+/-)- 5-[p-[2-(5-acetyl-2-pyridyl)ethoxy]benzyl]2,4-thiazolidinedione (M-III),
      (+/-)-5-[p-[2-[5-(1-hydroxyethyl)-2- pyridyl]ethoxy]benzyl]-2,4-thiazolidinedione
      (M-IV), (+/-)-5-[p-[2-(5- carboxymethyl-2-pyridyl)ethoxy]- benzyl]-2,4
      thiazolidinedione (M-V), and (+/-)-5-[p-[2-(5-carboxy-2- pyridyl)ethoxy]benzyl]
      2,4-thiazolidinedione (M-VI). Pioglitazone is considered to be metabolized by
      cleavage of aliphatic C-O bond to lead to M-I, hydroxylation of aliphatic
      methylene groups to form M-II and M-IV, oxidation of M-IV to give M-III,
      oxidation of the ethyl group to form M-V, and oxidative loss of the terminal
      carbon to lead to M-IV. Furthermore, part of metabolites exist as conjugated
      form. Among the conjugates, M-IV conjugated with sulfuric acid and M-V conjugated
      with taurine were identified.

PMID- 9037440
TI  - Disposition of the new antidiabetic agent pioglitazone in rats, dogs, and
      monkeys.
AB  - The disposition of pioglitazone (CAS 105355-27-9, AD-4833) was studied after oral
      administration to rats, dogs, and monkeys using 14C-labeled drug. After oral
      dosing, pioglitazone was well absorbed from the gastrointestinal tract at an
      extent of 96, 95, and 90% in rats, dogs, and monkeys, respectively. In rats, the
      concentration of pioglitazone in plasma reached a peak (Cmax 0.71 micrograms/ml)
      at 4 h (tmax) after dosing and declined with a half-life (t1/2) of 2.6 h. In
      dogs, tmax, Cmax and t1/2 were 0.5 h 0.32 micrograms/ml and 2.1 h, and those for
      monkeys were 4.3 h, 0.43 micrograms/ml and 5.3 h, respectively. The drug was
      metabolized mainly to M-I to M-VI including the pharmacologically active
      metabolites (M-II, III and IV). The pharmacologically active compounds (total of
      the unchanged compound and the above three active metabolites) accounted for 87,
      71, and 73% of the radioactivity in plasma of rats, dogs and monkeys,
      respectively. The radioactivity was widely distributed in tissues after oral
      administration to rats, and decreased to the very low concentration within 24 to
      72 h after dosing. Radioactivity dose was almost completely excreted in urine and
      feces.

PMID- 9037441
TI  - Synthesis and antihyperlipaemic activity of some novel N-cyanovinylformamidines.
AB  - Potent antihyperlipaemic activity has been observed in a series of novel N
      cyanovinylformamidines when tested in hyperlipaemic rats. Two of the compounds
      (11 and 15) were found more potent than gemfibrozil at 50 mg/kg/d dose level in
      reducing serum cholesterol and triglyceride levels and also in elevating serum
      HDL level. A good three-dimensional structural similarity has been observed
      between these two compounds and clofibrate and gemfibrozil, respectively. Acute
      toxicity studies carried out in mice indicated compound 11 to be safe even at a
      dose level of 4.5 g/kg. The title compounds were synthesized by the reaction of
      alpha-cyanoketene S,N-acetals with formamidineacetate under controlled reaction
      conditions.

PMID- 9037442
TI  - Cardiotoxic effects of salmeterol in comparison with salbutamol on the isolated
      perfused Langendorff-heart of the rat.
AB  - beta 2-Adrenoceptor agonists used in the relief of bronchospasm have long been
      known to produce circulatory side-effects. Salmeterol (CAS 89365-50-4) is a novel
      long acting highly selective beta 2-agonist. We used the Langendorff-heart rat
      model (constant perfusion pressure) to compare the direct effects of salbutamol
      (CAS 18559-94-9, SAL) and salmeterol (SMT) on the cardiac performances and their
      toxic cardiac effects (induced by 3 mmol/l perfusate calcium). At the first step
      the concentration-effect curve was established for the maximal concentration
      (Cmax) of salbutamol leading to the maximal chronotropic effect on the heart for
      20 min after a 20 min stabilization period (basal values). All hearts were
      consequently submitted to a 20 min Krebs-Henseleit perfusion in order to study
      the reversibility of the myocardial performances. The types of the myocardial and
      coronary beta-adrenoceptors involved in SAL (Cmax) effects were identified using
      a selective beta 1 (atenolol) and a beta 2 (butoxamine) antagonist. SAL induced
      an increase in the heart rate via a selective stimulation of the beta 1
      adrenoceptors (beta 1-AR). SMT appeared to be more potent than SAL on the heart
      rate. Direct toxic drug effects on the heart appeared gradually with SAL whereas
      they appeared sharply at the highest concentration of SMT. The enzyme leakage
      observed during the recovery period was more pronounced with SMT than SAL.
      Perhaps, this phenomenon might be due to the lipophilicity of SMT. However, these
      direct cardiac effects of SMT have to be considered in association with its
      airway smooth muscle relaxant effect (therapeutic effect) which has been proven
      much more potent than those of SAL. Therefore SMT was less cardiotoxic than SAL
      at similar therapeutic concentrations.

PMID- 9037443
TI  - Comparison of bronchodilating effects of two salbutamol dry powder inhalers in
      asthmatic patients.
AB  - In an open, randomized crossover study two different types of dry powder inhalers
      (DPIs) were compared. Twenty-five adult asthmatic patients inhaled a single dose
      of 200 micrograms of salbutamol (CAS 18559-94-9) on two separate days. Salbutamol
      was administered either from a novel multidose DPI (Easyhaler, test DPI) or from
      another type of DPI (reference DPI). On both study days lung function, blood
      pressure and heart rate were measured during a 4-h follow-up period. Both powder
      inhalers caused a clear increase in lung function parameters. The mean (SD)
      maximum forced expiratory volume in 1 s (FEV1) after the test DPI was 3.25 (1.30)
      1 and after the reference DPI 3.28 (1.29) 1. The mean relative change from the
      baseline in FEV1 was similar after administration of both preparations. The mean
      area under the curve (AUC0-4h) of the absolute FEV1 values was 729 (316) and 731
      (309) 1 x min after test and reference DPIs, respectively. The salbutamol doses
      had no clinically significant effects on blood pressure or heart rate and were
      equally well tolerated. Furthermore, 41% of patients preferred the test DPI and
      19% the reference DPI, while 40% felt there was no difference between the
      devices. In conclusion, the results of this study show that the test DPI, a novel
      multidose powder inhaler, is an effective, safe and convenient alternative when
      an inhaled bronchodilator treatment is considered for an obstructive patient.

PMID- 9037444
TI  - Omeprazole, amoxicillin and bismuth for peptic ulcer healing and Helicobacter
      pylori eradication.
AB  - A controlled, randomized study was performed in patients with active peptic ulcer
      disease and positive Helicobacter pylori (Hp) status to assess the clinical
      efficacy (endoscopic healing and eradication of Hp) of different combined
      treatments. In the first part of the study a treatment with omeprazole (CAS 73590
      58-6) (40 mg once daily) alone (group A) or in combination with tripotassium
      dicitrato bismuthate (TDB; 240 mg bid, group B) for 4 weeks was evaluated in 20
      and 13 patients, respectively. As expected healing rates were high and comparable
      (75 vs. 85%), however, Hp-eradication was zero in both groups. In the subsequent
      second part of the trial group A (n = 19) received omeprazole (20 mg bid) for 2
      weeks + amoxicillin (CAS 26787-78-0) tablets (1 g bid only 2nd week). Accumulated
      healing rate increased to 95% but Hp-eradication was 37%. From group B only 8
      patients participated in a second 4-week course of monotherapy with TDB. Whereas
      healing occurred in all individuals, Hp-eradication was still low (12.5%). In
      addition plasma levels (omeprazole, Bi) and urinary excretion (Bi) were monitored
      to test whether drug interaction and/or noncompliance of the patients could help
      to explain the clinical findings. Systemic availability of Bi was increased by
      the coadministration of omeprazole and plasma levels of omeprazole were in
      general higher in Hp-positive patients if compared to those of Hp-negative
      patients. The following conclusions could be drawn from the 4 parts of the study:
      Treatment of peptic ulcer disease with omeprazole either alone or in combination
      with TDB is effective for ulcer healing but not for eradicating Hp. Omeprazole
      seems to decrease the Hp-eradicating potential of Bi probably due to a drug
      interaction. A second treatment course with TDB is apparently not of much
      benefit. One week pretreatment with omeprazole does not affect healing but might
      attenuate Hp-eradication rate of subsequent combined treatment with amoxicillin.
      One week coadministration of amoxicillin is not sufficient. The magnitude of
      omeprazole's plasma levels has no effect on Hp-eradication rates. As the numbers
      of patients in this study was relatively small these conclusions need to be
      confirmed by larger trials.

PMID- 9037445
TI  - Synthesis and biochemical/pharmacological profile of the novel leukotriene B4
      receptor antagonist sodium (1S*, 3S*)-1-hydroxy-3-[(3 R*S*,E)-3-hydroxy-7-phenyl
      1-hepten-1-yl]-1-cyclohexane acetate.
AB  - A novel series of leukotriene B4 (LTB4) antagonists is reported. These compounds
      present a cyclohexane ring in their chemical structure, which mimics the three
      conjugated double bonds of LTB4. The biochemical/pharmacological profile of the
      leader compound, PH-163 (sodium (1S*,3S*)-1-hydroxy-3-[(3R*S,E)-3-hydroxy-7
      phenyl-1-hepten-1-yl]- 1 -cyclohexane acetate, CAS 163251-41-0) is described.
      This compound competes with [3H]LTB4 binding to its receptor in human neutrophils
      and guinea pig lung membranes with IC50's of 0.8 mumol/l and 0.2 mumol/l,
      respectively, i.e. relative binding affinities of 1% as compared to LTB4. PH-163
      does not elicit any agonist activity, but inhibits leucocyte chemotaxis induced
      by LTB4 (pKB = 6.57) and lung parenchymal strip contraction (IC50 = 0.1 mumol/l).
      In conclusion, PH-163 or derivatives could be useful in the treatment of
      inflammatory diseases where LTB4 seems to be involved.

PMID- 9037446
TI  - Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8
      tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 1st
      communication: absorption, distribution, metabolism and excretion after topical
      application and subcutaneous administration in rats.
AB  - 4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid
      (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have
      a potent topical antipsoriatic activity. The pharmacokinetic profiles of Am-80
      were studied in rats after topical application and subcutaneous administration of
      14C-labeled Am-80. After topical application at a dose of 1 g ointment (0.1%)/kg
      to normal skin rats by the occlusive dressing technique, radioactivity was
      scarcely detected in the blood or plasma. In the stripped skin rats, plasma
      radioactivity reached the peak at 2 h and decreased with a half-life of 5.5 h.
      The recovery of radioactivity in the excreta and carcass amounted to 54.7% of the
      dose, indicating about six times higher absorption than that in the normal skin
      rats. After subcutaneous administration at a dose of 1 mg/kg, the maximum
      concentration of blood radioactivity was attained at 1-2 h and declined with a
      half-life of 4-5 h until 24 h. Biliary excretion was about 80% of the dose, and
      enterohepatic circulation was estimated to be 36.5%. Radioactivity was
      distributed systemically, particularly in abundance in the liver followed by
      adrenal gland and kidney. Elimination of radioactivity in most tissues was
      extremely slow and the radioactivity was detected even at 240 h after dosing.
      There was no gender-related difference in the profile of distribution and
      elimination of 14C-Am-80 in the rats. Two major metabolic pathways in rats have
      been postulated for Am-80; one involves the 6- or 7-hydroxylation to yield
      related hydroxy-Am-80 that lead to the formation of oxo-Am-80, and another
      involves the hydrolysis of the carboxamide bond to yield tetrahydro-tetramethyl
      naphthalenylamine and terephthalic acid. Furthermore, Am-80 itself an 6- or 7
      hydroxy-Am-80 were susceptible to the formation of taurine conjugates. In the
      plasma, unchanged Am-80 was present in a high proportion to total radioactivity,
      while in the urine and bile the proportion of unchanged Am-80 was low.

PMID- 9037447
TI  - New antiinfectious biomaterials. Ciprofloxacin containing polyurethanes as
      potential drug delivery systems to prevent foreign-body infections.
AB  - Device related infections are an increasing problem since foreign materials are
      used in modern medicine. Ciprofloxacin-HCl salt (CAS 86393-32-0) and lipophilic
      ciprofloxacin-betaine (Bay o 9867) incorporated into polyurethanes by solvent
      casting technique were studied in order to develop antiinfectious properties of
      this biomaterial. Drug release rates, bacterial colonization and morphological
      features of the polymerciprofloxacin combinations were studied and the physico
      chemical mechanisms of the delivery were discussed. Ciprofloxacin salt showed a
      fast initial release rate, whereas ciprofloxacin-betaine was characterized by a
      more continuous release behaviour. A higher diffusity of the lipophilic
      ciprofloxacin-betaine in the polymer could be shown as compared to its salt
      incorporated into the polyurethane. The high initial burst effect of the
      hydrochloride antibiotic was caused by its high solubility in the elution medium.
      Bacterial colonization to the antibiotic-loaded polyurethanes was inhibited
      effectively only by preparations showing a slower but more sustained drug
      release. Scanning electron microscopy (SEM) demonstrated that the polyurethane
      antibiotic combination was most homogenous for ciprofloxacin-betaine.
      Polyurethane material loaded with ciprofloxacin salt showed crystals at the
      surface and a granular structure of the polymeric matrix. Crystalline structure
      of the drug on polymeric surfaces varied with loading concentration and
      lipophilicity. Physico-chemical similarity of the polymeric material and the
      antibodies is important for the homogeneity of the polymer-antibiotic
      combinations. High homogeneity is required for a sustained and prolonged release
      and effective inhibition of bacterial colonization.

PMID- 9037448
TI  - Trypanocidal activity of synthetic heterocyclic derivatives of active quinones
      from Tabebuia sp.
AB  - Continuing a program on the chemistry and biological activity of compounds from
      the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of
      nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained
      from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with
      amino-containing reagents has been studied. Also for the first time the
      biological activity of allyl derivatives of lawsone, a natural quinone from
      Lausonia alba inactive against T. cruzi, is reported. The introduction of an
      allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that
      showed activity against the parasite, with ID50 values of 420.7 +/- 71.1 and
      330.7 +/- 62.4 mumol/l, respectively. The trypanocidal activity of the naphtho
      heterocyclics synthesized from the original quinones showed no concordant
      behavior in relation to the parent compound. Six of nine of the synthesized
      compounds presented lower ID50 values than crystal violet, indicating a general
      trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type.
      However, their chemical structures do not endow them with the capacity of free
      radical generation by biological reduction as the quinoidal moiety, nor do they
      have chemical reducible appendage like the nitro group of nifurtimox and
      benznidazole, responsible for such behaviour. As a hypothesis, the pattern of
      their biological actions should be focused in other aspects of their chemical
      structures. Because of their polycyclic planar topology, these derivatives are
      potential candidates for experimental tests as DNA intercalating agents.

PMID- 9037449
TI  - Subacute toxicity of a Pseudomonas vaccine prepared from outer membrane fraction
      of Pseudomonas aeruginosa in beagle dogs.
AB  - CFC-101, a Pseudomonas vaccine, was administered to beagle dogs by intramuscular
      injection for 4 weeks (5 days/week) at 0.05, 0.15 and 0.45 mg/kg/d. Clinical
      signs considered to be related to treatment were restricted to swelling at the
      injection sites, being apparent 1-2 h after treatment. There was no effect on
      body weight, food consumption, ophthalmoscopy, electrocardiography, hematology,
      biochemical and urinary parameters. The histopathological examination revealed
      treatment-related changes at the injection sites at all dosages, particularly in
      the hindlimbs where both perivascular and intramuscular aggregations of
      inflammatory cells were seen. Thus, the only treatment-related changes seen in
      this study were local reactions to the test substance at the injection sites;
      furthermore these changes seem to represent a pharmacological response to the
      test material. Because no evidence of any systemic toxicity was observed at any
      dosage level, it is concluded that dosages of CFC-101 up to and including 0.45
      mg/kg/d were well tolerated over a period of 4 weeks in the beagle dog.

PMID- 9037450
TI  - Effect of early treatment with praziquantel on serum connective tissue metabolite
      markers in children and adolescents with intestinal schistosomiasis mansoni.
AB  - This work was designed to assess the reflection of early treatment by
      praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) on serum connective tissue
      metabolite markers (hyaluronic acid and procollagen III peptide) in patients with
      active intestinal schistosomiasis. Children and adolescent subjects from primary
      and secondary schools in an endemic area of schistosomiasis mansoni were
      included. Age-matched subjects from an urban area served as normal controls. All
      subjects were examined clinically and parasitologically. Detection of hepatitis B
      seromarkers was also done. The infected subjects were treated with praziquantel
      at a dose of 60 mg/kg of body weight which was repeated after 4 weeks. Serum
      hyaluronic acid and procollagen III peptide were measured by radioimmunoassay.
      High hyaluronic acid was encountered in infected subjects when compared to their
      respective age-matched controls. Significant decrease of 4 and 8 weeks post
      treatment was noted when compared to ist level before treatment. There was no
      significant change in serum procollagen III peptide on comparing infected
      subjects to their controls, whereas a significant increase was observed in its
      level after 4 and 8 weeks post-treatment compared to that before treatment. This
      work suggests that early treatment of intestinal schistosomiasis with specific
      chemotherapy (praziquantel) decreases serum hyaluronic acid and increases
      procollagen III peptide probably via downregulation of granulomatous inflammatory
      cell reaction and activation of collagenase enzymes, respectively.

PMID- 9037451
TI  - Detection of DNA damage in stimulated human lymphocytes after adding cytostatic
      drugs in vitro. A model to demonstrate individual damage rates.
AB  - The DNA damaging effect of different concentrations of methotrexate, 6
      mercaptopurine, 6-thioguanine and cisplatin was tested by nucleoid sedimentation
      in pokeweed mitogen (PWM)-stimulated lymphocytes of 16 healthy persons in vitro.
      The examined persons show an individual variation of DNA damage demonstrating
      individual differences in DNA repair. The method can be used to identify persons
      with a low DNA repair capacity, and possible cytogenetic side effects of
      cytostatic drugs can be calculated before starting a cancer therapy. In clinical
      practice the use of cytostatic drugs is limited because of the side effects on
      normal tissues. The cancer therapist can improve a cytostatic therapy when he
      obtains information about possible DNA damage of cytostatic drugs in cells of the
      patient at the beginning of the therapy.

PMID- 9037452
TI  - Evaluation of cardiac subacute toxicity of epirubicin, chlorambucil, cisplatin,
      methotrexate and a homo-aza-steroid ester with antitumor activity in rats using
      serum biochemical parameters.
AB  - Cardiac subacute toxicity induced by the antineoplastic drugs epirubicin (CAS
      56390-09-1), chlorambucil (CAS 305-03-3), cisplatin (CAS 15663-27-1) and
      methotrexate (CAS 59-05-2) and the steroid alkylating agent 3 beta-hydroxy-13
      alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13, 17-lactam ?p-[bis(2
      chloroethyl)amino] phenyl? acetate was investigated in rats using serum
      biochemical parameters. Toxicology evaluation was performed in serum samples
      following the administration of dose regimens of the agents that were previously
      shown to be effective in suppressing malignant tumor growth or to prolong
      survival in tumor-bearing animals. Cardiac subacute toxicity was evaluated by
      measuring serum enzyme activity of creatine kinase, creatine kinase isoenzyme-MB,
      lactate dehydrogenase and aspartate aminotransferase. The use of the above serum
      biochemical parameters indicated that the cardiac subacute toxicity impact of the
      antitumor drugs was epirubicin "methotrexate = chlorambucil = cisplatin > homo
      aza-steroid ester.

PMID- 9037453
TI  - Studies on the phototoxic effects of oral antidiabetics and diuretics.
AB  - A number of sulphonamide derived oral antidiabetics (chlorpropamide,
      glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide) and
      diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothaizide,
      bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide,
      hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and
      xipamide) were investigated for phototoxicity in a cell culture model. Cell death
      dependent on UVA fluence and test substance concentration was observed in the
      presence of the oral antidiabetics glibenclamide and gliquidone, as well as the
      diuretics bemetizide, bendroflumethiazide, benzylhydroxhlorothiazide, bumetanide,
      butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and
      trichlormethiazide. Bendroflumethiazide was phototoxic at 5 x 10(-5) mol/l and
      higher concentrations, bemetizide, benzylhydrochlorothiazide, bumetanide and
      hydroflumethiazide were phototoxic at 2.5 x 10(-4) mol/l and higher
      concentrations, and the oral antidiabetics glibenclamide and gliquidone as well
      as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and
      trichlormethiazide were phototoxic at 5 x 10(-4) mol/l and higher concentrations.
      The oral antidiabetics chlorpropamide, glipizide, glymidine, tolazamide and
      tolbutamide as well as the diuretics chlortalidone, furosemide, indapamide and
      xipamide did not induce phototoxicity in this assay.

PMID- 9037454
TI  - Drug research--a change of paradigms.

PMID- 9037455
TI  - Modern pharmaceutical biotechnology. Situation worldwide and in Germany 1995.
AB  - A variety of new diagnostics and drugs have been developed with the aid of modern
      biotechnology which has opened up new medical possibilities and will yield novel
      solutions in the future. The remarkable dynamics of the innovation process in the
      pharmaceutical sector is reflected by the number of drugs under development. In
      1995, 771 projects were known to be in development worldwide. The leadership of
      North America in research and development of drugs from modern biotechnology is
      clearly demonstrated. Whereas the number of development recombinant DNA products
      remained practically constant in the triade (North America, Europe, Japan), the
      number of preclinical and clinical somatic gene therapy projects increased
      considerably in 1995 compared to 1994 in the United States and in Europe; Japan
      is virtually absent in this new emerging research field. In Europe, the vast
      majority of drugs from modern biotechnology, are developed in Great Britain,
      Germany, Switzerland, France, the Netherlands, and Italy. The number of gene
      therapy projects show a remarkable growth of more than 60% in 1995 compared with
      1994; at the same time, the absolute and relative share of recombinant DNA
      products decreased distinctly. In Germany, about two thirds of the development of
      biotechnological drugs are conducted in cooperation with a foreign partner,
      mostly hightech companies from the United States. A variety of drugs manufactured
      with modern biotechnology, however, has not only provided significant medical
      progress and has closed therapeutic gaps but has also demonstrated considerable
      economic success. In 2000, further significant growth is expected especially for
      growth factors and cytokines.

PMID- 9037477
TI  - Immunohistochemical localization of ADP-ribosylarginine hydrolase in rodent CNS.
AB  - Polyclonal antibodies were generated against ADP-ribosylarginine hydrolase (AAH),
      using recombinant fusion protein of rat AAH and glutathione-S-transferase as a
      immunogen, and affinity-purified. Western blotting showed that the antibodies
      recognized in mouse brain homogenate a single protein with a molecular mass of 38
      kDa, the expected size for mouse AAH. An analysis using the antibodies revealed
      that heavy labelings were apparent in various brain regions. In the cerebral
      cortex, pyramidal cells in layers III and V were the most heavily labeled. In the
      hippocampal formation, labeling was present on the pyramidal neurons and granule
      cells. The most heavily immunostained cell type was the pyramidal neuron of CA3.
      In the cerebellum, Purkinje cells were the most heavily labeled. Less intense
      staining was present over the granule cells. In the basal ganglia, neurons in the
      caudate nucleus and large multipolar cells in the amygdaloid complex were
      immunoreactive. Heavy labeling was seen in many midbrain and brainstem nuclei.
      Neurons in the habenula and ependymal cells were stained heavily. On Western blot
      analysis of rat cerebrospinal fluid (CSF), the anti-AAH antibodies recognized a
      protein with a molecular mass of 38 kDa. This is apparently the first evidence of
      a widespread but distinctive distribution of AAH in neurons of mouse brain and
      the presence of extracellular AAH in rat CSF.

PMID- 9037478
TI  - Opioid receptor-coupled G-proteins in rat locus coeruleus membranes: decrease in
      activity after chronic morphine treatment.
AB  - The nucleus locus coeruleus is involved in the expression of opiate physical
      dependence and withdrawal, and has been characterized extensively with regard to
      chronic morphine-induced alterations in biochemical and electrophysiological
      responses. In the present study the effects of chronic morphine treatment on
      opioid receptor-coupled G-protein activity was investigated in membranes from rat
      locus coeruleus. Opioid agonists stimulated low Km GTPase activity with
      pharmacology consistent with mu receptors. Chronic morphine treatment resulted in
      decreases in both basal and opioid-stimulated low Km GTPase activity, with no
      change in the percent stimulation by agonist. The decrease in low Km GTPase
      activity appeared to be due to a decrease in the Vmax of the enzyme, with no
      change in the Km for GTP hydrolysis. These results were confirmed by assays of
      basal and opioid receptor-stimulated [35S]GTP gamma S binding in the presence of
      excess GDP. Thus, chronic morphine treatment apparently decreased inhibitory G
      protein activity in the locus coeruleus without producing any detectable
      desensitization. These results suggest a potential adaptation at the
      receptor/transducer level which may contribute to other biochemical changes
      produced in the locus coeruleus by chronic morphine treatment.

PMID- 9037479
TI  - Neurotrophin-3 promotes the survival of oligodendrocyte precursors in embryonic
      hippocampal cultures under chemically defined conditions.
AB  - embryonic rat hippocampal cells were cultured in basal medium with or without
      addition of the neurotrophin NT-3. After culturing in these extreme conditions,
      the effects of NT-3 on the neuronal and on the glial components were assessed.
      Neurons survived even in the absence of NT-3 but failed to reach terminal
      differentiation. On the other hand, NT-3 promoted the survival but not the
      proliferation and/or the differentiation of oligodendrocytes precursors present
      in the same culture, an effect that was reversed by the addition of neutralizing
      antibodies against NT-3. Type I or II astrocytes were not affected by NT-3. These
      results reinforce the role for NT-3 in oligodendrocyte lineage development and
      allow to dissect the roles of this neurotrophin in survival and in
      proliferation/differentiation of oligodendrocytes.

PMID- 9037480
TI  - Regional distribution of neural cell adhesion molecule immunoreactivity in the
      adult rat telencephalon and diencephalon. Partial colocalization with heparan
      sulfate proteoglycan immunoreactivity.
AB  - In the present paper immunocytochemical analysis at the fluorescence
      microscopical level has been performed of neural cell adhesion. molecule (NCAM)
      immunoreactivity in the adult rat tel- and diencephalon in order to further
      substantiate the highly selective neuronal localization of NCAM immunoreactivity,
      using an affinity purified rabbit antiserum recognizing homologous NCAM proteins
      from rat brain. Also, double immunolabelling experiments were performed with
      monoclonal antibodies specific for heparan sulfate related epitopes or gamma
      aminobutyric acid (GABA) to establish in which cell populations a colocalization
      existed with immunoreactive heparan sulfate proteoglycans of GABA. Within the
      neocortex NCAM immunoreactivity was exclusively localized to the area of the cell
      membrane of soma and proximal dendrites of subsets of large pyramidal nerve cells
      of the layer 5 of the frontoparietal cortex. Within the dorsal hippocampus, the
      NCAM immunoreactivity was exclusively located to the cell surface area of the
      pyramidal cell bodies of area CA2. Two colour immunofluorescence procedures
      demonstrated a colocalization of NCAM and 3G10 but not 10E4 immunoreactivities in
      the cell surface area of many of the NCAM-positive nerve cell bodies of these two
      regions. Within the thalamus, strong NCAM immunoreactivity was exclusively
      demonstrated at all rostrocaudal levels of the reticular thalamic nucleus. The
      horizontal band of NCAM immunoreactivity was not continuous, but split up into
      patches of NCAM immunoreactivity within groups of nerve cell bodies. When
      analysing the number of cells per unitary square in the rostrocaudal direction, a
      significant increase of positive cells was found in the rostral and middle thirds
      versus the caudal third of the reticular thalamic nucleus. Many of the cell
      bodies with NCAM immunoreactivity in their cell surface are showed cytoplasmic
      GABA immunoreactivity. In the three regions shown to contain NCAM
      immunoreactivity, proteins of the NCAM type may play a special role for the
      maintenance of the synaptic structure. The findings also suggest that the
      sulfated proteoglycans and NCAM can interact in the regulation of cell-cell
      interaction via adhesion. In the reticular thalamic nucleus NCAM molecules may be
      part of a set of cell-adhesion molecules involved in a structural organization of
      the nucleus, which allows it to play a key role in relating cortical maps to
      thalamic maps.

PMID- 9037481
TI  - Bilateral coupling in learned blinking: side superiority, synchrony and temporal
      coordination in normal cats.
AB  - In order to study interocular temporal coupling in the initiation of learned
      symmetrical blinking, experiments were carried out on cats trained to blink in
      response to a 500-ms tone paired with 100-ms airpuffs randomly delivered to
      either eye (alternate airpuff; 6 animals) or simultaneously directed to both eyes
      (bilateral airpuff; 4 animals) 400 ms after tone onset. In spite of the fact that
      differences in conditioned response (CR) latencies of the right and left eye
      varied in a wide range between positive and negative values in all subjects, a
      statistically significant difference between the mean CR latencies of the two
      eyes (further called side superiority) was found in 6 animals, of which 4 were
      trained by alternate airpuff and 2 by bilateral airpuff. Superiority of the right
      eye was found in 3 animals and the opposite was observed in the other 3. Analysis
      of the differences between CR latencies of the two eyes showed that side
      superiority was not due to the ability of one eye to give CRs consistently
      shorter than those of the other eye, but it crucially depended on the higher
      proportion of trials in which the superior eye led. The ability to give
      simultaneous CRs by the two eyes was found inversely related to the mean CR
      latency per session and subject. Regression analysis showed that power equations
      best described these relationships. In all animals, the frequency distribution of
      simultaneous CRs paralleled the frequency distribution of all CRs. In spite of a
      considerable trial-by-trial variability in the temporal relationships between CR
      latencies of the two eyes, clear-cut linear correlations were found by plotting
      the mean CR latencies of the right and left eye per both session and subject. The
      results reviewed in this paper are best accounted for by suggesting that blink
      onset of the two eyes is independently controlled by two distinct command signals
      and is modulated by bilaterally-balanced and lateralized influences.

PMID- 9037482
TI  - Hyperthermia enhances spectrin breakdown in transient focal cerebral ischemia.
AB  - Calpain-mediated spectrin degradation is triggered by cerebral ischemia and, when
      persistent, is thought to signal irreversible neuronal injury. Hyperthermia
      superimposed upon cerebral ischemia may exacerbate the injury process. In this
      study, we compared the extent of spectrin degradation in the brains of rats
      subjected to 1 h of transient proximal middle cerebral artery (MCA) clip
      occlusion performed under conditions of cranial normothermia (37 degrees C) or
      mild cranial hyperthermia (39 degrees C). Immunocytochemical localization of
      spectrin breakdown products was achieved by the use of a rabbit polyclonal
      antibody which reacted selectively with calpain-generated fragments of brain
      spectrin. The perfusion times studied were 1, 4 or 24 h. Following normothermic
      MCA occlusion, spectrin immunoreactivity was present only occasionally and only
      in scattered cortical neurons immediately upon reperfusion and 1 h later; all
      normothermic brains showed space immunoreactivity at 4 h of reperfusion; and no
      immunoreactivity was detected at 24 h. By contrast, following hyperthermic MCA
      occlusion, moderate-to-intense immunostaining was present in cortical pyramidal
      neurons even immediately upon reperfusion and persisted at 1 h of reperfusion. At
      4 and 24 h, most brains exhibited dense immunoreactivity associated with
      morphologically shrunken neurons. Following 24 h survival, semi-thick plastic
      sections revealed intact neuropil and only selective neuronal necrosis in
      normothermic rats. By contrast, pan-necrosis was evident 24 h after the
      hyperthermic ischemic insult. These results indicate that mild cranial
      hyperthermia superimposed upon transient focal ischemia markedly enhances calpain
      activation and spectrin degradation; this process appears to be an important
      mechanism by which hyperthermia exacerbates ischemic injury.

PMID- 9037483
TI  - The effects of temperature and synaptic blockade in vitro on neurons of the
      horizontal limb of the diagonal band of Broca in the rat basal forebrain.
AB  - We studied the thermosensitivity of neurons in the rat horizontal limb of the
      diagonal band of Broca (HDB) in vitro under normal conditions and under
      conditions of a low calcium/high magnesium synaptic blockade (SB). Of 52 HDB
      neurons tested, 34 neurons (65%) were warm-sensitive (WS), three neurons (6%)
      were cold-sensitive (CS), 11 neurons (21%) were temperature-insensitive (TI) and
      four additional neurons (8%) were both warm- and cold-sensitive (WS/CS). Of 34
      neurons tested for thermosensitivity under SB, 11 were WS, 4 were CS and 19 were
      TI. Nearly half (48%) of the WS neurons maintained warm sensitivity under SB, 43%
      became TI and 9% became CS. Baseline firing rates of neurons significantly
      decreased during SB and then increased during recovery from SB. In addition, a
      distinct anatomical distribution of thermosensitive neurons was found in the HDB.
      The most ventral aspect of the HDB (interaural +0.9-1.3 mm) had proportionally
      fewer temperature sensitive neurons (65% vs. 88%) than areas more dorsal
      (interaural +1.3-1.7 mm), and only one of seven ventral HDB neurons (14%)
      remained thermosensitive during SB. In the dorsal HDB, 65% of the neurons
      maintained thermosensitivity during SB. These results demonstrate that the HDB
      contains inherently thermosensitive neurons, and that a difference in thermal
      characteristics exists between the ventral and dorsal HDB neurons.

PMID- 9037484
TI  - Pharmacologic blockade of non-NMDA receptors at deep prepiriform cortex
      attenuates heat shock protein expression in global ischemia.
AB  - Deep prepiriform cortex modulates excitatory activity in the limbic system during
      seizures. We therefore studied a potential role for this system in another
      process involving excitatory neurotransmission: global ischemia in the rat. The
      non-NMDA antagonist NBQX was microinjected bilaterally into deep prepiriform
      cortex prior to 10 min of global ischemia. Hippocampal cell injury was then
      assessed by heath shock protein (HSP) expression 24 h after ischemia. NBQX
      significantly decreased the number of HSP positive cells in both CA1 and CA3
      hippocampal subsectors, suggesting the possibility that pathways from deep
      prepiriform cortex to hippocampus modulate excitotoxicity in target neurons
      during ischemia.

PMID- 9037485
TI  - Insulin-like growth factors and insulin stimulate erythropoietin production in
      primary cultured astrocytes.
AB  - Erythropoietin (EPO) is established as a major regulator of erythropoiesis.
      However, we and others have shown that neurons express erythropoietin receptor
      (EPO-R), that astrocytes produce EPO and that EPO may act as a neurotrophic
      factor in the CNS. We also found that EPO production is activated by insulin and
      insulin-like growth factors (IGFs) in astrocytes in a dose-dependent manner and
      that IGF-I was the most potent activator. The concentrations required for half
      maximal activation were 3 nM IGF-I, 10 nM IGF-II and 100 nM insulin. The oxygen
      concentration regulates EPO production; hypoxia stimulates EPO production in
      astrocytes. The stimulatory effect of IGFs and insulin on EPO production in
      astrocytes was not affected by the oxygen concentration of astrocyte culture.
      Insulin and IGFs did not increase the total protein synthesis of astrocytes but
      increased EPO mRNA levels, indicating that EPO production is stimulated at the
      mRNA level. It appeared that the growth factor-induced accumulation of EPO mRNA
      in astrocytes was caused by activation of the tyrosine kinase-signal transduction
      pathway, because tyrosine phosphorylation of receptors for IGF-I and insulin was
      activated when astrocytes were stimulated by these growth factors.

PMID- 9037486
TI  - Distribution of presumptive chemosensory afferents with FMRFamide- or substance P
      like immunoreactivity in decapod crustaceans.
AB  - In five species of decapod crustaceans--Cherax destructor (crayfish), Carcinus
      maenas (crab), Homarus americanus (clawed lobster), Eriocheir sinensis (crab),
      Macrobrachium rosenbergii (shrimp)--immunocytochemical stainings revealed the
      presence of sensory afferents with FMRFamide-like immunoreactivity in the central
      nervous system. These afferents were extremely thin, very numerous, and
      innervated all sensory neuropils except the optic and olfactory lobes. In their
      target neuropils they gave rise to condensed net- or ball-like terminal
      structures. Only in Homarus americanus but not in any other studied species
      immunocytochemistry revealed a separate, non-overlapping class of sensory
      afferents with substance P-like immunoreactivity. Also the afferents with
      substance P-like immunoreactivity were very thin and numerous, innervated all
      sensory neuropils except optic and olfactory lobes, and gave rise to condensed
      terminal structures. From their morphological characteristics it can be concluded
      that likely both classes of afferents are chemosensory. The substance P-like
      immunoreactivity suggests a link with the nociceptor afferents of vertebrates,
      with which both classes of afferents share several other morphological features.

PMID- 9037487
TI  - beta-Amyloid peptide-induced morphological changes coincide with increased K+ and
      Cl- channel activity in rat cortical astrocytes.
AB  - Alzheimer's disease (AD) is a slowly progressing neurodegenerative disease
      characterized by the loss of neurons and formation of amyloid plaques, often
      surrounded by reactive astrocytes. Astrocytes are important regulators of the
      normal neuronal environment, and changed astrocyte function may lead to increased
      neuronal vulnerability. The slow onset of the disease with a gradual increase in
      the beta-amyloid peptide (beta-AP) concentrations may alter astrocyte function
      long before any visible symptoms of the disease are observed. We, therefore,
      studied in vitro the effects of small amounts of beta-AP(1-40) and -(25-35) on
      rat cortical astrocyte function observing changes in cell morphology,
      intracellular calcium levels (Cai), and ion channel activity. Incubation with 10
      and 200 nM beta-APs caused increased process formation and hypertrophy.
      Stellation was also detected when astrocyte cultures were incubated with 1 microM
      AlCl3 alone, or together with beta-APs. Fura-2AM-loaded astrocytes were used to
      test whether the morphological changes were connected to changes in Cai levels. 1
      microM beta-AP(1-40) induced transient Cai increase in approximately 17%, and
      beta-AP(25-35) in approximately 36% of astrocytes. In patch-clamp studies,
      increased K+ and Cl- channel activity was detected with 10-100 nM beta-AP(1-40).
      With large amounts (20 microM) of beta-AP(1-40), an additional giant channel
      activity emerged. These beta-AP-induced changes in astrocyte function may
      eventually be critical for the neuronal survival in Alzheimer's disease.

PMID- 9037489
TI  - Transcytosis of 6.6-nm gold-labeled transferrin: an ultrastructural study in
      cultured porcine blood-brain barrier endothelial cells.
AB  - The mechanism and regulation of iron transport to the brain are largely unknown.
      The large surface area of the blood-brain barrier capillaries and the presence of
      transferrin receptors on the luminal plasma membranes of the blood-brain barrier
      endothelial cells (BBB-ECs) suggest that these cells actively participate in the
      transport of iron into the brain. In this paper, we describe the ultrastructural
      morphology of primary and first-passage cultures of BBB-ECs grown on different
      types of porous membranes. To investigate the mechanism of iron transport into
      and across the BBB-ECs, porous membrane grown first-passage cells were incubated
      with 6.6-nm gold-labeled transferrin and studied with electron microscopy.
      Results are suggestive for a transcytosis of transferrin through the BBB-ECs.

PMID- 9037488
TI  - Actions of S-nitrosocysteine in the nucleus tractus solitarii are unrelated to
      release of nitric oxide.
AB  - Cardiovascular effects elicited by microinjection of L-S-nitrosocysteine in the
      nucleus tractus solitarii (NTS) were compared and contrasted with those produced
      by the dextroisomer, other nitric oxide donors and nitric oxide itself. L-S
      nitrosocysteine produced dose-related decreases of arterial pressure and heart
      rate. In contrast, D-S-nitrosocysteine, S-nitrosoglutathione, glyceryl
      trinitrate, and sodium nitroprusside produced minimal responses that were not
      dose-related. Likewise, injection of cystine and nitric oxide, two products of S
      nitrosocysteine breakdown, produced no significant response. Headspace analysis
      using chemiluminescence revealed that L- and D-S-nitrosocysteine released
      identical amounts of nitric oxide when exposed to homogenates of whole rat brain.
      Responses to L-S-nitrosocysteine were not affected by local injection of
      oxyhemoglobin or the nitric oxide synthase inhibitor L-nitroarginine methylester.
      Although injection of L-cysteine into the NTS produced responses similar to those
      seen with injection of L-S-nitrosocysteine, blockade of excitatory amino acid
      receptors with kynurenic acid inhibited responses to cysteine but not those to
      the nitrosothiol. The study demonstrates that S-nitrosocysteine is biologically
      active in the NTS. Its action is independent of release of nitric oxide from the
      nitrosothiol but may be mediated through stereoselective sites on target neurons.

PMID- 9037490
TI  - Fos and Jun expression in rat supraoptic nucleus neurons after acute vs. repeated
      osmotic stimulation.
AB  - Using a double-label immunofluorescence method, we analyzed the time course of
      the appearance of Fos and Jun in the nuclei of supraoptic nucleus (SON) neurons
      following intraperitoneal injection of hypertonic saline. Fos and Jun
      immunostaining appeared within 30 min, peaked at 90-120 min, and disappeared 4-5
      h later. At all time points (30, 60, 120, 180, 240 min postinjection),
      colocalized Fos and Jun immunostaining was observed (> 90% colocalized staining
      in labeled neurons). At 4 h post-saline injection, some rats received a second
      injection of normal or hypertonic saline. A second injection of normal saline
      resulted in no Fos/Jun immunostaining 90 min later, while hypertonic saline
      induced combined Fos/Jun staining in only 17% of SON neurons. Of the remaining
      SON cells, 23% had staining to Fos alone and 4% of the cells stained for Jun
      only. In spite of the delivery of an effective second osmotic stimulus,
      determined by assessment of plasma osmolality and sodium content, SON neurons
      exhibited less colocalized Fos/Jun immunostaining, dramatically less Jun
      expression, and substantial, but attenuated, immunostaining for Fos. These
      results are discussed in the context of known negative feedback mechanisms that
      control the re-expression of these transcription factors.

PMID- 9037492
TI  - Annexin-immunoreactive proteins in the nervous system and eye of the gastropods,
      Aplysia and Helix.
AB  - We studied the distribution of annexin I- and annexin V-like proteins in the eye
      and central nervous system of the snails, Aplysia californica and Helix pomatia
      by immunocytochemistry. Annexin I-immunoreactive material in Aplysia californica
      was localized in sensory and corneal cells of the eye and in distinct neurons of
      the cerebral, buccal, and abdominal ganglia, where it was exclusively located in
      bag cells. Annexin V-immunoreactive neurons were restricted to the pleural
      ganglia of Aplysia californica. In Helix pomatia annexin I-immunoreactive neurons
      were present in the cerebral, buccal, visceral, and left and right parietal
      ganglia, whereas annexin V-immunoreactivity neurons were present in left and
      right pleural, left and right parietal, visceral, and buccal ganglia. Annexin VI
      immunoreactivity was absent in both gastropods studied. Our study shows a cell
      specific localization of annexin-like proteins in the central nervous system and
      eye of molluscs. The cell types containing the immunoreactive proteins suggests
      that the annexin-like proteins may be involved in intracellular signaling
      mechanisms, which ultimately may modulate egg-laying and circadian rhythmicity.

PMID- 9037491
TI  - Ischemic tolerance phenomenon from an approach of energy metabolism and the
      mitochondrial enzyme activity of pyruvate dehydrogenase in gerbils.
AB  - The objective of this study was to determine if the pretreatment with a sublethal
      ischemic insult, which has been shown to protect against delayed neuronal death,
      effects the recovery of energy metabolites or alters the activity of pyruvate
      dehydrogenase (PDH) following transient cerebral ischemia. Gerbils were
      pretreated with a sublethal ischemic insult, 2 min of bilateral common carotid
      artery occlusion, and 24 h later given a 5-min lethal ischemic insult. Animals
      were reperfused for 0, 10, or 60 min, or 1, 3 or 7 days. Brain metabolites, ATP,
      PCr, and lactate, and PDH activity were measured in the cortex and the
      hippocampal CA1 region. The pretreatment had no effect on ATP and PCr depletion
      or on lactate accumulation after the 5-min insult, nor on their recovery up to 1
      day reperfusion, although there was a difference in the lactate levels of the non
      pretreated and the pretreated gerbils after 10 min reperfusion. The pretreatment
      also had no effect on PDH activity during ischemia and reperfusion in either
      region. However, at 3 days reperfusion the non-pretreated animals exhibited a
      secondary decrease in ATP levels in the hippocampus. At 7 days reperfusion, ATP
      levels in the hippocampus of both the pretreated animals and the non-pretreated
      animals were significantly decreased compared to controls. Additionally, the
      level of ATP in the non-pretreated group was significantly lower than that in the
      pretreated group. The pretreatment with a sublethal ischemic insult did not
      effect the initial recovery of metabolites or the activity of PDH following
      transient cerebral ischemia. However, it protected against the secondary decrease
      of ATP levels in the hippocampus. Thus, the induction of ischemic tolerance is
      not caused by a reduction in metabolic impairment during the secondary insult.

PMID- 9037493
TI  - Cellular distribution of the rat D1B receptor in central nervous system using
      anti-receptor antisera.
AB  - Polyclonal antisera have been generated against two unique polypeptide fragments
      in the rat D1B dopamine (DA) receptor, as deduced from the cDNA sequence.
      Antisera titers were monitored using solid-phase ELISA. Once the titers were
      established, antisera specificity was determined using Chinese Hamster ovary
      (CHO) cells, stably transfected with the full-length cDNA for the rat D1B DA
      receptor. Immunoreactivity following staining with either anti-D1B DA receptor
      antisera was equivalent, selective for the D1B DA receptor-transfected CHO cells,
      and expressed at their membrane and within the cell cytoplasm. Minimal
      immunofluorescent staining for D1B DA receptor proteins was detected in
      untransfected CHO cells, or in D1A DA receptor-transfected CHO cells. The
      regional and cellular distribution patterns for the D1B DA receptor subtype were
      examined in various brain areas and illustrated significant protein levels within
      the frontal and parietal cortices and in the hippocampus and dentate gyrus.
      Lesser amounts of receptor protein staining were seen in the dorsal striatum,
      olfactory tubercle, and cerebellar vermis. D1B DA receptor protein staining was
      correlated with the cellular expression of D1B DA receptor mRNA transcripts in
      these same brain regions using concurrent fluorescent analyses. The homologous
      coincidence in staining patterns for the D1B DA receptor transcripts and encoded
      proteins in identified neurons of the frontal cortex and striatum showed
      variations in receptor expression in these identified basal ganglia pathways.

PMID- 9037494
TI  - Effects of excitatory amino acids and neuropeptide Y on the discharge activity of
      suprachiasmatic neurons in rat brain slices.
AB  - Effects of L-glutamate, AMPA, NMDA and NPY on the discharge activity of neurons
      located in the ventral subdivision of the suprachiasmatic nucleus were examined
      in submerged coronal slices of the rat hypothalamus. All substances were bath
      applied. Application of L-glutamate (14 neurons examined) induced an excitatory
      response in 8 suprachiasmatic neurons (+248.9 +/- 122.24%, mean +/- S.E.M.; P <
      0.001). A biphasic response, i.e. an initial transient excitation (+54.3 +/-
      8.21%; P < 0.001) succeeded by an inhibition (-66.2 +/- 9.31%; P < 0.001), was
      observed in 6 neurons. Application of AMPA (36 neurons examined) resulted in an
      excitation of 31 neurons (+209.2 +/- 58.58%; P < 0.0001). Application of NMDA (57
      neurons examined) induced an excitation in 34 neurons (+253.8 +/- 91.18%; P <
      0.0001), but an inhibition in 8 neurons (-757 +/- 6.52; P < 0.0001). Biphasic
      effects of NMDA with an excitatory component (+58.7 +/- 9.94%; P < 0.0001)
      succeeded by an inhibitory component (-62.0 +/- 8.07%; P < 0.0001) were observed
      in 13 neurons. In 5 of 13 examined cases, the inhibitory component of neuronal
      responses to NMDA was significantly attenuated by the simultaneous application of
      strychnine (attenuation was 56%; P < 0.05). The application of NPY (40 neurons
      examined) induced significant effects on the discharge rate of 29 suprachiasmatic
      neurons. 18 of these neurons were inhibited (-59.3 +/- 6.39%; P < 0.0001) whereas
      11 neurons were excited (+156.6 +/- 107.222%; P < 0.001) by NPY. In 8 of 11
      neurons examined, the NPY-induced inhibition was significantly attenuated by 92%
      during simultaneous application of strychnine (P < 0.001). In 23 NPY-sensitive
      neurons, the discharge activity was also affected by NMDA. Neurons excited by NPY
      were also excited by NMDA (8 cells). In neurons inhibited by NPY, application of
      NMDA induced either an inhibition (3 cells) an excitation (5 cells) or a biphasic
      effect (7 cells). Results suggest a direct excitatory effect of AMPA, NMDA and
      NPY on suprachiasmatic neurons. In contrast, inhibitory actions of NMDA and NPY
      are considered induced by an activation of inhibitory interneurons. Antagonistic
      effects of strychnine suggest an involvement of glycinergic interneurons in a
      subpopulation of neurons inhibited by NMDA and in most neurons inhibited by NPY.
      The involvement of inhibitory mechanisms in photic entrainment of the circadian
      system is discussed. An integrative model of excitatory and inhibitory actions of
      EAA and NPY on suprachiasmatic neurons is proposed.

PMID- 9037495
TI  - Progesterone treatment increases Fos-immunoreactivity within some progestin
      receptor-containing neurons in localized regions of female rat forebrain.
AB  - In female rats, the sequential release of estradiol and progesterone from the
      ovaries is required for the expression of sexual behavior during the estrous
      cycle. Many of the neuronal effects of estradiol and progesterone involve
      estrogen and progestin receptors. Treatment with a behaviorally-effective dose of
      estradiol increases Fos expression, suggestive of neuronal response, and
      subsequent treatment with a behaviorally-effective dose of progesterone further
      increases Fos expression within a few hours in female rat brain. In order to
      determine if neurons that respond to progesterone with increase Fos expression
      also contain progestin receptors, we used a double-label immunofluorescent
      technique to label both progestin receptors and Fos protein following
      progesterone or vehicle treatment of estradiol-primed female rats. As shown
      previously, progesterone treatment increased Fos expression in progestin receptor
      containing regions, such as the ventromedial nucleus of the hypothalamus and the
      medial preoptic area. In addition, progesterone treatment induced a statistically
      significant increase in Fos-immunoreactivity within progestin receptor-containing
      cells in the medial preoptic area and the ventromedial nucleus of the
      hypothalamus, but not in the arcuate nucleus. Therefore, many but not all of the
      neurons that respond to progesterone with increased Fos expression also contain
      progestin receptor-immunoreactivity. The progesterone-induced Fos expression
      within progestin receptor-containing neurons may or may not be associated with
      the effects of progesterone on sexual or other reproductive behaviors, as it
      remains to be tested. However, the Fos expression provides a useful marker to aid
      in identification of neurons that respond to a behaviorally-relevant dose of
      progesterone.

PMID- 9037496
TI  - Electron microscopic evidence for coexistence of leucine5-enkephalin and gamma
      aminobutyric acid in a subpopulation of axon terminals in the rat locus coeruleus
      region.
AB  - We recently described ultrastructural evidence for morphologically heterogeneous
      axon terminals containing the endogenous opioid peptide, methionine5-enkephalin
      (ENK), that formed synapses with neurons containing the catecholamine
      synthesizing enzyme, tyrosine hydroxylase, in the locus coeruleus (LC) of the rat
      brain. The morphological characteristics of these terminals suggested that ENK
      may be co-localized with either an excitatory or inhibitory amino acid. To
      further test this hypothesis, we combined immunogold-silver localization of gamma
      aminobutyric acid (GABA) and immunoperoxidase labeling for ENK in single sections
      through the LC, in the present study, to determine whether ENK and GABA were
      contained within single axon terminals. Light microscopic analysis of ENK and
      GABA immunoreactivities in the LC indicated that both transmitters were enriched
      in the dorsal pons. Although electron microscopy revealed that ENK and GABA were
      located primarily in axon terminals, some dendrites also contained immunolabeling
      for GABA. The dense core vesicles were consistently the most immunoreactive in
      ENK containing axon terminals and were identified toward the periphery of the
      axon terminal distal to the synaptic specialization. Axon terminals containing
      either ENK or GABA immunoreactivities contained pleomorphic vesicles as well as
      large dense core vesicles, varied in size and formed heterogeneous types of
      synaptic specializations (i.e. asymmetric vs. symmetric). Approximately 38% (n =
      76) of the axon terminals containing ENK immunoreactivity (n = 200) also
      contained GABA. Some axon terminals containing peroxidase labeling for ENK (22%;
      n = 44) converged on common targets with GABA-labeled axon terminals. Finally, a
      few ENK-labeled axon terminals (14%; n = 28) formed asymmetric (excitatory-type)
      synapses with dendrites containing gold-silver labeling for GABA. The results,
      therefore, indicate that the opioid peptide, ENK, and the inhibitory amino acid,
      GABA, may influence LC neurons by concerted actions via (1) release from a common
      axon terminal, and (2) via separate sets of afferents converging on similar
      portions of the plasmalemma of target neurons. Furthermore, these studies also
      suggest a cellular substrate for opioid inhibition of LC neurons via activation
      (i.e. asymmetric synapses) of inhibitory GABAergic neurons. Future studies are
      required to determine whether the receptive sites for ENK and GABA are located at
      similar sites on the plasma membranes of LC neurons pre- or postsynaptically and
      whether there is differential release of either transmitter from single terminals
      in the LC.

PMID- 9037497
TI  - Effects of nitric oxide synthase inhibitors on cocaine sensitization.
AB  - Behavioral sensitization to cocaine was tested for in rats pretreated with a
      nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine methyl ester (L
      NAME) or 7-nitro indazole (7-NI). A 5-day pre-exposure to once daily cocaine (15
      mg/kg, i.p.) injections yielded sensitization to cocaine (15 mg/kg)-induced
      behavioral activation. Pretreatment injections of L-NAME (100 mg/kg) or 7-NI (30
      mg/kg), administered 30 min before each cocaine pre-exposure injection, acutely
      inhibited cocaine-induced behavioral activation. No sensitization was found after
      L-NAME pretreatment in a protocol with a 3-day withdrawal between pre-exposure
      and test cocaine injections. With a 10-day withdrawal period, cocaine
      sensitization was prevented by L-NAME or 7-NI pretreatment. These results after a
      10-day withdrawal are unlikely to arise from deficient brain NO synthase activity
      on the test day. Instead, these findings suggest a role for NO in mechanisms
      underlying the development of cocaine sensitization. We conclude that NO
      participates in both the development of sensitization as well as the expression
      of cocaine-induced behavior in previously drug-naive animals.

PMID- 9037498
TI  - High extracellular glycine does not potentiate N-methyl-D-aspartate-evoked
      depolarization in vivo.
AB  - As N-methyl-D-aspartate receptor (NMDA) ionophore complexes have a distinct
      positive, allosteric regulatory site for glycine, it has been proposed that
      elevated extracellular glycine during or after cerebral ischaemia may induce
      excessive NMDA/glutamate receptor activation and, thereby, excitotoxicity. To
      test this hypothesis, we have perfused increasing concentrations of glycine,
      either alone or with co-application of NMDA, through a microdialysis probe
      implanted in the striatum of halothane anaesthetized rats. Changes in the
      extracellular field (DC) potential indicative of depolarization were recorded
      precisely at the site of drug application by an electrode incorporated within
      dialysis fibre. Microdialysis application of up to 1 mM of glycine had no effect
      on the basal DC potential. Above 10 mM, glycine produced concentration-dependent
      depolarizations, but the amplitude of these responses remained very small (e.g.
      0.52 +/- 0.05 mV for 100 mM glycine, n = 10, i.e. around 30-fold smaller than
      that of a wave of spreading depression). Application of 200 microM NMDA via the
      microdialysis probe produced consistent short-lasting depolarizations (around 2.5
      mV amplitude), but these were not potentiated by co-application of up to 100 mM
      glycine. These data do not support the view that increased extracellular
      concentrations of glycine, such as those observed in ischaemia, may be
      potentially excitotoxic. Nevertheless, as occupation of the glycine site coupled
      to the NMDA-receptor is required for NMDA/glutamate receptor activation, this
      site remains an attractive target for potential neuroprotective agents.

PMID- 9037499
TI  - Capsaicin-resistant vagal afferent fibers in the rat gastrointestinal tract:
      anatomical identification and functional integrity.
AB  - The presence and distribution of vagal fibers and terminals throughout esophagus
      and gastrointestinal tract that could be anterogradely labeled by nodose ganglion
      tracer injections was quantitatively assessed in capsaicin- and vehicle
      pretreated adult rats, in order to identify the capsaicin-resistant population.
      Up to 90% of the intraganglionic laminar endings (IGLEs), in the myenteric plexus
      of the esophagus, and 70-90% in the stomach, as well as 57% of the intramuscular
      endings or arrays (IMAs) in the fundic stomach survived the capsaicin treatment,
      while in the upper small intestine only few and in the lower small intestine, the
      cecum and colon, virtually no IGLEs survived capsaicin treatment. Intramucosal
      terminals were not assessed. Furthermore, gastric balloon distension-induced c
      Fos expression in the dorsal vagal complex was not significantly decreased in
      capsaicin-treated rats. It is concluded that among primary vagal afferents there
      is a capsaicin-resistant population that primarily innervates the esophagus and
      upper gastrointestinal tract, and a capsaicin-sensitive population that
      innervates mainly the lower tract. At least vagal gastric tension-sensitive
      afferents also seems to be functionally intact in that they may be capable of
      synaptically activating second-order neurons in the brainstem.

PMID- 9037500
TI  - Immuno-localization of serotonin 5-HT6 receptor-like material in the rat central
      nervous system.
AB  - In order to map the recently cloned serotonin 5-HT6 receptor in the rat brain and
      spinal cord, polyclonal antibodies were raised against a synthetic
      octadecapeptide corresponding to a specific portion (Leu398-Val415) of the C
      terminal domain of this receptor. Antibodies were detected by enzyme-linked
      immunosorbent assay as soon as one month after the first injection to rabbits of
      the peptide coupled to keyhole limpet hemocyanin. Immunoautoradiographic
      experiments with antibodies affinity-purified on Affi-Gel coupled to the peptide
      antigen showed that 5-HT6-like immunoreactive material was abundant in the
      olfactory tubercle (plexiform layer), cerebral cortex (frontal and entorhinal
      areas), nucleus accumbens, striatum, hippocampus (strata oriens and radiatum of
      the CA1 area, molecular layer of the dentate gyrus) and the molecular layer of
      the cerebellum. A specific immunolabeling, but at moderate intensity, was also
      observed in the thalamus, substantia nigra, superficial layer of the superior
      colliculus, motor trigeminal nucleus and facial nucleus. In contrast, no 5-HT6
      like immunoreactive material was found in white matter areas. As the regional
      distribution of 5-HT6 receptor-like immunoreactivity matched generally that
      previously found for the 5-HT6 receptor mRNA, one could infer that this receptor
      protein is addressed in the vicinity of its synthesis site, i.e. on somas and/or
      dendrites. Indeed, immunohistochemistry at the light and electron microscope
      level showed that 5-HT6-like immunoreactivity was associated with dendritic
      processes in both the striatum and the dentate gyrus of the hippocampus. The
      relative abundance of 5-HT6 receptor-like immunoreactivity in extrapyramidal and
      limbic areas suggests that 5-HT6 receptors may participate in the serotoninergic
      control of motor function and mood-dependent behavior, respectively.

PMID- 9037501
TI  - Heat shock- and ethanol-induced ionic changes in C6 rat glioma cells determined
      by NMR and fluorescence spectroscopy.
AB  - The effects of two different stressors, heat shock (HS; 44 degrees C, 20 min) and
      ethanol (1.2 M, 60 min), on ion content and membrane potential were investigated
      in C6 rat glioma cells. Both treatments were previously shown to induce the HS
      response [26]. Intracellular pH (pH(i)), sodium ion concentration ([NA+]i),
      potassium ion concentration ([K+]i) and membrane potential were determined by
      means of continuous 31P and 23Na nuclear magnetic resonance (NMR), continuous
      fluorescence spectroscopy and 86Rb uptake. Lactate extrusion was determined in
      addition with respect to pH(i) regulation. The aim of this study was a detailed
      picture of HS and ethanol-induced ion changes in a single cell type, because
      stress-induced changes in the intracellular ionic balance may be important
      factors for determining proliferation, stress response and apoptosis. HS lowered
      the pH(i) from 7.38 +/- 0.04 to about 7.05 +/- 0.04. [Na+]i decreased during HS
      to 50% of the control and recovered to normal level 95 min after HS treatment.
      During HS, [K+]i remained constant but increased after HS. The membrane potential
      hyperpolarized from -83 mV to -125 mV and returned to initial values during HS
      treatment. Lactate extrusion increased 3-fold after HS. Ethanol (1.2 M) lowered
      the pH(i) from pH 7.38 +/- 0.04 to pH 7.0 +/- 0.04, but in contrast to heat
      strongly increased [Na]i. It hyperpolarized the membrane potential from -83 to 
      125 mV. Ethanol also increased lactate extrusion similar to HS. Also in contrast
      to the effect of HS, the potassium concentration decreased during ethanol
      treatment. The Na(+)-H+ exchanger monensin was used to overcome the apparent
      inhibition of the cellular Na(+)-H+ exchanger by HS. At normal pH(e) (7.4)
      monensin increased [Na+]i and pH(i) considerably. A subsequent HS reduced [Na+]i
      only minimally. Acidification of the cells by low pH(e) (6.2) prior to HS did not
      abolish the HS-induced drop of pH(i), indicating that the Na(+)-H+ exchanger was
      also inhibited at low pH(i). At low pH(e), monensin transports H+ into the cell.
      A subsequent HS decreased pH(i) only little, showing the importance of inhibition
      of the Na(+)-H+ exchanger for the HS-induced pH(i) decrease. 100 microM amiloride
      reduced pH(i) and [Na+]i in a similar way as HS, but did not change pH(i) and
      [Na+]i much during a HS. These results indicate that some of the HS-induced ionic
      changes are mediated by inhibition of the Na(+)-H+ exchanger, activation of Na(+)
      K(+)-ATPase and changes of membrane conductance for ions.

PMID- 9037502
TI  - Infusion of quinpirole and muscimol into the ventral tegmental area inhibits fear
      potentiated startle: implications for the role of dopamine in fear expression.
AB  - Dopamine (DA) D2 and gamma-aminobutyric acid (GABA)A somatodendritic receptors
      tonically inhibit mesolimbic projection neurons in the A10 DA cell grouping of
      the ventral tegmentum. In the present study we determined the contribution of the
      ventral tegmental area (VTA) to the expression of a classically conditioned fear
      induced increase in the acoustic startle reflex. Saline applied to VTA neurons
      did not modify the capacity of a light previously associated with footshock to
      potentiate acoustic startle amplitudes; conversely, bilateral administration of
      the DA D2/3 agonist quinpirole or the GABAA receptor agonist muscimol into the
      ventral tegmentum blocked fear-potentiated startle without altering baseline
      acoustic startle responding. It was suggested that DA VTA neurons regulate the
      excitatory aspects of fear expression by gating levels of aversive emotional
      arousal within the amygdala-based fear system.

PMID- 9037503
TI  - Ultrastructural immunocytochemical localization of the dopamine D2 receptor
      within GABAergic neurons of the rat striatum.
AB  - Classical antipsychotics, which block dopamine (DA) D2 receptors, showing
      intrastriatal variation in their effectiveness in modulating GABAergic function.
      To determine the cellular basis for such differences, we examined the electron
      microscopic immunocytochemical labeling of D2 receptors and GABA in the
      dorsolateral caudate-putamen (CPn) and the nucleus accumbens (Acb) shell. In both
      regions, peroxidase reaction product and gold-silver deposits representing D2
      receptor immunoreactivity (D2-IR) and GABA immunoreactivity (GABA-IR),
      respectively, were detected in dendrites and perikarya having characteristics of
      either spiny projection neurons or aspiny interneurons. Some perikarya in both
      regions are dually labeled with D2-IR and GABA-IR. Neurons axon terminals in each
      region also contained one or both markers. However, there were notable regional
      differences in the immunolabeling patterns. In the CPn, D2-IR was more commonly
      seen in dendrites/spines than in axon terminals, and proportionally more
      dendrites were dually labeled than in the Acb. In the Acb shell, D2-IR was
      detected with similar frequency in terminals and dendrites/spines, but more
      terminals co-localized D2-IR and GABA-IR in this region compared with the CPn.
      These results provide the first ultrastructural evidence for direct D2-mediated
      effects of DA on striatal GABAergic neurons. They further suggest that modulation
      of GABAergic neurons by DA acting at D2 receptors may be relatively more
      postsynaptic in the CPn, but more presynaptic in the Acb shell.

PMID- 9037504
TI  - Glucocorticoid induced the expression of mRNA and the secretion of lipocortin 1
      in rat astrocytoma cells.
AB  - The lipocortins are a family of structurally related proteins that have been
      shown to be implicated in multiple aspects of cell biology. Subsequent research
      has shown that lipocortin 1 (LC1) participates in the physiological and
      pathological functioning of the CNS and neuroendocrine system. In the present
      study, the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA), dibutyryl
      cyclic AMP (Bt2cAMP) or dexamethasone (DEX) on expression of LC1 were
      investigated by a sandwich enzyme immunoassay and reverse transcription
      polymerase chain reaction (RT-PCR) in rat astrocytoma (C6) cells. Time-dependent
      experiments revealed that the intracellular protein content and the mRNA of rat
      LC1 increased significantly 4 h after TPA (10 mM) or DEX (1 microM) addition. TPA
      and DEX elicited a prominent induction of LC1 at 10(-8) M and 10(-6) M,
      respectively. Bt2cAMP (0.5 mM) also appeared to induce, but the induction was not
      statistically significant. In addition, DEX increased the extracellular secretion
      of LC1 without cytotoxicity. These results suggest that LC1 synthesis is
      chemically induced and selectively released from C6 cells by dexamethasone.

PMID- 9037505
TI  - Presence of catecholamines and serotonin in the rat vestibule.
AB  - The concentrations of norepinephrine (NE), dopamine (DA) and its metabolites
      DOPAC and HVA, and serotonin (5-HT) and its metabolite 5-HIAA, were quantified in
      the rat vestibule. For this purpose, homogenates of vestibules, of albino and
      pigmented rats, were analyzed using HPLC with electrochemical detection.
      Vestibules of pigmented rats showed higher DOPAC and HVA concentrations than
      those of albino rats, and male pigmented rats also showed significantly more DA
      than male albino rats. These results could indicate that the rate of DA
      metabolism in vestibules was higher in pigmented than in albino rats. The
      vestibular concentrations of NE and 5-HT did not differ significantly between the
      two strains. In contrast, 5-HIAA concentration was higher in vestibules of
      pigmented rats than in those of albino rats, suggesting an increased 5-HT
      metabolism for the former strain. Differences in monoamine concentrations between
      the two sexes o the same strain were scarce. Only, a higher HVA concentration in
      vestibules of females could indicate a higher DA metabolism.

PMID- 9037506
TI  - Early growth of regenerating neurites in acrylamide neuropathic mice: application
      of a film model.
AB  - Acrylamide intoxication markedly impairs neural regeneration following
      transection of a peripheral nerve. However, no neural inhibitory mechanism has
      yet been clarified. In the present study, the early growth of regeneration
      neurites in acrylamide neuropathic mice was analyzed using a film model:
      following transection of the common peroneal nerve, the proximal stump was
      sandwiched between two sheets of thin plastic film and kept in vivo for various
      intervals after axotomy. The regenerating axons grew for a significantly (P <
      0.01) longer distance than those in the controls up to the 2nd day after axotomy
      (day 2), but thereafter the axons showed suppressed growth. Many disoriented
      neurofilaments were already accumulated in the axons on day 1, and their number
      progressively increased. The number of neurotubules was the same as that in the
      controls on day 1, but thereafter progressively decreased, and they had almost
      disappeared by day 5. Schwann cells began to migrate from the proximal stump of
      the transected nerve on day 3, showing their strong effect in promoting the
      axonal elongation. The initial acceleration of the growth seemed to be induced by
      the unusual mass of neurofilaments, and the suppression of growth at and after
      day 3 might be the result of both the decrease in the number of neurotubules and
      a refractory state of the axons to the stimuli from the migratory Schwann cells.

PMID- 9037508
TI  - Voltage-dependent Ca2+ influx into identified leech neurones.
AB  - We determined the relationships between the intracellular free Ca2+ concentration
      ([Ca2+]i) and the membrane potential (Em) of six different neurones in the leech
      central nervous system: Retzius, 50 (Leydig), AP, AE, P, and N neurones. The
      [Ca2+]i was monitored by using iontophoretically injected fura-2. The membrane
      depolarization evoked by raising the extracellular K+ concentration ([K+]o) up to
      89 mM caused a persistent increase in [Ca2+]i, which was abolished in Ca(2+)-free
      solution indicating that it was due to Ca2+ influx. The threshold membrane
      potential that must be reached in the different types of neurones to induce a
      [Ca2+]i increase ranged between -40 and -25 mV. The different threshold
      potentials as well as differences in the relationships between [Ca2+]i and EM
      were partly due to the cell-specific generation of action potentials. In Na(+)
      free solution, the action potentials were suppressed and the [Ca2+]i/Em
      relationships were similar. The K(+)-induced [Ca2+]i increase was inhibited by
      the polyvalent cations Co2+, Ni2+, Mn2+, Cd2+, and La3+, as well as by the cyclic
      alcohol menthol. Neither the polyvalent cations nor menthol had a significant
      effect on the K(+)-induced membrane depolarization. Our results suggest that
      different leech neurones possess voltage-dependent Ca2+ channels with similar
      properties.

PMID- 9037507
TI  - Preferential adsorption, internalization and resistance to degradation of the
      major isoform of the Alzheimer's amyloid peptide, A beta 1-42, in differentiated
      PC12 cells.
AB  - A central question in Alzheimer's disease (AD) is the role of amyloid in
      pathogenesis. Recent discoveries implicating the longer A beta 1-42 form of
      amyloid in pathogenesis led us to characterize the interaction of A beta with
      cells to elucidate differences that might account for these observations. We
      characterized the adsorption, internalization and degradation of radiolabeled A
      beta in NGF-differentiated PC12 cells under conditions that are not acutely
      toxic. All A beta peptides examined absorb to the surface of PC12 cells and are
      internalized; however the adsorption and internalization of A beta 1-42 is
      significantly greater than that of A beta 1-40 and A beta 1-28. The adsorption of
      A beta 1-42 is decreased by treatment of the cells with neuraminidase, but not
      heparitinase. The fate of the internalized A beta 1-42 is also very different
      than shorter A beta peptides; a fraction of the internalized A beta 1-42
      accumulates intracellularly and is resistant to degradation for at least 3 days
      while A beta 1-40 and shorter peptides are eliminated with a half life of about 1
      h. A beta 1-42 does not appear to inhibit lysosomal hydrolases, since A beta 1-28
      is degraded at the same rate in the presence or absence of A beta 1-42. The
      intracellular A beta 1-42 is located in a dense organellar compartment and
      colocalizes with the lysosomal markers Lucifer Yellow and horseradish peroxidase.
      These data indicate that there are significant differences in the cell surface
      adsorption, internalization and catabolism of A beta 1-42 compared to A beta 1-40
      and A beta 1-28. These differences may be important for the preferential
      accumulation of the longer A beta 1-42 isoform and its association with AD
      pathogenesis.

PMID- 9037509
TI  - Vasoactive intestinal polypeptide enhances the GABAergic synaptic transmission in
      cultured hippocampal neurons.
AB  - The whole-cell mode of patch-clamp techniques was used to investigate the effect
      of vasoactive intestinal polypeptide (VIP) on spontaneous gamma-aminobutyric acid
      (GABA)-mediated inhibitory postsynaptic currents (IPSCs) of cultured hippocampal
      neurons. Application of VIP caused a significant increase in the frequency of
      spontaneous IPSCs with a reversible and dose-dependent manner. VIP had no effect
      on the mean amplitude and kinetic parameters of spontaneous IPSCs. In the
      presence of tetrodotoxin, VIP increased the frequency of miniature inhibitory
      postsynaptic currents (mIPSCs) without affecting their mean magnitude. Forskolin,
      but not its inactive analog 1,9-dideoxyforskolin, mimicked the stimulatory effect
      of VIP on spontaneous IPSCs and mIPSCs. VIP and forskolin failed to modulate
      GABAergic IPSCs in the presence of Rp-cAMPs, a cell permeable antagonist of cAMP
      dependent protein kinase (PKA). Calcium channel blocker CdCl2 did not prevent VIP
      and forskolin from increasing the frequency of mIPSCs. These results suggest that
      the activation of presynaptic VIP receptor enhances the GABAergic synaptic
      transmission in cultured hippocampal neurons through the cAMP-PKA pathway and
      that VIP is likely to increase GABA release by directly stimulating the vesicular
      release apparatus.

PMID- 9037510
TI  - Intraischemic hypothermia during pretreatment with sublethal ischemia reduces the
      induction of ischemic tolerance in the gerbil hippocampus.
AB  - We examined whether mild brain hypothermia during pretreatment with sublethal 2
      min ischemia affected the tolerance to subsequent lethal 5-min ischemia. The
      neuronal densities in the hippocampal CA1 sector of gerbils preconditioned at
      mild brain hypothermia (32% of normal) were significantly lower than those in
      gerbils preconditioned at brain normothermia (70% of normal). 72-kDa heat-shock
      protein immunoreactivity in the CA1 sector preconditioned at mild hypothermia was
      reduced. These results suggests that mild brain hypothermia during pretreatment
      with sublethal ischemia reduces the tolerance to subsequent lethal ischemia.

PMID- 9037511
TI  - Effects of acute prenatal ethanol exposure on Bergmann glia cells early postnatal
      development.
AB  - The effects of acute ethanol exposure during the prenatal phase of Bergmann glia
      cell (Bgc) generation were evaluated in three postnatal days. Ethanol exposed
      rats showed Bgc with reduced soma size, decreased number and width of their
      fibers, and increased fiber length, when compared with control animals. These
      differences, however, were significant at postnatal day 12. Our results
      demonstrate that acute, prenatal exposure to ethanol during critical stages of
      brain development disrupts Bgc early postnatal development.

PMID- 9037512
TI  - Time-dependent influence of the somatostatin analogue octreotide on the
      proliferation of rat astrocytes and glioma cells.
AB  - The somatostatin receptor subtype sst2 was visualized by immunostaining on
      cultivated rat astrocytes and C6 rat glioma cells. Octreotide, a metabolically
      stable sst2 agonist reduced [3H]thymidine incorporation into DNA of both cell
      types dose-dependently only after short-time application (2-5 h), after prolonged
      incubation (> 12 h) no antiproliferative effect was measurable. We conclude that
      sst2 receptors may be desensitized. Thus, desensitization might hinder
      application of octreotide to reduce glial tumour growth.

PMID- 9037513
TI  - Medial septal cholinergic neurons express c-Jun but do not undergo DNA
      fragmentation after fornix-fimbria transections.
AB  - We investigated the expression of inducible transcription factors (ITFs) and the
      fate of medial septal (MS) cholinergic neurons following fornix fimbria (FF)
      transection c-Jun, but not c-Fos or Krox 24 was induced in nerve growth factor
      receptor-immunoreactive (NGFr-ir), parvalbumin-negative MS neurons by 48 h and
      still highly expressed 2 months after transection. JunD was expressed only at 48
      h after transection. Levels of choline acetyl transferase immunoreactivity (ChAT
      ir) and NGFr-ir decreased substantially 7 and 14 days respectively following FF
      transection and remained depressed for up to 2 months. We also investigated other
      measures of nerve cell death and found that there was a time-dependent loss of
      cresyl violet staining, but no evidence of DNA fragmentation, acidophilia or
      clusterin expression in the MS region. There was however, good evidence of
      microglial activation and astrocyte hypertrophy in the MS. These results suggest
      that axotomized c-Jun-positive septohippocampal neurons lose their cholinergic
      phenotype but do not die for up to 2 months after FF transection. The function of
      c-Jun in axotomized MS neurons remains a mystery, but c-Jun expression alone is
      clearly not sufficient to elicit death of these neurons.

PMID- 9037514
TI  - Cationic lipid-mediated NGF gene transfection increases neurofilament
      phosphorylation.
AB  - We examined the effect of cationic lipid-mediated gene transfection of nerve
      growth factor (NGF) in primary septo-hippocampal cell cultures. Rat NGF cDNA was
      subcloned into a pUC19-based plasmid containing a CMV promoter. Two days after
      NGF gene transfection in primary cell cultures, ELISA confirmed increases in NGF
      protein secretion from transfected cells. To study the biological effect of
      cationic lipid-mediated NGF gene transfection, we analyzed the amount of
      neurofilament protein from NGF-transfected cell cultures. Western blot and
      immunohistochemical analyses detected significant increases in the phosphorylated
      form of neurofilament proteins in the cultures after cationic lipid-mediated NGF
      cDNA transfection. Cationic lipid-mediated NGF cDNA transfection did rot cause
      significant changes in the total amount of neurofilament protein. Our studies
      suggest that cationic lipid-mediated NGF gene transfection can increase
      neurofilament phosphorylation but not total neurofilament protein.

PMID- 9037515
TI  - The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic
      ischemic brain damage and repair.
AB  - The cyclic AMP-responsive element binding protein (CREB) is a basally expressed,
      post-translationally activated transcription factor that has been implicated in
      the trans-activation of a number of genes in response to cAMP and calcium
      signals. A unilateral hypoxic-ischemic (HI) injury in the 21 day old rat was used
      to examine a potential role for CREB (phosphorylated and unphosphorylated) in
      neuronal programmed cell death or cell survival. The selectively vulnerable CAI
      pyramidal cells, which undergo delayed neuronal death following mild HI, show a
      loss of CREB and phosphorylated CREB (pCREB) immunoreactivity on the injured side
      48 and 72 h following HI. In contrast the resistant dentate granule cells and
      cortical cells produce a bimodal increase in pCREB immunoreactivity, peaking 6
      and 48 h following HI. The fact that cells surviving the HI insult are showing
      increased activation of CREB suggests that this protein might be involved in the
      process of neuroprotection.

PMID- 9037516
TI  - Linkage of strain-specific nicotinic receptor alpha 7 subunit restriction
      fragment length polymorphisms with levels of alpha-bungarotoxin binding in brain.
AB  - Inbred mouse strains have been shown to differ in their levels of brain alpha
      bungarotoxin binding. These differences in alpha-bungarotoxin receptors have been
      shown to correlate with an animal's sensitivity to nicotine-induced seizures.
      Recent studies have shown that the alpha 7 nicotinic acetylcholine receptor
      subunit is the major alpha-bungarotoxin binding site in rodent brain. In this
      report, we examined whether mouse strains that differ in levels of alpha
      bungarotoxin binding and sensitivity to nicotine-induced convulsions also differ
      for the alpha 7 subunit. A full-length murine alpha 7 cDNA was cloned and
      sequenced and found to be identical to that of a mouse alpha 7 cDNA recently
      reported. Subsequently, a comparison of alpha 7 cDNA sequences and RNA species
      was performed between two strains (C3H/2 and DBA/2) that differ in levels of
      brain alpha-bungarotoxin binding and sensitivity to nicotine-induced seizures.
      The only difference observed was a single nucleotide difference in the open
      reading frame of alpha 7 that does not affect the primary amino acid sequence.
      Inbred strains were also surveyed for restriction fragment length polymorphisms
      at the alpha 7 locus. Strain-specific polymorphisms were identified, and F2 and
      backcross animals from a classic genetic cross between C3H/2 and DBA/2 mice were
      compared for the inheritance of alpha 7 genotype and alpha-bungarotoxin receptor
      levels. A significant association between genotype and receptor levels was
      observed in both, the F2 and backcross generations. These results indicate that
      alpha 7 genotype is an important determinant of alpha-bungarotoxin receptor
      levels.

PMID- 9037517
TI  - Bacterial endotoxin-induced gene expression in the choroid plexus and
      paraventricular and supraoptic hypothalamic nuclei of the sheep.
AB  - The febrile and neuroendocrine responses to circulating endotoxin are effected,
      at least in part, by a central action of prostaglandins with interleukins serving
      as intermediaries. Data from rodents suggest that prostaglandin and interleukin
      (IL-1 beta) synthesis in response to endotoxin challenge may occur within the
      circumventricular organs of the brain, especially the choroid plexus; the present
      study investigated this possibility using the sheep as an experimental model. A
      pyretic dose of bacterial endotoxin (40 micrograms lipopolysaccharide) was given
      intravenously to sheep (n = 5) and the effect on gene expression in the choroid
      plexus after a 40 min interval was compared with that observed in vehicle-treated
      animals (n = 5) using in situ hybridisation histochemistry. Evidence of
      activational and synthetic events following endotoxin administration was provided
      by significant increases in c-fos (P < 0.05) and IL-1 beta (P < 0.01) mRNA
      expression. Constitutive cyclooxygenase (cox-1 mRNA) and inducible cyclooxygenase
      (cox-2 mRNA) synthesis were unchanged. The investigation also sought to provide
      evidence for endotoxin effects on neuroendocrine activity in this species by
      examining changes in hypothalamic gene expression. The results showed that c-fos
      mRNA increased in the paraventricular (P < 0.01) and supraoptic (P < 0.05) nuclei
      and that CRH mRNA was upregulated in the paraventricular nucleus (P < 0.001).
      However, in agreement with previous work, there was no change in vasopressin gene
      expression although oxytocin mRNA was enhanced throughout the paraventricular
      nucleus (P < 0.05). These findings suggest the following: (1) possible
      involvement of the choroid plexus in the response of sheep to immunological
      challenge: (2) endotoxin-induced changes in gene expression in the ovine
      hypothalamus similar in those caused by other stressors: and (3) possible changes
      in oxytocin synthesis concomitant with fever in the sheep.

PMID- 9037518
TI  - Induction of junD mRNA after transient forebrain ischemia in the rat. Effect of
      hypothermia.
AB  - The expression of junD was studied in the rat hippocampus by in situ
      hybridization after 15 min of normothermic (37 degrees C) and hypothermic (33
      degrees C) transient forebrain ischemia. Ischemia was induced by common carotid
      artery occlusion combined with hypotension leading to damage in the CA1 region of
      the hippocampus which was prevented by hypothermia. junD mRNA was induced in the
      hippocampus within 2 h of reperfusion and was strong in the dentate gyrus but
      weak in the CA3 and CA1 subregions. Intraischemic hypothermia significantly
      augmented the junD induction in the dentate gyrus. During late reperfusion
      (between 12 and 36 h after ischemia) a transient increase in junD mRNA was seen
      in the normothermic CA3 which was abolished in the hypothermic brains. In
      contrast, in the normothermic CA1 a continuous increase of junD was seen. This
      was significantly reduced by intraischemic hypothermia. We suggest that the early
      induction in junD expression in the dentate gyrus and in the hypothermic CA3
      region is a protective reaction to the ischemic stress. The marked increase in
      resistant brain areas could be due to the preserved intracellular signaling
      pathways and a subsequent maintenance of protein synthesis. The late continuous
      increase, unique to the vulnerable normothermic CA1 region, suggests that junD
      participates in a transcriptional process that may be important for delayed
      neuronal death in the hippocampus following transient forebrain ischemia.

PMID- 9037519
TI  - Cloning of the cDNA for the human NMDA receptor NR2C subunit and its expression
      in the central nervous system and periphery.
AB  - Several overlapping cDNA clones containing 3995 nucleotides of the human 2C NMDA
      receptor subunit (NR2C) were isolated from human hippocampal and cerebellar cDNA
      libraries. The nucleic acid sequence of the overlapping cDNA clones displays 85%
      identity to that of rat NR2C. The predicted protein sequence is 1233 amino acids
      long and has 88% identity to the amino acid sequence of the rat NR2C, Northern
      blot analysis has demonstrated a wide distribution pattern of the NR2C transcript
      in the brain. While the predominant expression is in the cerebellum, as observed
      in the rat, readily detectable levels are present in the hippocampus, amygdala,
      caudate nucleus, corpus callosum, subthalamic nuclei and thalamus. NR2C was also
      detected in the heart, skeletal muscle and pancreas. Distribution of the mouse
      NR2C NMDA receptor subunit homologue was investigated in mouse brain by in situ
      hybridization histochemistry using exonic genomic probes. Expression of the
      transcript was principally in the cerebellum, but is also detected in the
      hippocampus, dentate gyrus, thalamic and subthalamic nuclei, vestibular nuclei
      and olfactory bulb. These results demonstrate a widespread expression pattern of
      the NR2C gene, both in the CNS and in the periphery.

PMID- 9037520
TI  - Differential distribution of the putative vesicular transporter for acetylcholine
      in the rat central nervous system.
AB  - The organization and distribution of the mRNA for the putative vesicular
      transporter for acetylcholine (VAChT) was studied in the rat brain by use of
      digoxigenin-labeled riboprobes and in situ hybridization technology. Signal was
      observed in all neural regions deduced to contain cholinergic somata on the basis
      of previous histochemical investigations employing choline acetyltransferase
      riboprobes and prior immunocytochemical studies with antibodies against choline
      acetyltransferase. It was absent in areas believed to contain no cholinergic
      neurons. Anti-sense riboprobes hybridized to the mRNA for the putative VAChT: (a)
      the projection neurons of the various nuclei of the basal nuclear complex, (b)
      the local circuit cells of the dorsal and ventral striata, (c) the projection
      neurons of the mesopontine complex, (d) perikarya in the ventral 2/3 of the
      medial habenula, (e) the somatic motor and autonomic cells of cranial nerves 3-7
      and 9-12, as well as perikarya in the dorsal and ventral cochlear nuclei
      presumably giving rise to efferent fibers of cranial nerve 8, and (f) the alpha
      motor and gamma-efferent motor neurons of the spinal cord. In addition, the mRNA
      for the VAChT was found in a few somata, probably ectopically located cells of
      the basal nuclear complex, in the internal capsule, central nucleus of the
      amygdala, entopeduncular nucleus, and zona incerta. It was also detected in some
      cell bodies in the reticular part of the substantia nigra, probably the rostral
      extension of the mesopontine complex, in the parabigeminal nucleus, and around
      the central canal in the spinal cord but not in cortical, hippocampal, and
      cerebellar perikarya. It is concluded that, like choline acetyltransferase, the
      mRNA for the putative acetylcholine vesicular transporter is another specific
      marker for neurons utilizing acetylcholine as a neurotransmitter. Further
      investigations of that transporter could have important implications for various
      diseases involving cholinergic systems, such as Alzheimer's disease.

PMID- 9037521
TI  - A new quantitative solution hybridisation-RNase protection assay for APP and
      APLP2 mRNA.
AB  - Amyloid precursor protein (APP) and amyloid precursor-like protein 2 (APLP2) are
      members of a multigene family of proteins implicated in the pathogenesis of
      Alzheimer's disease. We describe the development of an RNA-RNA solution
      hybridisation-RNase protection assay to quantify APP mRNA. APP mRNA splice forms
      containing the Kunitz-type protease inhibitor (KPI) insert, and APLP2 mRNA in
      total nucleic acid extracts from a range of tissue types. Solution hybridisation
      RNase protection assay enables absolute quantification of target mRNA, by
      conversion of the hybridisation signal to pg mRNA using a standard curve. The
      assay is sensitive, capable of detecting 1 pg target mRNA, and reproducible, with
      an inter-assay variability of less than 10% and an intra-assay variability of 3
      4%. We quantified APP and APLP2 mRNA in cell lines and post-mortem human brain
      tissue samples. To test whether we could detect physiological differences in APP
      mRNA levels, a fibroblast cell line with a paternal chromosome 21 deletion of the
      region including the APP gene was analysed and found to express half as much APP
      mRNA as control fibroblasts. In addition, a reversible, approx. 30% increase in
      APP mRNA levels was detected in human lymphoblastoid cell lines following heat
      shock, a physical stimulus previously shown to increase APP expression. Regional
      differences in the expression of APP and APLP2 were seen in human post-mortem
      cerebral cortex and cerebellum. Levels of APP and APLP2 mRNA were highest in the
      temporal cortex, slightly lower in frontal and occipital cortices, and lowest in
      the cerebellum. The highest proportion of KPI-containing APP was seen in the
      frontal and temporal cortices. The ratio of APP:APLP2 mRNA was 1:0.3 in the
      cortical tissue and 1:0.8 in the cerebellum. In conclusion, quantitative solution
      hybridisation-RNase protection assay of total APP. APP KPI and APLP2 mRNA
      provides a new tool to improve the resolution of studies of potentially subtle
      alterations in the expression of these genes in both cell culture model systems
      and Alzheimer's disease post-mortem human brain tissue.

PMID- 9037522
TI  - Quantification of APP and APLP2 mRNA in APOE genotyped Alzheimer's disease
      brains.
AB  - Amyloid precursor protein (APP) is metabolised to produce A beta, a peptide found
      aggregated in Alzheimer's disease neuritic plaques. APP is a member of a
      multigene protein family which includes amyloid precursor-like protein 2 (APLP2).
      Since A beta accumulation can be triggered by factors acting up- or downstream of
      APP processing, we investigated whether APP mRNA expression was altered in
      Alzheimer's disease post-mortem cerebral cortex. In addition, we characterised
      cortical APLP2 mRNA levels. Quantitative RNA-RNA solution hybridisation-RNase
      protection was used to assay total APP. APP containing the Kunitz-type protease
      inhibitor (KPI) insert and APLP2 mRNA in mid-temporal and superior frontal
      cortices from apolipoprotein E-genotyped subjects with Alzheimer's disease, other
      neurological diseases and non-demented controls. Approximately 3 times more APP
      than APLP2 mRNA was detected and about 70% of total APP mRNA contained the KPI
      insert in the control subjects. Total APP and APLP2 mRNA levels were
      significantly reduced in Alzheimer's disease mid-temporal, but not superior
      frontal cortex, suggesting that regional reductions in these mRNA correlate with
      severity of disease pathology. A small significant increase in the proportion of
      APP KPI mRNA was seen in both cortical regions in Alzheimer's disease.
      Apolipoprotein E genotype did not influence cortical levels of total APP, APP KPI
      or APLP2 mRNA. Alzheimer's disease-related increases in tissue DNA content were
      seen in both regions studied, while tissue RNA levels were reduced in the
      positive disease controls. In summary, these results indicate that Alzheimer's
      disease is not associated with over-expression of either APP or APLP2 mRNA. Our
      findings reveal a disease-associated increase in the proportion of APP KPI
      containing isoforms, and further investigation should clarify whether this
      predisposes affected individuals to A beta production and aggregation, or
      reflects later events such as gliosis and neuronal cell death.

PMID- 9037523
TI  - Identification and characterization of an endogenous ligand for opioid receptor
      homologue ROR-C: its involvement in allodynic response to innocuous stimulus.
AB  - We reported here purification and characterization of a novel heptadecapeptide in
      bovine brain as an endogenous ligand for ROR-C, an opioid receptor homologue
      cloned from rat cerebrum. The amino acid sequence of the peptide that we purified
      is identical to those recently identified as nociceptin in rat brain and orphanin
      FQ in porcine brain. The peptide inhibited the forskolin-induced cyclic AMP
      accumulation in ROR-C expressing Chinese hamster ovary cells. Studies on
      inhibitory activity of cyclic AMP accumulation and Northern blot analysis showed
      that the peptide and its precursor mRNA are present in a number of brain regions,
      less abundant in the spina cord, and negligible in the cerebellum. In situ
      hybridization analysis revealed that hybridization-positive neurons were
      distributed in the superficial layer (lamina I) of the dorsal horn and were also
      interspersed between the tract of Lissauer in the spinal cord. Intrathecal
      administration of the peptide into conscious mice induced allodynia, a pain
      response to innocuous tactile stimuli, in a beli-shaped manner. These results
      demonstrate that the peptide exists in the brain and spinal cord and plays an
      important role in pain transmission.

PMID- 9037524
TI  - Altered expression of group I metabotropic glutamate receptors in the hippocampus
      of amygdala-kindled rats.
AB  - Kindling is a well documented model of acquired focal epilepsy and synaptic
      plasticity in the nervous system. Previous biochemical studies have indicated an
      increase in mGluR-mediated phosphoinositide hydrolysis in the amygdala or
      hippocampus of fully kindled animals. In this study we have used in situ
      hybridisation techniques to examine the mRNA expression of group I metabotropic
      glutamate receptors (mGluR1 and mGluR5 both linked to phosphoinositide
      hydrolysis) in the hippocampus of amygdala-kindled animals sacrificed 24 h, 7
      days or 28 days following the last electrically evoked stage 5 seizure, and in
      implanted non-stimulated control rats. Results indicate an initial up-regulation
      in mGluR1 mRNA (expressed as percentage of control) bilaterally in the DG (35
      40%) and CA3 (16-48%), and unilaterally in CA4 (12%) in the 24 h post-kindled
      group. In kindled animals studied 7 days after the last seizure, these changes
      were either reduced or had returned to control levels. By 28 days mGluR1 mRNA
      levels had returned to control levels, with only a persistent increase in
      expression unilaterally in the DG (14%). In contrast, an initial down-regulation
      in mGluR5 mRNA was observed bilaterally in CA4 (-45 and -25%) and CA1 (-46 and 
      45%), and unilaterally in DG and CA3 (-27 and -42% respectively) 24 h after the
      last kindled seizure. In the 7 and 28 day kindled groups significant alterations
      in expression of mGluR5 mRNA were still apparent. These data show that the mRNAs
      for mGluR1 and mGluR5 are differentially regulated by kindling, indicating that
      the expression of each of these receptors is under independent regulatory
      control. These perturbations in mRNA expression may contribute to kindling
      epileptogenesis but are unlikely to account for the maintenance of the kindled
      state.

PMID- 9037525
TI  - Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs.
AB  - The expression of sodium channel alpha-, beta 1- and beta 2-subunit mRNAs was
      examined in adult rat DRG neurons in dissociated culture at 1 day in vitro and
      within sections of intact ganglia by in situ hybridization and reverse
      transcription polymerase chain reaction (RT-PCR). The results demonstrate that
      sodium channel alpha-subunit mRNAs are differentially expressed in small (< 25
      microns diam), medium (25-45 microns diam.) and large (> 45 microns diam.)
      cultured DRG neurons at 1 day in vitro (div). Sodium channel mRNA I is expressed
      at higher levels in large neurons than small DRG neurons, while sodium channel
      mRNA II is variably expressed, with most cells lacking or exhibiting low levels
      of detectable signal of these mRNAs and limited numbers of neurons with moderate
      expression levels. DRG neurons generally exhibit negligible or low levels of
      hybridization signal for sodium channel mRNA III. Sodium channel mRNAs Na6 and
      NaG show similar patterns of expression, with most large and many medium DRG
      neurons exhibiting high levels of expression. The mRNA for the rat cognate of
      human sodium channel hNE-Na is detected in virtually every DRG neuron; most cells
      in all size classes exhibit moderate or high levels of hNE-Na expression. Sodium
      channel SNS mRNA is expressed in all size classes of DRG neurons, but shows
      greater expression in small and medium DRG neurons than in large neurons. The
      mRNA for the rat cognate of mouse sodium channel mNa 2.3 is not detected, or is
      detected at low levels, in most DRG neurons, regardless of size, although
      moderate expression is detected in some neurons. Sodium channel beta 1- and beta
      2-subunit mRNAs exhibit similar expression patterns; they are detected in most
      DRG neurons, although the level of expression tends to be greater in large
      neurons than in small neurons. RT-PCR and in situ hybridization of intact adult
      DRG showed a similar pattern of expression of sodium channel mRNAs to that
      observed in DRG neurons in vitro. These results demonstrate that adult DRG
      neurons express multiple sodium channel mRNAs in vitro and in situ and suggest a
      molecular basis for the biophysical heterogeneity of sodium currents observed in
      these cells.

PMID- 9037526
TI  - Chronic triazolam and its withdrawal alters GABAA receptor subunit mRNA levels:
      an in situ hybridization study.
AB  - The benzodiazepine (BZ), triazolam (TRZ), results in tolerance and physical
      dependence. We performed in situ hybridization (ISH) experiments to gain a more
      complete understanding of the processes involved in mediating the effects of
      chronic TRZ ISH allowed us to determine whether GABAA receptor subunit mRNAs are
      affected by 4 weeks of TRZ administration and its withdrawal and to localize the
      changes to discrete brain regions. Using oligonucleotide probes directed toward
      the alpha 1-6, beta 1-3, and delta subunit mRNAs, we analyzed message density in
      63 brain regions of TRZ-treated and control rat brains, alpha 1-4, beta 1-3, and
      delta subunit mRNA levels were altered by 28 days of chronic TRZ. No changes were
      noted in alpha 5-6 mRNA levels. Many of the changes measured were localized to
      neural structures within the limbic circuit of Papez, or in close communication
      with this pathway. After a 24 h withdrawal period from 4 weeks of TRZ treatment,
      the changes noted on the 28th day of treatment were reversed. Moreover, brain
      regions that were unaffected by the 4-week treatment were altered by the 24 h
      withdrawal. Our results indicate that chronic treatment and withdrawal are
      associated with separate processes and that chronic TRZ is correlated with limbic
      alterations which may be responsible for some of its chronic effects.

PMID- 9037527
TI  - mRNAS for one, two or three members of trk receptor family are expressed in
      single rat trigeminal ganglion neurons.
AB  - We studied the expression of mRNAs of neurotrophin (NTF) receptors trkA, trkB and
      trkC in single rat trigeminal ganglion neurons at embryonic days 12 and 16 to
      determine, whether single trigeminal ganglion neurons express one trk family
      member or coexpress several of them. For that purpose we elaborated a sensitive
      technique of reverse transcriptase-polymerase chain reaction to detect all
      neurotrophin receptors in a single neuron. Expression of neurofilament light
      chain mRNA was used as a positive marker to confirm the recovery of mRNAs from
      single neurons. Neurofilament-positive samples were subsequently analyzed for the
      expression of mRNAs for catalytic trkA, trkB, and trkC, and in some cases, low
      affinity neurotrophin receptor (p75). We found neurons expressing one,
      coexpressing two, or even all three trk receptors. In many neurons analyzed, p75
      mRNA was coexpressed with trks, but we also found neurons expressing only trks
      without p75, and a neuron expressing p75 alone. There were also neurons
      containing neither trk receptors nor p75. We provide here first direct evidence
      that single sensory neurons can simultaneously express three or even four
      neurotrophin receptors.

PMID- 9037528
TI  - Expression of NGFI-B mRNA in a rat focal cerebral ischemia-reperfusion model.
AB  - Cerebral ischemia is known to induce the expression of several immediate early
      genes (IEGs), including c-fos and c-jun, which subsequently regulate a number of
      late effector genes. In this study, we examined the expression of NGFI-B (or nur
      77) mRNA in a rat focal cerebral ischemia-reperfusion model. NGFI-B is a member
      of the IEGs which encodes for a nuclear receptor and is rapidly induced by nerve
      growth factor (NGF). Northern blot analysis showed a rapid but transient
      enhancement of NGFI-B mRNA, a peak level for which was observed at 30 min of
      reperfusion following 60 min ischemic insult. At the peak level, quantitative
      analysis of the blot indicated a 12-fold and 4-fold increase of NGFI-B mRNA in
      the ischemic cortex and ipsilateral hippocampus, respectively, as compared to the
      sham-operated control. No apparent changes in mRNA levels were observed within
      contralateral sites of the cortex. Results from in situ hybridization showed that
      severe ischemia (60 min) resulted in a marked increase of NGFI-B mRNA throughout
      the entire ischemic cerebral cortex. The increase was particularly notable in the
      frontal, occipital, perirhinal and piriform cortical regions and in the dentate
      gyrus and CAI-3 regions of the ipsilateral hippocampus. A marked induction was
      also noted in the ipsilateral caudate putamen. Unlike the induction profile of
      NGFI-B mRNA, severe ischemia resulted in bilateral increases of its family gene,
      NGFI-A mRNA. The spatial induction profile is similar to that of NGFI-B mRNA in
      both hemispheres, except within the region of the contralateral dentate gyrus
      which showed low levels of NGFI-A mRNA. The expression pattern of NGF and BDNF
      mRNA, upstream genes of NGFI-B, were also examined. Interestingly the temporal
      and spatial expression patterns of BDNF mRNA were very similar to that of NGFI-A
      mRNA under the same conditions, whereas increased NGF and NGFI-B mRNA were
      observed only in the ipsilateral hemisphere. It is likely that multiple and/or
      overlapping pathways are activated subsequent to ischemic challenge which in turn
      are crucial for cel survival and/or functional recovery following focal cerebral
      ischemia.

PMID- 9037529
TI  - Brain substrates activated by electroacupuncture of different frequencies (I):
      Comparative study on the expression of oncogene c-fos and genes coding for three
      opioid peptides.
AB  - Low and high frequency electroacupuncture (EA)-produced analgesia have been shown
      to be mediated by different brain substrates and different opioid peptides. In
      this study, Fos-like immunoreactivity (FLI) and in situ hybridization of the
      three opioid mRNAs were used to examine the effect of low (2 Hz) and high (100
      Hz) frequency EA on neuronal activities, and the expression of opioid genes. 2 Hz
      and 100 Hz EA induced a markedly different spatial patterns of Fos expression in
      the rat brain, suggesting there are distinct neuronal pathways underlying EA of
      different frequencies. Likewise, 2 Hz and 100 Hz EA exert differential effects on
      opioid gene expression: while 2 Hz EA induced a more extensive and intensive
      preproenkephalin (PPE) mRNA expression than 100 Hz EA, it had no effect on
      preprodynorphin (PPD) mRNA expression which was significantly increased by 100 Hz
      EA stimulation. In contrast, EA of both frequencies did not affect POMC mRNA
      expression.

PMID- 9037530
TI  - Brain substrates activated by electroacupuncture (EA) of different frequencies
      (II): Role of Fos/Jun proteins in EA-induced transcription of preproenkephalin
      and preprodynorphin genes.
AB  - Antisense oligodeoxynucleotides (ODNs) of c-fos and/or c-jun were used in this
      study to investigate the role of Fos and Jun proteins in electroacupuncture (EA)
      induced transcription of the opioid genes, preproenkephalin (PPE),
      preprodynorphin (PPD) and proopiomelanocortin (POMC). As the results showed, EA
      induced Fos and fun expression was blocked efficiently and specifically by e-fos
      and c-jun antisense ODNs, respectively. This treatment significantly prevented EA
      induced PPD, but not PPE, mRNA expression. These results suggest that Fos and Jun
      proteins are involved in PPD rather than PPE gene transcription activated by EA
      stimulation.

PMID- 9037531
TI  - Brain specific proteins binding to the 3' UTR of the 5-HT2C receptor mRNA.
AB  - The 5-HT2C receptor2 is a prominent serotonin receptor that is uniquely expressed
      in the central nervous system and has been implicated in a variety of psychiatric
      diseases. While characterizing the 5-HT2C receptor gene, we observed that the
      mRNA contains a long 3' untranslated region that binds multiple brain proteins.
      Two proteins, molecular weights 55 and 58 kDa, were of particular interest
      because they were detected only in brain regions known to express the 5-HT2C
      receptor abundantly, namely, the hippocampus and cortex. These proteins bind with
      high affinity to the 5-HT2C receptor mRNA at its extreme 3' end (Kd = 1.8 nM),
      and binding can be specifically competed by selected regions of the 3' UTR.
      Furthermore, binding of the 55 and 58 kDa proteins to the mRNA is directionally
      specific and shows preference for an AU-rich loop containing 6 to 7 nucleotides.
      These results suggest the possibility that these two brain specific proteins may
      play a role in the post-transcriptional regulation of the 5-HT2C receptor, and
      that post-transcriptional control of 5-HT2C receptor expression may be an
      important regulatory mechanism which has not been previously reported for this
      serotonin receptor subtype.

PMID- 9037532
TI  - Cloning and expression of the mouse serotonin transporter.
AB  - A mouse brain cDNA encoding the high-affinity serotonin transporter (SERT) has
      been identified and characterized. The mouse transporter sequence (mSERT) encodes
      a protein of 630 amino acids which contains twelve potential transmembrane
      domains (TMDs), N-linked glycosylation and kinase-mediated phosphorylation sites,
      and high levels of homology with rat and human SERTs. Heterologous expression of
      mSERT in COS-I cells resulted in a [3H]serotonin transport activity characterized
      by kinetic saturability (Km = 403 +/- 42 nM. Vmax = 1.02 +/- 0.10 pmol/mg/min),
      Na1 and Cl- dependences (5HT:Na+:Cl- coupling ratio of 1:1:1), and sensitivity to
      known inhibitors of serotonin transport (including antidepressant and
      psychostimulant agents). Northern analysis using mSERT cDNA as probe revealed a
      single 3.4 kb mRNA species expressed in mouse lung, midbrain and brainstem
      regions, and absent from heart and liver. In situ hybridization studies further
      established the specific localization of mSERT gene expression to the raphe
      nuclei of the mouse midbrain. The identified mSERT cDNA sequence provides a new
      tool for the evaluation of serotonin transport pharmacology in heterologous
      expression systems and provides an opportunity for the evaluation of mSERT gene
      expression in a well-characterized model of mammalian development.

PMID- 9037533
TI  - Carbachol stimulates c-fos expression and proliferation in oligodendrocyte
      progenitors.
AB  - To determine if muscarinic receptor-activation plays a role in oligodendrocyte
      development, the effect of carbachol a stable acetylcholine analog, on gene
      expression and proliferation was investigated. Using Northern blot analysis we
      showed that carbachol caused a time and concentration-dependent increase in c-fos
      mRNA. This effect was blocked by atropine, a non-selective muscarinic antagonist.
      In addition, the muscarinic-stimulated c-fos increase was inhibited by 1-(5
      isoquinoline-sulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein
      kinase C (PKC), but not by N-2-(p-bromocinnamylamino)-ethyl-5-isoquinoline
      sulfonamide (H-89), a potent inhibitor of protein kinase A, suggesting the
      involvement of PKC in mediating the response. Down-regulation of PKC by overnight
      pre-treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) blocked only the
      phorbol ester-stimulated c-fos accumulation while no effect was observed in the
      carbachol-induced response. These results suggested that carbachol stimulated an
      H-7 sensitive PKC pathway which may be different than that activated by TPA.
      Further evidence for two separate mechanisms of proto-oncogene induction was
      provided by the additive effect of carbachol and TPA. Induction of c-fos mRNA by
      carbachol was dependent on both influx of extracellular Ca2+ and release from
      intracellular stores, as both EDTA and BAPTA blocked the response. Since
      activation of muscarinic receptors can affect cell division in other cellular
      systems, the effect of carbachol on [3H]thymidine and bromodeoxyuridine
      incorporation into oligodendrocyte DNA was measured. Carbachol stimulated DNA
      synthesis in oligodendrocyte progenitors. This effect was mediated by muscarinic
      receptors as [3H]thymidine incorporation was prevented or significantly reduced
      by the addition of atropine. In conclusion, the present findings suggest that,
      the neurotransmitter, acetylcholine may act as a trophic factor in developing
      oligodendrocytes, regulating their growth and development in the central nervous
      system.

PMID- 9037534
TI  - Regulation of galanin gene expression in the hypothalamic paraventricular nucleus
      of the obese Zucker rat by manipulation of dietary macronutrients.
AB  - Lean and obese male Zucker rats were fed high fat (72% of energy as fat), high
      carbohydrate (66% of energy as carbohydrate) or intermediate diets for 4 weeks
      commencing 1 week after weaning. We examined the effects of these diets on growth
      rates, plasma insulin and corticosterone titres, and hypothalamic gene expression
      of 3 appetite-related neuropeptides. Messenger RNA levels for neuropeptide Y
      (NPY), galanin (GAL) and corticotropin-releasing factor (CRF) in critical
      hypothalamic locations were measured by in situ hybridization in each brain.
      Obese rats grew more rapidly and had elevated plasma insulin and corticosterone
      concentrations relative to their lean littermates. The obese phenotype was also
      associated with elevated NPY gene expression in the arcuate nucleus of the
      hypothalamus and increased GAL gene expression in the hypothalamic
      paraventricular nucleus. There was no effect of diet on NPY or CRF gene
      expression in either lean or obese rats. However, maintenance on the high fat
      diet had a significant effect on GAL gene expression in obese but not lean rats:
      high fat diet significantly reduced mRNA levels in the obese rats. This reduction
      in GAL mRNA was accompanied by attenuation of the hyperinsulinemia that is
      characteristic of this genetic obesity.

PMID- 9037535
TI  - Molecular regulation of the brain interleukin-1 beta system in obese (fa/fa) and
      lean (Fa/Fa) Zucker rats.
AB  - Interleukin-1 beta (IL-1 beta) induces anorexia when administered acutely or
      chronically into the cerebrospinal fluid (CSF) at doses that yield estimated
      pathophysiological concentrations. Enhanced sensitivity to IL-1 beta-induced
      anorexia has been observed in animal models of obesity, including the obese
      (fa/fa) Zucker rat. Obesity is also associated with increased tumor necrosis
      factor-alpha mRNA expression in adipose tissue. This suggests that obese
      individuals may have dissimilar sensitivity to cytokine action and differential
      regulation of cytokine production. In this study, we investigated the regulation
      of the IL-1 beta system (IL-1 beta, IL-1 receptor type I (IL-1RI) and IL-1
      receptor antagonist (IL-1Ra)) in the central nervous system (CNS) in response to
      the chronic intracerebroventricular (i.c.v.) microinfusion (via osmotic
      minipumps) of 8 ng IL-1 beta/24 h/72 h-a dose that yields estimated
      pathophysiological concentrations in the CSF. IL-1 beta, IL-1RI and IL-1Ra mRNAs
      were determined by sensitive RNase protection assays in brain target regions for
      IL-1 beta (cerebellum, parieto-frontal cortex, hippocampus, hypothalamus and
      midbrain). The results show that chronic i.c.v. microinfusion of IL-1 beta
      increased the IL-1 beta mRNA, IL-1R1 mRNA and IL-1Ra mRNA levels in the
      hypothalamus > cerebellum in both obese (fa/fa) and lean (Fa/Fa) Zucker rats. IL
      1 beta mRNA levels also increased in the cortex, hippocampus and midbrain of
      obese (fa/fa) rats. The profiles of IL-1 beta mRNA, IL-1RI mRNA and IL-1Ra mRNA
      in the same hypothalamic samples obtained from obese or lean rats were highly
      intercorrelated. However, no significant differences in the level of IL-1 beta
      system mRNAs induction were observed in any brain region between obese and lean
      rats. On the other hand, levels of rat glyceraldehyde 3-phosphate dehydrogenase
      mRNA were fairly constant, and heat-inactivated IL-1 beta (8 ng/24 h/72 h) had no
      effect on IL-1 beta, IL-1RI and IL-1Ra mRNAs levels in any brain region. The data
      suggest: (1) the operation of an IL-1 beta feedback system (IL-1 beta/IL-1Ra/IL
      1RI) in brain regions; (2) that enhanced sensitivity of obese rats to IL-1 beta
      induced anorexia is not dependent on changes in the brain IL-1 beta system at the
      mRNA level; and (3) that the present novel approach can be used to investigate
      the molecular basis of cytokine action in the CNS.

PMID- 9037536
TI  - Repeated injections of dizocilpine maleate (MK-801) do not suppress the effects
      of nigrostriatal dopamine deafferentation on glutamate decarboxylase (GAD67) mRNA
      expression in the adult rat striatum.
AB  - The present study examined the effects of glutamate transmission blockade through
      N-methyl-D-aspartate (NMDA) receptor subtype by repeated administration of
      dizocilpine maleate (0.2 mg/kg. i.p., twice a day for eight days) alone or in
      combination with unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal
      dopaminergic pathway on GABAergic neurons in the adult rat striatum. For this
      purpose, the expression of the messenger RNA encoding for the 67 kDa isoform of
      the GABA synthesizing enzyme, glutamate decarboxylase (GAD67 mRNA), was studied
      in the various conditions by quantitative in situ hybridization. The dizocilpine
      maleate treatment alone did not induce significant change of GAD67 mRNA levels in
      the striatum, indicating that NMDA receptors may not have a major role in the
      transcriptional regulation of GAD67 in the adult rat striatum. As reported
      previously, the unilateral dopaminergic lesion resulted in marked increases in
      GAD67 mRNA levels in the ipsilateral striatum. This up-regulation was not
      significantly affected by the treatment with dizocilpine maleate started 12 days
      after the unilateral intranigral 6-hydroxydopamine injection. Therefore, NMDA
      receptors are unlikely to contribute to the dopamine lesion-induced GAD67 mRNA up
      regulation in striatal projection neurons. This result is of major interest in
      comparison with our previous finding that NMDA receptor activation is necessary
      to maintain the up-regulation of enkephalin expression in the striatum after
      dopamine lesion.

PMID- 9037537
TI  - Cocaethylene stimulates the secretion of ACTH and corticosterone and the
      transcriptional activation of hypothalamic NGFI-B.
AB  - Cocaethylene is an active cocaine metabolite formed by hepatic carboxylesterases
      in the presence of alcohol. The effects of cocaethylene on the hypothalamic
      pituitary-adrenal (HPA) axis were investigated in vivo using adrenocorticotropic
      hormone (ACTH) and corticosterone secretion as indices of peripheral stimulation.
      To ascertain the central effects of cocaethylene on discrete neurons of the
      paraventricular nucleus (PVN) of the hypothalamus, a specific cRNA probe was used
      to follow changes in the transcriptional activation of nerve growth factor I-B
      (NGFI-B), a member of the family of immediate-early genes. Intravenous (i.v.)
      injection of cocaethylene (16 mumol/kg) to rats produced a marked but transient
      increase in plasma levels of ACTH and corticosterone within 10 min of drug
      exposure. Secretion of these hormones was accompanied by elevated levels of NGFI
      B mRNA detected 30 min after i.v. or intraperitoneal (i.p., 60 mumol/kg)
      cocaethylene administration. The transcriptional stimulation of this immediate
      early gene within parvocellular secretory neurons was relatively brief in
      duration, returning to basal levels by 180 min after drug exposure. As expected
      both routes of cocaethylene administration produced an increase in locomotor
      activity compared to saline-vehicle rats, with no differences between i.v. or
      i.p. routes with respect to duration of behavioral activation. Taken together,
      these findings indicate that cocaethylene has neuroendocrine properties on its
      own, targeting a critical region of the brain that regulates stressful events in
      the body. This, combined with other neurochemical properties, points to the
      possibility of cocaethylene augmenting the effects of a drug-dependent state.

PMID- 9037538
TI  - Alterations in mRNA expression of systems that regulate neurotransmitter synaptic
      content in seizure-naive genetically epilepsy-prone rat (GEPR): transporter
      proteins and rate-limiting synthesizing enzymes for norepinephrine, dopamine and
      serotonin.
AB  - Two models of genetically epilepsy-prone rat (GEPR) exist, the GEPR-3 and GEPR-9,
      GEPR-3 and GEPR-9 share a deficiency in presynaptic norepinephrine (NE) and
      serotonin (5HT) content in specific regions of the central nervous system (CNS).
      The presynaptic content of dopamine (DA) does not appear to be altered in either
      adult GEPR strain compared to Sprague-Dawley (SD) rats, the strain from which the
      GEPR was derived. Presynaptic content of monoamine neurotransmitters, such as NE,
      5HT and DA, are maintained by several regulatory proteins which include:
      synthesis, re-uptake, release, degradation and vesicular transport. To further
      characterize the monoamine deficiency observed in the GEPR, the mRNA level of the
      rate limiting enzymes for the synthesis of NE, 5HT and DA and each of the
      neurotransporter proteins were measured in seizure-naive GEPR-3, GEPR-9 and SD
      rats. In the locus coeruleus (LC), the major noradrenergic locus, tyrosine
      hydroxylase (TH) mRNA level was significantly reduced only in GEPR-9 animals
      compared to SD rats and GEPR-3, while NE transporter (NET) mRNA was significantly
      elevated in GEPR-3 compared to SD rats and GEPR-9. TH and DA transporter (DAT)
      mRNA was measured in the dopaminergic neurons of the substantia nigra pars
      compacta (SNpc), ventral tegmental area (VTA) and zona incerta (ZI), DAT mRNA
      level was significantly reduced in all dopaminergic neurons in the GEPR-3
      compared to SD rats and GEPR-9, while TH mRNA level was significantly elevated in
      the SNpc/VTA equally in GEPR-3 and GEPR-9 compared to SD rats. In the ZI, TH mRNA
      level was significantly reduced in GEPR-3 compared to SD rats and GEPR-9. In the
      dorsal raphe (DR), a major serotonergic locus, tryptophan hydroxylase (TRH) mRNA
      level was not significantly different from SD in either strain of GEPR; however,
      5HT transporter (SERT) mRNA level was significantly reduced in GEPR-9 in the
      dorsal and lateral regions of the DR compared in SD rats and GEPR-3. These data
      indicate that two of the regulatory systems that maintain NE, 5HT and DA content
      are altered in a differential manner in seizure-naive GEPR-3 compared to seizure
      naive GEPR-9, with GEPR-3 showing more alterations in dopaminergic neurons. It is
      uncertain at the present time how these alterations in mRNA level relate to the
      enhanced seizure susceptibility of these animals. It was apparent that a
      straightforward correlation between neurotransmitter loss to transcriptional
      changes in synthesizing enzymes mRNA or to re-uptake protein mRNA was not
      observed in noradrenergic and serotonergic neurons. Therefore, the decrease in
      presynaptic NE and 5HT tissue content in these animals may be due to
      posttranscriptional modification. In contrast, presynaptic DA tissue content
      which was unaltered in both strains of GEPR, shows an alteration in TH and DAT
      mRNA level compared to SD rats in all dopaminergic neurons examined. This
      indicates a possible involvement of DA in regulating the seizure susceptibility
      of these animals.

PMID- 9037539
TI  - Role of actin in the organisation of brain postsynaptic densities.
AB  - Brain synaptic junctions are marked by a prominent dense-staining structure, the
      postsynaptic density (PSD), embedded in the postsynaptic membrane. Isolated PSDs
      contain a complex mixture of proteins among which the most abundant are the alpha
      subunit of calcium/calmodulin-dependent kinase II (CaMK II alpha) the membrane
      cytoskeletal proteins actin and spectrin and receptors for both excitatory and
      inhibitory neurotransmitters. We have investigated the relationship of these
      proteins to the junctional structure by extracting isolated PSDs with lithium
      diiodosalicylate (LIS). This selectively solubilized actin and spectrin while
      other prominent PSD proteins, such as CaMK II alpha, the AMPA- and NMDA-type
      glutamate receptors and GABA receptors, were not extracted at all. Electron
      microscopy revealed that LIS treatment caused some fragmentation of PSDs but that
      their basic lattice-like structure remained intact. These observations suggest
      that PSD structure is organised at two levels; a core component containing CaMK
      II alpha and neurotransmitter receptors which we have previously described as the
      postsynaptic junctional lattice and a peripheral actin-associated component that
      draws the lattice components together into the complete PSD structure.

PMID- 9037541
TI  - Cloning and expression localization of cDNA for rat homolog of TRP protein, a
      possible store-operated calcium (Ca2+) channel.
AB  - A 3.2 kbp cDNA clone encoding a possible candidate for the store-operated Ca2+
      channel was isolated from a rat brain cDNA library. The deduced amino acid
      sequence was 51.8% identical to TRP encoded by a Drosophila trp (transient
      receptor potential) gene and contained ankyrin motifs, a coiled-coil structure
      and six transmembrane segments similar to the previously identified TRP family
      and named as TRP-R (rat TRP). By in situ hybridization histochemistry of rat body
      on embryonic day 15, no significant expression signal for TRP-R was detected. On
      embryonic day 20 and postnatal day 1, the expression signals were most evident in
      the septum, cerebral cortical plate and hippocampal neuronal layers. On postnatal
      day 7 and thereafter the expression in the cerebral cortex and the septum
      decreased progressively, and weak expression remained only in the CA1 and CA2
      neuronal layers of the hippocampus in the brain on postnatal day 21 and 49. This
      limited spatiotemporal expression of this novel molecule. TRP-R, suggests that it
      is involved in some specific functions related to the neuronal differentiation.

PMID- 9037540
TI  - Long-term treatment with the tetrahydropyridine analog (HPTP) of haloperidol
      influences dopamine ligand binding in baboon brain. An [123I]iodobenzamide (IBZM)
      SPECT study.
AB  - Haloperidol (HP) and its tetrahydropyridine dehydration product 4-(4
      chlorophenyl)-[4-(fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyrid ine (HPTP)
      are both metabolized in vivo to several pyridinium metabolites with potential
      neurotoxic properties similar to the neurotoxin 1-methyl-4-phenylpyridinium
      (MPP+), a metabolite of the parkinsonian-inducing agent 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). The effect of long-term HPTP treatment on the central
      nervous system of baboons (Papio ursinus) was studied using [123I]iodobenzamide
      (IBZM) and single photon emission computed tomography (SPECT) at 1-14 weeks after
      termination of HPTP treatment. Striatal dopamine receptor binding was measured
      semiquantitatively by calculating the IBZM count rate ratios of the basal ganglia
      to frontal cortex and basal ganglia to cerebellum. Relative striatal perfusion
      was assessed by similar 99mTc-HMPAO (hexamethylpropylene amine oxime) ratios.
      Time activity curves of IBZM from the brain structures suggest that HPTP
      treatment results in a marked reduction in central dopamine ligand binding, and
      in particular D2-like receptor binding. Increased washout of the ligand from all
      the brain structures investigated was seen in the HPTP-treated animals, also
      consistent with reduced binding. Cerebral blood flow in the control and HPTP
      treated groups was similar, indicating that this did not account for the reduced
      dopamine receptor binding of the IBZM ligand. These data suggest that treatment
      with HPTP induces significant effects on dopamine receptor binding that may
      contribute to some of the neurological disorders observed in humans undergoing
      chronic HP treatment.

PMID- 9037543
TI  - Differential regulation of genes encoding synaptic proteins by members of the Brn
      3 subfamily of POU transcription factors.
AB  - The three members of the Brn-3 subfamily of POU transcription factors have
      distinct effects on target gene expression. We show that the promoter of the gene
      encoding the presynaptic nerve terminal protein SNAP-25 resembles previously
      characterised target genes in being activated by Brn-3a and Brn-3c, but being
      repressed by Brn-3b. Unlike other target genes, however, the SNAP-25 promoter can
      be activated by either the N- or C-terminal activation domains of Brn-3a. In
      contrast to the SNAP-25 gene, the gene encoding the synaptic vesicle protein
      synapsin 1 is activated by all the Brn-3 factors, the first gene for which this
      activation pattern has been reported Interestingly, however, similar activation
      by all three Brn-3 factors can be observed if the SNAP-25 promoter is truncated
      by removal of sequences from -2200 to -288 relative to the transcriptional start
      site. Moreover, a region of the SNAP-25 promoter from -283 to -126 can render a
      heterologous promoter responsive to activation by all three Brn-3 factors.
      Differences in promoter structure may thus result in differences in the response
      to different Brn-3 factors, thus allowing these factors to produce diverse
      activation patterns of neuronally expressed genes, such as those encoding
      different synaptic proteins.

PMID- 9037542
TI  - Serotonin transporter antibodies: production, characterization, and localization
      in the brain.
AB  - Serotonin (5-HT) transporter, the mechanism for 5-HT high affinity uptake, is the
      essential component for the termination of 5-HT transmission. In order to
      identify transporter sites on 5-HT neurons or on other 5-HT uptaking cells, three
      rabbit antisera against cocaine sensitive-serotonin transporter (5-HTT) were
      produced. Antisera 5-HTT55 (against amino acid sequence 55-68 in cytoplasmic N
      terminal) and 5-HTT315 (against amino acid sequence 315-325, a 3rd external loop
      peptide) were produced against synthetic multiple-antigenic peptides (MAP).
      Antiserum 5-HTTN was produced against a fusion protein of the first 71 amino
      acids of N-terminal peptide expressed in recombinant DNA transformed bacteria.
      SDS-PAGE/Western blots indicate that 5-HTT55 and 5-HTT315 recognized bands of 74
      and 64 kDa in rat brains with densities in the order of cortex > or = hippocampus
      > cerebellum, but not in liver, or muscle. The 5-HTTN recognized the fusion
      protein expressed in the bacteria, and the 64 kDa band with a similar density
      profile in the rat brain regions, and negative in liver and muscle. The
      immunocytochemistry of all three antisera revealed 5-HTT-immunostaining (5-HTT
      im) in a pattern similar to 5-HT fiber distribution. 5-HTT55 and 5-HTT315
      stainings were punctate in appearance, while 5-HTTN outlined the fibers in the 5
      HT fiber areas, and neurons in raphe but not in substantia nigra or locus
      ceruleus. The preimmune serum and immune serum preabsorbed with 5-HTTN showed
      negative or diminished staining. Specific neurotoxin, 5,7-dihydroxytryptamine
      lesion removed all of the 5-HTTN fibers from the injection site, indicating, that
      5-HTTN-im fibers are 5-HT fibers in nature. Our study indicates that the three
      antibodies we produced recognize various domains of the 5-HTT. Our 5-HTT
      antibodies could be used as new markers of 5-HT fibers, and are particularly
      useful for the study of the plasticity of 5-HT fibers free of the complications
      involved with 5-HT content.

PMID- 9037544
TI  - Functional trkB neurotrophin receptors are intrinsic components of the adult
      brain postsynaptic density.
AB  - Neurotrophins have long been thought to act as target-derived factors that
      regulate the survival and differentiation of afferent neurons. Recently, brain
      derived neurotrophic factor (BDNF) was shown to elicit rapid increases in
      synaptic activity of cultured hippocampal neurons by enhancing responsiveness to
      excitatory input. These findings suggest a postsynaptic localization of
      neurotrophin receptors. In this study, we examined the expression of trkB, a high
      affinity receptor for BDNF, in the postsynaptic density (PSD), a proteinaceous
      specialization of the postsynaptic membrane. Western blot analyses with
      antibodies to trkB revealed localization to the PSD in adult rat cerebral cortex
      and hippocampus. Only the full-length, active form of trkB was detected in PSD
      samples. BDNF treatment of the adult cortical PSD resulted in a 5-fold increase
      in trkB autophosphorylation, supporting the contention that the PSD contains
      functional trkB. Truncated trkB, which does not contain the tyrosine kinase
      signaling domain, though present in membrane fractions, was undetectable in the
      PSD. The presence of trkB in the PSD is consistent with a role for neurotrophins
      in the regulation of synaptic activity via direct postsynaptic mechanisms.

PMID- 9037545
TI  - Effect of the weaver mutation on the expression of dopamine membrane transporter,
      tyrosine hydroxylase and vesicular monoamine transporter in dopaminergic neurons
      of the substantia nigra and the ventral tegmental area.
AB  - The adult homozygous weaver mutant mouse (wv/wv) is characterized by a loss of
      dopamine (DA) neurons in the nigrostriatal pathway. Quantitative in situ
      hybridization of three different dopaminergic markers: dopamine membrane
      transporter (DAT), tyrosine hydroxylase (TH), and vesicular monoamine transporter
      (VMAT2) was performed on individual dopaminergic cells of the substantia nigra
      pars compacta (SNC) and the ventral tegmental area (VTA) in 2-month-old wv/wv
      mice, in order to investigate the metabolic state of remaining dopaminergic cell
      bodies and gain further insight into modifications observed on dopaminergic nerve
      terminals in the striatum and the nucleus accumbens. Cellular expression of DAT
      mRNA in remaining dopaminergic cells of both the SNC and the VTA was decreased in
      the wv/wv mice compared to the wild-type mice (+/+). In contrast, the expression
      of TH and VMAT2 mRNA remained unchanged in the wv/wv mice. Furthermore, in 7-day
      old wv/wv mice, before the onset of cell death in the midbrain. DAT mRNA levels
      were reduced in dopaminergic neurons in both the SNC and VTA. In these animals,
      the cellular expression of TH mRNA remained unchanged. These results taken
      together indicate that DAT expression is one of the first targets in the ventral
      mesencephalon of the wv mutation, inducing a specific decrease of DA uptake in
      the striatum and the nucleus accumbens. The alteration of the DA membrane
      transporter could play a role in the progression of DA neuronal death in the wv
      mice.

PMID- 9037546
TI  - Structural characterization of osmoregulator peptides from the brain of the leech
      Theromyzon tessulatum: IPEPYVWD and IPEPYVWD-amide.
AB  - Neurons immunoreactive to an antiserum (a-OT) directed specifically against the C
      terminal part (prolyl-leucyl-glycinamide) of vertebrate oxytocin (OT) were
      detected in the brain of the leech Theromyzon tessulatum. With high pressure gel
      permeation chromatography followed by reversed-phase HPLC on brain extracts,
      evidence was given of the presence of three peptides (P1, P2, P3) immunoreactive
      to a-OT. Results of injection experiments in T. tessulatum and of titrations of
      each peptide at the different physiological stages of the animals which showed a
      peak in peptide P1 amount at stage 3B, indicated that P1 is the active OT-like
      peptide. Using three steps of reversed-phase HPLC, Edman degradation and
      electrospray mass spectrometry, two sequences for P1 (IPEPYVWD and IPEPYVWD
      amide) were found. These peptides differ from peptides to the
      oxytocin/vasopressin family and are unique in the animal kingdom. Confirmation of
      their action on the hydric balance and their distribution in the CNS were
      presented.

PMID- 9037547
TI  - Expression of L1 in primary astrocytes via a defective herpes simplex virus
      vector promotes neurite outgrowth and neural cell migration.
AB  - The neural cell adhesion molecule L1 is a transmembrane glycoprotein of
      approximately 200 kDa molecular weight that is a member of the immunoglobulin
      super family. Multiple functions of L1 have been reported, including cell-cell
      interactions, neurite elongation, axonal fasciculation, cell migration, and
      myelination. L1 plays important roles in neural development and axonal
      regeneration in the peripheral nervous system (PNS), however, in the adult it is
      only present on neurons in the central nervous system (CNS). In the present study
      we have used defective herpes simplex virus (HSV) vectors to express full-length
      human or rat L1 in cultured primary rat cortical astrocytes. Rat cerebellar
      granule cells, a rather homogeneous population of neurons, co-cultured on a
      substrate layer of L1-expressing astrocytes demonstrated increased migration and
      neurite extension compared with neurons co-cultured on lacZ-expressing astrocytes
      of uninfected astrocytes. There was no detectable difference between human and
      rat L1. Because this vector system can be used to confer phenotypic changes in
      primary nervous system cells it will be useful for in vitro and in vivo studies
      of neural regenerative sprouting and plasticity in the CNS.

PMID- 9037548
TI  - Hormonal and non-hormonal regulation of glutamine synthetase in the developing
      neural retina.
AB  - Two isoforms of the glucocorticoid receptor, with apparent molecular mass of 90
      and 95 kDa, are expressed in embryonic chicken neural retina. The 95-kDa receptor
      represents a hyperphosphorylated form of the 90-kDa receptor. Activation of the
      glucocorticoid receptor by cortisol results in a dose-dependent increase in
      receptor phosphorylation, translocation of receptor molecules into the nucleus
      and a decline in the total amount of the receptor. Activation of the
      glucocorticoid receptor can also be observed in the developing retinal tissue in
      ovo. At late embryonic ages, when the systemic level of glucocorticoids
      increases, a substantial quantity of receptor molecules becomes translocated into
      the nucleus, the relative level of the 95-kDa isoform increases, and the total
      amount of receptor declines. Activation of the receptor molecules in ovo
      correlates directly with an increase in transcription of the glucocorticoid
      inducible gene, glutamine synthetase. The close correlation between the increase
      in systemic glucocorticoids, activation of glucocorticoid receptor molecules and
      induction of glutamine synthetase gene transcription suggests that
      glucocorticoids are directly involved in the developmental control of glutamine
      synthetase expression. Long-term organ culturing of embryonic retinal tissue in
      the absence of hormone results in an increase in glutamine synthetase expression.
      This increase, which is only 5 to 10% of that observed in ovo, is not mediated by
      activated receptor molecules and represents a mechanism for non-hormonal
      regulation of glutamine synthetase.

PMID- 9037549
TI  - Exclusion of the beta-subunit of type II calmodulin kinase for the wobbler spinal
      muscular atrophy gene.
AB  - The wobbler mouse (wr) is an attractive model for studying motor neuron disease
      but the genetic defect is unknown. The beta-subunit of calmodulin kinase II (beta
      CaMK II) is a good candidate for the wr mutation because of its chromosomal
      localization and tissue distribution. In this report, we found normal levels of
      CaM KII mRNA and enzyme activity making it highly unlikely that a mutation in the
      beta-CaM KII gene is the cause of the wr phenotype.

PMID- 9037550
TI  - An antisense transgenic strategy to inhibit the myelin oligodendrocyte
      glycoprotein synthesis.
AB  - To understand the function of the myelin oligodendrocyte glycoprotein (MOG), a
      myelin specific protein of the central nervous system, transgenic mice were
      produced. The transgene is a fusion gene containing 1.9 kb of murine myelin basic
      protein promoter, 430 bp of rat MOG cDNA in the reverse orientation and 4.5 kb of
      human proteolipid protein gene. In spite of high expression of antisense MOG mRNA
      in the oligodendrocytes, MOG synthesis was not inhibited in transgenic mice. This
      lack of inhibition of MOG underlines the difficulties encountered with antisense
      transgenic strategies.

PMID- 9037551
TI  - The tyrosine kinase inhibitor methyl 2,5-dihydroxycinnimate disrupts changes in
      the actin cytoskeleton required for neurite formation.
AB  - In the current studies, we investigated the relationship between tyrosine
      phosphorylation and neurite formation. In SH-SY5Y neuroblastoma cells, the
      tyrosine kinase inhibitor methyl 2, 5-dihydroxycinnimate blocked neurite
      formation on laminin. This corresponded with inhibition of paxillin and focal
      adhesion kinase tyrosine phosphorylation as well as a disruption of actin
      filament organization and actin polymerization. This suggests that tyrosine
      phosphorylation helps direct changes in the actin cytoskeleton required for
      neurite formation.

PMID- 9037552
TI  - Activation of nitric oxide synthase gene expression by hypoxia in central and
      peripheral neurons.
AB  - In the present study we examined the effects of hypobaric hypoxia on neuronal (n)
      and endothelial (e) nitric oxide synthase (NOS) gene expression in the central
      and peripheral nervous system. Adult rats were exposed either to normoxia (room
      air) on to hypobaric hypoxia (0.4 atm) for 4, 12 or 24 h and cerebellum and
      nodose ganglion representing the central and peripheral neurons, respectively,
      were removed. Messenger RNAs encoding n- and eNOS as well as beta-actin were
      analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) technique.
      Hypoxia increased nNOS mRNA expression with maximal changes occurring after 12 h
      wherein mRNA levels were increased by 10.4 +/- 1.3 and 2 +/- 0.4 fold in nodose
      ganglion and cerebellum, respectively. Hypoxia, on the other hand, had no
      significant effect on eNOS and beta-actin mRNA levels. Analysis of nNOS protein
      and enzyme activity showed near doubling of these variables in both tissues after
      24 h of hypoxia, indicating that nNOS protein levels are increased and that the
      protein is functionally active. These observations demonstrate that 12-24 h of
      hypobaric hypoxia selectively activates nNOS gene expression, which is reflected
      in an increase in nNOS protein in central and peripheral neurons. It is suggested
      that up-regulation of nNOS leads to increased generation of nitric oxide, which
      in turn may contribute to the readjustments of cardio-respiratory systems during
      the early stages of chronic hypoxia.

PMID- 9037553
TI  - Effects of chronic lithium and electroconvulsive stimuli on cholecystokinin mRNA
      expression in the rat brain.
AB  - This study compares the effect of lithium (Li+) and electroconvulsive stimuli
      (ECS), two treatments commonly used in the treatment of affective disorders, on
      CCK mRNA expression in the rat brain. Two groups of rats receiving either 4 week
      Li+ or vehicle food supplementation and two groups receiving 6 ECS or 6 sham ECS
      during 2 weeks were studied. A significant decrease in CCK mRNA levels was seen
      in the caudate putamen both after Li+ as compared to vehicle and ECS as compared
      to sham ECS, 27 and 25%, respectively. A small (10%), yet significant, decrease
      was also seen in the inner entorhinal cortex after Li+. The results indicate that
      both Li+ and ECS inhibit CCK synthesis in the caudate putamen and are consistent
      with other findings of presumed decreased dopaminergic action in this part of the
      brain following these treatments.

PMID- 9037554
TI  - Expression of neurotrophins and their receptors in the developing and adult rat
      adrenal gland.
AB  - We have studied the postnatal expression of neurotrophins, their cognate high
      affinity trk receptors and the low-affinity NGF receptor (p75LNGFR) in the rat
      adrenal gland using RT-PCR. Neurotrophin mRNAs were detectable during the whole
      postnatal period. Strongest signals were obtained for BDNF and NT4/5. Expression
      of trkA, trkB, trkC and p75LNGFR was found at all ages studied. Signals for trkA
      were highest in the adult adrenal medulla, whereas signals for p75LNGFR were
      highest in the adult adrenal cortex. Cur data suggest still largely enigmatic
      roles for neurotrophins in functions of the adrenal medulla and possibly also the
      cortex.

PMID- 9037555
TI  - Localization of 5-HT4 receptor mRNA in rat brain by in situ hybridization
      histochemistry.
AB  - Oligonucleotide probes that recognize two cloned splice variants (5-HT4S and 5
      HT4L) of 5-HT4 receptors were used to study by in situ hybridization the
      localization in rat brain of mRNA encoding these receptors. A probe common to
      both variants reveals high levels of transcripts in olfactory tubercle, some
      components of the basal ganglia (caudate putamen, ventral striatum), medial
      habenula and hippocampal formation. Similar patterns of distribution are obtained
      with probes that recognize each splice variant individually, suggesting that no
      dramatic differences exist in their respective regional distribution. Comparison
      of mRNA distribution with receptor distribution as visualized with [125I]SB
      207710 indicates that 5-HT4 receptors are localized both somatodendritically in
      e.g. caudate putamen and on axon terminals in e.g. substantia nigra and globus
      pallidus.

PMID- 9037556
TI  - Epidemiology of squamous cell conjunctival cancer.
AB  - The etiology of squamous cell carcinoma of the conjunctiva (SCCC) is not well
      known. A possible role of UVB radiation is suggested by an excess of SCCC in
      tropical countries and by the association between squamous cell skin cancer and
      exposure to UVB. Human papillomavirus type 16 also may be involved, given that it
      has been detected in benign and malignant conjunctival lesions and is the primary
      etiological agent involved in carcinoma of the anogenital tract. To examine the
      relationship between UVB exposure and SCCC, population-based age-adjusted
      incidence rates of SCCC and of conjunctival melanoma and squamous cell cancer of
      the eyelid were plotted against the UVB insolation of each registry site.
      Incidence data were examined further for patterns of second primary cancers among
      people with SCCC. SCCC was rare in the United States, with an incidence rate of
      0.03 per 100,000 persons, although the rate was approximately 5-fold higher among
      males and whites. Regression analysis suggested a link between UVB exposure and
      SCCC rates (beta = 2.25; r = 0.58) that was as strong as that for squamous cell
      carcinoma of the eyelid (beta = 2.73; r = 0.62) and much stronger than for
      conjunctival melanoma (beta = 0.28; r = 0.02). Risk of a second malignancy after
      SCCC was not increased overall (20 observed and 14.1 expected), although a
      significant excess of salivary gland cancer (4 observed and 0.03 expected) and a
      borderline excess of lung cancer (6 observed and 2.4 expected) were noted. These
      observations suggest that UV radiation likely contributes to SCCC development.
      Additional research is needed to define the other exposures and host
      susceptibility that likely interact with UV-related genetic damage in the
      multifactorial development of this rare neoplasm.

PMID- 9037557
TI  - Nutritional and lifestyle habits and water-fiber interaction in colorectal
      adenoma etiology.
AB  - Adenomatous polyps are neoplasms that may progress to colorectal cancer. The role
      of diet and other lifestyle habits in their etiology is now being elucidated. The
      aim of this study was to evaluate effects of nutritional habits, weight and
      weight gain, tobacco smoking, and physical activity in adenoma etiology. A
      quantified dietary history questionnaire was designed to evaluate long-term
      dietary habits in addition to more recent ones. The study population comprised
      196 adenoma patients and matched asymptomatic, screened controls. Statistical
      analysis used multivariate conditional logistic models, adjusting for total
      energy intake and physical activity. Odds ratios (ORs) and 95% confidence
      intervals (CIs) for adenoma associated with highest versus lowest tertiles of
      mean daily intake were as follows: for energy, OR 3.7 and CI 2.1-6.7; for animal
      fat, OR 2.4 and CI 1.2-4.7; for tobacco smoking, OR 3.1 and CI 1.1-2.8; and for
      weight gain, OR 2.2 and CI 1.2-4.1 (P for linear trend for all, < or = 0.01).
      Significant negative associations were found with intake of total carbohydrates
      (OR, 0.3; CI, 0.1-0.7) and fluids (OR, 0.4; CI, 0.2-0.8) (P for both < 0.01) as
      well as for physical activity (OR, 0.6; CI, 0.3-0.9; P = 0.03). Increased risk
      for adenoma was observed with decreased intake of carotene (OR, 0.6; CI, 0.3-1.0;
      P = 0.06), vitamin E (OR, 0.6; CI, 0.3-1.0; P = 0.07), and dietary fiber (OR,
      0.6; CI, 0.3-1.3; not significant). The OR of interaction between water and
      dietary fiber was significant (OR, 0.7; CI, 0.6-0.9; P = 0.01), suggesting a
      synergistic protective effect. Specific dietary and lifestyle habits were
      identified as independent factors associated with colorectal adenomas; of special
      interest is the interaction between water and fiber intake. Avoiding these
      factors might delay or prevent neoplasia.

PMID- 9037558
TI  - Lung cancer in Mexican-Americans and African-Americans is associated with the
      wild-type genotype of the NAD(P)H: quinone oxidoreductase polymorphism.
AB  - Age-adjusted incidence rates for lung cancer are significantly lower for
      Hispanics compared with non-Hispanic whites or African-Americans; differences in
      genetic susceptibility have been postulated as one explanation for these ethnic
      differences. Recently, a polymorphism of the gene encoding NAD(P)H quinone
      oxidoreductase (NQO1) has been described. NQO1 is a cytosolic enzyme catalyzing
      the two-electron reduction of quinone substrates, which is thought to be involved
      in both metabolic activation and detoxification of carcinogenic agents that could
      be involved in lung carcinogenesis. The polymorphic variant of the gene (a C-to-T
      transition at base pair 609) is associated with reduced NQO1 activity and
      resistance to anticancer agents requiring reductive activation. We studied 177
      untreated lung cancer cases and 297 community controls, examining the prevalence
      of the NQO1 wild-type and variant alleles to assess whether the polymorphism was
      associated with lung cancer. Cases and controls were individuals of Mexican
      American (n = 222) or African. American (n = 252) ethnicity recruited from the
      Houston and San Antonio areas. Overall cases were more likely to carry two copies
      of the wild-type NQO1 allele compared with controls (odds ratio, 1.79; P =
      0.002). When cases and controls were stratified by ethnicity, the wild-type
      genotype was found to be approximately 2-fold more common among African-Americans
      (P < 0.001) than among Mexican-Americans. Multivariate analyses indicated a
      significant association of the wild-type genotype with lung cancer risk after
      controlling for the effects of age, gender, ethnicity, and smoking status (odds
      ratio, 1.80; 95% CI:1.09-2.97; P = 0.02). These results indicate a significant
      ethnic variation in the occurrence of the NQO1 base pair 609 transition and
      demonstrate an association of the wild-type genotype with lung cancer risk. Given
      the known role of NQO1 in the activation of potential lung carcinogens, the NQO1
      polymorphism should be investigated further as a possible genetic risk factor for
      lung cancer among minority populations.

PMID- 9037559
TI  - Strength of linkage disequilibrium between two vitamin D receptor markers in five
      ethnic groups: implications for association studies.
AB  - Markers in the 3' end of the vitamin D receptor gene have recently been
      associated with prostate cancer risk. To evaluate the adequacy of the commonly
      used BsmI restriction fragment length polymorphism as a marker of this locus, we
      genotyped 627 individuals from five ethnic groups for this marker, as well as for
      a polymorphic site in the 3' untranslated region of this gene. At the latter
      site, we identified 12 alleles, A13 to A24, of a poly(A) microsatellite. Allele
      size followed a bimodal distribution with distinct short (A13-A17) and long (A18
      A24) allele populations. Poly(A) allele frequency differed by ethnicity, with the
      frequency of short alleles being highest in non-Hispanic whites (41%),
      intermediate in Hispanics and African-Americans (31 and 29%, respectively), and
      lowest in Japanese-Americans and Chinese (8 and 9%, respectively). In each of the
      ethnic groups, some degree of coupling was observed between BsmI B and short
      poly(A) alleles and between BsmI b and long poly(A) alleles. However, the
      strength of the linkage disequilibrium varied by ethnicity, with departures from
      complete disequilibrium producing disagreement between the BsmI and poly(A)
      genotypes. Genotypic disagreement was lowest in Japanese-Americans and non
      Hispanic whites (6 and 7%, respectively), intermediate in Chinese and Hispanics
      (11 and 19%, respectively), and highest among African-Americans (37%), indicating
      that BsmI is not a good marker for the vitamin D receptor 3' untranslated region
      genotype in all populations. This finding may explain contradictory results from
      recent association studies using the BsmI marker.

PMID- 9037560
TI  - A note on the estimation of relative risks of rare genetic susceptibility
      markers.
AB  - The comparison of an incident case series with an incident series of second
      primary cancers, using either a case-control or follow-up study design, is
      proposed as an efficient method for evaluating the relative risk of a rare
      genetic susceptibility marker and its prevalence in the population, and for
      evaluating gene-environment interactions. The relative efficiency of this design
      versus a conventional case-control study is highly dependent on the population
      prevalence of the marker and its relative risk. However, for relatively rare but
      highly penetrant genes, the relative efficiency can be very high. In an example
      presented regarding a planned study of the p16 gene and its role in melanoma, a
      conventional case-control study may require up to 70 times as many subjects to
      achieve equivalent precision to the study of second primaries. The use of second
      primary cancers in this way requires assumptions about the validity of the
      classification of a new tumor as a second primary, the extent to which risk of a
      second cancer is influenced by treatment of the first cancer, and the nature and
      extent of surveillance bias. However, the problems of ascertaining a valid series
      of population controls are avoided. The study of second cancers represents an
      important and underused tool in molecular and genetic epidemiology.

PMID- 9037561
TI  - p53 haplotype determination in breast cancer.
AB  - Inheritance of certain germ line haplotypes consisting of three biallelic
      polymorphisms of p53 has been proposed as a risk factor for breast cancer and
      colorectal cancer [A. Sjalander et al., Carcinogenesis (Lond.), 17: 1313-1316,
      1996, and Carcinogenesis (Lond.), 16: 1461-1464, 1995]. In their studies,
      pairwise haplotypes of these three polymorphisms were estimated. Extended
      haplotypes were further projected from the pairwise combinations. To overcome the
      necessity to estimate pairwise and extended haplotype frequencies, a PCR method
      has been developed to determine the absolute extended p53 haplotypes in diploid
      genomes. The method requires allele-specific PCR, confirmed by restriction
      analysis, and successive amplicon analysis. It has been applied to a nested case
      control study of breast cancer (284 subjects; 99 cases and 185 controls; 182
      Caucasians, 56 Hispanics, and 46 African-Americans). Evidence is presented that
      minor variants of the intron 3, codon 72, and intron 6 polymorphisms were
      moderately elevated in Caucasian breast cancer cases (intron 3, P = 0.03 for
      genotype and P = 0.01 for allelic frequency; codon 72, P = 0.07 for genotype and
      P = 0.054 for allelic frequency; and intron 6, P = 0.02 for genotype and P = 0.02
      for allele frequency). Accordingly, analysis of haplotype distributions suggested
      an association of minor p53 haplotypes with breast cancer risk in Caucasians (P =
      0.07). The relative allelic frequencies in breast cancer cases compared with
      controls also differed by age and menopausal status; the 1-2-1 haplotype was
      overrepresented in postmenopausal cases (P = 0.02) and cases older than 50 years
      (P = 0.02), whereas the other minor haplotypes (1-1-2 and rare variants) were
      overrepresented in premenopausal cases (P = 0.003) and cases 50 years of age and
      younger (P = 0.02). Genotype distributions at each locus and for all control
      groups were consistent with Hardy-Weinberg equilibria. Differences in haplotype
      distribution were associated with ethnicity (Caucasians versus African-Americans
      and Caucasians versus Hispanics, P < 0.001). The new haplotyping method may be
      useful in the study of gene-environment interactions.

PMID- 9037562
TI  - Analysis of human urine for pyridine-N-oxide metabolites of 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanone, a tobacco-specific lung carcinogen.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary
      carcinogen in rodents and is believed to be a causative factor for lung cancer in
      smokers. NNK also may be involved in oral cancer etiology in users of smokeless
      tobacco products. Pyridine-N-oxidation of NNK and its major metabolite, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), produces NNK-N-oxide and NNAL
      N-oxide, respectively, which are detoxification products of NNK metabolism and
      are excreted in the urine of rodents and primates. Our goal is to develop a panel
      of urinary biomarkers to assess the metabolic activation and detoxification of
      NNK in humans. In this study, we developed methodology to analyze human urine for
      NNK-N-oxide and NNAL-N-oxide. The key step in the method was conversion of the N
      oxides to NNK and NNAL by treatment with Proteus mirabilis. The resulting samples
      were then analyzed essentially by methods that we have described previously. 4
      (Methylnitrosamino)-4-(3-pyridyl-N-oxide)-1-butanol (iso-NNAL-N-oxide) was used
      as internal standard. Levels of NNAL-N-oxide in smokers' urine ranged from 0.06
      to 1.4 pmol/mg creatinine, mean +/- SD 0.53 +/- 0.36 pmol/mg creatinine. Its
      presence was confirmed by high performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry. NNK-N-oxide was not detected in smokers'
      urine. Levels of NNAL-N-oxide in the urine of smokeless tobacco users ranged from
      0.02 to 1.2 pmol/mg creatinine, mean +/- SD 0.41 +/- 0.35 pmol/mg creatinine. The
      amounts of NNAL-N-oxide in urine were less than 20% of those of [4
      (methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL
      Gluc) and were approximately 50% as great as those of free NNAL. These results
      demonstrate that pyridine-N-oxidation is a relatively minor detoxification
      pathway of NNK and NNAL in humans. The method was applied to analysis of urine
      from 11 smokers who consumed a diet containing watercress. In an earlier study
      (S.S. Hecht et al., Cancer Epidemiol., Biomarkers & Prev., 4: 877-884, 1995), we
      showed that consumption of watercress, a source of phenethyl isothiocyanate
      (PEITC), caused an increase in urinary excretion of NNAL plus NNAL-Gluc. This was
      attributed to inhibition of alpha-hydroxylation of NNK by PEITC, as seen in
      rodents in which PEITC also inhibits the pulmonary carcinogenicity of NNK.
      However, PEITC also could have inhibited pyridine-N-oxidation of NNK and NNAL.
      The urine of these smokers was analyzed for NNAL-N-oxide. The results
      demonstrated that watercress consumption had no effect on levels of NNAL-N-oxide
      in urine, supporting the conclusion that PEITC does inhibit the metabolic
      activation of NNK in humans.

PMID- 9037563
TI  - Studies of esophageal balloon cytology in Linxian, China.
AB  - Esophageal cancer is the second leading cause of cancer death in China.
      Esophageal cancer has a very poor prognosis, principally because most tumors are
      asymptomatic until they are unresectable. Esophageal balloon cytology is an early
      detection method developed by Chinese scientists to identify resectable early
      cancers and precursor lesions. Previous studies have reported high sensitivities
      for detecting esophageal cancer in symptomatic patients. The current report
      describes several studies evaluating this diagnostic technique in asymptomatic
      individuals. A comparison of Chinese and U. S. cytological diagnoses of the same
      esophageal samples showed that the Chinese categories of precancerous neoplasia
      were more inclusive than the corresponding U. S. categories. Comparisons of both
      Chinese and U. S. cytological diagnoses with concurrent histological findings
      showed low (14-36%) sensitivities for the cytological detection of biopsy-proven
      cancers. Prospective follow-up studies of several screened cohorts showed a
      consistent progression of risk for developing esophageal cancer with increasing
      severity of initial cytological diagnosis. These preliminary studies suggest that
      esophageal balloon cytology is a useful technique that can benefit from
      additional research to improve its optimal performance.

PMID- 9037564
TI  - Is Ki-67 a better proliferative marker in the colon than proliferating cell
      nuclear antigen?
AB  - Endogenous markers of proliferating cells have increasingly supplanted the use of
      incubation of biopsy tissues in vitro with tritiated thymidine or with
      bromodeoxyuridine, thus avoiding the potential variation resulting from the
      incubation procedure. Antibodies to proliferating cell nuclear antigen (PCNA)
      such as PC10 have been promoted as optimal for this purpose, although
      considerable variation in colonic proliferating cells with this antibody has been
      reported. We have compared the detection of colonic proliferating cells in normal
      mucosa and adenomata using the PC10 monoclonal antibody (mAb) to PCNA and the Mib
      1 mAb to Ki-67 in formalin-fixed tissues using antigen retrieval solutions with
      microwaving. The PC10 antibody showed variable immunostaining of proliferating
      and nonproliferating cells with minor changes in primary antibody concentration
      or microwave conditions and between normal and adenomatous tissue. In contrast,
      Mib-1 immunostaining was quite constant with differing antigen retrieval and
      antibody conditions and similar staining of proliferating cells in colonic
      adenomas. Some loss of immunoreactivity occurred if the cut sections were not
      immunostained within approximately 1 week. These data suggest that whereas PCNA
      immunohistochemistry is satisfactory when carefully controlled in large
      chemopreventive studies, the Mib-1 mAb to Ki-67 is superior to PCNA antibodies in
      immunostaining proliferating cells in the formalin-fixed human colon.

PMID- 9037565
TI  - Gastric cancer risk factors in subjects with family history.
AB  - Until now, it has been unclear whether there are differences in various risk
      factor profiles for familial gastric cancer, i.e., gastric cancer among subjects
      with a family history of the disease. A total of 722 gastric cancer patients and
      2024 controls were admitted between 1985 and 1992 to a network of hospitals in
      the Greater Milan area. Of these, 88 cases and 103 controls who reported a family
      history of gastric cancer in first degree relatives were considered in the
      present analysis. There was no relationship between gastric cancer risk and
      tobacco smoking or alcohol drinking. Shorter duration of electrical refrigerator
      use was related to a nonsignificant increased risk and a high daily meal
      frequency was associated with an increased gastric cancer risk. Significant
      direct trends of risk were observed for pasta (odds ratio, OR = 4.20 for the
      highest versus the lowest tertile), bread (OR, 2.86), red meat (OR, 3.38), and
      preserved meat (OR, 1.90). Inverse associations were observed for increasing
      consumption of selected vegetables and fruits, chiefly peppers (OR = 0.31), total
      fruits (OR, 0.47), and citrus fruits (OR, 0.38). With reference to selected
      micronutrients, a significant inverse trend in risk with increasing consumption
      for beta-carotene (OR, 0.27) and ascorbic acid (OR, 0.20) was observed. These
      results suggest that dietary risk factors for subjects with a family history of
      gastric cancer in first-degree relatives are not appreciably different from well
      established risk factors of the disease in the general population.

PMID- 9037566
TI  - Work in agriculture, childhood residence, nitrate exposure, and testicular cancer
      risk: a case-control study in Denmark.
AB  - A population-based case-control study in Denmark investigated the hypothesis that
      parental occupation in agriculture increases the risk of testicular cancer in the
      offspring. Other factors investigated were: childhood residence on a farm, in the
      country, or in an area with high nitrate concentration in ground water, and the
      subjects' own occupation in agriculture. The only association that emerged was
      with childhood residence in the high-nitrate area. The excess risk was, however,
      confined entirely to men who did not grow up on a farm or in the country. This
      makes it very unlikely that nitrate exposure per se should be responsible.
      Further analyses revealed that the excess risk was confined largely to men who
      grew up in nonrural areas within Arhus County, where Denmark's second largest
      city is located, and an excess risk was also seen among men who grew up in
      Copenhagen Municipality, which is the center of the most urban area in Denmark.
      The geographic pattern of incidence is stronger for the area of childhood
      residence than for the area of residence at the time of diagnosis. This supports
      indirectly the idea that testicular cancer is caused by unidentified factors
      early in life.

PMID- 9037567
TI  - Correspondence re: C. Chen, K. E. Malone, J. Prunty, and J. R. Daling,
      Measurement of urinary estrogen metabolites using a monoclonal enzyme-linked
      immunoassay kit: assay performance and feasibility for epidemiological studies.

PMID- 9037568
TI  - Fosphenytoin (Cerebyx).
AB  - Fosphenytoin is a phosphate ester prodrug of phenytoin developed as a replacement
      for standard injectable sodium phenytoin. After absorption, phenytoin is cleaved
      (conversion half-life 8-15 min) from fosphenytoin. Unlike phenytoin, fosphenytoin
      is freely soluble in aqueous solutions (including standard intravenous solutions)
      and rapidly absorbed by the intramuscular route. Fosphenytoin has been tested
      successfully for three indications in humans: intramuscular maintenance dosing,
      intramuscular loading dose administration, and intravenous treatment of status
      epilepticus. Local toxicity (pain, burning, itching) is less by the intramuscular
      or intravenous route for fosphenytoin than for standard injectable sodium
      phenytoin. Systemic toxicity is similar with both preparations except that
      hypotension is less common and paresthesias are more common with fosphenytoin.

PMID- 9037569
TI  - Effects of pregnancy on various pathways of human antiepileptic drug metabolism.
AB  - Ratios of phenytoin and carbamazepine doses to steady-state plasma concentrations
      of the drugs (apparent clearances) increase in pregnant women. Mean phenytoin
      clearance to urinary unconjugated p-hydroxyphenytoin increased from 0.28 +/- SD
      0.18 to 0.74 +/- SD 0.37 L/day in 13 pregnant women; mean clearance to p
      hydroxyphenytoin glucuronide increased proportionately less (15.25 +/- SD 5.43 to
      31.94 +/- SD 16.30 L/day), the proportion of the metabolite that was conjugated
      falling from 98.4 +/- SD 0.72% to 97.65 +/- SD 0.67%. Mean clearances to urinary
      phenytoin and phenytoin-dihydrodiol did not increase. In 10 epileptic women, mean
      clearances of carbamazepine to urinary (a) carbamazepine-10,11-epoxide (1.66 +/-
      SD 1.2 to 3.70 +/- SD 2.09 L/day), (b) unconjugated carbamazepine-10,11-trans
      diol (33.93 +/- SD 10.21 to 47.01 +/- SD 19.58 L/day). (c) unconjugated
      carbamazepine-acridan (0.24 +/- SD 0.12 to 0.47 +/- SD 0.34 L/day), and (d)
      unconjugated 2-hydroxy-carbamazepine (0.08 +/- SD 0.09 to 0.66 +/- SD 1.14 L/day)
      all increased during pregnancy. Mean clearance to unconjugated 3-hydroxy
      carbamazepine decreased (0.53 +/- SD 0.25 to 0.18 +/- SD 0.23 L/day). In
      contrast, mean clearances of carbamazepine to the glucuronides of its first stage
      metabolites (carbamazepine-diol, 2- and 3-hydroxy-carbamazepine and carbamazepine
      acridan, respectively) did not increase in pregnancy. The conversion of
      carbamazepine to carbamazepine-epoxide increased proportionately more than the
      conversion of carbamazepine-epoxide to carbamazepine-diol. Pregnancy was thus
      associated with increased microsomal oxidations of phenytoin and carbamazepine,
      without proportionate increases in the subsequent hydrolysis of carbamazepine
      10,11-epoxide and in the O-glucuronidations of the earlier stage metabolites.

PMID- 9037570
TI  - The management of coexisting depression in patients with dementia: potential of
      calcium channel antagonists.
AB  - Depression frequently coexists with dementia, although in many cases the
      depression is not recognized clinically. Depression represents a major additional
      burden in dementia, not only for the patients but also for families, caregivers,
      and, economically, society as a whole. However, depression in patients with
      dementia does respond to treatment, and appropriate therapy can significantly
      improve the well-being of these patients. Depression in patients with dementia is
      currently treated with a variety of standard antidepressive agents (tricyclic
      antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase
      inhibitors), but none is free from significant side effects. Moreover, the use of
      these drugs is often complicated by a number of age-related factors or effects on
      the cholinergic neurotransmitter system. Consequently, an antidementia treatment
      with concomitant antidepressive properties and an acceptable benefit/risk ratio
      would represent an attractive therapeutic option. The pathogenesis of depression
      in patients with dementia is not well understood, but may be related to increased
      intracellular calcium ions in the CNS, the so-called "calcium hypothesis." This
      hypothesis may explain why some calcium antagonists exert psychotropic effects,
      including putative antidepressant activity. Animal models and clinical data
      provide support for the use of calcium channel antagonists for the treatment of
      depression, with the potential for good tolerability. The latter aspect is
      especially important for elderly patients with dementia. Although antidepressive
      effects have been seen with a number of calcium channel antagonists, the
      dihydropyridine derivative nimodipine shows particular potential for clinical
      use, perhaps because nimodipine is one of the most lipophilic of these drugs and
      therefore achieves high concentrations in the CNS, and because of the unique
      biochemical properties of the dihydropyridine compounds compared with other L
      type calcium channel blockers. Nimodipine also increases somatostatin levels in
      CSF, one of the cardinal biochemical deficits in Alzheimer's disease. Data
      obtained incidentally from the use of nimodipine in the treatment of elderly
      demented patients clearly demonstrate significant antidepressant activity by the
      drug in this patient group. Formal clinical evaluation is therefore recommended
      to establish more clearly the therapeutic benefits offered by nimodipine in
      patients who suffer from both dementia and depression.

PMID- 9037571
TI  - Dopamine hypersensitivity in migraine: role of the apomorphine test.
AB  - We investigated the effects of apomorphine administration at two different doses
      (2-10 micrograms/kg, s.c.) in 35 migraineurs in headache-free period and in 20
      age-matched healthy control subjects, with and without pretreatment with
      domperidone. Neither patients or controls complained of headache at either dose,
      whereas at the dose of 10 micrograms/kg migraineurs showed a statistically
      significant higher incidence of dopaminergic symptoms (nausea, vomiting,
      drowsiness, yawning, dizziness, sweating) than controls. Furthermore, symptoms
      due to postsynaptic dopamine receptors activation (i.e., nausea and vomiting)
      only appeared in migraineurs. No symptom, however, resembled those characterizing
      a spontaneous migraine attack. In conclusion, migraineurs show a lower threshold
      for dopamine receptor activation than normal subjects.

PMID- 9037572
TI  - Quantitative electromyography-guided botulinum toxin treatment of cervical
      dystonia.
AB  - The purpose of this study was to investigate the clinical and electromyographic
      effect of turn/amplitude analysis (TAA)-guided botulinum toxin administration in
      patients with cervical dystonia. Involuntary electromyographic activity was
      recorded from both sternocleidomastoidei, both splenii capites, and both trapezii
      muscles of 13 torticollis patients, aged 34-73 years, before and after botulinum
      toxin A (Dysport) application. Dystonic muscles were selected for the injection
      if mean turns/s exceeded a level of 200. Four weeks after treatment with a mean
      dose of 223 mu/subject, clinical improvement was observed in 12 patients (92%)
      and only one patient reported no effect. Electromyographic improvement could be
      observed in 10 patients (77%). Both turns/s and the amplitude/turn decreased by
      27% on the average after treatment. The electromyographic toxin effect showed a
      good correlation with the clinical toxin effect (r = 0.6). No dose dependency of
      the changes in turn/amplitude parameters could be observed. We found TAA a
      valuable modality for targeting and selecting dystonic muscles and for assessing
      the therapeutic benefit of the toxin.

PMID- 9037573
TI  - Neurobehavioral syndrome induced by H2-receptor blocker withdrawal: possible role
      of prolactin.
AB  - Cimetidine and ranitine are histamine H2-receptor blockers widely used for the
      treatment of gastric hypersecretion and duodenal pathologies. They are known to
      induce hyperprolactinemia in humans. Forty-six patients treated with cimetidine
      or ranitidine who were exhibiting a neurobehavioral syndrome after withdrawal of
      the drugs were selected. This syndrome was associated with a drop in plasma
      prolactin levels. The symptoms of this syndrome were greatly improved by
      restoration of treatment with the same drugs and reappeared when the treatment
      was again suspended. This syndrome was inhibited in 36 patients by administration
      of domperidone (30 mg/day), a drug inducing hyperprolactinemia without crossing
      the blood-brain barrier, as compared with 10 control patients treated with
      placebo. These results suggest that the drop in prolactin levels occurring when
      cimetidine and ranitidine are suspended may contribute to the development of this
      syndrome. Also, the withdrawal of H2-receptor blockers could be included among
      the possible causes of some neurotic syndromes.

PMID- 9037574
TI  - Effect of L-Dopa and the catechol-O-methyltransferase inhibitor Ro 41-0960 on
      sulfur amino acid metabolites in rats.
AB  - L-Dopa is the most effective drug known for the treatment of Parkinson's disease.
      However, the large doses required to treat this neurodegenerative disorder can
      significantly affect tissue concentrations of sulfur amino acid metabolites due
      to peripheral and central O-methylation. These effects include decreases in
      tissue concentrations of the biochemical methyl donor S-adenosylmethionine (SAM),
      increases in tissue concentrations of the methylation inhibitor S
      adenosylhomocysteine (SAH), and increases in plasma concentrations of
      homocysteine, recently identified as an independent risk factor for vascular
      disease. In the present study, the ability of the catechol-O-methyltransferase
      inhibitor Ro 41-0960 to prevent L-Dopa-induced changes in SAM, SAH, and
      homocysteine concentrations was determined in rats. Rats were injected
      intraperitoneally with Ro 41-0960 or vehicle 30 min prior to an intraperitoneal
      injection of L-Dopa or vehicle. One hour after the second injection, the rats
      were killed and their brains, livers, spleens, kidneys, and plasma collected. SAM
      and SAH concentrations were then determined in discrete brain regions and
      peripheral tissues, and total homocysteine concentrations were determined in
      plasma. In the rats treated with only L-Dopa, decreased SAM concentrations and
      increased SAH concentrations were found in all brain regions and peripheral
      tissues measured, and increased homocysteine concentrations were found in plasma,
      consistent with previous reports. In rats pretreated with Ro 41-0960, however,
      these L-Dopa-induced effects on sulfur amino acid metabolite concentrations were
      attenuated or prevented entirely. It remains to be determined if this sparing
      effect of Ro 41-0960 on sulfur amino acid metabolites has clinical significance.

PMID- 9037576
TI  - Life-threatening dysphagia following prolonged neuroleptic therapy.
AB  - We report the cases of two patients with complaints of dysphagia following long
      term neuroleptic therapy. Esophageal contrast radiography revealed that one
      patient suffered disruption of the normal swallowing activity of the
      pharyngoesophagus due to tardive dyskinesia. Her dysphagia disappeared following
      changes in her neuroleptic medications and the administration of clonazepam. The
      other patient demonstrated severe rabbit syndrome involving the glossopharynx.
      This 3-Hz rhythmic movement disorder resolved following injection of an
      anticholinergic agent. Thereafter, the addition of oral trihexyphenidyl to her
      medication regimen improved her dysphagia. It should be emphasized that the
      differential diagnosis of neuroleptic-associated dysphagia subtypes is important
      because therapeutic strategies differ depending on the subtype of this life
      threatening illness.

PMID- 9037575
TI  - Early combination of bromocriptine and levodopa in Parkinson's disease: a
      prospective randomized study of two parallel groups over a total follow-up period
      of 44 months including an initial 8-month double-blind stage.
AB  - To determine if the combination of levodopa (LD) plus bromocriptine (Br) in the
      early stages of Parkinson's disease (PD) permits reduction of LD dosage and
      consequently results in fewer motor fluctuations and dyskinesias, a double-blind,
      multicenter prospective study in 50 PD patients who had responded favorably to LD
      while under treatment with that drug for < or = 6 months was undertaken. Patients
      were randomized into two parallel groups (LD alone and LD plus Br). During the
      first placebo-controlled stage of the study lasting 8 months, association of a
      fixed dose of Br (15 mg/day) in the LD regimen did not allow a significant
      reduction in the daily LD dose. Still, in patients on combined LD plus Br, there
      was a tendency toward smaller daily requirements of LD as compared with those on
      LD alone, and the difference in LD dose between the two groups was significantly
      different (515.4 +/- 240 vs. 725.6 +/- 230 mg/day; p < 0.01) after 44 months of
      continuous treatment in the 40 patients still enrolled in the open-label stage.
      At that point in time, the mean dose of Br had been increased by 9.2 mg in the
      combined treatment group, and the mean dose of LD was 40.7% lower than in the
      group receiving LD alone. On subsequent evaluations, the number of patients with
      dyskinesias or describing wearing-off fluctuations severe enough to require
      changes in treatment was lower than in the group under combined therapy, the
      differences being significant after 20 and 44 months, respectively (36.8 vs. 9.5
      and 47.3 vs. 14.2%). Our results support early combined LD-Br therapy in PD, but
      no conclusions can be drawn as to whether this dopamine agonist exerts a
      preventive effect on the late side effects of LD or has another mechanism of
      action.

PMID- 9037577
TI  - Acute risperidone overdose.
AB  - Risperidone (Risperdal) is a recently released novel antipsychotic medication. It
      is different from the conventional neuroleptics, such as haloperidol, as it has
      both serotinergic and dopaminergic activity. It has a more tolerable side-effect
      profile compared with other antipsychotic medications. We review the literature
      regarding the side effects of risperidone use, describe a case of overdose with
      risperidone, and discuss the clinical sequelae and management of such an
      overdose.

PMID- 9037578
TI  - Bruxism secondary to antipsychotic drug exposure: a positive response to
      propranolol.
AB  - We present two cases of acute nocturnal bruxism occurring as an early side effect
      of antipsychotic drug treatment. The development of bruxism was coupled with the
      appearance of neuroleptic-induced akathisia. Both complications were relieved
      after the beta-adrenergic blocker propranolol was added, suggesting the
      involvement of the adrenergic and serotonergic central nervous systems, besides
      the dopaminergic system, in the pathogenesis of bruxism. The positive response of
      iatrogenic bruxism to propranolol implies that propranolol also deserves a trial
      for the treatment of noniatrogenic nocturnal bruxism.

PMID- 9037579
TI  - An open-label study of botulinum toxin A for treatment of tardive dystonia.
AB  - Tardive dystonia is a form of tardive dyskinesia for which there is little
      satisfactory treatment. We reviewed our experience at four movement disorder
      centers in the treatment of tardive dystonia with botulinum toxin A (BTX-A).
      Thirty-four patients with relatively localized tardive dystonia unresponsive to
      oral medications were treated with injections of BTX-A into dystonia muscles.
      Cervical dystonia was the most frequent manifestation of tardive dystonia in this
      group of patients. There was marked or moderate improvement in 29 of 34 patients.
      Eighteen of 24 patients with cervical dystonia showed either marked or moderate
      improvement. In this retrospective review, BTX-A provided useful symptomatic
      treatment for localized dystonia in patients with tardive dystonia unresponsive
      to other treatment. A controlled, prospective trial of BTX-A in tardive dystonia
      is warranted.

PMID- 9037596
TI  - Mapping expressed sequence tag sites on yeast artificial chromosome clones of
      Arabidopsis thaliana DNA.
AB  - We describe a method for efficient parallel mapping of expressed sequence tag
      (EST) sites onto yeast artificial chromosome (YAC) clones. The strategy involves
      an initial YAC clone pooling scheme that minimizes the number of required PCR
      amplifications. This is followed by parallel analysis of PCR amplicons of EST
      sequences. Using this method, we have screened 600 EST sites in combinatorial
      pools of 3449 YAC clones that contain Arabidopsis thaliana DNA inserts. The
      presence of these genes on YACs was detected by amplifying EST sequences with PCR
      and analyzing the reaction products by agarose gel electrophoresis. Of the 600
      ESTs, 271 were found to map to individual YACs. Software tools are presented that
      allow for the automated analysis of this electrophoresis data. Suggestions for
      the scale-up of this method to map large genomes are discussed.

PMID- 9037597
TI  - Identification and localization of the gene for EXTL, a third member of the
      multiple exostoses gene family.
AB  - Hereditary multiple exostoses (EXT) is an autosomal dominant disorder
      characterized by multiple bony outgrowths from the juxtaepiphyseal region of long
      bones. In a small proportion of cases, these exostoses progress to malignant
      chondrosarcomas. Genetic linkage of this disorder has been described to three
      independent loci on chromosomes 8q24.1 (EXT1), 11p11-13 (EXT2), and 19p (EXT-3).
      The EXT1 and EXT2 genes were isolated recently and show extensive sequence
      homology to each other. These genes are deleted in exostoses-derived tumors,
      supporting the hypothesis that they encode tumor suppressors. We have identified
      a third gene that shows striking sequence similarity to both EXT1 and EXT2 at the
      nucleotide and amino acid sequence levels, and have derived its entire coding
      sequence. Although the mRNA transcribed from this gene is similar in size to that
      from EXT1 and EXT2, its pattern of expression is quite different. We have
      localized this gene by fluorescence in situ hybridization to metaphase
      chromosomes and by whole genome radiation hybrid mapping to chromosome 1p36.1
      between DIS458 and DIS511, region that frequently shows loss of heterozygosity in
      a variety of tumor types. This gene, EXTL (for EXT-like), is therefore a new
      member of the EXT gene family and is a potential candidate for several disease
      phenotypes.

PMID- 9037598
TI  - A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial
      syndrome minimal critical region.
AB  - DGS and VCFS, haploinsufficiencies characterized by multiple craniofacial and
      cardiac abnormalities, are associated with a microdeletion of chromosome 22q11.2.
      Here we document synteny between a 150-kb region on mouse chromosome 16 and the
      most commonly deleted portion of 22q11.2. Seven genes, all of which are
      transcribed in the early mouse embryo, have been identified. Of particular
      interest are two serine/threonine kinase genes and a novel goosecoid-like
      homeobox gene (Gscl). Comparative sequence analysis of a 38-kb segment reveals
      similarities in gene content, order, exon composition, and transcriptional
      direction. Therefore, if deletion of these genes results in DGS/VCFS in humans,
      then haploinsufficiencies involving this region of chromosome 16 should
      recapitulate the developmental field defects characteristic of this syndrome.

PMID- 9037599
TI  - 4.5-Mb YAC STS contig at 50-kb resolution, spanning Xq25 deletions in two
      patients with lymphoproliferative syndrome.
AB  - Sequence-tagged site (STS) content mapping in yeast artificial chromosomes (YACs)
      was used to cover the region deleted in two patients affected with X-linked
      lymphoproliferative disorder. The order of markers includes, centromere to
      telomere, DXS8009-DXS1206-DXS8078-DXS8044-DXS982- DXS6811-DXS8093-AFM240xblO-
      DXS75-DXS737-DXS100-DXS6-DXS1046-DXS803 8. The order of six major markers is
      confirmed by fluorescent in situ hybridization, and all the markers assigned by
      linkage mapping fall within a 1.6-cM interval. The contig comprises 90 clones
      containing 89 STSs, yielding a resolution of 50 kb; DNA in a gap just telomeric
      to DXS8044 has not been found in > 20 equivalents of YACs or bacterial clones.
      The two deletions were found to have centromeric breakpoints that lie close to
      DXS1206 and may be identical; the telomeric breakpoints are -150 kb apart, one
      falling between DXS737 and DXS100, the other between DXS100 and DXS1046. Several
      STSs near the breakpoints show weak amplification from more than one site; one
      gives products from three groups of YACs, and lie, respectively, within 50 kb of
      the centromeric and the two telomeric deletion borders. Such partially duplicated
      segments of DNA are candidates for involvement in the formation of the deletions.

PMID- 9037600
TI  - Telomeric organization of a variable and inducible toxin gene family in the
      ancient eukaryote Giardia duodenalis.
AB  - Giardia duodenalis is the best-characterized example of the most ancient
      eukaryotes, which are primitively amitochondrial and anaerobic. The surface of
      Giardia is coated with cysteine-rich proteins. One family of these proteins,
      CRP136, varies among isolates and upon environmental stress. A repeat region
      within the CRP136 family is interchangeable by a cassette-like mechanism,
      generating further diversity in repeat size, copy number, and sequence. Flanking
      the 5' region of the CRP136 family is a novel protein kinase gene and an ankyrin
      homolog, creating a conserved unit. A short spacer separates the ankyrin gene
      from the variable, tandem array of rDNA gene units at a common breakpoint within
      the large subunit gene, which is followed by the (TAGGG)n telomeric sequence.
      Transcriptional up-regulation of the CRP136 family is accompanied by a switch in
      mRNA length and promoter, of de novo expression, and suggests that CRP136 mRNA
      induction is under the control of a telomerically regulated position effect,
      which evolved very early in the eukaryotic lineage.

PMID- 9037601
TI  - Gene identification in 1.6-Mb region of the Down syndrome region on chromosome
      21.
AB  - The Down syndrome (DS) region has been defined by analyses of partial trisomy 21.
      The 2.5-Mb region between D21S17 and ERG is reportedly responsible for the main
      features of DS. Within this 2.5-Mb region, we focused previously on a distal 1.6
      Mb region from an analysis of Japanese DS patients with partial trisomy 21.
      Previously we also performed exon-trapping and direct cDNA library screening of a
      fetal brain cDNA library and identified a novel gene TPRD. Further screening of a
      fetal heart cDNA library was performed and a total of 44 possible exons and 97
      cDNA clones were obtained and mapped on a BamH1 map. By rescreening other cDNA
      libraries and a RACE reaction, we isolated nearly full-length cDNAs of three
      additional genes [holocarboxylase synthetase (HCS), G protein-coupled inward
      rectifier potassium channel 2 (GIRK2), and a human homolog of Drosophila
      minibrain gene (MNB)] and a coding sequence of a novel inward rectifier potassium
      channel-like gene (IRKK). The gene distribution and direction of transcription
      were determined by mapping both ends of the cDNA sequences. We found that these
      genes, except IRKK, are expressed ubiquitously and are relatively large,
      extending from 100 kb to 300 kb on the genome. These nearly full-length cDNA
      sequences should facilitate understanding of the detailed genome structure of the
      DS region and help to elucidate their role in the etiology of DS.

PMID- 9037602
TI  - A collection of 1814 human chromosome 7-specific STSs.
AB  - An established goal of the ongoing Human Genome Project is the development and
      mapping of sequence-tagged sites (STSs) every 100 kb, on average, across all
      human chromosomes. En route to constructing such a physical map of human
      chromosome 7, we have generated 1814 chromosome 7-specific STSs. The
      corresponding PCR assays were designed by the use of DNA sequence determined in
      our laboratory (79%) or generated elsewhere (21%) and were demonstrated to be
      suitable for screening yeast artificial chromosome (YAC) libraries. This
      collection provides the requisite landmarks for constructing a physical map of
      chromosome 7 at < 100-kb average spacing of STSs.

PMID- 9037603
TI  - Incognito rRNA and rDNA in databases and libraries.
AB  - Both ribosomal DNA (rDNA) and ribosomal RNA (rRNA) are over-represented in the
      starting material for genomic and cDNA libraries; thus, their sequences have the
      potential of repeatedly entering the various databases. When DNA (both
      transcribed and intergenic spacer regions) is used as query sequence, a great
      number of matches are found in the databases, particularly in the EST database,
      and to a lesser extent among genomic sequences and STSs, which are not identified
      as rDNA. We discuss the following explanations for the widespread occurrence of
      rDNA in cDNA and genomic DNA libraries: pseudogenes of rRNA in other genomic
      locations, mRNA-derived pseudogenes that reside in rDNA, cDNAs derived from rRNA
      [either by self-priming or by internal oligo(dT) priming], cDNAs derived from
      actual transcripts of the rDNA intergenic spacer, and genomic DNA contamination
      of RNA preparations. Because so many database entries contain unidentified rDNA,
      we recommend that all sequence submissions be checked (by the submitters) for the
      presence of structural RNAs in addition to repetitive sequences.

PMID- 9037604
TI  - Identification and analysis of expression of human VACM-1, a cullin gene family
      member located on chromosome 11q22-23.
AB  - We have localized the human homolog of the rabbit vasopressin-activated calcium
      mobilizing receptor VACM-1 to a region close to the gene for ataxia
      telangiectasia ATM on chromosome 11q22-23. We have determined the complete amino
      acid sequence of the human Hs-VACM-1 protein, which is 780 amino acids long. The
      human and rabbit sequences are highly conserved, differing at only seven amino
      acids. Northern analysis of the human gene showed expression in a wide range of
      human tissues. The Hs-VACM-1 gene has homology with the Caenorhabditis elegans
      gene Ce-cul-5, a member of a family of cullin genes that are involved in cell
      cycle regulation and that might, when mutated, contribute to tumor progression.

PMID- 9037605
TI  - A chromosome-specific microdissected library increases marker density on bovine
      chromosome 1.
AB  - Genetic resolution of bovine chromosome 1 (BTA1) linkage group was significantly
      increased by screening for microsatellite clones a microdissected library
      constructed from a bovine cell line carrying a t(1;29) translocation. Eighty-five
      percent of the microsatellites (ms) (46/54) identified were informative in the
      USDA/MARC mapping population, and 96% of these ms (44/46) linked to BTA1 (LOD >
      3.0). When merged with 40 existing BTA1 markers the genetic map spanned 153.8 cM
      (sex-averaged interval, 1.9 cM). The fourfold improvement in marker density of
      BTA1 provides a genetic map that enhances mapping of quantitative trait loci and
      implementation of marker assisted selection.

PMID- 9037606
TI  - High-throughput microsatellite analysis using fluorescent dUTPs for high
      resolution genetic mapping of the mouse genome.
AB  - The use of fluorescent end-labeled primers has proved successful for rapid,
      semiautomated genotyping of microsatellite loci. However, custom synthesis is
      expensive and costs can be prohibitive when a wide range of markers is to be
      analyzed for only a few genotypings. This particularly applies to high-resolution
      genetic mapping in the mouse either in the construction of global maps or in the
      production of local high-resolution genetic maps for positional cloning. We
      demonstrate here the use of fluorescent dUTPs for cost-effective, high-throughput
      microsatellite genotyping in the mouse. This alternative to the use of
      fluorescent end-labeled primers for semiautomated genotyping is potentially
      applicable to the construction of linkage maps in other species.

PMID- 9037607
TI  - DNA amplification.
AB  - The polymerase chain reaction has become a mainstream tool for the molecular
      biologist. The sensitivity, efficiency, and speed of this method is unparalleled
      for the amplification and detection of exquisitely minute quantities of nucleic
      acids. Through repetitive cycles of heat denaturation of samples, followed by the
      base pairing of primers designed to identify one DNA sequence among the cellular
      heterogeneity, and finally synthesis of new DNA strands identical to the target,
      single molecules and individual genes can be detected and subsequently
      characterized. This method has revolutionized the study of gene organization,
      structure, and expression, not to mention offering newer, faster, and more
      economical means for the clinical detection infectious disease. That PCR has been
      fruitful is undisputed; however, the method is not without shortcomings. Among
      the major limitations of this method are the absolute requirement for well
      designed primers, the super sensitivity of this method to biological contaminants
      from any of a variety of sources, and subtle, though very important, inter- and
      intra-laboratory variations in technique.

PMID- 9037608
TI  - Branched DNA for quantification of viral load.
AB  - This is a summary of a presentation made at the 13th International Convocation on
      Immunology. Nucleic acids in patient samples can be quantified directly using a
      solid phase nucleic acid hybridization assay based on branched DNA (bDNA) signal
      amplification technology. For example, HIV RNA is detected in a plasma sample by
      hybridization of multiple specific synthetic oligonucleotides to the target, 10
      of which capture the target onto the surface of a microwell plate and 39 of which
      mediate hybridization of branched DNA molecules to the pol region of each HIV RNA
      molecule. Alkaline phosphatase-labeled probes bind to each arm of the branched
      DNA molecules. Detection is achieved by incubating the complex with a
      chemiluminescent substrate and measuring the light emission. The signal is
      directly proportional to the level of target nucleic acid, and the quantity of
      HIV RNA in a sample is determined by comparison with a 4-point standard curve. In
      order to ensure that different subtypes of HIV-1 were detected and quantified
      equally, in vitro RNA transcripts of the pol region of HIV subtypes A-F were
      purified and quantified by OD 260, phosphate analysis, and hyperchromicity. These
      characterized transcripts were then quantified using the bDNA assay. Comparisons
      were made using a ratio of signal per attomole for each transcript. Genetic
      subtypes A-F quantified within a factor of 1.5, indicating that the bDNA assay
      can be used to measure viral load in clinical samples regardless of genotype.
      Accuracy is important because several studies indicate that there may be a
      threshold level of virus which predicts progression of HIV disease. Detection of
      change in viral load is important in determining the efficacy of therapy. The
      bDNA assay for HCV RNA can be used to determine level of virus in HCV-infected
      individuals and assist in establishing prognosis prior to initiation of alpha
      interferon therapy. Patients with lower levels of virus are more likely to have a
      sustained response to therapy. Patients who respond to treatment typically have a
      rapid decline in virus load within one to four weeks of the start of therapy.
      Many patients relapse when therapy is discontinued as evidenced by a rise in
      virus load to near pre-treatment levels. Sustained response is most often seen
      with patients who have lower pre-treatment levels of RNA.

PMID- 9037609
TI  - NASBA technology: isothermal RNA amplification in qualitative and quantitative
      diagnostics.
AB  - Nucleic acid amplification technologies allow for the development of highly
      sensitive and specific diagnostic assays. The capacity to amplify and detect
      analyte targets, which may be present in a clinical sample as a single copy; is
      characteristic of many of these amplification technologies. NASBA is an
      isothermal method of nucleic acid amplification with such capability, and is
      particularly well suited for the amplification of RNA analytes. NASBA utilizes
      the coordinated activities of three enzymes (AMV-RT, RNase H, T7 RNA polymerase),
      and two oligonucleotide primers which are specific for the analyte target. The
      amplification process is part of a total system which includes a versatile
      nucleic acid isolation procedure, and powerful detection methodology. In this
      report, the development of NASBA technology for the detection of human Retrovirus
      RNA will be discussed. Specifically, a qualitative NASBA assay for the RNA of
      HTLV I, and a quantitative NASBA assay for HIV-1 will be described.

PMID- 9037610
TI  - Concerted use of immunologic and ultrastructural analyses in diagnostic medicine:
      immunoelectron microscopy and correlative microscopy.
AB  - Electron microscopy (EM) is a valuable tool in diagnostic medicine, and in some
      cases, can be enhanced by immunological methods. A major medical application of
      EM, diagnostic virology, can frequently be augmented by employment of
      immunological reagents. Three immunoelectron microscopy (IEM) methods,
      aggregation, coating, and gold labeling, provide means for serotyping viruses;
      aggregation by antibody can also be used to concentrate viruses in dilute
      suspension or to serotype them. As a research tool, IEM can be useful in studying
      the relationship of various pathogen proteins to the infected cells or tissues.
      Delineating the subcellular location of viral components can yield information
      about how virions are constructed, and hence, suggest methods and compounds for
      inhibiting that process. Conversely, labeling virus-infected cells with
      antibodies against various cell receptors and proteins can yield information
      about the association of the proteins with budding virions. Another research
      example is the identification by immunological staining of virus-infected cells
      for subsequent ultrastructural identification of the specific cell type involved.
      Electron microscopy and immunolabeling methods are also useful in the diagnosis
      of immune complex disorders, including various forms of postinfectious immune
      complex glomerulonephritis. Precise analysis of immune complex deposits can be
      accomplished by using EM to pinpoint their location and immunohistology to probe
      their composition. Finally, a variety of optical microscopic techniques,
      including some involving immunofluorescent labeling, can be used to identify
      areas of interest in inhomogeneous tissues for further study by EM.

PMID- 9037611
TI  - Adsorption-induced antigenic changes and their significance in ELISA and
      immunological disorders.
AB  - The functional properties of 125I-labeled antibodies and antigens adsorbed on
      polystyrene and silicone were compared to their counterparts immobilized by non
      adsorptive methods. Less than 20% of polyclonal (pAb) and 1-2% of monoclonal
      (mAb) capture antibody equivalents remained functional after adsorption as a
      monolayer. Survivability circa doubled or was totally rescued, when the same
      antibodies were immobilized via a streptavidin bridge or by using a first stage
      polyclonal antiglobulin capture antibody, respectively. Similarly, the
      antigenicity of bovine IgGs for pAb and mAb anti-IgGs was highest when the IgGs
      were immobilized via a streptavidin bridge or when secondarily adsorbed to an
      albumin monolayer. IgGs in these configurations were significantly more antigenic
      than when directly adsorbed on polystyrene or a silicone elastomer. Similar
      activity was seen after adsorption on polystyrene or silicone. Interestingly,
      these IgGs were equally antigenic when denatured and subsequently adsorbed in 6M
      guanidine-HCl versus adsorption in PBS without prior denaturation. Although many
      of the above finding on antibodies and antigens could be explained by the greater
      accessibility of antigenic epitopes or antibody binding sites when molecules are
      immobilized by some type of underlying molecular layer, we also show that certain
      mAb and pAbs preferentially recognized allotopes on IgG2a when IgG2a was
      adsorbed. Furthermore, such antigenicity was highest when IgG2a was adsorbed at
      low, sub-monolayer concentrations. Finally, we show that differences in
      antigenicity need not be related to the method of immobilization, but can also
      result from differences in the microenvironment of the epitope. This was
      demonstrated using a filamentous phage clone specific for fluorescein (FLU). This
      clone recognizes the fluorescein hapten differently depending on the carrier
      protein used and the method of conjugation. Data presented in this report
      indicate that antibodies and antigens adsorbed on hydrophobic polymers undergo
      changes in their functional properties. Data suggest that both changes in
      conformation and the accessibility of antigen epitopes or antibody binding sites,
      most likely occur. Especially in the case of the latter, the functional
      concentration may be 1-2 orders of magnitude lower than the antibody protein
      concentration. These observations have implications for immunodiagnostics and
      emphasize the need to determine the specificity of an antibody in the assay in
      which it is employed and to make no assumptions about the behavior of solid-phase
      antigens and antibodies from their behavior in solution. Our studies are also
      relevant to the use of silicone medical prostheses. The antigenicity of IgGs
      adsorbed on silicone as a multilayer (secondary layer) is much higher than when
      directly adsorbed. Since such surfaces would be exposed to very high protein
      concentrations in vivo, multilayers not a monolayer, would be expected. Thus it
      would seem from these studies that host protein adsorbed on silicone would be
      expressed to the immune system at the surface of multilayers. This being the
      case, it seems unlikely that the adsorption of host protein in vivo would
      generate new epitopes against which the host's immune system could respond and
      subsequently initiate an autoimmune syndrome.

PMID- 9037612
TI  - Rapid diagnosis of periodontal infections: findings in AIDS patients.
AB  - A small number of bacterial pathogens in the human oral cavity cause the
      different forms of periodontal disease. Of the approximately two hundred
      different oral bacterial species, about a dozen have been associated with these
      diseases including localized juvenile periodontitis, rapidly progressing
      periodontitis, and adult periodontitis. These species include Actinobacillus
      actinomycetemcomitans, Bacteroides forsythus, Campylobacter rectus, Porphyromonas
      gingivalis, and Prevotella intermedia. Several rapid methods have been developed
      to detect these species in clinical samples. These include immunologic methods
      such as immunofluorescence, nucleic acid assays such as DNA-DNA hybridization in
      dot blots and enzyme assays. Immunofluorescence microscopy has been used to
      determine the prevalence and relative proportions of these pathogens in dental
      plaque samples from 194 subjects including HIV-infected and uninfected male
      homosexuals and intravenous drug users.

PMID- 9037613
TI  - Uses of biosensors in the study of viral antigens.
AB  - The introduction in 1990 of a new biosensor technology based on surface plasmon
      resonance has greatly simplified the measurement of binding interactions in
      biology. This new technology known as biomolecular interaction analysis makes it
      possible to visualize the binding process as a function of time by following the
      increase in refractive index that occurs when one of the interacting partners
      binds to its ligand immobilized on the surface of a sensor chip. None of the
      reactants needs to be labelled, which avoids the artefactual changes in binding
      properties that often result when the molecules are labelled. Biosensor
      instruments are well-suited for the rapid mapping of viral epitopes and for
      identifying which combinations of capturing and detector Mabs will give the best
      results in sandwich assays. Biosensor binding data are also useful for selecting
      peptides to be used in diagnostic solid-phase immunoassays. Very small changes in
      binding affinity can be measured with considerable precision which is a
      prerequisite for analyzing the functional effect and thermodynamic implications
      of limited structural changes in interacting molecules. On-rate (ka) and off-rate
      (kd) kinetic constants of the interaction between virus and antibody can be
      readily measured and the equilibrium affinity constant K can be calculated from
      the ratio ka/kd = K.

PMID- 9037614
TI  - Identification and function of host defense cells by flow cytometry.

PMID- 9037615
TI  - Application of flow cytometry in transplantation medicine.
AB  - Immunological rejection remains a major barrier to successful organ
      transplantation. Consequently, immunosuppressive intervention to prevent or
      control the rejection process renders the transplant recipient susceptible to
      infectious diseases. Flow cytometry has become a useful tool for monitoring
      immunological responses in transplant recipients. There are three areas of
      clinical transplantation immunology that may benefit from this technology. First,
      characterizing and classifying alloreactive antibodies by flow cytometry
      identifies high-risk donor and recipient combinations with greater precision.
      Second, the ability to detect subtle changes in the cellular components of the
      immune system cytometrically may facilitate the differential diagnosis of
      rejection, infection, and iatrogenic toxicity. Finally, the ease with which flow
      cytometry determines the adequacy or inadequacy of immunosuppressive therapy
      through T cell receptor analyses serves to maximize the beneficial effects of
      engraftment.

PMID- 9037616
TI  - Critical assessment of gene amplification approaches on the diagnosis of
      tuberculosis.
AB  - The resurgence of tuberculosis prompted the development of a number of new
      options for the rapid laboratory diagnosis of Mycobacterium tuberculosis (MTB).
      One of the most promising and exciting methodologies has been the introduction of
      assays employing amplification technology to detect MTB directly in clinical
      specimens. Although amplification assays hold significant promise to improve the
      laboratory diagnosis of tuberculosis, the decision to perform or not perform
      these assays is complicated. The performance of in-house polymerase chain
      reaction (PCR) assays and two commercially-prepared assays. GenProbe's AMTD test
      and Roche's AMPLICOR PCR assay are reviewed. Regardless of the amplification
      format, all assays have decreased sensitivity with specimens that are acidfast
      bacilli (AFB) stain-negative. Data from these studies and others indicate
      possible potential pitfalls of amplification assays, those being sampling errors,
      the presence of substances in clinical specimens that inhibit the amplification
      assay, and clinical utility. In light of these findings, the possible roles for
      these assays in the clinical microbiology laboratory are reviewed. In addition,
      factors such as cost, assay performance, etc. are discussed in order to
      facilitate the decision-making process concerning whether an amplification assay
      would be appropriate in a particular laboratory setting.

PMID- 9037617
TI  - Borrelia burgdorferi infection: clinical diagnostic techniques.
AB  - Borrelia burgdorferi is a tick-borne spirochete and the etiologic agent of Lyme
      disease. This pathogen now accounts for 91% of vector-borne infections in the
      United States, and from a public health viewpoint is one of our major emerging
      infectious disorders. Specific properties of B. burgdorferi have resulted in
      diagnostic problems, including the lack of a readily available laboratory assay
      to detect active infection. Most laboratory testing for Lyme disease relies on
      serologic documentation of prior exposure to the agent. However, such testing
      detects asymptomatic infections, and does not detect seronegative infections. In
      addition, antibody tests for Lyme disease are not standardized. Cases of Lyme
      disease are both underdiagnosed and overdiagnosed. This review will discuss the
      spirochetal properties which contribute to diagnostic difficulties, will discuss
      current laboratory diagnostic tests, including serology and detection of B.
      burgdorferi DNA, and will discuss diagnostic tests in development, including
      recombinant-based serologic assays and detection of B. burgdorferi antigens.

PMID- 9037618
TI  - The toxins of group A streptococcus, the flesh eating bacteria.
AB  - Streptococcus pyogenes causes a wide variety of infections in individuals of all
      ages in most countries of the world. Because of the frequency with which these
      infections occur, physicians are quite familiar with the diversity of clinical
      presentations associated with the Group A streptococcus. Yet in the late 1980's,
      a severe form of streptococcal infection, the Streptococcal Toxic Shock Syndrome,
      emerged and has persisted for the last 10 years. This syndrome is associated with
      invasive soft tissue infections and the early onset of shock and organ failure.
      The purpose of this paper is to briefly describe the epidemiologic and clinical
      features of the Streptococcal Toxic Shock Syndromes and to emphasize the role
      that toxins produced by S. pyogenes play in the pathogenesis of this disease.

PMID- 9037619
TI  - Diagnosis of chlamydial infection in the pediatric population.
AB  - The genus Chlamydia now contains 4 species, 2 of which, Chlamydia trachomatis and
      C. pneumoniae are important human pathogens. Both organisms cause infections in
      children and adults, but infection in children pose a unique set of problems. As
      C. trachomatis is primarily a sexually transmitted disease, the presence of
      rectal or genital infection in a prepubertal child has been used as evidence of
      sexual abuse. Although there are several categories of non-culture tests that
      have bear approved for genital sites in adults, these tests are not approved for
      these sites in children. Of these tests in rectal and vaginal specimens in
      children have been associated with a high rate of false positives. C. pneumoniae
      is emerging as a frequent cause of community acquired pneumonia in adults and
      children. Because culture is not generally available, serologic diagnosis is used
      more frequently. However, currently available serologic methods appear to be
      insensitive in children. The availability of a commercial PCR test will greatly
      facilitate the diagnosis of C. pneumoniae infections in children.

PMID- 9037620
TI  - DFA, EIA, PCR, LCR and other technologies: what tests should be used for
      diagnosis of chlamydia infections?
AB  - For many years, isolation in tissue culture (TC) was considered the test of
      choice for diagnosis of Chlamydia trachomatis infection. Non-culture tests, such
      as direct fluorescent antibody (DFA) and enzyme immunoassay (EIA) which detected
      chlamydial antigens in clinical specimens, made chlamydia diagnostic tests more
      widely available. DFA and EIA were less sensitive than TC and had some false
      positive results which compromised our ability to use these tests in low
      prevalence settings. Direct nucleic acid probes are available, but do not appear
      to be more sensitive than EIA. It was only with the introduction of amplified DNA
      tests [polymerase chain reaction (PCR) and ligase chain reaction (LCR)] that non
      culture tests became available that were actually more sensitive than TC.
      Unfortunately these tests are also more expensive than the antigen detection
      methods. Until there is a fairly sophisticated cost benefit analysis or a change
      in the pricing of these tests, it seems obvious that TC will remain, the best
      choice where medical/legal implications are important, DFA will probably remain a
      widely used tests for laboratories that process relatively small numbers of
      specimens and EIAs will play a role where cost is major factor and large numbers
      of specimens require bulk processing. Where they are affordable, the amplified
      DNA tests are to be preferred as they are far more sensitive than these other non
      culture tests.

PMID- 9037622
TI  - Immunodiagnosis of schistosomiasis.
AB  - The most efficacious and practical means of diagnosing human schistosomiasis is
      based on the detection of infection-specific antibodies. Because of their high
      sensitivity and specificity, antibody assays remain the most practical assays for
      epidemiologic studies and patient management. Antibody assays are particularly
      useful in the diagnosis of schistosomiasis in visitors from developed countries
      to endemic areas. These patients are often lightly infected, and tests that
      depend on detection of ova or circulating antigens are not reliable for these
      type of light and acute infections. Initial screening may be performed in the
      field or laboratory with the FAST-ELISA, using adult microsomal antigens. Species
      specific confirmation is obtained by immunoblots with the same antigens.

PMID- 9037621
TI  - Molecular diagnosis of Helicobacter pylori.
AB  - H. pylori infection can be diagnosed with many different tests. If the patient is
      undergoing endoscopy with gastric biopsies, culture and histology remain the
      diagnostic methods of choice. Indirect tests include rapid urease tests, urea
      breath tests, and serology. Molecular methods such as PCR offer marginal
      improvements when done on biopsy material, but has the advantage of being able to
      accurately identify H. pylori in areas outside the stomach where cultures usually
      fail. PCR can detect low numbers of organisms in gastric juice, bile, stool and
      oral secretions. Because of its high sensitivity it can also be used for
      epidemiologic investigations of environmental sources. However, the largest role
      for PCR may be in molecular fingerprinting. Arbitrary Primer PCR (RAPD) on the
      whole bacterial genome can reliably and accurately distinguish between isolates.
      PCR-based RFLP analysis can separate isolates based on restriction fragment sizes
      in a smaller amplified genome segment. REP-PCR can group isolates into clusters
      that appear to have different clinical expressions. These methods promise to shed
      new light on the transmission and pathogenicity of H. pylori.

PMID- 9037624
TI  - Laboratory diagnosis of hepatitis C.
AB  - In 1989 the hepatitis C virus was cloned, some 20 years after the first
      suggestion that hepatitis C virus(es) (HCV) existed. Since that time there has
      been rapid development of serological tests for detection of antibody to HCV and
      molecular tests for detection, quantitation, and characterization of HCV RNA. The
      development and performance characteristics of these test methods are reviewed
      and their implications for diagnosis, prognosis, and monitoring patients on
      therapy are discussed.

PMID- 9037623
TI  - The evolution of hantaviruses.
AB  - Hantaviruses exist in most regions of the world. The many different strains
      identified thus far have widely divergent roles in human disease and infect a
      wide range of rodent hosts. The sequence data available for the genomes of these
      viruses allows us to study indirectly the evolutionary patterns of the
      hantaviruses. In this paper, we describe relationships among the M genomic
      segments of hantaviruses, and attempt to relate these to the evolutionary
      relationships of the virus' rodent hosts.

PMID- 9037625
TI  - Polymerase chain reaction assays for the detection of cytomegalovirus in organ
      and bone marrow transplant recipients.
AB  - Cytomegalovirus (CMV) infection is ubiquitous and results in a wide spectrum of
      clinical manifestations ranging from asymptomatic infection to severe life
      threatening disease. Infection in normal children and adults usually causes no
      symptoms but in the immunocompromised host, CMV may result in severe
      opportunistic infections with high morbidity and mortality. Historically, virus
      detection was dependent on culture of the virus or on a centrifugation culture
      system referred to as a shell vial assay. The shell vial assay frequently lacked
      sensitivity and was unable to detect infection in its early phase. Also, as with
      culture assays, the results were affected by antiviral therapy. The CMV
      antigenemia assay was developed to provide more rapid results and has gained wide
      usage. This assay is limited to detection of the virus in white blood cells and
      is more sensitive than culture or the shell vial assay. Application of the
      polymerase chain reaction (PCR) to these problems has resulted in the development
      of assays for CMV which are more sensitive than previously available methods.
      This method employs liquid hybridization with 32P labeled probes and gel
      retardation analysis for detection of amplified DNA specific for each virus. A
      comparison of the detection of CMV by an antigenemia assay or the PCR method in
      the leukocytes of renal transplant patients revealed that the PCR assay detects
      cytomegalovirus earlier and more consistently than the antigenemia assay.
      Finally, the application of a fluorescent dye detection system and image analysis
      of the acrylamide gel with a laser scanner provides additional sensitivity to the
      detection of cytomegalovirus, as well as avoiding the use of radioactivity,
      making the assay more adaptable to the clinical laboratory.

PMID- 9037626
TI  - HTLV-associated diseases: human retroviral infection and cutaneous T-cell
      lymphomas.
AB  - An array of neurologic, oncologic, and autoimmune disorders are associated with
      infection with the human pathogenic retroviruses human T-cell leukemia virus
      types I and II (HTLV-I, II), as well as the human immunodeficiency viruses (HIV).
      The cutaneous T-cell lymphomas, mycosis fungoides (MF) and its hematogenous
      variant Sezary Syndrome (SS), share similar clinical and pathological features to
      HTLV-I-associated adult T-cell leukemia (ATL) and speculation of a retroviral
      link to MF and SS, especially in areas non-endemic for ATL, has lead to an
      intensified search for HTLV- and HIV-like agents in these diseases. To further
      explore a potential role for human retroviruses in MF and SS, skin biopsy-derived
      or peripheral blood mononuclear cell-derived DNA from 17 patients (MF, n = 7;
      erythrodermic MF (EMF), n = 5; SS, n = 5) from the North Eastern United States
      were screened using gene amplification by PCR and a liquid hybridization
      detection assay. Previously published primers and probes for HTLV-I (LTR, gag,
      pol, env, and pX), and our own primers and probes for HTLV-I (gag, pol, and env),
      HTLV-II (pol and env) and HIV-I (gag and pol) were employed. Serum antibodies to
      HTLV-I were negative in all but one EMF patient. The single HTLV-I seropositive
      patient carrying a diagnosis of EMF generated positive amplified signals for all
      of the eight HTLV-I regions tested. Ultimately, this individual evolved to
      exhibit clinical manifestations indistinguishable from ATL. The other 16 patients
      were negative for all 12 HTLV and HIV retroviral regions. Our findings suggest
      that none of the known prototypic human retroviruses are associated with
      seronegative MF and SS. The uniformly positive results for HTLV-I in the
      seropositive patient suggests that this patient initially presented with a
      smoldering form of ATL and illustrates the difficulty that sometimes may be
      encountered in the differential diagnosis of MF, SS, and ATL based solely on
      clinical and histopathological criteria.

PMID- 9037627
TI  - Management of cytomegalovirus infection in solid-organ transplant recipients.

PMID- 9037628
TI  - Immunodiagnosis of prion disease.
AB  - The immunodiagnosis of prion diseases is of critical importance due to the
      transmissibility of these conditions and their fatal prognosis. A panel of
      monoclonal and polyclonal antibodies have been generated for use in the study and
      diagnosis of these diseases. This manuscript describes the generation and
      characterization of these antibodies as well as their diagnostic application.

PMID- 9037629
TI  - Chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) has emerged as a public health concern over the
      past decade. A working case definition was created in 1988 and revised in 1994,
      and this has been used to establish prevalence estimates using physician-based
      surveillance and an a random digit dial telephone survey. Although CFS has some
      characteristics of an infectious disease, so far no infectious agent has been
      associated with the illness. Studies of immune function in CFS patients failed to
      detect differences between cases and healthy controls. However, when cases were
      subgrouped according to whether they had a sudden or gradual onset, differences
      in immunologic markers were detected between cases and their matched controls.

PMID- 9037630
TI  - Superantigens: their role in infectious diseases.
AB  - In the last 10 years many of the superantigens of the microbial world have been
      defined and the mechanisms of cellular interaction between lymphocytes and
      antigen presenting cells has been elucidated in great detail. The consequences of
      superantigen stimulation of the immune system, though less well defined, can be
      considered in three separate stages: T-cell proliferation, apoptosis, and
      recovery. Understanding these stages may explain why diverse superantigens may
      cause markedly different clinical processes ranging from acute shock to chronic
      arthritis and may form the basis for novel treatments of these diverse diseases.

PMID- 9037631
TI  - Searching for superantigens.
AB  - Superantigens comprise a large group of viral and bacterial proteins that
      stimulate T lymphocyte proliferation without regard for the antigenic specificity
      of the T cells but dependent on the composition of the variable part of the beta
      chain of the T cell receptor. Superantigens induce T cell proliferation dependent
      on class II MHC molecules on antigen presenting cells but do not require
      processing. Major subfamilies of superantigens include the viral superantigens,
      the bacterial pyrogenic toxin superantigens, and other bacterial superantigens.
      Two major approaches have been taken to identify superantigen association with
      human diseases: a) assessing V beta T cell receptor skewing in peripheral blood
      or tissues of patients with illnesses, b) recognition of toxic shock syndrome and
      related illnesses which are likely to be caused by superantigens.

PMID- 9037632
TI  - Is G-CSF safe and useful in the treatment of infectious diseases in the non
      neutropenic host?

PMID- 9037633
TI  - Gastric tonometry: does it work?

PMID- 9037634
TI  - Lung imaging in the adult respiratory distress syndrome: current practice and new
      insights.

PMID- 9037636
TI  - Candidemia in non-neutropenic critically ill patients: analysis of prognostic
      factors and assessment of systemic antifungal therapy. Study Group of Fungal
      Infection in the ICU.
AB  - OBJECTIVE: To determine the incidence and prognosis of candidemia in non
      neutropenic critically ill patients, to define mortality-related factors, and to
      evaluate the results of systemic antifungal therapy. DESIGN: A prospective
      multicenter survey in which medical and/or surgical intensive care units (ICUs)
      in 28 hospitals in Spain participated. PATIENTS: All critically ill patients with
      positive blood cultures for Candida species admitted to the participating ICUs
      over a 15-month period were included. INTERVENTIONS: Candidemia was defined as
      the presence of at least one positive blood culture containing Candida species.
      The follow-up period was defined as the time elapsed from the first positive
      blood culture for Candida species to discharge or death during hospitalization.
      Antifungal therapy was considered to be "early" when it was administered within
      48 h of the date when the first positive blood culture was obtained and "late"
      when it was administered more than 48 h after the first positive blood culture.
      MEASUREMENTS AND MAIN RESULTS: Candidemia was diagnosed in 46 patients (mean age
      59 years), with an incidence of 1 critically ill patient per 500 ICU admissions.
      The species most frequently isolated were Candida albicans (60%) and C.
      parapsilosis (17%). Fluconazole alone was given to 27 patients, amphotericin B
      alone to 10, and sequential therapy to 6. Three patients did not receive
      antifungal therapy. The overall mortality was 56% and the attributable mortality
      21.7%. In the univariate analysis, mortality was significantly associated with a
      higher Acute Physiology and Chronic Health Evaluation (APACHE) II score at the
      onset of candidemia (p = 0.04) and with the time elapsed between the episode of
      candidemia and the start of antifungal therapy 48 h or more later (p < 0.02).
      Patients with an APACHE II score lower than 21 at the onset of candidemia had a
      higher probability of survival than patients who were more seriously ill (p =
      0.04). Patients with "early" antifungal therapy (< or = 48 h between the onset of
      candidemia and the start of antifungal therapy) had a higher probability of
      survival compared with patients with late therapy (p = 0.06). No significant
      differences were noted between the two groups on different antifungal therapy.
      CONCLUSIONS: The incidence of candidemia in ICU patients was very low. An APACHE
      II score > 20 at the time of candidemia was associated with a higher mortality.
      Further studies with a large number of patients are needed to assess the effect
      of early antifungal therapy on the decrease in mortality associated with
      candidemia and to determine the appropriate dosage of fluconazole and duration of
      treatment.

PMID- 9037635
TI  - Safety of a low-dosage Filgrastim (rhG-CSF) treatment in non-neutropenic surgical
      intensive care patients with an inflammatory process.
AB  - OBJECTIVE: To evaluate the effect and safety of a low dose Filgrastim treatment
      in surgical intensive care patients. DESIGN: Prospective, clinical study.
      SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS:
      Ten patients with the systemic inflammatory response syndrome (SIRS) and ten
      patients with sepsis were included in the study. INTERVENTIONS: Filgrastim was
      given intravenously at 1.0 microgram/kg for 3 days, followed by 0.5 microgram/kg
      for 4 days. MEASUREMENTS AND RESULTS: Filgrastim treatment increased leukocyte
      counts and plasma levels of G-CSF. Cytokine levels (IL-6 and IL-8) decreased in
      the first 3 days of treatment. None of the SIRS patients developed sepsis or
      multiple organ failure and none of the patients died. In the sepsis group four
      patients died. No adverse side effects were observed, especially no attenuation
      of lung injury. CONCLUSIONS: Low-dosage Filgrastim treatment in ICU patients is
      safe. Whether the observed changes of the inflammatory response can be attributed
      to Filgrastim has to be clarified in further randomized trials.

PMID- 9037637
TI  - The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in
      patients with septic shock.
AB  - OBJECTIVE: To assess the effects of low-dose dopamine on splanchnic blood flow
      and splanchnic oxygen uptake in patients with septic shock. DESIGN: Prospective,
      controlled trial. SETTING: University hospital intensive care unit. PATIENTS: 11
      patients with septic shock, diagnosed according the criteria of the 1992 American
      College of Chest Physicians/Society of Critical Care Medicine consensus
      conference, who required treatment with norepinephrine. MEASUREMENTS AND MAIN
      RESULTS: Systemic and splanchnic hemodynamics and oxygen transport were measured
      before and during addition of low-dose dopamine (3 micrograms/kg per min). Low
      dose dopamine and a marked effect on total body hemodynamics and oxygen
      transport. The fractional splanchnic flow at baseline ranged from 0.15 to 0.57.
      In 7 patients with a fractional splanchnic flow less than 0.30, low-dose dopamine
      increased splanchnic flow and splanchnic oxygen delivery and oxygen consumption.
      In 4 patients with a fractional splanchnic flow above 0.30, low-dose dopamine did
      not appear to change splanchnic blood flow. CONCLUSION: Low-dose dopamine has a
      potential beneficial effect on splanchnic blood flow and oxygen consumption in
      patients with septic shock, provided the fractional splanchnic flow is not
      already high before treatment.

PMID- 9037638
TI  - Continuous venovenous haemofiltration using polyacrylonitrile filters does not
      activate contact system and intrinsic coagulation pathways.
AB  - OBJECTIVES: To investigate whether continuous venovenous haemofiltration using
      polyacrylonitrile filters causes activation of the contact system and intrinsic
      coagulation pathways and if this, and/or low plasma levels of endogenous
      anticoagulants, influences filter lifespan. DESIGN: Observational study. SETTING:
      University Teaching Hospital Intensive Care Unit. PATIENTS: Twelve critically ill
      patients with acute renal failure receiving continuous venovenous
      haemofiltration. INTERVENTIONS: Blood samples were taken before starting
      haemofiltration, at 15 min, 1 h, 3-4 h, 8-12 h, 24 h and at 24-h intervals
      thereafter until filter blockage occurred. Measurement was made of the contact
      and intrinsic coagulation system proteins factor XII, activated factor XII and
      prekallikrein and the protease inhibitors antithrombin III, heparin co-factor II,
      alpha 2-macroglobulin and C1-esterase inhibitor. Thrombin-antithrombin complex
      levels were measured to provide evidence of thrombin generation. RESULTS: (i)
      Factor XII, prekallikrein and contact system inhibitors were subnormal in 10/12
      and activated factor XII raised in 11/12 patients at baseline, implying pre
      existing contact pathway activation. (ii) No change occurred during
      haemofiltration in the intrinsic coagulation pathway factor or inhibitor levels.
      (iii) Clotting of the filter circuit within the first 24 h occurred in 5/12 and
      was associated with low baseline levels of antithrombin III and heparin co-factor
      II. Only in these patients did thrombin-antithrombin complex levels rise
      significantly. CONCLUSIONS: The contact system was not activated further by
      continuous venovenous haemofiltration using polyacrylonitrile filters in
      critically ill patients. Premature clotting of the haemofilter circuit was more
      common in patients with very low levels of antithrombin III and heparin co-factor
      II; although this was related to thrombin generation, the intrinsic coagulation
      pathway does not appear to be implicated.

PMID- 9037639
TI  - Plasma exchange for treatment of thrombotic thrombocytopenic purpura in
      critically ill patients.
AB  - OBJECTIVE: Description of diagnostic procedures, treatment modalities and
      intensive care management of patients with thrombotic thrombocytopenic purpura
      (TTP). DESIGN: Descriptive study. SETTING: Internal medicine Intensive Care Unit
      (University Hospital of Vienna). PATIENTS: Six patients (two after allogeneic
      bone marrow transplantation), treated for 12 episodes of TTP. INTERVENTIONS:
      Treatment with plasma exchange (fresh frozen plasma, 50-80 ml/kg per day),
      prednisone (0.75 mg/kg b.i.d.) and, in some cases, vincristine. Supportive
      therapy as needed. MEASUREMENTS AND RESULTS: Patients were admitted to the ICU
      because of neurological symptoms with acute onset (42% mild, 58% severe),
      hemolysis and thrombocytopenia. Additional symptoms were fever (50%), bleeding
      tendency (50%), acute renal failure (42%) and metabolic derangement (8%). Initial
      laboratory values showed thrombocytopenia (median 17 G/l), hemolysis (median
      hemoglobin 10.0 g/dl, lactate dehydrogenase 635 U/l, reticulocyte count 175 G/l)
      with red cell fragmentation. Coagulation tests were normal. Respiratory assist
      was needed in six episodes (severe seizures, cardiopulmonary resuscitation). In
      patients without preexisting hematological abnormality the platelet counts
      exceeded 100 G/l after 3-8 cycles of plasma exchange. In patients after bone
      marrow transplantation, the platelet counts never exceeded 40 G/l, but the
      lactate dehydrogenase levels dropped significantly. The neurological symptoms
      disappeared in all patients and renal function normalized. One patient died
      before the initiation of therapy. Three patients relapsed 1-3 times between 2
      weeks and 5 months after the last episode. The relapses were associated with
      symptoms similar to the first episode and responded promptly to plasma therapy.
      CONCLUSIONS: TTP is a rare, but life-threatening disorder. It needs immediate
      diagnosis and has a good prognosis after adequate treatment with plasma exchange.

PMID- 9037640
TI  - Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients
      with the acute respiratory distress syndrome and in hypoxemic patients with
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Inhalation of nitric oxide (NO) can improve oxygenation and decrease
      mean pulmonary artery pressure (MPAP) in patients with the acute respiratory
      distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar
      effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD).
      DESIGN: Prospective clinical study. SETTING: General intensive care unit in
      Sabadell, Spain. PATIENTS: Nine mechanically ventilated COPD patients (mean age
      72 +/- 2 years; forced expiratory volume in 1 s 0.91 +/- 0.11 l) and nine ARDS
      patients (mean age 57 +/- 6 years; mean lung injury score 2.8 +/- 0.1).
      MEASUREMENTS AND RESULTS: We measured hemodynamic and gas exchange parameters
      before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20
      min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group,
      these parameters were measured before NO inhalation (basal 1), during different
      doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued
      (basal 2). A positive response to NO was defined as a 20% increment in basal
      arterial partial pressure of oxygen (PaO2). MPAP and pulmonary vascular
      resistance (PVR) decreased significantly, while other hemodynamic parameters
      remained unchanged after NO-10 in both groups. Basal oxygenation was higher in
      the COPD group (PaO2/FIO2 (fractional inspired oxygen) 190 +/- 18 mmHg) than in
      the ARDS group (PaO2/FIO2 98 +/- 12 mmHg), (p < 0.01). After NO-10, PaO2/FIO2
      increased (to 141 +/- 17 mmHg, p < 0.01) and Qva/Qt decreased (39 +/- 3 to 34 +/-
      3%, p < 0.01) in the ARDS group. There were no changes in PaO2/FIO2 and Qva/Qt
      when the NO concentration was increased to 30 ppm in the COPD group. In both
      groups, a correlation was found between basal MPAP and basal PVR, and between the
      NO-induced decrease in MPAP and in PVR. The NO-induced increase in PaO2/FIO2 was
      not correlated with basal PaO2/FIO2. In the ARDS group, six of the nine patients
      (66%) responded to NO and in the COPD group, two of nine (22%) (p = 0.05).
      CONCLUSIONS: NO inhalation had similar effects on hemodynamics but not on gas
      exchange in ARDS and COPD patients, and this response probably depends on the
      underlying disease.

PMID- 9037641
TI  - Effects of nebulized salbutamol on respiratory mechanics in adult respiratory
      distress syndrome.
AB  - OBJECTIVE: To determine whether nebulized salbutamol improves the respiratory
      mechanics of patients with adult respiratory distress syndrome (ARDS). We also
      assessed the mechanisms that contribute to high respiratory system resistances
      during this disease. PATIENTS AND SETTING: Eleven consecutive patients with ARDS
      without clinical evidence of chronic obstructive pulmonary disease, admitted to a
      polivalent intensive care unit, and mechanically ventilated with Siemens Elema
      Servo C ventilator at constant inspiratory flow. METHOD: Peak airway pressure
      (Ppeak), airway pressure immediately after end inspiratory occlusion (P1),
      plateau pressure (P2) and intrinsic positive end-expiratory pressure (PEEPi) were
      measured at baseline condition and then 5, 15, and 30 min after 1 mg of
      salbutamol had been administered via a nebulizer through the endotracheal tube.
      Partial pressure of arterial oxygen (PaO2), heart rate (HR) and mean blood
      pressure (BP) were monitored and minimal respiratory system resistances (Rrs, m),
      additional resistances (DRrs) and static compliance (Cst) were computed. RESULTS:
      Between baseline and post-salbutamol, we observed changes in Ppeak, P1, P2, PEEPi
      and Rrs, m. As there were no significant differences between values at the
      different intervals during post administration, the results are described
      comparing baseline and 15 min post-salbutamol administration values. We found a
      significant decrease in Ppeak (4.9 +/- 0.8 cmH2O). P1 (3 +/- 0.6 cmH2O). P2 (2.1
      +/- 0.6 cmH2O), PEEPi (1.9 +/- 0.5 cmH2O) and Rrs, m (1.9 +/- 0.3 cmH2O/1 s-1);
      DR, rs decreased in five patients, did not change in four and increased in two.
      HR, PaO2 and BP did not change. CONCLUSIONS: a) Salbutamol administered through
      the endotracheal tube by a nebulizer device lessens respiratory system
      resistances and airway and alveolar pressures, and therefore could decrease the
      risk of barotrauma and alveolar damage; b) high respiratory system resistances in
      ARDS have an increased smooth muscle tone component that can be reversible with
      salbutamol.

PMID- 9037642
TI  - Normal values of SvO2 as therapeutic goal in patients with multiple injuries.
AB  - OBJECTIVE: To determine whether maintaining normal levels of mixed venous oxygen
      saturation (SvO2) in patients with multiple injuries is more relevant to survival
      than maintaining above-normal levels of oxygen transport. DESIGN: Non-randomised,
      retrospective control study over a 38-month period. SETTING: Multidisciplinary
      intensive care unit in a university hospital. PATIENTS: 40 patients with multiple
      injuries divided in to group A (23 patients) and group B (17 patients).
      INTERVENTIONS: In group A patients, we maintained normal SvO2 by manipulation of
      oxygen transport variables: oxygen delivery (DO2) was increased only if SvO2
      decreased or the dobutamine test was positive. In group B patients, DO2 was
      routinely maintained at above-normal levels by aggressive use of fluids and
      dobutamine. MEASUREMENTS AND RESULTS: In group A we measured SvO2 continuously
      and performed the dobutamine test. Oxygen transport-related variables were
      recorded every 12 h in the first 5 days after injury in both groups, as well as
      lactate concentrations. Survival was significantly greater in group A than in
      group B (p < 0.01). Multiple organ failure was less frequent in group A than in
      group B (p < 0.01). The average DO2 in group A was significantly lower than in
      group B from day 2 onwards (p < 0.05-0.01). Average values of DO2 of 605-688 ml/
      min per m2 were required to maintain normal SvO2 and aerobic metabolism in group
      A; 10 patients required dobutamine 2.5-5 micrograms/kg per min. The average DO2
      in group B was 622 ml/ min per m2 on day 1 and then it increased to 835 ml/min
      per m2 on day 5 after trauma. CONCLUSIONS: Our results indicate that for patients
      with multiple injuries maintaining normal SvO2 values and increasing DO2 only if
      required are more relevant for survival than routine maintenance of above-normal
      oxygen transport values.

PMID- 9037643
TI  - Platelet activation with massive formation of thromboxane A2 during and after
      cardiopulmonary resuscitation.
AB  - OBJECTIVE: Hypoxia and ischemia cause endothelial cell damage with consequent
      platelet activation. The hypothesis that human cardiac arrest accelerates
      platelet activation and the formation of prostanoids was tested. DESIGN:
      Prospective, observational cohort study. SETTING: Emergency Department and
      general Intensive Care Unit in a city hospital. INTERVENTIONS: Basic and advanced
      life support. PATIENTS AND PARTICIPANTS: Forty-seven out-of-hospital cardiac
      arrest patients. The patients were classified into two groups, those who were
      resuscitated (n = 18) and those who died (n = 29). MEASUREMENTS AND RESULTS:
      Serial levels of platelet aggregation, thromboxane B2 (TXB2), 11-dehydro-TXB2 and
      6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured. The results of
      measurements and demographic data were compared between the groups. Platelet
      counts decreased at the end of cardiopulmonary resuscitation (CPR), the decrease
      of the platelet counts showed statistical significance especially in the patients
      who died (p < 0.001). Platelet aggregation induced by adenosine diphosphate,
      epinephrine and collagen decreased to the lower limits of normal during and after
      CPR. Although high values of TXB2 and 11-dehydro-TXB2 continued throughout the
      study period in the resuscitated patients, 6-keto-PGF1 alpha decreased to the
      normal range (22.7 +/- 3.6 pg.ml-1. p < 0.05 at -24 h after arrival at the
      Emergency Department. CONCLUSIONS: Platelet activation with the massive formation
      of thromboxane A2 (TXA2) occurs in patients with out-of-hospital cardiac arrest.
      Successful resuscitation is not associated with the balanced production of PGI2
      against the TXA2 formation.

PMID- 9037644
TI  - Comparison of the APACHE III, APACHE II and Glasgow Coma Scale in acute head
      injury for prediction of mortality and functional outcome.
AB  - OBJECTIVES: This study examines the efficacy of the predicting power for hospital
      mortality and functional outcome of three different scoring systems for head
      injury in a neurosurgical intensive care unit (NICU). DESIGN: On the day of
      admission, data were collected from each patient to compute the Acute Physiology,
      Age, and Chronic Health Evaluation (APACHE) II and III, and Glasgow Coma Scale
      (GCS) scores. Hospital mortality was defined as the deaths of patients before
      discharge from hospital. Early mortality was defined as death before the 14th day
      after admission. Late mortality was defined as death after the 15th day from
      admission. Functional outcome was evaluated by Index of Independence in
      Activities of Daily Living (Index of ADL). SETTING: An 8-bed NICU in a 1270-bed
      medical center in Taichung Veterans General Hospital. PATIENTS AND PARTICIPANTS:
      Two hundred non-selected patients with acute head injury were included in our
      study in a consecutive period of 2 years. Patients less than 14 years old were
      not included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Sensitivity,
      specificity and correct prediction outcome were measured by the chi-square method
      in three scoring systems. The Youden index was also obtained. The best cut-off
      point in each scoring system was determined by the Youden index. The difference
      in Youden index was calculated by Z score. A difference was also considered if
      the probability value was less than 0.05. The area under Receiver Operating
      Characteristic (ROC) curve was computed. Then the area under ROC of each scoring
      system was compared by Z score. There was statistical significance if p was less
      than 0.05. For prediction of hospital mortality, the best cut-off points are 55
      for APACHE III, 17 for APACHE II and 5 for GCS. The correct prediction outcome is
      82.4% in APACHE III, 78.4% in APACHE II and 81.9% in the GCS. The Youden index
      has best cut-off points at 0.68 for APACHE III 0.59 for APACHE II, and 0.56 for
      GCS. The area under Receiver Operating Characteristic (ROC) curve is 0.90 in the
      APACHE III, 0.84 in the APACHE II and 0.86 in the GVS. There are no statistical
      differences among APACHE III and II, and GCS in terms of correct prediction
      outcome, Youden Index and the area under the ROC curve. Other physiological
      variables excluding GCS in APACHE III and II (AP III-GCS, AP II-GCS) have less
      statistical value in the determination of mortality for acute head injury. For
      the prediction of late mortality, APACHE III and II yield significantly better
      results in the area under the ROC curve, correct prediction and Youden index than
      those of GCS. Other physiological variables (AP III-GCS and AP II-GCS) play an
      important role in the prediction of late mortality in APACHE scores. For
      prediction of the functional outcome of surviving patients with acute head
      injury, the APACHE III yields the best results of correct prediction outcome,
      Youden index and the area under the ROC curve. CONCLUSION: The APACHE III and II
      may not replace the role of GCS in cases of acute head injury for hospital or
      early mortality assessment. But for prediction of the late mortality, the APACHE
      III and II have better accuracy than GCS. Other physiological variables excluding
      GCS in the APACHE system play a crucial contribution for late mortality. GCS is
      simple, less time-consuming and economical for patients with acute head injury
      for the prediction of hospital and early mortality. The APACHE III provides
      better prediction for severe morbidity than GCS and APACHE II. Therefore, the
      APACHE III provides a good assessment not only for hospital and late mortality,
      but also for functional outcome.

PMID- 9037645
TI  - A cost analysis of a treatment policy of a deliberate perioperative increase in
      oxygen delivery in high risk surgical patients.
AB  - OBJECTIVE: To investigate the cost implications of a treatment policy of a
      deliberate perioperative increase of oxygen delivery in high risk surgical
      patients. DESIGN: A cost-effectiveness analysis comparing 'protocol' high risk
      surgical patients in whom oxygen delivery was specifically targeted towards 600
      ml/min/m2 with 'control' patients. INTERVENTIONS: In a randomised, controlled
      clinical trial we previously demonstrated a significant reduction in mortality
      (5.7% vs 22.2%, p = 0.015) and morbidity (0.68 +/- 0.16 complications vs 1.35 +/-
      0.20, p = 0.008) in 'protocol' high risk surgical patients in whom oxygen
      delivery was specifically targeted towards 600 ml/min per m2 compared with
      'control' patients. This current study retrospectively analysed the medical care
      and National Health Service resource use of each patient in the trial.
      Departmental purchasing records and business managers were consulted to identify
      the unit cost of these resources, and thereby the cost of treating each patient
      was calculated. RESULTS: The median cost of treating a protocol patient was lower
      than for a control patient (6,525 pounds vs 7,784 pounds) and this reduction was
      due mainly to a decrease in the cost of treating postoperative complications
      (median 213 pounds vs 668 pounds). The cost of obtaining a survivor was 31% lower
      in the protocol group. CONCLUSION: Perioperative increase of oxygen delivery in
      high risk surgical patients not only improves survival, but also provides an
      actual and relative cost saving. This may have important implications for the
      management of these patients and the funding of intensive care.

PMID- 9037646
TI  - Occlusive mesenteric ischemia and its effects on jejunal intramucosal pH,
      mesenteric oxygen consumption and oxygen tensions from surfaces of the jejunum in
      anesthetized pigs.
AB  - OBJECTIVE: To investigate the effects of superior mesenteric artery (SMA) flow
      reduction on the jejunal intramucosal pH (pHi) and to compare these effects with
      corresponding changes of mesenteric oxygen transport variables and oxygen
      tensions on the surfaces of the jejunal serosa and mucosa. DESIGN: Prospective,
      randomized, controlled, experimental study. SETTING: Animal research laboratory.
      SUBJECTS: 20 domestic pigs. INTERVENTIONS: Mechanical flow reduction in the SMA.
      The animals were randomized to have an SMA flow of 0%, 25%, 38%, 50% or 100%
      (control). MEASUREMENTS AND MAIN RESULTS: Measurements (baseline, ischemia,
      reperfusion) consisted of hemodynamic and oxygen transport variables, SMA blood
      flow, mesenteric oxygen transport variables, pHi and oxygen tensions of the
      jejunal serosa and mucosa. Flow reduction in the SMA resulted in a significant
      decrease of pHi indicating ischemia earlier than mesenteric oxygen transport
      variables. The relationship between mesenteric oxygen delivery (DO2ms) and pHi
      during acute ischemia is best described by a sigmoid curve. There was a linear
      correlation between the changes of the jejunal surface oxygen tensions and pHi
      due to SMA flow reduction. CONCLUSION: The sigmoid relationship between pHi and
      DO2ms indicated that pHi is a sensitive parameter for detecting ischemia at 50%
      of the baseline oxygen delivery and that below 25% there was no further decrease
      of pHi. In contrast, mesenteric and whole body oxygen transport parameters were
      not indicative of impaired mucosal oxygen supply.

PMID- 9037647
TI  - Accuracy of infrared ear thermometry in adult patients.
AB  - OBJECTIVE: To assess (1) the agreement between infrared ear thermometry and core
      reference temperature (in the pulmonary artery). (2) the agreement between
      measurements in the right and left ears, and (3) the screening validity of
      infrared tympanic thermometry in detecting rectal fever. DESIGN: Temperatures
      were measured in both ears with an infrared thermometer, in one group of patients
      by simultaneous measurements with thermistors inserted in the pulmonary artery,
      esophagus, and rectum, and in the other group with a rectal glass-mercury
      thermometer. SETTING: An intensive care unit and a department of internal
      medicine in a secondary care hospital. PATIENTS AND PARTICIPANTS: Two samples: 16
      adult patients admitted to the intensive care unit and 103 consecutive patients
      admitted to the department of medicine. MEASUREMENTS: The major outcome measures
      were (a) the agreement between infrared ear thermometry and thermistor pulmonary
      artery temperature and (b) the sensitivity and specificity for detecting fever,
      using rectal measurement as reference. RESULTS: Both rectal and esophageal
      thermistor measurements showed better agreement with the pulmonary artery
      reference temperature than single ear tympanic thermometry. The sensitivity and
      specificity of ear thermometry for detecting fever (> or = 38.0 degrees C rectal
      reference) were 0.58 and 0.94, respectively. Double ear thermometry had a
      sensitivity of 0.61 and a specificity of 0.95, when using the mean value.
      CONCLUSIONS: Both rectal and esophageal thermistor measurements showed better
      agreement with pulmonary artery temperature than single ear themometry. Using the
      mean of two ear measurements improves the agreement and screening validity for
      detecting fever by rectal temperature. If temperature measurements are critical,
      esophageal measurements achieve excellent agreement with pulmonary artery
      temperatures.

PMID- 9037648
TI  - The effects of inverse ratio ventilation on intracranial pressure: a preliminary
      report.
AB  - OBJECTIVE: To determine the effects of pressure control inverse ratio ventilation
      [PC-IRV], as compared with volume controlled normal ratio ventilation [VC], on
      the intracranial pressure [ICP] of patients with severe head injury. DESIGN: A
      prospective study with unblinded intervention. SETTING: The Intensive Therapy
      Unit of a base hospital. PATIENTS AND PARTICIPANTS: Nine cases of head injury
      requiring mechanical ventilation and intracranial pressure monitoring were
      studied. INTERVENTIONS: Patients were twice transferred from VC (1:E ratio 1:2)
      to PC-IRV (1:E ratio 2:1). Firstly, tidal volume was maintained at an equal
      value. Secondly, end tidal CO2 was maintained at an equal value. No other changes
      were made to ventilation, vasopressor therapy or ICP control. MEASUREMENTS AND
      RESULTS: Measurements were taken of ICP, mean arterial pressure (MAP) end tidal
      CO2 and respiratory parameters. In the first observation, there were significant
      changes in peak inspiratory pressure (PIP), mean airway pressure (Paw) and
      intrinsic positive end expiratory pressure (PEEP) but not for ICP, end tidal CO2,
      MAP and cerebral perfusion pressure (CPP). The correlation between change in ICP
      and change in end tidal CO2 was r = -0.74. In the second observation there were
      significant changes in tidal volume, PIP, Paw and intrinsic PEEP but not for ICP,
      MAP and CPP. The correlation between the change in ICP and the change in Paw was
      insignificant. CONCLUSIONS: PC-IRV has a minimal net effect on ICP. Changes in
      ICP correlate more strongly with changes in CO2 than changes in Paw.

PMID- 9037649
TI  - Amino acid losses and nitrogen balance during slow diurnal hemodialysis in
      critically ill patients with renal failure.
AB  - OBJECTIVE: The effects of slow diurnal hemodialysis (slow HD) on amino acid
      losses and nitrogen balance were studied. DESIGN: Slow HD was conducted for 10 h
      during the day at the dialysate flow rate of 30 ml/min. The patients received
      total parenteral nutrition including 40 g of amino acids (6.08 g of nitrogen).
      The amino acid concentrations in plasma and dialysate were determined and the
      daily nitrogen balance was calculated from the urea nitrogen appearance.
      PATIENTS: Six critically ill patients with renal failure were entered into the
      study. RESULTS: Slow HD eliminated 48.5 +/- 4.4 mmol (6.2 +/- 0.6 g) of amino
      acids, representing 16% of the daily amino acid load. The estimated nitrogen
      balance was -2.3 +/- 1.3 g/day. Amino acid nitrogen lost in the dialysate was 1.0
      +/- 0.1 g, contributing 43% of the daily negative nitrogen balance. CONCLUSION:
      The amount of amino acid losses during slow HD should be taken into consideration
      when designing nutritional schedules for maintaining positive nitrogen balance in
      critically ill patients.

PMID- 9037650
TI  - Increased lactate/pyruvate ratio with normal beta-hydroxybutyrate/acetoacetate
      ratio and lack of oxygen supply dependency in a patient with fatal septic shock.
AB  - We report a case of fatal septic shock, with hyperlactatemia and blood cultures
      positive for Streptococcus pneumoniae, in a 70-year-old patient. On two occasions
      (5 days, and 2 days before the patient's death), the relationship between oxygen
      delivery (DO2) and consumption (VO2) was examined in conjunction with two
      presumed markers of tissue oxygenation: the lactate/pyruvate ratio (L/P), and the
      beta-hydroxybutyrate acetoacetate ratio (beta OHB/AcAc). Increasing DO2 by about
      30% ("oxygen flux test") failed to increase VO2. The beta OHB/AcAc ratio remained
      within normal limits, thus suggesting uncompromised tissue oxygenation at the
      hepatic level. The L/P ratio remained persistently above normal limits, thus
      suggesting actual organ or regional hypoxia. This case shows that during an
      overwhelming septic shock, the "oxygen flux test" can be negative, despite the
      presence of hyperlactatemia and of an increased L/P ratio suggestive of impaired
      tissue oxygenation.

PMID- 9037651
TI  - Intrapericardial fibrinolysis: a useful treatment in the management of purulent
      pericarditis.
AB  - Since the introduction of antibiotics into clinical practice, purulent
      pericarditis has become a rare disease. The major complication of the standard
      management for this condition is constrictive pericarditis. We report two cases
      of purulent pericarditis in which intrapericardial fibrinolysis was performed in
      order to minimize this complication. The first case was a 38-year-old man
      admitted to our intensive care unit (ICU) for management of constrictive
      pericarditis complicating purulent pericarditis diagnosed 17 days previously. The
      patient was treated with four intrapericardial injections of streptokinase
      (250,000 IU each). Fluid drainage and cardiac output were improved. No change in
      clotting parameters was noted. Pericardiectomy and esophagectomy were then
      performed for a diagnosis of esophageal neoplasm. The postoperative course was
      uneventful. The second case was a 16-year-old boy admitted with loss of
      consciousness due to cardiac tamponade. Percutaneous pericardiocentesis drained
      900 ml of cloudy fluid. Two intrapericardial injections were performed (day 1 and
      day 5) without any complication. Pericardial drainage was withdrawn on day 13 and
      the patient was discharged from ICU on the same day. Six months later, there was
      no evidence of constrictive pericarditis. Intrapericardial fibrinolysis appears
      to be safe and effective when prescribed rapidly in the course of purulent
      pericarditis.

PMID- 9037652
TI  - Liver inflammation and acute respiratory distress syndrome in a patient receiving
      hepatitis B vaccine: a possible relationship?
AB  - We describe a patient in whom clinical evidence of liver and lung dysfunction
      developed after he received the second dose of recombinant hepatitis B vaccine,
      despite no serologic evidence of viral hepatitis. However, liver biopsy specimens
      demonstrated both surface antigens and core antigens, possibly indicating silent
      hepatitis B virus infection. A search for an infective etiology for the patient's
      subsequent clinical deterioration in lung function did not yield pathogens:
      postmortem examination revealed evidence of immune complex-mediated organ injury
      in the liver, lungs, and kidneys.

PMID- 9037653
TI  - Serotonin syndrome due to an overdose of moclobemide and clomipramine. A
      potentially life-threatening association.
AB  - The serotonin syndrome is frequently characterized by minor neurologic
      manifestations that regress rapidly (such as confusion, tremor, ...). Many
      medications including tricyclic antidepressants, serotonin reuptake inhibitors,
      tryptophan and the association of monoamine oxidase inhibitors together with a
      serotoninergic agent have been implicated in this syndrome. In certain cases, and
      for poorly understood reasons, clinical manifestations can include circulatory
      collapse, malignant hyperthermia, convulsions and rhabdomyolysis. These forms are
      often fatal. Treatment, other than the withdrawal of the offending drug, is
      symptomatic. Dialysis may be of value in withdrawing the drug from the
      circulatory system. We report a patient with the serotonin syndrome of favorable
      outcome due to an overdose of moclobemide and clomipramine.

PMID- 9037654
TI  - Continuous quality improvement in the ICU: general guidelines. Task Force
      European Society of Intensive Care Medicine.

PMID- 9037655
TI  - Myopathy and ventilatory failure in severe sepsis.

PMID- 9037656
TI  - Fenthion suicide poisoning by subcutaneous injection.

PMID- 9037657
TI  - The use of the laryngeal mask airway in suitable ICU patients undergoing
      percutaneous dilational tracheostomy.

PMID- 9037658
TI  - Polymyxin B-immobilized fiber improves hyperdynamic state in MRSA septic
      patients.

PMID- 9037659
TI  - The expression "proof" is often misused by reviewers and authors.

PMID- 9037660
TI  - Effect of nasogastric suction and ranitidine on the calculated gastric
      intramucosal pH.

PMID- 9037661
TI  - Relationship of changes in cardiac output to changes in heart rate in medical ICU
      patients.

PMID- 9037662
TI  - The release of tumor necrosis factor alpha (TNF-alpha) by interferon gamma (IFN
      gamma) induced THP-1 cells stimulated with smooth lipopolysaccharide is inhibited
      by MAbs against HLA-DR and CD14 receptors on the effector cell.
AB  - Bacterial lipopolysaccharide (LPS) plays a central role in the pathogenesis of
      gram-negative sepsis and shock. The glycosylphoshatidyl inositol (GPI) anchored
      glycoprotein CD14 on mononuclear cells binds LPS, especially in the presence of
      an LPS binding serum protein, activating the production of pro-inflammatory
      cytokines, i.e. TNF-alpha. However, since GPI anchorage to the cell membrane
      lacks the intracellular signalling capacity, the existence of at least a second
      receptor has been postulated. In attempt to identify additional LPS receptors, we
      used the human myelomonocytic cell line THP-1. This undifferentiated cell line
      did not respond to LPS in terms of TNF-alpha release, but when induced with 250
      U/ml of IFN-gamma for 48 h, the cells released TNF-alpha (174 +/- 58.6 U/ml. L929
      cell bioassay) in response to 10 vg/ml of E. coli 0111 LPS, in the absence of
      serum. Blockade of either HLA-DR or CD14 receptors with specific MAbs did not
      reduce the amount of cytokine released. However, when both the receptors were
      sequentially blocked involved on the effector cells a remarkable inhibition of
      TNF-alpha release was observed (8.6 +/- 1.4). It seems therefore, that HLA-DR
      receptor may be with CD14 in triggering TNF-alpha release by IFN-gamma, induced
      THP-1 cells.

PMID- 9037663
TI  - Primary infection by HHV-6 variant B associated with a fatal case of
      hemophagocytic syndrome.
AB  - The association of a human herpesvirus 6 primary infection with a fatal case of
      hemophagocytic syndrome in a 3 month old baby is described. The trigger mechanism
      of the virus for the clinical syndrome is discussed.

PMID- 9037664
TI  - Productive HHV-6 infection in differentiated U937 cells: role of TNF alpha in
      regulation of HHV-6.
AB  - This study characterizes the effect of differentiation on the resistance of the
      human monocytic cell line U937 to human herpes virus type 6 (HHV-6). The use of
      monocytic cell line has the advantage of avoiding genetic variations among
      different donors. The HHV-6 infection was compared in undifferentiated U937 cells
      and U937 cells differentiated with a combination of vitamin D3 and retinoic acid.
      Undifferentiated U937 cells were highly resistant to HHV-6 infection.
      Differentiation of U937 cells was accompanied by an increase in permissiveness
      for HHV-6 demonstrated in terms of extracellular virus production and viral
      antigen positive immunofluorescent cells. Tumor necrosis factor alpha (TNF alpha)
      appears to be an essential mediator during the first line defences of the host
      against viruses, even though its role during viral infection remains
      controversial. For this reason we examined the behaviour of TNF alpha in
      differentiated U937 upon HHV-6 infection. No basal production of TNF alpha was
      found in culture supernatants, while HHV-6 infection up-regulated TNF alpha
      release. The addition of human recombinant-TNF alpha to HHV-6 infected cells
      induced a marked cytotoxic effect accompanied by an increased release of
      extracellular virus, whereas it did not affect viral replication, as shown by the
      unmodified percentage of antigen positive cells. In conclusion, TNF alpha acts as
      a soluble mediator of cytotoxicity against HHV-6 infected U937 cells, but it
      fails to induce an antiviral state.

PMID- 9037665
TI  - Alterations in the chemical composition of peptidoglycan of Escherichia coli DH5
      alpha induced by the expression of Enterococcus faecalis penicillin binding
      protein 5.
AB  - Low-affinity penicillin binding proteins (PBPs) are a particular class of
      membrane proteins involved in penicillin resistance in Enterococci and other
      micro-organisms. This PBP is thought to be capable of taking over the activity of
      all other PBPs during peptidoglycan synthesis. Unfortunately, nothing is known
      about the enzymatic activity catalyzed by this PBP, but a
      transpeptidase/transglycosylase action can be postulated to allow complete
      peptidoglycan synthesis. Recently, we cloned and expressed in Escherichia coli
      the PBP5 (a low-affinity PBP) of Enterococcus faecalis (Signoretto, C., Boaretti,
      M., and Canepari, P.: FEMS Microbiol. Lett. 123, 99-106, 1994). Here we describe
      some of the effects of this PBP when expressed in E. coli, in terms of increased
      growth rate and autolysis, and particularly its effects on the fine chemical
      composition of the E. coli peptidoglycan. A distinct increase in the di- and
      tripeptide monomers and a parallel decrease in the tetrapeptide monomer are
      described. The results presented here are explained in terms of a partial action
      of the postulated transpeptidase/ transglycosylase enzymatic complex which leads
      to the cleavage of one, two or three amino-acids from the pentapeptide monomer,
      but is incapable of performing the cross-linking between two side-chains due to
      lack of the natural substrate which is different from that of E. coli.

PMID- 9037666
TI  - One-tube nested polymerase chain reaction in the diagnosis of Chlamydia
      trachomatis infections.
AB  - A one-tube nested polymerase chain reaction (PCR) using primers derived from the
      major outer membrane protein gene sequence of Chlamydia trachomatis was compared
      with McCoy cell culture for the detection of the micro-organism in clinical
      specimens. Of 110 urogenital and ocular specimens, 21 were positive by culture
      and 25 by nested PCR; all 21 culture-positive specimens were also positive by
      nested PCR. After resolution of discrepant specimens as true-positive,
      sensitivity was 100% for nested PCR and 84% for cell culture, while specificity
      was 100% for both tests. One-tube nested PCR appears to be a rapid, highly
      sensitive and specific technique for diagnosing C. trachomatis infections.

PMID- 9037667
TI  - Evaluation of the in vitro activity of seven selected antimicrobial agents to be
      used for the isolation of human intestinal spirochaetes.
AB  - This study aimed at making a comparative assessment of the growth of pure
      cultures of Human Intestinal Spirochaetes (HIS) in a control medium without
      antibiotics and in media including antibiotics (spectinomycin, rifampin,
      colistin, polymyxin B, amphotericin B, vancomycin, spiramycin) whose use had been
      indicated in the literature in connection with the isolation of HIS or animal
      intestinal spirochaetes. All the strains of HIS tested grew in media to which
      appropriate concentrations of those drugs had been added giving a final number of
      CFU/ml +/- 10 times the number of CFU/ml observed in the control medium. These
      results indicate that a selective medium to be used for the isolation of HIS may
      include appropriate concentrations of one or more of the following antibiotics:
      spectinomycin (100-1,000 micrograms/ml), rifampin (10-30 micrograms/ml),
      vancomycin (6.25 micrograms/ml), colistin (6.25 micrograms/ml), polymyxin B (5
      micrograms/ml), spiramycin (1-10 micrograms/ml) and amphotericin B (0.05-35
      micrograms/ml).

PMID- 9037668
TI  - Comparative growth of pure cultures of human intestinal spirochaetes on six
      selective media.
AB  - The growth of pure cultures of 24 human intestinal spirochaetes (HIS) was
      analysed comparatively in six selective media with antibiotics and in a control
      medium without antibiotics. The selective media SR and SP were the only two media
      among the six tested which allowed the growth of all the strains studied. These
      media contained spectinomycin (400 micrograms/ml) and rifampin (30 micrograms/ml)
      (SR), and spectinomycin (400 micrograms/ml) and polymyxin B (5 micrograms/ml)
      (SP), respectively. Moreover, most of the strains tested showed in these two
      media a number of CFU/ml equal to, or, for a few strains, not more than ten-fold
      lower than that observed in the control medium. The other four selective media
      tested were: SRVC (spectinomycin 200 micrograms/ml; rifampin 12.5 micrograms/ml;
      vancomycin 6.25 micrograms/ml; colistin 6.25 micrograms/ml), CSp (colistin 6.25
      micrograms/ml; spiramycin 25 micrograms/ml), SRSp (spectinomycin 200
      micrograms/ml; rifampin 12.5 micrograms/ml; spiramycin 25 micrograms/ml) and
      SRVCSp (spectinomycin 200 micrograms/ml; rifampin 12.5 micrograms/ml; vancomycin
      6.25 micrograms/ml; colistin 6.25 micrograms/ml; spiramycin 25 micrograms/ml).
      The growth of most of the spirochaetes was strongly reduced in the media SRVC,
      CSp, SRSp and SRVCSp. Furthermore, several of the 24 HIS examined did not grow in
      the medium SRVC (3 spirochaetes, 11%), CSp (15 spirochaetes, 62%), SRSp (17
      spirochaetes, 70%), SRVCSp (19 spirochaetes, 79%). The results reported in this
      paper indicate that the media SR and SP, of the six selective media tested, may
      profitably be used in the isolation of HIS as they did not significantly affect
      the growth of the HIS tested.

PMID- 9037669
TI  - Effect of orthodontic therapy with fixed and removable appliances on oral
      microbiota: a six-month longitudinal study.
AB  - The present study evaluated microbiological and clinical changes occurring during
      the first six months of orthodontic therapy with fixed and removable appliances
      and the consequent risk for gingivitis and periodontal disease. This study was
      justified by the disagreement among different authors: only some of them reported
      gingivitis development and changes in dental plaque composition during
      orthodontic therapy with fixed appliances, others did not. Thirty, 7-to-15-year
      old children, fifteen with fixed and fifteen with removable appliances,
      previously motivated to oral hygiene, completed the study. They were clinically
      examined by a dentist at baseline and at the end of the study. Three supra and
      subgingival microflora samples were collected from the first molars, when the
      appliances were inserted (T0), 6-8 weeks later (T1) and 6-7 months later (T2).
      Microflora was examined using dark-field and light microscopes and cultural
      methods. An indicator of healthy status (percentage of Gram positive cocci in
      total bacterial count) and some risk indicators for gingivitis (bacterial count
      evaluated with light microscope, percentage of Gram negative rods) and for
      periodontitis (motile rod and spirochete percentages, presumptive Actinobacillus
      actinomycetemcomitans and Porphyromonas gingivalis prevalence) were investigated.
      Patients with fixed appliances were clinically healthy at T2; yet they showed
      significantly increased counts, motile rods, subgingival spirochetes and a
      decrease of Gram positive cocci. At T2, patients with removable appliances were
      clinically healthy and the only significant microbiological changes were
      supragingival motile rods and subgingival spirochetes. These data suggest that in
      the oral hygiene motivated patients of the present study, gingivitis and
      periodontitis do not occur, during the first six months of treatment: the
      significant modification of oral microbiota, shown by subjects with fixed
      appliances, however, suggests that the risk for gingivitis in the following
      months of therapy is still high and the risk for periodontitis cannot be
      excluded.

PMID- 9037670
TI  - In vitro virulence factors of Arcobacter butzleri strains isolated from
      superficial water samples.
AB  - Eighteen isolates of A. butzleri from river water samples were examined for their
      biotype, serogroup and putative virulence characteristics. Toxin profiles based
      on cytotonic, cytotoxic and cytolethal distending factors were determined after
      analysis responses in Vero and CHO cells Adhesivity and invasivity tests were
      performed on HeLa and Intestine 407 cells. Six biotypes and five serogroups were
      determined in our isolates. All strains but one induced cytotoxic effects on
      cells in culture. The cytotoxic negative strain caused elongation of CHO cells (a
      cytotonic-like effect). This strain was the only one which adhered to cells in
      vitro. Invasiveness was never observed. Our results show a phenotypic
      heterogeneity of arcobacters isolated from environmental sources, and indicate
      that some strains could be potentially virulent.

PMID- 9037671
TI  - Distribution and characterization of Bacillus thuringiensis in the environment of
      the olive in Greece.
AB  - The distribution of Bacillus thuringiensis in Greece, was studied and the
      presence of this organism was found in 11.2% of the samples collected. The
      characterization of the different isolates was based on their whole-cell protein
      profiles. Some of the isolates form quite unusual parasporal inclusions.

PMID- 9037672
TI  - Serological survey of leptospiral infections in sheep, goats and dogs in
      Cordillera province, Bolivta.
AB  - A serological survey for antibodies to Leptospira spp. was conducted on sheep,
      goat and dog serum samples collected in three localities in Cordillera province
      in the southern part of the Santa Cruz Department (Bolivia) in 1992. A total of
      98 sheep, 218 goats and 43 dogs were tested against 29 leptospiral serovars using
      the microscopic agglutination test. At the time of blood collection all of the
      examined animals appeared healthy and presented no clinical sign suggestive of
      leptospirosis. Antibody prevalences, as determined by positive results at a 1:100
      dilution or higher, was 14.3% in sheep, 19.7% in goats, and 14.0% in dogs.
      Agglutinins against six serovars (poi. shermani, pomona, canicola, javanica,
      djasiman) were found in positive animals. The highest serological prevalence in
      sheep and goats was recorded for serovar poi, followed by pomona in sheep and
      shermani in goats. Titres to shermani were the commonest in dogs. The results of
      this survey indicate that leptospiral infection is common in south-east Bolivia
      and that serovars of several serogroups concur in the etiology.

PMID- 9037673
TI  - Lymphogranuloma venereum: a case report in an Italian traveller.
AB  - A 38-year-old man with a recent history of travel in India and unprotected sexual
      intercourse with Indian women, was admitted with painful enlarged lymphnodes
      predominantly in the right inguinal area. Diagnosis of lymphogranuloma venereum
      was made by means of a positive immunofluorescence test (Total Ig titer of 1:512)
      and a positive detection of chlamydial antigens by ELISA in a semen sample. He
      was successfully treated with ciprofloxacin. This observation emphasizes the
      relevance of infection due to C. trachomatis serotypes L1-L3 that may be acquired
      during travel in developing countries.

PMID- 9037674
TI  - Detection of genotype 4 hepatitis C virus (HCV) in Italy.

PMID- 9037675
TI  - Beneficial use of inactivated porcine adenovirus vaccine and antibody response of
      young pigs.
AB  - An inactivated adenovirus vaccine experimentally prepared was inoculated into
      young pigs against the adenovirus infection newly appeared in Japan. Sero
      neutralizing titers of the paired sera collected from 50 pigs in the interval of
      3 weeks was measured. The mean of antibody titers of post-sera was 45 times
      higher than that of pre-sera.

PMID- 9037676
TI  - [Diagnostic imaging of the orthopaedic diseases with special emphasis on magnetic
      resonance technology].

PMID- 9037677
TI  - [Clinical significance of heavy particle therapy for malignant tumor of the bone
      and soft tissues].

PMID- 9037678
TI  - [Tiny studies for occupational disorders].

PMID- 9037679
TI  - Preoperative scintigraphic and intraoperative scintimetric localization of
      parathyroid adenoma with cationic Tc-99m complexes and a hand-held gamma-probe.
AB  - AIM: The aim of our study was to evaluate the possibility of intraoperative
      scintimetric detection of parathyroid adenomas with Tc-99m labelled tracers for
      its usefulness in dystropic or ectopic adenomas. METHODS: 12 women with
      biochemically confirmed hyperparathyroidism were included in our study. After
      injection of 370 MBq Tc-99m tetrofosmin e.g. sestamibi, preoperative scintigraphy
      (double phase study and SPECT) was performed and T/NT ratios were evaluated for
      early, delayed and SPECT images. Surgery was performed using a hand-held gamma
      probe after preoperative injection of 555-925 MBq Tc-99m tetrofosmin e.g.
      sestamibi. Count rates (cts/10 sec) were measured and used for calculating in
      situ- and ex situ-T/NT ratios. RESULTS: In 9 out of 12 patients, adenoma could be
      detected on static images. Mean T/NT ratios for Tc-99m tetrofosmin were 1.29 for
      early and 1.23 for delayed images, respectively 1.39 and 1.23 for early and
      delayed Tc-99m sestamibi scan. Three cases could only be detected with SPECT
      reconstruction, 11 of 12 parathyroid adenomas could be confirmed intra
      operatively. CONCLUSION: SPECT with Tc-99m labelled cationic complexes showed
      advantages in detection, precise localization and contrast over static
      scintigraphy and should therefore be performed at least in cases with poor or no
      uptake on static images to avoid failures in detection of deeply sited,
      dislocated glands or adenomas with low uptake. Intraoperative localization and
      confirmation of parathyroid adenoma with Tc-99m labelled cationic complexes and a
      gamma probe is possible an 1 may be useful in case of dys- or ectopic adenoma by
      influencing surgical approach and operating time.

PMID- 9037680
TI  - Layer performance of four strains of Leghorn pullets subjected to various rearing
      programs.
AB  - Two experiments were conducted using four strains of Leghorn pullets, namely
      Babcock, DeKalb, H & N, and Shaver. Pullets were grown on conventional or low
      protein diets fortified with additional amino acids. At 18 wk of age, 64 pullets
      from each strain and diet treatment were transferred to individual laying cages,
      using eight replicate groups of four adjacently caged birds. In a second
      experiment, pullets from the four strains were selected based on body weight at
      18 wk of age (approximately 1,270 vs 1,650 g). Each weight group and strain was
      again represented by eight replicate groups of four birds. In Experiment 1, there
      were no strain or rearing diet effects on egg production (P > 0.05). Rearing diet
      had little long-term effect on any adult characteristics. There were significant
      (P < 0.01) strain effects on body weight, feed intake, and egg weight, although
      these were independent of rearing diet. In Experiment 2, regardless of bird
      strain, the pullets with smaller body weight matured more slowly (P < 0.01) and
      produced less total egg mass to 70 wk age (P < 0.05). These smaller birds ate
      less feed and produced smaller eggs (P < 0.01). There were strain effects,
      independent of 18-wk body weight, for egg weight and eggshell quality (P < 0.01).
      It is concluded that minor strain differences exist with respect to response to
      juvenile nutrition, although such effects are only evident in early lay. All
      strains of bird remain small, 18-wk body weight is reduced, and these birds
      subsequently eat less feed and produce smaller eggs.

PMID- 9037681
TI  - Effect of intermittent activity on broiler production parameters.
AB  - The use of intermittent lighting in broiler production has been shown to result
      in spurts of activity that appear to reduce lameness. Because intermittent
      lighting is difficult to achieve in curtain-sided houses, the objective of this
      study was to determine whether simple equipment used to increase activity in
      broilers would improve production variables. At 1 d of age, 840 male broiler
      chicks were placed in 24 floor pens. The four treatments (six replicates of 35
      chicks each) were as follows: 1) Control-standard feeders, 2) Ramps and Toys
      birds had to climb a slight incline ramp to reach feeder and had a hanging
      mobile, 3) Ramps only, and 4) Toys only-standard feeders. Two trials were
      conducted. Weekly group weights and feed consumption were recorded. Mortality was
      recorded daily. At 6 wk of age, birds were bled, euthanatized, weighted, and
      scored for ascites and tibial dyschondroplasia (TD), and relative heart, liver,
      and spleen weights were obtained. Blood samples were analyzed for blood gases,
      hemoglobin, red blood cell count, and clinical chemistries were performed. In
      Trial 1, during Weeks 2, 3, and 4, treatments with ramps had significantly
      heavier average bird weight and significantly lower feed:gain ratios. In Trial 2,
      treatments with ramps had no difference in average BW; however, these groups
      consumed less feed, resulting in significantly lower feed:gain ratios. Cumulative
      mortality was decreased by ramp treatment in Trial 2. Toys decreased the
      incidence and severity of TD in Trial 2. In general, organ weights, blood gases,
      hematologies, and clinical chemistries were not affected by treatments. However,
      birds in treatments with ramps had significantly lower serum calcium and smaller
      hearts in Trial 1, and significantly lower serum cholesterol and smaller hearts
      in Trial 2.

PMID- 9037682
TI  - Effect of lead ingestion on concentrations of lead in tissues and eggs of laying
      Tsaiya ducks in Taiwan.
AB  - This experiment was conducted to investigate Pb concentrations in soft tissues
      and eggs from laying Tsaiya ducks (Anas platyrhynchos var. domestica), dosed via
      gelatin capsule with 10 or 20 mg Pb/kg BW daily for 3 mo. Body weights of ducks
      were not influenced by Pb treatment. In addition, no clinical syndromes involving
      Pb intoxication were found throughout the experiment. The two levels of Pb
      consistently resulted in increases in the Pb content of blood, kidney, liver, and
      gizzard, whereas only 20 mg Pb/kg BW per d of dose additionally increased the Pb
      in femoral muscle. More Pb was deposited in the kidney and liver after Pb
      exposure than in the gizzard or femoral muscle. Lead residues in yolk and
      eggshell from Pb-dosed ducks were significantly higher than in controls; however,
      Pb in albumen was generally low and was not influenced by Pb treatment.

PMID- 9037683
TI  - Detecting infections of chickens with recent Salmonella pullorum isolates using
      standard serological methods.
AB  - Despite extensive testing for Salmonella pullorum infections in commercial
      poultry, occasional outbreaks of pullorum disease still occur. In some recent
      instances, questions have been raised about whether standard serological assays,
      which employ antigen strains selected several decades ago, are still able to
      detect currently prevalent S. pullorum strains. The present study evaluated the
      ability of standard rapid whole-blood plate agglutination test and serum tube
      agglutination test antigens to detect infection in Single Comb White Leghorn hens
      inoculated with large oral doses of six recent S. pullorum isolates. Two
      commercially available plate test antigens were obtained and three tube test
      antigens were prepared. All five antigens identified most inoculated hens as
      seropositive, although some differences in sensitivity were evident between the
      two assay types and between the two plate test antigens. The antigenic
      composition of the tube test antigens did not affect their ability to detect
      infections with the various inoculum strains. Regardless of the antigen used,
      hens infected with antigenically intermediate or variant S. pullorum strains were
      detected as seropositive less often than were hens infected with antigenically
      standard strains. Positive culturing results for S. pullorum in the livers and
      ovaries of infected hens were nearly always predicted by positive serological
      test results.

PMID- 9037684
TI  - The effect of added complex carbohydrates or added dietary fiber on necrotic
      enteritis lesions in broiler chickens.
AB  - Two trials utilizing two corn diets and four wheat diets were conducted. In Trial
      2, all chicks were crop-infused at 9 d of age with Eimeria acervulina. In both
      trials, a broth culture of Clostridium perfringens was mixed with the diets for 3
      consecutive d. Necrotic enteritis lesion scores were lowest in chickens consuming
      the corn diet with no C. perfringens and highest in chickens fed the wheat diets
      with C. perfringens. Chickens consuming a wheat diet with no added complex
      carbohydrates or added fiber exhibited the highest lesion score. Chickens on
      wheat diets with 4% new, ground, pine shavings had intestinal lesion scores
      intermediate to those of chickens that consumed the wheat or corn diets. Chickens
      consuming corn diets yielded the lowest lesion scores. Chickens provided diets
      containing either guar gum or pectin were not fully consumed and thus probably
      reduced the number of challenge organisms ingested.

PMID- 9037685
TI  - Effects of added dietary lard on body weight and serum glucose and low density
      lipoprotein cholesterol in randombred broiler chickens.
AB  - The effects of dietary lard on serum glucose (GLU) and lipids were determined in
      Athens-Canadian randombred broiler chickens. Birds were provided either 0, 3, or
      7% added lard in nonisocaloric starter diets through 10 d of age (S1), followed
      by either 3 or 7% added dietary lard through 21 d of age (S2). A common grower
      diet was fed to all birds after 21 d. Body and organ weights, feed conversion,
      and concentrations of various blood constituents, including serum GLU and lipids,
      were determined weekly from 14 to 42 d of age. Constant levels of added fat in
      both S1 and S2 diets generally led to higher BW in males at 42 d. Relative testes
      weight at 14 d was higher in males fed 3% than in those fed 7% S2 diets, whereas
      7% added lard in S2 diets preceded by no added fat in S1 diets resulted in higher
      relative spleen weights in males at 42 d. Serum GLU concentrations were highest
      in males that received 3% lard rather than no added lard in the S1 diet. Serum
      low density lipoprotein cholesterol (LDLC) concentrations at 14 d were highest in
      females fed constant levels of lard at either 3 or 7% in both starter periods. It
      was concluded that added lard fed to randombred chickens at various times and
      levels in starter diets elicited responses in organ weight and serum LDLC and GLU
      concentrations that varied with the sex and age of the bird and were not
      consistently related to BW.

PMID- 9037687
TI  - Evidence of increased cholecalciferol requirement in chicks with tibial
      dyschondroplasia.
AB  - A series of experiments was conducted to test the hypothesis that vitamin D
      utilization may not be as efficient in chicks with tibial dyschondroplasia (TD).
      The basal diet contained 1.0% Ca and 0.45% available P with no supplemental
      cholecalciferol (D3). Chicks from low TD (LTD) and high TD (HTD) selected lines
      were fed diets supplemented with various levels of vitamin D compounds and
      examined for rickets and TD. When chicks were fed a D3-deficient diet containing
      only 1.25 micrograms/kg added D3, HTD chicks had a greater incidence of severe
      rickets than LTD chicks (P < 0.05). The LTD chicks did not exhibit TD when fed a
      diet containing adequate (20 micrograms/kg) D3. The LTD chicks fed a diet
      supplemented with 5 micrograms/kg D3, however, had 22% incidence of TD. When HTD
      chicks were fed diets supplemented with 5 micrograms/kg D3 [control diet that
      meets NRC (1994) requirement for D3], 20 micrograms/kg D3, 5 micrograms/kg 1,25
      dihydroxycholecalciferol [1,25-(OH)2D3] or the combination of both D3 (20
      micrograms/kg) and 1,25-(OH)2D3 (5 micrograms/ kg), TD incidence was highest in
      HTD chicks fed the control diet. When HTD chicks were fed diets with an increased
      dietary level of 1,25-(OH)2D3 (10 micrograms/kg) further reduction of TD
      incidence (P < 0.05) occurred. A potentially toxic level (Soares et al., 1983) of
      1,25-(OH)2D3 (15 micrograms/kg) fed to HTD chicks resulted in still greater
      suppression of incidence of TD even though growth and feed intake in HTD chicks
      was greater than those of LTD chicks. It is concluded that the development of TD
      in HTD chicks is associated with subnormal ability to metabolize vitamin D.

PMID- 9037686
TI  - Utilization of phytate phosphorus and calcium as influenced by microbial phytase,
      cholecalciferol, and the calcium: total phosphorus ratio in broiler diets.
AB  - The present study was performed to evaluate the potential of microbial phytase
      and cholecalciferol (D3) for improving the utilization of phytate P and Ca and
      the influence of the Car:total (t) P ratio in a corn-soybean meal diet fed to
      broilers from hatch to 21 d of age. A 4 x 4 x 2 factorial arrangement of
      treatments was used: 1.1, 1.4, 1.7, and 2.0:1 Ca:tP ratio; 0, 300, 600, and 900 U
      of phytase/kg of diet; and 66 and 660 micrograms of D3/kg of diet. Another four
      treatments were included: the four Ca:tP ratios with 6,600 micrograms of D3
      addition, but without phytase. Added phytase linearly increased (P < 0.001) BW
      gain, feed intake, toe ash content, and P and Ca retention; these measurements
      were negatively influenced by widening the dietary Ca:tP ratio, and
      synergetically improved by addition of D3. Increasing the Ca:tP ratio decreased
      (P < 0.001) all measurements in the presence or absence of supplemental phytase
      and D3. Dietary Ca:tP ratios between 1.1:1 to 1.4:1 appears critical to the
      efficient use of supplemental phytase and D3 for improving the utilization of
      phytate P and Ca. The addition of D3 in corn-soybean meal diets indicated a
      potential for improving the utilization of phytate P and Ca by increasing Ca and
      P retention by about 5 to 12% in birds, which led to an increase in toe ash
      content (P < 0.03). The enhanced phytate P utilization (P < 0.001) was also
      observed during assay of the phytase activity in the mixed diets with an addition
      of D3 and without added phytase. In summary, the findings of this study suggested
      that phytase, D3, and Ca:tP are important factors in degrading phytate and
      improving phytate P and Ca utilization in broilers.

PMID- 9037688
TI  - Order of amino acid limitation in meat and bone meal.
AB  - Three experiments were conducted to determine the order of amino acid (AA)
      limitation in meat and bone meal (MBM) using AA addition and deletion assays. In
      two addition assays, various individual and combined additions of eight AA were
      made to semipurified basal diets containing 16% protein solely from a MBM. The
      two MBM had previously been determined to vary greatly in protein quality. In the
      deletion assay, a semipurified basal diet containing 13.5% CP provided solely by
      MBM was supplemented with L-Thr, L-Val, DL-Met, L-Leu, L-Ile, L-Phe, L-Tyr, L-Lys
      HCl, L-His, and L-Trp to fulfill the Illinois Ideal Protein or AA pattern on a
      digestible basis. Each AA was then deleted individually from the basal diet, and
      the effect of its deletion on growth performance was assessed. In both addition
      assays, supplementation of the MBM basal diet with Trp and Cys together yielded a
      large increase in growth performance, whereas supplementation with these AA
      individually had no effect. These results indicated that Trp and sulfur AA (with
      a primary need for Cys) were equally first limiting in the MBM. The order of
      limitation for the other AA was unclear. The results of the deletion assay showed
      that deletion of Trp, Thr, Phe + Tyr, Ile, Met, Lys, Val, or His significantly
      depressed growth performance. The results of the combined addition and deletion
      experiments indicated that the order of AA limitation in MBM was 1) Trp and
      sulfur AA, 2) Thr, 3) Ile and Phe + Tyr, 4) Met, 5) Lys, and 6) Val and His. The
      deletion assay using diets formulated on an ideal protein basis was more
      effective than the addition assay for determining the order of AA limitation in
      MBM.

PMID- 9037689
TI  - Influence of dietary levels of fat, fiber, and copper sulfate and fat rancidity
      on cecal activity in the growing turkey.
AB  - Two experiments were conducted with 6- to 10-wk-old turkeys. In Experiment 1, 6
      wk-old turkeys were fed diets varying in level of fat (4.4 to 10%) or fiber (2.5
      to 9.0%). The diets also contained extra copper as copper sulfate at either 0.1
      or 0.2% of the diet. At 8 wk of age, 15 replicate birds were housed in individual
      cages and all excreta was collected. Excreta was separated as being "regular" or
      "cecal" in origin based on appearance. At 10 wk of age, 10 birds per treatment
      were killed and cecal contents removed under anaerobic conditions. Cecal contents
      were assayed for various nutrients and viscosity was measured. In a second
      comparable study, turkeys were fed animal-vegetable fat or regular or rancid
      canola oil (60.25 vs 120.24 ng/g malonaldehyde, respectively). In Experiment 1,
      feeding copper sulfate had the most noticeable effect on various cecal
      parameters. There was an increase (P < 0.01) in dry matter cecal droppings
      produced and the cecal contents were of increased viscosity (P < 0.05). Copper
      had no effect on pH or microbial colony count of the cecal contents. Feeding
      copper resulted in a significant increase in the high molecular weight (>
      300,000) fraction of cecal contents and this fraction was of higher viscosity.
      Feeding copper sulfate resulted in a dramatic increase in copper content of cecal
      contents (280 to 11,848 ppm), although the copper content of regular excreta was
      also increased (17 to 1,008 ppm). The various levels of fiber and fat generally
      had no effect on cecal parameters. Feeding rancid canola oil did result in
      increased viscosity of cecal contents, compared to the situation seen with fresh
      canola oil. Fat rancidity per se, however, failed to influence other parameters
      such as total mass of cecal material produced and composition of cecal material.
      Feeding copper sulfate or rancid fat will increase the viscosity of cecal
      material, which may contribute to litter management problems.

PMID- 9037690
TI  - Involvement of apoptosis and lysosomal hydrolase activity in the oviducal
      regression during induced molting in chickens: a cytochemical study for end
      labeling of fragmented DNA and acid phosphatase.
AB  - Induced molting improves egg producing functions in hens. We investigated the
      mechanism of oviducal regression during induced molting. Involvement of apoptosis
      and autolysis in the oviducal regression process was analyzed by terminal
      deoxynucleotidyl transferase (T'dt)-mediated biotinylated deoxyuridine
      triphosphates (dUTP) nick end-labeling TUNEL) and an enzyme histochemistry for
      acid phosphatase. Nuclei positive for TUNEL were negligible and acid phosphatase
      staining was weak in the oviduct of laying hens. The frequency of TUNEL-positive
      nuclei was significantly increased in tubular gland cells of magnum, isthmus, and
      shell gland 2 d after cessation of egg laying and significantly decreased
      thereafter. The intensity of acid phosphatase staining was gradually increased
      during oviducal regression and extremely high on Day 7 after cessation of egg
      laying. These results suggest that during oviducal regression in induced molting
      hens, apoptosis is induced in the earlier stage of oviducal regression and
      autolysis occurs thereafter eventually, the glandular cells disappear.

PMID- 9037691
TI  - Increased fecundity resulting from semen donor selection based upon in vitro
      sperm motility.
AB  - Semen donors were selected from a population of 100 roosters based upon the
      extent to which sperm penetrated 6% (wt/vol) Accudenz from an overlay of extended
      semen. Semen donors categorized by average or high sperm motility (n = 5 per
      phenotype) were ejaculated weekly, their ejaculates pooled by phenotype, and
      pooled semen extended. A subsample of each sperm suspension was overlaid on 6%
      (wt/vol) Accudenz in a cuvette, the cuvette was placed in a 41 C water bath, and
      the absorbance of the Accudenz layer was measured after a 5-min incubation. The
      remainder of the sperm suspension was inseminated (n = 55 hens per phenotype).
      Each hen was inseminated weekly with 50 x 10(6) sperm for 14 wk. The hatchability
      of eggs laid by hens inseminated with sperm from the high motility phenotype was
      10% greater (P < or = 0.001) than that of hens inseminated with sperm from the
      average phenotype. The difference in fecundity was explicable in terms of
      fertility (P < or = 0.001). A replicate experiment tested the effect of sperm
      motility as well as insemination dose on fertility. Roosters were treated as
      above, and hens (n = 41 to 45 per phenotype) were inseminated weekly with 25, 50,
      or 100 x 10(6) sperm per hen for 3 wk. Two-way ANOVA detected a sperm motility
      effect (P < or = 0.0001) but did not detect a dose effect (P > or = 0.05) or a
      motility by dose interaction (P > or = 0.05). A posteriori comparison among means
      revealed that the maximal fertility obtained with sperm from average roosters was
      9% less (P < or = 0.05) than that obtained with only 25% as many sperm from the
      high motility phenotype. These experiments demonstrated that the fecundity of
      artificially inseminated hens can be increased when sperm penetration of Accudenz
      is used as a selection criterion for semen donors.

PMID- 9037692
TI  - Avian models in developmental biology.
AB  - The avian embryo is uniquely amenable to experimental manipulation. The most
      widely used models are chimeras resulting from heterotopic or orthotopic
      exchanges of rudiments between chick and quail embryos, according to Le Douarin's
      technique (1969). Cell migrations and fates are traced in these chimeras either
      through the identification of quail cell nuclei stained for DNA or by means of
      monoclonal antibodies that recognize a particular lineage in only one of the two
      species. The ontogeny of the hemopoietic and endothelial lineages, as enlightened
      through appropriately designed chimeras, is reviewed in the present article.
      Homologies recently disclosed in mouse and human embryo are emphasized. Finally,
      the possibilities afforded by retroviral somatic transgenesis in the avian embryo
      will be envisaged.

PMID- 9037693
TI  - Comparative development of the turkey and chicken embryo from cleavage through
      hypoblast formation.
AB  - The development of the turkey and chicken embryo from the first cleavage division
      through hypoblast formation is described. The early development of the chicken
      embryo has been categorized into 14 stages. A similar staging sequence for the
      turkey was not proposed until 1993, when we described the early development of
      the turkey embryo, which was divided into 11 stages. Comparatively, differences
      in the temporal and spatial development of the turkey and chicken blastoderm were
      evident. Of significance is the observation that at oviposition the turkey is in
      Stage VII and characterized by the first signs of area pellucida formation. In
      contrast, the chicken embryo at oviposition is in Stage X and area pellucida
      formation is completed. Similarly, the hypoblast, which is already apparent in
      the Stage X chicken embryo, does not appear in the turkey embryo until the egg is
      incubated. Furthermore, the anterior-posterior (head-tail) axis in the early
      embryo is achieved prior to oviposition in the chicken but after the onset of
      incubation in the turkey. It is apparent that the turkey embryo is less mature
      than the chicken embryo at oviposition. Whether this distinction is related to
      differences between the hatchability of turkey and chicken eggs is not yet known.

PMID- 9037694
TI  - Primordial germ cell development in avians.
AB  - The origin of the germline is studied in avians by tracing primordial germ cells
      from the stage of the germinal crescent backwards to earlier developmental
      stages. It has been demonstrated that during primitive streak formation, the
      germline has already been segregated. However, during this stage, the cells are
      seen gradually migrating from the epiblast to the hypoblast. The vertical
      migration is followed by a horizontal translocation to the extra-embryonic
      germinal crescent, being carried out by the hypoblast that is pushed anteriorly
      by the invading endodermal cells. In contrast, it has been shown that in the
      mouse the germ cells are allocated during gastrulation in a cluster of cells. Our
      results demonstrate that in avians the allocation takes place according to a
      different mode. The close association between the germ cells and the extra
      embryonic mesoderm indicates that the germline in avians, as in the mouse,
      develops from a subset of cells that have already segregated from the epiblast as
      extra-embryonic mesoderm.

PMID- 9037695
TI  - Hox genes and embryonic development.
AB  - The hox genes specify regional differences along the anterior-posterior (A/P)
      axis of the vertebrate embryo. This function appears to reflect an ancestral role
      of the hox gene complex and is conserved across phyla. During the evolution of
      vertebrates, this gene complex has been recruited to perform other functions as
      well, many of which occur later in development. Although mutational analysis in
      the mouse is well-suited to the study of their early function, that same function
      limits the utility of mutational analysis in the investigation of later
      functions. The use of retroviral vectors to alter gene expression in the chick
      embryo has emerged as an effective way to address these later functions. This
      paper reviews that approach and its application to the study of the hox genes in
      the formation of the vertebrate limb.

PMID- 9037696
TI  - The control of cell death in the early chick embryo wing bud.
AB  - Developmentally programmed cell death occurs in several regions of the chick wing
      bud. We have studied the nature and control of this cell death in vitro in
      tissues from two of these regions, the posterior necrotic zone (PNZ) and the
      opaque patch (OP). When tissue from these regions is excised prior to normal cell
      death and placed into organ culture, cell death ensues. Under these conditions,
      cell death in tissue from both of these regions is inhibited by fibroblast growth
      factor-2 (FGF-2). The only other growth factor we have found to have this
      function is insulin-like growth factor-II. Cell death in tissue from the OP and
      PNZ occurs by apoptosis, as indicated by the internucleosomal degradation of DNA
      and the inhibition of cell death by cycloheximide, an inhibitor of protein
      synthesis. If cell death is inhibited by FGF-2 and then the growth factor is
      washed away, a compensatory burst of cell death occurs in the PNZ tissue but not
      the OP tissue. This finding may indicate that in the PNZ, a death program
      progresses in the face of FGF-2 inhibition, resulting in more cells on the brink
      of death when the growth factor is removed.

PMID- 9037697
TI  - Roles for growth and differentiation factors in avian embryonic development.
AB  - We review the evidence for a role for transforming growth factor-beta (TGF-beta)
      and for tumor necrosis factor-alpha (TNF-alpha) in the development of the avian
      embryo. Transforming growth factor-beta is expressed in a number of locations in
      the early embryo with a distribution consistent with a function in epithelial
      mesenchymal transformation and modulation of the composition of the extracellular
      matrix. During gastrulation, this factor is found in the mesoderm cell layer as
      well as in the endoderm underlying the primitive streak. In vivo and in vitro
      investigations suggest that TGF-beta may be involved in the regulation of
      phenotypic transformation, matrix deposition, and cell proliferation. Tumor
      necrosis factor-alpha and its two receptors are also located with distributions
      that suggest important involvement for this pleiotropic factor in early
      morphogenetic processes. Tumor necrosis factor-alpha is found in several cell
      populations from the time of gastrulation onwards, including the lens. In vitro
      investigations, using tissue from the gastrulating embryo as well as from the
      lens, suggest that this factor may be associated with the extensive cell death
      that occurs throughout the first 6 d of development, and with nuclear
      degeneration in the lens. We hypothesize that TNF-alpha, acting in a paracrine or
      autocrine fashion, may be involved in the signalling pathways that effect the
      regulation of cell death in development.

PMID- 9037698
TI  - Regulators of adipocyte precursor cells.
AB  - Lean and adipose tissue growth are two of the most important targets for
      manipulation in commercial livestock. Adipose tissue growth occurs by both
      hyperplasia and hypertrophy. The processes involved in adipocyte hypertrophy are
      relatively well understood but much less is known about adipocyte hyperplasia.
      The mature adipocyte has little capacity for cell division and the hyperplastic
      capacity of adipose tissue resides in a population of fibroblast-like adipocyte
      precursor cells. The origin of these cells and the processes involved in their
      commitment to the adipocyte lineage is not known. Growth factors, in particular
      the bone morphogenetic proteins (BMP), are likely to be involved in regulating
      commitment to the adipocyte lineage. In vitro studies have shown that once
      committed to the adipocyte lineage, the proliferation and differentiation of,
      adipocyte precursor cells is regulated by a number of different growth factors. A
      number of these growth factors are expressed in adipocyte precursor cells in
      vitro and may have an autocrine-paracrine role. Others, such as epidermal growth
      factor (EGF), are more likely to have an endocrine role. The precise role that
      each growth factor plays in regulating adipocyte development in vivo is poorly
      understood. The chick is a useful experimental system with which to study the
      precise function of growth factors in adipocyte development.

PMID- 9037699
TI  - Modeling incubation temperature: the effects of incubator design, embryonic
      development, and egg size.
AB  - A simple model to describe the relationship between the temperature of the
      developing embryo, incubator temperature, embryo heat production, and thermal
      conductivity of the egg and surrounding air is presented. During early
      incubation, embryo temperature is slightly lower than incubator temperature
      because of evaporative cooling. However, from midincubation onwards, metabolic
      heat production from the embryo raises embryo temperature above incubator
      temperature. The extent of the rise in embryo temperature depends on thermal
      conductivity, which, in turn, is mainly influenced by the air speed over the egg.
      The importance of air speed and restrictions to air flow within artificial
      incubators is discussed. Exact determinations of optimum incubation temperatures
      from studies reported in the literature are difficult because only incubator
      temperatures are reported. Embryo temperatures can differ from incubator
      temperature because of differences in thermal conductivity between different
      incubation systems and differences between incubators in their ability to control
      temperatures uniformly. It is suggested that shell surface temperatures are
      monitored in experiments to investigate temperature effects to allow consistent
      comparisons between trials. Monitoring shell temperatures would also make it
      easier to translate optimum temperatures derived in small experimental incubators
      to the large commercial incubators used by the poultry industry. The relationship
      between egg temperature, the metabolism of the developing embryo and egg size is
      discussed.

PMID- 9037700
TI  - Effects of maternal nutrition on hatchability.
AB  - The effects of dietary factors on the development and viability of avian embryos
      have been extensively documented. A good nutritional status of the parent birds
      is crucial to the transfer to the egg of an adequate, balanced supply of
      nutrients required for normal development of the embryo. The consequences to the
      embryo may be lethal if the egg contains either inadequate, excessive, or
      imbalanced levels of nutrients. As nutritional deficiencies or excesses occur, it
      is common for the effects on the embryo to also become more severe and to occur
      at earlier stages of development. The type of nutritional stress signs visible in
      the embryo often depend upon the severity of the maternal nutritional stress.
      Diseases, parasitic infections, toxins, poisons, or drugs may also cause
      nutritional or pseudonutritional problems with hatchability.

PMID- 9037701
TI  - Egg handling and storage.
AB  - The temperature and relative humidity of storage, as well as the gaseous
      environment, interact with the fertile egg over time during storage in such a way
      as to affect the success of incubation either negatively or positively. This
      interaction occurs both above and below the "physiological zero", at which
      embryonic metabolism is minimal. This interaction below physiological zero
      implies that certain physical aspects of the egg must be affected by the
      environmental conditions. As the eggshell is a relatively fixed component,
      changes in albumen, shell membranes, cuticle, yolk, or embryo proper must account
      for these time- and environment-related effects. It is concluded that the major
      contributor is the albumen, as it is obviously the most dynamic component below
      physiological zero and is strategically positioned.

PMID- 9037702
TI  - Trace mineral metabolism in the avian embryo.
AB  - Trace mineral metabolism in the developing avian embryo begins with the formation
      of the egg and the trace mineral stores contained within it. Vitellogenin, the
      yolk precursor protein, serves as a trace mineral transporting protein that
      mediates the transfer of these essential nutrients from stores within the liver
      of the hen to the ovary and developing oocyte, and hence, to the yolk of the egg.
      Lipovitellin and phosvitin, derived from intraoocytic proteolytic processing of
      vitellogenin, are also trace mineral binding proteins that form important storage
      sites within the granule subfraction of yolk. The mobilization and uptake of egg
      trace mineral stores is mediated by the extra-embryonic membranes, principally
      the yolk sac membrane. The yolk sac also serves as a short-term storage site for
      trace minerals. Because it is an important site of plasma protein synthesis, the
      yolk sac has the ability to regulate the export of trace minerals to the embryo
      during development. Within the embryo, specific metaloproteins function in the
      interorgan transport cellular uptake, and intracellular storage of trace
      minerals. Thus, embryonic trace mineral homeostasis is established through the
      coordinated actions of the yolk sac, which mobilizes and exports trace minerals
      derived from egg stores; the vitelline circulation, which transports them to the
      embryo; and the liver, which accumulates trace minerals and distributes them to
      the rest of the tissues of the embryo via the embryonic circulation.

PMID- 9037703
TI  - Applications in in ovo technology.
AB  - By mid-August 1995, 55% of broiler embryos in North America were vaccinated for
      Marek's disease using the INOVOJECT system, with 201 INOVOJECT machines placed
      with 16 of the top 25 poultry producers, providing the industry with the capacity
      to inject in excess of 400 million eggs per month or about 5 billion eggs per
      annum. In ovo administration of a bursal disease antibody-infectious bursal
      disease virus (BDA-IBDV) complexed vaccine to specific-pathogen-free (SPF)
      embryos was safer and more potent than conventional IBDV vaccine alone because it
      delayed the appearance of bursal lesions, produced no early mortality, produced
      higher geometric mean antibody titers against IBDV, and generated protective
      immunity against challenge. In ovo administration of a BDA-IBDV complexed vaccine
      to broiler embryos generated antibody titers against IBDV sooner than
      conventional virus vaccinates, and generated protective immunity against
      challenge Direct DNA injection of plasmid DNA encoding beta-galactosidase into
      breast muscle in ovo and posthatch was an effective means to achieve both gene
      transfer and expression, with potential for the development of gene vaccines
      using plasmids encoding protective antigens from poultry pathogens. In ovo
      administration of 800 U chicken myelomonocytic growth factor (cMGF), a chicken
      hematopoietic cytokine for cells of the monocytic-granulocytic lineages,
      significantly reduced mortality associated with Escherichia coli exposure within
      the hatcher when compared to PBS controls (6.1 vs 12.4, P < or = 0.05), but not
      when compared to a yeast expression control. A procedure was developed enabling
      injection prior to the onset of incubation without compromising embryo viability.
      This in ovo injection process has opened up the window of embryo development
      during incubation for intervention, as illustrated by the 100% male phenotype
      produced in chicks hatching from eggs injected with aromatase inhibitor prior to
      incubation. These data illustrate some of the in ovo applications presently in
      use by the poultry industry, and under development or in research at EMBREX.

PMID- 9037705
TI  - Effect of calcium marination on biochemical and textural properties of peri-rigor
      chicken breast meat.
AB  - The objective of this study was to evaluate effects of marinades containing
      varying calcium concentrations on the biochemical and texture characteristics of
      peri-rigor chicken breast fillets. Breast muscles from 200 broiler chickens were
      excised immediately post-mortem and marinated in 0, 50, 100, 150, or 200 mM
      CaCl2. The treatments had no effect on meat pH either before or after cooking,
      but as calcium concentration increased, the normal post-mortem conversion of
      adenosine triphosphate (ATP) to inosine monophosphate (IMP) increased, according
      to the IMP:ATP ratios (R-values). Calcium treatment at all levels tested improved
      meat tenderness, but both marinade absorption and cooking losses increased as the
      calcium concentration in the marinades increased. It was concluded that although
      treating peri-rigor breast muscle with calcium might be useful in reducing or
      eliminating the conditioning period to assure tender chicken, methods must be
      developed for restoring the moisture binding properties that are damaged by the
      calcium.

PMID- 9037704
TI  - Principles of ex ovo competitive exclusion and in ovo administration of
      Lactobacillus reuteri.
AB  - The data that have been presented indicate that the in ovo use of competitive
      exclusion (CE) agents is feasible for both chickens and turkeys. However, there
      are many pitfalls that await the use of in ovo application of CE agents,
      including the use of nonspecies-specific intestinal microbes and the use of
      harmful proteolytic, gas-producing and toxin-producing intestinal microbes. Of
      the potential CE agents that have posthatch application, only Lactobacillus
      reuteri has been shown to be safe and effective in terms of not affecting
      hatchability and in having a prolonged effect in the hatched chick or poult.
      Lactobacillus reuteri administration in ovo increases its rate of intestinal
      colonization and decreases the colonization of Salmonella and Escherichia coli in
      both chicks and poults. Additionally, mortality due to in-hatcher exposure to E.
      coli or Salmonella is reduced with in ovo L. reuteri. Use of antibiotics in ovo
      may preclude the use of co-administered CE agents, but Gentamicin and L. reuteri
      are a compatible mixture when administered in ovo in separate compartments.
      Nevertheless, the intestinal morphology can be affected by both the CE agent and
      by antibiotics. Lactobacillus reuteri both in ovo and ex ovo will increase villus
      height and crypt depth, and Gentamicin in ovo causes a shortening and blunting of
      the villus. Both Gentamicin and L. reuteri in ovo suppress potentially pathogenic
      enteric microbes, but with diminished antibiotic effects shortening and blunting
      of the intestinal villi does not correct itself. Goblet cell numbers increase
      significantly on the ileum villus of chicks treated with Gentamicin in ovo, and
      this is presumably due to the increase in potentially pathogenic bacteria in the
      intestinal tract. Diminishing antibiotic effects posthatch would then negatively
      affect the absorption of nutrients and reduce growth at least in a transitory
      manner. Thus, L reuteri administration in ovo singly or in combination with
      Gentamicin followed by L reuteri via drinking water or feed appears to have
      potential to control many enteric pathogens in poultry. Additional work in the
      use of in ovo CE cultures is mandated because there is a world-wide movement to
      reduce antibiotic use in poultry due to increased microbial resistance to
      antibiotics. Use of naturally occurring intestinal bacterial cultures, either in
      mixed culture or as single well-defined cultures, has potential for immediate use
      in the poultry industry.

PMID- 9037706
TI  - D values of Salmonella enteritidis isolates and quality attributes of shell eggs
      and liquid whole eggs treated with irradiation.
AB  - Irradiation sensitivity of five Salmonella enteritidis isolates inoculated either
      on the surface or inside of whole shell eggs were determined. The shell eggs were
      irradiated at doses of 0, 0.5, 1.0, and 1.5 kGy. A minimal dose of 0.5 kGy was
      sufficient to eliminate all the isolates from the surface of whole eggs; however,
      the same isolates were more resistant to irradiation when present inside the
      eggs. The ATCC 13076 isolate was significantly more sensitive to irradiation,
      with a D value of 0.32 kGy, than the other four isolates from animal origin.
      Irradiation D values of the latter ranged from 0.39 to 0.41 kGy. Liquid whole
      eggs were also inoculated (2.4 x 10(6) cells per milliliter) with two S.
      enteritidis isolates and were heat-treated at 50 C for 0, 20, 40, or 60 min
      followed by irradiation at 0, 0.25, 0.5, 0.75, or 1.0 kGy. The results indicate
      that mild heating prior to irradiation was ineffective in reducing the
      irradiation D values. However, on the basis of the D values obtained, an
      irradiation dose of 1.5 kGy should be sufficient to reduce Salmonella counts by
      approximately 4 log10 in both whole shell and liquid eggs. Results also indicate
      that color and thermal characteristics of the whole or liquid eggs were
      unaffected by a 1.5-kGy dose of irradiation.

PMID- 9037707
TI  - Crystal structure of a recombinant form of the maltodextrin-binding protein
      carrying an inserted sequence of a B-cell epitope from the preS2 region of
      hepatitis B virus.
AB  - We report the crystal structure of MalE-B133, a recombinant form of the
      maltodextrin-binding protein (MBP) of Escherichia coli carrying an inserted amino
      acid sequence of a B-cell epitope from the preS2 region of the hepatitis B virus
      (HBV). The structure was determined by molecular replacement methods and refined
      to 2.7 A resolution. MalE-B133 is an insertion/deletion mutant of MBP in which
      residues from positions 134 to 142, an external alpha helix in the wild-type
      structure, are replaced by a foreign peptide segment of 19 amino acids. The
      inserted residues correspond to the preS2 sequence from positions 132 to 145 and
      five flanking residues that arise from the creation of restriction sites. The
      conformation of the recombinant protein, excluding the inserted segment, closely
      resembles that of wild-type MBP in the closed maltose-bound form. MalE-B133 was
      shown by previous studies to display certain immunogenic and antigenic properties
      of the hepatitis B surface antigen (HBsAg), which contains the preS2 region. The
      crystal structure reveals the conformation of the first nine epitope residues
      (preS2 positions 132 to 140) exposed on the surface of the molecule. The
      remaining five epitope residues (preS2 positions 141 to 145) are not visible in
      electron density maps. The path of the polypeptide chain in the visible portion
      of the insert differs from that of the deleted segment in the structure of wild
      type MBP, displaying a helical conformation at positions 134 to 140 (preS2
      sequence numbering). A tripeptide (Asp-Pro-Arg) at the N terminus of the helix
      forms a stable structural motif that may be implicated in the cross-reactivity of
      anti-HBsAg antibodies with the hybrid protein.

PMID- 9037708
TI  - Acetyl-CoA enolization in citrate synthase: a quantum mechanical/molecular
      mechanical (QM/MM) study.
AB  - Citrate synthase forms citrate by deprotonation of acetyl-CoA followed by
      nucleophilic attack of this substrate on oxaloacetate, and subsequent hydrolysis.
      The rapid reaction rate is puzzling because of the instability of the postulated
      nucleophilic intermediate, the enolate of acetyl-CoA. As alternatives, the enol
      of acetyl-CoA, or an enolic intermediate sharing a proton with His-274 in a "low
      barrier" hydrogen bond have been suggested. Similar problems of intermediate
      instability have been noted in other enzymic carbon acid deprotonation reactions.
      Quantum mechanical/molecular mechanical calculations of the pathway of acetyl-CoA
      enolization within citrate synthase support the identification of Asp-375 as the
      catalytic base. His-274, the proposed general acid, is found to be neutral. The
      acetyl-CoA enolate is more stable at the active site than the enol, and is
      stabilized by hydrogen bonds from His-274 and a water molecule. The conditions
      for formation of a low-barrier hydrogen bond do not appear to be met, and the
      calculated hydrogen bond stabilization in the reaction is less than the gas-phase
      energy, due to interactions with Asp-375 at the active site. The enolate
      character of the intermediate is apparently necessary for the condensation
      reaction to proceed efficiently.

PMID- 9037709
TI  - Conformation and stability of streptokinases from nephritogenic and
      nonnephritogenic strains of streptococci.
AB  - Conformation and stability of three Sks from Streptococcus equisimilis strain
      H46A, Streptococcus pyogenes strain A374, and Streptococcus pyogenes strain AT27
      were compared by limited proteolysis, CD, and fluorescence measurements and by
      DSC. The general similarity of the peptide CD spectra in the spectral region 185
      to 260 nm indicates the same type of folding for the three proteins. Fluorescence
      and aromatic CD spectra are consistent with a predominant surface localization of
      the aromatic amino acids and a low rigidity of their surroundings. A major
      difference among the three Sks is shown by deconvolution of their excessive heat
      capacity functions. Deconvolution reveals two energetic folding units in Sk H46A
      but three energetic folding units in Sk A374 and Sk AT27. Digestion of the Sks
      with trypsin indicates a reduced sensitivity of the C-terminal region of Sk A374
      and Sk AT27 in comparison to Sk H46A. This suggests that amino acids of the C
      terminal region participate in the formation of the third folding unit of Sk A374
      and Sk AT27.

PMID- 9037710
TI  - Improvement of protein secondary structure prediction using binary word encoding.
AB  - We propose a binary word encoding to improve the protein secondary structure
      prediction. A binary word encoding encodes a local amino acid sequence to a
      binary word, which consists of 0 or 1. We use an encoding function to map an
      amino acid to 0 or 1. Using the binary word encoding, we can statistically
      extract the multiresidue information, which depends on more than one residue. We
      combine the binary word encoding with the GOR method, its modified version, which
      shows better accuracy, and the neural network method. The binary word encoding
      improves the accuracy of GOR by 2.8%. We obtain similar improvement when we
      combine this with the modified GOR method and the neural network method. When we
      use multiple sequence alignment data, the binary word encoding similarly improves
      the accuracy. The accuracy of our best combined method is 68.2%. In this paper,
      we only show improvement of the GOR and neural network method, we cannot say that
      the encoding improves the other methods. But the improvement by the encoding
      suggests that the multiresidue interaction affects the formation of secondary
      structure. In addition, we find that the optimal encoding function obtained by
      the simulated annealing method relates to nonpolarity. This means that
      nonpolarity is important to the multiresidue interaction.

PMID- 9037711
TI  - A disulfide bridge near the active site of carbapenem-hydrolyzing class A beta
      lactamases might explain their unusual substrate profile.
AB  - Bacterial resistance to beta-lactam antibiotics, a clinically worrying and
      recurrent problem, is often due to the production of beta-lactamases, enzymes
      that efficiently hydrolyze the amide bond of the beta-lactam nucleus. Imipenem
      and other carbapenems escape the activity of most active site serine beta
      lactamases and have therefore become very popular drugs for antibacterial
      chemotherapy in the hospital environment. Their usefulness is, however,
      threatened by the appearance of new beta-lactamases that efficiently hydrolyze
      them. This study is focused on the structure and properties of two recently
      described class A carbapenemases, produced by Serratia marcescens and
      Enterobacter cloacae strains and leads to a better understanding of the
      specificity of beta-lactamases. In turn, this will contribute to the design of
      better antibacterial drugs. Three-dimensional models of the two class A
      carbapenemases were constructed by homology modeling. They suggested the
      presence, near the active site of the enzymes, of a disulfide bridge (C69-C238)
      whose existence was experimentally confirmed. Kinetic parameters were measured
      with the purified Sme-1 carbapenemase, and an attempt was made to explain its
      specific substrate profile by analyzing the structures of minimized Henri
      Michaelis complexes and comparing them to those obtained for the "classical" TEM
      1 beta-lactamase. The peculiar substrate profile of the carbapenemases appears to
      be strongly correlated with the presence of the disulfide bridge between C69 and
      C238.

PMID- 9037712
TI  - Construction and analysis of a detailed three-dimensional model of the ligand
      binding domain of the human B cell receptor CD40.
AB  - The interaction between the human B cell receptor CD40 and its ligand on T cells
      is critical for B cell proliferation and the regulation of humoral immune
      responses. CD40 is a member of the tumor necrosis factor receptor (TNFR) family.
      We report here the construction and analysis of a detailed three-dimensional
      model of the TNFR-homologous extracellular region of CD40. This study provides an
      example for structure-based model building in the presence of low sequence
      similarity. The assessment of model quality and sequence-structure compatibility
      is emphasized, and limitations of the model are discussed. The current CD40 model
      predicts structural details beyond the backbone level. Features of the CD40
      ligand binding site are discussed in conjunction with the results of a previous
      mutagenesis study.

PMID- 9037713
TI  - Perturbation of conformational dynamics, enzymatic activity, and thermostability
      of beta-glycosidase from archaeon Sulfolobus solfataricus by pH and sodium
      dodecyl sulfate detergent.
AB  - The conformational dynamics of beta-glycosidase from Sulfolobus solfataricus was
      investigated by following the emission decay arising from the large number of
      tryptophanyl residues that are homogeneously dispersed in the primary structure.
      The fluorescence emission is characterized by a bimodal lifetime distribution,
      suggesting that the enzyme structure contains rigid and flexible regions,
      properly located in the macromolecule. The enzyme activity and thermostability
      appear to be related to the dynamic properties of these regions as evidenced by
      perturbation studies of the enzyme structure at alkaline pH and by addition of
      detergents such as SDS. The pH increase affects the protein dynamics with a
      remarkable loss of thermal stability and activity; these changes occur without
      any significant variation in the secondary structure as revealed by far-UV
      dichroic measurements. In the presence of 0.02% (w/v) SDS at alkaline pH, the
      enzymatic activity and thermostability are recovered. Under these conditions, the
      conformational dynamics appear to be similar to that evidenced at neutral pH.
      Further increases in SDS concentration, at alkaline pH, render the activity and
      thermostability of beta-glycosidase similar to those observed in the absence of
      detergent.

PMID- 9037714
TI  - Ricin A-chain structural determinant for binding substrate analogues: a molecular
      dynamics simulation analysis.
AB  - Ricin A-chain is a cytotoxic protein that attacks ribosomes by hydrolyzing a
      specific adenine base from a highly conserved, single-stranded rRNA hairpin
      containing the tetraloop sequence GAGA. Molecular-dynamics simulation methods are
      used to analyze the structural determinant for three substrate analogues bound to
      the ricin A-chain molecule. Simulations were applied to the binding of the
      dinucleotide adenyl-3',5'-guanosine employing the x-ray crystal structure of the
      ricin complex and a modeled CGAGAG hexanucleotide loop taken from the NMR
      solution structure of a 29-mer oligonucleotide hairpin. A third simulation model
      is also presented describing a conformational search of the docked 29-mer
      structure by using a simulated-annealing method. Analysis of the structural
      interaction energies for each model shows the overall binding dominated by
      nonspecific interactions, which are mediated by specific arginine contracts from
      the highly basic region on the protein surface. The tetraloop conformation of the
      29-mer was found to make specific interactions with conserved protein residues,
      in a manner that favored the GAGA sequence. A comparison of the two docked loop
      conformations with the NMR structure revealed significant positional deviations,
      suggesting that ricin may use an induced fit mechanism to recognize and bind the
      rRNA substrate. The conserved Tyr-80 may play an important conformational
      entropic role in the binding and release of the target adenine in the active
      site.

PMID- 9037715
TI  - The family of the IL-6-type cytokines: specificity and promiscuity of the
      receptor complexes.
AB  - The cytokines IL-6, LIF, CNTF, OSM, IL-11, and CT-1 have been grouped into the
      family of IL-6-type cytokines, since they all require gp130 for signal
      transduction. Interestingly, gp130 binds directly to OSM, whereas complex
      formation with the other cytokines depends on additional receptor subunits. Only
      limited structural information on these cytokines and their receptors is
      available. X-ray structures have been solved for the cytokines LIF and CNTF,
      whose up-up-down-down four-helix bundle is common to all of these cytokines, and
      for the receptors of hGH and prolactin, which contain two domains with a
      fibronectin III-like fold. Since cocrystallization and x-ray analysis of the up
      to four different proteins forming the receptor complexes of the IL-6-type
      cytokines is unlikely to be achieved in the near future, model building based on
      the existing structural information is the only approach for the time being. Here
      we present model structures of the complexes of human and murine IL-6 with their
      receptors. Their validity can be deduced from the fact that published mutagenesis
      data and the different receptor specificity of human and murine IL-6 can be
      understood. It is now possible to predict the relative positions and contacts for
      all molecules in their respective complexes. Such information can be used for the
      rational design of cytokine and receptor antagonists, which may have a valuable
      therapeutic perspective.

PMID- 9037716
TI  - Large differences are observed between the crystal and solution quaternary
      structures of allosteric aspartate transcarbamylase in the R state.
AB  - Solution scattering curves evaluated from the crystal structures of the T and R
      states of the allosteric enzyme aspartate transcarbamylase from Escherichia coli
      were compared with the experimental x-ray scattering patterns. Whereas the
      scattering from the crystal structure of the T state agrees with the experiment,
      large deviations reflecting a significant difference between the quaternary
      structures in the crystal and in solution are observed for the R state. The
      experimental curve of the R state was fitted by rigid body movements of the
      subunits in the crystal R structure which displace the latter further away from
      the T structure along the reaction coordinates of the T-->R transition observed
      in the crystals. Taking the crystal R structure as a-reference, it was found that
      in solution the distance between the catalytic trimers along the threefold axis
      is 0.34 nm larger and the trimers are rotated by 11 degrees in opposite
      directions around the same axis; each of the three regulatory dimers is rotated
      by 9 degrees around the corresponding twofold axis and displaced by 0.14 nm away
      from the molecular center along this axis.

PMID- 9037717
TI  - Homology model for the human GSTT2 Theta class glutathione transferase.
AB  - A tertiary model of the human GSTT2 Theta class glutathione transferase is
      presented based on the recently solved crystal structure of a related thetalike
      isoenzyme from Lucilia cuprina. Although the N-terminal domains are quite
      homologous, the C-terminal domains share less than about 20% identity. The model
      is used to consolidate the role of Ser 11 in the active site of the enzyme as
      well as to identify other residues and mechanisms of likely catalytic importance.
      The T2 subfamily of theta class enzymes have been shown to inactivate reactive
      sulfate esters arising from arylmethanols. A possible reaction pathway involving
      the conjugation of glutathione with one such sulfate ester, 1-menaphthyl-sulfate,
      is described. It is also proposed that the C-terminal region of the enzyme plays
      an important role in allowing substrate access to the active site.

PMID- 9037718
TI  - Structural homology of spinach acyl carrier protein and Escherichia coli acyl
      carrier protein based on NMR data.
AB  - Acyl carrier proteins (ACPs) from spinach and from Escherichia coli have been
      used to demonstrate the utility of proton NMR for comparison of homologous
      structures. The structure of E. coli ACP had been previously determined and
      modeled as a rapid equilibrium among multiple conformational forms (Kim and
      Prestegard, Biochemistry 28:8792-8797, 1989). Spinach ACP showed two slowly
      exchanging forms and could be manipulated into one form for structural study.
      Here we compare this single form to postulated multiple forms of E. coli ACP
      using the limited amount of NOE data available for the spinach protein. A number
      of long-range NOE contacts were present between homologous residues in both
      spinach and E. coli ACP, suggesting tertiary structural homology. To allow a more
      definitive structural comparison, a method was developed to use spinach ACP NOE
      constraints to search for regions of structural divergence from two postulated
      forms of E. coli ACP. The homologous regions of the two protein sequences were
      aligned, additional distance constraints were extracted from the E. coli
      structure, and these were mapped onto the spinach sequence. These distance
      constraints were combined with experimental NOE constraints and a distance
      geometry simulated annealing protocol was used to test for compatibility of the
      constraints. All of the experimental spinach NOE constraints could be
      successfully combined with the E. coli data, confirming the general hypothesis of
      structural homology. A better fit was obtained with one form, suggesting a
      preferential stabilization of that form in the spinach case.

PMID- 9037719
TI  - Comparative modeling of the three-dimensional structure of the calmodulin-related
      TCH2 protein from Arabidopsis.
AB  - Plants adapt to various stresses by developmental alterations that render them
      less easily damaged. Expression of the TCH2 gene of Arabidopsis is strongly
      induced by stimuli such as touch and wind. The gene product, TCH2, belongs to the
      calmodulin (CaM) family of proteins and contains four highly conserved Ca(2+)
      binding EF-hands. We describe here the structure of TCH2 in the fully Ca(2+)
      saturated form, constructed using comparative molecular modeling, based on the x
      ray structure of paramecium CaM. Like known CaMs, the overall structure consists
      of two globular domains separated by a linker helix. However, the linker region
      has added flexibility due to the presence of 5 glycines within a span of 6
      residues. In addition, TCH2 is enriched in Lys and Arg residues relative to other
      CaMs, suggesting a preference for targets which are more negatively charged.
      Finally, a pair of Cys residues in the C-terminal domain, Cys126 and Cys131, are
      sufficiently close in space to form a disulfide bridge. These predictions serve
      to direct future biochemical and structural studies with the overall aim of
      understanding the role of TCH2 in the cellular response of Arabidopsis to
      environmental stimuli.

PMID- 9037720
TI  - Expression, purification, crystallization, and preliminary X-ray diffraction
      analysis of the homodimeric bacterial hemoglobin from Vitreoscilla stercoraria.
AB  - The recombinant homodimeric hemoglobin from the strictly aerobe gram-negative
      bacterium Vitreoscilla stercoraria has been expressed in Escherichia coli,
      purified to homogeneity, and crystallized by vapor diffusion techniques, using
      ammonium sulfate as precipitant. The crystals belong to the monoclinic space
      group P2(1) and diffract to HIGH resolution. The unit cell parameters are alpha =
      62.9, b = 42.5, c = 63.2 A, beta = 106.6 degrees; the asymmetric unit contains
      the homodimeric hemoglobin, with a volume solvent content of 42%.

PMID- 9037722
TI  - Crystallization and preliminary x-ray analysis of recombinant staphylokinase.
AB  - Diffraction quality crystals of recombinant staphylokinase (STAR) have been grown
      by the hanging drop vapor diffusion technique from a solution containing MgCl2,
      Tris buffer (pH 8.5), and polyethylene glycol 4000. The crystals belong to the
      monoclinic space group C2 with unit cell dimensions alpha = 60.6 A, b = 43.7 A, c
      = 54.3 A, and beta = 115.6 degrees. A complete native data set to 1.8 A
      resolution has been collected using synchrotron radiation.

PMID- 9037721
TI  - Crystallization and preliminary crystallographic data of a neutrophil migration
      inducing lectin (KM+) extracted from the seed of Artocarpus integrifolia.
AB  - The tetrameric KM+ lectin from the seeds of Artocarpus integrifolia has, when
      compared to other plant lectins, the singular property of directly inducing
      neutrophil migration into the peritoneal cavity or into the air pouch of rats.
      This protein crystals have been grown and they belong to the orthorhombic system
      with space group C222(1). The unit cell parameters are a = 54.4 A, b = 127.9 A
      and c = 99.8 A. A native diffraction dataset to 2.8 A was collected and an
      analysis of the self-rotation function has shown the presence of only one
      independent non-crystallographic 2-fold axis orthogonal to the crystal b-axis,
      compatible with a dimer in the asymmetric unit.

PMID- 9037731
TI  - A large duplication in the 3'-untranslated region of a subpopulation of RNA2 of
      the UK-M isolate of barley mild mosaic bymovirus.
AB  - The UK-M isolate of the bipartite barley mild mosaic bymovirus (BaMMV UK-M)
      cannot be fungally transmitted, and has previously been shown to have a 1092 nt
      deletion in the coding region of RNA2. We now report, using sequence and reverse
      transcriptase-polymerase chain reaction (RT-PCR) data, that a subpopulation of
      BaMMV UK-M RNA2 contains a direct imperfect sequence repeat of 552 nt in the 3'
      untranslated region. The secondary structure of the 3' end of RNA2, and its
      possible effects on replication of the virus, are also discussed.

PMID- 9037732
TI  - The complete nucleotide sequence of rabbit haemorrhagic disease virus (Czech
      strain V351): use of the polymerase chain reaction to detect replication in
      Australian vertebrates and analysis of viral population sequence variation.
AB  - The complete nucleotide sequence of the Czech strain of rabbit haemorrhagic
      disease virus (RHDV) was determined to be 7437 nucleotides in length with a 5
      terminal non-coding region of 9 nucleotides and a 3'-terminal non-coding region
      of 59 nucleotides. Two open reading frames (ORFs) were found within this sequence
      coding for polypeptides of 2344 (nucleotides 10-7044) and 117 amino acids
      (nucleotides 7025-7378). The sequence of this isolate was approximately 1%
      different from that reported by Meyers et al., having 78 nucleotide changes which
      resulted in 30 amino acid differences, the majority of these clustering in the N
      terminus of the large ORF and the middle of the viral coat protein. Only a single
      conservative amino acid change was seen in the smaller 3'-terminal ORF. Since the
      virus cannot at present be propagated in tissue culture, but isolated only after
      replication in rabbits, the reported sequence must be considered as a consensus
      sequence from the viral population. To gain some understanding of the possible
      sequence diversity within this virus population, 97 clones were sequenced from a
      polymerase chain reaction (PCR) fragment to determine the sequence diversity of
      the virus population. Four major classes of variant were described with mutations
      generally in the third base position of codons. A nested reverse transcriptase
      (RT) PCR (using sequence derived for the coat protein of RHDV) was used to
      determine the presence or absence of RHDV inoculated into non-host animal
      species. No replication of the virus was detected in 28 different vertebrate
      species other than rabbits. PCR tests on both mosquitoes and fleas feeding on
      RHDV infected rabbits were positive. The RT-PCR test was more sensitive when
      compared with an antigen capture ELISA to detect the presence of genomic RNA/or
      virus in infected rabbits.

PMID- 9037733
TI  - Genetic characterization of ruminant pestiviruses: sequence analysis of viral
      genotypes isolated from sheep.
AB  - Historically, the genus pestivirus was believed to contain three species of
      viruses; bovine viral diarrhea virus (BVDV), border disease virus (BDV) and
      classical swine fever virus (CSFV). However, based on limited sequence analysis
      of a small number of pestiviral isolates from domestic livestock, evidence has
      recently emerged indicating that at least four distinct genotypes exist. In an
      attempt to gain a better understanding of the degree of viral variation among
      ruminant pestiviruses, the entire structural gene coding region of an ovine
      pestivirus. BD31, genome encompassing 3358 nucleotides was cloned and sequenced.
      Sequence analysis revealed that BD31 shares less than 71% nucleotide similarity
      with other pestiviruses, suggesting, that BD31 is distinct from BVDV, CSFV as
      well as other ovine and bovine pestiviruses currently referred to as BVDV type
      II. Based on this data, BD31 is the first North American pestivirus isolate that
      falls under the category true BDV. Results from the analysis of the nucleotide
      sequence of the E0-E1 coding region of six additional ruminant pestiviruses
      identified the existence of three distinct virus genotypes in North America.
      Thus, among ruminent pestiviruses, bovine isolates can be grouped into two
      genotypes, namely types 1 and 4, whereas ovine isolates fall into genotypes 1, 3
      and 4.

PMID- 9037734
TI  - Modulation of immune cell populations and activation markers in the pathogenesis
      of African swine fever virus infection.
AB  - African swine fever (ASF) virus induces immune cell alterations that may be
      detected by changes in peripheral blood cells phenotypic antigens and activation
      markers which were examined by flow cytometry, analyzing both cell proportion
      and/or expression intensity of superficial antigens. These studies were conducted
      in pigs with experimental acute of chronic ASF infection to determine whether
      changes among important surface activation markers and phenotypic antigens, and
      their correlative lymph node status, reflected similar or disparate aspects of
      immune pathology. In acute infection produced by virulent viruses, macrophage and
      B lymphocyte populations decreased in peripheral blood after a short activation
      period at the beginning of the infection. A significative decrease of interleukin
      2 receptor (IL 2R) expression was also observed in those pigs. These variations
      correlated with lymph node cell depletion due to an intense lymphoid cell death
      by apoptosis, affecting mainly the B lymphocyte subpopulation as determined by
      immunohistochemistry. Nevertheless, pigs infected with an attenuated isolate
      undergoing chronic persistent infection, presented a distinct pattern of
      modification, according with a different clinicopathological evolution. Changes
      consisted in systemic immune activation coincident with the highest viremia
      titer, with an augmentation in CD8+ T lymphocyte, macrophage, and B cell
      populations, and MHC (major histocompatibility complex) antigens. Percentage
      elevation of circulating immune subpopulations was accompanied by cell
      accumulation with lymphoid hyperplasia but a conserved distribution of B
      lymphocytes in lymphoid organs of chronically infected pigs.

PMID- 9037735
TI  - Comparative sequence analysis and expression of the M6 gene, encoding the outer
      capsid protein VP5, of African horsesickness virus serotype nine.
AB  - The entire nucleotide and deduced amino acid sequence of the M6 gene of African
      horsesickness virus (AHSV) serotype nine has been determined from four
      overlapping cDNA clones. The gene was found to be 1566 bp long, encoding a
      protein of 505 amino acids with a molecular weight of 56 737 Da and a nett charge
      of - 1 at neutral pH Comparative sequence analysis of the deduced amino acid
      sequence with the VP5 protein of AHSV-4, showed that only 81% of amino acids were
      conserved in type and position, although alternating regions of lower and higher
      conservation was identified by alignment of the primary sequences of different
      orbiviral VP5 proteins. Antigenically authentic AHSV-9 VP5 was also expressed in
      a baculovirus expression system and the expressed protein was shown to react
      specifically with anti-AHSV-9 as well as AHSV-3 serum in Western blot analysis.

PMID- 9037736
TI  - Characterization of the 3' proximal gene of the citrus tristeza closterovirus
      genome.
AB  - The 3' proximal open reading frame (ORF 11) in the citrus tristeza virus (CTV)
      genome potentially encodes a protein of 209 amino acids with an estimated
      molecular weight of 23 kDa (p23). The p23 ORF from the severe Florida strain T36
      of CTV was expressed in Escherichia coli, and the expressed protein was used to
      raise polyclonal antibodies in a rabbit. Using these antisera on a Western blot,
      a protein of expected size (23 kDa) was detected in tissue extracts from CTV
      infected citrus but not from uninfected citrus. Most of the p23 protein was found
      in the soluble, cytoplasmic fraction. Comparison of the sequence of p23 genes
      from several biologically and geographically diverse CTV isolates indicated a
      high degree of conservation for this gene and for the RNA binding motif in
      particular. A cluster dendrogram of the deduced amino acid sequences correlated
      with the biological properties of the isolates, forming distinct groups of mild,
      quick decline on stem pitting-inducing isolates. Therefore it is possible that,
      in addition to the capsid protein gene, the p23 gene also may serve as an
      indicator for disease severity.

PMID- 9037738
TI  - Identification of mayaro virus nucleocapsid protein in nucleus of Aedes
      albopictus cells.
AB  - The modifications in the pattern of nuclear proteins of Aedes albopictus cells in
      response to Mayaro virus infection were analysed early and late after infection.
      The viral capsid (C) protein of 34 kDa (p34) could be detected in the nuclear
      compartment 4 h after infection, soon after its synthesis in the cytoplasm. In
      addition to p34, a group of high molecular weight proteins was also present in
      this compartment late after infection. The exposition of infected cells to supra
      optimal temperature of growth modifies significantly the pattern of nuclear
      proteins. However, the stress condition does not inhibit the transport of p34 to
      the nucleus. The transport of proteins into nuclei was also followed under "in
      vitro' conditions by incubating radiolabeled post-mitochondrial extract of
      infected cells with unlabeled nuclei. Under these conditions, as observed "in
      vivo', a specific transport of viral C protein and of a group of proteins of high
      molecular weight to the nuclei was also detected. These results indicate that
      Mayaro virus infection modifies the nuclear protein pattern in invertebrate
      cells.

PMID- 9037737
TI  - Identification and characterization of penton base and pVIII protein of egg drop
      syndrome virus.
AB  - The nucleotide sequence and location of the penton base and pVIII genes of the
      egg drop syndrome (EDS) virus an avian adenovirus, were determined. The penton
      base gene is located at 34.8-38.8 map units. The coding sequence has a length of
      1359 nt and encodes a polypeptide of 452 amino acids (aa) with a molecular weight
      of 51 105 Da. The amino acid sequence shows a homology of 57.3 and 55.3% to the
      structural protein IH of human adenovirus serotype 2 (HAd2) and fowl adenovirus
      serotype 1 (FAV1). The penton base protein lacks the integrin binding motifs RGD
      (Arg-Gly-Asp) and LDV (Leu-Asp-Val). At 65.1-67.3 map units an open reading frame
      of 753 nucleotides was identified which encodes the structural protein pVIH. It
      forms a protein of 250 aa with an expected molecular weight of 28 501 Da.
      Possible protease cleavage sites were identified. Amino acid homologies of 30.8
      and 27.7% were found to the HAd2 and FAV1 pVIII genes. Remarkably, the overall
      amino acid identity with ovine adenovirus pVIII is 52%. The start codons of both
      genes are shifted leftwards compared with the respective structural elements on
      the HAd2 or FAV1 genomes which indicates a different genomic organization of the
      EDS virus.

PMID- 9037739
TI  - Sequence analysis of the VP6 gene in group A turkey and chicken rotaviruses.
AB  - cDNAs corresponding to the VP6 gene of the turkey rotavirus strains Ty-1 and Ty
      3, and the chicken rotavirus strain Ch-1, were cloned and sequenced. The
      nucleotide and deduced amino acid sequence homology in the coding region of the
      VP6 gene in avian rotaviruses ranged from 78.1 to 93.9% and 86.1 to 98.7%,
      respectively. Both sequences of VP6 from avian rotaviruses exhibited a low degree
      of sequence homology (67.8-70.7% and 69.8-74.6%, respectively) compared with
      mammalian rotaviruses. Phylogenetic tree analysis showed that all avian
      rotaviruses were included in a single cluster and have separated early or from
      mammalian rotaviruses during evolution. The chicken rotavirus strain Ch-1 was a
      distant relative of other avian rotaviruses.

PMID- 9037740
TI  - Polyomavirus large T-antigen binds the "pRb related' protein p130 through
      sequences in conserved region 2.
AB  - The transforming potential of DNA tumor viruses derives mainly from the ability
      of their encoded oncogene products to interact with cellular proteins. Many of
      these viral oncoproteins share regions of sequence similarity, designated
      conserved region 1 and 2, which have been implicated in complex formation with
      pRb, the product of the retinoblastoma tumor suppressor gene, and related p107
      and p130 species. It has now been shown that the EIA protein of adenovirus is
      able to bind to all three pRb-related proteins through sequences in conserved
      region 1 and 2. We have shown previously that polyomavirus large T-antigen also
      interacts with pRb and p107 in vitro. The pRb and p107 binding domains reside
      between residues 141, 158 which include conserved region 2. In the present study,
      we demonstrate that polyomavirus large T-antigen also interacted with p130 in
      vitro through the same sequences in conserved region 2.

PMID- 9037741
TI  - Characterization of the ecdysteroid UDP-glucosyltransferase gene of a single
      nucleocapsid nucleopolyhedrovirus of Buzura suppressaria.
AB  - A putative ecdysteroid UDP-glucosyltransferase (egt) gene was identified in the
      single nucleocapsid nucleopolyhedrovirus of Buzura suppressaria (BusuNPV). This
      is the first egt gene to be characterized in a SNPV, suggesting that egt genes
      are prevalent in nucleopolyhedroviruses and possibly in all baculoviruses. The
      open reading frame (ORF) of the gene is 1539 nucleotides (nt) long, encoding a
      putative protein (EGT) of 513 amino acids (aa) with a M of 58922. The 5'
      noncoding region contains three possible TATA boxes. A polyadenylation signal,
      AATAAA, was found downstream of the translation stop codon. A putative signal
      peptide of 16 residues was present at the N-terminus of the EGT. The BusuNPV egt
      gene has a high degree of nucleotide and amino acid sequence homology to multiple
      nucleocapsid (M) NPV egt genes, the highest being to the Spodoptera exigua MNPV
      egt. A phylogenetic tree of eleven known EGTs was constructed using maximum
      parsimony analysis.

PMID- 9037742
TI  - The search for the uremic toxin: the case for metabolic acidosis.
AB  - Much effort has been expended on determining which compound, hormone or metabolic
      condition causes the uremic syndrome. Byproducts of protein metabolism that can
      cause uremic symptoms, including loss of lean body mass, have been a focus of
      research but specific toxins have been difficult to identify. Evidence is
      provided that implicates metabolic acidosis as the prime signal initiating muscle
      wasting in uremia since it activates branched-chain ketoacid dehydrogenase and
      the ubiquitin proteasome pathway. These responses degrade the essential branched
      chain amino acids and protein in muscle, leading to loss of muscle mass.
      Correction of the metabolic acidosis with sodium bicarbonate supplements has
      significant therapeutic implications for uremic patients with even mild degrees
      of metabolic acidosis.

PMID- 9037743
TI  - Antioxidant status in patients on chronic hemodialysis therapy: impact of
      parenteral selenium supplementation.
AB  - Reactive oxygen species may be involved in a broad pattern of tissue injury in
      patients on regular hemodialysis therapy and, in fact, increasing evidence
      suggests that the antioxidative system is compromized in these patients. One
      factor contributing to this reduction of antioxidative capacity is selenium
      deficiency. The present investigation was undertaken to further define the extent
      and type of impairment of the oxygen radical scavenger system in chronic
      hemodialysis patients and to evaluate the impact of selenium supplementation.
      Twelve non-wasted patients (6 male, 6 female, mean age of 58 years) on chronic
      hemodialysis for a minimum of 5 months (mean 46 months) were supplemented
      intravenously with 400 mg selenium (as sodium selenite) thrice weekly after each
      hemodialysis session over 8 weeks. Blood samples were taken before the start, at
      intervals of 2 weeks during, and 4 weeks after termination of supplementation.
      Concentrations were evaluated of selenium and alpha-tocopherol in plasma and
      erythrocytes, of retinol and ascorbic acid in plasma, of glutathione and the
      activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and,
      catalase (CAT) in erythrocytes. Lipid peroxidation endproducts were measured as
      malondialdehyde (MDA) in plasma. In patients on hemodialysis multiple alterations
      of the antioxidative system were present and the concentrations of selenium in
      plasma, of glutathione and the activity of GSH-Px in erythrocytes were profoundly
      decreased (p < 0.001). Selenium supplementation improved the selenium status of
      the patients, as indicated by an increase in selenium concentrations in plasma
      and erythrocytes and erythrocyte GSH-Px activity. Improvement in antioxidative
      capacity was further documented by an increase in alpha-tocopherol in
      erythrocytes. Plasma MDA showed a transient decrease after 6 weeks and increased
      activities of SOD and CAT were dampened. No effect was seen on plasma
      concentrations of ascorbic acid, a-tocopherol and retinol. We conclude that
      patients on chronic hemodialysis therapy manifest a profound depression in
      antioxidative potential and a selenium deficiency. Selenium supplementation
      improves the oxygen radical scavenger system and increases selenium
      concentrations in plasma and erythrocytes and the activity of selenium dependent
      glutathione peroxidase. Thus, selenium should also be considered for
      micronutrient supplementation in patients on chronic hemodialysis therapy.

PMID- 9037744
TI  - Rational use of polymerase chain reaction--based detection of viral genomes in
      patients with serologic markers of hepatitis B or C virus infection.
AB  - We studied the value of additional diagnostic information obtained by detection
      of hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA using the
      qualitative polymerase chain reaction (PCR) in patients with serologic markers of
      hepatitis B or hepatitis C virus infection. In HBV infection, all HBsAg+HBeAg+
      patients and all HBsAg+HBeAg- patients with alanine aminotransferase (ALT) levels
      > 100 U/L were positive for HBV-DNA by PCR, whereas in HBsAg+HBeAg- patients with
      ALT < 100 U/L 58% and in HBsAg+HBeAg- patients with normal aminotransferase 45%
      were found to be positive. In HBsAg+ patients no further clinically useful
      information can be obtained by PCR as the presence of HBsAg proves infection.
      However in three of 42 (7%) patients with markers of past HBV infection (antiHBs
      and/or antiHBc+) HBV-DNA was detected in the serum. Similarly, in some patients
      with acute hepatitis B HBV-DNA was demonstrable up to four months after the
      disappearance of HBsAg from serum, pointing to persistence of viremia despite the
      loss of serological markers of ongoing HBV infection. Demonstrating ongoing HBV
      infection in patients with serological markers of past infection is valuable
      additional information in only selected patients. In HCV infection, 10% of anti
      HCV+ patients with increased ALT levels had a negative serum HCV-RNA. However, in
      20% of those patients HCV-RNA was demonstrated in a serum sample collected later
      during follow-up, indicating that a single negative HCV-RNA determination cannot
      be taken as evidence for the resolution of infection.

PMID- 9037745
TI  - Orthopaedic management of juvenile chronic arthritis (JCA).
AB  - Juvenile chronic arthritis is resulting in joint destruction and frequently also
      in growth disturbances. In less than 50% pain is the cause of functional
      disability. It is important for rheumasurgeons to differentiate between the three
      main types of JCA because of the different prognosis. It is also necessary to
      realize the involvement of all connective tissue and the multiple organ
      affections in this disease, especially the kidney-function and the hematopoietic
      system. The natural course of the disease is characterized by fluctuations
      between remissions and exacerbations, more irregularly than in the adult type of
      Rh.A. The good results of rheumasurgery are highly dependent on an
      interdisciplinary combined unit, preferably working "on the same floor" in daily
      cooperation. Special training in rheumasurgical operative technique is necessary.
      Prophylactic measures against joint contractures is of great importance and
      should be common knowledge of all members of the therapeutic team. During a
      period of 13 years 528 synovectomies were performed. In a controlled study of
      open knee-synovectomies, recurrence of the inflammation was rarely seen when a
      radical early synovectomy had been performed. The centralized unit with well
      experienced staff, who master the problems of anesthesia, medication,
      intraoperative blood-transfusion and physiotherapy pre- and post-operatively, may
      obtain good results in the management of this difficult disease.

PMID- 9037746
TI  - Arthroscopic synovectomy. When, which diseases and which joints.
AB  - The success of arthroscopic synovectomy depends both on surgical skill and
      patient selection. Close cooperation between rheumatologist and rheumasurgeon is
      advocated. Alternative local joint treatments are discussed, with particular
      respect to radiation synovectomy. Patients with chronic inflammatory joint
      disease comprise the major group of patients. However, other diseases like
      haemophilia, pigmented villonodular synovitis, synovial chondromatosis,
      posttraumatic synovitis and septic arthritis are also discussed. A discussion of
      open versus arthroscopic synovectomy for each joint is presented. Arthroscopic
      synovectomy is preferred when arthroscopic access allows radical synovectomy.
      Treating concomitant tenosynovitis is underlined.

PMID- 9037747
TI  - X-ray diffraction from a helix of any length that displays cumulative azimuthal
      disorder.
AB  - An explicit formula has been derived to describe the attenuation and broadening
      of cylindrically averaged diffraction intensities from a helix of any given
      length which possesses cumulative azimuthal disorder. The application limits of
      an approximate formula, represented by the first term of this formula, are
      defined. Strategies to estimate the length of fibers, the degree of disorder, and
      the overlap of adjacent layer lines are outlined. Some features of diffraction
      patterns from the disordered helical structure of the HbS fiber are interpreted
      in light of these results. In these patterns, non-zero-order Bessel functions are
      attenuated and broadened due to azimuthal disorder and finite length. Adjacent
      layer lines overlap because of the very large axial repeat distance of the HbS
      fibers. As a result, the contribution of any Bessel function term with n > or =
      10 is not discernible in these patterns. Only Bessel terms with n < 6 may be
      accurately estimated in these patterns, if instrumental broadening is negligible
      or correctable. The theory presented here may also be used to make a rough
      estimate of the degree of disorder in F-actin fibers by comparison of X-ray
      diffraction patterns with serial peak projections calculated assuming various
      degrees of disorder.

PMID- 9037749
TI  - Anthracene-9-carboxylic acid.
AB  - Anthracene-9-carboxylic acid, C15H10O2, was found to crystallize in the
      centrosymmetric space group P2(1)/n. The hydrogen bonding is of the cyclic-dimer
      type about a center of symmetry. The carboxyl O atoms are ordered, as is the
      carboxyl H atom. The anthracene core is almost planar and shows good agreement
      with the anthracene core of anthracene-1, 8-dicarboxylic acid. The carboxyl group
      plane makes a dihedral angle of 54.87 (6) degrees with the best-fit anthracene
      core plane.

PMID- 9037748
TI  - On integrating the techniques of direct methods with anomalous dispersion. IV. A
      simplified perturbation treatment for SAS phasing.
AB  - Results from probabilistic theory for the single-wavelength anomalous-scattering
      (SAS) Friedel pair, two-phase structure invariants, psi H = phi H + phi-H, are
      used to show that the SAS three-phase structure invariants, psi HK = phi H + phi
      K + phi-H-K, tend to positive values that are easily estimated. Appropriate
      averages of the estimates provide SAS perturbation corrections in the form of
      positive origin shifts for the probability distribution of psi HK values and for
      the tangent formula. The theoretical probabilistic results are verified by
      empirical statistical analyses of model-calculated phases and experimentally
      measured structure-factor magnitudes for a small-molecule and a protein crystal
      structure.

PMID- 9037750
TI  - N-acetyl-L-glutamic acid.
AB  - In the structure of N-acetyl-L-glutamic acid, C7H11NO5, each molecule is directly
      hydrogen bonded to four others by a total of six hydrogen bonds. Two carboxylic O
      atoms and the N atom are donors, while all three acceptors are O atoms. There is
      also an intramolecular hydrogen bond with the N atom as donor and a carboxylic O
      atom as acceptor. The carboxyl O and H atoms are ordered. The conformation of the
      carbon chain with respect to the C3-C4 bond is trans as in L-glutamic acid
      hydrochloride, rather than gauche as in the beta form of L-glutamic acid.

PMID- 9037751
TI  - 5-Deoxy-5-C-(5-ethoxycarbonyl-1,2,3,- triazol-1-yl)-1,2-O-isopropylidene-alpha-D
      xylofuranose.
AB  - Two unrelated molecules of the title compound, ethyl 1-(5-deoxy-1,2-O
      isopropylidene-alpha-D-xylofuranos-5-C- yl)-1,2,3-triazole-5-carboxylate,
      C13H19N3O6, that are not linked by hydrogen bonding, comprise the asymmetric
      unit. There are no unusual bond lengths or angles. The two molecules differ in
      the degree of rotation around the methylene C atom that joins the triazole ring
      to the sugar part of the molecule. Molecules of the same conformation form
      infinite chains joined by hydrogen bonding between a H atom on the hydroxyl group
      of one molecule and an N atom in the triazole ring of another molecule generated
      by the 2(1) screw axis. Relevant intermolecular N...O distances are 3.013 (3) and
      2.806 (3) A.

PMID- 9037752
TI  - Conformational stability of LYLA1, a synthetic chimera of human lysozyme and
      bovine alpha-lactalbumin.
AB  - LYLA1 is a chimeric protein mainly consisting of residues originating from human
      lysozyme but in which the central part (Ca(2+)-binding site and helix C) of
      bovine alpha-lactalbumin has been inserted. The equilibrium unfolding of this
      hybrid protein has been examined by circular dichroism and tryptophan
      fluorescence techniques. The reversible denaturation process induced by
      temperature or by addition of chemical denaturant is three-state in the case of
      apo-LYLA1 and two-state in the presence of Ca2+. The Ca(2+)-bound form of the
      chimera exhibits higher stability than both wild-type lysozyme and alpha
      lactalbumin. The stability of the apo-form, however, is intermediate between that
      of the parent molecules. Unfolding of apo-LYLA1 involves an intermediate state
      that becomes populated to a different extent under various experimental
      conditions. Combination of circular dichroism with bis-ANS fluorescence
      experiments has permitted us to characterize the acid state of LYLA1 as a molten
      globule. Furthermore our results strongly suggest the presence of multiple
      denatured states depending on external conditions.

PMID- 9037753
TI  - A dual mechanism for impairment of GABAA receptor activity by NMDA receptor
      activation in rat cerebellum granule cells.
AB  - The function of the GABAA receptor has been studied using the whole cell voltage
      clamp recording technique in rat cerebellum granule cells in culture. Activation
      of NMDA-type glutamate receptors causes a reduction in the effect of GABA. Full
      GABAA receptor activity was recovered after washing out NMDA and NMDA action was
      prevented in a Mg+2 containing medium. The NMDA effect was also absent when
      extracellular Ca+2 was replaced by Ba+2 and when 10 mM Bapta was present in the
      intracellular solution. Charge accumulations via voltage activated Ca+2 channels
      greater than the ones via NMDA receptors do not cause any reduction in GABAA
      receptor function, suggesting that Ca+2 influx through NMDA receptor channels is
      critical for the effect. The NMDA effect was reduced by including adenosine-5'-O
      3-thiophosphate (ATP-gamma-S) in the internal solution and there was a reduction
      in the NMDA effect caused by deltamethrin, a calcineurin inhibitor. Part of the
      NMDA induced GABAA receptor impairment was prevented by prior treatment with L
      arginine. Analogously, part of the NMDA effect was prevented by blockage of NO
      synthase activity by N omega-nitro-L-arginine. A combination of NO-synthase and
      calcineurin inhibitors completely eliminated the NMDA action. An analogous result
      was obtained by combining the NO-synthase inhibitor with the addition of ATP
      gamma-S to the pipette medium. The additivity of the prevention of the NMDA
      impairment of GABAA receptor by blocking the L-arginine/NO pathway and inhibiting
      calcineurin activity suggests an independent involvement of these two pathways in
      the interaction between NMDA and the GABAA receptor. On the one hand Ca+2 influx
      across NMDA channels activates calcineurin and dephosphorylates the GABAA
      receptor complex directly or dephosphorylates proteins critical for the function
      of the receptor. On the other hand, Ca+2 influx activates NO-synthase and induces
      nitric oxide production, which regulates such receptors via protein kinase G
      activity.

PMID- 9037755
TI  - Determination of the phonon spectrum of iron in myoglobin using inelastic X-ray
      scattering of synchrotron radiation.

PMID- 9037754
TI  - Two types of modified cardiac Na+ channels after cytosolic interventions at the
      alpha-subunit capable of removing Na+ inactivation.
AB  - Failure of inactivation is the typical response of voltage-gated Na+ channels to
      the cytosolic presence of proteolytic enzymes, protein reagents such as N
      bromoacetamide (NBA) or iodate, and antibodies directed against the linker
      between domains III and IV of the alpha-subunit. The present patch clamp
      experiments with cardiac Na+ channels aimed to test the hypothesis that these
      interventions may provoke the occurrence of non-inactivating Na+ channels with
      distinct kinetic properties. A site-directed polyclonal antibody (anti-SLP2,
      target sequence 1481-1496 of the cardiac Na+ channel alpha-subunit) eliminated
      fast Na+ inactivation to induce burst activity which was accompanied by the
      occurrence of two open states. A deactivation process terminated channel activity
      during membrane depolarization proceeding with time constants of close to 40 ms
      (at -40 mV). NBA-modified and iodatemodified Na+ channels were kinetically
      indistinguishable from the anti-SLP2-modified type since they likewise deactivate
      and, thus, attain an only moderate Po of close to 20%. This is fundamentally
      different from the behaviour of enzymatically-modified Na+ channels: after
      cytosolic proteolysis with alpha-chymotrypsin, trypsin or pronase, mean Po during
      membrane depolarization amounted to approximately 40% because deactivation
      operated extremely slowly and less efficiently (time constants 100-200 ms at -40
      mV, as a minimum) or was virtually non-operating. Invitro cleavage of the
      synthetic linker sequence 1481-1496 confirmed that this part of the alpha-subunit
      provides a substrate for these peptidases or reactants for NBA but cannot be
      chemically modified by iodate. This iodate resistance indicates that iodate
      modified Na+ channels are based on a structural alteration of still another
      region which is also involved in Na+ inactivation, besides the linker between
      domains III and IV of the alpha-subunit. Endogenous peptidases such as calpain
      did not affect Na+ inactivation. This stresses the stochastic nature of a kinetic
      peculiarity of cardiac Na+ channels, mode-switching to a non-inactivating mode.

PMID- 9037756
TI  - Bacterial carnitine metabolism.
AB  - L-(-)-Carnitine is a ubiquitously occurring substance, essential for the
      transport of long-chain fatty acids through the inner mitochondrial membrane.
      Bacteria are able to metabolize this trimethylammonium compound in three
      different ways. Some, especially Pseudomonas species, assimilate L-(-)-carnitine
      as sole source of carbon and nitrogen. The first catabolic step is catalysed by
      the L-(-)-carnitine dehydrogenase. Others, for instance, Acinetobacter species,
      degrade only the carbon backbone, with formation of trimethylamine. Finally,
      various members of the Enterobacteriaceae are able to convert carnitine, via
      crotonobetaine, to gamma-butyrobetaine in the presence of C and N sources and
      under anaerobic conditions. This two-step pathway, including a L-(-)-carnitine
      dehydratase and the crotonobetaine reductase, was demonstrated in Escherichia
      coli. The DNA sequence encompassing the cai genes of E. coli, which encode the
      carnitine pathway, has been determined. Some bacteria are also able to metabolize
      the non-physiological D-(+)-carnitine, which results as a waste product in some
      chemical procedures for L-(-)-carnitine production based on the resolution of
      racemic carnitine.

PMID- 9037757
TI  - Cloning and characterization of the groE locus from Actinobacillus
      pleuropneumoniae.
AB  - A 4.4-kb DNA fragment was cloned from Actinobacillus pleuropneumoniae (strain
      4074, serotype 1) by genetic complementation with Escherichia coli groES-groEL
      mutant strains. Sequence analysis of this fragment revealed a purine nucleoside
      phosphorylase (DeoD)-encoding gene homolog (deoD), heat-shock response-encoding
      genes for the small (groES) and large subunits (groEL) and a partial open reading
      frame encoding an alcohol dehydrogenase homolog (adhE). The predicted amino-acid
      sequence of groES and groEL genes showed extensive sequence identity (80-95%)
      with other Pasteurellaceae. The gene organization surrounding the groE locus was
      different from that of Haemophilus infuenzae. When expressed in E. coli, groES
      groEL genes were capable of complementing the growth of a lambda lytic phage,
      indicating a structural as well as functional conservation.

PMID- 9037758
TI  - Inhibitory effects of nucleoside 5'-alkylphosphates on sexual agglutination in
      Saccharomyces cerevisiae.
AB  - Among various nucleoside 5'-alkylphosphates, uridine 5'-hexadecylphosphate
      (UMPC16) and adenosine 5'-hexadecylphosphate (AMPC16) inhibited the sexual
      agglutination between a and alpha haploid cells of Saccharomyces cerevisiae. The
      effect of AMPC16 accompanied severe growth inhibition of the yeast cells but it
      was not observed with UMPC16. Sexual agglutination was not inhibited by the
      presence of UMPC16 or AMPC16 when the yeast cells had been pretreated with the
      mating pheromone. UMPC16 was characterized as a specific inhibitor of sexual
      agglutination without direct influence on the agglutinin function, being
      distinguishable from any of those ever known.

PMID- 9037759
TI  - Vanadium affects vacuolation and phosphate metabolism in Hansenula polymorpha.
AB  - The yeast Hansenula polymorpha is able to grow on vanadate concentrations that
      are toxic to other organisms. Transmission electron microscopy analysis showed
      that H. polymorpha cells growing on a vanadate-containing medium undergo a
      significant increase in cell vacuolation and a thickening of the cell wall; the
      presence of small cytoplasmic vesicles and an increase in cristae at the level of
      the plasma membrane were also observed. These ultrastructural modifications were
      accompanied by a change in the intracellular polyphosphate level, as shown by in
      vivo 31P-NMR. The involvement of these observed changes in vanadium
      detoxification is discussed.

PMID- 9037760
TI  - abaB, a putative regulator for secondary metabolism in Streptomyces.
AB  - A chromosomal DNA fragment from Streptomyces antibioticus ATCC11891 was isolated
      by its ability to stimulate actinorhodin and undecylprodigiosin biosynthesis in
      Streptomyces lividans TK21. This fragment includes two open reading frames, whose
      deduced translated products resemble enzymes involved in sulfur metabolism (ORF1)
      and LysR-type transcriptional regulators (ORF2). The cloning of the promoter
      region of ORF2 (abaB) in high copy number led to overproduction of both
      antibiotics suggesting that this phenotype might well be due to titration by this
      region of one or more proteins. Southern blot analysis revealed that abaB gene is
      highly conserved among all streptomycetes tested.

PMID- 9037762
TI  - Effect of sampling procedure and strain variation in Listeria monocytogenes on
      the discrimination of species in the genus Listeria by Fourier transform infrared
      spectroscopy and canonical variates analysis.
AB  - The ability to discriminate successfully among cultures of all species of the
      Listeria genus by infrared spectroscopy in combination with canonical variate
      analysis was confirmed. The robustness of the method was demonstrated by showing
      that the separation of L. monocytogenes and L. grayi was hardly affected by
      variations in broth medium, incubation temperature, incubation time and cell
      washing procedure. Discrimination among 24 strains of L. monocytogenes according
      to serotype allowed two groups to be recognised, one comprising serotypes 4 and
      4b and the other containing serotypes 1, 1/2b and 1/2c. When strain variation was
      included in the species discrimination model, the classification of all the L.
      monocytogenes strains was virtually 100% correct.

PMID- 9037761
TI  - Comparison of the recombinant and authentic forms of the Pasteurella haemolytica
      A1 glycoprotease.
AB  - The O-sialoglycoprotein endopeptidase (glycoprotease, Gcp) is secreted by
      Pasteurella haemolytica A1, a Gram-negative pathogen associated with bovine
      pneumonic pasteurellosis. When the cloned gcp gene is expressed in Escherichia
      coli, the recombinant glycoprotease (rGcp) is exported to the periplasm but does
      not exhibit enzymatic activity. Polyclonal calf sera and murine monoclonal
      antibodies to rGcp were used for the further immunological and biochemical
      characterization of the authentic and recombinant Gcp. The results showed that
      the gcp gene product is the sole component of Gcp activity. Homologues to the P.
      haemolytica A1 Gcp were detected by Western immunoblot analysis in a number of
      Gram-negative bacteria, including E. coli. However, the secretion of Gcp with O
      sialoglycoprotein endopeptidase activity appears to be restricted to P.
      haemolytica A serotypes.

PMID- 9037763
TI  - Methanoplanus petrolearius sp. nov., a novel methanogenic bacterium from an oil
      producing well.
AB  - A disc-shaped methanogenic bacterium designated strain SEBR 4847T (T = type
      strain) was isolated from a sample collected from an African offshore oil field.
      Strain SEBR 4847T was non-motile, had a G + C content of 50 mol% and produced
      methane from H2 + CO2, formate, and CO2 + propanol. Strain SEBR 4847T grew
      optimally at 37 degrees C; no growth was observed at 25 degrees C or 45 degrees
      C. It grew in the presence of up to 50 g/l NaCl; 10-30 g/l was required for
      optimal growth. The optimum pH for growth was 7.0. Doubling time was about 10 h
      under optimal conditions. Based on 16S rRNA sequence analysis, the isolate was
      identified as a new species of the genus Methanoplanus and designated
      Methanoplanus petrolearius sp. nov. The type strain is SEBR 4847T (= OCM 486).

PMID- 9037764
TI  - Mutation in ntrC gene leading to the derepression of nitrogenase synthesis in
      Rhodobacter sphaeroides.
AB  - The Rhodobacter sphaeroides mutants Drn12 and Drn21 derepressed for nitrogenase
      synthesis in the presence of ammonia and impaired in utilization of certain
      nitrogen sources have been analyzed. Both mutants show a low level of expression
      of the glnBA operon. The DNA fragment restoring the wild-type phenotype to these
      mutants contains the 3'-portion of ntrB gene and the entire ntrC gene. Sequence
      analysis showed that Drn12 bears a missense mutation in the ntrC gene. The
      mutation results in the replacement of a glycine residue by aspartate within the
      N-terminal domain of the NtrC protein. Pleiotropic phenotypes of Drn12 and Drn21
      appear to be associated with an alteration in the regulation of glnBA expression.

PMID- 9037765
TI  - Identification and differentiation of mycobacteria using the PAN promoter
      sequence from Mycobacterium paratuberculosis as a DNA probe.
AB  - A 165 bp DNA fragment containing the PAN promoter from Mycobacterium
      paratuberculosis was used as a probe in Southern blots to detect the presence of
      related sequences in other species of mycobacteria. Among the species tested
      homologous sequences appeared to be present in representative pathogens belonging
      to the Mycobacterium tuberculosis complex, the MAIS complex, Mycobacterium
      kansasii and also the non-pathogenic vaccine strain Mycobacterium bovis BCG. In
      addition, the probe could differentiate between these species on the basis of a
      restriction fragment length polymorphism (RFLP). No hybridization was observed
      with DNA extracted from a selected group of other slow-growing and fast-growing
      mycobacteria nor from a selection of other bacterial pathogens. It appears that
      the PAN sequence is identifying genomic regions common to the major pathogenic
      groups of mycobacteria.

PMID- 9037767
TI  - The utilization of RAPD-PCR for identifying thermophilic and mesophilic Bacillus
      species.
AB  - A random amplified polymorphic DNA fingerprinting assay has been optimized that
      is able to discriminate between numerous thermophilic and mesophilic bacillus
      species and strains. Included in the analyses are thermophilic (able to grow at
      55 degrees C) strains of Bacillus stearothermophilus, B. kaustophilus, B.
      coagulans, B. sphaericus, B. thermodenitrificans, B. thermocatenulatus, B.
      thermoleovorans, B. licheniformis, B. brevis, B. thermoglucosidasius, B.
      caldolyticus, B. caldotenax, B. caldovelox, B. thermocloacae and B. smithii.
      Mesophilic strains of B. pumilus, B. subtilis, B. megaterium, B. circulans, B.
      cereus and B. mycoides can also be used for fingerprinting with the assay.
      Increasing the concentration of primer from 0.2 to 2.0 microM is shown to have a
      significant effect on increasing the number of amplification products that can be
      used for the discrimination or identification of individual strains or species.
      It is suggested that this may be a general way of improving the resolution of a
      RAPD protocol. The optimized conditions have been used successfully to trace B.
      stearothermophilus, B. licheniformis and other bacillus species and strains in an
      industrial setting.

PMID- 9037766
TI  - Characterization of group B streptococcal invasion in HEp-2 epithelial cells.
AB  - The invasion of group B streptococci (GBS) in HEp-2 epithelial cells was analyzed
      by electron microscopy and a quantitative antibiotic survival assay. Invasion of
      GBS involved intimate attachment of streptococcal chains, engulfment of the
      adherent bacteria by cellular protrusions, entry of the bacteria in a 'polar'
      fashion and formation of membrane-bound vacuoles in which most of the
      intracellular streptococci resided. At later stages of infection bacteria were
      also found free in the cytoplasm. Efficient uptake of streptococci by HEp-2 cells
      occurred within 20 min and live intracellular bacteria were detectable up to 48 h
      post-infection. Invasion of GBS required activation of the eukaryotic actin
      microfilament system involving, at least partially, protein kinase signal
      transduction pathways. Invasion was inhibited in a dose-dependent manner by
      decreasing extracellular Ca2+ levels as well as by substances known to interfere
      with eukaryotic calcium regulatory systems. These results suggest that GBS invade
      HEp-2 cells by triggering calcium-dependent phagocytosis-like internalization
      mechanisms and persist intracellularly both in vacuoles and free in the
      cytoplasm.

PMID- 9037768
TI  - Haloanaerobium congolense sp. nov., an anaerobic, moderately halophilic,
      thiosulfate- and sulfur-reducing bacterium from an African oil field.
AB  - A strictly anaerobic, moderately halophilic, Gram-negative, non-motile rod-shaped
      bacterium was isolated from an oil-well head sample of an offshore Congolese oil
      field. The strain, designated SEBR 4224T (T = type strain), grew optimally at 42
      degrees C and pH 7.0 in a complex medium containing 10% NaCl with a generation
      time of 2.5 h. Strain SEBR 4224T grew on a range of carbohydrates including
      fructose, galactose, D-glucose, maltose, D-mannose, D-ribose, sucrose, and
      trehalose. Yeast extract and/or bio-Trypcase was required for growth on
      carbohydrates and could not be replaced with amino acids and/or vitamins. The end
      products from glucose fermentation were acetate, H2, and CO2. Thiosulfate and
      elemental sulfur were used as electron acceptors. Thiosulfate improved
      carbohydrate utilization and biomass yields. The G + C content of the isolate was
      34 mol%. Ribosomal 16S rRNA sequence analysis showed that strain SEBR 4224T is a
      new member of the genus Haloanaerobium. The lack of DNA homology with H.
      acetoethylicum, its closest relative, as determined by DNA-DNA hybridization
      supports the designation of strain SEBR 4224T as a new species, Haloanaerobium
      congolense sp. nov. The type strain is SEBR 4224T (= DSM 11287).

PMID- 9037770
TI  - Abc1: a new ABC transporter from the fission yeast Schizosaccharomyces pombe.
AB  - We have isolated the abc1 gene from the fission yeast Schizosaccharomyces pombe.
      Sequence analysis suggests that the Abc1 protein is a member of the ABC
      superfamily of transporters and is composed of two structurally homologous
      halves, each consisting of a hydrophobic region of six transmembrane domains and
      a hydrophilic region containing one ATP-binding site. The abc1 gene appears to be
      expressed under all growth conditions but gene disruption experiments indicate
      that it is not essential for growth. The sequence of the abc1 gene has been
      deposited in the EMBL data library under the Accession Number Y09354.

PMID- 9037769
TI  - Comparison of the nucleotide sequence of enteroaggregative Escherichia coli heat
      stable enterotoxin 1 genes among diarrhea-associated Escherichia coli.
AB  - The presence of the enteroaggregative Escherichia coli (EAggEC) heat-stable
      enterotoxin 1 (EAST1) gene was investigated in 15 strains each of EAggEC,
      enteropathogenic E. coli (EPEC), EPEC-related strains of non-EPEC serotypes,
      diffusely adhering E. coli (type 1 DAEC) that carries F1845 adhesive pili (or a
      related adhesin), and enteroinvasive E. coli (EIEC) by PCR and colony
      hybridization. The EAST1 gene or its homologue was present in 53.3% of EAggEC,
      20% of EPEC, 13.3% of the EPEC-related strains, and 6.7% of type 1 DAEC, EIEC and
      E. coli unrelated with diarrhea had no gene with sequence similarity to the EAST1
      gene. Comparison of the EAST1 gene sequences analyzed in this study as well as
      those reported previously showed that EAggEC (including strain O42, which was
      shown to be pathogenic in volunteer experiments), EPEC, type 1 DAEC, type 2 DAEC
      (which carries the 57-kDa outer membrane protein as an adhesin), and
      enterotoxigenic E. coli shared a common sequence. A variant type of the EAST1
      gene sequence was present in the EAggEC strain 17-2 (initially characterized for
      the EAST1 gene) and in an EPEC-related strain of a non-EPEC serotype. These data
      suggest that the EAST1 gene or its variant is a virulence gene widely distributed
      among diarrhea-associated E. coli.

PMID- 9037771
TI  - Purification and characterisation of a hemolysin with phospholipase C activity
      from Vibrio cholerae O139.
AB  - A hemolysin was purified from a Vibrio cholerae O139 strain which moved as a
      single protein band of 67 kDa in SDS-PAGE. The hemolysin showed high level of
      phospholipase C activity. The purified phospholipase C-hemolysin demonstrated
      enterotoxic activity in rabbit ileal loop, suckling mice and enhanced
      permeability of rabbit skin. The pI of the purified hemolysin was 6.4.
      Erythrocytes from rabbit, chicken, guinea pig, sheep and horse were sensitive to
      the purified hemolysin in decreasing order of intensity. Erythrocytes from human
      and cow were unaffected by purified hemolysin.

PMID- 9037772
TI  - A novel bend of DNA CIT: changeable bending-center sites of an intrinsic
      curvature under temperature conditions.
AB  - We found a novel DNA curvature, which has changeable bending-center sites of an
      intrinsic curvature under temperature conditions (CIT) in the cyanobacterium
      strain Microcystis aeruginosa K-81. Circular permutation analyses (CPA) for CIT
      under different temperature conditions (4-50 degrees C) revealed that the
      changeable bending-center sites are located in the 5'-upstream region (-141 to 
      184) of the psbA2 gene, encoding the D1 protein homolog for photosynthesis. The
      nucleotide sequence around the bending center contains several dT (deoxy thymine)
      tracts, which seem to be a pivotal determinant for CIT.

PMID- 9037773
TI  - Organization of the nar genes at the chlZ locus.
AB  - The two membrane-bound respiratory nitrate reductases of Escherichia coli are
      encoded by distinct operons at two different loci, chlC and chlZ, on the
      chromosome. The chlZ locus includes a narK homologue, narU, encoding a nitrite
      extrusion protein, and narZYWV encoding nitrate reductase Z. No apparent
      homologue to the narXL operon has been found. Homology between narU and narK on
      the one hand and narZYWV and narGHJI on the other hand is limited to the coding
      regions.

PMID- 9037774
TI  - Virulence gene deletion frequency is increased in Shigella flexneri following
      conjugation, transduction, and transformation.
AB  - Some commonly used methods for introducing DNA provoke spontaneous loss of
      expression of a virulence gene located on the high molecular mass plasmid in
      Shigella flexneri. The introduction of plasmid DNA by calcium chloride-mediated
      transformation in strains harbouring wild-type or mutated copies of regulatory
      genes resulted in the loss of expression of an mxiC-lacZ reporter gene at high
      frequency, approaching 100% in some cases. Lac- segregants arose whether or not
      the introduced plasmids harboured S. flexneri virulence gene sequences.
      Conjugation and generalised transduction with bacteriophage P1 were also found to
      provoke the appearance of Lac- mutants at high frequency. The Lac- mutants
      described in this report had deletions of the regulatory genes virF or virB, or
      more extensive deletions which included structural genes. The frequency of
      mutation was greatly reduced when electroporation was used to introduce DNA into
      the strains used in this study, suggesting that this is the best method to use
      when transforming them.

PMID- 9037775
TI  - Polymerase chain reaction-single strand conformational polymorphism analysis of
      intra- and interspecific variations in organellar DNA regions of Aegilops mutica
      and related species.
AB  - In order to study the phylogeny of Aegilops mutica in the genera of Triticum and
      Aegilops, variations in chloroplast and mitochondrial DNA regions were
      investigated by polymerase chain reaction-single strand conformational
      polymorphism (PCR-SSCP) analysis. Nine lines, each of Ae. mutica and Ae.
      speltoides, were studied together with nine other Triticum and Aegilops species,
      including T. aestivum. By analyzing 9.7-kb chloroplast and 13.1-kb mitochondrial
      DNA regions, a total of 268 bands were detected, of which 176 (65.7%) showed
      variation within and/or between species. The level of intraspecific variation of
      Ae. mutica was lower than that of Ae. speltoides. The low level of the
      intraspecific variation of Ae. mutica was contrary to the expectation from
      previous studies on morphological and cytolo-gical characters. In the
      phylogenetic trees based on SSCP, Ae. mutica, Ae. speltoides and the other four
      species of the section Sitopsis (the subsection Emarginata) were separated into
      three different clusters. In addition, T. aestivum was included in the cluster of
      Ae. speltoides in the phylogenetic trees. This result suggests that Ae.
      speltoides is the cytoplasmic donor of common wheat.

PMID- 9037776
TI  - Plasmon analysis of Triticum (wheat) and Aegilops. 1. Production of alloplasmic
      common wheats and their fertilities.
AB  - Plasmons (= cytoplasms) of eight Triticum species (ten accessions) and 24
      Aegilops species (36 accessions) have been introduced by repeated backcrosses to
      12 genotypes of hexaploid, common wheat. At transfer problems such as crossing
      barrier, preferential transmission of a gametocidal or parthenogenesis-inducing
      chromosome, and mistagging of the material occurred, all of which hindered the
      plasmon transfer program. Of the 552 genotype-plasmon combinations produced, 532
      (96.4%) had reached the B10 or a later backcross generation, 15 (2.7%) the B7
      approximately B9 generation, and the remaining 5 (0.9%) the B4 approximately B6
      generation by summer, 1996. Pollen and selfed seed fertilities were observed in
      plants of all the field-grown lines in the 1992-1993 winter crop season, and
      backcrossed and selfed seed fertilities of plants grown in a greenhouse under a
      long day condition (17-h light) were assessed in the five latest backcross
      generations. Selfed seed fertility was found to be a better parameter of male
      fertility than was pollen fertility. Female fertility, as estimated from the
      backcrossed seed fertility, was about three times more tolerant to genetic stress
      caused by the alien plasmon transfer than was male fertility evaluated from both
      the pollen and selfed seed fertilities. The plasmons studied could be classified
      into 14 fertility spectrum groups. Most, excluding 15 plasmons belonging to the
      B, D, D2, S, and Sb plasmon types, were considered the male sterile plasmon to
      common wheat.

PMID- 9037777
TI  - Activation of aniline by extracts from plants and induction of chromosomal
      damages in Chinese hamster ovary cells.
AB  - Activation of aniline by plant extracts was studied by a chromosomal damage
      induction assay in Chinese hamster ovary (CHO) cells in vitro. Extracts from
      roots of Vicia faba activated aniline and the activation caused increases in
      chromosomal aberrations (CAs) and endoreduplicated cells (ERCs), but did not
      cause sister-chromatid exchanges (SCEs). Extracts from Pisum sativum and Lactuca
      sativa, however, did not activate aniline. All C-hydroxylated metabolites of
      aniline, o-aminophenol, m-aminophenol and p-aminophenol, induced not only CAs but
      also SCEs in CHO cells. These results show that the pathway for aniline
      activation by Vicia extracts is by means other than the C-hydroxylation.

PMID- 9037779
TI  - New DNA data collected and processed at DNA Data Bank of Japan.

PMID- 9037780
TI  - William Nathan Schoenfeld (1915-1996): innovative scientist, inspiring teacher,
      relentless questioner, complicated man.

PMID- 9037778
TI  - Variability of mitochondrial subgenomic molecules in the meristematic cells of
      higher plants.
AB  - MtDNAs from BY-2 cells and rice root were analyzed by random amplified
      polymorphic DNA (RAPD) assay and Southern hybridization analysis. A number of
      differences were observed in the RAPD patterns amplified from mtDNAs sampled at
      different phases of the BY-2 cell culture. RAPD fragments also varied with the
      template DNAs derived from various areas of rice root tip. When a RAPD fragment
      was hybridized to restriction fragments of whole DNAs, isolated from the distal
      area of the apical meristem and differentiated elongation zone of a root, two
      distinct stoichiometric differences were observed in the hybridization signals.
      This suggests that the organization of mt-genome in prototypic cells in the root
      apical meristem differs from that found in the differentiated cells.

PMID- 9037781
TI  - The discrimination of relative frequency by pigeons.
AB  - Five experiments addressed the issue of how pigeons learn to discriminate the
      relative frequency of stimuli. During a sampling period, three different stimuli
      (keylights) were presented serially, in mixed order, and with different
      frequencies. During a choice period, the stimuli were presented simultaneously,
      and reinforcement was arranged for choosing the stimulus that was presented the
      least number of times during the sample. The results showed that (a) the overall
      proportion of correct choices was always above chance levels; (b) the likelihood
      of a correct choice decreased with the serial position of the correct stimulus, a
      negative recency effect; (c) when the last three stimuli of the sample were
      constrained to be one of each kind, the negative recency effect decreased but
      errors became more likely when the correct stimulus occurred early in the sample,
      a negative primacy effect; (d) accurate performance generalized to new and larger
      samples; and (e) under some conditions the probability of a correct choice was
      independent of the serial position of the correct stimulus. The serial position
      curves suggest that in a least frequent discrimination task, two processes
      determine how the least frequent stimulus controls behavior: a passive decay
      process (the stimulus loses its effectiveness with time since its last
      occurrence), and a residual salience process (when the stimulus occurs in the
      first position it may decay to a higher asymptote than when it occurs in later
      positions.

PMID- 9037782
TI  - Key pecking during extinction after intermittent or continuous reinforcement as a
      function of the number of reinforcers delivered during training.
AB  - Key pecking by 7 pigeons was established and maintained on a multiple variable
      ratio variable-ratio (VR) schedule of food presentation. The schedule in one of
      the components was then changed to fixed-ratio (FR) 1 for a predetermined number
      of reinforcers. Both components were then changed to extinction (i.e., multiple
      extinction, extinction). This sequence was repeated a different number of times
      for each pigeon to determine the relation between the number of reinforcers
      delivered during each component of the multiple VR FR 1 schedule and the number
      of responses during extinction. For most pigeons, there were fewer responses
      during extinction in the presence of a stimulus recently correlated with FR 1,
      regardless of the number of reinforcers received. The ratio of the total
      responses in extinction in the former VR component to the total responses in the
      former FR 1 component increased as the number of reinforcers delivered during
      each component of the multiple schedule increased. Within-subject replications of
      the partial-reinforcement extinction effect generally occurred, and there were no
      overall reductions in the number of responses in extinction with repeated
      exposures to extinction.

PMID- 9037783
TI  - Key-peck probability and topography in a concurrent variable-interval variable
      interval schedule with food and water reinforcers.
AB  - The relation between variables that modulate the probability and the topography
      of key pecks was examined using a concurrent variable-interval variable-interval
      schedule with food and water reinforcers. Measures of response probability
      (response rates, time allocation) and topography (peck duration, gape amplitude)
      were obtained in 5 water- and food-deprived pigeons. Key color signaled
      reinforcer type. During baseline, response rates and time allocations were
      greater to the food key than to the water key, and food-key pecks had larger
      gapes and shorter durations. Relative probability measures (for the food key)
      were increased by prewatering and decreased by prefeeding. Deprivation effects
      upon topography measures were apparent only when food- and water-key pecks were
      analyzed separately. Food-key gape amplitudes increased with prewatering and
      decreased with prefeeding. The clearest effect occurred with prewatering. There
      were no consistent effects upon water-key gapes. The key color-reinforcer
      relation was reversed for 3 pigeons to determine how response topography was
      modulated during the transition from food- to water-key pecks. Reacquisition was
      faster for the probability than for the topography measures. Analysis of gape
      amplitude distributions during reversal indicated that response-form modulation
      proceeded through the generation of intermediate gape sizes.

PMID- 9037784
TI  - Body weight and response acquisition with delayed reinforcement.
AB  - The relation between body weight and responding established with unsignaled
      delayed reinforcement was investigated. In three experiments, naive rats were
      deprived to either 70%, 80%, or 90% of ad libitum weight and were then exposed to
      tandem variable-interval 15-s differential-reinforcement-of-other-behavior 30-s
      schedules. The tandem schedule defined a resetting unsignaled delay-of
      reinforcement procedure. In the first experiment, speed of magazine training,
      acquisition of lever pressing, and final rate of lever pressing were related to
      body weight. In the next experiment, lever pressing was established and
      maintained in rats that were magazine trained at 70% of ad libitum weight but
      that were then exposed to the delay procedure at 90% of ad libitum weight.
      Responding did not change consistently either across or within subjects in
      subsequent conditions in which body weight was manipulated. In the final
      experiment, lever pressing was established and maintained with delayed
      reinforcement in the absence of magazine training for each of 2 rats at 70% and
      for 1 of 2 rats at 90% of ad libitum weight. The results further illuminate the
      conditions under which responding can be established in the absence of training
      and when such responses are reinforced only following an unsignaled delay period.

PMID- 9037785
TI  - Conditioned reinforcement dynamics in three-link chained schedules.
AB  - In two experiments rats were trained on three-link concurrent-chains schedules of
      reinforcement. In Experiment 1, additional entries to one terminal link were
      added during one of the middle links to a baseline schedule that was otherwise
      equal for the two chains, and, depending on the condition, these additional
      terminal-link presentations ended either in food or in no food. When food
      occurred, preference was always in favor of the chain with the additional
      terminal-link presentations (which also entailed a higher rate of reinforcement).
      When no food occurred at the end of the additional terminal links, the outcome
      depended on the nature of the stimuli associated with these additional terminal
      links. When stimuli different from the reinforced baseline terminal links were
      used for the no-food terminal links, preference was against the choice
      alternative that led to the extra periods of extinction. When the same stimulus
      was used for the two kinds of terminal links, preference was near indifference,
      that is, significantly greater than when different stimuli were used. In
      Experiment 2, rats learned repeated reversals of a simultaneous discrimination
      under a three-link concurrent-chains schedule, in which the food or no-food
      choice outcomes were delayed until the end of the chain. Different conditions
      were defined by the point in the chain at which differential stimuli occurred.
      When the middle and terminal links provided no differential stimuli,
      discrimination was acquired more slowly than when differential stimuli occurred
      in both links. When differential stimuli occurred in the middle but not the
      terminal links, acquisition rates were intermediate. Both experiments together
      show that the effects of stimuli in a chain schedule are due partly to the time
      to food correlated with the stimuli and partly to the time to the next
      conditioned reinforcer in the sequence.

PMID- 9037786
TI  - Factors influencing survival and quality of life in burns.
AB  - Among factors influencing the improved survival of burn patients belongs
      appropriate organization of burn care with the concentration of seriously burned
      patients at specialized centers, disseminating guidelines for assessing initial
      care, triage and transfer and providing multidisciplinary treatment using newly
      developed technology. Any unprofessional and unpropitious procedure in
      resuscitation (ventilation circulation) or intensive care (surgery, nutrition,
      infection) may deteriorate the shortterm outcome. Efficacy of "accompaniment" has
      been proved in the acute period as well as during the rehabilitation and
      reconstruction period, when the scar-formation is decisive for the quality of
      life. Development and maturation of scars is influenced by individual
      differences, racial differences and psychic condition. There has to be taken into
      account the physiological status of each single patient. Among factors
      influencing long-term outcome and quality of life belong age and underlying
      diseases as well as family and society-cultural background. Patients might well
      adjust to lower levels of health by sustaining their satisfaction with life.
      Those who have recovered from critical injury may experience even an increase in
      life satisfaction, though quality of life may appear diminished.

PMID- 9037787
TI  - The influence of progress in the treatment of severe burns on the quality of
      life.
AB  - The problems related to burns treatment can be considered among the oldest and
      most passionating in history of medicine. Since the early forties amazing
      progresses have been done in the comprehension of the physiopathology of burns.
      The fast development of resuscitating techniques determined a remarkable
      reduction of mortality in the first phase; in a similar way through new concepts
      in the project and construction of intensive care facilities dedicated to burns,
      where patients can be isolated and a high standard of environmental control can
      be guaranteed, together with new topical and systemic antibacterial treatment
      protocols, a significant reduction of infectious complications has been achieved.
      Concerning surgical treatment early tangential excision and cultured epidermal
      grafts can be considered the cornerstones of burn therapy. Quality of life of
      burnt patients have been greatly ameliorated by these technical advances. Burn
      sequelae however remain the main concern of survivors because of the many
      controversial aspects of burn scar physiopathology and treatment. Along my career
      many endeavours I dedicated in this important research field. I will then report
      the results of most interesting clinical and experimental studies carried out in
      the last 30 years by our group in collaboration with basic researchers. All the
      work done in this domain enhance our hope that good results can really improve
      quality of life in burns: this is the goal for those who dedicated the whole life
      to relieve the suffering of these badly injured patients.

PMID- 9037788
TI  - Factors influencing the early prediction of outcome from burns.
AB  - OBJECTIVE: 1. To reexamine the predictive value of the variables usually used in
      admission scores in burned patients (age, total body surface area burned (TBSAB),
      full thickness burn (FTB), inhalation injury (IHT) and sex). 2. To evaluate
      whether risk factors (alcohol abuse (AA), nicotine abuse (NA)) or preexisting
      diseases influence outcome significantly. DESIGN: Retrospective study of
      prospectively collected data. PATIENTS: 498 burned patients admitted to the burn
      ICU within a 5 years period. The mean TBSAB was 29% and the mean age 38 years.
      42% of the patients suffered burns greater than 30% and the incidence of IHT
      amounted to 43%. METHODS: Univariate analyses were used to determine the
      independent relation of the variables to mortality. The relative weight of the
      variables was estimated using the step-wise logistic regression model. An
      additional analysis of subgroups was performed using classification and
      regression trees (CART). RESULTS: The univariate analyses identified the
      following variables to have significant influence on mortality: age, TBSAB, FTB,
      IHT, sex, AA, NA, the combination of AA and NA, preexisting neurological diseases
      and cardiovascular diseases. The step-wise logistic regression analysis
      identified age and TBSAB to have the most important influence on the outcome. Of
      minor weight was IHT followed by FTB and sex. The weight of IHT was found to be
      1.7 fold higher than the impact of FTB and sex. A significant influence of IHT
      was found in all patients, but especially in patients with a medium risk of death
      (20%-45%) regarding age and TBSAB. In this group AA and NA additionally caused a
      significant impact on mortality. In patients with a higher or lower probability
      of survival AA and NA did not influence the outcome. The CART analysis identified
      TBSAB to be the most discriminative variable followed by age. In the group up to
      20% TBSAB age was the only additionally significant variable regarding the
      outcome. In the group with a TBSAB between 20% and 60% age, sex and AA became
      important variables. In patients up to 72 years with a medium risk of mortality
      (20%-70%) IHT, AA, combined AA and NA, sex, preexisting neurological diseases and
      cardiovascular diseases significantly influenced outcome. In older patients IHT
      was the only additional variable of importance. CONCLUSIONS: The study
      demonstrates that besides the "classical" variables of bum scores as age, TBSAB
      and IHT other variables such as sex, AA, NA and preexisting diseases have
      significant influence on the outcome. These variables especially gain important
      predictive value in patients with a medium risk of mortality.

PMID- 9037789
TI  - Development and utilization of a psychometric instrument for measuring quality of
      life in burn patients, 1976 to 1996.
AB  - Our Burn Specific Health Scale was initially developed in 1978. Using a number of
      existing health scales, including the sickness impact profile, a depression
      scale, and the activities of daily living scale, and a large number of burn
      specific items derived from staff and patients, we eventually developed an 80
      item instrument. This instrument was divided into four domains each containing 20
      items of equal weight. The instrument was validated sequentially with intrarater,
      interrater and global validation systems, and subsequently compared with a number
      of other health and mental scales during which it performed very well. We now
      have longitudinal data which link this measurement system of quality of life to
      pre-injury educational level, to post-injury, stress disorder and predictability
      of return to work. The results indicate that total burn size has little to do
      with quality of life after recovery, and that a number of other factors play a
      bigger role, which will be presented.

PMID- 9037790
TI  - Fluid replacement in burned patients.
AB  - Burn injury involves a large amount of water, electrolytes and proteins loss
      trough the burn wound. For this reason, to avoid shock, a wide infusion of fluid
      is necessary in the first hours after trauma. Many reanimation formulas were
      proposed in the past years, with different composition: saline, colloids, plasma.
      The authors have studied 40 burned patients admitted in Verona Burn Center within
      4 hours after burn, with burns over 30% of the body surface area. Twenty of them
      were treated with Baxter reanimation formula (ringer lactated saline, RLS) while
      the others with Monafo hypertonic lactated saline (HLS), modified by Milan Burn
      Center. The two randomized groups were assessed and compared. In RLS group total
      fluid volume infused was higher while sodium requirements was lower than in HLS
      patients, with statistically significative difference (p < 0.01). On the
      contrary, in HLS group, potassium administered was perhaps twice if compared with
      the other. Haematocrit, urine output and urine osmolarity were adequate in both
      the groups, and did not showed statistical differences, such as serum proteins
      concentration, that was low in all patients, while a significative difference was
      noted in urine osmolarity (p < 0.01). A metabolic alkalosis was present in HLS
      patients, while, on the other hand, serum nitrogen was significantly higher (p <
      0.05), in the first 48 hours after burn, in RLS group. Patients were assessed for
      pre-existing diseases too, and data showed that complications were lower in HLS
      than in RLS group. HLS resuscitation formula guarantees a good electrolytes
      balance with lower fluid load, reducing tissue oedema and complication rate.
      Mortality rate was higher in HLS, may be for an higher Roy index in this group.

PMID- 9037791
TI  - Emergency treatment and early fluid resuscitation following electrical injuries.
AB  - Injuries caused by high-tension electrical current are rare, but
      pathophysiologically unique with destructive effects. As a form of thermal
      trauma, electrical injuries represent a connection of skin burns and deep tissue
      destruction unpredictable in its depth which mostly resembles a crush injury.
      Emergency treatment measures begin with the separation from the electrical
      contact if any and prompt transport to the nearest institution with all means for
      cardiorespiratory resuscitation and complete recovery. Resuscitation of the
      patient after electric shock continues then with fluid replacement using special
      formula modified for such cases, correction of acidosis and myoglobinuria and
      finally with escharotomy and fasciotomy which is most often necessary.

PMID- 9037792
TI  - Experience with the modified Meek technique.
AB  - In 1958 Meek described the so called Meek-Wall dermatome to cut postage stamp
      skin grafts. This method was eclipsed by the introduction of mesh skin grafts. In
      1993 Kreis and colleagues reintroduced a modified Meek technique using a
      dermatome running on compressed air. This technique has been used in our burn
      unit since August 1994. The aim of this paper is to compare the modified Meek
      technique with the mesh graft technique. Within a period of 20 months 41 patients
      were grafted using the modified Meek technique. The mean TBSAB was 54.4% with
      50.0% full thickness burns. All patients were excised early. The expansion ratio
      was 1:4 and 1:6. In 20 patients the Meek technique was used exclusively for
      grafting of the trunk and the extremities with the exception of face, neck and
      hands. In 3 patients with a mean TBSAB of 68.3% a combination of postage stamp
      autologous skin grafts and cultured epithelial autografts (CEA) was applied.
      Compared with the mesh graft technique the Meek technique showed the following
      advantages: 1. The Meek method provides the true expansion ratio. 2. Small graft
      remnants can be utilized. 3. Grafting of full thickness burns up to 70 to 75%
      TBSAB becomes possible with one harvest of the donor sites. 4. The reliability of
      graft take is equal or better. 5. Epithelialization is achieved within 3 to 4
      weeks depending on the expansion ratio. 6. The combination of widely expanded
      postage stamp split thickness grafts and CEA provides an excellent take rate and
      durable wound closure within a short time and avoids the problems associated with
      the engraftment of CEA on fascia. The method is simple but more demanding than
      the mesh technique. Compared with the mesh graft technique the preparation of
      Meek grafts is more time consuming and requires more staff than the Mesh
      technique. The cost of materials is higher. In our experience complete coverage
      of the Meek grafts with an overlay of meshed allografts after removal of the
      gauze as recommended by Kreis is not necessary using the 1:4 expansion ratio.
      Greater expansion ratios necessitate an overlay with meshed allografts. Regarding
      the scar formation no significant differences were observed compared with the
      mesh graft technique. In conclusion the modified Meek technique is reliable and
      simple to perform. This technique provides a sufficient expansion ratio enabling
      to graft patients with burns up to 75% TBSA with only one harvest of donor sides
      and without the necessity of CEA. In our opinion the Meek technique is reliable
      and simple to perform. This technique provides a sufficient expansion ratio
      enabling to graft patients with burns up to 75% TBSA with only one harvest of
      donor sides and without the necessity of CEA. In our opinion the Meek technique
      is advantageous in patients with burns greater than 45% TBSAB. In smaller burns
      mesh grafts should be used because of lower material cost and staff requirements.
      Especially in extensively burned patients the Meek technique may be cost
      effective avoiding the need of CEA.

PMID- 9037793
TI  - Skin expansion in burn sequelae: results and complications.
AB  - Before Radovan introduced skin expansion, burn sequelae were treated with skin
      grafts, local or distant flap, with an high morbidity on the donor site. Actually
      this technique is well known and standardized procedure that allows to obtain
      local flaps with the same characteristics in colour, texture, hair and
      sensitivity of the normal skin. The authors analyze their experience in the
      treatment of burn sequelae from 1985 to 1995. During this period, 157 patients
      underwent surgery to correct burn scars and contracture, utilizing 262 skin
      expanders. The implants were positioned on the fascial layer; antibiotic and
      drainage were routinely used. The inflation of the expander began 2 weeks after
      surgery, and hyperexpansion was the rule, when possible. Only in 6.4% (10
      patients) expansion failed, while in the remaining cases good partial (in
      patients with too large scars) or total results were achieved. Complication rate
      in skin expansion is high. In this series complication occurred in 73 of 262
      expansion, but 43 were easily solved. So only in 30 expansions the final outcome
      was influenced by complication, with higher incidence in neck and in lower
      extremities. Results were generally satisfactory, with an improvement of scars
      and minimal donor site morbidity. With a careful selection of the patients, skin
      expansion offers a good solution for burn sequelae, complications can be reduced
      and successfull results achieved.

PMID- 9037795
TI  - The use of verbal expectancy in reducing pain associated with arteriotomies.
AB  - Hospitalized patients (n = 25) receiving arteriotomies were given one of two
      verbal instructions one hour apart prior to each incision. In the first
      arteriotomy, the right radial artery was prepped with alcohol without mention and
      administered non-expectancy instruction-A, "You may or may not feel pain.
      everyone is different." One hour later, prior to the second incision, prepping
      the left radial artery with alcohol was brought to the patient's attention while
      providing expectancy instruction-B, "Notice how cool this feels, it's interesting
      how coldness numbs the skin." Analysis of variance revealed that administration
      of expectancy instruction-B significantly reduced pain (p value, < .005,
      determined by paired t-test) associated with arteriotomies.

PMID- 9037794
TI  - Applying hypnosis in a preschool family asthma education program: uses of
      storytelling, imagery, and relaxation.
AB  - A Preschool Asthma Program was conducted 4 times for children 2 to 5 years of age
      and their parent(s). Twenty-five (25) child-parent(s) participated in the 7
      session program. Data were collected prior to participation and again one year
      after completion of classes. Following participation, physician visits for asthma
      were reduced (p = 0.0013) and parents reported increased confidence in self
      management skills. Symptom severity scores improved significantly after
      participation (p < 0.001). A possible association was noted between participation
      in the program and parental expectations or projections of future outcome (0.05 <
      p < 0.1). No changes were observed in the frequency of asthma episodes or in
      pulmonary function tests before and after the program. With the hypnotherapeutic
      approach of imagery, preschoolers developed new cooperation in asthma-care
      skills, including cooperative and consistent performance of peakflow
      measurements.

PMID- 9037796
TI  - Hypnosis and cancer: an annotated bibliography 1985-1995.
AB  - The purpose of this annotated bibliography is to provide the reader with
      resources to explore the relationship between hypnosis and cancer. Items are
      included only if they contain explicit reference to this relationship and
      describe it in some detail. This bibliography includes 91 items published in
      English from 1985 to 1995, inclusive. For the reader's convenience, the
      annotations are organized into three categories: general discussions; case
      reports or case studies; and experimental and nonexperimental group designs.

PMID- 9037797
TI  - Self-hypnosis training and captivity survival.
AB  - In February and March, 1973, 566 U.S. military prisoners (POWs) were released
      from North Vietnam. These men had been POWs for a period of time between 2 months
      and 9 years, with a mean incarceration of 4.44 years. They had faced physical and
      psychological stress similar to that experienced by POWs from previous wars:
      starvation, disease, inadequate shelter, lack of medical care, interrogations and
      torture (Deaton, Burge, Richlin & Latrownik, 1977; Mitchell, 1991). By
      definition, such prison conditions constituted a traumatic experience (Deaton et
      al., 1977). However, a unique stress for our POWs in North Vietnam was the
      additional trauma of solitary confinement. This paper reviews the coping and
      "time killing" activities of U.S. Navy Vietnam POWs who experienced solitary
      confinement and tortuous interrogation. This paper also reports the physical and
      psychological adjustment of our POWs following their release from captivity.
      Suggestions are made regarding the revision of the curriculum for captivity
      survival training programs such as Survival, Evasion, Resistance, and Escape
      (SERE) school.

PMID- 9037798
TI  - Types of hypnotically (un)susceptible individuals as a function of
      phenomenological experience: towards a typology of hypnotic types.
AB  - Subjects were 194 nursing students who experienced the HGSHS A (Shor & Orne,
      1962) in which was embedded a 2-minute sitting quietly interval subsequent to the
      eye catalepsy item, but prior to the "counting out" sequence. After the HGSHS:A,
      subjects completed the Phenomenology of Consciousness Inventory (PCI) (Pekala,
      1982, 1991c) in reference to the sitting quietly interval embedded in the
      hypnotic induction ceremony. Subjects were divided into low and high susceptible
      groups. K-means cluster analysis of the subjects' responses to the PCI revealed
      nine different cluster groups. These groups had different patterns of
      phenomenological experiences that cut across individual subjects' actual HGSHS:A
      scores. Implications of the above for (a) working with clients who may not score
      that high on standard behavioral measures of hypnotizability (such as the
      HGSHS:A), or (b) understanding how hypnosis "works," are discussed.

PMID- 9037800
TI  - Mortality mapping in Hong Kong, 1979-83 and 1984-88: feasibility study and the
      patterns of cancers.
AB  - To examine the practicability and value of mapping cancers in Hong Kong, selected
      data from consecutive censuses were used to assess the demographic stability and
      socioeconomic characteristics of the 27 districts. Mortality data in two
      quinquennia (1979-1988) were used to calculate the districts' standardized
      mortality ratios (SMRs) for various cancers and their ranks were presented in
      maps. Correlations were calculated between the SMRs for the cancers, and between
      the SMRs and the socioeconomic characteristics. Population sizes and
      socioeconomic characteristics of the districts were fairly stable in most
      districts. The SMRs of many cancers differed widely between districts. Affluent
      districts tended to have high SMRs for colorectal and breast cancers, but low
      SMRs for nasopharyngeal cancer (NPC) as well as liver and lung cancers. The
      directions of the SMR ranking correlations between the two quinquennia were
      generally consistent. Statistically significant correlations between some cancers
      were replicated, particularly for males, and between some cancers and
      socioeconomic characteristics.

PMID- 9037799
TI  - A study of pattern of body mass index (BMI) and prevalence of obesity in a Saudi
      population.
AB  - The present study was conducted to assess the pattern of body mass index (BMI)
      prevalence of obesity, and the association between obesity and other health
      related problems in a Saudi population. The study was conducted in Queza district
      of Jeddah, Saudi Arabia. A systematic random sample of Saudi nationals aged 16
      years and above were selected (total number 1037; 611 males and 426 females). The
      study population was clinically examined and a specially-designed questionnaire
      was administered to obtain the information. Anthropometric measurements, blood
      pressure and urine analysis were carried out. The collected data were analyzed
      using simple as well as multivariate statistical methods. It was observed that
      BMI significantly increased with age. The crude mean BMI was significantly
      greater in females compared to males. Prevalence of Grade I obesity among
      different age groups in males ranged from 15.7% to 43.0%, while in females the
      range was from 22.8% to 45.7%. Similar patterns for both genders were found for
      Grade II obesity (5.2%-18.9%; and 11.1%-47.8% respectively). Obesity was
      significantly associated with an increase in both systolic and diastolic blood
      pressure, where increase in BMI by one unit increased systolic blood pressure by
      0.617 mm Hg, and diastolic blood pressure by 0.484 mm Hg. This relationship held
      true even after allowing for other confounding factors. The present study
      concluded that obesity is a problem prevalent in the community of Queza district.
      It is recommended that health education programs be implemented through primary
      health care services in the community to prevent this problem.

PMID- 9037801
TI  - Mortality mapping in Hong Kong, 1979-83 and 1984-88: the patterns of major non
      malignant diseases.
AB  - We examined the spatial patterns of mortality from various non-malignant diseases
      in Hong Kong during the two quinquennia, 1979-83 and 1984-88. Population data and
      parameters reflecting socioeconomic factors, including ethnic backgrounds, were
      selected from census data. Mortality data were obtained from death registration
      files. The standardized mortality ratios (SMRs) for major diseases were
      calculated for 27 census districts. The rankings of the districts' SMRs were
      shown in map form. Correlations were calculated between the districts' SMRs for
      the diseases, between them and the SMRs for cancers, and between them and
      socioeconomic and ethnic parameters. Many spatial patterns and correlations
      showed consistency and were biologically plausible. These results showed that
      mapping for a rapidly growing city such as Hong Kong could be a valuable exercise
      for detecting "at risk" populations where causal factors for non-malignant
      diseases can be investigated and identified for possible elimination.

PMID- 9037802
TI  - Assessment of malocclusion of Japanese junior high school pupils aged 12-13 years
      in Iwate prefecture according to the Dental Aesthetic Index (DAI).
AB  - The purpose of this investigation is to grasp the actual condition of
      malocclusion in Japanese junior high school pupils using the Dental Aesthetic
      Index (DAI). A total of 218 junior high school pupils aged 12-13 years were
      examined according to DAI. About 40% of the subjects had incisal crowding. The
      percentage of subjects with incisal spacing was 24%, and 71% of them had diastema
      of 1 mm or more. The percentage of subjects with anterior irregularity on the
      upper and lower arch was 39% and 33%, respectively. The percentage of subjects
      with anterior maxillary overjet and mandibular protrusion of 1 mm or more was 85%
      and 6% respectively. Dislocation by more than a half-cusp in the proximal or
      distal relationship in the molars was observed in 26% of all subjects. Mean +/-
      SD of DAI score was 25.3 +/- 7.3.

PMID- 9037803
TI  - Knowledge, attitude and practice of family planning in rural communities in
      Nigeria.
AB  - Maternal and infant mortality rates, coupled with a high population growth rate,
      are unacceptably high in Nigeria. More recently, the Nigerian government endorsed
      the promotion of reproductive health, including family planning, through maternal
      and child health services. The Ohaozara Local Government Area (LGA) introduced a
      Five-Year Action Plan (FYAP) in 1989. To appraise the Ohaozara Five-Year Action
      Plan, 600 persons stratified by geographical location and sex were interviewed in
      three randomly selected autonomous communities in the Ohaozara Local Government
      Area to determine their knowledge, attitude and practice (KAP). The findings in
      this study showed a high awareness level with a moderately positive attitude and
      generally low level of practice. Comprehensive reproductive health education
      (RHE), budgetary increase, evaluation of FYAP, and program coordination are
      recommended.

PMID- 9037804
TI  - Effects of cadmium and lead exposure on urinary N-acetyl-beta-D-glucosaminidase,
      beta 2-microglobulin and metallothionein of workers.
AB  - Cadmium (Cd), lead (Pb), N-acetyl-beta-D-glucosaminidase (NAG), beta 2
      microglobulin (BMG), metallothionein (MT) and creatinine (cre) in urine were
      measured in 36 male workers. Urinary Cd and Pb ranged from 0.2 to 9.7 and 0.1 to
      4.8 micrograms/g cre with geometric means of 1.17 and 1.27 micrograms/g cre,
      respectively. Partial correlation coefficients between the logarithm of urinary
      Cd and that of NAG, BMG or MT controlling for pH and age were 0.460 (p < 0.01),
      0.095 and 0.677 (p < 0.01), respectively. Partial correlation coefficients
      between the logarithm of Pb and that of NAG, BMG or MT controlling for pH and age
      were 0.040, 0.403 (p < 0.05) and -0.183, respectively. Multiple regression
      analysis was conducted on urinary NAG, BMG and MT using age, pH, log U-Cd and U
      Pb. Log U-Cd was the only significant predictor variable of NAG (beta = 0.572; p
      < 0.01). Log U-Pb was the only predictor variable of BMG (beta = 0.386, p <
      0.01). pH (beta = 0.286, p < 0.05) and Log U-Cd (beta = 0.839, p < 0.05) were
      significant predictor variables of MT.

PMID- 9037805
TI  - Health status, life satisfaction and health practices: a study of Pacific Asian
      and Native Hawaiian elderly cohorts.
AB  - This article describes the sociodemographic characteristics, self-ratings of
      health status, life satisfaction and health practices of Pacific Asian and Native
      Hawaiian elderly groups. The data were gathered from two separate, non-equivalent
      elderly cohorts enrolled in an elderly self-care education program in Hawaii
      during the period 1989-1992. The findings generally reflected favorable self
      ratings of health status, high life satisfaction levels, and positive health
      practices for both of these minority elderly groups. The exceptions regarding
      several health practices relate to snacking between meals, overweight problems
      and insufficient sleep for a sizable proportion of both groups. Slight to
      moderate differences between the two groups were also evident in 1) eating
      habits; 2) snacking; 3) types of physical activities; 4) weight control; 5) sleep
      patterns; 6) alcohol use; and 7) smoking. Despite the article's exploratory
      nature and limitation in the generalizability of its findings, the data offer a
      beginning database for Asian and Pacific Island elderly which is sorely lacking.

PMID- 9037806
TI  - Factors influencing smoking behavior in Hong Kong primary schoolchildren: targets
      for prevention.
AB  - The uptake of smoking by children and factors influencing such behavior, although
      well documented in the West, have not been studied in the Asia-Pacific region. A
      cross-sectional survey was carried out on 3,521 children, aged 8-11 years living
      in two districts of Hong Kong. Knowledge, attitude and behavior related to
      smoking and sociodemographic data were obtained from questionnaires completed by
      parents and children. Eleven percent of boys and 5 percent of girls were ever
      smokers, 5 percent of all eight-year-olds and 21 percent of 11-year-olds.
      Believing that parents will not interfere with their smoking (adjusted odds ratio
      5.52; 95% confidence interval 2.72, 11.18), living with family members who smoke
      (1.72; 1.33, 2.23), and having a positive attitude to smoking (4.13; 1.43, 11.98)
      were factors predictive of ever-smokers. Experimentation with smoking is a major
      health risk for primary school children in Hong Kong and indicates failure of
      current smoking prevention programs. Effective culture-specific programs to
      counteract risk factors and with continuing evaluation are urgently needed; they
      should be based on information from appropriately-designed epidemiological
      studies.

PMID- 9037807
TI  - Absenteeism in the workforce, Klang Valley, Malaysia--preliminary report.
AB  - The aim of this study was to determine the prevalence of sickness absenteeism
      among the three types of agencies, government, semi-government (boards) and
      private (public) companies. The methodology involved eliciting retrospective data
      on medical leave over the year 1990 by requesting the agencies to fill up a
      questionnaire (Appendix I), and calculating the indices of absenteeism from this
      data. The results show that the private agencies scored higher for all the
      indices but only the "lost time" percentage was significantly increased. Females
      also had significantly higher severity of sickness absenteeism rates in all the
      agencies. Overtime work was associated with higher absenteeism indices, markedly
      noted in the private agencies. In conclusion, agencies showed work out their own
      indices of absenteeism so that it could be compared with national rates.

PMID- 9037808
TI  - Battered women: presentation at A&E departments in Singapore.
AB  - This study was undertaken to assess the characteristics of battered women seen at
      the A&E department in Singapore. The first part was conducted at the A&E
      department of a general hospital in Singapore from July 4, 1992 to November 9,
      1992. Ninety-six victims were interviewed using a standard questionnaire.
      Information was obtained about the characteristics of victims, assailants and the
      assaults as well as the cause of presentation. In order to verify the
      universality of the findings, battered women seen at A&E departments of the four
      main general hospitals on the island from November 1, 1993 to January 31, 1994
      were interviewed using a similar questionnaire. We found that the majority of the
      women were beaten by someone they knew and, for most, it was not a first-time
      assault. Most times, no weapon was used. Injuries were sustained mainly to the
      face and extremities. The majority of the victims were at the A&E department
      either because of the medical examination required in conjunction with a police
      report or because of the severity of their injuries.

PMID- 9037809
TI  - Colorectal cancer risk factors: a case-control study in Bangkok.
AB  - A case-control study for colorectal cancer risk factors was conducted in Bangkok,
      Thailand. A total of 279 incident cases of colorectal cancer were individually
      matched by sex, age and same hospital to 279 hospital controls with other cancers
      except gastrointestinal cancer. Each subject was interviewed with regard to bowel
      pattern information, family history, past history of illness and dietary
      information. The major findings were elevated risk for those with a history of
      bowel polyps (OR = 14.69, 95%CI = 2.01-301.46), parent's history of colon cancer
      (OR = 4.00, 95%CI = 1.39-12.43), anal abscess (OR = 3.78, 95%CI = 0.97-17.24),
      chronic colitis (OR = 3.61, 95%CI = 1.67-8.00), chronic hemorrhoid (OR = 3.13,
      95%CI = 2.03-4.86) and the frequency of stools every three days or more (OR =
      2.16, 95%CI = 1.17-4.01). The results also indicated an increased risk for
      dietary factors; bacon (OR = 12.49, 95%CI = 1.68-269.1) and butter (OR = 2.68,
      95%CI = 1.29-5.68). There was a protective effect provided by banana (OR = 0.54,
      95%CI = 0.37-0.79) and papaya (OR = 0.58, 95%CI = 0.40-0.84) for colorectal
      cancer. In unconditional logistic regression analysis, bacon showed the highest
      risk for colorectal cancer (OR = 8.82, 95%CI = 1.03-75.57), instead of bowel
      polyps (OR = 4.50, 95%CI = 0.48-42.59). The data suggest that nitrite-treated
      meat increases colorectal cancer risk while dietary fiber decreases colorectal
      cancer risk.

PMID- 9037810
TI  - Knowledge, attitudes and perceptions related to drug abuse in peninsula Malaysia:
      a survey report.
AB  - Given the magnitude of drug addiction in Malaysia, the government has given top
      priority to this issue. It is timely that an assessment of knowledge, attitudes
      and perceptions related to drug abuse and drug dependents among the general
      public be carried out. Thus, a nationwide survey was undertaken. A representative
      sample of 2,591 respondents aged 13 years and above from households were surveyed
      throughout the 11 states and the Federal Territory of Kuala Lumpur in Peninsula
      Malaysia. The results revealed that the respondents are moderately knowledgeable
      on drug abuse, especially information pertaining to treatment, rehabilitation and
      aftercare services, including education to families against drug abuse. The
      public possess a negative attitude towards drug dependents. Majority felt that
      drug addicts do not have the will power to rid themselves of drugs and they also
      lack a supportive family network system. Many believe that the most vulnerable
      group are the adolescents. Respondents were aware of the type of drugs commonly
      abused, although they failed to realise their long-term effects. Respondents do
      not attribute low education, large family and marginal income to the background
      of drug dependents. The findings showed gaps and misconceptions in terms of
      knowledge, attitudes and perceptions of the public. Accurate knowledge on, and
      right attitudes and perceptions towards drug related issues would certainly
      benefit the public in timely prevention of drug abuse.

PMID- 9037811
TI  - Longitudinal studies of blood pressure in children.
AB  - A longitudinal study of six years was conducted to find out the pattern of
      longitudinal changes of blood pressure and to affirm the "tracking phenomenon" of
      blood pressure in children in China. We initially measured blood pressure and
      related parameters of 2,946 children (aged 4-14 years) in 1981 at Fanshan county,
      Beijing, and then two follow-up remeasurements were conducted in 1985 and 1987,
      respectively. The results indicated that: the average level of blood pressure
      increases with age even after adjusting for height and weight; tracking
      coefficients of systolic blood pressure range from weak to moderate levels,
      increasing with age. Only 30% of the children whose systolic blood pressure was
      beyond the 90th percentile of the systolic pressure distribution at the first
      examination remained at the same region after four years. Multiple stepwise
      regression was used to determine factors correlated with blood pressure. Our
      results indicate that systolic blood pressure in children is correlated with body
      weight, pulse rate, serum glucose and HDL-C, while diastolic blood pressure is
      correlated only with pulse rate and serum glucose.

PMID- 9037812
TI  - Parental smoking habits and infant birth weight.
AB  - The study was conducted from May 1991 to April 1992 to determine the factors
      which affect low infant birth weight. The sample was drawn from pregnant women
      who delivered live single infants. Weight and gender of the newborn were recorded
      as well as the parental smoking habit. The study found that there were
      significant associations between low birth weight infants and maternal smoking
      habit (RR = 2.9; p > 0.05), father's smoking habit (RR = 1.5; p > 0.05), and
      length of gestation (RR = 3.2; p > 0.05). The variables for which no association
      with low birth weight infants was observed in this study were coffee intake,
      gender of infant, and the order of birth.

PMID- 9037813
TI  - Nursing in the Pacific Basin: a crisis in health care.
AB  - Nurses in the US-Associated Pacific island jurisdictions face a number of
      problems. Data were collected in 1992 from staffing analyses, unpublished
      documents, and discussions with nurse leaders to record the status of nursing.
      The political context of nursing practice, current nursing practice, the nursing
      workforce, development of nursing resources, and the commitment of local
      governments are reviewed. Specific recommendations to address the problems are
      listed.

PMID- 9037814
TI  - Health and safety ethics for management.
AB  - All employers are ethically required to provide a safe and healthy workplace for
      their employees. Health and safety professionals (HSP) may often be employed
      either full-time or part-time to achieve this end. The HSP should be viewed as a
      non-partisan provider of safety and health services at the workplace. He is
      equally on the side of management and worker in discharging his duties. His
      primary goal is to achieve a safe and healthy workplace and to improve the health
      of the workforce. Ethical dilemmas may surface in the course of the HSP's work
      largely because there may be occasions when there are conflicts of interest and
      loyalty derived from the different roles of the HSP. The best way to resolve such
      dilemmas is to prevent them from arising. However, when this is not possible,
      management's understanding of the professional ethical considerations of the HSP
      will help to improve the working relationship and professional results of these
      staff. Several aspects in the HSP's work require management's understanding.
      These include subjects such as communicating information on staff-medical
      examinations to management, and the disclosure of commercially confidential
      information to assess related health risks. Management should also be aware that
      guidelines have been developed by a number of professional health and safety
      organizations for their members. In the instances when answers to ethical
      questions cannot be resolved, these guidelines can be consulted, in conjunction
      with discussions with senior HSP colleagues.

PMID- 9037838
TI  - Self-assessment of confidence of internee doctors in performing common surgical
      operations.
AB  - A total of 140 internee doctors who had just completed or were about to complete
      their internship training from four leading Medical College Hospitals of
      Bangladesh were asked to fill up a pre-tested structured questionnaire. Of them
      115 were male and 25 were female. All the participants had 6 months compulsory
      training in Medicine, 123 had 6 months training in Surgery and 17 had 6 months
      training in Obstetrics-Gynecology. Over 50% doctors expressed lack of confidence
      in performing ligation, vasectomy, splinting simple fractures, venesection,
      episiotomy, hydrocele operation, circumcision, proctoscopy and inguinal
      herniorrhaphy and expressed the need for further training in those procedures.
      Only 10% and 1.43% internees stated that they were confident about performing
      ligation and vasectomy independently. Internees from Chittagong Medical College
      Hospitals expressed their inability to perform ligation and/or vasectomy
      independently. So it was recommended that surgical training should be made
      mandatory for all internee Doctors with extension of the Internship period by at
      least 6 months. Emphasis should be laid on training in vasectomy and ligation. A
      pre-registration evaluation test may be introduced at the end of their training
      period.

PMID- 9037839
TI  - Hepatitis B virus markers among the prostitutes of Dhaka.
AB  - The objective of this study was to estimate the prevalence of hepatitis B virus
      (HBV) carrier states among prostitutes in Dhaka. Enzyme linked immunosorbent
      assay (ELISA) was used to detect HBV markers in a group of 164 prostitutes.
      Serological evidence of current or past HBV infection was present in 129(78.7%)
      prostitutes. HBsAg was detected in 16(9.7%) of whom 7(43.7%) were positive for e
      antigen and e-antibody was present in another 7 (43.7%). Anti-HBs was detected in
      94 (57.3%) of the specimens while anti-HBc in 108(73%) of HBsAg negative sera.
      Prevalence of HBV markers was 87% and 52.6% in VDRL reactive and non reactive
      sera respectively. The study indicates that the prevalence of HBV infection is
      high among the prostitutes in Dhaka city. Infection with Treponema pallidum is
      associated with increased risk of infection with HBV.

PMID- 9037840
TI  - Solitary thyroid nodule: a study of 100 cases.
AB  - One hundred cases of solitary thyroid nodules attending the thyroid clinic,
      Institute of Postgraduate Medicine & Research, Dhaka (IPGMR) and the Institute of
      Nuclear Medicine (INM) were included in a prospective study. Thyroid
      ultrasonography (USG), scintiscanning, radioactive iodine (I131) uptake (RAIU),
      estimation of serum total T3, T4 & TSH and Fine Needle Aspiration Cytology (FNAC)
      were performed in all cases. Surgical resection with histopathologic study was
      performed in selected cases. Extra-nodular part of the thyroid gland was normal
      in 68 and diffusely enlarged in 32, RAIU was normal in 62, high in 36 and very
      low in two subjects. Nodules were solid at USG in 67 subjects, cystic in 16
      subjects and of mixed consistency in 17 subjects. Goitrous subjects had
      significantly lower T4 (p < 0.001) and higher T3 (p < 0.01) and TSH (p < 0.001)
      than non-goitrous ones. Colloid nodule was the commonest pathology occurring in
      41 cases, followed by thyroid cysts (26), follicular adenoma (23), adenoma with
      cystic change (7), subacute thyroiditis (2) and papillary carcinoma (1). Colloid
      nodules were more common in goitrous subjects which could hint at iodine
      deficiency as the major cause of such nodules. Hyperfunctioning follicular
      adenomas occurred exclusively in non-goitrous subjects. Carcinoma appeared to be
      uncommon in patients with solitary nodules. It gives an opportunity to our
      physicians to be more conservative in selecting patients with solitary thyroid
      nodules for surgical treatment.

PMID- 9037841
TI  - Ruptured aneurysm of the sinus of Valsalva.
AB  - The objective of the present study was to assess the value of imaging techniques
      in the diagnosis of ruptured aneurysm of sinus of Valsalva (RASV). 38 patients
      were included in the study. 30 were male and 8 female. Their age ranged from 7 to
      55 years (mean 25.8 years). Echocardiographic and doppler studies were done in
      all cases and 20 patients underwent catheterization and angiography. Two patients
      were asymptomatic, 20 (53%) had acute onset of symptoms and in the remaining 16
      (42%) patients symptoms developed gradually. Twenty two (58%) patients were in
      NYHA functional class III or IV when first seen. Predominant symptoms were
      dyspnea (79%), palpitation (55%) and chest pain (52%). A continuous machinery
      murmur was detected in all the patients with associated thrill in 34 patients.
      Right coronary sinus (RCS) was the most common sinus involved (89%) followed by
      the noncoronary sinus (NCS) which was involved in 11% of patients. None of the
      patients in our series had aneurysm of the left coronary sinus. Twenty eight of
      the 34 RCS aneurysms ruptured into the right ventricular outflow tract (RVOT), 4
      into right ventricular cavity (RVC), one into right atrium (RA) and one dissected
      into the ventricular septum and subsequently ruptured into the left ventricle. Of
      the 4 NCS aneurysms, 2 ruptured into RVC, one into RA and one into both the RA
      and RVC. Associated ventricular septal defect (VSD) was found in 10 (26%)
      patients and all of these patients had RCS aneurysm that ruptured into the RVOT.
      Aortic regurgitation (AR) was detected in 16 (42%) cases. Discrete subaortic
      stenosis was detected in one patient who also had associated VSD and AR.
      Vegetation of the aortic valve was detected in one patient who had RCS aneurysm.
      Twelve patients (11 male and one female) underwent surgical correction, 10 with
      and 2 without prior catheterization. Localization of the involved sinus, site of
      rupture and associated cardiac lesions by echocardiography and doppler study were
      found accurate at surgery and/or angiography in 22 cases of our series. Imaging
      techniques, thus appeared to be reliable tools for the diagnosis of RASV.

PMID- 9037842
TI  - Comparative studies on IFAT, ELISA & DAT for serodiagnosis of visceral
      leishmaniasis in Bangladesh.
AB  - The purpose of the study was to estimate the specificity and sensitivity of
      different serological methods for the diagnosis of visceral leishmaniasis in
      Bangladesh. Blood samples from 155 suspected kala-azar patients together with 80
      sick subjects and 50 healthy subjects from the endemic areas were collected. Out
      of the 155 suspected kala-azar patients, bone marrow were collected from 126
      patients. All bone marrow samples were examined by direct microscopy. 92 bone
      marrow samples were also examined by culture method. Blood samples were examined
      by various serological tests. Out of 126 marrow samples, LD bodies were present
      by microscopy in 77 (61.1%) cases and out of 92 marrow samples, cultures for LD
      bodies were positive in 33 (35.9%) cases. All the three serological tests (IFAT,
      ELISA & DAT) were positive in all parasitologically positive kala-azar patients.
      They were also positive in seven (15.5%) out of 45 parasitologically negative
      cases and 10 (34.4%) out of remaining 29 cases in whom bone marrow samples were
      not available. Thus the serological tests proved to be simple, non-invasive,
      highly sensitive and specific methods for the diagnosis of visceral
      leishmaniasis. DAT is the simplest of these serological tests, although these
      tests did not differ in sensitivity and specificity.

PMID- 9037843
TI  - A study of prolonged pyrexia in Dhaka.
AB  - In a prospective study conducted in the Institute of Postgraduate Medicine &
      Research (IPGMR), Dhaka, 212 patients with prolonged pyrexia were thoroughly
      evaluated clinically and with the help of laboratory investigations with a view
      to reaching the diagnosis. Their clinical and laboratory data were recorded.
      Clinical features pertaining to a particular organ gave appropriate clue in 52%
      cases. Imaging techniques were instrumental in 24%, microbiological or
      serological investigations in 35%, invasive procedures were diagnostic in 42%,
      laparotomy had to be resorted to in five cases. Infectious diseases were the
      commonest causes of prolonged pyrexia accounting for about 63.21% of cases
      followed by neoplasms (12.74%) and connective tissue disorders (10.85%).
      Tuberculosis was the most common infection (24.53% of all cases) followed by
      enteric fever (12.74%) and visceral leishmaniasis (9.43%). Pleura was the
      commonest seat for tuberculosis followed by lymph nodes and abdomen. Leukemias
      were the commonest neoplasm and SLE the commonest connective tissue disorder
      presenting with prolonged fever. Several fundamental observations were made in
      the study. Infections are the commonest cause of prolonged fever in our
      community, neoplasms and connective tissue disorders are also not rare. Secondly,
      patients with temperature between 100 to 101 degrees F should not be denied
      evaluation with the apprehension of unnecessarily investigating for habitual
      hyperthermia, as the condition was distinctly rare in the series. Thirdly,
      analysis of materials from organs or systems suspected to be abnormal clinically
      or by simple imaging techniques had high diagnostic yield. Finally, usual causes
      of prolonged fever are illnesses ordinarily encountered in clinical practice,
      pyrexia becomes protracted either because the presentation is atypical or
      incomplete, or because we fail to make proper use of available clinical or
      paraclinical information.

PMID- 9037844
TI  - An analytic study of surgical management of the temporomandibular joint
      ankylosis: an experience in Bangladesh.
AB  - The clinical observations on 14 cases of temporomandibular joint (TMJ) ankylosis
      including age and sex incidences as well as surgical management are presented in
      this paper. Ankylotic TMJ arthroplasty which include condylectomy with or without
      interpositional materials such as auricular cartilage and temporalis muscle flap
      to prevent reankylosis was used as the corrective measure. The accessory
      procedures like costochondral grafts and saggital split osteotomy to restore
      ramus height accompanied by camouflaging genioplasty in some of these cases were
      carried out. Besides, bilateral concomitant coronoidectomy were done in all
      cases. The patients were divided in three groups. In four cases only condylectomy
      was performed; the result was poor in three cases and moderate in one case.
      Condylectomy accompanied by interpositioning of auricular cartilage was done in
      another four patients; the result was poor in one case, moderate in one case and
      good in 2 cases. Six subjects were treated with condylectomy along with
      interpositioning of temporalis muscle flap; the result was good in 5 and moderate
      in 1 case. Condylectomy with temporalis muscle flap appeared to be the best
      method for TMJ ankylosis.

PMID- 9037846
TI  - The effect of physical fitness on intraocular pressure in Chinese medical
      students.
AB  - BACKGROUND: Virtually all the tissues and systems of the human body have been
      shown to be responsive to programs of exercise. Regarding the relationship
      between physical fitness and intraocular pressure (IOP), the existing literature
      is controversial with some associations inconsistent. In one study, IOP values
      were not dependent upon changes in physical fitness. In contrast to this, another
      study demonstrated that physical fitness significantly reduces intraocular
      pressure levels. In recent years it has been noted that intraocular pressure is a
      dynamic function and is subject to many influences both acutely and over the long
      term. The variety of results of previous studies may have come from several
      factors which can affect intraocular pressure. The present study was planned to
      investigate the effects of physical fitness on intraocular pressure in Chinese
      medical studies, after elimination of other affecting factors. METHODS: Forty
      medical students were categorized into control and experimental groups, each
      consisting of 20 subjects. The experimental group took a supervised exercise
      program for 10 weeks. Physical fitness was evaluated by measurement of maximum
      oxygen uptake with a Beckman O2 analyzer. Intraocular pressure was measured with
      the Goldmann applanation tonometer. RESULTS: After exercise training, the
      experimental group showed a marked increase in physical fitness. The difference
      of IOP between the control and experimental groups before exercise conditioning
      was 0.3 +/- 0.1 mmHg (P > 0.05). After 10 weeks, this difference increased to 1.1
      +/- 0.4 mmHg (p < 0.05). CONCLUSIONS: This study concludes that physical fitness
      reduces intraocular pressure. Whether exercise conditioning has a role as a
      nonpharmacologic approach or as an addition to medical therapy must be left to
      future investigations.

PMID- 9037845
TI  - Risk factors, endothelial cell turnover and lipid transport in atherogenesis.
AB  - Cardiovascular diseases remain to be the 4th rank of top ten causes of mortality
      in Taiwan in recent years. Atherosclerosis and coronary artery disease, which
      often culminating in the occurrence of myocardial infarction and congestive heart
      failure, are responsible for the majority of these death. One of the prominent
      features of atherosclerotic lesion is local accumulation of lipids, mainly in the
      forms of cholesteryl ester and free cholesterol, either within cells or
      extracellularly in matrix. Repeated endothelial injury and enhanced lipid
      infiltration are critical events in the development of atherosclerosis. Plasma
      lipoproteins may enter the arterial wall through endothelium, either
      transcellularly via vesicular transport or paracellularly via intercellular
      junction. Our previous studies have demonstrated that most of the arterial
      endothelial cells in mitosis are associated with the leakage of fluorescently
      labeled albumin and low density lipoproteins. Subsequently, such transendothelial
      leakage of macromolecules is also shown to be associated with endothelial cell
      death as assessed by immunocytochemical staining for IgG. These findings
      suggested that transiently leaky junctions occurring during endothelial cell
      turnover may provide potentially important pathways for increasing transport or
      leakage of macromolecules, including atherogenic LDL, across the vascular
      endothelium. Electron microscopic study using horseradish peroxidase as a tracer
      revealed markedly widening of intercellular junctions around endothelial cells in
      mitosis providing direct evidence in support of "cell turnover-leaky junction"
      theory for the localization of atherogenesis. Hypertension, smoking, diabetes,
      and hyperlipidemia are well-known major risk factors for atherosclerosis and
      coronary heart disease. In a series of investigations, we examined the hypothesis
      that hypertension smoking, diabetes, and hyperlipidemia increase the arterial
      endothelial cell turnover and hence transendothelial macromolecular transport,
      which may have some implications in increasing lipid entry and thus, accelerating
      atherogenesis. Animal experiments were performed in adult male spontaneously
      hypertensive rats (SHR), Wistar-Kyoto (WKY) normotensive rats, and Sprague-Dawley
      (SD) rats. SHRs were used as hypertensive group with WKY rats as normotensive
      control. SD rats were given nicotine at a dose of 5 mg/Kg body wt/ day in their
      drinking water to mimic smoking effect over a period of 6 weeks. Diabetes was
      induced in SD rats by single intraperitoneal injection of 60 mg/Kg body wt of
      streptozotocin. The duration of diabetes was 6 weeks. Also, SD rats were fed a
      diet containing 5% cholesterol for 6 weeks to induce hyperlipidemia. Age-matched
      rats of comparable number served as control for each experimental group. In en
      face preparations of thoracic aorta, mitotic endothelial cells were identified by
      hematoxylin staining, immunoglobulin G-containing dying or dead endothelial cells
      were detected by an indirect immunoperoxidase method, and endothelial leakage to
      Evans blue-albumin (EBA) complexes (5 minutes after intravenous injection) was
      visualized and quantified by fluorescence microscopy. The results showed that
      SHR, chronic oral nicotine-treated rats, diabetic, rats, and hyperlipidemic rats,
      when compared to control rats, had higher values for the frequency of endothelial
      cell death and the number density of EBA leaky foci in the aorta. These findings
      suggested that hypertension, cigarette smoking, diabetes mellitus, and
      hyperlipidemia become risk factors in atherogenesis by increasing the rate of
      arterial endothelial cell turnover and the associated endothelial cell turnover
      and the to the consequent enhanced entry of atherogenic lipoproteins into the
      arterial wall and accelerated atherogenesis.

PMID- 9037847
TI  - Antianginal and anti-ischemic efficacy of nisoldipine in stable angina pectoris:
      a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Nisoldipine, a dihydropy ridine calcium antagonist, is a potent
      vasodilator with selectivity for the coronary tree. The purpose of the study was
      to evaluate the onset and duration of antianginal and anti-ischemic efficacy of a
      single oral dose of nisoldipine compared with placebo in patients with stable
      angina pectoris. METHODS: In 33 patients with stable angina pectoris, nisoldipine
      was tested (10 mg daily) in a randomized, double-blind, placebo-controlled study.
      Drugs having antianginal and anti-ischemic effects (except sublingual
      nitroglycerin) were withdrawn Patients underwent a four-day "washout" phase, then
      were randomly assigned to nisoldipine (10 mg daily) or placebo for six days. On
      Day 4 and Day 10, three times of treadmill exercise testing were performed before
      daily medication was given, 2 hours and 6 hours after dosing, respectively.
      RESULTS: Twenty-eight patients (14 taking nisoldipine and 14 taking placebos
      completed the study and were included in the statistical evaluation. Compared
      with placebo, total exercise duration increased significantly during all three
      sequential exercise testing in patients receiving nisoldipine. The frequency of
      anginal attacks decreased significantly while patients were receiving nisoldipine
      (0.29 +/- 0.44/patient/ day versus 0.14 +/- 0.26/patient/day, p < 0.05).
      Similarly, there was a trend toward a decrease in the consumption of sublingual
      nitroglycerin while patients were receiving nisoldipine. Adverse effects were
      mild. CONCLUSIONS: The study confirms that nisoldipine is an active antianginal
      and anti-ischemic agent, with an acceptable side effect profile when used as
      monotherapy. The anti-ischemic effect lasted more than six hours and the drug
      could be administered once daily.

PMID- 9037848
TI  - Effect of quinapril therapy on blood pressure and serotonin change in patients
      with mild to moderate hypertension.
AB  - BACKGROUND: Previous studies have shown that serotonin plays an important role in
      hypertension because of its vasoconstrictive effect, mediated through
      serotonergic receptors. Angiotensin-II is a potent vasopressor which facilitates
      the aggregation of platelets, subsequently releases serotonin. Because quinapril
      is an angiotensin-converting enzyme inhibitor and could result in a decrease of
      angiotensin-II, Quinapril was used to treat patients with mild or moderate
      hypertension in order to observe the change of plasma serotonin. METHODS: Twenty
      two patients, (10 males, 12 females, mean age 45 yrs) without other major medical
      diseases and secondary causes of hypertension, were selected for this study. High
      performance liquid chromatography (HPLC) with electrochemical detection was used
      to detect the plasma serotonin. These patients were given placebos for two weeks
      before the first dose of quinapril (5 mg). Thereafter, the dosage was adjusted
      according to the response of blood pressure to a desired value (BP < 140/90
      mmHg). At about 14:00 hours on the first day, after the patient had rested for an
      hour and was in a quiet condition, blood was drawn by venipuncture with heparin
      as anti coagulant; the plasma serotonin concentration was determined for the
      baseline value. The plasma serotonin level was rechecked eight weeks later.
      RESULTS: It was found that systolic blood pressure began to decrease
      significantly two weeks after quinapril therapy, and then reached a constant
      state. Blood pressure decreased from 174/107 mmHg to 134/87 mmHg. Among these 22
      patients, there were 14 (65%) whose blood pressure reduced to a normal range.
      Plasma serotonin also decreased significantly from 4.69 +/- /3.67 ng/ ml to 2.89
      +/-2.64 ng/ml (p < 0.05). According to this data, 15 in 22 patients (68%) had
      reduction of plasma serotonin. There was little correlation between change in
      blood pressure and change of plasma serotonin; the correlation co-efficiency is
      only 0.019. CONCLUSIONS: This study shows that quinapril has an antihypertensive
      property and serotonin-lowering effect. Since there was no correlation between
      the change of serotonin and blood pressure, these two actions of quinapril might
      have been mediated through different mechanisms.

PMID- 9037849
TI  - The efficacy of percutaneous transluminal angioplasty in the treatment of failing
      vascular access in chronic hemodialysis patients.
AB  - BACKGROUND: Failure of vascular access leading to inefficient hemodialysis is the
      most common cause of morbidity in uremic patients. Careful observation of
      clinical signs and hemodynamic monitoring are vitally important to prevent
      complete fistula thrombosis. This study was undertaken to evaluate approaches for
      early detection and the application of percutaneous transluminal angioplasty in
      the treatment of failing vascular access. METHODS: From August 1994 to August
      1995, 32 uremic patients with failing vascular access (26 native arteriovenous
      fistulas, 6 polytetrafluroethlene (PTFE) grafts), presented signs of poor
      arterial flow, high venous pressure, significant recirculation, acute fistula
      thrombosis and persistent swelling of the access arm. These patients underwent
      fistulography and subsequent angioplasty in the confirmed obstructed sites.
      RESULTS: Thirty-seven angioplasty procedures were performed including 32 de novo
      lesions and 5 restenotic lesions; of the total, 32 (86.5%) were successful. In
      native arteriovenous (AV) fistulas, the most common problem was inadequate flow
      with the lesion located within 5 cm from the AV junction (63.6%). In PTFE grafts,
      the most common presentation was high venous pressure with the lesion located at
      the PTFE-venous junction (57.1%). CONCLUSIONS: Through clinical surveillance and
      hemodynamic monitoring during hemodialysis, failing vascular access can be
      detected early and treated effectively with percutaneous transluminal
      angioplasty.

PMID- 9037850
TI  - A model for investigating effect of shock waves on intracellular calcium
      mobilization.
AB  - BACKGROUND: Shock wave lithotripsy (SWL) has become a non-invasive standard
      treatment for urolithiasis; however, it has some unwanted bioeffects. A cell
      model using calcium (Ca) imaging of cultured Madin-Darby canine kidney (MDCK)
      cells has been established in this laboratory to study the effects of shock waves
      on intracellular free Ca mobilization of renal tubular cells. METHODS: Digital
      video imaging of fura-2 fluorescence was used to measure both resting and
      stimulated intracellular free Ca concentrations in single cultured MDCK cells.
      Pharmacological agents including adenosine-5'-trisphosphate (ATP), bradykinin and
      thapsigargin, were used as Ca mobilizing agents. RESULTS: ATP, bradykinin and
      thapsigargin all elicited a robust transient increase in intracellular Ca
      concentration. CONCLUSIONS: A cell model was established to investigate the
      effect of shock waves on single kidney cells. This provided an opportunity to
      determine how shock waves affect the regulation of intracellular Ca
      concentrations in kidney cells; in addition, it allows investigation, for the
      first time at the single cell level, of whether blocking Ca entry in kidney cells
      plays any role in the mechanism by which some Ca channel blockers, e.g.
      nifedipine and verapamil, protect patients of urolithiasis from shock wave
      induced renal damage.

PMID- 9037851
TI  - Lunate and perilunate dislocation.
AB  - BACKGROUND: Perilunate dislocation is an uncommon injury of the wrist due to
      hyperextension. The factors affecting its prognosis are still controversial. The
      aim of the present study was to review its fracture types, associated injuries,
      timing of surgery, different fixation methods and prognostic factors. METHODS:
      Fourteen patients with perilunate dislocation or fracture dislocation were
      treated by open reduction and internal fixation, and were followed for at least
      12 months. A functional scoring system and X-ray findings were used for follow-up
      evaluation. RESULTS: Two patients had excellent results, six patients had good
      results, and four had fair results. Only two patients had poor results. Treatment
      delayed over one month, transscaphoid perilunar fracture dislocation, or fixation
      of the transscaphoid fracture with Kirschner wire was associated with poorer
      results. CONCLUSIONS: Early diagnosis of perilunate dislocation, prompt open
      reduction and rigid fixation for fracture combined with ligament repair can give
      more promising results.

PMID- 9037852
TI  - Acute monteggia fractures in children.
AB  - BACKGROUND: Monteggia fracture rarely occurs in children. If it occurs, type I
      fracture is most commonly seen. We study the functional results of nonsurgical
      management in acute cases. METHODS: From July, 1988 through October, 1994, we
      encountered 15 cases of acute Monteggia fractures, accounting for 2.3% of forearm
      fractures. Twelve were males and three were females, at an average age of 7 years
      and 10 months. Nine fractures occurred on left non-dominant side, six occurred on
      right dominant side. There were eleven type I (73.3%), no type II, three type III
      (20%), and one type IV (6.7%) fractures. All of these patients received closed
      reduction with long arm casting, and the most stable position of fracture was
      supination of the forearm and flexion of the elbow. RESULTS: After follow-up for
      an average of 45.9 months, all fractures were found to unite without residual
      deformity of ulna or dislocation of the radial head. The functional results were
      excellent. Posterior interosseous nerve palsy occurred in one patient before
      treatment, and recovered spontaneously. CONCLUSIONS: Unlike adults, children with
      Monteggia fractures can get excellent results from closed reduction with long arm
      casting.

PMID- 9037853
TI  - Hypercapnic respiratory acidosis precipitated by hypercaloric carbohydrate
      infusion in resolving septic acute respiratory distress syndrome: a case report.
AB  - Complications may occur when nutritional support is administered either
      parenterally or enterally. Inappropriate nutritional formulas with high
      carbohydrate loads can precipitate respiratory failure in patients with
      compromised lung function, induce respiratory distress which manifests as dyspnea
      and tachypnea in an originally normal lung condition, produce hypercapnic
      acidosis in mechanically ventilated patients with chronic obstructive pulmonary
      disease (COPD) as well as patients recovering from acute respiratory distress
      syndrome (ARDS) without chronic lung disease, or result in difficult weaning.
      Hypercaloric mixed substrates administered either parenterally or enterally can
      also have profound impacts on gas exchange and energy expenditure. This report
      describes a patient who experienced exacerbation of respiratory distress and
      hypercapnic acidosis during recovery from septic ARDS as the result of a
      nutritionally-related increase in CO2 production. As carbohydrate calories were
      decreased, CO2 production diminished and the hypercapnia was resolved. The
      importance of indirect calorimetry cannot be overemphasized during tailoring of
      nutritional support for the critically ill patients.

PMID- 9037854
TI  - Intravenous immunoglobulin therapy in POEMS syndrome: a case report.
AB  - One course of intravenous immunoglobulin was tried on a patient with the syndrome
      of polyneuropathy, organomegaly, endocrinopathy, M-protein and skin lesions and
      Castleman's disease. No effect was noted.

PMID- 9037855
TI  - Persistent lung uptake in the redistribution phase of Tl-201 chloride myocardial
      SPECTs--a sign of severe pulmonary edema: a case report.
AB  - Assessment of thallium (Tl)-201 chloride myocardial stress and rest single photon
      emission computed tomography (SPECT) includes left ventricular defects, left
      ventricular dilation, and pulmonary uptake. Lung uptake is associated with severe
      coronary artery disease or reflects transient left ventricular dysfunction and
      provides poor long-term prognosis. On redistribution imaging, lung activity
      should be absent or decreased relative to the myocardial activity. A patient with
      persistent Tl-201 uptake upon redistribution imaging due to lung edema secondary
      to congestive heart failure is reported. One should be aware that pulmonary
      edema/congestive heart failure can cause an increase in pulmonary uptake which
      persists in redistribution imaging.

PMID- 9037856
TI  - Pelvic inflammatory pseudotumor with central infectious abscess: a case report.
AB  - Inflammatory pseudotumors (IPT) are a fascinating group of lesions which involve
      almost all organs and tissues of the body. The clinical manifestations are
      diverse. Final diagnosis can only be made by meticulous microscopic examination
      of different areas of the tumor. A 60 year-old woman had a pelvic IPT with
      central infectious abscess. The lesion involved her urinary bladder, mesentery,
      terminal ileum, right rudimentary ovary and the abdominal wall. It mimicked
      malignant tumor clinically, and led to total surgical excision. Early follow-up
      has shown a favorable results. IPTs are extremely uncommon. The characteristic
      pathologic picture is a reparative fibroblastic tissue infiltrated by polymorphic
      inflammatory cells. Pelvic IPT, admixed with central infectious abscess, is even
      rarer. Prior pelvic surgery and pasteurella hemolytica infection might be
      causative factors in this reported case.

PMID- 9037858
TI  - [Purification of EcoO44I restriction endonuclease in Escherichia coli O44
      isolated from an affected human].
AB  - A restriction endonuclases (ENase) designated EcoO44I was purified without non
      specific nucleases from enteropathogenic Escherichia coli O44 Hiromi strain of
      affected human origin. The yield was 1, 100 units/g of wet cells. The EcoO44I
      ENase recognized and cleaved the specific sequence of 5'-GGTCTC-3' (1/5) as was
      the case with Eco31I or BsaI ENase. Because of the stability and high yield,
      EcoO44I would be useful for recombinant DNA technology after isolation of EcoO44
      positive, avirulent mutant strains of E. coli O44 Hiromi.

PMID- 9037857
TI  - [The use of biotechnological recombinant-mice in biological safety research].
AB  - Number of transgenic and knock-out mice increased rapidly during the last decade.
      This review article describes a potential usefulness of transgenic and knock-out
      mice for biological safety research with respect to each toxicological category
      for safety evaluations, such as studies for carcinogenicity, general toxicology,
      genotoxicologic testing, and immuno-toxicological evaluations. In the
      carcinogenicity, a possible model required for a short-term study in
      carcinogenicity was discussed. Further, a couple of future subjects were focused
      specifically on the biotechnology-derived pharmaceuticals and the biotechnical
      recombinant-mice as a second generation, i.e. experimental mice with double or
      multiple gene-recombination. Those usefulnesses were also introduced briefly.
      Establishing the biotechnical recombinant-mice for each safety testing
      contributes not only to simplify and qualify the on-going evaluation system, but
      also to the traditional animal studies to be re-evaluated, so that the solutions
      may lead them to a future in vitro-alternative system much smoothly. For general
      references, historical reviews on the biotechnical recombination in experimental
      animals were also briefly introduced to elucidate a new broad area in
      developmental biology.

PMID- 9037859
TI  - [Teratogenicity study of magnesium chloride hexahydrate in rats].
AB  - Teratogenicity of magnesium chloride hexahydrate (MgCl2.6H2O) was examined in
      rats. Magnesium chloride hexahydrate dissolved in distilled water was given to
      pregnant Wistar rats by gavage once a day from day 6 through 15 of pregnancy at
      doses of 0, 200, 400 and 800 mg/kg/day. The pregnant rats were sacrificed on day
      20 of pregnancy and their fetuses were examined for malformation. Magnesium
      chloride hexahydrate caused no increased incidences of fetal malformation, and no
      toxic signs in the pregnant rats and the fetuses. It was concluded that magnesium
      chloride hexahydrate has no teratogenicity in rats when given by gavage. The no
      observed adverse effect level was estimated to be over 800 mg/kg/day for both
      pregnant rats and rat fetuses.

PMID- 9037860
TI  - [Intensity of liver tumor promotion effects in rats given repeated oral
      administrations of benzimidazole compounds].
AB  - Liver tumor-promoting effects of anthelminthic agents, febantel (Feb),
      fenbendazole (Fen) or oxfendazole (Oxf), were investigated in a rodent 2-stage
      carcinogenesis model. Five-week-old male F344 rats were initiated with or without
      diethylnitrosamine (DEN) and one week later given diet containing Fen (3600,
      1800, 600, 200 or 70 ppm), Feb (2000, 1000, 500 or 100 ppm) or Oxf (500, 250, 100
      or 10 ppm) for 8 weeks. Induction of CYP1A1/2 was observed in treated groups of
      DEN + Feb and DEN + Oxf groups, and its induction was most marked in DEN + Oxf
      groups. CYP2B1 and CYP4AI were also induced in these treated groups. The number
      or area of Cx32 positive spots per hepatocyte was significantly decreased in
      treated groups except for DEN + Oxf 100 ppm group, as compared to DEN alone
      group. GST-P positive foci was significantly increased in DEN + Fen groups
      treated with 1800 ppm or more, DEN + Feb groups treated with 1000 ppm Feb or more
      and DEN + Oxf groups treated with 250 ppm Oxf or more. These results suggest that
      these three compounds have liver tumor promotion effects and the promoting action
      in Oxf is most strong among them.

PMID- 9037861
TI  - [A 13-week subchronic toxicity study of gardenia blue in F344 rats].
AB  - A 13-week oral toxicity study of gardenia blue was performed in male and female
      F344 rats at the dose levels of 5.0, 2.5, 1.25, 0.6 and 0% in the diet, to
      determine the maximum tolerable dose (MTD) for subsequent investigation of
      carcinogenicity. Rats were randomly allocated to 5 groups, each consisting of 10
      males and 10 females. No groups showed decreases in body weight gain and food
      intake, and all animals survived until the end of the experiment. A dose
      dependent decrease in number of platelets was observed in females treated with
      gardenia blue in hematological examination, but not in males. No
      histopathological change, relating to the treatment, in megakaryocyte which is
      the progenitor cell of platelets was observed in the treated-females. Serum
      biochemistry revealed increases in GOT and GPT in both sexes treated with the
      5.0% and 2.5% gardenia blue, as compared to the control value. However, these
      were not considered to be specific changes because of lack of any clear dose
      response. In addition, no histopathological changes indicating obvious toxicity
      of gardenia blue were observed in the liver of both sexes treated with gardenia
      blue. Based on these data, the MTD of gardenia blue for both sexes in F344 rats
      was considered to be 5.0% or more in the diet.

PMID- 9037862
TI  - [Modifying effects of goitrogens on the tumor development in the liver and lung
      of rats].
AB  - In order to investigate whether goitrogens and liver enzyme-inducers modify the
      tumorigenesis in the liver or lung, 6-week old male F344 rats were given single
      subcutaneous injection of DHPN, and starting one week later received water
      containing goitrogens, namely sulfadimethoxine (SDM), propylthiouracil (PTU) and
      potassium thiocyanate (KSCN), or an enzyme-inducer, phenobarbital (PB), for 19
      weeks ad libitum. Although the number of GST-P positive foci in the liver was
      significantly increased in the PB group as compared to the control group, there
      were no significant fluctuations in the SDM, PTU and PB groups. With respect to
      the lung, it is suggested that SDM, KSCN and PB may enhance the lung
      tumorigenesis, since the multiplicities of hyperplasias of alveolar epithelia
      were increased in groups treated with these compounds.

PMID- 9037863
TI  - [Analysis of components in natural food additive "grapefruit seed extract" by
      HPLC and LC/MS].
AB  - The components in a commercial natural food additive "Grapefruit seed extract"
      and the ethanol extract of grapefruit seeds were analyzed by HPLC and LC/MS. The
      HPLC chromatogram of the commercial grapefruit seed extract was quite different
      from that of the ethanol extract of grapefruit seeds. Three main peaks were
      observed in the chromatogram of the commercial grapefruit seed extract. By
      comparison of the retention times and the absorption spectra with those of
      authentic samples, two peaks were ascribed to methyl-p-hydroxybenzoate and 2,4,4'
      trichloro-2'-hydroxydiphenylether (triclosan). Triclosan was also identified by
      LC/MS by using the negative electrospray ionization method.

PMID- 9037864
TI  - [Annual daily intakes of Hg, PCB and arsenic from fish and shellfish and
      comparative survey of their residue levels in fish by body weight].
AB  - We have been surveying toxic substances in food and foodstuffs and carrying out a
      total diet study on the intakes of various substances since 1979 in cooperation
      with local public institutes in Japan. In this paper, we report the daily intakes
      of mercury, PCB and arsenic from foods, and the relation between the
      concentrations of these substance in fish and the fish body weight. The intakes
      of mercury and arsenic were 6.9-11.0 micrograms/ man/day and 120-230
      micrograms/man/day, respectively. The intakes of these substances remained on a
      stable level from 1979 to 1994. On the other hand, the intake of PCB decreased
      from 3.1 micrograms/man/day in 1979 to 0.9 microgram/man/day in 1994. Most of the
      intakes of mercury, PCB and arsenic were derived from the diet group "fish and
      shellfish". The level of mercury in fish increased with increasing fish body
      weight. For PCB and arsenic, there was no correlation between these
      concentrations in fish and the fish body weight, except that mackerel and croaker
      show a higher concentration of PCB when they are small. Arsenic shows almost a
      constant level in each fish regardless of their body weight.

PMID- 9037865
TI  - [Preliminary screening for antiviral AIDS drugs. VI. Report for fiscal year
      1993].
AB  - Preliminary screening of antiviral AIDS drugs has been carried out using three
      different in vitro assay systems. Among 138 samples tested, two were found to
      inhibit the growth of HIV in vitro. Neither of the positive samples has hopeful
      signs, as the ranges of effective doses of the samples are very narrow.

PMID- 9037866
TI  - [Preliminary screening for antiviral AIDS drugs. VII. Report for fiscal year
      1994].
AB  - Preliminary screening of antiviral AIDS drugs has been carried out using three
      different in vitro assay systems. Among 246 samples of different origin tested,
      six were shown to inhibit the growth of HIV in vitro. Two of the positive samples
      have hopeful signs, as the ranges of effective doses are wider than those of most
      of positive samples which had been found by us.

PMID- 9037867
TI  - [NIHS information and computing infrastructure (NICI)].
AB  - We describe the information and computing infrastructure in National Institute of
      Health Sciences, which were constructed until May, 1996. The in house computer
      network and computing facilities for common usage in NIHS have been developed
      under the initiative of Division of Chem-Bio Informatics since 1989. The present
      LAN (Local Area Network) consists of coaxial cables and optic fibers which are
      connected by a LAN Switch. The LAN is connected to the Internet via IMnet, the
      inter ministry network back bone of the Science and Technology Agency. Various
      types of workstations and personal computers such as SUN WS, Silicon Graphics WS,
      IBM WS & PC, Macintosh, and NEC PC are connected to the LAN. This computing
      network environment which we named NICI (NIHS Information and Computing
      Infrastructure) not only provides network communications but also facilitates
      advanced computating systems for chemical safety research at NIHS as a COE.

PMID- 9037868
TI  - [Development of a base system for information dissemination of the Internet].
AB  - The development of information and computing infrastructure at NIHS (NICI),
      enabled us to provide a good environment for storing information that can be
      accessed by the Internet. Information can be stored either on WWW servers or on
      databases. All databases were developed on PC using database management systems
      such as 4th Dimension or Access, and were transferred to a UNIX machine with the
      database management system Sybase. A tool for accessing databases via the WWW
      (Web) was developed. This interface program used a freeware called Genera. Tools
      were also implemented for handling the so called VRML worlds.

PMID- 9037869
TI  - [A structure based pharmaceutical database for drug interactions].
AB  - A structure-based pharmaceutical database for drug interactions has been
      developed. This database is based on the ISIS/Desktop and the Microsoft Access
      relational database system for Windows. Data of Japanese accepted name, molecular
      formula, molecular weight, CAS registry number, therapeutic category index code,
      structural formula, Japan ethical drugs code, side effects information, drug
      interactions information were taken from "Japanese Accepted Names for
      Pharmaceuticals 1992", "Drugs in Japan Ethical Drugs 1993" and "Drug Intelligence
      Reinforce".

PMID- 9037870
TI  - [An international exchange and dissemination of chemical safety information on
      the Internet].
AB  - An information system for chemical safety has been developed on the National
      Institute of Health Sciences (NIHS) Information and Computing Infrastructure. The
      system is based on client server systems on the local area network (LAN)
      connected to the Internet. A wide range of safety information for chemicals
      including foods, food additives, household goods, industrial chemicals and
      environmental pollutants were collected and put on the World Wide Web (WWW)
      server and the database management system, Sybase. In addition to original
      information contents, the System has links to many useful Web sites so that it
      functions as a global hub for chemical safety information.

PMID- 9037871
TI  - [Dissemination of drug information on the Internet].
AB  - We developed the system of the guide for the drug and the relevant information by
      using the database on the Internet. We set up a site of drug information (Drug
      Info Guide). This system enabled pharmaceutical and medical staff to easily
      access the latest drug information. Further, we attempted to promote the exchange
      of the information regarding the safety and the efficacy of drugs among them.

PMID- 9037872
TI  - [Concise International Chemical Assessment Document (CICAD): a new chemical
      safety series in IPCS, internationalizing national reviews].
AB  - The Concise International Chemical Assessment Document or CICAD is a new chemical
      safety document series. It was launched by the IPCS in 1995, based on the
      decision of the International Forum on Chemical Safety in 1994, to
      internationally assess safety of 500 additional chemicals by the year 2000. The
      strategy to achieve this ambitious goal is to internationalize existing national
      assessment documents by rearranging contents of them into a standardized format,
      succinctly describing critical data, and adding international assessment process
      so as to be prepared efficiently, concisely and reliably. Critical review of
      document drafts by competent experts and input from countries including
      developing ones is required in the preparation. The author wishes to establish a
      framework to develop national reviews of chemical risk assessment domestically,
      while cooperating with this international programme.

PMID- 9037874
TI  - [Change of calibration method for enzyme assay in clinical biochemistry using
      automatic analyzer--comparison of calibration methods using K factor and human
      standard serum].
AB  - Enzyme activities in serum from experimental animals had been assayed by HITACHI
      7150 Automatic Analyzer using K factors for calibration. Because K factor is
      derived from a molar extinction coefficient and, reagent and sample volumes for
      each assay system, it is a constant value in usual assay. As an alternative
      calibration method, a human standard serum, which is commercially available and
      well-controlled, is presently used in the same assay system because of some
      difficulties in supply. Four serum enzymes of human, rat, dog and monkey sera
      were determined by the above two methods. All values calibrated by human standard
      serum were approx. 10% higher than that using K factors. These small differences
      are allowable because data calibrated by human standard serum can be compared
      with previous data given by K factors.

PMID- 9037873
TI  - [First drafts of the Environmental Health Criteria (EHC) circulated for comments
      by IPCS in 1995-1996].
AB  - Summaries of first draft of Environmental Health Criteria (EHC), which were
      circulated for comments by IPCS in the period of 1995-1996, are presented. EHC
      drafts on 9 compounds were received in this period.

PMID- 9037875
TI  - [Estimated production by the official inspection of coal-tar dyes (including dye
      aluminum lakes) in 1995].
AB  - The number of official inspection of coal-tar dyes and their lakes from April in
      1995 till March in 1996 were 580 in total. The quantity which passed inspection
      amounted to 166.4 ton in Japan. The production of color in each month was
      summarised in Table 1, and by each producing company in Table 2. The food coal
      tar dye produced in the largest quantity was Food Yellow No.4, occupying 43.9% in
      this period.

PMID- 9037876
TI  - [Sennosides Reference Standard (Control 951) of the National Institute of Health
      Sciences].
AB  - The "Sennosides Reference Standard (Control 951)" was prepared, which is intended
      to be used for the fluorophotometric assay of sennosides content in the
      preparation of "Sennosides". In this assay hydroxylated mono- and dianthraquinone
      glucosides are chelated with boric acid, and the fluorescence intensity of the
      chelate is determined against that of the Reference Standard (RS). In the
      establishment of this RS, sennosides content in the candidate material must be
      determined accurately by fluorophotometry. The Sennoside AB for assay, prepared
      as an equimolar mixture of the purified sennoside A and Sennoside B, was used as
      the RS for the fluorophotometry. Based on the above concept, sennosides content
      in the candidate was determined as calcium salts to be 60.1 +/- 1.6% by the
      fluorophotometry. Thus the sennosides content of this Sennosides RS was certified
      to be 60%. Separately, contents of Sennoside A (SA) and Sennoside B (SB) in this
      candidate were determined by using HPLC. As a result, the sum of SA and SB was
      estimated to be 38% as free acids. Thus it was suggested that about 20% of
      dianthraquinone glucosides other than SA and SB and anthraquinone glucosides may
      be included in this Sennoside RS as free acids. Analytical results on the USP
      Sennosides RS were also shown and discussed, compared with the present Sennosides
      RS.

PMID- 9037877
TI  - [Digitoxin Reference Standard (Control 951) of the National Institute of Health
      Sciences].
AB  - The raw material of digitoxin was tested for preparation of the "Digitoxin
      Reference Standard (Control 951)". Analytical data obtained were as follows: loss
      on drying, 0.0%; infrared spectrum, the same as that of the JP Digitoxin
      Reference Standard (Control 845); thin-layer chromatography, no impurity was
      detected; high-performance liquid chromatography (HPLC), two kinds of impurities
      were detected and the total amount was estimated to be 0.16 +/- 0.01% (n = 3);
      assay, 99.0% by HPLC. Based on the above results, the raw material was authorized
      as the JP Digitoxin Reference Standard (Control 951).

PMID- 9037878
TI  - [Betamethasone Reference Standard (Control 951) of the National Institute of
      Health Sciences].
AB  - The raw material of betamethasone was tested for preparation of the
      "Betamethasone Reference Standard (Control 951)". Analytical data obtained were
      as follows: loss on drying, 0.0%; infrared spectrum, the same as that of the JP
      Betamethasone Reference Standard (Control 845); thin-layer chromatography, no
      impurity was detected; high-performance liquid chromatography (HPLC), two kinds
      of impurities were detected and the total amount was estimated to be 0.16 +/-
      0.01% (n = 3); assay, 100.0% by HPLC. Based on the above results, the raw
      material was authorized as the JP Betamethasone Reference Standard (Control 951).

PMID- 9037879
TI  - [Tocopherol Acetate Reference Standard (Control 941) of the National Institute of
      Health Sciences].
AB  - The raw material of tocopherol acetate was tested for the preparation of the
      "Tocopherol Acetate Reference Standard (Control 941)". Analytical data obtained
      were as follows: infrared spectrum, the same as that of the Tocopherol Acetate
      Reference Standard (Control 919); specific absorbance, E1(1%)cm (284nm) = 44.5;
      thin-layer chromatography, no impurities were detected until 50.0 micrograms;
      high-performance liquid chromatography (HPLC), 2-3 impurities were detected and
      the amount was estimated to be about 1%; assay by HPLC, 100.8%. Based on the
      above results, the raw material was authorized as the Japanese Pharmacopoeia
      Reference Standard (Control 941).

PMID- 9037880
TI  - [Cyanocobalamin Reference Standard (Control 951) of the National Institute of
      Health Sciences].
AB  - The raw material of cyanocobalamin was tested for preparation of the
      "Cyanocobalamin Reference Standard (Control 951)". Analytical data obtained are
      as follows: loss on drying, 1.8%; infrared spectrum, the same as that of the JP
      Cyanocobalamin Reference Standard (Control 936); thin-layer chromatography, three
      impurities were detected; high-performance liquid chromatography (HPLC), eight to
      nine kinds of impurities were detected and the total amount of impurities was
      estimated to be 1.6 +/- 0.13% (n = 4); assay, 99.7% by spectrophotometry
      specified in the JP XII and 100.4% by HPLC, respectively. Based on the above
      results, the raw material was authorized as the JP Cyanocobalamin Reference
      Standard (Control 951).

PMID- 9037881
TI  - [dl-Camphor Reference Standard (Control 951) of the National Institute of Health
      Sciences].
AB  - The raw material of dl-camphor was examined for the preparation of the "dl
      Camphor Reference Standard". Analytical data obtained are as follows: ultraviolet
      spectrum, lambda max = 290 nm; infrared spectrum, the same as that of the present
      JP Camphor Reference Standard; melting point, 179.6 degrees C; purity test by gas
      chromatography (GC), three kinds of impurities were detected; assay by GC, 99.0%.
      Based on the above results, the candidate raw material was authorized as the JP
      Reference Standard (Control 951).

PMID- 9037882
TI  - [Lysozyme Reference Standard (Control 951) of the National Institute of Health
      Sciences].
AB  - The "Lysozyme Reference Standard (Control 951)" of the National Institute of
      Health Sciences was prepared. The lysozyme potency of the standard material was
      assayed against the Lysozyme Reference Standard (Control 915) by two
      turbidimetric methods using the drycells of Micrococcus luteus as the substrate.
      The potency of the standard material was in satisfactory agreement with that of
      Lysozyme Reference Standard (Control 915) and was defined as 1 mg [potency] per
      mg.

PMID- 9037883
TI  - [The Somatropin Reference Standard (Control 951) of the National Institute of
      Health Sciences].
AB  - Somatropin material was examined for preparation of the "Somatropin Reference
      Standard". The candidate material was evaluated by a domestic collaborative study
      in which eight laboratories participated. The protein content was determined to
      be 4.5 mg/Vial based on amino acid analysis. Because of the possibility of
      application as a chemical reference standard for assay by the HPLC method, a
      physico-chemical evaluation of the candidate material was also performed. By SE
      HPLC, the content of polymer, dimer were determined to be 0.54%, 0.98%,
      respectively. By RP-HPLC, the early peak area ascribed to desamido and sulfoxide
      form was 1.07% of the total peak area. And for informational data, the potency of
      the candidate material, being estimated by three different biological methods,
      weight gain assay, tibia test and adiposeconversion assay is 14.8 IU/vial. Based
      on the above results, the candidate was authorized as the Somatropin Reference
      Standard of the National Institute of Health Sciences.

PMID- 9037884
TI  - [Studies on "Fast Green FCF Standard" for the dye standard on the National
      Institute of Health Sciences].
AB  - The raw material for Fast Green FCF was tested for preparation of the "Fast Green
      FCF Standard (C.I. 42053)". Analytical data obtained were as follows: paper
      chromatography, only one spot is observed; arsenic content, 0.38 microgram/g;
      chloride content, 0.11%; sulfate content, 3.30%; heavy metals, lead, 8.0
      micrograms/g, manganese, 28.1 micrograms/g, and chromium, 1.6 micrograms/g;
      infrared spectra, 1575 cm-1, 1169 cm-1, and 1033 cm-1; loss on drying, 2.39%;
      assay, 93.0% by the titanium trichloride titration. Based on the above results,
      the raw material was authorized as the Dye Standard of National Institute of
      Health Sciences.

PMID- 9037885
TI  - [The Human Menopausal Gonadotrophin Reference Standard (Control 961) of the
      National Institute of Health Sciences].
AB  - Raw human menopausal gonadotrophin (HMG) material was examined for preparation of
      the "Human Menopausal Gonadotrophin Reference Standard (Control 961)". The
      candidate material was assayed its follicle stimulating hormone (FSH) activity
      and luteinizing hormone (LH) activity against the 3rd International Standard for
      FSH and LH, urinary (71/264) by the augmented ovarian weight gain assay and the
      seminal vesicle weight gain test, respectively. The potency of the new standard
      was defined as 56 international units of FSH activity per mg and 61 international
      units of LH activity per mg as the result of 13 and 5 assays, respectively, in
      four collaborative laboratories.

PMID- 9037886
TI  - [Assessment of bioequivalence].
AB  - Bioequivalence tests in Japan are now under the improvement according to the WHO
      guidance. This article describes the desirable assessment of bioequivalence where
      the use of discriminatory subjects, application of confidence interval methods,
      logarithmic transformation of pharmacokinetic data are recommended. The role of
      dissolution tests in bioequivalence assessment is also discussed.

PMID- 9037887
TI  - [Shelf-life estimation of pharmaceutical products by matrixing].
AB  - The shelf-life estimates of pharmaceutical products obtained by matrixing are
      compared with those obtained by ordinary analysis, using stability data generated
      by the Monte Carlo method. The effect of the variation in stability due to
      different packaging and formulations on the shelf-life estimates is described.
      Analysis of variance is proposed for the evaluation of shelf-life estimates
      obtained by matrixing. The relationship between the power of the test and the
      significance level is discussed as well as the effect of assay error on the power
      of test.

PMID- 9037888
TI  - [Determination of crude drugs in the pharmacopoeia].
AB  - The determination of crude drugs by high performance liquid chromatograph (HPLC)
      method was introduced to the Japanese Pharmacopoeia (JP) 12 for the first time.
      At JP 13, another HPLC methods were established for eight kinds of crude drugs
      and relative medicines. Special conception is used in the determination of crude
      drugs, different from chemical medicines. Determinations were classified to two
      methods: "assay" and "component determination" according to standards. "The
      Japanese Reference Standard" or "Reagent for assay" is used in assay, and
      "Reagent for component determination". is used in component determination. In
      addition, the analysis and the dryness of crude drug were discussed because they
      were important to evaluate the result of analysis exactly.

PMID- 9037889
TI  - [Application of thermal analysis to quality evaluation tests of drugs].
AB  - Thermal analysis method can be applied to the quality evaluation tests of drugs.
      Recent advances in the technology and the data-processing system on the apparatus
      have accelerated the utilization of this analytical techniques in the field of
      drug quality control. In this report, various application techniques of the
      thermal analysis such as DSC, DTA, TG and the impurity analysis by DSC, were
      reported and discussed from the viewpoints of a general test in the Japanese
      Pharmacopoeia. Further the present situations of this analytical method in the US
      Pharmacopoeia 23 and the British Pharmacopoeia 1993 are also explained.

PMID- 9037890
TI  - Elevated L-kynurenine level and its normalization by prednisolone in a patient
      with eosinophilia-myalgia syndrome.
AB  - We report a L-tryptophan-induced case of eosinophilia-myalgia syndrome in a
      Japanese woman and describe the time course of changes in tryptophan metabolism
      observed during steroid therapy. She had taken 1.0 g of the implicated L
      tryptophan daily. When admitted due to painful swelling of her extremities,
      eosinophil count was 22.3 x 10(9)/L. Before prednisolone treatment, her serum L
      kynurenine level was 10.2 mumol/L, a level about three-fold higher than the
      normal value, while serum tryptophan level was abnormally low (23.1 mumol/L). On
      the 14th day of prednisolone treatment (40 mg daily), L-kynurenine was declined
      to 8.1 mumol/L and, concomitantly, L-tryptophan level increased to the normal
      range (51.0 mumol/L). Subsequently, on the 42nd day of therapy, serum L
      kynurenine was normalized. In contrast, serum serotonin level was unchanged
      throughout the course of this therapy. Prednisolone dramatically reduced the
      elevated serum L-kynurenine with a reciprocal increase in serum L-tryptophan
      indicates that abnormal tryptophan metabolism, may play a role in the
      pathogenesis of eosinophilia myalgia syndrome, and that the observed effect of
      steroid treatment was due to suppression of elevated activity of indoleamine 2, 3
      dioxygenase, a first rate-limiting enzyme of the kynurenine pathway.

PMID- 9037891
TI  - Factor IX gene haplotypes in Amerindians.
AB  - We have determined the haplotypes of the factor IX gene for 95 Indians from 5
      Brazilian Amazon tribes: Wayampi, Wayana-Apalai, Kayapo, Arara, and Yanomami.
      Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5',
      nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron
      3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The
      results of the haplotype distribution and the allele frequencies for each of the
      factor IX gene polymorphisms in Amerindians were similar to the results reported
      for Asian populations but differed from results for other ethnic groups. Only
      five haplotypes were identified within the entire Amerindian study population,
      and the haplotype distribution was significantly different among the five tribes,
      with one (Arara) to four (Wayampi) haplotypes being found per tribe. These
      findings indicate a significant heterogeneity among the Indian tribes and
      contrast with the homogeneous distribution of the beta-globin gene cluster
      haplotypes but agree with our recent findings on the distribution of alpha-globin
      gene cluster haplotypes and the allele frequencies for six VNTRs in the same
      Amerindian tribes. Our data represent the first study of factor IX-associated
      polymorphisms in Amerindian populations and emphasizes the applicability of these
      genetic markers for population and human evolution studies.

PMID- 9037892
TI  - Correlations of quantitative chromosomal heteromorphisms and classic genetic
      markers to demogeographic data in Garfagnana valley (Tuscany, Italy).
AB  - The genetic structure and interrelationships of six populations of the Garfagnana
      valley (Tuscany, Italy) were examined using chromosomal heteromorphisms
      concurrently with blood group system, red cell isozyme, and serum protein
      polymorphisms, secretor status, and surname frequency data. We aimed to evaluate
      the relationship of cytogenetic polymorphisms to more classical sources of gene
      frequency data in a population with a well-known demographic scenario. The R
      matrix technique (Harpending and Jenkins 1973) was used to estimate kinship
      coefficients, and the Harpending-Ward model (1982) and its extensions for
      quantitative traits (Relethford and Blangero 1990) were used to detect
      differential systematic pressure among population subdivisions. Mantel statistics
      were used to assess the significance of the correlations between cytogenetic,
      genetic, isonymy, geographic, and migration matrices. The analyses consistently
      gave similar results for the DA/DAPI cytogenetic heteromorphism and most gene
      frequency data. Both sets of results depend on migration patterns and on
      geographic distance among population subdivisions. However, C cytogenetic
      heteromorphism and some separately analyzed genetic markers did not fit the
      demogeographic pattern. Overall, it appears that data from different levels of
      the genetic hierarchy (namely, DNA regions encoding for classical biochemical
      markers and the noncoding highly variable cytogenetic bands of heterochromatin)
      can be treated and compared using the same analytical tools.

PMID- 9037893
TI  - Characterization of four short tandem repeat loci (THO1, VWA31/A, CD4, and TP53)
      in northern Portugal.
AB  - Allele and genotype frequencies for two tetrameric and two pentameric short
      tandem repeat (STR) loci (THO1, VWA31/A, CD4, and TP53) were determined in a
      population sample from northern Portugal. Genotyping of PCR amplification
      products was done using polyacrylamide gel electrophoresis followed by silver
      staining; heteroduplex analysis was performed to distinguish THO1 genotypes
      involving allele 10 and the nonconsensus allele 9.3. For all loci allele
      frequencies fitted the distribution patterns generally observed in European
      populations. The observed genotype distributions do not deviate significantly
      from Hardy-Weinberg expectations, although for VWA31/A a significant excess of
      heterozygotes involving allele 17 was found. Mother-child pair analyses confirmed
      the regular Mendelian pattern of inheritance. Because the information content of
      these systems is high and because their genotyping is technically reliable and
      simple, CD4, THO1, VWA31/A, and TP53 are appropriate genetic systems for
      anthropological genetics.

PMID- 9037894
TI  - Genetic study of African populations: polymorphisms of the plasma proteins TF,
      PL, F13B, and AHSG in populations of Namibia and Mozambique.
AB  - Genetic variations of four highly polymorphic serum proteins, TF, PI, F13B, and
      AHSG, were tested to distinguish one black African and one Khoisan population of
      southwest Africa. The results show that indeed the systems TF, PI, and AHSG are
      of high value for anthropological genetics: The allele frequencies for these
      systems enable clear identification of and distinction between black African and
      Khoisan populations. The F13B locus, on the other hand, reveals for both the
      black African and the Khoisan populations specific and unique African variants: a
      high frequency of F13B*2 and the lowest frequency of F13B*3 so far worldwide. The
      new data are compared with results for TF and PI in another black African
      population of Mozambique, which Rodewald et al. (1988) had studied previously.
      The dendrogram, based on genetic distance data D and average linkage cluster
      analysis, shows minimal distance between both black African populations of
      Namibia and Mozambique and marked distance between those and the Khoisan
      population of Namibia.

PMID- 9037895
TI  - Sociobiology and HLA genetic polymorphism in hill tribes, the Irula of the
      Nilgiri hills and the Malayali of the Shevroy hills, south India.
AB  - Two endogamous tribes of Tamil Nadu, South India, the Irula of the Nilgiri hills
      and the Malayali of the Shevroy hills, were studied for their sociobiology and
      HLA polymorphism. For sociobiological studies 166 marriages in the Irula and 368
      marriages in the Malayali were recorded. The number and spatial distribution of
      patrilineal clans and their marriageable range (number of clans from which the
      brides came) were studied. Eight clans in the Irula and 16 clans in the Malayali
      were identified. Of these the Kuppar of the Irula and the Malayan of Malayali
      were the largest clans, and both of them had the greatest marriageable range. The
      numerical strength and the resultant spatial distribution correlated well with
      the marriageable range. HLA-A, B, and DR polymorphism was studied on 191 Irula
      and 42 Malayali following standard procedures. HLA typing revealed high
      frequencies (> 10%) of alleles HLA-A2, A9, A11, B17, B35, B40, DR2, and DR7 in
      both tribes, but the Irula had elevated HLA-A10, B8, and DR8 frequencies and the
      Malayali had elevated HLA-A31, B7, DR4, and DR5 frequencies. Two-locus haplotypes
      A10-B8 and A2-B5 were identified in both tribes, but A11-B40 and A2-B53 were
      present only in the Irula and A33-B44 and B15-DR6 were present only in the
      Malayali. The sociobiology of the Irula was correlated to the HLA genetic
      profile. The Irula sample was stratified based on clan and HLA data; The Kuppar
      clan was closer to the Kalkatti, the second largest clan, than to the Pungar and
      the Sambar clans. Thus the numerical strength and spatial distribution of various
      exogamous clans, presumably a result of migration during different periods of
      history, is reflected in the marriageable range and thus in the genetic distance.
      In studying HLA or any other genetic polymorphism of an endogamous tribe or
      caste, one needs to consider the social structure, spatial distribution, and
      marriageable range.

PMID- 9037896
TI  - Regional distribution of cystic fibrosis-linked DNA haplotypes in Brazil:
      multicenter study.
AB  - The restriction fragment length polymorphism (RFLP) haplotypes of cystic fibrosis
      (CF) alleles vary between populations. To determine the distribution of two RFLPs
      (XV-2C and KM-19) that are tightly linked to the CF locus, we analyzed a white
      sample from five different states of Brazil. The haplotypes of 314 CF- and 237
      non-CF-bearing chromosomes were uniformly distributed over the five states. The
      XV-2C allele and haplotype frequencies and the degree of linkage disequilibrium
      were determined. These were similar to values previously reported in southern
      European countries but different from results reported for northern and central
      Europe and North America. In contrast, although KM-19 allele frequencies differed
      between Brazilian states and European and North American countries, these
      frequencies were similar to values reported in black Americans. A significant
      proportion of Brazilian CF-bearing chromosomes had less common haplotypes,
      suggesting a heterogeneous distribution of CF gene mutations among Brazilians.
      Further studies are needed to identify the mutations affecting the Brazilian CF
      patients with various haplotypes.

PMID- 9037897
TI  - Association of retinol binding protein in multiple-case families with insulin
      dependent diabetes.
AB  - We performed a family study to investigate the heritability of reduced serum
      retinol levels observed in type 1 diabetes cases. Diet and serum factors,
      including retinol, total carotene, malondialdehyde, and retinol binding protein
      levels, were measured in 11 multiple-case families. The mean serum retinol level
      of the diabetics (46 ug/dl) was significantly less than the mean serum retinol
      level of the nondiabetics (60.9 ug/dl). The level of retinol binding protein was
      also significantly lower in diabetics (6.2 mg/dl) than in nondiabetics (7.6
      mg/dl). The serum values of retinol binding protein were closely related within
      families, including both diabetic and nondiabetic family members. A
      characteristic shared between diabetics and one-third of their family members was
      a low ratio of serum retinol to total carotene, suggesting a low conversion of
      dietary carotene into retinol. Analysis of food frequency reports showed no
      difference between dietary retinol or total carotene level in diabetics or their
      relatives. This study offers evidence that heritability and the reduced
      conversion of carotene may play a role in the level of serum retinol in type 1
      diabetes cases.

PMID- 9037898
TI  - Taste sensitivity to PTC and thyroid function (FT4 and TSH) in high- and low
      altitude Kirghiz populations in the Pamir.
AB  - PTC taste sensitivity distribution, determined using the Harris and Kalmus
      method, and analysis of thyroid activity using FT4 and TSH hormone assays were
      studied in a sample of 108 high-altitude subjects (3200 m) and in 90 lowlanders
      (900 m) from two different regions of Kirghizstan (Central Asia). All subjects
      were healthy Kirghiz males. In agreement with other available data on Kirghiz
      populations, a higher nontaster frequency was found in the high-altitude
      subjects. Furthermore, the results of our study indicate no association between
      thyroid function, PTC sensitivity, and age in both samples. No difference in
      thyroid function indicators was noted between highlanders and lowlanders.

PMID- 9037899
TI  - Population-based, genetically informative sample for studies of physical frailty
      and aging: black elderly twin study.
AB  - In this article 1 describe efforts to build a genetically informative, population
      based sample of black twins to study physical frailty and aging in the United
      States. This project involves the use of governmental registries combined with
      sampling techniques developed to overcome limitations in the registry data. Two
      analytical approaches to measures of disability are included to illustrate the
      types of questions that can be addressed with this sample. These results suggest
      that physical disability in late life has both genetic and environmental
      determinants. Only with a genetically informative sample can evidence be
      collected indicating that frailty may be driven by fixed processes (i.e.,
      disability resulting from activation of senescence genes), fluid processes (i.e.,
      disability resulting from changes in the features of the environment), or a
      combination of both.

PMID- 9037900
TI  - Genetic polymorphisms of orosomucoid ORM1 and ORM2 in Egyptians, Sudanese, and
      Qataris: occurrence of two new alleles.
AB  - Isoelectric focusing was used to investigate the genetic variants of the human
      plasma orosomucoid ORM1 and ORM2 gene loci in samples of Egyptians, Sudanese, and
      Qataris. The study populations were classified into 28 ORM phenotypes determined
      by 10 ORM1 and 9 ORM2 alleles that included 2 new alleles, designated ORM1*B13
      and ORM2*H21. Family studies of these new alleles are in accordance with
      codominant autosomal inheritance. A new interpretation for two previously
      reported alleles, ORM1*C6 and ORM2*H17, is also presented.

PMID- 9037901
TI  - Cardiac transplantation in South Carolina: the first 100 patients.

PMID- 9037902
TI  - Use of the gastroepiploic artery for coronary revascularization.
AB  - In summary, use of the gastroepiploic artery for coronary revascularization
      provides a reliable arterial conduit without increasing post-operative length of
      hospitalization, peri-operative morbidity or mortality. Reported mid-term patency
      rates exceed those of saphenous vein grafts and are comparable to internal
      thoracic artery grafts. Thus, the gastroepiploic artery is exceeded only by the
      internal thoracic artery as the preferable conduit in coronary revascularization.

PMID- 9037905
TI  - The hospital department of the AlMS House of Charleston.

PMID- 9037907
TI  - Why aren't doctors running show?

PMID- 9037906
TI  - "The care of the patient" revisited.

PMID- 9037908
TI  - Edward Jenner and vaccination.

PMID- 9037909
TI  - Designing a successful health fair to promote individual, family, and community
      health.
AB  - A health fair is a community health strategy used to meet community members'
      needs for health promotion, education, and prevention. In this article we focus
      on the importance of partnerships in designing a health fair; essential
      components; and steps in planning, implementing, and evaluating a health fair.
      The Healthy People 2000 framework can be used to guide the development of
      objectives and content for a health fair. We present a list of topics for
      exhibits and a Health Fair Evaluation Questionnaire used to measure outcomes of a
      health fair on participants' health beliefs and practices. Implications for
      nursing practice, education, and research include increasing nurses' awareness of
      community problems, health beliefs, and practices; networking opportunities that
      provide knowledge of new resources; service learning experiences for students;
      and opportunities for research on how health fairs meet health care needs and
      promote changes in health knowledge, beliefs, and practices.

PMID- 9037910
TI  - Foot care: an innovative nursing service in a community nursing center.
AB  - In this article we describe how providing regular foot care for the residents of
      public housing at an on-site nursing clinic has become a vital part of the
      clinic's services for the elderly and disabled residents. Good foot care
      contributes significantly to the health and well-being of elderly and at-risk
      groups of clients. With relatively little extra education for the nursing staff
      and for minimal cost, foot care can become an integral part of nursing services
      provided in many different types of community health settings. A framework for
      initiating and implementing a foot care program is highlighted.

PMID- 9037911
TI  - Introduction of wireless, pen-based computing among visiting nurses in the inner
      city: a qualitative study.
AB  - The purpose of this qualitative study is to understand how a sample of visiting
      nurses experienced the practice of home health nursing in the inner city and how
      they perceived the anticipated introduction of wireless, pen-based computing into
      their practice. Focus groups were held with visiting nurses 1 week before the
      introduction of the wireless, pen-based computers. The data were analyzed using
      Strauss and Corbin's (1990) method for concept development. The following central
      concepts emerged from the focus groups with visiting nurses: "Missing contact in
      the field," "Consumption of time writing on forms," "Using the computer to help
      with the practice of home health nursing," and "Home nursing is a lifeline."
      These concepts, based on the commentaries by visiting nurses, help one to
      understand the problems encountered by visiting nurses in the delivery of home
      health care, identify ways to incorporate evolving technologies to enhance
      nursing practice, and consider approaches to computer skill acquisition.

PMID- 9037912
TI  - Does home health care affect strain and depressive symptomatology for caregivers
      of impaired older adults?
AB  - The demands of providing care to impaired older adults frequently results in
      strain and depressive symptomatology. These outcomes of caregiving may be
      affected by social support such as home health care. Forty-nine caregivers to
      impaired older adults receiving home health care and 51 caregivers not receiving
      home health care were interviewed soon after identification by hospital personnel
      and 3 months later. Strain and depressive symptomatology were not significantly
      lower and positive caregiving appraisal was not significantly higher for
      caregivers receiving home health care even when controlling for their pretest
      measures. Strain and depressive symptomatology were significantly higher for
      caregivers of cognitively impaired persons. Home health care nurses need to
      identify those caregivers at greater risk to individualize services.

PMID- 9037913
TI  - Understanding mothers' perceptions of what is important about themselves and
      parenting.
AB  - The purpose of this article is to report what mothers of young adolescents
      perceive as important about themselves and parenting. Their perceptions were
      identified from brief written statements from a sample of 538 mothers of young
      adolescents. The women's statements were analyzed using content analysis
      techniques. Six themes emerged. Mothers described the challenges of putting their
      ideals about parenting into practice, including incorporating or discarding the
      influence of their own upbringing and the seeking of knowledge and skills to
      improve their parenting. Mothers described their values and goals. Feelings of
      self-doubt were made apparent through self-critical comments. Expressions of
      frustration were evident as were the serious life stressors managed by the
      sample. Repeated comments identified mothers' emphases on the importance of open
      family communication. Mothers had developed styles of parenting based on decision
      making methods and understanding the child's perspective. We suggest community
      health nurses use the themes as guidelines for anticipatory guidance with
      families during adolescence.

PMID- 9037914
TI  - HIV testing in the home.

PMID- 9037915
TI  - Dohi Memorial Lecture. Psoriasis--an immunological disease.

PMID- 9037916
TI  - Identification of mRNA-rich keratinocytes in the basal/suprabasal layers of
      psoriatic skin.
AB  - In this study, we examined the relative amounts of mRNA expressed in normal
      versus psoriatic epidermis, using in situ hybridization with a biotinylated
      oligonucleotide poly d(T) probe. The hybridization image was analyzed by Laser
      Scanning Confocal Microscopy (LSCM). In normal human skin, hybridization signals
      were detected homogeneously throughout the epidermis, mostly in nucleus. These
      signals disappeared following RNase T2 or RNase A treatment, indicating that the
      target for this probe is RNA; by implication, mRNA. In psoriatic lesions, the
      overall signal intensity was significantly elevated, especially in the
      basal/suprabasal layers. Moreover, those signals were most prominent in the
      cytoplasm, not in the nucleus. In contrast, the signals of uninvolved epidermis
      adjacent to the psoriatic lesions were indistinguishable from those of normal
      skin in both signal intensity and hybridization profile. Our data are consistent
      with the notion that one of the characteristic features of psoriasis is an
      elevated (or uncontrolled) synthesis of mRNA and proteins.

PMID- 9037917
TI  - The effect of methotrexate on the expression of a cysteine protease inhibitor
      (type 2 cystatin) in rat sebaceous glands.
AB  - The purpose of this study was to assess whether rat cystatin S, a cysteine
      proteinase inhibitor, is present in rat sebaceous glands, and to measure the
      effects of methotrexate on the expression of cystatin in these glands. With
      methotrexate treatment, the number of skin sebaceous cells expressing cystatin
      increased from 13.9% to 34.3% (P < .05). A smaller increase (from 15.3% to 23.9%;
      P = .1) was observed in Zymbal sebaceous glands. Type 2 cystatin could not be
      detected in the major salivary glands, nor in trachea, lung, stomach, small
      intestine, large intestine, spleen, liver, kidney, or pancreas, in any of the
      rats given either saline or methotrexate. Our results suggest that type 2
      cystatin is a constituent of normal sebaceous glands, and that the amount of
      cystatin present in these glands increases with methotrexate administration. We
      speculate that, in addition to the protective functions ascribed to sebaceous
      lipids, sebum may augment the physical barrier of skin through secretion of
      cysteine proteinases that may be pharmacologically modulated.

PMID- 9037918
TI  - Activity of eleven kampo formulations and eight kampo crude drugs against
      Propionibacterium acnes isolated from acne patients: retrospective evaluation in
      1990 and 1995.
AB  - We reviewed the susceptibility of Propionibacterium acnes to eleven Kampo
      formulations and to eight Kampo crude drugs that had been studied by examining
      their minimum inhibitory concentrations (MIC) in 1990 and 1995. P. acnes strains
      were most sensitive to Oren-gedoku-to (OGT) among these Kampo formulations.
      Coptidis Rhizoma (CR) and Phellodendri Cortex (PC) inhibited the growth of P.
      acnes significantly among the eight Kampo crude drugs examined. The patterns of
      distribution of MIC of Kampo formulations and Kampo crude drugs to P. acnes in
      this study were almost the same as in our previous report in 1990. No significant
      increases in MIC of Kampo formulations and Kampo crude drugs to P. acnes were
      observed. We speculated that Kampo crude drugs such as CR and PC, were better
      than minocycline or erythromycin from the point of view of a progressive increase
      in MIC to P. acnes. CR and PC, which were each an ingredient of OGT, might
      contain some components with strong antibacterial activity to P. acnes.

PMID- 9037919
TI  - Necrotizing fasciitis due to group A streptococci: a clinicopathological study of
      six patients.
AB  - The recent worldwide appearance of invasive group A streptococcal infections has
      again called attention to streptococcal necrotizing fasciitis. However, in
      contrast to polymicrobial necrotizing fasciitis, the streptococcal form has not
      been thoroughly studied clinically. The objective of the study was to elucidate
      the characteristic features of recent cases of necrotizing fasciitis due
      exclusively to pure group A streptococci. We encountered six patients with these
      criteria at a single hospital in Japan during the last 12 years. A
      clinicopathological analysis was performed in these six patients. In three
      patients, the clinical signs and the laboratory findings were characteristic of
      systemic toxicity. In this group, the clinical presentation was a pale or blue
      gray lesion associated with severe intravascular coagulation histologically
      involving the vessels in the lesion. In the three patients without signs of
      systemic toxicity, a swollen, erythematous skin lesion persisted for as long as
      one week; histologically, the intravascular coagulation within these lesions was
      mild. In clinicopathological terms, the entity in these six patients could be
      clearly classified as either fulminant or subacute. In the fulminant type,
      immediate surgical debridement of necrotic fascia is required; in the subacute
      type, incision and drainage alone are sufficient.

PMID- 9037920
TI  - Squamous cell carcinoma arising from lupus vulgaris on an old burn scar:
      diagnosis by polymerase chain reaction.
AB  - A 66-year-old Japanese woman with a squamous cell carcinoma (SCC) arising from
      lupus vulgaris (LV) on an old burn scar on the left lower extremity is described.
      Ziel-Neelsen stain of a direct smear from the surface exudate showed acid-fast
      bacilli. Repeated culture for tubercle bacilli was negative, probably due to a
      technical error. The diagnosis of LV was successfully made by polymerase chain
      reaction (PCR). LV and burn scar are common preceding diseases for SCC. The
      former is rare in the U.S., Europe, and Japan. We were unable to determine
      whether only one of the two conditions or a combination of both was the true
      predisposing factor responsible for the development of this SCC. However, this
      case may be the first report of SCC arising from coexistent LV and a burn scar in
      which the diagnosis was confirmed by PCR.

PMID- 9037921
TI  - Three cases of linear lichen planus caused by dental metal compounds.
AB  - Three cases of linear lichen planus on the lower extremities unaccompanied by
      mucous lesions are described. Dental metal compounds were thought to be the
      precipitating factor in all cases. Skin lesions did not respond to topical
      steroid ointment or antihistamines. Two cases showed a positive patch test
      reaction to gold (HAuCl4) and a positive lymphocyte stimulation test to gold
      compound (Gold sodium thiomalate). One case showed a positive patch test reaction
      to mercury (HgCl2), but a negative lymphocyte stimulation test. Suspected metal
      compounds were demonstrated in their dental materials. Removal of gold materials
      in one case gradually improved the lesions within 6 months with a transient
      erythematous swelling of the face shortly after removal of the metal. Both of
      these cases responded to oral disodium chromoglycate therapy. These results
      suggest that metal compound specific T cells might be responsible for the
      development of linear lichen planus.

PMID- 9037922
TI  - A case of localized pemphigus foliaceus.
AB  - Pemphigus foliaceus (PF) is most commonly observed on the face, scalp, chest and
      back at the onset of the condition. The case described here is that of an 81-year
      old female with a single PF lesion localized to the right cheek. A review of the
      literature published in English and Japanese disclosed only 3 cases of PF in
      which the patient presented with a single lesion, and 2 of these cases were
      referred to as "localized pemphigus foliaceus".

PMID- 9037923
TI  - Systemic scleroderma associated with Graves' disease.
AB  - We describe a case of systemic scleroderma associated with Graves' disease and
      review six previously described cases associating the two diseases. Our case
      seems to be unique in that Graves' disease preceded the occurrence of systemic
      scleroderma.

PMID- 9037925
TI  - Association of Melkersson-Rosenthal syndrome with rosacea.
AB  - A rare case of Melkersson-Rosenthal syndrome with all the cardinal signs of the
      triad, including facial swelling, facial nerve palsy and glossitis, is described.
      The additional feature of this case was an association with rosacea.

PMID- 9037924
TI  - A case of drug eruption due to simultaneous sensitization with three different
      kinds of drugs.
AB  - We reported a case of drug eruption induced by combined treatment with three
      different kinds of drugs, amoxapine, mexiletine hydrochloride and cefaclor. A 63
      year-old Japanese woman suffering from 11 years of standing reflex sympathetic
      dystrophy developed multiple erythematous papules on her trunk and extremities
      after taking 14 kinds of drugs. The provocation challenge produced positive
      reactions to amoxapine, mexiletine hydrochloride, and cefaclor, but was negative
      to the other drugs. We discussed the mechanism of simultaneous sensitization to
      three different kinds of drugs in our case.

PMID- 9037926
TI  - Persisters, relapse (reactivation), drug resistance and multidrug therapy (MDT):
      uniform diagnostic guidelines for leprosy are needed.

PMID- 9037927
TI  - Sarcoidosis associated with Basedow's disease.

PMID- 9037928
TI  - Evidence-based care. A new paradigm for clinical practice.

PMID- 9037929
TI  - The relationship of ambulation in labor to operative delivery.
AB  - An abbreviated version of the Nurse-Midwifery Clinical Data Set was used to
      gather data on all women (n = 3,049) who began intrapartum care with a nurse
      midwife in three sites. Demographic information, intrapartum care, and outcomes
      were recorded. The association of ambulation in labor with operative delivery was
      examined in a low-risk sample (n = 1,678) of women who did not receive care
      measures (epidural anesthesia, oxytocin induction or augmentation) that preclude
      mobility in labor. Women who ambulated for a significant amount of time during
      labor (compared with those who did not ambulate) had half the rate of operative
      delivery (2.7% vs. 5.5%).

PMID- 9037930
TI  - Transfer rates from freestanding birth centers. A comparison with the National
      Birth Center Study.
AB  - This article reviews retrospective data derived from Sharp The BirthPlace. San
      Diego for 1993-94 and from the University of California. Irvine, Birthing Center
      for 1994 and compares these findings to data obtained from the National Birth
      Center Study (NBCS). The focus of this article is on intrapartum transfer rates
      from the two freestanding birth centers as a critical clinical indicator. Cause
      specific transfer rates were calculated for eight clinical conditions. Data
      suggest that cause-specific intrapartum transfer rates are influenced by factors
      such as risk profile of the client population, distance to the referral center
      and mechanisms of transfer, definitions and diagnostic criteria used, and
      clinical practice guidelines. Reports from the literature, such as NBCS data,
      might serve as points of reference, but are likely not appropriate baseline
      indicators (benchmarks of "best practice") for clinical events, against which
      individual performance can be measured; rather, these benchmarks should be
      individually defined, based on characteristics unique to each birth center.

PMID- 9037931
TI  - Becoming a father. First-time fathers' experience of labor and delivery.
AB  - In this study, ethnographic interviews were used to identify first-time fathers'
      experiences of the birth of their first child. Fourteen fathers were interviewed,
      and prenatal expectations of the experience are compared with the fathers'
      perceptions after the birth. Although the fathers expected to be treated as part
      of a laboring couple, they found that they were relegated to a supporting role.
      Initially the fathers were confident of their ability to support their wives, but
      they found that labor was more work than they had anticipated. They became
      fearful of the outcome, but hid these fears from their partners. Later, they
      found that their focus moved from their wives to their babies at the time of
      birth. The men all completed the experience with an enhanced respect for their
      wives. Fathers should be included in labor management plans and need support for
      their role as coach, particularly when their wives experience pain. They also
      need to be encouraged to eat and take a break from their wives' labor when
      appropriate.

PMID- 9037932
TI  - A study of the beliefs and birthing practices of traditional midwives in rural
      Guatemala.
AB  - This is a descriptive study of the beliefs and practices of the traditional
      midwives in a rural Guatemalan village. During pregnancy and birth, traditional
      midwives who have received minimal or no training attend more than 80% of the
      indigenous Mayan women. Data were obtained from interviews with the midwives and
      from direct observation of midwives attending births. The midwives had few skills
      with which to handle complications. They failed to use basic aseptic technique
      and were unfamiliar with lifesaving skills such as fundal massage and proper
      infant stimulation. Even though most of the midwives interviewed had attended a
      Ministry of Health training course, they lacked basic knowledge of safe obstetric
      practices. To reduce infant and maternal mortality rates, traditional midwives
      must be adequately trained. The teaching methods used by an indigenous Guatemalan
      group training elderly, illiterate midwives are described as an example of an
      effective training program.

PMID- 9037933
TI  - Association between significant decrease in barometric pressure and onset of
      labor.
AB  - To determine whether there is any correlation between sudden decrease in
      barometric pressure and onset of labor, a non-experimental, retrospective study
      at a 948-bed tertiary care hospital was done. Pregnant patients of 36 weeks
      gestation or more who presented with spontaneous onset of labor during the 48
      hours surrounding the 12 occurrences of significant drop in barometric pressure
      in 1992 were included in the study. Significantly more occurrences of onset of
      labor were identified in the 24 hours after a drop in barometric pressure than
      were identified in the 24 hours prior to the drop in barometric pressure (P <
      0.05). Therefore, the overall number of labor onsets increased in the 24 hours
      following a significant drop in barometric pressure.

PMID- 9037934
TI  - Abrupt onset of severe pain at term. A case report.
AB  - This case report involves an adolescent primigravida at term who was admitted
      with urinary complaints to the labor and delivery unit of a medical center.
      Within an hour, she suddenly began screaming and complaining of severe pain
      running from her anterior pelvis through her vagina and up her spine. Three days
      of very challenging co-management of the patient, with several recurrences of
      acute pain, followed. Differential diagnoses that could explain this patient's
      symptoms are reviewed and discussed. Difficult management issues, including the
      stress of clinical management in the face of unidentified disease processes, are
      addressed. Lacking a certain diagnosis even retrospectively, the authors request
      comments from readers.

PMID- 9037935
TI  - Sculpting a nurse-midwifery philosophy. Ernestine Wiedenbach's influence.
AB  - An educational project used in a professional-issues course for student nurse
      midwives is described. The class project involved nurse-midwives portraying (in
      clay), and subsequently discussing, their individual practice philosophies.
      Background information on the importance of philosophy statements is provided.
      Included is the historic influence of a certified nurse-midwife foremother,
      Ernestine Wiedenbach, on the professional importance of articulating a guiding
      philosophy.

PMID- 9037936
TI  - The historical relationship of nurse-midwifery with medicine.
AB  - This historical review of the literature highlights the struggles that American
      nurse-midwifery has undergone in defining itself to the medical profession.
      Because nurse-midwifery came into existence in this country close on the heels of
      the demise of traditional midwifery, it had many prejudices to overcome. For many
      years, nurse-midwifery allied itself with nursing to gain power and acceptance
      from physicians. Now, however, there is a move toward independence as nurse
      midwives are more visible and the effectiveness and safety of their practice have
      been established.

PMID- 9037937
TI  - Principles for a successful professional life.
AB  - Principles for a successful professional life as set out in this article are
      those that have been developed by Dr. Ruth Lubic over the more than 40 years that
      she has been a nurse and nurse-midwife. Several emanate from her experience in
      questioning conventional medical wisdom concerning maternity care and in pressing
      forward with innovative services in spite of overt and often covert opposition.
      Dr. Lubic credits childbearing families with providing the strength that nurtured
      her professional progress.

PMID- 9037938
TI  - The mother-friendly childbirth initiative. The first consensus initiative of the
      Coalition for Improving Maternity Services.

PMID- 9037939
TI  - Development of an Academic Nurse-Midwifery Service Program.

PMID- 9037940
TI  - Defining terminology for improved breastfeeding research.

PMID- 9037941
TI  - Audible in utero sound caused by the ultrasonic radiation force from a real-time
      scanner.
AB  - While investigating in utero sound levels during vibro-acoustic stimulation on
      the maternal abdomen it was noticed that noise level increased when the real-time
      ultrasonic scanner beam was directed at the sensing hydrophone. The noise was
      recorded and later analysed for frequency content and waveform. It appeared
      related to the scanning and frame rate frequencies of the scanner used. Sounds
      may originate from radiation pressure produced when the ultrasound beam is
      absorbed by tissue or reflected from bone or the metal hydrophone. This implies
      that although ultrasound cannot be heard per se, any modulation of its intensity
      will produce vibrations in the maternal tissues or reflecting structures such as
      skull bone, and especially stapes, malleus and incus, that would be heard as
      sound by the fetus. The intensity of the sound produced varied with orientation
      of the transducer beam and this may itself produce a stimulation. Based on our
      recordings (Fig. 1), it was calculated (please see Appendix) that the fetus would
      hear a sound corresponding to 84dB noise pressure level in air.

PMID- 9037942
TI  - Vitamin D receptor in endometrial carcinoma and the differentiation-inducing
      effect of 1,25-dihydroxyvitamin D3 on endometrial carcinoma cell lines.
AB  - In view of the potential of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] as a cell
      differentiation-inducing agent in endometrial cancer, the localization of the
      vitamin D receptor (VDR) was examined immunohistochemically in 21 endometrial
      adenocarcinoma specimens, and the effect of 1,25(OH)2D3 on cell growth, as well
      as the phenotypic changes for cell maturation after treatment with 1,25(OH)2D3,
      was investigated in 2 endometrial carcinoma cell lines (AMEC-1, RL95-2). The VDR
      was detected in 14 of the 21 endometrial carcinoma specimens. The growth of RL95
      2 cells expressing VDR was inhibited to 44% when cultured with 50 nM 1,25(OH)2D3
      for 6 days. In contrast, the growth of AMEC-1 cells not expressing VDR was
      completely uninhibited even when cultured with 100 nM 1,25(OH)2D3 for 6 days. The
      RL95-2 cells exposed to 50 nM 1,25(OH)2D3 for 6 days had an increasing expression
      for 52.5 kD or 45 kD cytokeratin polypeptide, and they became columnar with
      pronounced polarity and formed gland-like structures when cultured in collagen
      gel. These results suggest that endometrial adenocarcinoma is a target for
      1,25(OH)2D3, which appears to function as a cell-differentiation-inducing agent
      for the treatment of endometrial cancer.

PMID- 9037943
TI  - Comparative cytogenetic studies of benign, borderline, and malignant epithelial
      ovarian tumors.
AB  - Comparative cytogenetic studies were performed in 40 cases of untreated
      epithelial ovarian tumors. Of these 40 tumors, 13 were classified as benign, 3 as
      borderline, and 24 as malignant, according to the WHO classification for ovarian
      tumors. Of 13 benign ovarian tumors, 4 (30.8%) showed chromosomal abnormalities.
      Of 4 ovarian tumors, 3 (75%) had single chromosomal abnormalities, and the
      remaining tumor (25%) retained multiple chromosomal abnormalities. Of 3
      borderline-malignant ovarian tumors, 2 (66.7%) showed chromosomal abnormalities.
      Of 2 ovarian tumors, 1 (50%) indicated single chromosomal abnormalities, and the
      remaining tumor (50%) revealed multiple chromosomal abnormalities. Of 24
      malignant ovarian tumors, 20 (83.3%) showed chromosomal abnormalities. Of these
      20 ovarian tumors, 3 (15%) had single chromosomal abnormalities, and the other 17
      (85%) exhibited multiple chromosomal abnormalities. These data indicate that the
      rate of chromosomal abnormalities, especially multiple abnormalities, increases
      following the progression of malignancy in epithelial ovarian tumors.

PMID- 9037944
TI  - Urinary levels of nitric oxide metabolites in normal pregnancy and preeclampsia.
AB  - OBJECTIVE: The purpose of this study is to clarify the physiological role of
      nitric oxide (NO) in normal pregnancy and preeclampsia. STUDY DESIGN: Thirty
      normotensive women (1st trimester, n = 7; 2nd trimester, n = 6; 3rd trimester, n
      = 10; puerperal period, n = 7) and 19 patients with preeclampsia (3rd trimester,
      n = 9; puerperal period, n = 10) were studied. Urinary and blood samples were
      obtained from each participant who was designed to be under the same condition.
      Urinary NOx (nitrate/nitrite) was measured with Greiss method after nitrate
      reduction. Urinary cyclic guanosine 3',5'-monophosphate (cGMP), creatinine
      clearance, serum triglyceride, uric acid, albumin and blood cell count were also
      determined. RESULTS: 1) Urinary NOx levels in 2nd and 3rd trimester of normal
      pregnancy tended to be higher than those in 1st trimester. There was also a
      tendency of decreased urinary NOx in puerperal period. Urinary NOx in antepartum
      preeclampsia was significantly lower than that of normal pregnancy in 3rd
      trimester. 2). Urinary cGMP was significantly higher in 2nd trimester of normal
      pregnancy than in 1st trimester. There was also a tendency of decreased urinary
      cGMP in puerperal period. In preeclampsia the values in 3rd trimester were
      significantly higher than those in puerperium. 3) A significant positive
      correlation was observed between urinary NOx and cGMP only in 3rd trimester of
      normal gestation. 4) In normal pregnancy of 3rd trimester, significant negative
      correlations were observed between urinary NOx and either of mean blood pressure
      or serum triglyceride. In preeclampsia of antepartum, urinary excretion of NOx
      was significantly correlated positively with creatinine clearance and negatively
      with mean blood pressure or serum uric acid. Urinary excretion of NOx in both of
      normal pregnant and preeclamptic women in 3rd trimester was significantly
      correlated with serum triglyceride. CONCLUSION: It is suggested that NO may
      modulate the cardiovascular changes during pregnancy and impaired production of
      the molecule may play a significant role in the pathophysiology of preeclampsia.

PMID- 9037945
TI  - Intravenous immunoglobulin as primary therapy or adjuvant therapy to intrauterine
      fetal blood transfusion: a new approach in the management of severe Rh
      immunization.
AB  - Maternal high dose intravenous immunoglobulin (IVIG) has shown promise in the
      management of severe Rh-immunization. Intravenous immunoglobulin, blocks Fe
      mediated antibody transport across the placenta and blocks destruction of fetal
      red cells and reduces maternal antibody levels. We have tried this new therapy in
      6 patients with severe Rh-immunization, with high maternal antibody titres and
      previous hydrops and intrauterine deaths. Intravenous immunoglobulin was given
      from 13-18 weeks of gestation 3-4 weekly, till intrauterine transfusion (IUT) or
      delivery. Intensive fetal monitoring was done. No fetal hydrops or deaths
      occurred in any of the 6 cases. Only 2 cases needed intrauterine transfusion.
      IVIG delayed the onset of fetal anemia by 8-17 weeks thus deferring the need for
      IUT. All pregnancies continued till 32-36 weeks and all 6 babies did well in the
      neonatal period.

PMID- 9037946
TI  - A study on fetal urinary tract anomaly: antenatal ultrasonographic diagnosis and
      postnatal follow-up.
AB  - OBJECTIVE: To evaluate the incidence, associated anomalies, and the type of
      congenital urinary tract anomaly and to know the cause of congenital
      hydronephrosis. METHODS: In 4.5 years, 5,442 fetuses had ultrasonography and 48
      cases of fetal urinary tract anomaly were detected. Ultrasonogram was done after
      delivery with further examination as necessary. RESULTS: The incidence of all
      types of anomaly was 4.3% (236/5,442) and the incidence of urinary tract anomaly
      was 0.9% (48/5,442, 8.8/1,000 births) of all babies born and 20.3% (48/236) of
      entire anomaly. Types of urinary tract anomaly were as follows; hydronephrosis
      (37 cases), multicystic dysplastic kidney (5 cases), polycystic kidney disease (2
      cases), renal agenesis (2 cases), ectopic kidney (1 case) and hypoplastic kidney
      (1 case). Associated anomalies were found in 8 cases (16.7%) among 48. Causes of
      hydronephrosis were ureteropelvic obstruction in 13 cases, ureterovesical
      obstruction in 4 cases, vesicoureteral reflux in 2 cases, proximal ureteral
      obstruction in 2 cases, and no specific causes in 16 cases. CONCLUSIONS:
      Antenatal ultrasonography is a very useful diagnostic tool in the detection of
      urinary tract anomaly and a careful search for other anomalies is indicated when
      urinary tract anomaly is found.

PMID- 9037947
TI  - A rapid serological detection method for squamous cell carcinoma.
AB  - OBJECTIVE: We conjugated the squamous cell carcinoma (CA)-associated antibody
      (anti-YM antibody) with gelatin particles. We found that these particles reacted
      specifically with the tumor-associated antigen (YM antigen) in serum samples from
      patients with squamous cell CA of the uterine cervix and various organs (GPA
      reaction). METHODS: 1) We performed immunohistochemical studies of the YM antigen
      in dysplasia and invasive squamous cell CA of the uterine cervix; 2) We measured
      the GPA reaction in various malignant and non-malignant gynecologic diseases.
      RESULTS: 1) Immunohistochemical localization of the YM antigen was over 75% in
      cases of dysplasia and invasive squamous cell CA of the uterine cervix, and was
      21% in normal squamous epithelium of the uterine cervix. 2) The GPA reaction in
      gynecologic diseases was positive in 57.1% of the dysplasia cases; in CIS cases,
      69.2%; in cervical CA, 83.0%; in corpus CA, 25.0%; in leiomyoma 16.7%; and in
      pregnant serum samples, 66.7%, 3) GPA reactions in non-ob-gyn cases were positive
      in 68.8% of the cases of squamous cell CA of the head and neck; 66.7% in cases of
      squamous cell CA of the lung; and 25.0% in adenoCA of the lungs whereas the sera
      of patients with benign tumors and of healthy persons were free of the YM
      antigen. CONCLUSION: We concluded that this newly developed GPA-reaction
      measurement is a simple and reliable serologic test for detecting the initial
      stage of squamous cell CA of various organs and for monitoring its postoperative
      status.

PMID- 9037948
TI  - Choriocarcinoma in infant and mother: a case report.
AB  - We present a case of gestational choriocarcinoma that developed in a pregnant
      woman with metastases to her baby. In this case, severe anemia and hepatomegaly
      of the baby were noticed after delivery. Despite intensive treatments, the tumor
      progressed rapidly, and the baby died at the age of 38 days. Accurate diagnosis
      was made after autopsy. When the baby's mother visited our hospital again at 4
      months postpartum, there were widespread multiple metastases to her lungs and
      liver. We want to emphasize that if a neonate or infant has anemia and/or
      hepatomegaly, it is necessary to be aware of the possibility of infantile
      choriocarcinoma with the presence of an occult tumor in the mother and to examine
      the mother's and infant's hCG levels immediately.

PMID- 9037949
TI  - Simultaneous intra- and extra-uterine pregnancy with ovarian hyperstimulation
      syndrome after induction of ovulation: a case report.
AB  - We present a case of polycystic ovary syndrome (PCOS) that developed simultaneous
      intra- and extra-uterine pregnancy with ovarian hyperstimulation syndrome (OHSS)
      after induction of ovulation with pure FSH-HCG. At 9 weeks of pregnancy, the
      bilateral tubal pregnancy caused an imminent spontaneous abortion, and both
      Fallopian tubes were resected. After the laparotomy, the pregnancy progressed
      without problems until 31 weeks and 5 days of pregnancy, when signs of
      spontaneous abortion appeared, and healthy twin female babies were delivered by
      cesarean section. The incidence of heterotopic pregnancy is increasing in cases
      in which inducers of ovulation or ART, such as IVF-ET and GIFT, have been
      employed. One must be well aware that the danger of heterotopic pregnancy
      following induction of ovulation is imminent, particularly in cases with risk
      factors of multiple and/or extra-uterine pregnancy, such as PCOS, a history of
      tubal restoration, and sexually transmitted disease(s).

PMID- 9037950
TI  - Sertoli Leydig cell tumor with malignant heterologous elements and raised alpha
      fetoprotein: a case report.
AB  - A case of a Sertoli Leydig cell tumor in a young female with virilizing symptoms
      and an androgenic endocrine profile with raised serum alpha-fetoprotein is
      presented. The tumor consisted predominantly of malignant epithelial and
      mesenchymal heterologous elements. Such a combination in the same tumor has to
      the best of our knowledge not been previously reported in English literature. The
      Leydig cells were immunohistochemically positive for alpha-fetoprotein. Sertoli
      Leydig cell tumors should be included in the differential diagnosis of tumors
      with raised alpha-fetoprotein. Chemotherapy in addition to surgery has been
      recommended for these tumors.

PMID- 9037951
TI  - A case of pregnancy with adult T-cell leukemia.
AB  - The incidence of adult T-cell leukemia (ATL) arising in women of childbearing age
      is documented infrequently. This report is the second in the world's literature
      of a case of ATL that occurred during pregnancy. A 43-year-old woman developed
      ATL during pregnancy and died of widespread disease 4 weeks after cesarean
      delivery.

PMID- 9037952
TI  - Psychiatric consultations in obstetric inpatients.
AB  - OBJECTIVE: The purpose of this study was to investigate the psychiatric
      consultation condition in the obstetric ward with particular attention paid to
      the reasons for referral, psychiatric diagnoses and recommendations. METHODS:
      This study was conducted in a medical center with 73 obstetric beds. All
      psychiatric consultations of obstetric inpatients during a 3-year period were
      included in this study. Data were derived from clinical charts and consultation
      records that included demographic data, reasons for referral, psychiatric
      diagnoses and treatment recommendations. RESULTS: Within the 3-year period, 28
      patients were referred for psychiatric consultation, or 0.3% of the 9,972
      obstetric admissions. The obstetric group represented 0.7% of all the psychiatric
      consultations. The most common reason for the referral was anxiety. Many
      obstetric problems, medical histories and psychiatric histories were found in
      these 28 patients. The most common diagnoses were depression or dysthymia, and
      schizophrenia. The diagnosis of organic mental disorders was rarely found. The
      vast majority of the psychiatric consultants were likely to recommend medication
      and psychological intervention. CONCLUSION: Even though there is a low
      psychiatric consultation rate among the obstetric inpatients, it does not mean
      that the prevalence rate of mental disorders is low in the obstetric patients.
      Psychiatric problems may be neglected or happen after patients are discharged.
      Organic mental disorders were rarely found in the obstetric patients which
      suggested a different pattern of mental disorders in the obstetric patients
      compared to other patients. The stress during child delivery needs further study
      for it may exacerbate or predispose a mental disorder. It is suggested that
      collaboration between obstetric staff and the consultation-liaison psychiatrists
      may provide better care for pregnant women patients.

PMID- 9037953
TI  - The role of HPV DNA testing in cervical neoplasia.

PMID- 9037954
TI  - Screening and epidemiological trends in cervical cancer.
AB  - The developed or less developed countries where basic conditions for the
      screening of cervical cancer are quite different in terms of essential factors
      such as accuracy of cytology, cost effectiveness and development of new methods
      of diagnosis. Considering these factors the screening program made by annual Pap
      smear with adjunctive cervicography and HPV DNA test in the women aged from 20 to
      69 years may have universal validity.

PMID- 9037955
TI  - Hybrid Capture method for detection of human papillomavirus DNA in clinical
      specimens: a tool for clinical management of equivocal Pap smears and for
      population screening.
AB  - High- and intermediate-risk types of human papillomavirus (HPV) in concert with
      cofactors are responsible for over 90% of cervical cancers world-wide. While the
      Pap smear is a valuable cancer prevention tool, its subjective nature leaves it
      error prone. As a result, HPV DNA testing appears to be a needed adjunct to the
      Pap smear. Hybrid Capture is a simple DNA test with high specificity and
      sensitivity which appears useful for clinical management of equivocal Pap tests
      and shows promise for mass screening.

PMID- 9037957
TI  - Interdisciplinary practice and education.

PMID- 9037958
TI  - The child's eye: memories of growing up with cystic fibrosis.
AB  - This qualitative study used a grounded theory approach to explore adolescent
      conceptualizations of their chronic illness experience and related life events. A
      purposive sample of 20 adolescents (12-18 years of age) with cystic fibrosis were
      interviewed. Adolescents used three protective strategies for reducing a sense of
      difference from peers: (1) keeping secrets, (2) hiding visible differences, and
      (3) discovering a new baseline. "Good friends" were a critical source of support
      and decreased the importance of differences in their social world. Interventions
      should focus on strategies for dealing with difficult peer situations and the
      negative reactions of others.

PMID- 9037959
TI  - African American teen mothers' perceptions of parenting.
AB  - The purpose of this study was to describe the childbearing African American
      teens' perceptions of parenting based on their own experiences. Focus group
      discussions were held with 17 teens in their school setting for 50 minutes each
      week. Group discussions were audiotaped, tapes were transcribed, and then
      analyzed for common themes. The unmarried teens ranged in age from 15 to 18
      years. Findings indicated that the teens depended on grandmothers to provide
      child care and for information about parenting. The teens identified parenting
      problems including crying, discipline, and conflicts dealing with grandmothers
      and the child's father. Teens wanted more information about breastfeeding and
      minor childhood diseases. The researchers identified that teens lacked
      information about their children's growth and development and safety issues.
      Findings have implications for nurses who care for childbearing teens and their
      children; and those involved in planning and implementing parent education
      programs for African American teen mothers and their families. Further research
      is indicated with larger samples of African American teens; and to explore the
      context of family relationships in which teen mothers and grandmothers share
      parenting for the teens' children.

PMID- 9037960
TI  - Fostering children's resilience.
AB  - Resilience is relevant to nurses because of its implications for health. Research
      on the resilience of children and adolescents has proliferated over the past five
      years. However, the specific processes underlying resilience and outcome
      variables require further study. Furthermore, few intervention studies have been
      conducted. This article describes resilience and factors that influence
      resilience of children, examines the relationship between resilience and health,
      identifies interventions that foster children's resilience and health, reviews
      research focusing on children's resilience, and suggests the relevance of
      resilience to nursing of children.

PMID- 9037961
TI  - Modes of thought, feeling, and action in infant pain assessment by pediatric
      nurses.
AB  - The components of the assessment process are identified and compared from an
      ethnography of the methods used by 65 pediatric nurses to assess the level of
      pain in a sample of infants younger than 1 year of age. Nine different modes of
      thought, feeling, and action were referenced in reaching judgments about pain
      levels. The five predominant modes were: deductive, clinical, inductive, testing,
      and knowing the infant. Over time, the participants had developed a preference
      for particular combinations of the elements which constitute these modes:
      repeated use of these preferred assessment methods gave more experienced
      pediatric nurses distinctive styles of pain assessment. Nurses demonstrated a
      wider "repertoire" of knowledge about how to assess pain than they customarily
      used: the selection of particular repertoire items varied by nurses' initial
      estimates, experience level, and personal assessment style. Findings support the
      proposition that an understanding of the infant pain assessment process must
      include nurses' selection and customary use of knowledge and data available to
      them, as well as the intrinsic nature of that information.

PMID- 9037962
TI  - Sibling abuse: another component of domestic violence.
AB  - As the issue of domestic violence is explored, components of the problem emerge.
      Sibling abuse as one component of domestic violence is described in this case
      study. The incidence, risk factors, and nursing care for sibling abuse are
      discussed. Nursing care for sibling abuse occurs in both the hospital and the
      community setting. The majority of care must occur in the community health
      setting because of shortened hospital stays. A review of the literature
      highlights a lack of research despite an indication of the potential magnitude of
      the problem. Further research in this area of domestic violence is needed.

PMID- 9037963
TI  - Welfare reform: will it break the cycle of dependency?

PMID- 9037964
TI  - Today's challenge of change.

PMID- 9037965
TI  - Childhood injury: significance and prevention strategies.

PMID- 9037966
TI  - Patients first and always.

PMID- 9037967
TI  - Controlling caries.

PMID- 9037968
TI  - Teens, calcium and osteoporosis.

PMID- 9037969
TI  - Trends in dental care among insured Americans: 1980 to 1995.
AB  - This article presents data on the use of a wide range of dental services by
      insured patients between 1980 and 1995. The patterns of dental care revealed in
      this study show clear trends that indicate profound improvements in oral health.
      These improvements are evident in all age groups, and the effect of the caries
      decline in children that began about 20 years ago has moved well into the adult
      population. As those born since about 1950 continue to age and represent an ever
      increasing proportion of the population, the overall need for restorative care of
      all types will continue to diminish.

PMID- 9037970
TI  - Commentary: a proud achievement for American dentistry.

PMID- 9037971
TI  - Comparing the accuracy of reversible hydrocolloid and elastomeric impression
      materials.
AB  - This in vitro investigation evaluated the accuracy of reversible hydrocolloid,
      vinyl polysiloxane and polyether elastic impression materials used in conjunction
      with two die stones. The authors made impressions in an experimental environment
      that approximated clinical conditions in regard to temperature and moisture.
      Analysis of variance and t-tests were used to compare corresponding measurements
      on experimental casts made from the various impression materials.

PMID- 9037972
TI  - Off-site dental evaluation program for prospective bone marrow transplant
      recipients.
AB  - The authors evaluated the usefulness of an off-site dental evaluation program for
      bone marrow recipients. This evaluation packet enabled patients scheduled for
      bone marrow transplants to be evaluated by, and receive any treatment from, their
      own dentist rather than a dentist at the transplant center. The program generally
      was effective in achieving its goals and was well-accepted by patients and
      dentists alike.

PMID- 9037974
TI  - Using fenestration technique to treat a large dentigerous cyst.
AB  - Dentigerous cysts are commonly encountered in the practice of dentistry and oral
      and maxillofacial surgery. Treatment modalities range from enucleation to
      marsupialization, and are based on the premise that the pathological process can
      be controlled locally with minimal injury to the adjacent host structures. In a
      child, however, loss of permanent tooth buds in the management of a large
      dentigerous cyst can be devastating. This article describes the technique of
      fenestration, which removes this entity and preserves the developing dentition.

PMID- 9037973
TI  - The effect of resin desensitizing agents on crown retention.
AB  - Many dentists use resin primers and adhesives to prevent post-cementation
      sensitivity of teeth restored with crowns. However, little information is
      available regarding the effect of these resins on crown retention. This
      laboratory study concluded that two popular resins, Gluma Desensitizer (Heraeus
      Kulzer) and One-Step (Bisco Dental Products), had little or no effect on the
      retention of crowns luted with zinc phosphate, glass ionomer or resin-modified
      glass ionomer cements.

PMID- 9037975
TI  - Chronic lymphocytic leukemia of B-cell origin: oral manifestations and dental
      treatment planning.
AB  - Chronic lymphocytic leukemia, or CLL, is the most common form of leukemia in the
      Western Hemisphere, accounting for approximately 30 percent of all cases. With
      patients having an expected life span of more than seven years, CLL is a
      relatively indolent hematologic malignant disease that, while incurable, often
      has a prognosis compatible with relatively normal dental treatment planning. The
      authors present four case reports of CLL in a dental setting, as well as an
      update on the diagnosis, prognosis and dental treatment of patients with CLL of B
      lymphocyte origin.

PMID- 9037976
TI  - Educating Americans about dental care benefits.
AB  - Freedom of choice is the fundamental premise on which American dentistry has
      achieved its enviable position of providing good oral care, at a moderate cost to
      a majority of the American people who choose to see a dentist regularly. As
      dentists, it is our responsibility that they receive the level and quality of
      care to which they are entitled. It is our responsibility to preserve optimum
      oral care for our country. Educate your patients and their employers.

PMID- 9037977
TI  - Office-based training in tobacco cessation for dental professionals.
AB  - During a 90-minute, on-site training session, a dentist/tobacco-cessation
      educator trained 293 dental professionals from 57 offices. The authors report
      statistically significant increases between the pre-training and follow-up
      surveys for 12 tobacco-cessation activities and the amount of time spent on such
      activities (P < .001). Using participants' estimates-taken at three months after
      the training-the authors calculated that an average of two patients per office
      had stopped using tobacco, two had stopped and relapsed, and eight patients were
      considering stopping tobacco usage.

PMID- 9037978
TI  - A simple, inexpensive home dental care aid.

PMID- 9037979
TI  - Fabricating light-cured provisional restorations.

PMID- 9037980
TI  - To solo or not to solo.
AB  - An analyst from the ADA Survey Center provides a brief overview of the
      differences and similarities of solo and nonsolo (group) practices, based on data
      gathered from the 1995 Survey of Dental Practice.

PMID- 9037981
TI  - Unions in dentistry.

PMID- 9037982
TI  - Charles Darwin and the foundations of clinical genetics in dentistry.

PMID- 9037983
TI  - Defining primary care.

PMID- 9037984
TI  - Careful considerations regarding EMMs.

PMID- 9037985
TI  - Refractive surgery.

PMID- 9037986
TI  - Pharmacologic management of cytomegalovirus retinitis: review of current and
      future therapeutic modalities.
AB  - BACKGROUND: A number of new medications and modes of drug delivery have been
      introduced for the management of cytomegalovirus (CMV) retinitis in AIDS
      patients. New modes of treatment have attempted to prolong intervals between
      dosing and reduce drug-related toxicity in an effort to improve quality of life.
      METHODS: The ophthalmic, infectious disease, and pharmacologic literature were
      reviewed and evaluated for trends and new approaches to the management of CMV
      retinitis. RESULTS: Ganciclovir and foscarnet have been the mainstays in
      management of CMV retinitis. Intravenous administration of these drugs is costly,
      time-consuming, and complicated by numerous toxicities. Changes in the delivery
      of anti-viral drugs have involved intravitreal injections and implant devices.
      Other new methods involve liposomal systems to increase drug contact time, use of
      longer-acting drugs with less-frequent dosing requirements, and methods to
      improve quality of life by avoiding intravenous drug delivery. CONCLUSIONS: A
      number of strategies have evolved to manage cytomegalovirus retinitis. Patients
      are living longer with AIDS. With increased survival comes increased risk of CMV
      retinitis and the need for more-effective treatments to preserve retinal
      integrity. The optometrist must become aware of the potential of these drugs to
      control retinitis, protect functional vision, and maintain quality of life.

PMID- 9037987
TI  - Analysis of methods for predicting near-magnification power.
AB  - BACKGROUND: Data were analyzed from 25 consecutive patient visits to the Low
      Vision Rehabilitation Service at Southern College of Optometry, during which
      magnification for near was recommended. METHODS: Linear regressions with analysis
      of variances were calculated for the results obtained from four near-different
      near-magnification prediction-calculation methods to determine how accurately
      they predicted the final near recommended magnifications. A t-test was performed
      to look for mean differences between calculation methods. RESULTS: No
      significance was found between the means of three of the calculation methods; a
      significant difference was found for one. However, all four near-magnification
      calculation methods significantly predicted final near magnification.
      CONCLUSIONS: Low-vision rehabilitation clinicians may feel comfortable using any
      of the four near-magnification methods Choice of method may be a reflection of
      previous method usage by the clinician. Use of the Lighthouse Near Acuity Test
      Chart reduces the need to calculate the near-magnification power with which to
      begin near-magnification testing.

PMID- 9037988
TI  - Swelling of collagen intracanalicular implants.
AB  - BACKGROUND: Absorbable intracanalicular collagen implants are used to attempt to
      determine if permanent closure of the tear drainage system will diminish or
      alleviate the signs and symptoms of dryness. The rate of swelling of the collagen
      implants was measured in vitro in this study. METHODS: Collagen implants were
      submersed in saline, Refresh Plus artificial tears or Tobrex antibiotic solution
      on a hanging drop microscope slide. The diameter of the collagen rod was measured
      over time using videotaping and image processing. RESULTS: The 0.3- and 0.4-mm
      diameter collagen implants swelled approximately 55% to 65% in Unisol 4
      Preservative Free saline and Refresh Plus artificial tear solution, with the
      majority of the swelling occurring over the first 30 minutes. The 0.4-mm diameter
      implants took slightly longer to reach the fully swollen state than did the 0.3
      mm implants. They swelled somewhat less in Tobrex Ophthalmic Solution.
      CONCLUSIONS: Collagen implants swell approximately 60%, with the majority of the
      swelling occurring in the first 30 minutes. Thus, it will take approximately 30
      minutes after insertion of the implants for the full occlusive effect to occur.

PMID- 9037990
TI  - Corneal wrinkling in a hydrogel contact lens wearer with Marfan syndrome.
AB  - BACKGROUND: Corneal distortion in contact lens wear can be produced by epithelial
      wrinkles, compression rings, and anterior corneal surface mosaic. True corneal
      wrinkling can also occur but is an extremely rare phenomenon. These conditions
      can be manifested as alterations in keratometry and corneal topography. METHODS:
      A case report is presented of a 17-year-old patient with Marfan syndrome. Central
      corneal wrinkling developed in his right eye while he was wearing low-water
      content hydrogel contact lenses. No visual discomfort or distortions were noted.
      RESULTS: The patient was refitted with a non-HEMA hydrogel polymer contact lens,
      with no further episodes of corneal wrinkling observed during subsequent care of
      the patient. CONCLUSIONS: This case represents an example of corneal wrinkling in
      a patient wearing hydrogel contact lenses. It is unlikely this finding is related
      to Marfan syndrome.

PMID- 9037989
TI  - Association between visual reaction time and batting, fielding, and earned run
      averages among players of the Southern Baseball League.
AB  - BACKGROUND: This study was performed to investigate the relationship between
      vision reaction time (VRT) and batting, fielding, and pitching skill in baseball.
      METHODS: A vision screening of 213 professional baseball players in the Southern
      Baseball League was performed, and the visual reaction times of these players
      were determined. Official Southern Baseball League statistics were consulted to
      obtain the players' batting average, fielding average, and earned run average.
      RESULTS: The mean visual reaction time for all players was 239 msec. There was no
      significant association between mean VRT and age or race. The mean VRT for
      dominant eyes was not significantly different from the mean VRT for nondominant
      eyes. For the 92 players who batted at least 100 times, an association was found
      between mean VRT and batting average (p = 0.017). For the 168 fielders in the
      league playing at least 20 games, no statistically significant association was
      found between mean VRT and fielding average. Similarly, no association was found
      between mean VRT and earned run average for the B8 pitchers who had participated
      in more than 20 games. CONCLUSIONS: An association was found between visual
      reaction time and batting skill in baseball. No association was found between
      visual reaction time and fielding or pitching skill.

PMID- 9037991
TI  - Asymptomatic posterior orbital cellulitis resulting from ethmoid/maxillary
      sinusitis.
AB  - BACKGROUND: Although vision-threatening sinusitis complications are not uncommon,
      an unusual case of asymptomatic posterior orbital cellulitis resulting from
      maxillary and ethmoidal sinus infection is presented. METHODS, RESULTS: An 11
      year-old girl was brought to us for a routine optometric examination, reporting
      only blurred distance vision. A mild afferent pupillary defect was the key to
      detection and diagnosis of a vision-threatening posterior orbital cellulitis.
      CONCLUSIONS: A literature review of relevant anatomic and pathologic mechanisms,
      as well as radiologic recommendations, follows. This case appears to be a new
      clinical entity, an asymptomatic variant of posterior orbital cellulitis.

PMID- 9037992
TI  - Pharmacist compounding of analgesic medication: the risk of a little-known
      practice.

PMID- 9037993
TI  - Pain after injury: some basic mechanisms.

PMID- 9037994
TI  - Initial evaluation of headache.

PMID- 9037995
TI  - Evaluation and treatment of low back pain.

PMID- 9037996
TI  - Pain management for labor and delivery in the 90s.
AB  - Although variable, labor pain is among the most severe of pain syndromes, and has
      been described as severe to excruciating in 50 to 70 percent of primiparas.
      "Twilight sleep" or amnesia was commonly used in the first half of this century
      via potent intramuscular, intravenous and inhalational agents. Subsequently,
      epidural anesthesia, first caudal then lumbar was used which offered superior
      pain relief without clouding the sensorium. However, epidurals with local
      anesthetics also contributed to dense sensory and motor blocks which are not
      necessary for labor. Presently, both spinal and epidural opioids are used along
      with decreasing doses of local anesthetics, rendering the laboring patient a
      relatively pain-free labor but allowing her more mobility and control of her
      environment.

PMID- 9037997
TI  - Pediatric pain management.
AB  - It is now recognized that from the newborn period onwards, children are capable
      of experiencing pain. This includes the premature infant. The challenge for
      healthcare providers is to incorporate methods of pain assessment and treatment
      into their daily practices. The child's understanding of pain closely follows the
      cognitive and behavioral model developed by Jean Piaget. Based on these
      developmental stages, pain assessment measures have been developed. Pharmacologic
      advances have accompanied this improved understanding of infant, child, and
      adolescent psychology. While acute pain accounts for the majority of children's
      experiences, recurrent/chronic pain states do occur (e.g. sickle cell related and
      neuropathic) and can be effectively treated.

PMID- 9037998
TI  - Types of pain treatment facilities referral selection criteria: are they
      medically and cost effective?

PMID- 9037999
TI  - Utilizing the clinical nurse specialist to promote interdisciplinary pain
      management.

PMID- 9038000
TI  - The golden rule.

PMID- 9038001
TI  - Apoptosis (programmed cell death) of transitional ameloblasts and MHC class II
      expression in rat incisors.

PMID- 9038002
TI  - [The role of tau in neural morphogenesis].

PMID- 9038003
TI  - [Caveola--an old but new organelle].

PMID- 9038004
TI  - [Antigen retrieval: its significance and drawbacks in immunohistochemistry].
AB  - One of the biggest problems in immunohistochemistry has been how to maintain both
      good morphology and the immunoreactivity of antigens in tissue sections. Various
      techniques to retrieve the immunoreactivities of antigens (unmasking) after
      routine tissue preparations, such as fixation, dehydration and embedding, have
      been devised and are now finding their way into use for immunostainings in not
      only cytohistological investigations but also pathoclinical diagnoses. In this
      report, first, the mechanisms and significance of both fixation and antigen
      retrieval were surveyed from the viewpoint of protein inactivation. Second, some
      practical problems and notes in two of the most popular unmasking techniques,
      enzyme digestion and heat-induced epitope retrieval (HIER), were reviewed in
      order to adapt the techniques precisely in immunohistochemistry. The major
      artifact induced by fixation is the masking of tissue antigens due to cross
      linking among the amino-acid residues of proteins. It is important to choose a
      proper fixing condition for each antigen considering its biochemical nature and
      resistance to the fixation. (Table 2), and to keep the fixing conditions to a
      minimum so that the immunoreactivity of the antigen can be readily retrieved by
      various unmasking techniques (Table 3, Fig. 1). Antigen retrieval per se is the
      process causing protein denaturation in tissues, just like many other protein
      inactivation processes (Table 1). Enzyme digestion may etch the masking parts of
      proteins around an antigen to expose its epitope. Although enzyme digestion is
      relatively simple and its treatment condition easy to control, the results are
      not necessarily dramatic and consistent depending on the types or lots of
      enzymes. Thus, one must find his/her own digestion manual to achieve the best
      staining result for each antigen (e.g., Table 4). For example, pepsin digestion
      gave the best results in the immunostaining of bromo-deoxyuridine (BrdU) and
      proliferating cell nuclear antigen (PCNA), whereas other enzymes had little
      effect (Table 5). Heating may also cleave the polypeptide backbone and disrupt
      the cross-links produced by fixation. The heating effect on antigen retrieval is
      temperature-dependent and seems to be proportional to the product of temperature
      and time. In the case of PCNA immunostaining on paraformaldehyde-fixed paraffin
      embedded sections, heating at 90 degrees C for at least 3 min was required,
      however, as the heating condition became more severe, non-specific background
      stains also increased (Table 6), which is one of the most serious problems in
      antigen retrieval (Fig. 2a, c). One possible choice for avoiding such undesirable
      results is the combination of suboptimal heating (at 80 degrees C for 10-15 min)
      and pepsin digestion (Fig. 2b, d). An important theoretical consideration for
      employing such a dramatic method of denaturation is whether the masked antigen
      epitopes can be adequately exposed without giving rise to false-positive (or
      false-negative) results with previously trusted antibodies. It seems that each
      antigen requires a "tailor-made" tissue preparation for optimal preservation of
      its antigenicity and precise localization. In accordance with the development of
      immunology, molecular biology, genetics or embryology, the need for multiple
      immunostaining in combination with other technologies like in situ hybridization
      should increase in order to analyze the spatial and functional relationships
      among various molecules in situ. Antigen retrieval would then become a powerful
      strategy.

PMID- 9038005
TI  - The centenary of the problem of the interstitial cells of Cajal.
AB  - The intestinal pacemaker cells are often confused with the interstitial cells of
      Cajal. However, under this term, at least three kinds of histological structures
      have been discussed: 1) fibroblasts, 2) fibroblast-like cells consisting of
      several subclasses, and 3) specialized smooth muscle cells. To our surprise,
      Cajal (1889, 1893) described a chimeric composition of glial (Schwann) cells and
      varicose nerve terminals as interstitial (nerve) cells. Cajal could not explain
      the net work formation of the autonomic periphery by the neuron doctrine.
      Therefore, he described it as special neuron system. We studied a unique smooth
      muscle tissue that produces regular mechanical contractions of 10-12 cycles/min
      at the mesenteric border of the pacemaker area in the guinea-pig colonic flexure
      region. Based on the results of our studies, we reevaluated both Cajal's original
      description and the cellular identity of intestinal pacemakers.

PMID- 9038007
TI  - Double gallbladder of swine.
AB  - In research on the reduplication of the pig gallbladder, a total of 297,531 swine
      from 130 breeders were surveyed at a slaughter house (Ozu Health Center, Ehime
      Prefecture, Japan) between October 1993 and December 1995. The swine were 6-7
      months old and their body weights ranged from 95 to 120 kg. Twenty-nine swine
      were found to have reduplication of the gallbladder. Of these 19 were females,
      nine were males and the sex of one was not identified. The second sac was smaller
      than main one. Eleven cases were diverticulum of a cystic duct (Type I).
      Diverticulum of the neck of the main gallbladder of six cases also gave rise to
      the second gallbladder (Type II). A sac attached to the neck of the main
      gallbladder via a small cystic duct in seven cases was another type of
      reduplication (Type III). Connection of the second sac to the middle of the
      hepatic duct via a small cystic duct was seen in three cases (Type IV). The
      positions of these small sacs to the main gallbladder were right (13 cases), left
      (II cases) and ventral (three cases). The fundus of one gallbladder were divided
      and resulted in double sacs (Type V). One second sac was set apart from the main
      gallbladder and attached to a hepatic duct of lateral left lobe of the liver
      (Type VI). One specimen of the Type III gallbladder had two additional small sacs
      as diverticulum of the cystic duct. Compared to occurrences in humans and the
      Japanese monkey, the ratio of gallbladder reduplication to normal system anatomy
      in swine was extremely low. It was similar to the ratio of spleen reduplication
      in swine (1/10,000).

PMID- 9038006
TI  - [Variations of the constrictor pharyngeal muscles in humans].
AB  - Fifteen halves of ten nonrandomized human cadavers were dissected under a
      stereoscopic microscope in order to examine the existence of variations in the
      constrictor pharyngeal muscles. Obvious variations of the constrictor muscles
      were found in three cases. The results are summarized as follows: 1. In the first
      case of variations, the superior constrictors arose from the pterygomandibular
      raphe and merged into the outer surfaces of the middle and inferior constrictors.
      This muscle was supplied by the upper part of the pharyngeal branches of the
      vagus. 2. In the second case, the muscle bundle of inferior constrictors
      originated from the thyroid cartilage and passed upward, joining the muscular
      fibers of the outer surface of the superior constrictors arising from the
      pterygomandibular raphe. Some of these muscular fibers extended to the surface of
      the posterior part of the pharyngobasilar fascia. This muscle was innervated by
      the lower part of the pharyngeal branches of the vagus. 3. In the third case, the
      lower part of the superior constrictors passed laterally between the
      stylopharyngeus and the glossopharyngeal nerve, running between the external and
      internal carotids in the retrostyloid space and reaching the cervical fascia
      around the submandibular triangle. This anomalous muscular bundle of superior
      constrictors was innervated by the carotid branch of the glossopharyngeal nerve
      and the middle part of the pharyngeal branches of the vagus.

PMID- 9038008
TI  - Distribution of vagal preganglionic neurons in the rat brain innervating thoracic
      and abdominal organs revealed by retrograde DiI tracing.
AB  - To investigate the distribution and number of preganglionic neurons which
      regulate motility and secretion in thoracic and abdominal organs in the vagal
      parasympathetic nervous system, the neuronal tracer DiI was injected into the
      organs and the distribution of retrogradely labeled neurons was examined in the
      rat brainstem. The stomach received the vast majority of efferent projections
      from the dorsal motor nucleus of the vagus nerve (DMV). The cecum and the
      duodenum also received projections from the DMV, but they originated from a
      smaller number of preganglionic neurons. Preganglionic neurons projecting to the
      stomach occupied the middle part of the DMV, those projecting to the cecum
      occupied the lateral part of the DMV, and those projecting to the duodenum were
      found in the medial edge of the DMV. The ventral and dorsal sides of the stomach
      wall were innervated by the left and right vagus nerves, respectively. However,
      immediately after passing the boundary between the stomach and duodenum, the left
      and right vagal nerve fibers mixed in the ventral and dorsal walls of the distal
      gastrointestinal tract. The nucleus ambiguous is a mixture of parasympathetic
      preganglionic neurons and motoneurons. In this study, we revealed that the major
      targets of these preganglionic neurons were the lungs and other thoracic organs.

PMID- 9038009
TI  - [The clinical study of clarithromycin for pulmonary Mycobacterium avium
      intracellulare complex infection].
AB  - A nationwide study was conducted to investigate the efficacy of Clarithromycin
      (CAM) on pulmonary atypical mycobacteriosis caused by the Mycobacterium avium
      Mycobacterium intracellulare complex, including intractable cases. Out of total
      97 patients examined, the analysis for bacteriological efficacy was possible in
      69 cases. The negative conversion of bacilli was observed in 18 cases (26.1%),
      and 5 out of 12 cases in which the follow-up was conducted turned out continued
      negative status. The efficacy of CAM was relatively high in the following cases:
      the duration of the disease was less than 6 months the extent of pulmonary
      lesions on chest roentogenograms was limited or moderate; and antituberculous
      agents which were previously unused were applied in combination with CAM. Also,
      the efficacy was high in cases where the dose of CAM was 600 mg/day or higher.
      Major side effect was mill to moderate digestive symptoms. In conclusion, at
      daily dose of 600 mg or higher, CAM was effective in the elimination or reduction
      of M avium M. intracellulare complex that caused atypical mycobacteriosis,
      without developing serious side effect. Treatment with this drug should be
      attempted in intractable cases.

PMID- 9038010
TI  - [The combination of amoxicillin-clavulanic acid and ofloxacin in the treatment of
      multidrug-resistant Mycobacterium tuberculosis].
AB  - A 67-year-old [correction of 53] man with multidrug resistant tuberculosis (MDR
      TB) had been persistently positive for acid-fast bacilli (AFB) both on sputum
      smear and also on culture with the Ogawa egg medium for 30 years since 1951. The
      case had been treated previously with isoniazid, rifampin, streptomycin,
      ethambutol, kanamycin, ethionamide, paraaminosalicylate and cycloserine; however,
      M. tuberculosis strains isolated from this patient acquired a high resistance to
      all of these agents. Then, a new regimen of chemotherapy, INH combined with
      ofloxacin (OFLX) and amoxicillin-clavulanic acid (AMPC/ CVA), was applied to the
      case. He was successfully treated with this regimen, and a marked decrease in the
      amount of AFB on smear as well as on culture was observed during the course of
      chemotherapy. No adverse effects were seen meanwhile. These data suggest that it
      is worth while to try a regimen containing AMPC/CVA and OFLX in the treatment of
      MDR-TB.

PMID- 9038011
TI  - [2 cases of lung disease caused by Mycobacterium avium complex occurred in middle
      aged women without underlying disorders, which we observed for more than 30
      years].
AB  - We reported 2 cases of Mycobacterium avium complex lung disease occurred in
      middle-aged women without underlying disorders, which we could observe for more
      than 30 years. One case was a 42-year-old woman started with bloody sputum, and
      the other was a 43-year-old woman with cough and sputum. In both cases, chest X
      ray films were normal on their first visit. More than 15 years after their first
      visit, Mycobacterium avium complex was isolated from their sputum or bronchial
      washing. During the observation, a cluster of small nodules in the periphery of
      the lung and bronchiectasis appeared and deteriorated, and excretion of the
      bacilli increased gradually. Their past history and family history were normal.
      Since lung disease caused by Mycobacterium avium complex progresses very slowly,
      long-time observation would be necessary to consider its pathogenesis.

PMID- 9038013
TI  - [Surgically unsuccessful cases with pulmonary tuberculosis].
AB  - Because of the development of effective drugs, surgical treatment for pulmonary
      tuberculosis has decreased in recent years, but there are some cases which
      require surgical operation in patients with drug resistant tuberculosis. Between
      1979 and 1994, 52 patients with pulmonary tuberculosis underwent surgical
      operations for the negative conversion of drug resistant bacilli. Pulmonary
      resection was the principal procedure and when a patient was not tolerant to this
      procedure, thoracoplasty or cavernostomy was selected. Continuation of bacilli
      positive sputum after the operation was seen in 12 cases (23.1%). The main causes
      of the failure were multiple drug resistance and remaining lesions. The
      unsuccessful rate in the patients with bacilli completely resistant to all of the
      5 main drugs (SM, KM, INH, RFP, EB) was extremely high amounting to 57.1%. When 2
      or more of the 5 main drugs were effective, the unsuccessful rate was 11.1%. A
      total of 21 cases had tuberculous lesions remaining in the lung postoperatively,
      because of bilateral lesions or poor lung function. In such cases, the
      unsuccessful rate was 42.3%. In the 31 cases that had no remaining lesion, the
      rate was 9.7%. There was no unsuccessful case in the patients who had 2 or more
      effective drugs and no remaining lesion. We reoperated on 6 patients and 5 of
      them got negative conversion. In the 2 of other patients who didn't undergo
      reoperation, their sputum became negative after long term postoperative
      chemotherapy, and the other 2 patients had only a few bacilli in ther sputum
      postoperatively. Nine cases were able to return to normal daily life.

PMID- 9038012
TI  - [Surgical treatment of multidrug resistant pulmonary tuberculosis cases].
AB  - We report on the results of surgical treatment of pulmonary tuberculosis cases
      intractable to ordinary therapy due to acquired drug-resistance against multiple
      anti-tuberculosis drugs (MDR-Tbc). MATERIAL AND METHOD: From 1983 to 1994, 54
      patients were administered surgical treatments (60 interventions in all) for
      pulmonary tuberculosis. Among them, 46 were MDR Tbc cases (52 interventions in
      all) and were enrolled for this study. The Japanese criteria for drug resistance
      were referred to, the threshold of resistance in each drug being as follows, INH
      0.1, RFP 50, EB 2.5, SM 20, KM 100, TH 25, EVM 100, CPM 100, CS 40, PAS 1
      microgram/ml. Bacteriological examinations of sputa were repeated in the
      postoperative period until upto several years, and the continued absence of Tbc.
      bacilli for more than 12 months was considered as cured. RESULTS: (1) 37 patients
      underwent removal of lung mass including tuberculous foci mainly fibrous cavitary
      lesions (40 interventions in all). The procedures are as follows 22 upper
      lobectomies and/or partial resections of adjacent lobes. 1 middle lobectomy. A
      lower lobectomy, 14 pneumonectomies, 2 segmentectomies. In 3 cases, multiple
      operations were carried out on 2 occasions; 2 upper lobectomies followed by
      completion pneumonectomies. 1 right upper lobectomy followed by left S3
      segmentectomy. Except 2 cases having died of pneumonia and suicide within 12
      months after operation, we have 38 cases available for evaluation.
      Bacteriological relapses were confirmed in 7 among 38 cases postoperatively. 2 of
      these 7 relapsed cases underwent additional completion pneumonectomies and
      attained complete cure. Bacteriological relapse-rate was therefore 18.4% (7/38)
      and the ultimate cure rate of pulmonary MDR-Tbc was 88.6% (31/35). (2) 7 patients
      underwent thoracoplasties (not corrective, once for each patient). In 2 cases
      bacteriological relapse was confirmed. Other 5 cases remained bacteriologically
      silent over a long postoperative period. (3) 4 patients underwent cavernostomies,
      3 of them got satisfactory result in reducing the bacterial presence in the
      sputum (preoperative abundant bacilli (Gaffky 7, 8) turned mean-negative within 2
      months after cavernostomy). CONCLUSION: With the above-mentioned results we
      conclude that surgical treatment is highly effective in intractable pulmonary MDR
      Tbc cases.

PMID- 9038014
TI  - [The role of surgery for chronic empyema of the advanced ages].
AB  - Chronic empyema, a sequelae of pulmonary tuberculosis, is now a only tuberculosis
      related disease which was remained to be treated surgically. The candidates who
      have basically poor respiratory function are now attained advanced age. Over a 15
      years period (1980-95), 22 patients 70 years of age or older underwent surgical
      intervention for chronic empyema at our hospital. There were 17 men and 5 women,
      ranging from 70 to 80 years of age (median age 75.0). They were 15.3% of all 145
      surgically treated patients during same period. The empyema continued latent from
      25 to 58 years (average 39.8 years). On admission they complained of productive
      cough (9), fever (9), hemosputam (5) and mass on the chest wall. Their Hugh
      Johnes classification for dyspnea was I.: 4, II.: 6, III.: 11, IV.: 1
      respectively. Their %VC ranged from 31.5 to 79.0 (average 54.8). In fifteen
      patients, tubercle bacilli (5), aspergillus (3) and other bacteria (9) were
      discovered in the empyema space. Surgical procedures consisted of 1 pneumonectomy
      (4.5%), 12 decortication or curettage of empyema wall (54.5%), 4 extraperiosteal
      air plombage (18%) and 5 other procedures (muscle or omental plombage,
      thoracoplasty, fenestration and others) (22.7%). There were no operative death
      and no lethal postoperative complication. In contrast, lethal postoperative
      complications such as GVIID, MOF and gastrointestinal bleeding occurred in the
      younger group. There were 2 cases of late respiratory failure in 70 years or
      older and 6 cases in younger group. Seventy-four years man who, preoperative %VC
      33.0, underwent pneumonectomy died of asphyxia 6 month postoperatively. Another
      74 years man who, preoperative %VC 76.1, developed respiratory failure after
      relapse of pulmonary tuberculosis. Four patients of younger group who developed
      late respiratory failure had all received thoracoplasty as a second operation.
      Other 2 patients, preoperative %VC 33.0 and 27.4 respectively, had undergone
      pneumonectomy. The risk of lethal postoperative complication or late respiratory
      failure were dependent mainly on preoperative respiratory function or surgical
      procedure selected rather than the age of patients.

PMID- 9038015
TI  - [Surgical treatment for tracheobronchial tuberculosis].
AB  - We treated thirty nine patients with tuberculous tracheobronchial stenosis. Age
      varied from 22 to 53 years old (mean 32y.o.). Thirty one were female and eight
      were male. Main stenotic sites of the tracheobronchus were trachea in 3 cases,
      tracheal bifurcation in 2 cases, right main bronchus in 6 cases, left main
      bronchus in 25 cases, right intermediate bronchus in 2 cases, right lower lobe
      bronchus in 1 case. The modes of operations were tracheal sleeve resection + 1t.
      pneumonectomy + T tube insertion to the trachea in 1 patient, laser irradiation +
      T tube insertion to the trachea in 2 patients, carinal reconstruction in 2
      patients, bronchial dilatation by Gebauer in 1 patient, left sleeve upper
      lobectomy in 13 patients, sleeve resection of the left main bronchus in 9
      patients, sleeve resection of the left main bronchus + left upper lobectomy in 2
      patients, right upper sleeve lobectomy in 5 patients, right upper wedge lobectomy
      in 1 patient, sleeve resection of the right intermediate bronchus in 2 patients,
      right S6 sleeve segmentectomy in 1 patient. One patients died of pulmonary edema.
      Anastomotic stenosis occurred in 4 patients. We conclude tracheobronchial
      reconstruction and stent tube therapy is very useful technic for preserve
      pulmonary function in patients with tracheobronchial tuberculosis.

PMID- 9038016
TI  - [Surgical treatment for patients with atypical mycobacteriosis].
AB  - We have been conducting surgical therapy for patients with atypical pulmonary
      mycobacteriosis (AM) since 1965 and have reported on the outcome of this approach
      to treatment. We have found that chemotherapy is not adequately efficacious
      against type III Mycobacterium avium complex (MAC), which suggests that surgical
      intervention may be the optimum approach for MAC. Among MAC patients who were
      treated surgically at our hospital in the period between 1966 and 1994, 74 cases
      on whom postoperative follow-up observation was possible served as the subjects
      of the present investigation. We report here on the outcome of treatment and
      related problems in these patients. Thirty-nine patients gave positive results
      for bacterial discharge on smear tests and all were positive on culture.
      Operation was performed on the right lung in 46 patients and on the left lung in
      16. Pneumonectomy was conducted in 10 patients and lobectomy in 20. Other
      operative modes used included segmental resection in 9, pyothorax in 7, and
      thoracoplasty in 5 patients. Postoperative bacterial excretion was observed in 15
      patients and was persistent bacterial discharge were advanced cases with lesions
      in another lobe, cases with a past history of tuberculosis, cases of cavitation
      with lesions on the contralateral side or cases with massive bacterial discharge
      prior to surgery. Postoperative death occurred in 5 patients: the cause of death
      was lung cancer in 1 case, serum hepatitis in 1 case, and respiratory failure
      evidenced by enlarged shadows in 3 cases. These findings pointed to a marked
      significance of surgical therapy for MAC patients. However, recurrent bacterial
      discharge has been observed occasionally in some patients even 5 years after
      surgery. This suggests the need for careful ongoing assessment of the efficacy of
      surgical therapy and long-term postoperative follow-up.

PMID- 9038017
TI  - [The indication of surgical management in patients with pulmonary disease caused
      by Mycobacterium avium-intracellulare complex].
AB  - The surgical management of patients with nontuberculous Mycobacteriosis caused by
      Mycobacterium avium complex (MAC) was studied regarding the following cases: (1)
      We investigated whether there had been an appropriate time for surgical
      management of patients with MAC who had not responded to medication and who died
      after their conditions became worse retrospectively. During the past 10 years, 49
      patients diagnosed with MAC died at the Toneyama national hospital. 26 patients
      of them died of respiratory failure, apparently due to the worsening of MAC.
      Excluding 2 patients who were extremely elderly, we investigated whether surgical
      management could have been applied in the remaining 24 patients. We found that
      surgical management would have been possible in only one patient, and that at the
      time of diagnosis of MAC in 23 patients, surgical management was already not
      possible. (2) There are patients with MAC who do not respond to medication and
      who continue to excrete bacilli, chest X-ray findings gradually become worse for
      several years. In 1989 we retrospectively studied chest X-ray findings from MAC
      patients and found that 36 out of 103 patients (35%) showed worsening chest X-ray
      findings. The strains were identified in 44 of the 103 patients by the DNA probes
      method. However, of 37 patients with M.avium (41%), 15 had worsening of chest X
      ray findings, while none out of 7 patients with M. intracellulare had worsening
      of chest X-ray findings. We then observed the clinical course of 37 patients who
      showed continuous excretion of bacilli and whose serotypes had been identified
      (20 with serovars 4, 1 with serovars 6, 6 with serovars 8, 2 with serovars 12, 4
      with serovars 14 and 5 with serovars 16) by using the fast-atom bombardment mass
      spectrometry (FAB/MS). Chest X-ray findings later worsened in 14 (70%) of 20
      patients with serovars 4. Nine of these patients have since died; excluding one
      patient who had liver cancer, eight died of respiratory failure due to worsening
      of MAC. In 17 patients with serotypes except serovars 4, 4 (24%) patients had
      worsening of chest X-ray findings, but none of the 5 deaths in this group were
      due to respiratory failure owing to worsening of MAC. These results suggest that
      it is difficult to establish the indication of surgical management in MAC
      patients, except for patients with repeated hemoptysis at present. The prognosis
      and surgical management of pulmonary disease caused by M. avium complex should be
      considered.

PMID- 9038018
TI  - Clonazepam induced delirium in Bosnia.

PMID- 9038019
TI  - Venous injuries are not all alike.

PMID- 9038020
TI  - Behavior should be addressed.

PMID- 9038021
TI  - Are we dancing alone? Matching medical operational readiness training with
      potential future conflict.
AB  - The United States' national security strategy endorses "humanitarian interests"
      as a justifiable reason to deploy U.S. forces. The Armed Forces Medical Corps
      must adapt its readiness training regimens to include this new type of
      deployment, yet not neglect its primary mission of supporting the fighting forces
      at home and abroad. Military medicine has the opportunity to train combat
      specialties in lesser developed countries, enhancing operational readiness and
      preparing these subspecialists for battlefield deployment to third-echelon care;
      but can military medicine support another training mission? This paper will
      describe and illustrate a conceptual model using actual data to assist medical
      chiefs elucidate the reality of implementing this new program.

PMID- 9038022
TI  - Women in combat: concerns of U.S. Air Force and U.S. Army rated male and female
      aircrew.
AB  - The issue of women flying military aircraft in a combat role has been very
      controversial. We conducted a comprehensive survey, via anonymous questionnaire,
      of all U.S. Army and U.S. Air Force rated female aircrew, with an equal number of
      age- and duty-matched male aircrew. Here we report on the women in combat section
      of the questionnaire: should women be allowed to fly aircraft on combat missions?
      if allowed to do so, should they have the option of doing so? The great majority
      of women (87%) felt that they should be allowed to fly aircraft on combat
      missions, whereas only 41% of the men agreed. If women were allowed to fly in
      combat, both genders felt that women should be forced to do so on an equal basis
      with the men. Major concerns were that there be no quotas, that combat slots be
      opened to the best qualified, and prisoner-of-war concerns. Many women opined
      that they should not be forced to go into combat because they believe men are not
      forced to do so. There seemed to be a great deal of animosity between men and
      women concerning women flying in combat.

PMID- 9038023
TI  - Meeting the challenge of emerging pathogens: the role of the United States Air
      Force in global influenza surveillance.
AB  - Influenza virus is one of the most ubiquitous organisms on the planet, causing
      illness in much of the population each year. The dynamic nature of the influenza
      virus requires similarly dynamic surveillance and prevention initiatives. The
      efforts of national surveillance programs, overseen by the World Health
      Organization and administered by institutions such as the U.S. Centers for
      Disease Control and Prevention, the U.S. armed forces, and 60 to 70 collaborating
      laboratories, annually culminate in the development of effective influenza
      vaccines. The U.S. Air Force's contribution is via Project Gargle, through which
      bases in various locations worldwide conduct active surveillance and submit
      throat swab specimens for virus isolation and characterization; the results of
      these laboratory analyses help determine the composition of the following year's
      influenza vaccine. These collaborative efforts have resulted in an identical or
      close antigenic match between vaccine and epidemic strains in 8 of the last 9
      influenza seasons.

PMID- 9038024
TI  - Sexually transmitted disease control in the armed forces, past and present.
AB  - Sexually transmitted diseases (STDs) present a challenge for military medical
      personnel in their efforts to maintain a ready and healthy force. Many tactics
      have been used in military STD control programs. This paper is a review of the
      literature outlining some past strategies used in the United States military and
      how they have shaped current STD policy. These efforts have included financial
      and administrative penalties, stigmatization and shame, screening programs, and
      sharing of resources with other government agencies. Punishments and
      stigmatization have not proven to be useful strategies and have been eliminated
      from current policy. Cooperation with other government agencies and screening
      programs are examined as tactics that have been found useful and are part of the
      program used by the military today to control not only the traditional STDs, but
      also the more recently discovered human immunodeficiency virus.

PMID- 9038025
TI  - Utilization of Special Forces medical assets during disaster relief: the
      Hurricane Andrew experience.
AB  - Special Forces units and their innate assets are presented as the ideal first
      response unit to natural disasters due to their breadth of skill, speed of
      response, and ability to work independently in remote areas. "Green Beret"
      soldiers are particularly suited to work under the most extreme hardships, with
      little or no supervision, and can demonstrate tremendous amounts of initiative
      and creativity in unique and changing situations. The compact, versatile, and
      adaptable detachments of which Special Forces Groups are composed can serve as
      vital resources in humanitarian and disaster relief operations as well as in
      combat.

PMID- 9038026
TI  - Attitudes of Army nurses toward African American and Hispanic patients.
AB  - A random sample of 86 Army nurses from a major metropolitan area participated in
      a study to investigate their attitudes toward African American and Hispanic
      patients. Information was collected using the Ethnic Attitude Assessment Survey.
      Cronbach alpha for the African American patient was 0.74, with 0.72 for the
      Hispanic patient. Analysis was conducted using one-way analysis of variance,
      Pearson correlation, paired t test, and descriptive statistics. The variables
      examined were gender, educational preparation, ethnicity, nursing experience,
      time in the Army, overseas assignments, and whether cultural diversity content
      was included in the respondent's undergraduate curriculum. Attitudes were
      statistically more positive toward the African American patient than toward the
      Hispanic patient. Females had more positive attitudes than males, but only toward
      the African American patient. Finally, nurses perceived a need for cultural
      understanding when providing care to patients of different ethnic groups.

PMID- 9038028
TI  - Satisfaction of active duty soldiers with family dental care.
AB  - In the fall of 1992, a random, worldwide sample of 6,442 married and single
      parent soldiers completed a self-administered survey on satisfaction with 22
      attributes of family dental care. Simple descriptive statistics for each
      attribute were derived, as was a composite overall satisfaction score using
      factor analysis. Composite scores were regressed on demographics, annual dental
      utilization, and access barriers to identify those factors having an impact on a
      soldier's overall satisfaction with family dental care. Separate regression
      models were constructed for single parents, childless couples, and couples with
      children. Results show below-average satisfaction with nearly all attributes of
      family dental care, with access attributes having the lowest average satisfaction
      scores. Factors influencing satisfaction with family dental care varied by family
      type with one exception: dependent dental utilization within the past year
      contributed positively to satisfaction across all family types.

PMID- 9038027
TI  - Leptospirosis on Oahu: an outbreak among military personnel associated with
      recreational exposure.
AB  - In December 1992, a common-source waterborne outbreak of leptospirosis occurred
      on the island of Oahu in the state of Hawaii. Two male service persons were
      hospitalized with culture-confirmed leptospirosis. Eighteen others had similar
      histories of exposure to the same freshwater swimming site. Although six men
      developed signs and symptoms comparable to those of the two confirmed cases, none
      manifested culture or serologic evidence of leptospirosis. The increased
      incidence of leptospirosis in Hawaii coupled with an increased risk in young
      males characterize the military population in Hawaii as a high-risk population
      with respect to leptospirosis.

PMID- 9038029
TI  - Readiness: observations and comments from a medical team deployment.
AB  - The evolving strategy of the United States in dealing with the changing world
      order calls for a force structure capable of fighting and winning two nearly
      simultaneous major regional conflicts and conducting a range of other military
      operations. Readiness is a key factor in this new strategy. Consequently, major
      paradigm shifts are occurring within the Air Force Medical Service. Maintaining
      current and accurate medical records on personnel to meet deployment requirements
      is a significant challenge. Historically, time and resources are consumed
      determining the deployability of troops prior to a deployment. This adds to the
      cost of doing business and increases the time required to clear the deploying
      team, even though there is an established process to avoid these very problems.
      The experience of a recent medical team deployment to Bosnia is discussed. Future
      directions given the implementation of TRI-CARE, the Preventive Health Assessment
      Program, and the Strategic Health Resourcing Plan are also considered.

PMID- 9038030
TI  - Lisinopril use in a large military medical center.
AB  - The results of a drug use evaluation of lisinopril at a large teaching military
      medical center are reported. Indicators and thresholds were developed and
      approved by the Pharmacy and Therapeutics Committee. The medical charts of 227
      patients for whom lisinopril was prescribed from June 1991 to June 1992 were
      reviewed for appropriateness of prescribing, appropriateness of monitoring,
      occurrence of any adverse drug reactions, and detection of drug interactions.
      Prescribing was appropriate in 97% and monitoring was appropriate in all reviewed
      cases. The most common adverse drug reactions detected were cough (7%),
      hypotension (3%), and rash (2%). Patients were also prescribed several drugs that
      may interact with lisinopril. Lisinopril appeared to be well tolerated and
      efficacious. Forty patients (18%) experienced adverse drug reactions related to
      lisinopril. There did not appear to be any major deficiencies with lisinopril
      prescribing and no corrective action needed to be taken other than educational
      activities for the appropriate use of lisinopril. Information from this drug use
      evaluation is useful in formulary decision making.

PMID- 9038031
TI  - The effects of a 4-day march on the lower extremities and hormonal balance.
AB  - The functional strength, flexibility, and ranges of motion of the lower
      extremities, as well as hormonal balance, estimated by urinary excretion of
      adrenaline and noradrenaline and serum determinations of testosterone and
      cortisol, were studied with six physically active army officers participating in
      a 4-day march totaling 185 km. Catecholamine excretion rates showed cumulatively
      increased sympathoadrenal stress, and the effects on serum testosterone and
      cortisol concentrations were minor. Also, leg measurements showed no signs of
      edema, decreases in flexibility, or decreases in functional strength. Most pain
      (75%) experienced by the subjects was located in the feet and caused by abrasions
      and blisters. Only a small portion of perceived pains (25%) was associated with
      muscle soreness. Serum creatine kinase activity was slightly (ca. 400-650%)
      increased during the marching days. Thus, soldiers who are in good physical
      condition and are accustomed to marching are able to walk four marathons on
      successive days, while carrying 10-kg backpacks, without any major adverse
      effects on the musculature of their lower extremities.

PMID- 9038032
TI  - Efficacy of a brief psychosocial treatment for panic disorder in an active duty
      sample: implications for military readiness.
AB  - OBJECTIVE: The efficacy of a brief cognitive-behavioral treatment for panic in
      military personnel was evaluated. METHOD: Active duty military patients (N = 37)
      presenting at outpatient psychiatry and psychology clinics were randomly assigned
      to immediate or delayed treatment conditions. All patients met Diagnostic and
      Statistical Manual of Mental Disorders criteria for a primary diagnosis of panic
      disorder with or without agoraphobia. RESULTS: At posttreatment, 80% of the
      immediate treatment group, compared to 0% of the delayed treatment group, met
      recovery criteria on all major clinical facets of panic disorder (i.e., panic
      attacks, panic-related worry, phobic avoidance). At follow-up, 75% of the treated
      group continued to meet recovery criteria, suggesting maintenance of treatment
      gains. A majority of those patients (58%) taking benzodiazepines at the start of
      treatment were successfully discontinued by posttreatment. CONCLUSIONS: Brief,
      skill-based treatments for panic disorder are effective for a majority of active
      duty personnel. These treatments may also improve military readiness by
      facilitating benzodiazepine discontinuation.

PMID- 9038033
TI  - Proposed criteria for classifying potential dental emergencies in Department of
      Defense military personnel.
AB  - Dental emergencies have been well documented and evaluated. The results of dental
      emergencies have been lost duty time, decreased unit effectiveness, disruption of
      routine care, and hindrance to the military mission. The potential of dental
      emergencies to reduce combat effectiveness is still a major concern. The current
      U.S. Army and Department of Defense (DOD) military personnel dental
      classification system, as regulated by DOD Instruction 6410.1, places certain
      patients broadly into the potential emergency, class 3 category. Changes are
      needed to make this system more effective and predictive. In addition to various
      acute conditions, more emphasis should be focused on caries- and surgery-related
      problems to identify the majority of individuals at high risk for emergencies.
      Based on an extensive literature review, changes in the current system of
      classification are proposed.

PMID- 9038034
TI  - Applications of predictive environmental strain models.
AB  - Researchers at the U.S. Army Research Institute of Environmental Medicine have
      developed and validated numerical models capable of predicting the extent of
      physiologic strain and adverse terrain and weather-related medical consequences
      of military operations in harsh environments. A descriptive historical account is
      provided that details how physiologic models for hot and cold weather exposure
      have been integrated into portable field advisory devices, computer-based
      meteorologic planning software, and combat-oriented simulation systems. It is
      important that medical officers be aware of the existence of these types of
      decision support tools so that they can assure that outputs are interpreted in a
      balanced and medically realistic manner. Additionally, these modeling
      applications may facilitate timely preventive medicine planning and efficient
      dissemination of appropriate measures to prevent weather- and altitude-related
      illnesses and performance decrements. Such environmental response modeling
      applications may therefore be utilized to support deployment preventive medicine
      planning by field medical officers.

PMID- 9038035
TI  - Spinal cord injury: a 25-year morbidity and mortality study.
AB  - The morbidity and mortality occurring during 25 years following spinal cord
      injury were analyzed. A cohort of 230 patients was selected from the Vietnam Head
      and Spinal Cord Injury Study Registry meeting the following criteria: (1)
      survival beyond triage (72 hours); (2) significant myelopathy; and (3)
      availability of medical records. The military and Veteran's Hospital medical
      records were compiled and reviewed. Additional death records were obtained from
      the Department of Veterans Affairs pension office. The major morbidity problems
      continue to be sepsis related to genitourinary and decubiti sequelae.
      Psychosocial maladjustment and substance abuse were prevalent and created heavy
      health care demand. The most frequent cause of death was sepsis. Suicide in the
      paraplegic group occurred at a rate exceeding by 10 times the frequency reported
      for uninjured peers. Survival after 5 years approached but never reached the rate
      established for uninjured peers.

PMID- 9038036
TI  - The laryngeal mask airway: a survey of its usage in 1,096 patients.
AB  - The frequency and pattern of laryngeal mask airway (LMA) usage in a regional
      general hospital has been studied. Data were collected prospectively by means of
      a standardized record sheet which was completed at the time of anesthetic
      administration. During a 19-month period 10,150 patients underwent surgical
      procedures requiring general or regional anesthesia, of which 1,096 (men/ women:
      791/305, ASA 3 or 4: 350, mean age: 64 years) were managed with the LMA. A
      clinically pattern airway was provided in 99.75% of occasions of whom 44.4%
      breathed spontaneously and 55.3% underwent positive pressure ventilation. The
      monthly frequencies of LMA usage increased significantly during the second year
      of the survey (25.1% vs 12.8%). Problems were recorded in 16.3% of cases: air
      leak 8.0%, laryngospasm 1.8%, desaturation (SpO2 < or = 90%) 1.8%, severe
      hypercarbia (PETCO2 > or = 50 mmHg) 1.0%, regurgitation 0.09%, sore throat 3.4%.
      No patient required intensive care management postoperatively. There were five
      cases of failed intubation managed with the LMA. This survey has shown that LMA
      has a well established role in anesthetic practice. Use of this device is equally
      safe and effective for both controlled and spontaneous ventilation in a wide
      range of starve patients undergoing most types of surgery.

PMID- 9038037
TI  - Calcium antagonists, a useful additional therapy in treatment resistant
      hypertension: comparison of felodipine ER and nifedipine Retard by 24-h
      ambulatory blood pressure monitoring.
AB  - OBJECTIVE: To compare the efficacy and tolerability of felodipine extended
      release (ER) 2.5 mg (F2.5) and 5 mg (F5) once daily with nifedipine Retard 10 mg
      (N20) and 20 mg (N40) twice daily as additional therapy in patients who remained
      hypertensive despite treatment with an ACE-inhibitor, beta-blocker or diuretic.
      DESIGN AND METHODS: In a multicentre, double-blind parallel study, 61 men and 54
      women, aged 35-75, with a supine diastolic blood pressure between 95 and 115 mmHg
      were randomised to treatment with F2.5, F5, N20 or N40 for 8 weeks, with optional
      doubling of the dose after 4 weeks. Blood pressure was measured at the office
      after 0, 4 and 8 weeks and by 24-h ambulatory monitoring (ABPM) after 0 and 4
      weeks. Spontaneously reported adverse events and a subjective symptom assessment
      questionnaire were used for side-effect profiling. RESULTS: Mean office
      systolic/diastolic blood pressure was clinically relevantly reduced in all
      treatment groups after 4 weeks by 8/7, 12/9, 11/9 and 18/11 mmHg for F2.5, F5,
      N20 and N40, respectively, and after 8 weeks (F2.5-5: 17/11 mmHg: F5-10: 18/14
      mmHg; N20-40: 19/14 mmHg; N40-80: 25/14 mmHg) with no statistically significant
      differences between these groups. The lowest dose of felodipine (F2.5) was the
      least effective. After 4 weeks the ABPM showed consistent 24-h reductions in
      blood pressure (4/2; 8/5; 7/5; 10/6 mmHg, respectively) over 24 h for the
      felodipine ER 5 mg group only and for both nifedipine groups. No statistically
      significant difference between these groups was found. An office responder does
      not appear to be identical to an ambulatory one and vice versa. The adverse
      events, mostly oedema, flushing and headache, were dose-related. CONCLUSIONS:
      Both felodipine ER and nifedipine Retard are effective "add-on' drugs in patients
      with monotherapy-resistant hypertension. The blood-pressure-lowering effect is
      dose-dependent and tolerability is inversely related to efficacy. The results
      emphasize the benefits of combining two agents with low doses.

PMID- 9038038
TI  - Hyperventilation syndrome: an elegant but scientifically untenable concept.
AB  - The concept of hyperventilation and the principle of a vicious circle provide an
      elegant explanation for the development of a wide range of somatic and
      psychological symptoms, the so-called hyperventilation syndrome (HVS). The model
      has a high degree of credibility and has led to the development of therapeutic
      interventions that appeared beneficial. However, recent investigations dismiss
      hyperventilation as an important symptom-producing mechanism. First, the
      hyperventilation provocation test appears to be invalid as a diagnostic test.
      Second, studies using ambulant monitoring of pCO2 demonstrate that the vast
      majority of real-life attacks are not attended by decreases in pCO2. Third, the
      evaluation of therapy outcome studies indicate that the beneficial effect of
      breathing retraining is probably not mediated by reducing the tendency to
      hyperventilate. We conclude that a diagnosis of HVS should be avoided.

PMID- 9038039
TI  - Mannitol-induced acute renal failure.
AB  - Mannitol is widely used because of its osmotic diuretic action and its presumed
      antioxidant properties. In pre-existent renal dysfunction, however, mannitol may
      accumulate leading to potentially deleterious effects. We describe a 71-year-old
      woman with moderate chronic renal failure due to diabetic nephropathy who
      developed acute anuric renal failure after mannitol administration for post
      traumatic reflex sympathetic dystrophy. After haemodialysis symptoms of acute
      renal failure rapidly disappeared with recovery of pre-existent renal function.
      Daily measurement of the osmolal gap as a simple and accurate way of monitoring
      patients receiving mannitol infusion is emphasized. A rapid increase in the
      osmolar gap should prompt adjustment of the dose or even discontinuation of
      mannitol, especially in the case of pre-existent risk factors.

PMID- 9038040
TI  - Carbamazepine-associated acute tubulointerstitial nephritis.
AB  - The case history of a patient developing tubulointerstitial nephritis (TIN)
      during carbamazepine therapy is described. After withdrawal of the drug and
      introduction of prednisone renal function normalised. TIN is a rare side-effect
      of carbamazepine of which only a few cases have been described. There seems to be
      a remarkable time interval of 2 months between the onset of therapy with
      carbamazepine and the development of TIN.

PMID- 9038041
TI  - Agenesis of the corpus callosum associated with paroxysmal hypothermia: Shapiro's
      syndrome.
AB  - Spontaneous recurrent hypothermia and hyperhidrosis associated with agenesis of
      the corpus callosum was first described by Shapiro and Plum in 1967. Since then,
      several cases with similar symptoms (now known as Shapiro's syndrome or
      spontaneous periodic hypothermia) have been described. We report another case of
      this syndrome in a 21-year-old-man, and discuss possible pathogenetic mechanisms
      and therapeutic approaches.

PMID- 9038042
TI  - New developments in the treatment of deep venous thrombosis.
AB  - An initial course of standard heparin (SH) or low-molecular-weight heparins
      (LMWH) is regarded as the treatment of choice for patients with deep venous
      thrombosis (DVT). LMWH have better bioavailability after subcutaneous
      administration, have a longer half-life, and show higher and more predictable
      anticoagulant activity. As a result they can be given subcutaneously and without
      laboratory control, using a dose that is determined by bodyweight. Because of
      these multiple advantages of LMWH they will replace SH in the future and
      subsequently home treatment with LMWH of selected patients seems feasible. The
      currently accepted approach is to start with SH or LMWH therapy combined with
      oral anticoagulant therapy. (OAT) at the time of diagnosis. The course of SH or
      LMWH should continue for at least 5 days, provided that international normalized
      ratio (INR) is in the therapeutic range on 2 consecutive days. OAT should be
      continued for at least 3 months to prolong the prothrombin time to an INR of 2-3.
      When oral anticoagulants are either contraindicated or inconvenient, SH or LMWH
      can be used at the middosing interval. The role of anti-platelet treatment is not
      yet established and should be compared with coumarin therapy in the future.

PMID- 9038043
TI  - Lessons from emergency care.

PMID- 9038044
TI  - Tomorrow today.

PMID- 9038045
TI  - Self-reported dental status and treatment need among elderly people.
AB  - A convenience sample of 180 elderly residents of Council flats in Wanganui were
      interviewed about their dental health and experiences of dental care. Thirty
      percent of the sample were dentate, and this was higher among younger subjects.
      Life-long or mostly life-long dental attendance was reported by 43 percent, and
      this was higher among individuals of higher socioeconomic status and those who
      had been educated to secondary school level or more. Life-long attenders were
      more likely to be dentate. Approximately one-third of subjects reported a current
      problem or dental treatment need.

PMID- 9038046
TI  - Obstructive sleep apnoea. Part I: Diagnosis, aetiology, and current treatment.
AB  - Obstructive sleep apnoea is a multi-factorial condition associated with high
      morbidity and mortality. Its prevalence is highest in middle-aged males with a
      predisposition to obesity. Certain facial types have been identified as being at
      risk. Cephalometric parameters have now been established to identify those
      patients who are anatomically compromised. Treatment modalities are dependent on
      the correct diagnosis of the site(s) of obstruction. Overnight polysomographic
      testing is the only definitive measure to quantify the presence and severity of
      obstructive sleep apnoea. Treatment options include behavioural, medical,
      surgical, and the use of oral appliances.

PMID- 9038048
TI  - [Renal cell carcinoma--clinicopathological characteristics and future aspects].

PMID- 9038047
TI  - Dental disease levels and reasons for emergency clinic attendance in patients
      seeking relief of pain in Auckland.
AB  - This study examined the reasons for attendance, duration of the problem,
      treatment expectations and oral health of patients seeking relief of pain at
      Auckland hospital dental departments and a private accident and emergency clinic.
      One-third of hospital-clinic participants and 15 percent of private-clinic
      participants had delayed treatment for more than 1 month. Sixty-three percent of
      hospital-clinic and 30 percent of private-clinic participants expected to receive
      an extraction. The hospital-clinic group had a mean of 5.0 (SD 3.9) decayed
      teeth, and the private clinic group a mean of 2.3 (SD 2.8) decayed teeth.
      Periodontal treatment needs were also significantly higher among participants
      attending the hospital clinics. Twenty-five percent of hospital-clinic
      participants had complex periodontal treatment needs. Further research is
      required to estimate the size of the population these groups represent and to
      investigate the reasons for these differences.

PMID- 9038049
TI  - [Adhesive properties of bacteria isolated from patients with urinary tract
      infection to the urinary bladder].
AB  - BACKGROUND: Clinically isolated Staphylococcus epidermidis KK3-75, Enterococcus
      faecalis SMU-14, and Escherichia coli TF6-27 were subjected to test for bladder
      lodgments. METHODS: Experimental cystitis on mice was investigated pathologically
      by light, confocal laser, and electron microscope after intravesical injection of
      cell suspensions of the strains. Bacterial affinities with bladder mucosal
      proteins and with extracellular components were detected by Western blot
      analysis. RESULTS: Pathological findings of experimental cystitis revealed
      prominent infiltration of neutrophils except for those that were challenged with
      Enterococcus faecalis SMU-14. Capsule-like structures were demonstrated for the
      other two strains. Each strain showed histological tropism within the tissue
      sections, which correlated with the capability to bind the respective
      extracellular matrix components tested. Type I collagen bound only to cellular
      extracts of Enterococcus faecalis SMU-14 and Escherichia coli TF6-27, whereas
      fibronectin and type IV collagen bound only to those of Staphylococcus
      epidermidis KK3-75 and Enterococcus faecalis SMU-14. Bladder mucosal proteins had
      a variety of ability to bind cell surface proteins of each strain. Bacterial cell
      surface binding of all except for two of the bladder mucosal proteins detected
      was inhibited by extracellular matrix components. CONCLUSION: These experimental
      results suggest that the bacterial affinity of the bladder restricted by strain
      specific cell surface properties may be important for explanation in the
      difference of occurrence and progression of urinary tract infections caused by
      each strain.

PMID- 9038050
TI  - [Foreskin retraction for phimosis of the newborn].
AB  - BACKGROUND: No guideline exists on how to treat boy's phimosis. We examined if
      retraction of the foreskin of the newborn boy's penis could make true phimosis
      become false phimosis. METHODS: We taught the mother to retract the foreskin and
      keep inside the foreskin clean. Exposure degree of glans by retraction of
      foreskin was defined in 7 grades, 0 (none) approximately III (middle)
      approximately VI (full). RESULTS: Of the 538 newborn examined, none had full
      exposure (VI). All of the 372 cases who continued the procedure, including 2
      buried penis, gained full exposure (VI). Average time for full exposure according
      to the first degree of exposure was 2.94 months (0), 1.78 months (III), 1.22
      months (V), 2.32 months average, respectively. No serious complications occurred.
      CONCLUSION: Retraction of the foreskin from the newborn period made all the true
      phimosis to be false phimosis and operative procedures became unnecessary.

PMID- 9038051
TI  - [Study of directional differences on static and stress urethral pressure profiles
      of female urethra].
AB  - PURPOSE: We investigated the female continence mechanisms by comparing
      directional differences of static and stress urethral pressure profiles (UPP) in
      urinary continent females with those in stress incontinent females. Also, the
      mechanisms of bladder neck suspension were investigated by comparing directional
      differences of UPP pre- and post-operatively. METHODS: UPP at rest and under
      stress were recorded by means of double lumens microtip transducer catheter in 21
      females without urinary incontinence (normal group) and 38 females with stress
      urinary incontinence (SUI group). And UPP were recorded pre- and postoperatively
      in 19-females of SUI group who had surgical cure of SUI (ope group). These
      measurements were performed on the urethral directions (anterior-direction of
      symphysis pubis, lateral and posterior) to which the pressure sensor in the
      catheter were pointed. Pressure transmission ratios (PTR) were calculated in each
      quartile dividing functional urethral length (FUL) into four equal lengths. We
      compared the parameters (the maximum urethral closure pressure = MUCP, FUL and
      PTR) when the sensor lies at the anterior, lateral and posterior direction in
      each group. The parameters in normal group were compared with those in SUI group
      in each direction and those in ope group were, compared pre- and postoperatively.
      RESULTS: In all groups, MUCP is always highest in the anterior direction but FUL
      shows no differences in the three directions. In all directions, MUCP and FUI are
      higher in the normal group than in the SUI group and there is no significant
      change in MUCP and FUL following successful bladder neck suspension. In the
      normal group, PTR of anterior, lateral and posterior urethra were approximately
      equal, but SUI group patients demonstrated significantly decreased PTR in the
      lateral and posterior urethra in comparison with PTR observed in the anterior
      urethra. Also, PTR of the anterior urethra in the SUI group approximates that in
      the normal group but PTR of the lateral and posterior urethra are lower in the
      SUI group than in the normal group. In the ope group, in the proximal three
      quarters of the FUL, PTR in the lateral and posterior urethra approximated to
      those in the anterior urethra postoperatively. CONCLUSION: These findings suggest
      that urethral support is destructed in the SUI group as mentioned in DeLancey's
      hammock hypothesis and lateral and posterior weakness were corrected by bladder
      neck suspension. Bladder neck suspension restored the continence by constructing
      posterior support of urethra as the substitution for destructed urethral support.

PMID- 9038052
TI  - [Study on the surgical treatment for pulmonary metastasis from renal cell
      carcinoma].
AB  - BACKGROUND: Pulmonary resection for metastatic renal cell carcinoma were studied
      to assess the indication of surgical management. METHODS: Between January, 1981
      and December 1994, 17 consecutive patients (14 men and 3 women) underwent
      complete pulmonary resection for metastatic renal carcinoma. Median age was 61
      years (range, 45 to 73 years). Eleven were appeared lung metastasis after
      resection of primary tumor. Median time between nephrectomy and pulmonary
      resection was 32 months (range, 0 to 127 months). RESULTS: There were no
      operative deaths. One patient had solitary metastasis, 4 had two, 2 had three, 2
      had four, one had seven, one had eight and 6 had more than twenty-two. Segmental
      resection was performed in 12 patients, lobectomy in 2, lobectomy and
      segmentectomy in 3 and segmentectomy for total lobes in 3. Four patients had
      another site operation of renal metastasis, brain tumor resection, chest wall and
      ribs resection, contra-lateral adrenalectomy and contralateral partial
      nephrectomy. Median follow-up was 44 months (range, 10 to 129 months). The cause
      specific survival rate and disease free survival after pulmonary resection was 55
      and 48 percent at 5 years and 27 and 14 percent at 10 years, respectively.
      CONCLUSION: Pulmonary resection for metastatic renal cell carcinoma was
      considered effective in some selected slow-growing cases. Multiple and both lungs
      metastases is not contraindication and the patients under 10 metastatic focuses
      had good prognosis.

PMID- 9038053
TI  - [Urinary neopterin levels in patients with genitourinary tract malignancies].
AB  - BACKGROUND: Neopterin is released from macrophages upon stimulation with gamma
      interferon, secreted by activated T cell. Therefore it has been recognized as a
      useful indicator of the activation of the T cell-macrophage system. Increased
      neopterin levels are observed in patients with acute graft rejections, viral
      infections, auto-immune diseases and several malignancies. Urinary neopterin
      concentrations were determined in patients with genitourinary tract malignancies
      to evaluate the usefulness of neopterin as a tumor marker. METHODS: Urinary
      neopterin concentrations were determined by high-performance liquid
      chromatography in 90 patients with genitourinary tract malignancies and 28
      patients with benign urological tumors and 34 healthy subjects. RESULTS:
      Increased urinary neopterin levels were observed in 52% of the patients with
      genitourinary tract malignancies and 7% with benign urological tumors. The
      positivity rate in patients with renal cell carcinoma (RCC), renal pelvic and
      ureteral tumor, bladder tumor (BT), prostatic carcinoma (PC) and testicular tumor
      was 68%, 80%, 47% and 30%, respectively. The difference in the urinary neopterin
      levels between low and high stages was highly significant (p < 0.0005) in
      patients with RCC (stage I-II vs. stage III-IV) and BT (T1S-1 VS. T2-4). The
      urinary neopterin levels were also correlated with the tumor grade in patients
      with RCC and PC. CONCLUSION: Our study suggests that urinary neopterin levels may
      supplement laboratory examinations for patients with genitourinary tract
      malignancies, providing useful information in evaluating the tumor stage and
      follow-up of the disease.

PMID- 9038054
TI  - [Continent urinary reservoir using dilated renal pelvis of non-functioning pelvic
      kidney in a girl with cloacal exstrophy].
AB  - We performed construction of continent urinary reservoir in an 8-year-old girl
      with cloacal exstrophy who had double stoma of ileostomy and colon conduit.
      Preoperative evaluation revealed non-functioning right kidney with severely
      dilated renal pelvis and calyxes in her pelvis. Urinary reservoir was constructed
      using detubularized colon segment which had been used as the urinary conduit and
      dilated renal pelvis of non-functioning pelvic kidney. Using Mitrofanoff's
      principle, continent catheterizable channel was also made of the anterior wall of
      the renal pelvis. Postoperative course was uneventful. Reservoir capacity
      increased to 350 ml one and half year postoperatively and she is almost dry with
      clean intermittent catheterization 5 times a day. Dilated upper urinary tract is
      one of the ideal material for bladder enlargement that avoids the complication
      associated with the use of gastrointestinal tract.

PMID- 9038055
TI  - [US-guided core biopsy of the breast with an automated biopsy gun: comparison
      with an aspiration core needle device].
AB  - To evaluate the efficacy of an automated Tru-cut type of biopsy gun in US-guided
      breast biopsy, we performed 162 breast biopsies in 148 patients using an 18 gauge
      short-throw (1.1cm excursion) Tru-cut-type biopsy gun (Ace-cut needle). The
      results of the series were compared with another series of aspiration core
      biopsies, which were performed on 113 breast lesions in 112 patients using an 18
      gauge Sure-cut needle. The results of the two series were correlated with the
      diagnoses made at surgery or clinical follow-up. Sensitivity, specificity, and
      accuracy for the automated biopsy gun were 89.2%, 94.9%, and 92.7%, and for the
      Sure-cut needle, 75.0%, 78.6%, and 77.5%, respectively (p < 0.01 for specificity
      and accuracy, by chi 2 test). There were no serious complications. The diagnostic
      surgical biopsy to operated cancer ratios in 1991 (without core biopsy), 1993
      (with aspiration core biopsy), and 1995 (with automated core biopsy) were 2.9
      (46/10), 2.0 (30/17), and 0.5 (12/24), respectively. We concluded that US-guided
      breast biopsy with an automated biopsy gun is a safe and highly accurate method,
      and could replace the diagnostic surgical biopsy.

PMID- 9038056
TI  - [Diagnostic imaging of renal pedicle injury].
AB  - We reviewed the radiological findings of 8 patients with renal pedicle injury
      admitted to our emergency center from January 1986 through September 1995 and
      compared them with the previously reported findings. The patients included 3 with
      renal artery occlusion and 5 with avulsion or disruption of renal pedicle
      vasculature. Extended retroperitoneal hematoma such as contralateral pararenal or
      central parahilar hematoma was visualized in all 5 cases with avulsion or
      disruption of renal pedicle vasculature. Although lack of contrast enhancement of
      injured renal parenchyma is a hall-mark of renal pedicle injury, three cases did
      not demonstrate this typical finding. In these three cases, one showed partial
      and the others showed total enhancement of the injured renal parenchyma on
      contrast enhanced CT. Partial enhancement in one case was found to represent
      total occlusion of the main renal artery and an intact accessory polar branch on
      angiography. The other two cases showed total enhancement of the renal
      parenchyma, with renal vein perforation done and complete disruption of the main
      renal artery and vein in the other. The latter findings were thought to be due to
      the maintenance of vascular flow surrounded by hematoma. In conclusion, when
      central parahilar hematoma is identified, the possibility of renal pedicle injury
      should be considered even if the renal parenchyma is well enhanced.

PMID- 9038057
TI  - [Examination of scanning technique for lung cancer screening with helical CT].
AB  - As a new application of helical CT scanning we evaluated the parameters for lung
      cancer screening with an extremely low doses and large helical pitch. On the
      phantom studies, the image quality obtained with the low dose parameter was not
      inferior to that of the usual screening technique but artifacts were increased
      with the large helical pitch. A scanning technique using 120 kv, 40-60mA, 10mmth,
      20mm/ sec, and a reconstruction pitch of 2 was used for lung cancer screening
      (screening parameters) (50 cases), and comparison was made between the
      detectability of the screening parameters and the routine parameters (120 kv,
      200mA, 10mmth, 10-13mm/sec, and a reconstruction pitch of 1-1.3). Detectability
      with the screening parameters was as follows: nodular lesions (< 5mm in size:
      76%. 5-10mm: 90-93% 10mm < 100%), linear lesions: 94-95%, infiltrations: 93-100%.
      There were no false negative lesions, when the reconstruction pitch of the
      screening parameters was changed from 1 to 0.25. In conclusion, reconstruction
      pitch had the most influence on lesion detectability.

PMID- 9038058
TI  - [Preliminary evaluation of the apparent diffusion coefficient of the kidney with
      a spiral IVIM sequence].
AB  - We examined the usefulness of the spiral intravoxel incoherent motion (IVIM)
      sequence in measuring the apparent diffusion coefficient (ADC) of the kidneys.
      Five volunteers and five patients with chronic renal failure underwent diffusion
      sensitive magnetic resonance imaging of the kidneys with the spiral IVIM
      sequence. The ADC values in patients with chronic renal failure were
      significantly lower than those in the renal cortex of volunteers. The mean value
      of ADC in patients with chronic renal failure was lower than that in volunteers,
      although there was no statistically significant difference. In volunteers, the
      ADC of the renal cortex was significantly higher than that of the renal medulla.
      The phantom study indicated that the accuracy of ADC depended on the signal to
      noise ratio. A spiral IVIM sequence with a high enough signal to noise ratio may
      be useful in evaluating renal function especially that of the cortex.

PMID- 9038060
TI  - [Prognostic factors of cervical carcinoma treated with postoperative
      radiotherapy].
AB  - We analyzed 119 patients with cervical carcinoma treated by postoperative
      radiotherapy from 1983 to 1993. Five- and 10-year survival rates of all patients
      were 77% and 67%, respectively. The 10-year survival rates for stage I (54
      patients) and stage II (65 patients) were 76% and 58%, respectively. Ten-year
      survival rate for patients with both deep stromal invasion and lymph node
      metastasis was 37% which was much lower than in those without them (more than 90
      %), indicating that they seemed to be factors related to poor prognosis. The
      results of multivariate analysis showed that the number of metastatic lymph nodes
      was the most important prognostic factor. Leg edema and intestinal and urinary
      insufficiency as late complications of postoperative radiotherapy occurred at low
      incidences and were well tolerated.

PMID- 9038059
TI  - [Uterine cervical carcinoma after radiotherapy: comparison between MR imaging and
      histopathological findings].
AB  - The findings of MRI and pathologic investigation were correlated in curatively
      irradiated uterine cervical carcinoma. Four patients having residual carcinoma
      diagnosed by biopsy underwent hysterectomy. MRI demonstrated the mass lesion in
      one patient with pathologic confirmation of massive viable cancer cells (case I).
      Of the other three patients, MRI demonstrated normal configuration of the uterine
      cervix. Cervical signal intensity, however, varied. Hyperintensity was noted in
      an area of the posterior wall on T2WI in case 2. The anterior wall of the case 2
      and the other two cases showed hypointensity. Cervical specimens with normal
      intensity showed only a small number of degenerated cancer cells. On the other
      hand, pathologic examination of the posterior wall of the case 2 revealed both
      cancer cells with varying degrees of degeneration and necrotic tissues.
      Degeneration of cancer cells was stronger in the superficial layer than the
      deeper layer. Fibrosis, hemorrhage, granulation and hyalinization were
      hypointense on T2WI. T2 elongation reflected not only the residual tumor but the
      post-irradiation changes. Post-irradiated cervix with normal intensity indicated
      that only a small number of degenerated cancer cells may persist even if the
      biopsy was positive. We conclude that MRI is useful in evaluating tumor response
      to radiotherapy.

PMID- 9038061
TI  - [Treatment results of brain metastasis from breast cancer: course of the disease
      and radiation therapy].
AB  - Thirty-nine patients with brain metastasis from breast cancer who were treated in
      our hospital between 1978 and 1992 and followed up until November 1995 were
      reviewed. The initial diagnosis of brain metastasis and follow-up were made by
      MRI and/or CT. Extracranial metastases were found in 90% of the patients and were
      the cause of death in 89%. Treatments included surgery alone in 2 patients (group
      S) surgery plus postoperative radiotherapy in 8 (group SR), radiotherapy alone in
      28 (group R) and conservative therapy in 1 (group C). Radiotherapy of up to 40Gy
      to the whole brain was carried out, but was performed in only 75% of patients in
      group R. The overall median survival was 5.4 months with a 1-year survival rate
      of 23% and a two-year rate of 10%. In patients treated with over 40Gy, the
      survival time for radiotherapy alone was 5.1 months, with a 1-year survival rate
      of 9.5%; relief of specific neurologic symptoms was noted in 80%. The longest
      survival was noted in a patient with a single brain metastasis, who, to date, has
      survived for five years and two months following 60Gy of irradiation. Patients
      with the following clinical conditions should have a good prognosis: (1) no
      further metastases in other sites, or well controlled if existing, (2) no
      symptoms of NF (neurological function: RTOG) or slight, and improved NF by
      treatment, (3) surgical candidate, (4) good response to initial treatment on CT
      or MRI. Despite a bad prognosis in general, brain metastasis from breast cancer
      can be treated affirmatively, if these clinical conditions are fulfilled.

PMID- 9038062
TI  - [Assessment of cerebral benzodiazepine receptor distribution in anxiety disorders
      by 123I-iomazenil-SPECT: comparison to cerebral perfusion scintigraphy by 123I
      IMP].
AB  - 123I-Iomazenil (123I-IMZ) and 123I-IMP imaging were performed in 5 patients with
      anxiety disorder (PAD) and 6 normal volunteers (NV). On 123I-IMZ delayed imaging,
      the 2 PAD showed abnormally decreased findings. In anxiety disorder, decreased
      accumulation on 123I-IMZ delayed images was seen in left hippocampus and
      parahippocampal gyrus in one patient, in right frontal and temporal lobe and left
      occipital pole in the other. Compared with NV, PAD had lower 123I-IMZ uptake on
      delayed image in right upper and left lower frontal cortices, indicating the
      involvement of the benzodiazepine receptor complex in anxiety disorder. Compared
      with grading for anxiety disorder with Hamilton anxiety scale (HAS) and delayed
      to early count ratios of 123I-IMZ, negative correlation (R < -0.7) was recognized
      hippocampus and parahippocampal gyrus, frontal and occipital cortices. Compared
      between HAS and the count ratio to the cerebellum on 123I-IMP image, positive
      correlation (R > 0.7) was recognized in the hippocampus, the parahippocampal
      gyrus, the lower outer temporal cortex and the lower frontal cortex.

PMID- 9038063
TI  - [Assessment of cerebral benzodiazepine receptor distribution in epilepsy by 123I
      iomazenil-SPECT].
AB  - 123I-Iomazenil (123I-IMZ) and 123I-IMP imaging were performed in 8 epileptic
      patients (EP) in the interictal phase and 6 normal volunteers (NV). On 123I-IMZ
      delayed imaging, the 8 EP showed abnormally decreased findings. Two EP showed
      decreased perfusion in the same region on 123I-IMP imaging. 123I-IMZ imaging for
      the detection of epileptic foci showed relatively high specificity compared with
      EEG recording. On 123I-IMZ early images, the count ratio of the right lower
      frontal cortex was lower the cerebellar cortex in EP was lower than that in NV.
      On 123I-IMZ delayed images, the count ratio of the bilateral occipital and the
      right upper and lower frontal cortices to the cerebellar cortex in EP was lower
      than that in NV. On 123I-IMZ delayed images, the count ratio of the right upper
      frontal cortex to the occipital cortex in EP was lower than that in NV. On 123I
      IMZ delayed images, the count ratio of the left lower frontal cortex to the
      occipital cortex in EP was higher than that in NV. These results pointed to the
      involvement of the benzodiazepine receptor complex in epilepsy.

PMID- 9038064
TI  - [Evaluation of 99mTc-ECD SPECT for the detection of brain tumor: comparison with
      201TI SPECT].
AB  - For the evaluation of brain tumor (n = 15), we performed both dynamic and static
      99mTc-ECD (ECD) SPECT studies 201Tl SPECT was also used for comparison with the
      results of ECD SPECT. Dynamic ECD SPECT was obtained following the injection of
      600 MBq of ECD. Five min after the injection of ECD, static ECD SPECT was
      performed. 201Tl SPECT was obtained 10 min after the injection of 74MBq. Abnormal
      uptake was recognized in 7 of 15 tumors with dynamic ECD: 5 of 7 meningiomas, 1
      of 1 glioblastoma and 1 of 1 astrocytoma. However, no abnormal uptake was seen in
      3 of 3 benign tumors (1 low grade astrocytoma, 1 hemangioma, 1 cranio
      pharyngioma) and in 2 of 2 brain metastases. In contrast abnormal uptake was seen
      in 11 of 15 tumors with 201Tl:7 of 7 meningiomas; 2 of 2 brain metastases, 1 of 1
      glioblastoma and 1 of 1 craniopharyngioma. No abnormal uptake was seen in 3 of 3
      benign tumors (1 hemangioma and 2 low grade astrocytomas). Equivocal uptake was
      seen in 1 low grade astrocytoma with dynamic ECD and 201Tl. The mechanism of the
      accumulation of dynamic ECD to brain tumor is unclear. However, it may reflect
      not only blood flow, but also metabolism.

PMID- 9038065
TI  - [High resolution MR imaging of the hip using pelvic phased-array coil].
AB  - A pelvic phased-array coil was applied to obtain high resolution MR images of the
      hip. Three-mm-thick fast spinecho images were obtained in seven hips. Images with
      a pelvic coil enhanced delineation of acetabular labrum and articular cartilage
      more clearly than those with a body coil or flexible-surface coil. The use of a
      pelvic coil in imaging of the hip may be of diagnostic value because of its
      superior delineation.

PMID- 9038066
TI  - [MR dynamic subtraction angiography (MRDSA)].
AB  - We have developed magnetic resonance dynamic subtraction angiography (MRDSA),
      which depicts the long segments of arteries from the upper abdomen to the lower
      leg by using a small dose of Gd-DTPA. The lower half of the body was divided into
      three imaging regions, abdomen, thigh and lower leg, in the order of scanning.
      The contrast-enhanced three-dimensional breath-hold fast field echo technique
      with half Fourier acquisition was performed in 3 normal volunteers and 12
      patients with vascular diseases (4: abdominal aortic aneurysm, 8: atherosclerotic
      occlusive disease). The images were reconstructed into composite images by using
      maximum-intensity-projection postprocessing after the subtraction of precontrast
      images. A bolus intravenous injection of a small dose of Gd-DTPA (0.02-0.05
      mmol/kg) was given, followed by the five sets of scans. The acquisition time of
      each set was 8 to 16 seconds, and the total dose used in MRDSA was 0.1 to 0.15
      mmol/kg. The image quality of MRDSA was satisfactory in 3 normal volunteers and
      12 patients with vascular diseases. MRDSA demonstrated aortic aneurysm and
      atherosclerotic obstruction as clearly as conventional angiography. MRDSA can
      replace conventional angiography.

PMID- 9038067
TI  - [Evaluation of three-dimensional CT angiography (3D-CTA) for the diagnosis of
      cerebral vasospasm].
AB  - We evaluated the usefulness of three-dimensional CT angiography (3D-CTA) for the
      diagnosis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Eleven
      patients with SAH who were suspected of having cerebral vasospasm on the basis of
      their clinical symptoms were examined by 3D-CTA with a spiral CT scanner after an
      intravenous bolus administration of contrast medium. 3D-CTA revealed vasospastic
      changes of the cerebral vessels in eight patients. Conventional angiography was
      performed in six patients immediately after the 3D-CTA examination, and
      demonstrated the cerebral vasospasm. In eight patients, a second 3D-CTA was
      performed with the same technique one week after the first 3D-CTA examination.
      The second 3D-CTA showed the cerebral vessels without vasospastic change. In
      conclusion, 3D-CTA is a promising, minimally invasive strategy for the assessment
      of cerebral vasospasm.

PMID- 9038068
TI  - [Quantitative evaluation of magnetization transfer ratio in irradiated breast
      with breast conservation therapy].
AB  - To assess the late effects of radiotherapy, magnetization transfer was evaluated
      in 2 patients with breast conservation treatment and in 4 patients without
      treatment. The magnetization transfer ratios (MTRs) were measured from a pair of
      images obtained by the conventional SPGR pulse sequence and the MT-prepared SPGR
      sequence on a 1.5-TMR system. The MTR values of irradiated breast were higher
      than those of non-irradiated breast. The difference in MTR between them was
      considered to represent tissue change due to irradiation. We showed that MTR is a
      useful parameter in estimating the late effects of radiotherapy.

PMID- 9038069
TI  - [Influence of transglottal pressure on vocal fundamental frequency changes with
      stiffness of vocal folds].
AB  - We have described the influence (dF/dP) of transglottal pressure on vocal
      fundamental frequency (F0). It was previously reported that dF/dP varied with the
      stiffness of the vocal folds, and that the vocal fold membrane when dry was
      stiffer than when wet. Normal subjects were injected with atropine sulfate in
      order to dry their larynx, as a model of stiffer-than-normal vocal folds.
      Transglottal pressure changes during sustained phonation were applied by
      partially closing a shutter valve mounted on a mouthpiece. Both before and after
      atropine sulfate injection, the values of dF/dP, in modal register, decreased and
      increased as F0 increased, and the smallest values of dF/dP were negative in all
      subjects. The absolute values of both the largest and smallest dF/dP in subjects
      with atropine sulfate were smaller than those in normal subjects. These finding
      indicated that dF/dP is correlated with the stiffness of the vocal folds.

PMID- 9038070
TI  - [Clinical and pathological study of esophageal mucosa with hypopharyngeal
      cancer].
AB  - Hypopharyngeal cancer has been reported to be frequently associated with cancer
      of the upper gastrointestinal tract, especially the esophagus. We recently
      reviewed the records of patients who had undergone closed-chest esophagectomy to
      assess the value of endoscopy with iodine staining as a means of preoperative
      diagnosis of double cancers in this area and to investigate the characteristics
      of the hypopharyngeal and esophageal mucosa as sites for multicentric
      carcinogenesis. The subjects of this study were 30 patients who had undergone
      closed chest esophagectomy between January 1992 and December 1995 because of
      hypopharyngeal cancer. The following results were obtained: 1. Preoperative
      iodine staining often revealed the presence of cancer, with unstained areas
      covering more than half the circumference of the esophagus and being more than 3
      cm in size. 2. Esophageal cancer and hypopharyngeal cancer were detected
      concurrently in 15 cases (synchronous double cancer) and at different times in 6
      cases (metachronous double cancer). Synchronous esophageal cancer was more common
      in cases of advanced hypopharyngeal cancer, especially Stage IV. 3. When the
      number of cancer foci, their distribution along the circumference of the
      esophagus, and the extent of tumor spread in the esophagus were investigated,
      multiple and localized foci smaller than 1 cm were found to be more common in
      synchronous cancer, and solitary foci were more common in metachronous cancer. 4.
      The second primary esophageal cancer often occupied the Im or Ei area, and in
      metachronous double cancer, it was often localized in the middle and/or inferior
      segment of the esophagus. 5. In 60% of cases of synchronous double cancer, the
      esophageal cancer was confined to the mucosa. The esophageal cancer was early
      stage in 86.7% of cases of synchronous double cancer. These findings allow us to
      draw the following conclusions: (i) Because esophageal cancer which occurs
      synchronously with hypopharyngeal cancer tends to recur, it is suggested that a
      technique that allows complete extraction of the esophagus be selected. (ii)
      Local treatment such as endoscopic mucosal resection should be selected in
      metachronous early double cancer. (iii) Unstained areas extending along more than
      half the circumference of the esophagus and more than 3 cm in size suggest a high
      probability of the presence of cancer in this area. Adequate examination is
      needed in such cases. (iv) Screening of the upper gastrointestinal tract is
      important to detect head and neck cancer. An adequate examination schedule,
      tailored to the features of individual cases, seems essential.

PMID- 9038071
TI  - [Morphological characterization and classification of air cells in temporal bone
      by digital processing of CT images].
AB  - We determined the extent of pneumatization in the temporal bone and reconstructed
      three-dimensional structures of air cells by computer-assisted digital processing
      of high resolution CT images of the bone. We attempted morphological
      classification of temporal bone air cells by characterization of the three
      dimensional structures obtained. A total of 52 ears in 33 normal subjects (18
      males and 15 females; mean age 51 years) was examined. The volume of
      pneumatization in the temporal bone, as measured by CT, ranged from 2.08 to 20.05
      ml (mean 6.40 +/- 4.09). The morphological characteristics of air cells in the
      three-dimensional images were examined with reference to the volume of air cells
      and the direct on of their growth. The three-dimensional structures were observed
      from four directions (lateral, supralateral, anterolateral and supramedial).
      Large air cells existed plentifully in all directions. Anteriorly, air cells were
      growing in two directions; laterally and toward the petrous apex. The growth in
      the latter direction was especially marked, and this contributed to the growth in
      the medial direction. Air cells that grew anteriorly had two directions of growth
      (lateral and toward the petrous apex). The directional difference in growth
      varied with the ear. On examining the suprainferior growth, air cells that grew
      large in the anterior direction were found to grow large in the suprainferior
      direction and those that did not grow large in the anterior direction were found
      contrarily to grow poorly in the suprainferior direction. With the above
      morphological characteristics taken into consideration, morphological
      classification of air cells into five types was attempted by the volume of air
      cells and the direction of their growth.

PMID- 9038072
TI  - [Immunohistological study of infiltrating cells in nasal mucosa and nasal lavage
      fluid of perennial allergic rhinitis].
AB  - It is well known that EG2-positive cells, CD68-positive cells and other
      inflammatory cells significantly increase after antigen provocation in the nasal
      mucosa of an allergic patient. However, there are few reports of the
      immunohistological study if the infiltrating cells in nasal lavage fluid are not
      seen. In this study, the infiltrating cells in nasal mucosa as well as in nasal
      lavage fluid were immunohistologically examined by means of monoclonal antibodies
      30 minutes after the antigen provocation. Seven patients with perennial allergic
      rhinitis were challenged by an antigen disk placed on one side of the inferior
      turbinates and each nasal cavity was irrigated separately 30 minutes after the
      antigen provocation. About seven days later, these patients were operated on and
      the nasal mucosa was removed 30 minutes after the antigen provocation. No marked
      change in CD4- and CD8 positive cells in the nasal mucosa and lavage fluid was
      found after provocation. On cytospin glass slides, there was a slight increase in
      the number of CD68 (P = 0.1), EG2 (P = 0.09), and neutrophil elastase positive (P
      = 0.2) cells. A significant increase in EG2-positive cells was also seen in the
      superficial layer of the lamina propria (P < 0.05) but not in the deep layer.
      CD22 positive cells were not seen on the cytospin glass slide, whereas many
      positive cells were observed in the deep layer of the lamina propria. These
      results indicate that EG2-positive cells participate strongly in the early phase
      of the allergic response after provocation in spite of the absence of significant
      changes in CD4- and CD8 positive cells. Immunohistological evaluation of nasal
      lavage is thought to be beneficial concerning the movement of each kind of cells.
      Each kind of cell is thought to fulfill the main physiological role in the
      epithelial layer or the lamina propria in early allergic inflammation.

PMID- 9038073
TI  - [The relationship between ocular abnormalities and MRI findings in patients with
      spinocerebellar degeneration].
AB  - We studied the relationship between MRI findings and ocular abnormalities in 46
      patients with spinocerebellar degeneration. MRI was performed for all patients.
      In order to evaluate the severity of atrophy in the brainstem and cerebellum, we
      delineated the region of the pons, mesencephalic tegmentum, medulla oblongata,
      cerebellar hemisphere, and vermis on a typical section of their T1 weighted
      image. Each area or the longest diameter of each regions were measured by using a
      computed graphic analyzer. The data were compared with those of 10 normal
      subjects and the severity of atrophy in each region was quantitatively estimated.
      In all of the patients, electro-oculographic tests including gaze nystagmus,
      positional and positioning nystagmus, smooth pursuit eye movements (smooth
      pursuit), optokinetic nystagmus test (OKN), horizontal saccade test, and visual
      suppression of the caloric nystagmus test (VS test) were examined. Eight patients
      with rebound nystagmus showed more severe atrophy than those of 38 patients
      without rebound nystagmus in the cerebellar hemisphere and vermis. Nine patients
      with apogeotrophic derection changing nystagmus indicates more severe atrophy
      than those of 35 patients without it in the cerevellar hemisphere, pons,
      mesencephalic tegmentum, medulla oblongata. Twenty three patients who showed
      severe impairments of OKN, 11 patients with a burst phenomenon on VS test and 19
      patients with significantly reduced saccade velocity showed particularly severe
      pontine atrophy. A significant atrophic change in the pons and medulla oblongata
      was seen in 4 patients with severely impaired pursuit eye movements. Our finding
      that there is good correlation between ocular abnormalities and markedly atrophic
      regions on MRI support the neurophysiological findings which had been reported
      concerning the generation of ocular abnormalities in humans and animals.

PMID- 9038074
TI  - [The effect of CO2 and apnea on cochlear and middle ear blood flow in guinea
      pigs].
AB  - The effect of 10% CO2 (in air) and apnea on cochlear blood flow (CBF) and middle
      ear blood flow (MEBF), capillary vessel diameters and blood pressure (BP) were
      investigated in guinea pigs. Intravital microscopic techniques (IVM) using video
      system, and laser Doppler flowmetry (LD) were used. MEBF was measured in the
      blood vessels of the middle ear mucosa over the cochlea and CBF was measured in
      the lateral wall vessels in the second or third cochlear turn. During 10% CO2
      respiration for 10 min, the highest vessel diameter dilated about 11% in the
      middle ear and 5% in the cochlea. During 5 minutes apnea, the highest vessel
      diameter constricted about 30% in the middle ear and 5% in the cochlea. Elevation
      of PCO2 dilate blood vessels with constant PO2, but constriction of blood vessels
      as observed in extremely low PO2 range even if PCO2 was elevated. The ratio of
      the change in blood flow volume to the change in BP was obtained after the change
      in blood flow volume was calculated from blood flow velocity and blood vessel
      diameter. The mean change of ratio in MEBF was a 10% decrease with 10% CO2, 28%
      decrease with apnea in IVM. The mean change of ratio in CBF was a 44% increase
      with 10% CO2, 14% increase with apnea in IVM, 67% increase with 10% CO2, 42%
      increase with apnea, in LD. The change of CBF in LD was about 20% larger than in
      IVM. Our results showed that CBF belonging to vertebral artery system was more
      strongly maintained in association with autoregulation even under conditions of
      low PO2 or high PCO2 compared to MEBF in the external carotid artery system. It
      was suggested that blood flow behavior was significantly different between the
      middle ear and inner ear.

PMID- 9038075
TI  - [Fine needle aspiration cytology under ultrasonographic imaging for diagnosis of
      thyroid tumor].
AB  - During a 66-month period, 2849 patients with thyroid gland tumor were examined by
      fine needle aspiration cytology (FNA) under ultrasonographic imaging at Yamada
      Red Cross Hospital. Of these patients, 333 received surgical therapy and
      histological examinations were performed. FNA yielded an accuracy of 92.4%, a
      specificity of 100% and a sensitivity of 88.3%. There were 16 false-negative
      reports which were mainly considered to be due to calcified lesions, cystic
      lesion, or follicular carcinoma. Among the 188 negative cases, 24 cases (12.8%)
      proved to be positive by repeated FNA-Preoperative FNA provides cytological
      information and may assist in the determination of the operative indication. This
      approach resulted in an increased rate of surgery of thyroid malignancies among
      all thyroid gland surgeries. This method need to be improved to reduce false
      negative results and the combination of FNA diagnosis and other examination is
      necessary.

PMID- 9038076
TI  - [Effects of salicylate and quinine on cat primary auditory cortex--spontaneous
      firing rate].
AB  - The effect of salicylate and quinine on the spontaneous firing rate in the cat
      primary auditory cortex was investigated in 13 healthy cats. Spontaneous firing
      rates were calculated for each single unit. A dose of 200 mg of sodium salicylate
      per kg was administered intraperitoneally to six cats, and the findings from the
      same single unit were recorded prior to application and continuously up to, on
      average, 6 hours after application. A dose of 100 or 200 mg of quinine
      hydrochloride per kg was administered intramuscularly to seven cats, and the
      findings from the same single unit were recorded in the same manner as for the
      cats treated with sodium salicylate. Twenty one single units in salicylate
      treated cats and 29 single units in quinine-treated cats were evaluated. All
      animals treated with salicylate showed a 20-30 dB threshold shift about 2 hours
      after application and showed no recovery during the course of the investigation.
      All animals treated with quinine showed a 10-40 dB threshold shift about 1 hour
      after application and recovered during the course of the investigation. There was
      no consistent difference in overall spontaneous firing rate before and after
      application in either salicylate-treated cats or quinine treated cats. In order
      to investigate a potential different effect on units with different spontaneous
      firing rates, we divided the cats into two groups, a high-firing rate group (pre
      application firing rate > 1 spike/s) and a low firing rate group (pre-application
      firing rate < 1 spike/s). A significant decrease in the high-firing rate group (p
      < 0.05) and a significant increase in the low firing rate (p < 0.01) were
      observed in salicylate-treated cats. The same tendencies were observed in quinine
      treated cats, but only the difference in the low firing rate group was
      significant (p < 0.05). The difference in the high-firing rate group was close to
      the significant level (p = 0.055). These changes in spontaneous firing rates in
      cat primary auditory cortex may be related to the generation of tinnitus.

PMID- 9038077
TI  - [Biological behavior of hypopharyngeal carcinoma].
AB  - Hypopharyngeal squamous cell carcinomas (HPC) has an extremely poor prognosis.
      Characteristics of cell lines of head and neck squamous cell carcinomas including
      HPC were studied by various methods, e.g., chemosensitivity test and the
      immunohistochemistry staining method, to determine whether this poor prognosis is
      due to the biological behavior of this cancer. An HPC cell line was found to be
      resistant to anti tumor drugs, i.e., PEP, MTX and CPM and moderately sensitive to
      CDDP, 5-FU and ADM. Thermoresistance to hyperthermatic treatment and weak
      expression of ICAM-1 on the HPC cell line were observed. DNA synthesis by the HPC
      cell line was induced by stimulation with a low concentration of EGF and the
      amount of EGFR on these HPC cells was very high. In addition, cyclinD1
      overexpression was found in the HPC cell line. Based on the above findings,
      further analysis of hypopharyngeal carcinoma cells and the development of a new
      treatment modality to control tumor growth and metastatic factors influencing the
      poor outcome are necessary to improve the prognosis of this cancer.

PMID- 9038078
TI  - Current good manufacturing practice: proposed revision of certain requirements
      for finished pharmaceuticals; proposed rule, May 3, 1996 (61 FR 20103), [Docket
      No. 95N-0362]. Parenteral Drug Association.

PMID- 9038079
TI  - Use of the green fluorescent protein to rapidly assess viability of E. coli in
      preserved solutions.
AB  - E. coli strain HB101 was genetically engineered to a fluorescent phenotype by
      transformation with a plasmid containing complementary DNA for a green
      fluorescent protein. The level of fluorescence in the transformed strain was
      directly proportional to the number of viable cells. There was a rapid decrease
      in fluorescence when transformed cells were inoculated into lamivudine solutions
      containing ten different preservative formulations. The decrease in fluorescence
      correlated to a decrease in the number of viable cells, allowing the relative
      antimicrobial properties of each solution to be compared. This methods provides a
      simple, rapid (< 2 min/assay), and accurate means of determining the effects of
      antimicrobial solutions on the viability of E. coli.

PMID- 9038080
TI  - Parenteral formulation of Flavopiridol (NSC-649890).
AB  - Flavopiridol [5,7-dihydroxy-8-(4-N-methyl-2-hydroxypyridyl)-6' -chloroflavone
      hydrochloride] is a flavonoid with weak electrolyte properties and an intrinsic
      aqueous solubility of 0.024 mg/mL. Neither cosolvency complexation, nor pH
      control alone can produce an acceptable 10 mg/mL formulation that will not
      precipitate when diluted with blood. However, a combination of buffer and
      cyclodextrin or buffer and cosolvent can produce an acceptable 10 mg/mL
      formulation. In this paper, Flavopiridol is shown to be stable for at least one
      year in 30% hydroxypropyl beta-cyclodextrin/0.1 M citrate buffer (4.52). This
      formulation does not precipitate for at least one hour upon dilution with
      Sorensen's phosphate buffer pH 7.4.

PMID- 9038081
TI  - Enhancing effect of non-ionic surfactant on the inactivation of
      lipopolysaccharide by steam-heat treatment I.
AB  - Polyoxyethylene (20) sorbitan mono-fatty acid esters strongly enhanced the
      inactivation of lipopolysaccharide (LPS) by steam-heat treatment at 121 degrees
      C, as assayed by using the Limulus amebocyte lysate (LAL) and the pyrogen test.
      In an aqueous solution containing 0.1% surfactant, the decrease of LPS (1
      microgram/ml) from E. coli 055:B5 at 121 degrees C followed first-order kinetics.
      Based on the LAL assay, 0.1% surfactant was essential to achieve 3-log cycle
      reduction of LPS with concomitant loss of pyrogenicity by steam-heat treatment
      for 20 min at 121 degrees C. Steam-heat treatment for 20 min at 121 degrees C in
      the absence of surfactant was insufficient to achieve depyrogenation.
      Polyoxyethylene (9) lauryl ether and decaglycerin mono-laurate similarly enhanced
      depyrogenation by steam-heat treatment. The effects of all the surfactants were
      concentration-dependent for all of the six kinds of LPS examined.

PMID- 9038082
TI  - Stabilization of teniposide in aqueous mixtures of detergent-phospholipid.
AB  - Teniposide-containing mixed micelles and liposomes consisting of detergent and
      phospholipid were investigated and compared for their teniposide latency as
      functions of the mixed micellar preparation method, stabilizers, type of
      detergent,lipid composition and serum proteins after storage at 10 degrees C, and
      23 degrees C, and 45 degrees C or/and freezing and freeze-drying. There was no
      significant difference in teniposide loss from liposomes obtained using different
      micellar preparation methods. Sugars, dextrose or sorbitol, had no effect on
      teniposide loss from liposome but stabilized teniposide micelles. Glutamic acid
      had no effect on teniposide loss from micelles but increased the loss from
      liposomes. The presence of cholesterol in bile salt-egg PC micelles had little
      effect on teniposide loss at 10 degrees C but generally increased it at 23
      degrees C, and 45 degrees C, while bile salt-egg PC-cholesterol (9:9:1) liposomes
      were more stable than bile salt-egg PC liposomes. In contrast, teniposide loss
      from bile salt-egg PC-egg PE (2:1:1) liposomes or bile salt-egg PC-egg PA
      (16:15:1) micelles and liposomes increased remarkably, probably due to the
      surface charge and/or the destabilization of PC bilayer. However, bile salt-egg
      PC-soy PC (2:1:1) micelles and liposomes lost less amounts of teniposide under
      the same storage conditions. Further, the stability of teniposide was greatly
      increased by neutral detergents (e.g., CHAPS or octylglucoside). The loss of
      teniposide from CHAPS- or octylglucoside-egg PC micelles and liposomes after six
      months' storage at the ambient temperature were approximately 16% and 10%,
      respectively. Teniposide-micelles and liposomes, prepared in the presence of
      serum or serum protein, were more stable than CHAPS- or octylglucoside-egg PC
      liposomes. Teniposide was physically stable for at least 12 months when micelles
      were stored as the frozen or freeze-dried state. This result suggested that long
      term storage for teniposide in neutral detergent-egg PC-soy PC micelles may be
      feasible in the presence of serum proteins.

PMID- 9038083
TI  - Antibody mediated lung targeting of long-circulating emulsions.
AB  - Monoclonal antibody 34A, which specifically binds to a surface glycoprotein
      (thrombomodulin) of the pulmonary endothelial cell surface in mice, has been
      conjugated to the surface of long-circulating emulsions composed of Castor oil,
      phosphatidylcholine and polyethylene glycol coupled to distearoylphosphatidyl
      ethanolamine. These antibody-containing emulsions were found capable of binding
      to the lung when injected into mice through the tail vein. The level of lung
      accumulation of these emulsions depends on the amount of antibodies conjugated to
      the surface of the emulsions. With an input antibody to lipid ratio of 2:1 (w/w),
      30% injected emulsions were found in the lung 30 minutes after administration.
      Such high level accumulation can be blocked by co-administration of free 34A
      antibody, indicating that the binding is specific and 34A antibody mediated.
      Kinetic studies showed that emulsion targeting to the lung was very rapid. Five
      minutes after tail vein injection, the total amount of emulsion found in the lung
      was the highest among the time points examined, indicating the completion of lung
      binding. However, about 50% of the initially bound emulsions remained bound for
      more than 4 hours. These results indicate that the targeted drug delivery using
      oil-in-water emulsions could be very useful to enhance the therapeutic efficacy
      of lipophilic drugs.

PMID- 9038085
TI  - The FDA-483: history and use in drug inspections.

PMID- 9038084
TI  - Current approaches in leak testing pharmaceutical packages.

PMID- 9038086
TI  - Microbial barrier assessment of Tyvek stopper packaging for rubber closures.
AB  - Two types of Tyvek and high density polyethylene or polypropylene packaging used
      for sterilization of rubber closures were evaluated for Microbial Barrier
      properties. The packaging evaluated was "Ready to Sterilize" (1) stoppers and a
      second test package (Test 2) which was designated as appropriate for a clean
      room, filled with washed and siliconized stoppers and then heat sealed. Each type
      of packaging was subjected to three different sterilization temperatures (125
      degrees C, 128 degrees C and 131 degrees C) in a production sterilizer (15-18
      psi). Following sterilization, a microbial barrier assessment was performed,
      using Bacillus subtilis niger (ATCC 9372), to determine whether the packaging
      could maintain a sterile barrier following sterilization. Results of the testing
      indicated that a microbial barrier was maintained for products in "Ready to
      Sterilize" packages at 125 degrees C and 128 degrees C. For products sterilized
      in the Test 2 container a microbial barrier could not be maintained at 128
      degrees C, and no further testing was performed. Following sterilization at 131
      degrees C physical defects were noted for the "Ready to Sterilize" bag and a
      microbial barrier could not be maintained.

PMID- 9038087
TI  - Analysis and evaluation of filter cartridge extractables for validation in
      pharmaceutical downstream processing.
AB  - This paper describes a comprehensive approach for the extractables analysis of
      filter cartridges used in pharmaceutical production processes. For the extraction
      of the cartridges, two model solvents (water and ethanol) and worst case
      conditions are used. The extracts of 8 cartridges from various filter
      manufacturers are analysed both in the original and the concentrated form to gain
      data about the high and low concentrated contaminants, implementing standard
      analytical techniques such as GC-MS, RP-HPLC, GPC and FT-IR. Degradation products
      and additives of the filter cartridge polymers are found to be the source of most
      of the extracted compounds. The concentrations of extractables are determined in
      the range of ppm to ppb per cartridge under the applied extraction conditions.
      The effect of rinsing the cartridges prior to use was studied, showing a
      reduction of the extractables even after small flush volumes.

PMID- 9038089
TI  - Trouble in paradise: physicians in the managed care era.

PMID- 9038088
TI  - Process simulation testing for aseptically filled products. Parenteral Drug
      Association.

PMID- 9038090
TI  - Soranus's notion of sympathy and the modern patient: challenges for medical
      methodology.

PMID- 9038091
TI  - Medical practice: past, present, future.

PMID- 9038092
TI  - Border crossings in medical education.

PMID- 9038093
TI  - The human toll of managed care.

PMID- 9038094
TI  - Emily post has surgery.

PMID- 9038095
TI  - The architecture of conflict.

PMID- 9038096
TI  - Altruism--a flawed morality?

PMID- 9038097
TI  - Altruism--a flawed morality?

PMID- 9038098
TI  - Training professionals for the new public health.

PMID- 9038099
TI  - Shigellosis in Israel--update 1995.
AB  - INTRODUCTION: The incidence of shigellosis in Israel was fairly stable until
      around 1974, when it gradually began to increase to a peak in 1985. This was
      accompanied by a shift in the maximum incidence in the Jewish population from the
      age group < 1 to 1-4 years. AIM: To update the epidemiology of shigellosis in
      Israel 1986-1995. METHODS: Only laboratory-confirmed cases of shigellosis in the
      civilian population were analyzed. Data were obtained from the weekly reports of
      the subdistricts. Antibiotic sensitivity data were obtained from several
      hospitals and the General Workers' Sick Fund laboratories in Jerusalem, Haifa,
      and Tel Aviv. RESULTS: From 1986 to 1991, shigellosis incidence per 100,000
      decreased by about 50%, and the decrease occurred mainly in the Jewish
      population. Several regional outbreaks in 1992 reversed this decline, but by
      1995, the incidence was similar to that observed prior to 1974. The disease still
      occurs mainly in the summer, with an occasional winter outbreak. Higher incidence
      rates occurred in the northern subdistricts. The peak incidence in the non-Jewish
      population moved from the < 1-year-olds to the 1-4 year-old group, similar to the
      pattern in the Jewish population in 1970. In 1991, for the first time, the rate
      in the age group 5-9 years among non-Jews exceeded that of those < 1 year old.
      Marked decreases in sensitivity to several antibiotics were found in peripheral
      and hospital laboratories. An increase in the sensitivity to tetracycline was
      noted since 1991. Case fatality rates remain low, with a mean of 0.05% for the
      decade of the 1980s. CONCLUSIONS: Shigellosis remains a highly endemic disease in
      Israel, but changes in the age-related peak incidence indicate that the pattern
      of spread is becoming more similar to other developed countries.

PMID- 9038100
TI  - Isolation of Mhc class I cDNAs from the axolotl Ambystoma mexicanum.
AB  - Class I major histocompatibility complex (Mhc) cDNA clones were isolated from
      axolotl mRNA by polymerase chain reaction (PCR) and by screening a cDNA phage
      library. The nucleotide and predicted amino acid sequences show definite
      similarities to the Mhc class Ialpha molecules of higher vertebrates. Most of the
      amino acids in the peptide binding region that dock peptides at their N and C
      termini in mammals are conserved. Several amino acids considered to be important
      for the interaction of beta2-microglobulin with the Mhc alpha chain are also
      conserved in the axolotl sequence. The fact that axolotl class I A cDNAs are
      ubiquitously expressed and highly polymorphic in the alpha1 and alpha2 domains
      suggests the classical nature of axolotl class I A genes.

PMID- 9038101
TI  - AICL: a new activation-induced antigen encoded by the human NK gene complex.
AB  - The NK gene complex on mouse chromosome 6 and its human homologue on chromosome
      12 encode type II transmembrane proteins with a C-type lectin domain which
      trigger or inhibit target cell lysis by NK cells (NKR-P1, Ly49, NKG2, CD94) or
      function as cellular activators of various hematopoietic cells (CD69). We herein
      report the cDNA cloning of a new molecule, designated activation-induced C-type
      lectin (AICL), whose gene maps to the human NK gene complex proximal to the CD69
      gene. AICL is a 149-amino acid (aa) polypeptide with a short cytoplasmic part of
      seven aa and a C-type lectin domain separated from the transmembrane region by
      only nine aa. The highest sequence similarity is found to the C-type lectin
      domains of CD69 and the chicken lectin 17.5. The presence of AICL transcripts in
      different cell types of hematopoietic origin, a rapid increase of gene
      transcription during lymphocyte activation, and a short half-life of the mRNA
      characterize AICL as a new, broadly expressed activation antigen.

PMID- 9038102
TI  - IgG rheumatoid factors isolated by the surface-displaying phage library
      technique.
AB  - Our analysis of IgG rheumatoid factors (RFs) from three patients with rheumatoid
      arthritis (RA) revealed that most contained significant numbers of skewed
      mutations per V region, suggesting that these RFs arose from antigen-driven
      responses. To further study IgG RFs in RA, we used pComb3 vector to construct an
      IgG1,lambda combinatorial antibody library from a synovial fluid sample. After
      panning against human IgG, Fab fragments from 71/96 phage clones bound to Fc
      coated wells. Sequence analysis of 20 randomly chosen Fc-binders showed that 17
      (85%) clones had identical heavy (H) and light (L) chain V regions, represented
      by Humha311 and Humla211, respectively. Of the remaining three clones, two had
      the same Humla211 L chain, but each with a different H chain V region. All the
      putative germline V genes for these RFs also encode RF in RA patients. However,
      none of these RF V regions are similar to those of the two IgG RFs derived by the
      hybridoma technique from the same synovial fluid. The Humha311 H chain has two
      frameshifts: a one-base insertion upstream of the JH region and a four-base
      deletion near the end of the CH1 region, resulting in a mainly unconventional
      amino acid sequence in the CH1 region. In the future, it will be important to
      study the presence of IgG molecules with such unconventional CH1 amino acid
      sequences, and the effects of these amino acid sequences on the structures and
      immunological properties of the IgG molecules.

PMID- 9038103
TI  - Mutation in splicing consensus sequences causes lack of TCR membrane expression
      due to exon excision.
AB  - T-cell antigen receptor (TCR) membrane-negative T-cell mutants can be divided
      into two groups: 1) those which lack one of the six TCR polypeptides and 2) those
      which contain a mutated TCR chain. The present experiments reveal a new mechanism
      for the development of TCR membrane-negative T-cell variants: mutations in
      splicing consensus motifs causing excision or misreading of an entire exon (exon
      3 of the TCRAC or TCRBC genes). C27.15 cells transcribe a TCR alpha chain
      consisting of TCRAVJCexon1Cexon2-encoded amino acids plus six new amino acids.
      The assembly defect seems to be that the truncated alpha chain does not interact
      with CD3 delta molecules; consequently, no TCR alphabeta/CD3
      deltaepsilongammaepsilon complexes are formed. E6.E12 cells transcribe a TCR beta
      chain composed of TCRBVDJCexon1Cexon2-encoded amino acids plus twenty-seven new
      amino acids, which seem not to form a transmembrane region. The truncated beta
      chain does associate with CD3 gammaepsilon heterodimers, yet no TCR alphabeta/CD3
      deltaepsilongammaepsilon complexes are made. This may be due either to low
      assembly of TCR beta/CD3 gammaepsilon trimers or to lack of access of the mutated
      TCR beta/CD3 gammaepsilon trimers to the TCR alpha/CD3 deltaepsilon compartment
      in the endoplasmic reticulum.

PMID- 9038104
TI  - Mutations in the MHC class I-like candidate gene for hemochromatosis in French
      patients.
AB  - A candidate gene for hemochromatosis has recently been localized on the short arm
      of chromosome 6, about 4 megabases telomeric to the major histocompatibility
      complex. It encodes a protein that exhibits significant similarity to the HLA
      class I molecules and can be provisionally designated HLA-hc. Genotype analysis
      of 94 hemochromatosis patients living in France and a similar number of controls
      confirms that the disease is strongly associated with homozygosity at nucleotide
      845 (72% of the patients and none of the controls carry two copies of the 845A
      variant). The data are consistent with hemochromatosis being a heterogeneous
      disease: about 79% of the cases in this sample would be caused by a defect in HLA
      hc and 21% by an unrelated mechanism. A second variant (187 G) enriched on
      patient chromosomes that do not carry the 845A mutation might influence the
      affinity of a ligand for HLA-hc; the exact nature of this ligand remains to be
      discovered. The 845A variant is the best genetic marker for the disease
      identified to date, and the detection of 845A homozygosity should now permit
      diagnosis of a readily curable disease and the prevention of sometimes deadly
      complications in at least 72% of the patients.

PMID- 9038105
TI  - The helper T-cell repertoire of mice expressing class II major histocompatibility
      complex beta chains in the absence of alpha chains.
AB  - Mutant mice generated by disrupting the H2-Aab major histocompatibility complex
      (Mhc) gene are demonstrated here to express Abetab chains in the absence of alpha
      chains. These mice possess a CD4(+) helper T cell (Th) repertoire that uses
      predominantly the Vbeta7 T-cell antigen receptor (Tcr) segment for recognition of
      any protein antigen presented by the alpha-free Abeta molecule. As an
      alloantigen, the Aalpha-free Abeta molecule is recognized very poorly by T cells
      from a series of class II disparate mouse strains, indicating that it is grossly
      different from normal alpha/beta heterodimers. Indeed, molecular modeling
      suggests a beta/beta homodimer arrangement with an altered geometry of the Tcr
      contact area. Interestingly, the mutant mice exhibit normal alloreactivity,
      without a restricted Vbeta usage, toward a series of foreign alpha/beta class II
      heterodimers, although their T cells developed in the absence of such
      heterodimers. Thus, the complementarity of Tcr to normal alpha/beta heterodimers,
      and thereby also alloreactivity, appears to be an ontogeny independent (i. e.,
      germline-encoded) feature.

PMID- 9038106
TI  - Recombination activating gene-1 of the opossum Monodelphis domestica.

PMID- 9038107
TI  - Functional expression of the IGKV A18b gene and its idiotypic cross-reactivity
      with the A2 variable region.

PMID- 9038109
TI  - Systemic arterial air embolism and tension pneumothorax: two complications of
      transthoracic percutaneous thin-needle biopsy in the same patient.
AB  - Systemic arterial air embolism and tension pneumothorax are two rare and severe
      complications of transthoracic fine-needle biopsy. We report on a patient who
      developed both complications during the same procedure and recovered successfully
      after resuscitation and hyperbaric oxygen therapy. Favourable outcome of systemic
      air arterial embolism has been reported infrequently in the literature. In our
      case tension pneumothorax may have influenced favourably the course of the
      illness due to collapse of distal airways and the reduction of the venous return
      to the heart from the affected side.

PMID- 9038108
TI  - Staging intrathoracic non-small-cell lung cancer.
AB  - This article outlines the ability of imaging techniques to stage intrathoracic
      non-small-cell lung cancer, particularly the extent of primary tumour (T stage),
      and the presence of nodal metastases (N stage). The detection of hilar and
      mediastinal lymph-node metastases by CT is covered initially, followed by an
      appraisal of MRI and radionuclide imaging techniques. Finally, the evaluation of
      mediastinal and chest-wall invasion by CT and MRI is described, and note is made
      of developing applications of ultrasound and endosonography. Computed tomography
      remains the standard technique, but its limitations are discussed, as is the
      value of other complementary imaging techniques.

PMID- 9038110
TI  - Multiple pulmonary artery pseudoaneurysms: intrasaccular embolization.
AB  - We report the case of a 32-year-old female presenting with two pulmonary artery
      false aneurysms of mycotic origin. Considering the natural history and potential
      complications, we treated the patient by intrasaccular embolization with steel
      coils. No complication occurred.

PMID- 9038111
TI  - Imaging of avascular necrosis of bone.
AB  - The etiology of avascular necrosis (AVN) is multifactorial. Independent of its
      etiology and localization it shows typical pathologies and radiological images.
      In the early stages localized subchondral edema is characteristic. In 50 % of all
      cases accompanying joint effusion may be found. Due to necrosis of the cells of
      bone marrow and bone fibrovascular, reactions with hyperemia can be delineated.
      These reactions allow us to visualize necrosis indirectly. The best imaging
      methods are MRI and, to a lesser extent, bone scintigraphy. In later stages
      calcification as well as new bone formation and microfractures are typically
      demonstrated and visualized best with plain X-rays and CT. Why reparations in
      many cases, particularly in the hip, are incomplete and may stop in any stage is
      unknown. Over years clinically complete silent AVNs are not an uncommon finding.
      Prognosis depends on the localization and size of the AVN. The number of repair
      mechanisms is best outlined with contrast-enhanced MRI and return of fatty
      marrow.

PMID- 9038112
TI  - Rapid prototyping (stereolithography) in the management of intra-articular
      calcaneal fractures.
AB  - The purpose of this study was to evaluate and compare the diagnostic performance
      of stereolithography vs workstation-based three-dimensional (3D) reformations in
      intra-articular calcaneal fractures. A total of 30 intra-articular calcaneal
      fractures were examined using standard radiographs, coronal CT scans, and 2D and
      3D reformations. The CT data were transferred to an outside institution, and
      stereolithograms were produced from photopolymer resin employing a laser beam
      system. 3D reformations and stereolithograms were analyzed in a blinded fashion
      by two staff radiologists. Receiver-operating-characteristic (ROC) curves were
      obtained for six clinically significant fracture components. Standard
      radiographs, coronal CT scans, and 2D reformations served as the standard of
      reference. The area under the ROC curves for 3D reformations and stereolithograms
      were 1.0 and 0.98 for abnormal tuber angles, 0.91 and 0.91 for anterior and
      middle talo-calcaneal joint involvement, 0. 90 and 0.95 for involvement of the
      posterior talo-calcaneal joint, 0. 65 and 0.78 for the presence of a lateral
      bulge, 0.80 and 0.81 for the involvement of the calcaneocuboidal joint, and 0.62
      and 0.67 for the presence of a "tongue-type" fracture. No statistically
      significant difference was demonstrated for the two methods (Wilcoxon signed-rank
      test, p = 0.138). Based on our results stereolithograms did not prove to be
      statistically superior to workstation-based 3D reformations. Stereolithograms may
      still be useful for teaching purposes and for surgical planning at a thinking
      efficacy level.

PMID- 9038113
TI  - Diagnosis of rotator cuff lesions: comparison of US and MRI on 38 joint
      specimens.
AB  - An experimental study was performed on cadaveric joint specimens of the shoulder
      to determine the accuracy of US and MRI in diagnosis of abnormalities of the
      rotator cuff. The value of different morphological criteria was evaluated for
      discrimination of degeneration as well as partial and complete disruption. A
      total of 38 surgically exposed specimens of the shoulder joint were examined by
      US, MRI and pathological methods visualising the tendons of the rotator cuff in
      same axial and longitudinal orientations. The three imaging modalities were
      reviewed separately by experienced examiners, respectively, who were blind to
      other results. Evaluation criteria consisted of signs of shape (thinning,
      thickening, discontinuity and absence of rotator cuff) and structure (changes in
      echogenicity in US, increased signal intensity in MRI, tissue changes in
      pathology). Findings in US and MRI were finally compared with pathology to assess
      sensitivity and specificity. Pathology demonstrated 4 full-thickness tears, 6
      partial-thickness tears, 16 cases with degeneration and 12 normal rotator cuffs.
      Ultrasound showed pathological signs in all abnormal cuffs, and one MRI report
      was false negative. Specificity was 67 % in US (4 of 12 cases were false
      positive) and 100 % in MRI (no abnormal findings in healthy tendons).
      Discrimination of different pathological disorders of the rotator cuff was
      reduced in both methods. Using US only 10 of 16 cases of degeneration, 2 of 6
      partial tears and 3 of 4 complete tears were correctly defined. Using MRI 13 of
      16 degenerations, 3 of 6 partial tears and 3 of 4 complete tears were detected.
      The MRI technique failed to visualise intratendinous calcifications in all 3
      cases. We conclude that MRI and US are both sensitive in detection of
      abnormalities of the rotator cuff. Ultrasound should be the primary diagnostic
      method in screening of shoulder pain because it is economic and fast. The MRI
      technique should be used secondary because it provides more information about
      extent of tendons and has lower risk of artefacts.

PMID- 9038114
TI  - Magnetic resonance imaging of localized giant cell tumour of the tendon sheath
      (MRI of localized GCTTS).
AB  - The objective of this study was to evaluate the appearance of localized giant
      cell tumour of the tendon sheath (GCTTS) on unenhanced and Gd-enhanced MR images.
      MR images of 13 histologically proven cases of localized GCTTS were evaluated for
      mean size, location, homogeneity and signal intensity (SI) on both T1- and T2
      weighted images, and enhancement pattern. All lesions except 1 affected young
      adults. On T1- and T2-weighted images, lesions showed predominantly low SI equal
      to or slightly higher than skeletal muscle. On Gd-enhanced T1-weighted images,
      strong homogeneous enhancement was seen. These findings reflect the underlying
      histological composition of the lesion; haemosiderin deposition in xanthoma
      cells, shortening T2-relaxation time, and abundant collagenous proliferation are
      responsible for low SI on T1- and T2-weighted images. Strong homogeneous
      enhancement originates from numerous proliferative capillaries in the collagenous
      stroma. We conclude that these characteristic MR features, together with clinical
      information, are a valuable diagnostic tool in offering a correct preoperative
      diagnosis.

PMID- 9038115
TI  - Congenital synchondroses in the ischial bones.
AB  - In this paper, a 39-year-old woman is presented with congenital, symmetrically
      bilateral synchondroses in the bodies of the ischial bones, which presumably
      occurred due to extension of two separate primary ossification centers which
      failed to fuse, instead of a usual single primary ossification center. To the
      best of the author's knowledge, such an anomaly has not been reported previously
      in the ischial bones. The apparent clinical significance of these synchondroses
      was development of degenerative changes about them, which was associated with
      moderate hip pain in the absence of degenerative hip-joint disease.

PMID- 9038116
TI  - Mammographic pattern due to residual Lipiodol after galactography.
AB  - The purpose of this pictorial essay is to describe the different mammographic
      aspects of residual Lipiodol ultra fluid (LUF) after galactography, and to define
      some specific patterns, because it may in some cases mimic microcalcifications
      and give diagnostic problems. The mammograms of 14 patients, aged 32-63 years,
      presenting LUF residues related to previous galactography, were analyzed
      retrospectively. In 12 cases the diagnosis was easy because the patients
      presented a typical pattern on mammography and came with their initial
      galactography. In 2 cases the diagnosis was more difficult because the patients
      did not remember the previous injection and the progressive resorption mimicked
      perfectly intraductal calcification. Benign duct ectasia with inflammatory
      reaction to foreign bodies were found in 3 cases in which surgery was performed.
      Lipiodol ultra fluid is no longer used for galactography, but it may persist in
      breast ducts or cysts for years and seems to still be used in some countries.
      There are in most cases specific signs enabling the diagnosis.

PMID- 9038117
TI  - Postmeningitic labyrinthine ossification primarily affecting the semicircular
      canals.
AB  - In a series of six cochlear-implant candidates, including three small children,
      labyrinthine ossification in various stages of development was observed at CT. In
      four of the candidates the ossifying process was more advanced in the
      semicircular canals than in the cochleae, and in two equally distributed. The
      ossifying process developed during a period of 4-5 months in two of the children.
      Asymmetry of its extension was found in four patients. The causative organisms
      were Hemophilus influenzae and Streptococcus pneumoniae. The radiologic
      assessment of cochlear-implant candidates should include the semicircular canals
      where the ossification may start, and herald the development of cochlear
      ossification.

PMID- 9038118
TI  - Estimation of thyroid gland volume by spiral computed tomography.
AB  - The objective of this study was to test the accuracy of CT for the estimation of
      the volume of enlarged thyroid glands. An unenhanced spiral CT scan of neck and
      upper mediastinum was obtained in 36 patients with an enlarged thyroid gland. By
      manual segmentation the surface of the thyroid gland on 5-mm-thick slices was
      calculated; these surfaces were multiplied by the slice interval (10 mm) and
      summated to obtain the volume of the gland. All patients underwent a total or
      subtotal thyroidectomy. 1 cm3 of thyroid gland tissue was considered to weigh 1
      g. A good correlation was found between the volume estimated by CT and the weight
      at pathological examination of the resected gland (r = 0.98, p < 0.001), with a
      mean difference of + 12 % (range: + 57.3 to -13.9 %). The volume calculation is
      reproducible among different observers (r = 0.99, p < 0.01). Computed tomography
      allows an easy, reliable and reproducible volume determination of enlarged
      thyroid glands.

PMID- 9038119
TI  - Has ultrasonography a role in screening for prostatic cancer?
AB  - Prostate specific antigen (PSA) is widely used as the first line test for the
      diagnosis of prostate cancer in asymptomatic men. The role of transrectal
      ultrasound is now predominantly accepted as a means of accurate biopsy of the
      prostate, but there is confusion about the best biopsy protocols for the
      diagnosis of prostate cancer. Optimum diagnosis of prostate cancer is obtained
      using a combination of digital palpation of the prostate, serum PSA measurements
      and transrectal sonography. The role of colour Doppler imaging in the diagnosis
      of prostate cancer is still under assessment.

PMID- 9038120
TI  - Renal cell carcinoma of clear type: correlation of CT features with tumor size,
      architectural patterns, and pathologic staging.
AB  - The purpose of this study was to report the CT findings of renal cell carcinoma
      of clear type (RCCCT) and to determine if there are characteristic morphologic
      features in RCCCT with respect to tumor size, architectural patterns, and
      pathologic stage. The CT scans of 35 patients with RCCCT were reviewed
      retrospectively. The CT findings (tumor size, attenuation patterns, presence of
      calcifications, encapsulation, margins of neoplasms, venous involvement by
      neoplasms) were correlated with tumor size, architectural patterns, and
      pathologic staging. Of the 35 neoplasms, 28 (80 %) were solid, 4 (11 %) were
      papillary, and 3 (9 %) were cystic. Complete encapsulation was more frequent in
      lower pathologic stages (40 % in stages 1 and 2 vs 0 % in stages 3 and 4; p <
      0.05). Venous involvement was less frequent with completely encapsulated
      neoplasms (0 of 10, 0 %) than with incompletely or nonencapsulated neoplasms (8
      of 25, 32 %; p < 0.05). Encapsulated RCCCT are more likely to have lower
      pathologic stage. Nonencapsulated neoplasms are more likely to have a higher
      pathologic stage.

PMID- 9038121
TI  - Low-field MRI pelvimetry.
AB  - The purpose of this study was to evaluate the usefulness of low-field MRI
      pelvimetry and to correlate the results with X-ray pelvimetry. A total of 19
      women underwent low-field MRI pelvimetry. Mediosagittal and transverse planes
      were used to measure the diameters of the minor pelvic cavity. Correlations
      between MRI and X-ray pelvimetry were 0.96 for the sagittal inlet, 0.94 for the
      sagittal outlet, 0.93 for the transverse diameter (diameter transversa, DT) and
      0.94 for the bispinous distance (interspinous distance, IS). The repeatability of
      the measurements was good. For fetuses with cephalic presentation it was also
      possible to determine the biparietal diameter (BPD). Low-field MRI pelvimetry was
      well accepted by the patients. The scanning time was less than 6 min, which is
      comparable with the time of X-ray examination with two planes. Magnetic resonance
      imaging provides a reliable method to image pelvic structures and soft tissue
      without ionizing radiation.

PMID- 9038122
TI  - Communicating bicornuate uterus with double cervix and septate vagina: an
      uncommon malformation diagnosed with MR imaging.
AB  - We report a case of communicating uterus diagnosed with MRI. These uterine
      malformations are characterized by a communicating tract between two separate
      uterocervical cavities, which is usually detected with hysterosalpingography
      performed for a suspected uterine malformation. In our patient MRI was performed
      after the clinical finding of a double cervix and a vaginal septum and
      demonstrated two separate uterine cavities, each of them with its own junctional
      area, and an isthmian transverse communicating tract with endometrial tissue
      inside, which helped make the diagnosis of a type-4 a communicating uterus
      according to Toaff.

PMID- 9038123
TI  - Non-Hodgkin's lymphoma of the prostate in a young male.
AB  - A case of non-Hodgkin's lymphoma (NHL) involving the prostate and the urinary
      bladder in a 24-year-old male is reported. Although none of the currently
      available imaging modalities is specific for the diagnosis of NHL of the
      prostate, this diagnosis must be considered because of its amenability to
      treatment. The heterogeneity of the mass at CT and MRI might be suggestive of
      high-grade NHL. The patient was treated with intensive combination chemotherapy.

PMID- 9038124
TI  - Pancreatic metastases: CT assessment.
AB  - We report the CT appearance of pancreatic metastases and describe their features
      in relation to the originating primary tumor. We also discuss some limitations in
      their differential diagnosis and report some theories explaining the pathogenesis
      of their occurrence. A total of 20 cases (9 males and 11 females) of pancreatic
      metastases were diagnosed at staging or follow-up of oncologic patients. All
      patients were evaluated with CT before and after contrast medium administration
      and had subsequent pathologic confirmation. In 1 case metastases were located
      solely in the pancreas; in 6 there was only another metastatic location, and in
      the remaining 13 there was diffuse spread throughout the body. Two of our
      patients exhibited a multinodular metastatic involvement of the pancreas, 11 had
      a solitary nodule or mass, and the remaining 7 had a diffusely enlarged pancreas,
      without any signs of focal disease. All but one of the solitary lesions measured
      more than 4 cm. In 2 cases a metachronous malignancy was detected at follow-up.
      Primary malignancies were located: 6 in the lungs, 2 on the skin (melanomas), 3
      in breasts, 2 in the ovaries, 3 in the colon, 1 in the stomach, 2 in the kidney,
      and 1 the thyroid. Our findings confirm the existence of three patterns of
      metastatization to the pancreas: large solitary masses, multinodular lesions, and
      diffuse enlargement of the pancreas without focal signs at CT. In contrast to
      other studies, the large solitary lesion was our most frequent encounter,
      therefore making differential diagnosis vs primary cancer difficult. Metastases
      tended to repeat the imaging pattern of the primary. Nevertheless, we wrongly
      diagnosed pancreatitis due to a small nondetected metastasis, pseudo-cystic mass
      as a mucinous cystadenocarcinoma, conglomerate of peripancreatic lymph nodes, and
      a solitary pancreatic mass diagnosed as primary pancreatic cancer. Thus, when
      faced with a solitary pancreatic lesion at follow-up, histologic diagnosis is
      strongly recommended. In 2 cases changes in aspect and size were related to
      therapy.

PMID- 9038125
TI  - Determination of normal splenic volume on computed tomography in relation to age,
      gender and body habitus.
AB  - The purpose of our study was to examine variations in normal splenic size in
      relation to age, gender and body habitus in vivo, and to determine normative data
      for splenic volume on CT. The width (W), length (L), thickness (Th), cross
      sectional areas and volume (Vol) of the spleen were obtained from abdominal CT
      examinations of 140 patients who underwent CT for indications unrelated to
      splenic disease. Splenic volume did not vary significantly (-0.04 < r < 0.05, p >
      0.10) with the patient's age, gender, height, weight, body mass index or the
      diameter of the first lumbar vertebra, the latter considered as representative of
      body habitus on CT. The mean value of the measured splenic volume (S Vol) was
      214.6 cm3 with a range from 107.2 to 314.5 cm3. S Vol correlated well with all
      the linear and the maximal cross-sectional area measurements and could be
      calculated using the formula: S Vol = 30 + 0.58 (W x L x Th.). Employing the same
      formula splenic volume was reliably assessed in 47 patients with clinically
      evident splenomegaly. Quantitative assessment of splenic volume might be of value
      in assessing mild variations in splenic size, because splenomegaly is the most
      common manifestation of splenic involvement in many disorders.

PMID- 9038126
TI  - MR imaging characteristics of hepatic tumors.
AB  - There is no doubt that radiologists play an increasingly important role in the
      detection of focal liver lesions, and in the evaluation of persistent or
      recurrent malignant disease after treatment. The characterization of focal liver
      lesions depends on the clinical integration of the information generated by
      different radiologic techniques. Most often, MR imaging is quite effective in
      liver tumor characterization. Our purpose is to provide an overview of the MR
      characteristics of the most commonly encountered liver tumors and their
      differential diagnosis, with the most accepted reliable proof of the lesion type
      in a clinical environment. Radiologists must know the level of confidence they
      can reach in a given diagnosis, and the influence that this diagnosis has in the
      patient's management. With this knowledge, radiologists decide whether to leave
      or follow-up the lesion, perform tissue samples, or carry out therapeutic
      procedures.

PMID- 9038127
TI  - Subcutaneous implantation metastasis of a cholangiocarcinoma of the bile duct
      after percutaneous transhepatic biliary drainage (PTBD).
AB  - Percutaneous transhepatic biliary drainage (PTBD) is the basis for most biliary
      interventional procedures. We recently observed the occurrence of a subcutaneous
      implantation metastasis after PTBD in a patient with incurable
      cholangiocarcinoma. Although tumor cell seeding along the catheter tract is a
      very rare complication, we think that PTBD should be avoided when curative
      resection is planned.

PMID- 9038128
TI  - Sonographic detection of intragastric blood clot.
AB  - An intragastric blood clot suggested by sonography and later confirmed at upper
      gastrointestinal series and at gastroscopy is reported. Sonographic findings were
      a moveable mass within stomach presenting as an arc-like hyperechoic surface with
      a strong posterior resonance artifact. Compression of the mass with a transducer
      induced the mass to move from antrum to corpus within stomach. We think that the
      demonstration of a blood clot within stomach can be suggested on the basis of
      typical sonographic findings as a secondary sign of a bleeded gastric or duodenal
      ulcer.

PMID- 9038129
TI  - 1H T1 and T2 measurements of the MR imaging contrast agents Gd-DTPA and Gd-DTPA
      BMA at 1.5T.
AB  - We report in vitro T1 and T2 relaxation studies for the open-chain complexes Gd
      DTPA and Gd-DTPA BMA. Measurements were performed on phantoms containing aqueous
      and plasma solutions of different concentrations by MR imaging in a 1.5T
      superconducting whole-body scanner. Longitudinal relaxation times T1 were
      evaluated from serial turbo-FLASH experiments for concentrations less than 1 mM,
      whereas for larger concentrations the values were obtained from a standard
      inversion recovery (IR) sequence. Transverse relaxation times T2 were determined
      using multi-echo spin-echo MRI protocols. The T1 and T2 relaxivities of the
      nonionic Gd-DTPA BMA are similar to those of the Gd-DTPA. The temperature
      dependencies of the relaxivities were determined over a temperature interval
      ranging from 21 to 50 degrees C and were found to be slightly different for the
      two contrast agents. In the case of Gd-DTPA BMA a larger deviation of the
      expected temperature behavior of the relaxivities was observed as compared with
      Gd-DTPA. Deviations from a strictly linear dependence of relaxation times on
      temperature were found at lower concentrations in aqueous solutions. In plasma
      solutions a high T1/T2 ratio was observed for low concentrations, which decreased
      monotonically with increasing concentrations.

PMID- 9038131
TI  - Correlation of lesions in the hippocampal region noted on MR images with clinical
      features.
AB  - The purpose of our work was to compare the MR imaging findings of obvious
      hippocampal and/or juxtahippocampal lesions with corresponding clinical features.
      Magnetic resonance images of 63 patients with obvious lesions in the hippocampal
      and/or juxtahippocampal regions were reviewed and their findings were correlated
      with patients' clinical characteristics. Based on the MR and clinical findings,
      the patients were divided into four groups: (a) 26 patients with space occupying
      lesions or suspected vascular malformation frequently causing symptomatic
      temporal epilepsy; (b) 14 with hippocampal infarcts, which when left-sided or
      bilateral caused amnesia; (c) 11 with encephalitis and 5 with old temporal
      contusion usually accompanied by both amnesia and epilepsy; and (d) 7 with
      temporal atrophy and progressive dementia of subacute onset. Magnetic resonance
      imaging allows precise localization and evaluation of the clinical correlates of
      hippocampal and juxtahippocampal lesions, which frequently caused symptomatic
      temporal epilepsy and/or amnesic syndrome.

PMID- 9038130
TI  - Enhancement characteristics of liver metastases, hepatocellular carcinomas, and
      hemangiomas with Gd-EOB-DTPA: preliminary results with dynamic MR imaging.
AB  - Our objective was to study Gd-EOB-DTPA for the characterization of focal liver
      lesions by means of dynamic MR imaging. A double-blind and randomized dose
      ranging phase-2 clinical trial was performed in 31 patients (liver metastases n =
      23, hepatocellular carcinoma n = 4, and hemangioma n = 4) at a field strength of
      1.0 Tesla. Gd-EOB-DTPA (Schering AG, Berlin, Germany) was administered as an IV
      bolus (12.5, 25, or 50 micromol/kg body weight) with dynamic T1-weighted MRI
      during the distribution and cellular uptake of the contrast agent at multiple
      time points up to 45 min post contrast. Dynamic changes in tumor signal
      intensity, tumor-liver contrast, enhancement patterns, side effects, and adverse
      events were evaluated. Monitoring of vital signs revealed no significant changes
      during bolus injection of Gd-EOB-DTPA. Liver metastases demonstrated an
      inhomogeneous uptake of Gd-EOB-DTPA during the distribution phase with a washout
      effect on delayed images > 3 min and highest tumor-liver contrast 20 and 45 min
      post contrast. Hepatocellular carcinomas showed prolonged enhancement as compared
      with metastases and hemangiomas. Hemangiomas exhibited an early peripheral
      nodular enhancement with subsequent partial or complete filling, persisting
      enhancement < 10 min following injection of Gd-EOB-DTPA, and delayed washout as
      compared with liver metastases. Initial clinical experience suggests that Gd-EOB
      DTPA as a bolus injectable hepatobiliary MR contrast agent may offer useful
      features for the characterization of focal liver lesions.

PMID- 9038132
TI  - CT and MRI of sellar spine with upward extension of the pituitary gland: case
      report.
AB  - This is a report of CT and MRI findings in a patient with a sellar spine which
      caused deformity of the pituitary gland. The sellar spine is an infrequent
      anatomical variant characterized by an osseous spine which arises in the midline
      from the anterior aspect of the dorsum sellae and extends into the pituitary
      fossa. The CT and MRI findings of sellar spine have been described in previous
      reports; however, only one investigator reported deformity of the pituitary gland
      as revealed by CT. This is the first report of the MRI finding of the sellar
      spine associated with a deformity and superior extension of the pituitary gland,
      mimicking pituitary hypertrophy.

PMID- 9038133
TI  - Spinal cord herniation: report of two cases and review of the literature.
AB  - Idiopathic herniation of the spinal cord is an extremely rare disorder which may
      cause progressive myelopathy. Two cases of this entity reported herein were both
      examined using MRI and CT myelography. The typical appearance of this disease
      with or without a dorsal intradural arachnoid cyst is focal ventral displacement
      of the mid-thoracic spinal cord, mimicking an isolated intradural spinal
      arachnoid cyst on MRI. CT myelography using thin slice sections is useful in the
      diagnosis of this disease.

PMID- 9038134
TI  - Regulation of the low molecular weight phosphotyrosine phosphatase by
      phosphorylation at tyrosines 131 and 132.
AB  - Activation of resting T lymphocytes is initiated by rapid but transient tyrosine
      phosphorylation of a number of cellular proteins. Several protein tyrosine
      kinases and protein tyrosine phosphatases are known to be important for this
      response. Here we report that normal T lymphocytes express the B isoform of low
      molecular weight protein tyrosine phosphatase B (LMPTP-B). The cDNA was cloned
      from Jurkat T cells, and an antiserum was raised against it. LMPTP
      immunoprecipitated from resting Jurkat T cells was found to be tyrosine
      phosphorylated. On stimulation of the cells through their T cell antigen
      receptor, the phosphotyrosine content of LMPTP-B declined rapidly. In co
      transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP, whereas Csk,
      Zap, and Jak2 did not. Most of the phosphate was located at Tyr-131, and some was
      also located at Tyr-132. Incubation of wild-type LMPTP with Lck and adenosine 5'
      O-(thiotriphosphate) caused a 2-fold increase in the activity of LMPTP. Site
      directed mutagenesis showed that Tyr-131 is important for the catalytic activity
      of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr
      132, is responsible for the activation.

PMID- 9038135
TI  - Hypoxia-inducible factor-1 mediates transcriptional activation of the heme
      oxygenase-1 gene in response to hypoxia.
AB  - Exposure of rats to hypoxia (7% O2) markedly increased the level of heme
      oxygenase-1 (HO-1) mRNA in several tissues. Accumulation of HO-1 transcripts was
      also observed after exposure of rat aortic vascular smooth muscle (VSM) cells to
      1% O2, and this induction was dependent on gene transcription. Activation of the
      mouse HO-1 gene by all agents thus far tested is mediated by two 5'-enhancer
      sequences, SX2 and AB1, but neither fragment was responsive to hypoxia in VSM
      cells. Hypoxia-dependent induction of the chloramphenicol acetyltransferase (CAT)
      reporter gene was mediated by a 163-bp fragment located approximately 9.5
      kilobases upstream of the transcription start site. This fragment contains two
      potential binding sites for hypoxia-inducible factor 1 (HIF-1). A role for HIF-1
      in HO-1 gene regulation was established by the following observations: 1) HIF-1
      specifically bound to an oligonucleotide spanning these sequences, 2) mutation of
      these sequences abolished HIF-1 binding and hypoxia-dependent gene activation in
      VSM cells, 3) hypoxia increased HIF-1alpha and HIF-1beta protein levels in VSM
      cells, and 4) hypoxia-dependent HO-1 mRNA accumulation was not observed in mutant
      hepatoma cells lacking HIF-1 DNA-binding activity. Taken together, these data
      demonstrate that hypoxia induces HO-1 expression in animal tissues and cell
      cultures and implicate HIF-1 in this response.

PMID- 9038136
TI  - Carbon isotope effects on the fructose-1,6-bisphosphate aldolase reaction, origin
      for non-statistical 13C distributions in carbohydrates.
AB  - The kinetic and equilibrium isotope effects on the fructose-1, 6-bisphosphate
      aldolase reaction have been determined using the rabbit muscle enzyme. The
      natural 13C abundance for both atoms participating in the bond splitting were
      measured in position C-1 of dihydroxyacetone phosphate and glyceraldehyde 3-P
      after irreversible conversion to glycerol-3-P and 3-phosphoglycerate,
      respectively, and chemical degradation. The carbon isotope effects were
      determined comparing the 13C content of the corresponding positions after partial
      and complete turnover, and after complete equilibration of the reactants.
      13(Vmax/Km) on C-3 was 1.016 +/- 0.007 and 0.997 +/- 0.009 on position C-4, and
      the equilibrium isotope effects K12/K13 on these positions were 1.0036 +/- 0.0002
      and 1.0049 +/- 0.0001. The observed kinetic isotope effect on C-3 is discussed to
      originate from the formation of the enamine, which comes to equilibrium before
      the rate determining release of glyceraldehyde 3-P from the ternary complex. The
      equilibrium isotope effect is seen as the reason for an earlier-found relative
      13C enrichment in position C-3 and C-4 of glucose and for varying enrichments in
      13C of carbohydrates from different compartments of cells. The kinetic isotope
      effect is suggested to cause 13C discriminations in the C-3 pool in context with
      the hexose formation in competition with other dihydroxyacetone phosphate
      turnover reactions.

PMID- 9038137
TI  - Anionic phospholipids activate ATP-sensitive potassium channels.
AB  - The ATP-sensitive potassium channel (KATP) controls insulin release in pancreatic
      beta-cells and also modulates important functions in other cell types. In this
      study we report that anionic phospholipids activated KATP in pancreatic beta
      cells, cardiac myocytes, skeletal muscle cells, and a cloned KATP composed of two
      subunits (SUR/Kir6. 2) stably expressed in a mammalian cell line. The
      effectiveness was proportional to the number of negative charges on the head
      group of the anionic phospholipid. Screening negative charges with polyvalent
      cations antagonized the effect. Enzymatic treatment with phospholipases that
      reduced charge on the lipids also reduced or eliminated the effect. These results
      suggest that intact phospholipids with negative charges are the critical
      requirement for activation of KATP, in distinction from the usual cell signaling
      pathway through phospholipids that requires cleavage. Mutations of two positively
      charged amino acid residues at the C terminus of Kir6. 2 accelerated loss of
      channel activity and reduced the activating effects of phospholipids, suggesting
      involvement of this region in the activation. Metabolism of anionic phospholipids
      in plasmalemmal membrane may be a novel and general mechanism for regulation of
      KATP and perhaps other ion channels in the family of inward rectifiers.

PMID- 9038138
TI  - Alanine-scanning mutagenesis of a putative substrate recognition site in human
      cytochrome P450 3A4. Role of residues 210 and 211 in flavonoid activation and
      substrate specificity.
AB  - Alanine-scanning mutagenesis was performed on amino acid residues 210-216 of
      cytochrome P450 3A4, the major drug-metabolizing enzyme of human liver.
      Mutagenesis of this region, which has been proposed to align with the C-terminal
      ends of F-helices from cytochromes P450BM-3, P450terp, and P450cam, served as a
      test of the applicability of the substrate recognition site model of Gotoh
      (Gotoh, O. (1992) J. Biol. Chem. 267, 83-90) to P450 3A4. The results, using two
      steroid substrates, indicated that substitution of Ala for Leu210 altered the
      responsiveness to the effector alpha-naphthoflavone and the regioselectivity of
      testosterone hydroxylation. Replacement of Leu211 by Ala also decreased the
      stimulation by alpha-naphthoflavone, whereas mutations at residues 212-216 had
      little effect. The diminished flavonoid responses of the 210 and 211 mutants were
      observed over a wide range of progesterone and alpha-naphthoflavone
      concentrations. Further characterization was performed with the additional
      effectors beta-naphthoflavone, flavone, and 4-chromanone. The finding that P450
      3A4 with one altered residue, Leu210 --> Ala, can have both an altered
      testosterone hydroxylation profile and response to flavonoid stimulation provides
      evidence that the substrate binding and effector sites are at least partially
      overlapping.

PMID- 9038139
TI  - Charged residues in transmembrane domains II and XI of a vesicular monoamine
      transporter form a charge pair that promotes high affinity substrate recognition.
AB  - Vesicular monoamine transporters package monoamine neurotransmitters into
      secretory vesicles for regulated exocytotic release. Both vesicular monoamine
      transporter 1 and 2 contain several charged residues predicted to reside within
      transmembrane domains (TMDs), and conservation of these residues in multiple
      species and in other members of the gene family suggest important roles in
      transporter structure and function. To determine the role of these residues, we
      have used site-directed mutagenesis. Replacement of Asp-263 in TMD6 with Asn
      (D263N) had no effect on transport activity. However, replacement of Lys-139 in
      TMD2 with Ala (K139A), Asp-400 in TMD10 with Asn (D400N), or Asp-427 in TMD11
      with Asn (D427N) eliminated transport activity despite normal levels of protein
      expression. Remarkably, the double mutant K139A/D427N showed substantial
      transport activity, suggesting that Lys-139 and Asp-427 interact to form an ion
      pair in the native protein and hence that TMD2 occurs next to TMD11. Nonetheless,
      the double mutant showed reduced apparent affinity for serotonin and reduced
      ability of serotonin to inhibit reserpine binding, suggesting that although not
      required for activity, the ion pair promotes high affinity interaction with the
      substrate. In addition, a double mutant in which the polarity of the charged
      residues was reversed (K139D/D427K) showed no active transport. Remarkably,
      however, this mutant displayed normal reserpine binding that remained coupled to
      DeltaH+, but serotonin failed to inhibit reserpine binding, suggesting that the
      charge reversal specifically disrupts substrate recognition.

PMID- 9038140
TI  - The serine/threonine phosphatase inhibitor calyculin A induces rapid degradation
      of IkappaBbeta. Requirement of both the N- and C-terminal sequences.
AB  - Signal-initiated activation of the transcription factor NF-kappaB is mediated
      through proteolysis of its cytoplasmic inhibitory proteins IkappaBalpha and
      IkappaBbeta. While most NF-kappaB inducers trigger the degradation of
      IkappaBalpha, only certain stimuli are able to induce the degradation of
      IkappaBbeta. The degradation of IkappaBalpha is targeted by its site-specific
      phosphorylations, although the mechanism underlying the degradation of
      IkappaBbeta remains elusive. In the present study, we have analyzed the effect of
      phosphatase inhibitors on the proteolysis of IkappaBbeta. We show that the
      serine/threonine phosphatase inhibitor calyculin A induces the
      hyperphosphorylation and subsequent degradation of IkappaBbeta in both human
      Jurkat T cells and the murine 70Z-3 preB cells, which is associated with the
      nuclear expression of active NF-kappaB. The calyculin A-mediated degradation of
      IkappaBbeta is further enhanced by the cytokine tumor necrosis factor-alpha (TNF
      alpha), although TNF-alpha alone is unable to induce the degradation of
      IkappaBbeta. Mutational analyses have revealed that the inducible degradation of
      IkappaBbeta induced by calyculin A, and TNF-alpha requires two N-terminal serines
      (serines 19 and 23) that are homologous to the inducible phosphorylation sites
      present in IkappaBalpha. Furthermore, the C-terminal 51 amino acid residues,
      which are rich in serines and aspartic acids, are also required for the inducible
      degradation of IkappaBbeta. These results suggest that the degradation signal of
      IkappaBbeta may be controlled by the opposing actions of protein kinases and
      phosphatases and that both the N- and C-terminal sequences of IkappaBbeta are
      required for the inducible degradation of this NF-kappaB inhibitor.

PMID- 9038141
TI  - The juxtamembrane, cytosolic region of the epidermal growth factor receptor is
      involved in association with alpha-subunit of Gs.
AB  - Previously, we have demonstrated that epidermal growth factor (EGF) can stimulate
      adenylyl cyclase activity via activation of Gs in the heart. Moreover, we have
      recently shown that Gsalpha is phosphorylated by the EGF receptor protein
      tyrosine kinase and that the juxtamembrane region of the EGF receptor can
      stimulate Gs directly. Therefore, employing isolated cardiac membranes, the two
      hybrid assay, and in vitro association studies with purified EGF receptor and
      Gsalpha we have investigated Gsalpha complex formation with the EGF receptor and
      elucidated the region in the receptor involved in this interaction. In isolated
      cardiac membranes, immunoprecipitation of EGF receptor was accompanied by co
      immunoprecipitation of Gsalpha. In the yeast two-hybrid assay, the cytosolic
      domain of the EGF receptor and the N-terminal 64 amino acids of this region
      (Met644-Trp707) associated with Gsalpha. However, interactions of these regions
      of the EGF receptor with constitutively active Gsalpha were diminished in the two
      hybrid assay. Employing purified proteins, our studies demonstrate that the EGF
      receptor, directly and stoichiometrically, associates with Gsalpha (1 mol of
      Gsalpha/mol of EGF receptor). This association was not altered in the presence or
      absence of ATP and therefore, was independent of tyrosine phosphorylation of
      either of the proteins. Peptides corresponding to the juxtamembrane region of the
      receptor decreased association of the EGF receptor with Gsalpha. However, neither
      the C-terminally truncated EGF receptor (Delta1022-1186) nor a peptide
      corresponding to residues 985-996 of the receptor altered association with
      Gsalpha, thus indicating the selectivity of the G protein interaction with the
      juxtamembrane region. Interestingly, peptides corresponding to N and C termini of
      Gsalpha did not alter the association of Gsalpha with the EGF receptor.
      Consistent with the findings from the two-hybrid assay where constitutively
      active Gsalpha poorly associated with the EGF receptor, in vitro experiments with
      purified proteins also demonstrated that activation of Gsalpha by guanosine 5'-3
      O-(thio)triphosphate decreased the association of G protein with the EGF
      receptor. Thus we conclude that the juxtamembrane region of the EGF receptor,
      directly and stoichiometrically, associates with Gsalpha and that upon activation
      of Gsalpha this association is decreased.

PMID- 9038143
TI  - In vitro kinetic studies of formation of antigenic advanced glycation end
      products (AGEs). Novel inhibition of post-Amadori glycation pathways.
AB  - Nonenzymatic protein glycation (Maillard reaction) leads to heterogeneous, toxic,
      and antigenic advanced glycation end products ("AGEs") and reactive precursors
      that have been implicated in the pathogenesis of diabetes, Alzheimer's disease,
      and normal aging. In vitro inhibition studies of AGE formation in the presence of
      high sugar concentrations are difficult to interpret, since AGE-forming
      intermediates may oxidatively arise from free sugar or from Schiff base
      condensation products with protein amino groups, rather than from just their
      classical Amadori rearrangement products. We recently succeeded in isolating an
      Amadori intermediate in the reaction of ribonuclease A (RNase) with ribose
      (Khalifah, R. G., Todd, P., Booth, A. A., Yang, S. X., Mott, J. D., and Hudson,
      B. G. (1996) Biochemistry 35, 4645-4654) for rapid studies of post-Amadori AGE
      formation in absence of free sugar or reversibly formed Schiff base precursors to
      Amadori products. This provides a new strategy for a better understanding of the
      mechanism of AGE inhibition by established inhibitors, such as aminoguanidine,
      and for searching for novel inhibitors specifically acting on post-Amadori
      pathways of AGE formation. Aminoguanidine shows little inhibition of post-Amadori
      AGE formation in RNase and bovine serum albumin, in contrast to its apparently
      effective inhibition of initial (although not late) stages of glycation in the
      presence of high concentrations of sugar. Of several derivatives of vitamins B1
      and B6 recently studied for possible AGE inhibition in the presence of glucose
      (Booth, A. A., Khalifah, R. G., and Hudson, B. G. (1996) Biochem. Biophys. Res.
      Commun. 220, 113-119), pyridoxamine and, to a lesser extent, thiamine
      pyrophosphate proved to be novel and effective post-Amadori inhibitors that
      decrease the final levels of AGEs formed. Our mechanism-based approach to the
      study of AGE inhibition appears promising for the design and discovery of novel
      post-Amadori AGE inhibitors of therapeutic potential that may complement others,
      such as aminoguanidine, known to either prevent initial sugar attachment or to
      scavenge highly reactive dicarbonyl intermediates.

PMID- 9038142
TI  - Arfaptin 1, a putative cytosolic target protein of ADP-ribosylation factor, is
      recruited to Golgi membranes.
AB  - ADP-ribosylation factors (ARFs) have been implicated in vesicle transport in the
      Golgi complex. Employing yeast two-hybrid screening of an HL60 cDNA library using
      a constitutively active mutant of ARF3 (ARF3.Q71L), as a probe, we have
      identified a cDNA encoding a novel protein with a calculated molecular mass of
      38.6 kDa, which we have named arfaptin 1. The mRNA of arfaptin 1 was ubiquitously
      expressed, and recombinant arfaptin 1 bound preferentially to class I ARFs,
      especially ARF1, but only in the GTP-bound form. The interactions were
      independent of myristoylation of ARF. Arfaptin 1 in cytosol was recruited to
      Golgi membranes by ARF in a guanosine 5'-O-(3-thiotriphosphate)-dependent and
      brefeldin A-sensitive manner. When expressed in COS cells, arfaptin 1 was
      localized to the Golgi complex. The yeast two-hybrid system yielded another
      clone, which encoded a putative protein, which we have named arfaptin 2. This
      consisted of the same number of amino acids as arfaptin 1 and was 60% identical
      to it. Arfaptin 2 was also ubiquitously expressed and bound to the GTP-, but not
      GDP-liganded form of class I ARFs, especially ARF1. These results suggest that
      arfaptins 1 and 2 may be direct target proteins of class 1 ARFs. Arfaptin 1 may
      be involved in Golgi function along with ARF1.

PMID- 9038144
TI  - Site-directed mutagenesis of glutamate 166 in two beta-lactamases. Kinetic and
      molecular modeling studies.
AB  - The catalytic pathway of class A beta-lactamases involves an acyl-enzyme
      intermediate where the substrate is ester-linked to the Ser-70 residue. Glu-166
      and Lys-73 have been proposed as candidates for the role of general base in the
      activation of the serine OH group. The replacement of Glu-166 by an asparagine in
      the TEM-1 and by a histidine in the Streptomyces albus G beta-lactamases yielded
      enzymes forming stable acyl-enzymes with beta-lactam antibiotics. Although
      acylation of the modified proteins by benzylpenicillin remained relatively fast,
      it was significantly impaired when compared to that observed with the wild-type
      enzyme. Moreover, the E166N substitution resulted in a spectacular modification
      of the substrate profile much larger than that described for other mutations of
      Omega-loop residues. Molecular modeling studies indicate that the displacement of
      the catalytic water molecule can be related to this observation. These results
      confirm the crucial roles of Glu-166 and of the "catalytic" water molecule in
      both the acylation and the deacylation processes.

PMID- 9038145
TI  - Side reactions catalyzed by ribulose-bisphosphate carboxylase in the presence and
      absence of small subunits.
AB  - The large subunit core of ribulose-bisphosphate carboxylase from Synechococcus
      PCC 6301 expressed in Escherichia coli in the absence of its small subunits
      retains a trace of carboxylase activity (about 1% of the kcat of the holoenzyme)
      (Andrews, T. J (1988) J. Biol. Chem. 263, 12213-12219). During steady-state
      catalysis at substrate saturation, this residual activity diverted approximately
      10% of the reaction flux to 1-deoxy-D-glycero-2,3-pentodiulose-5-phosphate as a
      result of beta elimination of inorganic phosphate from the first reaction
      intermediate, the 2,3-enediol form of ribulose bisphosphate. This indicates that
      the active site's ability to stabilize and/or retain this intermediate is
      compromised by the absence of small subunits. Epimerization and isomerization of
      the substrate resulting from misprotonation of the enediol intermediate were not
      significantly exacerbated by lack of small subunits. The residual carboxylating
      activity partitioned product between pyruvate and 3-phosphoglycerate in a ratio
      similar to that of the holoenzyme, indicating that stablization of the
      penultimate three-carbon aci-acid intermediate is not perturbed by lack of small
      subunits. The underlying instability of the five-carbon enediol intermediate was
      revealed, even with the holoenzyme, under conditions designed to lead to
      exhaustion of substrate CO2 (and O2). When carboxylation (and oxygenation)
      stalled upon exhaustion of gaseous substrate, both spinach and Synechococcus
      holoenzymes continued slowly to beta eliminate inorganic phosphate from and to
      misprotonate the enediol intermediate. With carboxylation and oxygenation
      blocked, the products of these side reactions of the enediol intermediate
      accumulated to readily detectable levels, illustrating the difficulties attendant
      upon ribulose-P2 carboxylase's use of this reactive species as a catalytic
      intermediate.

PMID- 9038146
TI  - Catalysis by a new sialidase, deaminoneuraminic acid residue-cleaving enzyme
      (KDNase Sm), initially forms a less stable alpha-anomer of 3-deoxy-D-glycero-D
      galacto-nonulosonic acid and is strongly inhibited by the transition state
      analogue, 2-deoxy-2, 3-didehydro-D-glycero-D-galacto-2-nonulopyranosonic acid,
      but not by 2-deoxy-2,3-didehydro-N-acetylneuraminic acid.
AB  - Deaminoneuraminic acid residue-cleaving enzyme (KDNase Sm) is a new sialidase
      that has been induced and purified from Sphingobacterium multivorum. Catalysis by
      this new sialidase has been studied by enzyme kinetics and 1H NMR spectroscopy.
      Vmax/Km values determined for synthetic and natural substrates of KDNase Sm
      reveal that 4-methylumbelliferyl-KDN (KDNalpha2MeUmb, Vmax/Km = 0.033 min-1) is
      the best substrate for this sialidase, presumably because of its good leaving
      group properties. The transition state analogue, 2, 3-didehydro-2,3-dideoxy-D
      galacto-D-glycero-nonulosonic acid, is a strong competitive inhibitor of KDNase
      Sm (Ki = 7.7 microM versus Km = 42 microM for KDNalpha2MeUmb). 2-Deoxy-2, 3
      didehydro-N-acetylneuraminic acid and 2-deoxy-2, 3-didehydro-N-glycolylneuraminic
      acid are known to be strong competitive inhibitors for bacterial sialidases such
      as Arthrobacter ureafaciens sialidase; however, KDNase Sm activity is not
      significantly inhibited by these compounds. This observation suggests that the
      hydroxyl group at C-5 is important for recognition of the inhibitor by the
      enzyme. Reversible addition of water molecule (or hydroxide ion) to the reactive
      sialosyl cation, presumably formed at the catalytic site of KDNase Sm, eventually
      gives rise to two different adducts, the alpha- and beta-anomers of free 3-deoxy
      D-glycero-D-galacto-nonulosonic acid. 1H NMR spectroscopic studies clearly
      demonstrate that the thermodynamically less stable alpha-form is preferentially
      formed as the first product of the cleavage reaction and that isomerization
      rapidly follows, leading to an equilibrium mixture of the two isomers, the beta
      isomer being the major species at equilibrium. Therefore, we propose that KDNase
      Sm catalysis proceeds via a mechanism common to the known exosialidases, but the
      recognition of the substituent at C-5 by the enzyme differs.

PMID- 9038147
TI  - Catalytic properties and sensitivity to tentoxin of Chlamydomonas reinhardtii ATP
      synthases changed in codon 83 of atpB by site-directed mutagenesis.
AB  - The participation of the amino acid beta83 in determining the sensitivity of
      chloroplast ATP synthases to tentoxin was reported previously. We have changed
      codon 83 of the Chlamydomonas reinhardtii atpB gene by site-directed mutagenesis
      to further examine the role of this amino acid in the response of the ATP
      synthase to tentoxin and in the mechanism of ATP synthesis and hydrolysis. Amino
      acid beta83 was changed from Glu to Asp (betaE83D) and to Lys (betaE83K), and the
      highly conserved tetrapeptide betaT82-E83-G84-L85 (DeltaTEGL) was deleted. Mutant
      strains were produced by particle gun transformation of atpB deletion mutants
      cw15DeltaatpB and FUD50 with the mutated atpB genes. The transformants containing
      the betaE83D and betaE83K mutant genes grew well photoautotrophically. The
      DeltaTEGL transformant did not grow photoautotrophically, and no CF1 subunits
      were detected by immunostaining of Western blots using CF1 specific antibodies.
      The rates of ATP synthesis at clamped DeltapH with thylakoids isolated from cw15
      and the two mutants, betaE83D and betaE83K, were similar. However, only the
      phosphorylation activity of the mutant betaE83D was inhibited by tentoxin with
      50% inhibition attained at 4 microM. These results confirm that amino acid beta83
      is critical in determining the response of ATP synthase to tentoxin. The rates of
      the latent Mg-ATPase activity of the CF1s isolated from cw15, betaE83D, and
      betaE83K were similar and could be enhanced by heat, alcohols, and
      octylglucoside. As in the case of the membrane-bound enzyme, only CF1 from the
      betaE83D mutant was sensitive to tentoxin. A lower alcohol concentration was
      required for optimal stimulation of the ATPase of the betaE83K-CF1 than that of
      CF1 from the other two strains. Moreover, the optimal activity of the betaE83K
      CF1 was also lower. These results suggest that introduction of an amino acid with
      a positively charged side chain in position 83 in the "crown" domain affects the
      active conformation of the CF1-ATPase.

PMID- 9038148
TI  - Cloning and localization of a glutathione S-transferase class I gene from
      Anopheles gambiae.
AB  - 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) resistance in both adults and
      larvae of Anopheles gambiae is mediated by stage-specific glutathione S
      transferases (GSTs). On the basis of their biochemical characteristics the larval
      resistance-associated GSTs are likely to be insect class I GSTs. Aggst1-2, a
      class I GST gene, which is expressed in larvae, has been cloned from the malaria
      vector A. gambiae. The gene was inserted into a bacterial expression system, and
      the detection of 1-chloro-2,4-dinitrobenzene (CDNB) conjugating activity in
      Eschericia coli expressing the recombinant enzyme confirmed that aggst1-2 encodes
      a catalytically active GST. The gene encodes a 209 amino acid protein with 46%
      sequence similarity to a Drosophila melanogaster class I GST (GST-D1), 44%
      similarity with a Musca domestica class I GST (MdGST-1), but only low levels of
      homology with class II insect GSTs, including the adult specific AgGST2-1 from A.
      gambiae. Southern analysis of genomic DNA indicated that A. gambiae has multiple
      class I GSTs. In situ hybridization of class I genomic and cDNA clones to
      polytene chromosomes identified a single region of complementarity on chromosome
      2R division 18B, suggesting that these class I GSTs in A. gambiae are arranged
      sequentially in the genome. Three positive overlapping recombinant clones were
      identified from an A. gambiae genomic library. Mapping and partial sequencing of
      these clones suggests that there are several GSTs and truncated GST pseudogenes
      within the 30kb of DNA that these clones span.

PMID- 9038149
TI  - The inactivation and catalytic pathways of horseradish peroxidase with m
      chloroperoxybenzoic acid. A spectrophotometric and transient kinetic study.
AB  - The kinetics of the catalytic cycle and irreversible inactivation of horseradish
      peroxidase C (HRP-C) reacting with m-chloroperoxybenzoic acid (mCPBA) have been
      studied by conventional and stopped-flow spectrophotometry. mCPBA oxidized HRP-C
      to compound I with a second order-rate constant k1 = 3.6 x 10(7) M-1 s-1 at pH
      7.0, 25 degrees C. Excess mCPBA subsequently acted as a one-electron reducing
      substrate, converting compound I to compound II and compound II to resting,
      ferric enzyme. In both of these reactions, spectrally distinct, transient forms
      of the enzyme were observed (lambdamax = 411 nm, epsilon = 45 mM-1 cm-1 for
      compound I with mCPBA, and lambdamax = 408 nm, epsilon = 77 mM-1 cm-1 for
      compound II with mCPBA). The compound I-mCPBA intermediate (shown by near
      infrared spectroscopy to be identical to P965) decayed either to compound II in a
      catalytic cycle (k3 = 6.4 x 10(-3) s-1) or, in a competing inactivation reaction,
      to verdohemoprotein (ki = 3.3 x 10(-3) s-1). Thus, a partition ratio of r = 2 is
      obtained for the inactivation of ferric HRP-C by mCPBA. The intermediate formed
      from compound II with mCPBA is not part of the inactivation pathway and only
      decays via the catalytic cycle to give resting, ferric enzyme (k5 = 1.0 x 10(-3)
      s-1). The data are compared with those from earlier steady-state kinetic studies
      and demonstrate the importance of single turnover experiments. The results are
      discussed in terms of the physiologically relevant reactions of plant peroxidases
      with hydrogen peroxide.

PMID- 9038150
TI  - A novel, rapid, and highly sensitive mass assay for phosphatidylinositol 3,4,5
      trisphosphate (PtdIns(3,4,5)P3) and its application to measure insulin-stimulated
      PtdIns(3,4,5)P3 production in rat skeletal muscle in vivo.
AB  - The pivotal role of phosphatidylinositol 3-kinase (PI 3-kinase) in signal
      transduction has been well established in recent years. Receptor-regulated forms
      of PI 3-kinase are thought to phosphorylate phosphatidylinositol 4,5-bisphosphate
      (PtdIns(4,5)P2) at the 3-position of the inositol ring to give the putative lipid
      second messenger, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4, 5)P3).
      Cellular levels of PtdIns(3,4,5)P3 are currently measured by time-consuming
      procedures involving radiolabeling with high levels of 32PO4, extraction, and
      multiple chromatography steps. To avoid these lengthy and hazardous procedures,
      many laboratories prefer to assay PI 3-kinase activity in cell extracts and/or
      appropriate immunoprecipitates. Such approaches are not readily applied to
      measurements of PtdIns(3,4,5)P3 in extracts of animal tissues. Moreover, they can
      be misleading since the association of PI 3-kinases in molecular complexes is not
      necessarily correlated with the enzyme's activity state. Direct measurements of
      PtdIns(3,4,5)P3 would also be desirable since its concentration may be subject to
      additional control mechanisms such as activation or inhibition of the
      phosphatases responsible for PtdIns(3,4,5)P3 metabolism. We now report a simple,
      reproducible isotope dilution assay which detects PtdIns(3,4,5)P3 at subpicomole
      sensitivity, suitable for measurements of both basal and stimulated levels of
      PtdIns(3,4,5)P3 obtained from samples containing approximately 1 mg of cellular
      protein. Total lipid extracts, containing PtdIns(3,4,5)P3, are first subjected to
      alkaline hydrolysis which results in the release of the polar head group
      Ins(1,3,4,5)P4. The latter is measured by its ability to displace
      [32P]Ins(1,3,4,5)P4 from a highly specific binding protein present in cerebellar
      membrane preparations. We show that this assay solely detects PtdIns(3,4,5)P3 and
      does not suffer from interference by other compounds generated after alkaline
      hydrolysis of total cellular lipids. Measurements on a wide range of cells,
      including rat-1 fibroblasts, 1321N1 astrocytoma cells, HEK 293 cells, and rat
      adipocytes, show wortmannin-sensitive increased levels of PtdIns(3,4,5)P3 upon
      stimulation with appropriate agonists. The enhanced utility of this procedure is
      further demonstrated by measurements of PtdIns(3,4,5)P3 levels in tissue derived
      from whole animals. Specifically, we show that stimulation with insulin increases
      PtdIns(3,4,5)P3 levels in rat skeletal muscle in vivo with a time course which
      parallels the activation of protein kinase B in the same samples.

PMID- 9038151
TI  - The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA.
AB  - A cDNA was isolated from a human monocyte library that encodes the P2X7 receptor;
      the predicted protein is 80% identical to the rat receptor. Whole cell recordings
      were made from human embryonic kidney cells transfected with the human cDNA and
      from human macrophages. Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)
      benzoyl-ATP elicited cation-selective currents. When compared with the rat P2X7
      receptor, these effects required higher concentrations of agonists, were more
      potentiated by removal of extracellular magnesium ions, and reversed more rapidly
      on agonist removal. Longer applications of agonists permeabilized the cells, as
      evidenced by uptake of the propidium dye YO-PRO1, but this was less marked than
      for cells expressing the rat P2X7 receptor. Expression of chimeric molecules
      indicated that some of the differences between the rat and human receptor could
      be reversed by exchanging the intracellular C-terminal domain of the proteins.

PMID- 9038152
TI  - Tumor necrosis factor alpha enhances the expression of the interleukin (IL)-4
      receptor alpha-chain on endothelial cells increasing IL-4 or IL-13-induced Stat6
      activation.
AB  - Functional receptors for interleukin (IL)-4 and IL-13 on endothelial cells
      consist of the 130-kDa IL-4 receptor alpha-chain (IL-4Ralpha) and a 65-75-kDa IL
      13 binding subunit that are expressed in a ratio of about 1:3, respectively. The
      restricted number of IL-4Ralpha limits subunit heterodimerization and in turn
      receptor-mediated signaling. We report here, the effects of tumor necrosis factor
      alpha (TNF-alpha) on the expression of the receptor subunits for IL-4 and IL-13.
      By flow cytofluorometry and receptor-binding analysis of iodinated IL-4 and IL
      13, stimulation with TNF-alpha-induced a 2-3-fold increase of the IL-4Ralpha
      expression. The up-regulation was also confirmed at the transcriptional level by
      reverse transcription-polymerase chain reaction. Radioligand cross-linking
      experiments revealed no change in the subunit composition of the TNF-alpha
      induced receptor complex. Nevertheless, TNF-alpha stimulation led to increased
      activation of the IL-4-specific signal transducers and activators of
      transcription protein (Stat6) by IL-4 and IL-13. Thus, TNF-alpha corrects the
      subunit imbalance of the endothelial IL-4.IL-13 receptor complex thereby
      increasing receptor heterodimerization and in turn the signaling capability by IL
      4 and IL-13.

PMID- 9038153
TI  - Selective activation of cAMP-dependent protein kinase type I inhibits rat natural
      killer cell cytotoxicity.
AB  - The present study examines the expression and involvement of cAMP-dependent
      protein kinase (PKA) isozymes in cAMP-induced inhibition of natural killer (NK)
      cell-mediated cytotoxicity. Rat interleukin-2-activated NK cells express the PKA
      alpha-isoforms RIalpha, RIIalpha, and Calpha and contain both PKA type I and type
      II. Prostaglandin E2, forskolin, and cAMP analogs all inhibit NK cell lysis of
      major histocompatibility complex class I mismatched allogeneic lymphocytes as
      well as of standard tumor target cells. Specific involvement of PKA in the cAMP
      induced inhibition of NK cell cytotoxicity is demonstrated by the ability of a
      cAMP antagonist, (Rp)-8-Br-adenosine 3',5'-cyclic monophosphorothioate, to
      reverse the inhibitory effect of complementary cAMP agonist (Sp)-8-Br-adenosine
      3',5'-cyclic monophosphorothioate. Furthermore, the use of cAMP analog pairs
      selective for either PKA isozyme (PKA type I or PKA type II), shows a
      preferential involvement of the PKA type I isozyme, indicating that PKA type I is
      necessary and sufficient to completely abolish killer activatory signaling
      leading to NK cell cytotoxicity. Finally, combined treatment with phorbol ester
      and ionomycin maintains NK cell cytotoxicity and eliminates the cAMP-mediated
      inhibition, demonstrating that protein kinase C and Ca2+-dependent events
      stimulate the cytolytic activity of NK cells at a site distal to the site of
      cAMP/PKA action.

PMID- 9038154
TI  - Complexes of focal adhesion kinase (FAK) and Crk-associated substrate (p130(Cas))
      are elevated in cytoskeleton-associated fractions following adhesion and Src
      transformation. Requirements for Src kinase activity and FAK proline-rich motifs.
AB  - The focal adhesion kinase (FAK) and Crk-associated substrate, p130(Cas) (Cas),
      have been implicated in diverse signaling pathways including those mediated by
      integrins, G-protein-coupled receptors, tyrosine kinase receptors, and the v-src
      and v-crk oncogenes. The recent identification of a direct interaction between
      FAK and Cas prompted the examination of potential regulation of FAK.Cas complexes
      by factors that result in concomitant increase in their phosphotyrosine content,
      namely cell adhesion and transformation by Src. Both conditions resulted in
      elevated FAK.Cas complex levels in nonionic detergent-insoluble fractions,
      indicating increased association with the cytoskeleton. For activated Src, this
      effect requires an active Src catalytic domain but not its Src homology 2 (SH2)
      or Src homology 3 (SH3) domains. FAK kinase domain tyrosines 576 and 577 are also
      required, suggesting that direct phosphorylation of these sites by Src may
      influence the solubility and/or stability of the complex. FAK-Cas association was
      only observed in the context of Cas binding to at least one of two distinct
      proline-rich sites on FAK. These findings firmly establish a direct interaction
      between FAK and Cas and demonstrate that Src can influence the subcellular
      localization of the complex by a tyrosine phosphorylation-dependent mechanism.

PMID- 9038155
TI  - Functional consequences of truncating amino acid side chains located at a
      calmodulin-peptide interface.
AB  - To test the relevance of the calmodulin-peptide crystal structures to their
      respective calmodulin-enzyme interactions, amino acid side chains in calmodulin
      were altered at positions that interact with the calmodulin-binding peptide of
      smooth muscle myosin light chain kinase but not with the calmodulin kinase
      IIalpha peptide. Since shortening the side chains of Trp-800, Arg-812, and Leu
      813 in smooth muscle myosin light chain kinase abrogated calmodulin-dependent
      activation (Bagchi, I. C., Huang, Q., and Means, A. R. (1992) J. Biol. Chem. 267,
      3024-3029), substitutions were introduced at positions in calmodulin which
      contact residues corresponding to Arg-812 and Leu-813 in the smooth muscle myosin
      light chain kinase peptide. Assays of smooth muscle myosin light chain kinase
      with the calmodulin mutants M51A,V55A, L32A,M51A,V55A, and L32A,M51A,V55A,F68L,
      M71A exhibited 60%, 25%, and less than 1% of maximal activity respectively,
      whereas the mutants fully activated calmodulin kinase IIalpha. Alanine
      substitutions at positions on the smooth muscle myosin light chain kinase
      peptide, corresponding to Trp-800 and Arg-812 in the enzyme, produced an 8-fold
      increase in the enzyme inhibition constant in contrast with the abolition of
      calmodulin binding by similar mutations in the parent enzyme.

PMID- 9038156
TI  - Isolation, analysis, and deletion of the gene coding for subunit IV of cytochrome
      c oxidase in Paracoccus denitrificans.
AB  - The gene coding for subunit IV of the cytochrome c oxidase in Paracoccus
      denitrificans has been cloned and sequenced. The derived amino acid sequence
      shows no significant homology to any known protein. Gene deletion has no
      consequences for the integrity of the complex and its spectral and enzymatic
      properties. Complementation of the deletion mutant in trans results in expression
      of subunit IV; sequence analysis of the 5'-noncoding region leads to the
      identification of a putative promoter sequence.

PMID- 9038157
TI  - Characterization of heparin and heparan sulfate domains binding to the long
      splice variant of platelet-derived growth factor A chain.
AB  - Platelet-derived growth factors (PDGFs) are homo- or heterodimers of two related
      polypeptides, known as A and B chains. The A chain exists as two splice variants
      due to the alternative usage of exons 6 (PDGF-AL, longer) and 7 (PDGF-AS,
      shorter). Exon 6 encodes an 18-amino acid sequence rich in basic amino acid
      residues, which has been implicated as a cell retention signal. Several lines of
      evidence indicate that the retention is due to binding of PDGF-AL to
      glycosaminoglycans, especially to heparan sulfate. We have analyzed the
      saccharide domains of smooth muscle cell-derived heparan sulfate involved in this
      interaction. Furthermore, we have employed selectively modified heparin
      oligosaccharides to elucidate the dependence of the binding on different sulfate
      groups and on fragment length. The shortest PDGF-AL binding domain consists of 6
      8 monosaccharide units. Studies using selectively desulfated heparins and heparin
      fragments suggest that N-, 2-O-, and 6-O-sulfate groups all contribute to the
      interaction. Structural comparison of heparan sulfate oligosaccharides separated
      by affinity chromatography on immobilized PDGF-AL showed that the bound pool was
      enriched in -IdceA(2-OSO3)-GlcNSO3(6-OSO3)- disaccharide units. Furthermore,
      analogous separation of a partially O-desulfated heparin decamer preparation,
      using a highly selective nitrocellulose filter-trapping system, yielded a PDGF-AL
      bound fraction in which more than half of the disaccharide units had the
      structure -IdceA(2-OSO3)-GlcNSO3(6-OSO3)-. Our results suggest that the
      interaction between PDGF-AL and heparin/heparan sulfate is mediated via N
      sulfated saccharide domains containing both 2-O- and 6-O-sulfate groups.

PMID- 9038158
TI  - Site-directed mutation of Nm23-H1. Mutations lacking motility suppressive
      capacity upon transfection are deficient in histidine-dependent protein
      phosphotransferase pathways in vitro.
AB  - We previously compared the structure and motility suppressive capacity of nm23-H1
      by transfection of wild type and site-directed mutant forms into breast carcinoma
      cells. Wild type nm23-H1 and an nm23-H1(S44A) (serine 44 to alanine) mutant
      suppressed motility, whereas the nm23-H1(P96S), nm23-H1(S120G), and to a lesser
      extent, nm23-H1(S120A) mutant forms failed to do so. In the present study wild
      type and mutant recombinant Nm23-H1 proteins have been produced, purified, and
      assayed for phosphorylation and phosphotransfer activities. We report the first
      association of Nm23-H1 mutations lacking motility suppressive capacity with
      decreased in vitro activity in histidine-dependent protein phosphotransferase
      assays. Nm23-H1(P96S), a Drosophila developmental mutation homolog, exhibited
      normal autophosphorylation and nucleoside-diphosphate kinase (NDPK)
      characteristics but deficient phosphotransfer activity in three histidine protein
      kinase assays, using succinic thiokinase, Nm23-H2, and GST-Nm23-H1 as substrates.
      Nm23-H1(S120G), found in advanced human neuroblastomas, exhibited deficient
      activity in several histidine-dependent protein phosphotransfer reactions,
      including histidine autophosphorylation, downstream phosphorylation on serines,
      and slightly decreased histidine protein kinase activity; significant NDPK
      activity was observed. The Nm23-H1(S120A) mutant was deficient in only histidine
      dependent serine autophosphorylation. Nm23-H1 and Nm23-H1(S44A) exhibited normal
      activity in all assays conducted. Based on this correlation, we hypothesize that
      a histidine-dependent protein phosphotransfer activity of Nm23-H1 may be
      responsible for its biological suppressive effects.

PMID- 9038159
TI  - Quantitative analysis of bacterial toxin affinity and specificity for glycolipid
      receptors by surface plasmon resonance.
AB  - The primary virulence factors of many pathogenic bacteria are secreted protein
      toxins which bind to glycolipid receptors on host cell surfaces. The binding
      specificities of three such toxins for different glycolipids, mainly from the
      ganglioside series, were determined by surface plasmon resonance (SPR) using a
      liposome capture method. Unlike microtiter plate and thin layer chromatography
      overlay assays, the SPR/liposome methodology allows for real time analysis of
      toxin binding under conditions that mimic the natural cell surface venue of these
      interactions and without any requirement for labeling of toxin or receptor.
      Compared to conventional assays, the liposome technique showed more restricted
      oligosaccharide specificities for toxin binding. Cholera toxin demonstrated an
      absolute requirement for terminal galactose and internal sialic acid residues (as
      in GM1) with tolerance for substitution with a second internal sialic acid (as in
      GD1b). Escherichia coli heat-labile enterotoxin bound to GM1 and tolerated
      removal or extension of the internal sialic acid residue (as in asialo-GM1 and
      GD1b, respectively) but not substitution of the terminal galactose of GM1.
      Tetanus toxin showed a requirement for two internal sialic acid residues as in
      GD1b. Extension of terminal galactose with a single sialic acid was tolerated to
      some extent. The SPR analyses also yielded rate and affinity constants which are
      not attainable by conventional assays. Complex binding profiles were observed in
      that the association and dissociation rate constants varied with toxin:receptor
      ratios. The sub-nanomolar affinities of cholera toxin and heat-labile enterotoxin
      for liposome-anchored gangliosides were attributable largely to very slow
      dissociation rate constants. The SPR/liposome technology should have general
      applicability in the study of glycolipid-protein interactions and in the
      evaluation of reagents designed to interfere with these interactions.

PMID- 9038160
TI  - Topological analysis of the functional mimicry between a peptide and a
      carbohydrate moiety.
AB  - The shared surface topology of two chemically dissimilar but functionally
      equivalent molecular structures has been analyzed. A carbohydrate moiety (alpha-D
      mannopyranoside) and a peptide molecule (DVFYPYPYASGS) bind to concanavalin A at
      a common binding site. The cross-reactivity of the polyclonal antibodies (pAbs)
      was used for understanding the topological relationship between these two
      independent ligands. The anti-alpha-D-mannopyranoside pAbs recognized various
      peptide ligands of concanavalin A, and the anti-DVFYPYPYASGS pAbs recognized the
      carbohydrate ligands, providing direct evidence of molecular mimicry. On the
      basis of differential binding of various rationally designed peptide analogs to
      the anti-alpha-D-mannopyranoside pAbs, it was possible to identify different
      peptide residues critical for the mimicry. The comparison of circular dichroism
      profiles of the designed analogs suggests that the carbohydrate mimicking
      conformation of the peptide ligand incorporates a polyproline type II structural
      fold. The concanavalin A binding activity of these analogs was found to have a
      direct correlation with the topological relationship between peptide and
      carbohydrate ligands.

PMID- 9038161
TI  - Metabolic and regulatory changes associated with growth of Saccharomyces
      cerevisiae in 1.4 M NaCl. Evidence for osmotic induction of glycerol
      dissimilation via the dihydroxyacetone pathway.
AB  - The salt-instigated protein expression of Saccharomyces cerevisiae during growth
      in either 0.7 or 1.4 M NaCl was studied by two-dimensional polyacrylamide gel
      electrophoresis. The 73 protein spots that were identified as more than 3-fold
      responsive in 1.4 M NaCl were further grouped by response class (halometric, low
      salt, and high-salt regulation). Roughly 40% of these responsive proteins were
      found to decrease in expression, while at higher magnitudes of change (>8-fold)
      only induction was recorded. Enolase 1 (Eno1p) was the most increasing protein by
      absolute numbers per cell, but not by -fold change, and the enzymes involved in
      glycerol synthesis, Gpd1p and Gpp2p, were also induced to a similar degree as
      Eno1p. We furthermore present evidence for salt induction of glycerol
      dissimilation via dihydroxyacetone and also identify genes putatively encoding
      the two enzymes involved; dihydroxyacetone kinase (DAK1 and DAK2) and glycerol
      dehydrogenase (YPR1 and GCY1). The GPD1, GPP2, GCY1, DAK1, and ENO1 genes all
      displayed a halometric increase in the amount of transcript. This increase was
      closely linked to the salt-induced rate of protein synthesis of the corresponding
      proteins, indicating mainly transcriptional regulation of expression for these
      genes. A consensus element with homology to the URS sequence of the ENO1 promoter
      was found in the promoters of the GPD1, GPP2, GCY1, and DAK1 genes.

PMID- 9038162
TI  - Dual control of glut1 glucose transporter gene expression by hypoxia and by
      inhibition of oxidative phosphorylation.
AB  - glut1 gene expression and glucose transport are stimulated in a variety of cells
      and tissues in response to hypoxia. glut1 is also up-regulated by inhibitors of
      oxidative phosphorylation (such as azide) in the presence of oxygen. Here, we
      test the hypothesis that hypoxia stimulates glut1 gene expression independent of
      its inhibitory effect on oxidative phosphorylation. We examined the effect of
      cobalt chloride, a known stimulator of genes responsive to reduced oxygen
      concentration per se, on GLUT1 expression under normoxic conditions and compared
      the results with the response to azide. Exposure of a rat liver cell line (Clone
      9) to 250 microM cobalt chloride increases GLUT1 mRNA content, which becomes
      evident at 2 h, reaches a maximal value of approximately 12-fold at 8 h, and
      remains elevated at approximately 8-fold at 24 h. GLUT1 mRNA was the only GLUT
      isoform expressed in control cells and in cells exposed to cobalt chloride or
      azide. The induction of GLUT1 mRNA by cobalt chloride is associated with a
      approximately 10-fold stimulation of cytochalasin B-inhibitable 3-O-methyl-D
      glucose transport at 24 h. In contrast to the rapid decrease in cell ATP levels
      and the stimulation of glucose transport in response to azide, cell ATP content
      and glucose transport remained unaltered during the initial 1-h period of
      exposure to cobalt chloride. The effect of cobalt chloride on GLUT1 mRNA content
      is mimicked by Ni(II) or Mn(II) but not by Fe(II). Employing actinomycin D, we
      found no increase in the approximately 1.5-h half-life of GLUT1 mRNA in cobalt
      chloride-treated cells, suggesting that the effect of cobalt chloride on GLUT1
      mRNA content is largely mediated at the transcriptional level; in contrast, GLUT1
      mRNA half-life increased to >8 h in azide-treated cells. In transient
      transfections we found that approximately 6 kilobase pairs (kbp) of 5'-flanking
      region of the rat glut1 promoter confers both cobalt chloride- and azide
      inducibility to a reporter gene. Deletion of approximately 2, 500 base pairs (bp)
      from the 5' end of the approximately 6-kbp DNA fragment results in a reduction of
      the response to cobalt chloride and a complete loss of the response to azide. A
      666-bp DNA segment located approximately 6.0 kbp upstream of the transcription
      start site was found to be necessary for the increase in reporter gene expression
      in response to azide, whereas a 480-bp segment located at approximately -3.5 kbp
      mediated the response to cobalt chloride. The 480-bp segment is highly homologous
      to the previously reported mouse glut1 enhancer and contains several potential
      regulatory elements, including a hypoxia-inducible element; an additional hypoxia
      inducible element is present in the 666-bp segment. Our results suggest that
      glut1 gene expression is regulated in a dual fashion by hypoxia per se and in
      response to inhibition of oxidative phosphorylation.

PMID- 9038163
TI  - Identification of the naturally occurring flavin of nitroalkane oxidase from
      fusarium oxysporum as a 5-nitrobutyl-FAD and conversion of the enzyme to the
      active FAD-containing form.
AB  - Nitroalkane oxidase from Fusarium oxysporum catalyzes the oxidation of
      nitroalkanes to aldehydes with production of nitrite and hydrogen peroxide. The
      UV-visible absorbance spectrum of the purified enzyme shows a single absorption
      peak at 336 nm with an extinction coefficient of 7.4 mM-1 cm-1. Upon denaturation
      of the enzyme at pH 7.0, a stoichiometric amount of FAD is released. The spectral
      properties of the enzyme as isolated are consistent with an N(5) adduct of the
      flavin. This is not due to a covalent linkage with the protein, since the free
      flavin adduct can be isolated from the enzyme at pH 2.1. The free flavin adduct
      shows an absorbance spectrum with a lambdamax at 346 nm (10.7 mM-1 cm-1) and is
      not fluorescent. Under alkaline conditions the free adduct decays, yielding FAD;
      the rate of this process is pH-dependent with a pKa of 7.4. Adduct decay is also
      observed with the native enzyme; in this case, however, the rate of decay is 160
      fold slower (at pH 8.0) and not dependent on pH. During this process a large
      increase in enzymatic activity ( approximately 26-fold at pH 7.0) is observed,
      the rate of which is equal to the rate of flavin adduct conversion to FAD. Thus,
      the native flavin adduct is not active but can be converted to FAD, the active
      form of the flavin. Maximal activation is pH- and FAD-dependent; two groups with
      pKa values of 5.65 +/- 0. 25 and 8.75 +/- 0.05 must be unprotonated and
      protonated, respectively. The m/z- of the free flavin adduct is 103.0645 higher
      than that of FAD, as determined by matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry. This corresponds to a molecule of nitrobutane
      linked to FAD. A mechanism is proposed for the formation in vivo of the
      nitrobutyl-FAD of nitroalkane oxidase.

PMID- 9038164
TI  - Identification of native complexes containing the yeast coactivator/repressor
      proteins NGG1/ADA3 and ADA2.
AB  - NGG1p/ADA3p and ADA2p are dual function regulators that stimulate or inhibit a
      set of yeast transcriptional activator proteins. In vitro, NGG1p and ADA2p
      associate in a complex that also contains GCN5p (Horiuchi, J., Silverman, N.,
      Marcus, G. A., and Guarente, L. (1995) Mol. Cell. Biol. 15, 1203-1209). We have
      found that NGG1p and ADA2p are coimmunoprecipitated from yeast whole cell
      extracts. In fact, <2% of cellular ADA2p was not associated with NGG1p. Also in
      agreement with their association in vivo, the stability of ADA2p and NGG1p
      depended on the presence of each other. In addition, three NGG1p- and ADA2p
      containing peak fractions were resolved by Q-Sepharose Fast Flow ion-exchange
      chromatography of whole cell extract. The presence of another high molecular mass
      complex was supported by the separation of one of the NGG1p- and ADA2p-containing
      peak fractions by gel-filtration chromatography. Together, the combination of ion
      exchange and gel-filtration chromatography suggests a total of four complexes,
      two with sizes of >2 MDa and single complexes of approximately 900 and 200 kDa.
      At least one of these complexes was found to associate with the TATA-binding
      protein (TBP) since TBP was present in immunoprecipitates with NGG1p. The
      association of TBP with the ADA proteins required amino acids 274-307 of NGG1p, a
      region of NGG1p required for activity. This supports a role for NGG1p in the
      interaction with TBP and suggests that the interaction with TBP is functionally
      relevant.

PMID- 9038166
TI  - Additional organizational features of the murine folylpolyglutamate synthetase
      gene. Two remotely situated exons encoding an alternate 5' end and proximal open
      reading frame under the control of a second promoter.
AB  - Nucleotide sequence analysis of independently isolated clones from a mouse liver
      cDNA library identified two additional splice variants of folylpolyglutamate
      synthetase (FPGS) mRNA with novel sequence at the 5' end. These variants
      incorporate two new alternatives (exons A1a and A1b) of exon 1 in the murine FPGS
      gene which are also spliced to exon 2. Exon A1a encodes most of the 5'
      untranslated region. Exon A1b encodes a downstream segment of the 5'-untranslated
      region, two ATG start codons, and a unique mitochondrial leader peptide as well
      as 15 additional amino acids of cytosolic FPGS not encoded by all previously
      identified (Roy, K., Mitsugi, K., and Sirotnak, F. M. (1996) J. Biol. Chem., 271,
      23820-23827) splice variants. It was also found by direct sequencing of genomic
      fragments that although exon A1b is spliced to exon 2, these new alternatives
      (i.e. exons A1a and A1b) to exon 1 are found approximately 9.5 kilobases upstream
      from exons B1a, B1b, and B1c. Exons A1a and A1b are separated from each other by
      a 124-nucleotide intron. Sequencing of the region 5' to exon A1a revealed a
      nucleotide sequence that was promoter-like and different from the downstream
      promoter region in the content of putative cis-acting elements. Primer extension
      analysis identified a number of potential transcription start sites within the
      more 3' end of this region. FPGS RNA transcripts incorporating exons A1a and A1b
      were detected in both normal mouse tissues, particularly, liver and kidney, and
      also to a varying extent in tumors; FPGS RNA transcripts incorporating exons B1a,
      B1b, and B1c were detected mainly in tumors. Thus, transcription of the FPGS gene
      in this tissue-specific manner appears to reflect the different usage of
      alternates to exon 1 under the control of different promoters. An unusual splice
      variant identified infrequently in a mouse liver cDNA library was 2.67 kilobases
      in size and incorporated exons A1a and A1b and a segment of the downstream
      promoter region along with exons B1c and B1b and exons 2-15.

PMID- 9038165
TI  - The promoters for human and monkey poliovirus receptors. Requirements for basic
      and cell type-specific activity.
AB  - The cellular receptors for poliovirus (PVR) are glycoproteins belonging to the
      immunoglobulin superfamily. Functional receptors for poliovirus are only
      expressed by primates; known rodent homologues lack the ability to bind virus due
      to amino acid differences. Human poliovirus infections are targeted to the
      gastrointestinal tract and, rarely, to motor neurons in the central nervous
      system. Available evidence suggests that poliovirus uses only one cellular
      receptor, implying that the tissue tropism of poliovirus is likely to be related
      to the expression of the human PVR (hPVR). However, low levels of expression of
      hPVR-specific mRNAs can be detected in many human tissues other than the apparent
      target cells. The nonpathogenic function of hPVR is unknown. For a study of the
      transcriptional control of hPVR expression, we have isolated and characterized
      the promoter of the hPVR gene. Deletion analysis defined an approximately 280
      base pair minimal promoter fragment that: 1) lacks TATA- and CAAT-like elements,
      2) is distinguished by a high GC content, and 3) promotes transcription at
      multiple start sites. The pattern of activity caused by transfection of serial 5'
      and 3'-promoter deletions is almost identical in HEp2, HeLa, COS-1, and mouse
      L929 cells, indicating a similar transcriptional regulation of the hPVR promoter
      in these cell lines. However, on transfection of Raji cells, a Burkitt's lymphoma
      cell line harboring a transcriptionally inactive hPVR gene, all promoter reporter
      constructs tested exerted only residual activity. These results suggest that the
      cis-element(s) governing cell type-specific hPVR expression resides in the
      minimal promoter region. We also report the sequences of the promoters of two
      monkey homologues to hPVR (AGMalpha1 and AGMalpha2). Transcripts encoding the
      monkey poliovirus receptors originate from a region analogous to that identified
      for hPVR transcripts.

PMID- 9038167
TI  - T-cell proto-oncogene rhombotin-2 is a complex transcription regulator containing
      multiple activation and repression domains.
AB  - The LIM domain protein rhombotin-2 (RBTN-2/TTG-2/LMO2) is involved in many
      processes, including leukemogenesis and erythropoiesis. It is thought that the
      principle role of RBTN-2 in these processes is to regulate transcription. To
      examine the potential for RBTN-2 to modulate transcription, we constructed RBTN
      2/GAL4 DNA-binding domain fusion proteins and measured their ability to activate
      transcription of a reporter gene construct. From these studies we identified a
      transcription activation domain within the NH2 terminus of RBTN-2. This
      activation domain was further localized within a proline-rich 19-amino acid
      region. A second activation domain of 11 amino acids was also identified. This
      domain was located within the COOH terminus of RBTN-2, and functioned in
      mammalian cells but not in yeast. Furthermore, the two LIM domains of RBTN-2 were
      shown to function as transcription repression domains. Each individual LIM domain
      acted as an independent transcription repression domain on a heterologous
      activation domain. However, in context of full-length RBTN-2, the LIM domains
      selectively repressed the NH2-terminal activation domain, but had no effect on
      the COOH-terminal domain. Overall, these results demonstrate that the T-cell
      oncogene RBTN-2 is a complex transcription factor possessing multiple
      transcription regulatory modules, including two activation domains and two
      repression domains.

PMID- 9038168
TI  - RalGDS functions in Ras- and cAMP-mediated growth stimulation.
AB  - Thyroid-stimulating hormone stimulates proliferation through both the cAMP
      dependent protein kinase and Ras but not through Raf-1 and mitogen-activated and
      extracellular signal-related kinase kinase. We now report that thyroid
      stimulating hormone represses mitogen-activated protein kinase activity and that
      microinjection of an effector domain mutant Ha-Ras protein, Ras(12V,37G),
      defective in Raf-1 binding and mitogen-activated protein kinase activation,
      stimulates DNA synthesis in quiescent and thyroid-stimulating hormone-treated
      thyrocytes. A yeast two-hybrid screen identified RalGDS as a Ras(12V,37G) binding
      protein and therefore a potential effector of Ras in these cells. Associations
      between Ras and RalGDS were observed in extracts prepared from thyroid cells.
      Microinjection of a mutant RalA(28N) protein thought to sequester RalGDS family
      members reduced DNA synthesis stimulated by Ras as well as cAMP-mediated DNA
      synthesis in two cell lines which respond to cAMP with mitogenesis. These results
      support the idea that RalGDS may be an effector of Ras in cAMP-mediated growth
      stimulation.

PMID- 9038169
TI  - A population of rat liver lysosomes responsible for the selective uptake and
      degradation of cytosolic proteins.
AB  - Two populations of rat liver lysosomes can be distinguished on the basis of their
      density. A major difference between these populations is that one contains the
      heat shock cognate protein of 73 kDa (hsc73) within the lysosomal lumen. The
      lysosomal fraction containing hsc73 exhibits much higher efficiencies in the in
      vitro uptake and degradation of glyceraldehyde-3-phosphate dehydrogenase and
      ribonuclease A, two well established substrates of the selective lysosomal
      pathway of intracellular protein degradation. Preloading of the lysosomal
      population that is devoid of lumenal hsc73 with hsc73 isolated from cytosol
      activated the selective transport of substrate proteins into these lysosomes.
      Furthermore, treatment of animals with leupeptin, an inhibitor of lysosomal
      cathepsins, or 88 h of starvation also increased the amount of hsc73 within their
      lysosomal lumen, and these in vivo treatments also activated the selective
      transport of substrate proteins in vitro. Thus, the hsc73 located within
      lysosomes appears to be required for efficient uptake of cytosolic proteins by
      these organelles. The difference in hsc73 content between the lysosomal
      populations appears to be due to differences in their ability to take up hsc73
      combined with differences in the intralysosomal degradation rates of hsc73. The
      increased stability of hsc73 in one population of lysosomes is primarily a
      consequence of this lysosomal population's more acidic pH.

PMID- 9038170
TI  - Monomeric kinesin head domains hydrolyze multiple ATP molecules before release
      from a microtubule.
AB  - Transient kinetic analysis of microtubule-stimulated ATP hydrolysis by the
      monomeric kinesin motor domain DKH357 was performed to investigate the kinetic
      pattern of a monomer. Both ATP and ADP produced dissociation of the complex,
      microtubule (MT).E, of microtubules with DKH357 at a maximum rate of
      approximately 45 s-1 as determined by decrease in turbidity. The maximum
      dissociation rate was independent of the KCl concentration between 25 and 200 mM.
      At subsaturating levels of nucleotide, ATP was more effective than ADP in
      dissociating DKH357 from MT.E (1.6 and 0.4 microM-1 s-1 for ATP and ADP,
      respectively, at 50 mM KCl). Addition of ATP to MT.E results in a burst of
      product formation with a maximum initial rate of approximately 100 s-1 at
      saturating levels of ATP. This maximum hydrolysis rate of 100 s-1 is similar to
      the maximum steady state ATPase rate at saturating microtubules of approximately
      70 s-1, and thus hydrolysis is at least partially rate-limiting. When the MT
      lattice was highly occupied with bound DKH357, the amplitude of the burst was
      approximately 2 per DKH357 active site (superstoichiometric). The rate constant
      for the burst transient was approximately 45 s-1, which is the same as the rate
      for dissociation of DKH357 from the microtubule and this suggests that
      dissociation and termination of the burst phase are coupled. The size of the
      burst increased with decreasing initial occupancy of the MT lattice with bound
      DKH357 and approached the value of approximately 4 ATP molecules predicted by
      previous steady state measurements (Jiang, W., Stock, M., Li, X., and Hackney, D.
      D., submitted for publication).

PMID- 9038171
TI  - Neuronal Cdc2-like kinase (Nclk) binds and phosphorylates the retinoblastoma
      protein.
AB  - The tumor suppressor retinoblastoma protein (RB) plays a central role in cellular
      growth regulation, differentiation, and apoptosis. Phosphorylation of RB results
      in a consequent loss of its ability to inhibit cell cycle progression. However,
      how RB phosphorylation might be regulated in apoptotic or postmitotic cells, such
      as neurons, remains unclear. Here we report that neuronal Cdc2-like kinase
      (Nclk), composed of Cdk5 and a neuronal Cdk5 activator (p25(nck5a)), can bind and
      phosphorylate RB. Since RB has been shown recently to associate with D-type G1
      cyclins and viral oncoproteins through a common peptide sequence motif of LXCXE,
      Nclk binding may be mediated by a related sequence motif (LXCXXE) found in
      p25(nck5a). We demonstrate (i) in vitro binding of bacterially expressed
      p25(nck5a) to a GST-RB fusion protein, (ii) coprecipitation of GST-RB and
      reconstituted Cdk5.p25(nck5a), and (iii) phosphorylation of GST-RB by bacterially
      expressed Cdk5.p25(nck5a) kinase and by Cdk5.p25(nck5a) kinase purified from
      bovine brain. Finally, we show that immunoprecipitation of RB from embryonic
      mouse brain homogenate results in the coprecipitation of Cdk5 and that Cdk5
      kinase activity is maximal during late embryonic development, a period when
      programmed cell death of developing neurons is greatest. Taken together, these
      results suggest that Nclk can bind to and phosphorylate RB in vitro and in vivo.
      We infer that Nclk may play an important role in regulating the activity of RB in
      the brain, including perhaps in apoptosing neurons.

PMID- 9038172
TI  - The human factor H-related protein 4 (FHR-4). A novel short consensus repeat
      containing protein is associated with human triglyceride-rich lipoproteins.
AB  - A novel apoprotein of an apparent molecular mass of 86 kDa in its unreduced form
      was identified in human triglyceride-rich lipoproteins. This protein was purified
      and the amino acid sequence of six proteolytic fragments was found to overlap
      with that of the factor H-related proteins. In parallel we identified the cDNA
      encoding a new complement factor H-related protein, termed FHR-4. The sequences
      of the new apoprotein overlapped with that of the FHR-4 protein. Similar to the
      previously described factor H-related proteins, FHR-4 contains a hydrophobic
      signal sequence followed by a stretch of five repetitive elements termed short
      consensus repeats. Recombinant FHR-4 protein was expressed in the baculovirus
      system and has an apparent molecular mass of 42 kDa. In addition a 84-kDa dimeric
      form of the recombinant FHR-4 was detected. Using an immunoaffinity column with
      antibodies raised against the recombinant FHR-4, we isolated a 86-kDa protein
      from human plasma. The different molecular mass of the recombinant FHR-4 and the
      dimeric FHR-4 in plasma is due to different carbohydrate moieties. The 86-kDa
      plasma protein and the novel apolipoprotein had identical mobility on SDS
      polyacrylamide gel electrophoresis analysis and reacted with antisera raised
      against the reFHR-4 and the purified apoprotein. In conclusion, we have
      identified a novel factor H-related protein, FHR-4, in human plasma and
      demonstrate that this protein is present in triglyceride-rich lipoproteins in a
      dimeric form. This observation provides an intriguing new aspect on possible
      function(s) of this novel protein and the other factor H-related proteins.

PMID- 9038173
TI  - Activation of the adenovirus protease requires sequence elements from both ends
      of the activating peptide.
AB  - The adenovirus protease requires activation by an 11-residue peptide,
      GVQSLKRRRCF, to achieve maximum proteolytic activity. Derived from the C terminus
      of the viral protein pVI, the activating peptide (pVI-CT) forms a disulfide bond
      with cysteine 104 of the protease and causes a conformational change that
      accompanies the development of proteolytic activity. Results presented here show
      that the interaction of pVI-CT with the protease is dependent not only on the
      cysteine 10 but also on glycine 1 and valine 2. Removal of these residues,
      acetylation of the N-terminal glycine, or mutation of the valine to alanine or
      threonine significantly reduces or abolishes activation. Peptides lacking Gly-1
      and Val-2 still form a disulfide bond with the protease but do not cause a
      conformational change in the protease also they are not effective inhibitors of
      activation as the interaction is readily reversed by full-length pVI-CT. These
      results suggest that pVI-CT causes activation by binding to two distinct regions
      of the protease and in doing so stabilizes the catalytic site. The reversible
      nature of the activation, suggested by the results presented here, may well
      reflect an in vivo regulatory mechanism.

PMID- 9038174
TI  - Changing J774A.1 cells to new medium perturbs multiple signaling pathways,
      including the modulation of protein kinase C by endogenous sphingoid bases.
AB  - Sphingosine, sphinganine, and other long-chain (sphingoid) bases are highly
      bioactive intermediates of sphingolipid metabolism that have diverse effects when
      added to cells, including the inhibition of protein kinase C (PKC) as evaluated
      by both enzymatic activity and [3H]phorbol dibutyrate ([3H]PDBu) binding.
      Nonetheless, changes in endogenous sphingoid bases have not been proven to affect
      PKC or other signal transduction pathways. We have discovered recently that
      changing J774A.1 cells to new medium results in up to 10-fold increases in
      sphingoid bases (Smith, E. R., and Merrill, A. H., Jr. (1995) J. Biol. Chem. 270,
      18749-18758); therefore, this system was used to elevate sphingosine and
      sphinganine and determine if PKC was affected. Incubation of J774A.1 cells in new
      medium for 30 min increased the levels of these endogenous sphingoid bases to
      approximately 0.5 nmol/mg of protein and decreased [3H]PDBu binding by 40-60%.
      Addition of NH4Cl, which suppresses the change in sphingosine, restored [3H]PDBu
      binding. Elevation of endogenous sphinganine by a second method (addition of
      fumonisin B1, an inhibitor of ceramide synthase) also reduced [3H]PDBu binding;
      therefore, elevations in sphingosine and sphinganine can both affect PKC. The
      elevation in sphingoid bases was also associated with an increase in the amount
      of PKC-delta (the major PKC isozyme in J774A. 1 cells) in the cytosol, as
      determined by activity assays and immunoblot analyses. Changing the culture
      medium affected other PKC isozymes, increased cellular levels of diacylglycerol,
      dihydroceramide, and ceramide, and altered the expression of two genes (the
      expression of JE was increased, and the induction of MnSOD by TNF-alpha was
      potentiated). Thus, changing the culture medium has numerous effects on J774A.1
      cells, including the modulation of PKC by endogenous sphingoid bases.

PMID- 9038175
TI  - Sequence-specific DNA binding and transcription factor phosphorylation by Ku
      Autoantigen/DNA-dependent protein kinase. Phosphorylation of Ser-527 of the rat
      glucocorticoid receptor.
AB  - NRE1 is a DNA sequence element through which Ku antigen/DNA-dependent protein
      kinase (DNA-PK) catalytic subunit represses the induction of mouse mammary tumor
      virus transcription by glucocorticoids. Although Ku is an avid binder of DNA ends
      and has the ability to translocate along DNA, we report that direct sequence
      specific Ku binding occurs with higher affinity (Kd = 0.84 +/- 0.24 nM) than DNA
      end binding. Comparison of Ku binding to several sequences over which Ku can
      accumulate revealed two classes of sequence. Sequences with similarity to NRE1
      competed efficiently for NRE1 binding. Conversely, sequences lacking similarity
      to NRE1 competed poorly for Ku and were not recognized in the absence of DNA
      ends. Phosphorylation of glucocorticoid receptor (GR) fusion proteins by DNA-PK
      reflected Ku DNA-binding preferences and demonstrated that co-localization of GR
      with DNA-PK on DNA in cis was critical for efficient phosphorylation.
      Phosphorylation of the GR fusion protein by DNA-PK mapped to a single site, Ser
      527. This site occurs adjacent the GR nuclear localization sequence between the
      DNA and ligand binding domains of GR, and thus its phosphorylation, if confirmed,
      has the potential to affect receptor function in vivo.

PMID- 9038176
TI  - Expression of a recombinant apolipoprotein(a) in HepG2 cells. Evidence for
      intracellular assembly of lipoprotein(a).
AB  - Apolipoprotein(a) (apo(a)), a large glycoprotein with extensive homology to
      plasminogen, forms a complex with apolipoprotein B100 (apoB100), which circulates
      in human plasma in the form of lipoprotein(a) (Lp(a)). Evidence indicates that
      the association of apo(a) with apoB100 occurs in the extracellular environment.
      We have reevaluated the possibility that apo(a)-B100 association can also occur
      as an intracellular event through studies with HepG2 cells stably transfected
      with an apo(a) minigene. Several lines of evidence support this possibility.
      First, continued Lp(a) production was demonstrated following incubation of
      transfected HepG2 cells with anti-apo(a) antisera, conditions that effectively
      block the fluid-phase association of apo(a) and apoB100 in vitro. Second, an
      apo(a)-B100 complex was detectable in Western blot analyses of transfected HepG2
      lysates following immunoprecipitation with anti-apo(a) antisera. These studies
      incorporated precautions to eliminate cell-surface attachment of preformed apo(a)
      B100 complexes to the low density lipoprotein receptor and were conducted in the
      presence of the lysine analog epsilon-aminocaproic acid, which precludes apo(a)
      B100 association occurring during the isolation and analyses. Third, the presence
      of an intracellular apo(a)-B100 complex was demonstrated in lipoproteins isolated
      from microsomal contents. Of particular significance was the observation that
      this complex contained the precursor form of apo(a), which is not secreted, in
      addition to the mature, recombinant form. Finally, direct evidence was provided
      for the synthesis of a precursor form of apo(a) in a nascent intracellular
      complex with apoB100 following treatment of transfected HepG2 cells with
      brefeldin A plus N-acetyl-leucyl-leucyl-norleucinal. Taken together, these data
      suggest that apo(a)-B100 association can occur as an intracellular event in a
      human hepatoma-derived cell line, raising important implications for the
      regulation of Lp(a) secretion from human liver.

PMID- 9038177
TI  - Mechanism of Ca2+ and monosaccharide binding to a C-type carbohydrate-recognition
      domain of the macrophage mannose receptor.
AB  - Site-directed mutagenesis has been used to identify residues that ligate Ca2+ and
      sugar to the fourth C-type carbohydrate-recognition domain (CRD) of the
      macrophage mannose receptor. CRD-4 is the only one of the eight CRDs of the
      mannose receptor to exhibit detectable monosaccharide binding when expressed in
      isolation, and it is central to ligand binding by the receptor. CRD-4 requires
      two Ca2+ for sugar binding, like the CRD of rat serum mannose-binding protein
      (MBP-A). Sequence comparisons between the two CRDs suggest that the binding site
      for one Ca2+, which ligates directly to the bound sugar in MBP-A, is conserved in
      CRD-4 but that the auxiliary Ca2+ binding site is not. Mutation of the four
      residues at positions in CRD-4 equivalent to the auxiliary Ca2+ binding site in
      MBP-A indicates that only one, Asn728, is involved in ligation of Ca2+. Alanine
      scanning mutagenesis was used to identify two other asparagine residues and one
      glutamic acid residue that are probably involved in ligation of the auxiliary
      Ca2+ to CRD-4. Sequence comparisons with other C-type CRDs suggest that the
      proposed binding site for the auxiliary Ca2+ in CRD-4 of the mannose receptor is
      unique. Evidence that the conserved Ca2+ in CRD-4 bridges between the protein and
      bound sugar in a manner analogous to MBP-A was obtained by mutation of one of the
      amino acid side chains at this site. Ring current shifts seen in the 1H NMR
      spectra of methyl glycosides of mannose, GlcNAc, and fucose in the presence of
      CRD-4 and site-directed mutagenesis indicate that a stacking interaction with
      Tyr729 is also involved in binding of sugars to CRD-4. This interaction
      contributes about 25% of the total free energy of binding to mannose. C-5 and C-6
      of mannose interact with Tyr729, whereas C-2 of GlcNAc is closest to this
      residue, indicating that these two sugars bind to CRD-4 in opposite orientations.
      Sequence comparisons with other mannose/GlcNAc-specific C-type CRDs suggest that
      use of a stacking interaction in the binding of these sugars is probably unique
      to CRD-4 of the mannose receptor.

PMID- 9038178
TI  - The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced
      enzyme activity and fluconazole resistance through reduced affinity.
AB  - Sterol 14alpha-demethylase (P45051) is the target for azole antifungal compounds,
      and resistance to these drugs and agrochemicals is of significant practical
      importance. We undertook site-directed mutagenesis of the Candida albicans P45051
      heterologously expressed in Saccharomyces cerevisiae to probe a model structure
      for the enzyme. The change T315A reduced enzyme activity 2-fold as predicted for
      the removal of the residue that formed a hydrogen bond with the 3-OH of the
      sterol substrate and helped to locate it in the active site. This alteration
      perturbed the heme environment, causing an altered reduced carbon monoxide
      difference spectrum with a maximum at 445 nm. The changes also reduced the
      affinity of the enzyme for the azole antifungals ketoconazole and fluconazole and
      after expression induced by galactose caused 4-5-fold azole resistance in
      transformants of S. cerevisiae. This is the first example of a single base change
      in the target enzyme conferring resistance to azoles through reduced azole
      affinity.

PMID- 9038179
TI  - Ligand linked assembly of Scapharca dimeric hemoglobin.
AB  - The assembly of Scapharca dimeric hemoglobin as a function of ligation has been
      explored by analytical gel chromatography, sedimentation equilibrium, and oxygen
      binding experiments to test the proposal that its cooperativity is based on
      quaternary enhancement. This hypothesis predicts that the liganded form would be
      assembled more tightly into a dimer than the unliganded form and that
      dissociation would lead to lower oxygen affinity. Our experiments demonstrate
      that although the dimeric interface is quite tight in this hemoglobin,
      dissociation can be clearly detected in the liganded states with monomer to dimer
      association constants in the range of 10(8) M-1 for the CO-liganded state and
      lower association constants measured in the oxygenated state. In contrast, the
      deoxy dimer shows no detectable dissociation by analytical ultracentrifugation.
      Thus, the more highly hydrated deoxy interface of this dimer is also the more
      tightly assembled. Equilibrium oxygen binding experiments reveal an increase in
      oxygen affinity and decrease in cooperativity as the concentration is lowered (in
      the muM range). These experiments unambiguously refute the hypothesis of
      quaternary enhancement and indicate that, as in the case of human hemoglobin and
      other allosteric proteins, quaternary constraint underlies cooperativity in
      Scapharca dimeric hemoglobin.

PMID- 9038180
TI  - The Cre recombinase cleaves the lox site in trans.
AB  - The Cre protein is a conservative site-specific recombinase that is encoded by
      bacteriophage P1. Its function in vivo is to resolve dimeric lysogenic P1
      plasmids that arise by general recombination. In this way Cre facilitates
      effective partition of the P1 prophage. Cre is a member of the integrase family
      of conservative site-specific recombinases. Cleavage of the DNA by the integrases
      involves covalent attachment of a conserved nucleophilic tyrosine to the 3'
      phosphoryl end at the site of the break. We have used in vitro complementation
      tests to show that the Cre protein, like the Flp protein of the 2-microm plasmid
      of Saccharomyces cerevisiae, cleaves its target lox site in trans. Moreover, the
      data are compatible with two modes of cleavage; one requires the reconstitution
      of a pseudo full-site from half-sites and the other requires the assembly of a
      higher order complex that resembles a synaptic complex.

PMID- 9038181
TI  - Identification of functional domains in the neuronal Cdk5 activator protein.
AB  - Cyclin-dependent kinase 5 (Cdk5) is activated by the neuronal-specific activator
      protein, p35. In contrast to the activation of typical CDKs by cyclin subunits,
      p35.Cdk5 was not further activated by the CDK-activating kinase (CAK) and was
      neither phosphorylated nor inhibited by the Tyr-15-specific Wee1 kinase. The
      previously identified proteolytic active fragment of p35, p25 (residues 91-307)
      as well as the slightly smaller fragment containing residues 109-291, was found
      to be sufficient to bind and activate Cdk5. Other CDKs, including Cdk2,
      associated weakly with p25. However, their kinase activity was only activated to
      the low level observed for cyclin A.Cdk2 without Thr-160 phosphorylation, and
      phosphorylation of Thr-160 in Cdk2 did not activate the p25.Cdk2 complex further.
      We have identified distinct regions in p35 required for binding to Cdk5 or
      activation of Cdk5. Residues approximately 150-200 of p35 were sufficient for
      binding to Cdk5, but residues approximately 279-291 were needed in addition for
      activation of Cdk5 in vitro.

PMID- 9038182
TI  - Conformational changes due to membrane binding and channel formation by
      staphylococcal alpha-toxin.
AB  - Conformational changes occurring upon membrane binding and subsequent insertion
      of staphylococcal alpha-toxin were studied using complementary spectroscopic
      techniques. Experimental conditions were established where binding could be
      uncoupled from membrane insertion but insertion and channel formation seemed to
      be concomitant. Binding led to changes in tertiary structure as witnessed by an
      increase in tryptophan fluorescence, a red shift of the tryptophan maximum
      emission wavelength, and a change in the near UV CD spectrum. In contrast to what
      was observed for the soluble form of the toxin, 78% of the tryptophan residues in
      the membrane-bound form were accessible to the hydrophilic quencher KI. At this
      stage, the tryptophan residues were not in the immediate vicinity of the lipid
      bilayer. Upon membrane insertion, a second conformational change occurred
      resulting in a dramatic drop of the near UV CD signal but an increase of the far
      UV signal. Tryptophan residues were no longer accessible to KI but could be
      quenched by brominated lipids. In the light of the available data on channel
      formation by alpha-toxin, our results suggest that the tryptophan residues might
      be dipping into the membrane in order to anchor the extramembranous part of the
      channel to the lipid bilayer.

PMID- 9038184
TI  - Human class Mu glutathione transferases, in particular isoenzyme M2-2, catalyze
      detoxication of the dopamine metabolite aminochrome.
AB  - Human glutathione transferases (GSTs) were shown to catalyze the reductive
      glutathione conjugation of aminochrome (2, 3-dihydroindole-5,6-dione). The class
      Mu enzyme GST M2-2 displayed the highest specific activity (148 micromol/min/mg),
      whereas GSTs A1-1, A2-2, M1-1, M3-3, and P1-1 had markedly lower activities (<1
      micromol/min/mg). The product of the conjugation, with a UV spectrum exhibiting
      absorption peaks at 277 and 295 nm, was 4-S-glutathionyl-5,6-dihydroxyindoline as
      determined by NMR spectroscopy. In contrast to reduced forms of aminochrome
      (leucoaminochrome and o-semiquinone), 4-S-glutathionyl-5, 6-dihydroxyindoline was
      stable in the presence of molecular oxygen, superoxide radicals, and hydrogen
      peroxide. However, the strongly oxidizing complex of Mn3+ and pyrophosphate
      oxidizes 4-S-glutathionyl-5,6-dihydroxyindoline to 4-S-glutathionylaminochrome, a
      new quinone derivative with an absorption peak at 620 nm. GST M2-2 (and to a
      lower degree, GST M1-1) prevents the formation of reactive oxygen species linked
      to one-electron reduction of aminochrome catalyzed by NADPH-cytochrome P450
      reductase. The results suggest that the reductive conjugation of aminochrome
      catalyzed by GSTs, in particular GST M2-2, is an important cellular antioxidant
      activity preventing the formation of o-semiquinone and thereby the generation of
      reactive oxygen species.

PMID- 9038186
TI  - Identification and functional characterization of an active-site lysine in
      mevalonate kinase.
AB  - We report the construction of an expression plasmid for rat mevalonate kinase and
      the overexpression of recombinant enzyme in Escherichia coli. The homogeneous
      enzyme had a specific activity of 30 units/mg and an observed subunit molecular
      mass of 42 kDa. The Michaelis constants (Km) for DL-potassium mevalonate (288
      microM) and for ATP (1.24 mM) were in agreement with values reported for enzymes
      isolated from rat liver (Tanaka, R. D., Schafer, B. L., Lee, L. Y.,
      Freudenberger, J. S., and Mosley, S. T. (1990) J. Biol. Chem. 265, 2391-2398).
      Recombinant rat mevalonate kinase was inactivated by the lysine-specific reagent,
      pyridoxal phosphate (PLP). ATP (5 mM) afforded protection against inactivation,
      suggesting reaction of PLP with an active-site lysine. Mapping, isolation, and
      Edman degradation of the ATP-protectable peptide from [3H]PLP-inactivated
      borohydride-reduced mevalonate kinase allow assignment of lysine 13, a residue
      invariant in known mevalonate kinase sequences, as the modification site. These
      results represent the first identification of an active-site residue in
      mevalonate kinase. The function of lysine 13 was evaluated by replacing this
      residue with methionine. Vm of the mutant protein is diminished by 56-fold,
      suggesting that lysine 13 facilitates catalysis. Kd values of wild-type and
      mutant proteins for ATP were determined in electron spin resonance competition
      experiments. The observed 56-fold diminution in affinity for the mutant enzyme
      supports an additional role for lysine 13 in stabilization of ATP binding.

PMID- 9038185
TI  - A GTPase-activating protein for the G protein Galphaz. Identification,
      purification, and mechanism of action.
AB  - A GTPase-activating protein (GAP) specific for Galphaz was identified in brain,
      spleen, retina, platelet, C6 glioma cells, and several other tissues and cells.
      Gz GAP from bovine brain is a membrane protein that is refractory to
      solubilization with most detergents but was solubilized with warm Triton X-100
      and purified up to 50,000-fold. Activity is associated with at least two separate
      proteins of Mr approximately 22,000 and 28,000, both of which have similar
      specific activities. In an assay that measures the rate of hydrolysis of GTP pre
      bound to detergent-soluble Galphaz, the GAP accelerates hydrolysis over 200-fold,
      from 0.014 to 3 min -1 at 15 degrees C, or to >/=20 min-1 at 30 degrees C. It
      does not alter rates of nucleotide association or dissociation. When co
      reconstituted into phospholipid vesicles with trimeric Gz and m2 muscarinic
      receptor, Gz GAP accelerates agonist-stimulated steady-state GTP hydrolysis as
      predicted by its effect on the hydrolytic reaction. In the single turnover assay,
      the Km of the GAP for Galphaz-GTP is 2 nM. Its activity is inhibited by Galphaz
      guanosine 5'-O-thiotriphosphate (Galphaz-GTPgammaS) or by Galphaz-GDP/AlF4 with
      Ki approximately 1.5 nM for both species; Galphaz-GDP does not inhibit. G protein
      betagamma subunits inhibit Gz GAP activity, apparently by forming a GTP
      Galphazbetagamma complex that is a poor GAP substrate. Gz GAP displays little GAP
      activity toward Galphai1 or Galphao, but its activity with Galphaz is
      competitively inhibited by both Galphai1 and Galphao at nanomolar concentrations
      when they are bound to GTPgammaS but not to GDP. Neither phospholipase C-beta1 (a
      Gq GAP) nor several adenylyl cyclase isoforms display Gz GAP activity.

PMID- 9038187
TI  - Characterization of endogenous neuropeptide Y in rat hippocampus and its
      metabolism by nanospray mass spectrometry.
AB  - Neuropeptide Y (NPY) is a 36-residue-long neuropeptide which has been implicated
      in the regulation of feeding behavior and modulation of the circadian rhythm. We
      identified the primary structure of the endogenous NPY-immunoreactive material in
      the rat hippocampus using a combination of chromatographic techniques and
      nanospray mass spectrometry. The major component in the brain tissue corresponded
      to the authentic amidated form of NPY(1-36). The fate of NPY in the central
      nervous system was studied by subjecting pure peptide to the protease(s) present
      in hippocampal synaptosomes to reveal potential cleavage site(s). NPY was
      efficiently metabolized with a single cleavage between Leu30-Ile31. Thus,
      processing of NPY resulted in formation of the C-terminally truncated fragment
      NPY(1-30) and its counterpart NPY(31-36). The enzyme revealed properties of
      aspartic protease, being blocked by pepstatin and having a pH optimum between 4
      and 5. The data clarify the structure of NPY and its inactivation pathway in the
      brain, which is different from that found in the periphery, and may have
      important consequences in vivo.

PMID- 9038188
TI  - Binding of iodide to Arthromyces ramosus peroxidase investigated with X-ray
      crystallographic analysis, 1H and 127I NMR spectroscopy, and steady-state
      kinetics.
AB  - The site and characteristics of iodide binding to Arthromyces ramosus peroxidase
      were examined by x-ray crystallographic analysis, 1H and 127I NMR, and kinetic
      studies. X-ray analysis of an A. ramosus peroxidase crystal soaked in a KI
      solution at pH 5.5 showed that a single iodide ion is located at the entrance of
      the access channel to the distal side of the heme and lies between the two
      peptide segments, Phe90-Pro91-Ala92 and Ser151-Leu152-Ile153, 12.8 A from the
      heme iron. The distances between the iodide ion and heme peripheral methyl groups
      were all more than 10 A. The findings agree with the results obtained with 1H NMR
      in which the chemical shift and intensity of the methyl groups in the hyperfine
      shift region of A. ramosus peroxidase were hardly affected by the addition of
      iodide, unlike the case of horseradish peroxidase. Moreover, 127I NMR and steady
      state kinetics showed that the binding of iodide depends on protonation of an
      amino acid residue with a pKa of about 5.3, which presumably is the distal
      histidine (His56), 7.8 A away from the iodide ion. The mechanism of electron
      transfer from the iodide ion to the heme iron is discussed on the basis of these
      findings.

PMID- 9038189
TI  - On the unique structural organization of the Saccharomyces cerevisiae pyruvate
      dehydrogenase complex.
AB  - Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of
      the three functional classes of multienzyme complexes that catalyze the oxidative
      decarboxylation of alpha-keto acids, forms the central core to which the other
      components attach. We have determined the structures of the truncated 60-mer core
      dihydrolipoamide acetyltransferase (tE2) of the Saccharomyces cerevisiae pyruvate
      dehydrogenase complex and complexes of the tE2 core associated with a truncated
      binding protein (tBP), intact binding protein (BP), and the BP associated with
      its dihydrolipoamide dehydrogenase (BP.E3). The tE2 core is a pentagonal
      dodecahedron consisting of 20 cone-shaped trimers interconnected by 30 bridges.
      Previous studies have given rise to the generally accepted belief that the other
      components are bound on the outside of the E2 scaffold. However, this
      investigation shows that the 12 large openings in the tE2 core permit the
      entrance of tBP, BP, and BP.E3 into a large central cavity where the BP component
      apparently binds near the tip of the tE2 trimer. The bone-shaped E3 molecule is
      anchored inside the central cavity through its interaction with BP. One end of E3
      has its catalytic site within the surface of the scaffold for interaction with
      other external catalytic domains. Though tE2 has 60 potential binding sites, it
      binds only about 30 copies of tBP, 15 of BP, and 12 of BP.E3. Thus, E2 is unusual
      in that the stoichiometry and arrangement of the tBP, BP, and E3.BP components
      are determined by the geometric constraints of the underlying scaffold.

PMID- 9038190
TI  - Ku selectively transfers between DNA molecules with homologous ends.
AB  - Double strand break repair and V(D)J recombination in mammalian cells require the
      function of the Ku protein complex and the DNA-dependent protein kinase. The DNA
      dependent protein kinase is targeted to DNA through its interaction with the Ku
      protein complex, and thus the specificity of template recognition in the repair
      and recombination reactions depend on Ku. We have studied Ku binding to DNA using
      competitive gel shift analysis. We find that Ku bound to one DNA molecule can
      transfer directly to another DNA molecule when the two DNA molecules have
      homologous ends containing a minimum of four matched bases. This remarkable
      reaction can give a false impression of sequence specificity of Ku DNA binding
      under certain assay conditions. A model is proposed for the DNA binding function
      of Ku on the basis of these results and the discovery of a novel type of DNA-Ku
      complex formed at high Ku/DNA ratios is discussed.

PMID- 9038191
TI  - Subcellular distribution of normal and mutant vitamin D receptors in living
      cells. Studies with a novel fluorescent ligand.
AB  - To understand the subcellular localization of the vitamin D receptor (VDR) and to
      measure VDR content in single cells, we recently developed a fluorescent labeled
      ligand, 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY)-calcitriol. This
      tagged hormone has intact biological activity, high affinity and specific binding
      to the receptor, and enhanced fluorescent emission upon receptor binding. Using
      BODIPY-calcitriol, here we monitored the subcellular distribution of VDR in
      living cultured cells by microscopy. Time course studies showed that an
      equilibrium between the cytoplasmic and nuclear hormone binding developed within
      5 min and was maintained thereafter. We found a substantial proportion of VDR
      residing in the cytoplasm, colocalized with endoplasmic reticulum, the Golgi
      complex, and microtubules. Confocal microscopy clarified the presence of VDR
      within discrete regions of the nucleus and along the nuclear envelope. There was
      no VDR in the plasma membrane. Low affinity BODIPY-calcitriol binding sites were
      in the mitochondria. Mutations in the VDR gene selectively and specifically
      altered BODIPY-calcitriol distribution. Defects in the hormone binding region of
      VDR prevented both nuclear and cytoplasmic hormone binding. Defects in the DNA
      binding region decreased the nuclear retention of VDR and prevented localization
      to nuclear foci. These results with BODIPY-calcitriol reveal cytoplasmic VDR
      localization in living cells and open the possibility of studying the three
      dimensional architecture of intranuclear target sites.

PMID- 9038192
TI  - Cardiotrophin 1 (CT-1) inhibition of cardiac myocyte apoptosis via a mitogen
      activated protein kinase-dependent pathway. Divergence from downstream CT-1
      signals for myocardial cell hypertrophy.
AB  - Cardiac myocyte survival is of central importance in the maintenance of the
      function of heart, as well as in the development of a variety of cardiac
      diseases. To understand the molecular mechanisms that govern this function, we
      characterized apoptosis in cardiac muscle cells following serum deprivation.
      Cardiotrophin 1 (CT-1), a potent cardiac survival factor (Sheng, Z., Pennica, D.,
      Wood, W. I., and Chien, K. R. (1996) Development (Camb.) 122, 419-428), is
      capable of inhibiting apoptosis in cardiac myocytes. To explore the potential
      downstream pathways that might be responsible for this effect, we documented that
      CT-1 activated both signal transducer and activator of transcription 3 (STAT3)-
      and mitogen-activated protein (MAP) kinase-dependent pathways. The transfection
      of a MAP kinase kinase 1 (MEK1) dominant negative mutant cDNA into myocardial
      cells blocked the antiapoptotic effects of CT-1, indicating a requirement of the
      MAP kinase pathway for the survival effect of CT-1. A MEK-specific inhibitor
      (PD098059) (Dudley, D. T., Pang, L., Decker, S.-J., Bridges, A. J., and Saltiel,
      A. R. (1995) Proc. Natl. Acad. Sci. USA 92, 7686-7689) is capable of blocking the
      activation of MAP kinase, as well as the survival effect of CT-1. In contrast,
      this inhibitor did not block the activation of STAT3, nor did it have any effect
      on the hypertrophic response elicited following stimulation of CT-1. Therefore,
      CT-1 promotes cardiac myocyte survival via the activation of an antiapoptotic
      signaling pathway that requires MAP kinases, whereas the hypertrophy induced by
      CT-1 may be mediated by alternative pathways, e.g. Janus kinase/STAT or MEK
      kinase/c-Jun NH2-terminal protein kinase.

PMID- 9038193
TI  - Stimulation of the mitogen-activated protein kinase via the A2A-adenosine
      receptor in primary human endothelial cells.
AB  - Adenosine exerts a mitogenic effect on human endothelial cells via stimulation of
      the A2A-adenosine receptor. This effect can also be elicited by the beta2
      adrenergic receptor but is not mimicked by elevation of intracellular cAMP
      levels. In the present work, we report that stimulation of the A2A-adenosine
      receptor and of the beta2-adrenergic receptor activates mitogen-activated protein
      kinase (MAP kinase) in human endothelial cells based on the following criteria:
      adenosine analogues and beta-adrenergic agonists cause an (i) increase in
      tyrosine phosphorylation of the p42 isoform and to a lesser extent of the p44
      isoform of MAP kinase and (ii) stimulate the phosphorylation of myelin basic
      protein by MAP kinase; (iii) this is accompanied by a redistribution of the
      enzyme to the perinuclear region. Pretreatment of the cells with cholera toxin
      (to down-regulate Gsalpha) abolishes activation of MAP kinase by isoproterenol
      but not that induced by adenosine analogues. In addition, MAP kinase stimulation
      via the A2A-adenosine receptor is neither impaired following pretreatment of the
      cells with pertussis toxin (to block Gi-dependent pathways) nor affected by
      GF109203X (1 microM; to inhibit typical protein kinase C isoforms) nor by a
      monoclonal antibody, which blocks epidermal growth factor-dependent signaling. In
      contrast, MAP kinase activation is blocked by PD 098059, an inhibitor of MAP
      kinase kinase 1 (MEK1) activation, which also blunts the A2A-adenosine receptor
      mediated increase in [3H]thymidine incorporation. Activation of the A2A-adenosine
      receptor is associated with increased levels of GTP-bound p21(ras). Thus, our
      experiments define stimulation of MAP kinase as the candidate cellular target
      mediating the mitogenic action of the A2A-adenosine receptor on primary human
      endothelial cells; the signaling pathway operates via p21(ras) and MEK1 but is
      independent of Gi, Gs, and the typical protein kinase C isoforms. This implies an
      additional G protein which links this prototypical Gs-coupled receptor to the MAP
      kinase cascade.

PMID- 9038194
TI  - The pancreatitis-associated protein I promoter allows targeting to the pancreas
      of a foreign gene, whose expression is up-regulated during pancreatic
      inflammation.
AB  - The pancreatitis-associated protein I (PAP I) is a pancreatic secretory protein
      expressed in pancreas during acute pancreatitis but not in the healthy pancreas.
      The promoter of the PAP I gene thus represents a potential candidate to drive
      expression of therapeutic molecules to the diseased pancreas. In this work, we
      have constructed recombinant adenoviruses harboring the chloramphenicol
      acetyltransferase (CAT) gene driven by several fragments of the PAP I promoter
      and have characterized their properties in vitro and in vivo. In vitro studies
      showed that the transduction of the pancreatic cell line AR-42J with these
      adenoviruses led to low levels of CAT activity in basal conditions. After
      stimulation with a combination of interleukin-6 and dexamethasone or after
      induction of oxidative stress, CAT activity was strongly induced, a
      characteristic of the endogenous PAP I gene. Stimulation was maximal when
      constructs comprised 1253 base pairs of the PAP I promoter, upstream from
      initiation of transcription, and decreased with shorter fragments of 317, 180,
      118 or 61 base pairs. The recombinant adenovirus containing the CAT gene under
      the control of the PAP I promoter fragment (-1253/+10) was also tested in vivo.
      Following administration by intravenous injection into mice, CAT activity was
      measured in several tissues 96 h later. In healthy animals, low but significant
      CAT activity was detected in pancreas, compared with near background values
      observed in the other tissues. When experimental acute pancreatitis was induced,
      CAT expression was strongly enhanced only in pancreas. In control experiments
      with adenoviruses in which the CAT gene was driven by the cytomegalovirus
      promoter, higher levels of expression were observed in all tissues. Expression
      was not modified after induction of acute pancreatitis. In conclusion, this study
      shows that (i) a recombinant adenovirus containing a fragment of the PAP I
      promoter allows specific targeting of a reporter gene to the mouse pancreas and
      (ii) expression of the reporter gene in pancreas is induced during acute
      pancreatitis. Adenovirus-mediated gene therapy of acute pancreatitis is therefore
      conceivable.

PMID- 9038195
TI  - Differential tolerance to DNA polymerization by HIV-1 reverse transcriptase on N6
      adenine C10R and C10S benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide-adducted
      templates.
AB  - To determine the effect of various stereoisomers of benzo[a]pyrene-7,8
      dihydrodiol 9,10-epoxide (BPDE) on translesion bypass by human immunodeficiency
      virus-1 reverse transcriptase and its alpha-helix H mutants, six 33-mer templates
      were constructed bearing site- and stereospecific adducts. This in vitro model
      system was chosen to understand the structure-function relationships between the
      polymerase and damaged DNA during replication. Comparison of the replication
      pattern between wild type human immunodeficiency virus-1 reverse transcriptase
      and its mutants, using primers which were 3' to the lesion, revealed essentially
      similar patterns. While these primers terminated with all three of the C10R and
      two of the C10S BPDE-adducted templates 1 base 5' and 1 base 3' to the damaged
      site respectively, (+)-anti-trans-(C10S) BPDE-adducted DNA alone permitted the
      formation of full-length products. Utilization of a primer with its 3'-hydroxyl 1
      base beyond the lesion resulted in full-length products with all the C10S BPDE
      adducted templates and the (-)-syn-trans-(C10R)-BPDE-adducted template, following
      replication with either the wild type or mutant enzymes. However, the other two
      C10R BPDE-adducted templates failed to allow any primer extension, even with the
      wild type enzyme. Although T.P depletion studies further confirmed the
      differential primer extension abilities using the C10R and C10S adducted
      templates, their binding affinities were similar, yet distinct from the
      unadducted template.

PMID- 9038196
TI  - Increased uptake and accumulation of vitamin C in human immunodeficiency virus 1
      infected hematopoietic cell lines.
AB  - Vitamin C (ascorbic acid) is required for normal host defense and functions
      importantly in cellular redox systems. To define the interrelationship between
      human immunodeficiency virus (HIV) infection and vitamin C flux at the cellular
      level, we analyzed vitamin C uptake and its effects on virus production and
      cellular proliferation in HIV-infected and uninfected human lymphoid, myeloid,
      and mononuclear phagocyte cell lines. Chronic or acute infection of these cell
      lines by HIV-1 led to increased expression of glucose transporter 1, associated
      with increased transport and accumulation of vitamin C. Infected cells also
      showed increased transport of glucose analogs. Exposure to vitamin C had a
      complex effect on cell proliferation and viral production. Low concentrations of
      vitamin C increased or decreased cell proliferation depending on the cell line
      and either had no effect or caused increased viral production. Exposure to high
      concentrations of vitamin C preferentially decreased the proliferation and
      survival of the HIV-infected cells and caused decreased viral production. These
      findings indicate that HIV infection in lymphocytic, monocytic, and myeloid cell
      lines leads to increased expression of glucose transporter 1 and consequent
      increased cellular vitamin C uptake. High concentrations of vitamin C were
      preferentially toxic to HIV-infected host defense cell lines in vitro.

PMID- 9038197
TI  - Segments in the C-terminal folding domain of lipoprotein lipase important for
      binding to the low density lipoprotein receptor-related protein and to heparan
      sulfate proteoglycans.
AB  - Lipoprotein lipase (LpL) can mediate cellular uptake of chylomicron and VLDL
      remnants via binding to heparan sulfate proteoglycans (HSPG) and the endocytic
      alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein
      (alpha2MR/LRP). Whereas it is established that the C-terminal folding domain
      binds to alpha2MR/LRP, it remains uncertain whether it binds to heparin and to
      HSPG. To identify segments important for binding to alpha2MR/LRP and to clarify
      possible binding to heparin, we produced constructs of the human C-terminal
      folding domain, LpL-(313-448), and of the fragment LpL-(347-448) in Escherichia
      coli. In addition to binding to alpha2MR/LRP, LpL-(313-448) displayed binding to
      heparin with an affinity similar to that of the LpL monomer, whereas it bound
      poorly to lipoprotein particles. Moreover, LpL-(313-448) displayed heparin
      sensitive binding to normal, but not to HSPG deficient Chinese hamster ovary
      cells. LpL-(313-448) and LpL-(347-448) showed similar affinities for binding to
      both purified alpha2MR/LRP and to heparin. Deletion of LpL residues 380-384
      abolished the binding to LRP, whereas binding to heparin was unperturbed. The
      binding to both heparin and alpha2MR/LRP was essentially abolished following
      deletion of residues 404-430, and pretreatment of CHO cells with the peptide
      comprising aa 402-423 inhibited the binding of LpL-(313-448). We conclude that
      the C-terminal folding domain of human LpL has a site for binding to heparin and
      to HSPG, presumably involving amino acids within residues 404-430. Two segments
      of the domain are necessary for efficient binding to alpha2MR/LRP, one comprising
      residues 380-384 and another overlapping the segment important for binding to
      heparin.

PMID- 9038198
TI  - Molecular mechanisms of doxorubicin-induced cardiomyopathy. Selective suppression
      of Reiske iron-sulfur protein, ADP/ATP translocase, and phosphofructokinase genes
      is associated with ATP depletion in rat cardiomyocytes.
AB  - Doxorubicin, a cardiotoxic antineoplastic, disrupts the cardiac-specific program
      of gene expression (Kurabayashi, M., Dutta, S., Jeyaseelan, R., and Kedes, L.
      (1995) Mol. Cell. Biol. 15, 6386-6397). We have now identified neonatal rat
      cardiomyocyte mRNAs rapidly sensitive to doxorubicin, or its congener daunomycin,
      including transcripts of nuclear genes encoding enzymes critical in production of
      energy in cardiomyocytes: ADP/ATP translocase, a heart- and muscle-specific
      isoform; Reiske iron-sulfur protein (RISP), a ubiquitously expressed electron
      transport chain component; and a muscle isozyme of phosphofructokinase. Loss of
      these mRNAs following doxorubicin or daunomycin is evident as early as 2 h and
      precedes significant reduction of intracellular ATP. ATP levels in control
      cardiomyocytes (17.9 +/- 2.9 nM/mg of protein) fall only after 14 h and reach
      residual levels of 10.4 +/- 0.9 nM (doxorubicin; p = <0.006) and 6.7 +/- 1.9 nM
      (daunomycin; p = <0. 001) by 24 h. Loss of mRNAs generating ATP was highly
      selective since mRNAs for other energy production enzymes, (cytochrome c,
      cytochrome b, and malate dehydrogenase), and genes important in glycolysis
      (pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase) were unaffected
      even at 24 and 48 h. The drugs had no effect on levels of ubiquitously expressed
      RISP mRNA in fibroblasts. These findings could link doxorubicin-induced damage to
      membranes and signaling pathways with 1) suppression of transcripts encoding
      myofibrillar proteins and proteins of energy production pathways and 2) depletion
      of intracellular ATP stores, myofibrillar degeneration, and related cardiotoxic
      effects.

PMID- 9038199
TI  - Pombe Cdc5-related protein. A putative human transcription factor implicated in
      mitogen-activated signaling.
AB  - The Schizosaccharomyces pombe cdc5 gene product is a cell cycle regulator that
      exerts its effects at the G2/M transition in fission yeast. We describe the
      cloning of a putative human transcription factor, pombe Cdc5-related protein
      (PCDC5RP), which bears significant homology to S. pombe Cdc5 and to expressed
      sequences in mouse, nematode, and budding yeast. PCDC5RP is expressed widely in
      normal adult human tissues and thus may have an important general function that
      has been preserved evolutionarily. PCDC5RP contains two tandem repeats of a helix
      turn-helix DNA binding motif, four consensus nuclear localization signals, and a
      hydrophilic, proline-rich central region similar to the transcriptional
      activating domain in Myb family members. Remarkably, PCDC5RP moved rapidly from
      cytoplasm to nucleus upon serum stimulation of cultured cells. This movement
      correlated temporally with an increase in PCDC5RP phosphorylation. Thus, PCDC5RP
      is a presumed transcription factor that appears to transduce cytoplasmic signals
      to the nucleus upon serum stimulation.

PMID- 9038200
TI  - TOUSLED is a nuclear serine/threonine protein kinase that requires a coiled-coil
      region for oligomerization and catalytic activity.
AB  - The TOUSLED (TSL) gene is essential for the proper morphogenesis of leaves and
      flowers in Arabidopsis thaliana. Protein sequence analysis predicts TSL is
      composed of a carboxyl-terminal protein kinase catalytic domain and a large amino
      terminal regulatory domain. TSL fusion proteins, expressed in and purified from
      yeast, were used to demonstrate TSL protein kinase activity in vitro. TSL trans
      autophosphorylates on serine and threonine residues, and phosphorylates exogenous
      substrates. Using the yeast two-hybrid system, TSL was found to oligomerize via
      its NH2-terminal domain. A deletion series indicates that a region containing two
      alpha-helical segments predicted to participate in a coiled-coil structure is
      essential for oligomerization. TSL localizes to the nucleus in plant cells
      through an essential NH2-terminal nuclear localization signal; however, this
      signal is not necessary for protein kinase activity. Finally, deletion mutants
      demonstrate a strict correlation between catalytic activity and the ability to
      oligomerize, arguing that activation of the protein kinase requires interaction
      between TSL molecules.

PMID- 9038201
TI  - Molecular cloning of a novel human CC chemokine liver and activation-regulated
      chemokine (LARC) expressed in liver. Chemotactic activity for lymphocytes and
      gene localization on chromosome 2.
AB  - Partial overlapping cDNA sequences likely to encode a novel human CC chemokine
      were identified from the GenBank Expressed Sequence Tag data base. Using these
      sequences, we isolated full-length cDNA encoding a protein of 96 amino acid
      residues with 20-28% identity to other CC chemokines. By Northern blot, this
      chemokine was mainly expressed in liver among various tissues and strongly
      induced in several human cell lines by phorbol myristate acetate. We thus
      designated this chemokine as LARC from Liver and Activation-Regulated Chemokine.
      We mapped the LARC gene close to the chromosomal marker D2S159 at chromosome 2q33
      q37 by somatic cell and radiation hybrid mappings and isolated two yeast
      artificial chromosome clones containing the LARC gene from this region. To
      prepare LARC, we subcloned the cDNA into a baculovirus vector and expressed it in
      insect cells. The secreted protein started at Ala-27 and was significantly
      chemotactic for lymphocytes. At a concentration of 1 microg/ml, it also showed a
      weak chemotactic activity for granulocytes. Unlike other CC chemokines, however,
      LARC was not chemotactic for monocytic THP-1 cells or blood monocytes. LARC
      tagged with secreted alkaline phosphatase-(His)6 bound specifically to
      lymphocytes, the binding being competed only by LARC and not by other CC or CXC
      chemokines. Scatchard analysis revealed a single class of receptors for LARC on
      lymphocytes with a Kd of 0.4 nM and 2100 sites/cell. Collectively, LARC is a
      novel CC chemokine, which may represent a new group of CC chemokines localized on
      chromosome 2.

PMID- 9038202
TI  - Expression of the rat m4 muscarinic acetylcholine receptor gene is regulated by
      the neuron-restrictive silencer element/repressor element 1.
AB  - Neuronal cell-specific expression of the rat m4 muscarinic acetylcholine receptor
      (mAChR) is regulated by a silencer element. A likely mediator of this silencing
      is the neuron-restrictive silencer element/repressor element 1 (NRSE/RE1), which
      is present 837 base pairs (bp) upstream from the transcription initiation site of
      the m4 mAChR gene (Wood, I. C., Roopra, A., Harrington, C., and Buckley, N. J.
      (1995) J. Biol. Chem. 270, 30933-30940; Mieda, M., Haga, T., and Saffen, D. W.
      (1996) J. Biol. Chem. 271, 5177-5182). In the present study, we examined whether
      this putative NRSE/RE1 functions as a silencer. Transient expression assays using
      m4 mAChR promoter/luciferase expression vectors showed that the m4 NRSE/RE1 is
      necessary and sufficient to repress m4 promoter activity in non-neuronal L6
      cells. m4 promoter activity was only partially repressed, however, in neuronal
      NG108-15 cells exogenously expressing the neuronal-restrictive silencer
      factor/RE1-silencing transcription factor (NRSF/REST). By contrast, the promoter
      activity of the type II sodium channel (NaII) gene was nearly completely
      repressed in NRSF/REST-expressing NG108-15 cells. Experiments with expression
      vectors containing chimeric promoters revealed that the NRSE/RE1 elements derived
      from both the m4 and NaII genes are independently sufficient to silence NaII gene
      promoter activity, but only partially repress m4 mAChR gene promoter activity in
      NRSF/REST-expressing NG108-15 cells. Thus, the repression activity of NRSF/REST
      depends upon the species of promoter to which it is linked. Gel-shift assays
      showed that the NRSF/REST is the only protein that binds to a 92-bp segment from
      the m4 mAChR promoter containing NRSE/RE1. This and the fact that m4 promoter
      activity was completely repressed in L6 cells suggest that the proteins that bind
      to the m4 constitutive promoter may be different from those in NG108-15 cells.
      Deletion analysis of the m4 constitutive promoter revealed that a 90-bp segment
      immediately upstream from the transcription initiation site contains significant
      promoter activity. Gel-shift assays revealed that several proteins in nuclear
      extracts prepared from L6 and NG108-15 cells bind to this 90-bp segment and that
      some of these proteins are L6 or NG108-15 cell-specific. These data support the
      idea that the repression activity of NRSF/REST depends upon the species of
      promoter to which it is linked and upon the proteins that bind to those
      promoters.

PMID- 9038203
TI  - A novel interaction between the juxtamembrane region of the p55 tumor necrosis
      factor receptor and phosphatidylinositol-4-phosphate 5-kinase.
AB  - Tumor necrosis factor-alpha (TNF-alpha) binding to its receptors leads to a
      diversity of biological responses. The actions of TNF are the result of the
      interaction of cytoplasmic proteins that bind directly to the intracellular
      domains of the two TNF receptors, p55 and p75. Here we report a novel interaction
      between the juxtamembrane region of the p55 TNF receptor and a newly discovered
      47-kDa isoform of phosphatidylinositol-4-phosphate 5-kinase (PIP5K), a member of
      the enzyme family that generates the key signaling messenger,
      phosphatidylinositol 4,5-bisphosphate. The interaction was found to be specific
      for the p55 TNF receptor and was not observed with the p75 TNF receptor, the Fas
      antigen, or the p75 neurotrophin receptor, which are other members of the TNF
      receptor superfamily. In vitro experiments using recombinant fusion proteins
      verify the authenticity of the interaction between the p55 receptor and
      PIP5KIIbeta, a new isoform of PIP5K, but not the previously identified 53-kDa
      PIP5KIIalpha. Treatment of HeLa cells with TNF-alpha resulted in an increased
      PIP5K activity. These results indicate that phosphatidylinositol turnover may be
      linked to stimulation of the p55 TNF receptor and suggest that a subset of TNF
      responses may result from the direct association of PIP5KIIbeta with the p55 TNF
      receptor.

PMID- 9038204
TI  - Role of positive and negative cis-regulatory elements in the transcriptional
      activation of the lysozyme locus in developing macrophages of transgenic mice.
AB  - Expression of the chicken lysozyme locus in macrophages is regulated by at least
      six different positive and negative cis-regulatory elements. Chromatin of the
      chicken lysozyme locus is gradually reorganized during macrophage
      differentiation, indicating that each cis-regulatory element is activated at a
      different developmental stage. Irrespective of their differential developmental
      activation, individual cis-regulatory regions are capable of driving
      transcription of the lysozyme gene in mature macrophages of transgenic mice. In
      order to examine the role of different cis-regulatory regions in lysozyme locus
      activation, we analyzed the time course of transcriptional up-regulation of
      deletion mutants of the lysozyme locus in a new in vitro differentiation system
      based on enriched primary macrophage precursor cells from the bone marrow of
      transgenic mice. We show that constructs carrying cis-regulatory elements which
      are structurally reorganized early in development are also transcriptionally
      active at an early stage. A construct in which the early enhancer has been
      deleted shows a delay in transcriptional activation. The presence or absence of a
      negative regulatory element has no influence on the time course of
      transcriptional activation of the lysozyme locus.

PMID- 9038205
TI  - Short hydrophobic segments in the mature domain of ProOmpA determine its stepwise
      movement during translocation across the cytoplasmic membrane of Escherichia
      coli.
AB  - Based on the finding that a series of engineered proOmpAs containing disulfide
      bridged loops of different sizes at different positions exhibits a discontinuous
      mode of polypeptide transit across the cytoplasmic membrane of Escherichia coli,
      we suggested previously that the translocation of preproteins takes place at
      every 30 amino acid residues (Uchida, K., Mori, H., and Mizushima, S. (1995) J.
      Biol. Chem. 270, 30862-30868). In the present study, we investigated the
      molecular mechanism underlying this stepwise translocation. Deletion or
      relocation of hydrophobic segments of the mature domain of proOmpA (H1, residues
      233-237; H2, residues 261-265) significantly altered the pattern of the stepwise
      translocation. The stepwise mode of polypeptide insertion was also observed with
      reconstituted proteoliposomes comprising purified SecA, SecY, and SecE. Cross
      linking experiments involving a photoactivable cross-linker revealed that SecY
      and SecA are the components which interact with the hydrophobic segment of
      proOmpA. The present results indicate that the hydrophobic segments of the mature
      domains of preproteins interact with membrane embedded translocase during
      polypeptide transit across the membrane, which causes a discontinuous mode of
      polypeptide movement.

PMID- 9038206
TI  - Casein kinase II binds to and phosphorylates cytoplasmic dynein.
AB  - We have isolated a 27-kDa protein that binds to cytoplasmic dynein.
      Microsequencing of a 17-amino acid peptide of this polypeptide yielded a sequence
      which completely matched the predicted sequence of the beta subunit of casein
      kinase II, a highly conserved serine/threonine kinase. Affinity chromatography
      using a dynein column indicates that both the alpha and beta subunits of casein
      kinase II are retained by the column from rat brain cytosol. Although dynactin is
      also bound to the column, casein kinase II is not a dynactin subunit. Casein
      kinase II does not co-immunoprecipitate with dynactin, and it binds to a dynein
      intermediate chain column which has been preblocked with excess p150(Glued), a
      treatment that inhibits the binding of dynactin from cytosol. Bacterially
      expressed and purified rat dynein intermediate chain can be phosphorylated by
      casein kinase II in vitro. Further, native cytoplasmic dynein purified from rat
      brain can also be phosphorylated by casein kinase II in vitro. We propose that
      CKII may be involved in the regulation of dynein function possibly by altering
      its cargo specificity or its ability to interact with dynactin.

PMID- 9038207
TI  - Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by
      reverse transcriptases and mammalian DNA polymerases.
AB  - We have measured the efficiencies of utilization of 8-oxo-dGTP and 8-NH2-dGTP by
      human immunodeficiency virus type 1 and murine leukemia virus reverse
      transcriptases and compared them to those of DNA polymerases alpha and beta.
      Initially, we carried out primer extension reactions in the presence of dGTP or a
      dGTP analog and the remaining three dNTPs using synthetic DNA and RNA templates.
      These assays revealed that, in general, 8-NH2-dGTP is incorporated and extended
      more efficiently than 8-oxo-dGTP by all enzymes tested. Second, we determined
      rate constants for the incorporation of each analog opposite a template cytidine
      residue using steady state single nucleotide extension kinetics. Our results
      demonstrated the following. 1) Both reverse transcriptases incorporate the
      nucleotide analogs; discrimination against their incorporation is a function
      primarily of Km or Vmax depending on the analog and the enzyme. 2) Discrimination
      against the analogs is more stringent with the DNA template than with a
      homologous RNA template. 3) Polymerase alpha exhibits a mixed kinetic phenotype,
      with a large discrimination against 8-oxo-dGTP but a comparatively higher
      preference for 8-NH2-dGTP. 4) Polymerase beta incorporates both analogs
      efficiently; there is no discrimination with respect to Km and a significantly
      lower discrimination with respect to Vmax when compared with the other
      polymerases.

PMID- 9038208
TI  - Regulation of murine cytochrome oxidase Vb gene expression in different tissues
      and during myogenesis. Role of a YY-1 factor-binding negative enhancer.
AB  - The mouse cytochrome oxidase (COX) Vb promoter contains three sequence motifs
      with partial or full consensus for YY-1 and GTG factor binding and a CArG box,
      located between positions -480 and -390. Individually, all three motifs
      stimulated transcription of the TKCAT promoter, and bound distinctly different
      proteins from the liver and differentiated C2C12 nuclear extracts. Collectively,
      these motifs, together with the downstream flanking sequence, -378 to -320,
      suppressed the transcription activity of heterologous promoters, thymidine kinase
      chloramphenicol acetyltransferase (TKCAT) and COXIV/CAT. The transcription
      activities of both TKCAT and COXIV/CAT constructs were induced 3-4-fold during
      induced myogenesis of C2C12 cells. The downstream CArG-like motif binds
      transcription factor YY-1, while the upstream YY-1-like motif binds to a yet
      unidentified factor. Co-expression with intact YY-1, but not that lacking the DNA
      binding domain suppressed the transcriptional activity. Mutations targeted to the
      CArG-like motif abolished the suppressive effect of the negative enhancer and the
      inducibility of the promoter during myogenic differentiation. Our results suggest
      that the activity of the negative enhancer may determine the level of expression
      of the COX Vb gene in different tissues.

PMID- 9038209
TI  - Identification of the in vivo phosphorylation sites for acidic-directed kinases
      in murine mdr1b P-glycoprotein.
AB  - P-glycoprotein, the multidrug resistance transporter, is phosphorylated in vivo
      and the major phosphorylation domain has been identified as the linker region
      (amino acids 629-686). The linker region is a highly charged segment of the
      transporter in which the negative and positive amino acid side chains are
      spatially segregated. Both of these charged domains contain several consensus
      phosphorylation sites for protein kinases. Three of the consensus phosphorylation
      sites for basic-directed kinases in murine mdr1b P-glycoprotein are utilized in
      vivo and have been identified as serines 665, 669, and 681. Mutagenesis of all
      the consensus basic-directed kinase phosphorylation sites in the linker region of
      human MDR1 P-glycoprotein did not alter the ability of the mutated transporter to
      confer the multidrug resistance phenotype in stably transfected cell lines. These
      studies would suggest that phosphorylation/dephosphorylation within the basic
      domain of the linker region is not directly involved in regulation of drug
      transporter activity. We now report that the linker region of mdr1b P
      glycoprotein is also phosphorylated in vivo within the acidic domain (amino acids
      631-658). These sites have been mapped using casein kinase II, a prototypic
      acidic-directed kinase, and a recombinant mdr1b linker region peptide (amino
      acids 621-687). Electrospray mass spectrometry demonstrated that casein kinase II
      could introduce up to five phosphates into the recombinant peptide. Two
      dimensional phosphopeptide mapping indicated that all the phosphates were
      contained in a tryptic peptide consisting of amino acids 631-658. Phosphopeptide
      mapping of in vivo labeled P-glycoprotein, isolated from either J7.V1-1, a murine
      vinblastine-resistant cell line, or HeLa cells stably transfected with mdr1b P
      glycoprotein cDNA, revealed that this tryptic peptide was phosphorylated in both
      proteins.

PMID- 9038210
TI  - Direct association of Csk homologous kinase (CHK) with the diphosphorylated site
      Tyr568/570 of the activated c-KIT in megakaryocytes.
AB  - The Csk homologous kinase (CHK), formerly MATK, has previously been shown to bind
      to activated c-KIT. In this report, we characterize the binding of SH2(CHK) to
      specific phosphotyrosine sites on the c-KIT protein sequence. Phosphopeptide
      inhibition of the in vitro interaction of SH2(CHK)-glutathione S-transferase
      fusion protein/c-KIT from SCF/KL-treated Mo7e megakaryocytic cells indicated that
      two sites on c-KIT were able to bind SH2(CHK). These sites were the Tyr568/570
      diphosphorylated sequence and the monophosphorylated Tyr721 sequence. To confirm
      this, we precipitated native CHK from cellular extracts using phosphorylated
      peptides linked to Affi-Gel 15. In addition, purified SH2(CHK)-glutathione S
      transferase fusion protein was precipitated with the same peptide beads. All of
      the peptide bead-binding studies were consistent with the direct binding of
      SH2(CHK) to phosphorylated Tyr568/570 and Tyr721 sites. Binding of FYN and SHC to
      the diphosphorylated Tyr568/570 site was observed, while binding of Csk to this
      site was not observed. The SH2(CHK) binding to the two sites is direct and not
      through phosphorylated intermediates such as FYN or SHC. Site-directed
      mutagenesis of the full-length c-KIT cDNA followed by transient transfection
      indicated that only the Tyr568/570, and not the Tyr721, is able to bind SH2(CHK).
      This indicates that CHK binds to the same site on c-KIT to which FYN binds,
      possibly bringing the two into proximity on associated c-KIT subunits and leading
      to the down-regulation of FYN by CHK.

PMID- 9038211
TI  - Post-translational processing in the Golgi plays a critical role in the
      trafficking of the luteinizing hormone/human chorionic gonadotropin receptor to
      the cell surface.
AB  - Point mutations in the luteinizing hormone/human chorionic gonadotropin (LH/hCG)
      receptor have been shown to cause constitutive activation which results in
      precocious puberty in affected males. We introduced one of these mutations, Asp
      556 --> Gly, into the rat LH/hCG receptor and demonstrated that the mutant
      receptor constitutively activated adenylate cyclase in transfected 293 T cells.
      The cell surface expression of the mutant receptor was lower than that of the
      wild type receptor. Pulse-chase studies showed that the 73-kDa precursor of both
      the mutant and wild type receptors was synthesized at comparable efficiencies.
      However, post-translational processing of the mutant receptor to the mature 92
      kDa form, which has N-linked complex type oligosaccharide chains, was impaired.
      Sensitivity of the mutant receptor to peptide-N-glycanase F and endoglycosidase
      H, and insensitivity to sialidase indicated that the 73-kDa species represents
      the high mannose form that has not yet been trafficked through the medial and
      trans Golgi. Additionally, although the wild type receptor was palmitoylated, the
      mutant receptor was not. Although the high mannose 73-kDa species is capable of
      binding LH/hCG, our results show that post-translational processing in the Golgi
      is required for the mature 92-kDa receptor to reach the cell surface.

PMID- 9038212
TI  - Characterization of downstream Ras signals that induce alternative protease
      dependent invasive phenotypes.
AB  - Invasive and metastatic cells require protease expression for migration through
      the extracellular matrix. Metastatic NIH 3T3 fibroblasts transformed by different
      activated ras genes showed two different protease phenotypes, rasuPA+/CL- and
      rasCL+/uPA- (Zhang, J-Y., and Schultz, R. M. (1992) Cancer Research 52, 6682
      6689). Phenotype rasuPA+/CL- is dependent on expression of the serine-type
      protease urokinase plasminogen activator (uPA) and the phenotype rasCL+/uPA- on
      the cystine-type protease cathepsin L (CL) for lung colonization in experimental
      metastasis. The existence of multiple invasive phenotypes on ras-isoform
      transformation implied the activation of alternative pathways downstream from
      Ras. We now show that c-Raf-1, extracellular signal-regulated protein kinase
      (ERK)-1, and ERK-2 are hyperphosphorylated, and the ERK activity is high in both
      the uPA- and CL-dependent ras-transformed invasive phenotypes. Levels of c-Jun
      and c-Jun NH2-terminal kinase (JNK) activity are also high in the uPA-dependent
      phenotype, but they are almost undetectable in the CL-dependent phenotype. The
      uPA Ras-response element is a PEA3/URTF element, and mobility shift assays show a
      strong PEA3/URTF protein band in the uPA-dependent phenotype. This band is
      competed by a consensus AP-1 DNA sequence and by antibodies to PEA3 and c-Jun.
      Thus, the uPA-invasive phenotype appears to require the activation of Ets/PEA3
      and c-Jun transcription factors activated by the ERK and JNK pathways, while the
      CL-invasive phenotype appears to require ERK activity with suppression of JNK and
      c-Jun activities. These postulates are supported by the introduction of a
      dominant negative c-Jun, TAM67, into cells of phenotype rasuPA+/CL-, which down
      regulated the high uPA mRNA levels characteristic of this phenotype to basal
      levels and up-regulated basal levels of CL mRNA to levels similar to those
      observed in cells of phenotype rasCL+/uPA-. We conclude that the JNK pathway acts
      as a switch between two distinct protease phenotypes that are redundant in their
      abilities to grow tumors and metastasize.

PMID- 9038213
TI  - Nerve growth factor up-regulates the N-methyl-D-aspartate receptor subunit 1
      promoter in PC12 cells.
AB  - The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays important
      roles in synaptic plasticity, the induction of long term potentiation, and
      excitotoxicity. Mechanisms governing the regulation of expression of its subunit
      genes remain largely unknown. The promoter of the essential subunit of the NMDA
      receptor heteromer, NMDAR1, contains DNA binding elements recognized by the nerve
      growth factor-inducible/early growth reaction factor (NGFI/Egr) family of
      transcription factors that are rapidly induced by neurotrophins, such as nerve
      growth factor (NGF). This study examined the effect of NGF on the activity of the
      N-methyl-D-aspartate receptor subunit 1 (NMDAR1) promoter/luciferase reporter
      constructs in PC12 cells, which contain the high affinity TrkA receptor for NGF
      and the low affinity p75(NTR) receptor for neurotrophins. NGF up-regulated the
      activity of the NMDAR1 promoter by 3-4-fold in a time- and dose-dependent manner.
      5' deletional analysis of the promoter indicated that the responsive element(s)
      resides in the proximal region containing GSG and Sp1 sites. Mutational analysis
      of these sites revealed that both were important for NGF regulation. Transient
      expression of Egr-1 increased activity of the wild type promoter but failed to
      increase activity of a GSG mutant promoter. Other neurotrophins did not activate
      the promoter, while K-252a inhibited the action of NGF. These results suggest
      that the NGF effect is mediated by the high affinity NGF receptor, Trk A and that
      neurotrophin binding to the low affinity neurotrophin receptor, p75(NTR), alone
      does not affect the promoter activity. Our results suggest that NGF is able to up
      regulate the activity of the NMDAR1 promoter and may play a role in controlling
      the expression levels of NMDA receptors.

PMID- 9038214
TI  - Template recognition and ribonucleotide specificity of the DNA primase of
      bacteriophage T7.
AB  - The 63-kDa gene 4 DNA primase of phage T7 catalyzes the synthesis of
      oligoribonucleotides on single-stranded DNA templates. At the sequence, 5'-GTC
      3', the primase synthesizes the dinucleotide pppAC; the cytidine residue of the
      recognition sequence is cryptic. Only tetraribonucleotides function as primers,
      but the specificity for the third and fourth position is not as stringent with a
      preference of CMP > AMP >> UMP > GMP. The predominant recognition sites on M13
      DNA are 5'-(G/T)GGTC-3' and 5'-GTGTC-3'. Synthesis is usually limited to
      tetranucleotides, but T7 primase can synthesize longer oligoribonucleotides on
      templates containing long stretches of guanosine residues 5' to the recognition
      sequence. The specificity beyond the first two positions of the primer increases
      as the length of the template on the 3'-side of 5'-GTC-3' increases. On an
      oligonucleotide having 20 3'-flanking cytidine residues GMP is incorporated at
      the third position; incorporation is reduced 4-fold when the flanking sequence
      reaches 65 residues, and little is incorporated on M13 templates. The presence of
      the 56-kDa gene 4 helicase decreases the incorporation of GMP on long templates.
      We propose that pausing is required for the incorporation of less preferred
      nucleotides and that pausing is decreased by the ability of the primase to
      translocate 5' to 3' on templates having long 3'-flanking sequences.

PMID- 9038215
TI  - Activation of cytosolic phospholipase A2 by platelet-derived growth factor is
      essential for cyclooxygenase-2-dependent prostaglandin E2 synthesis in mouse
      osteoblasts cultured with interleukin-1.
AB  - The synthesis of prostaglandins (PGs) is regulated by the arachidonic acid
      release by phospholipase A2 (PLA2) and its conversion to PGs by cyclooxygenase
      (COX). In the present study, we examined the regulation of PG synthesis by
      interleukin (IL)-1alpha in primary mouse osteoblastic cells isolated from mouse
      calvaria. Although IL-1alpha greatly enhanced cox-2 mRNA expression and its
      protein levels, PGE2 was not produced until 24 h. When arachidonic acid was added
      to osteoblastic cells precultured with IL-1alpha for 24 h, PGE2 was produced
      within 10 min. Of several growth factors tested, platelet-derived growth factor
      (PDGF) specifically initiated the rapid synthesis of PGE2, which was markedly
      suppressed by a selective inhibitor of cox-2 (NS-398). In mouse osteoblastic
      cells, cytosolic PLA2 (cPLA2) mRNA and its protein were constitutively expressed
      and increased approximately 2-fold by IL-1alpha, but secretory PLA2 mRNA was not
      detected. PDGF rapidly stimulated PLA2 activity, which was blocked completely by
      a cPLA2 inhibitor (arachidonyltrifluoromethyl ketone). The PDGF-induced cPLA2
      activation was accompanied by phosphorylation of its protein. These results
      indicate that cox-2 induction by IL-1alpha is not sufficient, but cPLA2
      activation by PDGF is crucial for IL-1alpha-induced PGE2 synthesis in mouse
      osteoblasts.

PMID- 9038216
TI  - Nitric oxide increases tumor necrosis factor production in differentiated U937
      cells by decreasing cyclic AMP.
AB  - Nitric oxide (NO) increases tumor necrosis factor (TNF) synthesis in human
      peripheral blood mononuclear cells by a cGMP-independent mechanism. NO has been
      shown to inhibit adenylate cyclase in cell membranes. Since cAMP down-regulates
      TNF transcription, we examined the possibility that NO enhances TNF synthesis by
      decreasing cAMP. U937 cells were induced to differentiate using phorbol myristate
      acetate (100 nM for 48 h) and then were incubated for 24 h with sodium
      nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP). These NO donors
      increased TNF production (7.0- and 15.6-fold, respectively, at 500 microM) in a
      dose-dependent manner (p = 0.002). However, SNP and SNAP did not elevate cGMP
      levels in U937 cell cultures, and the cGMP analog, 8-bromo-cGMP, had no effect on
      TNF production. In contrast, SNP (p = 0.001) and SNAP (p = 0.009) decreased
      intracellular cAMP levels by up to 51.5% over 24 h and, in the presence of a
      phosphodiesterase inhibitor, blunted isoproterenol-stimulated increases in cAMP
      by 21.8% (p = 0.004) and 27.6% (p = 0.008), respectively. H89, an inhibitor of
      cAMP-dependent protein kinase, dose dependently increased TNF production in
      phorbol myristate acetate-differentiated U937 cells in the absence (6.5-fold at
      30 microM; p = 0.035), but not in the presence (p = 0.77) of SNAP. Conversely,
      the cAMP analog dibutyryl cAMP (Bt2cAMP) blocked SNAP-induced TNF production (p =
      0.001). SNP and SNAP (500 microM) increased relative TNF mRNA levels by 57.5% (p
      = 0.045) and 66.2% (p = 0.001), respectively. This effect was prevented by
      Bt2cAMP. These results indicate that NO up-regulates TNF production by decreasing
      intracellular cAMP.

PMID- 9038217
TI  - Both SH2 domains are involved in interaction of SHP-1 with the epidermal growth
      factor receptor but cannot confer receptor-directed activity to SHP-1/SHP-2
      chimera.
AB  - The previously demonstrated functional and physical interaction of the SH2 domain
      protein-tyrosine phosphatase SHP-1 with the epidermal growth factor (EGF)
      receptor (Tomic, S., Greiser, U., Lammers, R., Kharitonenkov, A., Imyanitov, E.,
      Ullrich, A., and Bohmer, F. D. (1995) J. Biol. Chem. 270, 21277-21284) was
      investigated with respect to the involved structural elements of SHP-1. Various
      mutants of SHP-1 were transiently expressed in 293 or COS-7 cells and analyzed
      for their capacity to associate with immobilized autophosphorylated EGF receptor
      in vitro and to dephosphorylate coexpressed EGF receptor in intact cells.
      Inactivating point mutation of the C-terminal SH2 domain reduced the association
      weakly, point mutation of the N-terminal SH2 domain reduced association strongly
      and the respective double mutation abolished association totally. The capacity of
      SHP-1 to dephosphorylate coexpressed EGF receptor was impaired by all point
      mutations. Truncation of the N-terminal or of both SH2 domains strongly reduced
      or abolished association, respectively, but the truncated SHP-1 derivatives still
      dephosphorylated coexpressed EGF receptor effectively. Various chimeric protein
      tyrosine phosphatases constructed from SHP-1 and the closely homologous SHP-2
      dephosphorylated the EGF receptor when they contained the catalytic domain of SHP
      1. As native SHP-2, the chimera lacked activity toward the receptor when they
      contained the catalytic domain of SHP-2, despite their capacity to associate with
      the receptor and to dephosphorylate an artificial phosphopeptide. We conclude
      that the differential interaction of SHP-1 and SHP-2 with the EGF receptor is due
      to the specificity of the respective catalytic domains rather than to the
      specificity of the SH2 domains. Functional interaction of native SHP-1 with the
      EGF receptor requires association mediated by both SH2 domains.

PMID- 9038218
TI  - Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered
      phenotype, and resistance to cyclosporins.
AB  - A variant of the multidrug-resistant human sarcoma cell line Dx5 was derived by
      co-selection with doxorubicin and the cyclosporin D analogue PSC 833, a potent
      inhibitor of the multidrug transporter P-glycoprotein. The variant DxP cells
      manifest an altered phenotype compared with Dx5, with decreased cross-resistance
      to Vinca alkaloids and no resistance to dactinomycin. Resistance to doxorubicin
      and paclitaxel is retained. The multidrug resistance phenotype of DxP cells is
      not modulated by 2 microM PSC 833 or cyclosporine. DxP cells manifest a decreased
      ability to transport [3H]cyclosporine. DNA heteroduplex analysis and sequencing
      reveal a mutant mdr1 gene (deletion of a phenylalanine at amino acid residue 335)
      in the DxP cell line. The mutant P-glycoprotein has a decreased affinity for PSC
      833 and vinblastine and a decreased ability to transport rhodamine 123.
      Transfection of the mutant mdr1 gene into drug-sensitive MES-SA sarcoma cells
      confers resistance to both doxorubicin and PSC 833. Our study demonstrates that
      survival of cells exposed to doxorubicin and PSC 833 in a multistep selection
      occurred as a result of a P-glycoprotein mutation in transmembrane region 6.
      These data suggest that Phe335 is an important binding site on P-glycoprotein for
      substrates such as dactinomycin and vinblastine and for inhibitors such as
      cyclosporine and PSC 833.

PMID- 9038219
TI  - Signaling inositol polyphosphate-5-phosphatase. Characterization of activity and
      effect of GRB2 association.
AB  - An inositol polyphosphate-5-phosphatase (SIP-110) that binds the SH3 domains of
      the adaptor protein GRB2 was produced in Sf9 cells and characterized. SIP-110
      binds to GRB2 in vitro with a stoichiometry of 1 mol of GRB2/0.7 mol of SIP-110.
      GRB2 binding does not affect enzyme activity implying that GRB2 serves mainly to
      localize SIP-110 within cells. SIP-110 hydrolyses inositol (Ins)(1,3,4,5)P4 to
      Ins(1, 3,4)P3. The enzyme does not hydrolyze Ins(1,4,5)P3 that is a substrate for
      previously described 5-phosphatases nor does it hydrolyze phosphatidylinositol
      (PtdIns)(4,5)P2. SIP-110 also hydrolyzed PtdIns(3,4,5)P3 to PtdIns(3,4)P2 as did
      recombinant forms of two other 5-phosphatases designated as inositol
      polyphosphate-5- phosphatase II, and OCRL (the protein that is mutated in
      oculocerebrorenal syndrome). The inositol polyphosphate-5-phosphatase enzyme
      family now is represented by at least 9 distinct genes and includes enzymes that
      fall into 4 subfamilies based on their activities toward various 5-phosphatase
      substrates.

PMID- 9038220
TI  - Nuclease cleavage of the upstream half of the nontemplate strand DNA in an
      Escherichia coli transcription elongation complex causes upstream translocation
      and transcriptional arrest.
AB  - We tested the susceptibility of nucleic acid strands in a halted transcription
      elongation complex to digestion by micrococcal nuclease (MN). The 16-nucleotide
      nascent RNA was protected within RNA polymerase. A 27-28-nucleotide template
      strand DNA fragment also was resistant to MN digestion. However, the upstream
      half of the nontemplate DNA within this region was digested rapidly by MN,
      suggesting that the nontemplate strand emerges from the RNA polymerase near the
      middle of the melted transcription bubble with the bases oriented away from the
      enzyme surface. MN cleavage of the exposed nontemplate DNA shifted polymerase
      backward, making it unable to extend the RNA chain. However, the MN-trimmed G16
      complexes could be reactivated by GreB-stimulated cleavage of the nascent RNA.
      These results favor a model of transcriptional arrest involving upstream slippage
      of RNA polymerase along the RNA and DNA chains. They also suggest that the
      exposed segment of nontemplate DNA may directly or indirectly stabilize the
      lateral position of the transcription complex along the DNA.

PMID- 9038221
TI  - Characterization of two age-induced intracisternal A-particle-related transcripts
      in the mouse liver. Transcriptional read-through into an open reading frame with
      similarities to the yeast ccr4 transcription factor.
AB  - Intracisternal A-particle (IAP) sequences are endogenous retrovirus-like elements
      present at 1,000 copies in the mouse genome. We had previously identified IAP
      related transcripts of unusual size (6 and 10 kilobases (kb)), which are observed
      exclusively in the liver of the aging mouse. In this report, using cDNA libraries
      that we have constructed from the liver mRNAs of an aged DBA/2 mouse, we have
      cloned and entirely sequenced the corresponding cDNAs. Both are initiated within
      the 5' long terminal repeat of a type IDelta1 IAP sequence, and correspond to a
      read-through into a unique flanking cellular sequence containing a 966-nucleotide
      open reading frame, located 3' to the IAP sequence. The 6-kb IAP-related
      transcript corresponds to a post-transcriptional modification of the 10-kb mRNA,
      and is generated by a splicing event with the donor site in the IAP sequence, and
      the acceptor site 5' to the open reading frame. This open reading frame is
      located on chromosome 3, is evolutionarily conserved, and discloses significant
      similarity to the yeast CCR4 transcription factor at the amino acid level. The
      specific expression of these age-induced transcripts, which account for more than
      50% of the IAP-related transcripts in the liver of old mice, is therefore
      entirely consistent with the induction of a single genomic locus, thus
      strengthening the importance of position effects for the expression of
      transposable elements. Characterization of this locus should now allow studies on
      its chromatin and methylation status, and on the "molecular factors of
      senescence" possibly involved in its induction.

PMID- 9038222
TI  - Ribosome concentration contributes to discrimination against poly(A)- mRNA during
      translation initiation in Saccharomyces cerevisiae.
AB  - Inactivation of Saccharomyces cerevisiae poly(A) polymerase in a strain bearing
      the temperature-sensitive lethal pap1-1 mutation results in the synthesis of
      poly(A)- mRNAs that initiate translation with surprising efficiency. Translation
      of poly(A)- mRNAs after polyadenylation shut-off might result from an increase in
      the ratio of ribosomes and associated translation factors to mRNA, caused by the
      inability of poly(A)- mRNAs to accumulate to normal levels. To test this
      hypothesis, we used ribosomal subunit protein gene mutations to decrease either
      40 or 60 S ribosomal subunit concentrations in strains carrying the pap1-1
      mutation. Polyadenylation shut-off in such cells results in a nearly normal ratio
      of ribosomes to mRNA as revealed by polyribosome sedimentation analysis.
      Ribonuclease protection and Northern blot analyses showed that a significant
      percentage of poly(A)-deficient and poly(A)- mRNA associate with smaller
      polyribosomes compared with cells with normal ribosome levels. Analysis of the
      ratio of poly(A)-deficient and poly(A)- forms of a specific mRNA showed
      relatively more poly(A)- mRNA sedimenting with 20-60 S complexes than do poly(A)+
      forms, suggesting a block in an early step of the translation initiation of the
      poly(A)- transcripts. These findings support models featuring the poly(A) tail as
      an enhancer of translation and suggest that the full effect of a poly(A) tail on
      the initiation strength of a mRNA may require competition for a limited number of
      free ribosomes or translation factors.

PMID- 9038223
TI  - Thrombin receptors on human platelets. Initial localization and subsequent
      redistribution during platelet activation.
AB  - Platelet responses to thrombin are at least partly mediated by a G-protein
      coupled receptor whose NH2 terminus is a substrate for thrombin. In the present
      studies we have examined the location of thrombin receptors in resting platelets
      and followed their redistribution during platelet activation. The results reveal
      several new aspects of thrombin receptor biology. 1) On resting platelets,
      approximately two-thirds of the receptors were located in the plasma membrane.
      The remainder were present in the membranes of the surface connecting system. 2)
      When platelets were activated by ADP or a thromboxane analog, thrombin receptors
      that were initially in the surface connecting system were exposed on the platelet
      surface, increasing the number of detectable receptors by 40% and presumably
      making them available for subsequent activation by thrombin. 3) Platelet
      activation by thrombin rapidly abolished the binding of the antibodies whose
      epitopes are sensitive to receptor cleavage and left the platelets in a state
      refractory to both thrombin and the agonist peptide, SFLLRN. This was accompanied
      by a 60% decrease in the binding of receptor antibodies directed COOH-terminal to
      the cleavage site irrespective of whether the receptors were activated
      proteolytically by thrombin or nonproteolytically by SFLLRN. 4) The loss of
      antibody binding sites caused by thrombin was due in part to receptor
      internalization and in part to the shedding of thrombin receptors into membrane
      microparticles, especially under conditions in which aggregation was allowed to
      occur. However, at least 40% of the cleaved receptors remained on the platelet
      surface. 5) Lacking the ability to synthesize new receptors and lacking an
      intracellular reserve of preformed receptors comparable to that found in
      endothelial cells, platelets were unable to repopulate their surface with intact
      receptors following exposure to thrombin. This difference underlies the ability
      of endothelial cells to recover responsiveness to thrombin rapidly while
      platelets do not, despite the presence on both of the same receptor for thrombin.

PMID- 9038224
TI  - Ca2+ binding to troponin C in skinned skeletal muscle fibers assessed with caged
      Ca2+ and a Ca2+ fluorophore. Invariance of Ca2+ binding as a function of
      sarcomere length.
AB  - Ca2+ sensitivity of tension varies with sarcomere length in both skeletal and
      cardiac muscles. One possible explanation for this effect is that the Ca2+
      affinity of the regulatory protein troponin C decreases when sarcomere length is
      reduced. To examine length dependence of Ca2+ binding to troponin C in skeletal
      muscle, we developed a protocol to simultaneously monitor changes in sarcomere
      length, tension, and Ca2+ concentration following flash photolysis of caged Ca2+.
      In this protocol, [Ca2+] was rapidly increased by flash photolysis of caged Ca2+,
      and changes in [Ca2+] due to photolysis and the subsequent binding to troponin C
      were assessed using a Ca2+ fluorophore. Small bundles of fibers from rabbit
      skinned psoas muscles were loaded with Ca2+ fluorophore (Fluo-3) and caged Ca2+
      (dimethoxynitrophenamine or o-nitrophenyl-EGTA). The bundles were then
      transferred to silicone oil, where [Ca2+]free, tension, and sarcomere length were
      monitored before and after photolysis of caged Ca2+. Upon photolysis of caged
      Ca2+, fluorescence increased and then decayed to a new steady-state level within
      approximately 1 s, while tension increased to a new steady-state level within
      approximately 1.5 s. After extracting troponin C, fibers did not generate tension
      following the flash, but steady-state post-flash fluorescence was significantly
      greater than when troponin C was present. The difference in [Ca2+]free represents
      the amount of Ca2+ bound to troponin C. In fibers that were troponin C-replete,
      Ca2+ binding to troponin C did not differ at short (approximately 1.97 microm)
      and long (approximately 2.51 microm) sarcomere length, yet tension was
      approximately 50% greater at the long sarcomere length. These results show that
      the affinity of troponin C for Ca2+ is not altered by changes in sarcomere
      length, indicating that length-dependent changes in Ca2+ sensitivity of tension
      in skeletal muscle are not related to length-dependent changes in Ca2+ binding
      affinity of troponin C.

PMID- 9038225
TI  - The interorganellar interaction between distinct human mitochondria with deletion
      mutant mtDNA from a patient with mitochondrial disease and with HeLa mtDNA.
AB  - For the examination of possible intermitochondrial interaction of human
      mitochondria from different cells, cybrids were constructed by introducing HeLa
      mitochondria into cells with respiration-deficient (rho-) mitochondria.
      Respiration deficiency was due to the predominance of mutant mtDNA with a 5,196
      base pair deletion including five tRNA genes (DeltamtDNA5196). The HeLa mtDNA and
      DeltamtDNA5196 encoded chloramphenicol-resistant (CAPr) and chloramphenicol
      sensitive (CAPs) 16 S rRNA, respectively. The first evidence for the interaction
      was that polypeptides exclusively encoded by DeltamtDNA5196 were translated on
      the introduction of HeLa mitochondria, suggesting supplementation of the missing
      tRNAs by rho- mitochondria from HeLa mitochondria. Second, the exchange of
      mitochondrial rRNAs was observed; even in the presence of CAP, CAPs
      DeltamtDNA5196-specific polypeptides as well as those encoded by CAPr HeLa mtDNA
      were translated in the cybrids. These phenomena can be explained assuming that
      the translation in rho- mitochondria was restored by tRNAs and CAPr 16 S rRNA
      supplied from HeLa mitochondria, unambiguously indicating interorganellar
      interaction. These observations introduce a new concept of the dynamics of the
      mitochondrial genetic system and help in understanding the relationship among
      mtDNA mutations and expression of human mitochondrial diseases and aging.

PMID- 9038226
TI  - Gene expression of subunit c(P1), subunit c(P2), and oligomycin sensitivity
      conferring protein may play a key role in biogenesis of H+-ATP synthase in
      various rat tissues.
AB  - Mammalian H+-ATP synthase is a supramolecule composed of at least 14 subunits
      that have a constant stoichiometry. Nevertheless the coordinate regulation of the
      gene expressions of various subunits remains obscure. To clarify the coordinate
      transcriptional regulatory system of mammalian H+-ATP synthase, we determined the
      absolute amount of nine species of mRNAs for eight nuclear-encoded subunits of H+
      ATP synthase in different tissues of 8-week-old rats by use of the synthetic
      mRNAs and 32P-labeled DNA probes for each mRNA. Our quantitative analyses of the
      transcripts of H+-ATP synthase revealed that nine species of the subunits in
      different tissues of 8-week-old rats were divisible into two groups: a high
      transcript gene (HTG) group (beta-subunit, subunit b, subunit d, subunit e, and
      Factor 6) and a low transcript gene (LTG) group (subunit c(P1), subunit c(P2),
      IF1, and oligomycin sensitivity-conferring protein). The transcription step of
      LTG could constitute a bottleneck in the biogenesis of H+-ATP synthase. Thus, the
      transcriptional regulatory system of the LTG may play a key role in the
      biogenesis of mammalian H+-ATP synthase. The HTG were transcribed in a tissue
      specific manner that corresponds with energy demand in the tissues. However,
      there was no tissue specificity in subunit c(P2). Furthermore, the tissue
      specificity of the transcript of IF1 differed substantially from that of HTG,
      suggesting that it could be crucial in the protection of mitochondrial membrane
      under abnormal conditions.

PMID- 9038227
TI  - Nerve growth factor decreases soluble guanylate cyclase in rat pheochromocytoma
      PC12 cells.
AB  - Nitric oxide (NO) modulates neurotransmission in the central and peripheral
      nervous systems. NO acts, in part, by stimulating cGMP production by soluble
      guanylate cyclase (sGC), an obligate heterodimer composed of alpha and beta
      subunits. To investigate mechanisms that regulate responsiveness to NO in the
      nervous system, sGC regulation was examined in a rat pheochromocytoma cell line
      (PC12) exposed to nerve growth factor (NGF). NGF decreased sGC alpha1 and beta1
      subunit mRNA and protein levels as well as NO-stimulated sGC enzyme activity. The
      NGF-mediated decrease in sGC subunit mRNA levels was blocked by 5'-deoxy-5'
      methylthioadenosine (an inhibitor of NGF-induced tyrosine phosphorylation). NGF
      did not decrease sGC subunit mRNA levels in PC12 cells containing a mutant Ras
      protein that blocks Ras-dependent intracellular signaling. Incubation of PC12
      cells with a transcription inhibitor (actinomycin D) or protein synthesis
      inhibitors (anisomycin or cycloheximide) attenuated the ability of NGF to
      decrease sGC subunit mRNA levels. Moreover, sGC subunit mRNA levels decreased
      more rapidly in NGF-treated cells than in actinomycin D-treated cells, suggesting
      that NGF decreases sGC subunit mRNA stability. Thus, NGF decreases sGC subunit
      mRNA levels via mechanisms that are dependent on protein tyrosine phosphorylation
      and Ras activation. The effect of NGF on sGC subunit mRNA stability appears to be
      transcription- and translation-dependent. Modulation of sGC subunit levels and
      enzyme activity in PC12 cells suggests that NO responsiveness may be regulated in
      the nervous system by NGF.

PMID- 9038228
TI  - Relationship between the peptide-sensitive channel and the mitochondrial outer
      membrane protein translocation machinery.
AB  - The peptide-sensitive channel (PSC), a cationic channel of the mitochondrial
      outer membrane, is blocked by synthetic mitochondrial presequences and by
      nonmitochondrial basic peptides such as dynorphin B(1-13). Both types of peptides
      are imported into mitochondria. However, the import of dynorphin B(1-13) had to
      be further characterized since its properties differed from those of the general
      import pathway used by mitochondrial peptides. Cross-linking experiments with
      iodinated dynorphin B(1-13) led to the labeling of TOM 40/ISP 42, a component of
      the protein import machinery of the outer membrane. Accordingly, dynorphin B(1
      13) could also be used as a presequence to direct the import of a cytosolic
      protein into the mitochondria. Pretreatment of intact mitochondria by trypsin
      removed components capable of discriminating between true mitochondrial
      presequences and other basic peptides active on the PSC. After proteolysis, both
      types of peptides appeared to cross the outer membrane through the same pathway.
      Involvement of the PSC in the translocation complex was shown by
      immunoprecipitation of the PSC activity by anti-ISP 42 antibodies. Taken
      together, the present data reinforce the hypothesis that the PSC is the pore
      responsible for the translocation of protein through the outer membrane.

PMID- 9038229
TI  - Tyrosine hydroxylase gene promoter activity is regulated by both cyclic AMP
      responsive element and AP1 sites following calcium influx. Evidence for cyclic
      amp-responsive element binding protein-independent regulation.
AB  - Membrane depolarization of PC12 cells using 50 mM KCl leads to induction of
      tyrosine hydroxylase (TH) mRNA. This induction of TH mRNA is apparently due to
      increased TH gene promoter activity mediated by the influx of Ca2+. In PC12 cells
      transiently transfected with a chimeric gene expressing chloramphenicol
      acetyltransferase (CAT) driven by the proximal TH gene 5'-flanking region, 50 mM
      KCl increases TH gene promoter activity 3-4-fold. Promoter analysis utilizing TH
      CAT constructs containing mutagenized sequences indicates that this response to
      the depolarization-mediated influx of Ca2+ is primarily dependent on both the TH
      cAMP-responsive element (CRE) and TH activating protein-1 (AP1) site. Minimal
      promoter constructs that contain a single copy of either the TH CRE or TH AP1
      site fused upstream of the TH gene basal promoter are only modestly responsive or
      nonresponsive, respectively, to depolarization. However, both these constructs
      are strongly responsive to the calcium ionophore, A23187. Gel shift assays
      indicate that TH AP1 complex formation is dramatically increased after treatment
      with either 50 mM KCl or A23187. Using antibodies to transcription factors of the
      Fos and Jun families, we show that the nuclear proteins comprising the inducible
      TH AP1 complex include c-Fos, c-Jun, JunB, and JunD. In cAMP-responsive element
      binding protein (CREB)-deficient cell lines that express antisense RNA
      complementary to CREB mRNA, the response of the TH gene promoter to cyclic AMP is
      dramatically inhibited, but the response to A23187 remains robust. This result
      indicates that transcription factors other than CREB can participate in the Ca2+
      mediated regulation of the TH gene. In summary, our results support the
      hypothesis that regulation of the TH gene by Ca2+ is mediated by mechanisms
      involving both the TH CRE and TH AP1 sites and that transcription factors other
      than or in addition to CREB participate in this response.

PMID- 9038230
TI  - Activation of human matrix metalloproteinases by various bacterial proteinases.
AB  - Matrix metalloproteinases (MMPs) are zinc-containing proteinases that participate
      in tissue remodeling under physiological and pathological conditions. To test the
      involvement of bacterial proteinases in tissue injury during bacterial
      infections, we investigated the activation potential of various bacterial
      proteinases against precursors of MMPs (proMMPs) purified from human neutrophils
      (proMMP-8 and -9) and from human fibrosarcoma cells (proMMP-1). Each proMMP was
      subjected to treatment with a series of bacterial proteinases at molar ratios of
      0.01-0.1 (bacterial proteinase to proMMP), and activities of MMPs generated were
      determined. Among six different bacterial proteinases, thermolysin family enzymes
      (family M4) such as Pseudomonas aeruginosa elastase, Vibrio cholerae proteinase,
      and thermolysin strongly activated all three proMMPs via limited proteolysis to
      generate active forms of the MMPs. N-terminal sequence analysis of the active
      MMPs revealed that cleavage occurred at the Val82-Leu83 and Thr90-Phe91 bonds of
      proMMP-1 and proMMP-9, respectively, which are located near the N terminus of the
      catalytic domain of MMPs. In contrast, Serratia 56-kDa proteinase and Pseudomonas
      alkaline proteinase, both of which are classified as members of the serralysin
      subfamily of zinc metalloproteinases (family M10), and Serratia 73-kDa thiol
      proteinase did not evidence proteolytic processing or activation of proMMP-1, -8,
      and -9 under these experimental conditions. These results indicate that bacterial
      proteinases may play an important role in tissue destruction and disintegration
      of extracellular matrix at the site of infections.

PMID- 9038231
TI  - Staphylokinase requires NH2-terminal proteolysis for plasminogen activation.
AB  - Staphylokinase (Sak), a single-chain protein comprising 136 amino acids with NH2
      terminal sequence,SSSFDKGKYKKGDDA forms a complex with plasmin, that is endowed
      with plasminogen activating properties. Plasmin is presumed to process mature
      (high molecular weight, HMW) Sak to low molecular weight derivatives (LMW-Sak),
      primarily by hydrolyzing the Lys10-Lys11 peptide bond, but the kinetics of
      plasminogen activation by HMW-Sak and LMW-Sak are very similar. Here, the
      requirement of NH2-terminal proteolysis of Sak for the induction of plasminogen
      activating potential was studied by mutagenesis of Lys10 and Lys11 in combination
      with NH2-terminal microsequence analysis of equimolar mixtures of Sak and
      plasminogen and determination of kinetic parameters of plasminogen activation by
      catalytic amounts of Sak. Substitution of Lys10 with Arg did not affect
      processing of the Arg10-Lys11 site nor plasminogen activation, whereas
      substitution with His resulted in cleavage of the Lys11-Gly12 peptide bond and
      abolished plasminogen activation. Substitution of Lys11 with Arg did not affect
      Lys10-Arg11 processing or plasminogen activation, whereas replacement with His
      did not prevent Lys10-His11 hydrolysis but abolished plasminogen activation.
      Substitution of Lys11 with Cys yielded an inactive processed derivative which was
      fully activated by aminoethylation. Deletion of the 10 NH2-terminal amino acids
      did not affect plasminogen activation, but additional deletion of Lys11
      eliminated plasminogen activation. Thus generation of plasminogen activator
      potential in Sak proceeds via plasmin-mediated removal of the 10 NH2-terminal
      amino acids with exposure of Lys11 as the new NH2 terminus. This provides a
      structural basis for the hypothesis, derived from kinetic measurements, that
      plasminogen activation by Sak needs to be primed by plasmin and a mechanism for
      the high fibrin selectivity of Sak in a plasma milieu.

PMID- 9038232
TI  - Differential associations between the cytoplasmic regions of the interleukin-12
      receptor subunits beta1 and beta2 and JAK kinases.
AB  - The role of the cytoplasmic regions of interleukin-12 receptors (IL-12R) beta1
      and beta2 in stimulating proliferation was examined. The transmembrane and
      cytoplasmic regions of IL-12Rbeta1 or IL-12Rbeta2 were fused to the extracellular
      domain of the epidermal growth factor (EGF) receptor, yielding chimeric receptors
      E12R1 and E12R2, respectively. These chimeras were stably transfected into BaF3
      cells, a factor-dependent murine pro-B cell line. Only E12R2 or E12R1+E12R2
      transfectants were capable of EGF-dependent proliferation. EGF-dependent
      phosphorylation of E12R2, JAK2, Tyk2, and STAT3 was observed. JAK2 was
      phosphorylated in E12R1-, E12R2-, and E12R1+E12R2-expressing cells. However,
      direct associations were detectable only between E12R2 and JAK2. Tyk2
      phosphorylation was observed only in cells expressing E12R1 or E12R1+E12R2. In
      parallel with this activation pattern, direct interactions only between Tyk2 and
      E12R1 were demonstrable. Phosphorylation of STAT3 was observed in cells
      expressing E12R1, E12R2, and E12R1+E12R2. The expression levels of STAT4 protein
      in BaF3 cells are undetectable by the methods employed here; therefore, STAT4
      phosphorylation was not observed. Taken together, the data indicate that
      differential interactions take place between the cytoplasmic regions of the two
      IL-12R subunits and JAK2/Tyk2 and that the cytoplasmic region of IL-12Rbeta2
      alone is capable of delivering a proliferative signal.

PMID- 9038233
TI  - Identification and characterization of galectin-9, a novel beta-galactoside
      binding mammalian lectin.
AB  - A 36-kDa beta-galactoside mammalian lectin protein, designated as galectin-9, was
      isolated from mouse embryonic kidney by using a degenerate primer polymerase
      chain reaction and cloning strategy. Its deduced amino acid sequence had the
      characteristic conserved sequence motif of galectins. Endogenous galectin-9,
      extracted from liver and thymus, as well as recombinant galectin-9 exhibited
      specific binding activity for the lactosyl group. It had two distinct N- and C
      terminal carbohydrate-binding domains connected by a link peptide, with no
      homology to any other protein. Galectin-9 had an alternate splicing isoform,
      exclusively expressed in the small intestine with a 31-amino acid insertion
      between the N-terminal domain and link peptide. Sequence homology analysis
      revealed that the C-terminal carbohydrate-binding domain of mouse galectin-9 had
      extensive similarity to that of monomeric rat galectin-5. The presence of
      galectin-5 in the mouse could not be demonstrated by polymerase chain reaction or
      by Northern or Southern blot genomic DNA analyses. Sequence comparison of rat
      galectin-5 and rat galectin-9 cDNA did not reveal identical nucleotide sequences
      in the overlapping C-terminal carbohydrate-binding domain, indicating that
      galectin-9 is not an alternative splicing isoform of galectin-5. However,
      galectin-9 had a sequence identical with that of its intestinal isoform in the
      overlapping regions in both species. Southern blot genomic DNA analyses, using
      the galectin-9 specific probe derived from the N-terminal carbohydrate-binding
      domain, indicated the presence of a novel gene encoding galectin-9 in both mice
      and rats. In contrast to galectin-5, which is mainly expressed in erythrocytes,
      galectin-9 was found to be widely distributed, i.e. in liver, small intestine,
      thymus > kidney, spleen, lung, cardiac and skeletal muscle > reticulocyte, brain.
      Collectively, these data indicate that galectin-9 is a new member of the galectin
      gene family and has a unique intestinal isoform.

PMID- 9038234
TI  - Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin
      treatment fail to generate a calcium-mediated grp78/grp94 stress response.
AB  - grp78/grp94 induction is critical for maintaining the viability of epithelial
      cells and fibroblasts following treatment with thapsigargin (TG), an inhibitor of
      Ca2+ uptake into the endoplasmic reticulum. In contrast to these cell types,
      WEHI7.2 mouse lymphoma cells undergo apoptosis when treated with TG, prompting us
      to examine the grp78/grp94 stress response in WEHI7.2 cells. TG treatment failed
      to induce grp78/grp94 transcription in WEHI7.2 cells, measured by Northern
      hybridization and nuclear run-on assays, even if the cells were protected from
      apoptosis by overexpressing bcl-2. However, grp78/grp94 transcription was induced
      by the glycosylation inhibitor tunicamycin, suggesting that there are at least
      two grp78/grp94 signaling pathways, one in response to TG-induced endoplasmic
      reticulum Ca2+ pool depletion, which is inoperable in WEHI7.2 cells, and one in
      response to glycosylation inhibition, which is operable in WEHI7.2 cells. Studies
      of additional lymphoid lines, as well as several nonlymphoid lines, suggested a
      correlation between grp78/grp94 induction and resistance to apoptosis following
      TG treatment. In conclusion, the vulnerability of TG-treated WEHI7.2 cells to
      apoptosis may be due to failure to signal a grp78/grp94 stress response.

PMID- 9038235
TI  - The IPCS collaborative study on neurobehavioral screening methods.
AB  - The International Programme on Chemical Safety sponsored a collaborative study to
      evaluate the utility of neurobehavioral test methods for identifying neurotoxic
      chemicals. The protocol consisted of a functional observational battery and
      automated assessment of motor activity. The study involved four laboratories in
      the United States and four in Europe, each of which evaluated the dose- and time
      related effects of seven prototypic chemicals following both single and 4-week
      repeated exposures. The protocol was designed to assess the general utility and
      reliability of neurobehavioral screening procedures in a diversity of testing
      situations. The results of chemical testing indicated that all participating
      laboratories generally could detect and characterize the effects of known
      neurotoxicants, despite some differences on specific endpoints. These data
      provide important information regarding the reliability and sensitivity of
      neurobehavioral screening methods over a range of laboratory conditions. The
      purpose of this workshop was to describe the background and study design of the
      collaborative effort, present the data (including comparison of results across
      laboratories), and discuss issues regarding the conduct and interpretation of
      these behavioral tests, as well as future directions for neurotoxicity screening.

PMID- 9038236
TI  - Subchronic inhalation studies of styrene in CD rats and CD-1 mice.
AB  - Groups of 10 male and 10 female Charles River (CRL) CD (Sprague-Dawley-derived)
      rats were exposed to styrene vapor at 0, 200, 500, 1000, or 1500 ppm 6 hr per day
      5 days per week for 13 weeks. Styrene had no effect on survival, hematology, or
      clinical chemistry. Males at 1500 ppm weighed 10% less after 13 weeks and males
      and females at 1000 and 1500 ppm consumed more water than controls.
      Histopathologic changes were confined to the olfactory epithelium of the nasal
      mucosa. Groups of 20 male and 20 female CRL CD-1 and B6C3F1 mice were exposed to
      styrene vapor at 0, 15, 60, 250, or 500 ppm 6 hr per day 5 days per week for 2
      weeks. Mortality was observed in both CD-1 and B6C3F1 mice exposed to 250 or 500
      ppm; more female mice, but not males, died from exposure to 250 ppm than from 500
      ppm. Groups of 10 male and 10 female CRL CD-1 mice were exposed to styrene vapors
      at 0, 50, 100, 150, or 200 ppm 6 hr per day 5 days per week for 13 weeks. Two
      females exposed to 200 ppm died during the first week. Liver toxicity was evident
      in the decedents and in some female survivors at 200 ppm. Changes were observed
      in the lungs of mice exposed to 100, 150, or 200 ppm and in the nasal passages of
      all treatment groups, those exposed to 50 ppm being less affected. Satellite
      groups of 15 male rats and 30 male mice were exposed as described above for 2, 5,
      or 13 weeks for measurement of cell proliferation (BrdU labeling). No increase in
      cell proliferation was found in liver of rats or mice or in cells of the
      bronchiolar or alveolar region of the lung of rats. No increase in labeling index
      of type II pneumocytes was seen in mouse lungs, while at 150 and 200 ppm, an
      increased labeling index of Clara cells was seen after 2 weeks and in occasional
      mice after 5 weeks. Large variations in the labeling index among animals
      emphasize the need for large group sizes. For nasal tract effects, a NOAEL was
      not found in CD-1 mice, but in CD rats, the NOAEL was 200 ppm. For other effects,
      the NOAEL was 500 ppm in rats and 50 ppm in mice.

PMID- 9038237
TI  - Systemic and developmental toxicity of dermally applied syntower bottoms in rats.
AB  - Syntower bottoms (STB) was evaluated for subchronic and developmental toxicity.
      In the subchronic study, undiluted STB was applied on the shaved backs of male
      and female rats at dose levels of 0, 8, 30, 125, and 500 mg/kg for 13 weeks, 5
      days per week. Exposure sites were not covered. In the developmental toxicity
      study, STB was similarly applied, but to pregnant rats at dose levels of 0, 8,
      30, and 125 mg/kg on Gestation Days 0-19. In addition, 4 mg/kg was dosed as 8
      mg/kg every other day, starting on Gestation Day 0, and 500 mg/kg was dosed on
      Gestation Days 10-12. Evidence of toxicity observed in the subchronic study
      included death, decreased body weights, aberrant serum chemistry and hematology
      values, altered organ weights, and histopathologic changes in a variety of
      organs. A no observed adverse effect level for systemic toxicity could not be
      established. Evidence of maternal toxicity was observed at all exposure levels in
      the development study. Regardless of the length of the exposure period, STB was
      toxic to the developing conceptus. Evidence of developmental toxicity observed
      included increased resorptions with a concomitant decrease in litter size and
      reduced fetal body weights. Cleft palate was observed in fetuses exposed in utero
      to STB during Gestation Days 10-12 at 500 mg/kg. No evidence of teratogenicity
      was observed when the exposure period was throughout gestation. Ossification
      delays were observed in fetuses exposed in utero to STB at doses in excess of 4
      mg/kg. A no observed adverse effect level for maternal and developmental toxicity
      could not be established.

PMID- 9038238
TI  - The in vivo effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate on
      N-methyl-N-nitrosourea-induced apoptosis in mouse hair follicles.
AB  - This study assessed the in vivo relationship between apoptosis induced by the
      tumor initiator N-methyl-N-nitrosourea (MNU) and action of the tumor promoter 12
      O-tetradecanoylphorbol-13-acetate (TPA) in mouse hair follicle matrix cells.
      Mouse hair follicles were stimulated to grow hair synchronously by plucking
      resting hairs and MNU was applied to the plucked skin as the apoptosis inducer.
      The effects of TPA on MNU-induced apoptosis, when given at different intervals
      before or after MNU treatment, were examined. Changes in the percentage of
      apoptotic cells among total hair matrix cells after TPA treatment were measured.
      A significant suppression in levels of MNU-induced apoptosis was observed in the
      animals receiving TPA 1 to 6 hr following the induction. Administration of TPA
      before MNU caused a reduction in numbers of apoptotic cells over the control
      groups, but the differences were not significant. Determination of the diurnal
      variation in apoptotic levels in vehicle-treated mouse hair follicles revealed a
      relatively constant baseline pattern, suggesting that the above apoptotic
      responses to MNU and TPA were not affected by the background levels of apoptosis.
      The findings provided in vivo evidence which would support the hypothesis that
      TPA promotes tumorigenesis by preventing carcinogen-initiated cells from
      undergoing apoptotic death.

PMID- 9038239
TI  - Effects of intranasal exposure to spores of Stachybotrys atra in mice.
AB  - The effects of highly toxic and nontoxic spores of Stachybotrys atra were
      investigated in mice after six intranasal administrations of 1 x 10(5) and 1 x
      10(3) spores in phosphate-buffered saline during a 3-week period. Toxic spores
      contained the trichothecene mycotoxins, satratoxins G and H, as well as the
      immunosuppressant stachybotrylactones and -lactams. No trichothecenes were
      detected in the nontoxic spores, and they contained only minor amounts of
      stachybotrylactones and -lactams. In mice injected with toxic and nontoxic
      spores, the platelet count was decreased and leucocyte and erythrocyte counts,
      hemoglobin concentration, and hematocrit were increased. No IgG antibodies to S.
      atra were detected in sera of mice exposed intranasally to spores. No
      histological changes were detected in spleen, thymus, or intestines of mice. The
      mice receiving 1 x 10(5) toxic spores intranasally developed severe inflammatory
      changes within both bronchioles and alveoli. Hemorrhage was detected in alveoli.
      The mice receiving 1 x 10(5) nontoxic spores also developed inflammatory changes
      in the lungs, but these changes were significantly milder than those in mice
      receiving toxic spores. The mice receiving 1 x 10(3) toxic spores developed
      inflammatory changes in the lungs that were less severe than those in the mice
      receiving 1 x 10(5) toxic spores. No inflammatory changes were detected in the
      mice receiving 1 x 10(3) of nontoxic spores. The present findings indicate that
      exposure to S. atra spores containing toxins (satratoxins) can be a significant
      health risk.

PMID- 9038241
TI  - Activation of CGS 12094 (prinomide metabolite) to 1,4-benzoquinone by
      myeloperoxidase: implications for human idiosyncratic agranulocytosis.
AB  - Many marketed pharmaceuticals are known to cause idiosyncratic agranulocytosis in
      humans. Similarly prinomide, an antiinflammatory drug, was associated with a low
      incidence of agranulocytosis (<0.3%) in clinical trials, even though chronic
      toxicity studies in rodents and primates showed no evidence of agranulocytosis
      with either prinomide or its parahydroxy metabolite, CGS 12094. To investigate
      mechanisms for this human specific toxicity, experiments were conducted to study
      the metabolism of prinomide and CGS 12094 by myeloperoxidase (MPO), a major
      enzyme of neutrophils and leukocyte progenitor cells. Although prinomide was not
      metabolized by human MPO, CGS 12094 was rapidly metabolized (>90%; 2 min); this
      reaction was dependent on H2O2 and MPO and was inhibited by azide. During the MPO
      catalyzed metabolism of CGS 12094, reactive intermediates that irreversibly bound
      to protein and cysteine were generated. One of the reactive metabolites generated
      was identified by mass spectroscopy and trapping with cysteine as 1,4
      benzoquinone, a compound implicated in the myelotoxicity associated with benzene.
      Thus during conditions which lead to elevated levels of H2O2 (e.g., active
      inflammation), CGS 12094 is rapidly metabolized by MPO to reactive intermediates
      that may be related to prinomide-induced agranulocytosis.

PMID- 9038240
TI  - A comparison of the acute behavioral effects of inhaled amyl, ethyl, and butyl
      acetate in mice.
AB  - The acute neurobehavioral effects of three acetates (amyl, ethyl, and n-butyl
      acetate) were investigated after 20-min inhalation exposures in mice using
      locomotor activity and a functional observational battery (FOB). Ethyl and n
      butyl acetate produced significant decreases in locomotor activity at the highest
      concentrations examined, while amyl acetate was without effect. Minimally
      effective concentrations for activity-decreasing effects were 2000 ppm for ethyl
      acetate and 8000 ppm for n-butyl acetate. The potency order was similar in the
      FOB where ethyl acetate was more potent in disrupting the neurobehavioral
      measures. The FOB profile of effects for all three acetates included changes in
      posture, decreased arousal, increased tonic/clonic movements, disturbances in
      gait, delayed righting reflexes, and increased sensorimotor reactivity.
      Furthermore, handling-induced convulsions were produced in some mice acutely
      exposed to each of these acetates. Recovery from the acute effects of these
      acetates was rapid and began within minutes of removal from the exposure chamber.
      The acetates produced a profile of neurobehavioral effects that were different
      from those reported for depressant solvents (i.e., toluene, 1,1,1
      trichloroethane) that are subject to abuse. Evidence is emerging for qualitative
      differences in the acute neurobehavioral effects of various volatile chemicals.

PMID- 9038242
TI  - The effects of dietary boron on bone strength in rats.
AB  - Previous studies from our laboratory found that when boric acid (BA) was
      administered in the diet to rats, boron levels in bone were approximately
      fourfold greater than serum levels. The current studies were undertaken to
      determine if these elevations produced adverse effects on several bone-related
      measures, including serum electrolyte levels, bone structure, and bone strength.
      Data from two studies are presented: in the first study, young adult male rats
      consumed a powdered diet containing 0, 3000, 4500, 6000, or 9000 ppm BA for 9
      weeks. Endpoints were serum calcium, phosphorous, potassium, and chloride, as
      well as blood and bone boron concentrations ([B]) measured weekly during the 9
      week exposure period, and at 8, 16, 24, and 32 weeks after the end of exposure.
      In the second study, the male and female young adult rats diet contained 0, 200,
      1000, 3000, or 9000 ppm BA for 12 weeks; endpoints measured weekly were serum
      levels of calcium, phosphorous, and magnesium, bone [B], and bone structure
      (humerus) and strength (tibia, femur, and lumbar vertebrae). In treated rats,
      calcium was reduced in the first study but not the second. Serum phosphorous was
      reduced in both studies; potassium was unchanged, chloride was increased by 1%,
      and magnesium was reduced in all BA-exposed groups in the second study, to a
      maximal 19% reduction. Bone [B] was consistently increased in all treated groups,
      to concentrations approximately fourfold those of serum. After cessation of
      exposure, serum and urinary boron concentrations dropped to within control values
      within a week. However, even 32 weeks after the end of exposure, bone [B]
      remained threefold greater than controls. Male tibia and femur resistance to
      bending was unchanged. However, vertebral strength in compression was
      significantly increased by 5-10% in all dose groups (200 to 9000 ppm). The
      pattern was substantially similar in females. Only the humerus was examined by
      light microscopy and was found to be unchanged at any level of BA consumption.
      These data show that, despite a reduction in some serum electrolyte levels, BA
      consumption increased vertebral resistance to crush force, without detectably
      altering the microscopic structure of the humerus or the resistance of femur and
      tibia to a bending load. This increase in compression resistance occurred at
      exposure levels substantially below those that were previously reported to be
      reproductively toxic.

PMID- 9038243
TI  - Comparative studies of chromaffin cell proliferation in the adrenal medulla of
      rats and mice.
AB  - Spontaneous and drug-induced pheochromocytomas are common in rats and rare in
      mice. The antihypertensive drug reserpine has been shown to both induce
      pheochromocytomas and stimulate chromaffin cell proliferation in rats, leading to
      the hypothesis that reserpine causes pheochromocytomas indirectly by providing a
      proliferative setting in which DNA damage may occur. The present investigation
      was undertaken to obtain baseline information on the relationship across species
      between chromaffin cell proliferation and pheochromocytomas. Basal chromaffin
      cell proliferation was compared in age-matched young adult mice and rats. In
      addition, mice were studied for adrenal medullary responses to reserpine, and
      mouse chromaffin cells in vitro were studied for responses to agents that are
      mitogenic for cultured rat chromaffin cells. Concurrently maintained F-344 rats
      and several strains of mice showed no significant difference in basal BrdU
      incorporation over a 1-week period. Mice also showed an adrenal medullary
      proliferative response to reserpine that was comparable to the response
      previously reported for rats. However, there was a marked disparity between rat
      and mouse chromaffin cells in vitro, and cultured mouse chromaffin cells did not
      respond to any mitogens. The in vivo data indicate that interspecies differences
      in basal- or reserpine-stimulated chromaffin cell proliferation sufficient to
      account for different frequencies of pheochromocytomas are not detectable at a
      single time point in young adult animals. However, the possibility that such
      differences might emerge with aging has not been ruled out. These data further
      suggest either that stimulation of chromaffin cell proliferation might be
      necessary but not sufficient for development of pheochromocytomas or that
      stimulated proliferation in mice might not be sustained. The inability of
      cultured mouse chromaffin cells to respond to mitogens raises the speculation of
      whether mechanisms that prevent proliferation of normal chromaffin cells in vitro
      might also help to protect mice from developing pheochromocytomas.

PMID- 9038244
TI  - The abstraction of intervening concepts from experience with multiple input
      multiple output causal environments.
AB  - The purpose of this article is threefold: (a) introduce a new paradigm for
      investigating how intervening concepts are learned, (b) report four new
      experiments that provide converging evidence for the acquisition of intervening
      concepts, and (c) propose a simple associative learning mechanism to account for
      the results. The new paradigm utilizes a stimulus-response-feedback task in which
      subjects learn trial by trial how a multivariate set of inputs maps into a
      multivariate set of outputs. The first two experiments use evidence based on a
      principal component analysis to replicate the finding that intervening-concept
      learning occurs spontaneously, but only in environments that contain an
      intervening factor. The next experiment provides a second converging line of
      evidence for this conclusion by showing that subjects can use an intervening
      concept to make accurate inferences to a new fourth output during a transfer
      test. The last experiment provides a third line of evidence by showing that
      subjects can use an intervening concept to make accurate inferences from a new
      fourth input. The results are explained by a hidden-unit connectionist learning
      mechanism that includes both accuracy and parsimony as learning objectives.

PMID- 9038245
TI  - Categorization and reasoning among tree experts: do all roads lead to Rome?
AB  - To what degree do conceptual systems reflect universal patterns of featural
      covariation in the world (similarity) or universal organizing principles of mind,
      and to what degree do they reflect specific goals, theories, and beliefs of the
      categorizer? This question was addressed in experiments concerned with
      categorization and reasoning among different types of tree experts (e.g.,
      taxonomists, landscape workers, parks maintenance personnel). The results show an
      intriguing pattern of similarities and differences. Differences in sorting
      between taxonomists and maintenance workers reflect differences in weighting of
      morphological features. Landscape workers, in contrast, sort trees into goal
      derived categories based on utilitarian concerns. These sorting patterns carry
      over into category-based reasoning for the taxonomists and maintenance personnel
      but not the landscape workers. These generalizations interact with taxonomic rank
      and suggest that the genus (or folk generic) level is relatively and in some
      cases absolutely privileged. Implications of these findings for theories of
      categorization are discussed.

PMID- 9038246
TI  - Natural and photoperiodically induced changes in plasma prolactin levels in male
      great tits.
AB  - Plasma levels of prolactin showed a pronounced annual cycle in free-living male
      great tits (Parus major). During the period from August to April, levels were
      very low. Prolactin levels started to increase in mid-April, and maximal levels
      were reached in June. By mid-July prolactin levels had decreased to near basal
      levels. The exact breeding stage was known for all males captured during the
      breeding period, and prolactin levels increased continuously from the period of
      territorial defense to the nestling period. Males were exposed to different light
      regimes at three different times of the year (late August, late November, and
      early March). Males exposed to 14L:10D (14 h light:10 h darkness) and 20L:4D
      showed pronounced prolactin cycles at all times of the year, but the patterns
      differed markedly with the season. In November the 20L:4D and the 14L:10D
      prolactin patterns differed markedly from each other. In the 20L:4D group
      prolactin levels started to increase before testes had reached maximal size,
      whereas in the 14L:10D group prolactin levels did not start to increase until
      testes were almost completely regressed. In early March the prolactin pattern of
      change over time was the same for great tits kept on 20L:4D and 14L:10D. In both
      cases prolactin levels increased during the testicular growth period, and
      prolactin levels were maximal during the period of spermatogenesis. Prolactin
      levels did not change over time in males kept on 8L:16D in August and November.
      Males exposed to short days in early March showed a significant increase in
      prolactin levels about 3 weeks after the onset of the experiment. Plasma levels
      of prolactin in males castrated in late November and exposed to a 20L:4D light
      regime did not differ from those in intact males. In castrated males given a
      testosterone implant prolactin levels immediately increased to significantly
      higher levels than those observed in intact or castrated males. Prolactin levels
      remained significantly higher in the testosterone implanted males for about a
      month. In one group of castrated birds the testosterone implant was removed 13
      days after the onset of the experiment. This removal resulted in a significant
      decrease in circulating levels of prolactin.

PMID- 9038248
TI  - Binding activity of 5alpha-reduced gestagens to the progestin receptor from
      African elephant (Loxodonta africana).
AB  - Recent findings in the African elephant (Loxodonta africana) indicate that the
      major progestins contained within and biosynthesized by corpora lutea are 5alpha
      reduced metabolites and that progesterone is quantitatively of minor importance.
      The specific gestagenic action within the reproductive tract of elephants was
      determined by measurement of relative binding affinity of the respective
      progestins to the gestagen receptor extracted from elephant endometrium. The
      cytosol was incubated with 40 nmol/liter [3H]ORG-2058 and increasing
      concentrations of the tested progestin. Progesterone (P4), 5alpha-pregnane-3,20
      dione (DHP), and 5alpha-pregnane-3alpha-ol-20-one (5alpha-P-3OH) were used. The
      competition for binding sites on the progestin receptor was shown by decreasing
      counts measured after extraction with scintillation fluid. The progestin
      concentration which induced a 50% reduction of measured counts was estimated
      (C50) and relative binding affinity of progesterone to other progestins was
      calculated (RBA = C50progestin/C50p4). The relative binding affinity of DHP to P4
      at the gestagen receptor of elephant endometrium was equivalent. The other 5alpha
      reduced progestin (5alpha-P-3OH) showed no competition to the [3H]ORG-2058
      receptor binding. We conclude that the biological significance of P4 and DHP at
      the receptor level is very similar. The higher quantitative levels of DHP in
      corpus luteum and serum support the hypothesis that this progestin is the major
      gestagen in the elephants, whereas 5alpha-P-3OH is an inactive metabolite.

PMID- 9038247
TI  - Relaxin: an ovarian hormone in an avian species (Gallus domesticus).
AB  - The objective of this study was to characterize the biochemical, immunological,
      and biological activity of avian relaxin and to immunolocalize relaxin-like
      peptides in the ovary of the hen (Gallus domesticus). A relaxin-like peptide was
      partially purified from ovaries of actively laying hens by size-exclusion
      chromatography and further purified by ion-exchange chromatography on CM
      cellulose. Those fractions containing relaxin immunoreactivity were identified
      with the use of a homologous porcine relaxin radioimmunoassay on selected column
      effluent and pooled, and a sample was subjected to SDS-gel electrophoresis. The
      SDS-gel-separated proteins were electrotransferred onto a nitrocellulose membrane
      and immunostained with an antiserum to porcine relaxin which showed the presence
      of a single band of approximately 6000 daltons. The dose-response curve generated
      by avian relaxin-like peptide in the homologous porcine relaxin radioimmunoassay
      was parallel to that produced by the porcine relaxin standard. Like porcine
      relaxin, avian relaxin-like peptide eluted from the Sephadex G-50 in an elution
      volume for a molecule of approximately 6000 daltons, was retained on CM
      cellulose, and was bioactive in in vitro inhibition of spontaneous contractions
      of estrogen-primed mouse uterus (a relaxin bioassay). Using an antiserum specific
      to porcine relaxin, avian relaxin-like peptide was immunolocalized to the
      granulosa cells of postovulatory follicle from ovary of a hen less than 24 hr
      postoviposition. No immunostaining was detected in the cells of the largest
      preovulatory follicles or when the antiserum was preabsorbed with porcine relaxin
      prior to staining. The finding of this study indicates that the avian
      postovulatory follicle, like the corpus luteum of other vertebrate species
      (sharks and mammals), contains a relaxin-like peptide.

PMID- 9038249
TI  - Identification and characterization of methyl farnesoate binding proteins from
      the crab, Cancer magister.
AB  - Methyl farnesoate (MF) binding proteins were identified in the hemolymph of male
      crabs, Cancer magister, using a tritium-labeled photoaffinity analog of MF,
      farnesyl diazomethyl ketone (FDK). Crab hemolymph was incubated with [3H]FDK in
      the presence of increasing amounts of unlabeled MF and the proteins were
      separated using SDS-PAGE. The associated fluorogram revealed the presence of two
      specific MF binding proteins with apparent molecular masses of 34 and 44 kDa. MF
      binding proteins were not detected in other tissues including testes, eyestalks,
      hepatopancreas, heart, muscle, epidermis, and Y-organs. Unlabeled MF and FDK were
      capable of displacing [3H]FDK from hemolymph MF binding proteins in a dose
      dependent way. The apparent dissociation constant (Kd) of each binding protein
      for MF and FDK was approximately 65 and 100 nM, respectively, as determined by
      saturation binding studies. A ligand binding assay followed by Scatchard analysis
      was used to determine a more accurate apparent Kd value of 145 +/- 10 nM. A
      single MF binding peak was demonstrated when hemolymph samples incubated with
      [3H]FDK were electrophoresed under nondenaturing conditions.

PMID- 9038250
TI  - Molecular evolution of vertebrate VIP receptors and functional characterization
      of a VIP receptor from goldfish Carassius auratus.
AB  - Vasoactive intestinal polypeptide (VIP) is a neuropeptide that has numerous
      physiological actions and is widely distributed in the body. However, as yet,
      there is no sequence information about VIP receptors in lower vertebrates.
      Partial cDNA fragments spanning transmembrane domains 2 to 6 of VIP receptors
      were isolated from six nonmammalian vertebrate species, including chicken,
      pigeon, frog, lizard, salmon, and goldfish. Sequence comparison of these
      receptors revealed essential structural motifs responsible for receptor function.
      In addition, the first nonmammalian full-length VIP receptor cDNA was obtained by
      screening a goldfish brain and pituitary cDNA library. Functional expression of
      this receptor in mammalian COS-7 cells showed that it is coupled to cAMP
      production in a VIP and PACAP concentration-dependent manner; the EC50 of VIP was
      determined to be 1 nM. At 100 nM peptide, the relative potency of various
      peptides in stimulating cAMP in the transfected cells was VIP > PACAP > GHRH =
      secretin > PHM > PTH > glucagon > GLP-1 > GIP. Characterization of the VIP
      receptors in lower vertebrates should enhance our understanding of the molecular
      evolution and physiology of VIP in vertebrates.

PMID- 9038251
TI  - Suppression of apoptosis by gonadotropin, 17beta-estradiol, and epidermal growth
      factor in rainbow trout preovulatory ovarian follicles.
AB  - In this study we present the first evidence for the occurrence of apoptotic cell
      death in ovarian follicles from teleost fish. Preovulatory ovarian follicles from
      mature hatchery-raised rainbow trout (Oncorhynchus mykiss) were collected and
      either immediately frozen in liquid nitrogen or incubated in serum-free medium at
      18 degrees for 24 hr. The extent of ovarian apoptotic DNA fragmentation was
      determined using 3'-end labeling of DNA with [32P]dideoxy-ATP, size fractionation
      by agarose gel electrophoresis, and quantification of low-molecular-weight (<15
      kb) DNA using autoradiography and liquid scintillation counting. The extent of
      apoptotic DNA fragmentation was eightfold greater in immediately frozen
      preovulatory follicles than in previtellogenic ovarian follicles collected from
      immature rainbow trout (P < 0.05), suggesting differences in the degree of
      apoptosis at different stages of follicular development. In preovulatory trout
      follicles, the extent of apoptotic DNA fragmentation was fivefold greater in
      follicles incubated for 24 hr. Treatment of incubated preovulatory follicles with
      either partially purified salmon gonadotropin SG-G100 (1 microg/ml) or epidermal
      growth factor (EGF; 100 ng/ml) suppressed apoptotic DNA fragmentation by 31 and
      41%, respectively, in comparison to untreated incubated follicles (P < 0.01).
      Treatment of incubated follicles with 17beta-estradiol (1-100 ng/ml) caused a
      concentration-dependent suppression of apoptotic DNA fragmentation (P < 0.05).
      These results suggest that apoptosis is involved in teleost ovarian development
      and that several of the hormonal factors acting as follicle survival factors in
      mammalian and avian ovaries may play a similar role in teleost ovarian follicles.

PMID- 9038252
TI  - Isolation, characterization, and radioimmunoassay of Atlantic halibut
      somatolactin and plasma levels during stress and reproduction in flatfish.
AB  - Somatolactin (SL), a recently identified teleost pituitary hormone which is a
      member of the growth hormone/prolactin family, was isolated from pituitary tissue
      of Atlantic halibut (Hippoglossus hippoglossus). Pituitary proteins were
      extracted in ammonium bicarbonate (pH 7.8), fractionated using gel filtration
      chromatography, and purified using reversed-phase high-performance liquid
      chromatography. Halibut SL was identified on the basis of molecular size
      (determined by gel electrophoresis and mass spectroscopy), cross-reactivity of
      the putative hormone with antisera to cod SL, and N-terminal amino acid sequence.
      Polyclonal antibodies to purified halibut SL were raised in rabbits, and a
      radioimmunoassay (RIA) was developed for measurement of plasma concentrations of
      SL using purified halibut SL as a standard. The RIA was tested in several
      flatfish species including Pacific halibut (Hippoglossus stenolepis), English
      sole (Pleuronectes vetulus), and rock sole (Lepidopsetta bilineata). The assay
      was specific for SL as indicated by absence of cross-reactivity with Atlantic
      halibut growth hormone, prolactin, and GTH alpha subunit. Dilutions of plasma and
      pituitary extracts from Pacific halibut, English sole, and rock sole were
      parallel to the Atlantic halibut SL standard curve, indicating that the assay is
      valid for a range of flatfish species. Using halibut SL antiserum, SL was
      localized in the pars intermedia of English sole pituitary, where it has been
      identified in previously examined teleost species. The RIA was used to measure
      plasma levels of SL in Atlantic halibut and English sole during reproductive
      development, and in English sole subjected to various types of environmental
      stressors, including handling and crowding. In both sole and halibut, plasma SL
      concentrations remained relatively constant throughout gonadal development, but
      dropped during or following ovulation. Plasma SL levels in English sole tended to
      increase in response to acute stress, in parallel with plasma cortisol levels.

PMID- 9038253
TI  - Regulation of melatonin synthesis in rainbow trout (Oncorhyncus mykiss) pineal
      organs: effects of calcium depletion and calcium channel drugs.
AB  - The effects of calcium depletion and of three calcium channel drugs on melatonin
      synthesis in pineal organs of rainbow trout (Oncorhyncus mykiss) were examined.
      Dark-induced melatonin synthesis was inhibited by calcium depletion, by treatment
      with nitrendipine (NTR), an antagonist of the L-type voltage-sensitive calcium
      channel, and by treatment with omega-Conotoxin GVIA, an antagonist of the N-type
      voltage-sensitive calcium channel. Bay K 8644, an agonist of the L-type channel,
      had no significant effect on pineal melatonin synthesis. These data represent
      evidence that calcium entry into trout pineal photoreceptor cells through voltage
      sensitive calcium channels is important in the maintenance of dark-induced
      melatonin synthesis and that light's inhibitory effect on melatonin synthesis may
      be mediated by closure of these channels. NTR-induced inhibition of dark-induced
      melatonin synthesis was abolished when dibutyryl cyclic AMP (db-cAMP) was
      administered to NTR-treated pineal organs, suggesting that calcium acts upstream
      of cAMP in regulating melatonin synthesis.

PMID- 9038254
TI  - The effect of chronic testosterone administration on sturgeon gonadotropins in
      juvenile and pre-vitellogenic white sturgeon (Acipenser transmontanus).
AB  - The effects of chronic exogenous testosterone treatment on the synthesis and/or
      secretion of two sturgeon gonadotropins (stGTH I and stGTH II) were assessed in 2
      year-old juvenile white sturgeon (Acipenser transmontanus) surgically implanted
      with silastic capsules filled with 75 mg of testosterone and in previtellogenic
      female white sturgeon females implanted with 150 mg of testosterone. In groups of
      juvenile white sturgeon sacrificed 30, 60, 90, or 442 days postimplantation,
      pituitary concentrations of stGTH I were significantly greater in testosterone
      treated fish (P < 0.01) when compared to those of controls. Pituitary
      concentrations of stGTH II were significantly higher (P < 0.01) in juvenile fish
      treated 60, 90, or 442 days with testosterone when compared to those of controls.
      Exogenous testosterone had no effect on plasma concentrations of either stGTH.
      Additional testosterone-treated juvenile sturgeon which were injected
      intraperitoneally 90 or 442 days postimplantation with 10 microg/kg of the
      gonadotropin releasing hormone analog d-Ala6-des-Gly10-GnRH ethylamide (GnRHa)
      also showed no change in plasma concentrations of stGTHs. Similar results were
      obtained for previtellogenic white sturgeon, as pituitary concentrations of stGTH
      I and stGTH II were significantly greater (P < 0.01) after 60 days of
      testosterone treatment compared to those of controls. A second group of 60-day
      testosterone-treated previtellogenic females also failed to exhibit increases of
      plasma stGTHs when administered 10 microg/kg of GnRHa. These results indicate
      that long-term testosterone treatment stimulates the accumulation of pituitary
      stGTHs in both juvenile and previtellogenic white sturgeon but does not affect
      basal or GnRHa-induced stGTH secretion.

PMID- 9038255
TI  - A steroidal pheromone and spawning stimuli act via different neuroendocrine
      mechanisms to increase gonadotropin and milt volume in male goldfish Carassius
      auratus.
AB  - In goldfish (Carassius auratus), pheromonal 17alpha, 20beta-dihydroxy-4-pregnen-3
      one (17,20beta-P) and spawning stimuli (interaction with a sexually active female
      releasing prostaglandin pheromone) both increase gonadotropin-II (GtH-II) and
      milt volume. In the goldfish pituitary, GtH-II release is stimulated by
      gonadotropin-releasing hormone (GnRH) and inhibited by dopamine (DA). In this
      study, we investigated the possibility that 17,20beta-P and spawning stimuli act
      via separate neuroendocrine mechanisms by determining whether their effects on
      GtH-II could be selectively disrupted by injection of DA type-2 receptor (D-2)
      agonists (bromocryptine and LY171555) or a goldfish GnRH antagonist, [Ac-Delta3
      Pro1, 4FD-Phe2, d-Trp3,6]-mGnRH (analog E). D-2 agonists blocked 17,20beta-P
      induced increases in GtH-II and milt volume but did not affect spawning-induced
      responses. GnRH antagonist blocked 17,20beta-P-induced increases in GtH-II and
      milt volume, and spawning-induced GtH-II increase, but did not affect spawning
      induced increase in milt volume. These results suggest that (1) pheromonal
      17,20beta-P and spawning stimuli increase GtH-II increase via distinct
      neuroendocrine mechanisms, (2) the effect of pheromonal 17,20beta-P on increasing
      milt volume is GtH-II-dependent, and (3) the effect of spawning stimuli on
      increasing milt volume is GtH-II-independent.

PMID- 9038256
TI  - Opioid effects on macrovascular dopamine release.
AB  - Both alkaloid opiates and met-enkephalin occur in vertebrate chromaffin cells,
      where they affect catecholamine (CA) secretion. Since the large blood vessels of
      the eel and the rat release dopamine (DA) from as yet unidentified source(s), we
      studied the impact of alkaloid opiates and met-enkephalin on the secretion of DA
      from three macrovessels of the American eel (Anguilla rostrata) in a perifusion
      system. Codeine, morphine, and met-enkephalin increased the release of DA from
      both the ventral aorta and the caudal vein. The antagonist naloxone stimulated DA
      release from the caudal vein, but had no impact on release from the ventral
      aorta. Only codeine had a significant effect on DA release from the posterior
      cardinal vein. These findings show that the DA release from the macrovessels is
      sensitive to opioid substances, and they suggest that the antagonistic effects
      between alkaloid opiate and opioid peptide, seen in other systems, are absent in
      large blood vessels. Furthermore, the "unorthodox" stimulatory effect of naloxone
      in the caudal vein raises the question of as yet unidentified receptor and/or
      effector systems.

PMID- 9038257
TI  - Effect of gonadal steroid hormones on plasma growth hormone concentrations in
      sexually immature rainbow trout, Oncorhynchus mykiss.
AB  - In the present study we investigated the effects of gonadal steroid hormones on
      plasma growth hormone (GH), triiodothyronine (T3), and thyroxine (T4) levels in
      steroid-primed sexually immature rainbow trout, Oncorhynchus mykiss, in order to
      determine whether changes in plasma GH and thyroid hormone levels during sexual
      maturation are a result of elevated gonadal steroid levels or are an altered
      condition associated with reproduction (as proposed by Sumpter et al., 1991b). We
      found no significant correlation between plasma GH and condition factor in either
      of two cohorts of rainbow trout (1+ and 2+ year old fish) examined. To evaluate
      the effects of gonadal steroids on plasma GH and thyroid hormone levels, fed and
      fasted (4 weeks fasted) fish were given a slow-release implant of testosterone
      (T), 17beta-estradiol (E2), 17alpha-methyltestosterone (17alphaMT), or 5alpha
      dihydrotestosterone (5alphaDHT) dissolved in coconut oil, or coconut oil alone
      (control). Blood samples were taken after 2 weeks and analyzed for GH, T3, and
      T4. Neither 17alphaMT nor 5alphaDHT had any effect on plasma GH levels in fed or
      fasted fish. However, plasma GH levels were elevated after E2 treatment in both
      fed and fasted (P </= 0.01) fish, and after T treatment in fasted but not fed
      fish (P < 0.01). The effects of gonadal steroid hormones on thyroid hormone
      levels were less clear. T3 levels were depressed in fed E2-primed fish (P < 0.05)
      and elevated in fasted T- and 17alphaMT-primed fish (P < 0.05). T4 levels were
      depressed in T- and 5alphaDHT-primed fed fish (P < 0.01) and elevated in fasted
      E2-primed fish (P < 0.01). These elevated GH levels associated with sexual
      maturation may be more clearly linked to elevated gonadal steroid levels rather
      than to changes in nutritional status. The effects of gonadal steroids on thyroid
      hormone levels are less clear.

PMID- 9038258
TI  - Steroids modulate the excitability of crayfish (Procambarus digueti)
      photoreceptors: long- and short-term actions.
AB  - Short- and long-term actions of the steroids corticosterone, progesterone, and
      ecdysterone were analyzed upon excitability of crayfish retinular cells. The
      three hormones showed short-term actions, particularly during photoreceptor dark
      adaptation; effects were found to be dependent on the hour of the day.
      Corticosterone and progesterone had similar effects, i.e., resembled dark-adapted
      conditions; ecdysterone actions were opposite and resembled light adaptation.
      Long-term effects were opposed to short-term effects in all cases. Possible
      mechanisms underlying these effects are discussed.

PMID- 9038259
TI  - Circadian melatonin rhythms in cultured zebrafish pineals are not affected by
      catecholamine receptor agonists.
AB  - Catecholamine receptors of multiple classes have been shown to influence pineal
      melatonin synthesis in a species-specific manner. In these experiments, the
      effects of catecholamine receptor agonists on circadian melatonin rhythms of
      zebrafish (Danio rerio) pineal in vitro were examined. Cyclic application of
      adrenergic receptor agonists (norepinephrine, phenylephrine, clonidine, and
      isoproterenol) had no effect on zebrafish pineal melatonin release, nor on the
      circadian oscillator that regulates melatonin rhythms. Pineal melatonin release
      was partially suppressed by quinpirole, a D2 dopamine receptor agonist, but
      cyclic application of quinpirole did not reset the pineal circadian oscillator.
      Pineal melatonin release was unaffected by either dopamine or SKF38393, a D1
      receptor agonist, suggesting that the effects of quinpirole were not mediated by
      dopamine receptors. The regulatory mechanisms underlying pineal melatonin rhythms
      appear to differ among teleosts.

PMID- 9038260
TI  - Photoperiodic condition modulates the effects of testosterone on song control
      nuclei volumes in male European starlings.
AB  - Songbirds possess a specialized network of brain nuclei mediating song learning
      and production, the song system. In many species, the nuclei in this circuit are
      larger in volume in males housed on long photoperiods than in males housed on
      short photoperiods. Exposure to long days initially leads to increases in
      circulating levels of testosterone (T) and it is generally believed that volume
      changes in the song system are controlled by T-dependent effects of photoperiod.
      However, a growing body of evidence indicates that photoperiod can also have T
      independent effects on song system morphology. Previous work in our laboratory
      suggested that photoperiodic condition may modulate the effects of exogenous
      testosterone on the volumes of song control nuclei in male European starlings
      (Sturnus vulgaris). In the present report, we tested the hypothesis that
      photorefractoriness attenuates the effects of T on the volumes of song control
      nuclei in starlings. One group of long-day photorefractory males (16L:8D) was
      exposed to exogenous T and two groups of short-day photosensitive birds (8L:16D)
      were either implanted with T or blank (control) capsules. After 8 weeks, T levels
      were elevated in both groups of T-implanted birds and were undetectable in
      control animals. Volumes of the high vocal center were larger in T-implanted
      photosensitive birds than in both T-implanted photorefractory and control
      photosensitive males, which did not differ. These results suggest that
      photorefractoriness renders the song nuclei of starlings less sensitive to
      stimulatory effects of T. Plasticity in the starling song system appears to
      require the coordination of the appropriate hormonal milieu with a permissive
      photoperiodic condition.

PMID- 9038262
TI  - Discoveries in the cell cycle and ovarian cancer.

PMID- 9038263
TI  - Overexpression of cyclin D1 in epithelial ovarian cancers.
AB  - Amplification and overexpression of the cell cycle-related gene cyclin D1 have
      been demonstrated in several human malignancies and have been shown to be
      directly oncogenic in breast epithelium and lymphocytes. Overexpression of the
      gene can occur in the absence of gene amplification. We have investigated whether
      cyclin D1 is overexpressed in a panel of 43 sporadic epithelial ovarian cancers
      using immunohistochemistry. Cyclin D1 was overexpressed in 26% of these tumors.
      Overexpression of cyclin D1 is associated with borderline or well-differentiated,
      grade 1 tumors but does not correlate with a particular histological type,
      overexpression of the c-erb-B2 oncogene, or presence of estrogen receptors. It is
      suggested that overexpression of cyclin D1 may contribute to the pathogenesis of
      epithelial ovarian cancers, including a subset of tumors different from those
      overexpressing the c-erb-B2 oncogene.

PMID- 9038264
TI  - Hereditary ovarian cancer: molecular genetics and clinical implications.
AB  - Epidemiologic data support the existence of two discrete manifestations of
      hereditary ovarian carcinoma: the breast and ovarian cancer syndrome and the
      hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. Genetic linkage
      analyses reveal that the majority of breast and ovarian cancer families are
      linked to the BRCA1 gene, while some cases of hereditary ovarian cancer are also
      apparent in breast cancer families linked to the BRCA2 gene. The majority of
      HNPCC families are linked to one of four genes encoding a family of DNA mismatch
      repair proteins. Molecular analyses demonstrate that genetic screening for
      germline transmission of a defective allele of one or another of these genes is
      now possible for high-risk individuals. The ethical, legal, and social
      implications of this type of analysis are multiple and complex, and genetic
      counseling requires a thorough understanding of these issues and a cautious
      approach to most effectively meet the special needs of this patient population.
      Increased medical surveillance and prophylactic oophorectomy are among the
      management options that may be appropriate for some genetically predisposed,
      asymptomatic women. Further research is needed regarding the most effective use
      of this genetic information in formulating counseling and clinical management
      strategies.

PMID- 9038266
TI  - Cumulative risk of second primary cancers in women with index primary cancers of
      uterine cervix and incidence of lower anogenital tract cancers, Michigan, 1985
      1992.
AB  - A retrospective cohort study of women with cancers of the lower anogenital tract
      was derived from the Michigan Tumor Registry records for the years 1985-1992.
      Incidence rates of invasive cervical, vulvar, vaginal and anal cancers were
      analyzed with respect to age, race, year of diagnosis, stage at diagnosis, and
      histopathology. The incidence of metachronous primary cancers following initial
      primaries of the cervix was also investigated. Anogenital cancers constituted
      about 4% of all cancers in Michigan women between 1985 and 1992. Age-adjusted
      incidence rates per 100,000 women per year for each site were found to be as
      follows: 10.1 (cervix), 1.9 (vulva), 1.0 (vagina), and 0.6 (anus). The incidence
      rates of women in the United States for cancers in the anogenital region were
      higher in blacks than in whites, with the exception of vulvar cancer. U.S. blacks
      were more likely to develop squamous cell carcinomas, but less likely to develop
      adenocarcinomas of the cervix and vagina when compared to whites. Over the 5- to
      8-year follow-up period, 6.5% of the women with index cases of cervical cancer
      developed second primary cancers. This represented a 40% increase in the risk of
      incident primary cancers compared to the risk in the general population of
      Michigan women. The significant occurrence of second primaries of the vagina
      following index primaries of the cervix suggests a shared etiology, such as
      infection with human papillomavirus. The incidences of cancers related to
      smoking, including cancers of the urinary bladder, lung/bronchus, and lower
      anogenital tract were also increased.

PMID- 9038265
TI  - Antibody levels against alpha-galactosyl epitopes in sera of patients with
      squamous intraepithelial lesions and early invasive cervical carcinoma.
AB  - We measured serum levels of anti-Gal(alpha 1-->3)Gal and anti-Gal(alpha 1-->2)Gal
      antibodies in 89 and 91 women, respectively, by using ELISA. These patients had
      cervical intraepithelial neoplasia (CIN) grades 1 to 3 and early invasive
      cervical carcinoma (ICC). Our objective was to compare anti-alpha-galactosyl
      antibody levels among them and with those of normal controls. High levels of anti
      Gal(alpha 1-->2)Gal antibodies were detected in 22% of patients (P = 0.006). The
      mean level was 1.6 times greater than that of controls, without difference among
      subgroups. Thirty percent of patients had abnormally high anti-Gal levels (P =
      0.001). Mean levels were twofold greater than the mean control value. Subsets
      with human papillomavirus/CIN 1 and CIN 2-3 had high immunoreactivity (P =
      0.004). Both antibodies showed a significant correlation (r = 0.53, P < 0.00001).
      We conclude that 22 to 30% of patients with CIN 1-3 showed significantly high
      levels of anti-alpha-galactosyl antibodies. This seroreactivity might be related
      to the abnormal expression of alpha-galactosyl residues at some point of the
      natural history of human papillomavirus infection of the uterine cervix,
      suggesting an active immune response by natural antibodies against this virus.
      Further studies are needed to determine whether anti-alpha-galactosyl antibodies
      confer protection in human papillomavirus infection.

PMID- 9038267
TI  - Intra- and perioperative complications associated with tandem and colpostat
      application for cervix cancer.
AB  - PURPOSE: The purpose of this study was to chronicle the acute morbidity
      associated with the implantation of tandems and colpostats in women with
      carcinoma of the cervix; to determine factors that predispose to the development
      of such complications; and to assess whether the use of ultrasound allowed the
      apparatus to be safely implanted in women at relatively high risk for perforation
      of hollow viscous organs. METHODS: A database from two Philadelphia institutions
      was used to assess the aforementioned factors among 143 tandems/colpostats
      inserted into 100 women with cervix cancer. Twenty patients had insertion under
      ultrasound guidance because of stenotic cervical os, fibrosis from external-beam
      irradiation, indeterminate orientation of endometrial cavity axis, or previous
      perforation. Univariate and multivariate analyses were performed to identify
      predictors of intra- and perioperative complications. RESULTS: Intraoperative
      complications occurred in 7 of 143 placements (5%). These included uterine
      perforations (n = 4), vaginal lacerations (n = 2), and one instance of bladder
      perforation. Only older age, whether entered as a continuous or a dichotomous
      variable, was associated statistically with these complications. Perioperative
      complications (e.g., fever, bowel obstruction, exacerbation of chronic
      obstructive pulmonary disease, cardiac complication) occurred in 54 of 143
      implanted women. In univariate analysis, older age and underlying chronic
      obstructive pulmonary disease (COPD) appeared to be associated with perioperative
      complications. A multivariate analysis showed that underlying COPD predisposed to
      perioperative complications during the first implant and that age over 60 years
      independently predicted for complications during any implant. CONCLUSIONS:
      Intraoperative complications are relatively rare events. Ultrasonography seems to
      allow safe intrauterine insertion of the tandem despite the selection of
      difficult cases for this adjunctive imaging tool. Patient age over 60 years
      independently predicts for perioperative complications. COPD predicts for
      perioperative complications during the first but not the second implant, implying
      that physicians are able to optimize the medical management of pulmonary disease
      to allow a second implant to be performed more safely.

PMID- 9038268
TI  - Polarographic measurement of pO2 in cervix carcinoma.
AB  - The outcome of radiation therapy of cervix carcinoma might depend on the
      oxygenation of the tumor tissue. An adequate method for measurement of tumor
      oxygen tension (pO2) is therefore needed. The purpose of the work reported here
      was dual: (1) to investigate whether polarographic pO2 measurements with the
      Eppendorf pO2 Histograph 6650 are sufficiently sensitive to detect differences in
      tumor pO2 before and after blood transfusion of anemic patients and between
      poorly and well-vascularized tumor tissue, and (b) to investigate whether
      accurate tumor, pO2 measurements require extensive mapping of tumor temperature
      and the avoidance of anesthesia. Nineteen patients with squamous cell carcinoma
      of the uterine cervix FIGO stages Ib to IVb were included in the study. Vascular
      density was determined by histological examination of tumor biopsies. Propofol
      was used as a single anesthetic agent. Tumor pO2 distributions recorded before
      and after the administration of propofol were not different (P > 0.05). The
      temperatures measured in the tumor periphery and center did not differ from the
      rectal temperature (P > 0.05), suggesting that tumor pO2 measurements can be
      based on the rectal temperature. Increased hemoglobin concentrations after blood
      transfusion resulted in increased tumor oxygenation in 50% of the patients (P <
      0.001). The pO2 frequency distributions of the susceptible tumors showed
      increased 50th percentiles but unchanged 10th percentiles, suggesting that
      transfusion cannot reduce the fraction of radiation-resistant hypoxic tumor cells
      extensively. Tumor tissue with high vascular density showed higher pO2 values
      than tumor tissue with low vascular density (P < 0.001). In conclusion,
      polarographic measurement of tumor pO2 with the Eppendorf pO2 Histograph 6650 is
      a sensitive method for assessment of the oxygenation of cervix carcinoma.
      Reliable tumor pO2 measurements can be performed in patients given propofol
      anaesthesia and without extensive mapping of tumor temperature.

PMID- 9038269
TI  - The effect of sartorius transposition on wound morbidity following inguinal
      femoral lymphadenectomy.
AB  - In spite of efforts to reduce complications associated with inguinal-femoral
      lymphadenectomy (IFL), morbidity continues to be substantial. We sought to assess
      the efficacy of sartorius transposition (ST) in reducing groin wound
      complications following IFL, in patients with vulvar malignancy. The records of
      101 patients with vulvar cancer undergoing IFL through separate incisions between
      March 1975 and December 1994 were examined. Sixty-two patients undergoing ST
      (group 1) were compared to 38 who did not (group 2). The groups were similar with
      respect to age, weight, tobacco/alcohol use, prior abdominal/vulvar surgery,
      prevalence of diabetes, hypertension, or peripheral vascular disease, and
      previous exposure to irradiation or chemotherapy. Additionally, there was no
      significant difference with respect to extent of disease, incidence of macro
      /microscopic groin metastases, use of groin drains, and use of perioperative
      antibiotics or deep venous thrombosis prophylaxis. Groin wound complications were
      less frequent in patients undergoing ST (group 1). The incidence of groin
      cellulitis was 30% in group 1 compared with an incidence of 58% in group 2 (P =
      0.011). Significant groin wound morbidity, defined as either wound breakdown or
      cellulitis, was seen less frequently in group 1 (41% vs 66%; P = 0.029).
      Employing a multivariate analysis, only patient weight < 150 lbs and performance
      of ST were established as independently associated with a reduction in groin
      morbidity following IFL (P = 0.0281 and P = 0.0075, respectively). In conclusion,
      despite waning enthusiasm for its performance, ST appeared to significantly
      reduce the incidence of wound morbidity after IFL. Our data confirmed that
      separate incisions, and improved perioperative antibiotics, have not eliminated
      the value inherent in this surgical modification. We suggest a prospective trial
      to further establish the benefit of sartorius transposition during IFL.

PMID- 9038271
TI  - A pure brain metastasis of choriocarcinoma from a mixed germ cell tumor of the
      ovary.
AB  - We report a pure brain metastasis of choriocarcinoma from a mixed germ cell tumor
      of the ovary in a 19-year-old patient. This condition is extremely rare.
      Following abdominal operative procedures, multiple courses of combination
      chemotherapy, and resection of chemotherapy-resistant pulmonary metastases, a
      brain metastasis developed during chemotherapy. Craniotomy with resection of the
      neoplasm, brain radiation, and further chemotherapy was followed by disappearance
      of a pulmonary metastasis and long-term survival of the patient.

PMID- 9038270
TI  - Molecular characterization of adenocarcinoma of the cervix.
AB  - In an attempt to characterize the molecular alterations of cervical
      adenocarcinoma, we analyzed 32 paraffin-embedded specimens for the presence of K
      ras mutations, p53 overexpression, p16 and Rb protein expression, and the
      presence of HPV 16 and 18 DNA. Overall 25/32 (78%) of the tumors displayed an
      abnormality in at least one of these analyses. K-ras mutations were detected by
      PCR amplification and RFLP analysis in 3 tumors, including 2 at codon 12 and 1 at
      codon 61. p53 overexpression determined by immunohistochemistry was demonstrated
      with > 80% of tumor nuclei staining in 4 cases, 10-15% of nuclei staining in 3
      cases, and < 1% of nuclei staining in 5 cases. The pattern of staining was
      diffuse in 6 cases, focal in 1 case, and scattered in 5 cases. Analysis of p16
      protein expression in 23 specimens revealed 1 tumor with abnormal staining, while
      Rb protein expression was determined to be normal in all 25 tumors tested. HPV
      DNA, detected by PCR with type-specific primers, was found in 16 tumors (50%),
      including 7 (22%) with HPV 16 and 9 (28%) with HPV 18. There was no correlation
      among these abnormalities except that the presence of HPV and strong p53
      overexpression (> 80% tumor nuclei staining) were mutually exclusive events.
      Clinical correlation demonstrated that p53 overexpression involving the majority
      of tumor cell nuclei is characteristic of advanced stage disease, while HPV
      positivity and activated ras genes are associated with early stage disease.

PMID- 9038272
TI  - Turbo-gracilis myocutaneous flap for perineal reconstruction.
AB  - The turbo-gracilis flap, which has been described previously for the purpose of
      extending the unreliable gracilis skin island, and previously applied in forearm
      reanimation surgery, is now adapted for reconstruction in the perineal region. We
      present a case report of a patient with previous vulvar carcinoma treated with
      resection and radiation who presented with a very large defect of the perineal
      region. Reconstruction was carried out using a turbo-gracilis flap. The
      advantages of the flap are well demonstrated in the successful reconstruction, in
      that it provides an extensive amount of well-vascularized tissue due to an
      extended gracilis skin island which is vascularized by way of a vein graft from
      the proximal pedicle blood supply to a distal gracilis pedicle which, in turn,
      supplies the extended skin island. This allows an extensive amount of tissue to
      be harvested from a single donor site and ensures the viability of the skin
      island. A review of the advantages and disadvantages of various types of perineal
      reconstruction is also presented and contrasted with the turbo-gracilis method.

PMID- 9038273
TI  - Endolymphatic stromal myosis associated with tamoxifen use.
AB  - A case of low-grade endometrial stromal sarcoma (endolymphatic stromal myosis)
      occurring in a patient who had received tamoxifen citrate for 3 years following
      surgical treatment for breast cancer is presented. Endometrial adenocarcinomas
      have been the most frequently reported tumor associated with tamoxifen use. More
      recently, uterine sarcomas have also been described in association with the use
      of tamoxifen. This report adds only the second case of a low-grade endometrial
      stromal sarcoma associated with tamoxifen use. As in the first report, the tumor
      demonstrated a sex-cord-like pattern of differentiation, an uncommon feature of
      endometrial stromal sarcomas. This suggests a possible association between
      tamoxifen use and the subsequent development of low-grade endometrial stromal
      sarcoma.

PMID- 9038274
TI  - Treatment of stage IV "high-grade" endometrial stromal sarcoma with ifosfamide,
      adriamycin, and cisplatin.
AB  - A 46-year-old woman with stage IV "high-grade" endometrial stromal sarcoma
      presented with massive uterine bleeding and dyspnea. Her WHO performance status
      was grade 4. After chemotherapy consisting of ifosfamide, Adriamycin, and
      cisplatin, the uterus shrank from 20 x 15 x 15 to 6 x 6 x 8 cm and multiple
      pulmonary nodules almost completely disappeared. The PO2 increased from 57.8 to
      89.3 mmHg and her performance status improved to grade 0, making it possible for
      pelvic surgery to be performed. At 10 months postoperatively, there was no
      evidence of disease. This case suggests that IAP might be effective chemotherapy
      for patients with high-grade endometrial stromal sarcoma.

PMID- 9038275
TI  - Adenocarcinoma of the ileum with an enterotubal fistula presenting as an adnexal
      mass.
AB  - Small bowel adenocarcinomas account for 3% of gastrointestinal malignancies, and
      20 to 25% of these arise in the ileum. Clinical presentation is variable, and
      early diagnosis is difficult. A 56-year-old postmenopausal woman presented with
      crampy abdominal pain, anorexia, and weight loss. Pelvic examination and
      ultrasound revealed a 6 x 8-cm complex right adnexal mass. At laparotomy, en bloc
      resection of the right adnexa and the densely adherent ileal segment was
      performed along with a hysterectomy and a left salpingo-oophorectomy. The final
      pathology showed a moderately differentiated invasive adenocarcinoma of the ileum
      with a malignant enterotubal fistula. This is the first case reported in the
      literature of an ileal adenocarcinoma with a tubal fistula masquerading as an
      adnexal mass.

PMID- 9038276
TI  - Primary choriocarcinoma of the uterine cervix: clinical, MRI, and color Doppler
      ultrasonographic study.
AB  - Primary choriocarcinoma of the uterine cervix was diagnosed in a 38-year-old
      Japanese woman 4 months after a normal vaginal, term delivery. The patient had
      experienced irregular genital bleeding for several weeks. A cervical polypoid
      tumor was detected by visual inspection 4 months after delivery. Magnetic
      resonance imaging (MRI) and color Doppler ultrasonography revealed a
      hypervascular tumor (6 cm) in the uterine cervix. The patient's urinary level of
      human chorionic gonadotropin (hCG) was 128,000 IU/L. Histological examination of
      a biopsy of the cervical tumor showed choriocarcinoma. After completion of 2
      courses of chemotherapy, the patient underwent a total abdominal hysterectomy.
      Histological examination of uterus showed no evidence of choriocarcinoma. At
      present, the patient is free of disease. MRI and color Doppler ultrasonography
      were useful for diagnosis by detecting the abundant blood flow and central
      necrosis of the cervical tumor.

PMID- 9038277
TI  - Ovarian serous papillary cystadenocarcinoma stage IIIC in a 19-year-old.
AB  - In mature women, the most common histological cell type of ovarian cancer is of
      epithelial origin. In children and adolescents, germ cell tumors are the most
      frequent. We report a case of a serous papillary cystadenocarcinoma FIGO stage
      IIIC in a 19-year-old female. She presented with a 6-month history of vague lower
      abdominal pain. Preoperative CA-125 was elevated at 296 kU/liter. At laparotomy,
      she was found to have stage IIIC disease. A debulking procedure including total
      abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph
      node sampling was performed. The immediate postoperative course was complicated
      by fulminant disseminated intravascular coagulopathy. She was subsequently
      treated with six courses of cyclophosphamide and carboplatin. Twenty-four months
      after surgery, the patient has no evidence of disease despite an increased CA-125
      of 51 kU/liter.

PMID- 9038278
TI  - Management of advanced juvenile granulosa cell tumor of the ovary.
AB  - Juvenile granulosa cell tumors (JGCTs) of the ovary are rare. They usually
      present in children and adolescents. About 90% are diagnosed in early stage (FIGO
      I) with a favorable prognosis. More advanced stages (FIGO II-IV) have a poor
      clinical outcome. We report two cases of short-term, disease-free survival of
      teenagers with Stage III JGCTs treated with aggressive debulking and thorough
      staging but conservative surgery relative to the uterus and contralateral tube
      and ovary plus carboplatin and etoposide chemotherapy. These results are
      encouraging, but the best treatment for extensive and recurrent disease has yet
      to be determined.

PMID- 9038279
TI  - Radiation myelopathy after chemotherapy and radiation therapy for fallopian tube
      carcinoma.
AB  - Radiation myelopathy is a severe consequence of radiation to the spinal cord
      which rarely occurs with standard doses of radiation. This entity commonly
      results in different degrees of sensory and motor deficits. Diagnosis of
      radiation myelopathy in women with gynecologic malignancies may increase with the
      concomitant use of chemotherapy and radiation therapy. This paper reports the
      effect of this combination therapy in a 60-year-old woman with fallopian tube
      carcinoma.

PMID- 9038280
TI  - The activity in human areas V1/V2, V3, and V5 during the perception of coherent
      and incoherent motion.
AB  - We have used the technique of positron emission tomography to study and compare
      the cortical activity produced when humans view a pattern of small squares moving
      incoherently with respect to one another and when the same pattern moves
      coherently and unidirectionally. A stationary version of the stimulus acted as a
      control. Our choice of paradigm was inspired by psychophysical models and
      physiological studies in the macaque monkey which show that directionally
      selective cells in V5 respond optimally to unidirectional coherent motion,
      whereas those of V1 respond to motion within their receptive fields, regardless
      of the motion in surrounding parts. Our results show that human V1/V2, V3, and V5
      are all activated by both types of motion stimuli. Incoherent motion, however,
      proved to be more effective than coherent motion in activating V1/V2 and V5. Thus
      the higher perceptual salience of unidirectional coherent motion in comparison to
      incoherent motion is not reflected by any increased activation of human area V5.

PMID- 9038281
TI  - Brainvox: an interactive, multimodal visualization and analysis system for
      neuroanatomical imaging.
AB  - A study of cognition emerging from a neurobiological perspective, as opposed to
      one emerging from a purely computational or psychological perspective, begins
      with observations of the human brain in normal and pathological states and is
      furthered by the investigation of hypotheses which are articulated using
      neuroanatomical nomenclature. Brainvox is an interactive three-dimensional brain
      imaging software package designed to permit such research through the support of
      the description and quantification of brain pathology in magnetic resonance
      images and of the experimental investigation of human cognition in lesion and
      functional imaging studies. Important general features of Brainvox, for these
      purposes, are: (1) adaptation of volume rendering for brain lesions and for
      corendered datasets; (2) shared memory architecture, which enables the user to
      identify and label anatomical structures, while inspecting the brain in multiple
      views simultaneously; (3) modular program design, including interlocking command
      line utilities, which make Brainvox extensible and empower users without
      programming expertise to implement new analysis techniques through Unix shell
      scripting; and (4) full integration of three-dimensional tools for visualization
      with tools for analysis. Specific features include a new object templating
      technique (MAP-3) for studies of groups of brain-lesioned subjects, a complete
      and extensible suite of command-line processing utilities, a three-dimensional
      optimal graph-searching tool, and a method for planning PET slices and matching
      MR and PET slices (MP_FIT).

PMID- 9038282
TI  - Mutual information for automated unwarping of rat brain autoradiographs.
AB  - An automated multimodal warping based on mutual information metric (MI) as a
      mapping cost function is demonstrated. Mutual information (I) is calculated from
      a two-dimensional (2D) gray scale histogram of an image pair, and MI (= -I)
      provides a matching cost function which can be effective in registration of two-
      or three-dimensional data sets independent of modality. Most histological image
      data, though information rich and high resolution, present nonlinear deformations
      due to the specimen sectioning and need reconstitution into deformation-corrected
      volumes prior to geometric mapping to an anatomical volume for spatial analyses.
      Section alignment via automatic 2D registrations employing MI as a global cost
      function and thin-plate-spline (TPS) warping is applied to deoxy-D-[14C]glucose
      autoradiographic image slices of a rat brain with video reference images of the
      uncut block face to reconstitute a cerebral glucose metabolic volume data. Unlike
      the traditional feature-based TPS warping algorithms, initial control points are
      defined independently from feature landmarks. Registration quality using
      automated multimodal image warping is validated by comparing MIs of the image
      pair registered by automated affine registration and manual warping method. The
      MI proves to be a robust objective matching cost function effective for automatic
      multimodality warping for 2D data sets and can be readily applied to volume
      registrations.

PMID- 9038283
TI  - The relevance of sensory input for the cerebellar control of movements.
AB  - The performance of a motor task not only requires subjects to plan, prepare, and
      initiate but also to monitor how a movement is performed. We used positron
      emission tomography to examine to what extent the human cerebellum is involved in
      controlling motor output or sensory input from movements in normal subjects. In
      the first study, we compared the active performance of a motor task (flexion and
      extension of the right elbow) to the passive execution of the same movements.
      Passive movements were driven by a motor with the arm fixed in a guide hinge.
      Active movements (compared to rest) elicited increases of rCBF mainly in the
      ipsilateral neocerebellar hemisphere and vermis of the posterior lobe. During
      passive movements, almost identical parts of the cerebellar hemispheres and
      vermis were activated (compared to the rest condition). The direct comparison of
      active and passive movement conditions revealed a small activation of the
      neocerebellar hemisphere of the posterior lobe and cerebellar nuclei ipsilateral
      to the movement. Approximately 90% of cerebellar neuronal activity was related to
      sensory input. In the second study, we compared the execution of a free selection
      joystick movement task to a condition in which subjects simply imagined the
      movements. The execution of movements (compared to rest) was associated with
      increases of rCBF in the ipsilateral neocerebellar hemisphere and vermis of the
      posterior lobe. During movement imagination, a small part of the ipsilateral
      cerebellar hemisphere and vermis of the posterior lobe was activated (compared to
      rest). The increase of rCBF during movement imagination accounted for only 20% of
      the signal seen during movement execution. Our results indicate that the
      neocerebellum may be much more concerned with sensory information processing than
      has been considered previously.

PMID- 9038284
TI  - A parametric study of prefrontal cortex involvement in human working memory.
AB  - Although recent neuroimaging studies suggest that prefrontal cortex (PFC) is
      involved in working memory (WM), the relationship between PFC activity and memory
      load has not yet been well-described in humans. Here we use functional magnetic
      resonance imaging (fMRI) to probe PFC activity during a sequential letter task in
      which memory load was varied in an incremental fashion. In all nine subjects
      studied, dorsolateral and left inferior regions of PFC were identified that
      exhibited a linear relationship between activity and WM load. Furthermore, these
      same regions were independently identified through direct correlations of the
      fMRI signal with a behavioral measure that indexes WM function during task
      performance. A second experiment, using whole-brain imaging techniques, both
      replicated these findings and identified additional brain regions showing a
      linear relationship with load, suggesting a distributed circuit that participates
      with PFC in subserving WM. Taken together, these results provide a "dose-response
      curve" describing the involvement of both PFC and related brain regions in WM
      function, and highlight the benefits of using graded, parametric designs in
      neuroimaging research.

PMID- 9038285
TI  - Functional anatomy of human auditory attention studied with PET.
AB  - Positron emission tomography was used to investigate the functional anatomy of
      selective auditory attention in 17 right-handed male volunteers who submitted to
      different tasks: silent rest (REST) listening to frequent low- or rare high
      pitched tones (LIS) delivered randomly to the right or the left ear, selective
      auditory attention where subjects had to attend to deviants in one ear, right
      (ATTR) or left (ATTL). Six subjects had the series REST, LIS, ATTR twice, eight
      subjects the series REST, LIS, ATTL, and the last three subjects the sereis REST,
      ATTR, ATTL. Event-related potentials were simultaneously recorded with PET and
      showed significant task and electrode site effects on the N100 amplitude. When
      compared to REST, LIS elicited bilateral temporal activations of the Heschl's
      gyri and the planum temporale, with a significant rightward asymmetry, and of the
      posterior part of the superior temporal gyrus. Significant right precentral and
      anterior cingulate gyri normalized regional cerebral blood flow increases were
      observed in the frontal lobe. Both the ATTR and the ATTL conditions, compared to
      LIS, activated the supplementary motor area, bilateral precentral, and left
      postcentral cortices without any temporal cortex activation. In addition, the
      ATTL condition resulted in a right prefrontal cortex activation. Pooling the 14
      subjects revealed an asymmetry in the superior temporal gyrus favoring the cortex
      contralateral to the attended ear. Two major networks seem thus to be involved
      during selective auditory attention: (1) a local temporal network, on which
      selective attention produces a modulation of the functional lateralization, and
      (2) a frontal network that could mediate the temporal cortex modulation by
      attention.

PMID- 9038286
TI  - Equivalent responses to lexical and nonlexical visual stimuli in occipital
      cortex: a functional magnetic resonance imaging study.
AB  - Stimulus-related changes in cerebral blood oxygenation were measured using high
      resolution functional magnetic resonance imaging sequentially covering visual
      occipital areas in contiguous sections. During dynamic imaging, healthy subjects
      silently viewed pseudowords, single false fonts, or length-matched strings of the
      same false fonts. The paradigm consisted of a sixfold alternation of an
      activation and a control task. With pseudowords as activation vs single false
      fonts as control, responses were seen mainly in medial occipital cortex. These
      responses disappeared when pseudowords were alternated with false font strings as
      the control and reappeared when false font strings instead of pseudowords served
      as activation and were alternated with single false fonts. The string-length
      contrast alone, therefore, is sufficient to account for the activation pattern
      observed in medial visual cortex when word-like stimuli are contrasted with
      single characters.

PMID- 9038287
TI  - Protective immunity against Salmonella typhimurium elicited in mice by oral
      vaccination with phosphorylcholine encapsulated in poly(DL-lactide-co-glycolide)
      microspheres.
AB  - Encapsulation of vaccines in biodegradable microspheres provides excellent
      mucosal immunogens with a high potential for immunization against bacterial
      infections. We tested the protective immunity elicited by intragastric
      vaccination with phosphorylcholine (PC) encapsulated in poly(DL-lactide-co
      glycolide) (DL-PLG) microspheres against Salmonella typhimurium in a mouse model
      of invasive intestinal infection. We chose PC as the antigen because it was found
      to elicit an immune response after intestinal exposure of mice to PC-bearing S.
      typhimurium and because anti-PC immunity protects mice against Streptococcus
      pneumoniae, another PC-bearing microorganism. Mice were primed intragastrically
      on days 1, 2, and 3 and boosted on days 28, 29, and 30 with PC (280 microg)
      coupled to porcine thyroglobulin (PC-thyr) encapsulated in DL-PLG microspheres,
      free PC-thyr, or blank microspheres. A significant rise in anti-PC immunoglobulin
      A (IgA) titers, as measured by an enzyme-linked immunosorbent assay, was observed
      in the intestinal secretions after immunization with PC-loaded microspheres,
      compared to the titers of mice immunized with free PC-thyr or blank microspheres.
      This antibody response peaked 14 days after the last boost and correlated with a
      highly significant resistance to oral challenge by S. typhimurium C5 (P < 10(
      3)). Control mice were primed intraperitoneally on day 1 with 15 microg of PC in
      complete Freund's adjuvant and boosted on days 10, 14, and 20 with the same dose
      without adjuvant but via the same route. In these mice, the levels of anti-PC IgA
      in intestinal secretions were equivalent to those of the mice intragastrically
      immunized with PC-loaded microspheres, but protection was significantly weaker,
      suggesting that either the IgAs were not functional or that other immune
      mechanisms are important in protection. Taken together, our results highlight the
      potential of antigen encapsulation in DL-PLG microspheres for eliciting
      protective immunity against invasive intestinal bacterial diseases and suggest
      that a similar strategy could be used against diseases caused by other PC-bearing
      microorganisms.

PMID- 9038288
TI  - Specific binding of soluble peptidoglycan and muramyldipeptide to CD14 on human
      monocytes.
AB  - Previously, we were able to show that soluble peptidoglycan (sPG)-induced
      monokine production in human peripheral monocytes is inhibited by anti-CD14
      monoclonal antibodies and by lipid A partial structures. This suggested but did
      not prove that monocytic surface protein CD14 is involved in the activation of
      human monocytes not only by cell wall components of gram-negative bacteria such
      as lipopolysaccharide (LPS) but also by cell wall components of gram-positive
      bacteria such as sPG. In the present study, we provide experimental evidence that
      CD14 indeed constitutes a binding site for sPG recognition and activation of
      human monocytes. The results show that fluorescein isothiocyanate-sPG (FITC-sPG)
      binds to human monocytes in a saturable, dose-dependent, and specific manner. For
      maximal binding, 2 to 3 microg of FITC-sPG per ml was sufficient, and this
      binding is completed within 90 min; about 40% of the binding is completed within
      the first 3 min. The FITC-sPG binding is considered specific because unlabeled
      sPG and also muramyldipeptide (MDP), the minimal bioactive structure of sPG,
      inhibit the binding of sPG to monocytes in a dose-dependent manner. This specific
      binding was also inhibited by an anti-CD14 monoclonal antibody, LPS, and lipid A
      partial structure compound 406. Direct evidence for an interaction of sPG with
      CD14 is provided by experiments involving native polyacrylamide gel
      electrophoresis that showed a shift of the electrophoretic mobility of CD14 by
      LPS as well as by sPG. These results allow the conclusion that sPG binds directly
      to CD14, that MDP represents the active substructure of sPG, and that CD14 may be
      a lectin-like receptor which plays a key role in cellular stimulation by
      bioactive components of not only gram-negative but also gram-positive bacteria.

PMID- 9038289
TI  - Presence of high levels of leukocyte-associated interleukin-8 upon cell
      activation and in patients with sepsis syndrome.
AB  - In inflammatory and infectious diseases, the presence of circulating cytokines in
      plasma strongly suggests, following their exacerbated production, that saturation
      of specific binding sites has occurred or that an equilibrium between receptor
      bound and free cytokines has been reached. In this report, we demonstrate that in
      addition to circulating interleukin-8 (IL-8), high levels of cell-associated IL-8
      were detected in blood samples from patients with sepsis syndrome. The following
      analysis will reveal that in addition to erythrocytes, which have been dubbed a
      "sink" for IL-8, peripheral blood mononuclear cells (PBMC) and polymorphonuclear
      cells (PMN) contributed to the detection of cell-associated IL-8. On a per cell
      basis, 2,000 to 7,000 times the amount of IL-8 was found associated with PMN than
      with erythrocytes. In addition, circulating cells may well be the source of the
      leukocyte-associated form of IL-8. Similarly, in vitro experiments, such as whole
      blood stimulation assays or the addition of exogenous IL-8 in blood samples,
      demonstrated that a large proportion of the IL-8 was associated with leukocytes.
      This suggests that the trapping of free cytokines onto the cell surface and the
      internalization of the IL-8 bound to its receptor, occurring both in vitro and in
      vivo, allows the detection of this cell-associated form. This analysis of cell
      associated cytokines was extended to IL-1ra, another component of the
      inflammatory response, which, in contrast to IL-8, has been demonstrated to exist
      as an intracellular form. Indeed, cell-associated IL-1ra was also detected in
      septic patients. The measurement of cell-associated proinflammatory and anti
      inflammatory cytokines in patients is clearly a more reliable reflection of their
      production than is the simple measurement in plasma and may provide useful
      indication to further understand the inflammatory process.

PMID- 9038290
TI  - Quantification of the relative contribution of major histocompatibility complex
      (MHC) and non-MHC genes to human immune responses to foreign antigens.
AB  - Understanding the extent to which genetic factors influence the immune response
      is important in the development of subunit vaccines. Associations with HLA gene
      polymorphisms appear insufficient to explain the range of variation in immune
      responses to vaccines and to infections by major pathogens. In this study of
      Gambian twins we report that regulation of the immune response to a variety of
      antigens from Plasmodium falciparum and Mycobacterium tuberculosis is controlled
      by factors which are encoded by genes that lie both within and outside the major
      histocompatibility complex (MHC). We define the relative contribution of these
      genes, which varies for different antigens. The cumulative genetic contribution
      of non-MHC genes to the total phenotypic variance exceeds that of the MHC-encoded
      genes.

PMID- 9038291
TI  - Intrathecal production of interleukin-12 and gamma interferon in patients with
      bacterial meningitis.
AB  - To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in
      children with bacterial meningitis, bioactive IL-12 (p70) and the inactive
      subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF)
      from 35 children with bacterial meningitis and 10 control subjects. The
      production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF
      alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40
      as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was
      hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with
      IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL
      6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10,
      those of IFN-gamma were significantly higher in patients with pneumococcal
      meningitis than in children with meningitis caused by Haemophilus influenzae and
      Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in
      the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may
      contribute to the natural immunity against microorganisms in the CSF compartment
      during the acute phase of bacterial meningitis.

PMID- 9038292
TI  - Reactivity with a specific epitope of outer surface protein A predicts protection
      from infection with the Lyme disease spirochete, Borrelia burgdorferi.
AB  - The response to recombinant vaccines for Lyme disease was studied to determine
      serum antibody levels effective in protecting against tick-transmitted infection.
      Data presented here demonstrate a significant correlation between antibody to an
      epitope on outer surface protein A (OspA) and protection against infection with
      Borrelia burgdorferi in canines and mice. A competitive enzyme-linked
      immunosorbent assay was developed to measure antibody to a site on OspA, defined
      by monoclonal antibody LA-2. Comparison of LA-2 titers against infection of
      canines and mice following vaccination and challenge established a predicted
      value for LA-2 titers. The statistical relationship between serum antibody levels
      and protection was calculated by logistic regression analysis. The statistical
      model predicted that an LA-2 titer of 0.32 microg equivalents (eq) per ml
      correlated to an 80% predicted probability of protection for both mice and dogs.
      This value was used to classify mice and dogs as to their protected status at the
      time of tick exposure. The LA-2 cutoff titer (0.32 microg eq/ml) correctly
      classified all dogs (n = 13) and mice (n = 44) that failed to become infected. By
      contrast, 20 of 22 dogs and 28 of 31 mice with titers of less than 0.32 microg
      eq/ml became infected. On the basis of these results, we conclude that an LA-2
      titer is a reliable indicator of immune status for estimating immune protection
      following use of OspA-based vaccines for B. burgdorferi sensu stricto.

PMID- 9038293
TI  - Detection of the intercellular adhesion gene cluster (ica) and phase variation in
      Staphylococcus epidermidis blood culture strains and mucosal isolates.
AB  - Staphylococcus epidermidis is a common cause of catheter-associated infections
      and septicemia in immunocompromised patients. To answer the question whether S.
      epidermidis skin isolates differ from isolates causing septicemic diseases, 51
      strains obtained from blood cultures, 1 strain from shunt-associated meningitis,
      and 36 saprophytic isolates were characterized. The study demonstrates that most
      of the blood culture strains formed a multilayered biofilm on plastic material,
      whereas skin and mucosal isolates did not. Moreover, biofilm-producing strains
      were found to generate large bacterial autoaggregates in liquid culture.
      Autoaggregation and biofilm formation on polymer surfaces was associated with the
      presence of a DNA sequence encoding an intercellular adhesion gene cluster (ica)
      that mediates the production of a polysaccharide intercellular adhesin. The
      presence of the intercellular adhesion genes in blood culture isolates was also
      found to be correlated with the exhibition of black colonies on Congo red agar,
      whereas the adhesin-negative strains formed red colonies. Upon subcultivation on
      Congo red agar, the black colony forms of the blood culture strains exhibited red
      colony variants which were biofilm and autoaggregation negative and occurred at a
      frequency of 10(-5). The DNA analysis of these S. epidermidis variants by pulsed
      field gel electrophoresis and Southern hybridization with an ica-specific gene
      probe revealed no detectable difference between the black and red colony types.
      Moreover, after repeated passage, the phenotype of the parent strain could be
      restored. Therefore, these colony forms were regarded as phase variants. This
      phenotypic change was observed exclusively in adhesin-positive clinical isolates
      and not in adhesin-negative saprophytic strains of S. epidermidis.

PMID- 9038294
TI  - Vitronectin-binding staphylococci enhance surface-associated complement
      activation.
AB  - Coagulase-negative staphylococci are well recognized in medical device-associated
      infections. Complement activation is known to occur at the biomaterial surface,
      resulting in unspecific inflammation around the biomaterial. The human serum
      protein vitronectin (Vn), a potent inhibitor of complement activation by
      formation of an inactive terminal complement complex, adsorbs to biomaterial
      surfaces in contact with blood. In this report, we discuss the possibility that
      surface-immobilized Vn inhibits complement activation and the effect of Vn
      binding staphylococci on complement activation on surfaces precoated with Vn. The
      extent of complement activation was measured with a rabbit anti-human C3c
      antibody and a mouse anti-human C9 antibody, raised against the neoepitope of C9.
      Our data show that Vn immobilized on a biomaterial surface retains its ability to
      inhibit complement activation. The additive complement activation-inhibitory
      effect of Vn on a heparinized surface is very small. In the presence of Vn
      binding strain, Staphylococcus hemolyticus SM131, complement activation on a
      surface precoated with Vn occurred as it did in the absence of Vn precoating. For
      S. epidermidis 3380, which does not express binding of Vn, complement activation
      on a Vn-precoated surface was significantly decreased. The results could be
      repeated on heparinized surfaces. These data suggest that Vn adsorbed to a
      biomaterial surface may serve to protect against surface-associated complement
      activation. Furthermore, Vn-binding staphylococcal cells may enhance surface
      associated complement activation by blocking the inhibitory effect of preadsorbed
      Vn.

PMID- 9038295
TI  - Variables affecting production of monocyte chemotactic factor 1 from human
      leukocytes stimulated with Cryptococcus neoformans.
AB  - The chemokine monocyte chemoattractant protein 1 (MCP-1) is produced
      predominantly by mononuclear phagocytes and stimulates recruitment into infected
      tissues of blood monocytes and T cells. These cell types are thought to be
      critical to host defenses against infections due to Cryptococcus neoformans, a
      major cause of disease in persons with AIDS and other disorders of cell-mediated
      immunity. Accordingly, in the present study, we examined the conditions under
      which human monocytes and bronchoalveolar macrophages (BAM) are stimulated by C.
      neoformans to produce MCP-1. C. neoformans was a potent inducer of MCP-1 release
      from monocytes, with levels of chemokine secreted similar to that seen following
      stimulation with lipopolysaccharide (LPS). BAM, in contrast, were stimulated by
      LPS, but not by C. neoformans, to secrete MCP-1. A peak in MCP-1 mRNA was seen 8
      h following cryptococcal stimulation of monocytes. Nine strains of C. neoformans
      stimulated monocytes to release MCP-1, and there was only modest variation
      between strains. However, when an individual strain was used, the capacity of C.
      neoformans to stimulate monocyte MCP-1 release did vary, depending upon the
      conditions used to grow the fungal stimuli. Finally, C. neoformans stimulated
      comparable quantities of MCP-1 release in monocytes from donors with and without
      human immunodeficiency virus infection. These data establish C. neoformans as a
      potent stimulator of MCP-1 in monocytes, but not in BAM. The failure of C.
      neoformans to stimulate MCP-1 in BAM, if occurring in vivo, could result in a
      diminished cell-mediated inflammatory response following inhalation of airborne
      fungi.

PMID- 9038296
TI  - Oral immunization with the saliva-binding region of Streptococcus mutans AgI/II
      genetically coupled to the cholera toxin B subunit elicits T-helper-cell
      responses in gut-associated lymphoid tissues.
AB  - Mice immunized intragastrically (i.g.) with a genetically constructed chimeric
      protein consisting of the saliva-binding region (SBR) of Streptococcus mutans
      AgI/II coupled to cholera toxin (CT) A2 and B subunits (CTA2/B) develop serum
      immunoglobulin G (IgG) and mucosal IgA antibody responses against AgI/II that are
      enhanced by the coadministration of CT as an adjuvant. To investigate the
      development of antigen-specific T cells in the gut-associated lymphoid tissues,
      mice were immunized i.g. with SBR, SBR-CTA2/B, or SBR-CTA2/B plus CT. AgI/II
      specific T cells in Peyer's patches (PP), mesenteric lymph nodes (MLN), and
      spleen were assayed by lymphoproliferation and flow cytometry for the expression
      of T-cell surface markers, and cytokine mRNA expression was evaluated by reverse
      transcription-PCR. T-cell responses were consistent with antibody responses but
      were detectable after the first immunization. Proliferative responses of PP and
      MLN cells upon stimulation with AgI/II in vitro were low and delayed in mice
      given SBR alone, and these cells displayed a mixed type 1 and 2 (or Th0) pattern
      of cytokine expression. Immunization with SBR-CTA2/B resulted in greater AgI/II
      specific proliferative responses in PP cells and an increase in the proportion of
      CD4+ T cells. Coadministration of CT with SBR-CTA2/B led to greater proliferative
      responses especially in the MLN cells, which then showed an increase in CD4+
      cells. Immunization with SBR-CTA2/B (with or without CT) skewed the cytokine
      expression pattern in PP and MLN cells toward Th2. The results indicate that T
      helper cells were induced in gut-associated lymphoid tissues by i.g. immunization
      with SBR-CTA2/B, concomitantly with and prior to the appearance of circulating
      and mucosal antibodies.

PMID- 9038298
TI  - Effect of Yersinia pestis YopM on experimental plague.
AB  - YopM of Yersinia pestis has previously been shown to be necessary for full
      virulence in mice and to be able to bind human alpha-thrombin. This activity
      prompted the hypothesis that YopM, functioning extracellularly during plague,
      might be accessible to neutralization by antibody and hence might be a protective
      antigen. This study tested this hypothesis and found that YopM was not
      protective, either by passive or active immunization, in inbred or outbred mice.
      These findings showed that either YopM-specific antibody does not have access to
      YopM during experimental plague or the function of extracellular YopM is not
      neutralizable by antibody. Exogenously supplied YopM partially restored virulence
      to a YopM- strain of Y. pestis while having no effect on lethality of Listeria
      monocytogenes. These findings indicate that YopM does not significantly alter
      host defenses important for resistance against heterologous infection (Listeria
      monocytogenes) but raise the possibility that YopM has a minor extracellular
      function specific to homologous infection (Y. pestis).

PMID- 9038297
TI  - Identification of the N-acetylneuraminyllactose-specific laminin-binding protein
      of Helicobacter pylori.
AB  - The interaction of the gastroduodenal pathogen Helicobacter pylori with the
      glycoprotein laminin was investigated. Binding of 125I-radiolabelled laminin in a
      liquid-phase assay by both hemagglutinating and poorly hemagglutinating strains
      was rapid, saturable, specific, partially reversible, of high affinity, and
      insensitive to pH. Inhibition of laminin binding by fetuin, but not asialofetuin,
      and reduced bacterial binding to periodate- or sialidase-treated laminin
      indicated that glycosylation, particularly sialylation, was important for laminin
      binding by H. pylori. Inhibition experiments with monosaccharides, disaccharides,
      and trisaccharides showed that the strains bound to a region spanning a
      trisaccharide. In particular, inhibition and displacement studies showed that
      binding to the trisaccharide N-acetylneuraminyl-alpha(2-3)-lactose [NeuAc(2
      3)Lac] was preferential to that to the NeuAc(2-6)Lac isomer. Complete inhibition
      of laminin binding by both hemagglutinating and poorly hemagglutinating strains
      was achieved only when isolated lipopolysaccharide (LPS) was used as an inhibitor
      in combination with heat or protease treatment of H. pylori cells, thereby
      confirming the involvement of both LPS and a protein adhesin in laminin binding.
      Further inhibition experiments indicated that the protein receptor, rather than
      LPS, on H. pylori bound NeuAc(2-3)Lac. By using a Western blotting procedure, a
      25-kDa outer membrane protein was identified as mediating laminin binding by both
      hemagglutinating and poorly hemagglutinating H. pylori strains. The specificity
      of binding was confirmed by complete inhibition of laminin binding by the 25-kDa
      protein with NeuAc(2-3)Lac. The data collectively suggest that a 25-kDa outer
      membrane protein acts in a lectin-like manner with LPS to mediate attachment of
      H. pylori to laminin.

PMID- 9038299
TI  - Binding of Cryptococcus neoformans to heterologously expressed human complement
      receptors.
AB  - Previously, we demonstrated that monoclonal antibodies (MAb) directed against any
      of the three defined complement receptors (CR) for the third component of
      complement (CR1, CR3, and CR4) profoundly inhibited the binding of serum
      opsonized Cryptococcus neoformans to monocyte-derived macrophages. These studies
      suggested either that a synergistic interaction between multiple CR was required
      for optimal binding of C. neoformans or that the MAb were exerting nonspecific
      effects (such as receptor coassociation). In the present studies, we took a novel
      approach to dissecting out the contributions of individual receptors to binding
      of a microbial pathogen. Chinese hamster ovary (CHO) cells stably transfected
      with human CR1, CR3, or CR4 were challenged with serum-opsonized C. neoformans.
      We found that CHO cells transfected with any of the three receptors bound C.
      neoformans, with the avidity of binding to CR3 being the greatest followed in
      decreasing order by CR1 and CR4. Following binding of C. neoformans to
      transfected CHO cells, most organisms remained surface attached only, although
      for each receptor a significant percentage (18.5 to 27.3%) of C. neoformans was
      internalized. Both C. neoformans and sheep erythrocytes that were selectively
      opsonized with the fragments of the third component of complement, C3b and iC3b,
      were bound preferentially by CHO cells transfected with CR1 and CR3,
      respectively. These data establish CR1, CR3, and CR4 as receptors independently
      capable of binding C. neoformans opsonized with fragments of C3. Moreover, our
      study demonstrates the usefulness of transfected cell lines as a powerful tool
      for identifying the contribution of individual receptors to the binding of a
      microbial pathogen.

PMID- 9038301
TI  - Decoration of lipopolysaccharide with phosphorylcholine: a phase-variable
      characteristic of Haemophilus influenzae.
AB  - Choline, although not a nutritional requirement for Haemophilus influenzae, is
      taken up from the growth medium and incorporated into its lipopolysaccharide
      (LPS). Incorporated choline is in the form of phosphorylcholine (ChoP) based on
      the reactivity with the monoclonal antibody with specificity for this structure,
      TEPC-15. Incorporation of [3H]choline from the growth medium and expression of
      the TEPC-15 epitope undergo high-frequency phase variation, characteristic of
      other LPS structures in this species. The expression and phase variation of ChoP
      require a previously identified locus involved in LPS biosynthesis, lic1. The
      first gene in lic1, licA, contains a translational switch based on variation in
      the number of intragenic tandem repeats of the sequence 5'-CAAT-3'. The full
      length LicA polypeptide resembles choline kinases of eucaryotes, suggesting that
      the pathway for choline incorporation into the H. influenzae glycolipid has
      similarities to the pathway for choline incorporation in eucaryotic lipid
      synthesis. The display of ChoP, a host-like structure, renders the organism more
      rather than less susceptible to the bactericidal activity of human serum. The
      increased serum sensitivity of variants with ChoP correlates with higher serum
      immunoglobulin G titers to LPS containing this structure. ChoP appears to be a
      cell surface feature common to a number of pathogens of the human respiratory
      tract, including Streptococcus pneumoniae and mycoplasmas. In the case of H.
      influenzae, its primary contribution to pathogenesis does not appear to be
      antigenic variation to evade host humoral clearance mechanisms.

PMID- 9038300
TI  - Interleukin-12 modulates the protective immune response in SCID mice infected
      with Histoplasma capsulatum.
AB  - Infection with Histoplasma capsulatum results in a subclinical infection in
      immunocompetent hosts due to an effective cellular immune response. By contrast,
      immunodeficient individuals can have a severe disseminated and potentially fatal
      disease. In a previous study, it was demonstrated that normal mice infected
      intravenously with H. capsulatum and treated with interleukin-12 (IL-12) at the
      time of infection were protected from a fatal outcome. In this study, we examined
      the immunomodulatory effects of IL-12 on disseminated histoplasmosis in
      immunodeficient SCID mice. SCID mice infected with H. capsulatum and treated with
      IL-12 showed an increase in survival and a reduction in the colony counts of H.
      capsulatum in internal organs at 14 days after infection. The protective effect
      of IL-12 was abrogated if animals were also treated with a neutralizing antibody
      to gamma interferon (IFN-gamma). IL-12 treatment also resulted in an increase in
      mRNA expression and protein production for IFN-gamma, tumor necrosis factor alpha
      (TNF-alpha), and nitric oxide from spleen cells. When IL-12 was combined with
      amphotericin B (AmB) treatment, there was a significant increase in survival
      compared with either modality alone. Moreover, combined treatment resulted in an
      increase in both IFN-gamma and TNF-alpha production, as well as in a substantial
      reduction in H. capsulatum burden at 35 and 90 days postinfection. This study
      demonstrates that IL-12 modulates the protective immune response to
      histoplasmosis in SCID mice and also suggests that IL-12 in combination with AmB
      may be useful as a treatment for H. capsulatum in immunodeficient hosts.

PMID- 9038302
TI  - Cross-reactive cytotoxic T-lymphocyte-mediated lysis of Chlamydia trachomatis-
      and Chlamydia psittaci-infected cells.
AB  - Cells infected with Chlamydia trachomatis are lysed by CD8+ T cells in vitro. The
      ability of C. trachomatis-elicited spleen cells to lyse target cells infected
      with other chlamydial strains was determined by measuring lysis by immune spleen
      cells of targets infected with three strains of C. trachomatis and two strains of
      C. psittaci. C. trachomatis (lymphogranuloma venereum [LGV])-elicited immune
      murine spleen cells lysed target cells infected with other C. trachomatis
      serovars, although with lower sensitivity than they lysed LGV-infected target
      cells. Additionally, target cells infected with C. psittaci were lysed by C.
      trachomatis-elicited immune spleen cells. Notably, C. psittaci-infected cells
      were lysed with greater efficiency than were cells infected with the C.
      trachomatis strain used to elicit the immune spleen cells. The lysis of C.
      psittaci-infected cells was characterized further and could be only partially
      accounted for by CD8+ T-cell-mediated lysis, the remaining lysis being due to an
      antigen-nonspecific component. These results indicate that mechanisms of
      immunologically mediated lysis differ between C. trachomatis- and C. psittaci
      infected cells. This has important implications for the interpretation of results
      obtained with C. psittaci models of infection and immune resolution, particularly
      as they may be extrapolated to C. trachomatis.

PMID- 9038303
TI  - Increase of glycocalyx and altered lectin agglutination profiles of Pasteurella
      haemolytica A1 after incubation in bovine subcutaneous tissue chambers in vivo or
      in ruminant serum in vitro.
AB  - Pasteurella haemolytica serotype A1 (bovine strain OK) was incubated for 2 and 6
      h in bovine subcutaneous tissue chambers in vivo, and ovine strain 82-25 and
      bovine strain L011 were incubated in vitro for 2 h in heat-inactivated ovine or
      bovine serum from which gamma globulin had been depleted by protein G affinity
      chromatography to assess changes in morphology and lectin agglutination profiles
      (strains 82-25 and L101 only). Cells, removed from chambers after 2 h, were
      covered with an extensive, dense glycocalyx extending approximately 0.5 microm
      from the cell surface. In many cells, the glycocalyx was separated from the cell
      surface by a clear, electron-transparent area. Cells, removed at 6 h, were
      covered with a sparse glycocalyx of fine fibers 0.2 to 0.3 microm from the cell
      surface. Strains 82-25 and L101, incubated for 2 h in heat-inactivated ovine or
      bovine serum or in heat-inactivated ovine or bovine serum depleted of gamma
      globulin by protein G affinity chromatography, were also covered with a
      glycocalyx. The glycocalyx did not bind protein A-colloidal gold and therefore
      did not contain aggregates of accumulated antibody. Strains 82-25 and L101 were
      incubated individually for 2 h in 10 mM sodium phosphate buffer (pH 7.2)
      containing 0.14 M NaCl, 0.5 mM CaCl2, and 0.15 mM MgCl2 or with this buffer and
      either 25% heat-inactivated, gamma globulin-depleted ovine serum or 25% heat
      inactivated, gamma globulin-depleted bovine serum. Agglutination profiles were
      then determined with 17 lectins in 10 mM HEPES-buffered saline (pH 8.4) with 0.1
      mM CaCl2 and 0.08% sodium azide. Profiles did not vary with 10 of 17 lectins.
      However, profiles did vary with peanut agglutinin, Phaseolus vulgaris
      leucoagglutinin, Sophora japonica agglutinin, Maackia amurensis lectin II,
      Narcissus pseudonarcissus (daffodil) lectin, Griffonia simplicifolia lectin I,
      and Pisum sativum agglutinin. Altered profiles indicate a change in the bacterial
      cell surface, possibly by adsorption or alteration of surface carbohydrate
      moieties by serum constituents.

PMID- 9038304
TI  - Vitronectin mediates internalization of Neisseria gonorrhoeae by Chinese hamster
      ovary cells.
AB  - Gonococci producing a distinct opacity protein (OpaA in strain MS11) adhere to
      and are efficiently internalized by cultured epithelial cells such as the Chang
      conjunctiva cell line. Both adherence and uptake require interactions between
      OpaA and heparan sulfate proteoglycans on the mammalian cell surface. Chinese
      hamster ovary (CHO) cells also support adherence of gonococci through
      interactions of OpaA with cell surface heparan sulfate proteoglycans. However,
      despite this similarity in the requirements for adherence, CHO cells are not
      capable of internalizing gonococci. In this report, we characterized this
      apparent deficiency and identified a factor in fetal calf serum (FCS) which is
      capable of mediating uptake of gonococci by CHO cells. In the absence of FCS,
      OpaA+ gonococci adhered to but were not internalized by CHO cells, whereas in the
      presence of up to 15% FCS, the bacteria were efficiently internalized by the
      cells. Preincubation of bacteria, but not cells, with FCS also stimulated
      internalization, suggesting that a factor present in FCS was binding to the
      surface of gonococci and subsequently stimulating entry. Using a combination of
      chromatographic purification procedures, we identified the adhesive glycoprotein
      vitronectin as the serum factor which mediates the internalization of gonococci
      by CHO cells. Vitronectin-depleted serum did not support gonococcal entry, and
      this deficiency was restored by the addition of purified vitronectin. Further
      experiments using a set of gonococcal recombinants, each expressing a single
      member of the family of Opa outer membrane proteins, demonstrated that
      vitronectin bound to the surface of OpaA-producing gonococci only and that the
      vitronectin-mediated uptake by the CHO cells was limited to this bacterial
      phenotype. To our knowledge, our data are the first example that vitronectin can
      serve as a molecule that drives bacterial entry into epithelial cells.

PMID- 9038305
TI  - Infection with Trypanosoma cruzi selectively upregulates B7-2 molecules on
      macrophages and enhances their costimulatory activity.
AB  - T-cell-mediated immune responses are essential for protection against infection
      with the protozoan Trypanosoma cruzi. In this study, we investigated the
      influence of infection of murine macrophages with T. cruzi on costimulatory
      signals for T lymphocytes provided by these cells. We demonstrate that bone
      marrow-derived macrophages (BMMph) selectively and strongly upregulate expression
      of B7-2 molecules after infection, while the expression of other costimulatory
      molecules such as B7-1, intercellular adhesion molecule 1, lymphocyte function
      associated antigen 3, and heat-stable antigen is not significantly affected.
      Infection by live trypanosomes was required. As a consequence of the strong B7-2
      upregulation, the infected macrophages are able to induce proliferation of
      splenic CD4+ T cells in the presence of anti-CD3 antibodies with much higher
      efficiency than uninfected macrophages. Costimulation could be inhibited by an
      antibody to B7-2. Furthermore, costimulatory activity for established T-cell
      clones of Th1 and Th2 phenotype was also strongly enhanced in BMMph by infection
      with T. cruzi. Th1 cells stimulated either via anti-CD3 antibodies or via
      specific antigen proliferated with higher efficiency in the presence of infected
      macrophages than in the presence of uninfected cells. BMMph stimulated with gamma
      interferon (IFN-gamma), expressing elevated levels of B7-2 molecules, are also
      able to enhance Th1 cell proliferation, which was highest, using macrophages
      which were infected and in parallel were stimulated with IFN-gamma. Noteworthy,
      for cloned Th2 cells, the mechanism of costimulation differed, because
      costimulation of Th2 cells was not dependent on B7-2 upregulation but was due to
      secretion of interleukin-1alpha. These findings demonstrate that infection of
      macrophages with T. cruzi transforms the macrophage into a potent costimulatory
      cell based on the induction of two different costimulatory activities.

PMID- 9038306
TI  - Porcine polymorphonuclear leukocytes generate extracellular microbicidal activity
      by elastase-mediated activation of secreted proprotegrins.
AB  - Antimicrobial peptides of several structural classes have been found in
      phagocytes and epithelial cells of many animals. The broadly microbicidal
      protegrins (PG1, -2, and -3) were originally isolated as 16 to 18-amino-acid
      peptides from pig neutrophil lysates, but the corresponding cDNA sequences
      encoded much larger precursors that belonged to the cathelicidin family of
      antimicrobial peptides. We explored the storage, secretion, and microbicidal
      activation of protegrins in porcine neutrophils and in a model system consisting
      of recombinant proprotegrin 3 (pPG3) and various serine proteases and their
      inhibitors. Protegrins were stored in neutrophils as inactive proforms that were
      cleaved by neutrophil elastase to mature protegrins during the preparation of
      granule lysate and during phorbol myristate acetate-stimulated granule secretion
      from intact neutrophils. Recombinant pPG3 was efficiently cleaved by trace
      amounts of human neutrophil elastase or equivalent amounts of elastase activity
      from porcine neutrophils, but pPG3 was relatively resistant to porcine pancreatic
      elastase or human neutrophil cathepsin G. The recombinant pPG3 and neutrophil
      proprotegrins lacked microbicidal activity, but the mature protegrins generated
      in the elastase-mediated cleavage reaction were as active against Listeria
      monocytogenes as the chemically synthesized protegrin. The secretion and elastase
      mediated activation of proprotegrins accounted for much of the stable
      microbicidal activity of porcine neutrophil secretions against L. monocytogenes.
      Secreted proprotegrins and trace amounts of elastase constitute a binary
      microbicidal system that is likely to contribute to the antimicrobial activity of
      porcine inflammatory fluids.

PMID- 9038307
TI  - Elimination of resident macrophages from the livers and spleens of immune mice
      impairs acquired resistance against a secondary Listeria monocytogenes infection.
AB  - During a secondary Listeria monocytogenes infection in mice, the bacteria are
      eliminated more rapidly from the liver and spleen than during a primary
      infection. This acquired resistance against a secondary infection is dependent on
      T lymphocytes, which induce enhanced elimination of bacteria via stimulation of
      effector cells such as neutrophils, resident macrophages, exudate macrophages,
      and hepatocytes. The aim of the present study was to determine the role of the
      resident macrophages in acquired resistance against a secondary L. monocytogenes
      infection in mice. Mice which had recovered from a sublethal primary infection
      with 0.1 50% lethal dose (LD50) of L. monocytogenes intravenously (i.v.), i.e.,
      immune mice, received a challenge of 1 LD50 of L. monocytogenes i.v. to induce a
      secondary infection. At 2 days prior to challenge, immune mice were given an i.v.
      injection of liposomes containing dichloromethylene-diphosphonate (L-Cl2MDP) to
      selectively eliminate resident macrophages from the liver and spleen. Control
      immune mice received either phosphate-buffered saline (PBS) or liposomes
      containing PBS (L-PBS). Treatment of mice with L-Cl2MDP effectively eliminated
      resident macrophages from the liver and spleen but did not affect the number of
      granulocytes, monocytes, or lymphocytes in peripheral blood or their migration to
      a site of inflammation. Phagocytosis and killing of L. monocytogenes by
      peritoneal exudate cells elicited with heat-killed L. monocytogenes were similar
      in all groups of immune mice. On day 3 of a secondary infection, the number of L.
      monocytogenes organisms in the livers and spleens of L-Cl2MDP-treated immune mice
      was 4 log10 units higher than in immune mice treated with PBS or L-PBS. The
      concentration of reactive nitrogen intermediates in plasma, a measure of the
      severity of infection, was 70-fold higher for L-Cl2MDP-treated immune mice than
      for PBS- or L-PBS-treated immune mice. Treatment with L-Cl2MDP significantly
      increased the number of inflammatory foci in the liver and spleen, decreased
      their size, and affected their structure. From these results, we conclude that
      resident macrophages are required for the expression of acquired resistance
      against a secondary L. monocytogenes infection in mice.

PMID- 9038308
TI  - Immunization with FimA protects against Streptococcus parasanguis endocarditis in
      rats.
AB  - FimA, a surface-associated protein of Streptococcus parasanguis, is associated
      with initial colonization of damaged heart tissue in an endocarditis model (D.
      Burnette-Curley, V. Wells, H. Viscount, C. Munro, J. Fenno, P. Fives-Taylor, and
      F. Macrina, Infect. Immun. 63:4669-4674, 1995). We have evaluated the efficacy of
      recombinant FimA as a vaccine in the rat model of endocarditis and investigated
      in vitro the mechanism for the protective role of immunization. FimA-immunized
      and nonimmunized control animals were catheterized to induce heart valve damage
      and infected intravenously with 10(7) CFU of wild-type S. parasanguis FW213
      bacteria. The presence of bacteria associated with platelet-fibrin vegetations 24
      h postchallenge was evaluated. Immunized rats were significantly less susceptible
      to endocarditis (2 cases among 34 animals) than the control group (21 cases among
      33 animals) (P < 0.001). Incubation of S. parasanguis FW213 with rabbit anti-FimA
      immune serum decreased the mean percent adherence (0.34% of added cells) to
      platelet-fibrin matrix in vitro compared with that of preimmune normal serum
      (5.04% of added cells; P < 0.001). Adsorption of immune serum with FimA-positive
      S. parasanguis FW213 yielded antiserum that failed to block adherence to the
      platelet-fibrin matrix. We assessed the vaccine potential of FimA as a common
      immunogen able to provide cross-protection in streptococcal endocarditis by
      determining the occurrence and expression of fimA in the viridans group
      streptococci and enterococci. We detected the presence of fimA homologs by
      Southern hybridization and PCR amplification analyses and determined by
      immunoblotting the expression of FimA-like proteins among a variety of
      streptococci and enterococci that frequently cause endocarditis. Eighty-one
      percent (26 of 32) of streptococcal and enterococcal strains isolated from
      bacteremic patients expressed proteins that comigrated with FimA and were
      reactive with polyclonal anti-FimA serum. Streptococcal DNA from strains that
      were positive by Western blot (immunoblot) analysis hybridized to the full-length
      fimA probe. Our studies suggest that FimA immunization results in antibody
      mediated inhibition of bacterial adherence, a critical early event in the
      pathogenesis of endocarditis. Our data demonstrate that a majority of
      streptococcal strains associated with endocarditis have genes that encode FimA
      like proteins. Taken together, these results suggest that FimA is a promising
      candidate for an endocarditis vaccine.

PMID- 9038309
TI  - Scarring trachoma is associated with polymorphism in the tumor necrosis factor
      alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid.
AB  - Tumor necrosis factor alpha (TNF-alpha) may play a central role in the disease
      pathogenesis which occurs as a consequence of chlamydial infection. To
      investigate the importance of TNF-alpha gene promoter polymorphisms and TNF-alpha
      levels in tear fluid in scarring trachoma, a large matched-pair case-control
      study was performed in The Gambia. The -308A allele was present in a higher
      proportion of patients (28.4%) than controls (18.4%), with an increasing
      association for homozygotes (chi2 for trend, P = 0.032; allele frequency, 0.163
      in patients and 0.099 in controls; chi2, P = 0.025). For the -238A allele, the
      association was similar but not significant. The disease association was highly
      significant when the number of either -308A or -238A sites in an individual was
      considered (P = 0.003). TNF-alpha promoter alleles are tightly linked to some HLA
      class I and II alleles, but multivariate analysis confirmed that the disease
      associations were independent of HLA, although a class I allele, A*6802, is also
      associated with disease. TNF-alpha was more frequently detected in tear samples
      from patients (27.6%) than from controls (15.9%), increasingly so for higher
      levels of detectable TNF-alpha (P = 0.015). Among patients, detectable TNF-alpha
      in tears was highly associated with the presence of ocular chlamydial infection
      (P < 0.001). The results indicate that TNF-alpha plays a major role in the tissue
      damage and scarring which occurs as a consequence of Chlamydia trachomatis
      infection.

PMID- 9038310
TI  - Cloning and characterization of the Bacteroides fragilis metalloprotease toxin
      gene.
AB  - Strains of Bacteroides fragilis that produce a ca. 20-kDa heat-labile protein
      toxin (termed B. fragilis toxin [BFT]) have been associated with diarrheal
      disease of animals and humans. BFT alters the morphology of intestinal epithelial
      cells both in vitro and in vivo and stimulates secretion in ligated intestinal
      segments of rats, rabbits, and lambs. Previous genetic and biochemical data
      indicated that BFT was a metalloprotease which hydrolyzed G (monomeric) actin,
      gelatin, and azocoll in vitro. In this paper, the cloning and sequencing of the
      entire B. fragilis toxin gene (bft) from enterotoxigenic B. fragilis (ETBF) 86
      5443-2-2 is reported. The bft gene from this ETBF strain consists of one open
      reading frame of 1,191 nucleotides encoding a predicted 397-residue holotoxin
      with a calculated molecular weight of 44,493. Comparison of the predicted BFT
      protein sequence with the N-terminal amino acid sequence of purified BFT
      indicates that BFT is most probably synthesized by ETBF strains as a
      preproprotein. These data predict that BFT is processed to yield a biologically
      active toxin of 186 residues with a molecular mass of 20.7 kDa which is secreted
      into the culture supernatant. Analysis of the holotoxin sequence predicts a 20
      residue amphipathic region at the carboxy terminus of BFT. Thus, in addition to
      the metalloprotease activity of BFT, the prediction of an amphipathic domain
      suggests that oligomerization of BFT may permit membrane insertion of the toxin
      with creation of a transmembrane pore. Comparison of the sequences available for
      the bft genes from ETBF 86-5443-2-2 and VPI 13784 revealed two regions of reduced
      homology. Hybridization of oligonucleotide probes specific for each bft to
      toxigenic B.fragilis strains revealed that 51 and 49% of toxigenic strains
      contained the 86-5433-2-2 and VPI 13784 bft genes, respectively. No toxigenic
      strain hybridized with both probes. We propose that these two subtypes of bft be
      termed bft-1 (VPI 13784) and bft-2 (86-5433-2-2).

PMID- 9038311
TI  - Deletion analysis of the Clostridium perfringens enterotoxin.
AB  - To further our knowledge of the structure-function relationship and mechanism of
      action of the Clostridium perfringens enterotoxin (CPE), a series of recombinant
      CPE (rCPE) species containing N- and C-terminal CPE deletion fragments was
      constructed by recombinant DNA approaches. Each rCPE species was characterized
      for its ability to complete the first four early steps in the action of CPE,
      putatively ordered as specific binding, a postbinding physical change to bound
      CPE, large-complex formation, and induction of alterations in small-molecule
      membrane permeability. These studies demonstrated that (i) at least 44 amino
      acids can be removed from the N terminus of CPE without loss of cytotoxicity,
      (ii) removal of the first 53 amino acids from the N terminus of CPE produces a
      fragment that appears to be noncytotoxic because it cannot undergo the post
      binding physical change step in CPE action, (iii) removal of as few as five amino
      acids from the C terminus of CPE produces a noncytotoxic fragment lacking
      receptor binding activity, and (iv) a fragment lacking the first 44 N-terminal
      amino acids of native CPE formed twice as much large complex and was twice as
      cytotoxic as native CPE. From these structure-function results, it appears that
      the minimum-size cytotoxic CPE fragment comprises approximately residues 45 to
      319 of native CPE. Results from these deletion fragment studies have also
      contributed to our understanding of CPE action by (i) independently supporting
      previous suggestions that binding, the postbinding physical change step, and
      large-complex formation represent important steps in CPE cytotoxicity and (ii)
      providing independent evidence confirming the putative sequential order of these
      early events in CPE action.

PMID- 9038312
TI  - Purification and in vitro activities of rabbit platelet microbicidal proteins.
AB  - Recent in vitro studies have demonstrated that rabbit platelets release a small,
      cationic antimicrobial protein in response to thrombin stimulation under
      physiological conditions (M. R. Yeaman, S. M. Puentes, D. C. Norman, and A. S.
      Bayer, Infect. Immun. 60:1202-1209, 1992). This observation prompted our present
      investigation, focused on determining the array of antimicrobial proteins
      contained within rabbit platelets and their in vitro activity against common
      bloodstream pathogens. A group of small (6.0- to 9.0-kDa), cationic proteins with
      in vitro antimicrobial activity was purified from whole and thrombin-stimulated
      rabbit platelets by gel filtration and reversed-phase high-performance liquid
      chromatography. Purified proteins in micromolar concentrations (10 to 40
      microg/ml) exerted in vitro microbiostatic and/or microbicidal activities against
      Staphylococcus aureus, Escherichia coli, and Candida albicans in a dose-dependent
      manner. The antimicrobial activities of proteins purified from rabbit platelet
      acid extracts were generally inversely related to pH, with maximal activity
      observed at pH 5.5. In contrast, the predominant protein isolated from thrombin
      stimulated rabbit platelets, though biochemically and microbiologically similar
      to proteins extracted by acid, exhibited antimicrobial activities which were
      modestly enhanced at pH 7.2 compared with pH 5.5. Amino acid compositional
      analyses in combination with molecular mass determinations suggest that the
      majority of these proteins are distinct molecules not derived from a single
      common precursor. Collectively, these data indicate that rabbit platelets contain
      proteins which exert potent in vitro antimicrobial activity against bacterial and
      fungal pathogens which commonly invade the bloodstream. Moreover, several of
      these proteins were released from platelets stimulated with thrombin under
      physiological conditions and exerted potent antimicrobial activities in
      physiological pH ranges. These observations support the hypothesis that platelets
      serve an important role in host defense against infection, via localized release
      of antimicrobial proteins in response to stimuli associated with tissue injury or
      microbial colonization.

PMID- 9038313
TI  - Genital tract infection with Chlamydia trachomatis fails to induce protective
      immunity in gamma interferon receptor-deficient mice despite a strong local
      immunoglobulin A response.
AB  - CD4+ T cells have been found to play a critical role in immune protection against
      Chlamydia trachomatis infection. Since both humoral and cell-mediated
      antichlamydial immunity have been implicated in host protection, the crucial
      effector functions provided by the CD4+ T cells may rely on Th1 or Th2 functions
      or both. In the present study, we evaluated the development of natural immunity
      following vaginal infection with C. trachomatis serovar D in female gamma
      interferon receptor-deficient (IFN-gammaR-/-) mice with a disrupted Th1 effector
      system. We found that in comparison with wild-type mice, the IFN-gammaR-/- mice
      exhibited a severe ascending primary infection of prolonged duration which
      stimulated almost 10-fold-stronger specific local immunoglobulin A (IgA) and IgG
      responses in the genital tract. Following resolution of the primary infection and
      despite the augmented antibody responses to chlamydiae, the IFN-gammaR-/- mice
      were completely unprotected against reinfection, suggesting that local antibodies
      play a subordinate role in host protection against chlamydial infection.
      Immunohistochemical analysis of frozen sections of the genital tract revealed
      many CD4+ T cells in the IFN-gammaR-/- mice, with a dominance of interleukin 4
      containing cells in mice following resolution of the secondary infection.
      However, in contrast to the findings with wild-type mice, the typical clusters of
      CD4+ T cells were not found in the IFN-gammaR-/- mice. Few and similarly
      distributed CD8+ T cells were observed in IFN-gammaR-/- and wild-type mice.
      Whereas chlamydia-infected macrophages from wild-type mice had no inclusion
      bodies (IB) and produced significant amounts of nitric oxide (NO) in the presence
      of IFN-gamma, macrophages from IFN-gammaR-/- mice contained many IB but no NO.
      These results indicate that CD4+ Th1 cells and IFN-gamma, rather than local
      antibodies, are critical elements in host immune protection stimulated by a
      natural ascending C. trachomatis infection in the female genital tract.

PMID- 9038314
TI  - Preclinical evaluation of group B Neisseria meningitidis and Escherichia coli K92
      capsular polysaccharide-protein conjugate vaccines in juvenile rhesus monkeys.
AB  - We reported the first use of group B meningococcal conjugate vaccines in a
      nonhuman primate model (S. J. N. Devi, C. E. Frasch, W. Zollinger, and P. J.
      Snoy, p. 427-429, in J. S. Evans, S. E. Yost, M. C. J. Maiden, and I. M. Feavers,
      ed., Proceedings of the Ninth International Pathogenic Neisseria Conference,
      1994). Three different group B Neisseria meningitidis capsular polysaccharide (B
      PS)-protein conjugate vaccines and an Escherichia coli K92 capsular
      polysaccharide-tetanus toxoid (K92-TT) conjugate vaccine are here evaluated for
      safety and relative immunogenicities in juvenile rhesus monkeys with or without
      adjuvants. Monkeys were immunized intramuscularly with either B PS-cross-reactive
      material 197 conjugate, B PS-outer membrane vesicle (B-OMV) conjugate, or N
      propionylated B PS-outer membrane protein 3 (N-pr. B-OMP3) conjugate vaccine with
      or without adjuvants at weeks 0, 6, and 14. A control group of monkeys received
      one injection of the purified B PS alone, and another group received three
      injections of B PS noncovalently complexed with OMV. Antibody responses as
      measured by enzyme-linked immunosorbent assay varied among individual monkeys.
      All vaccines except B PS and the K92-TT conjugate elicited a twofold or greater
      increase in total B PS antibodies after one immunization. All vaccines, including
      the K92-TT conjugate, elicited a rise in geometric mean B PS antibody levels of
      ninefold or more over the preimmune levels following the third immunization.
      Antibodies elicited by N-pr. B-OMP3 and B-OMV conjugates were directed to the N
      propionylated or to the spacer-containing B PS antigens as well as to the native
      B PS complexed with methylated human serum albumin. None of the vaccines caused
      discernible safety-related symptoms.

PMID- 9038315
TI  - Bactericidal antibody responses of juvenile rhesus monkeys immunized with group B
      Neisseria meningitidis capsular polysaccharide-protein conjugate vaccines.
AB  - Reports on the bactericidal activities of antibodies to group B Neisseria
      meningitidis capsular polysaccharide (B PS) are conflicting. Using three
      different complement sources, we analyzed the bactericidal activities of sera of
      juvenile rhesus monkeys immunized with five conjugate vaccines of B PS
      synthesized by different schemes, an Escherichia coli K92 conjugate, and a
      noncovalent complex of B PS with group B meningococcal outer membrane vesicles
      (B+OMV) (S. J. N. Devi, W. D. Zollinger, P. J. Snoy, J. Y. Tai, P. Costantini, F.
      Norelli, R. Rappuoli, and C. E. Frasch, Infect. Immun. 65:1045-1052, 1997). With
      rabbit complement, nearly all preimmune sera showed relatively high bactericidal
      titers, and all vaccines, except the K92 conjugate, induced a fourfold or greater
      increase in bactericidal titers in most of the monkeys vaccinated. In contrast,
      with human complement, most prevaccination sera showed no bactericidal activity
      and in most of the vaccine groups, little or no increase in bactericidal titer
      was observed. However, the covalent conjugation of P BS and OMV (B-OMV)
      administered with and without the Ribi adjuvant induced relatively high
      bactericidal titers which persisted up to 30 weeks. An analysis of the
      specificities of bactericidal antibodies revealed that absorption with E. coli K1
      cells did not change the bactericidal titer with human complement but reduced the
      titers observed with the rabbit and monkey complements. A significant increase in
      anti-lipopolysaccharide (LPS) antibodies was elicited by the B-OMV conjugates,
      and nearly all of the bactericidal activity with human complement could be
      inhibited with the purified group B meningococcal L3,7,8 LPS. B-OMV covalently
      coupled via adipic acid dihydrazide elicited significantly elevated levels (P <
      or = 0.02) of anti-OMV antibodies compared to those of the noncovalently
      complexed B+OMV. An initial small-scale evaluation of B PS conjugates in adult
      human males appears feasible, with careful monitoring, to settle the inconsistent
      reports of the importance of source of complement in eliciting bacteriolysis.
      Subsequent analysis of resultant human antibodies for bacteriolysis,
      opsonophagocytosis, and protective efficacy in animal models may be the first
      step toward answering safety- and efficacy-related concerns about B PS conjugate
      vaccines.

PMID- 9038316
TI  - Human T-cell clones to the 70-kilodalton heat shock protein of Mycobacterium
      leprae define mycobacterium-specific epitopes rather than shared epitopes.
AB  - The mycobacterial 70-kDa heat shock protein (Hsp70) is a dominant antigen during
      the human T-cell response to mycobacterial infection despite the conserved
      sequence with the human homolog. To determine whether this response is pathogen
      specific, CD4+ T-cell clones were isolated from Mycobacterium leprae Hsp70
      reactive individuals. The cytokine profile of the clones was mixed, with all of
      the clones releasing interferon gamma and half releasing interleukin-4 on
      stimulation, while six demonstrated cytolytic activity. Five clones reacted with
      the N-terminal half of the molecule, and the epitopes identified were
      mycobacterium specific. Residues 241 to 260 were identified by three clones, one
      of which was restricted by HLA-DR7 (DR7), while a DR1-restricted clone identified
      residues 71 to 90 and residues 261 to 280 were recognized in the context of DR3.
      The remaining five T-cell clones reacted with the C-terminal half of the
      molecule, and the precise position of these epitopes was mapped with 12-mer
      peptides overlapping by 11 residues. Two of these clones identified overlapping
      epitopes from residues 411 to 425 and 412 to 428, the latter restricted by DR3.
      Further epitopes were mapped to residues 298 to 313 restricted by DRw53, residues
      388 to 406 restricted by DRw52 or DQ2, and residues 471 to 486 restricted by DR1.
      The sequences of three epitopes, residues 411 to 425, 412 to 428, and 471 to 486,
      showed significant identity with the equivalent regions of the prototype human
      Hsp70. However, when amino acid substitutions that made the sequence more like
      the human sequence were introduced, the changes were tolerated poorly as measured
      by proliferation, cytokine production, and cytotoxic potential. Therefore, T-cell
      recognition of the M. leprae Hsp70 antigen occurs in the context of multiple HLA
      DR phenotypes and is exquisitely species specific.

PMID- 9038317
TI  - Augmentation of oxidant injury to human pulmonary epithelial cells by the
      Pseudomonas aeruginosa siderophore pyochelin.
AB  - Pseudomonas aeruginosa causes acute and chronic infections of the human lung,
      with resultant tissue injury. We have previously shown that iron bound to
      pyochelin, a siderophore secreted by the organism to acquire iron, is an
      efficient catalyst for hydroxyl radical (HO.) formation and augments injury to
      pulmonary artery endothelial cells resulting from their exposure to superoxide
      (O2.) and/or H2O2. Sources for O2-. and H2O2 included phorbol myristate acetate
      (PMA)-stimulated neutrophils and pyocyanin. Pyocyanin, another P. aeruginosa
      secretory product, undergoes cell-mediated redox, thereby forming O2-. and H2O2.
      In P. aeruginosa lung infections, damage to airway epithelial cells is probably
      more extensive than that to endothelial cells. Therefore, we examined whether
      ferripyochelin also augments oxidant-mediated damage to airway epithelial cells.
      A549 cells, a human type II alveolar epithelial cell line, was exposed to H2O2,
      PMA-stimulated neutrophils, or pyocyanin, and injury was determined by release of
      51Cr from prelabeled cells. Ferripyochelin significantly increased (> 10-fold)
      oxidant-mediated cell injury regardless of whether H2O2, neutrophils, or
      pyocyanin was employed. Apo-pyochelin was not effective, and ferripyochelin was
      not toxic by itself at the concentrations employed. Spin trapping with alpha-(4
      pyrridyl-1-oxide)-N-t-butyl-nitrone-ethanol confirmed the generation of HO., and
      injury was decreased by a variety of antioxidants, including superoxide
      dismutase, catalase, and dimethylthiourea. These data are consistent with the
      hypothesis that the presence of ferripyochelin at sites of P. aeruginosa lung
      infection could contribute to tissue injury through its ability to promote HO.
      mediated damage to airway epithelial cells.

PMID- 9038319
TI  - Characterization of hemin binding activity of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a causative agent of bacterial pneumonia, otitis
      media, meningitis, and bacteremia. It causes considerable morbidity and mortality
      throughout the world, especially among children, the elderly, and
      immunocompromised individuals. We have demonstrated previously that the growth of
      S. pneumoniae is limited under iron-depleted conditions and can be restored by
      the addition of either hemin or hemoglobin. In the present study, we showed that
      S. pneumoniae had the ability to bind hemin and that the level of hemin binding
      activity was not affected by supplementation of the growth medium with iron.
      Approximately 70 to 80% of the hemin binding activity was mediated by proteinase
      resistant components, and the remainder was mediated by proteins. Hemin binding
      proteins were located in both soluble extract and envelope fractions of
      pneumococcal cells. By batch affinity chromatography, a major hemin binding
      polypeptide with an apparent molecular mass of 43 kDa was identified in the cell
      lysate of S. pneumoniae. Polyclonal antibodies against this polypeptide were
      raised. By immunoblot analysis, this hemin binding polypeptide was localized in
      the envelope and did not exhibit any variation in molecular weight among all
      serotypes tested. The subcellular distribution of hemin binding activity may have
      functional implications.

PMID- 9038318
TI  - Involvement of mannose receptor in cytokine interleukin-1beta (IL-1beta), IL-6,
      and granulocyte-macrophage colony-stimulating factor responses, but not in
      chemokine macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC
      responses, caused by attachment of Candida albicans to macrophages.
AB  - The production of chemotactic cytokines (chemokines) and other cytokines by
      macrophages in response to fungal infection is thought to be critical during the
      course of candidiasis. However, the mechanism of cytokine synthesis by
      macrophages in response to fungi is not well understood. Therefore, the response
      of macrophages to Candida albicans was examined in terms of receptor-mediated
      chemokine and other cytokine mRNA induction. Attachment of C. albicans to murine
      thioglycollate-elicited peritoneal macrophages induced increased mRNA levels of
      the cytokines interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and the chemokines macrophage inflammatory
      protein 1beta (MIP-1beta), MIP-2, and KC (a member of the platelet factor 4
      neutrophil chemoattractant family), as determined by quantitative reverse
      transcription-PCR. However, treatment of macrophages with alpha-methyl-D
      mannoside significantly reduced the cytokine GM-CSF response to C. albicans but
      did not affect the chemokine MIP-2 response. Antisense oligodeoxynucleotide (ODN)
      to mannose receptor (MR) mRNA inhibited the expression and function of MR in
      macrophages as determined by Western blot analysis and 125I-labeled mannose
      bovine serum albumin (BSA) binding, and also inhibited the elevation of cytokine
      IL-1beta, IL-6, and GM-CSF mRNA levels induced by C. albicans attachment.
      Elevation of chemokine MIP-1beta, MIP-2, and KC mRNA levels induced by C.
      albicans was not affected in macrophages whose MR expression was suppressed by
      antisense ODN treatment. Furthermore, IL-4 treatment of macrophages, which up
      regulated MR expression as determined by Western blot analysis and fluorescein
      isothiocyanate-labeled mannose-BSA uptake, enhanced the level of cytokine GM-CSF
      mRNA induced by C. albicans but not the level of the chemokine MIP-2 mRNA. These
      results indicate that selected cytokine responses of macrophages to C. albicans
      are mediated by MR, while some chemokine responses may be mediated by other
      receptors.

PMID- 9038320
TI  - The Chlamydia trachomatis parasitophorous vacuolar membrane is not passively
      permeable to low-molecular-weight compounds.
AB  - Chlamydia trachomatis is an obligately intracellular bacterial parasite of
      eucaryotic cells that undergoes a biphasic life cycle within a parasitophorous
      vacuole (PV) called an inclusion. The parasitophorous vacuolar membrane (PVM)
      constitutes a barrier between the replicating bacteria and the nutrient-rich
      environment of the host cytoplasm. To determine whether the chlamydial PVM
      contains pores that allow passive diffusion of metabolites between the host
      cytoplasm and the PV, fluorescent tracer molecules were introduced directly into
      the cytoplasm of infected cells by transfection or microinjection. Fluorescence
      microscopy and laser scanning confocal microscopy were subsequently employed to
      determine whether equilibration of the fluorescent tracers between the cytoplasm
      and the PV occurred. No movement of tracer molecules as small as 520 Da from the
      cytoplasm to the PV was observed. These data suggest that the chlamydial PV is
      not passively permeable to small molecules through open channels in the PVM.

PMID- 9038321
TI  - Involvement of tubulin and inhibitory G proteins in the interaction of Listeria
      monocytogenes with mouse hepatocytes.
AB  - Intracellular and cell-to-cell spread of Listeria monocytogenes has been
      considered exclusively actin dependent. By immunocytochemical techniques, we
      provide evidence for an involvement of inhibitory G proteins and tubulin in
      "comet tail" formation in L. monocytogenes-infected mouse hepatocytes.

PMID- 9038322
TI  - Humoral immune responses of Solomon Islanders to the merozoite surface antigen 2
      of Plasmodium falciparum show pronounced skewing towards antibodies of the
      immunoglobulin G3 subclass.
AB  - The immunoglobulin G (IgG) subclass distribution of antibodies to merozoite
      surface antigen 2 of Plasmodium falciparum in Solomon Islanders showed marked
      skewing towards the IgG3 subclass. This was not observed with crude P. falciparum
      schizont antigen. IgG3 responses may be short-lived and require repeated
      restimulation for their maintenance. This may be provided by persistent infection
      (premunition) or new infections.

PMID- 9038323
TI  - Inducible expression of a Porphyromonas gingivalis W83 membrane-associated
      protease.
AB  - The Tpr protease of Porphyromonas gingivalis W83 is a membrane-associated enzyme
      capable of hydrolyzing a chromogenic bacterial collagenase substrate. An isogenic
      mutant lacking a functional tpr gene had a greatly reduced ability to hydrolyze
      the collagenase substrate. Activity was restored to the tpr mutant by introducing
      a shuttle plasmid containing the tpr gene. Expression of the gene is induced by
      nutrient limitation, as shown by enzymatic and Northern analyses.

PMID- 9038324
TI  - Positive regulation of Clostridium difficile toxins.
AB  - The toxigenic element of Clostridium difficile VPI 10463 contains a small open
      reading frame (ORF) immediately upstream of the toxin B gene (G. A. Hammond and
      J. L. Johnson, Microb. Pathog. 19:203-213, 1995). The deduced amino acid sequence
      of the ORF, which we have designated txeR, encodes a 22-kDa protein which
      contains a helix-turn-helix motif with sequence identity to DNA binding
      regulatory proteins. We used a DNA fragment containing the C. difficile toxin A
      repeating units (ARU) as a reporter gene to determine if txeR regulates
      expression from the toxin A and toxin B promoters in Escherichia coli. To test
      the affect of txeR on expression, we fused the ARU gene fragment in frame with
      the toxin promoters. The fusions expressed a 104-kDa protein that contained the
      epitopes for monoclonal antibody PCG-4, which we used to measure levels of
      recombinant ARU by enzyme-linked immunosorbent assay. When txeR was expressed in
      trans with the toxin B promoter-ARU fusion contained on separate low-copy-number
      plasmid, expression of ARU increased over 800-fold. Furthermore, when we tested
      the toxin A promoter fused to ARU, expression increased over 500-fold with txeR
      supplied in trans. Our results suggest that TxeR is a positive regulator that
      activates expression of the C. difficile toxins.

PMID- 9038325
TI  - A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic
      as falciparum malaria transmission-blocking vaccines.
AB  - Antibodies to Pfs28 block Plasmodium falciparum transmission and when combined
      with antibodies to Pfs25 provide synergy in blocking transmission. Pfs28 and
      Pfs25 are immunogenic, have limited antigenic diversity, and are structurally
      similar and genetically linked on chromosome 10. Pfs28 may prove a useful
      addition to Pfs25 in an effective transmission-blocking vaccine.

PMID- 9038326
TI  - Role of pertussis toxin A subunit in neutrophil migration and vascular
      permeability.
AB  - The anti-inflammatory activity of pertussis toxin (Ptx) was compared to that of a
      noncatalytic mutant of pertussis toxin (9K/129G; Ptxm), which contains two amino
      acid substitutions in the A protomer, by using a rat model of inflammation. The
      toxins were administered intravenously 1 h prior to the injection of inflammatory
      stimuli. Ptx, but not Ptxm, inhibited neutrophil migration into peritoneal
      cavities in response to formyl-methionyl-leucyl-phenylalanine and
      lipopolysaccharide. The inhibitory effect of Ptx on neutrophil migration could
      not be explained by the ability of the toxin to induce leukopenia or neutropenia.
      The increase in skin vascular permeability induced by leukotriene B4, a powerful
      neutrophil chemotactic agent, was also inhibited only by Ptx. On the other hand,
      the increase in skin vascular permeability induced by histamine was potentiated
      by both toxins. These data show that Ptx inhibits neutrophil-mediated
      inflammation in vivo and that this effect is dependent on the ADP
      ribosyltransferase activity of the A protomer.

PMID- 9038327
TI  - Innate immunity to Toxoplasma gondii is influenced by gender and is associated
      with differences in interleukin-12 and gamma interferon production.
AB  - Given that differences between the sexes in relative susceptibility to parasitic
      infections have been noted, this study further elucidates the mechanisms
      responsible by demonstrating that male SCID mice are more resistant than female
      mice to infection with Toxoplasma gondii and that this difference correlates with
      enhanced innate immune responses in these animals. Male SCID mice exhibited
      longer survival times, lower parasite burdens, and less severe pathological
      changes postinfection. An immunological basis for these differences is
      demonstrated in that these animals produced interleukin-12 more rapidly and
      exhibited higher levels of gamma interferon earlier postinfection.

PMID- 9038328
TI  - Interleukin-12 suppresses immunoglobulin E production but enhances immunoglobulin
      G4 production by human peripheral blood mononuclear cells.
AB  - The effect of interleukin-12 (IL-12) on human immunoglobulin G4 (IgG4) and IgE
      production was examined with cells derived from filarial patients and European
      controls. IL-12 inhibited IgE release but enhanced IgG4 production in cultures of
      peripheral blood mononuclear cells stimulated with anti-CD2 plus IL-2. When
      purified T- and B-cell cocultures were examined, IL-12 again markedly enhanced
      IgG4, whereas IgE production was no longer inhibited.

PMID- 9038330
TI  - Bile affects production of virulence factors and motility of Vibrio cholerae.
AB  - The effect of bile on the expression of cholera toxin (CT) and the major subunit
      of the toxin-coregulated pilus (TcpA) and on motility was examined in the Vibrio
      cholerae O1 classical-biotype strains 0395 and 569B. Although the motility of the
      cells increased significantly in the presence of bile, transcription of the ctxAB
      genes, encoding CT, and of the tcpA gene was drastically reduced. In toxR mutant
      strains, motility is higher than in the wild-type strain and was further
      increased, by about 150%, in the presence of bile. Bile represses CT production
      in strain 569B-55, a toxR mutant of strain 569B, which normally produces more
      than 80% of the amount of CT synthesized in the wild-type cells. These results
      suggest that bile may target some factor other than ToxR that is involved in the
      regulation of CT production and motility. Bile has no effect on the relative
      amounts of the two outer membrane porins, OmpU and OmpT, which are under ToxR
      control.

PMID- 9038329
TI  - Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus
      mutans in humans.
AB  - Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the
      Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19
      amino acids from a conserved region in the Gtfs (residues 435 to 453) were
      determined in young adults by enzyme-linked immunosorbent assay. Varying levels
      of antibody to Gtfs were detected in saliva or serum, with significantly higher
      levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva
      did not correlate with those of IgG in serum. Caries-free (CF) volunteers
      exhibited significantly higher salivary IgA antibody levels to the peptide and to
      GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF
      saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose
      dependent manner, whereas preincubation of the samples from the CA group resulted
      in only partial inhibition. Our results indicated that this 19-amino-acid peptide
      includes one of the major B-cell epitopes of Gtfs and that CF individuals have
      higher titers of antibodies than CA subjects.

PMID- 9038331
TI  - Terminology changes needed for descriptions of Pneumocystis carinii infection.

PMID- 9038332
TI  - ER quality control: the cytoplasmic connection.

PMID- 9038333
TI  - Organelle structure, function, and inheritance in yeast: a role for fatty acid
      synthesis?

PMID- 9038334
TI  - PI3K: downstream AKTion blocks apoptosis.

PMID- 9038335
TI  - Calreticulin.

PMID- 9038336
TI  - roX1 RNA paints the X chromosome of male Drosophila and is regulated by the
      dosage compensation system.
AB  - The Drosophila roX1 gene is X-linked and produces RNAs that are male-specific,
      somatic, and preferentially expressed in the central nervous system. These RNAs
      are retained in the nucleus and lack any significant open reading frame. Although
      all sexually dimorphic characteristics in Drosophila were thought to be
      controlled by the sex determination pathway through the gene transformer (tra),
      the expression of roX1 is independent of tra activity. Instead, the dosage
      compensation system is necessary and sufficient for the expression of roX1.
      Consistent with a potential function in dosage compensation, roX1 RNAs localize
      specifically to the male X chromosome. This localization occurs even when roX1
      RNAs are expressed from autosomal locations in X-to-autosome translocations. The
      novel regulation and subnuclear localization of roX1 RNAs makes them candidates
      for an RNA component of the dosage compensation machinery.

PMID- 9038337
TI  - Genes expressed in neurons of adult male Drosophila.
AB  - We have identified two genes, roX1 and roX2, whose expression in the adult fly is
      restricted to neurons of males. The two genes reside on the X chromosome, and
      each encodes an RNA with no apparent open reading frame. Both genes are
      physically linked to female-specific genes that encode proteins expressed in the
      ovary: opt1, a novel peptide transporter, and nod, a member of the kinesin
      family. The male-specific transcripts are positively regulated by the dosage
      compensation pathway in an all-or-none fashion. Our data suggest that the
      multimeric complex of dosage compensation proteins may operate in different ways
      on different sets of X-linked genes.

PMID- 9038338
TI  - MeCP2 is a transcriptional repressor with abundant binding sites in genomic
      chromatin.
AB  - MeCP2 is an abundant mammalian protein that binds to methylated CpG. We have
      found that native and recombinant MeCP2 repress transcription in vitro from
      methylated promoters but do not repress nonmethylated promoters. Repression is
      nonlinearly dependent on the local density of methylation, becoming significant
      at the density found in bulk vertebrate genomic DNA. Transient transfection using
      fusions with the GAL4 DNA binding domain identified a region of MeCP2 that is
      capable of long-range repression in vivo. Moreover, MeCP2 is able to displace
      histone H1 from preassembled chromatin that contains methyl-CpG. These
      properties, together with the abundance of MeCP2 and the high frequency of its 2
      bp binding site, suggest a role as a global transcriptional repressor in
      vertebrate genomes.

PMID- 9038339
TI  - HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of
      preintegration complexes in vitro.
AB  - We present data indicating that a host protein is important for function of HIV-1
      preintegration complexes (PICs) in vitro. PICs partially purified from infected
      cells were subjected to gel filtration in 600 mM KCl, which removed a factor
      required for integration without fully disrupting PICs. Addition of an extract
      from uninfected cells restored activity. Fractionation of the complementing
      activity yielded HMG I(Y), a nonhistone chromosomal protein important for
      transcriptional control and chromosomal architecture. Complementing activity
      could be isolated from PICs, and activity could be depleted from such fractions
      with an antibody against HMG I(Y). Recombinant HMG I(Y) also complemented salt
      stripped complexes. The finding that a host protein is required for integration
      by HIV PICs parallels findings in several well-studied transposition and site
      specific recombination systems.

PMID- 9038340
TI  - Coordinate binding of ATP and origin DNA regulates the ATPase activity of the
      origin recognition complex.
AB  - The Origin Recognition Complex (ORC) is a six-protein assembly that specifies the
      sites of DNA replication initiation in S. cerevisiae. Origin recognition by ORC
      requires ATP. Here, we demonstrate that two subunits, Orc1p and Orc5p, bind ATP
      and that Orc1p also hydrolyzes ATP. ATP binding and hydrolysis by Orc1p are both
      regulated by origin DNA in a sequence-specific manner. ATP binding to Orc1p, but
      not ATP hydrolysis, is responsible for the ATP dependence of the ORC-origin
      interaction, indicating that ATP is a cofactor that locks ORC on origin DNA.
      These data demonstrate that occupancy of the Orc1p ATP-binding site has a
      profound effect on ORC function and that ATP hydrolysis by Orc1p has the
      potential to drive transitions between different functional states of ORC.

PMID- 9038341
TI  - Nonhomologous RNA recombination in a cell-free system: evidence for a
      transesterification mechanism guided by secondary structure.
AB  - Extensive nonhomologous recombinations occur between the 5' and 3' fragments of a
      replicable RNA in a cell-free system composed of pure Qbeta phage replicase and
      ribonucleoside triphosphates, providing direct evidence for the ability of RNAs
      to recombine without DNA intermediates and in the absence of host cell proteins.
      The recombination events are revealed by the molecular colony technique that
      allows single RNA molecules to be cloned in vitro. The observed nonhomologous
      recombinations are entirely dependent on the 3' hydroxyl group of the 5'
      fragment, and are due to a splicing-like reaction in which RNA secondary
      structure guides the attack of this 3' hydroxyl on phosphoester bonds within the
      3' fragment.

PMID- 9038342
TI  - There is an upper limit of chromosome size for normal development of an organism.
AB  - A clearly definable upper tolerance limit for chromosome arm length has been
      found. As a rule we postulate that, for normal development of an organism, the
      longest chromosome arm must not exceed half of the average length of the spindle
      axis at telophase. Above this length, fertility and viability of the carrier
      individuals become severely impaired due to increasingly incomplete separation of
      the longest chromatids during mitosis, resulting finally in the loss of DNA. The
      experimental work that points to a limit in genome plasticity has been carried
      out on a series of field bean lines with karyotypes of considerable variation in
      length of individual chromosomes.

PMID- 9038343
TI  - Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP
      kinase pathway.
AB  - Rapid modulation of ligand binding affinity ("activation") is a central property
      of the integrin cell adhesion receptors. Using a screen for suppressors of
      integrin activation, we identified the small GTP-binding protein, H-Ras, and its
      effector kinase, Raf-1, as negative regulators of integrin activation. H-Ras
      inhibited the activation of integrins with three distinct alpha and beta subunit
      cytoplasmic domains. Suppression was not associated with integrin phosphorylation
      and was independent of both mRNA transcription and protein synthesis.
      Furthermore, suppression correlated with activation of the ERK MAP kinase
      pathway. Thus, regulation of integrin affinity state is a novel, transcription
      independent function of a Ras-linked MAP kinase pathway that may mediate a
      negative feedback loop in integrin function.

PMID- 9038344
TI  - The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via
      the exchange factor ROM2.
AB  - The Saccharomyces cerevisiae phosphatidylinositol kinase homolog TOR2 is required
      for organization of the actin cytoskeleton. Overexpression of RHO1 or RHO2,
      encoding Rho-like GTPases, or ROM2, encoding a GDP/GTP exchange factor for RHO1
      and RHO2, suppresses a tor2 mutation. Deletion of SAC7, a gene originally
      identified as a suppressor of an actin mutation, also suppresses a tor2 mutation.
      SAC7 is a novel GTPase-activating protein for RHO1. ROM2 exchange activity is
      reduced in a tor2 mutant, and overexpression of ROM2 lacking its PH domain can no
      longer suppress a tor2 mutation. Thus, TOR2 signals to the actin cytoskeleton
      through a GTPase switch composed of RHO1, RHO2, ROM2, and SAC7. TOR2 activates
      this switch via ROM2, possibly via the ROM2 PH domain.

PMID- 9038345
TI  - Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion.
AB  - Mitotic gene conversion acting as reverse mutation has not been previously
      demonstrated in human. We report here that the revertant mosaicism of a compound
      heterozygous proband with an autosomal recessive genodermatosis, generalized
      atrophic benign epidermolysis bullosa, is caused by mitotic gene conversion of
      one of the two mutated COL17A1 alleles. Specifically, the maternal allele
      surrounding the mutation site on COL17A1 (1706delA) showed reversion of the
      mutation and loss of heterozygosity along a tract of at least 381 bp in revertant
      keratinocytes derived from clinically unaffected skin patches; the paternal
      mutation (R1226X) remained present in all cell samples. Revertant mosaicism
      represents a way of natural gene therapy.

PMID- 9038346
TI  - Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated
      in cystic fibrosis.
AB  - A human bronchial xenograft model was used to characterize the molecular basis
      for the previously described defect in bacterial killing that is present in the
      cystic fibrosis (CF) lung. Airway surface fluid from CF grafts contained
      abnormally high NaCl and failed to kill bacteria, defects that were corrected
      with adenoviral vectors. A full-length clone for the only known human beta
      defensin (i.e., hBD-1) was isolated. This gene is expressed throughout the
      respiratory epithelia of non-CF and CF lungs, and its protein product shows salt
      dependent antimicrobial activity to P. aeruginosa. Antisense oligonucleotides to
      hBD-1 ablated the antimicrobial activity in airway surface fluid from non-CF
      grafts. These data suggest that hBD-1 plays an important role in innate immunity
      that is compromised in CF by its salt-dependent inactivation.

PMID- 9038347
TI  - Development of a novel polygenic model of NIDDM in mice heterozygous for IR and
      IRS-1 null alleles.
AB  - NIDDM is a polygenic disease characterized by insulin resistance in muscle, fat,
      and liver, followed by a failure of pancreatic beta cells to adequately
      compensate for this resistance despite increased insulin secretion. Mice double
      heterozygous for null alleles in the insulin receptor and insulin receptor
      substrate-1 genes exhibit the expected approximately 50% reduction in expression
      of these two proteins, but a synergism at a level of insulin resistance with 5-
      to 50-fold elevated plasma insulin levels and comparable levels of beta cell
      hyperplasia. At 4-6 months of age, 40% of these double heterozygotes become
      overtly diabetic. This NIDDM mouse model in which diabetes arises in an age
      dependent manner from the interaction between two genetically determined,
      subclinical defects in the insulin signaling cascade demonstrates the role of
      epistatic interactions in the pathogenesis of common diseases with non-Mendelian
      genetics.

PMID- 9038348
TI  - Possible roles of inositol 1,4,5-trisphosphate 3-kinase B in calcium homeostasis.
AB  - Some aspects of the roles of inositol trisphosphate (Insp3) and inositol
      tetrakisphosphate (Insp4) in Ca2+ homeostasis in terms of inositol trisphosphate
      3-kinase B (IP3K-B) localization and activity are discussed. The model that we
      propose is also compatible with IP3K-B participating in the widely reported
      phenomenon of quantal release of Ca2+ from internal stores, at least in some
      biological systems.

PMID- 9038349
TI  - Identification of the amino acid residues responsible for cold tolerance in
      Flaveria brownii pyruvate,orthophosphate dikinase.
AB  - Pyruvate,orthophosphate dikinase (PPDK), an enzyme important in C4
      photosynthesis, is typically a cold-sensitive enzyme. However, a cold-tolerant
      form of the enzyme has been isolated from the leaves of Flaveria brownii. Using
      an E. coli expression system and the PPDK cDNAs from F. brownii (cold-tolerant),
      F. bidentis (cold-sensitive) and maize (intermediately cold-tolerant), site
      directed mutagenesis studies indicated that as few as three amino acids residues
      (of 880 residues) strongly influence the cold sensitivity of Flaveria PPDK. Gel
      filtration analysis of the PPDK expressed in E. coli showed that subunit
      association and cold tolerance are closely linked.

PMID- 9038350
TI  - Anaerobic carotenoid biosynthesis in Rhodobacter sphaeroides 2.4.1: H2O is a
      source of oxygen for the 1-methoxy group of spheroidene but not for the 2-oxo
      group of spheroidenone.
AB  - Anaerobic biosynthesis of carotenoids in the purple facultative photosynthetic
      bacterium Rhodobacter sphaeroides was studied using mass spectrometry. We have
      demonstrated that (18)O from H2(18)O was incorporated into the 1-methoxy group of
      spheroidene and spheroidenone, the two major carotenoids produced by this
      bacterium during photosynthetic growth. Neither water nor CO2 was shown to
      provide an oxygen atom for the 2-oxo group of spheroidenone in R. sphaeroides
      2.4.1 grown photosynthetically in the absence of molecular oxygen. Possible
      mechanisms for the anaerobic biosynthesis of spheroidenone in R. sphaeroides are
      discussed.

PMID- 9038351
TI  - Import inhibition of poly(His) containing chloroplast precursor proteins by Ni2+
      ions.
AB  - The precursor of the small subunit of ribulose-1,5-bisphosphate carboxylase (pSS)
      and a modified pSS containing a C-terminal hexahistidyl tail (pSS(His)6) were
      imported into isolated Chlamydomonas chloroplasts with comparable efficiency. In
      the presence of Ni2+ ions the import of pSS(His)6 was inhibited and the precursor
      bound to the envelope remained protease sensitive, while import of pSS was not
      affected. Addition of an excess of L-histidine suppressed the inhibition
      demonstrating that the hexahistidyl-Ni2+ complex was responsible for import
      inhibition. Inhibition could be observed between about 0.5 and 10 mM Ni2+,
      depending on the total protein content in the assay. Import incompetent Ni2+ 
      precursor complexes can be used to study early events in chloroplast protein
      import.

PMID- 9038352
TI  - Identification and characterization of a predominant isoform of human MKK3.
AB  - We have obtained a novel cDNA species of MKK3, termed MKK3b. MKK3b cDNA differs
      from its original form, MKK3, at the 5'-end, encoding 29 extra amino acids in the
      N-terminus. Analysis of MKK3 genomic DNA structure revealed that the MKK3b-unique
      5'-end sequence is derived from an exon different from that of MKK3, and that
      they share identical sequences thereafter. This suggests that the two cDNA forms
      of MKK3 are either generated by differential splicing of the same gene or derived
      from differential promoter utilization. Northern blotting analysis showed that
      MKK3b mRNA is much more abundant than MKK3. Functional characterization based on
      the activation of p38 revealed that MKK3b is more efficient than MKK3 in
      mediating downstream signalling events.

PMID- 9038353
TI  - Activation of p21-activated protein kinase alpha (alpha PAK) by hyperosmotic
      shock in neonatal ventricular myocytes.
AB  - The p21-activated protein kinases (PAKs) may participate in signalling from
      Cdc42/Rac1 to the stress-regulated MAPKs (SAPKs/JNKs and p38-/HOG-1-related
      MAPKs). We characterized the expression and regulation of alpha PAK in cultured
      ventricular myocytes. alpha PAK was specifically immunoprecipitated from myocyte
      extracts. High basal alpha PAK activity was detected in unstimulated myocytes.
      Its activity was increased rapidly (<30 s) by hyperosmotic shock in the presence
      of okadaic acid, and was maximal by 3 min (187 +/- 7% relative to unstimulated
      cells). Endothelin-1 and interleukin-1beta, which also activate SAPKs/JNKs, did
      not increase alpha PAK activity and presumably act through different PAK isoforms
      or other mechanisms.

PMID- 9038354
TI  - The P2Y1 receptor is an ADP receptor antagonized by ATP and expressed in
      platelets and megakaryoblastic cells.
AB  - The human P2Y1 purinoceptor has been expressed in Jurkat cells and the effects of
      HPLC purified nucleotides on calcium movements were measured. The most potent
      agonist was 2-methylthio-ADP followed by ADP. ATP, Sp-ATPalphaS and beta,gamma
      methylene-ATP were competitive antagonists. Suramin and PPADS inhibited the
      effects of ADP. This pharmacological profile is the same as that of the so-called
      P2T purinoceptor responsible for platelet aggregation, which has not yet been
      identified. Using PCR we found the P2Y1 receptor to be present in blood platelets
      and megakaryoblastic cell lines. These data suggest that the P2Y1 receptor may be
      the elusive P2T receptor.

PMID- 9038355
TI  - The vav proto-oncogene product (p95vav) interacts with the Tyk-2 protein tyrosine
      kinase.
AB  - The vav proto-oncogene product participates in the signaling pathways activated
      by various cell-surface receptors, including the type I IFN receptor. During
      engagement of the type I IFN receptor, p95vav is phosphorylated on tyrosine
      residues, but the kinase regulating its phosphorylation has not been identified
      to date. Our studies demonstrate that p95vav forms a stable complex with the IFN
      receptor-associated Tyk-2 kinase in vivo, and strongly suggest that this kinase
      regulates its phosphorylation on tyrosine. Thus, p95vav is engaged in IFN
      signaling by a direct interaction with the functional type I IFN receptor complex
      to transduce downstream signals.

PMID- 9038356
TI  - Ras GTPase-activating protein-associated p62 is a major v-Src-SH3-binding
      protein.
AB  - Oncogenic transformation by v-Src is accompanied by marked morphological changes
      and cytoskeletal reorganization. Yet, the cytoskeleton-associated proteins with
      which v-Src interacts are largely unknown. We have studied the binding of v-Src
      SH3 domain to cellular proteins utilizing a blot overlay procedure with a GST-v
      Src-SH3 fusion protein as probe. A major 62-64 kDa v-Src-SH3-binding protein,
      present in detergent-insoluble cellular fractions, was identified as p21ras
      GTPase-activating protein-associated p62 (GAPA62). In non-transformed cells,
      including NIH 3T3 cells, GAPA62 was present in both the RIP A-soluble and RIP A
      insoluble fractions, but only the latter form was tyrosine-phosphorylated. In
      contrast, in polyoma middle T antigen-transformed 3T3 cells, GAPA62 was present
      only in the RIP A-insoluble fraction, where it was highly phosphorylated. It is
      suggested that tyrosine phosphorylation of GAPA62 may be an important determinant
      of its cellular localization and its possible function as a mediator of v-Src
      actions.

PMID- 9038358
TI  - Growth-dependent subnuclear localization of a 66 kDa phosphoprotein in FER
      protein overexpressing cells.
AB  - p94fer and p51ferT are two nuclear tyrosine kinases encoded by the FER locus in
      the mouse. While p94fer accumulates in somatic cells, p51ferT is found solely in
      meiotic spermatogenic cells. Ectopic expression of p94fer or p51ferT in CHO
      cells, led to tyrosine phosphorylation of cellular 66, 68 and 120 kDa proteins. A
      120, 68 and 66 kDa phosphoproteins, coimmunoprecipitated with p94fer and p51ferT
      from extracts of transfected CHO cells. Subcellular fractionation analysis
      indicated that the 66 kDa tyrosine phosphorylated protein colocalizes with
      p51ferT to perinuclear and nuclear fractions in actively growing cells. However,
      in growth arrested cells, the 66 kDa phosphoprotein was associated mainly with
      chromatin while its level in the other nuclear compartments was significantly
      reduced. The 66 kDa phosphoprotein may thus mediate the nuclear function of the
      FER proteins and link it to cell growth.

PMID- 9038357
TI  - Potent inhibition of inducible nitric oxide synthase by geldanamycin, a tyrosine
      kinase inhibitor, in endothelial, smooth muscle cells, and in rat aorta.
AB  - We have examined whether specific protein tyrosine kinase (PTK) inhibitors
      (genistein, tyrphostin, or geldanamycin) prevent nitric oxide (NO.) production in
      rat smooth muscle cells (SMC), in murine brain endothelial cells (MBE), and in
      isolated rat aortas treated with endotoxin (LPS) and/or cytokines. Tyrphostin
      failed to inhibit either the release of nitrite in both endothelial and smooth
      muscle cells or vascular hyporeactivity in rat aorta, caused by immunostimulants.
      Genistein decreased nitrite production in MBE only at high concentration but had
      no effect on nitrite production in SMC and on the hypocontractility in aortic
      rings. In contrast, low concentrations of geldanamycin abolished the release of
      nitrite in MBE and in SMC treated with endotoxin and/or cytokines. Geldanamycin
      inhibited also the hypocontractility to phenylephrine in aortic rings treated
      with LPS or interleukin-1. This inhibitor failed to inhibit the release of
      nitrite and the vascular hyporeactivity once nitric oxide synthase (NOS) was
      induced by immunostimulants whereas methyl-L-arginine, an inhibitor of NOS, had
      significant effects. These data suggest that LPS- and cytokines-induced NO.
      production initiate a common signaling pathway involving a PTK that is inhibited
      by geldanamycin but not or slightly by tyrphostin or genistein at a point that
      precedes the induction of NOS.

PMID- 9038359
TI  - Crystallographic investigation of the dependence of calcium and phosphate ions
      for notexin.
AB  - The crystal structure of the neurotoxic phospholipase A2, notexin, revealed three
      binding sites for sulphate ions which were suggested to be phosphate binding
      sites of importance for the activity of the toxin. The present investigation
      shows that the sulphate ion bound to the major binding site alters the structure
      of residues 60-75. In the absence of sulphate and phosphate, the structure of
      this loop has a conformation which partly resembles the non-neurotoxic PLA2s. The
      affinity of notexin for phosphate is 17 microM, as measured by the increase in
      fluorescence at 345 nm. Since the concentrations of phosphate and sulphate ions
      in blood plasma are 3 and 1 mM, respectively, the binding site must be occupied
      under physiological conditions. This major sulphate/phosphate binding site
      explains the specific affinity labelling by pyridoxal phosphate. Pyridoxal
      phosphate binds to this anion binding site which allows the reaction with Lys-88
      or Lys-89. The structure of notexin in the presence and absence of Ca2+ shows
      only small local structural differences.

PMID- 9038360
TI  - Transforming growth factor-beta1 induces activation of Ras, Raf-1, MEK and MAPK
      in rat hepatic stellate cells.
AB  - The transdifferentiation of hepatic stellate cells into myofibroblast-like cells
      and the proliferation of the transdifferentiated cells are controlled by TGF
      beta1. Little is known about the intracellular signal transducers of TGF-beta1.
      In this paper we show that in cultured hepatic stellate cells TGF-beta1 induces
      activation of Ras, Raf-1, MEK and MAPK p42 and p44. The activation of MAPK
      depends on the activation of MEK. Our data exclude that the observed effects are
      mediated by a bFGF or PDGF autocrine loop.

PMID- 9038361
TI  - Characterization of seven murine caspase family members.
AB  - Seven members of the murine caspase (mCASP) family were cloned and functionally
      characterized by transient overexpression: mCASP-1 (mICE), mCASP-2 (Ich1), mCASP
      3 (CPP32), mCASP-6 (Mch2), mCASP-7 (Mch3), mCASP-11 (TX) and mCASP-12. mCASP-11
      is presumably the murine homolog of human CASP-4. Although mCASP-12 is related to
      human CASP-5 (ICErel-III), it is most probably a new CASP-1 family member. On the
      basis of sequence homology, the caspases can be divided into three subfamilies:
      first, mCASP-1, mCASP-11 and mCASP-12; second, mCASP-2; third, mCASP-3, mCASP-6
      and mCASP-7. The tissue distribution of the CASP-1 subfamily transcripts is more
      restricted than that of the CASP-3 subfamily transcripts, suggesting that the
      transcriptional regulation of the CASP members within one subfamily is related,
      but is quite different between the CASP-1 and the CASP-3 subfamilies. Transient
      overexpression of each of the seven CASPs induced apoptosis in mammalian cells.
      Only two, mCASP-1 as well as mCASP-3, were able to process precursor interleukin
      (IL)-1beta to biologically active IL-1beta. In addition, mCASP-3 is the
      predominant PARP-cleaving enzyme in vivo.

PMID- 9038362
TI  - Reciprocal protection of LDL and HDL oxidised by .OH free radicals in the
      presence of oxygen.
AB  - The aim of this work was to compare the behaviour of HDL oxidised by .OH or
      .OH/O2.- free radicals produced by gamma radiolysis in the absence or in the
      presence of LDL at the same concentration of 3 g x l(-1), in order to specify the
      possibility of reciprocal protection of HDL and LDL towards lipid peroxidation.
      This oxidation was quantitatively evaluated by the decrease of endogenous alpha
      tocopherol and the formation of oxidation products (thiobarbituric acid-reactive
      substances and conjugated dienes) and by the determination of initial radiation
      yields. Our results demonstrated that HDL could be protected by LDL against in
      vitro radical oxidation only in the presence of oxygen (action of .OH/O2.- free
      radicals). This observation addresses new questions about the interaction between
      HDL and LDL, especially the possibility of a reciprocal protection.

PMID- 9038363
TI  - Identification of a specific amino acid cluster in the calmodulin-binding domain
      of the neuronal nitric oxide synthase.
AB  - The calmodulin (CaM) binding domain of rat neuronal nitric oxide synthase (nNOS)
      was analyzed using 3 synthetic peptides corresponding to different regions of the
      middle portion of the enzyme. One corresponding to nNOS 732-754 gave complete
      inhibition of NOS enzyme activity with an IC50 of about 1 microM. Kinetic
      analysis indicated that the inhibition was not competitive with respect to L
      arginine and the peptide produced a Ca2+ dependent, electrophoretic mobility
      shift of CaM on 1 M urea gels. A specific hydrophobic/basic amino acid cluster in
      the rat nNOS sequence, Lys732 Lys Leu, that was critical for its CaM binding was
      also identified in this study.

PMID- 9038365
TI  - Expression of human TRPC genes in the megakaryocytic cell lines MEG01, DAMI and
      HEL.
AB  - Store-regulated Ca2+ entry represents a major mechanism for Ca2+ influx in non
      excitable cells although many details remain to be evaluated including the
      identification of cation entry channels. Recently human homologues of the
      Drosophila proteins TRP and TRPL, have been described (TRPC1, TRPC1A, HTRP1) and
      suggested as candidate cation channels. In this study we sought to examine if the
      producers of blood platelets, megakaryocytic cells (using the cell lines MEG01,
      DAMI, HEL), expressed these genes. RNA was prepared from the cell lines and
      platelets and converted to cDNA. The cDNA was then subjected to 30-35 cycles of
      PCR using gene specific primers for TRPC1-3. PCR products of the expected sizes
      were observed for all three TRPC genes in the three cell lines. Direct sequencing
      confirmed their identity. Additionally for TRPC1, a larger species, and for
      TRPC2, a smaller species was detected in all three cell lines with sequencing
      revealing the fragments to contain TRPC sequence, suggesting that they were
      either products of alternative splicing events or from closely related genes.
      These results suggest that TRPC genes are expressed in megakaryocytic cell lines
      and that the TRPC proteins may play a role in mediating cation influx in both
      megakaryocytes and platelets.

PMID- 9038364
TI  - Leptin receptor (OB-R) oligomerizes with itself but not with its closely related
      cytokine signal transducer gp130.
AB  - Leptin (OB) exerts weight-reducing effects in mice. The structure of the receptor
      for this factor, OB-R, is considerably similar to those of gp130, the common
      signal transducing receptor component for the interleukin-6 (IL-6) family of
      cytokines, and leukemia inhibitory factor receptor (LIFR). Since the IL-6 family
      of cytokines signal through gp130 homodimer or gp130/LIFR heterodimer, we have
      examined in this study the possible involvement of gp130 and LIFR in leptin
      signaling through OB-R. Leptin stimulation induces tyrosine phosphorylation of
      neither gp130 nor LIFR, while LIF stimulation does both. As examined by using two
      differently epitope-tagged OB-R molecules, the spontaneous homo-oligomerization
      of OB-R has been elucidated. Ba/F3 cells, which do not express gp130, are non
      responsive to leptin and exhibit increased DNA synthesis in response to leptin
      after transfection of OB-R cDNA alone. OB-R appears to transduce the signal via
      its homo-oligomerization without interaction with gp130 or LIFR.

PMID- 9038366
TI  - Redox-regulated expression of glycolytic enzymes in resting and proliferating rat
      thymocytes.
AB  - Resting rat thymocytes partially degrade glucose aerobically to CO2 and H2O and
      produce reactive peroxide anions. In contrast proliferating cells, due to
      enhanced induction of glycolytic enzymes, degrade glucose almost completely to
      lactate thus minimizing the production of reactive oxygen species. In this paper
      we show that under conditions of oxidative stress the induction of the glycolytic
      enzymes in cultured rat thymocytes is markedly reduced. Furthermore, transfection
      assays with a rat hepatoma cell line and Drosophila Schneider cells revealed that
      reactive oxygen intermediates dramatically decrease the transcriptional
      activities of the Sp1-dependent aldolase A and pyruvate kinase M2 promoters
      leading to reduced reporter gene expression. These results indicate that cellular
      redox changes can regulate gene expression by reversible oxidative inactivation
      of Sp1 binding.

PMID- 9038368
TI  - Yeast RAS2 mutations modulating the ras-guanine exchange factor interaction.
AB  - We have used a two-hybrid approach to test various forms of Saccharomyces
      cerevisiae Ras2p for their ability to interact with the human guanine nucleotide
      exchange factor HGRF55. We have previously shown that a strong two-hybrid
      interaction is found between the HGRF55p and the dominant negative Ras2p(G22A)
      form of ras [Camus et al. (1995) Oncogene 11, 951-959]. We show here that the
      substitution N123I which weakens the guanine nucleotide binding also promotes ras
      GEF interaction. We demonstrate that the R80D substitution alone completely
      abolishes the interaction of Ras2p(G22A) with GEF, whereas substitutions at
      positions 81, 82 and 73 have only small effects. Since residue 73 is involved in
      the response of ras to GEF, we propose that it plays a role in the conformational
      change induced by the GEF rather than in its binding. Those results emphasize the
      role of the alpha2 helix of the switch II region in the recognition of the GEF
      family.

PMID- 9038367
TI  - Functional expression, activation and desensitization of opioid receptor-like
      receptor ORL1 in neuroblastoma x glioma NG108-15 hybrid cells.
AB  - Neuroblastoma x glioma NG108-15 hybrid cells have been examined for the
      expression of opioid receptor-like receptor (ORL1). [3H]Nociceptin/orphanin FQ
      (OFQ) bound to the cell membrane specifically (Kd = 3.6 +/- 0.6 nM) and inhibited
      forskolin-stimulated cAMP accumulation (EC50 = 0.72 +/- 0.3 nM). The
      responsiveness of NG108-15 cells to nociceptin/OFQ was blocked by pertussis toxin
      but not by naltrindole. The inhibitory activity of nociceptin/OFQ was
      significantly reduced after a prechallenge with the same peptide but was not
      influenced by DPDPE pretreatment, indicating acute and homologous desensitization
      of ORL1 receptors. Naltrindole caused the overshoot of cAMP in DPDPE-pretreated
      cells but not in nociceptin/OFQ-pretreated cells. The results indicate that ORL1
      is functionally expressed and does not cross-interact with specific ligands of
      the delta opioid receptor in NG108-15 cells.

PMID- 9038369
TI  - Dexamethasone differently modulates TNF-alpha- and IL-1beta-induced transcription
      of the hepatic Mn-superoxide dismutase gene.
AB  - The effects of cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta), and the synthetic glucocorticoid dexamethasone on the gene
      expression of antioxidant enzymes have been investigated in rat hepatocytes in
      primary culture. First, we observed that the hepatocyte culture process induced a
      strong but transient induction of manganese superoxide dismutase (Mn-SOD) gene
      expression, whereas copper-zinc superoxide dismutase, glutathione peroxidase and
      catalase genes were down-regulated. IL-1beta and TNF-alpha both stimulated
      specifically Mn-SOD gene expression in a time-dependent manner. TNF-alpha rapidly
      induced Mn-SOD gene expression while IL-1beta was a strong but slow inducer of
      this gene. Both cytokines acted at the transcriptional level as shown by nuclear
      run on assays. Dexamethasone prevented the TNF-alpha- but not the IL-1beta
      induced up-regulation of Mn-SOD gene transcription by a mechanism likely to
      involve the glucocorticoid receptor. Moreover this glucocorticoid did not
      suppress the TNF-alpha-induced increase of NF-kappaB binding activity. These
      results suggest that IL-1beta and TNF-alpha regulate Mn-SOD gene transcription by
      different pathways.

PMID- 9038370
TI  - PCNA: structure, functions and interactions.
AB  - Proliferating cell nuclear antigen (PCNA) plays an essential role in nucleic acid
      metabolism as a component of the replication and repair machinery. This toroidal
      shaped protein encircles DNA and can slide bidirectionally along the duplex. One
      of the well-established functions for PCNA is its role as the processivity factor
      for DNA polymerase delta and epsilon. PCNA tethers the polymerase catalytic unit
      to the DNA template for rapid and processive DNA synthesis. In the last several
      years it has become apparent that PCNA interacts with proteins involved in cell
      cycle progression which are not a part of the DNA polymerase apparatus. Some of
      these interactions have a direct effect on DNA synthesis while the roles of
      several other interactions are not fully understood. This review summarizes the
      structural features of PCNA and describes the diverse functions played by the
      protein in DNA replication and repair as well as its possible role in chromatin
      assembly and gene transcription. The PCNA interactions with different cellular
      proteins and the importance of these interactions are also discussed.

PMID- 9038371
TI  - The DFer gene of Drosophila melanogaster encodes two membrane-associated proteins
      that can both transform vertebrate cells.
AB  - The vertebrate gene FER encodes two protein-tyrosine kinases with molecular
      weights of 51,000 and 94,000 and distinctive aminotermini. The larger kinase is
      expressed ubiquitously among vertebrate tissues, whereas expression of the
      smaller kinase appears to be limited to spermatogenic cells in the testes. Here
      we show that Drosophila melanogaster contains an apparent ortholog of FER (DFer)
      that also produces two mRNAs by separate initiation of transcription, and two
      proteins with molecular weights of 45,000 and 92,000. Both proteins are in part
      loosely associated with cytoplasmic membranes. Both can transform avian and
      rodent cells with roughly equal potency, when expressed from retroviral vectors.
      Fusing the myristoylation signal from the SRC protein-tyrosine kinase to the
      aminoterminus of the DFer protein increased the strength of attachment to
      membranes but augmented transformation only marginally. The results provide the
      first demonstration of neoplastic transformation by a protein-tyrosine kinase of
      Drosophila and by FER from any species. The products of Drosophila and vertebrate
      FER may be part of similar signaling pathways in the two species.

PMID- 9038372
TI  - A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase.
AB  - STE20-homologous proteins have been implicated in mammalian MAP kinase pathways
      as important transducers of signals from p21 family GTPases. We have cloned a
      novel STE20 family member, which we call KHS for kinase homologous to SPS1/STE20,
      that encodes a kinase of 95 kD which is expressed in a variety of tissues.
      Transiently expressed fusion protein GST-KHS exhibits phosphotransferase activity
      toward a panel of test substrates, including myelin basic protein (MBP), which is
      phosphorylated by all known STE20 homologues. KHS is most closely related to
      another human STE20, GC kinase (74% similar in the catalytic domain), which has
      recently been placed upstream of the stress-activated MAP kinases (SAPKs/JNKs).
      KHS also activates JNK in transient coexpression experiments, suggesting a role
      for KHS in the stress response of fibroblasts. Characterization and comparison of
      the regulation of these two kinases will be important in elucidating MAP kinase
      signalling cascades.

PMID- 9038373
TI  - Expression and function of members of the cytokine receptor superfamily on breast
      cancer cells.
AB  - Receptors for the cytokines leukemia inhibitory factor (LIF), interleukin-6 (IL
      6), oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and interleukin-11 (IL
      11) are members of the structurally conserved hemopoietin receptor superfamily.
      In addition, they all share the transmembrane signalling protein gp130. In this
      paper the expression and function of this family of receptors in breast cancer
      cells was examined. RT-PCR analyses demonstrated that gp130 was expressed in
      12/12 breast cell lines and the specific receptor alpha-chains for IL-6, LIF, IL
      11 and CNTF were expressed in the majority of these cell lines. This was in
      contrast to other hemopoietin receptors. Examination of 50 clinical samples of
      malignant breast tissue by RT-PCR showed a similar pattern of expression of gp130
      associated receptors. Treatment of breast cancer cell lines with OSM resulted in
      changes in cellular morphology. Cellular proliferation was inhibited following
      exposure to OSM (3/4 cell lines), IL-11 (2/4 cell lines), and by IL-6 and LIF
      (1/4 cell lines). Cell surface binding of LIF and OSM was also documented. The
      expression of these receptors in 12/12 cell lines and greater than 95% of
      clinical samples suggests that these molecules may be important in regulating the
      growth of breast cells.

PMID- 9038374
TI  - FGF-2 and FGF-1 expressed in rat bladder carcinoma cells have similar angiogenic
      potential but different tumorigenic properties in vivo.
AB  - The comparative biological properties of NBT-II cells, a rat bladder carcinoma
      cell line constitutively expressing FGF-1 and FGF-2 were analysed in nude mice.
      FGF-1 is not secreted by the transfected cells unless the cDNA contains a signal
      sequence; conversely, NBT-II cells transfected with FGF-2 coding sequence produce
      and secrete the factor in a biologically active form. Bovine brain capillary
      endothelial cells are stimulated to proliferate upon addition of medium
      conditioned by the FGF-2-producing cells and this activity can be abrogated by
      the addition of anti-FGF-2 blocking antibodies. In addition, the FGF-2-containing
      medium, which cannot stimulate NBT-II cells due to absence of appropriate
      receptors, is able to induce scattering of NBT-II cells expressing the FGFR1. It
      has been reported previously that FGF-1-producing cells are highly tumorigenic in
      nude mice and induce carcinoma with a period of latency reduced from 6 to 5 weeks
      when compared to parental NBT-II cells. In contrast, NBT-II cells producing FGF-2
      are no more tumorigenic than parental cells, indicating that FGF-1 and FGF-2 have
      different oncogenic properties in carcinoma. FGF-1 and FGF-2 are potent
      antiogenic factors that trigger the host endothelial cells. VEGF, another potent
      angiogen was found to be expressed in small amounts by NBT-II cells and to be
      expressed in reduced amount in the FGF-producing cells. In the NBT-II system in
      vivo FGF-1 and FGF-2 are highly and comparatively angiogenic in the resultant
      carcinoma and this occurs in the absence of production of significant amounts of
      VEGF by the carcinoma cells. Taken together, our results indicate that activated
      angiogenesis is not sufficient for rapid tumor expansion. FGF-1 behaves as a
      tumorigenic factor in the NBT-II bladder carcinoma cell model, whereas expression
      and secretion of large amounts of FGF-2 are not sufficient for increasing tumor
      growth.

PMID- 9038375
TI  - Ectopic expression of a mutant form of PKCalpha originally found in human tumors:
      aberrant subcellular translocation and effects on growth control.
AB  - A point mutation in PKCalpha was originally discovered in a subpopulation of
      human pituitary tumors characterized by their invasive phenotype, and the same
      mutation was also seen in some thyroid neoplasms. To investigate the role of this
      mutation in tumorigenesis, normal and mutant human PKCalpha cDNAs were
      overexpressed in Rat6 embryo fibroblasts (R6). When extracts of R6 cells that
      expressed either the normal or mutant PKCalpha were assayed in the presence of
      calcium, phosphatidylserine and the phorbol ester TPA, for phosphorylation of
      either histone IIIS or the EGF-receptor peptide, both extracts gave similar
      results. However, the subcellular localization of the two proteins differed.
      Immunohistochemistry studies indicated that after treatment with TPA normal
      PKCalpha mainly translocated to the plasma membrane, but mutant PKCalpha
      translocated mainly to the perinuclear region and slightly to the nucleus.
      Furthermore, the cells that expressed the mutant PKCalpha displayed a decreased
      requirement for serum when compared to the cells expressing the normal human
      PKCalpha, and they formed small colonies in soft agar. By contrast, the cells
      expressing the normal human PKCalpha failed to form colonies in soft-agar. Thus,
      ectopic expression in rat fibroblasts of this mutant human PKCalpha sequence
      alters the growth properties of these cells and, when activated, the mutant
      PKCalpha displays aberrant intracellular translocation. Therefore, this mutation
      in PKCalpha could contribute to the process of tumor progression in certain human
      tumors.

PMID- 9038376
TI  - Dimerization of the p185neu transmembrane domain is necessary but not sufficient
      for transformation.
AB  - The neu proto-oncogene encodes a receptor tyrosine kinase (RTK). The oncogenic
      allele neu* (p185*) bears a glutamic acid for valine substitution at position 664
      within the predicted transmembrane domain. We have used this mutant to explore
      the role of the transmembrane domain in signal transduction by RTKs. Analysis of
      a panel of neu* proteins with second-site mutations in the transmembrane domain
      revealed a strong correlation of dimerization with transformation. Both
      dimerization and transformation are dependent on a domain formed by the amino
      acids Val663-Glu664-Gly665 (VEG). However, movement of the VEG elsewhere within
      the transmembrane domain promoted weak dimerization but not transformation.
      Epidermal growth factor receptor (EGFR)/neu chimeras were used to determine if
      mutations that disrupt activation by Glu664 affect hormone-regulated signal
      transduction as well. These mutations (of Val663 and Gly665) did not affect
      regulation by EGF. Introduction of the known transmembrane dimerization domain
      from Glycophorin A (GpA) stimulated dimerization, but was not sufficient for
      transformation. These results indicate that dimerization is necessary but not
      sufficient for transforming activity. The homologous wild-type domain, VVG, is
      not required for hormone-regulated signaling.

PMID- 9038377
TI  - Distinct signaling pathways regulate transformation and inhibition of skeletal
      muscle differentiation by oncogenic Ras.
AB  - Expression of oncogenic Ras in 23A2 skeletal myoblasts is sufficient to induce
      both a transformed phenotype and a differentiation-defective phenotype, but the
      signaling pathways activated by oncogenic Ras in these cells and their respective
      contribution to each phenotype have not been explored. In this study, we
      investigated MAP kinase activity in control 23A2 myoblasts and in 23A2 myoblasts
      rendered differentiation-defective by the stable expression of an oncogenic
      (G12V)Ha-ras gene (Ras9 cells). The MAP kinase immunoprecipitated from Ras9 cells
      was 30-40% more active than that from control 23A2 cells. To establish if this
      elevated MAP kinase activity is essential to the maintenance of the oncogenic Ras
      induced phenotype, we utilized the selective MAP kinase kinase 1 (MEK1)
      inhibitor, PD 098059. PD 098059 decreased the MAP kinase activity in Ras9 cells
      to the level found in 23A2 cells. PD 098059 did not affect the ability of 23A2
      myoblasts to differentiate. PD 098059 reverted the transformed morphology of Ras9
      cells but did not restore the ability of these cells to express the muscle
      specific myosin heavy chain gene or to form muscle fibers. Treatment with PD
      098059 also did not affect the ability of oncogenic Ha-Ras to establish a non
      myogenic phenotype in C3H10T1/2 cells co-expressing MyoD. These results
      demonstrate that the activation of MAP kinase is necessary for the transformed
      morphology of Ras9 cells but is not required by oncogenic Ras to establish or to
      maintain a differentiation-defective phenotype. While these data do not rule out
      the possibility that constitutive signaling by MEK1 or MAP kinase could inhibit
      myoblast differentiation, they clearly demonstrate that other pathways activated
      by oncogenic Ras are sufficient to inhibit differentiation.

PMID- 9038378
TI  - Regulation of the urokinase-type plasminogen activator gene by the oncogene Tpr
      Met involves GRB2.
AB  - The oncogene Tpr-Met is a constitutively active form of the hepatocyte growth
      factor/scatter factor (HGF/SF) receptor Met. It comprises the intracellular
      moiety of Met linked to the dimerization domain of the nuclear envelope protein
      Tpr, thus functioning as a constitutively activated Met. HGF/SF is responsible
      for various biological processes including angiogenesis and wound healing, in
      which secreted serine protease urokinase-type plasminogen activator (uPA) is
      implicated. The action of HGF/SF on cells is mediated by the autophosphorylation
      of Met on two carboxyterminal tyrosine residues, Y1349VHVNATVY1356VNV. The two
      tyrosine residues provide docking sites for various effector molecules,
      suggesting that multiple signaling pathways are activated to exert biological
      effects of HGF/SF [Ponzetto et al., Cell (1994) 77: 261]. We found that Tpr-Met
      efficiently activates the uPA gene via a SOS/Ras/extracellular signal regulated
      kinase (ERK)-dependent signaling pathway. Mutation of Y1356, which abrogates GRB2
      binding, reduced the induction to half of the control level, while mutation of
      Y1349 showed little effect on uPA induction, suggesting an important but partly
      replaceable role for GRB2 in Met-dependent uPA gene induction. Mutation of both
      Y1349VHV and Y1356VNV into optimal PI 3-kinase sites resulted in a residual
      induction of about one quarter of the control level, suggesting a potential role
      for PI 3-kinase. Dose-response analysis of the Tpr-Met showed a biphasic curve.
      These results suggest that the interplay among different signaling molecules on
      the receptor is important for full induction of the pathway leading to the
      activation of the uPA gene.

PMID- 9038379
TI  - Expression of a novel isoform of Vav, Vav-T, containing a single Src homology 3
      domain in murine testicular germ cells.
AB  - Vav is a signal transducing molecule containing C-terminal Src homology 3 (SH3)
      SH2-SH3 domains, and has been thought to be expressed exclusively in
      hematopoietic and trophoblastic cells. By Northern blot analysis, vav transcripts
      of unique sizes, 4.8 kb and 1.0 kb, were detected in the testis among various
      tissues examined. From a mouse spermatocyte cDNA library, a novel isoform of vav
      (vav-T) was cloned, which corresponded to a part of the 4.8 kb transcript. Vav-T
      had an alternative 5' sequence up to the middle of SH2-coding region, and encoded
      163 amino acids with a single SH3 domain. Northern blot analysis of fractionated
      testicular cells and in situ hybridization histochemistry demonstrated that vav-T
      transcripts were expressed in the differentiating germ cells, especially
      spermatocytes. A 24 kD protein was detected by anti-Vav antibodies in the testis,
      but not in the spleen or bone marrow. Transcripts of heterogeneous nuclear
      ribonucleoprotein K, known to associate with the most C-terminal SH3 domain of
      Vav, were also detected in the differentiating male germ cells. These results
      demonstrate expression of previously nondescribed Vav-isoform in the testicular
      germ cells, and suggest that it interacts with RNA-binding proteins and plays an
      important role in spermatogenesis.

PMID- 9038380
TI  - Characterization of factor-independent variants derived from TF-1 hematopoietic
      progenitor cells: the role of the Raf/MAP kinase pathway in the anti-apoptotic
      effect of GM-CSF.
AB  - Human hematopoietic progenitor cells (TF-1) undergo apoptosis upon deprivation of
      their dependent cytokine. In this report, we have isolated and characterized some
      spontaneously derived cytokine-independent variants from TF-1 cells. Analysis of
      several signaling molecules known to be activated by the GM-CSF pathway revealed
      that two non-autocrine variants were still responsive to GM-CSF stimulation.
      However, both variants, without ligand stimulation, already had some activated
      forms of Raf and MAP kinases. Given current knowledge, the activated Raf/MAP
      kinase pathway was likely to be responsible for the survival of both variants in
      the cytokine-free medium. However, the growth of hybrids between wild type and
      either variant was unexpectedly dependent on GM-CSF. Both variants like the wild
      type cells were still susceptible to apoptosis induced by other stimuli. These
      results suggest that either the activated Raf/MAP kinase pathway in both variants
      is not sufficient to repress the 'two-fold' death signals generated from the
      hybrids or that there is another mechanism that is responsible for the factor
      independent growth of both variants.

PMID- 9038381
TI  - p53 re-expression inhibits proliferation and restores differentiation of human
      thyroid anaplastic carcinoma cells.
AB  - Alterations of the tumor suppressor gene p53 are uncommon in differentiated
      thyroid neoplasia but are detected at high frequency in anaplastic thyroid
      carcinoma suggesting that impaired p53 function may contribute to the
      undifferentiated and highly aggressive phenotype of these tumors. Effects of wild
      type p53 (wt-p53) re-expression were investigated in a human anaplastic thyroid
      carcinoma cell line (ARO) expressing a mutated p53. ARO cells were stably
      transfected with the temperature-sensitive p53 Val135 gene (ts-p53) which
      exhibits wild type-like activity at 32 degrees C. Exogenous wt-p53 function in
      ARO-tsp53 clones was assessed by evaluating its transcriptional activity on a CAT
      reporter vector containing p53 binding sites. At 32 degrees C, a significant
      reduction in the proliferation rate (approximately or equal to 50%) was observed,
      with accumulation of cells in the G0/G1 phase of the cell cycle. This effect was
      accompanied by induction of the expression of the growth inhibitor p21/Waf1 gene.
      At 32 degrees C, ARO-tsp53 clones also showed a marked impairment of their
      tumorigenic potential. Furthermore, transfected clones re-acquired the ability to
      respond to thyrotropin (TSH) stimulation showing an increased expression of
      thyroid-specific genes (thyroglobulin, thyroperoxidase and TSH receptor). In
      conclusion, re-expression of wt-p53 activity in ARO cells, inhibits cell
      proliferation and restores responsiveness to physiological stimuli.

PMID- 9038382
TI  - Strong indication for a breast cancer susceptibility gene on chromosome 8p12-p22:
      linkage analysis in German breast cancer families.
AB  - Chromosomal losses involving the short arm of chromosome 8 are frequent in a
      variety of tumor types, including breast cancer, suggesting the presence of one
      or more tumor suppressor genes in this region. Previous linkage analysis and
      studies of loss of heterozygosity (LOH) have suggested the presence of a putative
      third breast cancer susceptibility gene around D8S505 at 8p12-p22. We have
      performed linkage analysis in two German breast cancer families, showing negative
      lod scores with 17q and 13q markers, using seven adjacent microsatellite markers
      from 8p12-p22. Incorporating LOH data from tumors of the affected family members
      a maximum cumulative three-point lod score of 3.30 at theta = 0.00 was obtained
      with D8S137 and D8S131. Our findings considerably strengthen the evidence for a
      third breast cancer susceptibility locus (BRCA3) mapping to the short arm of
      human chromosome 8.

PMID- 9038383
TI  - Rat maf related genes: specific expression in chondrocytes, lens and spinal cord.
AB  - maf is a family of oncogenes originally identified from avian oncogenic
      retrovirus, AS42, encoding a nuclear bZip transcription factor. We have isolated
      two maf related cDNA clones, maf-1 and maf-2, from a rat liver cDNA library.
      Comparison of the sequence homologies of the proteins encoded by maf-1 and maf-2
      with those of c-maf and chicken mafB indicated that maf-1 and maf-2 are the rat
      homologues of mafB and c-maf, respectively. Both genes are expressed at low
      levels in a wide variety of rat tissues, including spleen, kidney, muscle and
      liver. Immunohistochemical studies and in situ hybridization analyses show that
      maf-1 and maf-2 are strongly expressed in the late stages of chondrocyte
      development in the femur epiphysis and the rib and limb cartilage of 15 day old
      (E15) embryo in rat. Cartilage cells, induced by subcutaneous implantation of
      bone morphogenic protein, also expressed maf-1 and maf-2. In situ hybridization
      analyses of E15 embryos show that both genes are expressed in the eye lens and
      the spinal cord as well as the cartilage. However, the expression patterns of maf
      1 and maf-2 in lens and spinal cord are different.

PMID- 9038384
TI  - Immunocytomorphopathological studies on the pathogenesis of rheumatoid arthritis.
AB  - Thirty cases of rheumatoid arthritis were submitted to cytomorphological,
      histopathological (HE, VG, PAS Alcian, Gomori, Safranine O), histoenzymological
      (Acid Phosphatase, chondroitin-sulphatase, Peroxidase) and immunological
      (rheumatoid factor (RF)) studies; circulating immune complexes, anti-collagen
      antibodies II, Reactive C protein (CRP), Complementary C3 fraction were also
      assessed. The synoviocytogram of the rheumatoid synovial fluid (SF) indicated a
      cytosis with polynucleosis and ragocytosis compared to the hydroarthrosic SF
      defined by lymphocytosis (47.8%). Enzymologically, especially for high titres of
      rheumatoid factor, a phosphatase and peroxidase activity was observed in
      polymorphonuclear cells of a ragocytary type and in phagocytic mononuclear cells.
      The severe forms of rheumatoid arthritis (RA) were correlated histopathologically
      with chronic villous synovitis associated with some processes of obliterant
      vascularitis, fibrosis and sclerosis. At the level of synovio-cartilage junction,
      fissures and a homogenization of the cartilaginous fundamental substance in the
      vicinity of disintegrated synovial structures were noticed. Histoenzymologically,
      a lysosomal and oxidative activity was found in chondrocytes and in synovial
      macrophages. Immunological assessments (73 serum and 60 synovial fluid samples)
      showed pathological values of circulating immune complexes, anti-collagen
      antibodies and C reactive protein. The complementary synovial depletion of the C3
      fraction underlines the immune character of the rheumatoid synovitis. The
      immunocytomorphologic data correlation demonstrates the involvement of
      immunologic and enzymatic factors in the evolution of Rheumatoid Arthritis.

PMID- 9038385
TI  - The effect of ethanol upon early development in mice and rats. XXIII. The effect
      of indomethacin on beer-induced disturbances of preimplantation development in
      rats.
AB  - The effect of Indomethacin on beer-induced modifications of preimplantation
      development was investigated in rats (control on day 5 of pregnancy), using the
      following criteria: the mean number of embryos/animal, topographical distribution
      of embryos, the developmental stage attained, the appearance of pathological
      forms, the mean cell number/embryo. It resulted that previous administration of
      Indomethacin antagonized the main deleterious effect of repeated acute
      administration of beer in the preimplantation period, supporting the hypothesis
      of prostaglandins (PG) being involved in the pathogenetic action of this
      alcoholic beverage.

PMID- 9038386
TI  - Apoptosis II: Apoptosis in the pathogenesis and treatment of diseases.
AB  - This review presents the implications of abnormal regulation of apoptosis in the
      pathogenesis of a variety of diseases, some of them characterized by a failure of
      cells to undergo apoptosis, and the others characterized by cell loss. The new
      perspectives in the therapy of such diseases by developing therapeutic agents
      that increase or decrease the susceptibility of particular cells to apoptosis are
      also reviewed.

PMID- 9038387
TI  - Meningocerebral lesions in children with iatrogenic AIDS.
AB  - This study is focused on structural modifications of leptomeninges and cerebral
      matter in children deceased because of iatrogenic AIDS. Although we do not
      evidence the specific lesions of AIDS, we have noticed edema, hyperemia, hematic
      extravasation, microlesions of the small vessel walls, perivascular infiltrations
      with lymphocytes, macrophages and even plasmocytes, moderate tigrolysis, mild
      demyelination, gliosis and sidero-calcic deposits. We do not consider these
      lesions as specific to HIV-infected patients.

PMID- 9038388
TI  - Significance of the expression of hormone receptors and of p53 protein in breast
      carcinomas.
AB  - A certain proportion of breast cancers contain hormone receptors--specific
      proteins with high affinity and capacity of selective tie of these hormones.
      There were selected 30 patients presenting breast cancer, treated at the surgical
      departments from the County Hospital of Timisoara between 1993 and 1995. The
      identification of hormone receptors was done on 10% formalin-fixed and paraffin
      embedded tissue specimens. As anti-hormone receptors, monoclonal and polyclonal
      antibodies were used. The immunohistochemical identification of positive to
      hormone receptors cancer cells was obtained, by nucleus staining.
      Immunohistochemical assay of the accumulation of p53 protein seems to be an
      efficient means of selecting breast neoplasms. p53 immunostaining is positive at
      the level of malignant cells' nuclei and negative for normal cells. From the 30
      breast carcinomas, 19 (63.3%) were ER+ and 15 (49.9%) were PR+, resulting an
      increase of the frequency of ER+ tumors together with the age of the patients; 9
      cases (30%) expressed p53 protein, harmonizing with the data in the literature.

PMID- 9038389
TI  - Expression and significance of tumoral suppressor p53 gene in lung
      adenocarcinomas.
AB  - The mutations of p53 tumoral suppressor gene are the most frequent genetic
      modifications identified till now in lung cancer, suggesting that these
      alterations represent critical stages in malignant cellular transformation of
      respiration ways. Conformational changes induced by these mutations are
      associated with stabilisation of the product of p53 gene and the accumulation of
      the mutant protein in malignant cells' nuclei, in quantities that can be
      immunohistochemically detected: immunohistochemistry can be used as an indirect
      indicator of the genome alteration. Eight cases of lung adenocarcinoma were
      immunohistochemically analysed (formalin-fixed and paraffin-embedded specimens),
      in order to find the p53 suppressor expression. The overexpression of p53 protein
      was detected using an antigenous system and Monoclonal Mouse Anti-Human p53
      protein, and it was detected in 5 (62.5%) of the 8 examined adenocarcinomas. In
      the examined cases, p53 overexpression was limited only to neoplastic cells, the
      nuclear staining being considered specific. p53 high level was correlated to:
      histological differentiation degree, smoking, the stage of the tumor and to the
      survival rate of the patients. The association of smoking with p53 overexpression
      suggests that p53 gene is a target of specific mutagenes in smokers.

PMID- 9038390
TI  - Prognostic significance of neuroendocrine differentiation in carcinoma of the
      prostate.
AB  - Biopsies taken by core-needle biopsy and/or transurethral resection to 68
      patients with prostatic neoplasia stage III and IV, were studied
      morphohistochemically. Morphological observations showed high incidence of mixed
      histopathological forms. The Churukian-Schenk and Garvey silver impregnations
      were used in order to identify associated neuroendocrine differentiations. Three
      cases presented monomorphic small cell proliferation which contained numerous
      argyrophilic cytoplasmic granulations. The prognosis in these cases was poor--the
      patients died because of neoplastic extension within 5 to 9 months following
      diagnosis. Neuroendocrine cells were identified in 15 cases, 6 of which presented
      a malignant pattern. Taking into consideration the hormonal resistance of
      malignant cells with argyrophilic granulations, the necessity of chemotherapy
      associated to hormonotherapy is discussed.

PMID- 9038391
TI  - Carcinoid tumor with uterine location. Case report.
AB  - A carcinoid is defined as a tumor arising from endocrine cells with
      neurosecretory characteristics belonging to the APUD system. These cells are most
      frequently observed in the digestive tract and lungs. Uterine location is rare.
      This paper presents the case of a 21-year old patient with uterine carcinoid
      tumor. In order to establish the histopathologic diagnosis of the carcinoid
      tumor, we used optical microscopy examination in haematoxylin-eosin, argentic
      impregnation in Fontana-Masson staining and an immunohistochemical reaction using
      monoclonal antibody to the S100 protein. Due to the intracytoplasmatic
      granulations shown in Fontana-Masson staining and in the immunohistochemical
      reaction to S100 protein which confirm the neurosecretory character of the
      tumoral cells, we included this tumor in the group of tumors with neuroendocrine
      differentiation.

PMID- 9038392
TI  - Some aspects of oxidative metabolism in human endometrium after long time of
      applying the intrauterine contraceptive device.
AB  - The paper intends to study the variation of oxidative metabolism of human
      endometrium (all the components) after applying the intrauterine contraceptive
      device for a long period of time. The results of the study show that
      modifications "in situ" of the oxidative enzymes vary according to the: type of
      the enzymes (NADH2-cytochrome-c-reductase, Lactatdehydrogenase), the hormonal
      cyclic stage (proliferative phase, or luteal phase), epithelial or connective
      tissue structures, time of resting the intrauterine contraceptive device (DIU) in
      uterus.

PMID- 9038393
TI  - Histopathologic aspects in endometrium dysplasias.
AB  - The paper presents a study consisting of 87 cases of endometrial hyperplasias.
      Histopathologic examination allowed us to identify the singular glandulo-cystic
      and adenomatous hyperplasia and the coexistence of the two lesions, but also the
      association (for two cases) of chronic adenomatous hyperplasia to endometrial
      carcinoma. These aspects plead for considering hyperplasia as a precancerous
      lesion taking into account the physiological stage when it appears.

PMID- 9038394
TI  - Intestinal metaplasia and dysplastic modifications in H. pylori gastritis.
AB  - Certain studies regarding modifications of gastric mucosa in the presence of
      infections produced by H. pylori add a new element in the pathology of gastric
      lesions with a high malignancy potential. From the certain premalignant lesions,
      a special place is occupied by intestinal metaplasia and by gastric dysplasia,
      because of their high frequency. This study is based upon the interpretation of
      130 gastric biopsies in which the identification of H. pylori was pursued (by HE
      staining, Giemsa), o intestinal metaplasia and their types (by PAS-Blue Alcian ph
      2.5 staining and High Iron Diamine-Blue Alcian ph 2.5) and the presence of
      neoplastic lesions. Particular aspects of our study are given by the association
      of H. pylori infection with certain types of intestinal metaplasia, with moderate
      or severe dysplastic lesions and with gastric carcinomas (especially the
      "intestinal" type).

PMID- 9038395
TI  - Clinical value of Helicobacter pylori identification by histochemical methods in
      patients with chronic gastritis.
AB  - There were studied 68 patients admitted with clinical signs of chronic gastritis.
      Biopsies were taken by endoscopical route from the antral and fundic levels in
      all cases, and paraffin slides were stained with haematoxylin-eosine, modified
      Giemsa, Warthin-Starry and blue cresyl methods. Microscopical results were
      compared with those obtained with the urease test performed from the gastric
      mucus. Results noted the presence of Helicobacter pylori in 41 from 68 cases in
      the antral mucosa, like curved bacteria located in the mucus on the excretory
      segment and often on the surface, covering the epithelium. Intracellular
      Helicobacter pylori was not noted. Its presence is related especially with the
      active chronic gastritis and rarely with inactive forms; it was not possible to
      establish a relationship between the morphology, incidence and features of their
      infiltrate, and the presence of Helicobacter pylori. The modified Giemsa method
      is easier to perform, faster and cheaper, and it may be currently applied in
      practice, but from the sensitivity viewpoint, best results have been achieved
      with Warthin-Starry silver impregnation.

PMID- 9038396
TI  - Study on the normal and pathologic structures of the hard dental tissues using
      the scanning electron microscope.
AB  - The recent use in biology of the Scanning Electron Microscope allows a new vision
      of the sample, completing the previous ones: the Optical Microscope (OM) and the
      Conventional Electron Microscope--CEM. The object is observed in space, in a
      direct way and, due to a system of variable sizes, the passage from a general
      image to the detailed tissue and cell study is permitted. The outer enamel
      surface with its perikymaties, its flaws and its changes caused by usage as well
      as by the internal enamel structure on the fractured area have been studied. On
      the occlusal surface of the decayed teeth, focal holes have been found; they
      resulted probably from creation disturbances due to some amelogenetic disorders
      that damage the ameloblast, matrix creation or its mineralization. These lacunar
      flaws are the favourite zones for the microbe plate accumulation and propitious
      to carious lesions initiation. The same clinical aspect, of profound enamel
      creation defects with an anfractuous crevass network aspect, having a variable
      expansion and depth, can be found in microscope with some healthy teeth.
      Regrouping in fascicles of the different prism directions can be found after
      structural analysis of the prismatic morphology of the parodontotic tooth enamel.
      An aspect of a more compact structure is thus obtained sectionally. This explains
      partially the increased resistance to decay of these teeth. In a comparative
      study of the fractioned area of some decayed and ruined temporary teeth,
      significant differences in prism arrangement can be found. The decayed teeth show
      expansions of the intraprismatic spaces, accusing reduced resistance against
      decay attack.

PMID- 9038397
TI  - [Characterization of topogenic sequences which regulate the integration and
      membrane topology of proteins in the endoplasmic reticulum membrane].

PMID- 9038398
TI  - [Regulation of cytoskeleton and cell adhesion by small GTPases].

PMID- 9038399
TI  - [Molecular mechanism of tissue-specific actions of oestrogen].

PMID- 9038400
TI  - [Translational control through nonsense suppression].

PMID- 9038401
TI  - [Autophagy in yeast, bulk protein degradation in the vacuole].

PMID- 9038402
TI  - [Recent advances in glycobiology on KDN-containing glycoconjugates].

PMID- 9038403
TI  - Audiovisual links in exogenous covert spatial orienting.
AB  - Subjects judged the elevation (up vs. down, regardless of laterality) of
      peripheral auditory or visual targets, following uninformative cues on either
      side with an intermediate elevation. Judgements were better for targets on either
      modality when preceded by an uninformative auditory cue on the side of the
      target. Experiment 2 ruled out nonattentional accounts for these spatial cuing
      effects. Experiment 3 found that visual cues affected elevation judgments for
      visual but not auditory targets. Experiment 4 confirmed that the effect on visual
      targets was attentional. In Experiment 5, visual cues produced spatial cuing when
      targets were always auditory, but saccades toward the cue may have been
      responsible. No such visual-to-auditory cuing effects were found in Experiment 6
      when saccades were prevented, though they were present when eye movements were
      not monitored. These results suggest a one-way cross-modal dependence in
      exogenous covert orienting whereby audition influences vision, but not vice
      versa. Possible reasons for this asymmetry are discussed in terms of the
      representation of space within the brain.

PMID- 9038404
TI  - Separate influences of orientation and lighting in the inverted-face effect.
AB  - Studies of the inverted-face effect typically use photos as stimuli. Inverting
      photos not only misorients the face but also reverses important shading and
      shadow cues. We decoupled the influence of spatial orientation and the direction
      of lighting in three experiments and found that the relation between these
      factors varied with the task given to observers. When the task required
      identification of faces (Experiments 1 and 3), the factors were additive,
      consistent with a strategy of mental rotation of the face prior to an
      interpretation of the shading cues. When faces were assigned to coarse categories
      (Experiments 2 and 3), these factors interacted, consistent with a more piecemeal
      approach to face processing. We propose that the identification of a specific
      individual depends on configurational information, which is preserved if the
      image of an inverted face is mentally rotated before the identification process
      is begun.

PMID- 9038405
TI  - Judging the time to collision with a simulated textured object: effect of
      mismatching rate of expansion of object size and of texture element size.
AB  - We measured the accuracy with which subjects estimated the time to collision with
      a simulated textured object approaching at constant speed along the line of
      sight. The independent variable was the ratio R, where R = (rate of dilation of
      the texture elements that covered the simulated object)/ (rate of dilation of
      object size). When matching was perfect (i.e., R = 1.0), the mean of 12 settings
      was close to the nominal value of 2,000 msec for the 2 subjects. In addition, the
      standard error of 12 settings was only 25 and 52 msec in 2,000 msec for the 2
      subjects. Discrimination threshold for time to collision was not significantly
      affected by R over the range investigated between R = 0 and R = 2.0. However, the
      accuracy of estimating time to collision was significantly affected by R.
      Estimated time to collision was a monotonic function of R. For example, when the
      mismatch was only 10% (i.e., R = 0.9) subjects judged time to collision would
      occur 178 msec later than the true time to collision of 2,000 msec.

PMID- 9038406
TI  - Haptic discrimination of bilateral symmetry in 2-dimensional and 3-dimensional
      unfamiliar displays.
AB  - In five experiments, we tested the accuracy and sensitivity of the haptic system
      in detecting bilateral symmetry of raised-line shapes (Experiments 1 and 2) and
      unfamiliar 3-D objects (Experiments 3-5) under different time constraints and
      different modes of exploration. Touch was moderately accurate for detecting this
      property in raised displays. Experiment 1 showed that asymmetric judgments were
      systematically more accurate than were symmetric judgements with scanning by one
      finger. Experiments 2 confirmed the results of Experiment 1 but also showed that
      bimanual exploration facilitated processing of symmetric shapes without improving
      asymmetric detections. Bimanual exploration of 3-D objects was very accurate and
      significantly facilitated processing of symmetric objects under different time
      constraints (Experiment 3). Unimanual exploration did not differ from bimanual
      exploration (Experiment 4), but restricting hand movements to one enclosure
      reduced performance significantly (Experiment 5). Spatial reference information,
      signal detection measures, and hand movements in processing bilateral symmetry by
      touch are discussed.

PMID- 9038407
TI  - The perception of biological motion across apertures.
AB  - To understand the visual analysis of biological motion, subjects viewed dynamic,
      stick figure renditions of a walker, car, or scissors through apertures. As a
      result of the aperture problem, the motion of each visible edge was ambiguous.
      Subjects readily identified the human figure but were unable to identify the car
      or scissors through invisible apertures. Recognition was orientation specific and
      robust across a range of stimulus durations, and it benefited from limb
      orientation cues. The results support the theory that the visual system performs
      spatially global analyses to interpret biological logical motion displays.

PMID- 9038408
TI  - Velocity-dependent improvements in single-dot direction discrimination.
AB  - Thirty-six Brown University students participated in three experiments designed
      to address perceptual learning. In each experiment, visual discrimination
      thresholds were tracked over 4,200 trials. Results from Experiment 1 suggest that
      the pattern of threshold reduction on a single-dot motion-direction
      discrimination task was stimulus direction specific and matched (in a velocity
      dependent manner) the threshold reduction pattern previously reported for a line
      orientation discrimination task. In Experiment 2, it was determined that the
      stationary-line-orientation-specific practice effects originally reported by
      Vogels and Orban (1985) could be replicated but were contingent on line length.
      Similarly, the results from Experiment 3 suggest that practice effects originally
      reported by Ball and Sekuler (1987) could be replicated but were contingent on
      stimulus velocity. Implications for the mechanisms underlying direction and
      orientation discrimination are considered.

PMID- 9038409
TI  - Cultural and linguistic factors in audiovisual speech processing: the McGurk
      effect in Chinese subjects.
AB  - The "McGurk effect" demonstrates that visual (lip-read) information is used
      during speech perception even when it is discrepant with auditory information.
      While this has been established as a robust effect in subjects from Western
      cultures, our own earlier results had suggested that Japanese subjects use visual
      information much less than American subjects do (Sekiyama & Tohkura, 1993). The
      present study examined whether Chinese subjects would also show a reduced McGurk
      effect due to their cultural similarities with the Japanese. The subjects were 14
      native speakers of Chinese living in Japan. Stimuli consisted of 10 syllable
      (/ba/, /pa/, /ma/, /wa/, /da/, /ta/, /na/, /ga/, /ka/, /ra/) pronounced by two
      speakers, one Japanese and one American. Each auditory syllable was dubbed onto
      every, visual syllable within one speaker, resulting in 100 audiovisual stimuli
      in each language. The subjects' main task was to report what they thought they
      had heard while looking at and listening to the speaker while the stimuli were
      being uttered. Compared with previous results obtained with American subjects,
      the Chinese subjects showed a weaker McGurk effect. The results also showed that
      the magnitude of the McGurk effect depends on the length of time the Chinese
      subjects had lived in Japan. Factors that foster and alter the Chinese subjects'
      reliance on auditory information are discussed.

PMID- 9038410
TI  - Time decay of auditory stream biasing.
AB  - In an experiment designed to investigate the time decay of auditory stream
      biasing (ASB), subjects were required to listen to a 10-sec induction sequence of
      repeated tones (AAAA...) designed to bias the listener's percept toward hearing
      an A stream. The induction sequence was followed immediately by a silent interval
      (0-8 sec), and then a short ABAB ... test sequence. To measure the amount of ASB
      remaining at the end of the silent interval, subjects were asked to indicate
      whether the test sequence was temporally coherent or had segregated into separate
      A and B streams. A plot of the mean number of segregation responses against
      silent-interval duration indicated that the overall time decay of ASB can be
      ascribed by an exponential decay function with a time constant of tau = 3.84 sec,
      with musicians having a longer time constant (tau = 7.84 sec) than nonmusicians
      (tau = 1.42 sec). The length of the time constants for musicians and nonmusicians
      suggests that the mechanism responsible for ASB is associated with long auditory
      storage and that future experiments investigating auditory streaming phenomena
      should use interstimulus intervals of at least 8 sec.

PMID- 9038411
TI  - Perceptual grouping in space and time: evidence from the Ternus display.
AB  - We report three experiments investigating the effect of perceptual grouping on
      the appearance of a bistable apparent-motion (Ternus) display. Subjects viewed a
      Ternus display embedded in an array of context elements that could potentially
      group with the Ternus elements. In contrast to several previous findings, we
      found that grouping influenced apparent motion perception. In Experiment 1,
      apparent motion perception was significantly affected via grouping by shape
      similarity, even when the visible persistence of the elements was controlled. In
      Experiment 2, elements perceived as moving without context were perceived as
      stationary without context were perceived as moving when grouped with moving
      elements perceived as stationary without context were perceived as moving when
      grouped with moving context elements. We argue that grouping in the spatial and
      temporal domains interact to yield perceptual experience of apparent-motion
      displays.

PMID- 9038412
TI  - Role of verbal encoding in short- and long-term odor recognition.
AB  - The role of verbal encoding in odor recognition memory was investigated using
      odors of low familiarity to subjects before the experiment began. The
      experimental procedure included two phases--odor learning (first phase) and odor
      memory testing (second phase)--separated by a delay of 7 days. Five experimental
      conditions were established: three conditions of odor learning with names
      (labeling conditions), one condition of odor learning without names (sensory
      familiarization), and one condition of no learning prior to testing (control
      conditions). The labeling conditions differed from each other regarding label
      characteristics. The names were those of odor sources (veridical names), those
      personally generated by subjects (generated names), or those derived from the
      chemical names of the odorants (chemical names). Subjects were required to learn
      20 fixed associations between odors (targets or distractors) and 20 names during
      two daily sessions. The learning sessions included two identification tests and
      ended by a verbal memory test in which subjects recalled odor names. The odor
      memory test was split into two parts separated by a retention interval of either
      20 min (short-term memory) or 24 h (long-term memory). Data showed that olfactory
      recognition memory was enhanced in subjects who associated veridical or generated
      names to odors during the learning session. Chemical names were not appropriate
      to facilitate odor recognition. Similarly, the level of odor identification was
      higher for veridical and generated names than for chemical names, though the
      level of verbal memory for chemical names was substantial. Recognition response
      latencies were systematically longer for a target odor implying a positive
      response than for a distractor odor implying a negative response. Together, these
      data suggest that odor recognition and identification are sensitive to the
      semantic content of labels associated with odors. Odor memory was adversively
      influenced by time, but this influence was less pronounced when the names were
      endowed with a rich semantic content.

PMID- 9038413
TI  - Effects of surface texture and grip force on the discrimination of hand-held
      loads.
AB  - In this paper, we report the results from two experiments in which subjects were
      required to discriminate horizontal load forces applied to a manipulandum held
      with a precision grip. The roughness (and hence friction) of the grip surfaces
      and required grip force were manipulated. In the first experiment, subjects were
      instructed to judge the load while maintaining hand position and not letting the
      manipulandum slip. It was found that performance was influenced by surface
      texture; a given load was judged to be greater when the surface texture was
      smooth than when it was rough. This result is consistent with a previous study
      based on lifting objects and indicates that the effect of surface texture applies
      to loads in general and not just to gravitational loads (i.e., weight). To test
      whether the load acting on a smooth object is judged to be greater because the
      grip force required to prevent it from slipping is larger, a second experiment
      was carried out. Subjects used a visual feedback display to maintain the same
      grip force for smooth and rough manipulandum surfaces. In this case, there was no
      effect of surface texture on load perception. These results provide evidence that
      perceived load depends on the grip force used to resist the load. The
      implications of these results in terms of central and peripheral factors
      underlying load discrimination are considered.

PMID- 9038414
TI  - Tactile learning is task specific but transfers between fingers.
AB  - Practice-related improvement in visual perception is highly specific for
      properties of the stimulus used in training. We explored the specificity of such
      perceptual learning in the human tactile system, using gratings consisting of
      alternating ridges and groves. Practice effects on grating discrimination showed
      limited transfer between grating sets defined by spatial variation in either
      groove width or ridge width, consistent with partially overlapping neural
      representations of these two spatial parameters. In contrast, substantial
      interdigital transfer of practice effects occurred for discrimination of gratings
      varying in either spatial parameter and also for spatial acuity-dependent
      discrimination of grating orientation. We conclude that tactile learning,
      although quite as task specific as in other sensory systems, generalizes with
      considerable facility across fingers, unlike visual learning, which is highly
      location specific.

PMID- 9038415
TI  - Contingent color aftereffects: reassessing old conclusions.
AB  - Although there is considerable evidence supporting an associative interpretation
      of contingent color aftereffects, there are data that appear inconsistent with
      this interpretation. New findings from seven experiments are presented indicating
      that, contrary to earlier claims, contingent color aftereffects are observed
      after induction with (1) single orthogonal black bars on colored backgrounds, (2)
      geometric forms, and (3) two orthogonal grids of the same color. The results of
      these experiments are relevant to an associative interpretation of contingent
      color aftereffects, as well as to assessing alternative interpretations of the
      phenomenon.

PMID- 9038416
TI  - Time course of perceptual grouping.
AB  - An investigation was made of the time course of perceptual grouping that is based
      on two qualitatively different spatial relationships: proximity and alignment. An
      index of grouping capacity was used to assess the processing time required before
      a backward pattern mask interfered with grouping. Stimuli consisted of bistable
      arrays of disjunct dots that were followed by a mask. Grouping cues, either
      proximity or alignment, were randomly assigned to either the horizontal or
      vertical orientation, and subjects indicated whether the dots appeared grouped as
      a series of horizontal or vertical lines. Spatial metrics of the cues were
      systematically altered until they no longer served as a cue for grouping thereby
      determining the grouping threshold. The stimulus onset asynchrony (SOA) of the
      mask, relative to the test stimulus, ranged from 33.3 to 150 msec. The SOA at
      which grouping thresholds first became elevated identified the point at which the
      mask first interfered with the grouping process, thereby identifying the
      processing time required for grouping by the specified cue. The processing time
      for grouping by proximity and alignment differed significantly, requiring means
      of 87.6 and 118.8 msec, respectively, for processing to be completed. These
      measurements serve to identify the processing time necessary for spatially
      integrating stimulus elements into unified forms, thereby delineating temporal
      constraints at this stage of visual processing.

PMID- 9038417
TI  - Adaptation to altered visual-vestibular feedback: mechanisms of maintenance and
      recovery.
AB  - Adaptation of perceived movement during head motion (apparent concomitant motion,
      ACM) and the subsequent elimination of adaptation were studied in two
      experiments. During the adaptation phase of both experiments, subjects performed
      voluntary 1-Hz head oscillations for 6 min while fixating a stimulus moving
      either in the same (with) direction as or the opposite (against) direction of
      head movements. In Experiment 1, ACM adaptation was measured following either a 1
      or a 4-min delay after the adaptation phase. Results indicated some loss of
      adaptation during the additional 3-min delay, demonstrating a tendency of the
      system linking head and image to return to its preadaptation state following
      removal of an adaptation stimulus. In Experiment 2, subjects viewed a stimulus
      after adaptation that appeared to move minimally in the same manner as the
      adaptation stimulus during 3 min of head oscillations. No loss of adaptation was
      measured in these subjects between the beginning and the end of the 3-min
      interval. In another condition, subjects viewed a stimulus that appeared to move
      alternately in the same direction as and in the opposite direction of the
      adaptation stimulus during a similar 3-min interval following adaptation. ACM
      adaptation was substantially reduced during this 3-min interval. These results
      implicate two mechanisms that operate to either maintain or eliminate the short
      term adaptation. One is passive and operates in the absence of visual feedback to
      eliminate the short-term adapted state, and the other responds to postadaptation
      visual feedback.

PMID- 9038418
TI  - Chemotactic peptide analogues. Centrally constrained chemotactic N
      formyltripeptides: synthesis, conformation, and activity of two new analogues.
AB  - The role exercised by the central residue of the chemotactic N-formyltripeptide
      HCO-Met-Leu-Phe-OMe (fMLP-OMe) in controlling both the backbone conformation and
      the biochemical activity is the subject of recent interest. Here, two new
      centrally constrained fMLP-OMe analogues, namely HCO-Met-azaPro-Phe-OMe (4) and
      HCO-Met-(gamma-lactam)-Phe-OMe (6) have been synthesized and their CDCI3 solution
      conformation and activity have been studied. The azapeptide 4 adopts beta-folded
      conformation with the azaPro residue at the i+2 position and an intramolecular H
      bond involving the formylic oxygen and the Phe NH. The gamma-lactam tripeptide 6
      prefers a semi-extended backbone conformation. When tested on human neutrophils
      both the new models were found practically devoid of biological activity. The
      role exerted by the NH groups as well as by the conformational preferences is
      discussed.

PMID- 9038419
TI  - On the concept of a bivalent pharmacophore for SKCa channel blockers: synthesis,
      pharmacological testing, and radioligand binding studies on mono-, bis-, and tris
      quinolinium compounds.
AB  - The dissociation equilibrium constants (Kd values) of dequalinium (2) and the
      monoquinolinium compounds 1a and 1b have been determined from competition
      equilibrium radioligand binding with [125I]apamin on rat brain synaptic plasma
      membranes (SPMs). Dequalinium binds to the channel with 2 orders of magnitude
      higher affinity than 1a or 1b, suggesting that both quinolinium groups are needed
      for potent and selective SKCa channel blockade. The trisquinolinium compound 3
      (1,1'-[5-[4-(4- aminoquinolinium-1-yl)but-1-yl]non-4-en-1,9-diyl]-bis-(4-
      aminoquinolinium)) has been synthesized and tested for inhibition of the
      afterhyperpolarization of rat sympathetic neurones and on the binding assay.
      Compound 3 shows approximately one order of magnitude higher potency than 2,
      being the most potent non-peptidic SKCa channel blocker reported so far (Kd
      approximately 30 nM). The higher affinity of 3 compared with 2 may be due to
      direct binding of the third quinolinium group to the channel or may arise from a
      reduction of the unfavorable entropy of binding via an increase of the "local
      concentration" of quinolinium groups.

PMID- 9038420
TI  - Structure-activity relationship studies of novel pyrazolo[1,5
      c][1,3]benzoxazines: synthesis and benzodiazepine receptor affinity.
AB  - Some 2-arylpyrazolo[1,5-c][1,3]benzoxazin-5-ones 1 and 5- oxopyrazolo[1,5
      c][1,3]benzoxazin-2-carboxylates 2 were prepared and biologically evaluated for
      their binding at benzodiazepine receptor (BZR) in rat cortical membranes.
      Structure-activity relationship studies suggest that, although proton donor d and
      proton acceptor a1 are both optional pharmacophoric descriptors, at least one of
      them must be present for good BZR affinity. When the proton donor d is not
      present, the heteroatom acceptor a1 is necessary either in the tricyclic core or
      in the appended substituent at the C-2 to obtain sub-micromolar BZR affinity.

PMID- 9038421
TI  - New NO-donors with antithrombotic and vasodilating activities, Part 16. 3-Amino
      1,2,4-oxadiazol-5-ones as prodrugs for hydroxyguanidines.
AB  - Nineteen 4-substituted 1,2,4-oxadiazol-5-ones (6a-s) were prepared as prodrugs
      for lipophilic hydroxyguanidines which should be metabolized in vivo to nitric
      oxide. This hypothesis was tested indirectly by measuring the antithrombotic
      properties of these compounds 2 h after oral administration to rats (60 mg/kg).
      In mesenteric arterioles seven compounds moderately (> or = 10%) inhibited the
      formation of thrombi by a laser beam. Maximum effects were observed in 6c (4
      pentyl) and 6f (4-benzyl). The lack of activity in the corresponding 2
      pentyloxadiazolone 10c, where no formation of nitric oxide seems possible,
      indirectly suggests that the antithrombotic properties of the title compounds
      could be mediated by the in vivo formation of nitric oxide.

PMID- 9038422
TI  - Chemistry of indoles carrying a basic function, Part 3. Synthesis of
      spiro[cyclopropane-1,3'[3H]indol]-2'(1'H)-ones with antihypoxic effects.
AB  - Hydroxyindolones (1-6, 15-16) were transformed into isatinylidenes (7, 9-13, 17
      19) by dehydration with 4-toluenesulfonic acid. The dimer-type compounds (14, 20)
      were also isolated in a few cases. The obtained isatinylidenes were transformed
      into 3-spiro-cyclopropane-oxindoles (21-32) with dimethyloxosulfonium methylide.
      Compound 22 shows protective effects against hypobaric hypoxia and triethyltin
      induced brain edema.

PMID- 9038423
TI  - Dibenz[b,f]azepines, Part 7. Synthesis of new, potentially CNS active
      dibenz[b,f]azepine derivatives.
AB  - Reactions of 5-carboxamido-5H-dibenz[b,f]azepines (1a-1d) with glyoxylic acid
      methylester methyl hemiacetal (GMHA) led to 5-(carboxamido-N-alpha-hydroxy-acetic
      acid methyl ester)-5H- dibenz[b,f]azepines (2a-2d). The reactions with glycols
      yielded the oligoethylene glycol derivatives (3,4). The new compounds were
      screened as anticonvulsants and/or antidepressants (AD).

PMID- 9038424
TI  - 3-Hydroxymethylphenytoin valproic acid ester, a new prodrug combining two
      anticonvulsant drugs.
AB  - 3-Hydroxymethylphenytoin valproic acid ester (VAL-PHT) was designed as a new
      prodrug combining valproic acid and phenytoin, two anticonvulsant drugs with
      different pharmacological profiles. The compound was hydrolyzed by rat plasma
      esterases in vitro but exhibited only activity in the maximal electroshock
      seizure test (MES test) after intraperitoneal administration to mice. The
      compound did not protect against pentylenetetrazole-induced seizures. It is
      concluded that VAL-PHT acts as a prodrug displaying the anticonvulsant profile of
      phenytoin.

PMID- 9038425
TI  - Clinical and magnetic resonance imaging changes correlate in a clinical trial
      monitoring cyclosporine therapy for multiple sclerosis. The MS Study Group.
AB  - Magnetic resonance imaging (MRI) was used to monitor cyclosporine therapy for
      chronic progressive multiple sclerosis in a multicenter clinical trial and an
      analysis was performed to determine whether there was a correlation between
      clinical changes and MRI changes. MRI was performed on 163 patients at the onset
      and completion of the 2-year study. Burden of disease (BOD, lesion load) was
      quantitated by a single observer using a computer program. Active lesions were
      also identified. The Expanded Disability Status Scale (EDSS) score was determined
      every 3 months MRI data did not show any effect of cyclosporine treatment on BOD
      progression (mean 24.5% increase/yr) or lesion activity. However, there was a
      statistically significant positive correlation between the baseline total BOD
      value and the baseline EDSS score (r = 0.221, p = 0.005) and a positive
      correlation between the percent changes in BOD from baseline to exit and EDSS
      score (r = 0.186, p = 0.018). The study supports the concepts that MRI is a
      useful technique in monitoring therapeutic trials and that MRI is a direct
      measure of pathology.

PMID- 9038426
TI  - Indications for differential diagnosis of nontumor central nervous system
      diseases from tumors. A positron emission tomography study.
AB  - To accurately differentiate nontumor central nervous system (CNS) diseases from
      brain tumors, we retrospectively evaluated the cerebral circulation and
      metabolism in patients with nontumor CNS diseases using positron emission
      tomography (PET). Regional cerebral blood flow (rCBF), cerebral blood volume
      (rCBV), oxygen extraction fraction (rOEF), the metabolic rates of oxygen
      (rCMRO2), and of glucose (rCMRGI), and the uptake of 11C-methyl-L-methionine (11C
      Met) were visually evaluated in lesions and compared with values for the
      contralateral white matter regions. PET findings were correlated with those of x
      ray computed tomography (CT) and magnetic resonance imaging (MRI), and were
      analyzed for nontumor CNS diseases and cerebral gliomas. rCBF and rCBV were
      changeable from disease to disease or from stage to stage of disease progression.
      rOEF and rCMRO2 remained low in 5 and 6, respectively, of 9 nontumor CNS diseases
      examined, whereas these parameters were increased in CNS infections such as brain
      abscess. Overall, noteworthy was the locally increased rOEF and rCMRO2 in the
      patients with a brain abscess in contrast to the values for patients with
      gliomas. rCMRGI reflected biological characteristics of each disease, and
      correlated with cell density, whether reactive glial cells or inflammatory cells.
      11C-Met was accumulated at a certain stage of nontumor CNS diseases, which
      implied uptake of the tracer as a result of disruption of the blood-brain barrier
      as well as metabolic incorporation.

PMID- 9038427
TI  - Neuroimaging findings in Rasmussen's syndrome.
AB  - Rasmussen's syndrome is a progressive childhood disease of unknown cause
      characterized by severe epilepsy, hemiparesis, mental deterioration, inflammation
      of one cerebral hemisphere, and brain atrophy. Computed tomography, single-photon
      emission computed tomography (SPECT), and magnetic resonance (MR) neuroimaging
      findings of 8 patients with pathologically confirmed Rasmussen's syndrome were
      evaluated retrospectively. All patients showed a predominance of the atrophy in
      the temporoinsular region and cerebral hemispheric alterations on MR images in a
      similar extension as seen on SPECT studies. Focal increase in regional cerebral
      blood flow was observed in the 4 patients presenting with epilepsia partialis
      continua at the time of hexamethylpropyleneamineoxime injection. Extensive
      cortical hypoperfusion was noted in the other 4 patients who received the
      injection during the interictal state. Cerebellar functional abnormalities were
      present in 6 patients, 2 of them with structural damage.

PMID- 9038428
TI  - Ultrasonographic assessment of the prevalence of fasciculations in lesions of the
      peripheral nervous system.
AB  - In previous studies, ultrasonography was a very sensitive method in detecting
      fasciculations. The present study was intended to examine the prevalence of
      ultrasonographically visible fasciculations in patients with neuromuscular
      diseases affecting the lower extremities. Ultrasonography of 9 muscles (rectus
      femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius,
      semitendinosus, tibialis anterior, gastrocnemius, and soleus muscles) was
      performed bilaterally in 70 adult healthy subjects and 172 patients with various
      neuromuscular diseases. Fasciculations were detected in 109 (63%) of 172
      patients. The median value of affected muscles was 10 (range 1-18). Patients with
      spinal muscular atrophy (37/38, p < 0.001), hereditary motor and sensory
      neuropathy (24/25, p < 0.001), and lumbosacral radiculopathy with motor deficits
      (24/29, p < 0.001) exhibited fasciculations more frequently than did healthy
      volunteers. Radiculopathy with sensory deficits, lesions of either plexus or
      peripheral nerves, compartment syndrome, and myopathy were not associated with a
      significantly enhanced prevalence of fasciculations in the patient group compared
      to the control group. In summary, fasciculations are a frequent ultrasonographic
      sign in neuromuscular diseases. They are almost regularly found in patients with
      spinal muscular atrophy and those with hereditary motor and sensory neuropathy.
      Thus, the absence of fasciculations in ultrasonographic assessment should give
      cause for reconsidering these diagnoses.

PMID- 9038429
TI  - Risk factors differ for carotid artery plaque with and without acoustic
      shadowing. Atherosclerosis Risk in Communities Study Investigators.
AB  - To investigate the association of gender, ethnicity, and several cardiovascular
      risk factors with carotid artery plaque and plaque with acoustic shadowing in a
      population-based sample, high-resolution B-mode ultrasonography was used to
      characterize lesions in the common and internal carotid arteries, and at the
      carotid bifurcation in 12,796 US men and women, aged 45 to 64 years,
      participating in the Atherosclerosis Risk in Communities Study (ARIC) baseline
      survey. In multiple logistic regression analyses, male gender (odds ratio and 95%
      confidence interval: 1.52 [1.39-1.67]) and increased total (1.47 [1.32-1.63]) and
      low-density-lipoprotein cholesterol (1.49 [1.34-1.65]) levels were statistically
      significantly associated only with the presence of plaque. In contradistinction,
      smoking (2.22 [1.79-2.75]) and hypertension (1.54 [1.30-1.82]) were additionally
      associated with acoustic shadowing. Hyperfibrinogenemia (1.33 [1.12-1.59]) was
      associated only with lesions accompanied by acoustic shadowing. While ethnicity
      associations with plaque alone varied across the artery segments, among those
      with plaque, being white was uniformly associated with acoustic shadowing. After
      multivariable adjustment, high-density-lipoprotein cholesterol was not associated
      with either manifestation of atherosclerosis. In conclusion, differences were
      seen in the associations of established cardiovascular risk factors with
      discretely characterized carotid artery plaque lesions, according to the presence
      or absence of acoustic shadowing suggestive of mineralization of plaque.

PMID- 9038430
TI  - Visualization of the cerebral circulation using three-dimensional transcranial
      power Doppler ultrasound imaging.
AB  - The purpose of this study was to evaluate the anatomy of the cerebral
      circulation, particularly the circle of Willis, using three-dimensional
      ultrasound (3DUS) imaging. Image data were obtained through the right
      transtemporal window from 8 young, healthy volunteers by acquiring gray-scale and
      color Doppler spectral (CDI) and energy (CDE) images using two-dimensional
      ultrasound equipment with a 2-MHz probe. Images and transducer position
      coordinates were fed into a graphics workstation, reprojected, analyzed to
      extract the blood flow signal, volume rendered, and displayed interactively. The
      architecture of the cerebral circulation was evaluated from multiple orientations
      using stereo viewing glasses and rotation to enhance the understanding of vessel
      position. The primary vessels of the cerebral circulation including the circle of
      Willis and bilateral views of the branching arteries (middle, anterior, and
      posterior cerebral arteries and internal carotid artery) could be imaged readily
      with 3DUS through one transtemporal window. Acquisition time was typically less
      than 30 seconds. Volume-rendering methods greatly assisted in showing the overall
      spatial relationships and continuity of cranial vessels. Secondary branches of
      the cerebral arteries were seen in 2 patients. Color data from two-dimensional
      ultrasound imaging that otherwise might be identified as artifact was found to
      represent continuous small vessels on three-dimensional viewing. 3DUS facilitates
      imaging of cranial vascular anatomy by clarifying overall spatial relationships
      and enhancing comprehension, compared to two-dimensional ultrasound methods. The
      method is rapid and the circle of Willis can be visualized from one side of the
      head.

PMID- 9038431
TI  - Three-dimensional ultrasound angiography (power mode) for the quantification of
      carotid artery atherosclerosis.
AB  - Three-dimensional (3D) ultrasound angiography was performed to diagnose carotid
      artery atherosclerosis. Thirty-five patients (15 women, 20 men) with a history of
      cerebrovascular disease were examined using conventional color-coded Doppler
      ultrasound and 3D ultrasound angiography. Carotid stenosis was initially
      diagnosed using continuous-wave Doppler ultrasound. To determine intraobserver
      and interobserver reliabilities, 21 patients were evaluated using 3D ultrasound
      on three occasions. Sixty-five percent of patients were diagnosed with stenosis
      of more than 50%. Twenty-two percent of plaques had a smooth surface, 72.9% were
      ulcerated, and 5.1% were indeterminate. Data collection for 3D imaging required 5
      minutes per patient, whereas image processing and plaque volume quantification
      required 30 minutes. Plaque volume ranged from 0.053 to 0.685 ml. The
      intraobserver and interobserver variabilities were 4.16 and 5.87%, respectively
      (r = 0.96, p < 0.0001; r = 0.89, p < 0.0001). 3D Color Doppler and 3D ultrasound
      angiography assessments of plaque volume differed by 8.5%. Plaques were more
      precisely differentiated using 3D ultrasound, and plaque volume quantification
      was less affected by echo shadowing after 3D reconstruction. In comparison to
      other techniques for the quantification of atherosclerotic lesions. 3D ultrasound
      angiography offers a more precise quantitative method for prospective, clinical
      studies of atherosclerosis.

PMID- 9038432
TI  - Optic chiasmal compression by venous aneurysm: magnetic resonance imaging
      diagnosis.
AB  - The overwhelming majority of traumatic carotid cavernous fistulas present with a
      bruit, arterialization of conjunctival vessels, or an elevated intraocular
      pressure. Described herein is a patient who presented with progressive
      deterioration of vision, without any of the above signs. Magnetic resonance
      imaging demonstrated compression of the optic ch asm by a venous aneurysm arising
      from a carotid cavernous fistula. This entity should be considered in patients
      who present with progressive visual loss.

PMID- 9038433
TI  - Successful surgical removal of an asymptomatic optic nerve hemangioblastoma in
      von Hippel-Lindau disease.
AB  - An asymptomatic patient with a family history of von Hippel-Lindau disease
      carried the abnormal gene for this disease. An imaging survey that consisted of
      computed tomography, magnetic resonance imaging, and cerebral angiography
      revealed an optic nerve hemangioblastoma. The potential for visual loss in the
      future was the indication for microsurgical intervention. This was the first
      asymptomatic optic nerve hemangioblastoma to be imaged and the first to be
      successfully removed without any permanent neurological deficits or vision loss.

PMID- 9038435
TI  - Shoot first, draw later peroneal nerve palsy: a sonographic study.
AB  - A 32-year-old man had an unusual gunshot wound to the leg, causing a peroneal
      nerve palsy. Sonography provided useful complementary findings to the
      electrodiagnostic localization of the injury.

PMID- 9038434
TI  - Clinical and diagnostic findings in a patient with Creutzfeldt-Jakob disease
      (type Heidenhain).
AB  - A 61-year-old woman had Creutzfeldt-Jakob disease, type Heidenhain, that
      progressed for 4 months until death, 3 of which she spent in a hospital. The
      diagnosis was verified by autopsy. Consecutive brain computed tomography,
      magnetic resonance imaging, blood flow measurements, electroencephalography
      (EEG), and routine laboratory tests were performed. All imaging techniques showed
      nonspecific pathological changes, whereas EEG revealed alterations indicative for
      Creutzfeldt-Jakob disease.

PMID- 9038436
TI  - 150 years of ether anaesthesia and what is next?

PMID- 9038437
TI  - Economics of low-flow anaesthesia in children.
AB  - We have measured the consumption of isoflurane and fresh gas flows in 77 infants
      and children during 20 all-day operating sessions using either the enclosed
      Mapleson A or the circle absorber mode of the Carden 'Ventmasta' ventilator. The
      average consumption (SD) of isoflurane in 37 patients anaesthetised using the A
      mode of the Carden system with a mean fresh gas flow of 2.61 min-1 was 11.1 (4.2)
      g.h-1, while that in 40 patients anaesthetised using the circle absorber mode
      with a mean fresh gas flow of 1.21 min-1 was 4.7 (1.0) g.h-1. These figures
      represent an overall saving of 58% in the use of isoflurane (p < 0.0001) and a
      mean reduction in fresh gas flow of 54% (p < 0.0001) as a result of using low
      flow anaesthesia. With the addition of small bore breathing hoses the adult
      circle absorber system was practical to use in both infants and children. These
      findings should stimulate interest in the use of low-flow techniques in children.

PMID- 9038438
TI  - Audit of postoperative pain control. Influence of a dedicated acute pain nurse.
AB  - The inadequacies of conventional intramuscular opioid analgesia have fueled an
      expansion in the use of patient-controlled analgesia and epidural analgesia after
      surgery. This is not always accompanied by increased education and specialist
      supervision of ward staff and patients. A survey in our hospital prior to the
      appointment of an Acute Pain Nurse showed an unacceptable incidence of side
      effects when epidural analgesia was employed on ordinary surgical wards. More
      surprisingly, efficacy of patient-controlled analgesia was found to be low.
      Frequent review of patients and regular education of ward staff by a specialist
      Pain Nurse have achieved a substantial reduction in side effects of epidural
      analgesia and improvement in efficacy of patient-controlled analgesia. We have
      shown that the advantages of patient-controlled analgesia can be largely negated
      by failure to address deficiencies in knowledge of pain management among ward
      staff and patients.

PMID- 9038440
TI  - Effect of epidural block on the lag time of pulse oximeter response.
AB  - Thirty-six healthy patients, ASA 1, aged 16-41 years, scheduled for elective
      plastic surgery were studied to determine if thoracocervical or lumbar epidural
      blocks affected the lag time of the pulse oximeter response. Patients were
      allocated to receive thoracocervical epidural block (n = 20) (group 1)
      (lignocaine 1%) or lumbar epidural block (n = 16) (group 2) (lignocaine 1.5%).
      Epidural block was performed with a 17-gauge Tuohy needle inserted in the midline
      between C7-T2 vertebrae in group 1 and between L1-S1 in group 2 and an epidural
      catheter was introduced. Arterial oxygen saturation (SpO2) was measured
      continuously using a Datex pulse oximeter. The lag time of the pulse oximeter
      response was measured while breathing oxygen (100%) after breath-holding. Values
      were obtained 10 min before and 5, 10, 15, 20, 30, and 40 min after epidural
      injection of a test dose. There was a progressive decrease in the lag time of the
      pulse oximeter response so that by 30 min after epidural injection the mean (SD)
      value had decreased from 29 (6.1) to 14 (3.4) in Group 1 and 41 (12.8) to 23
      (7.9) s in group 2 (p < 0.01).

PMID- 9038439
TI  - Pretreatment with controlled-release morphine for pain after hysterectomy.
AB  - In a double-blind randomised study, two dosing regimens for controlled-release
      morphine tablets were compared against placebo to ascertain the extent of
      prophylactic postoperative pain control in 51 women undergoing abdominal
      hysterectomy. One group of patients received controlled-release morphine every 12
      h for 2 days before surgery, a second group received a single dose of controlled
      release morphine 2 h before surgery and a third group received placebo. Patient
      controlled analgesia system demands were compared for the first 38 h after
      surgery and 10-point pain scores and McGill pain questionnaires were compared for
      the first 6 postoperative days and at 6 weeks after surgery. During the first 2
      days after surgery, patients reported high levels of pain which were similar in
      all groups. Pain scores on the third and fourth postoperative days were
      significantly lower in those who had a single pre-operative dose of controlled
      release morphine compared with placebo and those who had been treated with
      morphine every 12 h for 2 days (p = 0.043 and 0.024 for third and fourth day
      respectively). Patient-controlled analgesia demands were also fewer and less
      variable in those patients receiving the single dose of morphine 2 h before
      surgery. The study shows a beneficial analgesic effect of a single pre-operative
      dose of morphine, but shows no benefit for a more prolonged pre-operative dosing
      regimen.

PMID- 9038441
TI  - Intra-ocular pressure changes during gynaecological laparoscopy.
AB  - Laparoscopic surgery carried out under general anaesthesia is associated with
      physiological changes, which also determine changes in intra-ocular pressure. We
      measured intra-ocular pressure at each phase of gynaecological laparoscopy,
      carried out under propofol-alfentanil-isoflurane general anaesthesia, in young
      women of ASA 1 status, with no pre-existing eye disease. Measurements were made
      with a Perkins applanation tonometer. Mean arterial pressure and end-tidal CO2
      tension were kept constant throughout the study. Intra-ocular pressure decreased
      significantly after induction of anaesthesia, remained unchanged after a
      pneumoperitoneum of up to an intraperitoneal pressure of 15 mmHg had been
      created, increased significantly with head down tilt, but did not increase
      significantly above pre-induction values. Adequate depth of anaesthesia
      compensated for the intra-ocular pressure increase caused by head down position.
      Plateau airway pressure, considered as reflecting intrathoracic pressure,
      increased with intraperitoneal pressure elevation. However, such changes did not
      correlate with intra-ocular pressure changes.

PMID- 9038442
TI  - Venous levels of lignocaine and bupivacaine after peribulbar block.
AB  - Twenty-five patients undergoing elective cataract day surgery were studied after
      receiving a dual-injection peribulbar block with a mixture consisting of equal
      volumes of 2% lignocaine and 0.75% bupivacaine with hyaluronidase. A maximum of
      10 ml of solution was used for the initial block; supplementary injections of up
      to 10 ml were given to five patients. Venous blood was taken prior to the block
      and then 1, 10, 20, 30, 60 and 90 min after the block. The peak mean
      concentrations of lignocaine (0.722 microgram.ml-1) and bupivacaine (0.353
      microgram.ml-1) were found at 10-20 min after injection when no top-up was given
      and at 10 min after the top-up injection when required. All measured serum
      concentrations of lignocaine and bupivacaine were below the accepted toxic levels
      of the two drugs. However, the highest individual toxicity score after a top-up
      was 0.915 which was very close to the toxicity threshold (= 1) when a scoring
      system was used to assess the combined levels.

PMID- 9038443
TI  - Blood flow in the lower limbs in the knee-chest position. Ultrasonographic study
      in unanaesthetised volunteers.
AB  - The knee-chest position for lumbar spine surgery is favoured because decreased
      filling of the epidural veins is associated with reduced peroperative bleeding.
      However, the position may be unfavourable from a circulatory point of view. In
      the present study, non-invasive assessment of circulation in the lower limbs was
      performed in 21 unanaesthetised, healthy volunteers who were placed in the
      surgical knee-chest position. Measurements included blood flow velocity (colour
      Doppler ultrasonography), oscillotonometric arterial blood pressure from upper
      and lower limbs and pulse oximetry from a toe. There was a statistically
      significant reduction in the posterior tibial artery flow velocity, maximally
      31.6%, when the subject was moved from the prone to the knee-chest position. An
      enlargement of the trunk-femoral angle at the hip did not improve arterial flow.
      In 10 of the 21 volunteers, no flow in the posterior tibial vein was detected in
      the knee-chest position. In spite of the deteriorated blood flow, pulse oximetry
      indicated sufficient capillary flow in the very periphery of the lower limb. The
      change from prone to knee-chest position resulted in an increase in arterial
      blood pressure of the upper limb; the increase in diastolic arterial pressure was
      statistically significant (p < 0.001). It is concluded that the surgical knee
      chest position involves deterioration of both the arterial and venous flow of the
      lower limbs. This should be considered in patients undergoing surgery in this
      position and, in particular, in those at risk of developing cardiovascular
      complications.

PMID- 9038444
TI  - Gas leakage and the laryngeal mask airway. A comparison with the tracheal tube
      and facemask during spontaneous ventilation using a circle breathing system.
AB  - The ability of the laryngeal mask airway, tracheal tube and facemask to provide a
      leak free seal in a clinical setting was assessed by measuring the minimal fresh
      gas flows needed in a closed circle system during spontaneous ventilation on 60
      subjects. The fresh gas flow was reduced until no spillage occurred from the pop
      off valve. This fresh gas flow was taken to represent the sum of gas uptake by
      the subject and gas leakage from the circuit. The median fresh gas flow after 20
      minutes was 350 ml.min-1 in the laryngeal mask airway group, 350 ml.min-1 in the
      tracheal tube group and 450 ml.min-1 in the facemask group. The fresh gas flow
      required for the facemask group was significantly higher than that for the
      laryngeal mask airway or tracheal tube groups (p < 0.01). There was no
      significant difference between the fresh gas flows required for the tracheal tube
      and laryngeal mask airway group. We conclude that the laryngeal mask airway
      provides as good a gas tight seal as a tracheal tube in this context and would be
      of benefit in reducing anaesthetic gas pollution.

PMID- 9038445
TI  - Respiratory effects of spinal anaesthesia for caesarean section.
AB  - We report the changes observed in a number of pulmonary function tests performed
      on 36 patients undergoing Caesarean section under spinal anaesthesia. The tests
      comprised peak expiratory flow, forced expiratory volume in one second, forced
      vital capacity, forced expiratory volume in one second to forced vital capacity
      ratio and the maximal mid-expiratory flow. Significant changes occurred that are
      consistent with a restrictive ventilatory defect. These changes persisted for
      four hours after the induction of spinal anaesthesia. Administration of 35%
      oxygen by facemask failed to change significantly fetal umbilical vein pH or
      partial pressure of oxygen.

PMID- 9038446
TI  - A ventilation-exchange bougie for fibreoptic intubations with the laryngeal mask
      airway.
AB  - The ventilation-exchange bougie is a new airway device which can be mounted on a
      fibreoptic laryngoscope for passage through the larynx into the trachea via a
      laryngeal mask airway. Subsequent removal of the fibreoptic laryngoscope and
      laryngeal mask airway allows a tracheal tube to be railroaded into position over
      the ventilation-exchange bougie. This study described the use of this technique
      for elective tracheal intubation in two groups of 12 subjects in whom difficulty
      with intubation was not expected. All the subjects were successfully intubated by
      one of two anaesthetists, one experienced and the other inexperienced with
      fibreoptic intubation techniques. Neither had had prior experience with the
      ventilation-exchange bougie. Because ventilation was maintained throughout the
      procedure, intubation did not need to be hurried. Cusum analysis confirmed the
      impression of a learning curve and the technique could be considered learnt after
      four and six intubations for the experienced and inexperienced fibreoptic
      laryngoscopists respectively. No difficulty was found either in intubating the
      larynx with the fibreoptic laryngoscope and ventilation-exchange bougie or when
      railroading the tracheal tube over the ventilation-exchange bougie. It is
      suggested that this new device could have an important role in teaching
      fibreoptic techniques, management of the difficult airway and failed intubations.

PMID- 9038447
TI  - A laboratory assessment of oxygen delivery from a portable chemical generator.
AB  - A simple portable chemical oxygen generator was tested in the laboratory. The
      device is designed for use by the public as an oxygen supply until an emergency
      team arrives with appropriate oxygen cylinders. The generator was found to supply
      a mean (SD) flow of oxygen of 3.6 (0.01) l.min-1 for 12.5 (range 12.4-12.6)min.
      The mean (SD) total volume of oxygen produced was 47(0.17) l. The supplied oxygen
      mask was a variable performance type with the problems and limitations inherent
      in this design; an oxygen flow of 8 l.min-1 is required to provide 40% oxygen and
      most of the oxygen is wasted and not available to the patient. This poses a
      serious limitation to any device which has a limited capability (in flow and/or
      total volume) for producing oxygen.

PMID- 9038448
TI  - Use of a neonatal noninvasive blood pressure module on adult patients.
AB  - A clinical and statistical comparison of systolic, mean and diastolic arterial
      blood pressures was made between a non-invasive technique using a neonatal
      oscillometric blood pressure monitor attached to the thumb versus an invasive
      technique using a catheter inserted into the ipsilateral radial artery in 18
      patients undergoing general anaesthesia for major surgery. In 1258 readings, the
      mean differences between the pressures obtained (invasive versus non-invasive)
      were +9.1, -7.9, and -0.7 mmHg for systolic, diastolic and mean pressures
      respectively. Oscillometric blood pressure measurement using the thumb appears to
      be an acceptable method for monitoring blood pressure during anaesthesia and has
      advantages over conventional cuff placement on the upper arm.

PMID- 9038449
TI  - Pruritus--itching for a cause and relief?
AB  - The mechanisms of pruritus, an unpleasant irritation on the skin that provokes an
      urge to scratch, are reviewed. Whilst symptomatic treatment is only partially
      effective, antihistamines remain the first choice of treatment. However, recent
      novel treatment using opiate antagonists, propofol (subhypnotic doses) and
      serotonin antagonists offer attractive alternatives.

PMID- 9038450
TI  - Hypotension, subarachnoid block and the elderly patient.
AB  - This article reviews the current literature on the management of hypotension
      during subarachnoid block in the elderly. Hypotension results from blockade of
      the sympathetic nervous system, which causes decreases in both systemic vascular
      resistance and cardiac output. Abolition of normal cardiovascular reflexes is
      also important and may explain unexpected cardiac arrests during subarachnoid
      block. Untreated block in the elderly results in decreases in systolic arterial
      pressure, systemic vascular resistance and central venous pressure. Cardiac
      output appears not to decrease as has been previously reported and heart rate is
      affected by several different factors. Preload to the heart should be maintained
      during block by giving adequate intravenous fluids and 8 ml.kg-1 is satisfactory
      in most cases. Adequate preloading prevents decreases in cardiac output and
      unexpected cardiac arrests. In this respect, mild head down till is also
      beneficial. Ideally, intravenous fluid should be given as the block is
      developing. Excessive fluid administration serves no useful purpose and can cause
      fluid overload and urinary retention. If systolic arterial pressure decreases by
      more than 25%, or to below 90 mmHg, treatment with a vasopressor is indicated.
      The efficacy of ephedrine has recently been questioned, as it is a poor
      vasoconstrictor and inotrope in the elderly. The alpha-adrenoceptor agonists may
      prove a more logical choice, because they increase both peripheral resistance and
      preload. Metaraminol by infusion (< 10 ml.h-1 of 10 mg in 20 ml) has been used
      successfully, though hypertension can occur.

PMID- 9038451
TI  - Sciatic nerve palsy following childbirth.
AB  - Two cases are reported of sciatic nerve palsy after delivery by Caesarean section
      in primigravidae. One mother was slender and had an emergency Caesarean section
      for failure to progress with a breech presentation. Epidural analgesia during
      labour was extended for operative delivery. The other mother was obese, mildly
      hypertensive, had a large baby with a high head and was delivered by elective
      Caesarean section under epidural anaesthesia. She experienced severe intrapartum
      hypotension. Both patients suffered right sided sciatic nerve palsy. The
      aetiologies of obstetric palsies and those following regional block are reviewed
      and the importance of careful diagnosis and of avoiding peripheral nerve
      compression during regional block are emphasised.

PMID- 9038452
TI  - Asystole from tetanic stimulation of the accessory nerve.
AB  - An asystolic cardiac arrest is reported which occurred at the same time as
      supramaximal tetanic stimulation over the accessory nerve in order to evoke
      contractions in the trapezius and sternocleidomastoid muscles. The cause may have
      been the inadvertent stimulation of one or more of the cranial nerves of the
      carotid sheath at the base of the skull: the cranial root of the accessory nerve,
      the vagus, the sino-carotid branch of the glossopharyngeal nerve or the
      hypoglossal nerve. The most likely culprit, if not the vagus itself, was the
      cranial root of the accessory nerve which both functionally and anatomically
      should be seen as an integral part of the vagus. It is suggested that stimulation
      of any nerve in the carotid sheath should be approached with caution and that a
      tetanic stimulus to this area might best be avoided.

PMID- 9038453
TI  - Epidural anaesthesia, ephedrine and phenylephrine in a patient taking
      moclobemide, a new monoamine oxidase inhibitor.
AB  - We report a case of low thoracic epidural and general anaesthesia in a patient
      receiving moclobemide, a new selective inhibitor of monoamine oxidase A. Intra
      operative hypotension was initially treated with phenylephrine and then with
      ephedrine. The short half-life of moclobemide and its modest interaction with
      direct and indirect acting sympathomimetic drugs permit the use of epidural
      anaesthesia, since any associated hypotension can be safely treated.

PMID- 9038454
TI  - Acquired laryngomalacia as a cause of airway obstruction immediately after
      unilateral mouth floor surgery.
AB  - We report a case of acquired laryngomalacia in which airway obstruction due to
      prolapse of the epiglottis during inspiration was observed immediately after a
      unilateral mouth floor resection. Suggested causes are resection of unilateral
      elevator muscles of the hyoid bone, epiglottic oedema and transient loss of
      pharyngeal motor control due to surgical intervention and high-dose radiation.

PMID- 9038455
TI  - Leg ischaemia in an infant following accidental intra-arterial administration of
      atracurium treated with caudal anaesthesia.
AB  - We describe the effects of accidental intra-arterial injection of suxamethonium
      and atracurium into the femoral artery of an infant. An 11-month-old boy with
      Downs Syndrome and obstructive sleep apnoea presented for tonsillectomy.
      Peripheral venous cannulation proved impossible. A femoral venous line was sited
      following inhalational induction of anaesthesia. Suxamethonium was given through
      this line and produced no adverse effect. Subsequently, atracurium was given
      through the line causing an instant cutaneous flush in the leg followed by a
      marked ischaemic appearance. The femoral line was assumed to be sited in the
      femoral artery and was removed. At the end of the operation a caudal injection of
      10 ml of 0.25% bupivacaine was performed. Within 30 min there was marked
      vasodilation of both legs with easily felt peripheral pulses. In view of the
      tonsillectomy anticoagulant and thrombolytic therapy were contra-indicated. There
      were no adverse sequelae.

PMID- 9038456
TI  - Lithium toxicity.
AB  - We report a case of severe lithium toxicity precipitated by a thiazide diuretic
      and compounded by an angiotensin converting enzyme inhibitor. There was severe
      vasodilatation refractory to noradrenaline.

PMID- 9038457
TI  - Spinal anaesthesia and spina-bifida occulta.
AB  - We describe a patient with unexpected spina bifida who underwent spinal
      anaesthesia for trans-urethral resection of prostate and developed serious
      neurological signs. An unexpected spinal tumour was removed two weeks later. This
      report demonstrates that not all neurological problems associated with spinal
      anaesthesia should be blamed on the technique.

PMID- 9038458
TI  - Tissue expander causing iatrogenic difficult intubation.
AB  - Difficulty during tracheal intubation may occur due to a number of anatomical
      factors and pathological conditions. These factors may be influenced by earlier
      surgical manoeuvres, so that difficulty may occasionally be encountered at
      subsequent operation. One such case of 'iatrogenic' difficulty, where a tissue
      expander beneath the anterolateral skin of the neck caused transient intubation
      problems, is reported.

PMID- 9038459
TI  - A comparison of prophylactic ondansetron and metoclopramide administration in
      patients undergoing major neurosurgical procedures.
AB  - In a prospective, randomised, double-blind trial, we assessed the relative
      efficacy of prophylactic ondansetron and metoclopramide administration in the
      reduction of postoperative nausea and vomiting in 60 patients undergoing routine
      major neurosurgical procedures. The patients were randomly allocated into one of
      two groups. Both groups received a standardised anaesthetic. When the dura mater
      was closed, patients in group A received an intravenous injection of
      metoclopramide 10 mg whilst group B received ondansetron 8 mg intravenously.
      Patients who received metoclopramide experienced less postoperative nausea and
      vomiting than those who received ondansetron in the 48 h following surgery (17
      (56%) versus 9 (30%) p = 0.038). In the light of these findings, we believe that
      ondansetron is an inappropriate agent for the prevention of postoperative nausea
      and vomiting in the neurosurgical population.

PMID- 9038460
TI  - The incidence of post dural puncture headache in children.
AB  - One hundred and five children with malignant disease attended for lumbar puncture
      which was performed under general anaesthesia. A questionnaire was answered over
      the next three days to determine the incidence of post dural puncture headache
      Ninety-seven questionnaires were returned and the results show that no child aged
      under ten years developed a headache. Of the children aged 10-12 years, two out
      of seventeen developed a headache (11.8%). In children aged 13-18 years, five out
      of ten developed a headache (50%).

PMID- 9038461
TI  - Jaw thrusting as a clinical test to assess the adequate depth of anaesthesia for
      insertion of the laryngeal mask.
AB  - We have studied the efficacy of the loss of response to jaw thrust as a clinical
      test to assess adequate depth of anaesthesia for insertion of the laryngeal mask
      in 60 patients. After induction of anaesthesia with propofol (infused using a
      syringe driver), the patients were randomly allocated to one of two groups. In
      one group, insertion of the laryngeal mask was attempted immediately after the
      loss of verbal contact and in the other group, after the loss of motor response
      to a jaw thrust. Conditions for insertion of the laryngeal mask were assessed.
      The mean dose of propofol required to obtain loss of verbal contact was 1.94
      mg.kg-1 (SD 0.39, 95% confidence intervals (CI) 1.79-2.08 mg.kg-1) and that for
      the loss of response to jaw thrust was 2.55 mg.kg-1 (SD 0.46, 95% CI 2.38-2.72
      mg.kg-1). When depth of anaesthesia was assessed using jaw thrusting, it was
      always possible to insert the mask and the conditions were optimal in 87% (95% CI
      72-95%) of patients. Neither coughing nor gagging occurred. In contrast,
      conditions were almost always less than optimal when insertion was attempted
      after the loss of verbal contact. Conditions were significantly better when jaw
      thrust was used as a clinical test compared with loss of verbal contact (p < <
      0.001). No marked haemodynamic depression occurred in any patient. Thus, jaw
      thrust is a reliable clinical test to assess the adequate depth of anaesthesia
      for uncomplicated insertion of the laryngeal mask after induction of anaesthesia
      with propofol.

PMID- 9038462
TI  - The optimal dose of ketamine for caudal epidural blockade in children.
AB  - Sixty boys aged up to 9 years undergoing orchidopexy were randomly allocated to
      receive one of three solutions for caudal epidural injection: group A received 1
      ml.kg-1 of 0.25% bupivacaine with 0.25 mg.kg-1 of preservative-free ketamine,
      group B received 1 ml.kg-1 of 0.25% bupivacaine with ketamine 0.5 mg.kg-1 and
      group C received 1 ml.kg-1 of 0.25% bupivacaine with 1 mg.kg-1 of ketamine.
      Postoperative pain was assessed by means of a modified Objective Pain Score and
      analgesia was administered if this score exceeded four. The median duration of
      caudal analgesia was 7.9 h in group A, 11 h in group B and 16.5 h in group C.
      There were no differences between the groups in the incidence of motor block,
      urinary retention, postoperative vomiting or postoperative sedation. Group C had
      a significantly higher incidence of behavioural side effects, including slightly
      odd behaviour, vacant stares and abnormal effect than groups A and B.

PMID- 9038463
TI  - The effect of glycopyrrolate on postoperative pain and analgesic requirements
      following laparoscopic sterilisation.
AB  - In order to evaluate the contribution of tubal spasm to pelvic pain following
      laparoscopic sterilisation, we have studied the effect of glycopyrrolate, an
      anticholinergic agent with antispasmodic properties, on 60 ASA 1 and 2 patients
      presenting as day-cases for laparoscopic sterilisation using Filshie clips. In a
      randomised, double-blind, controlled trial, patients received either
      glycopyrrolate 0.3 mg or saline intravenously prior to induction of anaesthesia.
      Compared with the control group, patients receiving glycopyrrolate had
      significantly reduced immediate postoperative pain scores (p < 0.02) and required
      significantly less postoperative morphine (p < 0.01). Nausea, vomiting and anti
      emetic requirements were also reduced though not significantly. We conclude that
      glycopyrrolate 0.3 mg at induction of anaesthesia is an effective method of
      improving the quality of recovery after day-case laparoscopic sterilisation using
      clips.

PMID- 9038464
TI  - Pain following craniotomy: a preliminary study comparing PCA morphine with
      intramuscular codeine phosphate.
AB  - We have performed a prospective randomised trial of 30 patients undergoing
      craniotomy to compare intramuscular codeine phosphate with patient-controlled
      analgesia using morphine 1 mg bolus with a 10-min lockout and no background
      infusion. For 24 h postoperatively, pain, nausea, Glasgow coma score, respiratory
      rate and sedation score were assessed. There was a wide variation in the amounts
      of morphine requested by the patients in the patient-controlled analgesia group
      in the first 24 h postoperatively (range 2-79 mg, median 17 mg). There was a
      small, but non-significant, reduction in pain scores in the patient-controlled
      analgesia group. There were no significant differences between the two groups in
      respect of nausea and vomiting, sedation score or respiratory rate. No major
      adverse effects were noted in either group. Patient-controlled analgesia with
      morphine is an alternative to intramuscular codeine phosphate in neurosurgical
      patients which merits further investigation.

PMID- 9038466
TI  - Ethics in obstetric anaesthesia.

PMID- 9038465
TI  - Pre-operative oral administration of morphine in day-case gynaecological
      laparoscopy.
AB  - The analgesic effect of morphine sulphate 10 mg by mouth given pre-operatively on
      pain after gynaecological laparoscopy was studied in a randomised, prospective,
      double-blind, placebo-controlled comparison. Two groups of 56 patients were
      studied one group undergoing diagnostic laparoscopy and the other laparoscopic
      sterilisation. All patients received a standard anaesthetic after premedication
      with morphine or placebo 1 h before the operation. Morphine premedication did not
      significantly influence postoperative pain as assessed on a visual analogue scale
      in either group and postoperative opioid consumption was unaffected.
      Premedication with morphine 10 mg orally does not significantly decrease pain
      after day-case gynaecological laparoscopy.

PMID- 9038467
TI  - Ethics in obstetric anaesthesia.

PMID- 9038468
TI  - Ethics in obstetric anaesthesia.

PMID- 9038469
TI  - Classification of caesarean section.

PMID- 9038470
TI  - Classification of caesarean sections.

PMID- 9038471
TI  - Postponing patients with pre-operative hypertension.

PMID- 9038472
TI  - Colour coded drug packaging.

PMID- 9038473
TI  - Pre-oxygenation, hyperoxygenation and lung aeration.

PMID- 9038474
TI  - Tourniquet technique for axillary block.

PMID- 9038475
TI  - Optimum LMA cuff pressure.

PMID- 9038476
TI  - Topical lignocaine for laryngeal mask airway insertion.

PMID- 9038477
TI  - The laryngeal mask airway as an adjunct to extubation on the intensive care unit.

PMID- 9038478
TI  - Burns caused by ECG monitoring during MRI imaging.

PMID- 9038479
TI  - Personnel and facilities for electroconvulsive therapy.

PMID- 9038480
TI  - Epidural morphine and postherpetic neuralgia.

PMID- 9038481
TI  - A method of identifying the caudal space--a 'scratch' test.

PMID- 9038482
TI  - Retrospective versus contemporaneous nausea scores.

PMID- 9038483
TI  - Local or general anaesthesia for cataract surgery.

PMID- 9038484
TI  - Anaesthesia for cardioversion in children.

PMID- 9038485
TI  - Anaesthesia for cardioversion.

PMID- 9038486
TI  - Use of the 'AeroChamber' during induction of anaesthesia.

PMID- 9038487
TI  - Vein graft surveillance: is the case proven?

PMID- 9038488
TI  - Psychological factors in postoperative adjustment to stoma surgery.
AB  - Around one-quarter of stoma patients experience clinically significant
      psychological symptoms post-operatively. Psychological disorders are often not
      detected by those involved with the care of stoma patients. Past psychiatric
      history, dissatisfaction with preoperative preparation for surgery, postoperative
      physical symptomatology and the presence of negative stoma-related
      thoughts/beliefs have all been shown to be significantly associated with
      psychological morbidity after surgery. These findings suggest that healthcare
      professionals (especially surgeons involved with this patient population) should
      ask all patients about these factors before and after surgery. Questionnaires
      could be used to screen for difficulties and/or staff could undertake training
      aimed at improving the detection of psychological morbidity and endeavour to
      strengthen links with liaison mental health services. Future research in this
      area should be prospective, using psychometrically valid measures and be focused
      on the prediction, prevention, detection and treatment of poor psychological
      adjustment after stoma surgery.

PMID- 9038489
TI  - Radiological confirmation of intraperitoneal free gas.
AB  - Although subdiaphragmatic gas on an erect chest or abdominal radiograph usually
      indicates the presence of a gastrointestinal perforation, this sign is present in
      only 60-80% of cases. Other less well known radiographic signs of perforation
      that may nonetheless be of utmost importance in diagnosis are described. The
      presence of such signs may then prompt further diagnostic procedures or surgical
      intervention as appropriate.

PMID- 9038490
TI  - Clinical xenotransplantation: past, present and future.
AB  - The ability to use animal organs, such as from the pig, for the purposes of
      transplantation in humans, would clearly overcome the major shortage of human
      organs that greatly restricts transplantation programmes worldwide. Recent
      experimental advances have raised the possibility of renewed attempts at organ
      xenotransplantation in humans within the near future. Previous clinical
      experience, dating back to 1906, is briefly reviewed. The problems that still
      require resolution include the immunological barrier, the risk of transferring
      infectious agents with the transplanted organ, and uncertainty as to whether the
      transplanted animal organ will function satisfactorily in the human environment.
      Ironically, the answers to some of these problems may only be provided when
      clinical xenotransplantation is undertaken.

PMID- 9038491
TI  - Control mechanisms in bone resorption: 240 years after John Hunter.

PMID- 9038492
TI  - The role of mandibular condylar cartilage in articular cartilage repair.
AB  - The articular hyaline cartilage of synovial joints has a very limited capacity
      for repair after injury. In contrast, the mandibular condylar cartilage of the
      temporomandibular joint possesses as intrinsic potential for regeneration. This
      study aimed to test the hypothesis that cultured allografts of mandibular
      condylar cartilage could be used to promote biological repair of injured
      orthotopic joint surfaces. Using a primate animal model, cultures of mandibular
      condylar cartilage cells were grafted into surgically created defects in a
      recipient hyaline cartilage joint surface. Articular wound healing was assessed
      macroscopically and histologically over a postoperative period of 52 weeks.
      Mandibular condylar cartilage cells scheduled for allogenous transplantation were
      initially characterised in vitro. Expansion of primary colonies in organ culture
      provided the allogenic cellular material for in vivo grafting. Grafting of
      osteochondral articular wounds with 5-week cultures of mandibular cartilage cells
      led to wound regeneration with complete reconstitution of articular surface
      continuity by 52 weeks. There was novel synthesis of cartilage collagens and
      sulphated glycosaminoglycans within the repair tissue and no evidence of
      immunological rejection. Healing of grafted defects was thought to occur by a
      combination of donor cell proliferation and ingress of host mesenchymal cells. In
      contrast, grafted control wounds underwent largely fibrous repair with incomplete
      articular regeneration. In conclusion, transplanted allografts of cultured
      mandibular condylar cartilage appeared to have the ability, in this primate
      model, to promote cartilaginous repair and regeneration of orthotopic articular
      wounds.

PMID- 9038493
TI  - Lower gastrointestinal bleeding during anticoagulant therapy: a life-saving
      complication?
AB  - Warfarin is commonly used in the prophylaxis or treatment of thromboembolic
      disease. Haemorrhage is a recognised complication which may be life-threatening.
      This paper describes eight cases in which lower gastrointestinal bleeding while
      on warfarin therapy resulted in the discovery of previously unrecognised large
      bowel malignancy. Diagnosis of an otherwise asymptomatic carcinoma in this way
      enabled surgery to be carried out at an earlier stage and so may have resulted in
      a better prognosis for these patients. Bleeding while on anticoagulant therapy is
      caused by a specific organic lesion in 30% to 50% of cases. This may be the case
      even when the prothrombin time is very prolonged. It is important, therefore,
      that such cases are fully investigated, especially in the elderly.

PMID- 9038494
TI  - Quality of life in patients undergoing inguinal hernia repair.
AB  - Inguinal hernia repair is one of the most common surgical procedures undertaken
      in the NHS. Despite this, no previous work has examined quality of life in this
      patient group. This study examines quality of life preoperatively and at 3 and 6
      months postoperatively in 140 patients undergoing inguinal hernia repair in the
      context of a randomised controlled trial of laparoscopic versus open hernia
      repair. Surgery was undertaken on a day case basis, and quality of life was
      assessed using the Short Form 36 (SF36). In the initial phase of the study, 57%
      of those screened for suitability met the study inclusion criteria and were
      randomised. No significant differences were found between laparoscopic and open
      hernia repair in terms of quality of life at 3 and 6 months postoperatively. No
      difference was found between 3 and 6 month scores, suggesting that patients had
      already made a good recovery by 3 months. A significant improvement was found
      between preoperative and postoperative scores, with the greatest change arising
      on dimensions assessing pain, physical function, and role limitation owing to
      physical restriction. After standardising for age, sex, and social class, a
      comparison of the hernia patients to population norms for the SF36 was consistent
      with improvement from preoperative to postoperative assessment. This study has
      demonstrated the improvement in quality of life in patients undergoing elective
      inguinal hernia repair by experienced surgeons on a day case basis. It has also
      demonstrated the feasibility of assessing quality of life using generic measures
      in this patient group. Further work in this area is required. Ultimately, the
      priority given to elective inguinal hernia repair will depend on how the
      demonstrated benefits compare with those derived from other elective surgical
      procedures.

PMID- 9038495
TI  - Does hospital mortality rate reflect quality of care on a surgical unit?
AB  - All deaths occurring in 1 year in the surgical unit of a district general
      hospital were analysed to determine to what extent crude mortality rates reflect
      the quality of care. There were 166 deaths, 70% of patients were aged 75 years
      and older, and 87.3% were emergency admissions. Almost one-half (46.4%) of the
      deaths were inevitable. This high proportion of inevitable deaths means that
      crude hospital mortality rates are a poor indicator of the quality of surgical
      care. Factors such as the nature of the catchment area served, the proportion of
      emergency versus elective admissions, the numbers of complex operations performed
      and the availability of convalescent or hospice facilities are a greater
      influence on surgical mortality rates than variations in the standard of surgical
      care. The use of crude hospital mortality rates to compare the quality of care
      given by surgical units should be discontinued as it is unreliable and
      misleading.

PMID- 9038496
TI  - Preconditioning the human heart.
AB  - The phenomenon of ischaemic preconditioning protects the myocardium by limiting
      infarct size in animal models of ischaemia and reperfusion. Ischaemic
      preconditioning may be induced by short periods of ischaemia and reperfusion. We
      investigated whether the human heart can be ischaemically preconditioned during
      coronary artery bypass grafting (CABG). Patients were enrolled into two separate
      studies. In the first study myocardial adenosine triphosphate (ATP) was used as
      the measured endpoint, assayed from myocardial biopsies taken at onset of
      cardiopulmonary bypass (CPB), at the end of the preconditioning stimulus, and at
      the end of a 10 min sustained ischaemic insult. In the second study the release
      of myocardial troponin T was used as the endpoint; taken at pre-CPB, and at 1, 6,
      24, and 72 h after CPB. In both studies, patients were randomised into either the
      preconditioning group or the control group. Preconditioning was induced, after
      the onset of CPB, with two 3 min periods of crossclamping and an intervening 2
      min of reperfusion, followed by 10 min sustained ischaemia. The control group
      only received 10 min of sustained ischaemia. Ischaemic preconditioning resulted
      in a slower rate of ATP (mumol/g dry weight) depletion in the preconditioned
      hearts at the end of the 10 min of sustained ischaemia (preconditioned: 11.5 +/-
      0.8 vs control: 7.2 +/- 0.3; P < 0.005). Also, preconditioning resulted in a
      slower rate of troponin T release which was significantly different at 72 h after
      CPB in the preconditioned group (0.3 milligram) when compared with the control
      group (1.4 milligrams; P < 0.05). In addition, more patients in the
      preconditioned group had troponin T levels lower than 0.5 milligram at 72 h than
      in the control group (10 vs 3 patients). Both groups of patients received the
      same number of grafts, and underwent the same length of ischaemia during the
      procedure. We conclude that in patients undergoing CABG surgery, ischaemic
      preconditioning may reduce myocardial injury as shown by the favourable changes
      in myocardial ATP, and serum troponin T levels.

PMID- 9038497
TI  - Audit of thromboembolic prophylaxis in hip and knee surgery.
AB  - An audit of the departmental policy for thromboembolic prophylaxis was
      undertaken, examining the use of TED stockings, administration of subcutaneous
      low-dose heparin and inclusion into a multicentre pulmonary embolism prevention
      (PEP) trial for fractured neck of the femur. The results showed that despite an
      established unit policy, only 43% of patients undergoing primary hip replacement
      and 14% undergoing revision replacement received subcutaneous heparin. All
      patients undergoing primary and revision total knee replacement received
      subcutaneous heparin, but 75% of these patients received an incorrect dose. Use
      of TED stockings in patients who had sustained a fractured neck of the femur,
      ranged from 0% to 70% depending on the type of fixation. Use of subcutaneous
      heparin in these patients ranged between 0% and 20% and inclusion into the PEP
      trial from 0% to 20%. The results of this study were presented to the clinicians
      working in the orthopaedic department and 3 months later the audit cycle was
      completed by repeating the study. It was found there was a statistically
      significant improvement in the administration of subcutaneous heparin and in the
      wearing of TED stockings in the joint arthroplasty group as well as in the
      inclusion of hip fracture patients into the PEP trial. This study demonstrates
      that established protocols are of little value unless audited and that completion
      of the audit cycle is essential. It does not attempt to show that one
      prophylactic method is better than another.

PMID- 9038498
TI  - Pathological anatomy and dynamic effect of the displaced plantar plate and the
      importance of the integrity of the plantar plate-deep transverse metatarsal
      ligament tie-bar.
AB  - Normal and deformed forefeet have been investigated by cadaver anatomical
      dissections and experiments, by radiographs, CT and MRI scanning, and by clinical
      studies. Evidence is presented to show that the skeleton of the foot rests on and
      is controlled by a multi-segmental ligamentous and fascial tie-bar system.
      Transversely across the plantar aspect of the forefoot, the plantar plates and
      the deep transverse metatarsal ligaments form a strong ligamentous structure
      which prevents undue splaying of the forefoot. Longitudinally, the five digital
      processes of the deeper layer of the plantar fascia are inserted into the plantar
      plates and control the longitudinal arch of the foot. It is suggested that many
      forefoot deformities result from the failure of parts of the tie-bar system and
      the dynamic effect of displacement of the plantar plates. Understanding this
      allows a more logical approach to their treatment.

PMID- 9038499
TI  - Cardiac arrest from the use of diathermy during total hip arthroplasty in a
      patient with an external pacemaker.

PMID- 9038500
TI  - Improving attendance rates for abdominal aortic aneurysm screening.

PMID- 9038501
TI  - Improving postoperative care: the role of the surgeon in the high dependency
      unit.

PMID- 9038502
TI  - Research in the training of general surgeons: results of a survey.

PMID- 9038503
TI  - Foreign body impaction arising in adulthood: a result of neonatal repair of
      tracheo-oesophageal fistula and oesophageal atresia.

PMID- 9038504
TI  - Morbidity of varicose vein surgery: auditing the benefit of clinical practice.

PMID- 9038505
TI  - Morbidity of varicose vein surgery: auditing the benefit of changing clinical
      practice.

PMID- 9038506
TI  - Audit of pain after nasal surgery.

PMID- 9038507
TI  - Psychological outcomes amongst cleft patients and their families.
AB  - Our aims were to determine the psychological status of a sample of cleft lip and
      palate patients and their parents using standardised interviews and to assess
      subjects' satisfaction with cleft treatment. In all, 242 interviews of 112
      patients and 130 parents were carried out in nine base hospitals used for cleft
      treatment. 73% (n = 38) of 15- and 20-year-old subjects felt their self
      confidence had been very much affected as a result of their cleft. 60% of all 112
      interviewed patients were teased about speech or cleft related features. A
      significant minority of 15-year-old subjects (23%, n = 7) felt excluded from
      treatment planning decisions. Despite high levels of overall satisfaction with
      cleft care, 60% (n = 78) of parents and 37% (n = 41) of interviewed patients made
      suggestions for improvements. No agreement between parent/child pairs for their
      satisfaction with clinical outcome of cleft related features was found using the
      weighted kappa statistic to determine the level of agreement. Differences between
      parents' and their child's satisfaction ratings for cleft related features were
      not statistically significant except for the ratings for 'lip' (P < 0.005) and
      'teeth' (P < 0.05) for 15-year-old subjects (Wilcoxon signed rank sum test).
      Patients' views on planned treatment should therefore be independently sought
      from their parents' views, as no agreement was found within the groups for
      perceived satisfaction with clinical outcome. This study demonstrates the
      importance of identifying 'psychological outcome' as well as 'clinical outcome'
      in order to improve rehabilitation for cleft lip and palate patients. Seven
      families were referred for counselling for cleft-associated emotional problems as
      a result of this survey.

PMID- 9038508
TI  - Cutaneous malignant melanoma in the young.
AB  - Between the years 1967 and 1993, 3246 patients were diagnosed with malignant
      melanoma at Frenchay Hospital, Bristol. This paper reports 47 patients, 21 years
      of age or under, including 10 preadolescent cases under 14 years of age. It
      represents a further follow-up of a cohort originally published from this centre
      in 1986 in addition to 18 new cases. Most (89%) of the lesions occurred on the
      trunk and extremities, with females showing a predominance of lesions on the
      lower limbs. 83% of the melanomas were of the superficial spreading type: 72%
      invaded to Clark level III and IV. Thickness ranged from 0.29 mm to 50.00 mm
      (median 1.20 mm). Ulceration was present in 17% of cases and 32% of melanomas
      arose within a pre-existing small congenital melanocytic naevus. Overall 5-year
      survival was 81%, with a mean follow-up of 8.5 years. Ulceration and tumour
      thickness of greater than 1.5 mm were associated with a poor prognosis.

PMID- 9038509
TI  - The clinical significance of oncogene expression in subungual melanoma.
AB  - Subungual melanoma is a particularly aggressive tumour. However, biological
      investigations of its behaviour are presently lacking due to its comparative
      rarity. In order to study the biology of this disease, the activity of the c-myc
      oncogene was studied in tumours from 24 patients with subungual melanoma using
      the technique of flow cytometry. High levels of oncoprotein were found in all
      tumours and exceeded that documented in other varieties of cutaneous melanoma.
      Survival analysis revealed that stratification of patients according to oncogene
      activity provided a useful prognostic marker with shorter disease free interval
      (log rank test, chi 2 = 6.6, P = 0.01) and overall survival (log rank test, chi 2
      = 3.6, P = 0.07) in tumours with high oncoprotein levels. This is the first study
      to investigate oncogene expression in subungual disease and supports its
      potential application as a prognostic marker.

PMID- 9038510
TI  - Giant congenital naevus of the scalp and cranium: case report and review of the
      literature.
AB  - Congenital pigmented naevi are lesions that are usually confined to skin. We
      report a giant congenital naevus of the scalp which involved skin, galea, full
      thickness cranial bone, dura and the intracranial venous sinuses. The literature
      on giant congenital naevi with direct involvement of underlying bone is reviewed.

PMID- 9038511
TI  - An evaluation of the Wurzburg titanium miniplate osteosynthesis system for
      mandibular fixation.
AB  - We present an 8-year experience with the Wurzburg noncompression titanium
      miniplate system for the rigid fixation of the mandible during elective head and
      neck cancer surgery in a consecutive series of 100 patients. One half of the
      miniplates were used to fix mandibulotomies undertaken for surgical access. The
      remaining half were in patients undergoing reconstruction of segmental mandibular
      defects, the vast majority (92%) with vascularised bone grafts. One to four
      variously shaped miniplates were used per patient (mean = 1.5), plate size
      ranging from 4 to 40 holes. Fifteen patients (15%) developed complications which
      included 3 mandibular osteoradionecrosis, 8 broken, 5 infected, and 4 exposed
      plates. Three of the eight fractured plates were associated with nonunion. In
      this study, the main advantages of titanium miniplate fixation, namely case of
      application, decreased fixation time and malleability, were accompanied by a
      level of morbidity which, while comparing well with alternatives, may necessitate
      a reappraisal of this technique of fixation.

PMID- 9038512
TI  - Pneumosinus dilatans of the maxillary sinus: a report of two cases.
AB  - Two cases of the rare condition of pneumosinus dilatans of the maxillary sinus
      are presented. This is a rare differential diagnosis of a maxillary mass. The
      precise aetiology and pathogenesis is obscure. Because facial deformity may
      persist after construction of a naso-antral window alone, direct resection and
      reconstruction using bone grafts is recommended in addition to the creation of a
      naso-antral window, if required.

PMID- 9038513
TI  - Monitoring the free radial forearm flap in pharyngo-oesophageal reconstruction.
AB  - Monitoring the viability of the free radial forearm flap after pharyngo
      oesophageal reconstruction poses technical problems. A method of monitoring using
      a small island flap elevated distal to the main forearm flap is presented. This
      monitor flap is easy to elevate. It is placed externally and provides information
      about the perfusion of the buried reconstruction flap. Postoperative management
      requires only assessment of tissue colour, turgor, capillary refill and bleeding,
      as for standard skin flap monitoring.

PMID- 9038514
TI  - The 'turkey wattle' sign revisited: diagnosing parotid vascular malformations in
      the adult.
AB  - The turkey wattle sign describes enlargement of a facial mass on dependency of
      the head and when the sign is present it is pathognomonic of a vascular
      malformation or haemangioma. We present a case of vascular malformation of the
      parotid gland in which this sign was demonstrated. The clinical and radiological
      features of this rare parotid mass are discussed with reference to the
      literature.

PMID- 9038516
TI  - Endoscopic harvest of the tensor fasciae latae muscle flap.
AB  - Endoscopic harvest of the tensor fasciae latae muscle flap is presented. Two
      cases of abdominal wall hernia were treated with reinforcement of the abdominal
      wall using endoscopically harvested, pedicled tensor fasciae latae muscle flaps.
      The scars of the thigh after flap harvest were much shorter than the scar of the
      conventional open technique and the results were satisfactory. As the tensor
      fasciae latae muscle is easily undermined, we think it is appropriate to harvest
      the flap using an endoscope. Fascial grafts can also be harvested in the same
      manner as the pedicled flap.

PMID- 9038515
TI  - Endoscopic assisted otoplasty: a preliminary report.
AB  - The use of endoscopy in facial aesthetic surgery, especially the browlift, is
      becoming well accepted. We report on the use of an endoscopic assisted technique
      to correct prominent ears in 10 patients. The instruments were inserted through
      scalp incisions. No skin excision was performed. The posterior (medial) cartilage
      surface was weakened by abrasion with a custom-made abrader to create a new
      antihelical fold. Nonabsorbable sutures were inserted through one or two
      postauricular stab incisions to appose the scaphal cartilage and the mastoid
      fascia to hold the new fold. Surgical technique, results and advantages of the
      operation are discussed. A new classification of prominent ears was used in
      patient selection for the procedure.

PMID- 9038517
TI  - Excision of subcutaneous tissue for the treatment of axillary osmidrosis.
AB  - Axillary osmidrosis is a distressing problem. Medical treatment is often
      inadequate. Local excision of the apocrine and eccrine glands is the most
      effective method available but is often accompanied by significant morbidity. We
      report a modified surgical technique for the treatment of this condition. From
      January 1994 to December 1995, 46 patients (38 females, 8 males) with axillary
      osmidrosis have been treated by excision of the subcutaneous tissue via two
      transverse incisions, without removing skin. Sutures are used to anchor the skin
      to the axillary fascia. There is no need for a complicated tie-over dressing and
      postoperative arm restriction. All patients were followed up for a minimum of 6
      months (average 11.6 months). The patients were asked to complete a
      questionnaire. The results of malodour elimination were classified as good, fair
      and poor. Forty-one (89.1%) of the patients had good results, four (8.7%) had
      fair results, and one (2.2%) had a poor result. The average convalescent time was
      9.2 days. Twenty-six patients (57%) were very satisfied and recommended this
      procedure. Only one patient (2%) regretted having the operation. This operation
      has the advantages of a high success rate, low complication rate, and rapid
      recovery for the treatment of axillary osmidrosis.

PMID- 9038518
TI  - Open reduction and internal fixation of condylar fractures via an extended
      bicoronal approach with a masseteric myotomy.

PMID- 9038519
TI  - Beraprost sodium: a stable prostaglandin I2 analogue.

PMID- 9038520
TI  - Commentary: skill mix for radiologists and radiographers. Report on a meeting
      organized by the BIR Diagnostic Methods Committee, held at the Scientific
      Societies lecture Theatre, London, on 26 April 1996.

PMID- 9038521
TI  - Commentary: 1996 International Congress on Radiation Protection. Report on the
      Ninth International Congress of the International Radiation Protection
      Association, held in Vienna, 14-19 April 1996.

PMID- 9038522
TI  - Review article: endovascular treatments for intracranial aneurysms.
AB  - During the last 10 years, the development of flexible microcatheters which can
      navigate cerebral vessels to lesions deep within the brain, has allowed the
      treatment of an increasing range of intracranial pathologies, including
      aneurysms. Techniques to embolize aneurysms, either by occlusion of their parent
      artery or endosaccular packing with its preservation, have evolved largely in
      order to treat inoperable aneurysms. Endosaccular packing with thrombogenic coils
      has recently allowed embolization of smaller aneurysms to be performed in
      patients acutely ill after subarachnoid haemorrhage. The procedural morbidity
      associated with these endovascular treatments are less dependent on aneurysm site
      than conventional neurosurgical clipping and initial results are comparable.
      These developments are challenging current thinking on the surgical management of
      patients with intracranial aneurysms. This review describes the evolution and
      practice of current endovascular treatments and their possible implications for
      the future of neuroradiology.

PMID- 9038523
TI  - Fast CT for aortic dissection.
AB  - Results were evaluated in 81 patients with suspected acute aortic dissection who
      were examined on a fast CT system capable of a 1 s data acquisition time. 17
      patients had Type A and nine had Type B dissections. Radiological assessment
      provided 78 confident reports and expressed some uncertainty about the diagnosis
      in three patients. Overall sensitivity for aortic dissection was 96.2% and
      specificity was 96.4%. When 78 confident reports alone were considered, both
      sensitivity and specificity reached 100%. Reconstruction of data at 100 ms
      intervals allowed discrimination between artefacts in the ascending aorta and
      Type A dissections. CT can often be used as the single investigation prior to
      surgery for acute Type A dissections.

PMID- 9038524
TI  - Does bowel preparation improve the quality of intravenous urography?
AB  - Many radiology departments continue to use bowel preparation prior to intravenous
      urography (IVU) despite recent studies questioning its value. This prospective
      study was designed to test the hypothesis that bowel preparation does not affect
      the quality of IVU, the number of films taken, or the use of tomography. 144
      patients were randomized into three groups; 49 had no preparation, 48 received a
      mild stimulant laxative (Dulcolax), and 47 took an osmotic laxative (Citramag).
      The subsequent IVUs were then reviewed by two observers; the control and contrast
      films were scored for the presence of faecal residue, and the visibility of the
      renal tract, respectively. Patients were also questioned about the side effects
      of the two preparations. There was no significant difference in the scores for
      renal tract visibility in those patients receiving stimulant laxative when
      compared with the unprepared group. Those receiving the osmotic laxative had
      significantly less faecal residue but this was at the expense of an increased
      amount of bowel gas. The osmotic laxative group had significantly higher scores,
      indicating better visualization of the urinary tract, than the other groups, but
      no significant reduction in the number of radiographs taken or the use of
      tomography. This group also reported more side effects. Overall our results
      suggest that the routine use of a laxative prior to an IVU examination does not
      decrease the radiation dose and produces some patient inconvenience. The practice
      therefore cannot be routinely recommended.

PMID- 9038525
TI  - Hysterosalpingo-contrast sonography (HyCoSy) using Echovist-200 in the outpatient
      investigation of infertility patients.
AB  - This study describes the introduction of hysterosalpingo-contrast sonography
      (HyCoSy) as a first line outpatient investigation of uterine and tubal factors in
      two fertility units. 136 infertile women had transvaginal scanning before and
      during the intrauterine injection of contrast medium (Echovist-200). HyCoSy was
      successfully completed in 132 cases (97%) within a mean time of 12.6 +/- 8.4 (4
      50) min. The uterus and its cavity appeared normal in 108 (82%) women. Uterine
      abnormalities in the remaining 24 women (18%) included structural abnormality (n
      = 7), fibroids (n = 12) and endometrial polyps (n = 5). A total of 261 fallopian
      tubes in 132 women were assessed: 186 (71%) appeared patent and 55 (21%) blocked.
      The remaining 20 (8%) could not be assessed for technical reasons. Polycystic
      ovaries and ovarian cysts were diagnosed in eight women. The most common adverse
      effect was mild/moderate pain, similar to period pain, with 24 (18%) women
      requiring simple analgesia. HyCoSy is a simple and well tolerated outpatient
      procedure. The technique provides clinically valuable information about tubal
      patency, ovarian and uterine abnormalities.

PMID- 9038526
TI  - The significance of low grade right iliac fossa uptake on 99Tcm-HMPAO labelled
      white cell scans.
AB  - Technetium-99m HMPAO labelled white cell scanning is now an accepted method for
      assessing the activity of inflammatory bowel disease. However, false positive
      results have been demonstrated. This study was conducted to assess the
      significance of low grade uptake on 99Tcm-HMPAO labelled white cell scans in the
      right iliac fossa (RIF) in the context of possible inflammatory bowel disease
      (IBD). 32 patients over a period of 1 year had low grade RIF uptake as the
      predominant abnormality. 20 of these had no prior diagnosis of inflammatory bowel
      disease. Only one case in this group was subsequently diagnosed as having Crohn's
      disease. Nodular lymphoid hyperplasia (NLHP) and non-steroidal anti-inflammatory
      drugs (NSAIDs) were also associated with low grade RIF uptake. Possible
      explanations for these findings are discussed.

PMID- 9038527
TI  - Anaphylactic IgE and IgG1 production for hapten can be enhanced by contrast
      media.
AB  - Various side effects have been associated with the clinical use of contrast
      media. Immunological mechanisms have been proposed but there have been very few
      experimental studies with animal models. We have attempted to develop murine
      models to determine whether or not anaphylactic antibodies such as IgE and IgG1
      against hapten (DNP) were enhanced with contrast medium (iopamidol) as an
      adjuvant or if the contrast medium itself produced antibodies of the IgE class.
      The results showed that anti-hapten IgE and IgG1 production was greatly enhanced
      with immunogen plus contrast medium. Anti-contrast medium antibodies of the IgE
      class could not be detected by PCA reactions. The enhancement of IgE and IgG1
      production for hapten was associated with IL-4 release by the neutralization test
      used by monoclonal anti-IL-4 antibodies. This is the first observation to show
      that contrast media may have a strong adjuvant effect for the production of IgE
      and IgG1. This murine model demonstrates a possible immunological function of
      contrast media in vivo.

PMID- 9038529
TI  - Radiology in the neonatal intensive care unit: dose reduction and image quality.
AB  - This paper describes a prospective study of the diagnostic radiation doses
      received in a neonatal intensive care unit (NICU) for a representative
      radiological technique used at our institution for a number of years and a "low
      dose" technique similar to that recommended by the Commission of the European
      Communities (CEC). A 400 speed film-screen combination was used in both
      techniques. A total of 363 anteroposterior (AP) chest and abdominal films of 77
      neonates were accrued. For each radiograph, the entrance skin dose (FSD), energy
      imparted (EI) and mean whole body dose were determined. For a neonatal AP chest,
      there was an 18% reduction in the mean ESD per radiograph from 20.0 muGy for the
      representative technique to 16.4 muGy for the low dose technique (p < 0.0005).
      The reduction in the mean EI per radiograph values for the two techniques from
      7.9 muJ to 7.1 muJ (10%) was statistically significant at the p < 0.017 level,
      after compensating for the difference in mean field dimensions between the two
      patient cohorts. The mean whole body dose per radiograph reduction from 4.4 to
      3.5 muGy (20%) was statistically significant at the p < 0.0028 level. It was
      determined that the ESD and EI could be fitted by an exponential function in the
      equivalent patient diameter, a single parameter indicative of neonate size.
      Absolute excess childhood cancer mortality risk per film was estimated using risk
      factors derived for fetal exposures. A "worst case" absolute excess mortality
      risk per chest radiograph was estimated to be 1.40 x 10(-7) for the conventional
      technique and was further reduced to 1.11 x 10(-7) for the low dose technique. A
      blind comparison of patient-matched film pairs for each technique was performed
      by three radiologists using criteria similar to those specified by the CEC. No
      statistically significant difference in clinical image quality was found between
      the two techniques.

PMID- 9038528
TI  - Renal ultrasonic findings in sulphadiazine-induced renal failure.
AB  - The increased incidence of cerebral toxoplasmosis in AIDS has led to a resurgence
      in the use of sulphadiazine. One complication of this is acute renal failure
      secondary to sulphadiazine-induced crystalluria. Three cases are described which
      demonstrate a spectrum of ultrasound findings ranging from echogenic foci in the
      renal parenchyma to echogenic material in both dilated and non-dilated collecting
      systems. In patients with AIDS having sulphadiazine treatment, these ultrasonic
      findings suggest that sulphadiazine is the cause of the renal failure.

PMID- 9038530
TI  - Radiographic skills learning: procedure simulation using adaptive hypermedia.
AB  - The design and development of a simulation tool supporting learning of
      radiographic skills is reported. This tool has by textual, graphical and iconic
      resources, organized according to a building-block, adaptive hypermedia approach,
      which is described and supported by an image base of radiographs. It offers
      interactive user-controlled simulation of radiographic imaging procedures. The
      development is based on a commercially available environment (Toolbook 3.0,
      Asymetrix Corporation). The core of the system is an attributed precedence
      (priority) graph, which represents a task outline (concept and resources
      structure), which is dynamically adjusted to selected procedures. The user
      interface imitates a conventional radiography system, i.e. operating console,
      tube, table, patient and cassette. System parameters, such as patient
      positioning, focus-to-patient distance, magnification, field dimensions, tube
      voltage and mAs are under user control. Their effects on image quality are
      presented, by means of an image base acquired under controlled exposure
      conditions. Innovative use of hypermedia, computer based learning and simulation
      principles and technology in the development of this tool resulted in an enhanced
      interactive environment providing radiographic parameter control and
      visualization of parameter effects on image quality.

PMID- 9038531
TI  - Development of an experimental model for high dose rate endocavitary irradiation
      of the rat rectum.
AB  - Experimental data indicate a greater tolerance for endocavitary than for external
      beam irradiation of the normal rectal tissue in the rat. Increased tolerance has
      been attributed to temperature induced rectal hypoxia and a reduction of the dose
      to the mesentery. The general scarcity of experimental work in the field and the
      problems concerning hypoxia and dosimetry motivated the development of the
      current model. An 8 mm diameter endocavitary applicator was used for symmetrical
      dilatation and central introduction of the 192Ir source into the rectum of male
      Fischer F344 rats. Pulse oximetry and pO2-electrode readings from the intubated
      rectum gave no indication of radiobiological hypoxia. In vitro and in vivo
      thermoluminescence dosimetry (TLD) was supported by MRI based ferrous sulphate
      gel dosimetry. Using a 25 mm length source configuration the 90% isodose
      incorporated a 13 mm length segment of the rectum, and a 5.6% maximum deviation
      from the calculated dose was observed by the TLD and MRI based gel dosimetry. The
      ureters, the bladder and the skin were the only organs other than the target
      organ which received doses greater than 10% of the rectal dose. The model seems
      to be suitable for dose effect studies since endocavitary irradiation of the rat
      rectum can be performed without induction of local tissue hypoxia.

PMID- 9038532
TI  - Bladder dose estimation during intracavitary brachytherapy for carcinoma of the
      cervix using a single line source system.
AB  - The estimation of maximum bladder doses from orthogonal radiographs is unreliable
      when triple source systems are used for intracavitary brachytherapy (BT) for
      gynaecological cancers. For single line source systems, the estimation of maximum
      bladder doses from radiographs should be more reliable due to the radial symmetry
      of the isodose distribution. A pilot study has been carried out to compare the
      estimated maximum bladder doses from standard radiographs with data obtained from
      CT for single line source BT treatments. 12 patients undergoing treatment for
      carcinoma of the cervix were selected for CT assessment of their bladder doses.
      For each patient, the dose rates at the International Commission of Radiation
      Units and Measurements (ICRU) bladder reference point B1 and a second reference
      point B2 2.5 cm cranially were computed from orthogonal radiographs and were
      compared with the maximum bladder dose rate as determined by CT scanning. Dose
      rates were computed for two different source loading patterns: (1) a 6 cm line
      source with uniformly distributed linear activity along its length; (2) a 6 cm
      line source with increased activity in the central 2 cm segment. The mean ratio
      of the maximum CT bladder dose rate to the dose rate at the ICRU reference point
      B1 on orthogonal radiographs for the line source with uniform linear activity was
      1.32 (range 0.62-2.43, SD = 0.54). When the dose rates at both reference points
      B1 and B2 were considered, the mean ratio of the maximum CT dose rate to the
      maximum dose rate from radiographs was only 1.05 (range 0.72-1.72, SD = 0.24).
      For the line source with increased activity in the central segment, the mean
      ratio of the maximum CT bladder dose rate to the dose rate at B1 was 1.38 (range
      0.60-2.63, SD = 0.64). When both B1 and B2 were considered, the variation in the
      ratio of the maximum CT dose rate to the maximum dose rate from radiographs was
      considerably smaller (mean ratio = 1.07, range 0.69-1.76, SD = 0.26). For single
      line source systems, single point dose estimation using the ICRU reference point
      on orthogonal radiographs will underestimate the maximum bladder dose although
      the discrepancy is less than for triple source systems. If the ICRU reference
      point is used in conjunction with a second reference point 2.5 cm cranially, then
      underestimation of the maximum bladder dose is unlikely to occur as at least one
      of the points is likely to be a reasonable estimate of the maximum bladder dose.

PMID- 9038533
TI  - Case report: intravascular lipoma of the superior vena cava--CT and MRI
      appearances.
AB  - Intravascular lipomata are rare tumours occurring in the major central veins. We
      report a case in which an asymptomatic lipoma of the superior vena cava presented
      as mediastinal widening on a chest radiograph. The CT and MR features are
      presented.

PMID- 9038535
TI  - Pictorial review: foot axes and angles.
AB  - Using radiographs and diagrams, this article reviews the most commonly used axes
      and angles of the foot, including: longitudinal axis of the rearfoot, collum tali
      axis, talocalcaneal angle, cuboid abduction angle, longitudinal axis of the
      lesser tarsus, lesser tarsus angle, talonavicular angle, longitudinal axis of the
      metatarsus, forefoot adductus angle, metatarsus adductus angle, first
      intermetatarsal angle, hallux valgus angle, proximal and distal articular set
      angles, and hallux interphalangeal angle, plane of support, collum tali axis,
      talar declination angle, calcaneal inclination axis, lateral talocalcaneal angle,
      first metatarsal declination axis and calcaneal inclination angle.

PMID- 9038534
TI  - Case report: sclerotic skeletal haemangiomatosis presenting with spinal cord
      compression--CT and MRI findings.
AB  - We report the case of a 59-year-old man with skeletal haemangiomatosis who
      presented with progressive bilateral lower extremity weakness. Computed
      tomography (CT) and magnetic resonance imaging (MRI) located the causative lesion
      in the neural arch of the T4 vertebra. CT demonstrated osseous expansion with a
      mixed lytic and sclerotic pattern. MRI of the lesion showed hypointensity on T1
      weighted images, mixed signal intensity on T2 weighted images and moderate
      contrast enhancement. Similar but less extensive lesions were present in other
      vertebrae as well as ribs.

PMID- 9038536
TI  - Case of the month: a lytic lesion in bone.

PMID- 9038537
TI  - Dose rates and energy spectra in the maze of a linear accelerator treatment room.

PMID- 9038538
TI  - Somatostatin in pancreatic disease.

PMID- 9038539
TI  - Gut barrier function in the surgical patient.

PMID- 9038540
TI  - Papillary microcarcinoma of the thyroid gland.
AB  - Papillary microcarcinomas are a specific subgroup of papillary thyroid cancer.
      They have the same histological features as papillary thyroid cancer but are 1.0
      cm or less in diameter. These tumours are a common incidental finding at autopsy
      and in thyroid glands excised for other pathology. This tumour can metastasize to
      regional lymph nodes but its ability to cause significant morbidity and mortality
      has been questioned. As papillary microcarcinomas can represent up to 30 per cent
      of all papillary cancers seen in a thyroid surgeon's practice, they are an
      important group. The aim of this review article is to outline the natural history
      of papillary microcarcinoma and to offer therapeutic management strategies.

PMID- 9038541
TI  - Oesophageal function testing and antireflux surgery.
AB  - Despite the increasing emphasis that is placed on both pH measurement and
      oesophageal manometry, there is little consensus about their usefulness in the
      clinical setting. These tests are far from infallible and it is difficult to
      support their universal application in patients with gastrooesophageal reflux
      disease. Nevertheless, these imperfect tests are useful in certain situations and
      clinicians must strive to use them intelligently for those most likely to
      benefit.

PMID- 9038542
TI  - Laparoscopic fenestration in polycystic liver disease.
AB  - Sixteen laparoscopic cyst fenestrations for symptomatic adult polycystic liver
      disease (APLD) were performed in 13 women, including four patients who had had
      previous attempts at treatment (percutaneous sclerotherapy in two and
      fenestration via a laparotomy in two). The median number of cysts deroofed was 32
      (range 18-58) during the 13 primary procedures. There was no in-hospital death.
      Postoperative transient ascites occurred in six patients. After operation 11
      patients experienced immediate relief of symptoms but during a median follow-up
      of 26 (range 6-49) months, eight of these patients developed recurrent symptoms.
      Two patients underwent three repeat laparoscopic fenestrations, at which time
      perihepatic adhesions were rare and no complication occurred. Because repeat
      procedures may be performed, laparoscopic fenestration appears to be useful for
      the treatment of symptomatic APLD. However, it is less effective than
      fenestration at open surgery or liver resection and should be employed only in
      patients with predominantly large cysts.

PMID- 9038543
TI  - Effect of previous sclerotherapy on the outcome of gastro-oesophageal
      devascularization and oesophageal transection in bleeding oesophageal varices.
AB  - This retrospective analysis studied the effect of sclerotherapy on subsequent
      oesophageal transection in the management of patients with bleeding oesophageal
      varices and compared the result with that in those who did not receive
      sclerotherapy as the primary treatment. Fifty patients were treated by gastro
      oesophageal devascularization and oesophageal transection for bleeding
      oesophageal varices over a 4-year period. Twenty-six patients did not receive
      sclerotherapy (group 1) and 24 received between one and four sessions of
      sclerotherapy (group 2) before surgery. Oedema and thickness of the lower end of
      the oesophagus and some adhesions were noted during surgery in patients who had
      had previous sclerotherapy; however, stapled oesophageal transection and
      anastomosis could be performed in all these patients. There was no oesophageal
      leak in any patient, although there was a higher rate of chest complications
      (nine versus six patients) in group 2. Six patients (12 per cent) died (three in
      each group) during the postoperative period; three had Child grade C disease. It
      is concluded that the decision to operate to control bleeding varices should be
      made early. One or two sessions of sclerotherapy before surgery does not increase
      intraoperative difficulty or the postoperative leak rate following oesophageal
      transection. The outcome of surgery is directly related to the state of liver
      reserve (Child grade).

PMID- 9038544
TI  - Influence of cholecystectomy on bile duct width.

PMID- 9038545
TI  - Pneumonia presenting with acute abdominal pain in children.

PMID- 9038547
TI  - Quick and simple distal pancreatectomy using the GIA stapler: report of 35 cases.

PMID- 9038546
TI  - Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the
      gallbladder.
AB  - The majority of patients with advanced carcinoma of the gallbladder have
      irresectable disease and require palliation for jaundice, pruritus and
      cholangitis. Intrahepatic segment III cholangiojejunostomy has been described for
      palliation of high biliary obstruction in these patients. Forty-one patients with
      stage IV gallbladder cancer underwent intrahepatic segment III
      cholangiojejunostomy. Subsequent jaundice, pruritus and cholangitis were
      documented; liver function tests and isotope hepatobiliary scans were performed.
      All patients had jaundice, 29 had pruritus and 12 had cholangitis. Postoperative
      complications included anastomotic leak in six patients and wound infection in
      six. Five patients died within 30 days of operation. Thirty-two patients were
      available for follow-up. The procedure failed to relieve jaundice, pruritus or
      cholangitis in four patients; 18 were free of jaundice, pruritus and cholangitis
      until death or last follow-up, and ten had recurrent jaundice or cholangitis.
      Isotope scanning was found to be useful to predict success of the procedure.
      Intrahepatic segment III cholangiojejunostomy provided excellent palliation from
      jaundice, pruritus and cholangitis with acceptable mortality and morbidity rates
      in patients with advanced carcinoma of the gallbladder.

PMID- 9038548
TI  - Outcome of treatment for distal bile duct cancer.
AB  - All patients with distal bile duct tumours over a 10-year period (October 1983 to
      December 1993) were identified by means of a prospective database. The medical
      records of 104 patients were reviewed. Univariate and multivariate analysis for
      predictors of outcome was performed. Median age of the patients was 65 (range 30
      89) years. Patients presented with a clinical picture indistinguishable from that
      of pancreatic ductal adenocarcinoma. Twenty patients had no surgical treatment
      and 23 had a diagnostic laparotomy only. Biliary bypass was performed in 16
      patients and radical resection was performed in 45 (pancreaticoduodenectomy, 39;
      bile duct excision, six). Operative mortality occurred in two of 45 patients
      having radical resection and complications in 17. Resection provided significant
      survival benefit. By univariate and multivariate analysis, resectability and
      negative node status (P < 0.001) were the only predictors of favourable outcome.
      Sex, age, preoperative stenting, grade of tumour and bilirubin level did not
      predict outcome. The 5-year survival rate for radically resected, node-negative
      tumours was 54 per cent. Surgical resection is effective therapy for distal bile
      duct tumours. These patients have a better outlook than those having resection of
      pancreatic adenocarcinoma.

PMID- 9038549
TI  - Biliary papillomatosis.

PMID- 9038550
TI  - Complete prevention of impaired anastomotic healing in diabetic rats requires
      preoperative blood glucose control.
AB  - Uncontrolled diabetes severely impairs early healing of experimental intestinal
      anastomosis. This study aimed to compare the potential beneficial effect of
      insulin treatment, started before or immediately after surgery. A normal blood
      glucose level was attained in diabetic rats by twice-daily administration of
      insulin, commenced either 4 days before operation (insulin-1 group) or on the day
      of operation (insulin-2 group). A non-diabetic control group and an uncontrolled
      diabetic group were also studied. Three days after operation, mean(s.d.) bursting
      pressures in the diabetic group were severely reduced compared with those in
      controls: 1.0(1.4) versus 8.1(2.9) kPa in the ileum and 4.9(4.7) versus 18.1(5.8)
      kPa in the colon. For ileal anastomosis, values in both groups of animals
      receiving insulin were similar to those in controls, but for colonic anastomosis
      the mean bursting pressure in the insulin-2 group remained significantly (P <
      0.017) below that in the insulin-1 group (10.2(6.4) versus 20.7(7.9) kPa
      respectively). After 7 days mean bursting pressures in both ileum and colon were
      restored to control levels in the insulin-1 group but not in the insulin-2 group.
      Anastomotic abscess formation after 3 days was also significantly (P < 0.017)
      more common in the diabetic and insulin-2 groups, but not in the insulin-1 group
      than in the control group. Postoperative blood glucose control alone does not
      completely prevent the detrimental effects of uncontrolled diabetes on healing
      intestinal anastomoses.

PMID- 9038551
TI  - Pitfalls in the management of preauricular sinuses.
AB  - A total of 159 operations for the excision of a preauricular sinus carried out in
      117 patients over an 8-year period were reviewed. Previous excision, the use of a
      probe to delineate the sinus and operating under local anaesthesia all increased
      the chance of recurrence. The condition recurred more often in patients who
      developed post-operative wound sepsis than in those who healed primarily. Means
      of decreasing the recurrence rate include: (1) meticulous dissection of the sinus
      by an experienced head and neck surgeon under general anaesthesia; (2) the use of
      an extended preauricular incision; (3) clearance down to the temporalis fascia to
      ensure complete removal of all epithelial components; (4) avoidance of sinus
      rupture; and (5) closure of wound dead space.

PMID- 9038552
TI  - Colour-coded duplex imaging can safely replace diagnostic arteriography in
      patients with lower-limb arterial disease.
AB  - The purpose of this study was to review the outcome of adopting colour-coded
      duplex ultrasonography as the primary imaging modality in patients with
      symptomatic lower-limb arterial disease. Over a 12-month period 467 consecutive
      lower-limb duplex scans were performed of which 437 (94 per cent) were
      technically adequate. Of the 467 limbs, 184 (39 per cent) were managed
      conservatively, 230 (49 per cent) were referred for percutaneous transluminal
      angioplasty (PTA), 41 (9 per cent) underwent reconstructive surgery and 12 (3 per
      cent) required diagnostic arteriography. In patients referred for PTA there were
      only 22 (10 per cent) unexpected findings; there was agreement about superficial
      femoral artery occlusion length in 95 (89 per cent) of 107 limbs and about the
      presence or absence of a superficial femoral artery stump in 91 (85 per cent) of
      107 cases. In patients referred for surgery there were no unexpected findings.
      Colour-coded duplex imaging can safely replace diagnostic arteriography in up to
      97 per cent of lower limbs with arterial disease.

PMID- 9038553
TI  - Diagnosis and therapy of aortic prosthetic fistulas: trends over a 30-year
      experience.
AB  - A retrospective study was carried out of patients from a single institution over
      a 30-year period. Thirty-one patients presented with 33 fistulas, four non
      enteric and 27 enteric. In 25 of 27 patients with a prosthesis-related enteric
      fistula gastrointestinal bleeding was present. Angiography revealed the fistula
      in five patients endoscopy in three, and barium studies, echography and computed
      tomography each revealed one fistula. Six patients died before and five died
      during operation. In 20 patients various techniques were used for treatment. In
      hospital mortality decreased from six of eight patients before 1970, to seven of
      ten between 1971 and 1980, and to four of 13 after 1981. In the long term,
      patients treated with an extra-anatomic reconstruction had a poorer prognosis
      than those treated by in situ reconstruction. This experience shows that
      diagnostic tests often fail to reveal a prosthesis-related fistula and that
      mortality can be substantially reduced by early exploration in patients with
      negative diagnostic studies.

PMID- 9038555
TI  - Transposition of the anorectum to the abdominal wall.

PMID- 9038554
TI  - Prospective randomized study of a new method of providing postoperative pain
      relief following femoropopliteal bypass.
AB  - The extensive incision required for femoropopliteal bypass using saphenous vein
      causes significant postoperative pain, principally within the distribution of the
      cutaneous branches of the femoral nerve. This prospective randomized study
      investigated the efficacy of continuous postoperative femoral nerve block in
      reducing both pain (visual analogue pain score) and the requirement for opiate
      analgesia. Ten patients received a femoral nerve block by infusion of 0.5 per
      cent bupivacaine (5 ml/h for 48 h) via an epidural catheter together with a
      patient-controlled analgesia (PCA) device containing morphine; a further ten
      patients used a PCA device alone. The median postoperative intravenous morphine
      requirement was significantly reduced in patients with a nerve block at 24 h (4
      versus 33 mg, P < 0.01) and at 48 h (5 versus 37 mg, P < 0.01) compared with
      controls. Postoperative pain was effectively abolished in the former group. The
      addition of a nerve block to PCA provides superior pain control after
      femoropopliteal bypass.

PMID- 9038556
TI  - Prognostic value of negative intraoperative ultrasonography in primary colorectal
      cancer.
AB  - The risk of developing recurrent tumour was assessed in a group of 85 patients
      with primary colorectal cancer who had a negative intraoperative ultrasonographic
      examination at the time of primary tumour resection. At a median follow-up of 40
      months liver metastases had developed in 14 patients (16 per cent). Dukes
      classification of the primary tumours was stage A, B and C in one, three and ten
      patients respectively. The interval between primary tumour resection and
      detection of metastases varied from 6 to 24 months but all became evident within
      2 years. Sixteen patients (19 per cent) presented with extrahepatic recurrence,
      one of whom also developed liver metastases. A negative intraoperative
      ultrasonographic examination did not prove to be a favourable prognostic factor
      which allowed exclusion from follow-up or adjuvant chemotherapy.

PMID- 9038557
TI  - Ambulatory manometric examination in patients with a colonic J pouch and in
      normal controls.
AB  - Anorectal function after anterior resection may be impaired as a result of
      reduced luminal capacity in the pelvis. The aim of this study was to evaluate the
      colonic J pouch neorectum by means of ambulatory manometry. Twelve patients with
      a colonic pouch following anterior resection and seven healthy controls were
      studied for a median of 6 (range 6-24) h using a probe with two pouch-rectal and
      two anal canal transducers. Records were interpreted by visual inspection.
      Pressure values and wave frequencies were determined by software analysis.
      Pouches had been functioning for a median of 32 (range 11-55) months. All
      patients with a pouch had an acceptable stool frequency. Seven of 12 patients
      complained of incomplete evacuation. Resting anal canal pressure (73 versus 100
      cmH2O), pouch-rectal pressure (29 versus 15 cmH2O) and anal canal pouch-rectal
      pressure gradients (60 versus 85 cmH2O) were similar in patients and controls.
      The frequency of slow-wave activity in patients with a pouch was significantly
      lower than that in controls (7 versus 16 cycles per min, P = 0.001). Coordination
      between the colonic J pouch and the anal canal, in the form of sampling episodes,
      was observed in more than half of the patients with a functioning pouch. Large
      isolated contractions (pressure greater than 30 cmH2O and lasting longer than 20
      s) and rhythmic contractions were the most frequent pattern of pouch motility.

PMID- 9038558
TI  - Clinical significance of the tumour capsule in the treatment of parotid
      pleomorphic adenomas.
AB  - The propensity of pleomorphic adenomas to recur is generally attributed to the
      biological nature of the tumour, and surgery close to the capsule is perceived as
      undesirable. At the Christie Hospital, Manchester, between 1947 and 1992, 475
      tumours arising within the superficial portion of the parotid gland were treated
      by two surgical techniques: extracapsular dissection (380 patients) and
      superficial parotidectomy (95). Recurrence rates were 2 per cent in each group
      (median follow-up 12.5 years). Contact of the tumour with the facial nerve was
      recorded in 51 per cent of patients. There was no difference between the
      treatment groups in the incidence of permanent facial nerve injury (2 versus 1
      per cent respectively). This study demonstrates that dissection in close
      proximity to the tumour is possible without inducing recurrence and that in
      practice the microinvasion of the capsule by tumour buds has limited clinical
      significance.

PMID- 9038559
TI  - Long-term follow-up of over 1000 patients with salivary gland tumours treated in
      a single centre.
AB  - Between 1947 and 1992, 1403 patients with 1432 salivary gland tumours were
      treated at the Christie Hospital, Manchester. There were 1194 epithelial
      neoplasms: parotid, 1082 (91 per cent); submandibular, 47 (4 per cent); minor
      glands, 65 (5 per cent). The commonest histological diagnoses were pleomorphic
      adenoma (n = 776) and adenolymphoma (n = 159). A total of 244 carcinomas were
      seen (adenoid cystic carcinoma, n = 75). Treatment was primarily surgical,
      conservative where possible, and determined by tumour extent and not histology.
      Adjuvant radiation therapy was used in over half the definitively treated
      malignancies. The recurrence rate following the treatment of 551 new parotid
      pleomorphic adenomas was 1.6 per cent at median follow-up 12.5 (range 1-34)
      years, increasing to 15 per cent in the secondarily referred group (n = 170). For
      patients with definitively treated primary salivary carcinomas (n = 148), the
      disease-free survival rate at 5, 10 and 15 years was 58, 47 and 45 per cent
      respectively. Using multivariate analysis, clinical stage was the most important
      predictor of survival; the 10-year survival rate for stages I-IV was 96, 70, 47
      and 19 per cent respectively.

PMID- 9038561
TI  - Thoracoscopic parathyroidectomy of an ectopic mediastinal adenoma.

PMID- 9038560
TI  - Cyclosporin A and multiple fibroadenomas of the breast.
AB  - Multiple bilateral fibroadenomas are uncommon. This finding in four women who had
      received renal transplants prompted further inquiry. A prospective study was
      performed on 39 women under the age of 55 years who had received a renal
      transplant at least 1 year earlier. Clinical examination and breast
      ultrasonography were performed. Factors considered included immunosuppressive
      therapy, concurrent medication and renal function. Blood was taken for estimation
      of oestradiol, prolactin, follicle-stimulating hormone (FSH) and sex hormone
      binding globulin levels. Fibroadenomas were found in 13 of 29 women who had
      received cyclosporin A: multiple in ten and bilateral in five. No abnormal breast
      findings were seen in 10 patients immunosuppressed with steroids and azathioprine
      alone (chi 2 = 7.30, 1 d.f., P < 0.01). Serum oestradiol concentration was raised
      in women with fibroadenomas compared with that in those with normal breasts (P <
      0.05) and the level of FSH was lower (P < 0.01). Cyclosporin A may act on breast
      fibroblasts by humoral mechanisms and direct action.

PMID- 9038562
TI  - A 45-year perspective of congenital diaphragmatic hernia.
AB  - The records of 174 consecutive patients with congenital diaphragmatic hernia were
      reviewed to analyse the changes in the presentation, treatment and outcome during
      the 45-year interval from 1948 to 1992. For comparison the period was divided
      into years 1948-1962, 1963-1972, 1973-1982 and years 1983-1992. The proportion of
      high-risk cases (symptomatic within 6 h of birth) increased from 50 per cent
      during the first period to 77 per cent during the second, to 86 per cent during
      the third and to 94 per cent during the fourth. The primary mortality rate (death
      within 30 days of diaphragmatic repair) increased from 25 per cent during the
      first period to 35 per cent during the second, 46 per cent during the third and
      49 per cent during the fourth. No change occurred in the proportion of infants
      with diaphragmatic hernia who were stillborn or who died in the maternity unit.
      Post-mortem lung weight was available in 56 children. Severe pulmonary hypoplasia
      correlated with early postoperative death and clinical severity. The mean(s.d.)
      lung weight ratio (combined lung weight divided by the lung weight expected for
      the body-weight) decreased from 0.70(0.49) during the second period to 0.56(0.36)
      during the third and 0.40(0.18) during the fourth. The increased proportion of
      more severe cases with very hypoplastic lungs explains the rise in the mortality
      rate of patients operated on for congenital diaphragmatic hernia. This may
      reflect a real change in the disease spectrum rather than improved referral.

PMID- 9038563
TI  - Prospective randomized study of sulindac versus calcium and calciferol for upper
      gastrointestinal polyps in familial adenomatous polyposis.
AB  - Eighteen patients with familial adenomatous polyposis (FAP) who had previously
      undergone colectomy but had upper gastrointestinal polyps were studied in a
      double-blind randomized crossover trial comparing sulindac with calcium and
      calciferol. Sulindac produced a reduction in the crypt proliferation index in the
      gastric epithelium of patients but did not significantly affect duodenal mucosa.
      Calcium with calciferol did not have any effects on crypt proliferation index in
      patients with FAP.

PMID- 9038564
TI  - Parallel self-expanding covered metal stents in the trachea and oesophagus for
      the palliation of complex high tracheo-oesophageal fistula.

PMID- 9038565
TI  - Palliation of oesophageal carcinoma using the argon beam coagulator.
AB  - Oesophageal intubation occasionally fails to palliate inoperable carcinoma: some
      tumours are unsuitable for this procedure and others overgrow the tube. This
      study reports a series of nine patients (median age 79 (range 55-87) years) in
      whom the argon beam monopolar coagulator via a flexible endoscopic probe was used
      to ablate such tumours. Fourteen ablation procedures were performed. The
      endoscope was passed to the stomach at the end of each procedure. There were no
      complications; the median hospital stay was 2 (range 1-13) days. Thirteen
      procedures rendered the patients completely asymptomatic for a median of 6 (range
      4-12) weeks. Six patients died a median of 14 (range 4-38) weeks after the first
      ablation, reflecting their limited life expectancy. The argon beam coagulator
      provides an effective alternative to laser ablation, being considerably cheaper
      and safer, while maintaining the minimally invasive nature of the palliation.

PMID- 9038566
TI  - Quality of life following resection of oesophageal carcinoma.
AB  - Quality of life following resection of oesophageal carcinoma was assessed by
      patients using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire and by a psychologist using the Spitzer Index.
      Quality of life was evaluated in 119 patients on one occasion 12 months after
      operation and in 30 patients regularly, starting with a preoperative assessment.
      Self and external evaluation showed a significant correlation (r = 0.61), but
      quality of life was assessed as being higher by the external observer. Limited
      physical performance status and somatic complaints were the most important
      postoperative dysfunctions, whereas emotional, social and economic disorders were
      found to be less frequent and less severe. Of several factors analysed only
      tumour recurrence (P < 0.01) and anastomotic stricture (P < 0.05) lowered quality
      of life significantly. Compared with the preoperative assessment, quality of life
      had decreased on discharge from hospital but was restored within 6 months of
      operation in disease-free patients. Further studies are required to determine the
      impact of adjuvant therapy for quality of life in patients undergoing surgery for
      oesophageal cancer.

PMID- 9038567
TI  - Impact of splenectomy on circulating immunoglobulin levels and the development of
      postoperative infection following total gastrectomy for gastric cancer.
AB  - Splenectomy increases the postoperative morbidity of total gastrectomy for
      carcinoma of the stomach. The reasons for this increased risk of postoperative
      infection are unknown. The aim of this study was to evaluate the impact of
      splenectomy on circulating immunoglobulin levels and to determine whether
      splenectomy was an independent risk factor for the development of postoperative
      infection in 154 patients undergoing total gastrectomy for carcinoma of the
      stomach. Splenectomy reduced circulating immunoglobulin M levels in the early
      postoperative period following total gastrectomy. However, it was not identified
      as an independent risk factor for the development of postoperative infection by
      multivariate analysis.

PMID- 9038568
TI  - High prevalence of Helicobacter pylori infection in duodenal ulcer perforations
      not caused by non-steroidal anti-inflammatory drugs.
AB  - There has been controversy regarding the relationship between Helicobacter pylori
      and perforated peptic ulcer, which is known to have a high recurrence rate if
      only simple patch repair is performed. The aim of this study was to evaluate the
      association between H. pylori infection and intake of non-steroidal anti
      inflammatory drugs (NSAIDs) in patients with perforated duodenal ulcers. Of the
      73 patients recruited over a 16-month period, 51 (70 per cent) had evidence of H.
      pylori infection by intraoperative gastroscopy and antral biopsies. The infection
      rate rose to 80 per cent if NSAID users were excluded. The H. pylori-infected
      group was significantly younger (mean 47.6 versus 62.5 years), with a male
      preponderance (49 of 51 versus 14 of 22 patients), and had significantly less
      NSAID consumption (three of 51 versus ten of 22) and more prolonged dyspepsia (40
      of 51 versus ten of 22), compared with H. pylori-negative patients. H. pylori
      infection probably plays an important role in the causation of non-NSAID-induced
      duodenal ulcer perforation. Whether eradication of the bacteria can alleviate the
      strong ulcer diathesis in this subgroup of patients is unknown.

PMID- 9038569
TI  - Abnormal suntanning following transthoracic endoscopic sympathectomy.

PMID- 9038570
TI  - Surgical care in octogenarians.
AB  - The general surgical profile of octogenarians compared with that of younger
      patients, and risk factors predictive of operative mortality and morbidity, were
      determined retrospectively using a computer database for all patients admitted
      between 1989 and 1993. There were 934 admissions of octogenarians and surgery was
      performed in 447 cases (47.9 percent). The admission rate of patients over 80
      years of age increased during the 5-year period from 4.6 to 9.0 per cent, and was
      significantly higher than that of geriatric patients aged 65-79 years (P < 0.01).
      Emergency admissions (63.6 percent) and operations (42.3 percent) were more
      frequent in patients aged over 80 years (P < 0.01); emergency operations
      increased during the 5 years from 38 to 59 percent. Altogether, 83 deaths and 171
      complications were recorded. The mortality rate of octogenarians was greater than
      that of younger patients (P < 0.01). Postoperative mortality and morbidity rates
      were 10.1 and 32.2 percent respectively. After multiple logistic regression
      analysis with stepwise backward elimination, an American Society of
      Anesthesiologists score of II-V (P < 0.01), the presence of two associated
      diseases (P < 0.01) and laparotomy procedures (P < 0.03) appeared to be
      independent risk factors for postoperative mortality and morbidity.

PMID- 9038571
TI  - Preoperative risk assessment in elective general surgery.
AB  - Despite improved surgical techniques there is still a risk of mortality in
      elective general surgery. In a prospective study preoperative data from 3250
      patients were collected and compared with postoperative systemic complications,
      using univariate chi 2 analysis. Highly significant (P < 0.00001) variables were
      subjected to stepwise logistic regression analysis. The severity of operative
      procedure, higher American Society of Anesthesiologists (ASA) grade, symptoms of
      respiratory disease and malignancy were found to be significant risk factors
      predicting postoperative morbidity (P < 0.05). Using these four variables, a
      simple preoperative risk scoring system has been defined. Class A (up to 5
      points) was defined as a low-risk group (systemic complication rate 5.0 per
      cent), class B (5-7 points) was intermediate risk (systemic complication rate
      17.9 per cent) and class C (8-10 points) was high risk (systemic complication
      rate 33.3 per cent). Patients at high risk for perioperative and postoperative
      complications are more likely to be identified by this analysis than by using the
      ASA classification alone.

PMID- 9038572
TI  - Chemical composition and potential hazards of electrocautery smoke.

PMID- 9038573
TI  - Port-site metastases following diagnostic laparoscopy.

PMID- 9038574
TI  - Laparoscopic inguinal hernia repair.

PMID- 9038575
TI  - Sengstaken tube for bleeding rectal angiodysplasia.

PMID- 9038576
TI  - Preliminary experience with butyl-2-cyanoacrylate adhesive in tension-free
      inguinal hernia repair.

PMID- 9038577
TI  - Pulmonary function after laparoscopic cholecystectomy in the elderly.

PMID- 9038578
TI  - Prospective study of the aetiology of infusion phlebitis and line failure during
      peripheral parenteral nutrition.

PMID- 9038579
TI  - Stapling instruments for intestinal anastomosis in colorectal surgery.

PMID- 9038580
TI  - A better bridge for loop stomas.

PMID- 9038581
TI  - Simultaneous aortorenal homograft transplantation: expanding the indications for
      renal and vascular replacement.

PMID- 9038582
TI  - Diagnostic role of cytology in screen-detected breast cancer.

PMID- 9038583
TI  - Prognostic significance of radial margins of clearance in rectal cancer.

PMID- 9038584
TI  - Conservative management of fibroadenoma of the breast.

PMID- 9038585
TI  - Use of laparoscopic trocar for percutaneous introduction of drains into intra
      abdominal abscess.

PMID- 9038586
TI  - Regulation of adipose cell number in man.
AB  - 1. Adipose tissue mass is dependent on both the average volume and the number of
      its constituent adipocytes. Significant alteration in body mass involves
      alteration in both adipocyte volume and number. 2. Increases in adipocyte number
      occur via replication and differentiation of preadipocytes, a process which
      occurs throughout life. Decreases in adipocyte number occur via preadipocyte and
      adipocyte apoptosis, and possibly adipocyte dedifferentiation. 3. Overall
      regulation of adipose mass involves endocrine, paracrine and possibly autocrine
      systems. Hypothalamic centres appear to control appetite, metabolic rate and
      activity levels in a co-ordinated manner. Within the hypothalamus, known weight
      regulatory molecules include glucagon-like peptide-1, neuropeptide Y and leptin.
      Leptin is a major afferent signal from adipose tissue to the hypothalamus,
      providing information on overall adipose tissue mass. However, the precise means
      by which the hypothalamus signals to adipose tissue is less well understood. 4.
      In adipose tissue, known molecular regulators of adipose cell number include
      insulin, ligands for the peroxisome proliferator activated receptor-gamma,
      retinoids, corticosteroids and tumour necrosis factor-alpha. The net effect of
      these and other regulators is to effect a concerted alteration in adipocyte
      volume and number. This review largely focuses on the control of fat cell
      acquisition and loss and the influence of these processes on adipose tissue mass
      and regional distribution.

PMID- 9038587
TI  - Cardiovascular pharmacology of purines.
AB  - 1. This review focuses on the extracellular actions of ATP and adenosine, and in
      particular their role in cardiovascular regulation. 2. ATP serves as a co
      transmitter within the sympathetic nervous system, and is also released from
      endothelium and aggregating thrombocytes. ATP acts on P2x purinoceptors on
      vascular smooth muscle cells to induce vasoconstriction. Stimulation of P2y
      purinoceptors on endothelial cells releases endothelium-derived relaxing factors
      and causes vasodilatation. This dual action of ATP may have pathophysiological
      importance by inducing vasospasm at sites of impaired endothelial function and
      thrombus formation. 3. Adenosine is generated by enzymic degradation of ATP. Its
      formation is enhanced during ischaemia. Adenosine inhibits noradrenaline release
      from sympathetic nerve endings, causes vasodilatation via endothelium-dependent
      and endothelium-independent actions, has important anti-arrhythmic properties and
      prevents deleterious sequelae of ischaemia. In humans, adenosine evokes a
      sympatho-excitatory reflex mediated by chemically sensitive receptors and
      afferent nerves in the kidney, heart and forearm. This reflex may be active
      during exercise and ischaemia and, because of its potential adverse consequences,
      it should be considered when developing new therapies to potentiate the anti
      ischaemic actions of endogenous adenosine in humans. Adenosine appears to mediate
      ischaemia-induced pain; a reduced sensitivity to adenosine may underlie silent
      ischaemia. 4. New drugs that interact with adenosine formation or degradation or
      with adenosine receptors are under development. These have potential therapeutic
      application in the treatment of ischaemia and other circulatory disorders.

PMID- 9038588
TI  - Studies on the interaction of T-cells with major histocompatibility complex class
      II antigens.
AB  - 1. Major histocompatibility complex class II antigens have the central role in
      the immune response of 'presenting' antigenic peptide to CD4+ T-cells. This
      interaction with a T-cell's receptor may result in activation, but, if
      recognition occurs without collateral molecular interactions which cause 'co
      stimulation', these T-cells will be tolerized. 2. In the light of current
      interest in muscle cell transplantation, a transformed myoblast, TE671,
      phenotypically comparable to untransformed cells, transfected to express class
      II, was studied as a stable model of antigen presentation by muscle cells. These
      cells failed to activate T-cells but induced tolerance. 3. The DR alpha chain is
      unusual being the only non-polymorphic classical class II polypeptide, raising
      the question of its functional contribution. To this end, several single
      polypeptide constructs were generated with contributions from different class II
      alpha-chains. On this basis, it was established that DR alpha makes significant
      contributions to peptide binding and that its alpha 2 domain is also important in
      T-cell recognition, possibly through CD4 binding. 4. One implication of the lack
      of polymorphism of DR alpha may be that it has a wider range of pairing partners,
      possibly including beta chains of different isotypes. To address this, it is
      planned to use transfectants expressing only a mixed isotype pair to generate T
      cell clones in vitro. These reagents would be useful tools to detect whether such
      mixed pairs exist physiologically. In this paper, the development of a system is
      described which will allow this question to be addressed.

PMID- 9038589
TI  - Neutrophil CD11B expression and neutrophil activation in pre-eclampsia.
AB  - 1. Neutrophil activation was examined in 22 women with pre-eclampsia and 22 age-
      and gestation-matched control subjects using whole-blood flow cytometry to assess
      basal and platelet-activating factor stimulated CD11b and CD18. 2. Basal
      neutrophil CD11b expression was significantly increased in women with pre
      eclampsia compared with normal pregnancy before delivery. A similar non
      significant trend for CD18 was also observed. 3. Before delivery, neutrophil
      CD11b expression increased in a dose-dependent fashion after platelet-activating
      factor stimulation, with the differences between the groups maintained. A similar
      dose-dependent increase in CD18 expression was observed after platelet-activating
      factor. 4. There were no between-group differences in expression of either CD11b
      or CD18 at either 6 weeks or 6 months post partum, either before or after
      platelet-activating factor stimulation. 5. Neutrophil CD11b was positively
      correlated with plasma uric acid (r = 0.44, P = 0.04) in women with pre
      eclampsia, suggesting that the extent of neutrophil activation correlates with
      disease severity. 6. An increase in basal neutrophil CD11b expression in women
      with pre-eclampsia is likely to be an index of neutrophil activation in vivo.
      Neutrophil release of free radicals and proteases may then help perpetuate a
      vicious cycle of endothelial and vascular dysfunction in the placental and
      systemic circulations. The cause of this activation is not known but could
      involve platelet activation, increased production of endothelin-1 or release of
      cytokines. Further studies will be required to elucidate the consequences of
      neutrophil activation in pre-eclampsia.

PMID- 9038590
TI  - Urinary albumin excretion and atherosclerosis in essential hypertension.
AB  - 1. Increased urinary albumin excretion is common in patients with essential
      hypertension and is at least to some extent correlated with prevailing blood
      pressure levels. However, the generalized vascular dysfunction present in
      advanced atherosclerotic disease may independently influence this parameter. 2.
      To evaluate this possibility, we assessed blood pressure, ultrasonographic
      carotid thickness, cardiac mass, minimum forearm vascular resistances, metabolic
      parameters and the angiotensin-converting enzyme genotype in patients with
      untreated essential hypertension and atherosclerotic peripheral vascular disease
      (n = 11). The results were compared with similar data obtained in matched groups
      of patients with uncomplicated hypertension and with normotensive control
      subjects (n = 11 per group). 3. Urinary albumin excretion was higher in
      hypertensive patients with atherosclerosis than in those without complications;
      carotid thickness was higher in atherosclerotic patients and a positive,
      statistically significant correlation existed between this parameter and urinary
      albumin excretion. In the same patient group, systolic blood pressure, fasting
      insulin and triacylglycerol levels were elevated and correlated with urinary
      albumin levels. However, differences in urinary albumin excretion persisted after
      taking into account the influence of those parameters by analysis of covariance.
      The distribution of angiotensin-converting enzyme genotype patterns and values of
      cardiac mass and minimum forearm vascular resistances did not differ
      significantly among the experimental groups. 4. The data suggest that vascular
      status may influence urinary albumin excretion in patients with essential
      hypertension, while confirming the importance of systolic blood pressure levels
      as a determinant of the raised urinary albumin excretion.

PMID- 9038591
TI  - Renal handling of urate and sodium during acute physiological hyperinsulinaemia
      in healthy subjects.
AB  - 1. The renal effects of insulin may play a central role in the association
      between insulin resistance, hypertension and hyperuricaemia. After a 2-h baseline
      period, we investigated the effects of exogenous insulin for 4 h (50 m-units h-1
      kg-1) on fractional renal sodium and urate excretion in 13 healthy subjects,
      using the euglycaemic clamp and lithium clearance technique, and performed a
      control experiment in eight of the subjects. 2. Insulin caused a decline in both
      fractional renal sodium excretion, from 1.13 +/- 0.41% to 0.88 +/- 0.58% (control
      study: 0.81 +/- 0.35 to 1.35 +/- 0.49%; P < 0.001, insulin versus control), and
      fractional renal urate excretion, from 6.72 +/- 1.87% to 5.71 +/- 2.02% (control
      study: 7.03 +/- 2.06 to 7.05 +/- 1.94%; P = 0.085, insulin versus control). The
      changes in fractional renal sodium and urate excretion were positively correlated
      (r = 0.71, P < 0.01). Estimated fractional distal sodium reabsorption increased
      during insulin infusion from 93.7 +/- 2.8% to 96.7 +/- 1.9% (control study: 95.7
      +/- 1.5% to 93.6 +/- 1.1%; P < 0.001, insulin versus control). Estimated
      fractional proximal tubular sodium reabsorption fell from 81.0 +/- 0.5% to 73.7
      +/- 4.7% during insulin infusion, but less in the control study (81.5 +/- 4.3% to
      79.3 +/- 4.8%; P = 0.056, insulin versus control). The changes in fractional
      proximal tubular sodium reabsorption and fractional distal sodium reabsorption
      during insulin infusion were inversely correlated (r = -0.59, P = 0.03). 3.
      During the course of the insulin infusion experiment an inverse correlation
      between the changes in fractional sodium and urate excretion, and the insulin
      mediated glucose disposal, became gradually evident (r = -0.73, P < 0.01, and r =
      -0.71, P < 0.01, respectively; fourth hour of the insulin infusion period). 4. We
      conclude that exogenous insulin acutely decreases renal sodium and urate
      excretion, and that this effect is probably exerted at a site beyond the proximal
      tubule.

PMID- 9038592
TI  - Elevated plasma levels of human adrenomedullin in cardiovascular, respiratory,
      hepatic and renal disorders.
AB  - 1. Adrenomedullin is a potent vasodilating peptide first isolated from
      phaeochromocytoma and adrenal medulla but also found in the heart, lungs and
      kidneys. It may also be a paracrine factor because endothelial and smooth muscle
      cells synthesize adrenomedullin as well as express the receptors. Adrenomedullin
      induces vasorelaxation by activating adenylate cyclase and also by stimulating
      the release of nitric oxide. 2. We have developed a specific radioimmunoassay and
      measured the immunoreactivity of human adrenomedullin in the plasma of 58 male
      subjects: eight with essential hypertension, 12 with heart failure, 10 with
      ascites due to cirrhosis, 12 with chronic renal failure, four with hypoxia due to
      chronic obstructive pulmonary disease and 12 control subjects. 3. Plasma levels
      (mean +/- SEM) in patients with essential hypertension (16.3 +/- 1.9 pmol/l),
      congestive heart failure (17.5 +/- 2.8 pmol/l) and renal failure (17.7 +/- 2.5
      pmol/l) were raised compared with control subjects (7.8 +/- 1.4 pmol/l, P <
      0.05), confirming previous reports. 4. In addition, we observed that plasma
      levels of adrenomedullin were significantly raised in patients with ascites due
      to liver cirrhosis (15.5 +/- 1.9 pmol/l) and chronic obstructive pulmonary
      disease with hypoxia (20.0 +/- 1.5 pmol/l). 5. We concluded that the plasma level
      of adrenomedullin is raised in a variety of diseases.

PMID- 9038593
TI  - Effects of silicon, citrate and the fasting state on the intestinal absorption of
      aluminium in rats.
AB  - 1. The effect of silicon (Si) contained in drinking water and solid food on the
      intestinal absorption of aluminium (Al) remains a matter of debate. The present
      study was designed to readdress this issue in the experimental animal, and to
      examine concomitantly the effects of citrate and the fasting state, respectively.
      2. Three groups of young, non-fasted rats (n = 8 per group) were gavaged by
      solutions containing 3.8 ng of 26Al, 63 ng of 27Al, and either distilled water (<
      0.1 mg/l Si) or commercial mineral water with a medium (6 mg/l) or high (14 mg/l)
      Si concentration. 3. Two other groups of eight non-fasted rats each received the
      same distilled water or high-Si gavage solution, respectively, together with a
      high citrate concentration (62 g/l). In each case the animals had free access to
      drinking water for 5 days before and 2 days after the gavage, containing the same
      Si concentration as in the gavage solution. A sixth group of eight rats was
      gavaged by low-Si, Al and distilled water in the fasted state. 4. The animals
      were killed 48 h after gavage, and blood, tissue and urine samples were collected
      for 26Al measurements by accelerator mass spectrometry. 5. We found that the
      fraction of absorbed 26Al retained in the skeleton (0.025-0.030%) was of the same
      order of magnitude as the fraction excreted in the 48 h urine (0.035-0.037%).
      High Si concentrations in the drinking water failed to depress the 26Al fraction
      absorbed, as estimated on the basis of skeletal accumulation and urinary
      excretion. 6. The administration of citrate-containing fluid enhanced 26Al
      absorption 5- to 10-fold (P < 0.005), but again the Si content of drinking water
      did not interfere. Finally, the intestinal absorption of 26Al was approximately
      15 times higher in the fasted than in the non-fasted state. 7. In conclusion, the
      provision of large amounts of Si in the drinking water failed to modify
      physiological intestinal Al absorption under basal conditions or after its
      stimulation by citrate. However, a prolonged fast greatly enhanced Al absorption,
      compared with the non-fasted state.

PMID- 9038594
TI  - Association of antral mucosal levels of interleukin 8 and reactive oxygen
      radicals in patients infected with Helicobacter pylori.
AB  - 1. Helicobacter pylori infection is characterized by an infiltration of
      neutrophils in the gastric mucosa. Neutrophil activation is an important source
      of reactive oxygen radicals, which cause tissue damage. Studies have shown that
      in Helicobacter pylori-infected patients there is increased mucosal production of
      interleukin 8. However, the role of interleukin 8 in the Helicobacter pylori
      related inflammatory process and its relationship with reactive oxygen radicals
      remains to be clarified. The aims of this study were to investigate if there is
      any association between antral mucosal levels of interleukin 8 and reactive
      oxygen radicals and their relationship to gastric antral inflammation. 2. Fifty
      two patients referred for endoscopy were recruited into the study. Gastric antral
      biopsies were taken for histology, culture and measurement of interleukin 8 and
      chemiluminescence (measuring reactive oxygen radicals). Interleukin 8 was
      measured by ELISA and the result expressed as pg/mg biopsy. Luminol-enhanced
      chemiluminescence was measured as mV min-1 mg-1 biopsy. Antral inflammation was
      assessed by a pathologist in a blinded fashion. 3. Antral mucosal levels of
      interleukin 8 and reactive oxygen radicals were significantly higher in
      Helicobacter pylori-colonized mucosa than in Helicobacter pylori-negative mucosa.
      After the eradication of Helicobacter pylori in patients with duodenal ulcer the
      median values (ranges) of interleukin 8 and reactive oxygen radicals fell from
      1.21 (0.10-2.40) to 0.65 (0.00-1.60) and from 110.0 (10.0-959.0) to 14.5 (0.0
      85.0) respectively. There was a positive correlation between interleukin 8
      concentration and chemiluminescence response in the antral mucosa (r = 0.72). A
      higher interleukin 8 concentration was associated with greater neutrophil
      infiltration (r = 0.72) and mononuclear cell infiltration (r = 0.55); the
      magnitude of the chemiluminescence response was also positively associated with
      neutrophil (r = 0.77) and mononuclear cell infiltration (r = 0.59). 4.
      Interleukin 8 concentration is associated with an infiltration of neutrophils and
      mononuclear cells and is correlated with the production of reactive oxygen
      radicals in antral gastric mucosa infected with Helicobacter pylori. These
      findings suggest that interleukin 8 may be important in attracting and activating
      phagocytes to release reactive oxygen radicals, thereby causing mucosal damage.

PMID- 9038595
TI  - Brisk walking reduces calcaneal bone loss in post-menopausal women.
AB  - 1. This study examined the influence of brisk walking on skeletal status in post
      menopausal women. 2. Subjects were 84 healthy women aged 60-70 years. Who were
      previously sedentary and at least 5 years post-menopausal. Subjects were randomly
      assigned to walking (n = 43) and control (n = 41) groups. Walkers followed a 12
      month, largely unsupervised programme of brisk walking. The bone mineral density
      of the lumbar spine, femoral neck and calcaneus and broadband ultrasonic
      attention of the calcaneus were measured at baseline and after 12 months. 3.
      Forty control subjects and 38 walkers completed the study. Walkers built up to
      20.4 +/- 3.8 min/day (mean +/- SD) of brisk walking. Body mass increased in
      control subjects relative to walkers [mean change (SE) +0.9 (0.3) and -0.1 (0.3)
      kg respectively; P = 0.04]. Predicted maximum oxygen uptake increased in walkers
      by 2.1 (0.9) ml min-1 kg-1 (P = 0.02). Bone mineral density in the lumbar spine
      and calcaneus fell in control subjects [-0.005 (0.004) and -0.010 (0.004) g/cm2,
      respectively] but not in walkers [+0.006 (0.004) and +0.001 (0.004) g/cm2]. The
      difference in response between groups was significant in the calcaneus (P = 0.04)
      but not in the lumbar spine (P = 0.08). Mean femoral neck bone mineral density
      did not change significantly in either group, although changes in walkers were
      related to the amount of walking completed (r = 0.51, P = 0.001). The change in
      broadband ultrasonic attenuation of the calcaneus differed between groups
      [control subjects, -3.7 (0.8); walkers, -0.7 (0.8) dB/MHz; P = 0.01]. 4. Walking
      decreased bone loss in the calcaneus and possibly in the lumbar spine. It also
      improved functional capacity and enabled walkers to avoid the increase in body
      mass seen in control subjects.

PMID- 9038596
TI  - Assessment of postural differences in regional pulmonary perfusion in man by
      single-photon emission computerized tomography.
AB  - 1. With the advent of single-photon emission computerized tomography, controversy
      has arisen with regard to the significance of gravitational influences on
      regional pulmonary perfusion (Qr) in the supine versus prone postures. We
      investigated the dorsal-ventral distributions of Qr in prone (n = 5) and supine
      (n = 5) normal subjects, as assessed by single-photon emission computerized
      tomography after intravenous injection of technetium-99m-labelled macroaggregated
      albumin at end-tidal expiration. Reconstructed serial (one pixel thickness)
      coronal sections were traced on a computer screen, to yield the encompassed
      radioactive counts and number of pixels per each image. Coronal section data
      (expressed as mean radioactive counts/pixel) were expressed in a 'profile' and
      normalized to the maximum coronal section of each lung (% maximum). 2.
      Coefficients of variation and linear regression slopes for the prone versus
      supine profiles for left and right lungs were not statistically different
      (unpaired Student's t-test). The coronal section with maximum Qr was identified
      in the more dependent lung regions and, hence, affected by gravity. 3. We
      conclude that, in contrast to previous canine models, which have suggested
      postural differences in dorsal-ventral perfusion gradients, in normal man gravity
      primarily determines the non-dependent to dependent distribution of Qr. We
      speculate that interspecies differences in physiology may be teleological and
      related to the different perfusion demands of the quadruped compared with upright
      man.

PMID- 9038597
TI  - Plasma RRR-alpha-tocopherol concentrations are lower in smokers than in non
      smokers after ingestion of a similar oral load of this antioxidant vitamin.
AB  - 1. Using deuterium-labelled alpha-tocopherol (vitamin E), the plasma kinetics of
      alpha-tocopherol derived from supplemental RRR-alpha-tocopherol and RRR-alpha
      tocopheryl acetate were determined in asymptomatic individuals who smoke and, for
      comparison, in a group of healthy non-smokers. 2. Venous blood samples were
      withdrawn 6, 12 and 27 h after the oral administration of a gelatin capsule
      containing an equimolar mixture of RRR-alpha-tocopheraol and RRR-alpha-tocopheryl
      acetate. Plasma concentrations of endogenous and administered forms of alpha
      tocopherol were determined by a combination of HPLC and GC-MS. 3. Both the free
      phenol and the acetate ester concentrations of alpha-tocopherol were lower in
      smokers than in non-smokers: 0.99 versus 1.60 (P < 0.05) and 0.66 versus 1.49 (P
      < 0.05) mumol/mmol cholesterol for RRR-alpha-tocopherol and RRR-alpha-tocopheryl
      acetate respectively. The highest concentation of alpha-tocopherol derived from
      administered RRR-alpha-tocopherol and its acetate ester were observed in plasma
      at 12 h (compared with 6-h and 27-h measurements) in most subjects. 4. Although
      the two forms of alpha-tocopherol were administered in equal doses, plasma from
      smokers contained significantly higher concentrations of RRR-alpha-tocopherol
      derived from the free phenol form than from the acetate form (0.99 versus 0.66
      mumol/mmol cholesterol, P < 0.05, 12 h). Non-smokers did not exhibit preferential
      uptake of either form of vitamin E. 5. These results suggest that individuals who
      smoke have either a reduced ability to absorb alpha-tocopherol, particularly when
      it is presented as the acetate ester, or increased clearance of newly absorbed
      alpha-tocopherol compared with non-smokers.

PMID- 9038598
TI  - Dietary fish oil reduces survival and impairs bacterial clearance in C3H/Hen mice
      challenged with Listeria monocytogenes.
AB  - 1. To investigate the effect of dietary fat source on host resistance to
      intracellular pathogens, weanling female C3H/Hen mice were fed one of three
      experimental diets containing, 20% by weight, lard, soybean oil or 17% menhaden
      fish oil plus 3% corn oil. After 4 weeks, survival of mice (n = 12/treatment
      group) injected intraperitoneally with 2 x 10(6) colony forming units of live
      Listeria monocytogenes was determined. In a second study, bacterial clearance
      from the liver and spleen at 2, 4 and 7 days post-challenge was determined (n =
      8/treatment group). 2. We found that the survival of mice fed the diets with
      soybean oil or menhaden fish oil was significantly lower than those fed lard (P <
      0.05). Survival rates were 58% (7/12), 33% (4/12) and 100% (12/12), respectively,
      for mice fed soybean oil, menhaden fish oil and lard. In the second study, mice
      fed menhaden fish oil had approximately 1 log10 greater bacteria in their spleens
      at day 4 than mice fed lard or soybean oil (P < 0.001). There were no significant
      treatment differences in the number of bacteria recovered from liver samples. 3.
      In summary, dietary fat source significantly affects murine resistance to
      Listeria, with diets rich in n-3 polyunsaturated fatty acids, such as from fish
      oil, having the most detrimental effect.

PMID- 9038599
TI  - Chemotherapy of high-grade gliomas: beginning of a new era or the end of the old?

PMID- 9038600
TI  - Is intra-arterial chemotherapy worthwhile in the treatment of patients with
      unresectable hepatic colorectal cancer metastases?
AB  - Regional chemotherapy, from a theoretical and pharmacological stand point, would
      seem to offer significant advantage over systemic therapy for the treatment of
      hepatic metastatic colorectal cancer patients. Clinical experience has shown us
      that the technique itself is fraught with practical problems, but over the years,
      specialist centres have learned to overcome many of these, making the technique
      safer and minimising the possibility of complications and toxicity. As a
      consequence, there is no doubt that high response rates can be achieved with HAI
      fluoropyrimidines. However, randomised data have only been obtained from small
      numbers of patients in suboptimally designed trials and, to date, true patient
      benefit in terms of either survival or quality of life has not been adequately
      demonstrated. In parallel with the U.S. Intergroup study, the U.K.-based MRC
      phase III clinical trial of regional versus systemic 5-FU/FA warrants urgent
      support and we would welcome collaboration with interested European and American
      centres. The outcome of this trial will fully define the role of HAI chemotherapy
      in the management of unresectable hepatic metastatic colorectal cancer, in the
      context of modern, modulated 5-FU.

PMID- 9038601
TI  - Inheritance and susceptibility to tumours of the large bowel: a new
      classification of colorectal malignancies.

PMID- 9038602
TI  - Intra-epithelial and invasive cervical neoplasia during HIV infection.
AB  - Patients affected by human immunodeficiency virus (HIV) infection present an
      elevated risk of developing cancer. In the last 10 years, the relationship
      between human papilloma virus (HPV) infection and female cervical intra
      epithelial neoplasia (CIN) has been established. Several studies have described
      an increased prevalence of both cervical HPV infection and CIN among HIV-positive
      women compared to HIV-negative ones. A high recurrence rate of CIN after standard
      treatment has been noted in HIV-infected women and the severity of these lesions
      seems to be inversely correlated to immune function. Taking into account these
      data, the Centers for Disease Control (CDC) since 1993 have included invasive
      cervical carcinoma among the AIDS-defining conditions. Once cervical cancer
      develops in HIV-positive women, the disease may be aggressive and less responsive
      to treatment. A primary means by which HIV infection may influence the
      pathogenesis of HPV-associated cervical pathology is by molecular interaction
      between HIV and HPV genes. Although these have not been well defined, an
      upregulation of HPV E6 and E7 genes expression by HIV proteins (such as tat) has
      been postulated by some authors. Cervical cytology appears to be adequate as a
      screening tool for the cervical intra-epithelial neoplasia in HIV-positive women,
      but the high recurrence rate and multifocality of this disease reinforces the
      need for careful evaluation and follow-up of the entire anogenital tract in these
      women. Probably in the next few years, cervical tumours will represent one of the
      most frequent complications of HIV infection, a part of progression through AIDS.
      This points to a need for greater interdisciplinary co-operation for a best
      disease definition and for the development of effective prevention measures.

PMID- 9038603
TI  - Treatment of recurrent malignant supratentorial gliomas with ifosfamide,
      carboplatin and etoposide: a phase II study.
AB  - Thirty-six patients previously treated with surgery, radiation therapy and
      chemotherapy with a nitrosourea for malignant supratentorial gliomas received a
      combination of ifosfamide, carboplatin and etoposide (ICE) at tumour progression.
      Carboplatin and etoposide were both given at a dose of 75-100 mg/m2/day for 3
      days, whereas ifosfamide doses ranged from 750 mg/m2/day to 1500 mg/m2/ day for 3
      days, according to haematological tolerance. Treatment was repeated every 4
      weeks. A minimum of three courses was required to evaluate the response unless
      the patient had rapid tumour progression. Grade III and IV haematological
      toxicity occurred in 15 patients (42%) and was lethal in one patient. Grade II
      hepatic toxicity was observed in one patient. Five complete (CR) and five partial
      responses (PR) were noted. 9 patients had stable disease (SD) after a minimum of
      three courses. CR + PR + SD was 53% (19/36). The median time to tumour
      progression (MTTP) was 13 weeks. Median survival (MST) was 29 weeks (44 weeks for
      R + S patients and 17 weeks for patients with progressing disease). This study
      suggests that the ICE combination is active in recurrent supratentorial malignant
      gliomas after failure of surgery, radiation therapy and chemotherapy, but at the
      cost of substantial haematological toxicity.

PMID- 9038604
TI  - The Charing Cross Hospital experience with temozolomide in patients with gliomas.
AB  - Temozolomide, a new oral cytotoxic agent, was given to 75 patients with malignant
      gliomas. The schedule used was for the first course 150 mg/m2 per day for 5 days
      (i.e. total dose 750 mg/m2), escalating, if no significant myelosuppression was
      noted on day 22, to 200 mg/m2 per day for 5 days (i.e. total dose 1000 mg/m2) for
      subsequent courses at 4-week intervals. There were 27 patients with primary
      disease treated with two courses of temozolomide prior to their radiotherapy and
      8 (30%) fulfilled the criteria for an objective response. There were 48 patients
      whose disease recurred after their initial surgery and radiotherapy and 12 (25%)
      fulfilled the criteria for an objective response. This gave an overall objective
      response rate of 20 (27%) out of 75 patients. Temozolomide was generally well
      tolerated, with little subjective toxicity and predictable myelosuppression.
      However, the responses induced with this schedule were of short duration and had
      relatively little impact on overall survival. In conclusion, temozolomide given
      in this schedule has activity against high grade glioma. However, studies
      evaluating chemotherapy in primary brain tumours should include a quality-of
      life/performance status evaluation in addition to CT or MRI scanning assessment.

PMID- 9038605
TI  - Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas.
AB  - Paraffin embedded tissue of 84 oligodendrogliomas (63 primary tumours, 21
      recurrences), 21 glioblastomas with oligodendroglial growth pattern (15
      primaries, 6 recurrences) and 17 mixed gliomas was investigated for the presence
      of mutations in exons 5-9 by means of single stranded conformation polymorphism
      (SCCP), temperature gradient gel electrophoresis (TGGE) and direct DNA
      sequencing. In parallel, p53 protein accumulation was determined by means of
      immunohistochemistry. The percentage of mutations was found to be higher than
      previously reported (6 of 44 grade II oligodendrogliomas, 4 of 19 grade III
      oligodendrogliomas, 4 of 15 glioblastomas). In 4 cases, the mutations lead to
      distinct changes in the primary or secondary structure of the protein (cysteine-
      >tyrosine, proline-->leucine) and were associated with marked accumulation of p53
      protein. A significant correlation between p53 protein accumulation and TP53 gene
      aberrations was found (P < 0.001), although p53 protein accumulation was detected
      more often than TP53 gene anomalies, indicating that factors other than TP53 gene
      mutation may also lead to a p53 protein accumulation in the tumour cells. A
      significant correlation was found for p53 protein accumulation and tumour grade
      but not TP53 gene mutations. In conclusion, evaluation of p53 protein
      accumulation reflected the clinical course of oligodendrogliomas better than the
      mere presence of TP53 gene mutations.

PMID- 9038606
TI  - The cost-effectiveness of navelbine alone or in combination with cisplatin in
      comparison to other chemotherapy regimens and best supportive care in stage IV
      non-small cell lung cancer.
AB  - An economic evaluation was undertaken, using data from European and Canadian
      randomised controlled trials of chemotherapy in advanced non-small cell lung
      cancer (NSCLC), to determine the cost and cost-effectiveness of single-agent
      vinorelbine (Navelbine, NVB) therapy and NVB in combination with cisplatin (NVB
      P) compared to vindesine in combination with cisplatin (VDS-P), standard regimens
      including VP-16-cisplatin (VP-16-P) and vinblastine-cisplatin (VLB-P) and best
      supportive care (BSC). The Population Health Model (POHEM) developed by
      Statistics Canada was used to model the cost of care per patient, the total
      burden of cost to the Canadian healthcare system and the cost-effectiveness of
      the therapeutic interventions relative to BSC and to standard chemotherapy
      regimens, expressed as the cost per life year gained (LYG). Based on this
      analysis, VLB-P proved to be the most cost-effective chemotherapy regimen
      relative to BSC, as it increased average survival by 0.27 years while reducing
      costs by $3265 per case. NVB-P increased survival to a greater degree (0.44
      years/patient) while inpatient administration increased costs by $2451 per case,
      for a cost-effectiveness ratio of $5551 per LYG. Outpatient administration, which
      reduced the cost of care per case by $473, was shown in the model to be the most
      cost-effective way to administer this regimen. Relative to VP-16-P and VLB-P,
      outpatient NVB-P regimen proved to be cost-effective at $7902 and $16404 per LYG,
      respectively. Based on our estimates, a variety of chemotherapy regimens,
      including outpatient NVB-P, are cost-effective in the management of advanced
      (Stage IV) NSCLC and competitive with some commonly used healthcare
      interventions. Therefore, cost and cost-effectiveness should not be barriers to
      the utilisation of NVB-P therapy in Canada.

PMID- 9038607
TI  - Unknown primary carcinoma: randomised studies are needed to identify optimal
      treatments and their benefits.
AB  - This is a retrospective review of 101 patients with unknown primary carcinoma
      (UPC) treated between 1989 and 1994, on whom data were collected prospectively.
      92 patients received platinum-based chemotherapy and 9 had single agent 5
      fluorouracil (5-FU). In the platinum group, an objective response rate of 37.2%
      was seen, with a median duration of 4.5 months (range 1.9-17.5). There were no
      responses with 5-FU alone, while median survival was 6.4 months and was not
      different from the platinum group (P = 0.09). Considerable symptomatic resolution
      was noted, although the contribution of chemotherapy alone to this is difficult
      to define. The impact of tumour response on quality of life and survival in UPC
      requires further elucidation in prospective studies with a "best supportive care'
      arm. The superiority of platinum-based treatments reported in selected subgroups
      cannot be applied to the whole spectrum of UPC.

PMID- 9038608
TI  - Complications of an implantable venous access device (Port-a-Cath) during
      intermittent continuous infusion of chemotherapy.
AB  - In 149 patients, treated with intermittent continuous infusion of different
      chemotherapeutic agents, 169 Port-a-Caths were implanted by qualified surgeons
      and residents in training. The peri- and postoperative complications of
      implantation of the Port-a-Cath system and the complications during treatment
      were retrospectively analysed. The Port-a-Cath was in situ for a total of 36247
      days (median 181, range 1-1332). Of the 169 catheters, major complications
      occurred during treatment, with infection in 4 patients (2.4%), occlusion in 3
      (1.8%), thrombosis in 8 (4.7%), extravasation in 8 (4.7%) and migration in 3
      (1.8%). The peri- and postoperative complication rate was low, although
      pneumothorax occurred in 6 patients (3.6%). In 25 patients (14.8%) the Port-a
      Cath had to be explanted due to complications. It can be concluded that
      continuous infusion of chemotherapy via a Port-a-Cath system is a relatively safe
      procedure, although major complications do occur. The experience of the surgeon
      could not be related to the complications.

PMID- 9038609
TI  - Surveillance versus adjuvant chemotherapy in stage I non-seminomatous testicular
      cancer: a decision analysis.
AB  - In stage I non-seminomatous testicular cancer, the decision between surveillance
      and adjuvant chemotherapy rests heavily upon the valuation of quality of life.
      Decision analysis was used to assess at what relapse rate adjuvant chemotherapy
      is preferred when patients' and clinicians' evaluations are considered.
      Probabilities were obtained from the literature and from experts. Evaluations of
      the disease states were obtained from patients (n = 68) and clinicians (n = 50).
      Results from the model were compared with a treatment preference question, asking
      for the relapse rate directly. Adjuvant chemotherapy was preferred at relapse
      rates above 50% when patient evaluations were used. The evaluations of the
      disease states had a strong impact on the decision. Using clinician evaluations,
      adjuvant chemotherapy was preferred at relapse rates above 73%. The relapse rates
      from the treatment preference question were lower: 46% for patients and 35% for
      clinicians. The results indicate that when patient preferences are accounted for,
      adjuvant chemotherapy should be considered more often.

PMID- 9038610
TI  - The cognitive effects of recombinant interleukin-2 (rIL-2) therapy: a controlled
      clinical trial using computerised assessments.
AB  - It has been suggested that patients undergoing treatment with recombinant
      interleukin-2 (rIL-2) may develop cognitive impairment. To evaluate these
      effects, 17 patients with advanced colorectal cancer took part in a randomised,
      parallel group study of rIL-2 with chemotherapy (5-fluorouracil and leucovorin)
      and chemotherapy alone. Assessments were carried out daily whilst patients were
      in hospital and regularly between cycles of treatment using state-of-the-art
      computerised cognitive assessment, as well as traditional psychometric tests.
      Rigorous discontinuation criteria were applied to ensure that the effect of time
      related variables did not influence the results. One patient developed repeated
      transient psychotic episodes associated with rIL-2 infusions and another
      regularly became confused. Computerised cognitive assessments revealed that
      immunochemotherapy produced significant impairment in various tasks, especially
      reaction time, picture recognition and vigilance. These effects were not due to
      sleep deprivation or pyrexia. For most patients, cognitive functioning was
      restored to the baseline level within 10 days following the cessation of rIL-2.
      In conclusion, during infusions of rIL-2, some patients experience severe
      confusion and amnesia which resembles some of the major cognitive impairments
      associated with dementias such as Alzheimer's disease. Computerised cognitive
      assessment using the Cognitive Drug Research system provides a feasible,
      sensitive and reliable method of evaluating cognitive changes in patients with
      cancer. It could usefully be included in quality of life assessments in clinical
      trials where treatment-related cognitive changes need to be evaluated.

PMID- 9038611
TI  - Quality of life: perception of lung cancer patients.
AB  - An investigation was carried out to examine what quality of life means to lung
      cancer patients. 200 patients with either lung cancer (108) or chronic
      respiratory disease (92) were interviewed using a short open-ended questionnaire.
      They were asked to define quality of life in general, identify what they
      considered to be a good quality of life for themselves and to rank the relative
      importance attached to each nominated item. A content analysis was carried out
      and patients' responses were categorised into eight items. These were: ability to
      do what one wants to do/work, enjoyment of life, family life, financial security,
      happiness, health, living longer and social life/leisure activities. Of these,
      health (42%), enjoyment of life (25%) and family life (24%) were the three most
      nominated items as definition of quality of life in general. Patients perceived a
      good quality of life for themselves differently. Family life (58%), health (51%)
      and social life (43%) were found to be the most nominated components of a good
      quality of life for the patients. Overall, patients ranked family life and health
      as the first or second most important factors. There were no significant
      differences between cases and controls. The study results are challenging and
      serve to remind us that the term quality of life is misused in many studies. Most
      existing measures do not encompass the wider aspects of quality of life
      identified here, but rather concentrate on the "health-related" aspects of
      quality of life. To achieve this, the research into the best ways of measuring
      and assessing quality of life must continue to seek individual values and
      preferences and how these can be applied in a simple way in clinical studies.

PMID- 9038612
TI  - Etoposide for the treatment of paediatric tumours: what is the best way to give
      it?
AB  - Etoposide is one of the most important drugs available for the treatment of
      paediatric malignancies. Although there is evidence of schedule dependency for
      etoposide therapy in adults with small-cell lung cancer, the relevance of this
      observation to childhood cancers is uncertain. Prolonged parenteral or oral
      etoposide therapy has not yet shown a clear-cut advantage over intermittent
      treatment, and there are still no data to show that the administration of
      etoposide as a short intravenous (i.v.) daily infusion for 5 days does not
      represent acceptable therapy for primary disease. The pharmacokinetic variability
      seen with etoposide argues strongly for the use of pharmacologically guided
      dosing, and the introduction of etoposide phosphate will simplify both parenteral
      etoposide administration and the future evaluation of alternative etoposide
      schedules. Although the impact of molecular and cellular pharmacological
      investigations on the clinical use of etoposide has yet to be felt, the tools to
      perform these studies are now available and prospective trials can be designed.
      Such studies, performed in the setting of a pharmacologically guided trial to
      ensure control over pharmacokinetic variability, should identify the best way of
      treating children with etoposide.

PMID- 9038613
TI  - Screening for neuroblastoma in late infancy by use of EIA (enzyme-linked
      immunoassay) method: 115000 screened infants in Austria.
AB  - The aim of this study was to investigate the feasibility of a neuroblastoma
      screening programme for children in late infancy, based on collaboration of
      general paediatricians and practitioners in Austria, using the technique of
      enzyme-linked immunoassay (EIA) for biochemical analyses. Analysis of
      catecholamine metabolites in spot urine samples by EIA with high performance
      liquid chromatography as a backup was undertaken. Austrian infants (median age
      8.7 months) were screened. Overall compliance was 30%. The EIA method had a high
      rate (6.7%) of false-positive results. 28 infants were admitted to hospital. In
      15 cases, neuroblastoma was found (four stage 1, five stage 2B, six stage 3). The
      EIA method can be used for neuroblastoma screening, but requires a backup
      analytical technique in order to avoid unnecessary hospital admissions. The stage
      distribution and biological features of neuroblastomas diagnosed by screening at
      a later age are different from those detected by earlier screening. Screening in
      late infancy might be of more benefit than early screening.

PMID- 9038614
TI  - Primary gastric non-Hodgkin's lymphoma stage IE and IIE.
AB  - The aim of this study was to evaluate retrospectively the different treatment
      approaches and outcome of patients with stage IE and IIE gastric non-Hodgkin's
      lymphoma in a cancer registry. Between 1982 and 1992, the Comprehensive Cancer
      Centre South (CCCS), Eastern Section, The Netherlands, registered, in a
      population of 1 million people, a total of 81 cases of gastric lymphoma stage IE
      and IIE (43 men and 38 women). Median age was 69.7 years (range 30.4-88.1).
      According to the Working Formulation, the malignancy grade was: 9 low, 55
      intermediate and 14 high. According to the MALT classification, the malignancy
      grade was: 38 low and 40 high. Grade was unknown in 3 patients. Patients received
      the following treatment modalities: surgery alone (n = 22), locoregional
      radiotherapy without (n = 12) or with (n = 13) surgery; or systemic chemotherapy
      alone (n = 10) or with radiotherapy and/or surgery (n = 18). No treatment was
      given or recorded in 6 patients. For stage IE, 5-year actuarial survival and
      relapse-free survival rates were, respectively, 76 and 64% in 18 patients who
      received only surgery; 70 and 67% in 17 patients given locoregional treatment
      (radiotherapy with or without surgery), and 76 and 62% in 13 patients given
      systemic treatment (chemotherapy alone or with radiotherapy and/or surgery).
      Radiotherapy as sole treatment seemed to be as effective as other treatment
      modalities in achieving local and abdominal control. For stage IIE, none of the 4
      patients who were treated with surgery alone survived 5 years. The 5-year
      actuarial survival and relapse-free survival rates of 8 patients who received
      radiotherapy with or without surgery were, respectively, 25 and 17% and 49 and
      33%, for 14 patients given systemic therapy (chemotherapy alone and/or
      radiotherapy/surgery). In stage IIE, local, abdominal as well as distant relapse
      were more common, irrespective of treatment modality. In the multivariate
      analyses, stage (P = 0.002), grade (P = 0.02), age (P = 0.04) and gender (P =
      0.04) were significant prognostic factors. This report on a limited number of
      patients shows that the outcome of patients with stage IIE gastric lymphoma is
      much worse than for patients with stage IE. Grade, age, gender and particularly
      stage are much stronger indicators for survival than different modes of
      treatment. Systemic therapy might improve outcome for stage IIE, but not for
      stage IE, for which radiotherapy alone seems a good option.

PMID- 9038615
TI  - Tumour necrosis factor and interferon are selectively cytostatic in vitro for
      hormone-dependent and hormone-independent human breast cancer cells.
AB  - Since experimental studies have shown that tumour necrosis factor-alpha (TNF
      alpha) has potent anti-tumour activity that can be potentiated with cytokines, we
      tested the efficacy of TNF-alpha with interferon-gamma (IFN-gamma) on different
      human breast cancer cell lines, particularly comparing hormone-dependent and 
      independent phenotypes. TNF-alpha inhibited the growth of hormone-dependent human
      MCF-7, ZR-75-1 and T47-D breast cancer cells with a half maximal concentration of
      0.25 nM. In contrast, the growth of hormone-independent cells MDA-MB-231 and
      HS578T was not affected by TNF-alpha alone, but a synergistic inhibition was
      observed when using IFN-gamma and TNF-alpha together. The mRNA for the proto
      oncogene C-MYC, as an intracellular indicator of cell activation, was
      significantly increased in MCF-7 cells in the presence of TNF-alpha. In MDA-MB
      231 cells this mRNA was increased only in the presence of both TNF-alpha and IFN
      gamma, without a change in the number of surface TNF receptors. These findings
      indicate that TNF-alpha treatment in combination with IFN-gamma may provide a
      successful approach to overcome the cellular heterogeneity of advanced breast
      tumours.

PMID- 9038616
TI  - Analysis of O6-methylguanine-DNA methyltransferase mRNA in fine needle biopsies
      from human melanoma metastases by reverse transcription and polymerase chain
      reaction.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein, which
      removes alkyl groups from the O6 atom of guanine residues. Tumour cells which
      lack MGMT are sensitive to cytostatic drugs such as dacarbazine (DTIC), whose
      active species bind to this site. To explore whether analyses of MGMT expression
      can be used as a predictive test for clinical sensitivity to DTIC in melanomas,
      we developed a method to assay MGMT mRNA levels in cells obtained by fine needle
      aspiration biopsies of metastases. cDNA was synthesised from mRNA prepared from
      biopsy material. Polymerase chain reaction was performed using primers
      complementary to MGMT cDNA and to beta-actin, which served as an internal
      control. Analyses of 44 biopsies from 35 patients showed a considerable variation
      in MGMT mRNA, with 15 samples (34%) lacking detectable mRNA. In 6 out of 8
      patients in whom more than one tumour was analysed, separate metastases had
      different levels of MGMT mRNA. There was no correlation between MGTM activity
      studied by a biochemical assay and MGMT mRNA levels when these were compared in
      10 surgical biopsies.

PMID- 9038617
TI  - Cisplatin combined with the new cisplatin-procaine complex DPR: in vitro and in
      vivo studies.
AB  - The administration of combinations of platinum compounds is considered as a
      useful alternative therapeutic strategy to avoid the complications of toxic
      events during cancer chemotherapy in order to obtain a therapeutic advantage. On
      the basis of previous in vitro and in vivo findings, suggesting an antitumour
      activity of the new cisplatin-derived compound cis-diamminechloro-[2
      (diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride
      monohydrate (DPR), we investigated the effectiveness of the combination of
      cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either
      sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076
      reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388
      leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The
      contemporaneous exposure in vitro to both platinum compounds gave a significantly
      higher cell growth inhibition than that expected on the basis of dose-response
      curves for single agents in all tumour models tested. In vivo, the combinations
      of DDP plus DPR elicited significant enhancement over the activity of the drugs
      alone both in the ascitic and solid P388 models. The combined treatment of 10
      mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with
      10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined
      application of DDP and DPR was also very effective in the solid cisplatin
      resistant L1210/DDP model, inducing a significant reduction in the volume of
      tumour. A therapeutic advantage was achieved with combination treatments that had
      no effect on platinum-mediated body weight loss and were generally well tolerated
      by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment
      with DDP plus DPR proved to have a higher efficacy against this tumour model
      compared to that observed after the combined treatment with DDP and carboplatin.
      In summary, the combination of DDP and DPR showed a therapeutic advantage over
      single drug treatment and has demonstrated promise at the preclinical level in
      its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

PMID- 9038618
TI  - Examination of multidrug resistance in cell lines and primary breast tumours by
      flow cytometry.
AB  - The aim of this study was to measure multidrug resistance (MDR) by flow cytometry
      and quantify the expression of P-glycoprotein (using antibody) glutathione
      transferase (using alpha-GSTpi antibody) in alpha-JSB-1 and alpha-GSTpi of a
      series of cell lines and primary breast cancers, and to assess the relationship
      between these MDR proteins and a selection of oncogene and prognostic markers in
      breast cancer. Flow cytometry was performed using permeabilised cells stained
      with fluorescent antibodies using well-established methods. Antibody staining was
      confirmed for JSB1, but not GSTpi by use of known positive and negative controls.
      No correlation was seen when comparing the number of molecules of alpha-JSB-1
      with alpha-GSTpi (P = 0.1, r2 = 0.4, n = 14) using a selection of cell lines.
      Examination of 45 breast tumours for expression of JSB-1 and GSTpi revealed a
      significant association between these two antibodies (P < 0.00001, r2 = 0.5, n =
      45). On examining the breast tumours, alpha-JSB-1 showed a positive association
      with c-erbB-2 (P = 0.003), c-myc (P = 0.0004) and c-jun (P = 0.02) but not ER or
      EGF-R expression. alpha-GSTpi showed a positive association with c-erbB-2 (P =
      0.03) and c-myc (P = 0.0004) but not ER, EGF-R or c-jun. Flow cytometric MDR
      levels were not related to tumour grade or axillary node status. In solid
      tumours, a relationship between the two antibodies used has been clearly
      demonstrated, however, specificity of alpha-GSTpi is questioned. Both antibodies
      show an association with c-erbB-2, which is associated with poor prognosis and
      with c-myc which is involved in cell cycling and differentiation. Monitoring MDR
      markers (Pgp) using this methodology may be useful for evaluation of prognosis in
      breast cancer.

PMID- 9038619
TI  - Enhanced invasiveness of tumour cells after host exposure to heavy metals.
AB  - The invasiveness of tumour cells to heavy metal-exposed host cells or tissues was
      investigated. Human fibrosarcoma cell invasion of heavy metal-treated fibroblast
      or endothelial cell was enhanced in a treatment-time-dependent manner although
      tumour cell attachment to host cells was not affected. This enhancement was
      correlated with an increase in metallothioneins in the cytosol of fibroblasts or
      endothelial cells. Mouse melanoma cell invasion of organ samples obtained from
      syngeneic mice who had been administered heavy metals was also enhanced. The
      results suggest that heavy metal-induced metallothioneins serve as a host-derived
      factor in malignant disease and closely relate to metastasis.

PMID- 9038620
TI  - Oestrogen and progesterone receptors in gastrointestinal cancer cell lines.
AB  - Expression of sex steroid receptors by gastrointestinal (GI) tumours may indicate
      a role for hormonal manipulation in their management. A panel of seven
      established cell lines derived from primary human GI tumours were assayed for
      oestrogen and progesterone receptor (ER and PgR) expression by ligand binding,
      immunocytochemistry and enzyme-immunoassay methods. It was possible to
      demonstrate very low levels of both ER and PgR in the GI cell lines using enzyme
      immunoassay (EIA), with levels of PgR generally higher than those for ER. Neither
      ER nor PgR were detected in cytosols made from the GI cell lines in a classical
      dextran coated charcoal ligand binding assay. Similarly, immunohistological
      analysis (Abbott ERICA, PgRICA) of cultured cell preparations or of frozen and
      paraffin sections of xenograft tumour failed to demonstrate receptors. This
      confirms that low PgR levels are measurable by EIA in GI tumour cell lines.
      Upregulation of PgR expression in tumours by exposure to oestradiol in vitro was
      not observed.

PMID- 9038621
TI  - A pilot study to evaluate paclitaxel (Taxol) as primary medical treatment for
      patients with inoperable stage III and IV breast carcinoma.
AB  - The activity of paclitaxel has been extensively investigated in previously
      treated patients with metastatic breast carcinoma. We evaluated the activity of
      paclitaxel as primary medical therapy in patients with stage III and IV breast
      carcinoma, 6 female patients were recruited with no previous history of surgery,
      radiotherapy or chemotherapy. Paclitaxel was administered as a 3-h infusion at a
      dose of 225 mg/m2 repeated every 3 weeks weekly to a maximum of 10 cycles. 2
      patients achieved a complete response, one of whom had a normal trucut biopsy of
      the affected breast 6 months after discontinuation of chemotherapy and
      radiotherapy and a normal mammogram at 17 months. 3 patients achieved a partial
      response and one stabilised. The patients received between four and ten cycles of
      chemotherapy. Paclitaxel at this dose was associated with toxicity including
      alopecia, stomatitis, nausea and diarrhoea. Moderately severe neutropenia
      occurred in 4 patients, 2 requiring antibiotics but was of short duration and did
      not necessitate a dose reduction for subsequent courses. Paclitaxel has shown
      activity as primary medical therapy in patients with inoperable breast carcinoma
      at presentation at this dosage and schedule. One patient achieved a complete
      response and avoided surgery altogether and all 6 patients had their primary
      tumour downgraded. It may be indicated as a single agent in this context or in
      combination with other drugs with proven activity in breast carcinoma.

PMID- 9038622
TI  - Elevated germ cell markers in carcinoma of uncertain primary site do not predict
      response to platinum based chemotherapy.
AB  - We carried out a retrospective review of the medical records of patients with
      metastatic carcinoma of unknown primary and either raised alpha fetoprotein (AFP)
      or beta human chorionic gonadotrophin (beta HCG) over a period of 6 years at
      three teaching hospital oncology units to assess response to platinum based
      chemotherapy. 15 patients were identified who fitted these criteria. Of these, 3
      received no treatment because of poor functional status, 2 patients received only
      radiotherapy for symptomatic disease and died within 3 months of diagnosis and 1
      patient died 2 weeks after diagnosis having received his first cycle of cisplatin
      based chemotherapy. 9 patients received at least 2 cycles of chemotherapy. A
      complete tumour response was seen in only one patient who presented with midline
      lymphadenopathy and remains disease-free 46 months after treatment. This
      presentation was consistent with disease already known to herald platinum
      sensitivity. In the other 8 patients, there was only one partial response that
      lasted 2 months. The median survival for this group of 9 patients was 4.5 months
      (range 3 to > 46 months). Our data do not support the postulate that elevated
      germ cell markers in patients with carcinoma of unknown primary predict a
      response to cisplatin based chemotherapy.

PMID- 9038624
TI  - Comments on Prebiopsy neo-adjuvant endocrine therapy for breast cancer to prevent
      post-surgery trauma-induced growth factor and immune-suppression mediated tumour
      progression, Oliver et al., Eur J Cancer, 32A, No. 3, pp. 396-397, 1996.

PMID- 9038623
TI  - Polymorphisms in P21CIP1/WAF1 are not correlated with TP53 status in sporadic
      ovarian tumours.
AB  - In breast cancers and sarcomas, a variant polymorphism in the cell cycle
      inhibitor P21CIP1/WAF1 is under-represented in those individuals whose tumours
      contain mutated TP53. The aim of this study was to determine whether this variant
      polymorphism was also under-represented in those with ovarian carcinoma and TP53
      mutations. We studied lymphocyte DNA from 104 women with ovarian carcinoma, 15
      with borderline tumours and 16 with benign tumours, using a previously-reported
      PCR-RFLP technique. 96 of the ovarian carcinoma cases had been previously
      examined for mutations in TP53 and/or for overexpression of the TP53 protein. The
      variant allele was seen in 11 out of 104 women (10.6%) with ovarian carcinoma.
      There was no significant difference in the distribution of the variant allele in
      the women whose tumours had (7/47) or did not have (4/49) TP53 mutations (P =
      0.523). It does not appear that the presence of this variant allele of
      P21CIP1/WAF1 has any aetiological role in ovarian carcinomas. Studies in other
      tumours support this finding.

PMID- 9038625
TI  - A phase I/II trial of epirubicin and high dose tamoxifen as a potential modulator
      of multidrug resistance in advanced hepatocellular carcinoma.

PMID- 9038626
TI  - Serum and urinary vascular endothelial growth factor levels in non-small cell
      lung cancer patients.

PMID- 9038627
TI  - Abnormalities of the P16INK4A gene in thyroid cancer cell lines.

PMID- 9038628
TI  - Lack of carboplatin activity in malignant lymphomas.

PMID- 9038629
TI  - Radon exposure and incidence of paediatric malignancies.

PMID- 9038630
TI  - Very high male lung cancer incidence in areas with tobacco industries.

PMID- 9038631
TI  - Mixing anthracyclines and radiotherapy in early breast cancer: how safe is it?

PMID- 9038632
TI  - The clinical utility of viral load monitoring in HIV infection: strengths and
      limitations.

PMID- 9038633
TI  - Cervical cytology and colposcopy in clinics for sexually transmitted diseases-
      when are they appropriate?

PMID- 9038634
TI  - The role of vaccines in the control of STDs: HPV vaccines.
AB  - Prophylactic vaccines for genital human papillomavirus (HPV) infection have been
      shown to be feasible in animal models, and suitable vaccine material based on
      virus-like particles can be produced in bulk at reasonable cost. Initiation of
      phase III clinical trials will follow definition of trial outcome measures
      through further epidemiological studies, and development of assays of host
      protective immunity. Vaccines could in principle eliminate HPV-related disease,
      as the human race is the only natural host for the relevant papillomaviruses
      (PVs). Therapeutic vaccines for genital HPV infection are also possible, but have
      not yet been demonstrated as feasible in practice because the choice of vaccine
      antigens is difficult, the method of their optimal delivery is uncertain, and the
      nature of the relevant antiviral immunity is unknown. PV species specificity will
      require trials to be conducted in man, which will slow definition of an ideal
      vaccine.

PMID- 9038635
TI  - Systemic gonococcal infection.

PMID- 9038637
TI  - Uveitis associated with rifabutin and macrolide therapy for Mycobacterium avium
      intracellulare infection in AIDS patients.
AB  - OBJECTIVE: Uveitis has been increasingly recognised as a side effect of rifabutin
      regimens in the prophylaxis and treatment of Mycobacterium avium intracellulare
      (MAI) infection. This study describes the clinical features and analyses the
      factors associated with rifabutin induced uveitis. DESIGN: Retrospective
      observational study. SETTING: Tertiary care institution, The Royal Hospitals NHS
      Trust, London. PATIENTS: 68 HIV seropositive individuals receiving rifabutin for
      prophylaxis or treatment of MAI infection. RESULTS: 11 episodes of uveitis
      occurred in 10 different individuals at a median of 62 days. The disease was
      bilateral in four and unilateral in the remainder. All subjects experienced
      ocular pain and photophobia and 9 individuals had a significant reduction in
      visual acuity. Uveitis was treated with mydriatics and topical steroids and
      resolved in all cases when rifabutin was stopped. The risk of uveitis was
      significantly increased with concurrent clarithromycin therapy, Odds Ratio 13.08,
      95% Confidence Interval 1.98 to 83.12. CONCLUSION: Rifabutin can cause a
      reversible uveitis. This risk is increased with concurrent clarithromycin
      therapy. Adverse drug interactions can be an important cause of morbidity in
      patients with advanced HIV disease.

PMID- 9038638
TI  - Gonorrhoea in men: clinical and diagnostic aspects.
AB  - AIM: To review the features of gonococcal infection in men in the 1990s. METHODS:
      A retrospective study of all men with gonorrhoea presenting to an inner city
      department of genitourinary medicine in the years 1990 to 1992. RESULTS: 1749
      cases of gonorrhoea were seen in 1382 men. A high incidence of gonorrhoea was
      found in attenders of African or Caribbean extraction. In 228 men with a known
      date of infection, the incubation period, a mean of 8.3 days, was longer than
      previously described. The mean infectious period was 12.0 days. By 14 days 86.2%
      of men had developed symptoms. Of 1615 men with urethral infection 81.9%
      complained of discharge, while dysuria occurred in 52.8%. Discharge with dysuria
      were present in only 48.1% of patients. In 10.2% episodes of urethral infection
      the patients had no symptoms referable to their gonorrhoea. Urethral gonorrhoea
      was diagnosed by microscopy in 94.4% of symptomatic men and in only 81.1% of
      asymptomatic men. Microscopy of rectal samples were positive in 46.4% of cases.
      In this population, a dose of 2 g of ampicillin with 1 g of probenecid gave a
      high cure rate of gonorrhoea as long as infection was not due to penicillinase
      producing organisms. CONCLUSIONS: These data suggest that the incubation and
      infectious period of urethral gonorrhoea has increased compared with previous
      studies and that symptoms have altered. Only 48.1% of men described the classical
      symptoms of discharge with dysuria. Microscopy of urethral smears remains useful
      in symptomatic men but is less sensitive in those without symptoms.

PMID- 9038639
TI  - Painful swelling of the prepuce occurring during penile erection.

PMID- 9038636
TI  - Molecular immunopathogenesis of HIV infection.

PMID- 9038640
TI  - General practitioners' immediate management of men presenting with urethral
      symptoms.
AB  - OBJECTIVES: To describe the immediate reported management, by general
      practitioners (GPs), of men presenting with symptoms of urethral discharge, or
      dysuria only. SUBJECTS: All 692 GPs in practice in Brent, Harrow, Ealing,
      Hammersmith, and Hounslow (UK). METHOD: Data were collected using a GP completed
      questionnaire concerning the management of the last male patient seen, aged less
      than 40 years, complaining of urethral discharge, and the last male patient under
      40 years complaining of dysuria only. RESULTS: The response rate among GPs was
      52%. Fifty three per cent of men with urethral symptoms, 86% of men with a
      urethral discharge and 24% with dysuria only, were identified by GPs and referred
      without investigation or treatment to a genitourinary medicine clinic. Of men
      with dysuria only, 93% of investigations by GPs were reported to include a mid
      stream urine (MSU) specimen for bacteriology, and 19% a urethral swab for
      chlamydia. Seventy eight per cent of GPs reported using treatments with a broad
      spectrum antibiotic, 53% with trimethoprim, whilst 14% of GPs reported using a
      tetracycline in common use to treat non-gonococcal urethritis. Urine specimens
      were reported to be "culture positive" in 41% of men who had an MSU specimen
      tested, and 15% of men who had a urethral swab tested were reported to be
      chlamydia positive. CONCLUSION: The GPs included in this study were not a full
      sample, or representative of all the GPs, and the data are retrospective.
      Nevertheless, we found a large difference in GPs reported management for men with
      urethral symptoms according to whether or not urethral discharge was a reported
      complaint. Reported management is likely to be, at least, indicative of actual
      management. Therefore, the results suggest that assessment by GPs of men
      presenting with dysuria should be explored and more appropriate management
      strategies defined.

PMID- 9038641
TI  - Aspergillus infection of the epiglottis in a HIV positive patient.

PMID- 9038642
TI  - There is no longer a place for underage cytology in genitourinary medicine
      clinics.

PMID- 9038643
TI  - "Does ligase chain reaction assay of urine in the diagnosis of Chlamydia
      trachomatis offer significant improvement over existing diagnostic tests?"--a
      critical appraisal of the evidence.

PMID- 9038644
TI  - The Harrison Lecture. STD awareness today.

PMID- 9038645
TI  - Genitourinary medicine and the Internet No 3.

PMID- 9038646
TI  - Microsporidia: a new sexually transmissable cause of urethritis.

PMID- 9038647
TI  - Vertical transmission of human papillomavirus in cytologically normal women.

PMID- 9038648
TI  - Cytomegalovirus retinitis in a healthy antiretroviral naive HIV positive male
      with a CD4 count of 277/mm3.

PMID- 9038649
TI  - Acute cytomegalovirus prostatitis in AIDS.

PMID- 9038650
TI  - Systemic lupus erythematosus features in an AIDS patient: diagnostic problems in
      an African rural hospital.

PMID- 9038651
TI  - Rise in hepatitis A among gay men in the Thames regions 1995 and 1996.

PMID- 9038652
TI  - Services for female prostitutes in genitourinary medicine clinics in the UK.

PMID- 9038653
TI  - Self-reported discomfort associated with use of different nonoxynol-9
      spermicides.

PMID- 9038654
TI  - Crusted ("Norwegian") scabies in a specialist HIV unit.

PMID- 9038655
TI  - Balanitis and balanoposthitis: a review.

PMID- 9038656
TI  - Treating Helicobacter pylori--the best is yet to come?

PMID- 9038657
TI  - 1976 and all that!--20 years of antisecretory therapy.

PMID- 9038658
TI  - Increased production of interleukin 1 beta and hepatocyte growth factor may
      contribute to foveolar hyperplasia in enlarged fold gastritis.
AB  - BACKGROUND AND AIMS: It has been reported that eradication of Helicobacter pylori
      improves fold width in H pylori associated enlarged fold gastritis. The aim of
      this study was to clarify the mechanism of fold thickening in this condition.
      PATIENTS AND METHODS: In eight patients with enlarged fold gastritis and 13
      patients without enlarged folds, the presence of H pylori infection, inflammatory
      infiltrates, mucosal plasia, and epithelial cell proliferation in the body mucosa
      were investigated, and production of transforming growth factor alpha (TGF
      alpha), hepatocyte growth factor (HGF), and interleukin 1 beta (IL 1 beta) was
      determined by a competitive reverse transcription/polymerase chain reaction
      method and in vitro short-term culture of biopsy specimens. RESULTS: In the
      patients with enlarged fold gastritis, inflammatory infiltrates including
      macrophages increased with H pylori colonisation in the body. Foveolar thickness
      and proliferating cell nuclear antigen (PCNA) labelling index were increased.
      Messenger RNA levels of HGF, but not TGF alpha, were increased, and release of
      HGF and IL 1 beta was increased. HGF release, which was positively correlated
      with IL 1 beta release and foveolar thickness, decreased in the presence of IL 1
      receptor antagonist. After eradication of H pylori, inflammatory infiltrates, IL
      1 beta and HGF release decreased with concomitant decreases in PCNA labelling
      index, foveolar thickness and fold width. CONCLUSIONS: Increased IL 1 beta and
      HGF production caused by H pylori infection may contribute to fold thickening of
      the stomach by stimulating epithelial cell proliferation and foveolar hyperplasia
      in patients with enlarged fold gastritis.

PMID- 9038659
TI  - Effects of Helicobacter pylori vacuolating cytotoxin on primary cultures of human
      gastric epithelial cells.
AB  - BACKGROUND: Many Helicobacter pylori strains produce a cytotoxin that induces
      cytoplasmic vacuolation in various types of eukaryotic cells. In contrast with
      the marked cell vacuolation that occurs in vitro in response to this cytotoxin,
      comparatively little epithelial vacuolation has been observed in the gastric
      mucosa of H pylori infected persons. AIMS: Experiments were performed to
      determine the susceptibility of human gastric epithelial cells in vitro to H
      pylori vacuolating cytotoxin activity. METHODS: Human gastric epithelial cells,
      harvested from upper gastrointestinal endoscopic biopsy specimens, were incubated
      overnight with broth culture supernatants from either a wild type cytotoxin
      producing (tox+) H pylori strain or an isogenic mutant strain that lacks
      cytotoxin activity. RESULTS: Prominent cytoplasmic vacuolation occurred in
      response to tox+ supernatant, but not supernatant from the isogenic mutant
      strain. Primary human gastric epithelial cells were significantly more sensitive
      to H pylori vacuolating cytotoxin activity than were either HeLa or AGS cells.
      Exposure of human gastric epithelial cells to high concentrations of tox+
      supernatant for 48 hours caused lethal cell injury. CONCLUSIONS: These studies
      indicate that primary human gastric epithelial cells are highly sensitive to H
      pylori vacuolating cytotoxin activity.

PMID- 9038661
TI  - Ornithine decarboxylase activity is a marker of premalignancy in longstanding
      Helicobacter pylori infection.
AB  - BACKGROUND: Longstanding Helicobacter pylori infection may increase the risk of
      developing gastric adenocarcinoma. The sequence of chronic active gastritis
      leading to gastritis with atrophy and subsequent intestinal metaplasia is thought
      to be a key step in gastric carcinogenesis. Ornithine decarboxylase (ODC)
      activity is increased in some pre-malignant gastrointestinal conditions and is
      essential for malignant transformation in vitro. AIMS: To measure ODC activity in
      the antrum of H pylori infected and non-infected subjects and to relate this to
      histological abnormalities associated with recent and longstanding H pylori
      infection. METHODS: Six antral mucosal biopsy specimens were obtained from 75
      patients for detailed histological assessment and measurement of ODC activity.
      Samples were measured in duplicate and results expressed as median, interquartile
      range in pmol/mg protein/h. RESULTS: ODC activity was significantly higher in H
      pylori positive (164, 88-259 pmol/mg/h) than H pylori negative subjects (99.8, 55
      158 pmol/mg/h, p = 0.003). However the presence of gastritis, irrespective of the
      severity of inflammation or activity had no influence on ODC activity. Gastritis
      with atrophy was associated with increased ODC activity, which was closely
      related to the severity of the atrophy (p = 0.01). Similarly, ODC activity was
      significantly increased in subjects with intestinal metaplasia (196, 83-25)
      compared with those without intestinal metaplasia (111.7, 65-175, p < 0.04).
      CONCLUSIONS: These results indicate that the histological changes associated with
      longstanding H pylori infection rather than inflammation alone are associated
      with increased polyamine biosynthetic activity. This may be relevant to H pylori
      associated gastric carcinogenesis.

PMID- 9038660
TI  - Profile of Helicobacter pylori cytotoxin derived from two areas of Japan with
      different prevalence of atrophic gastritis.
AB  - BACKGROUND AND AIM: To clarify the roles of Helicobacter pylori cytotoxin in
      gastric atrophy, the cytotoxin positive rate and cytotoxin activity in Fukui and
      Okinawa, where the prevalence of atrophic gastritis and gastric cancer risk are
      quite different, were studied. MATERIALS: Seventy three strains from Fukui and 51
      from Okinawa were examined. METHODS: The validation of atrophy was done by
      endoscopy, being confirmed with histology. The supernatant of liquid H pylori
      culture media was concentrated 20-fold, serially diluted, using doubling
      dilutions, and scored from 1 to 8. The semi-quantitated cytotoxin activity was
      expressed as the maximum dilution score yielding > 50% A431 cell vacuolation,
      being standardised with bacterial density. RESULTS: The cytotoxin activity of the
      strains from Fukui was highly diverse compared with that from Okinawa, although
      the cytotoxin positive rate was not different. In Fukui strains, the grade of
      atrophy and the cytotoxin activity were correlated (p < 0.05). In addition, the
      cytotoxin activity of the strains from all patients in Okinawa, most of whom
      showed closed-type/mild atrophy, was significantly lower than that of the strains
      from the patients with open-type/severe atrophy in Fukui (6.46 (5.53) v 9.76
      (8.80), p < 0.05), (mean (SEM)). CONCLUSION: The difference in profile of the
      cytotoxin activity in the two areas was related to the difference in the
      prevalence of atrophic gastritis.

PMID- 9038662
TI  - Increased small intestinal apoptosis in coeliac disease.
AB  - BACKGROUND: Coeliac disease (CD) mucosa is flattened despite epithelial
      hyperproliferation. AIMS: To establish mechanisms of cell loss in CD. PATIENTS:
      14 controls, 17 active CD patients, and 16 maintained with gluten free diet.
      METHODS: Programmed cell death was examined in small intestinal biopsy specimens
      by staining fragmented DNA using terminal uridine deoxynucleotidyl nick end
      labelling (TUNEL), in comparison with haematoxylin and eosin stained adjacent
      sections. Double staining with anti-CD45 antibodies determined the origin of
      apoptotic cells. Apoptosis was graded from 1-3 (< 5, 5-20, > 20% respectively).
      Proliferating cells, immunostained by Ki-67 (MIB-1) antibody, were counted.
      RESULTS: Apoptotic cells were seen rarely by haematoxylin and eosin but more
      readily by TUNEL. In controls, 1.4 +/- 0.2% of epithelial cells were apoptotic
      (mean grade 1.1), mainly located in the upper villus. In active CD, frequent
      apoptotic cells were distributed throughout the crypt-villus unit (mean grade
      2.4), decreasing after treatment to 1.1 (p < 0.001) even when still
      histologically abnormal. CD45 antibodies rarely stained apoptotic cells in active
      CD. The number of TUNEL positive cells correlated with proliferating cell number
      (p < 0.001). CONCLUSION: Enterocyte apoptosis is greatly increased in untreated
      CD, correlates with proliferation, and falls to normal with a gluten free diet,
      before histological improvement. Increased apoptosis may be responsible for
      villous atrophy in CD.

PMID- 9038663
TI  - Analysis of interleukin-4 and interleukin-10 and their association with the
      lymphocytic infiltrate in the small intestine of patients with coeliac disease.
AB  - BACKGROUND: Concentrations of pro-inflammatory cytokines are raised in the small
      intestine of patients with coeliac disease after ingestion of gluten but there
      are equivalent data on interleukin-4 (IL-4) and interleukin-10 (IL-10) producing
      cells. These cytokines are known to exert important regulatory effects on pro
      inflammatory cytokine production from lymphocytes and macrophages. AIMS: To
      investigate whether there is a primary deficiency of IL-4 and IL-10 producing
      cells and their site of production in the small intestine of patients with
      coeliac disease in relation to the changes in inflammatory cell infiltrate.
      PATIENTS: Jejunal biopsy specimens from patients with coeliac disease (11
      untreated, 10 treated) and nine disease controls were studied. METHODS:
      Immunohistochemical staining of sections for IL-4 and IL-10 cytokines and the
      cell phenotypic markers CD3 (T lymphocytes) and CD45 (total inflammatory cell
      infiltrate) was carried out using monoclonal antibodies. Expression of IL-4 and
      IL-10 messenger RNA was detected by in situ hybridisation with oligonucleotide
      probe cocktails for each cytokine. RESULTS: IL-4 and IL-10 mRNA and protein were
      detected in the lamina propria of treated and untreated coeliac patients and
      disease controls but not in the epithelium. A significant increase in the number
      of CD45 (p < 0.005) and CD3 (p < 0.05) positive cells was found in the lamina
      propria of patients with untreated coeliac disease compared with treated coeliac
      patients and disease controls but there were no differences in IL-4 or IL-10
      between these groups with either method. CONCLUSIONS: There is no primary
      deficiency of IL-4 and IL-10 producing cells in the small intestine of patients
      with coeliac disease. Detectable concentrations of IL-4 and IL-10 were found in
      control patients which suggests that these cytokines are involved in normal
      mucosal immunoregulation. The increased number of T lymphocytes but not IL-4 or
      IL-10 producing cells in the lamina propria of patients with untreated than in
      those with treated disease suggests not only that the lamina propria is the major
      mucosal compartment for cytokine production but that newly recruited mucosal T
      lymphocytes are directed to a predominant Th1 and not a Th2 cytokine response in
      coeliac patients on a diet containing gluten.

PMID- 9038664
TI  - Investigation of chronic diarrhoea in acquired immunodeficiency syndrome. A
      prospective study of 155 patients.
AB  - BACKGROUND AND AIMS: The optimum diagnostic investigation for patients with
      acquired immunodeficiency syndrome (AIDS) and diarrhoea is not known. Often no
      pathogen is detected and it is unclear whether this is because pathogens are
      absent in some patients or the investigations used fail to detect them. The
      hypothesis that AIDS related diarrhoea is usually due to an infection, which can
      be identified by a simple diagnostic strategy based on the results of intensive
      investigation of a cohort of such patients, was investigated. METHODS: 155
      patients with AIDS and chronic diarrhoea underwent contemporaneous examination of
      stools, duodenal, jejunal, and rectal biopsy specimens and duodenal aspirate for
      bacterial, protozoal, and viral pathogens. A decision tree analysis was used to
      determine the best sequential diagnostic strategy for clinicians. RESULTS: 128 of
      155 patients investigated (83%) had at least one potential pathogen. The
      presenting clinical features could not predict the presence or site of the
      pathogens. Stool analysis identified the most pathogens (93 of 199, 47%). Rectal
      biopsy was essential for the diagnosis of cytomegalovirus and adenovirus.
      Duodenal biopsy was as helpful as jejunal biopsy and detected some treatable
      pathogens missed by other methods. Electron microscopy, impression smears, and
      duodenal aspirate yielded little extra information. If gut biopsy was reserved
      for patients without a stool pathogen, some treatable pathogens would have been
      missed. CONCLUSION: Most patients with AIDS and chronic diarrhoea have at least
      one gut pathogen, which can be identified by stool analysis and light microscopic
      examination of duodenal and rectal biopsies. Some pathogens will be missed unless
      all these investigations are done on all such patients.

PMID- 9038665
TI  - Influence of postoperative enteral nutrition on postsurgical infections.
AB  - BACKGROUND: This study was undertaken to test the hypothesis that early enteral
      nutrition might reduce the incidence of serious complications after major
      abdominal surgery. METHODS: In a randomised double blind prospective trial 30
      patients received Nutri-drink and 30 patients received placebo through a
      nasoduodenal feeding tube. On the day of operation the patients were given median
      600 ml of either nutrition or placebo, 60 ml per hour. On the first postoperative
      day the patients received either 1000 ml (median) of nutrition or placebo, on day
      2 1200 ml (median) nutrition, 1400 ml placebo, on day 3 1000 ml (median)
      nutrition, 1150 ml placebo, and on day 4 1000 ml (median) nutrition, 800 ml
      placebo. All patients were followed up for 30 days by the same investigator.
      RESULTS: The two groups were similar with regard to nutritional status and type
      of operation. The rate of postoperative infectious complications was
      significantly lower in the nutrition group, two of 30 compared with 14 of 30 in
      the placebo group (p = 0.0009). CONCLUSION: Early enteral nutrition given to
      patients after major abdominal surgery results in an important reduction in
      infectious complications.

PMID- 9038667
TI  - Collagenous colitis: a retrospective study of clinical presentation and treatment
      in 163 patients.
AB  - BACKGROUND: Data on collagenous colitis have been based on a limited number of
      patients. AIMS: To obtain more information on this disease from a register set up
      at Orebro Medical Center Hospital. PATIENTS AND METHODS: Twenty five Swedish
      hospitals have contributed to this patient register, which comprises 163
      histopathologically verified cases. Clinical data were retrospectively analysed.
      RESULTS: Collagenous colitis followed a chronic intermittent course in most cases
      (85%) with a sudden onset in 42%. Symptoms were chronic watery diarrhoea, often
      nocturnal (27%), abdominal pain (41%), and weight loss (42%). Sixty six patients
      (40%) had one or more associated diseases. Routine laboratory data were mostly
      normal. The median age at diagnosis was 55 (range 16-86) years, but 25% of the
      patients were younger than 45 years. Seven patients died of unrelated diseases.
      The response rate for sulphasalazine was 59%, and 50% and 40% for mesalazine and
      olsalazine. Prednisolone was most effective with a response rate of 82%, but the
      required dose was often high and the effect was not sustained after withdrawal.
      Antibiotics were efficient in 63%. Cholestyramine and loperamide had response
      rates of 59% and 71% respectively. CONCLUSIONS: Collagenous colitis follows a
      chronic continuous course. Symptoms can be socially disabling, but the disease
      does not seem to have a malignant potential. A plan for the treatment of a newly
      diagnosed patient with collagenous colitis is proposed.

PMID- 9038666
TI  - Interleukin 10 suppresses experimental chronic, granulomatous inflammation
      induced by bacterial cell wall polymers.
AB  - BACKGROUND AND AIMS: Interleukin 10 (IL10) inhibits monocyte/macrophage and T
      lymphocyte effector functions. This study examined the effect of systemically
      administered IL10 on acute and chronic granulomatous enterocolitis, hepatitis,
      and arthritis in a rat model. METHODS: Lewis rats were injected intramurally with
      streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Beginning 12 hours
      before PG-APS injection, rats were treated daily with subcutaneous murine
      recombinant IL10 or vehicle for three or 17 days. RESULTS: IL10 attenuated acute
      enterocolitis in a dose dependent fashion (p < 0.01). Protective effects were
      more profound in the chronic granulomatous phase with decreased enterocolitis and
      markedly inhibited leucocytosis, hepatic granulomas, and chronic erosive
      arthritis (p < 0.001). IL10 downregulated tissue IL1, IL6, tumour necrosis factor
      alpha, and interferon gamma gene expression, consistent with the in vitro effects
      of IL10 on PG-APS-stimulated splenocytes. Caecal IL1 protein concentrations and
      IL2 and interferon gamma secretion by in vitro stimulated mesenteric lymph nodes
      were downregulated in IL10 treated animals. CONCLUSIONS: These results indicate
      that exogenous IL10 can inhibit experimental granulomatous inflammatory responses
      and suggest that IL10 treatment could be an effective new therapeutic approach in
      human disorders such as Crohn's disease, rheumatoid arthritis, and sarcoidosis.

PMID- 9038669
TI  - Longterm effects of endoscopic sphincterotomy on gall bladder motility.
AB  - BACKGROUND: Some of patients with an intact gall bladder develop acute
      cholecystitis or have gall bladder stone formation after endoscopic
      sphincterotomy. Endoscopic sphincterotomy may affect gall bladder motility. AIMS:
      To prospectively evaluate longterm effect of endoscopic sphincterotomy on gall
      bladder motility. PATIENTS: Thirty two patients with an intact gall bladder (15
      with and 17 without gall bladder stones) who underwent endoscopic sphincterotomy
      for choledocholithiasis. METHODS: Gall bladder function was examined before and
      at from seven days to five years after sphincterotomy. Gall bladder volume, at
      fasting and after caerulein administration, was determined by ultrasonography.
      RESULTS: After endoscopic sphincterotomy, the enlarged orifice remained patent
      during a five year follow up period. One patient with gall bladder stones
      subsequently developed acute cholecystitis, the remaining being asymptomatic. In
      the patients before sphincterotomy, particularly in those with gall bladder
      stones, the gall bladder showed larger fasting volume and lower caerulein
      stimulated maximum contraction than normal controls. Throughout five years after
      sphincterotomy, fasting volume of the gall bladder decreased and its maximum
      contraction increased, regardless of gall bladder stones; significantly different
      from the values before sphincterotomy (p < 0.05). CONCLUSIONS: Endoscopic
      sphincterotomy decreases fasting volume of the gall bladder and increases its
      contraction ability for a long period. These changes may rather decrease the risk
      of future acute cholecystitis or gall stone formation.

PMID- 9038668
TI  - A retrospective comparison of endoscopic stenting alone with stenting and
      radiotherapy in non-resectable cholangiocarcinoma.
AB  - BACKGROUND AND AIMS: Radiotherapy has been reported to be of benefit in
      prolonging the survival of patients with cholangiocarcinoma. This study examined
      whether radiotherapy in addition to endoscopic stenting improved survival.
      SUBJECTS: 56 patients with obstructive jaundice due to histologically confirmed
      non-resectable cholangiocarcinoma. METHODS: A retrospective analysis of these
      patients who were treated either with endoscopic biliary stenting followed by
      external beam radiotherapy and internal iridium-192 brachytherapy (n = 28) or
      with stenting alone (control group; n = 28). RESULTS: The two groups were well
      matched in age, sex, and stricture type. Eighteen patients had a type I stricture
      (control group: 11; radiotherapy group: 7) at the time of diagnosis and 38 had a
      type II or III stricture (control group: 17; radiotherapy group: 21). The median
      (range) overall survival from diagnosis was seven (1-29) and 10 (4-75) months in
      the control and radiotherapy groups respectively: This difference did not reach
      statistical significance (p = 0.06), but survival plots indicated a survival
      advantage in the radiotherapy group in the first nine months after diagnosis.
      Approximately one third survived longer than one year in both groups. More
      patients in the radiotherapy group required a stent change (1.9 v 0.9: p = 0.05),
      and also had a longer overall inpatient stay (42 days v 19: p < 0.001). When
      examined on the basis of stricture type, there was a survival advantage in the
      first 10 months after diagnosis in those with a type II/III stricture (seven and
      11 months in the radiotherapy and control groups respectively: 0.01 < p < 0.05).
      There was no difference in survival between the groups in those with a type I
      stricture. Numbers surviving longer than one year, stent survival, and number of
      stent changes were all similar between the two groups when examined on the basis
      of stricture type, but length of hospital stay remained considerably longer in
      all patients receiving radiotherapy. CONCLUSION: The survival advantage of
      radiotherapy in those with a type II/III stricture is seen only in the first 10
      months after diagnosis. The costs of radiotherapy and significantly increased
      time spent in hospital, however, raise doubts over its routine use in the
      management of non-resectable cholangiocarcinoma.

PMID- 9038670
TI  - Natural history of polypoid lesions in the gall bladder.
AB  - BACKGROUND: Although polypoid lesions of the gall bladder are frequently observed
      in asymptomatic subjects, the natural history of these lesions has never been
      studied using ultrasonography. AIM: The natural history of polypoid lesions of
      the gall bladder was investigated using ultrasonography. SUBJECTS: Among 4343
      patients who presented to the outpatient clinic of Tsuchiura Kyodo General
      Hospital in 1988, 111 subjects were diagnosed as having polypoid lesions of the
      gall bladder by ultrasonography. Among these patients, two had gall bladder
      carcinoma. The remaining 109 subjects (58 female; age: median 54, range 25-89)
      were enrolled in this study. METHODS: The subjects were followed up by
      ultrasonography once or twice a year until 1994. RESULTS: Four patients received
      cholecystectomy and two patients died of other causes during the observation
      period. In one patient, gall bladder carcinoma was found, but its location was
      different from that of the pre-existing polyp. The size of the lesions did not
      change in 88.3% of the other 130 patients during this period, even among those in
      whom the initial size of the lesion exceeded 10 mm. There was no apparent
      correlation between the change in the diameter of the polypoid lesions and
      patients' sex or age. CONCLUSION: Most polypoid lesions of the gall bladder
      detected by ultrasonography are benign.

PMID- 9038671
TI  - Incidence of persistent symptoms after laparoscopic cholecystectomy: a
      prospective study.
AB  - BACKGROUND AND AIMS: Laparoscopic cholecystectomy is the standard treatment for
      symptomatic gall stone disease. This study aimed to assess the effect of the
      operation on patients' symptoms. METHODS: One hundred consecutive patients
      undergoing laparoscopic cholecystectomy between June 1994 and June 1995 were
      evaluated using standard questionnaires examining demographic details, indication
      for laparoscopic cholecystectomy, characteristics of pain, and other associated
      dyspeptic and colonic symptoms. A history of psychiatric disturbances and of
      hysterectomy were also recorded. The same questionnaires were administered again
      six months after the operation. Operation notes and histological reports were
      reviewed. RESULTS: Three patients were converted to open surgery and were
      excluded from analysis. The median age of the remaining 97 patients was 50.9 (19
      85) years; 19 were men. There was one complication each of bleeding and biliary
      leak. Indications for laparoscopic cholecystectomy were biliary type pain (66
      patients) and complicated gall stone disease (acute cholecystitis 21, cholestatic
      jaundice six, and pancreatitis four). Thirteen patients (13%) had persistent pain
      and two (3%) developed diarrhoea at follow up. Only one patient with persistent
      pain after laparoscopic cholecystectomy originated from the complicated gall
      stone disease group. Logistic discriminant analysis showed that bloating (p <
      0.001), constipation (p < 0.05), and previous and current use of psychotrophic
      drugs (p < 0.001) were significantly more common among those with a poor outcome
      after laparoscopic cholecystectomy. Heartburn was unaffected. Of patients with
      persistent symptoms after cholecystectomy 77% had no or mild histological changes
      of cholecystitis as compared with 30% in the pain free group. CONCLUSIONS: The
      incidence of persistent pain after laparoscopic cholecystectomy was 13%.
      Abdominal bloating and psychiatric medications were predictive for persistence of
      pain after laparoscopic cholecystectomy.

PMID- 9038672
TI  - Hepatoblastoma and APC gene mutation in familial adenomatous polyposis.
AB  - BACKGROUND: Hepatoblastoma is a rare, rapidly progressive, usually fatal
      childhood malignancy, which if confined to the liver can be cured by radical
      surgical resection. An association between hepatoblastoma and familial
      adenomatous polyposis (FAP), which is due to germline mutation of the APC
      (adenomatous polyposis coli) gene, has been confirmed, but correlation with site
      of APC mutation has not been studied. AIM: To analyse the APC mutational spectrum
      in FAP families with hepatoblastoma as a possible basis to select kindreds for
      surveillance. PATIENTS: Eight patients with hepatoblastoma in seven FAP kindreds
      were compared with 97 families with identified APC gene mutation in a large
      Registry. METHODS: APC gene mutation was evaluated by RNase protection assay or
      in vitro synthesis protein assay. The chi 2 test and correlation were used for
      data analysis. RESULTS: APC gene mutation was identified in all seven FAP
      kindreds in which an at risk member developed hepatoblastoma. A male predominance
      was noted (six of eight), similar to literature cases (18 of 25, p < 0.01.
      Mutations were restricted to codons 141 to 1230, but no significant difference in
      site of mutation between pedigrees with and without hepatoblastoma was
      identified. CONCLUSIONS: Hepatoblastoma occurs primarily in boys in FAP kindreds
      and is associated with germline APC mutation in the 5' end of the gene. However,
      the site of APC mutation cannot be used to predict occurrence of this
      extracolonic cancer in FAP pedigrees.

PMID- 9038673
TI  - Liver transplantation for haemophiliacs with hepatitis C cirrhosis.
AB  - BACKGROUND: Experience of liver transplantation in haemophiliacs with end stage
      hepatitis C liver disease is limited and particularly difficult questions are
      raised when there is also HIV infection. AIMS: This is the first report in Great
      Britain to describe the operative replacement therapy and initial outcome in four
      haemophiliacs with end stage HCV cirrhosis. PATIENTS: Two patients had factor
      VIII, one had factor IX, and one had factor X deficiency. One patient had also
      contracted HIV infection from factor replacement but had no AIDS defining
      illnesses. METHODS: Intraoperatively patients were given either factor VIII
      infusions, factor IX bolus, or fresh frozen plasma, according to formulae devised
      to calculate exact clotting factor requirements. Baseline preoperative
      coagulation studies included prothrombin time, activated partial thromboplastin
      time, fibrinogen concentrations, and factor VIII, IX, and X concentrations.
      Factor concentrations were then assayed at 12, 24, 48, and 72 hours
      postoperatively. RESULTS: Postoperatively all patients had coagulation factor
      concentrations sustained within the normal ranges by 72 hours unsupported (137,
      125, 95, 104 IU/dl), representing de novo synthesis by the graft. Transfusion
      requirements during the operative and immediate post-transplant period were no
      greater than those of patients without clotting disorders. Two patients had
      episodes of bleeding postoperatively, one of which was fatal, occurring at the
      site of a previous untreated subdural bleed. In both instances the bleeding
      occurred in the presence of normal concentrations of clotting factor. The
      remaining three patients are at 6, 6, and 12 months post-transplant and
      remarkably improved clinically with sustained factor concentrations. One patient
      has evidence of graft dysfunction from HCV recurrence and all have evidence of
      recurrent viraemia with HCV on polymerase chain reaction studies. CONCLUSIONS:
      Orthotopic liver transplantation should be considered in haemophiliac patients
      with end stage liver disease from hepatitis C infection with or without
      concomitant HIV infection. Their clinical condition is likely to be greatly
      improved by orthotopic liver transplantation and the haemophilia cured with only
      a small risk of severe graft dysfunction from recurrent HCV infection.

PMID- 9038674
TI  - Quantification of serum hepatitis C virus core protein level in patients
      chronically infected with different hepatitis C virus genotypes.
AB  - BACKGROUND/AIM: A novel fluorescent enzyme immunoassay (FEIA) for the detection
      and quantification of serum hepatitis C virus (HCV) core protein was developed.
      The aim of this study was to evaluate the relation among serum HCV core protein
      level, HCV RNA level, and HCV genotype in patients with chronic HCV infection.
      PATIENTS AND METHODS: Serum HCV core protein, HCV RNA, HCV genotype were
      determined in 175 patients using the FEIA, branched DNA assay (Quantiplex HCV RNA
      ver 1.0), and serologically defined genotyping assay, respectively. For the
      specificity, all 13 patients seronegative for anti-HCV were negative for serum
      core antigen and HCV RNA by FEIA and bDNA, respectively. RESULTS: FEIA assay
      seems to be more sensitive than bDNA for patients with HCV type 2 infection
      (detection: 83.4% v 63.4%, p < 0.01). There was a good overall correlation
      between the FEIA and bDNA results. However, when the patients were stratified
      into their HCV types, a correlation was observed in HCV type 1 but not in type 2
      infection. Patients with HCV type 2 infection had a lower serum HCV core protein
      level (median 56 RFI) compared with type 1 infection (median 149 RFI, p < 0.01).
      Thirty seven patients subsequently received interferon alpha therapy, patients
      who showed a complete and sustained response had a lower pretreatment serum HCV
      core protein level compared with patients who had a relapse and nonresponders (36
      v 338 RFI, p < 0.01). CONCLUSIONS: This study showed that FEIA (1) is a good
      assay for the detection and quantification of serum HCV core protein level, (2)
      is also very sensitive in detecting HCV core protein in patients with HCV type 2
      infection, and (3) may have a role as a predictor of subsequent response to
      interferon therapy.

PMID- 9038675
TI  - Cytokines and Helicobacter pylori--a growth area.

PMID- 9038676
TI  - Cell death--where is thy sting?

PMID- 9038677
TI  - Sphincterotomy and the gall bladder--a slice of luck.

PMID- 9038678
TI  - Hope for haemophilic patients with hepatitis.

PMID- 9038679
TI  - Reflux oesophagitis and acid exposure.

PMID- 9038680
TI  - Microvascular disease in the human large bowel.

PMID- 9038681
TI  - The potential for growth hormone in the management of heart failure.

PMID- 9038682
TI  - Atrial fibrillation and the pituitary-thyroid axis: a re-evaluation.

PMID- 9038683
TI  - Is long QT syndrome entering the era of molecular diagnosis?

PMID- 9038685
TI  - Putting the heart back into audit.

PMID- 9038684
TI  - The relation between Chlamydia pneumoniae and atherosclerosis.

PMID- 9038686
TI  - Sir William Osler (1849-1919).

PMID- 9038687
TI  - Ticlopidine and aspirin interactions.
AB  - The risk-benefit balance when aspirin is compared with aspirin combined with
      ticlopidine is being investigated in several multicentre trials (MUSIC and WEST
      II versus TASTE, MUST, and STARS respectively). Cardiologists follow one of two
      strategies. Some prefer a more aggressive antiplatelet regimen, disregarding the
      risk of neutropenia (0.7%) because they want to avoid lessening the therapeutic
      effect of vessel patency obtained with stent implantation. Others give only
      aspirin (a money saving approach) confident that IVUS inspection (an expensive
      approach) will allow an adequate evaluation of full stent expansion and lesion
      coverage, despite a more pronounced activation of the coagulation cascade. Our
      impression so far is that the combination of ticlopidine and aspirin has a more
      favourable risk-effect balance.

PMID- 9038688
TI  - Antithrombotic treatment in stable coronary syndromes: long-term intermittent
      urokinase therapy in end-stage coronary artery disease and refractory angina
      pectoris.
AB  - Interventions that modify lipid metabolism and blood coagulation have been shown
      to favourably influence the natural course of coronary artery disease in terms of
      the primary prevention and treatment of acute cardiovascular events. Various
      findings suggest that such interventions may also preserve and enhance myocardial
      perfusion in the chronic stage of the disease. Long-term intermittent urokinase
      therapy was developed for patients with end-stage coronary artery disease and
      refractory angina pectoris. A dose of 500,000 IU of urokinase given intravenously
      as a bolus three times a week for of 12 weeks reduced symptoms by 70% and was
      accompanied by objective improvements in myocardial perfusion and an increase of
      ergometric exercise capacity. The possible therapeutic mechanisms of long-term
      intermittent urokinase therapy-improvement of rheological blood properties
      mediated by fibrinogen reduction, thrombolysis of non-occlusive subclinical
      thrombi, and regression of atherosclerotic plaques-are discussed in the context
      of other antithrombotic approaches.

PMID- 9038689
TI  - Flow resistance of individual neutrophils in coronary artery disease: decreased
      pore transit times in acute myocardial infarction.
AB  - OBJECTIVE: To investigate single neutrophil flow resistance in coronary artery
      disease, including myocardial infarction before initiation of reperfusion
      therapy. DESIGN: Neutrophil flow resistance was measured in 93 subjects in five
      groups: (group 1) 28 patients within 12 hours after the onset of myocardial
      infarction, before reperfusion therapy; (group 2) 18 with unstable angina; (group
      3) 13 with stable angina; (group 4) 13 age matched patients without coronary
      disease, and (group 5) 21 healthy volunteers. MAIN PARAMETERS: Single neutrophil
      transit times through 8 microns oligopore filters determined with a modified cell
      transit analyser. RESULTS: Leucocyte count (10(9)/l) was increased in coronary
      disease, especially in myocardial infarction and unstable angina (mean and 95%
      confidence intervals for groups 1 to 5: 12.6 (11.0 to 14.2), 11.3 (8.5 to 14.1),
      8.5 (7.4 to 9.6), 8.0 (6.0 to 10.0), 7.0 (6.1 to 7.9)). Polymorphonuclear
      granulocyte (PMN) flow resistance correlated negatively with white blood cell
      (WBC) count and was significantly decreased in coronary artery disease (CAD),
      especially in myocardial infarction; mean transit times (ms) for groups 1 to 5
      were: 13.6 (11.8 to 15.4), 16.9 (13.9 to 19.0), 16.9 (12.8 to 21.0), 22.0 (19.6
      to 24.4), and 18.6 (15.7 to 21.5). CONCLUSION: Neutrophil flow resistance was
      decreased in CAD, especially in myocardial infarction before reperfusion therapy.
      In contrast to previous findings in reperfused myocardial infarction, the present
      study showed that stiffened PMNs were not yet present in the circulating blood
      pool. Thus a pharmacological approach aimed at suppressing leucocyte activation
      before or during reperfusion therapy may be feasible.

PMID- 9038692
TI  - Visualisation of exercise-induced ischaemia of the right ventricle by thallium
      201 single photon emission computed tomography.
AB  - OBJECTIVE: Exercise thallium-201 (201T1) single photon emission computed
      tomography (SPECT) has been used to detect potential ischaemia in the left
      ventricular myocardium but not in the right ventricle. The purpose of this study
      was to establish the clinical usefulness of a right ventricular polar map of
      201T1 SPECT for visualisation of exercise-induced right ventricular ischaemia.
      METHODS: Myocardial 201T1 SPECT was obtained immediately after treadmill exercise
      in 97 patients with suspected coronary artery disease. A region of interest was
      placed over the right ventricle (RV) on post-stress transaxial images. Short axis
      images of this region were generated and reconstructed as a bull's eye polar map.
      Normal ranges of RV 201T1 uptake were determined in 12 patients with normal
      coronary arteries. Scintigraphic criteria for identifying RV perfusion
      abnormality were derived from 25 patients with right coronary artery (RCA)
      stenosis greater than 75%. These criteria were applied to 60 consecutive patients
      with suspected coronary artery disease. RESULTS: Perfusion defects in the RV were
      larger in patients with proximal RCA stenosis than in those with distal RCA
      stenosis (mean (SD) 28 (16)% v 6 (5)%, P < 0.001). The sensitivity and
      specificity of the RV polar map for the detection of proximal RCA stenosis were
      67% (8/12) and 98% (47/48), respectively. RV perfusion defects became
      undetectable in 9 patients who had successful percutaneous transluminal coronary
      angioplasty to a proximal RCA lesion. CONCLUSIONS: A right ventricular polar map
      display was useful for visualising exercise-induced right ventricular ischaemia.

PMID- 9038691
TI  - Impaired left ventricular filling dynamics in patients with angina and
      angiographically normal coronary arteries: effect of beta adrenergic blockade.
AB  - OBJECTIVE: To assess exercise performance and resting left ventricular filling
      dynamics in patients with syndrome X (SX) in basal conditions and after 10 days
      treatment with oral atenolol. DESIGN AND PATIENTS: Exercise performance was
      studied and left ventricular filling assessed by Doppler-derived transmitral flow
      pattern analysis in 22 patients (16 female, mean (SD) age 53 (4) years) with
      angina, a positive exercise test, and angiographically smooth coronary arteries.
      Patients were studied after two 10 day treatment periods with either atenolol or
      placebo in a single-blind, randomised, crossover trial. The same protocol was
      followed in 10 patients with documented coronary artery disease (CAD) and in 13
      controls (C). RESULTS: Unlike the controls, patients with SX and those with CAD
      consistently showed exercise-induced ST segment abnormalities and impaired
      resting left ventricular filling while on placebo. Atenolol significantly reduced
      episodes of angina, completely prevented exercise-induced ST segment changes in
      18 SX patients, and delayed their onset in all patients with CAD: in both groups
      the agent significantly improved Doppler-derived indices (mean (SD)) of
      ventricular filling (E/A 0.97 (0.27) v 1.22 (0.32) and 0.84 (0.21) v 1.19 (0.37),
      respectively). CONCLUSIONS: The objective documentation of left ventricular
      filling abnormalities may be useful in confirming the clinical diagnosis of SX
      and in providing objective evidence of therapeutic benefit. The similarity of the
      symptoms and electrocardiographic and ventricular filling abnormalities found in
      patients with SX and in those with CAD suggests that ischaemia is involved in
      both groups.

PMID- 9038690
TI  - Associations between circulating components of the renin-angiotensin-aldosterone
      system and left ventricular mass.
AB  - OBJECTIVE: Cardiac growth may be modulated in part by the trophic effects of
      neurohormones. The aim of the present study was to investigate the relation
      between the basal activity of the renin-angiotensin-aldosterone system and left
      ventricular mass. DESIGN: A population based sample of 615 middle-age subjects
      was studied by standardised echocardiography; anthropometric measurements; and
      biochemical quantification of renin, pro-renin, angiotensinogen, angiotensin
      converting enzyme (ACE), and aldosterone. RESULTS: Echocardiographic left
      ventricular mass index correlated significantly with arterial blood pressure,
      age, and body mass index. In addition, in men ACE activity was significantly
      related to left ventricular mass index in univariate (P = 0.0007) and
      multivariate analyses (P = 0.008). Men with left ventricular hypertrophy
      presented with significantly higher serum ACE concentrations than those with
      normal left ventricular mass index (P = 0.002). In both men and women serum
      aldosterone was strongly related to septal and posterior wall thickness.
      Furthermore, in women serum aldosterone was positively and independently
      associated with left ventricular mass index (P = 0.0001). This effect was most
      prominent in hypertensive women. Finally, women with left ventricular hypertrophy
      presented with significantly higher serum aldosterone (P = 0.01). No significant
      associations with left ventricular mass index were observed for angiotensinogen,
      renin, or pro-renin. CONCLUSIONS: The data suggest that the variability of serum
      ACE or aldosterone, as occurred in this large population based sample, may
      contribute to the modulation of left ventricular mass.

PMID- 9038693
TI  - Images in cardiology. A threatened paradoxical embolism.

PMID- 9038694
TI  - Recovery of atrial systolic function after pharmacological conversion of chronic
      atrial fibrillation to sinus rhythm: a Doppler echocardiographic study.
AB  - OBJECTIVE: To evaluate the time course of the recovery of atrial mechanical
      function after pharmacological cardioversion of chronic atrial fibrillation to
      sinus rhythm. PATIENTS AND METHODS: 21 patients (12 male, 9 female, aged 37-77
      years) with chronic atrial fibrillation (< 6 months) were followed up by serial
      transmitral pulsed Doppler echocardiography. Echocardiographic studies were
      performed within the first 24 hours and on day 8, 15, and 30 after cardioversion.
      RESULTS: There was a significant increase (mean (SD)) in the peak A-wave velocity
      (from 0.35 (0.10) on day 1 to 0.50 (1.73) on day 8, and thereafter a gradual
      increase to 0.61 (0.14) m/s on day 30). Similarly, integrated late atrial
      velocities increased from 4.50 (1.46) on day 1 to 5.61 (1.73) on day 8 and 5.97
      (1.47) cm/s2 on day 30. The atrial contribution to total transmitral flow
      increased significantly from 26 (7)% immediately after conversion of atrial
      fibrillation to sinus rhythm to 34 (7)% on day 30, indicating the haemodynamic
      benefit of the restoration of sinus rhythm. Left atrial diameter decreased but
      not significantly, from 4.11 (0.37) to 3.98 (0.34) cm (P < 0.005). CONCLUSIONS:
      These results suggest that restoration of atrial mechanical function after
      pharmacological cardioversion in patients with chronic atrial fibrillation is
      slow and gradual, as it is after electrical DC restoration of sinus rhythm. This
      time course may have important implications for determining how long treatment
      with anticoagulants and antiarrhythmic agents needs to continue in individual
      patients. It will also influence the clinical assessment of the haemodynamic
      benefit of restoring sinus rhythm in patients with chronic atrial fibrillation.

PMID- 9038696
TI  - Long-term outcome of electrical cardioversion in patients with chronic atrial
      flutter.
AB  - OBJECTIVE: To determine the long-term outcome of serial electrical cardioversion
      therapy in patients with chronic atrial flutter. DESIGN: Prospective study, case
      series. SETTING: University hospital. PATIENTS: 50 consecutive patients with
      chronic (> 24 hours) atrial flutter without a previous relapse on antiarrhythmic
      drugs. INTERVENTIONS: Elective electrical cardioversion therapy, if necessary
      repeated, to obtain and keep patients in sinus rhythm. If the first cardioversion
      resulted in sinus rhythm, patients were not given antiarrhythmic drugs. Relapses
      were managed by repeated cardioversions then anti-arrhythmic drugs were used
      serially in a set sequence. MAIN OUTCOME MEASURE: Maintenance of sinus rhythm.
      RESULTS: Mean (SD) follow up was 3.5 (1.7) years. The first cardioversion was
      successful in 48 patients (96%). After a single shock and without antiarrhythmic
      drugs being used, 42% of the patients maintained sinus rhythm in the long-term.
      Only left atrial size was inversely related to the efficacy of one shock (P =
      0.025). With serial cardioversion 90% of the patients were kept in sinus rhythm
      for 5 years. Univariate analysis showed that a long duration of arrhythmia and
      impaired cardiac function were both related to poor outcome. During follow up 3
      patients died of progression of heart failure and another 5 died suddenly. None
      of these 5 patients was on antiarrhythmic drugs. CONCLUSIONS: Electrical
      cardioversion was an effective and safe method of converting chronic atrial
      flutter to sinus rhythm. To maintain sinus rhythm, more than half of the patients
      required multiple shocks and prophylactic antiarrhythmic drugs. Sudden death was
      relatively frequent in the study population; the limited data available from this
      study suggest that such deaths were caused by the underlying disease and not drug
      related proarrhythmia.

PMID- 9038695
TI  - Electrocardiographic nature of restored sinus rhythm after Cox maze procedure in
      patients with chronic atrial fibrillation who also had other cardiac surgery.
AB  - OBJECTIVE: To characterise heart rate variability and high frequency components
      of restored sinus rhythm after the maze procedure. The maze procedure for chronic
      atrial fibrillation may prevent thrombotic events and improve the quality of
      life. However, the electrocardiographic nature of restored sinus rhythm after the
      maze procedure has not been fully elucidated. PATIENTS AND METHODS: Between March
      1993 and August 1995, 104 consecutive patients undergoing the maze procedure in
      combination with other cardiac surgery were studied. There were 100 long-term
      survivors (78 with mitral valve disease, 9 with aortic valve disease, 8 with
      congenital heart disease, and 5 others). Twenty age-matched patients with mitral
      valve disease who were in normal sinus rhythm preoperatively were enrolled as a
      control group. 30 days after surgery, the presence of arrhythmias and the
      circadian changes of heart rate variability were estimated by ambulatory
      electrocardiographic monitoring and the filtered P duration was evaluated by
      signal-averaged electrocardiogram. RESULTS: Restoration of sinus rhythm was
      observed in 73 of 100 cases. Subjects were classified into three groups according
      to their postoperative ambulatory electro-cardiographic monitoring findings:
      patients in group 1 (n = 73) (1a: 58 regular sinus rhythm; 1b: 15 sinus rhythm
      with frequent premature atrial contractions (> 1000/day); patients in group 2 (n
      = 21) still had persistent atrial fibrillation; and patients in group 3 (n = 6)
      required permanent pacemaker implantation because of sick sinus syndrome. The
      success rate of restoration of sinus rhythm was 88.3% if left atrial diameter was
      small (< 65 mm). Circadian changes in the low frequency to high frequency power
      ratio in group 1a were significantly diminished compared with control group (P <
      0.01). Furthermore, the filtered P duration in group 1a (150 (20) ms) and group
      1b (158 (23) ms) were longer than in the control group (122 (11) ms) (P < 0.01).
      CONCLUSIONS: The maze procedure may result in a decreased sinus response and non
      uniform transmission of impulses in the atrium.

PMID- 9038697
TI  - Cardiac autoantibodies in dilated cardiomyopathy become undetectable with disease
      progression.
AB  - OBJECTIVE: To determine the relation of cardiac autoantibody and disease status
      in a consecutive series of patients with dilated cardiomyopathy by prospective
      antibody testing at diagnosis and at follow up. METHODS: Antibody status was
      assessed by indirect immunofluorescence in 110 patients with dilated
      cardiomyopathy (85 male, mean (SD) age 44 (13) years) at diagnosis and at follow
      up (mean (SD) 14 (12) months); in 57 of them cardiac specific anti-alpha myosin
      antibody titres were also measured by an enzyme-linked immunosorbent assay
      (ELISA). Patients underwent complete evaluation at diagnosis and clinical and non
      invasive assessment at follow up, including exercise testing with maximal oxygen
      consumption measurements. RESULTS: The frequency of cardiac specific antibodies
      by immunofluorescence was lower at follow up than at diagnosis (28 (25%) v 11
      (10%), P = 0.002). Mean (SEM) anti-alpha myosin antibody titres at follow up were
      also lower than at diagnosis (0.24 (0.02) v 0.30 (0.02), P = 0.038); 24% of
      patients at diagnosis and 14% at follow up had an abnormal ELISA result. None of
      the patients who were negative by immunofluorescence or ELISA at diagnosis became
      positive at follow up. Presence of antibody at diagnosis was associated with
      milder symptoms and greater exercise capacity at follow up and persistence of
      antibody at follow up was associated with stable disease and milder symptoms at
      diagnosis. CONCLUSIONS: Cardiac specific autoantibodies in dilated cardiomyopathy
      become undetectable with disease progression; this is a recognised feature of
      other autoimmune conditions, such as type 1 diabetes. Detection of these
      antibodies at diagnosis and at follow up may provide a non-invasive marker of
      early dilated cardiomyopathy.

PMID- 9038698
TI  - Anatomical and echocardiographic correlates of normal cardiac morphology in the
      late first trimester fetus.
AB  - OBJECTIVES: To describe the normal cardiac morphology as seen by transvaginal
      ultrasound imaging in the first trimester fetus and to compare it with the
      morphology of the heart as seen by microdissection at the same gestational age.
      DESIGN: In 53 mothers undergoing early sonography, the fetal heart was examined
      and the images recorded. The gestational age range was 5-12 weeks of gestation,
      which represents 21 to 70 days after conception. Images were analysed frame by
      frame and compared with the anatomy of embryos and fetuses at the same
      gestational ages. RESULTS: After the 9th week of gestation, four cardiac
      chambers, the aortic origin, and the pulmonary artery could be identified on
      cross sectional echocardiography in conjunction with colour flow Doppler. At 9
      weeks, the apex pointed anteriorly and the right ventricle and pulmonary artery
      lay to the right of the midline. By the 11th week of gestation, the apex pointed
      to the left and the pulmonary artery lay to the left of the midline as in the
      older fetus. Between 9 and 12 weeks' gestation the aorta was larger than the
      pulmonary artery. These findings were confirmed in the microdissected hearts.
      CONCLUSIONS: The current quality of ultrasound images obtained using transvaginal
      transducers in the first trimester fetus allows the study of fetal cardiac
      anatomy. Some of the later developmental changes can be demonstrated. As
      technology improves further the details of earlier cardiac morphogenesis may also
      become visible.

PMID- 9038699
TI  - Intravascular ultrasound in patients with acute pulmonary embolism after
      treatment with intravenous urokinase and high-dose heparin.
AB  - OBJECTIVE: To compare the diagnostic value of intravascular ultrasound (IVUS)
      with angiography in patients with pulmonary embolism. DESIGN: Open, prospective
      clinical study. SETTING: Two university hospitals. PATIENTS: Angiography and IVUS
      were used in 11 patients (5 men) (mean (SD) age 50 (18) years) with acute
      pulmonary embolism. INTERVENTIONS: At a mean (SD) of 6 (4) hours after
      thrombolytic therapy with urokinase and full-dose heparin, all patients underwent
      pulmonary artery angiography. Then 3.5 F mechanical, 20 or 30 MHz IVUS catheters
      were advanced into the pulmonary circulation. MAIN OUTCOME MEASURES: The
      pulmonary circulation was studied by both methods to detect the presence of
      thrombus, and a modified Miller score (assessing perfusion defects only and not
      velocity of flow) was used to quantify the angiographic images. RESULTS: The
      modified Miller score was mean (SD) 7.4 (2.3) points. 168 pulmonary artery
      segments (diameter range 2-14 mm) were studied by angiography and IVUS. On
      angiography, seven segments showed complete obstruction and 49 partial
      obstruction; 112 were normal. Two distinct types of thrombus formation were found
      by IVUS. Type A thrombus only partly adhered to the wall but otherwise was mobile
      and type B predominantly adhered to the wall. IVUS confirmed all seven
      angiographically complete obstructions but missed three (6%) of the 49 partial
      occlusions. Forty (87%) of the remaining 46 segments had type A thrombus and six
      (13%) type B. IVUS indicated a thrombus in 38 (34%) of the 112 angiographically
      normal segments; 20 (53%) showed a type A pattern and 18 (47%) a type B pattern
      (P < 0.001). CONCLUSION: IVUS was more sensitive than angiography in detecting
      thrombus but the clinical impact of this finding is not clear as yet.

PMID- 9038700
TI  - Intracoronary demonstration of adenosine-induced coronary collateral steal.
AB  - A steal phenomenon was detected by intravascular Doppler guidewire in a patient
      with a well collateralised coronary vascular area supplied by a reopened left
      circumflex coronary artery. This phenomenon accounted for the fall in blood flow
      velocity reserve during hyperaemic conditions to 50% of the baseline value. The
      collaterals must have been the cause of the steal phenomenon because complete
      revascularisation of the lesion barely reversed it.

PMID- 9038701
TI  - Cardiac metastasis of an esthesioneuroblastoma.

PMID- 9038702
TI  - Complete heart block caused by cardiac echinococcosis and successfully treated
      with albendazole.

PMID- 9038703
TI  - Should balloon angioplasty be used instead of surgery for native aortic
      coarctation?

PMID- 9038704
TI  - Measuring outcomes: one month survival after acute myocardial infarction in
      Scotland.

PMID- 9038705
TI  - HIV-1-specific cell-mediated immunity is enhanced by co-inoculation of TCA3
      expression plasmid with DNA vaccine.
AB  - We developed a candidate DNA vaccine designated pCMV160IIIB with pcREV
      (pCMV160IIIB/REV) that encodes gp160 of human immunodeficiency virus (HIV)-1IIIB
      and Rev driven by the cytomegalovirus (CMV) promotor. This vaccine induced both
      HIV-1-specific antibodies and cytotoxic T lymphocyte (CTL) activity. In the
      present study, we inoculated the TCA3 expression plasmid into mouse skeletal
      muscle with pCMV160IIIB/REV to determine whether this cytokine expression plasmid
      was able to modify the immune response. Results of a delayed-type
      hypersensitivity (DTH) assay using footpad swelling as well as those of a CTL
      assay clearly demonstrated that cell-mediated immunity (CMI) elicited by co
      inoculation of pCMV160IIIB/REV with the TCA3 expression plasmid was markedly
      enhanced compared with that obtained using pCMV160IIIB/REV alone. When TCA3
      expression plasmid was inoculated with anti-TCA3 antibody, enhancement of the DTH
      response was suppressed below the level of that obtained with pCMV160IIIB/REV
      alone. The titre of HIV-1-specific IgG2a was slightly high when pCMV160IIIB/REV
      was co-inoculated with this plasmid, suggesting that T-helper 1 (Th1) response
      was predominant in TCA3-inoculated mice. Infiltration of mononuclear cells was
      seen in the muscles at sites where TCA3 expression plasmid had been inoculated.
      Our present data suggest that TCA3 expression plasmid has potent adjuvant
      activity that results in an augmented CMI response.

PMID- 9038706
TI  - Recovery from retrovirus-induced immune suppression in BDP/J mice: dominance of
      the "regressor' phenotype.
AB  - Murine acquired immune deficiency syndrome (MAIDS) is an immunosuppressive
      disease of mice induced by infection with the LP-BM5 murine leukemia virus (MuLV)
      retrovirus isolate. Certain inbred strains of mice are resistant to disease, but
      F1 crosses between sensitive and resistant strains are predominantly sensitive to
      MAIDS. One inbred strain, BDP, demonstrates a novel disease phenotype, recovery
      of immune function after a period of profound immune suppression. This trait is
      genetically dominant in crosses between BDP and either sensitive or resistant
      strains. The 'regressor' phenotype reveals the existence of a mechanism for
      recovery from immunosuppressive retrovirus infections, which may be of import in
      developing therapies for AIDS patients.

PMID- 9038707
TI  - Expression of HIS50 Ag: a rat homologue of mouse heat-stable antigen and human
      CD24 on B lymphoid cells in the rat.
AB  - Recently, a cDNA encoding a newly identified rat antigen (HIS50 Ag) that binds to
      monoclonal antibody (mAb) HIS50 was cloned and shown to be homologous to cDNA
      encoding murine heat-stable antigen (HSA) and human CD24. Here we show that, like
      CD24 and HSA, at least part of HIS50 Ag is inserted into the plasma membrane by a
      glycosylphosphatidylinosito: (GPI)-lipid linkage and we describe its expression
      in rat haemolymphopoietic tissues. HIS50 Ag expression was almost exclusively
      confined to B lymphoid cells, the vast majority of T lymphoid cells, erythroid
      and myeloid cells were HIS50+. Cell suspension analysis indicated that in bone
      marrow (BM) almost all Thy-1+ cells, HIS24+ cells [HIS24 recognizes the B-cell
      form of leucocyte common antigen (LCA)], terminal deoxynucleotidyl transferase
      positive (TdT+) cells and (c + s)kappa cells expressed HIS50 Ag, and all (c +
      s)mu 1 cells. A presumably early population of B lymphoid cells, expressing HIS24
      Ag without HIS50 Ag, TdT or immunoglobulin HIS24+HIS50+ TdT Ig+), constituted
      1.6% of BM nucleated cells. In blood, one-fifth of mononuclear cells were HIS50+,
      and about 85% of these expressed mu and/or kappa chains. In spleen, flow
      cytometry analysis and immunohistology demonstrated heterogeneous expression of
      HIS50 Ag: immunoglobulin M (IgM)bright cells (as found largely in red pulp and
      marginal zone) were HIS50bright, while IgMdull cells expressed low or
      undetectable levels of HIS50 Ag. Germinal centre B cells expressed high levels of
      HIS50 Ag. Germinal centres of lymph nodes and tonsil of man also bound HIS50. We
      conclude that HIS50 Ag expression in the haemolymphopoietic system of rat is
      virtually restricted to the B lineage.

PMID- 9038708
TI  - Locomotor properties of human germinal centre B cells: activation by anti-CD40
      and IL-4 allows chemoattraction by anti-immunoglobulin.
AB  - The locomotor properties of B cells isolated from the germinal centres (GC) of
      human tonsils were studied using polarization, collagen gel invasion and
      micropore filter assays. The proportion of motile GC cells in the freshly
      isolated population was small. During culture in interleukin-4 (IL-4)+anti-CD40,
      but not in control medium, the proportion of polarized cells increased and these
      cells migrated actively into collagen gels. After 24 hr culture, most of the
      surviving population was in locomotor morphology. The locomotor population
      consisted mainly of centrocytes in the G1 phase of growth. More locomotor cells
      than spherical cells took up [3H]uridine, but locomotor cells did not take up
      [3H]thymidine. After culture for 6 hr in IL-4+anti-CD40, GC B cells were tested
      in short-term polarization assays and filter assays for their response to
      chemoattractants. In both assays, a proportion of the cells responded to anti-IgA
      and to anti-IgA F(ab')2 fragments at 1 ng/ml., or to anti-IgG, anti-IgM and
      F(ab')2 fragments of these antibodies at 100 ng-1 microgram/ml. A checkerboard
      filter assay showed a good chemokinetic response and a weaker chemotactic
      response of GC cells to anti-IgA. Expression of Fc gamma RII (CD32) was increased
      after culture in IL-4+anti-CD40, and these cultured cells responded in filter and
      polarization assays to anti-CD32. Thus culture in IL-4 and anti-CD40 not only
      rescues GC B cells, but also increases their locomotor capacity and allows them
      to respond in chemotaxis assays to anti-immunoglobulin.

PMID- 9038709
TI  - Induction of murine CD5 expression by v-H-ras.
AB  - The murine CD5 surface antigen is a frequent marker on B-lineage cell lines
      produced from bone marrow infected with retroviruses expressing v-H-ras. Since
      CD5+ B cells cannot be detected in adult murine bone marrow, either the viral
      targets of transformation are a minor contaminating population of CD5+ B-lineage
      cells or the v-H-ras oncogene is inducing the expression of CD5 on B-lineage
      cells not previously expressing this marker. We have found that v-H-ras can
      induce the expression of CD5 on two CD5+ pre-B-cell lines established from murine
      bone marrow. This induction correlates with increased steady-state levels of CD5
      mRNA. These results present the possibility that CD5 expression may be modulated
      by specific signalling as well as early lineage commitment.

PMID- 9038710
TI  - Antigen-presenting cell-derived signals determine expression levels of CD70 on
      primed T cells.
AB  - Interaction between CD27 and its ligand CD70 provides a second signal for T-cell
      proliferation and tumour necrosis factor-alpha (TNF-alpha) production. Whereas
      CD27 is broadly expressed during T-cell development, expression of CD70 in vivo
      is restricted. To determine when CD27 CD70 interactions can occur in immune
      reactions, we here analysed the regulation of CD70 expression on activated T
      cells. Mitogenic stimulation of purified T cells with either immobilized CD3
      monoclonal antibody (mAb) or a combination of CD2 mAb induces only low levels of
      CD70 membrane expression. Markedly expression of the CD27-ligand is strongly
      enhanced by antigen-presenting cells (APC) and APC-associated signals such as
      interleukin-1 alpha (IL-1 alpha). IL-12, TNF-alpha and CD28-ligation. In
      contrast, T-cell derived cytokines, such as IL-4, counteract CD70 up-regulation
      on activated T cells. Analysis of the small subset of circulating CD70+ T cells
      revealed that these cells have a primed phenotype as they express CD45RO and HLA
      DR antigens and are in high frequency able to secrete interferon-gamma (IFN
      gamma). We conclude that T-T interactions involving CD27 and CD70 are likely to
      occur relatively early in immune reactions, after productive T-cell priming by
      APC and that expression of CD70 on circulating T cells is a reflection of recent
      priming by antigen.

PMID- 9038711
TI  - Vaccination with a multi-epitopic recombinant allergen induces specific immune
      deviation via T-cell anergy.
AB  - Prophylactic vaccination has recently emerged as a major paradigm toward the
      prevention and therapy of allergies and asthma; however, the immunological basis
      of this approach remains to be elucidated. We examined the potential and
      mechanism of prophylaxis of allergic response in B6D2F1 mice with a multi
      epitopic recombinant allergen, rKBG8.3 (MERA-8.3), which represents a major group
      of allergens of grass pollens, used herein as a model of MERA vaccine.
      Vaccination (subcutaneous) with soluble MERA-8.3, prior to immunization with the
      MERA-8.3 in alum, led to suppression of the IgE antibody response and a
      concomitant increase in IgG2a antibody response specific to the MERA-8.3 in a
      dose-dependent manner. Analysis of cytokine patterns in spleen and lymph node
      cells revealed a marked decrease of interleukin-2 (IL-2) and IL-4 production and
      to a lesser extent a decrease of interferon-gamma (IFN-gamma) synthesis,
      resulting in an increased ratio of IFN-gamma: IL-4 in vaccinated-immunized mice
      compared with untreated-immunized control mice. Furthermore, splenocytes of mice
      treated with the MERA-8.3 alone proliferated to MERA-8.3 in vitro with reduced
      capacity compared with the splenocytes of MERA-8.3-alum immunized mice, owing to
      a markedly reduced level of IL-2 production in the former. Collectively, these
      results suggest that vaccination with the MERA-8.3 induces T-cell anergy, which
      is pivotal to deviation of specific immunity from Th2- to Th1-like, and may serve
      as an important approach to prevention and therapy of allergic disorders.

PMID- 9038712
TI  - Delayed-type hypersensitivity elicited by synthetic peptides complexed with
      Mycobacterium tuberculosis hsp 70.
AB  - Four synthetic peptides bearing dominant CD4+ T-cell epitopes of the 19,000 and
      38,000 MW proteins of Mycobacterium tuberculosis were used to provoke a delayed
      type hypersensitivity (DTH) reaction in mice previously immunized with
      recombinant 19,000 and 38,000 MW proteins. It was found that an effective
      enhancement of the DTH reaction was obtained if the peptides were administered as
      a complex with M. tuberculosis hsp 70 protein. The increase in reactivity was not
      obtained when hsp 70 and peptide were co-injected at the same site, but not in
      complex, or when the specific peptide was displaced from the complex by an
      irrelevant peptide with high capacity to bind hsp 70. One of the antigenic
      peptides whose capacity to complex with hsp 70 is low, failed to show the
      enhancement of DTH when injected together with hsp 70.

PMID- 9038713
TI  - Desialylation of T lymphocytes overcomes the monocyte dependency of pokeweed
      mitogen-induced T-cell activation.
AB  - Activation of T lymphocytes by pokeweed mitogen (PWM) is strictly monocyte (Mo)
      dependent and results in T-cell mitogenesis and interleukin-2 (IL-2) secretion,
      coupled with an inability to utilize IL-2 due to an impaired expression of
      functional IL-2 receptor (IL-2R). Such IL-2R impairment could arise in PWM
      activated T cells themselves or, alternatively, be the result of Mo-derived
      influences, as it is known that PWM binds Mo strongly and does not or poorly
      binds lymphocytes, and Mo becomes rapidly destroyed in PWM-stimulated cultures of
      blood mononuclear cells or T cells plus Mo. The present study investigated these
      possibilities. The results show for the first time that desialylation of T
      lymphocytes strongly increases their PWM-binding capacity and, in addition,
      overcomes the Mo requirement for PWM to induce T-cell mitogenesis and IL-2
      secretion. Such secreted IL-2 levels were even higher that those found in
      cultures of Mo-dependent PWM-activated T lymphocytes but similarly to the latter,
      PWM-activated desialylated purified T lymphocytes exhibited negligible high
      affinity IL-2 binding capacity and an inability to utilize the IL-2 they
      produced. These effects were not due to desialylation itself, as indicated by
      data obtained with peanut agglutinin, a lectin that becomes strongly reactive
      with desialylated T lymphocytes. The data clearly indicate the existence of PWM
      related events capable of impairing the expression of functional IL-2R without
      affecting IL-2 secretion, and indicate that such events are due to mechanisms
      arising at the level of PWM-activated T cells themselves.

PMID- 9038714
TI  - Glucocorticoids enhance concanavalin A-induced mitogenic response through the
      inhibition of nitric oxide production.
AB  - Glucocorticoids (GC) are known to inhibit mitogen-induced proliferation of T
      cells. In this study we show two experimental situations where the addition of GC
      increases lymphocyte proliferation. It has been reported by different authors
      that rat spleen (SPL) cells proliferate poorly after concanavalin A (Con A)
      activation. These poor responses have been related to the suppressor activity of
      macrophages. Similarly, it is known that T-cell proliferation is depressed in the
      presence of an excess of macrophages in the culture. Here we show that in both
      experimental situations, the inclusion of dexamethasone (DEX), a synthetic
      glucocorticoid, in the culture medium enhances the Con A-stimulated
      proliferation. We provide evidence that this effect is a consequence of the
      inhibition of nitric oxide (NO) synthesis by the hormone. Furthermore, we also
      demonstrate that rat SPL cells are inefficient antigen-presenting cells (APC)
      because of their spontaneous high production of NO. Taken together our results
      suggest that the effects of GC on T-cell activation may be to promote or inhibit
      proliferation depending on the level of endogenous NO synthesis. The possible
      significance of these results is briefly discussed.

PMID- 9038715
TI  - T-cell stimulation and cytokine release induced by staphylococcal enterotoxin A
      (SEA) and the SEAD227A mutant.
AB  - Previous work demonstrated that human cytotoxic T cells activated by
      superantigens can lyse major histocompatibility complex (MHC) class II-positive
      target cells as well as MHC class II-negative tumour cells coated with conjugates
      of monoclonal antibodies and superantigens. In order to decrease MHC class II
      affinity, and therefore unwanted binding of the superantigen staphylococcal
      enterotoxin A (SEA) to MHC class II molecules, a point mutation was introduced
      into the SEA gene. This mutation (SEAD227A) resulted in an approximately 3-log
      reduction of affinity to human leucocyte antigen (HLA)-DR, but cytotoxicity
      mediated by this mutant superantigen towards antibody-labelled tumour cells is as
      efficient as cytotoxicity mediated by the native superantigen. We therefore
      compared the T-cell activating potency of native and mutated SEA. Our data show
      that SEAD227A is 4- to 5-log less effective than native SEA when activation of
      resting T cells is assayed in terms of blast formation, expression of cell
      surface activation markers and cytokine release. Furthermore, presenting either
      SEA or SEAD227A to MHC class II-negative mononuclear cells by MHC class II
      negative tumour cells did not result in significant blast formation of T cells,
      up-regulation of CD25 or cytokine release. This suggests that lysis of MHC class
      II-negative tumour cells is efficiently induced by monoclonal antibody targeted
      superantigen, while activation of resting T cells requires additional co
      stimulatory signals.

PMID- 9038716
TI  - Pristane-induced arthritis is CD4+ T-cell dependent.
AB  - The development of arthritis induced in mice by intraperitoneal injection of the
      non-antigenic mineral oil pristane (2,6,10,14-tetramethylpentadecane) was shown
      to depend on the presence of CD4+ T cells. Initial experiments assessed the
      influx of lymphoid cells into the peritoneal cavity of CBA/Igb mice after
      pristane injection. Both CD4+ and CD8+ cell numbers were maximal around 50 days.
      Other experiments confirmed our original observation that irradiated pristane
      treated mice failed to develop arthritis unless they were reconstituted with
      spleen cells from normal donors. This finding has been extended by showing that
      the population of transferred splenic lymphoid cells must contain CD4+ T cells,
      while CD8+ T cells and B cells were not required for reconstitution.
      Conventionally housed and hsp 65-immunized animals are known to harbour T cells
      reactive with hsp 65. In addition, hsp 65-immunized mice are resistant to the
      development of pristane-induced arthritis (PIA). Thus, additional experiments
      assessed the population of splenic T cells activated and proliferating against
      mycobacterial 65,000 MW heat shock protein (hsp 65). In cultures of purified
      splenic T cells derived from both conventional and hsp 65-immunized mice, removal
      of CD4+ T cells significantly reduced the proliferative response to hsp 65, while
      removal of CD8+ T cells often enhanced the response. These proliferative
      responses were also shown to be major histocompatibility complex (MHC) class II
      restricted. The present findings demonstrate that PIA is CD4+ T-cell mediated,
      and immunodominant environmental antigens such as hsp 65 activate this population
      of lymphocytes. The CD4+ hsp 65-reactive population may be pathogenic or
      protective in PIA, depending upon the route of sensitization.

PMID- 9038717
TI  - Localization of IL-4 and IL-4 receptors in the human term placenta, decidua and
      amniochorionic membranes.
AB  - There has been much recent interest in cytokine expression at the materno-fetal
      interface. Although T-helper 2 (Th2)-type cytokines have been described in the
      murine feto-placental unit, few studies have as yet been performed in human
      pregnancy. We have examined the production of interleukin-4 (IL-4) and expression
      of IL-4 receptors in the human term placenta, decidua and amniochorionic
      membranes. Immunohistochemical analyses revealed that cytotrophoblast, decidual
      macrophages and both maternal and fetal endothelial cells consistently expressed
      IL-4, whereas syncytiotrophoblast and placental macrophages showed an
      inconsistent pattern between specimens. High- and low-affinity IL-4 receptors
      were demonstrated by immunohistochemistry at the same cellular sites as stained
      for IL-4, and detection of IL-4 receptors was also variable in
      syncytiotrophoblast. Reverse-transcribed-polymerase chain reaction (RT-PCR)
      analysis showed that both IL-4 and its alternative splice variant, IL-482, are
      produced both in placental villi and in amniochorionic and decidual tissue.
      Ligand-binding assays identified the presence, on isolated term
      syncytiotrophoblast microvillous plasma membrane vesicle preparations, of
      functional high-affinity binding sites for IL-4 with a Kd in the range 102-112 pM
      and an apparent receptor density in the range 99-102 x 10(8) sites/mg protein.
      Three human choriocarcinoma (BeWo, JEG-3 and Jar) and one amnion-derived (AV3)
      cell lines expressed IL-4 and both high- and low-affinity IL-4 receptors. The
      constitutive expression of both IL-4 and IL-4 receptors, together with the novel
      finding of the alternative splice variant IL-482 in the immediate tissues at the
      materno fetal interface suggest an immunobiological role for IL-4 in human
      pregnancy.

PMID- 9038718
TI  - Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and
      nitric oxide production and protects against the development of vascular
      hyporeactivity in endotoxaemia.
AB  - Pro-inflammatory cytokines, such as tumour necrosis factor (TNF) and free
      radicals, such as nitric oxide (NO), are mediators of endotoxaemia.
      Catecholamines are in clinical use to treat the haemodynamic consequences of
      severe septic shock. Beta-adrenergic agonists exert many of their effects by
      elevation of intracellular cyclic AMP (cAMP) concentration. Cyclic AMP can
      modulate endotoxin-induced cytokine and NO production. Here we investigate the
      effect of isoproterenol pretreatment on the cytokine and NO production induced by
      bacterial lipopolysaccharide (LPS, 4-10 mg/kg). Pretreatment with isoproterenol
      (10 mg/kg) blunted the LPS-induced TNF response, increased the LPS-induced
      formation of interleukin-10 and interleukin-6 and reduced the LPS-induced
      production of NO in conscious mice. In anaesthetized rats, pretreatment with
      isoproterenol prevented the LPS-induced suppression of vascular contractility to
      norepinephrine in the thoracic aorta ex vivo. The hyporeactivity is due to
      expression of the inducible isoform of NO synthase (iNOS) and was restored by in
      vitro administration of NG-methyl-L-arginine (L-NMA), an inhibitor of NO
      synthase. However, L-NMA did not alter vascular contractility in control vessels
      or in rings taken from the LPS-treated rats pretreated with isoproterenol. Our
      findings suggest that, in addition to its haemodynamic actions, isoproterenol may
      also exert beneficial effects by modulating the endotoxin-induced inflammatory
      response.

PMID- 9038719
TI  - The beneficial effects of treatment with tamoxifen and anti-oestradiol antibody
      on experimental systemic lupus erythematosus are associated with cytokine
      modulations.
AB  - In an attempt to elucidate the role of oestrogens in systemic lupus erythematosus
      (SLE) we investigated the effects of treatment with an oestrogen antagonist
      tamoxifen and a monoclonal anti-oestradiol (anti-E2) antibody on mice in which
      experimental systemic lupus erythematosus (SLE) was induced by a human monoclonal
      anti-DNA antibody bearing the 16/6 idiotype (16/6 Id). Thus, groups of BALB/c
      female mice were immunized with the 16/6 Id and 3 weeks following the booster
      injection, when antibody titres were elevated in the injected mice, treatment
      protocols with anti-oestradiol or tamoxifen were initiated. Control groups that
      were not immunized with the 16/6 Id but were similarly treated with the above
      agents were included in the study. The treatment with the above agents had no
      effect on the total autoantibody titres; however, a decrease in the
      immunoglobulin G (IgG)2a/IgG1 ratio of the anti-DNA antibodies was determined in
      the 16/6 Id immunized and treated mice. Further both the anti-oestradiol and
      tamoxifen had beneficial effects on the clinical manifestations (white blood cell
      counts, levels of protein in the urine and immune complex deposits in the
      kidneys) of the 16/6 Id immunized and treated mice. We have previously observed a
      significant elevation in interleukin-1 (IL-1) and tumour necrosis factor-alpha
      (TNF-alpha) secretion in mice with experimental SLE and a reduction in IL-2, IL-4
      and interferon-gamma (INF-gamma) levels as compared with the levels detected in
      healthy controls. Treatment with either the anti-oestradiol antibody or with
      tamoxifen restored the levels of all the above cytokines to the normal levels
      observed in the control mice. These findings suggest that cytokine modulation may
      be the basis for the therapeutic effects of both anti-oestrogens in experimental
      SLE.

PMID- 9038720
TI  - A human CD4+ T-cell line expresses functional CD64 (Fc gamma RI), CD32 (Fc gamma
      RII), and CD16 (Fc gamma RIII) receptors but these do not enhance the infectivity
      of HIV-1-IgG complexes.
AB  - T cells do not generally express Fc receptors (FcRs). However, we report here
      that C8166 cells, a human CD4+ T lymphoblastoid cell line, widely used in
      research into the human immunodeficiency virus type 1 (HIV-1), expressed CD64 (Fc
      gamma RI), CD32 (Fc gamma RII), and CD16 (Fc gamma RIII) on the plasma membrane
      as shown by immunostaining with specific monoclonal antibody fragments. Another
      human CD4+ T lymphoblastoid cell line. H9, expressed none of these FcRs. C8166
      cells bound monomeric normal rat serum IgG in a dose-dependent manner, and when
      saturated bound heat-complexed immunoglobulin G (IgG) also dose dependently.
      These observations are consistent with the presence on the C8166 T-cell line of
      both high- and low-affinity Fc gamma Rs. Fc gamma Rs are putative receptors for
      virus-IgG complexes, but in this study did not enhance infectivity of HIV-1
      complexed with a human neutralizing mAb or three rat neutralizing mAbs. Virus
      complexed with a non-neutralizing mouse mAb was unable to infect cells using Fc
      gamma Rs as receptors after CD4 was blocked with a specific anti-CD4 mAb.

PMID- 9038722
TI  - Binding of human and rat CD59 to the terminal complement complexes.
AB  - CD59-antigen (protectin) is a widely distributed glycolipid-anchored inhibitor of
      complement lysis. CD59 interacts with complement components C8 and C9 during
      assembly of the membrane attack complex (MAC). To evaluate species specificity of
      these interactions we have in the present study examined cross-species binding of
      isolated human and rat CD59 to the terminal complement components C8 and C9. By
      using primarily soluble CD59 isolated from urine (CD59U) potentially non-specific
      binding interactions of the phospholipid portion of the membrane forms of CD59
      could be avoided. Sucrose density gradient ultracentrifugation analysis showed
      that human CD59U bound to both human and rat C8 in the SC5b-8 complexes. Similar
      binding occurred when rat CD59U was used. The degree of binding did not
      significantly differ between the heterologous and homologous CD59-C8
      combinations. C9 from both species inhibited the binding of CD59 to soluble SC5b
      8. In ligand blotting analysis human and rat CD59U bound to human and rat C8
      alpha gamma-subunit and C9. Binding of human and rat CD59U was stronger to human
      than rat C9. In plate binding assays the erythrocyte form of CD59 (CD59E) bound
      to both human and rat C8. Binding of CD59E to heterologous C9 was considerably
      weaker than to homologous C9. Our results imply that the reciprocal binding sites
      between C8 and CD59 and to a lesser degree between CD59 and C9 are conserved
      between human and rat. Interactions of CD59 with the terminal C components are
      thus species selective but not 'homologously restricted'.

PMID- 9038721
TI  - Inhibition of human complement by beta-glycyrrhetinic acid.
AB  - Licorice, the root extract of Glycyrrhiza glabra I., is used as a medicine for
      various diseases. Anti-inflammatory as well as anti-allergic activities have been
      attributed to one of its main constituents, glycyrrhizin. These activities are
      mainly ascribed to the action of the aglycone, beta-glycyrrhetinic acid. beta
      Glycyrrhetinic acid has a steroid-like structure and is believed to have
      immunomodulatory properties. To determine whether interference with complement
      functions may contribute to the immunomodulatory activity of beta-glycyrrhetinic
      acid, its effects on the classical and alternative activation pathways of human
      complement were investigated. We found that beta-glycyrrhetinic acid is a potent
      inhibitor of the classical complement pathway (IC50 = 35 microM), whereas no
      inhibitory activity was observed towards the alternative pathway (IC50 > 2500
      microM). The anticomplementary activity of beta-glycyrrhetinic acid was dependent
      on its conformation, since the alpha-form was not active. It was also established
      that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not
      inhibit human complement activity under similar conditions. Detailed mechanistic
      studies revealed that beta-glycyrrhetinic acid acts at the level of complement
      component C2.

PMID- 9038723
TI  - The role of complement receptor type 1 (CR1, CD35) in determining the cellular
      distribution of opsonized immune complexes between whole blood cells: kinetic
      analysis of the buffering capacity of erythrocytes.
AB  - Erythrocytes (E) express complement receptor, type 1 (CR1, CD35), by which they
      bind opsonized immune complexes (IC) in competition with leucocytes expressing
      higher numbers of CR1 as well as other complement- and Fc-receptors. This may
      prevent inappropriate activation of phagocytic cells. We examined the
      distribution on whole blood cells of preformed tetanus toxoid (TT)/human anti-TT
      IC, opsonized in situ in 80% autologous serum. Binding to E occurred rapidly and
      reflected the kinetics of C3-fragment incorporation into the IC. Among eight
      donors, expressing 180-361 CR1 per E. > 90% of the cell-bound IC were associated
      with E from 1 to 5 min of incubation, decreasing to 12 +/- 13% after 40 min. Upon
      comparison of the IC-binding to leucocytes in whole blood with that of isolated
      leucocytes we found that E, despite their extensive early complex uptake, only
      reduced the IC-deposition on polymorphonuclear leucocytes (PMN) by 61 +/- 26%
      after 30 seconds of incubation and 47 +/- 14% after 5 min. During the subsequent
      10 min, this buffering capacity of E was essentially abolished E restricted the
      initial IC-binding to B cells by 73 +/- 19%, but from 3 min of incubation the
      presence of E promoted, in a CR1-dependent manner, a progressive uptake via CR2
      by the B cells. CR1 was the dominant receptor in the early IC-uptake by B cells
      as well as PMN and monocytes, since CR1-blockade inhibited the initial IC-uptake
      by these populations in a preparation of isolated leucocytes suspended in serum
      by > or = 84% after 30 seconds of incubation. We conclude, that E exert a
      substantial buffering effect on the IC-deposition on PMN, monocytes and B cells,
      while CR1 is the dominant receptor in the uptake by these cells. However, this
      effect is short-lived and less than expected from the proportion of IC bound to
      E. Moreover, E are efficient processors of IC-attached C3b/iC3b fragments to C3dg
      as indicated by a pronounced enhancement by E of IC-uptake via CR2 on B cells. We
      propose that this mechanism may play a role in preventing phagocyte activation
      via CR3.

PMID- 9038724
TI  - Human dendritic cells handling of binding, uptake and degradation of free and IgG
      immune complexed dinitrophenylated human serum albumin in vitro.
AB  - The handling of free and IgG-complexed dinitrophenylated human serum albumin (DNP
      HSA) by human dendritic cells (DC) cultured with granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin-4 (IL-4) was studied. It has been
      shown that the amount of uncomplexed or IgG-complexed antigen required by DC to
      start an immune response is low compared with other antigen-presenting cells. We
      therefore examined whether such efficient presentation of immune complexes is due
      to an enhanced Fc gamma RII-mediated endocytosis or to a specialized and
      efficient antigen handling, i.e., macropinocytosis. The Fc gamma RII expression
      was found to be heterogeneous on the GM-CSF- and IL-4-cultured DC, i.e. it ranges
      from low to high expression. The handling of antigen and immune complexes
      revealed, that the level of binding and uptake of IgG-DNP-HSA complexes by in
      vitro expanded DC is low compared with free antigen. Uncomplexed DNP-HSA is
      probably handled either by endocytosis via receptors being more abundant and/or
      efficient than the Fc gamma RII or via non-receptor-mediated endocytosis. The
      binding and uptake of IgG-complexed DNP-HSA was blocked by anti-Fc gamma RII
      antibody, indicating the specificity of the interaction.

PMID- 9038727
TI  - Proliferation in the normal cervix and in preinvasive cervical lesions.

PMID- 9038726
TI  - Diadenosine polyphosphates induce intracellular Ca2+ mobilization in human
      neutrophils via a pertussis toxin sensitive G-protein.
AB  - The diadenosine polyphosphates diadenosine 5',5"'-P1,P3-triphosphate (Ap3A),
      diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), diadenosine 5',5"'-P1,P5
      pentaphosphate (Ap5A) and diadenosine 5',5"'-P1,P6-hexaphosphate (Ap6A) all
      stimulated increases in intracellular Ca2+ in human neutrophils. Maximal
      increases in intracellular Ca2+ of 650 nM were obtained at dinucleotide
      concentrations of 500-700 microM. These increases in intracellular, Ca2+ were
      completely abolished by pre-treatment of the neutrophils with pertussis toxin and
      were hardly affected when the extracellular buffer was devoid of Ca2+. On the
      other hand, adenosine triphosphate (ATP) could stimulate much greater increases
      in intracellular Ca2+ (up to 1.1 microM) at much lower concentrations (half
      maximal responses obtained at around 5 microM ATP). Receptor de-sensitization
      experiments indicate that human neutrophils may possess two types of P2
      purinoceptors. The first of these may bind ATP (but not the dinucleotides) with
      high affinity whilst the second may bind the dinucleotides with lower affinity
      and also bind ATP.

PMID- 9038725
TI  - CD44-stimulated dendrite formation ('spreading') in activated B cells.
AB  - A rat monoclonal antibody (mAb) (NIM-R8), insolubilized by binding to plastic
      plates, induced a rapid and extensive formation of dendrite processes
      ('spreading') in B lymphocytes activated by anti-IgM and interleukin-4 (IL-4) or
      anti-CD38 and IL-4. In contrast, resting B cells were unable to spread similarly
      on the NIM-R8-coated plates. The NIM-R8 antibody recognized a 90,000 MW surface
      glycoprotein (gp90) present on both B and T lymphocytes. The expression of this
      molecule was greatly increased after polyclonal (lipopolysaccharide, anti-IgM
      plus IL-4 or concanavalin A) activation. The NIM-R8 mAb with or without IL-2 or
      IL-4 was unable to induce proliferation of splenic lymphocytes. Following the
      demonstration that the NIM-R8 mAb recognizes the murine equivalent of human CD44,
      the induction of spreading of activated B lymphocytes was studied using a panel
      of mAb recognizing different epitopes of murine CD44. All of these different mAb
      induced similar spreading of activated B cells. The ligand-inducible spreading of
      activated B lymphocytes may be an important mechanism for providing an increased
      cell-surface area for cell-cell or cell-matrix interactions, and thus may be an
      important factor controlling the response of activated lymphocytes.

PMID- 9038728
TI  - Hyperfibrinolysis.

PMID- 9038729
TI  - Viral gastroenteritis: small round structured viruses, caliciviruses and
      astroviruses. Part II. The epidemiological perspective.

PMID- 9038730
TI  - Origins of .... the postmortem examination in diagnosis.

PMID- 9038731
TI  - Serum and tissue measurements of CA72-4 in patients with endometrial carcinoma.
AB  - AIMS: To evaluate the clinical usefulness of CA72-4 as a serum tumour marker for
      endometrial carcinoma and to investigate its immunohistochemical localisation in
      endometrial carcinoma cells. METHODS: Serum concentrations of CA72-4 were
      determined in 72 patients with endometrial carcinoma. Immunohistochemical
      localisation of CA72-4 was investigated using the streptavidin-biotin method,
      using monoclonal antibodies B72.3 and CC49. RESULTS: Serum CA72-4 was increased
      above the cut off value in 31.9% of the patients with endometrial carcinoma.
      Serum CA72-4 positivity was correlated with depth of myometrial invasion, adnexal
      metastasis, lymphovascular space involvement, and pelvic and para-aortic lymph
      node metastasis. Multivariate analysis showed a significant correlation between
      serum CA72-4 positivity and adnexal metastasis. The serum concentrations of CA125
      and CA19-9, which could be tumour markers for endometrial carcinoma, were
      measured at the same time. In seven of 72 patients increased concentrations of
      serum CA72-4 were found while those for CA125 and CA19-9 were within the normal
      ranges; in four of the seven patients the disease had spread beyond the uterus.
      Immunohistochemical positivity for CA72-4 antigen was 76.9% and occurred in the
      tumour cell membrane and cytoplasm. There was no significant difference in
      immunohistochemical positivity between patients with increased CA72-4 and those
      with normal CA72-4 values. CONCLUSIONS: The measurement of serum concentrations
      of CA 72-4 could be useful for predicting and monitoring the progress of disease
      for example, extracorporeal spread.

PMID- 9038732
TI  - p53 expression in carcinoma of the cervix.
AB  - AIM: To assess overexpression of the proposed tumour suppressor gene product p53
      using the mouse monoclonal antibody DO-7 in the three main subtypes of carcinoma
      of the uterine cervix and to evaluate its value as a prognostic indicator.
      METHODS: Eighty two cases of FIGO Stage IB/IIA uterine cervical carcinoma were
      studied retrospectively. The tumours had been previously typed into
      adenocarcinomas, squamous carcinomas and adenosquamous carcinomas after the
      tissue had been fixed in formalin and embedded in paraffin wax. p53 protein
      expression was assessed using a standard immunohistochemical technique and the
      findings were correlated with tumour type, lymph node status and clinical
      outcome. RESULTS: In total, the p53 gene product was overexpressed in 17.1%
      (14/82) of all carcinomas and also in areas of cervical intraepithelial neoplasia
      grade III adjacent to invasive squamous carcinoma. Where present, the normal
      epithelium was uniformly negative. No association was found between p53
      overexpression and tumour subtype, lymph node status or clinical outcome.
      CONCLUSIONS: It seems unlikely that p53 analysis will be of value in determining
      prognosis in carcinoma of the uterine cervix.

PMID- 9038733
TI  - Use of flow cytometry in the analysis of stage III squamous cell carcinoma of the
      oesophagus and its association with MIB-1.
AB  - AIMS: To examine the prognostic and pathobiological importance of DNA content in
      oesophageal squamous cell carcinomas in Hong Kong Chinese subjects; to evaluate
      its association with the immunohistochemical proliferative marker MIB-1. METHODS:
      Paraffin wax embedded tumour tissue and adjacent normal tissue (control tissue)
      samples from 45 resected stage III oesophageal squamous cell carcinomas were
      studied using flow cytometric analysis. The DNA content and the
      clinicopathological data of these patients were analysed together with the MIB-1
      labelling index. RESULTS: DNA aneuploidy was present in 14 (31%) of the 45 cases.
      However, the DNA content did not correlate significantly with the age, sex, or
      survival of the patients, nor the length, location, differentiation and MIB-1
      labelling index of the oesophageal carcinomas. The synthetic (S) phase fraction
      of diploid tumours bore no relation to the patients' survival or MIB-1 score.
      CONCLUSIONS: Flow cytometry was not as useful as the MIB-1 labelling index in
      predicting the biological characteristics of the tumours and the prognosis of
      patients with oesophageal squamous cell carcinomas. This study does not support
      the routine use of DNA flow cytometric analysis in oesophageal cancers.

PMID- 9038734
TI  - Risk of gastric carcinoma in patients with mucosal dysplasia associated with
      atrophic gastritis: a follow up study.
AB  - AIMS: To assess the risk of gastric carcinoma in patients with histologically
      verified dysplasia and atrophic gastritis of the stomach. METHODS: One hundred
      and one patients with mild (n = 84), moderate (n = 14), or severe (n = 3)
      dysplasia among 359 elderly men who smoked underwent gastroscopy because of low
      serum pepsinogen. Patients with dysplasia were prospectively followed up for an
      average of four years with repeated gastroscopies and multiple biopsies. RESULTS:
      Four of the 84 (4.8%) cases of mild dysplasia had progressed to moderate
      dysplasia during the follow up. Most of the cases of mild dysplasia had resolved
      spontaneously. No surgical intervention was required. Three of the 14 (21%) cases
      of moderate dysplasia had progressed to severe dysplasia, but no carcinomas were
      observed during follow up. Five moderately dysplastic lesions were removed
      surgically or endoscopically. In two of these five cases, moderate or severe
      dysplasia recurred. Two of the three severe dysplasias progressed to carcinoma.
      CONCLUSIONS: In atrophic gastritis progression of mild and moderate dysplastic
      lesions seems to be a slow process and is rare in mild dysplasia. However, severe
      dysplasia is highly predictive of subsequent cancer. It is suggested that a five
      year follow up interval is sufficient in cases with mild dysplasia and two years
      in those with moderate dysplasia. Local removal of moderate dysplasia is
      indicated but does not guarantee that the lesion will not progress. Severe
      dysplasia requires immediate surgical intervention.

PMID- 9038735
TI  - Severe xanthomatosis associated with familial apolipoprotein E deficiency.
AB  - AIM: To present the clinical, dermatological, and histological features of a
      patient with generalised xanthomatosis, familial apolipoprotein (apo) E
      deficiency, and unusual type III hyperlipoproteinaemia (HLP). METHODS: The
      underlying molecular defect was disclosed using molecular biological techniques.
      The unusual xanthomas were histologically analysed and the morphology of the
      abnormal lipoprotein particles examined using electron microscopy. RESULTS: A 10
      base pair deletion in exon 4 of the proband's apo epsilon gene (base pairs 4037
      4046 coding for amino acids 209-212 of the mature protein) was identified. This
      is predictive for a reading frameshift encoding a premature stop (TGA) in codon
      229. The mutation is responsible for delayed catabolism of atherogenic
      lipoprotein remnants, lipid storage in monocyte/macrophages, and phenotypic
      expression of xanthomatosis early in life. CONCLUSIONS: Familial apo E deficiency
      is a rare genetic disease which offers the unique opportunity to study the impact
      of apo E on lipoprotein metabolism and development of atherosclerosis in humans.

PMID- 9038736
TI  - Hyperfibrinolysis in hepatosplenic schistosomiasis.
AB  - AIM: To evaluate the nature of accelerated fibrinolysis in hepatosplenic
      schistosomiasis. METHODS: The biological activity of plasminogen (Plg),
      plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen
      activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15
      compensated and 35 decompensated patients with endemic Egyptian
      hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t
      PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP),
      fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin
      complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody
      sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic
      insufficiency according to the Child-Pugh classification, were also carried out.
      RESULTS: The progressive deterioration of liver function in schistosomal
      patients, which matched the severity of the disease, led to simultaneous defects
      in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic
      (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most
      prominent-resulting in significant generation of plasmin (increased APP
      complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The
      raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary
      nature. CONCLUSION: These findings suggest that the amount of PAI-1 available to
      bind and neutralise circulating t-PA may be a critical factor in the progress of
      hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the
      pronounced reduction in its plasma concentration may be regarded as a potential
      warning indicator of haemostatic imbalance in decompensated schistosomal patients
      at high risk of variceal bleeding.

PMID- 9038737
TI  - Assessment of commercial enzyme immunoassay for hepatitis C virus serotyping.
AB  - AIMS: To assess a commercial enzyme immunoassay (EIA) for the serotyping of
      hepatitis C virus (HCV) for routine use in a diagnostic laboratory setting, as
      well as for noting the serotype prevalence of selected specimens. METHODS:
      Seventy six serum specimens, submitted to the laboratory for routine hepatitis
      studies between May 1992 and February 1996 and stored at -20 degrees C, were
      evaluated. These specimens were categorised into specific hepatic, renal, and
      paediatric clinical conditions. The specimens all tested positive for HCV
      antibodies on a screening EIA, with confirmation on a recombinant immunoblot
      assay (RIBA). Certain specimens were also HCV RNA positive by the reverse
      transcription polymerase chain reaction (RT-PCR). All the specimens were
      serotyped using the newly developed serotyping EIA. RESULTS: Twenty seven (35.5%)
      specimens were typable. Type 5 predominated (56%), followed by type 1 (33%),
      types 1 and 6 (7%) and type 3 (4%). The serotype 5 specimens showed 85% and 90%
      reactivity with recombinant antigens c100-3 and c22-3c, respectively; serotype 1
      specimens showed 75% and 100% reactivity with these antigens. All serotype 5
      specimens reacted with the c33-c antigen, but only 60% of serotype 1 specimens
      reacted with this antigen. The differences in the reactivity of the serotype 5
      and serotype 1 specimens for c33-c antigen in the RIBA were significant, but no
      significant differences in reactivity for antigens c-1-1, c100-3, and c22-3 were
      noted. Serotype 3 specimens showed equal reactivity with all four antigens used
      in the RIBA. CONCLUSION: The serotyping EIA was easy to use, rapid, and cost
      effective compared with molecular assays. This assay seems to be ideal for the
      routine diagnostic laboratory setting, but could not be used for certain clinical
      specimens. The demonstration of serotypes 5, 1, and 3 was not unexpected in this
      cohort. The occurrence of serotype 6, although concurrent and more likely to be a
      false cross reaction with serotype 1 peptides, requires confirmation by molecular
      genotyping before it can be claimed that this type is present in South Africa.

PMID- 9038738
TI  - Histological features predictive of liver fibrosis in chronic hepatitis C
      infection.
AB  - AIMS: To assess which pathological features are associated with a sensitive
      marker of liver fibrogenesis and thus of the potential development of fibrosis in
      hepatitis C. METHODS: The degree of liver fibrogenesis was evaluated by
      quantification of type I collagen mRNA and transforming growth factor (TGF) beta
      1 mRNA (a major profibrogenic cytokine) in liver biopsy specimens from 28
      patients with chronic hepatitis C and five controls, using a quantitative reverse
      transcription polymerase chain reaction (RT-PCR) assay. Results of mRNA
      quantification were correlated with histological lesions scored
      semiquantitatively in the same specimens. RESULTS: Type I collagen mRNA was more
      strongly expressed in patients than in controls and correlated with the degree of
      fibrosis, but not with any of the necro-inflammatory lesions (portal
      inflammation, piecemeal necrosis, and lobular necrosis). TGF beta 1 mRNA
      concentration was higher in patients than in controls and correlated with
      histological grade of activity and lobular necrosis. This result was confirmed by
      in situ hybridisation experiments which showed that TGF beta 1 mRNA was mainly
      expressed in areas of focal lobular necrosis in chronic hepatitis C. CONCLUSION:
      This study shows that fibrosis, rather than necro-inflammatory lesions or
      activity scores, is associated with fibrogenesis and thus with potential
      aggravation of the fibrous deposit in chronic hepatitis C. Lobular necrosis is an
      important predictor of prognosis in chronic hepatitis C, as shown by its strong
      association with TGF beta 1 mRNA expression.

PMID- 9038739
TI  - Association between Helicobacter pylori infection and serum pepsinogen
      concentrations in gastroduodenal disease.
AB  - AIM: To investigate the association between Helicobacter pylori infection and
      serum pepsinogen (PG) 1 and 2 concentrations in various gastroduodenal diseases.
      METHODS: Serum PG1 and 2 concentrations and antibodies to H pylori were measured
      by enzyme linked immunosorbent assay (ELISA); gastric mucosal pH was assessed and
      urease activity in biopsy tissue was determined. A comparison of the ELISA and
      urease test results permitted division of the cases into positive, false
      positive, false negative and negative categories for control, gastritis, and
      ulcer groups. RESULTS: The gastric mucosal pH and serum PG2 in cases positive for
      H pylori were significantly increased in ulcer and gastritis cases compared with
      H pylori negative cases. Similar tendencies were observed for the false positive
      and false negative categories. CONCLUSIONS: A positive ELISA reaction for
      antibodies and an increased serum PG2 concentration are reliable indicators of H
      pylori infection.

PMID- 9038740
TI  - Adenocarcinoma of the anal glands.
AB  - Adenocarcinoma of the anal glands is very rare but it is an important lesion to
      recognise as with early diagnosis, it has an excellent prognosis. Because it
      involves the submucosa widely and penetrates the mucosa late, it can be mistaken
      for metastatic gastrointestinal carcinoma, or tumour arising in sinuses and
      fistulae. Two cases, in a 44 year old man and a 73 year old woman, which
      illustrate the typical features are reported, in one of which the diagnosis was
      missed originally. In situ neoplastic change of the associated anal glands and
      secretion of mucin lacking O-acetyl groups are useful pointers.

PMID- 9038741
TI  - Leukaemia of natural killer cell large granular lymphocyte type with HLA-DR-CD16
      CD56bright+ phenotype.
AB  - The case is reported of a 45 year old woman with the rare leukaemia of natural
      killer cell large granular lymphocyte (NK/ LGL) type. Cytometric analysis of
      leukaemic blasts showed that they were positive for CD2, CD38, and CD56 antigens
      but negative for a series of antigens including CD3, CD7, CD16, and HLA-DR.
      Rearrangements of the beta T cell receptor, and heavy and kappa immunoglobulin
      genes were not detected and neither were chromosomal abnormalities. Leukaemic
      blasts developed NK cytotoxicity. The patient failed to respond to aggressive
      chemotherapy and died three months after diagnosis. The lack of expression of HLA
      DR is an extraordinary characteristic of this case, as all cases of acute NK cell
      leukaemias described to date expressed HLA-DR. The immunophenotype observed in
      the NK cell leukaemic blasts may represent the counterpart of a hypothetical
      normal cell precursor in an early stage of ontogenic NK cell development.

PMID- 9038742
TI  - Presence of the bcr/abl rearrangement in a patient with chronic neutrophilic
      leukaemia.
AB  - An 83 year old women presented with a myeloproliferative disorder involving the
      myeloid and megakaryocytic lines, and characterised by mature neutrophil
      leucocytosis. There was a high/normal neutrophil alkaline phosphatase activity
      and absence of the Philadelphia chromosome, features compatible with a diagnosis
      of chronic neutrophilic leukaemia (CNL). Southern blot analysis of the patient's
      DNA revealed the presence of the bcr/abl rearrangement. Combined with a previous
      report of detection of Ph1 chromosome in long term bone marrow cultures in a
      patient with CNL, this finding suggests that the bcr/abl hybrid gene might
      occasionally result in a myeloproliferative disorder with a phenotype closely
      resembling that of CNL.

PMID- 9038744
TI  - Helicobacter pylori antibody titres in serum, plasma and successively thawed
      specimens: implications for epidemiological and clinical studies.
AB  - Agreement between Helicobacter pylori IgG antibodies measured using the Pylori
      set EIA-G kit in serum, plasma and successively thawed specimens was studied and
      the implications for epidemiological and clinical studies assessed. Plasma titres
      may differ from serum titres by -6% to +8% and therefore may be substituted for
      serum. The change in titre around the cut off value was -0.31 (se = 5.7, p =
      0.96) per thaw. The estimated maximum drop after three thawings, 34.5, would
      result in only a small decrease in sensitivity (1.3%). For qualitative
      epidemiological studies, this additional misclassification rate is relatively
      small. However, positive titres did reduce over successive thawings, with the
      estimated maximum drop being 11.4% per thaw. Therefore, thawing does need to be
      considered as a contributing factor when interpreting titre drops in eradication
      trials. Baseline and follow up specimens from clinical studies should be thawed
      once only and tested concurrently.

PMID- 9038743
TI  - Myxoid renal cell carcinoma: histological, immunocytochemical and ultrastructural
      study.
AB  - Renal cell carcinomas show a variety of histological features. A case of a renal
      tumour arising in a 44 year old African man is reported. The tumour was composed
      of a cobweb-like pattern of narrow anastomising tubules lined by cuboidal cells
      separated by a hypocellular myxoid stroma. Immunohistochemical stains were
      consistent with a renal cell origin. The differential diagnosis in these cases
      includes sarcoma.

PMID- 9038745
TI  - The order of draw of blood specimens into additive containing tubes not affect
      potassium and calcium measurements.
AB  - The effect of order of draw when taking blood into tubes containing additive was
      investigated in 47 medical inpatients; 12 of these patients acted as a control
      group. The samples were analysed in the order in which they were withdrawn. The
      results of potassium and calcium concentrations did not differ significantly
      between groups. Manufacturers recommend a specific order of draw when taking
      blood using vacuum based blood collection systems, which are routinely used in
      many hospitals. The results of this study, however, show that order of draw has
      no effect on calcium or potassium concentrations.

PMID- 9038746
TI  - Hodgkin's disease and common variable immunodeficiency.

PMID- 9038747
TI  - Frequency of coincident iron deficiency and beta-thalassaemia trait.

PMID- 9038748
TI  - Contraction band necrosis.

PMID- 9038749
TI  - Divergent differentiation in soft tissue sarcomas.

PMID- 9038750
TI  - The coroner's necropsy--an epidemiological treasure trove.

PMID- 9038751
TI  - Resistant enterococci--mechanisms, laboratory detection and control in hospitals.

PMID- 9038752
TI  - ACP Broadsheet No 149: September 1996. Serological diagnosis of gluten sensitive
      enteropathy.

PMID- 9038753
TI  - Simple detection of the 5S ribosomal RNA of Pneumocystis carinii using in situ
      hybridisation.
AB  - AIMS: To investigate the effectiveness of digoxigenin incorporated double
      stranded DNA probes produced by the polymerase chain reaction (PCR), for the
      detection of Pneumocystis carinii, using in situ hybridisation (ISH). METHODS:
      Formalin fixed, paraffin wax embedded sections of 26 human lung samples from 11
      patients with P carinii pneumonia (PCP), and 15 with various types of fungal and
      viral pneumonia, were obtained during necropsy or transbronchial lung biopsy.
      Three additional PCP induced rat lung samples were also tested. PCR probes were
      prepared using the digoxigenin labelling mixture, and they were amplified from
      the DNA of a PCP induced rat lung after administration of dexamethasone, on the
      basis that 5S ribosomal RNA sequences are identical in human and rat P carinii.
      ISH was performed using this probe, and visualised using the digoxigenin nucleic
      acid detection kit. An immunohistochemical study using anti-human Pneumocystis
      monoclonal antibody was also carried out in parallel. RESULTS: ISH positively
      stained eight (of eight) lung necropsy specimens from patients with PCP, three
      (of three) transbronchial lung biopsy specimens from patients with PCP, and none
      of the three PCP induced rat lung specimens. In contrast, none of the specimens
      from patients with pneumonia caused by Aspergillus sp (n = 5), Candida sp (n =
      4), Cryptococcus sp (n = 2), mucormycosis (n = 2), or cytomegalovirus (n = 2)
      were positive on ISH or immunohistochemistry. CONCLUSIONS: Using a digoxigenin
      labelled PCR probe for the entire 5S rRNA sequence in conjunction with
      conventional staining, ISH is highly reactive and specific for the diagnosis of
      PCP.

PMID- 9038754
TI  - Immunocytochemistry of mucosal changes in patients infected with the intestinal
      nematode Strongyloides stercoralis.
AB  - AIM: To investigate the immunopathological changes in duodenal tissues induced by
      strongyloidiasis and to relate these to degrees of clinical severity. METHODS:
      Tissues taken from 21 patients showing mild, moderate or severe symptoms of
      strongyloidiasis, and from non-infected controls, were sectioned and stained
      immunocytochemically for IgA, secretory component (SC) and HLA-DR.
      Immunopathology was assessed by changes in numbers, intensity and distribution of
      stained cells. RESULTS: Parasitised individuals showed villous atrophy and crypt
      hyperplasia. There was notable infiltration of the lamina propria by IgA positive
      plasma cells and of the epithelium by intraepithelial lymphocytes. Infection was
      also associated with increased expression of SC and decreased expression of HLA
      DR in epithelial cells. Changes in all parameters correlated with degree of
      clinical severity. CONCLUSIONS: Profound mucosal changes are induced by
      strongyloidiasis. Some are analogous to those seen in coeliac disease, but others
      seem quite unusual. It is likely that these changes are functionally related to
      the immunopathophysiological consequences of infection seen in patients with
      severe disease.

PMID- 9038756
TI  - Immunohistological analysis of tumour growth factor beta 1 expression in normal
      and inflamed salivary glands.
AB  - AIM: To determine whether transforming growth factor-beta 1 (TGF-beta 1) has a
      pathogenetic role in disease of the salivary glands. METHODS: An indirect
      immunohistochemical technique was used to analyse TGF-beta 1 expression in six
      specimens of normal salivary gland and 23 surgical specimens. RESULTS: TGF-beta 1
      was strongly expressed in the ductal epithelial cells of normal salivary gland
      tissues (six of six cases) and in inflammatory conditions (eight of 11 cases). In
      contrast, TGF-beta 1 was not detectable in ductal epithelial cells expressing HLA
      DR around infiltrating CD4+ CD45RO+ activated T cells, in the salivary gland
      tissue of patients with Sjogren's syndrome. CONCLUSION: Because TGF-beta 1 has an
      essential role in the mucosal immunity of salivary glands, abnormal expression of
      this cytokine must be regarded as a candidate in the pathogenesis of Sjogren's
      syndrome.

PMID- 9038755
TI  - Differential regulation of leucocyte L-selectin (CD62L) expression in normal
      lymphoid and inflamed extralymphoid tissues.
AB  - AIMS: To study tissue expression of L-selectin, a leucocyte cell surface molecule
      that is considered to be involved in adhesion to certain endothelia, particularly
      in peripheral lymph nodes and during inflammation, and is shed upon leucocyte
      activation. METHODS: Leucocytes were examined by immunohistochemistry and double
      immunofluorescence staining in various lymphoid sites and normal and inflamed
      extralymphoid tissues. RESULTS: L-selectin was present on mantle zone B
      lymphocytes in different lymphoid sites, including in intestinal lymphoid tissue,
      but was absent on germinal centre B cells. Splenic white pulp B cells also
      expressed L-selectin. The proportion of T lymphocytes expressing L-selectin
      depended on the site under study, being greatest in peripheral lymph nodes (mean
      48% of T cells positive), and lower in mucosal lymphoid sites and spleen (9 and
      11% positive, respectively). Non-lymphocytic L-selectin staining was observed on
      follicular dendritic cells in tonsils and on macrophages in thymus. L-selectin
      positive leucocytes were rare in normal extralymphoid tissues, and relatively few
      were seen in most inflammatory settings. However, in rejecting renal transplants,
      a higher proportion (30%) of leucocytes expressed L-selectin. CONCLUSIONS:
      Overall, the results indicate how the degree of L-selectin expression by
      leucocytes in particular tissues may reflect a requirement for L-selectin
      expression for entry into those tissues and the activation state of leucocytes
      once localised there.

PMID- 9038757
TI  - Expression of the alpha 5 beta 1 fibronectin receptor on T lymphocytes of
      patients with HIV-1 infection.
AB  - AIMS: To evaluate the expression of the alpha 5 beta 1 integrin fibronectin
      receptor (FNR), which mediates several processes, including phagocytosis, cell
      motility and the immune response, on T lymphocytes of patients with HIV-1
      infection. METHODS: T lymphocytes were incubated with monoclonal antibody
      directed against FNR and then with monoclonal antibodies, conjugated with
      phycoerythrin, directed against CD3, CD4 and CD8 positive cells. Expression of
      FNR on CD3, CD4 and CD8 positive cells was analysed using flow cytometry.
      RESULTS: Normal expression of FNR was observed on CD3 positive cells from
      asymptomatic HIV positive patients and those with AIDS. Increased expression of
      FNR was observed on CD8 positive cells from asymptomatic HIV positive patients
      and on CD4 positive cells from patients with AIDS. Increased FNR expression was
      observed on CD4 positive cells from patients with AIDS, particularly those with
      opportunistic infections caused by Pneumocystis carinii, Mycobacterium sp,
      Toxoplasma gondii, and Cryptococcus neoformans. CONCLUSION: Increased expression
      of FNR on CD8 and CD4 positive cells in asymptomatic HIV positive patients and
      those with AIDS, respectively, may be an epiphenomenon correlated with lymphocyte
      activation by HIV-1 or opportunistic infection, Further study is required to
      determine whether upregulation of FNR expression has a direct role in the
      pathogenesis of AIDS.

PMID- 9038758
TI  - The coroner's necropsy in sudden death: an under-used source of epidemiological
      information.
AB  - AIMS: To determine the number of unsuspected disease processes found in a series
      of cases of sudden unexpected death occurring outside hospital and to enumerate
      how many of these were not recorded on the death certificate. METHODS: In a
      series of 1000 routine coroners' necropsies for sudden unexpected death, major
      findings that had not been known about in life were recorded. Macroscopic
      findings were confirmed histologically as appropriate. The deaths occurred either
      outside hospital or in the Accident and Emergency department before the patient
      could be examined. Cot deaths and decomposed bodies were excluded. RESULTS: There
      were 575 major findings in 532 (53.2%) subjects that had been clinically silent
      in life. Of these 575 findings, 277 (48.2%) were not the cause of death and so
      did not appear on the death certificate. Eighty per cent of the major alimentary
      system findings and all of the genitourinary findings were of this type. In
      addition, however, 30% of the major cardiovascular and 34% of the major
      respiratory findings were not recorded on the death certificate for this reason.
      CONCLUSIONS: A large amount of important epidemiological data is being lost in
      the operation of the coronial system. Some of this information is irrecoverable
      as the function of the death certificate is to provide a cause of death only. In
      addition, information may be being lost because the necropsy is not being
      performed adequately and is not subject to audit.

PMID- 9038759
TI  - Ki-67 expression in early prostate cancer and associated pathological lesions.
AB  - AIM: To assess cell proliferation in early prostate cancer and associated
      pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation
      index was measured in early stage prostatic carcinoma in 37 incidental tumours
      diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers
      treated by radical prostatectomy. Proliferation indexes have also been measured
      in areas of normal peripheral zone, transition zone hyperplasia, atrophic
      appearing lobules, and high grade prostatic intraepithelial neoplasia in the
      radical prostatectomy cases. RESULTS: In the TURP series the proliferation index
      correlated with grade and stage. Logistic regression analysis, however, showed
      that Gleason grade was the most reliable predictor of biopsy proven residual
      disease and clinical progression. In the radical series transition zone carcinoma
      the proliferation index was half that of peripheral zone carcinoma. The atrophic
      lobules also showed a high proliferation index of the same order as seen in the
      peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation
      index and in hyperplastic transition zone it was also less than the other areas.
      CONCLUSIONS: There is only limited support for the correlation of proliferation
      index with grade in early stage prostatic carcinoma. The findings do not suggest
      that proliferation index adds to the prognostic information given by grade and
      stage in pT1 disease. The significant difference in proliferation index in
      transition zone and peripheral zone carcinomas supports the morphological
      distinction of these tumour types and is consistent with differences in
      biological behaviour. The high proliferation index in lobules considered
      morphologically atrophic is reminiscent of previous observations in which
      carcinoma was spatially associated with atrophy.

PMID- 9038760
TI  - Immunoglobulin light chain mRNA detected by in situ hybridisation in diagnostic
      fine needle aspiration cytology specimens.
AB  - AIMS: To demonstrate expression of immunoglobulin light chain mRNA in diagnostic
      fine needle aspiration (FNA) cytology specimens using an in situ hybridisation
      (ISH) technique; and to evaluate ISH in a series of reactive lymphoid
      proliferations and malignant lymphomas. METHODS: Forty diagnostic FNA specimens
      showing a lymphoid cell population were examined for immunoglobulin light chain
      mRNA expression using ISH. Aspirates were obtained from lymph node (n = 34),
      salivary gland (n = 3), subcutaneous tissue, thyroid and breast (n = 1 each). The
      cases included 20 B cell lymphomas, five cases of Hodgkin's disease and 15
      reactive lymphoid proliferations. Comparison with light chain immunoreactivity
      was made in 36 cases and histological correlation from biopsy material was
      available in 24. RESULTS: Immunoglobulin light chain restriction was demonstrated
      in 14 of 20 B cell lymphomas using ISH and in six of 17 B cell lymphomas using
      immunocytochemistry. A polytypic pattern of light chain expression was observed
      in four of five cases of Hodgkin's disease with both techniques, and in 12 of 15
      and 11 of 14 reactive lymphoid proliferations using ISH and immunocytochemistry,
      respectively. CONCLUSIONS: The assessment of immunoglobulin light chain
      expression is a useful adjunct to morphology in the diagnosis of reactive and
      malignant lymphoid proliferations in FNA specimens. Light chain restriction can
      be shown using either immunocytochemistry or ISH, but the latter is more
      sensitive in the diagnosis of B cell lymphoma.

PMID- 9038761
TI  - Limited value of serum holo-transcobalamin II measurements in the differential
      diagnosis of macrocytosis.
AB  - AIM: To study the value of serum holo-transcobalamin II (holo-TCII) measurements
      in the differential diagnosis of macrocytosis. METHODS: Holo-TCII concentrations
      were measured in serum samples from 50 healthy non-vegetarian subjects and 30
      patients with macrocytosis, using a technique based on the adsorption of holo
      TCII with amorphous, precipitated silica. Deoxyuridine (dU) suppression tests
      were performed on the bone marrow cells of all the patients. Haematological
      diagnoses were made using standard criteria. RESULTS: The causes of macrocytosis
      were cobalamin (Cbl) deficiency due to pernicious anaemia or following partial
      gastrectomy (10 patients), dietary folate deficiency with/without Cb1 deficiency
      (four patients), chronic alcoholism (four patients), myelodysplastic syndrome
      (five patients), treatment with methotrexate or azathioprine (three patients),
      and congenital dyserythropoietic anaemia (CDA) (four patients). Undetectable or
      low holo-TCII concentrations were found in all patients with Cb1 deficiency and
      in some or all patients from each of the other diagnostic categories. There was
      also no correlation between the dU suppressed value and the holo-TCII
      concentration: all 15 patients with high dU suppressed values and nine of 15 with
      normal dU suppressed values, including four patients with CDA, had low holo-TCII
      concentrations. CONCLUSIONS: Measurements of serum holo-TCII concentrations by
      the silica adsorption method are not of value in the differential diagnosis of
      macrocytosis. The finding of low serum holo-TCII concentrations in patients with
      macrocytosis due to causes other than Cb1 deficiency may result not only from a
      state of negative Cb1 balance but also from other factors, such as increased
      utilisation of holo-TCII as a consequence of erythroid hyperplasia.

PMID- 9038762
TI  - Limitations of paperless on-line reporting of diagnostic bacteriology culture
      results.
AB  - AIMS: To estimate the extent to which microbiology laboratory results made
      available on a computerised reporting system do not reach their intended
      destination. METHODS: Prospective observational study of 180 urine cultures
      submitted from patients seen at the accident and emergency department of a 250
      bed university affiliated general hospital. Observations were made of: telephone
      requests for results; whether results were noted in patients' charts; and
      antibiotic administration to patients sent home. RESULTS: Results were
      requested/recorded for 73% of 37 patients admitted to hospital and for only 23%
      of 143 patients sent home (p < 1 x 10(-7)). Overall, results were more frequently
      recorded for patients with positive cultures (p = 0.04). When determined
      separately for admitted and discharged groups, this association was not shown.
      Three of 14 culture positive patients sent home and for whom results were not
      recorded received inappropriate therapy; 19 culture negative patients were given
      antibiotics. CONCLUSIONS: In view of the results, measures were instituted to
      ensure delivery of printed reports to the health care providers of patients not
      admitted from the accident and emergency department. Organisations operating
      computerised reporting systems in evolving health care settings must ensure that
      system design guarantees delivery of reports to all end-users. This will minimise
      therapeutic problems, reduce wastage of laboratory resources, and limit risks of
      litigation.

PMID- 9038764
TI  - Pontine neurocytoma.
AB  - A case of neurocytoma arising in the rostral pontine region of an 18 year old man
      is reported. The patient developed a right trochlear nerve palsy and was shown to
      have a well circumscribed, contrast enhancing mass on magnetic resonance imaging.
      The tumour was characterised histologically by a uniform population of medium
      sized round nuclei and slightly eosinophilic cytoplasm or occasional perinuclear
      halos, with delicate branching capillaries, patches of fibrillary matrix, and
      occasional perivascular pseudorosettes. Immunohistochemical studies demonstrated
      strong reactivity for synaptophysin in the fibrillary processes and cytoplasm of
      tumour cells. The present tumour is an exceptional case of neurocytoma arising in
      the pons.

PMID- 9038763
TI  - Granulocytic sarcoma with expression of CD30.
AB  - A case of a young man with a spinal epidural tumour, initially diagnosed as large
      cell anaplastic malignant lymphoma, is reported. The tumour consisted of poorly
      differentiated cells showing immunoreactivity with antibodies directed against
      CD30 and CD45. Ten months later the patient developed acute myeloid leukaemia.
      The histological slides of the epidural tumour were reviewed, including
      additional enzymochemical and immunochemical stains. As the tumour showed
      immunoreactivity for myeloperoxidase and chloroacetate esterase, it was
      reclassified as a granulocytic sarcoma.

PMID- 9038765
TI  - A case against the specificity of "cardiac" troponin-T.
AB  - A case of a spurious rise in cardiac troponin-T in an 85 year old Caucasian man
      with myelodysplastic syndrome and multiple malignancies but with intact cardiac
      and renal function is reported. The patient presented to the accident and
      emergency department with fever and chest pain. Inconsistent laboratory findings
      in biochemical markers diagnostic of myocardial infarction were observed.
      Discrepant findings included a rise in the concentration of the cardiac specific
      marker troponin-T in the absence of an increase in creatine kinase (CK) isoenzyme
      MB activity. Somewhat surprisingly, there was a significant and consistent
      increase in CK isoenzyme BB activity. Awareness of the increase in troponin-T
      concentrations in patients with multiple clinical non-cardiac problems may
      prevent an erroneous diagnosis of myocardial infarction and avert institution of
      unduly aggressive treatment.

PMID- 9038766
TI  - High temperature antigen retrieval and loss of nuclear morphology: a comparison
      of microwave and autoclave techniques.
AB  - The use of high temperature antigen retrieval methods has been of major
      importance in increasing the diagnostic utility of immunocytochemistry. However,
      these techniques are not without their problems and in this report attention is
      drawn to a loss of nuclear morphological detail, including mitotic figures,
      following microwave antigen retrieval. This was not seen with an equivalent
      autoclave technique. This phenomenon was quantified using image analysis in a
      group of B cell lymphomas stained with the antibody L26. Loss of nuclear
      morphological detail may lead to difficulty in identifying cells accurately,
      which is important in the diagnostic setting-for example, when trying to
      distinguish a malignant lymphoid infiltrate within a mixed cell population. In
      such cases it would clearly be wise to consider the use of alternative high
      temperature retrieval methods and accept their slightly lower staining
      enhancement capability compared with the microwave technique.

PMID- 9038767
TI  - Focal rhabdomyosarcomatous differentiation in primary liposarcoma.
AB  - A unique case of primary myxoid liposarcoma of the thigh, in which focal
      pleomorphic areas were present containing rhabdomyoblasts, is described. Focal
      rhabdomyosarcoma in liposarcoma has only rarely been reported previously and only
      in dedifferentiated liposarcomas of the retroperitoneum. All but one have been
      recurrences with rhabdomyoblasts being absent in the primary liposarcoma. As
      rhabdomyoblasts were only focally present, the present case is regarded as
      liposarcoma with focal divergent rhabdomyoblastic differentiation rather than
      malignant mesenchymoma.

PMID- 9038768
TI  - Pseudopyropoikilocytosis: a striking artefact.
AB  - The blood films both of patients with hereditary pyropoikilocytosis and of those
      with severe thermal burns are characterised by budding erythrocytes and the
      presence of microspherocytes. Recently, a fourth example of similar morphological
      features, caused by overheating of a blood specimen in a motor vehicle during
      transport to the laboratory, has been observed. It is important to be aware of
      this artefact as failure to recognise it is likely to lead to diagnostic
      confusion and unnecessary further testing, causing inconvenience to the patient.

PMID- 9038769
TI  - Fatal bone marrow embolism in a patient with sickle cell beta + thalassaemia.
AB  - Sickle cell beta + thalassaemia is regarded as the mildest of the sickle cell
      haemoglobinopathy syndromes with a benign natural course. In contrast to sickle
      cell disease, severe life threatening complications are not usually associated
      with this genotype. A case of a 30 year old West Indian man who, previously
      asymptomatic for 10 years, sustained a fatal pulmonary bone marrow embolism, is
      reported. This case report illustrates that serious, even fatal, complications
      may occur in patients with this 'benign' condition and bone marrow embolism
      should be included in the differential diagnosis of acute crisis in these
      patients.

PMID- 9038771
TI  - Review of clinical activity by microbiologists.

PMID- 9038770
TI  - Simple method for necropsy dissection of the abdominal organs after abdominal
      surgery.
AB  - This paper illustrates a simple method of necropsy dissection of the abdominal
      organs after abdominal surgery. The organs are removed in one block as per the
      method described by Letulle. A retroperitoneal approach is then used. Structures
      are dissected away in a series of layers using the vasculature for guidance. This
      technique permits the examination of important structures in the postoperative
      abdomen which would otherwise be extremely difficult and time consuming using
      conventional methods. The anatomy is demonstrated without being obscured by the
      contents of the peritoneal cavity.

PMID- 9038772
TI  - Prolongation of duration of ovulation in ageing mice.
AB  - In female mice, fertility and fecundity decrease progressively with ageing for
      unknown reasons. The time of day at which ovulation occurred and the time
      required for all the follicles to ovulate in young (10-14 weeks), middle-aged (9
      11 months) and old (13-15 months) female mice were compared under controlled
      lighting conditions (12 h dark to 12 h light) to determine the relationship
      between maternal age and reproductive loss. The number of oocytes present in the
      follicles and the ampullae were counted at intervals of 1 h after mating. In the
      groups of young and middle-aged mice, the percentage of oocytes ovulated into the
      ampullae increased gradually and reached almost 100% at 7 h after the midpoint of
      the dark period. Whereas, in the group of old mice, it took twice as long (15 h)
      to reach 100%. However, the mean number of total oocytes remained relatively
      unchanged (young, 14.8: middle-aged, 16.2; old, 13.8). The prolongation in the
      time required for all the follicles to ovulate in old female mice may therefore
      be associated with a low fertilization rate and consequently the age-related
      decrease in number of offspring produced.

PMID- 9038773
TI  - Blood plasma concentrations of progesterone, sperm storage and sperm viability
      and fertility in Gould's wattled bat (Chalinolobus gouldii).
AB  - The fertility and viability of spermatozoa stored by male and female Gould's
      wattled bats, Chalinolobus gouldii, was investigated in a captive colony of ten
      bats (three males and seven females). Bats were housed in outdoor flight cages.
      Plasma progesterone concentrations, measured using double antibody
      radioimmunoassay, isolation experiments plus sperm motility and sperm membrane
      stability tests were used to evaluate the viability and fertility of stored
      spermatozoa. Mean plasma progesterone concentrations were lowest during midwinter
      (< 0.5 ng ml-1) with a 20-fold increase recorded in late winter to early spring.
      During pregnancy, plasma progesterone concentrations increased to about 13 ng ml
      1 and returned to basal values soon after parturition. The results of the plasma
      progesterone assays and the isolation experiments indicate that female C. gouldii
      can store fertile spermatozoa for at least 33 days. The investigation of
      spermatozoa stored by male C. gouldii revealed that 6-7 months after peak
      spermatogenesis about 60% of the stored spermatozoa were motile and more than 60%
      had stable membranes, indicating that the spermatozoa stored by males were viable
      and likely to be fertile. The results of this study clearly indicate that both
      male and female C. gouldii are capable of storing fertile spermatozoa for
      prolonged periods.

PMID- 9038774
TI  - Two modifiers of sperm transport within the fallopian tube of the rat.
AB  - In several mammals studied, ovulation appears to stimulate coordinated
      translocation of a few potential fertilizing spermatozoa to the ampulla from the
      caudal isthmus of the Fallopian tube. The present experiments demonstrate that,
      in the rat, this movement is regulated to a considerable degree within each duct
      by the ipsilateral ovary. Unilateral ovariectomy had no effect on ipsilateral
      sperm transport into the uterus, but this brought a unilateral quenching of sperm
      transport to the ampulla of the oviduct, from which spermatozoa were often
      totally or almost absent. This suppression was always complete on the ipsilateral
      side in unilaterally ovariectomized females anaesthetized with sodium
      pentobarbital soon after ovulation, and was evident bilaterally also at a highly
      significant level among intact females that were anaesthetized in this way.
      Unilateral ovariectomy and sodium barbital anaesthesia could provide experimental
      situations through which to decipher the mechanisms of normal sperm transport in
      the Fallopian tube.

PMID- 9038775
TI  - Partial purification from bovine follicular fluid of a factor of low molecular
      mass with inhibitory effects on the proliferation of bovine granulosa cells in
      vitro and on rat follicular development in vivo.
AB  - Bovine follicular fluid was aspirated from follicles of 2-20 mm in diameter,
      charcoal-treated to remove steroids and then separated into low and high
      molecular mass fractions. The low molecular mass (< 10 kDa) fraction was purified
      on a Sephadex G-25 chromatography column with formic acid as the eluent. Seven
      peaks were isolated and assayed for biological activity in cultures of bovine
      granulosa cells at concentrations of 10, 100 and 1000 ng ml-1. One peak (peak 4)
      inhibited (P < 0.001) the proliferation of granulosa cells when measured by cell
      counting and by [3H]thymidine incorporation (33-37% inhibition). This peak
      inhibited proliferation of granulosa cells from both small (< 2 mm) and medium (2
      10 mm) follicles, but not large (> 10 mm) follicles. The inhibitory effect of
      peak 4 was not due to a toxic effect on cells. Administration of peak 4 to rats
      did not affect liver or kidney masses but did decrease uterine (25%, P < 0.01)
      and ovarian (35%, P < 0.01) masses. Peak 4 also caused a reduction in the number
      of large follicles (65%, P < 0.01) but increased the number of small follicles
      (55%, P < 0.01). We have named the inhibitory factor associated with peak 4,
      granulosa cell-inhibitory factor (GCIF). The results presented suggest that GCIF
      may be a factor secreted by dominant follicles that inhibits the development of
      subordinate follicles.

PMID- 9038776
TI  - Modulation of the effects of FSH, androstenedione, epidermal growth factor (EGF)
      and insulin-like growth factor I (IGF-I) on bovine granulosa cells by GCIF, a
      growth-inhibitory factor of low molecular mass from bovine follicular fluid.
AB  - A granulosa cell-inhibitory factor (GCIF) of low molecular mass from bovine
      follicular fluid inhibits the proliferation of bovine granulosa cells in vitro
      and the growth of large follicles in rats in vivo. The present study examined the
      ability of GCIF to modulate the effects of FSH, epidermal growth factor (EGF),
      insulin-like growth factor I (IGF-I) and androstenedione on the proliferation of
      bovine granulosa cells and on aromatase activity in vitro. Granulosa cell
      proliferation was assayed by counting haemocytometric cells and by measuring the
      incorporation of [3H]thymidine into acid-precipitable material. Assay of
      aromatase activity was based on the conversion of [3H]androstenedione to [3H]H2O.
      FSH, androstenedione, EGF and IGF-I all stimulated (P < 0.01) granulosa cell
      proliferation; however, the addition of GCIF reduced (P < 0.01) cell
      proliferation in their presence. In the case of EGF, the addition of GCIF almost
      abolished the stimulatory response. FSH and IGF-I, but not EGF, stimulated (P <
      0.01) aromatase activity of granulosa cells. The stimulatory effect of IGF-I was
      decreased by GCIF. The inhibitory effects of GCIF indicate that it may play a
      significant role in regulating the effects of intraovarian growth factors on
      granulosa cells and the growth of follicles.

PMID- 9038777
TI  - Effect of homologous and heterologous seminal plasma on the fertilizing ability
      of ejaculated bull spermatozoa assessed by penetration of zona-free bovine
      oocytes.
AB  - The ability of seminal plasma to influence the fertility of ejaculated bull
      spermatozoa was examined using a sperm penetration assay for zona-free bovine
      oocytes. Washed, ejaculated spermatozoa from bulls of below (low) or above
      average (high) fertility were mixed with seminal plasma from the same bull, or
      with seminal plasma from a bull of contrasting fertility. Treated spermatozoa
      were stained with different fluorochromes and competed to penetrate oocytes after
      heterospermic insemination in vitro. Washed spermatozoa exposed to seminal plasma
      from bulls of high fertility penetrated more oocytes than those spermatozoa mixed
      with seminal plasma from bulls of low fertility (P < 0.01). Mixing low fertility
      spermatozoa with high fertility seminal plasma generally improved penetrating
      ability compared with low fertility spermatozoa mixed with low fertility seminal
      plasma (P = 0.05). Washed spermatozoa from a bull of low fertility mixed with his
      own seminal plasma had greater ability to penetrate oocytes than did washed
      spermatozoa from a bull of high fertility mixed with seminal plasma from a bull
      of low fertility (P < 0.01). The bias associated with using low fertility seminal
      plasma from the bull providing the spermatozoa was removed by repeating this
      experiment using pooled seminal plasma from different subfertile bulls. After
      combination with pooled seminal plasma from bulls of low fertility spermatozoa
      from bulls of high or low fertility penetrated oocytes in a similar way, but high
      fertility spermatozoa had a slightly higher penetration rate (P = 0.12). In
      conclusion, the penetration of zona-free oocytes by ejaculated spermatozoa from
      bulls of low fertility was marginally improved by seminal plasma from bulls of
      high fertility, but penetration by high fertility spermaotoza was decreased by
      exposure to low fertility seminal plasma. Seminal plasma from bulls of low
      fertility similarly affected the penetrating ability of high and low fertility
      spermatozoa if the seminal plasma used was foreign to the spermatozoa being
      tested.

PMID- 9038778
TI  - Dissociation of spontaneous testicular recrudescence and photorefractoriness in
      the Syrian hamster.
AB  - In male Syrian hamsters, short days induce regression of the reproductive system,
      but eventually spontaneous recrudescence occurs ensuing from refractoriness to
      the inhibitory photoperiod. Although the photoperiod of 12 L:12 D (12 h light:12
      h dark) may act like a short day by inducing the testicular cycle outlined above,
      it may fail to evoke the increase of circulating concentrations of prolactin that
      accompanies testicular recrudescence. This photoperiod may fail to induce
      photorefractoriness, as indicated by the prolonged low concentrations of
      prolactin in the blood. Herein, hamsters were exposed to either 8 L:16 D or 12
      L:12 D from weaning and by 28 weeks exposure to either photoperiod, the hamsters
      had large testes following recrudescence from a photoperiod induced-regression).
      Transfer to 8 L:16 D from 12 L:12 D at 28 weeks resulted in a second testicular
      regression and recrudescence. In a second experiment, the testes of hamsters
      moved to 8 L:16 D from 12 L:12 D after 29 weeks exposure to the latter
      photoperiod similarly regressed and then regrew. Serum concentrations of
      prolactin decreased in these males after transfer to the shorter daylength but
      also decreased in hamsters kept under 12 L:12 D both groups were usually below
      those of hamsters moved to 14 L:10 D. These results show that exposure for 28 or
      29 weeks to 12 L:12 D was insufficient to induce photorefractoriness, despite the
      recrudescence of the testes following involution.

PMID- 9038779
TI  - Gonadotrope responsiveness in orchidectomized sheep: effect of duration of a
      simulated follicular phase.
AB  - The effect of duration of a simulated follicular phase on gonadotrope
      responsiveness was assessed in orchidectomized sheep (wethers). The oestrogenic
      and hypothalamic inputs characteristic of the ovine follicular phase were
      simulated by continuous infusion of oestradiol (5 micrograms h-1 in 10% (v/v)
      ethanol saline) and circhoral delivery of GnRH (200 ng per hourly pulse) for 0,
      6, 12, 24, 48 or 96 h (n = 6 wethers per group). Responsiveness increased (P <
      0.05) with increasing duration of simulated follicular phase. In a second
      experiment, responsiveness was assessed 96 h after initiation of infusion of
      oestradiol in wethers receiving hourly pulses of GnRH or saline. Concurrent
      administration of GnRH reduced (P < 0.05) the magnitude of the oestradiol-induced
      increase in gonadotrope responsiveness. In a companion study, anterior pituitary
      tissue was collected 96 h after the start of infusion of oestradiol and circhoral
      delivery of GnRH or saline. Pituitary stores of LH and tissue concentrations of
      GnRH receptor and mRNA encoding the GnRH receptor were increased (P < 0.05) by
      oestradiol infusion. The magnitude of these oestradiol-induced responses was not
      affected (P > 0.05) by concurrent GnRH treatment. Tissue concentrations of FSH
      and mRNA encoding the FSH beta subunit were decreased (P < 0.05) by oestradiol
      infusion. This suppressive effect of oestradiol was not reversed by GnRH. These
      results indicate that oestradiol stimulation, but not concurrent delivery of
      GnRH, is essential for full expression of surge-like secretion of LH. In
      addition, the oestradiol-induced increase in gonadotrope responsiveness during
      the simulated follicular phase is sustained throughout the period of oestradiol
      delivery.

PMID- 9038780
TI  - Changes in content of mRNA encoding oxytocin in the pig uterus during the
      oestrous cycle, pregnancy, at parturition and in lactational anoestrus.
AB  - The aim of this study was to show that the pig uterus synthesizes oxytocin. Uteri
      were obtained from 2-7 pigs at regular intervals during the oestrous cycle,
      throughout pregnancy, at parturition and in lactational anoestrus. Localization
      of mRNA encoding oxytocin was by in situ hybridization and oxytocin
      concentrations were measured by radioimmunoassay. As reproductive status changed,
      mRNA encoding oxytocin varied significantly (P < 0.05). Uterine tissue type was a
      significant factor in determining synthesis of mRNA encoding oxytocin (P <
      0.001). In luminal epithelia, concentrations of mRNA encoding oxytocin were
      greater at oestrus than during day 14 of the luteal phase (P < 0.01) or at any
      stage of pregnancy (P < 0.05), with concentrations minimal at parturition. This
      trend was also exhibited in uterine circular muscle. In longitudinal muscle,
      concentrations of mRNA encoding oxytocin were lower during late pregnancy than at
      oestrus (P < 0.05) or during the luteal phase (P < 0.05). Concentrations were
      minimal at parturition. The oxytocin content in endometrial and myometrial tissue
      was positively correlated across reproductive status (P < 0.02, r = 0.402, n =
      35). These data are the first indication that the uterine endometrium and
      musculature of the pig express mRNA encoding oxytocin. The luminal epithelium of
      animals at oestrus was particularly rich in mRNA encoding oxytocin, whilst late
      pregnant and parturient animals did not show a rise in mRNA encoding oxytocin.
      Local uterine synthesis of oxytocin may therefore be more important in control of
      the oestrous cycle than in pregnancy or at parturition in pigs.

PMID- 9038781
TI  - Rank and reproduction in the female spotted hyaena.
AB  - Female reproductive success varies with social rank in many gregarious mammals,
      including primates, ungulates and carnivores. Social groups of spotted hyaenas
      (Crocuta crocuta) are structured by hierarchical dominance relationships that
      determine individuals' priority of access to food and other resources. The
      influence of female social rank on several measures of reproductive success was
      examined in a population of free-living Crocuta in Kenya. The study population
      was continuously observed for seven years, making it possible to document litter
      sizes, interbirth intervals, ages of cubs at weaning, intervals between weaning
      one litter and conceiving the next, annual rates of production of cubs, and
      survival of offspring to reproductive maturity. The relationship between
      availability of food, social rank, and female fertility was examined by
      monitoring abundance of prey throughout the study period. Most measures of
      reproductive performance were strongly influenced by social rank. High-ranking
      females began breeding a younger ages, were more frequently able to support
      pregnancy and lactation concurrently experienced shorter intervals between
      litters, and produced more surviving offspring than did lower-ranking females.
      Low-ranking females exhibited better reproductive performance when prey animals
      were abundant than when prey were relatively scarce. By contrast, reproductive
      performance among high-ranking females was always superior to that exhibited by
      low-ranking females, and did not vary with prey abundance. Fertility among high
      ranking females thus appeared to be less vulnerable to fluctuations in the food
      supply than was that among low-ranking females.

PMID- 9038782
TI  - Immunolocalization of aromatase P-450 in ovarian tissue from pregnant and
      nonpregnant mares and in ovarian tumours.
AB  - Aromatase P-450 (P-450arom) is a crucial regulatory enzyme that is necessary for
      conversion of androgens to oestrogens. Corpora lutea and follicles were obtained
      from the ovaries of cyclic mares and from mares at day 20 and days 40-70 of
      pregnancy. The presence of P-450arom within specific cell types was investigated
      by immunostaining to determine potential sites of oestrogen synthesis.
      Immunoreactivity for P-450arom was confined to the granulosa layer of non-atretic
      follicles > 5 mm in diameter and to corpora lutea at all stages of the oestrous
      cycle and during pregnancy. These findings confirm that aromatization of
      androgens occurs within the granulosa cells of the preovulatory follicle of the
      mare and that the corpus luteum of the mare has the capacity for oestrogen
      production if adequate androgen substrate is available. Granulosa cells in
      ovarian tissue from three mares with granulosa cell tumours showed little
      staining for P-450arom which suggests that these tumours have little aromatizing
      capacity.

PMID- 9038783
TI  - Studies on [3H]palmitate-binding proteins of rat spermatozoa: a post
      translational modification of membrane proteins by fatty acid acylation.
AB  - The purpose of the present study was to demonstrate the post-translational
      modifications of sperm plasma membrane proteins by fatty acid acylation during
      sperm maturation in the epididymis. Rat epididymal spermatozoa were incubated at
      37 degrees C with various concentrations (100 microCi and 1 mCi) of [9
      10(n)3H]palmitic acid in a medium containing Tyrode's solution supplemented with
      sodium bicarbonate, sodium pyruvate and sodium lactate. The incorporation of
      [3H]palmitate in vitro was determined in epididymal spermatozoa and an attempt
      was made to identify the lipid-linked proteins of purified plasma membranes of
      maturing epididymal spermatozoa by autoradiography. The studies demonstrated that
      [3H]palmitate was covalently linked to a subset of membrane cytoskeleton proteins
      of maturing rat spermatozoa. The pattern of incorporation of lipid was a
      maturation-associated phenomenon as caput spermatozoa incorporated more
      radioactivity than did caudal spermatozoa. The labelled proteins appeared to be
      membrane-bound since 82% of radioactivity was associated with membrane fractions.
      Autoradiograms of SDS-PAGE gels of labelled caput sperm extract showed three
      prominent palmitate-incorporating protein bands of about 70, 56 and 36 kDa and
      few minor bands. Most of these proteins were present in the membrane fraction of
      caput spermatozoa. Labelled gels of both the sperm extracts and of purified
      membranes showed resistance to hydroxylamine treatment, suggesting that there are
      amide bonds between lipid and proteins. The higher incorporation of labelled
      palmitate by immature spermatozoa of the caput epididymis compared with mature
      spermatozoa from the cauda epididymis and the addition of palmitate to plasma
      membrane proteins of caput epididymal spermatozoa suggest that fatty acylation is
      a post-translational modification of sperm membrane proteins.

PMID- 9038784
TI  - Effects of the Booroola gene (FecB(B)) on bodymass, testis development and
      hormone concentrations during fetal life.
AB  - In female fetuses the Booroola gene (FecB(B)) is known to affect germ cell
      development and consequently the pattern of ovarian follicular growth during
      fetal and post-natal life. However in males, the role of this gene during fetal
      development is unknown. The aims of the study reported here were to examine the
      effects of the FecB(B) gene on development of male fetuses with respect to body
      and organ mass for example, pituitary gland, adrenal and mesonephros), testes
      development, including numbers of germ cells, and also the plasma concentrations
      or tissue contents of the reproductive hormones (FSH, LH and testosterone) at
      days 40, 55, 75, 90 and 135 of gestation. The FecB(B) gene was found to influence
      litter size, bodymass, crown-rump length and testis mass at most stages of
      gestation. Some effects were also noted on the mesonephros at days 40 and 55 and
      on the pituitary and adrenal at days 90 or 135 of gestation. However, the FecB(B)
      gene was not observed to have an effect on the patterns of germ cell development,
      on pituitary content or plasma concentrations of immunoreactive or bioactive FSH
      or immunoreactive LH or testicular content of testosterone. When embryo transfer
      experiments were performed to eliminate the effects of litter size at days 40, 90
      and 135 of gestation nearly all of the differences in bodymass, crown-rump length
      and organ mass disappeared. The only exception to this was at day 90 when
      bodymass continued to be lighter and crown-rump lengths smaller in the BB/B +
      fetuses compared with the +2 fetuses; the significance of this finding remains
      unknown. It is concluded that for Booroola male fetuses there are no direct
      effects of the FecB(B) gene on pituitary gonadotrophin function or testicular
      development after sexual differentiation. Moreover, although there may be
      temporal differences around day 90 of gestation, there are no long-term, direct
      effects of the FecB(B) gene on total body, adrenal, testis or pituitary mass.
      Collectively these findings for the male are similar to those for female fetuses
      except with regard to germ cell development.

PMID- 9038785
TI  - Transcription and cell cycle-dependent development of intranuclear bodies and
      granules in two-cell bovine embryos.
AB  - Bovine two-cell embryos were produced by maturation and fertilization in vitro
      and isolated at 27, 30 or 33 h after insemination. Embryos were incubated with
      [3H]uridine for 10 h. Other embryos were incubated with [3H]uridine for 1 h
      starting at 0-3 h, 3-6 h, 6-9 h or 9-12 h after cleavage (hpc) to the two-cell
      stage. Subsequently, all embryos were washed, fixed, dehydrated, embedded in Epon
      and sectioned for light microscope autoradiography and transmission electron
      microscopy. Thus, at the time of fixation the embryos incubated in [3H]uridine
      for 1 h represented the periods 1-4, 4-7, 7-10 and 10-13 hpc. Among embryos
      subjected to [3H]-uridine incubation for 10 h, a majority of those in interphase
      displayed auto-radiographic labelling over the nuclei, whereas none of the
      embryos incubated for 1 h did so. At 1-4 hpc, two-cell embryos presented electron
      dense nucleolus precursor bodies and large clusters of electron-dense granules of
      various sizes in their nuclei. At 4-7 hpc, ring-shaped or horseshoe-shaped bodies
      of the same electron density as the nucleolus precursor bodies were found in the
      periphery of the granule clusters. At 7-10 hpc, several incomplete ring-like
      bodies of the same electron density as the nucleus precursor bodies were found
      deeply embedded in the granule clusters. The interior of these bodies contained
      granules lining a central vacuole. At 10-13 hpc, all two-cell embryos were in
      mitosis. It is concluded that bovine embryos produced in vitro display a certain
      rate of transcription during the second cell cycle without the presence of a well
      defined transcriptional peak, and that this activity is paralleled by cell cycle
      dependent interaction of intranuclear bodies and granules.

PMID- 9038786
TI  - Relationships between FSH and ovarian follicular waves during the last six months
      of pregnancy in cattle.
AB  - Follicles were monitored daily by ultrasound and blood samples for FSH assay were
      collected daily from eight heifers from day 90 of pregnancy to the emergence of
      the first postpartum follicular wave. Follicles > or = 6 mm in diameter emerged
      in groups or waves in each heifer (P < 0.005). Follicular waves developed
      rhythmically throughout pregnancy, except that follicles > or = 6 mm were not
      detected during the last 21.6 +/- 2.4 (mean +/- SEM) days of pregnancy. The
      characteristics of the first follicular wave after day 90 were similar to
      previous reports for days 10-100. However, between months 4 (days 90-119) and 5,
      there was a decrease (P < 0.05) in monthly means for maximum diameter (mm) of
      largest (21.1 +/- 0.5 versus 9.5 +/- 0.5) and second largest (8.0 +/- 0.3 versus
      6.9 +/- 0.2) follicles, duration of the interwave interval (8.1 +/- 0.4 versus
      6.6 +/- 0.3 days), and number of follicles per wave (3.7 +/- 0.4 versus 2.5 +/-
      0.4). Averaged over all follicular waves during months 4-9, the concentrations of
      FSH normalized to the emergence of a follicular wave increased (P < 0.05) over
      the 3 days before emergence, reached peak values on the day of emergence of the
      future dominant follicle at 4 mm, and decreased (P < 0.05) over the 3 days
      following emergence. Surges in FSH concentrations occurred throughout pregnancy,
      but during the last 30 days of pregnancy the number of surges was reduced and
      each heifer had one or two ineffective surges (no follicular wave detected). The
      temporal relationship between FSH surges and emergence of waves was closer (P <
      0.01) than would be expected if the two events were independent. Surges of FSH
      occurred rhythmically even when there was no follicular response (no follicle > 5
      mm). In association with waves in which the largest follicle reached > or = 10 mm
      compared with 6-9 mm, there was greater depression in the FSH nadir, longer
      intervals from FSH peak to nadir, and longer intervals between adjacent FSH peaks
      and adjacent waves.

PMID- 9038787
TI  - Anti-mullerian hormone in relation to the growth and differentiation of the
      gubernacular primordia in mice.
AB  - The present study analysed gubernaculum development in mice that had been
      induced, through transgenesis, to express human anti-Mullerian hormone (h-AMH)
      throughout prenatal life. Growth and differentiation of the gubernacular
      primordia were assessed through the analysis of serial, transverse or sagittal,
      histological sections of the lower abdomen. Transgenic males and females
      expressed biologically active amounts of h-AMH as measured by sensitive and
      specific ELISA and evidenced through the regression, in females, of Mullerian
      ducts after day 13 of prenatal life. Gubernacular primordia became
      distinguishable at the same age in control and transgenic male and female fetuses
      on day 12 after coitus. In both groups gubernacular cords (inguinal folds of the
      genital mesenteries) increased in length more in females than in males while
      gubernacular cones showed larger growth in males. h-AMH thus appeared not to
      affect the sexually dimorphic pattern of growth and development of these
      structures. Growth and differentiation of the gubernacular primordia was further
      examined in 18-day-old control and h-AMH transgenic fetuses that had been exposed
      to testosterone propionate injected into their mothers on days 12 and 14 of
      pregnancy. Testosterone treatment affected, to a minor extent, the growth of the
      female gubernacular cords: these were reduced in length (but had a larger surface
      area) compared with controls. The gubernacular cones were slightly increased in
      length but male-like differentiation of the tissues of the cones into a muscular
      and mesenchymal component was not noticed to any extent. The observations thus
      add experimental support to the contention that AMH, even in combination with
      testosterone, is not effective in establishing the male pattern of gubernacular
      primordia development.

PMID- 9038789
TI  - Seasonal spermatogenesis and testosterone production in roe deer (Capreolus
      capreolus).
AB  - Quantitative changes in testes of roe deer were studied during the annual cycle.
      Testicular spermatozoa were counted and proportions of different cell types were
      estimated using DNA flow cytometry. A proliferation-specific antigen of somatic
      cells was evaluated by an immunoradiometric assay. Apoptosis was examined by cell
      death detection ELISA, and testosterone concentrations were measured with an
      enzymeimmunoassay. The testis mass of adults reached a maximum during the rut
      from mid-July to mid-August. Gonadal size corresponded to numbers of testicular
      spermatozoa g-1 testis. In the rutting period, epididymal spermatozoa were of the
      highest morphological and functional competence. The proportions of haploid (1c),
      diploid (2c) and tetraploid (4c) cells changed over time with the maximum of 1c
      cells during the breeding period. Meiotic division (1c:4c ratio) increased
      sharply immediately before rut, while mitosis (% cells in G2-M phase) was already
      high during spring. Proliferation and apoptosis revealed an opposite pattern
      during the annual cycle; the most intensive apoptosis occurred during the time of
      testis involution. Testosterone production showed a biphasic pattern. It dropped
      rapidly from the highest value in August to very low concentrations thereafter.
      Yearlings were characterized by smaller peaks of testicular growth and sperm
      production. Fawns started testicular growth and meiosis in winter. In conclusion,
      the production of spermatozoa in roe deer is intensified by enlargement of gonads
      as well as enhanced efficiency of spermatogenesis during the rut. Interrupted
      proliferation and stimulated apoptosis promote testis involution after the rut,
      and testosterone seems to play a role in the regulation of both processes.

PMID- 9038788
TI  - Expression of mRNA encoding decidualization-associated protein, a variant of
      acute-phase alpha 2 macroglobulin, by rat uterine tissues during pregnancy and
      pseudopregnancy.
AB  - The patterns of expression of mRNA encoding decidualization-associated protein
      (DAP) in the rat uterus from early, mid-, and late stages of pregnancy were
      examined by in situ hybridization to provide an insight into the function of DAP
      during pregnancy. Parallel studies were performed on rat uteri during the
      oestrous cycle and oil-induced deciduomata. DAP transcripts were absent in virgin
      uteri and during the day of implantation (day 5), low in early gestation tissues
      (days 8, 9) and high during midgestation (days 10-14). Expression of mRNA
      encoding DAP was first detected on day 8 of pregnancy in decidual cells of the
      lateral decidual glycogen wing areas. On day 9, mRNA encoding DAP was found in
      the same area as on day 8 as well as in the outer layer of cells in the
      antimesometrial decidua adjacent to the myometrium termed the fibrinoid capsula.
      On days 11 and 12, expression appeared in the decidual cells of the mesometrial
      decidua, and was particularly strong around the ectoplacental cone and blood
      vessels that were invaded by the trophoblast. By day 13 and throughout the
      remainder of pregnancy, expression occurred in the mesometrial decidua and
      metrial gland. No signal was observed in granulated metrial gland cells. mRNA
      encoding DAP was also found in the smooth circular muscle coat adjacent to the
      mesometrial decidua. A similar pattern and cellular localization of expression of
      mRNA encoding DAP expression was detected during the development of the
      deciduomata, artificially induced in the absence of a conceptus. The spatial and
      temporal patterns of expression correlated with a possible role for DAP in
      mediating fetal-maternal interactions and the establishment of the placental
      structure.

PMID- 9038790
TI  - Differential sensitivity of one-cell and two-cell rabbit embryos to sodium
      chloride and total osmolarity during culture into blastocysts.
AB  - One-cell or two-cell rabbit embryos were cultured in protein-free media with
      various NaCl concentrations and osmolarity to determine relative sensitivity of
      embryos to changes in media composition. Embryos from replicates of donor rabbits
      were distributed randomly across treatments and cultured at 39 degrees C. Zygotes
      were cultured in Expts 1, 2A and B, and 3, and two-cell embryos were cultured in
      Expts 4A and 4B. In Expt 1, blastocyst formation and number of cells were highest
      (P < 0.05) in the control medium with 93 mmol NaCl l-1 (270 mosmols) compared
      with media containing 63, and 116 mmol NaCl l-1 (220 and 316 mosmols). In Expt 2,
      embryos were cultured in media with 70 or 93 mmol NaCl l-1, varying in osmolarity
      from 250 to 320 mosmols by adding sorbitol. In media with 70 mmol NaCl l-1 and
      osmolarities of 250, 280 and 300 mosmols, there were 41, 56 and 50% expanded
      blastocysts, respectively (P < 0.05). With 93 mmol NaCl l-1 and osmolarities of
      270, 293 and 320 mosmols, embryos developed into 37.53 and 27% expanded
      blastocysts, respectively, (P < 0.05). In Expts 3A and 3B and 4A and 4B, the
      osmolarity of the medium was maintained at 270 mosmols by adding sorbito to media
      containing 40 or 60 mmol NaCl l-1, and other components were reduced in media
      containing 100 and 116 mmol NaCl l-1 to compensate for the higher NaCl. Zygote
      development into blastocysts was greatly suppressed (P < 0.05) in media with 40,
      60, 100 and 116 mm NaCl l-1, compared with the control (93 mmol NaCl l-1),
      whereas development of two-cell embryos into blastocysts was much less affected.
      These results appear to reflect a direct sodium chloride as well as osmolarity
      effect on embryo development; and zygotes are much more sensitive to these
      effects than are two-cell embryos.

PMID- 9038791
TI  - High molecular mass forms of epidermal growth factor in pig uterine secretions.
AB  - Accumulating evidence suggests that uterine luminal fluids contain a variety of
      polypeptide growth factors and cytokines that, it is speculated, have roles in
      the development, growth and differentiation of the uterus and, during pregnancy,
      in the growth and survival of the embryo. Although epidermal growth factor (EGF)
      has previously been identified by radioimmunoassay and immunohistochemistry in
      the pig uterus, there have been no detailed studies of the secreted EGF protein.
      EGF was therefore purified from uterine flushings and uterine fluids of
      nonpregnant pigs of mixed breed using a variety of ion-exchange chromatography
      steps. Uterine flushings and fluids contained an anionic factor(s) that at 4
      degrees C competed with 125I-labelled mouse EGF for binding to EGF receptors on
      an endometrial carcinoma cell line and stimulated DNA synthesis in Balb/c mouse
      3T3 fibroblasts. As analysed by gel filtration, uterine fluids contained a 3-6
      kDa factor that stimulated 3T3 cell DNA synthesis and was a competitor of
      cellular 125I-labelled EGF binding. Gel filtration further revealed that uterine
      flushings and fluids contained, respectively, 45 kDa and 40-70 kDa moieties that
      were mitogenic and that bound to the EGF receptor. SDS-PAGE and western blotting
      using an antiserum specific for pig EGF revealed immunoreactive forms of EGF of
      approximately 25 kDa in partially purified uterine flushings. It is concluded
      that uterine secretory EGF occurs, at least in part, as high molecular mass
      proteins. The ability of these high molecular mass EGFs to bind to and activate
      the EGF receptor suggests that they may be authentic ligands for the EGF receptor
      in utero.

PMID- 9038792
TI  - Factors controlling prostaglandin production by guinea-pig endometrial cells.
AB  - The main cell type in the guinea-pig endometrium responsible for prostaglandin
      (PG) F2 alpha production and some of the intracellular mechanisms responsible for
      PGF 2 alpha synthesis in this cell type have been investigated. The glandular
      epithelial cells and not the stromal cells were found to be the main
      prostaglandin forming cells in the endometrium. A23187 (a calcium ionophore),
      phospholipase A2 and melittin (an activator of endogenous phospholipase A2)
      increased PGF 2 alpha output from the glandular epithelial cells, although only
      the action of melittin was specific to this cell type. Phospholipase A2 also
      increased the intracellular free calcium concentration in both cell types by an
      action largely dependent upon the presence of extracellular calcium. Protein
      synthesis inhibitors (actinomycin D, cycloheximide and puromycin), oestradiol,
      progesterone and aristolochic acid (an inhibitor of phospholipase A2) reduced PGF
      2 alpha output from the glandular epithelial cells, although only the inhibitory
      action of aristolochic acid was specific. Protein synthesis inhibitors also
      reduced PGF 2 alpha output from stromal cells, and the outputs of PGE2 and 6 keto
      PGF 1 alpha from both cell types. The steroid hormones also reduced PGE2 output
      from stromal cells. The findings indicate that PGF 2 alpha production by the
      glandular epithelial cells is dependent upon fresh protein synthesis and the
      activity of endogenous phospholipase A (which is a calcium-requiring enzyme).

PMID- 9038793
TI  - Current approaches to neurobehavioural testing in occupational health.
AB  - In recent years neurobehavioural tests have been used increasingly in
      occupational settings to identify changes in cognitive function associated with
      exposure to neurotoxicants. Potential applications of these methods in
      occupational health include research, diagnosis, and screening. Applications in
      cross sectional research studies, involving the comparison of the performance of
      exposed and control groups, are well established. However, the use of such
      methods requires attention to factors other than exposure which may influence
      test performance. The validity of adapting existing test batteries for diagnosis
      or screening is questionable. Well developed techniques exist for diagnosis but
      this requires lengthy and skilled test administration and interpretation and
      cannot be accomplished with research batteries. The application of
      neurobehavioural methods for screening currently presents several difficulties.
      Current problems and future directions in this field are discussed.

PMID- 9038794
TI  - Symptoms and cholinesterase activity among rural residents living near cotton
      fields in Nicaragua.
AB  - OBJECTIVES: To explore whether symptoms resulted from pesticide spray drift on
      residentially exposed populations in rural Nicaragua. METHODS: 100 residents,
      each 10 years of age or older, were randomly selected from a Nicaraguan community
      surrounded by actively sprayed cotton fields (the exposed community) and from a
      socioeconomically similar community far from agricultural spraying (the control
      community). Subjects working with pesticides were excluded, and the study was
      conducted at the end of the 1990 cotton spraying season (August-December).
      Demographic information, exposure questions, and prevalence of 11 acute symptoms
      and 17 chronic symptoms were gathered from a structured interview. Finger stick
      erythrocyte cholinesterase (AChE) was measured with a portable colorimeter. Acute
      symptoms were grouped according to their previously known associations with
      cholinesterase (ChE) inhibitors into four ordinal categories (asymptomatic, non
      specific, possible, probable). RESULTS: Residents from the exposed community were
      significantly more likely to report recently sighting a spray plane near their
      community, exposure to pesticide from drift, crossing recently sprayed fields,
      eating home grown food, and feeling ill after drift exposure. The mean AChE value
      was significantly lower for residents of the exposed community (4.9 v 5.3 IU/dl).
      The proportion of subjects complaining of one or more chronic or acute symptoms
      was significantly higher for the exposed community (87%) than for the controls
      (53%). Odds ratios for residents in the exposed community, by symptom categories,
      were non-specific 1.6 (95% confidence interval (95% CI) 0-8 to 3.2), possible 4.1
      (95% CI 1.7 to 10.2), and probable 9.93 (95% CI 2-9 to 34.4). CONCLUSION: These
      findings indicate a strong association between exposure to aerial pesticides and
      symptoms. This study should be replicated with more quantitative exposure
      measures, for if confirmed, the results have relevance for millions in rural
      communities worldwide.

PMID- 9038795
TI  - Mortality of farmers and farmers' wives in England and Wales 1979-80, 1982-90.
AB  - OBJECTIVES: To examine the mortality patterns of male and female farmers and
      farmers' wives in England and Wales. METHODS: Information on all deaths in
      England and Wales at ages 20-74 during the periods 1979-80 and 1982-90 was
      obtained from the Office of Population Censuses and Surveys. Proportional
      mortality ratios (PMRs) and proportional cancer mortality ratios (PCMRs) were
      used to compare the mortality of farmers with that of the general working
      population, and of farmers' wives with wives of all working men. RESULTS: Farmers
      and farmers' wives had high mortality from accidents and suicide and from certain
      respiratory diseases. Mortality from hernia was also raised. Deaths from cancer
      were generally below expectations, but the PMR for prostatic cancer was 112
      (95%CI 106-118). The PMRs and PCMRs for oesophageal cancer were significantly
      increased in male farmers from two counties where cider is produced. CONCLUSIONS:
      The occupational hazards of farming continue to be associated with excess
      mortality, and most of the risks extend also to farmers' wives. Action is needed
      to reduce deaths, particularly from accidents and suicide.

PMID- 9038796
TI  - Measurement by ICP-MS of lead in plasma and whole blood of lead workers and
      controls.
AB  - OBJECTIVES: To test a simple procedure for preparing samples for measurement of
      lead in blood plasma (P-Pb) and whole blood (B-Pb) by inductively coupled plasma
      mass spectrometry (ICP-MS), to measure P-Pb and B-Pb in lead workers and
      controls, and to evaluate any differences in the relation between B-Pb and P-Pb
      between people. METHODS: P-Pb and B-Pb were measured by ICP-MS in 43 male lead
      smelter workers and seven controls without occupational exposure to lead. For
      analysis, plasma and whole blood were diluted 1 in 4 and 1 in 9, respectively,
      with a diluted ammonia solution containing Triton-X 100 and EDTA. The samples
      were handled under routine laboratory conditions, without clean room facilities.
      RESULTS: P-Pb was measured with good precision (CV = 5%) even at concentrations
      present in the controls. Freeze storage of the samples had no effect on the
      results. The detection limit was 0.015 microgram/l. The P-Pb was 0.15 (range 0.1
      0.3) microgram/l in controls and 1.2 (0.3-3.6) micrograms/l in lead workers,
      although the corresponding B-Pbs were 40 (24-59) micrograms/l and 281 (60-530)
      micrograms/l (1 microgram Pb/I = 4.8 nmol/l). B-Pb was closely associated with P
      Pb (r = 0.90). The association was evidently non-linear; the ratio B-Pb/P-Pb
      decreased with increasing P-Pb. CONCLUSIONS: By means of ICP-MS and a simple
      dilution procedure, P-Pb may be measured accurately and with good precision down
      to concentrations present in controls. Contamination of blood at sampling and
      analysis is no major problem. With increasing P-Pb, the percentage of lead in
      plasma increases. In studies of lead toxicity, P-Pb should be considered as a
      complement to current indicators of lead exposure and risk.

PMID- 9038797
TI  - Respiratory health of workers exposed to low levels of chromium in stainless
      steel production.
AB  - OBJECTIVES: To determine whether occupational exposure to chromite, trivalent
      chromium, or hexavalent chromium causes respiratory diseases, an excess of
      respiratory symptoms, a decrease in pulmonary function, or signs of
      pneumoconiosis among workers in an integrated chain of stainless steel
      production. METHODS: This cross sectional study was carried out in 1993 and the
      inclusion criterion was a minimum of eight years of employment in the same
      production department. A self administered questionnaire was collected, and
      spirometry, measurement of diffusing capacity, chest radiography, and laboratory
      tests were carried out by a mobile research unit. RESULTS: There were 221 workers
      in the exposure groups and 95 in the control group. The average duration of
      employment was 18 years. No significant differences in the odds ratios (ORs) of
      the symptoms were found between the exposure and the control groups. In a
      logistic regression analysis age and smoking significantly explained the
      occurrence of most of the respiratory symptoms. The smokers in the chromite group
      had significantly lower forced vital capacity (FVC), forced expiratory volume in
      one second (FEV1), and diffusing capacity than the corresponding values of the
      control group. The analysis of variance between study groups, smoking, and
      exposure time, without modelling for interactions, showed that the chromite group
      had lower values for FVC, FEV1, and diffusing capacity than the other groups. The
      occurrence of small opacities was more frequent on the chest radiographs of the
      workers in the chromite group. CONCLUSIONS: An average exposure time of 18 years
      in ferrochromium and stainless steel production and exposure to dusts containing
      low concentrations of hexavalent or trivalent chromium do not lead to any
      respiratory changes detectable by lung function tests or radiography nor to any
      increase in symptoms of respiratory diseases. The lung function values were lower
      and the occurrence of radiological findings was more frequent among the workers
      from the chromite mine than among the controls. The difference was partly caused
      by differences in age and smoking habits, but evidently also partly by higher
      exposures more than two decades ago or by the fibrous components of the dust.

PMID- 9038798
TI  - Airway responsiveness, respiratory symptoms, and exposures to soluble oil mist in
      mechanical workers.
AB  - OBJECTIVES: To assess the relation between measured levels of exposure to soluble
      oil mists in a plant manufacturing ball bearings, and both respiratory symptoms
      and airway responsiveness in the workforce. METHODS: 114 male workers exposed to
      oil mist and 55 unexposed male controls from nearby factories were studied.
      Soluble oil mist concentrations were measured with area samplers. Respiratory
      symptoms were assessed by questionnaire and measurement of airway responsiveness
      to methacholine with an abbreviated method. Subjects were labelled positive to
      methacholine airway challenge (MAC+) if forced expiratory volume in one second
      (FEV1) fell by > or = 20%. The linear dose-response slope was calculated as the
      percentage fall in FEV1 at the last dose divided by the total dose given.
      RESULTS: Geometric mean concentrations of oil mists ranged from 0.65 mg/m3 (GSD
      1.29) to 2.20 mg/m3 (GSD 1.55) based on 92 measurements obtained from 1979-93.
      The prevalence of chronic cough or phlegm, bouts of bronchitis, and dyspnoea was
      greater among exposed workers than among controls (odds ratio (OR) 4.64, P =
      0.002 for chronic cough and phlegm). After adjustment for smoking and age,
      dyspnoea was significantly related to an index of cumulative exposure to oil mist
      (OR 1.44, P = 0.006/10 y.mg/m3). The proportion of MAC+ subjects was similar in
      the two groups. However, after adjustment for baseline FEV1 and age, the dose
      response slope was significantly steeper among exposed workers than among
      controls (P = 0.01), a finding indicating airway hyperresponsiveness in the
      exposed workers. Furthermore, the dose-response slope was significantly related
      to baseline FEV1, age, and, after adjustment for FEV1, the index of cumulative
      exposure to oil (P = 0.004). CONCLUSION: Subjects with exposure to soluble oil
      mist in the metal industry are at risk of developing both respiratory symptoms
      and airway hyperresponsiveness.

PMID- 9038799
TI  - Longitudinal decline in lung function in patients with occupational asthma due to
      western red cedar.
AB  - BACKGROUND: There are few reports about longitudinal changes in lung function in
      asthmatic patients. Patients with asthma had a greater loss of lung function than
      normal healthy adults. To date, there have been no studies about the longitudinal
      changes in lung function in patients with occupational asthma. METHODS: 280 male
      patients with red cedar asthma (RCA) who were followed up for at least one year
      were the study group. The exposed controls consisted of 399 male sawmill workers.
      Forced expiratory volume in one second (FEV1) was measured with a Collins water
      spirometer. Changes in FEV1 over time (FEV1 slope) were calculated by a two point
      method for each subject. Atopy was considered to be present if the subjects
      showed at least one positive response to three allergens by skin prick test.
      RESULTS: Multiple regression analysis was carried out to examine factors that
      might affect longitudinal decline in FEV1. Patients with RCA who were still
      exposed had a greater decline in FEV1 slope (-26 ml/y) than sawmill workers.
      Smokers also showed a greater rate of decline in FEV1 (-43 ml/y) than non
      smokers. CONCLUSIONS: Patients with RCA who continued to be exposed had a greater
      rate of decline in FEV1 than sawmill workers. Early diagnosis of occupational
      asthma and removal of these patients from a specific sensitiser is important in
      the prevention of further deterioration of lung function and respiratory
      symptoms.

PMID- 9038800
TI  - Self reported rate of occupational asthma in Sweden 1990-2.
AB  - OBJECTIVES: To estimate the annual rates of self reported occupational asthma in
      different occupational groups in Sweden. METHODS: All claims of occupational
      asthma 1990-2 in the Swedish register of reported occupational diseases were
      classified according to occupation. The number of people employed in each
      occupational group in the general population was obtained from the 1990 national
      census. Reporting rates (cases/million/ year) were calculated for each occupation
      with more than five reported cases, according to sex and age (20 to 64 years, and
      20 to 44 years). RESULTS: 1010 cases were reported giving an annual crude
      reporting rate of 80/million (95% confidence interval (95% CI) 70 to 90). For
      men, the crude reporting rate was 91/million (95% CI 84 to 98), and for women
      70/million (95% CI 80 to 106). The highest reporting rates were among male bakers
      (775/million), furnacemen (702/million), male welders (647/million), female
      chemical and plastic production workers (629/million), and female poultry and
      dairy farm workers (602/million). CONCLUSIONS: A surveillance system based on
      self reporting is influenced by considerable bias, especially reporting bias.
      However, results for the specific occupations with high rates were similar to
      those found with other surveillance systems. This indicates that our system is a
      useful one.

PMID- 9038801
TI  - Non-fibrous inorganic particles in bronchoalveolar lavage fluid of pottery
      workers.
AB  - AIM: To study the actual exposure of pottery workers to silica particles, as
      their risk of silicosis is potentially high because of the presence of inhalable
      crystalline silica particles in the workplace. METHODS: Nine pottery workers
      underwent bronchoalveolar lavage. The recovered fluid was analysed for
      cytological and mineralogical content by analytical transmission electron
      microscopy. The data were compared with those obtained from a control group
      composed of seven patients with sarcoidosis and six patients with haemoptysis.
      RESULTS: Cytological results showed a similar profile in exposed workers and
      controls, whereas in patients with sarcoidosis a lymphocytic alveolitis was
      found. Microanalysis of the particulate identified the presence of silicates,
      CRSs, and metals. Pottery workers had higher numbers of total particles and CRSs,
      and had a higher silicate/metal ratio. In five workers, the presence of zirconium
      silicate was also detected. Patients with sarcoidosis had the lowest number of
      particles, and an inverted silicate/metal ratio. CONCLUSION: Microanalysis by
      transmission electron microscope can provide useful information to assess
      occupational exposure to dusts.

PMID- 9038802
TI  - Comparison of eight and 12 hour shifts: impacts on health, wellbeing, and
      alertness during the shift.
AB  - OBJECTIVES: The generally agreed view is that there is no ideal shift system, and
      that most systems will have both advantages and disadvantages. As such, attention
      has been placed on trying to identify good and bad features of shift systems,
      with a view to minimising the possible ill health as a consequence of shiftwork.
      The present study focuses on the duration of the shift and looks at the
      implications for individual health, wellbeing, and alertness during the shift of
      extending the shift from the traditional eight hours to 12. METHODS: Two groups
      of chemical workers, one working 12 hour shifts and the other working eight hour
      shifts, took part. All completed a modified version of the standard shiftwork
      index (SSI), a set of self reported questionnaires related to health and
      wellbeing. RESULTS: The two groups did not differ on most outcome measures,
      although the differences that did exist suggested advantages for the 12 hour
      shift workers over the eight hour shift workers; with the notable exception of
      rated alertness at certain times of day. CONCLUSIONS: The results are explained
      in terms of the design of the 12 hour shift system and the specific sequencing of
      shifts that seem to minimise the potential for the build up of fatigue. Although
      the current data moderately favour 12 hour shifts, a cautionary note is sounded
      with regard to the implications of the alertness ratings for performance and
      safety.

PMID- 9038803
TI  - Lymphohaematopoietic malignancies and quantitative estimates of exposure to
      benzene in Canadian petroleum distribution workers.
AB  - OBJECTIVE: To evaluate the relation between mortality from lymphohaematopoietic
      cancer and long term, low level exposures to benzene among male petroleum
      distribution workers. METHODS: This nested case control study identified all
      fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of
      the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkin's
      lymphoma. A four to one matching ratio was used to select a stratified sample of
      controls from the same cohort, controlling for year of birth and time at risk.
      Industrial hygienists estimated workplace exposures for benzene and total
      hydrocarbons, without knowledge of case or control status, for combinations of
      job, location, and era represented in all work histories. Average daily benzene
      concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs.
      Company medical records were used to abstract information on other potential
      confounders such as cigarette smoking, although the data were incomplete. Odds
      ratios (ORs) were calculated with conditional logistic regression techniques for
      several exposure variables. RESULTS: Risks of leukaemia, non-Hodgkin's lymphoma,
      and multiple myeloma were not associated with increasing cumulative exposure to
      benzene or total hydrocarbons. For leukaemia, the logistic regression model
      predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene.
      Duration of exposure to benzene was more closely associated with risk of
      leukaemia than other exposure variables. It was not possible to completely
      control for other risk factors, although there was suggestive evidence that
      smoking and a family history of cancer may have played a part in the risk of
      leukaemia. CONCLUSION: This study did not show a relation between
      lymphohaematopoietic cancer and long term, low level exposures to benzene. The
      power of the study to detect low-such as twofold-risks was limited. Thus, further
      study on exposures to benzene in this concentration range are warranted.

PMID- 9038804
TI  - Investigation of a cluster of pituitary adenomas in workers in the aluminum
      industry.
AB  - OBJECTIVE: Four cases of pituitary adenoma among employees at a primary aluminum
      production factory were identified over a five year period by a community
      physician. The objective of this investigation was to determine whether there has
      been a comparable high incidence in other aluminum factories, and if particular
      jobs, departments, or activities in the industry are associated with higher rates
      of the disease. METHOD: Pituitary adenoma in employees at all United States
      factories of the company for the years 1989-94 was assessed by a search of a
      health data information bank and an insurance data base covering present and past
      employees of the corporation. The incidence in the aluminum workers was estimated
      and compared with the workers in the index plant. A nested case control study was
      conducted to compare employment histories of identified cases with those of age
      and sex matched controls selected from the health information data base. RESULTS:
      25 cases, including the index cases, were identified which had been diagnosed
      during the period 1989-94. The resulting rate of 10.4/100,000 person-years was
      much lower than that at the index plant. Case-control analysis showed no coherent
      pattern of location, department, or job significantly associated with risk. In
      particular, jobs and departments associated with exposures common to aluminum
      smelting-such as coal tar pitch volatiles and fluorides-were shown to be uncommon
      among cases compared with age and sex matched controls. CONCLUSION: Overall,
      despite the unprecedented cluster at a single plant, no strong evidence was found
      that the rate of pituitary adenoma is increased in aluminum workers generally. We
      found no association with any work activity or location in the industry to
      suggest a work related or exposure related cause for the disease.

PMID- 9038805
TI  - Cancer mortality among local authority pest control officers in England and
      Wales.
AB  - OBJECTIVE: To examine cancer mortality by tumour site among local authority pest
      control officers. METHODS: Prospective mortality study, and follow up to the end
      of 1994, of 1485 male pest control officers aged between 17 and 69 and employed
      in 296 local authorities in England and Wales for at least six months between
      January 1980 and April 1984. Observed numbers of deaths were compared with those
      expected on the basis of the rates for relevant calendar year, cause, sex, and
      age specific groups for England and Wales. RESULTS: 200 deaths occurred during
      the follow up period of which 65 were certified as due to malignant neoplasms. No
      tumour type showed significantly more deaths than expected. Total all cause, lung
      cancer, and respiratory disease mortality were significantly lower than expected.
      CONCLUSIONS: 15 year follow up of a group of men handling a wide range of
      pesticides did not show any significant risk of cancer. This may be partially
      explained by the healthy worker effect and also the limited power of the study to
      detect significant increases in the less common tumours. Further long term follow
      up of this cohort will continue. Chemical control of pests that can cause human
      disease and can contaminate food and water has been, and will continue to be, a
      major public health measure. It is important to ensure that the health of those
      applying pesticides is not at excess risk. Negative results are important.

PMID- 9038806
TI  - New perspectives in a gustatory physiology: transduction, development, and
      plasticity.
AB  - Major advances in the understanding of mammalian gustatory transduction
      mechanisms have occurred in the past decade. Recent research has revealed that a
      remarkable diversity of cellular mechanisms are involved in taste stimulus
      reception. These mechanisms range from G protein-and second messenger-linked
      receptor systems to stimulus-gated and stimulus-admitting ion channels. Contrary
      to widely held ideas, new data show that some taste stimuli interact with
      receptive sites that are localized on both the apical and basolateral membranes
      of taste cells. Studies of taste system development in several species indicate
      that the transduction pathways for some stimuli are modulated significantly
      during the early postnatal period. In addition, recent investigations of adult
      peripheral gustatory system plasticity strongly suggest that the function of the
      Na+ sensing system can be modulated by circulating hormones, growth factors, or
      cytokines.

PMID- 9038807
TI  - Properties of single Drosophila Trpl channels expressed in Sf9 insect cells.
AB  - The transient receptor potential (trp)-like (trpl) gene is thought to encode an
      ion channel important for signal transduction in Drosophila photoreceptor cells.
      Consistent with this hypothesis, heterologous expression of the trpl-encoded
      protein (Trpl) is associated with the appearance of an outwardly rectifying,
      nonselective cation current. In the present study, single channels were recorded
      in cell-attached, inside-out, and outside-out membrane patches from Sf9 insect
      cells infected with recombinant baculovirus-containing trpl cDNA under control of
      the polyhedrin promoter. The single-channel current-voltage relationship was
      linear from -100 to +80 mV with a slope conductance of 89-110 pS. The probability
      of opening was voltage sensitive, increasing at positive potentials contributing
      to the outwardly rectifying properties of the whole cell currents. The single
      channels 1) were never observed in Sf9 cells infected with recombinant
      baculovirus containing the B2 bradykinin receptor cDNA or in noninfected Sf9
      cells; 2) appear at the same time postinfection as the Trpl whole cell current;
      3) were nonselective with respect to Na+, Ca2+, and Ba2+; 4) were blocked by 1-2
      mM La3+ and Gd3+ (but not 10 microM); and 5) were blocked by 4-8 mM Mg2+. The
      single Trpl channel activity increased spontaneously with time after patch
      formation, and the activity was further increased by application of bradykinin to
      cells expressing both the B2 bradykinin receptor and the Trpl protein. These
      results suggest that this single-channel activity reflects expression of the Trpl
      protein and provides conclusive evidence that trpl encodes a nonselective cation
      channel consistent with its proposed role in Drosophila phototransduction.

PMID- 9038808
TI  - Regulation of inducible nitric oxide synthase expression in L6 rat skeletal
      muscle cells.
AB  - Cytokine-stimulated expression of inducible type of nitric oxide synthase (iNOS)
      seems to be regulated by various signal pathways in a cell-specific manner. In
      this study, we examined how it was regulated in L6 rat skeletal muscle cells. In
      L6 cells, the combination of interleukin-1 beta and interferon-gamma induced a
      marked accumulation of nitrite, a stable metabolite of nitric oxide. In parallel
      with this reaction, iNOS mRNA expression was achieved at a maximum between 3 and
      6 h, and iNOS protein was detectable at 6 h and peaked at 24 h after stimulation.
      Tyrosine kinase inhibitors, herbimycin A, and genistein suppressed cytokine
      induced iNOS expression and nitrite production. Forskolin, an adenosine 3',5'
      cyclic monophosphate-dependent protein kinase (PKA) activator, and phorbol 12
      myristate 13-acetate, a protein kinase C (PKC)-activating phorbol ester, enhanced
      these cytokine-induced reactions. These results indicate that iNOS expression by
      cytokines is mediated via a protein tyrosine kinase-dependent pathway and is
      positively modulated by both PKA- and PKC-dependent pathways in this cell type.

PMID- 9038809
TI  - BAY K 8644 and ClO4- potentiate caffeine contracture without Ca2+ release channel
      activation.
AB  - Effects of perchlorate (ClO4-) and BAY K 8644 on caffeine contracture and Ca2+
      release channel current were studied in frog skeletal muscle. Single fibers
      produced a small transient contracture on addition of 2.2 mM caffeine. ClO4 at 10
      mM enhanced caffeine contracture 3.7-fold. This effect was inhibited by 10 microM
      nifedipine pretreatment. An increase in caffeine contracture was also obtained
      after exposure to 0.1 microM BAY K 8644 for 1 h. At 20 mM, external K+
      potentiated caffeine contracture 2.2-fold. ClO4- (< 10 mM) and BAY K 8644 (0.1-1
      microM) did not affect open probability (Po), unitary conductance, and open and
      closed time constants of the Ca2+ release channel current. BAY K 8644 at 0.1
      microM did not further enhance the channel that had been activated by 2 mM
      caffeine. However, 20-30 mM ClO4 increased Po significantly and led the channel
      to a long open state by increasing the slow open time constant and decreasing the
      fast closed time constant. These results suggest that binding of ClO4 and BAY K
      8644 to dihydropyridine receptors elicits a further increase in Ca2+ release from
      the sarcoplasmic reticulum.

PMID- 9038810
TI  - Role of vacuolation in the death of gastric epithelial cells.
AB  - The effect of vacuolation on survival of gastric epithelial cells was studied in
      rabbit gastric glands (RGG) incubated with ammonia and bafilomycin A1, a potent
      inhibitor of vacuolar ATPase activity. In ammonia, large vacuoles formed and cell
      survival was reduced to 47.2 +/- 3.4% at 6 h (59.5 +/- 3.8%, buffer). Bafilomycin
      A1 added at the start to RGG incubated with ammonia inhibited vacuole formation
      but did not improve cell survival (48.7 +/- 2.8% at 6 h). Bafilomycin A1 added 1
      2 h after addition of ammonia reduced the size of vacuoles but did not alter cell
      survival. Cell survival was not affected by inhibiting protein synthesis. When
      incubated with ammonia, parietal cells dissociated from the gland and ruptured.
      After this, chief cells condensed and formed expensive blebs that contained
      fragmented nuclei. We conclude that 1)ammonia-induced vacuolation of gastric
      epithelial cells does not influence cell survival, 2) ammonia facilitates
      necrosis in parietal cells and apoptosis in chief cells, and 3) chief cell
      survival, in some manner, may be dependent on parietal cells.

PMID- 9038811
TI  - Induction of heme oxygenase-1 (HSP32) mRNA in skeletal muscle following
      contractions.
AB  - The capacity of preexisting antioxidant pathways to handle oxidative stress
      during exercise may be complemented by the synthesis of inducible heat stress
      proteins (HSP). Our purpose was to determine if the amount of mRNA for HSP32, a
      major oxidative stress protein, was increased in muscle after repetitive
      contractions. Reverse transcriptase-polymerase chain reaction analysis showed
      that HSP32 mRNA (normalized to alpha-actin mRNA) was increased about seven- and
      about fourfold (P < 0.35) immediately after 1 h of exhaustive running and after 3
      h of muscle contractions (10 Hz nerve stimulation), respectively. Northern blot
      analysis revealed that HSP70 mRNAs were 3.5- to 15.5-fold above control value (P
      < 0.05), whereas the content of another oxidative stress protein mRNA (macrophage
      stress protein 23) was unchanged 0 h after contractions. The relative increase in
      HSP32 mRNA was found to be dependent on active tension generation; passive
      tension did not increase the HSP32-to-actin mRNA ratio. Increases in HSP32 mRNA
      may underlie an inducible antioxidant pathway in muscle responsive to metabolic
      stresses associated with repeated muscle contractions.

PMID- 9038812
TI  - Fast and slow skeletal muscles express a common basic profile of
      acetylcholinesterase molecular forms.
AB  - Recent evidence suggests that the high content of acetylcholinesterase (AChE)
      globular form G4, characteristic of fast muscles, is controlled by phasic high
      frequency activity performed by these muscles. This indicates that inactive,
      though still innervated, fast muscles should be devoid of their characteristic G4
      pool. Accordingly, in the absence of phasic activity, both fast and slow muscles
      should exhibit a common basic profile of AChE molecular forms of the slow type.
      We first tested this hypothesis by examining the AChE content in cultures of
      myotubes obtained from the fusion of satellite cells originating from fast and
      slow muscles. These two cell populations produced AChE molecular-form profiles of
      the slow type characterized by modest levels of G4 together with an increased
      proportion of the asymmetric forms A8 relative to A12. Second, we determined the
      impact of muscle paralysis on the specific content of AChE molecular forms of
      adult rat fast and slow muscles. Complete paralysis of hindlimb muscles was
      achieved by chronic superfusion of tetrodotoxin (TTX) onto the sciatic nerve. Ten
      days after TTX inactivation, the distributions of AChE molecular forms of both
      fast extensor digitorum longus (EDL) and plantaris muscles were transformed into
      ones resembling the slow soleus, the latter showing no significant modifications
      in its AChE profile. Finally, we investigated the impact of nerve-mediated phasic
      high-frequency stimulation of TTX-inactivated fast and slow muscles on the
      content of AChE molecular forms. This stimulation produced a profile of AChE
      molecular forms similar to that observed in control EDL muscles, indicating that
      phasic activation counteracted the TTX-induced transformation in the distribution
      of AChE molecular forms in fast EDL muscles. Together, these results are
      consistent with the proposal that adult fast muscles constitutively express a
      basic profile of AChE molecular forms of the type displayed by slow muscles, onto
      which varying levels of G4 are added according to the amount of phasic activity
      performed by the muscles.

PMID- 9038813
TI  - beta-Adrenergic modulation of Ba2+ currents and K+ contractures in frog slow
      skeletal muscle fibers.
AB  - beta-Adrenergic modulation of the Ba2+ current (IBa) and K+ contracture in slow
      skeletal muscle fibers of the frog (Rana pipiens) were investigated in intact
      fibers with the three-microelectrode voltage-clamp technique and isometric
      tension measurements. Application of epinephrine (10(-6) to 10(-5) M) to the bath
      increased the amplitude of IBa. This increase was blocked by the beta-antagonist
      propranolol (3 microM), and a similar increase was observed with the beta
      specific agonist isoproterenol (1 microM). Thus the epinephrine effect was
      mediated mainly by beta-adrenergic receptors. External application of permeable 8
      bromoadenosine 3',5'-cyclic monophosphate (0.5 mM) increased the amplitude of
      both IBa and K+ contractures. The present results suggest that beta-adrenergic
      modulation of IBa in slow skeletal muscle fibers could reflect a modulation of
      Ca2+ channels via adenosine 3',5'-cyclic monophosphate (cAMP). cAMP (0.5 mM) also
      potentiated the K(+)-evoked tension in these slow fibers. The physiological
      contribution made by the modulation of slow skeletal muscle Ca2+ channels to the
      increase in tension is still not completely understood.

PMID- 9038814
TI  - Protein kinase A activity modulates natriuretic peptide-dependent cGMP
      accumulation in renal cells.
AB  - The purpose of this work was to examine whether the level of cAMP accumulation
      and protein kinase A (PKA) activity influence atrial natriuretic factor (ANF)
      dependent guanosine 3',5'-cyclic monophosphate (cGMP) production in two renal
      cell types: rabbit cortical vascular smooth muscle cells (RCSMC) and SV-40
      transformed human glomerular visceral epithelial cells (HGVEC-SV1). N-[2-(p
      bromocinnamylamino)ethyl]- 5-isoquinolinesulfonamide (H-89), a PKA inhibitor,
      decreased ANF-stimulated cGMP production in RCSMC in a time- and concentration
      dependent manner. ANF-stimulated cGMP production was markedly inhibited after
      prolonged 9- and 18-h incubations with 25 microM H-89 (52 and 65%, respectively)
      but was not altered after exposure of cells to this agent for 1 h. 1-(5
      Isoquinolinylsulfonyl)-2-methylpiperazine and N-(2-[methylamino]ethyl)-5
      isoquinolinesulfonamide, protein kinase inhibitors not selective for PKA, did not
      reproduce the effect of H-89, even at higher concentrations (50 and 100 microM).
      Cycloheximide (10 microM), a protein synthesis inhibitor, limited the inhibitory
      effect of H-89, although alone it did not modify the ANF-stimulated cGMP
      production. H-89 did not affect cGMP production when it was stimulated by SIN-1,
      a nitric oxide donor. Prolonged incubation (18 h) with 8-bromo cAMP or cholera
      toxin, an activator of Gs protein resulting in adenylate cyclase stimulation,
      enhanced ANF-dependent cGMP production by 225 and 176%, respectively. This
      stimulatory effect was blocked by 25 microM H-89. 125I-ANF binding to RCSMC at 4
      degrees C was not affected by preincubation of the cells with H-89. There was a
      44% decrease in the expression of ANF C receptors measured as the ANF-(4-23)
      displaceable 125I-ANF binding at 37 degrees C, which could not, however, explain
      the inhibitory effect of H-89 on cGMP production. Modulation of ANF- and C-type
      natriuretic peptide-dependent cGMP production by H-89 and cholera toxin was also
      found in HGVEC-SV1 with the same characteristics as in RCSMC. Taken together,
      these results suggest that PKA activity controls the function of natriuretic
      peptide guanylate cyclase-coupled receptors in the two cell types studied. PKA
      dependent inhibition of a negatively regulatory protein distinct from the
      receptor itself seems necessary for a full cGMP response.

PMID- 9038815
TI  - Heterologous expression of rat NHE4: a highly amiloride-resistant Na+/H+
      exchanger isoform.
AB  - Molecular cloning and expression have previously defined three members of the
      Na+/H+ exchanger (NHE) gene family NHE1 and NHE2 are sensitive to inhibition by
      amiloride and its 5'-amino alkyl-substituted analogues, whereas NHE3 is quite
      resistant to amiloride inhibition. Each of these exchangers has narrowly defined
      cation specificities for Na+ and Li+. Expression studies with NHE4 have not been
      as successful, with only a description of modest expression of activity (C.
      Bookstein, M. W. Musch, A. DePaoli, Y. Xie, M. Villereal, M. C. Rao, and E. B.
      Chang. J. Biol. Chem. 269: 29704-29709, 1994). We now report that NHE4 activity
      in stably transfected fibroblasts is activated by 4,4'-diisothiocyanostilbene
      2,2'-disulfonic acid (DIDS), permitting functional characterization of this NHE
      isoform. The activating effect of DIDS was unique among the disulfonic stilbenes,
      and competition studies suggested a cross-linking mechanism. NHE4 is extremely
      resistant to amiloride and ethylisopropylamiloride inhibition and, unlike other
      NHE isoforms, affects K+/H+ exchange as well as Na+/H+ and Li+/H+ exchange. These
      findings demonstrate that NHE4 is a functionally distinct member of the NHE gene
      family and suggest a unique physiological role for this cation/H+ exchanger.

PMID- 9038816
TI  - Glutathione redox cycle regulates nitric oxide-mediated glyceraldehyde-3
      phosphate dehydrogenase inhibition.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as a
      potential target for nitric oxide (NO)-mediated cellular toxicity. We have
      previously shown that NO inhibits GAPDH by S-nitrosylation of the active site
      cysteine residue, which is reversed by low-molecular-weight thiols. Because
      endothelial cells contain high concentrations of low-molecular-weight thiols,
      principally glutathione, we investigated the effect of NO on GAPDH activity in
      intact endothelial cells and the influence that cellular glutathione has on GAPDH
      inhibition. Our results show that incubation of cells with an exogenous NO
      generating system resulted in inhibition of GAPDH activity. The mechanism for
      inhibition appears to involve reversible modification of GAPDH because addition
      of thiols to cell extracts restored activity. Furthermore, cells were able to
      completely recover GAPDH activity after removal of the NO-generating system.
      Recovery did not require de novo protein synthesis. Depletion of cellular
      glutathione levels by treatment of cells with buthionine sulfoximine resulted in
      greater NO-mediated GAPDH inhibition as well as a lesser ability to recover
      activity. Finally, disruption of the glutathione redox cycle with the glutathione
      reductase inhibitor, 1,3-bis(2-chloroethyl)-1-nitrosourea, increased the extent
      of NO-mediated GAPDH inhibition and decreased both the rate and degree of
      recovery of GAPDH-activity. These results suggest that the glutathione redox
      cycle plays an important role not only in regulating the extent of NO-mediated
      GAPDH inhibition but also in the ability of endothelial cells to recover from NO
      mediated GAPDH inhibition.

PMID- 9038817
TI  - Expression of the sodium-chloride cotransporter in osteoblast-like cells: effect
      of thiazide diuretics.
AB  - The use of thiazide diuretics is associated with increased bone mineral density
      and, in some studies with reduced incidence of fractures, suggesting a potential
      role for these drugs in the treatment of osteoporosis. Our objective was to
      examine the effects of thiazides on osteoblast-like cells using the rat UMR-106
      osteosarcoma cell line. Treatment of UMR-106 cells with chlorothiazide caused
      membrane depolarization and a rise of intracellular calcium but had no effect on
      adenosine 3,5'-cyclic monophosphate accumulation. The rise of intracellular
      calcium was partially inhibited by nifedipine and removal of extracellular
      calcium, indicating calcium uptake from the extracellular media, as well as by
      thapsigargin or dantrolene, indicating contributions from calcium release from
      intracellular stores. Reverse transcriptase-polymerase chain reaction was used to
      isolate a partial cDNA clone for the thiazide-sensitive sodium-chloride
      cotransporter from UMR-106 cells that hybridized to 5.0- and 11.0-kilobase mRNAs
      when Northern blot analysis was conducted. Antisense oligonucleotides to the
      sodium-chloride cotransporter specifically inhibited the chlorothiazide-induced
      depolarization and rise of intracellular calcium and reduced immunofluorescence
      staining for the sodium-chloride cotransporter protein in UMR-106 cells. We
      conclude that thiazide diuretics inhibit sodium-chloride cotransporter activity
      in UMR-106 cells, thereby altering intracellular calcium regulation. These
      results provide evidence for direct effects of thiazide diuretics on bone cells.

PMID- 9038818
TI  - Gap junctions in human umbilical cord endothelial cells contain multiple
      connexins.
AB  - We investigated the expression pattern of gap junctional proteins (connexins, Cx)
      in situ and in vitro and their functional characteristics in cultured human
      umbilical vein endothelial cells (HUVEC) and cultured human umbilical artery
      endothelial cells (HUAEC). In both arteries and veins, Cx37, Cx40, and Cx43 could
      be detected in situ and in vitro (passages 2-4). Distribution patterns of Cx40
      and Cx43 were homogeneous in situ but more heterogeneous in vitro. Cx37 is
      heterogeneously expressed both in situ and in vitro. Among most cells, no Cx37
      staining could be detected; when present, it was found as bright spots between
      some clusters of cells. Cx40 was more abundant in cultured arterial endothelium
      than in cultured venous endothelium. Dye-coupling experiments with Lucifer yellow
      CH revealed extensive dye spread in HUVEC (15.2 +/- 0.4, mean +/- SE, n = 110)
      but was significantly restricted in HUAEC (9.8 +/- 0.3, n = 110).
      Electrophysiological gap junctional characteristics were determined in cultured
      HUVEC and HUAEC pairs by use of the dual voltage-clamp technique. In contrast to
      the dye-coupling experiments, mean macroscopic electrical conductance was
      significantly larger for HUAEC pairs (31.4 +/- 6.0 nS, n = 12) than for HUVEC
      pairs (16.6 +/- 2.8, n = 18). In HUVEC, we measured multiple single gap
      junctional channel conductances in the range of 19-75 pS. Interestingly,
      additional conductances of 80-200 pS were measured in HUAEC, possibly partially
      reflecting activity of channels formed of Cx40, which are more abundant in the
      cultured arterial endothelial cells.

PMID- 9038819
TI  - Noncoordinated expression of alpha-, beta-, and gamma-subunit mRNAs of epithelial
      Na+ channel along rat respiratory tract.
AB  - Na+ reabsorption from the epithelial surface of the respiratory tract plays a
      fundamental role in respiratory physiology. As in the epithelia of the renal
      collecting tubule and distal colon, Na+ enters across the luminal surface of
      respiratory epithelial cells via a recently cloned amiloride-sensitive
      multisubunit (alpha, beta, gamma) epithelial Na+ channel. We have examined the
      cellular expression at the mRNA level of the alpha-, beta-, and gamma-subunits of
      rat epithelial Na+ channel (rENaC) in the rat lung and upper airway epithelial
      cells using in situ hybridization. A large prevalence of alpha- and gamma-rENaC
      subunit expression (over beta) was found in tracheal epithelium, in a
      subpopulation of alveolar cells, presumably type II pneumocytes, and in nasal and
      tracheal gland acini. In contrast, equivalent levels of expression of all three
      subunits were detected in bronchiolar epithelium and in rat nasal gland ducts.
      This diversity of expression may reflect cell-specific functions of the amiloride
      sensitive Na+ channel along the respiratory tract.

PMID- 9038820
TI  - Modulation of CFTR chloride channels by calyculin A and genistein.
AB  - Modulation of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-
      channel by calyculin A and genistein was studied in Hi-5 insect cells infected
      with baculovirus containing the wild-type CFTR cDNA. In cell-attached patches,
      CFTR channel activity was not observed until stimulated by forskolin in 90% of
      the cells, suggesting a low level of basal adenosine 3',5'-cyclic monophosphate
      activity. Calyculin A, a specific inhibitor of phosphatases 1 and 2A, increased
      forskolin-induced CFTR activity by 17.2-fold. CFTR channel currents did not
      deactivate completely after forskolin was withdrawn in the continued presence of
      calyculin A. Genistein enhanced forskolin-induced CFTR activity by 44.9-fold but
      could neither activate the CFTR by itself nor prevent complete deactivation on
      removal of forskolin. Genistein together with calyculin A could adequately
      prevent deactivation of CFTR currents. Noise analysis of the macroscopic CFTR
      currents revealed significant differences in the mean current-variance
      relationship and the corner frequency of the noise spectra between currents
      activated by forskolin plus genistein and those activated by forskolin plus
      calyculin A. Furthermore, genistein enhanced CFTR activity induced by saturating
      concentrations of forskolin and calyculin A. Our results suggest that genistein
      and calyculin A modulate the CFTR by different mechanisms and that genistein
      might inhibit calyculin A-insensitive dephosphorylation of the CFTR.

PMID- 9038821
TI  - Insulin-mimetic agents vanadate and pervanadate stimulate glucose but inhibit
      amino acid uptake.
AB  - The protein tyrosine phosphatase (PTP) inhibitors vanadate and pervanadate (pV)
      exert insulin-like biologic effects. In cultured differentiated rat L6 skeletal
      muscle cells, vanadate and pV stimulated 2-deoxy-D-[3H]glucose uptake in a dose-
      and time-dependent manner. There was no increase in maximum stimulation by
      additional insulin. In contrast, whereas insulin stimulated
      [14C]methylaminoisobutyric acid (MeAIB) uptake, basal uptake was inhibited by
      vanadate and pV. Insulin-stimulated MeAIB uptake was also inhibited in a dose
      dependent manner and completely abolished by 5 mM vanadate or 0.1 mM pV. The
      inhibitory effect on basal MeAIB uptake was associated with a decrease in
      transporter affinity and a small decrease in maximum transport capacity, whereas
      the insulin-stimulated increase in maximum transport capacity was completely
      inhibited. Inhibition of MeAIB uptake by vanadate and pV was not blocked by
      cycloheximide, and oubain did not inhibit uptake. Vanadate also inhibited amino
      acid deprivation-stimulated MeAIB uptake. Insulin-stimulated MeAIB uptake was
      also inhibited in rat hepatoma cells. Thus vanadate and pV mimic insulin to
      stimulate glucose uptake but inhibit system A amino acid uptake. The relative
      inhibitory concentrations of vanadate and pV suggest that the mechanism may
      involve PTP inhibition.

PMID- 9038822
TI  - An electrophysiological study of neurons in the horizontal limb of the diagonal
      band of Broca.
AB  - We examined the morphological and electrophysiological properties of neurons
      within the horizontal limb of the diagonal band of Broca (hDBB) and investigated
      the role of excitatory amino acid mediated synaptic transmission in this region.
      Whole cell patch-clamp recordings were obtained from hDBB neurons in rat
      forebrain slices. The hDBB cells examined in this study display a morphological
      and electrophysiological profile that is consistent with the type B,
      noncholinergic cell type. Cable analysis reveals that hDBB neurons are
      electrotonically compact and may therefore function as efficient relays for
      transmission of inputs to other forebrain target sites. Application of agonists
      for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate, N
      methyl-D-aspartate (NMDA), and metabotropic receptors all evoke inward currents
      in hDBB neurons. Pharmacological analyses of synaptic events indicate that evoked
      excitatory postsynaptic currents (EPSC) are either mediated by non-NMDA receptors
      alone or a combination of non-NMDA and NMDA receptors. In some neurons, the
      metabotropic receptor agonist, 1-aminocyclopentane-trans-1, 3-dicarboxylic acid,
      reduced EPSC amplitude without altering postsynaptic input conductance, thus
      suggesting a presynaptic locus of action. The electrical and pharmacological
      properties described for hDBB neurons may be physiologically relevant for the
      effective transmission of excitatory synaptic inputs to sites that receive
      projections from the hDBB.

PMID- 9038823
TI  - Expression of the Na(+)-K(+)-2Cl- cotransporter BSC2 in the nervous system.
AB  - We used in situ hybridization and immunocytochemistry with polyclonal antibodies
      against the mouse bumetanide-sensitive Na(+)-K(+)-2Cl- cotransporter (mBSC2) to
      determine the location of this cotransporter in rat brain. Northern blots and in
      situ hybridization showed the presence of cotransporter mRNA in the brain, with
      an especially high level of expression in the choroid plexus (CP). Affinity
      purified anti-BSC2 antibody identified proteins of 145-155 kDa on Western blot
      analysis and immunoprecipitation of brain and CP membrane protein. Indirect
      immunofluorescence demonstrated that BSC2 protein is located on the apical
      surface of the CP and is heterogeneously distributed in cell bodies and dendrites
      of neurons in the central and peripheral nervous system. The apical localization
      of BSC2 in the CP was confirmed by 86Rb+ uptakes in primary cultures of CP cells
      grown on permeable filters and confocal immunofluorescence microscopy. The apical
      localization of the cotransporter in CP epithelium suggests a role for the
      cotransporter in cerebrospinal fluid K+ homeostasis. In neurons, the
      cotransporter may help regulate intracellular Cl- concentration and thereby
      affect neuronal response to gamma-aminobutyric acid.

PMID- 9038824
TI  - Glucocorticosteroids increase sodium transport in middle ear epithelium.
AB  - The effect of glucocorticosteroids on ion transport was investigated on a middle
      ear cell line with the short-circuit current (Isc) technique. Dexamethasone (DXM)
      produced a dose- and time-dependent increase in Isc. Concentration of half
      maximal stimulation was 2.68 x 10(-8) M. This effect was blunted by the
      glucocorticoid antagonist RU-38486 and was related to Na+ transport, as evidenced
      by the inhibition induced by 1) apical addition of the Na+ channel inhibitor
      benzamil (10(-6) M) or 2) substitution of Na+ with N-methylglucamine in the
      incubation medium. The increase in Na+ transport resulted from a primary
      modulation of apical Na+ entry, since 1) the Na(+)-K(+)-ATPase activity of
      cellular homogenates was not modified by corticosteroids and 2) the DXM-induced
      increase in the ouabain-sensitive uptake of 86Rb was blunted by benzamil.
      Ribonuclease protection assay revealed 1) a constitutive expression of the mRNA
      encoding the alpha-subunit of the epithelial Na+ channel and 2) that DXM
      increased the expression of this transcript. This increase was dose dependent and
      paralleled changes in transepithelial Na+ transport. This study suggests that a
      component of the beneficial effect of steroid therapy for the treatment of otitis
      media might be related to increased fluid clearance.

PMID- 9038825
TI  - Secondary regulatory volume increase conferred on Xenopus oocytes by expression
      of AE2 anion exchanger.
AB  - Xenopus oocytes lack volume regulation and Cl/anion-exchange (AE) activity but
      express endogenous Na+/H+ exchange (NHE). We postulated that expression in
      oocytes of heterologous anion exchangers might allow regulatory volume increase
      (RVI) via functional coupling with endogenous NHE. Expression of neither
      erythroid nor kidney isoforms of AE1 conferred any form of RVI. In contrast,
      although AE2 expression did not confer primary RVI, it did confer on oocytes
      secondary RVI, with a requirement for hypotonic swelling before hypertonic
      shrinkage. This secondary RVI required extracellular Cl- and Na+, was blocked by
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and amiloride, was bumetanide
      insensitive, and was blocked by prevention of intracellular alkalinization, all
      properties consistent with functional coupling of AE2-mediated Cl-/HCO3- exchange
      and endogenous NHE. RVI was unaffected by CO2-HCO3- or by partial oocyte Cl-
      depletion and was unrelated to the rate of oocyte shrinkage. Prior hypotonic
      swelling did not significantly alter subsequent hypertonic stimulation of AE2
      mediated 36Cl influx or efflux. We conclude that heterologous AE2 expression
      suffices to confer volume regulation on Xenopus oocytes that lack intrinsic
      volume-regulatory mechanisms.

PMID- 9038826
TI  - Reduced Mg2+ inhibition of Ca2+ release in muscle fibers of pigs susceptible to
      malignant hyperthermia.
AB  - The inhibitory effect of myoplasmic Mg2+ on Ca2+ release from the sarcoplasmic
      reticulum (SR) was examined in mechanically skinned skeletal muscle fibers from
      pigs of different ryanodine-receptor (RyR) genotypes. In fibers from pigs
      homozygous for the normal RyR allele, the free Mg2+ concentration ([Mg2+]) had to
      be lowered from the normal resting level of 1 to approximately 0.1 mM to induce
      Ca2+ release and a force response. Fibers from pigs heterozygous or homozygous
      for the RyR allele associated with malignant hyperthermia (MH) needed only a
      smaller reduction in free [Mg2+] to induce Ca2+ release (reduction to 0.1-0.2 and
      > or = 0.2 mM, respectively). Dantrolene (20 microM) counteracted the effect of
      this reduced Mg2+ inhibition in MH muscle. The response of muscle fiber bundles
      to the caffeine-halothane contracture test in the three genotypes correlated well
      with the responsiveness of single fibers to reduced [Mg2+]. Thus the abnormal
      responsiveness of MH muscle to various stimuli may largely result from the
      reduced ability of myoplasmic Mg2+ to inhibit Ca2+ release from the SR.

PMID- 9038827
TI  - Volume-sensitive chloride current in pigmented ciliary epithelial cells: role of
      phospholipases.
AB  - The whole cell recording technique was used to examine an outwardly rectifying
      chloride current activated by hypotonic shock in bovine pigmented ciliary
      epithelial (PCE) cells. Removal of internal and external Ca2+ did not affect the
      activation of these currents, but they were abolished by the phospholipase C
      inhibitor neomycin. The current was blocked by 5-nitro-2-(3
      phenylpropylamino)benzoic acid, 4-acetamido-4'-isothiocyanostilbene-2,2'
      disulfonic acid, and 4,4'-disothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a
      voltage-dependent manner, but tamoxifen, dideoxyforskolin, and quinidine did not
      affect it. This blocking profile differs from that of the volume-sensitive
      chloride channel in neighboring nonpigmented ciliary epithelial cells (Wu, J., J.
      J. Zhang, H. Koppel, and T. J. C. Jacob, J. Physiol, Lond. 491: 743-755, 1996),
      and this difference implies that the volume responses of the two cell types are
      mediated by different chloride channels (Jacob, T. J. C., and J. J. Zhang. J.
      Physiol. Lond. In press). Intracellular administration of guanosine 5'-O-(3
      thiotriphosphate) (GTP gamma S) to PCE cells induced a transient, time
      independent, outwardly rectifying chloride current that closely resembled the
      current activated by hypotonic shock. DIDS produced a voltage-dependent block of
      the GTP gamma S-activated current similar to the block of the hypotonically
      activated current. Intracellular neomycin completely prevented activation of this
      current as did incubation of the cells in calphostin C. and inhibitor of protein
      kinase C (PKC). Removal of Ca2+ did not affect activation of the current by GTP
      gamma S but extended the duration of the response. Inhibition of phospholipase A2
      (PLA2) with p-bromophenacyl bromide prevented the activation of the hypotonically
      induced current and also inhibited the current once activated by hypotonic
      solution. The findings imply that the hypotonic response in PCE cells is mediated
      by both phospholipase C (PLC) and PLA2. Both phospholipases generate arachidonic
      acid, and, in addition, the PLC pathway regulates the PLA2 pathway via a PKC
      dependent phosphorylation of PLA2.

PMID- 9038828
TI  - Association of Tyr phosphorylation of GTPase-activating protein with mitogenic
      action of serotonin.
AB  - We have previously shown that serotonin (5-HT) induces both hyperplasia and
      hypertrophy of pulmonary artery smooth muscle cells (SMC) but not of endothelial
      cells (EC) through its high-affinity uptake. The present studies demonstrate
      rapid enhancement by 5-HT of Tyr phosphorylation of proteins, including p120,
      which also occurs in SMC but not in EC. The p120 protein was identified as GTPase
      activating protein (GAP) by immunoprecipitation. Its phosphorylation occurred
      within minutes and preceded other events associated with 5-HT-induced
      mitogenesis. Tyr kinase (TK) and 5-HT uptake inhibitors and 8-bromoadenosine
      3',5'-cyclic monophosphate blocked both the 5-HT-induced DNA synthesis and Tyr
      phosphorylation of GAP. Vanadate elevated DNA synthesis and Tyr phosphorylation
      of GAP of both control and 5-HT-treated cells. 5-HT failed to alter Tyr
      phosphorylation of GAP in cellular homogenates, as opposed to intact cells. In
      the presence of 3-isobutyl-1-methylxanthine, 5-HT inhibited cellular growth,
      presumably through its action on 5-HT1A or 5-HT4 receptors and elevation of
      adenosine 3',5'-cyclic monophosphate, but this was not associated with an
      alteration of Tyr phosphorylation of GAP. Similarly, a 5-HT1 or 5-HT2 receptor
      agonist failed to stimulate Tyr phosphorylation or DNA synthesis of SMC.
      Stimulation of cellular proliferation and enlargement produced by 1 microM 5-HT
      were totally abolished by TK inhibitors that did not affect 5-HT uptake. These
      data indicate that Tyr phosphorylation of GAP may act as an intermediate signal
      in 5-HT-induced mitogenesis of SMC which requires cellular internalization of 5
      HT rather than its action on a membrane receptor.

PMID- 9038829
TI  - Functional properties of cultured endothelial cells derived from large
      microvessels of human brain.
AB  - This report describes the fractional separation of microvessels from human brain
      for establishment of segmentally derived endothelial cell (EC) cultures. The
      investigation comprised evaluation of media constituents and purity of the cell
      culture and focused on functional biochemical characterization of endothelium
      derived from large microvessels (EC) Cells contained endothelial marker factor
      VIII (von Willebrand antigen), secreted endothelin-1 (ET-1) and prostaglandins,
      and took up 86Rb+ as a measure of K+. Exogenous ET-1 stimulated
      phosphatidylinositol hydrolysis and K+ uptake; BQ-123 (selective ETA receptor
      antagonist) but not IRL-1038 or BQ-788 (selective ETB receptor antagonists)
      inhibited both. Ouabain (inhibitor of Na(+)-K(+)-ATPase) and bumetanide
      (inhibitor of Na(+)-K(+)-Cl- cotransport) reduced (74-80 and 20-40%,
      respectively) the ET-1-stimulated K+ uptake. Staurosporine [protein kinase C
      (PKC) inhibitor] selectively reduced Na(+)-K(+)-Cl- cotransport, whereas
      verapamil but not nifedipine (L-type voltage-dependent Ca2+ channel blockers)
      decreased Na(+)-K(+)-ATPase activity induced by ET-1. Phorbol 12-myristate 13
      acetate (PMA; activator of PKC) stimulated K+ uptake, which was only decreased
      with bumetanide. N-ethylisopropylamiloride (inhibitor of Na+/H+ exchange) reduced
      the ET-1-stimulated but not the PMA-induced K+ uptake. Results indicate that
      phosphatidylinositol hydrolysis and ion transport systems in large microvascular
      EC are stimulated by ET-1 through activation of ETA receptors. The findings also
      suggest that the ET-1-stimulated Na(+)-K(+)-ATPase activity, in contrast to Na(+)
      K(+)-Cl- cotransport, is not mediated by PKC. In addition, the data suggest a
      linkage between Na(+)-K(+)-ATPase activity and Na+/H+ exchange.

PMID- 9038830
TI  - Preferential potentiation by hypotonic cell swelling of muscarinic cation current
      in guinea pig ileum.
AB  - The effects of hypotonic cell swelling (HCS) on muscarinic receptor-activated
      cationic current in guinea pig ileal smooth muscle were investigated by the whole
      cell patch-clamp technique. With nystatin-perforated recording, reduced external
      tonicity from 312 to 262 mosM caused cell swelling but hardly affected the
      membrane currents activated by depolarization, such as outward-rectifying K and
      voltage-dependent Ca currents. In contrast, the inward current evoked by
      carbachol at -60 mV was greatly increased (approximately 50%) by the same extent
      of hypotonicity. This effect is likely to occur through potentiation of
      nonselective cation channels coupled to the muscarinic receptor (mNSCCs) and
      probably does not involve elevated intracellular Ca2+ concentration ([Ca2+]i),
      since neither removal of external Ca2+ nor [Ca2+]i buffering with 10 mM 1,2-bis
      (2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid significantly affected the
      results. Furthermore, the time course and degree of this potentiation closely
      matched those of video-microscopically monitored HCS. These results support the
      view that mechanosensitive modulation may be a powerful mechanism to regulate
      mNSCCs activity in gut smooth muscle, together with membrane potential and
      [Ca2+]i.

PMID- 9038831
TI  - Effects of F-actin stabilization or disassembly on epithelial Cl- secretion and
      Na-K-2Cl cotransport.
AB  - Previous studies showed that cAMP-dependent transepithelial Cl- secretion of the
      intestinal cell line T84 is reduced by the F-actin stabilizer phalloidin, an
      effect in part attributable to inhibition of basolateral Na-K-2Cl cotransport.
      However, secretory responses are preserved in cells treated with the
      microfilament disrupter cytochalasin D. We explored the effects of cytochalasin D
      and two novel compounds derived from marine sponges on the Cl- secretory
      apparatus of T84 cells. Jasplakinolide (which stabilizes F-actin inhibited cAMP
      dependent secretion and Na-K-2Cl cotransport. Latrunculin A (which sequesters G
      actin monomers) profoundly altered the distribution of F-actin and reduced basal
      transepithelial resistance with minimal effect on secretion. Cytochalasin D, but
      not latrunculin A, activated Na-K-2Cl cotransport. The results provide further
      evidence that vectorial ion transport is influenced by the cytoskeleton and
      support a model in which disassembly of F-actin by specific pharmacological means
      or in response to secretory agonists favors activation of Na-K-2Cl cotransport.

PMID- 9038832
TI  - Lacrimal gland PKC isoforms are differentially involved in agonist-induced
      protein secretion.
AB  - In the present study, we have synthesized and N-myristoylated peptides derived
      from the pseudosubstrate sequences of protein kinase C (PKC)-alpha, -delta, and 
      epsilon [Myr-PKC-alpha-(15-28), Myr-PKC-delta-(142-153), and Myr-PKC-epsilon-(149
      164)], three isoforms present in rat lacrimal gland, and a peptide derived from
      the sequence of the endogenous inhibitor of protein kinase A [Myr-PKI-(17-25)].
      Lacrimal gland acini were preincubated for 60 min with the myristoylated peptides
      (10(-10) to 3 x 10(-7) M), then protein secretion was stimulated with a phorbol
      ester, phorbol 12,13-dibutyrate (10(-6) M); vasoactive intestinal peptide (10(-8)
      M); a cholinergic agonist, carbachol (10(-5) M); or an alpha 1-adrenergic
      agonist, phenylephrine (10(-4) M), for 20 min. In intact lacrimal gland acini,
      Myr-PKC-alpha-(15-28) inhibited phorbol 12,13-dibutyrate-induced protein
      secretion. This effect was not reproduced by the acetylated peptide or by the
      myristoylated PKI, which inhibited vasoactive intestinal peptide-induced protein
      secretion, a response mediated by protein kinase A. Carbachol-induced protein
      secretion was inhibited by all three peptides. In contrast, phenylephrine-induced
      protein secretion was inhibited only by Myr-PKC-epsilon-(149-164), whereas Myr
      PKC-alpha-(15-28) and Myr-PKC-delta-(142-153) had a stimulatory effect. None of
      these myristoylated peptides affected the calcium increase evoked by cholinergic
      or alpha 1-adrenergic agonists. We concluded that phorbol ester- and receptor
      induced protein secretion involve different PKC isoforms in lacrimal gland.

PMID- 9038833
TI  - Cloning and induction by low NaCl intake of avian intestine Na+ channel subunits.
AB  - The alpha-subunit of the highly Na(+)-selective amiloride-blockable channel
      (ENaC) was cloned from chicken lower intestine. The deduced amino acid sequence
      of the avian clone exhibits -60% identity to the previously cloned mammalian and
      amphibian alpha-subunits. It also maintains the same hydropathy profile and
      structural motifs. These include two transmembrane domains separated by a large
      extracellular loop, four extracellular N-glycosylation sites, a cysteine-rich box
      in the extracellular domain, and a proline-rich stretch at the carboxy terminus.
      Xenopus oocytes injected with cRNA transcribed from this clone express a small
      amiloride-blockable Na+ conductance. Degenerate primers have been used to amplify
      two other related products. Sequence homology indicates that one of them is the
      beta-subunit, whereas the other appears to represent a closely related but
      different transcript. Regulation of the mRNA corresponding to these clones was
      examined in chickens fed normal and low-NaCl rations. The low-salt diet evoked an
      approximately fourfold increase in the abundance of mRNA coding for the alpha
      subunit, presumably through an increase in plasma aldosterone. The beta- and
      "beta-like" transcripts were even more strongly affected. The current data
      provide additional information on sequence conservation in the growing ENaC
      family and demonstrate that the avian intestine channel is strongly induced by
      varying NaCl intake.

PMID- 9038834
TI  - Vanadate oxidation activates contraction in skinned smooth muscle without myosin
      light chain phosphorylation.
AB  - Phosphorylation of the myosin regulatory light chain (LC20-P1) is the major route
      of smooth muscle activation. However, after prior exposure to vanadate,
      permeabilized guinea pig taenia coli smooth muscle contracts in the absence of
      LC20-P1. We characterized the vanadate-induced contraction and investigated the
      mechanism of this novel activation pathway. Addition of vanadate to a control
      contracture (6.6 microM Ca2+) inhibits force (effective dose for 50% response was
      approximately 100 microM). In contrast, preincubation with high concentrations of
      vanadate (threshold at 1-2 mM) elicited a contraction on subsequent transfer of
      the fiber to a vanadate-free, Ca(2+)-free solution. Maximum isometric force of
      approximately 60% of control was obtained in fibers preincubated in 4 mM vanadate
      for 10 min. Addition of Ca2+ to a vanadate-induced contracture increased force,
      but the total force never exceeded the initial control. After maximal
      thiophosphorylation of LC20 with adenosine 5'-O-(3-thiotriphosphate), treatment
      with vanadate did not increase force. Unloaded shortening velocity (Vmax) was
      similar in Ca2+ and vanadate contractures and was additive. After
      thiophosphorylation, preincubation in vanadate had no effect on Vmax, suggesting
      that vanadate affected the number of activated bridges and not cycle rate.
      Vanadate mechanisms likely involve oxidation, since preincubation with 4 mM
      vanadate and 25 mM dithiothreitol (DTT) did not produce force. DTT could reverse
      a vanadate-induced contracture in 30-60 min. Subsequently, fibers demonstrated
      control contraction/relaxation cycles. Thus vanadate treatment did not cause
      irreversible damage, such as the extraction of proteins. Potential oxidation
      sites are proteins at 17 kDa and between 30 and 40 kDa, which were not alkylated
      by N-ethylmaleimide if they were treated in the presence of vanadate or in the
      rigor state. Vanadate-induced contractures are likely mediated by a reversible
      oxidation that activates cross bridges similarly to that of LC20-Pi and may play
      an important role in oxidant injury.

PMID- 9038836
TI  - Protection from apoptosis in human neutrophils is determined by the surface of
      adhesion.
AB  - Recent work suggests that various neutrophil agonists affect the rate of
      apoptosis in these cells. On the basis of these observations, we hypothesized
      that signals triggered in neutrophils via their adhesion receptors might also
      modify their life span. This hypothesis has been tested using human neutrophils
      adherent to tissue culture plastic, either untreated or coated with extracellular
      matrix (ECM) proteins or with monolayers of human umbilical vein endothelial
      cells. To detect and quantitate apoptotic changes in adherent cells, we developed
      a microtiter plate assay using a cell-permeable DNA-binding fluorescent dye,
      Hoechst 33342. Use of this assay demonstrated that 1) the number of apoptotic
      cells among neutrophils adherent to plastic after 6-20 h of incubation was
      significantly lower than that among neutrophils adherent to the ECM proteins
      fibronectin or laminin; 2) adhesion to interleukin-1-activated endothelial cells
      delayed apoptosis, whereas adhesion to nonactivated endothelium accelerated
      neutrophil death; and 3) monoclonal antibodies directed against intercellular
      adhesion molecule 1 or against the common beta 2-chain of the leukocyte integrins
      abolished the protective effect of interleukin-1-activated endothelial cells on
      apoptosis of adherent neutrophils. These results suggest that the life span of
      adherent neutrophils. depends on the activating signals triggered by the surface
      of adhesion.

PMID- 9038835
TI  - Pathways of hepatic oxalate synthesis and their regulation.
AB  - Important features of hepatic oxalate synthesis remain uncertain despite its
      clinical significance. To clarify the terminal steps of the biosynthetic pathway
      and their modulation, we have examined oxalate and glyoxylate synthesis in vitro
      using isolated guinea pig peroxisomes and purified lactate dehydrogenase (LDH).
      Glycolate was rapidly oxidized to glyoxylate by isolated peroxisomes followed by
      a slower conversion of glyoxylate to oxalate. The glycolate oxidase (GO)
      catalyzed conversion of glyoxylate to oxalate was strongly inhibited by
      physiological concentrations of glycolate and lactate. In contrast, the LDH
      catalyzed conversion of glyoxylate to oxalate was only marginally affected by
      physiological concentrations of lactate and unaffected by physiological glycolate
      concentrations. This inhibition pattern suggests that LDH, not GO, catalyzes this
      conversion in vivo. Alanine inhibited oxalate synthesis by converting the bulk of
      the glyoxylate to glycine. On exposure to high alanine concentrations, however,
      inhibition was not complete and peroxisomes were able to convert sufficient
      glycolate to oxalate to account for daily endogenous oxalate production. NADH was
      a potent inhibitor of oxalate production by LDH by increasing glycolate formation
      from glyoxylate. Glycine was an ineffective source of glyoxylate, and an alkaline
      pH, a high-glycine concentration, and a prolonged incubation time were required
      to obtain a detectable synthesis. These results suggest that oxalate synthesis
      will be modulated by the metabolic state of the liver and resultant changes in
      NADH, lactate, and alanine levels.

PMID- 9038837
TI  - Effect of the organic Ca2+ channel blocker D-600 on sarcoplasmic reticulum Ca2+
      uptake in skeletal muscle.
AB  - Experiments were undertaken to study the possibility that the calcium channel
      blocker D-600 (gallopamil), which penetrates into muscle cells (20), facilitates
      excitation-contraction coupling in skeletal muscle (7) by a direct effect on the
      sarcoplasmic reticulum (SR). The effects of D-600 were studied on single phasic
      muscle fibers, either intact or split open. D-600 potentiated twitches in intact
      fibers at concentrations lower than those reported in whole muscles. In split
      fibers, the force produced by caffeine-induced Ca2+ release from the SR was
      reversibly inhibited by 5 microM D-600, when added to the Ca2+ loading solution.
      This inhibitory effect was inversely related to temperature, and it was dose
      dependent. When D-600 was added after Ca2+ loading and before caffeine exposure,
      or during the caffeine exposure itself, it did not inhibit Ca2+ release, but
      rather increased the development of force. We conclude that, apart from the
      blocking effect that D-600 may have on the voltage sensor, the drug penetrates
      into the myoplasm and affects excitation-contraction coupling by inhibiting the
      SR Ca2+ pump. This may be the consequence of a conformational change in the
      transmembrane Ca2+ binding domain of the ATPase.

PMID- 9038838
TI  - Isovolumetric regulation of C6 rat glioma cells in hyperosmotic media.
AB  - Volume regulation of C6 glioma cells was studied in response to a gradual
      increase of extracellular osmolality from 300 to 440 mosmol/kgH2O at 37 degrees
      C. Maintenance of cell size depended on the rate of osmolality increase (CR): at
      CR of 3 mosmol.kg-1.min-1, cell volume was kept constant, whereas it decreased
      progressively at CR of 6 or 9 mosmol.kg-1.min-1. The ability of C6 cells to
      maintain their volume is termed isovolumetric regulation (IVR). Reducing
      temperature to 22 degrees C inhibited IVR significantly. Also, bumetanide and
      ouabain blocked the regulation, while 5-(N,N-dimethyl)amiloride (DMA) did not
      affect IVR: Extracellular acidification rate (EAR) was studied by
      microphysiometry. EAR gradually decreased in the presence and increased in the
      absence of IVR. Experiments with DMA show that these changes in EAR were related
      to the activity of the Na+/H+ exchanger. It was stimulated by cell shrinkage but
      not by hyperosmolality itself. Our data demonstrate that C6 glioma cells are able
      to prevent volume decrease at a low rate of elevation of external osmolality and
      at 37 degrees C. This process requires electrolyte uptake by the Na(+)-K(+)-2Cl
      cotransporter and Na+/K+ pump.

PMID- 9038839
TI  - A redox O2 sensor modulates the SR Ca2+ countercurrent through voltage- and
      Ca(2+)-dependent Cl- channels.
AB  - The activity of a relatively small Cl- (SCl) channel in the sarcoplasmic
      reticulum (SR) vesicles of rabbit skeletal muscle was preserved following their
      reconstitution into lipid bilayer. Reducing PO2 from approximately 150 to < 1
      Torr in the cis-side (cytosolic) reversibly inhibited the channel activity within
      2 min. The modulatory effects, deduced from reduction in Cl- current levels and
      in kinetic parameters of channel activation, in normoxic (PO2 approximately 150
      Torr) and hypoxic (low PO2 < 1 Torr) solutions were mimicked by oxidizing and
      reducing agents, respectively. Cl- current transitions to the main open
      conductance state were increased by 100 microM of the specific sulfhydryl (SH)
      oxidizing agent 4,4'-dithiodipyridine and inhibited by the SH-reducing agent
      glutathione (GSH) with a Hill coefficient of 8 and inhibition constant of
      approximately 3.1 mM. The inhibitory effects of 5 mM [GSH]cis were prevented by
      prior addition of 1 mM iodoacetamide, an alkylating agent, to the cytosolic side
      of the channel. These findings suggest that an SH-dependent mechanism (redox
      couple, e.g., reduced/oxidized glutathione) could be involved in the gating of
      the SCl channel in such a way that SH oxidation (GSSH) favors the open state of
      the channel, and SH reduction (GSH), which mimics the inhibitory action of low
      PO2, favors the closed state.

PMID- 9038840
TI  - Electrical properties of diaphragm and EDL muscles during the life of dystrophic
      mice.
AB  - The membrane electrical properties of diaphragm and extensor digitorum longus
      (EDL) muscle fibers of dystrophic mdx and control mice from 4 wk to 14-19 mo of
      age were recorded with the intracellular microelectrode technique. Up to 8 wk of
      age, the diaphragm and EDL muscles did not differ between the two strains. From 8
      up to 20 wk, the mdx diaphragm fibers showed a higher membrane resistance (Rm),
      which was due to significantly lower values of resting chloride conductance (GCl)
      and an overexcitability with respect to age-matched controls. Oppositely, the mdx
      EDL muscle fibers had significantly lower Rm and higher GCl values than age
      related controls at 8, 10, and 13 wk, along with a decreased membrane
      excitability. These differences were no longer detectable at 20 wk. The diaphragm
      and EDL muscles from 14- to 19-mo-old controls showed a decrease of GCl and an
      increase of potassium conductance with respect to adult animals. In aged mdx
      animals, these changes were very dramatic in diaphragm fibers, whereas no
      differences, with respect to adults, were found in the EDL muscle. Thus GCl is an
      index of the dystrophic condition of mdx muscles. In the degenerating diaphragm,
      the impairment of GCl can account for some of the pathological features of the
      muscle. In the EDL muscle, the changes of GCl can follow the high regenerative
      potential of the hindlimb muscles of the mdx phenotype.

PMID- 9038841
TI  - Muscarinic activation and calcium permeation of nonselective cation currents in
      airway myocytes.
AB  - We examined the activation and Ca2+ permeation of nonselective cation channels in
      voltage-clamped (nystatin), fura 2-loaded equine tracheal myocytes at 35 degrees
      C. Methacholine (50 microM) induced a biphasic increase in intracellular Ca2+
      concentration ([Ca2+]i) and a biphasic inward current consisting of a large,
      rapidly inactivating Ca(2+)-activated Cl current [ICl(Ca)] and a smaller,
      sustained nonselective cation current (Icat) ICl(Ca) but not Icat was activated
      by caffeine. Neither Icat nor the sustained rise in [Ca2+]i was blocked by
      nisoldipine, whereas both were rapidly blocked by Ni2+; Icat was determined to be
      Ca2+ permeant, since 1) a sustained elevation of [Ca2+]i occurred when Icat was
      activated, and blockade of Icat produced a rapid decline in [Ca2+]i; 2)
      increasing extracellular Ca2+ during Icat increased [Ca2+]i; 3) 110 mM
      extracellular Ca2+ shifted the reversal potential of Icat to 12 mV (Ca(2+)-to-Cs+
      permeability ratio = 3.6); and 4) instantaneous voltage-clamp steps to negative
      potentials during Icat increased the current and [Ca2+]i, whereas depolarizing
      steps decreased the current and [Ca2+]i. The fraction of Icat carried by Ca2+
      under physiological conditions was estimated to be 14% at -60 mV.

PMID- 9038843
TI  - Similar sequence in E. coli.

PMID- 9038842
TI  - Reinterpretation of the RACTK1 K+ channel.
AB  - The RACTK1 cDNA cloned from rabbit kidney cortical collecting duct cells was
      associated with inwardly rectifying pH-regulated K+ channel activity (M. Suzuki,
      K. Takahashi, M. [keda, H Hayakawa, A. Ogawa, Y. Kawaguchi, and O. Sakai. Nature
      Lond. 367: 642-645, 1994). The deduced amino acid sequence of the encoded novel
      polypeptide lacked the signature sequence of a K(+)-selective pore region but
      predicted a topography suggestive of the inward rectifier K+ channel family. In
      subsequent articles a RACTK1 epitope was immunolocalized to the apical surface of
      kidney collecting duct and to arteriolar smooth muscle [M. Suzuki, T. Takigawa,
      K. Kimura, C. Koseki, and M. Imai. Am. J. Physiol. 269 (Cell Physiol, 38): C496
      C503, 1995], and apamin-sensitive K+ currents displaying Ca(2+)-dependent and
      voltage-independent activation accompanied stable heterologous overexpression of
      RACTK1 [M. Suzuki, M. Murata, M. Ikeda, T. Miyoshi, and M. Imai. Am. J. Physiol.
      270 (Cell Physiol, 39): C964-C968, 1996]. We now report that the "RACTK1" open
      reading frame is a frame-shifted translation of the antisense strand of an
      Escherichia coli gene member of a coenzyme A transferase gene family. "RACTK1"
      mRNA was absent from tissues free of E. coli contamination, and the "RACTK1" gene
      was undetectable in Southern blots of human and rabbit genomic DNA. We conclude
      that the immunostaining patterns and Ca(2+)-activated K+ channel activity
      heretofore attributed to RACTK1 must be otherwise explained.

PMID- 9038844
TI  - Effect of magnesium on parathyroid cells: evidence for two sensing receptors or
      two intracellular pathways?
AB  - It currently remains controversial as to the intracellular mechanisms coupled to
      the inhibition of parathyroid hormone (PTH) secretion that are modulated by
      extracellular divalent cations. To study mechanisms responsible for regulation of
      PTH release by cations, we investigated the effect of Mg2+ on cytosolic Ca2+
      levels ([Ca2+]i) and PTH secretion in single isolated bovine parathyroid cells.
      Addition of 9.0 mM Mg2+ evoked a spike of [Ca2+]i in approximately 80% of cells
      in the presence of extracellular Ca2+. Mg2+ decreased steady-state [Ca2+]i, which
      represented inhibition of influx of extracellular Ca2+ in 13-78% of cells. The
      percentage of cells that had a decline in steady-state [Ca2+]i after exposure to
      Mg2+ was dependent on the extracellular Ca2+ concentration. The effect of Mg2+ on
      intracellular Ca2+ response was dose dependent. Extracellular Mg2+ inhibited PTH
      secretion in cells that showed decline in steady-state [Ca2+]i, although cells
      that showed a spike after addition of Mg2+ secreted more PTH than cells that did
      not show a spike. The spike of [Ca2+]i and decline in steady-state [Ca2+]i that
      occur in response to extracellular Mg2+ may be caused independently by two
      distinct mechanisms that differentially regulate secretion of PTH.

PMID- 9038846
TI  - Effects of dihydropyridines on aldosterone secretion in adrenal capsule
      preparations from pregnant rats.
AB  - The primary aim of this study was to determine when sensitivity in the
      aldosterone response to extracellular potassium (K+) decreases during pregnancy.
      Second, it tested the hypothesis that calcium channel alterations occur in the
      adrenal cortex during pregnancy. The decreased sensitivity to K+, observed at 22
      days of gestation, was not evident at 15 days and between 18 and 36 h postpartum.
      Increases in extracellular calcium concentration heightened sensitivity to K+ in
      adrenal capsule preparations derived from nonpregnant rats but had no effect in
      pregnant animals. The influence of nifedipine and BAY K 8644 (blocker and
      activator, respectively, of voltage-operated calcium channels) on the aldosterone
      response to K+ and to adrenocorticotropic hormone (ACTH) was studied. Sensitivity
      to K+ in nonpregnant rats decreased in the presence of nifedipine and became
      similar to that in pregnant rats. Responses to ACTH were not affected by
      nifedipine. BAY K 8644 produced a larger increase in sensitivity in adrenal
      capsule preparations from pregnant than from nonpregnant rats, leading to
      superposition of the two dose-response curves to K+. These results indicate that
      voltage-operated calcium channels involved in aldosterone secretion are
      functionally impaired during pregnancy.

PMID- 9038847
TI  - Retinol is specifically required during midgestation for neonatal survival.
AB  - Previous work has demonstrated that vitamin A-deficient, retinoic acid
      supplemented pregnant rats cannot complete gestation without the administration
      of retinol. As little as 2 micrograms administered on day 10 of gestation is
      sufficient to prevent the characteristic fetal resorption that begins at day 15
      of gestation. This single dose of retinol supports continued development through
      day 20 of gestation. However, if gestation is allowed to proceed to parturition,
      the newborn pups die within a few minutes of being severed from the umbilical
      cord. The pups are born with a pink and healthy skin tone, but within seconds of
      umbilical separation, they begin to gasp for air, become cyanotic in appearance,
      and die within several minutes from an apparent inability to obtain oxygen.
      Histological examination of these neonates demonstrates delayed pulmonary
      development. Branching and scalloping of ducts and saccule and subsaccule
      formation are decreased. This phenotype is consistent with that observed in
      respiratory distress syndrome seen in some premature human infants.

PMID- 9038845
TI  - Effect of in vivo injection of cholera and pertussis toxin on glucose transport
      in rat skeletal muscle.
AB  - Cholera toxin (CTX) and pertussis toxin (PTX) were examined for their ability to
      inhibit glucose transport in perfused skeletal muscle. Twenty-five hours after an
      intravenous injection of CTX, basal transport was decreased approximately 30%,
      and insulin- and contraction-stimulated transport was reduced at least 86 and
      49%, respectively, in both the soleus and red and white gastrocnemius muscles. In
      contrast, PTX treatment was much less efficient. Impairment of glucose transport
      appeared to develop 10-15 h after CTX administration, which coincided with
      development of hyperglycemia despite hyperinsulinimia, increased plasma free
      fatty acid levels, increased adenosine 3',5'-cyclic monophosphate (cAMP)
      concentrations in muscle, but no difference in plasma catecholamines. Twenty-five
      hours after CTX treatment, GLUT-4 protein in both soleus and red gastrocnemius
      muscles was decreased, whereas no change in GLUT-1 protein content was found. In
      contrast, GLUT-4 mRNA was unchanged, but transcripts for GLUT-1 were increased >
      or = 150% in all three muscles from CTX-treated rats. The findings suggest that
      CTX via increased cAMP impairs basal as well as insulin- and contraction
      stimulated muscle glucose transport, at least in part from a decrease in
      intramuscular GLUT-4 protein.

PMID- 9038848
TI  - Effects of bis(maltolato)oxovanadium(IV) are distinct from food restriction in
      STZ-diabetic rats.
AB  - In association with the insulin-mimetic properties, vanadium and related
      compounds have been shown to normalize hyperphagia associated with diabetes
      mellitus. The objective of this study was to clarify the effects of an organic
      vanadium compound, bis(maltolato)oxovanadium(IV) (BMOV), vs. food restriction on
      the metabolic abnormalities that occur in diabetes. BMOV was administered daily
      in drinking water to streptozotocin (STZ)-diabetic rats for 6 wk. Pair-fed groups
      were fed based on the intake for their respective counterparts from the previous
      day. Plasma parameters were measured weekly after a carefully controlled 5-h
      fasting period. BMOV reduced plasma glucose (diabetic = 31.2 +/- 1.9, diabetic
      treated = 10.2 +/- 1.8, and diabetic pair fed = 34.2 +/- 1.1 mM), triglyceride,
      and cholesterol levels to normal without a concomitant increase in plasma insulin
      levels. There was no body weight gain in the diabetic pair-fed group compared
      with all other groups. BMOV but not pair feeding was effective in preventing the
      decreased cardiac function observed in STZ-diabetic rats. These data suggest that
      the glucose-lowering properties of BMOV are independent of the effects of dietary
      restriction and reinforce the efficacy of BMOV as an effective antihyperglycemic
      agent.

PMID- 9038849
TI  - Maintaining muscle protein anabolism after a metabolic stress: role of dextrose
      vs. amino acid availability.
AB  - The effect of chronic hypocaloric parenteral infusions of amino acids (AA) vs.
      dextrose (D) on protein homeostasis after a generalized metabolic stress was
      examined. Multicatheterized mongrel dogs were metabolically challenged by a 4-day
      fast and then administered a 4-day intravenous infusion of saline (S, n = 8), D
      (n = 8), or isocaloric AA (n = 7). Although nitrogen balance (g.kg.1.day-1) was
      similarly negative with S (-0.37 +/- 0.05), D (-0.28 +/- 0.03), and AA (-0.37 +/-
      0.04) during the fasting period, it was less negative (P < or = 0.05) with AA (
      0.06 +/- 0.04) than with D (-0.20 +/- 0.03) or S (-0.23 +/- 0.04) during nutrient
      infusion. AA resulted in net hindlimb uptake and D in net hindlimb release of
      essential AA (570 +/- 261 vs. -248 +/- 59 nmol.kg-1.min-1). Whereas S and D
      infusions led to net hindlimb muscle protein loss (-37 +/- 24 and -89 +/- 33
      micrograms.kg-1.min-1, respectively, P < or = 0.05 vs. AA), parenteral AA
      resulted in net deposition (169 +/- 62 micrograms.kg-1.min-1) as measured using L
      [ring-2H5]phenylalanine. Thus hypocaloric parenteral D infusion after a metabolic
      stress does not favor nitrogen conservation, because net whole body nitrogen
      loss, skeletal muscle protein catabolism, and hindlimb AA release were not
      blunted compared with S infusion. Conversely, hypocaloric AA infusion preserves
      whole body and muscle protein stores.

PMID- 9038850
TI  - Skeletal muscle myosin heavy-chain synthesis rate in healthy humans.
AB  - Mixed muscle protein synthetic rate has been measured in humans. These
      measurements represent the average of synthetic rates of all muscle proteins with
      variable rates. We determined to what extent the synthesis rate of mixed muscle
      protein in humans reflects that of myosin heavy chain (MHC), the main contractile
      protein responsible for the conversion of ATP to mechanical energy as muscle
      contraction. Fractional synthetic rates of MHC and mixed muscle protein were
      measured from the increment of [13C]leucine in these proteins in vastus lateralis
      biopsy samples taken at 5 and 10 h during a primed continuous infusion of L-[1
      13C]leucine in 10 young healthy subjects. Calculations were done by use of plasma
      [13C]ketoisocaproate (KIC) and muscle tissue fluid [13C]leucine as surrogate
      measures of leucyl-tRNA. Fractional synthetic rate of MHC with plasma KIC (0.0299
      +/- 0.0043%/h) and tissue fluid leucine (0.0443 +/- 0.0056%/h) were only 72 +/-
      3% of that of mixed muscle protein (0.0408 +/- 0.0032 and 0.0603 +/- 0.0059%/h,
      respectively, with KIC and tissue fluid leucine). Contribution of MHC (7 +/- 1
      mg.kg-1.h-1) to synthetic rates of whole body mixed muscle protein (36 +/- 5
      mg.kg-1.h-1) and whole body protein (127 +/- 4 mg.kg-1.h-1) is only 18 +/- 1 and
      5 +/- 1%, respectively. This relatively low contribution of MHC to whole body and
      mixed muscle protein synthesis warrants direct measurement of synthesis rate of
      MHC in conditions involving abnormalities of muscle contractile function.

PMID- 9038851
TI  - Use of labeling pattern of liver glutamate to calculate rates of citric acid
      cycle and gluconeogenesis.
AB  - The use of the labeling pattern of hepatic glutamate during infusion of L-[3-13C]
      or [3-14C]lactate to calculate rates of citric acid cycle activity and
      gluconeogenesis has been proposed. We tested the validity of this approach by
      perfusing isolated rat livers (48 h starved) with pyruvate and lactate (10%
      enriched with [3-13C]lactate) without (control) or with infusion of glucagon (to
      inhibit pyruvate kinase), mercaptopicolinate (to inhibit phosphoenolpyruvate
      carboxykinase), or dichloroacetate (to stimulate pyruvate dehydrogenase).
      Compared with control experiments, glucagon increased glucose output (P < 0.05)
      and decreased the calculated flux through pyruvate kinase (P < 0.05).
      Mercaptopicolinate almost totally suppressed glucose production and dramatically
      reduced the calculated gluconeogenic rate and flux through phosphoenolpyruvate
      carboxykinase (P < 0.001). Dichloroacetate moderately increased the calculated
      flux through pyruvate dehydrogenase (P < 0.05). In experiments with perfused
      livers from fed rats, the calculated gluconeogenic rate and flux through
      phosphoenolpyruvate carboxykinase were very low compared with control experiments
      (P < 0.001), whereas the pyruvate dehydrogenase flux was increased (P < 0.05).
      Therefore, the expected modifications of the citric acid cycle activity and
      gluconeogenic rate were clearly detected using the labeling pattern of glutamate
      to calculate these metabolic rates. Except for the perfusions with
      mercaptopicolinate, the dilution by isotopic exchange in the oxaloacetate pool
      calculated from the model agreed with the actual dilution of enrichment between
      liver pyruvate and phosphoenolpyruvate. The present results support the validity
      of this approach to trace liver metabolism.

PMID- 9038852
TI  - Metabolic adaptation to protein restriction in insulin-dependent diabetes
      mellitus.
AB  - Eight normal subjects, four subjects with intensively treated insulin-dependent
      diabetes mellitus (IDDM), and six subjects with conventionally treated IDDM
      consumed a test meal of 0.5 g protein and 10 kcal per kg body weight, first while
      adapted to a conventional diet high in protein, and then again after 5 days of
      dietary protein restriction. Metabolic N balance (N consumed minus urea
      production) and net protein utilization were measured over the 9 h after
      consumption of the test meal, as was recovery in urea of 15N from a tracer dose
      of [15N]alanine included in each test meal. After the first test meal, N balance
      and net protein utilization were similar and close to zero for all groups. After
      the second test meal, N balance and net protein utilization became positive for
      all groups (P < 0.05) but significantly less so (P < 0.05) for the conventionally
      treated than for the normal and intensively treated diabetic subjects. 15N
      recovery in urea was reduced for all groups after the second test meal (P < 0.05)
      but probably less effectively (P < 0.09) for the conventionally treated diabetic
      subjects. Metabolic adaptation to protein restriction may be less effective than
      normal in conventionally treated IDDM.

PMID- 9038853
TI  - Separate and joint effects of arginine and glucose on ovine fetal insulin
      secretion.
AB  - To determine separate and joint effects of increases (delta) in fetal plasma
      concentrations of arginine (Af) and glucose (Gf) on fetal insulin (If) secretion
      (delta If), 15 late-gestation fetal sheep were given 5-min arginine bolus
      infusions (40, 86, 144, 201, and 402 mumol/kg estimated fetal wt) at 90 min of
      120 min steady-state glucose clamps (basal Gf, basal + 0.6 mM Gf, and basal + 1.1
      mM Gr), producing absolute and percent increases above basal Af of 25.8 +/- 1.3
      microM (+33%), 50.9 +/- 6.3 microM (+66%), 83.8 +/- 7.1 microM (+108%), 122.1 +/-
      9.4 microM (+156%), and 302.2 +/- 28.2 microM (+386%), respectively. Acute
      hyperglycemia alone produced an increase above basal If of 9 +/- I microU/ml
      (+80%) and 19 +/- 2 microU/ml (+170%) after basal + 0.6 mM Gf and basal + 1.1 mM
      Gf, respectively. Increasing values of delta Af showed separate but lesser
      effects on delta If, which were significant only at very high values of Af (>
      100% above mean normal Af) unless marked hyperglycemia (1.5- to 2-fold normal)
      was also present, demonstrating joint effects of delta Af and delta Gf on delta
      If according to a best-fit inverse polynomial response surface. We conclude that
      physiological increases in Af at normal glucose concentrations are not a potent
      stimulus to insulin secretion in fetal sheep.

PMID- 9038854
TI  - Effects and metabolism of fumarate in the perfused rat heart. A 13C mass
      isotopomer study.
AB  - The cardioprotective effects of fumarate have been linked to its metabolism to
      succinate through both oxidative and reductive pathways. To date, the relative
      contribution of these pathways is a subject of controversy. To address this
      question, we designed a protocol with 13C substrates and took advantage of 13C
      isotopomer analysis by gas chromatography-mass spectrometry. Rat hearts were
      perfused with 11 mM glucose, 1 mM lactate, 0.2 mM pyruvate, 0.2 mM [1
      13C]octanoate, and 0.04 or 0.4 mM [U-13C4]fumarate. On reoxygenation after 40 min
      of severe hypoxia, hearts perfused with 0.4 mM fumarate showed a better recovery
      of contractile function and released less lactate dehydrogenase (an index of
      cellular necrosis) than those perfused with 0.04 mM fumarate. The 13C data showed
      that, in hypoxic hearts, fumarate conversion to succinate occurred only through
      reduction, although it accounted for only 16% of total succinate release. Most of
      the succinate was formed through the oxidation of alpha-ketoglutarate or its
      precursors (50 +/- 5%) and by another yet-unidentified pathway (34 +/- 4%). These
      data show that, in a model of hypoxia-reoxygenation, the cardioprotective effects
      of fumarate were associated with its predominant metabolism to succinate through
      the reductive pathway.

PMID- 9038855
TI  - Urinary biotin analogs increase in humans during chronic supplementation: the
      analogs are biotin metabolites.
AB  - In human subjects, the metabolic origins of bisnorbiotin and biotin sulfoxide
      were determined by measuring the urinary excretion of each after chronic
      administration of large oral doses of biotin. For 2 wk, 14 adult volunteers
      consumed 1,200 micrograms of biotin per day, an amount approximately 20 times the
      daily dietary intake. With the use of a high-performance liquid
      chromatography/avidin-binding assay in untimed urine samples obtained before the
      first dose of biotin and after the 14th dose, concentrations of biotin,
      bisnorbiotin, and biotin sulfoxide were measured. Excretion was expressed as
      concentration ratios to urinary creatinine. Bisnorbiotin and biotin sulfoxide
      excretion increased 85-fold (P < 0.0001) and 114-fold (P < 0.0001), respectively.
      The molar percentages of bisnorbiotin and biotin sulfoxide decreased from 28 to
      14% (P = 0.006) and from 9 to 5% (P = 0.017), respectively. These data provide
      evidence that the bisnorbiotin and biotin sulfoxide found in human urine are
      biotin metabolites. Furthermore, we infer that chronic consumption of large
      amounts of biotin does not substantially saturate the human biotin pathways of
      biotransformation.

PMID- 9038856
TI  - Persistent glucose production and greater peripheral sensitivity to insulin in
      the neonate vs. the adult.
AB  - Insulin resistance has been reported to partially explain the clinical appearance
      of neonatal hyperglycemia. To determine the relative resistance to insulin of
      glucose production vs. glucose utilization, the euglycemic hyperinsulinemic clamp
      technique was employed for the first time in the human neonate and was combined
      with stable isotopic determination of glucose production and glucose utilization.
      The basal rates of glucose production and glucose utilization were determined,
      after which each neonate was clamped at his or her own euglycemic glucose
      concentration while receiving regular human insulin at one rate of 0.2, 0.5, 1.0,
      2.0, or 4.0 mU. kg-1.min-1. Persistent glucose production (> or = 1 mg.kg-1.min
      1) during the clamp was recorded for all groups. A significant increase in the
      glucose infusion rate (P < 0.001) and in percent glucose utilization (P < 0.01)
      occurred in the 2.0 and 4.0 mU.kg-1.min-1 insulin groups. Metabolic clearance
      rate of insulin was significantly greater in the neonate compared with the adult
      at the 2.0 mU.kg-1.min-1 insulin infusion rate (P = 0.036). Our results indicate
      that, in contrast to the adult, the neonate has persistent glucose production (P
      = 0.001) and greater peripheral sensitivity to insulin (P = 0.015).

PMID- 9038857
TI  - Effect of rhGH and rhIGF-I treatment on protein utilization in elderly women.
AB  - To assess the effect of recombinant human growth hormone (rhGH) and recombinant
      human insulin-like growth factor I (rhIGF-I) on protein utilization, 14 women,
      age 66-82 yr, were invited to participate in studies of nitrogen balance (n =
      14), whole body protein turnover (n = 14), and muscle protein synthesis (n = 8).
      They were studied both 1 wk before and during the last week of a 1-mo regimen, to
      which they had been randomly assigned, of either 0.025 mg rhGH/kg once daily or
      rhIGF-I at 0.015 (low), 0.03 (mid), or 0.06 (high) mg/kg twice daily. Nitrogen
      balance increased significantly after 1 wk of treatment in all groups (P < 0.05).
      After 1 mo, the magnitude of this effect had diminished by 50% in the rhGH group
      but remained elevated throughout the treatment period with all doses of rhIGF-I.
      Both protein synthesis and breakdown, measured by a primed constant infusion of
      [15N]glycine, were significantly increased with rhGH (9% and 8%, respectively),
      low-dose rhIGF-I (4.5% and 4%), and high-dose rhIGF-I (18% and 17%). Net
      synthesis was significantly increased with rhGH (48%) and high- and mid-dose
      rhIGF-I (27% and 196%, respectively). Muscle protein synthesis as measured by
      incorporation of [1-13C]leucine increased significantly with rhGH (50%) and the
      mid (67%) and high (57%) doses of rhIGF-I. These data show that whole body and
      muscle protein synthesis are responsive to growth factor stimulation in elderly
      women.

PMID- 9038858
TI  - Different physiological traits underlying increased body fat of fatty (fa/fa) and
      heterozygous (+/fa) rats.
AB  - To find out whether the most characteristic physiological traits distinguishing
      suckling-age fa/fa pups from lean littermates also differ between +/+ and +/fa
      littermates, we analyzed the body composition and cold defense of 7- and 16-day
      old pups and the plasma concentrations of insulin, glucose, triglycerides, and
      free fatty acids in 16-day-old pups. Zucker rat x Brown Norway hybrid pups were
      genotyped by using a molecular marker within 0.5 cM of the fa gene. At both ages
      the +/fa pups had significantly more body fat than their +/+ littermates. At 7
      days this difference was as large as that between +/fa and fa/fa pups, but at 16
      days it was only one-seventh of the fa/fa vs. +/fa difference. In contrast, there
      were no heterozygote differences for three parameters that show crucial
      abnormalities in the fa/fa pups: thermoregulatory thermogenesis and plasma
      concentrations of insulin and triglycerides. The physiological mechanisms
      underlying the increased fat content of +/fa pups thus differ from those known to
      fuel most of the excessive fat deposition of their fa/fa littermates.

PMID- 9038860
TI  - Contraction-induced intracellular signals and their relationship to muscle GLUT-4
      concentration.
AB  - This investigation used a model of increased skeletal muscle contractile activity
      to evaluate whether the adenylate cyclase-adenosine 3',5'-cyclic monophosphate
      (cAMP) pathway and/or the high-energy phosphate state of the muscle might be
      temporally related to the contraction-induced increase in skeletal muscle GLUT-4
      protein concentration. Plantaris and gastrocnemius muscles of Sprague-Dawley rats
      were subjected to 3, 7, 14, or 28 days of chronic low-frequency electrical
      stimulation (10 Hz, 24 h/day). GLUT-4 protein concentration was slightly reduced
      after 3 days of electrical stimulation, similar to control values at 7 days and
      significantly elevated above control at 14 days (53%, P < 0.05) and 28 days
      (338%, P < 0.05) of stimulation. ATP, creatine phosphate, creatine, and P, were
      inversely related to GLUT-4 protein concentration. Adenylate cyclase activity
      increased with electrical stimulation and was significantly related to the
      increased GLUT-4 protein. cAMP was significantly increased at 14 days of
      stimulation and remained elevated through 28 days. These results demonstrate that
      both the adenylate cyclase-cAMP pathway and the high-energy phosphate state of
      the muscle are temporally related to elevations in skeletal muscle GLUT-4 protein
      concentration in response to chronic low-frequency electrical stimulation and, as
      such, suggest that both may comprise a component of the intracellular signal that
      regulates the contraction-induced increase in skeletal muscle GLUT-4 protein
      concentration.

PMID- 9038859
TI  - Leucine metabolism in chronically hypoglycemic hypoinsulinemic growth-restricted
      fetal sheep.
AB  - We measured leucine flux rates during infusions of L-[1-14C]- and L-[1-1C]leucine
      in fetal sheep exposed to maternal insulin-induced hypoglycemia over the last 8
      wk (40%) of gestation to determine effects of chronic glucose deficiency and
      hypoglycemia on fetal leucine metabolism. Compared with control fetuses (C, n =
      5), hypoglycemic fetuses (HG, n = 8) weighed less (C, 3.43 +/- 0.07 kg; HG, 2.32
      +/- 0.24 kg), had lower plasma glucose (C, 1.04 +/- 0.02 mM; HG, 0.59 +/- 0.01
      mM), insulin (C, 48 +/- 6 pM; HG, 12 +/- 6 pM), and leucine concentrations (C,
      195.6 +/- 8.3 microM; HG, 140.8 +/- 15.0 microM), lower rates of net leucine
      uptake (C, 4.2 +/- 0.6 mumol.min-1.kg-1; HG, 2.1 +/- 0.4 mumol.min-1.kg-1) and
      leucine flux into protein accretion (C, 2.8 +/- 0.2 mumol.min-1.kg-1; HG, 0.6 +/-
      0.1 mumol.min-1.kg-1), and an increased rate of leucine release from protein
      breakdown (C, 1.1 +/- 0.1 mumol.min-1.kg-1; HG, 3.3 +/- 0.2 mumol.min-1.kg-1) (P
      < 0.05 for all). Plasma leucine disposal, flux into protein synthesis, and
      oxidation were not different between groups. We conclude that adaptations of
      fetal leucine metabolism to long-term hypoglycemia and decreased glucose apply
      represent diminished leucine uptake and increased leucine release from protein
      breakdown, which are associated with decreased incorporation of leucine into
      protein accretion and a slower rate of fetal growth.

PMID- 9038861
TI  - Mechanisms of centrally administered ET-1-induced increases in systemic arterial
      pressure and AVP secretion.
AB  - Endothelins (ET) within the central nervous system (CNS) alter systemic
      cardiovascular responses and arginine vasopressin (AVP) secretion. These
      experiments were designed to ascertain whether the rise in systemic arterial
      pressure after central administration of ET-1 is mediated by enhancing
      sympathetic outflow and/or circulating AVP. In Long-Evans (LE/LE) rats,
      intracerebroventricular injection of 1-10 pmol ET-1 dose dependently increased
      mean arterial pressure (MAP). Peak response occurred 7-12 min after ET-1 and was
      inhibited by ETA receptor antagonism. Systemic vasopressin (V1) receptor blockade
      did not inhibit the pressor response, and rats with central diabetes insipidus
      (DI/DI) displayed an identical rise in MAP. Ganglionic blockade prevented ET-1
      induced hemodynamic effects. Peak plasma AVP levels occurred 60 min after ET-1,
      as the pressor response began to wane. In sinoaortic-denervated LE/LE rats, ET-1
      elicited a 10-fold increase in AVP secretion that coincided with the hemodynamic
      changes and was blocked by BQ-123. Thus ET-1 via ETA receptors within the CNS
      induced a concentration-dependent increase in systemic arterial pressure mediated
      by enhanced sympathetic outflow but not by circulating AVP. Reflex baroreceptor
      activation attenuated AVP release.

PMID- 9038862
TI  - Insulin regulates liver glycogen synthase and glycogen phosphorylase activity
      reciprocally in rhesus monkeys.
AB  - In skeletal muscle of both humans and monkeys, the effects of in vivo insulin
      during a euglycemic hyperinsulinemic clamp on the enzymes and substrates of
      glycogen metabolism have been well established. In liver, such effects of insulin
      during a clamp have not been previously studied in primates. To examine insulin
      action at the liver, euglycemic hyperinsulinemic clamps were performed in 10 lean
      young adult male rhesus monkeys. Liver biopsies were obtained at three time
      points: basal (fasting), that is, immediately before the onset of the clamp, and
      during insulin infusion at 130 and 195 min. Glycogen synthase (GS), glycogen
      phosphorylase (GP), glucose 6-phosphate (G-6-P), and glycogen were determined at
      each time point, with the greatest effects observed most frequently at 195 min.
      Whole body insulin-mediated glucose disposal rate was related to the change in
      the independent activity of GS (r = 0.63, P < 0.05). Insulin increased the GS
      fractional activity (P < 0.005) and decreased the activity ratio of GP (P <
      0.001) compared with basal. The changes in fractional activity of GS and in
      activity ratio of GP were inversely related (r = - 0.68, P < 0.05), G-6-P
      concentration was decreased during insulin stimulation compared with basal (P =
      0.01). Glycogen concentration was not significantly different between the basal
      and insulin-stimulated time points. We conclude that insulin during a euglycemic
      clamp activates liver GS while inhibiting liver GP and that insulin action on
      liver GS is positively related to whole body insulin-mediated glucose disposal
      rates in lean young adult rhesus monkeys.

PMID- 9038864
TI  - Time course of insulin resistance associated with feeding dogs a high-fat diet.
AB  - The current study evaluated both the time course of insulin resistance associated
      with feeding dogs a high-fat diet and the relationship between the development of
      insulin resistance and the increase in blood pressure that also occurs. Twelve
      adult mongrel dogs were chronically instrumented and randomly assigned to either
      a control diet group (n = 4) or a high-fat diet group (n = 8). Insulin resistance
      was assessed by a weekly, single-dose (2 mU.kg-1.min-1) euglycemic
      hyperinsulinemic clamp on all dogs. Feeding dogs a high-fat diet was associated
      with a 3.7 +/- 0.5 kg increase in body weight, a 20 +/- 4 mmHg increase in mean
      blood pressure, a reduction in insulin-mediated glucose uptake [(in mumol-kg
      1.min-1) decreasing from 72 +/- 6 before to 49 +/- 7 at 1 wk, 29 +/- 3 at 3 wk,
      and 30 +/- 2 at 6 wk of the high-fat diet, P < 0.01]. and a reduced insulin
      mediated increase in cardiac output. In eight dogs (4 high fat and 4 control),
      the dose-response relationship of insulin-induced glucose uptake also was
      studied. The whole body glucose uptake dose-response curve was shifted to the
      right, and the rate of maximal whole body glucose uptake was significantly
      decreased (P < 0.001). Finally, we observed a direct relationship between the
      high-fat diet-induced weekly increase in mean arterial pressure and the degree to
      which insulin resistance developed. In summary, the current study documents that
      feeding dogs a high-fat diet causes the rapid development of insulin resistance
      that is the result of both a reduced sensitivity and a reduced responsiveness to
      insulin.

PMID- 9038863
TI  - Aging alters calcium regulation of serum concentration of parathyroid hormone in
      healthy men.
AB  - We examined the effect of aging on the relationship between the concentrations of
      blood ionized calcium and of serum parathyroid hormone (PTH) in 22 healthy men [9
      elderly (age 74 +/- 2 yr) and 13 young (age 39 +/- 1 yr)] in whom the glomerular
      filtration rate was > 70 ml/min. Throughout a 24-h period, serum concentrations
      of PTH in the elderly men were twice those in the young men, whereas blood
      ionized calcium did not differ between the two groups. With intravenous infusion
      of calcium gluconate, the minimum PTH concentration was two- to threefold higher
      in the elderly men. With infusion of NaEDTA. the maximum PTH concentration was
      20% higher in the elderly men. The calcium set point for PTH release was higher
      in the elderly than in the young men (4.71 +/- 0.04 vs. 4.54 +/- 0.03 mg/dl,
      respectively, P < 0.005). In these healthy men, the age-related increase in serum
      PTH could not be attributed to a sustained decrease in concentration of either
      blood ionized calcium or 1,25-hydroxyvitamin D. These findings suggest that, with
      aging, the relationship between calcium and PTH is altered such that at any given
      level of calcium, the concentration of PTH is higher.

PMID- 9038866
TI  - Altered fluxes responsible for reduced hepatic glucose production and
      gluconeogenesis by exogenous glucose in rats.
AB  - The net release of glucose from the liver, or hepatic glucose production (HGP),
      and apparent gluconeogenesis (GNG) are reduced by exogenous glucose. We
      investigated the changes in metabolic fluxes responsible. Flux through the
      hepatic GNG pathway was quantified by mass isotopomer distribution analysis
      (MIDA) from [2-13C]glycerol. Unidirectional flux across hepatic glucose-6
      phosphatase (G-6-Pase), or total hepatic glucose output (THGO), and hepatic
      glucose cycling (HGC) were also measured by using glucuronate (GlcUA) to correct
      for glucose 6-phosphate (G-6-P) labeling. Infusion of glucose (15-30 mg.kg-1.min
      1 iv) to 24 h-fasted rats caused two important metabolic alterations. First was a
      significant increase in hepatic glucose uptake and HGC: > 60% of THGO was from
      HGC. Second, although flux through hepatic G-6-P increased (from 15.7 to 17.7
      22.7 mg.kg-1.min-1), the partitioning of G-6-P flux changed markedly [from 30-35%
      to 55-60% entering UDP-glucose (UDP-Glc), P < 0.01]. Total flux through the GNG
      pathway remained active during intravenous glucose, but increased partitioning
      into UDP-Glc lowered GNG flux plasma glucose by 50%. In summary, the suppression
      of HGP and GNG flux into glucose is not primarily due to reduced carbon flow
      through hepatic G-6-Pase or the hepatic GNG pathway. THGO persists, but hepatic G
      6-P is derived increasingly from plasma glucose, and flow through GNG persists,
      but the partitioning coefficient of G-6-P into UDP-Glc doubles. These adjustments
      permit net HGP to fall despite increased total production of hepatic G-6-P during
      administration of glucose.

PMID- 9038865
TI  - Measurement of hepatic Ra UDP-glucose in vivo in rats: relation to glycogen
      deposition and labeling patterns.
AB  - We previously described an isotopic method for quantifying the rate of appearance
      of hepatic UDP-glucose (Ra UDP-Glc) and the direct entry of glucose into hepatic
      UDP-Glc in humans. Here, the method is tested in depth in rats. The basic
      principles are that dilution of labeled galactose in hepatic UDP-Glc, sampled
      noninvasively by the xenobiotic glucuronate (GlcUA) method, reveals Ra UDP-Glc.
      First, labeling patterns in secreted acetaminophen-GlcUA were compared with
      hepatic glycogen and plasma glucose by use of mass isotopomer distribution
      analysis from [2-(13)C]glycerol. Labeling was consistent with common precursor
      pools of glucose 6-phosphate and triose-phosphate for all end products studied in
      fasted and in intravenous glucose- and fructose-infused states. Next, [1
      (3)H]galactose was administered. After a 24-h fast, Ra UDP-Glc was 25.0 +/- 1.7
      mumol.kg body wt-1.min-1 and rose to 57.7 and 72.7 mumol.kg-1.min-1 at
      intravenous glucose infusion rates of 111 and 167-194 mumol.kg-1.min-1,
      respectively. Liver glycogen deposition correlated closely with Ra UDP-Glc (R2 =
      0.76), although the turnover value was approximately 50% higher than the net
      deposition rate. In conclusion, the turnover of an intrahepatic metabolite, UDP
      Glc, can be measured noninvasively, and Ra UDP-Glc correlates with liver glycogen
      deposition in rats.

PMID- 9038867
TI  - Altered metabolism and superoxide generation in neural tissue of rat embryos
      exposed to high glucose.
AB  - Oxygen uptake and glucose utilization of embryonic and fetal neural tissue of
      normal and diabetic rat pregnancy were studied. Exposure to 50 mM glucose
      inhibited oxygen uptake of embryonic neural tissue of normal rats by 28% at
      gestational day 9 (P < 0.001) and 20% at days 10-12 and 15 (P < 0.001) and
      stimulated glucose utilization by 132% at day 9 (P < 0.001), 50% at days 10 and
      11 (P < 0.01), 168% at day 12 (P < 0.001), and 338% at day 15 (P < 0.001),
      indicating a Crabtree effect. The glucose-altered metabolism led to production of
      superoxide by the tissue, which was 1.8 to 2.4 nmol.h-1.microgram DNA-1 at days 9
      12 and 1.2 nmol.h-1.microgram DNA-1 at day 15. The embryonic neural tissue of
      diabetic rats showed a diminished metabolic sensitivity to high glucose exposure,
      suggesting an impaired mitochondrial function. Consequently, the glucose-induced
      superoxide production was not detected in the tissue of embryos of diabetic rats.
      The data suggest that high concentration of glucose alters embryonic and fetal
      metabolism and causes generation of superoxide. Prolonged duration of the glucose
      induced metabolic changes may impair cellular function and lead to embryonic
      dysmorphogenesis.

PMID- 9038868
TI  - Evidence for diminished visceral pain with aging: studies using graded
      intraesophageal balloon distension.
AB  - Graded intraesophageal balloon distension (IEBD) has been utilized in the past to
      evaluate esophageal pain thresholds. With use of a technique that we have found
      to provide reproducible results for pain thresholds, two groups of normal
      individuals without esophageal symptoms or diabetes were studied. Group 1
      included 10 "young" (age < 65 yr) individuals (mean age 27 yr, range 18-57 yr).
      Group 2 included 17 individuals age 65 yr or greater (mean age 72.5 yr, range 65
      87 yr). Catheters with latex balloons (Wilson-Cook) were used in all 27 subjects
      with the balloon located 10 cm above the lower esophageal sphincter. Sequential
      inflations of 2-ml increments were performed until a total volume of 2 ml above
      the point of pain or to a maximum of 30 ml was reached. A series of two
      sequential inflations were performed on each subject on the day of the testing,
      and the mean value was taken to indicate pain threshold volumes for all 27
      subjects. In the group of elderly volunteers, 5 subjects felt no pain even at the
      maximum inflatable volume of the balloon (30 ml) and were assigned a maximum
      threshold value of 30 ml. Mean pain threshold volumes for the young subjects was
      17 +/- 0.8 ml of air (+/- SE) and for the elderly subjects was 27 +/- 1.4 ml (P <
      0.01 and 95% confidence interval = 7.1-13.3). Our conclusion is that IEBD results
      in the esophagus indicate an age-related decrease in human visceral pain
      threshold.

PMID- 9038869
TI  - Regulation of motilin release: studies with ex vivo perfused canine jejunum.
AB  - The regulatory process of motilin release was studied in segments of canine
      jejunum isolated and perfused ex vivo. The secretion of motilin in the effluent
      venous system of the isolated intestine was measured by radioimmunoassay in
      response to various pharmacological agents injected intra-arterially. Muscarinie
      agonist and antagonist, respectively, increased and decreased the release of
      motilin. The stimulatory effect of carbachol was still documented after
      tetrodotoxin (10(-5) M) was injected in the system to block neural influence on M
      cells. Bombesin and morphine also increased the release of motilin. The effect of
      bombesin was still documented in the presence of atropine or tetrodotoxin, but
      the stimulatory morphine effect was blocked by atropine. Both phenylephrine and
      octreotide decreased the release of motilin stimulated by carbachol in a jejunal
      segment pretreated and denervated with tetrodotoxin. Therefore, a revised model
      for the regulation of motilin release from M cells of intestinal mucosa can now
      be proposed. Cholinergic and bombesin receptors are present on M cells to encode
      a stimulatory signal, whereas adrenergic and somatostatin receptors are
      responsible for inhibitory transmission. The stimulatory effect of morphine is
      mediated via a muscarinic transmitter.

PMID- 9038870
TI  - Incrimination of anaerobic bacteria in the induction of experimental colitis.
AB  - Commensal bacteria may participate in the pathogenesis of bowel inflammation. We
      studied the role of bacteria from the rat colonic flora on transmural
      inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). First,
      bacterial translocation to the colonic wall after induction of colitis was
      assessed by microbiological and histological methods. Second, rats with a colonic
      segment excluded from fecal transit were prepared for recolonization with
      preselected bacteria and used to test the effects of different species on
      inflammation (eicosanoid release, tissue myeloperoxidase) and damage (histology).
      Six strains (three aerobes and three anaerobes) were identified in colonic tissue
      24 h after induction of colitis. Acridine staining showed bacteria in necrotic
      areas of the mucosa and invading the submucosa. Rats with excluded colon and
      sterile culture of luminal washings showed mild inflammation and low mucosal
      damage in response to TNBS. Rats colonized with anaerobes showed significantly
      higher eicosanoid release than rats colonized with aerobes only. Moreover,
      submucosal-lesions were mostly observed in rats with anaerobes. Our findings
      suggest that colonic anaerobes play a key role in transmural inflammation.

PMID- 9038871
TI  - Molecular cloning of canalicular multispecific organic anion transporter
      defective in EHBR.
AB  - Several organic anions are excreted into the bile via a canalicular multispecific
      organic anion transporter (cMOAT), which is hereditarily defective in mutant
      rats, such as the Eisai hyperbilirubinemic rat (EHBR) and TR- rat. In the present
      study, we cloned cMOAT from the Sprague-Dawley rat liver cDNA library based on
      the homology with human multidrug resistance-associated protein (hMRP). cMOAT was
      encoded by 4,623-base pair (bp) cDNA with a homology of 53.0 and 46.3% with hMRP
      at the cDNA and deduced amino acid level, respectively. The deduced amino acid
      sequence was the same as that cloned in Wistar rats (C. C. Paulusma, P. J. Bosma,
      G. J. Zaman, C. T. Bakker, M. Otter, G. L. Sceffer, P. Borst, and R. P. Oude
      Elferink. Science Wash. DC 271: 1126, 1996) except for four amino acid
      substitutions. By screening the library, three kinds of cDNA species for cMOAT
      with the same open reading frame and different 3'-untranslated region lengths
      (0.2, 1.5, and 3.5 kbp) were isolated. The Northern blot analysis of poly(A)+ RNA
      from the liver revealed that the expression of plural bands (approximately 5, 6,
      and 8 kb) was defective in EHBR, and this may be due to the presence of these
      cDNA species. Expression of cMOAT was observed almost exclusively in the liver
      and to a lesser extent in the duodenum, kidney, and jejunum. Reverse
      transcription-polymerase chain reaction (RT-PCR) and subsequent sequence analysis
      of EHBR liver, kidney, duodenum, and jejunum revealed that 1-bp replacement from
      G to A at nucleotide 2564 resulted in the introduction of the premature stop
      codon in all tissues examined. This mutation was different from that observed in
      TR (C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L.
      Sceffer, P. Borst, and R. P. Oude Elferink. Science Wash. DC 271: 1126, 1996).
      Because EHBR and TR- are allelic mutants and both strains exhibit an autosomal
      recessive inheritance in the biliary excretion of organic anions it was concluded
      that the impaired expression of this particular protein is related to the
      pathogenesis of hyperbilirubinemia in the mutant animals.

PMID- 9038872
TI  - Protective effects of prostaglandin E1 on acute lung injury of caerulein-induced
      acute pancreatitis in rats.
AB  - Infusion of a supramaximally stimulating dose of the pancreatic secretagogue
      caerulein (10 micrograms.kg-1.h-1) for 4 h induces interstitial edematous acute
      pancreatitis in rats. This model of acute pancreatitis is associated with
      evidence of acute lung injury, including sequestered neutrophils within the
      pulmonary microvasculature, increased microvascular permeability, and
      interstitial pulmonary edema. Infusion of prostaglandin E1 (PGE1; 50 ng.kg-1.min
      1) along with caerulein does not alter the severity of secretagogue-induced
      pancreatitis, but it does reduce the severity of pancreatitis-associated acute
      lung injury. The rise in lung weight, lung water content, and pulmonary
      microvascular permeability and the sequestration of neutrophils within the
      pulmonary microvasculature that accompany secretagogue-induced pancreatitis are
      all reduced by infusion of PGE1. Infusion of PGE1 does not interfere with
      polymorphonuclear neutrophil sequestration in the pancreas or reduce the enhanced
      expression of CD11b/c receptors on circulating neutrophils. Our observations
      indicate that PGE1 reduces the severity of pancreatitis-associated acute lung
      injury by preventing neutrophil sequestration within the lung. We speculate that
      PGE1 interferes with neutrophil sequestration by dilating pulmonary vasculature,
      increasing pulmonary flow rate, and reducing neutrophil-endothelial cell
      interaction and attachment.

PMID- 9038873
TI  - Protein kinase C-epsilon is the likely mediator of mucin exocytosis in human
      colonic cell lines.
AB  - The phorbol ester, phorbol 12-myristate 13-acetate (PMA), induces mucin secretion
      in the colonic tumor cell line T84 in a Ca(2+)-independent manner. To determine
      whether a specific protein kinase C (PKC) isoform is involved in colonic cells,
      we compared PMA-dependent mucin secretion by three human colonic tumor cell lines
      (T84, HT-29/A1, and LS 180) with the expression of PKC isoforms alpha, beta,
      delta, epsilon, and zeta, previously identified in human colon (L. A. Davidson,
      Y. H. Jiang, J. D. Derr, H. Aukema, J. R. Lupton, and R. S. Chapkin. Arch.
      Biochem. Biophys. 312:547-553, 1994). In each cell line PMA (10(-7) M) caused
      mucin secretion within 30 min. PMA-dependent mucin secretion was three to four
      times greater from HT-29/A1 and T84 cells than from LS 180 cells. All three-cell
      lines contained mRNA for PKC-alpha, PKC-epsilon, and PKC-zeta but not PKC-beta or
      -delta. Each cell line also expressed PKC-alpha, -epsilon, and -zeta protein. PKC
      epsilon expression (mRNA and protein) was three to four times greater in HT-29/A1
      and T84 cells than in LS 180 cells, correlating with PMA-responsive mucin
      secretion, whereas all cell lines contained similar levels of PKC-alpha mRNA and
      protein. When cells were stimulated by PMA, only PKC-epsilon was translocated
      from cytosol to membrane fractions early enough to stimulate mucin secretion.
      Because PKC-epsilon is also a Ca(2+)-independent isoform, it is likely to mediate
      mucin exocytosis in colonic cells.

PMID- 9038874
TI  - Endogenous adenosine inhibits evoked substance P release from perifused networks
      of myenteric ganglia.
AB  - Isolated myenteric ganglion networks were prepared from guinea pig ileum and were
      used in a perifusion protocol to examine the effects of interstitial adenosine on
      evoked release of substance P-like immunoreactivity (SPLI). The release of SPLI
      evoked by elevated extracellular K+ concentration was increased in the presence
      of tetrodotoxin (TTX), indicating tonic inhibition of SPLI release and revealing
      net inhibitory interganglionic transmission. Perifusion in the presence of the
      adenosine A1 receptor-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine
      enhanced evoked SPLI release, which was further enhanced in the additional
      presence of TTX, indicating that adenosine contributes some, but not all, of the
      overall inhibitory tone within the networks. In addition to neural release of
      adenosine per se, an additional source was investigated. Perifusion in the
      presence of alpha, beta-methylene-ADP plus guanosine 5'-monophosphate, which
      inhibits ecto-adenosinetriphosphatase (ATPase) activity, enhanced SPLI release,
      indicating that hydrolysis of released ATP contributes to the total interstitial
      nucleoside concentration and thereby to the overall inhibitory tone. It is
      concluded that endogenous adenosine, some of which arises from ATP metabolism, is
      an important contributor to the overall inhibitory tone present in myenteric
      ganglion networks.

PMID- 9038875
TI  - Prolactin increases ATP-dependent taurocholate transport in canalicular plasma
      membrane from rat liver.
AB  - The taurocholate (TC) maximal secretory rate (SRm) in the isolated perfused liver
      is increased in postpartum rats and ovariectomized rats treated with ovine
      prolactin (oPRL). The present studies were designed to characterize the
      mechanism(s) by which oPRL increases TC transport in the liver. oPRL (300
      micrograms/day i.v. for 7 days) increased the SRm 1.6-fold from 185 to 364
      nmol.min-1.mg protein-1 in the perfused rat liver and the maximal rate of
      transport for ATP-dependent transport 1.7-fold from 66 to 109 nmol.min-1.mg
      protein-1 in canalicular liver plasma membrane (cLPM) vesicles without changing
      the Michaelis constant (5-6 microM). The oPRL-mediated increases in biliary
      excretion in the perfused liver and ATP-dependent TC transport in cLPM vesicles
      were significantly inhibited by cycloheximide treatment (2 mg/kg). oPRL (300
      micrograms/day iv for 7 days) increased expression of Ca(2+)-Mg(2+)-ecto
      adenosinetriphosphatase mRNA sixfold and increased protein expression two- to
      threefold, but had no effect on the expression of P-glycoprotein (mdr1b and mdr2)
      mRNA. Thus the increase in ATP-dependent transport in cLPM vesicles due to oPRL
      treatment accounts for the increased TC SRm in the perfused liver. The oPRL
      mediated increased TC transport may be associated with increased expression of
      proteins related to bile acid transport.

PMID- 9038876
TI  - Net H+ and K+ fluxes across the apical surface of rat distal colon.
AB  - The distal colon absorbs K+ (JK) and secretes H+ (JH) by what is thought to be an
      H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase). However, the colonic ATPase
      differs structurally and functionally from the gastric H(+)-K(+)-ATPase. To
      evaluate the link between JH and JK, JH and JK were simultaneously measured with
      ion-specific electrodes in segments of rat distal colon. JH and JK averaged 0.40
      +/- 0.03 and 0.30 +/- 0.03 mu eq.h-1.cm-2 (n = 191), but JH and JK did not
      correlate (r = 0.005, not significant). The gastric H(+)-K+ pump inhibitors SCH
      28080 (100 microM) and omeprazole (100 microM), as well as a vacuolar H(+)-ATPase
      inhibitor, bafilomycin A1 (10 microM), did not affect JH or JK. However, the
      Na(+)-K(+)-ATPase inhibitors ouabain (1 mM) and N-ethylmaleimide (10 microM)
      inhibited JK but not JH. Although 1 mM orthovanadate inhibited both JH and JK, at
      lower concentrations orthovanadate only affected JK. Furthermore, removing K+
      from the medium did not affect JH. Secondary hyperaldosteronism increased both JH
      and JK; however, ouabain (1 mM) reduced JK but not JH. Cl(-)-free medium
      inhibited voltage-insensitive JH and voltage-sensitive JK. Medium pH affected JH,
      but that effect was contrary to the effect that pH had on Rb+ flux. These data
      failed to identify a relationship between JH and JK and appear to suggest that JH
      and JK occur by separate pathways.

PMID- 9038877
TI  - Gastric mucus of the guinea pig: proton carrier and diffusion barrier.
AB  - Proton transport with the gastric mucus was investigated in the guinea pig in
      vitro by use of three experimental series. In series I, pH profiles were obtained
      in the mucus and mucosa of a gastric explant with fine-tipped double-barreled
      microelectrodes. With a luminal pH of 1.8, pH increased across this layer to
      approximately 6 at the epithelial surface. Thickness of the gastric mucous gel
      layer increased continuously by 170 +/- 100 microns/h in the unstimulated and by
      450 +/- 120 microns/h in the histamine-stimulated preparation (means +/- SD). In
      series II, fresh guinea pig gastric mucus was obtained from the gastric mucosa
      and titrated at 10 degrees C from pH 6.5 to 0.7, followed by an incubation period
      of 30 min at 37 degrees C. During this incubation period, a spontaneous acidic
      shift was observed, corresponding to a proton release from the mucus of 130 +/-
      19 mM. This proton release could be blocked by the pepsin inhibitor pepstatin and
      was not observed when titrating down to only pH 3. Buffer values calculated as
      the mean slope of the titration curves in the pH range of 7 to 3 averaged 40
      mM/pH unit. In series III, when titration was repeated with purified porcine
      mucin, no proton release was observed during incubation at pH 1.0, unless
      pepsinogen (375 U/ml) had been added before titration. Proton release during
      incubation at pH 1.0 and 37 degrees C in the presence of pepsinogen averaged 50
      mM. The data suggest that protons secreted by the gastric mucosa are buffered by
      the continuously secreted mucus and transported, bound to the proteins of the
      mucus, toward the gastric lumen. During this transport, pepsinogen is converted
      within the mucus to pepsin. Pepsin modifies the buffering properties of the
      mucus, whereby protons are released from the protein binding. Thus the mucus
      forms a vehicle for proton transport toward the gastric lumen while, at the same
      time, constituting a diffusion barrier to prevent proton backdiffusion toward the
      gastric epithelium.

PMID- 9038878
TI  - Neural mediation of the motilin motor effect on the human antrum.
AB  - To elucidate the mode of action of motilin on the stimulation of human
      gastrointestinal motility, we studied the effect of exogenous motilin during
      muscarinic or serotoninergic pharmacological blockade. Manometric recording of
      the interdigestive antroduodenal motility was carried out in 27 healthy
      volunteers until the appearance of a spontaneous antral phase III. The tested
      blocker was then administered intravenously and was followed 30 min later by a 10
      min infusion of synthetic human motilin (50 ng/kg). Motilin administered on a
      background of saline induced a premature phase III migrating from the antrum to
      the duodenum in every tested subject (n = 5). A low dose of atropine (5
      micrograms.kg-1.h-1 for 90 min) inhibited the motilin effect in two of five
      subjects [not significant (NS)], whereas a high dose of atropine (15
      micrograms/kg given in 30 min) blocked the motilin-induced premature antral phase
      III in all instances (n = 5, P < 0.01). Exogenous motilin given with low-dose
      ondanseton (8 mg given in 15 min followed by 1 mg/h for 90 min) or high-dose
      ondansetron (32 mg given in 30 min) was without effect in three of seven (NS) or
      in two of five (NS) subjects, respectively. During the administration of 15
      micrograms/kg atropine, when exogenous motilin always failed to induce a
      premature antral phase III motor, a phase III-type activity was generated at the
      duodenum in four of five subjects. We conclude that the induction by motilin of
      phase III activity in human antrum is dependent on muscarinic mediation and that
      the contractile effect of motilin on human duodenum involves a noncholinergic
      mechanism, different therefore from the antral pathway.

PMID- 9038879
TI  - Electrical responses of gastric smooth muscles in streptozotocin-induced diabetic
      rats.
AB  - Electrical responses of gastric smooth muscles produced by transmural nerve
      stimulation, acetylcholine, norepinephrine, or K-free solution were investigated
      in streptozotocin-induced diabetic rats, using intracellular microelectrode
      techniques. In muscles from diabetic rats, 1) the resting membrane potential
      remained unchanged, 2) slow waves disappeared or were markedly reduced in
      amplitude, 3) the excitatory junction potential was absent, and in most cases
      only an inhibitory junction potential of reduced amplitude was elicited, 4) the
      amplitude of the hyperpolarization generated after superfusion with K-free
      solution was reduced, 5) the sensitivity of the acetylcholine-induced membrane
      depolarization was increased, and 6) the norepinephrine-induced hyperpolarization
      was reduced because of functional loss of alpha- and beta-adrenoceptors. Thus
      diabetes mellitus caused functional impairment of neuromuscular transmission,
      reduced the maximum activity of the electrogenic pump, increased the sensitivity
      of muscarinic receptors, reduced the sensitivity of adrenoceptors, and reduced
      the myogenic activity in gastric smooth muscles. These alterations in the
      properties of smooth muscle may be involved in the diabetes-induced
      gastroparesis.

PMID- 9038880
TI  - Stress-induced enhancement of colitis in rats: CRF and arginine vasopressin are
      not involved.
AB  - Because exacerbation of colitis seems to be associated with stress, we proposed
      evaluating the influence of stress and the involvement of corticotropin-releasing
      factor (CRF) and arginine vasopressin (AVP) on experimental colitis in rats.
      Partial restraint stress was applied during 4 consecutive days, before or after
      intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNB) instillation (15 mg) in
      rats. Finally, two groups of rats were centrally injected with alpha-helical CRF
      (9-41) (5 micrograms) or AVP antagonist (5 micrograms) before each session of
      stress. Stress was applied before or right after TNB enhanced colitis, with an
      increase in macroscopic and histological scores and myeloperoxidase activity,
      alpha-Helical CRF-(9-41) or AVP antagonist had no effect on TNB-induced colitis
      but enhanced the effects of stress on colitis. These results show that stress may
      exacerbate experimental colitis in rats and that CRF and AVP are not responsible
      for this effect.

PMID- 9038881
TI  - Vasoactive intestinal peptide modulates T lymphocyte migration in Peyer's patches
      of rat small intestine.
AB  - Although vasoactive intestinal peptide (VIP) has been postulated to function in
      modulation of T cell trafficking, the exact mechanism has not been elucidated in
      vivo. In the present study, the effects of VIP on T lymphocyte migration were
      examined in rat Peyer's patches. T lymphocytes collected from intestinal lymph of
      rats were labeled with carboxyfluorescein diacetate succinimidyl ester and
      injected into the jugular vein. Peyer's patches of the recipient rats were
      observed with intravital fluorescence microscopy. In vivo intra-arterial infusion
      of or in vitro incubation with VIP did not affect the initial lymphocyte
      interaction with postcapillary venules of Peyer's patches. However, these
      treatments with VIP significantly inhibited transendothelial migration and also
      significantly blocked the interstitial migration of T cells and inhibited their
      subsequent appearance in the interfollicular lymphatics. Treatment with adenosine
      3',5'-cyclic monophosphate (cAMP)-inducing agents resulted in similar inhibitory
      effect on T lymphocyte migration in Peyer's patches. In conclusion, VIP has
      significant inhibitory effects on T lymphocyte migration in Peyer's patches,
      possibly mediated by elevation of the intracellular cAMP concentrations.

PMID- 9038882
TI  - Endogenous CCK disrupts the MMC pattern via capsaicin-sensitive vagal afferent
      fibers in the rat.
AB  - A meal disrupts migrating motor complexes (MMC) in the rat intestine through
      stimulation of peripheral cholecystokinin (CCK)-B and central CCK-A receptors.
      The aim of this study was to determine pathways implicated in postprandial
      disruption of the MMC mediated by CCK. Sprague-Dawley rats were prepared with
      electrodes for electromyography in the small intestine, and ablation of vagal
      afferent C-fibers by capsaicin was carried out. Endogenous release of CCK was
      induced by oral administration of soybean trypsin inhibitor (SBTI). In control
      rats SBTI disrupted MMC and generated an irregular spiking activity that lasted
      longer than 3 h. Intravenous infusion of L-365,260 (2 x 10(-7) mol/kg) but not of
      L-364,718 (3 x 10(-9) mol/kg) restored the MMC pattern. In capsaicin-treated
      rats, SBTI did not modify fasting activity. Infusion of CCK octapeptide (CCK-8)
      at 3 x 10(-9) mol.kg-1.h-1 disrupted the MMC, although the response was
      quantitatively and qualitatively different from SBTI. The effect was reversed by
      intravenous infusion of L-364,718 or L-365,260 and intracerebroventricular
      infusion of L-364,718. In capsaicin-treated rats, the intracerebroventricular or
      intravenous infusion of L-364,718 inhibited CCK-8 effects. However, the
      intravenous infusion of L-365,260 did not reverse the MMC pattern. These results
      suggest that the disruption of the MMC mediated by CCK is due to stimulation of
      peripheral CCK-B receptors located in vagal afferent fibers. This initiates a
      reflex including stimulation of central CCK-A receptors. Exogenous CCK also
      stimulates peripheral CCK-A receptors not located in capsaicin-sensitive vagal
      afferent fibers.

PMID- 9038883
TI  - Development and initial application of an in vitro model of apoptosis in rodent
      cholangiocytes.
AB  - Although histological data suggest that cholangiocytes die by apoptosis in human
      liver diseases, no information exists on the mechanisms of cholangiocyte
      apoptosis. Thus our aims were to establish an in vitro model of cholangiocyte
      apoptosis and to test the hypothesis that changes in intracellular ions would
      cause apoptosis in cholangiocytes by a protease-sensitive pathway. A large number
      of proapoptotic agents were ineffective in inducing apoptosis in rat or human
      cholangiocytes in culture; in contrast, beauvericin, a K+ ionophore, caused
      apoptosis in both cell lines, despite their expression of Bcl-2. Although
      beauvericin decreased intracellular K+ and increased intracellular Ca2+,
      abolishing the K+ gradient did not prevent beauvericin-induced apoptosis; in
      contrast, omission of extracellular Ca2+ inhibited apoptosis by 42%. The
      interleukin-1 beta-converting enzyme (ICE) family protease inhibitor, Z-Val-Ala
      Asp chloromethylketone, inhibited apoptosis in a concentration-dependent manner.
      By Northern blot analysis, cholangiocytes expressed the mRNA for three members of
      the ICE protease family: ICE, ICE/ CED-3 homologue-1 (ICH-1), and cysteine
      protease P-32 (CPP-32). Cleavage of a substrate for CPP-32-like protease
      activity, but not a substrate for ICE and ICH-1, increased after beauvericin
      treatment. In summary, we have established an in vitro model of apoptosis in
      cholangiocytes. Our data suggest that beauvericin-induced apoptosis occurs by a
      Ca(2+)-dependent CPP-32 protease-sensitive pathway despite cholangiocyte
      expression of Bcl-2.

PMID- 9038884
TI  - Effect of vitamin E supplementation on hepatic fibrogenesis in chronic dietary
      iron overload.
AB  - It has been suggested that lipid peroxidation plays an important role in hepatic
      fibrogenesis resulting from chronic iron overload. Vitamin E is an important
      lipid-soluble antioxidant that has been shown to be decreased in patients with
      hereditary hemochromatosis and in experimental iron overload. The aim of this
      study was to determine the effects of vitamin E supplementation on hepatic lipid
      peroxidation and fibrogenesis in an animal model of chronic iron overload. Rats
      were fed the following diets for 4, 8, or 14 mo: standard laboratory diet
      (control), diet with supplemental vitamin E (200 IU/kg, control + E), diet with
      carbonyl iron (Fe), and diet with carbonyl iron supplemented with vitamin E (200
      IU/kg. Fe + E). Iron loading resulted in significant decreases in hepatic and
      plasma vitamin E levels at all time points, which were overcome by vitamin E
      supplementation. Thiobarbituric acid-reactive substances (an index of lipid
      peroxidation) were increased three- to fivefold in the iron-loaded livers;
      supplementation with vitamin E reduced these levels by at least 50% at all time
      points. Hepatic hydroxyproline levels were increased twofold by iron loading.
      Vitamin E did not affect hydroxyproline content at 4 or 8 mo but caused an 18%
      reduction at 14 mo in iron-loaded livers. At 8 and 14 mo, vitamin E decreased the
      number of alpha-smooth muscle actin-positive stellate cells in iron-loaded
      livers. These results demonstrate a dissociation between lipid peroxidation and
      collagen production and suggest that the profibrogenic action of iron in this
      model is mediated through effects which cannot be completely suppressed by
      vitamin E.

PMID- 9038885
TI  - Confocal microscopic analysis of intracellular pH regulation in isolated guinea
      pig pancreatic ducts.
AB  - pH regulation in isolated guinea pig pancreatic interlobular duct segments loaded
      with the pH-sensitive fluorophore, 5-(6)-carboxy-SNARF-1-acetoxymethyl ester
      (SNARF-1), was characterized by laser-scanning confocal microscopy. In HCO3(-)
      free medium, intracellular pH (pHi) of duct epithelial cells fell by 0.32 +/-
      0.06 pH units in the presence of 0.5 mM amiloride and by 0.36 +/- 0.08 pH units
      in the absence of Na+. In the presence of extracellular HCO3-, pHi acidified in
      Na(-)-free medium but not in amiloride-containing medium. Superfusion with Cl(-)
      free buffers or with buffers containing 4,4'-diisothiocyanostilbene-2,2'
      disulfonic acid produced a cytosolic alkalinization of 0.13-0.22 pH units. These
      observations demonstrate the presence of Na+/H+ exchange, Na(+)-HCO3-
      cotransport, and Cl-/HCO3- exchange in guinea pig pancreatic ducts. pHi recovered
      significantly from an NH4Cl pulse in HCO3(-)-free buffers containing amiloride
      and carbachol (50.4%) or amiloride and secretin (40.6%). This recovery was
      blocked by the H(+)-adenosinetriphosphatase (H(+)-ATPase) inhibitor bafilomycin
      A1 and by preincubation of ducts with nocodazole or cytochalasin D. These
      observations suggest that a vesicular H(+)-ATPase augments Na(+)-dependent H+
      extrusion during agonist-stimulated bicarbonate secretion and that activation of
      this transport mechanism involves cytoskeletal elements.

PMID- 9038886
TI  - CCK, carbachol, and bombesin activate distinct PLC-beta isoenzymes via Gq/11 in
      rat pancreatic acinar membranes.
AB  - Four different isoforms of phospholipase C-beta (PLC-beta 1-4) have been
      discovered, raising the important question of whether a distinct receptor
      activates a single PLC-beta isoenzyme or a subset of PLC-beta isoenzymes. The
      present study was designed to investigate activation of PLC-beta isoenzymes by
      three different PLC-activating agonists that bind to different receptor entities,
      i.e., cholecystokinin octapeptide (CCK-8), bombesin, and carbachol in rat
      pancreatic acinar membranes. PLC activity was measured using exogenous
      [3H]phosphatidylinositol 4,5-bisphosphate as substrate. Western blot analysis of
      pancreatic acinar membranes revealed the presence of PLC-beta 1, -beta 3, -gamma
      1, and -delta 1, but not of PLC-beta 2, -beta 4, -gamma 2, and -delta 2.
      Preincubation of the membranes with anti-PLC-beta 1 or -beta 3 antibody reduced
      agonist-induced activation of PLC. The order of sensitivity toward inhibition by
      anti-PLC-beta 1 antibody was CCK-8 > bombesin > carbachol. An opposite order of
      sensitivity was found for inhibition of PLC activity by anti-PLC-beta 3 antibody
      (carbachol > bombesin > CCK-8). Anti-PLC-beta 2, -beta 4, -gamma 1, -gamma 2, 
      delta 1, and -delta 2 antibodies had no effect. Preincubation of the membranes
      with an antibody raised against the COOH terminus of the alpha-subunit of Gq/11
      proteins inhibited PLC activity in response to all three different receptor
      agonists to a similar extent, whereas anti-Gi alpha 1-2 and anti-Gi alpha 3
      antibodies had no effect. In conclusion, the data of the present study indicate
      that CCK-8 and carbachol activate PLC-beta 1 and PLC-beta 3, respectively,
      whereas bombesin activates both PLC-beta 1 and PLC-beta 3. Activation of PLC-beta
      by these receptor agonists is mediated by Gq/11.

PMID- 9038887
TI  - Tachykininergic mediation of viscerosensitive responses to acute inflammation in
      rats: role of CGRP.
AB  - Tachykinins, colocalized with calcitonin gene-related peptides (CGRP) in sensory
      afferents, are involved in viscerosensitive responses. We investigated the role
      of tachykinins and CGRP in both nociceptive and visceromotor responses to
      inflammation. Visceral pain was assessed by abdominal muscle contractions.
      Gastric emptying was evaluated after gavage with reconstituted milk containing
      51Cr-labeled sodium chromate. Acetic acid or 9% NaCl was injected
      intraperitoneally before the meal. RP-67580, SR-48968, human CGRP [hCGRP-(8-37)],
      or their vehicles were injected before acetic acid or saline. RP-67580, SR-48968,
      or their vehicles were injected before CGRP and the meal. GR-73632 or GR-76349
      was injected before the meal. Acetic acids inhibited gastric emptying and
      increased the number of abdominal contractions. RP-67580 reduced the inhibition
      of gastric emptying without affecting the abdominal response. SR-48968 only
      reduced the acetic acid-induced increase of abdominal contractions. hCGRP-(8-37)
      reduced both responses induced by acetic acid. CGRP mimicked the effects of
      acetic acid. RP-67580 abolished CGRP-induced gastric emptying inhibition, whereas
      SR-48968 only diminished visceral pain. GR-73632 reduced gastric emptying, and GR
      64349 increased abdominal response. In inflammation, neurokinin receptors (NK1
      and NK2) mediate the gastric emptying inhibition and visceral pain, respectively.
      These responses involve a release of CGRP.

PMID- 9038888
TI  - Local regulation of ileal tone in healthy humans.
AB  - We previously showed that a meal induced, in the human terminal ileum, a delayed
      tonic relaxation, which could be related to the ileal delivery of meal residues
      and/or endogenous secretions released by a meal. In this study, we assessed the
      effects of some components of the ileal contents on its motor activity. In six
      healthy subjects, we studied ileal tonic and phasic motility in response to the
      infusion into the terminal ileum of different isotonic solutions: saline,
      glycochenodeoxycholic acid (GDCA), triglycerides, and short-chain fatty acids
      (SCFA). Tonic activity was not modified by saline, whereas it was significantly
      decreased by GDCA and triglycerides (maximal increase in intrabag volume 139 +/-
      7% and 152 +/- 16%, respectively, P < 0.01), and significantly increased by SCFA
      (maximal decrease in intrabag volume 72 +/- 4%, P < 0.01). No significant change
      of phasic activity was evidenced with either solution. We conclude that 1) bile
      acids and triglycerides not absorbed in the more proximal gut could be involved
      in the ileal relaxation occurring after eating and 2) local stimulation of
      chemoreceptors is of importance in the regulation of ileal motility.

PMID- 9038889
TI  - Importance of vagus nerves in duodenal acid neutralization in anesthetized pigs.
AB  - During the cephalic phase of gastric acid secretion, vagally mediated synchronous
      stimulation of bicarbonate provides protection against the acid. The purpose of
      this study was to determine simultaneously the effect of electrical vagal
      stimulation (EVS) on pancreatic, hepatic, and duodenal mucosal bicarbonate
      secretion, thereby estimating their relative importance in vagally induced
      duodenal acid neutralization. Splanchnicotomy increased vagally induced
      pancreaticobiliary bicarbonate secretion, whereas duodenal mucosal bicarbonate
      secretion was unchanged. After splanchnicotomy, EVS (10 ms, 15 mA, 12 Hz)
      significantly increased pancreatic bicarbonate secretion (0-4.17 mmol/h), hepatic
      bicarbonate secretion (0.16 to 0.22 mmol/h), and duodenal mucosal bicarbonate
      secretion (0.17 to 0.31 mmol/h). Pancreaticobiliary bicarbonate secretion was
      atropine resistant, whereas vagally induced duodenal mucosal bicarbonate
      secretion was diminished by atropine (2.0 mg/kg). After splanchnicotomy, EVS (10
      ms, 15 mA, 12 Hz) had no effect on portal plasma concentration of secretin,
      whereas vasoactive intestinal peptide was increased (14-29 pM). EVS at 12 Hz with
      varying duration (3 or 10 ms) and amplitude (3-50 mA) had no further effect on
      the bicarbonate secretion from the three organs. In addition, biliary
      [14C]mannitol clearance was shown not to be a reliable marker of canalicular bile
      secretion in pigs. These results suggest that in the anesthetized pig 1) vagal
      stimulation is only of minor importance to hepatic bicarbonate secretion; 2)
      vagal stimulation activates pancreatic bicarbonate secretion through both
      cholinergic muscarinic and noncholinergic transmission; and 3) vagal stimulation
      induces duodenal mucosal bicarbonate secretion mainly through cholinergic
      muscarinic transmission. In conclusion, these results suggest that only
      pancreatic and duodenal bicarbonate production play a role in vagally induced
      duodenal acid neutralization.

PMID- 9038890
TI  - Functional heterogeneity of parietal cells along the pit-gland axis.
AB  - The gastric epithelium forms numerous short pits continuous with long tubular
      glands divisible into isthmus neck, and base regions. Parietal cells are produced
      in the isthmus and migrate down to the neck and base regions as they mature and
      age. Stimulation of parietal cells is manifested by translocation of H(+)-K(+)
      adenosinetriphosphatase-rich tubulovesicles (TV) from the cytoplasm into the
      secretory-apical (SA) membrane. In this study we used rabbit isolated gastric
      glands to examine the physiological responses of parietal cells to graded levels
      of stimulation. Quantitative morphometry was used to evaluate parietal cell
      response along the longitudinal axis of the gland. Acid secretion as estimated by
      [14C]aminopyrine uptake was well correlated with parallel enzymatic and
      immunoblot assays for the redistribution of H(+)-K(+)-ATPase from TV to SA
      membranes. These responses also correlated well with morphological
      transformations of parietal cells within the isthmus and neck regions of the
      gastric gland; however, parietal cells in the base of the gland showed very
      little morphological change in response to any of the stimuli used. The poor
      responsiveness of basal parietal cells is in agreement with observations of
      intact mucosa and suggests that older parietal cells may serve some function
      other than acid secretion.

PMID- 9038891
TI  - Characterization of two distinct chloride channels in cultured dog pancreatic
      duct epithelial cells.
AB  - Cl- secretion by pancreatic duct epithelial cells (PDEC) regulates cellular HCO3-
      secretion, an important component of the exocrine pancreas. In cystic fibrosis,
      for example, impaired function of the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl- channel results in decreased pancreatic secretion and
      secondary pancreatic insufficiency. Studies of ion transport by PDEC have been
      hindered by the lack of a practical in vitro model. We have successfully cultured
      nontransformed dog PDEC on Vitrogen-coated permeable membranes overlying a feeder
      layer of myofibroblasts and report the characterization of Cl- channels in these
      cells. Cl- conductance, assessed through efflux of 125I from PDEC, was stimulated
      by agents acting via adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic
      Ca2+. The Cl- conductances activated by cAMP and Ca2+ were distinct, since they
      were differentially inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
      and, to a lesser extent, by 5-nitro-2-(3-phenylpropylamino)benzoic acid and
      diphenylamine-2 carboxylate. Patch-clamp studies confirmed the presence of Cl-
      channels activated by cAMP and Ca2+, with differential inhibition by 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid. The presence of CFTR Cl- channels in
      PDEC was confirmed by immunoblotting. These cultured PDEC are an optimal model
      for studies of pancreatic duct secretion.

PMID- 9038892
TI  - Intestinal anaphylaxis induces Fos immunoreactivity in myenteric plexus of rat
      small intestine.
AB  - Fos immunohistochemistry was used to identify myenteric neurons activated as a
      consequence of intestinal anaphylaxis in Hooded-Lister rats sensitized to egg
      albumin (EA 10 micrograms ip). After incubation in test solutions, or after in
      vivo challenge, jejunal tissues were processed for immunohistochemistry with an
      anti-Fos antibody (1:500, TF161). The neuronal identity of the Fos-labeled nuclei
      was confirmed by double labeling with neuron-specific enclose (1:1,000). In in
      vitro studies, exposure of control tissue to 50 mM K(+)-Krebs-EA (2 x 10(-5) M)
      solutions significantly increased Fos immunoreactivity in the myenteric plexus,
      whereas a basal level of Fos was seen in control tissue incubated in Krebs
      solution, sham-sensitized tissue exposed to bovine serum albumin (BSA, 2 x 10(-5)
      M), or EA and sensitized tissue exposed to BSA. Pretreatment of sensitized tissue
      with doxantrazole (10(-4) M) markedly reduced Fos immunoreactivity observed after
      EA exposure. In in vivo studies, there was negligible Fos immunoreactivity in the
      myenteric plexus of control, sham-sensitized, or sensitized rats challenged with
      saline. A low level of Fos was seen in neurons of sham-sensitized rats challenged
      with BSA or EA and in sensitized rats challenged with BSA. Significantly greater
      levels of Fos were observed in the myenteric plexus of sensitized animals
      challenged with EA, even after pretreatment with capsaicin (125 mg/kg). These
      results suggest a role for myenteric neurons in intestinal anaphylaxis. In
      sensitized rats, activation of myenteric neurons is dependent on antigen-induced
      mast cell activation and occurs independently of capsaicin-sensitive afferent
      nerves.

PMID- 9038893
TI  - Relaxant effect of xenin on rat ileum is mediated by apamin-sensitive neurotensin
      type receptors.
AB  - The action of xenin, a novel 25-residue peptide of the neurotensin (NT)/xenopsin
      family, was investigated in isolated rat ileal muscle strips and in dispersed
      longitudinal smooth muscle cells of rat small intestine in vitro. Xenin relaxes
      KCl-precontracted ileal strips dose dependently (1 nM-3 microM). The order of
      potency of the investigated peptides was as follows: xenopsin = NT = xenin >
      neuromedin N. Kinetensin was inactive. Tetrodotoxin, hexamethonium,
      tetraethylammonium, 4-aminopyridine, and NG-nitro-L-arginine did not influence
      the relaxant effects of xenin or NT, whereas the K+ channel blocker apamin nearly
      abolished their effects. Desensitization against one of the peptides or blockade
      of NT receptors by SR-48692 prevented the effect of xenin and NT. Structure
      activity experiments revealed that the COOH-terminal part of the molecules of
      xenin and NT is essential for biological activity. Experiments with isolated
      dispersed smooth muscle cells and binding studies on intestinal smooth muscle
      cell membranes confirmed and extended the results obtained with muscle strips. In
      conclusion, xenin relaxes rat ileal smooth muscle via a muscular NT-type apamin
      sensitive receptor.

PMID- 9038894
TI  - Cryptdin gene expression in developing mouse small intestine.
AB  - In rodents, the four intestinal epithelial cell lineages differentiate and become
      morphologically distinct during the first 2-3 postnatal wk. In studies reported
      here, reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays
      detected Paneth cell defensin mRNAs in intestinal RNA from 1-day-old (P1) mice
      before crypt formation and maturation of the epithelium. Analysis of these
      defensin-coding RT-PCR products from P1 mice showed that 69% of clones sequenced
      coded for cryptdin-6, suggesting that it is the most abundant enteric defensin
      mRNA in the newborn. Paneth cell mRNAs, including cryptdins-4 and -5, lysozyme,
      matrilysin, and defensin-related sequences, also were detected in RNA from P1
      mouse intestine. Unlike adult mice, where only Paneth cells are immunopositive
      for cryptdin, cryptdin-containing cells were distributed throughout the newborn
      intestinal epithelium and not in association with rudimentary crypts. Cryptdin
      immunoreactivity in the P1 mouse intestine was specific for intracellular granule
      contents, and immunofluorescent detection of cryptdins on mucosal surfaces
      suggested that the peptides are released into the intestinal lumen in P1 mice
      Defensin secretion may contribute to innate immunity of the neonatal intestine
      before the presence of distinguishable Paneth cells.

PMID- 9038895
TI  - Nitric oxide inhibits calcium release from sarcoplasmic reticulum of porcine
      tracheal smooth muscle cells.
AB  - In the present study, effects of the nitric oxide donor, S-nitroso-N
      acetylpenicillamine (SNAP), on sarcoplasmic reticulum (SR) Ca2+ release were
      examined in freshly dissociated porcine tracheal smooth muscle (TSM) cells. Fura
      2-loaded TSM cells were imaged using video fluorescence microscopy. SR Ca2+
      release was induced by acetylcholine (ACh), which acts principally through
      inositol 1,4,5-trisphosphate (IP3) receptors, and by caffeine, which acts
      principally through ryanodine receptors (RyR). SNAP inhibited ACh-induced SR Ca2+
      release at both 0 and 2.5 mM extracellular Ca2+. Degraded SNAP had no effect on
      ACh-induced SR Ca2+ release. SNAP also inhibited caffeine-induced SR Ca2+
      release. ACh-induced Ca2+ influx was not affected by SNAP when SR reloading was
      blocked by thapsigargin. SNAP also did not affect SR Ca2+ reuptake. The membrane
      permeant analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromo-cGMP,
      mimicked the effects of SNAP. These results suggest that, in porcine TSM cells,
      SNAP reduces the intracellular Ca2+ response to ACh and caffeine by inhibiting SR
      Ca2+ release through both IP3 and RyR, but not by inhibiting influx or repletion
      of the SR Ca2+ stores. These effects are likely mediated via cGMP-dependent
      mechanisms.

PMID- 9038896
TI  - Origin and modulation of ACh release from rat airway cholinergic nerves.
AB  - The release of acetylcholine (ACh) from airway parasympathetic nerves was studied
      in rat trachea. We established stimulus parameters, examined the role of
      extracellular Ca2+, and investigated the origin of the released ACh by use of
      vesamicol, an inhibitor of ACh uptake in synaptic vesicles. The role of
      muscarinic autoreceptors and prostanoids on ACh release was also studied.
      Tracheal rings were incubated in Krebs-Henseleit solution containing neostigmine
      and guanethidine with or without atropine. ACh release was measured by high
      performance liquid chromatography with electrochemical detection. ACh release was
      dependent on frequency (0.5-16 Hz), voltage (10-25 V), and pulse duration (0.5-4
      ms). At 4 Hz, one-fifth of electrical field stimulation-induced ACh release was
      extracellular Ca2+ independent and vesamicol resistant, indicating its
      nonvesicular origin. Three-fifths were Ca2+ dependent and vesamicol sensitive,
      indicating that it was newly synthesized, and one-fifth was Ca2+ dependent but
      vesamicol resistant, indicating its origin from prestored vesicles. At 16 Hz, two
      fifths were nonvesicular and three-fifths were newly synthesized. Blockade of the
      muscarinic autoreceptor by atropine potentiated the release of ACh four- to
      fivefold. Neither of the cyclooxygenase inhibitors indomethacin or meclofenamate
      nor exogenous prostaglandin E2 affected ACh release, indicating that inhibitory
      prostanoids do not modulate ACh release.

PMID- 9038897
TI  - Lipopolysaccharide-induced goblet cell hypersecretion in the guinea pig trachea:
      inhibition by macrolides.
AB  - We studied the effects of macrolides on lipopolysaccharide (LPS)-induced airway
      goblet cell secretion in the guinea pig trachea. The goblet cell secretion was
      assessed in histological sections of the tracheal mucosa stained with alcian blue
      and periodic acid Schiff by arbitrarily determining mucus score, which is
      inversely related to the magnitude of mucus discharge. Inhalation of Escherichia
      coli LPS (5 mg/kg) caused a time-dependent decrease in mucus score, with the
      maximal response being from 542 +/- 49 to 92 +/- 20 arbitrary units (P < 0.001)
      after 3 h, which was accompanied by an increase in the number of neutrophils in
      the tracheal mucosa. The LPS-induced mucus discharge was inhibited by oral
      clarithromycin and erythromycin in a dose-dependent manner (5 and 10 mg/kg),
      whereas amoxicillin and cefaclor had no effect. Each dose of clarithromycin and
      erythromycin, but not amoxicillin or cefaclor, likewise attenuated the LPS
      induced recruitment of neutrophils. These results suggest that LPS stimulates
      goblet cell secretion and neutrophil accumulation in the airways and that
      macrolides may be of value in protecting against neutrophil-associated airway
      hypersecretion.

PMID- 9038898
TI  - Strain increases airway smooth muscle contractile and cytoskeletal proteins in
      vitro.
AB  - Mechanical stress contributes to lung development and the progression of some
      lung diseases, although its effects on individual lung cells are unknown. Because
      increased airway smooth muscle (ASM) is found in lung diseases where abnormal
      stress is present, we determined if strain (change in resting length) causes ASM
      hypertrophy independently of other in vivo influences. Cultured canine ASM cells
      were subjected to two levels of cyclic deformational strain for 14 days and
      compared with nonstrained cells by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and Western blotting. Cells subjected to 16-30% strain
      demonstrated increases in total cellular protein, myosin, myosin light chain
      kinase (MLCK), and desmin, whereas the cellular contents of actin, vimentin, and
      tubulin were similar. Changes in myosin appeared mostly due to the smooth muscle
      isoform, whereas nonmuscle myosin was unchanged. The increases in myosin and MLCK
      were disproportionate to increases in total protein, suggesting selective changes
      in contractile proteins. These relative increases in content of proteins were not
      as pronounced with 0-16% strain, suggesting a graded response. These data suggest
      that strain per se can increase the contractile proteins of ASM cells
      independently of other in vivo factors and modulates cultured cell phenotype to a
      more differentiated state, since it increases smooth muscle-specific proteins,
      such as smooth muscle myosin isoforms and desmin.

PMID- 9038899
TI  - Cell-matrix and cell-cell interactions modulate apoptosis of bronchial epithelial
      cells.
AB  - Apoptosis is an important process maintaining cell number and tissue structure.
      To determine whether cell-extracellular matrix (ECM) and cell-cell interactions
      modulate apoptosis in bronchial epithelium, we cultured human bronchial
      epithelial cells in different conditions and evaluated the cells for apoptosis.
      We found that plating cells in conditions that prevent cell-ECM adhesion induced
      apoptosis. Plating cells on type I collagen, fibronectin, and biosynthesized
      matrix prevented apoptosis, due at least in part to integrin-mediated adhesion.
      When cells were cultured at high density but under conditions preventing cell
      substratum adhesion, aggregation occurred. Apoptosis was inversely correlated
      with aggregation. Cell-cell adhesion in these conditions was mediated at least
      partly by integrins containing alpha v. Cell aggregation was not associated with
      activation of a signaling pathway that is usually activated by cell-ECM adhesion,
      phosphorylation of focal adhesion kinase, but was associated with Bcl-2 protein
      expression, consistent with the concept that Bcl-2 protects against apoptosis. We
      conclude that both cell-ECM and cell-cell interactions, likely mediated in part
      by integrins, modulate apoptosis in bronchial epithelium.

PMID- 9038900
TI  - Glucosylation of small GTP-binding Rho proteins disrupts endothelial barrier
      function.
AB  - The endothelial cytoskeleton is important for the regulation of endothelial
      barrier function. Small GTP-binding Rho proteins play a central role in the
      organization of the microfilament system. Clostridium difficile toxin B (TcdB)
      inactivates Rho proteins by glucosylation at Thr-37. We used TcdB as a probe to
      study the role of Rho proteins in the regulation of endothelial barrier function.
      TcdB time (50-170 min) and dose (10-100 ng/ml) dependently increased the
      hydraulic conductivity of cultured porcine pulmonary artery endothelial cell
      monolayers approximately 10-fold. Simultaneously, the albumin reflection
      coefficient decreased substantially from 0.8 to 0.15. Before endothelial
      hyperpermeability, TcdB reduced F-actin content in a dose-dependent manner,
      whereas G-actin content remained unchanged. Finally, we proved that TcdB caused
      dose (5-100 ng/ml)- and time-dependent glucosylation of Rho proteins in
      endothelial cells. Phalloidin, which stabilizes filamentous actin, prevented the
      effect of TcdB on endothelial permeability. In contrast to thrombin-, hydrogen
      peroxide-, or Escherichia coli hemolysin-induced hyperpermeability, the elevation
      of cyclic nucleotides did not block TcdB-related permeability. The data
      demonstrate a central role of small GTP-binding Rho proteins for the control of
      endothelial barrier function.

PMID- 9038901
TI  - Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery
      smooth muscle cells.
AB  - Nitric oxide (NO) is a potent endothelium-derived pulmonary vasodilator.
      Serotonin (5-HT; 10-50 microM) constricts pulmonary artery (PA) by releasing Ca2+
      from intracellular stores and promoting Ca2+ influx through Ca2+ channels in PA
      smooth muscle cells (PASMC). The effect of NO on 5-HT-induced increase in
      cytosolic free Ca2+ concentration ([Ca2+]i) in rat PASMC was investigated to
      elucidate whether inhibition of agonist-mediated Ca2+ rise is involved in the NO
      mediated pulmonary vasodilation. The 5-HT-induced increase in [Ca2+]i was
      characterized by a transient (because of Ca2+ release from intracellular stores)
      followed by a plateau (because of Ca2+ influx). Removal of extracellular Ca2+
      eliminated the 5-HT-induced [Ca2+]i plateau, but insignificantly affected the
      [Ca2+]i transient. In some of the PASMC bathed in the Ca(2+)-containing or Ca(2+)
      free solution, 5-HT also induced Ca2+ oscillations. Pretreatment of the cells
      with 10 microM cyclopiazonic acid (CPA) abolished, whereas 10 mM caffeine
      negligibly affected, the 5-HT-induced [Ca2+]i transients in the absence of
      external Ca2+. Authentic NO (approximately 0.3 microM) reversibly diminished 5-HT
      induced [Ca2+]i transients but augmented CPA-induced Ca2+ release in the absence
      of extracellular Ca2+. NO also significantly inhibited 5-HT-induced [Ca2+]i
      plateau in PASMC bathed in Ca(2+)-containing solution, suggesting that NO
      inhibits both agonist-induced Ca2+ release from the CPA-sensitive Ca2+ stores and
      Ca2+ influx from extracellular fluid. These data suggest that NO-induced
      inhibition of the evoked increases in [Ca2+]i and augmentation of Ca2+
      sequestration into intracellular stores in PASMC are involved in the mechanisms
      by which NO causes pulmonary vasodilation.

PMID- 9038903
TI  - Temporal changes in expression of TGF-beta isoforms in mouse lung exposed to
      oxygen.
AB  - Oxygen-induced pulmonary injury is associated with cell death and a significant
      inflammatory response. Because transforming growth factor (TGF)-beta is a potent
      modulator of the immune response, changes in expression of the three TGF-beta
      (beta 1, beta 2, beta 3) isoforms was determined in lungs of adult mice exposed
      to > 95% oxygen. TGF-beta 1 immunostaining within cuboidal nonciliated
      bronchiolar epithelial cells was increased within 3 h of oxygen exposure and
      continued to increase for 48 h before decreasing to control levels by 72 h. A
      similar but less marked change that was morphologically consistent with alveolar
      type II cells was observed in granulated cells. Immunostaining for TGF-beta 2 and
      TGF-beta 3 revealed a similar change in bronchiolar epithelium with little change
      observed in the alveolar epithelium. Immunohistochemical changes in TGF-beta
      expression were not observed in any other pulmonary cells. Northern blot analysis
      of total lung RNA revealed that expression of the TGF-beta mRNA was not markedly
      altered over the 72-h exposure period. Exposure to > 95% oxygen resulted in cell
      type-specific posttranscriptional changes in TGF-beta isoforms in the lung.

PMID- 9038902
TI  - Cytosolic Ca2+ and adenylyl cyclase responses in phenotypically distinct
      pulmonary endothelial cells.
AB  - Pulmonary microvascular endothelium forms a tighter barrier than does pulmonary
      artery endothelium; the mechanism of this important phenotypic difference is
      uncertain. We examined two regulators of endothelial permeability, cytosolic Ca2+
      concentration ([Ca2+]i) and adenosine 3',5'-cyclic monophosphate (cAMP), in
      microvascular (PMVEC) and pulmonary conduit artery (PAEC) endothelium. Both
      resting and stimulated [Ca2+]i were lower in PMVEC compared with PAEC (resting
      [Ca2+]i, 94 +/- 7 vs. 123 +/- 8 nM; ATP-stimulated peak, 1.04 +/- 0.14 vs. 1.98
      +/- 0.13 microM). Sustained Ca2+ transients in response to either ATP or
      thapsigargin were reduced in PMVEC compared with PAEC (ATP, 199 +/- 22 vs. 411 +/
      43 nM; thapsigargin, 195 +/- 13 vs. 527 +/- 65 nM), suggesting reduced Ca2+
      influx in PMVEC. Reduced Ca2+ influx in PMVEC was confirmed by Mn2+ quenching and
      patch-clamp experiments. mRNA for Ca(2+)-inhibitable and protein kinase C
      stimulated adenylyl cyclases was detected in both cell types. Whereas ATP caused
      a [Ca2+]i-mediated decrease in cAMP in PAEC, ATP caused a protein kinase C
      mediated increase in cAMP in PMVEC. We conclude that PMVEC express a unique
      phenotype that favors enhanced barrier function through attenuated Ca2+ influx
      and preservation of cAMP content.

PMID- 9038904
TI  - Site of methacholine reactivity in the peripheral airways: analysis using lung
      explants.
AB  - We used a recently developed lung explant technique to investigate the
      partitioning of airway contractility in the bronchioles of normoresponsive and
      hyperresponsive rats. Specifically, we addressed the questions 1) whether airway
      response to methacholine varied with airway size and 2) whether airways from rats
      known to be innately hyperresponsive to methacholine (Fisher) would have
      responses different from normoresponsive rats (Sprague-Dawley). We found that, in
      both strains of rats, contraction to methacholine occurred primarily in the
      medium- and larger-sized bronchioles (airways of diameter > 0.32 mm) and that, at
      the higher methacholine concentrations, the Fisher rats had greater degrees of
      contraction than did the Sprague-Dawley rats. These results suggest that the
      increased airway responsiveness seen in Fisher rats is due to an intrinsic
      increase in responsiveness (increased contractility) of their airways, which may
      be related to amount of smooth muscle, rather than an increase in airway
      sensitivity to methacholine. They do not, however, completely rule out the
      possibility of in vivo species-dependent differences in airway-parenchymal
      interactions.

PMID- 9038905
TI  - Mouse strain differences in ozone dosimetry and body temperature changes.
AB  - Strain differences in susceptibility to inhaled ozone (O3) have been observed in
      mice, with C57BL/6J (B6) mice reported to be more sensitive than C3H/HEJ (C3)
      mice when exposed to equal concentrations of O3. To determine whether differences
      in the delivered dose of O3 to the lung could help explain these differences, C3
      and B6 mice were exposed to 18O-labeled ozone (18O3), and the resulting 18O
      concentrations in pulmonary tissues were monitored as an indicator of O3
      delivered dose. Body core temperatures (Tco) of similarly treated mice were
      measured during O3 exposures (using surgically implanted temperature probes) in
      an effort to correlate lung O3 dose to changes in basal metabolism. Immediately
      after exposure to 18O3, C3 mice had 46% less 18O (per mg dry wt) in lungs and 61%
      less in tracheas than B6 mice. Nasal 18O tended to be lower in the C3 mice, but
      these differences were not significant. Although both strains responded to the O3
      exposure with significant decreases in Tco, C3 mice had a 70% greater mean
      temperature x time product decrease during the exposure than B6 mice. These
      results suggest that the strain differences in O3 susceptibility may be due to
      differences in O3 dose to the lung, which may be related to differences in the
      ability of the mice to lower their Tco in response to O3 exposure.

PMID- 9038906
TI  - Role of membrane potential in hypoxic inhibition of L-arginine uptake by lung
      endothelial cells.
AB  - System y+ accounts for the majority of L-arginine transport by pulmonary artery
      endothelial cells (PAEC). Given that membrane potential is a driving force for
      transport via system y+, we examined the hypothesis that hypoxia inhibits this
      transport by decreasing membrane potential. Porcine PAEC or plasma membrane
      vesicles derived from these cells were exposed to normoxia (room air-5% CO2) or
      hypoxia (0% O2-95% N2-5% CO2). After exposure, L-[3H]arginine transport and/or
      accumulation of the lipophilic cation [3H]tetraphenylphosphonium, a quantitative
      sensor of changes in cell membrane potential, were measured. Hypoxia caused
      reversible time-dependent decrease in L-arginine transport and membrane potential
      in PAEC and in plasma membrane vesicles. Comparable decreases in membrane
      potential and L-arginine transport by PAEC were also observed after
      depolarization induced by KCl or ouabain. Hyperpolarization, induced by
      valinomycin, increased membrane potential and L-arginine transport in PAEC and
      plasma membrane vesicles. Valinomycin also prevented the hypoxia-mediated
      decreases in membrane potential and L-arginine transport in PAEC. These results
      indicate that hypoxia-induced plasma membrane depolarization is responsible for
      reduced L-arginine transport by system y+ in hypoxic porcine PAEC.

PMID- 9038907
TI  - Identification of Na(+)-K(+)-ATPase beta-subunit in alveolar epithelial cells.
AB  - The Na(+)-K(+)-ATPase is a heterodimeric plasma membrane protein that consists of
      a catalytic alpha-subunit and a smaller glycosylated beta-subunit that has not
      been fully characterized in alveolar epithelial cells (AEC) to date. In this
      study, we identified the Na(+)-K(+)-ATPase beta-subunit protein in rat AEC and
      lung membranes using immunochemical techniques. Rat AEC grown in primary culture
      and rat lung, brain, and kidney membranes were solubilized in either 2% sodium
      dodecyl sulfate (SDS) sample buffer for SDS-polyacrylamide gel electrophoresis or
      in 1% Nonidet P-40 lysis buffer for immunoprecipitation studies. Na(+)-K(+)
      ATPase beta-subunit was not detected in either AEC or lung membranes on Western
      blots when probed with a panel of antibodies (Ab) against beta-subunit isoforms,
      whereas brain and kidney beta-subunit were recognized as broad approximately 50
      kDa bands. AEC, lung, and kidney membranes were immunoprecipitated with anti-beta
      Ab IEC 1/48, a monoclonal Ab that recognizes beta-subunit protein only in its
      undenatured state. The beta-subunit was detected in the immunoprecipitate (IP)
      from kidney membranes by several different anti-beta-subunit Ab. The beta-subunit
      was faintly detectable from AEC and lung IP as a broad approximately 50-kDa band
      when blotted with the polyclonal anti-beta 1-subunit Ab SpET but could not be
      detected by blotting with other anti-beta Ab. Treatment of the IP from kidney,
      lung, and AEC with N-glycosidase F for 2 h at 37 degrees C resulted in
      immunodetection of identical approximately 35 kDa bands when probed with all anti
      beta 1 Ab on Western blots. From these results, we conclude that rat lung and AEC
      possess immunoreactive beta-subunit protein that is only readily detectable after
      deglycosylation. Because anti-beta Ab fail to detect the Na(+)-K(+)-ATPase beta
      subunit in rat lung or AEC by standard Western blotting techniques under the
      conditions of these experiments, our results suggest that lung beta-subunit may
      be glycosylated differently from kidney and other tissues. These differences
      appear to be due to organ- or cell-specific posttranslational processing of the
      beta 1-subunit and may result in altered regulation of sodium pumps in lung
      compared with other epithelia.

PMID- 9038908
TI  - Effects of mechanical factors on growth and maturation of the lung in fetal
      sheep.
AB  - Previous fetal studies indicated that endocrine factors control surfactant
      maturation, whereas mechanical forces affect lung growth, but not surfactant. We
      altered mechanical forces in fetal sheep lungs at 100-108 days gestation by
      tracheal ligation (TL, n = 15, 7 successful studies) to accelerate lung growth,
      transection of cervical spinal cord (TCSC, n = 17, 6 successful studies) to
      produce lung hypoplasia, or sham operation (n = 11, 6 successful studies). The
      reasons for the high mortality rates are not known. At delivery (130-142 days),
      groups were similar in gestational age, weight, and cortisol. Effects on lung
      growth were similar to, but effects on surfactant differed from, previous
      reports. TL increased lung growth but decreased saturated phosphatidylcholine
      (SatPC) and surfactant protein (SP)A and apparently decreased SP-B and relative
      numbers of alveolar type II cells (based on immunohistochemical studies of 1
      animal in each group); TCSC had opposite effects. In contrast to a previous study
      (J. A. Kitterman, G. C. Liggins, G. A. Campos, J. A. Clements, C. S. Forster, C.
      H. Lee, and R. K. Creasy, J. Appl. Physiol, 51: 384-390, 1981), SatPC did not
      correlate with cortisol. We conclude that altering mechanical forces in fetal
      lung affects not only lung growth but also surfactant maturation and possibly
      alveolar epithelial differentiation and disturbs the normal correlation between
      cortisol and surfactant. Associated changes in insulin-like growth factor I (IGF
      I; increased by TL, P = 0.003) suggest a possible role for IGF-I in these
      effects.

PMID- 9038909
TI  - Effect of lowering serum cholesterol on the composition of surfactant in adult
      rat lung.
AB  - Treatment of rats with 10 mg.kg body wt-1 day-1 4-aminopyrazolo[3,4-d]pyrimidine
      (APP) for 2 days markedly reduced serum cholesterol and phospholipids. This was
      associated with large decreases in the principal component of alveolar
      surfactant, the disaturated phospholipids (DSP), in the lamellar body and in the
      tubular myelin-rich and -poor alveolar fractions, but with no concomitant change
      in cholesterol or surfactant protein A. These decreases in DSP were associated
      with a decrease in the synthesis of surfactant phospholipids. Despite these large
      changes in composition of alveolar surfactant, we could detect no change in
      either static or dynamic lung compliance. However, the treatment markedly
      increased both the minimum and maximum surface tension of the lipid extract of
      the tubular myelin-rich fraction, as measured by bubble surfactometry. Whereas
      these changes appeared unimportant in the isolated perfused lung at resting tidal
      volume, they were associated with edema after an increase in tidal volume. The
      ability of APP to inhibit phospholipid synthesis selectively makes it a useful
      tool in investigating the surfactant system.

PMID- 9038910
TI  - Phosphorylation of calponin in airway smooth muscle.
AB  - Calponin is an actin-binding protein known to be a substrate in vitro for several
      protein kinases and phosphoprotein phosphatases. We tested the hypothesis that
      calponin is phosphorylated in vivo using canine tracheal smooth muscle strips
      metabolically labeled with 32Pi. Calponin was gel purified from muscles
      stimulated with 1 microM carbachol. Phosphorylation increased to 2.0 times the
      basal level of 178 +/- 26 counts per minute (cpm)/microgram calponin within 30 s
      to 350 +/- 64 cpm/micrograms. Two-dimensional nonequilibrium pH gradient gel
      electrophoresis resolved four charge isoforms of calponin in unstimulated muscle.
      Stimulation with carbachol induced an additional more acidic isoform.
      Phosphorylation of calponin in vitro with protein kinase C (PKC) also induced
      formation of additional acidic isoforms. The functional effect of phosphorylation
      was demonstrated using an in vitro motility assay in which unphosphorylated
      calponin (2 microM) caused a profound inhibition of actin sliding. Calponin
      phosphorylated by PKC did not inhibit actin sliding. The results show that
      phosphorylation of calponin occurs in intact tracheal smooth muscle and that
      phosphorylation of calponin in vitro alleviates the inhibitory effect of calponin
      on actomyosin function.

PMID- 9038911
TI  - Acute and chronic effects of allergic airway inflammation on pulmonary nitric
      oxide production.
AB  - Nitric oxide (NO) is thought to be an important modulator of airway function in
      normal and inflamed airways. We investigated the acute and chronic effects of
      induced allergic airway inflammation on NO levels in mixed expired gas and NO
      synthase (NOS) expression in guinea pigs and the relationship between airway
      responses and NO production. Airway inflammation was induced by repeated
      aerosolized antigen exposure, and its presence was confirmed by bronchoalveolar
      lavage. Acute antigen exposure in sensitized animals produced a fivefold increase
      in respiratory resistance over baseline that was associated with a cotemporal
      increase in expired NO (17 +/- 1 to 56 +/- 8 parts per billion, P < 0.01). A
      continuous subcutaneous infusion of nitro-L-arginine methyl ester (L-NAME), a
      competitive inhibitor of NOS, markedly decreased expired NO (P < 0.01) and
      resulted in a significantly greater rise in resistance following antigen
      challenge (660 +/- 60 vs. 497 +/- 42% of baseline in non-L-NAME-treated animals,
      P < 0.05). These data support the hypothesis that endogenous pulmonary NO
      production, as reflected by expired NO, has an important homeostatic role in
      acute allergic bronchoconstriction.

PMID- 9038912
TI  - Selective and transient in vitro effects of heat shock on alveolar type II cell
      gene expression.
AB  - The heat shock response is a highly conserved stress response that can
      transiently inhibit non-heat shock protein gene expression. Although heat shock
      protects against acute lung injury, its effects on lung cell gene expression are
      not known. We studied the in vitro effects of heat shock on the expression of
      several genes important to alveolar type II cells. Prior induction of heat shock
      transiently inhibited cytokine-mediated inducible nitric oxide synthase gene
      expression and cytokine-mediated manganese-superoxide dismutase mRNA expression
      in murine lung epithelium. In contrast, heat shock had no effect on expression of
      surfactant protein (SP) A or B mRNA, or SP-B peptide synthesis. Cell survival
      studies indicated that the inhibitory effects were not secondary to cytotoxicity.
      Previous heat shock also modestly enhanced the ability of cells to withstand
      oxidant stress. We conclude that in vitro heat shock has selective and transient
      inhibitory effects on alveolar type II cell gene expression. Transient inhibition
      of cytokine-inducible genes, with concomitant conservation of genes required for
      normal respiratory function (SP) may explain, in part, the mechanism by which
      heat shock protects during acute lung injury.

PMID- 9038913
TI  - Lung capillary changes in hepatic cirrhosis in rats.
AB  - The hypoxemia of the hepatopulmonary syndrome may result from dilated
      intrapulmonary vascular segments. Knowledge of the size, density, and branching
      frequency of the lung capillaries might confirm this hypothesis and suggest that
      the pathogenesis may involve vascular dilatation or angiogenesis. To investigate
      these changes, the common bile duct of rats was tied off to cause biliary
      cirrhosis. Later (4 wk), the pulmonary vasculature of these animals was cast, and
      the casts were studied with scanning electron microscopy. In the ligated animals,
      evidence for enhancement of the bronchial to pulmonary circulation was found:
      cast vasa vasorum of the pulmonary arteries and cast bronchial veins emptying
      into pulmonary veins. Ligated animals had more adherent intracapillary cells per
      alveolus than the sham-operated animals. The diameters of all capillary beds were
      larger in the ligated animals. The alveolar capillary density was increased, but
      the branching frequency was not. A few areas suggesting angiogenesis were found.
      Induction of biliary cirrhosis enhances the pulmonary-systemic circulation,
      increases intracapillary adherent cells, capillary diameter, and density, and may
      be associated with angiogenesis.

PMID- 9038914
TI  - Decreased Cu,Zn-SOD activity in asthmatic airway epithelium: correction by
      inhaled corticosteroid in vivo.
AB  - To investigate the antioxidant response of respiratory epithelium to the chronic
      airway inflammation in asthma, the major intracellular antioxidants [copper and
      zinc-containing superoxide dismutase (Cu,Zn-SOD) and manganese-containing SOD (Mn
      SOD), catalase, and glutathione peroxidase] were quantitated in bronchial
      epithelial cells of healthy control and asthmatic individuals. Although catalase
      and glutathione peroxidase in bronchial epithelium of asthmatics were similar to
      control SOD activity in asthmatics not on inhaled corticosteroid (-CS) was lower
      than asthmatics on inhaled corticosteroid (+CS) and controls. Investigation of Mn
      SOD and Cu,Zn-SOD activities revealed that the lower SOD activity in asthmatics 
      CS was because of decreased Cu,Zn-SOD activity. However, Mn-SOD and Cu,Zn-SOD
      mRNA and protein levels were similar among asthmatics -CS, asthmatics +CS, and
      controls. Importantly, Cu,Zn-SOD specific activity in asthmatics -CS was
      decreased in comparison with control and asthmatics +CS. Furthermore, in paired
      comparisons of asthmatics -CS and +CS, inhaled corticosteroids resulted in
      normalization of bronchial epithelial Cu,Zn-SOD specific activity. These findings
      suggest loss of Cu,Zn-SOD activity in asthma is related to inflammation, perhaps
      through oxidant inactivation of Cu,Zn-SOD protein.

PMID- 9038915
TI  - Endothelial gaps: time course of formation and closure in inflamed venules of
      rats.
AB  - In the rat trachea, substance P causes rapid but transient plasma leakage. We
      sought to determine how closely the number, morphology, and size of endothelial
      gaps correspond to the time course of this leakage. Endothelial gaps were
      examined by scanning electron microscopy (EM), by transmission EM, or by light
      microscopy after silver nitrate staining. Substance P-induced leakage of the
      particulate tracer Monastral blue peaked at 1 min but decreased with a half-life
      of 0.3 min. The number of silver-stained gaps also peaked at 1 min then decreased
      significantly more slowly (half-life 1.9 min) than the leakage. Scanning EM
      revealed two types of endothelial gaps, designated vertical gaps and oblique
      slits. Vertical gaps predominated at peak leakage, whereas oblique slits became
      more common as the leakage diminished. Measurements of the mean diameter of
      vertical gaps made by light microscopy, scanning EM, and transmission EM were all
      in the range of 0.36-0.47 micron. Fingerlike endothelial cell processes that
      appeared during gap formation became shorter as the leakage diminished (mean
      length: 1.44 microns at 1 min compared with 1.06 microns at 3 min after substance
      P), suggesting a role in gap closure. We conclude that the plasma leakage
      occurring immediately after an inflammatory stimulus results from the rapid
      formation of endothelial gaps. Multiple factors, including alterations in gap
      morphology, gap closure, and changes in driving force, are likely to participate
      in the rapid decrease in the leakage.

PMID- 9038916
TI  - Sodium effects on 4-aminopyridine-sensitive transient outward current in canine
      ventricular cells.
AB  - Tetrodotoxin (TTX) or substitution of external Na+ reduces the 4-aminopyridine
      sensitive transient outward current (Ito1) in rat ventricular myocytes. We
      investigated the outcome of reducing external sodium on the kinetics, gating, and
      selectivity of Ito1 with a dual-patch electrode technique to record whole cell
      currents and transmembrane potentials independently of the voltage clamp in
      canine midmyocardial cells. Steps from -80 to 0 mV produced overlapping inward
      sodium and outward potassium currents, accompanied by a loss of voltage control
      associated with activation of INa. Substitution of external Na+ or application of
      TTX abolished INa, restored voltage control, and reduced Ito1. Inactivation of
      INa with a 10-ms prestep to -45 mV decreased Ito1 to the same extent as external
      Na+ substitution. The kinetics, gating, and selectivity of Ito1 recorded after
      inactivation of INa were unaffected by drastic reductions in external Na+. Our
      findings suggest that a larger Ito1 in the presence of normal external Na+ is due
      to 1) transient loss of voltage control and concomitant changes in activation of
      Ito1 and/or 2) facilitation of an outward current by intracellular Na+. We
      conclude that reduction of external sodium has no direct effect on the kinetics
      or gating of Ito1, non does Na+ contribute to current flow through Ito1 channels
      in canine midmyocardial cells.

PMID- 9038917
TI  - Contractile actions of C5a on isolated porcine coronary resistance and
      conductance arteries.
AB  - The comparative effects of the complement component C5a on coronary resistance
      and conductance arteries have not been evaluated. To clarify the coronary
      contractile actions of this anaphylatoxin, we studied the effects of C5a on
      development of isometric tension in isolated porcine coronary conductance and
      resistance arteries. Internal diameters of conductance and resistance vessels
      were 367 +/- 21 and 88 +/- 4 microns, respectively. Vessel ring segments were
      suspended in a microvessel myograph, stretched to the peaks of their length
      tension curves, and precontracted with 30 mM K+ physiological salt solution. Dose
      response curves to C5a (2, 10, and 50 nM) were obtained. At 50 nM, the C5a
      induced increase in tension in resistance arteries (4.1 +/- 0.9 to 5.7 +/- 1.4
      mN, 35.8 +/- 3.4%) was significantly greater (P < 0.05) than in conductance
      arteries (10.7 +/- 2.2 to 12.4 +/- 2.6 mN, 15.6 +/- 3.0%). A specific thromboxane
      A2 receptor antagonist, SQ-29548, virtually eliminated C5a-induced increases in
      tension. C5a did not impair endothelium-dependent relaxation in either
      conductance or resistance vessels, as indicated by the half-maximal effective
      dose (ED50) calculated from bradykinin dose-response curves before and after
      exposure of the vessels to 50 nM C5a (resistance: pre-C5a ED50 = 2 nM, post-C5a
      ED50 +/- 3 nM; conductance: pre-C5a ED50 +/- 13 nM, post-C5a ED50 +/- 14 nM).
      These results indicate that 1) C5a has a greater vasoconstrictive effect on
      isolated porcine resistance than conductance coronary arteries; 2) C5a-induced
      coronary constriction is mediated by thromboxane A2; and 3) C5a does not impair
      endothelium-dependent relaxation of isolated porcine coronary arteries.

PMID- 9038918
TI  - Lysophosphatidylcholine transduces Ca2+ signaling via the platelet-activating
      factor receptor in macrophages.
AB  - To clarify the molecular mechanism underlying the lysophosphatidylcholine (LPC)
      signaling, we studied the effect of LPC on the intracellular free calcium
      concentration ([Ca2+]i) in murine peritoneal macrophages. LPC when added alone
      induced biphasic elevation of [Ca2+]i, which consisted of a rapid increase
      followed by sustained elevation. LPC, when added with equimolar cholesterol,
      induced only the rapid increase in [Ca2+]i, which was blocked by WEB-2086, a
      selective platelet-activating factor (PAF) receptor antagonist. These results
      suggest LPC exerts a specific Ca2+ signaling. The sustained elevation reflected
      the cell lysis. Furthermore, we confirmed its pathway in a more specific manner
      using cloned PAF receptors expressed in Chinese hamster ovary cells. LPC induced
      an elevation of [Ca2+]i in a concentration-dependent manner only when the PAF
      receptor had been expressed, and the elevation of [Ca2+]i was blocked by WEB
      2086. Taken together, LPC transduces Ca2+ signaling via the PAF receptor.
      Activation of the PAF receptor by LPC may indicate its novel important role in
      the pathogenesis of atherosclerosis.

PMID- 9038919
TI  - Role of adenosine receptor subtypes in neural stunning of sympathetic coronary
      innervation.
AB  - Adenosine plays an important role in postischemic dysfunction of cardiac
      sympathetic nerves because exogenously infused adenosine produces and adenosine
      deaminase prevents "neural stunning." We examined whether adenosine acts via a
      specific receptor mechanism to produce neural stunning. Anesthetized dogs were
      treated with propranolol to attenuate increases in coronary flow due to
      adrenergic stimulation of myocardial metabolism. A 15-min occlusion of the left
      anterior descending coronary artery (LAD) attenuated subsequent LAD coronary
      vasoconstriction to bilateral sympathetic stimulation during reperfusion by 75%
      (P < 0.05). Coronary infusion of the adenosine-receptor antagonist 8-p
      sulfophenyltheophylline (nonspecific), 8-cyclopentyl-1,3-dipropylxanthine (A1
      specific), or 3,7-dimethyl-1-propagylxanthine (A2 specific) during LAD occlusion
      prevented the attenuation of sympathetic coronary constriction. In separate
      experiments, either the specific adenosine agonist N6-cyclopentyl-adenosine (A1
      specific) or CGS-21680 (A2 specific) or a combination of both agonists was
      infused into the LAD for 15 min. Neither agonist alone attenuated subsequent
      sympathetic coronary constriction. In contrast, 15 min after the combined
      administration of both agonists, sympathetic vasoconstriction was reduced. We
      conclude that adenosine is capable of attenuating neurogenic coronary
      constriction through a receptor-mediated mechanism. Activation of more than one
      receptor subtype is necessary to produce neural stunning.

PMID- 9038920
TI  - Cardiac inducible nitric oxide synthase negatively modulates myocardial function
      in cultured rat myocytes.
AB  - Recent work has demonstrated that endotoxin or cytokines induce nitric oxide
      synthase in heart or cardiac myocytes. We investigated the functional
      significance of inducible nitric oxide synthase (iNOS) in indo 1-loaded beating
      myocytes with regard to intracellular Ca2+ concentration ([Ca2+]i) and cell
      contraction. Lipopolysaccharide (LPS; 10 micrograms/ml) time dependently induced
      iNOS mRNA and protein in cultured neonatal rat cardiac myocytes. Nitrite
      concentration in the medium and intracellular guanosine 3',5'-cyclic
      monophosphate (cGMP) contents after 24-h exposure to LPS increased in proportion
      to the levels of iNOS induction in these cells. Myocytes treated with both NG
      monomethyl-L-arginine and LPS for 24 h expressed iNOS protein, but nitrite
      production was significantly inhibited. Subsequent perfusion with 100-fold molar
      excess L-arginine of these myocytes elicited decreases in peak systolic [Ca2+]i
      (790 +/- 42 to 551 +/- 27 nM, P < 0.05), relative amplitude of cell contraction
      (100 to 72.4 +/- 5.5%, P < 0.05), and spontaneous beating rate (146 +/- 13 to 85
      +/- 22 beats/min, P < 0.05). Pretreatment with methylene blue or KT-5823
      inhibited these negative myocardial effects. These results suggest that LPS
      induces iNOS in cardiac myocytes and that the increased nitric oxide produced by
      iNOS has cardiac depressant effects through the activation of cGMP-dependent
      protein kinase.

PMID- 9038921
TI  - c-Fos expression in the medulla induced by static muscle contraction in cats.
AB  - In this study, we examined Fos-like immunoreactivity (FLI) in the medulla after
      static muscle contraction induced by stimulation of L7 and S1 ventral roots of
      the spinal cord in anesthetized cats. The results show that FLI increases in the
      lateral reticular nucleus, nucleus of the solitary tract, lateral tegmental
      field, vestibular nucleus, subretrofacial nucleus, and A1 region of the medulla
      in comparison with these same areas in sham-operated animals (P < 0.05 in each
      region). In the rostral ventrolateral medulla, FLI distribution in neurons
      containing phenylethanolamine-N-methyltransferase (PNMT, the synthetic enzyme for
      epinephrine) was also observed utilizing double-labeling methods. The majority of
      neurons with PNMT also expressed FLI (66 +/- 4%). These data are in contrast to
      the results from sham-operated animals showing that 24 +/- 3% of the neurons
      costained with PNMT (P < 0.05). Our findings indicate that expression of FLI can
      be used to identify neurons activated during static muscle contraction and
      support previous studies implicating the ventrolateral medulla as a critical
      region for expression of the exercise pressor reflex. Furthermore, neurons in the
      rostral ventrolateral medulla containing PNMT were activated during static muscle
      contraction.

PMID- 9038922
TI  - Coordinate regulation of SR Ca(2+)-ATPase and phospholamban expression in
      developing murine heart.
AB  - Phospholamban, the regulator of Ca(2+)-adenosinetriphosphatase (ATPase) activity
      in cardiac sarcoplasmic reticulum (SR), is an important determinant of basal
      myocardial performance. To determine whether phospholamban expression is
      developmentally regulated in the mouse and whether such regulation reflects
      alterations in Ca2+ pump activity, hearts from different stages of development
      were processed for molecular biological and biochemical studies. Both
      phospholamban and Ca(2+)-ATPase mRNAs were approximately 40% of adult (100%)
      levels at birth and gradually increased to approach adult levels by day 15 of
      development. These changes in transcript levels were indicative of changes at the
      protein level for both phospholamban and Ca(2+)-ATPase. Analysis of the initial
      rates of Ca2+ uptake demonstrated that over the course of development the
      upregulation of Ca(2+)-ATPase correlated with increases in the maximal rates of
      Ca2+ uptake and the constant apparent stoichiometric ratio of phospholamban to
      Ca(2+)-ATPase correlated with maintenance of a constant affinity of this enzyme
      for Ca2+ (0.25 +/- 0.03 microM Ca2+). Furthermore, targeted ablation of
      phospholamban in the mouse resulted in a much higher affinity of Ca2+ uptake for
      Ca2+ (0.10 +/- 0.02 microM Ca2+) than that observed in wild-type hearts, and this
      increased affinity was also maintained across different stages of postnatal
      development. These findings suggest that phospholamban is a major regulator of
      the affinity of Ca(2+)-ATPase for Ca2+, and coordinate regulation of the
      expression levels of these two SR proteins may be necessary for maintaining Ca2+
      homeostasis in the developing mammalian heart.

PMID- 9038923
TI  - Mechanisms of coronary vasoconstriction induced by high arterial oxygen tension.
AB  - In isolated rabbit hearts perfused with suspension of red blood cells, we
      investigated the role of the endothelium and of several substances in the
      coronary vasoconstriction induced by a high arterial blood oxygen tension (PaO2).
      Red blood cells in Krebs-Henseleit buffer were oxygenated to obtain control and
      high-PaO2 perfusates. Arterial oxygen content was kept constant in both
      perfusates by reducing hemoglobin concentration in the high-PaO2 perfusate.
      Coronary blood flow was kept constant so that oxygen supply would not vary with
      the rise in PaO2. Increases in perfusion pressure therefore reflected increased
      coronary resistance. The high PaO2-induced coronary vasoconstriction was not
      affected by administration of indomethacin, nordihydroguaiaretic acid, NG-nitro-L
      arginine, or superoxide dismutase and catalase but was abolished after
      endothelium damage or by cromakalim. These results demonstrate that 1) the
      endothelium contributes to the high PaO2-induced coronary vasoconstriction; 2)
      this effect is independent of cyclooxygenase or lipoxygenase products, nitric
      oxide, or free radicals; and 3) the closure of ATP-sensitive K+ channels mediates
      this vasoconstriction.

PMID- 9038924
TI  - Exogenous opioids influence the microcirculation of injured peripheral nerves.
AB  - Local microvessels of peripheral nerve trunks (vasa nervorum) dilate following
      capsaicin-induced inflammation or local nerve trunk injury. In previous work, we
      observed that morphine blocked capsaicin-induced dilation of vasa nervorum
      presumably through the action of local opioid receptors. In the present work, we
      studied injury-related hyperemia of the rat sciatic vasa nervorum using laser
      Doppler and hydrogen clearance microelectrode measurements of local perfusion.
      Systemic morphine reversed hyperemia by vasoconstricting both extrinsic and
      intrinsic microvessels supplying 48-h-old "neuroma" preparations or crush zones
      of peripheral nerve trunks. Morphine did not constrict microvessels of
      contralateral uninjured or sham exposed but uninjured sciatic nerves. In contrast
      to the injured nerves, contralateral uninjured nerves exposed to morphine
      frequently had a rise in local perfusion, indicating vasodilation. The
      vasoconstrictive actions of morphine were blocked by pretreatment with naloxone
      and were not mimicked by saline injections alone. Systemic doses of selective
      opioid agonists to mu-, kappa-, and delta-receptors also selectively constricted
      microvessels of injured nerves. Local blood flow in older experimental neuromas
      at 7 days had partial sensitivity to morphine, whereas at 14 days perfusion flow
      was not influenced by morphine. Exogenous opioids dampen early but not later
      inflammatory microvasodilation and could have important influences on the nerve
      regenerative milieu.

PMID- 9038925
TI  - Purine nucleotides and phospholipids in ischemic and reperfused rat skeletal
      muscle: effect of ascorbate.
AB  - The effect of intravenously administered ascorbate on the ischemic and reperfused
      rat skeletal muscle was investigated. Purine nucleotides and phospholipids in
      skeletal muscle from rats subjected to 4 h of ischemia followed by 1-h
      reperfusion were analyzed by high-performance liquid chromatography. In addition,
      ATP, phosphocreatine (PCr), Pi, and phosphomonoesters (PME) were analyzed by 31P
      nuclear magnetic resonance at 202.4 MHz, and individual PME such as glucose-6
      phosphate and IMP were quantified. PCr and ATP were exhausted after 4 h of
      ischemia and recovered poorly upon reperfusion in the soleus and tibialis muscle
      of untreated rats. Postischemic reperfusion resulted in significant loss of
      cardiolipin. Treatment with 55 mM ascorbate resulted in total restoration of PCr
      during reperfusion, and ATP recovered to 42% of control in the soleus. Recovery
      was improved in the tibialis as well, and the cardiolipin decrease was limited. A
      lower ascorbate concentration (5 mM) did not enhance postischemic recovery. Our
      findings show that a high dose of ascorbate improves the energetic state of rat
      skeletal muscle during postischemic reperfusion, probably due to its antioxidant
      function.

PMID- 9038926
TI  - Dual role of cGMP in modulation of macromolecule permeability of aortic
      endothelial cells.
AB  - The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on cytosolic Ca2+
      dynamics and associated alterations in macromolecule permeability was
      investigated in cultured monolayers of aortic endothelial cells. Addition of the
      membrane-permeable cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate (8
      BrcGMP, 5 x 10(-4)M) or activators of the soluble (3-morpholinosydnonimine, 10(
      5) M) or the particulate guanylyl cyclase (atrial natriuretic peptide, 10(-7) M)
      to unstimulated monolayers led to a decrease in permeability (8-BreGMP: 62 +/- 8%
      of control) without affecting low basal cytosolic Ca2+ concentration ([Ca2+]i, 87
      +/- 8 nM). In contrast, under conditions of elevated [Ca2+]i (503 +/- 95 nM) and
      increased permeability (155 +/- 7% of control) induced by 10(-6) M ionomycin, 8
      BrcGMP, 3-morpholinosydnonimine, or atrial natriuretic peptide provoked a further
      increase in permeability (8-BrcGMP: 255 +/- 27%). These agents failed to increase
      permeability when added before or after the ionomycin-triggered transitory rise
      in [Ca2+]i. The increase in permeability in response to 8-BrcGMP was due to a
      secondary further rise in [Ca2+]i (758 +/- 87 nM), which was abolished in the
      absence of extracellular Ca2+, indicating influx of exogenous Ca2+ as the cause.
      Changes in [Ca2+]i and permeability were inhibited, in the presence of the Rp
      diastereomer of 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphothioate
      (2 x 10(-5) M), an inhibitor of the cGMP-dependent protein kinase. These findings
      show that, depending on [Ca2+]i, cGMP can play opposite roles in endothelial
      permeability in one and the same cell preparation.

PMID- 9038927
TI  - Mechanical stimulation is not responsible for activation of gastrointestinal
      afferents during ischemia.
AB  - Abdominal ischemia reflexly excites the cardiovascular system through activation
      of visceral sympathetic afferents. Although a number of ischemic metabolites are
      known to stimulate sympathetic afferents, the contribution of mechanical
      stimulation to activation of afferents during abdominal ischemia remains
      uncertain. Thus the present study examined the role of changes in motility in
      activation of gastrointestinal afferents during ischemia. Single-unit activity of
      C fiber afferents located on the stomach, duodenum, jejunum, or colon was
      recorded from the right sympathetic chain of anesthetized cats during 15 min of
      ischemia. Intraluminal pressure, as a reflection of local mechanical activity,
      was measured by an open catheter placed in the lumen of the gastrointestinal
      tract. The results show that gastrointestinal motility was mainly inhibited
      during abdominal ischemia. Changes in intraluminal pressure did not correlate
      with afferent discharge activity during ischemia (r = -0.32, n = 10).
      Furthermore, discharge frequency of gastrointestinal afferents during ischemia
      was not altered significantly by topical application of 100 micrograms/ml of
      atropine (3.98 +/- 0.62 to 3.83 +/- 0.59 imp/s, n = 12), which profoundly
      inhibited local gastrointestinal motility. Collectively, these data indicate that
      gastrointestinal motility changes during abdominal ischemia do not contribute to
      activation of gastrointestinal sympathetic C fiber afferents.

PMID- 9038928
TI  - Anisotropic repolarization in ventricular tissue.
AB  - Extracellular recording and stimulation techniques have been used to demonstrate
      that the effective refractory period of epicardial ventricular cells is
      significantly influenced by the sequence of activation. Whether myocardial fiber
      orientation is also important in determining the repolarization process is
      unclear. To determine the importance of fiber orientation on the repolarization
      process, we studied 12 blocks of pig right ventricular tissue in vitro. The size
      of each tissue block was 30 x 30 x 2 mm. Transmembrane action potentials were
      recorded, and effective refractory periods were measured from the preparation's
      epicardial surface, which showed nearly uniform fiber orientation. Tissues were
      paced at 500- and 1,000-ms cycle lengths. Sequential recordings were made at 1,
      4, 7, 10, 13, and 16 mm from the stimulation site along and across the fibers.
      The results show that propagation of depolarization was much slower in the
      transverse direction than in the longitudinal direction. In the transverse
      direction, action potential duration was longest at the closest observation
      point, i.e., 1 mm from the stimulation, site (188 +/- 14 and 267 +/- 18 ms for
      500- and 1,000-ms pacing cycle lengths, respectively). Action potential duration
      progressively shortened as the recording site was moved farther from the
      stimulation site (P < 0.001). The action potential duration 16 mm from the
      stimulation site was 165 +/- 11 and 247 +/- 12 ms for 500- and 1,000-ms pacing
      cycle lengths, respectively. In contrast, the action potential duration in the
      longitudinal direction did not change as the distance between the recording site
      and stimulation site increased. We conclude that, at physiological temperature
      and pacing cycle lengths, sequence of activation significantly influenced action
      potential duration when the propagation of activation was transverse to
      myocardial fiber orientation. When activation propagated parallel to fiber
      orientation, there was little or no change of action potential duration as
      distance increased.

PMID- 9038929
TI  - Endothelial-borne platelet-activating factor and interleukin-8 rapidly immobilize
      rolling neutrophils.
AB  - The kinetics of the response of integrins to activating signal(s) must be rapid
      to ensure that rolling neutrophils are localized at the sites of inflammation.
      From video records, we analyzed the adhesion of individual neutrophils in a flow
      based in vitro model of endothelial hypoxia and reoxygenation. There were
      numerous rolling interactions between flowing neutrophils and P-selectin on human
      umbilical vein endothelial cells after hypoxia, but 90% lasted for < 1 s, with
      approximately 30% converted to stationary attachment via beta 2-integrin(s).
      Interleukin-8 (IL-8) and platelet-activating factor (PAF) were responsible for
      neutrophil activation in this model [G. E Rainger, A. Fisher, C. Shearman, and G.
      B. Nash. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H1398-H1406, 1995]. In
      the presence of a PAF-receptor antagonist, IL-8 acting alone induced conversion
      of rolling to stationary adhesion in as little as 80 ms after the initial
      attachment of a neutrophil, with a median response time of 240 ms. In the
      presence of a monoclonal antibody that neutralized IL-8 activity, PAF acting
      alone required a minimum duration of rolling of 560 ms to promote stationary
      adhesion, with a significantly longer median duration of 720 ms. In a
      reconstituted model, treatment of endothelial cells with hydrogen peroxide
      induced short-lived rolling of neutrophils supported by P-selectin. Exogenously
      added IL-8 and/or PAF bound to the endothelial surface and successfully induced
      the immobilization of neutrophils. Rapid and distinct kinetics of the conversion
      to stationary adhesion were observed again for IL-8 or PAF. Thus although
      endothelial-presented signals differed in their rate of action, neutrophils could
      be localized within one or two endothelial cell diameters of their initial
      adhesive contact point.

PMID- 9038930
TI  - Lack of peripheral modulation of cardiovascular central oscillatory autonomic
      activity during apnea in humans.
AB  - Respiratory sinus arrhythmia (RSA) high-frequency oscillations (HF) and slow
      fluctuations in heart rate (LF) are thought to result from entrainment of a
      medullary oscillator, from the baroreflex, or from a combination of both central
      and baroreflex mechanisms. We sought to distinguish between the alternatives by
      examining with spectral analysis the behavior of heart rate (R-R interval) and
      blood pressure in 10 healthy subjects (mean age 27 +/- 1 yr) during apnea,
      altering the rate of preapnea entrainment stimuli by changing the frequency
      either of respiration (controlled at 0.1 or 0.25 Hz) or of baroreceptor
      stimulation by sinusoidal neck suction (0 to -30 mmHg, 0.1 or 0.2 Hz). During
      apnea the RSA-EF power decreased (from 6.73 +/- 0.15 to 3.67 +/- 0.10 In ms2: P <
      0.0001), regardless of preapnea conditions, whereas LF power was reduced only if
      preceded by 0.1-Hz respiration or neck suction [from 8.71 +/- 0.18 to 6.52 +/-
      0.11 In ms2 (P < 0.001) and from 8.31 +/- 0.23 to 6.90 +/- 0.38 In ms2 (P <
      0.01), respectively]. The LF frequency seen in the R-R interval during apnea was
      slower than the spontaneous LF during 0.25-Hz breathing (0.082 +/- 0.01 vs. 0.112
      +/- 0.001 Hz, P < 0.001), but the maneuvers during preapnea had no influence on
      the observed frequency or other characteristics of the slow oscillations during
      apnea. Moreover, we found no evidence of a progressive decrease in the power of
      the oscillation during apnea. The same behavior was observed on the mean blood
      pressure signal. In conclusion, a slow rhythm is present during apnea. In healthy
      subjects at rest the characteristics of this oscillation indicate that it could
      be generated by a central oscillator this may thus contribute to the origin of LF
      present during normal respiration, in addition to the baroreflex.

PMID- 9038932
TI  - Left ventricular performance assessed by echocardiographic automated border
      detection and arterial pressure.
AB  - Automated echocardiographic measures of left ventricular (LV) cavity area are
      closely correlated with changes in volume and can be coupled with LV pressure
      (PLV) to construct pressure-area loops in real time. The objective was to rapidly
      estimate LV contractility from end-systolic relationships of cavity area (as a
      surrogate for LV volume) and central arterial pressure (Pa) (as a surrogate for
      PLV) in a canine model using automated algorithms. In eight anesthetized mongrel
      dogs, we simultaneously measured PLV, LV area, and Pa (fluid-filled catheter).
      End-systolic pressure-area relationships in terms of pressure-area elastance
      (E'es)] from pressure-area loops during inferior vena caval occlusions were
      determined during basal conditions (control), dobutamine infusion (5-10
      micrograms.mg-1.min-1), and after bolus propranolol (2 mg/kg) with both PLV and
      Pa by semiautomated and automated iterative regression methods. E'es increased
      during dobutamine infusion and decreased after propranolol infusion in all
      animals and with all iterative methods. Estimates of Ees from Pa were closely
      correlated with E'es from PLV by both the semiautomated and automated methods (r
      = 0.93; P < 0.01). The relationship between E'es obtained from Pn for the two
      methods was also closely correlated. Although the automated methods displayed
      larger differences from the semiautomated iterative technique by Bland-Altman
      analysis, the change in E'es with all techniques during dobutamine infusion and
      after propranolol infusion was of similar magnitude and direction among the three
      techniques. Greater variability with the dobutamine runs was partially due to
      abnormally conducted ventricular beats that minimized the number of consecutive
      beats that could be used for these analyses. We conclude that on-line Pa
      recordings from fluid-filled catheters can be used with echocardiographic
      automated border detection to rapidly calculate E'es as a means to estimate LV
      contractility.

PMID- 9038931
TI  - Endothelin ETA receptor regulates signaling and ANF gene expression via multiple
      G protein-linked pathways.
AB  - We have characterized the interaction of endothelin (ET) with cultured neonatal
      rat ventricular myocytes. Binding studies indicate a single population of ETA
      receptors [53,000 sites/cell, apparent dissociation constant (Kd) for ET-1
      approximately 0.07 nM]. Analysis of mRNA levels for ET receptors using 35 cycles
      of reverse transcriptase-polymerase chain reaction demonstrates the presence of
      only ETA-receptor message. Studies with ET-1 and a variety of congeners and
      antagonists indicate that ETA receptors couple to both the stimulation of
      phosphoinositide turnover and the inhibition of adenylyl cyclase. In myocytes
      transfected with an atrial natriuretic factor (ANF) promoter linked to a
      luciferase reporter gene, ET-1 stimulates luciferase expression through an ETA
      receptor. These data indicate that the ETA receptor is the exclusive receptor on
      neonatal ventricular myocytes and that this receptor couples to both
      phosphoinositide hydrolysis and adenylyl cyclase. ET-1 also induces a threefold
      increase in mitogen-activated protein kinase (MAPK) activity, an effect that is
      not sensitive to pertussis toxin (PTx). By contrast, ET-stimulated ANF-luciferase
      expression is partially inhibited by treatment of cells with PTx, suggesting that
      both PTx-sensitive (Gi) and PTx-insensitive (Gq) pathways mediate the effects of
      ET-1 on ANF gene expression in neonatal myocytes and that hormonal regulation of
      ANF expression may utilize pathways in addition to the activation of MAPK.

PMID- 9038933
TI  - Diabetes rapidly induces contractile dysfunctions in isolated ventricular
      myocytes.
AB  - To determine whether diabetes-induced cardiac dysfunction is due to contractile
      dysfunction at the single-cell level, mechanical properties and Ca2+ transients
      were evaluated in ventricular myocytes isolated from diabetic rats. Rats were
      made diabetic by injection with streptozotocin and killed either 4-6 days or 8 wk
      after treatment. Shortening and relengthening (twitch) properties were evaluated
      in isolated myocytes with a high-resolution (120-Hz) video-based edge-detection
      system during electrical stimulation between 0.1 and 5 Hz. A separate cohort of
      myocytes was loaded with fura 2 to assess intracellular Ga2+ transients. Long
      term (8-wk) but not short-term (4- to 6-day) diabetes depressed peak twitch
      amplitude. Diabetes markedly prolonged both the contraction and relaxation phases
      from both diabetic models. Additionally, 35% of the long-term diabetic myocytes
      could not pace at 5 Hz, and 48% of the short-term diabetic myocytes developed a
      hypercontracture at that frequency. Intracellular Ca2+ measurements showed slower
      Ca(2+)-transient decays in myocytes from short-term diabetic rats. These data
      demonstrate that contractile dysfunction seen in the diabetic heart is due, in
      part, to abnormalities of the myocyte. Furthermore, these abnormalities are
      present after only 4-6 days of diabetes, suggesting a rapid alteration in the
      processes regulating myocyte shortening and relengthening, which likely include
      impaired Ca2+ sequestration or extrusion.

PMID- 9038934
TI  - Low insulin and high glucose induce abnormal relaxation in cultured adult rat
      ventricular myocytes.
AB  - One of the most prominent myocardial defects associated with diabetes is abnormal
      diastole. We have recently reported that this dysfunction involves prolonged
      relaxation (relengthening) in isolated ventricular myocytes that occurs within
      days after the induction of diabetes. The present study was designed to evaluate
      the role of insulin and glucose int he etiology of this dysfunction with a serum
      free myocyte culture system. Adult rat ventricular myocytes were cultured for 1-4
      days in a "diabetic-like" medium containing five times less insulin and
      approximately five times more glucose than in our normal medium. Mechanical
      properties and Ca2+ transients (fura 2) were evaluated with a high-resolution
      (120-Hz) video-based edge-detection/spectro-fluormetric system. The cells were
      field stimulated to contract at slow and physiologically relevant rates, and
      indexes of contraction and relaxation were evaluated. Relengthening was markedly
      longer in myocytes cultured in low-insulin-high-glucose (LIHG) medium compared
      with those in normal medium, whereas contraction was unaffected. Intracellular
      Ca2+ transients showed slower rates of decay in myocytes cultured in LIHG medium.
      These data demonstrate that maintaining normal ventricular myocytes in an LIHG
      environment prolongs relaxation in a manner similar to the effects of in vivo
      diabetes. Furthermore, the abnormal relaxation is inducible in 1 day, suggesting
      rapid alterations in processes regulating relaxation, which likely include
      impaired Ca2+ sequestration and/or extrusion.

PMID- 9038935
TI  - Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure
      overload cardiac hypertrophy.
AB  - The alterations of intracellular calcium (Ca2+) homeostasis may be responsible
      for the contractile defects in pressure-overload cardiac hypertrophy. The Ca(2+)
      adenosinetriphosphatase (ATPase) protein level of the sarcoplasmic reticulum (SR)
      is reduced in the hypertrophied or failing heart. However, it is not known
      whether Ca(2+)-storing proteins, including calsequestrin and calreticulin, are
      also altered during cardiac hypertrophy. We quantified SR Ca(2+)-regulatory
      proteins using Western blot analysis in left ventricular (LV) muscle isolated
      from sham-operated control rats (n = 6) and rats with pressure overload 4 wk
      after abdominal aortic constriction (n = 7). The contractile function of isolated
      LV myocytes, assessed by the sarcomere motion measured with laser diffraction,
      was depressed in aortic-constricted rats. The SR Ca(2+)-ATPase protein level was
      decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P <
      0.01). The calsequestrin protein level was not altered, whereas calreticulin was
      increased by 120 +/- 3% of the control value in aortic-constricted rats (P <
      0.05). The alterations in SR Ca(2+)-regulatory proteins were equally observed in
      hypertrophied hearts even when the results were normalized using the amounts of
      myosin heavy chain proteins in each sample. Immunohistochemical staining of
      calsequestrin in the control heart showed cross striations at the Z lines,
      whereas calreticulin was hardly observed within myocytes but was intense within
      interstitial fibroblasts. In the hypertrophied heart, calreticulin was observed
      at the perinuclear region within the myocyte cytoplasm. These data indicate that
      pressure-overload cardiac hypertrophy causes the alterations in SR Ca(2+)-storing
      proteins as well as in Ca(2+)-ATPase, which may contribute to the contractile
      dysfunction of the hypertrophied myocytes.

PMID- 9038936
TI  - Effect of nitric oxide synthase inhibitors on endothelial [Ca2+]i and microvessel
      permeability.
AB  - To investigate the mechanism whereby nitric oxide (NO) signaling pathways
      regulate microvessel permeability in vivo, we measured changes in microvessel
      hydraulic conductivity (Lp) and endothelial cytoplasmic calcium concentration
      ([Ca2+]i) in response to calcium ionophore, ionomycin (5 microM), and ATP (10
      microM) before and after the use of NO synthase (NOS) inhibitors in single
      perfused frog mesenteric venular microvessels. Ionomycin induced a transient
      increase in endothelial [Ca2+]i and an associated increase in Lp. The NOS
      inhibitors N omega-nitro-L-arginine methyl ester (10 and 300 microM) and N omega
      monomethyl-L-arginine (L-NMMA; 10, 50, and 100 microM) significantly attenuated
      the peak increase in Lp induced by ionomycin. A similar inhibitory effect was
      also observed with the increase in Lp mediated by ATP. In contrast, D-NMMA, a
      biologically inactive isomer of L-NMMA, showed no effect on ionomycin-induced
      increase in Lp L-Arginine (3 mM) reversed the inhibitory effect of L-NMMA (10
      microM) on Lp. However, the NOS inhibitors did not alter the magnitude and time
      course of the biphasic increase in endothelial [Ca2+]i induced by both ionomycin
      and ATP. These data suggest that 1) calcium-dependent NO release is a necessary
      step to increase microvessel permeability, and 2) the action of NOS inhibitors in
      attenuating the permeability increase in response to ionomycin and ATP occurs
      down-stream from calcium entry and does not involve modification of the initial
      increase in endothelial [Ca2+]i.

PMID- 9038937
TI  - Characterizing ventricular mechanics and energetics following repeated coronary
      microembolization.
AB  - Myocardial mechanics and energetics were investigated in an animal model of
      moderate chronic heart failure (CHF) created by repeated coronary
      microembolizations in six dogs. The final fractional area change was 34 +/- 4%.
      Hearts of these animals were isolated and cross-perfused, and balloons were
      placed in the left ventricle (LV). Chamber contractile state was markedly
      depressed in embolized hearts as assessed by the slope (Ees 2.74 +/- 0.49 vs.
      4.00 +/- 1.18 mmHg/ml, P < 0.01) and volume axis intercept (V: 8.7 +/- 5.9 vs.
      1.0 +/- 3.2 ml, P < 0.01) of end-systolic pressure-volume relation compared with
      a group of six normal dogs. The end-diastolic pressure-volume relation of
      embolized hearts was shifted to the right, indicating a dilation of the LV.
      However, systolic and diastolic stress strain relationships were similar in the
      two groups, suggesting that the average myocardial properties of the embolized
      hearts are similar to those of normal hearts. The relationship between oxygen
      consumption and pressure-volume area in embolized hearts had smaller intercept
      (2.98 +/- 0.44 vs 3.92 +/- 0.39 x 10(-2) ml O2.beat-1.100 g LV-1, P < 0.01)
      compared with the control group, with no change in the slope. These results
      contrast with previous findings in pacing CHF and serve as an important
      characterization of ventricular properties in this model of CHF from different
      etiology.

PMID- 9038938
TI  - ATP-dependent regulation of a G protein-coupled K+ channel (GIRK1/GIRK4)
      expressed in oocytes.
AB  - Recent studies suggest that activation of the atrial muscarinic K+ current by
      acetylcholine (ACh) involves an ATP-dependent process that is then inhibited by a
      cytosolic protein to result in the rapid desensitization. To obtain further
      evidence in support of such a dually regulated process, we studied the properties
      of GIRK1 and GIRK4, which, when coexpressed in oocytes, form a heteromultimer
      that closely resembles the muscarinic K+ channel. ACh activated an inwardly
      rectifying K+ current that desensitized slowly. In cell-attached patches with ACh
      in the pipette, the mean open times (tau zero) of GIRK1/GIRK4 were 1.2 +/- 0.1
      (28%) and 6.7 +/- 0.8 ms (72%) and did not change significantly with time.
      However, in inside-out patches, the tau zero of GIRK1/GIRK4 activated with
      guanosine 5'-O-(3-thiotriphosphate) was 1.3 +/- 0.1 ms (100%), and the channel
      activity (NP0) was almost fivefold lower. These changes in channel kinetics did
      not occur in the presence of sodium orthovanadate (3 mM), an inhibitor of
      phosphatase. Addition of 1 mM ATP, but not adenylimidodiphosphate, to inside-out
      patches resulted in increases in NP zero (4.8-fold) and the open-time duration of
      GIRK1/GIRK4, such that tau zero were 1.2 +/- 0.2 (32%) and 6.2 +/- 0.6 ms (68%).
      Single channel conductances were unchanged (34 +/- 1 pS). Cytosolic extract from
      atria, but not oocytes, could reverse these effects of ATP. These results provide
      further evidence that the antagonistic modulation of G protein-gated K+ channels
      by ATP and the atrial cytosolic protein produces the early rapid desensitization
      in atrial cells. In oocytes the ATP-dependent step is dominant and thus provides
      a major component of the total GIRK1/GIRK4 current activated by ACh.

PMID- 9038939
TI  - Nitric oxide-dependent and -independent norepinephrine release in rat mesenteric
      arteries.
AB  - The role of nitric oxide (NO) in endogenous norepinephrine (NE) release in the
      perfused isolated rat mesenteric vasculature was examined. NE overflow elicited
      by electrical field stimulation (EFS) at various frequencies was significantly
      smaller at 24 than at 37 degrees C. The pressor response upon EFS at 8 and 10 Hz,
      however, was higher at 24 than at 37 degrees C. When production of NO was blocked
      by N omega-nitro-L-arginine (L-NNA), NE overflow upon EFS at each frequency of
      stimulation was diminished by 50% at 37 degrees C but remained unchanged at 24
      degrees C, whereas the pressor response elicited by EFS became greater at 37 than
      at 24 degrees C. These effects of L-NNA were reversed by L-arginine, but not by
      its D-enantiomer. Sodium nitroprusside, an NO donor, increased EFS-elicited NE
      overflow at 24 degrees C but had no effect at 37 degrees C. These results
      demonstrate that NE release is NO dependent and NO independent. The NO-dependent
      mechanism is more sensitive to cooling than the NO-independent mechanism. The
      increase in EFS-elicited perfusion pressure at 24 degrees C may be due to
      reduction in synthesis of NO (a potent vasodilator), thus unmasking the effect of
      NE and other noncatecholamine vasoconstrictors.

PMID- 9038940
TI  - Captopril suppresses interstitial fibrin deposition in coxsackievirus B3
      myocarditis.
AB  - The effects of captopril on murine coxsackievirus B3 (CB3) myocarditis were
      investigated, with focus on interstitial fibrin deposition and changes in the
      connective tissue matrix. Captopril was administered intraperitoneally at a dose
      of 0.1 mg/g to CB3-infected mice daily on days 10-30 in experiment I
      (inflammatory phase) and on days 30-60 in experiment II (fibrotic phase). In
      experiment I, mouse survival was higher in the captopril-treated group than in
      the untreated group. Histological improvement, including prevention of
      extravasated fibrin deposition, maintenance of connective tissue architecture,
      suppression of myocyte hypertrophy, and prevention of myosin isoform shift from
      alpha to beta, was observed in captopril-treated mice in experiment I, but not in
      experiment II; in experiment II, captopril administration suppressed thickening
      of the interstitial reticulin fibers. Captopril inhibited inflammatory fibrin
      deposition, postmyocarditic myocyte hypertrophy, and ventricular remodeling
      during the inflammatory phase, but not during the fibrotic phase, of CB3
      myocarditis in mice.

PMID- 9038941
TI  - Assessment of cardiomyocyte DNA synthesis in normal and injured adult mouse
      hearts.
AB  - Cardiomyocyte DNA synthesis was examined in normal and injured adult mouse
      hearts. In preliminary studied DNA synthesis was monitored by [3H]thymidine
      incorporation, followed by autoradiographic analysis of dispersed cell
      preparations. No synthetic cells were identified when 20,000 ventricular
      cardiomyocytes from normal adult hearts were examined. A high throughput assay
      was developed to establish the actual labeling index for the adult mouse heart.
      The assay utilized [3H]thymidine incorporation in transgenic mice which expressed
      a nuclear-localized beta-galactosidase (beta-Gal) reporter gene exclusively in
      cardiac myocytes. Cardiomyocyte DNA synthesis was evidenced by colocalization of
      beta-Gal activity and silver grains in autoradiograms of histological sections.
      Examination of 180,000 ventricular cardiomyocyte nuclei from normal adult
      transgenic mice identified a single synthetic nucleus, suggesting a maximum
      labeling index of 0.0005%. Cardiomyocyte DNA synthesis was next examined in
      hearts injured by focal cauterization of the left ventricular free wall. Only
      three synthetic nuclei were identified when 36,000 cardiomyocyte nuclei in the
      perinecrotic zone of the injured heart were examined. No additional synthetic
      nuclei were identified when 180,000 nuclei in regions distal to the necrotic zone
      were examined. These data confirm that cardiomyocyte DNA synthesis in the adult
      mouse heart is extremely rare and provide baseline data for analyses in
      genetically modified animals.

PMID- 9038942
TI  - Properties of human atrial ICa at physiological temperatures and relevance to
      action potential.
AB  - There are no published characterizations of Ca2+ current (ICa) at physiological
      temperatures in human atrium. Depolarization of human atrial myocytes at 36
      degrees C elicited ICa that peaked at +10 mV, with a mean maximum current density
      of 10.8 +/- 1.1 pA/pF and no evidence for T-type current. Overlap between
      activation and inactivation curves and incomplete inactivation during pulses
      comparable to normal action potential duration (APD) were compatible with the
      observed role of ICa in maintaining the plateau. ICa was frequency dependent
      between 0.1 and 2 Hz and ICa blockade with 0.2 mM Cd2+ reduced rate-dependent
      changes in APD: under control, APD at 90% repolarization was 230 +/- 15 ms at 0.1
      Hz and 178 +/- 14 ms at 2 Hz (decrease of 52 +/- 5 ms); with Cd2+, values were
      121 +/- 7 ms at 0.1 H2 and 115 +/- 6 ms at 2 Hz (decrease of 6 +/- 3 ms, P <
      0.01) Isoproterenol (1 microM) increased ICa and prolonged APD from 138 +/- 13 to
      199 +/- 15 ms (P < 0.01). These results indicate that, in human atrial cells at
      36 degrees C, the properties of L-type ICa contribute importantly to the rate
      dependent and autonomic control of APD.

PMID- 9038943
TI  - In situ visualization of spontaneous calcium waves within perfused whole rat
      heart by confocal imaging.
AB  - We describe the first direct visualization of Ca2+ oscillations in the perfused
      whole rat heart. Dye loading at a low temperature and enhanced optical-section
      techniques of confocal microscopy by elimination of the refractive index mismatch
      with use of saline-immersible objective lens enabled us to image multiple Ca2+
      waves in the subepicardial myocardium of the fluo 3-loaded heart. These Ca2+
      waves were sporadically seen even with a physiological extracellular Ca2+
      perfusion in either a paced or an arrested heart and propagated beyond cellular
      boundaries within the three-dimensional structures of cardiac muscle. Under these
      conditions, the velocity of wave propagation was 60-100 microns/s and the
      frequency of initiation was relatively low (< 2 Hz). With an increase in
      extracellular Ca2+ concentration, however, the waves became more prevalent and
      tended to be multifocal, and an increasing fraction of the waves exhibited faster
      propagation velocities and higher frequencies. These results suggest that
      perfused rat hearts exhibit spontaneous Ca2+ waves in an apparently resting state
      and that under Ca(2+)-overload conditions the multifocal and high-frequency waves
      become more widespread in the heart syncytium, which may provide an understanding
      of the ionic basis for the summation of afterdepolarizations and triggering of
      arrhythmias seen under pathological conditions.

PMID- 9038944
TI  - Redistribution of intracellular Ca2+ stores after beta-adrenergic stimulation of
      rat tail artery SMC.
AB  - beta-Adrenergic agonists induce the relaxation of vascular smooth muscle by a
      mechanism that activates the extrusion of Na+ and Ca2+ from the cell. A primary
      source of contractile Ca2+ resides in the sarcoplasmic reticulum (SR), which
      releases Ca2+ in response to vasoactive agents through inositol trisphosphate
      mediated channels. To determine if smooth muscle relaxation induced by beta 2
      adrenergic agonists involves the redistribution of intracellular Ca2+, we studied
      the effects of isoproterenol (Iso) on freshly isolated, single rat tail artery
      smooth muscle cells loaded with fura 2, using digital ratiometric fluorescence
      imaging. Stimulation with 1 microM phenylephrine (PE) or norepinephrine produced
      phasic and tonic increases in cytoplasmic intracellular Ca2+ concentration
      ([Ca2+]i) associated associated with cell shortening. Exposure to caffeine and to
      Ca2(+)-free solutions eliminated the phasic and tonic components, respectively,
      from the Ca2+ signal. Intermittent superfusion with PE or caffeine was used to
      evaluate SR Ca2+ stores after stimulation by Iso. Exposure to 1 microM Iso
      induced a time-dependent decrease in PE-activated peak and tonic [Ca2+]i without
      any change in resting [Ca2+]i. Intermittent stimulation with 10 mM caffeine
      revealed a similar decline in peak [Ca2+]i, indicating Iso-dependent depletion of
      SR Ca2+ stores. The Ca2+ that remained in the SR after prolonged exposure to Iso
      (30% of the pre-Iso level by 80 min at 22 degrees C) failed to elicit a
      contractile response. The cells, perfused with a Na(+)- and Ca2(+)-free medium to
      block Na+/ Ca2+ exchange, prevented depletion of the SR Ca2+ stores by Iso. We
      propose that Iso inhibits agonist-mediated Ca2+ influx through sarcolemmal Ca2+
      channels and activates Ca2+ redistribution from storage sites in the SR to the
      extracellular compartment by a mechanism that involves Na+/Ca2+ exchange. These
      combined effects of Iso facilitate smooth muscle relaxation (and reduce vascular
      tonus) by reducing the increase in cytoplasmic Ca2+ evoked by vasoconstrictors.

PMID- 9038945
TI  - Effect of nitric oxide and potassium channel agonists and inhibitors on basilar
      artery diameter.
AB  - The first goal of this study was to examine the hypothesis that dilatation of the
      basilar artery in response to activation of ATP-sensitive K+ channels is mediated
      by nitric oxide (NO). Diameter of the basilar artery (209 +/- 5 microns, mean +/-
      SE) was measured using a cranial window in anesthetized rats. Aprikalim (a direct
      activator of ATP-sensitive K+ channels) dilated the basilar artery under control
      conditions. Inhibition of endogenous NO production with NG-nitro-L-arginine (L
      NNA, 10(-4) M) did not alter responses to aprikalim. The second goal was to
      determine whether vasodilatation in response to NO is dependent on activation of
      calcium-activated K+ channels. Tetraethylammonium (TEA, 10(-3) M), an inhibitor
      of calcium-activated K+ channels, did not affect dilator responses to sodium
      nitroprusside (an NO donor) under control conditions. Responses to nitroprusside
      (10(-8) and 10(-7) M) were augmented more than twofold during application of L
      NNA. In the presence of L-NNA, the augmented portion of the response to
      nitroprusside was inhibited by TEA and iberiotoxin (5 x 10(-8) M, a highly
      selective inhibitor of calcium-activated K+ channels), but it was not inhibited
      by glibenclamide (10(-6) M), an inhibitor of ATP-sensitive K+ channels. These
      findings suggest that dilator responses of the basilar artery to an activator of
      ATP-sensitive potassium channels are not mediated by NO. Calcium-activated K+
      channels may not normally contribute to dilator responses of the basilar artery
      to nitroprusside. The effects of TEA and iberiotoxin suggest that when endogenous
      production of NO is inhibited, sodium nitroprusside causes the opening of calcium
      activated K+ channels, contributing to an augmented vasodilator response.

PMID- 9038946
TI  - NO modulates autonomic effects on sinus discharge rate and AV nodal conduction in
      open-chest dogs.
AB  - The purpose of this study was to investigate the role of nitric oxide (NO) in
      mediating vagal and sympathetic modulation of spontaneous sinus cycle length
      (SCL) and atrioventricular (AV) nodal conduction time (A-H interval) in 62 open
      chest mongrel dogs anesthetized with alpha-chloralose. Infusion of an NO synthase
      (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 4 mg/ ml), into the sinus and
      AV nodal arteries attenuated significantly (P < 0.01) the negative chronotropic
      and dromotropic responses to vagal nerve stimulation (VS) and VS during ansae
      subclaviae stimulation (SS) or isoproterenol (Iso) infusion. Intravenous
      administration of L-arginine (100 mg/kg) reversed these responses toward control
      values, whereas D-arginine did not have a significant effect. L-NMMA
      significantly (P < 0.01) enhanced the effects of SS and Iso on SCL and A-H
      interval; L-arginine reversed these changes toward baseline. L-NMMA increased the
      minimum concentration of ACh needed to induce 50 or 100% prolongation of SCL or
      second-degree or complete AV block during concomitant Iso infusion. L-Arginine
      reversed these effects. NOS inhibition did not affect the direct cholinergic
      actions of ACh on SCL and A-H interval but enhanced adrenergic positive
      chronotropic and dromotropic effects. We conclude that NO plays a stimulatory
      role in mediating vagal neurotransmission and vagal modulation of sympathetic
      effects and an inhibitory role in mediating sympathetic neurotransmission.

PMID- 9038947
TI  - Role of KATP channels on modulating diaphragmatic microvascular flow during
      hemorrhagic hypotension.
AB  - The effects of glibenclamide (GLB), a specific blocker of ATP-sensitive potassium
      (KATP) channels, and tetraethylammonium (TEA) on modulating the regulation of
      diaphragmatic microcirculation were assessed in anesthetized mechanically
      ventilated rats. With bicarbonate-buffered Ringer solution continuously suffusing
      the left hemidiaphragm, microcirculatory blood flow was recorded by laser-Doppler
      flowmetry (QLDF). Hemorrhagic hypotension (HH) was induced via bleeding into a
      pressure reservoir. Five sets of experiments were performed. In set 1 (n = 6),
      the vasodilator effect of diazoxide (3 x 10(-4) M) was abolished after a 30-min
      suffusion with GLB, whereas the vasodilator effect of sodium nitroprusside (3 x
      10(-6) M) remained the same. In set 2 (vehicle + HH; n = 23), a stepwise
      reduction in systemic arterial blood pressure (ABP) induced two distinct patterns
      of microvascular responses. Regulation of QLDF could be observed in pattern A
      animals in a range of ABP from 113 to 52 mmHg, whereas QLDF in pattern B animals
      rose progressively with declining ABP. In set 3 (GLB + HH; n = 17), baseline
      values of QLDF were not significantly affected after a 30-min suffusion of GLB
      (10(-5) M). During HH, two microvascular patterns similar to those in set 2 were
      observed. GLB significantly potentiated the reduction in QLDF in pattern A
      animals. In contrast, GLB had no effect on QLDF in pattern B animals. In set 4
      (TEA + HH; n = 17), similar microvascular responses, compared with the vehicle
      group, were observed during HH after a 30-min suffusion of TEA (2 x 10(-3) M). In
      set 5 (n = 5), baseline values of QLDF were not significantly altered during sham
      hypotension. We conclude that 1) KATP channels are functional but not active in
      the resting diaphragmatic microcirculation and 2) KATP channels can modulate
      regulation of the microcirculation in the resting diaphragm during HH.

PMID- 9038948
TI  - Neutrophil recruitment as a factor limiting injury or promoting recovery from
      acute lung injury.
AB  - We studied 1) neutrophil mobilization in sheep given endotoxin (10 ng.kg-1.min-1,
      n = 5) for 4 h, 2) surviving (n = 17) and nonsurviving sheep (n = 8) during a 12
      h infusion of endotoxin, and 3) adult sheep (n = 8) or lambs (n = 8) infused with
      endotoxin for 12 h. Bone marrow cells of sheep declined from a baseline value of
      10,533 +/- 1,784 to 5,966 +/- 1,980 cells/microliter (P < 0.05) 4 h after
      endotoxin. After 12 h of endotoxin infusion, circulating neutrophils remained
      reduced from baseline values of 2,000-4,000 cells/microliter to 343 +/- 70 in
      lambs and 484 +/- 236 in nonsurviving sheep, while beginning to recover in
      surviving sheep to 1,838 +/- 467 cells/microliter. In lambs and nonsurviving
      sheep, a 12-h infusion of endotoxin increased lung lymph protein clearance
      tenfold compared with a fivefold increase in surviving sheep. Neutrophils
      cultured from sheep bone marrow exposed to lamb postendotoxin plasma failed to
      increase in cell number (609 +/- 229 to 610 +/- 182 cells/microliter), whereas
      similar cells exposed to adult sheep postendotoxic plasma showed a significant
      increase in cell number (1,069 +/- 101 to 2,293 +/- 448 cells/microliter, P <
      0.05). Our results are consistent with the hypothesis that the ability to recruit
      neutrophils to the circulation during periods of inflammation is important in
      limiting the severity of acute lung injury.

PMID- 9038949
TI  - Endothelium-dependent pulmonary vasodilation is selectively attenuated during
      isoflurane anesthesia.
AB  - We have recently reported that halothane (Hal) anesthesia attenuates the
      pulmonary vasodilator responses to both bradykinin (BK) and sodium nitroprusside
      (SNP) compared with responses measured in the conscious state. These agonists
      have been classically used to activate endothelium-dependent and -independent
      vasodilator pathways, respectively. Our present goal was to assess the effect of
      isoflurane (Iso) anesthesia on pulmonary vasodilation activated via these
      pathways. Left pulmonary vascular pressure-flow (P-Q) plots were used to measure
      the pulmonary vascular responses to cumulative intravenous doses of BK, SNP, and
      3-morpholinosydonimine-N-ethylcarbamide (SIN-1), a nitric oxide donor, in
      chronically instrumented dogs in the conscious state and during Iso anesthesia
      after matched preconstriction with the thromboxane analogue U-46619. Iso
      attenuated the vasodilator response to BK (P < 0.05). However, Iso had a
      differential effect on the responses to SIN-1 and SNP. Iso potentiated the
      vasodilator response to SIN-1 (P < 0.05), whereas Iso attenuated the response to
      SNP (P < 0.05). The vasodilator response to SIN-1 was unchanged during Hal
      anesthesia. The ATP-sensitive potassium (KATP)-channel inhibitor glibenclamide
      attenuated the vasodilator response to SNP (P < 0.05) but not to SIN-1. Thus Iso
      and Hal selectively attenuate the endothelium-dependent pulmonary vasodilator
      response to BK. Both anesthetics attenuate vasodilation induced by SNP but not by
      SIN-1. Moreover, a component of SNP-induced vasodilation involves KATP-channel
      activation.

PMID- 9038950
TI  - Actions of lidocaine on reentrant ventricular rhythms in the subacute myocardial
      infarction period in dogs.
AB  - The actions of lidocaine were studied in 18 dogs, 4 days after ligation of the
      left anterior descending artery, by computerized mapping. Lidocaine only
      occasionally suppressed the induction of reentry. At fast heart rates, lidocaine
      actually facilitated the induction of reentry. The effects on conduction and
      refractoriness of normal and ischemic myocardium were measured using high
      resolution techniques. Lidocaine promoted reentry by a rate-dependent increase in
      refractory gradient, resulting in additional block, and a selective decrease in
      conduction velocity in ischemic tissue, resulting in additional conduction delay.
      Lidocaine could prevent reentry through a rate-independent differential increase
      in refractory period gradient at the entrance to the common pathway of the
      circuit, causing block of the reentrant impulse. We conclude that the
      proarrhythmic effect of lidocaine is due to increased conduction delay and block
      while the antiarrhythmic effect is due to block of the reentrant impulse by
      prolonged refractoriness in the common pathway.

PMID- 9038951
TI  - Intrapericardial administration of adenovirus for gene transfer.
AB  - Gene transfer to the heart has been accomplished with intravascular
      administration of adenoviral vectors into the pericardial sac, by increasing the
      duration of exposure to the adenovirus, would result in gene expression in the
      pericardium and perhaps myocardium and therefore might provide an alternative
      method to intravascular administration for gene transfer. We injected a
      replication-deficient adenovirus (average 1 x 10(12) particles/ml in 3% sucrose;
      1 x 10(10) plaque forming units/ml containing cDNA encoding a nuclear-targeted
      bacterial beta-galactosidase into the pericardial sac of dogs. Samples of the
      pericardium and heart were examined for enzymatic activity of beta-galactosidase
      and after histochemical staining with 5-bromo-4-chloro-3-indolyl-beta-D
      galactopyranoside. One day after injection of the adenovirus (1-3 ml), beta
      galactosidase activity was highest in the parietal pericardium and left atrial
      tissue and lower in the right and left ventricles. Histochemical expression of
      the transgene was predominantly in the visceral pericardium of atria and
      ventricles and occasionally in the epicardial myocytes, arterioles, and venules.
      Pretreatment with doxycycline (5 mg) before adenovirus administration increased
      transgene activity in left ventricles. Thus adenovirus injected into the
      pericardial sac provides an effective method for gene transfer to the visceral
      and parietal pericardium over atria and ventricles.

PMID- 9038952
TI  - Intracellular lactate controls adenosine output from dog gracilis muscle during
      moderate systemic hypoxia.
AB  - The influence of systemic hypoxia on lactate and adenosine output from isolated
      constant-flow-perfused gracilis muscle was determined in anesthetized dogs. The
      lactate transport inhibitor alpha-cyano-4-hydroxycinnamic acid (CHCA) was
      employed to distinguish the direct effects of hypoxia on adenosine output from
      the effects produced indirectly by a change in lactate concentration. Reduction
      of arterial PO2 from 135 +/- 4 to 39 +/- 2 mmHg raised arterial lactate from 1.26
      +/- 0.32 to 2.22 +/- 0.45 mM but decreased venoarterial lactate difference from
      0.53 +/- 0.09 to -0.13 +/- 0.19 mM, indicating that lactate output from the
      muscle was abolished. Arterial adenosine did not change, but venoarterial
      adenosine difference increased from 20.6 +/- 10.1 to 76.5 +/- 14.4 nM. CHCA
      infusion during hypoxia abolished adenosine output from gracilis muscle
      (venoarterial adenosine difference = -20.5 +/- 40.6 nM). In isolated rat soleus
      muscle fibers, intracellular pH increased from 6.96 +/- 0.04 to 7.71 +/- 0.14 in
      response to a reduction of PO2 from 459 +/- 28 to 53 +/- 3 mmHg. Correspondingly,
      adenosine output decreased from 3.71 +/- 0.15 to 3.04 +/- 0.27 nM. These data
      suggest that hypoxia did not directly stimulate adenosine output from red
      oxidative skeletal muscle, but rather systemic hypoxia increased lactate delivery
      and the resulting increase in intracellular lactate decreased intracellular pH,
      which stimulated adenosine output.

PMID- 9038953
TI  - Modulation of ATP-sensitive K+ channels in rabbit ventricular myocytes by
      adenosine A1 receptor activation.
AB  - The objective of the present study was to characterize the role of adenosine in
      the regulation of ATP-sensitive K (KATP) channel activity in isolated rabbit
      ventricular myocytes using the patch-clamp technique. In an outside-out patch
      exposed to guanosine 5'-triphosphate and ATP at the intracellular surface,
      external adenosine stimulated KATP channel activity. In an inside-out patch
      exposed to external adenosine, ATP reduced KATP channel activity and guanosine 5'
      triphosphate stimulated KATP channel activity. Guanosine 5'-O-(3
      thiotriphosphate) resulted in a gradual increase of KATP channel activity even in
      the absence of adenosine. When myocytes were preincubated with pertussis toxin or
      8-cyclopentyl-1,3-dipropylxanthine, adenosine A1 receptor activation failed to
      activate the KATP channel. Analysis of the open and closed time distributions
      showed that adenosine A1 receptor activation increased burst duration and
      decreased interburst duration. In a dose-response relationship for ATP, adenosine
      A1 receptor activation shifted the half-maximal inhibition of the KATP channel
      from 70 to 241 microM.

PMID- 9038954
TI  - KATP channels and memory of ischemic preconditioning in dogs: synergism between
      adenosine and KATP channels.
AB  - Results from numerous studies have shown that there is an important link between
      adenosine A1 receptors and ATP-sensitive potassium (KATP) channels in mediating
      the cardioprotective effects of ischemic preconditioning (PC). The major aim of
      the present study was to determine whether occupation of A1 receptors and/or the
      opening of KATP channels is involved in the time delay between the PC stimulus
      and the prolonged ischemic insult or the "memory" of PC to reduce infarct size.
      Barbital sodium-anesthetized dogs were subjected to 1 h of left anterior
      descending coronary artery (LAD) occlusion followed by 4 h of reperfusion.
      Ischemic PC was elicited by 10 min of LAD occlusion followed by 1 h of
      reperfusion (1-h memory) before the 1-h occlusion period. Either adenosine (800
      g/min), bimakalim (3 g/min), a combination of two lower doses of each agent (400
      g/min of adenosine and 0.3 g/min of bimakalim), or an equivalent volume of saline
      was infused into the LAD for 10 min followed by a 1-h drug-free period before the
      1-h ischemic insult. In another series, glibenclamide, 8-cyclopentyl-1,3
      dipropylxanthine (a selective A1-receptor blocker), or PD-115199 (a nonselective
      adenosine-receptor antagonist) was administered 50 min after ischemic PC (10 min
      before the 1-h occlusion period). Infarct size (IS) was expressed as a percentage
      of the area at risk. PC with 1 h of reperfusion resulted in a marked reduction in
      IS (8.1 +/- 6.5 vs. 29.8 +/- 5.8% in control dogs). Administration of adenosine
      or bimakalim followed by a 1-h drug-free period had no effect on IS; however, the
      simultaneous administration of adenosine and bimakalim resulted in a marked
      decrease in IS (11.5 +/- 2.7%). One hour after ischemic PC, administration of
      glibenclamide blocked the protective effect of ischemic PC, whereas 8-cyclopentyl
      1,3-dipropylxanthine or PD-115199 did not affect it. These results provide
      evidence that the opening of myocardial KATP channels may play an important role
      in the memory of ischemic PC in the canine heart and also suggest that adenosine
      and the KATP channel may have a synergistic interaction that is important for the
      memory phase of PC.

PMID- 9038956
TI  - Arachidonic acid enhances contraction and intracellular Ca2+ transients in
      individual rat ventricular myocytes.
AB  - Modulation of intracellular free Ca2+ concentration ([Ca2+]i) by inotropic
      stimuli alters contractility in cardiac muscle. Arachidonic acid (AA), a
      precursor for eicosanoid formation, is released in response to receptor
      activation and myocardial ischemia and has been demonstrated to alter K+ and Ca2+
      channel activity. We investigated the effects of AA on contractility by
      simultaneously measuring [Ca2+]i and shortening in single field-stimulated rat
      ventricular myocytes. [Ca2+]i transients were measured using fura 2, and myocyte
      shortening was assessed using video edge detection. AA stimulated a doubling in
      the amplitude of the [Ca2+]i transient and a twofold increase in myocyte
      shortening. In addition, AA stimulated a 30% increase in the time to 50%
      diastolic [Ca2+]i and a 35% increase in the time to 50% relengthening. These
      effects of AA were mediated by AA itself (56 +/- 5%) and by cyclooxygenase
      metabolites. Pretreatment with the protein kinase C inhibitors staurosporine and
      chelerythrine nearly abolished (> 90% inhibition) these AA-induced effects.
      Inhibition of voltagegated K+ channels with 4-aminopyridine mimicked the effects
      of AA. Addition of AA to the 4-aminopyridine-treated myocyte had no additional
      effect on parameters of contractile function. These data indicate that AA alters
      the amplitude and duration of Ca2- transients and myocyte shortening via protein
      kinase C-dependent inhibition of voltage-gated K+ channels. Release of AA by
      phospholipases in response to receptor activation by endogenous mediators or
      pathological stimuli may be involved in mediating inotropic responses in cardiac
      muscle.

PMID- 9038955
TI  - Regional glucose uptake within hypoperfused swine myocardium as measured by
      positron emission tomography.
AB  - Chronic myocardial ischemia and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake were
      studied with positron emission tomography in 12 swine instrumented with an
      external constrictor on the left anterior descending coronary artery (LAD).
      Serial changes in function (by echocardiography), blood flow (with H215O) and FDG
      were determined weekly. At 1 wk, function was normal and FDG uptake in the LAD
      and non-LAD regions was 0.43 +/- 0.12 and 0.45 +/- 0.11 mumol. min-1.g-1,
      respectively (not significant). At approximately 5 wk, LAD wall thickening
      decreased to 18 +/- 5 from 27 +/- 8% (P < 0.05), whereas LAD and non-LAD blood
      flows were 0.68 +/- 0.28 and 1.03 +/- 0.25 ml.min-1.g-1, respectively (P < 0.05).
      At that time, FDG uptake in LAD and non-LAD regions was 0.60 +/- 0.43 and 0.49 +/
      0.30 mumol.min-1.g-1, respectively (P < 0.05). By the use of transmural biopsies
      (n = 6), ATP and creatine phosphate in the LAD region were 3.62 +/- 0.73 and 5.91
      +/- 1.44 mumol/g wet wt, respectively, and neither differed from values in remote
      regions. In this model of chronic ischemia, hypoperfused dysfunctional regions
      were characterized by enhanced glucose uptake and preserved bioenergetics. This
      supports the concept that the myocardium adapts to chronic ischemia.

PMID- 9038957
TI  - Myocardial infarction alters myofilament calcium sensitivity and mechanical
      behavior of myocytes.
AB  - To determine whether myocardial infarction leads to alterations in myofilament
      isometric tension as a function of Ca2+ concentration, unloaded shortening
      velocity, and sarcomere compliance, these properties were examined in skinned
      myocytes 7 days after coronary artery occlusion. Changes in myofilament proteins
      were also evaluated Myocardial infarction was characterized by a 10-15% reduction
      in myofilament isometric tension at submaximum Ca2+ levels in the physiological
      range. However, developed tension at maximum activation was unaltered.
      Conversely, unloaded shortening velocity was decreased by 31% in the remaining
      viable cells, whereas resting tension was increased by 30-40%. The regulatory
      protein troponin I content was reduced, but phosphorylation of troponin I and
      troponin T was increased. Myosin isoenzymes and troponin T contents were not
      altered. In conclusion, molecular responses occurred acutely after myocardial
      infarction, and these adaptations may depress the mechanical behavior of the
      unaffected cells, contributing to acute impairment in global cardiac pump
      function beyond that resulting from myocyte loss.

PMID- 9038958
TI  - Dissociation between adenosine release, MVO2, and energy status in working guinea
      pig hearts.
AB  - Rapid adaptation of ATP formation and coronary flow is required when cardiac work
      is altered. Cardiac energy status was proposed to control both oxygen consumption
      (MVO2) and release of vasoactive adenosine (AR). To investigate the hypothesis of
      a linear relation between free AMP and AR, we employed 31P nuclear magnetic
      resonance (NMR) in a newly elaborated guinea pig heart performing pressure-volume
      work. Under basal conditions, MVO2 was 7.8 +/- 1.0 mumol.min-1.g-1, free AMP 297
      +/- 189 nM and AR 226 +/- 179 pmol.min-1.g-1 (n = 29). Decreasing arterial PO2 by
      50% reduced MVO2 and increased free AMP by 29%; however, AR rose threefold (n =
      5). Doubling oxygen content of the perfusion medium (fluorocarbon emulsion) did
      not alter MVO2, free AMP, or AR (n = 6). When afterload was doubled, MVO2
      increased (+45%) and AR decreased (-60%) despite no change in ADP or AMP (n = 6).
      Dobutamine increased MVO2 (+50%) and AMP (-98%); however, AR rose more than five
      times (n = 8). Switching substrates from glucose + pyruvate to glucose diminished
      MVO2 and increased ADP twofold and AMP fourfold, whereas AR remained constant (n
      = 6). Our findings demonstrate that cardiac energy status is also not the prime
      regulator of oxidative phosphorylation in the isolated heart. Changes in the
      oxygen supply-to-demand ratio induced a rise in AR that exceeded by far the
      increase in free AMP. Thus, additional factors, possibly inhibition of adenosine
      kinase, influence the release of vasoactive adenosine.

PMID- 9038959
TI  - Pulmonary microvascular reflection coefficients estimated with modified lymphatic
      washdown technique.
AB  - Many investigators have used the lymphatic protein washdown technique to estimate
      the pulmonary microvascular membrane reflection coefficient to protein (sigma d).
      With that technique, the investigator causes a high microvascular filtration rate
      then estimates sigma d from the lymph and plasma protein concentrations. However
      the lymph may contain protein washed from the lung tissue, and the tissue protein
      may cause investigators to underestimate sigma d. Plasma protein osmotic pressure
      (IIc) may cause investigators to underestimate sigma d because IIc opposes fluid
      filtration. To minimize the effect of IIc, we decreased IIc to 5.6 +/- 1.1 mmHg
      in five anesthetized sheep. We increased the microvascular filtration rate by
      increasing pulmonary microvascular pressure to 22 +/- 3 mmHg. Then we tagged
      plasma protein with Evans blue dye and estimated sigma d from the lymph and
      plasma dye concentrations. Because tissue protein was not tagged, it did not
      interfere with our sigma d estimate. Our sigma d estimate (0.79 +/- 0.08) was
      much higher than previous estimates in anesthetized animals.

PMID- 9038960
TI  - Progesterone rapidly reduces arterial pressure in ewes.
AB  - Chronic progesterone treatment decreases mean arterial pressure (MAP) and expands
      plasma volume. Evidence now suggests that progesterone metabolites have rapid
      nongenomic actions on the baroreflex. This experiment tests for a rapid effect of
      progesterone on MAP,Na+, arginine vasopressin, and baroreflex sensitivity. Ewes
      were studied during 2-h infusions of vehicle or progesterone at 3 and 6
      micrograms.kg-1.min-1. Infusion of progesterone at 3 micrograms.kg-1.min-1
      resulted in progesterone levels characteristic of ovine pregnancy and
      significantly reduced MAP by the 17th minute, suggesting a nongenomic mechanism.
      However, progesterone infusion at 6 micrograms.kg-1.min-1 produced
      supraphysiological progesterone levels and failed to modify MAP. Overall
      baroreflex sensitivity was not altered by either dose of progesterone, but the
      slope of the tachycardic response to hypotension tended to be attenuated after
      infusion of progesterone at 6 micrograms.kg-1.min-1. We speculate that the lack
      of a simple, linear dose-response effect of progesterone on blood pressure and
      baroreflex sensitivity can be explained by progesterone action at multiple
      receptor populations.

PMID- 9038961
TI  - Hydraulic and diffusional permeabilities of isolated outer medullary descending
      vasa recta from the rat.
AB  - Water permeates many microvessel walls via a pathway shared with small
      hydrophilic solutes and also via an exclusive water pathway. In outer medullary
      descending vasa recta (OMDVR), the relationship between diffusional
      permeabilities to water and sodium indicates the existence of an exclusive water
      pathway and suggests that of a shared pathway. We investigated the latter
      possibility by estimating hydraulic permeability (Lp) and diffusional
      permeability to [3H]raffinose (P(raf)) in isolated, perfused OMDVR. The product
      of hydraulic permeability and osmotic reflexion coefficient of albumin (Lp sigma
      a) was 1.56 +/- 0.19 x 10(-6) cm.s-1.mmHg-1 (n = 28), calculated from transmural
      volume fluxes induced by perfusate-to-bath differences in albumin oncotic
      pressure (delta IIa). P(raf) in the same vessels was 40.1 +/- 7.5 x 10(-5) cm/s
      when delta IIa was zero. In separate experiments, sigma a was at least 0.89 +/-
      0.10 (n = 17). Lp sigma a correlates with P(raf), indicating that OMDVR contain a
      shared pathway for convection driven by delta IIa and for diffusion of small
      hydrophilic solutes.

PMID- 9038962
TI  - Polymorphonuclear leukocytes L-selectin expression decreases as they age in
      circulation.
AB  - We recently reported that L-selectin expression increases on circulating
      polymorphonuclear leukocytes (PMN) during active bone marrow release, which
      suggests that older cells in the circulation have lower levels of L-selectin than
      those recently released from the bone marrow. The present study was designed to
      test the hypothesis that L-selectin expression reduces on PMN as they age in the
      circulation. In vitro studies using flow cytometry showed that PMN L-selectin
      decreased to 14.6 +/- 2.3% of baseline during a 24-h incubation at 37 degrees C.
      To test this hypothesis in vivo, rabbit PMN, labeled in vivo with 5'-bromo-2
      deoxyuridine (PMN-brdU) in donor animals, were infused into recipient rabbits as
      whole blood (n = 5) and followed over 24 h in the circulation with a double
      immunolabeling technique. These results showed that the fraction of the L
      selectin-negative PMN-BrdU in the circulation increased with time (P < 0.001),
      and nearly all of the PMNBrdU in the circulation were L-selectin negative after
      24 h. Removal of L-selectin from the surface of PMN-BrdU with chymotrypsin before
      infusion did not change their rate of removal from the circulation (half-life or
      t 1/2 262 vs. 296 min, P = NS). We conclude that there is a continuous loss of L
      selectin from PMN during their life span in the circulation, which supports the
      hypothesis that L-selectin expression decreases on PMN as they age.

PMID- 9038963
TI  - Function and bioenergetics in isolated perfused trained rat hearts.
AB  - To evaluate the resistance of physiologically hypertrophied hearts to hypoxic
      insult, we quantified the development of functional deficits during hypoxia and
      reoxygenation in hypertrophied hearts from swim-trained female rats and we
      correlated this with assessment of high-energy phosphate (HEP) metabolites from
      simultaneous 31P nuclear magnetic resonance (NMR) measurements. Furthermore, in
      vivo enzymatic studies were carried out with saturation transfer NMR under well
      oxygenated perfusion conditions for both beating and KCl-arrested hearts.
      Finally, in vitro enzymatic assays were performed. During hypoxia, the trained
      hearts exhibited improved systolic and diastolic function compared with hearts
      from sedentary animals. After 16 min of hypoxia, left ventricular (LV) developed
      pressure fell to 9% of baseline in control hearts but to only 21% of baseline in
      trained hearts (P < 0.01). LV diastolic function was also improved by training,
      increasing during hypoxia from a baseline of 10 to 71.0 +/- 3.3 mmHg in control
      hearts and to 55.3 +/- 4.8 mmHg in trained hearts (P < 0.05). Trained hearts also
      showed more rapid and complete recovery of function during reoxygenation and
      greater coronary flow per gram of heart throughout the entire protocol.
      Functional differences were not accompanied by differences in HEP at baseline;
      moreover, ATP and phosphocreatine (PCr) loss during hypoxia was similar between
      control and trained hearts, as was the recovery of PCr during reoxygenation.
      Saturation transfer experiments showed an increase in the forward creatine kinase
      (CrK) rate constant in trained hearts of 18% while beating, whereas in vitro
      enzymatic analysis revealed a 16% increase in the ratio of mitochondrial CrK to
      citrate synthase activity in LV tissue. Thus the relative preservation of
      function in hearts from trained rats could not be accounted for by overall HEP
      levels but may reflect adaptations in the CrK system.

PMID- 9038964
TI  - Cerebral arteriolar dilation to hypoxia: role of prostanoids.
AB  - Experiments addressed the hypothesis that dilator prostanoids contribute to
      maintenance of low cerebral microvascular tone during hypoxia in the newborn.
      Anesthetized newborn pigs equipped with closed cranial windows were used to
      measure responses of pial arterioles (approximately 60 microns) to treatments.
      Hypoxia (Pao2 approximately equal to 25 mmHg) caused dilation of pial arterioles
      (approximately 50% increase in diameter). Hypoxia (5 min) caused an increase in
      cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha concentration from 907
      +/- 171 (normoxia) to 1,408 +/- 213 pg/ml (hypoxia). Pretreatment with
      indomethacin (5 mg/kg) did not affect pial arteriolar dilation to hypoxia.
      Conversely, indomethacin treatment during hypoxia caused a rapid decrease in
      arteriolar diameter to nearly the normoxia diameter within 3 min, returning to
      the original hypoxia diameter by 10 min. Ibuprofen treatment (30 mg/kg) had no
      effect on pial arteriolar diameter during normoxia or hypoxia, and pretreatment
      did not alter dilation to hypoxia. However, pretreatment with ibuprofen abolished
      the constrictor effect of indomethacin given during hypoxia. These data suggest
      that the primary mechanism by which hypoxia produces cerebral vasodilation does
      not involve prostanoids, but prostanoids can contribute to cerebral vasodilation
      in response to hypoxia.

PMID- 9038965
TI  - Regional vascular mechanical properties by 3-D intravascular ultrasound with
      finite-element analysis.
AB  - A method employing intravascular ultrasound (IVUS) and simultaneous hemodynamic
      measurements, with resultant finite element analysis (FEA) of accurate three
      dimensional IVUS reconstructions (3-DR), was developed to estimate the regional
      distribution of arterial elasticity. Human peripheral arterial specimens (iliac
      and femoral, n = 7) were collected postmortem and perfused at three static
      transmural pressures: 80, 120, and 160 mmHg. At each pressure, IVUS data were
      collected at 2.0-mm increments through a 20.0-mm segment and used to create an
      accurate 3-DR. Mechanical properties were determined over normotensive and
      hypertensive ranges. An FEA and optimization procedure was implemented in which
      the elemental elastic modulus was scaled to minimize the displacement error
      between the computer-predicted and actual deformations. The "optimized" elastic
      modulus (Eopt) represents an estimate of the component element material
      stiffness. A dimensionless variable (beta), quantifying structural stiffness, was
      computed. Eopt of nodiseased tissue regions (n = 80) was greater than
      atherosclerotic regions (n = 88) for both normotensive (Norm) and hypertensive
      (Hyp) pressurization: Norm, 9.3 +/- 0.98 vs. 3.5 +/- 0.30; Hyp, 11.3 +/- 0.72 vs.
      8.5 +/- 0.47, respectively (mean +/- SE x 10(6) dyn/cm2; P < 0.01 vs.
      nondiseased). No differences in beta between nondiseased and atherosclerotic
      tissue were noted at Norm pressurization. With Hyp pressurization, beta of
      atherosclerotic regions were greater than nondiseased regions: 21.5 +/- 2.21 vs.
      14.0 +/- 2.11, respectively (P < 0.03). This method provides a means to identify
      regional in vivo variations in mechanical properties of arterial tissue.

PMID- 9038966
TI  - Chemoreceptor dependence of very low frequency rhythms in advanced chronic heart
      failure.
AB  - Factors responsible for very low frequency oscillations (VLF; cycle > 30 s) in
      the cardiovascular system remain obscure. We tested the hypothesis that increased
      peripheral chemosensitivity is important in the pathogenesis of VLF oscillations
      in patients with chronic heart failure (CHF). Fourteen male patients with stable,
      moderate to severe CHF (age 60 +/- 1.1 yr, ejection fraction 23 +/- 11%) and
      reproducible VLF oscillations in heart rate underwent a protocol consisting of
      three consecutive 20-min phases during which they breathed air, hyperoxia (O2 via
      mask, 60% O2 concn), and air again. Autoregressive spectral analysis of R-R
      intervals, blood pressure, and respiration was used to quantify total oscillatory
      power (TP), VLF, low (0.04-0.15 Hz)- and high (0.15-0.40Hz)-frequency power, and
      the coherence between these signals. Peripheral chemosensitivity was studied by
      assessing the ventilatory response to hypoxia using transient inhalations of pure
      N2. Discrete VLF rhythms were seen in R-R intervals in all 14 patients, in blood
      pressure in 7 of 14, and in respiration in 8 of 14 patients. A significant
      coherence (> 0.5) between heart rate and systolic blood pressure within the VLF
      band with mean phase value of -140 degrees, suggesting an antibaroreflex
      relationship, was seen in six subjects. Transient hyperoxia abolished the VLF
      oscillations in most subjects (12 of 14 in R-R intervals) and decreased R-R
      variability power within the VLF band. This response significantly correlated
      with peripheral chemoreceptor sensitivity (r = 0.77, P = 0.014). This study
      suggests that in CHF, enhanced peripheral chemoreceptor activity may facilitate
      slow oscillations in the cardiorespiratory signals.

PMID- 9038969
TI  - Anterior and posterior left ventricular sarcomere lengths behave similarly during
      ejection.
AB  - Previous studies of regional differences in myocardial deformation between the
      anterior and posterior walls of the canine left ventricle were based on strain,
      which is not an absolute measure of deformation. We thus compared sarcomere
      lengths at anterior and posterior sites during ejection in isolated dog hearts.
      Cineradiographic imaging of regional deformation with radiopaque markers
      implanted near the midwall in five hearts and just below the epicardium in six
      hearts, combined with postmortem histology, allowed sarcomere length
      reconstruction throughout the cardiac cycle. The amount of sarcomere shortening
      accompanying left ventricular ejection was similar in both walls of the left
      ventricle for sarcomeres located at epicardial and midwall sites. The mean
      sarcomere length (taken at the middle of the ejecting range) was also similar
      between the anterior and posterior sites when averaged over all hearts. The
      similarity of sarcomere function held not only at end systole but throughout
      ejection and over wide ranges of ventricular pre- and afterloads. Hence
      functional measurements of relative myocardial shortening may not be indicative
      of regional sarcomere length heterogeneity.

PMID- 9038967
TI  - System identification of closed-loop cardiovascular control: effects of posture
      and autonomic blockade.
AB  - We applied system identification to the analysis of fluctuations in heart rate
      (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to
      characterize quantitatively the physiological mechanisms responsible for the
      couplings between these variables. We characterized two autonomically mediated
      coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory
      sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the
      blood pressure wavelet generated with each cardiac contraction (circulatory
      mechanics) and the direct mechanical effects of respiration on blood pressure
      (ILV-->ABP)]. We evaluated the method in humans studied in the supine and
      standing postures under control conditions and under conditions of beta
      sympathetic and parasympathetic pharmacological blockades. Combined beta
      sympathetic and parasympathetic blockade abolished the autonomically mediated
      couplings while preserving the mechanically mediated coupling. Selective
      autonomic blockade and postural changes also altered the couplings in a manner
      consistent with known physiological mechanisms. System identification is an
      "inverse-modeling" technique that provides a means for creating a closed-loop
      model of cardiovascular regulation for an individual subject without altering the
      underlying physiological control mechanisms.

PMID- 9038968
TI  - Carnosine is a novel peptide modulator of intracellular calcium and contractility
      in cardiac cells.
AB  - Myocardial contractile failure is a common cause of morbidity and mortality in
      patients with ischemic heart disease and systemic inflammatory states such as
      sepsis. Accumulating evidence indicates that contractile failure is associated
      with dysregulation of myoplasmic calcium levels. In a search for biochemical
      causes for contractile dysfunction, we found that the dipeptide carnosine
      improves cardiac contractility and tested the possibility that carnosine plays a
      role in the regulation of intracellular calcium. Carnosine increased
      contractility in a dose-dependent manner (1-10 mM) in isolated perfused rat
      hearts. and it also increased free intracellular calcium levels in isolated
      myocytes. Carnosine increased myocyte tension via calcium release from the
      ryanodine receptor calcium release channel in skinned myocardial fibers and
      increased open-state probability and dwell time of the isolated ryanodine
      receptor calcium release channel in lipid bilayers. In addition. we report that
      carnosine sensitizes the contractile proteins so calcium. These results suggest a
      novel role for carnosine as a modulator of intracellular calcium and
      contractility in cardiac tissue.

PMID- 9038970
TI  - Chronic opiate-receptor inhibition in experimental congestive heart failure in
      dogs.
AB  - Acute administration of opiate-receptor antagonists has previously been shown to
      improve cardiac output aortic blood pressure, systolic ventricular performance,
      and the baroreflex function in conscious dogs with right-sided congestive heart
      failure (RHF). However, whether similar changes occur after chronic opiate
      receptor inhibition in congestive heart failure is not known. To determine the
      chronic effects of opiate-receptor antagonism on RHF, we administered naltrexone
      (200 mg/day), a long-acting, orally active opiate-receptor blocking agent, to RHF
      and sham-operated animals for 6 wk. Naltrexone had no effects on resting heart
      rate, right atrial pressure, aortic pressure, or cardiac output in RHF dogs but
      increased the first derivative of right and left ventricular pressure with
      respect to time (dP/dt) at rest and improved the dP/dt response to isoproterenol.
      The inotropic responses to isoproterenol and forskolin in isolated right
      ventricular trabeculate muscle also were improved by chronic naltrexone in RHF.
      Myocardial beta-receptor density was reduced in the failing right ventricle
      compared with the control (58 +/- 3 vs. 108 +/- 6 fmol/mg protein, P < 0.01) but
      was unaffected by addition of naltrexone. Finally, naltrexone prevented the
      decline in baroreflex sensitivity that occurred in RHF (-0.2 +/- 0.5 vs. -6.0 +/-
      0.5 ms/mmHg, P < 0.01). These effects of naltrexone did not occur in the
      shamoperated animals. Chronic opiate-receptor blockade with naltrexone attenuates
      the development of reduced adrenergic inotropic responsiveness and baroreflex
      subsensitivity that occur in RHF. Because there was a similar improvement in the
      forskolin response in the absence of significant alterations in myocardial beta
      adrenoceptor density after naltrexone treatment, the improvement in
      adrenergically mediated inotropic effects probably is mediated via a postreceptor
      mechanism.

PMID- 9038971
TI  - Selective activation of vasomotor component of SAP spectrum by nucleus
      reticularis ventrolateralis in rats.
AB  - We evaluated the contribution of the rostral nucleus reticularis ventrolateralis
      (NRVL) to the vasomotor component in the spectrum of systemic arterial pressure
      (SAP) signals by quantifying the transfer function between electrical stimulation
      of this medullary nucleus and the SAP response. Sprague-Dawley rats anesthetized
      with pentobarbital sodium, paralyzed with pancuronium, and mechanically
      ventilated were used. Broad-band stimulation of the NRVL with computer-generated
      rectangular current pulses (10-50 microA, 1 ms), at a mean spike rate of 50
      pulses/s and randomized modulation frequency of 0-3 Hz, elicited a site-specific
      and intensity-related pressor response. Intriguingly, the corresponding
      autospectrum of SAP signals exhibited prevailing power density only in the lower
      frequency range (0-0.8 Hz). This low-pass response characteristic was confirmed
      by the observation that 90% of the total magnitude of transfer function between
      NRVL stimulation and SAP response concentrated between 0 and 0.6 Hz. The
      magnitude of NRVL-SAP transfer function was significantly reduced by phentolamine
      or prazosin but appreciably enhanced by yohimbine. We conclude that the NRVL may
      contribute to the very-low (0-0.25 Hz)- and low (0.25-0.8 Hz)-frequency
      components of the SAP spectrum, which are belived to reflect sympathetic
      modulation on vasomotor activity via alpha-adrenergic neurotransmission.

PMID- 9038972
TI  - Endothelial vasoconstrictor prostanoids modulate contractions to acetylcholine
      and ANG II in Ren-2 rats.
AB  - We investigated vascular function in mouse Ren-2 transgenic rats with
      hypertension. Mesenteric resistance arteries of transgenic and Sprague-Dawley
      rats (controls) were isolated at ages 6 and 12 wk and suspended in myographs for
      isometric tension recording. Systolic blood pressure was higher in transgenic
      than control rats (P < 0.05). Contractions to norepinephrine and endothelin-1
      were comparable in transgenic and control rats, but the sensitivity decreased
      with age in both strains (P < 0.05). Contractions to angiotensin I were
      comparable in 6-wk-old transgenic rats and controls, but the response to
      angiotensin I was more pronounced in transgenic rats at 12 wk of age.
      Contractions to angiotensin II were higher in transgenic rats and decreased with
      age in both strains. Preincubation with the cyclooxygenase inhibitor
      meclofenamate or the thromboxane receptor antagonist SQ-30741 blunted the
      response only in 6-wk-old transgenic rats. In quiescent vascular rings,
      acetylcholine evoked endothelium-dependent contractions after inhibition of
      nitric oxide formation by N omega-nitro-L-arginine methyl ester only in
      transgenic rats. These contractions were inhibited by SQ-30741 (P < 0.05) but not
      by the thromboxane synthase inhibitor CGS-13080. Contractions to the thromboxane
      analogue U-46619 were comparable in both strains at the age of 6 wk; sensitivity
      was increased in transgenic rats at 12 wk (P < 0.05). In conclusion, in
      mesenteric resistance arteries of Ren-2 transgenic rats I) contractions to
      angiotensin I and II but not to norepinephrine and endothelin-1 are increased,
      and 2) acetylcholine as well as angiotensin II modulate endothelium-dependent
      contractions mediated by prostaglandin H2. These alterations together with
      increased sensitivity to thromboxane could contribute to maintenance as well as
      to impaired tissue perfusion of this form of hypertension.

PMID- 9038973
TI  - Magnesium is a cerebrovasodilator in newborn piglets.
AB  - We tested the hypothesis that, in newborn piglets, magnesium results in a dose
      dependent prostanoid-mediated cerebrovasodilation. Pial arterioles (50-200
      microns in diameter) were serially measured, and cortical subarachnoid
      cerebrospinal fluid (CSF) was collected for radioimmunoassay of 6
      ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, hydrolysis product of
      prostacyclin) and thromboxane B2 (TxB2, metabolite of thromboxane A2) before and
      after CSF containing 1.2, 2.4, 4.8, and 9.6 mM MgCl2 was suffused over the
      parietal cortex under a closed cranial window in twelve 2- to 4-day-old piglets.
      Magnesium suffusion resulted (P < 0.05) in a dose-dependent pial arteriolar
      vasodilation. The increase in vessel diameter was greater (P < 0.001) with 2.4,
      4.8, and 9.6 mM than with 1.2 mM concentration of magnesium. The increase in
      vessel diameter with 9.6 mM was also greater (P < 0.001) than with the 2.4 mM
      concentration of magnesium. Magnesium suffusion did not result in changes in
      cortical CSF prostanoid concentrations. The effect of intravenous indomethacin (5
      mg/kg) on cyclooxygenase inhibition in the pial arterioles was confirmed by a 24
      +/- 3% decrease in vessel diameter at the baseline (1.2 mM) magnesium
      concentration. In contrast, cyclooxygenase inhibition with intravenous
      indomethacin did not attenuate the magnesium-induced cerebrovasodilation. We
      conclude that in new born piglets magnesium suffusion over the parietal cortex
      results in a dose-dependent cerebrovasodilation that is most likely not mediated
      by prostanoids.

PMID- 9038974
TI  - Continuous low-dose NO inhalation does not prevent monocrotaline-induced
      pulmonary hypertension in rats.
AB  - We determined whether vasodilator doses of inhaled nitric oxide (NO) prevented
      the progression of pulmonary hypertension (PH) and vascular changes in
      monocrotaline-induced PH. Short-term NO inhalation in rats 3 wk after the
      injection of monocrotaline reduced mean pulmonary artery pressure (PAP) from 30.7
      +/- 2.2 (SE) to 26.4 +/- 1.4 mmHg at 10 parts per million (ppm) and from 30.2 +/-
      1.3 to 25.8 +/- 1.4 mmHg at 40 ppm. There were no differences among rats exposed
      to air only and rats exposed to 10 ppm of NO for 19 days after a single
      subcutaneous injection of monocrotaline, in mean PAP (34.3 +/- 1.9 mmHg air vs.
      32.8 +/- 1.4 mmHg NO), right ventricular hypertrophy (RVH), medial wall thickness
      (MWT) of muscular arteries, and the percentage of muscularized arteries at
      alveolar wall (%AW) and duct (%AD) level. Additional groups exposed to air only
      and 40 ppm of NO for 19 days again showed no difference in mean PAP, RVH, MWT,
      and %AD, except that this dose slightly reduced %AW (60.6 +/- 3.4% air vs. 46.9
      +/- 5.2% NO, P = 0.04). Urine nitrate (NO3) level was higher in rats that had
      inhaled NO. In contrast to chronic hypoxic PH, vasodilator doses of NO inhalation
      did not prevent the development of PH in this malignant form of experimental PH.

PMID- 9038975
TI  - Fluid resuscitation with O2 vs. non-O2 carriers after 2 h of hemorrhagic shock in
      conscious hamsters.
AB  - Efficacy of a cell-free o-raffinose cross-linked and oligomerized hemoglobin
      (Hemo-link) solution in restoring macro- and microcirculatory conditions after 2
      h of hemorrhagic shock (40 mmHg) was compared with conventional treatment with
      autologous whole blood, Ringer lactate (RL), and Dextran 70. Studies were
      conducted in the dorsal skinfold microcirculation of conscious hamsters. Initial
      infusion was equivalent to shed blood volume (SBV) for RL and 50% of SBV for
      remaining solutions. After 2 h all animals received blood at 50% of SBV. Vessel
      diameter, functional capillary density, microvascular red blood cell velocity,
      and flow were measured. Arteriolar, venular, and tissue PO2 were determined by
      phosphorescence decay. Systemic parameters included mean arterial blood pressure,
      heart rate, arterial blood gases, pH, and base excess. Autologous whole blood and
      Hemolink, but not Dextran 70 and RL, restored mean arterial blood pressure,
      systemic blood gas, and metabolic parameters. Tissue PO2 recovered to 40-50% with
      blood and Hemolink but remained significantly lower (10-15% of control) with
      Dextran 70 and RL. Initial volume replacement after shock with blood or Hemolink
      yields equivalent macro- and microhemodynamic improvements not attainable with
      non-O2-carrying plasma expanders.

PMID- 9038976
TI  - Membrane lipid order of human red blood cells is altered by physiological levels
      of hydrostatic pressure.
AB  - The effect of hydrostatic pressure at levels applied in diving or hyperbaric
      treatment (thus considered "physiological") on the order of lipid domains in
      human red blood cell (RBC) membrane was studied. Membrane order was determined by
      measuring 1) the fluorescence anisotropy (FAn) of lipid probes, 2) the resonance
      energy transfer from tryptophan to lipid probes, and 3) spectral shifts in
      Laurdan fluorescence emission. It was found that the application of mild pressure
      (< 15 atm) 1) increased, selectively, the FAn of lipid probes that monitor the
      membrane lipid core, 2) increased the tryptophan FAn, 3) increased the resonance
      energy transfer from tryptophan to lipid probes residing in the lipid core, and
      4) induced changes in the Laurdan fluorescence spectrum, which corresponded to
      reduced membrane hydration. It is proposed that the application of pressure of
      several atmospheres increases the phase order of membrane lipid domains,
      particularly in the proximity of proteins. Because the membrane lipid order
      ("fluidity") of RBCs plays an important role in their cellular and rheological
      functions, the pressure-induced alterations of the RBC membrane might be
      pertinent to microcirculatory disorders observed in humans subjected to elevated
      pressure.

PMID- 9038978
TI  - Capacitive function of the heart: influence of acute changes in heart volume on
      mean right atrial pressure.
AB  - Net transfer of blood volume into or out of the cardiac chambers should have the
      same effect on central venous pressure as does transfer of an equal volume of
      blood to or from peripheral organs (e.g., spleen, or liver). We studied five
      pentobarbital sodium-anesthetized open-chest pigs (20-23 kg) to determine whether
      a reduction in the time-averaged volume of blood contained in the heart, induced
      by rapid atrial pacing, can raise right atrial pressure. A central premise of our
      study is that the mean value of right atrial pressure is acutely governed by the
      volume of blood that distends the central veins, and that atrial contractions
      primarily determine how atrial pressure varies about its mean value. To prevent
      changes in cardiac output from altering central blood volume and pressure,
      cardiac output during rapid pacing (2.36 +/- 0.18 l/min) was made to equal the
      resting output (2.35 +/- 0.16 l/min). This was achieved by selecting a rate of
      pacing at which the tendency for more frequent cardiac contractions to raise
      cardiac output was counterbalanced by the decrease in stroke volume induced by
      rapid pacing. Autonomic reflex mechanisms were attenuated by pharmacological
      blockade. Mean arterial pressure was minimally affected in the transition from a
      normal sinus rhythm (89 +/- 6 beats/min) to rapid atrial pacing (165 +/- 7
      beats/min) in four pigs. Mean right atrial pressure rose abruptly from 2.8 +/-
      0.5 mmHg during normal sinus rhythm to 3.5 +/- 0.5 mmHg (P = 0.015) at the onset
      of rapid pacing in these four pigs, presumably owing to decreased cardiac blood
      volume and a reciprocal expansion of central venous volume. In the fifth pig, a
      reduction in cardiac output induced by tachycardia led to a larger rise in mean
      right atrial pressure than did a reduction in cardiac output induced by
      bradycardia, presumably because tachycardia reduces cardiac blood volume whereas
      bradycardia raises cardiac volume. We conclude that the heart may play an
      important role in maintaining or raising its own filling pressure when heart rate
      rises.

PMID- 9038977
TI  - Ischemic preconditioning and intracellular pH: a 31P NMR study in the isolated
      rat heart.
AB  - The aim of these studies was to investigate whether manipulation of intracellular
      pH affects preconditioning in isolated buffer-perfused rat hearts. Control and
      preconditioned [PC; 3 min of ischemia (I) + 3 min of reperfusion (R) + 5 min of I
      + 5 min of R or 4 x (5 min of I + 5 min of R)] hearts were subjected to two
      different protocols expected to alter intracellular pH during the sustained
      ischemic insult: 1) increased extracellular buffering capacity with the addition
      of 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to the
      buffer to alleviate acidosis and 2) increased preischemic glycogen content to
      exacerbate acidosis. All hearts were subjected to 40 min of I + 40 min of R. 31P
      nuclear magnetic resonance was used to measure ATP, phosphocreatine, Pi, and
      intracellular pH. Despite a significantly better recovery of function in all PC
      groups, there were no significant differences in intracellular pH (rate-pressure
      product = 60 +/- 5, 66 +/- 10, 42 +/- 5, and 57 +/- 8% of baseline in PC, 4 x 5
      PC, PC + HEPES, and PC fasted hearts, respectively, compared with 36 +/- 9, 17 +/
      7, and 20 +/- 10% of baseline in control, control + HEPES, and control fasted
      hearts, respectively; pH at end ischemia: control, 6.31 +/- 0.02; PC, 6.35 +/-
      0.03; 4 x 5 PC, 6.35 +/- 0.04; control + HEPES, 6.40 +/- 0.10; PC + HEPES, 6.56
      +/- 0.07: control fasted, 6.46 +/- 0.03; PC fasted, 6.43 +/- 0.01). No
      significant differences were observed among groups in ATP, phosphocreatine, or Pi
      on reperfusion. Thus the mechanism of preconditioning in glucose-perfused hearts
      does not depend on an alleviation of intracellular acidosis during the sustained
      ischemic period. Furthermore, under the conditions of this study, intracellular
      pH during ischemia did not predict functional recovery on reperfusion.

PMID- 9038979
TI  - Neuronal NOS-derived NO plays permissive role in cerebral blood flow response to
      hypercapnia.
AB  - The aim of the present study was to determine whether neuronal nitric oxide
      synthase (nNOS)-derived nitric oxide (NO) plays a permissive role in the
      regulation of cerebral blood flow (CBF) response to hypercapnia. To this end, we
      examined whether the administration of NO donors could reestablish the regional
      CBF (rCBF) response to hypercapnia after nNOS inhibition with 7-nitroindazole (7
      NI). Rats were anesthetized with 1% halothane, and rCBF in the cortex was
      measured by laser-Doppler flowmetry. The administration of 7-NI (40 mg/kg ip)
      decreased resting rCBF by 17 +/- 5% (n = 6, P < 0.05) and attenuated the rCBF
      response to hypercapnia by 30 +/- 8% in comparison with the response seen in rats
      treated with the vehicle (peanut oil) alone. Intracerebroventricular
      administration of NO donors, sodium nitroprusside (SNP; n = 7) and (Z)-1-[N
      methyl-N-[6(N-methylammoniohexyl)aminol]]diazen+ ++-1-ium-1,2-diolate (MAHMA
      NONOate; n = 6) in a dose of 0.1-1 nmol/min after 7-NI restored both resting rCBF
      to baseline and the vasodilatory response to hypercapnia. In contrast,
      intravenous infusion of SNP (0.05-0.5 nmol/min, n = 6) or intracerebroventricular
      administration of an NO-independent vasodilator, the stable prostaglandin I2
      analog iloprost (0.01-0.1 nmol/min, n = 6), after 7-NI failed to restore the
      vasodilatory response to hypercapnia, despite the fact that it restored the
      resting rCBF to baseline. nNOS activity, assessed by the conversion of labeled
      arginine to citrulline, was inhibited by 70 +/- 7% after the administration of 7
      NI. These findings confirm that the selective inhibition of nNOS decreases
      resting rCBF and attenuates the rCBF response of hypercapnia. They further
      indicate that the repletion of intraparenchymal NO allows the hypercapnic
      cerebrocortical vasodilation to occur. Therefore, it is suggested that the nNOS
      derived NO plays a permissive role in the CBF response to hypercapnia.

PMID- 9038980
TI  - Changes in myocardial blood volume with graded coronary stenosis.
AB  - Vasodilation of microvessels distal to a stenosis results in an increase in
      myocardial blood volume (MBV). The purpose of this study was to examine the
      changes in MBV induced by graded coronary artery stenoses by using myocardial
      contrast echocardiography (MCE). Accordingly, 21 dogs underwent progressive
      stenosis of a coronary artery in a random order, the severity of which was judged
      by the pressure distal to it. Total myocardial blood flow (MBF) to the bed distal
      to the artery (both anterograde and collateral) was measured by injection of
      radiolabeled microspheres into the left atrium. In seven dogs, anterograde and
      total MBF were measured at each stenosis stage by injection of different
      microspheres into the left atrium and directly into the coronary artery,
      respectively. MBV was calculated by dividing MBF by the mean transit rate of
      microbubbles injected directly into the coronary artery during MCE. The perfusion
      bed size of the artery was also measured by MCE. Our major findings are as
      follows: 1) there is a nonlinear increase in MBV with increasing degrees of
      coronary stenosis until the coronary stenosis becomes critical; 2) at moderate
      levels of coronary stenosis, MBV remains constant despite ongoing autoregulation
      because of reduction in the size of the perfusion bed supplied by the stenotic
      vessel; and 3) after exhaustion of autoregulation, a decrease in MBV is noted
      with increasing levels of stenosis. We conclude that assessment of MBV provides
      insights into myocardial perfusion distal to a coronary stenosis above and beyond
      that provided by the measurement of MBF alone.

PMID- 9038981
TI  - Vascular smooth muscle cells on Matrigel as a model for LPS-induced
      hypocontractility and NO formation.
AB  - Treatment of vascular tissue with low levels of lipopolysaccharide (LPS) induces
      nitric oxide synthase (NOS) activity and diminishes vascular contractility.
      However, in cultured vascular smooth muscle cells (VSMC), very high doses of LPS
      or the combination of LPS with cytokines are required for the induction of nitric
      oxide (NO) formation. The aims of this study were to establish a cell model to
      investigate LPS-induced hypocontractility and NO production and to test the
      hypothesis that responses of VSMC to LPS are differentiation regulated. We used
      Matrigel basement membrane matrix to maintain VSMC differentiation and found that
      VSMC cultured on Matrigel retained significant contractility in response to KCl
      stimulation. Incubation of VSMC with low levels of LPS(1-100 ng/ml) induced NOS
      mRNA and protein, induced NO production, and decreased cell contractility in a
      time- and dose-dependent fashion. The NOS inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME) partially restored LPS-treated VSMC contractility, whereas L
      arginine reversed the contractility-restoring effect of L-NAME. These results
      suggest that VSMC grown on Matrigel are a useful experimental model for
      investigations into signal transduction mechanisms responsible for LPS-induced
      vascular hypocontractility.

PMID- 9038982
TI  - Cardiomyopathy induced by cardiac Gs alpha overexpression.
AB  - The goal of this study was to determine whether chronic endogenous sympathetic
      stimulation resulting from the overexpression of cardiac stimulatory G protein
      alpha subunit (Gs alpha) in transgenic mice (15.3 +/- 0.1 mo old) resulted in a
      clinical picture of cardiomyopathy. The left ventricular ejection fraction,
      measured by echocardiography, was reduced in older mice with Gs alpha
      overexpression (50.4 +/- 5.4%) compared with age-matched control mice (70.9 +/-
      1.6%; P < 0.05). When ejection fractions were compared at similar heart rates,
      the Gs alpha mice exhibited a greater left ventricular end-diastolic dimension
      than control mice (4.3 +/- 0.2 vs. 3.7 +/- 0.1 mm; P < 0.05). Baseline heart
      rates were elevated in conscious Gs alpha mice (722 +/- 27 beats/min; n = 5)
      compared with control mice (656 +/- 28 beats/min; n = 5). Moreover,
      electrocardiographic monitoring demonstrated a high incidence of arrhythmias.
      Increased mortality compared with control mice (31.6 vs. 3.0%; P < 0.01) was also
      observed. Thus older mice with Gs alpha overexpression exhibit many of the
      features of dilated cardiomyopathy. This study supports the concept that chronic
      sympathetic stimulation over an extended period of time, i.e., over the life of
      an animal, is deleterious and actually may result in cardiomyopathy.

PMID- 9038983
TI  - Transgenic manipulation of beta-adrenergic receptor kinase modifies cardiac
      myocyte contraction to norepinephrine.
AB  - To determine the direct functional significance of the beta-adrenergic receptor
      (AR) kinase 1 (beta ARK1) on myocardial performance in the absence of tonic
      sympathoadrenal neural activation and mechanical loading, we measured the
      contractile responses to acute beta 1-AR stimulation in left ventricular myocytes
      isolated from nontransgenic control (NTG) and transgenic mice overexpressing
      either beta ARK1 (TG beta K12) or a beta ARK1 inhibitor (TGMini27). Contractile
      response to five concentrations (10(-8)-10(-7) M) of the beta 1-AR agonist
      norepinephrine (NE) plus prazosin (10(-6) M) was measured after a 60-s rest,
      i.e., rested-state contraction (RSC), and during steady-state contraction (SSC)
      stimulation at 0.5 Hz (23 degrees C). At baseline, resting cell length was
      significantly greater in TG beta K12 myocytes (P < 0.05); however, there were no
      significant differences in RSC or SSC among NTG, TG beta K12, or TG Mini27 mice.
      On the other hand, both the dose-response curve and kinetics for the NE-induced
      SSC response normalized to RSC (SSC/RSC) were significantly different among
      experimental groups (P < 0.001). Specifically, maximal SSC induced by NE in
      myocytes isolated from TG beta K12 was only 70% of the response observed in NTG
      cells and 50% of the response measured in TGMini27. These data suggest that 1) in
      the absence of circulating catecholamines or basal sympathetic tone, beta ARK1
      actions in single myocytes are minimal, and 2) substantial functional beta ARK1
      modulation of beta 1-AR signaling occurs in cardiac myocytes even during short
      term beta 1-AR stimulation. These results are consistent with a role for agonist
      induced phosphorylation and desensitization of cardiac beta 1-ARs by beta ARK1 in
      single myocytes and highlight the potential functional importance of beta ARK1 as
      a critical determinant of the cardiac beta 1-AR contractile response.

PMID- 9038984
TI  - Effects of 2-deoxy-D-glucose and insulin on plasma glucose levels and behavioral
      thermoregulation of toads.
AB  - The present study was designed to test the hypothesis that hypoglycemia induces
      hypothermia in ectotherms and to elucidate the mechanisms responsible for
      behavioral hypothermia. Behavioral hypothermia is a stress response that occurs
      in organisms ranging from protozoans to mammals, but very little is known about
      the cellular mechanisms involved. Toads equipped with a temperature probe were
      tested in a thermal gradient (10-40 degrees C). Insulin was used to reduce plasma
      glucose levels, and an inhibitor of glucose utilization, 2-deoxy-D-glucose (2
      DG), was used to cause intracellular glucopenia. Insulin injections into the
      dorsal lymph sac caused significant reductions of both plasma glucose levels and
      body temperature. To determine if the response was mediated by extracellular
      glucose receptors or an intracellular mechanism. 2-DG was also injected into the
      lymph sac. 2-DG caused a similar drop in body temperature and a marked increase
      in plasma glucose. To assess the role of central thermoregulatory mechanisms, a
      smaller dose of 2-DG was injected into the fourth cerebral ventricle or the lymph
      sac. Intracerebroventricular injection of 2-DG caused a decrease in body
      temperature despite elevated circulating glucose levels, whereas injection into
      the lymph sac caused no significant change. The data indicate that exclusion of
      glucose from central rather than peripheral sites plays a major role in the
      hypoglycemia-induced behavioral hypothermia and that intracellular mechanisms
      rather than extracellular glucose receptors are involved in this response.
      Hypothermia may be a beneficial response to hypoglycemia in toads because it
      dampens cellular oxidative demands during glucose deprivation.

PMID- 9038985
TI  - Mechanisms of pHi recovery from NH4Cl-induced acidosis in anoxic isolated turtle
      heart: a 31P-NMR study.
AB  - Mechanisms of intracellular pH (pHi) recovery from NH4Cl-induced acidosis were
      investigated on isolated perfused hearts of the turtle, Chrysemys picta bellii,
      using 31P nuclear magnetic resonance (NMR) spectroscopy at 20 degrees C. A major
      goal was to assess the activity of these mechanisms under anoxic conditions.
      Based on calculated buffer capacity and a pHi recovery range at 20 degrees C of
      6.75-6.95 (normal pHi 7.2-7.4), mean H' efflux rate during perfusion with CO2
      free N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES)-buffered Ringer
      was only 15% (normoxia) and 25% (anoxia) of that with HCO3-buffered Ringer. With
      HCO3 solution, anoxic H1 efflux rate was approximately 50% of normoxia (0.333 vs.
      0.645 mmol.l-1.min-1), but in TES solution, H1 efflux rate was unaffected by
      anoxia. To further characterize the transporters, we used blockers [the Na(+)-H+
      antiport inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) and the anion
      exchanger inhibitor 4,4'diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS)], ion
      substitution, and temperature change. EIPA (10 microM) inhibited H+ efflux rate
      by 40% in anoxic TES solution; DIDS (0.5 mM) blocked H+ efflux rate by 85% in
      anoxic HCO3 solution. No pHi recovery was observed in either normoxic or anoxic
      Na(+)-free solutions, but normal recovery was observed in the absence of
      extracellular Cl-. Recovery of pHi occurred 2-3 times faster at 30 degrees C than
      at 20 degrees C. ATP was unaffected by any manipulation in this study, whereas
      creatine phosphate (CP) fell during anoxia, and both CP and mechanical
      performance changed in parallel to pHi. We conclude that pHi regulation functions
      during anoxia, although at a reduced rate, and that recovery from acidosis is
      dominated, during both normoxia and anoxia, by a DIDS-sensitive Na+ and HCO3(-)
      dependent mechanism, whereas EIPA-sensitive Na(+)-H+ antiport plays a less
      important role.

PMID- 9038986
TI  - Lactation alters the effects of conditioned stress on immune function.
AB  - During lactation, endocrine function is altered and stress responses are
      dampened. Stress effects on immune function are partially determined by endocrine
      factors; therefore, we assessed whether stress similarly alters immune function
      during lactation. Sprague-Dawley rats were conditioned by exposure to a tone
      paired with foot shock (2 sessions, 16 shocks each) prior to breeding or were
      left undisturbed. Lactating (day 10) (Lac) and nonlactating diestrous virgin
      controls (C) were killed immediately after reexposure to the tone or removal from
      their home cage. Plasma corticosterone stress responses were dampened in Lac
      relative to C animals. Peripheral blood lymphocyte proliferation to T cell
      receptor antibody stimulation was reduced to a similar extent in both
      experimental groups. Conditioned stress reduced splenocyte proliferation and
      increased nitrite accumulation in C animals, but not in Lac animals. Mesenteric
      lymph node lymphocyte proliferation was significantly increased after stress in
      Lac compared with C animals. Both plasma interleukin-6 (IL-6) and
      phytohemagglutinin-stimulated splenic IL-6 production were increased in Lac
      animals compared with C animals after stress exposure. These data indicate that
      stress-induced alterations may be determined by different regulatory mechanisms
      within immune compartments and that these effects depend on the physiological
      state of the organism.

PMID- 9038987
TI  - Role of central ANG II receptors in stress-induced cardiovascular and
      hyperthermic responses in rats.
AB  - The present study was carried out using a biotelemetry system to investigate
      whether central angiotensin II (ANG II) is involved in stress-induced
      cardiovascular and body temperature responses in rats. Intracerebroventricular
      injections of the nonselective ANG II-receptor antagonist saralasin and of the
      ANG II AT1-receptor antagonist losartan attenuated both the heart rate and
      pressor responses to immobilization stress in a dose-dependent manner. The
      elevation of plasma norepinephrine and epinephrine induced by immobilization
      stress was also suppressed by central ANG II-receptor blockade, suggesting a
      general attenuation of stress-induced sympathetic nervous and adrenomedullary
      activity by central ANG II-receptor blockade. The hyperthermia induced by
      immobilization stress was attenuated by central ANG II AT1-receptor blockade in a
      dose-dependent manner. The effects of central saralasin on the blood pressure
      response induced by immobilization stress were greater in Wistar-Kyoto rats than
      in spontaneously hypertensive rats. The present results suggest that central ANG
      II AT1-receptors are involved in expression of the tachycardia and hyperthermia,
      as well as the pressor response, induced by immobilization stress.

PMID- 9038988
TI  - Contractile properties of rat, rhesus monkey, and human type I muscle fibers.
AB  - It is well known that skeletal muscle intrinsic maximal shortening velocity is
      inversely related to species body mass. However, there is uncertainty regarding
      the relationship between the contractile properties of muscle fibers obtained
      from commonly studied laboratory animals and those obtained from humans. In this
      study we determined the contractile properties of single chemically skinned
      fibers prepared from rat, rhesus monkey, and human soleus and gastrocnemius
      muscle samples under identical experimental conditions. All fibers used for
      analysis expressed type I myosin heavy chain as determined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Allometric coefficients for type I
      fibers from each muscle indicated that there was little change in peak tension
      (force/fiber cross-sectional area) across species. In contrast, both soleus and
      gastrocnemius type I fiber maximal unloaded shortening velocity (Vo), the y
      intercept of the force-velocity relationship (Vmax), peak power per unit fiber
      length, and peak power normalized for fiber length and cross-sectional area were
      all inversely related to species body mass. The present allometric coefficients
      for soleus fiber Vo (-0.18) and Vmax (-0.11) are in good agreement with published
      values for soleus fibers obtained from common laboratory and domesticated
      mammals. Taken together, these observations suggest that the Vo of slow fibers
      from quadrupeds and humans scale similarly and can be described by the same
      quantitative relationships. These findings have implications in the design and
      interpretation of experiments, especially those that use small laboratory mammals
      as a model of human muscle function.

PMID- 9038989
TI  - Depletion of linoleate induced by weight cycling is independent of extent of
      calorie restriction.
AB  - Recent epidemiological studies have suggested that weight cycling induced by
      repeated dieting over time may increase the risk of cardiovascular disease. It is
      speculated that the increased mortality from coronary heart disease for people
      with a history of excessive weight cycling could be attributed to change in lipid
      metabolism. Previous studies have demonstrated that repeated cycling of 100% food
      restriction followed by ad libitum refeeding caused a depletion of linoleate and
      alpha-linolenate in rats. The objective of the present study was to test the
      hypothesis that the weight cycling-induced reduction in linoleate and alpha
      linolenate is independent of extent of calorie restriction. Two consecutive
      weight cycles in three experiments were induced by 100% calorie restriction, 60%
      calorie restriction, and 36% calorie restriction, respectively, followed by ad
      libitum refeeding. As the consequence of the two weight cycles, linoleate and
      linolenate were decreased, whereas myristate, palmitate, and palmitoleate were
      proportionally increased in carcass and adipose tissue lipids. The results of all
      three experiments showed a preferential depletion of linoleate and alpha
      linolenate without changes in final body weight, total body fat, and adipose
      tissue pads in the weight-cycled rats. In addition, the triacylglycerol species
      profile in the adipose tissue of weight-cycled rats was significantly remodeled,
      with a proportional depletion of linoleate-enriched triacylglycerol species (LLL,
      LLO, and LLP, where L, O, and P are linoleic, oleic, and palmitic acid,
      respectively) and a proportional accumulation of palmitate-enriched
      triacylglycerol species (OPPo, PPPo, and PPP, where Po is palmitoleic acid). We
      conclude that weight cycling changes the ratio of polyunsaturated fatty acids to
      saturated fatty acids and remodels the adipose tissue triacylglycerol species
      profile in rats.

PMID- 9038990
TI  - Purine and pyrimidine nucleotide-sensitive phosphoinositidase C in ampulla from
      frog semicircular canal.
AB  - A microassay was developed to screen the abilities of ATP analogues to stimulate
      phosphoinositidase C in single ventral regions (including dark cells and sensory
      cells) of ampullas microdissected from posterior vertical semicircular canals of
      Rana ridibundo and labeled with myo-[3H]inositol. ATP induced a dose-dependent
      and saturable increase of total [3H]linositol phosphate production accompanied by
      an equivalent decrease in the [3H]phosphoinositide pool. The rank order of
      analogues revealing agonistic potencies for phosphoinositidase C activation was
      as follows: uridine 5'-triphosphate > or = adenosine 5'-O-[3-thiophosphate]
      tetralithium > adenosine 5'-O-[2-thiodiphosphate] trilithium > or = ATP > or =
      ADP = inosine 5'-triphosphate > or = guanosine 5'-triphosphate > or = 2
      methylthio-adenosine 5'-triphosphate tetrasodium > or = 2'-desoxy-thymidine 5'
      triphosphate > or = cytidine 5'-triphosphate = (alpha, beta)-methyl ATP > AMP,
      whereas adenosine 3',5'-cyclic monophosphate and adenosine were almost devoid of
      activity. For antagonists, 1,4'-diisothiocyanostilbene-2, 2'-disulfonic acid was
      far more active than suramin for competitive inhibition of ATP-induced enzyme
      stimulation, whereas reactive blue 2 acted as a noncompetitive inhibitor. Results
      indicate that the putative P2 receptors triggering phosphoinositidase C
      activation in ventral ampullary epithelium from frog semicircular canal exhibit
      mainly the functional properties of P2Y and P2U receptors.

PMID- 9038991
TI  - Gastric distension-induced c-fos expression in catecholaminergic neurons of rat
      dorsal vagal complex.
AB  - Functionally specific vagal afferents were stimulated by gastric balloon
      distension in unanesthetized rats, followed by double c-fos/dopamine beta
      hydroxylase (DBH) immunocytochemistry, to identify second-order neurons in the
      dorsal vagal complex. Continuous and repeated phasic distension with similar
      volumes produced similar numbers and patterns of c-fos expression, with most of
      the activated neurons in the medial and commissural nucleus of the solitary tract
      (NTS) and dorsal motor nucleus (DMNX). Larger distension activated significantly
      more neurons in all responsive areas but there was no differential effect. In
      most NTS subnuclei and the DMNX, a small (3-5%) proportion of gastric distension
      activated neurons was DBH-immunoreactive (DBH-IR), and this proportion did not
      significantly change with type of distension. With continuous and repeated small
      distensions, 10-12% and, with the large distension, 22-30% of all DBH-IR neurons
      expressed c-fos. The results suggest a large degree of convergence between
      rapidly adapting mucosal receptors and slowly adapting tension receptors, but not
      between low- and high-threshold tension receptors, and a relatively minor role of
      catecholaminergic second-order neurons in the dissemination of distension signals
      in the brain.

PMID- 9038992
TI  - Short-day-like body weight changes do not prevent fat pad compensation after
      lipectomy in Siberian hamsters.
AB  - Long-day (LD)-housed Siberian hamsters show compensatory increases in white
      adipose tissue (WAT) weight after lipectomy, whereas hamsters exposed to short
      days (SDs) for a long duration (22 wk) do not. We tested whether SD-induced body
      weight changes prevent fat pad compensation after lipectomy. In experiment 1,
      hamsters with lesions of the paraventricular nucleus of the hypothalamus (PVNx)
      rapidly increased body weight similarly to 22-wk SD-exposed hamsters. In
      experiment 2, LD-housed hamsters were food restricted for 22 wk and then pair fed
      with SD-housed hamsters for 12 wk to produce body weight changes mimicking those
      of ad libitum-fed SD-exposed animals. Epididymal WAT (EWAT) lipectomy (EWATx) of
      PVNx or food-restricted hamsters elicited compensatory increases in
      retroperitoneal and inguinal WAT (RWAT and IWAT) weights. Unlike other fat pads,
      EWAT was less affected by food restriction or PVNx than by SD exposure. In
      general, food restriction decreased adipocyte number, whereas SD exposure
      decreased adipocyte size. PVNx increased RWAT adipocyte size and IWAT adipocyte
      number. These results suggest that the lack of body fat compensation by EWATx
      hamsters exposed to SDs for a long duration is due to SD-associated responses
      other than body weight changes per se.

PMID- 9038993
TI  - Feeding patterns of S. crassicaudata (Marsupialia:Dasyuridae): role of gender,
      photoperiod, and fat stores.
AB  - Little is known about feeding regulation in marsupials. Sminthopsis crassicaudata
      is a small nocturnal marsupial, whose tail contains approximately 25% total body
      fat. We have characterized the effect of gender, photoperiod, food deprivation,
      and tail removal (lipectomy) on food intake in S. crassicaudata. Males and
      females maintained in captivity on long-day (LD, 16:8-h light-dark cycle) and
      short-day (SD, 9:15-h light-dark cycle) light regimens were studied. Feeding
      patterns under LD and SD photoperiods were initially measured under conditions of
      ad libitum food supply and then in groups of animals exposed to 24- and 36-h
      periods of food deprivation. Feeding occurred predominantly in the dark. Females
      maintained on SD photoperiods for 5 wk ate less (P < 0.005) than females on LD or
      males on either SD or LD, but this reduction in food intake was not associated
      with a decrease either in body weight or tail width. After both 24- and 36-h
      fasts, total food intake in the subsequent 24 h increased (P < 0.001) up to 100%
      in all groups, with no gender or photoperiod effect. SD females, however, ate
      less (P < 0.05) than LD females in the first 6 h after refeeding. Tail width
      decreased (P < 0.05) in all groups of animals after the 36-h fast but only in LD
      animals after the 24-h fast (P < 0.05). Body weight decreased similarly in all
      groups of animals after fasting. The effect of tail removal was studied in LD
      males. The procedure, which was well tolerated, resulted in an initial decrease
      in body weight (P < 0.005), which recovered within 3 wk. On day 45 in the animals
      whose tails were removed, body fat was approximately 30% greater than body fat of
      controls (P < 0.02). No significant increase in food intake occurred after tail
      removal. These data demonstrate in Sminthopsis crassicaudata 1) a photoperiod and
      gender-dependent effect on food intake, 2) the ability to regulate the amount and
      distribution of total body fat, and 3) a dissociation between the regulation of
      food intake and changes in body fat stores, which suggest alterations in energy
      expenditure.

PMID- 9038994
TI  - Temperature-dependent shift of pHi in fish white muscle: contributions of passive
      and active processes.
AB  - This study was designed to determine the mechanisms causing temperature-induced
      pH shifts in the white muscle of the marine teleost Zoarces viviparus. The white
      musculature undergoes an intracellular acidification with increasing body
      temperature at a slope of the pH-temperature relationship equal to -0.016 +/-
      0.003 U/degree C. This is in good accordance with the overall relationship
      between the change in pK and the change in temperature of the intracellular
      proteins, which was determined to be -0.013 +/- 0.001 U/degree C. Thus the
      dissociation state of muscle proteins is kept fairly constant in white muscle of
      Zoarces viviparus. The passive component of the observed pH shift, which is due
      to the physicochemical response of the intracellular buffers to temperature
      change, accounts for only 35% of the pH transition. Ventilatory adjustment of
      intracellular PCO2 does not contribute to the temperature-induced shift of
      intracellular pH (pHi) in Zoarces viviparus. Therefore, the remaining 65% of pH
      adjustment must be ascribed to ion exchange mechanisms. The nonbicarbonate buffer
      value amounted to 34.4 +/- 2.3 meq.pH-1 kg cell water-1 at 12 degrees C and
      decreased slightly but not significantly with temperature. On the basis of our
      data we calculated that a removal of 0.52 mmol base equivalents.kg cell water
      1.degree C-1 was necessary to shift pHi to its new steady state.

PMID- 9038995
TI  - The role of menopause in the development of chronic mountain sickness.
AB  - The objective of this study was to investigate the role of menopause in the
      appearance of the physiopathological sequence that leads to chronic mountain
      sickness (CMS) in a high-altitude female population. The females studied are 30
      54 yr old (n = 152) and have permanent residence in Cerro de Pasco (Pasco, Peru;
      4,300 m). The sample was divided into postmenopausal and premenopausal groups for
      comparison. Blood oxygen saturation (SaO2), excessive erythrocytosis [EE,
      measured by the level of hematocrit (Het)], peak expiratory flow rates (PEFR),
      and a score that represents the main signs and symptoms of CMS (CMSscore) were
      measured. Postmenopausal women had higher Het (50.2 +/- 4.04 vs. 47.4 +/- 4.13%,
      P < 0.001), lower SaO2 (81.9 +/- 4.12 vs. 84.7 +/- 3.14%, P < 0.001) and PEFR
      values (489 +/- 101 vs. 534 +/- 90 l/min, P < 0.02), and slightly higher CMSscore
      (19.1 +/- 3.37 vs. 17.9 +/- 3.48, P < 0.06) than premenopausal women. The
      prevalence of women with EE (EE = Hct > 56%) was found to be 8.8%. Forty-five
      percent of the postmenopausal subjects presented a high CMSscore (> 21), whereas
      only 22% of the premenopausal subjects presented this high value (P < 0.02). We
      can therefore conclude that menopause may represent a contributing factor for the
      development of CMS.

PMID- 9038996
TI  - Dissociation of motor activity circadian rhythm in rats after exposure to LD
      cycles of 4-h period.
AB  - For > 30 days Wistar rats were subjected to six dark pulses per day (T4 cycles; 3
      h light, 1 h dark) to study the possibility of dissociating their motor activity
      rhythm into distinct circadian components. Rats of both sexes were used, one-half
      of which were pinealectomized to examine the effect of the pineal gland on the
      entrainment process. Results show that when rats were maintained under T4 a 4-h
      rhythm in their motor activity was present. Rats showed anticipatory activity to
      dark phases, suggesting that the motor activity components are actually entrained
      to the external light/dark (LD) cycles. When rats were left under constant
      darkness after T4, some motor activity components coming from the dark phases
      free ran for several days with different circadian periods. This suggests that
      the motor activity pattern is generated by several circadian oscillators.
      Moreover, the free-running components of motor activity after T4 were more
      evident when T4 was applied after exposure to constant light than after exposure
      to constant darkness. These results support the hypothesis that the circadian
      system of the rat is formed by several circadian oscillators, whose degree of
      coupling depends on light conditions. In constant light, bright light may inhibit
      internal coupling within the system, making it subsequently more susceptible to
      the T4 cycles. No differences were observed between pinealectomized and sham
      operated animals, although females were more sensitive to T4 cycles than males.

PMID- 9038998
TI  - Presence and activity of compounds with GnRH-like activity in the ovary of
      seabream Sparus aurata.
AB  - The binding and activity of gonadotropin-releasing hormone (GnRH) were
      characterized in the mature gilthead seabream (Sparus aurata) ovary by use of an
      analogue of salmon GnRH([D-Arg6,Trp7,Leu8,Pro9-N(Et)]GnRH, sGnRH-A) as labeled
      ligand. The binding of 125I-sGnRH-A to the seabream ovarian membrane preparation
      was saturable, displaceable, reversible, and dependent on time, temperature and
      tissue concentration. Addition of unlabeled s-GnRH-A displaced the radio-ligand
      in a dose-related manner, indicating the presence of one class of high-affinity
      binding sites with an equilibrium dissociation constant of 45.5 +/- 6.2 nM.
      Addition of other GnRH peptides, including salmon GnRH ([Trp7,Leu8]GnRH) and
      chicken GnRH-II ([His5,Trp7,Tyr8]GnRH), also displaced 125I-sGnRH-A; all these
      peptides bound with lower affinities than sGnRH-A to the seabream ovarian binding
      site. In this study, we also demonstrated the presence of compounds with GnRH
      like activity in the ovary of seabream. Seabream ovarian extract stimulated
      pituitary gonadotropin release from the goldfish pituitary and displaced 125I
      sGnRH-A binding in the seabream ovary. Furthermore, addition of sGnRH-A to
      cultured seabream oocytes directly stimulated reinitiation of oocyte meiosis, as
      indicated by germinal vesicle breakdown. Overall, the present study characterizes
      GnRH-binding sites in the seabream ovary and supports the hypothesis that GnRH or
      compounds with GnRH-like activity play an autocrine/paracrine role in the
      regulation of ovarian function in the seabream ovary.

PMID- 9038997
TI  - Effect of hypoxemia on tissue glycogen content and glycolytic enzyme activities
      in fetal sheep.
AB  - We have tested the hypothesis that prolonged fetal hypoxemia causes a reduction
      in glycogenolytic enzyme activities and/or a depletion of fetal glycogen stores.
      We compared the effects of short (4 h) and prolonged (24 h) periods of reduced
      maternal uterine blood flow (RUBF) on glycogen content and on the activities of
      glucose-6-phosphatase (G-6-Pase), glycogen phosphorylase (GPase), and glycogen
      synthase (GSase) in selected fetal tissues. RUBF was reduced in 10 pregnant sheep
      at 135 days of gestation (term approximately 146 days) for either 4 h (n = 5) or
      24 h (n = 5); 5 other fetuses were used as controls. During RUBF, fetal SaC2 was
      decreased from 61.6 +/- 3.9 to 22.0 +/- 1.4% at 4 h and to 26.7 +/- 1.2% at 24 h.
      Hepatic glycogen content was significantly reduced at 4 h of RUBF, but was not
      reduced further at 24 h. Fetal liver GPase (active and total enzyme activity) and
      G-6-Pase activities were reduced at 4 h of RUBF but tended to return toward
      control values at 24 h. Similarly, hepatic GSase activity tended to decrease at 4
      h of RUBF, although the reduction was not quite significant (P = 0.08). We
      conclude that RUBF causes a reduction of fetal glycogen stores and a reduction in
      G-6-Pase and GPase activity at 4 h. Fetal tissue glycogen contents were not
      reduced further at 24 h, compared with 4 h of RUBF, which indicates that fetal
      glycogenolysis is reduced during this time, probably because of the inhibition of
      GPase and G-6-Pase. It is not known why the activities of these enzymes are
      reduced during prolonged RUBF, when circulating epinephrine and norepinephrine
      concentrations are high.

PMID- 9038999
TI  - Food hoarding is increased by pregnancy, lactation, and food deprivation in
      Siberian hamsters.
AB  - Food hoarding by male Siberian hamsters (Phodopus sungorus sungorus) is increased
      only when body mass (fat) is decreased. Pregnancy and lactation result in marked
      decreases in lipid reserves (approximately 50%) in female Siberian hamsters.
      Therefore, the present experiments addressed the following questions: 1) Is food
      hoarding increased after food deprivation in female Siberian hamsters? and 2) How
      do food hoarding and food intake change during pregnancy, lactation, and their
      combination? During measurements in a simulated burrow system food hoarding
      increased after a 32-h fast (approximately 2- to 3-fold) to a level similar to
      that seen previously in males and was markedly increased during pregnancy
      (approximately 12- to 18-fold, lactation, and concurrent pregnancy and lactation
      (approximately 10- to 25-fold for each of the latter 2 conditions). Postfast food
      intake was not different from prefast baseline measures. Food intake was
      increased only during the last few days of pregnancy and was elevated throughout
      lactation. These impressive increases in the level of food hoarding during
      pregnancy, lactation and their combination suggest that food hoarding may play an
      important role in supplying easily accessible energy to subserve these
      reproductive conditions.

PMID- 9039000
TI  - Medullary pathways mediating depressor responses from Na(+)-sensitive sites in
      nucleus of the solitary tract.
AB  - Two series of experiments were done in male Wistar rats to investigate the
      medullary pathways that mediate the depressor responses from sodium-sensitive
      sites in the nucleus of the solitary tract (NTS). In the first series, the
      anterograde tract tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was
      iontophoresed unilaterally at sites in the NTS at which microinjections (20 nl)
      of a 154-175 mM NaCl solution elicited depressor responses. PHA-L injection sites
      were found to be localized within the medial subnucleus of the NTS (Sm). In the
      medulla, PHA-L-labeled fibers and presumptive terminal boutons were observed
      bilaterally, but with an ipsilateral predominance, throughout the rostrocaudal
      extent of the NTS the dorsal motor nucleus of the vagus, area postrema, the
      ventrolateral medulla (VLM), and nucleus ambiguus. The pontine region, containing
      the A5 catecholaminergic cell group and the parabrachial nucleus, also received
      projections from Sm. In the second series of experiments, the effect of blocking
      synaptic transmission in VLM with cobalt chloride (CoCl2; 5 mM, 100 nl) on the
      cardiovascular response elicited by microinjection (20 nl) of hypertonic saline
      (154-175 mM) into the ipsilateral Sm was investigated in the alpha-chloralose
      anesthetized, paralyzed, and artificially ventilated rat. Microinjection of CoCl2
      into VLM, at sites shown in the previous study to receive efferent projections
      from Sm, significantly attenuated the depressor (60%) and bradycardic (80%)
      responses to stimulation of Sm. These data indicate that the sodium-sensitive
      region of the caudal Sm innervates VLM neurons and suggest that these VLM neurons
      are involved in mediating the depressor and bradycardic responses elicited by
      changes in the extracellular concentration of sodium.

PMID- 9039001
TI  - Posttranscriptional mechanisms regulate ontogenic changes in rat renal sodium
      phosphate transporter.
AB  - The present investigation sought to characterize the relationship between
      ontogeny and Na(+)-P(i) transporter expression in the rat kidney. Results showed
      that the maximal reaction rate (nmol.mg protein-1.10 s-1) of Na(+)-P(i) transport
      was highest in 21-day-old rats (2.26 +/- 0.26), was lower in 42- to 45-day-old
      rats (1.44 +/- 0.19) and 4-mo-old rats (0.78 +/- 0.15), and was lowest in 14-day
      old rats (0.50 +/- 0.16) (P = 0.0009, n = 3). The Michaelis constants (mM Pi)
      were not significantly different in the four age groups. Northern blot analysis
      revealed that the abundance of Na(+)-P(i) transporter mRNA was similar in all
      four age groups (n = 5). Western blot analysis demonstrated the highest
      immunoreactive protein signal in the 21-day-old rat (Na(+)-P(i)/beta-actin = 4.15
      +/- 1.16), followed by decreasing protein levels in 42-day-old rats (2.13 +/-
      0.22), 4-mo-old rats (0.85 +/- 0.25), and 14-day-old rats (0.75 +/- 0.37) (P =
      0.022, n = 5). Immunohistochemical analysis of kidney cortex in the four age
      groups showed specific staining of only apical membranes in all samples. We
      conclude that posttranscriptional mechanisms play a role in regulating this
      transporter during rat ontogeny.

PMID- 9039002
TI  - Temporal and spatial expression pattern of the angiotensinogen gene in mice and
      rats.
AB  - In situ hybridization for mouse angiotensinogen (Ao) mRNA was performed using a
      Stu I-Pst I 0.43-kb fragment of exon 2 as a template to synthesize RNA probes.
      The mouse Ao mRNA expression patterns were different from those reported for
      rats. Ao mRNA was expressed in the fetal liver as early as 12.5 days postcoitus,
      and the liver remained the predominant organ of its expression in utero. Within
      the developing kidney, Ao mRNA was demonstrated at 17.5 days postcoitus in the
      proximal straight tubules undergoing loop formation in the medulla. In the
      matured mouse kidney, the expression site is within the outer stripe of outer
      medulla, hence identified as the pars recta, not proximal convoluted tubules.
      Additional studies revealed that, in rats also, Ao mRNA was localized in the pars
      recta. This was in contrast to previously published results that showed that Ao
      mRNA was localized primarily in the proximal convoluted tubules in rats. Thus the
      pars recta appears to be an important intrarenal source of Ao for both rats and
      mice throughout pre- and postnatal periods, whereas the liver can be the major
      extrarenal source in utero in mice, but not in rats.

PMID- 9039003
TI  - Mechanism of attenuated thirst in aging: role of central volume receptors.
AB  - To test the hypothesis that the inhibitory action of central blood volume
      expansion on thirst and renal fluid regulation is attenuated with aging, we
      monitored the drinking and renal responses of dehydrated older (70 +/- 2 yr, n =
      6) and younger (24 +/- 1 yr, n = 6) subjects during 195 min of head-out water
      immersion (HOI), which shifts blood centrally and increases plasma volume (PV).
      Subjects dehydrated by exercising for 2 h at 36 degrees C in the evening and
      refraining from fluids overnight before HOI in 34 degrees C water or a seated
      control in water perfusion suit [time control (TC)] the next morning. Ad libitum
      water intake was allowed after 15 min of HOI. Dehydration decreased PV by 10.6 +/
      1 and 7.3 +/- 1.8% (P < 0.05) and increased plasma osmolality by 6 +/- 2 and 7
      +/- 1 mosmol/kg H2O (P < 0.05) in older and younger subjects, respectively.
      Thirst ratings increased in both groups, but pre-HOI thirst perception on a line
      rating scale was lower in older (69 +/- 8 mm) than younger (94 +/- 6 mm, P <
      0.05) subjects. Fifteen minutes of HOI restored PV by 7.8 +/- 1.0 and 5.7 +/-
      1.0% in older and younger subjects, respectively, but suppressed thirst rating in
      younger subjects only (P < 0.05). Fluid intake was reduced in HOI compared with
      TC in younger (6.3 +/- 0.5 vs. 14.3 +/- 2.2 ml/kg, P < 0.05) but not in older
      (6.7 +/- 2.1 vs. 8.4 +/- 3.3 ml/kg) subjects. During HOI, older subjects had
      smaller suppression of plasma renin activity and aldosterone concentration but a
      greater increase in the plasma atrial natriuretic peptide concentration (P[ANP],
      P < 0.05). HOI increased fractional sodium excretion in both groups, but mean
      arterial pressure increased only in the older subjects (P < 0.05). We conclude
      that the inhibitory influence of central volume expansion on thirst and drinking
      behavior is diminished with aging. Furthermore, in contrast to younger people,
      HOI natriuresis is associated with exaggerated increases in P[ANP] and arterial
      blood pressure in older people, suggesting arterial baroreceptors may be involved
      in the fluid regulatory response to central blood volume expansion in older
      people.

PMID- 9039004
TI  - Corticosterone inhibition of osmotically stimulated vasopressin from hypothalamic
      neurohypophysial explants.
AB  - Glucocorticoids inhibit and glucocorticoid deficiency increases vasopressin (AVP)
      release in vivo. To determine whether the effect of glucocorticoids is
      hypothalamic and mediated via a glucocorticoid receptor, explants of the
      hypothalamic-neurohypophysial system were used to measure AVP release during
      agonist and antagonist exposure. Explants from adult rats, which contained AVP
      neurons of the supraoptic nucleus with axonal projections terminating in the
      neural lobe but excluded the paraventricular nucleus, were perifused with an
      osmotic stimulus (increase of 5 mosmol/h over 6 h) in the absence or presence of
      corticosterone (100 micrograms/dl) or with corticosterone (100 micrograms/dl) in
      the absence or presence of the glucocorticoid antagonist RU-486 (10 microM). AVP
      release was not increased during osmotic stimulation in the presence of
      corticosterone (Cort) and was 20-30% lower than osmotically stimulated release
      observed in the absence of Cort. RU-486 reversed the inhibitory effect of
      corticosterone on AVP release. No changes in AVP mRNA content were detected.
      These results suggest that Cort inhibits osmotically stimulated AVP release by a
      direct effect within the hypothalamus and/or neurohypophysis. This effect is
      mediated by the glucocorticoid receptor through either genomic or nongenomic
      mechanisms.

PMID- 9039005
TI  - Use of [3H]methylglucose and [14C]iodoantipyrine to determine kinetic parameters
      of glucose transport in rat brain.
AB  - Local maximal velocities of transport (Tmax) and the half-maximum transport
      constants (KT) for glucose transport across the blood-brain barrier have been
      determined in local regions of the brain in normal conscious rats.
      [14C]iodoantipyrine and [3H]methylglucose were infused together intravenously for
      2 min in rats with plasma glucose concentrations maintained at different levels,
      and the time courses of the tracer levels in arterial blood were measured. Local
      14C and 3H concentrations were then measured in tissue samples dissected from the
      frozen brains. By comparing the transport-limited uptake of [3H]methylglucose
      with the blood flow-limited uptake of [14C]iodoantipyrine, the value of m, a
      factor between 0 and 10 that accounts for diffusion and/or transport limitations,
      was derived, and from the equation, m = 1 - PS/F (where PS is capillary
      permeability-surface area product and F is cerebral blood flow), the permeability
      capillary surface area for methylglucose was calculated (S. S. Kety. Pharmacol.
      Rev. 3: 1-41, 1951). Values for Tmax and KT for glucose were calculated by
      application of Michaelis-Menten kinetic relationships adapted for the competition
      for transport between glucose and methylglucose. Tmax was determined in three
      representative gray structures and one white structure of the brain: Tmax was 5.3
      +/- 0.3 (SD) mumol.g-1.min-1 in the gray structures and 4.3 mumol.g-1.min-1 in
      the white structure. KT was 3.6 +/- 0.4 (SD) mM in the gray structures and 5.9 mM
      in the white structure. This approach allows the simultaneous determination of
      local values of Tmax and KT for glucose and the rates of blood flow in various
      regions of the brain in conscious animals.

PMID- 9039006
TI  - Eye and gonad: role in the dual-oscillator circadian system of female Japanese
      quail.
AB  - Experiments were conducted to determine the anatomic and physiological basis of
      the dual-oscillator circadian system of female Japanese quail. After blocking of
      ocular light perception by eye-patching, the circadian body temperature rhythm
      dissociates into two circadian components in continuous lighting (LL). One
      component free runs with a period significantly shorter than 24 h [mean period
      (tau) = 22.7 h] and is driven by an ocular pacemaker, whereas the other component
      free runs with a period significantly longer than 24 h (tau = 26.3 h). The long
      free-running rhythm is driven by the same circadian clock that drives the
      circadian rhythm of ovulation. The expression of the long free-running rhythm in
      LL depends on the presence of the ovary: body temperature rhythmicity is
      abolished by ovariectomy. The two free-running oscillators in eye-patched birds
      showed evidence of mutual interaction. Significantly, the phase relationships
      that occur as the two oscillators interact can determine whether or not ovulation
      occurs. The results are discussed in terms of an "internal coincidence" mechanism
      for photoperiodic time measurement.

PMID- 9039007
TI  - Potassium-induced aldosterone secretion involves a Cl(-)-dependent mechanism.
AB  - Stimulation of aldosterone secretion by increases in extracellular potassium
      concentration is associated with increases in the volume of the adrenal
      glomerulosa cell. Because increases in cell volume have been associated with
      increases in aldosterone secretion, the effect of preventing the potassium
      induced increase in cell volume by removal of chloride from the medium on the
      response of dispersed bovine glomerulosa cells grown in primary culture was
      determined. Totally replacing the chloride ion with the methylsulfate ion
      prevented the increase in cell volume and significantly suppressed the increase
      in aldosterone secretion normally associated with increasing [K] to 10 mM. In the
      absence of Cl-, the increase in cytosolic calcium concentration ([Ca2+]c)
      normally induced by increasing the [K] to 10 mM was also significantly
      suppressed. The replacement of 10 mM methylsulfate by Cl- restored the potassium
      induced increase in both cell volume and aldosterone secretion to values not
      different from those found in the presence of 108 mM Cl-. The potassium-induced
      increase in cell volume was dependent also on the presence of extracellular
      calcium. Thus a component of the glomerulosa cell response to an increase in [K]
      may be caused by a chloride-dependent increase in cell volume that is triggered
      by the initial depolarization-induced increase in [Ca2+]c. The increase in cell
      volume enhances the increase in [Ca2+]c and amplifies the increase in aldosterone
      secretion.

PMID- 9039008
TI  - Contribution of energy intake and tissue enzymatic profile to body weight gain in
      high-fat-fed rats.
AB  - The purpose of the current study was to examine the enzymatic profile
      [phosphofructokinase (PFK), beta-hydroxyacyl-CoA dehydrogenase (HADH), and
      citrate synthase (CS)] in gastrocnemius muscle, heart, and liver in rats allowed
      ad libitum access to a high-fat diet (HFD, 45% of kcal from corn oil). Male
      Wistar rats were fed a low-fat diet (LFD, 12% of kcal from corn oil) for a 2-wk
      baseline period after which some continued on the LFD and others were placed on
      the HFD. After 1 wk on the HFD, rats were categorized as obesity-resistant (OR), 
      intermediate (OI), or -prone (OP) on the basis of body weight gain (OR, lower
      tertile; OI, middle tertile; OP, upper tertile). At 1, 2, and 5 wk, rats from
      each group were killed (n = 9-14 from each group/time point) after a 24-h fast.
      At the end of the 5-wk dietary period, weight gain was 114.8 +/- 4.3 in LFD,
      125.2 +/- 3.7 in OR, 147.1 +/- 4.1 in OI, and 173.7 +/- 3.5 g in OP rats (OP > OI
      > OR, LFD; P < 0.001). Energy intake was highly correlated with weight gain on
      the HFD at each time point (r > or = 0.72, P < 0.001). After 1 wk on the HFD,
      significant correlations between the ratio of PFK/HADH (an indication of the
      relative capacity for glycolysis vs. beta-oxidation, r = 0.4, P = 0.03) and
      HADH/CS (an indication of the capacity for beta-oxidation relative to total
      oxidative capacity, r = -0.56, P = 0.001) in the gastrocnemius muscle and weight
      gain were observed. At week 2, significant correlations between these ratios and
      weight gain were observed in the gastrocnemius, liver, and heart. In contrast,
      these ratios were not significantly correlated with weight gain at 5 wk. These
      results suggest that rats most susceptible to weight gain or a HFD are
      characterized by a continuous increase in energy intake (explaining approximately
      50% of the variance in weight gain) and an early tissue enzymatic profile that
      favors carbohydrate over fat use.

PMID- 9039009
TI  - A source of adenosine involved in cardiovascular responses to defense area
      stimulation.
AB  - We have investigated the source of central adenosine important in modulating the
      cardiovascular response to hypothalamic defense area (HDA) stimulation in alpha
      chloralose-anesthetized rats. Microinjections of an ecto-5'-nucleotidase
      inhibitor, alpha,beta-methylene ADP (alpha,beta-meADP), were made into caudal
      nucleus of the solitary tract (cNTS) and rostral ventrolateral medulla (RVLM),
      and its effects on HDA-evoked responses were observed. Stimulation of HDA evoked
      an increase in arterial pressure and a secondary rise in arterial pressure after
      stimulation ceased. There was also an increase in heart rate and hindlimb blood
      flow. alpha,beta-meADP had no effect on resting levels of arterial pressure,
      heart rate, and hindlimb blood flow when injected into the cNTS or RVLM.
      alpha,beta-meADP also had no effect on the HDA-evoked tachycardia and increase in
      muscle blood flow. However, alpha,beta-meADP reduced the primary increase in
      arterial pressure evoked by HDA stimulation when microinjected into the cNTS. In
      contrast, alpha,beta-meADP reduced the secondary increase in arterial pressure
      when microinjected into the RVLM. From these results, we suggest that at least
      part of the adenosine released centrally during HDA stimulation is derived
      extracellularly from ATP metabolism.

PMID- 9039010
TI  - Chronic fetal placental embolization and hypoxemia cause hypertension and
      myocardial hypertrophy in fetal sheep.
AB  - To examine the cardiovascular effects on the fetus of an elevated umbilical
      vascular resistance resulting in fetal hypoxemia, we embolized the fetal side of
      the placenta in pregnant sheep and measured cardiovascular and hormonal changes
      and cellular growth in fetal heart. Chronically catheterized fetal sheep were
      embolized (n = 6) for 21 days between 0.74 and 0.88 of gestation into the
      descending aorta until arterial oxygen content was decreased by 40-50% of the
      preembolization value. Control animals (n = 6) received saline only. During
      embolization, fetuses became chronically hypoxemic (P < 0.001) and hypertensive
      (P < 0.001), with a progressive increase in umbilical artery resistance index (P
      < 0.001). There was also an increase in fetal plasma norepinephrine throughout
      the study period (P < 0.05). On day 21 of embolization, fetuses showed
      asymmetrical growth restriction, increased heart weight (P < 0.01), and increase
      in right and left ventricular wall thickness (P < 0.05) compared with control
      animals. The protein-to-DNA ratio, an index of cell size, increased in the right
      ventricular myocardium in the embolized group (P < 0.001), suggesting myocardial
      cell hypertrophy. We conclude that, during chronic placental damage leading to
      fetal hypoxemia with an increase in umbilical artery resistance index, fetuses
      developed arterial hypertension and asymmetrical growth restriction and that
      increases in afterload to the heart and plasma norepinephrine likely caused fetal
      myocardial hypertrophy.

PMID- 9039011
TI  - Cutaneous vasoconstriction in conscious rabbits during alerting responses
      detected by hippocampal theta-rhythm.
AB  - We determined whether alerting stimuli cause cutaneous vasoconstriction in
      conscious rabbits. We compared ear blood flow with renal, mesenteric, and femoral
      flows at rest and in response to nonnoxious alerting stimuli, which induced theta
      rhythm (4-9 Hz) in the simultaneously recorded hippocampal electroencephalogram
      (EEG). theta-Inducing stimuli (e.g., whistles and fur touches) reduced ear flow
      by 95 +/- 6%, commencing 1-2 s after the EEG change and lasting 45 s. Renal flow
      did not significantly change with alerting stimuli, mesenteric and femoral flows
      slightly decreased, arterial pressure transiently rose (+10 +/- 3 mmHg), and
      heart rate fell (+43 +/- 9 beats/min). At rest, the coefficient of variation for
      ear flow (62 +/- 6%) was greater than for other flows (P < 0.01). Phentolamine (1
      mg/kg iv) reduced this coefficient to 29 +/- 4% (P < 0.01). Our study
      demonstrates that alerting responses in conscious rabbits are associated with
      selective cutaneous vasoconstriction, without increase in flow to skeletal
      muscle.

PMID- 9039012
TI  - H(+)-glycyl-L-proline cotransport in brush-border membrane vesicles of eel
      (Anguilla anguilla) intestine.
AB  - A plasma membrane H(+)-glycyl-L-proline (Gly-L-Pro) cotransport mechanism has
      been identified in isolated eel intestinal brush-border membrane vesicles (BBMV)
      by both measuring radiolabeled Gly-L-Pro uptake and monitoring Gly-L-Pro
      dependent H+ influx with the pH-sensitive dye acridine orange. The application of
      an inside negative membrane potential resulted in increasing Gly-L-Pro uptake, as
      well as the application of inwardly directed H+ gradient (although only when an
      inside negative membrane potential was present). Furthermore, vesicular H+ influx
      was found specifically associated with the presence of Gly-L-Pro in the
      extravesicular medium. The carrier-mediated nature of H(+)-Gly-L-Pro cotransport
      was assessed, and its concentration that yielded one-half maximal Gly-L-Pro
      influx was approximately 1.30 mM when measured by either radioactive or
      fluorescent tracers. Different dipeptides strongly inhibited Gly-L-Pro uptake by
      eel intestinal BBMV, as well as the cephalosporin antibiotic cephalexin,
      suggesting that dipeptide molecules and cephalosporin antibiotics may share a
      common transport system in eel intestinal BBMV.

PMID- 9039013
TI  - Physiological responses to a cold, wet, and windy environment during prolonged
      intermittent walking.
AB  - The potentially deleterious influence of body cooling on the thermoregulatory and
      metabolic responses to prolonged walking exercise has not been established. To
      address this problem, 10 men completed a 6-h intermittent (15 min rest, 45 min
      exercise) walking protocol in a thermoneutral (+15 degrees C) condition (Neutral)
      and a cold (+5 degrees C), wet, and windy condition (Cold). The first two
      exercise periods were conducted at a higher intensity (Higher, 6 km/h and 10%
      incline) than the subsequent four exercise periods (Lower, 5 km/h and 0%
      incline). Rectal temperature was lower and heart rate no different in Cold
      compared with Neutral, whereas the following were higher: oxygen consumption,
      respiratory exchange ratio, plasma norepinephrine and epinephrine, and blood
      lactate and glucose. There was no environmental influence on these variables
      during Higher. In conclusion, heat production during Lower was not sufficient to
      offset heat loss to the cold environment, and the resulting reduction in rectal
      temperature and metabolic perturbations may be detrimental if exercise is
      prolonged.

PMID- 9039015
TI  - Evidence for the anorexia of aging: gastrointestinal transit and hunger in
      healthy elderly vs. young adults.
AB  - Animal studies suggest that aging is associated with anorexia and disordered
      gastrointestinal transit. To determine whether there is a relationship between
      the effects of aging on appetite and gastrointestinal transit in humans, 19 young
      (age 23-50 yr) and 14 elderly (age 70-84 yr) normal volunteers underwent
      measurements of 1) desire to eat, hunger, and fullness (visual analog scales); 2)
      gastric emptying (scintigraphy); 3) orocecal transit (breath hydrogen); 4) total
      gut transit (radiopaque markers); and 5) autonomic nerve function (cardiovascular
      reflexes). We found that, postprandially, elderly subjects had less desire to eat
      (P < 0.05) and less hunger (P < 0.05), but not a significantly greater fullness
      than younger subjects. Gastric emptying (50% emptying time) for solid (182 +/- 26
      vs. 127 +/- 13 min, P < 0.05) and liquid (47 +/- 4 vs. 35 +/- 3 min, P < 0.05)
      meal components was slower in elderly subjects. Postprandial hunger was inversely
      related (r = -0.39, P < 0.05) to solid gastric emptying. There were no
      significant differences in orocecal and total gut transit times between the two
      groups. Autonomic nerve function was abnormal in 11 elderly but none of the young
      subjects (P < 0.01). We conclude that aging is associated with 1) diminished
      desire to eat and hunger, 2) slowing of solid and liquid gastric emptying, 3 no
      change in orocecal and total gut transit, and 4) autonomic nerve dysfunction. The
      slowing of gastric emptying may contribute to anorexia in aging subjects.

PMID- 9039014
TI  - Adrenomedullin-(22-52) antagonizes vasodilator responses to CGRP but not
      adrenomedullin in the cat.
AB  - The effects of adrenomedullin (ADM)-(22-52), a putative ADM receptor antagonist,
      on vasodilator responses to ADM and the structurally related peptide, calcitonin
      gene-related peptide (CGRP), were investigated in the hindlimb vascular bed of
      the cat under constant-flow conditions. ADM-(22-52) had no significant effect on
      hindlimb perfusion pressure when injected in doses up to 120 nmol; after
      administration of ADM-(22-52), vasodilator responses to ADM were unchanged,
      whereas vasodilator responses to CGRP were inhibited. The inhibitory effects of
      ADM-(22-52) on responses to CGRP were selective and reversible and were similar
      to the inhibitory effects of the CGRP antagonist CGRP-(8-37). Hindlimb
      vasodilator responses to CGRP and to ADM were increased in duration by the
      adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor rolipram
      but were not altered by inhibitors of guanosine 3',5'-cyclic monophosphate
      phosphodiesterase, nitric oxide synthetase, K(+)-ATP channels, the cyclooxygenase
      pathway, or the adrenergic nervous system. These results demonstrate that ADM-(22
      52) is a selective CGRP receptor antagonist in the hindlimb vascular bed of the
      cat. The present data suggest that vasodilator responses to CGRP and ADM are
      mediated by different receptors but that these peptides dilate the hindlimb
      vascular bed of the cat by a similar cAMP-dependent mechanism.

PMID- 9039016
TI  - Effect of cholinergic agonists on bulbospinal C1 neurons in rats.
AB  - Cholinergic inputs to the rostral ventrolateral medulla (RVLM) may contribute to
      sympathetic tone generation. The present study analyzes the response of RVLM
      neurons to cholinergic agonists. In chloralose-anesthetized rats iontophoresis of
      carbachol excited RVLM sympathoexcitatory neurons (+69% from resting level of
      11.9 +/- 2 spikes/s; n = 28). This effect was reduced 85% by iontophoresis of
      methylatropine and abolished by intravenous scopolamine. Iontophoresis of
      nicotine or hexamethonium was ineffective. In contrast, most RVLM respiratory
      units were inhibited by carbachol. Whole cell recordings of bulbospinal RVLM
      neurons were made in neonatal rat brain slices (54 cells, 24 C1 adrenergic
      neurons). In current-clamp recordings (without tetrodotoxin) carbachol produced
      depolarization, increased postsynaptic potential frequency, and decreased input
      resistance. In voltage-clamp recording (-50 to -60 mV; 1 microM tetrodotoxin)
      carbachol produced inward current [50% effective concentration (EC50): 10 +/- 1
      microM; 12.6 +/- 2 pA at 30 microM; n = 16] that persisted in low Ca2+/high Mg2+
      (n = 6). Muscarine (30 microM) caused smaller inward currents (2.6 +/- 0.6 pA; n
      = 16). The carbachol-induced current was reduced 46% by 5 microM methylatropine
      (n = 15) and 84% by 200 microM hexamethonium (n = 9). The current was linear as a
      function of the holding potential (extrapolated reversal potential: -22 +/- 2
      mV). In conclusion, carbachol exerts both pre- and postsynaptic effects on C1 and
      other putative sympathoexcitatory RVLM neurons. In vitro the postsynaptic effect
      of carbachol has a mixed nicotinic and muscarinic pharmacology. In vivo,
      iontophoretically applied carbachol produces muscarinic excitation of
      barosensitive RVLM neurons.

PMID- 9039017
TI  - Sexual dysfunction in the diabetic BB/WOR rat: a role of central neuropathy.
AB  - The pathophysiological mechanisms of diabetic impotence remain obscure. We have
      presented an analysis of sexual function in a diabetic rat (BB/WOR) model
      characterized by diffuse neuropathic changes without a confounding vasculopathy
      that allows us to define the neural components of erectile failure. Copulatory
      behavioral testing demonstrated that diabetic males were severely impaired: the
      controls mounted three times more than the diabetics and had about one-half the
      latency to first mount. The diabetics had about one-fourth the number of
      intromissions and took nearly twice as long to achieve first ejaculation. The
      number of ejaculations was drastically reduced as well. We examined sexual
      reflexes in the anesthetized acutely spinalized rat. These experiments tested the
      integrity of spinal circuits controlling sexual function. Reflex testing
      demonstrated that spinal sexual reflexes were also severely impaired: the onset
      latency of reflexes was more than doubled, and the duration of reflexes was less
      than one-half. More than one-half of the diabetic rats showed no penile
      erections. Neural studies showed even more derangement in reflex measures in
      rats, without erection. Nerve conduction velocity experiments suggested a
      peripheral neuropathic change in hypogastric nerve and motor pudendal nerve
      fibers. These dysfunctional findings were seen without any androgen deficiency.
      These results indicate that diabetic impotence in this model reflects central and
      peripheral neuropathic disease processes.

PMID- 9039018
TI  - Regulation of ingestion by CRF and bombesin-like peptides: distinct meal-related
      peptide level changes.
AB  - Bombesin (BN) and corticotropin-releasing factor (CRF) have both been shown to
      induce satiety in rats when injected centrally. The present study assessed
      temporal changes in the utilization of BN- and CRF-like peptides in relationship
      to feeding status, fluctuations that may indicate the physiological participation
      of these peptides in the regulation of feeding. Alterations in the endogenous
      levels of CRF- and BN-like peptides associated with the initial spontaneous meal
      of the nocturnal cycle were determined in 15 hypothalamic and extrahypothalamic
      brain nuclei in the following three groups of rats: 1) a preprandial group
      consisting of rats killed before feeding, 2) a prandial group consisting of rats
      killed during the meal, and 3) a postprandial group consisting of rats killed 8
      12 min after the meal. Findings revealed site-specific changes in BN and CRF
      content during the course of a meal. During ingestion, levels of BN were
      significantly elevated at the paraventricular, arcuate, and dorsomedial nuclei of
      the hypothalamus and reduced at the nucleus accumbens. In the case of CRF,
      feeding-related alterations were observed at the lateral (LH) and ventromedial
      (VMH) hypothalamic nuclei and at the central nucleus of the amygdala (Ce). At the
      LH, CRF content decreased after feeding compared with preprandial levels. At the
      VMH, CRF levels were significantly elevated both before and after food intake
      compared with prandial levels. In contrast, at the Ce marked increases in CRF
      concentrations were observed during ingestion. These data demonstrate, for the
      first time, site-specific fluctuations of BN and CRF in relationship to the
      animal's feeding status and suggest that these peptides may play a role in the
      regulation of food intake.

PMID- 9039019
TI  - Osmoregulation of the magnocellular neuroendocrine system during lactation.
AB  - Glucose utilization and Fos expression were used to compare responses of cerebral
      structures involved in osmoregulation in virgin and lactating rats given 0.15,
      0.85, or 1.5 M NaCl subcutaneously. In virgin animals, glucose utilization
      increased (P < 0.05) in the supraoptic nuclei (SON), paraventricular nuclei
      (PVN), and neural lobe (NL) proportionally to the osmotic stimulus (0.15 M NaCl <
      0.85 M NaCl < 1.5 M NaCl), whereas metabolism in the median preoptic nucleus
      (MPO) and median eminence (ME) increased only after 1.5 M NaCl. In lactating
      rats, enhanced utilization of glucose in response to osmotic stimulation was
      absent in the PVN (0.85 M NaCl), MPO, and ME or significantly (P < 0.01) reduced
      (SON, PVN, NL) compared with virgin animals. Glucose utilization in each
      structure correlated linearly with plasma osmolality but with a lower slope (P <
      0.05) in lactating animals. Magnocellular neurons expressing Fos in the SON
      increased linearly with plasma osmolality and were more numerous (P < 0.05) in
      control lactating animals but increased less (P < 0.05) than in virgin rats after
      0.85 M NaCl. The attenuated magnocellular response during lactation results from
      reduced afferent activation from osmosensitive forebrain sites.

PMID- 9039020
TI  - Stimulation of fluid intake by nutrients: oil is less effective than
      carbohydrate.
AB  - It has been thought that the ability of nutrients to reinforce ingestion is
      related to their ability to provide metabolizable energy. This implies that the
      reinforcing effect of carbohydrate should be similar to that of fat. To test this
      concept, rats were trained in an apparatus that infused water or nutritive
      solutions/suspensions into their stomachs every time they drank a sapid solution.
      Each training trial lasted for 1 day. Successive training trials were
      interspersed by 1-day periods in which the rats were infused with plain water and
      offered plain water or a tastant different from the training taste (i.e., taste
      paired with vehicle infusion). Three different sapid solutions were used: a sweet
      solution (saccharin), a nonsweet solution (NaCl), and a mixture of sweet and
      nonsweet. Starch or maltodextrin infusions strongly and consistently stimulated
      intake of these solutions. Oil infusions also significantly stimulated intake,
      but feebly and less consistently. Indeed, in the one experiment in which the only
      sapid fluid offered was saccharin, oil infusions had no significant effect. Two
      different oil suspensions (one fine and one coarse) were equally ineffective in
      stimulating saccharin intake. To determine whether some unsuspected flaw in the
      infusion experiments somehow produced invalid results, an additional experiment
      was conducted in which rats ingested starch or oil suspensions by mouth.
      Consistent with the infusion experiments, starch stimulated ingestion to a much
      greater degree than did oil. It is concluded that intragastric infusion of
      triglyceride oil is a less potent reinforcer of ingestion than is equicaloric
      infusion of carbohydrate.

PMID- 9039021
TI  - Interleukin-1 beta potentiates bradykinin-induced macromolecular efflux from
      hamster oral mucosa.
AB  - The purpose of this study was to determine whether interleukin-1 beta (IL-1 beta)
      elicits macromolecular efflux from the in situ oral mucosa and whether it
      amplifies that evoked by bradykinin. Using intravital microscopy, we found that
      suffusion of recombinant human IL-1 beta (50 ng/ml) had no significant effects on
      leaky site formation and increase in clearance of fluorescein isothiocyanate
      labeled dextran (mol mass 70 kDa) from the hamster cheek pouch. However, it
      significantly potentiated bradykinin-induced macromolecular efflux (P < 0.05).
      The potentiating effects of IL-1 beta on bradykinin-induced responses were
      abrogated by a bradykinin B2-receptor antagonist and by a recombinant human IL-1
      receptor antagonist. They were not mediated by substance P, prostaglandins, or
      changes in vasomotor tone. IL-1 beta had no significant effects on adenosine
      induced macromolecular efflux. Collectively, these data indicate that IL-1 beta
      potentiates bradykinin-induced macromolecular efflux from the in situ hamster
      oral mucosa in a specific fashion. We suggest that this interaction could play a
      role in the pathogenesis of oral mucosa inflammation.

PMID- 9039022
TI  - NMDA as well as non-NMDA receptors in phrenic nucleus mediate respiratory effects
      of carotid chemoreflex.
AB  - An in vivo model was used to identify the transmitter/receptor mechanisms in the
      phrenic nucleus that mediate carotid chemoreceptor responses. Adult male Wistar
      rats, anesthetized with urethan, were fixed in a stereotaxic instrument, and the
      blood pressure and heart rate were monitored. The rats were immobilized and
      artificially ventilated to maintain the end-tidal CO2 at 4.5-5%. The vagus nerves
      were bilaterally sectioned, and a pneumothorax was produced. Activity was
      recorded from one of the phrenic nerves. The spinal cord was exposed from C1 to
      T1 vertebral level. The dorsal and ventral rootlets of spinal nerves C3, C5, and
      C6, ipsilateral to the phrenic nerve from which electrical activity was recorded,
      were sectioned; the dorsal and ventral roots of spinal nerve C4 were left intact.
      Thus the phrenic nerve bursts recorded in this preparation represented output
      from a portion of the phrenic nucleus located in the ipsilateral C4 spinal
      segment. Carotid chemoreceptor stimulation by N2 inhalation increased the
      amplitude as well as the frequency of phrenic nerve bursts. Microinjections (50
      nl) of a specific N-methyl-d-aspartic acid (NMDA) receptor antagonist (D(-)-2
      amino-7-phosphonoheptanoic acid, AP-7, 50-100 mM) into the phrenic nucleus
      decreased the N2-induced increase in amplitude, but not the frequency, of phrenic
      nerve bursts. Likewise microinjections of a specific non-NMDA receptor antagonist
      (1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulfonamid e, NBQX, 0.5-1
      mM) into the phrenic nucleus decreased the N2-induced increase in phrenic nerve
      burst amplitude. When AP-7 and NBQX were microinjected into the phrenic nucleus
      sequentially within an interval of 5 min, a drastic reduction in the N2-induced
      increase in phrenic nerve burst amplitude was observed. These observations
      suggest that both NMDA and non-NMDA receptors located in the phrenic nucleus are
      involved in the mediation of phrenic nerve responses to the carotid chemoreceptor
      stimulation.

PMID- 9039023
TI  - Involvement of the medial preoptic area in the anorectic action of estrogens.
AB  - The implication of the medial preoptic area (MPOA) as a site for estrogen in the
      regulation of energy balance was investigated. Food intake, O2 consumption (VO2),
      and CO2 production were measured in ovariectomized rats injected with estradiol
      (E2) in the medial preoptic nucleus (MPN). Moreover, knowing the potential for
      corticotropin-releasing factor (CRF) in the anorectic effects of estrogens, we
      identified estrogen receptors (ER) colocalized in CRF-containing cells of the
      MPOA and how MPN injections of CRF compared with estrogen injections with respect
      to VO2 and the VO2-to-CO2 production ratio (respiratory quotient RQ). These
      energy balance measurements after the injections of four different doses of E2 or
      CRF were carried out in meal-fed rats chronically implanted with a guide cannula
      targeted to the MPN. The identification of cells colocalizing ER and CRF was
      determined using a double-immunostaining procedure revealing ER and CRF
      immunoreactivities with two different couplers. The injection of E2 into the MPN
      induced a dose-dependent reduction in food intake, whereas it did not affect VO2
      or RQ. Conversely, the injection of CRF into the MPN had no effect on food intake
      but increased VO2 and decreased RQ. The colocalization of ER and CRF
      immunoreactivities was found in the MPOA and adjacent regions of the bed nucleus
      of the stria terminalis. In conclusion, the results of this study provide
      evidence that the MPOA may represent a potential site for the anorectic effects
      of E2. Furthermore, the presence of ER and CRF in neurons of the MPOA and
      adjacent areas suggests a direct interaction between estrogens and the CRF system
      in the MPOA that is consistent with a role for CRF in the anorectic effects of
      estrogens. Finally, the results of this study indicate that the effects of a CRF
      injection into the MPOA differ from those of estrogens, suggesting that if CRF
      neurons are involved in the anorectic effect of estrogens they likely exert their
      action outside the MPOA.

PMID- 9039025
TI  - Role of extra- and intracellular Ca2+ in the lymphatic myogenic response.
AB  - We used an actively contracting in vitro preparation of bovine mesenteric lymph
      vessels to study the effect of selected calcium channel modulators on the ability
      of these vessels to propel fluid. We found that blocking the dihydropyridine
      receptor with nifedipine and diltiazem inhibited pumping at concentrations within
      the range used clinically (10(-7) and 10(-6) M, respectively). Intracellular
      calcium modulation using ryanodine (10(-6) M) also inhibited pumping.
      Furthermore, we studied the effect of these agents on the relationship between
      lymph flow and transmural pressure, a relationship normally described by a bell
      shaped curve. Diltiazem, 10(-6) M, attenuated pumping over the range of pressures
      studied. On the other hand, ryanodine at 10(-7) M, a concentration capable of
      inhibiting pumping at a constant transmural pressure, had no effect on the
      pressure-flow relationship when transmural pressure was manipulated. Thus we have
      determined that calcium movement via the L-type channel contributes significantly
      to the regulation of lymph pump activity and that intracellular calcium flux
      plays a less significant role that may be modified by transmural pressure.

PMID- 9039024
TI  - Uterine arterial vasoconstrictions mediated by ovarian nerves in virgin and
      postpartum rats.
AB  - In most mammals, including humans, pregnancy results in the loss of most uterine
      vasomotor fibers. These experiments determined whether, despite this denervation,
      sympathetic nerves mediated uterine vasoconstrictions in the rat 24 h after
      delivery. Both virgin and uniparous postpartum rats were anesthetized with
      urethan. Femoral vessels were cannulated for measurement of arterial pressure and
      intravenous administration of fluids and drugs. Blood flow was measured in a
      uterine artery after ligation of all anastomotic ovarian vessels. Electrical
      stimulation of ovarian nerve efferents elicited frequency-dependent uterine
      vasoconstrictions in both virgin and postpartum rats. Vasoconstrictions in
      postpartum rats were not significantly different from those observed in virgins.
      In both virgin and postpartum rats, neurogenic vasoconstrictions were reduced by
      combined alpha 1- and alpha 2-adrenergic blockade. We conclude that the uterine
      branches of the ovarian nerve mediate adrenergic uterine vasoconstrictions. In
      the largely denervated uterus of the postpartum rat, these vasoconstrictions may
      be mediated by surviving innervation of the uterine artery and its major
      branches. Sympathetic vasoconstriction acting at these sites would constitute an
      effective defense against postpartum hemorrhage.

PMID- 9039026
TI  - CCK is involved in both peripheral and central mechanisms controlling food intake
      in chickens.
AB  - The aim of this work was to study the involvement of cholecystokinin (CCK) in the
      control of food intake in chickens. The following aspects were studied: 1) the
      effects of intravenous and intracerebroventricular sulfated octapeptide of CCK
      (CCK-8s) on voluntary food intake; 2) the effects of two CCK-receptor
      antagonists. L-365,260 and L-364,718, on food intake; and 3) the ability of such
      drugs to block the effects of CCK-8s on food intake in the chicken. Intravenous
      and intracerebroventricular CCK-8s caused a decrease in food intake.
      Intraperitoneal L-365,260, a CCK-receptor antagonist with low affinity for the
      two CCK receptors described in the chicken, increases food intake.
      Intracerebroventricular L-364,718, a drug that has high affinity for the chicken
      central CCK-receptor type, increased food intake. The effect of intravenous CCK
      8s on food intake was not blocked by L-364,718 or L-365,260, whereas that of
      intracerebroventricular CCK-8s was blocked by intracerebroventricular L-364,718.
      It is concluded that central endogenous CCK plays a role in the control of food
      intake, which is dependent on central CCK-receptor type; nevertheless, peripheral
      CCK also decreases food intake acting on the peripheral CCK-receptor type. The
      fact that intracerebroventricular L-364,718 is able to increase food intake is
      related to its high affinity for the central CCK-receptor type of this species.
      Finally, three different speculations that might explain the fact that
      intraperitoneal L-365,260 increases food intake are discussed.

PMID- 9039028
TI  - A role for adenosine in metabolic depression in the marine invertebrate
      Sipunculus nudus.
AB  - Involvement of neurotransmitters in metabolic depression under hypoxia and
      hypercapnia was examined in Sipunculus nudus. Concentration changes of several
      putative neurotransmitters in nervous tissue during anoxic or hypercapnic
      exposure or during combined anoxia and hypercapnia were determined. Among amino
      acids (gamma-aminobutyric acid, glutamate, glycine, taurine, serine, and
      aspartate) and monoamines (serotonin, dopamine, and norepinephrine), some changes
      were significant, but none were consistent with metabolic depression under all
      experimental conditions applied. Only the neuromodulator adenosine displayed
      concentration changes in accordance with metabolic depression under all
      experimental conditions. Levels increased during anoxia, during hypercapnia, and
      to an even greater extent during anoxic hypercapnia. Adenosine infusions into
      coelomic fluid via an indwelling catheter induced a significant depression of the
      normocapnic rate of O2 consumption from 0.36 +/- 0.04 to a minimum of 0.24 +/-
      0.02 (SE) mumol.g-1.h-1 after 90 min (n = 6). Application of the adenosine
      antagonist theophylline caused a transient rise in O2 consumption 30 min after
      infusion during hypercapnia but not during normocapnia. Effects of adenosine and
      theophylline were observed in intact individuals but not in isolated body wall
      musculature. The results provide evidence for a role of adenosine in inducing
      metabolic depression in S. nudus, probably through the established effects of
      decreasing neuronal excitability and neurotransmitter release. In consideration
      of our previous finding that metabolic depression in isolated body wall
      musculature was elicited by extracellular acidosis, it is concluded that central
      and cellular mechanisms combine to contribute to the overall reduction in
      metabolic rate in S. nudus.

PMID- 9039027
TI  - Regulation of intracellular pH in avian renal proximal tubules.
AB  - In proximal tubules isolated from chicken transitional nephrons, intracellular pH
      (pHi), measured with the pH-sensitive fluorescent dye 2'.7'-bis(2-carboxyethyl)
      5,6-carboxyfluorescein (BCECF), was approximately 7.3-7.4 under control
      conditions [N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered medium
      with pH 7.4 at 39 degrees C] and was reduced to approximately 6.8 in response to
      NH4Cl pulse. The rate of recovery of pHi (dpHi/dt) from this acid level to the
      resting level and the resting pHi were 1) significantly reduced by the removal of
      Na+ from the bath, 2) significantly increased by the removal of Cl from the bath,
      and 3) unchanged by the removal of both Na+ and Cl from the bath. The addition of
      either amiloride or 4,4'-diisothiocyanostilbene-2,2'-disulfonate to the bath
      reduced dpHi/dt to about the same extent as the removal of Na+. These data
      suggest that both Na(+)-coupled and Cl-coupled acid-base fluxes at the
      basolateral membrane are involved in determining the resting pHi and the rate of
      recovery of pHi after acidification. The most likely possibilities appear to be a
      basolateral Na+/Hi exchanger, a basolateral Na(+)-coupled Cl/HCO3 exchanger, a
      basolateral Na(+)-HCO3(-)CO(3)2 cotransporter, and a basolateral Na(+)
      independent Cl-/HCO3 exchanger.

PMID- 9039029
TI  - Carbohydrate versus fat intake: differing patterns of macronutrient selection in
      two inbred mouse strains.
AB  - As a first step toward developing a mouse model to characterize genetic factors
      linked to the preferential intake of dietary carbohydrate or fat, we have
      identified two mouse strains that exhibit distinctly different patterns of
      macronutrient selection. Macronutrient selection was evaluated in AKR/J and SWR/J
      mice, two strains that have been characterized previously for their sensitivity
      to high-fat dietary obesity. Mice were adapted to a self-selection protocol in
      which separate carbohydrate, fat, and protein sources were simultaneously
      available. AKR/J mice ate 30% more calories than the SWR/J mice. Furthermore,
      strain comparisons revealed a significantly higher proportion of fat intake by
      the AKR/J mice (69 vs. 28%), and in the SWR/J mice a significantly higher intake
      of carbohydrate (62 vs. 24%). The mice were then returned to a standard chow diet
      for 10 wk. These mice subsequently were allowed to self-select from two composite
      energy diets (carbohydrate and protein, or fat and protein). Once again, AKR/J
      mice selected a greater proportion of energy from the fat/protein diet (85%) than
      did the SWR/J strain (32%). These findings suggest a possible relationship
      between sensitivity to dietary obesity and fat selection.

PMID- 9039030
TI  - Adaptations of glutathione antioxidant system to endurance training are tissue
      and muscle fiber specific.
AB  - The effect of endurance training on glutathione (GSH) status and antioxidant
      enzyme system was investigated in skeletal muscle, heart, and liver of female
      Sprague-Dawley rats pair fed an isocaloric diet. Ten weeks of treadmill training
      (25 m/min, 10% grade for 2 h/day, 5 days/wk) increased citrate synthase activity
      in the deep vastus lateralis (DVL) and soleus muscles by 79 and 39%, respectively
      (P < 0.01), but not in the heart or liver. In DVL, GSH content was increased 33%
      (P < 0.05) with training, accompanied by a 64% (P < 0.05) increase in glutamate
      content but no change in cysteine. Trained rats showed a 62 and 27% higher GSH
      peroxidase (GPX) and superoxide dismutase (SOD) activity, respectively (P <
      0.05), in DVL compared with control rats. In contrast, GSH content and
      glutathione reductase (GR) activity in soleus declined with training (P < 0.05),
      whereas activities of GPX and SOD remained unchanged. Training did not alter GSH
      status in the liver or plasma but significantly decreased the GSH-to glutathione
      disulfide ratio in the heart. In addition, GR activity in the liver and GSH
      sulfur-transferase activity in the heart and DVL were significantly lower in the
      trained vs control rats DVL muscle had threefold higher gamma-glutamyl
      transpeptidase activity compared with other tissues; however no significant
      alteration was observed in the activity of gamma-glutamyltranspeptidase or gamma
      glutamylcysteine synthetase in the liver, heart, or skeletal muscle. These data
      indicate that endurance training can cause tissue- and muscle fiber-specific
      adaptation of antioxidant systems and that GSH homeostasis in extrahepatic
      tissues may be determined by utilization and uptake of GSH via the gamma-glutamyl
      cycle.

PMID- 9039031
TI  - Sex differences in the cardiovascular and renal actions of vasopressin in
      conscious rats.
AB  - The present study was carried out to investigate whether prostaglandins (PG) are
      involved in the mechanism that contributes to the sex difference in the
      antidiuretic and pressor actions of vasopressin. The experiments were performed
      in conscious male and nonestrous female rats. In hydrated rats, the graded
      infusion of vasopressin (10-1,000 pg.min 1.kg body wt-1) resulted in a dose
      dependent antidiuresis: decreases in urine flow and free water clearance and an
      increase in urine osmolality. These responses were significantly greater in male
      than in nonestrous female rats. Pretreatment with a cyclooxygenase inhibitor,
      indomethacin (10 mg/kg body wt iv), significantly enhanced the antidiuretic
      response to vasopressin in both sexes. However, the magnitude of this enhancement
      was greater in female than in male rats. Thus indomethacin abolished the sex
      difference in the antidiuretic response to vasopressin. In a separate experiment
      in rats without water hydration and urine collection, infusion of pressor doses
      of vasopressin (1,000-6,000 pg.min-1.kg body wt-1) resulted in a greater increase
      in blood pressure in male than in nonestrous female rats. Treatment with
      indomethacin enhanced this response equivalently in both sexes and thus did not
      affect the sex difference in the pressor action of vasopressin. These data
      indicate that renal PG may mediate, at least in part, the sex difference in the
      antidiuretic action of vasopressin, whereas vascular PG seem not to play an
      important role in the sex difference in the pressor action of vasopressin.

PMID- 9039032
TI  - Effects of progesterone on blood pressure, plasma volume, and responses to
      hypotension.
AB  - Gonadal steroids have been implicated in the control of blood pressure and fluid
      homeostasis. These experiments test the effect of progesterone in ovariectomized
      ewes on blood pressure, volume, and hormone responses to hypotension. Eight ewes
      were each studied in four conditions: ovariectomized, progesterone and estrogen
      replaced, progesterone replaced, or sham treated. During each treatment mean
      arterial pressure (MAP), plasma volume (PV), baroreflex responsiveness, and
      adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), and renin
      responses to hypotension were determined. Progesterone treatment significantly
      reduced resting MAP and increased PV compared with ovariectomy or sham
      treatments. Heart period at 85 mmHg was reduced with progesterone treatment.
      There was no effect of progesterone treatment on ACTH, AVP, or renin or heart
      rate responses to hypotension. Basal AVP levels were increased, and angiotensin
      II concentrations were decreased, by estrogen and progesterone and by sham
      treatments; plasma Na+ also tended to be increased during these treatments. These
      results suggest that a small increase in progesterone can reset resting MAP and
      PV without altering reflex heart rate or endocrine responses to hypotension.

PMID- 9039033
TI  - Is active skeletal muscle functionally vasoconstricted during dynamic exercise in
      conscious dogs?
AB  - We investigated whether the increase in hindlimb blood flow and vascular
      conductance in conscious dogs during graded dynamic exercise is functionally
      restrained by the sympathetic nervous system. Dogs were chronically instrumented
      to monitor terminal aortic blood flow (TAQ) as an index of hindlimb skeletal
      muscle blood flow and mean arterial pressure (MAP). The extent of functional
      sympathetic tone was assessed by measuring the increase in TAQ and terminal
      aortic vascular conductance (TAC, calculated as TAQ/MAP) in response to intra
      arterial infusion of the alpha-adrenergic antagonist prazosin (PZ; 50
      micrograms/kg) into the hind-limbs at rest and during steady-state dynamic
      (treadmill) exercise ranging from mild (3.2 km/h, 0% grade to moderately heavy (8
      km/h, 15% grade) workloads. This dose of PZ completely abolished the large
      hindlimb vasoconstrictor response to phenylephrine (1 microgram/kg ia). At rest,
      PZ increased TAQ by 0.10 +/- 0.02 l/min and TAC by 1.85 +/- 0.53 ml.min-1.mmHg-1.
      During exercise, as workload increased and the control levels of TAQ and TAC rose
      progressively delta TAQ and delta TAC with PZ infusion also increased. At the
      highest workload, PZ increased TAQ by 0.41 +/- 0.07 l/min and TAC by 4.81 +/-
      0.38 ml.min-1.mmHg-1. The increase in TAQ and TAC with PZ were linearly related
      to the control level of TAQ, indicating that as workload increases progressively
      greater restraint of muscle vasodilation by the sympathetic nervous system
      occurs. We conclude that during dynamic exercise in conscious dogs the
      sympathetic nervous system progressively restrains the normal vasodilation in
      active skeletal muscle, thereby limiting skeletal muscle perfusion.

PMID- 9039034
TI  - Pituitary and adrenals are required for hyperglycemic reflex initiated by
      stimulation of CBR with cyanide.
AB  - We have previously shown that stimulation of carotid body receptors (CBR) with
      sodium cyanide (NaCN) elicits a rapid hyperglycemic reflex. Here we explore
      whether the pituitary and adrenals, two glands involved in glucose homeostasis,
      are necessary for this reflex. Experiments were performed on anesthetized rats
      that were artificially ventilated. Measurements of hepatic venous-arterial
      glucose difference indicated that CBR stimulation with a bolus of 5
      micrograms/100 g NaCN produced an immediate increase in the output of glucose by
      the liver. The same dose of NaCN failed to increase hepatic output of glucose in
      rats with bilateral adrenalectomy or in rats 1 wk after surgical removal of
      neurohypophysis. Reflex glucose output by the liver was maintained after
      adenohypophysectomy or in adrenalectomized rats after adrenal autotransplantation
      to epiploon. Measurements of epinephrine in plasma and in the grafted adrenal
      tissue showed that the adrenal autograft can store and secrete catecholamines
      Immunocytochemical observations indicated that the grafted adrenals retain
      medullary cells. These results indicate that neurohypophysis and adrenals are
      necessary for the hyperglycemic reflex initiated by CBR stimulation with NaCN and
      that the participation of these two organs in this reflex is probably humoral.

PMID- 9039035
TI  - Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. I.
      Lipoprivation.
AB  - Metabolic energy availability has profound effects on reproduction in a wide
      variety of species. We have been studying the effects of fasting on estrous
      cycles in Syrian hamsters as a model system for metabolic control of
      reproduction. In previous experiments, a 48-h period of fasting inhibited estrous
      cycles in lean, but not fat, hamsters. In fat hamsters the effects of fasting may
      have been offset by the presence of high circulating levels of free fatty acids
      mobilized from lipids in adipose tissue. Consistent with this idea fat hamsters
      treated with the inhibitor of fatty acid oxidation methyl palmoxirate (MP) showed
      fasting-induced anestrus. Experiment 1 was designed to examine whether vagally
      transmitted signals are critical for the inhibitory effects of fasting and MP
      treatment. Lean or fat hamsters that had received bilateral subdiaphragmatic
      vagotomy or sham surgery were fasted and treated with MP or vehicle. In
      vagotomized and sham-operated hamsters, estrous cycles were inhibited in lean
      fasted hamsters and in fat fasted hamsters treated with MP, but not in fat fasted
      hamsters treated with vehicle. Thus the results of experiment 1 indicated that
      vagally transmitted signals about peripheral fatty acid availability are not
      critical for the effects of these particular metabolic challenges on estrous
      cycles in Syrian hamsters. In experiment 2, hamsters without food were allowed to
      ingest pure glucose or fructose solutions or vegetable shortening. One-half of
      each group was treated with an inhibitor of glucose utilization, 2-deoxy-D
      glucose (2-DG), or vehicle. If ingestion of fructose or shortening, but not
      glucose, had protected hamsters from 2-DG-induced anestrus, this might have
      indicated that peripheral fuel availability is critical for anestrus. On the
      contrary, 2-DG treatment induced anestrus regardless of the type of fuel
      ingested. Neither experiment yielded results that implicated changes in
      peripheral fuel availability as a critical signal in metabolic control of estrous
      cycles.

PMID- 9039036
TI  - Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters.
      II. Glucoprivation.
AB  - Estrous cycles in Syrian hamsters are inhibited by food deprivation or treatment
      with pharmacological inhibitors of intracellular glucose utilization (glucoprivic
      treatments). These same metabolic challenges increase neural stimulation in areas
      of the caudal brain stem thought to be involved in detection of metabolic
      signals. Experiment 1 was designed to examine whether vagally transmitted signals
      are important for glucoprivic effects on estrous cycles and on neural stimulation
      in the caudal brain stem. Vagotomized or sham-operated hamsters were treated with
      2-deoxy-D-glucose (2-DG) at a dose known to decrease cellular glucose utilization
      and inhibit estrous cycles (1,750 mg/kg). Vagotomized and sham-operated hamsters
      did not differ significantly in incidence of 2-DG-induced anestrus or in neural
      stimulation in the caudal brain stem, but the effects of 2-DG on estrous cycles
      and neural stimulation appeared to have been attenuated in vagotomized hamsters.
      In experiment 2, hamsters were injected intracerebroventricularly with 2-DG or
      glucose at doses that did not induce anestrus when injected systemically (125 and
      250 mg/kg). Groups treated with intracerebroventricular injections of 2-DG showed
      a significantly higher incidence of anestrus than those treated with glucose. In
      experiment 3, effects of systemic injections of 2-DG were prevented by prior
      injection of glucose or fructose at the same concentration, indicating that 2-DG
      acts via effects on glucose metabolism, rather than via a nonspecific
      pharmacological effect or generalized stress response. Results of these
      experiments and those reported elsewhere (J. E. Schneider, A. J. Hall, and G. N.
      Wade. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol, 41) R400-R405,
      1997] are consistent with the notion that central glucoprivation is sufficient,
      whereas peripheral lipoprivation is not critical, for metabolic effects on
      estrous cycles.

PMID- 9039037
TI  - Neurophysiological modeling of voiding in rats: bladder pressure and
      postganglionic bladder nerve activity.
AB  - A model was developed that describes the relations between bladder pressure and
      both efferent and afferent nerve activity in postganglionic bladder nerves in
      urethan-anesthetized rats. Nerve activity was calculated as the 100-ms time
      integral of the rectified nerve signal. Afferent and efferent nerve signals were
      measured separately by crushing the nerve proximally or distally. A linear
      relation was found between bladder pressure and afferent nerve activity (fit
      error < 7%), and the relation between bladder pressure and efferent nerve
      activity was described by a low-pass filter (fit error < 90%). In most
      experiments, combined (efferent and afferent) nerve activity was measured.
      Absence of efferent nerve activity was assumed during the pressure decrease
      immediately after voiding. From this episode, the afferent nerve activity was
      estimated for the entire measurement. Efferent nerve activity was then estimated
      assuming linear addition in the bidirectionally conducting nerves. The model
      described the measured data very well (fit error < 7%), and the model parameters
      showed a good reproducibility in each rat (SD was approximately 30% of the mean).

PMID- 9039038
TI  - Transplantation of fetal suprachiasmatic nuclei into middle-aged rats restores
      diurnal Fos expression in host.
AB  - In young animals, the suprachiasmatic nuclei (SCN) of the hypothalamus, which are
      critical circadian pacemakers, exhibit a light-induced diurnal rhythm in Fos
      expression. The expression of this immediate-early gene has been used as an index
      of the activity of the SCN and their ability to respond to external cues that
      entrain them, such as light. In the present study, we show that by the time rats
      reach middle age baseline Fos expression increases prematurely during the dark
      and that light-induced Fos expression is blunted and delayed. We also demonstrate
      that transplantation of fetal tissue containing the SCN into the third cerebral
      ventricle of middle-aged rats enables aged hosts to regain the ability to exhibit
      diurnal patterns of Fos expression that are strikingly similar to those observed
      in young animals. Our findings lead to the following conclusions: 1) the diurnal
      pattern of activity of SCN cells is blunted in middle-aged rats, and 2) SCN
      transplants provide unique signals that enable the cellular systems of the host
      to regain rhythmic functional capabilities. These results provide new insights
      into the critical active role that the host plays in restoration of function
      evoked by the presence of a transplant.

PMID- 9039039
TI  - GLUT-4 protein and citrate synthase activity in distally or proximally denervated
      rat soleus muscle.
AB  - The potential role of neurotrophic factors in the decline of glucose transporter
      (GLUT-4) protein levels and citrate synthase (CS) activity was studied by
      comparing distally with proximally denervated juvenile rat soleus muscle.
      Severing of the tibial nerve produced distal (long stump) or proximal (short
      stump) denervation. GLUT-4 levels and CS activities were measured at 24-h
      intervals for up to 96 h after denervation. No differences were observed in GLUT
      4 or CS activity between soleus muscles left with short or long nerve stumps at
      any time point. However, within just 24 h, denervation decreased (P < 0.05). GLUT
      4 and CS (67.4 +/- 3.3 and 63.4 +/- 1.7% of innervated control values,
      respectively). Both parameters continued to decline up to 96 h (44.4 +/- 3.1 and
      48.7 +/- 4.0%, respectively). There was a significant correlation between the
      GLUT-4 protein level and CS activity over this 96-h period of denervation (r =
      0.653, P < 0.001). A similar response in the 24-h denervated soleus of adult rats
      was observed. In contrast, 24-h denervation of red gastrocnemius (type IIa
      fibers) left with a long nerve stump resulted in a prevention of the decline of
      GLUT-4 and CS seen in red gastrocnemius left with a short nerve stump in both
      juvenile and adult animals. These results suggest that unlike type IIa muscles,
      the decline in GLUT-4 level and CS activity in type I soleus muscle after
      denervation results from a lack of coordinated electrical activity but likely
      does not involve a neurotrophic agent. These results also support the hypothesis
      that there is coregulation of decreased expression of GLUT-4 protein and CS
      activity in this model of reduced neuromuscular activity.

PMID- 9039041
TI  - The non-steady state of pregnancy.

PMID- 9039040
TI  - Caudal hindbrain neuromedin B-preferring receptors participate in the control of
      food intake.
AB  - Recent studies have identified two subtypes of bombesin (BN) receptors in the rat
      central nervous system: gastrin releasing-peptide (GRP) preferring and neuromedin
      B (NMB) preferring. To investigate a role for the NMB-preferring receptor subtype
      in feeding suppression elicited by fourth ventricular (4V) BN administration, we
      evaluated the ability of a selective NMB-preferring receptor antagonist, BIM
      23127, to block suppression of glucose intake produced by 4V BN (10 pmol). Our
      results showed that 4V administration of BIM-23127 dose dependently antagonized
      the suppression of glucose intake produced by 4V BN. In addition, 4V
      administration of BIM-23127 alone increased glucose intake above that observed in
      the baseline condition. These results support a role for the NMB-preferring BN
      receptor subtype in the suppression of intake produced by 4V BN administration
      and suggest that endogenously released NMB participates in ingestive control.

PMID- 9039042
TI  - What's in a name?

PMID- 9039043
TI  - Molecular physiology of urinary concentrating mechanism: regulation of aquaporin
      water channels by vasopressin.
AB  - The purpose of this review is to illustrate the application of molecular
      methodologies to the investigation of a fundamentally integrative problem in
      renal physiology, namely, the mechanism of regulation of water excretion by the
      kidney and the concomitant concentration of solutes in the urine. A new
      revolution in renal physiology is occurring as new research tools have become
      available as a result of the cloning of cDNAs for many of the major transporters
      and receptors in the renal medulla. Among the important renal medullary
      transporters are the aquaporin water channels, which mediate the osmotic water
      transport across renal medullary epithelia. One of these water channels,
      aquaporin-2, has been shown to be the target for short-term regulation of
      collecting duct water permeability by vasopressin. In addition, two collecting
      duct water channels, aquaporin-2 and aquaporin-3, are targets for long-term
      regulation by vasopressin through effects on the absolute expression levels of
      the water channel proteins. This review focuses on the mechanisms of both short-
      and long-term regulation of these water channels by vasopressin.

PMID- 9039044
TI  - Amylin stimulates proximal tubular sodium transport and cell proliferation in the
      rat kidney.
AB  - In autoradiographic studies in anesthetized rats, 125I-labeled amylin binding was
      associated with proximal convoluted tubules but not distal tubules, interstitium,
      or glomeruli in the renal cortex. Split-drop micropuncture experiments showed
      that perfusion of the peritubular capillaries with amylin (10(-9) M) stimulated
      proximal tubular fluid absorption by 28%. This effect was inhibited by luminal
      addition of ethylisopropylamiloride, indicating mediation by a brush-border
      Na+/H+ exchanger. Intravenous infusion of an amylin binding antagonist, AC-187,
      reduced proximal fluid reabsorption (22%) in anesthetized rats, indicating a role
      for endogenous amylin in salt homeostasis. In primary cultures of rat proximal
      tubule cells, amylin (10(-7) M) stimulated proliferation with a potency equal to
      epidermal growth factor. Peptide antagonists (AC-187, AC-413, and AC-512) of the
      amylin binding sites in the renal cortex blocked the mitogenic action of amylin.
      We conclude that amylin acts on renal proximal tubules to promote sodium and
      water reabsorption and cell proliferation. These novel actions may have
      implications for the development of hypertension for example in non-insulin
      dependent diabetes mellitus and obesity in which hyperamylinemia has been
      observed.

PMID- 9039045
TI  - Effect of chronic hypokalemia on H(+)-K(+)-ATPase expression in rat colon.
AB  - Although the kidney plays the major role in the regulation of systemic K+
      homeostasis, the colon also participates substantively in K+ balance. The colon
      is capable of both K+ absorption and secretion, the magnitude of which can be
      modulated in response to dietary K+ intake. The H(+)-K(+)-adenosinetriphosphatase
      (H(+)-K(+)-ATPase) has been proposed as a possible mediator of K+ absorption in
      distal colon, but inhibitor profiles obtained in recent studies suggest that two,
      and perhaps more, distinct H(+)-K(+)-ATPase activities may be present in
      mammalian distal colon. We have developed highly specific probes for the
      catalytic alpha-subunits of colonic and gastric H(+)-K(+)-ATPase, alpha 1-Na(+)
      K(+)-ATPase, and beta-actin, which were used in Northern analysis of total RNA
      from whole distal colon and stomach obtained from one of three experimental
      groups of rats: 1) controls, 2) chronic dietary K+ depletion, and 3) chronic
      metabolic acidosis. The probe for the colonic but not the gastric H(+)-K(+)
      ATPase alpha-isoform hybridized to distal colon total RNA in all groups. A
      significant increase in colonic H(+)-K(+)-ATPase mRNA abundance was observed in
      response to chronic dietary K+ depletion but not to chronic metabolic acidosis.
      The alpha 1-isoform of Na(+)-K(+)-ATPase, which is also expressed in distal
      colon, did not respond consistently to either chronic dietary K+ depletion or
      chronic metabolic acidosis. The gastric probe did not hybridize to total RNA from
      distal colon but, as expected, hybridized to total stomach RNA. However, the
      abundance of gastric H(+)-K(+)-ATPase or Na(+)-K(+)-ATPase in stomach was not
      altered consistently by either chronic dietary K+ depletion or metabolic
      acidosis. Under the conditions of this study, it appears that the mRNA encoding
      the colonic alpha-isoform is upregulated by chronic dietary K+ restriction, a
      condition shown previously to increase K+ absorption in the distal colon.

PMID- 9039046
TI  - Endothelin increases NO-dependent cGMP production in isolated glomeruli but not
      in mesangial cells.
AB  - The ability of endothelins (ETs) to modulate nitric oxide-dependent glomerular
      guanosine 3'-5'-cyclic monophosphate (cGMP) production has recently been
      reported. The aim of this study was to directly confirm, using an antagonist, the
      involvement of the ETB receptor subtype and to investigate the potential role of
      mesangial cells (MC) in this ET-induced cGMP production. In glomeruli freshly
      isolated from rats, endothelin-3 (ET-3) induced a dose-dependent increase in cGMP
      content. This increase was inhibited by NG-monomethyl-L-arginine (L-NMMA) and
      methylene blue and was calcium dependent. Moreover, the effect of ET-3 was
      prevented by two ETB-selective receptor antagonists, BQ-788 and IRL-1038, but not
      by BQ-123, an ETA-selective receptor antagonist. It therefore appeared that ET-3
      stimulates the glomerular constitutive NO pathway through activation of the ETB
      receptor subtype. In contrast, ET-3 and calcium ionophore had no effect on cGMP
      formation in cultured MC, whereas incubation with sodium nitroprusside resulted
      in an approximately 50-fold increase in the intracellular content of cGMP.
      However, ET-3 induced a dose-dependent rise in free MC cytosolic calcium that was
      abolished by an ETB antagonist. Moreover, both ETA and ETB receptors mRNA were
      expressed in primary cultures of MC. Finally, we failed to detect the presence of
      constitutive NO synthase (NOS), as demonstrated by the absence of L-citrulline
      forming activity and of the mRNA encoding for endothelial NOS, whereas they were
      present in isolated glomeruli. These data indicate that MC, despite the fact that
      they express ETB receptors, are not involved in glomerular NO production induced
      by exposure to ET-3, because they do not express constitutive NO synthase.

PMID- 9039047
TI  - Arginine vasopressin interacts with thromboxane in hydronephrosis.
AB  - The influence of hydronephrosis (6-10 wk) on the renal vascular response to
      arginine vasopressin (AVP) was assessed, using isolated perfused normal and
      hydronephrotic rat kidneys. In normal kidneys, AVP (0.3 nM) reduced renal
      perfusate flow (RPF) by 55 +/- 7% (P < 0.01). AVP-induced decrements in RPF were
      reversed partially by diltiazem (10 microM) and completely by 10 nM of an AVP
      (V1)-receptor antagonist (AVPX). In hydronephrotic kidneys, AVP reduced RPF by 81
      +/- 2% (P < 0.01) and constricted afferent (AA) and efferent arterioles (EA) by
      33 +/- 3 (P < 0.01) and 33 +/- 5% (P < 0.01), respectively. The addition of
      diltiazem altered neither RPF nor vessel diameters. Administration of AVPX
      recovered RPF, AA, and EA diameters. When hydronephrotic kidneys were pretreated
      with thromboxane (Tx) inhibitors, AVP reduced RPF by 62 +/- 5% (P < 0.01) and
      constricted AAs and EAs by 26 +/- 2 (P < 0.01) and 17 +/- 3% (P < 0.05),
      respectively. Under Tx blockade, diltiazem partially reversed the AVP-induced
      reduction in RPF and restored the decrements in AA diameter. Subsequent addition
      of AVPX returned RPF and EA diameter. Our data indicate that AVP elicits
      substantial renal microvascular constriction and suggest that AVP stimulates Tx
      production in hydronephrotic kidneys, thereby altering renal vascular
      responsiveness to this peptide.

PMID- 9039048
TI  - Nitric oxide prevents neutrophil-mediated acute renal failure.
AB  - The contribution of nitric oxide (NO) to ischemic acute renal failure is unclear.
      Because polymorphonuclear neutrophils (PMN) accentuate injury in kidneys
      subjected to ischemia-reperfusion and because NO has potent vascular and PMN
      effects, we examined the contribution of NO to PMN-mediated injury in isolated
      perfused rat kidneys. Nonischemic and ischemic kidneys were perfused by the
      isolated kidney technique in the presence or absence of PMN and NO agonists
      [sodium nitroprusside (SNP), L-arginine (L-Arg)] or a NO synthase inhibitor [N
      omega-nitro-L-arginine (L-NNA)]. In nonischemic kidneys, the NOS antagonist
      decreased perfusion flow rate by 25% without affecting glomerular filtration rate
      (GFR) or tubular sodium reabsorption (TNa), whereas NOS agonist treatment had no
      effects. After 20 min of ischemia/60 min reperfusion in the absence of PMN NO
      agonist treatment potentiated ischemia-reperfusion-induced loss of GFR and TNa,
      whereas adding the NO antagonist lessened glomerular and tubular injury.
      Reperfusion of ischemic kidneys with PMN resulted in PMN retention and
      potentiated ischemic injury. However, increases in PMN retention as well as
      decreases in GFR and TNa caused by PMN were prevented by SNP and worsened by L
      NNA. Moreover, in nonischemic kidneys, activated PMN caused renal injury and PMN
      retention, which were prevented by SNP and worsened by L-NNA. In conclusion, 1)
      NO worsens ischemic injury in the absence of PMN, and 2) NO prevents the PMN
      component of ischemic renal injury by blocking PMN retention and the deleterious
      effects of activated PMN on glomerular and tubular function.

PMID- 9039049
TI  - Surface exposure of phosphatidylserine increases calcium oxalate crystal
      attachment to IMCD cells.
AB  - The development of urolithiasis is a multifaceted process, starting at urine
      supersaturation and ending with the formation of mature renal calculi. The
      retention of microcrystals by the urothelial cell membrane is a critical event in
      the process. The current study examines calcium oxalate monohydrate (COM) crystal
      attachment to inner medullary collecting duct (IMCD) cells following selective
      changes in cell membrane phospholipid composition. Both primary culture of IMCD
      cells and a continuous IMCD cell line were used for these studies. Cell membrane
      composition was selectively altered by either exogenous addition of membrane
      phospholipids or using membrane lipid scrambling agents. Enrichment with anionic
      phospholipids was found to greatly increase attachment of crystals to the cells.
      This increased attachment correlated with the exposure of phosphatidylserine (PS)
      on the exofacial leaflet of the cell membrane as demonstrated by the use of the
      membrane scrambling agent A-23187. Furthermore, the increased COM attachment
      following PS exposure could be blocked by incubating the cells with the PS
      specific binding protein, annexin V. These results support the hypothesis that
      exposure of PS head groups on the papillary epithelial cell surface may mediate
      stone crystal attachment to the kidney tubule cell epithelium in the renal
      papilla, possibly as an initiating event in urolithiasis.

PMID- 9039050
TI  - Altered organic anion and osmolyte content and excretion in rat polycystic kidney
      disease: an NMR study.
AB  - Polycystic kidney disease (PKD) is the fourth most common cause of end-stage
      renal disease and the most common potentially lethal inherited disease in humans.
      Early identification of carriers of dominant PKD in the absence of genetic
      markers is problematic in both humans and the Han:SPRD-cy/+ rat, a model of PKD
      that shares many features of human disease. We undertook a proton magnetic
      resonance imaging (MRI) study of young Han:SPRD-cy/+ and unaffected Han:SPRD(
      )+/+ animals to determine whether carrier status could be identified based upon
      image appearance or signal characteristics. Affected animals demonstrated
      significant prolongation of longitudinal relaxation time (T1) and transverse
      relaxation time (T2) in both cystic renal cortex and noncystic renal medulla.
      Both of these measurements correlated significantly with whole kidney section
      tubular luminal space measurements, a correlate of water space, in the renal
      cortex, but only T1 in renal medulla showed a relationship to tubular luminal
      volume measured throughout the kidney. Urine and perchloric acid kidney extracts
      were studied using proton nuclear magnetic resonance (1H-NMR) spectroscopy to
      test the hypothesis that imaging differences implied specific urinary and tissue
      biochemical differences between affected and normal animals. 1H-NMR spectra of
      urine from cy/+ animals showed significantly increased excretion of alanine,
      citrate, succinate, and, 2-oxoglutarate but not methylamine compounds compared
      with +/+ animals. 1H-NMR spectra of aqueous perchloric acid kidney extracts
      confirmed reduced concentrations of the above ions and others involved in the
      citric acid cycle, as well the osmolytes betaine, taurine, and
      glycerophosphocholine PKD in the Han:SPRD-cy/+ rat is associated with distinct
      early MRI changes and alterations in urinary and tissue levels of organic anions
      and osmolytes.

PMID- 9039051
TI  - Internalization and apical-to-basolateral transport of folate in rat kidney
      proximal tubule.
AB  - Folate derivatives are filtered in the glomeruli and reabsorbed within the
      nephron. The amount filtered largely exceeds the minimum daily requirements. Thus
      folate reabsorbed within the kidney must be returned to the circulation. To
      establish whether renal proximal tubule can accomplish this by transport, of
      [3H]folate across the cell, microperfusion of rabbit, proximal tubule with
      [3H]folate and [14C]inulin was performed. Transtubular transport of [3H]folate
      was 5 +/- 1% (0.25 +/- 0.07 fmol/min) of perfused amount/mm tubule and remained
      constant during a 2-h perfusion period. An accumulation of 15 +/- 4% (0.8 +/- 0.3
      fmol/min) of perfused amount/mm tubule was observed during the same period.
      Furthermore, to determine whether endocytosis may be involved in the initial
      process of folate uptake in proximal tubule cells, we performed light microscopy
      autoradiography on cryosections of rat kidney cortex incubated with [3H]folate.
      Folate binding sites were located apically as well as intracellularly similar to
      the location of [3H]folate when injected into the abdominal aorta and visualized
      by light microscopy autoradiography. Thus folate binding sites as well as
      internalized folate is localized both apically and intracellularly. Micropuncture
      of rat proximal tubules with folate-coupled collodial gold particles showed
      significantly increased endocytosis of folate gold when evaluated quantitatively
      and compared with controls injected with noncoupled gold particles (0.22 +/- 0.08
      vs. 0.03 +/- 0.01 gold particles/micron 2 tubule cell). The results show that
      kidney proximal tubule cells are capable of transcellular transport of [3H]folate
      with limited capacity. Folate gold particle uptake suggests that folate can be
      internalized by endocytosis.

PMID- 9039052
TI  - Spatial and temporal expression of cell surface molecules during nephrogenesis.
AB  - Cell-to-cell interaction is fundamental to the development of the kidney.
      Ureteric bud cells, through cell contact or short-distance interactions, induce
      the metanephric mesenchyme to convert, to epithelia and begin the process of
      tubulogenesis. To identify new molecules that are involved in these processes, we
      generated a panel of monoclonal antibodies (MAbs) to the surface of induced
      mesenchymal cells taken from a day 15 rat embryonic kidney rudiment. MAbs were
      chosen for further study based either on a distinctive pattern of expression of
      their antigens or their functional effect on tubulogenesis. We identified a set
      of MAbs that preferentially stained the glomerular crevice, the first site for
      formation of the glomerular anlage. Another MAb inhibited tubulogenesis by
      producing widespread apoptosis in induced mesenchymal cells. This approach
      promises to identify new molecules that are central to kidney development.

PMID- 9039053
TI  - Downregulation of renal atrial natriuretic factor receptors and receptor mRNAs
      during rat pregnancy.
AB  - Using renal glomeruli and papillae from virgin, pregnant (15- to 17-day), and
      postpartum (day 2) rats, we investigated whether the decrease in the renal
      effects of atrial natriuretic factor (ANF) during pregnancy is caused by a
      downregulation of ANF receptors. Pregnancy decreased the maximal binding of 125I
      labeled ANF to guanylyl cyclase (GC)-linked ANF-GC receptors in glomeruli and
      papillae and increased the binding to clearance receptors (ANF-C) in glomeruli;
      ANF-C receptors were not detected in the papillae Ribonuclease protection assay
      detected mRNAs for all the three receptors in the papillae; pregnancy decreased
      GC-A and ANF-C but not GC-B-receptor mRNAs. Western blots revealed a decrease in
      GC-A receptors in the papillae of pregnant rats; GC-B-receptor protein was barely
      detectable. Effects of ANF on guanosine 3', 5'-cyclic monophosphate (cGMP)
      production by the glomeruli and papillae were decreased during pregnancy and
      returned to virgin levels during postpartum. It is concluded that a decrease in
      the renal effects of ANF during pregnancy is caused by a downregulation of renal
      ANF GC-A receptors and receptor-coupled cGMP production.

PMID- 9039055
TI  - Kinetics and osmoregulation of Na(+)-and Cl(-)-dependent betaine transporter in
      rat renal medulla.
AB  - Betaine is one of the major organic osmolytes that accumulate in the renal
      medulla in response to high extracellular tonicity. Recent studies in MDCK cells
      have shown that betaine is taken up by an Na(+)- and Cl(-)-dependent transporter
      located on the basolateral membrane. We demonstrate here the presence of Na(+)
      Cl(-)-dependent betaine transporter(s) in tubule suspensions prepared from the
      rat outer and inner medulla. The betaine transport activity was two to three
      times higher in the inner medulla compared with the outer medulla. The removal of
      Na+ and Cl- reduced betaine uptake in the outer medullary tubules by 86% and 82%,
      respectively. The betaine uptake was decreased by 39% in hypotonic buffer (189
      mosmol/ kgH2O) and increased by 82% in hypertonic buffer (545 mosmol/kgH2O),
      compared with isotonic buffer (308 mosmol/ kgH2O). Kinetic studies of Na(+)
      dependent betaine uptake in the outer medullary tubules revealed both a low- and
      a high-affinity component as follows: low-affinity and high volume component with
      Michaelis constant (K(m)1) of 8.6 mM and maximal uptake rate (Vmax1) of 112
      pmol.microgram protein-1.h-1; and a low-volume and high-affinity component with
      K(m)2 of 0.141 mM and Vmax2 of 10 pmol. microgram protein-1.h-1. To investigate
      whether the Na(+)-Cl(-)-dependent betaine transporter is regulated by tonicity in
      vivo, we quantitated its mRNA in rat renal cortex and outer and inner medulla
      using both canine and rat Na(+)-Cl(-)-dependent betaine transporter cDNA probes.
      A single band of 3.0 kb was seen in the Northern blots prepared from both outer
      and inner medulla, but not in the cortex. Water deprivation for 3 days increased
      the abundance of this mRNA in the outer and inner medulla by 140% and 170%,
      respectively, but did not affect its expression in the cortex. In conclusion,
      Na(+)-Cl(-)-dependent betaine transporter(s) is present in rat outer and inner
      medullary tubules, and betaine transporter mRNA abundance is regulated by the
      hydration state in vivo.

PMID- 9039054
TI  - Distribution of de novo synthesized betaine in rat kidney: role of renal
      synthesis on medullary betaine accumulation.
AB  - The trimethylamine glycine-betaine is accumulated to high concentrations in
      medullary cells of mammalian kidneys, whereas betaine synthesis from choline is
      predominant in the renal cortex. We investigated the contribution of renal
      betaine synthesis to medullary betaine accumulation. De novo synthesis of betaine
      in situ was accomplished by injecting [14C]choline into the renal artery of male
      Sprague-Dawley rats. [14C]betaine was measured in the renal cortex and medulla,
      as well as in serum and urine samples. Betaine concentration in the cortex
      decreased from 3.5 +/- 1.3 at 5 min to 0.4 +/- 0.2 nmol/mg protein at 60 min, but
      it increased from 1.4 +/- 0.1 to 2.5 +/- 0.6 nmol/mg protein in the medulla.
      Serum and total urine [14C]betaine increased from 2.7 +/- 1.3 and 0.9 +/- 0.1
      nmol/ml at 5 min to 5.3 +/- 0.3 and 2.1 +/- 0.4 nmol/ml at 60 min, respectively.
      Concentrations of newly synthesized betaine were not decreased by the ligation of
      the hepatic artery and portal vein, suggesting that most [14C]betaine was
      synthesized in the kidney. Coinjection with 5 mM dimethylamino-ethanol, a choline
      oxidase inhibitor, and 100 mM cold betaine reduced medullary betaine accumulation
      by 80 and 76%, respectively. Water deprivation for 60 h increased both cortical
      and medullary [14C]betaine, whereas furosemide diuresis decreased the medullary
      [14C]betaine concentration. We concluded that betaine synthesized in the kidney
      can be accumulated in the medulla and that the medullary concentrations of newly
      synthesized betaine are closely related to the hydration state of the animal.

PMID- 9039056
TI  - Renal alterations of atrial natriuretic peptide receptors by chronic moderate
      ethanol treatment.
AB  - Previous studies have shown that chronic moderate ethanol (EtOH) consumption
      prevents the age-dependent increase in blood pressure. However, the physiological
      systems mediating the antihypertensive effects of EtOH are not known. The
      objective of the present studies was to investigate the effects of chronic (8 mo)
      moderate EtOH consumption on renal natriuretic receptors of spontaneously
      hypertensive (SHR) and normotensive (WKY) rats, using competitive binding assay
      and autoradiographic techniques. In the renal glomeruli, the maximal binding
      capacity (Bmax) of the heterogeneous atrial natriuretic peptide (ANP) receptor
      population (NPR-A and NPR-C) was significantly lower in EtOH-treated SHR and WKY
      rats compared with water-treated controls. Quantification of receptor subtypes
      showed that this decrease was primarily the result of NPR-C down-regulation. The
      apparent dissociation constant (Kd) was also decreased by the EtOH treatment. In
      the renal papilla, the Bmax of the homogeneous receptor population (NPR-A) was
      significantly elevated by long-term EtOH consumption in both strains compared
      with water-treated controls. However, the Kd was unaltered by the EtOH
      administration. Thus EtOH treatment induced specific alterations in renal
      natriuretic receptors that may play a role in the "protective" effect of moderate
      EtOH consumption on the age-dependent increase in blood pressure.

PMID- 9039057
TI  - Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of
      megalin.
AB  - Megalin, a giant glycoprotein receptor heavily concentrated in the early
      endosomal pathway of renal proximal tubular cells, binds gentamicin with high
      affinity and delivers the drug to lysosomes. Utilizing an in vitro reconstitution
      assay we tested whether gentamicin-induced vacuolation is associated with
      inhibition of early endosomal fusion, as well as whether megalin plays a role in
      mediating these effects. Pretreatment of rats with gentamicin inhibited rat renal
      proximal tubular homotypic endosomal fusion. Administered simultaneously,
      gentamicin and polymers of polyaspartic acid, which protect against the
      hemodynamic effects of gentamicin nephrotoxicity, had no net effect on fusion.
      Polyaspartic acid alone had no effect on fusion. Antisera to the tail of the
      megalin/gentamicin receptor inhibited fusion, whereas non-specific controls had
      no effect. Peptides matching homologous NPXY repeat sequence motifs in the
      cytosolic tail stimulated endosomal fusion, whereas reverse sequence control
      peptides had no effect. These data suggest that gentamicin inhibition of
      endosomal fusion in the renal proximal tubule is a damage mechanism mediated by
      specific peptide sequences in the cytosolic tail of the giant gentamicin-binding
      receptor megalin and that receptors can effect the fusion properties of membranes
      in which they reside.

PMID- 9039058
TI  - K depletion modifies the properties of Sch-28080-sensitive K-ATPase in rat
      collecting duct.
AB  - Two distinct Sch-28080-sensitive K-adenosine triphosphatases (K-ATPases) were
      previously described in the rat nephron: a ouabain-resistant K-ATPase (type I)
      present in collecting ducts (CD) and a ouabain-sensitive from (type II) located
      in proximal tubules (PT) and thick ascending limbs (TAL). In K-depleted rats, K
      ATPase activity is increased in CD, whereas it is reduced in PT and TAL. Because
      expression of colonic H-K-ATPase is restricted to the CD of K-depleted rats, we
      hypothesized that K-ATPase from the CD of K-depleted rats might be different from
      types I and II. Indeed, type III K-ATPase displays higher sensitivities to
      ouabain and to Sch-28080 than type II, a lower sensitivity to Sch-28080 than type
      I, and, conversely to types I and II, it can be stimulated by Na+.
      Pharmacological differences between types II and III K-ATPases were confirmed by
      [3H]ouabain binding experiments. Thus the rat kidney expresses three K-ATPases
      that differ by their pharmacological and kinetic properties, their distribution
      profile along the nephron and their behavior during K depletion.

PMID- 9039059
TI  - Analysis and modeling of the primary cilium bending response to fluid shear.
AB  - Since a nonmotile, primary (9 + 0) cilium projects from most mammalian kidney
      epithelial cells into the tubule lumen, where it is exposed to fluid motion, the
      present study examined primary cilium response to fluid shear stress. The
      reversible, large-angle bending of the primary cilium upon exposure to fluid
      shear forces (10(-11)-10(-10) N.m2 = 10(-8)-10(-7) dyn/cm) was characterized in
      vitro using videomicroscopic side views of PtK1 cells, and the cilium was then
      mathematically modeled as a cantilevered beam. The flexural rigidity of the
      primary cilium was calculated to be 3.1 +/- 0.8 x 10(-23) N.m2 with a corrected
      quadruple integration approach and 1.4-1.6 x 10(-23) N.m2 with the "heavy
      elastica" theory. Comparison of theoretical profiles to the experimental bending
      responses of cilia established the validity of the "heavy elastica" model; this
      model, in turn, was used to predict primary cilium bending behavior under
      representative conditions in the rat nephron. The results of the study are
      consistent with the hypothesis that primary cilia serve a mechanosensory function
      in kidney epithelial cells.

PMID- 9039060
TI  - Transforming growth factor-beta selectively inhibits branching morphogenesis but
      not tubulogenesis.
AB  - When cultured in type I collagen gels, two kidney-derived cell lines, Madin-Darby
      canine kidney (MDCK) cells and murine inner medullary collecting duct (mIMCD3)
      cells, from branching tubular structures in the presence of Swiss 3T3 conditioned
      medium, in which hepatocyte growth factor (HGF) is the major branching tubule
      inducing factor. However, upon incubation with transforming growth factor-beta
      (TGF-beta) in the presence of 3T3 conditioned medium, MDCK tubulogenesis and
      branching was markedly inhibited. In contrast, mIMCD3 cells, which are much less
      susceptible to growth and tubulogenesis inhibition by TGF-beta, formed long
      straight tubulelike structures in presence of TGF-beta, suggesting a dissociation
      between tubulogenesis and branching morphogenesis. Interestingly, those long
      tubules that did branch often superficially resembled the early branching
      ureteric bud in embryonic kidneys. Quantitation of branching events revealed a
      selective branch-inhibiting effect of TGF-beta on mIMCD3 cells at concentrations
      between 0.02 and 2 ng/ml. There was no qualitative or quantitative difference
      among TGF-beta 1, -beta 2, and -beta 3 on inhibition of branching events,
      suggesting existence of potentially redundant mechanisms for modulating branching
      morphogenesis. Concentrations of TGF-beta that resulted in long nonbranching
      tubules also altered the profile of extracellular matrix-degrading proteases and
      their inhibitors expressed by developing tubules. Ratios of urokinase type
      plasminogen activator (u-PA) to plasminogen activator inhibitor (PAI-l) and
      matrix metalloprotease (MMP)-1 to tissue inhibitor of metalloprotease (TIMP)-1
      were both markedly decreased. In addition, apart from a direct effect on
      epithelial cell branching morphogenesis, TGF-beta downregulated the expression of
      HGF mRNA in Swiss 3T3 cells. Thus TGF-beta exerts at least three distinct effects
      relevant to tubulogenesis and branching morphogenesis inhibition of branching
      morphogenesis alone (mIMCD3 cells), inhibition of both tubulogenesis and
      branching morphogenesis (MDCK cells), and inhibition of the expression of growth
      factor which induce tubulogenesis and branching morphogenesis (3T3 cells). In the
      context of epithelial tissue development, which requires tightly regulated
      branching tubulogenesis of epithelial cells, the data suggest a model where
      branching patterns are regulated by a precise temporal and spatial balance
      between branching morphogens such as HGF and inhibitory morphogens such as
      members of the TGF-beta superfamily [e.g., TGF-beta isoforms, certain bone
      morphogenetic proteins].

PMID- 9039061
TI  - Vasopressin constricts outer medullary descending vasa recta isolated from rat
      kidneys.
AB  - Arginine vasopressin (AVP) can selectively decrease blood flow in the renal
      medulla, but the sites of vasoconstriction are uncertain. We have examined the
      effects of vasopressin-receptor agonists and antagonists on the diameters of
      outer medullary descending vasa recta (OMDVR), isolated and perfused in vitro.
      AVP can constrict OMDVR, apparently via V1a-receptors. Ablumenal AVP (10(-10)-10(
      6)M) or the selective V1a-receptor agonist [Phe2, Ile3, Orn8]-vasopressin (PO-VT,
      10(-8) M) constricted OMDVR focally and (at higher AVP concentrations)
      transiently. The V1b agonist ideamino-Cys1,D-3-(pyridyl)Ala2,Arg8)vasopressin (DP
      VP; 10(-8) M) and the V2 agonist [deamino-Cys1, D-Arg8]vasopressin (DDAVP; 10(-8)
      M) did not constrict OMDVR. The V1a antagonist [d(CH2)5(1), O-Me
      Tyr2,Arg8]vasopressin (CTM-VP, 10(-10) 10(-8) M) inhibited vasoconstriction by
      AVP 10(-9 M), whereas the V2 antagonist [d(CH2)5(1), D-Ile2,Ile4 Arg8]vasopressin
      (II-VP) at low concentration (10(-10) M) did not. V2 stimulation seems to inhibit
      V1a constriction of OMDVR. DDAVP prevented constriction by PO-VT (10(-8) M)
      applied at the same time and dilated OMDVR preconstricted with PO-VT.

PMID- 9039062
TI  - Reference-based pricing of prescription drugs.

PMID- 9039063
TI  - A position paper on drug-pricing strategies for prescription pharmaceuticals in
      Canada. Canadian Cardiovascular Society.

PMID- 9039064
TI  - Reference-based pricing in British Columbia: implications for cardiologists--an
      analysis.
AB  - Under the reference-based pricing (RBP) policy, British Columbia will fund drug
      therapies based on the cost of the 'gold standard' therapy that meets the needs
      of the majority of patients with a specific condition. Hence, Pharmacare will pay
      for the lowest cost drug within a cluster of related but different drugs,
      regardless of the indication. When evaluating the impact of drugs on health care
      expenditure, one must consider that their costs are more than offset by the
      clinical and economic benefits they provide. Pharmaceutical expenditure accounts
      for a small proportion of health care expenditure and should be viewed as an
      essential and interactive component in the global health care budget rather than
      as an independent constituent. In that respect, insight should be gained from
      many countries in which RBP has been implemented A wealth of data converge to the
      same conclusion: price controls and restricted access to drugs do not reduce
      prescription drug expenditures but actually increase health care costs.
      Furthermore, cost containment being the main issue behind RBP in British
      Columbia, the contentious issue of therapeutic substitution has not been taken
      fully into consideration, nor has its impact on the quality of care of the
      patient. The case of diltiazem once-a-day versus diltiazem tablets for
      hypertensive and angina patients illustrates the important considerations that
      must be taken into account in writing the overall financial equation that drives
      the implementation of the RBP policy. If pharmacotherapy is to be an appropriate
      treatment to attain optimal cost effective health care, its benefit can only be
      optimized with a strategy that entails the right therapy, for the right patient,
      in the right dosage form and at the right time. Accordingly, RBP in British
      Columbia should be analyzed in light of patient welfare and appropriate use of
      collective resources.

PMID- 9039065
TI  - Sotalol-induced torsades de pointes in patients with renal failure.
AB  - The risk of torsades de pointes in patients on sotalol is increased in the
      setting of renal failure. QT dispersion and prolonged QT intervals have been
      described as markers for pro-arrhythmia. Four cases of torsades de pointes caused
      by low dose sotalol in patients with renal failure are reported. All four cases
      demonstrated that the 12-lead electrocardiogram, with markedly prolonged QT
      intervals and increased QT dispersion, could have been used to predict pro
      arrhythmia.

PMID- 9039066
TI  - The management of acute myocardial infarction in a patient with polycythemia
      rubra vera during the thrombolytic era--does it make a difference?
AB  - A 42-year-old man presented with acute anterior myocardial infarction and
      hemoglobin of 248 g/L. Laboratory studies suggested the diagnosis of polycythemia
      rubra vera (PRV). Management of this condition with acetylsalisylic acid,
      heparin, warfarin and phlebotomy constitutes a therapeutic dilemma. This case
      also brings up the question of the appropriateness of thrombolysis and
      angioplasty in the treatment of myocardial infarction in the presence of PRV. Due
      to the rarity of this hematological disease, a call for international
      collaboration for assessing the efficacy and safety of these treatment modalities
      is recommended.

PMID- 9039067
TI  - Lipomatous metaplasia in left ventricular scar.
AB  - BACKGROUND AND OBJECTIVE: Substitution of interstitial tissue by fat may be
      observed in the right ventricle of hearts but is less common in the left
      ventricle. Fat was noted in myocardial scars of patients undergoing heart
      transplantation, prompting this retrospective study to determine the frequency of
      left ventricular myocardial scar being replaced by fat and its significance
      METHODS AND RESULTS: The left and right ventricles and coronary arteries were
      sampled systematically and lesions quantified histologically in 97 normal
      subjects dying accidentally; 116 consecutive failing hearts excised at
      transplantation from patients with ischemic heart disease, idiopathic dilated
      cardiomyopathy or chronic valvulopathy; and 34 autopsy hearts of apparently
      normal subjects with "silent' Chagas' heart disease who died suddenly and
      unexpectedly. Twenty-two left ventricular aneurysmectomy specimens from ischemic
      patients with heart failure were also studied. Among excised hearts lipomatous
      metaplasia of myocardial scar was observed in 68% of ischemic heart disease, in
      37% of chronic valvulopathy and in 26% of idiopathic dilated cardiomyopathy
      patients; it was seen in 15% of Chagasic patients and in 55% of aneurysm walls.
      CONCLUSIONS: Lipomatous metaplasia of scar is often associated with severe heart
      failure and is more frequent and extensive in ischemic heart disease.
      Transformation of a compact scar into compressible and "sliding' adipose tissue
      may worsen ventricular wall function, thus facilitating and/or aggravating
      aneurysm formation. This phenomenon must be considered in the evaluation of
      myocardial repair, cardiac imaging of viable myocardium, quantitative morphology
      of autopsy specimens, and qualitative and quantitative biochemical analysis of
      myocardial tissue.

PMID- 9039068
TI  - Rapid enlargement of cardiac rhabdomyoma during corticotropin therapy for
      infantile spasms.
AB  - OBJECTIVE: To investigate the influence of corticotropin therapy on cardiac
      rhabdomyoma. DESIGN: Analysis of data from echocardiography performed on in
      patients. PATIENTS: Six patients with rhabdomyoma who were admitted to the
      authors' medical centre with either convulsion (five cases) or prematurity (one
      case) between 1985 and 1995. Five had tuberous sclerosis. INTERVENTION: Size of
      cardiac tumours of each patient was measured by echocardiography, and volume
      index was calculated as the ratio of the tumour volume to its initial volume.
      MAIN RESULT: Increase in size of some of the tumours was found during
      corticotropin therapy on follow-up echocardiography. Maximum volume indexes of
      tumours in the case of patients (n = 4) who did not receive corticotropin therapy
      was 1.2 to 3.7, whereas those of patients (n = 2) who received therapy was 9.1 to
      12; one of the latter patients died. CONCLUSION: Corticotropin may contribute to
      the enlargement of cardiac rhabdomyoma. The size of cardiac rhabdomyomas must be
      carefully followed when patients are treated with corticotropin.

PMID- 9039069
TI  - Are psychotropic drugs at therapeutic levels a concern for cardiologists?
AB  - OBJECTIVE: To review the cardiovascular effects of psychotropic drugs when used
      in therapeutic doses and to assess their clinical relevance for cardiologists.
      Information on newer psychopharmacological agents is also presented. DATA
      SOURCES: MEDLINE was used to search the relevant English language medical
      literature over the past five years. Standard texts and selected earlier
      references were also used. Input was obtained from local experts. DATA SYNTHESIS:
      Many antipsychotics and antidepressants have the potential for causing malignant
      ventricular arrhythmias and cardiac conduction disturbances. Postural hypotension
      is also a common side effect with important associated morbidity. The effects of
      psychotropic drugs on myocardial contractile properties are not significant at
      therapeutic dose levels. Older agents, such as phenothiazines, tricyclic
      antidepressants and monoamine oxidase inhibitors, are responsible for most of the
      reported adverse cardiovascular effects of psychotropic drugs. Selective
      serotonin reuptake inhibitors are a newer class of antidepressants that are free
      from significant direct cardiovascular adverse effects; however, if combined with
      other agents such as the monoamine oxidase inhibitors, they can cause
      cardiovascular collapse as part of a potentially fatal 'serotonin syndrome'.
      These newer agents can also exaggerate the actions of certain cardiac drugs
      through effects on their metabolism by inhibition of cytochrome P450 isoenzymes.
      CONCLUSION: The adverse cardiovascular effects of psychotropic medications in
      therapeutic doses are a valid concern for cardiologists. Familiarity with these
      drugs and their interactions is essential to avoid important undesired reactions
      with potential fatal consequences.

PMID- 9039070
TI  - Feasibility and complications of single-plane and biplane versus multiplane
      transesophageal imaging: a review of 2947 consecutive studies.
AB  - OBJECTIVE: To analyze and compare the incidence of procedural complications and
      failure of intubation with various sizes of probes used in transesophageal
      echocardiography. DESIGN: Retrospective chart review. SETTING: A Canadian,
      tertiary care hospital. PATIENTS: A total of 2947 consecutive transesophageal
      echocardiographic patient examinations between January 1992 and March 1996 at the
      University of Ottawa Heart Institute, Ottawa, Ontario. RESULTS: The multiplane
      probe (MP) was used in 1274 studies, biplane (BP) in 1642 and single plane (SP)
      in 31. Data for BP and SP were combined because of their similar size.
      Complications or failed intubation occurred in 86 studies (2.9%). There were 53
      complications (1.8%) and 40 failed intubations (1.4%). Seven patients (0.3%) had
      both. Complications were death in one, tracheal intubation or bronchospasm in
      nine, bleeding in nine, angina in two, pulmonary edema in two, superficial
      thrombophlebitis in two, supraventricular tachycardia in one and minor adverse
      events in 27. Complications were unrelated to the choice of probe (MP 2%, BP and
      SP 1.7%, not significant). Failure of intubation (40 cases) was more common with
      MP than with BP and SP (2.3% versus 0.7%, P = 0.0003, OR 3.5, 95% CI 1.7 to 7.5).
      The main reasons for failure were cervical spondylosis in 16 patients and
      hypersensitive pharynx despite topical anesthesia and sedation in 13 patients. Of
      21 cases of failed MP intubation, 16 (76%) were subsequently successful with BP.
      CONCLUSIONS: Serious complications with transesophageal echocardiography,
      although infrequent, do occur. The MP carries a 3.5-fold increased risk of failed
      intubation. In the majority of failures, successful intubation can be achieved
      with a smaller probe.

PMID- 9039071
TI  - The relationship between the sinus node and the right atrial appendage.
AB  - BACKGROUND: The developmental anatomy of the right atrium, particularly the union
      between its sinus venarum (sinus) and atrial portions, has not been completely
      settled. Invagination of the embryonic sinus into the atrium brings about
      electrical and structural union between these primitive chambers but results in
      the formation of the terminal crest, a seemingly bulky and intrusive band of
      muscle separating sinus from atrium. However, it is unlikely that a structure
      that can be found in all mammalian species is merely a functionless remnant.
      Structural differences between the smooth sinus and the deeply trabeculated right
      atrial appendage emphasize the two-part shape of the right atrium, but it is
      hypothesized that the sinus and atrium form a single, well-knit chamber shaped
      for the supply of nutrient blood to atrial conducting tissues rather than for
      downstream bloodflow. METHODS AND RESULTS: The morphology of the right atrium was
      studied grossly and microscopically in 54 adult hearts. The distribution of
      Thebesian sinusoids arising from the right atrial appendage was identified by ink
      perfusion and clearing of several additional adult and fetal hearts. The sinus
      node was found to be precisely co-extensive with the undercut portion of the
      terminal crest and with pectinate muscles lining the pyramidal portion of the
      right atrial appendage. Sinusoids and interpectinate spaces related to the
      undercut portion of the terminal crest are limited to the area of the sinus node.
      CONCLUSION: These findings support the hypothesis that the right atrial
      appendage, pectinate muscles and terminal crest evolved to supply nutrient blood
      to conducting myocardium of the sinus portion of the right atrium, and that this
      chamber, like the right ventricle, is structured as a single and completely
      finished unit. Interpectinate spaces and Thebesian sinusoids offer clues to the
      location of conducting pathways, including the sinus node.

PMID- 9039072
TI  - Influence of lifestyle, coping, and job stress on blood pressure in men and
      women.
AB  - We designed this study to clarify the role of work stress on long-term blood
      pressure control and in particular to investigate whether perceived work stress
      directly affected resting blood pressure levels or whether there were indirect
      effects mediated by coping mechanisms and lifestyle. Men (n = 337) and women (n =
      317) working in a government tax office completed questionnaires for assessment
      of work-related stress, coping strategies, and lifestyle. Seven resting blood
      pressure measurements were recorded serially on each of two occasions a week
      apart. Men had higher blood pressures (119.6/68.6 versus 110.9/65.6 mm Hg) than
      women; they used more "maladaptive" coping strategies, drank more alcohol, and
      ate less healthily but exercised more than women. There were no direct
      associations between measures of work stress and blood pressure. In univariate
      and regression analyses, both body mass index and lifestyle factors in the form
      of alcohol consumption, exercise, and diet were related to blood pressure in men
      and women. Various "adaptive" or "maladaptive" coping mechanisms were identified
      and independently related to both job stress and blood pressure levels. Women
      were more likely to use "healthier" or adaptive coping mechanisms than men. Thus,
      work stress per se had no direct effect on blood pressure, but the ways that
      individuals reported coping with stress were significantly related to blood
      pressure, with blood pressure elevation effects appearing to be mediated largely
      by dietary and drinking habits and physical inactivity. The results point to the
      need to target individual coping strategies and lifestyle as much as the working
      environment in workplace cardiovascular health promotion programs.

PMID- 9039073
TI  - Long-term effects on sexual function of five antihypertensive drugs and
      nutritional hygienic treatment in hypertensive men and women. Treatment of Mild
      Hypertension Study (TOMHS)
AB  - Problems with sexual function have been a long-standing concern in the treatment
      of hypertension and may influence the choice of treatment regimens and decisions
      to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides
      an excellent opportunity for examination of sexual function and effects of
      treatment on sexual function in men and women with stage I diastolic hypertension
      because of the number of drug classes studied, the double-blind study design, and
      the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of
      902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated
      with placebo or one of five active drugs (acebutolol, amlodipine maleate,
      chlorthalidone, doxazosin maleate, or enalapril maleate). All participants
      received intensive lifestyle counseling regarding weight loss, dietary sodium
      reduction, alcohol reduction (for current drinkers), and increased physical
      activity. Sexual function was ascertained by physician interviews at baseline and
      annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a
      problems with sexual function. In men, 12.2% had problems obtaining and/or
      maintaining an erection; 2.0% of women reported a problem having an orgasm.
      Erection problems in men at baseline were positively related to age, systolic
      pressure, and previous antihypertensive drug use. The incidences of erection
      dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months,
      respectively, and were related to type of antihypertensive therapy. Participants
      randomized to chlorthalidone reported a significantly higher incidence of
      erection problems through 24 months than participants randomized to placebo
      (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more
      similar among treatment groups than at 24 months, with nonsignificant differences
      between the chlorthalidone and placebo groups. Incidence was lowest in the
      doxazosin group but was not significantly different from the placebo group.
      Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in
      the placebo group. In many cases, erection dysfunction did not require withdrawal
      of medication. Disappearance of erection problems among men with problems at
      baseline was common in all groups but greatest in the doxazosin group. Incidence
      of reported sexual problems in women was low in all treatment groups. In
      conclusion, long-term incidence of erection problems in treated hypertensive men
      is relatively low but is higher with chlorthalidone treatment. Effects of
      erection dysfunction with chlorthalidone appear relatively early and are often
      tolerable, and new occurrences after 2 years are unlikely. The rate of reported
      sexual problems in hypertensive women is low and does not appear to differ by
      type of drug. Similar incidence rates of erection dysfunction in placebo and most
      active drug groups caution against routine attribution of erection problems to
      antihypertensive medication.

PMID- 9039074
TI  - Senescent heart compared with pressure overload-induced hypertrophy.
AB  - Although systolic left ventricular (LV) function is normal in the elderly, aging
      is associated in rat papillary muscle with mechanical and sarcoplasmic reticulum
      Ca2+ ATPase alterations similar to those observed in the hypertrophied heart.
      However, alterations in the other calcium-regulating proteins implicated in
      contraction and relaxation are still unknown. To investigate alterations in LV
      function and calcium-regulating proteins, we measured hemodynamics and Na(+)-Ca2+
      exchanger (NCx), ryanodine receptor (RyR2), and sarcoplasmic reticular Ca2+
      ATPase (SERCA2) mRNA levels (expressed in densitometric scores normalized to that
      of poly(A+) mRNA) in left ventricle from 4-month-old (adult, n = 13) and 24-month
      old (senescent, n = 15) rats. For ex vivo contractile function, active tension
      was measured during isolated heart perfusion in adult (n = 11) and senescent (n =
      11) rats. For comparison of age-dependent effects of moderate hypertension on
      both hemodynamics and calcium proteins, renovascular hypertension was induced or
      a sham operation performed at 2 (n = 11 and n = 6) and 22 (n = 26 and n = 5)
      months of age. In senescent rats, LV systolic pressure and maximal rates of
      pressure development were unaltered, although active tension was depressed (4.7
      +/- 0.4 versus 8.3 +/- 0.7 g/g heart weight in adults, P < .0001). SERCA2 mRNA
      levels were decreased in senescent left ventricle (0.98 +/- 0.05 versus 1.18 +/-
      0.05 in adults, P < .01), without changes in NCx and RyR2 mRNA accumulation.
      Renovascular hypertension resulted in 100% mortality in aged rats; in adults,
      renovascular hypertension resulted, 2 months later, in an increase of LV systolic
      pressure (170 +/- 7 versus 145 +/- 3 mm Hg in sham-operated rats, P < .05) and in
      mild LV hypertrophy (+18%, P < .01) associated with a decrease in SERCA2 mRNA
      levels (1.02 +/- 0.03 versus 1.18 +/- 0.03 in sham-operated rats, P < .001).
      Contractile dysfunction in senescent isolated heart and decreased SERCA2 mRNA
      levels were associated with in vivo normal LV function at rest, indicating the
      existence of in vivo compensatory mechanisms. RyR2 and NCx gene expressions were
      not implicated in the observed contractile dysfunction. In aged rats,
      renovascular hypertension resulted in 100% mortality, probably related to
      elevated levels of circulating angiotensin II, whereas in adult rats,
      renovascular hypertension induced a mild LV hypertrophy associated with a
      selective alteration in SERCA2 gene expression.

PMID- 9039075
TI  - Prediction of cardiac structure and function by repeated clinic and ambulatory
      blood pressure.
AB  - We performed imaging echocardiography, Doppler velocimetry, and repeated clinic
      and ambulatory blood pressure measurements in 74 hypertensive individuals to
      clarify why reports differ on the strength of the relationships of left
      ventricular characteristics with clinic blood pressure, on the superiority of
      ambulatory over clinic pressure, and on the importance of day-time and nighttime
      pressures. Clinic pressure was measured five times with an automated device and
      five times with the conventional technique on 2 different days. The partial
      correlation coefficients of left ventricular mass and wall thickness with the
      first automated systolic and diastolic clinic pressures amounted to .38 to .45 (P
      < .001), improved with increasing numbers of measurements, and reached .56 to .58
      for the average of 10 automated pressure determinations. Similar trends were
      observed for conventional clinic pressures. Average 24-hour pressures were
      significantly related to mass and wall thickness (partial r = .50 to .61, P <
      .001) and explained 3% to 6% (systolic) and 5% to 12% (diastolic) of the variance
      of cardiac structure in addition to the first automated or conventional clinic
      pressure (P < .05). However, when 10 clinic measurements were averaged, only
      diastolic 24-hour pressure added information over and above clinic pressure (P <
      .05); the additional explained variance was larger with regard to the
      conventional (+4% for mass and +7% for wall thickness) rather than the automated
      (+3% for wall thickness only) pressures. Mass and wall thickness were more
      closely related to day-time than nighttime pressures and were not independently
      related to day-night differences in pressure, except when men and women were
      considered separately; the results were similar when four different definitions
      of day and night were applied. Finally, the weak association of left ventricular
      diastolic function with blood pressure did not improve on repeated clinic or
      ambulatory blood pressure measurements. In conclusion, increasing numbers of
      measurements strengthen the relationships of clinic pressure with left
      ventricular mass and wall thickness and, conversely, diminish the additional
      predictive power of 24-hour blood pressure. The importance of nighttime pressure
      and of the nighttime pressure fall does not seem to depend on the definition of
      day and night but differs in men and women.

PMID- 9039076
TI  - Nocturnal blood pressure fall on ambulatory monitoring in a large international
      database. The "Ad Hoc' Working Group.
AB  - A wide range of definitions is used to distinguish subjects in whom blood
      pressure (BP) falls at night (dippers) from their counterparts (nondippers). In
      an attempt to standardize the definition of nondipping, we determined the
      nocturnal BP fall and night-day BP ratio by 24-hour ambulatory monitoring in 4765
      normotensive and 2555 hypertensive subjects from 10 to 99 years old. In all
      subjects combined, the systolic/diastolic nocturnal fall and corresponding ratio
      averaged (+/- SD) -16.7 +/- 11.0/ -13.6 +/- 8.1 mm Hg and 87.2 +/- 8.0%/83.1 +/-
      9.6%, respectively. In normotensive subjects, the 95th percentiles were -0.3/-1.1
      mm Hg for the nocturnal fall and 99.7%/98.3% for the night-day ratio. Both the
      fall and ratio showed a curvilinear correlation with age. The smallest fall and
      largest ratio were observed in older (> or = 70 years) subjects. A higher BP on
      conventional sphygmomanometry was associated with a larger systolic (partial r =
      .11) and diastolic (r = .12) nocturnal BP fall. The diastolic (r = .08) but not
      the systolic night-day ratio increased with higher conventional BP. The nocturnal
      BP fall was larger and the corresponding night-day ratio smaller in oscillometric
      (n = 5884) than in auscultatory (n = 1436) recordings, in males (n = 3730) than
      in females (n = 3590), and in Europe (n = 4556) than in the other continents (n =
      2764). The distributions of the nocturnal BP fall and night-day ratio showed
      considerable overlap among normotensive and hypertensive subjects, but the
      overlap tended to be larger for the ratio than for the fall. Of all subjects,
      3.2% had systolic and diastolic ratios of 100% or more. With adjustments applied
      for confounders, the probability of being a nondipper increased 2.8 times (95%
      confidence interval, 2.0-4.0) from 30 to 60 years and 5.7 times (4.4-7.4) from 60
      to 80 years. The odds ratios were 1.0 (0.8-1.4) for males versus females. 1.6
      (1.2-2.1) for subjects with definite hypertension versus normotensive subjects,
      2.4 (1.2-4.7) for Asians (n = 2213, 96% Japanese) versus inhabitants of the other
      continents, and 2.4 (1.5-3.8) for subjects examined with auscultatory versus
      oscillometric devices. In conclusion, the mathematical definition of nondipping,
      ie, having a night-day ratio of 100% or more for systolic and diastolic BPs,
      closely approximated the 95th percentiles of the night-day ratio in normotensive
      subjects. The ratio depends less on BP level than the nocturnal BP fall and is
      therefore to be preferred in the definition of dipping status. Notwithstanding
      the present findings, the reproducibility of nondipping and its prognostic
      significance need further clarification.

PMID- 9039077
TI  - Association of serum antibodies to heat-shock protein 65 with borderline
      hypertension.
AB  - Heat-shock proteins protect cells from damage but are also often the target of
      immune responses in inflammation and may therefore both induce and perpetuate the
      chronic inflammation characterizing atherosclerosis. Hypertension is a well
      established risk factor for atherosclerosis, and recently, borderline
      hypertension also has been related to atherosclerosis. The present study
      investigated the possible role of heat-shock proteins in borderline hypertension
      and their relation to atherosclerosis by investigating antibody titers against
      the 65-kD heat-shock protein (HSP65). Sixty-six men with borderline hypertension
      and 67 age-matched normotensive men (diastolic pressure, 85 to 94 and < 80 mm Hg,
      respectively) were recruited from a population screening program. Titers of
      antibodies to HSP65 were determined by enzyme-linked immunosorbent assay. The
      presence of carotid atherosclerosis was determined by B-mode ultrasonography.
      Twenty-seven individuals had atherosclerotic plaques: 48 were smokers (more than
      one to two cigarettes per day). Borderline hypertensive men had higher anti-HSP65
      reactivity than normotensive control subjects (P = .034). Smokers with
      atherosclerosis had low levels of antibodies to HSP65 compared with nonsmokers
      with atherosclerosis (P = .002). Furthermore, when high-risk individuals
      (borderline hypertension plus plaque, n = 15) were compared with matched low-risk
      individuals (normotensive with no plaque, n = 15), the high-risk men had
      significantly enhanced antibody titers to HSP65 (P = .041). In conclusion, we
      demonstrate that serum antibody titers to HSP65 are enhanced in individuals with
      borderline hypertension, which may indicate an ongoing immune reaction in the
      artery wall.

PMID- 9039078
TI  - Vascular aldosterone in genetically hypertensive rats.
AB  - We have reported that aldosterone is synthesized and cytochrome P450aldo mRNA
      exists in the vasculature. To clarify the pathophysiological role of vascular
      aldosterone in hypertension, we compared aldosterone production in the mesenteric
      arteries of stroke-prone spontaneously hypertensive rats (SHRSP) with that in
      Wistar-Kyoto rats (WKY). The expressions of mRNA of cytochrome P450aldo,
      mineralocorticoid receptor, and alpha 1, Na,K-ATPase in the mesenteric arteries
      were compared between the two groups. Aldosterone concentration in the perfusate
      of the vasculature was measured by radioimmunoassay after purification with high
      performance liquid chromatography. Cytochrome P450aldo and mineralocorticoid
      receptor mRNA levels were quantified by Southern blot analysis of the products of
      reverse-transcribed polymerase chain reaction. Levels of alpha 1 Na,K-ATPase mRNA
      were measured by Northern blot analysis. Vascular aldosterone and cytochrome
      P450aldo mRNA levels of 2-week-old SHRSP were significantly increased compared
      with those of age-matched WKY. However, vascular aldosterone in 4- and 9-week-old
      SHRSP did not differ from that in age-matched WKY. Expression levels of
      mineralocorticoid receptor mRNA in the vasculature of 4- and 9-week-old SHRSP
      were significantly increased compared with those in age-matched WKY.
      Concentrations of vascular alpha 1 Na,K-ATPase mRNA of 2-, 4-, and 9-week-old
      SHRSP also were significantly higher than those in age-matched WKY. These results
      suggest that vascular aldosterone contributes to the pathophysiology of
      hypertension in SHRSP in the early stage.

PMID- 9039079
TI  - Absence of linkage for "endothelial" nitric oxide synthase locus to blood
      pressure in Dahl rats.
AB  - Nitric oxide is thought to be involved in blood pressure regulation. Nitric oxide
      synthase (NOS) genes are logical candidates for genetic hypertension. Of the
      three known forms of NOS, the "neuronal" and "inducible" Nos genes have been
      tested as candidate genes for causing inherited hypertension in Dahl salt
      sensitive rats. In the present work, we analyzed the endothelial Nos gene,
      designated Nos3, directly and indirectly for cosegregation with blood pressure in
      six F2 populations independently generated from crosses of Dahl salt-sensitive
      rats with rats of various other strains. The Nos3 alleles did not cosegregate
      with blood pressure in these populations. Therefore, Nos3 is an improbable, if
      not impossible, candidate gene for causing hypertension in the Dahl salt
      sensitive rat.

PMID- 9039080
TI  - Amplification of kinin-induced hypotension by nitric oxide synthesis in
      spontaneously hypertensive rats.
AB  - We studied the role of nitric oxide and adrenergic activation in the blood
      pressure (BP) response to exogenous bradykinin in spontaneously hypertensive rats
      (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Rats were pretreated
      with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L
      NAME), the alpha-adrenergic receptor antagonist phentolamine together with L
      NAME, or phentolamine alone. Sham-injected rats were used as controls. All rats
      subsequently received bradykinin (3, 6, and 30 micrograms/kg i.v.). Bradykinin
      induced a concentration-dependent fall in BP in both WKY and SHR (P < .0005). The
      change in BP was greater in SHR than WKY (P < .0001). BP before bradykinin
      administration was elevated in the L-NAME group in both strains. In WKY, L-NAME
      or L-NAME plus phentolamine did not alter the delta BP concentration-response
      curve to bradykinin (P = NS), whereas in SHR, the delta BP concentration-response
      curve was attenuated (P < .0048). The attenuation was observed for the two lower
      bradykinin doses (P < .0005) but not the highest. In SHR, phentolamine alone
      reduced BP before bradykinin to the same level as in WKY controls, and its delta
      BP concentration-response curve was not different from that of the normotensive
      controls or L-NAME and L-NAME plus phentolamine SHR groups. No difference was
      observed in the duration of the hypotensive response in SHR compared with WKY.
      The present results confirm that in normotensive rats, the hypotensive effect of
      bradykinin was mediated by an unknown mechanism other than through the release of
      nitric oxide. However, in SHR, this mechanism was amplified by additional
      activation of nitric oxide synthesis. This bradykinin-activated nitric oxide
      production may be a pressure-induced mechanism to counteract the hypertensive
      condition.

PMID- 9039081
TI  - Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney.
AB  - The vasopressin receptor subtype that causes nitric oxide (NO) release remains
      controversial. To elucidate this receptor-ligand interaction, we examined the
      effects of vasopressin receptor antagonists on vasopressin-induced release of NO
      from isolated perfused rat kidneys by using a sensitive chemiluminescence assay.
      Vasopressin increased renal perfusion pressure and NO signals in the perfusate in
      a dose-dependent manner. N omega-Monomethyl-L-arginine abolished this increase in
      NO release; however, a similar increase in renal perfusion pressure induced by
      prostaglandin F2 alpha was not associated with the increase in NO release. OPC
      21268, a V1 receptor antagonist, significantly reduced the vasopressin-evoked
      renal vasoconstriction and NO release, whereas OPC-31260, a V2 receptor
      antagonist, had no effects. Moreover, desmopressin, a selective V2 receptor
      agonist, did not increase the NO signal. NO release by vasopressin was markedly
      attenuated in deoxycorticosterone acetate (DOCA)-salt hypertensive rat kidneys
      compared with control kidneys (10(-10) mol/L vasopressin: +0.8 +/- 0.3 versus
      +6.9 +/- 1.4 fmol/min per gram kidney, DOCA versus control; P < .001).
      Histochemical analysis for renal NO synthase revealed a substantial attenuation
      of the staining of endothelial NO synthase in DOCA-salt rats. These results
      directly demonstrate that vasopressin stimulates NO release via the endothelial
      V1 receptor in the rat kidney.

PMID- 9039082
TI  - Endothelin-1 inhibits nitric oxide synthesis in vascular smooth muscle cells.
AB  - We investigated the effects of endothelin-1 on nitric oxide synthesis in vascular
      smooth muscle cells. We measured the production of nitrite, a stable metabolite
      of nitric oxide, and the expression of inducible nitric oxide synthase mRNA and
      protein in cultured rat vascular smooth muscle cells. Incubation of the cultures
      with interleukin-1 beta (10 ng/mL) for 24 hours caused a significant increase in
      nitrite production. Endothelin-1 significantly decreased the interleukin-1 beta
      induced nitrite production by vascular smooth muscle cells in a dose-dependent
      manner (10(-11) to 10(-8) mol/L). Incubation with interleukin-1 beta for 24 hours
      induced expression of inducible nitric oxide synthase mRNA and protein in
      vascular smooth muscle cells, whereas endothelin-1 showed a suppressive effect on
      their expressions. Addition of the endothelin type A receptor antagonist BQ-485,
      but not the endothelin type B receptor antagonist BQ-788, dose-dependently
      inhibited the effect of endothelin-1. After protein kinase C activity was
      functionally depleted by treatment of cells with phorbol 12-myristate 13-acetate
      for 24 hours, the effect of endothelin-1 was abolished. These results indicate
      that endothelin-1 acts on endothelin type A receptors and inhibits nitric oxide
      synthesis in interleukin-1 beta-stimulated vascular smooth muscle cells at least
      partially through a protein kinase C-dependent pathway.

PMID- 9039083
TI  - Urinary endothelin-1 excretion is enhanced by low-dose infusion of brain
      natriuretic peptide in normal humans.
AB  - To evaluate the functional relationship between cardiac natriuretic peptides and
      endothelin-1 within the human kidney, we studied the effects exerted by infusion
      of brain natriuretic peptide on urinary endothelin-1 excretion. We studied twice
      in a single-blind manner five normal volunteers who received a constant infusion
      of 5% dextrose (250 mL/h) or human brain natriuretic peptide-32 at a dose of 4
      pmol/kg per minute. Blood samples were drawn at intervals for measurement of
      hematocrit and concentrations of creatinine, electrolytes, brain natriuretic
      peptide, and endothelin-1. Urine was collected an intervals for measurement of
      flow rate and concentrations of creatinine, sodium, cGMP, and endothelin-1. Blood
      pressure and heart rate were measured every 15 minutes. Placebo administration
      did not change blood pressure, heart rate, or any of the other parameters
      measured in plasma and urine. As expected, brain natriuretic peptide infusion
      caused significant increases in its own plasma levels (basal versus peak levels
      [mean +/- SD], 1.45 +/- 0.20 versus 50.5 +/- 6.0 pmol/L, P < .01), in urinary
      cGMP (0.75 +/- 0.16 versus 1.92 +/- 0.81 fmol/min, P < .05), and in urinary
      sodium excretion (140.0 +/- 38.7 versus 624.2 +/- 181.6 mumol/min, P < .01). In
      addition, it caused an increase in urinary endothelin-1 excretion (4.32 +/- 2.11
      versus 19.67 +/- 9.52 fmol/min, P < .05), without modifying plasma endothelin-1,
      blood pressure, heart rate, creatinine clearance, and urinary flow rate. Our data
      indicate that brain natriuretic peptide, at plasma levels comparable to those
      observed in patients with heart failure, causes a significant increase in urinary
      but not plasma endothelin-1, thus demonstrating a functional link between cardiac
      natriuretic peptides and renal release of endothelin-1.

PMID- 9039084
TI  - Hypoxia stimulates atrial natriuretic peptide gene expression in cultured atrial
      cardiocytes.
AB  - The current study tested the hypothesis that hypoxia stimulates atrial
      natriuretic peptide (ANP) gene expression and secretion in cultured atrial
      myocytes (AT-1 cells). AT-1 cells were obtained from a transplantable mouse
      atrial cardiomyocyte tumor lineage. Confluent AT-1 cells were exposed to hypoxia
      (1% oxygen) or normoxia (21% oxygen) as controls for 6 hours to 7 days. Medium
      ANP levels were measured by radioimmunoassay, and intracellular ANP gene
      transcripts were quantified by Northern and slot blot analyses. Exposure to
      hypoxia resulted in a significant increase in cellular ANP mRNA levels within 36
      hours, which peaked (3.6-fold increase) at 2 days after hypoxic exposure, and
      produced a time-dependent increase in the release of ANP from AT-1 cells for 2 to
      7 days. Transfection studies with recombinant DNA constructs that contained
      fragments of the -3003/+62 sequence of the ANP promoter and the luciferase
      reporter gene revealed that the regulatory sequences that mediate the hypoxia
      induced increase in transcription are located within a region that extends from 
      638 to -518 bp to the transcriptional start site of the ANP gene. Gel mobility
      shift assays demonstrated that hypoxia-inducible nuclear proteins that bound to
      the 120-bp putative hypoxia-responsive elements of the ANP gene were produced
      during hypoxic exposure. We have thus defined a 120-bp region within the ANP gene
      promoter that contains hypoxia-responsive elements that might be responsible for
      the enhancement of ANP gene expression in atrial myocytes during hypoxic
      exposure.

PMID- 9039085
TI  - Thrombin inhibits atrial natriuretic peptide receptor activity in cultured bovine
      endothelial cells.
AB  - Thrombin and the atrial natriuretic peptide (ANP) possess a number of
      functionally antagonistic properties in vascular endothelial cells. Thus,
      regulatory interactions that modulate the activity of one or the other could have
      important sequelae with regard to cardiovascular homeostasis. Thrombin treatment
      effected a dose- and time-dependent reduction in ANP receptor activity (maximal
      70% to 80% inhibition) in cultured bovine aortic endothelial cells. This resulted
      from a decrease in total receptor number as well as a modest reduction in the
      affinity of the receptor for its ligand. The inhibition was largely confined to
      the type C receptor population, in that thrombin had no effect on maximal type A
      receptor-linked cGMP accumulation. The protein kinase C-activating phorbol ester
      12-O-tetradecanoylphorbol 13-acetate effected a similar reduction in binding
      activity; however, suppression of protein kinase C activity did not reverse the
      thrombin effect. Pretreatment of endothelial cells with cycloheximide did not
      completely prevent the thrombin-dependent inhibition, and thrombin did not effect
      a reduction in type C receptor mRNA levels, findings that argue for a
      postsynthetic inhibitory locus. The inhibition of receptor activity was
      effectively irreversible in that suspension of protein synthesis blocked the
      recovery of receptor density on the cell surface. Reduction in type C receptor
      density was accompanied by modest increases in the stability of ANP in the
      culture medium and enhancement of the cellular cGMP response to the peptide,
      particularly at low ligand concentrations. These findings demonstrate a
      potentially important interaction between these two agonist systems in regulating
      endothelial cell function within the vascular wall.

PMID- 9039086
TI  - Neonatal angiotensin-converting enzyme inhibition in the rat induces persistent
      abnormalities in renal function and histology.
AB  - Recently, we reported that neonatal blockade of the renin-angiotensin system in
      the rat produces irreversible abnormalities in renal histology associated with
      increased diuresis. In the present study, we assessed the long-term consequences
      of neonatal angiotensin-converting enzyme inhibition on renal function. Rats were
      injected with 10 mg.kg-1.d-1 enalapril or vehicle from day 3 to day 24 after
      birth. Urine concentrating ability, renal function, and renal histology were
      assessed in 16-week-old rats. There was a twofold increase in diuresis and water
      intake in enalapril-treated rats throughout the study course. Urine osmolality
      after 24 hours of water deprivation was 1008 +/- 108 and 2549 +/- 48 mOsm.kg-1 (P
      < .05) in enalapril- and vehicle-treated rats, respectively. Glomerular
      filtration rate (0.54 +/- 0.03 versus 0.75 +/- 0.06 mL.min-1x100 g body wt-1, P <
      .05) and effective renal plasma flow (1.76 +/- 0.09 versus 2.19 +/- 0.14 mL.min
      1x100 g body wt-1, P < .05) were reduced in neonatally enalapril-treated versus
      control rats. Absolute and fractional urinary sodium excretion values were
      elevated (P < .05) in enalapril-treated rats. Semiquantitative assessment of
      renal histology demonstrated statistically significant degrees of papillary
      atrophy, interstitial fibrosis and inflammation, tubular atrophy and dilatation,
      and focal glomerulosclerosis in neonatally enalapril-treated rats. In conclusion,
      neonatal angiotensin-converting enzyme inhibition in the rat produces
      irreversible alterations in renal function and morphology, demonstrating the
      importance of an intact renin-angiotensin system neonatally for normal renal
      development.

PMID- 9039087
TI  - Vascular angiotensin-converting enzyme expression regulates local angiotensin II.
AB  - We tested the hypothesis that changes in angiotensin-converting enzyme (ACE) gene
      expression can regulate the rate of local vascular angiotensin II (Ang II)
      production. We perfused isolated rat hindlimbs with an artificial medium and
      infused renin and Ang I via the perfusate. Ang I and II were measured by
      radioimmunoassay. We then increased ACE gene expression and ACE levels in the rat
      aorta by producing two-kidney, one clip (2K1C) hypertension for 4 weeks. Gene
      expression was measured by RNAse protection assay, and ACE activity in the vessel
      wall was measured by the Cushman-Cheung assay. Angiotensin I infusion at 1, 10,
      100, and 1000 pmol/mL led to 371 +/- 14 (+/-SEM), 3611 +/- 202, 44,828 +/- 1425,
      and 431,503 +/- 16,439 fmol/mL Ang II released, respectively, from the hindlimbs
      (r = .98, P < .001). Thus, the conversion rate did not change across four orders
      of magnitude, and the system was not saturable under these conditions. In 2K1C
      hindlimbs, Ang I infusion (0.5 pmol/mL) resulted in increased Ang II generation
      (157 +/- 16 versus 123 +/- 23 fmol/mL, P = .014 at minute 10) compared with
      controls. ACE gene expression and ACE activity were increased in 2K1C hindlimbs
      compared with controls (36 +/- 4 versus 17 +/- 1 mU/mg protein, P < .001). Ang II
      degradation in the two groups did not differ. To investigate the conversion of
      locally generated Ang I, we infused porcine renin (0.5 milliunits per mL) into
      2K1C and control hindlimbs. Despite markedly higher Ang I release in sham
      operated than in 2K1C rats (71 +/- 8 versus 37 +/- 6 pmol/mL, P = .008 at minute
      12), Ang II was only moderately increased (36 +/- 3 versus 25 +/- 6 pmol/mL, P =
      .12 at minute 12). This difference between 2K1C rats and controls reflected a
      higher rate of conversion in 2K1C rats. Thus, Ang I conversion in the rat
      hindlimb is linear over a wide range of substrate concentrations and occurs at a
      fixed relationship. Nevertheless, increased ACE gene expression and ACE activity
      in the vessel wall lead to an increase in the conversion of Ang I to Ang II. We
      conclude that local ACE gene expression and ACE activity can influence the local
      rate of Ang II production.

PMID- 9039088
TI  - Pressor effects of endogenous opioid system during acute episodes of blood
      pressure increases in hypertensive patients.
AB  - To investigate the involvement of endogenous opioids in acute increases in blood
      pressure and their functional relationship with atrial natriuretic factor and
      endothelin-1, we assessed plasma levels of beta-endorphin, met-enkephalin,
      dynorphin B, catecholamines, atrial natriuretic factor, and endothelin-1 before
      and after administration of the opioid antagonist naloxone hydrochloride (8 mg
      i.v.) in 28 hypertensive patients with a stress-induced acute increase in blood
      pressure. Ten patients with established mild or moderate essential hypertension
      and 10 normotensive subjects served as control groups. Opioids, atrial
      natriuretic factor, and endothelin-I were radioimmunoassayed after
      chromatographic preextraction; catecholamines were determined by high-performance
      liquid chromatography with electrochemical detection. Patients with an acute
      increase in blood pressure (systolic, 203.2 +/- 2.2 mm Hg; diastolic, 108.4 +/-
      1.3) had plasma opioid, catecholamine, and atrial natriuretic factor levels
      significantly (P < .01) higher than hypertensive control patients (systolic
      pressure, 176.4 +/- 1.0 mm Hg; diastolic, 100.0 +/- 1.4), who had a hormonal
      pattern similar to that of normotensive subjects (systolic pressure, 123.2 +/-
      1.5 mm Hg; diastolic, 75.0 +/- 2.0). Endothelin-1 did not differ in any group. In
      patients with an acute increase in blood pressure, naloxone significantly (P <
      .01) reduced blood pressure, heart rate, opioids, catecholamines, and atrial
      natriuretic factor 10 minutes after administration. Naloxone effects on blood
      pressure, heart rate, opioids, and catecholamines wore off within 20 minutes. In
      control groups, naloxone failed to modify any of the considered parameters. Our
      findings suggest that pressor effects of opioid peptides mediated by the
      autonomic nervous system during stress-induced acute episodes of blood pressure
      increase in hypertensive patients.

PMID- 9039089
TI  - Essential hypertension is associated with decreased insulin clearance and insulin
      resistance.
AB  - Essential hypertension is associated with multiple metabolic abnormalities, among
      them, hyperinsulinemia. This hyperinsulinemia is attributed to the presence of
      decreased insulin sensitivity (insulin resistance) with consequent compensatory
      insulin secretion. We tested the hypothesis that decreased insulin clearance is
      present in hypertensive subjects and contributes to hyperinsulinemia
      independently of the degree of insulin resistance. Seventy-five subjects were
      studied (48 hypertensive and 27 normotensive). Both groups were comparable in
      terms of age, body fat content, waist-to-hip ratio, and sex distribution. A
      primed continuous insulin infusion at 40 mU/m2 per minute was performed. Glucose
      was maintained at baseline levels with the euglycemic clamp technique.
      Hypertensive subjects were characterized by decreased insulin sensitivity
      (insulin-mediated glucose uptake: 5.14 +/- 0.28 versus 7.26 +/- 0.61 mg
      glucose/kg fat-free mass per minute, hypertensive versus normotensive, P = .002),
      increased insulin levels during the insulin infusions (804 +/- 36 versus 510 +/-
      38 pmol/L, hypertensive versus normotensive, P < .001), and decreased insulin
      metabolic clearance rate (328 +/- 15 versus 521 +/- 30 mL/min per meter squared,
      hypertensive versus normotensive, P < .001). In an ANCOVA (including sex, degree
      of obesity, waist-to-hip ratio, and insulin sensitivity as covariates) the
      differences in insulin metabolic clearance rate between normotensive and
      hypertensive subjects remained highly significant (P < .001). Insulin metabolic
      clearance rate was significantly associated with fasting insulin levels. We
      conclude that essential hypertension is independently associated with decreased
      insulin metabolic clearance rate in addition to insulin resistance. A low insulin
      metabolic clearance rate may be a contributory factor to the hyperinsulinemia
      observed in essential hypertension.

PMID- 9039090
TI  - Differential human renal tubular responses to dopamine type 1 receptor
      stimulation are determined by blood pressure status.
AB  - We performed the present studies to determine whether a proximal renal tubular
      dopamine D1-like receptor defect exists in human essential hypertension. Twenty
      four subjects were studied (13 normotensive and 11 hypertensive) in a randomized,
      double-blind, vehicle-controlled study using fenoldopam, a selective D1-like
      receptor agonist. Subjects were studied in sodium metabolic balance at 300 mEq/d,
      after which the salt sensitivity of their blood pressure was determined.
      Fenoldopam at peak doses of 0.1 to 0.2 microgram/kg per minute decreased mean
      arterial pressure in hypertensive subjects but did not change mean pressure in
      normotensive subjects. Fenoldopam increased renal plasma flow to a greater extent
      in hypertensive than normotensive subjects. Fenoldopam increased both urinary and
      fractional sodium excretions in the hypertensive and normotensive groups. In
      normotensive but not hypertensive subjects, fenoldopam increased the fractional
      excretion of lithium and distal sodium delivery. In contrast, both distal
      fractional sodium reabsorption and sodium-potassium exchange fell significantly
      in hypertensive subjects. We conclude that human essential hypertension is
      associated with a reduction in the proximal tubular response to D1-like receptor
      stimulation compared with normotensive subjects. Hypertensive subjects appear to
      have a compensatory upregulation of renal vascular and distal tubular D1-like
      receptor function that offsets the proximal tubular defect, resulting in an
      enhanced natriuretic response to D1-like receptor stimulation.

PMID- 9039091
TI  - Induction of growth hormone receptor and insulin-like growth factor-I mRNA in
      aorta and caval vein during hemodynamic challenge.
AB  - Induction of two-kidney, one clip hypertension (renal hypertension) is
      characterized by a slow increase in left ventricular tension and aortic wall
      stress, as opposed to aortocaval fistula or shunt volume overload, which induces
      a marked and rapid onset of wall stress in the caval vein and right ventricle. In
      the present study, we applied hemodynamic challenge to study the growth response
      involving gene expression of insulin-like growth factor-I (IGF-I) and growth
      hormone receptor (GH-R) mRNA in aorta and caval vein. Volume overload and
      pressure overload were induced in Wistar rats by means of shunt and renal
      hypertension, respectively. Systolic pressure was measured before excision of the
      great vessels, which was performed between 2 and 12 days postoperatively. Aortic
      and caval vein IGF-I and GH-R mRNA expressions were measured by means of a
      solution hybridization assay, and the caval vein was analyzed for IGF-I protein
      by immunohistochemistry. In the volume-distended but not pressurized caval vein
      in shunt rats, verified by telemetry recordings, there was an eightfold increase
      in IGF-I and 3.5-fold increase in GH-R mRNA at day 4 versus control. The IGF-I
      protein appeared to be localized in smooth muscle cells. In the aorta of the
      renal hypertension group, changes were of a slower onset. At day 7, there was a
      fourfold increase in IGF-I and five-fold increase of GH-R mRNA expressions versus
      sham-operated rats. Both the shunt caval vein and renal hypertension aorta showed
      evidence of a structural adaptation of the growth response. The present study
      suggests that acute elevation in vascular wall stress is an important triggering
      factor for overexpression of IGF-I and GH-R mRNA in great vessels. The growth
      hormone/insulin-like growth factor axis may be an important link in mediating
      structurally adaptive growth responses in the blood vessel wall.

PMID- 9039092
TI  - Role of the alpha-, beta-, and gamma-subunits of epithelial sodium channel in a
      model of polygenic hypertension.
AB  - The pathophysiological basis of Liddle's syndrome, a rare autosomal dominant form
      of arterial hypertension, has been found to rest on missense mutations or
      truncations of the beta- and gamma-subunits of the epithelial sodium channel. The
      hypothesis has been advanced that molecular variants of these genes might also
      contribute to the common polygenic forms of hypertension. We tested this
      hypothesis by performing a cosegregation study in a reciprocal cross between the
      stroke-prone spontaneously hypertensive rat (SHRSPHD) and a Wistar-Kyoto rat (WKY
      1HD) reference strain. We carried out genetic mapping and chromosomal assignment
      of the alpha-, beta-, and gamma-subunits of the epithelial sodium channel using
      both linkage analysis and fluorescent in situ hybridization techniques. We
      demonstrate that in the rat, the beta- and gamma-subunits, as in humans, are in
      close linkage; they map to rat chromosome 1 and cosegregate with systolic
      pressure after dietary NaCl (logarithm of the odds [LOD] score, 3.7), although
      the peak LOD score of 5.0 for this quantitative trait locus was detected 4.4 cM
      away from the beta-/gamma-subunit locus. The alpha-subunit was mapped to
      chromosome 4 and exhibited no linkage to blood pressure phenotype. Comparative
      analysis of the complete coding sequences of all three subunits in the SHRSPHD
      and WKY-1HD strains revealed no biologically relevant mutations. Furthermore,
      Northern blot comparison of mRNA levels for all three subunits in the kidney
      showed no differences between SHRSPHD and WKY-1HD. Our results fail to support a
      material contribution of the epithelial sodium channel genes to blood pressure
      regulation in this model of polygenic hypertension.

PMID- 9039093
TI  - Region-specific neuropeptide Y overflows at rest and during sympathetic
      activation in humans.
AB  - Neuropeptide Y coexists with norepinephrine in sympathetic nerves and is
      coreleased into the circulation on sympathetic activation. Little is known about
      the regional release of neuropeptide Y in humans under normal conditions or in
      pathophysiological situations of sympathetic activation or denervation. We
      measured plasma neuropeptide Y-like immunoreactivity and norepinephrine
      concentrations in samples taken from the brachial artery; coronary sinus; and
      internal jugular, antecubital, or hepatic veins in volunteers aged 20 to 64
      years. Regional neuropeptide Y overflow at rest was calculated from venoarterial
      plasma concentration differences and plasma flow, and norepinephrine spillover
      was determined by [3H]norepinephrine infusion techniques. Cardiac release of
      neuropeptide Y and norepinephrine was examined in response to various stressors
      as well as in clinical models of sympathetic activation, cardiac failure, and
      denervation after cardiac transplantation. In healthy volunteers, cardiac,
      forearm, and jugular venous sample neuropeptide Y concentrations were similar to
      arterial levels. Hepatic vein plasma neuropeptide Y was greater than arterial
      both at rest (119 +/- 5% of arterial, n = 7) and after a meal (132 +/- 12%, n =
      7), with neuropeptide Y overflows of 6 +/- 2 and 11 +/- 2 pmol/min, respectively.
      In contrast, hepatomesenteric norepinephrine spillover was not significantly
      increased by feeding. Although coronary sinus plasma norepinephrine
      concentrations increased significantly with the cardiac sympathetic activation
      accompanying mental arithmetic, coffee drinking, isotonic exercise, and bicycle
      exercise, only the latter powerful sympathetic stimulus increased neuropeptide Y
      overflow. Cardiac failure was associated with increased resting release of both
      norepinephrine and neuropeptide Y from the heart, whereas postcardiac transplant
      norepinephrine spillover from the heart was reduced. The net overflow of
      neuropeptide Y to plasma observed at rest across the hepatic circulation, but not
      the cardiac, forearm, or cerebral circulations, indicates that the gut, the
      liver, or both make a major contribution to systemic plasma neuropeptide Y levels
      in humans. Sympathetic activation by exercise produced a modest increase in
      cardiac neuropeptide Y overflow but to only approximately 25% of the resting
      input from the gut and without a change in arterial neuropeptide Y concentration.
      Plasma neuropeptide Y measurements are less sensitive than those of plasma
      norepinephrine concentrations as an index for quantifying sympathetic neural
      responses regulating the systemic circulation.

PMID- 9039094
TI  - Genetically complex cardiovascular traits. Origins, problems, and potential
      solutions.
AB  - Modern molecular genetic analysis tools are making it possible for researchers to
      investigate, and in many cases actually disclose, mutations and other genetic
      factors that contribute to disease susceptibility. However, the ease with which
      these factors can be identified is dictated by not only the number of factors
      underlying or influencing the trait, but also by the manner in which these
      factors interact. Traits that are influenced by multiple genetic and nongenetic
      factors are termed "complex" genetic traits and are receiving a great deal of
      attention in the current medical literature. Hypertension and blood pressure
      regulation are considered paradigmatic complex traits. In this paper, the origin,
      nature, and dilemmas associated with the analysis of complex traits are
      considered. Basic biochemical and physiological determinants of blood pressure
      are described in an effort to show how genetic complexity could arise within an
      individual, and fundamental concepts in population genetics and evolutionary
      theory are discussed to expose the reasons certain forms of genetic complexity
      can emerge and be sustained in the population at large. Methods for approaching
      the genetic dissection of complex traits and diseases are also enumerated, with
      simple descriptions of the scientific motivation offered for each. Problems
      plaguing these approaches are also discussed. Finally, areas for future research
      are outlined with the hope of sparking further debate on the subject.

PMID- 9039095
TI  - Angiotensin-converting enzyme gene mutations, blood pressures, and cardiovascular
      homeostasis.
AB  - A common polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE in
      humans, Ace in mice) is associated with differences in circulating ACE levels
      that may confer a differential risk for cardiovascular diseases. To study the
      effects of genetically determined changes in Ace gene function within a defined
      genetic and environmental background, we have studied mice having one, two, or
      three functional copies of the Ace gene at its normal chromosomal location. ACE
      activities in the serum increased progressively from 62% of normal in the one
      copy animals to 144% of normal in the three-copy animals (P < 10(-15), n = 132).
      The blood pressures of the mice having from one to three copies of the Ace gene
      did not differ significantly, but the heart rates, heart weights, and renal
      tubulointerstitial volumes decreased significantly with increasing Ace gene copy
      number. The level of kidney renin mRNA in the one-copy mice was increased to 129
      +/- 9% relative to that of the normal two-copy mice (100 +/- 4%, P = .01, n =
      16). We conclude that significant homeostatic adaptations successfully normalize
      the blood pressures of mice that have quantitative changes in Ace gene function.
      Our results suggest only that quantitative changes in expression of the Ace gene
      will observably affect blood pressures when accompanied by additional
      environmental or genetic factors that together with Ace exceed the capacity of
      the homeostatic mechanisms.

PMID- 9039096
TI  - Linkage analysis using platelet-activating factor Ca2+ response in transformed
      lymphoblasts.
AB  - Epstein-Barr virus-transformed lymphoblasts from patients with essential
      hypertension demonstrate enhanced G protein-mediated cytosolic free calcium
      ([Ca2+]i) response to platelet-activating factor (PAF). To map genes responsible
      for variation in G protein-coupled signaling, we used this cellular phenotype for
      a linkage study of transformed cell lines from the Centre d'Etude du
      Polymorphisme Humain (CEPH) reference pedigrees. The PAF-evoked change in [Ca2+]i
      ranged from 20 to 392 mmol/L and was highly reproducible within each cell line.
      PAF-elicited [Ca2+]i responses were obtained in lymphoblastic cell lines from
      five densely mapped pedigrees of the CEPH collection. Using PAF-evoked [Ca2+]i
      responses as a quantitative trait, two-point sibpair linkage analyses were
      conducted using 5150 markers from the Collaborative Human Linkage Center (CHLC)
      database. Nine loci, located on chromosomes 1, 4, 10, 11, 13, 16, and 17, were
      suggestive of linkage, with values of P < 7.4 x 10(-4). Multipoint linkage
      analysis produced a significant linkage finding (P = 2.1 x 10(-5) in one family
      at D16S151, with suggestive linkage results for seven additional markers spanning
      a 40-cM interval of chromosome 16. Multipoint analysis produced suggestive
      findings of linkage to eight loci from two distinct regions of chromosome 11 in
      another family. These results indicate that loci involved in the control of G
      protein-mediated mechanisms, suggested to be involved in the pathophysiology of
      essential hypertension, can be identified using cell lines from general pedigrees
      selected without any knowledge of the blood pressure status of the donors. This
      strategy represents an approach to rapidly and inexpensively mapping loci related
      to common, complex disorders, using phenotypes that are stable in immortalized
      lymphoblasts together with existing reference pedigree cell lines and genotype
      databases.

PMID- 9039097
TI  - Angiotensin-converting enzyme and angiotensinogen gene polymorphisms, plasma
      levels, cardiac dimensions. A twin study.
AB  - We tested the hypotheses that angiotensin-converting enzyme insertion/deletion
      (I/D) and angiotensinogen 235 methionine/threonine (M/T) substitution gene
      polymorphisms influence angiotensin-converting enzyme and angiotensiongen serum
      concentrations and cardiac dimensions in 91 monozygotic and 41 dizygotic twin
      pairs. Cardiac dimensions were determined echocardiographically. Angiotensin
      converting enzyme levels were 24 +/- 11, 43 +/- 18, and 58 +/- 24 U/L for the II,
      ID, and DD genotypes, respectively (P < .01). Posterior wall thickness was 8.1 +/
      1.3, 8.6 +/- 1.7, and 8.9 +/- 1.9 mm for these genotypes (P < .05). Angiotensin
      converting enzyme levels were correlated with posterior wall thickness (r = .15,
      P < .05). The intrapair differences in angiotensin converting enzyme levels for
      monozygotic, concordant dizygotic, and discordant dizygotic twins were 1.36 +/-
      1.6, 1.86 +/- 1.6, and 17.25 +/- 4.3 U/L, respectively. The angiotensinogen M/T
      genotypes exerted no influence on cardiac dimensions or on angiotensinogen
      concentrations. The additive genetic effect on angiotensin-converting enzyme
      levels (0.49), on posterior wall thickness (0.26), and on septum thickness (0.37)
      was significant (P < .01), although shared and nonshared environmental effects
      were also identified. Our data confirm the impressive effect that the angiotensin
      converting enzyme D allele exerts on angiotensin-converting enzyme plasma levels.
      Furthermore, our data also suggest that the angiotensin-converting enzyme gene
      locus is primarily responsible for angiotensin-converting enzyme plasma levels.
      Our twin study also indicates that the angiotensin-converting enzyme gene locus
      is genetically linked to posterior wall thickness. The correlation between
      angiotensin-converting enzyme levels and posterior wall thickness suggests that
      this effect is exerted by angiotensin-converting enzyme. We were unable to
      demonstrate genetic linkage between the angiotensinogen gene locus and cardiac
      dimensions in this study.

PMID- 9039099
TI  - Antisense inhibition and adeno-associated viral vector delivery for reducing
      hypertension.
AB  - Antisense oligodeoxynucleotides have been designed to inhibit the production of
      specific proteins. In models of hypertension, we have targeted the renin
      angiotensin system at the level of synthesis (angiotensinogen) and the receptor
      (AT1 receptor). The design of antisense oligonucleotides requires choosing a site
      to inhibit mRNA processig or translation. The strategy we use is to make three
      oligonucleotides of antisense sequences, upstream and downstream from the AUG
      site and over the AUG site. The oligonucleotides are tested in a screening test.
      Antisense oligonucleotides to AT1-receptor mRNA and to angiotensinogen mRNA
      reduce blood pressure in spontaneously hypertensive rats when injected into the
      brain. They significantly reduce the concentration of the appropriate protein.
      The oligonucleotides are also effective when administered systemically. The
      decrease in blood pressure with antisense oligonucleotides delivered in blood or
      brain lasts 3 to 7 days. To prolong the action, direct injection of naked DNA and
      injection of DNA in liposome carriers have been tested. Viral vectors have been
      developed to deliver antisense DNA. The viral vectors available include
      retroviruses and adenovirus, but the adeno-associated virus (AAV) vector is the
      vector of choice for ultimate use in gene therapy. It offers safety because it is
      nonpathogenic, has longevity because it integrates into the genome, and has
      sufficient carrying capacity to carry up to 4.5 kb antisense or gene in a
      recombinant AAV. Using rAAV-antisense to AT1 mRNA, there is efficient
      transfection into cells and an inhibition of AT1 receptor number. In in vivo
      tests, rAAV-AS AT1-receptor when injected into the brains of SHR reduces blood
      pressure for more than 2 months. In young rats (3 weeks old), rAAV-AS AT1
      receptor decreases blood pressure and slows the development of hypertension.
      While further experiments need to be done on dose-response relationships and on
      the cellular mechanisms of these effects, the results show the feasibility of AAV
      as a vector for antisense inhibition, which may ultimately be used in gene
      therapy for hypertension.

PMID- 9039098
TI  - Aging, acculturation, salt intake, and hypertension in the Kuna of Panama.
AB  - The indigenous Kuna who live on islands in the Panamanian Caribbean were among
      the first communities described with little age-related rise in blood pressure or
      hypertension. Our goals in this study were to ascertain whether isolated island
      dwelling Kuna continue to show this pattern, whether migration to Panama City and
      its environs changed the patterns, and whether the island-dwelling Kuna have
      maintained their normal blood pressure levels despite partial acculturation,
      reflected in an increased salt intake. We enrolled 316 Kuna participants who
      ranged in age from 18 to 82 years. In 50, homogeneity was confirmed by
      documentation of an O+ blood group. In 92 island dwellers, diastolic hypertension
      was not identified and blood pressure levels were as low in volunteers over 60
      years of age as in those between 20 and 30 years of age. In Panama City,
      conversely, hypertension prevalence was 10.7% and exceeded 45% in those over 60
      years of age (P < .01), blood pressure levels were higher in the elderly, and
      there was a statistically significant positive relationship between age and blood
      pressure (P < .01). In Kuna Nega, a Panama City suburb designed to maintain a
      traditional Kuna lifestyle but with access to the city, all findings were
      intermediate. Sodium intake and excretion assessed in 50 island-dwelling Kuna
      averaged 135 +/- 15 mEq/g creatinine per 24 hours, exceeding substantially other
      communities free of hypertension and an age-related rise in blood pressure.
      Despite partial acculturation, the island-dwelling Kuna Indians are protected
      from hypertension and thus provide an attractive population for examining
      alternative mechanisms.

PMID- 9039100
TI  - Arthus C. Corcoran Memorial Lecture. Influence of nitric oxide and angiotensin II
      on renal involvement in hypertension.
AB  - Remarkable advances have been made with prolonged antihypertensive therapy in
      reversing cardiovascular morbidity and mortality. Deaths from stroke have been
      reduced by 70% and from coronary heart disease by 35%. In contrast, endstage
      renal disease resulting from hypertension continues to increase. The explanations
      for this seeming paradox remain unresolved even though experimental models have
      demonstrated that certain antihypertensive agents may have beneficial renal and
      intrarenal hemodynamic effects; but reversal of the intrarenal pathological
      lesions have not been shown to improve. This discussion summarizes recent studies
      from our laboratory in aged (73- and 85-week-old) spontaneously hypertensive rats
      (SHR) with naturally occurring end-stage renal disease and in a model of aged SHR
      employing nitric oxide inhibition in younger, adult (20-week-old) SHR. Our
      findings demonstrated that the systemic and whole renal hemodynamics, intrarenal
      glomerular dynamics, proteinuria, and renal pathological lesions can be prevented
      or reversed with angiotensin-converting enzyme inhibition therapy but not with
      hydrochlorothiazide (at similar levels of arterial pressure reduction). The
      implications and possible mechanisms involved in the development of both
      naturally occurring and nitric oxide-exacerbated SHR are multifactorial,
      involving the endothelial nitric oxide system and its interaction with
      angiotensin II (and possibly bradykinin) among other factors. Moreover, these
      pathophysiological cellular mechanisms may be shared by the aging process as well
      as in naturally occurring spontaneous hypertension in the rat and, perhaps, in
      humans with essential hypertension. Thus, antihypertensive therapy seems to be
      specific in its ability to prevent and even reverse the pathophysiological
      derangements of renal involvement in hypertension. Thus, prevention and reversal
      of end-stage renal disease do not seem to require greater reduction of arterial
      pressure than with other target-organ involvement. However, they do require
      specific inhibition of the arteriolar and glomerular lesions produced by the
      disease.

PMID- 9039101
TI  - Nitric oxide in renal cortex and medulla. An in vivo microdialysis study.
AB  - This study examined the production of nitric oxide (NO) in the renal cortex and
      medulla through the use of an in vivo microdialysis technique. Oxyhemoglobin
      (OxyHb) at a concentration of 3 mumol/L was perfused through the dialysis system
      to trap tissue NO. Methemoglobin (MetHb), which was formed by NO oxidation of
      OxyHb in the dialysate, was spectrophotometrically assayed at 401 nm. Because the
      oxidation of OxyHb to produce MetHb is stoichiometric with NO, the production of
      NO can be determined by the rate of MetHb formation. We found that NO
      concentration was significantly higher (P < .05) in the medulla (57.1 +/- 5.57
      nmol/L, n = 10) than in the cortex (31.2 +/- 5.7 nmol/L, n = 9). The minimal
      detectable NO level of this assay is approximately 10 nmol/L. Intravenous
      infusion of L-arginine (3 mg/kg per minute) for 30 minutes produced a twofold to
      three fold increase in cortical and medullary NO; NG-nitro-L-arginine methyl
      ester (L-NAME) (10 micrograms/kg per minute) decreased NO by 33% in the renal
      cortex and by 46.5% in the renal medulla. We have also compared under the same
      conditions the degradation products of NO, nitrite, and nitrate in the renal
      cortex and medulla using in vivo microdialysis combined with microtiter plate
      colorimetry. Nitrite/nitrate concentration was significantly higher (P < .05) in
      the medulla (2.7 +/- 0.6 mumol/L, n = 4) than in the cortex (2.1 +/- 0.2 mumol/L,
      n = 4). Infusion of L-arginine increased cortical and medullary nitrite/nitrate
      by 65% and 39%, respectively. L-NAME reduced cortical and medullary
      nitrite/nitrate by 18% and 23%, respectively. The results indicate that the OxyHb
      NO microdialysis trapping technique is a highly sensitive in situ method for
      detecting regional tissue NO concentration and changes in the NO synthase
      activity in the kidney. These studies have shown that NO concentration is higher
      in medullary tissue than in the cortex.

PMID- 9039102
TI  - Temporal influence of the renal nerves on renal excretory function during chronic
      inhibition of nitric oxide synthesis.
AB  - To determine whether the sympathetic nervous system contributes to the
      hypertension induced by long-term suppression of nitric oxide synthesis, we
      determined the neurally induced changes in renal excretory function during
      chronic administration of NG-nitro-L-arginine methyl ester (L-NAME). Studies were
      carried out in six conscious chronically instrumented dogs subjected to
      unilateral renal denervation and surgical division of the urinary bladder into
      two hemibladders to allow separate 24-hour urine collection from denervated and
      innervated kidneys. Animals were studied during acute (100 minutes) and chronic
      (5 days) intravenous infusion of L-NAME at 37.1 nmol/kg per minute (10
      micrograms/kg per minute). During the first 100 minutes of L-NAME, there were no
      significant changes in mean arterial pressure (control: 96 +/- 3 mm Hg), but
      heart rate fell from 66 +/- 6 to 55 +/- 7 beats per minute. Changes in glomerular
      filtration rate were not significant, but renal plasma flow and urinary sodium
      excretion decreased to approximately 75% and 50% of control values, respectively;
      however, these changes were comparable in both kidneys. In association with these
      responses, plasma concentrations of norepinephrine (control: 887 +/- 130 pmol/L
      or 150 +/- 22 pg/mL) and epinephrine (control: 691 +/- 192 pmol/L or 108 +/- 30
      pg/mL) tended to decrease. In contrast to the acute responses, mean arterial
      pressure increased from 92 +/- 3 to 106 +/- 3 mm Hg and heart rate decreased from
      72 +/- 4 to 57 +/- 5 beats per minute by day 5 of L-NAME infusion, while renal
      plasma flow and glomerular filtration rate were not significantly different from
      control values. Most importantly, there were no significant differences in
      urinary sodium excretion between innervated (control: 31 +/- 2 mmol/d) and
      denervated (control 33 +/- 2 mmol/d) kidneys during chronic L-NAME infusion or
      during the recovery period. These results indicate that the renal sympathetic
      nerves do not play an important role in promoting sodium retention during either
      acute or chronic inhibition of nitric oxide synthesis in conscious dogs. Thus,
      increased renal sympathetic nerve activity does not contribute significantly to L
      NAME-induced hypertension.

PMID- 9039104
TI  - Pressure natriuresis and autoregulation of inner medullary blood flow in canine
      kidney.
AB  - We have evaluated the responses to changes in arterial pressure on regional blood
      flows in the renal medulla and sodium excretion simultaneously in denervated
      kidneys of six anesthetized sodium-replete dogs. Renal regional blood flow
      responses were determined using laser-Doppler needle flow probes and whole-kidney
      blood flow was assessed using an electromagnetic flow probe. The responses to
      stepwise reductions in renal arterial pressure (140 to 70 mm Hg) were examined
      first with a laser-Doppler needle probe inserted in the outer medulla and then
      repeated after advancing the same probe in the inner medulla. There were no
      differences in the control values of total renal blood flow (4.4 +/- 0.7 to 4.5
      +/- 0.5 mL.min-1.g-1), glomerular filtration rate (0.89 +/- 0.7 to 0.94 +/- 0.9
      mL.min-1.g-1), sodium excretion (3.6 +/- 0.6 to 3.4 +/- 0.5 mumol.min-1.g-1), and
      urinary excretion rate of nitric oxide metabolites (nitrate/nitrite, 1.6 +/- 0.2
      to 1.5 +/- 0.2 nmol.min-1.g-1) at the start of both experimental periods. During
      changes in renal arterial pressure, inner medullary blood flow exhibited
      efficient autoregulation similar to that in outer medullary blood flow. Usual
      excretory responses to reductions in renal arterial pressure as well as
      autoregulation of cortical and whole-kidney blood flows and glomerular filtration
      rate were observed in these dogs. The slopes of the relationship between arterial
      pressure and sodium excretion (0.046 +/- 0.007 to 0.044 +/- 0.009 mumol.min-1.g
      1.mm Hg-1) or nitrate/nitrite excretion (0.014 +/- 0.003 to 0.013 +/- 0.003
      nmol.min-1.g-1.mm Hg-1) were similar in both experimental periods. These data
      indicate that blood flow to the inner medulla is efficiently autoregulated as in
      outer medulla and cortex of the kidney in anesthetized dogs and demonstrate
      further that the arterial pressure-induced natriuretic responses do not require
      associated changes in medullary blood flow.

PMID- 9039103
TI  - Role of nitric oxide in modulating the long-term renal and hypertensive actions
      of norepinephrine.
AB  - We have previously reported that nitric oxide (NO) plays an important role in
      protecting the renal vasculature from acute norepinephrine-induced
      vasoconstriction. The purpose of this study was to determine the importance of
      this interaction between NO and norepinephrine in long-term control of renal
      hemodynamics and arterial pressure. To achieve this goal, we examined the effects
      of an intrarenal infusion of norepinephrine (NE) (0.1 microgram.kg-1.min-1) for 7
      days in conscious, chronically instrumented control dogs and in dogs pretreated
      with a synthesis inhibitor, L-NAME (3 micrograms.kg-1.min-1 intrarenally). Both
      groups of dogs also received captopril (15 micrograms.kg-1.min-1) plus
      angiotensin I] intravenously to clamp the renin-angiotensin system throughout the
      protocol. In control dogs (n = 6), intrarenal infusion of NE decreased renal
      plasma flow by 9% (134 +/- 10 to 122 +/- 14 mL/min) and glomerular filtration
      rate by 16% (49 +/- 4 to 41 +/- 5 mL/min) while having no effect on mean arterial
      pressure (100 +/- 3 to 98 +/- 4 mm Hg). In marked contrast, in dogs pretreated
      with intrarenal L-NAME (n = 9), NE decreased renal plasma flow by 37% (129 +/- 8
      to 81 +/- 16 mL/min) and glomerular filtration rate by 32% (47 +/- 3 to 32 +/- 5
      mL/min) while increasing mean arterial pressure from 104 +/- 5 to 113 +/- 6 mm
      Hg. The results of this study demonstrate that NO plays an important role in
      modulating the long-term actions of NE on renal function and arterial pressure.

PMID- 9039105
TI  - Aberrant renal vascular morphology and renin expression in mutant mice lacking
      angiotensin-converting enzyme.
AB  - To determine whether angiotensin-converting enzyme plays a role in the
      development and maintenance of normal renal architecture, the renal morphology of
      10- to 12-month-old female mice homozygous for a disruption of the converting
      enzyme gene was compared with that of age-matched wild-type mice. Tubular
      obstruction, dilatation, and atrophy were present in all kidneys from the
      homozygous mutant mice but absent in wild types; two kidneys from 4 mutant mice
      but none from the wild types were hydronephrotic. The entire arterial vascular
      tree, microdissected from mice with no converting enzyme, was grossly distorted
      in comparison to the vasculature of wild-type mice; all intrarenal arterial
      vessels were widened and thickened, including the terminal (afferent) arterioles.
      In wild-type mice kidneys, renin-positive cells were detected exclusively in a
      juxtaglomerular localization. In contrast, abnormal distribution of renin
      immunostaining was observed in mice without converting enzyme; scattered renin
      positive cells were seen along the arterial vessels, often in a perivascular
      localization, and interstitial renin-positive cells surrounded glomeruli. Kidney
      renin mRNA was increased more than 32-fold in the mutant mice compared with wild
      types. Northern blot analysis revealed that this increase included the
      accumulation of large amounts of smaller renin RNA transcripts. In summary, mice
      lacking the converting enzyme exhibit abnormal renal vessels and tubules. Renin
      synthesis is increased, accompanied by the presence of small renin mRNA species,
      and renin is present mainly in interstitial and perivascular cells. We conclude
      that angiotensin-converting enzyme is necessary to preserve normal kidney
      architecture and the normal pattern of renin expression.

PMID- 9039107
TI  - Intrarenal dopamine production and distribution in the rat. Physiological control
      of sodium excretion.
AB  - Dopamine (DA), produced by the renal proximal tubule, has been demonstrated as an
      intrarenal paracrine hormone mediating diuresis and natriuresis. The precise
      mechanism by which DA exerts its cell-to-cell action is not fully understood. In
      the present study, renal interstitial fluid (RIF) DA (by in vivo microdialysis)
      and urinary DA excretion (UDAV) were compared in anesthetized rats on either
      normal (0.28% NaCI, NS) or high (4.0% NaCI, HS) sodium balance and in response to
      acute gamma-L-glutamyl-L-dopa (gludopa) administration. Urine flow (UV) and
      sodium excretion (UNaV) in HS were greater than in NS rats. UDAV was increased in
      HS compared with NS rats. RIF DA was significantly lower in HS than NS rats.
      Gludopa at 3, 5, and 7.5 nmol/kg (IV bolus) produced a larger increase in UDAV
      than RIF DA. Only the highest dose of gludopa (7.5 nmol/kg), which resulted in a
      7.3-fold increase in UDAV and 1.7-fold increase in RIF DA, was associated with
      significant diuresis and natriuresis. Cortical and medullary blood flow remained
      unchanged after gludopa (7.5 nmol/kg) administration, while angiotensin II (100
      ng.kg-1.min-1) induced significant reduction in cortical and medullary blood
      flow. Prior bilateral renal denervation did not have a significant effect on
      basal DA levels (RIF DA and UDAV) or gludopa-induced DA production or natriuresis
      and diuresis. These data demonstrated that both chronic sodium loading and acute
      gludopa administration stimulated renal DA production and release predominantly
      into the tubule lumen, where DA had a direct tubule action in the control of
      UNaV. Renal DA production and its renal effects were not significantly regulated
      by renal sympathetic nerve activity.

PMID- 9039106
TI  - Afferent and efferent arteriolar vasoconstriction to angiotensin II and
      norepinephrine involves release of Ca2+ from intracellular stores.
AB  - Renal vascular responses to angiotensin II (Ang II) and norepinephrine (NE) are
      reported to involve both mobilization of calcium from intracellular stores and
      activation of calcium influx pathways. The present study was conducted to
      determine the contribution of calcium release from intracellular stores to
      afferent and efferent arteriolar responses to Ang II and NE. Experiments were
      performed in vitro using the blood-perfused, juxtamedullary nephron technique
      combined with videomicroscopy. The responses of afferent and efferent arterioles
      to Ang II and NE were determined before and after depletion of intracellular
      calcium pools with 1 mumol/L thapsigargin. Positive control responses were
      obtained with 55 mmol/L KCI. Ang II concentrations of 0.1, 1.0, and 10 nmol/L
      decreased afferent arteriolar diameter by 10 +/- 4%, 17 +/- 4%, and 29 +/- 6%,
      respectively (P < .05; n = 8). NE also decreased afferent diameter by 5 +/- 1%,
      13 +/- 1%, and 57 +/- 9% at concentrations of 10, 100, and 1000 nmol/L,
      respectively (P < .05; n = 6). Thapsigargin treatment shifted the afferent
      arteriolar concentration-response curves for both Ang II and NE significantly to
      the right. Nevertheless, KCI evoked a pronounced vasoconstriction and decreased
      afferent diameter by 56 +/- 7% (P < .05; n = 6). Postglomerular responses to Ang
      II and NE were abolished by thapsigargin. During the control period, efferent
      diameter decreased by 3 +/- 1%, 7 +/- 2%, and 14 +/- 4% for the three Ang II
      concentrations and 3 +/- 1%, 5 +/- 1%, and 15 +/- 4% in response to the three NE
      concentrations, respectively. These responses were completely eliminated in the
      presence of thapsigargin, whereas KCI evoked an efferent arteriolar
      vasoconstriction of 57 +/- 9% (P < .05). These data demonstrate that agonist
      induced calcium release from intracellular stores represents an essential
      component in the afferent and efferent arteriolar response to Ang II and NE.
      Furthermore, they suggest that efferent arteriolar responses to these agents may
      rely more heavily on calcium release from this store, whereas afferent responses
      may include activation of other pathways.

PMID- 9039108
TI  - The link among nitric oxide synthase activity, endothelial function, and aortic
      and ventricular hypertrophy in hypertension.
AB  - The adaptive changes that occur in the left ventricle (LV) and vessels in
      response to hypertension, namely, muscle hypertrophy/hyperplasia, endothelial
      dysfunction, and extracellular matrix increase, do not depend solely on blood
      pressure elevation. These changes are in fact, maladaptive since they are
      forerunners of cardiac failure, stroke, and renal failure. Nitric oxide, an
      endogenous vasodilator and inhibitor of vascular smooth muscle cell growth, is
      synthesized in the endothelium by constitutive nitric oxide synthase (cNOS). We
      investigated the relationships among LV and aortic cNOS activity (conversion of
      [14C] L-arginine to [14C] L-citrulline), with LV hypertrophy (LV weight/body
      weight), and (2) aortic hypertrophy (aortic weight/ length) in spontaneously
      hypertensive rats (SHR) and Dahl salt-sensitive (DS) rats matched for blood
      pressure (219 +/- 12 versus 211 +/- 7 mm Hg, P = NS) and age. Compared with their
      normotensive counterparts, aortic cNOS activity was increased 106% in SHR but
      reduced by 73% in DS rats. The correlation between blood pressure and aortic cNOS
      activity was positive (r = .74, P < .01) in SHR and negative (r = -.82, P < .01)
      in DS rats, LV cNOS activity was increased 73% in SHR compared with normotensive
      Wistar-Kyoto rats (P < .01). On the other hand, LV cNOS activity was not
      increased in hypertensive DS rats compared with normotensive DS rats. In SHR,
      aortic hypertrophy did not increase significantly and LV hypertrophy increased
      only 15%, whereas in hypertensive DS rats the aorta and LV hypertrophied 36% and
      88%, respectively (both P < .01). Moreover, in DS rats there was a negative
      correlation between cNOS activity and aortic hypertrophy (r = -.70, P < .01). In
      DS rats, antihypertensive therapy consisting of an angiotensin-converting enzyme
      inhibitor, perindopril, and a diuretic, indapamide, normalized blood pressure,
      aortic cNOS activity, and LV hypertrophy and reduced aortic hypertrophy. Our
      studies imply that upregulation of vascular cNOS activity has a protective
      cardiovascular homeostatic role in hypertension. Clinically, the variable end
      organ disease observed in individuals with similar severity of hypertension may
      be explained, at least in part, by genetically conditioned differences in
      vascular cNOS activity in response to hypertension.

PMID- 9039109
TI  - Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in
      experimental hypertension.
AB  - NG,NG-dimethyl-L-arginine (ADMA) is an endogenously synthesized nitric oxide (NO)
      synthase inhibitor which has potent pressor/vasoconstrictor effects.
      Dimethylargininase metabolizes ADMA to L-citrulline and plays a key role in
      determining the in vivo levels of ADMA. To investigate the role of ADMA in the
      pathogenesis of hypertension, we measured 24-hour urinary excretion of ADMA
      (UADMA) and nitrate/nitrite (NOx) in Dahl salt-sensitive hypertensive rats and
      spontaneously hypertensive rats (SHR). In Dahl salt-resistant rats, high-salt
      diet (8% NaCl) did not increase blood pressure and increased urinary NOx (P <
      .01) without changes in UADMA compared with low-salt diet (0.3% NaCl). In
      contrast, in Dahl salt-sensitive rats, high-salt diet increased blood pressure (P
      < .01), did not change urinary NOx excretion, and increased UADMA (P < .01).
      There was a significant (r = .65, P < .01) correlation between UADMA and the
      level of blood pressure in Dahl salt-sensitive rats. Plasma levels of NOx and
      ADMA and renal dimethylargininase content were comparable among them. These
      results may suggest that in Dahl salt-resistant rats, blood pressure is kept
      constant during high-salt intake, possibly due to the compensatory increased
      production of NO, and that in Dahl salt-sensitive rats, high-salt intake
      increases the production of ADMA, attenuates the compensatory increases in NO,
      and increases blood pressure. These results also suggest that the systemic
      production of ADMA is not dependent on renal dimethylargininase. SHR had
      significantly greater urinary NOx excretion (P < .05) and smaller UADMA than
      Wistar-Kyoto rats (P < .05), and UADMA was inversely correlated with their mean
      arterial pressure (r =.64, P < .05). In conclusion. ADMA, independently of the
      renal dimethylargininase content, may play a role in the pathogenesis in Dahl
      salt-sensitive hypertensive rats but not in SHR.

PMID- 9039110
TI  - Calcitonin gene-related peptide is a depressor in NG-nitro-L-arginine methyl
      ester-induced hypertension during pregnancy.
AB  - Inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L
      NAME) increases blood pressure and fetal mortality in pregnant rats. We
      previously reported that administration of calcitonin gene-related peptide (CGRP)
      reduces the blood pressure and fetal death produced by L-NAME. To determine the
      hemodynamic role of endogenous CGRP in this setting, CGRP8-37, a CGRP receptor
      antagonist, was used. In addition, CGRP mRNA and peptide levels were determined
      in dorsal root ganglia. L-NAME or control rats had intravenous (for drug
      administration) and arterial (for continuous mean blood pressure monitoring)
      catheters surgically placed and were studied in the conscious unrestrained state.
      Baseline blood pressure was higher in the L-NAME than the control rats on days
      19, 20, and 21 or pregnancy and postpartum day 1. Vehicle administration did not
      change blood pressure in any group, and CGRP8-37 (100 micrograms) did not change
      blood pressure in control groups. However, CGRP8-37 administration to the L-NAME
      rats further increased blood pressure (P < .05) on days 19 (8 +/- 1), 20 (12 +/-
      2), and 21 (7 +/- 1) of gestation but was without effect on postpartum day 1.
      Furthermore, CGRP mRNA or peptide levels in dorsal root ganglia were not
      different between the L-NAME and control rats at any of the time points studied.
      These data indicate that in experimental preeclampsia, CGRP is playing a
      compensatory vasodilator role to attenuate the elevated blood pressure. The
      mechanism of this effect appears to be an enhanced vascular responsiveness to
      CGRP that is attenuated after the birth of pups.

PMID- 9039111
TI  - Selective guanylyl cyclase inhibitor reverses nitric oxide-induced
      vasorelaxation.
AB  - Effects of a novel soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ), were characterized on guanylyl cyclase activity in
      cytosolic fraction of COS-7 cells overexpressing the alpha 1 and beta 1 subunits
      of the rat soluble enzyme. ODQ was a noncompetitive inhibitor of soluble guanylyl
      cyclase with respect to Mn2+ or Mn(2+)-GTP and was a mixed
      competitive/noncompetitive inhibitor with respect to nitric oxide (NO) donation.
      ODQ (10 mumol/L) reduced deta nonoate-stimulated cGMP production in COS-7 cells
      overexpressing soluble guanylyl cyclase and in rat aortic vascular smooth muscle
      cells. ODQ did not inhibit particulate forms of the enzyme rat guanylyl cyclase
      A, -B, or -C, did not block NO synthase, and did not auto-oxidize deta nonoate
      donated NO in the presence of cells at physiological pH. Therefore, ODQ is a
      selective inhibitor of soluble guanylyl cyclase. Using ODQ in isolated aortic
      ring preparations, we tested the hypothesis that soluble guanylyl cyclase
      mediates vasorelaxant activity associated with NO. Phenylephrine (100 nmol/L)
      precontracted, isolated rat aortas were relaxed in a concentration-dependent
      manner by deta nonoate (0.01 to 100 mumol/L) and nitroglycerin (0.01 to 300
      mumol/L). ODQ (10 mumol/L) attenuated deta nonoate- and nitroglycerin-mediated
      relaxation of contracted aortas. ODQ had no effect on natriuretic peptide-, 8
      bromo-cGMP-, isoproterenol-, or bimakalim-mediated aortic relaxation. These
      results support the hypothesis that soluble guanylyl cyclase mediates
      vasorelaxant activity associated with nitric oxide.

PMID- 9039112
TI  - Regulation of potassium channels in coronary arterial smooth muscle by
      endothelium-derived vasodilators.
AB  - Recent studies have suggested that coronary endothelial cells produce and release
      nitric oxide (NO), prostaglandin I2, and epoxyeicosatrienoic acids (EETs). These
      endothelium-derived vasodilators play an important role in the control of
      coronary vascular tone. However, the mechanism by which these endothelium-derived
      vasodilators cause relaxation of coronary arterial smooth muscle has yet to be
      determined. This study characterized and compared the effects of NO,
      prostaglandin I2, and 11,12-EET on the two main types of potassium channels in
      small bovine coronary arterial smooth muscle: the large conductance Ca(2+)
      activated K+ channels (KCa) and 4-aminopyridine-sensitive delayed rectifier K+
      channels (Kdrf). In cell-attached patches, nonoate, an NO donor, activated both
      KCa and Kdrf channels. The open probability of both KCa and Kdrf channels
      increased 10- to 25-fold when nonoate was added to the bath at concentrations of
      10(-6) to 10(-4) mol/L. 11,12-EET (10(-8) to 10(-4) mol/L) also increased the
      activity of the KCa channels in a concentration-dependent manner, but it had no
      effect on the activity of the Kdrf channels, even in the highest concentration
      studied (10(-4) mol/L). In contrast to the effect of 11,12-EET, iloprost, a
      prostaglandin I2 analogue (10(-6) to 10(-4) mol/L), produced a concentration
      dependent increase in the activity of Kdrf channels without affecting the KCa
      channels. In conclusion, all three endothelium-derived vasodilators act to open
      potassium channels; however, the channel types that they affect are different. NO
      activates both KCa and Kdrf channels; 11,12-EET activates only the KCa channels;
      and prostaglandin I2 activates only the Kdrf channels.

PMID- 9039113
TI  - Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.
AB  - Acute exogenous estrogen administration enhances endothelial function in
      postmenopausal women. To evaluate the effect of endogenous estrogen on
      endothelium-dependent vasodilation, in 10 fertile normotensive women (age range
      45 to 51 years) we studied the changes in forearm blood flow (strain-gauge
      plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5,
      1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium
      nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent
      vasodilator, in basal conditions and within 1 month after ovariectomy. As control
      subjects, 10 matched healthy women were also evaluated. In basal condition,
      vasodilation to acetylcholine and sodium nitroprusside was similar in patients
      and control subjects. Ovariectomy was followed by endogenous estrogen deprivation
      (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P <
      .01) reduction in acetylcholine-induced vasodilation compared with baseline
      (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%;
      ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected
      by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/
      36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was
      repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50
      micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine
      induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/-
      43.1%; P < .01 versus ovariectomy), which was no longer different from baseline,
      whereas the response to sodium nitroprusside was not affected (maximum percent
      increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a
      protective role of endogenous estrogen on endothelium-dependent vasodilation in
      the forearm vascular bed of normotensive women.

PMID- 9039114
TI  - Cyclooxygenase inhibition restores nitric oxide activity in essential
      hypertension.
AB  - To evaluate whether cyclooxygenase constrictor substances can impair nitric oxide
      mediated vasodilation in essential hypertension, in seven normotensive subjects
      (43.3 +/- 4.1 years; BP, 117 +/- 6/81 +/- 2 mm Hg) and seven essential
      hypertensive patients (47.1 +/- 5.2 years; BP, 151 +/- 8/98 +/- 4 mm Hg) we
      studied forearm blood flow (strain-gauge plethysmography) modifications induced
      by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 15 micrograms.100 mL-1.min
      1) in basal conditions, during infusion of NG-monomethyl-L-arginine (L-NMMA; 100
      micrograms.100 mL-1.min-1), a nitirc oxide synthase inhibitor, or indomethacin
      (50 micrograms.100 mL-1.min-1), a cyclooxygenase inhibitor, or simultaneous
      indomethacin and L-NMMA. In normotensives, vasodilation to acetylcholine was
      blunted by L-NMMA (maximum flow increase: 671 +/- 64% and 386 +/- 42%,
      respectively; P < .01), and this effect was unchanged by indomethacin. In
      contrast, in hypertensive patients, vasodilation to acetylcholine (maximum flow
      increase: 458 +/- 33%) was unchanged by L-NMMA. Indomethacin significantly (P <
      .01) increased the response to acetylcholine (maximum flow increase: 635 +/- 53%)
      and restored the inhibitory effect of L-NMMA (maximum flow increase: 445 +/- 36%;
      P < .01 versus indomethacin alone). In an adjunctive seven normotensives (51.4 +/
      4.2 years; BP, 114 +/- 5/79 +/- 3 mm Hg) and seven essential hypertensives (53.2
      +/- 7.6 years; BP, 153 +/- 9/100 +/- 3 mm Hg) we repeated the same protocol by
      replacing L-NMMA with L-arginine (200 micrograms.100 mL-1.min-1), the substrate
      for NO synthase. In normotensives, vasodilation to acetylcholine was increased by
      L-arginine (maximum flow increase: 539 +/- 48% and 806 +/- 61%, respectively) and
      this effect was unchanged by indomethacin. In hypertensive patients, vasodilation
      to acetylcholine (maximum flow increase: 339 +/- 32%) was unchanged by L-arginine
      but was significantly (P < .01) increased by indomethacin (maximum flow increase:
      592 +/- 38%). Moreover, indomethacin restored the facilitatory effect of L
      arginine (maximum flow increase: 804 +/- 56%; P < .01 versus indomethacin alone).
      Therefore, cyclooxygenase inhibition restores nitric oxide-mediated vasodilation
      in essential hypertension, suggesting that cyclooxygenase-dependent substances
      can impair nitric oxide production.

PMID- 9039115
TI  - Relationship between insulin resistance and endothelium-dependent vascular
      relaxation in patients with essential hypertension.
AB  - The infusion of L-arginine induces the production of nitric oxide and stimulates
      the immediate secretion of insulin. To examine the relationship between insulin
      resistance and endothelium-dependent vascular relaxation in patients with
      essential hypertension, we evaluated the renal and insulin responses to L
      arginine, 500 mg/kg infused intravenously over 30 minutes, in 23 patients with
      mild essential hypertension who were neither obese nor diabetic and in 20
      normotensive control subjects. We found no difference between the two groups in
      blood glucose or insulin in the fasting condition. The renovascular relaxation
      induced by L-arginine was significantly less in patients with essential
      hypertension than in normotensive control subjects. The increase in plasma cyclic
      GMP in response to L-arginine was lower in hypertensive patients than in
      normotensive subjects. Although the serum concentrations of glucose in response
      to L-arginine were similar in the two groups, the serum insulin response of the
      essential hypertensives was significantly higher than that of the normotensive
      subjects. In all subjects, the peak cyclic GMP response to L-arginine was
      significantly correlated with the peak delta glucose/ delta insulin ratio
      response to L-arginine (r = .69, P < .001). Findings suggested that an impairment
      of endothelium-dependent renal vascular relaxation and a reduced sensitivity to
      insulin are present in patients with essential hypertension. A link may be
      present between the abnormality of the L-arginine/nitric oxide/cyclic GMP pathway
      and insulin resistance in patients with essential hypertension.

PMID- 9039116
TI  - Converting enzyme inhibitor improves forearm reactive hyperemia in essential
      hypertension.
AB  - Endothelial function is known to be impaired in essential hypertensive patients.
      In this study, we examined whether antihypertensive drugs improve forearm
      vasodilatory response to reactive hyperemia in 26 patients with essential
      hypertension (62 +/- 2 years) without diabetes mellitus, hyperlipidemia, coronary
      heart disease, or cerebrovascular disease. Antihypertensive drugs were never
      given or were discontinued for at least 4 weeks before the study. Patients were
      treated with monotherapy of either temocapril (2 or 4 mg, n = 15) or amlodipine
      (2.5 or 5 mg, n = 11) for 6 months. Forearm blood flow was measured by strain
      gauge plethysmography. Vasodilator response to the release of upper arm
      compression at 300 mm Hg for 5 minutes and to sublingual administration of
      nitroglycerin (0.3 mg) were assessed. Changes of forearm blood flow response to
      reactive hyperemia were significantly less in hypertensive patients (99 +/- 18%)
      than in age-matched normotensive control subjects (150 +/- 22%, P < .01, n = 39).
      Blood pressure (mm Hg) was similarly decreased by the treatment with temocapril
      (160 +/- 4/94 +/- 2 to 139 +/- 3/83 +/- 3, P < .001) or amlodipine (165 +/- 5/94
      +/- 3 to 141 +/- 4/82 +/- 3, P < .001). Response to nitroglycerin was not changed
      by either drug. Forearm vasodilatory response to reactive hyperemia was improved
      by temocapril (102 +/- 20% to 168 +/- 25%, P < .01) but not by amlodipine (97 +/-
      16% to 114 +/- 14%, NS). These results indicate that the treatment with the
      angiotensin-converting enzyme inhibitor temocapril improved forearm vasodilatory
      response to reactive hyperemia, suggesting its beneficial effect on endothelial
      function.

PMID- 9039117
TI  - Endothelial adhesion molecules and leukocyte integrins in preeclamptic patients.
AB  - Endothelial cell activation is important in the pathogenesis of preeclampsia;
      however, the nature of the activation is unknown. We investigated 22 patients
      with preeclampsia. 29 normotensive pregnancies, and 18 nonpregnant women to test
      the hypothesis that serum from preeclamptic patients induces expression of
      intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM
      1) and stimulates intracellular free calcium concentrations [Ca2+]i in cultured
      endothelial cells. We then asked whether the corresponding integrin adhesive
      counter receptors lymphocyte function-associated antigen-1 (CD11a/CD18),
      macrophage-1 antigen (CD11b/CD18), p150,95 (CD11c/CD18), and very late activation
      antigen-4 (CD49/CD29) are increased in patients with preeclampsia. In the
      pregnant women, the measurements were conducted both before and after delivery.
      Integrin expression was measured by fluorescent antibody cell sorting analysis
      using monoclonal antibodies. ICAM-1 and VCAM-1 were analyzed on endothelial cells
      by enzyme-linked immunosorbent assay. [Ca2+]i was measured with fura 2. Serum
      from preeclamptic patients increased endothelial cell ICAM-1 expression but not
      VCAM-1 expression. Preeclamptic patients' serum also increased [Ca2+]i in
      endothelial cells compared with serum from normal nonpregnant or normal pregnant
      women. Endothelial cell [Ca2+]i concentrations were correlated with the ICAM-1
      expression in preeclamptic patients (r = .80, P < .001) before but not after
      delivery. Expression of the integrin counter receptors on leukocytes was
      similarly increased in preclampsia and normal pregnancy compared with the
      nonpregnant state. The expression decreased significantly after delivery in both
      groups. Our results demonstrate that serum from preeclamptic women induces
      increased ICAM-1 surface expression on endothelial cells, while the expression of
      the integrin counterreceptors was not different. The effect on endothelial cells
      may be related to an increase in [Ca2+]i. The effect on cultured endothelial
      cells and the rapid decrease after delivery suggests the presence of a
      circulating serum factor which increases endothelial cell [Ca2+]i and enhances
      adhesion molecule expression.

PMID- 9039118
TI  - Cyclooxygenase-2 mediates increased renal renin content induced by low-sodium
      diet.
AB  - We hypothesized that neuronal nitric oxide synthase and cyclooxygenase-2, which
      both exist in the renal cortex, predominantly in the macula densa, play a role in
      the control of renal renin tissue content. We studied the possible role of
      neuronal nitric oxide synthase in regulating renal renin content by using mice in
      which the neuronal nitric oxide synthase gene has been disrupted (nNOS-/-)
      compared with its two progenitor strains, the 129/SvEv and the C57BL/6, to
      determine if the absence of neuronal nitric oxide synthase would result in
      decreased renal renin content or blunt the increase observed during low sodium
      intake. Renal renin content from cortical slices was determined in adult mice
      from all three strains maintained on a normal sodium diet. Renal renin content
      was significantly reduced in the nNOS-/- mice compared with the 129/SvEv and the
      C57BL/6 mice (3.11 +/- 0.23 versus 5.66 +/- 0.50 and 7.55 +/- 1.17 micrograms
      angiotensin l/mg dry weight, respectively; P < .005), suggesting that neuronal
      nitric oxide synthase may stimulate renal renin content under basal conditions.
      Neither selective pharmacological inhibition of neuronal nitric oxide synthase
      using 7-nitroindazole or disruption of the neuronal nitric oxide synthase gene
      affected the increase in renal content observed during dietary sodium
      restriction. The influence of cyclooxygenase-2 on renal renin content through a
      macula densa-mediated pathway was studied using a selective cyclooxygenase-2
      inhibitor, NS398, in 129/SvEv mice. A low-sodium diet increased renal renin
      content from 6.97 +/- 0.52 to 11.59 +/- 0.79 micrograms angiotensin l/mg dry
      weight (P < .005); but this increase was blocked by NS398. In addition, treatment
      with NS398 reduced renin mRNA in response to a low-sodium diet. Thus, increased
      renal renin content in response to dietary sodium restriction appears to require
      the induction of cyclooxygenase-2, while neuronal nitric oxide synthase appears
      to affect basal but not stimulated renal renin content.

PMID- 9039119
TI  - Vascular smooth muscle thromboxane A2 receptors mediate arachidonic acid-induced
      sudden death in rabbits.
AB  - We recently identified a subgroup of rabbits (called nonresponders) that were
      deficient in vascular thromboxane A2 receptors. Thromboxane A2-mediated platelet
      aggregation was not different between responders and nonresponders. In the
      present study, we utilized these nonresponders as a model to study the relative
      contribution of the platelet and vascular thromboxane A2 receptors to the
      observed hemodynamic responses associated with arachidonic acid-induced sudden
      death. Mean arterial pressure was slightly but not significantly lower in the
      nonresponders compared with the responders. However, nonresponders were protected
      from arachidonic acid-induced sudden death. While 100% of the responders died at
      the 2.0 mg dose of arachidonic acid, only 27% of nonresponders died at this same
      dose. Administration of the thromboxane A2 mimetic U46619 (5 micrograms/kg IV)
      decreased blood pressure by 41 +/- 6 mm Hg in responders but had no effect in the
      nonresponders. The affinity and density of thromboxane A2 receptors in cultured
      aortic vascular smooth muscle cells obtained from both responders and
      nonresponders were assessed using radioligand binding. The Kd values were not
      different (4.4 +/- 1.0 versus 2.4 +/- 0.6 nmol/L, responder versus nonresponder).
      However, there was a significant decrease in the density of receptors from
      vascular smooth muscle cells of nonresponders (Bmax = 397 +/- 59 versus 157 +/-
      59 fmol/10(6) cells, responder versus nonresponder, P < .01). U46619 produced a
      concentration-dependent increase in [3H]-thymidine incorporation into responder
      vascular smooth muscle cells but had no effect in the nonresponder cells. Using
      an anti-thromboxane A2 receptor antibody, we compared the amount of receptor
      expressed in aortic tissue obtained from responders and nonresponders. Consistent
      with the results observed with [3H]-thymidine uptake and radioligand binding
      assays, the expression of thromboxane A2 receptor protein was decreased in
      nonresponder compared with responder vascular tissue. Platelet thromboxane A2
      receptor expression was not different. These studies demonstrate that the
      vascular smooth muscle cells of nonresponder rabbits are deficient in the
      thromboxane A2 receptor. Furthermore, the reduction in arachidonic acid-induced
      sudden death in nonresponders indicates that the vascular smooth muscle
      thromboxane A2 receptor mediates this effect.

PMID- 9039120
TI  - Thromboxane is required for full expression of angiotensin hypertension in rats.
AB  - Recent studies suggest that thromboxane (TX) mediates a significant component of
      angiotensin II (ANG II)-induced hypertension. However, there is little
      information to support the hypothesis that this relationship is important during
      chronic, physiological increases in ANG II, particularly while controlling for
      variation in endogenous ANG II levels induced by TX inhibition. This study tested
      that hypothesis in 27 chronically instrumented rats. After baseline measurements,
      suppression of endogenous TX was induced and maintained throughout the study in
      13 rats by i.v. infusion of the TX synthesis inhibitor (TSI) U63557A: the other
      14 rats received vehicle. Baseline mean arterial pressure (MAP) was not different
      between groups and was unchanged by TSI or vehicle. Continuous inhibition of ANG
      II production was then initiated in both groups of rats by i.v. infusion of the
      angiotensin-converting enzyme inhibitor (ACEI) benazepril. ACEI reduced blood
      pressure similarly in vehicle and TSI rats, from 105 +/- 2 to 91 +/- 2 mm Hg and
      103 +/- 1 to 89 +/- 1 mm Hg, respectively. ANG II was then infused at 5 ng.kg
      1.min-1 i.v. for 7 days in six rats from each group to restore ANG II activity to
      baseline levels. This dose increased MAP to 103 +/- 2 and 101 +/- 1 mm Hg in
      vehicle and TSI rats, respectively, values not different from pre-ACEI levels.
      Seven TSI rats and eight vehicle rats received a higher dose of ANG II (20 ng.kg
      1.min-1 i.v.). After 7 days, MAP was higher in vehicle than in TSI rats (143 +/-
      5 versus 120 +/- 4 mm Hg). These results suggest that endogenous TX is an
      important determinant of MAP in ANG II hypertension but may have a diminished
      role in blood pressure regulation when ANG II is at normal and subnormal levels.

PMID- 9039121
TI  - Inhibition of renal outer medullary 20-HETE production produces hypertension in
      Lewis rats.
AB  - Recent studies have indicated that a deficiency in the production of 20
      hydroxyeicosatetraenoic acid (20-HETE) in the outer medulla of the kidney may
      contribute to the abnormalities in the renal handling of sodium and the
      development of hypertension in Dahl salt-sensitive rats. To determine whether a
      reduction in 20-HETE production in the outer medulla is sufficient to induce
      hypertension, an inhibitor of the renal metabolism of arachidonic acid by P450
      enzymes, 17-octadecenoic acid (17-ODYA), was chronically infused directly into
      the outer medulla of the left kidney of uninephrectomized Lewis rats fed a high
      salt diet. Renal medullary interstitial infusion of 17-ODYA (400 pmol/min)
      reduced the formation of 20-HETE in the outer medulla of the infused kidney by
      70% compared with values seen in the right kidney collected when the rat was
      uninephrectomized, but it had no effect on the production of 20-HETE in the renal
      cortex. After 5 days, mean arterial pressure rose from 115 +/- 2 to 142 +/- 2 mm
      Hg (n = 6) in the rats infused with 17-ODYA, while mean arterial pressure was not
      significantly altered in the rats infused with vehicle alone (116 +/- 1 versus
      117 +/- 2 mm Hg, n = 6). These results suggest that inhibition of the renal
      metabolism of arachidonic acid by P450 enzymes in the outer medulla of the kidney
      is sufficient to induce the development of hypertension in Lewis rats fed a high
      salt diet and support the view that P450 metabolites of arachidonic acid play an
      important role in the regulation of renal function and the long-term control of
      arterial pressure.

PMID- 9039122
TI  - Inhibition of 20-HETE production contributes to the vascular responses to nitric
      oxide.
AB  - Nitric oxide (NO) inhibits a variety of heme-containing enzymes, including NO
      synthase and cytochrome P4501A1 and 2B1. The present study examined whether NO
      inhibits the production of 20-hydroxyeicosatetraenoic acid (20-HETE) by
      cytochrome P4504A enzymes and whether blockade of the production of this
      substance contributes to the vascular effects of NO. Sodium nitroprusside (SNP;
      10(-5), 10(-4), and 10(-3) mol/L) reduced the production of 20-HETE by renal
      microsomes incubated with arachidonic acid to 71 +/- 5%, 29 +/- 4%, and 4 +/- 2%
      of control, respectively (n = 5). Similar results were obtained with the use of 1
      propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazino) (n = 3). To determine
      whether inhibition of 20-HETE contributes to the vasodilatory effects of NO, the
      effects of dibromo-dodecenyl-methylsulfimide (DDMS), a selective inhibitor of the
      formation of 20-HETE, on the response to SNP (10(-7) to 10(-3) mol/L) were
      examined in rat renal arterioles preconstricted with phenylephrine (n = 5). SNP
      increased vascular diameter in a concentration-dependent manner to 82 +/- 4% of
      control. After DDMS (25 mumol/L), SNP (10(-3) mol/L) increased vascular diameter
      by only 17 +/- 3%. The effects of DDMS on the mean arterial pressure (MAP) and
      renal blood flow (RBF) responses to infusion of an NO donor and a synthase
      inhibitor were also examined in thiobutabarbital-anesthetized, Sprague-Dawley
      rats. Infusion of MAHMA NONOate at 1, 3, 5, and 10 nmol/min reduced MAP by 16 +/-
      2, 30 +/- 3, 40 +/- 5, and 48 +/- 5 mm Hg and lowered renal vascular resistance
      (RVR) by 15 +/- 3%, 26 +/- 2%, 30 +/- 3%, and 34 +/- 4% of control. After DDMS
      (10 mg/kg, n = 7 rats), the MAP and RVR responses to 1-hexamine, 6-(2-hydroxy-1
      methyl-2-nitrohydrazino)N-methyl (MAHMA NONOate) averaged only 20% of those seen
      during control. In other experiments, MAP increased by 32 +/- 4% and RBF fell to
      56 +/- 5% of control after administration of N-nitro-L-arginine (L-NArg) (10
      mg/kg IV). After DDMS (10 mg/kg, n = 7 rats), MAP increased by only 19 +/- 4% and
      RBF fell by only 7 +/- 4% after L-NArg. These results indicate that NO inhibits
      cytochrome P4504A enzymes and that inhibition of the production of 20-HETE
      contributes to the vasodilatory effects of NO.

PMID- 9039123
TI  - Cholesterol enhances platelet-derived growth factor-BB-induced [Ca2+]i and DNA
      synthesis in rat aortic smooth muscle cells.
AB  - In the present study, we describe possible mechanisms by which
      hypercholesterolemia may contribute to the development of cardiovascular
      diseases. Treatment of rat aortic smooth muscle cells for 20 hours with
      cholesterol-rich liposomes (500 micrograms/mL cholesterol, 100 micrograms/mL low
      density lipoprotein) resulted in a 76 +/- 12% increase in total cholesterol
      content. The effects of cholesterol enrichment were examined by determination of
      changes in cell membrane fluidity. Fluidity of the cholesterol-enriched cell
      membranes was decreased at all temperatures between 15 degrees C and 40 degrees
      C. Changes in membrane fluidity in whole cell membranes represented changes in
      fluidity of microsomal membranes isolated by Percoll gradient
      ultracentrifugation. The basal [Ca2+]i and the maximal platelet-derived growth
      factor (PDGF)-BB-induced [Ca2+]i was elevated by 30% and 90% in cholesterol
      enriched cells, respectively. In contrast, the resting pH, and the PDGF-BB
      induced stimulation of the Na+/H+ exchange were not affected in cholesterol
      enriched cells. The effect of PDGF-BB on [3H]thymidine incorporation in
      cholesterol-enriched cells was elevated by 40% in comparison with untreated
      cells. Our findings show that cellular cholesterol may be involved in the
      development of vascular diseases via modulation of the PDGF-induced increase in
      [Ca2+]i and DNA synthesis in vascular smooth muscle cells.

PMID- 9039124
TI  - Mitogen-activated protein kinase activation is involved in platelet-derived
      growth factor-directed migration by vascular smooth muscle cells.
AB  - Migration of vascular smooth muscle cells (VSMCs) is a crucial response to
      vascular injury resulting in neointima formation and atherosclerosis. Platelet
      derived growth factor (PDGF-BB) functions as a potent chemoattractant for VSMCs
      and enhances these pathologies in the vasculature. However, little is known about
      the intracellular pathways that mediate VSMC migration. In the present study, we
      investigated the role of mitogen-activated protein kinase (MAPK) activation in
      this function, since PDGF-BB as well as other growth factors activate this
      pathway. Using an in-gel kinase assay, we observed that PD 98059 an inhibitor of
      MEK that activates MAP kinase, inhibited PDGF-BB-induced activation of ERK-1 and
      ERK-2 in cultured rat aortic smooth muscle cells in a concentration-dependent
      manner. In contrast, PDGF-mediated activation of intracellular calcium release
      was not affected by PD 98059. The chemotactic response of both rat aortic smooth
      muscle cells (RASMCs) and human umbilical vein smooth muscle cells (HUSMCs)
      toward PDGF-BB (10 ng/mL) was significantly reduced by PD 98059 (10 mumol/L) to
      41.7 +/- 7.1% in RASMCs (P < .01) and to 47.2 +/- 5.3% in HUSMCs (P < .01).
      Similar inhibition was seen at 30 mumol/L, less at 1 mumol/L. To further confirm
      the specificity of these results implicating the MAPK pathway, an antisense
      oligodeoxynucleotide (ODN) directed against the initiation translation site of
      rat ERK-1 and ERK-2 mRNA was used to suppress MAP kinase synthesis and function
      in rat VSMCs. Liposomal transfection with 0.4 mumol/L antisense ODN reduced ERK-1
      and ERK-2 protein by 65% (P < .01) after 48 hours. The chemotactic response to
      PDGF-BB (10 ng/mL) was reduced by 75% (P < .01) in rat VSMCs transfected with the
      same antisense ODN concentration. Sense and scrambled control ODNs (0.4 mumol/L)
      did not affect ERK-1 and ERK-2 protein concentrations or chemotaxis of VSMCs
      induced by PDGF-BB. These experiments provide the first evidence that activation
      of MAPK is a critical event in PDGF-mediated signal transduction regulating VSMC
      migration.

PMID- 9039125
TI  - Smooth muscle apoptosis during vascular regression in spontaneously hypertensive
      rats.
AB  - We previously reported that apoptosis is increased in smooth muscle cells
      cultured from the aorta of spontaneously hypertensive rats versus normotensive
      controls. As an initial in vivo exploration, we now examined smooth muscle cell
      apoptosis regulation during the regression of vascular hypertrophy in the
      thoracic aorta media of spontaneously hypertensive rats receiving the
      antihypertensive drug enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1),
      nifedipine (35 mg.kg-1.d-1), hydralazine (40 mg.kg-1.d-1), propranolol (50 mg.kg
      1.d-1), or hydrochlorothiazide (75 mg.kg-1.d-1) for 1 to 4 weeks starting at 10
      to 11 weeks of age. Three criteria were used to evaluate smooth muscle cell
      apoptosis: (1) oligonucleosomal fragmentation of the extracted aortic DNA, (2)
      reduction in aortic DNA content, and (3) depletion of smooth muscle cells in the
      arterial media. Arterial DNA synthesis was evaluated by [3H]thymidine
      incorporation in vivo. After 4 weeks of treatment, systolic blood pressure was
      reduced significantly by > 42% with losartan, enalapril, and hydralazine, and by
      23% with nifedipine, versus control values of 220 +/- 5 mm Hg. However these
      agents affected vascular growth and apoptosis differently. Losartan, enalapril,
      and nifedipine stimulated smooth muscle cell apoptosis threefold to fivefold
      before there was a significant reduction in DNA synthesis (> 25%), vascular mass
      (> 19%), or vascular DNA content (> 38%), and these treatments markedly reduced
      (by 38% to 50%) medial cell number as measured at 4 weeks by the three
      dimensional disector method. Losartan and nifedipine stimulated smooth muscle
      cell apoptosis before reducing blood pressure. In contrast, hydralazine did not
      affect vascular mass, apoptosis, or DNA synthesis, although blood pressure was
      lowered. Propranolol or hydrochlorothiazide failed to affect hypertension or
      vascular growth. Thus, smooth muscle cell apoptosis represents a novel
      therapeutic target for the control of hypertensive vessel remodeling in response
      to therapeutic agents.

PMID- 9039126
TI  - Dopamine D1-like receptor stimulation inhibits hypertrophy induced by platelet
      derived growth factor in cultured rat renal vascular smooth muscle cells.
AB  - Vascular smooth muscle cell (VSMC) hypertrophy is believed to play some roles in
      atherosclerosis. To elucidate the role of vascular D1-like receptors in VSMC
      hypertrophy, the effects of dopamine and specific D1-like receptor agonists SKF
      38393 and YM 435 on platelet-derived growth factor (PDGF) BB-mediated VSMC
      hypertrophy was studied. We observed that cells stimulated by PDGF-BB 5 ng/mL
      showed increased VSMC hypertrophy. These effects were prevented by coincubation
      with dopamine, SKF 38393, and YM 435 1-10 mumol/L, and this prevention was
      reversed by Sch 23390 1 to 10 mumol/L, a specific D1-like receptor antagonist.
      These actions are mimicked by forskolin 1 to 10 mumol/L, a direct activator of
      adenylate cyclase and 8-bromo-cAMP 0.1 to 1 mmol/L, and are blocked by a specific
      protein kinase A (PKA) inhibitor N-[2-(P-bromcoinnamylamino)ethyl]-5-isoquinoline
      sulfonamide (H89) but not blocked by its negative control. PDGF-BB (5 ng/mL)
      mediated mitogen-activated protein kinase (MAPK) activity was significantly
      suppressed by coincubation with D1-like receptor agonists, which were reversed by
      PKA inhibitor H 89. These results suggest that vascular D1-like receptor agonists
      inhibit hypertrophy of VSMC, possibly through PKA activation and suppression of
      activated MAPK activity.

PMID- 9039127
TI  - Alpha-thrombin stimulates sis-inducing factor-A DNA binding activity in rat
      aortic smooth muscle cells.
AB  - Exposure of rat aortic vascular smooth muscle cells to alpha-thrombin resulted in
      the appearance of sis-inducing factor-A (SIF-A)-like DNA binding activity. This
      response to alpha-thrombin was delayed (detectable at 1 hour) compared with the
      rapid activation (15 to 30 minutes) by platelet-derived growth factor and the
      cytokine interleukin-6. alpha-Thrombin-induced SIF-A was sensitive to treatment
      with the tyrosine kinase inhibitor genistein. The thrombin inhibitor hirudin
      prevented the alpha-thrombin-mediated SIF-A induction. Cycloheximide had no
      effect on the ability of alpha-thrombin to induce SIF-A, suggesting that
      induction does not require new protein synthesis. alpha-Thrombin-induced SIF-A
      could be resolved into two additional subcomplexes termed SIF-A, and SIF-As.
      Antibodies against Stat3 reacted with alpha-thrombin-induced SIF-Af, suggesting
      that Stat3 or a related protein is present in this subcomplex. Induction of SIF-A
      DNA binding activity may contribute to alpha-thrombin-mediated cellular
      responses, including wound healing, cell proliferation, and inflammation in the
      vasculature.

PMID- 9039128
TI  - Intima-media thickness of the carotid artery in hypertensive subjects and
      hypertrophic cardiomyopathy patients.
AB  - While hypertension is known to cause left ventricular and vascular hypertrophy,
      the relationship between alterations of vascular and cardiac structures in
      patients with hypertrophic cardiomyopathy has not been fully clarified. We
      measured intima-media thickness of carotid arteries by ultrasonography in
      patients with hypertrophic cardiomyopathy (n = 16), normotensive subjects (n =
      358), and hypertensive subjects (n = 386) in a cohort of 7940 male employees of a
      bus company. Our object was to determine whether vascular alteration occurs in
      hypertrophic cardiomyopathy similarly as in hypertension. Hypertrophic
      cardiomyopathy (wall thickness > or = 15 mm; asymmetrical hypertrophy without
      hypertension) was screened with family history and electrocardiography followed
      by echocardiography. The intima-media thickness in patients with hypertrophic
      cardiomyopathy (mean, 0.61 mm) did not differ from that of normotensive subjects
      (0.60 mm) but was significantly less than that of hypertensive subjects with left
      ventricular hypertrophy (wall thickness > or = 14 mm; n = 22; 0.73 mm). In a
      scatterplot of intima-media thickness versus interventricular septal thickness,
      these two parameters were significantly correlated in normotensives and
      hypertensives. The patients with hypertrophic cardiomyopathy distributed outside
      the 95% confidence range of the normotensive and hypertensive subjects. In
      summary, the increase in intima-media thickness of the carotid artery paralleled
      left ventricular hypertrophy in normotensive and hypertensive subjects. Patients
      with hypertrophic cardiomyopathy had a normal intima-media thickness regardless
      of the hypertrophied left ventricle. Thus, information on intima-media thickness
      may be useful in differentiating hypertensive left ventricular hypertrophy from
      hypertrophic cardiomyopathy.

PMID- 9039129
TI  - Angiotensin II signaling in vascular smooth muscle. New concepts.
AB  - Angiotensin II is a multifunctional hormone that affects both contraction and
      growth of vascular smooth muscle cells through a complex series of intracellular
      signaling events initiated by the interaction of angiotensin II with the AT1
      receptor. The cellular response to angiotensin II is multiphasic, involving
      stimulation within seconds of phospholipase C and Ca2+ mobilization; activation
      within minutes of phospholipase D, A2, protein kinase C, and MAP kinase; and
      stimulation after a period of hours of gene transcription and NADH/NADPH oxidase
      activity. Angiotensin II also activates numerous intracellular tyrosine kinases.
      In this respect, it shares some aspects of signaling with growth factor and
      cytokine receptors, including activation of phospholipase C-gamma, src, and ras;
      association of shc with grb2; and stimulation of the Jak/STAT pathway. The
      cellular events responsible for this unique series of events may involve receptor
      movement and the creation of a signaling domain. Elucidation of these pathways is
      important to our understanding of AT1 receptor function as a final effector of
      the renin-angiotensin system.

PMID- 9039130
TI  - Prolonged reduction of high blood pressure with an in vivo, nonpathogenic, adeno
      associated viral vector delivery of AT1-R mRNA antisense.
AB  - To produce a prolonged decrease in blood pressure, we have developed a
      nonpathogenic adeno-associated viral vector (AAV) with the antisense DNA for AT1
      R. AAV has many advantages over other viral vectors. AAV does not stimulate
      inflammation or immune reaction. AAV enters nondividing cells and does not
      replicate. Therefore, it is an appropriate choice for gene therapy. Recombinant
      AAV was prepared with a cassette containing a cytomegalovirus promoter and the
      cDNA for the AT1 receptor inserted in the antisense direction. The cassette was
      packaged in the virion. Stable transfection of NG108-15 cells with the PAAV-AS
      (plasmid AAV) antisense to AT1-R produced a significant reduction in AT1
      receptors. A single injection of the rAAV-AS (viral vector) was made in adult
      spontaneously hypertensive rats, either directly in the hypothalamus (1 microL)
      or in the lateral ventricles (5 microL). The result shows that there is a
      significant decrease of blood pressure (approximately 23 +/- 2 mm Hg) for up to 9
      weeks after injection. Control injections of mock vector produced no change in
      blood pressure during the same time period in age-matched controls. In young
      spontaneously hypertensive rats (3 weeks), a single intracardiac injection of
      recombinant rAAV-AS reduced blood pressure and slowed the development of
      hypertension compared with controls (P < .01). The results suggest that a
      prolonged reduction in high blood pressure can be achieved with AAV vectors
      delivering antisense to inhibit AT1 receptors with a single administration.

PMID- 9039131
TI  - Opposite regulation of Gax homeobox expression by angiotensin II and C-type
      natriuretic peptide.
AB  - Growth arrest-specific homeobox (Gax) gene was isolated from rat aorta cDNA
      library and its expression was largely confined to the cardiovascular tissues.
      Gax gene was rapidly downregulated by platelet-derived growth factor in vascular
      smooth muscle cells (VSMCs) and overexpressed Gax was reported to reduce the
      neointimal thickening after balloon injury in vivo. We have demonstrated that
      angiotensin II (Ang II) stimulates vascular growth. In contrast, we also reported
      that C-type natriuretic peptide (CNP) is secreted from vascular endothelial cells
      to act as a novel endothelium-derived relaxing peptide and inhibits vascular
      growth via cGMP cascade. In the present study, we examined the effects of Ang II
      and CNP on Gax gene expression in VSMCs. In quiescent rat aortic VSMCs. Gax mRNA
      (2 3 kb) level became negligible 6 hours after the addition of Ang II (10(-6)
      mol/L). The inhibitory action of Ang II on Gax mRNA expression (ED50: 10(-11)
      mol/L) was almost completely blocked by an AT1R antagonist, CV11974. In contrast,
      CNP 10(-6) mol/L augmented Gax mRNA expression to exhibit 1.8-fold increase of
      the control 12 hours after the stimulation. This effect of CNP was mimicked by
      the addition of 8-bromoadenosine 3'-5'-cyclic monophosphate. The addition of C
      ANF[4-23], an atrial natriuretic peptide-C receptor-specific agonist and devoid
      of stimulating cGMP production, exhibited no effect on Gax mRNA expression.
      Simultaneous administration of Ang II and CNP revealed that CNP (10(-6) mol/L)
      significantly attenuated the inhibitory action of Ang II (10(-10) mol/L) on Gax
      mRNA expression. These results suggest that Gax is a common transcription factor
      involved in the signaling pathway of vascular growth for Ang II and CNP and
      regulates the cell cycle and/or phenotype of VSMCs for vascular remodeling in
      hypertension and atherosclerosis.

PMID- 9039132
TI  - Bovine aortic endothelial cells contain an angiotensin-(1-7) receptor.
AB  - Angiotensin-(1-7) is a novel peptide of the renin-angiotensin system that
      counteracts the pressor and proliferative responses to angiotensin II. We now
      report that cultured bovine aortic endothelial cells contain a saturable, high
      affinity [125I]angiotensin-(1-7) binding site with an affinity of 19.3 +/- 10.7
      nmol/L and a density of 1351 +/- 710 fmol/mg protein. Angiotensin-(1-7) competed
      at a second lower-affinity site, with an IC50 of 2.9 mumol/L. The high-affinity
      angiotensin II receptor antagonist sarcosine1-isoleucine8-angiotensin II blocked
      [125I]angiotensin-(1-7) binding to bovine aortic endothelial cells at both a high
      (IC50 = 1.3 nmol/L) and a low-affinity (IC50 = 6.2 mumol/L) binding site. In
      contrast, D-alanine7-angiotensin-(1-7) completely blocked [125I]angiotensin-(1-7)
      binding, with an IC50 of 19.8 nmol/L, suggesting that D-alanine7-angiotensin-(1
      7) may selectively block responses to angiotensin-(1-7) in endothelial cells.
      Neither the AT1 antagonist losartan nor the AT2 antagonist PD 123319 exhibited
      significant competition for [125I]angiotensin-(1-7) binding to endothelial cells
      isolated from bovine aorta, in agreement with the absence of detectable mRNAs
      encoding typical angiotensin receptor subtypes 1 or 2 (AT1 or AT2). Angiotensin
      II also competed for [125I]angiotensin-(1-7) binding to bovine aortic endothelial
      cells; however, the relative affinity was 13-fold lower than angiotensin-(1-7),
      suggesting a preference for angiotensin-(1-7) over angiotensin II. These results
      demonstrate that bovine aortic endothelial cells contain a unique non-AT1, non
      AT2 angiotensin receptor that preferentially binds angiotensin-(1-7).

PMID- 9039133
TI  - Angiotensin-(1-7) augments bradykinin-induced vasodilation by competing with ACE
      and releasing nitric oxide.
AB  - Recent studies have shown that angiotensin-(1-7) [Ang-(1-7)] interacts with
      kinins and augments bradykinin (BK)-induced vasodilator responses by an unknown
      mechanism. In this study, we evaluated whether the potentiation of the BK-induced
      vasodilation by Ang-(1-7) may be attributable to inhibition of BK metabolism,
      release of nitric oxide, or both. Isometric tension was measured in intact canine
      coronary artery rings suspended in organ chambers. 125I-[Tyr0]-BK metabolism was
      determined in vascular rings by assessing the degradation of the peptide by high
      performance liquid chromatography. Ang-(1-7) augmented the vasodilation induced
      by BK in a concentration-dependent manner in rings preconstricted with the
      thromboxane analog U46619. The EC50 of BK (2.45 +/- 0.51 nmol/L versus 0.37 +/-
      0.08 nmol/L) was shifted leftward by 6.6-fold in the presence of 2 mumol/L
      concentration of Ang-(1-7). The response was specific for BK. since Ang-(1-7) did
      not augment the vasodilation induced by either acetylcholine (0.05 mumol/L) or
      sodium nitroprusside (0.1 mumol/L). Moreover, neither angiotensin I nor
      angiotensin II (Ang II) duplicated the augmented BK response of Ang-(1-7).
      Pretreatment of vascular rings with the nitric oxide synthase inhibitor, N omega
      nitro-L-arginine (L-NA; 100 mumol/L) completely abolished the effects of Ang-(1
      7) on BK-induced vasodilation whereas pretreatment with indomethacin (10 mumol/L)
      was without effect. The potent specific BK B2 receptor antagonist, Hoe 140.
      nearly abolished the BK and the Ang-(1-7) potentiated responses at 2 mumol/L,
      whereas at a lower concentration (20 nmol/L) Hoe 140 shifted the response curve
      to the right for both Ang-(1-7) and vehicle; however, the augmented response to
      Ang-(1-7) persisted. Preincubation of vascular rings with 20 mumol/L of the AT1
      (CV11974), AT2 (PD123319), or nonselective (Sar1 Thr8-Ang II) receptor
      antagonists had no significant effect on the Ang-(1-7)-enhanced vasodilator
      response to BK. Lisinopril (2 mumol/L) significantly enhanced the BK-induced
      vasodilator response while at the same time it abolished the synergistic action
      of Ang-(1-7) on BK. In addition, pretreatment with 2 mumol/L Ang-(1-7)
      significantly inhibited the degradation of 125I-[Tyr0]-BK and the appearance of
      the BK-(1-7) and BK-(1-5) metabolites in coronary vascular rings. Ang-(1-7)
      inhibited purified canine angiotensin converting enzyme activity with an IC50 of
      0.65 mumol/L. In conclusion. Ang-(1-7) acts as a local synergistic modulator of
      kinin-induced vasodilation by inhibiting angiotensin converting enzyme and
      releasing nitric oxide.

PMID- 9039134
TI  - Angiotensin II stimulates secretion of endogenous ouabain from bovine
      adrenocortical cells via angiotensin type 2 receptors.
AB  - Angiotensin II stimulates secretion of corticosteroids and ouabain-like activity
      from adrenocortical cells. Distinct adrenocortical angiotensin II receptor
      subtypes (AT1, AT2) have been described, and the present studies investigated
      their roles in steroid secretion. Using primary bovine adrenocortical cell
      cultures under serum free conditions, angiotensin II stimulated the secretions of
      aldosterone, cortisol, and endogenous ouabain as verified by high-performance
      chromatography. The dose-response curves for stimulated steroid secretion were
      parallel with unitary slopes while the half-maximally effective concentrations of
      angiotensin II were 0.31 to 0.38 nmol/L for secretions of aldosterone and
      cortisol and 2.3 nmol/L for endogenous ouabain. The nonselective mammalian
      antagonist (Sar1-Ile8) angiotensin II blocked stimulated secretion of all three
      steroids without affecting basal output. In the presence of the AT1 antagonist
      DuP753, angiotensin II-stimulated secretions of aldosterone and cortisol were
      blocked while secretion of endogenous ouabain was unaffected. In the presence of
      the AT2 antagonist PD123319, both basal and angiotensin II-stimulated secretions
      of aldosterone and cortisol were normal while stimulated secretion of endogenous
      ouabain was inhibited. The secretion of endogenous ouabain was activated
      maximally by the AT2 agonist CGP42112 under conditions in which aldosterone
      secretion was unaffected. These results demonstrate that AT2 receptors stimulate
      secretion of endogenous ouabain from bovine adrenocortical cells. The specificity
      of AT1 and AT2 receptor stimulation indicates that separate signaling mechanisms
      having minimal cross talk control the adrenocortical secretions of
      corticosteroids and cardiac-active steroids. Adrenocortical AT2 receptors may be
      important in the adaptation to low salt diets and other conditions in which
      angiotensin II is increased.

PMID- 9039135
TI  - Regulation of growth of the adrenal gland in DOC-salt hypertension. Role of
      angiotensin II receptor subtypes.
AB  - To investigate the role of the renin-angiotensin system in the regulation of
      adrenal growth in deoxycorticosterone (DOC)-salt hypertensive rats, and the
      adrenal gene expression of angiotensin AT1 and AT2 receptors, three groups of
      uninephrectomized rats + DOC pellet + 0.9% NaCl were given water (DOC), losartan
      (DOC-L), or ramipril (DOC-R) by gavage. Controls had sham surgery and water
      gavage. Tail-cuff systolic and mean intra-arterial blood pressures were
      significantly higher in the three DOC groups than in controls and not different
      among the groups. Adrenal weight of DOC was slightly but not significantly
      greater than that of controls, while those of DOC-L and DOC-R were greater than
      that of controls (P < .01). Northern blots showed that AT1 and AT2 gene
      expression was significantly reduced in DOC (by 33% and 60%), while that of AT1
      (but not AT2) was significantly reduced further (versus control and DOC) in DOC-L
      and DOC-R. There were negative correlations between adrenal weight and AT1 (r = 
      .80, P < .0001) or AT2 (r = -.60, P < .005). We conclude that DOC-salt
      hypertension downregulates adrenal AT1 and AT2 gene expression by different
      mechanisms. Removal of the effects of angiotensin by losartan or ramipril
      downregulates AT1 further and promotes adrenal growth, indicating the presence of
      an AT1-mediated growth-inhibitory action of angiotensin II on the adrenal gland.
      These observations constitute an additional example of a growth-inhibitory role
      for the AT1 receptor, opposite to its more common growth-promoting actions in
      other organs and tissues.

PMID- 9039136
TI  - Expression of guanylyl cyclase-A/atrial natriuretic peptide receptor blocks the
      activation of protein kinase C in vascular smooth muscle cells. Role of cGMP and
      cGMP-dependent protein kinase.
AB  - To understand the molecular mechanisms of cellular signaling of atrial
      natriuretic peptide (ANP), we have studied its effect on the enzymatic activity
      of endogenous and overexpressed protein kinase C (PKC) in rat thoracic aortic
      vascular smooth muscle (RTASM) cells. Angiotensin II (ANG II), endothelin-1 (ET
      1), and 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated fourfold to
      fivefold PKC activity in PKC-alpha cDNA-transfected RTASM cells. However,
      pretreatment of these cells with ANP significantly inhibited the agonist
      stimulated PKC activity in a dose-dependent manner. The inhibitory effect of ANP
      was more effective if cells were transfected with both PKC-alpha and guanylyl
      cyclase-A/atrial natriuretic peptide receptor (Npra) cDNAs. The agonist
      stimulated PKC activity was also inhibited if RTASM cells were pretreated with
      cGMP analog 8-bromo-cGMP; however, the treatment of cells with a cAMP analog,
      dibutyryl-cAMP, did not show any discernible effect. The pretreatment of cells
      with Npra antagonist A-71915, significantly blocked the production of cGMP as
      well as the inhibitory effect of ANP on PKC activity. To further examine whether
      the antagonistic action of ANP and 8-bromo-cGMP on agonist-stimulated PKC
      activity were mediated through cGMP-dependent protein kinase (PKG), cells were
      treated with ANP or 8-bromo-cGMP and activators of PKC in the presence of KT
      5823, a specific inhibitor of PKG. The treatment of cells with KT-5823
      significantly attenuated the inhibitory effects of both ANP and 8-bromo-cGMP on
      agonist-stimulated PKC activity. The results from these studies provide strong
      evidence that ANP antagonizes the activation of PKC in RTASM cells, involving
      guanylyl cyclase-A receptor Npra and second messenger cGMP. Our data further
      support the notion that ANP acts as a negative mediator of signaling cross-talks
      between Npra and PKC in a cGMP-dependent manner, probably involving cGMP
      dependent protein kinase in this process.

PMID- 9039137
TI  - G-protein function is reduced in hypertension.
AB  - A functional impairment in vasodilator tone may be important in the pathogenesis
      and/or maintenance of elevated peripheral vascular resistance in hypertension.
      Previous studies of hypertensive subjects have demonstrated impaired beta
      adrenergic-mediated vasodilation paralleling a reduction in lymphocyte beta
      adrenergic-stimulated adenylyl cyclase activity. We have suggested that this
      impairment is related to a defect in G-protein function. To determine whether
      this defect alters the coupling between the G-protein complex and adenylyl
      cyclase, we performed [3H]forskolin binding studies in lymphocytes from
      hypertensive subjects, older normotensive subjects, and younger normotensive
      control subjects. Maximal specific [3H]forskolin binding was used as an index of
      adenylyl cyclase binding sites. Gpp(NH)p-, NaF/AlCl3-, and isoproterenol
      stimulated binding were used as indices of G-protein/adenylyl cyclase coupling.
      In the absence of other stimulators, maximal [3H]forskolin binding was not
      significantly different among groups. However, both Gpp(NH)p- and isoproterenol
      stimulated [3H]forskolin binding were significantly decreased in lymphocytes from
      hypertensive subjects. Overall, Gpp(NH)p- and isoproterenol-stimulated
      [3H]forskolin binding were significantly inversely correlated with blood
      pressure. No differences in NaF/AlCl3-stimulated [3H]forskolin binding were
      detected between groups. These studies indicate that G-protein/adenylyl cyclase
      coupling is impaired in lymphocytes from younger hypertensive subjects and may
      contribute to the blood pressure-related defect in beta-adrenoceptor-stimulated
      adenylyl cyclase activity.

PMID- 9039138
TI  - High human renin hypertension in transgenic rats.
AB  - We developed a model of spontaneously high human renin hypertension in the rat by
      producing two transgenic strains, one for human angiotensinogen with the
      endogenous promoter and one for human renin with the endogenous promoter. Neither
      transgenic strain was hypertensive. These strains were then crossed, producing a
      double transgenic strain. The double transgenic rats, both males and females,
      developed severe hypertension (mean systolic pressure, 200 mm Hg) and died after
      a mean of 55 days if untreated. The rats had a human plasma renin concentration
      of 269 +/- 381 (+/-SD) ng angiotensin I (Ang I)/mL per hour, plasma renin
      activity of 177 +/- 176 ng Ang I/mL per hour, rat angiotensinogen concentration
      of 1.49 +/- 1 microgram Ang I/mL, and human angiotensinogen concentration of 78
      +/- 39 micrograms Ang I/mL (n = 49). Control rats had plasma renin activity of
      3.7 +/- 3.9 ng Ang I/mL per hour and rat angiotensinogen of 1.32 +/- 0.16
      micrograms Ang I/mL. Angiotensinogen transgene expression by RNase protection
      assay was ubiquitously present but most prominent in liver. Renin transgene
      expression was high in kidney but absent in liver. The rats featured severe
      cardiac hypertrophy, with increased cross section of cardiomyocytes but little
      myocardial fibrosis. The kidneys showed atrophic tubules, thickened vessel walls,
      and increased interstitium. Both the angiotensin-converting enzyme inhibitor
      lisinopril and the specific human renin inhibitor remikiren lowered blood
      pressure to normal values. Double transgenic mice have been developed that
      exhibit features quite similar to those described here; their gene expressions
      are similar. The specificity of rodent and human renin is similarly documented.
      Although many elegant physiological studies can now be done in mice, rats
      nevertheless offer flexibility, particularly in terms of detailed cardiac and
      renal physiology and pharmacology. We conclude that this double transgenic strain
      will facilitate simultaneous investigation of genetic and pathophysiological
      aspects of renin-induced hypertension. The fact that human renin can be studied
      in the rat is a unique feature of this model.

PMID- 9039139
TI  - Effects of chronic ETA-receptor blockade in angiotensin II-induced hypertension.
AB  - Angiotensin II, a constrictor and mitogen of vascular smooth muscle cells,
      affects the release of endothelium-derived factors such as nitric oxide or
      endothelin-1. This study investigated the influence of endothelin-1, using the
      selective endothelin A receptor antagonist LU135252, on blood pressure and
      endothelial function in angiotensin II-induced hypertension in the rat. Two weeks
      of angiotensin II administration (200 ng/kg per minute) increased systolic blood
      pressure (+35 +/- 5 mm Hg; tail-cuff method) compared with placebo (P < .05).
      LU135252 alone did not affect systolic pressure but lowered the angiotensin II
      induced pressure increase (P < .05). In isolated aortic rings, endothelium
      dependent relaxations to acetylcholine were reduced in the angiotensin II group
      (P < .05 versus placebo) and improved by concomitant chronic LU135252 treatment
      (P < .05 versus angiotensin II). Blood pressure elevation strongly correlated
      with impaired endothelium-dependent relaxations to acetylcholine (r = -.967).
      LU135252 did not affect endothelium-independent relaxations to sodium
      nitroprusside, which were diminished after angiotensin II treatment (P < .05). In
      quiescent rings, chronic angiotensin II administration enhanced endothelium
      dependent contractions to acetylcholine, which were reduced by LU135252 (P <
      .05). Impaired contractions to endothelin-1 and norepinephrine in the angiotensin
      II group were normalized after treatment with LU135252 (P < .05). Thus, chronic
      therapy with LU135252 partially prevents angiotensin II-induced hypertension and
      the alternations of the endothelial function observed in this experimental model.

PMID- 9039140
TI  - Role of renal nerves in afferent arteriolar reactivity in angiotensin-induced
      hypertension.
AB  - The objective of this study was to determine the contribution of renal nerves to
      the enhanced afferent arteriolar reactivity observed in angiotensin II (Ang II)
      induced hypertension. Uninephrectomized Sprague-Dawley rats were divided into
      four groups: sham rats, renal-denervated rats, Ang II-infused (at 40 ng/min for
      13 days) rats, and Ang II-infused+renal-denervated rats. With the use of an
      implanted arterial catheter, mean arterial pressure (MAP) was monitored in
      conscious rats. Ang II infusion resulted in a progressive increase in MAP from 98
      +/- 1 (day 0) to 166 +/- 7 mm Hg (day 13). This increase in MAP was attenuated in
      denervated rats and averaged 136 +/- 3 mm Hg on day 13. Kidneys were harvested on
      day 13 for microcirculatory experiments or measurement of intrarenal Ang II
      levels. Basal afferent arteriolar diameter was similar in all groups, and group
      averages ranged from 19.6 to 20.7 microns. Chronic Ang II infusion increased
      intrarenal Ang II levels. Renal denervation did not alter this effect. Increasing
      perfusion pressure from 100 to 160 mm Hg reduced afferent arteriolar diameter
      significantly by 11.2 +/- 0.6% in the sham group and by a similar degree in the
      remaining three groups. Superfusion with Ang II (10 nmol/L) reduced afferent
      arteriolar diameter by 34.3 +/- 2.0% in the sham group. This response was
      enhanced in Ang II-infused (62.3 +/- 3.4%) but not in renal-denervated or Ang II
      infused+renal-denervated rats. Additionally, the enhanced afferent arteriolar
      reactivity to Ang II was not influenced by adrenergic receptor blockade. The
      afferent arteriolar response to norepinephrine was enhanced in renal-denervated,
      Ang II-infused, and Ang II-infused+renal-denervated rats compared with sham
      controls. Administration of the calcium ionophore A23187 decreased afferent
      arteriolar diameter similarly in all four groups. These results indicate that
      renal nerves contribute to the development of hypertension and to the enhanced
      afferent arteriolar responsiveness to Ang II elicited by chronic Ang II infusion.

PMID- 9039141
TI  - Sodium intake, angiotensin II receptor blockade, and baroreflex function in
      conscious rats.
AB  - The hypothesis that endogenous angiotensin II (Ang II) chronically supports
      baroreflex control of lumbar sympathetic nerve activity (LSNA) and heart rate
      (HR) via AT1 but not AT2 receptors was tested in conscious, normotensive rats.
      Rats were fed either a sodium deficient diet (LS) to increase circulating Ang II
      or a high-sodium diet (HS) for 2 to 3 weeks. One to two days after surgery to
      implant catheters and nerve electrodes, baroreflex curves were produced before
      and 40 minutes after intravenous administration of the AT1 antagonist losartan
      (10 mg/kg) or the AT2 antagonist PD123319 (500 micrograms/kg + 50 micrograms.kg
      1.min-1). Mean arterial pressure (MAP) after losartan was maintained at basal
      levels with methoxamine. Forty minutes after losartan in LS rats, LSNA (46 +/- 5
      to 22 +/- 1% max) and HR (414 +/- 7 to 387 +/- 8 bpm) were decreased (P < .05).
      Losartan decreased reflex control of LSNA more in LS than in HS rats (P < .05),
      as indicated by reductions in maximum LSNA (98 +/- 2 to 78 +/- 3% max) and
      minimum LSNA (42 +/- 5 to 21 +/- 5% max). Losartan also shifted reflex control of
      LSNA to a lower pressure in both groups, but the effect was larger in LS rats (
      21 +/- 3 [LS] versus -9 +/- 2 [HS] mm Hg at basal LSNA; P < .05). Maximum gain
      was unaltered in either group. Similarly, losartan reduced maximum HR (534 +/- 6
      to 495 +/- 9 bpm) and shifted the HR curve leftward (114 +/- 5 to 105 +/- 4 mm
      Hg) in LS but not in HS rats. In general, no changes were observed in MAP or
      baroreflex control of LSNA and HR after PD123319 in LS rats. These results
      suggest that in conscious, normotensive LS rats, endogenous Ang II supports LSNA
      and HR over a wide MAP range via AT1 but not AT2 receptors.

PMID- 9039142
TI  - Improvement in baroreflex function by an oral angiotensin receptor antagonist in
      rats with myocardial infarction.
AB  - Impaired baroreflex function is a factor responsible for poor prognosis in
      myocardial infarction patients. Using logistic function curves, we calculated the
      maximal gain of the baroreflex control of renal sympathetic nerve activity (RSNA)
      and heart rate in conscious Wistar-Kyoto and spontaneously hypertensive rats
      whose left anterior descending artery had been ligated 4 weeks earlier. We
      further investigated whether 3-week oral treatment with the angiotensin II type 1
      receptor antagonist TCV-116 would improve the baroreflex in rats with myocardial
      infarction. The maximal gain of the mean arterial pressure-RSNA relation in
      spontaneously hypertensive rats with myocardial infarction and treated with
      vehicle (1.7 +/- 0.1% control per mm Hg) was smaller than the gain in sham
      operated hypertensive rats (2.3 +/- 0.1% control per mm Hg). After 3-week oral
      treatment with TCV-116, the maximal gain of the arterial pressure-RSNA relation
      in hypertensive rats with myocardial infarction was 2.3 +/- 0.1% control per mm
      Hg and significantly greater than the gain in infarcted and vehicle-treated
      hypertensive rats. In hypertensive rats, the maximal gain of the arterial
      pressure-heart rate relation of infarcted and TCV-116-treated rats was larger
      than in infarcted and vehicle-treated rats but significantly smaller than in sham
      operated rats. These results demonstrate that oral treatment with an angiotensin
      receptor antagonist is effective in restoring the impaired baroreflex caused by
      myocardial infarction and that endogenous angiotensin II is one of the critical
      factors involved in the impaired baroreflex in myocardial infarction.

PMID- 9039143
TI  - Cardiopulmonary baroreflex in NaCl-induced hypertension in borderline
      hypertensive rats.
AB  - Borderline hypertensive rats fed an 8% NaCl diet develop increased arterial
      pressure in association with increased cardiopulmonary baroreflex sensitivity
      compared with rats fed a 1% NaCl diet. We performed experiments to localize the
      site of sensitization within the cardiopulmonary baroreflex. To determine whether
      decreased cardiopulmonary baroreflex sensitivity, as seen in other models of NaCl
      induced hypertension, develops later in the course of the disease, we studied an
      older backcross population derived from borderline hypertensive rats and Wistar
      Kyoto rats. Anesthetized borderline hypertensive rats fed 1% and 8% NaCl diets
      were volume-loaded while right atrial pressure, afferent vagal nerve activity,
      and renal sympathetic nerve activity were recorded. In 28- to 30-week-old
      backcross rats fed an 8% NaCl diet, renal sympathetic nerve activity,
      natriuresis, and diuresis were measured before and during volume loading. Renal
      sympathetic nerve activity was analyzed with the sympathetic peak detection
      algorithm. Increases in afferent vagal nerve activity and renal
      sympathoinhibition were similar in borderline hypertensive rats on either diet
      during a right atrial pressure rise of 3 mm Hg. In backcross rats, correlations
      between arterial pressure and renal sympathoinhibition, natriuresis, or diuresis
      were not found. During volume loading, the peak height of synchronized renal
      sympathetic nerve discharges decreased while their frequency increased.
      Attenuated renal sympathoinhibition during acute increases in intravascular
      volume is not involved in the development or maintenance of NaCl-induced
      hypertension in borderline hypertensive rats. Renal sympathetic nerve activity
      decreases because of a reduction in the number of active renal sympathetic nerve
      fibers.

PMID- 9039144
TI  - Kallikrein-kinin system and blood pressure sensitivity to salt.
AB  - We evaluated the blood pressure response to chronic salt loading in a rat strain
      inbred for low urinary kallikrein excretion. Low-kallikrein rats showed greater
      systolic blood pressure values (130 +/- 1 versus 114 +/- 2 mm Hg in controls; P <
      .05) at 9 weeks of age. Systolic blood pressure was increased after 10 days of
      dietary sodium loading in the low-kallikrein group and remained unchanged in
      controls (153 +/- 1 versus 112 +/- 2 mm Hg, P < .01). In additional experiments,
      blood pressure sensitivity to salt was tested in low-kallikrein rats receiving a
      chronic infusion of rat glandular kallikrein (1.7 micrograms/day per 100 g body
      weight, IV) or vehicle. Systolic blood pressure of vehicle-treated rats was
      increased by salt loading (from 138 +/- 1 to 158 +/- 2, 153 +/- 1, and 145 +/- 2
      mm Hg at 5, 10, and 15 days, respectively; P < .01), while it remained unchanged
      in the kallikrein-treated group (from 136 +/- 2 to 146 +/- 5, 140 +/- 2, and 134
      +/- 4 mm Hg at 5, 10, and 15 days, respectively; P = NS). Urinary kallikrein
      excretion was increased by kallikrein infusion (from 13.6 +/- 1.4 to 17.8 +/- 2.1
      nanokatals per 24 hours; P < .01). Plasma immunoreactive kallikrein levels were
      higher in the kallikrein-treated group (66.4 +/- 4.4 versus 57.7 +/- 1.4 ng/mL in
      vehicle-treated rats; P < .05). On normal sodium diet, the ratio of kidney weight
      to body weight was lower in low-kallikrein rats (329 +/- 5 versus 370 +/- 8
      mg/100 g body weight in controls; P < .01). This difference was associated with a
      decreased number of glomeruli per unit square area and increased width of
      Bowman's space. These results indicate that kallikrein replacement prevents the
      exaggerated blood pressure increase observed in rats with a genetically
      determined defect in urinary kallikrein excretion. Histological abnormalities are
      present at different levels in the nephron, and they may be functionally related
      to the altered cardiovascular and renal phenotype of this strain.

PMID- 9039145
TI  - Blockade of bradykinin B2 receptors prevents the increase in capillary density
      induced by chronic angiotensin-converting enzyme inhibitor treatment in stroke
      prone spontaneously hypertensive rats.
AB  - We investigated the mechanism of action of the ACE inhibitor-induced increase in
      cardiac capillary length density. Stroke-prone spontaneously hypertensive rats
      were treated prenatally and up to the age of 20 weeks with the ACE inhibitor
      ramipril (0.01 and 1 mg/kg per day PO) and the AT1 receptor antagonist losartan
      (30 mg/kg per day PO). The contribution of endogenous bradykinin potentiation to
      the ACE inhibitor actions was assessed by cotreatment with the bradykinin B2
      receptor antagonist Icatibant (0.5 mg/kg per day, SC via osmotic minipumps) from
      6 to 20 weeks of age. At the end of the treatment period, cardiac capillary
      length density was measured stereologically using the orientator method. The
      development of hypertension and left ventricular hypertrophy was prevented by
      high- but not low-dose ramipril and was not affected by chronic bradykinin B2
      receptor blockade. Low- and high-dose ramipril significantly increased cardiac
      capillary length density (3577 +/- 279, n = 11 and 3988 +/- 300 mm/mm3; n = 10; P
      < .05) compared with vehicle-treated animals (2935 +/- 137 mm/mm3; n = 13). These
      effects were abolished by chronic bradykinin B2-receptor blockade. The bradykinin
      antagonist alone was without effect on cardiac capillary length density. Losartan
      prevented hypertension and left ventricular hypertrophy but did not significantly
      alter cardiac capillary length density (3429 +/- 309 mm/mm3; n = 7). Our results
      demonstrate that chronic ACE inhibitor treatment can increase cardiac capillary
      length density in stroke-prone spontaneously hypertensive rats independently of a
      reduction in blood pressure or left ventricular hypertrophy. This effect is
      related to the ACE inhibitor-induced potentiation of endogenous bradykinin since
      it was prevented by chronic bradykinin B2-receptor blockade and was not observed
      following antihypertensive treatment with the AT1-receptor antagonist losartan.

PMID- 9039146
TI  - Effect of high salt intake in mutant mice lacking bradykinin-B2 receptors.
AB  - Renal kinins release prostaglandins and nitric oxide via the B2 receptor,
      promoting diuresis and natriuresis; hence, they may also contribute significantly
      to blood pressure regulation. We hypothesized that mutant mice lacking the gene
      encoding for the bradykinin-B2 receptor (B2-KO) become hypertensive when placed
      on a long-term high-salt diet. To test this, B2-KO and control mice were placed
      on either a normal (0.2%) or high-Na+ diet (3.15% in food plus 1% saline as
      drinking water) for 8 weeks. Systolic blood pressure was determined during weeks
      6 and 8 by a computerized tail-cuff system. At the end of the 8-week period, mice
      were anesthetized for determination of mean blood pressure, renal blood flow, and
      renal vascular resistance. In B2-KO mice maintained on high Na+, systolic blood
      pressure was 15 mm Hg higher than in knockout animals on normal Na+ (P < .01). In
      contrast, there was no difference in blood pressure in control mice fed either a
      normal or a high-Na+ diet. Consistent with the systolic blood pressure data,
      direct mean arterial pressure revealed that B2-KO mice on high Na+ were
      hypertensive (115 +/- 6 in B2-KO on high-Na+ diet versus 79 +/- 2.8 in B2-KO on
      normal Na+, P < .0001); renal blood flow was reduced by 20% (P < .05) and renal
      vascular resistance was doubled (P < .0001) compared with B2-KO mice on normal
      Na+. In contrast, control mice on high Na+ were normotensive and tended to have
      increased renal blood flow and decreased renal vascular resistance compared with
      control mice on a normal Na+ diet. These findings indicate that kinins play an
      important role in preventing salt-sensitive hypertension; this may be achieved by
      maintaining renal blood flow under conditions of high salt intake.

PMID- 9039147
TI  - Hypotension in transgenic mice overexpressing human bradykinin B2 receptor.
AB  - Bradykinin binds to its receptor at target organs and exerts a wide spectrum of
      biological activities including vasodilation, smooth muscle contraction and
      relaxation, pain, and inflammation. To gain a better insight into the
      physiological function of this potent vasoactive peptide, we created transgenic
      mice that harbor the human bradykinin B2 receptor transgene under the control of
      the Rous sarcoma virus 3'-LTR promoter (RSV-cHBKR). Expression of HBKR in these
      transgenic mice was identified in the aorta, brain, heart, lung, liver, kidney,
      uterus, and prostate gland by reverse transcription-polymerase chain reaction
      Southern blot analysis. Two transgenic mouse lines expressing the human B2
      receptor resulted in a significant reduction of blood pressure (84.2 +/- 0.6 mm
      Hg, n = 28; 76.9 +/- 0.8 mm Hg, n = 24; P < .001) compared with the control
      littermates (96.9 +/- 0.4 mm Hg, n = 52). Administration of Hoe 140, a bradykinin
      B2 receptor antagonist, restored the blood pressure of the transgenic mice to
      normal levels within 1 hour, and the effect diminished within 4 hours. The
      transgenic mice displayed enhanced blood pressure-lowering effect induced by a
      bolus intra-aortic injection of kinin and showed increased response in kinin
      induced uterine smooth muscle contractility compared with control littermates.
      These studies show that overexpression of human bradykinin B2 receptor causes a
      sustained reduction of blood pressure in transgenic mice. They also suggest that
      the B2 receptor-mediated signal transduction pathway plays a role in blood
      pressure regulation.

PMID- 9039148
TI  - Gonadal hormones modulate deoxycorticosterone-salt hypertension in male and
      female rats.
AB  - We have shown previously that, in rats with deoxycorticosterone (DOC)-salt
      hypertension, arterial blood pressure rises more rapidly and reaches a higher
      level in male than in female rats and that the course of the hypertension was
      ameliorated by gonadectomy in male rats and exacerbated by gonadectomy in female
      rats. The present investigation was undertaken to examine the role of the gonadal
      steroid hormones in modulating the course of DOC-salt hypertension in the rat.
      Our previous findings with respect to the effects of gender and gonadectomy on
      DOC-salt hypertension were confirmed in this study. Chronic treatment with
      gonadal steroids was begun 1 week before the start of the DOC-salt protocol. 17
      beta-Estradiol attenuated the course of the hypertension in intact male rats and
      in gonadectomized females. Testosterone exacerbated the development of the
      hypertension in gonadectomized male rats but was without effect in intact
      females. Progesterone alone had no effect on the hypertension in ovariectomized
      rats but when given to ovariectomized rats in combination with estradiol
      transiently prevented the ameliorating effect of the estradiol. These effects of
      the gonadal steroid hormones could not be attributed to effects of saline intake.
      Thus, these findings demonstrate that the gonadal steroid hormones play an
      important role in modulating the pathogenesis of DOC-salt hypertension in the
      rat. It is suggested that the effects of the gonadal hormones on the course of
      the hypertension may be due to modulation of the cardiovascular and renal actions
      of vasopressin, since vasopressin is required for this model of hypertension.

PMID- 9039149
TI  - Kidney 11 beta-HSD2 is inhibited by glycyrrhetinic acid-like factors in human
      urine.
AB  - We have previously shown that human urine contains substances that, like
      glycyrrhetinic acid, inhibit 11 beta-HSD1. We have named these substances
      "glycyrrhetinic acid-like factors" or GALFs. We now have found that human urine
      contains measurable quantities of both 11 beta(HSD1)- and 11 beta(HSD2)-GALF
      inhibitory substances. Both are markedly elevated in pregnancy. Their chemical
      and high-performance liquid chromatography (HPLC) characteristics suggest that
      several of the GALFs are steroidal. Large quantities of neutral 11 beta(HSD1)-
      and 11 beta(HSD2)-GALFs can be extracted directly from urine into ethyl acetate,
      yielding fraction EA1. Hydrolysis of the GALFs remaining in the aqueous phase by
      beta-glucuronidase markedly increases the total amounts of GALFs, with the
      majority now being ethyl acetate extractable (fraction EA2). These EA2 post
      hydrolysis GALFs can be separated by HPLC resulting in at least six components
      with inhibitory activity against each isoenzyme. Only two GALF peaks are active
      against both 11 beta-HSD1 and 11 beta-HSD2. The others are peaks with specific 11
      beta(HSD1)- and 11 beta(HSD2)-GALF inhibitory activity. The GALFs in the same
      posthydrolysis EA2 extract are also inhibitory toward the 11 beta-HSD1 that is
      present in vascular smooth muscle where they may play a role in the mechanisms
      controlling blood pressure. We have also found that 11 beta-HSD2 is selectively
      inhibited by 5 alpha- (but not by 5 beta-) reduced steroids. GC-MS analysis of
      the 11 beta(HSD2)-GALFs in EA2 is now being performed to determine whether this
      group includes 3 alpha,5 alpha-ring A-tetrahydro-reduced derivatives of steroids.

PMID- 9039150
TI  - Role of substance P in blood pressure regulation in salt-dependent experimental
      hypertension.
AB  - The participation of substance P in the pathogenesis of five models of
      experimental hypertension, ie, DOCA-salt, subtotal nephrectomy, one-kidney-one
      clip renovascular, two-kidney-one clip renovascular, and spontaneous
      hypertension, was evaluated via an acute infusion of a newly synthesized potent,
      specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP
      96,345. In conscious unrestrained rats, CP 96,345 induced significant and
      sustained increases in mean arterial pressure of DOCA-salt, subtotal nephrectomy,
      and one-kidney-one clip renovascular hypertensive rats but only small and
      nonsignificant changes in blood pressure of two-kidney-one clip renovascular and
      spontaneously hypertensive rats. CP 96,345 had no effect on the blood pressure of
      sham-treated controls and Wistar-Kyoto rats. This NK-1 receptor antagonist did
      not significantly affect the heart rate of any experimental model studied. The
      data suggest that endogenous substance P may act as a partial counterregulatory
      mechanism against vasoconstriction in models of salt-dependent hypertension.

PMID- 9039151
TI  - Hypothalamic substance P release. Attenuated angiotensin responses in mRen2(27)
      transgenic rats.
AB  - Increases in arterial pressure and paraventricular nucleus vasopressin release in
      response to intracerebroventricular injections of angiotensin peptides are
      blunted in mRen2(27) renin transgenic [TG(+)] rats. Intraventricular injections
      of tachykinin peptides mimic several of the actions of angiotensin peptides, and
      angiotensin peptides evoke substance P release from hypothalamic brain slices.
      The present study assessed whether diminished substance P release occurs in
      response to angiotensin peptides in TG(+) rats. Systolic blood pressure at 8 to
      12 weeks of age averaged 197 +/- 4 mm Hg (n = 20; P < .05) in TG(+) rats compared
      with 123 +/- 4 mm Hg in normotensive control [TG(-)] rats (n = 18). Body weight
      was lower in hypertensive than in normotensive rats (305 +/- 14 versus 344 +/- 13
      g, respectively; P < .05). Brain slices from hypothalamus were perfused at 37
      degrees C with oxygenated Krebs' bicarbonate buffer. Substance P was measured
      before (basal) and during perfusion with either Krebs' buffer (control) or 2
      mumol/L angiotensin-(1-7) or angiotensin II. Basal substance P release was 92 +/-
      10 pg/g wet tissue in TG(+) and 98 +/- 12 pg/g in TG(-) rats (P > .05).
      Angiotensin-(1-7) and angiotensin II significantly increased substance P release
      from hypothalamus of TG(-) rats (82% and 70% above control: P < .05) but not
      TG(+) rats. These studies further support the hypothesis that the cardiovascular
      effects of angiotensin peptides are mediated in part by substance P and that this
      relationship is blunted in a hypertensive model that results from excess tissue
      production of angiotensins.

PMID- 9039152
TI  - Pulsatile compression of the rostral ventrolateral medulla in hypertension.
AB  - The rostral ventrolateral medulla (RVLM) has been known to be a major regulating
      center of sympathetic and cardiovascular activities. An association between
      essential hypertension and neurovascular compression of the RVLM has been
      reported in clinical observations, including magnetic resonance imaging (MRI)
      studies. To reconfirm this relationship, we performed MRI using a high-resolution
      512 x 512 matrix in patients with essential and secondary hypertension and in
      normotensive subjects. The duration of hypertension and the degree of organ
      damage by hypertension were not significantly different between the two
      hypertension groups. Neurovascular compression of the RVLM was observed in 74% of
      the essential hypertension group, and the incidence of compression was
      significantly higher than in the secondary hypertension group (11%) or in the
      normotensive group (13%) (P < .01). These results from the clinical studies
      suggest that neurovascular compression of the RVLM is, at least in part, causally
      related to essential hypertension. Although blood pressure elevation by pulsatile
      compression of the RVLM in an experimental baboon model has already been
      reported, its underlying mechanism is not well known. Accordingly, we performed
      experiments to investigate whether pulsatile compression of the RVLM would
      increase arterial pressure and to elucidate the mechanism of the pressor response
      in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma
      levels of epinephrine and norepinephrine were increased by pulsatile compression
      of the RVLM. The pressor response was abolished by intravenous treatment with
      hexamethonium or RVLM injection of kainic acid. In summary, the results from the
      MRI studies suggest that neurovascular compression of the RVLM is, at least in
      part, causally related to essential hypertension. This was supported by the
      results from experimental studies using rats indicating that pulsatile
      compression of the RVLM increases arterial pressure by enhancing sympathetic
      outflow.

PMID- 9039153
TI  - Enalapril and losartan reduced cardiac mass and improved coronary hemodynamics in
      SHR.
AB  - Among the multiple mechanisms postulated for the increased risk of hypertensive
      left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a
      strong possibility. This study was designed to compare the effects of treatment
      with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist
      (losartan) on systemic and coronary hemodynamics and to determine whether the
      combination of these two renin-angiotensin system (RAS) inhibitor would be as or
      more effective in reducing mean arterial pressure (MAP), left ventricular (LV)
      mass, and improving coronary hemodynamics than either regimen alone. Thus, 23
      week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap
      water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their
      combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as
      normotensive controls. After 12 weeks, systemic and coronary hemodynamics were
      determined (15 microns radiolabeled microspheres) at baseline, during maximal
      treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and
      losartan equally reduced MAP and LV mass in association with a decreased total
      peripheral resistance. The RAS combination reduced MAP and LV mass more than
      either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit
      of LV mass did not differ among the groups. Although enalapril did not improve
      coronary flow reserve (CFR), it diminished minimal coronary vascular resistance
      (MCVR); losartan improved both. However, the combination was more effective than
      either agent alone, reaching values close to normotensive WKY controls. In
      conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and
      MCVR in untreated SHR, but losartan alone and in combination with enalapril
      improved systemic and coronary hemodynamics more than enalapril alone.

PMID- 9039154
TI  - Combined sympathetic suppression and angiotensin-converting enzyme inhibition in
      congestive heart failure.
AB  - Neurohormonal activation is a pathogenic contributor and prognostic marker in
      congestive heart failure (CHF). While angiotensin-converting enzyme (ACE)
      inhibition is now first-line therapy, sympathetic inhibition has only lately been
      proposed to this aim. Recently, we reported improvement of preload parameters by
      sympathetic suppression with clonidine. In the present paper we studied the
      effects of a single oral dose of clonidine 0.15 mg+captopril 6.25 mg combination,
      compared with captopril 6.15+placebo in a single-blind parallel study on 16
      patients with Class III or IV CHF (13 males, 3 females, aged 62 +/- 8 years, with
      an ejection fraction of 33 +/- 8%). Hemodynamic and hormonal measurements were
      taken at baseline after a diagnostic cardiac catheterization and again 2 hours
      after treatment. The results indicate that preload parameters such as RAP, PCWP
      and MPAP decreased significantly with the combination therapy but not with
      captopril alone. On the contrary, SVR decreased significantly with both
      treatments and SVI increased significantly with both-but the latter change was
      significantly greater with the captopril/clonidine combination than with
      captopril alone. Suppression of plasma norepinephrine occurred with the
      combination only (evidently attributable to clonidine), whereas plasma renin
      activity increased with both regimens, due apparently to captopril. Our results
      indicate that the combination of clonidine with captopril induces significant
      improvements in both preload and afterload parameters of CHF and correction of
      activated neurohormones, suggesting additive hemodynamic and hormonal benefits
      from the two treatment modalities.

PMID- 9039156
TI  - Hoechst Marion Roussel Hypertension Research Clinical Fellowship Award 1996.

PMID- 9039155
TI  - Oral calcium supplementation reduces intraplatelet free calcium concentration and
      insulin resistance in essential hypertensive patients.
AB  - We evaluated the effect of oral calcium supplementation on blood pressure,
      calcium metabolism, and insulin resistance in essential hypertension. After
      receiving a standard diet with 500 mg of calcium per day during a 4-week period,
      20 nondiabetic, essential hypertensive patients were randomized in a double-blind
      fashion to receive oral calcium supplementation (1500 mg of calcium per day) or
      placebo for 8 weeks. At the end of the 4-week period of low-calcium diet and
      after the 8-week period of intervention, we measured blood pressure (by both
      office and 24-hour ambulatory blood pressure monitoring), calcium-regulating
      hormones [urinary hydroxyproline and serum osteocalcin, parathormone, and
      1,25(OH)2-vitamin D3], intraplatelet free calcium concentration, fasting plasma
      glucose and insulin levels, and the insulin-sensitivity index (euglycemic
      hyperinsulinemic clamp). Compared with patients maintained at low calcium intake,
      essential hypertensive patients under oral calcium supplementation significantly
      reduced serum osteocalcin (from 22.2 +/- 1.9 to 17.9 +/- 2.0 micrograms/L; P =
      .0015), parathormone (from 4.20 +/- 0.38 to 3.30 +/- 0.36 pmol/L; P = .0003), and
      1,25(OH)2-vitamin D3 (from 98.0 +/- 11.0 to 61.6 +/- 5.7 pmol/L; P = .0062).
      Likewise, we found a significant reduction in intraplatelet free calcium
      concentration (from 35.9 +/- 1.2 to 26.5 +/- 0.8 nmol/L; P = .0005) and fasting
      plasma insulin levels (from 71.8 +/- 5.9 to 64.6 +/- 6.2 pmol/L; P = .05) and a
      significant increase in the insulin-sensitivity index (from 2.89 +/- 0.77 to 4.00
      +/- 0.95 mg.kg-1.min-1; P = .0007). None of these parameters were significantly
      modified in patients maintained at low calcium intake. Office and 24-hour mean
      values of systolic and diastolic blood pressure did not change after 8 weeks of
      oral calcium supplementation or placebo.

PMID- 9039157
TI  - Council for High Blood Pressure Research Lifetime Achievement Award.

PMID- 9039158
TI  - CIBA Award for hypertension research 1996.

PMID- 9039159
TI  - CIBA Award for hypertension research 1996.

PMID- 9039160
TI  - Harry Goldblatt Award 1996.

PMID- 9039161
TI  - Arthur C. Corcoran Memorial Lecturer 1996.

PMID- 9039162
TI  - Antiphospholipid antibodies and the antiphospholipid antibody syndrome.
AB  - The antiphospholipid antibody syndrome is a multiple-system disorder
      characterized by persistently elevated antiphospholipid antibodies and/or
      arterial or venous thrombosis, thrombocytopenia, or recurrent spontaneous
      abortion. Anticardiolipin antibodies and the lupus anticoagulant are different
      classes of antiphospholipid antibodies associated with this disorder. Cutaneous
      manifestations are common and may be the presenting sign of the underlying
      disease. This article reviews the clinical manifestations, laboratory assays,
      histopathologic features, and treatment of the antiphospholipid antibody
      syndrome.

PMID- 9039163
TI  - Itraconazole therapy is effective for pedal onychomycosis caused by some
      nondermatophyte molds and in mixed infection with dermatophytes and molds: a
      multicenter study with 36 patients.
AB  - BACKGROUND: Onychomycosis of the toenail caused by nondermatophyte molds alone or
      in combination with dermatophytes is difficult to eradicate with standard
      antifungal therapy. OBJECTIVE: Our purpose was to determine the effectiveness of
      itraconazole in the treatment of toenail onychomycosis caused by molds alone or
      in combination with dermatophytes. METHODS: We treated 36 patients with this drug
      given as continuous dosing (100 or 200 mg/ day) for 6 to 20 weeks or as a 1-week
      pulse dosing (200 mg twice daily for 1 week per month) for two to four pulses.
      RESULTS: Patients with toenail onychomycosis with the following organisms were
      treated: Aspergillus spp. (eight patients), Fusarium spp. (four patients),
      Scopulariopsis brevicaulis (23 patients), and Alternaria spp. (one patient).
      Nineteen patients had onychomycosis with a mixed origin. At follow-up, 12 months
      after therapy was initiated, clinical and mycologic cure was achieved in 15 of 17
      patients (88%) with onychomycosis caused by a single mold. In patients with mixed
      infection, a clinical cure was obtained in 16 of 19 patients (84%) and a
      mycologic cure in 13 of 19 patients (68%). CONCLUSION: Itraconazole appears to be
      effective and safe for the treatment of toenail onychomycosis caused by some
      nondermatophyte molds alone or in combination with dermatophytes.

PMID- 9039164
TI  - Hydroxyurea dermopathy: a unique lichenoid eruption complicating long-term
      therapy with hydroxyurea.
AB  - BACKGROUND: Hydroxyurea is usually a well tolerated antitumor agent. OBJECTIVE:
      Our purpose was to describe a distinct clinical and histologic eruption in
      patients receiving long-term hydroxyurea therapy. METHODS: The clinical,
      histologic, and immunopathologic features of six patients with hydroxyurea
      dermopathy are described. RESULTS: Three women and three men were identified. The
      average age was 61 years. Hydroxyurea had been used for an average of 5 years.
      Lichenoid papules, telangiectasia, and poikilodermatous lesions on the dorsal
      hands and digits were the most common findings. Interface dermatitis, focal
      lichenoid reaction with epidermal atrophy, and Civatte bodies were the most
      common histologic findings. Endothelial swelling also was noted. Cytoid staining
      with multiple conjugates was the most common immunopathologic finding. Four
      patients showed significant improvement after discontinuation of hydroxyurea.
      CONCLUSION: A distinct cutaneous reaction to long-term administration of
      hydroxyurea has been characterized. Cessation of treatment is necessary for
      healing or improvement. We have designated this eruption hydroxyurea dermopathy.

PMID- 9039165
TI  - PUVA-induced phototoxicity: incidence and causes.
AB  - BACKGROUND: Phototoxicity is the most significant short-term adverse effect of
      PUVA therapy. OBJECTIVE: We attempted to determine the incidence and possible
      causes of phototoxicity of sufficient degree to cause interruption of treatment.
      METHODS: A retrospective study was conducted of 16,506 PUVA treatments given to
      414 patients in two treatment centers. RESULTS: Phototoxicity occurred in 10.9%
      of patients and was an adverse effect in 0.3% of treatments. Problems with the
      treatment protocol were the main cause. CONCLUSION: Phototoxicity is a common
      adverse effect, and patients should be warned of this potential occurrence.
      Awareness of the causes may help to reduce the incidence of this problem.

PMID- 9039166
TI  - Neonatal lupus erythematosus: analysis of HLA class II alleles in mothers and
      siblings from seven Japanese families.
AB  - BACKGROUND: Neonatal lupus erythematosus (NLE) is a syndrome characterized by
      dermatitis and congenital heart block. The disease is mostly associated with
      transplacental passage of maternal anti-Ro(SS-A) or anti-La(SS-B) antibodies.
      Maternal HLA-DR3 and DQ2 alleles are associated with NLE in white and North
      American black populations. OBJECTIVE: We sought evidence of a potential genetic
      disposition to NLE in mothers with a relatively homogeneous ethnic background.
      METHODS: Class II human major histocompatibility complex HLA-DRB1, DQA1, DQB1,
      and DPB1 alleles were determined by polymerase chain reaction-restriction
      fragment length polymorphism in anti-Ro(SS-A)-positive mothers as well as in
      infants from seven Japanese families with siblings concordant or discordant for
      disease expression of NLE. RESULTS: All seven mothers had two or three DQ alleles
      of DQA1 and DQB1 possessing specific amino acid residues, which are reportedly
      associated with anti-Ro(SS-A) autoantibody response in white and black
      populations. There was no class II HLA profile that distinguished disease
      manifestations of NLE in infants. CONCLUSION: The HLA class II allele
      associations with anti-Ro(SS-A) autoantibodies that have been noted in other
      ethnic groups were also found in Japanese anti-Ro(SS-A)-positive mothers whose
      infants had NLE, suggesting shared susceptibility factors across racial barriers
      in maternal predisposition to Ro(SS-A) autoimmune response.

PMID- 9039167
TI  - T-cell cytokine network in cutaneous lupus erythematosus.
AB  - BACKGROUND: A variety of immunologic abnormalities have been described in
      systemic and experimental lupus erythematosus (LE). Several T-cell defects,
      especially in helper T (Th) cell cytokines, have been reported. OBJECTIVE: Our
      purpose was to identify the Th cytokine profile in cutaneous LE. METHOD: Total
      RNA was extracted from punch biopsy specimens from 19 patients with cutaneous LE
      (nine, discoid LE; two, subacute cutaneous LE; and eight, systemic LE) and from
      four healthy control subjects. RNA was reverse transcribed into complementary DNA
      and amplified with polymerase chain reaction (PCR) primers specific for
      interleukin-2 (IL-2), IL-4, IL-5, IL-10, interferon gamma (IFN-gamma), and beta
      actin. PCR products were detected by agarose gel electrophoresis and Southern
      blot with 32P-labeled, nested probes. RESULTS: Sixteen of 19 cutaneous LE
      specimens lacked IL-2, all were negative for IL-4, and 10 of 19 had detectable IL
      10, whereas IFN-gamma and IL-5 messenger RNAs were present in the majority of LE
      specimens. IFN-gamma and IL-10 mRNAs were found in all normal skin controls,
      whereas IL-2, IL-4, and IL-5 mRNAs were undetectable. Functional IFN-gamma
      protein was evidenced by intercellular adhesion molecule-1 and HLA-DR staining of
      keratinocytes in nine of nine LE specimens but not in normal skin. The pattern of
      cytokine mRNAs, intercellular adhesion molecule-1, and/or HLA-DR expression in
      cutaneous LE specimens did not vary with different subtypes of LE, antinuclear
      antibody titer, or the magnitude of inflammation. CONCLUSION: The presence of IL
      5 mRNA in cutaneous LE specimens suggests that Th type 2 cells combine with local
      IFN-gamma production to augment disease and may be related to the pathophysiology
      of cutaneous LE.

PMID- 9039168
TI  - Epiluminescence microscopy of small pigmented skin lesions: short-term formal
      training improves the diagnostic performance of dermatologists.
AB  - BACKGROUND: Epiluminescence microscopy (ELM) makes subsurface structures of the
      skin accessible for in vivo examination and provides additional criteria for the
      clinical diagnosis of pigmented skin lesions (PSLs). We demonstrated that ELM
      increases diagnostic sensitivity in dermatologists formally trained in the use of
      this technique but decreases diagnostic ability in dermatologists not formally
      trained in its application. OBJECTIVE: Our purpose was to determine the effects
      of short formal ELM training on the diagnostic performance of 11 previously
      untrained dermatologists. METHODS: One hundred image-pairs of randomly selected
      histologically proven PSLs, photographed with (ELM) and without oil immersion
      (surface microscopy), were presented by slide projection to the testees. To
      evaluate the effects on diagnostic performance before and after short-term
      training, we used the receiver-operator characteristics technique. RESULTS:
      Without training the use of ELM did not enhance diagnostic accuracy, but rather
      decreased it in 8 of 11 testees. In contrast, after 9 hours of formal training in
      ELM the diagnostic performance of the testees was significantly enhanced with an
      average gain of 8.4%. CONCLUSION: Our data confirm that formal training is
      required for the useful application of the ELM technique.

PMID- 9039169
TI  - Topical calcipotriol in childhood psoriasis.
AB  - BACKGROUND: The use of topical calcipotriol in adults with psoriasis is safe and
      effective. OBJECTIVE: Our purpose was to study the efficacy and safety of
      calcipotriol in children. METHODS: A multicenter, prospective, 8-week, double
      blind, parallel group study was conducted in 77 children. Response to treatment
      was assessed by means of the Psoriasis Area and Severity Index (PASI) in that the
      intensity of redness, thickness, and scaliness as well as the area involved are
      scored. The children were 2 to 14 years of age and had stable psoriasis,
      involving less than 30% of the body surface. Forty-three children were assigned
      to receive calcipotriol ointment and 34 to receive placebo. Nine children dropped
      out of the study, six in the calcipotriol-treated group and three in the placebo
      treated group. RESULTS: Both treatment groups (calcipotriol and placebo) showed
      significant improvement in PASI from baseline to the end of treatment, and the
      difference was not statistically significant. No serious side effects, in
      particular including those relating to calcium and bone metabolism, were
      recorded. CONCLUSION: Calcipotriol ointment was statistically significantly more
      effective than its vehicle in terms of the investigator's overall assessment and
      reduction in redness and scaliness but not in terms of PASI score.

PMID- 9039170
TI  - Circulating adhesion molecules as prognostic factors for cutaneous melanoma.
AB  - BACKGROUND: Overexpression of adhesion molecules in tissues of human neoplasms,
      including malignant melanoma, has been reported to be clinically relevant, but
      the predictive value of circulating adhesion molecules for clinical outcome and
      life expectancy in patients with primary malignant melanoma (PMM) and metastases
      of primary malignant melanoma (MMM) remains undetermined. OBJECTIVE: Our purpose
      was to examine the prognostic relevance of circulating adhesion molecules, namely
      circulating CD44 standard (cCD44std), and the isoforms CD44v5 (cv5), CD44v6
      (cv6), and CD44v10(cv10), circulating intercellular adhesion molecule-1 (cICAM
      1), and circulating platelet/endothelial cell adhesion molecule-1 (cPECAM-1,
      CD31). METHODS: Levels of cCD44std, cv5, cv6, cv10, cICAM-1, and PECAM-1 were
      measured by enzyme-linked immunosorbent assays in 119 patients with PMM and MMM,
      in 12 persons with dysplastic nevi (Clark's nevi), and in 28 patients with
      inflammatory cutaneous diseases. RESULTS: Patients with PMM, MMM, and
      inflammatory cutaneous diseases showed an elevation in levels of cCD44std and
      cICAM-1 compared with normal blood donors, but these levels were not
      significantly increased. Levels of cv5, cv6, and cv10 were not increased, and
      cPECAM-1 was only marginally elevated. Even in patients with clinically provable
      systemic or cutaneous metastases and in five patients who died of MMM, levels did
      not differ significantly compared with normal blood donors; this was also
      independent of the mode of therapy. CONCLUSION: Circulating CD44std and the
      isoforms cv5, cv6, and cv10, cICAM-1, and cPECAM-1 were detectable in persons
      with dysplastic nevi and in patients with PMM and MMM. None of the measured
      adhesion molecules was significantly elevated and of prognostic relevance in any
      of the subgroups studied. However, some of the patients with PMM and MMM showed
      high levels of cCD44std and cICAM-1; that finding should prompt us to examine
      these patients in more detail.

PMID- 9039171
TI  - Annular erythema associated with lupus erythematosus/Sjogren's syndrome.
AB  - BACKGROUND: Annular-polycyclic and papulosquamous lesions are associated with
      subacute cutaneous lupus erythematosus (SCLE). In some Asian cases, annular
      erythema has been associated with Sjogren's syndrome (SS). However, the relation
      between the two is unclear. OBJECTIVE: Our purpose was to clarify the clinical
      manifestations and immunologic features of patients with annular erythema.
      METHODS: This study included 15 patients with annular erythema. Systemic,
      serologic, and genetic findings were analyzed. RESULTS: Histologic examination
      showed perivascular and periappendageal lymphocytic infiltrates in all patients.
      However, LE-specific epidermal changes were observed in only three (20%).
      Although all patients at least partially demonstrated features of LE or SS, eight
      (53%) fulfilled the American Rheumatism Association criteria for systemic LE
      (SLE) and five (33%) were diagnosed with SS. Renal (20%) and central nervous
      system (7%) involvement was observed. Anti-Ro(SS-A) and anti-La(SS-B) antibodies
      were detected in nine (60%) and seven (47%) patients, respectively. There were no
      histocompatibility antigen (HLA) haplotype differences. CONCLUSION: Annular
      erythema in Asian patients is the counterpart of subacute skin lesions of LE in
      whites, except for the paucity of LE-specific histopathologic findings and HLA
      DR3 tissue type.

PMID- 9039172
TI  - Extensive pure venous malformations in the upper or lower limb: a review of 27
      cases.
AB  - BACKGROUND: Extensive pure venous malformations (VMs) involving the entire lower
      or upper limb and adjacent trunk form a particular group of rare vascular
      malformations. OBJECTIVE: Our purpose was to review 27 cases of extensive limb
      VMs and describe their characteristics and management. METHODS: Cases of
      extensive limb VMs were investigated, treated, and observed for a mean of 7
      years. RESULTS: Eleven cases involved the upper limbs and 16 involved the lower
      limbs. All involved skin and muscle. In 81% of cases in the lower limb there was
      also knee joint involvement that created severe functional impairment.
      Ultrasonography with Doppler (duplex scans), computed tomographic scans, and
      magnetic resonance imaging were helpful noninvasive diagnostic procedures in
      these patients, whereas arteriography and phlebography were less informative.
      Muscle involvement was present in 100% of patients and bone abnormalities in 63%.
      Leg length was either normal or there was slight limb undergrowth, except in
      three patients who had minor overgrowth of the affected limb. Coagulation
      profiles demonstrated localized intravascular coagulation in 88% of patients. The
      majority of patients had conservative management (elastic stockings). In a few,
      percutaneous sclerotherapy or partial excision of skin and muscle VMs was
      beneficial. Knee joint involvement required synovectomy and VM excision during
      childhood in 7 of 16 patients. CONCLUSION: Extensive limb VMs are characterized
      by diffuse involvement of the skin, muscle, and joints, and by a specific
      localized intravascular coagulopathy with general consequences. This group of
      vascular malformations should be separated from the Klippel-Trenaunay and Parkes
      Weber syndromes.

PMID- 9039173
TI  - Fluorescence photography in the evaluation of hyperpigmentation in photodamaged
      skin.
AB  - BACKGROUND: Treatment-related changes in hyperpigmentation are difficult to
      quantify with visible light photography, especially when the changes are subtle.
      OBJECTIVE: Our purpose was to determine the utility and reliability of
      fluorescence photography to measure changes in mottled and diffuse
      hyperpigmentation. METHODS: Thirty-two subjects, with mildly to moderately
      photodamaged skin, completed a 36-week, double-blind, vehicle-controlled study of
      tretinoin cream 0.025%. Clinical evaluation of hyperpigmentation as well as
      standard flash photographs and fluorescence photographs were obtained at baseline
      and week 36. RESULTS: The fluorescence photographs were evaluated blindly and
      yielded macule counts that decreased significantly from baseline in tretinoin
      treated subjects compared with vehicle-treated subjects (31% vs 11% decrease; p =
      0.02). Diffuse hyperpigmentation, as evaluated from the fluorescence photographs,
      decreased 16% from baseline for tretinoin-treated subjects and increased 5% for
      vehicle-treated subjects (p < 0.01). No significant differences in mottled or
      diffuse hyperpigmentation were observed between groups through clinical
      evaluation. CONCLUSION: Fluorescence photography is a noninvasive method that is
      sensitive in the evaluation and quantification of distribution and changes of
      mottled and diffuse hyperpigmentation.

PMID- 9039174
TI  - A multicenter, placebo-controlled, double-blind study of intermittent therapy
      with itraconazole for the treatment of onychomycosis of the fingernail.
AB  - BACKGROUND: Onychomycosis is the most frequent cause of nail disease and
      represents 30% of all mycotic infections of the skin. OBJECTIVE: Our purpose was
      to compare the effectiveness and tolerability of intermittent dosing of
      itraconazole ("pulse therapy") with placebo in fingernail onychomycosis. METHODS:
      Seventy-three patients with clinically and mycologically diagnosed fingernail
      onychomycosis were randomly selected to receive itraconazole, 200 mg twice daily,
      or placebo for the first week of each month for 2 consecutive months; patients
      were observed for 19 weeks. Seventy-one patients received the study medication
      and were included in the safety analysis. Efficacy of treatment was evaluated in
      46 patients. RESULTS: A significantly greater proportion of itraconazole-treated
      patients than placebo-treated patients achieved clinical success (77% vs 0%),
      mycologic success (73% vs 13%), and overall success (68% vs 0%). No itraconazole
      treated patient had a clinical or mycologic relapse during the follow-up period.
      Ten itraconazole-treated patients (28%) and nine placebo-treated patients (26%)
      had adverse events. Three patients discontinued treatment for safety reasons.
      CONCLUSION: Pulse therapy with itraconazole for 2 consecutive months produces
      significantly greater clinical, mycologic, and overall success than placebo.
      Short-term itraconazole pulse therapy for fingernail onychomycosis is effective
      and well tolerated.

PMID- 9039175
TI  - Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and
      isotretinoin.
AB  - BACKGROUND: Disseminated actinic keratoses are a therapeutic problem. OBJECTIVE:
      Our purpose was to evaluate the efficacy of a combination of topical 5
      fluorouracil twice a day and 20 mg of oral isotretinoin daily for disseminated
      actinic keratoses. METHODS: Twenty-seven patients who had disseminated actinic
      keratoses (3 women, 24 men) were treated with 5-fluorouracil (5%) twice a day
      applied to the photodamaged area bearing actinic keratoses along with oral
      isotretinoin, 20 mg daily. The median treatment time was 21 days. RESULTS:
      Actinic keratoses disappeared and signs of photodamaged skin improved in all
      patients. Side effects were burning and itching as well as painful erosions
      during the final stage of treatment. CONCLUSION: The combination of topical 5
      fluorouracil and isotretinoin is highly effective in the treatment of
      disseminated actinic keratoses on photodamaged skin.

PMID- 9039176
TI  - Hyaluronidase enhances the therapeutic effect of vinblastine in intralesional
      treatment of Kaposi's sarcoma. Military Medical Consortium for the Advancement of
      Retroviral Research (MMCARR).
AB  - BACKGROUND: Although intralesional vinblastine has been used with some success in
      the treatment of cutaneous lesions of Kaposi's sarcoma (KS), lesions commonly
      recur. When large lesions are treated, frequently there is considerable
      discomfort and, in some cases, secondary ulceration. Hyaluronidase has been used
      to increase dispersion of drugs administered by local injection. OBJECTIVE: Our
      purpose was to determine whether intralesional hyaluronidase administered before
      intralesional vinblastine increases the dispersion of vinblastine and decreases
      toxicity. METHODS: We treated six patients who had multiple cutaneous plaque
      lesions and tumors of KS with intralesional vinblastine, intralesional
      vinblastine preceded by intralesional hyaluronidase, or intralesional
      hyaluronidase alone. RESULTS: Both intralesional vinblastine and intralesional
      vinblastine preceded by intralesional hyaluronidase caused clinical regression of
      lesions of KS; however, the combination of hyaluronidase and vinblastine was more
      effective in treating tumor nodules. In addition, lesions treated with
      hyaluronidase and vinblastine recurred less often than those treated with
      vinblastine alone and showed no evidence of residual KS in two patients
      undergoing biopsy between 4 and 6 months after therapy. CONCLUSION: Intralesional
      hyaluronidase enhances vinblastine in the treatment of cutaneous lesions of KS
      without adding to the systemic toxicity.

PMID- 9039177
TI  - Insect repellents: an overview.
AB  - The optimal management of arthropod bites is prevention, and many over-the
      counter insect repellents are available. Since first marketed in 1956, deet has
      remained the most effective repellent against mosquitoes, biting fleas, gnats,
      and chiggers. Permethrin is applied to clothing rather than to skin, and it is a
      better repellent against ticks than deet. The risk of serious side effects with
      the use of deet is slight; nevertheless, the lowest effective concentration
      should be used. The current, popular repellent agents (for adults and children)
      and their active ingredients are discussed. In addition, the Environmental
      Protection Agency guidelines for the safe use of insect repellents are supplied.

PMID- 9039178
TI  - Patients' opinions regarding direct access to dermatologic specialty care.
AB  - Many factors such as cost have been used by managed care systems to limit patient
      access to specialty care, including dermatology. To date, however, patients'
      opinions regarding these decisions have not been analyzed. The purpose of the
      study was to survey patient opinions regarding the efficacy, costs, and
      desirability of gatekeeper-mediated versus direct access to dermatologic
      specialty care. One hundred fifteen of 150 consecutive patients who were seen in
      an outpatient dermatology clinic completed an anonymous survey concerning their
      current visit. They were asked about referral to the dermatologist by other
      physicians, number of prior physician visits, and efficacy of therapies received.
      Patients rated their level of satisfaction with generalist versus specialist care
      for their condition and evaluated the importance of direct access to dermatologic
      specialty care. Thirty-nine percent of respondents (42 of 108) were on their
      first visit to the dermatologist for their current condition. One half of
      respondents (57 of 115) had previously seen another physician for this condition.
      Thirty percent (34 of 115) had been referred to the dermatologist by another
      physician, most often a family practitioner or internist. Two thirds (38 of 57)
      of those seen by a previous physician had received therapy from that physician,
      but only one third (12 of 35) believed it to have been of any benefit. Twenty
      three percent (11 of 47) claimed to have incurred more than five visits to the
      other physician before seeing the dermatologist. Twenty-four percent of patients
      (12 of 50) were "very satisfied" with the previous physician's care compared with
      89% (100 of 112) with the dermatologist's care. Only 6% of respondents (7 of 122)
      believed a generalist could adequately treat their skin disease. Eighty-seven
      percent (100 of 115) described direct access to dermatology as being "very
      important" to their health care. The results of this study suggest that many
      patients may prefer dermatologic specialists over generalists as primary
      caregivers for diseases of the skin. They may favor direct access to dermatologic
      specialty care for its efficacy and for cost and time savings.

PMID- 9039179
TI  - Surgical pearl: preparing the defect for an island pedicle flap.

PMID- 9039180
TI  - Fixed drug eruption to three anticonvulsant drugs: an unusual case of
      polysensitivity.

PMID- 9039181
TI  - Cosmetically induced hair beads.

PMID- 9039182
TI  - Eruptive vellus hair cysts in a patient with ectodermal dysplasia.

PMID- 9039183
TI  - Correlation of skin disorders with CD4 lymphocyte counts in patients with
      HIV/AIDS.

PMID- 9039184
TI  - Long-term remission in selected patients with pemphigus vulgaris treated with
      cyclosporine.

PMID- 9039185
TI  - Allergic contact dermatitis from mupirocin ointment.

PMID- 9039186
TI  - Absence of human papillomavirus infection in cutaneous lichen planus.

PMID- 9039187
TI  - Acquired linear blue nevi.

PMID- 9039188
TI  - Inpatient dermatology: should we let it die or should we work towards regional
      centers?

PMID- 9039189
TI  - Treatment of hepatobiliary pruritus.

PMID- 9039190
TI  - Improvement of eumycetoma with itraconazole.

PMID- 9039191
TI  - Malignant melanoma in association with inflammatory skin metastasis.

PMID- 9039192
TI  - The role of allergy in the pathogenesis of atopic dermatitis.

PMID- 9039193
TI  - Nitric oxide release accounts for the reduced incidence of cutaneous infections
      in psoriasis.

PMID- 9039194
TI  - Epidemiologic case-control study in patients with vitiligo.

PMID- 9039195
TI  - Leishmaniasis.

PMID- 9039196
TI  - Pentoxifylline in recurrent aphthous stomatitis.

PMID- 9039197
TI  - Update on topical therapy for superficial fungal infections: focus on butenafine.

PMID- 9039198
TI  - Overview of topical therapy for common superficial fungal infections and the role
      of new topical agents.
AB  - Until recently the treatment options for superficial fungal infections have been
      limited mainly to the use of fungistatic drugs of the imidazole class, discovered
      in the 1960s. The recent development of allylamine and benzylamine compounds
      provides antifungal agents with fungicidal mechanisms of action. Both imidazole
      and allylamine/benzylamine drugs interfere with the production of ergosterol, an
      essential component of the fungal cell membrane; however, the newer drugs act at
      an earlier stage of the metabolic pathway than the azoles and cause an
      accumulation of squalene in the fungal cell, which leads to cell death. In vitro
      test results show that allylamine/benzylamine minimum inhibitory concentrations
      (MICs) and minimum fungicidal concentrations (MFCs) are lower than the MICs and
      MFCs of azoles tested by the same methods. In studies using animal models of
      dermatophytosis, results have shown the efficacy of the allylamine/benzylamine
      drugs to be superior to that of azole drugs. Clinical trials have also shown
      significant differences favoring allylamine/benzylamine drugs over imidazoles in
      the treatment of dermatophytosis. The fungicidal drugs provide earlier evidence
      of efficacy, higher cure rates with shorter treatment periods, and lower relapse
      rates than imidazoles in direct-comparison studies. The allylamine/benzylamine
      drugs have also shown high cure rates in patients with candidiasis.

PMID- 9039199
TI  - Treatment of interdigital tinea pedis with a 4-week once-daily regimen of
      butenafine hydrochloride 1% cream.
AB  - BACKGROUND: Butenafine hydrochloride, a potent new benzylamine with fungicidal
      activity, has been extensively studied and approved for topical use in Japan.
      Results reported here are from one of the first major North American butenafine
      clinical trials. OBJECTIVE: We evaluated butenafine in the treatment of tinea
      pedis in a controlled, randomized, double-blind trial. METHODS: Of 80 patients
      with positive fungal cultures, 40 applied butenafine 1% cream and 40 applied
      vehicle to the affected area once daily for 4 weeks. Efficacy was assessed during
      treatment and 4 weeks after. RESULTS: Significantly more patients using
      butenafine than using vehicle had mycologic cure (butenafine, 88%; vehicle, 33%)
      and effective clinical response (butenafine, 78%; vehicle, 35%). Differences
      between treatment groups were greatest (p < 0.001) 4 weeks after treatment.
      CONCLUSION: Butenafine applied once daily for 4 weeks resulted in an effective
      clinical response and mycologic cure of tinea pedis during treatment. Patients
      continued to improve for at least 4 weeks after treatment.

PMID- 9039200
TI  - One-week therapy with twice-daily butenafine 1% cream versus vehicle in the
      treatment of tinea pedis: a multicenter, double-blind trial.
AB  - BACKGROUND: Butenafine hydrochloride, a benzylamine derivative with potent
      antifungal activity, has been used in Japan to treat superficial fungal diseases.
      OBJECTIVE: We evaluated the safety and efficacy of twice-daily butenafine versus
      its vehicle in the treatment of interdigital tinea pedis in a multicenter,
      randomized, double-blind, parallel-group trial. METHODS: A total of 402 patients
      with interdigital tinea pedis and a positive potassium hydroxide examination were
      enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were
      assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily
      for 1 week. Patients were assessed for mycologic cure, effective treatment,
      overall cure, and mycologic/clinical cure. RESULTS: The rates of all four end
      points were significantly higher with butenafine than with vehicle 5 weeks after
      treatment ended. Rates of mycologic cure and effective treatment with butenafine
      were significantly higher than with vehicle at cessation of treatment. Adverse
      events to treatment occurred in less than 1% of patients treated with butenafine
      and 2% of patients who applied vehicle. CONCLUSION: Butenafine applied twice
      daily for 1 week is highly effective in treating interdigital tinea pedis.

PMID- 9039201
TI  - Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehicle
      controlled, double-blind trial.
AB  - BACKGROUND: Butenafine hydrochloride, a potent antifungal agent related to the
      allylamines, has been used in Japan for treating various cutaneous mycoses
      including tinea cruris. OBJECTIVE: We compared the safety and efficacy of
      butenafine hydrochloride and its vehicle when used once daily for 2 weeks to
      treat tinea cruris. METHODS: Patients (n = 93) with tinea cruris and a positive
      potassium hydroxide examination and mycologic culture were enrolled. Of the 76
      patients assessed for efficacy, 37 applied butenafine and 39 applied vehicle once
      daily for 2 weeks. Assessments were made at the end of the 2-week treatment
      period and 4 weeks after the end of treatment. RESULTS: Patients in the
      butenafine group had a higher mycologic cure rate by day 7 (66% vs 13%, p <
      0.0001), with marked improvement 4 weeks after the end of treatment (81% vs 13%,
      p < 0.0001). They also had a higher rate of effective treatment at day 7 (29% vs
      5%, p < 0.01) and at 4 weeks after treatment (73% vs 5%, p < 0.0001). Adverse
      events definitely related to butenafine treatment were limited to one case of
      burning sensation after application. CONCLUSION: Butenafine applied once daily
      for 2 weeks is effective in treating tinea cruris. The proportion of patients
      cured increased between the end of treatment and 4 weeks after treatment.

PMID- 9039202
TI  - Subcutaneous T-cell lymphoma.
AB  - We describe a patient with severe fatal histiocytic phagocytic panniculitis
      caused by a pleomorphic T-cell lymphoma. Analysis by polymerase chain reaction
      revealed clonality for both the T-cell receptor gamma-chain gene and the
      immunoglobulin heavy-chain gene. We also review 44 reported cases of primary or
      secondary lymphoma affecting the subcutaneous fat.

PMID- 9039203
TI  - Cutaneous involvement in prelymphomatous angioimmunoblastic lymphadenopathy.
AB  - We describe prelymphomatous angioimmunoblastic lymphadenopathy with cutaneous
      involvement in a 73-year-old female patient. A maculopapular skin eruption was
      the first sign of the disease. Skin histology showed extensive perivascular and
      periadnexal mixed lymphoid infiltrates including centroblasts and immunoblasts
      with a high proliferative index and with focal erythrocyte extravasation. Lymph
      node histology confirmed the diagnosis, showing nearly complete effacement of the
      follicular architecture, a mixed lymphoid infiltrate, and numberous high
      endothelial venules in an expanded T-cell zone. Immunohistochemistry, however,
      demonstrated preservation of at least some follicular structures. T-cell receptor
      gene rearrangement analysis revealed oligoclonal patterns in both lymph node and
      skin specimens. In contrast, immunoglobulin heavy-chain gene rearrangement
      analysis revealed a polyclonal pattern. Accordingly, the disease was classified
      as a prelymphomatous stage of angioimmunoblastic lymphadenopathy with
      dysproteinemia (AILD) with specific involvement of both lymph node and skin. The
      patient was treated with high-dose corticosteroids, and long-lasting remission
      was induced. In contrast to our case, most reported cases of AILD show a
      monoclonal T-cell pattern indicating AILD-type lymphoma. Therefore we discuss the
      concept of prelymphomatous AILD developing into AILD-type lymphoma. Persistence
      of some antigenic stimulus may induce the proliferation of a monoclonal
      population of lymphoid cells from a polyclonal background in a multistep fashion.
      Proper treatment of AILD at an early, prelymphomatous stage may protract or
      inhibit development of full-blown, fatal AILD-type lymphoma.

PMID- 9039204
TI  - The importance of early diagnosis in multiple endocrine neoplasia III: report of
      a case with thyroid C-cell hyperplasia.
AB  - Multiple endocrine neoplasia III (MEN III), also known as MEN IIb or mucosal
      neuroma syndrome, can often be recognized at an early age by its typical facies,
      marfanoid habitus, and characteristic mucosal neuromas. These features are
      usually present before development of the more serious, life-threatening
      complications that consist of medullary thyroid carcinoma (MTC) and
      pheochromocytoma. MTC associated with MEN III is generally aggressive with early
      metastasis. Early diagnosis is therefore crucial so that patients can be
      appropriately monitored for thyroid cancer with prompt thyroidectomy when
      indicated. Occasionally, patients present with C-cell hyperplasia of the thyroid,
      the histologic precursor to MTC. We describe a 16-year-old boy with mucosal
      neuromas, the typical facies of MEN III, gastrointestinal ganglioneuromatosis,
      and C-cell hyperplasia of the thyroid gland. Prompt thyroidectomy was performed,
      averting the risk of malignant transformation. Early clinical recognition of MEN
      III is crucial, as timely intervention can prevent the high mortality associated
      with MTC and pheochromocytoma.

PMID- 9039205
TI  - Linear focal elastosis: a review of three cases in young Japanese men.
AB  - Linear focal elastosis in three young Japanese men is described. The lesions are
      asymptomatic palpable yellow strialike bands extending horizontally across the
      middle and lower parts of the back. They are histologically composed of many fine
      wavy bundles of elastic fibers separating the dermal collagen bundles. Electron
      microscopy demonstrates numerous elongated and fragmented elastic fibers.

PMID- 9039206
TI  - Gastric outlet obstruction and epidermolysis bullosa.
AB  - We describe a case of pyloric atresia coexisting with epidermolysis bullosa,
      almost certainly of the junctional type. The coexistence of pyloric atresia and
      junctional epidermolysis bullosa (PA-JEB syndrome) has been repeatedly observed.
      This syndrome has several clinical features that distinguish it from Herlitz
      junctional epidermolysis bullosa (JEB). These include a lack of prominent
      granulation tissue formation and increased frequencies of genitourinary tract
      involvement and ear anomalies. Aplasia cutis congenita is sometimes present;
      esophageal atresia is uncommonly present. In all 12 patients examined to date,
      normal basement membrane zone expression of laminin-5 biochemically distinguishes
      PA-JEB syndrome from Herlitz JEB. Mutations in the beta 4 integrin gene have been
      observed in one patient with PA-JEB syndrome. Thus there are both clinical and
      biochemical reasons to separate the PA-JEB syndrome from Herlitz JEB. This is the
      second known case of papillary hyperplasia of the amnion to be seen in any
      setting. The other was a case of JEB without pyloric atresia.

PMID- 9039207
TI  - Borrelia burgdorferi-associated primary cutaneous B cell lymphoma: complete
      clearing of skin lesions after antibiotic pulse therapy or intralesional
      injection of interferon alfa-2a.
AB  - We report two patients with low-grade malignant primary cutaneous B cell lymphoma
      in association with Borrelia burgdorferi infection. Extracutaneous manifestations
      were ruled out by standard staging procedures. Infection with Borrelia
      burgdorferi was confirmed by cultivation from lesional skin in both patients. In
      the first patient skin lesions cleared completely after pulse therapy with
      cefotaxime, whereas in the second patient antibiotic treatment failed. In this
      patient, however, skin lesions completely cleared after intralesional injection
      of interferon alfa-2a. Antibiotic treatment or intralesional injection of
      interferon alfa-2a should be considered as a first-line treatment of Borrelia
      burgdorferi-associated primary cutaneous B cell lymphoma before more aggressive
      conventional therapeutic modalities (e.g., radiation therapy) are applied.

PMID- 9039208
TI  - The efficacy of dermabrasion in the treatment of nodular amyloidosis.
AB  - Nodular amyloidosis is a rare entity that predominantly affects females in the
      sixth and seventh decades. Frequent cutaneous sites of involvement are the
      extremities, trunk, and genitalia. Numerous cosmetic procedures have been
      employed to treat the lesions of nodular amyloidosis. Dermabrasion, which was
      performed on the lesions of nodular amyloidosis on the chin after surgical
      debulking, proved successful in the treatment of localized nodular amyloidosis.
      Follow-up at 26 months showed no clinical evidence of recurrence. Dermabrasion
      offers another acceptable modality for cosmetic treatment of nodular amyloidosis.

PMID- 9039209
TI  - Lesions resembling malignant atrophic papulosis in a patient with
      dermatomyositis.
AB  - Many consider porcelain white atrophic papules as pathognomonic for malignant
      atrophic papulosis (MAP), or Degos' disease. During the past three decades, five
      patients with a collagen vascular disease have been reported to have MAP-like
      lesions as a manifestation of their underlying illness. We describe a patient
      with dermatomyositis who had porcelain-white atrophic papules resembling
      malignant atrophic papulosis.

PMID- 9039210
TI  - Nonscarring inflammatory epidermolysis bullosa acquisita with esophageal
      involvement and linear IgG deposits.
AB  - A 24-year-old woman with autoimmune thrombocytopenia and hypothyroidism had an
      inflammatory bullous eruption in the mouth, face, and trunk that left no milia or
      scars after healing. Histologic examination revealed a subepidermal bulla and a
      neutrophil infiltration. Direct immunofluorescence examination showed deposition
      of IgG and C3 in the basement membrane zone (BMZ). Indirect immunofluorescence
      examination with 1M sodium chloride-split skin showed IgG binding to the dermal
      side. Immunoblot analysis demonstrated IgG autoantibodies reacting with 290 kD
      dermal protein. We diagnosed this as epidermolysis bullosa acquisita (EBA) with a
      nonscarring inflammatory feature. Treatment with oral dapsone, 75 mg, and
      prednisolone, 20 mg, cleared the eruption. Reduction of the prednisolone dosage
      was associated with multiple erosions in the esophagus. Direct immunofluorescence
      examination revealed linear deposition of IgG in the esophageal BMZ. To our
      knowledge, this is the first report of EBA with esophageal involvement and
      deposition of IgG in the BMZ of the esophagus.

PMID- 9039211
TI  - Mucinous carcinoma of the skin.
AB  - Primary mucinous carcinoma of the skin is a rare adnexal neoplasm with sweat
      gland differentiation. We describe a case of primary mucinous carcinoma of the
      skin and characterize its clinical and histologic features. Mucinous carcinoma
      can occur in noncutaneous visceral sites and may metastasize to the skin. Thus it
      is important to exclude the possibility of a noncutaneous visceral primary tumor
      before diagnosing primary mucinous carcinoma of the skin.

PMID- 9039212
TI  - Multiple cutaneous granular cell tumors in a child with possible
      neurofibromatosis.
AB  - A 4-year-old girl with possible neurofibromatosis I had multiple subcutaneous
      nodules. On histopathologic examination, these nodules were diagnosed as multiple
      cutaneous granular cell tumors. An association between these tumors and
      neurofibromatosis I has been suggested because of their common neuroectodermal
      origin. We review cases of multiple cutaneous granular cell tumors in association
      with neurofibromatosis I in childhood.

PMID- 9039213
TI  - Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa
      acquisita.
AB  - Epidermolysis bullosa acquisita is an uncommon autoimmune bullous disease of the
      skin and mucous membranes. It is chronic, disabling, and difficult to treat. We
      describe a case of severe epidermolysis bullosa acquisita of 7 years' duration
      that had been treated with azathioprine, corticosteroids, chlorambucil, plasma
      exchanges, cyclophosphamide, cyclosporine, and colchicine without any lasting
      effect. Seven cycles of treatment were administered with immunoglobulin given
      intravenously at a low dose, 40 mg/kg body weight daily for 5 days. The patient
      was free of disease for 10 months after the initiation of therapy. We suggest
      that low-dose regimens of immunoglobulins may be as effective in this disease as
      the high-dose regimens suggested in the literature, and at much lower cost.

PMID- 9039214
TI  - Cutaneous mucormycosis with subsequent visceral dissemination in a child with
      neutropenia: a case report and review of the pediatric literature.
AB  - Primary cutaneous mucormycosis is a rare opportunistic fungal infection that is
      usually limited to the skin. We describe a primary cutaneous Rhizopus infection
      occurring at a site occluded by a sterile adhesive dressing in which the disease
      was viscerally disseminated at the time fo diagnosis. Mucormycosis should be
      considered in all ecthyma-like lesions in immunocompromised patients. It may be
      rapidly diagnosed by examination of hematoxylin-eosin and PAS-stained sections of
      the eschar base and a culture of a leading edge tissue aspirate. We review 21
      cases of primary cutaneous mucormycosis in children and compare them with the
      present case.

PMID- 9039215
TI  - EBV-associated Kikuchi's histiocytic necrotizing lymphadenitis with cutaneous
      manifestations.
AB  - The clinical and pathologic findings of Kikuchi's histiocytic necrotizing
      lymphadenitis may mimic those of malignant lymphoma. We describe a 6-year-old boy
      with generalized lymphadenopathy, spiking fever, chills, myalgias, malaise, and
      erythematous, crusted papules. Although cutaneous manifestations have been noted
      in 16% to 40% of patients with histiocytic necrotizing lymphadenitis, only three
      publications described skin lesions. The skin lesions and affected lymph nodes
      revealed histiocytic aggregates, atypical lymphoid cells, karyorrhectic debris,
      and patchy necrosis. Spontaneous resolution occurred in 2 months. Results of
      serologic studies, Epstein-Barr virus (EBV) latent membrane protein
      immunoperoxidase staining, EBER-1 RNA in-situ hybridization, and EBV EBNA-1 DNA
      polymerase chain reaction implicate EBV as the causative agent.

PMID- 9039216
TI  - Fever, lymphadenopathy, eosinophilia, lymphocytosis, hepatitis, and dermatitis: a
      severe adverse reaction to minocycline.
AB  - A 17-year-old female patient who had been taking oral minocycline (50 mg twice
      daily) for 3 weeks for acne developed an eruption that progressed to an
      exfoliative dermatitis. This illness was also characterized by fever,
      lymphadenopathy, pharyngitis, a leukemoid reaction, lymphocytosis, eosinophilia,
      hepatitis, and noncardiogenic pulmonary edema. Dramatic improvement followed
      institution of corticosteroid therapy. Studies for infectious and collagen
      vascular diseases were negative. This severe illness was likely caused by
      minocycline, and we speculate that minocycline may have acted as a superantigen,
      causing lymphocyte over-activation and massive cytokine release.

PMID- 9039217
TI  - Congenital syphilis: subtle presentation of fulminant disease.
AB  - The incidence of congenital syphilis has experienced a fourfold to fivefold
      increase in 6 years. It is a completely preventable disease whose clinical
      spectrum ranges from asymptomatic infection, to fulminant sepsis, to death.
      Congenital syphilis was diagnosed in a 6-week-old infant whose mother was
      negative for the disease by prenatal screen. The otherwise well child presented
      with a generalized, papulosquamous eruption of 3 weeks' duration but within hours
      multisystem failure developed from overwhelming treponemal sepsis. Factors
      related to increased incidence, problems in serodiagnosis, manifestations of the
      early versus late forms of the disease, and recommendations for evaluation and
      treatment are illustrated by this patient and are discussed.

PMID- 9039218
TI  - Mutagen sensitivity: enhanced risk assessment of squamous cell carcinoma.

PMID- 9039219
TI  - Efficacy of vitamin A in the prevention of loco-regional recurrence and second
      primaries in head and neck cancer.
AB  - Chemoprevention with retinoids is currently an experimental approach to prevent
      local relapses and second primaries in treated head and neck cancer patients. We
      evaluated the effectiveness of vitamin A in preventing the above events in a
      randomised trial involving 106 head and neck cancer patients who had achieved
      complete regression of their disease with radiotherapy and/or surgery. They were
      randomised to receive retinyl palmitate (200,000 IU per week for 1 year) or
      placebo. 50 subjects on vitamin A and 43 on placebo completed 1 year
      supplementation; 49 in the former group and 42 in the latter could be evaluated
      over a 3 year period from the initiation of the study. One fifth (11/56) of
      patients in the vitamin A group and one tenth (5/50) in the placebo group had
      loco-regional recurrence. The frequency of recurrences in stage I patients in the
      vitamin A group was higher compared to the placebo group, although it was not
      statistically significant. No second primaries were observed in the vitamin A
      group; 2 patients in the placebo group had second primaries. No clinically
      obvious side effects were observed with vitamin A. The higher frequency of
      recurrences in the vitamin A group is of concern although it may be a chance
      finding given the small size of the trial. The effect on second primaries is
      consistent with other observations reported in literature.

PMID- 9039220
TI  - Serum levels of CYFRA 21-1 in nasopharyngeal carcinoma and its possible role in
      monitoring of therapy.
AB  - CYFRA 21-1 is a fragment of cytokeratin expressed by simple epithelia and their
      malignant counter-parts. Serum CYFRA 21-1 levels were studied in 240 new cases of
      nasopharyngeal carcinoma and 19 patients who developed distant metastases. A
      reference range of < 2 U/ml for our local Chinese population was established in
      55 sex- and age-matched healthy volunteers. The nasopharyngeal carcinoma patients
      had significantly higher marker levels than the healthy controls and the mean
      level increased with advancing stage. However, the low percentage of elevation in
      early stages means that the marker is not useful for screening. The overall
      percentage (52.5) of elevation in 240 newly diagnosed squamous cell carcinoma of
      the nasopharynx is comparable to that of squamous cell carcinoma of the lungs,
      suggesting that the expression of CYFRA 21-1 is related to the cell type rather
      than the tissue type of the carcinoma, 46 (95.8%) of 48 patients with metastatic
      nasopharyngeal carcinoma showed an elevated value of CYFRA 21-1. This extremely
      high percentage implies that it is very unlikely for a patient with a normal
      value to have distant metastasis. This may permit major economies in radiological
      screening for distant metastasis. Preliminary results from serial measurement of
      the marker indicated its potential for monitoring response to treatment and for
      early detection of distant metastasis.

PMID- 9039221
TI  - Quantitative scale of oral mucositis associated with autologous bone marrow
      transplantation.
AB  - Acute oral complications are serious and disabling secondary effects for patients
      undergoing cancer therapy. Therefore, the authors wanted to develop a sensitive
      and specific method to measure oral mucosal changes associated with autologous
      with autologous bone marrow transplantation. 14 patients, all volunteers, 18-56
      years old, receiving conditioning regimens of cyclophosphamide and total body
      irradiation were included. The clinical changes of the oral mucosa and functional
      modifications were scored daily, over 21 days with a 16 item scale, ranging from
      0 to 3. A daily index of mucositis (DIM) was established by adding the scores
      obtained for the 16 items and a cumulative score of oral mucositis was obtained
      by the addition of the 21 DIM for assessing the severity of oral mucositis
      throughout its duration. The internal consistency measures (Chronbach alpha) were
      strong (range 0.80-0.97). A scale of equivalence, pre-established in comparison
      with pre-existing general mucositis rating scales, permitted a day by day simple
      classification in a 4-grade scale, to be obtained. Support for the validity of
      the suggested scale is presented. This scale may help to improve the study of
      oral complications of cancer therapy.

PMID- 9039222
TI  - Discordance of p53 status in matched primary tumours and metastases in head and
      neck squamous cell carcinoma patients.
AB  - To study the use of p53 as a diagnostic tool in head and neck squamous cell
      carcinoma (HNSCC), we analysed 15 primary tumours (PT) and matched lymph node
      metastases (LNM) for overexpression and mutations of p53. The primary goal was to
      study whether differentiation between primary and metastatic disease through
      their p53 status would be possible. Immunohistochemistry for p53 protein
      (antibody BP 53-12-1) was performed. Mutations of the p53 gene were detected by
      exon-specific amplification of DNA (exons 4-9), followed by exon analysis using
      denaturing gradient gel electrophoresis (DGGE). Mutant exons were sequenced. p53
      overexpression was detected in seven (47%) of the PT and in seven (47%) of the
      LNM. 6 patients (40%) exhibited p53 protein overexpression in both PT and LNM. 2
      patients had a different p53 protein expression in each sample. Mutations in the
      p53 gene were detected in 6 patients (40%) in the PT and in 7 patients (47%) in
      the LNM. In 2 patients (13%), the same mutation was found in the PT and in the
      LNM. 9 patients (60%) had a different mutation in each sample. We conclude that a
      poor correlation exists between p53 protein overexpression and p53 gene mutation
      in HNSCC. Also, a poor correlation for both detection techniques exists, when PT
      and LNM are compared. The p53 status may seem to differ between PT and LNM
      because of polyclonality in the PT. More sensitive detection techniques could be
      promising.

PMID- 9039223
TI  - Differential expression of bcl-2 and bax in squamous cell carcinomas of the oral
      cavity.
AB  - The bcl-2 oncogene is a member of a family of genes encoding for proteins which
      regulate apoptosis (programmed cell death). Recent evidence suggests that the bcl
      2 protein is regulated by a homologous protein bax which counteracts its effects
      and promotes apoptosis. Overexpression of bcl-2 has been reported in a number of
      human cancers, although correlations with tumour differentiation and clinical
      outcome are conflicting and depend on tumour type and site. We studied bcl-2 and
      bax protein expression in adjacent serial sections of 30 squamous cell carcinomas
      of the oral cavity and correlated this with tumour differentiation. Examination
      of normal epithelium showed bcl-2 expression confined to basal keratinocytes and
      dendritic cells. The bax immunostaining was seen throughout the thickness of the
      epithelium but was most intense in the suprabasal cells. Overall, moderate or
      marked immunostaining for bcl-2 was identified in 18/30 (60%) carcinomas and for
      bax in 19/30 (63%) tumours. The bcl-2 immunoreactivity was strongest in the
      poorly differentiated carcinomas where 6/7 (86%) showed strong staining. By
      contrast, bax immunoreactivity was strongest in the well-differentiated
      carcinomas with 8/11 (72%) staining strongly. In the well-differentiated tumour
      islands, there was inverse topographic distribution of bcl-2 and bax, with both
      proteins showing a pattern that recapitulated normal epithelium. Upregulation of
      bcl-2 protein was identified in dysplastic epithelium adjacent to invasive tumour
      and in many cases there was reduced bax immunostaining. These results suggest
      that alterations of bcl-2 and bax may play a role in the development of squamous
      cell carcinoma. Furthermore, disturbances of protein expression in dysplastic
      epithelium suggest a role in the early stages of epithelial carcinogenesis.

PMID- 9039224
TI  - Immunohistochemical evaluation of transglutaminase C in tumours of salivary
      glands.
AB  - Transglutaminase C (TGase C), a family of Ca(2+)-dependent enzymes and an
      essential component in the cross-linking of peptide bonds, has been found to be a
      marker of epithelial differentiation with a possible role in cellular apoptosis,
      extracellular matrix stabilisation and Ca2+ binding, thereby having a potential
      role in tumour growth, differentiation and invasive behaviour. The expression of
      TGase C was evaluated in normal human salivary glands and their neoplastic
      lesions which included pleomorphic adenoma (n = 30), Warthin's tumour (n = 5),
      adenoid cystic carcinoma (n = 10), acinic cell carcinoma (n = 5), mucoepidermoid
      carcinoma (n = 5) and control tissue specimens of normal oral mucosa and squamous
      cell carcinoma, using polyclonal antibody, the specificity of which was
      determined by Western blotting, generated by immunising rabbits with purified
      transglutaminase. The TGase C was observed in the epithelial cells in the control
      tissue specimens examined. Pleiomorphic adenoma revealed reaction products in
      luminal tumour cells, the non-luminal or modified myoepithelial cells and their
      plasmacytoid variants, squamous metaplastic cells and chondroid cells. Adenoid
      cystic carcinomas had tumour cells in the luminal cells of tubular and cribriform
      structures and the acinic cell carcinoma had from low to moderate
      immunoreactivity in the tumour cell component and a diffuse immunoreactivity in
      the stroma for TGase C. Mucoepidermoid carcinoma showed no reaction products in
      the mucous-producing cells, while intermediate and epidermoid cells had
      immunoreactivity in the cell cytoplasm. As the presence of TGase C in salivary
      gland tumours was confined to those tumour cells which form the predominant
      histomorphology in each tumour subtype, it may be suggested that these enzymes
      may have a potential role in the regulation of cellular function in neoplastic
      salivary tissues affecting tumour growth, differentiation and neoplastic
      behaviour.

PMID- 9039225
TI  - Major glossectomy: end results of 106 cases.
AB  - Advanced cancers of the oral cavity continue to be a therapeutic challenge.
      Despite significant improvements in radiotherapeutic techniques and adjuvant
      chemotherapy, patients usually die after a short period. Recent progress in
      reconstructive techniques has made major glossectomy (subtotal, near total, total
      or extended total) a reasonable palliative and potentially curative approach. It
      is the purpose of this study to report a series of 106 patients treated from 1985
      to 1994 regarding surgical complications and prognosis. All but 1 patient
      undergoing major glossectomy had squamous cell carcinoma. Primary tumour sites
      were oral tongue (50 cases), base of the tongue (18 cases), floor of the mouth
      (28 cases) and other parts of the mouth (10 cases). Tumour stages were: 25 T3, 57
      T4, 24 Tx, 34 N0, 20 N1, 32 N2a-N3, 20 Nx. The types of glossectomy were as
      follows: 24 subtotal, 31 near total and 51 total. A total laryngectomy was
      performed in only 6 cases. A neck dissection was performed in all but 3 patients:
      12 unilateral radical neck dissection (RND), 1 unilateral supra, omohyoid (SOH),
      39 simultaneous bilateral RND, 8 simultaneous bilateral SOH, and 43 RND
      associated to contralateral SOH. A pectoralis major myocutaneous flap was used to
      repair the operative defect in 96 cases. Complications were seen in 52 cases
      (49%). The most common complications were wound infection (17 cases), flap
      necrosis (15 cases) and fistula (15 cases). Significant transient aspiration was
      seen in 8 patients. At the study closing date, 30 patients were alive without
      disease, 5 had recurrent disease, 47 died of cancer, 14 died of causes not
      related to cancer or treatment and 10 were lost to follow-up. The 5-year
      actuarial survival rates were, respectively, 45%, 18% and 18% for T3, T4 and Tx.
      Other significant variables were pN stage (P = 0.0672) and year of admission
      (0.0318). In conclusion a major glossectomy without laryngectomy whenever
      possible is a safe procedure for a selected group of patients with advanced
      tongue and floor of the mouth cancer. The actuarial survival rates presented
      suggests that, in a very select group of patients, major glossectomy is a
      surgical procedure to be considered.

PMID- 9039226
TI  - Autopsy findings in patients with head and neck squamous cell cancer and their
      therapeutic relevance.
AB  - A series of 63 autopsied patients with a history of head and neck squamous cell
      cancer (HNSCC) is reported with emphasis on the importance of locoregional
      disease (LRD) versus distant metastasis (DM) in the terminal course of the
      disease. There were 49 males and 14 females; mean age 64.9 years (range 35-94
      years). Locoregional disease was present in 39 patients (62%), in 25 (40%)
      without tumour at other body sites outside the head and neck region. Distant
      metastasis was observed in 15 patients (24%); in 12 (19%), it occurred with
      concomitant LRD. Second primary tumours (SPT) were observed in 20 patients (32%).
      They occurred in the head and neck region (n = 7; 11%), the lung (n = 9; 14%) and
      at miscellaneous other sites (n = 4; 6%). Of the 13 patients with SPT outside the
      head and neck region, 2 had concomitant LRD. 11 patients (17%) died due to other
      causes, no tumour being found at autopsy. These figures indicate that still a
      major part of HNSCC patients die with LRD as the single tumour manifestation,
      which means that improvement of local tumour control will result in a significant
      therapeutic gain.

PMID- 9039227
TI  - Prevalence study of oral white lesions with special reference to a new definition
      of oral leucoplakia.
AB  - In this survey, the experiences with and implications of a revised definition of
      oral leucoplakia are described. One of the new aspects of the revised definition
      is the distinction between a provisional, clinical diagnosis and a definitive one
      for which histopathological examination is required. A prevalence study of white
      lesions of the oral mucosa among a selected population of 1000 consecutive
      patients from the Netherlands showed a prevalence of a provisional and definitive
      diagnosis of oral leucoplakia of 0.6 and 0.2%, respectively. For uniform
      reporting, a recently proposed classification and staging system has been used to
      stage leucoplakias with a definitive diagnosis. The use of the revised definition
      of oral leucoplakia, as well as the classification and staging system, seem very
      suitable for epidemiological studies.

PMID- 9039228
TI  - Marginal zone B cell lymphoma of the parotid glands: results of a randomised
      trial comparing radiotherapy to combined therapy.
AB  - 39 patients with marginal zone B cell lymphoma (MZBCL) of the parotid glands
      (stages I or II) were studied. They were randomized to be treated with either
      radiotherapy alone (extended fields, 4500 cGy) or radiotherapy (the same
      schedule) plus adjuvant chemotherapy (cyclophosphamide, vincristine and
      prednisone). The end points were survival and time to treatment failure (TTF).
      Patients who received radiotherapy alone had a complete remission rate of 100%,
      the TTF was 90% at 5 years and overall survival at 5 years was 90% with no
      statistical difference when compared with patients who received combined therapy
      [100, 80 and 95%, respectively (P = 0.5)]. Although adjuvant chemotherapy was
      well tolerated, the use of this therapeutic approach in patients with early stage
      MZBCL did not offer any advantage over radiotherapy alone as the initial
      treatment. Until now, radiotherapy was considered the treatment of choice in this
      clinical setting of patients.

PMID- 9039229
TI  - Desmoplastic malignant melanoma of the gingiva: case report and review of the
      literature.
AB  - A rare case of desmoplastic melanoma arising from the maxillary gingiva of a 66
      year-old woman is reported. This tumour metastasised to the submandibular lymph
      node 5 years after extirpation, and local recurrence was observed 2 years later.
      The gingival tumour showed the histopathological characteristics of desmoplastic
      melanoma and the metastasised tumour cells were immunohistochemically positive
      for S-100 protein, neuron specific enolase, HMB-45 highly specific for
      conventional melanoma, and Fontana-Masson staining. The gingival tumour,
      originally regarded as benign clinically, was actually a desmoplastic melanoma.

PMID- 9039230
TI  - Allergic respiratory disease: strategic targets for primary prevention during
      childhood.

PMID- 9039231
TI  - Laser assisted uvulopalatoplasty in sleep disordered breathing.

PMID- 9039232
TI  - Making measurements in the pulmonary circulation: when and how?

PMID- 9039233
TI  - Expression of bcl-2 and Epstein-Barr virus LMP1 in lymphocytic interstitial
      pneumonia.
AB  - BACKGROUND: Epstein-Barr virus (EBV) genome has been demonstrated in lung tissues
      of patients with lymphocytic interstitial pneumonia (LIP) but its role in the
      pathogenesis of this condition is unclear. In vitro studies have shown that EBV
      can immortalise and transform cells by upregulation of the cellular proto
      oncogene, B cell leukaemia-2 (bcl-2), via the viral latent membrane protein,
      LMP1. The purpose of this study was to determine whether bcl-2 expression is
      upregulated in the lungs of patients with LIP and whether EBV LMP1 has a role in
      this bcl-2 expression. METHODS: Immunohistochemical analysis using alkaline
      phosphatase anti-alkaline phosphatase (APAAP) was performed on formalin fixed,
      paraffin embedded lung tissues from 13 patients with LIP using anti-LMP1 and anti
      bcl-2 monoclonal antibodies. Lung tissues from nine patients with idiopathic
      pulmonary fibrosis (IPF) and nine necropsy cases without pulmonary disease served
      as controls. LMP1 positivity was estimated as the number of LMP1 positive cells
      per unit area of lung tissue. Immunostaining for bcl-2 expression was assessed by
      a pictorial-based semiquantitative grading system. RESULTS: Positive
      immunostaining for LMP1 was localised to airway epithelial cells of lung tissue.
      Ten out of 13 (77%) patients with LIP were positive for LMP1 compared with three
      of nine cases (33%) in each control group. LMP1 positivity of LIP cases was
      significantly greater than that of non-LIP cases: LIP versus IPF (mean
      difference, 95% confidence interval (CI)) 2.39 (1.54 to 3.24); LIP versus
      necropsy controls 2.62 (1.77 to 3.47). bcl-2 immunostaining was localised to
      lymphocytes within the alveolar septa and lymphoid aggregates of patients with
      LIP. The cumulative score for bcl-2 immunostaining was significantly higher in
      the lungs of patients with LIP than in those of patients with IPF and necropsy
      controls: LIP versus IPF and LIP versus necropsy controls (mean difference, 95%
      CI) 7.55 (7.18 to 7.92). CONCLUSIONS: These immunohistochemical studies have
      shown the presence of EBV LMP1 protein in airway epithelial cells and
      overexpression of the cellular bcl-2 protein in lymphoid cells of lung tissue in
      patients with LIP. These geographically distinct staining patterns of
      immunostaining suggest that the involvement of EBV LMP1 in the upregulation of
      cellular bcl-2 is more complex in LIP than was thought from previous in vitro
      observations. The respective roles of EBV LMP1 and bcl-2 in the pathogenesis of
      LIP require further studies.

PMID- 9039235
TI  - Chronic bronchitis in textile workers.
AB  - BACKGROUND: Exposure to cotton is known to produce a specific occupational
      disease known as byssinosis. A large population of textile workers was
      investigated to determine whether such exposure was also associated with chronic
      bronchitis once other possible aetiological factors had been accounted for.
      METHODS: A total of 2991 workers were investigated for the presence of symptoms
      compatible with chronic bronchitis. An MRC adapted respiratory questionnaire and
      MRC definition of chronic bronchitis were used for diagnostic labelling. Current
      and lifetime exposure to dust was estimated by personal and work area sampling,
      and the use of records of retrospective dust levels previously measured over the
      preceding 10 years. Airborne endotoxin exposure was measured using a quantitative
      turbidometric assay. Lung function tests were performed to measure forced
      expiratory volume in one second (FEV1) and forced vital capacity (FVC). A control
      group of workers exposed to man-made fibre textiles was identified. The
      comparative prevalence of chronic bronchitis in the two populations was assessed,
      allowing for sex, age, smoking habit, and ethnic origin. Two case referent
      studies were also performed; cases of chronic bronchitis were separately matched
      with controls from the cotton and control populations to determine the effect of
      the symptomatic state on lung function. RESULTS: After controlling for smoking
      (pack years), workers in a cotton environment were significantly more likely to
      suffer from chronic bronchitis and this was most marked in workers over 45 years
      of age (odds ratio 2.51 (CI 1.3 to 4.9); p < 0.01). Regression analysis of all
      possible influencing parameters showed that cumulative exposure to cotton dust
      was significantly associated with chronic bronchitis after the effects of age,
      sex, smoking, and ethnic group were accounted for (p < 0.0005). In the intra
      cotton population case control study a diagnosis of chronic bronchitis was
      associated with a small decrement in lung function compared with controls:
      percentage predicted FEV1 in cases 81.4% (95% CI 78.3 to 84.6), controls 86.7%
      (84.9 to 88.5); FVC in cases 89.9% (95% CI 87.0 to 92.9), controls 94.6% (92.8 to
      96.4). After controlling for cumulative past exposure and pack years of smoking
      the effect of the diagnostic state remained significant for both FEV1 (p < 0.01)
      and FVC (p < 0.05). CONCLUSIONS: Chronic bronchitis is more prevalent in cotton
      workers than in those working with man-made fibre and exposure is additive to the
      effect of smoking. The diagnosis of chronic bronchitis is associated with a small
      but significant decrement in lung function.

PMID- 9039234
TI  - Impact of management guidelines on the outcome of severe community acquired
      pneumonia.
AB  - BACKGROUND: Ten years ago we published a study of 50 adults with severe community
      acquired pneumonia admitted to our intensive care unit and subsequently
      introduced guidelines for the management of severe community acquired pneumonia
      which are largely in accordance with those of the British Thoracic Society. The
      results of a follow up study are now reported in order to assess their impact on
      the outcome of this disease. METHODS: Fifty seven cases of severe community
      acquired pneumonia admitted to our ICU between 1984 and 1993 were studied. Causal
      pathogens, clinical and laboratory features of severity, antibiotic therapy and
      mortality were studied and, where possible, compared with results from the
      previous study. RESULTS: Streptococcus pneumoniae, Legionella pneumophila and
      Staphylococcus aureus were the most frequent causes of severe community acquired
      pneumonia, as in the previous study. The intensity of microbial investigation has
      increased, particularly with regard to pneumococcal and Legionella antigen
      testing, the latter allowing earlier diagnosis of Legionella infection than
      previously. In spite of this, no pathogen was identified in 33% of cases compared
      with 18% previously. Indices of severity of illness were widely recognised, and a
      decrease in unplanned transfers to the ICU following "unexpected"
      cardiorespiratory arrest from 25% to 7% (p < 0.02) was found. Antibiotic therapy
      largely reflected guideline recommendations with 98% receiving a beta-lactam
      agent and 91% erythromycin. The overall mortality was 58% compared with 54%
      previously. CONCLUSIONS: Management guidelines for severe community acquired
      pneumonia have been widely adopted but without a reduction in mortality in our
      hospital. Factors other than early diagnosis, appropriate antibiotics, or prompt
      ICU transfer may influence the outcome in severe community acquired pneumonia.

PMID- 9039236
TI  - Occupational asthma due to chrome and nickel electroplating.
AB  - BACKGROUND: Exposure to chromium during electroplating is a recognised though
      poorly characterised cause of occupational asthma. The first series of such
      patients referred to a specialist occupational lung disease clinic is reported.
      METHODS: The diagnosis of occupational asthma was made from a history of asthma
      with rest day improvement and confirmed by specific bronchial provocation testing
      with potassium dichromate and nickel chloride. RESULTS: Seven workers had been
      exposed to chrome and nickel fumes from electroplating for eight months to six
      years before asthma developed. One subject, although exposed for 11 years without
      symptoms, developed asthma after a single severe exposure during a ventilation
      failure. This was the only subject who had never smoked. The diagnosis was
      confirmed by specific bronchial challenges. Two workers had isolated immediate
      reactions, one a late asthmatic reaction, and four a dual response following
      exposure to nebulised potassium dichromate at 1-10 mg/ml. Two of the four
      subjects were also challenged with nebulised nickel chloride at 0.1-10 mg/ml. Two
      showed isolated late asthmatic reactions, in one at 0.1 mg/ml, where nickel was
      probably the primary sensitising agent. Four workers carried out two hourly
      measurements of peak expiratory flow over days at and away from work. All were
      scored as having occupational asthma using OASYS-2. Breathing zone air monitoring
      was carried out in 60 workers from four decorative and two hard chrome plating
      shops from workers with similar jobs to those sensitised. No measurement exceeded
      the current occupational exposure standard for chromate or nickel, the mean
      levels of chromate exposure for jobs similar to those of the affected workers
      were 9-15 micrograms/m3. CONCLUSION: Chrome used in electroplating is a potential
      cause of occupational asthma. Sensitivity to chrome in electroplaters may occur
      in situations where exposure levels are likely to be within the current exposure
      standards. There may be cross reactivity with nickel. Inhalation challenge with
      nebulised potassium dichromate solution is helpful in making the specific
      diagnosis where doubt exists.

PMID- 9039237
TI  - Analysis of bronchoalveolar lavage fluid in patients with chronic hepatitis C
      before and after treatment with interferon alpha.
AB  - BACKGROUND: Previous studies have shown that patients with idiopathic pulmonary
      fibrosis (IPF) were more likely to be seropositive for hepatitis C virus (HCV)
      than normal controls, and that patients with chronic hepatitis C treated with
      interferon alpha (IFN-alpha) sometimes developed pulmonary fibrosis. The
      possibility that HCV infection and/or treatment with IFN-alpha are involved in
      the pathogenesis of pulmonary fibrosis or alveolitis was investigated. METHODS: A
      prospective non-randomised study was performed in 13 healthy controls and in
      patients with chronic hepatitis C before (n = 13) and after (n = 10) treatment
      with IFN-alpha. Bronchoalveolar lavage (BAL) fluid cell counts, ratios and T cell
      subsets, and the concentrations of interleukin (IL)-1 beta, tumour necrosis
      factor(TNF)-alpha, and hepatocyte growth factor (HGF) were measured. RESULTS:
      Lymphocyte counts in the BAL fluid were significantly increased in both groups of
      patients (median (range) values: before treatment, 36.8 (1.5-226.0); after
      treatment, 16.2 (4.5-97.6)) compared with the normal controls (3.3 (0.5-32.3)).
      In the pretreatment group the activated T cell (HLA-Dr positive) count was also
      increased (51 (40-74)) compared with that in the normal controls (27 (4-52)), but
      after treatment it was decreased (40 (0-76)) compared with the pretreatment
      count. Administration of IFN-alpha did not affect these parameters. IL-1 beta,
      TNF-alpha, and HGF were not detected. CONCLUSIONS: These findings suggest that
      HCV infection is associated with increased counts of lymphocytes and neutrophils
      in BAL fluid and that treatment with IFN-alpha appears to alter lymphocyte
      surface markers.

PMID- 9039238
TI  - British Thoracic Society study of cryptogenic fibrosing alveolitis: current
      presentation and initial management. Fibrosing Alveolitis Subcommittee of the
      Research Committee of the British Thoracic Society.
AB  - BACKGROUND: Mortality due to cryptogenic fibrosing alveolitis (CFA) is
      increasing, particularly in the elderly. Optimum management remains uncertain and
      previous studies of the disease have largely been from specialist centres. A
      national study was carried out of the presentation and initial management of CFA
      in the UK. METHODS: All respiratory physicians in England, Scotland and Wales
      were invited to enter patients with newly diagnosed CFA over a two year period.
      CFA was diagnosed on histological grounds or according to clinical criteria which
      included the absence of a defined connective tissue disorder or pneumoconiosis.
      Participating physicians (n = 150) completed a questionnaire at patient entry and
      at all subsequent follow up visits and death. RESULTS: A total of 588 patients
      (373 men, 63%) were studied of whom 441 (75%) were referrals from primary care.
      Their mean (SD) age was 67.4 (10.0) years and median duration of symptoms at
      presentation was 9.0 months. Clubbing was more common in men (203/373; 54%) than
      in women (86/ 215; 40%); 209 patients (36%) were graded as severely breathless at
      presentation. A history of dust exposure (organic or inorganic) was present in
      274 patients (47%) of whom 87 had had some exposure to asbestos. Subjects exposed
      to dust were more likely to have smoked and had slightly higher mean lung
      volumes, but were otherwise indistinguishable from those not exposed in terms of
      clinical presentation, management, and outcome. Transbronchial biopsy specimens
      were taken in 164 patients (28%) and open lung biopsy specimens in 73 (12%), but
      60% had no histological diagnostic procedure. Biopsy procedures were more likely
      to be performed in younger patients, those with better lung function, and those
      with a history of asbestos exposure. At presentation a decision not to initiate
      specific treatment was made in 284 cases (48%). The decision to initiate
      treatment was made predominantly on symptomatic grounds. Two years after the
      close of entry to the study 266 patients (45%) had died. CONCLUSIONS: CFA is
      predominantly a disease of elderly patients and has a poor prognosis. Physicians
      generally considered CFA to be a clinical diagnosis and did not initiate
      treatment in up to half of patients at presentation.

PMID- 9039239
TI  - Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor
      antagonist, on bronchodilation in asthmatic subjects treated with and without
      inhaled corticosteroids.
AB  - BACKGROUND: Cysteinyl leukotriene release in association with airway inflammation
      is a feature of clinical asthma. The acute effects of montelukast (MK-0476), a
      potent, orally administered, specific cysteinyl leukotriene receptor antagonist,
      on airways obstruction was assessed in patients with mild to moderately severe
      asthma. METHODS: Twenty two asthmatic subjects were randomised to receive
      montelukast, 100 mg or 250 mg, or placebo in a double blind, three period,
      crossover trial. Ten of the patients were using concomitant inhaled
      corticosteroids. RESULTS: Montelukast increased the forced expiratory volume in
      one second (FEV1) from predose baseline values compared with placebo, the
      percentage point differences between montelukast and placebo being 8.6% (95% CI
      3.6 to 13.6) and 8.5% (95% CI 3.5 to 13.5) for the 100 mg and 250 mg doses,
      respectively. CONCLUSION: Single oral doses of montelukast 100 mg and 250 mg
      produced significant increases in FEV1 irrespective of the concurrent use of
      inhaled corticosteroids in asthmatic subjects with airflow limitation.

PMID- 9039240
TI  - Mortality of adults with asthma: a prospective cohort study.
AB  - BACKGROUND: Few studies have been published on the overall survival of adult
      patients with asthma. A cohort study was performed to assess the mortality from
      all causes, from chronic obstructive pulmonary disease, and from lung cancer
      among adult asthmatic subjects. METHODS: A population of 31,110 Finnish adult
      women and men, mostly twins, was studied to compare the 16 year mortality rates
      among asthmatic (n = 471) and non-asthmatic persons. A further 293 twin pairs,
      discordant for asthma, were also studied to determine whether the mortality of
      patients with asthma differs from that of their age matched siblings. RESULTS:
      Mortality from all causes was increased among asthmatic adults (age adjusted
      hazard ratios 1.49, 95% CI 1.09 to 2.05 for men and 1.53, 95% CI 1.10 to 2.13 for
      women), and mortality due to chronic obstructive pulmonary diseases was also
      significantly increased in asthmatic subjects. The risk of death due to lung
      cancer was increased in men with asthma (hazard ratio adjusted for smoking 3.19,
      95% CI 1.39 to 7.31). The risk ratios found among twins discordant for asthma
      corresponded to those found in the whole cohort. CONCLUSIONS: Survival in adults
      with asthma is worse than in those without asthma. The excess deaths due to
      chronic obstructive pulmonary disease may explain some part of the increased
      mortality rates, but not all of it.

PMID- 9039242
TI  - Vasopressin and oxytocin release during prolonged environmental hypoxia in the
      rat.
AB  - BACKGROUND: The mechanism causing peripheral oedema in hypoxaemic chronic
      obstructive pulmonary disease has not been established. Vasopressin, a powerful
      antidiuretic hormone involved in salt and water homeostasis, is released in
      response to acute hypoxia. However, the effect of prolonged hypoxaemia on
      hypothalamic and pituitary release of the magnocellular hypothalamic hormones,
      vasopressin and oxytocin, has not previously been studied. METHODS: Male Wistar
      rats were randomly allocated to either normobaric, hypoxic (10% O2) or control
      (21% O2) environmental chambers. An initial series of experiments examined plasma
      vasopressin concentration, osmolality, sodium concentration, packed cell volume
      (PCV), and weight gain at weekly intervals (n = 4-6) for six weeks. The maximum
      increase in plasma vasopressin concentration and PCV occurred after five weeks.
      In a second experiment vasopressin and oxytocin concentrations in the
      hypothalamus, pituitary gland, and plasma were measured in eight control and
      eight hypoxic rats after five weeks in the environmental chambers. RESULTS: In
      rats exposed to environmental hypoxia PCV increased (p < 0.001) and weight gain
      decreased (p < 0.05) compared with controls. The plasma vasopressin concentration
      increased progressively from a baseline of 1.36 (0.2) pmol/l (n = 6) to a maximum
      of 4.38 (0.8) pmol/l (n = 6; p < 0.01) during the first five weeks of
      environmental hypoxia (difference 3.02 (95% CI 1.18 to 4.86)). Plasma osmolality
      and sodium concentration were unchanged in hypoxic rats compared with controls
      during the six week period. The hypothalamic vasopressin concentration was
      increased (p < 0.001) after five weeks of environmental hypoxia (91.6 (4.8) pmol/
      hypothalamus) compared with controls (57.4 (5.1) pmol/hypothalamus), the
      difference being 34.2 pmol/hypothalamus (95% CI 21.6 to 46.5). The pituitary
      vasopressin concentration was unchanged. In hypoxic rats hypothalamic oxytocin
      (59.6 (3.2) pmol/hypothalamus) was greater (p < 0.01) than in controls (42 (3.8)
      pmol/hypothalamus), a difference of 17.6 pmol/ hypothalamus (95% CI 8.7 to 26.5).
      Similarly, the plasma oxytocin concentration was increased (p < 0.05) in hypoxic
      rats (6.78 (1.2) pmol/l) compared with controls (3.3 (0.8) pmol/l), a difference
      of 3.48 pmol/l (95% CI 0.89 to 6.07). The pituitary oxytocin concentration was
      unchanged in the two groups. CONCLUSIONS: These results demonstrate an increase
      in hypothalamic production of vasopressin and oxytocin in rats during prolonged
      hypoxaemia. Increased plasma concentrations of neurohypophysial hormones would be
      expected to impair sodium and water homeostasis in patients with hypoxaemia.
      However, the absence of change in the plasma osmolality and sodium concentrations
      in this study and previous clinical investigations suggests that compensatory
      mechanisms modulate the actions of both vasopressin and oxytocin. A reduction in
      renal blood flow or decreased renal responsiveness to the neurohypophyseal
      hormones may be involved.

PMID- 9039241
TI  - Release of prostaglandin E2 and leukotriene B4 by alveolar macrophages from
      patients with sarcoidosis.
AB  - BACKGROUND: Mediators released by alveolar macrophages, as well as by T cells,
      play an important part in modulating local immune processes in sarcoidosis. Among
      alveolar macrophage secretory products, arachidonic acid metabolites are known to
      regulate inflammatory and immune reactions. It has been suggested that cyclo
      oxygenase and lipoxygenase pathway metabolites of arachidonic acid modulate the
      evolution of the granulomatous inflammatory response in the lung differently.
      METHODS: Alveolar macrophages recovered from the bronchoalveolar lavage (BAL)
      fluid of 32 patients with sarcoidosis in different states of disease activity and
      10 normal subjects were evaluated for their ability to release prostaglandin E2
      (PGE2) and leukotriene B4 (LTB4). Alveolar macrophages were cultured in the
      presence or absence of opsonised zymosan (500 micrograms/ml), and PGE2 and LTB4
      levels in the culture supernatants were determined by enzyme immunoassay (EIA).
      RESULTS: Stimulated alveolar macrophages from patients with active sarcoidosis
      released higher LTB4 levels than those from normal subjects, but no differences
      in PGE2 release were observed between the two groups. The time course of LTB4
      release by activated alveolar macrophages showed that normal cells produced
      similar levels of the hydroxyacid during the early and late times of culture
      while LTB4 release by activated cells from patients with sarcoidosis increased
      markedly after 60 minutes of culture, remaining elevated until 24 hours.
      Indomethacin (3 x 10(6) M) caused the expected inhibition of PGE2 formation
      without affecting LTB4 release. CONCLUSIONS: These results suggest that alveolar
      macrophages from the BAL fluid of patients with active sarcoidosis are primed to
      release LTB4, which may contribute to the locally heightened immune response.

PMID- 9039243
TI  - Secondary failure of nasal intermittent positive pressure ventilation using the
      Monnal D: effects of changing ventilator.
AB  - BACKGROUND: Some patients started on nasal intermittent positive pressure
      ventilation (NIPPV) with the Monnal D ventilator deteriorate after a period. The
      effects of changing them to the Nippy ventilator were investigated. METHODS: The
      records of such patients were examined retrospectively. Comparisons were made
      between blood gas tensions and overnight oximetry records before NIPPV, 12 weeks
      after the initiation of NIPPV with the Monnal D, at the time of deterioration,
      and 12 weeks after initiation of treatment with the Nippy ventilator. RESULTS:
      Ten patients (seven women) were identified. Prior to starting NIPPV their mean
      (SD) age was 59.6 (8.39) years and their mean arterial oxygen and carbon dioxide
      tensions (PaO2 and PaCO2) while breathing air were 6.1 (1.79) and 9.6 (3.28) kPa,
      respectively. All were started on NIPPV with the Monnal D with improvements in
      symptoms, PaO2, PaCO2, and overnight oximetry after 12 weeks of treatment. After
      a mean interval of 118 (69.0) weeks all measures of ventilation had deteriorated
      and the patients were converted to the Nippy ventilator. Twelve weeks after
      initiation of treatment with the Nippy ventilator symptoms and overnight oximetry
      were improved again and the mean PaO2 and PaCO2 were 8.9 (1.27) and 6.9 (0.45)
      kPa, respectively. After a total mean period of 59 (26.9) weeks on the Nippy all
      but one of the patients have maintained this improvement. CONCLUSIONS: Support
      with NIPPV using the Monnal D ventilator may fail after an interval and changing
      to the Nippy ventilator can reverse this deterioration, probably because of its
      superior responsiveness to leaks and patient effort. The regular follow up of
      patients on long term NIPPV is necessary if secondary treatment failure is to be
      identified and effectively treated.

PMID- 9039245
TI  - Case of adults with cystic fibrosis has become an increasingly prominent part of
      the professional life of many respiratory physicians.

PMID- 9039244
TI  - Diffuse lung disease: product of genetic susceptibility and environmental
      encounters.
AB  - Diffuse (interstitial) lung disease comprises a wide variety of conditions,
      individually relatively uncommon but collectively being found in approximately 50
      per 100,000 population. Some of these diseases are of known aetiology but others
      are not. It has been suggested that the environment is a major contributory
      factor in this group of diseases. However, since not all individuals exposed to a
      common environment develop interstitial diseases, it can be hypothesised that
      there is a genetic predisposition to their development. These diseases cause
      major morbidity and mortality due to lung injury and fibrosis. It follows that,
      if individuals who are genetically predisposed to develop diseases characterised
      by lung injury and fibrosis can be identified, then management strategies can be
      designed which will attempt to identify and treat early disease and, in the
      longer term, to develop targeted genetic interventional approaches to treatment.

PMID- 9039246
TI  - Adrenal suppression with chronic dosing of fluticasone propionate compared with
      budesonide in adult asthmatic patients.
AB  - BACKGROUND: In a previous single dosing comparison between fluticasone propionate
      and budesonide differences in cortisol levels measured at 08.00 hours were
      observed at doses in excess of 1000 micrograms. The aim of this study was to
      compare the adrenal suppression caused by chronic twice daily dosing with inhaled
      fluticasone propionate (FP) and budesonide (B) given on a microgram equivalent
      basis by metered dose inhaler to asthmatic patients. METHODS: Twelve stable
      asthmatic patients of mean age 29.7 years with forced expiratory volume in one
      second (FEV1) 89.0% predicted and mid forced expiratory flow (FEF25-75) 58.9%
      predicted, on 400 micrograms/day or less of inhaled corticosteroid, were studied
      in a double blind, placebo controlled, crossover design comparing inhaled
      budesonide and fluticasone propionate in doses of 250 micrograms, 500 micrograms,
      and 1000 micrograms twice daily. Each dose was given at 08.00 hours and 22.00
      hours for four days by metered dose inhaler with mouth rinsing. Measurements were
      made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00
      hours, 10 hours after the eighth dose. RESULTS: The plasma cortisol levels (nmol/
      l) at 08.00 hours showed that fluticasone propionate produced lower cortisol
      levels than budesonide at all three dose levels: F500 333.8, B500 415.2 (95% CI
      28.9 to 134.0); F1000 308.3, B1000 380.3 (95% CI 10.5 to 133.5); F2000 207.3,
      B2000 318.5 (95% CI 5.8 to 216.7); placebo 399.9. Fluticasone produced greater
      effects than budesonide on the overnight urinary cortisol/creatinine ratio
      (nmol/mmol) at all three dose levels: F500 3.12, B500 5.55 (95% CI 0.16 to 3.79);
      F1000 2.54, B1000 6.12 (95% CI 1.25 to 5.91); F2000 2.07, B2000 6.09 (95% CI 0.88
      to 7.18); placebo 5.23. CONCLUSIONS: With repeated dosing across a dose range of
      250-1000 micrograms twice daily, fluticasone propionate produced significantly
      greater adrenal suppression than budesonide for both plasma and urinary cortisol.
      It was therefore possible to demonstrate differences between fluticasone and
      budesonide at lower doses with chronic dosing from those previously found with
      single dosing when given on a microgram equivalent basis in asthmatic patients.
      Factors contributing to the systemic adverse activity profile of fluticasone
      comprise enhanced receptor potency, prolonged receptor residency time, greater
      tissue retention, and a longer elimination half life.

PMID- 9039249
TI  - Cystic fibrosis diagnosed by molecular genetic investigation in the mother of a
      patient with cystic fibrosis.

PMID- 9039248
TI  - Quality of life and hospital re-admission in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: There is some evidence that quality of life (QOL) in patients with
      chronic obstructive pulmonary disease (COPD) may predict clinical outcomes and
      use of resources. This study examined whether QOL scores could prospectively
      predict re-admission for COPD or death within 12 months of an original admission,
      and whether QOL scores predicted home nebuliser provision. METHODS: The study was
      carried out in all acute medical wards of Aberdeen Royal Infirmary, Woodend and
      City Hospitals, Aberdeen over 12 months. A total of 377 patients admitted with an
      exacerbation of COPD were identified in this time, 111 of whom were not included
      in the study because they refused the interview or died before discharge. The
      remaining 266 patients completed the St George's Respiratory Questionnaire
      (SGRQ). Information on spirometric parameters, nebuliser provision at discharge,
      provision of domiciliary oxygen, and re-admission within 12 months was collected
      from patient notes. RESULTS: The mean age of the patients was 68 years and 53%
      were men. The mean (SD) forced expiratory volume in one second (FEV1) was 38.8
      (18.0)% predicted and forced vital capacity (FVC) was 58.9 (23.8)% predicted.
      Higher (worse) scores on the SGRQ were significantly related to re-admission for
      COPD in the next 12 months (difference = 4.8, 95% CI 1.6 to 8.0). Patients who
      were re-admitted and died from COPD did not differ in SGRQ scores from those who
      were re-admitted and survived for more than 12 months. Re-admission was not
      related to sex, age, or pulmonary function. One hundred and thirty eight patients
      did not have a home nebuliser before admission. Of these, 14 were provided with a
      home nebuliser at discharge. Patients provided with nebulisers had significantly
      worse SGRQ scores and worse FVC. The 41 patients given domiciliary oxygen did not
      differ in SGRQ or spirometric parameters. Logistic regression analysis of the
      three SGRQ subscales (Symptom, Impact and Activity), adjusting for lung function,
      age and sex, showed that all three subscales were significantly related to
      hospital readmission and that Impact scores were related to nebuliser provision.
      Women did not differ from men in Symptom scores on the SGRQ but differed markedly
      on the Activity and Impact scales. CONCLUSIONS: It is concluded that poor scores
      on the SGRQ, a QOL scale which measures patient distress and coping, are
      associated with re-admission for COPD and use of resources such as nebulisers,
      independent of physiological measures of disease severity.

PMID- 9039247
TI  - Effect of inhaled frusemide and oral indomethacin on the airway response to
      hypertonic saline challenge in asthmatic subjects.
AB  - BACKGROUND: Inhaled frusemide inhibits airway narrowing and causes a transient
      increase in forced expiratory volume in one second (FEV1) during hypertonic
      saline challenge. This inhibitory effect could be secondary to prostaglandin
      release during challenge. The involvement of prostaglandins in the inhibitory
      action of frusemide during challenge with 4.5% NaCl was investigated by
      premedicating with indomethacin, a prostaglandin synthetase inhibitor. METHODS:
      Fourteen asthmatic subjects (eight women) aged 26.6 (range 18-56) years
      participated in a double blind, placebo controlled, crossover study. The subjects
      attended five times and inhaled 4.5% NaCl for 0.5, 0.75, 1, 1.5, 2, 4, 8, 8, and
      8 minutes, or part thereof, or until a provocative dose causing a 20% fall in
      FEV1 (PD20 FEV1) was recorded. Indomethacin (100 mg/day) or placebo were taken
      three days before all visits, except control day. The FEV1 was measured and
      frusemide (38.0 (6.4) mg, pH = 9) or vehicle (0.9% NaCl, pH = 9) were inhaled 10
      minutes before the challenge. Bronchodilation was calculated as the percentage
      rise in FEV1 from the prechallenge FEV1 to the highest FEV1 recorded during the
      challenge. RESULTS: Frusemide caused a fold increase in PD20 FEV1 compared with
      the vehicle which was similar in the presence of both indomethacin and placebo
      (3.7 (95% CI 2.0 to 7.3) versus 3.3 (2.0 to 5.4)). Frusemide, but not vehicle,
      also caused a transient percentage rise in FEV1 during challenge with 4.5% NaCl
      which was not blocked by indomethacin (3.6% (1.2 to 6.0)) or placebo (3.1% (1.0
      to 5.2)). CONCLUSIONS: Inhaled frusemide inhibited airway narrowing and caused a
      transient increase in FEV1 during challenge with 4.5% NaCl. These effects were
      not blocked by indomethacin, which suggests that the inhibitory action of
      frusemide is not secondary to prostaglandin release.

PMID- 9039250
TI  - Thromboembolism related to a Port-a-Cath device in a patient with cystic
      fibrosis.
AB  - The case is described of a potentially life threatening complication relating to
      the use of a totally implantable venous access device (Port-a-Cath) in a 28 year
      old patient with cystic fibrosis. The device was inserted in 1990 and used
      repeatedly for antibiotic therapy without any complications. In 1995, during
      assessment for double lung transplantation, a 3 cm thrombus was found at the tip
      of the catheter in the right atrium. Embolisation of the thrombus to the
      pulmonary arteries occurred after the infusion of recombinant tissue plasminogen
      activator (rt-PA). Thrombus formation may be associated with totally implantable
      venous access devices and thromboembolism may occur following the use of
      thrombolytic agents in the treatment of such thrombosis.

PMID- 9039252
TI  - BTS sarcoidosis study.

PMID- 9039251
TI  - Transverse myelitis: a reversible complication of bronchial artery embolisation
      in cystic fibrosis.
AB  - The case history is presented of a young woman with cystic fibrosis and life
      threatening haemoptysis. Angiography revealed enlarged bronchial vessels, one of
      which supplied the contralateral lung. Transverse myelitis developed following
      bronchial artery embolisation but recovery was rapid and nearly complete.
      Haemoptysis did not recur during four years of follow up.

PMID- 9039253
TI  - BTS sarcoidosis study.

PMID- 9039254
TI  - Automatic nasal continuous positive airway pressure titration in the laboratory:
      patient outcomes.
AB  - BACKGROUND: Manual titration of nasal continuous positive airway pressure (NCPAP)
      treatment for obstructive sleep apnoea (OSA) is time consuming and expensive.
      There are now "intelligent" NCPAP machines that try to find the ideal pressure
      for a patient by monitoring a combination of apnoeas, hypopnoeas, inspiratory
      flow limitation, and snoring. Although these machines usually find similar
      pressures to skilled technicians, it is not clear if their use in the sleep
      laboratory influences subsequent acceptance by patients. This study addresses
      this question. METHODS: One hundred and twenty two patients undergoing a trial of
      NCPAP were randomly allocated to either manual or automatic (Horizon, DeVilbiss)
      titration of pressure during their first night on NCPAP in a hospital sleep
      laboratory. The primary outcome (available on 112 patients) was the acceptance of
      NCPAP or otherwise six weeks following the initial titration night. Baseline
      indicators of severity were compared between the groups, as were the pressures
      selected and the subsequent improvement in the sleepiness of the patients.
      RESULTS: The initial severity of OSA was not significantly different in the two
      groups and the mean (SD) NCPAP pressures were similar (manual 8.7 (2.5) cm H2O,
      automatic 8.2 (2.1) cm H2O). The percentage of patients successfully established
      on CPAP at six weeks was 64% and 73% for the manual and automatic groups,
      respectively; 13% and 2%, respectively, in the manual and automatic groups had
      given up completely (p < 0.05), and there were about equal numbers (23% versus
      25%) in the two groups who were still undecided. CONCLUSIONS: The substitution of
      automatic NCPAP titration for manual titration during the first night of NCPAP in
      patients with OSA does not reduce the number accepting the treatment at six weeks
      and may slightly improve it. This has important cost saving potential.

PMID- 9039255
TI  - Regulatory mechanisms in stem cell biology.

PMID- 9039256
TI  - Genetic control of cell division patterns in developing plants.

PMID- 9039257
TI  - Connecting cell behavior to patterning: lessons from the cell cycle.

PMID- 9039258
TI  - When checkpoints fail.

PMID- 9039259
TI  - p53, the cellular gatekeeper for growth and division.

PMID- 9039260
TI  - Oncoprotein networks.

PMID- 9039261
TI  - Programmed cell death in animal development.

PMID- 9039262
TI  - Apoptosis by death factor.

PMID- 9039263
TI  - Human chromosomal fragile site FRA16B is an amplified AT-rich minisatellite
      repeat.
AB  - Fragile sites are nonstaining gaps in chromosomes induced by specific tissue
      culture conditions. They vary both in population frequency and in the culture
      conditions required for induction. Folate-sensitive fragile sites are due to
      expansion of p(CCG)n trinucleotide repeats; however, the relationship between
      sequence composition and the chemistry of induction of fragile sites is unclear.
      To clarify this relationship, the distamycin A-sensitive fragile site FRA16B was
      isolated by positional cloning and found to be an expanded 33 bp AT-rich
      minisatellite repeat, p(ATATA TTATATATTATATCTAATAATATATC/ATA)n (consistent with
      DNA sequence binding preferences of chemicals that induce its cytogenetic
      expression). Therefore the mutation mechanism associated with trinucleotide
      repeats is also a property of minisatellite repeats (variable number tandem
      repeats).

PMID- 9039264
TI  - Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a
      widely conserved protein family.
AB  - Meiotic recombination in S. cerevisiae is initiated by double-strand breaks
      (DSBs). In certain mutants, breaks accumulate with a covalently attached protein,
      suggesting that cleavage is catalyzed by the DSB-associated protein via a
      topoisomerase-like transesterase mechanism. We have purified these protein-DNA
      complexes and identified the protein as Spo11, one of several proteins required
      for DSB formation. These findings strongly implicate Spo11 as the catalytic
      subunit of the meiotic DNA cleavage activity. This is the first identification of
      a biochemical function for any of the gene products involved in DSB formation.
      Spo11 defines a protein family with other members in fission yeast, nematodes,
      and archaebacteria. The S. pombe homolog, rec12p, is also known to be required
      for meiotic recombination. Thus, these findings provide direct evidence that the
      mechanism of meiotic recombination initiation is evolutionarily conserved.

PMID- 9039265
TI  - Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia
      and seizures in the lethargic (lh) mouse.
AB  - Ca2+ channel beta subunits regulate voltage-dependent calcium currents through
      direct interaction with alpha 1 subunits. The beta- and alpha 1-binding motifs
      are conserved, and all beta subunits can stimulate current amplitude, voltage
      dependence, and kinetics when coexpressed with various alpha 1 subunits. We used
      a positional candidate approach to determine that the ataxia and seizures in the
      lethargic (lh) mouse arise from mutation of the beta-subunit gene Cchb4 on mouse
      chromosome 2. A four-nucleotide insertion into a splice donor site results in
      exon skipping, translational frameshift, and protein truncation with loss of the
      alpha 1-binding site. The lethargic phenotype is the first example of a mammalian
      neurological disease caused by an inherited defect in a non-pore-forming subunit
      of a voltage-gated ion channel.

PMID- 9039266
TI  - MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural
      organization, dilated cardiomyopathy, and heart failure.
AB  - MLP is a LIM-only protein of terminally differentiated striated muscle cells,
      where it accumulates at actin-based structures involved in cytoarchitecture
      organization. To assess its role in muscle differentiation, we disrupted the MLP
      gene in mice. MLP (-/-) mice developed dilated cardiomyopathy with hypertrophy
      and heart failure after birth. Ultrastructural analysis revealed dramatic
      disruption of cardiomyocyte cytoarchitecture. At birth, these hearts were not
      hypertrophic, but already abnormally soft, with cell-autonomous and MLP-sensitive
      alterations in cytoarchitecture. Thus, MLP promotes proper cardiomyocyte
      cytoarchitecture, whose perturbation can lead to dilated cardiomyopathy. In vivo
      analysis revealed that MLP-deficient mice reproduce the morphological and
      clinical picture of dilated cardiomyopathy and heart failure in humans, providing
      the first model for this condition in a genetically manipulatable organism.

PMID- 9039267
TI  - CDK-independent activation of estrogen receptor by cyclin D1.
AB  - Both cyclin D1 and estrogens have an essential role in regulating proliferation
      of breast epithelial cells. We show here a novel role for cyclin D1 in growth
      regulation of estrogen-responsive tissues by potentiating transcription of
      estrogen receptor-regulated genes. Cyclin D1 mediates this activation independent
      of complex formation to a CDK partner. Cyclin D1 activates estrogen receptor
      mediated transcription in the absence of estrogen and enhances transcription in
      its presence. The activation of estrogen receptor by cyclin D1 is not inhibited
      by anti-estrogens. A direct physical binding of cyclin D1 to the hormone binding
      domain of the estrogen receptor results in an increased binding of the receptor
      to estrogen response element sequences, and upregulates estrogen receptor
      mediated transcription. These results highlight a novel role for cyclin D1 as a
      CDK-independent activator of the estrogen receptor.

PMID- 9039269
TI  - Climate change and malaria transmission.
AB  - There is a consensus among climatologists that our planet is experiencing a
      progressive rise in surface temperature due to the increased production of
      "greenhouse" gases. Some of the possible consequences of elevated temperature on
      malaria transmission are examined in the present review. A simple mathematical
      model is first used to examine the effect of temperature on the ability of
      Anopheles maculipennis to transmit vivax malaria. This indicates that small
      increases in temperature at low temperatures may increase the risk of
      transmission substantially. This is important, since vulnerable communities,
      poorly protected by health services, in areas of unstable or no malaria are
      likely to be at increased risk of future outbreaks. In contrast, areas of stable
      transmission may be little affected by rising temperature. It is thought that
      global warming will lead to coastal flooding, changes in precipitation and,
      indirectly, changes in land use. Just how these changes will effect transmission
      at a regional level requires an understanding of the ecology of local vectors,
      since environmental changes which favour malaria transmission in one vector
      species may reduce it in another. Methods for predicting future changes in
      malaria in different regions are discussed, highlighting the need for further
      research in this area. Most importantly, there is a need for researchers to
      validate the accuracy of the models used for predicting malaria and to confirm
      the assumptions on which the models are based.

PMID- 9039268
TI  - Secretory leukocyte protease inhibitor: a macrophage product induced by and
      antagonistic to bacterial lipopolysaccharide.
AB  - To explore regulation of potentially lethal responses to bacterial
      lipopolysaccharide (LPS), we used differential display under LPS-free conditions
      to compare macrophage cell lines from two strains of mice congenic for a locus
      affecting LPS sensitivity. LPS-hyporesponsive cells, primary macrophages, and
      polymorphonuclear leukocytes transcribed secretory leukocyte protease inhibitor
      (SLPI), a known epithelial cell-derived inhibitor of leukocyte serine proteases.
      Transfection of macrophages with SLPI suppressed LPS-induced activation of NF
      kappa B and production of nitric oxide and TNF alpha. The ability of interferon
      gamma (IFN gamma) to restore LPS responsiveness is a hallmark of the LPS
      hyporesponsive phenotype. IFN gamma suppressed expression of SLPI and restored
      LPS responsiveness to SLPI-producing cells. Thus, SLPI is an LPS-induced IFN
      gamma-suppressible phagocyte product that serves to inhibit LPS responses.

PMID- 9039271
TI  - Antimalarial activity in crude extracts of Malawian medicinal plants.
AB  - Aqueous and organic fractions from Cassia abbreviata, Senna petersiana (both
      Caesalpiniaceae) and Azanza garckeana (Malvaceae) were tested for in-vitro
      antimalarial activity against the multi-drug-resistant, Vietnam-Smith strain of
      Plasmodium falciparum; VI/S. Both roots and leaves from these Malawian medicinal
      plants were investigated. High activity, with a median inhibitory concentration <
      3 micrograms/ml, was seen in the organic fractions of C. abbreviata and S.
      petersiana, the two species most commonly cited by traditional healers in an
      ethnobotanical investigation of Malawian antimalarials. Extracts of A. garckeana
      showed weaker activity. Biologically active compounds have thus been detected
      within species of the family Caesalpiniaceae. Ethnobotanical investigation
      appears to be useful in identifying plants with antimalarial activity.

PMID- 9039270
TI  - The effect of oral iron therapy during treatment for Plasmodium falciparum
      malaria with sulphadoxine-pyrimethamine on Malawian children under 5 years of
      age.
AB  - In sub-Saharan countries, although malaria and malaria-associated anaemia are
      major public health problems, the usefulness of supplementary iron treatment for
      children with malaria-associated anaemia is unknown. In a 6-week period during
      the 1995 rainy season, 222 Malawian children aged < 5 years, who sought treatment
      for malaria, had > or = 500 parasites/microliter blood and at least 5 g
      haemoglobin (HB)/dl blood and whose parents gave consent, were randomized into a
      prospective study comparing the efficacy of sulphadoxine- pyrimethamine only
      (SP), SP plus daily iron (SPD) and SP plus weekly iron (SPW) as treatment for
      malaria-associated anaemia. The patients had their HB concentrations measured on
      enrollment (day 0), just before antimalarial treatment, and on days 3, 7, 14, 21
      and 28; 215 (96.8%) completed the 28-day study. Among the children with 5-8 g
      HB/dl on enrolment, HB gain by the end of the study was significantly greater
      than in the children with > 8 g HB/dl initially (4.1 v. 2.2 g/dl; P < 0.05), and
      those in the SPD group gained significantly more HB by days 21 and 28 (3.6 and
      4.9 g/dl, respectively) than those in either the SPW (2.7 and 3.7 g/dl,
      respectively) or the S2 groups (2.6 and 3.5 g/dl, respectively); there was no
      difference in HB gain between the SP and SPW groups. Type of treatment had no
      apparent effect, at any time during the study, on HB gains in those patients who
      had > 8 g HB/dl on enrolment. Thus the children with 5-8 g HB/dl on enrolment
      benefited from daily iron therapy whereas those with > 8 g HB/dl derived no
      significant benefit; improvement in HB depended most on whether enrolment HB was
      < or = 8.0 g/dl. As treatment with an effective antimalarial drug resulted in HB
      gains, irrespective of treatment group or HB concentration at enrolment, the
      anaemia observed may be mostly related to malaria. However, as a larger
      proportion of the iron-treated patients failed to clear their parasitaemias than
      of those given SP alone, oral iron may inhibit SP action. It is therefore
      recommended that, for children with both malaria and malaria-associated anaemia,
      the malaria should first be cleared with an effective antimalarial drug, such as
      SP, before the anaemia, if it still persists, is treated with iron.

PMID- 9039273
TI  - Schistosoma mansoni: effect of aestivation on the intra-molluscan stages and the
      survival rate of infected Biomphalaria pfeifferi.
AB  - Following exposure to the miracidia of Schistosoma mansoni, Biomphalaria
      pfeifferi were induced to aestivate immediately ('0 h') or on days 7, 14 or 21
      post-infection and then re-activated at various times. The proportions of snails
      found to be alive at weekly intervals after re-activation were found to be
      related to the length of time the snails had spent between infection and
      aestivation (I-A), varying from 100% (0 h) to 5% (21 days). The mean numbers of
      cercariae produced by the snails after re-activation also varied with I-A, being
      highest in those that aestivated immediately post-infection, and cercarial
      development was delayed by prolonged desiccation of the infected snails, the
      intra-molluscan development of S. mansoni is affected by the aestivation of the
      snail host.

PMID- 9039272
TI  - Efficacy of 101 antimicrobials and other agents on the development of
      Cryptosporidium parvum in vitro.
AB  - An in-situ ELISA was used as a primary screen to test the effects of 101
      antimicrobials and other agents on the development of Cryptosporidium parvum in
      vitro. Over 40 of the compounds displayed some form of anticryptosporidial
      activity, and dose-response curves were generated for 40 of these. The in-situ
      ELISA makes a highly effective primary, pharmaceutical screen for C parvum, to be
      used prior to more detailed microscopical, toxicological or in-vivo assays.

PMID- 9039274
TI  - A survey of larval and adult mosquitoes on the flood plains of Bangladesh, in
      relation to flood-control activities.
AB  - A mosquito survey was carried out between October 1991 and November 1992 on the
      flood plains of Bangladesh, as part of a baseline study designed to help predict
      the effects on vector-borne diseases of embanking rivers under the Bangladesh
      Government's Flood Action Plan. Overall, 15 species of larval and 15 species of
      adult anophelines were collected, along with 13 larval and 21 adult culicines.
      Anophelines made up only 6% of the mosquitoes caught at human bait. The most
      abundant anopheline biting man was Anopheles vagus, the dominant species in all
      nine sampling villages. The other recognized malaria vectors in the flood plains
      of Bangladesh, namely An. philippinensis, An. aconitus and An. annularis, were
      collected but in relatively low numbers. Culex vishnui was the most abundant
      biting culicine in all villages. Biting mosquitoes showed a bimodal seasonality
      of biting, with peaks between February and April and September and October. All
      biting mosquitoes showed a significant preference for outdoor biting. The
      densities of the mosquito populations are more likely to be affected by the large
      scale environmental changes which have occurred in Bangladesh, as well as the
      dramatic increase in the density of the human population, than by the river
      embankments per se.

PMID- 9039276
TI  - A simple protocol for the indirect xenodiagnosis of Leishmania infantum in the
      blood of HIV-infected patients.

PMID- 9039275
TI  - Glomerulonephritis and nephrotic syndrome in Plasmodium chabaudi chabaudi: a
      potential murine model of chronic P. malariae infection.

PMID- 9039277
TI  - No evidence for increased production of nitric oxide in C57BL/6J mice infected
      with Echinococcus multilocularis.

PMID- 9039278
TI  - Ivermectin treatment of mansonellosis in Blanchisseuse, Trinidad, West Indies.

PMID- 9039279
TI  - Adult Onchocerca volvulus from east and west Africa exhibit similar antigenicity
      with pooled sera from onchocerciasis patients.

PMID- 9039280
TI  - Serological survey of markers of infection with viral hepatitis among the Yukpa
      Amerindians from western Venezuela.

PMID- 9039281
TI  - Rotavirus infection in African, non-human primates.

PMID- 9039282
TI  - Symptomatic hypercalcaemia is rare in tuberculous patients in Hong Kong.

PMID- 9039283
TI  - The blood-feeding behaviour of Phlebotomus martini (Diptera:Psychodidae): is it a
      question of photoperiodism or circadian rhythm?

PMID- 9039284
TI  - The prevalence of a microbiota in the digestive tract of Phlebotomus papatasi.

PMID- 9039285
TI  - Stonefish sting: an occupational hazard in Hong Kong.

PMID- 9039286
TI  - Genetic studies of atopy and atopic dermatitis.
AB  - Atopy and the atopic disorders are likely to result from multifactorial
      inheritance, with interaction between genetic and environmental factors. It has
      been proposed that at least two major mechanisms, non-antigen specific (total IgE
      levels) and antigen specific (specific IgE antibodies and skin tests), regulate
      the immune response to allergens in humans: firstly, a gene/genes independent of
      the human leucocyte antigen system which is involved in the regulation of total
      IgE levels, and secondly, a specific immune response gene/genes associated with
      major histocompatibility complex class II genes which are involved in antigen
      specific mechanisms. Candidate genes have been proposed for both mechanisms and
      linkage has been found between atopy and at least three different gene loci. This
      paper reviews the evidence supporting a genetic basis for atopy and atopic
      dermatitis and outlines recent advances in the molecular genetic mapping of genes
      associated with these disorders.

PMID- 9039287
TI  - Morphological and biochemical analyses on fibroblasts and self-produced collagens
      in a novel three-dimensional culture.
AB  - The addition of L-ascorbic acid 2-phosphate (Asc 2-P), which is active and stable
      under a conventional culture condition, could render dermal fibroblasts to the
      organization of a dermis-like structure on a plastic dish without any prior
      treatment. The cell layer was composed of multilayered fibroblasts surrounded by
      dense extracellular matrices. Confocal microscopic examination disclosed that the
      fibroblasts in the upper layer were spindle-shaped and those in the lower layer
      were polygonal. Electron microscopic examination revealed the accumulation of
      mature collagen fibrils in the intercellular space. These morphological
      observations suggest that the cell layer may resemble the dermis-like structure.
      Biochemical analyses revealed that the hydroxyproline content of the cell layer
      increased in a time-dependent manner, while the monolayer culture system without.
      Asc 2-P yielded no measurable amount of hydroxyproline. On sodium dodecylsulphate
      polyacrylamide gel electrophoresis, neutral insoluble collagens extracted from
      the cell layer showed the identical electrophoretic pattern to those from the
      human dermis. In addition, these bands were completely digested by bacterial
      collagenase. This novel culture system could provide a simple tool with which to
      investigate the collagen metabolism by fibroblasts under more physiological
      conditions.

PMID- 9039288
TI  - Fluorescence spectroscopy: a rapid, noninvasive method for measurement of skin
      surface thickness of topical agents.
AB  - We report the quantification of skin surface thickness of topical agents by in
      vivo fluorescence spectroscopy, and demonstrate its potential uses for assessment
      of application technique and substantivity. A series of studies were performed on
      forearm skin of eight normal subjects using three creams which have intrinsic
      fluorescence: a sunscreen (Neutrogena SPF15 waterproof cream), an antiseptic
      (Hewlett's cream) and a steroid (Trimovate (clobetasone butyrate) cream).
      Initially, the dose-response relationship was established for each agent by
      applying a series of five doses (0.5-8 microliters/cm2) and measuring cream
      fluorescence using appropriate excitation and emission wavelengths. Next, the
      influence of application technique was examined by comparing light application of
      cream with firm rubbing. Substantivity of the three creams was assessed on dry
      skin by taking fluorescence measurements over 8 h. Finally, water resistance of 2
      microliters/cm2 of sunscreen and antiseptic cream were compared by measuring
      fluorescence after each of four water immersions. The fluorescence intensity was
      strongly correlated with the logarithm of surface density. r = 1.0, 0.92 and 0.98
      for sunscreen, antiseptic and steroid creams, respectively, allowing derivation
      of a simple expression for equivalent thickness. Surface thickness of each cream
      was lower following firm rubbing compared with light application (P < 0.01). The
      rate constants for reduction of surface density of the three creams with time on
      dry skin were not significantly different. However, on washed skin, the rate
      constant was higher for Hewlett's than Neutrogena cream (0.503 and 0.243 h.
      respectively, P = 0.02), with a higher rate for each cream on wet compared with
      dry skin (P < 0.001). Hence, fluorescence spectroscopy is a simple, rapid method
      for measurement of cream thickness in vivo. The many potential applications in
      dermatology include quantitative assessment of application technique and
      substantivity of topical agents.

PMID- 9039289
TI  - Constitutive endothelial and inducible nitric oxide synthase in inflammatory
      dermatoses.
AB  - We have used immunohistochemistry to localize the expression of the constitutive
      endothelial and inducible forms of the enzyme nitric oxide synthase (NOS) in skin
      from involved and uninvolved sites in patients with atopic dermatitis (AD) and
      allergic contact dermatitis (CD). Endothelial NOS (eNOS) immunoreactivity was
      localized to vascular endothelium in the dermis of both involved and uninvolved
      skin from all patients. Inducible NOS (iNOS) immunoreactivity was found to be
      closely associated with the upper dermal microvasculature in all the involved AD
      biopsies, but only in two of 10 uninvolved AD biopsies. CD biopsies were taken
      from 10 positive skin patch test sites and iNOS immunoreactivity was detected in
      all of these. iNOS immunoreactivity was detected in only one of the negative
      patch test biopsies. Both the extent and intensity of iNOS immunoreactivity was
      lower in CD than in AD skin lesions. The presence of eNOS in the skin is
      necessary for constitutive NO-mediated dilatation of the dermal vasculature.
      Induction of iNOS in the dermal endothelium and in perivascular inflammatory
      cells may be significant with respect to the roles of NO in both the vasodilatory
      component of the inflammatory response and in the modulation of immune responses
      in the skin.

PMID- 9039290
TI  - Chronic mucocutaneous candidosis associated with hypothyroidism: a distinct
      syndrome?
AB  - Chronic mucocutaneous candidosis (CMC) is a rare, complex disorder characterized
      by chronic and recurrent candida infections of the skin, nails and oropharynx. In
      over 50% of cases there is an associated endocrine disease, the complex being
      described as the candida endocrinopathy syndrome. Inheritance of familial
      endocrine associated cases has been thought to follow an autosomal recessive
      pattern. In addition, autosomal recessive and autosomal dominant forms of CMC not
      associated with endocrinopathy have been described. We report a new syndrome in
      which there is vertical transmission of CMC within families associated with
      primary hypothyroidism. This suggests that the candida endocrinopathy syndrome
      can be subdivided into at least two types, one associated with hypoparathyroidism
      and/or hypoadrenalism which is inherited as an autosomal recessive trait, the
      other associated with hypothyroidism which is an autosomal dominant disease. We
      emphasize the importance of early and regular monitoring thyroid function in
      individuals with CMC and a need to provide appropriate genetic counselling to
      affected members.

PMID- 9039291
TI  - Metallothionein expression in basaloid proliferations overlying dermatofibromas
      and in basal cell carcinomas.
AB  - Basaloid proliferations overlying dermatofibromas which morphologically resemble
      superficial basal cell carcinomas have been interpreted as both
      reactive/regressive and frankly malignant. Metallothioneins (MTs) are low
      molecular-weight proteins with a selective binding affinity for heavy metal ions.
      MTs has been proposed to represent a biological marker of carcinogenesis and, in
      a variety of human tumours, a correlation between immunohistochemically
      overexpression of MT and aggressive clinical behaviour has been shown. In order
      to clarify the nature of basaloid proliferations overlying dermatofibromas, we
      examined, immunohistochemically, 10 dermatofibromas with overlying simple
      hyperplasia, 16 dermatofibromas with overlying basaloid proliferation, and 35
      basal cell carcinomas, for expression of MT. In normal epidermis, the basal
      keratinocytes showed cytoplasmatic MT immunoreactivity. The staining intensity
      was stronger in the basal cells of the rete ridges, an observation which is in
      accordance with the high proportion of S-phase cells in this area. Simple
      hyperplasia showed the same MT expression pattern as normal epidermis. Basaloid
      proliferations stained like superficial and nodular basal cell carcinomas. Of
      nodular basal cell carcinomas, 92% (12 of 13) showed decreased/absent MT
      immunoreactivity, while 86% (six of seven) of infiltrating/morphoea-like basal
      cell carcinomas showed overexpression of MT (P = 0.001, Fisher's exact test). The
      results demonstrate that MT overexpression in basal cell carcinomas is correlated
      with infiltrative growth pattern. The similar expression of MT in basaloid
      proliferations and 'non-infiltrating' basal cell carcinomas suggests that these
      lesions share a common change in metabolism and/or differentiation.

PMID- 9039293
TI  - The use of perichondrial cutaneous grafts to repair defects of the lower third of
      the nose.
AB  - The reconstruction of surgical defects on the nasal tip and nasal ala which
      require both skin coverage and underlying support is often a complex surgical
      problem. The perichondrial cutaneous graft (PCCG) is a composite graft of skin
      and perichondrium harvested from the conchal bowl of the car. It is an excellent
      alternative to full-thickness skin grafts and local flaps for reconstructing
      defects of the lower third of the nose. This composite graft, which is composed
      of epidermis, dermis, a small amount of subcutaneous tissue, and the underlying
      perichondrium, yields excellent cosmetic and functional results in a simple,
      single-stage, out-patient procedure. This article describes and illustrates the
      repair of surgical defects on the nasal tip and nasal ala using the PCCG.

PMID- 9039292
TI  - Altered expression of the hemidesmosome-anchoring filament complex proteins in
      basal cell carcinoma: possible role in the origin of peritumoral lacunae.
AB  - Basal cell carcinoma (BCC) is a frequent skin cancer with low metastatic
      potential. Expression of the anchoring filament proteins, native laminin-5 and
      its individual alpha 3, beta 3 and gamma 2 chains, uncein. and linear IgA antigen
      was examined by immunostaining in 17 BCC with different histological subtypes.
      Immunoreactivity of the hemidesmosomal proteins, integrin alpha 6 beta 4, 230-kDa
      bullous pemphigoid antigen (BP-230 Ag) and plectin/HD-1, and that of dermal
      epidermal junction (DEJ) components, integrin alpha 2 beta 1, laminin-1, collagen
      IV, and collagen VII was also analysed. Around tumour nests, the labelling of
      laminin-5 was absent or markedly reduced in 12 BCC (comprising eight solid BCC,
      three adenoid BCC and one keratotic BCC) and strong in five BCC (comprising three
      adenoid BCC, one keratotic BCC and one adenoid and keratotic BCC). Intriguingly,
      in tumour cells of 12 BCC including laminin-5 negative tumours, a cytoplasmic
      reactivity of the laminin gamma 2 chain was detected, but not that of the alpha 3
      and beta 3 chains. In the basement membrane of the epidermis overlying tumour
      nests, the labelling of laminin-5 was always strong. Uncein, linear IgA disease
      antigen, and integrin alpha 6 beta 4 were absent in solid BCC and weakly
      expressed in adenoid or keratotic BCC. For plectin/HD-1 and BP-230 Ag, a
      cytoplasmic reactivity was detected in the majority of the tumour cells. The
      labelling of integrin alpha 2 beta 1, laminin-1, collagen IV and collagen VII
      indicated no alteration in the synthesis of these proteins. In peritumoral
      lacunae, immunoreactivity of hemidesmosome and anchoring filament proteins was
      absent, except for plectin/HD-1 on the tumour side and sometimes for laminin-5 on
      the stromal side, while laminin-1, collagen IV and collagen VII were detected on
      the stromal side. These findings suggest that the components of the hemidesmosome
      anchoring filament complex are not synthetized or assembled properly in BCC, and
      that the alteration of these adhesion structures may be the cause of peritumoral
      lacunae.

PMID- 9039295
TI  - Modulation by Chinese herbal therapy of immune mechanisms in the skin of patients
      with atopic eczema.
AB  - Ten patients with atopic eczema (AE) received treatment with Chinese herbal
      therapy (CHT; Zemaphyte) for 2 months. The severity of the eczema was recorded
      and skin biopsies were taken from lesional (L) and non-lesional (NL) skin before
      and after treatment. The skin biopsies were stained to detect T-cell subsets
      (CD4, CD8, CD45Ro and CD25), macrophage subsets (RFD7), dendritic cells (RFD1).
      Langerhans cells (CD1), HLA-DR, low-affinity IgE receptors (CD23) and high
      affinity IgE receptors (15A5, 22H7). A quantitative assessment of the numbers of
      positively stained cells was made. Monoclonal antibody binding specifically to
      CD23(Fc epsilon RII) was used, in combination with cell subset monoclonal
      antibodies to quantify the cellular distribution of CD23 antigen in the skin.
      Following 2 months of treatment with CHT, erythema was reduced by 53%. There was
      also a significant reduction in HLA-DR expression. The numbers of RFD1 + CD23 +,
      RFD7 + CD23 +, CD1 + CD23+ and CD25 + cells in lesional skin decreased
      significantly after treatment (RFD1 + CD23 + from 0.39 to 0.21, RFD7 + CD23 +
      from 0.29 to 0.16. CD1 + CD23 + from 0.24 to 0.09, CD25 + from 0.84 to 0.31 in
      epidermis and from 1.62 to 0.94 in dermis (mean cells numbers per unit area). No
      significant change in cell numbers in NL skin or expression of Fc epsilon RI in
      either L or NL samples was observed after treatment. This study confirms that CHT
      is clinically efficacious and that clinical improvement is associated with a
      significant reduction in antigen-presenting cells expressing CD23.

PMID- 9039294
TI  - Increased levels of type I and III collagen and hyaluronan in scleroderma skin.
AB  - The aminoterminal propeptide of type III procollagen (PIIINP) and the
      carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were
      measured in plasma and suction blister fluid from 13 systemic sclerosis patients
      and 11 healthy volunteers. Suction blisters and skin biopsies were from the
      transition zone between normal skin and scleroderma, and uninvolved abdominal
      skin of patients. The median value of suction blister PIIINP from the transition
      zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was
      localized to the dermis by immunohistochemical techniques. PICP and HA levels in
      blisters from the transition zone were 87% and 53%, respectively, above the
      levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from
      the transition zone were 67% and 63%, respectively, higher than the levels
      measured in healthy volunteers. In plasma from scleroderma patients levels of
      PIIINP and HA were 38% and 127% higher, respectively, than in plasma of healthy
      volunteers. The plasma PICP level was not significantly higher in scleroderma
      patients. Finally, PICP, PIIINP and HA levels were several times higher in
      suction blister fluid than in plasma. The data indicate that a fibrogenetic
      process takes place in the transition zone of scleroderma. The method may be used
      to monitor the progression of scleroderma skin lesions in vivo.

PMID- 9039296
TI  - Bacillary angiomatosis: presentation of six patients, some with unusual features.
AB  - Bacillary angiomatosis (BA) is an unusual systemic vascular proliferation seen
      predominantly in patients with the acquired immunodeficiency syndrome. These
      vascular lesions are probably due to infection with a Bartonella species, most
      often B. henselae and, in some patients, B. quintana. BA is treatable and often
      curable, but without therapy, may be life-threatening. Clinically, the lesions,
      when superficial, are said to often resemble pyogenic granulomas, appearing
      polypoid histologically with an epidermal collarette. We now report six patients,
      three of whom showed lesions of BA morphologically and histologically distinct
      from the other patients reported to date. Two patients lesions appeared
      clinically as violaceous plaques and tumours resembling Kaposi's sarcoma; one of
      them had lesions histologically reminiscent of a papular angiokeratoma; and the
      other had lesions histologically suggestive of a combination of Kaposi's sarcoma
      and BA. Another patient presented with soft subcutaneous nodules which
      histologically showed extensive acute inflammation characteristic of an acute
      abscess, but which also displayed proliferating dilated small blood vessels with
      bulbous endothelial cells adjacent to numerous bacteria and also containing them.
      The Grocott-methenamine silver stain and the Warthin-Starry stain showed the
      organisms to better advantage in lesions of all six patients, although bacteria
      were also evident with the haematoxylin and eosin, periodic acid-Schiff and
      alcian blue stains.

PMID- 9039297
TI  - Post-adolescent acne: a review of clinical features.
AB  - Acne is usually recognized as a disorder of adolescence. However, the referral of
      patients over the age of 25 years with acne has significantly increased over the
      past 10 years. The clinical features of 200 patients over the age of 25 years,
      referred to our department for treatment of acne, were evaluated with a view to
      establishing possible aetiological factors. There were 152 (76%) women and 48
      (24%) men. The mean age of the patients was 35.5 years (range 25-55 years). The
      acne was mild or moderate in severity, consisting principally of inflammatory
      lesions, with mean total acne grade (Leeds Grading Scale) of 1.125 for men and
      0.75 for women. Most patients had persistent acne; but true late-onset acne
      (onset after the age of 25 years) was seen in 28 (18.4%) of women and four (8.3%)
      of men. Thirty-seven per cent of women had features of hyperandrogenicity. One
      hundred and sixty-four patients (82%) had failed to respond to multiple courses
      of antibiotics, and 64 (32%) had relapsed after treatment with one or more
      courses of isotretinoin. External factors, such as cosmetics, drugs and
      occupation, were not found to be significant aetiological factors. A family
      history revealed that 100 (50%) of patients had a first-degree relative with post
      adolescent acne. Patients with post-adolescent acne appear to represent an
      increasingly important population of acne sufferers. External factors do not seem
      to have a significant aetiological role. Two main clinical groups were
      identified: those with persistent acne and those with late-onset acne. A minority
      of women also had features of hyperandrogenicity. These patients, and those with
      late-onset acne, may represent a subgroup who have underlying abnormalities of
      ovarian, adrenal or local androgen metabolism, and require separate
      investigation.

PMID- 9039298
TI  - Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole.
AB  - Liarozole, a novel imidazole derivative, inhibits the cytochrome P450-dependent 4
      hydroxylation of retinoic acid, resulting in increased tissue levels of retinoic
      acid. Twelve male patients with ichthyosis were given oral liarozole, 150 mg
      twice daily, in an open study for 12 weeks. Immunohistochemical parameters of
      inflammation, epidermal proliferation and differentiation were assessed before
      and after treatment. Extent and severity of the skin lesions was markedly reduced
      in all patients. Clinical side-effects were reminiscent of those with synthetic
      retinoids. No relevant changes were found in the haematological, urinary and
      biochemical parameters. Immunohistochemical assessment showed a statistically
      significant induction of keratin 4 after liarozole treatment in 10 of 12
      patients. In two of these patients keratin 13 was induced. This open study showed
      that oral liarozole treatment was efficacious and well tolerated in the treatment
      of different types of ichthyosis. The immunohistochemical results suggest a
      retinoid mechanism as the mode of action.

PMID- 9039299
TI  - Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.
AB  - A prospective, open, multicentre study was performed to investigate the efficacy
      and safety of long-term treatment with cyclosporin in adults with severe atopic
      dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8
      weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then
      adjusted according to response. Disease activity was monitored using the six
      area, six-sign score and the proportion of skin involved. Pruritus and sleep
      disturbance were assessed using four-point scales. Response was further evaluated
      on a five-point scale. Adverse events, blood pressure and serum biochemistry were
      monitored. Tolerability was assessed on a five-point scale. One hundred subjects
      were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to
      remission (three), inadequate response (seven), protocol violations (11) and
      adverse events (14, of which seven were probably treatment related). Cyclosporin
      produced rapid and highly significant improvements in all indices of disease
      activity. Sixty-five subjects considered that they had shown a considerable
      improvement or complete clearance of disease. Most patients relapsed after
      cessation of treatment, but neither signs nor symptoms had returned to baseline
      severity 8 weeks later. Blood pressure and serum creatinine levels increased
      slightly, and in one subject renal impairment was a major factor contributing to
      withdrawal of the drug. Overall, 85 subjects rated the tolerability of
      cyclosporin as good or very good. The results indicate that cyclosporin has a
      place in the long-term treatment of severe atopic dermatitis provided that
      appropriate patients are selected and careful monitoring is performed.

PMID- 9039300
TI  - Comparison of cyclosporin A pharmacokinetics of a new microemulsion formulation
      and standard oral preparation in patients with psoriasis.
AB  - Cyclosporin A (CyA) is a potent immunosuppressive drug which has shown efficacy
      in various skin disorders. The bioavailability of the oral CyA formulation
      (Sandimmun) is approximately 30%, showing high interpatient and intrapatient
      variability. The steady-state pharmacokinetics, efficacy and tolerability of CyA
      in two formulations: commercial Sandimmun soft gelatin capsules (CyA-SGC) and a
      newer oral formulation (Sandimmun Neoral: CyA-NOF), were compared in an open
      prospective study with a crossover between the two treatments in 19 patients with
      psoriasis. Each patient received a twice-daily treatment of CyA with a clinically
      effective dose of 2-5 mg/kg per day. The individual dosages were kept unchanged
      for at least 2 weeks before study entry and over the 42-day course of the study.
      At entry, patients were switched to CyA-NOF for 4 weeks and then back to CyA-SGC
      for another 2 weeks. Pharmacokinetic profiles were assessed at steady-state on
      day 14 while the patients were on CyA-NOF, and on day 42 while on CyA-SGC.
      Switching from CyA-SGC to CyA-NOF using 1:1 dose conversion resulted in an
      increased absorption of the drug. On average there was a 61% increase in maximum
      drug concentration (Cmax) and a 32% increase in the area under the steady-state
      blood concentration-time curve (AUC): Cmin was comparable in the two
      formulations. The increases in Cmax and AUC were associated with some increase in
      the clinical efficacy of the treatment. The number of adverse events reported by
      the patients and observed by the investigators were increased during CyA-NOF; the
      mean serum creatinine levels were not affected. An increased and a more
      consistent and predictable absorption of CyA is achieved with the new oral
      microemulsion formulation.

PMID- 9039302
TI  - Nailfold capillary abnormalities in patients with Sjogren's syndrome and systemic
      lupus erythematosus.
AB  - It is unknown whether primary Sjogren's syndrome (pSS) and systemic lupus
      erythematosus (SLE) have the same nailfold capillary abnormality, although they
      show similarity in several clinical, immunological and genetic aspects.
      Microscopy of the nailfold capillaries was undertaken in the two diseases and the
      observed parameters were compared with age- and sex-matched controls using
      analysis of variance. pSS and SLE showed a different frequency in their clinical
      and laboratory findings, except for the presence of anti-SS-A/B antibodies. All
      nailfold capillary parameters showed significantly higher values than those of
      corresponding normal controls, although between pSS and SLE there was no
      significant difference. The results may indicate that pSS and SLE are part of a
      spectrum of disorder.

PMID- 9039301
TI  - Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate
      cream in the treatment of chronic plaque psoriasis. A randomized, double-blind,
      parallel group multicentre study. Calcipotriol Study Group.
AB  - The efficacy, safety and tolerability of calcipotriol cream was compared with
      betamethasone 17-valerate cream in the treatment of plaque-type psoriasis in a
      multicentre double-blind, parallel group study. Patients with stable mild-to
      moderate chronic disease were randomized to treatment with either calcipotriol,
      50 micrograms/g, in a cream formulation (210 patients) or betamethasone 17
      valerate cream, 1 mg/g (211 patients). After a wash-out period of 2 weeks, the
      treatment was applied twice daily, without occlusion, for 8 weeks or to complete
      clearing. The severity of psoriasis was assessed using the PASI at baseline and
      after 4 and 8 weeks treatment. The mean percentage reduction of PASI from
      baseline to end of treatment was 47.8% in the calcipotriol group and 45.4% in the
      betamethasone group. The reduction from baseline was highly significant in both
      groups, but the difference between the groups was not significant. There was a
      difference in the reduction in thickness of the lesions in favour of
      calcipotriol. The investigator's as well as the patient's overall assessment of
      treatment response at end of treatment showed no difference between the two
      treatment groups. Treatment-related adverse events were more frequent with
      calcipotriol than betamethasone. Lesional/perilesional irritation was reported in
      16% and 9% (P = 0.03), and facial irritation in 10% and 0.5% (P < 0.001),
      respectively. No change was found in serum levels of calcium. Calcipotriol in a
      cream formulation was effective, safe, well-tolerated, and equal in effect to
      betamethasone valerate cream.

PMID- 9039303
TI  - In psoriasis the epidermis, including the subepidermal vascular plexus, grows
      downwards into the dermis.
AB  - In psoriatic lesions, capillaries in the papillary bodies seem elongated and
      increased in number. Most researchers postulate that there is angiogenesis of
      intrapapillary capillaries in psoriatic plaques. In this study we will show, by
      means of computer-aided three-dimensional reconstructions in four patients
      suffering from chronic plaque-type psoriasis, and in a healthy volunteer, that
      the elongation and increase of intrapapillary capillaries are not the result of
      angiogenesis. Our three-dimensional reconstructions show that the papillary body
      of psoriasis contains lymph capillaries besides the blood capillaries.
      Additionally, an inclusion of two tips of papillary bodies into one papilla at
      the base of the rete ridges becomes obvious. The vessels of the two tips are
      connected by a horizontal vessel. At the level of the horizontal connecting
      vessel there is the blind beginning of a lymphatic vessel. The connecting blood
      vessel, as well as the lymph capillary, belong to the horizontal subpapillary
      venous plexus but lie within the papillary body. The three-dimensional
      reconstructions show that by growing towards the dermis, the rete ridges include
      the vessels of the horizontal plexus. Surrounded by rete ridges, these vessels
      appear as intrapapillary capillaries.

PMID- 9039304
TI  - Progressive fetal axillary cystic lymphangioma with coexistent naevus flammeus.
AB  - We report the rare occurrence of a progressive fetal axillary cystic lymphangioma
      coexistent with an overlying naevus flammeus. The fetus at 22 weeks' gestation
      was found to have a 37 x 35 mm left axillary multiloculated mass without colour
      flow imaging. Amniocentesis showed a normal 46,XX karyotype. Multiple fine-needle
      aspirations of the mass in the second and third trimesters obtained blood-stained
      chocolate-coloured fluid containing numerous erythrocytes and lymphocytes but
      proved ineffective in lessening the progressive growth of the mass. The mother
      underwent caesarean delivery and a healthy neonate was born with a 141 x 81 mm
      left axillary cystic lymphangioma and a 50 x 35 mm coexistent naevus flammeus.
      The neonate was well after simple excision of the lesions. Although cystic
      lymphangiomas arising in the axilla enlarge progressively during fetal life, our
      case suggests a good prognosis and except for genetic evaluation, no prenatal
      intervention is required.

PMID- 9039305
TI  - Solar urticaria in an infant.
AB  - A 2-year-old girl presented with a history of an erythematous rash which occurred
      immediately after exposure to sunlight and had been a problem since birth.
      Extensive laboratory investigations to exclude genophotodermatoses,
      photosensitivity secondary to metabolic disorders and photoaggravated dermatoses
      were negative. Monochromator irradiation phototesting demonstrated immediate
      erythematous flares to all ultraviolet B (UVB), UVA and visible wavelengths up to
      500 nm. A diagnosis of solar urticaria was made and she responded to loratidine
      10 mg daily. We believe this is the first report of solar urticaria, confirmed by
      phototesting with a monochromator so early in life.

PMID- 9039306
TI  - Urticaria haemorrhagica profunda.
AB  - Substantial subcutaneous haemorrhage without preceding trauma or underlying
      bleeding disorder is a rare occurrence in dermatological practice, essentially
      restricted to early childhood (acute haemorrhagic oedema of childhood). We report
      an adolescent with a morphologically unique bleeding manifestation. A 16-year-old
      boy presented with two episodes of massive subcutaneous haemorrhage in
      association with urticarial vasculitis. There was no history of preceding trauma
      or haemorrhagic disorder. Haemorrhage was observed in areas typically affected by
      angioedema, such as the periorbital, perioral, lingual, sublingual and laryngeal
      areas. History revealed an atopic diathesis with hay fever and examination showed
      alopecia areata. An antinuclear antibody titre and the presence of lupus
      anticoagulant indicated transient antiphospholipid antibodies. As urticaria
      corresponds to urticaria profunda angioedema, we hypothesize a pathophysiological
      relationship between superficial urticarial vasculitis and the deep variant of
      urticarial vasculitic disease, leading to the unique morphology present in our
      patient.

PMID- 9039307
TI  - Lupus erythematosus profundus associated with neonatal lupus erythematosus.
AB  - A female infant with neonatal lupus erythematosus had scanty discoid lesions and
      concurrent lupus erythematosus profundus on the face. Depression of lupus
      erythematosus profundus lesions was still evident at 4 years of age.

PMID- 9039308
TI  - Childhood paraneoplastic pemphigus associated with Castleman's tumour.
AB  - Paraneoplastic pemphigus (PNP) is a rare condition virtually always seen in
      adults. We report a 13-year-old boy who developed PNP associated with Castleman's
      tumour. His condition mimicked Stevens-Johnson syndrome and responded to tumour
      resection and immunosuppressive therapy.

PMID- 9039309
TI  - Diffuse hypertrichosis during treatment with 5% topical minoxidil.
AB  - Five women affected by androgenetic alopecia developed severe hypertrichosis of
      the face and limbs after 2-3 months of treatment with 5% topical minoxidil.
      Minoxidil was discontinued and in all patients the hypertrichosis disappeared
      from the face and arms after 1-3 months, and from legs after 4-5 months. Systemic
      absorption of minoxidil, and a high sensitivity to minoxidil of the follicular
      apparatus in these areas, is hypothesized.

PMID- 9039310
TI  - Infection with Mycobacterium avium-intracellulare with abscess, ulceration and
      fistula formation.
AB  - Infections caused by Mycobacterium avium-intracellulare complex are generally
      manifested as pulmonary disease, osteomyelitis or lymphadenitis, and cutaneous
      infection is rare. We describe a case of M. intracellulare infection of the skin
      in a 79-year-old man without apparent immunologically disabling disease or
      therapy. He had cutaneous infection of the right hand over 10 years, developing a
      fistula and, finally, an ulcer and abscess, 2 months before his death from heart
      failure. Mycobacterium intracellulare was identified by both microbiological
      characteristics and DNA-DNA hybridization.

PMID- 9039311
TI  - Aggressive B-cell lymphoma induced by Epstein-Barr virus infection in
      erythrodermic cutaneous T-cell lymphoma.
AB  - The coexistence of two cutaneous non-Hodgkin's lymphomas of different lineage is
      rare. We report a patient with an indolent erythrodermic cutaneous T-cell
      lymphoma followed by an aggressive B-cell lymphoma. To our best knowledge, this
      is the first report describing Epstein-Barr virus-associated B-cell lymphoma in a
      patient with cutaneous T-cell lymphoma. We suggest that the long-standing
      cutaneous T-cell lymphoma, as well as the long-term chemotherapy, suppressed host
      immunity and caused reactivation of latent Epstein-Barr virus.

PMID- 9039312
TI  - Symptomatic porphyria secondary to hepatocellular carcinoma.
AB  - A 58-year-old woman gave a 6-month history of porphyria-like photosensitivity.
      Fractioned porphyrin analysis by high performance liquid chromatography revealed
      elevated concentrations of all urinary porphyrins and faecal protoporphyrin.
      Hepatocellular carcinoma had developed in an otherwise normal liver. Tumour
      tissue fluoresced strongly under fluorescence microscopy, exhibiting elevated
      activity of three haem-biosynthetic enzymes, delta-aminolevulinic acid (ALA)
      synthase. ALA dehydratase and porphobilinogen deaminase. This patient did not
      satisfy any of the criteria for inherited porphyria. The patient's symptoms were
      relieved after excision of the liver tumour. This strongly suggests that
      excessive porphyrin synthesis originated from the tumour tissue. Primary
      porphyria-like photosensitivity occurs as a paraneoplastic phenomenon, secondary
      to hepatocellular carcinoma.

PMID- 9039313
TI  - Hyperplastic pseudofolliculitis barbae associated with cyclosporin.

PMID- 9039314
TI  - Thiopurine methyltransferase levels should be measured before commencing patients
      on azathioprine.

PMID- 9039315
TI  - Treatment of inflammatory linear verrucous epidermal naevus with topical vitamin
      D3.

PMID- 9039316
TI  - Soluble vascular cell adhesion molecule-1 (VCAM-1) in the serum of patients with
      atopic dermatitis.

PMID- 9039317
TI  - Increased expression of inducible nitric oxide (NO) synthase.

PMID- 9039318
TI  - Malignant melanoma in childhood.

PMID- 9039319
TI  - Malassezia yeast density in HIV-positive individuals.

PMID- 9039320
TI  - Tinea capitis in south-east London: an outbreak of Trichophyton tonsurans
      infection.

PMID- 9039321
TI  - Onychomycosis and linear nail growth.

PMID- 9039322
TI  - Dyspareunia and vulvodynia are probably common manifestations of factitious
      urticaria.

PMID- 9039323
TI  - Eosinophil major basic protein in autologous serum and saline skin tests in
      chronic idiopathic urticaria.

PMID- 9039324
TI  - Neutrophilic panniculitis associated with myelodysplastic syndromes.

PMID- 9039325
TI  - Bizarre gyrate erythema associated with malignant thymoma.

PMID- 9039326
TI  - Pott's puffy tumour.

PMID- 9039327
TI  - Association between interleukin-1 receptor antagonist (IL-1ra) gene polymorphism
      and early and late-onset psoriasis.

PMID- 9039328
TI  - Flautist's chin.

PMID- 9039329
TI  - Mineralocorticoid receptors and glucocorticoid receptors.

PMID- 9039330
TI  - Clinical manifestations of genetic defects affecting gonadotrophins and their
      receptors.
AB  - Raised activity of the LH axis caused by activating mutations of LH receptor gene
      presents with precocious puberty in boys, analogous to the presentation of LH
      secreting pituitary adenomas (Faggiano et al., 1983; Ambrosi et al., 1990). LH
      "hyperactivity' in females appears to have no effect. Hyperactivity of the FSH
      axis caused by activating mutations of the FSH receptor gene might parallel the
      presentation of FSH secreting pituitary adenomas with Sertoli cell hypertrophy in
      men (Heseltine et al., 1989) or reversible premature ovarian failure in women
      (Moses et al., 1986; Okuda et al., 1989). Indeed the first such case to be
      described is a male who maintained testicular volume and fertility in the absence
      of gonadotrophins (Gromoll et al., 1996). Female precocious puberty may require
      hyperactivity of both gonadotrophin axes because of the "two-cell' arrangement
      required for ovarian oestrogen production. Mutations of the Gs alpha-subunit gene
      can mimic this situation in some women with the McCune-Albright syndrome
      (Malchoff et al., 1994). Lack of LH activity caused by defects in the LH beta
      molecule causes infertility in men and that resulting from inactivating mutations
      of the LH receptor gene causes Leydig cell agenesis in men while ovarian
      development in females is relatively normal. Lack of FSH activity caused by
      defects in the FSH beta caused infertility in a female, and that caused by
      inactivating mutations of the FSH receptor gene causes ovarian dysgenesis in
      women but only variable depression of spermatogenesis in men. Incidentally, this
      categorization of reproductive disorders may also be applied to the TSH axis.
      Pituitary adenomas and activating mutations of the TSH receptor gene (Parma et
      al., 1993) cause hyperthyroidism and TSH beta gene defects (Hayashizaki et al.,
      1989) and inactivating mutations of the TSH receptor gene (Sunthornthepvarakul et
      al., 1995) cause hypothyroidism. To complete the analogy with thyroid disorders,
      it is curious that despite structural similarities with the TSH receptor, neither
      LH nor FSH receptor autoantibodies have a prominent role in ovarian
      pathophysiology (Moncayo et al., 1989; Van Weissenbruch et al., 1991; Simoni et
      al., 1993). Complete gonadotrophin resistance is likely to be very rare, however,
      so what are we likely to find in partial gonadotrophin resistance? Might the
      "resistant ovary syndrome' come right in the end, with corresponding minor FSH
      receptor mutations? Experience with insulin and androgen resistance syndromes
      suggests that such a scenario is unlikely. Insulin receptor gene mutations are
      found in extreme Type A insulin resistance but not in moderate forms of insulin
      resistance (O'Rahilly et al., 1991). Androgen receptor gene mutations are found
      in nearly all cases of complete androgen insensitivity but rarely in partial
      forms (Patterson et al., 1994). Mild resistance to hormone action is rarely
      detectable in relatives who are heterozygous for receptor mutations which are
      inherited in a recessive pattern. It seems unlikely therefore, that individuals
      heterozygous for inactivating receptor mutations will manifest symptoms of
      reproductive disorders and account for common conditions. Thus, while mutation
      analysis provides new insights into the gender specific role of the
      gonadotrophins the cause of early gonadal failure in the majority of individuals
      remains a mystery.

PMID- 9039331
TI  - Growth hormone and the maintenance of adult bone mineral density.

PMID- 9039332
TI  - Calcium-sensing receptor mutations in familial hypocalciuric hypercalcaemia with
      recurrent pancreatitis.
AB  - OBJECTIVE: Pancreatitis is an unusual complication of the benign disorder
      familial hypocalciuric hypercalcaemia (FHH) such that it could represent a
      distinct subgroup of FHH. In order to study this, we investigated three FHH
      kindreds with recurrent pancreatitis for mutations of the extracellular calcium
      sensing receptor (CaR) to identify a possible common genetic aetiology for
      typical FHH and that associated with pancreatitis. PATIENTS AND METHODS: Three
      FHH kindreds (18 affected, 14 unaffected members) in which the proband had
      presented with recurrent pancreatitis were identified. The entire 3234bp coding
      region of the CaR gene was examined by direct DNA sequencing using fluorochrome
      labelled dideoxy-terminators. Mutations were confirmed and demonstrated to co
      segregate with FHH by restriction enzyme analysis. RESULTS: Three novel
      heterozygous missense mutations (Asn178Asp, Arg220Gln and Pro221Ser) in the
      extracellular domain of the CaR were identified in each of the probands. These
      mutations, which co-segregated with the hypercalcaemia, were not detected as
      common polymorphisms in 55 unrelated normocalcaemic controls. CONCLUSIONS:
      Familial hypocalciuric hypercalcaemia with recurrent pancreatitis is associated
      with calcium-sensing receptor mutations, and thus this variant has the same
      genetic aetiology as typical familial hypocalciuric hypercalcaemia.

PMID- 9039333
TI  - Growth hormone versus placebo treatment for one year in growth hormone deficient
      adults: increase in exercise capacity and normalization of body composition.
AB  - OBJECTIVE: Studies with GH substitution in GH-deficient (GHD) adults lasting more
      than 6 months have so far been uncontrolled. End-points such as physical fitness
      and body composition may be subject to a considerable placebo effect which
      weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day)
      versus placebo treatment for 12 months. DESIGN: Twenty-nine patients (mean age
      45.5 +/- 2.0 years) with adult-onset GHD were studied in a double-blind, parallel
      design. Measurements of body composition by means of conventional anthropometry,
      bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and
      isometric muscle strength were performed at baseline and after 12 months
      treatment. For body composition measurements a control group of 39 healthy, age
      and sex-matched subjects was included. RESULTS: Sum of skinfolds (SKF) at 4 sites
      decreased significantly after GH treatment. Total body fat (TBF) as assessed by
      DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by
      SKF revealed significantly higher levels compared to DEXA and BIA, although all
      estimates intercorrelated closely. Visceral and subcutaneous abdominal fat
      decreased by 25 and 17%, respectively after GH (P < 0.01) to levels no longer
      different from the control group. CT of the mid thigh revealed a significant
      reduction in fat tissue and a significant increase in muscle volume after GH
      treatment, both of which resulted in a normalization of the muscle: fat ratio (%)
      (placebo: 58:42 (baseline) vs 58:42 (12 months); GH: 66:34 (baseline) vs 72:28
      (12 months) (P = 0.002); normal subjects: 67:33 (P < 0.05 when compared to 12
      months placebo data)). Total body resistance and resistance relative to muscle
      volume decreased significantly after GH treatment suggesting over-hydration as
      compared to normal subjects. Exercise capacity (kJ) increased significantly after
      GH treatment (placebo: 54.7 +/- 9.8 (baseline) vs 51.6 +/- 8.2 (12 months); GH:
      64.9 +/- 13.3 (baseline) vs 73.5 +/- 13.6 (12 months) (P < 0.05)). Isometric
      quadriceps strength increased after GH but no treatment effect could be detected
      owing to a small increase in the placebo group. Serum IGF-I levels (microgram/l)
      were low baseline and increased markedly after GH treatment to a level exceeding
      that of normal subjects (270 +/- 31 (12 months GH) vs 156 +/- 8 (normal subjects
      (P < 0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The
      number of adverse effects were higher in the GH group after 3 months, but not
      after 6 and 12 months. CONCLUSIONS: (1) The reduction in excess visceral fat
      during GH substitution is pronounced and sustained; (2) beneficial effects on
      total body fat, muscle volume and physical fitness can be reproduced during
      prolonged placebo-controlled conditions; (3) uncontrolled data on muscle strength
      must be interpreted with caution; (4) a daily GH substitution dose of 2 IU/m2
      seems too high in many adult patients.

PMID- 9039334
TI  - Glucose tolerance, insulin secretion, insulin sensitivity and glucose
      effectiveness in normal and overweight hyperthyroid women.
AB  - OBJECTIVE: Inter-relationships between insulin sensitivity and body weight in
      patients with hyperthyroidism remain incompletely understood. We have examined
      whether a mild excess of body weight exacerbates the metabolic abnormalities of
      spontaneous hyperthyroidism. DESIGN AND PATIENTS: Insulin-modified intravenous
      glucose tolerance tests were performed on 14 hyperthyroid women with body mass
      indices (BMI) ranging from 21 to 31 kg/m2. A control group of 19 healthy women
      matched for age and BMI was also studied. MEASUREMENTS: Intravenous glucose
      tolerance (KG), first and second-phase integrated insulin responses to glucose,
      the integrated glucose area under the curve (AUC), and minimal model parameters
      of insulin sensitivity (SI) and glucose effectiveness (SG) were determined.
      RESULTS: Hyperthyroid women had mean KG, glucose-induced insulin secretion and SG
      values similar to those in control women. The mean glucose AUC was higher in
      hyperthyroid patients (P < 0.05). Lower insulin sensitivity was observed in
      hyperthyroid patients than in control women (SI = 0.38 +/- 0.07 vs 0.59 +/- 0.07
      l/min pmol 10(4) (mean +/- SEM), P < 0.05). A steeper decline in insulin
      sensitivity with increase in body mass index was found in hyperthyroid women when
      compared with the control group, after adjusting for age. When groups were
      compared according to their BMI, hyperthyroid women with normal weight (BMI < or
      = 25 kg/m2, n = 8) had mean KG, insulin response to glucose, glucose AUC, SG and
      SI values similar to those in normal weight control women (n = 11). Overweight
      hyperthyroid patients (BMI > 25 kg/m2, n = 6) had a higher (P < 0.05) second
      phase insulin response to glucose than normal weight patients, a higher glucose
      AUC (P < 0.05) than normal weight patients and overweight controls (n = 8), and a
      lower SI (P < 0.05) than normal weight patients and overweight controls. SG was
      not influenced by BMI in hyperthyroid patients. CONCLUSIONS: These results
      suggest that overall glucose tolerance was not significantly affected in normal
      weight hyperthyroid women. However, when a moderate excess of weight is also
      present, a state of clear insulin resistance occurs.

PMID- 9039335
TI  - Differential stimulation of cortisol and dehydroepiandrosterone levels by food in
      obese and normal subjects: relation to body fat distribution.
AB  - BACKGROUND: It has been previously shown that food intake elevates circulating
      ACTH and cortisol levels, but no report has been published regarding the changes
      in circulating dehydroepiandrosterone (DHEA). DHEA was originally described as a
      weak androgen, but more recently it has been associated with a wide range of
      metabolic functions. In addition, previous studies have described a hyper
      responsive hypothalamo-pituitary-adrenal axis in obese subjects in response to
      various stimuli, but the specific response to food has not been studied. SUBJECTS
      AND DESIGN: We studied the effect of food on the hypothalamo-pituitary-adrenal
      axis in 20 subjects of normal body mass index (BMI range 18-25) and also in a
      group of 12 obese subjects (BMI range 34-61). Levels of glucose, insulin, ACTH,
      cortisol and dehydroepiandrosterone were measured every 20 minutes. RESULTS: A
      small rise in DHEA accompanies the rise in circulating ACTH and cortisol in
      response to food in both lean and obese subjects, but DHEA rose independently of
      cortisol and ACTH on the fasting day. In the obese subjects, food induced a
      significantly greater change in serum cortisol (peak cortisol rise (mean +/-
      SEM); normal-weight group, 169 +/- 14%; obese group, 294 +/- 23%) and in the
      cortisol/DHEA ratio (area under the curve; normal-weight group, 202 +/- 15%;
      obese group, 292 +/- 29%) than in the normal-weight subjects. This difference was
      particularly notable in those with central-type obesity (waist/hip ratio > 0.80).
      A group of the normal, jean female subjects showed no cortisol rise after food
      intake. CONCLUSION: Our results suggest that DHEA may vary independently of
      circulating cortisol, and that the cortisol response to food is enhanced in obese
      subjects, particularly in those with central obesity. We speculate that there may
      be a caused connection between the cortisol response to food in normal subjects,
      and the subsequent distribution of fat if such subjects overeat sufficiently to
      become obese.

PMID- 9039336
TI  - Bone mineral density in relation to glucocorticoid substitution therapy in adult
      patients with 21-hydroxylase deficiency.
AB  - OBJECTIVE: There are only limited data on bone mineral density (BMD) in adult
      patients with 21-hydroxylase deficiency (21-OHD). We have defined the effects of
      different glucocorticoid substitution therapies on BMD and body composition in
      these patients. DESIGN: Cross-sectional. PATIENTS: Thirty-two adult patients with
      21-OHD. MEASUREMENTS: Patients were examined auxologically and biochemically. BMD
      was examined in the left femoral neck and lumbar vertebrae 2-4 (L2-4) with dual X
      ray absorptiometry. The results were compared with national reference data.
      RESULTS: Mean height was 170.1 cm (-1.36 standard deviation scores (SDS) for the
      men and 156.3 cm (-1.68 SDS) for the women. These were significantly less (P <
      0.001) than the mean national final heights. Mean BMD Z-score ((raw score -
      population reference mean)/SD) was -0.52 in L2-4 and -0.83 in the left femoral
      neck. Both these values were significantly less than the reference mean values (P
      = 0.045 and < 0.001, respectively). Both current and long-term mean
      glucocorticoid doses showed significant negative correlations with BMD in the
      left femoral neck as well as in L2-4. Patients substituted with hydrocortisone
      were less often over-treated and had better BMD Z-score means than patients
      substituted with prednisone, prednisolone or dexamethasone. CONCLUSIONS: In the
      follow-up of patients with 21-hydroxylase deficiency, care needs to be exercised
      to keep the glucocorticoid substitution dose to a minimum. In most cases
      decreased bone mineral density is a result of over-substitution.

PMID- 9039337
TI  - A prospective study of psychiatric and psychological aspects of Cushing's
      syndrome.
AB  - OBJECTIVE: Cushing's syndrome is associated with psychiatric and psychological
      disturbances. The aim of this study was to ascertain the extent of mental illness
      in patients before and after treatment for Cushing's syndrome. DESIGN AND
      PATIENTS: Patients with Cushing's syndrome were identified for a prospective
      study. Control patients were selected with pituitary adenomas secreting GH or
      PRL. The aim was to reassess patients after Cushing's syndrome had been treated.
      MEASUREMENTS: Psychiatric symptoms were measured and classified using the Present
      State Examination (PSE), and analysed on the Catego Programme. The Hamilton
      Rating Scale (HRS) was used to measure depression. The Crown-Crisp Experiential
      Index was used to measure common psychoneurotic symptoms (anxiety, phobia,
      obsession, somatic, depression and hysteria scales). The Eysenck Personality
      Inventory was used to assess extroversion and neuroticism. Cortisol, ACTH, and
      other hormones were measured by conventional methods. Parametric and non
      parametric tests were used where appropriate. RESULTS: Catego analysis of
      psychiatric ratings showed only 8 patients of 43 with active Cushing's syndrome
      (19%) were normal. Psychiatric diagnoses were obtained as follows: neurotic
      depression in 20 (46%), possible neurotic depression in 1 (2%), reactive
      depression in 6 (14%), and non-specific neurotic symptoms in 8 (19%). Additional
      Catego ratings of suspected other psychoses were made for 3 patients who were
      also depressed. None of these 43 patients with active Cushing's syndrome had
      ratings of schizophrenia or mania, obsessional neurosis or pathological anxiety.
      In the control group 13 (87%) were normal, 1 patient with acromegaly had an
      anxiety state and one patient with a prolactinoma had neurotic depression. It was
      possible to reassess the Present State Examination after treatment in 25
      patients, when cortisol levels had been substantially reduced (to normal in 88%),
      the percentage rated as psychiatrically normal increased from 19 to 68 (chi 2 =
      11.7, 1 d.f., P < 0.01). Hamilton Rating Scale scores for depression showed
      significant improvements after treatment for Cushing's syndrome (mean decrease
      from 9.2 to 2.4, n = 36, P < 0.001). Crown-Crisp experiential index data showed
      significant improvements in anxiety, somatic symptoms, and depression (n = 25, P
      < 0.05). Eysenck Personality Inventory assessments showed a significant
      improvement in neuroticism score (n = 26 P = 0.016), but no significant change in
      extroversion (P = 0.5) or lie score (P = 0.6). CONCLUSIONS: Most patients with
      Cushing's syndrome had significant psychiatric pathology, usually depressive
      illness. As cortisol levels were returned to normal there were significant
      improvements in scores for depression and anxiety. Management of patients with
      Cushing's syndrome should include careful assessment of psychological and
      psychiatric illness.

PMID- 9039338
TI  - Size at birth and adrenocortical function in childhood.
AB  - OBJECTIVE: The mechanisms underlying the association between reduced size at
      birth and cardiovascular disease and non-insulin-dependent diabetes mellitus in
      adult life are not known. One possibility is that the intra-uterine environment
      has permanent effects on the function or activity of the hypothalamo-pituitary
      adrenal axis. We tested this by relating size at birth to the urinary excretion
      of adrenal androgen and glucocorticoid metabolites in a population sample of 9
      year-old children. SUBJECTS AND METHODS: One hundred and ninety children (89 boys
      and 101 girls) of known present height, weight and size at birth collected a 24
      hour urine sample. The urinary breakdown products of dehydroepiandrosterone
      sulphate and of cortisol and cortisone were measured by gas chromatography and
      their respective breakdown products summed ('adrenal androgen metabolites' and
      'glucocorticoid metabolites'). Excretion was expressed in microgram/day. RESULTS:
      Urinary adrenal androgen metabolite excretion was higher in children who had been
      light at birth. A 1-kg decrease in birthweight was associated with a 40% (95% CI
      9-79%) increase in metabolite excretion. Excretion was positively associated with
      current weight and age, but the relation with birth weight was independent of
      weight, age or sex. Urinary glucocorticoid metabolite excretion was positively
      associated with current weight, but not independently with age. The urinary
      excretion of total glucocorticoid metabolites was higher in children who had been
      light at birth, but the relation was best described as U-shaped, with the highest
      average urinary glucocorticoid metabolite excretion being found in children who
      had been either light or heavy at birth. The U-shaped (quadratic) relation
      persisted after adjustment for sex and current weight (P for quadratic term
      0.006). CONCLUSION: These findings suggests that the intra-uterine environment,
      as measured by fetal size at birth, has long-lasting effects on the function of
      the hypothalamo-pituitary-adrenal axis.

PMID- 9039339
TI  - Effects of oral and transdermal oestrogen replacement therapy on plasma levels of
      insulin-like growth factors and IGF binding proteins 1 and 3: a cross-over study.
AB  - OBJECTIVE: Conflicting results have been reported on the effects of oral and
      transdermal oestrogen replacement therapy on IGF-I, while little information
      exists regarding the effects on IGFBP -1 and -3. In this study we evaluated the
      effects of oral and transdermal oestrogens on these parameters in post-menopausal
      women in a randomized cross-over study. PATIENTS: A group of 14 post-menopausal
      women were randomized to receive progestin-opposed oestrogen replacement therapy
      administered orally (Trisekvens Novo: 17 beta-oestradiol 2 mg daily on days 1-22
      and 1 mg daily on days 23-28, norethisterone 1 mg days 13-22) or transdermally
      (Estracomb CIBA: oestradiol 50 micrograms/24 h on days 1-28, norethisterone 250
      micrograms/24 h on days 15-28) for 6 months after which they were crossed over to
      the alternative treatment option. Fasting blood samples were obtained before
      treatment, and after 3, 6, 9 and 12 months on treatment. MEASUREMENTS: IGF-I, IGF
      II, IGFBP-1, IGFBP-3, oestradiol and norethisterone were analysed by radioimmuno
      assays. In addition, IGFBPs were evaluated with Western ligand blots (WLB) in a
      subgroup of 12 patients. RESULTS: Plasma levels of oestradiol were not
      significantly different during oral and transdermal treatment. Norethisterone
      levels were below the detection limit in all situations in 8 patients, while 6
      patients had detectable levels in one or several samples during treatment. Oral
      treatment caused a significant decrease (16%, P < 0.005) in IGF-I and a non
      significant decrease in IGFBP-3. A similar effect was observed when samples
      containing detectable levels of norethisterone were excluded from the analysis.
      No significant effect on IGFBP-1 was observed when all samples were included in
      the analysis. However, when samples with detectable norethisterone were excluded
      IGFBP-1 increased by 46% (P < 0.01) during oral therapy. Contrary, transdermal
      treatment with oestrogens did not influence any of the parameters measured. None
      of the treatments had any effect on plasma IGF-II levels or IGFBP profile
      evaluated by WLB. CONCLUSIONS: Treatment with oral hormone replacement therapy
      significantly suppresses plasma IGF-1 levels and increases plasma IGFBP-1 while
      transdermal treatment had no influence. This may be due to the route of
      administration, as plasma oestradiol levels showed little difference between the
      groups. The effect of oral oestrogens on IGFBP-1 seems to be attenuated by
      progestins.

PMID- 9039340
TI  - Clinical and biochemical investigations and molecular analysis of subjects with
      mutations in the androgen receptor gene.
AB  - OBJECTIVE: Androgen insensitivity syndromes (AIS) in subjects with 46, XY
      karyotype and normal or even elevated androgen blood levels are characterized by
      various aberrations in male differentiation and virilization. AIS is often
      accompanied by a broad spectrum of abnormal binding characteristics of the
      androgen receptor (AR). In order to investigate the correlation between the
      degree of virilization defect and the type of androgen binding abnormalities
      and/or the nature of the mutation in the AR gene, we determined androgen binding
      characteristics of the AR protein and the sequence of the AR gene in clinically
      and biochemically well characterized patients with various degrees of androgen
      resistance. DESIGN AND PATIENTS: The activity of 5 alpha-reductase and the
      binding of androgen to its receptor (KD-values, Bmax, thermolability) were
      determined in genital skin fibroblasts from 20 patients with various degrees of
      defects in virilization (2 CAIS, complete AIS; 18 PAIS, partial AIS patients).
      The AR gene of these 20 subjects was characterized by PCR-SSCP analysis. In case
      of aberrant electrophoretic mobility the corresponding exon was sequenced.
      RESULTS: The 2 patients with CAIS and 7 with PAIS showed a mutation in the AR
      gene. In two, the mutation was in the DNA binding domain, and in all others in
      the ligand binding domain. In 11 patients with severe virilization defects no
      abnormal behaviour was detected in the PCR-SSCP. Transcriptional activation
      studies of two mutant ARs revealed that an approximately tenfold higher androgen
      concentration (methyltrienolone) is necessary to achieve maximal response as
      compared to the wild type AR. CONCLUSIONS: There is no obvious relation between
      the degree of androgen resistance and the binding parameters of the AR and/or the
      nature of mutation in the AR gene. Androgen insensitivity syndrome can occur
      despite normal androgen binding and presumably non-mutated AR genes. Even if
      there is abnormal binding of androgen and/or a mutation in the AR gene there is
      no clear-cut relationship between these parameters and the degree of virilization
      defects. Thus, in a proportion of patients, neither the determination of binding
      parameters of the AR nor the detection of mutations in the AR gene are sufficient
      to understand the mechanisms underlying the androgen insensitivity syndrome.

PMID- 9039341
TI  - Circulating inhibins and activin A during GnRH-analogue down-regulation and
      ovarian hyperstimulation with recombinant FSH for in-vitro fertilization-embryo
      transfer.
AB  - OBJECTIVE: We have investigated serial changes in plasma concentrations of
      inhibin A, inhibin B, pro alpha C and activin A in women undergoing stimulation
      with recombinant FSH in 'long-protocol' down-regulated cycles of IVF treatment.
      DESIGN: Blood samples were collected during the entire IVF treatment cycle at
      points coinciding with the early follicular phase of the cycle preceding
      treatment, pituitary down-regulation, stimulation with recombinant FSH, ovulatory
      triggering, and the luteal phase of the cycle. In patients who achieved
      conception, blood samples were also taken during the first 2 weeks of pregnancy.
      All samples were analysed for inhibin A, inhibin B, pro alpha C, activin A and
      oestradiol. PATIENTS: Fifteen women with normal ovarian function undergoing IVF
      treatment with tubal factor, mild endometriosis or idiopathic infertility.
      RESULTS: During pituitary desensitization, both inhibin A and inhibin B were
      significantly (P < 0.001, P = 0.002, respectively) reduced whereas levels of pro
      alpha C and activin A were largely unaltered. Levels of both inhibins rose
      markedly (P < 0.01) during FSH stimulation and a further rise in inhibin A was
      detected on the day after ovulatory trigger. Levels of both inhibin A and inhibin
      B then fell during and after oocyte pickup and continued to fall during the
      luteal phase. Activin A levels rose less markedly during gonadotrophin
      stimulation. Statistical analysis showed a high degree of correlation between the
      number of follicles (> 10 mm) and serum inhibin A (r = 0.65, P < 0.01) and pro
      alpha C (r = 0.65, P < 0.01) concentrations during the late follicular phase.
      CONCLUSIONS: These results indicate that ovarian production of dimeric inhibin A
      and B are gonadotrophin dependent, whereas activin A may have a significant
      gonadotrophin independent or extra-gonadal source. Inhibin A and pro alpha C may
      be useful markers for monitoring the effects of gonadotrophin stimulation.

PMID- 9039342
TI  - Decreased nocturnal melatonin secretion in patients with Klinefelter's syndrome.
AB  - OBJECTIVE: We have recently demonstrated that GnRH deficient male patients have
      increased nocturnal melatonin secretion which decreases to normal levels during
      testosterone treatment. The results suggested that sex steroids, rather than LH,
      modulate pineal melatonin in an inverse fashion. The purpose of this study was to
      characterize circulating melatonin levels in untreated males with
      hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS). DESIGNS:
      Prospective, controlled. SUBJECTS: Eleven patients with Klinefelter's syndrome
      and seven controls. Patients were subdivided into two groups: (1) with low
      testosterone, and (2) with normal testosterone levels. MEASUREMENTS: Serum
      samples for melatonin concentrations were obtained every 15 minutes from 1900 to
      0700 h in a controlled light-dark environment. RESULTS: All patients had elevated
      FSH, LH and oestradiol (E2) levels. Mean (+/-SD) dark time nocturnal melatonin
      levels were significantly lower in low testosterone KS (92 +/- 19 pmol/l)
      compared with 146 +/- 42 pmol/l in normal testosterone KS and 179 +/- 59 pmol/l
      in controls (P < 0.02). A similar pattern was observed for the mean (+/-SD) peak
      melatonin levels (165 +/- 41, 236 +/- 59 and 293 +/- 89 pmol/l) in low
      testosterone KS, normal testosterone KS and controls, respectively (P < 0.01).
      Integrated nocturnal melatonin secretion values (AUC) were also lower in low
      testosterone KS (64 +/- 13) compared with 96 +/- 26 in normal testosterone KS and
      116 +/- 39 pmol/min 1 x 10(3) in controls (P < 0.02). The time of melatonin peak
      and the time of the nocturnal melatonin rise as well as the light-time mean (+/
      SD) serum melatonin levels were similar in all three groups. No correlations were
      found between melatonin and LH, FSH, or E2 levels. CONCLUSIONS: Melatonin
      secretion is decreased in male patients with low testosterone hypergonadotrophic
      hypogonadism whereas in normal testosterone Klinefelter's syndrome patients,
      melatonin secretory profiles are normal. The results suggest that the suppression
      of melatonin secretion in these patients is mediated by GnRH (either directly or
      indirectly) and/or oestradiol.

PMID- 9039343
TI  - In vivo imaging of pituitary tumours using a radiolabelled dopamine D2 receptor
      radioligand.
AB  - OBJECTIVE: Knowledge of the dopamine D2 receptor status of pituitary tumours may
      play a predictive role in differential diagnosis and therapeutic decisions. This
      study was performed to evaluate the value of pituitary dopamine D2 receptor
      scintigraphy with (S)-2-hydroxy-3-123I-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)
      methyl]benzamide (123I-IBZM) in the diagnostic evaluation of patients with
      pituitary tumours. DESIGN AND PATIENTS: Scintigraphy using 123I-IBZM was
      performed in 5 patients with PRL-secreting macroadenomas, 2 patients with PRL
      secreting microadenomas, 17 patients with clinically non-functioning pituitary
      adenomas (NFPAs), 12 patients with GH-secreting adenomas and 1 patient with a TSH
      secreting macroadenoma. RESULTS: Single-photon emission tomography (SPECT) showed
      significant uptake of 123I-IBZM in the pituitary region in 3/5 macroprolactinoma
      patients. These results closely correlated with the response of plasma PRL levels
      to the dopamine D2 receptor agonist quinagolide. In two scan-positive
      prolactinoma patients, repeated SPECTs during therapy with quinagolide showed a
      reduction in the pituitary uptake of 123I-IBZM. Pituitary SPECT was negative in
      the 2 microprolactinoma patients, who responded to quinagolide administration. In
      4/17 patients with NFPA, significant uptake of the radioligand in the pituitary
      region was observed. In 2/3 scan-positive NFPA patients, who were treated with
      quinagolide, shrinkage of the pituitary tumours was observed. Treatment with
      quinagolide resulted in stabilization of tumour growth in the other scan-positive
      patients. Four out of 17 patients with NFPA and a negative SPECT were treated
      with quinagolide. Tumour growth was observed in 1 patient, and tumour size did
      not change in the other 3 patients. The pituitary region of none of the 12
      acromegaly patients showed significant uptake of 123I-IBZM. Sensitivity of the GH
      secreting adenomas to quinagolide was demonstrated in 8/12 patients in vivo by an
      acute test, and in 6/9 of the tumours in vitro. Pituitary SPECT was negative in
      the patient with the TSH-secreting macroadenoma and this tumour also showed no
      sensitivity to quinagolide in vivo or in vitro. CONCLUSIONS: We conclude that
      123I-IBZM is a ligand for in vivo imaging of dopamine agonist- sensitive
      macroprolactinomas, but not for microprolactinomas or GH-secreting adenomas. The
      technique potentially provides a means of predicting the dopamine agonist
      responses of non-functioning pituitary adenomas in vivo.

PMID- 9039344
TI  - Low-dose growth hormone replacement lowers plasma leptin and fat stores without
      affecting body mass index in adults with growth hormone deficiency.
AB  - OBJECTIVE: The ob gene product, leptin, is considered to be a marker of adipose
      tissue mass and a possible homeostatic regulator of body mass. Our objective was
      to examine the effect of GH replacement on adipose tissue stores and leptin in
      adult hypopituitarism. SUBJECTS: Twenty adults, mean age 47 years (range 20-69)
      with proven GH deficiency were randomly allocated to either GH (up to 0.25
      U/kg/week in daily doses) or placebo for 3 months before cross-over to the
      opposite treatment. MEASUREMENTS: Body composition was measured by dual-energy X
      ray absorptiometry (DEXA) in the whole body, trunk and limbs. Plasma leptin was
      measured by radioimmunoassay at baseline and +2, +4, +8 and +12 weeks in each
      treatment arm. RESULTS: Total body tissue fat (mean +/- SE) was 30.1 +/- 2.2%
      after GH compared with 31.9 +/- 2.2% after placebo, P < 0.001 (ANOVA). There were
      no significant changes in BMI (kg/m2), 29.1 +/- 1.3 after placebo vs 28.8 +/- 1.2
      after GH; or waist to hip ratio (WHR), 0.91 +/- 0.01 after both placebo and GH.
      Baseline plasma leptin showed a significant correlation with baseline BMI, r =
      0.67, P < 0.005 and baseline percentage total body fat, R = 0.89, P < 0.001.
      Plasma leptin (adjusted by using baseline percentage total body fat as a
      covariate) showed a significant linear decrease with time on GH compared with
      placebo (P = 0.03, ANOVA). CONCLUSIONS: Plasma leptin and total body fat fall
      promptly in response to low-dose replacement of GH in GH-deficient subjects.
      Hormone-induced changes in leptin can occur in humans in the absence of change in
      body mass index.

PMID- 9039345
TI  - Cushing's syndrome secondary to ectopic ACTH secretion from a primary ovarian
      carcinoma.
AB  - We report a 63-year-old woman who presented with clinical and biochemical
      features of ACTH dependent Cushing's syndrome secondary to a primary ovarian
      carcinoma. The tumour produced very high levels of ACTH precursors, consistent
      with defective POMC processing.

PMID- 9039346
TI  - Implantable materials and infection.

PMID- 9039347
TI  - Pathophysiology of infection--a theoretical approach.
AB  - The manifestation of postoperative wound infection has a tri-factorial basis: the
      overall systemic trauma and the additional effects of premorbidity (age,
      diabetes, etc.), the local host damage resulting from both the accident and
      surgery, and the bacterial contamination of the wound. The first factor is only
      moderately open to intervention, however, the amount of local host damage caused
      during the operation can be influenced directly by the surgeon who must ensure
      that his operating techniques are non-aggressive and in line with current
      knowledge. The factor of the intraoperative bacterial inoculum can be modified by
      attention to hygiene. The latter two factors are in direct relation to the
      following two hypotheses: Every wound is able to tolerate some local host damage
      and some bacterial inoculum without manifestation of infection. The bacterial
      wound flora is the product of the bacterial invasion force and the local wound
      conditions. The bacterial wound flora and the local condition of the wound are
      interrelated. If either factor exceeds the tolerable threshold, infection will
      become manifest, i.e. there will be an uncontrollable proliferation of bacteria.
      The level of this breaking point may depend upon certain systemic host factors
      such as age, diabetes, or immunodeficiency. Consequently, the prevention of
      infection must focus simultaneously on minimizing the local bacterial inoculum
      and optimizing local wound conditions. Future studies should concentrate on
      identifying the exact nature of the individual factors promoting infection, their
      quantification, and their relative importance.

PMID- 9039348
TI  - Relevance, pathogenicity and virulence of microorganisms in implant related
      infections.
AB  - It is impossible to imagine modern medicine today without indwelling devices of
      various kinds. The time that these implants or prostheses remain in the patient's
      body can vary from a few hours, e.g. intravenous catheter, to his entire life,
      e.g. hip prosthesis, heart valve. Besides the indisputable use and advantages of
      this type of medical intervention for the patient, e.g. saving his life or
      improving its quality, the associated complications should not be overlooked. One
      of the most frequent and significant complications of implant surgery is the
      manifestation of infection in the tissue around the implant. That infection
      occurs is not surprising since the indwelling devices predispose to bacterial and
      mycotic infection on the one hand and impede its eradication on the other. The
      consequences of infection for the patient may mean the loss of regained mobility
      and independence, hospitalization for sepsis, or even death. Microbes per se are
      not necessarily pathogenic, however, there are numerous virulence factors which
      affect the degree of pathogenicity of the microorganisms. These include, for
      example, various enzymes, (e.g. catalase, hyaluronidase, collagenase and other
      proteases), and specific surface structures, e.g. the polysaccharide capsules of
      pneumococci or the lipopolysaccharides of Gram negative bacteria, and the
      production of bacterial toxins, e.g. leucozidin, streptolysine. The strategies
      which the pathogenic bacteria employ in their efforts to occupy the host include
      adherence, penetration and multiplication, antiphagocytosis and serum resistance,
      the formation of siderophores, antiimmunity, and cell and tissue damage. An
      attempt will be made here to present an overview of this multifactorial event in
      which the host obviously plays an important role.

PMID- 9039349
TI  - Metal implants and surface reactions.
AB  - A metal in living tissue is prone to corrosion. The interaction of the foreign
      body with the tissue involves the redox reaction (an electron exchange) at the
      interface, the hydrolysis (a proton exchange) of oxide-hydrates as products of
      corrosion, and the formation of metal-organic complexes in the electrolyte.
      Denatured tissue in contact with the foreign body is the consequence. But
      behaviour of metals is variable; gold, stainless steel and most other metals
      react as described while few others like titanium and tantalum do not. The
      absence of a foreign body effect of a chemical kind is, without doubt, favorable
      in terms of tissue susceptibility to infection in the presence of titanium.

PMID- 9039350
TI  - Infection after intramedullary nailing: an experimental investigation on rabbits.
AB  - The purpose of this study was to investigate three relevant aspects of
      intramedullary nailing in terms of their effect on the occurrence of local
      infection. In an infection model on the rabbit tibia, the following were
      compared: a hollow and a solid nail (Experiment I), a reamed with an unreamed
      technique (Experiment II), and a steel with a titanium nail (Experiment III). In
      order to minimize the number of animals required, a grouped sequential procedure
      combined with an "up and down" dosage technique was applied. Microbiological
      evaluation was both qualitative and quantitative. The results in Experiment 1 (n
      = 44) indicated an infection rate for the hollow nail (59%) almost double that of
      the solid nail (27%) (P < or = 0.05). Experiment II (n = 44) produced an
      infection rate of 50% for the unreamed technique compared to 64% for the reamed
      technique, a difference which, on the basis of the number of bacteria present,
      was also statistically significant (P < or = 0.05). In Experiment III (n = 44) an
      infection rate of 82% was recorded for the steel nail compared to 59% for the
      titanium nail (P < or = 0.05). The results of the three experiments are only
      partially comparable with each other because of the grouped sequential procedure
      and the different inocula used. Nonetheless it would seem that the dead space
      inherent in the design of the hollow nail represents a considerable risk with
      regard to the occurrence of local infection. Reaming the medullary cavity with
      the attendant reduction in local vascularity and necrosis and the lesser
      biocompatibility of steel compared to titanium may be additional risk factors
      which should not be overlooked.

PMID- 9039351
TI  - Infection after open reduction and internal fixation with dynamic compression
      plates--clinical and experimental data.
AB  - Infection rates for open reduction and internal fixation (ORIF) with the DCP in
      clinical studies are based on heterogeneous data on general risk factors and do
      not take into account the direct effect of the implant (material, design,
      surface, technique). The initial degree of bacterial contamination is generally
      unknown and the applied definition of the term infection is not mentioned. In our
      own prospective randomized clinical study including 281 cases of ORIF with the
      DCP (154 steel vs 127 titanium), the influence of the implant material on
      susceptibility to local infection was examined in relation to initial bacteria
      contamination (109 non-contaminated / 172 contaminated). Although in the group of
      contaminated DCPs the difference in the infection rates for stainless steel (sSt)
      and commercially pure titanium (cpTi) showed no statistical significance, a
      tendency was apparent. In an animal experiment, the lower rates of infection for
      c.p.Ti-DCP compared to sSt-DCP in the presence of a local bacterial challenge
      could be demonstrated with statistical significance. The need for further
      experimental research in the field of implant related local infection after ORIF
      will be discussed and strategies for further investigations proposed.

PMID- 9039352
TI  - The influence of the chemical composition and surface of the implant on
      infection.
AB  - The influence of the localization and size of orthopaedic implants on infection
      has been analyzed extensively, but the influence of implant shape and chemical
      composition has rarely been studied, and the influence of the surface has only
      been described in one single report. Several experimental studies have tried to
      compare the incidence of infection for different materials. PMMA usually appears
      as the implant material most prone to causing infection, while titanium (Ti) and
      cobalt-chromium (CoCr) are the materials most resistant to infection. On the
      polished surface of cylinders implanted in rabbit femora, it took 40 times more
      inoculum to produce a clinical infection than it took for porous CoCr implants.
      The polished surface implants required 2.5 times more inoculum than porous Ti to
      produce infection.

PMID- 9039353
TI  - The effect of surface roughness on fibroblast adhesion in vitro.
AB  - Adhesion of tissue cells to biomaterial implants is a major factor of their
      biocompatibility. Quantitative or qualitative adhesion measurements would
      therefore be useful in the screening of new implant materials. Results from a
      quantitative method of measuring the total cell adhesion area of cultured cells
      is presented. It is postulated that the more compatible the surface, the greater
      the amount of cell adhesion. Fibroblastic cells were cultured on discs of plastic
      (Thermanox), commercially pure titanium (ISO 5832/2) or steel (ISO 5832/1), as
      used in AO fixation plates. The cells were fixed, stained, embedded in resin and
      their discs removed. Backscattered electron (BSE) imaging in a scanning electron
      microscope displayed the stained cells within the unstained resin. Imaging at
      high beam energy allowed visualization of the entire cell. Low beam energy
      displayed the regions of cell contact with the substrate, i.e. the focal adhesion
      sites. Images were analyzed with an image analysis and measurement system which
      allowed the percentage of the cell area involved with adhesion to be calculated.
      Results show that the material roughness, with the materials and cells tested,
      does not affect the total amount of cell adhesion. Implant surface design to
      encourage cell adhesion and discourage bacterial adhesion is discussed.

PMID- 9039354
TI  - Myocardial contusion.

PMID- 9039355
TI  - The natural history of cold intolerance of the hand.
AB  - When cold intolerance occurs in the injured hand, it is persistent in the
      majority of cases (79 per cent). Statistically, there is a link between the
      development of cold intolerance and the incidence of early postoperative pain.
      Postoperative pain relief should be of high quality and may possibly prevent the
      onset of cold intolerance.

PMID- 9039356
TI  - A method of fasciotomy wound closure.
AB  - The indications and methods of fasciotomy for acute compartment syndrome have
      been well documented. There has not been much attention paid to postoperative
      care, especially the management of the open wound produced. The common practice
      is to cover the wound with a split-skin graft if there is any difficulty with
      attempted closure. The resultant appearance may not be acceptable to the patient
      nor may the need to stay in hospital while the skin graft heals. A method relying
      on the elasticity of the skin which can also be used in out-patients is
      described.

PMID- 9039357
TI  - Outcome of 'whiplash' neck injury.
AB  - Psychological factors have been alleged to be important in the course and outcome
      of 'whiplash' neck injury but there is little quantitative evidence. This study
      uses quantitative methods involving a prospective interview assessment to
      describe psychological and quality of life predictors, and 3 and 12 month
      outcome. Consecutive attenders to the Accident and Emergency department of a
      teaching district hospital with a clinical diagnosis of 'whiplash' neck injury
      were included and there were follow-up interviews at home. Neck symptoms were
      recorded, and there was a standard mental-state interview with added questions
      about post-traumatic symptoms and a semi-structured interview for disability and
      consequences for quality of life. There was a wide individual variation in course
      and outcome; the majority of subjects complained of persistent neck symptoms and
      a sizeable minority reported specific post-traumatic psychological symptoms
      (intrusive memory, phobic travel anxiety), similar to those described by patients
      suffering multiple injuries. Social impairment, including effects on travel, were
      considerable in one-quarter. Reports of persistent neck symptoms were not
      associated with any baseline psychological variables or with compensation
      proceedings; psychological factors appeared to be more important in determining
      the extent of social impairment. We conclude that travel, social and
      psychological morbidity is substantially greater than previously recognized.

PMID- 9039358
TI  - Open fractures and internal fixation in a major African hospital.
AB  - Between September 1992 and June 1994, 20 patients with 27 open fractures were
      treated at a major Ethiopian hospital by open reduction and internal fixation.
      Sixteen fractures were caused by gunshots, eight by road traffic accidents, two
      by direct blows, and one by a fall. Twenty-one fractures were stabilized with
      ASIF plates, and six with screws and wires. Five fractures out of 27 (18.5 per
      cent) developed infection postoperatively. In one case secondary wound infection
      subsided after wound excision and plate removal. In three others the implants
      were replaced by external fixators, in two of which the infection subsided and
      the patients left hospital without infection. The two remaining patients were
      treated for 4 1/2 months and 18 months respectively for chronic osteitis. Ten of
      the 15 patients without postoperative infection returned for follow-up. None of
      them had developed osteitis. The overall functional results were good.

PMID- 9039359
TI  - A survey of advanced trauma life-support training for trainees in acute surgical
      specialties.
AB  - There have been few published data describing the demand for and amount of
      Advanced Trauma Life Support (ATLS) training received by trainees in acute
      surgical specialties. We undertook a survey on aspects of ATLS training,
      questioning all senior house officers in accident and emergency (A & E) medicine,
      general surgery and orthopaedic surgery in the west of Scotland in January 1995.
      More general surgical trainees were ATLS trained than orthopaedic or A & E
      trainees. Ninety-seven per cent of respondents felt ATLS was essential training
      for FRCS. There were few problems gaining study leave for the courses, but
      concern was expressed regarding the long waiting lists. ATLS training is
      therefore thought to be essential for surgical trainees, and the number of ATLS
      courses needs to be increased to cope with the demand.

PMID- 9039360
TI  - Outcome after pelvic ring fractures: evaluation using the medical outcomes short
      form SF-36.
AB  - Fifty-five multiply injured patients with operatively treated unstable pelvic
      fractures were evaluated for patient-oriented outcome measures. Forty-six adult
      patients were eligible to complete the SF-36 medical outcome score and completed
      the SF-36 eight scale medical outcome score by postal questionnaire at a mean
      follow up to 2 years. The average Injury Severity Score of the eligible patients
      was 17.5. The average age of the patients was 32 years and 8 months. Fractures
      were classified by the Tile classification and there were 13 type B and 33 type C
      pelvic fractures. Seventy-six per cent of patients responded to the surgery.
      There was a 14 per cent impairment in physical outcome score and a 5.5 per cent
      impairment in mental outcome score compared with the normal population. The
      physical and mental outcome of multiply injured patients with pelvic fractures
      can be measured objectively.

PMID- 9039361
TI  - Chiropractic treatment of chronic 'whiplash' injuries.
AB  - Forty-three per cent of patients will suffer long-term symptoms following
      'whiplash' injury, for which no conventional treatment has proven to be
      effective. A retrospective study was undertaken to determine the effects of
      chiropractic in a group of 28 patients who had been referred with chronic
      'whiplash' syndrome. The severity of patients' symptoms was assessed before and
      after treatment using the Gargan and Bannister (1990) classification. Twenty-six
      (93 per cent) patients improved following chiropractic treatment (U = 34, P <
      0.001). The encouraging results from this retrospective study merit the
      instigation of a prospective randomized controlled trial to compare conventional
      with chiropractic treatment in chronic 'whiplash' injury.

PMID- 9039362
TI  - The effect of a rigid collar on intracranial pressure.
AB  - Spinal immobilization and the application of a rigid collar to protect the neck
      forms an integral part of care of the injured. The very nature of collar design
      predisposes to vascular obstruction of blood draining from the brain and
      theoretically may raise intracranial pressure (ICP). We analysed this effect
      prospectively in a series of injured patients using the Stifneck rigid collar,
      the most popular collar used in the UK. Comparison of the ICP before, during and
      after collar application showed a significant rise (P < 0.001), a mean rise in
      ICP of 4.5 mmHg, with a standard deviation of 4.1 mmHg. Insignificant changes in
      mean arterial pressure suggested that this effect is a response to distortion of
      venous drainage rather than cutaneous stimulation alone. Since head-injured
      patients with lowered level of consciousness form a key group who require
      cervical spinal immobilization it is essential that secondary insults producing
      raised ICP are minimized. Alternative forms of cervical spinal immobilization
      should be considered if collars impede venous drainage through the neck.

PMID- 9039363
TI  - Tibial reconstruction by ipsilateral vascularized fibular transfer.
AB  - Between 1979 and 1991 ipsilateral vascularized fibular transposition was
      performed on eight patients with segmental tibial defects following injury. We
      report these cases with a minimum follow-up of 2.5 years. All the tibial defects
      were the result of severe open fractures (Gustilo Grade III) and either bone loss
      or infected non-union, and ranged in size from 1 to 12 cm. The patients had an
      average of seven procedures and a delay of 33 months before fibular transfer. The
      procedure was successful in achieving fracture union in all cases, with an
      average time to union of 15 months (range, 5-33 months). Shortening of up to 3 cm
      and some residual ankle stiffness was found, but all patients were ambulating
      bearing full weight and six had returned to their previous occupation by their
      final follow-up. Only one patient had significant pain affecting function. This
      is a successful and relatively simple technique compared to microvascular and
      bone transport procedures for reconstructing segmental tibial defects with
      relatively avascular graft beds.

PMID- 9039364
TI  - Vertical deceleration injuries: a comparative study of the injury patterns of 101
      patients after accidental and intentional high falls.
AB  - We analysed the pattern of injury of 101 adult patients who were treated in our
      Trauma Center after a fall from an average height of 7.2 m between 1987 and 1990.
      In 62 patients the fall was accidental, and 39 jumped with suicidal intent. The
      most common injuries were fractures of the thoracic and lumbar spine (83.0 per
      cent) especially of the thoracolumbar junction. The pattern of limb injuries is
      towards a significant preference of the metaphyseal and epiphyseal parts of the
      bones of the distal joints (wrist, elbow, ankle, subtalar). Fractures of the
      diaphyseal areas and the proximal joints (shoulder, humerus, hip, femur) were
      rare. The incidence of thoracic (20.8 per cent) and pelvic injuries (30.0 per
      cent) was relatively lower. Blunt abdominal injury (5.9 per cent) was rare after
      a fall from a great height. Head injuries occurred in only 27 per cent of our
      patients who all survived their transport to hospital. There is no significant
      difference in injury patterns between deliberate and accidental falls, but there
      is a higher number of isolated injuries in all patients after unsuccessful
      suicidal jumps.

PMID- 9039365
TI  - Missed bilateral anterior fracture dislocations of the shoulder.

PMID- 9039366
TI  - Avascular necrosis of the head of femur after intramedullary nailing for fracture
      of the shaft of the femur.

PMID- 9039367
TI  - Ankle diastasis without fracture: an uncommon injury with an unusual
      complication.

PMID- 9039368
TI  - Closed rupture of the common peroneal nerve: an unusual sporting injury.

PMID- 9039369
TI  - Diagnosis of retrosternal dislocation of the clavicle with ultrasound.

PMID- 9039370
TI  - Traumatic transection of the intrapancreatic common bile duct due to blunt
      injury: a case report and literature review.

PMID- 9039371
TI  - Irreducible femoral neck fracture in a child.

PMID- 9039372
TI  - Blunt abdominal injuries. Diagnostic peritoneal lavage, ultrasonography and
      computed tomography scanning.

PMID- 9039373
TI  - The posterior Monteggia: a pathological lesion?

PMID- 9039374
TI  - Abortion, breast cancer, and impact factors--in this number and the last.

PMID- 9039375
TI  - The bibliographic "impact factor" of the Institute for Scientific Information:
      how relevant is it really for public health journals?

PMID- 9039376
TI  - Research into purchasing health care: time to face the challenge.
AB  - Purchasing health care is at the core of the reforms of the UK NHS and yet there
      is little research evidence on which the policy is based. Research in this area
      is hampered by a lack of clarity over the aims of purchasing and the pace of
      change within the NHS. Purchasing developments such as general practice fund
      holding are proceeding without a large scale evaluation of their impact. At a
      national level a research effort is required to investigate this key area of the
      NHS reforms.

PMID- 9039378
TI  - An appreciation of 'Studies on infant mortality' by Barnet Woolf.

PMID- 9039377
TI  - Studies on infant mortality--Part II. Social aetiology of stillbirths and infant
      deaths in county boroughs of England and Wales.

PMID- 9039379
TI  - Smoking habits and risk of fatal stroke: 18 years follow up of the Oslo Study.
AB  - STUDY OBJECTIVE: To examine the risk of fatal stroke in relation to smoking
      habits in men screened for the Oslo study. DESIGN: The Oslo study is a
      prospective, cohort study of the epidemiology and preventive aspects of
      cardiovascular diseases in middle aged men. Screening started in May 1972 and
      results after 18 years of follow up are reported. PARTICIPANTS: There were 16209
      men aged 40-49 years, of whom 16173 had no stroke history. Eighty five men died
      from stroke, of whom 48 were daily cigarettes smokers, 7 were pipe and cigar
      smokers, 15 smoked cigarettes and pipe or cigars daily, 11 were previous
      cigarette smokers, and 4 had never smoked cigarettes. MAIN RESULTS: Results of
      proportional hazards regression analysis adjusted for age, diastolic blood
      pressure, and glucose concentration showed the following rate ratios (RR) (95%
      confidence interval) of smoking groups compared with those who had never smoked
      or had previously smoked: combined cigarette and cigar or pipe smokers, RR = 6.1
      (3.0, 12.5); cigarettes only, RR = 4.1 (2.3,7.4); and pipe and/or cigars only RR
      = 2.2 (0.9,5.5). The overall, age adjusted risk of smoking cigarettes daily was
      3.5 and was found to increase with increasing cigarette consumption. Regardless
      of their smoking group, stroke cases had increased diastolic (DBP) and systolic
      blood pressure (SBP) when compared with men who had not had a stroke. The
      absolute differences in DBP and SBP between stroke cases and others for never and
      previous cigarette smokers versus daily smokers were twice as large: DBP, 12.1
      mmHg versus 6.5 mmHg respectively and SBP, 16.0 mmHg versus 7.1 mmHg
      respectively. A high BMI increased the risk of fatal stroke of never and previous
      cigarette smokers. Men being treated for hypertension at the time of screening
      had three times the crude risk of fatal stroke of men who were not taking
      hypertensive treatment. CONCLUSIONS: Daily cigarette smoking increased the risk
      of fatal stroke three and a half times. Combined cigarette and pipe or cigar
      smoking had a higher risk than smoking cigarettes only. An increased risk was
      found in relation to increased daily cigarette consumption.

PMID- 9039380
TI  - The sociodemographic pattern of tobacco cessation in the 1980s: results from a
      panel study of living condition surveys in Sweden.
AB  - STUDY OBJECTIVES: To analyse the factors that determined whether or not people
      were successful in quitting tobacco during the 1980s in Sweden. DESIGN: A
      logistic regression model was used for the analyses and included: education,
      marital status, socioeconomic group, social network, physical activities,
      cigarette consumption, and years spent smoking as independent variables. Men and
      women were analysed separately for smoking. A specific univariate analysis was
      also performed for men who used snuff. SETTING: Sweden. PARTICIPANTS: A panel of
      5104 randomised people aged 16-84 years was interviewed in 1980-81 and followed
      up in 1988-89 in the survey of living conditions undertaken by Statistics Sweden.
      The participation rate was 86%. The panel included 1546 men and women who were
      daily smokers. There were 418 daily users of snuff among the men, and 129 men
      both smoked and used snuff. MAIN RESULTS: Together 26% of women and 23% of men
      had quit smoking. Five percent in both groups were new smokers. Among men, 26%
      had quit using snuff and 5% had begun smoking. New snuff users among men were 5%.
      In the multivariate analysis, unmarried men kept smoking at significantly higher
      rates (OR 2.1; 95% CI 1.2,3.6), as did those men who smoked 11-20 cigarettes/day
      (OR 2.2; 95% CI 1.5, 3.4), or more than 20 cigarettes/day (OR 2.8; 95% CI
      1.4,5.7). Among women, smoking 11-20 cigarettes/day was also a significant factor
      (OR 3.3; 95% CI 2.1,5.0). Men and women aged 25-44 were significantly more likely
      to continue smoking (OR = 2.1; 95% CI 1.1,3.7, and 2.2; 95% CI 1.2,4.4) as were
      those who had smoked for 20 years or more (OR 4.7; 95% CI 2.0,10.8 and OR 2.5;
      95% CI 1.1,5.5, respectively). For women, low education (up to grade 9) was also
      a significant factor (OR = 2.5; 95% CI 1.2,5.1). Among men who had quit using
      snuff we did not find any values of significance. CONCLUSIONS: One in four
      smokers had quit during the 1980s and a few started smoking (5%). Some men quit
      smoking and started using snuff instead. For both sexes, the daily consumption of
      cigarettes, years spent smoking, and age were the most important determinants of
      successful quitting. In men, being married/ cohabiting was an important factor as
      was higher education in women.

PMID- 9039381
TI  - Respiratory health effects of industrial air pollution: a study in east
      Lancashire, UK.
AB  - STUDY OBJECTIVE: To determine whether there was a higher incidence of respiratory
      ill health in children living near to a cement works than in those from a
      different area, and if so whether the higher incidence was due to the use of a
      hazardous waste-derived fuel at the works. STUDY DESIGN: A sample of the
      population of children living near the cement works (the study area) was compared
      with a sample of children living between 9 and 19 km away from the site (the
      control area). SETTING: The cement works is located on the north eastern edge of
      a small rural town in east Lancashire. METHODS: Data were collected via the use
      of a health questionnaire. This was distributed through selected primary schools
      to families who had one or more children of primary school age (5-11 years). MAIN
      RESULTS: The study and control populations were comparable in terms of response
      rates, gender, and socioeconomic indicators. There was no significant difference
      in the incidence of asthma (as diagnosed by a general practitioner) between the
      two areas when adjustment for hayfever was made. The incidence of sore throat was
      significantly higher in the case area, a difference not explained by other
      factors. For two other non-specific indicators of respiratory health (blocked
      nose and sore eyes) there was a significantly higher incidence in the study area,
      although hayfever and mould were also significant influences. CONCLUSIONS: The
      results indicated that certain non-specific health indicators were more common in
      the children living near a cement works. This excess may be due to exposure to
      emissions from the site. However, it is not possible to draw firm conclusions
      because there are no epidemiological data predating the use of the hazardous
      waste derived fuel.

PMID- 9039382
TI  - The influence of alcohol consumption on worldwide trends in mortality from upper
      aerodigestive tract cancers in men.
AB  - STUDY OBJECTIVES: To assess current trends in male mortality from cancers of the
      oral cavity/pharynx, oesophagus, and larynx (upper aerodigestive tract cancers),
      and relate these to past national consumption of alcohol and smoking of
      cigarettes. To assess the impact of current trends in alcohol consumption and
      tobacco smoking on likely future rates of these cancers. DESIGN: Mortality data
      for cancers of the oral cavity/pharynx, oesophagus, and larynx were obtained for
      the years 1955-89 in 25 countries located in North America, Australasia, Europe,
      and Japan. Information on past and current alcohol consumption was also obtained
      for these countries, while current national lung cancer rates were used as a
      proxy measure of past smoking levels. SETTING: The World Health Organization
      mortality database. MAIN RESULTS: National death rates from cancers of the oral
      cavity/pharynx, oesophagus, and larynx (considered together) are currently
      increasing among men and are most strongly associated with the level of per
      capita consumption of alcohol 20 years previously. They were less strongly
      associated with the level of alcohol consumption 10 years ago, and only very
      weakly associated with the current level of lung cancer mortality (a marker of
      past smoking habits). Regression analysis showed that the national rate of upper
      aerodigestive tract cancer could be estimated using information on past alcohol
      consumption and an interaction term between alcohol consumption and current lung
      cancer rates. Assuming stability in rates of lung cancer, the sizeable increase
      in alcohol consumption from 5 to 10 litres per capita each year that occurred in
      some countries during the 1960s and 70s means that increases of around 5 per
      100,000 in the death rate from these cancers can be expected in these countries
      in the next decades. CONCLUSIONS: Previous alcohol consumption in a country is a
      strong predictor of deaths from cancers of the upper aerodigestive tract in men,
      and current increases in death rates can probably be related to increases in
      consumption which took place during the 1960s and 70s. Combined with a reduction
      in tobacco smoking, which is already taking place in some countries, reversing
      the trend of increases in consumption of alcohol has the potential for a sizeable
      impact on the burden of these cancers.

PMID- 9039383
TI  - Socioeconomic circumstances and the risk of bowel cancer in Northern Ireland.
AB  - OBJECTIVE: To describe the variation in the incidence of colorectal cancer across
      Northern Ireland and relate it to factors associated with community deprivation.
      DESIGN: This was a cross sectional descriptive study. SETTING: Incidence data
      were obtained from a population based register for the period 1990-91. Small
      areas were characterised by their "affluence", or lack of it, by deriving a
      Townsend deprivation score for each electoral ward, using information from the
      1991 census. PARTICIPANTS, MAIN OUTCOME MEASURES, AND STATISTICAL METHODS: The
      age standardised incidence was calculated for all colorectal cancer cases
      diagnosed histologically in 1990-91. Electoral wards were grouped into quintiles
      of the population after ranking of their Townsend scores and the association with
      incidence was studied using Poisson regression. RESULTS: The age standardised
      colorectal cancer incidence ranged from 22.5 (for quintile 1) to 29.9/100,000
      (quintile 5) for men but the trend for women was less regular and rates were
      18.4, 23.8, 27.3, 26.5, and 23.9/100,000 for quintiles 1-5 respectively (that is,
      from the most "affluent" to the most "deprived" fifths of the population). After
      adjusting for age and sex in Poisson regression, there was a significant
      association between the total colorectal cancer incidence and levels of community
      deprivation. The rate ratio for the most deprived quintile of the population
      (compared with the least) was 1.28 (95% CI 1.06,1.53). The effect was stronger
      for rectal cancer than for colonic cancer. There was no association between
      community deprivation and the cancer stage at diagnosis. CONCLUSIONS: In this
      population, the colorectal cancer incidence is associated with the level of
      material deprivation. The disease stages at the time of diagnosis in patients
      from more deprived areas seem to be comparable with those of patients from
      affluent areas. As others have shown, associations such as these are not
      explicable entirely on the basis of the distribution of known risk factors.
      Further research is needed to determine plausible mechanisms for the association.

PMID- 9039384
TI  - The sex ratio of children in relation to paternal preconceptional radiation dose:
      a study in Cumbria, northern England.
AB  - STUDY OBJECTIVE: To investigate whether the occupational exposure to external
      ionising radiation of men employed at the Sellafield nuclear installation, West
      Cumbria, affects the sex of the children they subsequently father. DESIGN: A
      retrospective cohort study using logistic regression to analyse the sex ratio, in
      particular in relation to paternal preconceptional irradiation. SETTING AND
      PARTICIPANTS: The 260,060 singleton births between 1950 and 1989 to mothers
      resident in Cumbria, north west England. RESULTS: The sex ratio among children of
      men employed at any time at Sellafield was 1.094 (95% CI: 1.060, 1.128),
      significantly higher than that among other Cumbrian children, 1.055 (95% CI:
      1.046, 1.063). There was an increased sex ratio of 1.396 (95% CI: 1.127, 1.729)
      in the 345 children whose fathers were estimated from annual dose summaries to
      have received more than 10 mSv of external radiation in the 90 days preceding
      conception, but no significant linear trend between sex ratio and 90 day paternal
      preconceptional dose was found. There was no significant association between sex
      ratio and the external dose accumulated before the 90 day period preceding
      conception. CONCLUSIONS: Men employed at Sellafield fathered a greater proportion
      of boys than would be expected for a Cumbrian population, which may be partly
      explained by their younger age distribution. A greater effect was observed in the
      fathers with recorded doses exceeding 10 mSv in the 90 days before conception.
      While this may reflect a true statistical association, it is also possible that
      it may be a chance finding due to imprecision in the dose estimates and
      consequent misclassification.

PMID- 9039385
TI  - Total and occupationally active life expectancies in relation to social class and
      marital status in men classified as healthy at 20 in Finland.
AB  - STUDY OBJECTIVE: To study differences in total life expectancy and in
      occupationally active life expectancy in relation to social class and marital
      status in men classified as healthy as young adults. DESIGN: Historical cohort
      study. SETTING: Finland. PARTICIPANTS: Altogether 1662 men classified as
      completely healthy at the time of induction to military service (mean birth year
      1923), who had been selected as referents for a study of former athletes. Mean
      follow up time was 46 years. MEASUREMENTS: Vital status was determined by follow
      up through local parish data up to 1990. Mortality data were obtained from the
      Cause of Death bureau of the Central Statistical Office of Finland. Occurrence of
      work disability was assessed from nationwide disability pension register data.
      Mean total life expectancy and mean occupationally active life expectancy (end
      points disability pension or death before age 65 years) were estimated. Social
      class was based on the major lifetime occupation, while marital status was
      classified as "never married" or "ever married" at the end of follow up. MAIN
      RESULTS: Mean total life expectancy was highest among executives and managers
      (73.2 (95% confidence interval (CI): 70.3, 76.1) years), next highest in clerical
      (white collar) workers (72.0 (70.0, 74.1) years), and lowest in unskilled blue
      collar workers (63.65 (61.1, 66.2) years). Skilled workers and farmers were
      intermediate. For the occupationally active life expectancy estimates, a similar
      gradient was observed: highest for executives (61.9 (60.7, 63.1) years) and
      lowest for the unskilled (52.2 (50.2, 54.2) years). The ratio of occupationally
      active life expectancy to total life expectancy was highest for executives (85%)
      and lowest for farmers (81%) and unskilled workers (82%). CONCLUSIONS: The social
      class gradient known to exist for mortality is also present for occupational
      disability. Social class and marital status differences in mortality are already
      evident in early adulthood and continue into old age. Those with the highest life
      expectancy also have the largest proportion of their life span free of
      occupationally incapacitating disability.

PMID- 9039386
TI  - Menarche and the onset of depression and anxiety in Victoria, Australia.
AB  - STUDY OBJECTIVE: Psychiatric disorder often begins at adolescence. This study
      aimed to examine the associations between puberty and social circumstances and
      the adolescent rise in depression and anxiety. DESIGN: A two stage cluster
      sampling procedure was used to identify a representative group of Australian
      secondary school students in years 7 (age 12-13 years), 9 (14-15 years), and 11
      (16-17 years) of 45 Victorian schools. The computerised clinical interview
      schedule (CIS) was used to evaluate psychiatric morbidity. MAIN RESULTS: A total
      of 2525 subjects completed the survey - an overall participation rate of 83%.
      Levels of depression and anxiety increased with the secondary school years and
      girls had significantly higher rates at each school year level. For boys, the
      clearest independent associations with depression and anxiety were rising school
      year level and high parental educational achievement. For girls menarchal status
      emerged as the strongest predictor. Associations with age and school year level,
      evident on univariate analysis, did not persist when the recency of menarche was
      taken into account. After addition of measures of perceived social stress to a
      multivariate model, a significant association between depression/anxiety and
      parental divorce disappeared but the association with menarche persisted.
      CONCLUSIONS: Menarche marks a transition in the risk of depression and anxiety in
      girls. The pattern of findings is consistent with a biological mediation of this
      association.

PMID- 9039387
TI  - Targeted hepatitis B vaccination--a cost effective immunisation strategy for the
      UK?
AB  - OBJECTIVE: To compare the potential cost effectiveness of vaccination against
      hepatitis B virus (HBV) targeted at genitourinary clinic (GU) attendees with that
      of universal infant vaccination. DESIGN: A mathematical model of sexual and
      perinatal transmission of HBV was used to compare the effectiveness among
      heterosexual and homosexual populations of programmes of mass infant vaccination
      and targeted immunisation of genitourinary medicine (GU) clinic attendees. Each
      was applied to 90% of the eligible population with differing assumptions about
      rates of compliance and seroconversion - problems of delivery (obtaining high
      compliance) was considered a significant drawback of targeted vaccination.
      Observed relationships between GU clinic attendance and sex partner change rates
      for heterosexuals and for homosexuals were used to define the rates of
      vaccination uptake within sexual activity risk groups. SETTING: England and
      Wales. RESULTS: Model results showed that for heterosexuals universal infant
      vaccination became more effective than clinic based vaccination only
      approximately 40 years after the start of the programme and that the predicted
      cost effectiveness of GU clinic vaccination was greater at all times. For
      homosexuals, clinic vaccination was always more effective over the time frame
      considered, but by 50 years if it were carried out without prior screening it had
      become appreciably less cost effective than a mass infant programme. With prior
      screening in GU clinics this cost effectiveness deficit was only marginal.
      CONCLUSIONS: Targeted vaccination might have a much greater potential than is
      realised at present, particularly if it were possible to improve compliance of
      clinic attendees. A fuller comparison between mass infant and targeted
      vaccination must await the specific inclusion in the model of other risk groups
      such as intravenous drug users. An important determinant of the relative merits
      of the two approaches is the relationship between rates of attendance and of
      changing sexual partners. Further research on this is required.

PMID- 9039388
TI  - Reliability of data from proxy respondents in an international case-control study
      of cardiovascular disease and oral contraceptives. World Health Organization
      Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
AB  - STUDY OBJECTIVES: To evaluate the reliability of data supplied in a case-control
      study by proxy respondents for cases who were too ill to do so themselves.
      DESIGN: A hospital based, case-control study of the current use of oral
      contraceptives (OC) and cardiovascular diseases. Data from "true" controls
      matched to a subset of cases were compared with those supplied by proxy
      respondents about the true controls. SETTING: Hospitals in 21 centres from
      Africa, Asia, Europe, and Latin America. PATIENTS AND PARTICIPANTS: For a subset
      of cases, 403 pairs of controls-one "true" and one proxy-were interviewed. "True"
      controls were matched by age, place, and time of admission and were admitted with
      1 of 27 permissible diagnoses not associated with OC use. Proxy controls were
      either relatives or friends of true controls. MAIN RESULTS: Levels of concordance
      between data from proxy and true controls were high for most variables regarding
      recent events, including current OC use, but were greatly diminished when
      detailed information, particularly from the past, was required. Husbands were
      usually the best proxy, although this was question-specific. The sensitivity and
      specificity of proxy responses were 93% (95% confidence intervals: 77%, 99%) and
      100% (98%, 100%) respectively, for current use of OC. Assuming the
      misclassification of current OC use by proxy cases is similar to that produced by
      proxy controls, the estimated impact of using proxy data on risk estimates
      associated with current OC use was to bias the overall estimate of risk of stroke
      by less than 3% and the risks of both acute myocardial infarction and venous
      thromboembolism by less than 1%. CONCLUSIONS: Friends or relatives, and
      particularly husbands, provided reliable information when used as proxy
      respondents for young women. The estimated impact of misclassification by proxy
      respondents on overall risk estimates in the WHO collaborative study was less
      than that which would have arisen if information from proxy respondents had not
      been used.

PMID- 9039389
TI  - Standardisation or modelling of mortality rates.
AB  - STUDY OBJECTIVE: To compare the results obtained when estimating a standardised
      rate using the conventional technique of stratified analysis and using Poisson
      regression, and to evaluate the speed of the two techniques in making the
      calculation. DESIGN: Cross sectional study. SETTING AND PARTICIPANTS: The trend
      in motor vehicle accident mortality in males from 1985 to 1992 in Spain was
      compared using stratified analysis and Poisson regression. In the stratified
      analysis the calculations were made using a specially designed spreadsheet while
      in the Poisson regression the statistical program used was EGRET. RESULTS: The
      stratified analysis took two hours and the Poisson regression 15 minutes to
      complete. In the stratified analysis a single estimate for each year was
      obtained, whereas the model of Poisson regression that best fitted the data
      included an interaction term between age and year. CONCLUSION: Poisson regression
      can be considered a serious alternative to stratified analysis when the objective
      is to compare mortality rates standardised by one or two variables.

PMID- 9039390
TI  - Use of mid-arm and chest circumferences to predict birth weight in rural north
      India.
AB  - STUDY OBJECTIVE: To determine the most appropriate surrogate indicator and its
      cut off point for identifying low birthweight babies in northern India. STUDY
      SETTING: A secondary level hospital at Ballabgarh. The patients were from nearby
      rural and urban areas and mostly belonged to lower and middle socioeconomic
      strata. PARTICIPANTS: These comprised 733 singleton newborns delivered in the
      hospital between April and December 1991. DESIGN: Birth weight, arm
      circumference, and chest circumference were measured in all the newborns.
      Different cut off points for each index were identified and their validity was
      tested. Based on the regression equations, a simple chart was drawn up and was
      used to predict weights for different arm and chest circumferences in the
      hospital and community settings. MAIN RESULTS: Cut off points for arm and chest
      circumferences of 8.5 cm and 29.5 cm respectively gave a sensitivity and
      specificity of around 80%. When the chart based on the regression equations was
      tested in both the hospital and the community, chest circumference was found to
      be the better of the two indicators. CONCLUSION: Chest circumference seems to be
      the most appropriate surrogate measure for birth weight. Cut off points of 29.5
      cm and 27.5 cm seem to be satisfactory for predicting birth weight below 2500 g
      and 1800 g respectively. The birthweight prediction card using chest
      circumference was effective in predicting birth weight.

PMID- 9039391
TI  - Smoking and alcohol consumption in Trent, UK: an analysis of item non-response.

PMID- 9039392
TI  - Do sexual health questions alter the public's response to lifestyle
      questionnaires?

PMID- 9039393
TI  - Use of deprivation indices in small area studies.

PMID- 9039394
TI  - The decline in sex ratios at birth, England and Wales, 1973-90.

PMID- 9039396
TI  - A new model for discrete character evolution.
AB  - The paper provides an explicit justification for the principle that a uniform
      taxon should contribute only one datapoint in comparative analyses with discrete
      variables. The justification is that phylogenetic patterns in variables
      unincluded in the proposed test vitiate the assumption of independence, both at
      the level of species and at the level of branch segments. The consequence is that
      a uniform taxon cannot safely be counted as more than one datapoint. The
      arguments use a branching discrete Markov process in continuous time, with the
      new feature that the tested variables are only a subset of the evolving
      characters. This model is proposed as a useful criterion for measuring the merit
      of proposed tests, and illustrates the necessity for models in evaluating
      comparative methods.

PMID- 9039395
TI  - A note on the interpretation of tracer dispersion in the liver.
AB  - The transit time distribution of intravascular markers and highly diffusible
      solutes is determined by the mixing process within the network of interconnected
      sinusoids. Based on the role of the relative dispersion or coefficient of
      variation (CV2) of transit times as a measure of distribution dynamics
      (macromixing) various intrahepatic mixing processes are discussed, which are
      implied by current models of hepatic elimination. The opposite extremes of
      perfect micromixing and complete segregation are reflected by the dispersion
      model and the distributed parallel tube model, respectively. Assuming various
      capillary structures-including that of a fractal network-the dispersion models
      differ with regard to the predicted scaling behaviour of CV2. The observed flow
      independence of CV2 suggests that molecular diffusion and Taylor dispersion can
      be neglected but does not allow discrimination between mixing models.

PMID- 9039397
TI  - Is DNA a language?
AB  - DNA sequences usually involve local construction rules that affect different
      scales. As such their "dictionary" may not follow Zipf's law (a power law) which
      is followed in every natural language. Indeed, analysis of many DNA sequences
      suggests that no linguistics connections to DNA exist and that even though it has
      structure DNA is not a language. Computer simulations and a biological approach
      to this problem further support these results.

PMID- 9039398
TI  - The design of adaptive systems: optimal parameters for variation and selection in
      learning and development.
AB  - Some aspects of learning and development are based on evolutionary change within
      the organism. In trial and error learning, variant ideas or behaviors are
      generated and selective filters (learning rules) choose among the population of
      variants. Development may, in some cases, proceed by selection within a
      population of variant cellular lineages. This paper analyses abstract properties
      of selective systems to understand the evolutionary dynamics that occur within
      organisms. The Price Equation and Fisher's fundamental theorem of natural
      selection, two of the most powerful concepts in evolutionary genetics, are
      applied in a general way to internal selective systems in learning and
      development. This analysis emphasizes generative mechanisms and selective filters
      as genetically controlled phenotypes of individual organisms. Generative
      mechanisms create the variation on which selection acts. Selective filters
      determine the extent to which selection within the organism optimizes organismal
      performance. The methods of Price and Fisher provide a general way in which to
      partition evolutionary change into improvements caused by selection and the
      tendency of high performance variants to deteriorate because of competition or
      environmental change. This balance between selective improvement, at a rate equal
      to the variance in fitness, and a matching deterioration in performance, provides
      general insight into the common properties of adaptive systems in genetics,
      learning and development. These ideas are applied to a model of honey bee
      foraging. This example clarifies the relation between genes and phenotypes
      controlled by internal selective systems.

PMID- 9039399
TI  - Chaos in weakly-coupled pacemaker cells.
AB  - A model of the rabbit sinoatrial action potential is introduced, based on a model
      by Morris & Lecar. One cell is described by two nonlinear first-order ordinary
      differential equations, with ten constant parameters. The model is much simpler
      than most other models in use, but can reproduce perfectly experimentally
      recorded action potentials. The dynamics of two coupled cells, with and without
      the presence of periodic acetylcholine pulses, shows examples of bifurcations and
      strange attractors, mathematical phenomena characterizing chaotic motion. It
      remains to be clarified whether such dynamics is actually observed, for example
      in the small irregular variations of the normal heart rate.

PMID- 9039400
TI  - Percolation on the fitness hypercube and the evolution of reproductive isolation.
AB  - We study the structure and properties of adaptive landscapes arising from the
      assumption that genotype fitness can only be 0 (inviable genotype) or 1 (viable
      genotype). An appropriate image of resulting ("holey") fitness landscapes is a
      (multidimensional) flat surface with many holes. We have demonstrated that in the
      genotype space there are clusters of viable genotypes whose members can evolve
      from any member by single substitutions and that there are "species" defined
      according to the biological species concept. Assuming that the number of genes,
      n, is very large while the proportion of viable genotypes among all possible
      genotypes, p, is very small, we have deduced many qualitative and quantitative
      properties of holey adaptive landscapes which may be related to the patterns of
      speciation. Relationship between p and n determines two qualitatively different
      regimes: subcritical and supercritical. The subcritical regime takes place if p
      is extremely small. In this case, the largest clusters of viable genotypes in the
      genotype space have size of order n and there are many of such size; typical
      members of a cluster are connected by a single ("evolutionary") path; the number
      of different (biological) species in the cluster has order n; the expected number
      of different species in the cluster within k viable substitutions from any its
      member is of order k. The supercritical regime takes place if p is small but not
      extremely small. In this case, there exists a cluster of viable genotypes (a
      "giant" component) that has size of order 2n/n; the giant component comes "near"
      every point of the genotype space; typical members of the giant component are
      connected by many evolutionary paths; the number of different (biological)
      species on the "giant" component has at least order n2; the expected number of
      different species on the "giant" component within k viable substitution from any
      its member is at least of order kn. At the boundary of two regimes all properties
      of adaptive landscapes undergo dramatic changes, a physical analogy of which is a
      phase transition. We have considered the most probable (within the present
      framework) scenario of biological evolution on holey landscapes assuming that it
      starts on a genotype from the largest connected component and proceeds along it
      by mutation and genetic drift. In this scenario, there is no need to cross any
      "adaptive valleys"; reproductive isolation between populations evolves as a side
      effect of accumulating different mutations. The rate of divergence is very fast:
      a few substitutions are sufficient to result in a new biological species. We
      argue that macroevolution and speciation on "rugged" fitness landscapes proceed
      according to the properties of the corresponding holey landscapes.

PMID- 9039401
TI  - The evolution of cooperation in a lattice-structured population.
AB  - The evolution of cooperation among unrelated individuals is studied in a lattice
      structured habitat, where individuals interact locally only with their neighbors.
      The initial population includes Tit-for-Tat (abbreviated as TFT, indicating a
      cooperative strategy) and All Defect (AD, a selfish strategy) distributed
      randomly over the lattice points. Each individual plays the iterated Prisoner's
      Dilemma game with its nearest neighbors, and its total pay-off determines its
      instantaneous mortality. After the death of an individual, the site is replaced
      immediately by a copy of a randomly chosen neighbor. Mathematical analyses based
      on mean-field approximation, pair approximation, and computer simulation are
      applied. Models on one and two-dimensional regular square lattices are examined
      and compared with the complete mixing model. Results are: (1) In the one
      dimensional model, TFT players come to form tight clusters. As the probability of
      iteration w increases, TFTs become more likely to spread. The condition for TFT
      to increase is predicted accurately by pair approximation but not by mean-field
      approximation. (2) If w is sufficiently large, TFT can invade and spread in an AD
      population, which is impossible in the complete mixing model where AD is always
      ESS. This is also confirmed by the invasion probability analysis. (3) The two
      dimensional lattice model behaves somewhat in between the one-dimensional model
      and the complete mixing model. (4) The spatial structure modifies the condition
      for the evolution of cooperation in two different ways: it facilitates the
      evolution of cooperation due to spontaneously formed positive correlation between
      neighbors, but it also inhibits cooperation because of the advantage of being
      spiteful by killing neighbors and then replacing them.

PMID- 9039402
TI  - The irritable bowel syndrome.
AB  - Irritable bowel syndrome is a common disorder varying in severity from trivial to
      incapacitating. The pathophysiology and epidemiology are gradually being
      unravelled and it is now becoming apparent just how poor the quality of life of
      some of these patients can be. It is no longer acceptable practice to diagnose
      the condition and discharge the patient on a high fibre diet, particularly as the
      latter can often make the situation worse. Although hard to treat, worthwhile
      responses can be achieved by careful targeting of therapy to the many different
      facets of the disorder.

PMID- 9039403
TI  - Causes of ischaemic stroke in the young.
AB  - The causes of ischaemic stroke in young adults are many and diverse. Such
      patients usually require more extensive investigations in order to find an
      underlying cause than more elderly patients. It is important that a comprehensive
      search is made since many of the underlying disorders are treatable. Principal
      causes are extracranial arterial dissection, cardioembolism, premature
      atherosclerosis, haematological and immunological disorders and migraine. Drug
      abuse is becoming increasingly important but the risk of stroke in pregnancy
      remains unclear. Isolated angiitis of the central nervous system, heritable
      disorders of connective tissue and other genetically determined disorders
      (mitochondrial cytopathies, CA-DASIL) account for a small proportion of ischaemic
      strokes in the young. Management is probably best undertaken by a physician with
      a specialist interest and, if full investigation fails to elucidate a definite
      cause, the risk of future stoke is low.

PMID- 9039404
TI  - Expanding the role of the nurse in the Accident and Emergency department.
AB  - In response to the increasing demands upon the Accident and Emergency department
      and supported by changes within the scope of professional practice of the
      qualified nurse, Accident and Emergency nurses have expanded their role within
      the multidisciplinary team. The article reviews the development of this expanded
      role for the nurse within the Accident and Emergency team and discusses its
      implications.

PMID- 9039405
TI  - Continuing education for medical professionals: a reflective model.
AB  - The Royal Colleges and their Faculties have moved continuing professional
      development up the agenda of doctors in the UK. The low educational value and
      failure to change professional practice of much continuing medical education has
      led to criticism of its emphasis on formal, didactic teaching and academic
      knowledge. The ubiquitous scientific or technical bias in medical education makes
      questionable assumptions about the nature of professional knowledge, how
      professionals learn, and the linkage of theory and practice in professional work.
      Given its narrow conception of professional knowledge, it is hardly surprising
      that the effectiveness of continuing medical education has proven difficult to
      evaluate. These points of criticism suggest that a more systematic and coherent
      approach to continuing education is required. The adoption of the concept of
      continuing professional development, which draws on learning by reflective
      practice, marks an important step in this direction. Continuing professional
      development emphasises self-directed learning, professional self-awareness,
      learning developed in context, multidisciplinary and multilevel collaboration,
      the learning needs of individuals and their organisations, and an inquiry-based
      concept of professionalism. It also involves a widening of accountability to
      patients, the community, managers and policymakers, and a form of evaluation
      which is internal, participatory and collaborative rather than external and
      scientific in character.

PMID- 9039407
TI  - Consultants' study leave--value for money?
AB  - The consultants in a single large acute hospital trust were given a personal
      allocation of 500.00 pounds for study leave and asked to supply reports on the
      purpose and value of that leave. The majority of consultants (82%) took leave
      during the 12-month period at an average cost of 182.80 pounds for each episode.
      Most was regarded of value and the majority was shared with other members of
      staff.

PMID- 9039406
TI  - Wernicke-Korsakoff syndrome.
AB  - Alcohol abuse is one of the most serious problems in public health and the
      Wernicke-Korsakoff syndrome is one of the gravest consequences of alcoholism. The
      pathology is often undiagnosed in its less evident presentations, therefore an
      accurate diagnostic approach is a critical step in treatment planning. Treatment
      is based on restoration of thiamine, although this is insufficient to prevent the
      psychological decline of a great number of patients. The cognitive impact of the
      pathology is derived from the interaction of alcoholic neurotoxicity, thiamine
      deficiency and personal susceptibility. In this article, the literature
      concerning Wernicke-Korsakoff syndrome is reviewed.

PMID- 9039408
TI  - Warwickshire consultants' 'training the trainers' course.
AB  - To train junior hospital doctors more quickly and effectively as envisaged by the
      Calman reforms, consultants will need to develop their adult education skills.
      This paper describes a course set up and attended by a mixed group of
      Warwickshire consultants to improve their understanding of these skills. The
      course organisation and content is described and the 'learner-centred education'
      model, educational supervision techniques, giving feedback on performance, goal
      setting, learning contracts and other topics covered are explained. A 12-month
      interval questionnaire evaluation by attendants shows that the principles taught
      in the course were being widely applied a year later. Thus, at a modest cost,
      consultants can receive a valuable basic training in adult education.

PMID- 9039409
TI  - A patient with Graves' disease, thrombocytopenia and chronic hepatitis B.
AB  - A 22-year-old Chinese man, a HBsAg carrier, presented with relapse of thyrotoxic
      Graves' disease complicated by thrombocytopenia and hepatitis. Platelet count and
      liver enzymes gradually improved following successful treatment of the
      thyrotoxicosis with radioactive iodine. Possible pathogenetic links and
      therapeutic implications are discussed.

PMID- 9039410
TI  - Typhoid fever with severe pancytopenia.
AB  - A patient suffering from typhoid fever with severe pancytopenia is presented.
      Bone marrow examination revealed extensive haemophagocytosis which possibly
      contributed to the pancytopenia.

PMID- 9039411
TI  - False aneurysm with median nerve palsy after iatrogenic brachial artery puncture.
AB  - We report on a case in which a patient on oral anticoagulation for her aortic
      valve replacement, with an International Normalised Ratio of 2.13, developed a
      false aneurysm of the brachial artery after a routine arterial puncture, despite
      direct pressure to the aspiration site. The false aneurysm was complicated by the
      development of median nerve palsy.

PMID- 9039412
TI  - Malignant change in a chronic skin lesion induced by an intravenous cannula.
AB  - A cutaneous wound subjected to continuous irritation has an increased potential
      for malignant degeneration. The types of trauma that may give rise to the initial
      injury are diverse and have been well documented. We report a case of one such
      lesion in a 65-year-old man who had a persistent right forearm wound for over
      three years. The wound arose from the site of venous cannula puncture. Malignant
      transformation occurred in a manner comparable to that seen in other chronic
      lesions (Marjolin's ulcer).

PMID- 9039413
TI  - Carcinoma of the sigmoid colon presenting as a scrotal swelling.
AB  - A case of adenocarcinoma of the sigmoid colon, presenting as a testicular mass,
      is described. At sigmoid colectomy widespread metastases were found and only
      palliative care could be offered thereafter. The incidence and age of such a
      presentation and manner of spread of the occult primary are discussed.

PMID- 9039414
TI  - A painful knee in an immunocompromised patient.

PMID- 9039415
TI  - Calcification in a gastric neoplasm.

PMID- 9039416
TI  - Hyponatraemia at a rave.

PMID- 9039417
TI  - Ptosis in an elderly man.

PMID- 9039418
TI  - Hypernatraemia.

PMID- 9039419
TI  - Hypercalcaemia.

PMID- 9039420
TI  - Thyroid storm presenting as status epilepticus and stroke.

PMID- 9039421
TI  - Endocarditis caused by Lactobacillus.

PMID- 9039422
TI  - Emergency blood test guidelines.

PMID- 9039423
TI  - Cardiopulmonary resuscitation.

PMID- 9039424
TI  - Octreotide therapy for diarrhoea.

PMID- 9039426
TI  - The lipids in human milk.
AB  - The summary will be limited to the areas that should be intensively investigated.
      The first is: determination of fatty acid profiles using modern methods on a
      world wide basis. We have no more than five or six papers in which my criterion
      was applied, one from Canada and the remainder from Europe with some data from
      Africa. Obviously, milk cannot be used as the gold standard on this meager data
      base. The second area is analysis of TG structure. These analyses are difficult,
      but structure is one of the factors controlling digestion. Data on the effects of
      maternal diet on structure would be useful. The third area is the role of primary
      or derived milk lipids as microbicidal agents. The fourth area is examination of
      globule parameters, i.e. number, size, volume, surface, and how they are affected
      by diet. There are many others which may interest the reader.

PMID- 9039425
TI  - Betaine ether-linked glycerolipids: chemistry and biology.

PMID- 9039427
TI  - The Hybaid Lecture. Microcollinearity and segmental duplication in the evolution
      of grass nuclear genomes.
AB  - Recent studies have shown that grass genomes have very similar gene compositions
      and regions of conserved gene order, as exemplified by collinear genetic maps of
      DNA markers. We have begun the detailed study of sequence organization in large
      (100-500 kb) segments of the nuclear genomes of maize, sorghum and rice. Our
      results indicate collinearity of genes in the regions homoeologous to the maize
      adh1 and sh2-a1 genes. Comparable genes were found to be physically closer to
      each other in grasses with small genomes (rice and sorghum) than they are in
      maize. In several instances, we have found evidence of tandem and 'distantly
      tandem' duplications of segments containing maize and sorghum genes. These
      duplications complicate characterizations of microcollinearity and could also
      interfere with some map-based approaches to gene isolation.

PMID- 9039428
TI  - Sequencing and mapping the Arabidopsis genome: a weed model for real crops.
AB  - Arabidopsis is a crucifer weed with a small genome of about 120 Mbp which has
      been chosen as a model species for plant molecular genetics. Four years ago, a
      consortium of nine French laboratories, including ours, initiated a project aimed
      at mapping the transcribed regions of the genome. The strategy employed was to
      systematically and randomly sequence cDNA clones isolated from libraries made
      from different tissues and organs of plants grown under various physiological
      conditions. The consortium released about 7,000 expressed sequenced tags (ESTs)
      in the dbEST database corresponding to approximately 3,500 unique genes. In the
      next phase of the programme, a YAC library with average inserts of 500 kbp has
      been prepared. We have now started to use the EST information to map the cDNA
      clones on these YACs. The most recent aspect of Arabidopsis sequencing is the
      ESSA (European Scientists Sequencing Arabidopsis) project, in which the aim is to
      describe 2.5 Mbp by the end of 1996. Genomic sequencing has revealed a very high
      gene density. Comparison of present genomic sequencing results with the EST data
      suggests that up to half of the genes might already be tagged with an EST. In
      collaboration with Carlos Quiros' group in Davis we have also analysed the
      conservation of a 30 kbp locus (Em 1, a late embryogenesis abundant protein gene)
      on chromosome 3 between Arabidopsis and several Brassica species. Progress on
      these various aspects will be reviewed. We shall also present some sequence
      comparisons between Arabidopsis and rice ESTs. These results suggest that it
      should be possible in the very near future to map a pool of common genes onto
      many different plant genomes. This should provide a common framework to integrate
      maps from different species and facilitate mapbased cloning of genes of
      agronomical importance.

PMID- 9039429
TI  - Rice cDNAs as a model for expressed genes of plants.
AB  - Large-scale rice cDNA analysis has produced a huge amount of nucleotide sequence
      information for expressed genes in rice. The genes of cDNA clones putatively
      identified by similarity search were originally found in many different
      organisms. However, genes identified at a higher confidence level were found in
      plants, especially in monocots. This means the sequence information produced in
      random cloning of rice cDNA is useful for the study of other Gramineae. Further,
      assigned gene names of cDNAs mapped on linkage group 6 were grouped by their
      original species. The functions of gene products for 51% of mapped cDNAs were
      assigned and 67% of them were known in plants. The map information obtained by
      linking the position of a cDNA locus and its assigned gene function is
      indispensable for elucidating collinearity of genes among plant genomes.

PMID- 9039430
TI  - Comparative analysis of plant genome architecture.
AB  - Many genes are similar in most plants and it is clear that the ordering of genes
      is highly conserved across wide taxonomic groupings. Repetitive DNA, consisting
      of sequence motifs between 2 and 10,000 base pairs long, repeated many hundreds
      or thousands of times in the genome, represents the majority of most plant
      genomes and defines some of the differences between species. Some sequences are
      highly conserved in many species, while other sequences show species or even
      chromosome specificity. Different types of sequences have markedly contrasting
      genomic distributions; even among tandem repeats, some are sub-terminal, some
      paracentromeric and others intercalary. The reasons for these different
      distributions are largely unknown, and mechanisms of homogenization, dispersion
      and amplifications are the subject of much speculation. Aspects of plant genome
      architecture-the organization of repetitive and single-copy DNA sequences along
      the chromosomes, and the positioning of those sequences within the nucleus at
      interphase-have important consequences for plant genetics. Models of large scale
      genome organization may be useful in learning the function of different
      components of the genome, in evolutionary studies and in plant breeding.

PMID- 9039431
TI  - Physical and topographical mapping among Triticeae chromosomes.
AB  - Three principal approaches have been used in our laboratory to analyze Triticeae
      genomes. (i) Synteny analysis: synteny among different Gramineae genomes was
      studied employing the elegant system of the Agropyron chromosome-induced deletion
      lines of wheat. Deletion mapping, predominantly of the homoeologous group 7
      chromosomes, has led to the construction of a high density physical consensus map
      of wheat. The integration of wheat, barley and oat RFLP markers proves the
      colinearity between the wheat A-, B- and D-genomes, the H-genome of barley, and
      the E-genome of Agropyron. (ii) Light microscopic in situ techniques: the recent
      improvement of a drop technique for plant protoplasts was crucial for the
      sensitivity enhancement of fluorescence in situ hybridization (FISH), the
      efficient preparation of plant chromosomes for high resolution scanning electron
      microscopy, mapping of low-copy sequences, and comparative in situ hybridization.
      A tandemly amplified repetitive sequence element from microdissected barley
      chromosomes has enabled the karyotyping of Gramineae genomes in a single step. We
      have isolated and characterized members of this element family from other
      Triticeae species using PCR. The significant interspecific sequence differences
      were useful to identify single plant genomes, chromosomes and chromosome segments
      via post-hybridization washes under different stringency conditions. These
      sequences are also useful for simultaneous double or triple hybridization
      experiments in an attempt to localize new sequences on specific chromosomes or
      chromosome segments. The physical mapping of the Sec-1 locus has been refined on
      the satellite of chromosome 1R of rye, and the syntenic locus on barley
      chromosome 1H was identified. (iii) Physical mapping of rDNA sequences by high
      resolution electron microscopy: a method was developed for in situ hybridization
      and signal detection using high resolution field emission scanning electron
      microscopy and a backscattered electron detector. Colloidal gold particles were
      localized on chromosome structures resembling the 30 nm fibre. An rDNA probe was
      located in the secondary constriction and the highly compact adjacent regions of
      barley chromosomes.

PMID- 9039432
TI  - Comparative genetic and QTL mapping in sorghum and maize.
AB  - DNA markers and genetic maps will be important tools for direct investigations of
      several facets of crop improvement and will provide vital links between plant
      breeding and basic plant biology. The markers and maps will become more important
      for increased crop production because plant genetics will be required to extend
      or replace extant management practices such as chemical fertilizers, pesticides,
      and irrigation (Lee, 1995). Despite the importance of the sorghum crop,
      comprehensive genetic characterization has been limited. Therefore, the primary
      goal of this research program was to develop basic genetic tools to facilitate
      research in the genetics and breeding of sorghum. The first phase of this project
      consisted of constructing a genetic map based on restriction fragment length
      polymorphisms (RFLPs). The ISU sorghum map was created through linkage analysis
      of 78 F2 plants of an intraspecific cross between inbred CK60 and accession
      P1229828 (Pereira et al., 1994). The map consists of 201 loci distributed among
      10 linkage groups covering 1,299 cM. Comparison of sorghum and maize RFLP maps on
      the basis of common sets of DNA probes revealed a high degree of conservation as
      reflected by homology, copy number, and collinearity. Examples of conserved and
      rearranged locus orders were observed. The same sorghum population was used to
      map genetic factors (mutants and QTL) for several traits including vegetative and
      reproductive morphology, maturity, insect, and disease resistance. This
      presentation will emphasize analysis of genetic factors affecting plant height,
      an important character for sorghum adaptation in temperate latitudes for grain
      production. Four QTL for plant height were identified in a sample of 152 F2
      plants (Pereira and Lee, 1995) whereas 6 QTL were detected among their F3
      progeny. These observations and assessments of other traits at 4 QTL common to F2
      plants and their F3 progeny indicate some of these regions correspond to loci
      (dw) previously identified on the basis of alleles with highly qualitative
      effects. Four of the six sorghum plant height QTL seem to be orthologous to plant
      height QTL in maize. Other possible instances of orthologous QTL included regions
      for maturity and tillering. These observations suggest that the conservation of
      the maize and sorghum genomes encompasses sequence homology, collinearity, and
      function. The genetic information and technology developed on the basis of DNA
      markers could be used in several facets of breeding, genetics, and other basic
      biological investigations. In addition, DNA markers have been used to survey
      large collections of elite sorghum germ plasm to determine the degree of genetic
      relationships and genetic diversity (Ahnert et al., 1996). RFLP data seem to
      portray genetic relationships more accurately than the methods based exclusively
      on the coancestry coefficient. This information provides the basis for more
      accurate perceptions of genetic relationships and diversity.

PMID- 9039433
TI  - QTL for insect resistance and drought tolerance in tropical maize: prospects for
      marker assisted selection.
AB  - Insects and drought cause severe losses in the production of maize in many
      developing countries. Conventional breeding efforts to enhance the level of
      resistance to a number of insect pests and tolerance to drought have been
      successful, although only through large efforts of many breeders and over a large
      period of time. Continued improvements will only be possible through substantial
      investment of resources. Recently, success in identifying quantitative trait loci
      (QTL) in several plant species using various molecular marker systems offers
      alternative methods for accelerating conventional breeding programs. As the first
      step towards using molecular markers in CIMMYT's maize breeding program,
      restriction fragment length polymorphisms (RFLPs) have been used to understand
      the genetic basis of resistance to two corn borer species, southwestern corn
      borer and sugarcane borer, and to one major component of drought tolerance,
      anthesis-silking interval. A number of QTL with effects large enough to be
      regarded as significant in breeding were detected for each of these traits and
      many of them presented stable effects over environments. While variability in the
      number and location of QTL has been found when compared across populations,
      several loci were found to be quite consistent. Simple calculations can be made
      which estimate that the total genetic potential in maize for these traits is
      high. It is argued that to ultimately access and manipulate this potential, the
      use of linked molecular markers as indirect selectable markers is both feasible
      and necessary.

PMID- 9039434
TI  - Genetic recombinational and physical linkage analyses on slash pine.
AB  - Slash pine is native to the southeastern USA, but is commercially valuable world
      wide as a timber-, fiber- and resin-producing species. Breeding objectives
      emphasize selection for fusiform rust disease resistance. Identification of
      markers linked to genetic factors conditioning specificity should expand our
      knowledge of disease development. Towards this end, random amplified polymorphic
      DNA (RAPD) markers were identified and mapped in a tree hypothesized to be
      homozygous dominant for resistance at one locus and homozygous recessive at
      another. Because the DNA prepared for analysis was from haploid maternally
      inherited, megagametophyte tissue of seeds, RAPD markers were observed as either
      present or absent. The analysis revealed 13 linkage groups of three or more loci,
      ranging in size from 28 to 68 cM, and nine linked pairs. The 22 groups and pairs
      included 73 RAPD markers and covered a genetic map distance of approximately 782
      cM. Genome size estimates, based on linkage data, range from 2,880 to 3,360 cM,
      and equal 6.0-6.9 x 10(6) bp/cM (physical size > 20,000 Mbp). Using a 30 cM map
      scale and including unlinked markers, ends of linkage groups, and linked pairs,
      the RAPD markers account for approximately 2,160 cM or 64-75% of the genome.
      Mapping 80 additional RAPD markers placed 131 loci total in 20 linkage groups of
      three or more loci, nearly doubling the coverage in the groups to a genetic map
      distance of approximately 1,347 cM. Two other slash pine trees also have been
      RAPD mapped. DNA-DNA in situ hybridization and cytochemical staining are being
      used to integrate the genetic recombinational maps. A karyotype and ideogram have
      been prepared for slash pine (2n = 2x = 24); metaphase chromosome preparations
      show 11 pairs of long metacentric chromosomes and one shorter pair of
      submetacentric chromosomes. Patterns of fluorescence in situ hybridization to
      genes for the large and small rRNA subunits and fluorochrome banding patterns
      using the GC-base-specific chromomycin A3 (CMA) and AT-base-specific 4',6
      diamidino-2-phenylindole (DAPI) allowed all twelve pairs of chromosomes to be
      identified and a standard karyotype established. A family of sequences associated
      with (TTTAGGG)n related repeats has been identified in slash pine using a labeled
      synthetic oligonucleotide probe. Fluorescence in situ hybridization shows a weak
      signal at telomeres and significantly stronger intensity at non-telomeric sites.
      The most common non-telomeric location was in the pericentric regions of
      chromosomes; interstitial sites of hybridization were relatively common.
      Microsatellite DNAs, an abundant retrotransposon-like element, and total genomic
      in situ hybridization and species and chromosome specific DNAs are being
      evaluated for analyses of interspecific hybrids and chromosome evolution between
      related species. Interest in low and single copy sequences is increasing.

PMID- 9039435
TI  - The nucleotype, the natural karyotype and the ancestral genome.
AB  - New knowledge of synteny and collinearity promises to unify genetics and to
      affect our perception of higher order genome structure. This exciting new
      synthetic approach emphasizes genomic similarities rather than diversity. Two
      other aspects of genomic form and organisation, offering potentially unifying
      concepts in genome studies are: the nucleotype, and the natural karyotype. Genome
      size varies greatly between eukaryotes, and shows many strikingly precise
      correlations with phenotypic characters, independent of information encoded in
      DNA. Such nucleotypic correlations, based on biophysical absolutes, apply to all
      species, irrespective of genome size or chromosome number, and set limits on the
      range of phenotypes which can be expressed by genic control. Thus, knowledge of
      nucleotypic effects has considerable predictive value which can help to unify our
      understanding of genomes. Other studies of reconstructed nuclei have shown that:
      (1) the basic haploid genome exists as a real structural unit in nuclear
      architecture; while (2) the mean spatial arrangement of its heterologues also
      exists as a natural karyotype which is predictable using a simple model. Recently
      reported conceptual alignments of the maize genomes, which reflect the
      circularized ancestral grass genome, show interesting similarities with the
      orders of centromeres in their natural karyotypes predicted by the Bennett model.
      The basis of this phenomenon (if repeated in other species), and of selection
      which retains the ancestral genome form despite changes in basic chromosome
      number, may need to be explained. Perhaps the overall 3-D structure of the genome
      has some critical functional significance, essential for development. If so, a
      knowledge of this common structure would further unify our understanding of
      genomes and their evolution.

PMID- 9039436
TI  - Unifying plant molecular data and plants.
AB  - Located at a botanical department at an Agricultural University, our taxonomical
      and genetic research is mainly directed towards cultivated plants and their wild
      relatives. The investigations are usually under a common heading 'experimental
      taxonomy', and include basic systematics, cytogenetics, biodiversity, population
      dynamics, conservation and evolutionary questions correlating the wild species
      and the cultivated forms. Our point of initiation is the plants and
      questions/problems raised regarding these plants. Our way of approaching the
      problems is usually by applying different sets of data and testing them.
      Experimental taxonomy covers classical cytogenetics (chromosome counting and
      karyotyping) as well as molecular cytogenetic methods (RAPD, RFLP, in situ
      hybridization), and includes also chemical data on isoenzymes and anthocyanins.
      We have had good collaborations with other laboratories and found their expertise
      on the plants in question very helpful. The aim is always to unify various data
      on the same set of problems, in order to get a more complete understanding of the
      plants. At present the department is working on several, quite different plant
      genera, comprising herbs, aquatic plants, and trees. The methods vary, depending
      on the plants and the problems in question. Some of the current investigations
      concern the horticultural genera Lilium and Crocus, in which the main point of
      interest is the study of chromosome evolution using fluorescence in situ
      hybridization; preliminary investigations into the composition of anthocyanins in
      Crocus look very promising. In the tropical starch tuber crop Pachyrhizus
      (Fabaceae), molecular analyses of relationships between existing cultivars,
      landraces and wild material have been carried out. A genus which we, in
      cooperation with a number of other laboratories, have been working with for many
      years is Hordeum (Poaceae) with one cultivated species (barley) and 31 wild
      species. Here the main areas of investigation have been field studies and
      collecting, followed by a taxonomical treatment, hybridization experiments,
      cytogenetic analysis and isoenzyme studies. Within the field of forestry, we have
      used population genetics as a tool in the management of natural and domesticated
      populations and for conservation of genetic diversity. We have also ventured into
      the identification and use of DNA markers that are suited for genome mapping in
      Picea abies (Norway Spruce).

PMID- 9039437
TI  - Molecular characterization of heterochromatic regions around the Tm-2 locus in
      chromosome 9 of tomato.
AB  - The gene Tm-2 (tomato mosaic virus (ToMV) resistant), which is tightly linked to
      a morphological marker gene nv (netted virescent), resides in a heterochromatic
      region near the centromere of chromosome 9 in tomato. Tm-2 and Tm-2a are known to
      be allelic, and exhibit similar phenotypes to each other, but can be
      differentiated by their response to different ToMV strains. An inoculation
      experiment demonstrated that Tm-2 helped a mutant strain of ToMV to infect a
      heterozygous tomato (Tm-2/Tm-2a). Aiming at investigating the structures of DNA
      around these active genes and their influence on gene activities, we attempted to
      identify and characterize random amplified polymorphic DNA (RAPD) markers linked
      to these genes using nearly isogenic lines (NILs) of tomato. Genetic analysis
      using 13 RAPD markers linked to the Tm-2 locus and cytological analysis by
      fluorescence in situ hybridization (FISH) demonstrated that the lines resistant
      to ToMV had a large block derived from a chromosome of Lycopersicon peruvianum.
      Among these markers, we estimated that two, OPE16(900) and OPN31(1000), are
      nearest to the Tm-2 locus. Out of the 13 markers six, distributed within about
      0.7 centi-Morgan (cM), were cloned and sequenced to be converted to sequence
      characterized amplified region (SCAR) markers. Of these, four were successfully
      converted to SCAR markers. The six clones were also used as probes for Southern
      hybridization of genomic DNA from NILs to characterize structures around the Tm-2
      locus. One clone was estimated to be derived from a sequence that was present in
      one copy. The other five clones appeared to be derived from different kinds of
      moderately or highly repetitive sequences.

PMID- 9039438
TI  - The physical organization of Triticeae chromosomes.
AB  - Molecular cytogenetics combines molecular information of DNA sequences with their
      chromosomal organization. Genomic in situ hybridization using total genomic DNA
      as a probe is proving particularly useful to paint chromosomes originating from
      different genomes in hybrids, alloploid species and alien plant breeding lines.
      Both the numbers and morphologies of alien chromosomes or chromosome segments can
      be detected at metaphase and interphase. The method also gives considerable
      information about species relationships and the distribution of common or diverse
      DNA sequences between closely related species. Painted chromosomes can be
      followed through all stages of the cell cycle of somatic and meiotic division,
      providing new information about chromosome behaviour and pairing at meiosis. In
      situ hybridization with defined probes enables the physical location of
      particular DNA sequences to be examined along chromosomes and the analysis of the
      long range organization of specific chromosome regions. The generation of an
      integrated genetical, physical and functional map will be useful for the
      understanding of the organization and structure of the cereal genome.

PMID- 9039439
TI  - Why sequence the genome of Mycobacterium tuberculosis?
AB  - Radical measures are required to prevent the grim predictions of the World Health
      Organisation for the deterioration of the global tuberculosis epidemic in the
      next century from becoming reality. Study of the nerve centre of the tubercle
      bacillus, its genome, by means of systematic deoxyribonucleic acid sequence
      analysis will provide a wealth of information about Mycobacterium tuberculosis
      that will undoubtedly fuel the next generation of research. In the coming year,
      this highly cost-effective approach will deliver an unprecedented amount of
      knowledge to catalyse the development of new, more efficient diagnostic tools and
      therapeutic interventions to detect, control and, ultimately, eliminate
      tuberculosis.

PMID- 9039440
TI  - Combined effect of pyrazinamide and ofloxacin within the human macrophage.
AB  - SETTING: Recent reports of outbreaks of multidrug resistant tuberculosis have
      raised questions as to the most appropriate therapeutic response for those
      exposed to such organisms. A recent Centers for Disease Control National Action
      Plan suggests the combination of pyrazinamide (PZA) and a quinolone as a
      potential preventive therapy regimen. OBJECTIVE: Prior studies in the ex-vivo
      human macrophage model have shown PZA to have only a bacteriostatic effect and,
      in addition, to diminish the bactericidal effect of rifampin. This study was
      designed to quantify the intramacrophage antimycobacterial effect of PZA when
      combined with a quinolone (ofloxacin). DESIGN: Forty micrograms/ml of PZA was
      combined with varying concentrations of ofloxacin and administered to human
      macrophages infected with virulent tubercle bacilli; drug sequencing was also
      studied. RESULTS: A clinically achievable level of PZA enhances the
      antimycobacterial effect of low, non-bactericidal levels of ofloxacin and does
      not impede the bactericidal effect of a higher clinically effective level of
      ofloxacin. Unlike the combination of PZA and rifampin, these interactive effects
      are not affected by the sequence of drug administration. CONCLUSIONS: Findings
      support the use of these agents as a potentially effective preventive therapy
      combination for individuals exposed to multidrug resistant tuberculous organisms.

PMID- 9039441
TI  - Burden of Mycobacterium tuberculosis in sputum samples can be reliably determined
      using a quantitative, non-radioactive polymerase chain reaction assay.
AB  - OBJECTIVE: To develop a rapid assay for quantitation of Mycobacterium
      tuberculosis in sputum samples using the competitive polymerase chain reaction
      (PCR) and a colorimetric microtiter well detection format. DESIGN: The assay
      relies on the co-amplification of a 419 base pair (bp) pab fragment of M.
      tuberculosis together with a target template (pab/tet) made by splicing a
      fragment of tet excised from pbr322 between the 5' and 3' ends of the pab
      fragment to create a 380 bp hybrid template amplified with the same primers but
      readily distinguishable using probes specific for either pab or tet. RESULTS: We
      demonstrate a good correlation between the results obtained using this assay and
      the results of quantitative culture. CONCLUSION: This assay provides quantitative
      information regarding M. tuberculosis burden in samples containing between 10(3)
      and 10(8) colony forming units/milliliter (CFU/ml).

PMID- 9039442
TI  - Anti-IgG autoantibodies and possible immune regulatory mechanisms in patients
      with pulmonary tuberculosis.
AB  - SETTING: Anti-Ig antibodies are known to have important clinical and biological
      implications. OBJECTIVES: To determine naturally occurring anti-F(ab')2 gamma and
      anti-Fc gamma antibodies in patients with pulmonary tuberculosis (PTB) in
      relation to various clinical manifestations and human leukocyte antigen (HLA).
      DESIGN: Antibodies to F(ab')2 and Fc portions of IgG were detected in the sera of
      normal healthy individuals (n = 41), patients with pulmonary tuberculosis (n =
      50) and their household family contacts (n = 20) using an enzyme immuno assay
      (EIA) system. RESULTS: As compared to controls (0.110 +/- 0.01 optical density
      [OD]), the levels of anti-F(ab')2 gamma were significantly increased in PTB
      patients (0.998 +/- 0.08 OD, P < 0.0001) and in their contacts (0.486 +/- 0.04
      OD, P < 0.001) suggesting that the occurrence of these autoantibodies is related
      to infection/exposure to Mycobacterium tuberculosis. Anti-F(ab')2 gamma
      antibodies were significantly increased in both sputum positive and negative
      patients (P < 0.0001) and no deviation was observed between these two groups. The
      levels of these antibodies were positively correlated with disease severity
      assessed by chest X-ray. The drug failure patients had higher activity of anti
      F(ab')2 gamma than drug responders and no impact of anti-tuberculosis
      chemotherapy was observed. A statistically significant increase of anti-F(ab')2
      gamma levels (1.25 +/- 0.21 OD) was observed in HLA-DR2 positive patients as
      compared to the DR2 negative groups (1.02 +/- 0.09 OD), P < 0.01. No deviation
      was observed in the levels of anti-Fc gamma levels between controls and any group
      of PTB patients. CONCLUSION: The present data suggests that the elevated levels
      of anti-F(ab')2 gamma antibodies in PTB patients represent an anti-idiotypic
      antibody response to anti-M. tuberculosis antibody caused by an immune imbalance
      following M. tuberculosis infection.

PMID- 9039443
TI  - Serodiagnosis of tuberculosis: detection of mycobacterial antibodies and
      antigens.
AB  - SETTING: The diagnosis of tuberculosis is based primarily on identification of
      mycobacteria and on clinical evidence. Recently, serological studies have been
      widely used experimentally as a diagnostic approach. OBJECTIVE: The aim of our
      study was to optimize serodiagnosis of tuberculosis by detecting mycobacterial
      antigens and antibodies in sera from patients with lung tuberculosis, non-related
      diseases and healthy controls. DESIGN: Mycobacterium tuberculosis H37Rv was
      disintegrated by pressure. Cell walls were extracted with 3 M KCL and were
      subjected to gel filtration in Toyopearl gel. Immune sera were prepared by
      immunization of rabbits with cell wall material. Anti H37Rv antibodies were
      purified by affinity chromatography. The reagents obtained were used to detect
      serum antibodies and antigens (following immune complex dissociation) using
      ELISA. RESULTS: Using fraction 6 of cell wall extract, antibodies were detected
      in 72.2% of TB patients; there were no positive reactions in control subjects. By
      use of affinity-purified antibodies, antigens were detected in 77.1% of TB
      patients, 10% of patients with unrelated diseases and 6.7% of healthy controls.
      CONCLUSION: Effective serodiagnosis of tuberculosis can be achieved only by
      combining detection of both circulating antibodies and antigens using highly
      specific purified reagents and immune complex-dissociated sera.

PMID- 9039444
TI  - Immune activation, allergic drug toxicity and mortality in HIV-positive
      tuberculosis.
AB  - SETTING: Tuberculosis Treatment Center, Kampala, Uganda. OBJECTIVE: HIV-1 affects
      outcome in pulmonary tuberculosis (TB). Immune mechanisms triggered by
      Mycobacterium tuberculosis may lead to increased HIV expression and accelerated
      disease progression. This study was conducted to correlate serum levels of
      markers of immune activation with mortality and drug toxicity in HIV + TB.
      DESIGN: Substudy of a randomized clinical trial of streptomycin-thiacetazone
      isoniazid (STH) vs. rifampin-isoniazid-pyrazinamide (RHZ) in HIV + TB. RESULTS:
      Neopterin > or = 14 ng/ml, TNF-alpha receptors > or = 6.5 ng/ml, and negative
      skin test were independently associated with increased mortality (P < 0.01).
      Among STH-treated subjects, dermatologic toxicity and mortality were respectively
      13- and 6.3-fold more likely to occur in subjects with elevated neopterin (P <
      0.05), although these two adverse events occurred independently. Activation
      markers increased from baseline after 2 months of therapy with the less rapidly
      bactericidal STH regimen, whereas they declined in those treated with RHZ,
      suggesting a relationship with continued mycobacterial replication. CONCLUSIONS:
      Immune activation in HIV + TB is associated with shortened survival and increased
      risk of drug toxicity. HIV + TB patients with elevated serum neopterin should be
      treated with a rapidly-bactericidal drug regimen which does not include
      thiacetazone.

PMID- 9039445
TI  - Tuberculosis among foreign-born persons in Los Angeles County, 1992-1994.
AB  - OBJECTIVES: To describe the epidemiology of foreign-born tuberculosis (TB) cases
      in Los Angeles County and to evaluate current TB screening and follow-up of
      immigrants and refugees (I&R) to the USA. DESIGN: Retrospective analysis of the
      Los Angeles County TB registry between October 1992 and December 1994. We matched
      all cases who entered the USA during fiscal year 1993 (FY93) with a database from
      the tracking system of I&R with suspected TB. RESULTS: Foreign-born persons
      accounted for 64% of all reported TB cases. Half were born in Mexico or Central
      America. Standardized incidence rates were 3-5 times higher than those of US-born
      persons for Mexicans and Central Americans, 6-7 times higher for North-east
      Asians, and 10-15 times higher for South-east Asians. Among foreign-born cases
      who arrived during FY93, 5% of the Mexicans and Central Americans, 48% of the
      North-east Asians and 67% of the South-east Asians were registered by the
      tracking system. CONCLUSION: Mexicans and Central Americans accounted for the
      majority of cases but had a lower incidence of TB than Asians. The current
      screening procedures identify a large proportion of cases among recently arrived
      South-east Asians, but contribute little to the control of TB among Mexicans and
      Central Americans.

PMID- 9039447
TI  - Passive smoking and risk of pulmonary tuberculosis in children immediately
      following infection. A case-control study.
AB  - SETTING: Passive smoking-related respiratory disorders in children. OBJECTIVES:
      To assess the effect of passive smoking on the development of active pulmonary
      tuberculosis (PTB) in children immediately following infection by Mycobacterium
      tuberculosis within the family. DESIGN: An unmatched case-control study in which
      93 contacts who became cases (active PTB diagnosed) and 95 contacts who did not
      became cases (tuberculin-positive children without evidence of active disease)
      were included. All were household contacts of a new case of pulmonary bacillary
      tuberculosis. Smoking habits were investigated by a questionnaire. Urinary
      cotinine was analysed. Odds Ratio (OR) was adjusted for age and socio-economic
      status using multiple logistic regression analysis. RESULTS: Passive smoking was
      a risk factor for PTB (OR: 5.29; 95% confidence interval (CI): 2.33-12.82; P <
      0.00005). The adjusted OR was 5.39 (95% CI: 2.44-11.91; P < 0.00001). The risk
      increased when contacts were passive smokers both at home and outside the home
      within the family (OR: 6.35; 95% CI: 3.20, 12.72; P < 0.00001). Contacts 0-4 and
      5-9 years old showed a significantly higher risk than those aged > or = 10. There
      was a dose-response relationship between the risk of developing active PTB
      immediately following infection and the number of cigarettes smoked daily by the
      household adults (P < 0.001). Mean (SD) urinary continine detectable
      concentrations (ng/ml) were different between disease contacts (119.46 [68.61])
      and non diseased contacts (91.87 [73.10]). The difference was statistically
      significant (P < 0.001). CONCLUSIONS: Passive exposure to tobacco smoke in
      children was associated with an increased risk of developing pulmonary
      tuberculosis immediately following infection. This is an association of great
      concern requiring health education programmes and antitobacco medical advice.

PMID- 9039446
TI  - Nosocomial transmission of tuberculosis among mentally-handicapped patients in a
      long-term care facility.
AB  - SETTING: A long-term care facility at Saint-Brieuc hospital, France. OBJECTIVE:
      To investigate a nosocomial outbreak of culture-positive pulmonary tuberculosis
      in 6 (40%) of 15 mentally handicapped HIV-seronegative patients. DESIGN: The
      factors contributing to the outbreak were analyzed and the restriction fragment
      length polymorphism (RFLP) patterns of the six Mycobacterium tuberculosis strains
      were compared. RESULTS: RFLP analysis of the six strains demonstrated an
      identical banding pattern, thus confirming the spread of a unique strain. A
      prolonged period of contagiousness due to a delay in diagnosis of the source
      patient, as well as crowded living conditions in the facility, probably
      contributed to the outbreak. Surveillance of residents and staff in contact with
      the source patient resulted in the detection of five secondary cases. Because
      effective isolation of mentally handicapped patients in the long-term care
      facility turned out to be difficult, the six case-patients were transferred to
      the pneumology department, thus limiting the spread of tuberculosis to other
      residents and staff. CONCLUSIONS: The present outbreak emphasizes the
      difficulties of implementing control measures for preventing the nosocomial
      transmission of tuberculosis in long-term care facilities for mentally
      handicapped patients.

PMID- 9039448
TI  - Tuberculosis due to Mycobacterium bovis in humans in the south-west region of
      Ireland: is there a relationship with infection prevalence in cattle?
AB  - OBJECTIVE: To compare the incidence of tuberculosis due to Mycobacterium bovis in
      humans to the prevalence of M. bovis infection in cattle in south-west Ireland
      and discuss possible links between them. SETTING: In the south-west region of
      Ireland, a mixed urban and rural community (pop. 536,000), there is a residuum of
      human tuberculosis caused by M. bovis. METHODS: A retrospective analysis of the
      incidence of culture-positive M. bovis disease in humans in south-west Ireland
      from 1983 to 1994 and of the results of tuberculin testing in cattle from 1978 to
      1994 for the same region. RESULTS: One to five cases of human tuberculosis due to
      M. bovis were recorded per year while the overall prevalence of bovine infection
      fell gradually during the period of study from 467 tuberculin-positive animals
      per 100,000 cattle tested in 1983 to 158 per 100,000 in 1994. CONCLUSION: The low
      incidence plateau of human tuberculosis due to M. bovis together with the decline
      in prevalence of animal infection in the overall period studied suggest a cut-off
      in the animal to human chain of infection at two points; the animal source and
      the ingestion of (now pasteurized) milk. This would suggest that disease in
      humans is now due to reactivation of previous foci of infection which were
      acquired when milk pasteurization was not compulsory. Based on this, we would
      anticipate a further reduction and possible elimination of human tuberculosis due
      to M. bovis in this region in the next 10-15 years.

PMID- 9039449
TI  - The rapid village survey in tuberculosis control.
AB  - SETTING: Khon Kaen Province, North-East Thailand. OBJECTIVE: To develop a rapid
      and cheap method of surveying a population cluster (a village) to establish the
      prevalence of sputum-positive tuberculosis. DESIGN: Based on previous experience
      a standardized 'rapid village survey' method was designed and tested. In this
      method a survey team of health workers is constituted and trained. Before and at
      the beginning of a visit to a village the population receives information about
      tuberculosis, and only individuals with chest symptoms are invited to report
      voluntarily to the survey team for examination. Active tracing of a previously
      compiled 'list of suspects and contacts' complements the identification of cases.
      The number of community members to be examined is thus much lower. A cluster
      sample of the provincial population was made (20,730 people in 40 villages). The
      population in each village was surveyed first by the Rapid Village Survey method,
      then, 1 week later, by the conventional method of examining every individual
      registered in each village. RESULTS: In the rapid village survey 14 cases of
      sputum-positive tuberculosis were detected and in the conventional survey 15
      cases. CONCLUSION: The rapid method produces results comparable to the survey of
      the total sample population for less than half of the cost.

PMID- 9039450
TI  - Urinary tract infection caused by Mycobacterium terrae complex.
AB  - We describe a case of recurrent urinary tract infection caused by Mycobacterium
      terrae complex in a patient with obstructive nephropathy. The mycobacterium was
      resistant to most antituberculosis drugs and despite its apparent clearance in
      the urine, the patient finally died of urinary sepsis caused by multiple
      bacterial pathogens.

PMID- 9039451
TI  - Rifampicin-induced immune thrombocytopenia.
AB  - Rifampicin-induced thrombocytopenia is reported in three patients with pulmonary
      tuberculosis. All three patients gave a definite history of having had prior
      exposure to rifampicin. Immunological studies in all three patients showed the
      presence of antiplatelet antibodies, resulting in thrombocytopenia. Moreover,
      binding of these antibodies to the platelet membrane was more avid in the
      presence of rifampicin, thereby implicating the drug. The avidity of the
      rifampicin-dependent antibodies was demonstrated by platelet aggregation
      inhibition test, and estimation of the rifampicin-dependent antibody was done by
      studying the platelet-associated immunoglobulin [PAlgG] by ELISA which was also
      used to quantitate antiplatelet antibodies. Immunofluorescence test was also
      performed to detect antiplatelet antibodies.

PMID- 9039452
TI  - Retropharyngeal abscess associated with tuberculosis of the cervical spine.
AB  - A rare case of retropharyngeal abscess in association with tuberculosis of the
      upper cervical spine is presented. The disease was associated with tuberculosis
      of the sternum. The onset was insidious. Fever, neck pain, dysphagia and
      hoarseness of voice were the presenting features. Conservative treatment with
      anti-tuberculosis drugs resulted in good outcome. The case is discussed and
      pertinent literature is reviewed.

PMID- 9039453
TI  - Cystic tuberculosis of the bone mimicking osteogenic sarcoma.
AB  - Hong Kong has a relatively high incidence of tuberculosis in comparison with
      other developed cities, possibly due to the influx of mainland Chinese immigrants
      and Vietnamese boat people. However, primary, solitary cystic tuberculous
      infection of the bone is rare and few cases have been reported. Radiological
      appearances of this disease can mimic several bone conditions, including bone
      cyst, osteoblastoma and even osteosarcoma. We report on a case of a healthy
      fifteen-year-old who presented with swelling to the left elbow; biopsy confirmed
      this as cystic tuberculosis of the bone.

PMID- 9039454
TI  - Splenectomy in a patients with AIDS, generalized Mycobacterium genavense
      infection and severe pancytopenia.

PMID- 9039455
TI  - Cigarette smoking as a risk factor for tuberculosis in young adults: a case
      control study.

PMID- 9039456
TI  - On the question of apoptosis in the parkinsonian substantia nigra.
AB  - Apoptosis has been postulated as a mechanism of nerve cell death in Parkinson's
      disease. In the present study, the substantia nigra of 22 neuropathologically
      confirmed Parkinson cases and 8 control brains was studied using the in situ end
      labeling (TUNEL) method. About 50% of parkinsonian brains showed a small number
      of TUNEL-positive glial cells in the substantia nigra, whereas no neurons showed
      convincing TUNEL positivity or any morphological signs of apoptosis. No
      correlation was observed between the number of TUNEL-positive glial cells and
      microglial activation. Our results fail to demonstrate apoptosis as a mechanism
      of cell death in Parkinson's disease.

PMID- 9039457
TI  - Expression and distribution of vascular endothelial growth factor protein in
      human brain tumors.
AB  - Marked neovascularization is a hallmark of many neoplasms in the nervous system.
      Recent reports indicate that the endothelial mitogen vascular endothelial growth
      factor (VEGF) may play a critical role in the regulation of vascular endothelial
      proliferation in malignant gliomas. Using novel monoclonal antibodies to the VEGF
      polypeptide we have determined the expression and cellular distribution of VEGF
      protein in a representative series of 171 human central nervous system (CNS)
      tumors by immunohistochemistry and immunoblotting. In agreement with previous in
      situ hybridization data, 19 out of 20 glioblastomas (95%) showed immunoreactivity
      for VEGF, whereas both the percentage of immunoreactive tumors and the extent of
      immunoreactivity for VEGF were significantly lower in astrocytomas. Of the
      pilocytic astrocytomas (WHO grade I) 44% were immunoreactive for VEGF, but we
      observed several cases with pronounced vascular proliferates in the absence of
      VEGF. In ependymomas, meningiomas, hemangioblastomas, and primitive
      neuroectodermal tumors, there was no correlation between VEGF expression,
      vascular endothelial proliferation and the grade of malignancy.
      Oligodendrogliomas and the oligodendroglial component of mixed gliomas lacked
      immunoreactive VEGF, indicating that endothelial growth factors other than VEGF
      may regulate tumor angiogenesis in these neoplasms. Western blot analysis showed
      a predominant VEGF protein species of 23 kDa and confirmed the
      immunohistochemical data in all cases. Our findings demonstrate that VEGF is
      expressed in a wide spectrum of brain tumors in which it may induce
      neovascularization. However, other angiogenic factors also appear to contribute
      to the vascularization of CNS neoplasms.

PMID- 9039458
TI  - Neuropathology and blood flow of nerve, spinal roots and dorsal root ganglia in
      longstanding diabetic rats.
AB  - Vascular perfusion and neuropathologic evaluation of the lumbar spinal roots and
      dorsal root ganglia (DRG) were studied in rats with longstanding (duration 12-15
      months) streptozotocin-induced diabetes and age- and sex-matched control rats. We
      also undertook nerve conduction studies including F-wave recordings and measured
      blood flow in sciatic nerve, DRG, and superior cervical ganglion (SCG). Light
      microscopically, changes of the myelin sheath in the dorsal and ventral roots and
      vacuolated cells in the DRG were the major findings, being significantly higher
      in diabetic rats than in control rats. The effects of the diabetic state on
      myelin splitting were greater in the dorsal than ventral roots. Electron
      microscopic studies revealed a gradation of changes in myelin from mild
      separation to severe ballooning of myelin with relative axonal sparing. DRG cells
      showed vacuoles of all sizes with cristae-like residues, suggestive of
      mitochondria. These findings suggest that diabetes mellitus has a dual effect: it
      accelerates the normal age-related degenerative changes in the spinal roots and
      DRG, and it also has a selective effect on the sensory neuron. Nerve conduction
      studies showed markedly reduced conduction velocities in the distal nerve
      segments and prolonged F-wave latency and proximal conduction time despite the
      shorter conduction pathway in diabetic rats. Blood flow, which was measured using
      iodo[14C]antipyrine autoradiography, was significantly reduced in the sciatic
      nerves, DRG, and SCG of diabetic rats. We suggest that the combination of
      hyperglycemia and ischemia results in oxidative-stress and a predominantly
      sensory neuropathy.

PMID- 9039459
TI  - Denervation-induced region-specific changes in fibre types in the soleus and
      plantaris muscles of rats.
AB  - Muscle fibre composition was compared among the proximal (25%), middle (50%) and
      distal (75%) regions of muscle to investigate whether denervation induces region
      specific changes of fibre types in the soleus and plantaris muscles of rats.
      Decreases in mass were observed in both muscles after denervation. In the soleus
      muscle, denervation increased the percentage of type I fibres with a concomitant
      increase in the proportion of type IIC and IIA fibres. The extent of such
      transformations was greater in the proximal region than the middle and distal
      regions. In normal plantaris muscle, the middle region showed a higher proportion
      of type IIA fibres with a lower percentage of type IIB fibres reciprocally than
      other regions. These regional differences in fibre types were not detected in the
      4-week denervated plantaris muscle. These findings suggest that denervation
      induced transformations from type I to type II fibres begin in the proximal
      region in the soleus muscle of rats. In addition, regional differences in fibre
      types along the muscle length could be regulated by neuromuscular activity
      through normal innervation in the plantaris muscle.

PMID- 9039461
TI  - Cholinergic fibre loss associated with diffuse plaques in the non-demented
      elderly: the preclinical stage of Alzheimer's disease?
AB  - Diffuse plaques are the earliest Alzheimer-type lesions in Down's syndrome and
      are a putative marker for the preclinical stage of Alzheimer's disease (AD). As a
      cerebral cortical cholinergic deficit is one of the characteristics which defines
      AD, we examined the brains of individuals who had died without a history of
      neurological disease to determine whether this deficit is present in association
      with diffuse plaques. Of the 24 cases collected, 14 were older than 60 years of
      age (mean 69.2 years) and 10 were younger (mean 29.6 years). Of the 14 older
      cases, 9 had diffuse plaques in the entorhinal cortex (ECx) and/or inferior
      temporal gyrus (ITG). The older cases were divided into two groups (plaque
      positive or plaque-negative cases). These groups did not differ significantly
      with respect to age, post-mortem delay, synaptophysin immunoreactivity or
      neurofibrillary tangle density. Cholinergic fibre densities were estimated in
      sections stained using acetylcholinesterase (AChE) enzyme histochemistry. Mean
      AChE fibre density was decreased in both the ITG and ECx (approximately 30% and
      50% depletion, respectively) in the plaque-positive group compared to the plaque
      negative group and in both areas the mean fibre density of the plaque-positive
      group was about 50% of that in the younger group. These results suggest that
      diffuse plaques in the non-demented elderly are associated with an accelerated
      age-related cortical cholinergic deficit and, therefore represent the preclinical
      stage of AD.

PMID- 9039460
TI  - Microencephaly in children congenitally infected with human immunodeficiency
      virus--a gross-anatomical morphometric study.
AB  - A quantitative technique involving serial sectioning and semiautomatic
      morphometric analysis was used to assess the severity of the reduction in size of
      the major brain structures in cerebral hemispheres of children congenitally
      infected with HIV-1. Cerebral hemispheres from 12 children (18-48 months of age)
      who died of AIDS were sectioned into 5-mm-thick serial slabs and photographed.
      The cross-sectional areas of grossly recognizable brain structures were
      digitized, and the volumes were calculated according to Cavalieri's principle.
      The results were compared with those of an identically processed group of control
      brains from non-AIDS children. Analysis of the brain weight showed that there was
      a significant reduction in supratentorial and infratentorial weight in the AIDS
      group. The results of the morphometric study revealed that the loss in brain mass
      was associated with a statistically significant reduction in the total volume of
      both hemispheres, the entire cortex, white matter, and basal ganglia. Detailed
      analysis of individual brain structures also showed a significant reduction in
      volume of all cortical regions and most of the subcortical gray matter (e.g.,
      caudate nucleus, putamen, globus pallidus, claustrum, and thalamus). It appears
      that in the microencephaly observed as a frequent sequel in pediatric AIDS, the
      loss of brain tissue is global and includes an almost proportional loss of
      cortex, subcortical gray matter and white matter.

PMID- 9039462
TI  - Induction of cytokines, chemokines and adhesion molecule mRNA in a rat forebrain
      reperfusion model.
AB  - Cellular damage secondary to reperfusion following ischemic insult has been
      hypothetically attributed to an inflammatory cascade concerted by cell-to-cell
      interactions. While the role of several cytokines and adhesion molecules in
      reperfusion injury of the brain has been explored to a certain extent, their
      regulatory and temporary profiles remain unclear. We have addressed the temporal
      features of the induction of mRNA for proinflammatory cytokines, adhesion
      molecules and chemokines at an acute phase subsequent to reperfusion in rat
      forebrain. Semiquantitatively calibrated reverse transcription-polymerase chain
      reaction analysis was employed to assess the relative expression of mRNA for
      intercellular adhesion molecule (ICAM)-1, interleukin (IL)-1 alpha, IL-1 beta, 1L
      2, 1L-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, monocyte
      chemoattractant protein (MCP)-1, and macrophage migration inhibitory factor
      (MIF). The increase in mRNA from the basal levels after reperfusion followed one
      of two different patterns; an increase occurring as early as 1 h, or a slight
      increase continuing up to 24 h after reperfusion. The former pattern was seen for
      ICAM-1, IL-1 alpha, IL-1 beta, TNF-alpha, and MCP-1, and the latter for IL-6 and
      MIF. These results were consistent with the proinflammatory properties of the
      immediately induced cytokines, which may be involved in the initiation step of
      the inflammatory cascade, causing the secondary cellular responses and finally
      leading to further brain damage.

PMID- 9039463
TI  - Increasing or decreasing nervous activity modulates the severity of the glio
      vascular lesions of 1,3-dinitrobenzene in the rat: effects of the tremorgenic
      pyrethroid, Bifenthrin, and of anaesthesia.
AB  - To test the hypothesis that altered neuronal activity may influence the extent
      and severity of the glio-vascular lesions produced by 1,3-dinitrobenzene (DNB),
      rats were either given the tremorgenic pyrethroid, Bifenthrin, or anaesthetised
      during various dosing schedules of DNB. When compared with controls dosed only
      with DNB, Bifenthrin tremor made both the ataxia and other functional effects
      caused by DNB more pronounced. Lesions in the brain stem were made significantly
      more severe and widespread across three dose levels of DNB. Centres such as
      facial nuclei, motor nuclei of fifth nerve, subthalamic nuclei and mamillary
      bodies, not damaged by DNB alone, were also affected in some animals. In
      contrast, general anaesthesia by either isoflurane ur urethane decreased the
      severity of the lesions, this being more pronounced with urethane. The character
      of the tissue changes, however, was not altered by these additional procedures.
      These findings support the suggestion that neuronal activity is one important
      determinant of the selective vulnerability of sensitive brain stem nuclei to glio
      vascular damage from DNB intoxication.

PMID- 9039465
TI  - Spatial and temporal development of the gliovascular tissue in type II
      lissencephaly.
AB  - Type II lissencephaly is a complex cortical malformation in which mesenchymal and
      central nervous components are intermingled. It is generally believed that the
      histological pattern is created by migration of heterotopic neuroblasts into the
      leptomeninges through defects in the superficial basement membrane. Defects of
      the extracellular matrix have been suggested to be the primary cause of type II
      lissencephaly. To elucidate the underlying pathogenetic mechanisms, we
      immunostained extracellular matrix and basement membrane components of the
      cerebral cortex from six fetal and two infantile brains. We found that the
      pattern of collagen subtypes I, III and VI was not altered in type II
      lissencephaly brains when compared to normal controls. As to the pathogenesis of
      type II lissencephaly, a polymicrogyria-like pattern is created, which results in
      considerable cortical enlargement. The microgyri do not fuse but remain separated
      from each other by gliovascular tissue, i.e., leptomeninges which contain
      astrocytes. At the interface between the enlarged brain surface and the
      gliovascular tissue, neuronal migration takes place through gaps in the external
      basement membrane. Thus, the cortical dysplasia encountered in type II
      lissencephaly is only due to a limited amount to neuronal heterotopia in the
      leptomeninges.

PMID- 9039464
TI  - Localization of the laminin alpha 2 chain in normal human skeletal muscle and
      peripheral nerve: an ultrastructural immunolabeling study.
AB  - A particular form of congenital muscular dystrophy is associated with a
      deficiency of the tissue-specific basement membrane protein laminin alpha 2. A
      more precise knowledge of the normal distribution and localization of laminin
      alpha 2 would be useful in further elucidating the development of this disorder.
      In this study we used specific electron microscopic techniques, i.e., thin
      section fracture labeling and cryoultramicrotomy in combination with immunogold
      labeling for laminin alpha 2, to determine its ultrastructural localization in
      normal human muscle and peripheral nerve. Both in muscle and in peripheral nerve,
      laminin alpha 2 is found to be associated solely with the basal lamina of
      myofibers and Schwann cells, respectively. Of special interest is the finding
      that in peripheral nerve, laminin alpha 2 is associated only with myelinated and
      not with unmyelinated nerve fibers.

PMID- 9039466
TI  - Spinal muscular atrophy in Holstein-Friesian calves.
AB  - The clinical and neuropathological findings of spinal muscular atrophy (SMA) in
      Holstein-Friesian calves are described in four females and one male from a dairy
      farm composed of 150 cows and 2 breeding bulls. Locomotion difficulties started
      at the age of 15 days, and progressed to paraparesis and tetraparesis in 2 weeks.
      Signs consistent with denervation were revealed with electromyography. The
      neuropathological examination showed degeneration and loss of motor neurons in
      the spinal cord, together with astrocytosis. Among the remaining motor neurons
      were ghost cells and neurons filled with accumulations of straight filaments
      measuring 10-12 nm in diameter, which were strongly immunoreactive with
      antibodies produced against phosphorylated neurofilaments. Degenerating cells in
      SMA did not stain with the method of in situ labelling of nuclear DNA
      fragmentation and did not show c-Jun immunoreactivity. This feature contrasts
      with the in situ labelling of DNA breaks of apoptotic cells and with the strong c
      Jun immunoreactivity restricted to dying cells during the whole process of
      naturally occurring cell death in the developing central nervous system. These
      features suggest that cell death in SMA differs from programmed cell death during
      normal development, and that pathological cell death in SMA should not be
      considered as a mere persistence or reactivation of normally occurring
      developmental cell death.

PMID- 9039467
TI  - Cerebral white matter damage in HIV infection demonstrated using beta-amyloid
      precursor protein immunoreactivity.
AB  - We have examined brain sections from 55 autopsy cases of AIDS for the prevalence
      and severity of axonal damage, assessed using beta-amyloid precursor protein
      (beta APP) immunoreactivity as a marker of such damage. The cases were subdivided
      into cases with HIV encephalitis with multinucleated giant cells (MGC), cases
      with other specific pathology, such as cerebral toxoplasmosis or lymphoma, cases
      with non-specific pathology and cases with no pathology. Significantly more foci
      containing beta APP+ axons were found in cases with HIV encephalitis with MGC
      (80%) and in cases with other specific pathology (58%) than in those with non
      specific (30%) or no pathology (30%). The prevalence and abundance of beta APP+
      axons generally paralleled the severity of pallor of myelin staining of cerebral
      white matter in cases without other specific pathology but in 4 cases without any
      pallor of myelin staining beta APP+ axons were present, suggesting that it may be
      a more sensitive marker of some forms of white matter damage in HIV infection
      than myelin pallor. Foci of beta APP+ axons were found in subcortical and deep
      white matter but did not convincingly co-localise with foci of demonstrable HIV
      infection as indicated by the presence of MGC and HIV p24 immunoreactivity. In
      contrast, they showed an approximately perivascular distribution at some sites in
      all of the disease categories studied. We consider this localisation to be more
      suggestive of a vascular pathogenetic mechanism of deep white matter damage in
      HIV infection than a mechanism dependent on diffusion of local myelinotoxic
      products from foci of cerebral HIV infection.

PMID- 9039468
TI  - Chronic histopathological consequences of fluid-percussion brain injury in rats:
      effects of post-traumatic hypothermia.
AB  - Early outcome measures of experimental traumatic brain injury (TBI) are useful
      for characterizing the traumatic severity as well as for clarifying the
      pathomechanisms underlying patterns of neuronal vulnerability. However, it is
      increasingly apparent that acute outcome measures may not always be accurate
      predictors of chronic outcome, particularly when assessing the efficacy of
      potential therapeutic regimens. This study examined the chronic histopathological
      outcome in rats 8 weeks following fluid-percussive TBI coupled with moderate post
      traumatic brain hypothermia, a protocol that provides acute neuronal protection.
      Animals received a moderate parasagittal percussive head injury (2.01-2.38 atm)
      or sham procedure followed immediately by 3 h of brain hypothermia (30 degrees C)
      or normothermia (37 degrees C). Eight weeks following TBI, serial tissue sections
      were stained with hematoxylin and eosin or immunostained for glial fibrillary
      acidic protein. Tissue damage, gliosis and immunoreactive astrocytes were
      observed in the ipsilateral thalamus, hippocampus, and in the neocortex lateral
      to the injury site. Within the thalamus, focal necrosis was restricted to
      selective thalamic nuclei. Significant hippocampal cell loss was found in the
      ipsilateral dentate hilar region of both TBI groups. Quantitative volume
      measurements revealed significant decreases in cortical, thalamic and hippocampal
      volume ipsilateral to the impact in both TBI groups. Lateral ventricles were
      substantially enlarged in the TBI-normothermia group, an effect which was
      significantly attenuated by post-TBI hypothermia. The attenuation of lateral
      ventricular dilation by post-traumatic hypothermia is indicative of chronic
      neuroprotection in this TBI model. These data provide new information concerning
      the chronic histopathological consequence of experimental TBI and the relevance
      of this trauma model to chronic human head injury.

PMID- 9039469
TI  - Melanotic cerebral astrocytoma: case report and literature review.
AB  - We describe the case of 47-year-old man with a cystic, melanotic temporal lobe
      astrocytoma who had a history of complex partial seizures. The tumor mass was
      made up of two histologically different regions: one consisted of spindle-shaped
      and pleomorphic cells often with foamy or vacuolated cytoplasm, while the other
      consisted of fairly uniform spindle-shaped cells, many of which contained dark
      brown intracytoplasmic pigment. Desmoplasia was also noted in the latter region
      of the tumor. No features suggestive of malignancy, such as mitotic figures,
      necrotic foci or endothelial vascular proliferation, were observed throughout the
      tumor. Immunohistochemically, the tumor cells in both regions were positive for
      glial fibrillary acidic protein. Ultrastructural examination of the pigmented
      region showed the presence of melanosomal melanin in the tumor cells. Apart from
      the partial pigmentation, the entire histological picture resembled a pleomorphic
      xanthoastrocytoma. To our knowledge, only two cases of similar melanotic
      astrocytic tumors have been described previously. Interestingly, the astrocytic
      tumors in both of these patients were also clinically associated with epilepsy,
      were located in the temporal lobe, and were histologically benign.

PMID- 9039470
TI  - Multiple sclerosis and amyloid deposits in the white matter of the brain.
AB  - We present the neuropathological findings in a female patient with clinically
      definite multiple sclerosis (MS), who at autopsy had multifocal amyloid deposits
      in the white matter of the brain without other signs of amyloidosis. The patient
      had relapsing/remitting MS between the ages of 26 and 45, and during her last 14
      years she had a secondary chronic progressive form of MS. Previous reports of
      amyloid deposits in MS are reviewed and the possible relationship between amyloid
      deposits and the increased production of immunoglobulin free light chains in MS
      is discussed.

PMID- 9039471
TI  - The ultrastructure of skin from a patient with mucopolysaccharidosis IIID.
AB  - Mucopolysaccharidosis IIID (MPS-IIID) is the rarest of the MPS-III syndromes. It
      is caused by deficient activity of lysosomal N-acetylglucosamine-6-sulfatase
      (G6S). To date, the clinical and biochemical features of seven patients with MPS
      IIID have been reported, but no biopsy or autopsy findings have been described.
      The purpose of this report is to define the ultrastructure of affected cells seen
      in a skin biopsy from a 14-year-old boy. The child presented with progressive
      mental deterioration, hyperactivity and mild to moderate dysmorphism. The
      diagnosis of a mucopolysaccharidosis was suggested, but the initial urine
      analyses were negative for elevated mucopolysaccharides, and only the third
      analysis showed abnormal excretion of heparan sulfate. Because of the diagnostic
      difficulties posed by this case, a skin biopsy was performed for morphological
      and biochemical studies. Numerous vacuoles were noted in Schwann cells,
      fibroblasts, smooth muscle cells, eccrine gland and ductal epithelium in resin
      embedded sections stained with toluidine blue. Ultrastructurally, many lysosomes
      were distended with abundant, fibrillar material. Occasionally, lamellated
      membranous structures were present within the same lysosomes. These findings are
      consistent with those seen in other forms of MPS, in which the lysosomal storage
      occurs predominantly, but not exclusively, in mesenchymal cells. Furthermore,
      deficient activity of G6S was confirmed in cultured skin fibroblasts. This study
      demonstrates that electron microscopy of skin biopsies is a useful method for
      identification of patients with clinical features of MPS-IIID whether or not
      heparan sulfaturia is present.

PMID- 9039472
TI  - Deviation of the subjective vertical in long-standing unilateral vestibular loss.
AB  - We evaluated changes in the subjectively perceived gravitational vertical as an
      index of imbalance in the function of the right and left otolith organs. In
      addition to normal subjects (n = 25), we measured patients with a longstanding
      (mean 4.5 year +/- 3.2 SD; range 0.5-11.5 years) unilateral vestibular loss after
      surgery for acoustic neuroma (n = 32), patients with partial unilateral
      vestibular loss (n = 7) and patients with bilateral vestibular hyporeflexia (n =
      8). Normal subjects could accurately align a vertical luminous bar to the
      gravitational vertical in an otherwise completely dark room (mean setting -0.14
      degree +/- 1.11 SD). Patients with left-sided (complete; n = 13) or right-sided
      (complete; n = 19 and partial; n = 7) unilateral vestibular loss made mean
      angular settings at 2.55 degrees +/- 1.57 (SD) leftward and 2.22 degrees (+/-1.96
      SD) rightward, respectively. These means differed highly significantly from the
      normal mean (p < 0.00001). In the time interval investigated (0.5-11.5 years) the
      magnitude of the tilt angle showed no correlation with the time elapsed since the
      operation. The mean setting by patients with clinically bilateral vestibular loss
      (-1.17 degrees +/- 1.96 SD; n = 8) did not significantly differ from the control
      group. The systematic tilts of the subjective vertical in patients with a
      unilateral vestibular impairment were correlated with their imbalance in canal
      ocular reflexes, as reflected by drift during head-oscillation at 2 Hz (r2 =
      0.44) and asymmetries in VOR-gain for head-steps (r2 = 0.48-0.67). These
      correlations were largely determined, by the signs of the asymmetries;
      correlation between the absolute values of the VOR gain asymmetries and
      subjective vertical angles proved to be virtually absent. We conclude that the
      setting of the subjective vertical is a very sensitive tool in detecting a left
      right imbalance in otolith function, and that small but significant deviations
      towards the defective side may persist for many years (probably permanently)
      after unilateral lesions of the labyrinth or the vestibular nerve.

PMID- 9039473
TI  - Unilateral vestibular neuritis with otolithic signs and off-vertical axis
      rotation.
AB  - Off-vertical axis rotation (OVAR) at constant velocity is a dynamic otolith
      stimulus that induces horizontal and vertical eye movement responses. To
      determine the value of this examination as a test for unilateral otolithic
      hypofunction, we compared the OVAR responses of patients suffering from acute
      vestibular neuritis (VN) without any sign of otolith affection, with those of
      patients suffering from acute VN with otolithic signs. The horizontal eye
      movement bias component shows directional preponderance (DP) significantly higher
      in patients with otolithic signs than in patients not presenting them. However,
      as bias DP also reflects the imbalance between right and left horizontal canals
      activity, this greater bias DP could be explained by the more severe canals
      impairment-evaluated by caloric test-found in patients with otolithic signs. No
      significant difference can be shown on horizontal modulation. The DP of vertical
      modulation is significantly higher in patients presenting otolithic signs than in
      patients not presenting them: in the case of otolithic signs, the responses are
      smaller during rotations toward the affected side. Therefore, this variable could
      be used as an indication of unilateral otolithic hypofunction.

PMID- 9039474
TI  - Two-phase endolymphatic hydrops: a new dynamic guinea pig model.
AB  - The classical guinea pig model for Meniere's disease, in which endolymphatic
      hydrops was achieved by destruction of the endolymphatic sac and obliteration of
      the endolymphatic duct, is a non-physiological profound model with shortcomings
      in relation to Meniere's disease as seen in patients. We developed a more subtle
      animal model; the two-phase endolymphatic hydrops. This model is based on a
      combination of chronic endolymphatic sac dysfunction, induced by slight
      destruction of the most distal part of the endolymphatic sac, and acute stress
      induced endolymph production by stimulation of the Na/K-ATPase in the stria
      vascularis with aldosterone. Light microscopy of the fluid compartments of four
      groups of cochleas was used to examine them for the presence of endolymphatic
      hydrops: i) Normal (control) cochleas showed no hydrops; ii) some of the non
      operated (no destruction) aldosterone-treated cochleas showed small degrees of
      hydrops mainly present in the basal turns; iii) mild dissection of the
      endolymphatic sac without administration of aldosterone produced a hydrops which
      was mainly present in the cochlear apex; iv) combination of chronic endolymphatic
      sac dysfunction and acute attacks of endolymph production by aldosterone
      administration revealed the most severe degrees of hydrops in all cochlear
      windings, damage to cochlear structures, and cellular disturbances of the
      epithelial lining of the endolymphatic sac. This new model may represent a more
      physiologic and dynamic approach to Meniere's disease and may explain the
      etiology of many symptoms in patients such as the fluctuant nature and the types
      of sensoneuronal hearing losses.

PMID- 9039475
TI  - Degenerative hairlets on the vestibular sensory cells in mutant bustling
      (BUS/Idr) mice.
AB  - The bustling mouse (BUS/Idr: bus) is a mutant mouse strain which exhibits
      deafness, bustling/hyperkinetic behaviour and functional disorders seemingly
      related to the vestibular system. This phenotype develops in homozygous (bus/bus)
      mice and has been shown from cross experiments to be genetically induced by a
      single autosomal recessive gene. We previously detected, with light and electron
      microscopy, post-natal degeneration of the inner ear sensory cells in
      homozygotes. In the present study, we examined, by electron microscopy, the
      development of pathological changes in the sensory epithelia of the macula
      acustica and crista ampullaris of homozygous mice of various ages, paying special
      attention to the detailed morphology of the sensory hairlets. The homozygous mice
      exhibited specific pathological changes: a decrease in the number of hairs;
      disarrangement of the kinocilium-stereocilia pattern; and, fused and/or very
      large stereocilia. Homozygotes also frequently exhibited apical cytoplasmic
      herniation, or bleb of hair cells, as well as a degenerated kinocilium in the
      sensory epithelium. Heterozygotes showed similar changes, but to a lesser degree
      and frequency. As for the vestibular organs, similar pathological changes had
      developed at day, 17 of gestation. These pathological findings and onset suggest
      that the BUS mouse may be a mutant mouse strain distinct from other reported
      strains which display similar behaviour, and may be a useful animal model for the
      study of human degenerative vestibular disorders.

PMID- 9039476
TI  - Characteristics of transient-evoked otoacoustic emissions (TEOES) in neonates.
AB  - Transient-evoked otoacoustic emissions (TEOEs) were measured in 1164 ears from
      582 neonates without any risk of hearing impairment in order to define basic
      characteristics useful in deciding if TEOEs could be considered as "normal" in a
      screening test. Five neonates had no recordable TEOE and ABR thresholds greater
      than 30 dBnHL. Technical conditions have been analysed using the intensity of the
      click stimulation, the time necessary to record TEOEs, and the noise floor in the
      external ear canal (i.e. A-B magnitude). The TEOE magnitude varied between 6.6 dB
      SPL and 38 dB SPL (mean = 21.75 dB SPL). Only 5% of the tested neonates had a
      TEOE magnitude lower than 7.75 dB SPL. The TEOE magnitude for the right ear of a
      neonate was statistically different from those recorded in the left ear (22.4 dB
      SPL versus 21 dB SPL). The mean TEOE magnitude for male ears was statistically
      different from those recorded in female ears (21.4 dB SPL versus 22.1 dB SPL).

PMID- 9039477
TI  - Tinnitus remission by lidocaine demonstrated by auditory-evoked
      magnetoencephalogram. A preliminary report.
AB  - An auditory-evoked magnetic field was recorded before and during tinnitus
      remission induced by an intravenous lidocaine injection. One and 4 kHz probe
      tones were presented monaurally in four tinnitus patients, and the responses were
      recorded using a 122-channel magnetometer. Three normal volunteers were also
      examined as controls. In tinnitus patients, the N100 m peak became sharper, while
      there was no marked change except for slight reduction in amplitude in normal
      subjects. Tinnitus remission by lidocaine may be related to attenuation of a
      masking-like effect of tinnitus on the sound-evoked responses.

PMID- 9039478
TI  - Thallium chloride 201Tl combined with single photon emission computed tomography
      (SPECT) in the evaluation of vestibular schwannoma growth.
AB  - Thallium chloride 201Tl combined with SPECT was performed in a series of 29
      patients with neuroradiological evidence of vestibular schwannoma (VS). The
      relative tumor uptake (U) and relative tumor concentration (C) of the radiotracer
      201Tl was determined, and the cerebellum served as a reference. The relative
      tracer concentration and uptake were correlated to tumor volume determined by
      gadolinium DTPA enhanced MR, to prediagnostic duration of symptoms, to tumor
      vascularity expressed by the average number of intratumoral vessels using the
      endothelial marker CD31, and to the proliferative activity in the tumors
      expressed by positive staining with the monoclonal antibody MIB-1 for Ki-67. A
      positive 201TI enhancement was detected in 17 tumors (n = 17). Tumors U and C
      were statistically unrelated to tumor volume (p = 0.236 and p = 0.439). SPECT
      demonstrated all tumors > 0.8 cm3, but it had its limitation as a diagnostic
      modality of small intracanalicular tumors, when compared with gadolinium DTPA
      enhanced MR. Relating U and C in all tumors (n = 29) and the prospectively
      registered data on the prediagnostic duration of symptoms, a statistical
      significance was found (p = 0.012 and p = 0.015). No statistically significant
      correlation was observed between U and C and the proliferative activity of the
      tumors expressed by positive staining with the monoclonal antibody MIB-1 for Ki
      67 (p = 0.063 and p = 0.086). A statistically significant correlation was noted
      between C and U in the operated group (n = 12) and tumor vascularity expressed by
      the average number of the intratumoral vessels (p = 0.003 and p = 0.014). SPECT
      was found to be superior to MR in determining VS growth potentials as it
      expresses tumor vascularity, which is essential for tumor growth. It seems that
      we now have an in vivo functional radiological modality capable of providing data
      on VS vascularity and determination of growth potential in the individual tumor.
      A high radioactive tracer uptake in the tumor corresponded to high tumor
      vascularity, indicating a high growth rate and vice versa.

PMID- 9039479
TI  - Distribution of endothelin-1-like activity in the cochlea of normal guinea pigs.
AB  - Distribution of endothelin-1 (ET-1) in the cochlea of normal guinea pigs was
      determined by immunohistochemistry. ET-1 activity was identified with the mouse
      anti-human ET-1 IgG1 monoclonal antibody. ET-1 activity was distributed in the
      modiolus, spiral ligament, stria vascularis, spiral prominence. Reissner's
      membrane, supporting cells of the organ of Corti and spiral ganglion cells. These
      findings suggest that ET-1 may be involved in the regulation of fluid volume and
      ions of the cochlea.

PMID- 9039480
TI  - Quinine-induced hearing loss in the guinea pig is not affected by the Ca2+
      channel antagonist verapamil.
AB  - It is well documented that quinine induces reversible hearing loss and tinnitus.
      The purpose in this study was to induce a quinine hearing loss and to investigate
      if verapamil, a Ca2+ channel antagonist of L-type might affect the response.
      Pigmented guinea pigs (n = 24) were anaesthetized by atropine. Hypnorm and
      midazolam but permitting spontaneous respiration. An electrode of platinum was
      placed on the round window and short (10 msec) tone pulses at 8 kHz were
      presented to the external ear. A typical deflection of the N1-wave was determined
      as the hearing threshold. Quinine hydrochloride 40 mg/kg and verapamil 1 mg/kg
      were given intravenously. Quinine induced a significant and reversible hearing
      loss (mean 16 dB). This hearing loss was not at all affected by verapamil given
      before or after quinine. Verapamil often caused acute cardiac arrest and
      particularly the combination verapamil followed by quinine-induced death to the
      animal. We conclude that verapamil and quinine had no in vivo interaction with
      regard to the hearing ability.

PMID- 9039481
TI  - Effects of local anaesthetics on the gross receptor potentials in the guinea pig
      cochlea.
AB  - Local anaesthetics have been used intravenously and intratympanally to reduce
      tinnitus. In order to clarify its action in the periphery, we applied 0.5 mM
      tetracaine in the scala tympani in 18 cochleae and studied the effects on the
      receptor potentials. We used a temporal bone preparation of the guinea pig ear in
      vitro exposing the fourth cochlear turn where the cochlear microphonics (CM) and
      the summating potential (SP) were recorded. The perfusion was kept at a rate of
      50 microliters/min. The frequency response of the cochlea was determined at the
      beginning of each experiment and the responses were recorded at the best
      frequency of the preparation. In another five cochleae an accumulated dose
      response relationship was determined by increasing the tetracaine concentration
      in steps (50, 100, 300, 500, 1000 and 2000 microM), measuring the difference in
      amplitude of the receptor potentials. The CM decreased significantly (p < 0.001;
      mean 0.37 mV; SD 0.29). In 12 cochleae the SP was initially positive and did not
      increase significantly (p = 0.16; mean 0.07 mV; SD 0.16). In six cochleae the SP
      was initially negative and all changed polarity to positive and increased
      significantly (p < 0.05; mean 0.36 mV; SD 0.28). The effects on both the CM and
      the SP were reversible. Owing to the inter-individual variation between the
      cochleae the SP/CM ratio was determined and it increased significantly (p <
      0.001; mean 0.18; SD 0.11). In the accumulated dose-response experiments the CM
      decreased significantly (p < 0.05) in a dose-dependent way, whereas the SP did
      not increase significantly. The SP/CM ratio increased significantly (p < 0.05) at
      300 microM and 500 microM. We hypothesize that the peripheral tinnitus-reducing
      action of local anaesthetics is in part due to a reversal of the SP, but also to
      a reduction of the CM. The difference in effect of tetracaine on the receptor
      potentials, the CM and the SP, suggests that the SP is not dependent on the CM.

PMID- 9039482
TI  - Blood flow-independent accumulation of cisplatin in the guinea pig cochlea.
AB  - Considerable interindividual variability in the ototoxic effect of cisplatin has
      become the unpredictable dose-limiting factor in its use as curative as well as
      palliative therapy. The drug accumulates in highly vascular areas in the cochlea,
      causing dose-related hair cell loss. The purpose of this study was to assess
      blood flow-dependent aspects of cisplatin absorption in the cochlea in order to
      better understand factors that may influence cisplatin-induced ototoxicity. The
      effect of reduced cochlear blood flow on the ototoxic action of cisplatin was
      studied in guinea pigs. Before cisplatin administration the cochlear vasculature
      in each animal was unilaterally pre-constricted, by the application of 2%
      epinephrine to the round window. A 20-30% reduction in cochlear blood flow,
      assessed by laser Doppler flowmetry, was maintained before and after intravenous
      infusion of 0.1% cisplatin. Cisplatin infusion affected cochlear blood flow but
      not vessel conductivity. The cochlear blood flow decrease, maintained by local
      epinephrine application to the round window during cisplatin infusion, did not
      alter the cisplatin-induced hearing loss. In addition, the concentration of free
      cisplatin in scala tympani perilymph did not differ between epinephrine-treated
      and non-treated ears. Our results indicate that cisplatin transport into the
      cochlea is not an energy-dependent process in the lateral wall vasculature.

PMID- 9039483
TI  - Similar pharmacokinetics and differential ototoxicity after administration with
      cisplatin and transplatin in guinea pigs.
AB  - Transplatin is a transisomer of cisplatin. Although cisplatin exhibits strong
      ototoxicity, there is no report concerning the ototoxicity of transplatin. To
      evaluate differences in pharmacokinetics and ototoxicity, cisplatin (7.5 mg/kg)
      and transplatin (30 mg/kg) were administered to guinea pigs twice at an interval
      of 5 days. The N1 threshold of the compound action potential was significantly
      elevated after administration of cisplatin. Cochleogram of the cisplatin-treated
      group showed severe losses of outer hair cells essentially at the basal and
      second turns. Transplatin, however, did not induce any detectable functional or
      morphological changes. Furthermore, blood urea nitrogen and creatinine levels in
      serum were not elevated after administration of transplatin, whereas cisplatin
      showed strong nephrotoxicity. The serum and perilymphatic concentrations of
      platinum up to 24 h after administering an equimolar dose of cis- or transplatin
      (7.5 mg/kg) were almost similar. As has been reported by many investigators,
      transplatin has no anti-tumor activity because stereochemical limitations
      preclude transplatin from forming intra- and interstrand closs-links with nuclear
      or mitochondrial DNA. From these results, it was concluded that the
      stereochemical structure of the platinum compound and steric interaction with
      target molecules such as mitochondrial DNA in the cochlear outer hair cells might
      be important to the ototoxic mechanism of platinum compounds.

PMID- 9039484
TI  - Physiological and anatomical study of click-sensitive primary vestibular
      afferents in the guinea pig.
AB  - We studied the sensitivity of primary vestibular afferents in anaesthetised
      guinea pigs to clicks. These vestibular neurons were also tested by their
      response to pitch and roll tilts and yaw-axis angular acceleration. The click
      intensity was referred to the threshold for evoking the auditory brainstem
      responses. Recording sites in the vestibular nerve were confirmed histologically
      using iontophoretic injection of FCF green dye. To confirm the site of
      labyrinthine origin of the click-sensitive neurons, we used retrograde tracing
      with biocytin. In all, 647 out of 2354 neurons in the vestibular nerves of 51
      guinea pigs were activated by clicks. Most were irregularly discharging primary
      neurons, but some were regularly discharging. We studied responses to vestibular
      stimuli in 188 click-sensitive neurons. Of these, 86% responded to pitch and/or
      roll tilt, but none responded to yaw angular acceleration. Conversely we also
      recorded vestibular neurons which did not respond to clicks. None of 300 neurons
      sensitive to yaw angular acceleration were responsive to 80-90 dB SL clicks (0 dB
      SL = threshold for auditory brainstem response to clicks). The latencies of click
      evoked action potentials of neurons in the vestibular nerve were very short (mean
      +/- SD = 0.82 +/- 0.22 ms). Changing click polarity caused a heterogeneous
      pattern of latency change. Thresholds for evoking spikes in primary vestibular
      neurons were high (62.0 +/- 12.2 dB SL, range 30-90 dB, n = 371). Retrograde
      tracing of the origin of the click-sensitive afferents using extracellular
      biocytin showed that most neurons originated in the medial (striola area) of the
      saccular macula.

PMID- 9039486
TI  - Anti-glomerular basement membrane antibody-induced inflammation in rat cochlear
      plexus.
AB  - Autoimmune inner ear diseases have been recognized recently, but the mechanism of
      hearing loss is still unclear. This study was aimed to induce immunological
      inflammation in cochlea to establish a model and to examine an effect of
      prednisolone on the induction. Lewis rats were immunized with normal rabbit IgG
      in complete Freund's adjuvant, and then injected intravenously with rabbit anti
      rat glomerular basement membrane (GBM) antibody twice (anti-GBM Ab group). The
      binding of anti-GBM antibody and inflammatory cell infiltration in the cochlear
      plexus were investigated using immunofluorescence microscopy. Immunofluorescence
      microscopic examination revealed specific binding of anti-GBM Ab to basement
      membrane of capillaries in the cochlear plexus. Compared to normal rats injected
      with saline, larger numbers of infiltrated CD4-positive T cells (p < 0.01) and
      monocytes/macrophages (p < 0.01) were observed. Furthermore, prednisolone
      suppressed the infiltration of CD4-positive cells (p < 0.05) and
      monocytes/macrophages (p < 0.01). These results suggest that an inflammatory
      reaction was induced by binding of anti-basement membrane antibody to cochlear
      capillaries in inner ear and that this inflammation in cochlea could be reduced
      by prednisolone.

PMID- 9039485
TI  - Effect of Pseudomonas aeruginosa exotoxin A on inner ear function.
AB  - Electrophysiological changes were studied in the albino rat following
      instillation of Pseudomonas aeruginosa exotoxin A into the middle ear cavity
      through the tympanic membrane. Hearing threshold was measured by a burst
      elicited, frequency-specific auditory brainstem response (ABR) technique prior to
      exposure, then 24 and 48 h, 5 days, 2 and 4 weeks after the toxin instillation. A
      single dose (1 microgram/20 microliters) of Pseudomonas aeruginosa exotoxin A
      raised the ABR threshold over the whole frequency range, by 5-25 dB, particularly
      in the high tones. All threshold shifts were of combined conductive and cochlear
      type, reversible, with deterioration starting at 24-48 h and recovery at 2-4
      weeks. Effusion of serous fluid occurred at 24 or 48 h, resulting in conductive
      hearing loss. Latency/intensity curves revealed a cochlear component in addition
      to conductive hearing loss. Morphological examination by SEM showed slight and
      inconsistent derangement of OHCs. It is concluded that Pseudomonas aeruginosa
      exotoxin A causes middle ear inflammation, facilitating penetration to the inner
      ear and that this toxin also reversibly affects cochlear function.

PMID- 9039487
TI  - Otitis-prone children and controls: a study of possible predisposing factors. 1.
      Heredity, family background and perinatal period.
AB  - In a retrospective study of 179 otitis-prone children and 305 controls, various
      possible predisposing factors for acute otitis media (AOM) were compared. The
      children were matched for age and sex. There were 61% boys and 39% girls in the
      otitis-prone group and 58% boys and 42% girls among the controls. Eighty-eight
      (49%) of the otitis-prone children experienced > or = 11 episodes of AOM and 162
      (53%) of the controls had none or at the most one episode of AOM. There were no
      differences between the groups concerning dwelling districts, the size of family,
      number of siblings or the education and occupation of the parents. In the otitis
      prone group there were more fathers who had been otitis-prone as children. This
      was not seen for the mothers when comparing all the children, but was seen when
      comparing the most otitis-prone (> or = 11 AOM) with the controls (0-1 AOM). The
      otitis-prone children more often had siblings who were otitis-prone compared with
      the controls. There were no differences between the two groups regarding
      pregnancy, birthweight or duration of breast-feeding. Thus, male gender and
      heredity for middle-ear problems appeared to be of importance for otitis
      proneness.

PMID- 9039488
TI  - Hearing results in otosclerosis surgery after partial stapedectomy, total
      stapedectomy and stapedotomy.
AB  - Hearing results in a consecutive series of 407 patients with otosclerosis
      undergoing primary stapes surgery were analysed (437 operated ears). Partial
      stapedectomy was performed in 70 ears (16%), total stapedectomy in 205 ears
      (47%), in both groups using the House steel wire prosthesis on fascia in the oval
      window. The remaining 162 ears (37%) underwent stapedotomy using the Fisch 0.4 mm
      teflon-platinum piston. No case of cochlear loss (> 15 dB) occurred in the total
      series. The comparison between the three groups one year postoperatively showed
      that the air-bone gap was smaller for partial and total stapedectomy for all
      frequencies except 4 kHz. The air-bone gap was calculated as the difference
      between the preoperative bone conduction and the postoperative air conduction
      thresholds. Partial and total stapedectomy also showed larger improvements of
      bone conduction thresholds compared with stapedotomy for all frequencies but 4
      kHz. At the 3-year follow-up, the hearing gain for all frequencies (250-8000 Hz)
      was larger for partial and total stapedectomy. Yet, when comparing the decline of
      hearing from 1 to 3 year postoperatively, the hearing gain achieved with partial
      and total stapedectomy seemed to deteriorate at a higher rate, which was
      considered to be caused by impaired sensorineural function. Our results show that
      in the short-term perspective partial or total stapedectomy can still compete for
      better hearing results even at higher frequencies, but stapedotomy seems to yield
      more stable hearing results over time and should therefore be considered as the
      method of choice.

PMID- 9039489
TI  - Auditory epidermal cell migration. VII. Antigen expression of proliferating cell
      nuclear antigens, PCNA and Ki-67 in human tympanic membrane and external auditory
      canal.
AB  - A location of proliferating cells was investigated in eight human normal tympanic
      membranes (TMs) and external auditory canals (EACs) by an immunohistochemical
      method using two different types of antibodies for nuclear antigens in
      proliferating cells: anti-PCNA monoclonal antibody, and anti-Ki-67 polyclonal
      antibody. Four specimens prepared for cryostat sections were immunostained by
      both antibodies. Another four were fixed in 4% formaldehyde solution, embedded in
      paraffin wax and were reacted only with anti-PCNA antibodies. The expression
      pattern of Ki-67 was basically the same as of PCNA. In the pars tensa (PT),
      immunoreactivities were expressed in the nuclei of basal layer cells and cells
      just overlying the basal layer of epidermis both in the handle of the malleus
      (HM) and annular regions. In the intermediate region of the PT, no
      immunoreactivity was found basically, apart from a few labelled cells observed in
      the upper-third of the superior quadrant. In the pars flaccida (PF) and in both
      the osseous and cartilaginous regions of the EAC, positive cells were also
      situated in the basal layer and the deeper aspect of the suprabasal layers
      without any specific distributing pattern. It was certified that the generation
      centre of epidermal cells (keratinocytes) in the PT was located in both the HM
      and annular regions, and that stem cells in the PF and the EAC were uniformly
      scattered in the basal layer and the deeper aspect of the spinous layer.
      According to these findings, the migratory patterns of auditory epidermal cells
      in the human TM and EAC were discussed.

PMID- 9039490
TI  - The effect of antibiotic treatment on the release of endotoxin during nontypable
      Haemophilus influenzae-induced otitis media in the chinchilla.
AB  - The gram negative bacteria, nontypable Haemophilus influenzae (NTHi) was used to
      induce otitis media in a total of 18 chinchillas. Three days post-inoculation,
      three cohorts of 6 chinchillas each were treated daily for four days with either
      ceftriaxone, chloramphenicol, or diluent without antibiotics. Middle ear fluid
      (MEF) was obtained daily, assayed for endotoxin content by means of the
      chromogenic limulus amebocyte lysate assay, and concentration of the NTHi/mL MEF
      determined by standard plate count. The endotoxin concentration per mL MEF from
      both the antibiotic treated cohorts decreased during the observation period, but
      increased in the MEF of the untreated control group. The data indicate that,
      unlike the dramatic increase in endotoxin concentration, after antibiotic
      treatment in the cerebrospinal fluid (CSF) during experimental Haemophilus
      influenzae-induced meningitis, there is no demonstrable sustained release of
      endotoxin in the middle ear subsequent to antibiotic treatment during
      experimental otitis media.

PMID- 9039491
TI  - Nitric oxide (NO) production in the upper airways is decreased in chronic
      sinusitis.
AB  - The nasal concentration of nitric oxide (NO) was measured by chemiluminescence in
      healthy volunteers 3-68 years of age, and in patients suffering from common cold
      and chronic sinusitis. The concentration of NO in healthy subjects, 233.2 +/-
      66.8 ppb (mean +/- SD), was found to be relatively independent of age and body
      size. The measured levels of NO did not differ between healthy volunteers and
      common cold patients, but they were significantly lower in patients suffering
      from chronic sinusitis, 96.4 +/- 72.8 ppb. As NO is a regulator of mucociliary
      activity and has bacteriostatic and antiviral effects, the decreased
      concentration of NO in patients suffering from sinusitis suggests that lack of NO
      may contribute to the pathogenesis of this disease. The importance of NO for the
      mucociliary system was emphasized by the finding that the 2 patients with the
      lowest nasal concentration of NO were found to manifest functional and
      morphological changes of the mucociliary system that are typical of acquired
      mucociliary dysfunction.

PMID- 9039492
TI  - The embryonic development of the human ethmoid labyrinth from 8-40 weeks.
AB  - The embryonic development of the human ethmoid labyrinth was studied in 24 fetal
      heads aged between 8 and 40 weeks of gestation under light microscopy. The
      uncinate process was identifiable at 8 weeks of gestation on the laterosuperior
      portion of the inferior turbinate; however, at this stage of development, the
      ethmoid bulla was not apparent. The ethmoid bulla developed on the lateral wall
      of the middle meatus by 12 weeks of gestation. By 14 weeks, the primordial
      ethmoid infundibulum and primordial maxillary sinus were seen developing between
      the uncinate process and the ethmoid bulla. It was obvious that the anterior and
      middle ethmoid cells developed from the ethmoid bulla. By 22 weeks of gestation,
      the first cell of the anterior ethmoid group was evident in the anterior-inferior
      portion of the ethmoid bulla. By 23 weeks of gestation, the first cell of the
      middle ethmoid group was visible in the superior portion of the ethmoid bulla.
      Pneumatization of the middle turbinate occurred as part of normal development of
      the ethmoid labyrinth. By 32 weeks of gestation, the ostium for the development
      of the middle turbinate cell was seen in the superior-interior portion of the
      middle turbinate. These observations provide new insight into the development of
      the ethmoid labyrinth and have important implications for the understanding of
      normal anatomy and developmental variants of the ethmoid labyrinth.

PMID- 9039493
TI  - Production and gene expression of IL-8-like cytokine GRO/CINC-1 in rat nasal
      mucosa.
AB  - Growth-regulated gene product/cytokine-induced neutrophil chemoattractant
      (GRO/CINC)-1 is a rat chemokine with structural and functional homology to human
      IL-8. Chemokines are a family of cytokines whose participation in nasal
      inflammation in vivo remains to be established. Using ELISA and RT-PCR, we
      investigated the production and gene expression of GRO/CINC-1 in rat nasal lavage
      and mucosa in vivo. GRO/CINC-1 in nasal lavage was produced by stimulation of
      LPS, ConA and IL1-beta. GRO/CINC-1 showed time- and dose-dependent production
      under all stimulants, but was more slowly induced by IL-1 beta. The steady-peak
      of the GRO/CINC-1 production remained at 3 h with LPS or ConA exposure, whereas
      it lasted 4 h or more after IL-1 beta exposure. At the time of peak production of
      GRO/CINC-1, we found that mRNA for the GRO/CINC-1 was induced in the nasal
      mucosa. The mRNA of the related inflammatory cytokines TNF-alpha and IFN-gamma
      were also expressed in nasal mucosa with stimulation of these reagents. Thus,
      this study revealed that exposure to bacterial endotoxin, mitogenic reagent and
      also IL-1 beta induced the production and gene expression of the neutrophil
      chemoattractant GRO/CINC-1 in rat nasal mucosa in vivo. This investigation of the
      characteristics of IL-8 family in nasal mucosa using rat models has extended the
      functional concept of cytokines in the inflammatory condition of nasal cavity in
      humans.

PMID- 9039494
TI  - Endolymph flow.

PMID- 9039495
TI  - The treatment of atrial fibrillation: pharmacologic and nonpharmacologic
      strategies.

PMID- 9039496
TI  - Nucleotide sequence of the psbP gene encoding precursor of 23-kDa polypeptide of
      oxygen-evolving complex in Arabidopsis thaliana and its expression in the wild
      type and a constitutively photomorphogenic mutant.
AB  - The psbP gene encoding the precursor of 23-kDa polypeptide of the oxygen-evolving
      complex of photosystem II has been isolated from Arabidopsis thaliana genomic
      library and sequenced. The gene harbors three introns and encodes a mature
      polypeptide of 186 amino acid residues and a transit peptide of 77 amino acid
      residues. The deduced molecular mass of the mature polypeptide is 23.5-kDa and it
      contains 22.6% charged amino acid residues which may contribute to the
      hydrophilic nature of the protein. The transcript encoded by psbP gene of
      Arabidopsis is approximately 1.3-kb long. In wild-type Arabidopsis seedlings, its
      expression is organ-specific and is regulated by endogenous developmental cues,
      light and sucrose. In a constitutively photomorphogenic mutant of Arabidopsis,
      designated as pho1, the psbP gene is partly derepressed in young, dark-grown
      seedlings, resulting in a slightly higher level of the transcript. Additionally,
      the pho1 mutant shows slow accumulation of psbP transcript upon illumination of
      young, dark-grown seedlings. However, the derepression is not markedly displayed
      on dark-adaptation of pho1 plants grown in continuous light. These studies,
      therefore, define the activity of at least one cellular effector involved in
      regulation of psbP expression.

PMID- 9039497
TI  - Genomic recombination of the mitochondrial atp6 gene in Arabidopsis thaliana at
      the protein processing site creates two different presequences.
AB  - In the mitochondrial genome of the flowering plant Arabidopsis thaliana the atp6
      open reading frame is located on the border of one of the repeats resulting in
      two copies with different presequence extensions. The two presequences of 135 and
      97 amino acids respectively show no similarity to each other, while the mature
      protein sequences are identical. Both preproteins are most likely synthesized in
      Arabidopsis mitochondria from promoter elements upstream of each copy. The
      presence of two arrangements in the mitochondrial genome of fertile Arabidopsis
      plants suggests this recombination to be unrelated to a cytoplasmic male sterile
      phenotype. This recombination precisely at the mature protein terminus is
      reminiscent of the domain shuffling model in protein evolution.

PMID- 9039498
TI  - Physical mapping of rice chromosome 1 with yeast artificial chromosomes (YACs).
AB  - We have constructed a physical map of rice chromosome 1 using yeast artificial
      chromosomes (YACs). A YAC library of 350 kb average insert size, covering about 6
      rice haploid genome equivalents, was screened using 182 DNA markers which we had
      previously located on chromosome 1, by colony hybridization and polymerase chain
      reaction (PCR) amplification. One hundred and sixty-two DNA markers identified at
      least one YAC each carrying one, two or more marker sequences, for a total of 476
      clones. Of these identified YACs, 284 were located in their original positions on
      chromosome 1. These 284 YACs defined 69 YAC contigs or islands which are
      estimated to cover more than 60% of the total chromosome length. The use of
      mapped DNA markers in constructing a physical map facilitates the integration of
      genetic and physical maps, as well as fine ordering of the DNA markers,
      especially at sites where the markers are clustered tightly on the genetic map.
      Our high density molecular map has been proven, by chromosome landing with YACs
      using mapped DNA markers, to cover more than half of the entire length of
      chromosome 1. The remaining 192 YACs were selected by other copies of DNA markers
      that mapped on chromosome 1. This description of the YAC contigs formed on
      chromosome 1 constitutes the second report of rice physical mapping, following
      that for chromosome 6.

PMID- 9039499
TI  - Construction of YAC contigs on rice chromosome 5.
AB  - A physical map of rice chromosome 5 was constructed with yeast artificial
      chromosome (YAC) clones along a high-resolution molecular linkage map carrying
      118 DNA markers distributed over 123.7 cM of genomic DNA. YAC clones have been
      identified by colony and Southern hybridization for 105 restriction fragment
      length polymorphism (RFLP) markers and by polymerase chain reaction (PCR)
      screening for 8 sequence-tagged site (STS) markers and 5 randomly amplified
      polymorphic DNA (RAPD) markers. Of 458 YACs, 235 individual YACs with an average
      insert length of 350 kb were selected and ordered on chromosome 5 from the YAC
      library. Forty-eight contigs covering nearly 21 Mb were formed on the chromosome
      5; the longest one was 6 cM and covered 1.5 Mb. The length covered with YAC
      clones corresponded to 62% of the total length, of chromosome 5. There were many
      multicopy sequences of expressed genes on chromosome 5. The distribution of many
      copies of these expressed gene sequences was determined by YAC Southern
      hybridization and is discussed. A physical map with these characteristics
      provides a powerful tool for elucidation of genome structure and extraction of
      useful genetic information in rice.

PMID- 9039500
TI  - Characterization and mapping of cDNA encoding aspartate aminotransferase in rice,
      Oryza sativa L.
AB  - Fifteen cDNA clones, putatively identified as encoding aspartate aminotransferase
      (AST, EC 2.6.1.1.), were isolated and partially sequenced. Together with six
      previously isolated clones putatively identified to encode ASTs (Sasaki, et al.
      1994, Plant Journal 6, 615-624), their sequences were characterized and
      classified into 4 cDNA species. Two of the isolated clones, C60213 and C2079,
      were full-length cDNAs, and their complete nucleotide sequences were determined.
      C60213 was 1612 bp long and its deduced amino acid sequence showed 88% homology
      with that of Panicum miliaceum L. mitochondrial AST. The C60213-encoded protein
      had an N-terminal amino acid sequence that was characteristic of a mitochondrial
      transit peptide. On the other hand, C2079 was 1546 bp long and had 91% amino acid
      sequence homology with P. miliaceum L. cytosolic AST but lacked in the transit
      peptide sequence. The homologies of nucleotide sequences and deduced amino acid
      sequences of C2079 and C60213 were 54% and 52%, respectively. C2079 and C60213
      were mapped on chromosomes 1 and 6, respectively, by restriction fragment length
      polymorphism linkage analysis. Northern blot analysis using C2079 as a probe
      revealed much higher transcript levels in callus and root than in green and
      etiolated shoots, suggesting tissue-specific variations of AST gene expression.

PMID- 9039501
TI  - Identification and cloning of neuroblastoma-specific and nerve tissue-specific
      genes through compiled expression profiles.
AB  - An expression profile of active genes in a human neuroblastoma cell line CHP134
      was obtained by collecting 1222 partial sequences from a 3'-directed cDNA library
      representing a non-biased mRNA population. By comparing this expression profile
      with the compiled profiles of multiple tissues, several novel gene transcripts
      that appeared only in the profile of the neuroblastoma cell line were identified.
      Further analyses by Northern blotting revealed two specific cDNA clones that are
      expressed in most of the human neuroblastomas examined, and three that are in
      some of the human neuroblastoma cell lines as well as in the adult human brain.
      Full-size cDNAs were cloned using these five partial cDNA sequences as probes and
      sequenced. A database search revealed that they are all novel and unique
      sequences: one sharing some amino acid sequence similarities with a cytoskeletal
      protein, two clones likely to be transcriptional factors, a clone that has
      characteristic potassium channel properties, and a clone that is non-homologous
      to any one of the known proteins. Thus, we argue that the collection of 3'
      directed cDNA sequences in combination with the compiled expression profiles of
      active genes in multiple tissues is a powerful tool for discovering novel genes
      that are specifically expressed in a given cell or tissue, in this case
      neuroblastomas and/or nerve tissue.

PMID- 9039502
TI  - Prediction of the coding sequences of unidentified human genes. VI. The coding
      sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones
      from cell line KG-1 and brain.
AB  - In this series of projects of sequencing human cDNA clones which correspond to
      relatively long and nearly full-length transcripts, we newly determined the
      sequences of 80 clones, and predicted the coding sequences of the corresponding
      genes, named KIAA0201 to KIAA0280. Among the sequenced clones, 68 were obtained
      from human immature myeloid cell line KG-1 and 12 from human brain. The average
      size of the clones was 5.3 kb, and that of distinct ORFs in clones was 2.8 kb,
      corresponding to a protein of approximately 100 kDa. Computer search against the
      public databases indicated that the sequences of 22 genes were unrelated to any
      reported genes, while the remaining 58 genes carried sequences which show some
      similarities to known genes. Protein motifs that matched those in the PROSITE
      motif database were found in 25 genes and significant transmembrane domains were
      identified in 30 genes. Among the known genes to which significant similarity was
      shown, the genes that play key roles in regulation of developmental stages,
      apoptosis and cell-to-cell interaction were included. Taking into account of both
      the search data on sequence similarity and protein motifs, at least seven genes
      were considered to be related to transcriptional regulation and six genes to
      signal transduction. When the expression profiles of the cDNA clones were
      examined with different human tissues, about half of the clones from brain (5 of
      11) showed significant tissue-specificity, while approximately 80% of the genes
      from KG-1 were expressed ubiquitously.

PMID- 9039503
TI  - Nucleotide sequence of a 28-kb mouse genomic region comprising the imprinted Igf2
      gene.
AB  - The mouse insulin-like growth factor II gene (Igf2) is physically linked to the
      insulin II gene (Ins2) and both are subject to tissue-specific genomic
      imprinting. The paternal-specific expression of Igf2 has been associated with
      hypermethylation of some CpG sites in the 5' flanking region and in the body of
      the gene. As a first step in analyzing the structural features of this imprinted
      locus, we here report the complete nucleotide sequence of Igf2, including all
      introns and the intergenic region adjacent to Ins2. This 28-kb segment of mouse
      chromosome 7 exhibits 80% overall identity with the corresponding rat sequence
      and has a high GC content of 52%. In addition to the known CpG island within the
      second Igf2 promoter, another island was identified approximately 2 kb 5' to the
      first exon. Other features of this locus include a 35-fold tandem repeat of an 11
      bp sequence that overlaps Igf2 pseudo-exon 2, and a B2 repeat element in the
      intergenic region between Ins2 and Igf2. The GC-richness and the presence of CpG
      islands associated with tandem repeats are common features of imprinted genes and
      thus may play a role in the imprinting mechanism.

PMID- 9039504
TI  - Isolation and analysis of a novel gene, HXC-26, adjacent to the rab GDP
      dissociation inhibitor gene located at human chromosome Xq28 region.
AB  - We screened potential promoter regions from NotI-linking cosmid clones mapped on
      human chromosome Xq28 region with our constructed trapping vector and isolated
      six fragments containing transcription activity. Using one of the obtained
      fragments as a probe, a novel gene was isolated by screening a human skeletal
      muscle cDNA library. The isolated cDNA, termed HXC-26, contained an open reading
      frame of 975 nucleotides encoding 325 amino acids (38,848 Da). The HXC-26 gene
      was composed of 13 exons that span approximately 8 kb. Several potential GC boxes
      were found in the putative promoter region, but no typical TATA box. The HXC-26
      gene associated with a CpG island was located adjacent to the rab GDP
      dissociation inhibitor (GDI) gene.

PMID- 9039506
TI  - Neonatal seizures.
AB  - The newborn brain is particularly vulnerable to seizures which are associated
      with poor neurodevelopmental outcome. The clinical manifestations of seizures in
      infants differ from those seen in older children and adults. The problem of
      electro-clinical dissociation, where there is no temporal correspondence between
      electrical paroxysms and repetitive stereotyped motor phenomena, is common in the
      newborn. There is at present very little information on which clinicians can base
      a rational decision about treatment which is often ineffective and does not alter
      neurodevelopmental outcome. This review summarizes current knowledge regarding
      investigation, treatment and prognosis of neonatal seizures.

PMID- 9039507
TI  - Should frusemide be prescribed after packed red cell transfusions in the newborn?

PMID- 9039508
TI  - Corticosteroid treatment of erythema multiforme major (Stevens-Johnson syndrome)
      in children.
AB  - The effectiveness of systemic corticosteroids in erythema multiforme major (EMM)
      is controversial. We therefore evaluated the efficacy of corticosteroids in the
      treatment of EMM in a prospective study of 16 children with EMM admitted to our
      department within 3 days from the onset of rash. Ten patients (group A) received
      bolus infusions of methylprednisolone (4 mg/kg/day) while six had only supportive
      treatment (group B). The early use of corticosteroids compared to supportive
      treatment resulted in: (1) significant reduction of the period of fever (4.0 +/-
      1.9 vs 9.5 +/- 4.2 days P = 0.01); (2) reduction of the period of acute eruption
      (7.0 +/- 3.3 versus 9.8 +/- 3.0 days P = 0.08); and (3) milder signs of
      prostration. Complications were minimal in both groups. CONCLUSION: The early and
      short course of corticosteroids favourably influences the course of erythema
      multiforme major in children.

PMID- 9039509
TI  - A thyroxine dosage of 8 micrograms/kg per day is appropriate for the initial
      treatment of the majority of infants with congenital hypothyroidism.
AB  - The adequate L-thyroxine dosage for the initial treatment of infants with
      congenital hypothyroidism is a subject of controversy. Some recommend higher
      dosages (> 10 micrograms/kg/day) to ensure adequate levels, while others advocate
      lower dosages to permit normalisation of thyroid status. The aim of this study
      was to evaluate the results of a treatment strategy using an initial dosage of
      7.5-8.0 micrograms/kg per day, TSH measurements being taken at 15 and 30 days of
      treatment. Fifty one newborns infants with primary congenital hypothyroidism
      detected by neonatal screening were treated with the same therapeutic strategy. A
      mean L-thyroxine dosage of 7.9 micrograms/kg per day at the onset of treatment
      and 6.6 micrograms/kg/d at 2 months, normalised the FT4 and FT3 levels at 15 days
      in 100% and TSH levels at 2 months in 90% of cases. Many patients showed elevated
      levels of FT4 and a systematic higher initial dosage could expose many infants to
      a dangerous hyperthyroidism. Patients with abnormal TSH levels at 2 months
      already had higher TSH levels in the first 8 weeks of life and, despite higher L
      thyroxine dosage, also exhibited lower FT4 and FT3 levels. These patients who
      needed an early increase in dosage had already shown a more profound ante and
      neonatal hypothyroidism. This subgroup of patients require a higher dosage of
      thyroxine and early assessment of FT4, FT3 and TSH levels are required for
      optimum dosage choice. CONCLUSION: Even though a subgroup of patients may require
      a higher dosage of L-thyroxine, an initial dosage of 7.5-8.0 micrograms/kg per
      day, with an early assessment of FT4, FT3, and TSH levels, is adequate for the
      treatment of the majority of infants with congenital hypothyroidism.

PMID- 9039510
TI  - The influence of growth hormone monotherapy and growth hormone in combination
      with oxandrolone or testosterone on thyroxid hormone parameters and thyroxine
      binding globulin in patients with Ullrich-Turner syndrome.
AB  - Administration of human growth hormone (GH) has yielded conflicting results
      concerning its role on thyroid function in patients with Ullrich-Turner syndrome.
      Therefore, we investigated the course of thyroid hormone parameters and thyroxin
      binding globulin in relation to GH therapy, IGF-I and additional oxandrolone-(Ox)
      or testosterone (T) treatment in 20 patients with Ullrich-Turner syndrome. During
      the 1st year the patients received only GH. There was no change in T4, fT4, and
      TSH levels, T3 increased significantly (P < 0.01) after 6 and 12 months,
      resulting in a higher T3/T4 ratio. TBG (P < 0.05) and IGF-I (P < 0.01) increased
      after 6 months and remained elevated at 12 months. A significant positive
      correlation was found between the change of T4 and TBG after 6 months (r = 0.47,
      P < 0.05) and after 12 months (r = 0.69, P < 0.005). Thirteen patients were
      further investigated after addition of an anabolic compound; 7 received Ox
      (0.0625 mg/kg/day po) and 6 low dose T (5 mg i.m. every 14 days). Chronological
      age was comparable in these groups (10.7 +/- 2.7 vs 10.7 +/- 3.6 years). After 6
      months of combination therapy with Ox, T4, T3 and TSH decreased. As T4 and T3
      showed a parallel decrease the T3/T4 ratio remained elevated. TBG declined after
      6 and 12 months (P < 0.05), while IGF-I showed a further increment (P < 0.05).
      There was no correlation between the changes in T4 and IGF-I, TSH and TBG,
      respectively. In the T-treated group only IGF-I increased (P < 0.05) to the same
      extent as in the Ox-treated patients, whereas the thyroid parameters did not
      change. CONCLUSION: The observed changes in thyroid hormone and TBG levels in the
      Ox group were not mediated by GH or IGF-I. The Ox-induced TBG decrease might be
      linked to altered pancreatic functions regulating carbohydrate metabolism.

PMID- 9039511
TI  - The relation between gastro-oesophageal reflux, sleeping-position and sudden
      infant death and its impact on positional therapy.
AB  - Many infants do regurgitate. The recommended therapeutic approach starts with
      postural and dietary measures, followed by antacids and prokinetics. However, the
      recent findings regarding the increased risk for sudden infant death (SID) in the
      prone sleeping position challenge the current recommendations. Management of
      regurgitation should in the first place aim at reducing parental anxiety.
      Postural treatment favouring the prone-elevated (30 degrees) position is no
      longer recommended as a first line treatment of regurgitation, despite its
      efficacy, because of the unexplained association of SID with the flat prone
      sleeping position. Favouring the prone elevated position would result in an
      increased parental anxiousness. CONCLUSION: Positional treatment can only be
      recommended in children beyond the age of SID risk, or as an adjuvant therapy in
      cases resistant to reassurance, thickeners and prokinetics and in whom other
      diagnostic possibilities (infection, etc.) are considered rejected.

PMID- 9039512
TI  - Malignant fibrous histiocytoma of the lung in a child. An unusual neoplasm that
      can mimick inflammatory pseudotumour.
AB  - We describe a 12-year-old patient with a primary pulmonary mass in the left upper
      lung. The diagnosis of inflammatory pseudotumour was suspected preoperatively.
      After pathological examination and complete clinical evaluation, a diagnosis of
      malignant primary pulmonary fibrous histiocytoma was established. This is a very
      uncommon primary neoplasm of the lung and to our knowledge only five paediatric
      cases have been reported. Because of the rarity of these sarcomas and
      histological similarities to benign inflammatory pseudotumour, care must be taken
      to avoid confusion between the two disorders particularly in intra-operative
      frozen sections. CONCLUSION: Primary malignant fibrous histiocytoma of the lung
      is an uncommon tumour that should be considered in the differential diagnosis of
      pulmonary neoplasms of childhood. The histological diagnosis can be difficult due
      to the similarities with inflammatory pseudotumour.

PMID- 9039513
TI  - Food intolerance (food hypersensitivity) and chronic complaints in children: the
      parents' perception.
AB  - The aim of the study was to assess the prevalence of food intolerance (FI) in
      Dutch 5- and 6-year-old children and its association with chronic ailments with a
      survey among parents by questionnaire. Based on parents' perception the
      prevalence of "probable" FI was 3.8%. FI was associated with asthma, wheezing,
      eczema, hay fever, chronic rhinitis, hives, chronic diarrhoea and hyperactive
      behaviour. The Dutch research results are commensurate with the findings of a
      study carried out in the U.K. Parents frequently associate FI with eczema, hives,
      chronic diarrhoea and hyperactivity. The association with FI remains for asthma,
      wheezing, chronic rhinitis, hay fever, chronic diarrhoea and hyperactive
      behaviour even after adjustment for this information bias. CONCLUSION: Many
      parents are not aware that chronic ailments in their child may be caused by FI.
      The associations of FI and chronic complaints are strong enough to justify the
      discussion with parents during the client contacts by school physicians, in order
      to assess the advantages of consulting a paediatrician or allergologist.

PMID- 9039514
TI  - Development of systemic lupus erythematosus in a patient with selective complete
      C1q deficiency.
AB  - A 7-year-old male with recurrent erythematous and desquamated skin lesions and
      respiratory infections was diagnosed as selective complete C1q deficiency
      following detailed studies of the complement system. His asymptomatic sister also
      had selective complete C1q deficiency. During a follow up period of 3 years, his
      skin lesions persisted, he suffered from recurrent bronchopneumonias and
      glomerulonephritis developed. Renal function deteriorated with the appearance of
      anti-DNA antibodies. Renal biopsy was consistent with systemic lupus
      erythematosus. The patient was treated with immunosuppressive drugs, but died of
      renal failure. It is postulated that in this patient defective clearance of
      antigen-antibody complexes by the reticulo-endothelial system resulted in
      progressive renal disease as observed in other complement deficiencies. A
      retrospective molecular study disclosed a point mutation in the ClqA chain gene
      in a heterozygous state in parents and two siblings; in a homozygous state in the
      asymptomatic sister. The reason why some individuals with this defect are
      asymptomatic is not known at present. Diagnosis of heterozygotes by molecular
      studies is extremely important to give genetic counselling to the family.
      CONCLUSION: Patients with recurrent infections, erythematous desquamative skin
      lesions, malar rash and oral mucosal involvement should be screened for
      complement C1q deficiency.

PMID- 9039515
TI  - Altered follicle stimulating hormone isoforms in female galactosaemia patients.
AB  - Many women affected with galactosaemia suffer from ovarian dysfunction and have
      elevated serum levels of follicle stimulating hormone (FSH). We have analysed FSH
      glycoprotein isoforms from four galactosaemic and five healthy women. Besides the
      commonly found FSH species with a median isoelectric point (pI) of 4-5, the sera
      of the female galactosaemic patients contained qualitatively abnormal FSH
      isoforms with a pI close to neutral (6.4-7.0). The generally reduced
      galactosylation in patient samples was confirmed because sera of galactosaemic
      patients could incorporate 1.7 times more UDP-(14C)galactose than did healthy
      subjects. CONCLUSION: Our data indicate that the terminal disaccharides of FSH (a
      glycoprotein), galactose and sialic acid were partially deficient in three
      galactosaemic female patients with no galactose-1-phosphate uridyl transferase
      (GALT) activity in red cells. However, from a female patient with a residual GALT
      activity (a mild form of galactosaemia), no distinctive deficiency was observed.
      This again suggest an importance of GALT in retaining a correct FSH structure.
      Therefore the abundance of neutral FSH isoforms, which was described to have a
      higher binding affinity to its receptor and no capacity to activate cyclic
      adenosine mono-phosphate (cAMP), may cause a hormonal dysfunction in classical
      galactosaemia.

PMID- 9039516
TI  - Marked changes of lipid levels during puberty in a patient with lipoprotein
      lipase deficiency.
AB  - Clinical and biochemical characteristics of a female patient with familial
      lipoprotein lipase deficiency have been followed in short intervals before and
      during puberty. The proband is compound heterozygote for two missense mutations
      in the lipoprotein lipase gene. One mutation occurs in codon 250 (Asp250-->Asn),
      the other is in codon 410 (Glu410-->Lys). The residual lipoprotein lipase
      activity in the proband is less than 10% of controls. Before puberty the proband
      usually presented with moderate isolated hypertriglyceridaemia. During the
      initial phase of puberty a dramatic increase in the plasma concentration of both
      cholesterol and triglycerides was observed. During the second half of puberty a
      reduction of cholesterol but not of triglycerides was noticed. CONCLUSION: These
      findings show that the phenotypic expression of familial chylomicronaemia can be
      modified to a large extent by hormones. Furthermore they demonstrate the need for
      a closer clinical observation of type I patients during puberty.

PMID- 9039517
TI  - Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral
      dose schedules of vitamin K.
AB  - There is consensus that late vitamin K deficiency bleeding (VKDB) should be
      prevented by vitamin K prophylaxis. One single dose of 1 mg vitamin K1 is
      effective if given i.m. or s.c., but not if given orally. Repeated oral doses
      might be as effective as the parenteral dose but the optimal dose regimen remains
      to be established. Different oral dose schedules are presently used in different
      countries. In Australia, Germany, The Netherlands and Switzerland active
      surveillance data on late VKDB were collected in a similar manner and failure
      rates compared. Identical case definitions were used. There were three basic
      strategies for oral and one for parenteral vitamin K prophylaxis for healthy
      newborns in the four countries: (1) daily supplementation of low dose vitamin K
      (25 micrograms) for breast-fed infants (The Netherlands); (2) 3 x 1 mg orally
      [Australia (January 1993-March 1994) and Germany (December 1992-December 1994)];
      (3) 1 mg vitamin K i.m. (Australia since March 1994); and (4) 2 x 2 mg vitamin K
      (new mixed micellar preparation) (Switzerland). The respective failure rates per
      100,000 live births (including cases given all recommended doses and those given
      incomplete prophylaxis) were for strategy: (1) 0.2 (0-1.3) in The Netherlands;
      (2) 2.3 (95% CI 1.6-3.4) in Germany and 2.5 (1.1-4.8) in Australia (oral
      prophylaxis); (3) Australia (i.m. prophylaxis) 0 (0-0.9); and (4) 3.6 (0.7-10.6)
      in Switzerland. The failure rates for complete prophylaxis only were: strategy
      (1) 0 (0-0.7) in The Netherlands; (2) 1.8 (1.1-2.8) in Germany and 1.5 (0.5-3.6)
      in Australia; (3) Australia (i.m.) 0 (0-0.9); and (4) 1.2 (0-6.5) in Switzerland.
      CONCLUSIONS: The Australian data confirm that three oral doses of 1 mg vitamin K
      are less effective than i.m. vitamin K prophylaxis. A daily low oral dose of 25
      micrograms vitamin K1 following an initial oral dose of 1 mg after birth for
      exclusively breast-fed infants may be as effective as parenteral vitamin K
      prophylaxis. The effectiveness of the "mixed-micellar" preparation of vitamin K1
      needs further study.

PMID- 9039518
TI  - Surfactant proteins and stable microbubbles in tracheal aspirates of infants with
      respiratory distress syndrome: relation to the degree of respiratory failure and
      response to exogenous surfactant.
AB  - Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM)
      count were measured in tracheal aspirates from infants with respiratory distress
      syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or
      no surfactant (control group, n = 12), and those without RDS (non-RDS group, n =
      8) to determine biochemical and biophysical status of surfactant in the course of
      RDS after surfactant replacement. Surfactant therapy resulted in immediate and
      sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory
      index to levels measured in the non-RDS group, whereas these indices improved
      slowly in the control group. The SP-A/ ALB was initially low in both RDS groups
      and increased to levels measured in the non-RDS group by age 48 h. Multiple
      regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A
      plus SP-BC, and surfactant therapy were independently associated with the
      severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of
      samples = 256). Infants with a relapse response to surfactant (n = 9) had levels
      of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n =
      23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24
      and 96 h of age. CONCLUSION: Surfactant therapy normalizes the surfactant and
      respiratory status of infants with RDS. Surfactant dysfunction rather than
      depletion may explain the relapse response seen in some surfactant recipients.

PMID- 9039520
TI  - Fatty acid composition of human milk during the 1st month after term and preterm
      delivery.
AB  - The fatty acid composition of human breast milk was determined longitudinally
      after term and preterm delivery by high resolution gas liquid chromatography.
      Milk samples were obtained at days 5, 10, 20 and 30 after term (n = 38) or
      preterm (n = 19) delivery. The saturated fatty acids C10:0 and C12:0 and the
      polyunsaturates linoleic acid (C18:2 omega-6) and alpha-linolenic acid (C18:3
      omega-3) increased significantly from day 5 to day 10, whereas arachidonic acid
      (C20:4 omega-6), total omega-6 long-chain polyunsaturates (LCP), docosahexaenoic
      acid (C22:6 omega 3) and total omega-3 LCP decreased significantly. Term and
      preterm milk did not differ in percentage content of linoleic acid, alpha
      linolenic acid and LCP at any time point. Preterm milk contained significantly
      more medium and intermediate chain fatty acids (C10:0, C12:0 and C14:0) than term
      milk on days 5 (12.28 vs 9.78%; P > 0.05), 10 (16.25 vs 12.62%; P > 0.05) and 20
      (17.29 vs 13.47%; P > 0.005). CONCLUSION: The milk of mothers of preterm infants
      is not better suited to meet the high LCP requirements of their infants during
      the first weeks after birth. The slightly higher proportion of medium and
      intermediate chain fatty acids in preterm milk during the 1st month after birth
      might be advantageous for the fat and calcium absorption of preterm infants.

PMID- 9039519
TI  - The effect of blood transfusion on oxygenation in premature ventilated neonates.
AB  - The effect of blood transfusion to maintain a preset packed cell volume (PCV)
      level in preterm ventilated infants has been investigated. Fifty infants, median
      gestational age 26 (range 23-33) weeks and postnatal age 4 (1-29) days,
      transfused a median of 15 ml/kg of blood in response to a PCV < or = 40% were
      retrospectively identified and their medical records reviewed to determine the
      change in PCV and haemoglobin resulting from the transfusions. In addition, their
      mean airway pressure (MAP) was noted and, as an index of oxygenation, their
      oxygenation index (OI), alveolar/arterial oxygen gradient (AaDO2) and
      arterial/alveolar (a/A) ratio calculated 12 h, 6 h and immediately prior to the
      transfusion and immediately post, 12, 18 and 24 h after the transfusion. The
      transfusion improved the PCV and haemoglobin (P < 0.0001). No significant changes
      in MAP or level of oxygenation were experienced in the 12 h prior to the
      transfusion. Post transfusion, despite no significant change in MAP, the AaDO2 OI
      and a/A ratios compared to immediately prior to the transfusion were
      significantly better at 12, 18 and 24 h. CONCLUSION: It is useful to transfuse
      ventilated preterm infants to maintain their PCV above a preset level.

PMID- 9039522
TI  - Case of the month: a 4-year-old girl with cardiac insufficiency and intermittent
      fever.

PMID- 9039521
TI  - Risk factors for hyperinflation in young schoolchildren born prematurely.
AB  - Lung function abnormalities, including hyperinflation, are common in young
      children born prematurely. The aim of this study was, in such patients, to
      determine factors associated with hyperinflation, that is an elevated lung
      volume. Lung volume was estimated by measuring functional residual capacity (FRC)
      before and after bronchodilator therapy in 41 5-year-old children who had been
      born prematurely at a median of 30 weeks gestational age. Hyperinflation was
      defined as an FRC greater than 120% of that predicted for height and a positive
      bronchodilator response as a greater than or equal to 10% change in FRC. Twelve
      (29%) of the children were symptomatic at 5 years, their median FRC (132%) was
      significantly higher than that of the asymptomatic children (109%), P < 0.01).
      Twelve (29%) children were hyperinflated; a greater proportion of the
      hyperinflated compared to the non-hyperinflated patients were symptomatic at 5
      years (7 or 58% versus 5 or 17%) (P < 0.05) and responded to bronchodilator
      therapy (9 or 75% versus 4 or 14%) (P < 0.01). Regression analysis demonstrated
      that hyperinflation related significantly only to current symptom status, but not
      perinatal variables. CONCLUSION: Hyperinflation in young children born
      prematurely reflects current symptom status and not adverse neonatal events.

PMID- 9039523
TI  - Recurrent bacterial meningitis.

PMID- 9039524
TI  - Conversion of selective IgA deficiency to common variable immunodeficiency in an
      adolescent female with 18q deletion syndrome.

PMID- 9039525
TI  - Reduction in birth weight in phenylketonuria.

PMID- 9039526
TI  - Alternating hemiplegia of childhood: treatment of attacks with chloral hydrate
      and niaprazine.

PMID- 9039527
TI  - Pyridoxine--responsive West syndrome and gamma-aminobutyric acid.

PMID- 9039528
TI  - Low prevalence of antibody to hepatitis C virus in children with chronic liver
      disease.

PMID- 9039529
TI  - Endotoxemia in febrile patients with hematological malignancies. Relationship of
      type of bacteremia, clinical findings and serum cytokine pattern.
AB  - The relation between gram-negative bacteremia, endotoxemia and cytokinemia in
      patients with hematological malignancies was studied. Serum endotoxin and
      cytokines (tumor necrosis factor-alpha, interleukin-1 receptor antagonist,
      interferon-gamma, interleukin-6 and interleukin-10) were determined in 24
      patients with hematological malignancies. Patients were included at start of
      fever (n = 18) or during a temperature peak during continuous fever (n = 6; time
      = 0). Blood was drawn for cultures at time of inclusion. Additional samples were
      obtained and grouped in two time intervals (1-5 h and 6-12 h after inclusion).
      Endotoxin was detected in eight patients. Endotoxemia was more common among
      patients with bacteremia than among non-bacteremic patients (7/12 versus 1/12; p
      < 0.05). All studied cytokines showed a tendency to higher mean values at time 0
      in patients with endotoxemia than in patients without endotoxemia. Significantly
      higher mean endotoxin values were seen at time 1-5 h in patients with gram
      negative bacteremia (n = 6) than in patients without gram-negative bacteremia,
      and at time 0 in patients with chills (n = 6) compared to those without chills.

PMID- 9039530
TI  - Candidemia in intensive care unit patients: risk factors for mortality.
AB  - Aim of this study was to evaluate whether risk factors which predict the
      development of candidemia may also predict death in ICU patients with candidemia.
      During an 8-year-period all ICU patients whose blood cultures yielded Candida
      species (n = 40) were retrospectively evaluated in a case-control fashion. The
      average incidence of Candida bloodstream infections was 5.5 per 10,000 patient
      days, ranging from 2.4 in 1990 to 7.4 in 1994. C. albicans was the most common
      pathogen in candidemic patients, but the proportion of non-C. albicans strains
      showed an increasing trend during 1989-1993, with a major shift towards non-C.
      albicans species in 1994. The overall mortality of patients with candidemia was
      58%. Mortality was highest in the group of patients with multi-organ dysfunction
      syndrome, especially among those in need of hemodialysis. Risk factors for the
      development of candidemia, such as age, malignancy, steroid use, i.v.
      catheterization, and the use of broad-spectrum antibiotics were not correlated
      with mortality in the ICU patients studied.

PMID- 9039531
TI  - Food-borne and air-borne streptococcal pharyngitis--a clinical comparison.
AB  - Different vehicles of transmission of the same pathogen may induce different
      clinical manifestations of the disease. The hypothesis was tested that the
      clinical manifestation of food-borne streptococcal pharyngitis is different from
      air-borne streptococcal pharyngitis. The symptoms and signs of 77 patients with
      endemic air-borne streptococcal pharyngitis compared to 103 patients with
      epidemic food-borne streptococcal pharyngitis (T type 8/25/imp19, M protein
      negative) and 11 patients with secondary air-borne epidemic streptococcal
      pharyngitis (T type 8/25/imp19, M protein negative) were prospectively evaluated.
      The patients with food-borne streptococcal pharyngitis had a significantly higher
      frequency of sore throat, fever, pharyngeal erythema, tonsillar enlargement and
      submandibular lymphadenopathy and a lower frequency of coryza and cough compared
      to the patients with endemic air-borne streptococcal pharyngitis. Although both
      food-borne and air-borne streptococcal infection caused upper respiratory tract
      infection, the clinical manifestation of food-borne streptococcal pharyngitis was
      more severe and more confined to the pharynx compared to the endemic air-borne
      disease. Involvement of the nasal mucosa and bronchial tree was more common in
      air-borne streptococcal pharyngitis than in the food-borne disease.

PMID- 9039532
TI  - A randomized comparison of two clarithromycin doses for treatment of
      Mycobacterium avium complex infections.
AB  - Two dosages of clarithromycin were compared for treatment of disseminated
      Mycobacterium avium disease of AIDS patients: high-dose (HD): 1,000 mg or 750 mg
      b.i.d. according to body weight, and low-dose (LD): 1,000 mg or 750 mg q.d.
      Patients with high probability of M. avium positive blood culture on day 0
      received a 42-day clarithromycin treatment with HD (n = 27) or LD (n = 28) at
      random after stratification according to body weight. Assessment procedures,
      including quantitative blood cultures, were performed at days 14, 28 and 42.
      Forty-five patients were eligible for clinical and 28 for bacteriological
      evaluation. Bacteriological success was observed in 12 HD and 11 LD patients,
      partial success in one HD and two LD and failure in none of the HD and two LD (p
      = 0.33). Between days 0 and 42, log decreases in CFU counts/ml were (mean +/- SD)
      3.13 +/- 0.82 (HD) and 2.67 +/- 1.8 (LD) (p = 0.38). Fever and night sweats
      significantly improved similarly in both groups; no change in spleen and liver
      size was observed on CT scans. Eight patients died during the study but no death
      was reported as drug related. Sixteen patients (HD = 6, LD = 10) discontinued the
      treatment because of side effects. A trend towards improved bacteriological
      effectiveness and reduced tolerance was observed in the HD group but the
      difference was not significant. With a power of 0.70, no dose effect was
      demonstrated between the two tested dosages. A daily dose of 1,000 mg
      clarithromycin was tested in drug combinations to treat disseminated M. avium
      infection in AIDS patients.

PMID- 9039533
TI  - Native and prosthetic valve endocarditis caused by Rothia dentocariosa:
      diagnostic and therapeutic considerations.
AB  - Three cases, one each of native valve, prosthetic valve and composite graft
      endocarditis caused by Rothia dentocariosa are described. The first patient
      presented with multiple brain abscesses and severe congestive heart failure due
      to destructive endocarditis with large vegetations on the mitral valve. He died
      shortly after emergency valve replacement. Gram-positive coccoid rods were
      identified in the vegetations of the excised mitral valve. The second patient had
      a R. dentocariosa endocarditis of a prosthetic aortic valve that was treated
      empirically with netilmicin and teicoplanin, due to an allergy to penicillin.
      Both antibiotics were replaced according to susceptibility testing in vitro with
      rifampin and ciprofloxacin, and the endocarditis was cured within 9 weeks. The
      third patient presented with a circular root abscess of an aortic composite graft
      that was successfully treated with rifampin and ceftriaxone without surgery. All
      patients had extensive periodontal disease which was thought to be responsible
      for hematogenic spread and seeding of the microorganism. The microbiological
      identification and antibiotic resistance pattern of the isolates, as well as
      therapeutic implications are discussed.

PMID- 9039534
TI  - In vivo and in vitro antifungal activity of the polyene derivative SPA-S-753
      against encapsulated form of Cryptococcus neoformans.
AB  - The in vitro and in vivo activity of SPA-S-753 (N-dimethylaminoacetyl-partricin A
      2-dimethylaminoethylamide diaspartate), a new water soluble polyene, was compared
      with amphotericin B against Cryptococcus neoformans in encapsulated (K) and
      nonencapsulated (N) morphological forms. In vitro tests against 17 isolates of C.
      neoformans (in K or N form) showed that SPA-S-753 activity is about ten times
      higher than that of amphotericin B. In direct contact tests the SPA-S-753
      cytocidal action was significantly higher than that of amphotericin B; the K
      cells are, however, less sensitive to the cytocidal action exerted by the two
      polyenes even when using concentrations 4-fold higher than those used against the
      N cells and they present a smaller potassium ion release. The cytocidal activity
      of the two polyenes is favoured by a low electrolyte concentration and an acid
      pH. SPA-S-753 microbicidal activity by contact in vivo, in mice infected with C.
      neoformans N cells by i.p. route, is more powerful than that of amphotericin B.
      In protection tests in mice infected with 10 LD50 of C. neoformans K cells, SPA-S
      753 action is again more powerful, but not to a significant degree, than that of
      amphotericin B. In conclusion, both substances showed a reduced in vitro and in
      vivo activity against C. neoformans in the K morphological form. Nevertheless our
      results demonstrate that SPA-S-753 exerts an antifungal overall activity that is
      more effective than that of amphotericin B under similar experimental conditions.

PMID- 9039535
TI  - Parvovirus B19 diagnosis in pregnant women--quantification of IgG antibody levels
      (IU/ml) with reference to the international parvovirus B19 standard serum.
AB  - On the basis of the results of a collaborative study the Expert Committee on
      Biological Standardisation of the World Health Organisation has issued an
      international standard (IS) serum for parvovirus B19 IgG antibody (NIBSC 93/724).
      In this study this IS was used to calibrate an in-house standard serum for
      reporting the results of parvovirus B19 IgG testing in IU/ml. The IgG titre
      distribution in 939 pregnant women was determined. These samples were sent to the
      laboratory for determining the immune status to parvovirus B19 following contact
      with parvovirus B19 infected individuals or for detecting acute infection in
      patients with symptoms suggestive of parvovirus B19 infection.

PMID- 9039536
TI  - Zidovudine and thymus humoral factor gamma-2 in the treatment of HIV infection:
      preliminary clinical experience.
AB  - A case-control, prospective, open-label, clinical trial to evaluate efficacy and
      safety of a combined zidovudine/Thymus Humoral Factor Gamma-2 (THF) therapy in
      HIV-infected subjects was conducted in 13 patients. Twenty-six patients were
      included as controls receiving only zidovudine. The two groups of patients were
      matched according to sex, age, CDC stage of HIV infection, number of CD4+ T cells
      and type of previous opportunistic infections (if any) and all patients and
      controls were naive for antiretroviral therapy at the moment they entered the
      trial. The observation period was protracted up to 47 months (mean 28 +/- 13
      months). No significant difference was observed between the two groups as far as
      surrogate markers of HIV disease progression are concerned. However, patients
      receiving zidovudine and THF showed a lower number of opportunistic
      complications. Only one patient in this group progressed to manifest AIDS while 9
      of 18 controls presented disease progression. Four patients died in the case
      group, all of them were CDC stage IV at admission, and 15 of 26 died in the
      control group (all CDC stage IV at admission, and four patients who presented
      disease progression during the study period). Survival time was increased in the
      case group. The exact immunological effect of thymus hormones in HIV infection
      has still to be elucidated, but a possible therapeutic role of these agents is
      foreseeable.

PMID- 9039537
TI  - Severe pancreatitis as first symptom of mumps complicated with pseudocyst and
      abscess of pancreas.
AB  - A 22-year-old man, a refugee from Bosnia, developed serious pancreatitis
      complicated with pseudocyst and pancreatic abscess. Staphylococcus aureus was
      isolated from pus and blood cultures. On day 12 of illness, parotitis and
      epididymitis appeared with elevated specific IgG antibody levels to the mumps
      virus. Surgical drainage and antibiotics were necessary for complete recovery.
      According to our observations, a significant number of hospitalized refugees
      during the war in Croatia had impaired host defences probably due to prolonged
      stress. A negative influence of these circumstances and/or the virulence of the
      agent should be considered in our patient as well.

PMID- 9039538
TI  - Tick-borne encephalitis: possibly a fatal disease in its acute stage. PCR
      amplification of TBE RNA from postmortem brain tissue.
AB  - Tick-borne encephalitis has occurred regularly in Europe since it was first
      diagnosed in 1931 by Schneider. The mortality rate of patients with this disease
      is 1-2%. Death usually occurs in the acute stage of illness. A case report of a
      28-year-old patient from Slovenia, who died shortly after the onset of tick-borne
      encephalitis, is described. The clinical course of disease, results of
      serological tests, neuropathological findings and polymerase chain reaction
      amplification of parts of viral genome from postmortem brain tissues are
      presented.

PMID- 9039539
TI  - Parenteral ganciclovir treatment of acute CMV infection in the immunocompetent
      host.
AB  - The treatment with ganciclovir of two non-compromised patients who required
      hospitalisation with acute cytomegalovirus (CMV) infection is described.
      Ganciclovir has rarely been used in such circumstances but, in four previously
      reported patients and in the patients described here, a rapid response to therapy
      was seen. In contrast to previous reports, relatively short courses of treatment
      (3-5 days) were given to our patients. The drug was well tolerated in each case
      and may have a role to play in the treatment of severe acute CMV infection in the
      normal host.

PMID- 9039540
TI  - Successful treatment of severe streptococcal toxic shock syndrome with a
      combination of intravenous immunoglobulin, dexamethasone and antibiotics.

PMID- 9039541
TI  - Prevalence of anti-HCV antibodies in chronic liver disease in the Czech Republic.

PMID- 9039542
TI  - Bacteremia due to teicoplanin-resistant and vancomycin-susceptible Staphylococcus
      haemolyticus in seven patients with acute leukemia and neutropenia receiving
      prophylaxis with ofloxacin.

PMID- 9039543
TI  - Increased frequency of sister chromatid exchange in Helicobacter pylori
      infection.

PMID- 9039544
TI  - Epidemiological and clinical aspects of mycobacterial infections.
AB  - The incidence of tuberculosis in the developed countries has recently started to
      rise again due to increased migration, a higher rate of direct transmission of
      Mycobacterium tuberculosis, and co-infection with HIV. The impact of the latter
      on the pathogenesis and presentation of tuberculosis is summarised. Important
      measures to prevent the further spread of tuberculosis include rapid diagnosis,
      prompt isolation of infectious patients, adequate control of treatment
      compliance, as well as surveillance of local resistance patterns. Disease due to
      the Mycobacterium avium complex is more frequent among HIV-infected patients in
      Central Europe than tuberculosis, and its development in the presence of immune
      deficiency seems to be mainly the result of a new infection with this ubiquitous
      microorganism rather than the reactivation of a previously acquired infection. It
      has a significant impact on mortality. The diagnosis of Mycobacterium avium
      complex infection requires a high degree of conjecture because most of the
      symptoms are non-specific, such as fever, night sweats, weight loss and anaemia.
      Promptly initiated treatment significantly prolongs the survival time of those
      affected by comparison with untreated patients.

PMID- 9039545
TI  - Diagnosis of tuberculosis and other diseases caused by mycobacteria.
AB  - The adequate diagnosis and treatment of tuberculosis depends on many events,
      including rapid pathogen detection, patient isolation, species identification,
      and drug susceptibility testing. Well trained staff, using state-of-the-art
      technology, are necessary in the mycobacteriology laboratory to produce timely
      results that are necessary for the patients' care and public health measures.
      Mycobacteriology laboratories still play a pivotal role in the control of
      tuberculosis, which is especially true in view of the spread of multidrug
      resistant tuberculosis. One way to optimize diagnostic efforts in spite of
      limited financial resources might be to sort and allocate specimens according to
      a system of priorities, e.g., diagnostic versus follow-up specimens. A "fast
      track" program for tuberculosis testing, which should be established as part of a
      dynamic diagnostic network, should focus on the highly infectious patient
      population. Collaboration between clinicians and mycobacteriologists remains the
      basis of dynamic diagnostic teamwork. Immediate screening of smears for acid-fast
      bacilli in patients suspected of tuberculosis, followed by immediate processing
      of smear-positive specimens using modern mycobacteriological technology, should
      be given high priority. Diagnosis of disease due to nontuberculous mycobacteria
      can be difficult. Nontuberculous mycobacteria are commonly found in nature, and
      assessment as to whether a nontuberculous mycobacterium isolate is clinically
      significant can be a difficult task.

PMID- 9039546
TI  - The use of rifabutin in Europe for the treatment of mycobacterial infection in
      AIDS patients.
AB  - The MICs of rifabutin on Mycobacterium avium are compatible with its efficacy in
      clinical infections. Two North American trials established the prophylactic
      effect of rifabutin in disseminated M. avium disease in AIDS patients. Several
      prospective non-randomized trials show the clinical and bacteriological efficacy
      of rifabutin. A large European study conducted from 1990 to 1993 randomized 382
      patients, selected on a clinical basis, to receive a combination of ethambutol +
      clofazimine + isoniazid + placebo or rifabutin for 12 weeks. Of these, 200 were
      eligible, i.e. had a positive blood culture at day 0. The percentage of patients
      with fever decreased from 78% to 23% in the rifabutin arm and from 76% to 11% in
      the placebo group (difference statistically not significant). The percentage of
      positive blood cultures decreased from 100% to 70% and 29% in the placebo group
      and from 100% to 45% and 18% in the rifabutin group at weeks 0, 6 and 12
      respectively. The rate of adverse events was 35% in the placebo and 30% in the
      rifabutin group (difference statistically not significant). Two other French
      randomized trials are being analysed: the first one compares a 14-day regimen of
      rifabutin to placebo. It shows a 70% success rate in the rifabutin arm and a 8%
      success rate in the control group. The second trial demonstrates that when given
      in addition to clarithromycin, unlike clofazimine a combination of rifabutin +
      ethambutol is effective in decreasing the relapse rate with acquired resistance
      to clarithromycin. After clarithromycin, rifabutin is the second drug which was
      proven to be active against disseminated M. avium disease in a controlled placebo
      trial.

PMID- 9039547
TI  - Prophylaxis against Mycobacterium avium-intracellulare complex infections in
      human immunodeficiency virus-infected patients.
AB  - Infection due to the Mycobacterium avium complex (MAC) accounts for the most
      frequent AIDS-related opportunistic infections, but MAC infection is usually not
      the first AIDS-defining event that a patient infected with HIV experiences. The
      incidence increases linearly over time, at a rate of 20 to 25% per year, after a
      patient's first AIDS-defining event, and the incidence increases exponentially as
      the CD4+ cell count approaches zero. There is evidence that MAC may eventually
      infect most if not all HIV-infected patients who do not die from another HIV
      related event. Since MAC infection contributes substantially to the morbidity and
      mortality of AIDS patients, prophylaxis appears to be mandatory. Rifabutin was
      the first drug which was shown to be effective in preventing MAC infection, and,
      recently, prophylaxis with clarithromycin was also found to prevent the disease.
      The optimal approach to prophylaxis still needs to be defined. Since a large
      majority of MAC infections occur in patients with CD4+ cell counts below
      50/microliter, recommendations regarding the prophylaxis of patients with a
      history of an AIDS-defining opportunistic event and a CD4+ cell count between 50
      and 200/microliter can be individualized, depending for example on how well the
      patient seems to be responding to antiretroviral treatment. Prophylaxis against
      MAC should be provided for any HIV-infected patient with a CD4+ cell count less
      than 50/microliter.

PMID- 9039558
TI  - Enterobacter sakazakii: a review.
AB  - Enterobacter sakazakii, previously referred to as a yellow-pigmented Enterobacter
      cloacae was designated as a unique species in 1980. This reclassification was
      based on differences from E. cloacae in DNA relatedness, pigment production and
      biochemical reactions. E. sakazakii has been implicated in a severe form of
      neonatal meningitis. Although studies have failed to identify an environmental
      source for the organism, dried-infant formula has been implicated in both
      outbreaks and sporadic cases of E. sakazakii meningitis. The high mortality rate
      (40-80%), the severity of the infection in infants, plus the scarcity of
      information on the ecology and pathogenicity of this organism warranted a review
      of the clinical and microbiological features of this putative foodborne pathogen.

PMID- 9039559
TI  - Identification of yeasts and coryneform bacteria from the surface microflora of
      brick cheeses.
AB  - Coryneform bacteria and yeasts of 21 brick cheeses from six German dairies,
      produced by using undefined ripening cultures, were identified. Arthrobacter
      nicotianae, Brevibacterium linens, Corynebacterium ammoniagenes, Corynebacterium
      variabilis and Rhodococcus fascians were found in significant numbers. Out of 148
      coryneform isolates 36 could not be identified at the species level. With the
      exception of a large rennet cheese, the coryneform microflora of rennet and acid
      cured cheeses were similar, but the cheeses had clearly different yeast
      populations. Debaryomyces hansenii and Galactomyces geotrichum prevailed in
      rennet cheeses while Kluyveromyces marxianus and Pichia membranaefaciens were the
      main species found in acid cured cheese. The dominance of Yarrowia lipolytica
      probably indicates an improper yeast population, resulting in poor cheese
      quality. Some of the species identified are potential candidates for designing a
      defined ripening culture for rennet red smear cheese.

PMID- 9039560
TI  - Anti-aflatoxigenic activity of Lactobacillus casei pseudoplantarum.
AB  - Lactobacillus casei pseudoplantarum 371 isolated from a silage inoculant was
      found to inhibit aflatoxins B1 and G1 biosynthesis by Aspergillus flavus subsp.
      parasiticus NRRI. 2999, in liquid medium. The inhibitory activity in the
      Lactobacillus cell-free supernatant was found to be sensitive to proteolytic
      enzymes such as trypsin and alpha-chymotrypsin, but resistant to pepsin. Lab
      Lemco tryptone broth (LTB), supplemented with 20% of dialyzed protein concentrate
      of the supernatant, totally inhibited the production of aflatoxins B1 and G1.
      When the protein concentrate was digested with trypsin, the production of
      aflatoxins B1 and G1 was restored. The inhibitory activity of the supernatant was
      inactivated within 10 min at 100 degrees C. A. flavus grown in the Lactobacillus
      cell-free supernatant did not produce a mutagenic response in the Salmonella
      mutagenicity test. However, Lactobacillus casei pseudo plantarum 371 did not have
      an effect on aflatoxin production and mold growth as measured by ergosterol and
      plate count, when the organisms were inoculated together on sterile steamed rice.

PMID- 9039561
TI  - Production, purification and characterization of reutericin 6, a bacteriocin with
      lytic activity produced by Lactobacillus reuteri LA6.
AB  - A bacteriocin (Reutericin 6) produced by Lactobacillus reuteri LA6, was purified
      by hydrophobic chromatography from the modified MRS broth (D'-MRS) with 6180-fold
      increase in specific activity with 14% recovery. The molecular weight of
      reutericin 6 was determined to be 2.7 kDa by SDS-PAGE and ESI-MS. By amino acid
      analysis, reutericin 6 comprised of 67% hydrophobic and polar neutral amino
      acids. Lanthionine was not detected. The lytic activity against Lactobacillus
      delbrueckii subsp. bulgaricus JCM 1002T and N1A1 B6 was detected by the decrease
      of both turbidity and the number of viable cells, and by leaking of beta
      galactosidase.

PMID- 9039562
TI  - Insufficient antilisterial capacity of low inoculum Lactobacillus cultures on
      long-term stored meats at 4 degrees C.
AB  - Two of the 210 lactobacilli strains isolated from chilled meats produced
      antilisterial bacteriocins: Lactobacillus sake 265 (Lb 265) and Lactobacillus
      casei 52 (Lb 52). Factors affecting antilisterial effectiveness of these and two
      other bacteriocin-producing (Bac+) strains (Lactobacillus sake 706, Lb 706; and
      Lactobacillus sake 148, Lb 148) at refrigeration temperature (4 degrees C) were
      studied in laboratory media and meat systems. At both 4 degrees C and 25 degrees
      C, these Bac+ strains grown in buffered MRS broths (pH 5.4 or 6.5) showed longer
      lag phases and shorter generation times than Listeria monocytogenes (mixture of
      strains NCTC 7973 and two food derived strains, L70 and L72) when grown in
      buffered BHI broths at the same pH values. These differences were more
      significant at 4 degrees C than at 25 degrees C. The highest concentrations of
      bacteriocin in MRS broth were produced at 25 degrees C and 4 degrees C by strain
      Lb 265 and Lb 706, respectively. Generally, production of bacteriocins was more
      efficient at lower pH (in buffered MRS broths of pH 5.4 and unbuffered MRS
      broths), than at higher pH (in buffered broths of pH 6.5). On vacuum packaged,
      raw beef (pH 5.3-5.4) initial numbers of L. monocytogenes (10(3)/g) did not
      change significantly during 23-days storage at 4 degrees C, when inoculated
      either alone or in the presence of Bac+ strains inoculated at initial levels of
      10(3)/g. On vacuum packaged emulsion-type of sausages (pH 6.4) inoculated with L.
      monocytogenes and stored at 4 degrees C for 23 days growth was not significantly
      affected by addition of Bac+ strains at initial levels of 10(3)/g. These results
      indicated that amounts of bacteriocins produced in situ by low initial numbers
      (10(3)/g) of the protective strains tested were not sufficient to inhibit and/or
      reduce L. monocytogenes on these chilled meats, where high initial numbers of
      lactic acid bacteria are not desirable for product quality resons. To achieve
      these effects, higher concentrations of active (free) bacteriocins in meats must
      be provided.

PMID- 9039563
TI  - Temperature distribution and prevalence of Listeria spp. in domestic, retail and
      industrial refrigerators in Greece.
AB  - The present paper examined the presence of Listeria spp. in the environment of
      domestic, retail and industrial refrigerators. From 136 household refrigerators,
      136 surface samples were taken from the walls or shelves, and 125 from cheese
      compartments. Only two refrigerators harboured L. monocytogenes. From 228 food
      store refrigerators, 335 samples were taken. Of these, 118 were in in contact
      with cheeses, 69 with sausages, 21 with cheese and sausages, 20 with
      miscellaneous products and 107 from refrigerator handles. Listeria spp. and L.
      monocytogenes were found in 3.1% and 1.7%, of the samples respectively. Listeria
      spp. was not detected in any of the nine dairy plant refrigerators examined.
      Listeria monocytogenes and L. innocua were found in 4.5 and 36.4%, respectively,
      of the 22 refrigerators inside meat processing plants, with only one of 22
      refrigerators handles being positive for L. monocytogenes. Temperature
      distribution in the refrigerators was also investigated. Fifty five per cent of
      the 136 domestic and 32% of the 228 retail store refrigerators had temperatures
      of greater than or equal to 9 degrees C. The range of refrigeration temperatures
      of the industrial refrigerators was 0-2 degrees C for meat plants and 2-7 degrees
      C for dairy plants. No correlation of any kind could be established between the
      prevalence of Listeria spp. and the temperature of the various refrigerators due
      to the low number of positive samples.

PMID- 9039564
TI  - The occurrence of Bacillus cereus in Danish pasteurized milk.
AB  - Four hundred and fifty eight samples of pasteurized full fat milk, pasteurized
      low fat milk (1.5% milk fat) and pasteurized double cream were collected from
      three Danish dairies (A, B and C) over a period of 1 year. The milk samples were
      stored at 7 +/- 0.5 degrees C for 8 days, and were then examined for the presence
      of Bacillus cereus and other aerobic mesophilic microorganisms. In addition, 115
      raw milk samples taken from weighing tanks at the three dairies were examined for
      psychrotrophic B. cereus. B. cereus was isolated from 257 (56%) of the 458
      pasteurized milk samples examined, and no differences between full fat milk, low
      fat milk and double cream were observed as regards the percentage of B. cereus
      positive samples. However, the mean count of B. cereus was significantly higher
      in double cream than in the other products. No significant differences was
      observed between the dairies. The prevalence of B. cereus in pasteurized milk
      products during summer and winter was 72 and 28%, respectively, and the mean
      counts of B. cereus was significantly higher during summer as well.
      Psychrotrophic B. cereus was detected in 29 of 115 samples of raw milk (25%). In
      120 of the 257 samples of pasteurized milk found to be positive, the viable count
      of B. cereus obtained was in the range between 10(3) and 3 x 10(5) cfu/ml.

PMID- 9039565
TI  - Lipolysis of pork fat by the meat starter culture Debaryomyces hansenii at
      various environmental conditions.
AB  - Lipolysis of pork fat by the meat starter culture Debaryomyces hansenii added at
      a level of 3.5 x 10(6) cells/ml was investigated at different temperatures (10-30
      degrees C), pH values (4.7-6.0). NaCl concentrations (2.5-7.5% w/v), and times of
      incubation (5-15 days). Pronounced growth was obtained amounting to 10(7)-10(9)
      cells/ml even at conditions combining the lowest temperature, the lowest pH and
      the highest NaCl concentration. Pork fat was hydrolysed to an extent depending on
      the environmental conditions. A quadratic polynomial model was developed
      describing the combined effects of environmental conditions on lipolysis.
      Regression analysis of data indicated that temperature, pH and time of incubation
      at conditions of meat fermentation were all significant factors in controlling
      lipolysis whereas NaCl concentration at the levels studied had no significant
      effect. Lipolysis increased when temperature increased. At 10 degrees C,
      lipolysis was very restricted even though growth was observed. An increase in pH
      resulted in higher lipolysis, the effect being most pronounced at high
      temperatures.

PMID- 9039566
TI  - Infection and removal of L-forms of Listeria monocytogenes with bred
      bacteriophage.
AB  - Phage breeding was employed to produce a bacteriophage (Listeria monocytogenes
      phage ATCC 23074-B1) which was specific for L-forms of L. monocytogenes. The bred
      phage was compared to its unbred parent for lytic activity and specificity. It
      was also tested for its ability to prevent L-form biofilm formation on stainless
      steel and compared with an organic acid (lactic) at L-form biofilm inactivation
      on stainless steel. The bred phage lysed only L-forms of L. monocytogenes in
      broth culture and only plaqued on L-form lawns. Likewise, the unbred phage
      performed similarly with classical cell-walled culture and lawns. The bred phage
      successfully inhibited L-form biofilm formation on stainless steel and was as
      successful as lactic acid (130 ppm) at inactivating pre-formed L-form biofilms.
      Both reduced viable cell numbers by 3-long cycles over a 6 h period. It appears
      that phage breeding technology may be an attractive alternative to chemical
      sanitizers which lack specificity and can be toxic.

PMID- 9039567
TI  - The combined effects of temperature, pH and NaCl on growth of Debaryomyces
      hansenii analyzed by flow cytometry and predictive microbiology.
AB  - Flow cytometry was applied to determine growth of Debaryomyces hansenii in a
      laboratory medium. Viable yeasts were enumerated after staining with the
      fluorogenic ester fluorescein diacetate (FDA). Initial studies showed that the
      flow cytometric determinations correlated well with viable yeast populations
      determined as colony forming units (CFU) whereas the relationship between CFU and
      optical density was only linear over a narrow range of cell concentrations,
      10(5.5)-10(7.5) cells/ml. The flow cytometric measurements could reliably detect
      D. hansenii at concentrations as low as 10(2) cells/ml whereas the lower
      detection limit using optical density measurements was 10(5)-10(6) cells/ml.
      Growth was determined by flow cytometry at different combinations of temperatures
      (10-30 degrees C), pH (4.7-6.0) and NaCl concentrations (1-12% w/v). Growth
      curves were generated by fitting a modified Gompertz equation to the growth data
      using non-linear regression analysis. Lag phase duration and maximum specific
      growth rates were derived and quadratic polynomial models were developed
      describing the effects of environmental conditions on the growth parameters.
      Model validation based upon repetition of experiments and use of another
      laboratory medium showed good agreement between observed and predicted maximum
      specific growth rates whereas predicted lag phases were shorter than the observed
      lag phases.

PMID- 9039568
TI  - Predictive modelling of growth of Listeria monocytogenes. The effects on growth
      of NaCl, pH, storage temperature and NaNO2.
AB  - The effect of NaCl concentration (5.0 115.0 g/l). pH value (4.0-7.2), temperature
      (1-35 degrees C) and NaNO2 concentration (0 200 mg/l) on the growth responses of
      Listeria monocytogenes, in laboratory medium was investigated. The growth curves
      generated within this matrix of conditions were fitted using the function of
      Baranyi and Roberts (1994) and the growth responses modelled using a quadratic
      polynomial to produce response surfaces. Growth curves could then be regenerated
      for any set of conditions within the experimental matrix and values predicted for
      the growth rate, doubling time, lag time and time to 1000-fold increase. The
      model was validated using data from published literature and was found to give
      realistic predictions for doubling times in foods, including meat and meat
      products, milk, dairy products and vegetables. Predictions from this model
      (Baranyi and Roberts. 1994) compared favourably with those from the models of
      Buchanan and Phillips (1990), Murphy et al. (1996) and the Food MicroModel.

PMID- 9039569
TI  - Growth and survival kinetics of Yersinia enterocolitica IP 383 0:9 as affected by
      equimolar concentrations of undissociated short-chain organic acids.
AB  - The influence of different organic acids (lactic, acetic, formic and propionic
      acids) at equimolar concentrations of undissociated acid with pH range of 3.9,
      5.8, on the aerobic and anaerobic growth and survival kinetics of the virulent
      strain of Y. enterocolitica IP 383 0:9, was determined in tryptone soy broth at 4
      degrees C. Growth and survival data were analyzed and fitted by a modification of
      the Whiting and Cygnarowicz-Provost model, using the Minpack software library.
      Initial generation times, initial specific growth rates, lag time and dead rate
      were subsequently calculated from the model parameters. The results demonstrate
      that the inhibitory effects of the acids were divided into two categories
      dependent upon pH. At high pH (5.8) the order of inhibition was formic acid >
      acetic acid > propionic acid > lactic acid, whereas at lower pH it became formic
      acid > lactic acid > acetic acid > propionic acid. The inhibitory effect of
      lactic acid is enhanced under anaerobic condition. Nevertheless, when the
      organism was cultured anaerobically, it was shown to be more tolerant to formic
      and acetic acids. Moreover, these variables (type of organic acid, pH and
      atmosphere) did not lead to the loss of the virulence plasmid in growing and
      surviving cells. The mechanism of inhibitory effect for each of the acids are
      also discussed.

PMID- 9039570
TI  - Munkoyo beverage, a traditional Zambian fermented maize gruel using Rhynchosia
      root as amylase source.
AB  - A typical munkoyo beverage was made by fermenting Rhynchosia heterophylla root
      extract-cooked maize meal mixture with Lactobacillus confusus LZI and
      Saccharomyces cerevisiae YZ20. The fermented munkoyo beverage had a pH of 3.3,
      lactic acid content of 60 mmol/l, ethanol 320-410 mmol/l and a characteristic
      'munkoyo' aroma. L. confusus, used alone, produced a beverage with a faint
      munkoyo flavour note whilst beverage produced with S. cerevisiae alone seemed not
      to have a typical munkoyo note. R. heterophylla root extract converted 75% of the
      starch in sterile cooked maize meat to maltose (80% of total sugars), maltotriose
      (17%) and glucose (3%) in I h at 45 degrees C. During fermentation by the mixed
      culture or the yeast alone most of the maltose was utilised but little or none of
      the maltotriose. The ratio of yeast to lactic acid bacteria in the starter
      culture affected the rate of production of ethanol but had no effect on the
      growth or acid production by the bacterium. To obtain a munkoyo beverage with the
      desired low alcohol concentration (< 100 mmol/l), the ratio of yeast
      concentration (cfu/ml) to Lactobacillus concentration in the starter culture
      should be 1:1000 or less and the beverage should be fermented for 24 h only.

PMID- 9039571
TI  - Characterisation of virulence factors of Serratia strains isolated from foods.
AB  - Out of 21 Serratia strains isolated from fresh juice and fish samples, five S.
      marcescens and two S. rubidaea caused lethality in mice on parenteral
      inoculation, but none through oral feeding. Three S. marcescens and one S.
      rubidaea produced heat-labile enterotoxin, detectible with the rabbit ligated
      ileal loop test, the mouse foot pad test and the vasopermeability factor test.
      Cell free culture filtrate (CFCF) of two enterotoxigenic S. mearcescens strains
      induced cytotoxic effect on a monolayer of Vero-cells, but CFCF of other
      enterotoxigenic strains could only induce cytotonic changes in Vero-cells. All
      strains possessed fimbriae type 3 while, only pathogenic strains had type 4
      fimbriae and a colonization factor. All pathogenic Serratia strains were
      agglutinated at comparatively lower salt concentrations than non pathogenic
      strains (< 1.3 M), and had multiple drug resistance. Their public health
      significance is also discussed.

PMID- 9039572
TI  - Effects of low temperatures (9-33 degrees C) and pH (3.3-5.7) in the loss of
      Saccharomyces cerevisiae viability by combining lethal concentrations of ethanol
      with octanoic and decanoic acids.
AB  - Octanoic and decanoic acids increase the rate of loss of Saccharomyces cerevisiae
      viability caused by lethal concentrations of ethanol, the specific death rate
      being an exponential function of the acid concentration. The highly liposoluble
      decanoic acid is the most effective. The fatty acids deleterious effect increases
      at pH below pKa (4.9) mainly due to the increase of the undissociated form
      concentration. The temperature effects (range 9 33 degrees C; at pH 3.9) on the
      kinetics of the toxin(s)-induced death suggest that the deleterious action of
      ethanol, octanoic acid and decanoic acid have the same biological target sites,
      probably related to transport processes across membranes, particularly the plasma
      membrane. In fact, the enthalpies of activation of octanoic acid- and decanoic
      acid-enhanced-ethanol-induced death were similar and close to the enthalpy of
      activation of ethanol-induced death. This average value (delta H++ = 11.4 +/- 2.7
      kcal/mol) is of the order of magnitude of that of solute transport across plasma
      membranes. Results clearly suggest the important contribution of octanoic and
      decanoic acids, combined with ethanol, in the loss of yeast viability at the last
      steps of industrial ethanolic fermentations, particularly those carried out at
      low or intermediate temperatures. They also support the combination of lipophilic
      acids with low pH in food preservation.

PMID- 9039573
TI  - The determination of efficacy of antimicrobial rinses on turkey carcasses using
      response surface designs.
AB  - Chlorine, lactic acid. TSP (trisodium phosphate) and a commercial phosphate blend
      (Avgard) were evaluated for their potential bactericidal effects on faecally
      contaminated turkey carcasses. Carcasses were sprayed for 10 s with each
      bactericide, at various concentrations and pressure combinations, derived from a
      response surface central composite design. For all the bactericides, variation in
      pressure had no significant (P > 0.05) effect in reducing either total or
      coliform counts. Lactic acid at various concentrations showed a significant
      effect (P < 0.20) in reducing total and coliform counts. The results indicate
      that lactic acid at 4.25% (w/w) has the potential for reducing the total
      microbial load and coliforms by more than 95%. Chlorine, TSP and Avgard
      concentration did not significantly (P > 0.20) affect the microbial load when
      compared with a water spray, i.e. no bactericide. Preliminary presumptive testing
      indicated that lactic acid and Avgard had some effect against Salmonella spp.
      Chlorine and TSP, irrespective of concentration and pressure, were not effective
      against Salmonella spp. Overall, these findings suggest that lactic acid was the
      most effective bactericide for reducing microbial contamination and improving the
      safety of poultry meat.

PMID- 9039574
TI  - The effect of ethylenediaminetetraacetic acid on heat resistance and recovery of
      Clostridium sporogenes PA 3679 spores treated in HTST conditions.
AB  - The effect of ethylenediaminetetraacetic acid (EDTA) on the heat resistance of
      Clostridium sporogenes PA 3679 spores was studied. EDTA was added to heating
      substrates and recovery media in order to establish which stage of the heat
      treatment registered the greatest EDTA activity. The heating substrates assayed
      were phosphate buffer (pH 7.0) and white asparagus puree, at natural pH (5.8) and
      acidified with citric acid and glucono-delta-lactone (GDL) to pH 5.5, 5.0 and
      4.5. Recovery of survivors was carried out in MPA3679A medium in various
      conditions of acidification with citric and GDL (250 and 500 ppm), at pH 7.5 6.5
      and 6.0. The results show greater activity of EDTA on spores when it was applied
      in recovery of heat injured spores, than during heating. The strongest influence
      of EDTA during heating was found in phosphate buffer (pH 7.0), with the effect
      being most evident at 121 and 126 degrees C, and in asparagus puree, at 121
      degrees C and pH 5.8 rather than acidified. In recovery, the inhibiting activity
      of EDTA was more evident in spores subjected to more severe heat treatment,
      either by increasing the exposure time or by raising the temperature to 130 or
      135 degrees C. The pH level of the recovery medium also affected the
      antimicrobial activity of EDTA, which had a greater inhibiting effect at pH 7.5
      than at lower pH levels (6.5, 6.0).

PMID- 9039575
TI  - Isolation and characterisation of Bacillus cereus from pasteurised milk in
      household refrigerators in The Netherlands.
AB  - The incidence and some characteristics (carbohydrate metabolism, growth profiles,
      haemolysin production and enterotoxin production) of Bacillus cereus, in
      pasteurised, low-fat (1.5%) milk, in household refrigerators in the Netherlands
      was investigated. In 247 (74%) of the 334 milk samples analyzed, the mesophilic
      aerobic counts were between 50 and 5000 per millilitre. B. cereus could be
      isolated from 133 (40%) of the samples. In general the B. cereus counts were low;
      numbers of less than five per millilitre were observed in 258 (77%) of the
      samples. As expected, both the mesophilic aerobic counts and levels of B. cereus
      increased with increasing storage temperatures in the refrigerator and prolonged
      storage times. In total, 143 presumptive B. cereus colonies were isolated.
      According to the ISO confirmation tests and the carbohydrate patterns (API 50
      CHB) 134 (94%) of these isolates were confirmed to be B. cereus. Of these 134
      isolates 20% fermented lactose and 53% of the 106 strains tested were able to
      grow at 7 degrees C. These percentages are much higher than expected for strains
      isolated from non-dairy products, suggesting that strains can adapt to
      environmental conditions in milk. All 106 strains tested, produced haemolysin,
      27% showed the discontinuous haemolytic pattern characteristic for haemolysin BL,
      possibly a virulence factor. Of the 37 B. cereus isolates tested for enterotoxin
      production 27 (73%), 28 (76%) and 26 (70%) were found to be enterotoxigenic (as
      determined by the Western immunoblot technique, polymerase chain reaction (PCR)
      and Vero cell assays, respectively). Isolates unable to ferment lactose, produced
      less enterotoxin in comparison with those able to utilize lactose. Although only
      a few outbreaks of food poisoning caused by B. cereus in milk (products) have
      been reported, most strains isolated from these products are able to produce
      enterotoxins and may represent a health hazard.

PMID- 9039576
TI  - Differences in pathogenicity for chick embryos and growth kinetics at 37 degrees
      C between clinical and meat isolates of Listeria monocytogenes previously stored
      at 4 degrees C.
AB  - Fifteen clinical strains of Listeria monocytogenes (eight strains of serogroup 4
      and seven strains of serogroup 1) and 15 meat isolates (all serogroup 1) were
      stored with no growth in phosphate-buffered saline (pH 7.0) at 4 degrees C for 4
      weeks. Pathogenicity for 14 day old chick embryos and growth kinetics in brain
      heart infusion (BHI) broth at 37 degrees C of the strains were determined before
      and after storage. Although no differences in pathogenicity between clinical and
      meat strains were found when tested as fresh cultures significant differences
      became apparent after cold storage. Firstly, the pathogenicity of clinical
      strains was not affected by storage, whereas the average mortality of embryos
      inoculated with meat strains decreased from 98.7 to 68.0%. Secondly, clinical
      strains subcultured at 37 degrees C had a significantly shorter average lag phase
      than meat strains after cold storage. The results of this study indicate that
      strains that caused human listeriosis have a higher resistance to the effects of
      unfavourable storage conditions than meat strains with respect to pathogenicity
      and lag phase duration at body temperature.

PMID- 9039577
TI  - Comparison of chemical treatments to kill Salmonella on alfalfa seeds destined
      for sprout production.
AB  - Outbreaks of salmonellosis in the US, Canada and Finland linked to alfalfa
      sprouts have been attributed to Salmonella stanley in 1995 and Salmonella newport
      in 1996. This study was undertaken to compare the efficacy of chemical treatments
      in killing a mixture of five Salmonella serovars inoculated onto alfalfa seeds.
      Solutions containing calcium hypochlorite or sodium hypochlorite at
      concentrations of 1800 and 2000 micrograms/ml active (available) chlorine
      respectively, as well as 6% hydrogen peroxide or 80% ethanol were effective in
      reducing Salmonella populations by more than 1000 fold. However, viable
      Salmonella cells were detected in seeds treated for 10 min in these solutions.
      The inaccessibility of Salmonella cells in crevices and between the cotyledon and
      testa of seeds to lethal concentrations of these chemicals are thought to be the
      reason for the lack of effectiveness.

PMID- 9039578
TI  - Analysis of metacarpophalangeal profiles by pattern recognition techniques.
AB  - RATIONALE AND OBJECTIVES: The author introduces a number of techniques well known
      in exploratory pattern recognition that can be used for the analysis of the shape
      of metacarpophalangeal profiles. It is shown that the classic Q-scores must be
      adapted for such techniques to be applicable. METHODS: A new set of scores (P
      scores) describing the shape of metacarpophalangeal profiles is derived. The
      application of various pattern-recognition techniques that use P-scores is
      described, using a collection of metacarpophalangeal length measurements in
      patients with various pathologic conditions. RESULTS: Different pattern
      recognition techniques highlight different aspects of the profiles, which, when
      interpreted together, yield a consistent understanding of the data set and
      insight in individual patients' peculiarities. CONCLUSIONS: The use of scale
      invariant scores is imperative when the shape of profiles is to be analyzed,
      especially in data sets with large variations in the scale factor. Methods of
      pattern recognition using such scores are of potential clinical interest.

PMID- 9039579
TI  - Distribution of trabecular and cortical bone related to geometry. A quantitative
      computed tomography study of the femoral neck.
AB  - METHODS: The relation between geometry and the distribution of trabecular and
      cortical bone mass and density in the human femoral neck was evaluated with
      quantitative computed tomography (QCT). Quantitative computed tomography data
      were obtained from 2-mm thick computed tomography slices of 20 human femur necks
      in vitro. A standardized scan position in each femur was used with the smallest
      cross-section as reference point. RESULTS: When trabecular bone mass (TrBM) and
      cortical bone mass were presented as percentage of total bone mass (ToBM), it was
      found that, starting at the cranial (head) side, ToBM consists of 78% TrBM. About
      21% of ToBM can be found as TrBM at the caudal (trochanter) side. At the smallest
      cross-sectional volume TrBM is 33% of ToBM. For every 2-mm slice, an average
      decrease of 5% TrBM can be seen. CONCLUSIONS: These data show that geometry and
      bone mass distribution are related. Whereas total bone mass remains relatively
      stable, the cortical and trabecular bone mass changes extensively. This implies
      that QCT measurements in the femoral neck depend highly on midneck positioning.

PMID- 9039580
TI  - Interventional atrioseptostomy by application of monopolar high-frequency
      alternating current. In vitro evaluation of a new device.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the use of a new device for
      interventional creation of atrial septal defects (ASD) working with high
      frequency alternating current in an in vitro study with porcine atria. METHODS:
      The device consists of a symmetrical cage of six superelastic monofile wires,
      including a microthermistor that is placed via a catheter into a punctured hole
      in the porcine foramen ovale. The device is used as a differential electrode for
      monopolar, temperature-controlled application of high-frequency alternating
      current for thermal modelling of ASD. RESULTS: Application of current for 60
      seconds caused temperature-dependent, sized ASDs. CONCLUSION: In vivo animal
      studies to evaluate possible side effects and long term patency of the ASDs are
      justified and warranted.

PMID- 9039581
TI  - Delineation of experimental liver tumors in rabbits by a new ultrasound contrast
      agent and stimulated acoustic emission.
AB  - RATIONALE AND OBJECTIVES: A new ultrasound contrast agent (SH U 563 A),
      consisting of hollow biodegradable polymeric microparticles, and a new imaging
      technique (stimulated acoustic emission) were used for delineation of
      experimental liver tumors. After intravenous injection, these microparticles are
      phagocytosed by cells of the reticuloendothelial system (RES) and create a color
      coded signal using color Doppler. Because of the different distribution of
      phagocytic cells in healthy liver tissue and tumors, the delineation of focal
      lesions was to be tested. METHODS: Sixteen rabbits with VX2 liver tumors received
      doses of 0.15-mL SH U 563 A per kilogram of body weight intravenously. Liver
      investigations (UM9, HD1, L10.5, ATL, Bothell, USA) were performed in vivo before
      and after SH U 563 A application in B and color Doppler modes. Additionally, the
      liver and spleen of these rabbits were examined ex vivo in color Doppler. The
      sonographic diagnosis was confirmed by pathology. RESULTS: After application of
      SH U 563 A, the healthy liver tissue of all rabbits was characterized by a
      typical mosaic color pattern in vivo and ex vivo, using color Doppler. Entire VX2
      liver tumors were detectable exclusively in color Doppler after SH U 563 A
      application. This was possible in 14 of 16 rabbits in vivo and in all 16 livers
      ex vivo. Furthermore, all ex vivo investigated spleens were color enhanced
      homogeneously. Sonographic diagnoses were in accordance with pathologic findings.
      CONCLUSIONS: SH U 563 A, combined with stimulated acoustic emission, provides
      potential for delineation of small isoechogenic liver lesions by sonography.

PMID- 9039582
TI  - The total entropy for evaluating 31P-magnetic resonance spectra of the liver in
      healthy volunteers and patients with metastases.
AB  - RATIONALE AND OBJECTIVES: The authors describe the clinical status of liver
      tissue with only a single numerical quantity (total entropy) derived from
      spectroscopic data of 31P-magnetic resonance (MR) spectra. METHODS: Twenty-four
      patients with liver metastases and 20 volunteers were investigated with image
      guided volume selective 31P-MR spectroscopy on a 1.5-T whole body scanner. From
      each in vivo 31P-MR spectrum, the ratios of phosphomonoester (PME)/beta-adenosine
      triphosphate (ATP), inorganic phosphate (Pi)/beta-ATP and phosphodiester (PDE)/
      beta-ATP and the total entropy (H*) were calculated. Mean values and standard
      deviations were determined and significance of the differences were tested with
      Student's t test. RESULTS: For patients, the H* = 4.7 +/- 4.3, PME/beta-ATP 0.72
      +/- 0.28, Pi/beta-ATP = 1.00 +/- 0.39, PDE/beta-ATP = 1.68 +/- 0.59. For the
      volunteers, H* = 7.6 +/- 2.5, PME/beta-ATP = 0.39 +/- 0.15, Pi/beta-ATP = 0.90 +/
      0.19, PDE/beta-ATP = 1.25 +/- 0.28. The total entropy of patients' spectra
      showed significantly lower values compared with those of volunteers. PME/beta-ATP
      and PDE/beta-ATP of the patients increased and differed significantly from
      volunteer data. CONCLUSIONS: It was demonstrated that the results of in vivo 31P
      MR spectroscopy may be described with a single criterion by means of the total
      entropy.

PMID- 9039583
TI  - Evaluation of the temporal evolution of acute spinal cord injury.
AB  - RATIONALE AND OBJECTIVES: After receiving a controlled injury to the thoracic
      cord, five rats were examined on a 1.5-T magnetic resonance (MR) imaging system
      at regular intervals over 1 month to assess evolution of the injury. METHODS:
      After the rats received pentobarbital anesthesia, a T10 laminectomy was performed
      on them, which exposed the dura over the dorsal surface of the spinal cord. With
      the animal placed in a New York University weight-drop device, a 10-g rod with a
      flat brass tip was dropped (free-fall) from a height of 50 mm to impact the cord.
      After injury, the incision was closed with suture material. Each animal was
      imaged on the day of injury, and at 7, 14, and 28 days after injury. Before
      contrast injection was administered, sagittal sections were obtained with T2 fast
      spin echo and T1-spin echo technique. Each rat then received 0.3-mmol/kg
      gadoteridol (Gd HP-DO3A or ProHance) intravenously, with the T1 scan repeated. At
      28 days, the animals were killed, and the cord was fixed and embedded in paraffin
      for histologic evaluation. RESULTS: The intensity of cord enhancement in the
      region of injury, after intravenous (i.v.) contrast injection, was at a maximum
      on the day of injury, and it decreased in a steady fashion thereafter. The
      intensity was 11.7 +/- 0.6 on the day of injury, 9.7 +/- 2.6 on day 7, 6.3 +/-
      5.3 on day 14, and 0.0 +/- 2.3 on day 28. The results on day 0 and 7 were
      statistically significant in terms of a difference from that on day 28, with a P
      value < 0.001. The length of cord injury, assessed postcontrast, also decreased
      in a steady fashion from the day of injury. The length of injury (in cm) was 1.1
      +/- 0.1 on the day of injury, 0.5 +/- 0.2 on day 7, 0.3 +/- 0.1 on day 14, and
      0.1 +/- 0.1 on day 28. The results on day 0 and 14 were statistically significant
      in terms of a difference from those at the next time point, with P values from <
      0.01 to < 0.001. Visually, on T2 images, substantial edema was noted on day 0,
      with progression to focal cord atrophy and gliosis by day 28. CONCLUSIONS: Acute
      spinal cord injury in a rat model is well visualized on pre- and postcontrast MR
      scans at 1.5 T. Observation of T2 changes and disruption of the blood-spinal cord
      barrier provide markers for temporal assessment of spinal cord injury in the rat
      model.

PMID- 9039584
TI  - Gadopentetate dimeglumine and iodinated contrast media. Hemodynamic side effects
      after bolus injections in pigs.
AB  - RATIONALE AND OBJECTIVES: The use of bolus injections of contrast media
      containing gadolinium for magnetic resonance imaging and their potential use as x
      ray absorbents require the evaluation of possible cardiovascular side effects.
      The hemodynamic reactions of high doses (0.6 mmol/ kg) of gadopentetate
      dimeglumine (gadolinium [Gd]-DTPA, Magnevist) were evaluated and compared with
      the side effects of ionic (diatrizoate: Urografin 76%) and nonionic (iopamidol,
      Solutrast 370) radiographic contrast media. METHODS: In 18 pigs, pressure and
      flow of the systemic and pulmonary circulation were monitored after intracardiac
      bolus injections (2-4 seconds) of dose volumes of 1.2 mL/kg of each contrast
      agent. RESULTS: All contrast media decreased the aortic pressure transiently (Gd
      DTPA and diatrizoate: -25%, iopamidol: -10%; P < 0.01). Pulmonary artery
      pressure, cardiac output, and stroke volume increased for several minutes. The
      vascular resistance declined. Diatrizoate induced stronger and longer-lasting
      side effects (P < 0.01) than Gd-DTPA and iopamidol. CONCLUSIONS: Despite of
      similar osmolality, Gd-DTPA induced weaker side effects than equivolumetric
      applications of diatrizoate. Other than osmolality, other factors such as
      viscosity and chemotoxicity influence the side effects of contrast media.

PMID- 9039586
TI  - Computation of the solvent-accessible surface area of monomer nonionic contrast
      media. Consequences for used probe radius in the study of hydrophilic
      characteristics.
AB  - RATIONALE AND OBJECTIVES: The solvent-accessible surface areas of different
      monomer nonionic contrast media were calculated for different probe radii. By
      correlating these areas with an experimental (octanol/water partition
      coefficient) and a calculated parameter (COMB-C), implications for the radius of
      the probe volume are pointed out. METHODS: The solvent-accessible surface areas
      of seven monomer nonionic iodinated contrast media were calculated with GEPOL (a
      program able to calculate various molecular surfaces and volumes) for a wide
      range of probe radii of the solvent. These areas were correlated with the
      octanol/ water partition coefficient and COMB-C, a parameter describing the
      spatial distribution of the hydrophilic elements of a molecule. RESULTS: The
      correlation coefficients of the solvent-accessible surface areas (determined with
      the different probe radii) with the octanol/water partition coefficient and of
      the solvent-accessible surface areas (determined with the same probe radii) with
      COMB-C were good. This correlation was better for probe raddi of 3 A or more.
      CONCLUSIONS: COMB-C, a parameter designed earlier, correlated well with the
      hydrophilia of a monomer nonionic contrast molecule. It was shown that a probe
      radius of at least 3 A should be used when correlations with hydrophilic
      characteristics are studied, rather than a probe radius of 1.5 A, which is
      generally used in assessment of solubilities of molecules in biologic
      environment. Implications are discussed.

PMID- 9039585
TI  - Gray-scale second harmonic imaging of the liver with galactose-based
      microbubbles.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the efficacy of SHU 508A, a
      galactose-based contrast agent used in gray-scale second harmonic imaging in
      vitro and in vivo experiments. METHODS: A Toshiba prototype harmonic imaging
      system (2.5/5.0 MHz) was used with SHU 508A in a phantom experiment and to image
      the liver in five healthy rabbits and one rabbit that had VX-2 tumors in the
      liver. RESULTS: In the second harmonic imaging, most of the fundamental
      components of the backscattered echo were eliminated, and good images with high
      contrast were obtained in the phantom experiment. Liver parenchyma was enhanced
      clearly in all rabbits at 0.3 mL/kg, an effect that lasted for 90 seconds. The
      tumor, which was mostly necrotic, was depicted clearly as a negative enhanced
      area surrounded by enhanced healthy liver. CONCLUSIONS: Gray-scale second
      harmonic imaging is a promising new method for visualization of perfusion of
      organs.

PMID- 9039587
TI  - MR imaging contrast agents--what's in a name?
AB  - The purpose of this brief review is to reduce the confusion surrounding the
      nomenclature of MRI contrast agents. There are several different categories of
      contrast agents for potential use in human diagnosis and several alternative
      names for each contrast agent, an array of choices that actually changes over
      time. This review describes the general process by which these various agents are
      named, presents one general categorization by which these agents can be
      considered, and provides a concise table to which readers can refer to identify
      the proper name to use for each of the agents that has thus far been administered
      to humans.

PMID- 9039588
TI  - Principles of contrast enhancement in the evaluation of brain diseases: an
      overview.
AB  - Intravenous contrast media are widely used in MR imaging of the brain. Clinical
      utility is high in both neoplastic and non-neoplastic disease. The agents
      approved to date are all gadolinium chelates, with extracellular distribution and
      renal excretion. The agents differ in regard to the maximum dose that can be
      administered and the theoretical safety margin. When administered at the same
      dose, the efficacy of the different available agents is comparable. Described in
      the following review article are the diagnostic use of contrast media and the
      patterns of enhancement encountered in neoplastic disease, infection, vascular
      disorders, and diseases of white matter. Only in congenital brain disease, when
      acute abnormalities are not suspected clinically and neoplastic disease is not a
      question, is contrast enhancement not indicated. The gadolinium chelates play a
      major role in the evaluation of patients by MR with known or suspected brain
      disease. These agents improve both the sensitivity and specificity of the
      examination. In many cases, lesions cannot be identified before contrast
      administration. Lesion delineation, assessment of lesion activity, and
      differential diagnosis are all improved, in general, with the addition of
      postcontrast scans. The scope of applications continues to expand as the modality
      and clinical experience matures.

PMID- 9039589
TI  - Effects of contrast dose, delayed imaging, and magnetization transfer saturation
      on gadolinium-enhanced MR imaging of brain lesions.
AB  - This paper discusses the types of paramagnetic agents available for clinical
      brain imaging and reviews investigations that have sought to optimize the use of
      these agents by varying the administered dose, delaying the imaging time after
      contrast administration, and altering image contrast by using magnetization
      transfer saturation pulses.

PMID- 9039591
TI  - Contrast-enhanced MR imaging in the evaluation of treatment response and
      prediction of outcome in multiple sclerosis.
AB  - MR imaging is becoming increasingly important in the evaluation of multiple
      sclerosis based on its sensitivity to acute, often subclinical events in the
      brain and because it provides a basis for measuring the accumulation of disease
      over time. Contrast-enhanced MR imaging in particular evaluates disease at the
      fundamental level of events affecting the blood-brain barrier. This review
      emphasizes (a) recent developments in the use of contrast-enhanced MR imaging as
      a measure of disease in patient groups and individuals and (b) its emerging role
      in evaluating new therapies.

PMID- 9039590
TI  - Application of contrast agents in the evaluation of stroke: conventional MR and
      echo-planar MR imaging.
AB  - The availability of new therapeutic interventions, including neuroprotective
      agents and endovascular thrombolysis, has given new hope to patients suffering an
      acute stroke. Early intervention remains a key factor in the effectiveness of
      these new and traditional treatments. More importantly, the capability to assess
      the viability and reversibility of the ischemic tissue became essential for
      better delineation and differentiation of infarcted versus ischemic tissue and
      patient management. Abnormal MR imaging (MRI) findings during acute stroke
      usually reflect the underlying pathophysiologic changes, which can be classified
      into three sequential stages: (a) hypoperfusion, (b) cellular dysfunction and (c)
      breakdown of the blood-brain barrier. The first stage is a kinetic phenomenon
      (not biologic) and, therefore, can be detected immediately. Contrast agents
      accentuate the abnormal flow kinetics and facilitate the early diagnosis of
      ischemia using either conventional MRI or newly developed echo-planar perfusion
      imaging (EPPI). The demonstration of abnormal arterial or parenchymal enhancement
      on conventional MRI during acute stroke provides the earliest sign of vascular
      occlusion/stenosis. EPPI, in contrast, provides information related to
      microcirculation (< 100 microns) and tissue reserve (cerebral blood volume) that
      cannot be obtained by conventional angiography and is directly related to the
      target end-organ. Further information obtained from both contrast MRI and EPPI
      may have a predictive value in the clinical outcome of acute stroke patients.

PMID- 9039592
TI  - Use of gadolinium chelates in MR imaging of the spine.
AB  - Spinal disease can be divided into intramedullary, extramedullary-intradural, and
      extradural compartments. In the cord (intramedullary compartment), gadolinium
      chelates are useful to diagnose primary and metastatic tumors, inflammation, and
      demyelination, and to evaluate syringomyelia when a Chiari I malformation is not
      present. In the extramedullary-intradural compartment, gadolinium chelates are
      useful for the diagnosis of drop metastases, meningiomas, and schwannomas. In the
      extradural compartment, gadolinium chelates are most useful to distinguish
      recurrent disc herniation from epidural fibrosis in the postoperative back and
      may be useful to diagnosis the soft tissue component of osseous metastases.

PMID- 9039593
TI  - Contrast agents in functional MR imaging.
AB  - Contrast agents have greatly expanded the role of MR imaging (MRI) to allow
      assessment of physiologic, or "functional," parameters. Although activation
      mapping generally does not require contrast agents, other forms of functional
      MRI, including mapping of cerebral hemodynamics (eg, perfusion imaging), are best
      done with the use of contrast agents. Serial echo planar images are obtained
      after bolus injection of lanthanide chelates. Application of susceptibility
      contrast physics and standard tracer kinetic principles permits generation of
      relative cerebral blood volume maps. Deconvolution of cerebral blood flow and
      mean transit time parameters is also possible within technical limitations. By
      using diffusion and perfusion pulse sequences, an imaging correlate to the
      ischemic penumbra can be identified. Functional MRI perfusion imaging of
      intraaxial tumors is analogous to positron emission tomography for delineation of
      metabolic activity, yet may be even more sensitive to neovascularity and
      possesses improved image quality. Clinical applications include biopsy site
      selection and postirradiation follow-up. Further improvements in data analysis
      and map generation techniques may improve diagnostic accuracy and utility.

PMID- 9039594
TI  - Contrast agents for MR imaging of the liver.
AB  - The evolution of contrast agents for MR imaging of the liver has proceeded along
      several different paths with the common goal of improving liver-lesion contrast.
      These contrast agents are used to accentuate the inherent differences in liver
      lesion signal intensity through differential enhancement of proton relaxation
      within adjacent tissues. Contrast agents used for hepatic MR imaging can be
      broadly categorized into those that target the extracellular space, the
      hepatobiliary system, and the reticuloendothelial system. Although only a small
      number of liver contrast agents are currently available, others are rapidly
      proceeding through clinical trials and may soon be added to our clinical
      armamentarium. This article will briefly review the current clinical experience
      with these agents, discussing their mechanism of contrast enhancement,
      pharmacokinetics, and efficacy in the evaluation of focal liver lesions.

PMID- 9039595
TI  - Assessing tumor angiogenesis using macromolecular MR imaging contrast media.
AB  - MRI enhanced with a macromolecular contrast medium (MMCM) has previously been
      shown to estimate tumor microvascular characteristics that correlate closely with
      histologic microvascular density, an established surrogate of tumor angiogenesis.
      A similar MMCM-enhanced MRI technique has now been used to investigate the acute
      tumor microvascular effects of antibody-mediated inhibition of vascular
      endothelial growth factor (VEGF), a well-studied and potent angiogenesis
      stimulator. Athymic rats xenografted with a human breast carcinoma (MDA-MB-435)
      were imaged after administration of albumin-gadolinium diethylenetriamine
      pentaacetic acid (Gd-DTPA30) using a heavily T1-weighted three dimensional
      spoiled gradient-refocused acquisition in a steady-state pulse sequence before
      and 24 hours after treatment with anti-VEGF antibody (single dose of 1 mg).
      Changes in longitudinal relaxivity (delta R1) were analyzed using a bidirectional
      two-compartment kinetic model to estimate tumor fractional blood volume (fBV) and
      permeability surface area product (PS). Data showed a significant decrease (P <
      0.05) of tumor PS with respect to macromolecular contrast medium at 24 hours
      after treatment with anti-VEGF antibody. No significant change was observed in
      fBV. Suppression of tumor microvascular permeability induced by anti-VEGF
      antibody can be detected and quantified by MMCM-enhanced MRI. MRI grading of
      tumor angiogenesis and monitoring of anti-angiogenesis interventions could find
      wide clinical application.

PMID- 9039596
TI  - Iron oxide-enhanced MR lymphography: the evaluation of cervical lymph node
      metastases in head and neck cancer.
AB  - Accurate diagnosis of cervical lymph node metastasis is challenging, even with
      the latest computed tomography or MR equipment and technique. The lack of
      definitive criteria for distinguishing metastatic from benign nodes is a serious
      shortcoming of current imaging options. Dextran-coated, ultrasmall
      superparamagnetic iron oxide is a new MR contrast agent, which accumulates in the
      reticuloendothelial system of lymph nodes. Small iron oxide particles are taken
      up by macrophages within normal functioning nodes, reducing their signal on
      postcontrast MR because of the magnetic susceptibility effects of iron oxide.
      Metastatic nodes, on the other hand, remain high in signal on postcontrast T2*
      weighted gradient echo images. Early clinical experience in cancer patients
      suggests that iron oxide-enhanced MR lymphography is a valuable imaging technique
      that may improve diagnostic accuracy for nodal metastases. This article reviews
      development of superparamagnetic iron oxide compounds, their imaging
      characteristics, and clinical experience for evaluating head and neck cancer
      metastases.

PMID- 9039597
TI  - Physiologic measurements by contrast-enhanced MR imaging: expectations and
      limitations.
AB  - Contrast-enhanced magnetic resonance imaging (MRI) offers the opportunity to
      quantitatively assess physiologic properties of tissue, such as perfusion, blood
      volume, and capillary permeability. Use of such quantitation potentially allows
      tissues to be characterized in terms of pathophysiology and to be monitored over
      time, during the course of therapeutic intervention. The degree to which such
      quantitation is applicable relies heavily on simplified model descriptions of the
      tissue space and assumptions relating the signal intensity observed to the
      contrast agent concentration. This article presents a perspective on the use of
      quantitative contrast-enhanced MRI, analysis of the accuracy of derived
      physiologic parameters, and recommendations for pulse sequence choice.

PMID- 9039598
TI  - Modeling tracer kinetics in dynamic Gd-DTPA MR imaging.
AB  - Three major models (from Tofts, Larsson, and Brix) for collecting and analyzing
      dynamic MRI gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) data are
      examined. All models use compartments representing the blood plasma and the
      abnormal extravascular extracellular space (EES), and they are intercompatible.
      All measure combinations of three parameters; (1) kPSp is the influx volume
      transfer constant (min-1), or permeability surface area product per unit volume
      of tissue, between plasma and EES; (2) ve is the volume of EES space per unit
      volume of tissue (0 < ve < 1); and (3) K(ep), the efflux rate constant (min-1),
      is the ratio of the first two parameters (k(ep) = kPSp/ve). The ratio K(ep) is
      the simplest to measure, requiring only signal linearity with Gd tracer
      concentration or, alternatively, a measurement of T1 before injection of Gd
      (T10). To measure the physiologic parameters kPSp and ve separately requires
      knowledge of T10 and of the tissue relaxivity R1 (approximately in vitro value).

PMID- 9039599
TI  - Water diffusion and exchange as they influence contrast enhancement.
AB  - The contrast-enhanced magnetic resonance imaging (MRI) signal is rarely a direct
      measure of contrast concentration; rather it depends on the effect that the
      contrast agent has on the tissue water magnetization. To correctly interpret such
      studies, an understanding of the effects of water movement on the magnetic
      resonance (MR) signal is critical. In this review, we discuss how water diffusion
      within biological compartments and water exchange between these compartments
      affect MR signal enhancement and therefore our ability to extract physiologic
      information. The two primary ways by which contrast agents affect water
      magnetization are discussed: (1) direct relaxivity and (2) indirect
      susceptibility effects. For relaxivity agents, for which T1 effects usually
      dominate, the theory of relaxation enhancement is presented, along with a review
      of the relevant physiologic time constants for water movement affecting this
      relaxation enhancement. Experimental issues that impact accurate measurement of
      the relaxation enhancement are discussed. Finally, the impact of these effects on
      extracting physiologic information is presented. Susceptibility effects depend on
      the size and shape of the contrast agent, the size and shape of the compartment
      in which it resides, as well as the characteristics of the water movement through
      the resulting magnetic field inhomogeneity. Therefore, modeling of this effect is
      complex and is the subject of active study. However, since susceptibility effects
      can be much stronger than relaxivity effects in certain situations, they may be
      useful even without full quantitation.

PMID- 9039600
TI  - Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging.
AB  - With the advances in MR techniques, information related to tumor microcirculation
      now can be obtained in the clinical setting. This information can be valuable in
      the assessment of tumor blood supply/oxygenation status and tumor response to
      therapy. In this article, we review the tracer-kinetic modeling for tumor
      microcirculatory parameters derived from dynamic contrast MR imaging and report
      several preliminary results from both an animal model and early experience with
      human tumors. Despite the application of different MR protocols and tracer
      kinetic models, the initial results of these pioneer studies consistently support
      the role of MR-derived microcirculatory tumor parameters, in providing prognostic
      information to assess and predict the response of cancers to cytotoxic therapy.

PMID- 9039601
TI  - Performance of Gd-EOB-DTPA and superparamagnetic iron oxide particles in the
      detection of primary liver cancer: a comparative study by alternative free
      response receiver operating characteristic analysis.
AB  - The performance of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd
      EOB-DTPA) and superparamagnetic iron oxide (SPIO) particles in detecting liver
      cancer was compared using alternative free-response receiver operating
      characteristic (AFROC) analysis, which allowed observers to indicate both the
      confidence level and the locations of all perceived abnormalities. Axial T1
      weighted MR images (1.5 T) pre/post Gd-EOB-DTPA (25 mumol/kg) injection were
      obtained for 12 rats with chemically induced liver tumors (64 tumors). T2
      weighted images (T2WI) were obtained pre/post SPIO (10 mumol/kg) injection for
      the same animal. Liver signal-to-noise ratio (SNR), tumor-liver contrast-to-noise
      ratio (CNR), and histopathologic sections corresponding to MR images were
      obtained. In AFROC, the location and the confidence level for each tumor were
      indicated independently on MR images by four radiologists. By plotting true
      positive fraction and probability of false-positive per image, the area under the
      AFROC curve (A1) was estimated and statistically analyzed between each sequence.
      Either drug significantly improved tumor-liver CNR (P < .001) and tumor detection
      (diameter < or = 6 mm; P < .05). Gd-EOB-DTPA significantly (P < .05) improved the
      A1 in T1WI. There was no A1 difference between T2WI + SPIO and T1WI + Gd-EOB
      DTPA. Gd-EOB-DTPA-enhanced T1WI showed the same performance as SPIO-enhanced T2WI
      in detecting liver tumors.

PMID- 9039602
TI  - Ferumoxides and Tc-99m sulfur colloid: comparison of the tumor-to-liver uptake in
      focal nodular hyperplasia.
AB  - The tumor-to-liver uptake of two reticuloendothelial agents, namely ferumoxides
      and technetium-99m (Tc-99m) sulfur colloid, was compared in focal nodular
      hyperplasia (FNH). Twelve patients with FNH who had undergone ferumoxides
      enhanced MR imaging and planar Tc-99m sulfur colloid scintigraphy within 1 year
      were included from the study. Fourteen patients with FNH with a diameter larger
      than 3 cm were selected for the comparison. The tumor-to-liver ferumoxides uptake
      was calculated and the Tc-99m sulfur colloid uptake was assessed visually.
      Fermuoxides uptake was observed in all but one patient with FNH (mean tumor-to
      liver ratio = .36). The six tumors showing normal (n = 5) or increased (n = 1)
      radiocolloid uptake when compared to the liver accumulated more ferumoxides than
      the eight tumors showing decreased radiocolloid uptake (P < .01). However, in
      some tumors, no direct relation was observed between ferumoxides and Tc-99m
      sulfur colloid uptake. Our observations suggest that ferumoxides uptake might not
      exactly mimic Tc-99m sulfur colloid uptake in FNH.

PMID- 9039603
TI  - Contrast-enhanced MR imaging of the liver: comparison between Gd-BOPTA and
      Mangafodipir.
AB  - The purpose of the study was to evaluate the MR contrast agents gadolinium
      benzyloxypropionictetro-acetate (Gd-BOPTA) and Mangafodipir for liver enhancement
      and the lesion-liver contrast on T1W spin-echo (SE) and gradient-recalled-echo
      (GRE) images. Fifty-one patients (three groups of 17 patients each) with known or
      suspected liver lesions were evaluated with T1W SE (300/12) and GRE (77-80/2.3
      2.5/80 degrees) images before and after intravenous (IV) Gd-BOPTA (0.1 or 0.05
      mmol/kg) or Mangafodipir (5 mumol/kg) in phase II to III clinical trials.
      Quantitative analysis by calculating liver signal-to-noise ratio (SNR), lesion
      liver contrast-to-noise ratio (CNR), and spleen-liver CNR was performed. Liver
      SNR and spleen-liver CNR were always significantly increased postcontrast. SNR
      was highest after application of 0.1 mmol/kg Gd-BOPTA (51.3 +/- 3.6, P < .05).
      CNR was highest after Mangafodipir (-22.6 +/- 2.7), but this was not
      significantly different from others (P = .07). Overall, GRE images were superior
      to SE images for SNR and CNR. Mangafodipir and Gd-BOPTA (0.1 mmol/kg) provide
      equal liver enhancement and lesion conspicuity postcontrast. By all criteria,
      contrast-enhanced T1-weighted GRE were comparable to SE images.

PMID- 9039604
TI  - MR signal intensity changes in hepatic parenchyma with ductal dilation caused by
      intrahepatic cholangiocarcinoma.
AB  - MR images of the liver in 13 patients with surgically proven intrahepatic
      cholangiocarcinoma were reviewed retrospectively and correlated to the histologic
      analysis of surgical specimens. We paid special attention to the peripheral liver
      tissue with ductal dilation but without tumorous involvement. High signal
      intensity was observed in the hepatic parenchyma with ductal dilation on T1
      weighted spin-echo images (8 of 12) and spoiled gradient-recalled echo images
      (seven of seven), as compared with the contralateral hepatic lobe without duct
      dilation. The high signal intensity was not suppressed with fat saturation and
      showed enhancement after administration of contrast (11 of 12). Concurrent portal
      venous obstruction did not have significant effect on these findings (P < .05).
      Correlation with pathologic specimens suggested that this enhancement was
      associated with periportal fibrosis. The etiology of the high signal intensity on
      unenhanced spin echo or gradient-recalled T1-weighted image remains unclear.
      Radiologists should recognize these findings and should distinguish these from
      tumor involvement or the arterial buffer response caused by portal venous
      obstruction.

PMID- 9039605
TI  - MR imaging of the liver: effect of portal hypertension on hepatic parenchymal
      enhancement using a gadolinium chelate.
AB  - The purpose of this study was to prospectively investigate the extent to which
      reduced portal blood flow in patients with hepatic cirrhosis and portal
      hypertension affects hepatic parenchymal enhancement during gadolinium-chelate
      enhanced dynamic MR imaging. Breath-hold three-dimensional (3D) spoiled gradient
      recalled echo (GRE) MR imaging technique obtained after intravenous
      administration of a gadolinium chelate was used to measure hepatic parenchymal
      enhancement and time to peak enhancement in 20 patients with hepatic cirrhosis
      and clinical evidence of portal hypertension (group 1) and in 20 control subjects
      without portal hypertension (group 2) who were matched for age, sex, and body
      weight. Mean peak hepatic enhancement values +/- SD and times to peak enhancement
      +/- SD were determined for both groups of patients. Mean peak enhancement value
      (+/-SD) was 78.7% +/- 36.2 in group 1 and 91.6% +/- 46.2 in group 2 (not
      significant). However, in the nine patients in group 1 with splenomegaly, mean
      peak enhancement value was 61.3% +/- 14.4, whereas it was 93.0% +/- 42.7 in the
      11 patients without splenomegaly (P < .05). Mean time to peak enhancement was 84
      seconds +/- 23 in group 1 and 54.0 sec +/- 25.0 in group 2 (P < .01). Our results
      show that mean peak enhancement value of hepatic parenchyma after intravenous
      administration of a gadolinium chelate is significantly altered for patients with
      portal hypertension and splenomegaly. In addition, the time to peak enhancement
      is delayed significantly when portal hypertension is present. Thus, it is
      possible that the optimal time for imaging the liver during the portal phase must
      be tailored to the status of the portal system of the patient.

PMID- 9039606
TI  - Evaluation of the hepatocyte-specific contrast agent gadobenate dimeglumine for
      MR imaging of acute hepatitis in a rat model.
AB  - This work was conducted to test the hypothesis that contrast-enhanced MRI with
      hepatocyte-specific contrast agents facilitates quantitation and mapping of
      diffuse liver diseases such as hepatitis and cirrhosis. Gadobenate dimeglumine
      (Gd-BOPTA/Dimeg, Bracco SpA, Millano, Italy) is a new paramagnetic hepatocyte
      specific contrast agent currently undergoing clinical trials. We have assessed
      the usefulness of gadobenate dimeglumine for the diagnosis of diffuse liver
      diseases in a rat model of chemically induced hepatitis. The study was based on
      the measurements of in vivo liver relaxation times as well as on the acquisition
      of standard SE images. Acute hepatitis considerably reduced the degree of T1
      shortening of liver parenchyma caused by intravenous injection of .25 mmol/kg of
      gadobenate dimeglumine. Analogously, the enhancement of the MRI signal intensity
      of the liver of rats with hepatitis observed in T1-weighted spin-echo (SE) images
      was inferior, in terms of both strength and duration, to that recorded in control
      rats at doses of .25 mmol/kg and .075 mmol/kg of gadobenate dimeglumine. Our
      results show that gadobenate dimeglumine-enhanced MR imaging has the potential
      for visualization of hepatitis and for assessment of liver function. Our
      conclusions differ from those previously published on this subject by other
      authors. The reasons that led to differing conclusions are discussed.

PMID- 9039607
TI  - Ampullary carcinoma: demonstration by current MR techniques.
AB  - The objective of this study was to demonstrate the appearance of ampullary
      carcinoma using current MR techniques, including fat suppression, gadolinium
      enhancement, and MR cholangiography. Nine patients with ampullary carcinoma were
      examined by MRI at 1.5 T. MR examinations included T1-weighted spoiled gradient
      echo, T1-weighted fat-suppressed, and immediate postgadolinium spoiled gradient
      echo images for all patients and MR cholangiography for three patients. The
      imaging features of ampullary carcinomas, including tumor size and morphology,
      signal intensity, and enhancement characteristics, were determined. Ampullary
      carcinomas shown on MR images ranged in size from 1.5 to 5.5 cm. Tumors were low
      in signal intensity on precontrast T1-weighted spoiled gradient echo and T1
      weighted fat-suppressed images relative to normal pancreatic tissue and enhanced
      less than normal pancreas on immediate postgadolinium spoiled gradient echo
      images. Tumor conspicuity was greatest on immediate postgadolinium spoiled
      gradient echo images. MR cholangiography demonstrated high grade obstruction of
      the common bile duct and mild dilatation of the pancreatic duct at the level of
      the ampulla with abrupt termination of the ducts in two untreated patients and
      moderate dilatation of the common bile duct in one patient who had a biliary
      stent. Ampullary carcinomas can be demonstrated on MR images as small masses
      arising at the ampulla. Tumors are well defined on immediate postgadolinium
      spoiled gradient echo images.

PMID- 9039608
TI  - Renal cell cancer: incidence of hemorrhage on MR images in patients with chronic
      renal insufficiency.
AB  - This study describes the occurrence of hemorrhage in renal cancer in patients
      with chronic renal insufficiency as shown on MR images. Thirteen consecutive
      patients with chronic renal insufficiency who had histologically proven renal
      cancer and underwent MRI at 1.5 T were entered in the study. MR examinations
      included spoiled gradient echo (SGE) and T1-weighted fat-suppressed imaging pre-
      and postgadolinium administration. All renal cancers were well shown on MR images
      and were most clearly depicted on postgadolinium T1-weighted fat-suppressed
      images. Tumors in 12 of 13 patients had regions of high signal intensity on
      precontrast T1-weighted images. Histology demonstrated intratumoral hemorrhage in
      all 12 of these patients. Four hemorrhagic tumors were largely cystic on imaging
      studies. One of these cancers altered in appearance from largely cystic with
      extensive hemorrhage to largely solid with substantial enhancement after a 2.5
      year interval. Renal cancers demonstrated minimal enhancement (11 patients) on
      early postgadolinium images and were minimally enhanced on delayed images in 10
      of 13 tumors. Two renal cancers demonstrated intense enhancement. Renal cancers
      are well shown on MR images in patients with chronic renal insufficiency. Because
      of the common occurrence of hemorrhage into renal cancers in patients with renal
      insufficiency, caution should be exercised when evaluating hemorrhagic cystic
      lesions in these patients.

PMID- 9039609
TI  - MR imaging of pelvic lymph nodes in primary pelvic carcinoma with ultrasmall
      superparamagnetic iron oxide (Combidex): preliminary observations.
AB  - The potential of ultrasmall superparamagnetic iron oxide (Combidex)-enhanced MRI
      of pelvic lymph nodes in patients with primary pelvic carcinoma is evaluated.
      Fifteen histologically classified lymph nodes in six patients with known primary
      pelvic cancer (four prostate; one rectum; one uterus) were evaluated with T2
      weighted fast spin-echo (FSE) and T2*-weighted gradient-echo (GRE) MRI at 1.5T 12
      to 48 hours after intravenous administration of Combidex at a dose of 1.7 mg
      Fe/kg. Quantitative image evaluation was performed by comparing signal intensity
      of individual nodes on pre- and postcontrast images. All patients proceeded to
      pelvic lymph-node biopsy or surgical dissection, where six were found to be
      benign and nine were malignant. Of the 15 lymph nodes, four nodes showed a
      decrease in signal intensity. Of these, three, in which signal loss was
      homogenous were benign, and one, in which the signal-intensity decrease was
      heterogeneous, was malignant (micrometastases). No signal change was noted in 11
      of 15 lymph nodes of which three were benign (inflammatory) and eight were
      malignant. Combidex is a promising MR contrast agent for evaluating pelvic lymph
      nodes. Our preliminary observations suggest that the agent is most useful for
      classifying normal lymph nodes.

PMID- 9039611
TI  - Gadolinium-enhanced MR angiography of visceral arteries in patients with
      suspected chronic mesenteric ischemia.
AB  - The purpose of this study was to evaluate accuracy of dynamic gadolinium-enhanced
      MR angiography (MRA) of the celiac, superior, and inferior mesenteric arteries in
      patients with suspected mesenteric ischemia compared with catheter angiography or
      surgery. Sixty-five patients with suspected mesenteric ischemia underwent three
      dimensional spoiled gradient-recalled acquisition in the steady state (GRASS)
      gadolinium-enhanced MRA. Correlative studies were performed on 14 patients,
      catheter angiography alone was performed on 12 patients, and surgery alone was
      performed on two patients. Six patients had mesenteric ischemia. In all patients,
      the celiac artery (CA) and superior mesenteric artery (SMA) were seen well enough
      to evaluate; however, the inferior mesenteric artery (IMA) could be evaluated in
      only 9 of the 14 patients. MRA showed severe stenosis (> 75%) or occlusion of the
      celiac axis in seven patients, of the SMA in six patients, and of the IMA in four
      patients. The overall sensitivity and specificity were 100% and 95%,
      respectively, compared with catheter angiography and surgery. The two errors were
      caused by overgrading the severity of IMA disease. Three-dimensional gadolinium
      enhanced MRA can accurately demonstrate the origins of the CA and SMA and is
      useful in evaluation of patients with suspected mesenteric ischemia.

PMID- 9039610
TI  - MR assessment of iodinated contrast-medium-induced nephropathy in rats using
      ultrasmall particles of iron oxide.
AB  - The purpose of this study was to determine the diagnostic value of ultrasmall
      particles of iron oxide (USPIO)-enhanced MR imaging at different concentrations
      to evaluate experimental nephropathy. This study was conducted in 23
      uninephrectomized rats using a model of iodinated contrast media-induced renal
      failure. Eleven rats received selective intra-arterial renal administration of
      diatrizoate (370 mg I/ml) and were compared to two control groups, including five
      animals injected with isotonic saline and seven noninjected animals. MR imaging
      was performed 28 hours after the procedure, including T1- and T2-weighted images
      before and after intravenous administration of successively 5 mumol Fe/kg and 60
      mumol/kg of USPIO. Results were interpreted qualitatively and quantitatively with
      respect to pathologic data, and differences were studied statistically. The
      maximal signal intensity decrease was noted in normal kidneys in cortex (-65 +/-
      4%) and medulla (-84 +/- 5%) on T2-weighted images after injection of 60 mumol/kg
      of USPIO. At this dose, diseased kidneys displayed less signal intensity decrease
      than normal kidneys on T2-weighted images (p = .05). Moreover, qualitative
      analysis showed that the highest sensitivity and specificity to diagnose kidney
      involvement were obtained with T2-weighted MR images (75% and 91%, respectively)
      when 60 mumol/kg of USPIO were used (p < .01). USPIO should be useful for in vivo
      evaluation of the severity of experimentally induced iodinated contrast media
      renal impairment in animals.

PMID- 9039612
TI  - Contrast-enhanced, ultrafast 3D pulmonary MR angiography in a single breath-hold:
      initial assessment of imaging performance.
AB  - An ultrafast three-dimensional (3D) sequence was developed, enabling the
      acquisition of 44 contiguous 2.0- to 2.2-mm thin sections, during intravenous
      application of paramagnetic contrast, in a single breath-hold. To estimate the
      potential clinical usefulness, images were assessed qualitatively and
      quantitatively with regard to visibility of main, lobar, segmental, and
      subsegmental pulmonary arteries. Five volunteers were examined using a 192 x 192
      matrix with an imaging time of 23 seconds and five other volunteers with a 160 x
      160 matrix (18 seconds). Each volunteer was imaged in apnea and during shallow
      respiration. The breath-held 23-second scans revealed excellent image quality and
      near complete visualization of central and segmental, as well as 81% of
      subsegmental, pulmonary arteries. Imaging time can be shortened to 18 seconds
      with only marginal loss in visualization performance (P < .05). Respiratory
      motion was found to cause significant worsening of image quality and vessel
      detectability. To maintain relevance in a clinical setting, imaging time can be
      minimized at the cost of a reduction in spatial resolution.

PMID- 9039613
TI  - Contrast-enhanced magnetic resonance angiography of carotid arterial wall in
      pigs.
AB  - This study was designed to investigate the effects of contrast agents on MR
      images of balloon-injured carotid arteries containing atherosclerotic-like
      lesions. We have evaluated an intravascular contrast agent, MS-325 (METASYN INC.,
      Cambridge, MA) and an extravascular contrast agent, Optimark, (Mallinckrodt
      Medical Inc., St. Louis, MO) on MR angiograms obtained 4 weeks after balloon
      hyperinflation-induced injury of the left common carotid artery in 12
      hypercholesterolemic minipigs. High in-plane resolution (.8 x .4 mm2), thin slice
      (1 mm) time-of-flight gradient echo sequences were used to acquire the MR
      angiographic images. Vascular lumen definition was compared before and after a
      single bolus intravenous injection of a contrast agent. Digital subtraction
      angiograms were obtained from all pigs after MR imaging. High grade stenosis
      developed in 1 of the 12 pigs and five pigs had complete occlusion of the injured
      vessel. The remaining pigs exhibited essentially no visible stenoses as assessed
      either by MR angiography or digital subtraction angiography. The vessel walls of
      the stenosed and occluded vessels were visible after the injection of either
      intravascular or extravascular contrast agent. Histologic analyses showed well
      developed neovascularization in the neointima or occlusive thrombosis. We
      conclude that the observed contrast-enhanced vessel wall is caused by an
      increased vascular supply associated with thrombosis and neointimal thickening
      that leads to an accumulation of contrast agent in the abnormal vessel walls
      after the injection of the T1-shortening paramagnetic contrast agent.

PMID- 9039614
TI  - Evaluation of portal MR angiography using superparamagnetic iron oxide.
AB  - The purpose of our research was to determine the effects of superparamagnetic
      iron oxide on MR imaging of the portal venous system. Eight piglets were examined
      in deep anaesthesia and respiratory arrest using a time-of-flight magnetic
      resonance fast low angle shot, two-dimensional angiography sequence at 1.5T, MR
      angiograms were acquired precontrast and after intravenous administration of a
      cumulative dose of 10, 20 and 40 mumol/kg SHU 555A, a superparamagnetic iron
      oxide contrast agent for MR imaging with a particle size of 60 nm. For each dose,
      two subsequent sets of scans were obtained and reconstructed by a maximum
      intensity-projection algorithm. Hepatic parenchymal and portal venous signal
      intensities were measured, and portal vein contrast calculated for each set of
      scans. All examinations were visually rated as to portal vein contrast and
      homogeneity by two blinded observers. Receiver operating characteristics of both
      observers were analyzed. The contrast agent reduced hepatic parenchymal signal in
      a dose-dependent way. After a cumulative dose of 10 mumol iron oxide, hepatic
      parenchymal signal intensity decreased to 63 +/- 6% (average of measurements at 4
      and 14 minutes, mean +/- standard error of the mean), after 20 mumol to 24 +/-
      3%, and after 40 mumol to 12 +/- 1% of control. Intravascular signal in the left
      main portal vein branch increased to 117 +/- 6%, 127 +/- 10%, and 133 +/- 9% of
      control, respectively. The contrast-to-noise ratio of the portal vein improved
      (521 +/- 90%, 891 +/- 178%, and 995 +/- 201% of control in the left portal vein
      main branch). Intravascular signal intensities increased slightly. The combined
      effect improved contrast of the portal vein stem and its branches. Receiver
      operating characteristics analysis documented dose-dependency of contrast medium
      effects on portal venous contrast and intravascular homogeneity. Visual rating
      also indicated a positive effect on portal venous contrast. The superparamagnetic
      iron oxide agent improved portal venous contrast with surrounding hepatic
      parenchyma in this normal animal model, and could potentially result in more
      accurate diagnosis of portal venous pathology.

PMID- 9039615
TI  - Evaluation of the iliac arteries: comparison of two-dimensional time of flight
      magnetic resonance angiography with cardiac compensated fast gradient recalled
      echo and contrast-enhanced three-dimensional time of flight magnetic resonance
      angiography.
AB  - We compared dynamic contrast-enhanced three-dimensional time of flight (3DTOF)
      magnetic resonance angiography (MRA) with two-dimensional time of flight (2DTOF)
      MRA with cardiac compensated fast gradient recalled echo (C-MON) and conventional
      angiography (CA) when it was available. C-MON re-orders the normal data
      acquisition to minimize ghosting artifacts generated by pulsatile flow. The
      initial phase of the study involved optimization of parameters and comparison C
      MON with no C = MON in eight patients and volunteers. The final phase of the
      study involved 53 patients who were imaged with contrast-enhanced 3DTOF MRA and
      2DTOF MRA with C-MON. Thirty of these patients also had CA. In the initial phase,
      2DTOF MRA with C-MON was found to be equal (n = 3) or superior (n = 5) to 2DTOF
      without C-MON. In the final phase, the agreement among all imaging modalities
      varied from substantial to almost perfect (Cohen's kappa = .6-.83). The lowest
      agreement was using 2DTOF to evaluate the external iliac segments. The among
      suggested treatments varied from substantial to almost perfect for all imaging
      modalities (Cohen's kappa = .73-93). The diagnostic efficacies of 2DTOF with C
      MON and contrast-enhanced 3DTOF were high overall, with the lowest value being a
      specificity of 63% for one reader in the evaluation of an external iliac segment
      using 2DTOF. In summary, 2DTOF with C-MON helped to eliminate artifacts due to
      pulsatility in the iliac arterial segments. In our experience, both dynamic
      contrast-enhanced 3DTOF MRA and 2DTOF MRA with C-MON performed well in the
      evaluation of the iliac arteries. Both studies have high interobeserver agreement
      and high diagnostic efficacy. Contrast-enhanced 3DTOF MRA should be reserved for
      situations in which the iliac vessels are extremely tortuous or occluded or the
      external iliac segments are poorly seen.

PMID- 9039616
TI  - Preliminary evaluation of a polyethyleneglycol-stabilized manganese-substituted
      hydroxylapatite as an intravascular contrast agent for MR angiography.
AB  - A blood-persistent particulate paramagnetic contrast agent has been formulated
      via size stabilization of manganese-substituted hydroxylapatite by a polyethylene
      glycol (PEG) bearing a terminal diphosphonate. At high PEG surface densities (35
      40 mol%), particles with mean diameter 8 +/- 2 nm were obtained. Relaxivities of
      autoclaved samples (at 20 MHz proton Lamor frequency) were R1 = 18.7 +/- .8 mM-1
      sec-1 and R2 = 22.3 +/- .7 mM-1 sec-1. The formulation persisted in rabbit blood
      with a biphasic clearance profile. Half-lives (with amplitudes in parenthesis)
      were 4 +/- 1 minutes (55%), and 49 +/- 3 minutes (45%), respectively, for the two
      phases. A dose of 40 mumol Mn/kg body weight enhanced the signal from rabbit
      vasculature for more than 45 minutes on MR angiograms. Thus, PEG-modified MnHA
      particles may find use as T1 agents for MR angiography.

PMID- 9039617
TI  - MR angiography with an ultrasmall superparamagnetic iron oxide blood pool agent.
AB  - The purpose of the study was to investigate the use of a dextran-coated
      ultrasmall superparamagnetic iron oxide (USPIO) as a blood pool contrast agent
      for thoracic and abdominal MR angiography. Abdominal and thoracic MR angiography
      was performed in six healthy volunteers using two-dimensional and three
      dimensional spoiled gradient echo (SPGR) sequences before and after intravenous
      administration of USPIO. Doses ranged from 1.1 to 2.6 mg Fe/kg. Flip angle was
      varied from 20 to 60 degrees. Subjective image quality, analysis of signal-to
      noise ratio (SNR), and blood T1 relaxation times were measured. USPIO
      significantly lowered the T1 of blood (from 1,210 ms precontrast to 159 ms
      postcontrast at a dose of 2.6 mg Fe/kg) (P < .01). Image quality on coronal fast
      three-dimensional breath-hold SPGR images of the abdomen increased with
      increasing dose and was maximum at the highest dose, producing an aortic SNR of
      9.6 compared to 1.8 precontrast. Axial two-dimensional time-of-flight (TOF)
      aortic SNR was reduced significantly from 13 on precontrast to 6 on the
      postcontrast images at the highest dose (P < .05) due to T2* shortening effects.
      There was little flip angle dependence on image quality. Due to the T1 shortening
      effect and long intravascular half-life, USPIO improved visualization of vascular
      anatomy using three-dimensional fast SPGR imaging. The echo time must be
      minimized to minimize signal loss from T2* shortening effects. The blood pool
      distribution of USPIO is useful for equilibrium-phase MR angiography.

PMID- 9039619
TI  - Effect of oxygen inhalation on relaxation times in various tissues.
AB  - The effect of the oxygen inhalation on relaxation times was evaluated in various
      tissues, including the myocardium, liver, spleen, skeletal muscle, subcutaneous
      fat, bone marrow, and arterial blood, with a [1H]MR system. Statistically
      significant decrease of T1 relaxation times was observed in the myocardium,
      spleen, and arterial blood after inhalation of 100% oxygen, whereas no
      significant change was observed in liver, skeletal muscle, subcutaneous fat, or
      bone marrow. The T2 relaxation time of these tissues did not differ significantly
      between before and after inhalation of the oxygen. These results indicate that
      [1H]MRI can be used to evaluate changes with oxygen inhalation and that the
      effect of the oxygen inhalation on T1 relaxation time is different among various
      tissues.

PMID- 9039618
TI  - Regional cerebral blood volume measured by dynamic susceptibility contrast MR
      imaging in Alzheimer's disease: a principal components analysis.
AB  - Dynamic susceptibility contrast (DSC) MRI is an alternative to positron emission
      tomography (PET) and single photon emission computed tomography (SPECT) for the
      evaluation of cerebral hemodynamics in patients with Alzheimer's disease. DSC MRI
      allows the construction of high resolution images of cerebral blood volume (CBV)
      without the use of radionuclides or ionizing radiation. In this study, DSC MRI
      data were collected from 16 patients with probable Alzheimer's disease and 16 age
      matched control subjects. Characteristic patterns of regional CBV variation were
      found using principal component analysis. Three such patterns were identified: a
      global variation pattern, an anterior-to-posterior CBV gradient, and a
      temporoparietal pattern. Group differences in the principal component scores
      associated with the global and temporoparietal patterns (P = .08 and P = .007,
      respectively) suggest that these deficits reflect characteristic CBV
      abnormalities in Alzheimer's disease. Using only these two scores, the
      Alzheimer's disease group was classified with a sensitivity of 81% and a
      specificity of 88%. Additionally, disease severity, as measured by the Mini
      Mental State Examination (MMSE), was correlated significantly with the third
      principal component score (Pearson's r = .50, P = .05).

PMID- 9039620
TI  - Preliminary experience with the application of gadolinium-DTPA before MR imaging
      guided laser-induced interstitial thermotherapy of brain tumors.
AB  - The purpose of this study was to investigate the potential value of i.v.
      gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) applied before MRI
      guided laser-induced interstitial thermotherapy (LITT) of brain tumors without
      original enhancement, especially in defining total lesion size during therapy.
      MRI-guided LITT was performed on two patients with astrocytoma WHO II. For both
      patients, Gd-DTPA was administered intravenously after a first irradiation period
      and LITT was continued after pulling back the light guide to coagulate the upper
      parts of the tumor. In both patients, the whole irreversible damaged zone of the
      second irradiation period after Gd-DTPA showed an intense increase of signal
      intensity. The spatial expansion correlated with the diameter of an enhancing rim
      after Gd-DTPA on follow-up studies. Our preliminary results indicate that the
      application of Gd-DTPA before MRI-guided LITT may be of value in defining exactly
      the size of the irreversible damaged zone during therapy in nonenhancing brain
      tumors.

PMID- 9039621
TI  - Dual dynamic contrast-enhanced MR imaging.
AB  - A method was devised for obtaining dynamic contrast-enhanced T1-weighted and
      relaxation rate (delta R2*) images simultaneously to evaluate regional
      hemodynamics of the brain tumors. On a 1.5-T MR system, dual dynamic contrast
      enhanced images were obtained using a gradient echo (dual echo fast field echo)
      pulse sequence with the keyhole technique to improve temporal and spatial
      resolution during a rapid bolus injection of gadopentetate dimeglumine. The
      dynamic T1 contrast images were obtained from the first echo: moreover. integral
      delta R2*dt values were calculated from the first and the second echo images. The
      dynamic T1 contrast images provided information about characteristic enhancement
      pattern (vascularization and disruption of blood-brain barrier), and the integral
      delta R2*dt values provided a map of regional blood pool in tumor site,
      peritumoral edema, and other surrounding regions of the brain. The ability to
      obtain dynamic contrast-enhanced T1 contrast and delta R2* imaging at the same
      time allows optimization of the advantages of each and thereby more information
      about the microvascular circulation of the brain lesions.

PMID- 9039622
TI  - Dynamic 3D-MR mammography: is there a benefit of sophisticated evaluation of
      enhancement curves for clinical routine?
AB  - The purpose of the study was to compare standard analysis with pharmacokinetic
      analysis of time-intensity curves in dynamic three-dimensional (3D) MR
      mammography (MRM) for their capability of differentiating benign from malignant
      disease. Dynamic MRM of the whole breast was performed at 1.0 T using an axial
      fast low-angle shot (FLASH) 3D sequence. For the standard evaluation, the
      enhancement of the first minute (E1) and the slope of enhancement from minute 2
      to 10 (SE2-10) were calculated. For pharmacokinetic analysis, the amplitude of
      enhancement (A), distribution time (t21), and elimination time (tel) were
      computed. Sixty-two histologically verified lesions were evaluated. The standard
      evaluation methods yielded a highly significant difference between benign and
      malignant disease for E1 (P = .0008) and SE2-10 (P = .0001). The pharmacokinetic
      parameters gained similarly significant P values (A, P = .0014; t21, P = .0024;
      tel, P = .0001). Both standard and pharmacokinetic analysis concordantly
      discriminated between benign and malignant lesions in discriminant analysis.
      Compared with standard analysis, a pharmacokinetic analysis of time-intensity
      curves is not beneficial for routine clinical diagnosis.

PMID- 9039623
TI  - Initial experience with dynamic MR imaging in evaluation of normal bone marrow
      versus malignant bone marrow infiltrations in humans.
AB  - The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR
      imaging of normal bone marrow versus malignant bone marrow infiltrations in
      patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b)
      correlation with the clinical stage according to Binet (stages A, B, C) and
      response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and
      proximal femurs was performed at 1.5 T in 45 patients without known malignancy
      and in 30 patients with B-CLL. The differences between opposed-phase and in-phase
      dynamic gradient-echo sequences before and up to 10 minutes after intravenous
      application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta
      acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast
      enhancement patterns of normal and malignant bone marrow were compared using the
      opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone
      marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up
      during therapy. Opposed-phase gradient echo sequences demonstrated a signal
      decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated
      a signal increase of normal bone marrow after administration of Gd-DTPA. The
      dynamic signal intensity time courses differed significantly (P < .05) between
      Binet stages B and C and controls as well as among the three Binet stages of B
      CLL. In the 10 patients followed during therapy, MR imaging sensitively
      demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial
      response (n = 2). In out-of-phase imaging, both normal bone marrow and initial
      bone marrow infiltration in CLL stage Binet A show signal decrease after
      administration of contrast agent, whereas there is increase in signal intensity
      in higher-grade bone marrow infiltration in Binet stage B or C disease. The
      signal loss of normal bone marrow in out-of-phase imaging is a phase effect
      rather than a T2* effect. The differentiation of initial from higher-grade bone
      marrow infiltration on out-of-phase images relies solely on a shift in the
      fat/water ratio.

PMID- 9039624
TI  - Low molecular weight lanthanide contrast agents: in vitro studies of mechanisms
      of action.
AB  - The MR contrast properties of a series of structurally dissimilar low molecular
      weight (LMW) gadolinium (Gd) and dysprosium (Dy) chelates have been investigated
      under controlled experimental conditions in various in vitro test systems.
      Relaxation analysis (water, pH = 5.8, 37 degrees C, .47 T) demonstrated the high
      dipolar relaxation efficacy of the tested Gd chelates. The T1 and T2 relaxivities
      of both metal chelate series decreased with decreasing hydration number,
      confirming the strong correlation between metal chelate structure and dipolar
      relaxivity. Susceptibility-induced T2 relaxation, commonly known as the
      susceptibility effect, is modulated primarily by the magnetic susceptibility and
      compartmentalization of the contrast agent. The influence of these parameters on
      the susceptibility effect of Dy diethylenetriamine penta-acetic acid bis
      methylamide (DTPA-BMA) and GdDTPA-BMA was investigated in two-compartment in
      vitro models. In red blood cell suspensions (45% hematocrit, 37 degrees C, .47 T,
      2 and 3 mM metal ion concentration), the T2 relaxation efficacy of DyDTPA-BMA was
      markedly improved due to susceptibility effects that were shown to depend on
      compartmentalization. As the relaxation ability of GdDTPA-BMA was modulated by
      the dipolar interactions, compartmentalization was not a prerequisite for its T2
      relaxation efficacy. In a coaxial glass system with no intercompartmental water
      exchange, which eliminated the dipolar relaxation mechanism, DyDTPA-BMA was shown
      to be the most efficient susceptibility agent because of its higher magnetic
      susceptibility. The reported one- and two-compartment model studies have
      demonstrated the different mechanism of action of LMW Gd- and Dy-based contrast
      agents. Gd chelates are predominantly dipolar relaxation enhancers, whereas Dy
      chelates are efficient susceptibility agents only in compartmentalized systems.

PMID- 9039625
TI  - Magnetically labeled cells can be detected by MR imaging.
AB  - To determine the feasibility of MR imaging of magnetically labeled cells,
      different cell lines were labeled with monocrystalline iron oxide (MION)
      particles. Phantoms containing MION labeled cells were then assembled and imaged
      by MR at 1.5 T using T1-weighted and T2-weighted pulse sequences. MION uptake
      ranged from 8.5 x 10(4) to 2.9 x 10(5) particles/cell for tumor cells (9L and
      LX1, respectively) to 1.5 x 10(6) to 4.8 x 10(8) particles/cell for "professional
      phagocytes" (J774 and peritoneal macrophages, respectively). On the T1-weighted
      images, cell-internalized MION appeared hyperintense relative to agar and similar
      to MION in aqueous solution. On T2-weighted images, signal intensity varied
      according to concentration of MION within cells. Cell-internalized MION caused
      similar MR signal changes of cells as did free MION; however, at a dose that was
      an order of magnitude lower, depending on the pulse sequence used. The
      detectability of MION within cells was approximately 2 ng Fe, which corresponded
      to 10(5) tumor cells/well or 5 x 10(3) macrophages/well. We conclude that a
      variety of cells can be efficiently labeled with MION by simple incubation.
      Intracellular labeling may be used for MR imaging of in vivo cell tracking.

PMID- 9039645
TI  - Protein kinase C involvement in the resting and interferon-gamma-induced K+
      channel profile of microglial cells.
AB  - The whole-cell configuration of the patch-clamp technique was used to study the
      involvement of protein kinase C (PKC) in the modulation of K+ channels in
      cultured microglia from newborn rats. We previously showed that 24-hr treatments
      with interferon-gamma (IFN-gamma) induce an increase of inward-rectifying (IR)
      and outward-rectifying (OR) current density and that the effect on OR was shared
      by bacterial lipopolysaccharide (LPS) (Visentin et al.: J Neurosci Res 42:439
      451, 1995). In the present study, IFN-gamma (1-500 U/ml, 24 hr) enhanced IR
      current density up to threefold. The IFN-gamma effect was not detectable after
      shorter treatments (1-5 hr) and was abrogated by a protein synthesis inhibitor.
      The PKC activator phorbol myristate acetate (PMA) also increased IR current
      density, whereas the inactive alpha-4 isoform was ineffective. When IFN-gamma and
      PMA were co-applied, the effect was more than additive. Among the PKC inhibitors
      tested, staurosporine (STA)-but not calphostin C (CALP)-abolished the effect of
      IFN-gamma and of PMA and antagonized only partially that of co-applied IFN-gamma
      and PMA. OR currents were affected by treatment (24 hr) with PKC modulating
      agents in an opposite fashion. PMA depressed OR currents in control and in IFN
      gamma (or LPS) treated cultures, even when added after pretreatment (with LPS)
      that was long enough to enhance OR channel expression. Both STA and CALP enhanced
      OR density in resting and IFN-gamma-stimulated cells but did not counteract the
      depressing effect of PMA. In conclusion, our data on IR suggest a relationship
      between the IFN-gamma effect on current density and PKC activation. However, we
      cannot conclude with certainty that IFN-gamma acts through PKC activation. Our
      data on OR support an inverse relationship between PKC activation and OR current
      density. Nevertheless, the lack of effect of PKC inhibitors on PMA-induced OR
      depression suggests that PMA may, in this case, act on a target different from
      PKC.

PMID- 9039646
TI  - Transcriptional regulation of neurofilament expression by protein kinase A.
AB  - RN46A cells, a conditionally immortalized neuronal cell line derived from E12 rat
      medullary raphe nucleus, upregulate low M(r) (68 kDa, neurofilament [NF]-L) and
      medium M(r) (160 kDa, NF-M) neurofilament protein expression upon activation of
      protein kinase A (PKA). To examine possible transcriptional regulation of
      neurofilament protein expression by PKA, two cell lines were used; RN46A cells
      and C alpha EV6 cells, a cell line derived from RN46A cells that stably expresses
      the catalytic subunit of PKA under the control of the metallothionein promoter.
      Treatment of RN46A cells with dbcAMP resulted in an increase in the steady-state
      levels of both NF-L and NF-M, but not high M(r) (200 kDa, NF-H) neurofilament
      mRNA. These increases were both time and dose dependent and were sensitive to
      treatment with the protein synthesis inhibitor cycloheximide. In C alpha EV6
      cells, activation of PKA by 80 microM ZnSO4 upregulated the expression of C alpha
      mRNA with maximal levels reached 8 hr post-treatment and maintained at 24 hr.
      Reporter gene assays in C alpha EV6 cells following transfection with increasing
      lengths of the NF-L promoter demonstrated that both a putative Sp1-like and a
      cAMP response (CRE), but not a NGFI-A, element were likely involved in PKA
      dependent activation of the NF-L promoter. Electrophoretic mobility shift assays
      confirmed these results but showed that the nuclear proteins induced by PKA which
      bound to the NF-L promoter Sp1-like sequence were not Sp1. Collectively, these
      data suggest that constitutively expressed Sp1 may be involved in basal NF-L
      promoter activity, and newly synthesized, PKA-dependent nuclear proteins may
      synergistically activate the rat NF-L promoter.

PMID- 9039647
TI  - Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells.
AB  - The cause of neuronal loss in Alzheimer disease is unknown. We investigated the
      effects on survival of PC12 cells expressing A692G, E693Q, and V717F mutant
      amyloid precursor proteins (APP). Differentiated cells expressing mutant APPs
      exhibited somal shrinkage, followed by cell detachment from the plates. Increased
      levels of oligonucleosome-sized DNA ladders and TUNEL-positive nuclei were
      observed, and electron microscopy revealed extensive plasma membrane blebbing,
      margination of condensed chromatin, and well-preserved organelles in these
      transfectants. The levels of TUNEL-positive cells, analyzed by a flow-cytometric
      method, were increased by four- to sevenfold in mutant APP transfectants, but
      less than twofold in wild-type APP transfectants relative to untransfected cells.
      Our results provide evidence that expression of mutant APPs in differentiated
      PC12 cells induces cell death via an apoptotic pathway.

PMID- 9039648
TI  - Normal temporal and spatial distribution of oligodendrocyte progenitors in the
      myelin-deficient (md) rat.
AB  - A point mutation in exon 3 of the proteolipid protein (PLP) gene of the myelin
      deficient (md) rat leads to a failure of oligodendrocyte maturation and early
      death of oligodendrocytes, resulting in dysmyelination. It has been suggested
      that an alternative-splice isoform of PLP, known as DM-20, might be expressed in
      oligodendrocyte progenitors in the embryonic central nervous system (CNS),
      raising the possibility that early development of the oligodendrocyte lineage
      might also be affected in the md rat. To test this suggestion, we visualized
      oligodendrocyte progenitors in the embryonic md rat spinal cord and brain by in
      situ hybridization with a probe to the platelet-derived growth factor alpha
      receptor (PDGFR). We could detect no abnormalities in the time of first
      appearance of oligodendrocyte precursors, nor in their subsequent proliferation
      and dispersal throughout the CNS. These data strongly suggest that the PLP
      mutation in the md rat primarily or exclusively affects the later stages of
      oligodendrocyte lineage.

PMID- 9039649
TI  - Involvement of protein kinase C in nerve growth factor- and K-252a-stimulated
      calcium uptake into PC12 cells.
AB  - Both nerve growth factor (NGF) and K-252a stimulate the uptake of calcium into
      PC12 cells. Stimulation by either is prevented by pretreatment of the cells with
      the tumor promoter phorbol 12-myristate 13-acetate (PMA), suggesting an
      involvement of protein kinase C in the stimulation. The effect of PMA is specific
      in that the calcium uptake stimulated by either the L-type channel agonist BAY K
      8644 or by ATP is not altered in PMA-pretreated cells. An involvement of kinase C
      is also suggested by the inhibition of NGF- or K-252a-stimulated calcium uptake
      by the kinase C inhibitors staurosporine and calphostin C. Inhibition by the
      isoform-specific agents GO 6976 and thymeleatoxin implicates one of the classic
      calcium-sensitive isoforms of kinase C. The close similarity in the profiles of
      inhibition of NGF-stimulated and K-252a-stimulated calcium uptake by the various
      effectors suggests that NGF and K-252a act on calcium uptake through some of the
      same signaling elements.

PMID- 9039650
TI  - Synergistic increase in nerve growth factor secretion by cultured vascular smooth
      muscle cells treated with injury-related growth factors.
AB  - Vascular smooth muscle (VSM) cells comprise one of the primary targets of the
      sympathetic nervous system and have been shown to secrete nerve growth factor
      (NGF). There is increasing evidence that changes in the levels of NGF in the
      adult may underlie certain pathological conditions. To investigate the potential
      role of altered NGF production in vascular disease, VSM cell cultures were
      treated with injury-related growth factors and the culture medium was assayed for
      NGF using a two-site enzyme-linked immunosorbent assay (ELISA). Platelet-derived
      growth factor (PDGF), a potent VSM mitogen, caused a dose-dependent increase in
      NGF secretion. After 4 hr, PDGF-treated cultures contained 10 times more NGF than
      control cultures. NGF release remained elevated for 48 hr, but the peak secretion
      occurred in the first 12 hr after treatment. Transforming growth factor beta (TGF
      beta) caused a fivefold increase in NGF at 4 hr when added alone, but synergized
      with PDGF yielding approximately 50 times more NGF than control cultures. TGF
      beta and epidermal growth factor (EGF) also displayed synergism. In contrast,
      basic fibroblast growth factor (bFGF), which had a modest effect alone, appeared
      to be additive with TGF-beta. Similarly, interleukin 1-beta (IL-1 beta), which
      mediates increased NGF synthesis in sciatic nerve lesions (Lindholm et al.:
      Nature 330:658-659, 1987), showed no synergism with TGF-beta.

PMID- 9039651
TI  - Differential expression of Na,K-ATPase alpha-isoform mRNAs in aging rat
      cerebellum.
AB  - Age-dependent changes in the expression of Na,K-ATPase alpha 1- and alpha 3-mRNAs
      were analyzed in the rat cerebellum by in situ hybridization. In young rats,
      alpha 1-mRNA showed prominent labeling in the granular layer (GL) with moderate
      fine distribution in the molecular layer (ML), Purkinje cell layer (PCL), and
      white matter (WM) but no clusters over Purkinje cells (PCs). In old rats, alpha 1
      mRNA remained unchanged in ML and PCL, but declined by 43% (P < 0.0001) in GL and
      increased by 624% (P < 0.0001) in WM. alpha 3-mRNA in young rats showed large
      clusters of label on stellate, basket, Golgi, and PCs and fine grains diffusely
      in ML, GL, and WM. In old rats, alpha 3-mRNA declined by 87% in ML, 83% in PCL,
      84% per PC, and 89% in GL and increased by 111% in WM (all values P < 0.0001)
      relative to young rats. PC numbers were reduced by 30%, but the average area of
      PC profiles did not change significantly. In old rats, the specific cluster-like
      label related to alpha 3-mRNA on PCs, stellate, basket, and Golgi cells was lost.
      Immunocytochemistry of cerebellum and hippocampus showed no age-related change in
      the distribution and density of total catalytic polypeptide. Thus, the
      discordance between changes in the levels of mRNAs in neuronal layers and WM in
      the face of constant polypeptide levels indicates age-related changes in
      polypeptide turnover. Cell- and isoform-specificity of alpha-isoform mRNAs in
      aging rat cerebellum may reflect differential regulation underlying age-related
      impairments in signal transduction and motor learning.

PMID- 9039652
TI  - Associations between intermediate filament proteins expressed in cultured dorsal
      root ganglion neurons.
AB  - The developmental profile of the neurofilament (NF) triplet proteins, alpha
      internexin and peripherin in cultured dorsal root ganglion neurons from gestation
      day 15 rat embryos was determined by Western blot analysis. At the outset (day 0
      in culture), the neurons contained mostly alpha-internexin. A significant
      increase in peripherin levels was seen at days 1-2, in the midsized (NFM) and low
      molecular weight (NFL) NF subunits at days 2-3, and in the high molecular weight
      (NFH) NF subunit at days 5-6. Immunofluorescence microscopy showed that the five
      intermediate filament proteins were co-localized in all neuronal cell bodies and
      neurites. Analysis of Triton X-100 extracts from okadaic acid-treated dorsal root
      ganglion cultures revealed that peripherin and alpha-internexin followed the same
      fragmentation pattern observed with NFs. Interactions between the various
      neuronal intermediate filament proteins in these extracts were assessed by
      immunoprecipitation under native conditions using antibodies specific for the
      individual proteins. Co-immunoprecipitation of NFH with NFL, NFM with NFL, NFM
      with alpha-internexin, and alpha-internexin with peripherin demonstrated that the
      intermediate filament cytoskeleton in cultured sensory neurons is a highly
      integrated structure.

PMID- 9039653
TI  - Kainate/AMPA receptors expressed on human fetal astrocytes in long-term culture.
AB  - Long-term cultivation of primary human fetal brain cells has yielded a
      homogeneous population of glial progenitors of extended life span. These human
      astrocyte precursor (HAP-1) cells have been in culture for greater than 1 year,
      are diploid, and do not form colonies in soft agar. The culture was established
      in 10% fetal calf serum (FCS), although cells greatly increase their
      proliferative rate when both basic fibroblast growth factor and FCS are present
      in the culture media. HAP-1 cells express the cytoskeletal proteins glial
      fibrillary acidic protein, vimentin, and nestin. HAP-1 cells express the
      AMPA/kainate receptor subunit genes GluRs 1, 3, and 4 and the kainate receptor
      subunit genes GluR6, KA1, and KA2. Immunohistochemistry confirms the expression
      of GluR subunit proteins. HAP-1 cells demonstrate a kainate-responsive current
      found to be blockable by CNQX. HAP-1 cells will serve in the study of human glial
      cells and ligand-gated ion channels and in the identification of compounds which
      might act as agonists or antagonists at these receptor-ion channel complexes.

PMID- 9039654
TI  - Differential expression in glial cells derived from chick embryo cerebral
      hemispheres at an advanced stage of development.
AB  - Recently, we have characterized glial cultures derived from very early
      neurogenesis (E3) and found them to consist largely of early glioblastic or
      astroblastic cells with the capacity to differentiate into astrocytes given
      sufficient time in culture or with advancing age, i.e., cell passage. This study
      examines and compares the characteristics of astrocyte-enriched cultures derived
      from advanced embryonic ages (E15) in the chick embryonic cerebral hemispheres.
      We report several remarkable findings. 1) Mature astrocytes (GFAP+, vimentin-)
      appear as early as 5 days in vitro (DIV) in primary culture (P0). 2) Also
      apparent in primary cultures were extensive populations of neurons
      (neurofilament+; NF+) growing atop or in close proximity to mature astrocytes. 3)
      NF+ neurons disappeared after the first cell passage, and GFAP+ astrocytes were
      greatly diminished within two cell passages thereafter. 3) High concentrations of
      NGF were expressed, presumably by glial cells, in primary cultures through 14
      DIV, declining to a low plateau through 27 DIV and remaining low, but measurable
      in subsequent cell passages. 4) At later cell passages (> 5) immature phenotypes
      of these same cell types continued to be expressed in E15CH cultures, i.e.,
      positive staining for GFAP and vimentin and GFAP, GS, and NGF can all be detected
      on Western blots. We conclude from these findings that 1) mitotic multipotential
      neural cells are present within cerebral hemispheres even at late stages of
      development (E15); 2) neuroblasts and astroblasts have a reciprocal relationship
      requiring the presence of both cell types in order for mature expression of their
      phenotypes; 3) the NGF profile parallels the appearance and disappearance of
      neurons in E15 chick embryonic cerebral hemisphere primary cultures, strongly
      suggesting that this trophic factor may be involved in the mutually beneficial
      relationship between astrocytes and neurons.

PMID- 9039655
TI  - Oligodendrocyte gene expression in the human fetal spinal cord during the second
      trimester of gestation.
AB  - A comprehensive evaluation of myelination during normal human development is
      essential to understand the pathology of congenital diseases of white matter. The
      present study establishes quantitative values for normal oligodendrocyte-specific
      gene expression during the early stages of myelination in the human fetal spinal
      cord. Complementary techniques of Northern and immunoblotting were used to
      determine relative amounts of oligodendrocyte-specific mRNAs and proteins between
      12 and 24 gestational weeks. Values were determined for myelin basic protein,
      2',3'-cyclic nucleotide 3'-phosphodiesterase, and proteolipid protein. The
      relative amount of myelin-associated glycoprotein mRNA was also estimated. To
      compare gene expression between glial cell types, the relative amounts of mRNA
      and protein were determined for glial fibrillary acidic protein (GFAP), a cell
      type specific marker for astrocytes. All oligodendrocyte-specific genes expressed
      similar developmental kinetics. Between 12 and 15 gestational weeks, less than a
      five-fold increase was detected in the expression of these genes and their
      protein products. Between 15 and 22 gestational weeks, the relative amounts of
      mRNA and protein for the myelin genes increased more than 80-fold. The kinetics
      of GFAP expression were similar to those of the myelin-associated genes. Absolute
      values for the increase in mass of the human fetal spinal cord were also
      obtained. These results provide data that may aid in the neuropathologic
      assessment and characterization of myelin disorders in the preterm, neonatal, and
      pediatric spinal cord.

PMID- 9039656
TI  - Delivery of liposome-sequestered hydrophobic proteins to lysosomes of normal and
      Batten disease cells.
AB  - We have developed a method to deliver hydrophobic proteins such as ATP synthase
      subunit c and ubiquitin to lysosomes of PMN (polymorphonucleocytes) and
      fibroblasts. ATP synthase subunit c is stored in the lysosomes of various tissues
      in late infantile and juvenile forms of neuronal ceriod lipofuscinosis, also
      called Batten disease (BD). Whether this protein storage is due to an
      abbreviation in protein or in the lysosomal hydrolases of BD is still not clear.
      We have sequestered this protein and ubiquitin in the lipid membrane of
      liposomes. The liposomes coated with autologous heat-aggregated IgG or
      apolipoprotein E when presented to the PMN and fibroblasts, respectively,
      accumulated in the lysosomes. Both normal and BD PMN degraded 125I-ubiquitin; the
      rate of degradation was, however, slower by Batten PMN. These studies indicate
      that a hydrophobic molecule such as subunit c can be delivered to PMN and
      fibroblasts, and the sequestered proteins are accessible to lysosomal hydrolases.
      Therefore, this technique can be used to study the metabolism of highly
      hydrophobic proteins by lysosomes, especially the biochemical mechanism(s) of
      subunit c storage in BD.

PMID- 9039658
TI  - Clinical approach still has an important role in constitutional bone diseases.

PMID- 9039659
TI  - Spondyloepiphyseal dysplasia with nephrotic syndrome (Schimke immunoosseous
      dysplasia).
AB  - We report a 3-year-old girl with the association of spondyloepiphyseal dysplasia,
      nephrotic syndrome, and signs of defective cellular immunity. The findings are
      similar to those reported by Spranger et al., which have become known as Schimke
      immunoosseous dysplasia.

PMID- 9039657
TI  - Deficient LAR expression decreases basal forebrain cholinergic neuronal size and
      hippocampal cholinergic innervation.
AB  - A role in neural development for protein tyrosine phosphatase (PTPase) receptors
      has been suggested by the finding of aberrant neurite outgrowth in Drosophila
      mutants lacking functional leukocyte common antigen-related (LAR) PTPase
      receptors; however, PTPase functions in the mammalian nervous system remain to be
      established. In transgenic mice containing a gene trap in the LAR gene, only
      trace expression of full-length LAR transcripts was found. In these mice, the
      size of basal forebrain cholinergic neurons was significantly reduced and
      cholinergic innervation of the dentate gyrus was markedly decreased. These
      findings constitute the first demonstration of an aberrant neuronal phenotype in
      a mammalian PTPase mutant and support the hypothesis that LAR-type PTPase
      receptors function to establish and/or maintain neuronal networks.

PMID- 9039660
TI  - Humero-spinal dysostosis: report of the fourth case with emphasis on generalized
      skeletal involvement, abnormal craniofacial features, and mitral valve
      thickening.
AB  - The fourth reported case of humero-spinal dysostosis is notable in that (a) it
      confirms the unique combination of bifid distal humeri and coronal clefts, (b)
      involves a third unique feature as being mitral valve thickening. (c) suggests a
      more generalized involvement of bone in the form of a dysplasia, and (d) raises
      the possibility of repetitive craniofacial features.

PMID- 9039661
TI  - Symmetrical enchondromatosis of the hands and feet in two sisters.
AB  - We report two Portuguese sisters aged 9 and 12 years with symmetric well
      circumscribed radiolucent cystic lesions on the long bone metaphysis of the hands
      and feet. The eldest also has soft tissue calcifications. They have no dysmorphic
      features and their growth is normal. Plasma values of parathyroid hormone (PTH),
      calcium, phosphorus, magnesium, and alkaline phosphatase are normal. Cerebral
      computed tomography (CT) scan shows no intracranial calcifications. A Raynaud
      phenomenon became evident during the last year in the eldest. The incisional
      biopsy of the left proximal metatarsial was performed through an area of typical
      radiographic appearance. The pathology specimen consisted of enchondroma tissue.
      The present cases are an extremely rare instance of this pathology, with
      symmetrical involvement of the hands and feet and a familial incidence.

PMID- 9039662
TI  - Rhizomelic chondrodysplasia punctata-like phenotype in a newborn male with normal
      peroxisomal function.
AB  - A newborn male with the characteristic phenotype of classic rhizomelic
      chondrodysplasia punctata (RCDP) and with the usual and severe radiographic
      skeletal abnormalities is described. The parents were young, healthy, and not
      consanguineous; the mother had not used licit or illicit drugs, alcohol, or
      tobacco during pregnancy and had not been exposed to radiation or teratogenic
      chemicals. The clinical phenotype led us to study peroxisomal function.
      Plasmalogen content in erythrocytes, membrane, and fibroblasts; dihydroxyacetone
      phosphate acyltransferase (DHAP-AT), alkyldehydroxyaceton phosphate synthetase (a
      gift from Professor Henk van der Boch, Utrech) in fibroblasts; and phytanic and
      pristanic acids in plasma showed normal values. Immunocytofluorescence study with
      antibodies against peroxisomal membrane showed normal organelles. We found no
      reference in the literature of a case of RCDP with normal peroxisomal functions,
      but non-CDP has been described with peroxisomal dysfunction. This phenotype
      (RCDP) may be due to other metabolic error.

PMID- 9039663
TI  - Brachytelephalangic chondrodysplasia punctata in a female child.
AB  - We report a case of a female child born to nonconsanguineous parents who at birth
      presents a facial dysmorphism including flattened and hypoplasic nose associated
      with epiphyseal stippling of the tarsal bones, the right hip, the cervical,
      lumbar, and sacral regions of the spinal column, and hypoplasia of the distal
      phalanges of the fingers. The current pregnancy history was negative for exposure
      to alcohol or drugs. The karyotype was normal. The clinical and radiological
      features strongly suggest brachytelephalangic chondrodysplasia punctata.
      Described in males, this condition has not previously been detected in a female;
      its gene has been assigned to Xp22.3. The present observation of
      brachytelephalangic chondrodysplasia punctata in a female questions the genetic
      heterogeneity of this syndrome.

PMID- 9039664
TI  - Acromesomelic dwarfism: a new variation.
AB  - The rate skeletal disorder, acromesomelic dwarfism, is characterized by short
      stature and short limbs. Bone dysplasia is evident. We report two cases of a
      variation of this disorder in a Portuguese woman and her son. The clinical
      features of these two cases differ from those of cases previously reported in the
      literature.

PMID- 9039665
TI  - Myositis ossificans: report of seven cases in children.
AB  - The clinical features of seven children with myositis ossificans (circumscripta
      and progressiva) and radiographic signs of the disease are described. We
      recommend systematic radiological examination to seek other skeletal
      malformations for congenital hallux valgus in young children, for it may be the
      first sign of a myositis ossificans progressiva. The "zone phenomenon" observed
      on histology, along with differential diagnosis and evolution, is documented. The
      necessity of a biopsy and different forms of treatment are discussed.

PMID- 9039666
TI  - Femoral callotasis.
AB  - The procedure for femoral callotasis is explained, and a series of 160
      lengthenings is reviewed, 60 for limb length discrepancy and 100 for short
      stature. Callotasis was performed in 106 subjects with a mean age of 19 years.
      The mean healing index (HI) of 36 days per centimeter is related more to etiology
      than to age or extent of lengthening. There were nine complications (15%) among
      subjects treated for limb discrepancies and 39 (39%) in those treated for short
      stature. Three permanent sequelae were recorded: necrosis of the head of the
      femur (two cases) and permanent extension deficit of the knee (one case). The
      present review assesses the type of results that can be achieved with callotasis
      in straightforward cases of femoral lengthening when the guidelines proposed by
      the author are followed. It does not attempt to compare this technique with other
      methods of limb lengthening.

PMID- 9039667
TI  - Acetabular notch.
AB  - Ultrasound images of dysplastic and/or unstable hips often display an indentation
      or notch at the superolateral part of the acetabulum where the iliac wing joins
      the acetabular roof. We reviewed the ultrasound and subsequent radiographic
      examinations of 295 babies examined in our hip screening clinic. Of the hips with
      a notch demonstrable at the first ultrasound, 97% had a persistent notch at the
      second ultrasound and in 79% the notch was apparent on the 3-month radiograph.
      When the notch persists, we believe that it represents damage to the lateral
      acetabular ring epiphysis and delayed maturation of the lateral acetabulum.

PMID- 9039668
TI  - Five additional cases of local fibrocartilaginous dysplasia.
AB  - Focal fibrocartilaginous dysplasia has previously been described as an etiology
      of genu varum deformity in children at about walking age. We have found 20 cases
      in the literature, and all of them were located in the medial proximal tibial
      metaphysis. We report five additional cases of this entity. The patients had a
      genu varum deformity, and the angulation was at the site of the bone lesion. Four
      cases were in the tibia, and one case was in the distal medial femoral
      metaphysis. Age at diagnosis ranged from 13 to 24 months. A cortical defect with
      surrounding sclerosis was observed on radiographs. The angulation usually
      progressed initially, and spontaneous resolution was observed in two cases at
      last follow-up. Open biopsy and tibial valgus osteotomy were performed in two
      cases. The unusual femoral case was also treated with open biopsy and medial
      hemicircumferential periosteal release. Spontaneous remodeling of varus
      angulation and resolution of bony defect may be expected in most cases, and
      osteotomy can be avoided.

PMID- 9039669
TI  - Nerves in human epiphyseal uncalcified cartilage.
AB  - Increasing evidence demonstrates clinical and neuroendocrine regulation of the
      skeletal system. We have demonstrated nerve fibers in cartilage canals in human
      fetal epiphyseal uncalcified cartilage. We investigated specimens from the femur,
      the proximal tibia, and the humerus from 12 human bodies with an age from the
      22nd gestational week to 13 months after birth. We performed Bodian silver
      staining, Kluver-Barrera staining, and immunostaining for neurofilaments, myelin
      basic protein. S-100 protein, and vimentin. We observed positive Bodian staining
      and immunoreaction to neurofilaments in all specimens older than the 30th week of
      gestational age. Myelin or Schwann cells could not be demonstrated, nor could
      mechanoreceptors. This indicates a traditional classification as type C nerve
      fibers with sensory or sympathetic function. In skeletal nerves, an increasing
      number of neuropeptides influencing bone cells has been detected. The nerves in
      the cartilage canals may have functions such as regulation of developmental or
      pathological processes.

PMID- 9039670
TI  - Early conservative and operative treatment to gain early normal growth in
      proximal femoral focal deficiency.
AB  - In three children with proximal femoral focal deficiency (PFFD), arthrography of
      the hip was performed at the respective ages of 9 days, 4 weeks, and 5 weeks.
      Between the unossified part of the femoral neck and the cartilaginous femoral
      head, there was moderate flexibility in the first child and lysis with some
      displacement of the femoral neck and mobility in the other two children. After
      the children's immobilization in a squatting cast for 3 months, consolidation was
      achieved and the growth plate developed normally. All three had marked coxa vara
      and retroversion. The earlier they were treated by valgus osteotomy and rotation
      to normal anteversion, the earlier normal growth started. Diagnosis at birth and
      immediate conservative and early operative treatment is therefore indicated in
      such cases. Only a few centimeters of femoral lengthening is then necessary, and
      resection of the unossified part of the femoral neck can be avoided.

PMID- 9039671
TI  - Keloid formation in syndactyly release: report of two cases.
AB  - The authors report rare keloid formation after syndactyly release in two white
      children. Resection and skin grafting were used to treat these patients with only
      moderate success.

PMID- 9039672
TI  - Traumatic proximal tibiofibular dislocation.
AB  - Proximal tibiofibular dislocation is an exceptional lesion. Rarer still is its
      presentation in childhood. We describe the clinical case of a 6-year-old boy, the
      victim of a road accident. He had a tibiofibular dislocation associated with a
      metaphyseal fracture of the tibia.

PMID- 9039673
TI  - Salmonella spondylitis.
AB  - We report a case of salmonella spondylitis in an adolescent without sickle cell
      disease or any history of salmonella gastroenteritis. The infecting organism
      (cultured from material aspirated from the bone lesion) was Salmonella enterica
      serovar Newport. With nonoperative treatment, evolution was favorable.

PMID- 9039691
TI  - In vivo inhibition of the regenerative capacity of hydatid material after
      treatment with netobimin.
AB  - The effect of netobimin and netobimin plus fenbendazole administration on
      secondary hydatid disease was studied. Secondary hydatid disease in gerbils
      (Meriones unguiculatus) was produced by intraperitoneal inoculation of
      protoscolices of Echinococcus granulosus. The experimental animals received doses
      of 20 and 50 mg/kg of netobimin or a mixture of netobimin and 1.7 mg/kg of
      fenbendazole. The results showed that after a single dose of netobimin at the
      studied concentrations, the cystic material transplanted into the mouse produced
      a significant recurrence of the disease, but the most remarkable finding was that
      the hydatid-cyst recurrence never took place when netobimin was given together
      with fenbendazole.

PMID- 9039692
TI  - Distribution of mast cells and their correlation with inflammatory cells around
      Onchocerca gutturosa, O. tarsicola, O. ochengi, and O. flexuosa.
AB  - In recent years, bovine Onchocerca species have been used as models for human
      onchocerciasis in drug screens. They have been suggested for immunology studies
      and evaluation of vaccine candidates. Therefore, mast cells and their association
      with other inflammatory cells were studied in five onchocercal species of cattle
      and deer using immunohistology. Intact mast cells occurred in large numbers in
      the capsule and septae of nodules, in fibrous tissue adjacent to nonnodular
      worms, and perivascularly. Inactive and, more frequency, activated and
      degranulating mast cells were observed within infiltrates in the nodule center or
      around nonnodular filariae. They were not detected in direct contact with the
      cuticle of adult worms or of microfilariae or among the macrophages, giant cells,
      and neutrophils forming the innermost layer around the worms. Eosinophils, but
      not mast cells, were obviously associated with microfilariae-producing females.
      The distribution, frequency, and activity of mast cells were similar for all five
      species and O. volvulus.

PMID- 9039693
TI  - Recovery of waterborne oocysts of Cryptosporidium from water samples by the
      membrane-filter dissolution method.
AB  - The cellulose-acetate membrane (CAM)-filter dissolution method implemented into a
      Millipore Glass Microanalysis system was used for recovery of Cryptosporidium
      parvum oocysts seeded into 25 l of drinking water in polyethylene carboy
      aspirator bottles. CAM-entrapped oocysts were detected by immunofluorescence
      microscopy. From 65 to 94 oocysts/l (mean 75 oocysts/l), 34.7% overall of the
      inoculated oocysts, were unrecovered as determined after the water had been
      drained from the bottle, rinsed with 1 l of eluting fluid (EF), and CAM-filtered.
      Efficiency rates of oocyst recovery ranged from 24.0% to 64.0% (mean 44.1%),
      without the use of EF and from 72.1% to 82.3% (mean 78.8%) when EF was used. To
      ensure a high recovery efficiency of Cryptosporidium oocysts from sampled water
      by the CAM-filter dissolution method, it is recommended that 1 l of EF per 25 l
      of water be used.

PMID- 9039694
TI  - Ultrastructure and cytochemistry study of Eimeria sparis (Protozoa:Apicomplexa)
      stages from the intestine of gilthead sea bream Sparus aurata L.
      (Pisces:teleostei).
AB  - The ultrastructure and cytochemistry of merogonial, gamogonial, and early
      sporogonial stages of Eimeria sparis in the intestine of Sparus aurata were
      studied. Mature stages showed the typical pellicle, which was lost in some
      transitional stages. An apparent unit membrane was seen in some immature stages.
      A parasitophorous vacuole, sometimes with membrane vesicular invaginations, was
      usually observed. We propose that the stages located over the epithelium and the
      so-called epicellular stages be termed supraepithelial stages. Endomerogony was
      observed in intraepithelial and supraepithelial positions. Intraepithelial stages
      apparently starting ectomerogony were also detected. Electron-dense granules
      similar to wall-forming-like bodies of types 1 and 2 were observed. Microgametes
      exhibited two flagella. Cytochemistry study revealed scarce polysaccharides, if
      any, in merogonial stages and in microgamonts. The occurrence of polysaccharides
      and amylopectin granules increased progressively in macrogamonts, macrogametes,
      zygotes, and early oocysts. Lipidic droplets were scarce of absent in merogonial
      stages and abundant in maturing macrogamonts. Some glycoproteins were
      demonstrated in certain merogonial stages.

PMID- 9039695
TI  - Litomosoides chagasfilhoi sp. nov. (Nematoda:Filarioidea) parasitizing the
      abdominal cavity of Akodon cursor (Winge, 1887) (Rodentia:Muridae) from Brazil.
AB  - Litomosoides chagasfilhoi sp. nov., a parasite of the abdominal cavity of the
      wild rodent Akodon cursor (Winge. 1887), is described herein according to
      investigations conducted by light and scanning electron microscopy. The leading
      morphological characteristics of the new species are as follows: the buccal
      capsule is higher than it is wide and has walls thinner than the lumen, and the
      left spicule presents a handle longer than the blade, whose edges from large
      membranous wings folded longitudinally. This new species is different from L.
      silvai Padilha and Faria, 1977, living in the thoracic cavity of the same host.

PMID- 9039696
TI  - Alpha-2-macroglobulin binds to the surface of Trypanosoma cruzi.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, infects vertebrate
      cells after an initial step of parasite/host-cell recognition. Alpha-2
      macroglobulin (A2M), an important type of physiological proteinase inhibitor
      found in tissues and in the plasma of mammals, inhibits cell invasion by T. cruzi
      and accumulates in sites of the inflamed myocardium associated with parasite
      antigens. To study whether A2M would bind to T. cruzi, an indirect
      immunofluorescence reaction was performed using two different anti-mouse A2M
      sera. Intense labeling was observed in the membrane lining the cell body and the
      flagellum of bloodstream trypomastigotes obtained from experimentally infected
      mice in the peak of parasitemia, suggesting that the antisera recognize plasma
      A2M associated with the parasite surface. Metacyclic trypomastigotes obtained in
      a serum-free defined medium reacted with anti-A2M only after previous incubation
      with purified human A2M. Enzyme-linked immunosorbent assay (ELISA) studies were
      applied to characterize better the binding of native (N-A2M) and of proteinase
      complexed (P-A2M) forms of A2M. The "in vitro" binding of N-A2M to
      trypomastigotes was better at pH 5.0, followed by pH 10.0 and pH 7.4. Cysteinly
      and serine proteinase inhibitors, E-64 and STI, respectively, inhibited the
      reaction. P-A2M also bound to T. cruzi in a dose-dependent way. Flow-cytometry
      studies showed that about 80% of the parasites stained with fluorescein
      isothiocyanate (FITC)-labeled P-A2M (50 micrograms/ml) with high affinity at pH
      7.4 (but also at pH 10.0) in a process that was reverted by the addition of
      unlabeled P-A2M or the calcium-chelator agent EDTA and also by incubation at an
      acid pH (4.0). These results suggest that (a) native-A2M binds to T. cruzi
      proteinase(s) and (b) T. cruzi expresses a receptor(s) that binds proteinase
      complexed A2M.

PMID- 9039697
TI  - A transformation vector for stage-specific expression of heterologous genes in
      Trypanosoma cruzi epimastigotes.
AB  - To express heterologous genes in a stage-specific manner, we constructed a
      transformation vector for Trypanosoma cruzi containing a selection gene (hyg) and
      a reporter gene (luc) flanked by sequences of the multicopy 1f8 gene arranged so
      as to provide a trans-splicing acceptor site to hyg and a putative
      polyadenylation signal to luc. The intergenic region of the T. cruzi genes 294
      and KAP was placed between hyg and luc, contributing the polyadenylation signal
      of 294 to hyg and the KAP trans-splicing acceptor site to luc. Transformation was
      carried out by electroporation, and transformed epimastigotes were selected in
      medium containing hygromycin B. Through double homologous recombination of the
      1f8 sequences with their chromosomal counterparts, the construction is inserted
      into the 1f8 locus, substituting probably one and no more than a few copies of
      the 1f8 gene without having apparent deleterious effects on the parasite. cDNA
      analysis demonstrated that the introduced signals were correctly processed,
      resulting in translatable hyg and luc mRNAs. Whereas epimastigotes express
      luciferase, no expression is found in the trypomastigote stage.

PMID- 9039698
TI  - Investigation of different ontogenetic stages of Raillietiella sp.
      (Pentastomida:Cephalobaenida): the embryonic gland--glandula embryonalis--or
      dorsalorgan.
AB  - The "Dorsalorgan" of pentastomids is an embryonic gland. With respect to a
      general revision of the glandular equipment of pentastomids and its synonyms the
      term embryonic gland, first mentioned by Esslinger in 1968, or glandula
      embryonalis (original) appears to be most suitable. Thus, this terminology may no
      longer lead to confusion of these glands with dorsal organs of other arthropods.
      The ultrastructure of the embryonic gland and its role within the development of
      the embryonic envelopes of the pentastomid genus Raillietiella is described
      herein for the first time. The embryonic gland is composed of numerous secretory
      cells, which are arranged concentrically around a bottle-shaped cavity. The cells
      of the neck region produce an extracellular supporting layer to stabilize the
      collar. The basal cells are characterized by numerous microvilli, secreting mucus
      into the cavity. The product of the embryonic gland is secreted between the zona
      radiata externa/interna and the blastoderm cuticle, respectively. The embryonic
      gland disintegrates before larval hatching.

PMID- 9039699
TI  - Assessment of the viability of Schistosoma mansoni schistosomula by comparative
      uptake of various vital dyes.
AB  - Of various vital dyes used to assess schistosomula viability, toluidine blue
      enabled differential counting of the schistosomula on microscope slides but not
      in culture wells, whereas methylene blue could be added directly to the
      schistosomula suspension in culture wells of microtiter plates. Toluidine blue
      uptake by dead parasites was very fast. It mostly also partially stained damaged
      but not dead organisms. Its main disadvantage was rapid, nonspecific staining of
      live schistosomula, requiring prompt counting of a preparation and additional
      reliance on motility for assessment of viability. Methylene blue staining of dead
      worms was slower, but it did not stain the live worms until about 1 h after dye
      application, enabling its addition to a series of preparations for consecutive
      counting. It did not always stain flattened, dead schistosomula or it stained
      them an uncontrasting pale blue. This dye remarkably induced movement in
      seemingly inert and probably damaged worms, thus enabling determination of
      viability even following poor staining or a lack of staining.

PMID- 9039700
TI  - In vivo and in vitro experimental intestinal amebiasis in Mongolian gerbils
      (Meriones unguiculatus).
AB  - One of the main drawbacks of experimental amebiasis is the lack of an adequate
      animal model for invasive intestinal lesions. Mongolian gerbils are useful
      because both intestinal and hepatic amebiasis can be produced experimentally with
      Entamoeba histolytica trophozoites. In this paper we show results obtained with
      in vivo and in vitro models of intestinal amebiasis in gerbils. We inoculated
      gerbils intracecally with monoxenic cultures of a highly virulent E. histolytica
      HM1:IMSS substrain. In the in vivo model an increase in mucus production was
      observed during the first 6 h of interaction. Microulcerative mucosal lesions
      appeared at 24-72 h postinoculation. Inflammatory infiltrate and edema of the
      lamina propria were associated with superficial foci of necrosis. At 96 h the
      cecal mucosa had an almost normal appearance and live amebas were no longer
      detected. In the in vitro model, early damage was detected in cecal strips
      mounted in Ussing chambers as a rapid fall in potential difference, short-circuit
      current, and transepithelial resistance that correlated with the extent of the
      microscopic lesions produced. The latter consisted of cellular edema and the
      appearance of small, translucent vacuoles at the base of epithelial cells.
      Further damage led to loss of intercellular junctions, destruction of
      interglandular epithelial cells, and edema of the lamina propria. The present
      results demonstrate that the gerbil is useful as an experimental model for the
      analysis of early stages of invasive intestinal amebiasis both in vivo and in
      vitro.

PMID- 9039701
TI  - Light and electron microscopy study of carbohydrate antigens found in the
      electron-lucent layer of Pneumocystis carinii cysts.
AB  - The localization and biochemical nature of antigens found in the electron-lucent
      layer (ELL) of Pneumocystis carinii cysts using polyclonal rabbit antibodies are
      described. These antigens, specific for the cystic stages of the parasite, were
      shared by organisms from different hosts, suggesting that they represent
      functionally important components of the cyst cell wall. The binding sites were
      situated on an interwoven net of fibrils in the ELL produced by mild to strong
      proteolysis. Degradation of this residue by glucanase and chitinase confirms that
      this layer contains branched glucan and chitin. In contrast, the prompt
      susceptibility of the polysaccharide-rich ELL to proteolysis reveals that
      proteins are also relevant in building up the cyst-wall glucan skeleton. It is
      therefore concluded that the formation of the Pneumocystis cyst wall shows
      differences to the typical fungal cell-wall architecture. The taxonomical debate
      regarding this unique protist is ongoing, and consideration of these
      immunological and morphological findings may be useful for the study of the
      biology and phylogeny of Pneumocystis.

PMID- 9039702
TI  - Tryptophan-N-formylated gramicidin causes growth inhibition of Plasmodium
      falciparum by inducing potassium efflux from infected erythrocytes.
AB  - In a study of the supposed selective action of tryptophan-N-formylated gramicidin
      (NFG) on infected erythrocytes as well as the relationship between the ability of
      NFG to inhibit parasite growth and its capacity to induce potassium leakage from
      infected cells, a series of experiments was performed in which in vitro cultures
      of Plasmodium falciparum were incubated with NFG or gramicidin. Those cultures
      were subsequently assayed for intracellular sodium and potassium contents, cell
      lysis, and/or parasite viability. It is shown and discussed that although NFG can
      attack both infected and uninfected erythrocytes, resulting in potassium efflux
      from and sodium influx into these cells, the effects are much greater on infected
      erythrocytes than on uninfected ones. Furthermore, the results strongly suggest
      that NFG-mediated potassium efflux is the direct cause of parasite death.

PMID- 9039703
TI  - Chemoattraction and penetration of Echinostoma trivolvis and E. caproni cercariae
      in the presence of Biomphalaria glabrata, Helisoma trivolvis, and Lymnaea elodes
      dialysate.
AB  - A petri-dish bioassay was used to study the chemoattraction and penetration of
      the cercariae of Echinostoma trivolvis and E. caproni in the presence of snail
      dialysates from Helisoma trivolvis (Pennsylvania and Colorado strains).
      Biomphalaria glabrata, and Lynmaea elodes. Significant chemoattraction was seen
      with E. trivolvis cercariae in the presence of all snail dialysates released from
      nonperforated dialysis sacs with a molecular-weight exclusion of 12,000. Under
      the same conditions, E. caproni was significantly attracted to B. glabrata and H.
      trivolvis (CO strain) but not to L. elodes or H. trivolvis (PA strain). Dialysis
      sacs were perforated with needles to allow the release of snail substances of all
      molecular weights into the bioassay. Cercariae of both species were significantly
      attracted to all snail dialysates released from perforated sacs. Moreover,
      cercariae entered these sacs and penetrated the snails, and 24 h later the
      percentage of cysts per snail species ranged from 70% to 83% for E. trivolvis and
      from 73% to 93% for E. caproni. Dialysates released from intact sacs were
      extracted in choloroform-methanol (2:1) to obtain hydrophilic and lipophilic
      fractions. When these extracts were placed on agar plugs in the bioassay, the
      lipophilic fraction, but not the hydrophilic fraction, was mainly
      chemoattractive.

PMID- 9039704
TI  - Biochemical alterations in paromomycin-treated Leishmania donovani promastigotes.
AB  - Paromomycin is used for the treatment of leishmaniasis in humans, but little is
      known about its mechanism of action. Investigating the effect of this antibiotic
      on promastigotes of Leishmania donovani, we showed that inhibition of the
      multiplication of these parasites could be related to its effect on RNA synthesis
      and to modifications of membranous polar lipids and membrane fluidity, leading to
      altered membrane permeability.

PMID- 9039705
TI  - Efficacy of some pyrethroids against a strain of the rabbit ear mite (Psoroptes
      cuniculi): an unusual cross-resistance pattern.
AB  - An in vitro immersion bioassay was used to compare the efficacy of selected
      pyrethroids against a deltamethrin-resistant strain of rabbit ear mite (Psoroptes
      cuniculi). A lack of cross-resistance between bromo (deltamethrin) and chloro
      analogues (cypermethrin) of alpha-cyano-3-phenoxybenzyl-dihalovinyl
      dimethylcyclopropane carboxylate was detected. Whereas deltamethrin proved to be
      inactive (48-h mortality 21.9% at 1000 mg/kg), each cypermethrin isomer mixture
      tested, including alpha-cypermethrin [IR(cis) alpha S + 1 S (cis) alpha R] and
      theta-cypermethrin [1R(trans) alpha S + 1 S (trans) alpha R] and their mixture at
      a ratio of 4/6, beta-cypermethrin, showed high efficiency (48-h mortality > or =
      95% at 1000 mg/kg).

PMID- 9039706
TI  - Cloning and characterization of elongation factor 1-alpha of Schistosoma mansoni.

PMID- 9039707
TI  - Chromatographic analysis of water and wine samples for phenolic compounds
      released from food-contact epoxy resins.
AB  - Food-contact epoxy resins can release phenolic compounds such as phenol, m
      cresol, bisphenol F, bisphenol A, 4-tert-butylphenol, bisphenol F diglycidyl
      ether (BFDGE), and bisphenol A diglycidyl ether (BADGE) into foodstuffs. A
      validated high-performance liquid chromatographic method with fluorometric
      detection is described for the simultaneous analysis of these compounds in wine
      and mineral water. Sample preparation by solid-liquid extraction enables
      detection limits of 2.5 micrograms/L in wine and 0.25 microgram/L in mineral
      water to be achieved. Recovery rates are close to 100%, except for BFDGE and
      BADGE (around 60% in wine and 75% in mineral water).

PMID- 9039708
TI  - Studies on neurosteroids. V: Separation and characterization of pregnenolone 3
      stearate in rat brains using high-performance liquid chromatography.
AB  - The separation and characterization of pregnenolone 3-stearate in rat brains are
      carried out using high-performance liquid chromatography (HPLC). The pregnenolone
      3-stearate is obtained from a whole rat brain by extraction with ethyl acetate
      followed by silica gel column chromatography. The obtained fraction is
      derivatized with 1-dimethylaminonaphthalene-5-sulfonylhydrazine (dansylhydrazine)
      or 4-(N,N-dimethylaminosulfonyl)-7-hydrazino- 2,1,3-benzoxadiazole, and the
      derivative is separated by successive preparative HPLC with fluorescence
      detection. The chromatographic behaviors of both derivatives are identical to
      those of authentic samples. The former derivative obtained from the rat brain
      shows satisfactory mass spectral data, and after hydrolysis, dansylpregnenolone
      is confirmed by HPLC.

PMID- 9039709
TI  - Healthcare for the millennium: can we prevent a funding nightmare?

PMID- 9039710
TI  - Cigarette deaths, cigarette advertisements, cigarette recruits, cigarette money.

PMID- 9039711
TI  - How do general practitioners manage patients at risk from stroke?
AB  - This study assessed by means of a postal questionnaire how general practitioners
      (GPs) manage patients at risk from stroke. Of the 640 GPs sent a questionnaire,
      294 (46%) replied. In patients with a recent transient ischaemic attack or minor
      ischaemic stroke, 24% of responding GPs would not arrange any investigations.
      Sixty-one per cent refer under half of their patients for further investigation,
      although 99% of GPs would commence aspirin. Seventy-seven per cent of GPs were
      aware of the benefits of carotid surgery. For patients in atrial fibrillation,
      most GPs (77%) thought that warfarin reduced stroke rates, but only 20% would
      consider commencing warfarin, although 26% would commence aspirin. In
      hypertensive patients, the GPs' threshold for treatment ranged from 135 to
      200mmHg systolic (median 160mmHg), and from 90 to 110mmHg diastolic (median
      100mmHg). Most GPs (84%) would treat isolated systolic hypertension with a median
      threshold of 180mmHg (range 140-240mmHg). The results of this study suggest that
      some patients at risk from stroke may not receive optimal investigation and
      treatment in the community.

PMID- 9039712
TI  - Is hormone replacement therapy prescribed for postmenopausal diabetic women?
AB  - A community-based survey was undertaken to ascertain current hormone replacement
      therapy (HRT) prescription rates in postmenopausal diabetic women. From age/sex
      and disease registers linked to prescription data which covered 144,237 patients,
      details on 6867 women aged 50-60 years were obtained. Of this group, 1684 (24.5%)
      were receiving prescriptions for HRT; the comparable figures for the 537 patients
      with hypertension and 135 (insulin-dependent and non-insulin dependent) diabetic
      patients were 117 (21.8%) and 15 (11.1%) respectively. While the presence of
      hypertension did not affect the likelihood of being prescribed HRT (odds ratio
      0.85 [95% CI 0.68-1.05], p > 0.1), women with diabetes were less than half as
      likely as those from the general population to be prescribed HRT (odds ratio 0.38
      [95% CI 0.21-0.67], p < 0.001). These data indicate that proportionately greater
      numbers of postmenopausal diabetic women, even compared with those with
      hypertension, another group at high risk of cardiovascular disease, are denied
      the potential benefits of HRT.

PMID- 9039713
TI  - A study of lipid profile before and after coronary artery bypass grafting.
AB  - This study was undertaken to establish the variability in the levels of total
      cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL)
      cholesterol, and high-density lipoprotein (HDL) cholesterol before and after
      coronary artery bypass graft (CABG) surgery, in order to determine
      postoperatively when an accurate assessment can be made of the lipid status.
      During a prospective study over 4 months, fasting venous samples were taken pre-
      and postoperatively on day 5, and in the 4th, 8th and 12th weeks. Ninety-six
      patients admitted to the cardiothoracic and cardiac wards for CABG were recruited
      to the study. The mean preoperative levels were: TC 5.94 (+/- 0.1 mmol/l), LDL
      cholesterol 4.02 (+/- 0.09mmol/l) and HDL cholesterol 1.00 (+/- 0.03mmol/l).
      These were significantly different (p < 0.01) from the levels on the 5th
      postoperative day when the mean level of TC was 4.14 (+/- 0.084mmol/l), LDL
      cholesterol was 2.45 (+/- 0.07mmol/l) and HDL cholesterol was 0.74 (+/-
      0.03mmol/l). By the 4th postoperative week, mean TC (5.73 +/- 0.13mmol/l), LDL
      cholesterol (3.79 +/- 0.14mmol/l) and HDL cholesterol (1.03 +/- 0.04mmol/l) did
      not vary significantly from the mean preoperative values. There was no
      significant difference in the mean TG levels pre- and postoperatively. The mean
      TC, LDL cholesterol and HDL cholesterol rise to preoperative levels by the 4th
      week after CABG. Thus, an accurate assessment of patients' lipid status can be
      made from this period. An earlier postoperative assessment may be falsely
      reassuring.

PMID- 9039714
TI  - Allergic reactions to local glyceryl trinitrate administration.
AB  - To assess the exact cause and extent of transdermal glyceryl trinitrate (GTN)
      induced allergic reactions, a study of continuous and intermittent use of GTN
      patches was conducted in 320 patients with New York Heart Association (NYHA)
      class II and III angina pectoris. Three commercially available GTN patch systems
      were used. Twenty-one patients (6.5%) developed cutaneous reactions. In 17
      patients (5.3%), the reactions were confined to the area of application and were
      characterised as irritant reactions. Four patients (1.2%) developed both
      localised and remote from the area of application lesions and one patient
      developed a generalised anaphylactic reaction. The rate of discontinuation of
      therapy was 3.4%. The irritant skin reactions were mainly due to contaminants and
      additives. Changing to a different transdermal system reduced the incidence of
      local reactions--a particularly desirable effect in patients who respond well to
      GTN therapy.

PMID- 9039715
TI  - Seventy-two hour comparison of methylprednisolone suleptanate and
      methylprednisolone sodium succinate in patients with acute asthma.
AB  - The efficacy and safety of the methylprednisolone prodrugs methylprednisolone
      suleptanate and methylprednisolone sodium succinate were evaluated in a
      multicentre, randomised, double-blind, double-dummy parallel study of 88 patients
      hospitalised with acute asthma. Each study drug was administered as a bolus
      intravenous injection of 40mg methylprednisolone equivalents every 6 hours for 48
      hours. Methylprednisolone 32mg was administered orally 6 hours after the last
      dose. Pulmonary function, medical events, and clinical laboratory values were
      assessed at predefined intervals before and during the 72-hour study. The primary
      response measure of pulmonary function was per cent predicted forced expiratory
      volume in one second (FEV1) at 48 hours. Secondary response measures were peak
      expiratory flow rate (PEFR) and FEV1/forced vital capacity (FVC) ratio. Although
      both drugs demonstrated within-group mean changes from baseline (starting at 6
      hours) that were statistically significant for each response, there were no
      statistically significant differences between the two groups. The mean percent
      predicted FEV1 at 48 hours and mean per cent change from baseline were 64% and
      13% (p < 0.0001) for the methylprednisolone suleptanate group and 67% and 17% (p
      < 0.0001) for the methylprednisolone sodium succinate group, respectively. The
      mean PEFR and FEV1/FVC ratio at 48 hours were 5.77 l/s and 73% for the
      methylprednisolone suleptanate group and 5.78 l/s and 76% for the
      methylprednisolone sodium succinate group, respectively. There were no clinically
      or statistically significant between-group differences in any of the safety
      parameters. In this study, methylprednisolone suleptanate and methylprednisolone
      sodium succinate have been shown to be therapeutically equivalent in the
      treatment of patients hospitalized with acute asthma.

PMID- 9039716
TI  - The duration of action of inhaled formoterol dry powder.
AB  - The duration of action of formoterol inhaled as a dry powder formulation is
      compared with placebo and a reference treatment of salbutamol dry powder in
      patients with bronchial asthma. This single-centre, double-blind, cross-over
      study recruited 23 outpatients with clinically stable asthma. These patients were
      treated with 12 micrograms formoterol, 400 micrograms salbutamol or placebo in a
      randomly allocated sequence, with at least 2 days between treatments. Forced
      expiratory volume in 1s of expiration (FEV1) was measured at specified time
      points from 15 min to 15 hours post-treatment. Formoterol produced significantly
      higher values of FEV1 at the primary endpoint of 12 hours compared with placebo
      and salbutamol. No differences between FEV1 values were seen for the active
      treatments of formoterol and salbutamol for the first 5 hours post-inhalation.
      Formoterol was significantly superior to placebo at all time points, whereas
      salbutamol was significantly superior to placebo for the first 5 hours. This
      study demonstrates that formoterol, when given as a dry powder inhalation, has a
      significantly longer duration of acute bronchodilator action than 400micrograms
      salbutamol inhaled as a dry powder. The duration of action of formoterol of at
      least 12 hours seen in this study is at least as long as that reported following
      administration from a metered dose inhaler (MDI) at the same dose level. The
      study also demonstrates that 12micrograms formoterol dry powder is well tolerated
      by patients.

PMID- 9039717
TI  - Bone mineral density in premenopausal women with oestrogen deficiency and
      symptomatic coronary heart disease.
AB  - Serum oestrogen deficiency is one of the main causes of osteoporosis in post
      menopausal women. In premenopausal women, oestrogen deficiency is rare. In 13
      premenopausal women with symptomatic coronary heart disease (CHD) and
      significantly reduced serum oestrogen levels, bone mineral density, determined by
      quantitative computed tomography (QCT), was not reduce. In these women, oestrogen
      deficiency was probably one risk factor for the development of CHD. The level of
      serum oestrogen that protects women from the development of CHD might be
      different from the level that protects them from early loss of bone mineral
      density. Seven of the 13 women had a history of tubal sterilisation. This might
      be a possible risk factor, causing ovarial dysfunction and oestrogen deficiency.

PMID- 9039718
TI  - Fixed dose combinations of ACE inhibitors.
AB  - First-line antihypertensive monotherapy is effective in reducing blood pressure
      to within the normal range in approximately 50% of patients. Normalisation in the
      remaining patients may require a combination of two or more drugs. This review
      considers the clinical efficacy and tolerability of combinations involving
      angiotensin-converting enzyme (ACE) inhibitors. The efficacy of combinations with
      diuretics or calcium antagonists, as initial therapy or in patients with
      inadequate responses to monotherapy, has been demonstrated in many trials. With
      combination therapy, normalisation rates approaching 80% can be achieved using
      submaximal doses of both components. Therapy with both combinations is well
      tolerated; with ACE inhibitors reducing the diuretic metabolic effects or
      counteracting some calcium antagonist-associated vasodilatory effects. Data on
      ACE inhibitors with beta-blockers are limited. When patients respond inadequately
      to first-line monotherapy, the increasing availability of drug combinations will
      allow individual selection of the most appropriate combination, taking account of
      additional risk factors and concomitant disease.

PMID- 9039719
TI  - Are intravenous cannulae still being misused?
AB  - We have surveyed the use of intravenous cannulae (IVC) in a district general
      hospital. Of 354 patients interviewed on various wards, 125 (35.3%) had IVC in
      situ. The wrist was the commonest location for the cannulae (41.6%). An
      indication for cannula insertion was present in the majority (93.7%) of patients.
      Cannulae were left in situ even after their use had ceased, most commonly on
      wards for the elderly, and on these wards complications were more common. Other
      wards had specific IVC documentation, which resulted in fewer complications.
      Cannulae should be used for specific indications and should be reviewed daily for
      the development of complications and the need for their continued presence.

PMID- 9039720
TI  - Limitations of typhoid vaccination for travellers.
AB  - Around one-third of travellers to endemic areas receive pre-travel typhoid
      vaccination, increasingly with the new parenteral vaccination Typhim Vi
      (Merieux). More than 200 cases of Salmonella typhi and S. paratyphi infection are
      imported into the UK each year. Despite the widespread use of immunisation, non
      specialist clinicians and the travelling public do not appear to fully appreciate
      the limitations of currently available vaccination. These limitations are not
      adequately highlighted in either the Green Book of Immunisation against
      Infectious Diseases (HMSO, 1992) or the new handbook Health Information for
      Overseas Travel (HMSO, 1995) which are important sources of reference for
      clinicians and practice nurses. This may delay consideration of diagnosis and
      presentation for treatment in immunised travellers.

PMID- 9039721
TI  - Variations of invasive Salmonella infection in elderly people.
AB  - Four cases of elderly people with differing forms of invasive salmonella
      infection are presented. Vulnerability factors and patterns of presentation are
      discussed.

PMID- 9039722
TI  - An unusual thyroglossal cyst causing upper airway obstruction.
AB  - Rarely does a thyroglossal cyst reach such proportions as to compromise the upper
      respiratory airway. Such a case is presented and the manner in which it was
      satisfactorily treated is described.

PMID- 9039723
TI  - Aneurysmal bone cyst of the clavicle in a child.
AB  - We report a case of an aneurysmal bone cyst (ABC) of the clavicle in a 9-year-old
      boy, which initially presented as a pathological fracture of a benign cystic
      lesion. ABC of the clavicle is rare in children less than 10 years old and
      radiological diagnosis may prove difficult in the early stages of presentation.

PMID- 9039724
TI  - Fentanyl therapy controls autonomic hyperactivity in tetanus.
AB  - This report describes the use of fentanyl in severe tetanus after failure of
      established therapeutic modalities (heavy sedation, neuromuscular blockade and
      ventilation). Cardiovascular instability accompanying severe tetanus secondary to
      sympathetic overactivity and raised catecholamine levels is associated with a
      mortality of over 50%. In this clinical situation, a variety of drugs with a
      primary or secondary action on the cardiovascular system has been used with
      varying success. The following case of severe generalised tetanus in the adult
      associated with autonomic hyperactivity, was successfully managed with large
      doses of intravenous fentanyl.

PMID- 9039725
TI  - Cancer in children. Introduction.

PMID- 9039726
TI  - Geographic and ethnic variations in the incidence of childhood cancer.
AB  - The total incidence of childhood cancer varies rather little between different
      regions of the world, with cumulative risk to age 15 nearly always in the range
      1.0-2.5 per thousand. Acute lymphoblastic leukaemia, especially in early
      childhood, is most common in populations of high socio-economic status and is the
      most frequent childhood cancer in all industrialised countries. The risk of
      Burkitt's lymphoma is highest in tropical Africa and Papua New Guinea; it is
      strongly associated with Epstein-Barr virus infection and intense immune
      stimulation by malaria. Other lymphomas are also relatively common in developing
      countries. Non-heritable retinoblastoma has a higher incidence among less
      affluent populations, suggesting an association with poor living conditions and
      maybe an infectious aetiology. In contrast, the incidence of Wilms' tumour and
      Ewing's sarcoma varies largely on ethnic lines, indicating a strong role for
      genetic predisposition. Much of the variation in recorded incidence of brain
      tumours and neuroblastoma may be due to varying levels of case ascertainment.
      Recently the incidence of childhood Kaposi's sarcoma has risen substantially in
      parts of Africa severely affected by the AIDS epidemic.

PMID- 9039727
TI  - Genetics of childhood cancer.
AB  - In the last 5 years, there has been a tremendous increase in understanding of the
      molecular genetics of several childhood cancers. The genes for more than 10
      cancer predisposition syndromes are now cloned and the molecular basis of their
      functioning is being analysed. The classical model of inherited cancer
      predisposition being due to mutation of tumour suppressor genes is being expanded
      to include genes involved in DNA processing and weakly dominant oncogenes. The
      chromosomal translocation characteristic of specific types of sporadic tumours
      are yielding to the molecular knife, with the isolation of many of the genes
      disrupted in both leukaemias and solid tumours. Common structural motifs are seen
      among the proteins which are brought together by translocation to produce novel
      fusion proteins. Detection of translocations in solid tumours has been made
      simpler by the introduction of molecular techniques which do not rely on
      karyotyping.

PMID- 9039728
TI  - Recent advances in the diagnosis, prognosis and classification of childhood solid
      tumours.
AB  - The diagnosis of paediatric tumours including the small round cell tumours
      (neuroblastoma, rhabdomyosarcoma and the Ewing family of tumours), brain tumours,
      germ cell tumours and anaplastic large cell lymphoma can pose particular
      diagnostic dilemmas, especially in cases with undifferentiated morphology.
      Substantial improvements have been made in the treatment and long term survival
      of paediatric patients with these tumours, however, these are based on disease
      and even stage specific treatments. Accurate diagnosis and prognosis can now be
      aided by identifying specific genotypic and phenotypic criteria using
      cytogenetics, interphase fluorescence in situ hybridisation, reverse
      transcription PCR and novel immunophenotypic markers. Some of these analyses
      should form an integral part of the management of patients with paediatric solid
      tumours.

PMID- 9039729
TI  - Lymphoblastic leukaemia and non-Hodgkin's lymphoma.
AB  - The outcome in childhood leukaemia has shown steady improvement over the last
      decade and efforts are now concentrated on the stratification of patients by risk
      factors which may avoid overtreatment of good risk patients and limit dose
      escalation strategies, including those with bone marrow transplantation, to the
      higher risk patients. In ALL, risk stratification is based on the presenting
      white cell count, sex, age and cytogenetics of the tumour cells. Even in acute
      myeloid leukaemia, the outcome with chemotherapy alone is now sufficient to limit
      elective allogeneic bone marrow transplantation to those who do not have
      cytogenetically favourable disease. In non-Hodgkins lymphoma, a dramatic
      improvement in overall survival from 50% to in excess of 80% has been achieved by
      an escalation in dose and dose intensity of chemotherapy. With this improvement,
      the prognostic influence of clinical staging has become less clear and recent
      efforts have concentrated on determining which groups of patients would be cured
      by less intensive treatment. As for ALL, there is concern about the potential
      late sequelae in these highly curable children. There remain groups of unusual
      tumour types, such as anaplastic large cell and peripheral T cell lymphoma, where
      there remains much to be learned about the pathogenesis and clinical behaviour.
      The optimum treatment strategy for these subgroups remains to be clarified.

PMID- 9039730
TI  - Acute myeloid leukaemia.
AB  - There has been considerable progress in the understanding and treatment of
      childhood acute myeloid leukaemia over the past two decades. In particular, cyto-
      and molecular genetics offer the potential for more specific diagnosis of what is
      basically a heterogeneous disease. To date treatment has been based on a steady
      increase in cytotoxic chemotherapy with or without the addition of bone marrow
      transplantation. Randomised therapeutic trials are difficult to perform in what
      is a rare disease. The best way forward is for paediatric trial groups worldwide
      to collaborate in developing common, or parallel, therapeutic protocols.

PMID- 9039731
TI  - Paediatric myelodysplasia.
AB  - Myelodysplastic syndromes (MDS) in childhood comprise a heterogeneous group of
      disorders, many of which respond poorly to intensive chemotherapy; the only
      curative treatment for these is bone marrow transplant (BMT). There are, however,
      some types of paediatric MDS with a slower, more indolent course, and it is
      important to differentiate these and tailor treatment accordingly. The prognosis
      for children with MDS who have a matched sibling BMT is improving and, as
      experience of unrelated donor BMT is gained, this treatment modality is likely to
      become available for the majority of the remainder.

PMID- 9039732
TI  - Neuroblastoma: an enigmatic disease.
AB  - Neuroblastoma is the most common extra-cranial solid tumor of childhood. It
      originates in cells of the neural crest, and so can be found anywhere along the
      paravertebral sympathetic chain or in the adrenal gland. In the last 15 years,
      new developments in the genetics and biology of neuroblastoma, have led to a
      better understanding of the natural history and prognostic features of this
      cancer. The presence of identifying biochemical markers detectable in the urine
      of patients with neuroblastoma, as well as the remarkably inferior survival of
      children diagnosed at more than 12 months of age, have led some groups to screen
      infants for neuroblastoma, in the hope of decreasing both overall mortality, as
      well as the incidence of advanced stage disease. This article reviews some
      clinical aspects of neuroblastoma, but emphasizes the genetic and biologic
      features in relation to prognosis and treatment. Finally, we discuss the
      different screening experiences for this disease, in particular from the Quebec
      Neuroblastoma Screening Project.

PMID- 9039733
TI  - Paediatric brain tumours.

PMID- 9039734
TI  - Histiocyte disorders.
AB  - Histiocyte disorders are characterised by tissue infiltration with cells of
      monocyte/macrophage lineage, with two disorders, Langerhans' cell histiocytosis
      (LCH) and haemophagocytic lymphohistiocytosis (HLH) accounting for the
      overwhelming majority of cases in childhood and, apart from monocyte variants of
      acute myeloid leukaemia, histiocytic malignancy is very rare. Although both LCH
      and HLH are considered reactive disorders, the prognosis of these conditions
      differs greatly, LCH is usually self limiting, with a mortality of 10%, but HLH
      is usually fatal, with a mortality of over 80% in the absence of bone marrow
      transplantation. Increased levels of cytokines have been demonstrated in these
      disorders, and may be responsible for many of the clinical features: it is
      unclear whether histiocytes themselves, or other immune cells, particularly T
      lymphocytes, are the abnormal cell population. Due to the rarity of histiocyte
      disorders, collaborative studies are essential to improve understanding and
      advance treatment.

PMID- 9039735
TI  - Problems and controversies in the management of childhood sarcomas.
AB  - Multidisciplinary care and advances in chemotherapy have dramatically improved
      the prognosis of paediatric sarcoma patients, but much work remains. There are
      new techniques for molecular diagnosis of Ewing's sarcomas and alveolar
      rhabdomyosarcomas, with molecular techniques of staging and subclassification
      under development. Osteosarcoma is a clinically heterogeneous disease which
      continues to resist biologic diagnosis, classification, or staging. In
      chemotherapy, the roles of ifosfamide and doxorubicin in rhabdomyosarcoma
      treatment remain unclear. While many children with metastatic or recurrent
      sarcomas undergo massive therapy with peripheral stem cell or autologous marrow
      rescue, the efficacy of these manoeuvres is debatable. Osteosarcoma appears to
      respond best to regimens containing doxorubicin and cisplatin, while the roles of
      alkylating agents, high-dose methotrexate, and carboplatin remain unclear.
      Ewing's sarcoma treatment increasingly includes surgery because of the risk of
      secondary osteosarcoma after radiation. Most osteosarcoma patients now have limb
      sparing excisions, though amputation may provide better function and cosmesis
      with less risk of complications in some patients. The role of multimodal
      treatment including chemotherapy for the miscellaneous soft tissue sarcomas
      remains uncertain.

PMID- 9039736
TI  - Future directions in the pharmacology of anti-cancer agents in children.
AB  - In the 1990s, over two-thirds of children with malignancy are expected to be long
      term survivors. This success in therapy is predominantly due to the
      chemosensitivity of childhood tumours as well as co-ordinated multi-disciplinary
      care through the use of protocols and designated children's cancer centres. In
      view of the pivotal importance of chemotherapy in childhood malignancies in the
      future therapy can be improved considerably by exploring ways to optimise
      treatment either by introducing new agents or utilising existing drugs better.

PMID- 9039737
TI  - Cancer in children: radiotherapeutic approaches.
AB  - Radiotherapy is an important treatment modality for 40-50% of children with
      cancer. There is concern about late effects, particularly the neuropsychological
      effects of CNS irradiation, and orthopaedic effects. It is important to
      administer the highest standard of radiotherapy, incorporating departmental
      quality assurance. Meticulous planning is essential to achieve local tumour
      control with the minimum of irradiation to normal tissues in order to minimise
      late effects. Current developments include better definition of tumour extent
      with MR scanning, and the use of 3D planning and conformal techniques to
      precisely match the radiotherapy target volume to the tumour. For some CNS
      tumours the role of stereotactically directed radiotherapy is being explored.
      Interactions with chemotherapy are important to improve the therapeutic ratio,
      however increased normal tissue toxicity can be problematic. Radiotherapy for
      children should be undertaken only in departments linked to specialised
      paediatric oncology centres.

PMID- 9039738
TI  - Cancer in adolescence.
AB  - Adolescence is a flexible concept reflecting specific developmental tasks but
      broadly encompassing individuals in their teens and early twenties. Comparison of
      published data from cancer registries demonstrates that the incidence of cancer
      (rate/10(6)/year) increases through the 5 year age bands 10-14 (range 100-130.1
      for males, 80-115.3 for females), 15-19 (range 154.3-220.7 for males, 127-206.7
      for females) and 20-24 (229 for males, 313 for females). Leukaemia and central
      nervous system tumours predominate in the 10-14 year group but during mid and
      late adolescence lymphomas become the main single tumour group and epithelial
      cancers become increasingly common. Arguments are presented for the formation of
      specialised adolescent cancer units based on the premise that centralisation of
      care would lead to improved treatment and survival. The physical, psychological,
      social and educational needs of adolescents are best served by the expertise of a
      single multidisciplinary team.

PMID- 9039739
TI  - The long-term survivors.
AB  - Recent research indicates that approximately 60% of children diagnosed with
      cancer in Britain are cured and as a result, about 1 in a 1000 of the general
      population will soon be survivors of childhood cancer. Unfortunately some
      elements of the therapies which are responsible for this remarkable success are
      associated with serious complications, sometimes decades after their
      administration. Therefore, a comprehensive knowledge of the risks and benefits of
      different therapies will only be obtained by monitoring the health of survivors
      indefinitely. With such therapeutic success, increasingly the composition of
      future treatment protocols will be influenced by knowledge of the risks of long
      term morbidity and mortality associated with past therapies. An awareness of the
      long term risks of complications of treatment is also important for estimating
      the future demand on the health services of this increasing proportion of the
      general population who together represent many life years of care. This chapter
      reviews what is known concerning the long term risks of complications of
      different treatments. Appropriate strategies for future clinical and
      epidemiological follow-up of the survivor population are discussed and the need
      for indefinite follow-up of the survivor population is emphasised.

PMID- 9039741
TI  - Selected ion flow tube: a technique for quantitative trace gas analysis of air
      and breath.
AB  - The selected ion flow tube (SIFT) technique for trace gas analysis of air and
      breath is based on soft chemical ionisation of the trace gases to the exclusion
      of the major air and breath gases, in fast-flowing inert carrier gas, exploiting
      the ion-molecule reactions that occur between the trace gases and the pre
      selected precursor ions (H3O+, NO+ and O2+). The physics and ion chemistry
      involved in the SIFT technique are described, as are the kinetics of the ion
      molecule reactions that are exploited to quantitatively analyse the trace gases.
      Fast on-line data-acquisition hardware and software have been developed to
      analyse the mass spectra obtained, from which partial pressures of the trace
      gases down to about 10 parts per billion can be measured. The time response of
      the instrument is 20 ms, allowing the profiles of the trace gas concentrations on
      breath to be obtained during a normal breathing cycle. Pilot results obtained
      with this SIFT technique include detection and quantification of the most
      abundant breath trace gases, analysis of cigarette smoke, detection of gases
      present on smokers' breath and accurate measurement of the partial pressures of
      NH3, NO and NO2 in air. The simultaneous analysis of several breath trace gases
      during a single exhalation is clearly demonstrated, and thus different elution
      times for isoprene and methanol along the respiratory tract are observed. This
      technique has great potential in many clinical and biological disciplines, and in
      health and safety monitoring.

PMID- 9039740
TI  - Factors affecting electrode-gel-skin interface impedance in electrical impedance
      tomography.
AB  - The magnitude, mismatch and temporal variations of the electrode-gel-skin
      interface impedance can cause problems in electrical impedance tomography (EIT)
      measurement. It is shown that at the high frequencies generally encountered in
      EIT the capacitive properties of the electrode interface, and especially those of
      the skin, are of primary importance. A wide range of techniques are reviewed that
      could possibly be used to minimise these problems. These techniques include the
      use of skin preparation, penetration enhancers, temperature and electrical
      impulses. Although several of these techniques appear very attractive, they are
      not without serious potential drawbacks. A combination of some of these
      techniques may well hold the key to success.

PMID- 9039742
TI  - Extraction and use of X-ray specific density following object-based three
      dimensional reconstruction.
AB  - Given a set of three-dimensionally reconstructed objects and the source X-ray
      images from which the reconstructions have been derived, it is shown how the
      uniform or smoothly varying X-ray specific densities (i.e. CT coefficients) of
      these objects can be derived. It is considered how that information can be used,
      inter alia, to synthesise conventional X-ray images (with unconventional
      refinements), or to compute tomographic slice images (but without textural
      information.

PMID- 9039743
TI  - Object-based three-dimensional X-ray imaging.
AB  - A form of three-dimensional X-ray imaging, called Object 3-D, is introduced,
      where the relevant subject material is represented as discrete 'objects'. The
      surface of each such object is derived accurately from the projections of its
      outline, and of its other discontinuities, in about ten conventional X-ray views,
      distributed in solid angle. This technique is suitable for many applications, and
      permits dramatic savings in radiation exposure and in data acquisition and
      manipulation. It is well matched to user-friendly interactive displays.

PMID- 9039744
TI  - Enhanced period-peak analysis of electro-encephalograms using a fast sinc
      function.
AB  - In an effort to reduce the memory space and processing time required by fast
      Fourier transforms, enhanced period-peak detection is investigated. The method is
      based on a combination of Fourier transforms and period-peak detection. The
      signal is considered as a train of truncated sinusoidal functions. Each truncated
      sinusoidal function is limited by two successive local extrema. The Fourier
      transform of the truncated sinusoidal function is a sinc function. The summation
      of these sinc functions yields an approximate frequency spectrum of the signal.

PMID- 9039745
TI  - Assessment of the humane aspects of electric lancing of whales by measurement of
      current densities in the brain and heart of dead animals.
AB  - The potential physiological effects of the electric lance are assessed, as used
      in Japanese whaling operations. Current densities are measured in the brains and
      hearts of six whales to which a controlled current of 5 A is applied by two
      electrodes inserted at various sites in the carcasses. The whales vary in size
      from 1.8 m (22 kg) to 16 m (40 t). The minimum current density in the brain
      necessary to cause depolarisation of neurones is estimated to be 10 mA cm-2 and
      to cause ventricular fibrillation is estimated to be 0.5 mA cm-2. No current
      densities exceeding 4.8 mA cm-2 are recorded in the brain. Very few recordings of
      current density from the heart are above 0.5 mA cm-2, and they occur only when
      electrodes are in optimal positions. When electrodes are placed as in whaling
      operations, no whale over 3 m in length would receive current densities in the
      heart or brain sufficient to cause permanent dysfunction. It is concluded that
      electric lancing is ineffective as a secondary method of killing whales and that
      the current densities recorded could cause pain and suffering to an already
      distressed animal.

PMID- 9039746
TI  - Ambulatory instrument for monitoring indirect beat-to-beat blood pressure in
      superficial temporal artery using volume-compensation method.
AB  - A portable instrument, based on a volume-compensation technique, is designed for
      ambulatory monitoring of indirect beat-to-beat blood pressure (BP) in the
      superficial temporal artery. The instrument consists of a small disc-type cuff
      and a portable unit carried by the subject. Several components are integrated in
      the cuff for applying counter-pressure to the artery, i.e. a reflectance-type
      photo-plethysmographic sensor for arterial volume detection, a pressure sensor
      for cuff pressure Pc measurement and a nozzle flapper-type- electro-pneumatic
      convertor for controlling Pc. The portable unit includes volume servo control
      circuitry and a microprocessor-based signal-processing and recording unit. This
      automatically performs all the necessary measurement procedures and stores into a
      memory IC element the processed systolic, mean and diastolic blood pressure data,
      together with pulse intervals on a beat-to-beat basis from the servo-controlled
      Pc (indirectly measured BP waveform). With this instrument, momentary changes in
      BP during ambulatory situations such as bicycle ergometer exercise and daily
      activities including motorway driving are successfully recorded. From the results
      of simultaneous measurement of the subject's posture changes, the effect of
      posture change on blood pressure, e.g. baroreceptor-cardiac reflex, is also
      clearly demonstrated.

PMID- 9039747
TI  - Optical aspects of a fibre-optic sensor for respiratory rate monitoring.
AB  - A new sensor for respiratory rate monitoring is described. The sensor uses an
      optical fibre that detects the evaporated humidity from the mouth and/or nose at
      each exhalation. The condensed humidity substantially alters the coupling of
      light from the optical fibre to the surrounding medium, which can be monitored by
      a photo-detector. The sensing principle is evaluated using ray-tracing simulation
      and scattering measurements.

PMID- 9039748
TI  - Comparison of shoe insole materials by neural network analysis.
AB  - The effects of two insole materials within the shoe are compared using neural
      network analysis. Seven male subjects without locomotor disorders walk on a
      treadmill at a controlled speed and cadence wearing a common shoe and no socks,
      under three conditions; these are two types of insole of the same thickness, and
      a no insole condition. Pressure-related data from under the foot, within the
      shoe, are obtained by the MICRO-EMED system during walking. A back-propagation
      neural network is trained to associate sets of pressure-related data with the
      insole conditions. Subsequently neural network analysis is performed to reveal
      the abstract rules that govern the decision-making processes within the neural
      network, based on the synergistic interactions between the measured variables.
      Data are also analysed using ANOVA. The neural network analysis finds trends in
      the way in which the trained neural network responds. The interpretation of those
      trends gives a delicate description of the dynamic behaviour of the insoles
      despite the fact that no significant differences are found using ANOVA. It is
      concluded that neural network analysis can distinguish between insole behaviour
      during use, even though these differences are not significantly different based
      on statistical tests.

PMID- 9039749
TI  - Noise of surface bio-potential electrodes based on NASICON ceramic and Ag-AgCl.
AB  - The electrochemical noise from dry NASICON-based surface electrodes and pregelled
      Ag-AgCl electrodes is evaluated in saline solutions and on the skin. The
      electrochemical noise from the electrode/electrolyte interface is found to be
      negligible (less than 1 microV peak to peak). On the skin, the noise level is
      highly dependent on the patient. At high frequencies, the skin/electrode
      interface noise is equal to 'thermal noise' and can be related to the real part
      of the skin/electrode impedance. At low frequencies (F < 100 Hz), excess noise is
      observed that varies as f-2. It is tentatively ascribed to a non-stationary
      process or noise of electrochemical origin due to the ionic nature of the skin.
      The contribution of residual EMG signal of low amplitude (5 microV peak to peak)
      is suggested for electrodes with large surface area.

PMID- 9039750
TI  - Internal work estimation in three-dimensional gait analysis.
AB  - Many studies concerning the internal work of human motion have used two
      dimensional kinematic models to estimate kinetic energy of the segments. The
      generalised co-ordinate concept has been applied here to a simultaneous and
      bilateral gait analysis. A three-dimensional kinematic model based on quaternions
      has been developed. To estimate the kinetic energy of a multi-body system, only
      two constants and two variables are needed: the segment body mass, the inertia
      tensor, the position and the orientation of the local co-ordinate system with
      respect to the inertial co-ordinate system. The variation of the kinetic energy
      is used in the calculation of the internal work for an able-bodies subject during
      the gait cycle. Both the internal work and the instantaneous energy correlation
      coefficient enable the determination of a conservative phase delimited by the
      beginning of the single support phase until the flat-foot phase, and a non
      conservative phase corresponding to the period from heel-off to contralateral
      heel-strike including the double support phase.

PMID- 9039751
TI  - Limitations of quasi-static estimation of human joint loading during locomotion.
AB  - The forces and moments at the ankle, knee and hip joints of the human lower limbs
      are divided into static and inertial components. They are calculated for various
      activities ranging from slow walking to running. The relative roles of these two
      components in the 'total' joint loads are studied, and the limitations of using a
      quasi-static analysis approach for joint load approximation are discussed. The
      results indicate that the static loads only reflect the gravitational and
      external reactions between the body and the environment, whereas the inertial
      loads provide dynamic information on each body segment involved. The effect of
      the inertial forces and moments becomes more important as the speed of locomotion
      increases; where the more proximal joints in the human lower extremity are
      concerned; and where the shear components of the force and moment are of
      interest. On the other hand, it seems that most of the joint moments in the lower
      extremity during walking and even running could reasonably be approximated by
      static components.

PMID- 9039753
TI  - Wire-core tree technique for accurate three-dimensional modelling of arterial
      trees.

PMID- 9039752
TI  - Analysis of effect of two concurrent ischaemic zones on left ventricular
      function.
AB  - Left ventricular (LV) function due to two concurrent ischaemic zones (IZs) is
      investigated using a cardiovascular system model. The model comprises a three
      compartment LV, the venous return and the arterial system. Haemodynamic responses
      of the LV to changes in the IZ size and myocardial contraction timings are
      explored. Results show that the greater the degree of asynschonisation is between
      the normal zone and the IZ, and the larger the ischaemic size, the more severe
      the LV dysfunction. Pre-load augmentation improves LV function. Model-predicted
      features are consistent with reported observations associated with myocardial
      ischaemia. The extent of the usefulness and limitations of this model is also
      discussed.

PMID- 9039754
TI  - Design and implementation of a constant-current pulsed iontophoretic stimulation
      device.

PMID- 9039755
TI  - Accuracy of 50 Hz interference subtraction from an electrocardiogram.

PMID- 9039756
TI  - Patient-controlled sputum removal during chest physiotherapy in cystic fibrosis:
      a system for use in closed-circuit assessment of energy expenditure.

PMID- 9039757
TI  - Enhanced estimation of glycated haemoglobin.

PMID- 9039759
TI  - A New Era for Microbial Ecology

PMID- 9039758
TI  - Video endoscopy testbox.

PMID- 9039760
TI  - Spatial Distribution and Coexistence of Klebsiella pneumoniae and Pseudomonas
      aeruginosa in Biofilms

PMID- 9039761
TI  - Regulation of Bacterial Growth Rates by Dissolved Organic Carbon and Temperature
      in the Equatorial Pacific Ocean

PMID- 9039762
TI  - Detection and Isolation of Methanotrophic Bacteria Possessing Soluble Methane
      Monooxygenase (sMMO) Genes Using the Polymerase Chain Reaction (PCR)

PMID- 9039763
TI  - Improved In Situ Tracking of Rhizosphere Bacteria Using Dual Staining with
      Fluorescence-Labeled Antibodies and rRNA-Targeted Oligonucleotides

PMID- 9039764
TI  - Influence of a Survival Process in a Freshwater System upon Plasmid Transfer
      Between Escherichia coli Strains

PMID- 9039765
TI  - Long-Term Adaptive Shifts in Anaerobic Community Structure in Response to a
      Sustained Cyclic Substrate Perturbation

PMID- 9039766
TI  - The Impact of Industrial Contamination on Microbial Chlorobenzoate Degradation in
      the Niagara Watershed

PMID- 9039767
TI  - Survival and Activity of Bacteria in a Deep, Aged Lake Sediment (Lake Constance)

PMID- 9039768
TI  - Microbial Community Changes During the Composting of Municipal Solid Waste

PMID- 9039769
TI  - Natural killer cell receptors and MHC class I interactions.
AB  - Natural killer cells express two distinct families of genes encoding receptors
      for polymorphic MHC class I molecules. Recent advances indicate that
      immunoreceptor tyrosine-based inhibitory motifs in the cytoplasmic domains of the
      killer cell inhibitory receptors and Ly-49 receptors recruit the SH2-containing
      protein tyrosine phosphatases, SHP-1 and SHP-2, resulting in inhibition of
      natural-killer- and T-cell-mediated cytotoxicity and cytokine secretion.

PMID- 9039770
TI  - Regulation of transcription of MHC class II genes.
AB  - Genetic and biochemical analyses have identified multiple DNA-binding and non-DNA
      binding proteins that functionally regulate MHC class II genes. These include
      RFX, X2BP, NF-Y, CIITA, OCT-2 and Bob1. One of the essential non-DNA-binding
      proteins, CIITA, appears to function as a limiting molecular switch that is
      responsible for the control of class II expression and the regulation of
      expression by interferon-gamma.

PMID- 9039771
TI  - Generation, intracellular transport and loading of peptides associated with MHC
      class I molecules.
AB  - MHC class I molecules present antigenic peptides that are mostly derived from
      endogenous cytosolic proteins. Recent studies addressing the function of the
      proteasome and its activator complexes have advanced our understanding of the
      cytosolic processing of peptides. Transporters associated with antigen processing
      (TAPs) translocate these peptides to the endoplasmic reticulum where MHC class I
      molecules, which are retained in transient complexes with chaperones and TAPs,
      await them for binding. The sequence specificity and the peptide length
      preference of TAPs roughly meet the requirements of class I molecules in a range
      of different species, suggesting evolutionary shaping of the specificity of TAPs.

PMID- 9039772
TI  - MHC class II restricted antigen presentation.
AB  - Presentation of antigenic peptides by MHC class II molecules to CD4(+) T cells
      requires many events in both the biosynthetic and endocytic pathways that must
      all occur in a controlled and coordinated fashion. In recent years the roles of
      two important chaperones, the invariant chain and the HLA-DM dimer, in promoting
      the acquisition of peptides by MHC class II molecules have largely been
      elucidated. The different compartments within the endosomal/lysosomal pathway
      that are involved in peptide loading are now being characterized. In addition to
      the specialized MHC class II compartments that exist in antigen-presenting cells,
      other intracellular compartments may also be involved in peptide loading. The
      precise mechanisms and intracellular sites of MHC class II peptide loading appear
      to dictate the nature of the T-cell epitopes presented by the antigen-presenting
      cell.

PMID- 9039773
TI  - Cytokines acting on or secreted by macrophages during intracellular infection (IL
      10, IL-12, IFN-gamma).
AB  - The three cytokines IL-12, IL-10, and IFN-gamma have important and cross
      regulatory roles in infection. In the past year, much progress has been made in
      the understanding of the cellular and molecular mechanisms involved in the
      regulation (and cross-regulation) of these three cytokines and their role in
      pathology. IL-12 is rapidly produced after infection and acts as a
      proinflammatory cytokine eliciting the production, by T cells and natural killer
      cells, of IFN-gamma which activates phagocytic cells. The production of IL-12 is
      strictly regulated by negative and positive feedback mechanisms. If IL-12 and IL
      12-induced IFN-gamma are present during early T cell expansion in response to
      antigen, Th1 cell generation is favored and the generation of Th2 cells is
      inhibited. Thus, IL-12 is also a potent immunoregulatory cytokine which promotes
      Th1 differentiation and is instrumental in the Th1-dependent resistance to
      infections by bacteria, intracellular parasites, fungi, and certain viruses.
      Viruses inducing a permanent or transient immunodepression, such as HIV and
      measles, may act, in part, by suppressing IL-12 production.

PMID- 9039774
TI  - Inter-relationship among macrophages, natural killer cells and neutrophils in
      early stages of Listeria resistance.
AB  - Reports in the past few years have shown the involvement of different cells and
      cytokines in controlling the infection with the intracellular facultative
      pathogen Listeria monocytogenes. A synergistic interaction of T-cell-independent
      and -dependent processes takes place but the nature of these interactions and of
      the relevant cells and cytokines depends on both the stage of the infection and
      the tissue that is involved.

PMID- 9039775
TI  - Innate immunity: impact on the adaptive immune response.
AB  - For many years, innate immunity has been considered as a separate entity from the
      adaptive immune response and has been regarded to be of secondary importance in
      the hierarchy of immune functions. For the past few years, however, interest in
      innate immunity has grown enormously, so that now it is studied intensively in
      many laboratories that seek to integrate these two distinct types of immune
      function. Our intent in this review is to point out the similarities and
      differences in these two types of host response to infection, and to indicate our
      present level of understanding of how these can be integrated into a more
      complete description of the immune response.

PMID- 9039776
TI  - Fc receptors.
AB  - In the past year, significant progress in the area of Fc receptor biology has
      been made in three areas: identification of the protective FcR for serum IgG half
      life (Brambell receptor), characterization of the mechanism(s) of inhibitory
      receptor Fc gamma RIIB signaling, and dissection of the in vivo roles of FcRs in
      inflammation.

PMID- 9039777
TI  - Role of natural killer cells in innate resistance to protozoan infections.
AB  - Natural killer cells are now recognized as major effectors of innate resistance
      to protozoan parasites. The principal mechanism by which they control the growth
      of these pathogens is indirect, involving cytokine production rather than
      cytolytic activity. Recent studies have identified a series of positive and
      negative signals provided by cytokines and cellular interactions which regulate
      protozoa-induced natural killer cell function.

PMID- 9039778
TI  - MHC class I and class II structures.
AB  - The basic structures of MHC class I and class II molecules are now well
      established. Over the past twelve months structural data on MHC class I molecules
      have provided details of the peptide binding groove for a number of alleles and
      have elaborated the mechanisms that allow binding of a range of peptides. Recent
      MHC class II structures have illustrated the mode of peptide binding both in
      mature complexes and in the MHC class II complex with a fragment of invariant
      chain (CLIP) during maturation.

PMID- 9039779
TI  - An innate view of gamma delta T cells.
AB  - Findings made during the past few years demonstrate that gamma delta T cells
      apparently share with macrophages a propensity to recognize nonpeptidic molecules
      of the kind most commonly associated with microorganisms and stressed cells. In
      general, recognition of these antigens by gamma delta T cells involves the
      antigen receptor but does not require antigen presenting cells to express MHC
      gene products or to have a functional antigen processing machinery. Other recent
      advances continue to support the notion that gamma delta T cells can perform
      specialized functions related to the repair of tissue damage.

PMID- 9039780
TI  - Role of murine NK cells and their receptors in hybrid resistance.
AB  - Hybrid resistance refers to the rejection of parental strain bone marrow cells by
      natural killer cells of mice that are F1 hybrids derived from two inbred parental
      strains. This pattern of rejection is not seen in solid organ transplants.
      Progress in understanding this exception to the laws of transplantation genetics
      has occurred with the recent discovery of negative signaling receptors for MHC
      class I molecules. In the last year the discovery of natural killer cell subsets
      with non-overlapping inhibitory receptors for parental class I molecules has
      provided an explanation for hybrid resistance. In some instances, however,
      positive rather than negative signaling seems to be the basis for rejection of
      allogeneic as well as parental marrow cell grafts.

PMID- 9039781
TI  - Biophysical and structural studies of TCRs and ligands: implications for T cell
      signaling.
AB  - The availability of soluble alphabeta TCRs and the individual chains has now made
      it possible to carry out structural studies of these molecules and analyze their
      molecular interactions with peptide-MHC ligands. Recent X-ray crystallographic
      structures of TCR alpha and beta chains have finally established their structural
      similarity with the lg molecules. Kinetic measurements of the interaction between
      TCRs and their ligands have provided strong evidence in favour of an
      affinity/avidity model for T cell activation in the periphery as well as during
      development in the thymus.

PMID- 9039782
TI  - Activation and function of natural killer cell responses during viral infections.
AB  - Although the role of natural killer (NK) cells in defense against certain viral
      infections has been appreciated for a number of years, characterization of the
      virus-induced endogenous mechanisms regulating NK cell responses and functions
      has been limited to interferon (IFN)-alpha/beta-mediated activation of NK cell
      cytotoxicity. Studies of experimental infections have demonstrated that virus
      induced NK cells undergo blastogenesis and can be activated to produce IFN-gamma.
      Recent work has shown that some, but not all, viral infections induce IL-12, the
      expression of which results in NK cell IFN-gamma production, and that NK cell IFN
      gamma production contributes to an antiviral state. IL-12 expression can be
      regulated by IFN-alpha/beta, and endogenous IFN-alpha/beta is responsible for the
      lack of IL-12 during viral infections that fail to elicit detectable production
      of this factor. Once T cell responses are activated, additional mechanisms are in
      place to turn off NK cell functions. These studies demonstrate that viral
      infections elicit unique mechanisms for regulating NK cell responses, and suggest
      that the host requires tight control of NK cells under these conditions.

PMID- 9039783
TI  - Innate pathways that control acquired immunity.

PMID- 9039784
TI  - Origin, maturation and antigen presenting function of dendritic cells.
AB  - Dendritic cells are cells specialized for antigen capture, migration and T cell
      stimulation. Recent advances have been made in understanding their origin, their
      heterogeneity, the mechanism of antigen uptake, and the signals that induce their
      migration and maturation into immunostimulatory antigen-presenting cells.
      Dendritic cells represent the natural adjuvants for T cell responses and their
      therapeutic exploitation in the near future is foreseen.

PMID- 9039785
TI  - Complement and the immune response.
AB  - This past year has seen a major advance in our understanding of how the
      complement system enhances the adaptive immune response. The use of in vivo
      models has revealed that direct coupling of C3d to antigen is sufficient to
      dramatically reduce the amount of antigen required for a secondary response. At
      least one important requirement for the enhancing effect was determined to be
      expression of the CD21 (C3d receptor) on B cells.

PMID- 9039787
TI  - Antigen recognition.

PMID- 9039786
TI  - Specificity in V(D)J recombination: new lessons from biochemistry and genetics.
AB  - Recent in vitro work on V(D)J recombination has helped to clarify its mechanism.
      The first stage of the reaction, which can be reproduced with the purified RAG1
      and RAG2 proteins, is a site-specific cleavage that generates the same broken DNA
      species found in vivo. The cleavage reaction is closely related to known types of
      transpositional recombination, such as that of HIV integrase. All the site
      specificity of V(D)J recombination, including the 12/23 rule, is determined by
      the RAG proteins. The later steps largely overlap with the repair of radiation
      induced DNA double-strand breaks, as indicated by the identity of several newly
      characterized factors involved in repair. These developments open the way for a
      thorough biochemical study of V(D)J recombination.

PMID- 9039788
TI  - The Eph family in retinal axon guidance.
AB  - The continued functional characterization of Eph-related receptors and ligands
      has provided further information toward an understanding of the mechanisms
      controlling the retinotectal projection. Recent in vivo analyses have
      strengthened the idea that Engrailed defines the positional identity of the
      tectum along the anteroposterior axis, possibly by regulating the expression of
      Eph family members.

PMID- 9039789
TI  - Neural induction in Xenopus laevis: evidence for the default model.
AB  - At gastrulation, vertebrate ectoderm is competent to differentiate into either
      neural tissue or epidermis. Several soluble factors that can neuralize ectoderm
      in explant cultures have been isolated. Alternatively, neuralization can be
      achieved by dissociating the cells of the blastula ectoderm. These various
      treatments appear to neuralize by blocking or diluting out the action of an
      epidermal-inducing factor. Recent results demonstrate that bone morphogenetic
      protein 4 (BMP-4), a member of the transforming growth factor beta (TGF-beta)
      ligand superfamily, is a potent neural inhibitor and epidermal inducer and may
      represent the endogenous epidermal-inducing factor.

PMID- 9039790
TI  - Cell fate determination in Drosophila.
AB  - A major issue in development is to understand how local heterogeneities are
      interpreted to determine specific cell fates. The sense organs of Drosophila
      provide an accessible system for addressing this issue. Most sense organs
      comprise four types of cells, and their differentiation is the outcome of a
      complex developmental programme comprising several steps. Recent results
      illuminate, for several of these steps, the nature of the local heterogeneities
      and the mechanism used to interpret them in terms of cell fate decisions.

PMID- 9039791
TI  - Tyrosine phosphorylation and axon guidance: of mice and flies.
AB  - Recent genetic evidence suggests that tyrosine kinases and tyrosine phosphatases
      can control the guidance of specific growth cones. Within a family of related
      phosphatases or kinases, individual members can have partially redundant
      functions. Receptor phosphatases can work together at one guidance choice point,
      but in opposition at another. The specific combination of kinases and
      phosphatases active in a growth cone may be an important determinant of pathway
      choice. One mechanism by which these proteins could control guidance decisions is
      through regulation of adhesion between growth cones and axons.

PMID- 9039792
TI  - The genetics of visual system development in Drosophila: specification,
      connectivity and asymmetry.
AB  - Encoding visual information requires a complex neuronal network. Recently, genes
      regulating early tissue specification, the growth of retinal target structures,
      the connectivity of photoreceptor axons, and mirror-image retinal symmetry in
      Drosophila have been identified. The insights gained from studying visual system
      development in flies promise to inform our understanding of similar processes in
      vertebrates.

PMID- 9039793
TI  - Hedgehog signaling in Drosophila eye and limb development - conserved machinery,
      divergent roles?
AB  - The secreted signaling molecule Hedgehog plays a key role in patterning
      Drosophila eyes and limbs. Recently, the transmembrane proteins Patched and
      Smoothened and the Gli protein Cubitus interruptus have been identified as
      essential components in Hedgehog signal transduction. Progress has also been made
      in understanding the function of Decapentaplegic (Dpp) in mediating the Hedgehog
      signal. Although playing only a minor role in the eye, Dpp governs, at long
      range, the expression of essential genes such as optomotor blind and spalt in the
      wing.

PMID- 9039794
TI  - Neuregulins and neuregulin receptors in neural development.
AB  - The neuregulins are a family of closely related proteins that play important
      roles in neural and cardiac development, as well as in mammary carcinogenesis.
      The pleiotropic activities of these molecules are transduced by a set of receptor
      protein tyrosine kinases that exhibit structural similarity to the receptor for
      epidermal growth factor. Recent results have demonstrated essential roles for the
      neuregulins and their receptors in regulating cell number, determining cell fate,
      and establishing pattern in the developing central and peripheral nervous
      systems.

PMID- 9039795
TI  - Genes and lineages in the formation of the enteric nervous system.
AB  - The enteric nervous system is large, complex, and independent of the CNS. Its
      neural-crest-derived precursors migrate along defined pathways to colonize the
      bowel. Recent studies of the sequential actions of essential growth and
      transcription factors have revealed that enteric neuronal development involves a
      complex interaction of lineage-determined and microenvironmental elements.

PMID- 9039796
TI  - Genetic analysis of postsynaptic differentiation at the vertebrate neuromuscular
      junction.
AB  - As neuromuscular junctions form in vertebrate skeletal muscle, nicotinic
      acetylcholine receptors (AChRs) become concentrated in the postsynaptic membrane.
      The nerve directs this redistribution, using multiple signals to regulate AChRs
      at both transcriptional and post-translational levels. Recent studies in vitro
      have led to the identification of candidate nerve-derived signaling molecules
      (such as agrin, ARIA/neuregulin, and calcitonin gene-related peptide) and
      components of their intramuscular signaling pathways (including dystroglycan,
      MuSK, erbB kinases, utrophin, and rapsyn). Studies of knock-out mice are now
      making it possible to test which signals and pathways are responsible for
      postsynaptic differentiation in vivo.

PMID- 9039797
TI  - Regionalization in the mammalian telencephalon.
AB  - Regionalization in the telencephalon results in the formation of functionally and
      anatomically distinct territories. Cell fate analysis and gene expression studies
      suggest these subdivisions arise relatively late in development compared with the
      spinal cord or hindbrain. The mechanisms underlying the commitment of
      telencephalic cells to specific regional identities have been examined through
      recent transplantation experiments.

PMID- 9039798
TI  - Rho family GTP-binding proteins in growth cone signalling.
AB  - Rho family GTP-binding proteins regulate various aspects of the actin
      cytoskeleton in a wide variety of organisms. Recent evidence suggests that they
      may also be important components of the signalling pathways that link the
      reception of extracellular cues to the regulation of the cytoskeleton in neuronal
      growth cones.

PMID- 9039799
TI  - Basic helix-loop-helix genes in neural development.
AB  - Several major advances in the understanding of the regulation of vertebrate
      neurogenesis by members of the basic helix-loop-helix (bHLH) protein family have
      been made in the past year. Specifically, a number of bHLH genes have been cloned
      and shown to convert non-neuronal fate to neuronal fate when expressed
      ectopically. In particular, studies on NeuroD and Neurogenin suggest a regulatory
      pathway, providing powerful molecular tools to study vertebrate neurogenesis.

PMID- 9039800
TI  - Asymmetric division and polarity of neuroepithelial cells.
AB  - Neuroepithelial cells, the progenitors to the CNS neurons and glia, undergo both
      symmetric and asymmetric divisions. Symmetric divisions underlie the
      proliferation of neuroepithelial cells that predominates early in CNS
      development. Asymmetric divisions are thought to generate the cell types derived
      from neuroepithelial cells, such as neurons. Insight into the mechanism of
      asymmetric division of neuroepithelial cells has come from two lines of research,
      the study of their epithelial polarity and the analysis of the expression of
      vertebrate homologues of proteins known to be involved in cell fate determination
      in Drosophila.

PMID- 9039801
TI  - Genetics of neural development in zebrafish.
AB  - Large-scale mutant screens in zebrafish have led to the identification of more
      than 50 genes affecting various aspects of neural development and function,
      including neural induction, anteroposterior and dorsoventral regionalization,
      axon pathfinding, neuronal differentiation and survival, and behavior. Phenotypic
      analysis of mutants for some of these genes has already uncovered important
      genetic and cellular interactions during development. Ongoing molecular analyses
      promise to further elucidate the mechanisms underlying neural development in
      vertebrates.

PMID- 9039802
TI  - Neurotrophin switching: where does it stand?
AB  - In vitro and in vivo studies suggest that certain populations of neurons switch
      their survival requirements from one neurotrophin to another during an early
      stage in their development. Although there is good evidence for neurotrophin
      switching in sensory neurons, the evidence for switching in sympathetic neurons
      has become more controversial, as has the identity of the factors that regulate
      their responsiveness to particular neurotrophins.

PMID- 9039803
TI  - Genes involved in cerebellar cell specification and differentiation.
AB  - The conservation of transcriptional regulatory mechanisms across species,
      combined with the restricted expression of these molecules in time and space
      within the embryo, has offered new insights into CNS cell specification. Studies
      examining transcriptional control in the generation of specific cell classes
      within the cerebellar cortex have been particularly elucidative.

PMID- 9039804
TI  - Development. The end of the beginning?

PMID- 9039805
TI  - Web alert. Development.

PMID- 9039806
TI  - Oesophageal cancer: hope for the future?

PMID- 9039807
TI  - The roles of the human major histocompatibility complex and human papillomavirus
      infection in cervical intraepithelial neoplasia and cervical cancer.

PMID- 9039808
TI  - Molecular genetics of colorectal cancer (part 1).

PMID- 9039809
TI  - A short fractionation radiotherapy treatment for poor prognosis patients with
      high grade glioma.
AB  - Thirty-two patients prospectively identified as having poor prognosis high grade
      glioma, with a MRC prognostic score >25, were treated with a short palliative
      course of radiotherapy. A total dose of 36 Gy in 12 fractions was given to the
      tumour, including oedema and a 2 cm margin, using parallel pair fields prescribed
      to the midplane with MV photons. Twenty-eight patients completed treatment as
      planned, while four failed to complete treatment because of clinical
      deterioration or death. The median survival for the whole group was 16 weeks,
      with seven patients surviving for more than 6 months. Approximately two-thirds of
      the surviving patients remained at home after the completion of treatment. A
      matched case-control comparison with data from patients in previous MRC studies
      who had received a 6-week course of treatment shows that, for this group of
      patients, survival is similar (hazard ratio 1.0; 95% confidence interval (CI)
      0.57-1.74). The 95% CI for the difference in median survival time excludes a
      reduction of more than 7 weeks with the 36 Gy course. This shortened radiotherapy
      regimen may therefore be satisfactory for most poor prognosis patients. However,
      patients with performance status 3 gained little benefit from treatment, and it
      is suggested that this group should have a trial period of assessment at home
      prior to a decision on treatment.

PMID- 9039810
TI  - When and how to discharge cancer survivors in long term remission from follow-up:
      the effectiveness of a contract.
AB  - This study aimed to examine a formal planned system of discharge from the
      oncology clinic of a district general hospital for long term cancer survivors.
      The mainstay of this system lay in a written contract between the doctor and the
      patient, which accepted continuing responsibility after discharge. During a 6
      month period, 65 consecutive cancer patients who were in long-standing remission
      were interviewed and offered discharge according to the terms of the contract. Of
      these, 41 accepted and signed the contract. At 4 months postdischarge, patients
      were visited in their homes and their views sought on the effectiveness of the
      contract in terms of reassurance and their experience of being discharged after
      so many years of follow-up care. At a median interval of 13 months (range 6-18),
      six patients have returned to the clinic. The remaining 35 patients appeared to
      be successfully rehabilitated to primary care. Anxiety and fear that recurrence
      would not be detected were the major factors associated with refusal to accept
      the discharge contract.

PMID- 9039811
TI  - Pyridinium crosslinks in the monitoring of patients with bone metastases from
      carcinoma of the breast.
AB  - Assessing the response of bone metastases to systemic therapy remains a difficult
      clinical problem. The currently available markers of bone disease are limited by
      the length of time before the changes that accompany regression or progression
      become evident. The pyridinium crosslinks, pyridinoline (Pyr) and
      deoxypyridinoline (dPyr), are a recently described group of compounds formed by
      collagen breakdown. Elevated urinary crosslinks were demonstrated in patients
      with bone metastases when compared with controls (P<0.0001). Improvements in the
      sensitivity of the high performance liquid chromatography technique have enabled
      us to measure these compounds in serum for the first time; Pyr and dPyr were also
      significantly elevated when compared with controls (P<0.001). We found
      significant correlations between Pyr and dPyr in serum (p = 0.88; P<0.0001) as
      well as in urine (p = 0.94; P<0.0001). In addition, a significant relationship
      existed between serum Pyr and the percentage of bone involved (p = 0.78;
      P<0.0001). Here we describe or preliminary results using this new assay and
      consider the role of these markers in the clinical assessment of metastatic bone
      disease from breast cancer.

PMID- 9039812
TI  - The importance of three-dimensional brachytherapy treatment planning for
      nasopharyngeal carcinoma.
AB  - High dose rate (HDR) intracavitary brachytherapy is now more frequently
      incorporated into treatment programmes for patients with persistent and recurrent
      nasopharyngeal carcinoma (NPC). However, many centres still employ two
      dimensional (2-D) image reconstruction for applicators with a three-dimensional
      (3-D) orientation. In this study, we introduced the use of a mobile modified
      Nucletron reconstruction box inside the brachytherapy suite for image
      reconstruction and quality assurance. Three-dimensional reconstruction of the
      applicators' configurations proved possible and the dose distributions generated
      by the 2-D and 3-D image reconstructions could be compared. Thirty-one
      applications were included in this part of the analysis. The results showed that,
      based on the 2-D planning method, the reference doses were under-prescribed by 1%
      10% in all except one patient, whose dose was over-prescribed by 3%. The
      evaluated doses to the floor of the sphenoid, which was shown to be significant
      for subsequent local control, was shown to be underestimated by up to 19% or
      overestimated by 18%, with an average of 5.9% dose underestimation. With this
      system, the reliability of the anchoring techniques was verified by posttherapy
      radiographs. Any catheter displacement of more than 1 mm was counted as a
      failure. Nine of the 43 verified applications were classified as failures,
      although six of nine catheter displacements measured < or = 2.5 mm. We recommend
      the routine use of a modified reconstruction box for 3-D image reconstruction for
      dose calculation and prescription in the treatment of NPC with HDR intracavitary
      brachytherapy. Quality assurance programmes should be included as an integral
      part of any HDR treatment; their importance cannot be overemphasized.

PMID- 9039813
TI  - Dosimetric considerations in the treatment of inoperable endometrial carcinoma by
      a high dose rate afterloading packing technique.
AB  - A series of 23 patients with early adenocarcinoma of the endometrium who
      underwent a total of 37 modified Heyman packings treated on a high dose rate
      Microselectron has been reviewed. Using computed tomography (CT), the uterine
      wall thickness was measured retrospectively and doses calculated at a number of
      points on the uterine serosa and related normal tissues. The mean and maximum
      fundal serosal doses were found to be highest posteriorly and the sigmoid colon
      was adjacent to the posterior surface of the uterus in all instances. By
      superimposing the isodose distribution on CT sections of the uterus, it is now
      possible to prescribe to a serosal dose, or, in patients too heavy for the CT
      scanner, a dose can be prescribed to a point S, which is a reasonable
      approximation to the serosal position. Since the initial study, a further ten
      patients have been treated by the same method and, where relevant, data from all
      33 patients have been used.

PMID- 9039814
TI  - Clinical efficacy of perceived 'CNS friendly' chemoradiotherapy for primary
      intracranial germ cell tumours.
AB  - The optimal treatment of intracranial germ cell tumours (IGCT) is controversial.
      The late sequelae of craniospinal radiotherapy and the high response rate to
      chemotherapy have led to new treatment strategies. The morbidity of combined
      modality therapy has tempered enthusiasm for aggressive chemoradiotherapy. In
      1992, we described new lower morbidity chemotherapy and radiotherapy methods to
      be used in conjunction for IGCT treatment, employing three drugs (vincristine,
      carboplatin, etoposide) and a differential daily dose neuraxis radiotherapy
      technique (to replace a shrinking field technique). The chemoradiotherapy had the
      potential for a graded intensity reduction when high cure rates were maintained.
      Of 13 IGCT patients treated on this protocol, 8/8 germinomatous GCT and 3/5 non
      germinomatous GCTs are in continuing remission. These observations have
      implications for other CNS tumour treatments in (young) patients, in whom late
      CNS toxicity (particularly neuropsychological) is a problem.

PMID- 9039815
TI  - Antisense therapy: therapeutic magic bullet or theoretical dream?

PMID- 9039816
TI  - Prognostic and therapeutic implications of tumour angiogenesis.

PMID- 9039817
TI  - Oral pilocarpine improves radiotherapy-induced dry eyes.
AB  - We report a patient with angiosarcoma of the scalp, who was treated with
      radiotherapy that included both orbits. Following treatment, he developed dry
      eyes, which improved with oral pilocarpine. Although this drug is used to
      stimulate salivary flow in patients with radiotherapy-induced xerostomia, it has
      not been reported before as a treatment for dry eyes following radiotherapy.

PMID- 9039818
TI  - E. L. Robert Stokstad (1913-1995).

PMID- 9039819
TI  - Fetal exposure to low protein maternal diet alters the susceptibility of young
      adult rats to sulfur dioxide-induced lung injury.
AB  - The maternal diet is an important determinant of glutathione-related metabolism
      in rats. Glutathione (GSH) may play a major role in the detoxification of sulfur
      dioxide (SO2) within the lungs. The effects of fetal exposure to a low protein
      maternal diet upon later susceptibility to pulmonary injury induced by chronic
      SO2 exposure were evaluated in young adult rats. Pregnant rats were fed purified
      diets containing 180 g casein/kg (control diet) or 120, 90 or 60 g casein/kg
      (experimental diets). After parturition, all dams were fed a standard non
      purified diet (189 g protein/kg diet). The pups thus differed only in terms of
      protein nutrition during gestation. At seven wk of age the male pups were housed
      in either room air or 286 microg SO2/m3 for 5 h/d during a 28-d period. At the
      end of the final SO2 treatment period, the rats exposed to 90 or 60 g casein/kg
      diets in utero exhibited significantly greater pulmonary injury, as assessed by
      bronchoalveolar lavage, than did those exposed to control diet in utero.
      Significant maternal diet-induced differences in activities of enzymes of the
      gamma-glutamyl cycle were noted in the lungs and livers of rats which had not
      undergone SO2 treatment. Furthermore, the response of these enzyme activities to
      SO2 treatment was determined by prior exposure to the maternal diet. SO2-treated
      rats exposed to control diet (180 g casein/kg) and low protein diet (60 g
      casein/kg), but not those exposed to 120 or 90 g casein/kg diets, tended to
      augment the activities, relative to rats not treated with SO2, of enzymes which
      maintain tissue GSH status either through synthesis or recycling. Differences in
      susceptibility to SO2-induced tissue injury may be related to programming of GSH
      metabolism by the maternal diet. Alternatively, impaired immune and acute phase
      responses to an inflammatory insult may account for a failure to resolve initial
      SO2-induced injury in rats exposed to low protein maternal diets.

PMID- 9039820
TI  - Food restriction reduces aflatoxin B1 (AFB1)-DNA adduct formation, AFB1
      glutathione conjugation, and DNA damage in AFB1-treated male F344 rats and B6C3F1
      mice.
AB  - The objective of this study was to examine effects of food restriction (FR) on
      the metabolic activation of aflatoxin B1 (AFB1) in rats and mice, which are AFB1
      sensitive and -resistant rodent species, respectively. Forty percent FR [60% of
      ad libitum (AL) food consumption] reduced the metabolic activation of AFB1 in
      both rats and mice, causing formation of hepatic AFB1-DNA adducts to be 43% and
      31% lower, respectively. The AFB1-DNA adduct 8,9-dihydro-8-(N7-guanyl)-9
      hydroxyaflatoxin B1 (AFB1-N7-Gua) was predominantly formed in rat liver DNA; the
      formation of the ring-open analogue of AFB1-N7-Gua, AFB1-formamidopyrimidine
      (AFB1-FAP), was predominantly found in mouse liver DNA. In contrast to the in
      vivo results, the in vitro AFB1-DNA adduct formation mediated by the microsomes
      of liver, kidney or lung from FR-mice was greater than the formation of AFB1-DNA
      adducts mediated by the tissue microsomes from the AL-mice. Food restriction
      induced hepatic glutathione S-transferase (GST) activity, as measured by the
      formation of AFB1-glutathione conjugates (AFB1-SG), in both rats and mice; AFB1
      SG was also formed in mouse kidney. Food restriction-induced GST activity assayed
      in an in vitro system, using [3H]AFB1-8,9-epoxide and glutathione (GSH) as
      substrates, was also found when mouse kidney and lung cytosolic fractions were
      used. Food restriction inhibited the AFB1-induced DNA double strand breaks in
      mouse kidney. The reduction of levels of AFB1-DNA adduct formation in mouse
      kidney was comparable to the degree of AFB1-induced DNA strand breakages. The
      results of this study indicate that the metabolic activation of AFB1 can be
      modulated by FR through the alteration of the formation of AFB1-DNA adducts and
      AFB1-SG conjugation. However, species and tissue specificities exist regarding
      the metabolic activation of AFB1.

PMID- 9039821
TI  - Lecithin:retinol acyltransferase and retinyl ester hydrolase activities are
      differentially regulated by retinoids and have distinct distributions between
      hepatocyte and nonparenchymal cell fractions of rat liver.
AB  - The cellular distribution of enzymes that esterify retinol and hydrolyze retinyl
      esters (RE) was studied in liver of vitamin A-sufficient, -deficient, and
      deficient rats treated with retinoic acid or N-(4-hydroxyphenyl)-retinamide.
      Livers were perfused and cell fractions enriched in hepatocytes, and
      nonparenchymal cells were obtained for assays of RE and enzyme activity. The
      specific activity of lecithin:retinol acyltransferase (LRAT) was approximately 10
      fold greater in the nonparenchymal cell than the hepatocyte fraction from both
      vitamin A-sufficient and retinoid-treated rats. Total RE mass, newly synthesized
      [3H]RE and LRAT activity were positively correlated in liver and isolated cells
      of both normal (P < 0.0001) and retinoid-treated rats (P < 0.0002). In
      nonparenchymal cells, these three constituents were nearly equally enriched as
      evaluated by their relative specific activity values (RSA, defined as the
      percentage of recovered activity divided by the percentage of recovered protein),
      which were each significantly greater than 1.0, with values of 4.3 for total RE
      mass (P < 0.05), 3.6 for newly synthesized [3H]RE (P < 0.01) and 3.8 for LRAT
      activity (P < 0.01). In contrast, the specific activities of neutral and acid
      bile salt-independent retinyl ester hydrolases (REH) did not vary with vitamin A
      status, and their RSA values were close to 1.0 in both hepatocytes and
      nonparenchymal cells. These data show that LRAT and REH are differentially
      regulated by retinoids and that these enzymes also differ in their spacial
      distribution between liver parenchymal and nonparenchymal cells.

PMID- 9039822
TI  - Dietary fat and protein intake differ in modulation of prostate tumor growth,
      prolactin secretion and metabolism, and prostate gland prolactin binding capacity
      in rats.
AB  - The combined effects of dietary fat and protein concentration on prostate tumor
      growth and endocrine homeostasis were evaluated in male rats. A 2 x 2 factorial
      experiment examined the effects of protein (5 and 20% of energy as casein) and
      fat (10 and 40% of energy as corn oil) on the growth of the Dunning R3327-H
      transplantable prostate adenocarcinoma in Copenhagen x Fisher F1 rats. Rats fed
      protein-restricted diets for 20 wk exhibited lower energy intakes, final body
      weights and tumor growth rates. Weanling male Sprague-Dawley rats fed protein
      restricted diets for 4 wk had serum concentrations of prolactin, growth hormone
      and testosterone which were 68, 17 and 85% of controls, respectively. After 16 wk
      of feeding, there were no effects of dietary protein on serum hormone
      concentrations despite reduced energy intake and body weight. The metabolic
      clearance rate of serum prolactin was lower in rats fed the low protein diets for
      4 or 16 wk; however, no differences were noted when adjusted for body weight. In
      vivo studies employing intravenously injected 125I-labeled prolactin revealed
      slight alterations in the metabolism of circulating prolactin monomer or binding
      to serum proteins in protein-restricted rats. The maximal binding capacity of
      prolactin receptors on the prostate membrane fraction was 42% lower in rats fed
      diets restricted in protein despite normal serum hormone concentrations at 16 wk.
      Dietary fat had no effect on tumor growth or prolactin homeostasis although a
      slightly greater serum testosterone was noted in rats fed high fat diets. In
      contrast, restriction of dietary protein caused significant changes in energy
      intake, serum hormone concentrations, prolactin metabolism, prostatic prolactin
      binding capacity and prostate tumor growth rates. These studies support the
      hypothesis that dietary protein and energy intake, particularly during periods of
      rapid growth and development, may alter prostate biology and modulate the risk of
      future prostate cancer progression.

PMID- 9039823
TI  - Dietary iron intake modulates the activity of iron regulatory proteins and the
      abundance of ferritin and mitochondrial aconitase in rat liver.
AB  - Iron regulatory protein 1 (IRP1) and IRP2 are cytoplasmic RNA binding proteins
      that coordinate cellular iron homeostasis in mammals. We investigated the effect
      of dietary iron intake on rat liver IRP activity in relation to the abundance of
      two targets of IRP action, ferritin and mitochondrial aconitase (m-aconitase).
      Rats were fed diets containing 2, 11, 20, 37 (control), 72 or 107 mg iron/kg diet
      for 3 wk. RNA binding activity of IRP1 and IRP2 was enhanced one- to twofold in
      rats fed 11 or 2 mg iron/kg diet compared with control rats. IRP RNA binding
      activity was inversely correlated to blood hemoglobin levels (r = -0.787; P <
      0.0001). Compared with control rats, liver ferritin levels were depressed in rats
      fed 20 mg iron/kg diet and were undetectable in rats ingesting diets with 11 or 2
      mg iron/kg diet. Ferritin concentrations were biphasically related to IRP RNA
      binding activity with the regulation of IRP occurring before the onset of
      ferritin accumulation. Iron deficiency caused up to a 50% decline in m-aconitase
      abundance. IRP RNA binding activity and m-aconitase abundance were inversely
      correlated (r = -0.751; P < 0.0001). Our results indicate that (1) liver IRP
      activity is responsive to a range of dietary iron levels, (2) there appears to be
      a differential effect of IRPs on ferritin and m-aconitase abundance, and (3)
      activation of IRPs may contribute to the alterations in energy metabolism in iron
      deficiency through an impairment of m-aconitase synthesis.

PMID- 9039824
TI  - Inhibiting delta9-desaturase activity impairs triacylglycerol secretion in
      cultured chicken hepatocytes.
AB  - The relationship between endogenous oleic acid produced by hepatic delta9
      desaturase and the secretion of VLDL-triglycerides was investigated in a primary
      culture of chicken hepatocytes. When the fatty acid compositions of the secreted
      and intracellular triglycerides (TG) (or triacylglycerols) were compared, an
      imbalance between monoenes and saturated fatty acids was observed, with the
      secreted TG being significantly more unsaturated than the intracellular TG. The
      addition of a mixture of cyclopropenic fatty acids (specific inhibitors of fatty
      acid desaturation) to the culture medium of cells 24 h before measurement of
      their delta9-desaturase activity and TG secretion rate caused a significant
      impairment of both desaturase activity and TG secretion, without affecting total
      TG synthesis. However, the addition of oleic acid to the culture medium of cells
      treated with cyclopropenic fatty acids restored the TG secretion rate. Palmitic
      acid did not restore the TG secretion rate and linoleic acid partly restored the
      TG secretion rate. Finally, even in the presence of oleic acid in the culture
      medium of secreting cells, those which had been treated with cyclopropenic fatty
      acids had a significantly lower TG secretion rate than nontreated cells. Taken
      together, these results show that TG secretion is highly dependent on the delta9
      desaturase activity and suggest that oversecretion of VLDL-TG in chickens and
      subsequent fattening could originate in a high hepatic delta9-desaturation of
      saturated fatty acids.

PMID- 9039825
TI  - Copper deficiency reduces interleukin-2 (IL-2) production and IL-2 mRNA in human
      T-lymphocytes.
AB  - Although dietary copper (Cu) deficiency has been associated with decreased
      production of interleukin-2 (IL-2) by activated splenic mononuclear cells in
      rodent models, the basis for this relationship and its relevance for humans
      remain unknown. To address these matters, we have developed an in vitro model of
      cellular copper deficiency by treating Jurkat, a human T-lymphocyte cell line,
      with low concentrations of 2,3,2-tetraamine (2,3,2-tet), a high affinity copper
      chelator. Exposure to 5-20 micromol/L 2,3,2-tet for 35 h decreased cell copper
      and the activity of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) by 30-40% and IL-2
      production by 60-70% in cultures activated with phytohemagglutinin and phorbol
      myristate acetate. Similarly, IL-2 mRNA levels were 40-70% lower in chelator
      treated cells than in untreated cells at 3-12 h after activation. In contrast,
      chelator treatment had no significant effect on cell viability, growth, protein
      synthesis or mitochondrial activity. The presence of a slight molar excess of
      copper, but not zinc or iron, during exposure to 2,3,2-tet prevented the chelator
      induced decrease in Cu,Zn-SOD activity and the reductions in IL-2 mRNA and
      bioactivity. Moreover, binding of diferric transferrin (Tf) and cellular uptake
      of Tf-59Fe by Jurkat cells were not increased by 2,3,2-tet, indicating that
      chelator-treated cells were not iron deficient. Finally, incubation of human
      peripheral blood mononuclear cells (PBMC) with 2,3,2-tet decreased mitogen
      induced IL-2 production by 50% compared with untreated controls. These data
      indicate that a decline in copper status decreases IL-2 production by activated
      human T-cells due to reduced synthesis and/or stability of IL-2 mRNA.

PMID- 9039826
TI  - Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and
      the hypothalamic/pituitary axis in rats.
AB  - These studies were undertaken to assess the estrogenic and antiestrogenic effects
      of dietary genistein. To determine estrogenic effects, genistein was mixed into a
      modified AIN-76 or AIN-93G semipurified diet at 0 (negative control), 150, 375 or
      750 microg/g and 17, beta-estradiol at 1.0 microg/g and fed to ovariectomized 70
      d-old Sprague-Dawley rats. Estrogenic potency was determined by analyzing uterine
      weight, mammary gland development, plasma prolactin and expression of uterine c
      fos. Dietary genistein (375 and 750 microg/g) increased uterine wet and dry
      weights (P < 0.05). Mammary gland regression following ovariectomy was
      significantly inhibited by dietary genistein at 750 microg/g (P < 0.05). Plasma
      prolactin was significantly greater in ovariectomized rats fed genistein (750
      microg/g) compared with comparable rats not receiving genistein. The relative
      binding affinity of genistein to the estrogen receptor (ER) was 0.01 that of
      estradiol. Genistein (750 microg/g) induced the uterine expression of c-fos. To
      evaluate potential antiestrogenic effects, genistein and estradiol were mixed
      into the modified AIN diets at the doses noted above and fed to ovariectomized
      rats. Dietary genistein (375 or 750 microg/g) did not inhibit the effects of
      estradiol on uterine weight, mammary gland development or plasma prolactin. Serum
      concentration of total genistein (conjugated plus free) in rats fed 750 microg/g
      was 2.2 micromol/L and free genistein was 0.4 micromol/L. Administration of
      dietary genistein at 750 microg/g can exert estrogenic effects in the uterus,
      mammary gland and hypothalamic/pituitary axis. Dietary genistein (750 microg/g)
      did not antagonize the action of estradiol in estradiol-supplemented
      ovariectomized rats or in intact rats.

PMID- 9039827
TI  - Differences in tryptophan binding to hepatic nuclei of NZBWF1 and Swiss mice:
      insight into mechanism of tryptophan's effects.
AB  - We have observed that in NZBWF1 mice the affinity for L-tryptophan binding to
      hepatic nuclei in vitro is markedly less than that of Swiss mice. In vitro
      binding of [3H]tryptophan to hepatic nuclei from both strains was determined
      without and with unlabeled L-tryptophan (10(-4) mol/L). The relative specific
      binding of L-tryptophan to hepatic nuclei in vitro was 60.9 +/- 4.4% for Swiss
      mice and 35.8 +/- 5.4% (P < 0.01) in NZBWF1 mice. The total specific binding
      (bound radioactivity/mg nuclear protein) of L-tryptophan to hepatic nuclei in
      vitro was 74.9% (P < 0.05) lower in NZBWF1 mice than in Swiss mice. Other strains
      (DBA, SJL and BALB/c) had specific binding affinities similar to that of Swiss
      mice. Serum and hepatic free tryptophan concentrations and hepatic tryptophan
      dioxygenase activity in mice that were food-deprived overnight or 1 h after tube
      feeding L-tryptophan (20 mg/100 g body weight) were similar in the strains of
      mice. In vitro [14C] leucine incorporation into protein using hepatic microsomes
      of mice 1 h after tube-feeding L-tryptophan (20 mg/100 g body weight) revealed a
      significantly greater (P < 0.05) increase relative to food-deprived controls in
      Swiss mice (76.8 +/- 19.2%) than the increase in NZBWF1 mice (26.5 +/- 2.6%).
      Nuclear [14C]-labeled RNA release in vitro was increased 77.2 +/- 18.0% by tube
      feeding of L-tryptophan in Swiss but only 7.6 +/- 5.8% (P < 0.02) in NZBWF1 mice.
      Liver nuclear poly(A)-polymerase and nucleoside triphosphatase activities were
      variably increased by the administration of L-tryptophan in both strains. In
      summary, compared with Swiss mice, NZBWF1 mice have a lower specific binding
      affinity for L-tryptophan by hepatic nuclei, and this alteration may account for
      the other differences in responses to L-tryptophan by the two strains.

PMID- 9039828
TI  - The promoter regulatory regions of the genes for the cytosolic form of
      phosphoenolpyruvate carboxykinase (GTP) from the chicken and the rat have
      different species-specific roles in gluconeogenesis.
AB  - Hepatic expression of the gene for phosphoenolpyruvate carboxykinase (GTP) (PEPCK
      C) (EC 4.1.1.32) in birds occurs prior to birth and decreases to negligible
      levels before hatching, whereas in mammals the gene for PEPCK-C in the liver is
      expressed at birth and is active throughout the life of the animal. The
      administration of cyclic AMP to adult chickens results in the induction of
      transcription of the gene for PEPCK-C and the transient accumulation of PEPCK-C
      mRNA in the liver. DNase I footprint analysis of 330 bp of the avian PEPCK-C
      promoter immediately 5' of the start-site of transcription indicated the presence
      of several protein binding domains, purified CAAT/enhancer binding protein alpha,
      cAMP regulatory element binding protein and nuclear factor-1 bound to these
      regions of the promoter. Sequences corresponding to an hepatic nuclear factor-1
      binding domain and to the insulin response sequence, previously identified in the
      rat PEPCK-C promoter, were also found in the chicken PEPCK-C promoter. Co
      transfection of an expression vector for CAAT/enhancer binding protein alpha or
      CAAT/enhancer binding protein beta markedly stimulated transcription from both
      the chicken and rat PEPCK-C promoters in human hepatoma cells. Sequences involved
      in the regulation of gene transcription by cyclic AMP and insulin were found to
      reside between -210 and +1 of the avian PEPCK-C promoter. In general,
      transcription from the avian promoter was more sensitive to inhibition by insulin
      than was noted for the rat PEPCK-C promoter, which may explain in part the lack
      of expression of the gene for PEPCK-C in the livers of adult birds.

PMID- 9039829
TI  - The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)-ethanol
      counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells.
AB  - We investigated the injurious effects of reactive oxygen metabolites on the
      intestinal epithelium and the possible protective role played by two olive oil
      phenolic compounds, (3,4-dihydroxyphenyl)ethanol and (p-hydroxyphenyl)ethanol,
      using the Caco-2 human cell line. We induced oxidative stress in the apical
      compartment, either by the addition of 10 mmol/L H2O2 or by the action of 10 U/L
      xanthine oxidase in the presence of xanthine (250 micromol/L); after the
      incubation, we evaluated the cellular and molecular alterations. Both treatments
      produced significant decreases in Caco-2 viability as assessed by the neutral red
      assay. Furthermore, we observed a significant increase in malondialdehyde
      intracellular concentration and paracellular inulin transport, indicating the
      occurrence of lipid peroxidation and monolayer permeability changes,
      respectively. The H2O2-induced alterations were completely prevented by
      preincubating Caco-2 cells with (3,4-dihydroxyphenyl)ethanol (250 micromol/L);
      when the oxidative stress was induced by xanthine oxidase, complete protection
      was obtained at a concentration of polyphenol as small as 100 micromol/L. In
      contrast, (p-hydroxyphenyl)ethanol was ineffective up to a concentration of 500
      micromol/L. Our data demonstrate that (3,4-dihydroxyphenyl)ethanol can act as a
      biological antioxidant in a cell culture experimental model and that the ortho
      dihydroxy moiety of the molecule is essential for antioxidant activity. This
      study suggests that dietary intake of olive oil polyphenols may lower the risk of
      reactive oxygen metabolite-mediated diseases such as some gastrointestinal
      diseases and atherosclerosis.

PMID- 9039830
TI  - Serum ferritin, erythrocyte protoporphyrin and hemoglobin are valid indicators of
      iron status of school children in a malaria-holoendemic population.
AB  - In many African populations, the prevalences of both iron deficiency and malarial
      infection exceed 50%. The control of iron deficiency anemia is of urgent public
      health importance, but assessment of iron status in these contexts has been
      controversial because of the effects of malarial disease on common iron status
      indicators. We assessed iron status in 3605 school children in Zanzibar by
      measuring hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin
      concentrations. Malaria parasitemia was quantified by counting against
      leukocytes. Iron deficiency was highly prevalent: 62.4% of hemoglobin
      concentrations were <110 g/L, 59.7% of EP values were >80 micromol/mol heme, and
      41.5% of ferritin concentrations were <12 microg/L. Prevalence of Plasmodium
      falciparum parasitemia was 60.6%, but <1% of children had densities above 5000
      parasites/microL blood. Neither hemoglobin nor EP concentration was associated
      with malaria parasite density, but prevalence of abnormal values increased by <
      or = 25% with parasite density. Erythrocyte protoporphyrin and hemoglobin were
      strongly inversely related regardless of parasite density. The relationship of EP
      to hemoglobin was slightly attenuated when parasite density exceeded 1000
      parasites/microL blood. Ferritin rose by 1.5 microg/L per 1000 parasites/microL
      for parasite densities >1000 parasites/microL, but the relationship of ferritin
      to hemoglobin or EP was strong even when parasite densities exceeded this cutoff.
      The population prevalences of iron deficiency were not significantly biased by
      malarial infection. In this population of school children, iron status assessment
      using these indicators was not seriously influenced by malarial infection. We
      hypothesize that these indicators perform reliably in populations in which
      malarial infection is infrequently associated with disease; namely older children
      and adults in holoendemic environments.

PMID- 9039831
TI  - Total energy expenditure and physical activity level of lactating
      Mesoamerindians.
AB  - Energy-sparing mechanisms may be elicited to meet increased energy requirements
      imposed by lactation on women who reside in poor, rural communities in developing
      countries. The objectives of this study were to measure total energy expenditure
      and its components, basal and activity energy expenditure, and to investigate
      their relationships with lactation performance in a total of 40 rural
      Mesoamerindians stratified according to postpartum body mass index. Total energy
      expenditure and fat-free mass were measured by the doubly labeled water method,
      and basal metabolic rate was determined by indirect calorimetry at 3 and 6 mo
      postpartum. Physical activity level was taken as the ratio of total energy
      expenditure to basal metabolic rate. Milk energy output, which is not included in
      total energy expenditure, was computed from 24-h milk intake (test-weighing) and
      energy concentration of milk (bomb calorimetry). Anthropometric measurements
      revealed negligible mobilization of tissue stores. Mean (+/- SD) total energy
      expenditures were 8912 +/- 1296 kJ/d and 9253 +/- 1298 kJ/d for the lower and
      higher body mass index groups, respectively. Adjusted for fat-free mass, total
      energy expenditure was higher in the lower body mass index group (P = 0.05).
      Adjusted for fat-free mass, basal metabolic rate did not differ between groups.
      Physical activity level was significantly higher in the lower body mass index
      group (P = 0.03). Lactation performance did not differ between groups and was not
      associated with total energy expenditure or its components. Despite the
      maintenance of energy balance and heightened energy requirements of lactation,
      energy-sparing mechanisms were not evident in these lactating Mesoamerindians.

PMID- 9039832
TI  - A randomized intervention study of the effects of discontinuing coffee intake on
      growth and morbidity of iron-deficient Guatemalan toddlers.
AB  - Coffee is widely consumed by children in Guatemala. To evaluate whether coffee
      has an adverse effect on growth or morbidity, 160 children 12-24 mo of age who
      had received coffee for > or = 2 mo and had at least one indicator of iron
      deficiency were stratified by initial hemoglobin (Hb) (A = anemic vs. NA =
      "nonanemic", i.e., Hb > or = 105 g/L) and randomly assigned to a control (C =
      continuation of coffee) or intervention group (S = provided with a substitute
      consisting of sugar and coloring) for 5 mo. Anemic children were provided iron
      supplements for 2-3 mo. Hematological and anthropometric measurements were made
      before and after the intervention, and dietary and morbidity data were collected
      every 2 wk. A total of 139 children completed the intervention: 45 C-NA, 56 S-NA,
      19 C-A and 19 S-A. Compliance with the intervention was good: median coffee
      intake was 127 mL/d in group C vs. 3 mL/d in group S (P = 0.0001). There were no
      significant differences between C vs. S groups in food intake before or after the
      intervention. In the total sample, there was no effect of the intervention on
      weight or length gain. However, in children initially consuming more than 100
      mL/d of coffee (n = 96), length gain was 22% greater in the S vs. the C group (P
      = 0.07), and weight gain was 46% greater in the S-A vs. the C-A group (P < 0.05;
      NS in the NA groups). Total illness prevalence (particularly respiratory illness)
      was significantly lower in the S-NA vs. the C-NA group (P < 0.05), but somewhat
      higher in the S-A vs. the C-A group (P = 0.09). Morbidity differences did not
      explain the effect of the intervention on growth. These results indicate a modest
      increase in growth associated with discontinuation of coffee consumption by
      toddlers with initial intakes >100 mL/d.

PMID- 9039833
TI  - Age-specific determinants of stunting in Filipino children.
AB  - This study identifies age-specific factors related to new cases of stunting that
      develop in Filipino children from birth to 24 mo of age. Data come from nearly
      3000 participants in the Cebu Longitudinal Health and Nutrition Survey, a
      community-based study conducted from 1983 to 1995. Length, morbidity, feeding and
      health-related data were collected bimonthly during home visits. Stunting (length
      >2 SD below the WHO age- and sex-specific medians) occurred in 69% of rural and
      60% of urban children by 24 mo of age. We used a multivariate discrete time
      hazard model to estimate the likelihood of becoming stunted in each 2-mo
      interval. The likelihood of stunting was significantly increased by diarrhea,
      febrile respiratory infections, early supplemental feeding and low birth weight.
      The effect of birth weight was strongest in the first year. Breast-feeding,
      preventive health care and taller maternal stature significantly decreased the
      likelihood of stunting. Males were more likely to become stunted in the first
      year, whereas females were more likely to become stunted in the second year of
      life. Because stunting is strongly related to poor functional outcomes such as
      impaired intellectual development during childhood, and to short stature in
      adulthood, these results emphasize the need for prevention of growth retardation
      through promotion of prenatal care and breast-feeding, as well as control of
      infectious diseases.

PMID- 9039834
TI  - Evidence of a role for fat-free body mass in modulation of plasma carotenoid
      concentrations in older men: studies with hydrodensitometry.
AB  - We examined the relationship between body composition and changes in plasma
      carotenoid concentration in response to dietary carotenoid restriction or beta
      carotene (betaC) supplementation in healthy older men. Subjects (mean age 65 y)
      were assigned randomly to supplement (30 mg betaC/d) or placebo groups, and all
      subjects consumed a standard low carotenoid basal diet plus 1.5 mg betaC/d as
      carrots. Body composition was measured at baseline by hydrodensitometry, and
      plasma carotenoids were measured at baseline and after 28 d of treatment by HPLC.
      Baseline plasma total carotenoid concentration was significantly and negatively
      correlated with body mass index (BMI) and fat-free mass (FFM) but not with fat
      mass, whereas baseline betaC concentration was negatively associated with all
      three variables. The increase in plasma betaC concentration in response to betaC
      supplementation was significantly and inversely correlated with BMI and FFM but
      not with fat mass. Likewise, the decline in plasma total carotenoid concentration
      in the placebo group was also significantly and inversely related to BMI and FFM
      but not to fat mass. Thus, FFM seems to be an important determinant of plasma
      carotenoid concentrations and to explain a substantial portion of the often
      observed relationship between BMI and blood carotenoid levels. Fat-free mass
      seems to represent a dynamic reservoir that dampens short-term changes in plasma
      carotenoid concentrations during fluctuation in carotenoid intake.

PMID- 9039835
TI  - Production of egg proteins, enriched with L-leucine-13C1, for the study of
      protein assimilation in humans using the breath test technique.
AB  - Protein assimilation and metabolism studies are hindered by the lack of an
      adequate oral tracer, i.e., labeled proteins. We present a new and easily
      reproducible methodology for producing large amounts of egg proteins labeled with
      L-leucine-13C1. Laying hens were fed a 0.2% leucine-deficient food supplemented
      with 0.2% L-leucine-13C1 (99 atom %). At plateau, eggs containing highly enriched
      proteins were obtained. The 13C content of egg white relative to the total C
      content was 1.3371 atom %, corresponding to delta = 206%. The overall tracer
      recovery in egg proteins was high (40.2%), making this method financially
      attractive as well. Accurately measurable levels of 13CO2 in breath were obtained
      after ingestion of a physiological load of labeled egg white proteins. Thus, egg
      proteins with sufficient 13C enrichment and applicable for human protein
      assimilation and metabolism kinetic studies were produced in an easily
      reproducible and highly efficient manner.

PMID- 9039836
TI  - Diet fat saturation and feeding state modulate rates of cholesterol synthesis in
      normolipidemic men.
AB  - To determine whether diets differing in fats affect cholesterol synthesis in
      normal individuals, nine men were randomly assigned to three groups that received
      three diets in a crossover design for 2 wk. Diets were either monounsaturated
      (MONO), polyunsaturated (POLY), or saturated (SAT). Subjects then drank a dose of
      deuterium oxide, and unesterified cholesterol fractional synthesis rates (FSR)
      were calculated during consecutive fed and unfed periods. Absolute synthesis was
      calculated as the product of FSR and pool size, the latter obtained from a decay
      curve following a [4-(14)C]cholesterol injection. Serum cholesterol
      concentrations varied with each diet consumed (P = 0.001); the SAT diet produced
      the highest and the POLY diet the lowest. Triglyceride concentrations were
      highest when subjects consumed the SAT diet and lowest with the POLY diet (P =
      0.03); values obtained with the MONO diet did not differ significantly from those
      seen otherwise. HDL cholesterol concentrations were lowest when the SAT diet was
      consumed, highest when subjects were fed the MONO diet (P = 0.05), and midway but
      not significantly different with the POLY diet. Cholesterol FSR were greater when
      subjects consumed (P = 0.001) rather than not, and FSR during 12-h periods were
      greater (P = 0.045) when subjects ate the POLY diet rather than the SAT diet.
      Absolute synthesis was also greater (P = 0.04) when subjects were fed, but did
      not differ with fat type (P = 0.789). Results suggest that cholesterol synthesis
      is greater when men are fed than when they are not fed, and reduced synthesis is
      not responsible for the effect of different fats on cholesterol concentrations.

PMID- 9039837
TI  - Glucose does not facilitate the absorption of sorbitol perfused in situ in the
      human small intestine.
AB  - Sorbitol is better absorbed in the small intestine when ingested concomitantly
      with glucose. The aim of this study was to test in situ the effect of glucose on
      the absorption of sorbitol in the human small intestine, using the perfusion
      technique. The sorbitol absorption of three test solutions, perfused in a random
      order, was measured in a 30-cm segment of jejunum in six healthy volunteers (4
      males and 2 females). The solutions contained the same concentration of sorbitol
      (55 mmol/L) and increasing concentrations of D-glucose (0, 55 and 110 mmol/L).
      Net absorption of water increased as the glucose concentration of the solution
      increased and differed significantly among the three solutions. Net absorption of
      glucose was significantly greater for the 110 mmol/L glucose solution than for
      the 55 mmol/L glucose solution [23.6 +/- 1.8 vs. 11.0 +/- 1.2 mmol/(h x 30 cm), P
      < 0.01]. Sorbitol absorption in the jejunal segment was 5.2 +/- 1.3, 6.2 +/- 0.5
      and 5.8 +/- 0.4 mmol/(h x 30 cm) for the glucose-free solution, the 55 mmol/L
      glucose solution, and the 110 mmol/L glucose solution, respectively. These values
      did not differ significantly. These results do not support the hypothesis of a
      facilitating effect of glucose on sorbitol absorption in the human small
      intestine.

PMID- 9039838
TI  - Low serum vitamin B-12 concentrations are associated with faster human
      immunodeficiency virus type 1 (HIV-1) disease progression.
AB  - We conducted a nonconcurrent prospective cohort study to examine associations
      between serum concentrations of vitamin B-6, vitamin B-12 and folate and the risk
      of progression to first acquired immunodeficiency syndrome (AIDS) diagnosis and
      CD4+ cell decline to < 2 x 10(8) cells/L. The study population was drawn from a
      cohort of homosexual and bisexual men in the Baltimore-Washington, DC, area.
      Eligible subjects were human immunodeficiency virus type 1 (HIV-1)-seropositive
      at study entry and had serum available in the serum repository from their 1984
      baseline study visit. Serum micronutrient levels were assessed in 310 subjects.
      The follow-up period (April 1984 through December 1993) was approximately 9 y. In
      Kaplan-Meier analyses, participants with low serum vitamin B-12 concentrations (<
      120 pmol/L) had significantly shorter AIDS-free time than those with adequate
      vitamin B-12 concentrations (median AIDS-free time = 4 vs. 8 y, respectively, P =
      0.004). This effect persisted in Cox proportional hazards models after adjusting
      for HIV-1-related symptoms, CD4+ cell count, age, serum albumin, use of
      antiretroviral therapy before AIDS, frequency of alcohol consumption and serum
      folate concentration [relative hazard (RH) = 1.89, 95% confidence interval (CI) =
      1.15-3.10). To further explore the temporal relation between low serum vitamin B
      12 concentrations and disease progression, additional analyses were performed
      excluding subjects with more advanced disease at baseline. In these analyses, the
      increase in risk of progression to AIDS for those with low serum vitamin B-12
      concentrations remained significant (RH = 2.21, 95% CI = 1.13-4.34), providing
      further evidence that low vitamin B-12 concentrations preceded disease
      progression. In contrast, low serum concentrations of vitamin B-6 and folate were
      not associated with either progression to AIDS or decline in CD4+ lymphocyte
      count. Intervention studies are needed to determine whether correction of low
      serum vitamin B-12 concentrations in early HIV-1 infection will influence the
      natural history of disease progression.

PMID- 9039839
TI  - Roasted soybeans and an estrogenic growth promoter affect the thyroid status of
      beef steers.
AB  - We investigated the interactive effects of a roasted soybean (RSB)-supplemented
      diet and an estrogen ear implant [Synovex-S (SYN), 20 mg estradiol benzoate + 200
      mg progesterone] in young beef steers on measures of thyroid status before and
      after challenge injections of thyrotropin-releasing hormone (TRH) + growth
      hormone-releasing hormone (GHRH). Twenty steers (body weight 255 +/- 5 kg) were
      assigned to the following treatments: 1) no SYN and a soybean meal-supplemented
      diet, 2) no SYN and a RSB-supplemented diet, 3) plus SYN and soybean meal, and 4)
      plus SYN and RSB. Steers were individually fed 1.13 MJ metabolizable energy/kg
      metabolic body wt daily of an 18% protein diet. After a 5-wk growth period, all
      steers were challenged (intravenous injection) over a 3-wk period with three dose
      levels of a combination of TRH + GHRH (0.1 + 0.01, 1.0 + 0.1 and 2.5 + 0.25
      microg/kg body wt). There were no dose by SYN or RSB interactions. Across dose
      levels, values for baseline plasma thyroid-stimulating hormone (TSH) were 0.37,
      0.35, 0.61 and 0.33 microg/L for treatments 1, 2, 3 and 4, respectively (SYN, P <
      0.07; RSB, P < 0.01; SYN x RSB, P < 0.03; SEM 0.06). Net areas under the response
      curve for TSH were 66.4, 51.3, 91.4 and 64.4 (microg/L) x min, respectively (RSB,
      P < 0.08; SEM 12.0). Similar treatment effects and/or numerical differences after
      challenge were noted for thyroxine (T4) but not triiodothyronine (T3). Baseline
      (2.22 vs. 2.00 microg/L, P < 0.02) and peak (3.07 vs. 2.03 microg/L, P < 0.03) T3
      concentrations were less for steers fed RSB than for steers fed soybean meal.
      This study indicates that in young growing beef steers, SYN increases TSH release
      from the adenohypophysis and that the primary effect of RSB is reduced plasma T3,
      possibly through an effect on peripheral T4 deiodination.

PMID- 9039840
TI  - Dietary guar gum improves insulin sensitivity in streptozotocin-induced diabetic
      rats.
AB  - Although dietary recommendations for diabetics stress the need for increased
      carbohydrate and dietary fiber, the effectiveness of dietary fiber in improving
      insulin sensitivity remains controversial. The aim of this study was to compare
      the effects of a soluble fiber (guar gum) and an insoluble fiber (wheat bran) on
      insulin sensitivity in streptozotocin-induced (STZ) diabetic rats. Consequently,
      the rats were divided into two groups and one half were rendered diabetic with
      streptozotocin. The STZ diabetic and nondiabetic rats were further randomized and
      fed a diet containing dietary fiber (7 g/100 g diet) from either guar gum or
      wheat bran. The hyperinsulinemic clamp technique, combined with infusion of the
      glucose analog, 2-deoxyglucose (2DG), was utilized to examine insulin
      sensitivity. Bran-fed STZ diabetic rats were significantly (P < 0.001)
      hyperglycemic, which was ameliorated by guar gum. Insulin-mediated glucose
      disposal was increased by the guar diet compared with the bran diet in both the
      STZ diabetic rats [17.7 +/- 2.2 vs. 11.8 +/- 2.4 mL/(kg x min), P < 0.05] and the
      nondiabetic rats [20.5 +/- 2.8 vs. 15.5 +/- 1.5 mL/(kg x min), P < 0.05]. The
      accumulation of 2DG in peripheral muscles reflected the changes in insulin
      sensitivity with a trend for increased 2DG uptake in the majority of analyzed
      tissues in rats fed the guar diet, both nondiabetic and STZ diabetic, compared
      with the bran-fed rats. Accompanying these alterations in insulin sensitivity,
      guar gum suppressed food intake in the hyperphagic diabetic rats by 20% (P <
      0.001). The present results demonstrate the effectiveness of guar gum in
      improving insulin sensitivity in STZ diabetic rats and suggest that reduced food
      intake may be an important mechanism of action of guar in hyperphagic diabetic
      rats.

PMID- 9039841
TI  - The pig is an appropriate model for human biotin catabolism as judged by the
      urinary metabolite profile of radioisotope-labeled biotin.
AB  - Because the rat model of biotin deficiency and biotin metabolism has important
      limitations, we sought to determine whether the urinary profile of biotin and its
      metabolites in pigs is similar to that in humans. Biotin labeled with either 3H
      on the side chain or 14C on the ureido ring was administered intravenously to 2
      mo-old male pigs. Biotin and its metabolites were identified and quantified by
      HPLC and radiometric flow detection. At tracer doses of [3H]biotin, 12 +/- 6%
      (mean +/- SD, n = 3) of total administered radioactivity was excreted within 72
      h; at a physiologic dose of [14C]biotin, 47 +/- 2% (n = 5) of the administered
      radioactivity was excreted within 72 h. Biotin was the major form excreted, as it
      was in humans. Substantial amounts of bisnorbiotin and biotin sulfoxide, two
      known biotin metabolites, were also excreted. Bisnorbiotin methyl ketone and
      biotin sulfone, two biotin metabolites recently identified in human urine, were
      also present in pig urine. This study provides evidence that biotin metabolism in
      pigs resembles that in humans.

PMID- 9039842
TI  - Diet-induced changes in liver and bile but not brain fatty acids can be predicted
      from differences in plasma phospholipid fatty acids in formula- and milk-fed
      piglets.
AB  - The fatty acid composition of plasma phospholipids differs between infants fed
      formula and infants fed human milk, but the extent to which this is accompanied
      by differences in tissue phospholipid fatty acids is unclear. This paper
      describes analysis of plasma, liver and brain fatty acids from piglets fed one of
      seven formulas, varying in saturated, monounsaturated, (n-6) and (n-3) fatty
      acids or sow milk from birth for 18 d. Bile fatty acids were analyzed because
      they are secreted from liver and may be an important source of fatty acids for
      intestinal lipoprotein synthesis. The results were used to determine the relation
      between diet-related differences in plasma phospholipid fatty acids and those in
      brain, liver and bile. Where significant associations were found, prediction
      limits were constructed to assess the usefulness of analysis of plasma
      phospholipid fatty acids to predict diet-induced changes in tissue fatty acids.
      The proportions (g/100 g fatty acids) of 16:0, 18:0, 18:1, 18:2(n-6) and 20:4(n
      6) in plasma phospholipids were significantly associated with the proportions of
      the same fatty acids in liver and bile, but not brain. The results show a
      reasonably precise, predictable association between plasma and liver, and plasma
      and bile fatty acids. Brain 20:4(n-6) and 22:6(n-3), in contrast, were not
      reliably associated with plasma phospholipid 20:4(n-6) and 22:6(n-3) for piglets
      fed milk or formula providing about 1.5% energy as 18:3(n-3).

PMID- 9039843
TI  - Some algae are potentially adequate sources of vitamin B-12 for vegans.

PMID- 9039844
TI  - Some algae are potentially adequate sources of vitamin B-12 for vegans.

PMID- 9039845
TI  - Defective myogenesis in NFB-s mutant associated with a saturable suppression of
      MYF5 activity.
AB  - Myogenic cell lines have proved to be useful tools for investigating the
      molecular mechanisms that control cellular differentiation. NFB-s is a mutant
      myogenic cell line which fails to differentiate in vitro, and can repress
      differentiation in normal myogenic cells when fused to form heterokaryons. The
      NFB-s cell line was used here to study the molecular mechanisms underlying such
      myogenic repression. Using muscle-specific reporter genes, we show that NFB-s
      cells fail to activate fully the muscle differentiation program at a
      transcriptional level, although muscle-specific transcription can be enhanced by
      regulators of differentiation such as pertussis toxin. Paradoxically we find that
      the myogenic regulator myf5 is expressed at constitutively high levels in NFB-s
      cells, and retains DNA binding activity. Expression plasmids encoding NFB-derived
      myf5 cDNA can rescue the myogenic phenotype in NFB-s cells, demonstrating that a
      threshold level of positive regulators must be reached before the myogenic
      program is activated. Thus, the dominant negative phenotype does not appear to
      result from defective myf5, but is due to a dosage-dependent saturable mechanism
      that interferes with myf5 function. These studies demonstrate that the
      stoichiometric ratio of positive and negative regulators is critical for
      determining the myogenic differentiation state.

PMID- 9039846
TI  - Myoblast-mediated expression of colony stimulating factor-1 (CSF-1) in the
      cytokine-deficient op/op mouse.
AB  - The osteopetrotic (op/op) mouse lacks colony stimulating factor-1 (CSF-1) due to
      an inactivating mutation in the CSF-1 gene. Intramuscular transplantation of
      engineered myoblasts was used to introduce CSF-1 into the circulation of op/op
      mice. The CSF-1 cDNA was introduced into C2C12 mouse myoblasts in culture using
      retroviral mediated gene transfer. Upon transplantation into the skeletal muscle
      of mutant mice, physiological levels of the cytokine were achieved systemically
      and elicited a biological response: circulating monocytes were induced. Howvever,
      both circulating CSF-1 levels and the induction of monocytes were transient.
      Analysis of the site of cell transplantation revealed local changes that may
      account for the transience of serum cytokine levels. Macrophage markers were
      induced in muscle tissue implanted with CSF-1 expressing myoblasts: c-fms, the
      CSF-1 receptor as well as the lineage-restricted antigen F4/80. We propose that
      in addition to CSF-1 clearance by Kupffer cells of the liver, macrophages that
      accumulated at the site of cell transplantation bound the CSF-1 produced by the
      muscle cell transplants, precluding the sustained release of this cytokine into
      the systemic circulation. Our studies also revealed that damage to muscle caused
      during cell transplantation or by freeze injury resulted in the accumulation of
      macrophages in op/op mouse muscle tissue. Indeed, op/op mice were fully capable
      of regenerating injured muscle suggesting the presence of as yet unidentified CSF
      1-independent factors capable of generating macrophages that presumably
      participate in tissue remodeling in this cytokine-deficient mouse.

PMID- 9039847
TI  - Genes transfected into embryonal carcinoma stem cells are both lost and
      inactivated at high frequency.
AB  - Embryonal carcinoma (EC) cells can be efficiently transfected with cloned DNAs
      but there is a strong tendency for expression from transfected genes to be lost
      from stably transformed cells. To investigate the mechanism responsible for this
      loss of expression, we transfected P19 EC cells with a gene encoding the E. coli
      beta-galactosidase and examined expression of this gene in clonal populations of
      cells. Cells that carry and express the beta-galactosidase gene give rise to
      cells that do not express at a rate of about 0.02 events per cell per cell
      division. These non-expressing cells were of two types, some had lost the
      transfected genes while others had inactivated them. In those cells that retained
      but inactivated the transfected genes, the inactive state was stable and
      suppression was at the level of transcription initiation but not associated with
      increased DNA methylation. Because transfected DNAs integrate into the genome as
      tandem arrays, the gene loss and inactivation seen in EC cells may be analogous
      to the repeat-induced gene inactivation seen in lower eukaryotes.

PMID- 9039848
TI  - Roberts syndrome fibroblasts showing cisplatin hypersensitivity have normal host
      cell reactivation of cisplatin-treated adenovirus and normal capacity of
      cisplatin-treated cells for adenovirus DNA synthesis.
AB  - Roberts syndrome (RS) is a rare, recessively inherited disorder characterized by
      growth retardation, limb reductions and craniofacial deformities. Cells from a
      subset of afflicted individuals, termed RS+, display unusual separation or
      puffing of the heterochromatic regions of their chromosomes and are
      hypersensitive to several DNA-damaging agents including mitomycin C (MMC) and
      cisplatin, both of which can induce interstrand crosslinks in DNA. For this
      reason, we have investigated the ability of RS+ fibroblasts to repair cisplatin
      induced DNA lesions using adenoviris as a probe. Host cell reactivation of
      cisplatin-treated adenovirus (Ad) was significantly reduced in nucleotide
      excision repair (NER)-deficient xeroderma pigmentosum (XP) cells but was normal
      in the two RS+ fibroblast strains and the Fanconi's anemia (FA)fibroblast strain
      tested. The capacity of cisplatin-treated cells for Ad DNA synthesis was reduced
      in XP and FA cells compared to normal human cells, but was not reduced in RS+
      cells. These results indicate that the hypersensitivity of RS+ cells to cisplatin
      is not due to a deficiency in NER nor due to a deficiency in the pathway which
      leads to cisplatin hypersensitivity in FA cells. It is possible that the abnormal
      heterochromatin organisation of RS+ cells selectively renders the heterochromatic
      regions of the genome more susceptible to mutagen damage and/or less available
      for repair.

PMID- 9039849
TI  - Evidence that heteronuclear proteins interact with XIST RNA in vitro.
AB  - The process of X chromosome inactivation results in the transcriptional silencing
      of one of the two X chromosomes in mammalian females. A large heterogeneous
      nuclear RNA that is expressed exclusively from the inactive X chromosome (XIST--X
      Inactive Specific Transcripts) has been implicated in the inactivation process.
      The XIST RNA colocalizes with the inactive X chromosome and therefore proteins
      that interact with the XIST RNA may be involved in the inactivation of the X
      chromosome. In order to identify such proteins we have used an in vitro UV light
      cross-linking technique to detect nuclear proteins associating with sections of
      the XIST RNA. The strongest interaction detected by this technique was between a
      pair of approximately 40 kDa proteins and a 5' region of the XIST RNA which
      contains a series of well-conserved tandem repeats. Immunoprecipitation suggested
      that these proteins may be the heteronuclear proteins hnRNPC1/C2.

PMID- 9039850
TI  - Structural characterization and fine chromosomal mapping of the human P2Y1
      purinergic receptor gene (P2RY1).
AB  - Using P2Y1 specific oligonucleotide primers in a Polymerase Chain Reaction on
      human genomic DNA, we have amplified a region encoding the P2Y1 receptor
      Restriction analysis and Southern hybridization of the PCR product revealed that
      the entire open reading frame of the human P2Y1 receptor is coded by an
      intronless gene. We have previously localized the P2Y1 receptor gene to human
      chromosome 3. The gene was further localized to a region of chromosome 3 using a
      subchromosomal hybrid panel containing different segments of chromosome 3. Based
      on the specific PCR product obtained and its Southern hybridization to the human
      P2Y1 receptor cRNA, the P2Y1 receptor gene was mapped to human chromosome 3q25.

PMID- 9039851
TI  - Chromosomal localization of 15 ion channel genes.
AB  - Several human Mendelian diseases, including the long-QT syndrome, malignant
      hyperthermia, and episodic ataxia/myokymia syndrome, have recently been
      demonstrated to be due to mutations in ion channel genes. Systematic mapping of
      ion channel genes may therefore reveal candidates for other heritable disorders.
      In this study, the GenBank and dbEST databases were used to identify members of
      several ion channel families (voltage-gated calcium and sodium, cardiac chloride,
      and all classes of potassium channels). Genes and ESTs without prior map
      localization were identified based on GDB and OWL database information and 15
      genes and ESTs were selected for mapping. Of these 15, only the serotonin
      receptor 5HT3R had been previously mapped to a chromosome. A somatic cell hybrid
      panel (SCH) was screened with an STS from each gene and, if necessary the results
      verified by a second SCH panel. For three ESTs, rodent derived PCR products of
      the same size as the human STS precluded SCH mapping. For these three, human P1
      clones were isolated and the genomic location was determined by metaphase FISH.
      These genes and ESTs can now be further evaluated as candidate genes for
      inherited cardiac, neuromuscular and psychiatric disorders mapped to these
      chromosomes. Furthermore, the ESTs developed in this study can be used to isolate
      genomic clones, enabling the determination of each transcript's genomic structure
      and physical map location. This approach may also be applicable to other gene
      families and may aid in the identification of candidate genes for groups of
      related heritable disorders.

PMID- 9039852
TI  - Time-dependent sensitization of heart rate and blood pressure over multiple
      laboratory sessions in elderly individuals with chemical odor intolerance.
AB  - In this study, we tested the hypothesis that low-level chemical odor intolerance
      (i.e., "cacosmia") is a manifestation of heightened sensitizability to
      environmental stimuli. We examined supine heart rate and blood pressure of
      elderly individuals, who were classified as either having a higher degree of
      chemical odor intolerance (n = 12) or a lower degree of chemical odor intolerance
      (n = 13), upon awakening in a sleep research laboratory on 6 different days
      during an 8-wk protocol. During the 2 initial wk, they consumed a customary
      baseline diet (including ad lib milk and other dairy products), followed by 3 wk
      each of nondairy-containing and dairy-containing diets in randomly assigned,
      counterbalanced order. Measurements were made on 3 pairs of successive days,
      distributed over a 6-wk period, and on which different diets were consumed. The
      high-intolerance group had significantly higher mean supine systolic and
      diastolic blood pressures than did the low-intolerance group. Although subjects
      consumed milk products during both the initial baseline and subsequent dairy diet
      periods, the high-intolerance group had significantly higher heart rates and
      diastolic blood pressures later in the study than at baseline, especially when
      they were on the dairy diet. In contrast, the cardiovascular measures of the low
      intolerance group lowered on average with time. The high-intolerance subjects had
      an increased mean diastolic blood pressure on the second days versus the first
      days in the laboratory (averaged across all diets). Collectively, the data
      suggest that elderly individuals with a high degree of chemical odor intolerance
      evidence (a) increased sympathetic tone in the cardiovascular system at rest over
      multiple measurements; and (b) greater sensitizability and/or lesser habituation
      of heart rate and diastolic blood pressure over time as a function, in part, of
      repeated environmental stressor exposures (i.e., a novel laboratory contextual
      setting and/or specific dietary constituents). Consistent with a sensitization
      model, the findings emphasize the need for two or more identical sessions at
      least 24 h apart in physiological studies of individuals with a high degree of
      intolerance for chemical odors versus normal individuals. The results of the
      blood pressure observations suggest that the possibility of abnormally labile
      autonomic function and cognitive sequelae in individuals with a high degree of
      intolerance for chemical odor increases with age.

PMID- 9039853
TI  - Responses of older men with and without chronic obstructive pulmonary disease to
      prolonged ozone exposure.
AB  - We tested responses to ozone (O3) under simulated "worst-case" ambient exposure
      conditions. Subjects included 9 men who had severe chronic obstructive pulmonary
      disease (COPD) with subnormal carbon monoxide diffusing capacity (i.e., an
      emphysemic component) and 10 age-matched healthy men. Each subject was exposed to
      0.24 ppm O3 and to clean air (control) in an environmentally controlled chamber
      at 24 degrees C and 40% relative humidity. Exposures were randomized, they
      occurred 1 wk apart, and they lasted 4 h. During each half-hour interval, light
      exercise occurred (i.e., average ventilation 20 l/min) for 15 min. During both
      control and O3 exposures, group mean symptom intensity and specific airway
      resistance (SRaw) increased, whereas forced expiratory performance decreased. The
      healthy subgroup's mean arterial oxygen saturation (SaO2) rose slightly, and the
      COPD subgroup's mean SaO2 declined slightly, during exercise. Group mean forced
      expiratory volume in 1 s (FEV1.0) declined significantly in O3 exposures,
      compared with controls (p approximately .01). Mean excess FEV1.0 loss after 4 h
      in O3 (relative to control) was 8% of the preexposure value in the COPD subgroup,
      compared with 3% in the healthy subgroup (p > .05 [nonsignificant]). Overall
      FEV1.0 loss during O3 exposures, including exercise effects, averaged 19% in the
      COPD subgroup, compared with 2% in the healthy subgroup (p < .001). Symptoms,
      SRaw, and SaO2 responses, as well as healthy subjects' postexposure bronchial
      reactivity, differed little between O3-exposed and control subjects. We therefore
      concluded that in older men with or without severe COPD, O3 causes lung
      dysfunction under "worst-case" ambient exposure conditions, despite older
      subjects' comparative unresponsiveness to O3. The combined effect of O3 and
      exercise on lung dysfunction is markedly greater with COPD. It is still unclear
      whether COPD causes an increased response to O3 per se.

PMID- 9039854
TI  - Time dependence of blood concentrations during and after exposure to a mixture of
      volatile organic compounds.
AB  - Volatile organic compounds constitute a group of important environmental
      pollutants that have been associated with the constellation of symptoms known as
      sick building syndrome. An understanding of the kinetics of uptake and
      elimination of volatile organic compounds is important for the proper
      interpretation of the internal dose concentrations of people exposed to these
      compounds. Blood concentrations measured before, during, and after exposure of
      five individuals to a mixture of volatile organic compounds in a controlled
      chamber are described. Blood concentrations were related directly to air exposure
      concentrations and appeared to be a function of the blood/air partition
      coefficient. The half-lives of the internal dose of the volatile organic
      compounds measured were less than 1/2 h, but the elimination time courses were
      multiexponential. The complexity of the elimination curve suggested the existence
      of multiple storage sites within the body. The presence of a long-term
      exponential in the blood elimination curve suggested that, with repeated
      exposure, bioaccumulation may occur in humans.

PMID- 9039855
TI  - Attenuated response to repeated daily ozone exposures in asthmatic subjects.
AB  - The development of attenuated response ("tolerance") to daily ozone (O3)
      exposures in the laboratory is well established in healthy adult volunteers.
      However, the capability of asthmatics to develop tolerance during multiday ozone
      exposures is unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm
      O3 in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air
      exposures during the preceding week served as controls. Follow-up O3 exposures
      were performed 4 and 7 d after the most recent consecutive exposure. All
      exposures were performed in an environmental chamber at 31 degrees C and 35%
      relative humidity. The subjects performed moderate exercise (mean ventilation
      rate of 32 l/min) for 15 min of each half-hour. Responses were measured with
      spirometry and symptom evaluations before and after each exposure, and a
      bronchial reactivity test (methacholine challenge) was conducted after each
      exposure. All response measurements showed clinically and statistically
      significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s
      responses were similarly large on the 1st and 2nd O3 exposure days, after which
      they diminished progressively, approaching filtered air response levels by the
      5th consecutive O3 day. This tolerance was partially lost 4 and 7 d later.
      Bronchial reactivity peaked after the first O3 exposure and remained somewhat
      elevated after all subsequent O3 exposures, relative to its control level
      following filtered-air exposures. Individual responses varied widely; more severe
      initial responses to O3 predicted less rapid attenuation. We concluded that
      asthmatics can develop tolerance to frequent high-level O3 exposures in much the
      same manner as normal subjects, although the process may be slower and less fully
      effective in asthmatics.

PMID- 9039856
TI  - Prevalence of congenital deficiency in serum cholinesterase.
AB  - The most economical blood test for the monitoring of workers who are exposed to
      organophosphate pesticides is serum cholinesterase; however, serum cholinesterase
      can be affected by conditions other than pesticide exposure. The results of
      studies in Europe indicate a 4% prevalence of congenital serum cholinesterase
      deficiency. Prevalence rates in the United States have not been reported. In this
      study, 127 workers who were part of an employee health program were evaluated.
      Workers who had decreased serum cholinesterase levels on baseline testing before
      pesticide exposure were evaluated for a congenital deficit in serum
      cholinesterase. Five (3.9%) individuals had baseline measurements below the
      laboratory normal reference value: 4 (3.1 %) were heterozygote for the
      deficiency, and the remaining individual did not return to test for the genetic
      deficiency. No one was found to have the homozygote deficiency. The prevalence of
      congenital deficiency in serum cholinesterase in a midwestern population was 3.1
      3.9%. We found it useful to incorporate the knowledge of who has a congenital
      deficiency into our employee health program, the purpose of which is to monitor
      workers who spray organophosphates.

PMID- 9039857
TI  - Auditory effects of aircraft noise on people living near an airport.
AB  - Two groups of randomly chosen individuals who lived in two communities located
      different distances from the airport were studied. We monitored audiometry and
      brainstem auditory-evoked potentials to evaluate cochlear and retrocochlear
      functions in the individuals studied. The results of audiometry measurements
      indicated that hearing ability was reduced significantly in individuals who lived
      near the airport and who were exposed frequently to aircraft noise. Values of
      pure-tone average, high pure-tone average, and threshold at 4 kHz were all higher
      in individuals who lived near the airport, compared with those who lived farther
      away. With respect to brainstem auditory-evoked potentials, latencies between the
      two groups were not consistently different; however, the abnormality rate of such
      potentials was significantly higher in volunteers who lived near the airport,
      compared with less-exposed counterparts. In addition, a positive correlation was
      found between brainstem auditory-evoked potential latency and behavioral hearing
      threshold of high-frequency tone in exposed volunteers. We not only confirmed
      that damage to the peripheral cochlear organs occurred in individuals exposed
      frequently to aircraft noise, but we demonstrated involvement of the central
      auditory pathway.

PMID- 9039858
TI  - High blood lead levels in ceramic folk art workers in Michoacan, Mexico.
AB  - Ceramic folk art workers are at risk for developing lead intoxication. These
      workers live in small settlements, which often lack sanitation services, and
      these individuals work with ceramics in their homes. The study population
      comprised individuals of all ages from three rural communities in central
      Michoacan (Tzintzuntzan, Tzintzunzita, and Colonia Lazaro Cardenas). A survey
      questionnaire, which was provided to each individual, included questions about
      household characteristics, presence of a clay oven in the home, and use of lead
      oxide ("greta") and other hazardous products. Venous blood samples were obtained
      from the workers. We found lead exposure to be reduced if the home floor was
      covered and if the house had been painted < or =1 y prior to study. Blood lead
      levels exceeded the maximum level permitted, but the levels were lower than those
      found in the 1970s, during which time study techniques for analyzing samples
      differed from those used in the present study. In addition, activity patterns of
      the populations differed during the two studies.

PMID- 9039859
TI  - Pulmonary functions of school children in highly polluted northern Bohemia.
AB  - The purpose of this study was to ascertain whether pulmonary function in children
      who were lifetime residents of the highly polluted district of Teplice in
      northern Bohemia was lower than that for children who were lifetime residents of
      the cleaner district of Prachatice in southern Bohemia. Forced expiratory
      spirometry was measured twice (February/March and April) in approximately 235
      eighth-grade students in each district. On both testing occasions, height
      adjusted forced expiratory volume in 1 s and forced expiratory flow between 25%
      and 75% forced vital capacity were significantly lower (p < .001) in children
      from Teplice than in those from Prachatice. These differences were not associated
      with parental smoking habits, presence of pets, heating/cooking fuels, private
      home/apartment residency, or rural/urban residency. In Teplice, no differences
      were observed between lung functions measured at the end of the high pollution
      season (February/March) and those measured after the children breathed much
      cleaner air for a 4-wk period (April). This result was suggestive of a condition
      of chronically depressed lung function. No differences across times were observed
      in Prachatice, indicating that our measurements were reliable.

PMID- 9039860
TI  - Mental strain and physical symptoms among employees in modern offices.
AB  - A comprehensive questionnaire that assessed both physical and psychosocial work
      environments, as well as personal health and lifestyle, was answered by 133 (92%)
      employees. In addition, we assessed the physical/chemical and psychosocial
      environments of 8 randomly selected employees, of whom some had environmentally
      related health complaints. Environmental factors most often associated with poor
      work environments were improper room temperature, light reflexes (i.e., glare and
      reflection of light), dust, and dry air. Emission products from traffic pollution
      and 1,1,1-trichloroethane levels were also detected. The electromagnetic fields
      in both the low and the extremely low frequencies spectra were close to
      background levels. Individuals who had environmentally associated health symptoms
      worked mainly in the customer support division, and they perceived higher work
      demands. Their computer environment was also worse ergonomically. There were no
      differences with respect to objective skin signs or disease between those with
      and without symptoms, respectively. The results of this study point to the
      importance of looking at both the psychosocial and physical environments when
      health complaints arise in modern offices.

PMID- 9039861
TI  - Dampness and respiratory symptoms among workers in daycare centers in a
      subtropical climate.
AB  - We evaluated the association between measures of dampness in daycare centers (N =
      56) in the Taipei area and symptoms of respiratory illness in 612 employees.
      Dampness was found in 75.3% of the centers, visible mold in 25.8%, stuffy odor in
      50.0%, water damage in 49.3%, and flooding in 57.2%. Furthermore, prevalence of
      sick building syndrome symptoms in the daycare workers was statistically
      significant among those who worked in centers that had mold or dampness. Also,
      the observed numerous incidences of dampness or mold in centers were very common
      in this subtropical region, and dampness was a strong predictor of sick building
      syndrome symptoms.

PMID- 9039863
TI  - East meets west to cure Russia's ills.

PMID- 9039862
TI  - Airborne fungus allergen in association with residential characteristics in
      atopic and control children in a subtropical region.
AB  - Airborne fungi were collected during the summer and winter seasons. A N6 Andersen
      sampler was used inside and outside the homes of 46 asthmatic children, 20 atopic
      children, and 26 nonatopic control children in the Taipei area. In addition, host
      and house characteristics were obtained by questionnaire. The indoor fungus
      concentrations of asthmatic and control groups were higher than those in atopic
      groups in summer, but there were no differences in total fungus concentrations
      among three groups in winter. Concentration differences among these three groups
      also occurred for Cladosporium and Penicillium in summer and for Aspergillus,
      Cladosporium, Penicillium, and yeast in the winter. Moreover, it was demonstrated
      that no differences in fungus concentration were observed between damp and dry
      homes. Penicillium concentrations appeared to be related to home dampness. Home
      dampness was associated with allergic symptoms in children with asthma and
      rhinitis. An association was also observed between the occurrence of Cladosporium
      and history of asthma.

PMID- 9039864
TI  - The art of 'HAART': researchers probe the potential and limits of aggressive HIV
      treatments.

PMID- 9039865
TI  - Is bigger better for retrovirus conference?

PMID- 9039866
TI  - Military physicians face new challenges as Bosnia peacekeeping effort lengthens.

PMID- 9039867
TI  - From the Centers for Disease Control and Prevention. FDA approval for infants of
      a Haemophilus influenzae type b conjugate and hepatitis B (recombinant) combined
      vaccine.

PMID- 9039868
TI  - From the Centers for Disease Control and Prevention. Antibiotic resistance among
      nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae-
      Bangui, 1995.

PMID- 9039870
TI  - Does this patient have appendicitis?

PMID- 9039869
TI  - Does this patient have appendicitis?

PMID- 9039871
TI  - Does this patient have appendicitis?

PMID- 9039872
TI  - Does this patient have appendicitis?

PMID- 9039873
TI  - Does this patient have appendicitis?

PMID- 9039874
TI  - Hepatitis C virus and intravenous immune globulin.

PMID- 9039875
TI  - Hepatitis C virus and intravenous immune globulin.

PMID- 9039876
TI  - Radiologists' interpretations: the problem of context bias.

PMID- 9039877
TI  - Highly drug-resistant tuberculosis.

PMID- 9039878
TI  - Smoking and risk of cryptococcosis in patients with AIDS.

PMID- 9039879
TI  - Elevated glutamate in the cerebrospinal fluid of patients with HIV dementia.

PMID- 9039880
TI  - Impact of measurement and feedback on vaccination coverage in public clinics,
      1988-1994.
AB  - OBJECTIVE: To investigate whether a reported rise in vaccination coverage in
      Georgia public clinics during the period 1988 through 1994 was artifactual or
      real and, if real, to determine the extent to which the rise could be associated
      with a program of measurement and feedback. DESIGN: Examination of data from
      Georgia public clinics, doses-administered records, and National Health Interview
      Surveys. SETTING/PARTICIPANTS: Children attending Georgia public clinics.
      INTERVENTION: Measurement of vaccination coverage and feedback to providers. MAIN
      OUTCOME MEASURE: Vaccination coverage rates. RESULTS: For the period 1988 through
      1994, 136 004 Georgia public clinic vaccination records for children 21 to 23
      months of age were reviewed. Median series-completion rates at public clinics
      rose from 53% to 89%, while indexes of under-vaccination fell: missed
      opportunities for simultaneous vaccination (6% to 0%), lost contact for more than
      12 months (14% to 1%), and first vaccination more than 1 month late (19% to 8%).
      According to the independent doses-administered database, the proportion of
      children starting the primary series very late (> or =12 months old) fell from
      14% to 6%, and the series-completion index rose from 64% to 83%, suggesting that
      improvements could not be wholly ascribed to better clinic record keeping. In
      1988, vaccination coverage of children 24 months of age in the National Health
      Interview Survey (NHIS) was 53%, identical to median public clinic coverage in
      Georgia; in 1993, NHIS coverage was 60%, while median public clinic coverage in
      Georgia was 90%, suggesting that the rise in coverage in Georgia public clinics
      exceeded national trends. Patterns within the coverage changes suggest an
      association with the process of measurement and feedback. CONCLUSIONS: A marked
      increase in vaccination coverage occurred in Georgia public clinics associated
      with a program of annual measurement and feedback.

PMID- 9039881
TI  - Medicaid enrollment and health services access by Latino children in inner-city
      Los Angeles.
AB  - OBJECTIVES: To understand the role of parental immigration status on Medicaid
      enrollment and access to health services for young Latino children. DESIGN: A
      cross-sectional household survey of the parents of inner-city Latino children.
      SETTING: South Central and East Los Angeles, Calif, 1992. POPULATION: Children 12
      to 36 months old and their parents from 817 Latino families. MAIN OUTCOME
      VARIABLES: Continuous Medicaid enrollment, continuity of care, deferral of care,
      and number of visits. METHODS: Univariate analysis, logistic and linear
      regression by demographic and socioeconomic characteristics, residency status,
      and language use. RESULTS: Children were primarily born in the United States
      (96%), but most parents were not citizens (80%). Only 40.0% of eligible children
      had continuous Medicaid coverage since birth, 18.6% had never been insured, and
      20.7% had received episodic Medicaid coverage. Continuous Medicaid coverage was
      negatively associated with either the caregiver (odds ratio [OR],0.32; 95%
      confidence interval [CI], 0.19-0.56) or their partner (OR=0.33, 95% CI =0.20
      0.55) working. Residency status, language preference, and length of US residency
      were not associated with continuous Medicaid enrollment. Insurance coverage was
      associated with more physician visits, greater continuity of care, and fewer
      deferrals of care. CONCLUSION: While most (84%) young Latino children in inner
      city Los Angeles were eligible for Medicaid, a substantial proportion (39.3%)
      have episodic or no coverage. Insurance status and provider type were more
      consistently associated with access rather than residency and language
      preference. In the aftermath of California's Proposition 187 and federal welfare
      reform, insurance status and access are likely to worsen for these young children
      unless the wave of antiimmigration sentiments is held in check.

PMID- 9039882
TI  - A prospective study of risk factors for pulmonary embolism in women.
AB  - OBJECTIVE: To investigate risk factors for pulmonary embolism in women. DESIGN:
      Prospective study based on biennial, mailed questionnaires. SETTING: Nurses'
      Health Study with 16 years of follow-up from 1976 to 1992. PATIENTS: A group of
      112822 women aged 30 to 55 years in 1976, free from diagnosed cardiovascular
      disease or cancer at baseline. Overall, there were 1619770 person-years of follow
      up. MEASUREMENTS: Based on self-report and medical records, we documented 280
      cases of pulmonary embolism, of which 125 were primary (no identified antecedent
      cancer, trauma, surgery, or immobilization). Information on height, weight,
      cigarette smoking, hypertension, diabetes, and hypercholesterolemia was collected
      by questionnaire. RESULTS: In multivariate analysis, obesity, cigarette smoking,
      and hypertension were independent predictors of pulmonary embolism. Specifically,
      obese women (body mass index > or = 29.0 kg/m2) had an increased risk of primary
      pulmonary embolism (multivariate relative risk=2.9; 95% confidence interval [CI],
      1.5-5.4). Heavy cigarette smokers also had an increased risk of primary pulmonary
      embolism. The relative risk (RR) of primary pulmonary embolism was 1.9 (95% CI,
      0.9-3.7) for women currently smoking 25 to 34 cigarettes per day and 3.3 (95% CI,
      1.7-6.5) for those smoking 35 cigarettes or more daily as compared with never
      smokers. Hypertension, even after adjustment for body mass index, was also
      associated with an increased risk of primary pulmonary embolism (RR=1.9; 95% CI,
      1.2-2.8). High serum cholesterol levels (RR=1.1; 95% CI, 0.62-1.8) and diabetes
      (RR=0.7; 95% CI, 0.3-1.9) did not appear to be related to primary pulmonary
      embolism. CONCLUSION: These prospective data indicate that obesity, cigarette
      smoking, and hypertension are associated with increased risk of pulmonary
      embolism in women. Control of these risk factors will decrease risks of pulmonary
      embolism as well as coronary heart disease.

PMID- 9039883
TI  - Relationship of preoperative antiendotoxin core antibodies and adverse outcomes
      following cardiac surgery.
AB  - OBJECTIVE: To test the hypothesis that low serum antiendotoxin core antibody
      (EndoCAb) level is an independent predictor of adverse outcome following cardiac
      surgery. DESIGN: Prospective, blinded, cohort study. SETTING: Tertiary care
      medical center. SUBJECTS: A total of 301 patients undergoing coronary artery
      bypass graft surgery and/or valvular heart surgery. DESIGN: Preoperative serum
      was assayed for IgM EndoCAb, IgG EndoCAb, total IgM, and total IgG levels. Known
      preoperative risk factors were assessed, and patients were assigned a risk score
      using a validated method. MAIN OUTCOME MEASURE: A major complication, defined as
      either in-hospital death or postoperative length of stay greater than 10 days.
      RESULTS: Overall, a major complication occurred in 34 patients (11.3%). Lower IgM
      EndoCAb level independently predicted (P=.002) increased risk of major
      complication over and above the effects of preoperative risk score (P=.02), total
      IgG level (P=.07), and all other known perioperative risk factors. In contrast,
      IgG Endo-CAb and total IgM concentrations did not predict outcome. No association
      existed between risk score and level of IgM EndoCAb. CONCLUSION: There is marked
      preoperative variability in humoral immunity against endotoxin core, which is not
      accounted for by differences in known preoperative risk factors. In this study,
      low levels of IgMEndoCAb were an important independent predictor of adverse
      postoperative outcome, which supports the theory that endotoxemia is a cause of
      postoperative morbidity.

PMID- 9039884
TI  - Managing the interface between medical schools, hospitals, and clinical research.
AB  - OBJECTIVE: To review how academic health centers are coping with the changing
      environment of health care delivery with special emphasis on the impact of the
      changing health care system on clinical research. DESIGN: In response to Health
      and Human Services Secretary Donna Shalala's 1995 mandated review of the National
      Institutes of Health (NIH) Warren Grant Magnuson Clinical Center, an NIH review
      team visited 30 health facilities and government-owned organizations throughout
      the country. The review team determined what strategies are used by academic
      health centers to survive and thrive in the changing health care marketplace. The
      findings have implications for the NIH Clinical Center as well as academic health
      centers. CONCLUSIONS: Management strategies in successful academic health centers
      include streamlined governance structures whereby small groups of highly
      empowered group leaders allow institutions to move quickly and decisively; an
      active strategic planning process; close integration of hospital and medical
      school management; heavy investment in information systems; and new structures
      for patient care delivery. Successful centers are initiating discussions with
      third-party payers and are implementing new initiatives, such as establishing
      their own managed care organizations, purchasing physician practices, or owning
      hospitals. Other approaches include establishing revenue-generating centers for
      clinical research and new relations with industry. Attention to the
      infrastructure required to support the training and conduct of clinical research
      is essential for the future vitality of medical schools.

PMID- 9039885
TI  - Relationship of microbiologic diagnostic criteria to morbidity and mortality in
      patients with ventilator-associated pneumonia.
AB  - OBJECTIVE: To evaluate whether the mortality and the morbidity of ventilator
      associated pneumonia, defined by positive result of protected specimen brush
      culture, was different from that defined by other methods. DESIGN: Matched-cohort
      study. All patients with clinical suspicion of pneumonia were investigated with
      protected specimen brush, bronchoalveolar lavage, and blind bronchial samplings.
      Two groups were defined: brush-positive patients (positive culture of the
      protected specimen brush) and brush-negative patients (negative culture of the
      protected specimen brush, but positive culture with another method). SETTING: A
      14-bed medicosurgical intensive care unit (ICU) in an 850-bed teaching hospital.
      PATIENTS: All patients with documented ventilator-associated pneumonia over 4
      years 9 months. A total of 102 cases documented by protected specimen brush
      culture and 223 documented by another sampling procedure. Patients were matched
      according to diagnosis on admission, age, sex, date of admission, Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score, and date of onset
      of pneumonia. MAIN OUTCOME MEASURES: Mortality rate, duration of mechanical
      ventilation, duration of ICU stay, duration of hospital stay, sampling methods,
      and microbiologic cultures. RESULTS: A total of 76 pairs were submitted for
      analysis. The effectiveness of matching was 81.85%. There was no difference in
      mortality between brush-positive patients and brush-negative patients. The ICU
      fatality rate was 38% in the brush-positive group and 39.4% in the brush-negative
      group (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.46-1.93). The
      hospital fatality rate was 41% (OR, 1; 95% CI, 0.5-2.01). The mean (SD) duration
      of ventilation was 26 (23) days in the 2 groups (range, 3-132 days). The duration
      of ICU stay was 33 (27.4) days in the 2 groups (range, 3-152 days). CONCLUSIONS:
      When confounding factors are controlled, patient outcome is the same if
      ventilator-associated pneumonia has been diagnosed by protected specimen brush or
      by another sampling method.

PMID- 9039886
TI  - A 65-year-old man with an inguinal hernia.

PMID- 9039887
TI  - An 82-year-old woman with cataracts, 1 year later.

PMID- 9039888
TI  - Systems approaches and the delivery of health services.

PMID- 9039889
TI  - Protecting the health of children of immigrants. Innocent victims of adult
      policy.

PMID- 9039890
TI  - A model of empathic communication in the medical interview.
AB  - OBJECTIVE: To formulate an empirically derived model of empathic communication in
      medical interviews by describing the specific behaviors and patterns of
      interaction associated with verbal expressions of emotion. DESIGN: A descriptive,
      qualitative study of verbal exchanges using 11 transcripts and 12 videotapes of
      primary care office visits to a total of 21 physicians. SETTING: An urban health
      maintenence organization (HMO), an urban university-based general medicine
      clinic, and an urban community hospital general medicine clinic. ANALYTIC METHOD:
      Individual review of transcripts by each research team member to identify
      instances of expressed or implied emotional themes and to observe the physicians'
      responses. Individual ratings were compared in group discussions to achieve
      consensus about the classifications. Similar consensus-based classification was
      used for review of videotapes. RESULTS: We observed that patients seldom
      verbalize their emotions directly and spontaneously, tending to offer clues
      instead. If invited to elaborate, patients may then express the emotional concern
      directly, and the physician may respond with an accurate and explicit
      acknowledgment. In most of the interviews, the physicians allowed both clues and
      direct expressions of affect to pass without acknowledgment, returning instead to
      the preceding topic, usually the diagnostic exploration of symptoms. With
      emotional expression so terminated, some patients attempted to raise the topic
      again, sometimes repeatedly and with escalating intensity. We noted a parallel
      dynamic for encounters in which patients sought praise. We summarized the full
      interactional sequence in a simple descriptive model. CONCLUSIONS: This
      empirically derived model of empathic communication has practical implications
      for clinicians and students who want to improve their communication and
      relationship skills. Based on our observations, the basic empathic skills seem to
      be recognizing when emotions may be present but not directly expressed, inviting
      exploration of these unexpressed feelings, and effectively acknowledging these
      feelings so the patient feels understood. The frequent lack of acknowledgment by
      physicians of both direct and indirect expressions of affect poses a threat to
      the patient-physician relationship and warrants further study.

PMID- 9039891
TI  - Caught napping by clones.

PMID- 9039892
TI  - US decision 'will not limit gene patents'.

PMID- 9039893
TI  - Marijuana research gets backing at NIH.

PMID- 9039894
TI  - High-level ethics committee 'needed to guide genetics policy'.

PMID- 9039895
TI  - Cloning technique 'reveals legal loophole'.

PMID- 9039896
TI  - Abortion foe blamed for research head upset in Australia.

PMID- 9039897
TI  - Germany may relax animal experiment rules.

PMID- 9039898
TI  - Abbott sues Chiron over 'secrets' in heads of recruits.

PMID- 9039899
TI  - Culture clash tarnishes the image of star laboratory.

PMID- 9039900
TI  - Beyond the language barrier.

PMID- 9039901
TI  - Beyond the language barrier.

PMID- 9039902
TI  - Beyond the language barrier.

PMID- 9039903
TI  - Beyond the language barrier.

PMID- 9039904
TI  - The world's oldest spears.

PMID- 9039905
TI  - Nuclear transplantation. An udder way of making lambs.

PMID- 9039906
TI  - Phototransduction. Why lizards can't turn a blind eye.

PMID- 9039907
TI  - Amyloid fibrils. Mutations make enzyme polymerize.

PMID- 9039908
TI  - A pivotal Archaea group.

PMID- 9039909
TI  - Instability, unfolding and aggregation of human lysozyme variants underlying
      amyloid fibrillogenesis.
AB  - Tissue deposition of soluble proteins as amyloid fibrils underlies a range of
      fatal diseases. The two naturally occurring human lysozyme variants are both
      amyloidogenic, and are shown here to be unstable. They aggregate to form amyloid
      fibrils with transformation of the mainly helical native fold, observed in
      crystal structures, to the amyloid fibril cross-beta fold. Biophysical studies
      suggest that partly folded intermediates are involved in fibrillogenesis, and
      this may be relevant to amyloidosis generally.

PMID- 9039910
TI  - Lower Palaeolithic hunting spears from Germany.
AB  - Little is known about the organic component of Lower and Middle Palaeolithic
      technologies, particular with respect to wooden tools. Here I describe some
      wooden throwing spears about 400,000 years old that were discovered in 1995 at
      the Pleistocene site at Schoningen, Germany. They are thought to be the oldest
      complete hunting weapons so far discovered to have been used by humans. Found in
      association with stone tools and the butchered remains of more than ten horses,
      the spears strongly suggest that systematic hunting, involving foresight,
      planning and the use of appropriate technology, was part of the behavioural
      repertoire of pre-modern hominids. The use of sophisticated spears as early as
      the Middle Pleistocene may mean that many current theories on early human
      behaviour and culture must be revised.

PMID- 9039911
TI  - Viable offspring derived from fetal and adult mammalian cells.
AB  - Fertilization of mammalian eggs is followed by successive cell divisions and
      progressive differentiation, first into the early embryo and subsequently into
      all of the cell types that make up the adult animal. Transfer of a single nucleus
      at a specific stage of development, to an enucleated unfertilized egg, provided
      an opportunity to investigate whether cellular differentiation to that stage
      involved irreversible genetic modification. The first offspring to develop from a
      differentiated cell were born after nuclear transfer from an embryo-derived cell
      line that had been induced to become quiescent. Using the same procedure, we now
      report the birth of live lambs from three new cell populations established from
      adult mammary gland, fetus and embryo. The fact that a lamb was derived from an
      adult cell confirms that differentiation of that cell did not involve the
      irreversible modification of genetic material required for development to term.
      The birth of lambs from differentiated fetal and adult cells also reinforces
      previous speculation that by inducing donor cells to become quiescent it will be
      possible to obtain normal development from a wide variety of differentiated
      cells.

PMID- 9039912
TI  - Evidence against a dedicated system for word learning in children.
AB  - Children can learn aspects of the meaning of a new word on the basis of only a
      few incidental exposures and can retain this knowledge for a long period-a
      process dubbed 'fast mapping". It is often maintained that fast mapping is the
      result of a dedicated language mechanism, but it is possible that this same
      capacity might apply in domains other than language learning. Here we present two
      experiments in which three- and four-year-old children and adults were taught a
      novel name and a novel fact about an object, and were tested on their retention
      immediately, after a 1-week delay or after a 1-month delay. Our findings show
      that fast mapping is not limited to word learning, suggesting that the capacity
      to learn and retain new words is the result of learning and memory abilities that
      are not specific to language.

PMID- 9039913
TI  - A cGMP-gated cation channel in depolarizing photoreceptors of the lizard parietal
      eye.
AB  - Rods and cones of the two vertebrate lateral eyes hyperpolarize when illuminated,
      a response generated by a cyclic GMP cascade leading to cGMP hydrolysis and
      consequently the closure of cGMP-gated, non-selective cation channels that are
      open in darkness. Lizards and other lower vertebrates also have a parietal
      (third) eye, which contains ciliary photoreceptors that under dark-adapted
      conditions depolarize to light instead. Depolarizing light responses are
      characteristic of most invertebrate rhabdomeric photoreceptors, and are thought
      to involve a phosphoinositide signalling pathway (see, for example, refs 7-9).
      Surprisingly, we have found in excised membrane patches a cGMP-gated channel that
      is selectively present at high density on the outer segment (the presumptive
      light-sensitive part) of the parietal eye photoreceptor. Like the light-activated
      channel of the cell, it is non-selective among cations. Inositol trisphosphate
      (InsP3) had no effect on the same membrane patches. These findings suggest that
      the photoreceptors of the parietal eye, like rods and cones, use a cGMP cascade
      and not an InsP3-mediated pathway for phototransduction, but in this case light
      increases cGMP. A unifying principle of evolutionary significance emerges: that
      phototransductions in various ciliary photoreceptors, whether hyperpolarizing or
      depolarizing, uniformly use a cGMP cascade and a cGMP-gated channel to generate
      the light response, although there are rich variations in the details.

PMID- 9039914
TI  - Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor
      subunit.
AB  - A common feature of general anaesthetic agents is their ability to potentiate
      neuronal inhibition through GABA(A) (gamma-aminobutyric acid) receptors. At
      concentrations relevant to clinical anaesthesia, these agents cause a dramatic
      stimulation of the chloride currents that are evoked by the binding of the
      natural ligand, GABA. Although there is widespread evidence that the sensitivity
      of GABA(A) receptors to anaesthetic agents is heterogeneous, the structural basis
      of these differences is largely unknown. Variations in subunit composition can
      have profound effects on the sensitivity of GABA(A) receptors to modulatory
      agents such as benzodiazepines. However, strict subunit specificity has not been
      demonstrated for the potentiating effects of anaesthetic agents. Here we describe
      a new class of human GABA(A) receptor subunit (epsilon) that can assemble with
      alpha- and beta-subunits and confer an insensitivity to the potentiating effects
      of intravenous anaesthetic agents. The epsilon-subunit also abolishes the normal
      outward rectification of recombinant receptors in which it assembles. The
      expression pattern of this subunit in the brain suggests a new target for
      manipulation of neuronal pathways within the basal ganglia.

PMID- 9039915
TI  - Mechanism of resistance of African trypanosomes to cytotoxic human HDL.
AB  - Trypanosoma brucei brucei, the causative agent of ngana in cattle, is non
      infectious to humans because of its sensitivity to the cytolytic activity of
      normal human serum. The toxin in normal human serum is human haptoglobin-related
      protein (Hpr) which is found either as an apolipoprotein associated with a minor
      subclass of high-density lipoprotein (HDL), named trypanosome lytic factor
      (TLF1), or as an unstable, high-molecular-mass protein complex known as TLF2
      (refs 5, 9-12). TLF-mediated lysis of T. b. brucei requires binding,
      internalization and lysosomal targeting. The human sleeping-sickness trypanosome,
      Trypanosoma brucei rhodesiense is resistant to TLF. Our studies reveal that
      resistant trypanosomes fail to endocytose TLF yet continue to bind TLF through
      cell-surface receptors. On the basis of these results, we conclude that one
      mechanism of resistance of human sleeping-sickness trypanosomes to human serum is
      decreased internalization of receptor-bound TLF.

PMID- 9039916
TI  - Hrs-2 is an ATPase implicated in calcium-regulated secretion.
AB  - Associations between proteins present on neurotransmitter-containing vesicles and
      on the presynaptic membrane are thought to underlie docking and fusion of
      synaptic vesicles with the plasma membrane, which are obligate steps in regulated
      neurotransmission. SNAP-25 resides on the plasma membrane and interacts with
      syntaxin (a plasma membrane t-SNARE) and VAMP (a vesicle v-SNARE) to form a core
      protein complex thought to be an intermediate in a biochemical pathway that is
      essential for vesicular transport. We have now characterized a protein, Hrs-2,
      that interacts with SNAP-25. The binding of Hrs-2 to SNAP-25 is inhibited by
      calcium in the physiological concentration range that supports synaptic
      transmission. Furthermore, Hrs-2 binds and hydrolyses nucleoside triphosphates
      with kinetics that suggest that ATP is the physiological substrate for this
      enzyme. Hrs-2 is expressed throughout the brain and is present in nerve
      terminals. Moreover, recombinant Hrs-2 inhibits calcium-triggered 3H
      noradrenaline release from permeabilized PC12 cells. Our results suggest a role
      for Hrs-2 in regulating secretory processes through calcium- and nucleotide
      dependent modulation of vesicle-trafficking protein complexes.

PMID- 9039917
TI  - pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce
      the Wingless signal in Drosophila.
AB  - Members of the Wnt/Wingless (Wg) family of signalling proteins organize many
      aspects of animal development by regulating the expression of particular target
      genes in responding cells. Recent biochemical studies indicate that the
      vertebrate HMG-domain proteins Lef-1 and XTcf-3 can physically interact with beta
      catenin, a homologue of Drosophila Armadillo (Arm), the most downstream component
      known in the Wnt signal transduction pathway. However, these studies do not
      address whether the endogenous Lef/Tcf family members are required in vivo to
      transduce Wnt signals. Using genetic methods in Drosophila, we define a new
      segment polarity gene, pangolin (pan), and show that its product is required in
      vivo for Wg signal transduction in embryos and in developing adult tissues. In
      addition, we show that pan encodes a Lef/Tcf homologue and provide evidence that
      its protein product binds to the beta-catenin homologue Armadillo in vivo.
      Finally, we demonstrate that Pan functions downstream of Arm to transduce the Wg
      signal. Thus, our results indicate that Pan is an essential component of the Wg
      transduction pathway and suggest that it acts directly to regulate gene
      transcription in response to Wg signalling.

PMID- 9039918
TI  - Crystal structure of the anthrax toxin protective antigen.
AB  - Protective antigen (PA) is the central component of the three-part protein toxin
      secreted by Bacillus anthracis, the organism responsible for anthrax. After
      proteolytic activation on the host cell surface, PA forms a membrane-inserting
      heptamer that translocates the toxic enzymes, oedema factor and lethal factor,
      into the cytosol. PA, which has a relative molecular mass of 83,000 (M(r) 83K),
      can also translocate heterologous proteins, and is being evaluated for use as a
      general protein delivery system. Here we report the crystal structure of
      monomeric PA at 2.1 A resolution and the water-soluble heptamer at 4.5 A
      resolution. The monomer is organized mainly into antiparallel beta-sheets and has
      four domains: an amino-terminal domain (domain 1) containing two calcium ions and
      the cleavage site for activating proteases; a heptamerization domain (domain 2)
      containing a large flexible loop implicated in membrane insertion; a small domain
      of unknown function (domain 3); and a carboxy-terminal receptor-binding domain
      (domain 4). Removal of a 20K amino-terminal fragment from domain 1 allows the
      assembly of the heptamer, a ring-shaped structure with a negatively charged
      lumen, and exposes a large hydrophobic surface for binding the toxic enzymes. We
      propose a model of pH-dependent membrane insertion involving the formation of a
      porin-like, membrane-spanning beta-barrel.

PMID- 9039919
TI  - Hyperlipidemia in solid organ transplantation.

PMID- 9039920
TI  - Treatment of hyperlipidemia in renal transplant recipients.

PMID- 9039921
TI  - GB hepatitis agent in cadaver organ donors and their recipients.
AB  - BACKGROUND: The cloning of yet another hepatitis virus, GB virus-C (GBV-C), has
      provided the opportunity to study the prevalence, and clinical and laboratory
      characteristics, associated with GBV-C infection among cadaver organ donors and
      recipients of organs from infected donors. METHODS: Stored sera from a cohort of
      cadaver organ donors from eight organ procurement organizations, representing
      different geographic regions of the United States previously screened for
      hepatitis C virus (HCV) infection, were tested for GBV-C RNA by polymerase chain
      reaction using degenerate primers derived from the NS3 helicase and 5'
      untranslated regions of the GBV-C genome. Pre- and posttransplantation clinical
      data, and prevalence of GBV-C RNA among recipients of organs from GBV-C RNA
      positive and -negative donors, were studied at one of the organ procurement
      organizations. RESULTS: Twenty-one of 76 (27.6%) anti-HCV ELISA1-positive donors
      tested positive for GBV-C RNA compared with 6 of 82 (7.3%) ELISA1-negative donors
      (P=0.001). The prevalence of GBV-C RNA, extrapolated to all cadaver organ donors,
      was 8.3% (95% confidence interval [CI]: 5.6-11.1%) and was higher than the
      prevalence of HCV RNA (2.4%). Among ELISA1-positive donors, GBV-C RNA was present
      in 13 of 35 (37%) donors with HCV RNA, compared with 8 of 41 (20%) donors without
      HCV RNA (odds ratio [OR]=2.44, P=0.09). Blood alcohol level of more than 100
      mg/dl (OR=9.43, P=0.05) and a positive anti-HCV ELISA2 (OR=4.58, P=0.001) were
      significantly associated with GBV-C infection. In addition, there was a trend
      toward an association between history of drug abuse (OR=5.23, P=0.06) and younger
      age (OR=0.97/year, P=0.06) with GBV-C infection. Organs from four GBVC-positive
      donors and 47 GBV-C-negative donors procured by the New England Organ Bank
      (Newton, MA) were transplanted into 6 and 79 recipients, respectively. Among
      recipients of organs from GBV-C RNA. positive donors, the posttransplantation
      prevalence of GBV-C RNA (25%) was not significantly higher than among recipients
      of organs from GBV-C RNA-negative donors (23%). Among recipients in whom both pre
      and posttransplantation sera were available, one of three (33%) recipients of
      kidneys from GBV-C RNA-positive donors acquired GBV-C RNA after transplantation,
      compared with 4 of 40 (10%) recipients of kidneys from GBV-C RNA-negative donors.
      After a median follow up of 6 years, the posttransplantation prevalence of liver
      disease, and graft and patient survival, were not significantly different between
      recipients of organs from GBV-C RNA-positive and -negative donors. CONCLUSIONS:
      Although GBV-C could be transmitted by organ transplantation, the results of this
      study preclude definitive conclusions. Further studies are required to determine
      the risk of transmission of GBV-C by organ transplantation and its role in
      posttransplantation liver disease.

PMID- 9039922
TI  - Simultaneous pancreas and kidney transplant rejection: separate or synchronous
      events?
AB  - The results of simultaneous pancreas and kidney transplantation (SPK) cannot be
      matched by pancreas transplantation alone (PTA), in part because an independent
      diagnosis of pancreas graft rejection remains difficult. The relationship between
      rejection of the pancreas and rejection of the kidney is poorly understood, and
      it is not known whether simultaneous transplantation of both organs confers true
      protection to either graft. To study these questions, reliable canine
      allotransplant models of kidney transplantation alone (KTA), PTA, and SPK were
      established. Sixty-seven mongrel dogs received KTA (n=21), PTA (n=23), or SPK
      (n=23) with either no immunosuppression, low-dose cyclosporine (CsA)-based
      immunosuppression, or high-dose CsA-based immunosuppression. Needle core biopsy
      (NCB) and fine needle aspiration biopsy (FNAB) were performed at 0, 2, 4, 7, 9,
      11, 14, 21, and 30 days or at the time of graft failure. Pancreas and kidney
      graft survival after SPK was significantly shorter in dogs given low-dose CsA
      than in dogs given high-dose CsA (pancreas, P<0.04; kidney, P<0.03). Concurrent
      NCBs and FNABs were performed on 227 occasions in pancreas grafts and 229
      occasions in kidney grafts. The time to initial evidence of rejection by NCB was
      not different in any immunosuppressed group. Synchronous rejection occurred in
      73% of immunosuppressed SPK biopsies. Kidney-only rejection occurred in 23% of
      biopsies and pancreas-only rejection occurred in only 3% after SPK. All markers
      of pancreas graft rejection were poor, with the most sensitive being NCB of the
      simultaneously transplanted kidney. In summary, recipients of SPK required more
      immunosuppression than recipients of PTA, and improved PTA survival should be
      achievable with more sensitive markers of rejection. Markers of kidney rejection
      were the most sensitive indicators of pancreas rejection, and independent
      pancreas rejection was uncommon after SPK.

PMID- 9039924
TI  - Reduction of proteolysis by venous-systemic oxygen persufflation during rat liver
      preservation and improved functional outcome after transplantation.
AB  - An increase of cytosolic proteolytic activity during ischemic preservation and
      consecutive tissue degradation have recently been recognized as a major
      pathogenetic factor for liver injury during ischemia/reperfusion. In the present
      study, we propose a method for preventing proteolytic tissue disintegration,
      which results in improved recovery of the liver after transplantation. Livers
      were harvested from rats and stored for 24 hr at 4 degrees C in University of
      Wisconsin solution (group A). Others were additionally persufflated with gaseous
      oxygen via the inferior caval vein during this time (group B). At the end of
      ischemic preservation, proteolysis was confirmed in group A, with significantly
      elevated tissue levels of free alanine and free amino groups, whereas proteolysis
      was prevented in group B. After transplantation, the integrity of the graft was
      significantly improved in group B, in which there was a 50% reduction of plasma
      activities of alanine amino-transferase and a twofold increase in hepatic bile
      production after the onset of reperfusion, as compared with group A. Moreover,
      venous-systemic oxygen persufflation during cold preservation significantly
      attenuated the rise in plasma levels of malondialdehyde (MDA) after liver
      transplantation. In conclusion, venous-systemic oxygen persufflation during
      ischemic storage prevents tissue proteolysis and reduces parenchymal injury after
      transplantation in vivo; this technique may, thus, represent a useful adjunct in
      long-term liver preservation with University of Wisconsin solution.

PMID- 9039923
TI  - Superiority of sirolimus (rapamycin) over cyclosporine in augmenting allograft
      and xenograft survival in mice treated with antilymphocyte serum and donor
      specific bone marrow.
AB  - BACKGROUND: Sirolimus is a potent immunosuppressive agent with great therapeutic
      potential. The objective of our study was to evaluate the efficacy of sirolimus
      versus cyclosporine in augmenting the unresponsiveness induced by an
      antilymphocyte serum (ALS)/donor-specific bone marrow (BM)-based regimen across
      three levels of histoincompatibility: class I and II disparate (DBA/2 to B6AF1),
      complete mismatch (AKR to C57BL/6), and xenograft (ACI rat to B6AF1). METHODS:
      Full-thickness skin grafts were taken from donors and placed on recipients in
      standard fashion. Seven groups of recipient mice (n=10-28) received various
      combinations of the following treatment protocols: sirolimus, 1.5 mg/kg (3.0
      mg/kg for xenografts) every other day from day 0 to day 12; cyclosporine, 50
      mg/kg every other day from day 10 through 22; ALS, 0.5 ml on days -1 and 2 for
      allografts and days -1, 2, and 4 for xenografts; and BM, 25 million donor
      specific cells IV on day 7. RESULTS: The administration of ALS or ALS/BM resulted
      in modest but significant prolongation of skin graft survival in all combinations
      tested. Cyclosporine combined with ALS or ALS/BM significantly extended allograft
      survival compared with ALS or ALS/BM alone (P<0.05) but had no effect on
      xenograft survival. In contrast, the combination of sirolimus with ALS or ALS/BM
      resulted in a two- to threefold increase in allograft survival and over a
      fourfold increase in xenograft survival when compared with the comparable
      cyclosporine-based regimen. Additionally, lymphocytes isolated from class I and
      II incompatible mice with skin grafts surviving >100 days demonstrated markedly
      reduced interleukin 2 and interferon-gamma secretion in response to irradiated
      donor-specific lymphocytes in culture. CONCLUSIONS: In the regimens tested,
      sirolimus was superior to cyclosporine in augmenting donor BM-induced skin graft
      prolongation in ALS-treated mice across all levels of histoincompatibility.

PMID- 9039925
TI  - Hepatic allograft procurement from non-heart-beating donors: limits of warm
      ischemia in porcine liver transplantation.
AB  - To investigate the tolerance to warm ischemia of liver grafts from non-heart
      beating donors, porcine orthotopic liver transplantation was performed using
      grafts obtained at various periods after cardiac arrest. Graft viability was
      investigated in relation to changes in hepatic adenine nucleotide metabolism. In
      donors, livers were divided into four groups according to warm ischemic time
      after cardiac arrest (group 1: 0 min, n=3; group 2: 30 min, n=3; group 3: 60 min,
      n=5; group 4: 90 min, n=4). Thereafter, the livers were flushed and preserved for
      4 hr using 4 degrees C Euro-Collins solution. After surgery, all of the
      recipients in groups 1, 2, and 3 survived more than 4 days, except for one pig in
      group 3 that died of bleeding from an arterial catheter on day 2. By contrast,
      all of the recipients in group 4 died within 12 hr. The serum glutamic
      oxaloacetic transaminase concentration at 4 hr after reperfusion of the graft was
      significantly higher in group 4 (mean+/-SE, 2563+/-556 IU/L) than in groups 1, 2,
      and 3 (298+/-29 IU/L, 1226+/-222 IU/L, and 1181+/-174 IU/L, respectively). The
      adenylate energy charge of the liver graft recovered at 1 hr after reperfusion of
      the graft to 0.852+/-0.013, 0.845+/-0.003, and 0.842+/-0.003 in groups 1, 2, and
      3, respectively. The recovery was significantly suppressed in group 4 (0.796+/
      0.011). The hepatic adenosine triphosphate concentration also was significantly
      lower in group 4 compared with the other groups. The present study suggests that
      liver allografts can be used from non-heart-beating donors subjected to warm
      ischemia for less than 60 min. Postoperative survival is associated with prompt
      recovery of the adenylate energy charge of the liver graft.

PMID- 9039926
TI  - Patterns of graft infiltration and cytokine gene expression during the first 10
      days of kidney transplantation.
AB  - Understanding of the events preceding acute cellular rejection of kidney
      transplants would be useful in the development of immunosuppressive strategies to
      prevent rejection. Information about these events in humans has been scarce,
      because of the lack of early, serial, biopsy samples. We took daily fine needle
      aspirates from kidney allografts for the first 10 days after transplant. Samples
      were analyzed by morphological cytology of graft-infiltrating cells, and reverse
      transcriptase-polymerase chain reaction for detection of interleukin (IL)-2, IL
      4, IL-6, IL-10, and gamma-interferon gene expression. During the first 4 days,
      all of the grafts developed a low-grade monocyte-rich mononuclear cell
      infiltrate, accompanied by IL-10 gene expression. Thereafter, the infiltrates
      either remained stable or intensified. Of the 13 grafts with dense infiltrates,
      seven developed graft dysfunction. The remaining six did not, despite significant
      interstitial infiltrates. Both rejecting and nonrejecting dense infiltrates were
      associated with a biphasic pattern of IL-2 and gamma-interferon gene expression,
      preceding and accompanying lymphocytic graft infiltration. Grafts that did not
      develop dense infiltrates had no detectable IL-2 or gamma-interferon gene
      expression and did not suffer cellular rejection during the study period. The
      development of both rejecting and nonrejecting infiltrates was strongly
      associated with DR mismatches between donor and recipient. IL-2 and gamma
      interferon gene expression are necessary, but not sufficient, for the development
      of acute cellular rejection in the first 10 days of kidney transplantation, and
      are more closely associated with the period leading up to rejection than with the
      period of graft dysfunction.

PMID- 9039927
TI  - Effects of three immunosuppressive regimens on vertebral bone density in renal
      transplant recipients: a prospective study.
AB  - The influence of three different immunosuppressive regimens with cyclosporine
      (CsA) on the development of osteopenia in renal transplant patients was assessed.
      Fifty-three adults with first kidney transplants participated in a randomized
      trial to analyze the efficacy of three different immunosuppressive regimens: CsA
      alone (group 1), CsA plus steroids (group 2), and CsA plus steroids plus
      azathioprine (group 3). Lumbar spine bone mineral density was assessed by dual
      energy x-ray absorptiometry every 6 months for 18 months. The values for
      trabecular mass were expressed as bone mineral density and as a fraction of the
      standard deviation of the mean of the normal value for patient's sex and decade
      of age (Z-score). Statistical analysis was performed on Z-score and "Z-score
      change" (value after 6 months minus the basal value at transplantation). At the
      18th month, the Z-score increased significantly in treatment group 1 without
      steroids (P=0.006) and decreased significantly in steroid-treated groups 2
      (P<0.001) and 3 (P<0.001). Comparing the two genders, Z-score decreased less in
      premenopausal women than in men (P=0.018). "Z-score change" did not correlate
      with steroid dosage, was high in patients with high basal bone mineral density,
      and was directly associated with the duration of dialysis (P=0.008). In
      conclusion, premenopausal transplant recipients showed a lower decrease of lumbar
      bone mineral density than men. In transplant recipients given CsA with steroids,
      lumbar bone mineral density decreased significantly, while it increased
      significantly in patients given CsA alone.

PMID- 9039928
TI  - Maintenance therapy with triple versus double immunosuppressive regimen in renal
      transplantation: a meta-analysis.
AB  - BACKGROUND: The purpose of this study was to compare the effect of triple
      immunosuppressive maintenance therapy (cyclosporine, azathioprine, and
      prednisolone) with that of double therapy (cyclosporine and prednisolone) in
      renal transplant patients using graft failure, mortality, and acute rejection
      episodes as outcome measures. METHODS: A systematic overview of articles
      published between 1984 and 1995 was done. MEDLINE, Science Citation Index,
      reference lists, and expert files were searched. Of 449 originally identified
      studies, five controlled trials were finally selected. Information was retrieved
      on the topics of methodological quality, baseline characteristics, interventions,
      and outcomes. The Mantel-Haenszel fixed effect method was used to combine results
      from different studies. RESULTS: Pooled analysis did not show a statistically
      significant difference between triple-drug therapy and double-drug therapy in the
      main outcome of graft failure (odds ratio [OR], 0.82; 95% confidence interval
      [CI], 0.61-1.16), survival (OR, 0.83; 95% CI, 0.57-1.21), or the occurrence of
      acute graft rejection (OR, 1.02; 95% CI, 0.76-1.36). There was a nonsignificant
      trend for better graft survival under triple therapy. A lower withdrawal rate
      suggests a more stable immunosuppressive effect on triple therapy. CONCLUSIONS:
      There is no statistically significant difference in the long-term management of
      renal transplant recipients between the two treatment regimens.

PMID- 9039929
TI  - Beneficial effect of lamivudine in recurrent hepatitis B after liver
      transplantation.
AB  - Orthotopic liver transplantation (OLT) in patients infected with hepatitis B
      virus (HBV) is known to be associated with a high recurrence rate and poor
      prognosis. Interferon treatment in these patients offers little benefit and may
      lead to further complications. Lamivudine, the (-)enantiomer of 3'-thiacytidine,
      a 2'3'-dideoxynucleoside, is known to be a potent inhibitor of HBV replication in
      patients with chronic HBV infection. Three HBV-positive OLT patients were
      administrated lamivudine, 100 mg x 1 orally, for a period of at least 20 weeks,
      in an open, compassionate-use basis. All three patients were HBV DNA-negative
      before OLT. HBV reinfection occurred at a median time of 7 months (range, 6-9
      months) after OLT, in spite of adequate immunoprophylaxis. All three patients had
      high serum transaminase levels (alanine aminotransferase [ALT], 103-324 U/L) and
      histologic evidence of recurrent HBV infection of the grafted liver, and HBV DNA
      was evident in the sera of all of them. Six weeks after lamivudine treatment, HBV
      DNA disappeared from the serum of all patients (detected by hybridization); by
      the 10th week, HBV DNA was also negative by polymerase chain reaction in two out
      of three patients. Interestingly, the one patient who was HBV DNA positive by
      polymerase chain reaction still has mildly elevated ALT levels, whereas the other
      two patients have normal ALT levels. We also noted that on the 5th week there was
      a transient elevation of serum ALT levels in two patients. No adverse effects or
      rejection episodes were noted. In conclusion, lamivudine is a beneficial and well
      tolerated therapy in OLT patients with recurrent HBV infection. We are studying
      the effect of lamivudine in other patients and for a longer period of time.

PMID- 9039930
TI  - Randomized controlled trial to evaluate flush and reperfusion techniques in liver
      transplantation.
AB  - To determine the impact of different flush and reperfusion techniques on
      postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants
      were randomly assigned into four groups as follows: group 1 (n=31), portal vein
      flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena
      caval venting; group 3 (n=29), portal vein flush with vena caval venting; and
      group 4 (n=19), hepatic artery flush with vena caval venting. Donor and recipient
      characteristics were similar. Extensive intraoperative and postoperative
      monitoring was performed and measurements were documented immediately before
      reperfusion and at 1, 5, 15, and 30 min after reperfusion. PRS was defined by
      three criteria: mean arterial pressure (MAP) <60 mmHg at 1 min after reperfusion,
      MAP <60 mmHg at 5 min after reperfusion, and a decrease of 30% or more for the
      MAP percent area under the curve during the initial 5 min after reperfusion
      (%AUC). Using these definitions, the overall incidence of PRS was 21%, 8%, and
      43%, respectively. Group 1 was the most hemodynamically stable; the incidence of
      PRS in group 1 was 2/31 (7%) at 1 min and 8/31 (25%) using %AUC criteria compared
      with 7/21 (33%) at 1 min and 12/21 (57%) using %AUC criteria for group 2
      (P<0.05). The patients in groups 3 and 4 (vena caval venting) demonstrated
      smaller percentage increases in serum potassium levels (as determined by %AUC;
      4.3+/-6.8 and 0.3+/-5.4, vs. 15.1+/-8.1 for group 1 and 22.9+/-8.2 for group 2).
      The difference between group 4 and group 2 was statistically significant
      (P<0.05). The increases in serum potassium did not translate into increased
      cardiac or hemodynamic instability. Combining all data obtained over the first 30
      min after reperfusion, there was no statistically significant difference in
      hemodynamic or biochemical changes noted among the four groups. Postoperative
      liver function was similar among the four groups. We conclude that portal vein
      flush without vena caval venting provided a lower incidence of PRS than any other
      technique. Vena caval venting decreased the release of potassium into the
      circulation. Postoperative graft function was not significantly affected by flush
      and reperfusion techniques.

PMID- 9039931
TI  - Influence of cyclic guanosine monophosphate changes on hemodynamics after
      reperfusion in liver transplantation.
AB  - Orthotopic liver transplantation (OLT) is often associated with hemodynamic
      instability upon reperfusion, recognized as postreperfusion syndrome. Changes in
      vascular tone due to humoral factors released upon reperfusion of the graft have
      been suggested as a possible mechanism. In this study, we looked at the
      perioperative changes in cyclic guanosine monophosphate (cGMP), a mediator of
      vascular smooth muscle relaxation, and investigated its relationship with
      hemodynamic parameters. cGMP was measured in the plasma of 14 patients undergoing
      OLT by radioimmunoassay serially at the preanhepatic and anhepatic phases, and
      after reperfusion at 30, 60, and 120 min. Hemodynamic data recorded were systemic
      and pulmonary arterial pressures, cardiac output, and pulmonary and systemic
      vascular resistance. cGMP decreased markedly after reperfusion from a baseline
      level of 5.33+/-0.7 ng/ml to 1.63+/-0.5 ng/ml (P<0.01). Pulmonary arterial
      pressure increased from 17+/-1.21 mmHg to 23.5+/-1.9 mmHg (P<0.05), and pulmonary
      vascular resistance increased from 62.8 +/-12.9 dynes/sec/cm5 to 135+/-42.7
      dynes/sec/cm5 (P<0.01). Changes in cardiac output and systemic vascular
      resistance were not significant. The changes in cGMP correlated with pulmonary
      arterial pressure (r=0.74, P=0.005) and pulmonary vascular resistance (r=0.7,
      P=0.01). These data confirm the occurrence of hemodynamic changes during OLT, and
      provide evidence to suggest that the reduction in cGMP after reperfusion may
      mediate the vascular changes.

PMID- 9039932
TI  - Effects of hypoxemia on early postoperative course of liver transplantation in
      pediatric patients with intrapulmonary shunting.
AB  - Nine pediatric patients (mean age, 10 years) with biliary atresia, who had
      hypoxemia related to intrapulmonary shunting, underwent living related liver
      transplantation. The effects of hypoxemia during the early postoperative period
      after liver transplantation on cardiopulmonary and renal function, as well as on
      transplanted liver, were analyzed. Based on the degree of shunt ratio calculated
      by technetium-99m macroaggregated albumin scintigraphy, the nine patients were
      included in the moderate group (shunt ratio under 40%, n=4) or the severe group
      (shunt ratio over 40%, n=5). Partial pressure of arterial oxygen was maintained
      at normal range in the moderate group, while that in the severe group
      persistently had very low values (<50 mmHg), in spite of a high degree of oxygen
      supply. However, all patients in the severe group maintained stable
      cardiopulmonary vital signs, including systemic blood pressure, heart rate,
      respiratory rate, and cardiac index. They also demonstrated stable renal
      function. None of the patients died of cardiopulmonary or renal insufficiency
      after transplantation, but three patients died of portal vein thrombosis, sepsis,
      and intracranial hemorrhage (one each). The minimal adverse effect of hypoxemia
      on the transplanted liver was confirmed by a rapid increase of arterial ketone
      body ratio, low peak values (under 200 IU/L) of aspartate aminotransferase, and a
      steady decrease of serum total bilirubin. Four patients encountered surgical
      complications, including two bile leaks from the cut liver surface, two leaks
      from bilioenteric anastomosis, and one intestinal perforation. Six patients
      suffered from bacterial infections, including four wound infections, three right
      subphrenic abscesses, one cholangitis, and two systemic sepses. All patients in
      the moderate group recovered from hypoxemia, but four of five patients in the
      severe group have not recovered during the follow-up period between 4 and 9
      months. It was concluded that the adverse effects of hypoxemia on cardiopulmonary
      and renal function and transplanted liver were minimal, so that patients with
      severe hypoxemia could tolerate the stress of liver transplantation without
      special management. However, the high incidence of surgical complication and
      infection suggested the adverse effects of hypoxemia on wound healing and
      resistance to bacteria infection.

PMID- 9039933
TI  - Monocyte chemotactic peptide-1 expression and monocyte infiltration in acute
      renal transplant rejection.
AB  - Mononuclear cell infiltration is a common histopathological feature of acute
      renal transplant rejection, in which it seems to play a key role in the
      pathogenesis of tubulointerstitial lesions. Monocyte chemotactic peptide-1 (MCP
      1) is a specific chemotactic and activating factor for monocytes. Thus, the
      present study was aimed at evaluating MCP-1 gene and protein expression in renal
      biopsies of kidney transplant recipients with acute deterioration of graft
      function, and to correlate it with the extent of monocyte infiltration. We
      studied 20 kidney transplant recipients with acute graft dysfunction (13 with
      acute rejection, seven with acute tubular damage). MCP-1 gene and protein
      expression were analyzed by in situ hybridization and immunohistochemistry,
      respectively. CD68-positive cells were identified as monocytes. CD68-positive
      cell number and MCP-1 expression were quantified by a computerized image analysis
      system. MCP-1 gene expression, undetectable in normal human kidneys, was
      strikingly increased in patients with acute rejection. The chemokine localized
      mainly to the proximal tubular cells and to mononuclear-infiltrating cells. In
      patients with acute tubular damage, the MCP-1 expression, even if higher than in
      controls, was significantly lower than in acute rejection. The expression of the
      chemokine strictly correlated with the number of infiltrating monocytes (r=0.87,
      P<0.05). Moreover, we measured MCP-1 urinary excretion by ELISA, in eight normal
      subjects (36+/-16 pg/mg urine creatinine), in 13 clinically stable transplant
      recipients (33+/-9 pg/mg, ns vs. normal patients), in 12 transplant recipients
      with acute rejection (250+/-46 pg/mg, P<0.01 vs. normal patients), and in five
      transplant recipients with acute tubular damage (97+/-33 pg/mg, P<0.05 vs.
      controls and patients with acute rejection). Urinary MCP-1 excretion directly
      correlated with renal MCP-1 gene expression (r=0.65, P=0.05). Finally, we
      observed a significant reduction in MCP-1 urine levels in patients with acute
      rejection, who responded to the antirejection treatment. In conclusion, our data
      suggest that MCP-1 may play a critical role in modulating monocyte influx and
      consequent tubulointerstitial damage in acute rejection. Therefore, an increase
      in urinary MCP-1 excretion may represent an early signal of ongoing acute graft
      rejection.

PMID- 9039934
TI  - Human monocytes activate porcine endothelial cells, resulting in increased E
      selectin, interleukin-8, monocyte chemotactic protein-1, and plasminogen
      activator inhibitor-type-1 expression.
AB  - Monocytes (Mo) are thought to be important effector cells in early xenograft
      rejection. Effects of Mo-endothelial cell (EC) interactions on EC activation in
      vitro were studied by coculturing human Mo or human monocytoid cell lines, U937
      and THP-1, with porcine EC. Without preactivation, U937 cells and Mo induced mRNA
      for the EC-specific adhesion receptor, E-selectin, expressed only on activated
      cells, after 2 hr. Surface protein was maximal when equal numbers of EC and Mo
      were cocultured. Increased mRNA expression of the chemokines, interleukin-8 and
      monocyte chemotactic protein-1, and the antifibrinolytic protein plasminogen
      activator inhibitor type-1, confirmed EC activation. Like E-selectin, plasminogen
      activator inhibitor type-1 mRNA was rapidly induced and returned to baseline
      after 24 hr, whereas chemokine gene expression was slower and more prolonged.
      Interleukin-1 receptor antagonist failed to modulate induction of E-selectin.
      Soluble tumor necrosis factor (TNF) alpha receptor inhibited E-selectin induced
      by TNF alpha, but not by U937 cells, and mRNA and protein on EC in Mo-EC mixtures
      cocultured at 1:1 ratios were not significantly reduced. The TNF alpha inhibitor
      did reduce E-selectin expression (30-40%), as well as induced chemokine gene
      expression (80%), at higher Mo-EC ratios. Despite this, minimal TNF alpha was
      detectable in supernatants. These results, along with the transwell experiments
      that confirmed a requirement for Mo-EC contact, suggest that membrane-bound TNF
      alpha may be involved. Thus, Mo-EC interactions in the porcine to human
      combination activated several EC functions, suggesting that initial Mo contact
      with the vessel wall of a xenogeneic graft may promote leukocyte recruitment,
      inflammation, and maintenance of thrombus, resulting in eventual organ
      destruction.

PMID- 9039935
TI  - Adoptive immunotherapy in canine chimeras.
AB  - Chimerism and tolerance after bone marrow transplantation provide excellent
      conditions for adoptive immunotherapy with T cells of the marrow donor. We
      studied adoptive immunotherapy in dog leukocyte antigen-identical canine
      littermate chimeras. Mixed chimeras were produced by conditioning treatment with
      total body irradiation of a dose of 10 Gy, a uniformly lethal dose in dogs, and
      infusion of between 1 x 10(8) and 2 x 10(8)/kg mononuclear marrow cells treated
      with absorbed antithymocyte globulin for inactivation of T cells. Donors were of
      opposite sex. Persistent mixed chimerism was induced in six of nine dogs,
      chimerism was complete in one dog, and only transient in two dogs. Tolerance to
      donor skin grafts was demonstrated in eight dogs, including a dog without
      cytogenetic evidence of chimerism. Lymphocytes of the marrow donor (between 3.2 x
      10(8)/kg and 4.1 x 10(8)/kg) were transfused at various times after
      transplantation. Nontransfused dogs survived without graft-versus-host disease
      (GVHD), whereas dogs transfused on days 1 and 2 and dogs transfused on days 21
      and 22 developed GVHD and died. In contrast, dogs transfused on days 61 and 62 or
      later survived without GVHD. Chimerism converted from mixed to complete in six of
      six transfused dogs and in one of eight nontransfused dogs (P<0.005). Donor
      lymphocyte transfusions 2 years and 4.5 years after transplantation induced split
      chimerism with lymphoid cells of donor origin and myeloid cells of host origin in
      one dog and complete chimerism in the other dog. Before lymphocyte collection,
      donors were immunized against tetanus toxin. Seven days after lymphocyte
      transfusion, recipients were given booster injections of tetanus toxoid and
      primary immunization against diphtheria toxin. In transfused animals, antibody
      titers against tetanus were demonstrated already before the booster injection.
      Transfused animals developed higher titers of antibody against tetanus and
      diphtheria toxin than nontransfused animals. Donor lymphocytes converted mixed
      chimerism into complete chimerism without producing GVHD, when the transfusion
      was delayed for 2 months or later after transplantation. Transfusion of donor
      lymphocytes transferred immune reactivity against tetanus toxin and improved
      reactivity against diphtheria toxin as a new antigen.

PMID- 9039936
TI  - Vascular endothelial growth factor is increased in devascularized rat islets of
      Langerhans in vitro.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen
      with potent angiogenic and vascular permeability-inducing properties, both of
      which may be important for the function of islets of Langerhans. In this study,
      we have examined the expression of VEGF and its tyrosine kinase receptors (flt
      and flk-1) in isolated rat islets of Langerhans in vitro. When analyzed by in
      situ hybridization, islet tissue showed a significant 4.6-fold increase in VEGF
      mRNA expression over time in culture from 0 to 7 days. Islet tissue exposed to
      hypoxic/anoxic conditions for a period of 8 hr showed a 3.7-fold increase in VEGF
      mRNA when analyzed by Northern blot hybridization. Reverse transcriptase
      polymerase chain reaction revealed the presence of both flt and flk-1 in freshly
      isolated islets, and two VEGF isoforms, namely VEGF120 and VEGF164. Three rodent
      beta-cell lines derived from insulinomas (RINm5F-2A, INS-1, and MIN6) were also
      found to express VEGF by Northern blot hybridization. However, neither
      hypoxia/anoxia nor low (0.3 g/L)- or high (3.0 g/L)-glucose culture conditions
      modulated their expression of VEGF. VEGF derived from RINm5F-2A cells was
      bioactive in a three-dimensional in vitro model of angiogenesis, which assays for
      endothelial cell invasion and capillary morphogenesis. These findings
      demonstrate, first, that devascularization increases VEGF expression in isolated
      islet tissue, and they point to VEGF as a potentially important endogenous
      angiogenic stimulus for subsequent revascularization in vivo. Second, our
      observations raise the possibility that survival of transplanted islets may be
      improved by increasing VEGF expression before transplantation.

PMID- 9039937
TI  - Murine marrow coexpressing H2-Dsp2 and H2-Db on host natural killer cell
      rejection.
AB  - BACKGROUND: Class I molecules may inhibit or activate natural killer (NK) cells.
      H2-Dd, -Ld, or -Dsp2 (the latter derived from spretus mice) on bone marrow cells
      (BMC) are recognized and rejected by NK1.1+ NK cells. BMC of intra-H2
      recombinants between H2sp2 and H2b were analyzed. The 9347 and R40
      KbIbBat2b/Tnf(sp2)Dsp2 BMC were rejected by B6 hosts. However, B6 hosts reject
      and accept KbDsp2Db R40 x B6 and 9347 x B6 BMC, respectively. Thus, Db and/or H2
      Bat2/Tnf interval genes may regulate the immunogenicity of H2-Dsp2+ BMC. METHODS:
      R40 or 9347 mice were crossed with DBA.Db (H2d, Db) transgenic mice to produce F1
      and F2 progeny. DNA synthesis (proliferation) in host spleens was the measure of
      marrow graft success. Results. (1) BMC of H2(9347 or R40)+ H2d-Db+ (but not Db-)
      F2 progeny grew in B6 hosts. (2) BMC of H2(9347 or R40) x DBA.Db F1 Kb/dDsp2/dDb
      progeny were rejected by B6, but not by B6D2F1 (H2b/d) or D8 (H2b, Dd) hosts. (3)
      NK cells were the effectors. CONCLUSIONS: Db can reduce the immunogenicity of
      Dsp2+ BMC (F2 data), but not of Dd+ BMC (F1 data). Growth of F2 H2(R40) Db+, but
      not F1 R40 x B6, BMC grafts in B6 hosts could be based on gene(s) differences in
      the H2-Bat2/Tnf region. Alternatively, non-H2 genes of DBA/2 might be involved.
      The genes would provide peptides for Db heavy chains to form "protective motifs"
      that send negative signals to host NK cells.

PMID- 9039938
TI  - No attenuation of ischemic and reperfusion injury in Kupffer cell-depleted, cold
      preserved rat livers.
AB  - Activated Kupffer cells (KC) have been implicated in the damage sustained by
      preserved liver grafts during ischemia and reperfusion. The aim of this study was
      to compare ischemia/reperfusion injury in preserved, KC-depleted rat livers and
      preserved control livers, with special regard to sinusoidal endothelial cell
      (SEC) injury. Wistar rats were injected with liposome-encapsulated
      dichloromethylene diphosphonate, 48 hr before hepatectomy, to eliminate KC, or
      were withheld this pretreatment (controls). Livers were flushed with cold
      University of Wisconsin solution and after 0, 8, 16, or 24 hr of storage at 4
      degrees C, were reperfused in a recirculation system with 200 ml of oxygenated
      Krebs-Henseleit solution at 37 degrees C for 90 min. Damage to SEC was measured
      by the uptake of hyaluronic acid (HA) from the perfusate and release of purine
      nucleoside phosphorylase (PNP). Perfusate samples were, furthermore, analyzed for
      aspartate aminotransferase (AST) and tumor necrosis factor-alpha. Carbon
      particles were infused in the perfusate to determine the phagocytotic capacity of
      KC. Biopsies were taken for histological examination and sections were stained
      with ED2 monoclonal antibodies to confirm the absence of KC. After 90 min of
      reperfusion, immediately after cold flush (t0), the uptake of HA was 72.2+/-2.3%
      and 69.3+/-1.3% in KC-depleted livers and in control livers, respectively (n.s.).
      After 8 hr of storage, HA uptake was 21.6+/-4.5% and 34.6+/-8.0%, respectively
      (n.s.). After 16 and 24 hr of storage and reperfusion, no uptake of HA was found
      in either KC-depleted or control livers, indicating abolished SEC function. PNP
      activities in the perfusate were higher in control livers (after 8 and 24 hr of
      storage), presumably due to release from damaged KC. No difference was found in
      AST and no tumor necrosis factor-alpha was measured in the perfusates of normal
      and KC-depleted livers. Electron microscopic studies showed that after 8 and 24
      hr of storage and reperfusion, KC were activated and were able to phagocytose
      colloidal carbon. Our conclusion was that the elimination of Kupffer cells did
      not result in reduction of ischemic and reperfusion damage in livers preserved up
      to 24 hr, as assessed in vitro by SEC uptake of HA, PNP release, and AST release.

PMID- 9039939
TI  - Visualization of liver sinusoidal endothelial cell repair behavior after
      preservation by in vitro time-lapse video microscopy.
AB  - Sinusoidal endothelial cells are significantly more vulnerable to cold storage
      and reperfusion than hepatocytes. In this study, a method for assessing the
      repair behavior of sinusoidal endothelial cells in vitro, after preservation, was
      investigated. Time-lapse video microscopy analysis was performed and migration
      rates, division rates, and cell detachment rates were determined. Preservation
      intervals between 3 and 24 hr and reoxygenation times between 4 and 24 hr were
      compared. A comparison between sinusoidal endothelial cultures that were stored
      for 6 hr in University of Wisconsin solution and nonpreserved control cultures
      was performed. This method allows the investigation of the repair capability of
      individual cells in vitro. Indications of the kind of preservation/reoxygenation
      injury that occurs after treatment with several preservation solutions and the
      resultant repair behavior can be obtained.

PMID- 9039940
TI  - Fluorescence videomicroscopic assessment of xenogeneic microcirculation and
      impact of antibody removal by immunoadsorption.
AB  - BACKGROUND: Alterations in microcirculation are considered central to the
      pathogenesis of hyperacute xenogeneic rejection (HXR) of vascularized xenografts,
      but currently there exist no data describing these microhemodynamic alterations.
      METHODS: Rat livers were perfused in situ with either isogeneic rat blood or
      xenogeneic human blood. The microcirculation of these xenoperfused livers was
      investigated directly using intravital fluorescence microscopy, and compared with
      that of isogeneic hemoperfused livers. In addition, the impact of antibody
      depletion by immunoadsorption was investigated. RESULTS: Although a homogenous
      microcirculation was found during isogeneic liver perfusion (index of acinar
      perfusion 90.4%/sinusoidal perfusion rate 93.6%), xenoperfusion resulted in a
      rapid breakdown of the microcirculation (47.5%/67.1%, respectively). Perfusion
      deficits were found predominantly in the periportal areas. Immunoadsorption
      reduced the total amount of IgM and IgG by 75.2% and 96.2%, respectively, and
      caused a significantly improved liver perfusion (80.2%/84.4%) and liver function,
      as indicated by bile production. In contrast, the massive hepatic leukocyte and
      platelet accumulation observed during perfusion with untreated xenogeneic blood
      was not altered by antibody depletion. CONCLUSIONS: Thus, the combination of
      isolated rat liver perfusion and intravital fluorescence microscopy enables the
      observation and quantification of the early phase of HXR. This is an important
      step forward for sensitive characterization of the rejection process and will
      enable the mechanisms involved in HXR to be elucidated. Antibody depletion was
      shown to improve liver function and perfusion, but did not reconstitute liver
      viability to the level of the isogeneic perfusion. These findings highlight the
      need for additional therapeutic regimens in xenografting.

PMID- 9039941
TI  - Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF
      kappa B activation.
AB  - Interleukin (IL) 6 is one of major mediators of inflammation, and IL-6 gene
      activation during hypoxia/reoxygenation has been implicated in the pathogenesis
      of ischemia/reperfusion injury. However, molecular events involved in IL-6 gene
      expression during hypoxia/reoxygenation remain to be identified. We have
      previously shown that NF-kappa B plays an essential and indispensable role in the
      transcriptional activation of the IL-6 gene induced by various stimuli, including
      IL-1 and tumor necrosis factor-alpha. We show here that hypoxia, but not
      reoxygenation, induces the activation of NF-kappa B through the degradation of a
      major inhibitor of NF-kappa B, I kappa B alpha. This hypoxia-induced NF-kappa B
      activation resulted in the kappa B-dependent transcriptional activation of the IL
      6 gene. Interestingly, the time course of hypoxia-induced NF-kappa B activation
      was rather slow as compared with those of NF-kappa B activation induced by other
      stimuli, such as IL-1: a significant NF-kappa B activation was not observed
      before 1 hr of hypoxia treatment and persisted for up to 7 hr of hypoxia
      treatment. However, hypoxia-induced NF-kappa B activation was not inhibited by
      cycloheximide, which indicates that hypoxia directly triggers NF-kappa B
      activation. Furthermore, while hypoxia is unlikely to generate reactive oxygen
      intermediates, pretreatment of cells with antioxidants such as N-acetyl cysteine
      and alpha-tocopherol inhibited NF-kappa B activation induced by hypoxia. Thus, we
      discuss possible implications of these results for a postulated role of reactive
      oxygen intermediates in NF-kappa B activation.

PMID- 9039942
TI  - Venous-right atrial bypass for superior vena cava thrombosis during orthotopic
      liver transplantation.

PMID- 9039943
TI  - Human islet allografts in patients with type 2 diabetes undergoing liver
      transplantation.
AB  - BACKGROUND: Most patients with cirrhosis have insulin resistance and impaired
      glucose tolerance, and 20% eventually develop diabetes. Although diabetes in this
      setting may be reversible after orthotopic liver transplantation (OLTx),
      immunosuppressive agents administered after transplantation could exacerbate this
      disease. We report the results of the first pilot trial of islet cell
      transplantation (ICTx) in patients with diabetes undergoing OLTx. METHODS: Five
      patients with diabetes and liver cirrhosis underwent OLTx and ICTx. Donor bone
      marrow cells were also infused to enhance the acceptance of the graft. We
      identified seven patients who received only OLTx and donor bone marrow cells as
      historical controls. RESULTS: Preliminary results suggest that ICTx in
      conjunction with OLTx may improve glucose metabolism (insulin requirement,
      hemoglobin A1c) in patients with liver cirrhosis. However, there was virtually no
      change in pre- and posttransplant basal C-peptide levels in the recipients of
      OLTx + ICTx. CONCLUSIONS: We are planning to further evaluate the effect of OLTx
      with or without ICTx in a randomized prospective trial, using euglycemic insulin
      clamp studies.

PMID- 9039944
TI  - Development of ganciclovir resistance during treatment of primary cytomegalovirus
      infection after liver transplantation.

PMID- 9039945
TI  - Intravenous or intramuscular anti-HBs immunoglobulin for the prevention of
      hepatitis B reinfection after orthotopic liver transplantation.
AB  - To prevent reinfection with hepatitis B virus after orthotopic liver
      transplantation, patients receive long-term intravenous anti-HBs
      immunoprophylaxis. We compared the pharmacokinetics of intravenously and
      intramuscularly administered commercially available hepatitis B virus
      immunoglobulins. The study group consisted of 12 patients on immunoprophylaxis
      after orthotopic liver transplantation, who were Hbs antigen negative; 11 were
      anti-HBe positive and one was HBe positive. The patients first received
      intravenous immunoglobulin, and six of them were then transferred to
      intramuscular immunoglobulin. Our findings show that with fortnightly
      intramuscular application of 1000 IU of anti-HBs, reproducible and stable
      antibody titers above 100 IU of anti-HBs can be achieved. Side effects of
      intramuscular immunoprophylaxis are minimal and the method is safe. The switch
      from intravenous (1500 IU of anti-HBs) to intramuscular (1000 IU of anti-HBs)
      reduced the cost of immunoprophylaxis by more than 50%.

PMID- 9039946
TI  - alpha 1-antitrypsin deficiency-associated panniculitis: resolution with
      intravenous alpha 1-antitrypsin administration and liver transplantation.
AB  - Panniculitis is a rare complication of alpha 1-antitrypsin (A1AT) deficiency that
      is characterized by acute inflammatory infiltrate and fat necrosis. Different
      treatment strategies are used to provide symptomatic relief. Here we describe two
      patients with homozygous A1AT deficiency who developed panniculitis and were
      successfully treated with A1AT replacement. The patient who received a liver
      transplant experienced complete resolution of the skin lesions. The patient who
      received A1AT intravenously showed complete response, but the skin lesions
      recurred when the levels of A1AT fell below 50 mg/100 ml. Panniculitis secondary
      to A1AT deficiency can be successfully treated with liver transplantation or
      intravenous infusion of A1AT.

PMID- 9039947
TI  - Partial splenic embolization in the treatment of thrombocytopenia after liver
      transplantation.

PMID- 9039948
TI  - The pathogenicity of hepatitis G.

PMID- 9039949
TI  - Hepatic allograft injury in erythropoietic protoporphyria.

PMID- 9039950
TI  - Myocardial pseudovascular tubes are present in the delayed rejection of heart
      xenografts.

PMID- 9039951
TI  - Ectonucleotidases, purine nucleoside transporter, and function of the bile
      canalicular plasma membrane of the hepatocyte.
AB  - Ectonucleotidases are enzymes that degrade extracellular nucleotides.
      Extracellular nucleotides (especially ATP) and their degradation products
      (particularly adenosine) have multiple effects on cell functions by acting
      through purinergic receptors. Adenosine nucleotides are present in bile, which
      suggests that hepatocytes may release nucleotides into the canaliculus where they
      are promptly degraded into adenosine by ecto-ATPase and 5'-nucleotidase, which
      have been identified in the canalicular plasma membrane. Adenosine is then
      transported into hepatocytes by a Na+-dependent nucleoside transporter that is
      present in the canalicular plasma membrane. Purification and molecular cloning of
      ecto-ATPase and other canalicular proteins are complicated by an abundant
      canalicular plasma membrane protein, cCAM 105. However, the recent cloning of an
      ecto-ATPase (apyrase) from potato tubers provides a new opportunity to identify
      the canalicular ecto-ATPase. The canalicular Na+-dependent purine nucleoside
      transporter has been cloned from rat liver. Study of its expression during
      development and other physiological circumstances suggests that the transporter
      may play an important role in maintaining hepatic purine levels that are
      essential for the liver to serve as a major source of purines for tissues (i.e.,
      brain, muscle) that lack pathways for de novo purine biosynthesis.

PMID- 9039952
TI  - Regulation of expression of the rodent cytosolic sulfotransferases.
AB  - Understanding the molecular regulation of the sulfotransferases is important
      because these enzymes are essential to a number of critical biological processes.
      Sulfotransferase expression clearly plays a role in xenobiotic detoxication,
      carcinogen activation, prodrug processing, cellular signaling pathways, and the
      regulation of intratissue active androgen and estrogen levels. Although cytosolic
      sulfotransferases are present in the gut, adrenal, kidney, lung, skin, brain, and
      other extrahepatic tissues, the basis for the molecular regulation of this
      complicated gene family has been best characterized in the rat liver, where
      sulfotransferase levels are relatively abundant. Advances in genomic cloning and
      in the molecular characterization of individual sulfotransferase cDNAs have
      inspired new insights into the mechanisms involved in sulfotransferase gene
      regulation. In particular, the hypothalamic-pituitary-gonadal-adrenocortical axis
      appears to play a significant role in the regulation of individual
      sulfotransferase genes. The molecular signals that fluctuate with developmental
      age, gender, and the occurrence of systemic endocrinopathies also influence
      sulfotransferase gene expression. For example, diabetes, which disrupts glucose
      and ketone homeostasis, insulin sensitivity, gonadal and neuroendocrine hormone
      balance, protein kinase C isoform expression, and P450 metabolism, also disturbs
      hepatic sulfotransferase gene expression. What role does sulfotransferase
      expression play in target organ toxicity? Do xenobiotic-mediated changes in
      sulfotransferase expression compromise detoxication? Does deregulated
      sulfotransferase expression during development lead to birth defects by
      perturbing the delicate balance of active hormone levels in fetal tissues? Do
      conditions of glucocorticoid excess, such as stress or high-dose glucocorticoid
      therapy induce sulfotransferase expression and place toxicant and carcinogen
      bioactivation systems in overdrive? This review will summarize our current
      understanding of the molecular and cellular regulation of the major rodent
      cytosolic sulfotransferases. Only by thoroughly dissecting the regulation of this
      important multigene family in rodent liver, where sulfotransferase expression is
      most abundant, can we begin to focus on more pressing questions concerning the
      role of the sulfotransferases in the genesis of endocrinopathies and cancer in
      humans.

PMID- 9039953
TI  - An essential role for free radicals and derived species in signal transduction.
AB  - It is well accepted that extracellular ligands trigger nuclear signals through a
      cascade of protein-protein interactions. Many of these pathways have been
      carefully defined and provide an important framework by which we can understand
      and intervene in the processes they initiate. Recent data in the literature
      indicate that many extracellular ligands generate and/or require reactive free
      radicals or derived species to successfully transmit their signals to the
      nucleus. Thus, a novel signaling mechanism akin to one solely dependent on
      protein-protein interactions may exist. Here, we review this information,
      identify both the sources and targets of free radicals generated by various
      growth factors and cytokines, discuss how specificity can be achieved, and
      explore the pathophysiological implications.

PMID- 9039954
TI  - Heritable diseases of the skeleton. Part I: Molecular insights into skeletal
      development-transcription factors and signaling pathways.
AB  - The recent identification of the genetic basis of hereditary skeletal disorders
      is providing important insights into the intricate processes of skeletal
      formation, growth, and homeostasis. These processes include patterning events
      during condensation and differentiation of mesenchymal cells to form cartilage
      precursors of the future bones, the replacement of cartilage by bones through
      endochondral ossification, the growth of long bones through proliferation and
      differentiation of chondrocytes in growth plates, and bone formation through
      differentiation of osteoblasts from mesenchymal cells in areas of intramembranous
      ossification. Defects in any of these processes can give rise to skeletal
      abnormalities. Mutations in transcription factors such as HOX and PAX and members
      of the transforming growth factor-beta superfamily cause disorders associated
      with abnormal mesenchymal condensation, whereas defects in the transcription
      factor SOX-9 lead to abnormalities in chondrocyte differentiation. Abnormal
      growth plate function, resulting in dwarfism, is the consequence of mutations in
      receptors for fibroblast growth factors and parathyroid hormone-related peptide.
      Premature closure of cranial sutures in intramembranous ossification is a feature
      of syndromes due to mutations in fibroblast growth factor receptors.

PMID- 9039955
TI  - Plant-type ferredoxin-NADP+ reductases: a basal structural framework and a
      multiplicity of functions.
AB  - Ferredoxin-NADP+ (oxido)reductase (EC 1.18.1.2, FNR) is an FAD-containing enzyme
      that catalyzes the reversible electron transfer between NADP(H) and electron
      carrier proteins such as ferredoxin and flavodoxin. Isoforms of this flavoprotein
      are present in chloroplasts, mitochondria, and bacteria in which they participate
      in a wide variety of redox metabolic pathways. Although ferredoxin-NADP+
      reductases have been thoroughly investigated and their properties reviewed on
      several occasions, considerable advances in the understanding of these
      flavoenzymes have occurred in the last few years, including the characterization
      of cDNA and genomic clones encoding FNR proteins from plants, algae, vertebrates,
      and bacteria, determination of the atomic structure of a plant FNR at high
      resolution, and the expression of functional reductases in microorganisms like
      Escherichia coli and Saccharomyces cerevisiae. The aim of this article is to
      summarize information gained through these recent developments, including the
      phylogenetic relationships among ferredoxin reductases and the key structural
      features of the plant FNR family. Other aspects such as the catalytic mechanism
      of FNR and the molecular events underlying biogenesis, intracellular sorting,
      folding, and holoenzyme assembly of this important flavoenzyme are also discussed
      in some detail. Ferredoxin-NADP+ reductases display several outstanding
      properties that make them excellent model proteins to address broad biological
      questions.

PMID- 9039956
TI  - The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic
      cells.
AB  - The widely abused amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA,
      also called "ecstasy") induces hallucination and psychostimulation, as well as
      long-term neuropsychiatric behaviors such as panic and psychosis. In rodents and
      monkeys, MDMA is cytotoxic to serotonergic neurons, but this is less clear with
      humans. Herein, MDMA was cytotoxic to human serotonergic JAR cells; it altered
      the cell cycle, increased G2/M phase arrest, and induced DNA fragmentation in a
      cycloheximide-sensitive way. This apoptosis was not observed in nonserotonergic
      human NMB cells. The stereospecific effect of amphetamines in JAR cells, and the
      key role of NO and dopamine in MDMA-induced apoptosis were determined. The
      relevancy of MDMA-induced cell death to drug users is discussed.

PMID- 9039957
TI  - Helical epitopes determined by low-stringency antibody screening of a
      combinatorial peptide library.
AB  - Combinatorial phage display peptide libraries are routinely used to map epitopes
      of specific monoclonal antibodies. In this study we illustrate that these
      libraries can be used in the analysis of protein structure. By screening
      libraries at low stringency, a collection of phages can be obtained. These are
      characterized by the fact that they are recognized by a given monoclonal antibody
      yet with various affinities. Comparing the random peptides of these phages
      indicates the common essential residues necessary for antibody recognition.
      Aligning the inserts based on the detected homology has revealed structural
      motifs that correspond to secondary protein structures. The envelope protein of
      HIV-1 has been studied using this approach. A combinatorial phage display library
      containing a 20 mer random peptide in protein III of the filamentous phage fd-tet
      has been used to analyze two different monoclonal antibodies directed against
      gp120. Our results provide experimental evidence that indicate that the C1 domain
      of gp120 contains an alpha helix.

PMID- 9039958
TI  - Impairment of excitatory amino acid transporter activity by oxidative stress
      conditions in retinal cells: effect of antioxidants.
AB  - In the present study we analyzed how oxidative stress conditions induced by
      ascorbate/ Fe2+ affect the excitatory amino acid (EAA) transport systems in
      cultured chick retina cells. The uptake of D-[3H]aspartate, which is transported
      by the same carrier as glutamate, was determined in control cells and in cells
      subjected to ascorbate/Fe2+. The uptake of this EAA was Na+ dependent and was
      inhibited by about 40% under oxidative stress conditions. To clarify the
      molecular mechanisms involved in the inhibition of D-[3H]aspartate uptake by
      ascorbate/Fe2+, we investigated the effect of vitamin E (Vit E), melatonin,
      reduced glutathione (GSH), and dithiothreitol (DTT) on the uptake of D
      [3H]aspartate and on the extent of lipid peroxidation in control and in
      peroxidized cells. Preincubation with Vit E (100 microM) abolished lipid
      peroxidation, but had no significant effect on the inhibition of D-[3H]aspartate
      uptake evoked by ascorbate/Fe2+. Melatonin was more effective in reducing the
      formation of TBARS and conjugated dienes than in preventing the D-[3H]aspartate
      uptake inhibition evoked by the oxidant pair. Conversely, GSH (4 mM) and DTT (4
      mM) completely prevented the inhibition of D-[3H]aspartate uptake in cells
      subjected to oxidative stress, but were without effect on the extent of
      peroxidation. Free fatty acids, such as arachidonic acid, seem not to be involved
      in reducing the activity of the D-[3H]aspartate uptake system, whereas the
      reduction of the Na+ electrochemical gradient that occurs under oxidative stress
      was in part involved in the reduction of D-[3H]aspartate uptake by the cells. The
      inhibition of D-[3H]aspartate uptake by ascorbate/Fe2+ persisted for at least 1
      h, but could be partially reverted by disulfide reducing agents. It is concluded
      that oxidative stress causes long-lasting modifications of the glutamate/D
      [3H]aspartate transport system (or systems), such as oxidation of protein
      sulfhydryl (SH) groups, which can be recovered by some antioxidants.

PMID- 9039959
TI  - Computation of the binding of fully flexible peptides to proteins with flexible
      side chains.
AB  - Docking algorithms play an important role in the process of rational drug design
      and in understanding the mechanism of molecular recognition. An important
      determinant for successful docking is the extent to which the configurational
      space (including conformational changes) of the ligand/receptor system is
      searched. Here we describe a new, combinatorial method for flexible docking of
      peptides to proteins that allows full rotation around all single bonds of the
      peptide ligand and around those of a large set of receptor side chains. We have
      simulated the binding of several viral peptides to murine major
      histocompatibility complex class I H-2Kb. In addition, we have explored the
      limits of our method by simulating a complex between calmodulin and an 18-residue
      long helical peptide from calmodulin-dependent protein kinase IIalpha. The
      calculated peptide conformations generally matched well with the X-ray
      structures. Essential information about local flexibility and about residues that
      are responsible for strong binding was obtained. We have frequently observed
      considerable side-chain flexibility during the simulations, showing the need for
      a flexible treatment of the receptor. Our method may also be useful whenever the
      receptor side-chain conformation is not available or uncertain, as illustrated by
      the docking of an H-2Kb binding nonapeptide to the receptor structure taken from
      an octapeptide/H-2Kb complex.

PMID- 9039960
TI  - Expression of a disintegrin-like protein in cultured human vascular cells and in
      vivo.
AB  - Metalloproteinase-like, disintegrin-like, and cysteine-rich proteins (MDCs) are
      potential novel regulators of cell-cell and cell-matrix interactions, as well as
      of matrix degradation. We have asked whether MDCs are expressed in cultured
      diploid vascular cells, and have identified MDC 15 in human aortic smooth muscle
      (SMC) and umbilical vein endothelium (HUVEC). MDC 15 mRNA is expressed at higher
      levels in HUVECs than in SMCs. In cultured SMCs, MDC 15 mRNA levels are not
      regulated by PDGF or IGF-I or by adherence to different extracellular matrices.
      Nor is regulation of MDC 15 mRNA levels observed in HUVEC monolayers at different
      cell densities, after multi-scratch wounding, or after treatment with TNF-alpha,
      LPS, or thrombin. However, differences in proteolytic processing of MDC 15 are
      observed in different HUVEC strains. In contrast to cultured arterial cells, MDC
      15 protein is not expressed in vivo in normal vessels, but is up-regulated in
      lesions of atherosclerosis. These findings suggest that MDC 15 may be a potential
      regulator of vascular cell function and may be involved in the development of
      lesions of atherosclerosis.

PMID- 9039961
TI  - Aldose reductase induction: a novel response to oxidative stress of smooth muscle
      cells.
AB  - Hydrogen peroxide (H2O2) or 4-hydroxy-2,3-trans-nonenal (HNE) treatment of rat
      vascular smooth muscle cells (A7r5) caused induction of aldose reductase mRNA.
      Induction was dose (10-100 microM H2O2, 1-10 microM HNE) and time dependent,
      reaching a maximum (three- to fourfold) after 7-12 h. Treatment of cells with
      actinomycin D confirmed de novo synthesis of aldose reductase mRNA. H2O2-induced
      expression was prevented by catalase but unaffected by Desferal, indicating that
      metal catalyzed degradation of peroxide was not involved. Induction of
      enzymatically active aldose reductase by H2O2 and HNE was confirmed using Western
      blotting and enzyme assays. Aldose reductase can metabolize several aldehyde
      compounds including HNE, a major toxic product of lipid peroxidation. Inclusion
      of Sorbinil, an aldose reductase inhibitor, in toxicity assays resulted in a
      significant (twofold) enhancement of HNE-mediated killing of A7r5 cells,
      suggesting a protective role of aldose reductase against HNE-induced cell death.
      These data indicate that the induction of aldose reductase during oxidative
      stress might represent an important cellular antioxidant defense mechanism.

PMID- 9039963
TI  - Animal models for the study of perinatal hypoxic-ischemic encephalopathy: a
      critical analysis.
AB  - We critically evaluated various design features from 292 animal studies related
      to perinatal hypoxic-ischemic encephalopathy (HIE). Rodents were the most
      frequently used animals in HIE research (26%), followed by piglets (23%) and
      sheep (22%). Asphyxia with or without ischemia was the most predominant method of
      producing experimental brain damage, but there were significant variations in
      specific details, particularly regarding the method and duration of brain insult.
      In 71% (207/292) of studies the CNS outcomes were tested within 24 h of
      experimental insult and in 29% (85/292) they were tested 24 h or more after the
      insult. Acute CNS metabolic end-points were assessed in 82-100% of all studies.
      In 90% of studies the chronological age of the animal was equivalent to that of
      human term newborn infant. However, in only 23% (67/292) were clinical
      neurological, developmental or behavioral outcomes evaluated, and in only 26%
      (76/292) was neuropathology assessed. While no single animal model was found to
      be ideal for all HIE research, some models were distinctly superior to others,
      depending upon the specific research question. The fetal sheep, newborn lamb and
      piglet models are well suited for the study of acute and subacute metabolic and
      physiologic endpoints, whereas the rodent and primate models could be used for
      long-term neurological and behavioral outcome experiments as well. We also feel
      that standardizing the study design features, including an HI insult method that
      produces consistent and predictable brain damage is urgently needed. Studies in
      neuro-ethology should explore how well brains of various animals compare with
      that of the newborn human infant. There is also a need for developing animal
      models that mimic clinical entities in which long-term neuro-developmental and
      behavioral outcomes can be assessed.

PMID- 9039962
TI  - The G-protein G(i) regulates mitosis but not DNA synthesis in growth factor
      activated fibroblasts: a role for the nuclear translocation of G(i).
AB  - GTP binding proteins, heterotrimeric molecules composed of alpha-, beta-, and
      gamma-subunits, are known to serve as transducers of information from seven
      transmembrane receptors. Activation of G-proteins has been generally considered
      to involve subunit dissociation, with G(alpha) separating from G(betagamma).
      However, we have found a receptor activation of G(i) in proliferating cells that
      differs from these models and involves the subcellular translocation of the alpha
      subunit from the cell periphery to the nucleus where G(i alpha) binds to
      chromatin for the duration of mitosis. This report describes the mechanism of
      G(i) activation in Swiss 3T3 cells in response to serum, thrombin, and epidermal
      growth factor, and describes a role for G(i2) in the cell cycle. Agonists were
      found to be unable to induce the physical dissociation of G(i2) subunits. The
      alpha- and beta-subunits of G(i2) could be coimmunoprecipitated with a G(i alpha)
      antibody from both the membrane and nuclear fractions of long-term activated
      cultures, showing that G(i alpha 2) and G(i beta) are induced to comigrate to the
      nucleus in response to growth factor receptor activation. G(i2) appears to be
      activated in part by a postreceptor signal that can be mimicked by protein kinase
      C activation; this signal may be responsible for the convergence of the signaling
      mechanisms of these distinct seven-transmembrane and tyrosine kinase receptors.
      We suggest that translocation of G(i alpha) to the nucleus induced by either
      thrombin or EGF may occur without subunit dissociation. Functional studies of the
      role of G(i) showed that pertussis toxin does not block DNA synthesis in Swiss
      3T3 fibroblasts induced by serum or thrombin, but that cell proliferation is
      retarded to each. These results provide direct evidence for a novel mechanism of
      GTP binding protein activation and for an essential role of G(i) in the induction
      of cell division by a variety of growth factor receptors. G(i) can carry out this
      role in control of cellular proliferation through its translocation to the
      nucleus of mitotic cells.

PMID- 9039964
TI  - The c-ets1 protooncogene is expressed in human trophoblast during the first
      trimester of pregnancy.
AB  - Expression of the c-Ets1 protooncogene which codes for a transcription factor is
      associated with neovascularization and invasive processes. In order to determine
      c-Ets1 expression at the mRNA level, during the process of implantation during
      the first trimester of human pregnancy, samples of trophoblast were retrieved at
      the time of legal abortion and processed for in situ hybridization. We found that
      c-Ets1 mRNAs are transcribed in the endothelial cells of villous trophoblast and
      in the extravillous trophoblastic cells invading the uterine vessels. However, no
      transcript was found in maternal endothelial cells. We conclude that c-Ets1 plays
      a role in angiogenesis occurring in the development of the villous tree and is
      involved during the invasive process of the endometrium and maternal vessels by
      trophoblastic cells; this latter physiological event is crucial for a normal
      development of the fetus, its failure leading to pathological cases. We suggest
      that the role of the c-Ets1 protooncogene is related to the regulation of
      metalloproteinase genes transcription, a gene family which is known to be a
      target for Ets protein.

PMID- 9039965
TI  - Intrauterine growth correlation to postnatal growth--influence of risk factors
      and complications in pregnancy.
AB  - In a population of 616 pregnant women with increased risk of intrauterine growth
      retardation, we examined the relationship of third trimester fetal growth to
      maternal and pregnancy risk factors, the infants condition at birth, and
      postnatal growth. Intrauterine growth velocity was calculated from repeated
      estimations of fetal weight using ultrasound. Postnatal growth up to 3 months was
      measured in 313 of the infants. Intrauterine growth velocity was directly
      correlated to birth weight deviation (R = 0.35, P < 0.0001) and inversely
      correlated to postnatal growth (R = 0.21, P = 0.0001). Heavy smoking throughout
      pregnancy was the most pronounced factor associated with loss of fetal growth
      percentiles (P = 0.006), and it was also associated with postnatal catchup (P =
      0.01). Infants who needed neonatal care had significantly lower intrauterine
      growth velocities compared to the rest of the study group; no correlation was
      found between intrauterine growth velocity and Apgar scores or umbilical pH. It
      is concluded that growth retardation in the third trimester can be identified by
      ultrasound fetometry, and is associated with maladaptation at birth and postnatal
      catchup. However, the correlations were weak suggesting that deviation at birth
      reflects, only to a limited degree, acceleration or deceleration of growth in the
      third trimester.

PMID- 9039966
TI  - Effect of dexamethasone on rat plasma platelet activating factor acetylhydrolase
      during the perinatal period.
AB  - It has been previously reported that the administration of dexamethasone (DEX) to
      adult rats increases the activity of plasma platelet-activating factor
      acetylhydrolase (PAF-AH) and prevents the development of intestinal necrosis
      caused by platelet activating factor (PAF) injection. In this report, we examined
      the effect of DEX administration on plasma PAF-AH activity during the perinatal
      period. Timed-pregnant rats received DEX (0.2-1.0 mg/kg/d) or normal saline
      (controls) on days 16-18 (early group) or days 18-20 (late group) of gestation.
      Maternal plasma PAF-AH activity was lower in late gestation than in postpartum
      period (P < 0.001). Fetal and neonatal plasma PAF-AH activity was higher than
      maternal values (P < 0.05). No changes of PAF-AH activity were seen in maternal,
      fetal or neonatal plasma after prenatal DEX administration at the aforementioned
      doses. A higher dose of DEX (1.3 mg/kg/d x 4d) or cortisone (200 mg/kg/d)
      produced an elevation of maternal plasma PAF-AH activity (DEX 79.2+/-3.0,
      cortisone 70.5+/-1.9 vs. controls 49.4+/-2.3 nmol/min/ml, P < 0.01), but resulted
      in a high fetal mortality. Treatment of newborn rats with DEX (0.5 mg/kg/d) on
      days 1-3 after birth, increased plasma PAF-AH activity on day 4 (DEX 292+/-5
      versus controls 140+/-9 nmol/min/ml, P < 0.001) and day 6 (DEX 302+/-12 versus
      controls 136+/-6 nmol/min/ml, P < 0.001). Postnatal administration of DEX
      increases the plasma PAF-AH activity in the rat. Only high doses of prenatal
      corticosteroids that cause fetal death can elevate maternal plasma PAF-AH
      activity.

PMID- 9039967
TI  - Middle cerebral artery velocimetry as a predictor of hypoxemia in fetuses with
      increased resistance to blood flow in the umbilical artery.
AB  - About half of all fetuses with increased resistance to blood flow, but with still
      detectable diastolic blood velocity in the umbilical artery (UA), show signs of
      imminent asphyxia during labour indicating a need for operative delivery. Fetal
      brain-sparing during hypoxia is characterized by an increase in diastolic and
      mean blood flow velocity in the middle cerebral artery (MCA). The aim of this
      study was to assess whether MCA blood velocity in pregnancies with increased
      resistance to blood flow in the feto-placental circulation could predict the
      development of fetal asphyxia during labour. Fifty pregnant women with signs of
      increased feto-placental vascular resistance between 31 and 42 weeks of gestation
      were studied serially by Doppler ultrasound and the last examination was
      correlated to perinatal outcome. The MCA pulsatility index (PI), cerebroplacental
      PI ratio and mean MCA blood velocity were calculated and correlated to fetal
      outcome. Fetal brain-sparing was defined as MCA PI < mean -2 S.D.,
      cerebroplacental PI ratio < 1.08 and mean MCA blood velocity >mean + 2 S.D. No
      significant association was found between signs of fetal brain-sparing and the
      perinatal outcome. Among fetuses with signs of increased resistance to flow in
      the umbilical artery, velocimetry of the middle cerebral artery did not identify
      those that would not withstand the strain of labour.

PMID- 9039968
TI  - Characterization of the vasodilatatory response to serotonin in human umbilical
      arteries perfused in vitro. The influence of the endothelium.
AB  - In most preparations of human cord arteries perfused in vitro, infusion of 10(-7)
      M of serotonin leads to a biphasic pressure response starting with a transient
      minor vasodilatation followed by a dominant vasoconstriction. In some
      preparations, however, the vasoconstrictive part of the response with this dose
      of serotonin is less pronounced or completely absent, whereas the dilatation is
      stronger and more prominent. The present study deals exclusively with experiments
      on cord arteries displaying the latter type of serotonin reactivity, and was
      undertaken in order to characterize the relaxing effect of serotonin, and in
      particular, the role of the endothelial layer. This was accomplished by studying
      the response pattern before and after treatment with different drugs or removal
      of the endothelium. The vasodilatatory action of serotonin was found to be
      abolished following treatment with methysergide, significantly reduced after
      denudation (P <0.05), slightly reduced after exposure to methylene blue or N
      omega-nitro-L-arginine methyl ester (L-NAME) (non-significantly), but not
      affected by indomethacin. The results suggest that the relaxing effect is
      mediated by specific serotonin receptors and that endothelium-derived substances,
      possibly including nitric oxide, are involved.

PMID- 9039969
TI  - Clinical features of and cardiotocographic findings for premature infants with
      antenatal periventricular leukomalacia.
AB  - OBJECTIVE: To clarify the clinical features of and cardiotocographic findings for
      premature infants with antenatal periventricular leukomalacia (PVL). METHODS:
      Antenatal PVL was judged to be present if a cyst greater than 3 mm in largest
      diameter was detected in the periventricular region by the 14th day of life on
      cranial ultrasonography. The clinical features of and cardiotocographic findings
      for 12 premature infants with antenatal PVL born within 1 year were compared with
      those of 12 infants chosen as control group matched in gestational age at birth
      from the premature infants without antenatal PVL born within the study period.
      RESULTS: Abnormalities of the umbilical cord such as coiling, excessive torsion
      and membrane insertion were observed more frequently for infants with antenatal
      PVL (58.3%) than for control infants (16.7%) (P<0.05). Frequent moderate variable
      deceleration on the fetal cardiogram was also observed more frequently for
      infants with antenatal PVL (80.0%) than for control infants (27.3%) (P<0.05).
      CONCLUSION: Abnormalities of the umbilical cord and frequent moderate variable
      deceleration on fetal cardiotocogram appear to be causes of antenatal PVL in
      premature infants.

PMID- 9039970
TI  - Correlates of low thyroxine values at newborn screening among infants born before
      32 weeks gestation.
AB  - We assessed the relation of perinatal factors to severe hypothyroxinemia of
      prematurity, defined as thyroxine value more than 2.6 standard deviations below
      the mean for newborns. The 365 survivors of birth before 32 weeks gestation were
      enrolled in a population-based study of the correlates of neonatal brain injury.
      In this historical cohort study, mothers were interviewed; perinatal data were
      abstracted from medical records and neonatal data were collected prospectively.
      Neonatal thyroxine screening values were retrieved from the New Jersey State
      Department of Health. Associated with severe hypothyroxinemia were: gestational
      age 23-27 weeks vs. 31 weeks (OR = 5.1, 95% CI 1.7, 15.2), later age at thyroxine
      test (OR = 1.6 per day, 95% CI 1.2, 2.1), fraction inspired oxygen at age 24 h >
      40% (OR = 3.2, 95% CI 1.1, 8.8), mechanical ventilation (OR = 5.1, 95% CI 1.3,
      19.4), diastolic blood pressure < 20 mmHg (OR = 2.3, 95% CI 1.2, 4.3), and > 12
      years of maternal education (OR = 0.4, 95% CI 0.22, 1.0). Infants with severe
      hypothyroxinemia had higher mortality, more days of oxygen supplementation,
      ventilation and hospitalization and were 11 times more likely to require oxygen
      supplementation at the postnatal age equivalent to 36 weeks gestational age (odds
      ratio 10.6, 95% CI 2.3, 48.8). In preterm infants, neonatal thyroxine levels
      obtained at newborn screening in the first week of life may convey important
      prognostic information about mortality, morbidity, and the risk for
      bronchopulmonary dysplasia.

PMID- 9039971
TI  - Identification and characterization of two groups of congenital hypothyroid
      infants: implications for newborn screening.
AB  - A retrospective analysis of 400 newborns diagnosed with congenital primary
      hypothyroidism between 1983 and 1987 was conducted. Two distinct groups of cases
      were identified and characterized based on their newborn screening TSH value. The
      two groups are separated at a TSH concentration of 50 mU/l of serum by a normal
      probability plot. This finding is in agreement with the 1993 recommendation from
      the American Academy of Pediatrics that infants with a low T4 level and a TSH
      concentration greater than 40 mU/l be considered to have primary hypothyroidism
      until proven otherwise. The group of infants with TSH less than 50 mU/l have a
      higher proportion of males and low birthweight infants. For this group, T4
      increases with increasing TSH. We find that screening TSH, T4, and birthweight
      are predictive of follow-up serum TSH level for the cases with TSH > 50 mU/l but
      not for cases with TSH < 50 mU/l. An optimal rule for selecting screening cutoff
      levels is presented based on only T4, TSH and their interaction. Adjustments for
      sex, birthweight or age at which sample was taken did not aid in distinguishing
      cases from controls for newborns whose age of sample is 2 days or greater.

PMID- 9039972
TI  - Ultrastructural evidence for the participation of Langerhans cells in cutaneous
      photoaging processes: a quantitative comparative study.
AB  - Langerhans cells were studied comparatively by electron microscopy in order to
      explore their possible participation in cutaneous photoaging processes in
      chronically photodamaged preauricular skin and in paired sun-protected
      postauricular sites of 25 Caucasian women aged 56-76 years. The characteristic
      ultrastructural features of Langerhans cells in photodamaged skin compared to
      those in sun-protected skin were as follows: (1) a significant decrease in the
      density of Langerhans cells and Birbeck granules, and an increase in the number
      of indeterminate cells, (2) an inversely proportional relationship between
      intraepidermal density of Langerhans cells and the severity of epidermal
      photodamage, (3) frequent apposition of Langerhans cells to vacuolar structures
      of photodamaged keratinocytes, (4) predominant distribution of Langerhans cells
      in the lower epidermis, (5) degenerative changes suggesting direct cellular
      damage, without evidence of apoptosis, (6) a strong correlation of the number of
      degenerated Langerhans cells with the degree of epidermal photodamage, (7) loss
      of dendritic processes, (8) direct contact of Langerhans cells with melanocytes
      suggesting interaction between these two types of cells, (9) juxtaposition of
      Langerhans cells and lymphocytes in the epidermis. These results suggest marked
      qualitative and quantitative ultrastructural differences in Langerhans cells
      between photodamaged and intrinsically aged skin and the positive involvement of
      Langerhans cells in the processes of cutaneous photoaging.

PMID- 9039973
TI  - Topical liposome delivery of molecules to hair follicles in mice.
AB  - The hair cycle consisting of growing and resting phases, is subject to widespread
      disease such as androgenic alopecia or loss of pigment which are in need of
      effective, targeted therapeutics. In order to develop a hair-follicle delivery
      system we demonstrate here that phosphatidylcholine liposomes entrapping either
      the fluorescent dye calcein or the pigment melanin can deliver these molecules
      into the hair follicle and hair shafts of mice when applied topically. Liposomal
      delivery of these molecules is time dependent. Negligible amounts of delivered
      molecules enter the dermis, epidermis or blood stream thereby demonstrating the
      enrichment of follicle delivery. Naked calcein and melanin are trapped in the
      stratum corneum and are unable to enter the follicle. The potential of the hair
      follicle liposome delivery system for therapeutic use for hair disease is
      discussed.

PMID- 9039974
TI  - Interleukin-1 and lipopolysaccharide enhance intercellular adhesion molecule-1
      expression in cell lines of human squamous cell carcinoma.
AB  - We show that in two cell lines of human squamous cell carcinoma (SCC) which
      slightly express intercellular adhesion molecule-1 (ICAM-1), the expression is
      enhanced not only by interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha
      (TNF-alpha) but also by interleukin-1 (IL-1) and lipopolysaccharide (LPS). This
      expression is totally dependent on the increase of ICAM-1 mRNA. This evidence
      contrasts with previously reported findings indicating that, in human cultured
      keratinocytes, ICAM-1 expression is induced by IFN-gamma and TNF-alpha, and not
      by either IL-1 or LPS. This result suggests that various cytokines or agents
      easily enhance ICAM-1 expression in SCC cell lines, and may explain the clinical
      finding that ICAM-1 expression increases according to the progression of
      malignant tumors.

PMID- 9039975
TI  - A novel approach to the understanding of human skin barrier function.
AB  - The basis for externally caused skin disorders is penetration of the skin
      barrier. A recent model for the skin barrier, the domain mosaic model, based on
      current knowledge of the physics of lipid bilayer organization gave tentative
      explanations for several aspects of function. It is demonstrated here that a
      development of the model explains how the requirements are met for a water-tight
      structure that will still allow a controlled, minute loss of water, the
      perspiratio insensibilis, necessary for maintaining plasticity of the keratin. A
      major advantage of the extended model is that it allows an interpretation of the
      changes imposed on the structure when in contact with detergents and/or
      penetration enhancers.

PMID- 9039976
TI  - Histopathologic features seen with different animal models following cutaneous
      sulfur mustard exposure.
AB  - In an effort to understand the pathophysiology of sulfur mustard (2,2'
      dichlorodiethyl sulfide, HD)-induced cutaneous lesions, a number of animal models
      have been used. Animal models have been and will continue to be used in the
      development of therapeutic strategies to protect against and/or moderate lesions,
      and to potentiate wound healing after HD exposure. Upon reviewing the
      histopathologic features seen after HD-exposure, we propose roles for different
      animal models in HD-research. Hematoxylin and eosin slides from protocols done
      originally as dose response studies for either liquid or vapor HD-exposures were
      examined. The animal models reported include the hairless guinea pig (HGP),
      weanling pig (WP), mouse ear (ME) and hairless mouse (HM). In all these animal
      models. HD induces subepidermal blister formation as well as epidermal cell
      death. The HGP appears to be the most sensitive model for epidermal necrosis. The
      HGP and, to a lesser degree, the HM react with a marked neutrophilic infiltrate.
      The ME provides a quantitative measure for HD effects and a mild inflammatory
      infiltrate similar to what is seen in human skin. Doses necessary to produce
      microblister formation in the WP are usually associated with more significant
      stromal and vascular changes than in other animal models. In addition to a
      quantitative measure of the HD effect and a mild inflammatory response, the cost,
      as well as the availability of specific antibodies, and DNA and RNA probes and
      primers gives the ME advantages for both drug screening and for the study of the
      pathophysiology of HD-induced cutaneous lesions. The sensitivity of the HGP and
      the abundant experience with vapor exposures establishes a place for this animal
      model in barrier cream and drug screening. The similarity of WP skin to human
      skin is important in the study of wound healing after HD exposure, as well as in
      the study of the pathophysiology of the cutaneous lesion and in more definitive
      therapeutic studies.

PMID- 9039977
TI  - Psoralens percutaneous permeation across the human whole skin and the epidermis
      in respect to their polarity (in vitro study).
AB  - 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen
      (TMP) are commonly used in PUVA therapy [psoralen (P) + ultraviolet light A (UVA)
      irradiation] to treat skin diseases such as psoriasis and vitiligo. In order to
      predict the choice of the suitable drug(s) for topical applications, with
      appropriate dosage, percutaneous permeation of the psoralens, in connection with
      their solubilities and partition coefficients in an octanol/water system, were
      investigated. The percutaneous penetration experiments were accomplished by the
      deposit of ethanolic psoralen solution onto human skin and epidermis fragments
      mounted on Franz cells. Six cells were employed for each psoralen solution and
      for the whole skin layer as well as for the epidermis. The diffused psoralens in
      the receptor solution (1.4%, of human serum albumin) were quantified by using
      high performance liquid chromatography. The solubilities and the partition
      coefficients (PC) were carried out in an octanol/water system, in triplicate by
      using spectrofluorimetry. The results demonstrated that cumulated permeated
      quantities (ng/cm2) over 24 h, across the whole skin and the epidermis were in
      the following order for the three psoralens: 8-MOP > 5-MOP > TMP. The
      lipophilicity, expressed via the log PC, was as follows: 1.93 +/- 0.01 (8-MOP),
      2.00 +/- 0.01 (5-MOP) and 3.14 +/- 0.01 (TMP). It was inversely correlated with
      cumulated penetrated amounts over 24 h in both whole skin and epidermis. From
      these results, TMP could be predicted as the most convenient psoralen for topical
      applications, because of its weak penetrability. Considering the relationship
      between psoralens lipophilicity and permeation, only 5-MOP and 8-MOP could be
      used, topically or orally, especially in the case of generalised skin disorders.

PMID- 9039978
TI  - Role of increased production of monocytes TNF-alpha, IL-1beta and IL-6 in
      psoriasis: relation to focal infection, disease activity and responses to
      treatments.
AB  - To evaluate the immunological function of peripheral blood monocytes (PBMC) in
      psoriasis, we measured spontaneous production of the inflammatory cytokines, TNF
      alpha, IL-1beta and IL-6 from the PBMC of psoriasis patients, by enzyme linked
      immunosorbent assay (ELISA). The production of all three inflammatory cytokines
      by psoriatic PBMC was significantly higher than that by normal control PBMC. PBMC
      sampled from active psoriasis produced three cytokines significantly higher than
      samples from inactive psoriasis. In addition, IL-1beta and TNF-alpha production
      showed a positive relation to clinical severity, but IL-6 did not. TNF-alpha
      production increased much more than did the others. Therefore, the TNF-alpha to
      IL-1beta ratio was significantly higher, even in inactive psoriasis, than that of
      the normal control. In relation to focal infection, psoriatic PBMC sampled 3 h
      after a tonsillar provocation test increased cytokine production, compared with
      the level before provocation. The cases which responded to tonsillectomy or
      systemic methotrexate therapy, but not the non-responding cases, showed a
      significant decrease in PBMC cytokine productivity. These results strongly
      suggest that inflammatory cytokines, especially TNF-alpha, from monocytes are
      involved in the pathogenesis of psoriasis, and activated monocytes may work as an
      effective mediator of focal infection in skin lesions.

PMID- 9039979
TI  - Tape stripping induces marked epidermal proliferation and altered TGF-alpha
      expression in non-lesional psoriatic skin.
AB  - Psoriasis is a chronic inflammatory disorder characterized by epidermal
      hyperproliferation. Although recent evidence suggests that T cell activation is a
      primary trigger for psoriasis lesions, there may be alterations in the
      keratinocyte growth regulatory pathways which induce epidermal hyperproliferation
      in psoriatic patients. To test this hypothesis, we investigated the proliferative
      activity of epidermal keratinocytes 48 h after tape stripping, one of the
      standard mechanical ways to stimulate the epidermis, in 20 psoriasis patients and
      in 18 controls. Epidermal cell kinetics were assessed with DNA flow cytometry,
      the mitotic index, bromodeoxyuridine incorporation, Ki-67 antigen expression and
      DNA polymerase alpha expression. The expression of TGF-alpha and EGF receptors,
      critical mediators of keratinocyte proliferation, were also investigated
      immunohistochemically. The results of multiparameter assays showed that the
      baseline proliferative activity in uninvolved skin was the same in psoriasis
      patients and normal controls. After tape stripping, although both psoriasis
      patients and the normal controls showed significant increases in epidermal cell
      proliferation, the values of all the parameters investigated were significantly
      greater in the psoriasis patients than in the normal controls. EGF receptors were
      overexpressed in basal and suprabasal keratinocytes after tape stripping in both
      the psoriasis patients and the normal controls. In contrast, overexpression of
      TGF-alpha was only observed in the patients with psoriasis, which may explain
      their increased proliferative response to trauma.

PMID- 9039980
TI  - Effect of growth factors on dermal fibroblast contraction in normal skin and
      hypertrophic scar.
AB  - We have examined the effects of four 'exogenous' growth factors, i.e. PDGF-BB (5
      ng/ml), TGF-beta1 (5 ng/ml), bFGF (10 ng/ml) and EGF (10 ng/ml) on the
      contraction of floating collagen type I lattices populated by human normal skin
      (NS) and hypertrophic scar (HS) fibroblasts (FPCL). Only TGF-beta1 enhanced the
      contractility of both NS and HS fibroblasts in the collagen lattice (P < 0.01).
      Other growth factors (PDGF-BB, bFGF and EGF) did not affect FPCLs contraction at
      72 h (P > 0.05). The onset effect of TGF-beta1 on NS-FPCL contraction was
      relative early at 24 h after FPCL casting as compared to a 72 h delay on HS-FPCL
      contraction. Besides, PDGF-BB was found to be able to enhance HS-FPCL contraction
      (P < 0.05) but not on NS-FPCL contraction on day 4. On the other hand, three
      enzyme-linked immunosorbent assays (ELISA) were performed to demonstrate
      quantitatively the 'endogenous' growth factors that fibroblasts secreted into the
      culture medium 48 h after FPCL casting. No appreciable difference was found
      between 10 NS and 11 HS samples tested for PDGF-AB immunoassay (11.48 +/- 5.5
      pg/ml versus 12.20 +/- 5.34 pg/ml). The same result existed in 7 NS and 13 HS
      samples for TGF-beta2 immunoassay (15.15 +/- 6.2 pg/ml versus 11.84 +/- 7.46
      pg/ml). In bFGF immunoassay study, relative variable data was noted in both 7 NS
      (18.18 +/- 13.18 pg/ml) and 12 HS samples (20.41 +/- 22.36 pg/ml). In conclusion,
      we suppose that TGF-beta role in wound healing may be due to the secondary
      exogenous influences. The endogenous ability of TGF-beta2 secretion (quantity) in
      HS fibroblasts are the same as NS fibroblasts but with delayed timing responses
      (quality) to exogenous TGF-beta1 effect in the collagen lattice. Further studies
      with timing-regulated selective specific monoclonal antibodies against the growth
      factor receptors may provide the therapeutic applications on HS during wound
      healing.

PMID- 9039981
TI  - Genotype-phenotype relationship in 12 patients carrying cystic fibrosis mutation
      R334W.
AB  - We present a phenotype-genotype correlation analysis in 12 patients with cystic
      fibrosis (CF) carrying the mutation R334W in the CFTR gene. The clinical data
      obtained for this group were compared with the clinical data of
      deltaF508/deltaF508 patients. Current age and age at diagnosis were significantly
      higher in the R334W mutation group (p=0.028 and p=0.0001). We found a lower rate
      of Pseudomonas aeruginosa colonisation in patients carrying the R334W mutation,
      although the difference was not found to be statistically significant. However,
      we found a statistically significant higher age of onset of Pseudomonas
      aeruginosa colonisation (p=0.0036) in the group of patients with the R334W
      mutation. Thirty three percent of R334W patients were pancreatic insufficient,
      significantly lower than the deltaF508/deltaF508 patients (p=0.004). We also
      found that the weight expressed as a percentage of ideal weight for height was
      significantly higher in patients with the R334W mutation (p=0.0028).

PMID- 9039982
TI  - Bardet-Biedl syndrome: a molecular and phenotypic study of 18 families.
AB  - The autosomal recessive disorder Bardet-Biedl syndrome is characterised by
      retinal degeneration, polydactyly, obesity, mental retardation, hypogenitalism,
      renal dysplasia, and short stature. It is heterogeneous with at least four gene
      loci (BBS1-4) having been mapped to date. We have studied 18 multiply affected
      families noting the presence of both major and minor manifestations. Using a
      fluorescently based PCR technique, we genotyped each family member and assigned
      linkage to one of the four loci. Given this degree of heterogeneity we hoped to
      find phenotypic differences between linkage categories. We found 44% of families
      linked to 11q13 (BBS1) and 17% linked to 16q21 (BBS2). Only one family was linked
      to 15q22 (BBS4) and none to 3p12. We conclude that BBS1 is the major locus among
      white Bardet-Biedl patients and that BBS3 is extremely rare. Only subtle
      phenotypic differences were observed, the most striking of which was a finding of
      taller affected offspring compared with their parents in the BBS1 category.
      Affected subjects in the BBS2 and 4 groups were significantly shorter than their
      parents. Twenty eight percent of pedigrees did not show linkage to any known
      locus, evidence for at least a fifth gene. We conclude that the different genes
      responsible for Bardet-Biedl syndrome may influence growth characteristics such
      as height.

PMID- 9039983
TI  - Refinement of the laminin alpha2 chain locus to human chromosome 6q2 in severe
      and mild merosin deficient congenital muscular dystrophy.
AB  - About half of the children with classical congenital muscular dystrophy (CMD)
      show an absence in their skeletal muscle of laminin alpha2 chain, one of the
      components of the extracellular matrix protein, merosin. Linkage analysis
      implicated the laminin alpha2 chain gene (LAMA2) on chromosome 6q2, now confirmed
      by the discovery of mutations in the laminin alpha2 chain gene. We have further
      investigated the location of the LAMA2 locus on chromosome 6q2, using both
      linkage analysis in nine informative families and homozygosity mapping in 13
      consanguineous families. Four of these families only had mild or moderate down
      regulation of laminin alpha2 chain expression and a milder phenotype; the rest
      had no protein or only a trace. Haplotype analysis in all the informative
      families, including those with partial laminin alpha2 expression, was compatible
      with linkage to chromosome 6q2. This observation expands the spectrum of the
      phenotype secondary to laminin alpha2 chain deficiency. Our results suggest that
      the LAMA2 locus is more centromeric than previously proposed. Recombinant events
      place the locus between markers D6S470 and D6S1620 in an interval of less than 3
      cM.

PMID- 9039985
TI  - Identification of a common low density lipoprotein receptor mutation (R329X) in
      the south of England: complete linkage disequilibrium with an allele of
      microsatellite D19S394.
AB  - Familial hypercholesterolaemia is commonly caused by mutations in the low density
      lipoprotein receptor (LDLR) gene and more than 300 different mutations have been
      described worldwide. Some mutations occur at relatively higher frequency in
      certain populations, reflecting both chance and demography, most evident in
      founder populations. As part of a study of kindreds of 78 probands from
      Southampton and south west Hampshire, we identified the same mutation (R329X) in
      9/78 (11.5%) probands. In all (100%) of these probands, length allele 259nt of
      the 17 allele microsatellite D19S394, sited approximately 250 kilobases telomeric
      and 5' to the LDLR gene, was observed, although in the general population this
      allele has a prevalence of only 16.1%. A simple diagnostic assay for R329X was
      constructed in conjunction with more detailed family studies. Both the R329X and
      linked D19S394 allele also cosegregated with the FH phenotype within each
      kindred. Although R329X involves a CpG site, it is highly likely that the
      families are identical by descent for R329X, we surmise with a common ancestor
      within 500 to 1000 years, although the mutation is not restricted to this
      geographical area. This relationship illustrates that the linkage disequilibrium
      of gene LDLR with marker D19S394 will enable rapid recognition using D19S394
      genotype of possible common FH mutation(s) within a cohort of FH patients from a
      particular locality or ethnic group.

PMID- 9039984
TI  - Fucosidosis: genetic and biochemical analysis of eight cases.
AB  - The molecular basis of the deficiency of alpha-L-fucosidase has been investigated
      in eight patients who had been diagnosed clinically and enzymatically as
      suffering from the autosomal recessive lysosomal storage disease fucosidosis.
      None of the patients had a deletion or gross alteration of the alpha-L-fucosidase
      gene (FUCA1). Single strand conformation polymorphism (SSCP) analysis followed by
      direct sequencing of amplified exons and flanking regions identified putative
      disease causing mutations in six of the patients, who had severe forms of the
      disease and very low residual alpha-L-fucosidase activity and protein. They were
      a 10 bp deletion in exon 1 (E113fs), a 1 bp deletion at position -2 of intron 2
      (S216fs), a g-->a transition at IVS5+1, point mutations W183X and N329Y in exons
      3 and 6, respectively, and a compound allele consisting of a point mutation in
      the signal peptide in exon 1, P5R, and a 1 bp insertion in exon 6 (Y330fs). One
      patient in whom an SSCP change was not detected had residual alpha-L-fucosidase
      activity and cross reacting protein in the heterozygous range and normal
      metabolism of metabolites containing fucose in his fibroblasts, consistent with
      the low activity polymorphism. The eighth patient, who had a partial deficiency
      of alpha-L-fucosidase in her fibroblasts and leucocytes at a young age but normal
      alpha-L-fucosidase activity and protein at a later age, was homozygous for the
      common Q281R polymorphism in exon 5. She had no other sequence changes and Kivlin
      (Peters plus) syndrome has subsequently been diagnosed. The basis of her
      transient deficiency of alpha-L-fucosidase is not known. The detection of five
      novel mutations in six severely affected patients confirms the genetic
      heterogeneity in fucosidosis.

PMID- 9039986
TI  - Genetic refinement of dominant optic atrophy (OPA1) locus to within a 2 cM
      interval of chromosome 3q.
AB  - Autosomal dominant optic atrophy (OPA, MIM 165500) is an eye disease
      characterised by variable optic atrophy and reduction in visual acuity. It has an
      insidious onset in the first decade of life and is clinically highly
      heterogeneous. It is associated with a centrocecal scotoma of varying size and
      density and an acquired blue-yellow dyschromatopsia. Recent studies of three
      large Danish pedigrees have mapped a gene for dominant optic atrophy (OPA1) to a
      10 cM region on chromosome 3q, between markers D3S1314 and D3S1265 (3q28-qter).
      Genetic linkage analysis in five British pedigrees confirms mapping to chromosome
      3q28-qter. Haplotype analysis of a seven generation pedigree positions the
      disease causing gene between loci D3S3590 and D3S1305, corresponding to a genetic
      distance of 2 cM. This represents a significant linkage refinement and should
      facilitate positional cloning of the disease gene.

PMID- 9039987
TI  - Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome
      type I.
AB  - This study reports the molecular characterisation of the bilirubin UDP
      glucuronosyl-transferase gene (UGT1) in a group of patients of Sardinian descent
      with Crigler-Najjar syndrome type I and their relatives. Sequence analysis of
      both UGT1A exon 1 and common exons 2-5 was performed in all patients, leading to
      the detection of AF170 and a novel mutation (470insT), both residing in UGT1A
      exon 1. All but two heterozygotes for the AF170 mutation showed normal serum
      bilirubin levels. These two subjects were also heterozygous for the sequence
      variation A(TA)7TAA in the promoter region of the UGT1A gene.

PMID- 9039988
TI  - Pendred syndrome: evidence for genetic homogeneity and further refinement of
      linkage.
AB  - Pendred syndrome is the association between congenital sensorineural deafness and
      goitre. The disorder is characterised by the incomplete discharge of radioiodide
      from a primed thyroid following perchlorate challenge. However, the molecular
      basis of the association between hearing loss and a defect in organification of
      iodide remains unclear. Pendred syndrome is inherited as an autosomal recessive
      trait and has recently been mapped to 7q31 coincident with the non-syndromic
      deafness locus DFNB4. To define the critical linkage interval for Pendred
      syndrome we have studied five kindreds, each with members affected by Pendred
      syndrome. All families support linkage to the chromosome 7 region, defined by the
      microsatellite markers D7S501-D7S523. Detailed haplotype analysis refines the
      Pendred syndrome linkage interval to a region flanked by the marker loci D7S501
      and D7S525, separated by a genetic distance estimated to be 2.5 cM. As potential
      candidate genes have as yet not been mapped to this interval, these data will
      contribute to a positional cloning approach for the identification of the Pendred
      syndrome gene.

PMID- 9039989
TI  - Exclusion of CAG repeat expansion as the cause of disease in autosomal dominant
      retinitis pigmentosa families.
AB  - The involvement of genes with expanded tracts of (CAG)n in some neurodegenerative
      diseases is well established. Whether genes containing these motifs could also
      have a role in degenerative diseases affecting the retina, which is also neural
      in origin, is unknown. We investigated (CAG)n expansions as a cause of disease in
      a panel of eight autosomal dominant retinitis pigmentosa (ADRP) pedigrees,
      including families known to map to the RP9, RP11, and RP13 loci, using the
      technique known as "repeat expansion detection" (RED). An expansion was detected
      in one of the unlinked families, but it did not segregate with the disease and
      was thus nonpathogenic. Expansions were not detected in any other families. In
      conclusion, expanded (CAG)n repeats are not the cause of disease in the families
      we have studied, but given the high level of heterogeneity in RP and in retinal
      degenerations in general they remain strong candidates for involvement in other
      forms of retinal dystrophy.

PMID- 9039990
TI  - Normal erythrocyte membrane Gs alpha bioactivity in two unrelated patients with
      acrodysostosis.
AB  - Shortening of the tubular bones of the hands and feet with cone shaped epiphyses
      is known as peripheral dysostosis and is common to several syndromes including
      acrodysostosis and Albright's hereditary osteodystrophy (AHO). The underlying
      defect in AHO is known to be a reduction in bioactivity of the alpha subunit of
      the signal transducing protein, Gs, and heterozygous deactivating mutations have
      been shown in the Gs alpha gene. Because of additional overlapping clinical and
      radiological features it has been suggested that acrodysostosis and AHO represent
      poles of a single diagnostic spectrum. We have measured Gs alpha bioactivity in
      two unrelated patients with a clinical diagnosis of acrodysostosis and found both
      to be normal. Mutation analysis of the Gs alpha gene showed no sequence variation
      in 12 of the 13 exons examined. These results indicate that, at least in a
      proportion of patients with acrodysostosis, the condition is aetiologically
      distinct from AHO.

PMID- 9039992
TI  - The role and practice of the genetic nurse: report of the AGNC Working Party.
AB  - The role of the genetic nurse has evolved historically with the emergence of
      clinical genetics in the field of health care. During 1994, a Practice Working
      Party was convened by the Genetic Nurses and Social Workers Association in
      response to discussion about the role of the nurse within and between regional
      genetics centres. The Working Party conducted a study of the current nursing
      practice and attitudes of nurses and clinicians to the nursing role, as a basis
      for future discussion and planning for educational needs. This paper describes
      the role of the genetic nurse within the United Kingdom and offers suggestions
      for assessment of competency. Strong themes emerging from respondents' comments
      include the need and desire for multi-professional team work, and it is apparent
      that most respondents felt the families' needs would best be served by a skilful
      combination of medical and nursing input, rather than adherence to traditional
      roles.

PMID- 9039991
TI  - Germline and somatic mosaicism in a female carrier of Hunter disease.
AB  - Carrier detection in a mucopolysaccharidosis type II family (Hunter disease)
      allowed the identification of germline and somatic mosaicism in the patient's
      mother: the R443X mutation was found in a varying proportion in tested tissue (7%
      in leucocytes, lymphocytes, and lymphoblastoid cells, and 22% in fibroblasts).
      The proband's sister carries the at risk allele (determined by haplotype
      analysis), but not the mutation. In sporadic cases of X linked diseases, germline
      mosaicism of the proband's mother is difficult to exclude and should be
      considered in genetic counselling.

PMID- 9039993
TI  - Haemochromatosis: a gene at last?

PMID- 9039994
TI  - Alagille syndrome.
AB  - Alagille syndrome (OMIM 118450) is an autosomal dominant disorder associated with
      abnormalities of the liver, heart, eye, skeleton, and a characteristic facial
      appearance. Also referred to as the Alagille-Watson syndrome, syndromic bile duct
      paucity, and arteriohepatic dysplasia, it is a significant cause of neonatal
      jaundice and cholestasis in older children. In the fully expressed syndrome,
      affected subjects have intrahepatic bile duct paucity and cholestasis, in
      conjunction with cardiac malformations (most frequently peripheral pulmonary
      stenosis), ophthalmological abnormalities (typically of the anterior chamber with
      posterior embryotoxon being the most common), skeletal anomalies (most commonly
      butterfly vertebrae), and characteristic facial appearance. Inheritance is
      autosomal dominant, but expressivity is highly variable. Sibs and parents of
      probands are often found to have mild expression of the presumptive disease gene,
      with abnormalities of only one or two systems. The frequency of new mutations
      appears relatively high, estimated at between 15 and 50%. The disease gene has
      been mapped to chromosome 20 band p12 based on multiple patients described with
      cytogenetic or molecular rearrangements of this region. However, the frequency of
      detectable deletions of 20p12 is low (less than 7%). Progress has been made in
      the molecular definition of an Alagille syndrome critical region within the short
      arm of chromosome 20. We will review the clinical, genetic, cytogenetic, and
      molecular findings in this syndrome.

PMID- 9039995
TI  - Androgen insensitivity with mental retardation: a contiguous gene syndrome?
AB  - We present data to suggest the existence of a mental retardation (MR) locus at
      Xq11.2-q12 between DXS1 and DXS905, identified in two subjects with complete
      androgen insensitivity syndrome (CAIS) and MR. Androgen insensitivity syndrome is
      a disorder of male sexual differentiation caused by a defect in the androgen
      receptor (AR) gene (Xq11-q12). Two subjects with CAIS resulting from a complete
      deletion of the AR gene have previously been reported, one of whom also has MR.
      We have identified another mentally retarded person with a complete deletion of
      the AR gene. The deletion in the two patients with CAIS and MR extends past the
      AR gene and includes several marker loci both proximal and distal to the AR gene,
      the limits of the deletions being DXS1 and DXS905. The deletions in the CAIS
      patients who do not have MR do not include any of the markers outside the AR gene
      itself. These data suggest that located close to the AR gene is a gene which is
      implicated in non-specific MR.

PMID- 9039996
TI  - Functional Xp disomy and de novo t(X;13)(q10;q10) in a girl with hypomelanosis of
      Ito.
AB  - We report on a 16 month old girl with hypomelanosis of Ito and a balanced de novo
      (X;13)(q10;q10) translocation in which the der(Xp13q) had the X centromere (as
      assessed by FISH with the DXZ3 probe). A functional Xp disomy was shown in a
      small proportion of cultured lymphocytes by means of a BrdU terminal pulse. This
      observation supports the notion of a distinct form of hypomelanosis of Ito
      resulting from a functional Xp disomy.

PMID- 9039997
TI  - Familial complex chromosome rearrangement ascertained by in situ hybridisation.
AB  - A complex familial chromosome translocation has been ascertained by combining
      classical cytogenetics and CISS (chromosomal in situ suppression). Cytogenetic
      analysis of a chorionic villus sample with G banding showed a 47,XX,-2,
      +der(2)t(2;22),+der(22)t(2;22) karyotype. Analysis of peripheral blood
      lymphocytes from the parents by G banding and CISS showed a more complex
      translocation in the father: 46,XY,-2,-11,-22, +der(2) t(2;11)(q13;q23), +der(11)
      t(11;22) (q23;q11.2), +der(22) t(2;22) (q13;q11.2). Definitive analysis of
      cultured amniotic fluid cells showed a double partial trisomy of chromosomes 11
      and 22. The couple decided to continue the pregnancy. The fetal karyotype was
      confirmed at birth. Clinical abnormalities present in our patient were typical of
      an unbalanced 11;22 translocation. Our findings confirm that chromosome painting
      techniques allow a better characterisation of complex chromosome rearrangements
      which may be difficult to detect in G banded karyotypes.

PMID- 9039998
TI  - Paternal uniparental disomy for chromosome 6 causes transient neonatal diabetes.
AB  - We report an infant with intrauterine growth retardation and transient neonatal
      diabetes who has paternal uniparental disomy for chromosome 6. The infant was not
      dysmorphic and had no congenital anomalies. To our knowledge, this is the third
      case of paternal uniparental disomy occurring in an infant with transient
      neonatal diabetes, thus confirming the association.

PMID- 9039999
TI  - Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with
      matrilineal aminoglycoside ototoxicity.
AB  - Irreversible hearing loss is a catastrophic complication of treatment with
      aminoglycoside antibiotics such as streptomycin, gentamycin, and kanamycin. Many
      kindreds showing a matrilineal pattern of inheritance of this trait have been
      described in China where the widespread use of aminoglycoside antibiotics
      accounts for approximately 25% of profound deafness in some districts. Because of
      the characteristic inheritance pattern, mitochondrial DNA (mtDNA) mutations were
      postulated to be the cause of the deafness in these pedigrees. In 1993 it was
      shown that an A to G substitution at base pair 1555 of the mitochondrial 12S
      ribosomal RNA gene was the only mutation common to all the families with
      aminoglycoside ototoxicity. We ascertained three Mongolian pedigrees from the
      School for the Deaf and Blind in Ulaanbaatar, all of which contained multiple
      affected subjects with streptomycin induced deafness in a pattern consistent with
      matrilineal transmission. Amplified mtDNA, obtained from transformed
      lymphoblastoid cell lines using previously described primers, showed the A to G
      point mutation in the 12S rRNA gene in two of the three families by restriction
      analysis as well as direct sequencing. No other example of this substitution was
      found among 400 control samples from Mongolians with normal hearing. We have thus
      confirmed the clinical relevance of the 1555 A to G mitochondrial mutation in the
      12S rRNA gene by identifying it in affected subjects with familial aminoglycoside
      ototoxicity in another ethnic group. In countries where aminoglycosides are
      widely used, genetic counselling and screening of high risk families before the
      use of these drugs could have a dramatic effect on the incidence of deafness.

PMID- 9040000
TI  - Parents' responses to predictive genetic testing in their children.

PMID- 9040001
TI  - D409H/D409H genotype in Gaucher-like disease.

PMID- 9040002
TI  - Anti-Fas IgG1 antibodies recognizing the same epitope of Fas/APO-1 mediate
      different biological effects in vitro.
AB  - Fas/APO-1 is a cell surface glycoprotein that mediates programmed cell death or
      apoptosis when cross-linked with agonistic anti-Fas or anti-APO-1 mAb or the
      endogenous Fas/APO-1 ligand. In this report, we examined the in vitro biological
      properties of a panel of anti-human Fas mAb of IgG1 subclass (ZB4, VB3, WB3 and
      CBE). We found that anti-Fas clone VB3 induced marked apoptotic cell death in
      Fas/APO-1-expressing Jurkat cells, although this cell killing was delayed when
      compared to the cytolytic effect mediated by the prototypic anti-Fas antibody of
      IgM subclass (clone CH-11). The ZB4 antibody, on the other hand, efficiently
      blocked apoptosis induced by CH-11. The WB3 and CBE clones neither induced or
      inhibited apoptosis. These antibodies were all found to recognize one and the
      same linear site on the Fas/APO-1 molecule, despite their different biological
      effects. The ability of these anti-Fas mAb to induce or inhibit apoptosis
      appeared to correlate with their relative affinity for the Fas/APO-1 molecule.
      These results provide further evidence for the potential of anti-Fas antibodies
      of the IgG1 subclass to elicit signals via the Fas/APO-1 molecule.

PMID- 9040003
TI  - Serum TABM produced during anterior chamber-associated immune deviation passively
      transfers suppression of delayed-type hypersensitivity to primed mice.
AB  - Injection of soluble protein antigen into the anterior chamber of the eye of
      primed mice induces anterior chamber-associated immune deviation (ACAID) which is
      manifested by suppression of delayed-type hypersensitivity (DTH) to the antigen.
      Recently, we found that ACAID induced in primed mice also results in a rapid rise
      in serum of soluble T lymphocyte-derived proteins specific for nominal antigen
      (TABM). Here, we demonstrate that serum TABM induced in primed mice during ACAID
      will transfer the suppression of DTH to mice primed to the same antigen. Sera
      from TNP-BSA-primed mice that received an anterior chamber injection of TNP-BSA,
      but not BSA alone, suppressed the DTH response to TNP when injected into other
      TNP-BSA-primed mice. Sera absorbed with Sepharose beads conjugated with either
      anti-TCR C(alpha), anti-TCR C(beta), anti-TABM or TNP-BSA did not contain TNP
      specific TABM and did not transfer suppression of DTH. These results suggest that
      the antigen-specific, TCR C(alphabeta)+ TABM that appear in serum during ACAID
      are able to confer on or amplify the capacity of sensitized T cells to suppress
      DTH. We believe this to be the first demonstration of an in vivo immunologic
      function that is specifically associated with TABM produced in vivo.

PMID- 9040004
TI  - Amino acid residues required for binding of vascular cell adhesion molecule-1 to
      integrin alpha 4 beta 7.
AB  - The homologous Ig-like domains 1 and 4 of vascular cell adhesion molecule (VCAM)
      1 present binding sites to the leukocyte integrins alpha 4 beta 1 and alpha 4
      beta 7 . In the present study, amino acid substitution mutants were used to
      identify sequence motifs mediating binding of integrin alpha 4 beta 7 to the
      first domain of VCAM-1. We demonstrate that binding of integrin alpha 4 beta 7 to
      VCAM-1 containing the D40A mutation located in the loop between beta strands C1
      and D1 was completely abrogated and was not restored by activating integrin
      binding functions with Mn2+. Thus, the I(39)DSP motif functions as a central
      recognition site for integrin alpha 4 beta 7. Analysis of the E66A mutation
      demonstrated that the G(64)NEH sequence, which is exposed on the loop structure
      between beta strands E1 and F1, represents an additional recognition site for
      alpha 4 beta 7 integrin. However, the inhibitory effect of the E66A mutation on
      cell binding was not specific for alpha 4 beta 7 but was also observed for
      integrin alpha 4 beta 1. In contrast to the I(39)DSP and G(64)NEH sequences, the
      K(79)LEK motif present in beta strand G1 was involved in binding to alpha 4 beta
      1 but not alpha 4 beta 7. The function of G(64)NEH and K(79)LEK motifs in alpha
      4++-integrin interactions was confirmed by divalent cation titration assays and
      peptide inhibition studies. Integrin binding to E66A or E81A;K82A mutants was
      restored by activation with saturating concentrations of Mn2+. Binding of both
      alpha 4 beta 1 and alpha 4 beta 7 integrins was not affected by E29A, R36A, E50A
      or E87A mutations. Together, these results identify the I(39)DSP and G(64)NEH
      motifs as common recognition sites for both alpha 4 beta 1 and alpha 4 beta 7
      integrins, whereas the K(79)LEK sequence appears to confer specificity for alpha
      4 beta 1 binding.

PMID- 9040005
TI  - Mapping of V beta 11+ helper T cell epitopes on mycobacterial antigen in mouse
      primed with Mycobacterium tuberculosis.
AB  - Antigenic epitopes for Mycobacterium tuberculosis-reactive T cell immune
      responses have been mapped using the purified Mycobacterium protein antigen.
      Lymph node cells from C57BL/6 mice that had been immunized with heat-killed M.
      tuberculosis were cultured with various Mycobacterium protein antigens and their
      reactivity was monitored by proliferative response. Usage of the TCR beta chain
      repertoire was analyzed by flow cytometry. Stimulation of M. tuberculosis-primed
      lymph node cells with MPT59 (antigen 85B, alpha antigen) induced proliferative
      response, production of IL-2 and IFN-gamma, and the expansion of V beta 11+ CD4+
      T cells in conjunction with antigen-presenting cells in an I-Ab-restricted
      manner. Lymph node cells from non-primed mice failed to proliferate in response
      to MPT59. Using peptides covering the complete mature 285 amino acids long MPT59
      protein as 15-mer molecules overlapping by five amino acids, we identified the
      antigenic epitope for MPT59-specific V beta 11+ T cells. The 15-mer peptide,
      covering amino acid residues 240-254 of MPT59 [peptide-25 (amino acids 240-254)],
      contains the motif that is conserved for I-Ab and requires processing by antigen
      presenting cells to trigger peptide-25-specific V beta 11+ CD4+ T cells. We
      conclude from these results that MPT59 and peptide-25 (amino acids 240-254) are
      not superantigens and require antigen processing in order to stimulate V beta 11+
      Th1 cells. This experimental system will provide us with a useful tool for
      delineating the regulation of T cell development in a particular subset of M.
      tuberculosis infection and for developing antigenic peptides for Th1-dominant
      immune responses.

PMID- 9040006
TI  - A new multivalent B cell activation model--anti-IgD bound to Fc gamma RI:
      properties and comparison with CD40L-mediated activation.
AB  - CHO cells permanently transfected with mouse Fc gamma RI alpha chain were
      prepared and used as a model to polyclonally activate murine B cells. The
      transfected CHO cells were treated with mitomycin C and placed into culture with
      varying quantities of anti-IgD. Using this model, murine splenic B cells (from
      BALB/c or C57Bl/6) were activated by mouse IgG2a-anti-IgD (10.4.22 or AF3.33) in
      a manner that is analogous to the activation of B cells seen with highly
      polyvalent anti-IgD (H delta(a)/1) prepared by chemical cross-linking to dextran.
      Efficient B cell activation was seen with nanogram quantities of anti-IgD. In the
      presence of IL-4 and IL-5, IgG1 production levels were equivalent to or better
      than seen when stimulation was with H delta(a)/1-dextran; however, IgE induction
      was not seen in either situation. The Ig production capacity was compared to that
      seen when B cells were activated with CD40L, using either CD40L-transfected CHO
      or a soluble CD40L construct. In the presence of IL-4 and IL-5, once a critical
      threshold of B cells was present, IgE and to a lesser extent IgG1 production was
      inversely proportional to B cell number when CD40L was the activating agent. In
      contrast, with Fc gamma RI-anti-IgD, IgM and IgG1 production was directly
      proportional to B cell number, while IgE production was never seen. Finally, when
      B cells were co-activated with immobilized anti-IgD and CD40L simultaneously, the
      IgE production from B cells induced by CD40L was strongly inhibited, while IgG1
      and IgM production were not affected. Since B cell co-activation via sIg and
      CD40L would be a common scenario in secondary follicles, this inhibition of IgE
      production may be one of the reasons why serum IgE levels are much below IgG in
      normal immune situations.

PMID- 9040007
TI  - A major T cell determinant from the influenza virus hemagglutinin (HA) can be a
      cryptic self peptide in HA transgenic mice.
AB  - Transgenic (Tg) mice expressing the influenza virus PR8 hemagglutinin (PR8 HA)
      were infected with PR8 virus and analyzed for their ability to generate T cell
      responses to individual MHC class II-restricted T cell determinants from the HA.
      HAmemb and HAtrunc mice each express HA transgene mRNA in many tissues (including
      the thymus), but differ in the form and amount of the HA that is expressed:
      HAmemb mice express the entire viral HA as a membrane-bound neo-self antigen,
      whereas HAtrunc mice express lower levels of a truncated HA polypeptide. HAmemb
      mice were found to mediate efficient negative selection of autoreactive T cells
      directed to the major I-Ed-restricted and I-Ad-restricted determinants from the
      HA (designated S1 and S2 respectively). S1-specific T cell responses were
      similarly undetectable in PR8-infected HAtrunc mice. However, S2-specific T cells
      were only partially eliminated in HAtrunc mice; indeed, even though their
      frequency was reduced relative to non-Tg mice, S2-specific T cells still
      constituted a sizable population in PR8-infected HAtrunc mice. Moreover, the S2
      specific T cells from HAtrunc and non-Tg mice appeared to be equally sensitive to
      stimulation with S2 peptide, and in each case utilized highly diverse T cell
      receptors to recognize S2-I-Ad. The findings demonstrate that an individual class
      II-restricted T cell determinant can be recognized as a cryptic self peptide
      during T cell repertoire formation and as an immunodominant peptide in the
      context of an anti-viral T cell response, providing a basis for the induction of
      autoreactive T cells by viruses containing homologs of self antigens.

PMID- 9040009
TI  - Prediction of murine MHC class I epitopes in a major house dust mite allergen and
      induction of T1-type CD8+ T cell responses.
AB  - The group I (Der p 1) allergen of Dermatophagoides pteronyssinus (house dust
      mite, HDM) contains several T helper (Th) epitopes recognized by C57BL/6 mice,
      with the peptide (111-139) containing a dominant MHC class II-restricted epitope
      (113-127). Since CD8+ T cells are thought to play a role in the regulation of
      allergic disease, we examined the Der p 1 sequence for potential MHC class I
      binding motifs and observed that residues 111-119 (FGISNYCQI) contain motifs for
      H-2Db and Kb. Furthermore, immunization of C57BL/6 mice with unadjuvanted Ty
      virus-like particles (VLP) carrying Der p 1 (111-139), a method known to induce
      murine cytotoxic T lymphocyte (CTL) responses, primed Der p 1 (111-119)-specific
      Db-restricted CTL which produce high levels of IFN-gamma and low levels of IL-5
      and IL-6 in vitro (T1-type CTL). VLP carrying the minimal epitope (FGISNYCQI)
      also induced a CTL response following immunization without adjuvant by various
      routes. Der p 1 (111-139)-VLP adjuvanted with alum did not prime CTL in C57BL/6
      mice but were found to prime Th1-type CD4+ T cells that recognize the overlapping
      peptide (113-127) and native protein. The ability to successfully predict
      allergen-specific CD8+ T cell epitopes and prime CD8+ and/or CD4+ T cell
      responses provides an opportunity to dissect the relative roles of these T cells
      in the regulation of allergic responses and may offer therapeutic potential for
      reprogramming Th2-type allergic responses.

PMID- 9040008
TI  - Evidence for heterogeneous TCR V beta repertoire expression in mercury-induced
      immune disorders in rats.
AB  - Administration of subtoxic doses of HgCl2 affects differentially the immune
      system depending on the strain of rats tested. Susceptible Brown-Norway (BN) rats
      exhibit a CD4+ T cell-dependent polyclonal activation of B cells; in contrast,
      Lewis (LEW) rats are resistant and develop an immunosuppression mediated by CD8+
      T cells recruited by CD4+ T cells. The mechanisms by which mercury induces immune
      disorders are poorly understood. We were interested in analyzing the diversity
      and mercury-mediated changes of the TCR Vbeta repertoire in the BN and LEW
      strains of rats at different times of HgCl2 exposure. Our results obtained after
      analysis of lymph node T cells by RNase protection assay, flow cytometry or
      immunoscope assay (i) were not consistent with a superantigen-like stimulus since
      we observed neither a V beta-selective expansion nor deletion that would have
      been expected and (ii) showed that in BN rats, as well as in LEW rats, an
      increase in the number of T cells was associated with the heterogeneous TCR V
      beta repertoire, thus supporting a polyclonal T cell activation. However, in BN
      rats the total number of T cells increased very rapidly, whereas in LEW rats only
      CD8+ T cells accumulated.

PMID- 9040010
TI  - Definition of an extended MHC class II-peptide binding motif for the autoimmune
      disease-associated Lewis rat RT1.BL molecule.
AB  - The Lewis rat, an inbred rat strain susceptible to several well-characterized
      experimental autoimmune diseases, provides a good model to study peptide-mediated
      immunotherapy. Peptide immunotherapy focussing on the modulation of T cell
      responses by interfering with TCR-peptide-MHC complex formation requires the
      elucidation of the molecular basis of TCR-peptide-MHC interactions for an
      efficient design of modulatory peptides. In the Lewis rat most autoimmune
      associated CD4+ T cell responses are MHC class II RT1.BL restricted. In this
      study, the characteristics of RT1.BL-peptide interactions were explored. A series
      of substitution analogs of two Lewis rat T cell epitopes was examined in a direct
      peptide-MHC binding assay on isolated RT1.BL molecules. Furthermore, other
      autoimmune-related as well as non-disease-related T cell epitopes were tested in
      the binding assay. This has led to the definition of an extended RT1.BL-peptide
      binding motif. The RT1.BL-peptide binding motif established in this study is the
      first described rat MHC-peptide binding motif based on direct MHC-peptide binding
      experiments. To predict good or intermediate RT1.BL binding peptides, T cell
      epitope search profiles were deduced from this motif. The motif and search
      profiles will greatly facilitate the prediction of modulatory peptides based on
      autoimmune-associated T cell epitopes and the identification of target structures
      in experimental autoimmune diseases in Lewis rats.

PMID- 9040011
TI  - Targets of p56(lck) activity in immature thymoblasts: stimulation of the
      Ras/Raf/MAPK pathway.
AB  - Previous studies suggest that p56(lck) activity influences thymocyte development
      at a stage prior to TCR alphabeta expression. Transgenic mice that express high
      levels of p56(lck) activity during thymopoiesis develop thymic lymphomas
      consisting of cells with immature surface phenotypes. We have utilized cell lines
      derived from lck-induced thymic tumors to define biochemical pathways regulated
      by p56(lck) activity in immature thymocytes. Here we report that components of
      the Ras/Raf/MAPK pathway are constitutively activated in these lck-transformed
      immature thymoblasts. p56(lck) utilizes Shc and Grb2 adaptors to mediate
      activation of p21(ras) in the thymoblast lines by promoting tyrosine
      phosphorylation of the Shc protein and constitutive interaction between Shc and
      Grb2. The putative guanine nucleotide exchange factor p95(vav) is also maintained
      in constitutively tyrosine phosphorylated form as a result of elevated Lck
      activity. One target of activated Ras, the Raf-1 kinase, is hyperphosphorylated
      and downstream targets of activated Raf-1, Erk1 and Erk2, are hyperphosphorylated
      and activated in Lck-transformed thymocytes. Forskolin treatment reverses Raf-1
      hyperphosphorylation in the cells and inhibits proliferation by blocking G1/S
      transition. In contrast, conventional protein tyrosine kinase inhibitors block
      proliferation by arresting Lck thymoblasts at G2/M. Lck-mediated stimulation of
      the Ras/Raf/MAPK pathway is also required to maintain cell viability by
      preventing programmed cell death. In summary, p56(lck) activity stimulates G1/S
      transition in immature thymoblasts and maintains cell viability via transduction
      of constitutive activation signals downstream to components of the Ras/Raf/MAPK
      pathway.

PMID- 9040012
TI  - In vivo analysis of Fas antigen-mediated apoptosis: effects of agonistic anti
      mouse Fas mAb on thymus, spleen and liver.
AB  - Fas antigen (Fas/CD95) is a cell surface receptor protein that mediates apoptosis
      inducing signals. To analyze the function of Fas in vivo, we examined the effects
      of agonistic anti-Fas antibodies in mice. The i.p. administration of the hamster
      anti-mouse Fas mAb, RK-8, which induced apoptosis both in vivo and in vitro, did
      not kill adult mice, whereas those given the another hamster anti-mouse Fas mAb,
      Jo2, rapidly died of fulminant hepatitis with hemorrhage. Histological analyses
      of mice given RK-8 indicated severe damage of the thymus, and moderate damage of
      the spleen and liver. Most of the thymocytes and some hepatocytes underwent
      apoptosis within 1 day of administration. Flow cytometry revealed that CD4+ T
      cells were more sensitive to Fas-mediated apoptosis than CD8+ T cells. At day 7
      after administration, the thymus was atrophied. These in vivo effects of RK-8
      were transient; the thymus was regenerated, and the liver and spleen were
      apparently normal 1 month after injection. The administration of RK-8 into
      newborn mice caused severe damage of the liver and thymus. Most of the
      hepatocytes died and jaundice was induced. The newborn mice died within 1 week.
      Most hepatocytes of newborn mice may be more sensitive to apoptosis-inducing
      signals through Fas than those of adult mice. These results indicated that
      functional Fas, which introduces the death signal in vivo, is expressed on
      thymocytes, CD4+ splenocytes, and some adult and most newborn mouse hepatocytes.

PMID- 9040013
TI  - A continuous central motif of invariant chain peptides, CLIP, is essential for
      binding to various I-A MHC class II molecules.
AB  - Invariant chain (li) associates with MHC class II molecules and performs a number
      of crucial functions in antigen presentation. A nested set of class II-associated
      li peptides (CLIP) has been isolated, comprising the li sequence between residues
      82 and 107. Recently, X-ray crystallographic analysis has revealed that residues
      87-101 occupy the HLA-DR3 peptide-binding groove. Based on our previous results,
      Lee and McConnell have also proposed a model for the binding of CLIP to various
      mouse I-A molecules in the binding groove. CLIP sequences are able to bind many
      MHC class II molecules but the molecular basis of this promiscuity has not yet
      been resolved. We have shown recently that CLIP binding to I-A class II molecules
      is generally tolerant to side chain substitutions, suggesting that the backbone
      structure of CLIP may provide the features critical for its interaction with
      class II. In pursuit of this, backbone stereochemical disruptions by serial D
      alanine substitutions in CLIP86-104 have been used in competitive binding assays
      to I-A class II molecules. These studies have revealed that the phylogenetically
      conserved central continuous region, CLIP91-99, is intolerant to such
      configurational substitutions. Experiments with truncated and frame-shift
      analogues of CLIP showed that for effective binding to class II, the sequence
      element CLIP90-100 must be incorporated into a peptide of 13 or more residues
      including at least three residues N-terminal to this motif. Additionally, it
      appears that different I-A molecules accommodate CLIP in different binding
      frames. These investigations of the relationship between the structure and
      binding of CLIP analogues lead us to propose that there is a general backbone
      motif of a periodic nature within the CLIP sequence that minimizes deleterious
      contacts and allows promiscuous binding to class II molecules.

PMID- 9040014
TI  - Anti-melanoma cytotoxic T lymphocytes (CTL) recognize numerous antigenic peptides
      having 'self' sequences: autoimmune nature of the anti-melanoma CTL response.
AB  - A line of tumor-infiltrating lymphocytes (660TIL) specifically lysed the
      autologous HLA-A2+ melanoma (660MEL) and also most A2+ melanoma cell lines. We
      immunoprecipitated A2 from a large number (>10(12)) of 660MEL cells, extracted
      naturally processed peptides, fractionated them by HPLC, screened the fractions
      for recognition by 660TIL, and found a single predominant and a minor peak of
      activity. Although too little was recovered of the major 660MEL peptide to
      establish its sequence, HPLC fingerprinting showed that it did not correspond to
      any of the known A2-associated melanoma peptides recognized by T cells, including
      peptides from tyrosinase, MART-1/Melan-A, gp100 and MAGE-3. The major 660MEL
      antigenic peptide appears to be derived from MART-1/Melan-A but is neither
      AAGIGILTV nor ILTVILGVL nor any other MART-1/Melan-A peptide containing the A2
      consensus motif. The multiplicity of melanoma peptides recognized by CD8+ T
      cells, most of which are non-mutated (including most likely the present 660MEL
      peptide), suggests the existence of unknown mechanisms, perhaps similar to those
      operating in autoimmune disorders, whereby T cells that recognize normal 'self'
      sequences become activated.

PMID- 9040015
TI  - A wide spectrum of collagen vascular and autoimmune diseases in transgenic rats
      carrying the env-pX gene of human T lymphocyte virus type I.
AB  - To investigate the pathogenesis of human T lymphocyte virus type I (HTLV-I)-
      related diseases, the env-pX gene of HTLV-I was introduced into the germline of
      inbred Wistar-King-Aptekman-Hokudai rats. A wide spectrum of collagen vascular
      diseases was evident in the transgenic rats, including chronic destructive
      arthritis similar to rheumatoid arthritis, necrotizing arteritis mimicking
      polyarteritis nodosa, polymyositis, myocarditis, dermatitis, and chronic
      sialoadenitis and dacryoadenitis resembling Sjogren's syndrome in humans. Thymic
      atrophy with the depletion of CD4 and CD8 double-positive thymocytes was also
      observed. In these animals, a number of autoantibodies, including high titers of
      rheumatoid factor, were present in the serum. We propose that the HTLV-I env-pX
      gene region may play a pathogenetic role in the development of collagen vascular
      and autoimmune diseases associated with autoimmune phenomenon.

PMID- 9040016
TI  - Oxidation products of nitric oxide, NO2 and NO3, in plasma after experimental
      myocardial infarction.
AB  - Nitrite and nitrate (NO2 and NO3), the oxidative products of nitric oxide (NO),
      were elevated in the plasma of rabbits on the third day following ligation of a
      coronary artery. This elevation coincided with increased activity of the
      inducible form of nitric oxide synthase (iNOS) in infarcted heart muscle. Data
      are reported which relate the elevated plasma concentrations of NO2+NO3 (NO(x))
      to the increased induction of iNOS in an infarcted heart. NO2 and NO3 in plasma
      were measured by chemiluminescence. Nitrate was converted to nitrite by nitrate
      reductase. Plasma from the ear vein, right and left ventricle, and coronary sinus
      were analyzed for NO(x), and iNOS activity was enzymatically determined in
      infarcted, risk, and normal areas of the heart. The production equivalent of
      NO(x) by the heart and lung was also calculated. In addition, the effect of a
      specific inhibitor of iNOS, S-methylisothiourea sulfate (SMT) on plasma
      concentration and myocardial production of NO(x) was determined. It was concluded
      that the elevation of plasma NO(x) following onset of myocardial ischemia was
      directly related to increased induction of iNOS in the heart. This conclusion was
      based on a proportional and simultaneous increase in NO(x) plasma concentration
      with myocardial iNOS activation. The inhibitory effect of SMT furnished
      additional confirmation of the relationship between myocardial iNOS activation
      and NO(x) plasma levels in experimental myocardial infarction.

PMID- 9040017
TI  - Optical methods to evaluate the contractile function of unloaded isolated cardiac
      myocytes.
AB  - The enzymatically isolated cardiac myocyte has achieved prominence as an
      experimental model of myocardial excitation contraction coupling. Considerable
      effort has been directed to investigating the shortening behaviour of unattached
      and externally unloaded contracting cardiomyocytes - measured both at the level
      of the whole cell and at the level of the sarcomere. The purpose of this review
      is to provide a survey of these methodological approaches and to identify the
      crucial optical issues involved in striation imaging and whole-cell end-detection
      procedures. Factors limiting the precision with which measurements of
      cardiomyocyte shortening can be made, and sources of error attributable to
      unfavourable optical conditions and myocyte geometry are discussed. Original data
      are presented, examining the relationship between sarcomere and whole-cell
      shortening dynamics recorded simultaneously in the same cells. These results
      confirm that the measurement of cell length can provide an adequate index of
      sarcomere dynamics if the data are obtained under carefully controlled conditions
      where the entire cell is monitored to ensure minimal geometric or optical non
      linearities. The role of the myocyte's internal load in modulating the observed
      contractile responses at differing levels of inotropic status is discussed.
      Finally, the validity of interpreting the shortening response of an untethered
      isolated cardiomyocyte as an index of myocardial contractility, reflecting the
      inotropic status, is considered.

PMID- 9040018
TI  - Expression of sense and naturally occurring antisense mRNA of myosin heavy chain
      in rat heart tissue and cultivated cardiomyocytes.
AB  - We investigated the expression of sense- as well as naturally occurring antisense
      mRNA of myosin heavy chains (MHC) in rat cardiomyocytes during development and
      cultivation. Relative distribution of the two MHC mRNA isoforms (alpha and beta)
      was studied by quantitative polymerase chain reaction. Primers were specific for
      the 3' untranslated region of alpha- and beta-MHC. Sense-alpha-MHC mRNA increased
      from 0% in the fetal heart to 45 +/- 8% in neonatal and to 75 +/- 5% in adult rat
      myocardium. In neonatal heart cell culture (10% bovine calf serum), alpha-MHC
      mRNA levels changed from 49 +/- 3% (day 0 = fresh isolated cells) to 61 +/- 6%
      (day 5 of cultivation). alpha-MHC mRNA of cultivated adult cardiomyocytes (serum
      free) decreased from 90 +/- 7% (day 0) to 30 +/- 5% (day 5). Antisense-mRNA of
      both alpha- and beta-MHC was detected in rat cardiac tissue and cultivated
      cardiomyocytes. The expression of antisense-MHC mRNA did not change during
      development and cultivation. Antisense-alpha-MHC mRNA was the abundant isoform
      and was half of sense-alpha-MHC mRNA.

PMID- 9040019
TI  - Electrophysiological effects of vasoactive intestinal peptide in rabbit atrium: a
      modulation of acetylcholine activity.
AB  - Vasoactive Intestinal Peptide (VIP) is a 28-amino acid peptide partially co
      secreted with acetylcholine (Ach) in the atrial tissue. We studied the
      electrophysiological effects of VIP and Ach in rabbit isolated right atrium by
      the microelectrode technique. After a 10-min superfusion with VIP, action
      potential duration at 90% of repolarization (APD90) was lengthened by 23% (P =
      0.01) at the concentration of 10(-8) M (n = 10), by 22% (P = 0.004) at 10(-7) M
      (n = 10) and by 33% (P = 0.03) at 2 x 10(-7) M (n = 5). To explain this APD90
      lengthening, we performed 10 other experiments with VIP 10(-7) M, including five
      preparations pretreated with verapamil (10(-6) M) for 20 min. In the five
      preparations not pretreated, APD90 was increased by 27% (P = 0.04) after 10 min
      but remained unchanged in those previously exposed to verapamil, suggesting that
      VIP is a calcium current activator. Ach (1.4 x 10(-5) M) was superfused in five
      other experiments and we observed a 31% decrease in APD90 (P= 0.04) at 10 min.
      After washout, we simultaneously perfused, on the same preparations, Ach (same
      concentration) and VIP (10(-7) M) for 10 min. The decrease in APD90 (19%) was no
      longer significant. VIP (2 x 10(-7) M) lengthened cellular effective refractory
      periods (ERP) by 26% (P = 0.04) after 10 min (n = 5), whereas Ach (1.4 x 10(-5)
      M) decreased ERP by 33% (P = 0.04) at 10 min (n = 5). In conclusion, VIP
      lengthens atrial APD90, which may be the result of calcium current activation. In
      addition, VIP could modulate Ach activity in limiting APD90 shortening in the
      presence of Ach and because of its opposite effect on atrial ERP. Therefore, VIP
      could be involved in the control of vagal atrial arrhythmias.

PMID- 9040020
TI  - Altered cardiac mechanism and sarcoplasmic reticulum function in pressure
      overload-induced cardiac hypertrophy in rats.
AB  - Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in
      the regulation of intracellular Ca2+. Its functional properties are central to
      the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we
      examined the hypothesis that alterations in SR function occur during the
      development of hypertrophy of the left ventricle (LV) induced in rats by pressure
      overload secondary to abdominal aortic coarctation. Ten days, 4 and 8 weeks after
      the operation, hemodynamic parameters were measured using a catheter-tip
      manometer. The SR vesicles of hypertrophic LV (group A) and sham-operated LV
      (group S) at each stage were used to study Ca2+ release and uptake, and to
      characterize the ryanodine receptor. Moderate hypertrophy was observed in group A
      even at the earliest stage. Systolic LV pressure and peak +dP/dt were
      significantly increased in group A. There were no significant change in diastolic
      LV pressure in either group at any stage. Hemodynamic data indicated that LV
      function in group A was enhanced during the development of the hypertrophy. The
      amount of Ca2+ release and uptake, and the number of ryanodine binding sites on
      the SR were higher in group A than in group S at both early and middle stages.
      However, 8 weeks after the operation, SR activity was normal, even though cardiac
      function was still augmented. Our results indicated that LV hypertrophy induced
      by pressure overload is associated with altered intracellular Ca2+ regulation, as
      reflected by the increased Ca2+ release and uptake functions of the SR and the
      quantitative change in the number of ryanodine receptors during the early stages
      of the development of hypertrophy. Therefore, alterations in the SR Ca2+
      transport capacity could account, at least in part, for the alterations in E-C
      coupling seen in hypertrophy.

PMID- 9040021
TI  - Reduced basal NO-mediated dilation and decreased endothelial NO-synthase
      expression in coronary vessels of spontaneously hypertensive rats.
AB  - Basal vasomotor tone in coronary vessels is, in part, maintained by nitric oxide
      (NO) production by endothelial constitutive NO synthase (ecNOS). Alteration of
      coronary circulation observed in left ventricular hypertrophy secondary to
      hypertension could be associated with a decrease in NO production. The aim of
      this study was to measure: (1) coronary flow in the Langendorff-perfused heart
      model at baseline, after maximum vasodilation in response to adenosine (10(-5)
      M), after endothelium-dependent vasodilation in response to bradykinin (10(-8) M)
      and after ecNOS inhibition by nitro-L-arginine methyl ester (L-NAME) (10(-4) M);
      (2) medial thickening of coronary microvessels and perivascular collagen on
      histological heart sections; and (3) ecNOS expression by immunohistochemical
      staining in these vessels using 20-week-old spontaneously hypertensive (SHR) and
      Wistar-Kyoto control rats (WKY). These measurements were determined by computer
      directed color analysis. When SHR were compared with WKY rats, we found: (1) a
      decrease in basal flow (10.1+/-0.6 v 15.3+/-1.2 ml/min/g, n=10, P<0.0001), in
      maximum flow (15.4+/-0.7 v 24.3+/-1.3 ml/min/g, n=10, P<0.001), in bradykinin
      induced flow increment (1.5+/-0.3 v 2.6+/-0.3 ml/min/g, n=5, P<0.05) and in L
      NAME-sensitive flow (3.3+/-0.6 v 6.3+/-0.9 ml/min/g, n=7, P<0.05); (2) an
      increase in medial thickness (9.4+/-0.6 v 5.4+/-0.3 microm, n=8, P<0.001) and in
      perivascular collagen area (1509+/-311 v 462+/-120 microm2, n=8, P<0.01) of
      coronary arterioles; and (3) a decrease in ecNOS expression in the endothelium
      (ecNOS-stained cross-sectional area in arterioles: 40.0+/-9.1 v 84.6+/-9.0
      microm2, n=7, P<O.005). These results suggest that in SHR the decrease in basal
      coronary flow can be related to a structural alteration of the microvessels with
      an increase of perivascular collagen but also to a decrease in ecNOS expression
      which might be associated with reduced NO production.

PMID- 9040022
TI  - Prolongation of murine cardiac allograft survival with vesnarinone.
AB  - Vesnarinone is a non-glycoside positive inotropic drug that has immunomodulating
      actions. In the present study, the effects of vesnarinone on both cardiac
      allografts and lymphocytes were investigated. First, in a mouse model of primary
      vascularized heterotopic cardiac transplantation, the oral vesnarinone treatment
      at a dose of 50 mg/kg/day prolonged median graft survival time significantly as
      compared with the vehicle-treated control. Histopathological examination revealed
      that cellular infiltration and interstitial edema were less prominent in the
      vesnarinone-treated than in the vehicle-treated allografts. The plasma
      concentrations of vesnarinone in mice treated with a single dose of 50 mg/kg were
      within the range of clinical relevance. To clarify the mechanism of action, in
      vitro studies were performed. The generation of specific cytotoxic T lymphocytes
      in mixed lymphocyte culture was significantly suppressed by the treatment with
      vesnarinone, especially at 3 and 10 microg/ml. The production of interferon-gamma
      in the co-culture was also suppressed by 10 microg/ml vesnarinone. However, the
      level of cyclic adenosine monophosphate was not significantly affected by
      vesnarinone at 10 microg/ml. The results suggest that vesnarinone acts
      beneficially on rejecting cardiac allografts through its lymphocyte-suppressive
      property, although this property may not be closely associated with the
      inhibiting action of the drug on the cyclic adenosine monophosphate
      phosphodiesterase enzyme.

PMID- 9040023
TI  - Autoantibodies in sera of patients with myocarditis: characterization of the
      corresponding proteins by isoelectric focusing and N-terminal sequence analysis.
AB  - In myocarditis an antigen-specific immune response to cardiac epitopes has been
      demonstrated by several investigators. In 54 patients with histologically proven
      myocarditis, autoantibodies to cardiac tissue were observed in 73% of patients
      utilizing the indirect immunofluorescence test with human myocardium and adult
      heterologous cardiocytes. By immunoblot, 44% of sera from patients reacted with
      cardiac tissue. These antibodies were directed preferentially against proteins
      with the molecular weight of 43 up to 67 kDa. Three particular proteins were
      identified by the use of two-dimensional immunoblot and further characterized by
      amino acid sequence analysis. To characterize the epitopes recognized by the
      autoantibodies isoelectric focusing followed by SDS-PAGE was used to separate the
      complex mixture of proteins from human heart. Immunoblot analysis of antigens
      revealed proteins ranging from a size of 30-67 kDa at isoelectric points of 6.5
      8.5 to be of particular interest. Five of these proteins have now been analyzed
      by N-terminal amino acid sequencing (Edman degradation). One was found to be
      creatine kinase and one was identified as a yet unknown protein. Three proteins
      were N-terminally blocked and were investigated further by enzymatical digestion,
      followed by separation of the usually complex peptide mixtures on HPLC. One of
      the peptides was found to be dihydrolipoamide dehydrogenase, a membrane enzyme,
      and one was identified as a sarcomere specific creatine kinase. Because these
      proteins are intracullularly located enzymes, their pathogenetic role as antigens
      for the autoantibodies remains to be elucidated further.

PMID- 9040024
TI  - The role of the Na+ channel in the accumulation of intracellular Na+ during
      myocardial ischemia: consequences for post-ischemic recovery.
AB  - To further elucidate the role of the Na+ channel in the ischemic accumulation of
      intracellular Na+ (Na+i), 200 microM lidocaine was included in the perfusate for
      5 min prior to 30 min of ischemia in isolated rat hearts paced at 5 Hz. Na+i and
      high-energy phosphates were measured, using 23Na-NMR with the shift reagent
      TmDOTP5- and 31P-NMR, respectively. Control values of phosphocreatine (PCr) and
      ATP were 14.1 +/- 1.5 mM and 7.7 +/- 0.7 mM, respectively (all data: mean +/-
      S.D.). During lidocaine perfusion the rate pressure product (RPP) decreased by
      approximately 50% and Na+i declined from 11.5 +/- 1.5 mM to 9.8 +/- 2.1 mM.
      During ischemia Na+i in lidocaine hearts rose to 17.9 +/- 2.5 mM v 28.4 +/- 1.7
      mM in control hearts (P<0.05). In hearts in which extracellular Ca2+ was lowered
      prior to ischemia to reach a similar RPP decrease as in lidocaine hearts, Na+i
      rose to 26.3 +/- 3.0 mM during ischemia (P<0.05 v lidocaine, N.S. v control).
      Lidocaine did not affect the decline of PCr during ischemia (to 0.5 +/- 0.5 v 0.7
      +/- 0.8 mM in lidocaine and control hearts, respectively) but significantly
      attenuated the initial decrease of pH(i) (6.06 +/- 0.07 v 5.76 +/- 0.04 after 20
      min, P<0.01), attenuated the initial decline of ATP (3.3 +/- 1.3 v 1.5 +/- 0.9 mM
      after 20 min, P<0.05) and delayed the time to onset of contracture. However, at
      the end of ischemia pH(i) (5.73 +/- 0.04 and 5.78 +/- 0.05) and ATP (1.2 +/- 0.6
      and 0.9 +/- 0.8 mM) were not significantly different. At 30 min of reperfusion
      Na+i was 14.9 +/- 2.6 mM in lidocaine hearts v 20.0 +/- 3.1 mM in controls. PCr
      (9.6 +/- 2.3 v 4.9 +/- 0.9 mM, P<0.05) and ATP (3.0 +/- 0.6 v 1.8 +/- 0.6 mM)
      recovered better in lidocaine hearts. Furthermore, developed and end-diastolic
      pressure recovered better in lidocaine hearts. In conclusion, Na+ influx during
      ischemia occurs, at least partly, via the Na+ channels, and blocking this channel
      during ischemia improves post-ischemic functional and metabolic recovery.

PMID- 9040025
TI  - Magnesium-deficiency-enhanced post-ischemic myocardial injury is reduced by
      substance P receptor blockade.
AB  - Dietary Mg-deficiency increases the susceptibility of rat hearts to ischemia
      reperfusion (I-R) injury in vitro, and also promotes substance P-associated
      neurogenic inflammation in vivo. The relationship between Mg-deficiency-induced
      neurogenic inflammation and the subsequently-enhanced free radical-mediated
      oxidative and functional injury during I-R was examined using the substance P
      receptor antagonist, L-703,606. Rats maintained on 3-week Mg-deficient (MgD; <1.8
      mmol Mg/kg food) or Mg-sufficient (MgS; 25 mmol Mg/kg) diets were treated during
      this time with either L-703,606 (1.0 or 3.5 mg/sustained-release pellet, s.c.) or
      a placebo, prior to isolated perfused I-R. Post-ischemic functional recovery
      (pressure-volume work), myocardial effluent lactate dehydrogenase (LDH) activity,
      and lipid hydroperoxides (LOOH) were assessed after 30-min global ischemia. Lipid
      peroxidation-derived free radical production was monitored by alpha-phenyl-N-t
      butylnitrone (PBN) spin trap infusion (2-3 mM final) and toluene-extracted
      effluents were analyzed by electron spin resonance (ESR) spectroscopy.
      PBN/alkoxyl adducts (alpha(H) = 1.89-1.93 G, alpha(N) = 13.58-13.63 G) were the
      dominant ESR signals detected in MgS and MgD I-R hearts; however, MgD hearts
      exhibited greater total LOOH (2.9 x higher) and alkoxyl adduct production (2.3 x
      higher), higher tissue LDH release (1.8 x ) and lower functional recovery (51%
      less) than MgS hearts. MgD rats treated with L-703,606 displayed a dose-dependent
      improvement in myocardial functional recovery (1.5-2 x higher), and reductions in
      LDH release (42-59% lower), total LOOH content (36-73% lower) and alkoxyl
      production (40-65% lower). Interestingly. L-703,606 treatment did not reduce
      functional impairment or lessen the tissue and oxidative injury experienced by
      MgS I-R hearts. These findings suggest that L-703,606 reduced oxidative injury
      and improved functional recovery of MgD I-R hearts by retarding substance P
      mediated inflammatory/pro-oxidant events during the in vivo development of Mg
      deficiency.

PMID- 9040026
TI  - Upregulation of alpha1A- and alpha1B-adrenergic receptor mRNAs in the heart of
      cardiomyopathic hamsters.
AB  - An increased density of alpha1-adrenergic receptors (AR) has been linked to the
      development of necrotic lesions in the heart of hamsters with hereditary
      cardiomyopathy. To determine whether this increase results from an upregulation
      of the receptor mRNA(s), Northern blot analyses were carried out in the heart of
      60-day-old control and cardiomyopathic hamsters using selective DNA probes for
      the three subtypes of alpha1-ARs (alpha1A, alpha1B and alpha1D). Transcripts for
      the three alpha1-ARs were detected in both control and cardiomyopathic hamsters.
      A two-fold increase in the alpha1A- and alpha1B-AR mRNA levels was observed in
      the cardiomyopathic hearts when compared to controls. In contrast, no change in
      the alpha1D-AR mRNA level could be detected. The enhancement in alpha1A- and
      alpha1B-AR mRNA levels was paralleled by a 20% increase in the total number of
      alpha1-ARs, as assessed by [3H]prazosin radioligand binding assays. Competition
      binding assays using subtype selective ligands indicated that the increased
      density of both alpha1A and alpha1B receptors contributes to the total alpha1-AR
      upregulation. Taken together, these data suggest that the early development of
      hereditary cardiomyopathy in hamsters is accompanied by a specific overexpression
      of the alpha1A- and alpha1B-ARs. A discrete increase of the alpha1-AR density
      could contribute to eliciting coronary microspasms, therefore participating in
      the development of focal necrotic lesions that are characteristic of the hamster
      cardiomyopathic model.

PMID- 9040027
TI  - Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy?
AB  - Hereditary hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease,
      but the genetic defects are still unclear in many cases. Reduced myocardial long
      chain fatty acid (LCFA) uptake has been demonstrated in patients with some types
      of HCM. In addition, a possible relationship between a shift ofmyocardial
      substrate utilization and cardiac hypertrophy has been suggested by experimental
      studies. Myocardial uptake of LCFAs occurs via a specific transporter, which is
      homologous with human CD36. CD36 deficiency has also been reported in some
      individuals, and is transmitted as an autosomal dominant trait like HCM. In this
      study, we analyzed CD36 in 47 patients with HCM [29 with asymmetric septal
      hypertrophy (ASH) and 18 without ASH], 11 patients with dilated cardiomyopathy
      (DCM), and 26 patients with pressure-overload cardiac hypertrophy. Eleven
      patients (37.9%) who had HCM with ASH, one (9.1%) with DCM, and two (7.7%) with
      pressure-overload hypertrophy showed CD36 deficiency, while none of the HCM
      patients without ASH had CD36 deficiency. One patient who had HCM with ASH and
      CD36 deficiency showed no myocardial LCFA uptake, although myocardial perfusion
      was normal. Reduced myocardial LCFA uptake despite normal myocardial perfusion
      was demonstrated in the other HCM patients with ASH and CD36 deficiency. Based on
      the high prevalence of CD36 deficiency in HCM patients with ASH, we hypothesize
      that this deficiency might be one etiology of hereditary HCM.

PMID- 9040028
TI  - Selective blockade of AT1 angiotensin II receptors abolishes ischemic
      preconditioning in isolated rabbit hearts.
AB  - The aim of the present study was to assess the participation of angiotensin II
      receptors in the triggering mechanism of ischemic preconditioning. Isolated
      buffer-perfused rabbit hearts were subjected to 40 min of regional ischemia (37
      degrees C) followed by 60 min of reperfusion. Ischemic preconditioning was
      induced with three cycles of 5-min ischemia and 10-min reperfusion given prior to
      the 40-min ischemic period. Infarct size and ventricular function were assessed.
      Ischemic preconditioning reduced infarct size to 5.2 +/- 1.2% of the area at risk
      (mean +/- S.E.M., P<0.001) when compared to controls (26.4 +/- 3.0%), but did not
      protect against ventricular dysfunction. Activation of angiotensin II receptors
      with angiotensin II (100 nM) also limited infarct size (9.6 +/- 2.2%, P<O.01 v
      control group). Inhibition of angiotensin II receptors with [Sar1, Val5, Ala8]
      angiotensin II (saralasin, 1 microM) blocked the protection of ischemic
      preconditioning against necrosis (29.7 +/- 3.2%) while it did not increase
      infarct size in saralasin-treated control hearts (31.5 +/- 3.9%). Furthermore,
      inhibition of the AT1 subtype of the angiotensin II receptor with losartan (20
      microM), but not inhibition of the AT2 subtype with PD-123,319 ditrifluoroacetate
      (10 microM), abolished the infarct size-limiting effect of ischemic
      preconditioning. We conclude that the AT1 angiotensin II receptor participates in
      ischemic preconditioning. Thus, in the isolated rabbit heart, activation of AT1
      receptors must occur before prolonged ischemia for ischemic preconditioning to
      limit infarction.

PMID- 9040029
TI  - Developmental regulation of angiotensin type 1 and 2 receptor gene expression and
      heart growth.
AB  - Little is known regarding the developmental regulation of the cardiac angiotensin
      type 1 (AT1) and type 2 (AT2) receptor genes or their role in normal cardiac
      growth. Regulation of AT1 and AT2 receptor genes were examined using total and
      poly A + RNA isolated from whole Sprague-Dawley rat hearts. AT1 mRNA levels were
      3.5-fold higher in the 19-day-old fetal heart compared to the 90-day-old adult as
      detected with 2 or 5 microg of poly A + RNA. AT2 mRNA was only detectable with 20
      microg of poly A + RNA. AT2 mRNA levels were highest in the 19-day-old fetal
      heart with no detectable message in the 90-day-old adult heart. Qualitative PCR
      for AT2 mRNA also could not detect AT2 mRNA in the adult heart. Treatment with
      the AT1 receptor antagonist losartan for 3 weeks in the 21-day-old rat or for 4
      days in the 38-day-old rat resulted in a significant decrease in heart/body
      weight in both groups and body weight in the 3-week treatment group. AT2 blockade
      for 4 days with PD123319 or beta-receptor blockade with propranolol for 3 weeks
      did not alter heart/body weights. Losartan treatment also resulted in a three
      fold increase in cardiac AT1 mRNA levels in both the 4-day and 3-week treatment
      groups compared to controls. We conclude that Ang II, acting primarily, if not
      exclusively via the AT1 receptor plays a significant role in the regulation of
      normal cardiac growth in the young rat.

PMID- 9040030
TI  - Proliferation of myocardial peroxisomes caused by several agents and conditions.
AB  - In view of considerable gaps in our knowledge of myocardial peroxisomes. the aim
      of the present study is, on the basis of extensive electron-microscopic
      investigations, to provide reliable results on the inducibility of a
      proliferation (increase in the number) of these organelles in rodents' heart by
      several agents and conditions. As far as possible, we compared the response of
      heart and liver peroxisomes. Morphometric investigations were performed to assess
      the effectiveness of the hypolipidemic agent HL 41, erucic acid, ethanol,
      nifedipine, chlorpromazine, two cardiotonic drugs, isoprenaline, adriamycin, and
      physical exercise. The study also included spontaneously hypertensive rats (SHR).
      A further objective was to determine synergistic or additive effects that might
      occur when two or three peroxisome-proliferating stimuli act simultaneously. In
      every case we observed a clear peroxisome proliferation, which was found to
      increase by between 10 and 97% under the influence of an additional inducer. The
      observed increase in peroxisome number ranged from almost 200% to nearly 400%.
      Our results suggest that very different agents and conditions can induce
      myocardial peroxisome proliferation when they lead to metabolic alterations
      associated with an increased need for a peroxisomal beta-oxidation of fatty acids
      as an energy source and/or for preventing toxic effects. Regulatory mechanisms of
      these adaptive processes are apparently also present in the heart via peroxisome
      proliferator-activated receptors (PPARs) and their activation by fatty acids,
      which can also stimulate the PPARs gene expression. The assumption that
      stimulated catalase gene expression might be responsible for the induction of
      peroxisome proliferation as a cellular response to an extraperoxisomal oxidative
      stress situation (isoprenaline, adriamycin, or physical exercise) poses some
      critical questions. These questions pertain especially to: (a) quantitative
      aspects with regard to the possible effectiveness of an increase in catalase
      activity by two-, three-, or four-fold enhanced peroxisome numbers; (b) the role
      of cytoplasmic catalase; (c) the existence and importance of a myocardial
      mitochondrial catalase; and (d) the co-operation between the two H2O2-destroying
      enzymes catalase and glutathione peroxidase.

PMID- 9040031
TI  - Facilitative interactions between noradrenergic and purinergic signaling during
      preconditioning of the rat heart.
AB  - Recent developments in cardiac physiology have focused on the mechanisms
      underlying preconditioning against ischemia-reperfusion injury. Sensing,
      transduction and cardioadaptation to the initial stimulus suggests species
      specific differences in strategy. We and others have found that ischemic stress
      can trigger catecholamine (alpha1-adrenoreceptor)-dependent mechanisms of
      preconditioning. However, in rabbits and dogs, adenosine receptor mechanisms
      appear to predominate. In contrast, the role of the adenosine receptors in rat
      remains controversial. Anticipating a minor role for this metabolite, we examined
      its ability to induce protection in rat heart against a modest ischemic injury
      and also its relationship to the noradrenergic alpha1 pathway. Although redundant
      pathways for inducing adaptation to stress are possible, single transient
      ischemic stress surprisingly utilizes both alpha1-adrenoreceptors and adenosine
      P1 receptors in obligate roles. Thus blockade of either purinergic P1 or alpha1
      adrenergic receptors abolished functional protection induced by single transient
      ischemic stimulus. Selective noradrenergic alpha1-adrenoreceptor stimulation was
      sufficient to protect cardiac recovery after modest ischemic injury, and was
      unaffected by purinergic blockades, suggesting that this is the primary stress
      adaptation pathway for rat. However, exogenous purinergic P1 stimulated
      protection was abolished in either reserpine pretreated, or alpha1-adrenoreceptor
      blockaded hearts. Therefore the cardioadaptive ischemic preconditioning
      mechanisms in rat may involve facilitative modulation of a primary pathway rather
      than redundancy.

PMID- 9040032
TI  - Adenosine preconditioning of human myocardium is dependent upon the ATP-sensitive
      K+ channel.
AB  - Evidence supports the involvement of adenosine receptor stimulation and
      activation of K(ATP) channels in ischemic preconditioning of human myocardium. It
      is unknown, however, whether protection mediated by adenosine receptors is
      dependent upon the K(ATP) channel in the human heart. The purpose of this study
      was to determine whether adenosine-mediated protection against a simulated
      ischemia-reperfusion injury in human myocardium is dependent upon K(ATP)
      channels. Isolated human right atrial trabeculae were placed in tissue baths at
      37 degrees C, oxygenated with a modified Tyrode solution, and field stimulated at
      1 Hz. Trabeculae were subjected to 45 min of normothermic simulated ischemia
      (hypoxic, substrate-free buffer with pacing at 3 Hz.) and 60 min of reperfusion
      (I/R trabeculae). Trabeculae were preconditioned with simulated ischemia (IPC
      trabeculae) or adenosine receptor stimulation (adenosine, 125 micromol/l) for 5
      min (ADO trabeculae) prior to simulated ischemic-reperfusion injury. Inhibition
      of the K(ATP) channel with glibenclamide (10 micromol/l) was combined with
      adenosine pretreatment (ADO+GLI trabeculae) or alone (GLI trabeculae) prior to
      simulated ischemic-reperfusion injury. Developed force (DF) at end reperfusion
      (mean+/-S.E.) was compared to baseline developed force, and tissue creatine
      kinase (CK) activity at end reperfusion was measured. I/R trabeculae showed 27+/
      2% of baseline DF, whereas IPC trabeculae or ADO trabeculae showed 50+/-4% and
      43+/-3% of baseline DF, respectively. ADO+GLI trabeculae showed 25+/-2% and GLI
      trabeculae showed 23+/-4% of baseline DF. Tissue CK activity was enhanced in the
      IPC and ADO trabeculae (433+/-63 U/g wet myocardium, and 415+/-28 U/g wet
      myocardium, respectively). I/R trabeculae had 196+/-26 U/g wet myocardium and
      ADO+GLI trabeculae had 277+/-38 U/g wet myocardium at end reperfusion. The
      results suggest that ischemic preconditioning and adenosine receptor stimulation
      confer functional protection against simulated ischemic-reperfusion, and
      adenosine mediated protection is eliminated by K(ATP) channel inhibition in human
      myocardium.

PMID- 9040033
TI  - [3H]dofetilide binding to cardiac myocytes: modulation by extracellular
      potassium.
AB  - The radioligand [3H]dofetilide binds specifically to the delayed rectifier
      potassium channel and provides a biochemical approach to study interactions of
      Class III drugs with this channel. However, previous studies have examined the
      binding of [3H]dofetilide to cardiac myocytes only at extracellular potassium of
      135 mM. Because previous electrophysiological studies have shown that
      hyperkalemia could alter the pharmacological responses to I(Kr) channel blockers,
      the hypothesis tested in this study was that changing ionic conditions would
      alter characteristics of [3H]dofetilide binding. RESULTS: under physiological
      conditions (Na+ 135 mM, K+ 5 mM), [3H]dofetilide bound to two sites on guinea-pig
      ventricular myocytes (a high-affinity site, K(d) 26+/-8 nM, B(max) 81+/-12
      fmol/10(6) cells: and a low-affinity site, K(d) 1.6+/-0.8 microM, B(max) 1003+/
      173 fmol/10(6) cells, n=11). Binding properties were not altered by changes in
      osmolarity or extracellular sodium. However, when extracellular K+ was increased
      to 20 mM, a single binding site was observed with an affinity K(d) of 120+12 nM
      and a B(max) of 303+/-57 fmol/10(6) cells (P<0.05; n=6). To establish whether
      this effect was mediated at the high-affinity site we assessed the effects of
      elevated extracellular potassium on a biological model, neonatal mouse myocytes,
      that expressed solely the high-affinity binding sites. The K(d) values for
      binding to fetal mouse cardiac myocytes at an extracellular K+ of 5 mM and 20 mM
      were also significantly different, 29+/-10 and 230+/-46 nM, respectively. In
      conclusion, [3H]dofetilide binding to its high-affinity site is modulated by
      extracellular potassium.

PMID- 9040034
TI  - Reduction of I(Ca,L) and I(to1) density in hypertrophied right ventricular cells
      by simulated high altitude in adult rats.
AB  - The present paper describes the effect of a simulated hypobaric condition (at the
      altitude of 4500 m) on morphological characteristics and on some ionic currents
      in ventricular cells of adult rats. According to current data, chronic high
      altitude exposure led to mild right ventricular hypertrophy. Increase in right
      ventricular weight appeared to be due wholly or partly to an enlargement of
      myocytes. The whole-cell patch-clamp technique was used and this confirmed, by
      cell capacitance measurement, that chronic high-altitude exposure induced an
      increase in the size of the right ventricular cells. Hypertrophied cells showed
      prolongation of action potential (AP). Four ionic currents, playing a role along
      with many others in the precise balance of inward and outward currents that
      control the duration of cardiac AP, were investigated. We report a significant
      decrease in the transient outward (I(to1)) and in the L-type calcium current
      (I(Ca,L)) densities while there was no significant difference in the delayed
      rectifier current (I(K)) or in the inward rectifier current (I(K1)) densities in
      hypertrophied right ventricular cells compared to control cells. At a given
      potential the decrease in I(to 1) density was relatively more important than the
      decrease in I(Ca,L) density. In both cell types, all the currents displayed the
      same voltage dependence. The inactivation kinetics of I(to 1) and I(Ca,L) or the
      steady-state activation and inactivation relationships were not significantly
      modified by chronic high-altitude exposure. We conclude that chronic high
      altitude exposure induced true right ventricular myocyte hypertrophy and that the
      decrease in I(to 1) density might account for the lengthened action potential, or
      have a partial effect.

PMID- 9040035
TI  - Oxygen radicals released during ischemic preconditioning contribute to
      cardioprotection in the rabbit myocardium.
AB  - Previous studies have proposed that oxygen radicals may play a role in the
      triggering of ischemic preconditioning. However, studies evaluating the effects
      of radical scavengers have yielded conflicting results, possibly because of
      differences in the number of preconditioning episodes used. The present study
      tested whether N-2-mercaptopropionylglycine (MPG) could block protection of both
      single and multiple episodes of preconditioning in in situ and in vitro rabbit
      hearts. All hearts were subjected to 30 min of regional ischemia followed by
      reperfusion for 2 (in vitro) or 3 (in situ) h. Infarct size was measured by
      tetrazolium. Infarction in control in situ hearts was 37.5+/-3.5% of the risk
      zone. A single cycle of preconditioning (PC1), with 5 min ischemia/10 min
      reperfusion, reduced infarct size to 12.3+/-2.0% (P<0.05). Four cycles of
      preconditioning (PC4) were equally protective. MPG (1 mg/kg/min i.v.) alone had
      no effect on infarction but abolished protection afforded by PC1 (35.4+/-3.9%).
      However, MPG failed to block protection in the PC4 group. In isolated control
      hearts, infarct size was 31.1+/-1.8% and was reduced to 10.2+/-2.2% (P<0.05) by
      preconditioning. MPG (300 microM) aborted protection. Infusion of hypoxanthine or
      xanthine oxidase separately in lieu of preconditioning had no effect on infarct
      size, but induced protection when combined (14.1+/-2.2%; P<0.05). Polymyxin B, an
      inhibitor of protein kinase C (PKC), abolished this protection (53.1+/-4.1%). In
      conclusion, oxygen radicals contribute to ischemic preconditioning in the rabbit
      and appear to do so via activation of PKC. The fact that MPG could not block
      protection by PC4 suggests that oxygen radicals act in concert with other
      triggers of preconditioning such as adenosine and bradykinin.

PMID- 9040036
TI  - Coronary endothelial dysfunction precedes heart failure and reduction of coronary
      reserve in awake dogs.
AB  - Endothelial dysfunction in coronary circulation is well documented in heart
      failure (HF). However, whether this dysfunction is a consequence of heart failure
      or precedes the development of HF remains unknown. To determine endothelium
      dependent regulation in the remote coronary vasculature in a canine coronary
      microembolization-induced HF model, seven dogs were chronically instrumented for
      measurement of systemic hemodynamics, for selective coronary microembolization
      via an implanted coronary catheter and for measurement of coronary blood flow in
      the non-embolized coronary artery. Microembolizations were performed daily until
      hemodynamic and echocardiographic measurements showed HF. The responses of
      coronary blood flow to acetylcholine (0.25, 0.5, 5, 10 microg/kg), nitroglycerin
      (0.2, 0.8, 5, 25 microg/kg), adenosine (0.25, 0.5, 2, 5 micromol/kg) and brief
      coronary occlusions (5, 10, 15, 20, 30 s) were examined. Although no signs of HF
      developed and the responses of coronary blood flow to nitroglycerin, adenosine
      and occlusions were not altered, the response to acetylcholine was selectively
      reduced after 1 week of embolization (275,000+/-55,000 microspheres). Resting
      coronary flow increased from 21.3+/-1.4 ml/min in control state to 27.7+3.5
      ml/min (P<0.001). As HF developed, characterized by an elevated left ventricular
      end-diastolic pressure (6.4+/-1.6 v 16+/-1.6 mmHg, P<0.001), a decreased area
      ejection fraction (54+/-5 v 36+/-5%, P<0.05) and a reduced beta-adrenergic
      response to isoproterenol, the responses of coronary blood flow to acetylcholine,
      nitroglycerine, adenosine and occlusions were consistently depressed. Resting
      coronary blood flow was decreased to 15.4+/-2.7 ml/min (P<0.01). Our results
      indicate, that there is a selectively impaired endothelium-mediated dilator
      capacity of the resistance coronary vasculature before the development of HF and
      a reduction of the coronary flow reserve.

PMID- 9040037
TI  - Protective effect of dextran sulfate and heparin on adult rat cardiomyocytes
      damaged by free radicals.
AB  - Studies in our laboratory have demonstrated that addition of polyanions, heparin
      or dextran sulfate, to endothelial cell cultures decrease free radical injury. To
      determine if these polyanions had a similar effect on cardiomyocytes, models of
      free radical injury were produced in adult rat cardiomyocyte cultures by: (1)
      addition of hydrogen peroxide; (2) exposure to hypoxia followed by reoxygenation;
      or (3) exposure to medium conditioned by endothelial cells that were damaged by
      hypoxia-reoxygenation. All three procedures significantly decreased cell
      viability as measured by trypan blue exclusion and increased release of enzymes,
      lactate dehydrogenase and creatine kinase, into cell medium when compared to
      control cultures. Addition of dextran sulfate or heparin to medium (5 microg/ml)
      prior to cell injury significantly increased cell viability and decreased release
      of enzymes when cells were damaged by the above protocols. Heparin was
      significantly less protective than dextran sulfate when cells were injured by
      hydrogen peroxide or hypoxia-reoxygenation but not when conditioned medium from
      damaged endothelial cells was added to cardiomyocytes. These results indicate
      that polyanions are protective of cardiomyocytes as well as endothelium. This
      protective effect may contribute to the beneficial effects of heparin on the
      cardiovascular system.

PMID- 9040038
TI  - Identification of changes in cardiac phospholipase C activity in congestive heart
      failure.
AB  - Although phosphoinositide-specific phospholipase C (PLC) is involved in signal
      transduction mechanisms of the myocardial cell. very little is known about its
      status in congestive heart failure (CHF). We have examined the PLC activity in
      sarcolemmal and cytosolic fractions isolated from the viable left ventricle of
      rats at 8 weeks (moderate stage of CHF) and 16 weeks (severe stage of CHF) after
      occlusion of the left anterior descending coronary artery; the hypertrophied
      right ventricle was used for comparison. At 8 weeks, the hydrolysis of
      phosphatidylinositol 4,5-bisphosphate by sarcolemmal PLC was reduced by 37% of
      sham control values only in the left ventricle, whereas at 16 weeks, PLC-mediated
      hydrolysis was depressed in both left and right ventricles by 25% and 30%,
      respectively. The hydrolysis of phosphatidylinositol 4-monophosphate (PIP) was
      reduced by 25% of control value only in the severely failing left ventricle,
      while the phosphatidylinositol (PI) hydrolysis remained unaltered. Kinetic
      studies of PLC activity in the left ventricle showed a depression of V(max) at
      moderate and severe failure stages, whereas the affinity for the substrate was
      increased in the left ventricle at 8 weeks and decreased in the right ventricle
      at 16 weeks. The only difference observed between experimental and control groups
      at the cytosolic level, was a significant enhancement of PLC activity in the
      severely failing left ventricle when PIP was given as a substrate, and in the
      corresponding right ventricle when PI was the substrate. The results of this
      study identify time-related defects in sarcolemmal PLC in right and left
      ventricles during the development of CHF due to myocardial infarction.

PMID- 9040039
TI  - Mechanism of cardiac involvement in the WBN/Kob rat.
AB  - The cardiac characteristics of the WBN/Kob rat resemble those of rats with
      catecholamine-induced myocarditis. To determine the etiology of these WBN cardiac
      characteristics, we assessed the number and affinity of beta-adrenergic
      receptors, and investigated adenylate cyclase activity, the cardiac myocyte
      cyclic adenosine monophosphate (cAMP) concentration and the activity of guanosine
      triphosphate (GTP)-binding protein in 3-month-old WBN/Kob rats. Age-matched
      Wistar rats served as controls. The mean number of beta-adrenergic receptors was
      similar in WBN/Kob and Wistar rats (28.0+/-9.1 v 28.3+/-8.9 fmol/mg protein), and
      there was no significant difference in beta-adrenergic receptor affinity between
      groups (1.09+/-0.54 v 1.26+/-0.60 nM). The mean cAMP concentration in cardiac
      myocytes was significantly higher in WBN/Kob rats than in Wistar rats 1975.6+/
      247.8 v 344.9+/-83.6 pmol/g wet tissue), (P=0.0112) as was adenylate cyclase
      activity (33.61+/-8.32 v 24.3+/-12.78 pmol/mg/min), (P=0.0174). The activity of
      GTP-binding protein was significantly higher in WBN/Kob rats than in Wistar rats.
      After a beta-agonist binds to a beta-adrenergic receptor, activated adenylate
      cyclase produces cAMP in myocytes, which in turn opens the Ca2+ channel, leading
      to an influx of Ca2+ into myocytes. Our results suggest that the increase in
      adenylate cyclase activity in WBN/Kob rats have led to an increase in the cAMP
      concentration in myocytes. This process may have resulted in excessive beta
      adrenergic activity due to high activity of GTP binding protein in WBN/Kob rats,
      which may explain the hypersensitivity of WBN/Kob rats to isoproterenol and the
      development of catecholamine-induced myocarditis.

PMID- 9040040
TI  - Differences in expression of sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+
      exchanger genes between adjacent and remote noninfarcted myocardium after
      myocardial infarction.
AB  - Although cardiac failure can develop over time after myocardial infarction, the
      mechanism responsible for this is still unknown. The change of intracellular Ca2+
      transport protein, such as sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+
      Ca2+ exchanger (Na+-Ca2+), or cardiac phenotypic modulation of contractile
      protein in noninfarcted myocardium may have a important role. However, the time
      course in gene expression of sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+),
      Na+-Ca2+ exchanger (Na+-Ca2+), and contractile protein in the adjacent and remote
      noninfarcted myocardium after myocardial infarction has not been examined. At 1,
      3 weeks and 3 months after myocardial infarction, hemodynamics were measured and
      mRNA of the left ventricle was analyzed. Left ventricular end-diastolic volume
      and weight increased both with time. Ascites became apparent at 3 months after
      infarction. SR-Ca2+ mRNA levels in the adjacent noninfarcted myocardium were 0.7-
      (P<0.01), 0.9- (N.S.), and 0.7-fold (P<0.01) of control, and Na+-Ca2+ mRNA levels
      were 2.1- (P<0.01), 1.4- (P<0.01), and 0.8-fold (P<0.01) of control, at 1, 3
      weeks and 3 months after infarction, respectively. beta-Myosin heavy chain (MHC)
      mRNA was increased to 2.1- (P<0.01), 1.5- (P<0.01), and 1.4-fold (P<0.01), and
      alpha-skeletal actin was increased to 2.4- (P<0.01), 3.8- (P<0.01), and 1.6-fold
      (P<0.01) control levels, at 1 week, 3 weeks and 3 months, respectively. In
      contrast, alpha-MHC mRNA level was decreased at 1 week and 3 months after
      infarction. alpha-cardiac actin mRNA level did not change over time after
      infarction. In the remote non-infarcted myocardium, beta-MHC, alpha-skeletal
      actin, and Na+-Ca2+ mRNA levels were increased, but SR-Ca2+, alpha-MHC, and alpha
      cardiac actin mRNA did not change after infarction. These findings suggest that:
      (1) intracellular Ca2+ handling system after myocardial infarction may be
      different between adjacent and remote non-infarcted myocardium: and that (2) both
      decreased gene expression of SR Ca2+-ATPase and Na+-Ca2+ exchanger in the
      adjacent non-infarcted myocardium may progress cardiac dysfunction.

PMID- 9040041
TI  - Increased expression of cardiac phosphatases in patients with end-stage heart
      failure.
AB  - Type 1 phosphatase activity was increased in membrane vesicles from failing human
      ventricles compared with non-failing controls. Likewise, expression of the mRNA
      encoding for type 1 phosphatase was enhanced by 37%. The present study provides
      evidence that alterations of phosphatase activity coincide with end-stage heart
      failure. Thus, enhanced activity of phosphatases may be causally related to heart
      failure and/or may aggravate the well known decreased cardiac responsiveness to
      positive inotropic agents in end-stage heart failure.

PMID- 9040042
TI  - Transforming growth factor-betas block cytokine induction of catalase and
      xanthine oxidase mRNA levels in cultured rat cardiac cells.
AB  - We examined the effects of transforming growth factor-beta (TGF-beta) on the mRNA
      expression of the antioxidative enzymes, catalase, manganese superoxide dismutase
      (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD), as well as the oxidative
      enzyme, xanthine oxidase (XO), in cultures of cardiomyocytes, cardiac non
      myocytes, and fetal bovine heart endothelial cells. TGF-betas alone had little
      effect on expression of these enzymes, but treatment with a combination of
      interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha increased
      expression of MnSOD, catalase, and XO in some cell types with little effect on
      CuZnSOD expression. When TGF-betas were added along with these inflammatory
      cytokines there was a return to control levels of catalase expression, as well as
      a dramatic reduction in XO expression. In fetal bovine heart endothelial cells,
      treatment with inflammatory cytokines increased XO mRNA expression 11.5-fold and
      inclusion of TGF-betas reduced this 4-5-fold: effects on XO enzyme activity
      paralleled those seen on mRNA expression. Similar changes in XO expression were
      seen in cardiomyocytes. In contrast, TGF-betas did not change cytokine-induced
      MnSOD expression. All three mammalian isoforms of TGF-beta showed similar
      effects. In summary, TGF-betas may be able to decrease superoxide anion
      production and subsequent tissue damage by decreasing levels of XO.

PMID- 9040043
TI  - Identification of genes encoding zinc finger motifs in the cardiovascular system.
AB  - The Zn2+-finger DNA-binding domain has been identified in several developmental
      control proteins, transcription factors and gene products associated with
      diseases, as well as in several RNA-binding proteins. We applied library
      screening, expressed sequence tagging (EST sequencing), Zn2+-binding assays and
      Northern blot hybridization, in order to characterize novel cDNA clones of the
      human cardiovascular system which contain Zn2+-finger motifs. An embryonic (8-10
      weeks gestation) heart lambda ZAP Express cDNA library was screened with an
      oligonucleotide probe deduced from a consensus amino acid sequence which is
      highly conserved for Zn2+-finger proteins, and approximately 350 positive clones
      were isolated from 1 x 10(4) plaque-forming units (pfu) initially plated. The
      isolated clones were classified as known and novel following single pass
      automated DNA sequencing. Analysis of Northern blot hybridization delineated the
      tissue specificity of these clones, as well as their association with cardiac
      growth and development. Existence of Zn2+-finger motifs in the novel clones was
      confirmed by Zn2+-binding assay. In this report, we present the characterization
      of eight novel clones, including the complete cDNA sequences of one of these
      clones (HHZ-123).

PMID- 9040044
TI  - Ischemia and reperfusion of the porcine myocardium: effect on collagen.
AB  - We studied the effect of acute myocardial infarction and late reperfusion on
      myocardial collagen in a closed chest porcine model, to investigate if any
      collagen degradation could be detected in blood samples and myocardium. Sixteen
      60-80 kg pigs were used with six animals serving as controls and 10 submitted to
      ischemia-reperfusion. In the ischemia-reperfusion group the left anterior
      descending coronary artery was occluded for 6 h by inflation of a percutaneous
      transluminal coronary angioplasty balloon followed by reperfusion for 3 h. Blood
      samples were taken from the aorta and the coronary sinus and analyzed for
      creatine kinase and collagen degradation products, i.e. the N-terminal propeptide
      of procollagen type III (PIIINP) and C-terminal pyridinoline cross-linked
      telopeptide of collagen type I (ICTP). Myocardial tissue samples were analyzed
      for content of hydroxyproline, collagen volume fraction and amount of extractable
      PIIINP/dry weight. Transmission electron microscopy of biopsies was performed to
      evaluate myocytes and collagen structure outside and within the infarct zone.
      Creatine kinase showed a statistically significant increase during ischemia and
      reperfusion but we found no evidence of release of collagen degradation products
      either during ischemia or reperfusion compared with control. Myocardial content
      of hydroxyproline, collagen volume fraction and extractable PIIINP/dry weight did
      not differ between groups. Transmission electron microscopy of biopsies from the
      infarct zone showed myocyte damage but no visible evidence of collagen
      degradation when photos were evaluated blindly. In this porcine model of acute
      myocardial infarction and late reperfusion no release of collagen degradation
      products from the myocardium or any decrease in or damage to myocardial collagen
      was detected.

PMID- 9040045
TI  - Clofilium-induced block of delayed rectifier type K+ current in atrial tumor
      cells (AT-1 cells).
AB  - Atrial tumor myocytes derived from transgenic mice (AT-1 cells) have been shown
      to express mRNAs encoding cardiac K+ channels and display a cardiac
      electrophysiological phenotype. The major K+ current is the rapid component of
      the delayed rectifier (I(kr)). The purpose of the study was to characterize the
      mode of action of a class III anti-arrhythmic agent (C3A), clofilium, in these
      cells to elucidate further the mechanism and functional consequence of block. We
      show that clofilium blocks this I(kr) in a dose-dependent manner with IC50 of
      1.25 microM. Clofilium induced block was irreversible for higher concentrations
      (> or = 50 microM) and partially reversible for lower doses. The reversal
      potential for this current was -77.5+/-1.5 mV. The block is voltage dependent and
      the drug probably binds the channel in the open state.

PMID- 9040046
TI  - beta-Adrenergic and muscarinic receptor expression are regulated in opposite ways
      during senescence in rat left ventricle.
AB  - The well-known attenuated sensitivity of senescent heart to isoproterenol is
      accompanied by a decreased beta1-adrenergic receptors (beta1-AR) density, a down
      regulation process which may involve several molecular modifications and whose
      understanding is incomplete. Data concerning the M2-R muscarinic receptors (M2-R)
      are more contradictory. Both the absolute and relative concentrations of beta1-AR
      and M2-R as well as the coupling protein G alpha s and G alpha(i2) mRNAs were
      determined by slot-blot analysis in the left ventricles (LVs) of 6-7 week and 22
      month-old male Wistar rats. In addition, the beta-AR and M2-R densities were
      quantitated by radioactive ligand binding. (1) The M2-R mRNA concentration
      increases by 92+/-32% in senescent as compared to adult animals; by contrast, the
      density in M2-R remains unchanged, suggesting that the M2-R expression was not
      exclusively regulated at a pre-translational level. (2) The beta1-AR mRNA
      concentration was nearly halved (reduced by 46+/-9.5%) and paralleled the 51+/
      5.6% diminution of the beta-AR density which resulted exclusively from the
      decrease of beta1-AR density without change in the beta2-AR concentration,
      suggesting a pre-translational regulation of the beta1-AR expression. (3) G
      alpha(i2) mRNA concentration was unchanged, while G alpha s mRNA concentration
      was reduced by 26+/-4.6% in senescent compared with adult LVs. To conclude, the
      different components of the adrenergic and muscarinic systems are differentially
      regulated during aging.

PMID- 9040047
TI  - Cardiac Na+-H+ exchanger during postnatal development in the rat: changes in mRNA
      expression and sarcolemmal activity.
AB  - We examined Na+-H+ exchanger isoform 1 (NHE-1) mRNA expression in ventricular
      myocardium and its correlation with sarcolemmal NHE activity in isolated
      ventricular myocytes, during postnatal development in the rat. The expression of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA did not change in
      ventricular myocardium between 2 and 42 days after birth. Therefore, at seven
      time points within that age range. GAPDH expression was used to normalize NHE-1
      mRNA levels, as determined by reverse transcription polymerase chain reaction
      analysis. There was a progressive five-fold reduction in NHE-1 mRNA expression in
      ventricular myocardium from 2 days to 42 days of age. As an index of NHE
      activity, acid efflux rates (J(H)) were determined in single neonatal (2-4-day
      old) and adult (42-day-old) ventricular myocytes (n=16/group) loaded with the pH
      fluoroprobe carboxy-seminaphthorhodafluor-1. In HEPES-buffered medium, basal
      intracellular pH (pH(i)) was similar at 7.28+/-0.02 in neonatal and 7.31+/-0.02
      in adult myocytes, but intrinsic buffering power was lower in the former age
      group. The rate at which pH(i) recovered from a similar acid load was
      significantly greater in neonatal than in adult myocytes (0.36+/-0.07 v 0.16+/
      0.02 pH units/min at pH(i)=6.8). This was reflected by a significantly greater
      J(H) (22+/-4 v 9+/-1 pmol/cm2/s at pH(i)=6.8), indicating greater sarcolemmal NHE
      activity in neonatal myocytes. The concomitant reductions in tissue NHE-1 mRNA
      expression and sarcolemmal NHE activity suggest that myocardial NHE-1 is subject
      to regulation at the mRNA level during postnatal development.

PMID- 9040048
TI  - Exogenous adenosine, supplied transiently during reperfusion, ameliorates
      depressed endogenous adenosine production in the post-ischemic rat heart.
AB  - Adenosine (ADO) is an important endogenous protective metabolite of the heart
      which also exerts beneficial effects when exogenously supplied before or after
      ischemia. Previous studies established that after initial massive release of ADO,
      its endogenous production could be significantly reduced following myocardial
      ischemia. However, the mechanism and consequences of this phenomenon are not
      clear. We investigated whether this suppressed endogenous ADO production could be
      reversed by a transient supply of exogenous ADO during reperfusion. Furthermore,
      we studied the recovery of mechanical function, coronary flow and myocardial
      nucleotide levels after this intervention. Three concentrations of ADO were
      applied: 1 microM, which exerts maximal vasodilatation: 30 microM, optimal for
      adenylate resynthesis: and 1 mM which exerts a cardioplegic effect. Rat hearts
      perfused in the Langendorff mode were divided into five groups (n = 6-9 per
      group): all hearts had transient (30-s) ischemia at 20 min (TI-1) and 70 min (TI
      3) of perfusion. Group 1 (control) had an additional transient (30-s) ischemia at
      45 min (TI-2). Group 2 (ischemic control) had 10-min ischemia at 30 min: groups
      3, 4 and 5 also had 10-min ischemia at 30 min but were reperfused for the initial
      15 min with 1 microM, 30 microM or 1 mM ADO. Developed tension, coronary flow and
      coronary effluent purines and pyrimidines were measured throughout the 75-min
      experimental period. Nucleotide content was evaluated in freeze-clamped hearts at
      the end of the experiment. Endogenous ADO release to the coronary effluent
      increased immediately after TI-1 in all groups. This increase was similar after
      TI-1 and after TI-3 in control, while it was reduced to 30% in ischemic control
      group. In the 30 microM ADO group the increase in endogenous ADO release after TI
      3 was restored and was similar to that after TI-1. A similar trend was observed
      with 1 mM ADO, while in 1 microM group recovery of endogenous ADO release after
      TI-3 was not observed. The highest recovery of developed tension (+ S.E.)
      occurred with 1 microM and 30 microM ADO (72 +/- 3% and 72 +/- 5% of pre-ischemic
      value, respectively) compared to 53 +/- 5% and 63 +/- 5% in ischemic control and
      1 mM ADO groups, respectively (P <0.05). Coronary flow was restored 30 s after 10
      min ischemia in hearts treated with 1 microM and 30 microM ADO, whereas more than
      2 min were necessary in ischemic control or 1 mM ADO groups. Furthermore,
      hyperemic response after TI-3 was significantly enhanced in the 1 microM or 30
      microM ADO groups. ATP content at the end of reperfusion was highest in the 30
      microM ADO group (18.9 +/- 0.5 micromol/g dry wt.) as compared to ischemic
      control. 1 microM or 1 mM ADO groups (15.2 +/- O.6, 16.4 +/- 0.4, and 17.2 +/-
      0.4 micromol/g dry wt. respectively). Concentrations of other nucleotide
      triphosphates (GTP, UTP and CTP) were similar in all hearts subjected to 10-min
      ischemia. In summary, depressed endogenous ADO production in the post-ischemic
      heart could be ameliorated by transient supply of exogenous ADO during
      reperfusion at 30 microM concentration. This effect was found to be related to
      the elevation of the adenine nucleotide pool. However, restoration of endogenous
      ADO production was not necessary for improvement in the recovery of mechanical
      function by exogenous ADO.

PMID- 9040049
TI  - Mitochondrial function is not decreased in stunned papillary muscle at 20 degrees
      C.
AB  - It is unclear to what extent mitochondrial function in vivo is changed after
      brief anoxia. Heat measurements allow evaluation of mitochondrial function within
      intact cardiac muscle. Heat production was determined using fast metal-film
      thermopiles, during contraction and post-contractile recovery in control and
      stunned superfused rabbit papillary muscles at 20 degrees C. Heat rate was
      measured for a train of ten twitches (0.2 Hz) before anoxia and after 40 min
      anoxia followed by 2 h of normoxic recovery. During anoxia muscles were
      stimulated at 0.2 Hz (group A) or at 1.0 Hz (group B). A normoxic control group C
      was stimulated at 0.2 Hz. After 2 h recovery, tension was 77 +/- 5% (S.E.M.), 72
      +/- 7% and 94 +/- 3% of initial values, for group A, B and C respectively,
      indicating stunning by anoxia. The economy of contraction or the ratio of
      recovery heat to initial heat did not change significantly in groups A and B when
      compared with control, indicating that stunning with this protocol is not
      associated with mitochondrial uncoupling. Post-contractile recovery heat
      initially decayed exponentially with time constant 24.9 +/- 2.2 s for all groups
      and with 22.7 +/- 1.1, 22.0 +/- 0.8 and 41.7 +/- 4.4 s at the end for group A, B
      and C respectively. The cause of the remarkable slowing of the recovery rate over
      time in controls is unknown, but is mimicked by blocking fatty acid utilization.
      No slowing of metabolic recovery is observed in the stunned papillary muscles. We
      conclude that stunning is not associated with a decrease in mitochondrial
      function or oxidative capacity in cardiac muscle.

PMID- 9040050
TI  - PDGF-AA, a potent mitogen for cardiac fibroblasts from adult rats.
AB  - The heart responds to increased haemodynamic load with growth of the ventricles.
      The rise in ventricle mass is due to increasing mass of the myocytes and
      proliferation of fibroblasts and smooth muscle cells. The accompanying adaptation
      and remodelling of the interstitium, e.g. production and composition of the
      extracellular matrix proteins, determine a physiological or pathophysiological
      hypertrophy. Fibroblasts play a critical role in this process as the producers of
      extracellular matrix proteins. So far the growth factors involved are not well
      defined, and therefore we investigated the effect of platelet-derived growth
      factor (PDGF) isoforms on cellular proliferation of fibroblasts from adult rat
      hearts. Unlike other cell types of the cardiovascular system (e.g. smooth muscle
      cells), PDGF-AA has an extraordinarily high stimulatory effect on cell growth of
      these fibroblasts. It induces cell division to nearly the same extent and with
      the same kinetics as PDGF-BB as shown by cell number and flow cytometry. Cardiac
      fibroblasts do not express an unusually high number of PDGF alpha-receptors,
      (15300 PDGF alpha-receptors. 24800 PDGF beta-receptors per cell) which could
      explain this effect. The alpha-receptors display a lower and shorter
      autophosphorylation after stimulation with PDGF in comparison to the beta
      receptors. The activation of the MAP kinase pathway is not different after
      stimulation with both PDGF isoforms. Interestingly, quiescent cardiac fibroblasts
      contain a preactivated p70S6-kinase. The specific drug rapamycin not only
      inhibits the p70S6-kinase activation but also PDGF induced cell proliferation for
      more than 50%. Because the p70S6-kinase activation is implicated in growth
      regulation in this cell system, the preactivation of this kinase is discussed to
      be a possible explanation for the enhanced growth effect of PDGF-AA.

PMID- 9040051
TI  - Analysis of heart development in cultured rat embryos.
AB  - The long-range goal of this research is to establish an in vitro system that will
      permit pertubation of mammalian heart development and in situ examination of the
      cellular and molecular events underlying cardiac morphogenesis. Rat embryos at
      9.5-11.5 days of gestation were placed in culture bottles containing rat serum
      and Tyrode's solution. Embryos cultured for 24 and 48 h were compared to age
      matched in vivo controls for morphological score, morphometric analysis of heart
      development, and confocal and electron microscopic analysis of myofiber pattern
      formation. Morphological scores indicated that embryos cultured for 24 h from day
      9.5 to 10.5 had essentially normal development when compared to age-matched
      embryos allowed to develop in vivo. Development of embryos maintained for 48 h in
      culture was slightly delayed at 66-68% of age matched in vivo embryos. Analysis
      of hearts from embryos allowed to develop 9.5-11.5 days in vivo plus 24 and 48 h
      in culture showed that the ventricular thickness and height, as well as the
      truncal, atrial and ventricular diameters were equivalent to those of hearts from
      age-matched in vivo controls. Hearts from embryos allowed to develop from 11.5
      12.5 days in vitro and cultured for 24 and 48 h had smaller left ventricular and
      atrial dimensions than controls. Cardiac myofibrillogenesis and myofibrillar
      pattern formation in embryos cultured from 9.5 days of in vivo development for 48
      h were also normal. These studies indicate that the rat whole embryo culture
      system is a useful model to study several critical periods in mammalian heart
      development.

PMID- 9040052
TI  - The cardiac troponin C isoform and the length dependence of Ca2+ sensitivity of
      tension in myocardium.
AB  - The Ca2+ sensitivity of tension in cardiac muscle is length dependent, such that
      the sensitivity is diminished with decreasing sarcomere length below 2.4 microm.
      This length dependence of Ca2+ sensitivity of tension also forms the basis for
      the Frank-Starling mechanism in the heart. The fast-twitch skeletal muscle has a
      much lower length dependence of Ca2+ sensitivity. In a recent study of skinned
      cardiotrabeculae, we indicated that the exchange of endogenous cardiac troponin C
      (TnC) for skeletal troponin C also resulted in a major reduction in the length
      dependence to the level of skeletal muscle. These findings suggested that cardiac
      troponin C has a key role in the length-sensing mechanism. The present
      investigation supports this conclusion and delineates the specific domain in
      cardiac TnC responsible for the length effect. Chimeras splicing either 41, 61,
      or 96 N-terminal cardiac amino acids with the remaining skeletal residues have
      indicated that while Ca2+ binding in all three constructs is similar to that in
      wild type cardiac TnC, the functional responsiveness of the 96-cardiac residue
      construct is improved over the other two. This 96-cardiac residue construct
      yielded a tension response indistinguishable from that of wild-type cardiac TnC.
      A tryptophan variant of the chimera indicated fluorescence characteristics
      indistinguishable from cardiac troponin C. The findings provide further support
      for the idea that cardiac troponin C in situ is modified in response to sarcomere
      length change and thereby participates in the Frank-Starling mechanism. Moreover,
      the study indicates that the tropinin C length-sensing attribute originates
      within the N-terminal domain constituted by these 96 residues.

PMID- 9040053
TI  - Differential regulation of extracellular matrix metalloproteinase and tissue
      inhibitor by heparin and cholesterol in fibroblast cells.
AB  - Heparin has been shown to stimulate angiogenesis in the border zones surrounding
      infarcted myocardium. Matrix metalloproteinases (MMP), which are involved in
      extracellular matrix (ECM) organization, have also been shown to be activated.
      Cholesterol is required for receptor signaling in the plasma membrane, but a role
      of MMPs for cholesterol in ECM remodeling has not yet been shown. To examine
      whether heparin and cholesterol induce MMP and tissue inhibitor of
      metalloproteinase (TIMP) in human heart fibroblast (HHF) cells, confluent HHF
      cells were treated with cholesterol (100 microM) or heparin (20 microM). MMP
      activity was measured using zymography and TIMP was measured by Western blot
      analysis. The number of HHF cells, measured by a hemocytometer, increased after
      heparin or cholesterol treatment. Gelatinase A (MMP-2) activity increased in
      heparin treated cells, and the TIMP-1 level increased in cholesterol-treated
      cells. Based on Northern blot analysis, we observed that both MMP-1 and MMP-2
      were induced at the gene transcription level by heparin and that TIMP-1 was
      induced by cholesterol. To examine whether the effects of heparin and cholesterol
      were due to Ca2+ mobilization, we carried out Ca2+ transient assays using FURA
      2/AM as a fluorescence probe in HHF cells. Heparin induced a slow rise in the
      Ca2+ transient with a slow decay, and cholesterol induced a rapid rise with a
      slow reversal to the baseline calcium level. This suggested that the effect of
      heparin on Ca2+ release from HHF may be secondary to the receptor binding on the
      cell membrane but that cholesterol may have a direct effect. Protein kinase
      inhibitor and Ca2+-channel blocker have been shown to inhibit MMP expression. To
      examine whether the effect of heparin on MMP expression is mediated through the
      collagenase promoter activity, we carried out gel-shift assays using a 21
      oligonucleotide analogue to the MMP-1 promoter sequence. Results suggested that
      the increase in MMP promoter activity by heparin is due to a specific
      transcription factor binding to MMP-1 promoter sequence. The effect of
      cholesterol on fibroblast cell proliferation is due in part to the tissue
      inhibitor. This study demonstrated the role of heparin and cholesterol in ECM
      remodeling and has implications for angiogenesis and athersclerosis,
      respectively.

PMID- 9040054
TI  - Ontogeny of sarcoplasmic reticulum protein phosphorylation by Ca2+--calmodulin
      dependent protein kinase.
AB  - In the adult myocardium the Ca2+ uptake and release functions of the sarcoplasmic
      reticulum (SR) are known to be regulated by a membrane-associated Ca2+-calmodulin
      dependent protein kinase (CaM kinase) which phosphorylates the Ca2+-pumping
      ATPase (Ca2+ pump), Ca2+ release channel (ryanodine receptor) and the Ca2+ pump
      regulatory protein, phospholamban. The role of CaM kinase during development,
      however, has not been examined previously. The present study investigated the
      ontogenetic expression of SR-associated CaM kinase in the rabbit myocardium as
      well as development-related changes in CaM kinase-mediated phosphorylation of the
      SR proteins (Ca2+ pump, Ca2+ release channel and phospholamban) involved in
      transmembrane Ca2+ cycling. For these experiments, cardiac muscle homogenate and
      SR-enriched membrane fraction derived from fetal (21- and 28-days gestation),
      newborn (2 days postnatal) and adult New Zealand White rabbits were used. Western
      immunoblotting analysis detected the presence of phospholamban, Ca2+ pump and
      Ca2+ release channel in homogenate and SR at all ages tested. The amount of these
      proteins in the SR increased substantially during fetal and postnatal
      development. Phosphorylation studies revealed the presence of CaM kinase
      dependent phosphorylation of the Ca2+ pump, Ca2+ release channel and
      phospholamban as early as 21-days gestation. This phosphorylation could be
      elicited with the addition of only Ca2+ and calmodulin indicating the presence of
      a SR-associated CaM kinase as early as 21-days gestation. This was confirmed
      using a delta-CaM kinase II-specific antibody. Phosphorylation per unit amount of
      each substrate was greater in the fetus and newborn compared to adult.
      Phosphorylation of phospholamban could be elicited by exogenous cAMP-dependent
      protein kinase (PKA) at all developmental stages studied. Activation of SR CaM
      kinase with Ca2+ and calmodulin, or induction of phospholamban phosphorylation by
      exogenous PKA, resulted in stimulation of the Ca2+ uptake activity of SR in
      fetal, newborn and adult heart. These results demonstrate early ontogenetic
      expression of the Ca2+ cycling proteins and CaM kinase in the SR and the
      concurrent development of phosphorylation-dependent regulation of SR Ca2+
      cycling.

PMID- 9040056
TI  - Purification and characterization of human heart fatty acid ethyl ester
      synthase/carboxylesterase.

PMID- 9040055
TI  - Plasma levels of the monocyte chemotactic and activating factor/monocyte
      chemoattractant protein-1 are elevated in patients with acute myocardial
      infarction.
AB  - Cardiac inflammatory responses appear to play a pivotal role in scar formation
      after acute myocardial infarction. Monocyte chemotactic and activating factor
      (MCAF) monocyte chemoattractant protein-1 (MCP-1) is a cytokine with chemotactic
      activity for mononuclear phagocytes, but also for NK cells, T cells, mast cells,
      and basophils. To investigate the possible involvement of MCAF/MCP-1 in the
      pathogenesis, its course was studied in patients with acute myocardial
      infarction. Twenty-three consecutive patients with acute myocardial infarction
      and 18 patients with angina pectoris were studied. Cytokines were measured by
      enzyme-linked immunosorbent assay. Plasma levels of interleukin IL-1alpha, IL
      1beta, and IL-2 were below the detection limit of our method. IL-6 and interferon
      gamma were detected in 17.4%, and tumor necrosis factor-alpha in 13.0% of
      patients with acute myocardial infarction, but the frequency was not
      statistically significantly different from that in angina pectoris. The plasma
      level of MCAF/MCP-1 in myocardial infarction tended to increase at 3 h after the
      onset of chest pain (133 +/- 19 pg/ml, P= 0.06) and was significantly elevated at
      9 h (143 +/- 20 pg/ml) when compared with that in angina pectoris (87 +/- 6
      pg/ml, P<0.05). The MCAF/MCP-1 level remained increased during the 24-hours
      observation period (P<0.01), and maximum level (168 +/- 13 pg/ml) was seen at 24
      hour. The level of MCAF/ MCP-1 correlated significantly with the plasma level of
      another chemokine, IL-8, at 12 h after the onset of chest pain (r=0.51, P<0.05),
      suggesting that common stimuli mediate the release of both cytokines in
      myocardial infarction. The identification of MCAF/MCP-1 as an inflammatory
      mediator in acute myocardial infarction suggests that mononuclear phagocytes may
      play an important role in the early stage of the disease.

PMID- 9040057
TI  - Characterization of a human cardiac gene which encodes for a LIM domain protein
      and is developmentally expressed in myocardial development.

PMID- 9040058
TI  - Identification of coherent structures in turbulent shear flows with a fuzzy
      artmap neural network.
AB  - An implementation of a Fuzzy Artmap neural network is used to detect and to
      identify (recognise) structures (patterns) embedded in the velocity field of a
      turbulent wake behind a circular cylinder. The net is trained to recognise both
      clockwise and anticlockwise eddies present in the u and v velocity fields at 420
      diameters downstream of the cylinder that generates the wake, using a pre
      processed part of the recorded velocity data. The phase relationship that exists
      between the angles of the velocity vectors of an eddy pattern is used to reduce
      the number of classes contained in the data, before the start of the training
      procedure. The net was made stricter by increasing the vigilance parameter within
      the interval [0.90, 0.95] and a set of net-weights were obtained for each value.
      Full data files were scanned with the net classifying patterns according to their
      phase characteristics. The net classifies about 27% of the recorded signals as
      eddy motions, with the strictest vigilance parameter and without the need to
      impose external initial templates. Spanwise distances (homogeneous direction of
      the flow) within the centres of the eddies identified suggest that they form
      pairs of counter-rotating vortices (double rollers). The number of patterns
      selected with Fuzzy Artmap is lower than that reported for template matching
      because the net classifies eddies according to the recirculating pattern present
      at the core or central region, while template matching extends the region over
      which correlation between data and template is performed. In both cases, the
      topology of educed patterns is in agreement.

PMID- 9040059
TI  - A fuzzy adaptive learning control network with on-line structure and parameter
      learning.
AB  - This paper addresses a general connectionist model, called Fuzzy Adaptive
      Learning Control Network (FALCON), for the realization of a fuzzy logic control
      system. An on-line supervised structure/parameter learning algorithm is proposed
      for constructing the FALCON dynamically. It combines the backpropagation learning
      scheme for parameter learning and the fuzzy ART algorithm for structure learning.
      The supervised learning algorithm has some important features. First of all, it
      partitions the input state space and output control space using irregular fuzzy
      hyperboxes according to the distribution of training data. In many existing fuzzy
      or neural fuzzy control systems, the input and output spaces are always
      partitioned into "grids". As the number of input/output variables increase, the
      number of partitioned grids will grow combinatorially. To avoid the problem of
      combinatorial growing of partitioned grids in some complex systems, the proposed
      learning algorithm partitions the input/output spaces in a flexible way based on
      the distribution of training data. Second, the proposed learning algorithm can
      create and train the FALCON in a highly autonomous way. In its initial form,
      there is no membership function, fuzzy partition, and fuzzy logic rule. They are
      created and begin to grow as the first training pattern arrives. The users thus
      need not give it any a priori knowledge or even any initial information on these.
      In some real-time applications, exact training data may be expensive or even
      impossible to obtain. To solve this problem, a Reinforcement Fuzzy Adaptive
      Learning Control Network (RFALCON) is further proposed. The proposed RFALCON is
      constructed by integrating two FALCONs, one FALCON as a critic network, and the
      other as an action network. By combining temporal difference techniques,
      stochastic exploration, and a proposed on-line supervised structure/parameter
      learning algorithm, a reinforcement structure/parameter learning algorithm is
      proposed, which can construct a RFALCON dynamically through a reward/penalty
      signal. The ball and beam balancing system is presented to illustrate the
      performance and applicability of the proposed models and learning algorithms.

PMID- 9040060
TI  - Frequency-spatial transformation: a proposal for parsimonious intra-cortical
      communication.
AB  - This work examines a neural network model of a cortical module, where neurons are
      organized on a 2-dimensional sheet and are connected with higher probability to
      their spatial neighbors. Motivated by recent findings that cortical neurons have
      a resonant peak in their impedance magnitude function, we present a frequency
      spatial transformation scheme that is schematically described as follows: An
      external input signal, applied to a small input subset of the neurons, spreads
      along the network. Due to a stochastic component in the dynamics of the neurons,
      the frequency of the spreading signal decreases as it propagates through the
      network. Depending on the input signal frequency, different neural assemblies
      will hence fire at their specific resonance frequency. We show analytically that
      the resulting frequency-spatial transformation is well-formed; an injective,
      fixed, mapping is obtained. Extensive numerical simulations demonstrate that a
      homogeneous, well-formed transformation may also be obtained in neural networks
      with cortical-like "Mexican-hat" connectivity. We hypothesize that a frequency
      spatial transformation may serve as a basis for parsimonious cortical
      communication.

PMID- 9040061
TI  - Synchrony in binary-oscillator networks with local couplings.
AB  - Since synchronous oscillations in the visual cortex may be responsible for some
      features of visual scene, many works have been done to study the dynamics of
      oscillatory neural networks. Most of the oscillator network models rely on a
      global connection to reach synchronization. Here we propose a class of neural
      network models based on a simplified binary-oscillator, and find that the neurons
      of networks with local couplings will be in global synchrony under some criteria.

PMID- 9040062
TI  - A competitive activation neural network model for the weighted minimum vertex
      covering.
AB  - We give a generalization of a neural network model originally developed to solve
      the minimum cardinality vertex covering problem, in order to solve the weighted
      version of the problem. The model is governed by a modified activation rule and
      we show that it has some important properties, namely convergence and irredundant
      covers at stable states. We present experimental results that confirm the
      effectiveness of the model.

PMID- 9040063
TI  - Using neural networks to solve the multicast routing problem in packet radio
      networks.
AB  - The primary function of a packet radio network is the efficient transfer of
      information between source and destination nodes using minimal bandwidth and end
      to-end delay. Many researchers have investigated the problem of minimizing the
      end-to-end delay from a single source to a single destination for a variety of
      networks; however, very little work is reported about routing mechanisms for the
      common case where a particular information packet is intended to be sent to more
      than one destination in the network. This is known as multicasting. A simplified
      version of the problem is to ignore the packet delay at each node, then the
      problem becomes one of finding solutions which require the least number of
      transmissions. Determination of an optimal solution is NP-complete meaning that
      suboptimal solutions are frequently tolerated. The problem becomes more rigorous
      if packet delays are included in the network topology. This paper describes a
      practical technique for the computation of optimum or near optimum solutions to
      the multicasting problem with and without packet delay. The method is based on
      the Hopfield neural network and experiment has shown this method to yield near
      optimal solutions while requiring a minimum of CPU time.

PMID- 9040064
TI  - Probabilistic interpretation of feedforward network outputs, with relationships
      to statistical prediction of ordinal quantities.
AB  - Several problems require the estimation of discrete random variables whose values
      can be put in a one-to-one ordered correspondence with a finite subset of the
      natural numbers. This happens whenever quantities are involved that represent
      integer items, or have been quantized on a fixed number of levels, or correspond
      to "graded" linguistic values. Here we propose a correct probabilistic approach
      to such kind of problems that fully exploits all the available prior knowledge
      about their own structure. In spite of the very stringent constraints induced in
      output space, the method can be directly applied to standard feed-forward
      networks while keeping local computation of both outputs and error signals.
      According to these guidelines, we devised a neural implementation of a complex
      image pre-processing algorithm by using very poor resolution on the computing
      elements in the network.

PMID- 9040065
TI  - LIA: a location-independent transformation for ASOCS adaptive algorithm 2.
AB  - Most Artificial Neural Networks (ANNs) have a fixed topology during learning, and
      often suffer from a number of short-comings as a result. ANNs that use dynamic
      topologies have shown the ability to overcome many of these problems. Adaptive
      Self-Organizing Concurrent Systems (ASOCS) are a class of learning models with
      inherently dynamic topologies. This paper introduces Location-Independent
      Transformations (LITs) as a general strategy for implementing learning models
      that use dynamic topologies efficiently in parallel hardware. An LIT creates a
      set of location-independent nodes, where each node computes its part of the
      network output independent of other nodes, using local information. This type of
      transformation allows efficient support for adding and deleting nodes dynamically
      during learning. In particular, this paper presents the Location-Independent
      ASOCS (LIA) model as an LIT for ASOCS Adaptive Algorithm 2. The description of
      LIA gives formal definitions for LIA algorithms. Because LIA implements basic
      ASOCS mechanisms, these definitions provide a formal description of basic ASOCS
      mechanisms in general, in addition to LIA.

PMID- 9040066
TI  - Optimal nonlinear training in the multi-class proximity problem.
AB  - Using a signal-to-noise analysis, the effects of nonlinear modulation of the
      Hebbian learning rule in the multi-class proximity problem are investigated. Both
      random classification and classification provided by a Gaussian and a binary
      teacher are treated. Analytic expressions are derived for the learning and
      generalization rates around an old and a new prototype. For the proximity problem
      with binary inputs but Q'-state outputs, it is shown that the optimal modulation
      is a combination of a hyperbolic tangent and a linear function. As an
      illustration, numerical results are presented for the two-class and the Q' = 3
      multi-class problem.

PMID- 9040088
TI  - Pharmaceutical applications of cyclodextrins. III. Toxicological issues and
      safety evaluation.
AB  - The objective of this review is to summarize recent findings on the safety
      profiles of three natural cyclodextrins (alpha-, beta- and gamma-CDs) and several
      chemically modified CDs. To demonstrate the potential of CDs in pharmaceutical
      formulations, their stability against non-enzymatic and enzymatic degradations in
      various body fluids and tissue homogenates and their pharmacokinetics via
      parenteral, oral, transmucosal, and dermal routes of administration are outlined.
      Furthermore, the bioadaptabilities of CDs, including in vitro cellular
      interactions and in vivo safety profiles, via a variety of administration routes
      are addressed. Finally, the therapeutic potentials of CDs are discussed on the
      basis of their ability to interact with various endogenous and exogenous
      lipophiles or, especially for sulfated CDs, their effects on cellular processes
      mediated by heparin binding growth factors.

PMID- 9040089
TI  - Differences between dynamic and equilibrium surface tension of poly(oxyethylene)
      poly(oxypropylene)-poly(oxyethylene) block copolymer surfactants (poloxamers
      P407, P237, and P338) in aqueous solution.
AB  - Poloxamer surfactants are macromolecules with complex interfacial behavior.
      Although a number of studies of equilibrium surface tension have been published
      recently, there is little information on the diffusion of these large molecules
      to the air-liquid interface. Because most surfactants are used in dynamic
      systems, the diffusion to the surface can be critical in controlling performance.
      In this study a maximum bubble pressure method was used to study dynamic surface
      tension (DST) of Poloxamer P407, P237, and P338, at a range of bubble rates
      (surface age) and concentrations, at either 25 or 35 degrees C. The DST did not
      change at the critical micelle concentration and also did not vary in the same
      manner as the equilibrium surface tension (EST) with respect to temperature. It
      was concluded that DST behavior of the surfactants was most closely related to
      the poly(oxyethylene) content and/or total molecular weight of the surfactants,
      whereas the micellization and hence the EST were more closely related to the
      poly(oxypropylene) content.

PMID- 9040090
TI  - In vitro targeting of antibody-conjugated echogenic liposomes for site-specific
      ultrasonic image enhancement.
AB  - Tissue-specific ultrasonic enhancement can be used for the detection and
      characterization of atherosclerosis. We have previously demonstrated the
      generation of inherently echogenic (acoustically reflective) liposomes solely by
      varying lipid composition and controlling the method of production. In this
      study, echogenic liposomes composed of phosphatidylcholine (PC), 4-(p
      maleimidophenyl) butyryl phosphatidylethanolamine (MPB-PE), phosphatidylglycerol
      (PG), and cholesterol were conjugated to human gamma globulin to determine the
      effect of antibody conjugation on liposomal acoustic reflectivity. The liposomes
      remained highly echogenic following antibody conjugation. Echogenic liposomes
      were also conjugated to rabbit antihuman fibrinogen to study their ability to
      target fibrin. Antibody-conjugated liposomes were targeted to fibrin-coated
      filter paper and slides, thrombi made in vitro, and segments of atheroma in an
      animal model of atherosclerosis. Liposomes were detected by scanning electron
      microscopy, radiolabeling, and imaging with intravascular ultrasound. Electron
      microscopy revealed attachment of antibody-conjugated liposomes to fibrin on
      slides and to the fibrous plaques of the arterial segments, whereas unconjugated
      liposomes did not attach. Similarly, conjugated liposomes did not attach to
      normal arteries, indicating their binding to the arterial segment is directed
      towards a component of the fibrous plaque. Ultrasound imaging of the thrombi
      demonstrated surface attachment of the acoustic conjugated liposomes. 125I
      Labeled liposomes conjugated to rabbit anti-human were targeted to fibrin-coated
      paper. Counting specifically bound radioactivity showed that > 84% of applied
      liposomes remained attached to the fibrin after washing with saline. These
      results demonstrate the potential of acoustically reflective liposomes for site
      specific targeting and acoustic enhancement.

PMID- 9040091
TI  - Radioimmunoassay of meterelin and pharmacokinetics after single injection and
      implant administration in dogs.
AB  - A sensitive and specific radioimmunoassay for a novel luteinizing-hormone
      releasing-hormone (LHRH) agonist, [2-Me-D-Trp6, DesGly10]LHRH ethylamide
      (meterelin), was developed for documenting the pharmacokinetic parameters of this
      peptide following its intravenous (iv) and subcutaneous (sc) administration in
      dogs. The assay was also used for monitoring meterelin in plasma following its
      release from d,l-lactide-glycolide implants in the same species. Rabbit antisera
      generated against [DespyroGlu1] meterelin and conjugated to bovine serum albumin
      with glutaraldehyde showed high specificity, whereas crossreactivity to LHRH and
      its fragments and to analogs with substitutions at residues 6 and 10 was found
      insignificant. The assay was validated in terms of accuracy (recovery range, 94.0
      105.4%), in terms of precision (intra- and interassay variations of 10.0-12.4%
      and 8.6-11.3%, respectively), and in terms of sensitivity (minimum detectable
      dose of 2.7 pg/assay). Following iv acute administration, a biexponential decline
      of plasma meterelin levels was observed, with distribution and elimination half
      lives of 5.9 +/- 2.5 and 106 +/- 22 min, respectively. After sc acute
      administration, the elimination half-life was in the range of 103 to 173 min. The
      systemic clearance (CLT) ranged from 1.6 to 2.6 mL/min/kg, and the volume of
      distribution at steady state (Vdss) varied from 285 to 438 mL/kg. The elimination
      half-life (T1/2 beta), Vdss, and ClT were not significantly different after both
      routes of administration over the 1-100-microgram/kg dose range of peptide
      studied. Castrate levels of testosterone were attained 10 days after sc
      administration of the implant, lasted for up to 247 days, and were well
      correlated with plasma levels of meterelin.

PMID- 9040092
TI  - The hydrophobic propensity of water toward amphiprotic solutes: predicton and
      molecular origin of the aqueous solubility of aliphatic alcohols.
AB  - A quantitative expression of the hydrophobic effect for amphiphilic solutes in
      water is developed in the frame of the nonergodic thermodynamics of mobile order
      in hydrogen-bonded liquids. In the case of aliphatic alcohols, the new expression
      leads to reduction of the hydrophobic propensity of water with respect to that
      exerted towards substances with no hydrogen bonding capacity. The reduction
      originates from the possible insertion of the alcohol molecules in the weakest
      hydrogen bond chain of water; hence, strengthening the hydrogen bonding network
      of water. Combined with the previous solubility model derived from mobile order
      thermodynamics, the new expression allows correct predictions of the solubility
      of 86 liquid and solid branched- and straight-chain alcohols in water at 25
      degrees C, and provides better understanding of their behavior in aqueous
      solution. The model is furthermore applied to the estimation of the aqueous
      solubility of 12 monohydroxysteroids.

PMID- 9040093
TI  - Chemical release from topical formulations across synthetic membranes: infinite
      dose.
AB  - Drug release rates from topical preparations are sometimes measured by monitoring
      the cumulative mass of drug appearing in a receptor solution (MR). If the topical
      formulation and receptor solution are in direct contact, then MR increases
      linearly with square root of t. When a synthetic membrane is placed between the
      topical formulation and receptor solution, drug appearance in the receptor
      solution is delayed and MR is not immediately linear in square root of t. As a
      result, linear regressions of MR with square root of t produce positive values
      for the square root of t-intercept. Here, we mathematically model chemical
      release from an infinite-dose, topical formulation across synthetic membrane to
      quanitiatively determine the physical meaning of the square root of t-intercept.
      To correctly determine drug diffusivity in the topical formulation, the
      experiment must be conducted long enough that MR is linear in square root of t.
      Theoretically based procedures are presented for testing which data should not be
      used in linear regression of MR with square root of t. Theoretical predictions
      are compared with previously published experimental results for ethyl salicylate
      across a poly(dimethylsiloxane) (Silastic) membrane and for hydrocortisone across
      several different synthetic membranes.

PMID- 9040094
TI  - Simultaneous determination of unlabeled and deuterium-labeled indinavir in human
      plasma by high-performance liquid chromatography with tandem mass spectrometric
      detection.
AB  - A method for the simultaneous determination of indinavir and its hexadeuterated
      analog (d6-indinavir) in human plasma is described. Isolation of the analytes and
      internal standard from plasma was achieved via liquid-liquid extraction with
      methyl-t-butyl ether. The analytes were chromatographed under reversed-phase
      conditions on a BDS-Hypersil C8 column. A Sciex API III+ tandem mass spectrometer
      equipped with a turbo ion-spray interface was used as the detector. Multiple
      reaction monitoring using the parent-->product ion combinations of m/z 614-->465,
      620-->471 and 654-->505 were used to quantify indinavir, d6-indinavir, and
      internal standard, respectively. The method was validated, using 1-mL aliquots of
      plasma, in the concentration range in plasma of 1 to 200 ng/mL. Precision of the
      assay, as measured by the coefficient of variation, ranged from 0.9 to 4.3% and
      0.9 to 6.2% for indinavir and d6-indinavir, respectively. Indinavir assay
      accuracy ranged from 95.8 to 105.0% of nominal, whereas the accuracy of the assay
      for d6-indinavir ranged from 97.4 to 104.0% of nominal. The assay was used to
      support a clinical study in which the stable isotope technique was used to
      determine the bioavailability of indinavir.

PMID- 9040095
TI  - Salicylic acid induces changes in the physical properties of model and native
      kidney membranes.
AB  - Salicylic acid (SA) can inhibit the facilitated transport of inorganic sulfate in
      the kidney, placenta, and erythrocytes. One mechanism of this inhibition could
      involve the interaction of SA with membranes, resulting in altered function of
      transporter protein(s) due to changes in membrane fluidity. Such membrane effects
      could result in altered membrane transport and consequently in changes in the
      pharmacokinetics and the therapeutic activity of both xenobiotics and endogenous
      substrates. We investigated the effect of SA on the fluidity of brush border
      membrane (BBM) and basolateral membrane (BLM) isolated from rat kidney and also
      on the physical properties (such as phase transition temperature and fluidity) of
      model membranes by fluorescence polarization and differential scanning
      calorimetry (DSC) techniques. SA decreased the lipid order parameter (S) of BBM
      and BLM membranes in a concentration-dependent manner, indicating that the
      addition of SA makes the membrane more fluid. The fluidizing effect of SA was
      more pronounced than that of benzyl alcohol. Studies were carried out with
      protein-free model membranes composed of dipalmitoylphosphatidylcholine (DPPC) to
      investigate the effects of SA on the bilayer membrane lipids. SA decreased the
      fluorescence polarization of DPH (1,6-diphenyl 1,3,5-hexatriene) incorporated in
      DPPC vesicles. DSC studies demonstrated that SA broadened the phase transition
      temperature of DPPC vesicles and suggested that SA is located in the C1-C8 region
      of the acyl chain. In protein-free model membranes, SA exerted fluidizing effects
      through its incorporation into the cooperative hydrophobic region of the bilayer.
      The perturbation of membrane physical properties induced by SA and its
      hydrophobic localization in the membrane bilayer may be important in the SA
      induced alteration of sulfate membrane transport.

PMID- 9040096
TI  - The effect of surfactants on the rate of decarboxylation of p-aminosalicylic acid
      in acidic aqueous solutions.
AB  - p-Aminosalicylic acid, which exists in four ionic forms and whose decarboxylation
      is well known, was used as a model drug to investigate the effects of surfactants
      with different charges on its stability. The greatest reduction in the rate of
      decarboxylation at 50 degrees C occurred when the charge on the micelles was
      opposite to that of the charge on the drug or when both the drug and the micelle
      had a neutral charge. Thus, at the highest surfactant concentration, 3 or 5%
      (w/v), there was a 59% reduction in the rate at pH 2.68 in the presence of the
      nonionic surfactant polyoxyethylene 24 monocetyl ether, 69% reduction in the rate
      at pH 4.88 in the presence of the cationic surfactant hexadecyl trimethylammonium
      bromide, and a 43% reduction at pH 1.01 in the presence of the anionic surfactant
      sodium cetyl sulfate. The decrease in the rate of decarboxylation was attributed
      to the partitioning of the drug into the micelles, which provided a phase for
      improved stabilization. Partition coefficients and rate constants for
      decarboxylation of the drug inside the micelles were calculated.

PMID- 9040097
TI  - A comparison of phenobarbital and codeine incorporation into pigmented and
      nonpigmented rat hair.
AB  - Drugs and endogenous compounds circulating in the blood may ultimately become
      incorporated into a growing hair shaft. Hair analysis for drugs of abuse is a
      growing field in the area of forensic and clinical toxicology. However, the
      underlying principles that govern drug incorporation into hair are not known. In
      this study, we examined the incorporation of a weak acid, phenobarbital, and a
      weak base, codeine, into Sprague-Dawley (SD) rat hair. Codeine or phenobarbital
      was administered to male SD rats at 40 mg/kg/day for 5 days by intraperitoneal
      (ip) injection. Hair was collected from the back 14 days after beginning the 5
      day dosing protocol and analyzed by gas chromatography/mass spectrometry (GC/MS)
      for codeine and phenobarbital. The time-courses of phenobarbital and codeine in
      plasma were also obtained after a single ip injection (40 mg/kg). Concentrations
      of codeine and phenobarbital in SD hair samples were 0.98 +/- 0.10 and 17.01 +/-
      1.40 ng/mg hair. respectively. The areas under the curve (AUC) of plasma
      concentration versus time for codeine and phenobarbital were 1.58 and 414.50
      micrograms h/microL, respectively. Notwithstanding the greater phenobarbital
      concentrations in hair, when plasma concentrations were considered, codeine was
      apparently incorporated to a 15-fold greater extent than phenobarbital. Because
      hair pigmentation may be important in drug incorporation, the incorporation of
      these two drugs was also studied in Long-Evans (LE; produces both black and white
      hair on the same animal) rats after 40 mg/kg/day of ip drug administration for 5
      days. Hair was collected at the same time as the previous experiment.
      Concentrations of codeine in hair were 44-times greater in pigmented than
      nonpigmented hair from the same animals. In contrast, hair concentrations of
      phenobarbital were identical in both pigmented and nonpigmented hair. These data
      suggest that hair pigmentation greatly affects weak base incorporation but not
      weak acid incorporation into hair. Because hair concentrations of phenobarbital
      are not affected by pigmentation, phenobarbital may be an ideal drug to separate
      out factors other than pigmentation involved in incorporation of drugs into hair.

PMID- 9040098
TI  - Kinetic analysis of the covalent binding of captopril to human serum albumin.
AB  - A simple and direct method using an N-methylpyridinium polymer-based (4VP-Me)
      column for the detection of the human serum albumin (HSA)-captopril (Cp)
      conjugate was developed. By this method, a new peak corresponding to an HSA-Cp
      conjugate was detected in the serum from a patient receiving Cp. The new peak was
      composed of a 1:1 molar ratio of Cp and HSA. Time courses of reversible and
      irreversible binding of Cp to HSA were quite different. The reversible binding
      decreased rapidly, whereas covalent binding increased gradually. A mechanism is
      proposed for the formation of the HSA-Cp conjugate and, based on this mechanism,
      apparent first-order rate constants were calculated. Interestingly, the
      reactivity in serum was approximately 10-fold higher than that obtained for HSA
      solutions. The differences in this reaction between serum and HSA solution might
      be due to the fluctuations in pH as well as the presence of endogenous thiol
      compounds, oxygen, and metal ions in the solutions.

PMID- 9040099
TI  - Effect of alkyl chain length and degree of substitution on the complexation of
      sulfoalkyl ether beta-cyclodextrins with steroids.
AB  - This study was designed to test how the sulfoalkyl ether (SAE) modification of
      beta-cyclodextrin (beta-CD) affects the binding capacity of testosterone and
      progesterone, thereby enhancing their solubility. The SAE-beta-CD derivatives
      contain either sulfopropyl ether (SPE) or sulfobutyl ether (SBE) groups on the 2
      , 3-, and 6-hydroxyl positions of the dextrose moieties. SAE-beta-CDs are a
      mixture of positional and regional isomers containing from one to as many as 12
      SAE groups per CD. The effect of chain length and the degree of substitution on
      complexation behavior was investigated by the phase-solubility method. The
      results were compared with those obtained with beta-CD, where possible, and with
      hydroxypropyl-beta-CD (HP-beta-CD). To determine the effect of degree of
      substitution (DS) on the binding, mixtures of SAE-beta-CDs with multiple
      substitution levels and varying average degrees of substitution were studied as
      well as mixtures of SAE-beta-CDs that contained the same degree of substitution.
      Mixtures that contained SAE-beta-CDs of the same degree of substitution were
      isolated from the multiple substitution level mixtures by ion-exchange
      chromatography and purified for investigation. Unlike the parent beta-CD, linear
      increases in the apparent solubilities of testosterone and progesterone were
      observed, and the binding potentials were comparable to those of beta-CD or
      better. The results demonstrate that the binding potentials of the SAE-beta-CD
      derivatives were dependent on the guest molecule, the degree of substitution, and
      the alkyl ether chain length. Our previous study showed the inhibition of
      complexation by direct sulfonation of the beta-CD. However, in the present work,
      interferences with the charged sulfonate groups were avoided by repositioning
      them away from the cavity. Increasing the degree of substitution assisted in
      complex formation; however, its effects were limited. Reduction of the alkyl
      chain length, as in the case of SPE-beta-CD compared with SBE-beta-CD, decreased
      the complexation potential. This decrease in complexation potential was further
      suppressed with an increase in the number of substituents placed on the CD torus.
      Generally, the binding potential of SAE-beta-CD derivatives increased with
      increasing alkyl chain length. However, placement of more than an optimum number
      of SAE groups on the CD torus resulted in inhibition of complexation.

PMID- 9040100
TI  - Interactions of nonsteroidal antiinflammatory drugs with phospholipids:
      comparison between octanol/buffer partition coefficients and chromatographic
      indexes on immobilized artificial membranes.
AB  - A set of seventeen nonsteroidal antiinflammatory drugs (NSAIDs), consisting of
      structurally unrelated carboxylic acids and piroxicam, was examined by high
      performance liquid chromatography (HPLC) on an immobilized artificial membrane
      (IAM) column that is a solid-phase model of fluid membranes. The chromatographic
      capacity factors extrapolated to 100% aqueous phase (log KWIAM) were compared
      with n-octanol/buffer lipophilicity parameters. The interactions with
      phospholipids were much better predicted from the intrinsic partition
      coefficient, log P, than from the apparent partition value, log D7.4, indicating
      that phospholipids can counteract the influence of electrically charged functions
      of analytes on lipophilic interactions. The log KWIAM and log P values for both
      NSAIDs and structurally unrelated neutral compounds result in unique scale if
      uniquely partition-based mechanisms take place. However, an electrostatic
      repulsion component was observed for the NSAIDs bearing the carboxylic function
      directly linked to the aromatic ring, and for ibuprofen. Hence, the IAM-derived
      scale is distinctive from the one obtained by lipophilic parameters. The IC50
      values on cyclooxygenase 2 (COX-2) in intact cells determined by different
      authors have been successfully correlated with respective IAM parameters, whereas
      no correlation was found with COX-1 activity data. These results suggest that
      membrane affinity may represent an important prerequisite for the specific
      binding NSAIDs/COX-2.

PMID- 9040101
TI  - A kinetic study of phosphate adsorption by boehmite.
AB  - Rates of phosphate adsorption to PT-A (a new type of aluminium oxide hydroxide)
      and ALG (aluminum hydroxide gel) from a pH 3 phosphate solution were measured by
      a batch method. Phosphate uptake progressed mainly by the adsorption mechanism
      for PT-A, but dissolution of aluminum and precipitation of aluminum phosphate
      took place in addition to phosphate adsorption for ALG. The intraparticle
      diffusivities (Dp'S) of phosphate were evaluated from the time courses of
      adsorption using the model of pore diffusion with a Freundlich-type adsorption
      isotherm. The Dp values were approximately 7 x 10(-7) cm2 S-1 for PT-A and 1 x
      10(-6) cm2 s(-1) for ALG. The tortuosity factors calculated from a model of
      parallel plate pore were 5.1 for PT-A and 6.7 for ALG; these values resembled
      those for porous inorganic ion exchangers. The adsorption rates are high enough
      for each of the samples to be utilized as a phosphate adsorbent to prevent
      hyperphosphatemia in patients on chronic dialysis. PT-A is favored as a phosphate
      adsorbent because of its high chemical stability against acid.

PMID- 9040102
TI  - Binding of cyclodextrins to alicyclic and aromatic substrates: complex formation
      of alpha-, beta-, and gamma-cyclodextrins with substituted cyclohexanecarboxylic
      acids and phenylalkanoic acids.
AB  - Complex binding constants of the three native cyclodextrins with seven
      cyclohexane derivatives (all possessing the carboxylic acid group) and with the
      series C6H5(CH2)nCOOH (n = 0 to 4) were measured in aqueous solution at 25
      degrees C by potentiometry and the solubility method. These results, combined
      with literature data, indicate that alpha- and gamma-cyclodextrins bind with
      comparable strength to both the cyclohexyl and phenyl moieties, with beta
      cyclodextrin binding significantly more strongly. These acid series are compared
      with several series CH3(CH2)nX, where X is CH3, COOH, COO-, OH, SO3-, etc., and
      it is concluded that the X group (for X other than methyl) contributes
      appreciably to complex stability, perhaps by means of an extracavity interaction.
      The COOH group provides a further augmentation of complex stability. NMR CIS and
      ROESY results indicate the presence of isomeric complexes in both the cyclohexyl
      and phenylalkanoic series, and clearly demonstrate the existence of intracavity
      inclusion. An NOE study of the alpha-cyclodextrin: cyclohexanecarboxylate system
      provides evidence for inclusion combined with interaction outside (that is, at
      the rim of) the cavity.

PMID- 9040103
TI  - Alteration of pharmacokinetics and nephrotoxicity of cisplatin by alginates.
AB  - This study was undertaken to demonstrate that alginates could form a complex with
      cisplatin and that the pharmacokinetics and nephrotoxicity of cisplatin could be
      altered by this complexation. The complexes were prepared with alginates of mean
      molecular weights of 10000 (AL-1) and 40000 (AL-2). The plasma clearances of
      cisplatin-alginate complexes were significantly reduced when compared with the
      drug alone. Urinary excretion of platinum (Pt) was increased when animals were
      dosed with the cisplatin-AL-1 complex, but not with the cisplatin-AL-2 complex.
      Renal clearance of cisplatin, when administered alone, was more rapid during the
      first 2 h than the rest of the study period (96 h) and was higher than its plasma
      clearance, which is consistent with irreversible binding of cisplatin to plasma
      protein. On the other hand, renal clearance of cisplatin-alginate complexes was
      not highly time dependent, and the values were more similar to those of plasma
      clearance. Complexation of cisplatin with alginates, especially AL-1, inhibited
      the accumulation of Pt in the kidneys and reduced blood urea nitrogen elevation
      by cisplatin. The in vitro antitumor activities against U937, P388, and cisplatin
      resistant P388 (P388/cisplatin) cells were similar among cisplatin and its
      alginate complexes. These studies indicated that the pharmacokinetics and
      nephrotoxicity of cisplatin could be altered through complexation with alginate
      by (1) reducing cisplatin clearance, (2) inhibition of Pt accumulation of in the
      kidneys, and (3) reduction of apparent nephrotoxicity without decrease in in
      vitro antitumor activity.

PMID- 9040104
TI  - Polymorphism of sulindac: isolation and characterization of a new polymorph and
      three new solvates.
AB  - The polymorphism of sulindac was investigated. Two polymorphs (I and II) and a
      new crystalline form (form III) of sulindac were prepared by recrystallization in
      different solvents. In addition, three new pseudopolymorphs (solvates) from
      acetone, chloroform, and benzene were obtained, with each containing 1 mol of
      solvent to 2 mol of sulindac. Different sulindac polymorphs and pseudopolymorphs
      were characterized by X-ray diffractometry, infrared spectroscopy, differential
      scanning calorimetry (DSC), thermogravimetric analysis (TGA), and hot-stage
      microscopy. The transition behavior of the crystalline forms of sulindac, their
      melting points, and their enthalpies were investigated by DSC. The melting of
      form II was observed at 184 degrees C, and form I subsequently recrystallized
      from this melt. Similarly, form III melts at 145 degrees C and then
      recrystallizes to form I. We also investigated the influence of the
      crystallization solvent on sulindac crystal shape.

PMID- 9040105
TI  - Pharmacokinetic-pharmacodynamic modeling of mivacurium in rats.
AB  - The pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the
      neuromuscular blocking agent mivacurium were evaluated separately in two groups
      of rats receiving 0.6 mg kg-1 of mivacurium in a 2.5-min intravenous continuous
      (iv) infusion. The PK parameters for mivacurium were determined in the first
      group. A two-compartment model describes the kinetics of mivacurium in plasma.
      The estimates of the apparent volume of distribution at steady-state and plasma
      clearance [mean(SE)] were 650 (123) mL kg-1 and 9.9 (0.75) mL min-1 kg-1,
      respectively. In the second group, the evoked tibialis anterior muscle tension
      was monitored. The PK parameters derived from the first group were used to
      compute mivacurium plasma concentrations (C) at the times the PD measurements
      were recorded in the second group. The concentration-neuromuscular effect [%
      depression of initial twitch tension (E)] relationship was analyzed by two
      approaches. (1) The relationship of estimated effect site concentrations versus
      E; a sigmoidal Emax model described the effect compartment concentrations versus
      E relationship. The estimate [mean(SE)] of Cess50 (steady-state plasma
      concentration eliciting half of maximum E) was 0.65 (0.01) microgram mL-1. The
      value [mean-(SE)] of Keo (rate constant of equilibration between plasma and
      effect site) was estimated at 0.32 (0.03) min-1. (2) The relationship of
      descending limb C versus E; a sigmoidal Emax model described such relationship.
      The estimate [mean(SE)] of C50 (post-infusion C eliciting half of maximum E) was
      0.57(0.03) microgram mL-1. The PD properties of mivacurium were also evaluated in
      another two groups of animals receiving either 5- or 10-min continuous iv
      infusion; PK and PD parameters obtained from the 2.5-min infusion experiments
      were used to predict the time course of E in the groups receiving 0.6 mg kg-1 of
      mivacurium in 5- and 10-min infusions; simulations using the estimated parameters
      adequately describe the time course of E in those groups. The effect of
      mivacurium on the mean arterial blood pressure (MAP) was also investigated; a 10%
      nonsignificant decrease (p > 0.05) in MAP was found in all groups.

PMID- 9040106
TI  - Biomembrane permeation of nicotine: mechanistic studies with porcine mucosae and
      skin.
AB  - In the present study, the permeation and partitioning of nicotine as a function
      of pH was investigated with various regions of skin and absorptive mucosae that
      were freshly excised from domestic pigs. As an ionizable compound (pKa values of
      3.04 and 7.84), nicotine in solutions of different pH values provides a model for
      determining the influence of the charge status of a molecule on permeation. The
      permeation of nicotine across porcine mucosae and skin followed zero-order
      kinetics. The rate of permeation was dependent on donor solution pH and increased
      exponentially as the pH increased. With an exception of the nasal mucosa, which
      showed similar permeabilities for all species of nicotine, the permeability of
      nicotine across various skin and mucosal specimens was significantly higher (p <
      0.001) for the un-ionized species (NN) than for the ionized species (NNH+,
      NH+NH+). It was also seen that un-ionized nicotine molecules were more permeable
      through absorptive mucosae (nasal, buccal, sublingual, and gingival) than through
      skin (abdominal, dorsal, thigh, and ear pinna). Partition studies were performed
      and the results further confirmed that biomembrane permeation of nicotine follows
      the pH-partition theory.

PMID- 9040107
TI  - Characterization of pharmaceutical solvates by combined thermogravimetric and
      infrared analysis.
AB  - The combined physical analytical technique of thermogravimetric and infrared
      analysis (TG/IR) is described for the investigation of pharmaceutical solids.
      TG/IR provides an unequivocal identification of the volatile content of a
      pharmaceutical solid. In the case of pharmaceutical solvates, TG/IR provides
      identification of the evolved gas from the crystalline solid. Variable
      temperature X-ray diffraction and differential scanning calorimetry techniques
      provide the required information to ascertain whether the evolved gas was due to
      a solvent incorporated into the crystal lattice or physically adsorbed onto the
      solid. This work illustrates three examples of TG/IR as utilized in a
      multidisciplinary approach to the physical characterization of pharmaceutical
      solids.

PMID- 9040108
TI  - A novel rapid throughput phototolerance screen in mice.
AB  - A relatively simple, rapid throughput phototolerance screen in small animals
      would be very useful in early drug development. It could prioritize or select
      potential lead compounds from among a number of analogs with similar biological
      activities. This study describes an in vivo mouse phototolerance screen
      established for that purpose. It also reports phototolerance data with standard
      reference drugs obtained using this screen.

PMID- 9040109
TI  - A new method of measuring renal function in conscious rats without the use of
      radioisotopes.
AB  - The purpose of the current experiment was to develop fast and accurate assays for
      measuring glomerular filtration rate (GFR) and effective renal plasma flow
      (ERPF). An enzymatic method was developed for the determination of inulin, and a
      colorimetric method was developed for determination of p-aminohippurate (PAH) in
      the plasma and urine of rats. These assays are easily automated and do not
      require the use of radioisotopes or corrosive chemicals. Glomerular filtration
      rate was measured by the clearance of inulin, and effective renal plasma flow was
      measured by the clearance of PAH. Blood pressure, heart rate, and renal function
      (urine volume, electrolytes, GFR, and ERPF) were measured in conscious rats for
      1.5 h prior to drug treatment and for 3 h after treatment. Baseline renal
      function was compared to historical data. Acute changes in GFR and ERPF following
      administration of the vasoconstrictor peptide endothelin-1 (ET-1) were accurately
      measured with results similar to those obtained with older methodologies. These
      new methods offer many advantages over previously described methods by
      eliminating the use of radioisotopes and harsh chemicals. In addition, these
      methods can be used with an automated instrument with high accuracy and
      precision. Therefore, these new methods can be used to accurately determine GFR
      and ERPF and are sensitive enough to detect acute changes in GFR and ERPF in
      conscious animals.

PMID- 9040111
TI  - Quantification of rate-dependent effects of verapamil, diltiazem, and digoxin on
      atrioventricular conduction.
AB  - The calcium channel blocking agents, verapamil and diltiazem, and the digitalis
      compound, digoxin, caused drug specific rate-dependent changes of the
      atrioventricular conduction time (AVCT). The purpose of this study was to
      investigate this rate adaptation of the AVCT in isolated guinea pig hearts
      perfused by the method of Langendorff to get an insight in drug-specific binding
      kinetic to the respective channel. In the presence of 10 nM verapamil, 30 nM
      diltiazem, or 0.6 nM digoxin, the atrioventricular conduction time was prolonged
      to a comparable degree during sinus rhythm. The drug-specific time constant,
      characterizing the rate-dependent adaptation of the AVCT, in the presence of a
      substance was comparable if evaluated after abruptly changing the heart rate from
      the pacing cycle length of 240 ms to 180 ms (tau-on) or from 180 to 240 ms (tau
      off). The adaptation of the AVCT in the presence of verapamil (tau-on = 178 +/-
      45 beats, tau-off = 125 +/- 33 beats, mean +/- SEM) was more pronounced than in
      the presence of digoxin (tau-on = 144 +/- 24 beats, tau-off = 98 +/- 15 beats) or
      diltiazem (tau-on = 70 +/- 11 beats, tau-off = 98 +/- 15 beats). In conclusion,
      the differences in the rate adaptation of the AVCT may be explained by the drug
      specific association and dissociation kinetic to the calcium channel, slow in the
      case of verapamil, and fast in the case of dilitiazem, whereas this phenomenon in
      the presence of digoxin may be explained by its direct effects on passive
      membrane properties.

PMID- 9040110
TI  - Possible use of excretion of tubular epithelial cells for the study of the
      nephrotoxic effect of xenobiotics.
AB  - The method of determination of the minute excretion of tubular epithelial cells
      renders it possible to investigate the course of the nephrotoxic effect of the
      toxin by the influence of which excretion of tubular round epithelial cells is
      increased. The nephrotoxic effect of repeated administration of amphotericin B (1
      mg/kg, i.v.), which produced up to 12-fold increases in the number of excreted
      epithelial cells, was examined. Repeated administration of cyclosporin A (45 and
      56 mg/kg, p.o.) produced up to 23-fold increases in the number of excreted
      epithelial cells. The degree of excretion of epithelial cells after
      administration of both drugs was compared with the urinary excretion of alanine
      aminopeptidase and N-acetyl-beta-D-glucosaminidase, which indicated
      nephrotoxicity in amphotericin B and cyclosporin A with a lower sensitivity than
      the increase in the excretion of epithelial cells. In the experiment with
      cyclosporin A, urinary excretion of epithelial cells was further correlated with
      renal functional tests (clearance of polyfructosan and hippurate.

PMID- 9040112
TI  - A modified device for the differentiated study of intestinal transfer in isolated
      intestinal segments from mice and suckling rats in vitro.
AB  - An increasing number of mice with genetic variation of intestinal transfer
      properties is becoming available. A luminal perfusion system for small intestinal
      segments, therefore, was adapted for the use in mice and rat pups to investigate
      longitudinal differences in intestinal drug and toxin transfer and to explore the
      adaptation of transfer properties during maturation under standardized conditions
      in vitro. At present, cell cultures are inadequate for this goal. The perfusator
      consists of an upper reservoir and a lower moist chamber to accommodate the
      intestinal segment. The luminal perfusion fluid is oxygenized and circulated by a
      gas lift. It is directed through the segment by two three-way taps. For safe and
      easy decontamination of radioactive substrates, the system is made entirely of
      glass. To perfuse fragile segments from small animals such as mice and rat pups
      in vitro, the perfusion pressure had to be reduced to 15 cm H2O column.
      Therefore, the design of the perfusator was changed, and the gas lift and the
      three-way taps were moved to the side. With segments from adult rats, the
      modified perfusor yielded the same transfer data for 59Fe, glucose, and water as
      did the standard device. Experiments with proximal and distal segments from mice
      and rat pups showed a longitudinal pattern of adaptation during maturation as
      well as due to iron deficiency that was in accordance with expectations
      extrapolated from literature.

PMID- 9040113
TI  - Presence of paf-acether in human blood after thin-layer chromatography, but not
      after high-performance liquid chromatography purification.
AB  - After HPLC purification of human blood extracts, paf-acether (paf) was found
      exclusively as a lipoprotein-bound compound (lipopaf), whereas free-paf was
      absent. When the same samples (or lipopaf recovered from HPLC) were purified by
      TLC, both free-paf and lipopaf were detected. The free-paf detected in blood
      samples could thus result from lipopaf dissociation during TLC purification.

PMID- 9040114
TI  - Continuous intraocular pressure measurement by telemetry in alpha-chymotrypsin
      induced glaucoma model in the rabbit: effects of timolol, dorzolamide, and
      epinephrine.
AB  - The aim of this study was to set-up and validate the use of a radio-telemetry
      system in order to record IOP in chronic ocular hypertensive animals. The
      transmitter of a miniaturized radio-telemetry system was implanted in rabbits,
      and its catheter was tunnelled subcutaneously to the superior conjunctival sac
      and inserted into the midvitreous. Implantation was performed in chronic ocular
      hypertensive rabbits induced by an injection of alpha-chymotrypsin into the
      posterior chamber of the eye. The effects of 0.5% timolol maleate, 2% dorzolamide
      hydrochloride and 1% epinephrine were assessed and compared after topical
      administration in this model. Implanted radio-telemetric system into the vitreous
      allowed IOP measurement for more than 6 months. In this study, circadian IOP
      kinetic profiles were monitored in all animals over 24 h for 3 weeks. Timolol
      maleate was found significantly potent in reducing IOP, while changes depended on
      the nyctemeral period. Dorzolamide hydrochloride induced a very large IOP
      reduction and was found to be also well effective at night. We evidenced a
      biphasic time-dependent effect after topical epinephrine, with a long lasting IOP
      increase occurring after the administration. This change was found to be related
      to side effects resulting from a poor ocular tolerance of this drug in the
      rabbit, leading to either a complete eye closure or a higher blinking rate. By
      using our method, we confirmed the pressure pulses and undershoots occurring
      during blinking. Radio-telemetry in chronic glaucoma rabbits appears as a refined
      method to assess anti-glaucoma drug activity, 24 hours a day, for long-term
      periods in unrestrained animals, while also providing information on the ocular
      side effects of eye drops.

PMID- 9040115
TI  - Endogenous opioid systems and alcohol addiction.
AB  - Alcohol exerts numerous pharmacological effects through its interaction with
      various neurotransmitters and neuromodulators. Among the latter, the endogenous
      opioids play a key role in the rewarding (addictive) properties of ethanol. Three
      types of opioid receptors (mu, delta and kappa) represent the respective targets
      of the major opioid peptides (beta-endorphin, enkephalins and dynorphins,
      respectively). The rewarding (reinforcing) properties of mu- and delta-receptor
      ligands are brought by activation of the mesolimbic dopamine system which ascends
      from the ventral tegmentum of the midbrain (VTA) to rostral structures; of these,
      the nucleus accumbens (NAC) is of particular importance in drug addiction. In
      contrast, dysphoria results from activation of kappa-receptors. The neurochemical
      manifestations of these opposing effects are, respectively, increases and
      decreases in dopamine release in the NAC. Several lines of evidence indicate that
      alcohol interferes with endogenous opioid mechanisms which are closely linked
      with dopamine transmission in the mesolimbic pathway. The view that condensation
      products of dopamine and alcohol-derived aldehyde (tetrahydroisoquinolines) play
      a role remains controversial. There is, however, much information on the direct
      (acute and chronic) effects of alcohol on the binding properties of opioid
      receptors, as well as modulation of opioid peptide synthesis and secretion (e.g.
      a suggested increase in beta-endorphin release). In view of the reinforcing
      properties of alcohol, it is relevant to consider behavioural studies involving
      alcohol self-administration in rodents and primates. Low doses of morphine have
      been found to increase, and higher doses of the opiate to decrease, alcohol
      consumption. Conversely, opioid antagonists such as naloxone and naltrexone
      (which bind to non-selectively opioid receptors) have been shown to decrease
      alcohol consumption under various experimental conditions. Similar results have
      been reported when selective mu- or delta-receptor antagonists are administered.
      Results obtained in genetic models of high preference for alcohol also support
      the view that alcohol intake depends on the activity of the endogenous opioid
      reward system and that alcohol consumption may serve to compensate for inherent
      deficits in this system. One hypothetical model proposes that reward results from
      activation of mu-opioid receptors in the VTA and/or delta-receptor in the NAC;
      both these nuclei are targets of endogenous beta-endorphin. It is suggested that
      alcohol interferes with this reward pathway either directly or indirectly. The
      available experimental data accord well with those obtained from clinical studies
      which opioid antagonists have been used to prevent relapse in alcoholics.
      Conceptual considerations concerning communalities between various forms of
      addictions are also discussed in this review.

PMID- 9040116
TI  - The role of mesolimbic and nigrostriatal dopamine in latent inhibition as
      measured with the conditioned taste aversion paradigm.
AB  - Repeatedly presenting a non-reinforced stimulus normally retards conditioning to
      this stimulus when it is coupled to a reinforcer. This phenomenon is called
      latent inhibition. Since latent inhibition is disturbed after systemic
      administration of amphetamine, the present study investigated the role of the
      mesolimbic and nigrostriatal dopamine terminal fields in latent inhibition using
      a conditioned taste aversion (CTA) paradigm. In this paradigm, a 5% sucrose
      solution was used as the test stimulus and lithium chloride (LiCl) as the CTA
      inducing drug. The degree of CTA was assessed by measuring the sucrose preference
      in a two-bottle sucrose/water choice paradigm 24 h after the LiCl injection.
      Since conditioned taste aversion has so far not been used to evaluate the role of
      dopamine in latent inhibition, we first studied the effects of systemic
      application of amphetamine. The results show that intraperitoneal injections of
      0.25 or 0.5 mg/kg d-amphetamine sulphate (given at preexposure and conditioning)
      significantly disrupted latent inhibition, by selectively reducing sucrose
      preference in the preexposed group. This could not be attributed to a reduced
      sucrose intake during preexposure or to a conditioned taste aversion effect of
      amphetamine itself. In experiment 2 local bilateral administration of 10
      micrograms/0.5 microliter amphetamine into the nucleus accumbens or the dorsal
      striatum was given in the pre-exposed and the conditioning phase, after which the
      rats were allowed to drink for a fixed period of time. The results show a
      significant reduction in latent inhibition after intrastriatal, but not after
      intra-accumbens injections of amphetamine. Intra-accumbens injections of
      amphetamine, however, significantly reduced fluid intake during preexposure and
      conditioning. In experiment 3, we therefore repeated this experiment, but allowed
      the animals to drink only a restricted amount of liquid during preexposure and
      conditioning. Again the results show a disruption of latent inhibition after
      intrastriatal, but not intra-accumbens injection of amphetamine. These
      experiments emphasize the importance of the nigrostriatal dopamine system in the
      disruption of latent inhibition, at least when using the conditioned taste
      aversion paradigm. A possible mechanism by which the dorsal striatum might
      influence latent inhibition is discussed.

PMID- 9040117
TI  - Ontogeny of the behavioral response to dopamine agonists after chronic cocaine.
AB  - The behavioral response to separate and combined administration of dopamine D1
      and D2 receptor agonists was assessed acutely and after chronic cocaine exposure
      (30 mg/kg s.c. b.i.d. for 5 days) in infant (PND11) and weanling (PND20) rats. In
      infants, quinpirole (quin) and SKF-38393 (SKF) elevated locomotion, mouthing and
      sniffing acutely. Rearing was increased and mouthing decreased by decreased by
      combined administration. In weanlings, quin increased by locomotion, mouthing and
      sniffing in weanlings, while SKF increased only mouthing. SKF inhibited quin
      induced rearing and locomotion. Infants treated chronically with cocaine showed
      sensitized quin- and quin/SKF-induced locomotion and quin/SKF stimulated rearing
      and sniffing. In weanlings, locomotion was sensitized with all drug combinations,
      and rearing with SKF alone. These results indicate a developmental progression in
      the psychopharmacological response to dopamine receptor stimulation. While both
      D1 and D2 receptors are active in infants, the full complement of acute responses
      and complete capacity for sensitization develop later.

PMID- 9040118
TI  - The interaction of cocaine and alcohol on schedule-controlled responding.
AB  - Within a number of physiological preparations, the effects of alcohol and cocaine
      in combination are reported to be greater than the effects of either drug given
      alone. Little has been reported, however, on the behavioral effects of the
      interaction. The present study investigated this issue by assessing the effects
      of cocaine and alcohol (alone and in combination) on schedule-controlled
      responding. Specifically, rats were trained to respond on an FR20 schedule for a
      water reinforcer. They were then administered cumulative doses of cocaine or
      alcohol. Following this, subjects were administered ineffective doses of alcohol
      prior to further dose-response assessments with cocaine and with ineffective
      doses of cocaine prior to further dose-response assessments with alcohol. Cocaine
      and alcohol alone produced dose-related decreases in responding. Furthermore, the
      dose-response function for cocaine was shifted to the left by alcohol and the
      dose-response function for alcohol was shifted to the left by cocaine. An
      isobolographic analysis revealed that the interaction between cocaine and alcohol
      was additive in nature. The possible bases for the interaction (e.g., changes in
      cocaine pharmacokinetics by alcohol and the formation of cocaethylene following
      co-administration of cocaine and alcohol) were discussed.

PMID- 9040119
TI  - Effect of ethanol on sustained attention in rats.
AB  - Acute exposure to ethanol produces deficits in sustained attention in humans, but
      these attentional deficits have not been modeled in animals. In this study, an
      operant task was used to investigate the effects of low and moderate doses of
      ethanol on sustained attention in rats. Performance on a two-choice reaction time
      task over a 1-h session was assessed immediately following administration of
      ethanol (0.0, 0.5, 0.75, 1.0 and 1.5 g/kg i.p.). Each rat was required to respond
      to a light stimulus of variable duration (20, 100, and 500 ms) occurring at one
      of two locations. Under control and saline conditions, increases in stimulus
      length systemically increased choice accuracy and decreased reaction time.
      Ethanol produced a dose-dependent decrease in choice accuracy that interacted
      with time, with an initial impairment that was stimulus length-dependent followed
      by a general vigilance decrement. The data demonstrate that ethanol impaired the
      ability of rats to direct and sustain attention to brief, infrequent stimuli, and
      provide a model for further investigations into the underlying neurobiological
      mechanisms for ethanol-induced attentional deficits.

PMID- 9040120
TI  - Symmetrical effects of amphetamine and alpha-flupenthixol on conditioned
      punishment and conditioned reinforcement: contrasts with midazolam.
AB  - In a test of conditioned punishment, saline-treated controls showed a moderate
      bias in responding away from a lever producing a response-contingent auditory
      conditioned stimulus (CS) that had been paired with mild footshock during
      training and towards a lever producing a neutral auditory CS. Systemic treatment
      with the indirect dopamine (DA) agonist amphetamine (0.25-1.0 mg/kg) produced a
      dose-dependent increase in the punishing effect of the aversive CS, whilst
      responding on the neutral CS lever was unchanged. Treatment with the dopamine
      receptor antagonist alpha-flupenthixol (0.125, 0.25 mg/kg) decreased the efficacy
      of the punishing CS, but again left responding on the neutral lever unchanged.
      The benzodiazepine midazolam (0.1, 0.3 mg/kg) had a similar effect to alpha
      flupenthixol, but treated animals showed a preference for the aversive CS.
      Parallel results were observed with amphetamine (0.25 mg/kg) and alpha
      flupenthixol (0.125, 0.25 mg/kg) in a matched test of positive conditioned
      reinforcement, with amphetamine enhancing, and alpha-flupenthixol reducing, the
      efficacy of the CS paired with food. Midazolam treatment (0.1-1.0 mg/kg) had no
      effect on the reinforcing impact of an appetitive CS. Thus dopaminergic agents
      modulate the behavioural impact of both appetitively and aversively motivated
      conditioned stimuli on instrumental performance, whilst the benzodiazepine
      midazolam has a selective impact on aversively-motivated stimuli that is
      qualitatively distinct from that of the dopaminergic antagonist alpha
      flupenthixol.

PMID- 9040121
TI  - Ontogeny of dopamine agonist-induced sensitization: role of NMDA receptors.
AB  - In contrast to adults, preweanling rats exhibit behavioral sensitization for only
      a few days after cessation of dopamine (DA) agonist treatment. The reasons for
      this ontogenetic difference are uncertain, but maturational changes in the N
      methyl-D-aspartate (NMDA) receptor may be responsible, since stimulation of these
      receptors is necessary for the development of DA agonist-induced sensitization in
      adult rats. The purpose of the present study was to examine the relationship
      between NMDA receptor functioning and DA agonist-induced sensitization during the
      preweanling period. To that end, 17-day-old rats were injected (i.p.) on 4
      consecutive days with saline or 0.3 mg/kg dizocilpine (a non-competitive NMDA
      receptor antagonist) followed, 30 min later, by an injection of saline, 2.5 mg/kg
      amphetamine (an indirect DA agonist), or 1.0 mg/kg NPA (a direct DA agonist).
      Sensitization was tested 2 days later (i.e., at 22 days of age), with rats
      receiving a challenge injection of saline, amphetamine, NPA, or dizocilpine.
      Results showed that the NMDA antagonist had adult-like effects on the behavioral
      sensitization of preweanling rats, as amphetamine- and NPA-induced sensitization
      were eliminated by dizocilpine pretreatment. When given alone, dizocilpine
      substantially increased the locomotor activity (i.e., line-crosses) of
      preweanling rats, an effect that became sensitized with repeated drug treatment.
      Lastly, preweanling rats already sensitized to dizocilpine did not exhibit cross
      sensitization to amphetamine or NPA. Thus, with few exceptions, NMDA receptor
      stimulation appears to modulate sensitization in a similar fashion across
      ontogeny. This finding suggests that maturational differences in the NMDA
      receptor system are not responsible for the lack of long-term sensitization in
      the younger animal.

PMID- 9040122
TI  - Impairments produced by amphetamine and stress on memory storage are reduced
      following a chronic stressful experience.
AB  - Post-training administration of the psycho-stimulant, amphetamine or post-trial
      exposure to restraint stress impaired retention of an inhibitory avoidance
      response in DBA/2 (DBA) mice. The effect of amphetamine was dose-dependent (1-3
      mg/kg) whilst the effect of stress depended on restraint duration (15, 30, or 60
      min). Both effects on retention performance appeared to be due to an effect on
      memory consolidation. In fact, they were observed when the drug and the stressor
      were experienced at short, but not long, periods of time after training, which is
      when the memory trace is susceptible to modulation. Moreover, these effects could
      not be ascribed to a rewarding or non-specific action of the two treatments on
      retention performance, as the latencies during the retention test of those mice
      that had not received a footshock during the training, were not affected by the
      post-training treatments. Administration of either D1 (SCH23390) or D2 [(-)
      sulpiride] dopamine (DA) receptor against prior to amphetamine injection or
      stress exposure antagonized the impairing effects of both treatments. These data
      indicate that brain dopamine was involved in both cases. Finally, when mice were
      food restricted for 13 days than allowed free access to food for 24 h before
      training, either the effects of amphetamine or restraint stress were reduced.
      Food restricted mice did not differ from control for stepthrough latencies either
      on the training or the test days, indicating the absence of amnesic or otherwise
      impairing effects of the experimental procedure per se. Instead, the results
      indicated hyposensitization to the effects of amphetamine and stress on memory
      consolidation in food restricted animals.

PMID- 9040123
TI  - NNC-19-1228 and NNC 22-0031, novel neuroleptics with a "mesolimbic-selective"
      behavioral profile.
AB  - NNC 19-1228 [1-(3(6-methylenedioxyphenylcarbamoyloxy) propyl)-4-(6-fluoro-1,2
      benzisoxazol-3-yl) piperidine] and NNC 22-0031 [4-(6-fluoro-1,2-benzisoxazol-3
      yl) -1-(3-(3,4-methylenedioxyphenylcarbamoyloxy) propyl)piperidine] are newly
      developed compounds with an in vitro pharmacologic profile similar to that of
      clozapine, i.e., mixed dopamine (DA), 5-hydroxytryptamine (5-HT)2 and alpha 1
      adrenergic antagonist action. In pharmacological experiments in mice, the
      compounds inhibited DA D2 receptor binding in vivo at doses that produced only
      moderate antagonism of methylphenidate (MPD)-induced stereotyped gnawing.
      However, the compounds were markedly more potent in blocking MPD-induced
      motility, a model which showed a high degree of sensitivity to alpha 1-adrenergic
      antagonism, but not 5-HT2 antagonism. In rats, the NNC-compounds blocked
      conditioned avoidance responding and attenuated the discriminative stimulus
      effects of amphetamine, but failed to induce catalepsy. These results are
      discussed in terms of adrenergic, serotonergic and dopaminergic interactions
      which suggest that the NNC compounds may act as DA antagonists with mesolimbic
      selectivity, and thus may have efficacy as antipsychotics without coincident
      extrapyramidal side effects.

PMID- 9040124
TI  - Sumatriptan decreases food intake and increases plasma growth hormone in healthy
      women.
AB  - We studied the effect of the 5-HT1B/ID receptor agonist sumatriptan (6 mg s.c.)
      on plasma growth hormone and prolactin and food intake in 15 healthy female
      subjects using a double-blind, placebo-controlled, cross-over design. Sumatriptan
      significantly elevated plasma growth hormone but did not alter plasma prolactin.
      Sumatriptan also significantly lowered total food intake in a buffet meal,
      particularly decreasing the intake of fat. Our results indicate that 5-HT1B/ID
      receptors may be involved in the regulation of food intake in humans. In
      addition, while activation of 5-HT1B/ID receptors stimulates growth hormone
      release in both men and women, sumatriptan lowers plasma prolactin only in men,
      suggesting sex differences in the 5-HT regulation of prolactin release.

PMID- 9040125
TI  - Chronic, low-level exposure to diisopropylfluorophosphate causes protracted
      impairment of spatial navigation learning.
AB  - Chronic, low-level exposure to cholinesterase inhibitor organophosphate (OP)
      insecticides or chemical warfare agents produces abnormalities in CNS
      acetylcholine (ACh) function, and in humans, may be associated with impaired
      cognitive function as well after withdrawal from such exposure. The purpose of
      the present study was to identify the severity of impairment in spatial learning
      of rats following protracted withdrawal from chronic, low-level exposure to the
      OP agent diisopropylfluorophosphate (DFP). Assessment of spatial learning began
      either 3 or 17 days after completion of a 14-day DFP treatment regimen (50, 250,
      or 500 micrograms/kg). During the 14-day treatment regimen, spontaneous activity
      and olfactory behaviors were suppressed, effects which subsided with repeated
      exposure to the 250 micrograms/kg dose regimen. In contrast, both behaviors were
      stimulated by exposure to the 50 micrograms/kg dose regimen, as was body weight
      gain. Performance of the spatial test of working memory was impaired for up to 21
      days after withdrawal from treatment with a 250 micrograms/kg dose of DFP. AChE
      activity in the frontal cortex and hippocampus was suppressed to 42.58% and
      50.35% of control levels, respectively, 3 days after completion of the DFP (250
      micrograms/kg) treatment regimen. By 7 days after withdrawal from treatment, AChE
      activity in the cortex and hippocampus had recovered to 81.87% and 64.61% of
      control levels, respectively. These levels represent increases in activity of
      39.29% and 14.26% in these regions, as compared to AChE activity in 3 days after
      DFP withdrawal. By 21 days after withdrawal from treatment, AChE in both brain
      regions had recovered to levels similar to those of controls. Chronic, low-level
      OP exposure, therefore, produces protracted impairment of working memory after
      drug withdrawal that is not associated with continued suppression of AChE
      activity. This impairment may, however, be associated with a decreased rate of
      AChE recovery in the hippocampus, relative to the cortex. This decreased rate of
      enzyme recovery may contribute to hippocampal toxicity underlying protracted
      impairment of working memory.

PMID- 9040126
TI  - Biochemical studies support the assumption that dopamine plays a minor role in
      the EEG effects of nicotine.
AB  - In a previous study, it was shown that a moderate dose of nicotine (0.2 mg/kg
      s.c.) produced a desynchronization in the EEG and a decrease of power which was
      not antagonized by blockade of D1-like dopamine receptors, although this EEG
      pattern seemed to be characteristic for activation of D1-like rather than D2-like
      receptors. This seemed surprising, since nicotine is known to enhance
      dopaminergic neurotransmission in the basal ganglia. Since there is a strong
      reciprocal connection between the cortex and the striatum, dopaminergic effects
      on the striatum should lead to alterations in the cortical EEG. Therefore, the
      release of dopamine was studied in the striatum by using microdialysis in awake
      rats, and in parallel studies, the EEG was studied for administration of a larger
      dose of nicotine (0.4 mg/kg s.c.). This is a dose which does not induce toxic
      side effects. This dose produced a desynchronization in the EEG and a release of
      power. The increase in extracellular dopamine in the striatum was very moderate
      (by about 30%) and of shorter duration than the EEG effect. Therefore, activation
      of striatal dopaminergic neurotransmission does not seem to be relevant for the
      EEG effect studied.

PMID- 9040137
TI  - Does osteolysis of the distal clavicle occur following spinal cord injury?
AB  - OBJECTIVE: To determine whether there is an association between spinal cord
      injury and "atraumatic" osteolysis of the distal clavicle. PATIENTS AND DESIGN:
      Seventy-seven consecutive spinal cord injury patients without upper extremity
      injuries were studied. Of these, 39 each had a pair of chest radiographs--one at
      admission and one at least 1 month later--which included both acromioclavicular
      joints. Each radiograph was evaluated by two independent musculoskeletal
      radiologists, who were masked as to which radiograph was the baseline. RESULTS:
      Ten of 76 acromioclavicular joints demonstrated osteolysis of the distal
      clavicle: three bilateral, three left side only, and one right side only. There
      was one case in which the admission radiograph was read as osteolysis but
      reverted to normal at 35 months follow-up. CONCLUSION: There is an apparent
      association between spinal cord injury and osteolysis of the distal clavicle.

PMID- 9040136
TI  - MR imaging of musculoskeletal tumors and tumor mimickers with intravenous
      gadolinium: experience with 242 patients.
AB  - PURPOSE: This pictorial essay reviews our experience with MR scans with
      gadolinium in patients with musculoskeletal tumors and tumor mimickers. DESIGN:
      Review of 242 MR scans obtained in the initial evaluation of a possible primary
      musculoskeletal neoplasm. All scans included a T1-weighted, fat-suppressed
      sequence following intravenous administration of gadolinium. RESULTS: MR scans
      with gadolinium did not contribute to differential diagnosis or patient
      management in 89% of the patients in this series. However, intravenous gadolinium
      did assist in guiding the biopsy of bulky lesions and evaluating treated tumor
      beds for possible recurrence. MR scans with gadolinium were sometimes helpful
      when the differential diagnosis included synovitis, Morton's neuroma or
      intramuscular myxoma, and when it was important to differentiate cystic from
      solid lesions. CONCLUSIONS: Routine use of gadolinium in every initial MR
      examination of a possible musculoskeletal mass is not warranted. However, there
      are appropriate selected indications for gadolinium administration as outlined
      above.

PMID- 9040138
TI  - Natural course of erosive arthropathy of the hand in patients undergoing
      hemodialysis.
AB  - OBJECTIVE: To assess the radiographic features of erosive arthropathy of the
      hands occurring in patients undergoing hemodialysis, and its relationship with
      metabolic abnormalities. PATIENTS AND DESIGN: A retrospective study of hand
      radiographs of 80 patients on maintenance hemodialysis was performed with the aim
      of detecting erosive arthropathy. RESULTS AND CONCLUSIONS: Ten patients showed
      erosive arthropathy of the hands with a predilection for distal interphalangeal
      joints. The first joint abnormality was joint space narrowing with or without
      erosion. The mean duration of hemodialysis was 5 years (range 1-15 years). The
      development of arthropathy could not be related to a metabolic factor. The
      pathogenesis of arthropathy of the hands is possibly multifactorial, accounting
      for the disparate descriptions of the radiographic features in the literature.

PMID- 9040139
TI  - C2-3 facet joint "pseudo-fusion": anatomic basis of a normal variant.
AB  - OBJECTIVE: To identify the anatomic basis for apparent C2-3 facet joint fusion
      (pseudo-fusion) on lateral cervical spine radiographs. DESIGN AND PATIENTS: The
      studies of 81 consecutive blunt trauma patients who had both plain radiographs
      and a CT scan of the upper cervical spine were reviewed. The C2-3 facet joints
      were evaluated on lateral cervical spine radiographs and graded "normal"
      (category 1), "indistinct" (category 2), or "fused" (category 3), relative to the
      C3-4 level. The accompanying CT scans were reviewed for the presence of fusion
      and the angle of orientation of the facet joints relative to the axial and
      coronal planes. RESULTS: In category 1 ("normal"), the C2-3 facet joints were
      oriented nearly parallel to the true coronal and axial plane. In category 2
      ("indistinct"), both the C2-3 facet joints were oriented obliquely to the true
      coronal and axial planes. In category 3 ("fused"), the C2-3 facet joints were
      also oriented obliquely, but at a steeper angle than in category 2. Head
      tilt/rotation caused a change in category rating in 5 of 81 cases (6.2%).
      CONCLUSION: The appearance of C2-3 facet joint fusion (pseudo-fusion) on lateral
      cervical spine radiographs may be a normal anatomic variant. This "pseudo-fusion"
      is due to the oblique orientation of these facet joints relative to the X-ray
      beam and is usually unaffected by patient position.

PMID- 9040140
TI  - Os acromiale: evaluation of markers for identification on sagittal and coronal
      oblique MR images.
AB  - An os acromiale is a developmental abnormality of ossification involving the
      anterior acromion which may contribute to impingement and rotator cuff disease.
      When axial MR sections do not include the acromioclavicular joint, the diagnosis
      of this often subtle abnormality will rest on its recognition on oblique and
      coronal and sagittal images where it mimics the acromioclavicular joint. The
      identification of this anomaly is important as it frequently alters the type of
      surgical procedure utilized in symptomatic patients. We evaluate several imaging
      features which may be used to diagnose an os acromiale in these cases.

PMID- 9040141
TI  - Imaging of primary multifocal osseous lymphoma.
AB  - OBJECTIVE: To review our experience with primary multifocal osseous lymphoma
      (PMOL), to characterize its imaging features, before and after treatment, and to
      correlate these features with clinical outcome. DESIGN: Hospital charts and
      imaging studies in eight patients with PMOL were reviewed. These included bone
      radiographs, bone scans, CT and MRI. Number, distribution and appearance of
      lesions before treatment were evaluated; and post-treatment changes were assessed
      for evidence of healing or progression, correlated with clinical outcome.
      RESULTS: A total of 63 lesions were identified by pre-treatment bone scan, 36 by
      MRI (including 10 not visible on bone scan) and 16 by radiographs. Twenty-one
      percent of lesions occurred about the knee, and 63% of patients had concomitant
      skull, distal femoral and proximal tibial lesions. The radiographic appearance
      ranged from lytic to sclerotic. Lesions were isointense to hematopoietic marrow
      on T2-weighted MR sequences. Only plain radiographic evidence of healing or
      progression correlated with clinical outcome. CONCLUSION: Distribution of PMOL
      was best assessed by bone scan. However, MRI revealed larger areas of marrow
      involvement and detected lesions in the pelvis not seen on bone scan. Marrow
      involvement around the knee was common, and the combination of skull, distal
      femoral and proximal tibial lesions may suggest the diagnosis. Radiographs
      underestimate the extent of disease but were the best modality for assessment of
      treatment response.

PMID- 9040142
TI  - Candida osteomyelitis and disc space infection of the lumbar spine.
AB  - Candida osteomyelitis is an uncommon complication of immunosuppressive therapy.
      Its radiographic manifestations are similar to those of other relatively indolent
      infectious agents. We report the CT and MR findings in a patient who developed
      this condition following treatment for acute myelogenous leukemia, and review the
      imaging literature covering similar cases.

PMID- 9040143
TI  - Primary hemangiopericytoma of bone located in the tibia.
AB  - Primary hemangiopericytoma of the bone is a rare tumor. We describe a patient
      with primary hemangiopericytoma of the tibia treated by surgery. The clinical and
      radiological features of this tumor are described. The radiological and
      histopathological different diagnosis of hemangiopericytoma is discussed.

PMID- 9040144
TI  - Epiphyseal extension of a unicameral bone cyst.
AB  - Epiphyseal extension of a unicameral bone cyst is rare. We report a case of a 13
      year-old boy with three pathological fractures through a unicameral bone cyst
      with epiphyseal involvement in the proximal humerus. These lesions initially
      tends to expand the humeral epiphysis laterally and progress medially. They also
      commonly cause a slip of the epiphysis in a medical direction. They also have a
      greater association with growth retardation and lesser degree of recurrence than
      their metaphyseal counterpart.

PMID- 9040145
TI  - Gorham syndrome of the thorax and cervical spine: CT and MRI findings.
AB  - Gorham syndrome is a rare disorder that is characterized by local osseous
      invasion and surrounding soft tissues by an angiomatous mass, eventually causing
      lysis of the affected bone. To date, only four cases have reported the MR imaging
      appearance of this disease and the findings have been variable. We present a case
      involving the cervical and thoracic spine and part of the osseous hemithorax with
      attention to the MR findings.

PMID- 9040146
TI  - Intraosseous neurilemmoma of the fibula.
AB  - We present a case of intraosseous neurilemmoma of the fibula in a 56-year-old
      woman. The case showed the typical radiographic appearance except for the
      presence of spotted calcifications that mimicked a cartilaginous tumor. Enhanced
      MR images revealed the heterogeneity of the tumor, which consisted of Antoni type
      A and B tissue.

PMID- 9040147
TI  - Malignant hemangioendothelioma of the left calcaneus associated with fever and
      hematological abnormalities.
AB  - A case of malignant hemangioendothelioma of the left calcaneus associated with
      unique system manifestations is reported here. The severe toxic manifestations
      included: high fever, anemia, leukocytosis, coagulation abnormalities, and other
      signs. Because of poor response to many antibiotic regimens, the confusion of
      diagnosis, and severe coagulation abnormalities with clinical signs that the life
      of the patient was endangered, below the knee amputation was performed.
      Pathological studies revealed a malignant hemangioendothelioma. A review of the
      case suggests that the signs and symptoms were possibly due to an immune response
      to the tumor rather than to secondary infection, although the latter possibility
      cannot be completely excluded.

PMID- 9040148
TI  - Intraosseous ganglion in a 6-year-old boy.
AB  - The case of a 6-year-old child with an intraosseous ganglion of the distal femur
      is reported. We believe this is the youngest patient reported with this
      condition.

PMID- 9040149
TI  - Magnetic resonance imaging features of chloroma of the shoulder.
AB  - A patient with a history of essential thrombocytosis presented with diffuse
      skeletal pain and restricted motion of the left shoulder. Magnetic resonance
      imaging (MRI) of the left glenohumeral joint showed a soft tissue mass that
      displaced the rotator cuff. Biopsy of the mass revealed chloroma. MRI is the
      method that best characterizes this lesion.

PMID- 9040155
TI  - Resection for cure of adenocarcinoma of the head of the pancreas: the greater
      Hartford experience.
AB  - BACKGROUND: Nationally, the results of pancreaticoduodenectomy for adenocarcinoma
      of the pancreas have improved. Therefore, we examined our experience with this
      operation. METHODS: A retrospective review of tumor registry data from four
      greater Hartford, Connecticut, hospitals identified 51 patients who underwent
      pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas between
      1982 and 1992. RESULTS: The 30-day operative mortality rate for the group was 4%.
      Life table survival analysis revealed a five-year survival rate of 15% and a
      median survival of 15 months. Twelve patients had postoperative radiation therapy
      and chemotherapy. The median survival in this group was 36 months, significantly
      longer than that of the nonadjuvant therapy group (13 months, P < .02). No
      difference in operative mortality or ultimate survival was seen between the
      hospital with the largest experience and the three other hospitals. CONCLUSIONS:
      Pancreaticoduodenectomy can be performed safely at hospitals with relatively low
      pancreaticoduodenectomy volume. Survival rates are longer than in past reviews.

PMID- 9040156
TI  - Total clinical laboratory test volume in Connecticut, 1994-1995.
AB  - OBJECTIVE: To measure the volume of clinical laboratory testing in Connecticut
      during a one-year period. To explore the potential value of such data. DESIGN:
      Summary and analysis of federal and state clinical laboratory
      registration/licensure/inspection forms. SETTING: 2,333 clinical laboratory test
      facilities registered in Connecticut. MAIN OUTCOME MEASURES: The total clinical
      laboratory output for Connecticut by type of facility and category of technology
      over a 12-month period. RESULTS: During 1995, 2,333 registered clinical
      laboratory test facilities performed approximately 65,427,103 analyses in
      Connecticut. This represents approximately 20 tests per person per year. Thirty
      five acute care hospitals performed 59.4%, nine large commercial laboratories
      33.2%, 30 small commercial laboratories 1.7%, 1,491 physicians' offices 3.9%, and
      a miscellaneous group 1% of the tests. Test volumes are further segregated into
      eight major categories of technology: chemistry 59%, hematology 23.3%,
      microbiology 5.6%, blood banking 2.9%, coagulation 2.8%, waived tests 2.7%, urine
      analysis 1.8%, cytology 0.9%, and histology 0.8%. CONCLUSION: For the first time
      mechanisms are in place to measure essentially all clinical testing for a given
      area. With minor changes the data collection system could be greatly improved.
      The possible uses for such a data bank are discussed.

PMID- 9040157
TI  - Reducing the inappropriate utilization of clinical laboratory tests.
AB  - Reimbursement policies for health-care services in Connecticut and the U.S. have
      gradually shifted towards fixed reimbursements through implementation of managed
      care. As a result, there is an increasing need by physicians and other care
      givers to reduce costs without compromising the quality of the care being
      delivered. The clinical laboratory is one area where significant cost reductions
      may be realized. More effective utilization can be accomplished with the
      elimination of panels of tests, such as the general chemistry profile, removal of
      antiquated tests or those that provide redundant information, judicious use of
      drug assays, acceptance of clinical practice guidelines, and use of reflex
      testing algorithms. Physicians should also focus more on prognostic indicators
      for disease prevention. Point-of-care testing devices which have higher costs
      than incremental central laboratory expenses should be used only if it reduces
      overall operating expenses, as assessed by outcomes analyses. New technologies
      such as DNA probes can substantially improve diagnostic efficiency. Physicians
      and clinical laboratories must collaborate to achieve more efficient utilization
      practices.

PMID- 9040158
TI  - A case report: recurrent vestibular schwannoma.

PMID- 9040159
TI  - Methadone vs naltrexone.

PMID- 9040160
TI  - Response to Dr. Massey's "Neurasthenia, psychasthenia, CFS, and related matters".

PMID- 9040161
TI  - APhA on the Internet: a user's guide.

PMID- 9040162
TI  - Changes: here and everywhere.

PMID- 9040164
TI  - The total product concept.

PMID- 9040163
TI  - Communication: a way to improve continuity of care?

PMID- 9040165
TI  - Novel therapies for treatment of rheumatoid arthritis.

PMID- 9040166
TI  - Selected pediatric emergencies in community practice.
AB  - In children, the signs and symptoms of serious infection often mimic those
      observed with minor, self-limiting diseases. One of the most important steps in
      making a diagnosis of an infection of the central nervous system is to suspect
      that an infection may be present. Acute epiglotitis predominantly affects
      children 2 to 7 years of age; delays in its diagnosis or treatment may result in
      death within a matter of hours. Pharmacists should be aware of the signs and
      symptoms of child abuse and neglect and understand the reporting procedures and
      requirements.

PMID- 9040167
TI  - Drug therapy for obesity: an update.
AB  - As a method of losing weight and maintaining weight loss, calorie-restricted
      diets are proving ineffective and counterproductive. The best candidates for drug
      therapy for obesity include patients with comorbidities that can be decreased
      with weight loss and those at risk for obesity-related comorbidities. The central
      nervous system properties of the amphetamines have led to chemical alterations of
      the original molecule in the hope of creating an appetite-suppressant drug
      without the potential for abuse. Studies demonstrate that serotonergic drugs can
      induce weight loss in the short term. Patients using nonprescription drugs for
      weight loss that have not been approved for that purpose should be informed that
      efficacy is unproved and warned that, in some cases, adverse effects could be
      serious.

PMID- 9040168
TI  - Status of research on gender differences.
AB  - Gender bias persists in the use of women in clinical trials, but the situation is
      improving. Pharmacokinetics is an obvious area in which to examine gender
      differences in the absorption, distribution, metabolism, and elimination of
      drugs. Pharmacokinetics change during pregnancy and during the different phases
      of woman's life cycle. The federal government has undertaken a long-range study
      of the diseases, disorders, and conditions of women: the Women's Health
      Initiative.

PMID- 9040170
TI  - Population pharmacokinetics/pharmacodynamics and individualized drug therapy.
AB  - Drug concentration and effect vary among patients for any given dose. A goal of
      population pharmacokinetics (PK) and pharmacodynamics (PD) is to identify patient
      specific factors such as weight, creatinine clearance, and age, and associate
      them with the observed PK/PD differences. Once associated with differences in
      concentration or response, these distinguishing factors may then be used to
      better individualize drug therapy. Studies of the population PK of teicoplanin
      and the population PK and PD of felodipine are summarized as examples of this
      approach.

PMID- 9040171
TI  - Pharmaceutical care for rural patients: ominous trends.
AB  - The findings of the Lake Superior Rural Cancer Care Project may be a harbinger of
      impeding shortages of pharmacists in most rural areas of the United States.
      Elderly patients, the population that is most reliant on medication, constitute a
      large portion of the citizens who are potentially underserved in terms of
      pharmaceutical care in rural areas. Education for rural practice is largely
      overlooked in current pharmacy curricula. The national pharmacy leadership must
      develop a sensible workforce policy that considers the needs of rural patients.

PMID- 9040172
TI  - HIV-positive males' satisfaction with pharmacy services.
AB  - The objective of this study was to describe the pharmacy needs of a group of
      males infected with human immunodeficiency virus (HIV) and to determine whether
      those needs were being met. An anonymous survey was used to determine the
      perceptions of a group of HIV-positive males. Of 62 usable responses, 53.2% of
      respondents tested positive for HIV more than five years ago and 58.1% reported a
      CD4 count below 200/mm3, the mean age was 41 years (SD = 8.6). Respondents
      indicated a need for a pharmacist knowledgeable in HIV disease/treatment (74.5%),
      a pharmacy that accepts all insurance (66.6%), and information on alternative
      therapies (29.4%). Most (72.6%) wanted both written and oral information, and
      more than half expected the pharmacist to provide information on side effects,
      how medications interact with other medications and with food and how to take the
      medication. More than 85% indicated satisfaction with pharmacy services. The
      study concluded that HIV-positive males have certain expectations for pharmacy
      services, such as the provision of written and oral information, specific
      medication information, and personal interaction with the pharmacist. These
      patients are satisfied to varying degrees with different aspects of
      pharmaceutical care Pharmacists should provide these expected services to
      increase satisfaction for all patients, especially those who are HIV positive.

PMID- 9040173
TI  - Response forms reflect pharmacists' participation in retrospective DUR.
AB  - This study examined pharmacists' responses to two different Medicaid
      retrospective therapeutic interventions (excessive use of beta 2-agonist inhalers
      and long-term use of sedatives) in New Mexico. It also examined the types of
      actions pharmacists reported taking, and the differences between actions taken by
      physicians and pharmacists in terms of response rate, tone of responses, and time
      spent responding to the intervention. The most frequent pharmacist action was to
      call the physician. Response rates for the drug use review (DUR) program were
      higher for physicians than for pharmacists; pharmacists also took twice as long
      as physicians to respond to both interventions. The study results indicate a need
      for better methods to document clinical services performed by pharmacists under
      the Medicaid DUR program to obtain reimbursement and justify therapeutic
      decisions. Pharmacists also need documentation methods that are relatively easy
      to use so that they can respond more quickly to interventions.

PMID- 9040176
TI  - What makes patients think that their pharmacists' services are of value?

PMID- 9040177
TI  - Diagnostic imaging: an overview for the pharmacist.

PMID- 9040178
TI  - Women's health education: an opportunity for community pharmacy.

PMID- 9040179
TI  - Our fate lies in our genes.

PMID- 9040180
TI  - Interview with Joseph W. Sokolowski, Jr, MD. Interview by Bill Berlin.

PMID- 9040181
TI  - MSNJ's been workin' on the web.

PMID- 9040182
TI  - Do we know the answers to genetic testing?
AB  - Advances in prenatal screening, the development of new direct DNA tests for once
      rare familial diseases, and society's improved understanding and acceptance of
      genetic screening prior to conception, will keep genetic counselors busier than
      ever in the 21st century. As more and more direct DNA tests become available
      through the work of the Human Genome Project, genetic counselors like UMDNJ's
      Lorraine Suslak will become even more valuable to time-pressed physicians.
      Indeed, advances are made so fast in this area, that when patients come to Alan
      E. Donnenfeld, MD, for prenatal diagnosis, he often contacts Helix, a national
      organization that keeps a database of the latest tests available.

PMID- 9040183
TI  - Early stage vocal cord cancer: results after external beam radiotherapy.

PMID- 9040184
TI  - Futile medical therapy: a model policy.

PMID- 9040185
TI  - Adults with cerebral palsy.

PMID- 9040186
TI  - What do New Jerseyans want from physicians?

PMID- 9040187
TI  - Health care law: a growing frontier.

PMID- 9040188
TI  - Should minors be held accountable for tobacco use?

PMID- 9040189
TI  - Barrett's esophagus: does the incidence of adenocarcinoma matter?

PMID- 9040190
TI  - Liver toxicity does not have to follow methotrexate therapy of patients with
      rheumatoid arthritis.

PMID- 9040191
TI  - Aequanimitas, ... and then some.

PMID- 9040192
TI  - Ulcerative colitis practice guidelines in adults. American College of
      Gastroenterology, Practice Parameters Committee.
AB  - Guidelines for clinical practice are intended to indicate preferred approaches to
      medical problems as established by scientifically valid research. Double-blind
      placebo controlled studies are preferable, but compassionate use reports and
      expert review articles are utilized in a through review of the literature
      conducted through Medline with the National Library of Medicine. When only data
      that will not withstand objective scrutiny are available, a recommendation is
      identified as a consensus of experts. Guidelines are applicable to all physicians
      who address the subject without regard to specialty training or interests and are
      intended to indicate the preferable but not necessarily the only acceptable
      approach to a specific problem. Guidelines are intended to be flexible and must
      be distinguished from standard of care, which are inflexible and rarely violated.
      Given the wide range of specifies in any health care problem, the physician must
      always choose the course best suited to the individual patient and the variables
      in existence at the moment of decision. Guidelines are developed under the
      auspices of the American College of Gastroenterology and its Practice Parameters
      Committee and approved by the Board of Trustees. Each has been intensely reviewed
      and revised by the Committee, other experts in the field, physicians who will use
      them, and specialists in the science of decision of analysis. The recommendations
      of each guideline are therefore considered valid at the time of their production
      based on the data available. New developments in medical research and practice
      pertinent to each guideline will be reviewed at a time established and indicated
      at publication to assure continued validity.

PMID- 9040193
TI  - The incidence of adenocarcinoma in Barrett's esophagus: a prospective study of
      170 patients followed 4.8 years.
AB  - OBJECTIVES: Barrett's esophagus is a premalignant condition defined by the
      presence of intestinal metaplasia in the esophagus. Estimates of the incidence of
      adenocarcinoma developing in patients with Barrett's esophagus vary widely. We
      prospectively followed a cohort of patients to define the incidence. METHODS:
      Between January 1982 and April 1995, all patients undergoing upper endoscopy at
      the VA Medical Center in Tucson, AZ, were surveyed for Barrett's esophagus. One
      hundred seventy-seven patients (174 males, three females) were found to have
      Barrett's esophagus. Seven of 177 were found to have adenocarcinoma either at
      initial endoscopy or within 6 months, resulting in a prevalence of 4%. One
      hundred seventy of 177 patients initially lacking cancer were available for
      systematic survey. RESULTS: The mean age at the time of Barrett's diagnosis was
      62 yr (range 30-85 yr). The mean follow-up period was 57 months or 4.8 yr (range
      6-156 months), for a total of 834 patient-years. Adenocarcinoma developed in four
      patients, an incidence of 1/208 patient-years of follow-up. CONCLUSIONS: The
      current series is larger and has a longer follow-up period than previous
      prospective trials and demonstrates a lower incidence of adenocarcinoma.
      Surveillance of patients with Barrett's esophagus for dysplasia remains an
      appropriate clinical practice.

PMID- 9040194
TI  - The lack of association between adenocarcinoma of the esophagus and gastric
      surgery: a retrospective study.
AB  - BACKGROUND: The cause of the rapid increase in the incidence of adenocarcinoma of
      the esophagus since the 1970s is unknown. OBJECTIVE: To test the hypothesis that
      duodenogastroesophageal reflux causes adenocarcinoma of the esophagus by
      comparing the frequency of gastric surgery (a human model of
      duodenogastroesophageal reflux) and other potential risk factors between patients
      with adenocarcinoma and patients with squamous cell carcinoma of the esophagus.
      METHODS: Medical records of all patients with adenocarcinoma or squamous cell
      carcinoma of the esophagus seen at the Cleveland Clinic Foundation between 1987
      and 1994 were reviewed. The following data were retrieved: age, gender, race,
      tumor location, history of gastric surgery and gastroesophageal reflux symptoms,
      and use of tobacco, alcohol, histamine-2 receptor antagonists, and proton pump
      inhibitors. RESULTS: The data of 325 patients with adenocarcinoma (73.5%) and 117
      patients with squamous cell carcinoma (26.5%) were analyzed. No differences were
      found between the groups in age, proportion with gastric surgery (patients with
      adenocarcinoma: 1.2%, 95% confidence interval 0.3-3.1%; patients with squamous
      cell carcinoma: 0.9%, 95% confidence interval 0.0-4.7%), smoking (76.7 vs 81.6%),
      or alcohol use (71.8 vs 79.1%). Significant risk factors associated with
      adenocarcinoma of the esophagus were male gender, white race, distal cancer
      location, and Barrett's esophagus. CONCLUSIONS: Previous gastric surgery is
      rarely found in patients with esophageal cancer and is performed with equal
      frequency in patients with adenocarcinoma and those with squamous cell carcinoma
      of the esophagus. This suggests that gastric surgery and its associated
      duodenogastroesophageal reflux do not play a role in the etiology and rising
      incidence of adenocarcinoma of the esophagus. White males in their mid-60s with
      Barrett's esophagus who smoke and drink alcohol are at highest risk for
      adenocarcinoma of the esophagus.

PMID- 9040195
TI  - Preoperative endoscopic grading of esophagitis versus outcome after laparoscopic
      Nissen fundoplication.
AB  - OBJECTIVES: Preoperative grading of esophagitis has recently been advocated as a
      means of selecting patients suitable either for laparoscopic Nissen
      fundoplication for patients with uncomplicated esophagitis, or for open
      operations in patients with complicated esophagitis (stricture or Barrett's
      esophagus). This study was performed to determine whether the degree of
      esophagitis preoperatively influences the clinical outcome after laparoscopic
      Nissen fundoplication. METHODS: Two hundred thirty-one patients who underwent a
      laparoscopic Nissen fundoplication were classified into three groups according
      esophagitis grade. Of these patients, 59 had no evidence of endoscopic
      esophagitis (group 1), 148 had uncomplicated esophagitis (group 2), and 24 had
      Barrett's esophagus or an esophageal stricture (group 3). Postoperative clinical
      assessment of heartburn, dysphagia, and patient satisfaction using visual
      analogue scales was performed by an independent investigator. RESULTS: No
      significant differences were found between the groups in regard to their clinical
      outcome. CONCLUSIONS: We conclude that laparoscopic Nissen fundoplication is a
      suitable approach for all patients with objectively proven gastroesophageal
      reflux disease selected for surgery, irrespective of their preoperative
      esophagitis grade.

PMID- 9040196
TI  - The effect of cisapride in patients with reflux esophagitis: an ambulatory
      esophageal manometry/pH-metry study.
AB  - OBJECTIVES: The mechanisms responsible for the efficacy of cisapride in
      gastroesophageal reflux disease remain unclear. The current study was designed to
      test the hypothesis that cisapride decreases esophageal acid exposure by
      augmenting esophageal motility and improving acid clearance. METHODS: Eighteen
      patients with reflux esophagitis underwent combined 24-h ambulatory esophageal
      manometry/pH-metry at baseline and then again after 2 wk of cisapride therapy (10
      mg q.i.d.). RESULTS: Esophageal acid exposure was significantly decreased during
      cisapride therapy (total percentage of time pH was < 4: 8.3 +/- 2.0% at baseline
      vs 3.8 +/- 0.6% on cisapride). This was not associated with significant changes
      in contraction amplitude or duration, peristaltic velocity, or the proportion of
      peristaltic contractions. The number of reflux episodes per hour was unchanged by
      cisapride therapy; however, cisapride significantly decreased the number of
      prolonged duration reflux episodes as well as the duration of the longest reflux
      episode. Although the relative proportion of peristaltic versus nonperistaltic
      contractions occurring during reflux episodes was unchanged by cisapride therapy,
      there was a significant increase in the mean number of contractions per minute
      (both peristaltic and nonperistaltic combined) occurring during reflux episodes.
      CONCLUSIONS: These data suggest that cisapride decreases esophageal acid exposure
      by improving esophageal clearance and that this occurs because of an increase in
      the number of esophageal contractions rather than by augmenting contraction
      amplitude or duration or the proportion of peristaltic sequences.

PMID- 9040197
TI  - A prospective characterization of upper gastrointestinal hemorrhage presenting
      with hematochezia.
AB  - BACKGROUND: Although hematochezia is well recognized to occur in patients with
      upper GI hemorrhage (UGIH), its prevalence, clinical presentation, causes, and
      outcome in these patients are not well defined. METHODS: Consecutive patients
      evaluated for UGIH by the gastroenterology service at a large inner city hospital
      from August 1, 1990, through September 31, 1994, were prospectively identified.
      Vital signs and stool color were recorded on admission to the emergency
      department. Endoscopy was performed in all patients, usually within 48 h of
      admission. The cause of bleeding was determined by endoscopy, surgery, or
      autopsy. RESULTS: Over the 50-month study period, 727 patients with UGIH meeting
      the inclusion criteria were evaluated, with 104 (14%) presenting with
      hematochezia (18 with bright red blood and 86 with maroon blood). The most common
      causes of bleeding were duodenal ulcer (44%) and gastric ulcer (20%). In
      comparison with patients with melena (N = 441), patients with hematochezia were
      older (55 vs 50 yr, p < 0.01) and more likely to present with duodenal ulcer
      bleeding (43 vs 25%, p < 0.01); no differences in vital signs, including
      prevalence of shock, or admission Hb concentration were found. However,
      transfusion requirements (5.4 vs 4.0 units, p = 0.01), need for surgery (11.7 vs
      5.7%, p = 0.03), and mortality (13.6 vs 7.5%, p = 0.05) were significantly higher
      in patients with hematochezia than in those with melena, suggesting more severe
      bleeding and a worse outcome. CONCLUSIONS: Hematochezia is common in patients
      with UGIH, and the presenting features are similar to those of patients with
      melena. Duodenal ulcer is the most common cause of bleeding associated with
      hematochezia. Patients with UGIH and hematochezia seem to have a worse prognosis.

PMID- 9040198
TI  - Acute upper gastrointestinal bleeding in the Amsterdam area: incidence,
      diagnosis, and clinical outcome.
AB  - OBJECTIVES: In the United States of America and the United Kingdom several
      epidemiological upper gastrointestinal bleeding (UGIB) surveys have been done.
      However, information about the current epidemiology of acute UGIB in continental
      Western Europe is sparse. METHODS: From July of 1993 to July of 1994, 951
      patients with acute UGIB were prospectively included in 12 hospitals in the
      Amsterdam area. Data were collected prospectively with a standard questionnaire
      and included demographic as well as specific data relating to UGIB. RESULTS: The
      overall incidence was 45 per 100,000 persons/yr. Patients had an advanced age
      (median, 71 yr), and shock was found in 63%. Coexisting illnesses were present in
      85%. Twenty percent had a history of previous ulcer disease, of whom 33% used
      acid suppressive therapy. Endoscopy was performed within 24 h in 78%, and in 42%
      a gastroduodenal ulcer was found. In 24%, no diagnosis could be made at the
      initial endoscopy, in these patients endoscopy was done significantly later than
      in those in whom a diagnosis was readily made. Rebleeding occurred in 16.4%, and
      7% had surgery. Mortality rate was 13.9%, which was considered in one-third to be
      directly related to the bleeding. CONCLUSIONS: The incidence and diagnostic
      profile of UGIB is similar to other large European studies, but different from
      those for the United States. Bleeding could perhaps have been prevented in the
      patients with a history of previous ulcer disease. The 24-h endoscopy service was
      not as fast, accurate, and widespread as we assumed. Mortality seems to be more
      related to advanced age, shock, and coexisting illnesses.

PMID- 9040199
TI  - Effective 2-wk therapy for Helicobacter pylori disease in children.
AB  - Successful eradication of Helicobacter pylori infection in children has required
      long treatment regimens that may result in noncompliance with failure to
      eradicate this organism. Despite full compliance with shorter therapeutic
      regimens, such as amoxycillin and omeprazole for 2 wk, the H. pylori eradication
      rate is poor in children. OBJECTIVES: The aim of this study was to evaluate the
      efficacy of, and compliance with, a 2-wk treatment with metronidazole,
      omeprazole, and clarithromycin in eradicating H. pylori disease in children.
      METHODS: Over a 15-month period, children diagnosed to be H. pylori positive by
      Steiner's stain of gastric antral biopsy specimens were treated with
      metronidazole, omeprazole, and clarithromycin. Follow-up upper GI endoscopy was
      performed 6-8 wk after completion of therapy. RESULTS: Of 15 patients with H.
      pylori-positive antral gastritis, 11 had duodenal ulcer disease; three patients
      with severe abdominal pain and one with vomiting had H. pylori gastritis only. H.
      pylori eradication was seen in 11 of 11 (100%) patients with duodenal ulcer
      disease and in three of four (75%) with gastritis only; the overall success rate
      was 93%. Duodenal ulcer disease healed when H. pylori was eradicated in all but
      one patient, who at presentation had a penetrating ulcer with a duodenobiliary
      fistula. Fourteen of 15 patients (93%) were fully compliant, and no adverse
      reactions were reported. CONCLUSIONS: Two weeks of therapy with metronidazole,
      omeprazole, and clarithromycin is effective H. pylori therapy in children. It is
      well tolerated, and full compliance can be achieved.

PMID- 9040200
TI  - Highly effective twice-daily triple therapies for Helicobacter pylori infection
      and peptic ulcer disease: does in vitro metronidazole resistance have any
      clinical relevance?
AB  - OBJECTIVES: To compare cure rates of Helicobacter pylori (H. pylori) infection,
      ulcer healing, and side effects of three simplified regimens of triple therapy in
      patients with peptic ulcer disease. METHODS: Two hundred thirty-one patients were
      prospectively randomized to receive either regimen OAM (omeprazole 20 mg b.i.d.,
      amoxicillin 750 mg b.i.d., and metronidazole 400 g b.i.d.), OCM (omeprazole 20 mg
      b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d.), or BCM
      (bismuth subcitrate 240 mg b.i.d., clarithromycin 250 mg b.i.d., and
      metronidazole 400 mg b.i.d.), all for 10 days. Side effects were reported
      immediately afterward in a self-administered questionnaire. Upper endoscopy was
      carried out before treatment and 2 months after treatment. Three antral and three
      corpus biopsy specimens were analyzed microbiologically and with rapid urease
      test to determine the presence of H. pylori. Altogether 143 patients (62%) had an
      active ulcer at start of treatment. Metronidazole resistant (M-R) H. pylori
      strains were found in 30% of patients, while none had clarithromycin resistant (C
      R) strains. RESULTS: According to intention-to-treat analysis, H. pylori cure
      rates were 91, 95, and 95% with OAM, OCM, and BCM, respectively (p = 0.63). In
      patients with metronidazole-sensitive (M-S) strains versus M-R strains, the cure
      rates were 96 versus 77% with OAM (p = 0.025), 94 versus 94% with OCM, and 94
      versus 96% with BCM. Ulcer healing rates were 95, 94, and 92%, respectively (p =
      0.91). There were no significant differences in side effects between the
      regimens, and only five patients (2%) had to stop the treatment prematurely.
      CONCLUSIONS: All treatment regimens were highly effective for cure of H. pylori
      infection and for ulcer healing. Metronidazole resistance reduced the efficacy of
      OAM, but was of no importance for the efficacy of OCM or BCM. Side effects were
      of minor importance.

PMID- 9040201
TI  - The Pyloritek test and the CLO test: accuracy and incremental cost analysis.
AB  - OBJECTIVE: The aim of this study was to compare the Pyloritek test (a 1-h rapid
      urease test) to the widely used CLO test. METHODS: Seventy-one patients
      undergoing upper endoscopy were studied. All patients gave informed consent. A
      single antral biopsy specimen was obtained for the CLO test, and another was
      obtained for the Pyloritek test. Additional specimens were obtained for culture
      and processed in the event of a discordant result. The Pyloritek assay was read
      at 1 h by one observer. The CLO test was read at 24 h by an observer blinded to
      the results of the Pyloritek assay. RESULTS: There were 18 males and 53 females,
      and the mean age (+/- SEM) was 53 +/- 17 yr. Thirty-two patients had a positive
      result on the CLO test, and 39 had a negative test result. Of the 32 patients
      with a positive CLO test result at 24 h, 31 were positive by the Pyloritek test
      at 1 h. All 39 patients with negative CLO test results had negative Pyloritek
      test results as well. There was one discordant result, a negative Pyloritek test
      result and a positive CLO test result. Culture demonstrated growth of
      Helicobacter pylori. The kappa value, a measure of the reliability of the
      Pyloritek test compared with the CLO test, was 0.972 (SE, 0.0284; 95% confidence
      interval, 0.925-1). Marginal cost-effectiveness analysis favored the Pyloritek
      test. CONCLUSIONS: Results of the Pyloritek test at 1 h and the CLO test at 24 h
      are comparable in terms of detection of urease activity.

PMID- 9040202
TI  - Risk of infection with Helicobacter pylori and hepatitis A virus in different
      groups of hospital workers.
AB  - OBJECTIVES: The purpose of this study was to determine whether different staff
      groups in an acute care hospital are at increased risk of acquiring Helicobacter
      pylori and hepatitis A virus infection. METHODS: We examined staff members of an
      acute care hospital for serum antibodies to H. pylori IgG (n = 457) and to
      hepatitis A virus (n = 434). The staff members were assigned to three groups: 1)
      nonmedical staff (n = 110), 2) medical and nursing staff (n = 272), and 3)
      medical and nursing staff working in a gastroenterology and endoscopy unit (n =
      75). Serum antibodies were measured by validated enzyme immunoassays. A
      questionnaire inquiring about medical and professional history, history of upper
      GI pain and ulcer, as well as about the use of nonsteroidal anti-inflammatory
      drugs or medication for GI complaints and smoking habits was completed by each
      person. RESULTS: The seroprevalence of H. pylori was 35.5% in group I, 34.6% in
      group II, and 24.0% in group III (not significant). The seroprevalence of H.
      pylori antibodies increased with age (p < 0.001), and antibodies were present
      more frequently in women than in men (36.2 vs 25.4%, p < 0.05). After adjustment
      for age, duration of experience and the number of years working in the
      gastroenterology or endoscopy unit did not increase H. pylori seropositivity. No
      significant association was found between H. pylori seropositivity and history of
      upper GI pain, ulcers, use of nonsteroidal anti-inflammatory drugs or medication
      for GI complaints, or tobacco use. The prevalence of hepatitis A antibodies was
      similar in the three groups (group I, 26.4%; II, 26.5% III, 21.7%; not
      significant). Cross-tabulation showed that 67 subjects (15.4%) were seropositive
      for both H. pylori and hepatitis A (p < 0.001) and that 245 (56.5%) were negative
      for both. Seventy-seven (17.7.%) and 45 (10.4%) were seropositive for only H.
      pylori and for only hepatitis A, respectively. CONCLUSION: Occupational exposure
      to patients in an acute care hospital as well as to patients and to endoscopic
      procedures of a gastroenterology and endoscopy unit does not increase the rate of
      infection with H. pylori. The significant correlation between the seroprevalences
      of H. pylori and hepatitis A antibodies suggests fecal-oral transmission of H.
      pylori.

PMID- 9040203
TI  - Regional differences in gastric acidity and antacid distribution: is a single pH
      electrode sufficient?
AB  - Accurate measurement of intragastric acidity has both clinical and
      investigational importance in studying gastric pathophysiology. OBJECTIVES: The
      aims of this study were fourfold: (1) to investigate whether regional differences
      in intragastric acidity exist; (2) to determine intragastric acidity after a
      standard antacid was administered in both the fasting and fed states; (3) to
      monitor gastric emptying of and anatomic distribution of radiolabeled antacid
      during fasting and postprandial periods; and (4) to determine whether the
      regional effects of ingested antacid correlated with the anatomic distribution of
      the antacid. METHODS: Eight normal male volunteers were studied after
      fluoroscopically guided nasogastric placement of a tube assembly containing four
      pH electrodes, with one electrode in each quartile of the stomach. Simultaneous
      pH readings were made from the four electrodes while fasting, after
      administration of fasting antacid (30 ml, 79 mEq buffering capacity),
      postprandially, and after postprandial antacid ingestion. All subjects repeated
      the protocol on a separate day, five of them using radiolabeled antacid. Gastric
      emptying and gastric distribution over time of radiolabeled antacid were
      determined for comparison to regional intragastric acidity. RESULTS: Intragastric
      acidity varied regionally over time in response to meals and to fasting and
      postprandial antacid. In the fasting state, intragastric acidity returned to
      baseline after antacid ingestion in a proximal to distal (cardia to antrum)
      sequence, while postprandial antacid resulted in a return to baseline acidity in
      a distal to proximal (antrum to cardia) sequence. Radiolabeled antacid
      distribution paralleled intragastric pH and hydrogen ion concentration in the
      fasting state, with 82% of the antacid localizing in the distal half of the
      stomach within the first minute after antacid ingestion. Postprandially, the
      greatest initial and most prolonged antacid buffering effect occurred proximally,
      correlating with the presence of radiolabeled antacid. Postprandial antacid
      remained in the stomach for a longer time (T1/2 = 93.1 +/- 23.4 min) compared
      with fasting antacid (T1/2 = 23.6 +/- 11.1 min). CONCLUSIONS: Measurement of
      acidity in the four quartiles of the stomach demonstrated regional variation in
      response to both food and a standard antacid. A single pH electrode does not
      detect regional intragastric pH differences.

PMID- 9040204
TI  - Solitary and multiple pyogenic liver abscesses: characteristics of the patients
      and efficacy of percutaneous drainage.
AB  - OBJECTIVES: Although percutaneous drainage has emerged as one of the first line
      of therapies for pyogenic liver abscesses, the presence of multiple abscesses may
      warrant surgical drainage, which remains controversial in the literature. We
      studied whether the multiplicity of the lesions influences the outcome of the
      treatment. METHODS: Ultrasonography-guided percutaneous drainage was carried out
      in 48 patients with pyogenic liver abscesses. The abscesses were solitary in 38
      patients and multiple (two to seven lesions) in 10 patients. Clinical
      characteristics and the efficacy of the treatment were compared between these two
      groups. RESULTS: Biliary diseases and malignancies were more frequently observed
      in the solitary cases than multiple cases. A past history of surgery for
      cholelithiasis was seen exclusively in the multiple cases. E. coli was more
      frequently cultured from the abscesses in the multiple cases. Three of the
      multiple cases required more than a single catheter. All of the multiple cases
      and 36 of the 38 solitary cases were successfully treated. Two patients died of
      biliary peritonitis as a complication of the procedure, and three died of other
      underlining diseases. CONCLUSION: Ultrasonography-guided percutaneous drainage is
      effective even in patients with multiple pyogenic liver abscesses by adding
      catheters to obtain sufficient drainage.

PMID- 9040205
TI  - Percutaneous drainage of intra-abdominal abscesses in Crohn's disease: short and
      long-term outcome.
AB  - OBJECTIVE: To determine whether percutaneous drainage of Crohn's abscesses
      obviates the need for early surgical drainage. METHODS: All cases of percutaneous
      drainage of Crohn's abscesses between 1990 and 1995 were reviewed and classified
      as a success or failure on the basis of the need for surgery within < 30 days of
      catheter removal. RESULTS: Twenty-seven drainage procedures were performed in 24
      patients; 15 (56%) were classified as successes, and 12 (44%) were classified as
      failures. Successes and failures did not significantly differ with respect to
      patient demographics and Crohn's disease characteristics. Patients whose
      abscesses were successfully drained had significantly fewer associated fistulae
      (46.6 vs 92.0%, p = 0.037), and their abscesses tended more often to be first (vs
      recurrent), spontaneous (vs postoperative), located in the right lower quadrant,
      and smaller. Patients whose abscesses were successfully drained also tended to
      spend more time with the catheter in place and to require more imaging
      procedures. Complications were noted in four cases (15%), enterocutaneous fistula
      at the site of catheter insertion in three cases and postprocedure fever in one
      case. Hospital stay was significantly shorter after successful drainage (16.3 +/-
      6.9 vs 31.7 +/- 22.1 days, p = 0.017). After a total of 543.5 patient-months of
      follow-up, subsequent intra-abdominal Crohn's-related surgery was required in
      only two of the successes and one failure. CONCLUSIONS: 1) Percutaneous drainage
      of Crohn's abscess successfully obviates the need for early surgery in
      approximately 50% of cases, and this benefit is maintained on long term follow
      up. 2) Percutaneous drainage shortens hospital stay. 3) Crohn's abscesses in
      various locations, single or multiple, with or without an associated fistula may
      be successfully drained percutaneously. 4) Presence of an associated fistula may
      be a risk factor for failure.

PMID- 9040206
TI  - A case series of transplant recipients who despite immunosuppression developed
      inflammatory bowel disease.
AB  - OBJECTIVES: We describe 14 patients who developed inflammatory bowel disease
      (IBD) after transplantation despite immunosuppression. METHODS: Using an
      electronic medical archival retrieval system, records of 6800 liver and kidney
      transplant patients were searched for evidence of IBD. The pathology was
      reviewed, and infectious etiologies were excluded. RESULTS: Fourteen patients
      developed IBD after transplantation. Twelve patients had undergone liver
      transplantation, and two kidney transplantation. Four had transplantation for
      autoimmune hepatitis; four for non-A, non-B, non-C hepatitis; two for primary
      sclerosing cholangitis; one for giant cell hepatitis; one for biliary atresia;
      one for polycystic kidney disease; and one for obstructive uropathy. Mean age at
      development of IBD was 38 yr. Mean time to development of IBD after
      transplantation was 4 yr. Endoscopically there were two cases limited to the left
      side, eight of pancolitis, of which one had terminal ileal disease, and four of
      patchy colitis. Histology was consistent with ulcerative colitis in nine patients
      and Crohn's disease in five. Patients with ulcerative colitis either responded
      and remained in remission on maintenance therapy (seven of nine) or were
      refractory and required a colectomy (two of nine). Patients with Crohn's disease
      continued to have flares despite treatment (five of five). CONCLUSION: 1) New
      onset IBD can develop after solid organ transplantation, despite use of
      immunosuppressive therapy. 2) A full spectrum of IBD can be seen after
      transplantation. 3) Study of these patients could shed light on why
      immunosuppression is not uniformly effective for IBD and provide clues to the
      inflammatory determinants of IBD.

PMID- 9040207
TI  - Leukocyte migration in acute colonic inflammatory bowel disease: comparison of
      histological assessment and Tc-99m-HMPAO labeled leukocyte scan.
AB  - Noninvasive leukocyte scintigraphy for assessment of localization, extent, and
      degree of active inflammation in acute colonic inflammatory bowel disease have
      been shown to correlate well with endoscopy. This study compared findings of
      mucosal leukocyte migration assessed histologically with those of technetium 99m
      hexamethylpropylene-amineoxime-labeled leukocyte scintigraphy. PATIENTS AND
      METHODS: Twenty-one patients hospitalized because of a first attack or a relapse
      of known inflammatory bowel disease were investigated using leukocyte
      scintigraphy followed by total colonoscopy with multiple biopsies within 24 h.
      Histological interpretation focused on the degree of segmental mucosal leukocyte
      infiltration. RESULTS: Fourteen patients with ulcerative colitis (UC) and seven
      with colonic Crohn's disease (CD) were included. With the use of histology as the
      reference method, maximal proximal disease extent was correctly assessed by the
      leukocyte scan in 11 patients (8 with UC, 3 with CD), although the rectal
      involvement was not visualized in 5. In seven patients, the extent assessments
      almost matched (+/- one segment), and in the remaining three patients (two UC,
      one CD) the scan grossly misinterpreted active histological inflammation (> or =
      +/- two segments). In patients with UC, the sensitivity, specificity, and
      diagnostic accuracy concerning the extent of inflammation were 0.84, 0.79, and
      0.83, respectively. In patients with CD, the sensitivity was 0.79, and the
      diagnostic accuracy was 0.78. The relative leukocyte scan activity score was less
      concordant with the degree of mucosal leukocyte infiltration but still
      significantly correlated (r = 0.616, p < 0.0001 in UC patients and r = 0.441, p <
      0.003 in CD patients). CONCLUSION: Images created by the technetium 99m
      hexamethylpropylene-amineoxime-labeled leukocyte scan in acute colonic
      inflammatory bowel disease correlate to mucosal leukocyte migration in terms of
      proximal disease extent and, to a lesser degree, also to the intensity of mucosal
      inflammatory infiltration.

PMID- 9040208
TI  - Immunohistochemical localization of group II phospholipase A2 in colonic mucosa
      of patients with inflammatory bowel disease.
AB  - OBJECTIVES AND METHODS: We previously reported the increased contents of group II
      phospholipase A2 (PLA2) in inflamed colonic mucosa of patients with Crohn's
      disease and ulcerative colitis (UC). However, the cellular source of the
      increased group II PLA2 has remained to be clarified. In the present study, we
      examined immunohistochemical localization of group II PLA2 in inflamed colonic
      mucosal biopsy samples obtained from eight patients with Crohn's disease, seven
      with UC, and in normal colonic mucosa of six control subjects without
      inflammatory bowel disease using a monoclonal antibody raised against human group
      II PLA2. RESULTS: and CONCLUSIONS: On immunoblot analysis using the antibody, a
      single band was detected on each lane containing colonic mucosal homogenates from
      a control subject, a Crohn's disease patient, or a UC patient at the same
      position as human group II PLA2 purified from ileal mucosa. The results of
      immunohistochemistry showed that colonic epithelial cells in inflamed mucosa
      obtained from all active Crohn's disease patients examined (n = 4) contained
      immunoreactive group II PLA2. In four of seven patients with active UC, group II
      PLA2 immunoreactivity was similarly positive. No apparent group II PLA2
      immunoreactivity was detected in all colonic mucosal biopsy samples obtained from
      inactive Crohn's disease patients (n = 4) and control subjects. The present study
      supports the presence of group II PLA2 in colonic epithelial cells in actively
      inflamed mucosa of patients with Crohn's disease and UC, which suggests that
      epithelial cells may serve as the cellular source of increased group II PLA2
      content in inflamed colonic mucosa of these patients.

PMID- 9040209
TI  - How reproducible are measures of the anal sphincter muscle diameter by endoanal
      ultrasound?
AB  - Anal endosonography is an imaging technique for the anal sphincter system and
      offers analysis of its muscular integrity. It is generally assumed that
      measurement of the thickness of muscle layers is provided by sonography; however,
      reproducibility of such measurements have not yet been investigated. METHODS:
      Study 1: In 10 healthy volunteers, endoanal ultrasound was performed
      independently by two experienced investigators with two different ultrasound
      machines, and thickness of the muscle layers of the internal and external anal
      sphincter was assessed in the position of the intermediate dorsal anal canal in a
      randomized cross-over fashion. Study 2: In a study of similar design, sonography
      was performed in nine healthy volunteers by two investigators independently using
      a single ultrasound machine in three standardized positions
      (proximal/intermediate/distal anal canal) and the sphincter layers assessed in
      the left, right, and dorsal segment. RESULTS: Study 1: Both the same investigator
      with different ultrasound scanners and different investigators with the same
      machine failed to obtain reproducible results with respect to internal and
      external anal sphincter muscle layer diameter (four bivariate correlations, all
      with p > 0.05). Study 2: Standardization of the probe position did not improve
      the agreement (2 x 9 bivariate correlations, all but two p > 0.05). CONCLUSION:
      At present, therefore, endoanal ultrasound does not provide reliable morphometric
      data on anal sphincter muscle diameter. This could explain previously conflicting
      observations of associations between anal sphincter morphometry and function.

PMID- 9040210
TI  - A pilot study of motility and tone of the left colon in patients with diarrhea
      due to functional disorders and dysautonomia.
AB  - OBJECTIVE: Our aim was to identify qualitative or quantitative colonic motor
      patterns induced postprandially in a pilot study of patients with diarrhea due to
      functional disease or dysautonomia to identify objective endpoints for future
      studies. METHODS: In patients with functional diarrhea (n = 5) or dysautonomia (n
      = 4) in whom GI transit was documented by scintigraphy, we studied colonic
      motility by combined manometry and barostat measurements for 1 h fasting and 2 h
      postprandially (1000-kcal meal). Data were compared with those of healthy control
      subjects. RESULTS: There were no differences in compliance, overall phasic
      motility of the left colon, fasting tone, or maximal change in postprandial tone
      in the diarrhea group as compared with the control group. The diarrhea group
      showed more high amplitude propagated contractions 4.4 +/- 3.6 (SD)/2 h, p <
      0.05) compared with the control group (0.7 +/- 1.4/2 h); the mean postprandial
      tonic response (12 +/- 14%, p < 0.05) and its duration were reduced in the
      diarrhea group compared with the control group (27 +/- 17%). Two dysautonomic
      patients showed a paradoxical relaxation of the colon postprandially. CONCLUSION:
      Reduced duration of increased colonic tone postprandially and increased number of
      high amplitude propagated contractions seem to be useful objective endpoints for
      future studies.

PMID- 9040211
TI  - Tissue factor pathway inhibitor concentrations in cirrhotic patients with and
      without portal vein thrombosis.
AB  - OBJECTIVES: Our aim was to determine whether tissue factor pathway inhibitor
      (TFPI), a physiologically important natural anticoagulant that acts by inhibiting
      the extrinsic pathway, concentrations decrease as liver disease progresses, and,
      second, whether TFPI has an etiologic role in portal vein thrombosis in
      cirrhotics. METHODS: After taking their informed consent, we determined TFPI
      concentrations in the plasma of healthy subjects (group I) (n = 15) (average age,
      45.1 = 11.8 yr), cirrhotics (group II) (n = 16) (average age, 43.6 +/- 9.8 yr),
      and cirrhotics with portal vein thrombosis (group III) (n = 12) (average age,
      42.6 +/- 10.7 yr). Mean and median TFPI values and interquartile ratios were
      determined for groups I, II, and III. Then group II and III were further divided
      according to the Child classes A, B, or C, and mean and median TFPI values and
      interquartile ratios were determined for these classes as well. Using the Man
      Whitney U test, we compared the results. RESULTS: Statistically important
      differences were documented (p = 0.005) between the median TFPI levels of healthy
      adults and Child C cirrhotics (concentration lower in Child C) and between normal
      subjects and cirrhotics with portal vein thrombosis (p = 0.02) (TFPI
      concentration being lower in the latter group again). CONCLUSIONS: TFPI
      concentration decreases in advanced liver disease, and this may be a contributory
      factor for portal vein thrombosis in at least some cases of cirrhotics.

PMID- 9040212
TI  - Polymerase chain reaction-based approaches for detection of allelic loss in the
      p53 tumor suppressor gene in colon neoplasms.
AB  - OBJECTIVES: Inactivation of the p53 tumor suppressor gene is considered to be a
      late event involved in the malignant transformation of colorectal adenoma to
      cancer. Thus, its detection is thought to provide useful information for the
      clinical management of colorectal neoplasms. We devised a rapid screening test
      for allelic loss of the p53 gene by non-radioisotopic single-strand conformation
      polymorphism analysis. METHODS: Biopsy materials from 119 colorectal tumors
      obtained at endoscopy were examined. Three intragenic polymorphic sites were
      amplified by polymerase chain reaction using DNA extracted from these materials,
      and amplified DNA fragments were subjected to non-radioisotopic single-strand
      conformation polymorphism. RESULTS: This method can detect a loss of
      heterozygosity (LOH) of the p53 locus from samples containing over 40% tumor
      derived DNA, and the combination of the three polymorphic markers encompassed
      62.4% of Japanese patients as informative. In adenocarcinoma, an LOH was detected
      in 51.5% (17 of 33) of the samples and in 12.2% (4 of 33) of tubular and/or
      tubulovillous adenomas. The p53 gene was mutated only in samples carrying an LOH,
      that is 64.7% (11 of 17) of carcinomas and 25.0% (1 of 4) of adenomas, but there
      were no mutation in samples retaining both alleles. The presence of an LOH was
      statistically correlated both with p53 mutation and malignant histology (chi 2
      test, p < 0.05). CONCLUSIONS: This method can detect LOH from biopsy material
      obtained at endoscopy. LOH in the p53 locus precedes mutation of the p53 gene,
      and its detection provides useful information of malignancy in colorectal tumors.

PMID- 9040213
TI  - Effect of treatment on bone mass, mineral metabolism, and body composition in
      untreated celiac disease patients.
AB  - BACKGROUND/AIMS: Osteopenia is a common complication of celiac disease. The aims
      of this study were to evaluate whether treatment produces bone remineralization
      and whether calcium and vitamin D supplementation are necessary to reduce
      osteopenia. METHODS: Bone mineral density and biochemical parameters of bone and
      mineral metabolism were measured in 14 newly diagnosed adult celiac disease
      patients. All patients were treated with a gluten-free diet and were randomized
      to receive diet only (n = 7) or diet plus calcium (1.0 g/day) and vitamin D
      (32,000 IU/wk) supplementation (n = 7). Bone density was measured at baseline and
      at 6 and 12 months of follow-up. Tests for biochemical determinations were
      repeated every 3 months. RESULTS: At diagnosis, 11 patients had evidence of
      osteopenia (> 1 SD below normality) in the spine and total skeleton. After 12
      months of gluten restriction, overall bone mass had increased 5.0% (p < 0.01) in
      the lumbar spine and 5.0% (p < 0.002) in the total skeleton. When one only
      considers those 11 patients who strictly followed gluten restriction, bone
      density increased 8.4% in the lumbar spine and 7.7% in the total skeleton.
      Remineralization occurred throughout the skeleton but was more pronounced in the
      axial than in the peripheral skeleton. The increase in bone mass was independent
      of age or menopause. Remineralization in patients treated with diet only was
      similar to that of patients treated with diet and supplements. Basal biochemical
      parameters showed a high bone turnover with secondary hyperparathyroidism.
      Treatment induced a decrease in bone turnover activity. However, a complete
      restoration of biochemical parameters was not achieved. CONCLUSIONS: Strict
      gluten avoidance promoted a significant increase in bone mineral density.
      However, values still remain markedly low after 1 yr in several patients.
      Although calcium and vitamin D supplementation did not provide additional benefit
      to that obtained by diet alone in the doses administered, our results do not
      preclude a possible effect of vitamin D at higher dose.

PMID- 9040214
TI  - Diagnostic features on images in primary small cell carcinoma of the pancreas.
AB  - Small cell carcinoma of the pancreas is a rare tumor with very poor prognosis,
      but the tumor is successfully treated by chemotherapy. Therefore, small cell
      carcinoma must be differentiated from other pancreatic tumors on images. A 71
      year-old man presented with digestive symptoms. Multiple hypoechoic masses were
      detected on transabdominal ultrasonography and lateral shadow and posterior echo
      enhancement on endoscopic ultrasonography. The dynamic computed tomography scan
      revealed that the tumor walls were hypervascular at an early phase, and that the
      central portions were gradually stained at a late phase with differences among
      the tumors; tumor stains were also found on angiography. The distal site of the
      main pancreatic duct was completely interrupted, as seen on endoscopic retrograde
      pancreatography. The resected specimens were composed of circumferential hard
      walls and internally necrotic, hemorrhagic contents of different degrees and were
      microscopically diagnosed as small cell carcinoma. The tumor has to be
      differentiated from hypervascular pancreatic tumors, especially islet cell
      tumors.

PMID- 9040215
TI  - Recurrent small bowel infarction associated with antithrombin deficiency.

PMID- 9040216
TI  - Esophageal carcinoma presenting with nephrotic syndrome: association with anti
      neutrophil cytoplasmic antibody.
AB  - Malignancy is a cause of membranous glomerulonephritis. We report a patient with
      an otherwise asymptomatic squamous cell carcinoma of the esophagus whose
      presenting manifestation was membranous glomerulonephritis and nephrotic
      syndrome. Perinuclear anti-neutrophil cytoplasmic antibody was positive. This is
      the first reported case of perinuclear anti-neutrophil cytoplasmic antibody
      associated with paraneoplastic glomerulonephritis and nephrotic syndrome due to
      esophageal squamous cell carcinoma.

PMID- 9040218
TI  - Deficiency of c-kit+ cells in patients with a myopathic form of chronic
      idiopathic intestinal pseudo-obstruction.
AB  - OBJECTIVES: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a syndrome
      characterized by a failure of intestinal movement, but the cause of dysmotility
      remains unknown. Because interstitial cells of Cajal (ICCs) are believed to
      initiate basic contractile activity of the gastrointestinal tract, there is a
      possibility that changes in ICCs are involved in the development of CIIP. ICCs
      express c-kit in mice, and it has been reported that the c-kit+ cells, the
      location and shape of which resemble those in mice, are detected in the human
      gastrointestinal muscular layer using immunohistochemistry. In the present study,
      we counted the number of c-kit+ cells in the affected intestine of two patients
      with myopathic form of CIIP and compared this number with the number of c-kit+
      cells in the normal intestine. METHODS: The c-kit+ cells in the external muscle
      layer were detected by immunohistochemistry, and the number of them was counted
      under the microscope. Mast cells, which are known to express c-kit, were detected
      by staining with Alcian blue, and the number of them was also counted. RESULTS:
      Immunohistochemistry revealed that the distribution pattern of c-kit+ cells
      resembles that of ICCs in the external muscle layer of normal control subjects.
      The numbers of c-kit+ cells apart from mast cells in two patients with myopathic
      form of CIIP decreased to about 3% of those in normal subjects. CONCLUSIONS: The
      failure of intestinal movement in patients with CIIP, at least in a
      subpopulation, might be related to a deficiency of c-kit+ cells, probably ICCs.

PMID- 9040217
TI  - Meningeal carcinomatosis as the presenting manifestation of gastric
      adenocarcinoma.
AB  - Leptomeningeal involvement is usually reported as a secondary event in advanced,
      already diagnosed, gastric adenocarcinoma. We report a case of leptomeningeal
      carcinomatosis in which identification of mucus-secreting "signet-ring" carcinoma
      cells in the cerebrospinal fluid allowed the diagnosis of an otherwise
      asymptomatic gastric cancer. This is one of the very few reported cases
      manifesting as such in the medical literature.

PMID- 9040219
TI  - AIDS-related non-Hodgkin's lymphoma of the pancreas.
AB  - Non-Hodgkin's lymphoma is a common complication in patients with human
      immunodeficiency virus infection that most frequently affects the
      gastrointestinal tract. We describe the first case report of non-Hodgkin's
      lymphoma primarily involving the pancreas in a 27-yr-old white man who presented
      with epigastric pain, weight loss, and jaundice (and was later found to be HIV
      seropositive). Endoscopic ultrasound and CT scan of the abdomen showed a large
      mass arising from the body and head of the pancreas obstructing the common bile
      duct. An attempted ERCP was unsuccessful due to extrinsic compression and
      distortion of the second part of the duodenum. A percutaneous CT-directed true
      cut needle biopsy of the pancreas revealed a small noncleaved B-cell lymphoma.
      The patient was started on combination chemotherapy. His pancreatic mass,
      epigastric symptoms, and jaundice resolved completely. This case report
      illustrates an otherwise rare presentation of isolated pancreatic involvement of
      non-Hodgkin's lymphoma in a patient with acquired immunodeficiency syndrome. An
      approach to its diagnosis and management is summarized.

PMID- 9040220
TI  - Fatty liver in a case with heterozygous familial hypobetalipoproteinemia.
AB  - We herein present a case of fatty liver in a patient with heterozygous familial
      hypobetalipoproteinemia. A 34-yr-old male presented with abnormally elevated
      levels of transaminases and a fatty liver. He was asymptomatic, and the physical
      examination showed nothing remarkable. The serum total cholesterol, triglyceride,
      LDL-cholesterol, and apolipoprotein B levels all ranged from low normal to one
      half normal. His other laboratory data were all in the normal range. The
      patient's body mass index measured was 25.7 kg/m2, and he did not demonstrate
      obesity. He had no history of alcohol consumption. It was thus thought that the
      fatty liver in this case might be associated with heterozygous
      hypobetalipoproteinemia. Heterozygous hypobetalipoproteinemia with a bright liver
      by ultrasound was also found in several of the patient's family members. Based on
      these rare findings, heterozygous hypobetalipoproteinemia should thus be
      considered as a possible cause in patients presenting with an unexplained fatty
      liver.

PMID- 9040221
TI  - Parathyroid hormone-related protein in an esophageal squamous cell carcinoma with
      tumor-induced hypercalcemia.
AB  - Cancers from patients with tumor-induced hypercalcemia usually produce a
      circulating factor that mimics the parathyroid hormone activity, termed
      parathyroid hormone-related protein. Incidence of tumor-induced hypercalcemia
      appears to be high in patients with squamous cell carcinoma of the esophagus, and
      the presence of parathyroid hormone-related protein have been shown in some
      primary esophageal cancers. In the present study, we have investigated the
      presence of parathyroid hormone-related protein in a patient with metastasized
      squamous cell carcinoma of the esophagus complicated with tumor-induced
      hypercalcemia. Protein was searched by immunohistochemistry, and messenger RNA
      was investigated by reverse transcriptase-polymerase chain reaction and S1
      nuclease assay. Both messenger RNA and protein were detected in hepatic
      metastases, whereas normal esophageal mucosa and primary cancer did not express
      detectable protein or messenger RNA using the S1 nuclease assay. Reverse
      transcriptase-polymerase chain reaction was positive in all these tissues,
      including normal esophageal mucosa. In conclusion, the present case suggests that
      tumor-induced hypercalcemia due to esophageal squamous cell carcinoma may be
      caused by parathyroid hormone-related protein mostly released by liver
      metastases.

PMID- 9040222
TI  - Peritoneal and pleural infection following placement of an internal biliary stent
      for a large bile leak.

PMID- 9040223
TI  - Coumarin-induced hepatic necrosis.

PMID- 9040224
TI  - Transient radiological and colonoscopic features of inflammatory bowel disease in
      a patient with severe Salmonella gastroenteritis.
AB  - Salmonella is the most commonly reported cause of food-borne outbreaks of
      gastroenteritis. We report a case of a severe and toxic form of enteritis caused
      by Salmonella enteritidis. Findings of colonoscopy, an upper G1 tract series, and
      small bowel follow-through were consistent with those of inflammatory bowel
      disease, but the enteritis was self-limited, and the patient recovered after
      supportive treatment only and has remained well.

PMID- 9040225
TI  - Seizure: a rare and transient cause of portal venous gas.
AB  - Gas in the hepatic portal venous system has been noted to be a complication of a
      wide range of intra-abdominal catastrophes that involve damage to bowel mucosa.
      We describe a patient who, after a seizure, was found to have portal venous gas
      on sonography and CT. The search for other possible causes revealed negative
      results. This case demonstrates a rare cause of hepatic portal venous gas that is
      self-resolving and clinically benign.

PMID- 9040226
TI  - Liver penetration by a duodenal ulcer.

PMID- 9040227
TI  - The coexistence of primary esophageal lymphoma and Candida glabrata esophagitis
      presenting as dysphagia and odynophagia in a patient with acquired
      immunodeficiency syndrome.

PMID- 9040228
TI  - Solitary "amyloid ulcer" localized in the sigmoid colon without evidence of
      systemic amyloidosis.
AB  - In a 51-yr-old man, colonoscopy for heme-positive stools revealed a solitary
      "amyloid ulcer" localized in the sigmoid colon. There were no clinical symptoms
      suggesting amyloidosis, and additional examination revealed no findings
      characteristic of amyloidosis or any chronic inflammatory disease. Ischemic
      change as a result of amyloid infiltration into the vessel wall may lead to
      formation of an ulcer in the affected bowel. Although local resection can be
      considered for a symptomatic and well defined lesion, it should be kept in mind
      that amyloid can present in various forms and follow various courses, such as the
      spontaneous healing that occurred in our patient.

PMID- 9040229
TI  - APC gene alterations in Barrett's metaplasia are implicated at an early stage in
      the carcinogenesis of esophageal adenocarcinoma.

PMID- 9040230
TI  - Risk of withdrawing chronic anticoagulation without antithrombotic prophylaxis.

PMID- 9040231
TI  - Gastric outlet obstruction and Helicobacter pylori.

PMID- 9040233
TI  - Prevalence of upper gastrointestinal lesions in patients taking chronic
      nonsteroidal anti-inflammatory drug therapy.

PMID- 9040234
TI  - Difficult liver biopsies: only for radiologists?

PMID- 9040236
TI  - Overlooked variables in students' career choices.

PMID- 9040235
TI  - University of Minnesota--also "bimodal"?

PMID- 9040237
TI  - Medical students and urban violence.

PMID- 9040238
TI  - An elective on violence.

PMID- 9040239
TI  - An innovative AIDS elective.

PMID- 9040240
TI  - Patient variety in residency, and generalist career choice.

PMID- 9040241
TI  - "Managed education": an approach to funding medical education.

PMID- 9040242
TI  - Why do medical students from underrepresented minorities choose--or not choose-
      primary care careers?

PMID- 9040243
TI  - The future of medical schools and teaching hospitals in the era of managed care.
AB  - At the 125 U.S. medical schools and their affiliated teaching hospitals, most of
      the nation's basic and clinical research advances are made, and these translate
      into topflight medical care and great reductions in health care costs (e.g., $30
      billion a year for polio). But these medical schools and teaching hospitals and
      their capacities to provide critical education and research are threatened by
      escalating erosion of their infrastructure, the declining academic workforce, the
      diminishing of quality and access as a result of growing marketplace forces, and
      shrinking funds. The author provides details about the forces threatening
      academic medical centers (i.e., medical schools and their affiliated teaching
      hospitals) and then presents a variety of strategies that individual academic
      medical centers can carry out to more efficiently use their resources. But
      sufficient resources ae still needed if centers are to function as they should.
      What is to save them? The author indicates that centers should not overly depend
      on managed care, the pharmaceutical industry, or foundations to provide the
      necessary support, and that centers' internal strategies can go only so far. He
      proposes that the importance of centers and the dangers they face must be
      communicated convincingly to the nation's citizens, business leaders, government
      representatives, and purchasers of health care. The message must be repeated
      frequently so it will sink in, and must be given in terms that are relevant to
      individuals and their families. He also advises that certain types of
      partnerships may be helpful. But most critical is the need to persuade the
      government to mandate separate revenue streams for research, education, and care
      for the underserved. As hard as this will be to achieve, there are many allies of
      academic medicine, from the president to numerous legislators; the author
      discusses what they have said and done to help. He concludes by urging everyone
      in academic medicine to do their parts to make a powerful case for the value of
      academic medical centers to society, and affirms his belief that American society
      will sustain these centers.

PMID- 9040244
TI  - Finishing the bridge to diversity.
AB  - While much progress has been made to diversify the medical workforce in regard to
      gender, there is a long way to go with regard to race and ethnicity. The author
      emphasizes that seeking diversity in the medical professions is imperative to
      achieve just and equitable access to rewarding careers, improved access to health
      care for the under-served, culturally competent care (which includes the issue of
      patients' satisfaction with their care), comprehensive research agenda targeted
      to the problems of all areas of the population, and use of the rich and diverse
      pool of the nation's talent to better manage the health care system. In the 1960s
      the civil rights movement and civil unrest woke up the nation's institutions to
      the need for affirmative action initiatives, and academic medicine was one of the
      first to respond: there was a dramatic rise in the percentage of underrepresented
      minority medical school matriculants. But in the mid-1970s, this trend stalled.
      To state it again, the AAMC in 1991 created Project 3000 by 2000 as a longterm
      strategy to effect small scale educational reform in the K-12 schools and
      colleges that are responsible for the academic preparation of potential
      underrespresented-minority (URM) applicants. For a few years, the attention to
      URMs created by this program, and other factors, spurred a significant increase
      in the percentage of URM matriculants and proved the power of affirmative action.
      But the increase has not continued. The author maintains that this may be largely
      because affirmative action is being pursued with less vigor and in some cases has
      been stopped by law. He concludes with a vigorous defense of affirmative action
      and maintains that it must be used alongside more long-term solutions such as
      project 3000 by 2000 to achieve true diversity in the medical professions.

PMID- 9040245
TI  - Changing health professions education in West Virginia.
AB  - The education of students in medicine, nursing, pharmacy, and dentistry in the
      seven health professions schools of the University System of West Virginia has
      undergone remarkable changes since 1991 to become more responsive to community
      needs. The changes have also enabled the schools to remain in sync with other
      anticipated changes in health care delivery. A primary care, community-based
      academic system has been developed, and students, campus-based faculty, community
      based field professors, and lay community members collaborate to identify and
      resolve problems important to the communities located in the 42 counties
      designated Under-served Health Professions Service areas, and five additional
      rural counties. The system is governed by a board consisting of a majority of
      community members not employed by the health care system, and the deans of the
      seven health professions school; all members function as equals in reaching
      decisions. In the new system, all health professions students in the University
      System of West Virginia are required to complete a rural rotation of 12 weeks.
      The five-years demonstration project that began the new system started in 1991
      with four rural sites. By 1996, the system had expanded greatly and consisted of
      13 consortia of communities with a total of over 100 rural primary care centers
      plus several small rural hospitals, public health departments, and other health
      and social services agencies. The 1996 West Virginia legislature approved funds
      for the higher education budget that will support and sustain this primary care,
      community-based academic system.

PMID- 9040246
TI  - Implications of cognitive research for ambulatory care education.
AB  - Research in cognitive psychology has led to changes in how educators
      conceptualize thinking and approach improving students' thinking processes. As
      medical education moves into ambulatory care settings, there is an opportunity
      for educators to consider the implications of cognition theories for the
      ambulatory case curriculum. In this paper, the author briefly explains four major
      concepts of cognitive theory-the importance of context; students' need for
      transferable knowledge; the importance of balancing depth and breadth of
      knowledge; and the role of prior knowledge in problem solving- and discusses the
      possible implications of each concept for ambulatory care educations.

PMID- 9040248
TI  - David E. Rogers Award.

PMID- 9040247
TI  - Abraham Flexner Award for distinguished service to medical education.

PMID- 9040250
TI  - Alpha Omega Alpha Distinguished Teacher Award for senior faculty in the clinical
      sciences.

PMID- 9040249
TI  - Baxter Award for distinguished research in the biomedical sciences.

PMID- 9040251
TI  - Alpha Omega Alpha Distinguished Teacher Award for senior faculty in the basic
      sciences.

PMID- 9040252
TI  - Alpha Omega Alpha Distinguished Teacher Award for junior faculty in the clinical
      sciences.

PMID- 9040253
TI  - Improving America's health status through a more diverse physician workforce.

PMID- 9040254
TI  - What Americans say about the nation's medical schools and teaching hospitals.

PMID- 9040255
TI  - A predictive model of student satisfaction with the medical school learning
      environment.
AB  - PURPOSE: To examine differences in attitudes toward the medical school learning
      environment among student subgroups based on gender and race-ethnicity, to
      identify the most influential predictors of student satisfaction with the
      learning environment, and to create a model of student satisfaction with the
      learning environment. METHOD: Three years of survey data (1992-93 to 1994-95)
      from first-year students at the University of Michigan Medical School were
      combined. The total sample consisted of 430 respondents, broken into two sets of
      subgroups: women (n = 171) and men (n = 259), and whites (n = 239) and
      underrepresented minorities (n = 74). Asian students were removed from analyses
      when comparisons were made by race-ethnicity, but were included in the analyses
      for all students and those comparing men and women. Student's t-tests were used
      to identify differences between gender and racial-ethnic groups in mean responses
      to seven survey items, and effect sizes were used to characterize the magnitudes
      and practical significances of the differences. Forward stepwise regression was
      conducted to determine the best predictive models for each student subgroup and
      for the total sample; the subgroup models were compared with each other as well
      as with the total-sample model. RESULTS: Cross-validation of the gender and race
      ethnicity models showed that the men's satisfaction and the women's satisfaction
      were predicted equally well using either subgroup's model, and that the white
      students' satisfaction and the underrepresented-minority students' satisfaction
      were predicted equally well using either subgroup's model. Furthermore, the total
      sample model, employing a subset of five predictors, was similar in its
      predictive power to the subgroup models. CONCLUSION: The study's findings suggest
      that curriculum structure (timely feedback and the promotion of critical
      thinking) and students' perceptions of the priority faculty place on students'
      education are prominent predictors of student satisfaction (across all subgroups)
      with the learning environment. In contrast, students' perceptions of the learning
      environment as a comfortable place for all gender and racial-ethnic groups,
      although less prominent predictors of satisfaction, will discriminate among the
      subgroups.

PMID- 9040256
TI  - A comparison of specialty choices, residency training, and practice locations of
      early-decision and regular-admission graduates.
AB  - PURPOSE: Early-decision (ED) medical school applicants express a clear preference
      for attending a particular medical school. The present study assessed whether ED
      graduates would demonstrate similar geographic preferences in their choices of
      undergraduate institutions and selections of in-state residency sites and
      practice locations. METHOD: The study was conducted at the University of Kentucky
      College of Medicine. Uniform academic and nonacademic criteria were used to
      evaluate the applications of ED and regular-admission students who matriculated
      from 1974-75 to 1984-85. The student variables assessed were class year, gender,
      age, county of residence, and undergraduate college, as well as undergraduate
      science and cumulative grade-point averages (GPAs) and Medical College Admission
      Test (MCAT) scores. Specialty choice and locations of residency programs were
      obtained from the medical school's commencement programs. Specialty types and
      practice locations were obtained from practicing physician records maintained by
      the alumni office. RESULTS: Of the 1,243 matriculants, 193 (15.5%) gained
      admission to the school through the ED plan. The ED graduates were significantly
      more likely to have completed their undergraduate studies at the University of
      Kentucky than at other public or private schools, in state or out of state, and
      had significantly higher GPAs and MCAT scores. As a group, the ED graduates were
      somewhat (though not significantly) more likely than the regular-admission
      graduates to remain in state for their residencies and practice in state.
      CONCLUSION: The authors suggest that medical schools should work closely with
      their undergraduate admission offices to attract academically outstanding high
      school students. Such students are likely to stay in state for the eight-year
      span of their undergraduate and medical educations and may have a greater
      tendency to practice in state.

PMID- 9040257
TI  - Three medical schools' responses to the HIV/AIDS epidemic and the effect on
      students' knowledge and attitudes.
AB  - PURPOSE: To assess the relative importance of factors influentail by the
      prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS), such as didactic and clinical training, and the number of HIV
      infected individuals known personally, on students' HIV-related knowledge and
      attitudes. METHOD: A survey was undertaken of the classes of 1991 and 1994 at the
      University of Colorado School of Medicine, the University of New Mexico School of
      Medicine, and the University of South Dakota School of Medicine. The
      questionnaire contained 40 knowledge questions, 20 attitude questions, and
      demographic questions. The students reported estimates of HIV-related didactic
      hours and clinical encounters experienced during their training, as well as the
      number of HIV-infected individuals known personally. Data analysis employed two
      way analysis of variance (ANOVA) and Pearson correlation coefficients. RESULTS:
      In 1991 the response rates were 73% from Colorado, 54% from New Mexico, and 50%
      from South Dakota; in 1994 the rates were 80%, 63%, and 60%, respectively.
      Training programs were similar between schools and over time, varying only in the
      amounts of didactic information offered. The 1994 students scored significantly
      better than did 1991 students on knowledge, overall attitude, fear of infection,
      and willingness to treat HIV-infected patients; these variables were
      significantly correlated with the numbers of HIV-infected individuals known
      personally by the students. Didactic training hours were not significantly
      correlated with any study variable, and clinical experiences were correlated only
      with increased knowledge. CONCLUSION: Differences in HIV/AIDS prevalences did not
      affect the schools' training programs, but indirectly affected the students'
      knowledge and attitudes, which were related to the numbers of HIV-infected
      individuals known personally by the students. The authors recommend that medical
      schools increase students' opportunities for meaningful personal contact with HIV
      infected individuals.

PMID- 9040259
TI  - Interrater concordance for faculty grading of student performances in a problem
      based learning course.
AB  - PURPOSE: To determine whether it is possible for faculty to arrive at consistent,
      non-idiosyncratic grades in a problem-based learning (PBL) course. METHOD:
      Integrated Case Studies and Medical Decision Making (ICS) is the final course of
      the second year at the University of Pittsburgh School of Medicine. In ICS, 16
      groups of nine students work in a PBL format over seven weeks. Each group is led
      by three faculty facilitators who, at the end of the course, independently give
      each student ratings for overall performance in the course and for each of seven
      performance categories. In 1993-94 and 1994-95, concordance in grades among the
      facilitators was determined by computing the intraclass correlation coefficients
      [ICC (3,1)] for the overall scores, the seven performance category scores, and
      all eight scores in aggregate. An ICC (3,1) of > or = .1 was considered
      indicative of statistically significant interrater concordance. An ICC (3,1) of >
      or = .7 was considered indicative of concordance of practical significance.
      RESULTS: Because the facilitators occasionally did not rate every student in
      every performance category, complete information was not available for all 32
      groups. Statistically significant concordance was achieved in the aggregate
      scores in 100% of 23 groups, and in the overall scores in 90% of 18 groups. In
      six of the seven performance categories, concordance was achieved in at least 75%
      of the groups (n = 16-20). Practically significant concordance was achieved in
      the aggregate scores in 83% of 23 groups. CONCLUSION: The study results show
      that, given specific criteria by which to judge students' performances, it is
      possible to arrive at consistent, non-idiosyncratic grades for students in PBL
      courses.

PMID- 9040258
TI  - The effect of an ambulatory internal medicine rotation on students' career
      choices.
AB  - PURPOSE: To assess the effect of an ambulatory care experience on medical
      students' perceptions of internal medicine and their choices of careers (as
      measured by residency selections). METHOD: In 1990-91, the 196 third-year
      students enrolled in the 12-week internal medicine clerkship at the University of
      Texas Medical School at San Antonio were randomized to a curriculum that included
      a three-week ambulatory care component or to a traditional, exclusively inpatient
      curriculum. The ambulatory curriculum included the evaluation of walk-in
      patients, exposure to community internists, and a lecture series. The students'
      perceptions of internal medicine were surveyed before and after the clerkship.
      Their career choices were determined by their residency selections at graduation.
      Data analysis employed chi-square tests, t-tests, and logistic regression.
      RESULTS: Of the 196 students, 184 (76 in the ambulatory and 108 in the
      traditional curricula) provided complete data. The ambulatory care students were
      somewhat more likely to enter an internal medicine residency (odds ratio = 1.49;
      95% CI, 0.72 to 3.09) than were the traditional students. The ambulatory care
      students' perceptions of internal medicine did not change significantly from
      before to after the clerkship. CONCLUSION: The ambulatory curriculum had a modest
      but favorable effect on the students' selections of careers in internal medicine,
      but was not associated with changes in their perceptions of internal medicine.

PMID- 9040260
TI  - Internal medicine residents' assessment of the subspecialty fellowship
      application process.
AB  - PURPOSE: The application process for fellowships in internal medicine
      subspecialties begins approximately 18 to 24 months before the start of training,
      requiring residents to decide on a career by the beginning of their second year
      of residency. The authors surveyed the internal medicine residents at Mount Sinai
      Hospital to assess their attitudes toward the fellowship application process.
      METHOD: A survey instrument was designed and given to all 121 residents in 1994
      95. The instrument surveyed the residents' career plans and the timing of their
      decisions, inquired about the effect on their residency of applying for a
      fellowship, and asked the residents to assess and comment on the timing of the
      fellowship application process. RESULTS: In all, 80% (97) of the residents
      responded. Nearly two-thirds intended to apply for fellowship training; however,
      17% of the first-year residents had changed their minds about their fellowship
      plans, and 50% of the second- and third-year residents had changed career plans.
      Whereas 79% of the first-year residents intended to apply "on time" during their
      second year, only 29% of the second-year residents intended to do so; 25% of the
      third-year residents planned to delay entry into a fellowship. Nearly two-thirds
      of the first- and second-year residents felt uncomfortable making an informed
      fellowship decision in their second year. In all, 60% of the residents felt they
      had to do research in order to get a competitive fellowship, and 68% said they
      had to change their assigned residency schedule to "get credentials" for
      fellowship applications. The consensus of nearly all the residents was that the
      timing of fellowship applications was much too early and should be moved to the
      middle of the third year. CONCLUSION: As the current system of applying for
      medical fellowships is generally experienced negatively by residents, the authors
      recommend that the process be moved to the middle of the third year and that
      medical schools, residency programs, and fellowship training programs reconsider
      the entire fellowship application process.

PMID- 9040262
TI  - Orthopaedic proceedings and dissertation, 1995, 1996. Abstracts.

PMID- 9040261
TI  - Family medicine residents' and community physicians' concerns about patient
      truthfulness.
AB  - PURPOSE: To assess how often family physicians question patient truthfulness,
      what factors influence them to do so, and how often resident physicians
      experience such doubts as compared with senior physicians. METHOD: In 1994-95,
      after half-day patient care sessions, 44 residents from the University of Kansas
      School of Medicine's three Wichita family practice residency programs and nine
      community family physicians associated with the programs recorded their
      impressions of each patient's truthfulness, what issues prompted concern about
      patient truthfulness, and their feelings about each encounter. RESULTS: The
      residents doubted patients in 54 of 277 encounters (19.5%); the senior physicians
      doubted patients in 16 of 183 encounters (8.7%) (p = .003). Both groups had more
      negative than positive emotions toward such encounters, with no significant
      difference in feelings. The demographics of the resident and senior physician
      populations differed greatly. CONCLUSION: Although preliminary, the present study
      suggests that family physicians question patient truthfulness fairly often,
      resident physicians more than senior physicians, and that these physicians have
      some negative feelings toward such situations. Because such feelings may
      contribute to inadequate patient care, the authors recommend that further
      research is warranted to understand contributing factors and to guide the
      development of resident and student education programs in this neglected area of
      the doctor-patient relationship.

PMID- 9040263
TI  - Hemodynamic consequences of stenosis remodeling during coronary angioplasty.
AB  - Quantitative hemodynamic assessment during various endovascular interventions
      including balloon angioplasty is lacking. Translesional pressure drops measured
      by angioplasty catheters can cause flow blockage and thus lead to inaccurate
      estimates of preintervention and postintervention flow rates. A new analytical
      model of the flow rate-pressure drop relation across vascular stenoses is
      utilized that is nonlinear yet relatively simple in principle, easily applicable
      in vivo, and compatible with the presence of catheters. The model incorporates in
      vitro experimental evidence, angiographic data on the dimensions and shapes of
      coronary arterial stenoses before and after balloon angioplasty, reported
      translesional pressure gradients, and measurements of coronary flow reserve.
      Reasonable estimates of mean coronary artery flow rates and translesional
      pressure drops in the absence of angioplasty catheters are obtained. Prior to
      angioplasty significant flow restriction across a 68% diameter stenosis exists
      during hyperemic flow conditions. Following successful balloon dilation,
      increased minimal cross-sectional area (residual 40% diameter stenosis) results
      in an improved flow rate-pressure drop relation. Despite minimal flow restriction
      during hyperemic conditions following angioplasty remodeling, residual luminal
      constriction leads to elevated wall shear stress levels within the entry region
      of the stenosis. The flow analysis described may be of clinical utility in
      evaluating the hemodynamic significance of the anatomic severity of stenoses in
      coronary and peripheral arteries before and after endovascular therapeutic
      interventions.

PMID- 9040264
TI  - Is there any association between dissection after successful percutaneous
      transluminal coronary angioplasty and late restenosis? An angiographic study.
AB  - Restenosis continues to be the most important limitation of percutaneous
      transluminal coronary angioplasty (PTCA). Many clinical, angiographic, and
      procedural variables are thought to be related to the development of restenosis.
      This study was aimed at investigating the effects of no dissection, minor
      dissections, and major dissections on the long-term outcome of lesions after
      successful PTCA. The study group comprised 91 patients with 100 lesions who
      underwent successful PTCA and in whom follow-up coronary angiography was
      performed at 8.8 +/- 7.2 (two to twenty-three) months after dilation. Dissections
      were classified according to the National Heart, Lung, and Blood Institute
      criteria. Restenosis was defined as more than 50% stenosis at follow-up
      angiography. Restenosis rates were found to be 22% in the no-dissection group (10
      restenoses in 46 patients), 27% in the minor dissection group (11 restenoses in
      40 patients), and 36% in the major dissection group (5 restenoses in 14
      patients). The authors applied corrected Yates Chi-square test and no difference
      was observed in the restenosis rate between the group without any dissections and
      that with minor dissections (P > 0.05). However, a statistically significant
      difference was observed in the restenosis rate between the major dissection group
      and the other two groups (P < 0.05). The authors conclude that the occurrence of
      major dissections after successful PTCA may adversely affect the long-term
      outcome and may increase the restenosis rate.

PMID- 9040265
TI  - Catheter fragments embolization.
AB  - Although the use of central venous silicone catheters is widespread, little is
      known about the incidence of catheter rupture and embolization. Over a three-year
      period, 3916 silicone catheters were inserted in 3672 patients in the authors'
      hospital. Catheter or catheter fragments embolism occurred in 4 patients (1.2
      embolizations per 1000 patients treated). Inappropriate mechanical deobstruction
      attempts resulted in 2 embolizations, and hence, these should be avoided. Chest
      roentgenography failed to detect the small fragments within the heart silhouette
      in 2 cases. Two-dimensional echocardiography showed the separated catheter
      fragment in all 4 cases. All four catheter fragments were subsequently removed
      from the right-heart chambers.

PMID- 9040266
TI  - Use of a collagen plug versus manual compression for sealing arterial puncture
      site after cardiac catheterization.
AB  - The aim of the study was to investigate (1) the safety and efficacy of the
      application of a collagen plug (Vasoseal) at arterial puncture sites, (2) the
      hemostasis time, and (3) the comfort for the patient of a collagen plug
      (Vasoseal) when compared with manual compression. Sixty-two patients were
      randomized either for application of a collagen plug (Vasoseal, group A, n = 33)
      or manual compression (group B, n = 29) after cardiac catheterization. All
      patients were evaluated for subjective pain score ranging from 1 to 5 (1 = no
      pain up to 5 = very strong pain). In addition the authors measured the time until
      hemostasis could be achieved. The patients were evaluated by duplex sonography
      for complications at days 1 and 7 after the procedure. The pain score
      demonstrated a significantly lower score in group A when compared with group B (P
      = 0.01). The mean time for hemostasis was significantly lower in group A (mean
      9.6 minutes) when compared with group B (mean 23.6 minutes) (P = 0.0001).
      Regarding the complication rate there was no significant difference between the
      groups (group A vs group B, P = 0.82). The authors conclude that the application
      of a collagen plug at the arterial puncture site is a safe and time-saving
      method. In addition it is less painful and therefore better tolerated than manual
      compression.

PMID- 9040267
TI  - Stress echocardiography using adenosine combined with nitroglycerin-dobutamine in
      the detection of viable myocardium in patients with previous myocardial
      infarction.
AB  - The aim of this study was to assess the value of adenosine (A) and the
      combination of nitroglycerin (N) with dobutamine (D) stress echocardiography (SE)
      in the identification of viable myocardium. The clinical and electrocardiographic
      (ECG) effects of both tests were also evaluated. Fifty-two coronary artery
      disease patients, aged 56.4 +/- 8 years, with left ventricular dysfunction due to
      a previous myocardial infarction (mean ejection fraction: 49 +/- 8%) were
      included in the study. Cardiac catheterization was performed in all patients
      before A (140 micrograms/kg/minute for five minutes) and the combination of N
      with D (5-10 micrograms/kg/minute) stress echocardiography. On the
      echocardiogram, the left ventricle was divided into 16 segments and wall motion
      was graded semiquantitatively from 1 (normal) to 4 (dyskinesia). The
      echocardiographic index was also estimated. A segment was considered viable
      during A infusion when resting asynergy showed deterioration of one grade or
      more. In contrast, segmental viability was considered to be present during the
      combination of N with D infusion when resting asynergy showed improvement of one
      grade or more. A thallium 201 single photon emission computed tomography (SPECT)
      with reinjection was performed as reference standard for the identification of
      viable myocardium. Stress echocardiography during infusion of A was associated
      with short-duration angina attacks in 3 (5.8%) patients and transient complete
      atrioventricular (AV) block in 1 (1.9%), whereas during the combination of N with
      D infusion, 6 (11.5%) patients experienced ventricular bigeminy lasting for a
      short period. ST segment elevation greater than 1 mm was recorded in those leads
      having a Q wave, in 19 (36.5%) patients. In 10 of these 19 (52.6%), viable
      myocardium was present in SPECT, as it was in 33 patients (63.5%) having no ST
      segment elevation (P = NS). Of a total of 832 segments that were graded during A
      SE, 276 exhibited resting asynergy and the remaining 556 had normal motion and
      thickening at rest. The echocardiographic index during A infusion increased from
      1.52 +/- 0.22 to 1.71 +/- 0.24 (P < 0.001), whereas during D and N infusion it
      decreased from 1.53 +/- 0.31 to 1.30 +/- 0.42 (P < 0.001). With SPECT considered
      as the gold standard for the identification of viable myocardium, sensitivity,
      specificity, and positive and negative predictive values of A-SE in detecting
      viable myocardium were 54%, 86%, 65% and 80%, respectively. The respective values
      for the combination of nitroglycerin with D-SE were 91%, 89%, 78%, and 96%,
      respectively. Stress echocardiography during A, and the combination of N with D,
      constitute safe methods in the identification of viable myocardium. The detection
      of ST segment elevation in the ECG leads with a Q wave during the combined
      infusion of nitroglycerin and dobutamine is not related to the presence of viable
      myocardial tissue. The A-SE provide moderate diagnostic accuracy, while the
      combination of N with D during SE is much superior in detecting viable
      myocardium.

PMID- 9040268
TI  - Determinants of exercise-induced ST segment depression in patients with coronary
      artery disease: a multivariate approach.
AB  - The purpose of this study was to delineate among the usually gathered parameters
      in an electrocardiographic exercise test the determinants of its positive outcome
      (delta ST decreases > or = 1 mm measured at 80 msec from the J point). The
      authors studied 832 patients investigated with Bruce's exercise testing and with
      diagnostic coronary arteriography, all of whom were shown to have significant
      coronary artery disease (diameter stenosis > or = 50%). Twenty-five demographic,
      clinical, electrocardiographic, exercise, and anatomic/hemodynamic parameters
      were analyzed. The stepwise forward logistic regression analysis retained seven
      among them as significant independent predictors: four as positive contributors:
      (1) three-vessel and/or left main disease (P = 0.0000), (2) Gensini's angio
      graphic score for disease extent (P = 0.0025), (3) anginal pain during the test
      (P = 0.0000), and (4) age (P = 0.0031) and three as negative contributors: (1)
      resting heart rate (P = 0.0004), (2) history of old myocardial infarction (P =
      0.0019), and (3) pathological Q waves at the resting ECG (P = 0.0018). These
      findings establish standards that permit the prediction of the positive
      electrocardiographic exercise outcome in patients with significant coronary
      disease.

PMID- 9040269
TI  - Synergism of hemopoietic growth factors on endothelial cell proliferation.
AB  - Endothelial cells, which are nonhemopoietic cells, express and/or produce most of
      the known hemopoietic receptors and cytokines. The biological role of these
      factors, and their respective receptors, on endothelial cells is still unknown.
      In this study, the authors assessed the effect of different hemopoietic growth
      factors, ie, interleukin-3 (IL-3), erythropoietin (EPO), macrophage-colony
      stimulating factor (M-CSF), granulocyte-colony stimulating factor (G-CSF),
      granulocyte macrophage-colony stimulating factor (GM-CSF), singly or in
      conjunction with others, on proliferation and chemotaxis of human umbilical vein
      endothelial cells (HUVECs). They found growth stimulatory activity with IL-3,
      EPO, and GM-CSF and potent synergism between EPO and IL-3, less with IL-3 and GM
      CSF, and none with EPO and either GM-CSF or G-CSF. All the singly tested
      hemopoietic growth factors stimulated the migration of HUVECs, but in conjunction
      with other factors, they did not show any additive or synergistic effect.

PMID- 9040270
TI  - Postischemic hyperemia in subjects with lower limbs obstructive arteriopathy:
      role of PGI2 and endothelin.
AB  - The physiological basis of postischemic hyperemia is not yet fully understood.
      The present study investigated the effects of pharmacologic manipulation of the
      prostaglandin system on local hemodynamics. Strain-gauge plethysmography was used
      to study 8 normal subjects and 9 patients with obliterating arterial disease of
      the lower limbs. Hemodynamic evaluations were performed before treatment, after
      seven days of low-dose acetylsalicylic acid (100 mg/day) to inhibit platelet
      thromboxane synthesis, and after acute infusion of 1 g of acetylsalicylic acid to
      inhibit endothelial prostacyclin synthesis. In patients with arterial disease,
      the hemodynamic study was also carried out after infusion of iloprost, a
      synthetic prostacyclin analogue. Acute infusion of acetylsalicylic acid
      significantly reduced basal blood flow in normal subjects, but not in patients
      with arterial disease. In the latter group, iloprost affected neither basal nor
      maximal postischemic flow. The study also evaluated the role of endothelin in
      musculocutaneous hemodynamic regulation, both in physiological conditions and in
      atherosclerosis. This part of the study addressed the possibility that the
      hemodynamic effects of vasodilator prostanoids like prostacyclin might affect
      endothelin release in vivo. During reactive hyperemia, plasma endothelin was
      reduced in normal subjects (-1.02 pg/mL, 95% CI: -2.23, 0.08), but not in
      patients with atherosclerosis (-0.35 pg/mL, 95% CI: -1.45, 0.75). In both groups,
      plasma endothelin was not affected by aspirin. These findings confirm the role of
      prostacyclin in local hemodynamic regulation. In the normal subject,
      musculocutaneous blood flow seems to depend at least in part on the action of
      vasodilator prostanoids and endothelin. This is not the case in patients with
      arterial disease, in whom plasma endothelin does not seem to be affected by
      postischemic changes in blood flow. A possible explanation for this difference
      could be alteration of the endothelial function in patients with arterial
      disease, related to the functional and structural characteristics of the artery
      wall in atherosclerosis.

PMID- 9040271
TI  - Physical therapy improves venous hemodynamics in cases of primary varicosity:
      results of a controlled study.
AB  - Physical factors are known to influence hemodynamics in the veins of the lower
      extremities. In a controlled, randomized study the authors investigated the
      effects of combined physical therapy on varicose veins. Over a twenty-four-week
      period a treatment group consisting of 12 persons exercised under the supervision
      of a therapist twice a week for sixty minutes. This included muscle and joint
      activation by means of externally applied compression and cold-temperature
      stimuli (ie, thermosteresis). They also exercised once a day without supervision
      for fifteen minutes. During the same period a control group of 12 persons
      underwent the same measurements but no treatment. In the treatment group venous
      capacity decreased by an average of 16% from 4.9 +/- 0.3 (sd) mL/100 mL tissue to
      4.1 +/- 0.4 (P < 0.005, U-test) while in the control group it remained
      practically unchanged at 4.8 +/- 0.4 vs 5.0 +/- 0.3. Venous refilling time in the
      lower extremities also increased in the treatment group, half refilling time
      rising from 7.8 +/- 1.0 to 11.3 +/- 0.9 seconds (P < 0.001) and total refilling
      time from 17.0 +/- 1.4 to 25.7 +/- 2.1 seconds (P < 0.001); these parameters
      remained virtually unchanged in the control group, with half refilling time
      dropping slightly from 7.7 +/- 1.1 to 7.1 +/- 1.3 seconds and total refilling
      time from 18.3 +/- 1.7 to 16.3 +/- 1.9 seconds. Patient self-rating scores
      obtained by use of a standardized questionnaire administered at baseline and at
      the end of week 24 improved in the treatment group only. The combined physical
      therapy was thus shown to be of long-term therapeutic value, improving venous
      function and reducing patients' symptoms. These findings indicate that for the
      further development of this combined treatment regimen it would be useful to
      identify the individual factors contributing to its efficacy and evaluate them
      separately.

PMID- 9040272
TI  - Survival following cardiogenic shock caused by acute left main coronary artery
      total occlusion. A case report and review of the literature.
AB  - The authors describe a fifty-five-year-old Japanese man with an acute extensive
      anterior myocardial infarction associated with a total occlusion of the left main
      coronary artery. The patient suffered cardiogenic shock and was treated
      successfully with rescue percutaneous transluminal coronary angioplasty and an
      intraaortic balloon pump (IABP) after unsuccessful intracoronary thrombolysis.
      Ten days after admission, he was weaned from IABP, and recovery-phase coronary
      angiography revealed no significant coronary artery stenosis and an ejection
      fraction of 32% by left ventriculography. The patient was discharged from the
      hospital without any ischemic findings.

PMID- 9040273
TI  - Cholestyramine therapy for quinidine-induced diarrhea. Case reports.
AB  - The effective use of quinidine as an antiarrhythmic agent is frequently curtailed
      by one of its most common side effects-relentless diarrhea. Seven patients are
      described in whom diarrhea was quickly and completely controlled by the use of
      cholestyramine resin. To date, this is the only therapy reported to be effective
      for this purpose. It has proven to be safe, well tolerated, and continuously
      effective in these cases.

PMID- 9040274
TI  - Left ventricular pseudoaneurysm presenting twenty-eight months after myocardial
      infarction. A case report.

PMID- 9040275
TI  - Primary antiphospholipid syndrome and pulmonary hypertension with prolonged
      survival. A case report.
AB  - The outcome of patients with pulmonary hypertension (PHT) and antiphospholipid
      syndrome (APS) is usually fatal. The authors report the rare case of a patient
      with primary APS and nonthrombotic PHT who has survived for twenty years after
      the onset of PHT. In this case, the patient's PHT resembled the primary
      idiopathic variety with clear lung fields and normal perfusion on the lung scan,
      and the combination therapy with nitrate, digoxin, and diuretics had been
      performed. During her clinical course over twenty years, she had not experienced
      any critical pulmonary thrombosis that influenced the progression of
      nonthrombotic PHT or any other severe systemic involvement of APS.

PMID- 9040276
TI  - Research with cognitively impaired subjects. Unfinished business in the
      regulation of human research.
AB  - In 1978, the National Commission for the Protection of Human Subjects of
      Biomedical and Behavioral Research issued an important report that addressed the
      difficult ethical issues arising in research involving subjects with mental
      disabilities. However, because of irreconcilable conflicts between the scientific
      community and rights-oriented advocacy groups, the federal government never
      issued the special regulations pertaining to these issues that had been
      envisioned by the National Commission. Because these important ethical issues
      have not yet been adequately addressed by policy-making bodies, protection of
      cognitively impaired subjects depends too heavily on the diverse ethical
      sensitivities of individual investigators and on ad hoc responses of particular
      institutional review boards. Researchers should support a credible and
      authoritative process for reexamining and resolving ethical issues relating to
      research with cognitively impaired subjects. This can be accomplished without
      leading to the stalemate that doomed the National Commission's proposals. The
      challenge is to forge a consensus on ethical guidelines and safeguards that will
      most reasonably accommodate the goals of protecting the dignity and well-being of
      research subjects while avoiding undue impediments to valuable scientific
      inquiry.

PMID- 9040277
TI  - Caring about risks. Are severely depressed patients competent to consent to
      research?
AB  - Depressed patients are often asked to take part in clinical research studies that
      carry risk. These patients are generally assumed to be mentally competent to
      consent to research, since depression often leaves a patient's cognitive
      abilities intact. In this article, it is argued that many severely depressed
      patients may not be competent to consent because they cannot be considered
      accountable for their decisions. The article presents 2 arguments: first, that it
      is unclear whether the decisions of some severely depressed patients are
      authentically theirs, and second, that some severely depressed patients may not
      have the appropriate minimal degree of concern for their own well-being. It is
      argued that assessments of competence must take account of emotional factors, and
      that, if severely depressed patients are incompetent to consent, research studies
      involving a poor risk-benefit ratio will be much more difficult to justify.

PMID- 9040278
TI  - Rethinking the conduct of psychiatric research.

PMID- 9040279
TI  - Protecting subjects and fostering research. Striking the proper balance.
AB  - Bonnie reminds us of the heritage and limitations of human subjects research. He
      points out that over the years, the protection of human subjects in research has
      enjoyed progress, experienced false starts, and endured inflated expectations.
      Both he and Elliott call attention to the fact that IRB review rarely probes how
      researchers propose to deal with impairments to subjects' decision-making
      capacities. We agree to IRBs should be encouraged to rethink their roles. But, as
      Bonnie argues, this requires a systematic review of the roles and functions of
      IRB rather than ad hoc adjustments by individual institutional IRBs. His proposal
      that IRBs should be encouraged to be more vigilant and through in their
      monitoring of research is sound, especially if the subjects are vulnerable or the
      research is risky. A strength of Bonnie's review is that it suggests both
      specific ways to test competency and a range of options for IRBs to ensure that
      vulnerable subjects are protected from overzealous or overreaching researchers.
      His historical review and normative proposals are objective, balanced, and
      thoughtful. Elliott's critique seems to single out psychiatric research with
      depressed patients as a special problem area. Although his title emphasizes
      severely depressed patients, he sometimes appears to neglect the fact that
      depression ranges across a spectrum from mild to severe. Elliott's point is well
      taken that severely depressed patients who are clearly incompetent should not,
      unless proper safeguards are provided, be enrolled in research. But his analysis
      falters because his position does not in the end respect personal autonomy.

PMID- 9040280
TI  - Circadian rest-activity disturbances in seasonal affective disorder.
AB  - BACKGROUND: Previous studies hypothesized that seasonal affective disorder (SAD)
      was caused by a circadian rhythm abnormality. The purpose of this study was to
      ascertain whether rest-activity rhythms were phase delayed, diminished in
      amplitude, or more poorly entrained to the 24-hour day. METHOD: Twenty healthy
      adult controls and 25 outpatients meeting Rosenthal-National Institute of Mental
      Health criteria for SAD and DSM-III-R criteria for major or bipolar depression
      with seasonal pattern had their levels of activity recorded for 72 hours
      (weekdays) using wrist-worn actigraphs. RESULTS: Subjects with SAD had activity
      levels that were 11% lower than controls (P = .03), and their levels of activity
      were most attenuated during the first 2 hours after arising (P = .004). The
      relative amplitude of the circadian rhythm did not differ between groups.
      Patients with SAD were phase delayed by 50 minutes for the entire period (P =
      .02). Analysis of each individual day indicated that patients were delayed by up
      to 70 minutes (P = .007). Interdaily stability, an index of coupling between the
      rhythm and its zeitigeber was reduced in SAD (P = .01). Compared with controls,
      patients with SAD had best-fit circadian periods that were 92% more deviated from
      24 hours (P = .007) and daily acrophase (time of the peak of the fit circadian
      rhythm) times that were 110% more variable between days (P < .001). CONCLUSIONS:
      Patients with SAD have circadian rest-activity rhythms that are significantly
      phase delayed and more poorly entrained to the 24-hour day.

PMID- 9040281
TI  - Effects of tryptophan depletion on drug-free patients with seasonal affective
      disorder during a stable response to bright light therapy.
AB  - BACKGROUND: A dysfunction of the serotonin system may play a major role in the
      pathogenesis of seasonal affective disorder. Bright light therapy has been shown
      to be effective in the treatment of winter depression in patients with seasonal
      affective disorder. Light therapy-induced remission from depression may be
      associated with changes in brain serotonin function. METHODS: After at least 2
      weeks of clinical remission, 12 drug-free patients who had had depression with
      seasonal affective disorder underwent tryptophan depletion in a double-blind,
      placebo-controlled, balanced cross-over design study. RESULTS: Short-term
      tryptophan depletion induced a significant decrease in plasma free and total
      tryptophan levels (P < .001 for both, repeated measures analysis of variance),
      with peak effects occurring 5 hours after ingestion of a tryptophan-free amino
      acid drink. It emerged that tryptophan depletion leads to a transient depressive
      relapse, which was most pronounced on the day after the tryptophan-depletion
      testing. No clinically relevant mood changes were observed in the control
      testing. CONCLUSIONS: The maintenance of light therapy-induced remission from
      depression in patients with seasonal mood cycles seems to depend on the
      functional integrity of the brain serotonin system. Our results suggest that the
      serotonin system might be involved in the mechanism of action of light therapy.

PMID- 9040282
TI  - Complex interaction of the sleep-wake cycle and circadian phase modulates mood in
      healthy subjects.
AB  - BACKGROUND: Several studies of healthy volunteers have revealed that subjective
      mood may vary with the duration of prior wakefulness and with the time of day.
      However, in these studies, the effects of extended wakefulness and circadian
      phase remained confounded, and the interaction of these 2 processes could not be
      assessed quantitatively. METHODS: In the present study, a total of 24 healthy
      young subjects (16 men, 8 women) lived on a 30-hour sleep-wake schedule for 19 to
      23 days or on a 28-hour sleep-wake schedule for 33 to 36 days; both schedules
      induced desynchrony between the subjects' sleep-wake cycle and their endogenous
      circadian pacemaker. Subjective mood was assessed by 2 types of visual analog
      scales, which were administered twice every 2 hours and every 20 minutes,
      respectively, during all scheduled wakefulness episodes. A circadian phase and an
      interval elapsed since awakening were attributed to each data point, and
      circadian and wake-dependent fluctuations of mood were assessed. RESULTS: A
      significant variation of mood with circadian phase was observed, but no reliable
      main effect of the duration of prior wakefulness was found. A statistically
      significant interaction of circadian and wake-dependent fluctuations was evident;
      when the analysis was restricted to specific circadian phases, mood improved,
      deteriorated, or remained stable with the duration of prior wakefulness.
      CONCLUSIONS: These results indicate that, in healthy young subjects, subjective
      mood is influenced by a complex and nonadditive interaction of circadian phase
      and duration of prior wakefulness. The nature of this interaction is such that
      moderate changes in the timing of the sleep-wake cycle may have profound effects
      on subsequent mood.

PMID- 9040283
TI  - Reduced blue cone electroretinogram in cocaine-withdrawn patients.
AB  - BACKGROUND: The main reinforcing effect of cocaine is alteration of dopaminergic
      neurotransmission in the brain reward systems. Since dopamine is found in high
      concentrations in the retina, we investigated whether cocaine dependence may be
      associated with abnormalities of the electroretinogram. METHODS: We compared
      recently withdrawn cocaine-dependent patients (n = 20) with age-, sex-, and race
      matched normal subjects (n = 20) for responses of cone photoreceptors to light
      flashes on full-field electroretinograms. RESULTS: Cocaine-dependent patients had
      significantly reduced blue cone electroretinogram responses compared with matched
      normal subjects. CONCLUSIONS: This result suggests that cocaine-withdrawn
      patients have a dysregulation of blue cone function. The electroretinogram may be
      useful in future studies of cocaine-dependent patients.

PMID- 9040284
TI  - Auditory working memory and Wisconsin Card Sorting Test performance in
      schizophrenia.
AB  - BACKGROUND: Impaired Wisconsin Card Sorting Test (WCST) performance has been one
      critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia.
      However, the specific cognitive processes underlying impaired performance have
      not been identified. Impaired WCST performance in schizophrenia might in part
      reflect a fundamental working memory deficit. METHODS: We examined the
      performance of 30 normal subjects and 36 patients with schizophrenia on a
      neuropsychological battery including a novel measure of working memory-letter
      number (LN) span. RESULTS: Patients with schizophrenia were impaired on LN span
      performance, which was also highly correlated with WCST performance (r = 0.74).
      Between-group WCST differences were eliminated when we covaried LN span.
      Regression analyses suggested that LN span performance predicted the WCST
      category achieved score, whereas measures of set shifting, verbal fluency, and
      attention were predictive of perseveration. CONCLUSION: Working memory may be a
      critical determinant of one aspect of WCST performance in schizophrenia.

PMID- 9040285
TI  - Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of
      patients with schizophrenia.
AB  - BACKGROUND: Biological relatives of patients with schizophrenia demonstrate an
      increased prevalence of schizotypal personality disorder symptoms, eye tracking
      deficits, and attentional disturbances. We investigated whether these
      hypothesized components of a schizophrenia-related phenotype are associated with
      one another or are independent in nonpsychotic relatives of patients with
      schizophrenia. METHODS: Eighty-three nonpsychotic first-degree relatives of 38
      patients with schizophrenia and 45 control subjects without a psychiatric
      diagnosis underwent clinical evaluation, eye tracking evaluation, and the
      Continuous Performance Test (CPT) of visual attention. RESULTS: Eye tracking
      qualitative rating was more powerful than quantitative eye tracking measures or
      CPT measures in discriminating relatives of patients with schizophrenia from
      control subjects. Correlations between neurocognitive variables and DSM-III-R
      schizotypal personality disorder symptom clusters suggested that CPT errors of
      omission are associated with positive schizotypal symptoms. Eye tracking measures
      were not significantly correlated with schizotypal symptoms or CPT errors in
      relatives of patients with schizophrenia. CONCLUSIONS: Eye tracking deficits in
      the relatives of patients with schizophrenia are unrelated to CPT deficits and
      schizotypal symptoms. Eye tracking deficits and disturbances in visual attention
      may be separate components of a schizophrenia-related phenotype and should be
      considered as independent factors in genetic studies of schizophrenia.

PMID- 9040286
TI  - Temperance board registration for alcohol abuse in a national sample of Swedish
      male twins, born 1902 to 1949.
AB  - BACKGROUND: Temperance boards were established in Sweden to register and follow
      up individuals who were seen in legal or medical settings with problems of
      alcohol abuse. These records, available in a large epidemiologic twin population,
      have provided an objective and validated measure of alcohol abuse. METHODS: We
      examined Swedish temperance board registrations from 1929 to 1974 (n = 2516
      individual twins) in all male-male Swedish twin pairs of known zygosity from the
      population-based Swedish Twin Registry; these twin pairs were born from 1902 to
      1949 (n = 8935 pairs). RESULTS: The lifetime prevalence and probandwise
      concordance rates for temperance board registrations were 13.2% and 47.9%,
      respectively, in monozygotic twins and 14.6% and 32.8%, respectively, in
      dizygotic twins. Model fitting suggested that genetic and familial-environmental
      risk factors accounted for 54% (95% confidence interval [CI], 47%-61%) and 14%
      (95% CI, 8%-19%) of the liability to temperance board registration, respectively;
      these estimates were stable across birth cohorts. High genetic liability was
      reflected by large numbers of temperance board registrations and registrations
      for criminal alcohol use. Elevated familial-environmental liability was indicated
      by an early age at first registration. CONCLUSIONS: Genetic factors are of major
      etiologic importance for alcohol abuse in men, while familial environmental
      factors play a significant but less important role. The etiologic importance of
      these factors has remained constant in Sweden for men who were born in the first
      half of the 20th century.

PMID- 9040287
TI  - Phosphorus 31 magnetic resonance spectroscopy in patients with Huntington
      disease.

PMID- 9040288
TI  - Use of methylphenidate in a patient with glaucoma and attention-deficit
      hyperactivity disorder: a clinical dilemma.

PMID- 9040289
TI  - Sex differences in schizophrenia.

PMID- 9040290
TI  - Home access HIV testing. What took so long?

PMID- 9040291
TI  - A free-floating approach to filters.

PMID- 9040292
TI  - Helicobacter pylori infection and anorexia of aging.

PMID- 9040293
TI  - Evidence-based, cost-effective risk stratification and management after
      myocardial infarction. California Cardiology Working Group on Post-MI Management.
AB  - Current management of patients after an acute myocardial infarction (AMI)
      reflects a variety of approaches ranging from conservative to aggressive.
      Although each method is appropriate in certain subgroups, their application
      frequently lacks a scientific basis. Current, clinically relevant, evidence-based
      practice guidelines are needed for secondary prevention for survivors after an
      AMI. To meet this need, the California Cardiology Working Group was assembled to
      evaluate the available data from clinical trials and other published studies and
      develop evidence-based, cost-effective guidelines for clinicians to use as a
      basis for patient management after an AMI. The group consisted of 18 members,
      including cardiologists from academic institutions and physicians working in
      cardiac intensive care, private practices, and managed care settings,
      representing a broad spectrum of expertise pertaining to patients who have had an
      AMI. The members had expertise in cardiac intensive care, interventional
      cardiology, nuclear cardiology, lipid disorders, echocardiography, and cardiac
      rehabilitation. The intended audience for these practice guidelines includes all
      physicians who treat survivors of MI. A literature review of all relevant
      clinical trials and other published data about the natural history after AMI and
      the effects of current therapeutic modalities are discussed herein. Case
      histories served as models for application of the literature-based data. The
      recommendations for management were reached by consensus vote based on the
      scientific evidence. When more than 1 management option applied, this was
      recognized in the recommendations. The recommendations accompany the text.

PMID- 9040294
TI  - Multiple chemical sensitivity syndrome and porphyria. A note of caution and
      concern.
AB  - Growing numbers of patients suffering from many symptoms believe that they have a
      condition called multiple chemical sensitivity syndrome (MCSS). It has been
      suggested that this syndrome can be triggered by exposure to any of a large and
      usually incompletely defined number of natural and synthetic chemical substances.
      Major medical organizations, including the National Research Council and the
      American Medical Association, have not recognized MCSS as a clinical syndrome
      because of a lack of valid, well-controlled studies defining it and establishing
      pathogenesis or origin. Lately, some have proposed that many patients with MCSS
      suffer from hereditary coproporphyria. However, this purported association is
      based chiefly on results from a single reference laboratory of a fundamentally
      flawed assay for erythrocyte coproporphyrinogen oxidase. Although patients with
      MCSS may, at times, have modest increases in urinary coproporphyrin excretion,
      this is a common finding found in many asymptomatic subjects or patients with
      diverse other conditions (eg, diabetes mellitus, heavy alcohol use, liver
      disease, and many kinds of anemia). Such secondary coproporphyrinuria does not
      indicate the existence of coproporphyria. To our knowledge, there is no
      scientifically valid evidence to support an association between MCSS and
      coproporphyria, nor is there any unifying hypothesis for rationally linking these
      2 disorders.

PMID- 9040295
TI  - Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight
      heparin vs intravenous heparin. An economic perspective.
AB  - BACKGROUND: Subcutaneous low-molecular-weight heparin is at least as effective
      and safe as classic intravenous heparin therapy for the treatment of proximal
      vein thrombosis. Anticoagulant monitoring is not required with low-molecular
      weight heparin. OBJECTIVE: To perform an economic evaluation of these therapeutic
      approaches by comparing cost and effectiveness. PATIENTS AND METHODS: A
      randomized trial in 432 patients with proximal vein thrombosis that compared
      intravenous heparin and low-molecular-weight heparin with objective documentation
      of clinical outcomes provided the opportunity to perform an analysis of cost
      effectiveness to rank these alternative therapies in terms of both their cost and
      effectiveness. The economic viewpoint of this analysis was that of a third-party
      payer (ie, a ministry of health in Canada or an insurance company in the United
      States). RESULTS: In the intravenous heparin-treated group, the cost incurred for
      100 patients was $414,655 (Canadian dollars) or $375,836 (US dollars), with a
      frequency of objectively documented venous thromboembolism of 6.9%. In the low
      molecular-weight heparin-treated group, the cost incurred for 100 patients was
      $399,403 (Canadian dollars) or $335,687 (US dollars), with a frequency of
      objectively documented venous thromboembolism of 2.8%, thus providing a cost
      saving of $15,252 (Canadian dollars) or $40,149 (US dollars). Multiple
      sensitivity analyses were performed, and these procedures did not alter the
      findings of the study. CONCLUSIONS: The findings indicate that low-molecular
      weight heparin therapy is at least as effective and safe but less costly than
      intravenous heparin treatment. The potential for outpatient therapy in up to 37%
      of patients who are receiving low-molecular-weight heparin would substantially
      augment the cost saving.

PMID- 9040296
TI  - Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep
      vein thrombosis after hip or knee implantation. An economic perspective.
AB  - BACKGROUND: Postoperative venous thrombosis and pulmonary embolism present a
      major clinical threat to patients undergoing total hip or knee arthroplasty. We
      performed an economic evaluation of warfarin sodium and subcutaneous low
      molecular-weight heparin sodium prophylaxis comparing cost and effectiveness.
      METHODS: A consecutive series of 1436 patients who underwent hip or knee
      arthroplasty comparing these 2 regimens in a randomized trial with objective
      documentation of outcomes provided the opportunity to perform economic
      evaluations for Canada and the United States. RESULTS: Deep vein thrombosis was
      documented in 231 (37.4%) of 617 patients given warfarin and in 185 (31.4%) of
      590 patients given low-molecular-weight heparin (P = .03). In Canada, warfarin
      and low-molecular-weight heparin (tinzaparin sodium) incurred costs per 100
      patients of $11,598 and $9,197, respectively, providing a cost savings of $2,401
      for the low-molecular-weight heparin group. The drug cost of low-molecular-weight
      heparin (tinzaparin) was $6 per day and for warfarin was $0.32 per day.
      Sensitivity analysis showed that low-molecular-weight heparin is more costly if
      drug costs are increased by 1.5-fold (ie, the cost of tinzaparin is increased
      from $6 per day to $8.82 per day or more). In the United States, the analysis was
      also not definitive; low-molecular-weight heparin was more costly than warfarin
      at drug costs of $15 and $2.01 per day, respectively. CONCLUSIONS: Our findings
      indicate that the decision to use low-molecular-weight heparin or warfarin
      prophylaxis in patients undergoing major joint replacement surgery is a finely
      tuned trade-off. Prophylaxis with low-molecular-weight heparin is equally or more
      effective than the more complex prophylaxis with warfarin. Major bleeding is
      uncommon but less frequent with warfarin use. The most significant parameters
      that influence the comparative cost-effectiveness are the cost of the drug, the
      cost of international normalized ratio monitoring, and the costs associated with
      major bleeding. The analysis also demonstrates that the results are health care
      system dependent (Canada vs US). In Canada, low-molecular-weight heparin
      (tinzaparin) is less costly because it avoids the need for international
      normalized ratio monitoring. In the United States, the drug cost for low
      molecular-weight heparin will likely be the principal determinant of relative
      cost-effectiveness.

PMID- 9040297
TI  - Free-floating thrombus and embolic risk in patients with angiographically
      confirmed proximal deep venous thrombosis. A prospective study.
AB  - BACKGROUND: A free-floating thrombus (FFT) is often considered to be a risk
      factor for pulmonary embolism (PE), despite adequate anticoagulation therapy, in
      patients with proximal deep venous thrombosis. METHODS: Ninety-five patients
      underwent prospective assessment according to the presence (FFT group [n = 62])
      or absence (occlusive thrombus group [n = 28]) of an FFT. On day 1, color venous
      duplex scanning, venography (reference method), perfusion lung scanning, and, if
      results of the lung scan were abnormal, pulmonary angiography were performed. On
      day 10 (range, days 9-11), the lung scan was repeated, as well as pulmonary
      angiography if the lung scan demonstrated impairment. A 3-month clinical follow
      up visit was scheduled. Five patients were retrospectively excluded from analysis
      for uncertain diagnosis of FFT. Patients were treated with intravenous
      unfractionated heparin sodium adjusted for activated partial thromboplastin time
      (n = 1) or subcutaneous low-molecular-weight heparin (n = 89) (nadroparin
      calcium, 225 Institut Choay factor Xa inhibitory units per kilogram for 12
      hours). Warfarin sodium therapy was initiated on day 3 (range, days 2-4).
      RESULTS: Both groups were well-matched according to age, sex, risk factors, and
      delay from onset of symptoms to treatment. Positive and negative predictive
      values of color venous duplex scanning for the diagnosis of an FFT were 91% and
      55%, respectively. On admission, PE prevalence was 64% in the FFT group (40 of 62
      patients) and 50% in the occlusive thrombus group (14 of 28 patients) (P = .19).
      Two patients were excluded on follow-up analysis (range, days 9-11) for
      preventive vena cava filtering (due to major bleeding in 1 and cholecystectomy in
      the other); the recurrent rate of PE was 3.3% in the FFT group (2 of 61 patients)
      and 3.7% in the occlusive thrombus group (1 of 27 patients). No symptomatic
      recurrent PE occurred between day 10 (range, days 9-11) and 3 months. Four
      patients died of evolutive neoplasm after hospital discharge. CONCLUSIONS: No
      higher risk for PE was observed in patients with free-floating proximal deep
      venous thrombosis; anticoagulant therapy should prevent recurrent PE in such
      patients.

PMID- 9040298
TI  - Anonymous HIV testing using home collection and telemedicine counseling. A
      multicenter evaluation.
AB  - BACKGROUND: Home human immunodeficiency virus (HIV) testing has been proposed as
      an alternative to conventional HIV testing. Despite debate over HIV type 1 (HIV
      1) home test systems, these concerns have not to our knowledge been previously
      studied. OBJECTIVE: To evaluate the safety and efficacy of the Home Access Health
      Corp (Hoffman Estates, Ill) HIV-1 test system compared with traditional HIV-1
      testing with venous blood. METHODS: A total of 1255 subjects were studied
      prospectively in a blinded, subject-as-control evaluation at 9 outpatient clinics
      using intent-to-treat analysis. Subjects were provided a home collection kit
      (Home Access Health Corp) to collect their own finger-stick blood spot samples
      for laboratory analysis. Subjects received pretest counseling by telephone and
      their comprehension was subsequently assessed. Subject-collected blood spot
      samples were compared with professionally drawn blood spot samples for adequacy
      (sufficient for completing the Food and Drug Administration-endorsed testing) and
      with venous samples for accuracy. Subjects called 3 days later for anonymous
      results and posttest counseling. Device safety was evaluated based on adverse
      events incidence. Subject comprehension of HIV information was measured. RESULTS:
      Subject-collected blood spot sample results were in complete agreement with
      venous blood sample results, demonstrating 100% sensitivity and 100% specificity
      compared with venous controls. Ninety-eight percent of subjects obtained testable
      blood spot specimens compared with phlebotomists. Following pretest counseling,
      subjects answered 96% of HIV risk questions correctly. There were no significant
      adverse events. CONCLUSION: Anonymous HIV-1 home collection kits with pretest and
      posttest telephone counseling can provide a safe and effective alternative to
      conventional venous HIV-1 antibody testing.

PMID- 9040299
TI  - Polymyalgia rheumatica without significantly increased erythrocyte sedimentation
      rate. A more benign syndrome.
AB  - BACKGROUND: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is
      considered an important requisite for the diagnosis of polymyalgia rheumatica
      (PMR). However, the relative frequency and clinical features of PMR in patients
      without a significantly increased ESR are unclear. METHODS: We performed a
      retrospective study of patients diagnosed as having PMR at the rheumatology
      divisions of 3 teaching hospitals. The diagnosis of PMR was established,
      regardless of the ESR, in 201 consecutive patients fulfilling the following
      criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1
      month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3)
      rapid resolution of the syndrome while taking low-dose prednisone. Patients with
      giant cell arteritis were previously excluded from the study. The frequency and
      clinical features of patients with PMR and an ESR lower than 40 mm/h were
      analyzed. A comparative study between these patients and those with high ESRs was
      performed. RESULTS: An ESR lower than 40 mm/h was found in 41 patients (20.4%).
      These patients were younger (P = .02), were more frequently men (P = .006), and
      experienced a lower frequency of fever (P = .003) and weight loss (P = .07).
      Furthermore, these patients were characterized by an absence of anemia (P = .002)
      and a lower frequency of abnormal protein electrophoresis results (P < .001).
      Otherwise, their clinical syndrome, response to therapy, and frequency of
      relapses were similar to those of patients with classic PMR. In the entire
      population of 201 patients, the ESR was related to the length of treatment,
      number of areas involved, presence of fever, weight loss, and laboratory test
      result abnormalities, but it was unrelated to the duration of the illness prior
      to diagnosis. CONCLUSIONS: It is not uncommon to find a patient with PMR with an
      ESR lower than 40 mm/h. This syndrome is more frequent in men and it is
      clinically less severe than the classic form of PMR. Its recognition will allow
      these patients to benefit from an effective treatment with low-dose
      corticosteroids.

PMID- 9040300
TI  - High incidence of pneumonia in elderly patients with basal ganglia infarction.
AB  - BACKGROUND: Pneumonia is a major cause of death in patients with cerebral
      infarction. We assessed morbidity associated with pneumonia in 276 patients 65
      years of age or older who were admitted to a long-term care facility.
      Furthermore, we studied the swallowing reflex during the day and at night and
      monitored the occurrence of silent aspiration during sleep. OBJECTIVES: To
      examine the possible relationship between the location of cerebral hemispheric
      infarctions and the incidence of pneumonia and to evaluate the role of silent
      aspiration in the development of pneumonia. METHODS: The incidence of pneumonia
      was analyzed in 4 groups of patients who were assigned to a group on the basis of
      the following computed tomographic findings: no infarct (group A); 1 or more
      unilateral basal ganglia infarcts (group B); bilateral basal ganglia infarcts
      (group C); and 1 or more cerebral hemispheric infarcts outside the basal ganglia
      (group D). Criteria for diagnosis of pneumonia were (1) a new pulmonary
      infiltrate seen on a chest radiograph and (2) 1 or more of the following
      features: cough, temperature greater than 37.8 degrees C, or subjective dyspnea.
      Before the study, the patients with stroke were followed up for more than 1 year
      after their ictus and were monitored to determine if they sustained affecting
      cerebral hemispheric structures. The average duration of observation for
      incidence of pneumonia was 22 months. To study the swallowing reflex and to
      monitor for the occurrence of silent aspiration during sleep, 15 of the patients
      who were confined to bed or chair were randomly selected from each of groups A
      through C. The swallowing reflex was examined at both 1 PM and 1 AM and was
      evaluated according to latency of response, which was timed from the injection of
      1 mL of distilled water into the pharynx through a nasal catheter to the onset of
      swallowing. The incidence of silent aspiration during sleep was examined using
      indium-111 chloride as a radioactive tracer attached to the teeth, and scanning
      of the thorax was performed the next morning. RESULTS: The incidence of pneumonia
      was 2.12 times higher in the patients of group B (27.4%; P < .01) and 3.64 times
      higher in the patients of group C (47.0%; P < .001) than in the patients of group
      A (12.9%). The latency of response was longer in the patients of groups B (P <
      .05) and C (P < .001) than in those of group A at 1 AM. The percentage of
      positive scans was also higher in the patients of groups B (P < .01) and C (P <
      .001) than in those of group A. CONCLUSION: Basal ganglia strokes might
      predispose these patients to develop pneumonia owing to frequent aspiration
      during sleep.

PMID- 9040301
TI  - The risk factors and impact on survival of feeding tube placement in nursing home
      residents with severe cognitive impairment.
AB  - BACKGROUND: The provision of artificial enteral nutrition to an aged person with
      severe cognitive impairment is a complex dilemma in the long-term care setting.
      OBJECTIVE: To determine the risk factors and impact on survival of feeding tubes
      in nursing home residents with advanced cognitive impairment. METHODS: We
      conducted a cohort study with 24-month follow-up using Minimum Data Set resident
      assessments on 1386 nursing home residents older than 65 years with recent
      progression to severe cognitive impairment in the state of Washington. Residents
      within this population who underwent feeding tube placement were identified.
      Clinical characteristics and survival for a period of 24 months were compared for
      residents who were and were not tube fed. RESULTS: Among the residents with
      recent progression to severe cognitive impairment, 9.7% underwent placement of a
      feeding tube. Factors independently associated with feeding tube placement
      included age younger than 87 years (odds ratio [OR], 1.85; 95% confidence
      interval [CI], 1.25-2.78), aspiration (OR, 5.46; 95% CI, 2.66-11.20), swallowing
      problems (OR, 3.00; 95% CI, 1.81-4.97), pressure ulcer (OR, 1.64; 95% CI, 1.23
      2.95), stroke (OR, 2.12; 95% CI, 1.17-2.62), less baseline functional impairment
      (OR, 2.07; 95% CI, 1.27-3.36), no do-not-resuscitate order (OR, 3.03; 95% CI,
      1.92-4.85), and no dementia (OR, 2.17; 95% CI, 1.43-3.22). Survival did not
      differ between groups of residents with and without feeding tubes even after
      adjusting for independent risk factors for feeding tube placement. CONCLUSIONS:
      There are specific risk factors associated with feeding tube placement in nursing
      home residents with severe cognitive impairment. However, there is no survival
      benefit compared with similar residents who are not tube fed. These prognostic
      data are important for health care providers, families, and patients making
      decisions regarding enteral nutritional support in long-term care.

PMID- 9040302
TI  - Smoking behavior on the first day of a quit attempt predicts long-term
      abstinence.
AB  - BACKGROUND: The nicotine patch has been widely used for smoking cessation, but
      not all smokers quit using the patch. Knowing which smokers are likely to succeed
      with the nicotine patch may improve the efficiency of nicotine patch use.
      OBJECTIVE: To identify predictors of smoking abstinence using baseline
      characteristics, smoking behavior, and withdrawal symptoms. METHODS: Using 2
      randomized clinical trials of pharmacologic treatment, brief counseling, and quit
      date formats in the outpatient research clinic setting, predictors of smoking
      cessation were derived in 1 sample (n = 159), then prospectively validated in an
      independent sample (n = 48). Subjects smoked 1 pack of cigarettes per day or more
      and were motivated to quit smoking. Self-report of abstinence at 6 months
      verified by exhaled carbon monoxide of 8 ppm or less was used. RESULTS:
      Abstinence at 6 months was 24% in the derivation set and 25% in the validation
      set. Using logistic regression, a model containing quit date abstinence (odds
      ratio, 10.6; 95% confidence interval [CI], 2.9-38.7) and baseline nicotine
      dependence (odds ratio, 0.75; 95% CI, 0.6-1.0 per unit increase in Fagerstrom
      score) provided the optimal predictive ability and was validated in the
      independent set. Quit date abstinence improved the likelihood of 6-month
      abstinence by 4.1 over baseline (95% CI, 2.6-6.4) for low-nicotine-dependent
      smokers and 1.2 (95% CI, 0.6-2.2) for high-nicotine-dependent smokers. Quit date
      smoking altered the likelihood of 6-month abstinence by 0.2 (95% CI, 0.0-0.8) for
      low-dependent smokers and 0.1 for high-dependent smokers (95% CI, 0.0-0.6).
      CONCLUSIONS: Abstinence on the quit date and low-nicotine dependence improve the
      likelihood of smoking abstinence at 6 months. Smoking on the quit date may be an
      indication for postponing the cessation attempt or adjusting the therapy for
      smoking cessation.

PMID- 9040303
TI  - Oral famciclovir for suppression of recurrent genital herpes simplex virus
      infection in women. A multicenter, double-blind, placebo-controlled trial.
      Collaborative Famciclovir Genital Herpes Research Group.
AB  - OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the
      suppression of genital herpes. METHODS: In this randomized, double-blind, placebo
      controlled trial that was performed at 11 university and 9 private ambulatory
      care referral centers, 375 women who were 18 years of age or older and had a
      history of 6 or more episodes of genital herpes during 12 of the last 24 months
      in the absence of suppressive therapy were treated for 4 months with oral
      famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily,
      500 mg once daily, or placebo. The primary outcome measures included the time to
      first clinically and virologically confirmed recurrences, and safety as measured
      by clinical laboratory tests and adverse experiences. RESULTS: The median time to
      first recurrence was 82 days in the placebo group, 114 days in those receiving
      famciclovir, 125 mg once daily, and more than 120 days in the other treatment
      groups. When compared with placebo recipients, the time to the first clinical
      recurrence was significantly prolonged in subjects who received famciclovir, 125
      mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03),
      and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95%
      confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there
      was no evidence of emergence of resistance during or after suppressive
      famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for
      4 months is an effective, well-tolerated treatment for the suppression of genital
      herpes in women with frequent recurrences, but single daily doses produced less
      complete suppression of genital herpes.

PMID- 9040304
TI  - Pneumocystis carinii pneumonia masquerading as tuberculosis.
AB  - Recent laboratory studies indicate that genetic diversity exists in human strains
      of Pneumocystis carinii. Structural and functional variability in infecting
      strains could result in differences in host-parasite interactions and the natural
      history of P carinii pneumonia. We report 5 unusual cases in which the clinical
      presentation mimicked tuberculosis. All patients were cared for at a university
      based public hospital clinic in Los Angeles, Calif, during a 2-year period. These
      patients were chronically ill, had lost weight, and each had cavities or cystic
      spaces as the primary radiographic findings. None were receiving aerosol
      pentamidine and only one had a history of smoking. Four patients were initially
      treated for tuberculosis and the fifth for disseminated Mycobacterium avium
      complex. Pneumocystis carinii was the only pathogen identified in each case. The
      unusual clinical presentations delayed the diagnosis of P carinii in all 5 cases.
      Practitioners must be aware of the variable presentations of P carinii pneumonia.

PMID- 9040305
TI  - Methodological studies of systematic reviews: is there publication bias?

PMID- 9040306
TI  - Acute liver injury associated with amoxicillin-clavulanic acid.

PMID- 9040307
TI  - Multiple myeloma in young patients.

PMID- 9040308
TI  - Nutritional counseling in community office practices.

PMID- 9040309
TI  - NSAID gastropathy.

PMID- 9040310
TI  - New guidelines on asthma management.

PMID- 9040311
TI  - Managing measles.

PMID- 9040312
TI  - Reducing vitamin A deficiency.

PMID- 9040313
TI  - Surgery, drugs, and the male orgasm.

PMID- 9040314
TI  - Cardiac sarcoidosis.

PMID- 9040315
TI  - Telling patients they have Alzheimer's disease.

PMID- 9040316
TI  - Routine mammograms not recommended for younger women.

PMID- 9040317
TI  - Drug testing kit approved for sale in US.

PMID- 9040318
TI  - Dutch euthanasia rules relaxed.

PMID- 9040319
TI  - Medicare hospital fees will be frozen.

PMID- 9040320
TI  - Immune response to a new hepatitis B vaccine in healthcare workers who had not
      responded to standard vaccine: randomised double blind dose-response study.
AB  - OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a new triple S
      recombinant hepatitis B vaccine in a cohort of healthy people in whom currently
      licensed hepatitis B vaccines had persistently not induced an immune response.
      DESIGN: Single centre, randomised, double blind, dose-response study. SETTING:
      Research vaccine evaluation centre at a teaching hospital. SUBJECTS: 100
      healthcare workers aged 18-70 years with a history of failure to seroconvert
      after at least four doses of a licensed hepatitis B vaccine containing the S
      component. INTERVENTION: Each subject was randomly allocated two doses of 5, 10,
      20, or 40 micrograms of a new hepatitis B vaccine two months apart. MAIN OUTCOME
      MEASURES: Immunogenicity of the four doses. Seroconversion and seroprotection
      were defined as an antibody tire > 10 IU/l and > 100 IU/l respectively against an
      international antibody standard. RESULTS: 69 subjects seroconverted after a
      single dose of the vaccine. After the booster vaccination one other subject
      seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects
      given 5 micrograms of vaccine, 19 given 10 micrograms, 16 given 20 micrograms,
      and 20 given 40 micrograms seroconverted. Seroconversion rates in the four
      antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25).
      After the booster dose there was no significant dose-response effect on the
      overall seroconversion rate, although the small sample size meant that a
      clinically important dose-response could not be ruled out. CONCLUSION: A single
      dose of 20 micrograms of the vaccine was as effective as two doses of either 40
      micrograms or 20 micrograms of this vaccine formulation in terms of
      seroconversion, seroprotection, and geometric mean titres.

PMID- 9040321
TI  - Meta-analysis of trials of prophylactic antibiotics for children with measles:
      inadequate evidence.
AB  - OBJECTIVE: To assess whether antibiotics should be given to all children with
      measles in communities with a high case fatality rate. DESIGN: Meta-analysis of
      randomised controlled trials that compared routine antibiotic prophylaxis with no
      antibiotic treatment or selective treatment of pneumonia or sepsis. SUBJECTS: Six
      trials of children admitted to hospital with measles: five in Glasgow, London, or
      New York between 1939 and 1954; and one in India in 1967. MAIN OUTCOME MEASURES:
      Incidence of pneumonia or sepsis, and mortality. RESULTS: All but one of the
      trials were unblinded, and randomisation was either not described or was by
      alternate allocation. In four studies, the incidence of pneumonia or sepsis in
      the control group was similar to that in the antibiotic prophylaxis group; in the
      other two studies, the incidence of pneumonia or sepsis was unusually high in the
      control group so these children had a higher complication rate than the
      antibiotic group. Four of the 764 children given antibiotics died compared with
      one of the 637 controls (exact odds ratio 4.0, mid-P corrected 95% confidence
      interval 0.5 to 101.6). CONCLUSION: The quality of the trials reviewed was poor,
      and they provide weak evidence for giving antibiotics to all children with
      measles. Available evidence suggests that, when mortality from measles is high,
      all children with measles should be treated with vitamin A but antibiotics should
      be given only if a child has clinical signs of pneumonia or other evidence of
      sepsis.

PMID- 9040322
TI  - Commentary: summary statistics of poor quality studies must be treated
      cautiously.

PMID- 9040323
TI  - Respiratory morbidity 10 years after the Union Carbide gas leak at Bhopal: a
      cross sectional survey. The International Medical Commission on Bhopal.
AB  - OBJECTIVE: To examine the role of exposure to the 1984 Bhopal gas leak in the
      development of persistent obstructive airways disease. DESIGN: Cross sectional
      survey. SETTING: Bhopal, India. SUBJECTS: Random sample of 454 adults stratified
      by distance of residence from the Union Carbide plant. MAIN OUTCOME MEASURES:
      Self reported respiratory symptoms; indices of lung function measured by simple
      spirometry and adjusted for age, sex, and height according to Indian derived
      regression equations. RESULTS: Respiratory symptoms were significantly more
      common and lung function (percentage predicted forced expiratory volume in one
      second (FEV1), forced vital capacity (FVC), forced expiratory flow between 25%
      and 75% of vital capacity (FEF25-75), and FEV1/FVC ratio) was reduced among those
      reporting exposure to the gas leak. The frequency of symptoms fell as exposure
      decreased (as estimated by distance lived from the plant), and lung function
      measurements displayed similar trends. These findings were not wholly accounted
      for by confounding by smoking or literacy, a measure of socioeconomic status.
      Lung function measurements were consistently lower in those reporting symptoms.
      CONCLUSION: Our results suggest that persistent small airways obstruction among
      survivors of the 1984 disaster may be attributed to gas exposure.

PMID- 9040324
TI  - Commentary: industry can damage your health.

PMID- 9040325
TI  - Commentary: assessing the effects of environmental pollution when people know
      that they have been exposed.

PMID- 9040326
TI  - Follow up policy after treatment for Hodgkin's disease: too many clinic visits
      and routine tests? A review of hospital records.
AB  - OBJECTIVE: To examine the effectiveness of routine clinic review in detecting
      relapse after treatment for Hodgkin's disease. DESIGN: Review of hospital
      records. SETTING: Regional centre for cancer treatment and research. SUBJECTS:
      210 patients with Hodgkin's disease recruited to a chemotherapy trial protocol
      between 1984 and the end of 1990 who had achieved a complete or partial remission
      after treatment. MAIN OUTCOME MEASURES: The number of clinic visits made by
      patients over the period of observation, the number of relapses occurring during
      that time, and the route by which relapse was detected. RESULTS: The 210 patients
      generated 2512 outpatient reviews, and 37 relapses were detected. Thirty relapses
      (81%) were diagnosed in patients who described symptoms, which in 15 cases had
      resulted in an earlier appointment being arranged. In only four cases (11%; 95%
      confidence interval 4% to 25%) was relapse detected as a result of routine
      physical examination on investigation of a patient who did not have symptoms.
      CONCLUSIONS: Relapse of Hodgkin's disease after treatment is usually detected as
      a result of the investigation of symptoms rather than by routine screening of
      asymptomatic patients. It is therefore proposed that the frequency of routine
      follow up visits should be reduced and greater emphasis placed on patient
      education. This should underline the importance of symptoms and encourage
      patients to arrange an earlier appointment if these develop.

PMID- 9040327
TI  - Duplication of surgical research presentations.

PMID- 9040328
TI  - A randomised controlled trial of dictating the clinic letter in front of the
      patient.

PMID- 9040329
TI  - Commentary: interesting idea, but case not proved.

PMID- 9040330
TI  - Acute eosinophilic pneumonia associated with tenidap.

PMID- 9040331
TI  - Potentiation of warfarin anticoagulant activity by miconazole oral gel.

PMID- 9040332
TI  - Duration and recurrence of otitis media with effusion in children from birth to 3
      years: prospective study using monthly otoscopy and tympanometry.
AB  - OBJECTIVE: To monitor the natural course of otitis media with effusion. DESIGN:
      Prospective, longitudinal assessment of the state of the middle ear by otoscopy
      and tympanometry at monthly intervals from birth to 3 years. SETTING: Domiciliary
      visits to family homes. SUBJECTS: 95 full term infants born between August 1991
      and November 1993. MAIN OUTCOME MEASURES: Observed and simulated data (Monte
      Carlo) for the duration of single episodes of otitis media with effusion.
      RESULTS: 17 of the children had unilateral or bilateral otitis media with
      effusion for more than half of their first three years of life. Thirty three of
      the 95 children had tympanograms suggestive of otitis media with effusion at more
      than a third of observations; the remaining 62 had such tympanograms at less than
      a third of observations. The data of each group were described by a first order
      Markov model, yielding a mean duration of unilateral effusion episodes of 5-6
      weeks in both groups; the mean duration of bilateral effusion was 6 and 10 weeks
      in the low and high incidence groups, respectively. However, the main difference
      between the groups was the time spent between episodes of effusion: effusion free
      periods were, on average, three times longer in the children who experienced less
      otitis media with effusion. CONCLUSION: Children who are susceptible to otitis
      media with effusion tend to have more separate episodes of effusion rather than
      an increased overall duration of episodes. Such children are primarily
      distinguished by the likelihood with which they acquire the disease than by their
      ability to recover from it.

PMID- 9040333
TI  - Commentary: reduced confusion over ear effusion?

PMID- 9040334
TI  - Commentary: Markov models of medical prognosis.

PMID- 9040335
TI  - The future of the management of ischaemic heart disease.
AB  - Ischaemic heart disease will kill over 150,000 people in the next year in
      Britain, more than any other single disease process, and cost more than 1.4bn
      pounds in health care alone. Faced with the continuing problems arising from
      ischaemic heart disease cardiological clinician scientists are moving from
      technology based solutions to basic sciences. This article explains how basic
      science may contribute to new understanding and treatments for patients with
      ischaemic heart disease. Highlighted are three problems which face any clinical
      cardiologist on a daily basis and for which basic science may provide solutions:
      the uncertainty of plaque stability in coronary disease; restenosis after
      percutaneous transluminal angioplasty; and the shortage of organs for cardiac
      transplant programmes for patients with heart failure.

PMID- 9040336
TI  - ABC of clinical haematology. Iron deficiency anaemia.

PMID- 9040337
TI  - Cyclosporin treatment for ulcerative colitis complicated by fatal Pneumocystis
      carinii pneumonia.

PMID- 9040338
TI  - Regulating the price of the UK's drugs: second thoughts after the government's
      first report.

PMID- 9040339
TI  - Bed shortages. Regional intensive care unit transfer teams are needed.

PMID- 9040340
TI  - Bed shortages. Hospitals need support for coping with emergency work.

PMID- 9040341
TI  - Delay in diagnosis of homocystinuria. Neonatal screening avoids complications of
      delayed treatment.

PMID- 9040342
TI  - Delay in diagnosis of homocystinuria. Total rather than free homocysteine is
      better for screening.

PMID- 9040343
TI  - Future of the NHS will be one of change.

PMID- 9040344
TI  - Many claims about passive smoking are inadequately justified.

PMID- 9040345
TI  - Congenital anterior abdominal wall defects. A national congenital malformations
      register is needed.

PMID- 9040346
TI  - Congenital anterior abdominal wall defects. Rate of abdominal wall defects is
      higher in Scotland than England and Wales.

PMID- 9040347
TI  - Congenital anterior abdominal wall defects. Authors' figures for Northern region
      are underestimates.

PMID- 9040348
TI  - Congenital anterior abdominal wall defects. Gastroschisis has a good prognosis.

PMID- 9040349
TI  - Giving influenza vaccination to all elderly people would raise ethical issues.

PMID- 9040350
TI  - Helping parents to cope when their preschool children are acutely ill.
      Educational interventions may defuse parents' concern.

PMID- 9040351
TI  - Helping parents to cope when their preschool children are acutely ill. Patients
      and GPs need to understand each other's perceptions of a consultation.

PMID- 9040352
TI  - Many trusts find labour productivity index useful.

PMID- 9040353
TI  - The Babinski sign. Eliciting the sign brings out doctors' masochistic tendencies.

PMID- 9040354
TI  - The Babinski sign. Reliability of new technology must be alarmingly low.

PMID- 9040355
TI  - Associate specialists are included in colleges' scheme for continuing medical
      education.

PMID- 9040356
TI  - Inquiry into homicides by psychiatric patients. Why inquiries are necessary.

PMID- 9040357
TI  - Inquiry into homicides by psychiatric patients. Confidential inquiry is best.

PMID- 9040358
TI  - Stabilisation of the population is necessary for health for all.

PMID- 9040359
TI  - Telling the diagnosis to patients with Alzheimer's disease. Relatives should act
      as proxy for patient.

PMID- 9040360
TI  - Telling the diagnosis to patients with Alzheimer's disease. Geriatricians' and
      psychiatrists' practice differs.

PMID- 9040361
TI  - 20% of patients may refuse consent to disclosure of information for Benefits
      Agency.

PMID- 9040362
TI  - Study about prehospital emergency care was cited incorrectly.

PMID- 9040363
TI  - Women need to be warned about dangers of hormone replacement therapy.

PMID- 9040364
TI  - Effect of psychogeriatric team on depression in frail elderly people at home.
      More information is needed on subjects and interventions in study.

PMID- 9040366
TI  - A very public death.

PMID- 9040365
TI  - Effect of psychogeriatric team on depression in frail elderly people at home.
      Results may have been due to intervention by a specialist.

PMID- 9040367
TI  - Ethical issues in genetics ignored.

PMID- 9040368
TI  - Dietary selenium: time to act.

PMID- 9040369
TI  - Introducing the postoperative care team.

PMID- 9040370
TI  - Erasing the global divide in health research.

PMID- 9040371
TI  - Epilepsy: a progressive disease?

PMID- 9040372
TI  - Children in cars.

PMID- 9040373
TI  - Doctors complain about treatment of asylum seekers in Britain.

PMID- 9040374
TI  - Shackling of prisoners denounced.

PMID- 9040375
TI  - Changes to mental health care proposed.

PMID- 9040376
TI  - Government proposes food safety adviser.

PMID- 9040377
TI  - South African court rules against rationing decision.

PMID- 9040378
TI  - US recommends screening for colon cancer.

PMID- 9040379
TI  - Sickle cell disease is poorly managed.

PMID- 9040380
TI  - Italians ban Hib vaccine in BSE scare.

PMID- 9040381
TI  - Care of Dutch mentally ill prisoners criticised.

PMID- 9040382
TI  - France plans compulsory treatment of sex offenders.

PMID- 9040383
TI  - US doctors urged to treat stroke fast.

PMID- 9040384
TI  - Clinical course of untreated tonic-clonic seizures in childhood: prospective,
      hospital based study.
AB  - OBJECTIVE: To assess decleration and acceleration in the disease process in the
      initial phase of epilepsy in children with new onset tonic-clonic seizures. STUDY
      DESIGN: Hospital based follow up study. SETTING: Two university hospitals, a
      general hospital, and a children's hospital in the Netherlands. PATIENTS: 204
      children aged 1 month to 16 years with idiopathic or remote symptomatic, newly
      diagnosed, tonic-clonic seizures, of whom 123 were enrolled at time of their
      first ever seizure; all children were followed until the start of drug treatment
      (78 children), the occurrence of the fourth untreated seizure (41 children), or
      the end of the follow up period of two years (85 untreated children). MAIN
      OUTCOME MEASURES: Analysis of disease pattern from first ever seizure. The
      pattern was categorised as decelerating if the child became free of seizures
      despite treatment being withheld. In cases with four seizures, the pattern was
      categorised as decelerating if successive intervals increased or as accelerating
      if intervals decreased. Patterns in the remaining children were classified as
      uncertain. RESULTS: A decelerating pattern was found in 83 of 85 children who
      became free of seizures without treatment. Three of the 41 children with four or
      more untreated seizures showed a decelerating pattern and eight an accelerating
      pattern. In 110 children the disease process could not be classified, mostly
      because drug treatment was started after the first, second, or third seizure. The
      proportion of children with a decelerating pattern (42%, 95% confidence interval
      35% to 49%) may be a minimum estimate because of the large number of patients
      with an uncertain disease pattern. CONCLUSIONS: Though untreated epilepsy is
      commonly considered to be a progressive disorder with decreasing intervals
      between seizures, a large proportion of children with newly diagnosed, unprovoked
      tonic-clonic seizures have a decelerating disease process. The fear that tonic
      clonic seizures commonly evolve into a progressive disease should not be used as
      an argument in favour of early drug treatment in children with epilepsy.

PMID- 9040385
TI  - Neonatal risk factors for cerebral palsy in very preterm babies: case-control
      study.
AB  - OBJECTIVE: To identify neonatal risk factors for cerebral palsy among very
      preterm babies and in particular the associations independent of the coexistence
      of antenatal and intrapartum factors. DESIGN: Case-control study. SETTING: Oxford
      health region. SUBJECTS: Singleton babies born between 1984 and 1990 at less than
      32 weeks' gestation who survived to discharge from hospital: 59 with cerebral
      palsy and 234 randomly selected controls without cerebral palsy. MAIN OUTCOME
      MEASURES: Adverse neonatal factors expressed as odds ratios and 95% confidence
      intervals. RESULTS: Factors associated with an increased risk of cerebral palsy
      after adjustment for gestational age and the presence of previously identified
      antenatal and intrapartum risk factors were patent ductus arteriosus (odds ratio
      2.3; 95% confidence interval 1.2 to 4.5), hypotension (2.3; 1.3 to 4.7), blood
      transfusion (4.8; 2.5 to 9.3), prolonged ventilation (4.8; 2.5 to 9.0),
      pneumothorax (3.5; 1.6 to 7.6), sepsis (3.6; 1.8 to 7.4), hyponatraemia (7.9; 2.1
      to 29.6) and total parenteral nutrition (5.5; 2.8 to 10.5). Seizures were
      associated with an increased risk of cerebral palsy (10.0; 4.1 to 24.7), as were
      parenchymal damage (32; 12.4 to 84.4) and appreciable ventricular dilatation
      (5.4; 3.0 to 9.8) detected by cerebral ultrasound. CONCLUSION: A reduction in the
      rate of cerebral palsy in very preterm babies requires an integrated approach to
      management throughout the antenatal, intrapartum, and neonatal periods.

PMID- 9040386
TI  - Survival after diagnosis of AIDS: a prospective observational study of 2625
      patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.
AB  - OBJECTIVE: To estimate median survival and changes in survival in patients
      diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING:
      Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen
      between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using
      lifetable analyses, and factors associated with survival, identified from Cox
      proportional hazards models. RESULTS: Median survival (20 months) was longer than
      previous estimates. The CD4 lymphocyte count at or before initial AIDS defining
      illness decreased significantly over time from 90 x 10(6)/1 during 1987 or
      earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three
      months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much
      lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P
      = 0.017) than patients diagnosed before 1987. When the diagnosis was based on
      oesophageal candidiasis or Kaposi's sarcoma, patients had a lower risk of death
      than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07
      to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS
      diagnosis, the risk of death was similar in patients whose diagnosis was made
      after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences
      in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5.
      CONCLUSIONS: In later years, patients were much more likely to survive their
      initial illness, but long term survival has remained poor. The decrease in CD4
      lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as
      having AIDS at ever more advanced stages of immunodeficiency.

PMID- 9040387
TI  - Young people, alcohol, and designer drinks: quantitative and qualitative study.
AB  - OBJECTIVE: To examine the appeal of "designer drinks" to young people. DESIGN:
      Qualitative and quantitative research comprising group discussions and
      questionnaire led interviews with young people accompanied by a self completion
      questionnaire. SETTINGS: Argyll and Clyde Health Board area, west Scotland.
      SUBJECTS: Eight groups aged 12-17 years; 824 aged 12-17 recruited by multistage
      cluster probability sample from the community health index. RESULTS: Young people
      were familiar with designer drinks, especially MD 20/20 and leading brands of
      strong white cider. Attitudes towards these drinks varied quite distinctly with
      age, clearly reflecting their attitudes towards and motivations for drinking in
      general. The brand imagery of designer drinks-in contrast with that of more
      mainstream drinks-matched many 14 and 15 year olds' perceptions and expectations
      of drinking. Popularity of designer drinks peaked between the ages of 13 and 16
      while more conventional drinks showed a consistent increase in popularity with
      age. Consumption of designer drinks tended to be in less controlled circumstances
      and was associated with heavier alcohol intake and greater drunkenness.
      CONCLUSIONS: Designer drinks are a cause for concern. They appeal to young
      people, often more so than conventional drinks, and are particularly attractive
      to 14-16 year olds. Consumption of designer drinks is also associated with
      drinking in less controlled environments, heavier drinking, and greater
      drunkenness. There is a need for policy debate to assess the desirability of
      these drinks and the extent to which further controls on their marketing are
      required.

PMID- 9040388
TI  - Impotence after sclerotherapy of haemorrhoids: case reports.

PMID- 9040389
TI  - Efficacy of the alcohol use disorders identification test as a screening tool for
      hazardous alcohol intake and related disorders in primary care: a validity study.
AB  - OBJECTIVE: To determine the properties of the alcohol use disorders
      identification test in screening primary care attenders for alcohol problems.
      DESIGN: A validity study among consecutive primary care attenders aged 18-65
      years. Every third subject completed the alcohol use disorders identification
      test (a 10 item self report questionnaire on alcohol intake and related problems)
      and was interviewed by an investigator with the composite international
      diagnostic interview alcohol use module (a standardised interview for the
      independent assessment of alcohol intake and related disorders). SETTING: 10
      primary care clinics in Verona, north eastern Italy. PATIENTS: 500 subjects were
      approached and 482 (96.4%) completed evaluation. RESULTS: When the alcohol use
      disorders identification test was used to detect subjects with alcohol problems
      the area under the receiver operating characteristic curve was 0.95. The cut off
      score of 5 was associated with a sensitivity of 0.84, a specificity of 0.90, and
      a positive predictive value of 0.60. The screening ability of the total score
      derived from summing the responses to the five items minimising the probability
      of misclassification between subjects with and without alcohol problems provided
      an area under the receiver operating characteristic curve of 0.93. A score of 5
      or more on the five items was associated with a sensitivity of 0.79, a
      specificity of 0.95, and a positive predictive value of 0.73. CONCLUSIONS: The
      alcohol use disorders identification test performs well in detecting subjects
      with formal alcohol disorders and those with hazardous alcohol intake. Using five
      of the 10 items on the questionnaire gives reasonable accuracy, and these are
      recommended as questions of choice to screen patients for alcohol problems.

PMID- 9040390
TI  - The diagnosis of pulmonary embolism.
AB  - Currently, clinicians have to make decisions about how to manage pulmonary
      embolism on the basis of imperfect tests and assessment of odds. Management
      protocols that inevitably result in large numbers of patients being referred for
      angiography are unhelpful. Management decisions based on assessment of odds and
      investigation of leg veins will inevitably result in some patients who have
      survived a pulmonary embolus being left untreated. Current evidence suggests that
      for most patients this is probably not important, the clear exception being those
      patients with underlying cardiorespiratory disease.

PMID- 9040391
TI  - ABC of clinical haematology. Macrocytic anaemias.

PMID- 9040392
TI  - Microbial keratitis in intensive care.

PMID- 9040393
TI  - Personal paper: the scapegoating of a consultant orthopaedic surgeon.

PMID- 9040394
TI  - Primary care: opportunities and threats. What the changes mean.

PMID- 9040395
TI  - The BMJ's Nuremberg issue. Many people are still uncomfortable with the topic of
      Nazi medicine.

PMID- 9040396
TI  - The BMJ's Nuremberg issue. Abortion and euthanasia evoke thoughts of Nazi
      Germany.

PMID- 9040397
TI  - The BMJ's Nuremberg issue. College oath requires physicians to do everything for
      the welfare of the state.

PMID- 9040398
TI  - The BMJ's Nuremberg issue. Photographs exploited their subjects.

PMID- 9040399
TI  - The BMJ's Nuremberg issue. Nobody died during experiments on vitamin C and
      vitamin A intakes in Sheffield.

PMID- 9040400
TI  - The BMJ's Nuremberg issue. Compulsory sterilisation of defective people was legal
      in several countries besides Germany.

PMID- 9040401
TI  - The BMJ's Nuremberg issue. Use of Nazi material during medical training left an
      uncomfortable feeling.

PMID- 9040402
TI  - The BMJ's Nuremberg issue. Is enough enough?

PMID- 9040403
TI  - Access to computed tomography in British accident and emergency departments.

PMID- 9040404
TI  - Who should talk to patients with cancer about genetics?

PMID- 9040405
TI  - Registering a fetus papyraceus. Registration is important for research into
      cerebral palsy.

PMID- 9040406
TI  - Registering a fetus papyraceus. Health professionals can exercise discretion.

PMID- 9040407
TI  - Purchasers should require providers to set standards for pain relief.

PMID- 9040408
TI  - Diagnosing death. Start resuscitation first.

PMID- 9040409
TI  - Diagnosing death. Death after electric shock and lightning strike is more clear
      cut than suggested.

PMID- 9040410
TI  - Diagnosing death. Death of the brain stem means death of the individual.

PMID- 9040411
TI  - Moderate alcohol consumption has been shown previously to improve insulin
      sensitivity in men.

PMID- 9040412
TI  - CS gas has been used as chemical restraint in mentally ill person.

PMID- 9040413
TI  - Paramedic skills. Data collected on paramedic care need national standardisation.

PMID- 9040414
TI  - Paramedic skills. Two tier system of advanced life support and basic life support
      ambulances is needed.

PMID- 9040415
TI  - Meta-analysis of risk of gastrointestinal complications with NSAIDs. Authors
      should not have included data from one study.

PMID- 9040416
TI  - Meta-analysis of risk of gastrointestinal complications with NSAIDs. Narrative
      review should have been used.

PMID- 9040418
TI  - What is palliative care?

PMID- 9040419
TI  - Palliative care and the suffering index.

PMID- 9040417
TI  - Self administered tampons can be used to diagnose sexually transmitted diseases.

PMID- 9040420
TI  - Pulmonary edema with wide-complex tachycardia.

PMID- 9040421
TI  - Fever and anorexia 10 years after major trauma.

PMID- 9040422
TI  - The genetics of aging.
AB  - There is no aging program, nor is there an aging gene. Instead, we age because
      evolution has no reason to protect us against unwelcome actions of multiple genes
      late in life. Still, every discovery of a harmful mutation or polymorphism raises
      at least the theoretical possibility of other, beneficial alleles- and offers
      clues for understanding the biomolecular mechanisms that underlie senescence.

PMID- 9040423
TI  - Forestalling fracture in osteoporosis.
AB  - When osteoporosis is imminent, simple clinical measures--risk reduction and
      preventive steps such as calcium supplementation and exercise--are in order.
      Estrogen replacement offers excellent protection in menopausal women. When
      disease is apparent, bone densitometry can confirm the diagnosis and therapy can
      be chosen from a widening palette that includes calcitonin and the
      bisphosphonates.

PMID- 9040424
TI  - Keys to managing systemic lupus erythematosus.
AB  - The keys to coping with the variability seen in SLE are accurate differentiation
      of active disease from past damage and consistent monitoring for new disease
      manifestations and medication side effects. Common clinical problems are
      reviewed.

PMID- 9040425
TI  - Prevention of diabetic nephropathy.
AB  - Normalization of blood pressure--and use of an ACE inhibitor or AT1-receptor
      blocker for patients with abnormal albumin or creatinine levels--can prevent or
      significantly slow the rate of progression toward end-stage renal disease.

PMID- 9040426
TI  - The case for aggressive lipid regulation.
AB  - Lowering cholesterol levels with dietary or drug interventions lowers the risk
      for coronary heart disease (CHD) proportionately and reduced CHD morbidity and
      mortality, as well as overall mortality in patients with CHD. Antihyperlipidemic
      drugs are currently underused. Aggressive therapy is warranted for patients with
      established CHD. whose LDL cholesterol levels should be reduced to 100 mg/dL or
      lower.

PMID- 9040427
TI  - Therapeutic approaches to osteoarthritis.
AB  - Management is multifaceted: Palliation of pain should be accompanied by physical
      and occupational therapy and use of adaptive devices to improve performance. New
      techniques aim to interrupt disease progression and to induce biologic repair.

PMID- 9040428
TI  - Acute complications of cocaine intoxication.
AB  - The advent of crack cocaine has changed the face of acute cocaine intoxication.
      Repeated doses of highly concentrated, rapidly delivered drug can give rise to an
      array of potentially fatal cardiovascular, neurologic, and respiratory
      complications.

PMID- 9040429
TI  - Case in point. Hemorrhagic Pancreatitis.

PMID- 9040430
TI  - Impact of managed care on medical students.

PMID- 9040431
TI  - Rosacea: beyond first blush.

PMID- 9040432
TI  - Exercise intolerance and ankle edema in a young woman.

PMID- 9040433
TI  - An unusual case of testicular pain.

PMID- 9040434
TI  - Blood pressure lowering for the secondary prevention of myocardial infarction and
      stroke.

PMID- 9040435
TI  - High prevalence of concentric remodeling in elderly individuals with isolated
      systolic hypertension from a population survey.
AB  - Echocardiographic determination of left ventricular mass index (LVMI) is shown to
      be valuable in the assessment of cardiovascular risk. Determination of left
      ventricular geometry, including concentric remodeling, provides additional
      prognostic information. In isolated systolic hypertension (ISH), the few
      echocardiographic studies available show an increased LVMI, but criteria and
      patient populations differ. No comparison with diastolic hypertension (DH) has
      been made, nor has left ventricular geometry (with concentric remodeling) been
      evaluated. We compared both LVMI and left ventricular geometry of newly diagnosed
      ISH subjects with normotensive and DH subjects, all previously untreated and from
      the same population. The echocardiographic LVMI of 97 previously untreated ISH
      subjects (4 x systolic pressure > or = 160 mm Hg, diastolic pressure < 95 mm Hg)
      was clearly elevated compared with values in age- and sex-matched normotensive
      subjects (98 and 71 g/m2, respectively; P < .001). The geometric pattern was
      abnormal in most ISH subjects, with a high prevalence (43%) of concentric
      remodeling. Both LVMI and left ventricular geometry of ISH subjects did not
      differ significantly from values in DH subjects (LVMI, 92 g/m2; concentric
      remodeling, 56%). Sex differences in LV geometry in ISH were present only with
      the Framingham criteria, not with the Koren criteria. This study shows a high
      prevalence of concentric remodeling in elderly individuals with previously
      untreated ISH. The increase of LVMI and abnormality in left ventricular geometry
      are comparable with those in DH subjects, further defining the place of ISH as a
      cardiovascular risk factor in the elderly. Whether there are sex differences in
      cardiac adaptation in ISH and whether the geometric classification can be used to
      adjust treatment remain to be investigated.

PMID- 9040436
TI  - Left ventricular filling in arterial hypertension. Influence of obesity and
      hemodynamic and structural confounders.
AB  - We assessed the relations of left ventricular filling to load and geometry by
      Doppler echocardiography in 80 normotensive subjects (40 normal-weight [36 +/- 12
      years, 24 women] and 40 obese [35 +/- 13 years, 24 women]) and 61 hypertensive
      subjects without silent coronary heart disease (29 normal-weight [43 +/- 13
      years, 15 women] and 32 obese [42 +/- 13 years, 19 women]) and comparable left
      ventricular midwall performance. Left ventricular mass divided by height to the
      2.7 power was higher in all groups than in normotensive normal-weight subjects
      (all P < .0001) and in hypertensive than normotensive obese subjects (P < .001).
      After controlling for age, sex, blood pressure, and heart rate, isovolumic
      relaxation time was prolonged in hypertensive subjects and normotensive obese
      subjects compared with normotensive normal-weight subjects (all P < .0001). Body
      mass index, left ventricular dimension and mass, and circumferential end-systolic
      stress did not influence these differences. In pooled groups, prolonged
      isovolumic relaxation time was predicted by high mean blood pressure (beta =
      0.52, P < .001), low end-systolic stress (beta = -0.33, P < .001), increased left
      ventricular mass (beta = 0.24, P < .004), and high body mass index (beta = 0.14,
      P < .05, multiple R = .72, SEE = 16.5 milliseconds, P < .0001). Between-group
      differences in peak early transmitral flow velocity, the deceleration time of
      early filling velocity, and the ratio of early to late left ventricular filling
      disappeared after controlling for left ventricular mass. Thus, (1) isovolumic
      relaxation time is prolonged in both arterial hypertension and obesity; (2) the
      presence of obesity does not significantly increase isovolumic relaxation time in
      hypertension; and (3) abnormalities of left ventricular filling in arterial
      hypertension are offset after controlling for left ventricular mass.

PMID- 9040437
TI  - Mechanisms of coronary flow reserve impairment in human hypertension. An
      integrated approach by transthoracic and transesophageal echocardiography.
AB  - The purpose of this study was to investigate the different mechanisms responsible
      for an impairment of coronary vasodilator capacity in hypertensive subjects by an
      integrated echocardiographic approach, including transesophageal Doppler
      echocardiography, which allows noninvasive monitoring of coronary flow velocity
      in the left anterior descending artery during pharmacological vasodilation. The
      study population consisted of 17 healthy control subjects and 33 hypertensive
      subjects: 10 without hypertrophy, 16 with mild to moderate hypertrophy, and 7
      with severe left ventricular hypertrophy. Mean systolic and diastolic flow
      velocities were monitored basally (together with indexes of myocardial oxygen
      demand, such as heart rate, myocardial inotropism, and left ventricular wall
      stress) and during infusion of low-dose (0.56 mg/kg per 4 minutes) and high-dose
      (0.84 mg/kg per 9 minutes) dipyridamole. Coronary reserve was assessed as the
      ratio of mean diastolic velocity after high-dose dipyridamole and basal diastolic
      velocity, and minimum coronary resistance as the ratio of diastolic blood
      pressure and diastolic velocity after high-dose dipyridamole. Compared with the
      control group, in all hypertensive groups, coronary reserve was similarly
      decreased (3.54 +/- 0.84 versus 2.59 +/- 0.42, 2.29 +/- 0.46, and 2.43 +/- 0.71;
      P < .01) and minimum resistance increased (0.56 +/- 0.15 versus 0.75 +/- 0.31,
      0.75 +/- 0.19, and 0.78 +/- 0.21 mm Hg.s-1.cm-1; P = NS). These results confirm
      that coronary reserve in hypertensive individuals is reduced even before the
      occurrence of left ventricular hypertrophy. The reduction in coronary reserve
      depends on both an increase in resting coronary flow and an impairment in maximal
      vasodilator capacity. An increase in resting flow is dependent on higher heart
      rate and wall stress in hypertensive subjects without ventricular hypertrophy and
      on increased myocardial mass in hypertensive subjects with hypertrophy.
      Hypertensive subjects with ventricular hypertrophy also demonstrated a
      significantly blunted response to low-dose dipyridamole.

PMID- 9040438
TI  - Limited echocardiography for hypertensive left ventricular hypertrophy.

PMID- 9040439
TI  - Angiotensin II blockade [corrected] enhances baroreflex control of sympathetic
      outflow in heart failure.
AB  - Enhanced sympathetic outflow is seen in both patients with congestive heart
      failure and animals with experimental heart failure. In a previous study, we
      demonstrated that the baroreflex control of heart rate was impaired in conscious
      rabbits with pacing-induced heart failure and that this impairment was partially
      restored by blockade of angiotensin II type 1 (AT1) receptors. In the present
      study, we determined the interaction between the renin-angiotensin system and
      baroreflex control of renal sympathetic nerve activity in normal conscious
      rabbits and conscious rabbits with pacing-induced heart failure before and after
      AT1 receptor blockade. Heart failure was induced by rapid ventricular pacing at a
      rate of 360 to 380 beats per minute for an average of 16.7 +/- 0.6 days. To
      generate baroreflex curves, we altered arterial pressure by administering
      phenylephrine and sodium nitroprusside. A sigmoidal logistic function was fit to
      renal sympathetic nerve activity-mean arterial pressure relationships for
      analysis of several components of baroreflex function. AT1 receptors were blocked
      by intravenous administration of the specific antagonist L-158,809. In normal
      rabbits, there was no significant difference in any parameter of baroreflex
      function before and after blockade of AT1 receptors. In contrast, blockade of AT1
      receptors enhanced baroreflex sensitivity in heart failure rabbits. The maximal
      gain increased to 5.0 +/- 0.7% renal sympathetic nerve activity/mm Hg from 2.6 +/
      0.3 (P < .05). Although L-158,809 had no effect on baseline renal sympathetic
      nerve activity in normal rabbits, analysis of the data in the heart failure
      rabbits indicated that baseline renal sympathetic nerve activity was reduced from
      33 +/- 5% to 17 +/- 4% after L-158,809 administration after adjustment for
      changes in arterial pressure. These data suggest that angiotensin II plays a role
      in baroreflex impairment in this model of heart failure and may be in part
      responsible for the depressed baroreflex sensitivity observed in heart failure.

PMID- 9040440
TI  - Cyclosporin A increases nitric oxide activity in vivo.
AB  - The use of cyclosporine is complicated by its vaso-constrictive actions. In vitro
      cyclosporine has been associated with both decreased endothelium-dependent
      vasodilatation and increased nitric oxide activity. We studied the interaction
      between cyclosporine and endothelium-derived nitric oxide in seven healthy
      volunteers. Using venous-occlusion plethysmography, we measured forearm blood
      flow during intra-arterial infusion of serotonin, which in the concentrations
      used is a selective agonist of endothelial nitric oxide release, or NG-monomethyl
      L-arginine, a specific inhibitor of nitric oxide synthase, during coinfusion of
      saline or cyclosporine (75 micrograms/min), respectively. During coinfusion of
      cyclosporine, forearm blood flow increased on maximal serotonin infusion from 2.9
      (SE, 0.2) to 8.1 (0.9) mL/100 mL per minute in forearm tissue, which was
      significantly higher than the increase during saline coinfusion (3.0[0.3] to 6.0
      [0.5]; P < .05). Cyclosporine infusion during a "free" nitric oxide system had no
      effect on basal forearm blood flow, but in significantly decreased forearm blood
      flow (21.7[2.8]%; P < .05) during fixed nitric oxide activity. These data suggest
      that acute administration of cyclosporine enhances both basal and receptor
      stimulated nitric oxide activity. The mechanism is not clear but may include
      cyclosporine-induced shear stress as well as direct effects of cyclosporine. The
      latter was supported by our observation that gene expression of the enzyme nitric
      oxide synthase III was enhanced by approximately 50% after coincubation with
      cyclosporine. In conclusion, the present observation demonstrates that nitric
      oxide constitutes an important regulating mechanism that protects against
      cyclosporine-associated vasoconstriction in vivo.

PMID- 9040441
TI  - Sympathoexcitatory response to cyclosporin A and baroreflex resetting.
AB  - We postulate that the sympathoexcitatory response associated with the
      immunosuppressive agent cyclosporin A is due to an upward resetting of the
      arterial baroreflex. We performed studies in conscious intact and sinoaortic
      denervated rabbits instrumented with catheters and renal nerve electrodes. In
      intact rabbits, cyclosporin A (20 mg/kg i.v., 30 minutes) produced significant
      increases in renal sympathetic nerve activity (100% to 269 +/- 74%, P < .05) but
      did not increase mean arterial pressure. In intact rabbits, we determined
      arterial baroreflex curves relating renal sympathetic nerve activity and heart
      rate to mean arterial pressure by producing ramp increases (intravenous
      phenylephrine) and decreases (intravenous nitroprusside) in mean arterial
      pressure. Cyclosporin A treatment produced a shift of the midrange of the
      baroreflex control of heart rate (78.0 +/- 4.1 to 84.6 +/- 4.7 mm Hg, P < .05)
      and renal sympathetic nerve activity (74.6 +/- 3.9 to 87.0 +/- 4.8 mm Hg, P <
      .05). Vehicle administration produced no effects on arterial baroreflex curves
      relating renal sympathetic nerve activity and heart rate to mean arterial
      pressure. Compared with vehicle treatment, cyclosporin A reduced the maximum gain
      of heart rate (-5.6 +/- 0.6 versus -3.1 +/- 0.8 beats per minute per millimeter
      of mercury, P < .05) but had no effect on the maximum gain of renal sympathetic
      nerve activity. In conscious sinoaortic-denervated rabbits, cyclosporin A had no
      effect on mean arterial pressure (95.7 +/- 7.3 to 91.8 +/- 10.8 mm Hg), renal
      sympathetic nerve activity (100% to 110 +/- 6%). and heart rate (287 +/- 10 to
      279 +/- 8 beats per minute). However, when the same sinoaortic-denervated rabbits
      were anesthetized with sodium pentobarbital, cyclosporin A (20 mg/kg i.v.)
      produced increases in renal sympathetic nerve activity (100% to 189 +/- 27%).
      These data indicate (1) that the sympathoexcitatory response to cyclosporin A
      depends on baroreceptor afferent input in the conscious state and (2) that this
      response involves an upward resetting of the arterial baroreflex.

PMID- 9040442
TI  - Combined effects of hypertension and hypercholesterolemia on radial artery
      function.
AB  - Compliance and distensibility of middle-sized conduit arteries are increased in
      hypertension and reduced in hypercholesterolemia. Despite their frequent
      association in the same individual, the combined effect of these two conditions
      on arterial mechanical properties is unknown. We studied four groups of age- and
      sex-matched subjects: 10 normotensive normocholesterolemic subjects, 10 mild
      hypertensive normocholesterolemic subjects, 10 mild hypercholesterolemic
      normotensive subjects, and 10 mild hypertensive and mild hypercholesterolemic
      subjects. We measured radial artery diameter by an echotracking device and beat
      to-beat blood pressure from an ipsilateral finger. Compliance-pressure and
      distensibility-pressure curves were derived by Langewouters' formula. Between
      group comparisons were made by calculating for both compliance and distensibility
      the integral of the area under the portion of the curve common to the four groups
      ("isobaric" compliance and distensibility). Blood pressure was similarly elevated
      in the two hypertensive groups, and serum cholesterol was similarly elevated in
      the two hypercholesterolemic groups. Compared with values in normotensive
      normocholesterolemic subjects, isobaric compliance and distensibility were
      greater in hypertensive normocholesteroclemic (+38% and 47%, respectively) and
      smaller in normotensive hypercholesterolemic (-6% and -23%) subjects. However,
      when both hypertension and hypercholesterolemia were present, isobaric compliance
      and isobaric distensibility were significantly reduced (-26% and -18%, P < .05).
      Therefore, hypercholesterolemia reverses the effect of hypertension on arterial
      compliance and causes arterial stiffening, as when present alone.

PMID- 9040443
TI  - Increased Na(+)-H+ exchange in red blood cells of patients with primary
      aldosteronism.
AB  - We measured Na(+)-H+ exchange as the amiloride-inhibited fraction of H+ efflux
      from red blood cells into a sodium-containing medium (pHo 7.95 to 8.05) at pHi
      values of 6.05 to 6.15, 6.35 to 6.45, 6.95 to 7.05, and 7.35 to 7.45 in 12 drug
      free patients with primary aldosteronism before and after excision of
      histologically proven aldosterone-producing adrenal adenoma, 12 drug-free
      essential hypertensive patients, and 12 healthy control subjects. Red blood cell
      Na(+)-H+ exchange was increased in patients with primary aldosteronism similarly
      to the mean exchanger velocity in essential hypertensive patients compared with
      values in healthy subjects (334 +/- 25 and 310 +/- 29 versus 139 +/- 21 mumol
      H+/L cells per minute, respectively; P < .001 and .01). The kinetic parameters of
      Na(+)-H+ exchange returned to normal on day 2 after removal of the aldosterone
      producing mass. Km for [Na+]o was not affected by aldosterone, whereas Km for
      [H+]i was decreased in patients with primary aldosteronism. The kinetic
      characteristics did not differ in essential hypertensive patients and control
      subjects. Protein kinase C inhibition in vitro by calphostin C (60 nmol/L)
      increased Km for [H+]i and caused up to a 65% suppression of Na(+)-H+ exchange
      (pHi 6.05 to 6.15). while diminishing Km for [Na+]o in red blood cells of
      patients with primary aldosteronism. The calmodulin antagonist W-13 (60 mmol/L)
      decreased exchanger velocity and increased Km for both H+ and Na+. We conclude
      that aldosterone stimulates red blood cell Na(+)-H+ exchange by a nongenomic
      mechanism that augments the exchanger affinity to Na+ and H+. In primary
      aldosteronism, protein kinase C and calmodulin seem to have synergistic
      stimulatory effects on red blood cell Na(+)-H+ exchange, and both increase the
      affinity of the exchanger to H+, while their effect on Na+ binding is opposite.

PMID- 9040444
TI  - Increased brain transcription factor expression by angiotensin in genetic
      hypertension.
AB  - A stimulated brain renin-angiotensin system has been implicated in genetic
      hypertension. We compared the effects of an intracerebroventricular injection of
      angiotensin II (100 ng) on the expression of inducible transcription factors c
      Fos, c-Jun, and Krox-24 in the brain of spontaneously hypertensive rats (SHR). in
      Wistar rats with nephrogenic hypertension induced by aortic banding, and in
      normotensive Wistar-Kyoto and Wistar rats immunohistochemically. Generally, the
      angiotensin II-induced transcription factor expression was strictly confined to
      four distinct forebrain areas: the subfornical organ, median preoptic area,
      paraventricular nucleus, and supraoptic nucleus. In SHR, the angiotensin II
      induced c-Fos and c-Jun expressions were significantly enhanced compared with
      those in normotensive control strains as well as in secondary hypertensive Wistar
      rats. Krox-24 expression in the subfornical organ, median preoptic area, and
      paraventricular nucleus of SHR was also significantly increased compared with
      that in all control strains. In the supraoptic nucleus, significant differences
      could be discriminated between SHR and secondary hypertensive Wistar rats.
      Injection of isotonic saline or arginine vasopressin (100 ng) as controls did not
      induce any expression of c-Fos, c-Jun, or Krox-24. Our findings demonstrate an
      enhanced sensitivity of SHR to angiotensin II-induced transcription factor
      expression in distinct brain areas involved in central blood pressure and osmotic
      control that is independent of blood pressure.

PMID- 9040445
TI  - Brain 'ouabain' in the median preoptic nucleus mediates sodium-sensitive
      hypertension in spontaneously hypertensive rats.
AB  - Pressor responses to an acute increase in cerebrospinal fluid sodium and
      exaggeration of the hypertension and sympathetic hyperreactivity in spontaneously
      hypertensive rats (SHR) by high sodium diet involve release of brain "ouabain"
      and subsequent activation of the brain renin-angiotensin system. In the present
      study, we determined whether release of "ouabain" in the median preoptic nucleus
      participates in these responses. In conscious Wistar rats, the pressor and heart
      rate responses to central hypertonic saline (0.3 mol/L NaCl, 3.8 microL/min over
      10 minutes) and ouabain (0.6 microgram) were compared after median preoptic
      nucleus injection of either gamma-globulins or Fab fragments binding ouabain and
      brain "ouabain" with high affinity. Microinjection of Fab fragments into the
      median preoptic nucleus abolished the pressor and tachycardic responses to
      central hypertonic saline and significantly reduced the pressor response to
      central ouabain. In SHR on high sodium, microinjection of Fab fragments into the
      median preoptic nucleus significantly decreased baseline blood pressure to a
      level not different from that in SHR on regular sodium (149 +/- 7 versus 145 +/-
      5 mm Hg), whereas the enhanced responses to air stress were not affected. Our
      results support the concept that blood pressure responses to central hypertonic
      saline and exaggeration of the hypertension in SHR by high sodium diet depend on
      release of brain "ouabain" in the median preoptic nucleus.

PMID- 9040446
TI  - Pressure-overload deinduction of human alpha 2 Na,K-ATPase gene expression in
      transgenic rats.
AB  - The early and sustained deinduction of alpha 2 Na,K-ATPase gene expression in
      both cardiac left ventricle and aorta in various pressure-overload rat models and
      in hypertrophied human heart suggests a common transcriptional pressure response
      mechanism to pressure overload in both rats and humans. To test this hypothesis,
      we developed transgenic rat lines expressing the chloramphenicol
      acetyltransferase reporter gene regulated by the human alpha 2 Na,K-ATPase (-798
      to +67) regulatory region, H alpha 2-CAT. Analysis of two homozygous transgenic
      rat lines revealed (1) parallel tissue-specific regulation of the H alpha 2-CAT
      transgene and rat alpha 2 Na,K-ATPase gene and (2) parallel load-induced
      deinduction of both cardiac and vascular (aortic) H alpha 2-CAT transgene and rat
      alpha 2 Na,K-ATPase gene expression in a 3-day model of induced pressure
      overload. Cardiac H alpha 2-CAT deinduction was detected at a systolic pressure
      greater than or equal to 150 mm Hg and correlated with the degree of systolic
      pressure elevation (r = .82, P < .0001). The data suggest a systolic pressure
      gradient-dependent coordinate pressure-overload transcriptional response
      mechanism in the heart and aorta, with one of its target genes being the alpha 2
      Na,K-ATPase gene in both humans and rats.

PMID- 9040447
TI  - Spontaneously hypertensive rat Y chromosome increases indexes of sympathetic
      nervous system activity.
AB  - Previous studies from our laboratory have demonstrated that the Y chromosome from
      the spontaneously hypertensive rat (SHR) is responsible for a significant portion
      of the elevated blood pressure and also produces an earlier pubertal rise in
      plasma testosterone. We performed the following studies to determine whether the
      SHR Y chromosome raises blood pressure by sympathetic nervous system responses as
      measured by adrenal chromogranin A and plasma and tissue catecholamines. Male SHR
      from the University of Akron colony were studied from 5 to 20 weeks of age. Blood
      pressure was measured by tail-cuff, tail artery cannulation, and aortic telemetry
      (Data Sciences); acute (air stress) and chronic (territorial colony) social
      stressors were compared; blood was collected for determination of plasma
      catecholamines; and adrenal glands were analyzed at 15 weeks for catecholamines.
      Rats with the SHR Y chromosome had higher blood pressure and plasma
      norepinephrine than those with the normotensive Wistar-Kyoto (WKY) Y chromosome.
      However, the SHR Y chromosome did not significantly change responsiveness to
      acute or chronic stressors. Phentolamine and clonidine prevented the stress
      responses. Adrenal chromogranin A levels were elevated 37% and 40% and adrenal
      norepinephrine content 29% and 100% at 4 and 10 weeks of age, respectively, in
      rats with an SHR Y chromosome compared with WKY. Chemical sympathectomy
      normalized blood pressure in all strains and significantly reduced norepinephrine
      (36% to 41%) in all strains except in WKY, which already had a normal blood
      pressure. In conclusion, the SHR Y chromosome appears to increase the chronic
      sympathetic nervous system. A potential mechanism could be a Y locus that
      influences chronic sympathetic nervous system activity, which may reinforce
      neurohumoral factors and structural components of the vessel wall, accelerating
      the development of hypertension.

PMID- 9040448
TI  - Transfer of a salt-resistant renin allele raises blood pressure in Dahl salt
      sensitive rats.
AB  - To evaluate the role of the renin gene in the development of hypertension in Dahl
      salt-sensitive rats (SS/Jr/Hsd), we derived a congenic strain of rats homozygous
      for the salt-resistant renin allele (S/renrr) and compared them with a control
      strain homozygous for the salt-sensitive renin allele (S/ren(ss). Mean arterial
      pressure was significantly higher in 12-week-old S/renrr rats fed a high salt
      (8.0%) diet for 3 weeks than in S/ren(ss) rats or in SS/Jr/Hsd rats rederived
      from the foundation colony we used to generate the cogenic strain (195 +/- 3 [n =
      49] versus 168 +/- 3 [n = 17] or 161 +/- 3 [n = 16] mm Hg). Mean arterial
      pressure was also higher in S/renrr rats than in S/ren(ss) rats raised from birth
      on either a very low salt (0.1%) diet (119 +/- 9 [n = 6] versus 100 +/- 7 [n = 7]
      mm Hg) or a low salt (0.4%) diet (143 +/- 1 [n = 22] versus 117 +/- 3 [n = 10] mm
      Hg). Plasma renin activity of S/renrr rats was significantly higher than that of
      S/ren(ss) rats fed a very low salt diet (5.7 +/- 2.0 versus 1.8 +/- 0.3) ng
      angiotensin l/mL per hour), a low salt diet (4.4 +/- 1.0 versus 1.1 +/- 0.3), or
      a high salt diet (1.5 +/- 0.2 versus 0.9 +/- 0.1). Urinary protein excretion was
      greater in S/renrr rats than in S/ren(ss) rats fed a high salt diet (244.2 +/-
      48.5 versus 43.6 +/- 19.5 mg/24 h), and this was associated with significant
      reductions in renal blood flow (3.3 +/- 0.6 versus 4.6 +/- 0.5 mL/min per gram
      kidney weight) and glomerular filtration rate (0.49 +/- 0.11 versus 0.82 +/- 0.08
      mL/min per gram kidney weight). Captopril (20 mg/kg i.v.) had no effect on blood
      pressure in S/ren(ss) rats fed a low salt diet, but it lowered blood pressure by
      20 mm Hg in S/ren(rr) rats to the same level seen in untreated S/ren(ss) rats.
      Chronic administration of captopril (5 mg/100 mL drinking water) reduced blood
      pressure in S/renrr rats fed a high salt diet (170 +/- 5 mm Hg) to the same level
      seen in untreated S/ren(ss) rats, whereas it had no significant effect on blood
      pressure in S/ren(ss) rats. These results indicate that transfer of a salt
      resistant renin allele to SS/Jr/Hsd rats raises plasma renin activity and
      augments the severity of hypertension and renal disease.

PMID- 9040449
TI  - The angiotensinogen T235 variant and the use of antihypertensive drugs in a
      population-based cohort.
AB  - Variants of the angiotensinogen gene may increase the risk of developing arterial
      hypertension, but their effect on the use of antihypertensive medication in the
      general population remains unclear. Thus, we determined T174M and M235T allele
      status and angiotensinogen plasma levels in a cross-sectional sample of 634
      middle-aged subjects (48.4% men) from the Monitoring Trends and Determinants in
      Cardiovascular Disease (MONICA) Augsburg cohort study. We found no association
      between T174M allele status and angiotensinogen levels, blood pressure, or use of
      antihypertensive drugs. In contrast, multivariate analysis revealed that
      individuals who carried at least one copy of the T235 allele (n = 418) had higher
      systolic and diastolic pressures (P = .007) and .008, respectively) and were more
      likely to use an antihypertensive drug (1.6-fold risk, P = .04) than homozygotes
      for the M235 allele (n = 216). The likelihood of taking two or more
      antihypertensive medications was 2.1-fold higher in carriers of the T235 allele
      (P = .02). Overall, 22.5% of all antihypertensive drugs taken appeared to be
      attributable to the excess risk associated with this allele. These associations
      were replicated in two previous surveys carried out on the same individuals over
      10 years. Furthermore, the T235 allele was related to higher angiotensinogen
      plasma levels [15.5 +/- 0.31 versus 16.5 +/- 0.15 (nmol/L)/L in homozygotes for
      the M235 and T235 alleles, respectively; P < .01], which were also related to
      systolic pressure (P = .03) and more intensive antihypertensive medication (P =
      .03). We conclude that the angiotensinogen T235 allele accounts for a substantial
      proportion of antihypertensive drug use in this middle-aged, population-based
      group of white subjects.

PMID- 9040450
TI  - Additive effects of losartan and enalapril on blood pressure and plasma active
      renin.
AB  - The combination of single oral doses of an angiotensin I-converting enzyme
      inhibitor (captopril) and a type 1 angiotensin II receptor antagonist (losartan)
      has additive effects on blood pressure fall and renin release in sodium-depleted
      normotensive subjects. We planned the present study to determine whether the
      magnitude of the hemodynamic and hormonal consequences of renin-angiotensin
      system blockade by such a combination is larger than that obtained by doubling
      the dose of the angiotensin-converting enzyme inhibitor given alone. In a single
      dose, double-blind, randomized, three-way crossover study, 10 mg enalapril, 20 mg
      enalapril, and the combination of 50 mg losartan and 10 mg enalapril were
      administered orally to 12 sodium-depleted normotensive subjects. The area under
      the time curve from 0 to 24 hours (AUC0-24) of the mean blood pressure fall after
      losartan-enalapril combination intake (-220 +/- 91 mm Hg.h) was significantly
      greater than that of either 10 or 20 mg enalapril (-124 +/- 91 and -149 +/- 85 mm
      Hg.h, respectively, P < .05 vs both doses). The combination significantly
      increased by 2.3 +/- 1.2-fold the AUC0-24 of plasma active renin compared with
      either 10 or 20 mg enalapril given alone (P < .05) but had no additive effect on
      plasma aldosterone fall. The losartan-enalapril combination is more effective in
      decreasing blood pressure and increasing plasma active renin than doubling of the
      enalapril dose.

PMID- 9040451
TI  - Achievement and safety of a low blood pressure goal in chronic renal disease. The
      Modification of Diet in Renal Disease Study Group.
AB  - The Modification of Diet in Renal Disease Study showed a beneficial effect of a
      lower-than-usual blood pressure (BP) goal on the progression of renal disease in
      patients with proteinuria. The purpose of the present analyses was to examine the
      achieved BP, baseline characteristics that helped or hindered achievement of the
      BP goals, and safety of the BP interventions. Five hundred eighty-five patients
      with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2
      (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low
      BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few
      patients had a history of cardiovascular disease. All antihypertensive agents
      were permitted, but angiotensin-converting enzyme inhibitors (with or without
      diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD)
      of the mean arterial pressures during follow-up in the low and usual BP groups
      was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was
      significantly higher in subgroups of patients with preexisting hypertension,
      baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney
      disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age >
      or = 61 years, and black race. The frequency of medication changes and incidence
      of symptoms of low BP were greater in the low BP group, but there were no
      significant differences between BP groups in stop points, hospitalizations, or
      death. When data from both groups were combined, each 1-mm Hg increase in follow
      up systolic BP was associated with a 1.35-times greater risk of hospitalization
      for cardiovascular or cerebrovascular disease. Lower BP than usually recommended
      for the prevention of cardiovascular disease is achievable by several medication
      regimens without serious adverse effects in patients with chronic renal disease
      without cardiovascular disease. For patients with urinary protein excretion > 1
      g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent
      to 125/75 mm Hg.

PMID- 9040452
TI  - Different concepts in first-line treatment of essential hypertension. Comparison
      of a low-dose reserpine-thiazide combination with nitrendipine monotherapy.
      German Reserpine in Hypertension Study Group.
AB  - Low-dose combination therapy has been proposed as a rational first-line approach
      to hypertension treatment. We compared the efficacy and tolerability of the fixed
      combination of reserpine (0.1 mg) plus the thiazide clopamid (5 mg) with its
      single components and the calcium-antagonist nitrendipine (20 mg) in a
      randomized, double-blind, parallel study of 273 hypertensive patients with
      diastolic blood pressure (BP) between 100 and 114 mm Hg. The four groups did not
      differ regarding baseline characteristics (mean age, 58 years; 51% men; mean BP
      after a 2-week placebo period, 158 to 160/103 to 104 mm Hg). After 6 weeks of
      treatment with one capsule daily, mean reductions in sitting BP from baseline at
      24 hours after dosing in the reserpine-clopamid combination, reserpine, clopamid,
      and nitrendipine groups were -23.0/-17.1, -14.0/-11.7, -13.6/-11.9, and -11.6/
      12.3 mm Hg, respectively (2P < .01). The corresponding normalization rates
      (diastolic BP < 90 mm Hg) were 55%, 40%, 36%, and 33% (2P = .11). All patients
      whose BP had not been normalized at this point received two capsules of the
      respective medication once daily from weeks 7 to 12. At week 12, mean BP
      reductions were -25.7/-18.1, -14.6/-12.2, -17.7/-13.4, and -14.9/-15.3 mm Hg in
      the four groups, respectively (2P < .01). The respective normalization rates were
      69%, 35%, 39%, and 45% (2P < .0001). Linear regression modeling indicated that
      reserpine and clopamid combined acted more than additively. As regards
      tolerability, adverse experiences were observed in 27%, 28%, 29%, and 48% of
      patients, respectively (2P < .05). The respective rates of premature
      discontinuation because of adverse effects were 3%, 3%, 7%, and 13% (2P = .06).
      In conclusion, a low-dose combination of reserpine and clopamid lowered BP
      significantly more than both the components alone and nitrendipine. Moreover, the
      combination was tolerated as well as its components and significantly better than
      nitrendipine. Thus, the use of this low-dose reserpine-thiazide combination
      appears to be a rational alternative to conventional monotherapy in the first
      line treatment of hypertension.

PMID- 9040453
TI  - Determining the trough-to-peak ratio in parallel-group trials. Systolic
      Hypertension in Europe (SYST-EUR) Trial Investigators.
AB  - We explored how in parallel-group trials interindividual variability, correction
      for placebo effects, and smoothing of blood pressure profiles can be handled in
      measuring the trough-to-peak ratio in 244 individuals with isolated systolic
      hypertension (> or = 60 years) enrolled in the placebo-controlled Systolic
      Hypertension in europe Trial. Net treatment effects were computed by subtracting
      the mean changes from baseline during placebo (n = 133) from those during active
      treatment (n = 111). At entry, systolic/diastolic pressures averaged 176/86 mm Hg
      in the clinic and 149/80 mm Hg on 24-hour ambulatory monitoring. With corrections
      applied for baseline and placebo, nitrendipine (10 to 40 mg/d), with the possible
      addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25
      mg/d), reduced (P < .001) these blood pressure values by 16.6/7.3 and 9.8/4.7 mm
      Hg, respectively. The net trough-to-peak ratios were first determined from blood
      pressure profiles (12 hours) with 1-hour precision, synchronized by the morning
      and evening doses of the double-blind medication. According to the usual
      approach, disregarding interindividual variability, the systolic/diastolic net
      trough-to-peak ratios were 0.46/0.40 in the morning and 0.77/0.99 in the evening.
      In individual subjects, the baseline-adjusted trough-to-peak ratios were
      nonnormally distributed. We therefore used a nonparametric technique to calculate
      the net trough-to-peak ratios from the results in individual subjects. In the
      morning, these ratios averaged 0.25 systolic (95% confidence interval, 0.09 to
      0.41) and 0.15 diastolic (95% confidence interval, 0.00 to 0.31) and in the
      evening, 0.19 and 0.36 (95% confidence intervals, 0.00 to 0.38 and 0.14 to 0.56),
      respectively. When the blood pressure profiles were smoothed by substituting the
      1-hour averages by moving or fixed 2-hour averages or by Fourier modeling, the
      trough-to-peak ratios remained unchanged after the morning dose (0.20/0.13,
      0.20/0.14, and 0.16/0.21, respectively) but tended to increase in the evening
      (0.32/0.38, 0.28/0.40, and 0.48/0.49). In conclusion, the parallel-group analysis
      proposed makes it possible for one to correct the trough-to-peak ratio for
      baseline as well as placebo, to account for interindividual variability, and to
      calculate a confidence interval for the net trough-to-peak ratio. Accounting for
      interindividual variability reduces the trough-to-peak ratio. Smoothing affects
      the individualized net trough-to-peak ratios in an unpredictable way and should
      therefore be avoided.

PMID- 9040454
TI  - N-acetylcysteine does not influence the activity of endothelium-derived relaxing
      factor in vivo.
AB  - Nitric oxide forms complexes with an array of biomolecular carriers that retain
      biological activity. This reactivity of nitric oxide in physiological systems has
      led to some dispute as to whether endothelium-derived relaxing factors nitric
      oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro
      bioassays used to address this question are limited by the exclusion of
      biological thiols that are requisite for nitrosothiol formation. Thus, the
      purpose of this study was to obtain insight into the identity of endothelium
      derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing
      factor in nitric oxide, infusion of physiological concentrations of thiol would
      potentiate its bioactivity by analogy with effects seen in vitro, whereas
      nitrosothiol would be resistant to such modulation. We used venous-occlusion
      plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3
      to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via
      the brachial artery to elicit endothelium-dependent and endothelium-independent
      vasodilation, respectively. Dose-response determinations were made for each drug
      before and after an intra-arterial infusion of the reduced thiol, N
      acetylcysteine, at rates estimated to achieve a physiological concentration of 1
      mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner.
      Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7
      micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol
      increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min,
      P < .01). Thus, conflicting with reports in vitro, thiol does not modulate
      endothelium-derived relaxing factor responses in vivo. These data indicate that
      sulfhydryl groups are not a limiting factor for endothelium-derived relaxing
      factor responses in forearm resistance vessels in normal humans and are in
      keeping with reports that nitrosothiol contributes to endothelium-derived
      relaxing factor bioactivity in plasma and vascular smooth muscle. Potentiation of
      the effects of nitroglycerin by N-acetylcysteine can be attributed to its
      enhanced biotransformation to an endothelium-derived relaxing factor equivalent,
      such as nitrosothiol. These observations support the notion of an equilibrium
      between nitric oxide and nitrosothiol in biological systems that may be
      influenced by redox state.

PMID- 9040455
TI  - Association of body mass index with blood pressure in elderly Japanese American
      men. The Honolulu Heart Program.
AB  - Few data are available on the association between body mass index (BMI) and blood
      pressure in elderly individuals, particularly among minority groups. We studied
      the cross-sectional association of BMI with systolic and diastolic pressures in
      1378 Japanese American men 60 to 82 years of age who were participants in the
      population-based Third Lipoprotein Examination of the Honolulu Heart Program
      conducted between 1980 and 1982. When the subjects were divided into 5-year age
      groups, mean BMI decreased linearly with increasing age. Mean systolic pressure
      rose from 134.8 mm Hg in the first quintile of BMI to 138 in the second and 141.8
      in the third quintiles, with levels of 139.2 and 142 in the fourth and fifth
      quintiles, respectively (test for trend, P = .083). Mean diastolic pressure rose
      from 78.1 mm Hg in the lowest quintile of BMI to 83.9 in the highest (test for
      trend, P = .008). We performed multiple regression analysis, controlling for
      factors known to influence blood pressure values, including age, physical
      activity index, alcohol intake, current smoking status, and diabetes mellitus.
      The association between BMI and both systolic and diastolic pressures remained
      highly statistically significant in these analyses. These results show that
      obesity and high blood pressure continue to be highly correlated even in old age
      and suggest that it may be possible to modify rates of hypertension by changes in
      body weight.

PMID- 9040456
TI  - Alpha 1-adrenergic receptor antibodies in patients with primary hypertension.
AB  - Autoimmune mechanisms have been proposed to play a role in the pathogenesis of
      primary (essential) hypertension. Autoantibodies against the alpha 1-adrenergic
      receptor have been described in patients with malignant and secondary
      hypertension. To investigate the incidence of autoantibodies against the alpha 1
      adrenoceptor in patients with primary hypertension, we examined the
      immunoglobulin fractions of sera from 54 patients with primary hypertension and
      26 normotensive control subjects for the presence of autoantibodies against the
      alpha 1-adrenoceptor. Sera from 24 patients (44%) and 3 subjects (12%) were
      positive. An epitope analysis of 16 autoantibody-positive immunoglobulin
      fractions revealed that in two thirds of the cases, the antibodies were directed
      against the first extracellular loop of the alpha 1-adrenoceptor and in one
      third, against the second. The autoantibodies had a positive chronotropic effect
      on isolated neonatal rat cardiomyocytes, an effect that was blocked by alpha 1
      adrenergic antagonists. Since the functional characteristics of the
      autoantibodies showed no desensitization phenomena, they may play a role in
      elevating peripheral vascular resistance and promoting cardiac hypertrophy in
      patients with primary hypertension.

PMID- 9040458
TI  - Neuronal coupling in rod-signal pathways of the retina.

PMID- 9040457
TI  - Effects of chronic arterial hypertension on constitutive and induced
      intercellular adhesion molecule-1 expression in vivo.
AB  - Recent reports indicate that bacterial endotoxin (lipopolysaccharide) and
      cytokines elicit a more profound increase in the surface expression of
      intercellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells derived
      from spontaneously hypertensive (SHR) versus normotensive Wistar-Kyoto rats
      (WKY). Our objective in this study was to characterize and compare in vivo ICAM-1
      expression in SHR and WKY under basal conditions and after 5 hours of endothelial
      cell activation with either lipopolysaccharide (5 mg/kg i.p.) or tumor necrosis
      factor-alpha (TNF-alpha; 1, 5, and 10 micrograms/kg i.p.). ICAM-1 expression was
      quantified in different tissues by the double-radiolabeled monoclonal antibody
      technique. When constitutive (baseline) ICAM-1 expression was corrected for
      endothelial cell surface area, significantly higher values were noted in SHR than
      WKY but only in splanchnic organs. Lipopolysaccharide and TNF-alpha elicited
      significant increases in ICAM-1 expression in all tissues of both WKY and SHR.
      However, the magnitude of the lipopolysaccharide-induced ICAM-1 upregulation in
      heart, stomach, skeletal muscle, and brain was significantly lower in SHR than
      WKY. A similar blunted ICAM-1 upregulation was noted in the stomach of SHR after
      administration of 5 micrograms/kg TNF-alpha. The differences in induced ICAM-1
      expression between SHR and WKY do not appear to be due to differences in
      endothelial cell surface area or plasma glucocorticoid levels. These results
      suggest that chronic arterial hypertension results in altered ICAM-1 expression
      on the endothelium, which may contribute to the abnormal inflammatory responses
      associated with this disease.

PMID- 9040459
TI  - Corneal neovascularization induced by xenografts or chemical cautery. Inhibition
      by cyclosporin A.
AB  - PURPOSE: Neovascularization of the cornea occurs in numerous pathologic states
      causing decreased visual acuity and blindness and is a major complication of
      corneal allotransplantation. The purpose of this study was to investigate the
      effect of topical and systemic cyclosporin A (CsA) on corneal angiogenesis
      induced by xenotransplantation or by chemical cauterization. The subcutaneous
      disc angiogenesis system (DAS) also was used to study the effects of CsA on
      angiogenesis in a nonocular site. METHODS: Corneal angiogenesis was provoked by
      either xenotransplantation or chemical cautery. Rats from experiments using both
      of these models were subdivided into four treatment groups. Topical treatment was
      administered by using 4% CsA eye drops or vehicle (castor oil) four times daily
      for 10 days. Systemic therapy consisted of daily (5 mg/kg per day) subcutaneous
      injections of CsA or vehicle. In the DAS experiments, rats received CsA or
      vehicle systemically or intradisc. The amount of neovascularization was
      quantitated by digital image analysis in corneal flat preparations and sections
      of discs. RESULTS: Rats that received xenografts or cautery manifested less
      corneal neovascularization than did control animals after topical of subcutaneous
      CsA treatment. CsA also enhanced the survival of corneal xenografts. A difference
      between CsA and vehicle-treated animals in the DAS experiments was not detected.
      CONCLUSIONS: CsA effectively retards the growth of new vessels in the cornea
      after xenotransplantation or chemical cauterization and prolongs xenograft
      survival. However, CsA does not suppress angiogenesis in all systems, because it
      was ineffective in blocking vessel growth in the subcutaneous DAS.

PMID- 9040460
TI  - Apoptotic retinal cell death induced by antirecoverin autoantibodies of cancer
      associated retinopathy.
AB  - PURPOSE: Recoverin has been identified as a target autoantigen for antirecoverin
      antibodies found in the sera of some patients with cancer-associated retinopathy.
      The aim of this study was to investigate the role of antirecoverin antibodies in
      cancer-associated retinopathy. METHODS: Human, rat, and rabbit antirecoverin
      antibodies were purified using a recoverin-affinity column. Purified biotinylated
      antibodies were cultured with recoverin-positive rat retinal cells E1A.NR3.
      Antibody uptake by retinal cells in vitro was analyzed by immunocytochemistry.
      Cytotoxic effect of antibodies on retinal cells was measured by the MTT
      colorimetric method. Apoptosis was shown by the ladder DNA fragmentation method
      and by fluorescent dye chromatin fragmentation analysis. RESULTS: Antirecoverin
      antibodies obtained either from sera from five cancer-associated retinopathy
      patients or from sera of immunized animals were internalized by E1A.NR3 cells.
      Only specific, antirecoverin antibodies produced destruction of the cells in a
      dose- and time-dependent manner. Normal immunoglobulin G did not have such
      effects on retinal cells. No additional cell destruction was observed in the
      presence of complement as compared with cultures incubated with antirecoverin
      antibodies alone. Internucleosomal DNA fragmentation and presence of apoptotic
      cells was observed throughout the culture treated with recoverin specific
      antibodies but not with normal antibodies. Cells not expressing recoverin (Y79,
      PC12, and GH3) were not susceptible to cell destruction because of antirecoverin
      antibody action. CONCLUSIONS: These studies showed that antibodies specific to
      recoverin are able to enter and cause death of cells expressing recoverin. In
      humans, autoantibodies originally elicited against recoverin expressed in tumor
      cells may damage retinal photoreceptors and play a role in the pathogenesis of
      cancer-associated retinopathy. Results suggest that autoantibody to recoverin,
      when given access to recoverin in the retina through the blood-retina barrier,
      could initiate photoreceptor degeneration leading to blindness. Such mechanism
      may be common for other paraneoplastic disorders or autoimmune diseases where
      antibodies interfere with the normal cell physiology.

PMID- 9040461
TI  - Correlation of anterior chamber-associated immune deviation with suppression of
      corneal epithelial rejection in mice.
AB  - PURPOSE: The authors investigated the effect of anterior chamber corneal (AC)
      inoculation of genetically graft-identical antigen on T-cell immunity and the
      suppression of alloepithelial rejection in mice. METHODS: Antigen-specific
      suppression of delayed-type hypersensitivity (DTH) and suppression
      transferability were tested in BALB/c mice injected with irradiated allogeneic
      B10.D2 splenocytes into AC. Other groups of BALB/c mice received irradiated
      B10.D2, BALB/c, or C3H/He splenocytes in the AC of the right eye. Seven days
      later, B10.D2 or C3H/He corneal lenticules were grafted at the limbus of the left
      eye (keratoepithelioplasty). Alloepithelial rejection of each grafted eye was
      evaluated according to clinical findings. The DTH response of the
      keratoepithelioplasty recipients against B10.D2 minor antigen was tested at the
      end of clinical observation (4 months after grafting). Also examined was spleen
      component transfer from BALB/c mice with AC inoculation of B10.D2 splenocytes to
      syngeneic acceptors and its effect on suppression of epithelial rejection against
      B10.D2 antigen. RESULTS: Inoculation of B10.D2 splenocytes into BALB/c AC induced
      antigen-specific DTH suppression, which suppression was transferable. During the
      4-month observation period, AC inoculation of B10.D2 minor antigen significantly
      enhanced the survival of B10.D2-derived epithelium, but not of C3H/He-derived
      epithelium, in BALB/c mice. However, AC inoculation of BALB/c or C3H/ He
      splenocytes did not enhance B10.D2 epithelial survival in BALB/c mice.
      Incapability of antigen-specific DTH response generation was observed in the
      BALB/c mice with B10.D2 splenocytes in the right AC and B10.D2-derived epithelium
      in the left eye. Single transfer of spleen components from BALB/c mice with AC
      inoculation of B10.D2 splenocytes to syngeneic acceptors only delayed B10.D2
      minor antigen-stimulated epithelial rejection, whereas supplementary transfers of
      the identical spleen components at different time intervals showed more
      significant effect in rejection delay. CONCLUSIONS: The results showed that AC
      inoculation of B10.D2 splenocytes in BALB/c mice induced antigen-specific
      suppression of DTH response, in a phenomenon termed anterior chamber-associated
      immune deviation (ACAID). It also was shown definitely that ACAID can suppress
      alloepithelial rejection in a murine keratoepithelioplasty model. Adoptive
      transfer of splenocytes from ACAID-induced mice merely affords short-term
      suppression of epithelial rejection, suggesting that an additional mechanism may
      be involved in ACAID maintenance.

PMID- 9040462
TI  - Adoptive transfer of murine cytomegalovirus-immune lymph node cells prevents
      retinitis in T-cell-depleted mice.
AB  - PURPOSE: The purpose of this study was to determine whether adoptive transfer of
      murine cytomegalovirus (MCMV)-immune lymph node cells prevents retinitis in
      immunosuppressed mice. METHODS: Adult BALB/c mice were thymectomized and T-cell
      depleted using rat monoclonal antibodies specific for mouse CD4+ and CD8+ T
      cells. The level of rat immunoglobulin G in the treated mice was monitored by
      enzyme-linked immunosorbent assay. Immune cells were labeled with PKH26-GH
      immediately before adoptive transfer, and flow cytometry was used to determine
      the percentage of adoptively transferred T-cells (PKH+, fluorescein
      isothiocyanate [FITC+]) in the spleens of the recipient mice 3 days after
      transfer. The ability of adoptively transferred cells to protect from retinitis
      was studied in T-cell-depleted mice injected with MCMV through the supraciliary
      route. Mice received 4 x 10(7) in vitro-restimulated MCMV-immune cells, 4 x 10(7)
      freshly isolated MCMV-immune cells, 4 x 10(7) freshly isolated ovalbumin-immune
      cells, or no cells (control group). RESULTS: The best time to balance depletion
      of endogenous T-cells with persistence of transferred cells was 3 weeks after T
      cell depletion. Both restimulated and freshly isolated MCMV-immune cells
      conferred protection from retinitis. Freshly isolated ovalbumin-immune lymph node
      cells did not prevent retinitis, indicating that protection was virus-specific
      and merely was not because of transfer of antigen-activated lymph node cells.
      CONCLUSIONS: Adoptive immunotherapy has been used to prevent cytomegalovirus
      (CMV) infection in patients who have undergone transplantation, and, by
      extrapolation, the results of these studies suggest that adoptive immunotherapy
      with human CMV-specific immune cells might be used to prevent or ameliorate CMV
      retinitis in immunocompromised patients.

PMID- 9040463
TI  - Corneal topography and myopia. A cross-sectional study.
AB  - PURPOSE: Central corneal curvature is known to vary with refractive error, but
      the relation between corneal topography and ametropia is less clear. The current
      study was conducted to determine whether a relation exists between corneal
      asphericity and myopia. Associations between corneal asphericity and each of the
      components of refraction also were examined. METHODS: Corneal asphericity and
      apical radius of curvature were determined for 113 eyes (spherical equivalent
      refractive error +0.25 diopter [D] to -9.88 D) by fitting a conicoid equation to
      videokeratoscopic data. Computerized videokeratoscopic images were recorded using
      a Topographic Modeling System. Keratometry also was performed on each eye.
      Anterior chamber depth, lens thickness, vitreous chamber depth, and axial length
      were measured with a hand-held biometric ruler. RESULTS: A low but statistically
      significant positive correlation was found between corneal asphericity (Q) and
      spherical equivalent refractive error (r = 0.275, P < 0.01). Significant
      relations also were observed between Q and vitreous chamber depth (r = 0.17, P <
      0.1) and between Q and axial length (r = 0.24, P < 0.05). The association between
      Q and corneal radius of curvature was found not to be significant. Eyes with
      higher levels of myopia had steeper central corneal curvatures, deeper anterior
      and vitreous chambers, and greater axial lengths. CONCLUSIONS: A tendency for the
      cornea to flatten less rapidly in the periphery with increasing myopia was shown.
      Decreased peripheral corneal flattening also was observed in association with
      increasing vitreous chamber depth and increasing axial length. These findings
      have implications for refractive surgery outcomes, schematic eye modeling,
      contact lens design, and ocular aberration analysis.

PMID- 9040464
TI  - A longitudinal investigation of adult-onset and adult-progression of myopia in an
      occupational group. Refractive and biometric findings.
AB  - PURPOSE: To investigate the refractive and biometric changes associated with
      adult-onset and adult-progression of myopia in an occupational group. METHODS:
      The sample population consisted of 251 clinical microscopists aged 21 to 63
      years. Subjects had their refraction and ocular dimensions measured on four
      occasions during a 2-year period, and a total of 166 subjects (332 eyes)
      completed the longitudinal aspect of the study. Refraction was measured
      objectively with a Canon R-1 autorefractor and subjectively by an optometrist
      using standard procedures. Corneal curvature and axial ocular dimensions were
      measured with a keratometer and A-scan ultrasonography, respectively. RESULTS: Of
      eyes emmetropic at the start of the study, a total of 39% underwent a myopic
      change in refraction greater than 0.37 diopter (D), with a mean change of -0.58
      +/- 0.04 D (mean +/- standard error of the mean; n = 37). This was associated
      with an elongation of the vitreous chamber of 0.26 +/- 0.05 mm (P < 0.01). Eyes
      emmetropic at the start of the study that did not undergo a refractive change >
      0.37 D (n = 58) during the 2-year study period had a mean change in refraction of
      0.02 +/- 0.03 D (P = 0.69) associated with a change in vitreous chamber depth of
      0.05 +/- 0.02 mm. Changes in corneal curvature, anterior chamber depth, or lens
      thickness between the initially emmetropic groups were not significant. The
      median age of onset of myopia in initially emmetropic eyes was 26.3 years. Of
      eyes that were myopic at the start of the study, 48% progressed further into
      myopia by 0.37 D or more during the 2-year period. The mean increase in myopia
      for the "myopia progressor" group was 0.77 +/- 0.03 D (n = 108 eyes) compared to 
      0.01 +/- 0.02 D (n = 115 eyes; P = 0.49) for myopes who did not undergo a
      refractive change > 0.37 D during the study period. The only significant
      difference in ocular component dimension changes during the study period for
      these two initially myopic groups was elongation of the vitreous chamber depth
      (0.24 +/- 0.04 mm versus 0.03 +/- 0.03 mm, P < 0.01). The average age of the
      myopes who progressed further into myopia during the study was 29.3 years. Axial
      length-corneal radius ratio at the start of the study was not significantly
      different between initially emmetropic eyes in which adult onset myopia developed
      or emmetropic eyes that remained refractively stable. The incidence of adult
      myopia development during a 2-year period in this occupational group was 45%.
      CONCLUSIONS: The structural cause of adult-onset and adult-progression of myopia
      is vitreous chamber elongation.

PMID- 9040465
TI  - Prevalence and risk factors for refractive errors in an adult inner city
      population.
AB  - PURPOSE: To estimate the prevalence of refractive errors among adult black and
      white Americans and to identify risk factors associated with these refractive
      errors. METHODS: Refractive error was measured in a population-based sample of
      black and white adults age 40 or older residing in east Baltimore from 1985
      through 1988. Aphakic eyes were excluded from analysis. RESULTS: The prevalence
      of myopia varied from 10.5% among black men 80 years and older to 42.1% among
      white women 40 to 49 years of age. Hyperopia ranged from 11.8% among black men 40
      to 49 years to 68.1% among white men 80 years of age and older. Astigmatism
      ranged from 15.8% to 45.2%, and anisometropia ranged from 2.8% to 8.1%, depending
      on age, race, and gender. Black persons had less myopia, hyperopia, astigmatism,
      and anisometropia than did white persons. Myopia (< -0.5 diopter [D] spherical
      equivalent) declined with age, whereas hyperopia (> +0.5 D), astigmatism (> 0.5 D
      of cylinder), and anisometropia (> 1.0 D between eyes) increased with age. Myopia
      increased with increasing years of education, although this association was
      stronger for white persons than for black persons and among younger subjects.
      Hyperopia declined with increasing years of education, and this association was
      stronger among younger than older subjects. Education was not associated with
      astigmatism or anisometropia. CONCLUSIONS: Black persons had lower rates of
      refractive error than did white persons, except for hyperopia prevalence, which
      was comparable in black and white women. Refractive errors are common among adult
      inner city Americans, but rates vary substantially by age, race, gender, and
      education levels.

PMID- 9040466
TI  - Connexin distribution in the rabbit and rat ciliary body. A case for heterotypic
      epithelial gap junctions.
AB  - PURPOSE: To evaluate the distribution of different alpha- and beta-type connexins
      (Cx) present in the dual layered ciliary body epithelia (CBE) of both rabbit and
      rat. METHODS: Immunocytochemical detection of Cx26, Cx32, Cx43, and Cx50 was
      performed on frozen sections of rabbit and rat ciliary body using indirect
      immunofluorescent methods. The identity of the antigens recognized by the
      monoclonal primary antibodies was further confirmed by Western immunoblots.
      Double labeling experiments based on either conventional or confocal microscopy
      were carried out to establish the exact spatial relationship between different
      connexins. RESULTS: Connexin 50 was found only in the nonpigmented epithelium
      (NPE) at apical and basolateral membranes, whereas Cx43 was observed exclusively
      and at a very high concentration in the pigmented epithelium (PE), primarily in
      the apical cell membrane, with minimal extension to the proximal lateral zone.
      The correct antigenicity of the antibodies was confirmed by Western blots of
      rabbit ciliary body membranes. In rabbit, the Cx26 antibody detected an antigen
      that was abundant in the NPE and was weakly expressed in the PE. In rat, however,
      the Cx26 staining was confined to capillary wall endothelia. Western blots of
      ciliary body and liver membranes and liver immunohistology indicated that the
      Cx26 antibody used does not recognize rabbit Cx26. Cx32 did not yield any
      substantial epithelial labeling in either species. CONCLUSIONS: The distribution
      of Cx50 around the entire NPE cell perimeter suggests its involvement in NPE-NPE
      cell homotypic gap junctions. The concentration of Cx43 and Cx50 at the apical
      membranes of the PE and NPE cells, respectively, and their complete absence from
      the opposite cell suggest that these connexins may participate in the formation
      of heterotypic gap junctions, either with each other or with other yet
      unidentified connexins.

PMID- 9040467
TI  - Calponin distribution in human ciliary muscle and other anterior segment tissues.
AB  - PURPOSE: Calponins are a family of actin-binding proteins known to regulate
      aortic and tracheal smooth muscle contraction. This investigation was undertaken
      to assess the presence, subtype, and distribution of calponin proteins in human
      ciliary muscle, iris, and other anterior segment tissues as well as expression in
      ciliary muscle cells in vitro. METHODS: The distribution of calponin
      immunoreactivity was assessed in paraffin sections of human anterior segment
      tissue. Human ciliary muscle proteins were analyzed by polyacrylamide gel
      electrophoresis and Western blotting. The regulation of calponin expression was
      compared with alpha-sm-actin expression in preconfluent and postconfluent ciliary
      muscle cell cultures by immunocytochemistry. To determine total cell counts, the
      cultures were counter-stained with ethidium homodimer. As control specimens,
      expression of calponin and alpha-sm-actin also was assessed in human Tenon
      fibroblast cultures. RESULTS: Strong calponin immunoreactivity was present in
      ciliary muscle, iris dilator and sphincter muscles, and blood vessel smooth
      muscle. Fine immunostained strands also were observed in the scleral spur. This
      distribution was similar to alpha-sm-actin. Western blotting showed a single band
      of calponin with a molecular weight of 32 kDa. In the cultured ciliary muscle
      cells, calponin stained straight cable-like fibers running parallel along the
      long axis of the cells. Although the proportion of calponin immunoreactive cells
      was reduced substantially in preconfluent cultures, virtually all cells were
      stained in confluent primary through fourth-passage cultures. Cultured human
      Tenon fibroblasts did not show either calponin or alpha-sm-actin
      immunoreactivity. CONCLUSIONS: Calponin is expressed in human ciliary muscle,
      iris smooth muscles, blood vessel smooth muscle, as well as within the scleral
      spur. In addition, calponin is expressed by ciliary smooth muscle cells in vitro.
      The role of calponin in contraction of these tissues should be investigated.

PMID- 9040468
TI  - Biomechanical characteristics of the human anterior lens capsule in relation to
      age.
AB  - PURPOSE: The purpose of the study was to investigate the influence of age on the
      biomechanical properties of the human anterior lens capsule. METHODS: The
      material comprised 67 lens capsules obtained from human donors ranging in age
      from 7 months to 98 years. Test specimens were prepared from the anterior lens
      capsule as tissue rings by means of excimer laser technique using a metal ring
      (mask) to shape the laser output (outer diameter = 3.2 mm, width = 100 microns).
      Capsular thickness was measured under microscope as the difference in focus
      between microspherules placed on the outer and inner surfaces of the capsule. The
      rings were slipped over two pins connected to a motorized micropositioner and a
      force transducer, respectively, and stretched at constant speed until rupture,
      with continuous recording of load and elongation. RESULTS: Capsular thickness was
      associated significantly with age of the donors and increased gradually (1.2% per
      year) until age 75, after which a slight decrease was observed. The elastic
      response curves showed a high degree of nonlinearity and were influenced markedly
      by age. Ultimate strain decreased 0.5% per year (range, 108% to 40%). Ultimate
      tensile strength decreased 1% per year (range, 17.5 N/mm2 to 1.5 N/mm2), and
      ultimate elastic stiffness (tangent modulus) decreased 0.9% per year (range, 44.8
      N/mm2 to 4.4 N/mm2), whereas elastic stiffness corresponding to a specific strain
      level (30%) increased until age 35, after which a slight decrease was observed.
      CONCLUSIONS: Aging of the human anterior lens capsule is associated with a
      progressive loss of mechanical strength. The young capsule is strong, tough, and
      highly extensible, whereas the older, thicker capsule is less extensible and much
      more brittle, and it has a markedly reduced breaking strength.

PMID- 9040469
TI  - Distinguishing subcortical and cortical influences in visual attention.
      Subcortical attentional processing.
AB  - PURPOSE: The purpose of the study was to investigate the role of subcortical
      processing in human visual attention. The midbrain contribution to visual
      attention is unclear. Although evidence exists for a subcortical attentional
      advantage in ocular motor tasks, such an advantage has not been shown in
      perceptual tasks. Because retinotectal projections arise predominantly from nasal
      retina (i.e., temporal hemifield), subcortical attention should be distributed
      asymmetrically for monocular viewing conditions with an advantage to the temporal
      hemifield. METHODS: To test for a subcortical attentional effect, the authors
      compared the results of binocular and monocular viewing conditions using the
      split priming motion induction paradigm. In this perceptual attention paradigm,
      priming cues are presented to the left and right of fixation followed by an
      instantaneously presented horizontal bar. As a result of attention to the priming
      cues, motion is perceived within the bar as it appears to draw in from the two
      lateral cues toward a central collision point. Asymmetrically distributed
      attention results in an asymmetry in the perception of motion within the bar, and
      thus the perceived collision point will be shifted away from the center. RESULTS:
      In two separate studies, one with and one without control of eye movements, the
      authors found significant differences between the results for monocular and
      binocular presentation. When the stimulus configuration is presented to the left
      eye, the perceived collision point is shifted toward the center consistent with a
      subcortical attentional effect. However, presentation of the stimulus
      configuration to the right eye yields the same results as those of binocular
      presentation. CONCLUSIONS: This pattern of results can be explained by a separate
      and additive interaction between cortical and subcortical attentional effects in
      the visual field. Dominance of the left visual field for cortical attention and
      dominance of the temporal visual field for subcortical attention act together
      when the initial priming cue occurs in the temporal (left) visual field of the
      left eye. However, these influences compete when the same stimulus configuration
      is presented to the right eye, where cortical attention predominates in the left
      visual field and subcortical attention predominates in the temporal (right)
      visual field.

PMID- 9040470
TI  - Activation of protein tyrosine phosphorylation after retinal branch vein
      occlusion in cats.
AB  - PURPOSE: The authors examine the effect of retinal branch vein occlusion (BVO), a
      common retinal vascular disorder, on protein tyrosine phosphorylation, production
      of angiogenic growth factors, and activation of signal proteins in the tyrosine
      kinase pathways in the retina. METHODS: Retinal branch vein occlusion was induced
      in cat retina by coagulation of retinal veins with diathermy. At 2 days, 1, 3,
      and 6 weeks after induction of BVO, the retina was divided into three parts: a
      part within the distribution of the occluded vein (BVO[IN]) or a part outside the
      distribution of the occluded vein (BVO[OUT]). Each part of the retina was
      prepared for Western blot analysis of tyrosine-phosphorylated proteins, vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and four
      signal proteins in the tyrosine kinase pathways, which were phospholipase C gamma
      (PLC gamma), C-Src, SH2-containing protein (SHC), and mitogen-activated protein
      kinase (MAPK). RESULTS: Overall, tyrosine-phosphorylated proteins were increased
      after BVO, especially in BVO(IN) at 2 days and 1 week. The VEGF and bFGF also
      were increased in BVO(IN) at 1 week and 2 days, respectively. The PLC gamma and
      MAPK were activated at these time points. The C-Src and SHC were not activated in
      the retina after BVO. CONCLUSIONS: The BVO increased overall protein tyrosine
      phosphorylation in the cat retina in association with increase of angiogenic
      growth factors (VEGF and bFGF) and activation of two signal proteins (PLC gamma
      and MAPK) in the tyrosine kinase pathways. These results suggest that the protein
      tyrosine phosphorylation may in part play an important role in mitogenesis of
      vascular endothelial cells and other retinal responses after BVO.

PMID- 9040471
TI  - Structure and composition of rat precorneal tear film. A study by an in vivo
      cryofixation.
AB  - PURPOSE: To visualize the in vivo structure and to investigate the composition of
      rat precorneal tear film. METHODS: An in vivo cryofixation with freeze
      substitution method of electron microscopy was used for the study. For light and
      transmission electron microscopy, a small amount of aluminum powder was used as a
      tracer spread on the corneal surface. The eyeballs were immediately and quickly
      frozen by pouring an isopentane-propane mixture cooled by liquid nitrogen
      directly over the eyes. For scanning electron microscopy, the corneal surface was
      freeze-fractured after the cryofixation. The specimens were then freeze
      substituted and prepared conventionally for microscopic observation. RESULTS: The
      tear film appeared as a layer of homogeneous and fine network-like structures
      varying from 2 to 6 microns in thickness on the corneal surface, with a membrane
      like layer covering its surface. The aluminum powder was located on the surface
      of the tear film. The tear film could be removed completely by applying 10% or
      20% acetylcysteine, but not by phosphate buffer. CONCLUSIONS: The in vivo
      structure of the rat tear film is composed primarily of mucus, with a lipid layer
      covering its surface but without a free aqueous layer. The "three layers theory"
      of tear film structure requires revisions.

PMID- 9040472
TI  - Topical substance P and corneal epithelial wound closure in the rabbit.
AB  - PURPOSE: The authors determined the effect of topically applied substance P (SP)
      on the rate of corneal epithelial wound closure in the rabbit. METHODS: Uniform
      circular lesions, 6.5 mm in diameter, were made bilaterally in the corneal
      epithelium of 24 rabbits using N-heptanol. Substance P was applied repeatedly to
      one eye, and the SP1-7 fragment was applied to the contralateral (control) eye
      until wound closure was obtained. Three concentrations of peptide solution (5 x
      10(-5) M, 5 x 10(-4) M, and 5 x 10(-3) M) were tested in separate groups of eight
      animals each. An additional eight animals received topical applications (5 x 10(
      7) M) of the neurokinin-1 (NK1)-specific SP receptor antagonist CP-99,994-01 or
      its ineffective enantiomer CP-100,263-01. The mean rates of wound healing for
      each group of experimental and control eyes were determined by linear regression
      and analyzed by analysis of variance. RESULTS: There were no statistically
      significant differences in the mean rates of wound closure (range, 0.083 to 0.106
      mm/hour) between experimental- and control-treated corneas for any of the four
      groups tested. CONCLUSIONS: The topical application of SP or its NK1 receptor
      antagonist has no significant effect on the rate of corneal epithelial wound
      closure in the rabbit.

PMID- 9040473
TI  - Human lens epithelial cell proliferation in a protein-free medium.
AB  - PURPOSE: The ocular humors are relatively low in protein, yet cell growth in the
      human capsular bag still occurs after extracapsular cataract extraction (ECCE)
      surgery. This resilient growth gives rise to posterior capsule opacification
      (PCO) in a significant proportion (30%) of patients. This study compared the
      ability of human lens cells to proliferate in serum-supplemented and protein-free
      medium. METHODS: Sham cataract operations were performed on human donor eyes. The
      capsular bag was dissected free, pinned flat on a petri dish, and incubated in
      Eagle's minimal essential medium (EMEM) alone or in EMEM supplemented with 10%
      fetal calf serum. Observations were made by phase-contrast microscopy. At the
      endpoint, capsules were studied by fluorescence or electron microscopy. Mitotic
      activity was identified using Bromo-2-deoxyuridine labeling and detection
      techniques. When required, an intraocular lens was implanted when surgery was
      performed. RESULTS: It was found that human lens cells from a wide age spectrum
      of donors proliferate and migrate on the lens capsule in the absence of added
      protein. The rate of growth was age-dependent, such that the posterior capsule
      was completely confluent after 8.0 +/- 0 days (n = 3) and 24.4 +/- 5.3 days (n =
      3) for donor lenses aged < 40 years and > 60 years, respectively. The outgrowth
      of epithelial cells gave rise to capsular contraction, wrinkling, and increased
      light scatter. Growth on the anterior surface of the intraocular lens was less
      prolific than on the posterior capsule. CONCLUSION: The protein-free model
      replicates many features of clinically-observed PCO. The resilient cell growth on
      the natural collagen capsule explains the high prevalence of PCO, especially in
      younger patients, and suggests that inflammation and external growth factors are
      not necessary for PCO. Furthermore, the protein-free capsular bag system can be
      used to explore fundamental questions concerning the autocrine control of lens
      epithelial cell survival and growth.

PMID- 9040474
TI  - Investigations on subjective and objective cyclorotatory changes after inferior
      oblique muscle recession.
AB  - PURPOSE: To determine subjective and objective cyclorotatory changes after
      surgery for oblique muscle disorders and to analyze the mechanisms of the well
      known, long-term, postoperative, subjective cyclotorsional changes. METHODS:
      Twenty-six patients underwent unilateral inferior oblique muscle recession for
      strabismus sursoadductorius (inferior oblique overfunction). Subjective and
      objective cyclodeviation were examined before surgery with and without diagnostic
      occlusion, as well as 1 day, 3 days, and 4 months after surgery. Subjective
      cyclodeviation was assessed by Harms' tangent scale. Objective cycloposition was
      measured by means of fundus cyclometry, a novel method using an infrared scanning
      laser ophthalmoscope. RESULTS: Diagnostic occlusion did not lead to significant
      changes in either objective or subjective cyclodeviation. Preoperative objective
      excycloposition was nearly equally distributed between affected eyes and fellow
      eyes. Early surgically induced incyclorotatory effects were more pronounced
      objectively than subjectively. On long-term follow-up, a reduction in the
      incyclorotatory effect was found to be smaller subjectively than objectively. A
      significant difference between subjective and objective cycloposition was seen
      early after surgery, and a significant difference between subjective and
      objective cyclorotatory change was found immediately after surgery and on long
      term follow-up. CONCLUSIONS: Long-term regression of the incyclorotatory effect
      after inferior oblique muscle recession was confirmed objectively and
      subjectively and can be explained as a cessation of preoperatively required
      binocular compensatory innervation. The authors conclude that the difference
      between objective and subjective regression is caused by sensory cyclofusion.

PMID- 9040475
TI  - Screening for glaucomatous visual field loss with frequency-doubling perimetry.
AB  - PURPOSE: To conduct a preliminary evaluation of the efficacy of the frequency
      doubling contrast test as a means of screening for glaucomatous visual field
      loss. METHODS: Contrast thresholds for frequency-doubled stimuli were obtained
      under four test conditions: superior hemifield, inferior hemifield, and central
      (5 degrees radius) targets using a method of adjustment (MOA); superior
      hemifield, inferior hemifield, and central targets using a modified binary search
      (MOBS); four quadrant stimuli and the central target using MOBS; and 16 stimuli
      (four per quadrant) and the central target using MOBS. One eye each of 36
      patients with early (12), moderate (12), and advanced (12) glaucomatous visual
      field loss was tested, as was one eye each of 36 age-matched normal control
      subjects. RESULTS: For hemifield stimuli, the MOBS test procedure had better test
      retest reliability, lower individual variation, and greater separation of the
      normal population and the population with glaucoma than did the MOA procedure.
      The use of progressively smaller, more localized stimuli produced successively
      better separation of glaucomatous and age-matched normal control eyes. Area under
      the Receiver Operating Characteristic curve was 0.81 for hemifield stimuli
      (sensitivity and specificity, 70% to 75%), 0.91 for quadrant stimuli (sensitivity
      and specificity, 83% to 85%), and 0.965 for the 16 stimuli (sensitivity 93%,
      specificity 100%). Test time was approximately 1.3 minutes for hemifields, 1.5
      minutes for quadrants, and 5 minutes for the 16 targets. CONCLUSIONS: Preliminary
      results indicate that the frequency-doubled contrast test provides a quick,
      efficient means of screening for glaucomatous visual field loss. Test time is
      relatively short, test-retest reliability is good, and sensitivity and
      specificity for detection of glaucomatous visual field loss is very good. The use
      of the MOBS staircase procedure and small, localized stimuli result in the best
      performance for screening purposes. An expanded normative database and the use of
      more rapid suprathreshold screening strategies should enhance further the
      efficacy of this test.

PMID- 9040476
TI  - Variability in patients with glaucomatous visual field damage is reduced using
      size V stimuli.
AB  - PURPOSE: To test the hypothesis that variability of conventional automated
      perimetry can be reduced using size V stimuli for patients with glaucomatous
      visual field damage. METHODS: Ten patients with glaucoma and five age-matched
      control volunteers were tested with the Humphrey Field Analyzer program 24-2 or
      30-2, after which the method of constant stimuli was used to measure frequency-of
      seeing curves. This was done by controlling the perimeter with a custom program
      run by a personal computer. At two widely separated visual field locations on the
      program 24-2 or 30-2 grid, stimuli were presented in 2 dB intervals to at least
      10 dB on either side of the estimated program 24-2 or 30-2 threshold. This
      protocol was performed for each of three stimulus sizes (Goldmann sizes I, III,
      and V). For the patients with glaucoma, one test location was chosen in an area
      of normal visual field sensitivity, the other in an area of 10 to 20 dB loss.
      Control subjects were tested at the (3 degrees, 3 degrees) and (-21 degrees, -9
      degrees) test locations. Fifteen repetitions were performed at each intensity.
      RESULTS: Repeated measures analysis of variance showed that variability, as
      measured by the standard deviation of the cumulative Gaussian function of the
      fitted frequency-of-seeing curves, was lowest at the abnormal sensitivity test
      location in the subjects with glaucoma using a size V stimulus. Differences
      between the results from the V to III and V to I stimuli were statistically
      significant (size V = 2.9 dB, III = 10.1 dB, I = 10.1 dB). The same trend in
      estimated standard deviations was present in tests of the area of normal
      sensitivity (size V = 1.1 dB, III = 1.7 dB, I = 2.0 dB) in subjects with glaucoma
      and for the control subjects' peripheral test locations, but not for the central
      location. The smaller reduction in variability between estimated standard
      deviations of the size I and size III stimuli was not statistically significant
      at any test location. CONCLUSIONS: Use of size V stimuli in conventional
      automated perimetry reduces variability in tests of moderately damaged and normal
      sensitivity test locations in subjects with glaucoma.

PMID- 9040477
TI  - Dexamethasone and cyclosporin A modulation of human retinal pigment epithelial
      cell monocyte chemotactic protein-1 and interleukin-8.
AB  - PURPOSE: To examine the modulation of interleukin-1 beta (IL-1 beta)- and tumor
      necrosis factor-alpha (TNF-alpha)-stimulated monocyte chemotactic protein-1 (MCP
      1) and interleukin-8 (IL-8) secretion and transcription in human retinal pigment
      epithelial (HRPE) cells by dexamethasone (DEX) and cyclosporin A (CSA). METHODS:
      Cultured HRPE cells were stimulated with IL-1 beta (0.2 to 20 ng/ml) or TNF-alpha
      (0.2 to 20 ng/ml) for 8 or 24 hours without (control) and with DEX (10(-8) to 10(
      6) M) or with CSA (0.3 to 30 ng/ml). Secreted levels of HRPE MCP-1 and IL-8 were
      measured in the media using enzyme-linked immunosorbent assay (ELISA). Both MCP-1
      and IL-8 mRNA were analyzed by Northern blot. RESULTS: Although DEX (10(-8) to
      10(-6) M) inhibited IL-1 beta-stimulated MCP-1 and IL-8 production, it did not
      inhibit TNF-alpha-stimulated chemokine secretion. In contrast, CSA significantly
      inhibited TNF-alpha-stimulated, but not IL-1 beta-stimulated, HRPE MCP-1 and IL-8
      secretion. Both DEX and CSA inhibitions showed dose dependence. Northern blot
      analysis of HRPE steady state MCP-1 and IL-8 mRNA corroborated the ELISA
      measurements of secreted MCP-1 and IL-8. CONCLUSIONS: Although DEX and CSA
      inhibit HRPE MCP-1 and IL-8 secretion, this is dependent on whether the inducing
      inflammatory mediator is IL-1 beta or TNF-alpha. IL-1 beta-induced chemokine
      secretion is sensitive to DEX, whereas MCP-1 and IL-8 induced by TNF-alpha are
      inhibited by CSA. This information may be useful in explaining in vivo
      observations and in suggesting targeted clinical treatments and combinations of
      immunosuppressive agents.

PMID- 9040478
TI  - Human retinal pigment epithelial cell interleukin-8 and monocyte chemotactic
      protein-1 modulation by T-lymphocyte products.
AB  - PURPOSE: The purpose of the study was to examine the effect of T-lymphocyte
      products on human retinal pigment epithelial (HRPE) cell interleukin-8 (IL-8) and
      monocyte chemotactic protein-1 (MCP-1) secretion and gene expression. METHODS:
      HRPE cells were stimulated for 2, 4, 8, or 24 hours with 20% conditioned media
      (CM) from T-lymphocytes stimulated with CD3 or CD28 monoclonal antibodies (mAbs)
      or phorbol myristic acid. In some experiments, CM from CD3 mAb-stimulated T
      lymphocytes was preincubated with neutralizing anti-(alpha)-tumor necrosis factor
      (TNF), alpha-interferon-gamma (IFN-gamma), or alpha-interleukin-1 (IL-1) mAb
      (control) to determine the contributions of each of these cytokines to HRPE
      chemokine induction by stimulated T-lymphocyte CM. HRPE cells were stimulated for
      8 and 24 hours with IL-1 beta (0.2 to 20.0 ng/ml) (positive control), TNF-alpha
      (0.2 to 20.0 ng/ml) (positive control), IFN-gamma (1 to 1000 U/ml), IFN-gamma +
      IL-1 beta, IFN-gamma + TNF-alpha. Interleukin-2 (IL-2; 100 ng/ml) alone or in
      combination with IL-1 beta, TNF-alpha, or IFN-gamma also was tested. Enzyme
      linked immunosorbent assay (ELISA) and Northern blot analyses were performed to
      determine secreted IL-8 and MCP-1 and their steady state mRNA expression,
      respectively. RESULTS: ELISA showed significant increases in HRPE IL-8 and MCP-1
      secretion by CM from T-lymphocytes stimulated with CD3 or CD3 + CD28 mAb.
      Smaller, but significant, increases in IL-8 and MCP-1 resulted from CM phorbol
      myristic acid-stimulated T-lymphocytes. CM preincubated with neutralizing alpha
      TNF or alpha-IFN-gamma mAb induced significantly less HRPE IL-8 and MCP-1,
      whereas preincubation of CM with neutralizing alpha-IL-1 mAb failed to inhibit CM
      induced IL-8 or MCP-1. Northern blot analysis showed increased HRPE IL-8 and MCP
      1 mRNA expression within 2 hours of stimulation and was maintained up to 24
      hours. CM from T-lymphocytes stimulated with CD3 mAb or CD3 + CD28 mAb produced
      the greatest increases in IL-8 and MCP-1 mRNA. IFN-gamma induced dose-dependent
      increases in HRPE MCP-1, but not IL-8, IFN-gamma potentiated IL-1 beta and TNF
      alpha-induced MCP-1 production, but showed little modulation of IL-1 beta and TNF
      alpha-induced IL-8 production. IL-2 did not induce HRPE IL-8 or MCP-1, nor did it
      modulate the effects of the other cytokines. Northern blot analysis confirmed the
      ELISA results. CONCLUSIONS: T-lymphocyte secretions induce HRPE IL-8 and MCP-1
      gene expression and secretion. TNF and IFN-gamma appear to be necessary
      components of T-lymphocyte CM for the induction of HRPE IL-8 and MCP-1. IFN-gamma
      alone induces HRPE MCP-1, albeit to a lesser extent than would IL-1 beta or TNF
      alpha, and potentiates IL-1 beta- and TNF-alpha-induced HRPE MCP-1. IL-2 does not
      appear to modulate cytokine-induced HRPE IL-8 or MCP-1.

PMID- 9040479
TI  - Tractional force generation by porcine Muller cells. Development and differential
      stimulation by growth factors.
AB  - PURPOSE: To assess the ability of retinal Muller cells to generate tractional
      forces during dedifferentiation in culture and to assess their responsiveness to
      contraction-stimulating growth factors. METHODS: Muller cells were isolated from
      papain-DNase-digested porcine retina. The identity of the isolated cells was
      confirmed by immunodetection of carbonic anhydrase II (CA-II), cellular
      retinaldehyde-binding protein (CRALBP), glial fibrillary acidic protein (GFAP),
      vimentin, and alpha smooth muscle actin (alpha SMA). Tractional force generation
      was assessed as a function of Muller cell contraction of collagenous
      extracellular matrices in vitro. The effects of potential promoters were assessed
      by addition directly to culture medium. The contributions of specific promoting
      to the contraction-promoting activity in serum were assessed by adding
      neutralizing antibodies and measuring loss of stimulatory activity. RESULTS:
      Freshly isolated Muller cells did not generate substantial matrix contraction.
      However, this activity increased 150-fold within 12 days in culture and continued
      to increase during the next 21 days. Development of the capacity for
      extracellular matrix contraction coincided with the acquisition of
      immunodetectable alpha SMA and loss of GFAP. Matrix contraction by Muller cells
      was stimulated in a dose-dependent fashion by human serum, platelet-derived
      growth factor (PDGF), and insulin-like growth factor-I (IGF-I). Muller cells were
      not stimulated by transforming growth factor beta 1 (TGF beta 1), transforming
      growth factor beta 2 (TGF beta 2), or endothelin-1 (E1). Neutralizing antibodies
      against PDGF and IGF-I reduced the activity in human serum by 37% and 58%,
      respectively, and 87% when added together. CONCLUSIONS: Porcine Muller cells in
      culture acquire the ability to contract extracellular matrices and thus generate
      tractional forces. Acquisition of this activity coincides with alpha SMA
      expression and loss of GFAP. Further, this activity is dependent on the presence
      of exogenous promoters, including PDGF or IGF-I.

PMID- 9040480
TI  - Macular function impairment in eyes with early age-related macular degeneration.
AB  - PURPOSE: To study different aspects of macular function in eyes with early age
      related macular degeneration (early AMD: drusen with or without retinal pigment
      epithelium alterations) and normal visual acuity, to obtain a complete evaluation
      of macular function impairment in early AMD and to study the relationship between
      macular function and the ophthalmoscopic signs of early AMD. METHODS: Forty-seven
      subjects with early AMD and visual acuity better than 20/25 in at least one eye
      were studied: 34 patients had bilateral early AMD (group 1), 13 had neovascular
      AMD in the fellow (nonstudy) eye (group 2). Thirty-six age-matched healthy
      subjects were used as controls. Thirty degree stereoscopic fundus photographs and
      fluorescein angiography were performed to grade macular lesions. Macular recovery
      function, central visual field sensitivity, spatiotemporal contrast sensitivity,
      and the Farnsworth-Munsell 100 hue test were used to study different aspects of
      macular function. RESULTS: Except for color vision, all macular function tests
      were significantly impaired in eyes of patients with early AMD compared to those
      in control subjects. No functional difference was found between groups 1 and 2.
      The increase in drusen number negatively influenced macular recovery function.
      Increasing drusen confluence reduced macular recovery function as well as central
      visual field sensitivity and some selected spatial frequencies of spatiotemporal
      contrast sensitivity. Geographic atrophy of the retinal pigment epithelium and
      focal hyperpigmentation reduced macular recovery function and contrast
      sensitivity at the highest spatial frequency. CONCLUSIONS: Macular recovery
      function central visual field sensitivity, and spatiotemporal contrast
      sensitivity are adequate and reliable indicators of macular function impairment
      in early AMD. Macular recovery function is the test that best reflects the
      ophthalmoscopic characteristics of early AMD because its deterioration parallels
      the worsening of typical fundus lesions. Function tests are valuable in the
      evaluation of patients with early AMD, particularly when interventional trials
      are planned.

PMID- 9040481
TI  - Fundus autofluorescence in age-related macular disease imaged with a laser
      scanning ophthalmoscope.
AB  - PURPOSE: To image and quantify the spatial distribution of fundus
      autofluorescence in normal subjects, to determine its age dependence, and to
      document the deviation from normal in patients with age-related macular disease.
      METHODS: Using a confocal laser scanning ophthalmoscope (cLSO), the intensity and
      spatial distribution of fundus autofluorescence was studied in 33 normal
      subjects, 97 eyes with drusen only, and 111 eyes with visual loss caused by age
      related macular disease. RESULTS: Fundus autofluorescence intensity in normal
      subjects was highest at the posterior pole and dipped at the fovea.
      Autofluorescence increased with age at the posterior pole. Fundus in eyes with
      age-related maculopathy showed localized high autofluorescence that did not
      correspond with drusen. Linear pigmentation at the level of the retinal pigment
      epithelium (RPE), whether detached or flat, fluoresced brightly, whereas plaques
      of melanin did not. Areas of low and high levels of autofluorescence were seen in
      lesions containing choroidal new vessels. In areas of geographic atrophy,
      autofluorescence was low. CONCLUSIONS: The spatial distribution of background
      fundus autofluorescence and the correlation of autofluorescence with age in
      normal subjects imply that autofluorescence is derived from lipofuscin at the
      level of the RPE. Focal accumulation of autofluorescent material occurs at the
      level of the RPE in patients with drusen, but the drusen do not show marked
      increases in autofluorescence. It is likely that melanolipofuscin accounts for
      the high levels of autofluorescence, corresponding to linear pigmentation at the
      level of the RPE. Low-intensity autofluorescence occurs in the presence of
      retinal photoreceptor loss, and variable levels over disciform lesions probably
      relate to variations in metabolic activity of the RPE.

PMID- 9040482
TI  - Fusion of intracellular rod outer segment disk membranes with the surrounding
      plasma membrane.
AB  - PURPOSE: The series of experiments described were undertaken to evaluate the use
      of a cell-free lysis model to measure membrane fusion events in photoreceptor rod
      outer segments (ROS). The experiments measure fusion initiated with the osmotic
      disruption of fluorescenty-labeled ROS and correlate these findings with
      previously described disc-plasma membrane fusion. The influence of calcium and
      disc membrane cholesterol content on fusion between ROS membrane species was
      evaluated. METHODS: Membrane fusion was followed by measuring the dilution of a
      membrane-associated fluorophore (R18) from labeled plasma membrane to an
      unlabeled membrane species; discs. Free calcium in the ROS preparations was
      measured using the calcium-sensitive fluorophore Quin-2. The affects of
      cholesterol content on fusion were investigated by increasing and decreasing disc
      membrane cholesterol content using well established lipid exchange techniques.
      RESULTS: There is an increase in R18 fluorescence on hypotonic lysis of ROS whose
      plasma membrane is labeled with R18. This increase in fluorescence is inhibited
      by EGTA and requires nanomolar levels of calcium. The initial rates of fusion
      between R18-labeled plasma membrane and discs were virtually identical in discs
      with increased and decreased levels of membrane cholesterol. CONCLUSIONS: The
      increase in R18 fluorescence on lysis of R18-labeled ROS is consistent with
      fusion between disc membranes and the surrounding plasma membrane. This fusion is
      dependent on nanomolar levels of calcium, is inhibited by EGTA, and is
      independent of the cholesterol content of these membranes.

PMID- 9040483
TI  - Generation and analysis of transgenic mice expressing P216L-substituted
      rds/peripherin in rod photoreceptors.
AB  - PURPOSE: In this study, the authors present the biochemical, morphologic, and
      physiological analyses of a transgenic mouse model for retinal degeneration slow
      (RDS)-mediated retinitis pigmentosa caused by a proline 216 to leucine (P216L)
      amino acid substitution in rds/peripherin. METHODS: The authors assembled a
      mutant rds transgene that encodes rds/peripherin with a P216L substitution.
      Transgenic mice were generated on wild-type (+/+), heterozygous (rds-/+), and
      homozygous (rds-/rds-) null genetic backgrounds. These mice were analyzed
      biochemically, by light and electron microscopy, and by electroretinography.
      RESULTS: In P216L-transgenic mice on a +/- background, the authors observed
      expression-level-dependent photoreceptor degeneration and outer-segment
      shortening. Expression of the P216L transgene on an rds-/+ background resulted in
      more severe photoreceptor degeneration and outer-segment dysplasia than seen in
      nontransgenic rds-/+ mutants. Severely dysplastic outer segments were detectable
      in P216L transgenics on an rds-/rds-null background. The reduction in b-wave
      amplitudes by electroretinography were well correlated with the degree of
      photoreceptor degeneration, but not outer-segment dysplasia in these different
      rds mutants. CONCLUSIONS: The phenotype in P216L-transgenic mice on an rds-/+
      genetic background probably is caused by a combination of two genetic mechanisms:
      a direct dominant effect of the P216L substituted protein, and a reduction in the
      level of normal rds/peripherin. The expression pattern of the normal and mutant
      genes in these animals is similar to that predicted for humans with RDS-mediated
      autosomal-dominant retinitis pigmentosa. These mice may thus be considered an
      animal model for this disease.

PMID- 9040484
TI  - Pharmacologic evidence for 5-HT1A receptors associated with human retinal pigment
      epithelial cells in culture.
AB  - PURPOSE: The authors investigate the possible presence of 5-hydroxytryptamine (5
      HT1) type serotonin receptors negatively coupled to adenylate cyclase activity in
      cultured human retinal pigment epithelial (RPE) cells. METHODS: Adenylate cyclase
      activity was assessed by the determination of cellular adenosine 3':5' cyclic
      monophosphate (cAMP) levels and the effects of serotonin on both basal and
      forskolin-stimulated cAMP levels studied. RESULTS: Serotonin at 100 microM had no
      effect on the basal levels of cAMP in cultured human RPE cells, but attenuated by
      43.6% the stimulation in cAMP production induced by forskolin (5 microM). This
      effect was dose dependent for serotonin with half-maximal inhibition (EC50)
      occurring at approximately 1.5 x 10(-9) M. The 5-HT1 receptor agonist 8-hydroxy
      [2-di-n-propylamino] tetralin (8-OH DPAT), buspirone, 5-carboxyamidotryptamine,
      and RU24969 mimicked the inhibitory effect of serotonin in a dose-dependent
      manner. The actions of serotonin and 8-OH DPAT (10 microM) were dose-dependently
      attenuated by the serotonergic antagonists spiroxatrine, propranolol, and
      spiperone. Pretreatment of RPE cell cultures with pertussis toxin abolished the
      serotonin-induced reduction of forskolin-elevated cAMP levels. Stimulation of
      cAMP production by the beta-adrenoceptor agonist isoproterenol at 0.1 microM, but
      not at 10 microM or 100 microM, also was attenuated by serotonin (100 microM),
      whereas cAMP production induced by the adenosine receptor agonist 5'-[N-ethyl]
      carboxamidoadenosine (NECA) at 1 microM, 10 microM, and 100 microM was
      unaffected. Serotonin and 8-OH DPAT dose-dependently inhibited isoproterenol
      stimulated (0.1 microM) cAMP production with EC50 values of approximately 10
      microM, and pertussis toxin pretreatment partially blocked these effects.
      CONCLUSIONS: Cultured human RPE cells possess 5-HT1A receptors negatively coupled
      to cAMP production through a pertussis toxin-sensitive G protein. These receptors
      show differential effects on forskolin-, isoproterenol-, and NECA-stimulated cAMP
      production, which may reflect a unique spatial distribution of receptor proteins
      or the phenotypic heterogeneity of RPE cells that is the result of or that is
      preserved in culture.

PMID- 9040485
TI  - cis-Hydroxyproline inhibits proliferation, collagen synthesis, attachment, and
      migration of cultured bovine retinal pigment epithelial cells.
AB  - PURPOSE: Proliferative vitreoretinopathy (PVR) is characterized by the
      proliferation and migration of retinal pigment epithelial (RPE) and other cells
      into the vitreous cavity. The PVR membrane formation also is associated with
      collagen production by RPE. The authors examined the effect of a proline analog,
      cis-hydroxyproline (CHP), on proliferation, collagen synthesis, attachment, and
      migration of bovine RPE in vitro. METHODS: The effect of CHP on cell
      proliferation was determined as a function of dosage and days in culture by
      counting the cell numbers on days 3, 6, and 9. Collagen synthesis was determined
      by trichloroacetic acid precipitation of the radiolabeled samples before and
      after bacterial collagenase digestion. The attachment assay involved type I
      collagen or fibronectin substrates or both (2.5 micrograms/well). For migration
      experiments, RPE cells were removed from a defined area of a confluent culture,
      and migration was quantitated by counting the number of cells migrating into the
      denuded area over 30 hours. RESULTS: The addition of CHP inhibited RPE
      proliferation in both a dose- and a time-dependent manner; collagen synthesis,
      attachment, and migration also were inhibited by CHP in a dose-dependent manner.
      When the culture plates were coated with collagen, < 100 micrograms/ml of CHP had
      no effect on cell attachment. Higher doses of CHP resulted in mild inhibition of
      attachment on collagen-coated plates. Simultaneous addition of L-proline to the
      cultures resulted in blockade of these inhibitory effects on proliferation,
      collagen synthesis, attachment, and migration. CONCLUSIONS: The results show that
      RPE functions critical to the development of PVR are inhibited by CHP, suggesting
      the possibility that this drug may have potential clinical application.

PMID- 9040486
TI  - Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA
      levels in keratoconus corneas.
AB  - PURPOSE: Keratoconus is characterized by thinning and scarring of the central
      region of the cornea. The authors have shown, in corneas obtained from patients
      with keratoconus, that lysosomal enzyme activities are elevated, whereas levels
      of protease inhibitors such as alpha 1-proteinase inhibitor (alpha 1-PI) are
      reduced. This study was undertaken to examine further the gene expression of
      cathepsin G, acid phosphatase, and alpha 1-PI in keratoconus corneas. METHODS:
      Corneal buttons were collected from patients with keratoconus, normal subjects,
      and patients with other corneal diseases. In situ hybridization was performed on
      paraffin sections using a tritium-labeled probe for cathepsin G or alpha 1-PI.
      Competitive polymerase chain reaction (PCR) was used to determine the messenger
      RNA (mRNA) levels for lysosomal acid phosphatase and alpha 1-PI in epithelial and
      stromal cells of keratoconus corneas. RESULTS: Silver grains, indicative of
      positive in situ hybridization products, were observed in all three cell types of
      normal corneas for both DNA probes. Compared with normal and other diseased
      controls, the labeling was enhanced for cathepsin G but was diminished for alpha
      1-PI in the epithelium of keratoconus corneas. Competitive PCR showed that the
      mRNA level for acid phosphatase was higher and that the mRNA level for alpha 1-PI
      was lower in keratoconus corneas. CONCLUSIONS: These results indicate that the
      mRNA level for degradative enzymes in increased and that for alpha 1-PI it is
      reduced in keratoconus corneas. This study provides the first evidence that the
      altered expression of multiple enzymes and inhibitors in keratoconus occurs at
      the gene level. Furthermore, it implicates a possible role of coordinated
      transcriptional regulation of gene expressions in keratoconus.

PMID- 9040487
TI  - The antigen-bearing eye and the spleen are indispensable in maintaining anterior
      chamber-associated immune deviation.
AB  - PURPOSE: To investigate the role of the eye and the spleen in maintaining
      suppression of delayed-type hypersensitivity (DTH) after anterior chamber (AC)
      inoculation of allogeneic splenocytes. METHODS: Suppression of DTH response was
      tested in BALB/c mice after AC inoculation of allogeneic B10.D2 splenocytes.
      Seven days after AC injection, the antigen-inoculated eyes were enucleated or the
      spleens were removed. After enculeation or splenectomy at different time
      intervals, DTH responses in groups of the BALB/c mice were examined. Spleen
      components obtained from BALB/c mice that had been primed by B10.D2 splenocytes
      in the AC 7 days earlier were transferred intravenously to groups of naive
      syngeneic acceptors. At various intervals after adoptive transfer, variations of
      DTH responses were tested. RESULTS: Inoculation of B10.D2 splenocytes to the AC
      of BALB/c mice induced antigen-specific suppression of DTH. Either enucleation of
      the antigen-inoculated eyes or splenectomy weakened the DTH-suppressive effect
      within 5 weeks and abolished it within 9 weeks, whereas the mice retaining both
      antigen-inoculated eyes and spleens maintained longstanding DTH suppression.
      Adoptive transfer of spleen components to syngeneic acceptors demonstrated DTH
      suppression for only 3 weeks. CONCLUSIONS: The antigen-inoculated eye and spleen
      are required for long-standing suppression of DTH after AC inoculation of
      allogeneic splenocytes.

PMID- 9040488
TI  - Expression of carbonic anhydrase isozyme III in the ciliary processes and lens.
AB  - PURPOSE: To determine whether carbonic anhydrase isozyme (CA) III is expressed in
      the ciliary processes and lens. METHODS: Total RNA was isolated from rabbit
      ciliary epithelium and human ciliary processes and from the anterior lens of
      rabbit, cow, and human eyes. First-strand cDNA was synthesized, and the
      polymerase chain reaction (PCR) was performed using oligomer primers designed to
      amplify CA III sequences specifically. Selected PCR products were eluted from
      agarose gels, cloned, and sequenced. Northern blots were performed to confirm the
      presence of CA III in these tissues. RESULTS: Polymerase chain reaction products
      of the predicted size were generated from rabbit ciliary epithelium and from
      rabbit, bovine, and human lens. The sequence of the PCR product from human lens
      was identical to the published sequence of the corresponding region of the human
      CA III gene. The sequence of the PCR products from rabbit ciliary epithelium and
      bovine lens showed 88% and 97% identity, respectively, with the corresponding
      sequences for human CA III, suggesting that the PCR products corresponded to the
      rabbit and bovine orthologs. Northern blots confirmed the presence of CA III mRNA
      in the rabbit ciliary epithelium and in rabbit and bovine lens. CONCLUSIONS: mRNA
      for CA III is present in the intraocular tissues of rabbits, cows, and humans.
      The previous detection of CA III protein in the bovine lens is confirmed, and it
      extended to the lenses of other species, including humans. The detection of mRNA
      for CA III in the ciliary epithelium is new and suggests that the ciliary
      epithelium contains not only isozymes II and IV but isoenzyme III as well.
      Although the function of CA III in the eye is unknown, it may play a role in
      fluid transport and homeostasis.

PMID- 9040489
TI  - Reattachment of extraocular muscles using fibrin glue in a rabbit model.
AB  - PURPOSE: Reattaching extraocular muscles by the conventional suturing method may
      be complicated by scleral perforation. The attachment of extraocular muscles,
      using fibrin sealants, avoids such risk. The authors evaluated the use of fibrin
      sealant in a laboratory rabbit model. METHODS: Fifty-eight eyes of 29 rabbits
      were used in the study. In both eyes of each rabbit, the superior rectus muscle
      was disinserted, recessed, and either sutured or reattached to the globe by
      fibrin sealant. Two groups of eyes were compared. In one group (42 eyes), the
      recessed muscle was reattached using fibrin sealant. In the second group (16
      eyes), sutures were used to reattach the recessed muscle to the globe. The
      insertion of the superior rectus muscle was examined 14 days after surgery, and
      histopathologic evaluation was performed 6 weeks after the surgery. RESULTS:
      Although in the sutured muscle group no slippage from the original placement was
      found, it was found in the group in which fibrin glue was used. The muscle
      slippage was greater at the small muscle recessions and smaller at the large
      muscle recessions. For muscle recession of 6 mm or more, the average muscle
      slippage was 0.12 +/- 0.28 mm, which was not statistically different from the
      suture group (P = 0.0828). CONCLUSIONS: Fibrin sealant was found to be effective
      for extraocular muscle reattachment only in large muscle recessions. However, in
      small muscle recessions the glue was not strong enough to overcome the
      contractive strength of the muscle.

PMID- 9040490
TI  - Regulation of paracrine cytokine balance controlling collagenase synthesis by
      corneal cells.
AB  - PURPOSE: Classic studies have demonstrated that corneal epithelial cell density
      in culture can alter the balance of stimulatory and inhibitory cytokines
      controlling the elaboration of collagenolytic activity by co-cultured stromal
      cells. The current study attempts to bring the understanding of this mechanism to
      a molecular level. METHODS: A rabbit primary corneal cell culture model was used.
      RESULTS: Using molecular probes that bind to and neutralize specific cytokines, a
      major stimulator for stromal cell collagenase synthesis released by corneal
      epithelial cells into culture medium was identified as interleukin-1 alpha (IL-1
      alpha), and a secondary stimulator was characterized as a heparin-binding
      cytokine. An inverse relationship between net collagenase stimulatory activity
      and epithelial cell plating density was demonstrated. In contrast, the release of
      inhibitory activity for IL-1-stimulated collagenase synthesis was not subject to
      the cell density effect. Direct measurement of IL-1 alpha protein levels revealed
      that this cytokine was released much more efficiently on a per cell basis when
      cells were plated at low density than when they were plated at high density. The
      effect was not caused by greater cell lysis at low cell density and was mediated
      only partially by changes at the IL-1 alpha synthesis level. CONCLUSIONS: These
      data provide evidence that epithelial cells release stimulatory cytokines for
      collagenase expression more efficiently when they have limited contact with their
      neighbors and that this has important consequences for the overall paracrine
      cytokine balance controlling collagenase synthesis. Alteration of the paracrine
      cytokine balance by changes in cell contact may be an important means for
      regulating epithelial-stromal interactions involved in corneal development and
      repair.

PMID- 9040491
TI  - A new rat model of thrombotic focal cerebral ischemia.
AB  - We developed a fibrin-rich thrombotic focal cerebral ischemic model with
      reproducible and predictable infarct volume in rats. In male Wistar rats (n =
      77), a thrombus was induced at the origin of the middle cerebral artery (MCA) by
      injection of thrombin via an intraluminal catheter placed in the intracranial
      segment of the internal carotid artery (ICA). Thrombus induction and consequent
      ischemic cell damage were examined by histopathological analysis and neurological
      deficit scoring, and by measuring changes in cerebral blood flow (CBF) using
      laser-Doppler flowmetery (LDF), perfusion-weighted imaging (PWI), and by
      diffusion weighted imaging (DWI). Histopathology revealed that a fibrin-rich
      thrombus localized to the origin of the right MCA. Regional cerebral blood flow
      (rCBF) in the right parietal cortex was reduced by 34-58% of preinjection levels
      after injection of thrombin in rats administered 30 U of thrombin (n = 10).
      Magnetic resonance imaging (MRI) showed a reduction in CBF and a hyperintensity
      DWI encompassing the territory supplied by the right MCA. The infarct volume in
      rats administered 80 U of thrombin was 31.29 +/- 12.9% of the contralateral
      hemisphere at 24 h (n = 13), and 34.7 +/- 16.4% of the contralateral hemisphere
      at 168 h (n = 6). Rats administered 30 U of thrombin exhibited a hemispheric
      infarct volume of 34.0 +/- 14.5% (n = 9) at 24 h and 29.7 +/- 13.9% (n = 8) at
      168 h. In addition, thrombotic rats (n = 3) treated with recombinant tissue
      plasminogen activator (rt-PA) (10 mg/kg) 2 h after thrombosis showed that CBF
      rapidly returned towards preischemic values as measured by PWI. This model of
      thrombotic ischemia is relevant to thromboembolic stroke in humans and may be
      useful in documenting the safety and efficacy of thrombolytic intervention as
      well as for investigating therapies complementary to antithrombotic therapy.

PMID- 9040492
TI  - Chronic nicotine treatment enhances focal ischemic brain injury and depletes free
      pool of brain microvascular tissue plasminogen activator in rats.
AB  - Effects of nicotine treatment (4.5 mg/kg of nicotine-free base/day administered
      s.c. by osmotic minipumps for 14 days) on focal ischemic stroke and expression of
      tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)
      in cerebral microvessels were studied in rats in vivo using a reversible (1 h)
      middle cerebral artery occlusion model. Plasma levels of nicotine and its major
      metabolite cotinine after 14 days of treatment were 88 and 364 ng/ml,
      respectively. Nicotine treatment resulted in 35-40% (p < 0.001) decrease in the
      blood flow in the periphery of the ischemic core during reperfusion, an increase
      in the neurologic score of 2.6-fold (p < 0.01), and 36% (p < 0.05) and 121% (p <
      0.01) increases in the injury and edema volume in the pallium, respectively. A
      free pool of brain microvascular t-PA antigen was completely depleted by
      nicotine, while the expression of the PAI-1 antigen and/or PAI-1-t-PA complexes
      remained unchanged. The relative abundance of cerebromicrovascular t-PA mRNA
      transcript versus beta-actin mRNA transcript did not change with nicotine. It is
      concluded that chronic nicotine treatment impairs the restoration of blood flow,
      worsens the neurologic outcome, and enhances brain injury following an ischemic
      insult. These nicotine effects are associated with depletion of brain
      microvascular t-PA antigen.

PMID- 9040493
TI  - Effects of the AMPA-receptor antagonist, NBQX, on neuron loss in dentate hilus of
      the hippocampal formation after 8, 10, or 12 min of cerebral ischemia in the rat.
AB  - The alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor antagonist, 2,3
      dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), offers protection to
      hippocampal CA1 pyramidal cells after short episodes of transient cerebral
      ischemia. Besides CA1 pyramidal cells, neurons containing somatostatin (SS) and
      located in the dentate hilus of the hippocampal formation are lost after cerebral
      ischemia. We studied the protective effects of NBQX on SS neurons in the hilus
      and on hippocampal CA1 pyramidal cells following 8, 10, or 12 min of four-vessel
      occlusion ischemia during systemic hypotension. NBQX was administered 3 x 30
      mg/kg at 0, 10, and 25 after induction of ischemia or sham, and all rats survived
      for 7 days. NBQX given to control rats without ischemia had no influence on
      number or morphology of hilar SS neurons and CA1 pyramidal cells. After 8 min of
      ischemia, NBQX prevented loss of hilar SS neurons. After 10 and 12 min of
      ischemia, NBQX had no significant effects on loss of SS neurons in the dentate
      hilus. However, in all ischemic groups, NBQX significantly reduced loss of CA1
      pyramidal cells as compared to control rats. This neuroprotective effect
      decreased gradually and significantly as the time of ischemia increased. Our
      results support the observation that SS neurons in hilus are among the most
      ischemia-vulnerable neurons in the brain. We found that administration of NBQX in
      generally accepted dosages can protect the rapidly dying SS neurons in hilus from
      only brief episodes of ischemia.

PMID- 9040495
TI  - Neuroprotective effect of NMDA receptor glycine recognition site antagonism
      persists when brain temperature is controlled.
AB  - Several lines of inquiry have indicated that glycine plays an important role in
      both glutamatergic neurotransmission and pathophysiology of cerebral ischemia.
      However, subacute outcome trials demonstrating the efficacy of glycine
      antagonists as neuroprotectants have not been performed with rigorous control of
      brain temperature. In this study, we investigated the effect of N-methyl-D
      aspartate (NMDA) receptor glycine recognition site antagonism in a temperature
      controlled rodent model of transient focal ischemia. Male Wistar rats underwent
      75 min of intraluminal middle cerebral artery occlusion (MCAO). During MCAO and
      the first 24 h of reperfusion, rats (n = 10) were administered e55-nitro-6,7
      dichloro-2,3-quinoxalinedione (ACEA 1021) i.v. as a bolus infusion of 5 mg/kg
      followed by 3.5 mg/kg/h (Low-Dose) or 10 mg/kg followed by 7 mg/kg/ h (High-Dose)
      for 24 h. Cortical temperature was controlled at 38.0 +/- 0.1 degrees C during
      MCAO and the first 6 h of reperfusion. A 7-day recovery interval was allowed.
      Mean total infarct volume was reduced by approximately 40% in both high- and low
      dose groups (p < 0.01). The preponderance of infarct reduction occurred in the
      cortex (p < 0.01). Neurologic function correlated with the size of cerebral
      infarct (p = 0.001). Neurologic grade was similarly improved by treatment with
      either dose (p = 0.01). These results demonstrate that neuroprotection achieved
      by antagonism of the glycine recognition site persists when brain temperature is
      controlled, indicating a potent mechanism of action other than attenuating a
      hyperthermic response to ischemia.

PMID- 9040494
TI  - Characterization of metabotropic glutamate receptor-mediated nitric oxide
      production in vivo.
AB  - We tested the hypothesis that stimulation of metabotropic glutamate receptors
      (mGluRs) increases nitric oxide (NO) production in the hippocampus in vivo.
      Microdialysis probes were placed bilaterally into the CA3 region of the
      hippocampus of adult Sprague-Dawley rats under pentobarbital anesthesia. Probes
      were perfused for 5 h with artificial cerebrospinal fluid (CSF) containing 3
      microM [14C]-L-arginine. Recovery of [14C]-L-citrulline in the effluent was used
      as a marker of NO production. In nine groups of rats, increases in [14C]-L
      citrulline recovery were compared between right- and left-sided probes perfused
      with various combinations of the selective mGluR agonist, trans-(1S,3R)-1-amino
      1,3-cyclopentanedicarboxylic acid (ACPD); the mGluR antagonist, (+/-)-alpha
      methyl-4-carboxyphenylglycine (MCPG); the NO synthase inhibitor, N-nitro-L
      arginine (LNNA); the ryanodine sensitive calcium-release channel inhibitor
      dantrolene, the non-N-methyl-D-aspartate (NMDA); receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX); the NMDA receptor antagonist (+)-5-methyl
      10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801); and the Na+
      channel blocker, tetrodotoxin. Recovery of [14C]-L-citrulline during perfusion
      with artificial CSF progressively increased to 90 +/- 21 fmol/min (+/-SD) over 5
      h. Perfusion in the contralateral hippocampus with 1 mM ACPD augmented [14C]-L
      citrulline recovery to 250 +/- 81 fmol/min. Perfusion of 1 mM nitroarginine +
      ACPD inhibited [14C]-L-citrulline recovery compared to that with ACPD alone.
      Perfusion with 1 mM MCPG + ACPD attenuated ACPD enhanced [14C]-L-citrulline
      recovery. Perfusion of 1 mM dantrolene + ACPD inhibited the ACPD-evoked increase
      in [14C]-L-citrulline recovery. Perfusion of 1 mM MCPG or dantrolene without ACPD
      did not decrease [14C]-L-citrulline recovery as compared to CSF alone. ACPD
      enhanced [14C]-L-citrulline recovery was not attenuated by CNQX, MK-801, or
      tetrodotoxin (TTX). Using an indirect method of assessing NO production in vivo,
      these data demonstrate that mGluR stimulation enhances NO production in rat
      hippocampus. Inhibition with dantrolene suggests that calcium-induced calcium
      release amplifies the inositol triphosphate-mediated calcium signal associated
      with mGluR stimulation, thereby resulting in augmented calcium-dependent NO
      production.

PMID- 9040496
TI  - Isoflurane and propofol block neurotoxicity caused by MK-801 in the rat posterior
      cingulate/retrosplenial cortex.
AB  - In acute brain injury syndromes, the potent N-methyl-D-aspartate (NMDA)
      antagonist, MK-801, can prevent neuronal degeneration, and the general
      anesthetics, isoflurane and propofol, may also provide neuroprotective benefits.
      An obstacle to the use of NMDA antagonists for neuroprotective purposes is that
      they can cause a neurotoxic vacuole reaction in cerebrocortical neurons. This
      study demonstrates the ability of isoflurane and propofol to prevent the
      neurotoxic vacuole reaction induced by MK-801. Low sedative doses of inhaled
      isoflurane (1%) or intravenous (i.v.) propofol (7.5 mg/kg/h) were as effective as
      higher general anesthetic doses. Thus, in the clinical management of acute brain
      injury conditions such as stroke and brain trauma, administration of one of these
      anesthetic agents together with an NMDA antagonist may be an excellent formula
      for obtaining optimal neuroprotection while eliminating serious side effects.

PMID- 9040497
TI  - Rapid preconditioning protects rats against ischemic neuronal damage after 3 but
      not 7 days of reperfusion following global cerebral ischemia.
AB  - Earlier studies indicated that sublethal ischemic insults separated by many hours
      may "precondition" and, thereby, protect tissues from subsequent insults. In
      Wistar rats, we examined the hypothesis tht ischemic preconditioning (IPC) can
      improve histopathological outcome even if the "conditioning" and "test" ischemic
      insults are separated by only 30 min. Normothermic (36.5-37 degrees C) global
      cerebral ischemia was produced by bilateral carotid artery ligation after
      lowering mean systemic blood pressure. The conditioning ischemic insult lasted 2
      min and was associated with a time sufficient to provoke "anoxic depolarization"
      (AD) (i.e., the abrupt maximal increase in extracellular potassium ion activity).
      After 30 min of reperfusion, 10-min test ischemia was produced, and
      histopathology was assessed 3 and 7 days later. After 3 days of reperfusion,
      neuroprotection was most robust in the left lateral, middle and medial
      subsections of the hippocampal CA1 subfield and in the cortex, where protection
      was 91, 76, 70 and 86%, respectively. IPC also protected the right lateral,
      middle and medial subsections of the hippocampal CA1 region. These data
      demonstrate that neuroprotection against acute neuronal injury can be achieved by
      conditioning insults followed by only short (30 min) periods of reperfusion.
      However, neuroprotection almost disappeared when reperfusion was continued for 7
      days. When test ischemia was decreased to 7 min, a clear trend of neuroprotection
      by IPC was observed. These data suggest that subsequent rescue of neuronal
      populations could be achieved with better understanding of the neuroprotective
      mechanisms involved in this rapid IPC model.

PMID- 9040498
TI  - MRI measurements of water diffusion and cerebral perfusion: their relationship in
      a rat model of focal cerebral ischemia.
AB  - The aim of this study was to examine the quantitative relationship between
      changes in apparent diffusion coefficient (ADC) and transverse relaxivity (delta
      R2*) measurements of relative perfusion deficits within the gradients of a focal
      ischemic insult. Sixty minutes after permanent occlusion of the middle cerebral
      artery, rats (n = 7) were subjected to spin echo diffusion-weighted scans
      followed by fast low-angle shot (FLASH) perfusion-sensitive scans. Diffusion
      weighted images showed clear ischemic lesions in the affected basal ganglia and
      cortex. Ischemic deficits were demonstrated as a decrease in first-pass transit
      of injected boluses of gadodiamide. ADC maps were generated and regions of
      interest (ROIs) were obtained to span the range of ADC reductions from the lesion
      center or core to the periphery or penumbra. Corresponding ROIs from the bolus
      injection images were used to calculate perfusion indexes relative to
      contralateral levels as ratios of delta R2* integrals and ratios of delta R2*
      peak values. In all animals, the degree of ADC reductions was related to the
      degree of delta R2* perfusion deficits, ranging from severe ischemia in the core
      of the lesion to intermediate and moderate changes toward the lesion periphery.
      In the ischemic periphery, ADC reductions were linearly correlated with delta R2*
      peak ratios. However, no significant correlation was found between ADC reductions
      and delta R2* integral ratios. These data suggest that magnetic resonance
      measurements of ADC and delta R2* peak ratios can be used to quantitatively
      assess the variable gradients in focal ischemia, including potentiallyn critical
      areas at risk in the ischemic periphery.

PMID- 9040499
TI  - Ischemia-induced changes in the extracellular space diffusion parameters, K+, and
      pH in the developing rat cortex and corpus callosum.
AB  - Changes in the ability of substances to diffuse in the intersticial space of the
      brain are important factors in the pathophysiology of cerebrovascular diseases.
      Extracellular space (ECS) volume fraction alpha (alpha = ECS volume/ total tissue
      volume), tortuosity lambda (lambda 2 = free diffusion coefficient/apparent
      diffusion coefficient), and nonspecific uptake (k')-three diffusion parameters of
      brain tissue were studied in cortex and subcortical white matter (WM) of the
      developing rat during anoxia. Changes were compared with the rise in
      extracellular potassium concentration ([K+]e), extracellular pH (pHe) shifts, and
      anoxic depolarization (AD). Diffusion parameters were determined from
      extracellular concentration-time profiles of tetramethylammonium (TMA+) or
      tetraethylammonium (TEA+), TMA+, TEA+, K+, and pH changes were measured using ion
      selective microelectrodes. In the cortex and WM of animals at 4-12 postnatal days
      (P4-P12), the volume fraction, alpha, is larger than that of animals at > or =
      P21. Anoxia evoked by cardiac arrest brought about a typical rise in [K+]e to
      approximately 60-70 mM, AD of 25-30 mV, decrease in alpha, increase in lambda,
      and increase in k'. At P4-P6, alpha decreased from approximately 0.43 to 0.05 in
      cortical layer V and from approximately 0.45 to 0.5 in WM. Tortuosity, lambda,
      increased in the cortex from 1.50 to 2.12 and in WM from approximately 1.48 to
      2.08. At P10-P12 and at P21-P23, when alpha in normoxic rats is lower than at P4
      P6 by approximately 25 and 50%, respectively, the final changes in values of
      alpha and lambda evoked by anoxia were not significantly different from those in
      P4-P6. However, the younger the animal, the longer the time course of the
      changes. On P4-P6 final changes in alpha, lambda and k' in cortex and WM were
      reached after 37 +/- 3 min and 54 +/- 2 min; on P10-P12, after 24 +/- 2 and 27 +/
      3 min; and on P21-P23 at 15 +/- 1 and 17 +/- 3 min, respectively (mean +/- SE, n
      = 6). The time course of the changes was longer in WM than in gray matter (GM),
      particularly during the first postnatal week, i.e., in the period during which WM
      is largely unmyelinated. Changes in diffusion parameters occurred in three
      phases. The first slow and second fast changes occurred simultaneously with the
      rise in [K+]e and AD. Peaks in [K+]e and AD were reached simultaneously; the
      younger the animal, the longer the time course of the changes. The third phase
      outlasted the rise in [K+]e and AD by 10-15 min and correlated with the acid
      shift in pHe. Linear regression analysis revealed a positive correlation between
      the normoxic size of the ECS volume and the time course of the changes. Slower
      changes in ECS volume fraction and tortuosity in nervous tissue during
      development can contribute to slower impairment of signal transmission, e.g., due
      to lower accumulation of ions and neuroactive substances released from cells and
      their better diffusion from the hypoxic area in uncompacted ECS.

PMID- 9040500
TI  - Distribution of Glut1 glucose transporters in different brain structures compared
      to glucose utilization and capillary density of adult rat brains.
AB  - Glut1 is a specific transporter system that mediates glucose transfer across the
      blood-brain barrier (BBB). Although the main location of Glut1 is in the
      capillary endothelium of the brain, its local distribution in different brain
      regions is not as well defined. In the present investigation, the local pattern
      of Glut1 distribution was determined in 13 brain structures using an
      immunoautoradiographic method developed for this purpose. A polyclonal antibody
      directed against the C-terminal amino acid sequence of Glut1 was applied to
      cryosections of rat brains. A secondary antibody was added that had been coupled
      to [35S]. Results show a heterogeneous distribution of Glut1 in the brain with
      activities of [35S] ranging from 65% below to 15% above the mean. White matter
      activity was lower than gray matter activity. For comparison, capillary sections
      were counted in corresponding cryosections by indirect immunofluorescence using
      fibronectin antibodies. In addition, local cerebral glucose utilization (LCGU)
      was analyzed in identical brain structures of conscious rats by the quantitative
      autoradiographic 2-deoxyglucose method. Significant correlations were found
      between Glut1 density and either LCGU or capillary density. Results indicate a
      tight coupling of Glut1 transporter density and capillary density to the LCGU of
      different BBB structures in adult rats.

PMID- 9040501
TI  - Identification, characterization, and functional role of phosphodiesterase type
      IV in cerebral vessels: effects of selective phosphodiesterase inhibitors.
AB  - The role of the phosphodiesterase type IV isozyme (PDE IV) in the regulation of
      cerebrovascular tone was investigated in the canine basilar artery in vitro and
      in vivo. The PDE isozymes extracted from the canine basilar artery were isolated
      by diethylaminoethanol (DEAE)-Sepharose affinity chromatography and identified
      based on sensitivity to isozyme-selective PDE inhibitors. [3H]cAMP hydrolysis was
      observed in one major and one minor peak of activity. The predominant peak was
      inhibited by the addition of cGMP (25%), siguazodan (26%), rolipram (39%), and
      the combination of siguazodan and rolipram (95%). Selective PDE IV inhibitors BRL
      61063, rolipram, and denbufylline were equieffective inhibitors of [3H]-ccAMP
      hydrolysis mediated by PDE IV isolated from the canine basilar artery
      [concentrations producing 50% inhibition (IC50S) = 0.21 +/- 0.05 microM, 0.67 +/-
      0.23 microM, and 0.73 +/- 0.16 microM, respectively]. In precontracted isolated
      ring segments of the canine basilar artery, selective PDE IV inhibitors produced
      potent and complete relaxation (IC50S < 150 nM). In contrast, zaprinast (a
      selective PDE V inhibitor) and siguazodan (a selective PDE III inhibitor)
      produced only weak relaxation of the basilar artery (IC50S = 4.5 microM and > 10
      microM, respectively). Vasorelaxation produced by PDE IV inhibitors was not
      altered by removing the endothelium, 1-NAME, or adenosine receptor antagonism. In
      a canine model of acute cerebral vasospasm, all three selective PDE IV inhibitors
      reversed basilar artery spasm produced by autologous blood without altering mean
      arterial blood pressure. In contrast, prolonged treatment with BRL 61063 failed
      to alter the development of basilar spasm in the two hemorrhage canine models of
      chronic cerebral vasospasm. Denbufylline-induced relaxation in vitro was also
      significantly impaired in basilar arteries obtained from the model of chronic
      vasospasm. In conclusion, PDE IV appears to be the predominant isozyme regulating
      vascular tone mediated by cAMP hydrolysis in cerebral vessels. In addition,
      vasorelaxation modulated by PDE IV is compromised in chronic cerebral vasospasm
      associated with subarachnoid hemorrhage.

PMID- 9040502
TI  - Physostigmine reversal of scopolamine-induced hypofrontality.
AB  - The muscarinic receptor antagonist scopolamine produces a transient memory
      deficit in healthy humans. This deficit has been offered as a model of the
      cholinergic deficit of Alzheimer's disease (AD). However, we have previously
      shown that scopolamine produces a deficit of cortical perfusion maximal in the
      frontal lobe, dissimilar to the parietal cortex deficit characteristic of AD. The
      current experiment was aimed at replicating and extending this observation by
      critically testing the central cholinergic origin of both cognitive and perfusion
      deficits. Nine healthy subjects participated in regional cerebral blood flow
      (rCBF) measurements at baseline, after scopolamine (7.2 micrograms/kg i.v.), and
      after both physostigmine (22 micrograms/kg i.v.) and neostigmine (7 or 11
      micrograms/kg i.v.). rCBF was quantified by the xenon 133 inhalation method. As
      expected, scopolamine reduced cortical perfusion, mainly in the frontal cortex,
      and produced a memory deficit. Physostigmine, but not neostigmine, reversed all
      three variables partially or completely. These results support the hypothesis
      that all three consequences of scopolamine, namely, reduction of mean flow,
      frontal deficit, and memory impairment, are cholinergically mediated.
      Furthermore, because neostigmine poorly crosses the blood-brain barrier, these
      findings confirm that the effect is centrally mediated and cannot be explained by
      peripheral effects. However, they also confirm the frontal cortex locus of action
      for both scopolamine and its reversal by physostigmine and therefore suggest a
      major dissimilarity to the characteristic rCBF appearance of AD. This study
      extends our previous preliminary findings with tacrine and strengthens the
      suggestion that only nicotinic receptors are associated with the characteristic
      parietal deficit of AD.

PMID- 9040503
TI  - Inhibition of tumor necrosis factor and amelioration of brain infarction in mice.
AB  - Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic brain;
      however, its precise role is not fully understood. We studied the effect of the
      dimeric form of the type I soluble TNF receptor linked to polyethylene glycol
      (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral
      arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or
      intraperitoneally. TNFbp binds and inhibits TNF-alpha. The volume of cortical
      ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24
      h after MCAO. TNFbp produced a significant reduction in the cortical infarct
      volume of vehicle-treated animals (p < 0.001). The reduction in the volume of
      brain damage was 26% in animals that received 3 mg/kg of TNFbp topically. Further
      analysis of TNF-alpha inhibition following acute brain ischemia is indicated.

PMID- 9040504
TI  - Absence of the A1252G mutation in alpha 1-antichymotrypsin in a North American
      population suffering from dementia.
AB  - Associations have been reported between polymorphisms in the gene for alpha 1
      antichymotrypsin (ACT) and both Alzheimer's disease (AD) and cerebrovascular
      disease. An A-to-G substitution at nucleotide position 1,252 of ACT that produces
      a methionine to valine substitution at codon 389 has been found previously in
      four of 32 individuals with cerebrovascular disease from a Japanese population.
      We genotyped 194 individuals [59 controls, 35 with non-AD-type dementia
      (primarily vascular) and 100 with Alzheimer's-type dementia] for this
      polymorphism and found none that carry this polymorphism. Therefore, the allelic
      association of the A1252G mutation of ACT with cerebrovascular disease may be
      confined to the Japanese population and is not generalizable to other
      populations.

PMID- 9040506
TI  - American Association of Dental Schools (AADS) 74th annual session. Orlando,
      Florida, March 15-19, 1997. Abstracts.

PMID- 9040505
TI  - Resting load and modulation of the myofilament Ca2+ sensitivity in rabbit
      cerebral arteries.
AB  - The effect of preload on myofilament Ca2+ sensitivity was examined using alpha
      toxin permeabilization and fura-2 fluorometry in rabbit cerebral arteries. The
      [Ca2+]i-force curves shifted leftward at a high preload, with a decrease in
      median effective concentration of Ca2+ in the permeabilized artery. In the fura-2
      loaded artery, the preload modulated the force without affecting [Ca2+]i levels
      during K+ depolarization, and a high preload moved the [Ca2+]i-force curve upward
      and to the left. It is thus concluded that the preload regulates the Ca2+
      sensitivity of the myofilament and, therefore, may play a role in the regulation
      of cerebral arterial tonus and blood flow.

PMID- 9040507
TI  - Evaluation for cancer in patients with symptomatic DVT.

PMID- 9040508
TI  - Fluoxetine and amitriptyline in the treatment of fibromyalgia.

PMID- 9040509
TI  - Prevention of NSAID-induced GI mucosal injury.

PMID- 9040510
TI  - Parents and pediatric procedures.

PMID- 9040511
TI  - Oral terbutaline after parenteral tocolysis.

PMID- 9040513
TI  - Cardiac troponin T levels in acute MI.

PMID- 9040512
TI  - Treatment of late-state HIV infection.

PMID- 9040514
TI  - Cardiac troponin I levels in unstable angina and non-Q wave AMI.

PMID- 9040515
TI  - The role of folic acid in deficiency states and prevention of disease.
AB  - Folic acid, a water-soluble vitamin, has been used since the 1940s to treat some
      cases of macrocytic anemia without neurologic disease. Folate deficiency is best
      diagnosed with red blood cell folate levels along with macrocytosis and/or
      megaloblastic anemia. In addition to reversing overt deficiency, the vitamin may
      reduce the incidence of neural tube defects by 45% in women who receive 400
      micrograms per day. It is recommended that all women of childbearing age take 400
      micrograms of folate per day. Elevations in homocysteine levels, a metabolite
      intimately associated with folate, are also being found with increasing
      regularity in those with cardiovascular diseases. Homocysteine levels are reduced
      by folic acid administration. Therefore, there is some biologic plausibility, but
      not currently direct proof, for the assumption that folate supplements may
      prevent heart disease, stroke, and peripheral arterial disease. Controlled trials
      should take place before widespread food supplementation with folate is carried
      out on a large scale because of the possibility of outbreaks of permanent B12
      related neurologic damage in those with undiagnosed pernicious anemia. However,
      if a patient has a premature cardiovascular event and has minimal risk factors,
      ordering a test to determine homocysteine level may be advisable, and if
      elevated, treating with folic acid supplement as long as B12 deficiency does not
      coexist.

PMID- 9040516
TI  - A glimpse at physician attitudes about care of patients who suffer from
      depression.

PMID- 9040517
TI  - Alcohol is not a dichotomous variable.

PMID- 9040518
TI  - A two-item screening test for alcohol and other drug problems.
AB  - BACKGROUND: Although nonmedical use of illicit and prescription drugs is not
      uncommon among American adults, the currently recommended screening tests for
      substance use disorders (SUDs) focus only on alcohol. This study reports on the
      criterion validity of a two-item conjoint screening (TICS) test for alcohol and
      other drug abuse or dependence for a primary care sample. METHODS: A random
      sample of 434 primary care patients aged 18 to 59 years responded to nine
      screening items, which emanated from a focus group process. The DSM-III-R
      criteria for SUDs, as operationalized by the Composite International Diagnostic
      Interview-Substance Abuse Module, served as the criterion standard. RESULTS: At
      least one positive response to the TICS ("In the last year, have you ever drank
      or used drugs more than you meant to?" and "Have you felt you wanted or needed to
      cut down on your drinking or drug use in the last year?") discriminated current
      SUDs with approximately 81% sensitivity and specificity. The TICS was
      particularly sensitive to polysubstance use disorders. Respondents with zero
      positive responses had a 7.4% chance of a current SUD; one positive response,
      45.0%; and two positive responses, 75.0%. CONCLUSIONS: More than 80% of young and
      middle-aged patients with current alcohol or other drug problems may be
      recognized by the TICS, which is easily integrated into a clinical interview.

PMID- 9040519
TI  - Knowledge and attitudes about depression among non-generalists and generalists.
AB  - BACKGROUND: The purpose of this study was to learn more about barriers to
      managing depression by comparing knowledge and attitudes about depression among
      physicians, internists, obstetrician-gynecologists, and a reference group of
      psychiatrists. Among the non-psychiatrists, we hypothesized that generalist
      physicians would have more favorable attitudes and greater knowledge about
      depression than non-generalists. METHODS: Survey questionnaires were sent to
      resident and faculty physicians (N = 375) of two university-affiliated medical
      centers. The physicians were classified as non-generalists (medicine
      subspecialists, transitional year interns, and obstetrician-gynecologists),
      generalists (general internists and family physicians), and psychiatrists. A 33
      item written questionnaire assessed knowledge and three attitudinal dimensions:
      attitudes attributed by physicians to patients; physicians' confidence in
      managing depression; and physicians' psychosocial orientation. A knowledge scale
      and an attitudes scale were scored by adding the number of knowledge items
      answered correctly and the more favorable attitudinal responses. Multivariable
      regression was used to identify physician characteristics among non-generalists
      and generalists associated with higher knowledge and attitudinal scores. RESULTS:
      Response rate was 82%. Sixty percent of the respondents were male, 63% were
      resident physicians, and 14% had advanced psychosocial training. Non-generalists
      and generalists had similar demographic characteristics, but psychiatrists were
      significantly more experienced. Psychiatrists had the most favorable attitudes,
      followed by generalists and non-generalists. Compared with non-generalists,
      generalists were more confident in prescribing antidepressants (62% vs 25%), more
      likely to report that treating depression is rewarding (71% vs 39%), and less
      likely to refer to a psychiatrist (58% vs 79%). Generalist classification,
      increased experience, and higher levels of psychosocial training were associated
      with more favorable attitudes. Knowledge scores were significantly higher for
      psychiatrists than for non-generalists and generalists. Among non-psychiatrists,
      correct responses for knowledge items were: treatment efficacy (61%), treatment
      duration (59%), > or = 5 DSM-III-R criteria (52%), and prevalence of depression
      (30%). Among those with incorrect responses, both non-generalists and generalists
      overestimated the prevalence (52%) and underestimated the efficacy of drug
      therapy (30%). CONCLUSIONS: Generalists and non-generalists have similar and
      relatively good basic knowledge about depression. Misperceptions about treatment
      efficacy, and attitudinal barriers, particularly among non-generalists, may
      compromise the physician's ability to diagnose and manage depression.

PMID- 9040520
TI  - Patient-physician trust: an exploratory study.
AB  - BACKGROUND: Patients' trust in their physicians has recently become a focus of
      concern, largely owing to the rise of managed care, yet the subject remains
      largely unstudied. We undertook a qualitative research study of patients' self
      reported experiences with trust in a physician to gain further understanding of
      the components of trust in the context of the patient-physician relationship.
      METHODS: Twenty-nine patients participants, aged 26 to 72, were recruited from
      three diverse practice sites. Four focus groups, each lasting 1.5 to 2 hours,
      were conducted to explore patients' experiences with trust. Focus groups were
      audio-recorded, transcribed, and coded by four readers, using principles of
      grounded theory. RESULTS: The resulting consensus codes were grouped into seven
      categories of physician behavior, two of which related primarily to technical
      competence (thoroughness in evaluation and providing appropriate and effective
      treatment) and five of which were interpersonal (understanding patient's
      individual experience, expressing caring, communicating clearly and completely,
      building partnership/sharing power and honesty/respect for patient). Two
      additional categories were predisposing factors and structural/staffing factors.
      Each major category had multiple subcategories. Specific examples from each major
      category are provided. CONCLUSIONS: These nine categories of physician behavior
      encompassed the trust experiences related by the 29 patients. These categories
      and the specific examples provided by patients provide insights into the process
      of trust formation and suggest ways in which physicians could be more effective
      in building and maintaining trust.

PMID- 9040521
TI  - Primary care and patient perceptions of access to care.
AB  - BACKGROUND: Although much is known about how insurance affects access to care, it
      is unclear whether good primary care contributes to access. The purpose of this
      study was to determine how optimal primary care given by providers at a regular
      place of care, defined in terms of continuity, comprehensiveness, communication,
      and availability, contributed to perceptions of access to care in a large
      population-based probability sample of adults. METHODS: Data were from a cross
      sectional survey of 6674 English- and Spanish-speaking adults 18 to 64 years of
      age, randomly sampled from 41 urban California communities with a range of levels
      of access to care. RESULTS: Following adjustment for sociodemographics and need
      for care, we found that having "optimal" primary care contributed independently
      to improved self-rated access, as did having health insurance, a regular place,
      and a regular provider. The largest difference n access was between having any
      health insurance and not having insurance. Once insurance was available, each
      additional element contributed in a cumulative manner to self-rated access. For
      those with insurance and a regular place, adding optimal primary care improved
      self-rated access to an extent similar to adding a regular provider. CONCLUSIONS:
      We conclude that although providing insurance to the uninsured is the most
      effective means of improving self-rated access, the other elements each improve
      access as well. Once insurance and a regular place are provided, good primary
      care at that place may be equivalent to having a regular provider in terms of
      perceived access. Results support promotion of primary care as a model of health
      care that encourages good access.

PMID- 9040522
TI  - Pain and health status of primary care patients with low back pain.
AB  - BACKGROUND: In addition to the pain caused by low back problems, suffering may
      also adversely affect other aspects of patients' lives. Since there is little
      knowledge about the suffering caused by low back pain, a prospective cohort study
      was undertaken to study pain intensity, perceived health, and daily functioning
      of consecutive patients with low back pain presenting in general practice.
      METHODS: During a period of 2 years, 15 general practitioners enlisted
      consecutive patients with both chronic and recent-onset low back pain in the
      study. From the initial visit, each patient was monitored for a period of 6
      months prospectively. The follow-up consisted of questionnaires mailed every 4
      weeks to determine the intensity of the pain, perceived health, and daily
      functioning. RESULTS: Of the 605 patients identified, 430 were included in the
      follow-up; 6 months after the initial visit, 167 patients were lost to follow-up.
      At baseline, the analyses did not reveal any important differences between acute,
      subacute, and chronic low back pain. Pain intensity, perceived health, and daily
      functioning in all patients tended to resolve over time. This tendency was
      strongest in patients with acute low back pain. The change in pain intensity was
      not strongly correlated with changes in perceived health and daily functioning.
      CONCLUSIONS: All aspects of suffering caused by low back pain tend to diminish
      and resolve over time. No evidence was found of a relationship between perceived
      health or daily functioning and the duration of the low back pain.

PMID- 9040523
TI  - Current trends in tobacco prevention and cessation in Nebraska physicians'
      offices.
AB  - BACKGROUND: Despite years of intervention, few studies describe the extent to
      which recommended tobacco use prevention and cessation activities occur in
      community-based family practices. This study was designed to discover current
      practice patterns in these areas and to describe physician outcome and efficacy
      expectations. METHODS: An exploratory comparative case study of 11 family
      practices used direct observation of practices and clinical encounters, chart
      reviews, and in-depth interviews. Qualitative and quantitative information was
      gathered on (1) intensity of tobacco use prevention and cessation; (2)
      physicians' attitudes and beliefs regarding outcome expectations; and (3)
      physicians' perceptions of their ability to counsel. Qualitative content analysis
      and descriptive statistics were used to construct case studies for comparisons.
      RESULTS: Themes common to most practices included the "provision of little
      prevention" and "a lack of perceived need to address smokeless tobacco."
      Responsibility for tobacco activities fell almost solely to physicians. Although
      physicians felt confident in their counseling skills, the skills they identified
      were fairly basic. Most physicians were pessimistic about the positive effects of
      these activities. None of the practices was using any specifically developed
      "package," and pharmaceutical companies provided almost all patient education
      material. There was considerable variation in intensity of activities because of
      differences in attitudes, expectation, and background. CONCLUSIONS: To increase
      tobacco control activities, practice systems need to be individually evaluated to
      identify what is needed, how it will fit within the practice culture, and how it
      can best be implemented in this specific practice. One-size-fits-all
      interventions probably will not be widely implemented.

PMID- 9040524
TI  - Intranasal desmopressin-associated hyponatremia: a case report and literature
      review.
AB  - We present a case of a 29-year-old woman with a long history of nocturnal
      enuresis who developed symptomatic hyponatremia from water intoxication shortly
      after beginning desmopressin. A MEDLINE search in the English language revealed
      13 prior case reports. All patients presented with seizure, mental status
      changes, or both. Two distinct presentations occurred: one group of patients
      maintained a stable course with desmopressin and developed symptoms related to an
      outside factor. The other group of patients were new to desmopressin and had a
      profound water intoxication response from its use. While the underlying cause was
      from simple overhydration, the quickness of this unanticipated adverse effect is
      noteworthy. The importance of counseling to ensure a family's and a patient's
      understanding of the effects of desmopressin as well as monitoring electrolytes
      periodically may help identify and prevent this serious iatrogenic complication.

PMID- 9040525
TI  - Presentation of recent torture survivors to a family practice center.
AB  - A case series of three patients who recently arrived from Guatemala with
      histories and examinations consistent with torture is reported. A description of
      the clinical presentation of torture survivors is given, with recommendations for
      care by the family physician. The epidemiology and prevention of torture and
      human rights abuses are discussed. Survivors require interventions in the
      following spheres: biological, ie, physical signs of trauma; psychological, eg,
      post-traumatic stress; and social, ie, international prevention of torture by
      governments.

PMID- 9040526
TI  - Family involvement in routine health care.

PMID- 9040528
TI  - Relationships between symptoms of schizophrenia and substance abuse.
AB  - Previous work posits that severity of substance abuse and severity of
      schizophrenic symptoms should be linked by either or both of two mechanisms: self
      regulation of symptoms and drug-induced exacerbation of symptoms. Research on
      these relationships has yielded mixed results. We examined the interrelationships
      of schizophrenic symptoms and substance abuse in 172 patients with co-occurring
      disorders. Relationships were weak or nonexistent, without any consistent
      pattern. Our findings do not support the view that substances are used to self
      regulate symptoms. In addition, our results suggest that substance abuse may lead
      to higher rates of institutionalization through mechanisms other than by
      exacerbating symptoms.

PMID- 9040527
TI  - Neuropsychological function in homeless mentally ill individuals.
AB  - Because little data are available on the neuropsychological functioning of
      severely and persistently mentally ill (SPMI) persons who are homeless, our
      primary goal was to describe accurately and extensively the general
      neuropsychological functioning of a large group of such homeless individuals. In
      addition, we have sought to examine the relationship between some
      neuropsychological functions and demographic, illness, and clinical state
      measures in this population. A 5-hour neuropsychological test battery was
      administered to 116 SPMI homeless individuals. Neuropsychological, diagnostic,
      substance abuse, clinical, and psychopathology data were obtained in a
      standardized manner. SPMI homeless individuals were significantly impaired on a
      wide range of neuropsychological functions. Specific test performances were most
      significantly related to precursor variables (level of education and parental
      socioeconomic status) and state variables (level of psychosis and anticholinergic
      medication dose). Gender and substance abuse had significant effects limited to
      sustained attention. Neuropsychological performance was impaired in this sample
      of homeless SPMI persons. Further research, using profile analysis to directly
      compare groups composed of homeless persons without psychiatric illness or
      demographically matched persons of comparable psychiatric status who are not
      homeless will help clarify the role of homelessness and psychosis on
      neuropsychological function.

PMID- 9040529
TI  - Cognitive impairment and substance abuse history as predictors of the temporal
      stability of negative symptoms in schizophrenia.
AB  - Research has not consistently indicated that negative symptoms in schizophrenia
      are temporally stable. One possible explanation for this is that stable negative
      symptoms are a characteristic of only some individuals with schizophrenia. The
      current study explored whether cognitive impairment and stimulant abuse history
      were associated with amount of change in negative symptom level over a 1-year
      period. Results indicated that among 72 subjects with schizophrenia, performance
      on the Wisconsin Card Sorting Test and history of stimulant abuse significantly
      accounted for 18% of the variance in symptom variability after age, intelligence
      quotient, and initial symptom severity were controlled. As hypothesized, poorer
      performance on the Wisconsin Carding Sorting Test was associated with less
      symptom variability, whereas a more extensive stimulant abuse history was
      associated with greater variability. A discriminant function analysis was able to
      correctly classify 96% of subjects as having stable symptoms but only 30% as
      having unstable symptoms indicating a sensitive, but not specific,
      classification. This finding suggests that cognitive deficits may be a necessary
      but insufficient condition for temporal stability of negative symptoms and that
      negative symptoms in schizophrenia are a complex phenomenon best understood in
      the context of other features of illness and psychosocial variables.

PMID- 9040530
TI  - Does choice of scale for scoring obstetric complications influence their
      relationship to other etiological risk factors in schizophrenia?
AB  - The relationships between obstetric complications (OCs) and both family history
      of psychosis and season of birth were investigated among 70 demographically
      matched pairs of schizophrenic patients and control cases by using OC scores
      produced by three different OC scales. OCs were studied through blindly assessed
      hospital records. The particular OC scale had a great influence on the nature of
      the relationships observed between OCs and both family history and season of
      birth. Across the three scales, the findings varied from no relationship at all
      to completely opposite relationships between OCs and both of the other variables.
      More attention needs to be paid to OC methodological differences as a source of
      variation in study outcome, and attempts should be made to standardize methods
      for OC assessment across studies.

PMID- 9040531
TI  - Adult attention deficit hyperactivity disorder: psychological test profiles in a
      clinical population.
AB  - Compared to attention deficit hyperactivity disorder (ADHD) in children,
      relatively little is known about the clinical characteristics of adults with
      persistent ADHD. We elected to use established tests with age-corrected norms to
      compare the battery of psychological and neuropsychological tests conducted on
      outpatients admitted to our Adult ADHD clinic. ADHD patients scored significantly
      higher than norms on the TPQ novelty seeking and harm avoidance scales and MMPI-2
      scales F, 2, 4, 7, and 8. Further, these patients were impaired on the California
      verbal learning test, the attentional capacity test, and the omissions and
      variability subtests of the test of variables of attention. Adult ADHD had high
      comorbidity with current depressive disorder, antisocial personality disorder,
      and alcohol and drug abuse/dependence. High correlations were found between
      patients' and independent observers' reports of ADHD symptom severity.
      Implications for further research are discussed.

PMID- 9040532
TI  - Predictors of depression among refugees from Vietnam: a longitudinal study of new
      arrivals.
AB  - The present study examined the impact of prearrival traumatic experiences and
      sociodemographic characteristics on future depression among Vietnamese and
      Chinese refugees from Vietnam. This is a longitudinal study of newly arrived
      refugees from Vietnam undergoing a mandatory health screening. A stratified
      consecutive sample of ethnic Chinese and ethnic Vietnamese refugees was drawn.
      The depression subscale of the Indochinese Hopkins symptoms checklist was
      administered to 114 refugees within the first 6 months after arrival in the
      United States and 12 to 18 months later. Ethnic Vietnamese reported more
      prearrival trauma compared with ethnic Chinese. Age was strongly correlated with
      time 2 depression among ethnic Vietnamese but not among ethnic Chinese.
      Multivariate linear regression analysis revealed that being a veteran, older,
      unattached, less proficient in English, ethnic Vietnamese, and more depressed at
      baseline predicted higher depression at follow-up. Although prearrival trauma
      predicted future depression, other sociodemographic characteristics assumed more
      importance with time.

PMID- 9040533
TI  - Normalizing acute care: a day hospital/crisis residence alternative to inpatient
      hospitalization.
AB  - Normalization is the use of culturally valued means to enable people with
      disabilities to live culturally valued lives. In this article, the authors
      describe an effort to bring normalization practices to acute psychiatric care.
      They describe a day hospital/crisis respite diversion program that serves as an
      alternative to acute inpatient hospitalization and sketch the research project
      that fostered it. The authors argue that a day hospital/ crisis respite provides
      effective clinical care comparable to inpatient hospitalization but achieves
      greater potential for recovery through a normalizing philosophy and practice. An
      implication of this finding is that such programs based on the principle of
      normalization may be both cost effective as well as more empowering for patients.

PMID- 9040534
TI  - Language planning processing in schizophrenia using the active or passive voice.

PMID- 9040535
TI  - Effect of noise stress on chronic fatigue syndrome patients.

PMID- 9040536
TI  - Dissociative experiences scale and MMPI-2 scores in video poker gamblers, other
      gamblers, and alcoholic controls.

PMID- 9040537
TI  - Retinoic acid increases cellular retinol binding protein II mRNA and retinol
      uptake in the human intestinal Caco-2 cell line.
AB  - Cellular retinol binding protein II (CRBPII) is an abundant small intestinal
      protein that facilitates vitamin A trafficking and metabolism. The magnitude of
      retinol uptake and metabolism correlate to CRBPII levels in the human intestinal
      Caco-2 cell line. To investigate the importance of retinoic acid receptor
      response elements in the promoter of the CRBPII gene, retinoic acid regulation of
      CRBPII expression and vitamin A absorption was studied in differentiated Caco-2
      cells. All-trans- or 9-cis-retinoic acid increased CRBPII mRNA levels two- to
      threefold. This was associated with a 50% increase in retinol absorption.
      Retinoic acid receptor beta and apolipoprotein A1 regulatory protein-1, two
      nuclear receptors that bind to the CRBPII promoter, were also induced, whereas
      other retinoid and orphan receptors were not. Thus, retinoic acid may regulate
      CRBPII expression directly or by selectively changing levels of nuclear receptors
      or other factors. These studies are the first to demonstrate that retinoic acid
      can modulate endogenous CRBPII mRNA levels and retinol absorption in Caco-2 cells
      and suggest that human intestinal vitamin A absorption may be regulated by
      retinoids.

PMID- 9040538
TI  - Butyrate alters activity of specific cAMP-receptor proteins in a transgenic mouse
      colonic cell line.
AB  - There is great interest in utilizing butyrate as a chemotherapeutic agent. To
      elucidate its mechanism of action, the effect of butyrate on cAMP receptor
      protein kinase (PKA) activity in young adult mouse colon (YAMC) cells isolated
      from transgenic mice bearing a temperature sensitive mutation of the SV40 large T
      antigen gene was investigated. Conditionally immortalized cultures were plated at
      the permissive temperature (33 degrees C) or growth arrested by incubation at the
      nonpermissive temperature (39 degrees C). In addition, cells were incubated at 33
      degrees C with or without 1 mmol/L butyrate for 24 h. Butyrate treatment reduced
      cell proliferation by 28% and enhanced apoptosis by 350% compared with cultures
      not exposed to butyrate. The PKA type I/II isozyme activity ratio was lower (P <
      0.05) in cells incubated with butyrate. The relative level of PKA I isozyme was
      higher in proliferating cells at 33 degrees C (63% of total PKA), while the
      relative level of PKA II was higher in nonproliferating cells undergoing
      apoptosis at 39 degrees C (59% of total PKA). Neither incubation conditions (33
      vs. 39 degrees C) nor butyrate treatment altered total PKA activity. When YAMC
      cells were incubated with 8-CI-cAMP, an activator of PKA II, growth was markedly
      inhibited in cells at both temperatures. Consistent with in vitro data, increased
      PKA I isozyme levels were associated with dysregulated growth in vivo.
      Specifically, the relative level of PKA I isozyme was three- to fivefold higher
      in rat colonic tumors compared with normal nontransformed colonic mucosa. These
      data indicate that the biological effects of butyrate on colonocyte proliferation
      and apoptosis are associated with changes in PKA isozyme-dependent signal
      transduction, and the YAMC cell line is a relevant model to examine the molecular
      mechanisms by which dietary-derived factors affect relative cancer risk.

PMID- 9040539
TI  - Zinc deficiency in adult rats reduces the relative abundance of testis-specific
      angiotensin-converting enzyme mRNA.
AB  - Zinc deficiency results in reduced testicular angiotensin-converting enzyme (ACE)
      activity and reduced amounts of ACE protein in the testes of young rats. In the
      present study, we examined the effect of zinc deficiency on the relative
      abundance of testicular ACE mRNA and its relationship to ACE activity over time.
      Forty-five male rats at 7 wk of age were placed on one of three feeding regimens:
      1) a diet adequate in zinc, 2) a diet deficient in zinc and 3) a diet adequate in
      zinc that was fed in an amount equal to that consumed by a paired mate fed the
      zinc-deficient diet. Rats were killed after 3, 5 and 7 wk. Rats fed the zinc
      deficient diet had significantly lower (P < 0.01) body weight gain and testis
      weight at each week sampled than the other groups. They also showed compromised
      zinc status as evidenced by significantly lower (P < 0.01) serum and testis zinc
      concentrations. At each period, rats fed the zinc-deficient diet had
      significantly lower (P < 0.01) testicular ACE activity than rats fed either of
      the zinc-adequate diets. Coinciding with low ACE activity, there was a lower (P <
      0.01) relative abundance of ACE mRNA in the group for the zinc-deficient diet
      than in either of the zinc-adequate groups. The results suggest that much of the
      low ACE activity in the testis of rats in the latter stages of zinc deficiency is
      attributable to a reduction in ACE gene transcription. However, an effect of the
      deficiency on ACE mRNA turnover is not ruled out.

PMID- 9040540
TI  - Male rats fed methyl- and folate-deficient diets with or without niacin develop
      hepatic carcinomas associated with decreased tissue NAD concentrations and
      altered poly(ADP-ribose) polymerase activity.
AB  - Folate is an essential cofactor in the generation of endogenous methionine, and
      there is evidence that folate deficiency exacerbates the effects of a diet low in
      choline and methionine, including alterations in poly(ADP-ribose) polymerase
      (PARP) activity, an enzyme associated with DNA replication and repair. Because
      PARP requires NAD as its substrate, we postulated that a deficiency of both
      folate and niacin would enhance the development of liver cancer in rats fed a
      diet deficient in methionine and choline. In two experiments, rats were fed
      choline- and folate-deficient, low methionine diets containing either 12 or 8%
      casein (12% MCFD, 8% MCFD) or 6% casein and 6% gelatin with niacin (MCFD) or
      without niacin (MCFND) and were compared with folate-supplemented controls. Liver
      NAD concentrations were lower in all methyl-deficient rats after 2-17 mo. At 17
      mo, NAD concentrations in other tissues of rats fed these diets were also lower
      than in controls. Compared with control values, liver PARP activity was enhanced
      in rats fed the 12% MCFD diet but was lower in MCFND-fed rats following a further
      reduction in liver NAD concentration. These changes in PARP activity associated
      with lower NAD concentrations may slow DNA repair and enhance DNA damage. Only
      rats fed the MCFD and MCFND diets developed hepatocarcinomas after 12-17 mo. In
      Experiment 2, hepatocarcinomas were found in 100% of rats fed the MCFD and MCFND
      diets. These preliminary results indicate that folic acid deficiency enhances
      tumor development. Because tumors developed in 100% of the MCFD-fed rats and
      because tissue concentrations of NAD in these animals were also low, further
      studies are needed to clearly define the role of niacin in methyl-deficient rats.

PMID- 9040541
TI  - Dietary (n-3) polyunsaturated fatty acids suppress murine lymphoproliferation,
      interleukin-2 secretion, and the formation of diacylglycerol and ceramide.
AB  - Elucidation of the mechanism(s) by which dietary fish oil, enriched in
      eicosapentaenoic acid (EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)],
      suppresses the inflammatory process is essential in maximizing this potentially
      therapeutic effect. Murine T-lymphocyte function and signal transduction were
      examined in response to a low fat, short term diet enriched in highly purified
      EPA or DHA ethyl esters. For 10 d, mice were fed comparable diets containing
      either 3% safflower oil ethyl esters (SAF), 2% SAF + 1% arachidonic acid
      triglyceride (AA), 2% SAF + 1% EPA, or 2% SAF + 1% DHA. Concanavalin A-induced T
      lymphocyte proliferation in splenocyte cultures was significantly suppressed by
      dietary EPA and DHA while AA had no effect relative to the SAF control. The
      suppressed proliferative response in EPA- and DHA-fed mice was preceded
      temporally by a significant reduction in IL-2 secretion. Kinetics of mitogen
      induced diacyl-sn-glycerol (DAG) and ceramide production did not differ
      significantly between SAF and AA diet groups. In contrast, DAG production was
      significantly suppressed in EP- and DHA-fed mice relative to the SAF and AA
      groups. The reduced DAG mass was paralleled by reduced ceramide mass following
      EPA and DHA feeding compared to the SAF and AA groups. Thus, low dose, short term
      dietary exposure to highly purified EPA or DHA appears to suppress mitogen
      induced T-lymphocyte proliferation by inhibiting IL-2 secretion, and these events
      are accompanied by reductions in the production of essential lipid second
      messengers, DAG and ceramide.

PMID- 9040542
TI  - Splenocyte glutathione and CD3-mediated cell proliferation are reduced in mice
      fed a protein-deficient diet.
AB  - Protein-energy malnutrition (PEM) is associated with decreased host immune
      defense. Glutathione (GSH) status is reported to be decreased in PEM, and GSH is
      important for lymphocyte function. The objective of the present study was to
      investigate the effects of PEM and dietary repletion (RP) on GSH status in
      various tissues and splenocytes and on CD3-mediated calcium mobilization and cell
      proliferation of splenic T-lymphocytes. For the PEM model, mice were fed a 0.5%
      protein diet (LP group) for 4 or 6 wk, and control mice were fed a 15% protein
      diet (CP group). In the RP study, LP mice were fed the 15% protein diet for 3 d,
      1 wk, 2 wk or 3 wk (RP groups). Glutathione concentrations were significantly
      lower in liver, lung, heart and spleen of LP mice compared with CP mice at 4 and
      6 wk. Splenocytes from LP mice were significantly lower in number and had a lower
      intracellular GSH concentration, depressed CD3-stimulated T-lymphocyte
      proliferation in culture media without thiol supplementation (2-mercaptoethanol),
      and enhanced CD3-stimulated proliferation in thiol-supplemented culture media
      compared with splenocytes from CP mice. CD3-stimulated calcium mobilization was
      significantly lower in CD8+, but not CD4+, splenocytes from LP mice. Within 1 wk
      of dietary repletion, splenocyte GSH concentration was normal and splenocyte
      numbers were greater, and in vitro sensitivity of CD3-stimulated T-lymphocyte
      proliferation to thiol was lower, compared with LP mice. Glutathione status in
      vivo and thiol supplementation in vitro seem to modulate the signal transduction
      pathway for T-lymphocyte proliferation in mice with PEM.

PMID- 9040543
TI  - Early feeding of an energy dense diet during acute shigellosis enhances growth in
      malnourished children.
AB  - In a controlled clinical trial, we examined the effect of the short-term feeding
      of an energy-dense milk cereal formula in malnourished children with clinically
      severe dysentery due to acute shigellosis. Seventy-five malnourished children,
      aged 12-48 mo, passing blood or blood with mucous in the stool for < or = 96 h,
      were offered a hospital diet. In addition, study children (n = 36) were offered a
      milk-cereal formula with an energy of 5 kJ/g (an 11% protein diet); similarly,
      control children (n = 39) were offered a milk-cereal formula with an energy
      content of 2.5 kJ/g (an 11% protein diet). Patients were admitted to the
      metabolic ward of the Clinical Research and Service Centre, Dhaka, at the
      International Centre for Diarrhoeal Disease Research, Bangladesh. Patients were
      studied for 10 hospital days and were then followed up at home after 30 d. After
      10 d of dietary intervention, children in the study group had a significantly
      greater increase vs. controls in weight-for-age (6 vs. 3%, P < 0.001) and in
      weight-for-height (7 vs. 3%, P < 0.001). Serum prealbumin concentrations were
      significantly higher (study vs. control) after 5 d (0.214 vs. 0.170 g/L, P =
      0.01) and after 10 d (0.244 vs. 0.193 g/L, P = 0.006) of the study. Greater
      weight-for-age was sustained at home 1 mo after discharge (8 vs. 5%, P = 0.005)
      from the hospital. Similarly, higher weight-for-height was sustained 1 mo after
      discharge (8 vs. 5%, P = 0.01). During their stay at home, there was no dietary
      intervention. The results of this study suggest that short-term feeding of an
      energy-dense diet enhances growth in malnourished children with acute dysentery
      due to shigellosis.

PMID- 9040544
TI  - Use of thyroid stimulating hormone testing in newborns to identify iodine
      deficiency.
AB  - Iodine deficiency has traditionally been associated with goiter and cretinism.
      More recently, iodine deficiency has been recognized as the leading worldwide
      cause of preventable intellectual impairment. Intellectual and neurologic
      deficits occur because of a lack of thyroid hormone during critical phases of
      brain development. More sensitive biologic tests may be useful in determining the
      true extent of iodine deficiency in populations. Thyroid stimulating hormone
      (TSH) levels among urban newborns from countries with known iodine deficiency
      problems were determined using a sensitive whole-blood spot assay. Results found
      prevalences of high TSH (> 5 mU/L whole blood units using a sensitive monoclonal
      assay) ranging from 32-80% compared with a prevalence of 3% usually found in
      iodine-replete areas. These findings suggest that developing brains of newborns
      are at risk from the detrimental effects of iodine deficiency in these urban
      areas. The results presented suggest the need for effective intervention programs
      in urban areas as well.

PMID- 9040545
TI  - Breast-feeding status alters the effect of vitamin A treatment during acute
      diarrhea in children.
AB  - Vitamin A administration in children reduces the incidence of severe diarrhea
      during the subsequent few months. We therefore examined the effect of treatment
      with vitamin A during acute diarrhea on the episode duration and severity. In a
      double-blind controlled field trial, 900 children 1 to 5 y of age with acute
      diarrhea of < or = 7 d duration were randomly assigned to receive vitamin A (60
      mg) or a placebo. Children were followed up at home every alternate day until
      they recovered from the diarrheal episode. In all study children, those treated
      with vitamin A had a significantly lower risk of persistent diarrhea [odds ratio
      (OR) 0.30, 95% confidence interval (CI) 0.07-0.97], but there was no effect on
      the mean diarrheal duration or the mean stool frequency, in the subgroup of
      children who were not breast-fed, the mean diarrheal duration [ratio of geometric
      means (GM) 0.84, 95% CI 0.72-0.97], mean number of stools passed after the
      intervention (ratio of GM 0.73, 95% CI 0.56-0.95), the proportion of episodes
      lasting > or = 14 d (P = 0.002) and the percentage of children who passed watery
      stools on any study day (OR 0.40, 95% CI 0.21-0.77) were significantly lower in
      those treated with vitamin A. We conclude that administration of vitamin A during
      acute diarrhea may reduce the severity of the episode and the risk of persistent
      diarrhea in non-breast-fed children. Similar benefit was not seen in breast-fed
      children.

PMID- 9040546
TI  - Consumption of a high fat diet impairs reproductive performance in Sprague-Dawley
      rats.
AB  - Rats made obese by cafeteria feeding have poor reproductive outcomes. To
      investigate this phenomenon in animals fed a more nutritionally adequate diet,
      female rats were fed either a high fat (HF) (modified AIN-76A, 35 g fat/100 g
      diet) or a control (C) (AIN-76A, 5 g fat/100 g diet), diet, beginning at 27 d of
      age. To assess reproductive performance, rats were studied at d 0, 5 and 18 of
      pregnancy and on d 3 of lactation. Pregnancy rates were significantly (P < 0.001)
      lower in the high fat-fed rats than in the control-fed rats (56.4 and 89.1%,
      respectively). There was no difference between groups in total pregnancy weight
      gain or the proportion of weight gained during pregnancy that was retained by the
      dam. High fat-fed dams tended to gain weight more rapidly early in gestation than
      control-fed dams and then less rapidly than control-fed dams during the last week
      of gestation. Litter number and pup weight at birth did not differ between
      groups, but of high fat-fed pups had significantly higher (P < 0.04) mortality
      rates than pups of control-fed dams (16.5 and 7.7%, respectively) over the first
      3 d of life. Control-fed dams experienced the expected reduction (P < 0.05) in
      plasma insulin concentrations between the end of pregnancy and early lactation,
      but high fat-fed dams did not. Thus, physiological mechanisms controlling
      distribution of metabolic fuels may not be functioning properly in high fat-fed
      dams. Therefore, consuming a high fat diet reduces a rat's capacity to conceive
      and ability to maintain her litter during the perinatal period.

PMID- 9040547
TI  - Parenteral zinc supplementation in adult humans during the acute phase response
      increases the febrile response.
AB  - The acute phase response (APR) that follows injury or infection is characterized
      by a decrease in serum zinc concentrations, which we hypothesized benefits the
      host. Additionally, we proposed that preventing this decline by supplementing
      zinc would result in an exaggerated APR as indicated by elevated temperatures,
      increased serum cytokine concentrations, interleukin 6 and the acute phase
      protein (ceruloplasmin). A prospective, randomized, double-blinded, clinical
      trial was conducted. Patients on home parenteral nutrition with a diagnosis of
      catheter sepsis and patients with a diagnosis of pancreatitis, also on total
      parenteral nutrition (TPN), were recruited for the study. Following enrollment,
      block randomization was used to assign patients to receive 0 mg (n = 23) or 30 mg
      (n = 21) of zinc per day for the first 3 d of TPN. Blood samples for measurement
      of serum zinc, copper, ceruloplasmin and interleukin-6 were obtained upon
      enrollment and on d 1 through 3 of TPN. The highest temperatures reported on
      these days in the medical record were also recorded. Repeated measures ANOVA was
      used to determine differences in the primary outcome variables over time. No
      significant differences between groups were observed in serum interleukin-6 or
      ceruloplasmin concentrations. A significantly higher (P = 0.035) temperature was
      observed in the zinc-supplemented group compared with the control group on d 3 of
      parenteral nutrition. We conclude that parenteral zinc supplementation in
      patients experiencing a mild APR resulted in an exaggerated APR as evidenced by a
      significantly higher febrile response.

PMID- 9040548
TI  - Weight loss is greater with consumption of large morning meals and fat-free mass
      is preserved with large evening meals in women on a controlled weight reduction
      regimen.
AB  - The purpose of this study was to determine whether meal ingestion pattern [large
      morning meals (AM) vs. large evening meals (PM)] affects changes in body weight,
      body composition or energy utilization during weight loss. Ten women completed a
      metabolic ward study of 3-wk weight stabilization followed by 12 wk of weight
      loss with a moderately energy restricted diet [mean energy intake +/- SD = 107 +/
      6 kJ/(kg.d)] and regular exercise. The weight loss phase was divided into two 6
      wk periods. During period 1, 70% of daily energy intake was taken as two meals in
      the AM (n = 4) or in the PM (n = 6). Subjects crossed over to the alternate meal
      time in period 2. Both weight loss and fat-free mass loss were greater with the
      AM than the PM meal pattern: 3.90 +/- 0.19 vs. 3.27 +/- 0.26 kg/6 wk, P < 0.05,
      and 1.28 +/- 0.14 vs. 0.25 +/- 0.16 kg/6 wk, P < 0.001, respectively. Change in
      fat mass and loss of body energy were affected by order of meal pattern
      ingestion. The PM pattern resulted in greater loss of fat mass in period 1 (P <
      0.01) but not in period 2. Likewise, resting mid-afternoon fat oxidation rate was
      higher with the PM pattern in period 1 (P < 0.05) but not in period 2,
      corresponding with the fat mass changes. To conclude, ingestion of larger AM
      meals resulted in slightly greater weight loss, but ingestion of larger PM meals
      resulted in better maintenance of fat-free mass. Thus, incorporation of larger PM
      meals in a weight loss regimen may be important in minimizing the loss of fat
      free mass.

PMID- 9040549
TI  - Erythrocyte incorporation of iron is similar in infants fed formulas fortified
      with 12 mg/L or 8 mg/L of iron.
AB  - Although feeding of formulas with iron concentration of 215 mumol/L (12 mg/L) is
      a reliable means of preventing iron deficiency, high intakes of iron may
      adversely affect absorption of copper and zinc. Because data are not available to
      establish whether fortification at a lower level would result in equivalent iron
      absorption, we tested the hypothesis that iron absorption is greater by infants
      fed formulas with an iron concentration of 215 mumol/L (12 mg/L) than by those
      fed formulas with an iron concentration of 143 mumol/L (8 mg/L). Fifty-two normal
      infants entered the study at 112 +/- 4 d of age, and 46 of these were
      successfully studied until 196 d of age. Using the stable isotope 58Fe, we
      determined erythrocyte incorporation of iron by infants fed Formula 8 [iron
      approximately 143 mumol/L (8 mg/L)] and by infants fed Similac with Iron [iron
      approximately 215 mumol/L (12 mg/L)]. On each of three test days beginning at 154
      d of age, a major portion of the formula was labeled with 58Fe. Geometric mean
      erythrocyte incorporation of iron adjusted for plasma ferritin concentration at
      168 d of age was 4.82 mumol/d (0.269 mg/d) by infants fed Formula 8 and 5.21
      mumol/d (0.291 mg/d) by infants fed Similac with Iron. Corresponding values at
      196 d of age were 5.12 and 5.41 mumol/d (0.286 and 0.302 mg/d). The differences
      in quantity of iron incorporated into erythrocytes by infants fed Formula 8 and
      Similac with Iron were not statistically significant (P = 0.66 at 168 d of age, P
      = 0.75 at 196 d of age) and were judged to be nutritionally trivial. Because we
      were unable to provide support for our hypothesis that iron absorption is greater
      by infants fed formulas providing 215 mumol (12 mg) of iron per liter than by
      those fed formulas providing 143 mumol (8 mg) of iron per liter, we conclude
      that, pending the results of further studies, It is reasonable to decrease the
      iron concentration of iron-fortified infant formulas.

PMID- 9040550
TI  - Differentiation of ingested and endogenous bifidobacteria by DNA fingerprinting
      demonstrates the survival of an unmodified strain in the gastrointestinal tract
      of humans.
AB  - Consumption of bifidobacteria as a dietary adjunct has received considerable
      attention for its possible role in the maintenance of gastrointestinal health.
      However, speculation exists about these presumed health benefits because of an
      inability to assess the fate and mechanism of action of ingested bifidobacteria.
      Thus, our objective was to examine the fate of ingested bifidobacteria through
      the gastrointestinal tract. Variations in the highly conserved 16S ribosomal DNA
      (rDNA) of bifidobacteria from six male subjects (18 to 35 y old) were assessed by
      restriction fragment length polymorphism (RFLP) analysis. During the 16-d study,
      10(10) colony-forming units (CFU) of a commercially available bifidobacteria were
      delivered to subjects in fluid milk for each of 8 d. During the remaining 8 d,
      subjects consumed milk without bifidobacteria. Feces were collected at 4-d
      intervals and plated on selective media. For each subject, 10-15 colonies were
      randomly selected and used as template for PCR-amplification of 16S rDNA. 16S
      rDNA was restriction digested and resolved by electrophoresis. The 16S rDNA-RFLP
      of the ingested bifidobacteria was unique compared with bifidobacteria found in
      subjects prior to the feeding study. When subjects consumed bifidobacteria, a 16S
      rDNA-RFLP identical to that of the ingested bifidobacteria was observed in feces.
      The concentration of the ingested bifidobacteria in feces increased to 67.2 +/-
      8.5% (mean +/- SEM) of total bifidobacteria. After feeding stopped, the ingested
      bifidobacteria diminished and became undetectable. Using this molecular approach
      to monitor ingested bifidobacteria, we demonstrate the kinetics of passage of
      this organism through the gastrointestinal tract of healthy humans.

PMID- 9040551
TI  - A compartmental model depicting short-term kinetic changes in selenium metabolism
      in ewes fed hay containing normal or inadequate levels of selenium.
AB  - Changes in Se metabolism were studied in ewes fed hay containing normal or
      inadequate levels of Se. After intravenous injection of 75Se-sodium selenite,
      blood, feces and urine were collected at different times, and the concentrations
      of labeled and unlabeled Se were determined. Ewes were killed 1, 5, 9 or 14 d
      after tracer injection, and tissues were obtained for determination of
      radioactivity and Se concentration. The data were fitted to a compartmental model
      using the SAAM/CONSAM computer program, and kinetic parameters and steady-state
      transport rates were estimated. Daily Se intake (Vi) and fecal excretion (VF)
      were significantly (P < 0.001) higher in the ewes fed normal hay (6.06 +/- 1.09
      and 3.36 +/- 0.88 mumol/d, respectively) than in those fed Se-deficient hay (0.64
      +/- 0.18 and 0.26 +/- 0.15 mumol/d). The net absorption (Va) of Se was
      significantly higher in ewes fed normal hay [3.19 +/- 0.82 mumol/d by the balance
      method, Va = Vi-(VF -Vf) (Vf = endogenous fecal Se) and 1.05 +/- 0.38 mumol/d by
      using the model (plasma entry rate, U(1))] than in those fed hay deficient in Se
      [0.57 +/- 0.33 mumol/d (balance) and 0.28 +/- 0.08 mumol/d (model)]. The
      efficiency of absorption [alpha = U(1) divided by Vi] was significantly higher
      (0.46 +/- 0.19) in ewes fed Se-deficient hay than in those fed normal hay (0.18
      +/- 0.09). Simultaneous fitting of the tracer data of both the groups showed that
      changes in hepatic extraction and urinary and fecal excretion were sufficient and
      necessary to account for the kinetic differences observed between treatments.

PMID- 9040552
TI  - Vitamin E improves the free radical defense system potential and insulin
      sensitivity of rats fed high fructose diets.
AB  - The purpose of this study was to investigate the effects of vitamin E in rats fed
      a high fructose diet which leads to insulin resistance, on some components of the
      free radical defense system and on insulin sensitivity. The rats (postweaning, 50
      g) were divided into three groups: the control group (C, n = 16), which received
      a purified diet containing 60 g/100 g carbohydrates, the high fructose-fed group
      (FT, n = 16),fed a diet in which 56.8% of the carbohydrate as fructose, and a
      high fructose and vitamin E-fed group (FVE, n = 16), fed the FT diet supplemented
      with 3.4 g vitamin E/kg diet (vs. 0.17 g/kg in C and FT groups). The duration of
      the treatment was 6 wk. Insulin sensitivity was determined in half of the rats in
      each group using the euglycemic hyperinsulinic glucose clamp technique. The
      remaining rats were investigated for plasma glucose, insulin, triglyceride and
      fructosamine concentrations and for components of the free radical defense
      system. The FT group had a significantly lower insulin sensitivity than the C
      group. Basal glycemia was not different among the groups. In comparison with the
      C group, the FT group had a greater lipid peroxidation, as indicated by the
      higher concentrations of plasma thiobarbituric acid reactive substances (TBARS)
      and blood disulfide glutathione (GSSG) and the lower Cu-Zn superoxide dismutase
      (Cu-Zn SOD) activity. These markers approached the values of the controls after
      addition of vitamin E. Moreover, the FVE group had a higher insulin sensitivity
      than the FT group, but it remained lower than in the C group. These results show
      that a high fructose diet in rats leads to insulin resistance and a defect in the
      free radical defense system. Vitamin E supplementation improves insulin
      sensitivity in fructose-fed rats.

PMID- 9040553
TI  - Energy values of non-starch polysaccharides: comparative studies in humans and
      rats.
AB  - Energy values of non-starch polysaccharides (NSP) were estimated from NSP
      fermentability and from digestible energy balances in human subjects and in rats.
      During four studies, humans consumed four low fiber control diets and six high
      fiber diets. For the rat diets, duplicates of the foods consumed by humans were
      mixed together, freeze-dried and ground. Calculated from fermentability, partial
      digestible energy values of NSP in humans and rats, respectively, were 8.2 +/-
      1.3 and 5.7 +/- 1.2 (P = 0.0013, fruits and vegetables), 11.4 +/- 0.7 and 5.7 +/-
      3.2 (P = 0.0001, citrus fiber), 5.0 +/- 2.1 and 2.2 +/- 3.3 (P = 0.0429, barley
      fiber at high protein intake), 4.4 +/- 1.8 and 2.4 +/- 2.0 (P = 0.0561, barley
      fiber at low protein intake), 6.7 +/- 1.4 and 7.6 +/- 1.2 (P = 0.296, coarse
      whole meal rye bread), and 7.1 +/- 0.6 and 6.1 +/- 1.7 (P = 0.157, fine whole
      meal rye bread) kJ/g NSP. Calculated from energy balances, partial digestible
      energy values of NSP in humans and rats, respectively, were 2.1 +/- 3.5 and -5.0
      +/- 4.0 (P = 0.026, fruits and vegetables), 10.7 +/- 5.1 and 1.4 +/- 5.6 (P =
      0.003, citrus fiber), 1.6 +/- 5.1 and -17.8 +/- 8.6 (P = 0.0001, barley fiber at
      high protein intake), -2.6 +/- 4.9 and -9.3 +/- 8.2 (P = 0.044, barley fiber at
      low protein intake), -3.0 +/- 7.0 and 0.9 +/- 2.5 (P = 0.27, coarse whole meal
      rye bread), and 0.9 +/- 5.1 and 0.6 +/- 3.7 (P = 0.89, fine whole meal rye bread)
      kJ/g NSP. Net energy values were 70% of digestible energy values. Differences
      between species were significant for NSP in fruits and vegetables, citrus fiber,
      and barley fiber at high protein intake. Most energy values calculated from
      energy balances were significantly lower than values calculated from NSP
      fermentation, with differences being greater in rats than in humans. Thus, the
      energy values of some types of NSP contained in mixed diets could not be
      estimated accurately from NSP fermentability either in humans or rats. In
      addition, our results suggest that the rat is not always a suitable model of
      humans for predicting energy values of NSP in mixed diets.

PMID- 9040554
TI  - Vitamin B-6 normalizes the altered sulfur amino acid status of rats fed diets
      containing pharmacological levels of niacin without reducing niacin's
      hypolipidemic effects.
AB  - Niacin (nicotinic acid) in large doses (> 2 g) has been increasingly the choice
      of lipid-lowering agent by clinicians. However, the potential risks of the use of
      high doses of the vitamin have not been critically considered in the same way as
      has the use of other lipid-lowering drugs. The present study provides evidence
      that pharmacological levels of niacin interfere with the metabolism of
      methionine, leading to hyperhomocysteinemia and hypocysteinemia. Male Sprague
      Dawley rats were fed a semisynthetic diet supplemented with either 400 or 4000 mg
      niacin/kg (compared with 47 mg/kg diet in the control diet). In Experiment 1,
      feeding these diets for 3 wk resulted in a dose-related increase in the plasma
      and urine methionine concentrations while cysteine levels were decreased. This
      altered methionine metabolism was accompanied by a lower plasma vitamin B-6
      concentration in niacin-supplemented rats compared with controls. In Experiment
      2, the methionine and cysteine levels in plasma and urine were normalized when
      vitamin B-6 (10 mg/kg diet) was added to the diet containing 4000 mg niacin/kg
      and fed for 6 wk. This experiment also showed that plasma and urine homocysteine
      concentrations were increased by niacin and normalized by vitamin B-6. The
      hypolipidemic action of niacin was unaffected by the presence of vitamin B-6.
      These results indicate that niacin at large dosages interferes with methionine
      metabolism by affecting vitamin B-6 status. The treatment of dyslipidemia with
      simultaneous administration of niacin and vitamin B-6 could be a better therapy
      than the use of niacin alone.

PMID- 9040555
TI  - Dietary manipulation of plasma carotenoid concentrations of squirrel monkeys
      (Saimiri sciureus).
AB  - Primate retinas accumulate the dihydroxy xanthophylls, lutein and zeaxanthin,
      from the diet via the plasma. Control of plasma concentrations of these
      carotenoids may be useful for prevention of retinal disease by manipulating
      carotenoid content of the retina. We have measured the plasma response of male
      squirrel monkeys to changes in the carotenoid content of a nonpurified diet. We
      have also supplemented the diet with zeaxanthin and beta-carotene. Plasma
      responses to dietary changes were rapid. Within one week, most of the change in
      plasma concentrations had already occurred. Within two weeks of increasing
      zeaxanthin intake, plasma zeaxanthin concentrations were at a new, relatively
      stable level. beta-carotene concentrations in the plasma were low while the
      monkeys were consuming a standard laboratory diet, and were only slightly
      increased by supplementation. Plasma lutein concentrations were unaffected by
      zeaxanthin supplementation. Our results suggest that it should be possible to
      manipulate plasma concentrations of each of the retinal carotenoids with little
      impact on the plasma concentrations of the other. This will facilitate
      exploration of the rates of accumulation of lutein and zeaxanthin in the retina,
      as well as exploration of the possibility of bioconversion from one xanthophyll
      to another.

PMID- 9040556
TI  - Selected indigestible oligosaccharides affect large bowel mass, cecal and fecal
      short-chain fatty acids, pH and microflora in rats.
AB  - Certain indigestible oligosaccharides may benefit gastrointestinal tract health
      via fermentation and proliferation of desirable bacterial species. The purpose of
      this study was to elucidate effects of selected oligosaccharides on cecal and
      fecal short-chain fatty acid (SCFA) concentration, pH, total large bowel wet
      weight and wall weight, and gut microbiota levels in rats. Fifty male Sprague
      Dawley rats were randomly assigned to one of five treatments: 1) control diet; 2)
      control diet + 5% microcrystalline cellulose (5% CC); 3) control diet + 5% CC +
      6% fructooligosaccharides; 4) control diet + 5% CC + 6% oligofructose; or 5)
      control diet + 5% CC + 6% xylooligosaccharides. The control diet consisted of
      (dry matter basis) 20% protein, 65% carbohydrate, 10.5% fat, vitamin and mineral
      mixes. The duration of the study was 14 d. The oligofructose- and
      fructooligosaccharide-containing diets resulted in higher cecal butyrate
      concentrations compared with the control, cellulose and xylooligosaccharide
      diets. Generally, total cecal SCFA pools were higher while pH was lower from
      ingesting oligosaccharide-containing diets compared with control or cellulose
      diets. Cecal total weight and wall weight were higher from oligosaccharide
      consumption, whereas colonic total wet weight was higher for rats consuming
      xylooligosaccharides compared with other treatments; colon wall weight was
      unaffected by treatments. Cecal bifidobacteria and total anaerobes were higher
      whereas total aerobes were lower in rats fed oligosaccharide diets compared with
      those fed the control diet. Cecal lactobacilli levels were unaffected by
      treatment. Dietary incorporation of fermentable, indigestible oligosaccharides,
      by providing SCFA, lowering pH, and increasing bifidobacteria, may be beneficial
      in improving gastrointestinal health.

PMID- 9040557
TI  - An enteral formula containing fish oil, indigestible oligosaccharides, gum arabic
      and antioxidants affects plasma and colonic phospholipid fatty acid and
      prostaglandin profiles in pigs.
AB  - Evidence supports a pathogenic role of arachidonic acid-derived inflammatory
      mediators within the gastrointestinal tract of patients with inflammatory bowel
      disease. The purpose of this study was to assess the effects of an ulcerative
      colitis nutritional formula (UCNF) containing oligosaccharides, fish oil, gum
      arabic and antioxidants on plasma and colonic phospholipid fatty acid and
      prostaglandin profiles in pigs. Twenty-four growing barrows in two replications
      were equally randomized among four killing times (d 0, 7, 14 and 21), and one of
      two diets, a control and the UCNF. Diets contained comparable levels of protein,
      fat, and nonstructural carbohydrate and met 100% of the energy requirements of
      the pig. Intake and body weight were recorded daily while blood, urine and tissue
      samples were collected at time of kill. Within 1 wk of ingestion of the UCNF, the
      composition of plasma phospholipid fatty acids showed an increase in 20:5(n-3)
      and 22:6(n-3) (P < 0.0001) and a decrease in 20:4(n-6) and 18:2(n-6) (P <
      0.0001). Similar effects were observed for the phospholipids in the colonic and
      cecal mucosa. Plasma prostaglandin E was unaffected by treatment, whereas
      thromboxane B2 and 6-keto-prostaglandin F1 alpha levels were significantly
      decreased after 7 d of UCNF ingestion. Ingestion of the UCNF resulted in a
      suppression in the synthesis of proinflammatory prostaglandins by cecal and
      colonic mucosal cells. Levels of colonic and cecal prostaglandin E, 6-keto
      prostaglandin F1 alpha and thromboxane B2 were significantly decreased after 7 d
      of UCNF ingestion. These changes may have been mediated by rapid increases of (n
      3) fatty acids into cellular phospholipids. Dietary supplementation with the UCNF
      may prove beneficial for patients with ulcerative colitis by modulating colonic
      prostaglandin synthesis.

PMID- 9040558
TI  - The majority of dietary linoleate in growing rats is beta-oxidized or stored in
      visceral fat.
AB  - On a quantitative, whole-body basis, little is known about the amount of
      linoleate that is converted to arachidonate or the partitioning of linoleate and
      its longer-chain derivatives among lean and fat tissues. The aim of the present
      study was to examine linoleate balance and organ partitioning in rats consuming a
      low but adequate level of linoleate. Weanling male Sprague-Dawley rats were given
      free access to a semipurified diet containing 2.3% of energy as linoleate. Food
      intake, fecal output and body weight gain were measured for 26 d. Whole-body
      fatty acid balance analysis showed that 75.5% of the linoleate consumed
      disappeared (apparently by beta-oxidation), 18.7% was accumulated as linoleate,
      3.0% was converted to (n-6) longer-chain polyunsaturated fatty acids, and 1.2%
      was excreted in the feces Visceral fat contained 64% of the accumulated
      linoleate, and 23% was in lean tissues. Comparable values for alpha-linolenate
      were as follows: disappearance (84.9%), accumulation (10.9%), excretion in the
      feces (2.2%), and conversion to (n-3) longer-chain polyunsaturated fatty acids
      (1.4%). Visceral fat contained 67% of the accumulated alpha-linolenate, and 23%
      was in lean tissues. Visceral fat also accumulated 26% of newly synthesized (n-6)
      longer-chain polyunsaturated fatty acids and 31% of the (n-3) longer-chain
      polyunsaturated fatty acids. Thus, only 6.5% of dietary linoleate consumed at a
      low but adequate level for rats appeared in lean tissues as linoleate or its
      fatty acid metabolites; the rest was beta-oxidized or stored in fat, mostly in
      visceral fat. These results lead us to speculate whether losses through beta
      oxidation contribute to the recommended intake for linoleate in growing rats.

PMID- 9040559
TI  - Lipid metabolism is altered by nebacitin in rats fed cooked-stored polished rice
      as the only dietary carbohydrate with or without exogenous cholesterol.
AB  - Male adult Wistar rats were randomly divided into four groups in a 2 x 2
      factorial design and were fed diets containing cooked-stored polished rice
      (CSPR), with and without 0.7 g/100 g of Nebacitin [bacitracinneomycin sulfate
      (2:1, wt/wt)] and with and without 1 g cholesterol/100 g diet. The CSPR diet
      contained 1.87 g resistant starch/100 g. After 4 wk, arterial blood and liver
      were collected. Feces were collected during the last 7 d. Rats fed the diet with
      Nebacitin and cholesterol had higher serum total cholesterol than the rats fed
      diets without cholesterol. Serum triglyceride concentration was greater in rats
      fed Nebacitin, regardless of dietary cholesterol concentration. Rats fed the diet
      with Nebacitin and cholesterol had higher serum LDL cholesterol concentration and
      liver total cholesterol concentration than rats fed the other three diets. Rats
      fed the CSPR diet with Nebacitin both with and without cholesterol had a higher
      fecal resistant starch concentration and excretion and lower serum short-chain
      fatty acid concentration than rats fed the diets without Nabacitin. Hepatic
      cholesterol concentration was greater in rats fed Nebacitin only when the diet
      also contained cholesterol. Therefore, dietary Nebacitin alters lipid metabolism
      in rats, and some effects are most pronounced in those also fed cholesterol.

PMID- 9040560
TI  - Dietary L-glutamine supplementation reduces the growth of the Morris Hepatoma
      7777 in exercise-trained and sedentary rats.
AB  - Dietary glutamine supplementation and exercise have been reported independently
      to enhance immune function and reduce tumor growth. We study the effect of both
      of these interventions on the growth of the Morris Hepatoma 7777, implanted in 59
      female Sprague-Dawley Buffalo rats. Rats were fed a nutritionally complete,
      purified diet with or without L-glutamine 20 g/kg diet and randomized to swim 3
      h/d or to remain sedentary. After 14 d, the mean tumor weight of glutamine
      supplemented rats was lower (P < 0.0001) than that of unsupplemented rats (5.8 +/
      0.4 vs. 8.7 +/- 0.5 g, respectively). Exercise did not alter tumor growth.
      Glutamine supplementation increased [3H] thymidine incorporation by splenocytes
      incubated with Concanavalin A and the proportion of natural killer cells in
      spleen, but not cytotoxic activity against YAC-1 cells. Glutamine supplementation
      did not alter glutamine concentrations in plasma (691 +/- 12 mumol/L) or soleus
      muscle (5328 +/- 102 pmol/mg) but resulted in higher (P < 0.004) plasma
      concentrations of leucine, isoleucine and valine, precursors of glutamine.
      Splenocytes from exercised rats had a higher (P < 0.001) mitogen response than
      those from sedentary rats. Isolated tumor cells demonstrated high rates of non
      oxidative glucose and glutamine metabolism and consumption of glutamine,
      tryptophan and methionine. However, neither diet nor exercise significantly
      affected glucose or glutamine metabolism by tumor cells. The precise mechanism of
      tumor growth suppression by oral glutamine supplementation is not clear but may
      be related to changes in substrate availability, improved tumor-directed natural
      killer cytotoxic activity or a faster response to an immune challenge.

PMID- 9040561
TI  - Minimum thiamin requirement of weanling Sprague-Dawley outbred rats.
AB  - To determine the minimum thiamin requirement for maximal growth, two trials were
      conducted using male weanling Sprague-Dawley rats fed graded doses of thiamin
      from thiamin mononitrate as a component of a chemically defined diet. This diet
      included 16% amino acids, 72% sucrose and cornstarch and 5% soybean oil. Total
      weight gain and food intake were recorded over 2- (trial 1) or 3- (trial 2) wk
      periods. In trial 1, graded levels of thiamin were fed at 0, 0.5, 1.0, 2.0, 3.0,
      4.0 and 5.0 mg thiamin/kg diet, and growth rate reached a plateau in rats fed
      0.50 mg thiamin/kg. In trial 2, lower doses of thiamin were fed (0, 0.25, 0.50,
      0.75, 1.0, 4.0 and 5.0 mg/kg) to determine the minimum requirement for maximal
      growth. Using broken-line least-squares analysis, weight gain reached a plateau
      (6.8 g/d) at a thiamin concentration of 0.55 +/- 0.07 mg/kg. No differences (P >
      0.05) in weight gain, food intake or gain:food ratio were observed at thiamin
      levels at or above 0.5 mg/kg, but food intake was substantially lower (P < 0.05)
      in rats fed 0 and 0.25 mg thiamin/kg (9.9 and 13.4 g/d, respectively) than in
      rats fed higher doses of thiamin (16.1 g/d). Hepatic transketolase, a measure of
      enzymatic thiamin status, increased with dietary thiamin in rats fed diets
      containing 0-5.0 mg/kg thiamin. However, an inflection point occurred at 0.53 mg
      thiamin/kg, with the slope being eight times greater below than above the
      inflection point. The data suggest that the thiamin requirement for maximal
      growth of weanling rats fed a chemically defined diet is approximately 0.55 mg
      thiamin/kg, which is substantially below the current National Research Council
      estimated requirement of 3.1 mg thiamin/kg diet.

PMID- 9040562
TI  - Sodium mercaptoacetate is not a useful probe to study the role of fat in
      regulation of feed intake in dairy cattle.
AB  - Inhibition of fatty acid oxidation by mercaptoacetate stimulates food intake of
      rats fed dietary fat. To study regulation of feed intake of ruminants fed fat,
      dry matter intake and plasma concentrations of insulin and metabolites were
      determined in eight nonpregnant Holstein heifers in a cross-over design with two
      14-d feeding periods by using a 2 x 2 factorial arrangement of treatments.
      Treatments were combinations of diet (27 or 103 g fatty acids/kg food dry matter)
      and injection (mercaptoacetate or saline). Half the heifers were fed each diet in
      Period 1, and diets were reversed in Period 2. On d 10 of each period, two
      animals per treatment were injected intravenously with either mercaptoacetate
      (300 mumol/kg body weight 0.75) or saline at 2 h postfeeding. Injections were
      reversed on d 12. Dry matter intake was suppressed by the high fat diet.
      Intravenous injection of mercaptoacetate decreased dry matter intake to 25% that
      of the control during 4 h postinjection. Both the high fat diet and
      mercaptoacetate injection increased plasma non-esterified fatty acid
      concentration, whereas plasma beta-hydroxybutyrate concentration was lowered by
      the high fat diet and by mercaptoacetate injection. Plasma triglyceride
      concentration was increased by the high fat diet, but was decreased by
      mercaptoacetate injection. Mercaptoacetate elevated plasma glucose concentrations
      at 2 and 3 h postinjection, possibly because plasma insulin concentration was
      lower. Effects of mercaptoacetate on plasma insulin and metabolite concentrations
      may have been confounded by the effects of decreased feed intake. Therefore,
      direct effects of mercaptoacetate injection were not separated from effects of
      feed intake on plasma insulin and metabolite concentration. Because
      mercaptoacetate injection decreased dry matter intake it was not a useful probe
      to study mechanisms of feed intake regulation in dairy cattle fed fat.

PMID- 9040563
TI  - Iron uptake by isolated human enterocyte suspensions in vitro is dependent on
      body iron stores and inhibited by other metal cations.
AB  - The uptake of 59Fe ascorbate by suspensions of human enterocytes prepared from
      endoscopically derived duodenal biopsies was studied, with each subject's serum
      ferritin concentration determined at the time of endoscopy. Iron uptake was
      greatest at 37 degrees C. Uptake increased from pH 5.5 to 7.3, before being
      totally inhibited at pH 9.0. However, ferrous ion concentration, determined by 3
      (2-Pyridyl)-5,6-bis(4-phenyl sulfonic acid)-1,2,4-triazine, was greatest at pH
      5.5 and fell over this pH range. The rate of uptake was significantly greater by
      enterocytes isolated from individuals with a low serum ferritin (< 22 ng/L)
      compared with those with normal serum ferritin (> 22 ng/L). Vmax +/- (SEM) was
      78.7 +/- 8.5 pmol Fe/(micrograms DNA.min) in the normal group (n = 12) and 141 +/
      17.2 pmol Fe/(micrograms DNA.min) in the low ferritin group (n = 4, P < 0.008).
      Corresponding Km values were 52.5 +/- 11.7 and 66.7 +/- 5.1 mumol/L, respectively
      (P < 0.91). Zinc, lead, cobalt and manganese added to the incubation buffer
      significantly lowered iron uptake into cells (unselected patients). The
      concentrations of each metal required to halve the uptake rate from 50 mumol/L
      iron (IC50) were 85 +/- 5 mumol/L (Zn), 570 +/- 170 mumol/L (Pb), 1.1 +/- 0.1
      mmol/L (Co), and 3.8 +/- 0.7 mmol/L (Mn). The results demonstrate that
      enterocytes isolated by this method show the characteristics of iron uptake seen
      in animal studies. We suggest that these cells will be useful in the study of
      iron uptake in humans.

PMID- 9040564
TI  - Arachidonic acid offsets the effects on mouse brain and behavior of a diet with a
      low (n-6):(n-3) ratio and very high levels of docosahexaenoic acid.
AB  - This study investigated the effects of varying dietary levels of very long-chain
      polyunsaturated fatty acids on growth, brain fatty acid composition and behavior
      in mice. Five groups of pregnant and lactating B6D2F1 mice were fed diets with
      either a very high (n-6):(n-3) ratio of 49 [(n-3) deficient)], a normal ratio of
      4.0 or a low ratio of 0.32. The (n-6) fatty acids (FA) were provided either
      entirely as linoleic acid (LA) or as LA in combination with arachidonic acid
      (ARA), and the (n-6):(n-3) ratios were adjusted by partial replacement of the (n
      6) FA with docosahexaenoic acid (DHA). Offspring were maintained on these diets
      after weaning. The diets with the low (n-6): (n-3) ratio had no effect on the
      birth weights of the pups, but after 15 d resulted in a significant 12% reduction
      in body weights. This effect persisted to adulthood and was apparent in both
      brain and body weights unless ARA was substituted partially for LA as the source
      of (n-6) FA. There were significant effects of diet on brain fatty acid
      composition. Increasing levels of DHA in the diet increased brain DHA and
      decreased ARA, and there was also retroconversion of DHA in EPA in the mice fed
      high levels of DHA. Addition of ARA to the diet increased brain ARA, and, at high
      levels only, decreased DHA. There were no effects of this wide variation in
      dietary (n-6):(n-3) ratio on the ability of the mice to learn the place of the
      hidden platform in the Morris water maze. However, in both the cued and the place
      learning, the mice fed the low (n-6):(n-3) diet swam more slowly, unless ARA
      substituted partially for LA as the source of (n-6) FA. There were no effects of
      diet on activity in the spatial open field. These findings show that the effects
      of a diet with a low (n-6):(n-3) ratio and (n-3) FA provided as DHA, can be
      overcome if LA is partially replaced by ARA as the source of (n-6) FA.

PMID- 9040565
TI  - Methionine and 2-hydroxy-4-methylthiobutanoic acid transport.

PMID- 9040566
TI  - The prostate question, unanswered still.

PMID- 9040568
TI  - Nasogastric enteral feeding in hyperemesis gravidarum.

PMID- 9040567
TI  - Lipid metabolism and APC: implications for colorectal cancer prevention.

PMID- 9040569
TI  - Use of spacers with metered dose inhalers.

PMID- 9040570
TI  - Curvaceous model of recovery from depression.

PMID- 9040571
TI  - A unique case of frozen sperm export?

PMID- 9040572
TI  - "Euro-oncocredit" moves nearer.

PMID- 9040573
TI  - Use of antipolymer antibody assay in recipients of silicone breast implants.
AB  - BACKGROUND: Local complications (encapsulation, rashes, rupture, and leakage) can
      occur after placement of silicone gel-containing breast implants (SBI). Whether
      SBI exposure results in systemic manifestations in some recipients is
      controversial. We have carried out a blinded study to assess whether there is any
      difference between SBI recipients and non-exposed controls in the proportions
      positive for serum antibodies directed against polymeric substances. METHODS: We
      recruited female SBI recipients (including those without symptoms) who presented
      to a single rheumatology clinic. A physician global assessment was used to
      classify SBI recipients who did not meet criteria for specific autoimmune
      diseases according to the severity of local and systemic signs and symptoms.
      Controls were recruited from among clinic staff and their acquaintances. Results
      of the antipolymer antibody (APA) assay were compared with those of an assay for
      antinuclear antibodies (ANA) and with the severity of the signs and symptoms.
      FINDINGS: Positive APA results were found in one (3%) of 34 SBI recipients with
      limited symptoms, two (8%) of 26 with mild symptoms, seven (44%) of 16 with
      moderate symptoms, and 13 (68%) of 19 with advanced symptoms. Four (17%) of 23
      healthy non-SBI-exposed controls and two (10%) of 20 non-exposed women with
      classic autoimmune diseases were positive for APA. Thus, women with moderate or
      advanced symptoms were significantly more likely than those with limited or mild
      symptoms, or non-exposed controls to have APA (p < 0.001). The proportion with
      positive ANA results was higher for women with classic autoimmune diseases 14
      (70%) of 20 than for any SBI-exposed subgroup (0-33%). INTERPRETATION: The APA
      assay can objectively contribute to distinguishing between SBI recipients with
      limited or mild signs and symptoms. SBI recipients with more severe
      manifestations, and patients with specific autoimmune diseases. Further studies
      will be needed to define the signs and symptoms associated with exposure to SBI.

PMID- 9040574
TI  - Blood-pressure control in the hypertensive population.
AB  - BACKGROUND: In large-scale surveys of individuals with hypertension those whose
      clinic blood pressure is reduced to 140/90 mm Hg or less have been found to
      represent only a small fraction of the hypertensive population. We assessed
      whether these results arise because of a white-coat effect elevating clinic blood
      pressure. METHODS: We randomly selected 2400 individuals from the town of Monza,
      Italy, and invited them to take part in our study. We measured clinic blood
      pressure as well as home (morning and evening measurements), and 24 h ambulatory
      blood pressure-ie, blood pressures largely devoid of a white-coat effect. Based
      on clinic blood pressure participants were then classified as normotensive,
      untreated hypertensive (clinic blood pressure > 140 mm Hg systolic and/or > 90 mm
      Hg diastolic), or treated hypertensive (having antihypertensive treatment). The
      mean blood pressures for each group were calculated. FINDINGS: 1651 people took
      part in the study. The clinic blood pressure of treated hypertensives (n = 207;
      146.9 [SD 18] mm Hg/90.2 [8.6] mm Hg) was only slightly less than in untreated
      hypertensives (n = 402; 148 [15.2] mm Hg/93.3 [8] mm Hg) and in both groups the
      blood pressure values were much greater than those of normotensive individuals (n
      = 1042; 119.5 [10.3] mm Hg/78.1 [6.6] mm Hg) p < 0.001. Averaged home and 24 h
      blood pressures were lower than clinic blood pressures but similarly higher in
      untreated and treated hypertensive individuals when compared with normotensive
      individuals. This was also the case for day and night average blood pressures.
      The number of treated hypertensive patients found to have blood pressures within
      the normal limits was small not only when based on clinic blood pressure values
      but also when based on ambulatory blood-pressure values. INTERPRETATION: In the
      hypertensive population the number of patients with inadequate blood-pressure
      control is high not only when assessed in the clinic but also when assessed by
      ambulatory-blood-pressure monitoring or at home. The high blood-pressure values
      commonly found in treated hypertensive individuals cannot be accounted for by a
      white-coat effect but by a true lack of daily-life blood-pressure control.

PMID- 9040575
TI  - Risk of endometrial cancer in relation to use of oestrogen combined with cyclic
      progestagen therapy in postmenopausal women.
AB  - BACKGROUND: Postmenopausal oestrogen therapy reduces the risk of osteoporosis and
      cardiovascular diseases but is associated with an increased risk of endometrial
      cancer. We have assessed the impact of a regimen of oestrogen with cyclic
      progestagen on risk of endometrial cancer for postmenopausal women. METHODS: We
      did a population-based case-control study of women aged 45-74 years in western
      Washington State, USA. Cases were identified from a regional cancer registry as
      having histologically confirmed endometrial cancer during 1985-91. 832 (72%) of
      1154 eligible cases completed interviews. Controls were identified by random
      digit dialling, screened for intact uterus, frequency matched for age and county,
      and randomly assigned a reference date within 1985-91. Interviews with 1114 (73%)
      of 1526 eligible controls were done. The women provided information about use of
      hormone replacement therapy, and reproductive and medical history before
      diagnosis date (cases) or reference date (controls). FINDINGS: Relative to women
      who had never used hormones (for > 6 months), women who had taken unopposed
      oestrogen had a four-fold increase (95% CI 3.1-5.1) in risk of endometrial
      cancer. Women who used a combined therapy of oestrogen with cyclic progestagen
      (eg. medroxyprogesterone acetate) had a relative risk of 14 (1.0-1.9). Among
      women with fewer than 10 days of added progestagen per month, the relative risk
      was 3.1 (1.7-5.7). Whereas that for women with 10-21 days of added progestagen
      was 1.3 (0.8-2.2). The use of these combined regimens for 5 or more years was
      associated with risks of 3.7 (1.7-8.2) and 2.5 (1.1-5.5), respectively, relative
      to non-users of hormones. INTERPRETATION: Postmenopausal women who use combined
      therapy of oestrogen with cyclic progestagen on a long-term basis have an
      increased risk of endometrial cancer compared with those who are not on hormone
      replacement, even when progestagen is added for 10 or more days per month. This
      increase is much smaller than that associated with unopposed oestrogen, but needs
      to be confirmed.

PMID- 9040576
TI  - Production of C-reactive protein and risk of coronary events in stable and
      unstable angina. European Concerted Action on Thrombosis and Disabilities Angina
      Pectoris Study Group.
AB  - BACKGROUND: Inflammation is an important feature of atherosclerotic lesions, and
      increased production of the acute-phase reactant. C-reactive protein (CRF), is
      associated with a poor prognosis in severe unstable angina. We have investigated
      the existence and possible significance of the acute-phase responses of CRP and
      another sensitive reactant, serum amyloid A protein (SAA), in patients with
      unstable or stable angina. METHODS: We used new ultrasensitive immunoassays to
      measure CRP and SAA concentrations in plasma from 2121 outpatients with angina
      (1030 unstable, 743 stable, the rest atypical) enrolled in the European Concerted
      Action on Thrombosis and Disabilities (ECAT) Angina Pectoris Study. All patients
      underwent coronary angiography and extensive clinical and laboratory assessment
      at study entry, and were then followed up for 2 years. All suspected coronary
      events during follow-up were reviewed by an independent endpoint committee.
      FINDINGS: 75 individuals (41 with unstable, 29 with stable, and 5 with atypical
      angina) had a coronary event during follow-up. Concentrations of CRP at study
      entry were associated with coronary events in patients with stable or unstable
      angina: there was about a two-fold increase in the risk of a coronary event in
      patients whose CRP concentration was in the fifth quintile (> 3.6 mg/L), compared
      with the first four quintiles. A third of the events occurred among patients who
      had a CRP concentration of more than 3.6 mg/L. CRP concentrations were positively
      correlated with age, smoking, body-mass index, triglycerides, extent of coronary
      stenosis, history of myocardial infarction, and lower ejection fraction. By
      contrast, concentrations of SAA were not associated with risk of a coronary
      event. INTERPRETATION: We found that raised circulating concentrations of CRP are
      predictors of coronary events in patients with stable or unstable angina. The
      modest acute-phase responses of CRP were probably not the result of myocardial
      necrosis. Whatever the underlying mechanisms, the sensitive measurement of CRP as
      a prognostic marker may be useful in the management of coronary heart disease.

PMID- 9040577
TI  - Extracorporeal support for intractable cardiorespiratory failure due to
      meningococcal disease.
AB  - BACKGROUND: Meningococcal disease is still associated with considerable
      mortality, despite the use of early antibiotics and management in specialised
      intensive care units, due principally to early refractory myocardial depression
      and hypotension as well as severe acute respiratory distress syndrome.
      Extracorporeal membrane oxygenation (ECMO) is a complex technology that uses a
      modified "heart-lung" machine to provide temporary cardiac and respiratory
      support. We reviewed the UK and Australian experience of the use of ECMO in
      patients with refractory cardiorespiratory failure due to meningococcal disease.
      METHODS: The records from all 12 known patients supported with ECMO for
      meningococcal disease in the UK and Australia since 1989 were reviewed. FINDINGS:
      12 patients (aged 4 months to 18 years, median 26 months) with meningococcal
      disease received ECMO over 8 years. In seven patients, ECMO was required early
      for cardiac support for intractable shock within 36 h of admission to intensive
      care. In the other five patients, ECMO was indicated for respiratory failure due
      to severe adult respiratory distress syndrome, which tended to occur later in the
      disease. The paediatric risk of mortality score ranged from 13 to 40 (median 29,
      median predicted risk of mortality 72%). Six of the 12 patients required
      cardiopulmonary resuscitation before ECMO and the other six were deteriorating
      despite maximal conventional therapy. Overall, eight of the 12 patients survived,
      with six leading functionally normal lives at a median of 1 year (range 4 months
      to 4 years) of follow-up. INTERPRETATION: ECMO might be considered to support
      patients with intractable cardiorespiratory failure due to meningococcal disease
      who are not responding to conventional treatment.

PMID- 9040578
TI  - Severe encephalitis with rapid recovery.

PMID- 9040579
TI  - Familial adenomatous polyposis presenting with childhood desmoids.

PMID- 9040580
TI  - Breast screening programme: should the interval between tests depend on age?

PMID- 9040581
TI  - Infant mortality and the incidence of inflammatory bowel disease.

PMID- 9040582
TI  - Crohn's disease and measles.

PMID- 9040583
TI  - Defective homocysteine metabolism as a risk factor for diabetic retinopathy.

PMID- 9040584
TI  - Neutropenia with ticlopidine plus aspirin.

PMID- 9040585
TI  - Peripheral blood stem-cell transplantation for refractory autoimmune
      thrombocytopenic purpura.

PMID- 9040586
TI  - Interleukin-1 receptor antagonist gene in multiple sclerosis.

PMID- 9040587
TI  - 12-year follow-up of allogeneic bone-marrow transplant for Langerhans' cell
      histiocytosis.

PMID- 9040588
TI  - Increase reported in UK HIV-1 infections in 1996.

PMID- 9040589
TI  - Pancreatic carcinoma.

PMID- 9040590
TI  - Chemokines: leucocyte recruitment and activation cytokines.
AB  - Chemokines are a family of structurally related proteins that share the ability
      to induce migration of specific subsets of leucocytes. These specialised
      cytokines play a critical part in the generation of cellular inflammation, both
      in the protective responses to invading pathogens and in the pathological
      processes associated with infection and immune-mediated diseases. Chemokines are
      more than simple chemotactic factors, since they are also implicated in leucocyte
      activation, angiogenesis, and antimicrobial functions, including a protective
      role in HIV infection. These molecules provide potentially valuable targets for
      therapeutic intervention in a wide range of diseases.

PMID- 9040591
TI  - Ethically justified, clinically comprehensive guidelines for percutaneous
      endoscopic gastrostomy tube placement.
AB  - Guidelines for the placement of percutaneous endoscopic gastrostomy (PEG) tubes
      are not available. We developed a decision-making algorithm by integrating the
      medical and ethical dimensions of the decision. According to our algorithm,
      physicians should not offer PEG tubes to patients with anorexia-cachexia
      syndromes. For patients with permanent vegetative states, physicians should offer
      and recommend against the procedure. For patients who have dysphagia without
      other deficits in quality of life, physicians should offer and recommend the
      procedure. For the the remaining patients who have dysphagia with other deficits
      in quality of life, the physician's role is to provide non-directive counselling
      regarding the short and long-term consequences of a trial of PEG tube feeding.

PMID- 9040592
TI  - HIV: the other dimension.

PMID- 9040593
TI  - Birthweight as risk factor for breast cancer.

PMID- 9040594
TI  - Birthweight as risk factor for breast cancer.

PMID- 9040595
TI  - Birthweight as risk factor for breast cancer.

PMID- 9040596
TI  - Birthweight as risk factor for breast cancer.

PMID- 9040597
TI  - Escherichia coli O157: outbreak in central Scotland.

PMID- 9040598
TI  - 3D-mapping of pressure sores.

PMID- 9040599
TI  - Tissue-plasminogen activator for acute ischaemic stroke.

PMID- 9040600
TI  - Tissue-plasminogen activator for acute ischaemic stroke.

PMID- 9040601
TI  - Is detrusor instability a prematurely activated (but otherwise normal)
      micturition reflex?

PMID- 9040602
TI  - The Fracture Intervention Trial.

PMID- 9040603
TI  - Occupation, fibrinogen, and heart disease.

PMID- 9040604
TI  - Dietary salt and renal stone disease.

PMID- 9040605
TI  - Dietary salt and renal stone disease.

PMID- 9040606
TI  - Medicine in Germany.

PMID- 9040607
TI  - Medicine in Germany.

PMID- 9040608
TI  - Medicine in Germany.

PMID- 9040609
TI  - Declining cancer mortality in European Union.

PMID- 9040610
TI  - Balloon ripening of the cervix.

PMID- 9040611
TI  - Use of unlicensed nitric oxide in Austria.

PMID- 9040612
TI  - The politics of disclosure.

PMID- 9040613
TI  - Mercurial atavism.

PMID- 9040614
TI  - Practitioner or provider: are they mutually exclusive?

PMID- 9040615
TI  - Cricopharyngeal myotomy for neurogenic oropharyngeal dysphagia.
AB  - BACKGROUND: Forty patients (18 women, 22 men) with incapacitating oropharyngeal
      dysphagia of neurologic origin underwent cricopharyngeal myotomy. The subjective
      and objective response to myotomy was analyzed retrospectively with a mean
      postoperative follow-up of 48 months (range 1 to 255 months). RESULTS: Radiologic
      evidence of functional obstruction caused by incoordination and incomplete
      relaxation of the upper esophageal sphincter was significantly reduced.
      Manometric recordings of resting and closing pressures of the upper esophageal
      sphincter were also significantly altered by the myotomy. Resting pressures
      decreased from 65 to 18 mm Hg and closing pressures dropped from 69 to 22 mm Hg.
      The relaxation time and poor coordination at the level of the upper esophageal
      sphincter, observed in the preoperative period, persisted after the operation.
      Radionuclide emptying studies in which a single liquid bolus was used showed
      persistent hypopharyngeal stasis with a 20% retention of radioactive material at
      120 seconds. Subjectively, 33 patients initially had frequent aspiration
      episodes. Twenty became free of symptoms after myotomy (p < 0.01) and in six
      others the symptoms were improved. Overall, seven patients claimed to be free of
      symptoms of dysphagia and no longer had pharyngo-oral or pharyngonasal
      regurgitations and aspirations after their operation. Twenty-three other patients
      had improvement in symptoms. Ten patients reported no change in symptoms. All of
      them either were unable to swallow voluntarily or had dysarthria when assessed
      before the operation. One retropharyngeal hematoma is the only postoperative
      complication recorded. The operative mortality was 2.5% (1/40). CONCLUSIONS:
      Cricopharyngeal myotomy palliates neurogenic oropharyngeal dysphagia in patients
      with intact oral-phase deglutition.

PMID- 9040616
TI  - Aggressive surgical management of sternoclavicular joint infections.
AB  - BACKGROUND: Although the sternoclavicular joint is an unusual site for infection,
      thoracic surgeons may preferentially be called on to coordinate management of
      cases refractory to antibiotic therapy because of the anatomic relationship of
      this joint to major vascular structures. METHODS: Since 1994 we have surgically
      managed nine sternoclavicular joint infections in eight patients. Associated
      medical problems were frequent and included diabetes mellitus (n = 2), end-stage
      renal disease (n = 2), hematologic disorders (n = 2), and multiple joints
      affected by sepsis (n = 4). Open joint exploration with drainage and debridement
      with the use of general anesthesia was performed in four patients. The remaining
      four patients (one with bilateral sternoclavicular joint infections) had computed
      tomographic evidence of diffuse joint and surrounding bone destruction with
      infection extending into mediastinal soft tissues. Surgical therapy for these
      five joint infections involved en bloc resection of the sternoclavicular joint
      with an ipsilateral pectoralis major muscle covering the bony defect. RESULTS:
      There were two deaths unrelated to the surgical procedure. After a mean follow-up
      of 20 months, the remaining six survivors (seven joints) have complete healing
      with no apparent limitation in the range of motion even after en bloc resection.
      CONCLUSIONS: Most cases of early sternoclavicular joint infections will respond
      to conservative measures. However, when radiographic evidence of infection beyond
      the sternoclavicular joint is present, en bloc resection, although seemingly
      aggressive, results in immediate eradication of all infection with negligible
      functional morbidity. Prolonged antibiotic therapy or continued local drainage
      procedures appear to have little value in these cases, adding only to patient
      care costs and the potential sequelae of chronic infections.

PMID- 9040617
TI  - Mediastinal lymph node metastasis in patients with clinical stage I peripheral
      non-small-cell lung cancer.
AB  - Our aim in this study was to determine the mediastinal areas where
      lymphadenectomy should be done at the time of surgical resection of clinical
      stage I lung cancer. Between 1984 and 1994, 575 patients with clinical stage I
      non-small-cell lung cancer underwent lobectomy and systematic mediastinal
      lymphadenectomy. Mediastinal lymph nodes were pathologically positive for disease
      in 79 patients (14%), and positive nodes appeared normal intraoperatively in 54
      patients (68%). Thirty-three percent of those patients with positive N2
      (mediastinal) nodes had negative lobar (N1) nodes. In cancer of the right upper
      lobe, all N2 cases had the lymph node metastases in the superior mediastinal
      compartment. In cancer of the right middle lobe, all N2 cases but one had the
      metastases in subcarinal or anterior mediastinal nodes. In cancer of the right
      lower lobe, all N2 cases but one the metastases in subcarinal nodes. In cancer of
      the left upper lobe, all N2 cases had the lymph node metastases in the subaortic
      compartment. In cancer of the left lower lobe, all N2 cases but one had the lymph
      node metastases in the subcarinal area or subaortic compartment. In conclusion,
      systematic staging of mediastinal lymph nodes is necessary for all patients with
      resectable clinical stage I lung cancer. The location of the primary tumor
      determines the mediastinal areas where lymphadenectomy should be done to examine
      all lymph nodes.

PMID- 9040619
TI  - Modified Fontan procedure in ninety-nine cases of atrioventricular valve
      regurgitation.
AB  - Between January 1985 and August 1995, among 242 patients who underwent a modified
      Fontan procedure, 99 had atrioventricular valve regurgitation ranging in degree
      from 1 to 4, for which concomitant repair of the atrioventricular valve
      regurgitation was done in the majority of cases. In all but 4 cases the
      atrioventricular valve was repaired mainly by circular annuloplasty and valve
      replacement was not done in any case. Although the hospital mortality rate was
      significantly higher in cases with atrioventricular valve regurgitation (12/99,
      12%) than in cases without (4/143, 3%; p < 0.0037, chi 2 test), actuarial
      survival in atrioventricular valve regurgitation was 84% for years 5 through 10.
      The degree of atrioventricular valve regurgitation before operation was 1.6 +/-
      0.7 on average: in 49 cases with higher than grade 2 regurgitation before
      operation there was a significant decrease to 0.4 +/- 0.49 (p < 0.0001) after
      operation in short-term survivors. Patients with atrioventricular valve
      regurgitation can be treated with reasonable risk, provided proper repair of the
      valve is done. Circular annuloplasty is a simple and uniformly effective method
      to control regurgitation even in cases of common atrioventricular valve.

PMID- 9040618
TI  - Anatomic correction of the syndrome of prolapsing right coronary aortic cusp,
      dilatation of the sinus of Valsalva, and ventricular septal defect.
AB  - BACKGROUND: Although the syndrome of ventricular septal defect and aortic
      regurgitation was described a long time ago, there is still no agreement about
      the anatomic and functional components of the syndrome and the optimal methods of
      management. OBJECTIVE: Our objective was to describe a new simple technique of
      anatomic correction of all the components of the syndrome, based on redefining
      the salient anatomic and functional features of the syndrome. METHODS: Anatomic
      correction of the syndrome is achieved through a transaortic approach with the
      placement of a series of pledget-supported mattress sutures using autogenous
      pericardium. The sutures are used to close the ventricular septal defect, plicate
      the aortic sinus, and correct the outward and downward displacement of the anulus
      of the aortic valve. The technique is designed to correct all the anatomic
      functional components including severe aortic regurgitation when present.
      RESULTS: Between 1972 and 1996, 46 patients with this syndrome underwent surgical
      treatment. The current technique was used in most of the patients operated on
      before 1981 and in all patients since that date. There were no early or late
      deaths during a follow-up period varying from 3 months to 24 years (mean 8.4
      years). Aortic regurgitation was abolished in 16 and improved in the remaining
      patients, The hemodynamic results have been maintained except in five patients
      operated on early in the series, in whom additional procedures on the cusps were
      performed. CONCLUSIONS: Anatomic correction of all the components of the syndrome
      of prolapsing right coronary cusp, dilatation of the sinus of Valsalva, and
      ventricular septal defect, can be achieved by a very simple technique. This
      technique can be applied in young children and prevents progression and secondary
      changes. Early correction in all patients with this syndrome is warranted.

PMID- 9040620
TI  - Maturation alters the pulmonary arterial response to hypoxia and inhaled nitric
      oxide in the presence of endothelial dysfunction.
AB  - Surgical intervention in ever younger patients has led to a new appreciation of
      the unique physiology of the neonate. Specifically, newborn patients may respond
      very differently to hypoxic episodes and subsequent treatment with inhaled nitric
      oxide than older infants. In the current study, we examined differences in the
      pulmonary arterial response to hypoxia and inhaled nitric oxide in 48-hour-old (n
      = 8) and 14-day-old (n = 8) Yorkshire pigs in a model of nitric oxide synthase
      inhibition, as might be seen with endothelial dysfunction. Data were acquired
      after treatment with the nitric oxide synthase inhibitor N omega-nitro-L-arginine
      during hypoxia (inspired oxygen fraction = 0.10) and during inhalation of nitric
      oxide (100 ppm). Input mean impedance, reflecting distal arteriolar
      vasoconstriction, and characteristic impedance, reflecting proximal arterial
      geometry and distensibility, were calculated. The modulus of elasticity, a
      measure of the "stiffness" of the proximal vessels, was also calculated. Hypoxia
      caused a large increase in input mean impedance in both 48-hour-old and 14-day
      old pigs (4826 +/- 272 versus 8744 +/- 488 dyne.cm.sec-5 and 3129 +/- 73 versus
      6000 +/- 134 dyne.cm.sec-5, respectively; p = 0.0078). Characteristic impedance
      was not altered in the younger animals (1171 +/- 76 dyne.cm.sec-5) but increased
      in the older animals (419 +/- 15 versus 797 +/- 20 dyne.cm.sec-5. p = 0.0078).
      Older animals also experienced an increase in the modulus elasticity (1.92E06 +/-
      3.2E05 versus 1.05E07 +/- 3.9E05 dyne/cm2, p = 0.0078). These data show that
      inhibited nitric oxide production, as might be seen in endothelial dysfunction,
      potentiates the profound hypoxic vasoconstriction observed at the level of the
      distal pulmonary arterioles in both neonatal and infant animals. In contrast,
      only older animals had a stiffening of the larger, more proximal vessels with
      hypoxia. In both age groups, inhaled nitric oxide effectively reduced the
      increases in impedance.

PMID- 9040621
TI  - Plasma neuropeptide Y and catecholamines in pediatric patients undergoing cardiac
      operations.
AB  - OBJECTIVE: Our objective was to assess the sympathoadrenal response in pediatric
      patients undergoing repair of congenital cardiac defects. METHODS: Plasma
      catecholamine (norepinephrine and epinephrine) and neuropeptide Y concentrations
      were quantified before and after cardiopulmonary bypass to assess the response to
      cardiopulmonary bypass. To determine the response to aortic occlusion, levels of
      plasma catecholamines and neuropeptide Y were measured at the time of and
      immediately after release of the aortic crossclamp. RESULTS: During
      cardiopulmonary bypass, no significant change in levels of plasma norepinephrine
      (n = 43), epinephrine (n = 37), or neuropeptide Y (n = 46) was observed. Aortic
      occlusion induced a significant increase in plasma neuropeptide Y, but not in
      catecholamines. There was a greater increase in plasma neuropeptide Y in children
      older than age 1 year than in those younger than 1 year. CONCLUSIONS: Plasma
      neuropeptide Y may be a useful marker of sympathetic nervous system activity.
      Children younger than age 1 year showed a lesser sympathetic response compared
      with the response in older children.

PMID- 9040622
TI  - Results of allograft aortic valve replacement for complex endocarditis.
AB  - METHODS: Between November 1985 and July 1995, 36 patients underwent allograft
      aortic valve replacement for endocarditis. The mean age of the 29 men and seven
      women was 53 years (range 25 to 79 years). Previous procedures included
      mechanical (n = 9), bioprosthetic (n = 5), and allograft (n = 2) aortic valve
      replacement, aortic valvotomy (n = 1), and orthotopic heart transplantation (n =
      1). Infecting organisms were Staphylococcus and Streptococcus species in 69% of
      patients and fungi in 6%. Intraoperative findings demonstrated valvular
      vegetations (n = 25), annular abscesses (n = 25), and cusp destruction (n = 13).
      Complex reconstruction of the aortic anulus was required in 25 patients, and
      associated procedures included mitral valve repair (n = 2), mitral valve
      replacement (n = 3), coronary artery bypass grafting (n = 8), repair of
      ventricular septal defect (n = 4), left ventricular aneurysmectomy (n = 1), and
      repair of atrial septal defect (n = 1). Allograft valve insertion was performed
      by the scalloped technique in seven, intraaortic cylinder technique in 19, and
      allograft aortic root replacement in 10. RESULTS: Follow-up was 100% complete at
      a mean of 2.6 +/- 2.8 years after valve replacement. Operative mortality was
      13.8%. Complications included low cardiac output (n = 10), bleeding (n = 2),
      myocardial infarction (n = 1), stroke (n = 1), renal insufficiency (n = 2),
      respiratory insufficiency (n = 3), and heart block (n = 8). Late echocardiogram
      (mean 2.6 +/- 1.8 years) demonstrated grade III/IV aortic regurgitation in five
      patients. There were seven late deaths (five cardiac, not valve-related; two
      noncardiac). No patient has had recurrence of endocarditis. Actuarial survival at
      5 years was 53.1% +/- 11.5%. Univariate analysis demonstrated prosthetic valve
      endocarditis to adversely affect late survival (p = 0.04). Cumulative risk of
      reoperation at 5 years was 8.0% +/- 5.6%. CONCLUSION: Allograft aortic valve
      replacement facilitated reconstruction of complex aortic valve endocarditis with
      a low reoperation rate and no recurrent endocarditis in this series.

PMID- 9040624
TI  - Viscoelasticity of dynamically fixed bioprosthetic valves. II. Effect of
      glutaraldehyde concentration.
AB  - OBJECTIVE: We have previously shown the benefits of dynamic fixation over
      conventional static fixation of bioprosthetic valves. In an attempt to increase
      the durability of bioprosthetic heart valves, we explored the benefit of low
      concentration glutaraldehyde dynamic fixation. METHODS: Pig aortic valves
      obtained fresh from the abattoir and excised with the entire root were
      dynamically fixed in glutaraldehyde phosphate buffer solutions varying in
      concentration from 0.05% to 2.5%. Denaturation temperatures were measured and
      mechanical testing was performed at low (3 mm/sec) to high physiologic rates (30
      mm/sec) at 37 degrees C in isotonic modified Hanks solution. RESULTS: When fixed
      dynamically in 0.05% glutaraldehyde solution for 24 hours, the tissue reached a
      degree of cross-linking (denaturation temperature = 82.8 degrees +/- 0.6 degree
      C) significantly higher than that obtained for 0.05% static fixation
      (denaturation temperature = 79.3 degrees +/- 0.9 degree C) (p < 0.05) but similar
      to that for conventional static fixation in 0.5% glutaraldehyde solution
      (denaturation temperature = 83.5 degrees +/- 0.3 degree C). After fixation in low
      concentration glutaraldehyde (0.05%), final relaxation slopes and moduli in the
      circumferential direction were significantly higher than those for the statically
      fixed tissue but similar to those for the fresh tissue. However, both dynamic and
      static fixation had the effect of increasing tissue extensibility to similar
      extents in both directions, irrespective of glutaraldehyde concentration.
      CONCLUSIONS: Dynamic glutaraldehyde fixation of a porcine aortic valve at lower
      concentrations resulted in a better degree of cross-linking and a material with
      biomechanical properties that more closely mimic those of natural heart valve
      tissue.

PMID- 9040623
TI  - Papillary muscle-left ventricular wall "complex".
AB  - OBJECTIVES: Mitral valve homografts, despite theoretical advantages, are not
      widely used, in part because of lack of basic information about the three
      dimensional geometry of the mitral apparatus. METHODS: Radiopaque markers were
      used in the study of eight closed-chest dogs under four conditions: (1) baseline,
      (2) caval occlusion, (3) tachycardia (atrial pacing), and (4) nitroprusside
      infusion. Using a cylindrical coordinate system. defined with the origin at the
      midpoint between the anterior and posterior commissures, and the left ventricular
      long axis (z-axis), defined by the origin and the left ventricular apex, DTIP-MA
      (the z-coordinate [millimeters] of the papillary muscle tip), was measured at 10
      time points throughout the entire cardiac cycle. DBASE-MA (the z-coordinate of
      the papillary muscle base) and LPM (the length of the papillary muscle
      [millimeters]) were also measured. RESULTS: DTIP-MA varied slightly with time (p
      < 0.001 by analysis of variance), but the magnitude of change was negligible (<
      0.9 mm) (e.g., DTIP-MA of the anterior papillary muscle was 20.7 +/- 2.7/20.8 +/-
      2.8 [end-diastolic/end-systolic, mean +/- 1 standard deviation]; DTIP-MA of the
      posterior papillary muscle was 25.8 +/- 4.8/25.5 +/- 4.5). DTIP-MA was minimally
      influenced by the above perturbations. DBASE-MA and LPM of each papillary muscle,
      however, changed throughout the cardiac cycle (p < 0.001 by analysis of variance)
      by about 4 mm, and both parameters were dependent on loading conditions.
      CONCLUSIONS: Papillary muscle length changed to keep the DTIP-MA distance
      constant such that the papillary muscle and left ventricular wall functioned
      together as a unit ("J-shaped complex"). These results provide a physiologic
      rationale for measuring DTIP-MA, define its potential surgical usefulness, and
      imply that using the entire length of the donor's papillary muscle (i.e.,
      maintaining the entire J-shaped complex) is important in operations in which
      homograft or stentless xenograft mitral valves are used.

PMID- 9040625
TI  - An analysis of valve re-replacement after aortic valve replacement with biologic
      devices.
AB  - Biologic valve re-replacement was examined in a series of 1343 patients who
      underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with
      a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve. A
      parametric model approach was used to simultaneously model the competing risks of
      death without re-replacement and re-replacement before death. One hundred eleven
      patients underwent a first re-replacement for a variety of reasons (69 patients
      with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and
      14 patients with cryopreserved allograft valves). By multivariable analysis
      younger age at operation was associated with xenograft, 4 degrees C stored
      allograft, and cryopreserved allograft valve re-replacement. However, this effect
      was examined in the context of longer survival of younger patients, which
      increases their exposure to the risk of re-replacement as compared with that in
      older patients whose decreased survival reduced their probability of requiring
      valve re-replacement. In patients older than 60 years at the time of aortic valve
      replacement, the probability of re-replacement (for any reason) before death was
      similar for xenografts and cryopreserved allograft valves but higher for 4
      degrees C stored valves. However, in patients younger than 60 years, the
      probability of re-replacement at any time during the remainder of the life of the
      patient was lower with the cryopreserved allograft valve compared with the
      xenograft valve and 4 degrees C stored allografts.

PMID- 9040626
TI  - Effect of aprotinin on vascular reactivity of coronary bypass grafts.
AB  - OBJECTIVE: Aprotinin reduces postoperative bleeding and the need for transfusion
      after cardiopulmonary bypass. The current clinical concern about aprotinin is
      that it may increase the incidence of postoperative graft thrombosis and
      thromboembolic phenomena. The fact that the mechanism of action of aprotinin is
      not completely elucidated and that its effects on the vascular reactivity of
      bypass conduits are unknown raise doubts regarding its safety. In an attempt to
      clarify these issues we investigated the vascular reactivity of the human
      saphenous vein and internal thoracic artery to a range of vasoconstrictor agents
      in the presence or absence of aprotinin. METHODS: Human saphenous vein was
      obtained from 24 patients and internal thoracic artery from 7 patients undergoing
      coronary artery bypass. Vessels were set up in organ baths to record changes in
      vessel wall tension. RESULTS: Endothelium-dependent relaxations to acetylcholine
      in saphenous vein rings were unaffected after aprotinin treatment. Contractions
      to the thromboxane analog U46619 were significantly attenuated after aprotinin
      treatment in the saphenous vein. Maximum responses were reduced from control
      values of 88 +/- 7.5 mN to 49.3 +/- 4.8 mN with 1 mumol/L doses of aprotinin (p <
      0.05) and 36.6 +/- 4.8 mN with 10 mumol/L doses of 5-hyroxytryptamine or
      noradrenaline after aprotinin incubations. Furthermore, contractions to U46619 in
      the internal thoracic artery were unaffected by aprotinin. CONCLUSION: Our data
      show that there is a preservation of endothelium-dependent responses to
      acetylcholine and a reduced U46619 vasoconstrictor action on the saphenous vein
      after aprotinin treatment. Thus the direct effect of aprotinin on the vessel wall
      could counteract the potential effect of its prothrombotic action on graft
      patency.

PMID- 9040627
TI  - Attenuation of lung graft reperfusion injury by a nitric oxide donor.
AB  - OBJECTIVE: One of the primary features of ischemia-reperfusion injury is reduced
      production of protective autocoids, such as nitric oxide, by dysfunctional
      endothelium. Administration of a nitric oxide donor during reperfusion of lung
      grafts may therefore be beneficial through modulation of vascular tone and
      leukocyte and platelet function. METHODS: Rat lung grafts were flushed with
      University of Wisconsin solution and reperfused for 1 hour in an ex vivo model
      incorporating a support animal. Group I grafts (n = 6) were reperfused
      immediately after explantation, group II (n = 6) and III (n = 5) grafts after 24
      hours of storage at 4 degrees C. In group III, glyceryl trinitrate, a nitric
      oxide donor, was administered during the first 10 minutes of reperfusion at a
      rate of 200 micrograms/min. In an additional group (n = 5), 200 micrograms/min
      hydralazine was administered instead, to assess the effect of vasodilation alone.
      RESULTS: Graft function in group II deteriorated compared with that in group I,
      with significant reduction of graft effluent oxygen tension and blood flow and
      elevation of pulmonary artery pressure, peak airway pressure, and wet/dry weight
      ratio. In contrast, in group III, glyceryl trinitrate treatment improved graft
      function to baseline levels in all these parameters. Administration of
      hydralazine, meanwhile, produced mixed results with only two out of five grafts
      functioning at control levels. CONCLUSIONS: In this model, administration of
      glyceryl trinitrate to supplement the nitric oxide pathway in the early phase of
      reperfusion has a sustained beneficial effect on lung graft function after 24
      hour hypothermic storage, probably through mechanisms beyond vasodilation alone.

PMID- 9040628
TI  - Treatment of refractory acute allograft rejection with aerosolized cyclosporine
      in lung transplant recipients.
AB  - Lung transplant recipients who have persistent acute cellular rejection are at
      increased risk for the development of chronic rejection, the leading cause of
      reduced long-term survival. This study evaluated the use of aerosolized
      cyclosporine as rescue therapy for unremitting acute rejection. Between June 1993
      and March 1996, 18 patients with rejection that failed to resolve after therapy
      with pulse steroids and antilymphocyte globulin were enrolled in the study.
      Aerosolized cyclosporine A (300 mg) treatment was initiated for 10 consecutive
      days followed by a maintenance regimen of 3 days per week. Efficacy was assessed
      by graft histologic and pulmonary function testing. With the use of linear
      regression, results in these patients were compared with those in 23 control
      patients, matched for histologic acute rejection, who had continued to receive
      conventional rescue therapy. Two patients were unable to tolerate the treatments
      and were withdrawn from the study. Significant improvement in histologic
      rejection occurred in 14 of the remaining 16 patients after a mean of 37 days of
      aerosolized cyclosporine therapy. Measures of forced vital capacity and forced
      expiratory volume in 1 second (change in percent predicted/100 days plus or minus
      the standard error) increased over time in the treated patients whereas the
      condition of control patients declined despite repeated attempts at conventional
      rescue (forced vital capacity, aerosolized cyclosporine group, 4.6 +/- 2.9 vs
      control group -8.1 +/- 1.9, p = 0.001; forced expiratory volume in 1 second,
      aerosolized cyclosporine group, 2.1 +/- 4.4 vs control group -9.8 +/- 2.6, p =
      0.043). Renal and hepatic toxicity during cyclosporine therapy was not observed.
      The incidence of acute histologic rejection (> or = A2) decreased from 2.49 +/-
      0.68 episodes/100 days before aerosolized cyclosporine therapy to 0.72 +/- 0.3
      episodes/100 days (p < 0.05). In summary, aerosolized cyclosporine is a safe and
      effective therapy for acute rejection that has failed to improve with
      conventional treatment.

PMID- 9040629
TI  - Mitigation of injury in canine lung grafts by exogenous surfactant therapy.
AB  - BACKGROUND: Exogenous surfactant therapy of lung donors improves the preservation
      of normal canine grafts. The current study was designed to determine whether
      exogenous surfactant can mitigate the damage in lung grafts induced by mechanical
      ventilation before procurement. METHODS AND RESULTS: Five donor dogs were
      subjected to 8 hours of mechanical ventilation (tidal volume 45 ml/kg). This
      produced a significant decrease in oxygen tension (p = 0.007) and significant
      increases in bronchoscopic lavage fluid neutrophil count (p = 0.05), protein
      concentration (p = 0.002), and the ratio of poorly functioning small surfactant
      aggregates to superiorly functioning large aggregates (p = 0.02). Five other
      animals given instilled bovine lipid extract surfactant and undergoing mechanical
      ventilation in the same manner demonstrated no significant change in oxygen
      tension values, lavage fluid protein concentration, or the ratio of small to
      large aggregates. All 10 lung grafts were then stored for 17 hours at 4 degrees
      C. Left lungs were transplanted and reperfused for 6 hours. After 6 hours of
      reperfusion the ratio of oxygen tension to inspired oxygen fraction was 307 +/-
      63 mm Hg in lung grafts administered surfactant versus 73 +/- 14 mm Hg in
      untreated grafts (p = 0.007). Furthermore, peak inspired pressure was
      significantly (p < 0.05) lower in treated animals from 90 to 360 minutes of
      reperfusion. Analysis of lavage fluid of transplanted grafts after reperfusion
      revealed small to large aggregate ratios of 0.17 +/- 0.04 and 0.77 +/- 0.17 in
      treated versus untreated grafts, respectively (p = 0.009). CONCLUSIONS:
      Instillation of surfactant before mechanical ventilation reduced protein leak,
      maintained a low surfactant small to large aggregate ratio, and prevented a
      decrease of oxygen tension in donor animals. After transplantation, surfactant
      treated grafts had superior oxygen tension values and a higher proportion of
      superiorly functioning surfactant aggregate forms in the air space than untreated
      grafts. Exogenous surfactant therapy can protect lung grafts from ventilation
      induced injury and may offer a promising means to expand the donor pool.

PMID- 9040630
TI  - Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery
      bypass grafting.
AB  - OBJECTIVE: This prospective, randomized, clinical study was undertaken to
      determine whether glucose-insulin-potassium solutions would benefit patients
      undergoing coronary artery bypass grafting because of unstable angina. METHODS:
      The study group consisted of 30 patients with unstable angina who required
      coronary artery bypass grafting. In 15 patients, glucose-insulin-potassium
      solution (30% dextrose in water; K+, 80 mEq/L: regular insulin, 50 units) was
      given intravenously at 1 ml/kg per hour after induction of anesthesia and
      administration continued for 12 hours after aortic unclamping. Fifteen patients
      in a separate group received 5% dextrose in water intravenously at 50 ml/hr.
      RESULTS: Patients treated with glucose-insulin-potassium solution had higher
      cardiac indices (2.8 +/- 0.1 vs 2.0 +/- 1 L/min per square meter; p < 0.001),
      lower inotrope scores (0.06 +/- 0.01 vs 0.46 +/- 0.19; p = 0.041), and less
      weight gain (6.4 +/- 9 vs 11.6 +/- 1.1 pounds; p < 0.001) and had shorter times
      of ventilator support (8.3 +/- 0.6 vs 14.2 +/- 0.2 hours; p = 0.003). They had a
      significantly lower incidence of atrial fibrillation (13.3% vs 53.3%; p = 0.020)
      and had shorter stays in the intensive care unit (14.8 +/- 1.3 vs 31.6 +/- 5.2
      hours; p = 0.002) and in the hospital (6.0 +/- 0.4 vs 8.0 +/- 0.7 days; p =
      0.010). CONCLUSIONS: We conclude that glucose insulin-potassium therapy enhances
      myocardial performance and results in faster recovery from urgent coronary artery
      bypass grafting.

PMID- 9040631
TI  - Effective control of refractory pulmonary hypertension after cardiac operations.
AB  - OBJECTIVES: Inhaled nitric oxide is a promising therapy to control pulmonary
      hypertension. However, pulmonary hypertension caused by valvular heart disease is
      often refractory to inhaled nitric oxide. The objective of this study was to
      determine whether the combination of inhaled nitric oxide plus dipyridamole will
      cause a response in patients with pulmonary hypertension undergoing cardiac
      operations who had not responded to inhaled nitric oxide alone. METHODS:
      Responses in 10 patients (62 +/- 7 years) with pulmonary hypertension caused by
      aortic or mitral valvular disease (mean pulmonary artery pressure, > or = 30 mm
      Hg) were studied in the operating room after valve replacement. The effect of
      inhaled nitric oxide alone (40 ppm) on pulmonary vascular resistance, mean
      pulmonary artery pressure, cardiac output, and mean arterial pressure was
      determined. Inhaled nitric oxide administration was then stopped and patients
      were given dipyridamole (0.2 mg/kg intravenously); the effect of inhaled nitric
      oxide plus dipyridamole was then examined. RESULTS: Dipyridamole effected a
      response in patients who had not responded to nitric oxide. Pulmonary vascular
      resistance and mean pulmonary artery pressure were significantly reduced and
      cardiac output was increased without change in mean arterial pressure.
      CONCLUSIONS: Patients with refractory pulmonary hypertension in whom inhaled
      nitric oxide alone fails to cause a response may respond to combined therapy of
      inhaled nitric oxide plus dipyridamole. This therapy may be particularly valuable
      in patients with dysfunction of the right side of the heart as a result of
      pulmonary hypertension because of its effective lowering of right ventricular
      afterload.

PMID- 9040632
TI  - Correlation of functional recovery with myocardial blood flow, glucose uptake,
      and morphologic features in patients with chronic left ventricular ischemic
      dysfunction undergoing coronary artery bypass grafting.
AB  - OBJECTIVE: Our objective was to investigate the influence of preoperative
      myocardial ultrastructure and metabolism on recovery of contractile function
      after coronary artery bypass grafting in patients with coronary artery disease
      and left ventricular dysfunction. METHODS: Dynamic positron emission tomography
      with 13N-ammonia and 18F-deoxyglucose was used to assess myocardial perfusion and
      glucose uptake in 53 patients scheduled for coronary revascularization because of
      coronary artery disease and left ventricular dysfunction. The degree of tissue
      fibrosis and the presence of potentially reversible alterations of cardiomyocytes
      (loss of myofilaments and accumulation of glycogen) were quantified from
      transmural biopsy specimens. These were harvested from the center of the
      dysfunctional area during the operation and analyzed with a light microscope. The
      recovery of contractile performance was assessed from the changes in left
      ventricular function at contrast ventriculography or echocardiography before and
      6 months after the operation. RESULTS: According to postoperative changes in
      regional wall motion, left ventricular function was considered to have improved
      in 34 patients, whereas dysfunction persisted in 19 patients. In patients with
      improved wall motion, ejection fraction rose by 12% and end-systolic volume
      decreased by 28%. By contrast, in patients with persistent dysfunction, ejection
      fraction decreased by 6% and end-systolic volume increased by 25%. Before
      revascularization, myocardium with reversible dysfunction displayed higher levels
      of absolute myocardial blood flow, higher myocardial glucose uptake, less tissue
      fibrosis, and more altered cardiomyocytes than myocardium with persistent
      dysfunction. Significant correlations were found between regional blood flow and
      the surface of the biopsy specimen covered by fibrosis, as well as between
      glucose uptake and the density of altered cardiomyocytes. CONCLUSION: In patients
      with left ventricular ischemic dysfunction, the recovery of regional and global
      left ventricular function after surgical revascularization is associated with
      higher preoperative blood flow and glucose uptake, with less tissue fibrosis and
      a higher amount of viable cardiomyocytes in the dysfunctional area. The current
      study thus confirms the value of noninvasive preoperative metabolic imaging for
      identification of residual viable myocardium and for prediction of the functional
      outcome after revascularization.

PMID- 9040633
TI  - Endothelial stunning and myocyte recovery after reperfusion of jeopardized
      muscle: a role of L-arginine blood cardioplegia.
AB  - Ischemia and reperfusion may damage myocytes and endothelium in jeopardized
      hearts. This study tested whether (1) endothelial dysfunction (reduced nitric
      oxide release) exists despite good contractile performance and (2)
      supplementation of blood cardioplegic solution with nitric oxide precursor L
      arginine augments nitric oxide and restores endothelial function. Among 30
      Yorkshire-Duroc pigs, 6 received standard glutamate/aspartate blood cardioplegic
      solution without global ischemia. Twenty-four underwent 20 minutes of 37 degrees
      C global ischemia. Six received normal blood reperfusion. In 18, the aortic clamp
      remained in place 30 more minutes and all received 3 infusions of blood
      cardioplegic solution. In 6, the blood cardioplegic solution was unaltered; in 6,
      the blood cardioplegic solution contained L-arginine (a nitric oxide precursor)
      at 2 mmol/L; in 6, the blood cardioplegic solution contained the nitric oxide
      synthase inhibitor L-nitro arginine methyl ester (L-NAME) at 1 mmol/L. Complete
      contractile and endothelial recovery occurred without ischemia. In jeopardized
      hearts, complete systolic recovery followed infusion of blood cardioplegic
      solution and of blood cardioplegic solution plus L-arginine. Conversely,
      contractility recovered approximately 40% after infusion of normal blood and
      blood cardioplegic solution plus L-NAME. Postischemic nitric oxide production
      fell 50% in the groups that received blood cardioplegic solution and blood
      cardioplegic solution plus L-NAME but was increased in the group that received
      blood cardioplegic solution L-arginine. In vivo endothelium-dependent vasodilator
      responses to acetylcholine recovered 75% +/- 5% of baseline in the blood
      cardioplegic solution plus L-arginine group, but less than 20% of baseline in
      other jeopardized hearts. Endothelium-independent smooth muscle responses to
      sodium nitroprusside were relatively unaltered. Myeloperoxidase activity
      (neutrophil accumulation) was similar in the blood cardioplegic solution (without
      ischemia) and blood cardioplegic solution plus L-arginine groups (0.01 +/- 0.002
      vs 0.013 +/- 0.003 microgram/gm tissue). Myeloperoxidase activity was raised
      substantially to 0.033 +/- 0.002 microgram/gm after exposure to normal blood and
      to 0.025 +/- 0.003 microgram/gm after infusion of blood cardioplegic solution and
      was highest at 0.053 +/- 0.01 microgram/gm with exposure to blood cardioplegic
      solution plus L-NAME in jeopardized hearts. The discrepancy between contractile
      recovery and endothelial dysfunction in jeopardized muscle can be reversed by
      adding L-arginine to blood cardioplegic solution.

PMID- 9040634
TI  - Swine lungs expressing human complement-regulatory proteins are protected against
      acute pulmonary dysfunction in a human plasma perfusion model.
AB  - Pulmonary transplantation is currently limited by the number of suitable cadaver
      donor lungs. For this reason, pulmonary xenotransplantation is currently being
      investigated. OBJECTIVE: Our goal was to assess the role of complement in
      pulmonary xenograft dysfunction. METHODS: The pulmonary function of swine
      expressing human decay accelerating factor and human CD59 (n = 6) was compared
      with that of the lungs from nontransgenic (control) swine (n = 6) during
      perfusion with human plasma. RESULTS: After 2 hours of perfusion, the pulmonary
      vascular resistance was 1624 +/- 408 dynes.sec.cm-5 in control lungs and 908 +/-
      68 dynes.sec.cm-5 in transgenic lungs (p < 0.05). Control lungs had a venous
      oxygen tension of 271 +/- 23 mm Hg with a ratio of venous oxygen tension to
      inspired oxygen fraction of 452 +/- 38 at 2 hours of perfusion; transgenic lungs
      had a venous oxygen tension of 398 +/- 11 mm Hg and a ratio of venous oxygen
      tension to inspired oxygen fraction of 663 +/- 18 (p < 0.05). Control lungs
      showed a decrease of 79.8% +/- 3.7% in static pulmonary compliance by 2 hours,
      versus a 12.0% +/- 8.1% decrease by the transgenic lungs (p < 0.05). The control
      lungs also developed 561.7 +/- 196.2 ml of airway edema over 2 hours, in contrast
      to 6.5 +/- 1.7 ml in transgenic lungs (p < 0.05). CONCLUSION: Lungs from swine
      expressing human decay accelerating factor and human CD59 functioned better than
      nontransgenic swine lungs when perfused with human plasma. These results suggest
      that complement activation is involved in producing acute pulmonary xenograft
      dysfunction and demonstrate that lungs from swine expressing human decay
      accelerating factor and human CD59 are protected against pulmonary injury when
      perfused with human plasma.

PMID- 9040636
TI  - Successful repair of thoracic aortic aneurysm in a child with Ehlers-Danlos
      syndrome.

PMID- 9040635
TI  - Basal nitric oxide expresses endogenous cardioprotection during reperfusion by
      inhibition of neutrophil-mediated damage after surgical revascularization.
AB  - Ischemia-reperfusion damages endothelium and impairs basal production of nitric
      oxide. Basally released nitric oxide is cardioprotective by its inhibition of
      neutrophil activities. Loss of endogenous nitric oxide with endothelial injury
      may occur during two phases: cardioplegic ischemia and reperfusion (aortic
      declamping). This study tested the hypothesis that inhibition of endogenously
      released nitric oxide in hearts subjected to regional ischemia, cardioplegic
      arrest, and reperfusion (1) restricts endogenous cardioprotection and permits
      neutrophil-mediated damage and (2) expresses damage during the reperfusion phase.
      L-Nitro-arginine was used to block basal nitric oxide production. In 22
      anesthetized dogs, the left anterior descending artery was ligated for 90 minutes
      followed by 1 hour of arrest with cold multidose (every 20 minutes) blood
      cardioplegia. Dogs were divided into three groups: the first group received
      standard unsupplemented blood cardioplegia (group 1, n = 8), in the second group
      L-nitro-arginine was administered as an additive to blood cardioplegic solution
      (1 mmol) and as an infusion during reperfusion (34 mg/kg) (group 2, n = 7), and
      in the third group L-nitro-arginine was administered only at reperfusion (group
      3, n = 7). The ligature was released during the second infusion of cardioplegic
      solution. Infarct size (triphenyltetrazolium chloride) was increased in group 3
      (L-nitro-arginine only at reperfusion) compared with that in group 1 (standard
      blood cardioplegia) (49% +/- 6% vs 34% +/- 2%, respectively), but was not further
      extended in group 2 (L-nitro-arginine as an additive to blood cardioplegic
      solution and at reperfusion) (56% +/- 3%, p > 0.05 vs group 3), which suggests
      primarily a reperfusion process. Polymorphonuclear neutrophil-specific
      myeloperoxidase activity in the area at risk was elevated comparably in groups 2
      and 3 (group 2: 2.9 +/- 0.5 units/gm tissue, p = 0.06 vs group 1; group 3: 3.9 +/
      1.0 units/gm tissue, p < 0.05 vs group 1) compared with that in the standard
      blood cardioplegia group (1.7 +/- 0.3 units/gm tissue), suggesting
      polymorphonuclear neutrophil accumulation occurs primarily during reperfusion.
      Polymorphonuclear neutrophil adherence in ischemic-reperfused left anterior
      descending artery segments was comparably greater in group 2 (L-nitro-arginine as
      an additive to blood cardioplegic solution and at reperfusion: 195 +/- 21
      polymorphonuclear neutrophils/mm2 of artery, p < 0.05 vs group 1) and group 3 (L
      nitro-arginine only at reperfusion: 224 +/- 20 polymorphonuclear neutrophils/mm2
      of artery, p < 0.05 vs group 1) relative to that in group 1 (108 +/- 19
      polymorphonuclear neutrophils/mm2 of artery). There was no significant adherence
      to nonischemic circumflex arteries. We conclude that blockade of endogenous
      nitric oxide augments postischemic injury mediated by polymorphonuclear
      neutrophils, and this damage is expressed primarily during the reperfusion phase.

PMID- 9040637
TI  - Minimally invasive direct coronary artery bypass, percutaneous transluminal
      coronary angioplasty, and stent placement for left main stenosis.

PMID- 9040638
TI  - Video-assisted minimally invasive mitral valve surgery: the "micro-mitral"
      operation.

PMID- 9040639
TI  - Primary repair of rupture of a main and lobar bronchus.

PMID- 9040640
TI  - HLA antibodies specific for cryopreserved heart valve "homografts" in children.

PMID- 9040641
TI  - Multiple episodes of thrombosis with biventricular support devices with
      inadequate anticoagulation and evidence of accelerated intravascular coagulation.

PMID- 9040642
TI  - Cryopreserved homograft monocusp valves for reconstruction of the right
      ventricular outflow tract.

PMID- 9040643
TI  - Cost reduction by combined carotid endarterectomy and coronary bypass.

PMID- 9040644
TI  - Truncus arteriosus repair: influence of techniques of right ventricular outflow
      tract reconstruction.

PMID- 9040645
TI  - Controlled limb reperfusion in patients with severe limb ischemia.

PMID- 9040646
TI  - Failure of devices used for the closure of atrial septal defects.

PMID- 9040647
TI  - Purulent pericarditis.

PMID- 9040648
TI  - Safety of calcium-channel blockers.

PMID- 9040650
TI  - The current place of high-dose immunoglobulins in the treatment of neuromuscular
      disorders.
AB  - High-dose immunoglobulins for intravenous administration (IVIg) have originally
      been developed for substitution therapy in hypogammaglobulinemia. Over the last
      decade they are increasingly used in the treatment of immune-mediated diseases.
      In this review the results in immune-mediated neuromuscular diseases are
      summarized. Positive effects are demonstrated in open studies in dermato- and
      polymyositis, myasthenia gravis, and inflammatory neuropathies. Properly
      conducted randomized clinical trials demonstrating the effect of IVIg are
      available in dermatomyositis, Guillain-Barre syndrome, and chronic inflammatory
      demyelinating polyneuropathy, and smaller ones in multifocal motor neuropathy. In
      myasthenia gravis a trial is at present underway and only interim results are
      available. The results of a trial in the Lambert-Eaton myasthenic syndrome are in
      the process of publication. The therapeutic approach in individual patients is
      discussed, but often appears to be difficult. Considering chronic treatment with
      IVIg, proper long-term studies including cost-benefit studies are needed. Future
      developments aim for combination therapies, since IVIg and immune suppressants
      like prednisone are suggested to have a synergistic effect.

PMID- 9040649
TI  - More new drugs for HIV and associated infections.

PMID- 9040651
TI  - A special kind of anterior horn cell involvement in juvenile myoclonic epilepsy
      demonstrated by macro electromyography.
AB  - Juvenile myoclonic epilepsy (JME) is not an uncommon seizure disorder, occurring
      in 5-10% of epileptic patients. A subclinical anterior horn cell involvement has
      been suggested in some JME patients by concentric needle electromyography (EMG)
      and turn/amplitude analysis. In this study, 22 JME patients and 17 normal control
      subjects have been studied with macro EMG, which is a sensitive method to assess
      the size of motor units. Most JME patients (19 of 22) had a pathologically
      increased number of individual large macro motor unit action potentials (MUAPs)
      compared to control subjects. For both biceps brachii and tibialis anterior
      muscles, means of median macro MUAP amplitudes were significantly greater than
      those of normal controls, whereas the fiber density values were only slightly
      increased. This suggested another kind of anterior horn cell involvement in JME
      than seen in motor neuron diseases.

PMID- 9040652
TI  - Evaluation of carpal tunnel syndrome in patients with polyneuropathy.
AB  - The difference between the median nerve latency to the second lumbrical muscle
      and the ulnar nerve latency to the second interosseous muscle (L-I DIFF) was
      tested in a prospective study to discriminate whether prolonged distal motor
      latency of the median nerve in patients with polyneuropathy (PNP) reflects an
      additional carpal tunnel syndrome (CTS). We investigated 92 patients (107 hands)
      with CTS, 30 patients (34 hands) with PNP, 22 patients (27 hands) with CTS and
      coexisting PNP (PNP + CTS), and 77 controls (87 hands). L-I DIFF was
      significantly prolonged in both the CTS and PNP + CTS patients as compared to PNP
      patients and controls. It proved to be the most specific test to differentiate
      between diffuse (PNP) and focal (entrapment) nerve disorder.

PMID- 9040653
TI  - Macrophages and dendritic cells in normal and regenerating murine skeletal
      muscle.
AB  - Mononuclear phagocytes and MHC class II+ dendritic cells (DC) were identified in
      frozen sections of skeletal muscle using a panel of pan-specific antimacrophage
      (MOMA-2, SER-4, Mac-1, F4/80), anti-major histocompatibility complex (MHC) class
      II (M5/114) and anti-DC (NLDC-145, N418, M342) monoclonal antibodies. Uninjured
      and regenerating skeletal muscle were investigated in SJL/J and BALB/c mice,
      strains with known differences in muscle regenerative capacity. Resident tissue
      macrophages and MHC class II+ DC were present within uninjured mouse muscle. A
      subpopulation of DC were positive for the pan-DC markers, N418 and M342, and
      negative for the lymphoid DC marker NLDC-145. Following crush injury, the
      macrophage population increased by day 2, became marked by day 3, and had
      decreased by day 6. In contrast, the number of MHC class II+ cells around the
      injury site increased steadily after injury and remained high at day 6. The
      numbers of macrophages and DC detected by immunohistochemical staining were
      consistently higher in SJL/J than BALB/c muscles. This study confirms that
      macrophages are a significant component of normal murine skeletal muscle and that
      these cells increase dramatically after injury. Furthermore the data also reveal
      for the first time that DC are present in normal skeletal muscle and that MHC
      class II+ cells, including DC, increase after injury. The presence of DC in
      muscle has important implications for the understanding of the immunobiology of
      muscle and immune-mediated processes such as the host versus graft responses
      following muscle transplants and autoimmune diseases affecting this tissue.

PMID- 9040654
TI  - Loss of twitch torque following muscle compression.
AB  - With the elbow flexed, compression of the human biceps brachii has been found to
      reduce twitch torque, with an approximately linear relationship being observed
      between the loss of torque and the applied pressure (up to 45 kPa). The decline
      in torque could no longer be demonstrated when the biceps muscle was stretched,
      by extending the elbow from a flexed position. The loss of torque in the flexed
      position appeared to be due to an inability of muscle sarcomeres to bulge
      sufficiently to take up the series elasticity at the fiber ends.

PMID- 9040655
TI  - Functional effects of uridine triphosphate on the atrophied soleus muscle of rat
      after unloading.
AB  - The purposes of the study were to determine the effects of a pyrimidine
      nucleotide, the uridine triphosphate (UTP), on the contractile and histochemical
      properties of the soleus (SOL) muscle following disuse atrophy due to hindlimb
      unloading (HU) hypokinesia. UTP was injected either during the HU period (2
      weeks) or later during the recovery period. In this latter condition, contractile
      and histochemical properties were studied after 5, 8, 11, and 15 days of
      spontaneous recovery. HU induced decreases in the SOL weight, force output
      (twitch and tetanic tensions), time to peak tension during the twitch, and the
      percentage of type I fibers. The injection of UTP during the HU period did not
      counteract the modification in speed-related properties, but the decrease in
      force output was partly counteracted and the proportion of type II C fibers was
      increased. When UTP was injected during the recovery periods, force-related
      properties recovered more rapidly. These results suggest that UTP may reduce the
      loss of force induced by atrophy.

PMID- 9040656
TI  - A longitudinal study comparing thenar motor unit number estimates to other
      quantitative tests in patients with amyotrophic lateral sclerosis.
AB  - The following data were obtained on 21 amyotrophic lateral sclerosis (ALS)
      patients, aged 36-76 years (mean: 58 years), at baseline and months 4, 8, and 12:
      thenar motor unit number estimate (MUNE) using multiple point stimulation, mean
      thenar surface-recorded motor unit action potential negative-peak area, thenar
      compound muscle action potential amplitude, isometric hand grip strength, total
      Medical Research Council (MRC) manual muscle testing score, Appel ALS rating
      scale, and forced vital capacity (FVC). The absolute mean rate of change per
      month was significantly greater (P < 0.01) for MUNE values than for MRC and FVC
      values in the 21 ALS patients. In a subset of patients (n = 6) with slowly
      progressive disease, the absolute mean rate of change per month was significantly
      greater (P < 0.01) for MUNE values than for all other test values. In addition,
      MUNE values were the most sensitive index for documenting changes in disease
      progression over time.

PMID- 9040657
TI  - Expression of nerve-regulated genes in muscles of mouse mutants affected by
      spinal muscular atrophies and muscular dystrophies.
AB  - The expression of the genes for the alpha-subunit of AChR (AChR alpha), for the
      myogenic factors myogenin and MyoD, for the calcium-binding protein parvalbumin
      (PV), and for the muscular chloride channel CIC-1 was studied in the three mouse
      spinal muscular atrophies (SMAs). These were the mutants "wobbler" (WR), "muscle
      deficient" (MDF) and "progressive motor neuronopathy" (PMN). Murine myopathies
      "muscular dystrophy with myositis" (MDM) and "X-linked muscular dystrophy" (MDX)
      were used as controls. AChR alpha and myogenin mRNA levels were strongly elevated
      in muscles affected by SMAs (reflecting denervation), whereas only myogenin mRNA
      was moderately elevated in MDX and MDM muscles, probably due to fiber
      regeneration. As in denervated muscle, CIC-1 and PV mRNA levels were lowered in
      SMAs. No changes were seen in muscles of up to 222-day-old symptomless ciliary
      neurotrophic factor (CNTF) knockout mice. The patterns of gene expression were
      characteristic for the type of muscle disease, indicating their possible
      usefulness for clinical diagnosis.

PMID- 9040658
TI  - Temperature-sensitive repetitive discharges in paramyotonia congenita.
AB  - A 47-year-old female with paramyotonia congenita was studied with
      electromyography and showed minimal myotonic discharges but prominent repetitive
      discharges in hand muscles at room temperature. With cooling the hand, the
      repetitive discharges ceased as the myotonic potentials became prominent. With
      exercise and further cooling, the myotonic discharges increased and the strength
      of the muscle and recruitment pattern decreased. With warming, the myotonic
      discharges decreased as the repetitive discharges reappeared. This is the first
      report of repetitive discharges occurring in a patient with temperature-sensitive
      sodium channel myotonia. It is postulated that the repetitive discharges as well
      as the myotonic discharges are the manifestation of muscle membrane
      hyperexcitability secondary to the abnormal, noninactivating sodium channels.

PMID- 9040659
TI  - Quantitative sensory testing.
AB  - Quantitative sensory testing has become commonplace in clinical neurophysiology
      units. Measurement of the thermal and vibratory senses provides an estimate on
      function of sensory small and large fibers, respectively. Being psychophysical
      parameters, sensory threshold values are not objective, and various test
      algorithms have been developed aiming at optimized results. In this review the
      various test algorithms are screened, and their relative advantages and
      disadvantages are discussed. Considerations of quality control are reviewed, and
      the main fields of clinical application are described.

PMID- 9040660
TI  - Clinical and prognostic features in unilateral femoral neuropathies.
AB  - We have examined the clinical features of patients with femoral neuropathy and
      the factors that influence the prognosis. Of 80 consecutive patients referred for
      neurophysiological evaluations of proximal lower limb weakness, 32 fulfilled
      strict inclusion criteria and had adequate information, including estimates of
      axon loss (AxL) by stimulation of the bilateral femoral nerve. In 31, the Kaplan
      Meier method was used to describe the time course of the outcome, while logistic
      regression was employed to determine the contributing factors. Excellent,
      satisfactory, and poor outcomes were seen in 10 (31%), 11 (34%), and 10 (31%)
      patients, respectively. Logistic regression analysis of seven factors
      demonstrated that the estimate of AxL was the only significant variable. The best
      prognostic factor was an estimate of AxL < or = 50%, with all patients fulfilling
      this criterion showing improvement with 1 year; fewer than half the patients with
      AxL > 50% should be expected to improve. This study clearly shows that,
      irrespective of the cause of femoral neuropathy, functional improvement is seen
      in 2 out of 3 patients within 2 years and that the estimate of AxL is the only
      factor influencing prognosis.

PMID- 9040661
TI  - Motor unit forces and recruitment patterns after cervical spinal cord injury.
AB  - Force was measured from triceps brachii motor units in individuals with chronic
      cervical spinal cord injury (SCI) and in able-bodied (A-B) control subjects using
      spike-triggered averaging (175 and 48 units, respectively). Eleven percent of
      units from the SCI population generated normal electromyograms (EMGs) but exerted
      no measurable force, 65% generated force comparable to the control data, while
      24% were stronger than usual. Weak units probably reflect disuse. Muscle
      shortening, densely innervated territories, and polyphasic EMG potentials
      suggested strong units resulted from intact axons sprouting to reinnervate
      denervated muscle. Many units from SCI subjects had faster than normal
      contraction times (CTs). The force and CT distributions from the SCI and A-B
      populations differed significantly. Motor units of SCI subjects were recruited in
      order of increasing force output and increasing contraction time. Chronic
      cervical SCI therefore seems to alter the expected triceps brachii motor unit
      force-speed relations.

PMID- 9040663
TI  - Motor evoked potentials in the spinocerebellar ataxias type 1 and type 3.

PMID- 9040662
TI  - Maternally inherited cardiomyopathy: a new phenotype associated with the A to G
      AT nt.3243 of mitochondrial DNA (MELAS mutation).
AB  - The A to G transition at nt.3243 of the tRNALeu(UUR) gene of mtDNA, commonly
      associated with MELAS, was detected in several members of a family affected by a
      maternally inherited form of hypertrophic cardiomyopathy. These findings suggest
      adding cardiomyopathy in the list of phenotypes associated with the 3243
      mutation.

PMID- 9040664
TI  - Painful neuropathy after diffuse herpes zoster.

PMID- 9040665
TI  - Effects of CTG trinucleotide repeat expansion in leukocytes on quantitative
      muscle histopathology in myotonic dystrophy.

PMID- 9040666
TI  - The exercise test distinguishes proximal myotonic myopathy from myotonic
      dystrophy.

PMID- 9040667
TI  - Lipoamide dehydrogenase deficiency: a new cause for recurrent myoglobinuria.

PMID- 9040668
TI  - Root mean square voltage/turns in chronic neuropathies is related to increase in
      fiber density.

PMID- 9040669
TI  - Treatment of idiopathic lumbosacral plexopathy with intravenous immunoglobulin.

PMID- 9040671
TI  - Multi-motor unit action potential analysis (MMA)

PMID- 9040670
TI  - Electromyographic changes in vastus lateralis during dynamic exercise.

PMID- 9040672
TI  - Acoustic myography.

PMID- 9040673
TI  - Case report: acute vaccine-associated paralytic poliomyelitis.

PMID- 9040675
TI  - Incidence of stroke and myocardial infarction in women of reproductive age.
AB  - BACKGROUND AND PURPOSE: Information on the incidence of vascular disease in women
      of reproductive age has been limited. These disease are rare in this age group,
      and a large population base is required for reliable estimation of incidence.
      METHODS: For a case-control study of vascular disease and low-dose oral
      contraceptive use, we used emergency department logs and hospital admission and
      discharge records to ascertain fatal and nonfatal cases of first-ever stroke and
      myocardial infarction (MI) in women 15 to 44 years of age who were-members of a
      large California HMO. Incidence rates of stroke and MI were calculated on the
      basis of these data. RESULTS: The incidence of MI not associated with pregnancy
      was 5.0 per 100,000 women-years. The incidence of stroke not associated with
      pregnancy was 10.7 per 100,000 women-years. MI was very rare until age 35 years.
      At every age, about half of hemorrhagic strokes were due to subarachnoid
      hemorrhage. CONCLUSIONS: The incidence rates of stroke and MI are low in women of
      reproductive age in the United States.

PMID- 9040674
TI  - Stroke rates during the 1980s. The Minnesota Stroke Survey.
AB  - BACKGROUND AND PURPOSE: The decline in stroke mortality it the United States may
      have resulted from declining incidence improved survival of stroke patients, or
      both. We previously reported that stroke patients who were 30 to 74 years old and
      were treated in Minneapolis/St Paul hospitals in 1990 survived longer than did
      their counterparts in 1980. In the present study, we examined trends in the rate
      of hospitalized stroke in Minneapolis/ St Paul between 1980 and 1990. METHODS:
      For 1980, 1985, and 1990, we obtained lists of discharge codes (International
      Classification of Diseases, 9th revision) from Minneapolis/St Paul hospitals,
      identified hospitalizations for acute cerebrovascular disease, and randomly
      selected 50% of the cases for medical record abstraction. We counted stroke
      events in five different ways, which were based on discharge codes as well as
      diagnostic criteria, and computed age adjusted stroke rates for each year. Stroke
      mortality in the population was computed for 1960 through 1994. RESULTS: Among
      men, all five measures of hospitalized stroke attack rate indicated a decline
      between 1980 and 1985, which ranged from 5% to > 20%. Among women, there was a
      sharp contrast between trends that relied on discharge codes and trends that
      relied on diagnostic criteria: the former indicated a decline (4% to 19%),
      whereas the latter indicated some increase. For the second half of the 1980s,
      most measures of stroke attack rate in men, all measures of stroke attack rate in
      women, and measures of stroke incidence in both sexes did not indicate a decline
      in stroke occurrence in the population. Mortality from stroke among 30- to 74
      year-old residents of Minneapolis/St Paul, which declined rapidly during the
      1970s and early 1980s, declined slowly, if at all, during the second half of the
      1980s and early 1990s. CONCLUSIONS: The incidence of stroke may have declined
      among 30- to 74-year-old residents of Minneapolis/St Paul in the early 1980s.
      However, we found little indication of such a trend between 1985 and 1990, a
      period of slow decline or no decline in stroke mortality in that population.

PMID- 9040676
TI  - Stroke in a defined elderly population, 1967-1985. A less lethal and disabling
      but no less common disease.
AB  - BACKGROUND AND PURPOSE: Decline in stroke mortality in recent decades has been
      well documented in the United States and other countries. This study, based on a
      well-defined population with comprehensive medical records available for research
      purposes, seeks to explain decline in stroke mortality among older persons
      between 1967 and 1985. The study specifically explores the competing explanatory
      mechanisms of decreased incidence of stroke versus decreased case-fatality rate.
      METHODS: We conducted a retrospective analysis of three successive period cohorts
      (1967 through 1971, 1974 through 1978, and 1981 through 1985) of persons > or =
      65 years of age enrolled in a large group model HMO in a metropolitan community.
      All new hospitalized and a sample of nonhospitalized strokes were ascertained,
      and samples of first-ever strokes were studied. Incidence, case-fatality rates,
      survival times, and comorbidities were compared across cohorts. RESULTS: There
      was no significant change in stroke incidence over time; however, 1-month case
      fatality declined dramatically from 33% in 1967 through 1971 to 18% in 1981
      through 1985 (P < .01); median survival increased from 213 to 1092 days. Indices
      of reduced severity included declines in coma from 27% to 12% (P < .01) and in
      wheelchair- or bed-bound status from 40% to 30% (P = .067). Cases with and
      without CT scan in 1981 to 1985, when this procedure became widely available in
      the health plan, were similar in severity, thereby reducing the possibility of
      ascertainment bias. CONCLUSIONS: In this well-defined older population, stroke
      has become a less lethal and disabling though no less common disease. This
      finding fails to support the "compression of morbidity" hypothesis while
      supporting a model of delayed progression for stroke in this age group.

PMID- 9040677
TI  - Asymptomatic carotid endarterectomy. Patient and surgeon selection.
AB  - BACKGROUND AND PURPOSE: The applicability of prospective carotid endarterectomy
      protocols to the general population has been questioned. Outcomes for
      asymptomatic patients undergoing carotid endarterectomy were compared with the
      results of the Asymptomatic Carotid Atherosclerosis Study (ACAS) patients treated
      concurrently at our institution. METHODS: Asymptomatic patients undergoing
      carotid endarterectomies (n = 277) from 1987 to 1993 (ACAS enrollment period)
      were reviewed. Primary end points were mortality, myocardial infarction, and
      stroke. Five subgroups were studied: (1) ACAS surgical patients; (2) ACAS
      eligible patients not enrolled and ACAS surgeons; (3) ACAS-eligible patients not
      enrolled and non-ACAS surgeons; (4) ACAS-ineligible patients and ACAS surgeons;
      and (5) ACAS-ineligible patients and non-ACAS surgeons. RESULTS: ACAS-eligible
      patients were younger (P = .014), had more severe carotid stenosis (P = .001),
      and had lower incidences of pulmonary (P = .015) and renal (P = .008) diseases
      compared with ineligible patients. Patient selection (ACAS eligibility)
      significantly improved outcomes for mortality (P = .014) and myocardial
      infarction (P = .006). Length of stay favored ACAS-eligible patients (P = .004).
      ACAS surgeons operated on more severely stenotic carotid lesions (P = .005) and
      on patients with a lower incidence of coronary artery disease (P = .007). There
      was no difference in outcomes between ACAS and non-ACAS surgeons. CONCLUSIONS:
      Patient selection was a significant factor in determining outcome. With strict
      adherence to ACAS enrollment guidelines, the conclusions of ACAS appear
      applicable to patients seen at our institution with asymptomatic carotid
      stenosis.

PMID- 9040678
TI  - Risk factors for falls of hospitalized stroke patients.
AB  - BACKGROUND AND PURPOSE: Patients with stroke are at a high risk for falling. We
      assessed the fall incidence and risk factors for patients hospitalized as the
      result of an acute stroke. METHODS: We studied a cohort of 720 stroke patients
      from 23 hospitals in The Netherlands. The data were abstracted from the medical
      and nursing records. RESULTS: We studied 346 women and 374 men with a median age
      of 75 years; 77% of the patients had had a cerebral infarct, 17% had had a
      hemorrhage, and 6% had had an undefined stroke. We recorded 104 patients (14%)
      who fell at least once; there were a total of 173 falls. The incidence of falls
      was 8.9/1000 patients per day. The daily incidence was 6.2/1000 patients for
      first falls and 17.9/1000 patients for second falls. Heart disease (relative risk
      [RR], 1.6; 95% confidence interval [CI], 1.0 to 2.4), mental decline (RR, 1.6;
      95% CI, 1.0 to 2.4), and urinary incontinence (RR, 2.3; 95% CI, 1.3 to 4.1) were
      incremental risk factors for first falls, whereas the use of major psychotropic
      drugs lowered the fall risk (RR, 0.5; 95% CI, 0.3 to 0.8). The fall RR for
      patients with one previous fall was 2.2 (95% CI, 1.5 to 3.2), adjusted for the
      other risk factors. Most falls occurred during the day. Approximately 25% of the
      falls caused slight-to-severe injury, whereas three falls (2%) led to hip
      fractures. CONCLUSIONS: Stroke patients have at risk of falling. The
      identification of patients at risk may be a first step toward the implementation
      of fall-prevention measures for these patients.

PMID- 9040679
TI  - Reliability of hemorrhagic transformation diagnosis in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Diagnosis of hemorrhagic transformation (HT) could
      influence the prognosis and the management of acute ischemic stroke. The
      interobserver reliability of CT-scan HT classification is evaluated in the
      present study. METHODS: Fifty 5-day CT scans of patients enrolled in the
      Multicenter Acute Stroke Trial-Italy (MAST-I) were reviewed independently by two
      neuroradiologists and one neurologist with CT training. They evaluated the
      presence and type of intraparenchymal HT (hemorrhagic infarction types I, II, and
      III and intracerebral hemorrhage) (five-item scale), as well as the presence of
      intraventricular and/or subarachnoid bleeding according to standardized
      definitions. RESULTS: Agreement for exclusion of HT and intraventricular/
      subarachnoid bleeding was good between the neuroradiologists (kappa = 0.70 and
      kappa = 0.72) and excellent between the neurologist and each neuroradiologist
      (kappa = 0.87 and kappa = 0.77, kappa = 0.83, and kappa = 0.81, respectively).
      The overall agreement for the five-item HT scale between the two
      neuroradiologists was good (kappa n = 0.65) because of discordance over the last
      three items. Better overall agreement was obtained with a three-item scale: no
      hemorrhage, petechial type I hemorrhagic infarction, and other HT (type II and
      type III hemorrhagic infarction and intracerebral hemorrhage) together (kappa w =
      0.82 CONCLUSIONS: Exclusion of HT is a reliable CT diagnosis when made by
      neuroradiologists and also by a neurologist with CT training. Five- and three
      item scales of HT types showed good to excellent reliability. The validity of the
      scale for predicting short- and long-term outcome should be evaluated in future
      studies.

PMID- 9040680
TI  - Reliability of the National Institutes of Health Stroke Scale. Extension to non
      neurologists in the context of a clinical trial.
AB  - BACKGROUND AND PURPOSE: The reliability of the National Institutes of Health
      Stroke Scale (NIHSS) has been established through testing its use in live and
      videotaped patients. This reliability testing has primarily focused on the use of
      the scale by neurologists. We sought to determine the reliability of the NIHSS as
      used by non-neurologists in the context of a clinical trial. METHODS: In
      anticipation of the initiation of a randomized trial of a new therapy for
      patients with acute ischemic stroke, 30 physician investigators (30% of whom were
      not neurologists) and 29 non-physician study coordinators were trained in the use
      of the NIHSS at an informational and training conference using standardized
      videotaped patient examinations. A series of 4 patients were rated initially.
      After 3 months, the same 4 patients were rerated, providing a measure of
      intraobserver reliability. An additional series of 4 new patients were also rated
      after 3 months and, with the initial 4 ratings, provided data for assessment of
      interobserver reliability. RESULTS: Overall, 28% of the raters had previous
      experience with the NIHSS, and 22% had previously used the videotapes as used in
      the present trial. The coefficients of determination (r2) were each greater than
      .95 when the means of the two ratings of the same 4 cases were compared between
      (1) neurologists and other types of physicians, (2) physicians and study
      coordinators, (3) raters who had prior experience with the NIHSS and those
      without prior experience, and (4) raters who had used the videotapes in the past
      and those who had never viewed the tapes. The calculated r2s were greater than
      .98 for the initial rating of the first 4 cases and for the later rating of the 4
      new cases. The slopes of the regression lines were all near 1, indicating that
      the raters were similarly calibrated. The intraclass correlation coefficients
      were .93 and .95, reflecting high levels of intraobserver and interobserver
      reliability. CONCLUSIONS: These data extend the previously demonstrated
      reliability of the NIHSS to non-neurologists and show that both a variety of
      physician investigators and nurse study coordinators can be rapidly trained to
      reliably apply the scale in the context of an actual clinical trial.

PMID- 9040681
TI  - Atrial fibrillation and stroke. Mortality and causes of death after the first
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is a risk factor for stroke.
      This study was undertaken to determine the influence of AF on the mortality of
      stroke patients and on the causes of death after a stroke event. METHODS:
      Patients with first ischemic stroke who were .35 to 74 years old and registered
      in the FINMONICA stroke register during 1982 through 1992 were analyzed (n =
      6912). There were 642 patients with AF (9.3%) (mean age, 67 years) and 6270
      patients without AF (90.3%) (mean age, 63 years). The association between AF and
      stroke mortality was investigated by use of logistic regression and Cox
      proportional hazards models. RESULTS: Mortality was higher in the AF group both
      at 28 days (19.5% versus 14.4%, P < .001) and 1 year after the attack (30.5%
      versus 21.8%, P < .001). After adjustment for age and sex, the odds ratio for 28
      day case fatality (AF versus non-AF) was 1.27 (95% CI, 1.03 to 1.56; P = .003),
      and that for 1-year mortality was 1.36 (95% CI, 1.14 to 1.63; P < .001). In the
      proportional hazards model, AF was a significant independent risk factor for 1
      year mortality (hazard ratio, 1.26; 95% CI, 1.09 to 1.46; P = .002). Cardiac
      causes of death were more common in the AF group at the acute stage. In the
      course of 1 year, there were no differences in the distributions of causes of
      death. CONCLUSIONS: Stroke patients with AF are at high risk of death both at the
      acute phase of stroke and during the subsequent year after the first acute stroke
      event. Mortality from cardiac diseases prevailed in the AF group during the acute
      phase of stroke. Careful cardiac evaluation and treatment are essential in
      patients with AF and stroke.

PMID- 9040682
TI  - Atrial fibrillation and dementia in a population-based study. The Rotterdam
      Study.
AB  - BACKGROUND AND PURPOSE: Atrial fibrillation is a frequent disorder in the elderly
      and a known risk factor for cerebrovascular stroke. We investigated the
      association of atrial fibrillation with dementia and cognitive impairment in a
      large cross-sectional, population-based study in the elderly. METHODS: Of the
      6584 participants in the Rotterdam Study aged 55 to 106 years, detailed
      information on dementia status and ECG abnormalities was available. Dementia was
      diagnosed in three phases. First, participants were screened. Screen-positive
      subjects were tested further. Those with possible dementia underwent an extensive
      diagnostic workup. Dementia and dementia subtypes were diagnosed according to
      prevailing criteria. Cognitive impairment was defined as a Mini-Mental State
      Examination test score of < 26 points for a nondemented subject. RESULTS: Atrial
      fibrillation was diagnosed in 195, dementia in 276, and cognitive impairment in
      635 subjects. We found significant positive associations of atrial fibrillation
      with both dementia and impaired cognitive function (age- and sex-adjusted odds
      ratios, 2.3 [95% confidence interval, 1.4 to 3.7] and 1.7 [95% confidence
      interval, 1.2 to 2.5]), respectively). The strongest association was found not
      for vascular dementia but rather for Alzheimer's disease with cerebrovascular
      disease. The associations were stronger in women, and the relation with dementia
      was more pronounced in the relatively younger elderly. A history of stroke in
      subjects with atrial fibrillation could not account for these associations.
      CONCLUSIONS: Dementia and subtypes Alzheimer's disease and vascular dementia may
      be related to atrial fibrillation even if no clinical stokes have occurred.

PMID- 9040683
TI  - Clinically silent microemboli in patients with artificial prosthetic aortic
      valves are predominantly gaseous and not solid.
AB  - BACKGROUND AND PURPOSE: Microembolic signals (MES) are frequently observed by
      transcranial Doppler ultrasound after prosthetic heart valve implantation.
      Whether these MES are due to solid or gaseous particles is uncertain. We
      hypothesized that MES are gaseous and that if they are due to cavitation effects,
      their occurrence should respond to changes of dissolved oxygen concentration in
      the blood. METHODS: Transcranial monitoring of MES was performed in five patients
      with prosthetic aortic valves, who inspired 100% oxygen through a facial mask. In
      one patient 100% oxygen was administered under hyperbaric (2.5 kPa) conditions in
      a hyperbaric chamber. RESULTS: Inspiration of 100% oxygen reduced the total
      number of MES from 96/30 min to 2/30 min. Increasing the concentration of
      dissolved oxygen in the hyperbaric chamber led to an increase from 0.3 MES per
      minute (1.0 kPa) to 0.9 MES per minute (2.5 kPa). CONCLUSIONS: The dependence of
      occurrence of MES in patients with prosthetic cardiac valves on the oxygen
      partial pressure in blood provides strong evidence that these microemboli are
      gaseous.

PMID- 9040684
TI  - Treadmill aerobic exercise training reduces the energy expenditure and
      cardiovascular demands of hemiparetic gait in chronic stroke patients. A
      preliminary report.
AB  - BACKGROUND AND PURPOSE: Elevated energy costs of hemiparetic gait contribute to
      functional disability after stroke, particularly in physically deconditioned
      older patients. We investigated the effects of 6 months of treadmill aerobic
      exercise training on the energy expenditure and cardiovascular demands of
      submaximal effort ambulation in stroke patients with chronic hemiparetic gait.
      METHODS: Nine older stroke patients with chronic hemiparetic gait were enrolled
      in a 6-month program of low-intensity aerobic exercise using a graded treadmill.
      Repeated measures of energy expenditure based on steady state oxygen consumption
      during a standardized 1-mph submaximal effort treadmill walking task were
      performed before and after training. RESULTS: Six months of exercise training
      produced significant reductions in energy expenditure (n = 9; 3.40 +/- 0.27
      versus 2.72 +/- 0.25 kcal/min [mean +/- SEM]; P < .005) during a given submaximal
      effort treadmill walking task. Repeated measures analysis in the subset of
      patients (n = 8) tested at baseline and after 3 and 6 months revealed that
      reductions in energy expenditure were progressive (F = 11.1; P < .02) and that
      exercise-mediated declines in both oxygen consumption (F = 9.7; P < .02) and
      respiratory exchange ratio (F = 13.4; P < .01) occurred in a strong linear
      pattern. These stroke patients could perform the same standardized submaximal
      exercise task at progressively lower heart rates after 3 months (96 +/- 4 versus
      87 +/- 4 beats per minute) and 6 months of training (82 +/- 4 beats per minute; F
      = 35.4; P < .002). CONCLUSIONS: Six months of low-intensity treadmill endurance
      training produces substantial and progressive reductions in the energy
      expenditure and cardiovascular demands of walking in older patients with chronic
      hemiparetic stroke. This suggests that task-oriented aerobic exercise may improve
      functional mobility and the cardiovascular fitness profile in this population.

PMID- 9040685
TI  - Clinical evaluation of near-infrared spectroscopy for testing cerebrovascular
      reactivity in patients with carotid artery disease.
AB  - BACKGROUND AND PURPOSE: Near-infrared spectroscopy (NIRS) derives information
      about the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) from
      measurements of light attenuation caused by these chromosphores. The aim of this
      study was to assess NIRS as a tool for testing CO2 reactivity in patients with
      carotid artery disease. METHODS: One hundred patients with symptomatic carotid
      occlusive disease were examined (age range, 44 to 83 years). The severity of
      stenosis ranged from 30% to 100% (median, 80%) on the ipsilateral side and 0% to
      100% (median, 30%) on the contralateral side. Monitored parameters included
      transcranial Doppler flow velocity, changes in concentration of HbO2 and Hb,
      cutaneous laser-Doppler blood flow, endtidal CO2, arterial blood pressure, and
      arterial oxygen saturation. Hypercapnia was induced with the use of a 5% CO2/air
      mixture for inhalation. To estimate the contribution of skin flow to NIRS during
      reactivity testing, the superficial temporal artery was compressed, and the NIRS
      changes in response to the fall in laser-Doppler blood flow were recorded.
      Finally, reproducibility of reactivity testing was assessed in 10 patients who
      were subjected to repeated examinations over 3 days. RESULTS: Flow velocity- and
      HbO2-derived reactivity values were related to the severity of the stenosis (P =
      .0001 and P = .017, respectively). The correlation between the two reactivity
      modalities was significant (r = .49, P < .000001). The median estimated
      contribution of skin flow to NIRS changes was 15.8%. Another variable affecting
      HbO2 signal changes during the CO2 challenge was arterial blood pressure (P =
      .025). Reproducibility of HbO2 reactivity was similar to flow velocity reactivity
      (14.3% and 18.6% variation, respectively). CONCLUSIONS: NIRS shows potential as
      an alternative technique for testing CO2 reactivity in patients with carotid
      disease provided that conditions are carefully controlled. Marked changes in
      arterial blood pressure may render the NIRS reactivity indices unreliable, and
      the contribution from extracranial tissue must be taken into account when
      significant.

PMID- 9040686
TI  - Correlation of peak systolic velocity and angiographic measurement of carotid
      stenosis revisited.
AB  - BACKGROUND AND PURPOSE: Recent observations from the North American Symptomatic
      Carotid Endarterectomy Trial (NASCET) questioned the reliability of peak systolic
      velocity (PSV) criteria for grading carotid stenosis. We compared PSV and
      angiographic measurements at our center together with known physiological
      relationships to investigate the accuracy of ultrasound. METHODS: Consecutive
      patients who underwent both color-coded duplex ultrasound and intra-arterial
      digital subtraction angiography were studied. PSV was determined with angle
      correction at the site of the tightest internal carotid artery narrowing. Carotid
      stenosis was measured on angiograms with the North American (N) and common
      carotid (C) methods. Variables for the stepwise multiple linear regression
      analysis were selected from an axisymmetrical flow model. RESULTS: Eighty
      bifurcations were imaged in 40 patients. PSV did not exceed 140 cm/s in normal
      vessels. In diseased arteries, PSV increased proportionally with increasing
      stenosis and decreased to 0 cm/s at occlusion. In stepwise selection of
      polynomial terms, the linear, quadratic, and cubic correlations of .38, .17, and
      .22 for N and .45, .24, and .03 for C were found to be significant (P < .02).
      When only stenosed vessels were evaluated, PSV increase was found with greater
      scatter for the N measurement: r2 = .73 for N and r2 = .85 for C (n = 50; P = .03
      for the difference between two correlated correlation coefficients). CONCLUSIONS:
      At our laboratory PSV consistently correlates well with N and C angiographic
      measurements, as determined with a simple flow model. The complex nature of these
      correlations and greater variability of the N measurement should be taken into
      account when data from different centers are compared.

PMID- 9040687
TI  - Consistency of Doppler parameters in predicting arteriographically confirmed
      carotid stenosis. Asymptomatic Carotid Atherosclerosis Study Investigators.
AB  - BACKGROUND AND PURPOSE: While internal carotid peak systolic velocity (IPSV) is
      reportedly the best Doppler parameter for predicting lower grades of carotid
      artery stenosis, the internal carotid end-diastolic velocity (IEDV) or the ratio
      of IPSV to common carotid end-diastolic velocity (CEDV) is helpful in increasing
      prediction of higher grade stenoses. It is important to examine the consistency
      of these findings across machine and technician. METHODS: Using data from 10
      devices from the Asymptomatic Carotid Atherosclerosis Study, we examined the
      predictive ability of seven Doppler parameters: IPSV, IEDV, CEDV, common carotid
      peak systolic velocity (CPSV), and the ratios of IPSV/ CEDV, IEDV/CEDV, and
      IEDV/CEDV. To assess the agreement between Doppler and arteriography in
      classifying percent stenosis above or below a given criterion, sensitivity,
      specificity, area under the receiver operating curve, and kappa statistics were
      obtained from logistic models. The single best Doppler parameter for each of two
      grades of stenosis (60% and 80%) was determined, and its predictive ability was
      compared with that of IPSV. The usefulness of IEDV or IPSV/CEDV in addition to
      IPSV to determine higher grade stenosis was examined. RESULTS: IPSV was the best
      predictor in 9 of 10 devices at 60% and in 4 devices at 80% stenosis. When
      another parameter was better than IPSV, the improvement was minimal. Including
      IEDV or IPSV/CEDV in addition to IPSV did not notably improve predictive ability.
      CONCLUSIONS: IPSV is the single best Doppler parameter for distinguishing severe
      (> 80%) from less severe carotid stenosis. Information from other Doppler
      parameters in addition to IPSV is unlikely to be helpful.

PMID- 9040688
TI  - Relationship between carotid intima-media thickness and symptomatic and
      asymptomatic peripheral arterial disease. The Edinburgh Artery Study.
AB  - BACKGROUND AND PURPOSE: Ultrasonic evaluation of intimamedia thickness (IMT) is
      one method of assessing the development of early atherosclerosis. This report
      describes the distribution of IMT within the general population and is one of the
      first to investigate its association with noninvasively assessed symptomatic and
      asymptomatic peripheral arterial disease. METHODS: Ultrasonic evaluation of IMT
      was included in the 5-year follow-up examination of participants of the Edinburgh
      Artery Study. Valid readings of IMT were recorded in 1106 subjects aged 60 to 80
      years, and the maximum from the right and left sides of the neck was used in the
      analysis. Existing symptomatic and asymptomatic peripheral arterial disease and
      coronary heart disease were also assessed at follow-up using previously validated
      noninvasive techniques. RESULTS: IMT increased continuously with age (P < or =
      .01), and its distribution was positively skewed in both sexes. The results
      suggest that levels of atherosclerotic development in the common carotid artery
      are 5 to 10 years more advanced in men than in women. In this population, the
      overall prevalence of moderate to severe disease was very low (only 1.2% of study
      participants had IMT values > 2 mm). The presence of symptomatic (intermittent
      claudication) or asymptomatic (ankle brachial pressure index < or = 0.9)
      peripheral arterial disease was significantly associated with increased IMT (P <
      or = .05). CONCLUSIONS: Although the prevalence of advanced atherosclerosis was
      very low, small changes in IMT were associated with clinically significant
      development of atherosclerosis in the peripheral arteries. However, further
      longitudinal studies are needed that standardize measurement techniques and would
      allow accurate comparisons across studies.

PMID- 9040689
TI  - High signal intensity on T2-weighted magnetic resonance imaging and cerebral
      hemodynamic reserve in carotid occlusive disease.
AB  - BACKGROUND AND PURPOSE: The importance of MR imaging in carotid artery disease is
      unclear. We evaluated the sensitivity and specificity of the high signal
      intensity changes on MR images for diagnosis of hemodynamically compromised
      unilateral internal carotid artery disease. METHODS: We evaluated the association
      of high signal intensities on T2-weighted MR images with changes in cerebral
      perfusion reserve measured using 99mTc-hexamethylpropyleneamine oxime single
      photon emission CT and acetazolamide in 23 patients. RESULTS: Eleven patients had
      a type I response (normal flow and normal perfusion reserve), 8 patients had a
      type II response (normal flow and decreased perfusion reserve), and 4 patients
      had a type III response (decreased flow and decreased perfusion reserve). High
      signal intensities in the centrum semiovale (11/12) and/or posterior
      periventricular white matter (6/12) were frequently seen in the hemodynamically
      compromised groups. Extensive high signal intensities were associated with
      severely impaired cerebral circulation. MR imaging had high sensitivity (0.92)
      and specificity (1.0) in predicting hemodynamically compromised patients when we
      used the presence of T2 high intensity in the centrum semiovale as a criterion.
      CONCLUSIONS: The centrum semiovale T2 hyperintensities lateralized to the side of
      carotid occlusion are specific and sensitive for the presence and severity of
      hemodynamic compromise from carotid occlusive disease.

PMID- 9040690
TI  - Prevalence and time course of microembolic signals in patients with acute stroke.
      A prospective study.
AB  - BACKGROUND AND PURPOSE: Cerebral emboli can be identified by the presence of
      typical microembolic signals (MES) in transcranial Doppler (TCD) spectral curves.
      The usefulness of this technique was studied by evaluating the prevalence and
      time course of MES in patients with acute stroke. In addition, we examined the
      influence of anticoagulation therapy on the occurrence of MES. Another study
      objective was to identify the value of MES in elucidation of the underlying
      pathology of cerebral ischemia in patients with acute stroke. METHODS: We used
      bilateral TCD monitoring of the middle cerebral artery to search for microemboli
      in 100 patients with acute nonhemorrhagic stroke in the anterior circulation.
      Monitoring time was for 30 minutes at admission (examination I), after 24 hours
      (examination II), and again after 48 hours (examination III). RESULTS: Twenty-two
      of the 100 patients had to be excluded from the study after examination 1 because
      retrospectively they did not fulfill the inclusion criterion or because they had
      an insufficient bone window. Forty of the patients (51%) showed MES during at
      least one of the three TCD examinations. In 9 of the 47 patients without MES
      during examination I (19%), MES could be recorded subsequently during
      examinations II and III. A statistically significant decrease in the prevalence
      of MES occurred between examinations I and III (P = .01). The frequency of MES in
      a single patient decreased between examinations I and II but increased again in
      examination III, although it did not reach the initial level. Prevalence of MES
      was the highest during the period up to 6 hours after the onset of symptoms.
      However, even at > 72 hours after the onset of symptoms, a substantial number of
      MES could be recorded. In 18 of the 21 patients with carotid artery stenosis or
      occlusion who showed MES (86%), these signals occurred ipsilateral to the
      affected carotid artery. In 5 of the 13 patients with MES and a potential cardiac
      source of embolism (38%), MES were observed bilaterally. Forty-one patients were
      without anticoagulation treatment at the time of examination: 19 of these
      patients (46%) presented with MES. In contrast, of the 37 patients receiving
      anticoagulation treatment at the time of the first examination, MES could be
      recorded in only 12 (32%). CONCLUSIONS: Microemboli are a frequent phenomenon in
      patients with acute stroke arising from a variety of causes, both in the very
      early stages and several days after the onset of symptoms. The prevalence of MES
      decreases significantly over time. MES occur more frequently in patients with
      carotid artery disease than in patients with a potential cardiac source of
      embolism. Ipsilateral MES are frequent in patients with carotid artery disease,
      whereas bilateral MES are suggestive of a cardioembolic origin. Anticoagulation
      treatment appears to decrease the prevalence of MES, but microemboli still occur
      in patients receiving intravenous therapy with heparin. Because MES occur
      intermittently, TCD examinations should be repeated several times, even in
      patients without MES in the first examination, and long-term monitoring equipment
      is necessary.

PMID- 9040691
TI  - Inhibition of PDGF-mediated proliferation of vascular smooth muscle cells by
      calcium antagonists.
AB  - BACKGROUND AND PURPOSE: The mechanism by which calcium antagonists (CAs) inhibit
      proliferation in vascular smooth muscle cells (VSMCs) is not yet fully
      understood. We investigated the effects of four CAs (clentiazem, verapamil,
      diltiazem, and nifedipine) on signal transduction pathways activated by platelet
      derived growth factor (PDGF). To determine these effects, the levels of inositol
      phosphates (IPs), protein kinase C (PKC), and the induction of the transcription
      factor activator protein-1 (AP-1) were measured. METHODS: The mitogenic effect of
      PDGF on VSMCs was measured by [3H]thymidine incorporated into DNA. IP production
      was monitored by [3H]myo-inositol incorporation. PKC activation was determined by
      measurement of myristoylated, alanine-rich C kinase substrate (MARCKS)
      phosphorylation in digitonin-permeabilized VSMCs. The induction of AP-1 complex
      was detected by electrophoretic mobility shift assays. RESULTS: Each CA
      significantly inhibited the [3H]thymidine incorporation into DNA in unstimulated
      cells. Similar significant decreases in [3H]thymidine incorporation by CAs were
      observed when cells were stimulated by rPDGF-BB. The phosphorylation of MARCKS
      mediated by rPDGF-BB was significantly reduced by each CA. Clentiazem and
      verapamil significantly reduced the expression of AP-I induced by rPDGF-BB (P <
      .01, P < .05). Clentiazem also significantly reduced the expression of AP-1
      induced by rPDGF-AB (P < .05). CONCLUSIONS: PDGF-mediated proliferation of VSMCs
      correlates with activation of PKC but not with induction of the AP-1 complexes.
      In addition, our results suggest that CAs block proliferation of VSMCs by
      inhibiting DNA synthesis, possibly via PKC.

PMID- 9040692
TI  - Unruptured intracranial vertebral artery dissection. Clinical course and serial
      radiographic imagings.
AB  - BACKGROUND AND PURPOSE: Intracranial vertebral artery dissection is an
      increasingly recognized cause of stroke. However, little is known about its
      natural history and clinical manifestations, and appropriate management protocol
      has not yet been established. This study was performed to clarify its clinical
      course and determine the best management protocol. METHODS: This study is a
      retrospective clinical and radiographic review of 11 patients with 13 lesions who
      presented between 1990 and 1996. Patients with a history of trauma and those who
      presented with subarachnoid hemorrhage were excluded. The 11 patients comprised
      seven men and four women, who ranged in age from 34 to 71 years, with a mean age
      of 47 years. Ten patients presented with ischemic symptoms. RESULTS: Although
      recurrent ischemic attacks were observed in two patients, most (90%) subsequently
      made a good recovery and returned to their previous lifestyle. Five arteries
      showed the typical "string sign" or "pearl and string sign" on initial
      angiography. They changed in the follow-up examinations, which demonstrated
      either resolution of the stenosis or progression to complete occlusion. In
      contrast, the angiographic signs of complete occlusion (three arteries) or
      aneurysmal dilatation without luminal stenosis (four arteries) remained unchanged
      during the observation period of 5 months to 2.5 years. MRI was a sensitive tool
      for diagnosing intracranial vertebral artery dissection; intramural thrombus and
      intimal flap were the two major findings. MR angiography was also useful for
      demonstrating abnormalities of the arterial signal column such as pseudolumen or
      aneurysmal dilatation. CONCLUSIONS: The natural history of unruptured
      intracranial vertebral artery dissection seems relatively benign, with a high
      probability (62%) of spontaneous angiographic cure. Some persistent aneurysmal
      dilatation may be amenable to intravascular coil embolization.

PMID- 9040693
TI  - Human vascular endothelium heterogeneity. A comparative study of cerebral and
      peripheral cultured vascular endothelial cells.
AB  - BACKGROUND AND PURPOSE: Hormones, neurotransmitters, and autacoids play a key
      role in the regulation of vascular tone as a result of their interaction with the
      endothelium. The aim of this study was to compare selected properties of three
      human endothelial cell lines isolated from cerebral pial arteries (PEC) and two
      peripheral vessels, the superficial temporal (SEC) and omental (OEC) arteries.
      METHODS: Intracellular free calcium concentration ([Ca2+]i) and receptor protein
      expression were measured in characterized primary cultures of human endothelial
      cells. RESULTS: All cell lines labeled positively for factor VIII/von Willebrand
      factor. Growth rate and constitutive release of endothelin-1, expressed as a
      function of protein, were both significantly lower in cerebral cells (PEC) than
      in endothelial cells derived from peripheral vessels. Basal [Ca2+]i measured with
      the fluorescent calcium indicator fura 2-AM (2 mumol/L) did not differ in either
      of the three cell lines. Although PEC responded to endothelin-1 (0.1 mumol/L) and
      vasoactive intestinal peptide (1 mumol/L) by a twofold to threefold increase in
      [Ca2+]i, OEC were unresponsive to these peptides. Moreover, the calcium response
      to alpha-thrombin (10 nmol/L) was greater in cerebral (PEC) than in peripheral
      (SEC, OEC) endothelial cells, while bradykinin (100 nmol/L) increased [Ca2+]i to
      a similar level in all three cell types. CONCLUSIONS: This study demonstrates
      that endothelial cells from different sites of the vasculature exhibit different
      growth rates and vary in their response to agonists.

PMID- 9040694
TI  - Phagocytic response in photochemically induced infarction of rat cerebral cortex.
      The role of resident microglia.
AB  - BACKGROUND AND PURPOSE: In this study we assessed the relative extent to which
      resident microglia and blood-borne macrophages contribute to the population of
      phagocytes after focal infarction of the rat cortex. METHODS: Focal cerebral
      infarction was induced in rats by photothrombosis after hematogenous macrophages
      were depleted by means of liposomes containing dichloromethylene diphosphonate.
      The phagocytic activation of microglia and macrophages was monitored by
      immunocytochemistry with the antibody ED1. RESULTS: In both macrophage-depleted
      rats and controls, ED1+ phagocytes bordered the infarct to the same extent at day
      3 after photothrombosis. By contrast, at day 6 after photothrombosis ED1+
      phagocytes in control rats greatly outnumbered those in macrophage-depleted rats.
      With the use of the antibody Ox42 directed against the CR3 receptor on the
      surface of microglia, it was possible to selectively document the transition of
      resident microglia into stellate and ameboid phagocytic microglia during the
      first 6 days after photothrombosis in the absence of bloodborne macrophages.
      CONCLUSIONS: The initial phagocytic response after focal brain ischemia is an
      intrinsic property of the nervous system mainly performed by resident microglia.
      The majority of hematogenous macrophages are recruited secondarily to participate
      in the removal of necrotic tissue.

PMID- 9040695
TI  - Medical therapy for intracerebral hematoma with the gamma-aminobutyric acid-A
      agonist muscimol.
AB  - BACKGROUND AND PURPOSE: No therapy has been rigorously proven effective for
      intracerebral hematoma, although surgery is frequently used for some types of
      lobar hemorrhages. Since intracerebral mass causes significant ischemia in
      surrounding brain, we reasoned that anti-ischemia therapy might improve outcome
      after experimental hematoma. METHODS: We stereotaxically injected varying doses
      of bacterial collagenase into the caudate nucleus of rats. Four hours later we
      administered intravenously 2 mg/kg muscimol, a potent agonist of the gamma
      aminobutyric acid-A receptor (n = 20); 1 mg/kg MK-801, an antagonist of the N
      methyl-D-aspartate receptor (n = 17); or saline (n = 28). Forty-eight hours after
      collagenase injection we rated each animal using a standard rodent neurological
      examination. The ratings were compared with the amounts of injected collagenase
      by the quantal bioassay procedure. Brains were then prepared for histomorphometry
      and brain volumes estimated. RESULTS: We found that the ED50 for collagenase
      (amount of enzyme that renders 50% of the subjects abnormal) was 0.77 +/- 0.09 U
      in saline-treated subjects. Treatment with muscimol significantly increased the
      ED50 to 1.2 +/- 0.21 U, for a potency ratio of 1.55 +/- 0.34 (t = 1.7, P < .05).
      MK-801 did not affect outcome. Volume of hematoma was significantly correlated
      with amount of injected collagenase (n = 33, r = .64, P < .001). Volumes of basal
      ganglia and white matter were significantly reduced by hemorrhage, and muscimol
      partially ameliorated this. CONCLUSIONS: We conclude that muscimol significantly
      improves neurological outcome after intracerebral hematoma.

PMID- 9040696
TI  - Effect of subarachnoid hemorrhage on cerebral vasodilatation in response to
      activation of ATP-sensitive K+ channels in chronically hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Cerebral vasodilatation in response to aprikalim, an
      opener of ATP-sensitive K+ channels, is selectively augmented after subarachnoid
      hemorrhage (SAH). Vasodilatation in response to activation of ATP-sensitive K+
      channels, however, is impaired during chronic hypertension. Hypertension may
      contribute to a worse outcome after SAH, but the nature of the relationship
      between hypertension and SAH is uncertain. In the present study we examined
      responses of the basilar artery to aprikalim after SAH in normotensive Wistar
      Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP).
      METHODS: In anesthetized WKY and SHRSP, we measured changes in diameter of the
      basilar artery in response to aprikalim and papaverine using a cranial window 2
      days after injection of 0.3 mL saline or autologous blood into the cistema magna.
      RESULTS: Under control conditions, aprikalim (0.1 to 1 mumol/L) and papaverine
      (10 to 100 mumol/L) produced dilatation of the basilar artery. After SAH,
      responses to aprikalim were not significantly altered in WKY and were markedly
      increased in SHRSP compared with saline-injected control rats. In contrast,
      vasodilator responses to papaverine were not changed by SAH in either WKY or
      SHRSP, suggesting that augmented vasodilatation in response to aprikalim after
      SAH was selective. CONCLUSIONS: Responses of the basilar artery to aprikalim were
      greatly augmented in SHRSP after SAH. Because vasodilator responses to many
      stimuli are impaired after SAH and cerebral vasodilator responses to several
      stimuli are impaired by chronic hypertension, augmented responses to activation
      of K+ channels despite the presence of hypertension are unusual.

PMID- 9040697
TI  - Cerebral aneurysms arising at nonbranching sites. An experimental Study.
AB  - BACKGROUND AND PURPOSE: The origin and pathogenesis of cerebral aneurysms arising
      at nonbranching sites are not clear. Using our animal model to induce cerebral
      aneurysms in rats, we examined induced aneurysms that developed at nonbranching
      sites. METHODS: In 35 Sprague-Dawley rats, the left common carotid artery was
      ligated and renal hypertension was produced to induce cerebral aneurysms. Twelve
      months later, the circle of Willis was carefully examined under a dissecting
      microscope. RESULTS: Other than cerebral aneurysms at branching sites of the
      circle of Willis, aneurysmal bulges developing at nonbranching sites were found
      in the proximal portion of the posteriorice rebral artery (P1) on the side of
      carotid ligation, which supposedly acted as a major collateral pathway after the
      ligation, in 19 of 35 treated rats. A total of 30 lesions were found in these 19
      rats, and they were classified into fusiform aneurysms (22 lesions) involving the
      entire vessel wall for a short distance and saccular aneurysms (8 lesions)
      involving only a part of the wall and expanding laterally from the vessel wall.
      These P1s became larger in caliber and more tortuous after ligation. Aneurysms
      developed more frequently in proportion to these changes in these vessels.
      Moreover, most aneurysms in these vessels developed at or near the curvatures.
      All of the lateral aneurysms were found on the lateral wall of the curvatures of
      the vessels. CONCLUSIONS: The present findings indicate that cerebral aneurysms
      at nonbranching sites and saccular aneurysms at branching sites can occur under
      the same etiologic conditions. The site of origin is strongly related to
      hemodynamic stress.

PMID- 9040698
TI  - High glucose concentrations dilate cerebral arteries and diminish myogenic tone
      through an endothelial mechanism.
AB  - BACKGROUND AND PURPOSE: Diabetes is associated with cerebrovascular disease and
      impaired autoregulation of cerebral blood flow. The purpose of this study was to
      determine the effect of acute glucose exposure on basal tone and myogenic
      reactivity of isolated rat cerebral arteries. METHODS: Posterior cerebral
      arteries (PCAs, n = 38) were dissected from male Wistar rats and mounted on glass
      cannulas in a system that allowed control of transmural pressure (TMP) and
      measurement of lumen diameter. Arteries were exposed to various concentrations of
      glucose, and the amount of basal tone and reactivity to TMP was measured. The
      effect of elevated glucose on cerebral endothelial modulation of basal tone was
      determined by mechanical denudation and the use of inhibitors of both nitric
      oxide and prostaglandin synthesis. RESULTS: Arteries exposed to 44 versus 5.5
      mmol/L glucose developed significantly less intrinsic tone (percent tone, 2 +/-
      1% versus 28 +/- 2%; P < .01) and responded passively to increases in TMP.
      Preexisting tone present in 5.5 mmol/L glucose was eliminated on exposure to 44
      mmol/L glucose, which decreased tone from 30 +/- 5% to 5 +/- 4% (P < .01).
      Glucose-induced dilations were concentration dependent such that half-maximal
      responses were obtained at 25 +/- 2 mmol/L. Endothelial removal abolished this
      effect, and the amount of tone was similar in 5.5 versus 44 mmol/L glucose
      (percent tone, 46 +/- 6% versus 49 +/- 5%; P > .05), as did inhibition of nitric
      oxide production with 0.3 mmol/L nitro-L-arginine (percent tone, 52 +/- 4% versus
      46 +/- 3%; P > .05); however, blockade of the cyclooxygenase pathway with
      indomethacin (10(-5) mmol/L) only partially inhibited the dilation to glucose
      (percent tone, 32 +/- 3% in 5.5 mmol/L versus 12.4 +/- 3% in 44 mmol/L; P < .01).
      CONCLUSIONS: Acute glucose exposure dilates arteries with intrinsic tone and
      impairs cerebrovascular reactivity to TMP via an endothelium-mediated mechanism
      that involves nitric oxide and prostaglandins.

PMID- 9040700
TI  - Spreading of vasogenic edema and cytotoxic edema assessed by quantitative
      diffusion and T2 magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC) of water should
      be sensitive to the cytotoxic edema triggered by energy failure during ischemia.
      Elevated values of T2. the nuclear MR transverse relaxation time of water, seen
      on T2 nuclear MR images detect vasogenic edema and infarcted areas. The temporal
      and spatial changes in ADC and T2 abnormalities after occlusion of the middle
      cerebral artery (MCAO) were therefore estimated by these two quantitative
      techniques. METHODS: Permanent MCAO was performed on rats. Quantitative ADC and
      T2 maps of brain water were obtained, from which the ischemic volumes were
      calculated at various times up to 48 hours after MCAO. RESULTS: The areas of
      decreased ADC represented 36 +/- 7% of the final infarct volume (24 hours) at 0.5
      hours and 64 +/- 4% at 5 hours after MCAO, suggesting that there is recruitment
      of peripheral areas with disturbed energy metabolism and cytotoxic edema. The ADC
      and T2 contours closely matched at 3.5, 24, and 48 hours after MCAO. CONCLUSIONS:
      T2 imaging can assess ischemic insults as well as ADC imaging, but only 3.5 hours
      after the onset of ischemia. Assessment of edematous swelling (approximately
      24.5% of total infarcted volume) demonstrates that ADC and therefore T2 imaging
      detect all the tissue that will become infarcted approximately 7 hours after
      occlusion. The spread of ADC and T2 abnormalities would therefore stop at
      approximately 7 hours, and any further increase in volume observed on the images
      would be mainly due to edematous swelling.

PMID- 9040699
TI  - Prolongation and enhancement of postischemic c-fos expression after fasting.
AB  - BACKGROUND AND PURPOSE: A rapid but transient expression of c-fos after cerebral
      ischemia has been extensively documented. However, the mechanism of this
      induction and whether induction of c-fos is neuroprotective or detrimental to the
      brain after ischemia is presently not clear. Fasting before transient cerebral
      ischemia has been shown to reduce delayed neuronal necrosis and infarct volume.
      The purpose of the present study was to examine the effect of preischemic fasting
      for 24 hours on the expression of c-fos after transient focal cerebral ischemia.
      METHODS: Focal cerebral ischemia was induced by temporary occlusion of the right
      middle cerebral artery and both common carotid arteries for 60 minutes. Male Long
      Evans rats weighting 250 to 300 g were randomly divided into two groups: fed
      (control group) and food deprived for 24 hours (fasted group) before ischemic
      surgery. Infarct volumes were measured on the basis of triphenyltetrazolium
      chloride-delineated infarct areas, and plasma glucose levels were determined by
      the glucose oxidase method. Temporal and spatial expression of c-fos was assessed
      by Northern blot analysis, in situ hybridization, and immunohistochemistry.
      RESULTS: Fasting for 24 hours before 60 minutes of ischemia resulted in a 26.6%
      decrease in preischemic plasma glucose levels and a 74.5% reduction in infarct
      volumes in the fasted group compared with the control group. A rapid but
      transient induction of c-fos mRNA was observed in the ischemic cortex in control
      animals after 60 minutes of ischemia. Fasting not only prolonged but also
      enhanced the intensity of c-fos expression in the ischemic cortex. Regional c-fos
      expression was also different between these two groups. CONCLUSIONS: The results
      support the contention that c-fos expression may be compatible with its purported
      neuroprotective role in selected experimental paradigms. The signaling mechanisms
      underlying the effect of fasting and subsequent lowering of plasma glucose levels
      on postischemic c-fos expression remain to be explored.

PMID- 9040701
TI  - Protection with lubeluzole against delayed ischemic brain damage in rats. A
      quantitative histopathologic study.
AB  - BACKGROUND AND PURPOSE: Cerebral ischemia may lead to glutamate-induced
      excitotoxic damage in vulnerable brain areas. Lubeluzole is not an N-methyl-D
      aspartate antagonist but prevents postischemic increase in extracellular
      glutamate concentrations. The present study examined whether lubeluzole,
      administered after global incomplete ischemia in rats, is capable of preserving
      the structural integrity of CA1 hippocampus. METHODS: Ischemia was induced by
      bilateral carotid artery occlusion and severe hypotension for a duration of 9
      minutes. Delayed neuronal cell death was histologically evaluated 7 days later.
      This was done by scoring acidophilic cell change and coagulative necrosis and by
      counting the number of surviving neurons in the CA1 subfield. Experiments were
      performed according to a paired design (13 animals per treatment group). RESULTS:
      Posttreatment with lubeluzole (0.31 mg/kg i.v. bolus at 5 minutes and 0.31 mg/kg
      i.v. infusion during 1 hour) resulted in significant neuroprotection. Whereas in
      the untreated rats there were 42 (median) viable neurons per millimeter CA1 layer
      in the left and 69 in the right hemisphere, in the drug-treated rats 99 viable
      neurons per millimeter were found in the left (P = .002) and 113 in the right
      hemisphere (P = .013). Histological scores, reflecting altered staining
      properties of the hippocampal cells, correlated strongly with the quantitative
      data, reflecting the structural integrity of CA1 pyramidal neurons. CONCLUSIONS:
      Lubeluzole, when administered after an ischemic insult in rats, protects
      vulnerable brain regions against delayed structural injury. The results support
      the potential clinical use of this new drug in stroke treatment.

PMID- 9040702
TI  - Role of potassium channels in relaxations of isolated canine basilar arteries to
      acidosis.
AB  - BACKGROUND AND PURPOSE: Concentration of hydrogen ions is an important regulator
      of cerebral arterial tone under physiological and pathological conditions.
      Previous studies demonstrated that in cerebral arteries, relaxations to
      hypercapnia are due to decrease in extracellular pH. The present study was
      designed to determine the role of potassium channels in mediation of cerebral
      arterial relaxations induced by extracellular acidosis. METHODS: Rings of canine
      basilar arteries without endothelium were suspended for isometric force
      recording. Acidosis (pH 7.3 to 7.0) was produced by incremental addition of
      hydrochloric acid (1.0N). The concentration of hydrogen ions was continuously
      monitored with a pH meter. RESULTS: During contractions to UTP, acidosis (pH 7.3
      to 7.0) induced pH-dependent relaxations. These relaxations were abolished in
      arteries contracted by potassium chloride (20 mmol/L). A nonselective potassium
      channel inhibitor, BaCl2 (10(-4) and 10(-4) mol/L), and an ATP-sensitive
      potassium channel inhibitor, glyburide (5 x 10(-6) mol/L), significantly reduced
      relaxations to acidosis. Furthermore, BaCl2 (10(-4) mol/L) and glyburide (5 x 10(
      6) mol/L) abolished relaxations to an ATP-sensitive potassium channel opener,
      cromakalim (10(-8) to 3 x 10(-5) mol/L). However, these potassium channel
      inhibitors did not affect relaxations to a voltage-dependent calcium channel
      inhibitor, diltiazem (10(-8) to 10(-4) mol/L), and glyburide (5 x 10(-6) mol/L)
      did not alter relaxations to a nitric oxide donor, SIN-1 (10(-9) to 10(-4)
      mol/L). A calcium-activated potassium channel inhibitor, charybdotoxin (10(-7)
      mol/L), and a delayed rectifier potassium channel inhibitor, 4-aminopyridine (10(
      3) mol/L), did not affect relaxations to acidosis. CONCLUSIONS: These results
      suggest that extracellular acidosis causes relaxations of cerebral arteries in
      part by activation of potassium channels. ATP-sensitive potassium channels appear
      to contribute to acidosis-induced decrease in cerebral arterial tone.

PMID- 9040703
TI  - Neuroprotection with NBQX in rat focal cerebral ischemia. Effects on ADC
      probability distribution functions and diffusion-perfusion relationships.
AB  - BACKGROUND AND PURPOSE: We have previously shown that treatment with glutamate
      receptor antagonists after focal ischemia can partially reverse acute lesions
      measured with diffusion-weighted MRI. The goal of this study was to examine the
      quantitative nature of these effects of neuroprotection. METHODS: Rats were
      subjected to permanent occlusion of the middle cerebral artery under halothane
      anesthesia and treated with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline
      (NBQX) (30 mg/kg IP; two doses given immediately after ischemia and 1 hour after
      ischemia) or given injections of saline. Diffusion-weighted MRI scans were
      performed to map the changes in water diffusivity during the first 3 hours after
      ischemia. Apparent diffusion coefficients (ADCs) within the ischemic hemisphere
      were calculated, and ischemic changes were expressed as absolute reductions and
      as a percentage of contralateral mean values. Relative perfusion deficits in the
      ischemic hemisphere were assessed with dynamic MRI of transient changes in
      transverse relaxation rates (delta R2*). RESULTS: Analysis with ADC probability
      distribution functions showed that focal ischemia was present with gradients in
      ADC reductions emanating from the center to the periphery of the lesion. Ischemic
      evolution in control rats was manifested as a progressive shift of the
      probability distribution functions over time. NBQX treatment resulted in a
      reverse shift of these probability functions. By 3 hours after occlusion,
      probability distribution functions were significantly improved in treated rats (P
      < .05). Because of the temporal evolution of the probability distribution
      functions, ADC thresholds that correlated with histological outcomes of
      infarction changed over time. NBQX did not alter the cerebral perfusion index,
      measured as delta R2* peak values. CONCLUSIONS: The results indicate that ADC
      probability distribution functions can be used to quantitatively evaluate the
      effects of neuroprotective treatment on the gradients of injury in focal cerebral
      ischemia. The probability functions also allow for intrasubject comparisons and
      may therefore be useful for exploring therapeutic windows.

PMID- 9040704
TI  - Selective impairment of response to acetylcholine after ischemia/reperfusion in
      mice.
AB  - BACKGROUND AND PURPOSE: We previously reported that the endothelium-dependent
      dilation of pial arterioles by either topical acetylcholine (ACh) or bradykinin
      (BK) was markedly inhibited after 10 minutes of near total ischemia after
      bilateral carotid occlusion. The present study tests the responses after 10
      minutes of reperfusion and investigates the effect of either oxygen or oxygen
      radical scavengers on the results. METHODS: Mice were subjected to bilateral
      carotid ligation or sham ligation. Pial arteriolar diameters were monitored by an
      image-splitting technique at a craniotomy site. In separate studies, the
      responses to topically suffused ACh, BK, or sodium nitroprusside (SNP) were
      tested before ischemia. After 10 minutes of ischemia and 10 minutes of
      reperfusion, the response was assessed again. Sham-operated mice were observed in
      each study. Cerebral blood flow was continuously monitored with a laser-Doppler
      technique. Additional separate studies were conducted as follows: presence of
      superoxide dismutase plus catalase during ischemia and reperfusion, or increase
      in the inspired oxygen (arterial oxygen) and oxygen in suffusate. RESULTS: The
      response to ACh was significantly impaired after 10 minutes of reperfusion. The
      responses to BK and SNP were unaffected. Radical scavengers failed to influence
      the impaired response to ACh. Elevations of arterial and suffusate oxygen levels
      to over 300 mm Hg failed to prevent the impairment. CONCLUSIONS: After 10 minutes
      of reperfusion, a selective impairment of the response to ACh remains. The
      response to another endothelium-dependent dilator, BK, recovered, and the
      response to endothelium-independent SNP was unaffected. Because neither radical
      scavengers nor oxygen altered the outcome with respect to ACh, I suggest that
      neither radical generation nor hypoxia accounts for the selective impairment of
      dilation by ACh. Rather, I hypothesize that reduced shear during ischemia
      diminishes the ability of the endothelium to synthesize and/or release the
      endothelium-derived relaxing factor for ACh. I hypothesize further that this
      impaired release or synthesis persists throughout the 10-minute period of
      reperfusion.

PMID- 9040705
TI  - Infection-associated cervical artery dissection. Three cases.
AB  - BACKGROUND: The pathogenesis of cervical artery dissection remains unknown.
      Infection-mediated damage of the arterial wall may be one contributing mechanism.
      We present three male patients with respiratory infection prior to cervical
      artery dissection. CASE DESCRIPTIONS: Case 1: During an upper respiratory tract
      infection, a 49-year-old patient developed bilateral carotid and vertebral artery
      dissection with complete vessel restitution. Case 2: Within 3 years, a 40-year
      old patient experienced two episodes of bilateral internal carotid artery
      dissection, both preceded by febrile upper respiratory tract infection. Case 3: A
      52-year-old patient developed right-sided and, 2 years later, left-sided internal
      carotid artery dissection, each following upper respiratory tract infection.
      CONCLUSIONS: Infection may be a trigger factor in the pathogenesis of cervical
      artery dissection.

PMID- 9040706
TI  - Myxoma in the carotid artery. Myxomatous occlusion of internal carotid artery.
AB  - BACKGROUND: We describe a patient with an unusual cause of internal carotid
      artery occlusion resulting in a stroke. CASE DESCRIPTION: A 41-year-old woman
      presented with a typical acute right middle cerebral artery territory infarct.
      Her hematological and cardiological status was assessed, including all
      extracranial vessels. Carotid angiography and a biopsy were performed of the
      occluded right internal carotid artery and demonstrated a myxoma. Cardiac
      investigations to determine the source of the myxoma, including transthoracic and
      transesophageal echocardiograms, CT and yo-yo CT scans, and MRI of the heart,
      were normal. No residual tumor or potential source of the tumor was found.
      CONCLUSION: The cause of stroke was a myxomatous occlusion of the right internal
      carotid artery. An entire cardiac tumor may have embolized with no detectable
      residual tumor in the heart; alternatively, a myxoma may have originated as a
      primary tumor in the carotid artery. To our knowledge, no primary myxoma has been
      reported to have originated in a blood vessel.

PMID- 9040708
TI  - Performance of the unaffected hand after stroke.

PMID- 9040707
TI  - Status of risk factors for dementia associated with stroke.
AB  - BACKGROUND: Cognitive impairment associated with vascular disease may be the only
      preventable form of dementia of late life. Identification of risk factors for
      dementia associated with stroke may be a prelude to improved intervention.
      SUMMARY OF REVIEW: I reviewed putative risk factors for dementia associated with
      stroke. These included demographic, atherogenic, stroke-related, and genetic
      factors. Key studies from the English literature were reviewed and graded
      according to quality of evidence ratings (classes I, II, and III). Although many
      of the cardiovascular disease risk factors are logical antecedents of dementia
      associated with stroke, age was the only factor that could be considered a well
      documented risk factor. CONCLUSIONS: We should continue to support efforts
      directed at primary stroke prevention and the brain-at-risk and predementia
      stages. Additional rigorous epidemiological study is needed to clarify risk
      factors for dementia associated with stroke.

PMID- 9040709
TI  - Use of the SF-36 questionnaire in cerebrovascular disease.

PMID- 9040710
TI  - The neurologist as neuroimager.

PMID- 9040711
TI  - Ischemic tolerance in the brain.

PMID- 9040712
TI  - A multicenter, randomized, double-blind, placebo-controlled trial of influenza
      immunization in multiple sclerosis.
AB  - We determined the effect of influenza vaccine in patients with
      relapsing/remitting MS. Considerable controversy surrounds the question of
      whether to administer influenza vaccines to MS patients. Prevention of a febrile
      viral illness is clearly desirable in MS, and previous studies suggest that
      immunization is safe. Despite this, many clinicians avoid vaccination because
      they fear precipitating an MS exacerbation. We conducted a multicenter,
      prospective, randomized, double-blind trial of influenza immunization in patients
      with relapsing/remitting MS. In the autumn of 1993, 104 patients at five MS
      centers received either standard influenza vaccine or placebo. Patients were
      followed for 6 months for evaluation of neurologic status and the occurrence of
      influenza. Influenza was operationally defined as fever > or = 38 degrees C in
      the presence of coryza, cough, or sore throat at a time when the disease was
      present in the community. Attacks were defined in the standard manner, requiring
      objective change in the examination. Patients were examined at 4 weeks and 6
      months after inoculation and were contacted by telephone at 1 week and 3 months.
      They were also examined at times of possible attacks but not when they were sick
      with flu-like illness. Three vaccine patients and two placebo patients
      experienced attacks within 28 days of vaccine (no significant difference).
      Exacerbation rates in the first month for both groups were equal to or less than
      expected from published series. The two groups showed no difference in attack
      rate or disease progression over 6 months. Influenza immunization in MS patients
      is neither associated with an increased exacerbation rate in the postvaccination
      period nor a change in disease course over the subsequent 6 months.

PMID- 9040713
TI  - HTLV-associated myelopathy in a cohort of HTLV-I and HTLV-II-infected blood
      donors. The REDS investigators.
AB  - OBJECTIVE: HTLV-I-associated myelopathy (HAM) is a slowly progressive spastic
      paraparesis caused by infection with human T-lymphotropic virus type I (HTLV-I).
      The prevalence of HAM among those infected with HTLV-I is poorly defined, and the
      association of a similar myelopathy with HTLV-II infection has not been
      confirmed. DESIGN: Cross-sectional examination of HTLV-I, HTLV-II, and control
      subjects from the baseline visit of a cohort study. SETTING/ SUBJECTS: Persons
      testing HTLV seropositive at the time of blood donation at five U.S. blood
      centers, their seropositive sex partners, and a matched control group of HTLV
      seronegative blood donors. MEASUREMENTS: HTLV-I and HTLV-II were differentiated
      by serology and/or polymerase chain reaction. All subjects received systematic
      neurologic screening examinations. RESULTS: A diagnosis of myelopathy was
      confirmed in four of 166 HTLV-I subjects (2.4%, 95% confidence interval 0.7%,
      6.1%) and in one of 404 HTLV-II subjects (0.25%, 95% confidence interval 0.0%,
      0.6%). None of the 798 controls had a similar myelopathy, although one had
      longstanding typical multiple sclerosis. CONCLUSIONS: Our data also suggest that
      HAM occurs more frequently among HTLV-I-infected subjects than reported by
      previous studies. The HTLV-II infected myelopathy patient identified in this
      cohort, together with three other case reports in the literature, implies a
      pathogenic role for this human retrovirus. The diagnosis of HTLV-associated
      myelopathy should be considered in cases of spastic paraparesis or neurogenic
      bladder when risk factors for HTLV-I or HTLV-II infection are present.

PMID- 9040714
TI  - Chronic inflammatory demyelinating polyneuropathy: clinical features and response
      to treatment in 67 consecutive patients with and without a monoclonal gammopathy.
AB  - We report the clinical and EMG details of 67 consecutive patients with strictly
      defined chronic inflammatory demyelinating polyneuropathy (CIDP) during a 4-year
      period and compare responses to treatment in patients with idiopathic CIDP (CIDP
      I) and CIDP with monoclonal gammopathy of uncertain significance (CIDP-MGUS).
      Patients were examined an average of 28 months after first symptoms. There were
      several variant presentations that still conformed to the clinical and
      electrophysiologic definitions of CIDP, including a pure motor syndrome (10%),
      sensory ataxic variant (12%), mononeuritis multiplex pattern (9%), paraparetic
      pattern (4%), and relapsing acute Guillain-Barre syndrome (16%). Pain was more
      frequent than in previous studies (42%). Conduction block was the commonest EMG
      abnormality (detected in at least one nerve in 73% of patients), but only 31% had
      a pure demyelinating neuropathy and the majority had some degree of axonal
      change. Patients with CIDP-MGUS had less severe weakness, greater imbalance, leg
      ataxia, vibration loss in the hands, and absent median and ulnar sensory
      potentials, but were as likely as CIDP-I patients to respond to plasma exchange.
      Seventeen of 44 patients (39%) with idiopathic CIDP improved for at least 2
      months with an initial therapy. Although the response rates among plasma
      exchange, IVIG, and steroids were similar, functional improvement (Rankin score)
      was greatest with plasma exchange. Of 26 patients who failed to respond to an
      initial therapy, 9 (35%) benefited from an alternative treatment, and of the 11
      who required a third modality 3 (27%) improved. Overall, 66% responded to one of
      the three main therapies for CIDP.

PMID- 9040715
TI  - Pain in Guillain-Barre syndrome.
AB  - OBJECTIVES: To determine the character, intensity and frequency of pain in
      Guillain-Barre syndrome (GBS) and to evaluate the response to treatment. DESIGN:
      A prospective longitudinal study. SETTING: Academic hospital-based practices.
      PATIENTS: Fifty-five consecutive patients with GBS. INTERVENTIONS: Patients were
      evaluated on admission and at 2, 4, 8, 16, and 24 weeks. MAIN OUTCOME MEASURES:
      Character of pain, pain intensity using Visual Analogue Scale ([VAS] 0 to 10 cm)
      and Present Pain Intensity of McGill Pain Questionnaire, pain relief (VAS 0 to 10
      cm), Disability Grading Scale for GBS. RESULTS: Forty-nine patients (89.1%)
      described pain during the course of their illness. On admission, mean pain
      intensity (VAS) was 4.7 +/- 3.3. However, 26 patients (47.3%) described pain that
      was either distressing, horrible, or excruciating (mean VAS, 7.0 +/- 2.0). The
      most common pain syndromes observed were deep aching back and leg pain and
      dysesthetic extremity pain. Pain intensity on admission correlated poorly with
      neurologic disability on admission (r = 0.26, p = 0.06) and throughout the period
      of study (r < 0.20, p > 0.10). Forty-one patients (74.5%) required opioid
      analgesics, with 16 (29.0%) receiving parenteral morphine to provide adequate
      pain relief. CONCLUSIONS: Moderate to severe pain is a common and early symptom
      of GBS and requires aggressive treatment. Pain intensity on admission is not a
      predictor of poor prognosis. Back and leg pain usually resolves over the first 8
      weeks, but dysesthetic extremity pain may persist longer in 5 to 10% of patients
      despite motor recovery and the use of adjuvant analgesics.

PMID- 9040716
TI  - Development and preliminary validation of a pain measure specific to neuropathic
      pain: the Neuropathic Pain Scale.
AB  - Neuropathic pain syndromes are commonly seen in clinical practice and are
      frequently used as pain models in testing new therapies. However, no pain scale
      exists with the primary purpose to measure pain in neuropathic syndromes. This
      paper describes the development and preliminary validation of the Neuropathic
      Pain Scale (NPS), which is designed to assess distinct pain qualities associated
      with neuropathic pain. Results support the discriminant and predictive validity
      of the NPS items. Moreover, the NPS items appear to be sensitive to treatments
      known to impact neuropathic pain. These findings provide support for the further
      development of the NPS.

PMID- 9040717
TI  - Inflammatory myopathy in thyrotoxicosis.
AB  - A 45-year-old man with a 3-month history of episodic muscle weakness, MRC grade
      4/5 symmetric hip flexor weakness, elevated CK, and an inflammatory myopathy was
      found to have elevated free thyroxine and T3. Treatment with carbimazole resulted
      in complete resolution of symptoms and return of muscle power to normal. A repeat
      biopsy revealed resolution of the inflammatory endomysial infiltrate and an
      absence of necrosis. Complete clinical and pathologic resolution of a
      thyrotoxicosis-associated inflammatory myopathy without steroid therapy has not
      been previously described. The favorable outcome experienced by this patient
      indicates that steroids may not be necessary in thyrotoxicosis-associated
      inflammatory myopathy.

PMID- 9040718
TI  - Crack cocaine use and stroke in young patients.
AB  - BACKGROUND AND PURPOSE: Numerous case series have proposed a relationship between
      "crack" cocaine use and stroke. We performed a retrospective case control study
      at a large inner-city public hospital to determine the relationship between crack
      use and stroke among young persons. METHODS: We reviewed records of all patients
      aged 20 to 39 years with a diagnosis of stroke, and of controls selected from
      patients with noncocaine-related diagnoses, admitted from January 1990 through
      June 1994. We collected information regarding cocaine use, time of last use,
      route of use, and the results of urine toxicologic studies. We performed backward
      stepwise logistic regression analyses to determine the association of crack use
      at any time and acute crack use (defined as use within 48 hours prior to
      presentation) with stroke and stroke subtypes. RESULTS: Among patients with
      information regarding presence or absence of crack use (66 of 144 stroke patients
      and 99 of 147 controls), crack use at any time was not associated with stroke
      (odds ratio [OR] = 0.7, 95% CI 0.4-1.8) or cerebral infarction (OR = 0.5, 95% CI
      0.2-1.2). Among patients providing temporal information regarding crack use,
      acute crack use was not associated with stroke (OR = 1.9, 95% CI 0.7-5.1) or
      cerebral infarction (OR = 1.2, 95% CI 0.4-3.8). CONCLUSIONS: Crack use at any
      time or acute crack use was not significantly associated with stroke or cerebral
      infarction in our patient population.

PMID- 9040719
TI  - Validation of the ACAS TIA/stroke algorithm.
AB  - BACKGROUND AND PURPOSE: An easily administered questionnaire and algorithm
      classifying transient ischemic attacks (TIAs) or strokes, and also their
      distribution, could be invaluable for identifying endpoints in epidemiologic
      studies or clinical trials of prevention and therapy of cerebral ischemia. The
      Asymptomatic Carotid Atherosclerosis Study (ACAS) devised a symptom-based
      questionnaire and algorithm for detecting events in the trial. The purpose of
      this study was to determine sensitivity, specificity, and agreement rates of the
      questionnaire and algorithm against diagnoses of a panel of cerebrovascular
      disease authorities. METHODS: Three hundred eighty-one men and women at eight
      medical centers reported symptoms of stroke, TIA, or other neurologic illness.
      The questionnaire was administered by trained interviewers and the responses were
      analyzed using the algorithm. A standardized neurologic examination was performed
      by a neurologist. Data were submitted to two or more external reviewers.
      Sensitivity, specificity, and the kappa statistic (kappa) were used to evaluate
      the relationship between the algorithm and the external reviewers' diagnosis.
      RESULTS: Of the 381 reviews, 196 were diagnosed as TIA or stroke by the external
      panel. The algorithm's agreement with the diagnosis of TIA or stroke was 80.1%,
      and kappa was 0.60. Sensitivity was 87.8%, and specificity was 71.9%. CONCLUSION:
      While statistical agreement rates depend on the method of sample selection, the
      algorithm has a high agreement with an external panel of experts and is a
      sensitive tool for event detection. The lower specificity indicates that careful
      neurologic evaluation may be required to confirm or refute events identified by
      the screening algorithm.

PMID- 9040720
TI  - Cerebrospinal fluid creatine kinase BB isoenzyme activity and neurologic
      prognosis after cardiac arrest.
AB  - OBJECTIVE: To assess the relationship between CSF creatine kinase BB isoenzyme
      activity (CSF CKBB) and neurologic outcome after cardiac arrest in clinical
      practice. BACKGROUND: CSF CKBB reflects the extent of brain damage following
      cardiac arrest. METHODS: To help with prognosis, treating physicians ordered CSF
      CKBB tests on 474 patients over 7.5 years; 351 of these patients had experienced
      a cardiac arrest. Assays were performed in one laboratory using agarose
      electrophoresis. By chart review, we determined awakening status for all
      patients, defined as the patient having comprehensible speech or following
      commands. RESULTS: CSF CKBB was usually sampled 48 to 72 hours after cardiac
      arrest and was strongly associated with awakening (p < < 0.001). The median was 4
      U/l for 61 patients who awakened and 191 U/l for 290 who never awakened. For
      those who awakened, 75% of CKBB levels were < 24 U/l, and for those who never
      awakened, 75% were > 86 U/l. The highest value in a patient who awakened was 204
      U/l, a cutoff that yielded a specificity of 100% of never awakening but a
      sensitivity of forty-eight percent. Only nine patients who awakened had CSF CKBB
      values greater than 50 U/l, and none regained independence in activities of daily
      living. Only three unconscious patients were still alive at last contact, with
      follow-up of 63, 107, and 109 months. Using logistic regression, the probability
      of never awakening given a CSF CKBB result can be estimated as: 1/(1 + L), where
      L = e raised to (0.1267 - 0.0211 x CSF CKBB [U/l]). CONCLUSION: CSF CKBB
      measurement helps to estimate degree of brain damage and thus neurologic
      prognosis after cardiac arrest. However, results of this retrospective study
      could reflect in part a self-fulfilling prophecy.

PMID- 9040721
TI  - Long-term effects of tetrabenazine in hyperkinetic movement disorders.
AB  - Over the past 15 years we have treated 526 patients with severe hyperkinetic
      movement disorders with tetrabenazine (TBZ), a monoamine-depleting and a dopamine
      receptor-blocking drug. We report here the results in 400 patients with adequate
      follow-up. The response was rated on a scale of 1 to 5 (1 = marked improvement, 4
      = no response, 5 = worsening) and was assessed initially and at the last clinic
      visit. The average duration of TBZ treatment was 28.9 months (+/- 31.1; range,
      0.25 to 180 months). The global response rating of 1 (marked improvement) was
      recorded in 89.2% of 93 patients with tardive stereotypy, 83.3% of 12 with
      myoclonus, 82.8% of 29 with Huntington's disease, 80.5% of 82 with tardive
      dystonia, 79.3% of 29 with other movement disorders, 62.9% of 108 with idiopathic
      dystonia, and in 57.4% of 47 with Tourette's syndrome. The most common side
      effects included drowsiness (36.5%), parkinsonism (28.5%), depression (15.0%),
      insomnia (11.0%), nervousness or anxiety (10.3%), and akathisia (9.5%). The side
      effects were controlled with reduction in the dosage. TBZ is an effective and
      safe drug for the treatment of a variety of hyperkinetic movement disorders. In
      contrast to typical neuroleptics, TBZ has not been demonstrated to cause tardive
      dyskinesia.

PMID- 9040722
TI  - Cabergoline in the treatment of early Parkinson's disease: results of the first
      year of treatment in a double-blind comparison of cabergoline and levodopa. The
      PKDS009 Collaborative Study Group.
AB  - Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may
      provide continuous dopaminergic stimulation administered once daily. In this
      study, we randomized de novo Parkinson's disease (PD) patients to treatment with
      increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up
      to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability
      (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were
      considered indicative of clinical improvement. If 30% improvement was not
      achieved, levodopa/ carbidopa could be added on an open basis. Of the 208
      patients entered in the cabergoline group, 175 remained in the study for 1 year
      at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients
      entered were still on study after 1 year at a mean dose of 468 mg/d. The
      proportion of patients requiring additional levodopa/carbidopa increased in the
      cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at
      6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of
      patients showing clinical improvement did not differ significantly between the
      two groups, or between the subgroups on monotherapy, at any endpoint.
      Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline
      group and 87% of patients in the levodopa group were clinically improved at 1
      year (p = 0.189); the corresponding figures for the subgroup on monotherapy were
      79% in the cabergoline-treated patients and 86% in the levodopa-treated patients
      (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease
      Rating Scale Factor III scores in patients who remained on monotherapy up to 1
      year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group
      and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in
      76% of patients on cabergoline and in 66% of patients on levodopa. The severity
      profile for reported events was similar for the two agents. The results of this
      study indicate that cabergoline treatment for up to 1 year is only marginally
      less effective than levodopa in the proportion of patients who can be treated in
      monotherapy. More than 60% of de novo PD patients could be managed on cabergoline
      alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the
      combination therapy provided efficacy similar to that obtained with levodopa
      alone, with a relevant sparing of levodopa.

PMID- 9040724
TI  - Laryngeal deglutition movement in Parkinson's disease.
AB  - Laryngeal muscle function is defective in Parkinson's disease (PD) patients; the
      intrinsic group (vocal cords) is defective during phonation and the extrinsic
      group (laryngeal strap muscles) is slow during deglutition. There are no studies
      of vocal cord motility during deglutition in PD. We investigated laryngeal
      motility during deglutition in 71 patients with PD in a videofluoroscopic
      swallowing study. Patients were subdivided into two groups by the Hoehn and Yahr
      disability scale, stages II and III (n = 38) and stages IV and V (n = 33). At
      least one abnormality of laryngeal movement was present in 68 of 71 patients
      (95.8%); most patients had multiple abnormalities. There was statistically
      significant slowing of vertical laryngeal excursion; true vocal cord closure; or
      delayed, incomplete, or absent opening of the true vocal cords. Patients with
      more advanced disease manifested more deficits of laryngeal movement. Laryngeal
      dysmotility in PD may be related to defective descending basal ganglionic control
      of medullary deglutory and phonatory motor functions.

PMID- 9040723
TI  - Apomorphine responses in Parkinson's disease and the pathogenesis of motor
      complications.
AB  - We studied the contribution of basal ganglia circuitry downstream from the
      nigrostriatal dopaminergic system to the pathogenesis of levodopa associated
      motor complications by means of an apomorphine dose-response paradigm in 28
      parkinsonian patients grouped according to their clinical response to levodopa
      therapy. With progression from the dopa-naive to the severely fluctuating
      dyskinetic state, apomorphine response duration shortened, the dose-response
      slope steepened, and the therapeutic window narrowed. Because apomorphine acts
      independently of the integrity of presynaptic dopaminergic neurons, our results
      suggest that postsynaptic alterations account mainly for the appearance of
      response complications. The present findings support the possibility, raised by
      animal model studies, that motor response complications arise as a consequence of
      altered signal transduction mechanisms in striatal medium-sized neurons.

PMID- 9040725
TI  - Comparison of extrapyramidal features in 31 pathologically confirmed cases of
      diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson's
      disease.
AB  - OBJECTIVE: To compare the extrapyramidal features of pathologically confirmed
      cases of diffuse Lewy body disease (DLBD) and Parkinson's disease (PD).
      BACKGROUND: The proportion of pathologically confirmed cases of DLBD diagnosed
      clinically as PD is as high as 88%. Few papers focus specifically on the
      extrapyramidal features of DLBD. Further characterization of these features might
      facilitate antemortem diagnosis, in particular, distinguishing DLBD from PD.
      METHODS: Review of prospective and retrospective clinical data on a large series
      of pathologically diagnosed cases of DLBD (N = 31) and PD (N = 34) seen between
      1984 and 1995 at Columbia-Presbyterian Medical Center or the University of
      Rochester. RESULTS: Those with DLBD had an older mean age of onset (67.9 years)
      than PD (62.0 years) (z = 6.5, p < 0.0001). Rest tremor was more common in PD
      (85.0%) than DLBD (55.0%) (chi 2 = 4.3, p = 0.038). Myoclonus was more common in
      DLBD (18.5%) than PD (0%) (Fisher's p = 0.021). There were no differences in
      rigidity, bradykinesia, dystonia, or gaze palsies. Clinical response to levodopa
      may have been more common in PD (100%) than DLBD (70.0%) (Fisher's p = 0.059).
      The occurrence of any one of four clinical features (myoclonus, absence of rest
      tremor, no response to levodopa, or no perceived need to treat with levodopa) was
      10 times more likely in DLBD than PD (odds ratio = 10.29, 95% confidence interval
      = 2.58-41.11). CONCLUSIONS: We demonstrated that several clinical features
      distinguish DLBD from PD. These features, in combination with reported
      differences in cognitive and psychiatric manifestations, may be used for
      diagnostic purposes in distinguishing DLBD from PD in prospective longitudinal
      cohort studies of DLBD.

PMID- 9040726
TI  - Disappearance of motor tics after Wernicke's encephalopathy in a patient with
      Tourette's syndrome.
AB  - Tourette's syndrome (TS) is a disease characterized by multiple motor and vocal
      tics as well as behavioral abnormalities. The anatomic substrates of this
      syndrome are not defined. We report a 48-year-old man with TS in whom motor tics
      disappeared after the onset of a midbrain syndrome related to thiamine deficiency
      (Wernicke's encephalopathy). MRI study showed a lesion in the dorsal area of the
      midbrain. This case suggests that loops located in the midbrain tegmentum may
      influence the presence of motor tics in patients with TS.

PMID- 9040727
TI  - Survival of patients with pathologically proven multiple system atrophy: a meta
      analysis.
AB  - A systematic review of the neurologic literature identified 433 cases of
      pathologically proven multiple system atrophy over a 100-year period. Earlier
      case reports included patients younger in age with more frequent cerebellar
      involvement. Mean age of onset was 54.2 years (range 31 to 78) and survival was
      6.2 years (range 0.5 to 24). Survival analysis showed a secular trend from a
      median duration of 4.9 years for publications between 1887 and 1970 to 6.8 years
      between 1991 and 1994. Older age of onset was associated with shorter survival;
      the hazard ratio for patients with onset after 60 years was 1.8 (95% CI 1.4 to
      2.3) compared with patients between 31 and 49 years. Cerebellar features were
      associated with marginally increased survival (6.1 years versus 5.4 years; p =
      0.04). There were no difference in survival according to gender, parkinsonian, or
      pyramidal features or whether the patient was classified as striatonigral
      degeneration or olivopontocerebellar atrophy type. These results demonstrate the
      poor prognosis for patients with multiple system atrophy but may be biased toward
      the worst cases. Future research needs to recruit more representative samples.

PMID- 9040728
TI  - Longitudinal change in basal ganglia volume in patients with Huntington's
      disease.
AB  - Cross-sectional MRI studies demonstrating an association between caudate atrophy
      and symptom severity and duration of symptoms in patients with Huntington's
      disease (HD) have been assumed to reflect longitudinal changes in basal ganglia,
      but such neuropathologic progression has never been directly demonstrated.
      Subjects in the current study were 23 HD patients at various stages of the
      disorder who had two MRI images at least 10 months apart (mean interimage
      interval = 20.8 months). We measured volumes of caudate, putamen, and globus
      pallidus blind to the order of the images. For each structure, we calculated a
      change score by subtracting the volume obtained on the follow-up imaging from
      that obtained on the initial imaging. Results indicated significant decreases
      over time in caudate, putamen, and total basal ganglia volume. Age at onset and
      length of trinucleotide repeat correlated significantly with amount of volume
      change in caudate and total basal ganglia, even after controlling for length of
      interimage interval, duration of disease, and measures of symptom severity.
      Amount of change in basal ganglia structures was not significantly correlated
      with neurologic symptom severity at the time of the initial imaging or duration
      of symptoms. This is the first longitudinal MRI study to document progressive
      basal ganglia atrophy in HD, and suggests that quantitative neuroimaging with
      serial MRI may be useful in monitoring effectiveness of potential treatments. In
      addition, demonstration of greater rate of basal ganglia atrophy in patients with
      earlier symptom onset suggests that treatment effects may be more quickly
      observed in this subgroup of patients than in the general HD population.

PMID- 9040729
TI  - Neuroanatomy in Rett syndrome: cerebral cortex and posterior fossa.
AB  - Rett syndrome (RS), a neurodevelopmental disorder of unknown etiology occurring
      almost exclusively in females, is characterized by autistic-like behavior, motor
      dysfunction, loss of language skills, dementia, and microcephaly. This study is a
      follow-up and extension of a previously reported neuroimaging study of patients
      with RS. We replicated previously reported findings with a larger patient
      population, and the volumetric MRI analysis was extended to include an analysis
      of neuroanatomy of the posterior fossa. Twenty girls with RS were compared with
      individually age- and gender-matched normal controls. Patients with RS showed
      global reduction in gray- and white-matter volumes. The prefrontal, posterior
      frontal, and anterior-temporal regions showed the largest bilateral decrease in
      gray-matter volume, whereas white-matter volume was uniformly reduced throughout
      the brain. We found confirmation for the preferential reduction in caudate
      nucleus volume. However, we observed no preferential reduction in midbrain volume
      despite a preferential reduction in the midsagittal area of this region. We also
      present an individual case comparison between monozygotic twins discordant for
      RS.

PMID- 9040730
TI  - The neurologic complications of B-cell chronic lymphocytic leukemia.
AB  - We performed a retrospective study to characterize the type, frequency, and
      timing of neurologic complications in patients with B-cell chronic lymphocytic
      leukemia (B-CLL). We reviewed 962 total charts with a median follow-up time of
      57.5 months. There were 109 cases (11.3%) of neurologic complications, including
      69 cases (7.2%) of herpes zoster infection, 17 cases (1.8%) of other
      opportunistic infection, 14 cases (1.5%) of treatment-related conditions, eight
      cases (0.8%) of direct leukemic involvement of neural tissue, and 1 case (0.1%)
      of intracranial hemorrhage. No cases of a non-zoster opportunistic infection
      presented in early-stage (Rai stage 0-2) B-CLL, and only one case of direct
      leukemic involvement of neural structures presented in early-stage B-CLL. Of the
      25 cases of non-zoster or treatment-related complications, only 5 presented
      before 6 years from the initial B-CLL diagnosis. Three of these were in advanced
      stage B-CLL, staging could not be determined in one, and one presented in early
      stage B-CLL. We conclude that the overall neurologic complication rate of B-CLL
      is low, and that the Rai stage of the disease correlates best with the risk of
      developing neurologic complications. The occurrence of a related non-zoster
      neurologic complication in a patient with B-CLL stage 0-2 approaches 1:1,000.

PMID- 9040731
TI  - Craniectomy: an aggressive treatment approach in severe encephalitis.
AB  - BACKGROUND AND OBJECTIVE: Focal encephalitis may be associated with brain edema,
      which is often fatal. The control of intracranial pressure (ICP) is therefore
      crucial for further therapeutic strategies in space-occupying edema following
      encephalitis. However, aggressive treatment strategies such as hemicraniectomy
      have not been described in a larger series of patients. PATIENTS AND METHODS: We
      describe the clinical course and outcome in six patients who developed severe
      brain edema associated with acute encephalitis. All received maximum medical
      treatment for elevated ICP, but with signs of brainstem compression emerging,
      hemicraniectomy was performed to control ICP. RESULTS: All patients had a very
      severe encephalitic syndrome and were treated over the course of weeks in the
      neurocritical care unit (NCCU). However, all patients recovered almost completely
      and showed only mild or no neurologic deficit when reexamined after 4 months to 3
      years. CONCLUSIONS: Hemicraniectomy should be considered in patients with severe
      brain edema following encephalitis as a potentially lifesaving therapeutic
      measure. Moreover, the initial neurologic deficit seems to have no impact on the
      long-term clinical outcome.

PMID- 9040732
TI  - Chronic encephalitis and epilepsy in adults and adolescents: a variant of
      Rasmussen's syndrome?
AB  - Chronic encephalitis and epilepsy (Rasmussen's encephalitis) is a rare
      progressive disorder of uncertain etiology that usually occurs in children,
      producing focal epilepsy, hemiparesis, and intellectual deterioration. We
      identified 13 patients in whom seizures developed in adolescence or adulthood
      with a pathologic picture of chronic encephalitis. The clinical characteristics
      were more variable than those occurring in children, with the patients falling
      into three groups: five patients developed seizures in adulthood, but otherwise
      showed many resemblances to the childhood form; five developed seizures in
      adolescence, with similar presentation but rather more benign course than in the
      younger patients; and three presented with clinical features initially suggestive
      of a tumor. Occipital onset to the seizures appeared to be more common than in
      the childhood form, and bilateral disease also occurred.

PMID- 9040733
TI  - Adult-onset temporal lobe epilepsy associated with smoldering herpes simplex 2
      infection.
AB  - A 40-year-old man with chronic genital herpes simplex infection developed partial
      complex temporal lobe seizures of insidious onset, with EEG and MRI evidence of a
      unilateral temporal lobe destructive, atrophic process. Extensive workup did not
      reveal an infectious etiology. Three years of escalating number and severity of
      daily seizures with memory loss led to temporal lobectomy. Histologic study
      revealed active, low-level viral infection in the resected hippocampus and
      temporal lobe cortex, with immunohistochemical evidence for infection by herpes
      simplex 2, principally in neurons. In situ hybridization confirmed the presence
      of herpes simplex virus in neurons. Anticonvulsant-resistant seizure episodes
      began to recur several times daily soon after surgery, but the addition of
      acyclovir to the treatment regimen resulted in a substantial reduction in seizure
      occurrence, maintained for the subsequent 2.5 years.

PMID- 9040734
TI  - The course of benign partial epilepsy of childhood with centrotemporal spikes: a
      meta-analysis.
AB  - We performed a meta-analysis of studies on benign epilepsy of childhood with
      centrotemporal spikes (BECT) to ascertain whether clinical characteristics and
      outcome can be stated unequivocally. Using the Index Medicus and Medline CD+, we
      identified 525 publications. After applying the criteria of the International
      League against Epilepsy (ILAE) for BECT, 32 publications on 2,561 patients
      remained. After correction for inclusion bias and multiple publications on the
      same patient groups, 13 cohorts, comprising a total of 794 patients, were
      included. The aggregate proportional remission was 0.977; hence, no factors
      influencing outcome could be identified. Age at onset ranged from 3 months to 14
      years, age at last seizure ranged from 3 to 18 years. A Kurtzke survival analysis
      of proportions of children in remission by age was performed; at an older age,
      the proportion of patients in remission was 0.9997. Publications had highly
      heterogeneous methodologies and population characteristics; we conclude that
      current knowledge on BECT has been determined mainly by retrospective studies of
      biased cohorts, and that the uniformity per se of BECT as an epileptic syndrome
      may be, at least in part, a result of selection bias. We conclude that early
      prediction of seizure outcome in a new patient with BECT can not be given with
      certainty. Prospective, population-based studies are needed to delineate the
      clinical and EEG characteristics of this syndrome.

PMID- 9040735
TI  - Surgical treatment of patients with single and dual pathology: relevance of
      lesion and of hippocampal atrophy to seizure outcome.
AB  - Modern neuroimaging can disclose epileptogenic lesions in many patients with
      partial epilepsy and, at times, display the coexistence of hippocampal atrophy in
      addition to an extrahippocampal lesion (dual pathology). We studied the
      postoperative seizure outcome of 64 patients with lesional epilepsy (median
      follow-up, 30 months) and considered separately the surgical results in the 51
      patients with a single lesion and in the 13 who had dual pathology. In patients
      with a single lesion, 85% were seizure free or significantly improved (Engel's
      class I-II) when the lesion was totally removed compared with only 40% when there
      was incomplete resection (p < 0.007). All three patients with dual pathology who
      had both the lesion and the atrophic hippocampus removed became seizure free. In
      contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed
      at the lesion or at the hippocampus alone became seizure free (p < 0.05),
      although 4 of them showed significant improvement (Engel's class II). We conclude
      that the outcome in patients with single epileptogenic lesions is usually
      dependent upon the completeness of lesion resection. In patients with dual
      pathology, surgery should, if possible, include resection of both the lesion and
      the atrophic hippocampus.

PMID- 9040736
TI  - Underexpression of messenger RNA for peripheral myelin protein 22 in hereditary
      neuropathy with liability to pressure palsies.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is associated
      with a deletion in chromosome 17p11.2, including the gene for the peripheral
      myelin protein 22 (PMP-22). Because of the proposal that a decreased dosage of
      the PMP-22 gene was the cause of HNPP, we evaluated sural nerves from eight
      patients with the 17p11.2 deletion and from five normal controls. The relative
      amount of PMP-22 mRNA was significantly lower in HNPP patients compared with
      normal controls (p < 0.02) using a semiquantitative reverse transcriptase
      polymerase chain reaction. There was no significant decrease of Pzero mRNA. Sural
      nerves from HNPP patients showed normal immunostaining with monoclonal antibodies
      against PMP-22, Pzero, and myelin basic protein, and only rare myelinated fibers,
      classified as "tomacula," showed a patchy staining of the compact myelin with
      monoclonal antibody against PMP-22. The significant underexpression of PMP-22
      mRNA in HNPP patients compared with normal controls demonstrates that a decreased
      dosage of the PMP-22 gene is the most likely pathogenetic mechanism in HNPP.

PMID- 9040737
TI  - A novel frameshift mutation in PMP22 accounts for hereditary neuropathy with
      liability to pressure palsies.
AB  - Peripheral myelin protein PMP22 deficiency is associated with hereditary
      neuropathy with liability to pressure palsies (HNPP). Most HNPP cases are caused
      by a 1.5-megabase deletion in chromosome 17p11.2-12, a region that contains the
      PMP22 gene, whereas point mutations leading to HNPP are extremely rare. We have
      identified a family with clinical and electrophysiologic features of HNPP,in
      which all affected members are heterozygous carriers of a single base insertion
      in codon 94. This mutation is predicted to alter the reading frame and to result
      in a delayed termination signal. We conclude that the functional consequences of
      the frameshift are equivalent to those of the PMP22 deletion allele.

PMID- 9040738
TI  - Two large Spanish pedigrees with nonsyndromic sensorineural deafness and the
      mtDNA mutation at nt 1555 in the 12s rRNA gene: evidence of heteroplasmy.
AB  - We describe two unrelated Spanish families with isolated sensorineural hearing
      loss. In both pedigrees, the deafness was transmitted maternally, which suggested
      a mitochondrial, DNA (mtDNA) defect. Within the same pedigree, some relatives
      showed aminoglycoside-induced deafness, whereas others were not exposed to
      aminoglycosides before the onset of hearing loss. Molecular genetic analysis in
      both families showed the A-to-G transition at nt 1555 (A1555G) in the
      mitochondrial 12S rRNA gene. In one pedigree, the mutation was homoplasmic; in
      the other, it was heteroplasmic. To assess the frequency of this mutation, we
      screened 42 patients of various ethnic backgrounds with isolated sensorineural
      hearing loss; none harbored the A1555G mutation. This is the first report of
      heteroplasmy in a family with isolated sensorineural deafness associated with the
      A1555G mutation.

PMID- 9040739
TI  - Dose-dependent, central effects of botulinum neurotoxin type A: a pilot study in
      the alert behaving cat.
AB  - We investigated, in alert behaving cats, the long-term effects of botulinum
      neurotoxin (BoNT) type A injected into the lateral rectus muscle of the eye. We
      studied orthodromic field potentials recorded in the injected muscle, eye
      movements, and the discharge characteristics of the innervating abducens
      motoneurons. Single BoNT injections at doses from 0.01 to 0.3 ng/kg reduced, or
      even completely eliminated, eye movements in the abducting direction for up to 2
      months without affecting the motoneuron discharge profile that remained related
      to actual eye movements of the contralateral unparalyzed eye. This result
      indicates that abducens motoneurons were still under the influence of the ocular
      motor central control system regardless of their ineffective action on lateral
      rectus muscle fibers. We also conclude that paralysis per se is not enough to
      initiate axotomy-like neural responses in ocular motoneurons. The injection of
      BoNT at a dose of 3 ng/kg produced significant changes in the discharge pattern
      of abducens motoneurons lasting up to 3 months-the maximum time checked. This
      finding was probably due to retrograde and, perhaps, transneuronal effects of
      BoNT when injected in a high dose. The results give some indications of the
      maximum allowable dose that can be used without the induction of unwanted side
      effects in the motoneuronal pool innervating the injected muscle.

PMID- 9040740
TI  - Indictment of the microglia as the villain in multiple sclerosis.

PMID- 9040741
TI  - Hughlings Jackson's deductive science of the nervous system: a product of his
      thought collective and formative years.
AB  - This paper examines the life and work of John Hughlings Jackson (1835-1911), with
      particular attention to his early years in London, the "thought collective" into
      which he was initiated, and the consequent social ties, professional interests,
      hospital affiliations, scientific pursuits, aims, and ambitions that defined his
      medical career spanning almost half a century. There exists an abundant body of
      literature on Jackson, although it is far less extensive and substantive than his
      own writings (about 350 in number) in understanding his position and attitude
      concerning the study of diseases of the nervous system. This elucidation of the
      nature Jackson's pursuits throughout his career draws upon primary sources of
      information-the elaborate writings of Jackson himself and of his Victorian
      mentors and confreres. The latter constituted Jackson's thought collective, who
      contributed to a unique and previously undescribed document: Testimonials of Dr.
      J. Hughlings Jackson, M.D. (London, 1863). These medical men also contributed to
      the Medical Times and Gazette and belonged to the London Pathological Society and
      the New Sydenham Society. Jackson's thought collective and their shared beliefs
      and pursuits were instrumental in shaping Jackson's career as reflected by his
      later works. Jackson's professional pursuits and extensive writings marked a
      lifetime dedicated to developing a "Science of the Nervous System" according to a
      Millian-Spencerian form of deductive reasoning, to ultimately establish a
      rational basis for the treatment of nervous disease. Jackson and his
      contemporaries initiated and developed a deductive ideology and methodology that
      continue to be widely employed by neurologists today, and thus form the basis of
      the current neurological paradigm.

PMID- 9040742
TI  - Machado-Joseph disease in four Chinese pedigrees: molecular analysis of 15
      patients including two juvenile cases and clinical correlations.
AB  - Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder
      associated with the expansion of a (CAG)n array in the MJD1 gene. We analyzed the
      sizes of the (CAG)n array using DNA samples from 61 members of four Chinese MJD
      families and 18 Chinese normal control subjects and confirmed that the (CAG)n
      array in 15 MJD chromosomes was expanded to 72-86 repeat units. There were no
      subjects with (CAG)n array sizes intermediate between those of normal and MJD
      affected groups. Meanwhile, we found a significant negative correlation between
      the age of onset of symptoms and (CAG)n array size. The largest (CAG)n array of
      86 repeat units was in the youngest patient, whose age of onset was 5 years. The
      intergenerational increase in number of CAG repeat units was associated with the
      clinical phenomenon of anticipation.

PMID- 9040743
TI  - Dystrophin expression in a Duchenne muscular dystrophy patient with a frame shift
      deletion.
AB  - The exon 45 deletion is a common dystrophin gene deletion. Although this is an
      out-of-frame deletion, which should not allow for protein synthesis, it has been
      observed in mildly affected patients. We describe a patient with an exon 45
      deletion who produced protein, but still had a severe Duchenne muscular dystrophy
      phenotype. RT-PCR analysis and cDNA sequencing from the muscle biopsy sample
      revealed that the exon 45 deletion induced exon skipping of exon 44, which
      resulted in an in-frame deletion and the production of dystrophin. A
      conformational change in dystrophin induced by the deletion is proposed as being
      responsible for the severe phenotype in the patient. We feel that the variable
      clinical phenotype observed in patients with the exon 45 deletion is not due to
      exon splicing but may be the result of other environmental or genetic factors, or
      both.

PMID- 9040744
TI  - A novel point mutation in the peripheral myelin protein 22 (PMP22) gene
      associated with Charcot-Marie-Tooth disease type 1A.
AB  - We studied the peripheral myelin protein gene PMP-22 in a large Sardinian family
      with Charcot-Marie-Tooth disease type 1A (CMT1A), in which the duplication
      commonly found in CMT1A was absent, but with evidence of linkage on chromosome
      17. Sequencing of DNA and cDNA showed a missense point mutation G368-->T in exon
      5 of PMP22, predicted to determine a valine for glycine substitution at codon
      107, which could be plotted in the center of the PMP22 protein putative
      transmembrane domain III. Using sequence-specific oligonucleotide probes (SSOP),
      we found the point mutation in all affected CMT1A subjects but not in healthy
      family members or in 314 chromosomes of controls, thus indicating that the G368-
      >T point mutation is not a polymorphism. In the hypothetical model of PMP22, the
      amino acid at position 107 plots deeply into alpha-helical transmembrane domain
      III, a domain where point mutations have never previously been found. Although
      the same mutation was present in all CMT1A subjects examined, clinical findings
      showed a different stereotyped pattern in relation to the generation examined,
      for a progressive increase in severity and an earlier onset from the first to the
      third generation examined. Molecular analysis suggests that CMT1A disease in this
      family is due to the G368-->T point mutation, although other mechanisms may
      account for the clinical variability in the members of different generations.

PMID- 9040745
TI  - Autoantibodies to glutamate receptor subunit GluR2 in nonfamilial
      olivopontocerebellar degeneration.
AB  - We describe a 63-year-old man with a 5-year history of progressive sporadic
      olivopontocerebellar atrophy (OPCA) who exhibits high serum titers of IgM
      autoantibodies to the neuronal glutamate receptor subunit GluR2.
      Immunohistochemistry revealed intense staining of mouse cerebellar Purkinje cells
      and cells in the pontine nuclei and olivary complex. Glutamate receptor currents
      were activated in a subset of cultured mouse neurons by an anti-GluR2 IgM
      fraction, and they were blocked by the competitive AMPA-type glutamate receptor
      antagonist CNQX and by a synthetic peptide to a specific epitope region of GluR2
      (AA 369-393). The patient was treated with nine courses of plasmapheresis with
      little improvement of symptomatology. However, IgM titers to GluR2 decreased
      approximately 8-fold and the serum functional activity decreased proportionally.
      These findings may suggest a role for autoimmunity to glutamate receptors in the
      pathophysiology of certain forms of progressive nervous system degeneration.

PMID- 9040746
TI  - Intradermal recombinant human nerve growth factor induces pressure allodynia and
      lowered heat-pain threshold in humans.
AB  - Nerve growth factor (NGF) plays a biologic role in the development and
      maintenance of sympathetic and small sensory neurons. Because it facilitates
      nerve fiber regeneration, lowers heat-pain threshold (hyperalgesia), and prevents
      or improves nerve dysfunction in experimental neuropathy, it is being considered
      as a putative treatment for certain human polyneuropathies. In 16 healthy
      subjects, we tested whether intradermal injection of minute doses of recombinant
      human NGF (1 or 3 micrograms) compared with saline induces hyperalgesia or alters
      cutaneous sensation (at the site of injection) as measured by symptom scores,
      clinical examination, or quantitative sensory testing with Computer Assisted
      Sensory Examination (CASE IV). Most subjects had, as their only symptom,
      localized tenderness of the NGF-injected site and only when the site was bumped
      or compressed. Slight discomfort developed in volar wrist structures (with
      flexion of fingers) or tenderness of deep structures to palpation over the
      bicipital groove or supraclavicular region. The Neuropathy Symptoms and Change
      questionnaire indicated that pressure allodynia was significantly localized to
      the NGF-injected side from 3 hours to 21 days after injections. Light stroking of
      the skin did not induce tactile allodynia. Compression of injected sites induced
      pressure allodynia that occurred more frequently and significantly on the NGF
      injected side after 3 hours and was maintained for several weeks. No abnormality
      of vibratory or cooling detection threshold developed from NGF injection. By
      contrast, heat-pain threshold (HP 0.5, p = 0.003) and an intermediate level of
      heat-pain (HP 5.0, p < 0.001) were significantly lowered 1, 3, and 7 days (and in
      some cases at 3 hours and 14 and 21 days) after NGF injection. The time course of
      pressure allodynia and heat-pain hyperalgesia is too rapid to be explained by
      uptake of NGF by nociception terminals, retrograde transport, and upregulation of
      pain modulators. Local tissue mechanisms appear to be implicated. It remains to
      be tested whether recombinant human NGF prevents, stabilizes, or ameliorates
      small fiber human neuropathies.

PMID- 9040747
TI  - Torsional eye movements in patients with skew deviation and spasmodic
      torticollis: responses to static and dynamic head roll.
AB  - We measured torsional eye movements induced by sinusoidal rotation or static
      tilt, of the head in roll while viewing a far or near target in 4 patients with
      skew deviation due to brainstem lesions, 4 patients with spasmodic torticollis
      (ST), 2 patients with unilateral eighth nerve section (VIIIS), and 10 normal
      subjects. Torsional nystagmus was present in all 4 patients with skew deviation.
      In subjects and patients, responses to both sinusoidal and static roll were
      larger while viewing the far target, consistent with factors dictated by
      geometry. Response gains to sinusoidal roll were abnormal in 3 patients with skew
      (increased in one, decreased in two), abnormal in 3 with ST (increased in 1,
      decreased in 2), and in abnormal both VIIIS patients (decreased). Greater
      abnormalities were evident in 3 skew patients while rolling away from the side of
      their brainstem lesions and in both VIIIS patients while rolling toward their
      lesioned ears. There were similar but less pronounced changes during static head
      roll. We conclude that patients with skew, ST, and VIIIS may all have abnormal
      ocular counter-rolling that is more evident during dynamic testing while viewing
      a far target. Such abnormalities endure because of the limited influence exerted
      by vision on torsional eye movements.

PMID- 9040748
TI  - Apolipoprotein E-epsilon 2 and Alzheimer's disease: genotype influences
      pathologic phenotype.
AB  - To determine whether apolipoprotein E epsilon 2 (APOE-epsilon 2) affects
      neuropathology in aging and Alzheimer's disease (AD), we compared beta-amyloid
      plaque (A beta P) and neurofibrillary tangle densities, neuropil thread
      formation, and amyloid angiopathy in five APOE-epsilon 2/3 AD patients, five APOE
      epsilon 3/3 AD patients, five APOE-epsilon control patients, and five APOE
      epsilon 3/3 control patients. We examined the (frontal and parietal) neocortex,
      hippocampus, entorhinal cortex, and cerebellum and found A beta P densities to be
      lower (t = 3.121, p = 0.011) in the cortex of APOE-epsilon 2/3 AD patients than
      in APOE-epsilon 3/3 AD patients. Amyloid angiopathy was also less in APOE-epsilon
      2/3 patients than in APOE-3/3 patients (U = 4.500, p = 0.027). Control APOE
      epsilon 2/3 brains had little AD-related pathology; even our 102-year-old control
      case showed few A beta Ps compared with the elderly APOE-epsilon 3/3 cases. The
      APOE-epsilon 2/3 genotype may influence pathologic phenotype in some aged normal
      and AD populations.

PMID- 9040749
TI  - Subarachnoid hemorrhage in a patient with Lyme disease.
AB  - Neuroborreliosis can cause a wide variety of seemingly unrelated neurologic
      abnormalities. Although the epidemiology, etiology, and pathology of this
      infection have been well documented, the pathogenesis and diagnosis continue to
      be problematic. In the current study we report a case of Lyme disease in which
      subarachnoid hemorrhage was the presenting feature of a patient with
      polyradiculoneuropathy and encephalopathy. Magnetic resonance imaging of the
      spine demonstrated diffuse pial and meningeal enhancement with more focal nodular
      areas of involvement.

PMID- 9040750
TI  - Vascular lesions in Chinese patients with transient ischemic attacks.
AB  - We studied 96 Chinese patients with TIAs using transcranial Doppler and duplex
      ultrasonography. We found intracranial stenosis or occlusion in 51% of cases and
      extracranial disease in 19% of cases. The most common intracranial lesion was
      stenosis of the terminal internal carotid artery or proximal middle cerebral
      artery, whereas the most common extracranial lesion was stenosis of the carotid
      bifurcation.

PMID- 9040751
TI  - Long-term follow-up of patients with subacute sclerosing panencephalitis treated
      with intraventricular alpha-interferon.
AB  - We treated 22 patients with subacute sclerosing panencephalitis (SSPE) with
      intraventricular alpha-interferon (alpha-IFN) and oral inosiplex between 1986 and
      1991. The follow-up for 56 to 108 months demonstrates a higher survival rate in
      these patients compared with those who did not receive alpha-IFN. However, eight
      of 11 patients whose condition improved after alpha-IFN treatment and five of
      five patients whose condition stabilized after alpha-IFN experienced neurologic
      deterioration 6 to 90 months after treatment; three of 11 and four of five died.
      The use of inosiplex did not influence the prognosis. Re-administration of the
      same regimen was not effective in one patient. Treatment-induced remissions in
      SSPE can be temporary, analogous to spontaneous remissions. Longer treatment with
      higher doses, or combinations of drugs, may be required.

PMID- 9040752
TI  - Brainstem CMV encephalitis in AIDS: clinical case and MRI features.
AB  - We describe the clinical case and MRI findings of a patient with acquired immune
      deficiency syndrome and pathologically confirmed cytomegalovirus encephalitis.
      Prevalent brainstem and cerebellar signs together with almost exclusive
      involvement as seen on MRI of posterior fossa structures at the onset of the
      symptoms were the main features of our case.

PMID- 9040753
TI  - Sydenham Chorea: magnetic resonance imaging reveals permanent basal ganglia
      injury.
AB  - MRI of the brain of a 3-year-old boy performed 3 days after the onset of
      hemichorea (Sydenham Chorea) revealed abnormal signal and enlargement of the
      contralateral caudate and putamen. Follow-up imaging 40 months later showed a
      persistent cystic appearance of the caudate and putamen. This case is the first
      report of permanent MRI abnormalities after Sydenham Chorea.

PMID- 9040754
TI  - Magnetization transfer imaging in progressive multifocal leukoencephalopathy.
AB  - We report a patient with biopsy-proven progressive multifocal leukoencephalopathy
      (PML) who was serially imaged with MRI and magnetization transfer imaging. The
      magnetization transfer ratio (MTR) was profoundly and significantly diminished
      when compared with normal control subjects. The pattern of MTR was distinct from
      that of MS and periventricular ischemic white matter disease. Magnetization
      transfer imaging techniques may aid in the differential diagnosis of PML.

PMID- 9040755
TI  - How high is high in steroid treatment of Vogt-Koyanagi-Harada syndrome?

PMID- 9040756
TI  - Tremor caused by trimethoprim-sulfamethoxazole in a patient with AIDS.

PMID- 9040757
TI  - Spontaneous calcific cerebral embolus.

PMID- 9040758
TI  - Isolated bilateral masseter atrophy in X-linked recessive bulbospinal
      neuronopathy.

PMID- 9040759
TI  - Use of fluid attenuating inversion recovery, MR angiogram, and diffusion-weighted
      MRI techniques for assessment of pontine infarction in a patient treated with
      radiation therapy for pituitary neoplasm.

PMID- 9040760
TI  - Inheritance of three distinct muscle chloride channel gene (CLCN1) mutations in a
      single recessive myotonia congenita family.

PMID- 9040761
TI  - Multifocal motor neuropathy with conduction block after Campylobacter jejuni
      enteritis.

PMID- 9040762
TI  - Brain edema after carotid endarterectomy.

PMID- 9040763
TI  - VKH [corrected] syndrome.

PMID- 9040764
TI  - Early frontal impairment as a predictor of dementia in Parkinson's disease.

PMID- 9040765
TI  - Postoperative hyponatremia.

PMID- 9040766
TI  - Postoperative hyponatremia.

PMID- 9040767
TI  - Postoperative hyponatremia.

PMID- 9040768
TI  - Intracranial hypotension.

PMID- 9040769
TI  - Preclinical AD.

PMID- 9040770
TI  - Occipital arteriovenous malformations.

PMID- 9040771
TI  - Dropped head syndrome.

PMID- 9040772
TI  - Dropped head syndrome.

PMID- 9040773
TI  - Hereditary Alexander's disease.

PMID- 9040774
TI  - Associated blepharospasm in lower pontine lesions.

PMID- 9040775
TI  - Report of the Third International Workshop on Human Chromosome 8 Mapping. San
      Antonio, Texas, October 25-27, 1996.

PMID- 9040776
TI  - Report and abstracts of the Third International Workshop on Human Chromosome 13
      Mapping. Tarrytown, New York, October 29-31, 1995.

PMID- 9040777
TI  - Report of the Fourth International Workshop on Human Chromosome 18 Mapping.
      Boston, Massachusetts, October 7-9, 1996.

PMID- 9040778
TI  - Human CLAPS2 encoding AP17, a small chain of the clathrin-associated protein
      complex: cDNA cloning and chromosomal assignment to 19q13.2-->q13.3.
AB  - We have cloned the cDNA for the human homolog of the rat AP17 gene, a small chain
      of the clathrin-associated protein complex AP-2. The cDNA is highly conserved
      between rat and human. Human AP17, gene symbol CLAPS2 (clathrin
      associated/assembly/adaptor protein, small 3, 17 kDa), was assigned to chromosome
      region 19q13.2-->q13.3.

PMID- 9040779
TI  - Chromosome mapping of rat histone genes H1fv, H1d, H1t, Th2a and Th2b.
AB  - Chromosome assignment of the rat histone genes H1t, H1d (H1.4), H1fv (H10), Th2a
      and Th2b is described. The testicularly expressed histone genes H1t, Th2a and
      Th2b could be assigned to rat chromosome (RNO) 17 by PCR analysis of somatic cell
      hybrid DNAs. The H1d gene was mapped to RNO17p12-->p11 by FISH. These genes might
      form a histone gene cluster homologous to that found on HSA6p21.3 in humans and
      MMU13A2-3 in mice. The rat histone H1fv gene was assigned to RNO7 by PCR. This
      result allows the inclusion of rat H1fv to an established conserved group of
      syntenic genes in rat, mouse and human on chromosomes RNO7, MMU15 and HSA22,
      respectively.

PMID- 9040780
TI  - Characterization and mapping of the Xiphophorus maculatus (Teleostei:
      Poeciliidae) RPS15 gene.
AB  - We have determined the nucleotide sequence and gene map location of the
      Xiphophorus maculatus homologue of RPS15 (ribosomal protein S15, alias RIG). The
      Xiphophorus RPS15 cDNA encodes 145 amino acids, which show 94% identity compared
      to deduced mammalian and avian RPS15 amino acid sequences. At the nucleotide
      level, 84% sequence identity is maintained between the fish and human gene, while
      homologous amphibian and avian sequences show about 80% nucleotide identity
      compared to the Xiphophorus sequence. Nucleotide identity substantially decreases
      when the fish gene is compared to Arabidopsis S15 (64%) and yeast S21 (55%)
      genes. Genetic linkage analysis of an RPS15 restriction fragment length
      polymorphism in backcross hybrids generated from the cross X. helleri x (X.
      maculatus Jp 163 B x X. helleri) demonstrated linkage of Xiphophorus RPS15 to the
      EGFR, UMPK and YES loci in Xiphophorus Linkage Group VI.

PMID- 9040781
TI  - Sex chromosome linkage of 5S rDNA in rainbow trout (Oncorhynchus mykiss).
AB  - The karyotype of the rainbow trout is characterized by a primitive XX/XY sex
      determining chromosomal system. (Thorgaard et al., 1977). In the present study
      using FISH we have physically linked the 5S rRNA genes to the partially
      undifferentiated X chromosome pair. PCR amplified 5S rDNA was used for FISH and
      hybridization signals indicated that the genes were duplicated, present in one
      acrocentric and one metacentric pair of chromosomes. After analyzing several
      individuals, the female metaphases showed four fluorescent signals whereas males
      presented only three signals. Two of the three signals obtained in males
      corresponded to the metacentric pair whereas the single signal was mapped to the
      heterochromatin that cytologically differentiates the X chromosome from the Y
      chromosome. Double FISH experiments demonstrated that the 5S rDNA which is not
      sex linked is located at the NOR bearing arm close to the major ribosomal RNA
      genes (5.8S, 18S and 28S), similar to the situation observed in Atlantic salmon
      (Pendas et al., 1994a).

PMID- 9040782
TI  - In vivo cytogenetic damage revealed by FISH analysis of micronuclei in uncultured
      human T lymphocytes.
AB  - FISH analysis of micronuclei in uncultured human T lymphocytes provides a
      convenient new possibility to assess structural and numerical chromosome damage
      in vivo. In women. T-cell micronuclei mostly contained whole chromosomes (71.6%),
      especially the X chromosome (28.5%). Cell culture (72 h) enhanced the frequency
      of micronuclei harboring acentric fragments 2.9 fold and the X chromosome 1.5
      fold. X-chromosome-positive micronuclei were particularly prevalent (42.0%) in
      binucleate cells produced by cytochalasin B, a cytokinesis inhibitor used to
      identify cells that have divided in vitro. This was explained by a decrease in
      autosome-containing and an increase in X-positive micronuclei.

PMID- 9040783
TI  - The Ag-NOR proteins present a crescent-shaped distribution at the secondary
      constrictions of metaphase PtK1 chromosomes.
AB  - The ultrastructural distribution of the proteins responsible for the silver
      staining of NORs was analyzed on serial thin sections of preembedded silver
      stained rat kangaroo PtK1 metaphase chromosomes. Our results show that the Ag-NOR
      proteins present a crescent-shaped distribution at the secondary constriction of
      each chromatid. Moreover, in some cases the crescent-shaped structures of both
      chromatids are not symmetrically arranged but show different orientations. These
      observations, together with our own and previously reported light microscopy
      results obtained on silver-stained mammalian chromosomes, lead us to suggest a
      mechanism for the formation of apparent secondary constrictions at NORs.

PMID- 9040784
TI  - Spontaneous and aphidicolin-sensitive fragile site 3cen co-localizes with the
      (TTAGGG)n telomeric sequence in Chinese hamster cells.
AB  - Aphidicolin-sensitive fragile sites were analyzed in immortalized Chinese hamster
      embryonal fibroblast cells (CHEF18) at three different passages along their
      spontaneous progression toward tumorigenicity. Five fragile sites (viz., 12q22,
      3cen, 3p21, 3q31, and Xq21) were detected. Three of these sites carry spontaneous
      aberrations and are thus regions of chromosomal instability; however, they were
      not involved in the formation of the clonal rearrangements that are
      characteristic of CHEF 18 cells. The presence of the (TTAGGG)n telomeric sequence
      in chromosome bands associated with fragile sites was investigated using
      fluorescence in situ hybridization and primed in situ labeling. A common location
      of fragile sites and telomeric sequence was found at the centromere of chromosome
      3.

PMID- 9040785
TI  - Allelic fusion of DNA topoisomerase II alpha and retinoic acid receptor alpha
      genes in adriamycin-resistant p388 murine leukemia revealed by fluorescence in
      situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) analysis of metaphase and decondensed
      free chromatin fibers from Adriamycin (ADR)-sensitive and ADR-resistant murine
      cells demonstrated a close juxtaposition of topoisomerase II alpha (Top2a) and
      retinoic acid receptor alpha (Rara) genes in adjacent chromatin in the drug
      resistant cells, and a close but separate genetic proximity in normal murine
      chromatin. This provides physical evidence that the chromosome 11 allelic
      rearrangement resulting in a chimeric truncated Top2a/Rara transcript in the ADR
      resistant cells is due to a novel fusion of the Topo2a and Rara genes. This is
      the first description of a Rara gene disruption in cells selected for
      antineoplastic drug resistance.

PMID- 9040786
TI  - Application of micro-FISH to delineate deletions.
AB  - Microdissection combined with fluorescence in situ hybridization (micro-FISH) was
      used to visualize deletions in rearranged human chromosomes and in a de novo
      translocation. In each experiment five copies of a structurally aberrant
      chromosome or of the two chromosomes involved in the de novo translocation were
      isolated by microdissection and amplified using DOP-PCR. The PCR products were
      then used as probes for FISH to metaphase chromosomes of three patients. After
      reverse chromosome painting, the structurally aberrant chromosomes were
      completely painted, and the region deleted in the aberrant chromosomes was
      visible in the normal chromosomes. The smallest deletion that could be
      demonstrated this way was a microdeletion of approximately 6 x 10(6) bp, which is
      frequently reported in Angelman and Prader-Willi syndromes.

PMID- 9040787
TI  - Complementary replication R- and G-band patterns induced by cell blocking at the
      R-band/G-band transition, a possible regulatory checkpoint within the S phase of
      the cell cycle.
AB  - The characteristic band patterns of replication banding (dynamic banding) were
      analyzed. High-resolution (550-1,250 bands per haploid genome) G- and R-band
      patterns were obtained after 5-bromo-2'-deoxyuridine (BrdU) incorporation during
      early or late S phase. Thymidine-BrdU permutation culture methods, which arrest
      DNA synthesis at the R-band/G-band transition, allow complementary BrdU
      substitution. The RBI (R bands by BrdU using immunological staining) and GBI (G
      bands by BrdU using immunological staining) band patterns were complementary for
      all chromosomes. There was no overlapping, and every part of each chromosome was
      positively stained by one of the two banding procedures. Comparative analysis of
      RBG (R bands by BrdU using Giemsa staining) and RBI band patterns, as well as GBG
      (G bands by BrdU using Giemsa staining) and GBI band patterns, showed good
      congruency, displaying a very good band-for-band match. The congruency and
      complementarity found for these band patterns show that high concentrations of
      both thymidine and BrdU blocked S-phase progression near the R-band to G-band
      replication transition within the S phase. They also prove that BrdU
      incorporation is complementary and, therefore, demonstrate the existence of the
      R/G transition: a possible regulatory checkpoint within the S phase of the cell
      cycle.

PMID- 9040788
TI  - Mapping of 29 YAC clones and identification of 3 YACs spanning the translocation
      t(3;8)(p14.2;q24.1) breakpoint at 8q24.1 in hereditary renal cell carcinoma.
AB  - The constitutional balanced translocation (3;8)(p14.2:q24.1) has been described
      in a family in which a arge number of individuals developed renal cell carcinoma
      RCC) at an early age. The translocation event in which genes from the 3p14.2 and
      the 8q24.1 sites are brought in close proximity is considered a critical, initial
      step for the development and progression of RCC. Even though the 3p14.2
      breakpoint region has been cloned, a gene has not yet been identified, which may
      be responsible for either the initiation or progression of hereditary RCC. As a
      crucial step toward cloning the 3;8 breakpoint at the 8q24.1 site, we have mapped
      a series of YACs which surround this region by fluorescence in situ hybridization
      (FISH). Three YACs have been identified that span the 8q24.1 breakpoint region.
      One of these YACs is approximately 180 kb in length, and has been used to
      initiate construction of a high resolution cosmid contig. Several cosmids have
      been isolated which have been positioned in relation to the 8q24.1 breakpoint
      region. In addition, we have positioned 26 other YACs in relation to the 3;8
      translocation breakpoint. These results provide a basis for the isolation of
      genes surrounding 3;8 RCC translocation breakpoint region at 8q24.1.

PMID- 9040789
TI  - Genomic localization of the human gene encoding Dr1, a negative modulator of
      transcription of class II and class III genes.
AB  - Dr1 is a nuclear protein of 19 kDa that exists in the nucleoplasm as a
      homotetramer. By binding to TBP (the DNA-binding subunit of TFIID, and also a
      subunit of SL1 and TFIIIB), the protein blocks class II and class III
      preinitiation complex assembly, thus repressing the activity of the corresponding
      promoters. Since transcription of class I genes is unaffected by Dr1. it has been
      proposed that the protein may coordinate the expression of class I, class II and
      class III genes. By somatic cell genetics and fluorescence in situ hybridization,
      we have localized the gene (DR1), present in the genome of higher eukaryotes as a
      single copy, to human chromosome region 1p21-->p13. The nucleotide sequence
      conservation of the coding segment of the gene, as determined by Noah's ark blot
      analysis, and its ubiquitous transcription suggest that Dr1 has an important
      biological role, which could be related to the negative control of cell
      proliferation.

PMID- 9040790
TI  - Isolation of 45 exon-like fragments from 8p22-->p21.3, a region that is commonly
      deleted in hepatocellular, colorectal, and non-small cell lung carcinomas.
AB  - The loss of heterozygosity that is frequently observed at chromosome 8p22-->p21.3
      in hepatocellular carcinomas (HCC), colorectal cancers (CRC), prostate cancers
      (PRC). and non-small cell lung cancers (NSCLC), suggests the presence there of
      one or more tumor suppressor genes associated with development and/or progression
      of these types of carcinomas. We have constructed a cosmid contig map of the
      target region by means of Southern hybridization and have isolated 45 exon-like
      fragments by exon amplification, using cosmid clones derived from three yeast
      artificial chromosomes (YACs). The map and the exon-like fragments reported here
      will be useful resources for isolation of the putative tumor suppressor gene(s)
      as well as other novel genes located in the 8p22-->p21.3 region.

PMID- 9040791
TI  - Molecular analysis of the genomic structure of the human Y chromosome in the
      euchromatic part of its long arm (Yq11).
AB  - Conventional methods of long range restriction mapping for analysis of the
      genomic DNA structure failed in Yq11, because single-copy DNA probes for blot
      hybridization analyses are rare and the rate of DNA methylation is high in this Y
      region. Numerous repetitive sequence blocks of unknown extensions are scattered
      throughout Yq11 and a patchwork of X-Y homologous DNA blocks were found by
      different investigators. Therefore, our approach towards a molecular analysis of
      this Y region reduced this complexity by performing first its molecular analysis
      in YAC clones mapping to Yq11. YACs contain only a part of the whole Yq11 DNA
      structure. In this paper, we present our first results of this approach based on
      quantitative blot analysis of 51 DNA loci in 67 YAC clones. The YACs were
      isolated from the three CEPH libraries and mapped to a contig of 13 Mb from
      proximal to distal Yq11 with aid of a detailed interval map. In distal Yq11, our
      analysis revealed the presence of local amplification events of different DNA
      domains. A model of their possible arrangement is presented.

PMID- 9040792
TI  - Practice guidelines and the National Comprehensive Cancer Network.

PMID- 9040793
TI  - Molecular study of sex steroid receptor gene expression in human colon and in
      colorectal carcinomas.
AB  - BACKGROUND: Sex steroid hormones influence function of the human gastrointestinal
      tract. Although the specific receptor proteins have been identified in surgical
      specimens of both intestinal mucosa and colorectal carcinomas, it is still
      unknown whether they are expressed in intestinal epithelial cells. METHODS:
      Expression of androgen receptor (AR) protein and estrogen receptor (ER) protein
      was studied by Scatchard analysis and ELISA (for ER only) in surgical specimens
      of normal-appearing mucosa, colorectal carcinomas, isolated colonocytes, and
      human colorectal carcinoma cell lines. Northern analysis was applied to identify
      the appropriate mRNAs, followed by the sensitive technique of reverse
      transcription-polymerase-chain-reaction (RT-PCR). RESULTS: AR protein was
      identified in all surgical specimens analyzed and ER protein in 10 out of 13
      normal-appearing mucosa specimens and 4 out of 7 colorectal carcinomas. The
      receptor proteins were not found in isolated colonocytes or in the transformed
      cell lines. RT-PCR confirmed that none of the isolated normal colonocytes or
      transformed colorectal carcinoma-derived cells expressed these mRNAs. Intestinal
      smooth muscle cells and fibroblasts were found to express sex steroid receptor
      mRNAs. CONCLUSIONS: Both receptors are present in human large intestine but are
      expressed in stromal cells and not in intestinal epithelial cells. We hypothesize
      that sex steroids may influence the function of colonocytes indirectly through
      stromal-epithelial interactions.

PMID- 9040794
TI  - Lymph node and perinodal tissue tumor involvement in patients with esophagectomy
      and three-field lymphadenectomy for carcinoma of the esophagus.
AB  - BACKGROUND: Lymph node metastasis is a definitive prognostic factor; however,
      perinodal fat tumor invasion has not been fully elucidated. METHODS:
      Periesophageal nodes and the surrounding fibrofatty tissue obtained from 131
      patients who underwent esophagectomy were examined. RESULTS: Of 9,789 nodes
      removed, 645 (6.6%) demonstrated invasion and 143 (1.5%) showed perinodal
      involvement. Of 131 patients 97 (74.0%) had lymph node involvement and 43 (32.8%)
      had perinodal fat involvement. The incidence of perinodal tissue involvement
      correlated significantly with the number of nodes involved; 23 (42.6%) of 54
      patients with a total of 1-8 nodes involved and 19 (95.0%) of 20 patients with 9
      or more involved nodes had perinodal involvement. The 5-year survival for 33
      patients without involved nodes or perinodal tissue extension was 59.7%, compared
      to 14.0% for 43 patients with perinodal fat involvement. CONCLUSION: Perinodal
      tissue carcinoma into the periesophageal fibrofatty tissue was a decisive
      prognostic factor in patients with curative resection for esophageal carcinoma.

PMID- 9040795
TI  - Adjuvant immunotherapy in melanoma with irradiated autologous tumor cells and low
      dose cyclophosphamide.
AB  - BACKGROUND: Patients with metastatic melanoma to their regional lymph nodes have
      a poor prognosis despite lymphadenectomy. In an attempt to improve their
      survival, this feasibility study was undertaken. METHODS: Twenty-two melanoma
      patients, who presented with enlarged regional lymph nodes, underwent therapeutic
      lymphadenectomy. They were found to have N2 nodal disease, with no evidence of
      distant metastases, i.e., advanced Stage III disease. One month after the
      lymphadenectomy, each patient received five autologous tumor vaccines. Each
      vaccine consisted of 20 x 10(6) irradiated autologous tumor cells (20,000 cGy)
      injected intradermally. The first two vaccines contained BCG and were given 1
      week apart. The other three vaccines consisted of irradiated tumor cells only
      without BCG, administered over 2-, 4-, and 8- week intervals, respectively.
      Cyclophosphamide was administered intravenously as 300 mgm/m2 3 days prior to
      vaccines 1, 4, and 5 to reduce the population of T-suppressor cells. The patients
      were observed with no additional therapy. Three patients developed recurrences
      and these site were resected, and the patients were revaccinated in the same
      fashion utilizing the new tumor cells. RESULTS: After a follow-up of 4-6 years,
      15 patients (including 3 who were revaccinated) of the initial 22 patients
      (68.2%) are alive free of disease. CONCLUSIONS: Adjuvant immunotherapy with
      irradiated autologous melanoma cells and low dose cyclophosphamide seemed to
      yield better relapse-free survival than the historically reported 10-25%.

PMID- 9040796
TI  - Outcome of surgical resection for chest wall recurrence in breast cancer
      patients.
AB  - BACKGROUND: Although recurrent breast cancer is a systemic disease, there might
      be several exceptions where local treatment has a favorable outcome. METHODS:
      From 1989 to 1996, 15 patients underwent full thickness chest wall resection,
      supported by peri- and postoperative systemic treatments for patients with
      isolated chest wall recurrences, including soft tissue local recurrence and
      parasternal lymph node metastasis. RESULTS: The 5-year survival rate after
      surgical removal was 47%. Patients with > 5-year disease-free intervals (DFI)
      after mastectomy showed a long survival after chest wall resection. Local
      failures appeared in four cases whose surgical margins were positive. No serious
      complication except one pyothorax occurred after surgery. CONCLUSIONS: It is
      suggested that surgical treatment with a full thickness chest wall resection
      might have a favorable prognosis for selected patients with solitary lesion and
      long DFI.

PMID- 9040797
TI  - Seroma formation following axillary dissection for breast cancer: risk factors
      and lack of influence of bovine thrombin.
AB  - BACKGROUND: Seromas of the axillary space following breast surgery can lead to
      significant morbidity and delay in the initiation of adjuvant therapy. A
      prospective, randomized study was undertaken to evaluate the effect of bovine
      spray thrombin on seroma formation following either modified radical mastectomy
      (MRM) or lumpectomy with axillary dissection (LAD). In addition, risk factors for
      seroma formation were analyzed and identified. METHODS: A total of 101 patients
      were randomized to receive either bovine thrombin (20,000 units) (treatment
      group) or no thrombin (control group) applied to their axilla following either
      MRM or LAD. Drains were left in place until the preceding 24-hour drainage was <
      40 milliliters. The number of days the drains were in place and wound
      complications (including seroma formation) were recorded. RESULTS: Forty-nine (n
      = 49) patients were assigned to the treatment gorup and 52 (n = 52) to the
      control group. MRM was performed on 60 patients (59%) and LAD oN 41 (41%).
      Eighteen of the 49 patients (37%) in the thrombin group developed a seroma in
      comparison to 21 of the 52 control patients (40%) (P = 0.71). Significant risk
      factors for seroma formation included increased age, patient weight, initial 72
      hour wound drainage, and LAD. No statistically significant differences were
      observed between treatment and control groups with respect to time to drain
      removal, or the incidence of other wound complications. CONCLUSION: Although
      thrombin by itself appears to have no effect on subsequent seroma development
      following axillary dissection, the identification of predictive variables will be
      helpful in designing future trials aimed at reducing the incidence of this common
      complication of breast surgery.

PMID- 9040798
TI  - Comparison of the surgical results of lobectomy with bronchoplasty and
      pneumonectomy for lung cancer.
AB  - BACKGROUND: We retrospectively compared sleeve lobectomy (SL) and pneumonectomy
      (PN) for lung cancer in terms of surgical complications and postoperative disease
      free survival, as well as incidence and pattern of recurrent disease. METHODS:
      From 1977 to 1993. 29 patients with primary lung cancer underwent sleeve
      resection at our institution. The pneumonectomy group consisted of 29 cases that
      had been selected during the same period according to the following criteria: (1)
      in a tumor located in the upper lobe, there was no invasion within 1 cm from both
      the carina and the orifice of the middle and the lower lobe bronchus, whereas in
      a tumor located in the middle or lower lobe, there was no invasion within 1 cm of
      the orifice of the upper bronchus, (2) there was no invasion to the trunks of the
      pulmonary vessels, (3) there was no invasion to any other lobes, (4) a complete
      resection was achieved. RESULTS: No differences were observed between the two
      groups regarding stage, histological population, or age. The incidence of
      postoperative complications was 13.7% in the SL group (2 cases each of pneumonia
      and arrythmia), and 24.1% in the PN group (3 bronchopulmonary fistula, 2
      bleeding, 1 instance each of arrythmia and acute cardiac failure, and 2 operation
      related deaths) (P < 0.05). The 3-year disease-free survival was 65.7% in SL,
      58.8% in PN (no statistical significance in the log-rank test). Recurrent disease
      was observed in the local regions of three patients in the SL group and six
      patients in the PN group, and at distant organs of six patients in the SL group
      and seven in the PN group. CONCLUSIONS: These findings thus suggest that as a
      curative treatment, lobectomy with bronchoplasty may be a safer procedure than
      pneumonectomy for lung cancer.

PMID- 9040799
TI  - Clinical study of the relationship between cytological behavior and postoperative
      prognosis in colorectal cancer cases with special reference to nuclear DNA
      content and nucleolar organizer regions.
AB  - BACKGROUND: We studied the usefulness of nuclear DNA patterns and argyrophylic
      nucleolar organizer regions (AgNORs) for evaluating the malignant potential of
      colorectal cancers, which is increasingly being regarded as important in
      predicting patients' prognosis and for their appropriate postoperative
      management. METHODS: We measured these two factors in curatively resected
      specimens of 91 colorectal cancer cases, which were followed up for 1,549 +/- 788
      days postoperatively. Ploidy pattern was either diploid or aneuploid, and AgNORs
      score was either low (LS) or high (HS). Thus, we classified our cases into Group
      I (diploid, LS). Group II (aneuploid, LS), Group III (diploid, HS), and Group IV
      (aneuploid, HS). Postoperative survival curves in the cases belonging to these
      groups were analyzed. RESULTS: Survival rates in Groups I and II were
      significantly higher than those in Group IV. Correlation between subgroups and
      clinicopathological factors such as average age, histologic type, depth of
      invasion, and histologic stage were observed. Incidence of lymph node metastasis
      at the time of operation and that of postoperative recurrence were higher in
      group IV than that in groups I and II. CONCLUSIONS: Measurement of DNA ploidy
      patterns and AgNORs score were found to be useful in evaluating malignant
      potential of colorectal cancers.

PMID- 9040800
TI  - Analysis of lymph node metastasis in early gastric cancer: rationale of limited
      surgery.
AB  - BACKGROUND: Since the majority of patients with early gastric cancer show long
      term survival after surgery, a special attention must be directed to preserving
      gastric function in these patients. Little is known about the protocol of
      surgical treatment appropriate for early gastric cancer patients. This study was
      designed to determine the appropriate surgical procedure for early gastric
      cancer. METHODS: The clinicopathologic features of 52 patients with node-positive
      early gastric cancer were reviewed retrospectively from hospital records between
      1969 and 1994 and were compared with those of 582 patients with node-negative
      early gastric cancer. Nodal status of positive nodes in the 52 cases was
      investigated. RESULTS: Depth of invasion, lymph vessel invasion, and tumor size
      were associated with lymph mode metastasis. Node-positive patients with early
      gastric cancer had a poorer survival rate than node-negative patients (P < 0.05).
      Patients with five or more positive nodes and positive nodes distant from the
      common hepatic artery showed an extremely poor prognosis. CONCLUSIONS: The
      surgical procedures most appropriate for the treatment of early gastric cancer
      are as follows: (1) local gastric resection without lymphadenectomy for mucosal
      cancers of < 2 cm in diameter and for elevated submucosal cancers of < 1 cm in
      diameter, (2) gastrectomy with dissection of the perigastric nodes, the nodes
      along the left gastric artery and the common hepatic artery, for the treatment of
      other early gastric cancers.

PMID- 9040801
TI  - bcl-2 oncoprotein in surgically resected non-small cell lung cancer: possibly
      favorable prognostic factor in association with low incidence of distant
      metastasis.
AB  - BACKGROUND: The bcl-2 oncoprotein serves a regulatory function in permitting
      several cell types to die in an apoptotic process. Its overexpression probably
      plays a role in tumorigenesis and tumor development. The aim of this study was to
      determine the clinicopathological and prognostic significance of the bcl-2
      oncoprotein in patients with nonsmall cell lung cancer (NSCLC). METHODS:
      Immunostaining for bcl-2 oncoprotein was performed on 182 operable NSCLCs.
      RESULTS: Thirty-six patients (19.8%) showed a positive immunostaining for bcl-2
      oncoprotein. Histologically, its incidence was higher in squamous cell carcinomas
      (29.6%). Its expression status was inversely correlated with tumor development
      associated parameters such as tumor stage in NSCLCs, especially in squamous cell
      carcinomas, bcl-2 positive patients with NSCLCs, especially squamous cell
      carcinomas, showed better overall survival and disease-free survival (DFS). In a
      multivariate analysis, this oncoprotein status had prognostic value in DFS for
      NSCLCs and in overall survival for squamous cell carcinomas. The recurrence of
      bcl-2 positive NSCLCs was significantly uncommon in distant extrathoracic organs.
      CONCLUSIONS: The expression of bcl-2 oncoprotein in NSCLCs may be an early event
      of tumor development, especially in squamous cell carcinomas, and may be of
      importance in determining tumor progression and prognosis.

PMID- 9040802
TI  - Uterine sarcoma in the south of Israel: study of 36 cases.
AB  - BACKGROUND: Uterine sarcomas are rare, charaterized by rapid clinical progression
      and poor prognosis, and their management has been a challenge. The purpose of
      this study was to investigate the clinical and histologic findings, treatment,
      and outcome of patients with uterine sarcoma in the south of Israel. METHODS:
      Data from the files of 36 patients with uterine sarcoma who were managed at the
      Soroka Medical Center between January 1961 and December 1994 were evaluated.
      RESULTS: The 5-year survival rate was 32% overall; 63% for 9 patients with
      endometrial stromal sarcoma (ESS). 30% for 14 patients with mixed mesodermal
      sarcoma (MMS) and 18% for 13 patients with leiomyosarcoma (LMS): 41% for 22
      patients with Stage I and 19% for 14 patients with Stages II, III, and IV. Only
      the difference in the 5-year survival rate between ESS and LMS was statistically
      significant (P < 0.05). Eleven patients (30.6%) were treated with surgery alone,
      4 (11.1%) with surgery followed by pelvic radiotherapy, 11 (30.6%) with surgery
      followed by chemotherapy, 8 (22.2%) with surgery followed by pelvic radiotherapy
      and chemotherapy, one (2.8%) with chemotherapy alone, and one (2.8%) had no
      treatment. CONCLUSIONS: Uterine sarcomas are aggressive tumors with a poor
      prognosis. The treatment is surgery generally followed by adjuvant pelvic
      radiotherapy and/or systemic chemotherapy.

PMID- 9040803
TI  - Improved staging of liver tumors using laparoscopic intraoperative ultrasound.
AB  - BACKGROUND: Intraoperative ultrasound has been shown to provide significant
      assistance in operative staging and management of patients with liver tumors
      during open surgery. The availability of the 5.0-7.5 Mhz semiflexible ultrasound
      transducer with gray-scale, color and spectral Doppler capabilities can provide
      similar information laparoscopically. METHODS: Twenty-four consecutive patients
      with liver tumors (18 metastatic and six primary), in technically resectable
      locations determined by a variety of conventional imaging studies, were brought
      to the operating room. There was no known extrahepatic disease, and there was no
      recurrence at the primary site in the metastatic subgroup. These patients were
      evaluated intraoperatively with laparoscopy and intraoperative laparoscopic
      ultrasound to assess resectability prior to performing a major laparotomy.
      Laparoscopy was successful in 23 of the patients and in 19 of 23, laparoscopic
      ultrasound was also employed, using the 5.0-7.5 MHz semiflexible transducer. The
      use of the open entry technique, selection of alternate entry sites, coupled with
      expertise in laparoscopic lysis of adhesions, has allowed safe laparoscopic tumor
      staging. RESULTS: The laparoscopic evaluation was aborted only once due to dense
      adhesions, despite the fact that 67% of the patients had undergone previous
      abdominal surgery. There was only one complication: bleeding from a liver biopsy
      in an unresectable cirrhotic patient, necessitating laparotomy. Laparoscopy and
      ultrasound together predicted nonresectability in six of eight unresectable
      patients, all of whom were spared an unnecessary laparotomy. CONCLUSIONS:
      Laparoscopic ultrasonographic evaluation for the staging of liver tumors should
      be a prerequisite to definitive laparotomy, with the objective of avoiding
      unnecessary surgery.

PMID- 9040804
TI  - Extremity soft tissue sarcoma with metastases to abdominopelvic surfaces.
AB  - BACKGROUND: In a majority of patients with extremity soft tissue sarcoma, the
      lungs are the first site at which recurrent disease is detected. Other common
      sites of recurrence are the resection site, bone metastasis, and liver
      metastasis. Although abdomino pelvic sarcomatosis is common as a site of
      recurrence for visceral and retroperitoneal sarcoma, it has not been previously
      reported for extremity sarcoma. METHOD: We present three patients in whom
      extremity soft tissue sarcoma metastasized to the peritoneal surfaces, and in all
      three patients this was symptomatically the dominant site for recurrence. All of
      them underwent a palliative surgical cytoreduction and were then treated with
      intraperitoneal chemotherapy. RESULTS: In two of the three patients, isolated
      progression of peritoneal sarcomatosis has again occurred: one patient remains
      disease free at 14 months. CONCLUSIONS: Metastasis to peritoneal surfaces within
      the abdomen and pelvis must be considered a possible site for systemic
      dissemination of extremity soft tissue sarcomas. Effective treatments for sarcoma
      spread to peritoneal surfaces would benefit this small but symptomatic group of
      patients.

PMID- 9040805
TI  - Pituitary adenoma and bilateral male breast cancer: an unusual association.
AB  - An unusual case is presented of bilateral breast cancer in a male patient with a
      long history of endocrine dysfunction due to a prolactinoma. The role of abnormal
      endocrine function in the development of male breast cancer is reviewed. The
      strongest association between aberrant endocrine function and male breast cancer
      occurs in patients with Klinefelter's syndrome, who have an approximate 3%
      lifetime risk of developing breast cancer. Retrospective case-control studies
      indicate that both estrogen excess and androgen deficiency may be involved in
      male breast cancer. Clinical studies of estrogen, androgen, and prolactin levels
      in male breast cancer patients have yielded conflicting results, and the precise
      nature of the hormonal mechanisms involved in the development of male breast
      cancer remains to be defined.

PMID- 9040807
TI  - Constant landmark for simplified identification of the long thoracic nerve during
      mastectomy.

PMID- 9040806
TI  - Brachytherapy (seed implantation) for clinically localized prostate cancer.

PMID- 9040808
TI  - Lasers: reflections on their evolution.
AB  - A review of the past 22 years of laser applications shows that a great deal of
      progress has been made. It allows one to see the evolution of laser therapy,
      compare it with other modalities used in surgical oncology, and identify certain
      program that merit clinical trial. Use of lasers in surgical oncology began with
      a laser knife. Tissues were divided and removed with the focused beam of the CO2
      laser, which replaced the scalpel previously used to perform surgical procedures.
      Later, the Nd:YAG laser was used in hollow visci such as the trachea and
      esophagus to open obstructed passages and possibly to cure many cancers. The
      operating microscope was used in the larynx to remove benign and malignant
      lesions, and for obstructing lesions to provide time to treat medical
      complications by reopening airway passages, and to add irradiation and/or
      chemotherapy preoperatively. Many times the Nd:YAG laser was used
      gastroscopically to treat bleeding or obstruction. Cytoreduction by laser made
      surgery or chemotherapy, or both, plausible. Addition of the sapphire tip and,
      later, the bare of sculptured fiber increased the variety of procedures possible
      with the Nd:YAG laser. Photodynamic therapy (PDT) uses various drugs that are
      localized in cancer cells. The cancer is then destroyed by laser emissions of the
      proper wavelength. One of the problems with PDT is getting the light to the
      tumor. Preactivation is addressed in this report. The problems associated with
      anaerobic tumors are discussed and suggestions for clinical trials offered. Laser
      hyperthermia is compared with induced hyperthermia as well as in combination with
      irradiation. Protocols of local laser hyperthermia combined with irradiation need
      further exploration. This review addresses the use of lasers in the destruction
      of tumor cells for bone marrow transplant and several old and new experiments
      used to block the AIDS virus. Finally, ongoing research is discussed, including
      the present and future roles of lasers.

PMID- 9040809
TI  - Carpal tunnel syndrome.

PMID- 9040810
TI  - Neuropathic symptoms and musculoskeletal pain in carpal tunnel syndrome:
      prognostic and therapeutic implications.
AB  - BACKGROUND: Repetitive activities in the workplace can not only jeopardize the
      median nerve across the carpal tunnel but also the musculoskeletal structures,
      such as the ligaments, synovia, tendons and muscles producing pain, and local
      tenderness at the wrist, elbow, and shoulder. The occurrence of this latter
      condition can dominate the overall clinical picture and affect the outcome of
      treatments for this very common condition. METHODS: A clinical evaluation of 30
      patients who previously underwent a successful and uncomplicated carpal tunnel
      release surgery was conducted. These patients were referred back for another
      electrodiagnostic study to consider the possibility of persistent or recurrent
      nerve entrapment. These patients all had musculoskeletal pain and local
      tenderness at the wrist, elbow, and shoulder as their primary and disabling
      symptoms; and neuropathic symptoms as their less disabling complaints. RESULTS:
      All patients reported significant resolution of their neuropathic symptoms
      following surgery but their musculoskeletal symptoms persisted preventing them
      from returning to their original occupation. Fifty percent showed mild to
      moderate improvement in their electrophysiologic abnormalities but none had
      complete normalization of nerve conduction. Few patients developed symptoms of
      sympathetic nerve overactivity. CONCLUSIONS: Some patients suffering from carpal
      tunnel syndrome may present with a disabling musculoskeletal pain and local
      tenderness in the upper extremities that can persist following surgery despite
      resolution of neuropathic symptoms. These two symptom complexes, although both
      sequelae of repetitive activities, have fundamental clinicopathologic differences
      that must be recognized because of their therapeutic, prognostic, and medico
      legal implications.

PMID- 9040811
TI  - Local wound infiltration with bupivacaine in lumbar laminectomy.
AB  - BACKGROUND: Parenteral administration of narcotics has been the mainstay for
      postoperative pain relief in patients undergoing lumbar laminectomy. However,
      this may lead to respiratory depression and nausea, which may be hazardous in
      these patients. METHODS: We evaluated the efficacy of wound infiltration with
      bupivacaine in 45 consecutive patients undergoing elective single-level lumbar
      laminectomy for intervertebral disc prolapse in a prospective, double-blind,
      randomized controlled trial. Prior to wound closure, the muscle and subcutaneous
      tissues were infiltrated with bupivacaine 0.375% or sterile physiologic saline.
      Postoperatively, the patients were assessed hourly for pain and an analgesic
      administered if the patient had moderate or severe pain. RESULTS: All the 21
      placebo recipients required analgesics in the first 9 hours postoperatively,
      compared to only 11 of 24 patients who received bupivacaine (p < 0.001). The mean
      (standard deviation) time before administration of the first dose of analgesic
      postoperatively in the bupivacaine and placebo recipients was 807.7 (567.6)
      minutes and 181.4 (110.1) minutes, respectively (p < 0.001). No adverse effects
      of local wound infiltration were noted. CONCLUSIONS: Local wound infiltration
      with bupivacaine is a safe and effective method for providing postoperative pain
      relief and reducing narcotic use in patients undergoing lumbar laminectomy.

PMID- 9040812
TI  - The effect of urokinase in preventing the formation of epidural fibrosis and/or
      leptomeningeal arachnoiditis.
AB  - BACKGROUND: Epidural fibrosis and leptomeningeal adhesion formation are among the
      common causes of failed back surgery syndrome. Urokinase has been commonly used
      in treating aneurysmal subarachnoid hemorrhage and intracerebral hematoma.
      METHODS: In a rat model, the potential of local urokinase in preventing the
      production of epidural fibrosis due to bleeding was investigated. RESULTS: A
      reduction of approximately 48% in leptomeningeal adhesion formation with the use
      of urokinase was demonstrated. Adhesion score was 2.300 in the control group and
      0.700 in the urokinase treated group on day 42 of the postoperative period.
      CONCLUSIONS: It can be concluded that urokinase has the important effect of
      preventing the formation of leptomeningeal adhesion, but many more extensive
      studies clearly need to be done before such material can be clinically used.

PMID- 9040813
TI  - Impaired cerebral autoregulation after mild brain injury.
AB  - BACKGROUND: Severe head injury may impair cerebral autoregulation, which can
      increase the risk of secondary neuronal injury. The likelihood of impairment in
      autoregulation is assumed to be low with mild head injury. We report here the
      absence of cerebral autoregulation in a patient who suffered a concussion from an
      automobile accident 6 days earlier. METHODS: The patient participated in a
      clinical study approved by the institutional human subjects review committee,
      investigating the dose-effect relationship of anesthetics on cerebral
      autoregulation. The patient was scheduled to undergo repair of a knee injury
      suffered during a motor vehicle accident, during which she had a concussion. The
      screening evaluation revealed no evidence of neurologic disease. The test was to
      be performed three times in each patient: baseline autoregulation measurements
      during stable fentanyl-nitrous oxide anesthesia, second and third measurements
      during low dose and high dose of the anesthetic to which the patient was
      assigned. Autoregulation was tested by increasing the mean systemic blood
      pressure from 80 mm Hg-100 mm Hg using a phenylephrine infusion while
      simultaneously recording flow velocity from a middle cerebral artery using
      transcranial Doppler ultrasonography. RESULTS: Static autoregulation testing
      during baseline testing demonstrated complete absence of this homeostatic
      mechanism and the study was canceled. Repeated testing in the recovery unit after
      the patient awoke showed identical results. CONCLUSIONS: Trivial mild head injury
      may result in loss of cerebral autoregulation. A clinical study of a larger
      series to document the incidence is warranted.

PMID- 9040814
TI  - Onset of uncomplicated cerebrospinal fluid fistula 27 years after head injury:
      case report.
AB  - BACKGROUND: Cerebrospinal fluid fistulae complicated by meningitis have been
      reported to appear as late as 36 years after the causal head injury. METHODS: We
      present this 54-year-old woman with a recurrent cerebrospinal fluid rhinorrhea
      that started 27 years after a road accident. The surgical exploration revealed a
      linear fracture of the cribriform plate. RESULTS: Once the defect was repaired,
      the leak ceased, with no recurrence in 2 years of follow-up. CONCLUSIONS: A
      traumatic cerebrospinal fluid leak may appear for the first time after 2-3
      decades have elapsed. An operation is indicated in order to localize the site of
      leakage, when other investigations have failed or are not available, as well as
      to prevent a secondary infection, when still possible.

PMID- 9040815
TI  - Cyst of the velum interpositum treated by endoscopic fenestration.
AB  - BACKGROUND: The cavum veli interpositi is a not infrequent radiologic finding in
      both children and adults, as confirmed by computed tomography (CT) and magnetic
      resonance (MR). A moderate enlargement of the cavum may sometimes be observed; on
      the other hand, a true large cyst may be considered exceptional, with only one
      reported case. CASE HISTORY: This 9-year-old boy with psychomotor retardation and
      epileptic seizures had a large CSF cyst in the region of the cavum veli
      interpositi, diagnosed by CT and MR. The patient was treated by endoscopic
      surgery, with introduction of the endoscope into the occipital horn of the right
      lateral ventricle and multiple fenestrations from the right ventricle to the
      cyst, and then from the cyst to the left lateral ventricle. The surgery resulted
      in decrease in the size of the cyst and reduction of the frequency of seizures.
      DISCUSSION AND CONCLUSIONS: Children with dilated or cystic cavum veli
      interpositi present with a large head, mental retardation, seizures, and
      hydrocephalus. On CT and MR, the cyst shows a typical triangular configuration on
      the axial plane and lies on the roof of the third ventricle in the coronal plane.
      Endoscopic ventricular fenestration is the treatment of choice for these as well
      as all other intraventricular and intracerebral CSF cysts, because it ensures
      communication between the cyst and the ventricular system and avoids definitive
      shunting of the cyst.

PMID- 9040816
TI  - Current state of study on moyamoya disease in Japan.
AB  - BACKGROUND: Moyamoya disease is a unique cerebrovascular disease with much higher
      incidence in Japanese and Asians than in Caucasians. The Research Committee on
      Spontaneous Occlusion of the Circle of Willis (Moyamoya disease) of the Ministry
      of Health and Welfare, Japan, has studied the pathogenesis, epidemiology,
      clinical investigations, and treatment of the disease since 1977. The current
      status of the study of moyamoya disease in Japan is presented. METHODS: There
      were 821 registered cases of moyamoya disease in Japan up to 1994. The study
      group also obtained statistical data from a questionnaire sent to hospitals
      dealing with the disease. [The data collected were analyzed.] RESULTS: The
      estimated number of patients in Japan through 1994 was 3800. Characteristic
      epidemiologic data were: female dominance (male to female ratio = 1:1.7); highest
      rate of onset in the age group below 10 years, with a second mild peak from 30-40
      years; and rate of familial cases around 10%, including identical twins. The most
      recent development is diagnosis by MRI and MRA-it is now possible to obtain a
      diagnosis without conventional angiography. The study of the cerebral perfusion
      and metabolism by positron emission tomography (PET) or SPECT is becoming more
      important in understanding the state of illness and in deciding the indications
      for surgery. Treatment of moyamoya disease can be either medical or surgical. The
      latter consists of either direct bypass surgery (STA-MCA anastomosis) or indirect
      bypass procedures, including EDAS, EMS, EMAS, and omental transplantation. At
      present, although not statistically significant, the surgically-treated groups
      seem to have better results than the medically-treated groups. CONCLUSIONS: The
      clinical features of moyamoya disease are becoming more elucidated. However,
      further studies are necessary including the pathogenesis, which is still not
      known.

PMID- 9040817
TI  - Intra-aneurysmal GDC embolization followed by intrathecal tPA administration for
      poor-grade basilar tip aneurysm.
AB  - BACKGROUND: This 42-year-old male presented with subarachnoid hemorrhage of Hunt
      and Kosnik Grade IV, complicated by neurogenic pulmonary edema, prolongation of
      the electrocardiographic Q-Q interval, and acute renal failure. METHODS: Surgical
      clipping was not indicated, so intra-aneurysmal embolization using Guglielmi
      detachable coils (GDCs) was performed followed by intrathecal infusion of tissue
      type plasminogen activator (tPA) via spinal drainage. RESULTS: The patient made a
      complete recovery 2 1/2 months later except for partial third cranial nerve
      palsy. CONCLUSIONS: Intra-aneurysmal GDC embolization followed by intrathecal tPA
      via spinal drainage is an excellent method for treating aneurysms that are
      difficult to treat surgically.

PMID- 9040819
TI  - Philosophy of skull base surgery: a lecture by Dr. Madjid Samii Lima, Peru; July
      2, 1995.

PMID- 9040818
TI  - Vertebral artery occlusion after subarachnoid hemorrhage from a dissecting
      aneurysm of the vertebral artery: case report.
AB  - BACKGROUND: Generally speaking, occlusion of the vertebral artery is a finding of
      a dissecting aneurysm associated with completed stroke. We present a case of a
      vertebral dissecting aneurysm that produced subarachnoid hemorrhage (SAH).
      Angiography on the day of hemorrhage, however, demonstrated complete occlusion of
      the vertebral artery. CASE PRESENTATION: A 44-year-old hypertensive woman
      suffered a sudden onset of headache and vomiting followed by loss of
      consciousness due to SAH. Angiography on the day of hemorrhage revealed a
      complete occlusion of the right vertebral artery just distal to the dissecting
      aneurysm. This is the first report of such a case. The patient was still
      considered to be at significant risk of rerupture. Craniotomy and clip occlusion
      of the right vertebral artery and the origin of the right posterior inferior
      cerebellar artery were carried out to trap the thin-walled sac. At discharge, the
      patient had recovered completely except for some left limb ataxia, which
      subsequently disappeared. CONCLUSIONS: Two options are available for the
      treatment of such a case: surgical or medical treatment. We employed surgery.
      Which is the preferred approach, however, is a difficult judgment to make at this
      juncture.

PMID- 9040820
TI  - Loss of heterozygosity in the retinoblastoma tumor suppressor gene in skull base
      chordomas and chondrosarcomas.
AB  - BACKGROUND: The retinoblastoma (Rb) gene is a well characterized tumor suppressor
      gene in which loss of heterozygosity has been implicated in a number of
      malignancies including osteosarcoma and breast carcinoma. Chordomas and
      chondrosarcomas are rare skull base neoplasms with a propensity for local
      recurrences, resistance to conventional radiotherapy, and a 5%-30% incidence of
      metastases. Except for the so called "chondroid chordoma," histologic features do
      not correlate with the clinical behavior or growth patterns of these tumors. No
      study to date has investigated what role tumor suppressor genes or oncogenes play
      in the development and continued growth of these rare neoplasms. METHODS: In
      order to evaluate the role of the retinoblastoma tumor suppressor gene in
      chordomas and chondrosarcomas we screened seven chordomas and two chondrosarcomas
      located at the skull base for loss of heterozygosity (LOH) of the Rb gene.
      Genomic DNA was extracted from tumor specimens as well as matched control tissue
      and utilizing a polymerase chain reaction technique, intron 17 and 20 were
      amplified from each specimen. The intron 17 product was then digested with the
      restriction endonuclease X ba1 followed by electrophoresis on a 1% agrose gel.
      The intron 20 amplified products were electrophoresed on a nondenaturing 6%
      polyacrylamide gel. RESULTS: We demonstrated LOH at intron 17 of the
      retinoblastoma gene in 2/7 chordomas and in 0/2 chondrosarcomas. The two
      chordomas possessing LOH were particularly aggressive tumors demonstrating
      extensive involvement of the skull base and rapid recurrences following radical
      resections. CONCLUSIONS: Alterations of the Rb gene may play a role in the growth
      of skull base chordomas with LOH of the Rb gene serving as a marker for more
      aggressive tumors. This report represents the first study evaluating the Rb gene
      in chordomas or chondrosarcomas and is the first report of allelic loss of the Rb
      gene in skull base chordomas.

PMID- 9040821
TI  - Pleomorphic xanthoastrocytoma: report of six cases with special consideration of
      diagnostic and therapeutic pitfalls.
AB  - BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare clinicopathologic
      entity that occurs typically in young patients. Improved neuroradiologic
      techniques, especially gadolinium-enhanced magnetic resonance imaging (MRI),
      reveal a characteristic tumor appearance. METHODS: We present six cases of PXA
      operated on with unusual clinical course, elucidating different clinical
      implications. RESULTS: Two patients showed subsequent progression into a
      malignant glioma, one case was a primary anaplastic PXA. The latter case had not
      previously been reported in the literature. Increased mitotic activity seems to
      indicate a worse clinical course; whereas focal infiltration of the brain does
      not necessarily lead to malignant transformation. CONCLUSIONS: Surgical removal
      is the treatment of choice. A consequent follow-up is mandatory in order to
      detect a potentially malignant recurrence as early as possible and to select
      patients who need additional therapy.

PMID- 9040822
TI  - Image-guided stereotactic neurosurgery with the multicoordinate manipulator
      microscope.

PMID- 9040823
TI  - Three-dimensional imaging for presentation of the causative vessels in patients
      with hemifacial spasm and trigeminal neuralgia.
AB  - BACKGROUND: In patients with hemifacial spasm and trigeminal neuralgia,
      preoperative detection of the relationship between the blood vessels and the
      cranial nerves involved is essential. METHODS: We studied the causative vessels
      in 20 patients with hemifacial spasm and six patients with trigeminal neuralgia
      by means of magnetic resonance (MR) imaging with spoiled gradient recalled
      acquisition in the steady state (SPGR), MR angiography, and three-dimensional (3
      D) imaging reconstructed from the data of SPGR MR imaging by the surface
      rendering method at a workstation. RESULTS: In all patients, the preoperative
      SPGR MR images demonstrated that the causative vessels compressed or were in
      contact with the root exit or root entry zone (REZ) of the facial or trigeminal
      nerve. These causative vessels were identified by inspection of the MR
      angiographic and 3-D images. The 3-D images provided clear information as to the
      anatomic relationship between the causative vessels and the REZ of these nerves.
      These findings were corroborated by the intraoperative findings. The symptoms
      were completely relieved after surgery in 18 of the patients with hemifacial
      spasm and in all six patients with trigeminal neuralgia. In all patients,
      sufficient decompression was depicted on the postoperative SPGR MR images at the
      causative vessels and the REZ of the nerve. CONCLUSION: SPGR MR images, MR
      angiography, and 3-D images are useful for the identification of the causative
      vessels in patients with hemifacial spasm or trigeminal neuralgia. The 3-D images
      are particularly useful for the simulation planning of the operative procedure.

PMID- 9040824
TI  - A review of MRI pulse sequences and techniques in neuroimaging.
AB  - BACKGROUND: The unmatched soft tissue contrast provided by magnetic resonance
      imaging (MRI) has made it the modality of choice for many neuroimaging
      examinations. The fact that signal intensity in MRI depends on many parameters,
      including spin-lattice and spin-spin relaxation times, proton density, and
      velocity, makes it possible to highlight various pathologies by appropriate
      choice of pulse sequences and pulse sequence parameters. It is somewhat
      overwhelming however, to filter through various pulse sequences and parameters in
      order to understand how their selection affects image contrast. This brief review
      is intended to highlight common pulse sequences and parameters as well as
      introduce new techniques currently being released for clinical use. MATERIALS:
      Basic pulse sequences are described and the influence of the acquisition
      parameters on image contrast are illustrated. Such basic sequences include the
      ubiquitous spin echo, fast spin echo, and gradient echo sequences. Specialized
      techniques for fat suppression and magnetic resonance angiography are also
      presented. Currently approved contrast agents for use in MRI are briefly
      reviewed, and various advanced pulse sequences, such as those for diffusion and
      magnetization transfer contrast imaging, are briefly outlined. RESULTS: The
      utility of basic and advanced pulse sequences are demonstrated by clinical
      examples and images of normal brain and spine. New sequences and techniques are
      briefly outlined with regard to their potential for improving neuroimaging
      examinations. CONCLUSIONS: This brief review outlines how the choice of pulse
      sequence and acquisition parameters influences the resulting image contrast for a
      variety of basic and advanced imaging techniques.

PMID- 9040825
TI  - Effective lecture presentation skills.
AB  - Lectures are the most popular form of teaching in medical education. As much as
      preparation and organization are key to the lecture's success, the actual
      presentation also depends upon the presenter's ability to reach the audience.
      Teaching is a lively activity. It calls for more than just offering ideas and
      data to an audience. It calls for direct contact with the audience, effective use
      of language, capability to use limited time effectively, and the ability to be
      entertaining. This article offers a structure to effective lecturing by
      highlighting the importance of voice clarity and speaking speed, approaches to
      using audiovisual aids, effectively using the audience to the lecture, and ways
      to be entertaining.

PMID- 9040826
TI  - What is happening in neurosurgery around the world?

PMID- 9040827
TI  - Possible transmission of Blastomycosis dermatitidis via culture specimen.

PMID- 9040828
TI  - Wry neck in rabbits.

PMID- 9040829
TI  - Fetal infection may not be preventable with BVDV vaccines.

PMID- 9040831
TI  - Food animal veterinarians and the use of a yellow legal pad.

PMID- 9040830
TI  - Serum antibodies to Sarcocystis neurona--half the horses in the United States
      have them!

PMID- 9040832
TI  - What is your diagnosis? Mineralized intervertebral disk with right dorsolateral
      herniation in a dog.

PMID- 9040833
TI  - Employment of male and female graduates of US veterinary medical colleges, 1996.

PMID- 9040834
TI  - The role of the food animal veterinarian in the HACCP era.

PMID- 9040835
TI  - Blastomycosis in six dogs in New York state.
AB  - Blastomycosis was diagnosed in 6 dogs living in New York state. To our knowledge,
      blastomycosis has not been previously reported in dogs in this area, and maps
      that indicate the prevalence of blastomycosis in North America often partially or
      completely exclude the state of New York. Environmental characteristics
      implicated in previous blastomycosis outbreaks in people can be found in New York
      state, and this may explain how these dogs became infected. Blastomycosis
      develops in people as well as in dogs, and an understanding of the ecologic and
      clinical features of blastomycosis can help veterinarians counsel their clients
      in matters of public health.

PMID- 9040836
TI  - Clinical and pathologic findings in Doberman pinschers with occult cardiomyopathy
      that died suddenly or developed congestive heart failure: 54 cases (1984-1991).
AB  - OBJECTIVE: To determine echocardiographic, electrocardiographic, and histologic
      abnormalities in Doberman Pinschers with occult cardiomyopathy that died suddenly
      and to compare findings with those of Doberman Pinschers with cardiomyopathy that
      died of congestive heart failure. DESIGN: Retrospective study. ANIMALS: 14
      Doberman Pinschers with occult cardiomyopathy that died suddenly (group 1) and 40
      Doberman Pinschers with cardiomyopathy and congestive heart failure (group 2).
      PROCEDURE: Serial echocardiography and continuous, ambulatory
      electrocardiographic (Holter) monitoring were performed. Hearts of dogs that died
      suddenly were examined histologically. RESULTS: Group-2 dogs died at a
      significantly older age than did group-1 dogs. All dogs had echocardiographic
      abnormalities, but changes were more severe in group-2 than in group-1 dogs.
      Ventricular tachyarrhythmias were documented in all dogs. Group-1 dogs were more
      likely to have episodes of sustained ventricular tachycardia than were group-2
      dogs. Multifocal interstitial fibrosis and replacement of muscle fibers with
      collagen and fat were consistently observed in hearts from dogs that died
      suddenly. Ten group-1 dogs had received antiarrhythmic treatment prior to death.
      CLINICAL IMPLICATIONS: Occult cardiomyopathy can be identified by means of
      echocardiography and Holter monitoring in Doberman Pinschers. Doberman Pinschers
      with cardiomyopathy that had episodes of sustained (> 30 seconds) ventricular
      tachycardia were at risk of dying suddenly.

PMID- 9040837
TI  - Doxorubicin alone or in combination with asparaginase, followed by
      cyclophosphamide, vincristine, and prednisone for treatment of multicentric
      lymphoma in dogs: 121 cases (1987-1995).
AB  - OBJECTIVE: To determine response rate and remission as well as survival times for
      dogs with multicentric lymphoma treated first with doxorubicin alone or in
      combination with asparaginase and then with cyclophosphamide, vincristine
      sulfate, and prednisone (CVP) and to identify prevalence of toxicoses associated
      with this protocol and factors associated with prognosis. DESIGN: Retrospective
      case series. ANIMALS: 121 dogs. PROCEDURE: Variables evaluated for prognostic
      value were initial response rate to chemotherapy, age, breed, sex, body weight,
      histologic grade, clinical stage and substage, previous corticosteroid treatment,
      and serum calcium concentration. RESULTS: Median overall remission and survival
      times for all 121 dogs were 205 and 237 days, respectively. Response rate
      (complete or partial response) was 88%. Ten dogs were hospitalized because of
      toxicoses associated with doxorubicin, and 19 dogs were hospitalized because of
      toxicoses associated with CVP. Asparaginase favorably influenced the initial
      response rate, but did not significantly influence overall remission of survival
      times. Initial response rate to chemotherapy, body weight, clinical substage, and
      serum calcium concentration was found to have prognostic value. CLINICAL
      IMPLICATIONS: For dogs with multicentric lymphoma, treatment with doxorubicin
      alone or in combination with asparaginase and then with CVP resulted in an
      acceptable response rate and low prevalence of toxicoses.

PMID- 9040838
TI  - Seroprevalence of antibodies to Sarcocystis neurona in horses residing in a
      county of southeastern Pennsylvania.
AB  - OBJECTIVE: To determine seroprevalence of Sarcocystis neurona-specific antibodies
      in a population of horses residing in Chester County, Pa. DESIGN: Prevalence
      survey. SAMPLE POPULATION: 117 serum samples from selected members of a
      population of 580 Thoroughbred horses. PROCEDURE: Serum was analyzed for
      antibodies to Sarcocystic neurona, using a western blot. Information regarding
      age, sex, and housing of horse was obtained by questionnaire. Data were analyzed,
      using multivariable logistic regression. RESULTS: Seroprevalence was 45.3% (95%
      CI, 36.3 to 54.3%). A relationship was not found between seroprevalence and sex
      of horse. Seroprevalence was greater in older horses (logistic regression; P =
      0.16). CLINICAL IMPLICATIONS: High seroprevalence of antibodies to S neurona and
      the lack of neurologic deficits among horses sampled indicate that positive
      results of serologic examination alone are of limited value for diagnosis of
      equine protozoal myeloencephalitis. Clinical signs consistent with the disease
      are the most important consideration in accurate diagnosis.

PMID- 9040839
TI  - Seroprevalence of antibodies to Sarcocystis neurona in horses residing in Ohio.
AB  - OBJECTIVE: To determine the seroprevalence of serum antibodies to Sarcocystis
      neurona in horses residing in Ohio. DESIGN: Prevalence survey. SAMPLE POPULATION:
      Serum from samples from 1,056 horses. Serum was collected on every 36th sample
      submitted to the Ohio State Diagnostic Laboratory for testing for equine
      infectious anemia. PROCEDURE: Serum was frozen at -80 C and analyzed for
      antibodies to S neurona, using a western blot. Information regarding blood sample
      collection, age, breed, sex, and geographic location was recorded for each horse.
      Data were analyzed, using multivariable logistic regression. RESULTS: Horses of
      37 breeds from 81 of Ohio's 88 counties were included in the study population.
      There were 481 females, 133 males, and 442 geldings ranging in age from 3 months
      to 27 years; > 48% were < 5.6 years old. More than 53% of samples were
      seropositive for antibodies to S neurona. A gender or breed effect on
      seroprevalence was not identified. There was a significant effect of age (P < or
      = 0.0001; with older horses more likely to be affected), and of location
      (statistical and extension districts; P = 0.02 and P = 0.03, respectively) on
      seroprevalence. Location effects appeared to be correlated to the number of days
      with temperatures below freezing (P < 0.05). CLINICAL IMPLICATIONS: The high
      seroprevalence of antibodies to S neurona found in the sample population
      emphasizes the importance of examining CSF for S neurona-specific antibodies when
      establishing a diagnosis of equn protozoal myeloencephalitis.

PMID- 9040840
TI  - Seroprevalence of antibodies to Sarcocystis neurona in horses residing in Oregon.
AB  - OBJECTIVE: To determine seroprevalence of antibodies to Sarcocystis neurona in
      neurologically normal horses residing in 4 regions of Oregon and to describe the
      effects of age, gender, breed, and housing on seroprevalence within each region.
      DESIGN: Prevalence survey. SAMPLE POPULATION: Serum samples from 334 horses
      systematically selected by practicing veterinarians. PROCEDURE: Antibodies to S
      neurona were measured in sera, using a western blot. Information including age,
      gender, breed, housing, geographic location, and duration of residence was
      obtained for each horse. Data were analyzed, using descriptive statistics.
      RESULTS: 45% (149/334) of horses evaluated were seropositive for antibodies to S
      neurona with significant differences in the percentage of seropositive horses
      from different regions of the state. Seroprevalances of antibodies to S neurona
      in horses in regions I and II, west of the Cascade Range, were 65 and 60%,
      respectively; whereas seroprevalances in central and eastern Oregon, regions III
      and IV, were 43 and 22%, respectively. Seroprevalence consistently increased with
      age of horse for each region. Gender, breed, and housing were not associated with
      significant differences in seroprevalence of antibodies to S neurona in the
      overall sample population, or in comparisons of samples obtained from horses
      within a particular region, or among samples obtained from horses residing in
      different regions. CLINICAL IMPLICATIONS: The high seroprevalence of antibodies
      to S neurona in neurologically normal horses indicates that analysis of serum
      alone would not be useful for definitive diagnosis of equine protozoal
      myeloencephalitis in horses in Oregon.

PMID- 9040841
TI  - Case-control study of an outbreak of clinical disease attributable to Salmonella
      menhaden infection in eight dairy herds.
AB  - OBJECTIVE: To identify risk factors associated with Salmonella menhaden
      associated disease in adult dairy cows during an outbreak in California. DESIGN:
      Case-control study. SAMPLE POPULATION: 8 case dairies that had > or = 1 adult
      animal that had clinical signs of salmonellosis and from which S menhaden was
      isolated and 22 control dairies, 16 of which were matched on the basis of herd
      size and county and 6 of which were matched on the basis of herd size, county,
      and breed (Jersey). PROCEDURE: A questionnaire was developed and reviewed with
      the herdsman or owner of each dairy. Primary areas of concern were herd
      management, disease characteristics, and feed-related information. RESULTS: Use
      of 1 particular feed mill and feeding animal fat were significant risk factors
      for clinical disease attributable to S menhaden infection. CLINICAL IMPLICATIONS:
      Feed should not be overlooked as a potential source of Salmonella organisms in
      dairy herds.

PMID- 9040842
TI  - Intussusception in cattle: 336 cases (1964-1993).
AB  - OBJECTIVE: To evaluate risk factors and to describe clinical and laboratory
      findings, surgical management, and postoperative outcome for cattle with
      intussusception. DESIGN: Hospital-based, case-control epidemiologic study and
      retrospective case series. SAMPLE POPULATION: Medical records of cattle admitted
      to 17 veterinary medical teaching hospitals in North America. PROCEDURE:
      Epidemiologic analysis of demographic data and detailed analysis of medical
      records for selected cattle. RESULTS: 336 cattle with intussusception were
      identified, 281 had small intestinal, 7 had ileocolic, 12 had cecocolic, and 36
      had colocolic intussusceptions. Sex and season were not significantly associated
      with cattle developing intussusception, whereas calves < 2 months old were at
      greater risk of developing small intestinal intussusception than older cattle.
      Analysis of medical records of 57 cattle with intussusception revealed that these
      cattle were mildly hyponatremic, hypochloremic, hypocalcemic, azotemic, and
      hyperglycemic. Right flank laparotomy with a cow in a standing position, followed
      by intestinal resection and end-to-end anastomosis was the most common means of
      surgical correction. Overall survival rate (20/57; 35%) and postoperative
      survival rate (20/46; 43%) for cattle with intussusception were much lower than
      previously reported. CLINICAL IMPLICATIONS: Although rare in cattle,
      intussusception was most common in calves < 2 months old. Survival rate for
      cattle treated for intussusception was low (< 50%).

PMID- 9040843
TI  - Bionomics of anopheles aquasalis Curry 1932, in Guarai, State of Rio de Janeiro,
      southeastern Brazil--I. Seasonal distribution and parity rates.
AB  - From a total of 12,721 anophelines collected in a lowland area in Guarai, Rio de
      Janeiro, from November 1991 to October 1992, 99.7% (12,688) were Anopheles
      aquasalis. This species occurred throughout the year, but in higher numbers from
      April to September, when rainfall was low or moderate. The proportion of parous
      females in June was significantly higher than the annual rate. An. aquasalis was
      weakly attracted by a light-trap, and no significant differences in abundance
      were detected between nights with and without moonlight.

PMID- 9040844
TI  - Current spread of Triatoma infestans at the expense of Triatoma sordida in
      Bolivia.

PMID- 9040845
TI  - Primary isolation of spotted fever group rickettsiae from Amblyomma cooperi
      collected from Hydrochaeris hydrochaeris in Brazil.
AB  - This paper reports the first isolation of a spotted fever group rickettsia from
      an Amblyomma cooperi ixodid collected from a capybara (Hydrochaeris hydrochaeris)
      in an endemic area of spotted fever in the County of Pedreira, State of Sao
      Paulo, Brazil. Isolation was performed in Vero cell culture and submitted to
      immunofluorescence, using antibody from Rickettsia rickettsii-positive human
      serum.

PMID- 9040846
TI  - An oligonucleotide probe derived from kDNA minirepeats is specific for Leishmania
      (Viannia).
AB  - Sequence analysis of Leishmania (Viannia) kDNA minicircles and analysis of
      multiple sequence alignments of the conserved region (minirepeats) of five
      distinct minicircles from L. (V.) braziliensis species with corresponding
      sequences derived from other dermotropic leishmanias indicated the presence of a
      sub-genus specific sequence. An oligonucleotide bearing this sequence was
      designed and used as a molecular probe, being able to recognize solely the sub
      genus Viannia species in hybridization experiments. A dendrogram reflecting the
      homologies among the minirepeat sequences was constructed. Sequence clustering
      was obtained corresponding to the traditional classification based on similarity
      of biochemical, biological and parasitological characteristics of these
      Leishmania species, distinguishing the Old World dermotropic leishmanias, the New
      World dermotropic leishmanias of the sub-genus Leishmania and of the sub-genus
      Viannia.

PMID- 9040847
TI  - Biological comparison between three clones of Trypanosoma cruzi and the strain of
      origin (Bolivia) with reference to clonal evolution studies.
AB  - After isolating three clones of Trypanosoma cruzi (Bolivia), we first
      characterized them according to parasitaemia, pleomorphism and virulence, and
      then histopathologically. The study's interest lies on the hypothesis that clonal
      evolution of T. cruzi has a major impact on biologically relevant properties of
      this parasite. Data obtained from the studies of parasitaemia, pleomorphism and
      virulence showed no differences between the groups studied. As a final point, the
      histopathological study shows us a muscular tissue tropism both in clones and in
      their mother strain (Bolivia). In this paper, we conclude that Bolivia strain and
      clones isolated from it, pertaining to the same major clone share similar
      biological properties.

PMID- 9040848
TI  - The associated microflora to the larvae of human bot fly Dermatobia hominis L.
      Jr. (Diptera: Cuterebridae) and its furuncular lesions in cattle.
AB  - The microflora associated to furuncular lesions, larvae and pupae of Dermatobia
      hominis, as well as the relationships between parasite, host and microflora
      associated, as a comprehensive microsystem, has been studied. One hundred and two
      furuncular myiasis due to D. hominis larvae in several breeds of cattle were
      studied and the following bacterial species were significant: Staphylococcus
      aureus, S. epidermidis, S. warneri, Bacillus subtilis and Escherichia coli.
      Closely related, the microflora associated to 141 samples from first, second,
      third instar larva and both external surface and larval cavities has been
      studied. The representative associated microflora to the larvae were: S. aureus,
      B. subtilis, S. hycus and Moraxella phenylpiruvica, Moerella wisconsiensis,
      Proteus mirabilis and P. vulgaris, M. phenylpiruvica, M. wisconsiensis, P.
      mirabilis and P. rettgeri were the representative microflora associated to 64
      pupae of D. hominis.

PMID- 9040849
TI  - Report of the First Brazilian Symposium on Basic Research in HIV/AIDS.

PMID- 9040850
TI  - A nationwide effort to sistematically monitor HIV-1 diversity in Brazil:
      preliminary results. Brazilian Network for the HIV-1 Isolation and
      Characterization.

PMID- 9040851
TI  - Polymorphism of the predictive antigenic sites on the V3 loop of Brazilian HIV-1
      subtype B strains. HEC/FIOCRUZ AIDS Clinical Research Group.

PMID- 9040852
TI  - Neutralization of primary HIV-1 isolated from individuals residing in Rio de
      Janeiro. HEC/FIOCRUZ AIDS Clinical Research Group.

PMID- 9040853
TI  - Immunoreactivity of Brazilian HIV isolates with different V3 motifs.

PMID- 9040854
TI  - In vitro transfer of cellular immunity to synthetic peptides of HIV-1 to human
      lymphocytes with exogenous RNA.

PMID- 9040855
TI  - Dried blood spots collected on filter paper: an international resource for the
      diagnosis and genetic characterization of human immunodeficiency virus type-1.
AB  - The collection of dried blood spots (DBS) on filter paper provides a powerful
      approach for the development of large-scale, population-based screening programs.
      DBS methods are particularly valuable in developing countries and isolated rural
      regions where resources are limited. Large numbers of field specimens can be
      economically collected and shipped to centralized reference laboratories for
      genetic and (or) serological analysis. Alternatively, the dried blood can be
      stored and used as an archival resource to rapidly establish the frequency and
      distribution of newly recognized mutations, confirm patient identity or track the
      origins and emergence of newly identified pathogens. In this report, we describe
      how PCR-based technologies are beginning to interface with international
      screening programmes for the diagnosis and genetic characterization of human
      immunodeficiency virus type 1 (HIV-1). In particular, we review recent progress
      using DBS specimens to resolve the HIV-1 infection status of neonates, monitor
      the genetic evolution of HIV-1 during early infancy and establish a sentinel
      surveillance system for the systematic monitoring of HIV-1 genetic variation in
      Asia.

PMID- 9040856
TI  - Laboratory indicators for monitoring HIV disease.
AB  - Immunological monitoring of disease progression following HIV infection and
      seroconversion illness, latency and AIDS, not only helps in the basic
      investigation of the natural history of the viral infection in man, but also can
      assist in prognosis and treatment of AIDS-defining illnesses. However, outside
      clinical trials, these tests should be selected and used in clinical practice
      only if they are validated as relevant and effective. The absolute CD4+ T-helper
      lymphocyte count, measured by flow cytometry, has emerged as the best available
      investigation, but needs care in sampling due to diurnal and circadian rhythms,
      effects of age, pregnancy, therapy, intercurrent infections and technique.
      Sampling should provide a baseline and trends-monthly intervals initially, then
      quarterly in uncomplicated cases. Thresholds may be given for counts (e.g.
      200/microliter) below which prophylaxis against pneumocystis pneumonia should be
      administered, and repeating persistently low counts (e.g. below 50/microliter) is
      seldom helpful in practice. Serum levels of beta-2 microglobulin, neopterin and
      immunoglobulins rarely add information. Physicians and laboratories should have
      testing guidelines based on clinical audit of best practice, based in turn on
      scientific understanding of the immunological processes involved.

PMID- 9040857
TI  - Gastrointestinal immune responses in HIV infected subjects.
AB  - The gut associated lymphoid tissue is responsible for specific responses to
      intestinal antigens. During HIV infection, mucosal immune deficiency may account
      for the gastrointestinal infections. In this review we describe the humoral and
      cellular mucosal immune responses in normal and HIV-infected subjects.

PMID- 9040858
TI  - Mucosal immunology and models of mucosal HIV infection.
AB  - The mucosa associated lymphoid tissue regulates and coordinates immune responses
      against mucosal pathogens. Mucosal tissues are the major targets exposed to HIV
      during transmission. In this paper we describe in vitro models of HIV mucosal
      infection using human explants to investigate target cells within this tissue.

PMID- 9040859
TI  - Spectrum of morphologic changes of lymph nodes in HIV infection.
AB  - Cervical lymph nodes biopsies from 31 HIV positive patients (with or without
      AIDS) were studied by histologic methods and immunohistochemistry (StreptABC
      staining of paraffin sections) to identify cellular and extracellular matrix
      components. The results were the following: (1) the biopsies were included in the
      stages of follicular hyperplasia without fragmentation FH-FF (4 cases);
      follicular hyperplasia with follicular fragmentation FH + FF (16 cases);
      follicular involution FI (6 cases) and diffuse pattern DP (5 cases); (2) the most
      important alteration was the germinal centers disruption due to follicle lysis,
      which began in the light zone; (3) there was coincidence between intrafollicular
      hemorrhages and segmental hyaline mycroangiopathy; (4) during the progression of
      the disease occurred; (a) an increase in the number of mast cells, CD68+ and Mac
      387+ macrophages; (b) a diffuse augment of collagen III, elastic fibers, laminin,
      fibronectin and proteoglycans; (c) maintenance of Factor VIII-related antigens in
      the vascular endothelial cells, with decrease in the expression of Ulex-Europeus
      I lectin. Follicular hyperplasia (FH - FF or FH + FF) was the most common
      histologic pattern recognized in the lymph nodes of patients without AIDS and
      follicular involution and difuse pattern were seen in those who had AIDS. The
      results indicate that the lymph node biopsies may provide important information
      about the evolutive stage of the disease and its prognosis.

PMID- 9040860
TI  - CD4+ and CD8+ T cell immune responses of immunocompetent and immunocompromised
      (AIDS) patients with American tegumentary leishmaniasis.

PMID- 9040861
TI  - Co-infection with HIV and Mycobacterium tuberculosis: immunologic interactions,
      disease progression, and survival.

PMID- 9040863
TI  - Mixture distribution and receiver operating characteristic analysis of bedside
      chest imaging with screen-film and computed radiography.
AB  - RATIONALE AND OBJECTIVES: The authors demonstrated the use of mixture
      distribution analysis as an alternative to receiver operating characteristic
      (ROC) analysis in a clinical study, where independent verification of the imaging
      diagnosis is not always feasible. METHODS: ROC and mixture distribution analyses
      were applied to the blind readings of four radiologists on a stratified, random
      sample of 95 screen-film radiographs and 95 computed radiographs of the chest
      obtained from a medical intensive care unit. The imaging diagnosis established by
      an expert panel was used as the truth for the ROC analysis, and agreement of
      ratings was used for the mixture distribution analysis. RESULTS: Both methods
      yielded similar values for the proportion of correct diagnoses. CONCLUSION:
      Mixture distribution analysis may be useful for comparing imaging techniques in
      situations where the true imaging diagnosis cannot be established with a method
      independent of that being evaluated.

PMID- 9040864
TI  - Detection of breast cancer at a smaller size can reduce the likelihood of
      metastatic spread: a quantitative analysis.
AB  - RATIONALE AND OBJECTIVES: The authors extrapolated the lognormal relationship
      between size of tumor and probability of metastasis to include small tumors.
      METHODS: Extrapolation was performed by using linear weighted regression analysis
      techniques to estimate prediction intervals for the predicted probabilities.
      RESULTS: Tumors detected at 1 cm in diameter had a 7.31% probability of
      metastasis (95% prediction interval [PI], 4.36% to 11.6%). Tumors detected at 5
      mm in diameter had a 1.23% probability of metastasis (95% PI, 0.45% to 3.0%).
      Tumors detected at 2 mm had a 0.049% probability of metastasis (95% PI, 0.00705%
      to 0.267%). CONCLUSION: This analysis shows a major reduction in metastasis
      probability when tumors are detected at small sizes. These results suggest that
      detection of very early tumors can substantially reduce the likelihood of
      metastatic spread.

PMID- 9040862
TI  - Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis
      patients: evidence for new recruitment and cell activation.
AB  - Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The
      mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by
      which the microbe evades control to cause disease remain poorly understood. As an
      initial effort to delineate these mechanisms, we examined by immunostaining the
      phenotype of mononuclear phagocytes obtained from lungs of patients with active
      tuberculosis. From August 1994 to March 1995, consecutive patients who had an
      abnormal chest X-ray, no demonstrable acid-fast bacilli in sputum specimens and
      required a diagnostic bronchoalveolar lavage (BAL) were enrolled. Of the 39
      patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of
      the 21 tuberculosis patients were either HIV seronegative (n = 12) or had no risk
      factor for HIV and constituted the tuberculosis group. For comparison, M.
      tuberculosis negative patients who had BAL samples taken during this time (n = 9)
      or normal healthy volunteers (n = 3) served as control group. Compared to the
      control group, the tuberculosis group had significantly higher proportion of
      cells expressing markers of young monocytes (UCHM1) and RFD7, a marker for
      phagocytic cells, and increased expression of HLA-DR, a marker of cell
      activation. In addition, tuberculosis group had significantly higher proportion
      of cells expressing dendritic cell marker (RFD1) and epithelioid cell marker
      (RFD9). These data suggest that despite recruitment of monocytes probably from
      the peripheral blood and local cell activation, host defense of the resident lung
      cells is insufficient to control M. tuberculosis.

PMID- 9040865
TI  - Splenic blood flow: evaluation with computed tomography.
AB  - RATIONALE AND OBJECTIVES: To study splenic perfusion with use of computed
      tomography (CT). METHODS: Twenty-six control patients without splenoportal
      disease, six with cirrhosis, and seven with other splenic disease were examined
      with electron-beam CT. Twenty-five milliliters of iohexol (300 mg of iodine per
      milliliter) was given intravenously at 10 mL/sec followed by a saline bolus.
      Multiple single-level axial sections were acquired 8-90 seconds after injection.
      Perfusion was calculated by dividing maximal splenic enhancement by the area
      under the circulation-corrected aortic time-enhancement curve. Subjective
      assessments of enhancement heterogeneity were made, and regional perfusion was
      calculated in 10 patients with heterogeneous enhancement. Total splenic volume
      and blood flow were computed in 21 patients. RESULTS: Mean perfusion (controls:
      1.29 mL/min/mL, miscellaneous group: 1.07 mL/min/mL) was close to predictions.
      There was a trend toward lower perfusion in cirrhotic patients (0.87 mL/min/mL),
      but the difference was not statistically significant. Total splenic blood was
      increased in patients with cirrhosis (P < .01). Marked perfusion heterogeneity
      was observed in 41% of spleens, but by 2 minutes splenic enhancement was uniform.
      CONCLUSION: CT shows promise in the study of splenic blood flow.

PMID- 9040866
TI  - In vivo magnetic resonance evaluation of blood oxygen saturation in the superior
      mesenteric vein as a measure of the degree of acute flow reduction in the
      superior mesenteric artery: findings in a canine model.
AB  - RATIONALE AND OBJECTIVES: The authors tested the hypothesis that changes in
      oxygen saturation (%HbO2) in the superior mesenteric vein (SMV), as measured with
      in vivo magnetic resonance (MR) oximetry, correlate with the degree of acute
      superior mesenteric artery (SMA) flow reduction. METHODS: Ten mongrel dogs were
      studied. A catheter was inserted into the SMV, and a perivascular ultrasonic flow
      probe and an adjustable mechanical occluder were placed around the SMA. MR
      oximetry was carried out at the resting state and after the SMA was constricted
      to predetermined levels (0%-75% of initial flow). In seven dogs, SMV blood
      samples were obtained immediately before and after each MR measurement; %HbO2 was
      measured simultaneously by using an oximeter. With linear regression analysis,
      the SMV %HbO2 measurements obtained at MR imaging were compared with those
      obtained at oximetry. With a logistic model, MR imaging changes in SMV %HbO2 were
      compared with the degree of SMA flow reduction. RESULTS: SMV %HbO2 measurements
      obtained with MR imaging correlated well with those obtained with oximetry (r =
      .97). Changes in SMV %HbO2 measured at MR imaging also correlated well with the
      degree of SMA flow reduction, as determined with a logistic model (P = .01).
      CONCLUSION: Noninvasive in vivo MR measurements of SMV %HbO2 can be used to
      determine the degree of acute SMA flow reduction with a high degree of accuracy
      in a canine model.

PMID- 9040867
TI  - Dynamic phosphorus-31 spectroscopy after fructose load in experimental biliary
      liver cirrhosis.
AB  - RATIONALE AND OBJECTIVES: The authors investigated the usefulness of dynamic
      phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of hepatic
      function by studying the effect of a fructose load on a rat model of liver
      cirrhosis. METHODS: In vivo P-31 MR liver spectra of eight rats with bile duct
      ligature and 10 control rats were obtained every 4.6 minutes before and after
      intraperitoneal fructose load (10 mmol per kilogram of body weight). RESULTS: In
      the basal spectra of the experimental group, the phosphomonoester peak was higher
      than in the control group (P = .026). After the fructose load, the
      phosphomonoester peak increase and the inorganic phosphate peak decrease were
      significantly less marked in the experimental group (P = .003). There was a
      linear correlation between the serum level of bilirubin and the phosphomonoester
      increase (r = .61, P < .001). CONCLUSION: Dynamic P-31 MR spectroscopy may be
      useful in the assessment of hepatic function in chronic liver disease.

PMID- 9040868
TI  - Detection of reperfused ischemia of the rat intestine: value of magnetic
      resonance imaging with small-molecular-weight dysprosium and gadolinium chelates.
AB  - RATIONALE AND OBJECTIVES: The authors assessed whether the small-molecular-weight
      magnetic resonance (MR) imaging contrast agents dysprosium
      diethylenetriamepentaacetic acid bismethylamide (sprodiamide injection), which
      enhances T2*, and gadolinium diethylenetriamepentaacetic acid bismethylamide
      (gadodiamide injection), which enhances T1, could improve the detection of
      reperfused ischemia of the rat intestine. METHODS: Eighteen rats were subjected
      to vascular occlusion of the distal ileum for 30 minutes, followed by
      reperfusion. Ten minutes after reperfusion, T1- and T2-weighted spin-echo (SE)
      images were obtained before and after administration of sprodiamide, gadodiamide,
      or both. The same imaging protocol was applied in another group of 18 rats
      subjected to 10 minutes of occlusion and reperfusion. Histologic examination of
      the intestine was performed after MR imaging. RESULTS: Villous injury (ie,
      denudation) was observed in most cases after 30 minutes of occlusion, but not
      after 10 minutes of occlusion. After 30 minutes of occlusion, the superficial
      part of the ischemic intestine was hyperintense to the normal intestine on
      unenhanced T2-weighted images. Administration of sprodiamide improved the
      contrast between the normal and ischemic intestine on T2-weighted images, and
      administration of both gadodiamide and sprodiamide improved the contrast on T1-
      and T2-weighted images. After 10 minutes of occlusion, no contrast was
      discernible before or after contrast material administration. CONCLUSION: These
      results suggest that the detection of reperfused intestinal ischemia of
      sufficient duration to cause villous injury can be improved by using sprodiamide
      injection alone or in combination with gadodiamide.

PMID- 9040869
TI  - Gradient-echo magnetic resonance signal decay in a porcine vertebral body model:
      influence of chemical shift.
AB  - RATIONALE AND OBJECTIVES: This study investigates how magnetic resonance (MR)
      signal and T2* of trabecular bone are affected by chemical shift. METHODS: Five
      pigs were sacrificed, and 150 gradient-echo MR images with increasing echo times
      (TEs) were obtained of the lumbar spine. Two vertebrae were excised, defatted,
      and imaged. Commercial fat-protein emulsions with 40%, 27%, and 15%
      concentrations of fat were studied. Regions of interest in subcutaneous fat (n =
      3), bladder (n = 4), vertebral body (n = 10), and defatted vertebral body (n =
      10) were used to study decay of signal intensity. RESULTS: MR signal intensity of
      the vertebrae decreased with a superimposed modulation. The periodicity was 4.65
      msec (range, 4.60-4.68 msec). At a TE of 0 msec, a phase shift of 24 degrees
      (range, 14 degrees-37 degrees), which corresponds to a shift in TE of 0.31 msec
      at 1.5 T, was present. In the fat-protein emulsions, the amplitude of the
      modulation increased with the amount of fat. CONCLUSION: Chemical shift and the
      amount of fat affects T2* measurements.

PMID- 9040870
TI  - Sampling variability of nonparametric estimates of the areas under receiver
      operating characteristic curves: an update.
AB  - RATIONALE AND OBJECTIVES: Several methods have been proposed for calculating the
      variances and covariances of nonparametric estimates of the area under receiver
      operating characteristic curves (AUC). The authors provide an explanation of the
      relationships between them and illustrate the factors that determine sampling
      variability. METHODS: The authors investigated the algebraic links between two
      methods, that of "placements" and that of "pseudovalues" based on jackknifing.
      They also performed a numerical investigation of the comparative performance of
      the two methods. RESULTS: The "placement" method has a simple structure that
      illustrates the determinants of the sampling variability and does not require
      specialized software. The authors show that the pseudovalues used in the
      jackknife method are directly linked to the placement values. CONCLUSION: Because
      of the close link, borne out in a numeric investigation of the sampling
      variation, and because of the ease of computation, the choice between the two
      methods can be based on users' preferences. For indexes other than the AUC,
      however, the use of pseudovalues holds greater promise.

PMID- 9040871
TI  - Radiology in Australia.

PMID- 9040872
TI  - Achievement of substantial cost reduction through joint purchasing by the
      radiology departments of a large vertically integrated health care system.
AB  - RATIONALE AND OBJECTIVES: The authors sought to lower costs by coordinating the
      purchase of equipment, supplies, and services in the radiology departments of a
      vertically integrated health system formed by the merger of two of the largest
      academic medical centers in New England. METHODS: The radiology departments at
      Massachusetts General Hospital and Brigham & Women's Hospital formed a cost
      reduction task force to explore opportunities to jointly decrease costs. Data
      from the operating budgets of both institutions were collected and analyzed to
      find specific items within the budgets that could yield substantial cost savings.
      RESULTS: The project's first phase yielded over $810,000 in reduced costs from a
      system-wide annual budget of only $7 million for film and contrast material.
      Ongoing additional projects suggest that longer term contracts that contain
      steeper discounts with a decreased number of vendors will result in further
      decreases in the cost of materials and supplies. CONCLUSION: Coordination of
      purchasing by the radiology members of an integrated delivery system can yield
      substantial savings.

PMID- 9040873
TI  - The internal review: simplifying a tedious task.

PMID- 9040874
TI  - Lobulated chest wall masses in an adult male.

PMID- 9040876
TI  - Who is watching the teaching?

PMID- 9040877
TI  - Development of a standardized curriculum for training residents in diagnostic
      radiology.

PMID- 9040878
TI  - The management of rheumatoid nodules.

PMID- 9040879
TI  - Traumatic hip dislocation during childhood.

PMID- 9040880
TI  - Repair of distal humeral malunion in children.

PMID- 9040881
TI  - Pectoralis tendon avulsions.

PMID- 9040882
TI  - Melorheostosis.
AB  - Melorheostosis is a rare, benign connective-tissue disorder characterized by a
      cortical thickening of bone with irregular dense hyperostosis that appears to
      flow along the cortex. We review the literature to date, etiology, clinical
      aspects, roentgenographic features, histology, and treatment of melorheostosis.

PMID- 9040883
TI  - Evaluation of the painful wrist.
AB  - Evaluation of wrist pain begins with a review of findings from a thorough medical
      history, a detailed physical examination, and plain radiographs. If a diagnosis
      is not forthcoming, additional diagnostic studies may be obtained, including
      "special" radiographs, bone scans, arthrograms, arthroscopy, and computed
      tomography and magnetic resonance imaging scans. "Abnormal" findings on these
      additional studies must be correlated with findings from the medical history and
      physical examination.

PMID- 9040884
TI  - The relationship of lumbosacral plexus to the sacrum and the sacroiliac joint.
AB  - The lumbosacral plexus was dissected bilaterally in 20 adult cadavers to define
      the anatomic relationship of the lumbosacral plexus to the sacrum and the
      sacroiliac joint. All results are mean values +/- standard deviation. The length
      of the nerve roots of the lumbosacral plexus gradually decreased from L-4 to S-3
      (from 93.8 +/- 6.9 mm in males and 108.7 +/- 7.7 mm in females at L-4 to 43.7 +/-
      4.3 mm in males and 49.0 +/- 7.6 mm in females at S-3). The angle projected by
      the nerve roots of the lumbosacral plexus with respect to the sagittal plane
      gradually increased from L-4 to S-3 (from 14.3 degrees +/- 3.4 degrees in males
      and 16.7 degrees +/- 4.8 degrees in females at L-4 to 51.8 degrees +/- 9.0
      degrees in males and 57.8 degrees +/- 9.1 degrees in females at S-3). The width
      of the nerve roots of the lumbosacral plexus was greatest at S-1 (9.8 +/- 1.8 mm
      in males, 8.6 +/- 1.5 mm in females). The L-5 nerve root was the thickest in
      males (4.4 +/- 0.5 mm), and the S-1 nerve root was thickest in females (4.3 +/-
      0.4 mm). The lumbosacral trunk was 30.0 +/- 9.0 mm in length in males and 32.0 +/
      6.0 mm in females; 11.4 +/- 1.8 mm wide in males and 11.2 +/- 1.5 mm in females;
      and 4.4 +/- 0.5 mm thick in males and 4.0 +/- 0.6 mm in females. The fifth lumbar
      nerve root and lumbosacral trunk coursed across the sacroiliac at a level 2.0 +/-
      0.2 cm below the pelvic brim and were relatively fixed to the sacral ala with
      fibrous connective tissue.

PMID- 9040885
TI  - Prohibitive failure rate of the total articular replacement arthroplasty at five
      to ten years.
AB  - Five- to 10-year follow-up was obtained on a series of total articular
      replacement arthroplasties performed at a single university-affiliated teaching
      hospital. Eighty arthroplasties were performed on 64 patients. Twelve patients
      (accounting for 14 hip arthroplasties) died. Follow-up was obtained on 62 of the
      66 remaining hips (94%). Thirty-five hips had been revised (56%), 32 for
      acetabular loosening and 3 for femoral loosening, 1 of which led to femoral stem
      fracture. The average time to revision was 72 months (22 to 132 months). The
      revision procedures were extensive in terms of operative time, blood loss, and
      necessity of acetabular bone grafting. Follow-up of the 27 that had not been
      revised averaged 84 months and revealed 1 hip excellent, 5 good, 1 fair, and 20
      poor results. The overall clinical failure rate (revisions plus clinically poor
      results) was 89% (55/62 hips). These results are far inferior to conventional
      total hip replacement, and the extent of the revision procedures indicates that
      this is not a conservative alternative to conventional total hip replacement.

PMID- 9040886
TI  - Direct complications of trochanteric osteotomy in open reduction and internal
      fixation of acetabular fractures.
AB  - Osteotomy of the greater trochanter has been used to enhance exposure, especially
      the dome, in posterior and lateral exposures of the acetabulum. In 55 patients,
      osteotomy of the greater trochanter was performed in connection with open
      reduction and internal fixation of a displaced acetabular fracture. The
      trochanter was reattached by screw fixation. One osteotomy resulted in nonunion,
      and 2 cases showed partial avulsion or migration of the trochanter. Eleven of the
      55 patients (20%) required screw removal from the trochanter. Five patients
      developed complete ankylosis from heterotopic ossification despite indomethacin
      prophylaxis; 1 young man underwent excision. Since this procedure increases the
      complications of fracture management, the inherent risk-to-benefit ratio should
      be evaluated in each patient.

PMID- 9040887
TI  - Total knee arthroplasty for osteoarthritis in hereditary onycho-osteodysplasia
      (nail-patella syndrome): a case report.
AB  - Onycho-osteodysplasia is an unusual disorder that affects bone, fingernails, and
      the kidneys. The knees may be involved with a hypoplastic, dislocated patella,
      and premature osteoarthritis with deformity may develop. The following is a case
      report of a patient with this disorder in which a total knee arthroplasty was
      performed.

PMID- 9040888
TI  - Pyomyositis with toxic shock syndrome presenting as back pain and fever: a case
      report and literature review.
AB  - Pyomyositis is an uncommon cause of musculoskeletal pain in children and
      adolescents living in temperate climates. Toxic shock syndrome is a life
      threatening potential complication of pyomyositis. We report a case of acute
      hematogenous pyomyositis, complicated by toxic shock syndrome, and review the
      pertinent literature.

PMID- 9040890
TI  - Late infection of hand implant after a dental procedure: a case report.
AB  - A 78-year-old woman with a silicone implant in her first carpometacarpal joint
      had acute inflammation and lymphangitis beginning 24 hours after a dental root
      canal procedure. The infection resolved after implant removal and debridement of
      the residual carpometacarpal space. Although this is a rare event, the use of
      prophylactic antibiotics to protect implants in the hand should be reviewed.

PMID- 9040889
TI  - Heterotopic ossification after total knee arthroplasty.
AB  - Heterotopic ossification (HO) is a rare complication following total knee
      arthroplasty (TKA). In the case report presented, a 52-year-old man who had
      previously undergone TKA for osteoarthritis noticed painful limitation of range
      of motion (ROM) in spite of active participation in physical therapy and the use
      of a continuous passive motion machine. A plain radiograph 1 month after surgery
      revealed HO anterior to the distal femoral shaft in the quadriceps expansion.
      Ambulation for this patient was limited to short distances because of severe pain
      and limitation in ROM. The patient underwent manipulation under general
      anesthesia 2 months after the TKA. Range of motion in flexion improved from 50
      degrees to 110 degrees, and the patient became ambulatory without assistive
      devices. However, the flexion range deteriorated to 50 degrees over a period of 4
      months, and ambulation again became significantly limited. The patient underwent
      resection of HO 6 months after manipulation and regained his ROM to 110 degrees
      in flexion. He was prescribed indomethacin after surgery for 2 months to prevent
      recurrence of HO. Follow-up radiographs 3 months after surgery revealed minimal
      recurrence of HO. The patient's ROM did not deteriorate, and he remained
      ambulatory. Heterotopic ossification should be suspected in post-TKA patients if
      ROM does not improve. Physical therapy including ROM exercises remains an
      essential component in the treatment of HO. Manipulation under general anesthesia
      or surgical resection of HO may be inevitable in certain patients whose
      ambulation is significantly limited.

PMID- 9040891
TI  - Repair of rupture of the distal tendon of the biceps brachii. Review of the
      literature and report of three cases treated with a single anterior incision and
      suture anchors.
AB  - Operative repair of distal biceps tendon ruptures is recommended for active
      individuals desiring maximum return of elbow supination and flexion power and
      endurance. Traditional two-incision repair methods are highly successful, but
      they carry the risk of radioulnar synostosis formation if the ulna is exposed.
      Repair via an anterior incision through bone drill holes requires more dissection
      and potential risk to the posterior interosseous nerve. The authors present a
      method of repair of distal biceps tendon ruptures via a single anterior incision
      using suture anchors. This technique has been used in 3 patients with excellent
      functional results and is recommended for use as an alternative to the two
      incision method.

PMID- 9040892
TI  - Factors that affect fracture healing.

PMID- 9040893
TI  - A 63-year-old woman with right small finger pain.
AB  - The following case is presented to illustrate the clinical findings and imaging
      modalities of a condition of interest to the orthopedic/hand surgeon. The initial
      history, physical examination, and imaging examinations are found on this page.
      The final clinical and roentgenographic differential diagnosis and discussion can
      be found on the following pages.

PMID- 9040895
TI  - The GRAIL concept modelling language for medical terminology.
AB  - The GALEN representation and integration language (GRAIL) has been developed to
      support effective clinical user interfaces and extensible re-usable models of
      medical terminology. It has been used successfully to develop the prototype GALEN
      common reference (CORE) model for medical terminology and for a series of
      projects in clinical user interfaces within the GALEN and PEN&PAD projects. GRAIL
      is a description logic or frame language with novel features to support part
      whole and other transitive relations and to support the GALEN modelling style
      aimed at re-use and application independence. GRAIL began as an experimental
      language. However, it has clarified many requirements for an effective knowledge
      representation language for clinical concepts. It still has numerous limitations
      despite its practical successes. The GRAIL experience is expected to form the
      basis for future languages which meet the same requirements but have greater
      expressiveness and more soundly based semantics. This paper provides a
      description and motivation for the GRAIL language and gives examples of the
      modelling paradigm which it supports.

PMID- 9040894
TI  - An evaluation of machine-learning methods for predicting pneumonia mortality.
AB  - This paper describes the application of eight statistical and machine-learning
      methods to derive computer models for predicting mortality of hospital patients
      with pneumonia from their findings at initial presentation. The eight models were
      each constructed based on 9847 patient cases and they were each evaluated on 4352
      additional cases. The primary evaluation metric was the error in predicted
      survival as a function of the fraction of patients predicted to survive. This
      metric is useful in assessing a model's potential to assist a clinician in
      deciding whether to treat a given patient in the hospital or at home. We examined
      the error rates of the models when predicting that a given fraction of patients
      will survive. We examined survival fractions between 0.1 and 0.6. Over this
      range, each model's predictive error rate was within 1% of the error rate of
      every other model. When predicting that approximately 30% of the patients will
      survive, all the models have an error rate of less than 1.5%. The models are
      distinguished more by the number of variables and parameters that they contain
      than by their error rates; these differences suggest which models may be the most
      amenable to future implementation as paper-based guidelines.

PMID- 9040896
TI  - A process-oriented reasoner about physiology.
AB  - This paper presents the RAP system: a reasoner about physiology. RAP performs two
      tasks: (1) it infers the behaviour of a complex physiological process using the
      behaviours of its subprocesses and the relationships between them; (2) it reasons
      about the effect of introducing a fault into the model. In order to reason about
      the behaviour of a complex process, RAP uses a mechanism which: (i) represents
      how subprocesses behave; (ii) establishes how these subprocesses affect each
      others behaviors; (iii) 'aggregates' these behaviors together to obtain the
      behavior of the top level process; (iv) gives that process a temporal context in
      which to act. RAP uses limited common sense knowledge about faults to reason
      about their effect in terms of the generation of new processes and the
      misbehavior of existing ones. The effects are then propagated throughout the
      model to obtain the overall effect of the fault.

PMID- 9040897
TI  - The effect of different types of exercise on gastro-oesophageal reflux.
AB  - Sportsmen and women frequently experience abdominal and chest pain during
      exertion. The symptoms could be cardiac but may be caused by gastro-oesophageal
      reflux (GOR). The aim of our study was to investigate the effect of the two
      activities on GOR in 17 fit, healthy adults. GOR, assessed by intraoesophageal
      pH, was recorded on portable monitoring equipment before, during and after rowing
      and running. GOR was also measured after a light meal to simulate pre-training
      hydration. Three studies were performed: rowing, fasted running, and post
      prandial running. GOR was infrequent before exercise, being seen in only 2
      subjects. However, GOR was induced in 70% of rowers, 45% of fasted runners, and
      90 % of fed runners during and immediately after exercise. The presence of food
      in the stomach greatly increased the amount of reflux during post-prandial
      running, (p < 0.006 against control) but reflux was also significantly higher in
      those who refluxed during fasted running (p < 0.03) and rowing (p < 0.08). There
      was no statistical difference in the amount of GOR between the two exercise
      periods. This study shows that both running and rowing induce significant amounts
      of GOR in a normally asymptomatic group of athletes. GOR should be considered in
      the investigation of exertional chest pain in patients attending a sports clinic.

PMID- 9040898
TI  - The incidence of injury in surfboat rowers.
AB  - A questionnaire was completed by 202 surfboat rowers. The questionnaire
      investigated injuries that occurred over the preceding two years. The injuries
      were classified according to the nature of onset of the injury, the anatomical
      location of the injury, and the age of the rower. Eighty percent of surfboat
      rowers reported some type of injury during the two years prior to completing the
      questionnaire. Eighty one percent of injuries were classified as chronic
      insidious onset injuries. The mean time lost from employment due to chronic
      insidious onset injuries was 10.4 days, Low back pain accounted for 60% of all
      injuries. Sixty percent of the acute injuries were hamstring or calf tears that
      were incurred during sprint running training. No relationship between age or
      surfboat rowing experience and incidence of injury was identified. The present
      study suggests that there is a high incidence of injury in surfboat rowing, and
      that most injuries are chronic injuries and are of an insidious onset.

PMID- 9040899
TI  - The influence of resistance training on the critical power function & time to
      fatigue at critical power.
AB  - The present study examined whether a six-week resistance training program would
      influence the critical power (CP) function, time to exhaustion (TE) at CP and/or
      peak oxygen uptake (VO2 peak). The CP function is believed to provide an index of
      endurance ability (CP given by the slope), and anaerobic work capacity (the y
      intercept). Eight healthy, untrained males undertook lower-body resistance
      training (90 min/day, 3-4 times/wk) for six weeks; eight controls refrained from
      resistance or endurance training for the same period. Before and immediately
      following the training period, subjects completed three trials to determine their
      CP function, a test of VO2 peak, a one-repetition maximum (1-RM) leg press test
      and TE at their CP. Training significantly increased both 1-RM leg press (28.6%,
      P < 0.05) and the y-intercept (34.9%, P < 0.05) while no changes in CP, VO2 peak
      or TE (p > 0.05) were found. Changes in the y-intercept following resistance
      training were negatively correlated with changes in the CP (r = -0.94, p < 0.05,
      N = 8). The present data show that the y-intercept of the CP function is
      sensitive to, and modified by, six weeks of resistance training. Given that
      resistance training had no significant influence on CP, TE at CP or VO2 peak, the
      present study has also shown that six weeks of resistance training will not alter
      indices of endurance ability. The negative relationship between changes in the y
      intercept and CP exposes a potential limitation of the linear CP function when
      evaluating changes in endurance ability following an intervention which
      significantly alters the y-intercept.

PMID- 9040900
TI  - The role of upper limb segment rotations in the development of spin in the tennis
      forehand.
AB  - Increased topspin in the tennis forehand is produced by maintaining a
      perpendicular racket-face to the court surface at impact and increasing the
      trajectory and vertical velocity of the racket-head. These modifications to
      stroke technique from those previously identified in the flat forehand drive are
      the result of changes to the movement patterns of the segments of the upper limb.
      The contributions that the upper limb segment's anatomical rotations make to
      racket-head velocity at impact depend on both their angular velocity and the
      instantaneous position of the racket with respect to these movements. Six high
      performance tennis players were filmed at a nominal rate of 200 Hz by three
      Photosonics cameras while hitting flat (no spin) and topspin groundstrokes and a
      forehand topspin lob. The three-dimensional (3-D) displacement histories of 16
      selected landmarks were then calculated using the direct linear transformation
      approach and 3-D individual segment rotations for the upper limb were calculated
      using vector equations. Significant differences were recorded in the effect that
      the various segment rotations made to the x-direction (forward) and y-direction
      (upward) impact velocities of the racket-head. These differences were not
      reflected in the contributions to racket-head velocity when the absolute
      velocities were expressed relative to the impact velocity. Trunk rotation, upper
      arm flexion/abduction, upper arm internal rotation, hand palmar and ulnar flexion
      all played integral roles in producing impact racket speed.

PMID- 9040901
TI  - Heart rate response and perceived exertion during twenty consecutive karate
      sparring matches.
AB  - This study investigated the changes in heart rate (HR) and perceived exertion
      ratings (RPE) of 20 consecutive karate sparring matches each of 2 minutes
      duration. The resting and maximal HR (HRmax) responses to the maximal treadmill
      test were 69.8 +/- 2.9 beats.min-1 and 198.5 +/- 8.2 beats.min-1, respectively.
      The resting HR before the 20 sparring matches was 83.5 +/- 11.3 beats min-1. The
      mean HR during the 20 sparring matches was 191.8 +/- 9.4 beats.min-1 which was
      equal to 96.7 +/- 4.2% of HRmax. At the end of the 20 sparring matches, the mean
      RPE obtained was 19 +/- 2. The results of this study suggest that the subjects
      could continue the 20 sparring matches for about 40 minutes at the intensity
      close to the HRmax.

PMID- 9040902
TI  - Euthanasia and physician-assisted suicide. The wrong issues in the care of dying
      people.

PMID- 9040903
TI  - Lobbying the lawmakers. The college and assisted death.

PMID- 9040904
TI  - The importance of being different. Part 1: The marginal status of family
      medicine.

PMID- 9040905
TI  - Dehydration in the terminally ill.

PMID- 9040906
TI  - How to ensure fetal safety when mothers use isotretinoin (Accutane).

PMID- 9040907
TI  - Ophthaproblem. Macular degeneration.

PMID- 9040908
TI  - Dermacase. Bullous pemphigoid.

PMID- 9040909
TI  - Up your nose. Quick and somewhat dirty method of removing foreign bodies from
      children's noses.

PMID- 9040910
TI  - Euthanasia in family practice in The Netherlands. Toward a better understanding.
AB  - OBJECTIVE: To describe the incidence of euthanasia and assisted suicide in family
      practice in the Netherlands, the reasons for its practice, and the
      characteristics of patients and physicians involved. DESIGN: Cross-sectional
      survey of a random sample of Dutch family physicians. SETTING: General practices
      in The Netherlands. PARTICIPANTS: An anonymous questionnaire was mailed to 1042
      general practitioners. Of the 996 eligible physicians, 667 (67%) completed the
      questionnaire. MAIN OUTCOME MEASURES: Reported practices and beliefs concerning
      euthanasia and assisted suicide. RESULTS: In the course of an average year, 24%
      of Dutch family physicians had practised euthanasia or assisted suicide. Most
      deaths took place at home in the presence of others. According to the physicians,
      the most important reasons for the request were futile suffering, fear or
      avoidance of loss of dignity, and unbearable suffering. Euthanasia or assisted
      suicide was mostly (85%) administered to patients with malignant neoplasms.
      Physicians were more opposed to euthanasia and assisted suicide if they had never
      practised it, if they had a religious affiliation, and if they were older.
      CONCLUSIONS: This study presents empiric data about euthanasia and assisted
      suicide in the context of a permissive euthanasia policy. Understanding Dutch
      practices could be helpful for Canadians. However, each country needs to resolve
      these issues in its own way.

PMID- 9040911
TI  - Attitudes toward obstetrics training. Residents surveyed at McGill University and
      University of Montreal.
AB  - OBJECTIVE: To determine family medicine residents' attitudes toward family
      practice training in obstetrics and neonatology before and after implementation
      of a modified obstetrics curriculum at McGill University (MG). DESIGN: Two-group
      pretest and posttest. Fifty-seven respondents, 31 at MG, 26 at University of
      Montreal (UM), were case matched as first-year and second-year residents.
      SETTING: Departments of Family Medicine at MG and UM. PARTICIPANTS: Family
      medicine residents at MG and UM. INTERVENTION: A modified obstetrics curriculum
      was introduced at MG (study group); no modifications were introduced at UM
      (control group). First- and second-year residents' attitudes toward the adequacy
      of training were assessed through responses to a questionnaire administered in
      July 1992 and July 1994. MAIN OUTCOME MEASURES: Changes in response scores before
      and after implementation of the modified curriculum. RESULTS: Repeated
      multivariate analysis of variance (MANOVA) showed respondents believed family
      practice obstetrics training was adequate in general, but that family
      practitioners were inadequately trained in emergency obstetric skills. Scores for
      items assessing neonatology skills increased significantly in the MG group after
      the intervention. CONCLUSIONS: Residents' overall confidence in their obstetrics
      training did not appear to improve, but this might be due to a time lag between
      curriculum modification and attitudinal change. McGill residents' confidence in
      neonatology skills improved significantly after curriculum modification.

PMID- 9040912
TI  - Family physicians and the mental health system. Report from the Mental Health
      Supplement to the Ontario Health Survey.
AB  - OBJECTIVE: To determine family physicians' role in the mental health care system.
      DESIGN: The Mental Health Supplement to the Ontario Health Survey is an
      epidemiologic, retrospective, home-interview survey. Results reported here are
      based on responses of a weighted sample of patients aged 15 to 64. SETTING:
      Ontario, 1990 to 1991. PARTICIPANTS: Random sample of 9953 household residents.
      MAIN OUTCOME MEASURES: Standardized assessment of mental disorders, associated
      risk factors and disability, and patterns of use of mental health services.
      RESULTS: More people seek mental health services from their family physicians
      (FPs) than from psychiatrists, social workers, or psychologists. Among patients
      who consulted for mental health purposes, more than 35.4% saw FPs only, 24.7% saw
      FPs and other mental health care providers (psychiatrists, psychologists, social
      workers, others), and 40% saw other mental health care providers only. There were
      few sociodemographic, diagnostic, or clinical severity differences between the FP
      only group and the other two groups. Some evidence suggested FPs saw more recent
      onset cases, but they were also involved in joint care for more complex or
      disabled cases. More than 57% of those seeing FPs received medication; 43%
      received other forms of care. Those seeing FPs only made four visits per year;
      those who consulted other mental health professionals made 14 to 20. CONCLUSIONS:
      Our study confirms FPs' important role in the current mental health care system.

PMID- 9040913
TI  - Medical management of intestinal obstruction in terminal care.
AB  - OBJECTIVE: To review the evidence on the effectiveness of medical management of
      bowel obstruction for patients with advanced cancer and to summarize treatment
      options for home and hospital care. DATA SOURCES: Articles were identified by
      searching MEDLINE. STUDY SELECTION: Research articles published between 1973 and
      1995 on the surgical and medical management of bowel obstruction in patients with
      advanced cancer were identified. Seven original research articles on medical
      management were identified and all were reviewed and critically appraised. Given
      the small number of original papers in this field, studies using prospective and
      retrospective methodology were included. Articles looking only at the use of
      percutaneous gastrostomy tubes and subcutaneous hydration were used in the
      formulation of treatment recommendations but were not critically reviewed. A
      critical appraisal of the surgical literature was not undertaken. SYNTHESIS:
      Recommendations regarding medical management of bowel obstruction were based on
      strength of evidence for improving symptoms with pharmacologic treatment. The few
      clinical trials were uncontrolled trials with small samples. The trials show
      improvement of symptom control with pharmacologic management using morphine,
      anticholinergics, major tranquilizers, corticosteroids, and somatostatin
      analogues. Intravenous hydration was unnecessary for most patients. Percutaneous
      gastrostomy tubes are effective for patients with proximal intestinal obstruction
      and intractable vomiting. CONCLUSIONS: Pharmacologic management and percutaneous
      gastrostomy for intractable vomiting and hypodermoclysis or oral fluids for
      hydration can control symptoms without surgery or nasogastric tubes.

PMID- 9040914
TI  - Fentanyl transdermal system. Pain management at home.
AB  - PROBLEM BEING ADDRESSED: About 65% of patients with advanced malignancies
      experience cancer pain. Although oral opioids provide effective analgesia for
      most of these patients, alternate routes of drug delivery are often necessary as
      the disease progresses. PURPOSE OF PROGRAM: To study use of Duragesic (fentanyl
      transdermal system), the only transdermal opioid approved in Canada for treating
      chronic cancer pain in adults. MAIN COMPONENTS: Transdermal fentanyl was
      prescribed for a heterogeneous group of 44 patients (aged 29 to 82 years) to
      treat cancer pain (37 patients), chronic non-malignant pain (six patients), and
      pain associated with terminal AIDS (one patient), for periods of 2 to 384 days.
      Patients were treated individually and switched to transdermal fentanyl from
      other opioids when oral delivery was no longer possible. Doses were titrated as
      necessary and ranged from 25 micrograms/h to 300 micrograms/h. Incidental pain
      was treated effectively with short-acting opioids. CONCLUSIONS: Eighty percent of
      patients experienced good analgesia, which led to an overall improvement in their
      quality of life. Transdermal fentanyl was discontinued for 17% of patients due to
      intractable nausea, diarrhea, adherence problems, or poor analgesia. Many
      patients wore the system until they died or until a few days before death when
      severe increasing pain necessitated parenteral opioids. The side effects of
      transdermal fentanyl were similar to those of conventional opioids. Patient
      compliance and acceptance of this noninvasive, continuous system of drug delivery
      has been excellent; its simplicity of administration allows patients to be cared
      for at home.

PMID- 9040915
TI  - Integrating family medicine residents into a rural practice.
AB  - PROBLEM: Integrating residents into community family practices can be challenging
      for busy doctors, especially when new preceptors have no formal preparation or
      teaching experience. OBJECTIVE OF PROGRAM: To develop an organized and practical
      approach to teaching residents in our busy rural group practice. Our seven
      northern Ontario family doctors have been training elective residents and clerks
      for 15 years. Recently, we have gone from hosting elective residents and students
      to teaching core family medicine residents. Our precepting plan allows us to
      dedicate a reasonable time to teaching while fulfilling our primary care duties.
      MAIN COMPONENTS: The program involves contracting, teaching, monitoring,
      feedback, and evaluation. CONCLUSION: We think we have developed a sustainable,
      workable set of teaching parameters that is applicable by various preceptors in
      different settings. It has simplified our teaching role and lessened our
      anxieties. Residents have benefited from the consistent protocol, which can be
      flexible enough to adapt to individual residents and preceptors, and have valued
      this teaching approach.

PMID- 9040917
TI  - Treatment programs for batterers.

PMID- 9040916
TI  - Onychomycosis. Going for cure.
AB  - OBJECTIVE: To review onychomycosis with an emphasis on the traditional and newer
      antifungal agents available to treat onychomycosis. QUALITY OF EVIDENCE: We
      searched MEDLINE for the years 1966 to 1995. We excluded case reports from our
      analysis. MAIN FINDINGS: For treating onychomycosis, newer antifungal agents
      (such as terbinafine, itraconazole, and fluconazole) are more cost-effective than
      the traditional agents griseofulvin and ketoconazole. Of the newer agents, only
      terbinafine is currently approved in Canada for treating onychomycosis.
      CONCLUSIONS: The new generation of drugs is an important addition to the
      armamentarium of therapies available for treating onychomycosis. At the moment,
      in Canada, terbinafine is the drug of choice and more cost-effective than
      griseofulvin for treating dermatophyte-induced onychomycosis.

PMID- 9040918
TI  - Living with accelerating speed of change.

PMID- 9040919
TI  - The "marriage bed": brain and outcome in schizophrenia.

PMID- 9040920
TI  - The role of the thalamus in schizophrenia.
AB  - BACKGROUND: Explaining the diversity of symptoms that occur in schizophrenia is a
      major conceptual challenge. Perhaps the most powerful strategy is to identify a
      fundamental cognitive process and/or a fundamental neural circuit. METHODS:
      Convergent data from our research group in Iowa and from investigators in other
      centres are summarized. RESULTS: The thalamus plays a key role in information
      processing. A defect in circuitry connecting the thalamus, frontal cortex, and
      cerebellum could explain a wide range of symptoms. Neuropathology and imaging
      studies suggest that patients with schizophrenia may have abnormalities in this
      circuitry. CONCLUSION: The fundamental deficit in schizophrenia may be
      conceptualized as a "cognitive dysmetria" characterized by impairments in
      coordinating the perception, encoding, retrieval, and prioritization of
      experience and information.

PMID- 9040921
TI  - The varied outcomes of schizophrenia.
AB  - OBJECTIVE: To review variations in outcomes in schizophrenia across individual,
      historical, and cross-cultural boundaries, as well as within specific domains of
      functioning. METHOD: Research literature on the outcomes of schizophrenia
      appearing within the last 8 years was reviewed. RESULTS: First, a review of
      follow-up studies published in the developed world suggests that heterogeneity in
      outcome across individuals with schizophrenia remains the rule, with affective
      symptoms, later and acute onset, and responsiveness to biological treatments
      predictive of good outcome. Negative symptoms are associated with poor outcome,
      cognitive impairments, and incapacity in social and work domains. Deterioration
      appears to occur within the first few months of onset if not already in the
      prodrome, with recent early-course studies finding longer duration of untreated
      psychosis associated with insidious onset, negative symptoms, social and work
      incapacity, and poor outcome. Second, a review of recent cross-cultural and
      historical studies provides evidence that outcome varies across time and place,
      schizophrenia having a more favourable outcome in the developing world and
      becoming a more benign disorder over the course of this century. Third, a review
      of studies of the domains of functioning within individuals identifies 4
      relatively independent dimensions of depression and negative, psychotic, and
      disorganized symptoms. Cognitive deficits, which are associated with negative
      symptoms, also constitute a relatively stable dimension over time, showing
      neither marked deterioration nor improvement once established early in the course
      of disorder. CONCLUSIONS: The early appearance and stability over time of
      negative symptoms and cognitive impairments call for assertive intervention
      efforts early in the course of disorder to prevent chronicity and prolonged
      disability.

PMID- 9040922
TI  - Shadows of the truth in patients with spinal pain: a review.
AB  - OBJECTIVE: Spinal pain with or without referred pain is a major and costly health
      problem that can arise from many anatomical structures. Sophisticated diagnostic
      imaging devices cannot show some of these structures, and frequently imaging
      provides only a shadow of the truth. This review illustrates how symptoms may
      well have an organic cause that is not detectable by current methods of
      examination, including imaging. METHOD: This study reviews some histopathological
      findings that can be associated with spinal pain with or without referred pain
      but cannot be seen on imaging. RESULT: Some histopathological changes illustrate
      imaging device limitations. CONCLUSION: Awareness of the considerable limitations
      of even sophisticated imaging devices is necessary when managing patients with
      acute or chronic spinal pain with or without referred pain. Symptoms may well be
      genuine and not of psychogenic origin: a diagnosis of malingering, therefore,
      should not be made lightly.

PMID- 9040924
TI  - Neuroleptic dosing in chronic schizophrenia: a 10-year follow-up.
AB  - OBJECTIVE: To evaluate neuroleptic dosing patterns in individuals with
      schizophrenia over a 10-year interval. METHOD: Changes in neuroleptic dosing
      between 1980 and 1990 were followed in 65 patients with a diagnosis of chronic
      schizophrenia. RESULTS: According to more recent dosing guidelines, doses were
      already high at the time of initial evaluation, yet overall they continued to
      increase during the next decade of treatment for both males and females. Patients
      were almost equally divided, however, by those who underwent an increase (n = 33)
      and those whose dose remained stable (n = 4) or was decreased (n = 28).
      CONCLUSION: A considerable number of patients with schizophrenia appear to
      receive progressively higher neuroleptic doses over the course of their illness,
      despite a lack of empirical data to support such an approach. Results are
      discussed in terms of current dosing recommendations and factors influencing dose
      changes.

PMID- 9040923
TI  - Readiness to stop smoking in schizophrenia.
AB  - OBJECTIVE: To assess the motivation and readiness to change of individuals with
      schizophrenia prior to developing a smoking cessation program. METHOD: Smoking
      history, nicotine dependence, readiness to stop smoking, and interest in a
      smoking cessation group were assessed in 60 schizophrenia outpatients who smoked.
      RESULTS: The majority were interested in attending a smoking cessation group and
      appeared to be appropriately motivated. CONCLUSIONS: Smoking cessation groups for
      a schizophrenia population may be a worthwhile endeavour. Current measures of
      motivation and readiness to change may be useful to identify those who are most
      likely to succeed.

PMID- 9040925
TI  - Rediscovering general psychiatry: creation of an academic division.
AB  - OBJECTIVE: To describe the rationale, origins, and goals of a newly created
      academic division of general psychiatry within a university setting. METHOD:
      Literature review, observation, and description. RESULTS: Within 2 years of its
      inception, the General Psychiatry Division of the University of Toronto has begun
      to realize some of its goals and further elucidate specific objectives.
      CONCLUSIONS: In an era of increasing academic subspecialization, the preservation
      of core skills in psychiatry and the recognition of the continuing public need
      for psychiatric generalists must be enshrined within academic training programs.

PMID- 9040926
TI  - Childhood antecedents of self-destructiveness in borderline personality disorder.
AB  - OBJECTIVE: To assess the relationship between lifetime patterns of self
      destructive behaviour and various parameters of childhood abuse and neglect in
      patients with borderline personality disorder (BPD) compared with other
      personality disorder (OPD) controls. METHOD: The subjects were 42 inpatients with
      the diagnosis of BPD and 17 OPD controls. Lifetime patterns of self-destructive
      behaviour were assessed using the Lifetime Borderline Symptom Index. Childhood
      experiences were assessed using a semistructured interview by raters who were
      blind to diagnosis. RESULTS: Chronic self-destructive behaviour discriminated
      patients with BPD from OPD controls. In the borderline group, parental sexual
      abuse was significantly related to suicidal behaviour and both parental sexual
      abuse and emotional neglect were significantly related to self-mutilation.
      CONCLUSION: Both parental sexual abuse and emotional neglect appear to play a
      role in the etiology of self-destructive behaviour in BPD. The results highlight
      the importance of considering the effects of sexual abuse within its
      environmental context and suggest that the etiology of borderline symptoms is
      likely multifactorial.

PMID- 9040927
TI  - Who applies to regional review boards and what are the outcomes?
AB  - OBJECTIVE: To determine the outcomes for patients following applications to
      regional review boards at an Ontario provincial psychiatric hospital for 1992
      through 1994. METHOD: A retrospective casenote study examined frequency of
      readmission, time to next admission, status upon readmission, and episodes of
      dangerous behaviour perpetrated in the community for patients applying to review
      boards. RESULTS: Over 3 years, 116 hearings took place to review various
      certificates. Only 57% of applications reached a hearing. Of those, 69% were
      confirmed and 31% rescinded. A small group of patients made multiple applications
      to the review board. Median time to next admission for patients who had
      certificates of involuntary admission rescinded by the review board was 14 days,
      compared with 53 days for those who remained in hospital until the time of
      planned discharge. CONCLUSION: Review boards consume considerable resources,
      serve only a small proportion of patients, and contribute to the "revolving door"
      phenomenon.

PMID- 9040928
TI  - Reducing the length of stay in a psychiatric inpatient unit and providing
      community care as an alternative.

PMID- 9040929
TI  - Does combined neuroleptic-electroconvulsive therapy treatment increase the
      likelihood of creatine phosphokinase rise?

PMID- 9040930
TI  - Risperidone treatment of bipolar disorder.

PMID- 9040931
TI  - The antichrist delusion as a delusional misidentification syndrome of the self.

PMID- 9040932
TI  - Clozapine treatment of psychosis associated with multiple sclerosis.

PMID- 9040933
TI  - Venlafaxine and ecchymosis.

PMID- 9040934
TI  - Decreased immunoglobulin deposition in tumors and increased immature B cells in
      p53-null mice.
AB  - Recent studies have hinted that there may be a relationship between p53 and the
      immune response. In preliminary experiments, we found significantly decreased
      levels of immunoglobulin deposition in 13 of 16 p53-null tumors compared with 2
      of 17 tumors derived from p53 +/- mice. We further explored the effect of p53 on
      B-cell development and function. p53-null mice contained more splenic white pulp
      and more immature B cells in the bone marrow compared with p53 +/- mice. p53-null
      B cells were hyperresponsive to proliferative challenge but were not more
      resistant to signal-induced apoptosis. Several p53 DNA-binding sites were
      localized to the regulatory regions of immunoglobulin heavy and light chain
      genes, including the KII site, which serves as an enhancer for rearrangement of
      the mouse kappa chain J cluster genes. Levels of p53 protein and the kappa chain
      sterile transcript increased after exposure of pre-B cells to the DNA damaging
      agents etoposide and Adriamycin. Our observations suggest that p53 may be
      involved in B-cell maturation and may relay certain stress signals to affect B
      cell function.

PMID- 9040935
TI  - Differential regulation of the Wilms' tumor gene, WT1, during differentiation of
      embryonal carcinoma and embryonic stem cells.
AB  - The expression pattern of the Wilms' tumor suppressor gene, WT1, during embryonal
      development suggests a role for the WT1 proteins in the differentiation of
      specific tissues. This notion is supported by the observation that WT1 knock-out
      mice fall to develop kidneys and gonads. We describe here the changes in the
      expression and DNA binding activity of the WT1 gene product in P19 embryonal
      carcinoma cells and embryonic stem cells triggered to differentiate by either
      retinoic acid (RA) or DMSO. In exponentially growing P19 embryonal carcinoma (EC)
      cells, WT1 mRNA and proteins were undetectable. During RA-induced but not DMSO
      induced differentiation of P19 EC cells, WT1 expression and DNA binding are
      strongly activated. Treatment of embryonic stem cells with RA resulted in a
      similar activation of WT1. Immunohistochemical analysis showed that WT1 is
      expressed in endodermal, glial, and epithelial cell types. In addition, DNA
      binding by EGR-1, a transcription factor structurally related to WT1, increased
      during differentiation of P19 EC and embryonic stem cells. To investigate the
      possible functional consequences of DNA binding by WT1, we examined the
      expression levels of two putative transcriptional targets of WT1, the insulin
      like growth factor 1 receptor and epidermal growth factor receptor. We found that
      after an initial induction, decreasing expression of the insulin-like growth
      factor I receptor is correlated with increasing WT1 expression. Our results
      demonstrate that expression of WT1 is induced in specific cell types during RA
      induced differentiation of P19 EC cells, reflecting the tissue-specific
      expression of WT1 in vivo. Therefore, we believe that P19 EC cells are a suitable
      system to study activation and function of WT1 during differentiation.

PMID- 9040936
TI  - Cyclin-dependent kinase inhibitor expression in pulmonary Clara cells transformed
      with SV40 large T antigen in transgenic mice.
AB  - Expression of cell cycle regulatory genes in mouse lung was investigated in
      transgenic models for Clara cell transformation. Clara cells were transformed by
      generating transgenic mice in which the SV40 large T antigen was expressed under
      the control of the mouse Clara cell M(r) 10,000 protein promoter. The resulting
      lung tumors express the large T antigen in normal Clara cells and in tumors, and
      these tumors express reduced levels of CC10 mRNA. The expression of cell cycle
      regulatory protein, p53, and the cyclin-dependent kinase inhibitors was analyzed
      by Northern blot analysis and in situ hybridization throughout the progression of
      Clara cell transformation in the lung. Increases in specific cyclin-dependent
      kinase inhibitor steady-state mRNA levels were detected in p15, p18, p27, and p57
      during tumor progression. The expression of p15, p57, and p21 mRNAs were verified
      by in situ hybridization. Using this approach, regulatory genes have been
      identified that may be involved in the regulation of Clara cell differentiation.

PMID- 9040937
TI  - A temperature-conditional mutant of simian virus 40 large T antigen requires
      serum to inhibit myogenesis and does not induce DNA synthesis in myotubes.
AB  - The temperature-conditional mutant tsA58 of SV40 large T antigen (Tag) increases
      the proliferation rate and the number of cell divisions in primary murine and
      human myogenic cells when expressed under permissive conditions (i.e., at 33
      degrees C in medium containing high levels of serum). Under these conditions, Tag
      also prevents terminal differentiation. Under nonpermissive conditions (i.e., at
      39 degrees C in medium containing low levels of serum) in which Tag is largely
      inactive, proliferation is arrested, and differentiation occurs. However, even at
      a permissive temperature, the removal of serum induced myosin expression and the
      fusion of myogenic cells, which continued to express functional Tag. Although Tag
      was complexed with pRb, as expected from a functional protein, proliferation was
      nevertheless arrested, and differentiation was induced. Consistent with these
      findings, the exposure of Tag-expressing differentiated myotubes to serum at 33
      degrees C did not reinduce DNA synthesis in these cells. Thus, in myogenic cells,
      temperature-conditional mutants of Tag stimulate proliferation in the presence of
      serum but neither prevent terminal differentiation in the absence of serum nor
      induce DNA synthesis once complete withdrawal from the cycle has occurred.

PMID- 9040938
TI  - Inactivation of retinoblastoma family proteins by SV40 T antigen results in
      creation of a hepatocyte growth factor/scatter factor autocrine loop associated
      with an epithelial-fibroblastoid conversion and invasiveness.
AB  - SV40 T antigen (LT) is an oncoprotein that inactivates nuclear regulators such as
      retinoblastoma (RB) family proteins and p53. We recently reported that in Madin
      Darby canine kidney (MDCK) epithelial cells the binding of LT to RB family
      proteins results in a massive apoptosis and a concomitant down-regulation of c
      myc. Here, we show that LT causes loss of epithelial differentiation and induces
      invasiveness. MDCK cells expressing wild-type LT, but not mutants unable to bind
      RB, exhibit a fibroblast-like morphology, show a strong down-regulation of the
      vHNF1 transcription factor and acquire invasive properties. The stable
      retransformation of MDCK(LT) with a RB and/or c-myc-expressing vector restores
      the expression of epithelial characteristics. Our data therefore suggest an
      important role for RB and c-myc in modulating the epithelial phenotype both
      during normal tissue development and in invasive processes. In addition, when
      grown in collagen gels, the MDCK(LT) cells form branching tubules, and their
      conditioned media produce the scattering of monolayer cultured MDCK cells. These
      last properties are reminiscent of those induced by hepatocyte growth
      factor/scatter factor (HGF/SF). Moreover, the HGF/SF protein was detected by
      Western blotting in the MDCK(LT)-conditioned medium. The production of HGF/SF is
      specifically induced by LT-RB inactivation, because Ras transformation of MDCK
      cells fails to induce the production of this factor. These results demonstrate
      that inactivation of RB family proteins in these cells is at the origin of a
      HGF/SF autocrine loop.

PMID- 9040939
TI  - Transactivation through Ets and Ap1 transcription sites determines the expression
      of the tumor-suppressing gene maspin.
AB  - Tumor invasion and metastasis are processes poorly understood at the molecular
      level. Maspin is a serine protease inhibitor (serpin) with tumor-suppressing
      function in the mammary gland. Maspin gene expression is decreased with
      malignancy and is lost in metastatic cells. We show in this report that
      differential expression of maspin in normal and carcinoma-derived mammary
      epithelial cells is regulated at the transcriptional level. We have identified
      the Ets and Ap1 sites in the maspin promoter that are active in regulating maspin
      expression in normal mammary epithelial cells but inactive in tumor cells. The
      Ets site alone is sufficient to activate transcription in a heterologous
      promoter, whereas the Ap1 site cooperates with Ets in activation. The enhancing
      function by Ets and Ap1 elements is decreased in primary tumor cells (21NT) and
      is abolished in invasive tumor cells (MDA-231). Thus, loss of maspin expression
      during tumor progression results at least in part from the absence of
      transactivation through the Ets and Ap1 sites.

PMID- 9040940
TI  - Large induction of c-Myc is not essential for the mitogenic response of Swiss 3T3
      fibroblasts.
AB  - Quiescent Swiss 3T3 fibroblasts can be stimulated to reenter the cell cycle
      following stimulation with growth factors. Among these, bombesin is a potent
      mitogen for Swiss 3T3 cells and can act synergistically with insulin to stimulate
      DNA synthesis through protein kinase C-independent pathways. One of the earliest
      nuclear responses of quiescent cells treated with a combination of bombesin and
      insulin is a dramatic increase in c-Myc expression, and it has been suggested
      that this proto-oncogene plays a central role in the mitogenic response. In the
      present study, we have taken two approaches to study the relationship between c
      Myc expression and the reinitiation of DNA synthesis. First, low concentrations
      of bombesin, in the presence of insulin, stimulated DNA synthesis in Swiss 3T3
      fibroblasts in the absence of a large increase in c-myc mRNA or protein levels.
      Second, selective down-regulation of phorbol ester-inducible protein kinase C in
      Swiss 3T3 cells resulted in a 90% decrease in the induction of c-myc mRNA and an
      80% reduction in Myc protein expression but did not affect the mitogenic response
      to bombesin and insulin. These observations were confirmed in detailed dose
      response and time-course experiments. We conclude that the large induction of c
      Myc is not an essential event for the entry of Swiss 3T3 fibroblasts into S
      phase. Quantitation of Myc protein levels using a sensitive ELISA indicated that
      quiescent cells could enter S phase with only 450 c-Myc molecules per cell. These
      results indicate that cells in the G0 phase of the cell cycle can be stimulated
      to reinitiate DNA synthesis with only marginal increases in Myc protein
      expression.

PMID- 9040942
TI  - The role of p27kip1 in the in vitro differentiation of murine keratinocytes.
AB  - We have studied the regulation of cyclins and cyclin-dependent kinase activities
      during differentiation of primary mouse keratinocytes. Differentiation was
      induced by placing primary murine keratinocytes into suspension culture, under
      conditions which prevent cells from attaching to any surface. This treatment
      induces synthesis of keratin 1, one of the earliest known markers of keratinocyte
      differentiation, and also results in a profound change in the regulation of G1
      and S-phase cyclins and their associated proteins as well as their activities.
      The placement of cells in suspension culture reduced cyclin A, D1, and E kinase
      activity within 6 h, accompanied by the cessation of DNA synthesis. K1 mRNA
      levels were observed to increase after this period, supporting the hypothesis
      that cell cycle withdrawal precedes the differentiation program. Our data further
      revealed that the p27kip1 protein level and associated cyclin-dependent kinase
      inhibitory activity increased when keratinocytes were induced to differentiate.
      Pretreatment of adherent keratinocytes with p27kip1 antisense oligonucleotides
      dramatically reduced the accumulation of p27kip1 protein upon subsequent
      suspension culturing and prevented the onset of differentiation independently of
      the loss of cyclin-dependent kinase activities. Although antisense
      oligonucleotide treatment inhibited differentiation, it did not prevent growth
      arrest. Therefore, the differentiation of primary mouse keratinocytes required a
      function of Kip other than the inhibition of cyclin-associated activities, and we
      suggest that this requirement may reflect a novel Rb kinase activity present in
      Kip immune complexes, which is dependent on the presence of cyclin D3. Thus, the
      placement of keratinocytes in suspension induces a program that includes loss of
      cyclin activity, which is linked to terminal growth arrest, and an induction of
      p27kip1, which is linked to the differentiation program.

PMID- 9040941
TI  - Tyrosine kinase signaling regulates Wiskott-Aldrich syndrome protein function,
      which is essential for megakaryocyte differentiation.
AB  - Platelets are produced from megakaryocytes differentiated from megakaryoblasts,
      but the differentiation mechanism still remains unknown. Here, we demonstrate
      that a tyrosine kinase signaling regulates Wiskott-Aldrich syndrome protein
      (WASP), which is essential for megakaryocyte differentiation. MEG-01
      megakaryoblastic cells differentiate into large multinucleated megakaryocyte-like
      cells characterized by microvesicle formation with a protein kinase C (PKC)
      activator, 12-O-tetradecanoylphorbol 13-acetate. With parallel to the
      differentiation, WASP begins to accumulate at microvesicles with actin filaments
      and associates with tyrosine-phosphorylated Shc, the phosphorylation of which is
      induced. Moreover, a tyrosine kinase inhibitor, herbimycin A, blocked not only
      phosphorylation of Shc but also microvesicle formation without affecting cell
      enlargement and multinucleation, whereas a PKC inhibitor, H-7, completely
      inhibited all these processes. Because WASP also binds to Ash/Grb2 SH3 domains
      and the association of Ash/Grb2 and Shc is induced by 12-O-tetradecanoylphorbol
      13-acetate treatment, a signaling pathway, PKC-tyrosine kinase-Shc-Ash/Grb2-WASP,
      is suggested for regulating megakaryocyte differentiation. In addition, WASP
      antisense oligonucleotide treatment abolishes both microvesicle formation and
      gathering of actin filaments. These data clearly show that WASP controls the
      assembly of actin filaments required for microvesicle formation downstream of PKC
      tyrosine kinase.

PMID- 9040943
TI  - Involvement of the transcription factor NF-IL6 in phorbol ester induction of P
      glycoprotein in U937 cells.
AB  - Previously, we showed that the nuclear factor NF-IL6 binds and trans-activates
      the promoter of the human multidrug resistance gene (MDR1) encoding P
      glycoprotein (N. J. Combates et al., J. Biol. Chem., 269: 29715-29719, 1994). In
      this study, we investigated the physiological relevance of MDR1 gene regulation
      by NF-IL6 in response to PMA (phorbol 12-myristate 13-acetate)-induced
      differentiation. Treatment of U937 cells, a human promonocytic cell line, with
      PMA induced their differentiation along the macrophage/monocytic cell lineage.
      The cellular changes were found to be accompanied by an increase in P
      glycoprotein expression at the cell surface. PMA treatment of U937 cells also
      resulted in the synthesis of the three forms of NF-IL6 and an enhanced DNA
      binding activity of nuclear extracts to a probe derived from the MDR1 promoter.
      The majority of the DNA-protein complex could be supershifted by an NF-IL6
      reactive antibody but not by antibodies for CAAT/enhancer binding protein alpha
      and delta, c-fos, or c-jun. Furthermore, transient transfection studies
      demonstrated that PMA enhanced the activity of a MDR1 promoter-driven luciferase
      gene construct to a greater extent as compared with the activity of a reporter
      construct containing mutations within the NF-IL6 responsive element. These
      results indicate a correlation between NF-IL6 gene expression and the regulation
      of the MDR1 gene. Furthermore, these observations also suggest that P
      glycoprotein expression is part of the macrophage differentiation process.

PMID- 9040944
TI  - Cloning and characterization of phorbol ester differentiation-resistant U937 cell
      variants.
AB  - Differentiation-resistant U937 cells were derived from parental U937 human
      promonocytic leukemia cells by selecting for a nonadherent phenotype in cell
      cultures continuously exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA).
      Subsequent analysis indicated no differences between wildtype (wt) and resistant
      U937 cells with respect to protein kinase C (PKC) isozyme expression, activation,
      or down-modulation. The subcellular localization of PKCs is identical in wt and
      resistant cells with the exception of PKC beta 2, which no longer colocalizes
      with microtubules in the TPA-resistant cell lines. In contrast to wt-U937 cells,
      the resistant cells do not express beta 2-integrin adhesion molecules, cd11b and
      cd11c, on the cell surface following TPA treatment but do express cd11b and cd11c
      in intracellular vesicles. TPA stimulates the translocation of these vesicles to
      the cell surface in wt U937 cells but not in the resistant cells. These results
      suggest that events downstream of PKC activation may mediate cytoskeletal
      reorganization and beta 2-integrin transport to the cell surface in wt-U937 cells
      but not in the differentiation-resistant cells.

PMID- 9040945
TI  - Defective microtubule reorganization in phorbol ester-resistant U937 variants:
      reconstitution of the normal cell phenotype with nocodazole treatment.
AB  - Phorbol ester-induced beta 2-integrin transport to the cell surface is defective
      in cloned 12-O-tetradecanoylphorbol-13-acetate (TPA)-resistant U937 cell
      variants. Failure of the integrin-containing vesicles to reach the plasma
      membrane effectively blocks development of all integrin-mediated responses and
      the formation of a functional oxidase complex. Several lines of evidence
      suggested that the underlying cause of this defect may be the loss of regulatory
      elements in the cytoskeleton, which mediate microtubule stability and
      organization. Diminished protein kinase C (PKC) beta 2 association with
      microtubules correlated with the loss of heat-soluble microtubule-associated PKC
      binding proteins and the loss of TPA-inducible reorganization of the microtubule
      cytoskeleton in the resistant U937 variants. Treatment with the microtubule
      disrupting drug, nocodazole, was sufficient to induce the modest increase in
      cd11b surface expression associated with the release of this preformed integrin.
      Furthermore, brief nocodazole treatment followed by TPA treatment completely
      restored susceptibility to phorbol ester-induced differentiation in the resistant
      cell lines. The combination of nocodazole and TPA treatment also restored NADPH
      oxidase activity in the TPA-resistant clones. Results from these studies suggest
      that TPA-induced microtubule reorganization is a prerequisite for integrin
      vesicle translocation in U937 cells and that vesicle translocation to the plasma
      membrane may be a prerequisite for the transcriptional activation of cd11b and
      cd11c integrin genes in the early stages of monocyte differentiation.

PMID- 9040946
TI  - Collagenase 3 (matrix metalloproteinase 13) gene expression by HaCaT
      keratinocytes is enhanced by tumor necrosis factor alpha and transforming growth
      factor beta.
AB  - Collagenase-3 (matrix metalloproteinase 13; MMP-13) is a novel matrix
      metalloproteinase, the expression of which to date has only been detected in
      human breast carcinoma tissue and osteoarthritic cartilage. Here, we show that
      MMP-13 transcripts are expressed by human HaCaT keratinocytes but not by primary
      human epidermal keratinocytes. The levels of MMP-13 mRNAs in HaCaT cells were
      enhanced up to 130- and 45-fold by tumor necrosis factor alpha (TNF-alpha) and
      transforming growth factor beta (TGF-beta), respectively. The maximal induction
      of MMP-13 mRNAs by TNF-alpha was noted after a 6-h incubation, whereas with TGF
      beta, the maximal stimulation was observed after 24 h. The up-regulation of MMP
      13 mRNA abundance by TNF-alpha and TGF-beta was dependent on protein synthesis
      and was prevented partially by dexamethasone and retinoic acid. Nuclear run-on
      assays demonstrated activation of MMP-13 gene transcription by TNF-alpha
      maximally at the 2-h time point and by TGF-beta after 12 h of treatment.
      Incubation of HaCaT keratinocytes with TNF-alpha and TGF-beta also increased
      production of proMMP-13 into the culture media, as detected by Western blotting.
      Our data indicate that the MMP-13 gene is expressed by transformed epidermal
      keratinocytes, suggesting a role for MMP-13 in the invasive capacity of human
      epidermal malignancies.

PMID- 9040947
TI  - Apoptosis is accompanied by changes in Bcl-2 and Bax expression, induced by loss
      of attachment, and inhibited by specific extracellular matrix proteins in mammary
      epithelial cells.
AB  - Mammary epithelial cells (MEC) undergo programmed cell death (PCD) when deprived
      of serum and growth factors at high cell density but not at low density. The
      addition of epidermal growth factor and insulin to serum-free medium (SFM)
      completely restores cell survival. In this report, we examine the role of cell
      cell and cell-matrix interaction. When cell attachment is prevented, PCD is
      markedly accelerated. This effect is observed in cells collected at low or high
      density and is unaffected by calcium depletion. Cells plated in SFM on purified
      laminin, tenascin C, or collagen IV-coated dishes, as well as on dishes coated
      with endogenous extracellular matrix deposited by HC11 mammary cells, show
      reduced PCD. The addition of soluble laminin or tenascin C to suspension cultures
      of MECs also partially inhibits PCD. In contrast, no effect is seen with
      fibronectin or collagen I. These results indicate that reduced contact with a
      solid substrate contributes to the induction of PCD, which might partially
      explain the fact that it is only observed in confluent cultures. Ectopic Bcl-2
      expression in MCF-10-A and HC11 mammary cells results in a complete suppression
      of PCD. In MCF-10-A cells, the level of endogenous Bcl-2 increases when the
      survival factors epidermal growth factor and insulin are added to the SFM but is
      unaffected by cell density. On the contrary, Bax protein expression increases
      sharply with cell density but does not change upon addition of epidermal growth
      factor and insulin. When compared to lactating tissue, Bcl-2 protein levels
      decrease during mammary gland involution. Bax protein levels increase during
      lactation and remain high during involution. These data suggest that Bcl-2 and
      Bax might be intracellular mediators of signals that influence MEC apoptosis.

PMID- 9040948
TI  - Decreased activity of inducible nitric oxide synthase type 2 and modulation of
      the expression of glutathione S-transferase alpha, bcl-2, and metallothioneins
      during the differentiation of CaCo-2 cells.
AB  - Reactive oxygen species modulate the cell growth of a wide variety of mammalian
      cells. To determine whether oxidative metabolism is altered during the
      differentiation process, we studied the expression of pro- and antioxidant
      proteins in proliferating and differentiated CaCo-2 cells, a human colon
      adenocarcinoma cell line. Nitric oxide synthase type 2 (iNOS) produces nitric
      oxide (NO). Depending on its rate of synthesis, NO may either promote cellular
      and DNA damage or reduce the ability of other free radicals to induce cell
      injury. Using Western and Northern blot analysis and arginine conversion assay,
      we demonstrate that the expression of iNOS decreases when cells undergo
      differentiation. This biological event entails a diminished production of NO
      metabolites and correlates with the loss of activation of soluble guanylate
      cyclase activity. In differentiated cells, a 2-fold down-regulation of the
      nuclear factor kappa B activity was observed, suggesting that nuclear factor
      kappa B could be one of the iNOS gene regulatory factors in the CaCo-2 model. In
      parallel, we studied the expression of other antioxidant proteins including
      glutathione S-transferase alpha (GST alpha), bcl-2, and the metallothioneins
      (MTs). We show that the protein levels of GST alpha and MT increase during the
      differentiation of CaCo-2 cells, whereas bcl-2 levels decrease. Our investigation
      indicates that the expression of iNOS, GST alpha, bcl-2, and MT is associated
      with the enterocytic differentiation. The shift in the expression of specific
      antioxidant genes during CaCo-2 cell differentiation may occur to avoid
      alterations in the cell redox potential.

PMID- 9040950
TI  - Incorporation of beta-galactosidase-expressing endothelial cells into the
      skeletal muscle microvascular bed of mice.
AB  - Cloned murine endothelial cells (cEC) were used as a carrier system for
      introducing a foreign gene into the microvascular bed of the hind limb of inbred
      mice. cEC were transfected with a beta-galactosidase-neo fusion construct, which
      enables both selection for DNA uptake in the presence of G 418 and the staining
      of cells for beta-galactosidase activity. Transfected cEC adhered and integrated
      readily into confluent monolayers of nontransfected cEC (up to 26% of total cell
      number). Seeding lacZ-transfected cEC on explanted arteries revealed rapid
      adhesion of the cells (within minutes) to the intact endothelium. After injection
      of 10(6) transfected EC via the femoral artery into the microvascular bed of the
      hind limb their presence was documented by beta-galactosidase staining after
      various time periods (1 h to 4 wk). Implanted cEC were detected in numerous
      elements of the microcirculation both in frozen sections and in squash
      preparations of the hind limb muscle and in the femoral bone up to 4 wk after the
      injection. The microvascular bed of skeletal muscle of the mouse as a recipient
      site for transduced syngeneic endothelial cells is, thus, a suitable experimental
      model to study various strategies for somatic gene therapy.

PMID- 9040949
TI  - Transfer and expression of the interferon gamma gene in human endothelial cells
      inhibits vascular smooth muscle cell growth in vitro.
AB  - Intimal hyperplasia in blood vessels is primarily caused by the migration and
      proliferation of vascular smooth muscle cells. Excessive intimal thickening
      characterizes atherosclerosis as well as bypass graft and angioplasty failures.
      Endothelial cell-smooth muscle cell interactions and local cytokine production
      are important regulators of smooth muscle cell growth. Interferon gamma (gamma
      IFN), a product of T lymphocytes found in atherosclerotic lesions, inhibits
      smooth muscle cell proliferation in vitro. To determine if local delivery of
      gamma-IFN may be useful in the treatment or prevention of vascular proliferative
      diseases, we transferred the human gamma-IFN gene into endothelial cells isolated
      from human arteries and microvessels using a retroviral vector. Biologically
      active gamma-IFN was produced and secreted by gamma-IFN transduced endothelial
      cells, but not by control, nontransduced cells, or cells identically transduced
      with E. coli beta galactosidase (beta-gal). To more closely approximate the
      microenvironment of blood vessels, subconfluent smooth muscle cells were plated
      in coculture with control, nontransduced endothelial cells, gamma-IFN transduced
      endothelial cells, or beta-gal transduced endothelial cells. Smooth muscle cell
      growth was inhibited 30-70% by coculture with gamma-IFN transduced endothelial
      cells compared to coculture with beta-gal transduced or control endothelial cells
      (p < 0.05). Our results suggest endothelial cells modified to produce gamma-IFN
      may be a useful therapy in proliferative vascular diseases.

PMID- 9040951
TI  - Repeated intraportal injections of subtherapeutic islet cell isografts restore
      normoglycemia in streptozotocin-diabetic rats.
AB  - Poor engraftment and consequent loss of beta-cell mass could be one of the
      factors that are responsible for function loss after intraportal islet
      transplantation (Tx). Streptozotocin-diabetic rats were transplanted with
      syngeneic islets, which were injected into the portal vein via an indwelling
      catheter connected to a subcutaneous port. In Group I (n = 6), 1,000 islets were
      injected in a single dose into the liver. In Group II (n = 6), five doses of 200
      islets were repeatedly injected over a period of 14 days, for a total of 1,000
      islets. In Group III (n = 4), five decreasing doses of islets were injected over
      a period of 14 days, for a total of 750 islets. Nonfasting blood glucose (n-FBG)
      and body weight (b.wt.) were determined twice a week and an intravenous glucose
      tolerance test (IVGTT) was performed at 30 and 90 days. In Group I, n-FBG
      decreased in 2 wk from the time of first islet injection, averaging 110 +/- 21.9
      mg/dl at 1 mo (p < 0.05 vs. normal controls); this value was maintained
      throughout the 3-mo duration of the study. In Group II, n-FBG was normalized in 2
      wk averaging 90.2 +/- 25 mg/dL on day 12 (p = NS vs. normal controls) and 75.8 +/
      14.6 mg/dL at 1 month (p = NS vs. normal controls); this value was maintained
      throughout the 3-mo duration of the study. In Group III, n-FBG decreased to
      normal values in 2 wk, averaging 77 +/- 15.7 mg/dL at 1 mo (p = NS vs. normal
      controls), but normoglycemia was maintained for 40 days and then followed by a
      progressive increase. Only in Group II, KG (percent/min decline in glucose level)
      was not significantly different from that of normal controls (1.702 +/- 0.531 at
      1 mo and 1.676 +/- 0.891 at 3 mo), while it was significantly lower than normal
      controls in both Group I and III animals. Body weight increase after Tx
      correlated with the number of transplanted islets and at 90 days, Group III rats
      showed less increase than Groups I and II (p < 0.05), while no significant
      differences in b.wt. were recorded between Group I and II. The findings indicate
      that intraportal islet Tx, injected repeatedly and in small doses, produced
      better metabolic effects than injection of the same total number of islets in a
      single dose.

PMID- 9040952
TI  - Insulin secretion and glucose tolerance after islet transplantation in rats with
      noninsulin-dependent diabetes induced by neonatal streptozotocin.
AB  - The present study was designed to identify in a model of noninsulin-dependent
      diabetes induced by neonatal streptozotocin (n0-STZ), the long-term consequences
      of an islet graft upon 1) glucose handling of the recipient and, 2) glucose
      response of the residual beta cells in the recipient pancreas. We have examined,
      4 and 8 wk after islet implantation under the kidney capsule of syngeneic
      diabetic n0-STZ rats, their tolerance to glucose administered in vivo, together
      with their insulin release in response to glucose in vivo (oral glucose tolerance
      test) as well as in vitro (perfused pancreas). The results in the islet-grafted
      n0-STZ rats, were compared to those obtained in nongrafted nondiabetic rats and
      nongrafted n0-STZ rats. Our study shows that transplanting a limited number (900)
      of adult islets under the kidney capsule reverses to normal, many parameters of
      the noninsulin-dependent diabetic state in the n0-STZ rat model: these include
      body weight, basal plasma glucose in both the nonfasted and postabsorptive
      states, and basal plasma insulin in the postabsorptive state. Furthermore,
      tolerance to oral glucose administration was greatly improved in the transplanted
      rats and it was correlated with restoration of a manifest glucose-induced insulin
      secretion in vivo as evaluated (delta 1) during an oral glucose tolerance test.
      Our data clearly show that the insulin response to glucose from the endogenous
      pancreas of n0-STZ diabetic rat was not really improved by long-term (8 wk) basal
      normoglycemia. More precisely, we were able to detect a slight but significant
      improvement of the early phase of insulin release in vitro in response to
      glucose; however, the overall insulin response remained 15 times lower than the
      normal one with no reappearance of the late phase of insulin release. After
      cessation of glucose stimulation in vivo, off-response of insulin, which is also
      a landmark of the impaired insulin release by the beta cells of n0-STZ rats, was
      still detectable in the perfused pancreas of the transplanted n0-STZ rats.
      Finally, because the reactivity to glucose of the endogenous residual beta cells
      was not regained, the insulin released in vivo during the oral glucose test in
      the graft-bearing n0-STZ rats can be attributed mainly to functioning of the
      grafted islets population.

PMID- 9040953
TI  - Effects of caffeine and acetylcholine on glucose-stimulated insulin release from
      islet transplants in mice.
AB  - In mouse islet grafts under the kidney capsule, the potentiating responsiveness
      to acetylcholine was markedly attenuated after a few weeks. The question arose as
      to whether transplanted islets show an decreased responsiveness to potentiators
      in general. The effect of caffeine on glucose-induced insulin secretion was,
      therefore, examined. Intrastrain transplantation was performed in NMRI and BALB/c
      mice, and islet grafts were removed and perifused in vitro after 3 and 12 wk. In
      grafts from both NMRI and BALB/c mice, 16.7 nmol/L glucose induced a biphasic
      insulin release. When 1 or 5 mmol/L caffeine was included in the perifusion
      medium, there was a marked potentiation of the glucose-induced insulin release
      that was at least as responsiveness as fresh untransplanted islets. In the
      absence of caffeine, 3-wk-old BALB/c grafts reacted less strongly to
      acetylcholine than did untransplanted islets. The addition of 1 mmol/L caffeine
      did not enhance the potentiating effect of acetylcholine, whether in
      untransplanted or transplanted islets. Rather, the interaction between caffeine
      and acetylcholine appeared negative. We concluded that the glucose-induced
      insulin secretion exhibits a diminished potentiatory responsiveness to
      acetylcholine but not to caffeine. The displacement and denervation of
      transplanted islets is likely to affect either the cholinergic receptors or their
      mediated influence on intracellular calcium.

PMID- 9040955
TI  - Development of an automated computer-controlled islet isolation system.
AB  - Before clinical islet transplantation can become an effective and reliable
      treatment for type 1 diabetic patients, there must be significant improvements in
      the methods employed for the isolation of islets of Langerhans. We have developed
      an automated cell extraction system (ACES), which allows computer control of the
      isolation process. As well, it incorporates a novel method of recombining
      dissociated pancreatic tissue. Following initial system design and testing to
      determine the optimal system configuration, a series of 12 consecutive canine
      islet isolations were performed. Pancreases were perfused with collagenase via
      the duct and dissociated and recombined using either the standard Ricordi-based
      protocol (group 1, n = 6) or dissociated and recombined using the ACES system
      (group 2, n = 6). A total of 90.8 +/- 21 x 10(3) islet equivalents (IE) (mean +/-
      SEM) were recovered in group 1 vs. 99 +/- 14 x 10(3) IE in group 2 (p = NS,
      student unpaired t-test). Following Ficoll purification the recovery was 56.2 +/-
      14 x 10(3) IE for group 1 vs. 54.7 +/- 11 x 10(3) IE for group 2 (p = NS).
      Viability was equivalent with an 8.6-fold increase in insulin secretion for group
      1 and an 8.8-fold increase for group 2 when the islets were exposed to high
      glucose solution supplemented with IBMX (3-isobutyl-1-methylxanthine) during
      static incubation. In vivo function was equivalent following transplantation of
      2000 IE under the kidney capsule of alloxan-induced diabetic nude mice with five
      of six and five of seven mice surviving long-term (> 50 days posttransplant)
      (groups 1 and 2, respectively). This data shows that an entirely automated
      pancreatic islet extraction system can result in effective canine islet recovery
      without compromising islet yields and viability. The ACES system has several
      advantages over the standard isolation protocol. These include: 1) computer
      control and monitoring over all phases of the isolation, 2) a single-use sterile
      disposable tubing set, and 3) a novel method of tissue recombination.

PMID- 9040954
TI  - Effect of fusidic acid on pancreatic islet allograft rejection.
AB  - We examined in fully mismatched rats, the survival of pancreatic islet allografts
      in recipients treated with either fusidic acid (FA), an antistaphyllococcal
      antibiotic that has been shown to possess an immunosuppressive effect in vitro
      and in vivo, or cyclosporin-A (CsA). Islets were isolated by collagenase
      digestion, separated from acinar tissue by handpicking under a dissecting
      microscope and transplanted into the liver by portal vein injection of
      streptozotocin(STZ)-induced diabetic rats. The results indicated that while a
      temporary immunosuppression with CsA achieved an indefinite islet allograft
      survival, FA administered to recipients daily was not able to prevent islet
      allograft rejection across a major histocompatibility barrier. We conclude that
      despite the fact that fusidic acid has been claimed to act as an
      immunosuppressant drug in vitro with effects similar to those of CsA, unlike CsA,
      FA given either orally or by s.c. injection was not effective to prolong islet
      allograft survival in vivo.

PMID- 9040957
TI  - Cyclosporine does not inhibit the process of revascularization of pancreatic
      islet transplantation.
AB  - The immunosuppressive drug cyclosporin-A (CsA) has been widely used to prevent
      pancreatic islet allograft rejection. Because it has been suggested that CsA may
      inhibit the process of revascularization of transplanted islets, the purpose of
      the study was to analyze by a double indirect immunofluorescence technique the
      revascularization process of isolated islets grafted in the liver and in the
      renal subcapsular space of rats treated with immunosuppressive doses of CsA.
      Lewis rats were grafted with either Lewis (isografts) or Wistar (allografts)
      pancreatic islets obtained by collagenase digestion. Rats were killed at
      different days after implantation and the liver and kidney bearing the grafted
      islets were snap frozen and immunohistochemically stained with a double
      immunofluorescence technique using a rabbit antifactor-VIII antiserum (which
      labels endothelial cells) and a guinea pig antiinsulin antibody. Islets implanted
      into nonimmunosuppressed hosts completed revascularization by days 3-7 after
      transplantation, as shown by the detection of endothelial cells within and
      surrounding the islets. The identical staining pattern of revascularization was
      observed in nonrejecting allografts as well as in isografts treated with CsA. We
      conclude that CsA did not inhibit the process of revascularization of rat islets
      after free transplantation. This finding is relevant for human islet
      transplantation, where CsA is currently employed to prevent kidney and islet
      allograft rejection.

PMID- 9040956
TI  - Isolation and characterization of a cell line from the epithelial cells of the
      human fetal pancreas.
AB  - Pancreatic cell lines are useful for basic studies of pancreatic biology and for
      possible application to cell transplantation therapies for diabetes. A retroviral
      vector expressing simian virus 40 (SV40) T antigen and H-rasval12 was used to
      infect a monolayer culture of epithelial cells from an 18-wk human fetal
      pancreas. Infected cells gave rise to a clonal epithelial cell line, designated
      TRM-1. This cell line expresses epithelial markers as well as gult2 and small
      amounts of insulin and glucagon. TRM-1 is the first cell line to be generated
      from the human fetal pancreas and also the first cell line derived directly from
      the fetal pancreas of any species. The approach that we have used to develop TRM
      1 should be applicable to isolating cell lines from other stages of human
      pancreatic development.

PMID- 9040958
TI  - Allogeneic hepatocyte transplantation using FK 506.
AB  - Hepatocyte transplantation is an intriguing alternative to orthotopic liver
      transplantation. While engraftment of syngeneic hepatocytes can be achieved with
      relative ease, engraftment of allogeneic hepatocytes has been far more
      complicated. We used FK 506 (Tacrolimus), a novel and highly efficient
      immunosuppressant, which has been reported to augment liver regeneration in rats.
      Recipients of isolated syngeneic (LEW) and allogeneic (Wistar F.) rat hepatocytes
      (major histocompatibility barrier) recieved different immunosuppressive regiments
      with FK 506 or Cyclosporine A (CsA). Mature syngeneic hepatocytes could be
      retrieved up to post op day 300 with the lowest number of hepatocytes on post op
      day 20. Following allogeneic transplantation, no mature hepatocytes could be
      identified after post op day 10, though ductular like structures within the
      spleen were found in FK 506 but not CsA-treated animals. The epithelial cells of
      ductular like structures exhibit cytological features of CK-19 positive cells.
      Our results suggest that under CsA or FK 506 immunosuppression long-term survival
      of mature allogeneic hepatocytes within the spleen cannot be achieved across a
      major histocompatibility barrier though FK 506 allows engraftment of allogeneic
      donor type ductular cells.

PMID- 9040959
TI  - Intraretrosplenial cortical grafts of fetal cholinergic neurons and the
      restoration of spatial memory function.
AB  - The retrosplenial cortex (RSC) receives cholinergic afferent fibers from the
      medial septal nucleus and diagonal band of Broca (DBB) by way of the cingulate
      bundle and the fornix. Bilateral lesions of both the cingulate and fornix
      pathways result in a complete depletion of cholinergic input to the RSC. In the
      present study we have examined the effects of transplanting cholinergic neurons
      from fetal rat pups to the RSC of adult rats following lesions of the cingulate
      bundle and fornix. The animals with lesions exhibited severe spatial memory
      impairments with a complete loss of extrinsic cholinergic afferents to the RSC.
      Animals with intraretrosplenial cortical transplants exhibited significant
      improvements in learning and memory performance as revealed by decreased escape
      latencies in spatial reference memory tests, increased numbers of platform
      crossings in spatial navigation tests, and a higher percentage of correct choices
      in a spatial working memory task. These improvements appeared to be
      cholinergically mediated because atropine administration significantly disrupted
      spatial navigation performance. The survival of the transplanted cholinergic
      neurons and their innervation of the RSC were characterized using a monoclonal
      antibody to choline acetyltransferase (ChAT). The staining of graft-derived ChAT
      positive fibers also revealed a pattern of innervation that mimicked that of the
      cholinergic input in normal animals. These results indicate that
      intraretrosplenial cortical transplants of cholinergic neurons can rectify
      spatial memory deficits produced by the loss of intrinsic cholinergic afferents
      from the medial septal nucleus.

PMID- 9040960
TI  - First human myoblast transfer therapy continues to show dystrophin after 6 years.

PMID- 9040966
TI  - T-cells and macrophages in HIV disease.

PMID- 9040967
TI  - B-lymphocytes and autoantibody profiles in HIV disease.

PMID- 9040972
TI  - Standard and special tests for the barrier integrity of medical gloves. Part I:
      The use and abuse of vinyl gloves by health care workers allergic to latex.

PMID- 9040969
TI  - HIV and psoriasis.

PMID- 9040971
TI  - Adverse reactions to trimethoprim-sulfamethoxazole.

PMID- 9040973
TI  - Mast cell disease.

PMID- 9040974
TI  - Human phenotypes. The atopic and seborrheic: Part III.

PMID- 9040970
TI  - Allergic manifestations in AIDS.

PMID- 9040975
TI  - A Behcet-like disease presenting as ulcerative stomatitis and scarring pustular
      lesions of the face.
AB  - Behcet's disease is a complex multisystem disease of unknown origin. It presents
      clinically as oral, pharyngeal, and genital ulcerations, uveitis, and
      inflammatory papulopustules. Diagnosis is made clinically since laboratory and
      histologic observations are not specific. We present a patient who, despite the
      absence of eye and genital lesions, seems best viewed as having Behcet's disease.

PMID- 9040968
TI  - Rheumatologic manifestations of HIV infections.

PMID- 9040976
TI  - Cutaneous hyperpigmentation and polyglandular autoimmune syndrome type II.
AB  - Primary adrenal insufficiency (Addison's disease) may initially present with
      cutaneous hyperpigmentation. Addison's disease, when associated with autoimmune
      thyroid disease and/or insulin-dependent diabetes mellitus, is referred to as
      polyglandular autoimmune syndrome type II. We present the case of a patient who
      initially was diagnosed as having Grave's disease and eventually Addison's
      disease due to persistent cutaneous hyperpigmentation, fatigue, weight loss,
      hypotension, hyponatremia, peripheral eosinophilia, and positive results of a
      synthetic corticotropin stimulation test. Addison's disease, polyglandular
      autoimmune syndrome type II, and cutaneous hyperpigmentation are reviewed.

PMID- 9040977
TI  - Erythema ab igne caused by a car heater.
AB  - Erythema ab igne is a reticulated erythematous hyperpigmented eruption that
      occurs after chronic exposure to heat. In the past, the shins were the most
      common area of involvement, but with the widespread availability of central
      climate control in most buildings the incidence has decreased dramatically. New
      causes of erythema ab igne have been noted that have been caused by such heat
      sources as therapeutic chairs with built-in heaters. We present a case in which
      prolonged and close contact of the legs to a car heater led to erythema ab igne.
      Practitioners must be aware of the changing causes of erythema ab igne so that an
      appropriate history can be obtained.

PMID- 9040978
TI  - Granular cell basal cell carcinoma.
AB  - Granular cell basal cell carcinoma is an unusual histopathologic subtype of basal
      cell carcinoma in which some or all of the neoplastic cells show cytologic
      features of granular cells. These distinctive cells contain abundant eosinophilic
      cytoplasm housing numerous fine and coarse refractile granules. This report
      documents the first case of granular cell basal cell carcinoma in which the
      collections of neoplastic granular cells arise in direct contiguity with an
      otherwise ordinary nodular basal cell carcinoma. Granular cell basal cell
      carcinoma is a unique histopathologic variant of basal cell carcinoma that is
      rare, this report representing the sixth case in the world literature.

PMID- 9040979
TI  - Erosive adenomatosis of the nipple: a benign imitator of malignant breast
      disease.
AB  - We present the case of a 66-year-old white woman with erosive adenomatosis of the
      nipple, in which an initial diagnosis of Paget's disease was considered.
      Diagnosis of erosive adenomatosis of the nipple was made by the characteristic
      histologic findings on a biopsy specimen. This essentially benign condition is
      generally unilateral, with erythema, crusting, and hardening of the nipple.
      Histologic findings of erosive adenomatosis of the nipple eliminate the diagnosis
      of invasive carcinoma or Paget's disease, which can have clinical features
      similar to those of erosive adenomatosis of the nipple.

PMID- 9040980
TI  - Immunogenetics of disease resistance in fish: a comparative approach.
AB  - The study of the genetic regulation of infectious disease resistance depends on
      the availability of inbred lines or selection lines of the species under
      investigation. The small numbers of such lines of fish has limited the strategy
      in teleosts to studies of associations between disease and immune/health traits.
      Attempts to correlate genetic differences in immune responsiveness with survival
      after experimental challenge with pathogenic bacteria have failed to define
      immune parameters that can substantially aid selection for genetic resistance to
      infectious diseases. Advantages and disadvantages of selection strategies as
      illustrated by mouse and chicken models are discussed. In this study we summarize
      the present situation in fish as well as our attempts to develop gynogenetic
      lines of carp for immunogenetic research.

PMID- 9040982
TI  - Phagocytes from both vertebrate and invertebrate species use "coiling"
      phagocytosis.
AB  - Coiling phagocytosis has been observed previously only by chance, and there has
      been no systematic investigation of this uptake mechanism. Therefore, a
      comparative electron microscopical study was performed. Different human and
      murine cell populations, phagocytes from various vertebrate and invertebrate
      species, and predatory amoebae were incubated with Borrelia burgdorferi, one of
      the microbes known to induce coiling phagocytosis, to study the uptake mechanisms
      used. In this model, coiling phagocytosis was observed with both vertebrate and
      invertebrate species but not with amoebae. With cells from humans and mice, this
      uptake mechanism was restricted to phagocytic cells of myeloid origin. The coiled
      membrane gaps did not give rise to phagosomes; instead, membrane fusion was
      followed by membrane dissipation. Thus, coiling of B. burgdorferi apparently is
      an alternative uptake mechanism used by metazoan phagocytes, involving special
      membrane processing. However, coiling phagocytosis may show different features
      with different microbes.

PMID- 9040981
TI  - The effects of copper on actin and fibronectin organization in Mytilus
      galloprovincialis haemocytes.
AB  - The effects of copper on actin and fibronectin organization in Mytilus
      galloprovincialis haemocytes were studied. The Cu2+ exposure of mussels caused
      severe perturbations in haemocyte actin and fibronectin organization with respect
      to non-exposed organisms. Cytoskeletal actin was analysed by indirect
      immunofluorescence, using an antitotal actin monoclonal antibody, and by
      rhodamine-conjugated phalloidin. The majority of haemocytes from Cu(2+)-exposed
      mussels displayed a round morphology, with short and blunt filopodia; they lacked
      the polarized phenotype which was typical in control samples. The cytoskeleton
      alteration, more evident after phalloidin staining, resulted in the disappearance
      of filamentous actin. The actin cortical meshwork also appeared disorganized. The
      cytoskeletal morphology studied by transmission electron microscopy after
      negative staining of Triton X-100-treated haemocytes confirmed these
      observations. The structural organization of actin when analysed by Western
      blotting showed a larger number of Triton-soluble actin pools in treated mussel
      haemocytes. Fibronectin was studied by indirect immunofluorescence using a
      polyclonal antiserum directed against mussel fibronectin. In treated mussels,
      fibronectin appeared to be strongly disorganized and its levels decreased in both
      haemocytes and haemolymph. The mechanism(s) of the copper-induced alterations on
      actin and fibronectin organization in mussel immunocytes is discussed.

PMID- 9040988
TI  - Synthesis and biological evaluation of novel pyrrolidine-2,5-dione inhibitors as
      potential anti-tumour agents.
AB  - Several novel pyrrolidine-2,5-dione based compounds have been synthesised and
      evaluated for their biological activity against human placental aromatase (AR),
      rat testicular 17 alpha-hydroxylase/17,20-lyase (P450(17) alpha) and bovine
      cholesterol side chain cleavage (CSCC). The compounds showed good inhibition
      towards AR with 1-cyclohexyl-3-[2'(4"-aminophenyl) ethyl] pyrrolidine-2,5-dione
      (3) (IC50 = 23.8 +/- 4.6 microM) and 1-octyl-3-[2'(4"-aminophenyl) ethyl]
      pyrrolidine-2,5-dione (4) (IC50 = 24.6 +/- 1.8 microM) showing equipotent
      activity with Aminoglutethimide (AG) (IC50 = 20.0 +/- 2.6 microM, Ki = 11.0 +/-
      2.0 microM). Of the compounds tested for P450(17) alpha activity, 3 (IC50 = 18.5
      +/- 1.9 microM) again showed the highest activity, being equipotent to
      Ketoconazole (IC50 = 12.1 +/- 2.9 microM). 3 was a poor inhibitor of CSCC with
      some 22% inhibitory activity at an inhibitor concentration of 200 microM, as
      compared to AG with 72% inhibitory activity under the same conditions. The
      compounds proved themselves to be excellent lead compounds and supported the
      novel models developed by Ahmed for AR and P450(17) alpha.

PMID- 9040984
TI  - Conservation of an alpha 2 domain within the teleostean world, MHC class I from
      the rainbow trout Oncorhynchus mykiss.
AB  - A full-length cDNA clone (Onmy-UA-C32) encoding a major histocompatibility
      complex (MHC) class I heavy chain was isolated from a rainbow trout thymus cDNA
      library. Onmy-UA-C32 alpha I and III extracellular domains were most similar to
      other salmonids (92 and 86% at the nucleotide and amino acid level) but
      interestingly the alpha II domain is closer to that of the carp (74 and 73%) and
      zebrafish (75 and 70%). In addition, Onmy-UA-C32 displays conservation of
      residues known to be essential for the function and structure of MHC class Ia
      molecules. Northern blot hybridization with alpha 2 or 2-3 domain probes of Onmy
      UA-C32 detected high expression (2.6 kb) of this gene in the spleen, thymus,
      kidney, heart and intestine with lower levels being observed in the brain and
      liver. No tissues were found to be negative indicating a ubiquitous pattern of
      expression for Onmy-UA-C32. Onmy-UA-C32 may therefore represent a MHC class Ia
      gene in trout as well as providing new insights regarding the evolution of the
      MHC within teleost species.

PMID- 9040987
TI  - Effect of prolactin, in vivo and in vitro, upon heterophil phagocytic function in
      the ring dove (Streptopelia risoria).
AB  - The purpose of this study was to investigate the effects of prolactin, both in
      vitro and in vivo, upon heterophil phagocytic activity of the ring dove,
      Streptopelia risoria. In vitro incubation of heterophils with either 0.1 or 100
      micrograms/mL of ovine prolactin for 2 h-significantly increased both latex bead
      phagocytosis and Nitroblue tetrazolium (NBT) reduction, an index of phagocytic
      metabolic activity. Ring doves given antigen demonstrated an increase in latex
      bead phagocytosis and NBT reduction. The greatest increase in both of these
      parameters was observed in those birds which possessed elevated plasma prolactin
      concentrations, either through exogenous administration or naturally through
      being in the later stages of incubation. These results suggest that during the
      incubation period of the avian breeding cycle there is an increase in phagocytic
      activity which is a direct consequence of the elevation shown by these birds in
      the concentration of plasma prolactin.

PMID- 9040985
TI  - Deactivation of primed respiratory burst response of goldfish macrophages by
      leukocyte-derived macrophage activating factor(s).
AB  - Macrophage activation factors (MAF), induced maximal priming of the respiratory
      burst response in GMCL after 6 h of stimulus, but by 24 or 48 h no priming effect
      was observed. Bacterial lipopolysaccharide (LPS) also primed the respiratory
      burst of goldfish macrophages, but the kinetics of priming were different from
      that induced by MAF. LPS induced a gradual increase in priming potential over 48
      h of cultivation. Co-stimulation of macrophages with MAF and LPS resulted in
      enhanced priming of respiratory burst activity compared to either factor alone;
      however, the kinetics of priming were similar to those induced by MAF only. The
      MAF antagonized the ability of LPS to prime the respiratory burst over extended
      cultivation. The priming kinetics of the respiratory burst induced by MAF and/or
      LPS were not unique to GMCL, but were also similar for primary cultures of IVDKM.
      Respiratory burst deactivated macrophages-mounted potent nitric oxide response,
      indicating that this deactivation event was selective for respiratory burst
      activity. Autocrine factors produced by MAF-activated macrophages augmented
      priming of the respiratory burst, suggesting that deactivation of primed
      respiratory burst responses was not due to cytokine mediators produced by
      activated macrophages, but was most likely an intracellular deactivation event.
      Furthermore, production of reactive intermediates by activated fish macrophages
      was biphasic; with maximal ROI production occurring 6 h after stimulus, and
      maximal RNI occurring 72 h after stimulus. Our results indicate that activated
      fish macrophages mount sequential antimicrobial responses that are selectively
      deprogrammed once maximal induction has occurred. The ability to selectively
      deactivate ROI production without affecting subsequent RNI production may play an
      important role in host defense: regulating the duration of ROI production, and
      thus minimizing host tissue damage in an otherwise futile attempt to eliminate
      ROI resistant pathogens.

PMID- 9040989
TI  - An approach to the design of novel cognitive enhancers using molecular modeling
      and X-ray crystallography.
AB  - A novel series of cognition enhancers was designed based on molecular modeling
      and X-ray structure analysis of EXP-9121 (2). This new series features a
      spirocyclic ring system that constrains the side chain substituents into the
      orientation seen in the X-ray crystal structure of 2. MM2 calculations preformed
      on 2 accurately predicted the solid state conformation. Compounds could be
      rapidly assembled using a bis-Michael addition reaction. Unfortunately, in vitro
      testing showed moderate activity at best, suggesting the X-ray structure of 2
      does not mimic the bioactive conformation.

PMID- 9040990
TI  - Predictive quantitative structure-activity relationships (QSAR) analysis of beta
      3-adrenergic ligands.
AB  - A novel quantitative structure-activity relationships strategy was used to
      analyze seventeen beta-adrenergic ligands for which we had previously evaluated
      pharmacological properties in Chinese hamster ovary cells transfected with the
      human beta 1-, beta 2- or beta 3-adrenergic gene (Blin et al., 1993, Mol.
      Pharmacol., 44: 1094-1104). These ligands were classified into pharmacological
      activity categories in order to determine the extent to which molecular
      structural features may be involved in the selectivity of the interaction with
      the beta 3-AR, or to define molecular features and properties characteristic of a
      beta 3-AR high affinity ligand or of a potent beta 3-adrenergic agonist.
      Topological and physico-chemical molecular descriptors were obtained using a
      novel software combining calculations with multivariate statistical methods, such
      as principal component analysis and discriminant analysis. This study showed that
      beta 1/beta 2-antagonists beta 3-agonists could be differentiate from beta 1/beta
      2/beta 3-agonists on the basis of their topological molecular descriptors
      weighted by partial atomic charge and lipophilicity logP values. Bulky lipophilic
      groups at the end of the alkylamine chain and an ethoxy function, extending the
      flexible portion of the molecule and modifying the electron density distribution,
      were requirements for selective agonism at the beta 3-site. Charge and logP
      weighted 2D-autocorrelation vectors were properties able to discriminate between
      classes of agonists in terms of their affinity, potency or intrinsic activity,
      thus emphasizing the part these molecular descriptors play in determining beta 3
      adrenergic ligands. These results, in association with the powerful activity
      prediction model evaluated in the test, provide a framework to rationalize the
      synthesis of new beta 3-AR specific compounds.

PMID- 9040983
TI  - Cloning and recombinant expression of a barred sand bass (Paralabrax nebulifer)
      cDNA. The encoded protein displays structural homology and immunological
      crossreactivity to human complement/cofactor related plasma proteins.
AB  - A new cofactor related cDNA in the bony fish Paralablax nebulifer, (barred sand
      bass) was isolated from a sand bass liver cDNA library. The clone (c71) is 1040
      bp in size and the predicted translation product of 204 amino acids contains a
      hydrophobic signal peptide, which is followed by a region of three short
      consensus repeats (SCRs). The three SCRs display high homology to SCRs of the 110
      kDa chain of the sand bass plasma cofactor protein, and to a lesser degree to
      human complement factor H related protein 3 (FHR-3) and to human factor H.
      Recombinant expression of the c71 cDNA in the baculovirus system shows a product
      of an apparent molecular mass of 27 kDa, which is secreted and glycosylated. It
      also contains a His-tag for purification purposes. Removal of the His-tag yields
      a 24 kDa protein, and deglycosylation further reduces the molecular mass to 21
      kDa. This size is in agreement with the calculated molecular mass based on amino
      acid composition. The sand bass SBCFR-1 protein is immunologically related to the
      human complement proteins, factor H and factor H-related protein 3. The
      recombinantly expressed protein reacted with antisera against the human FHR-3
      protein and SCRs 19-20 of human factor H. The presence of SCR-containing proteins
      in sand bass plasma and their structural and immunological homology to human FHR
      3 and factor H suggests for a common function between these evolutionary related
      proteins.

PMID- 9040986
TI  - Identification of a T lineage antigen in the catfish.
AB  - A murine monoclonal antibody produced against catfish thymocytes and
      immunoglobulin-negative lymphocytes in the blood identified a catfish T cell
      antigen designated CfT1. The CfT1 antigen was found to be expressed on
      thymocytes, a subpopulation of the lymphoid cells in blood and other lympho
      hemopoietic tissues, and a T cell line, but was not expressed by erythrocytes,
      thrombocytes, myeloid cells, B cells or macrophage cell lines. Stimulation of
      blood mononuclear cells with the T cell mitogen, concanavalin A, resulted in an
      increased frequency of CfT1+ cells. Conversely, lipopolysaccharide stimulation
      increased the number of IgM+ B cells and decreased the frequency of CfT1+ cells.
      The CfT1 antigen was defined as a single chain protein of M(r) 35,000 lacking N-
      and O-linked sugars. The CfT1 molecule thus provides a T lineage-specific marker
      in this bony fish representative.

PMID- 9040991
TI  - Effects of substituent size upon adenosine receptor A1/A2 affinity of some newly
      synthesised 8-cycloalkyl xanthines.
AB  - The activity of a series of 1,3-dipropyl-xanthines bearing C8-cycloalkyl
      substituents as antagonists at A1 and A2 adenosine receptors is examined.
      Pharmacological results showed that the size of the 8-substituent is an important
      feature for response in activity of such class of antagonists. Among compounds 3
      8, the 2-norbornyl analog 6 showed the best A1/A2 selectivity. A new route for
      the synthesis of 8-alkyl-substituted xanthines is presented. This method,
      consisting of a direct alkylation of the imidazole moiety through a radical
      mechanism reaction, was shown to be a more convenient strategy in comparison with
      the commonly employed synthetic schemes.

PMID- 9040997
TI  - A prospective evaluation of the endoscopic spectrum of overtube-related
      esophageal mucosal injury.
AB  - BACKGROUND: Placement of an overtube is required for endoscopic variceal
      ligation. The spectrum of overtube-related esophageal mucosal injury is unknown.
      We made a prospective comparison of two types of overtubes and a determination of
      the frequency, severity, and risk factors for overtube-related injury. METHODS:
      Two overtubes (60F, 20 cm, "new" overtube; and 60F, 25 cm, "old" overtube) were
      used and placed using the bougie-assisted technique. Mucosal integrity was
      documented before and after variceal ligation. Overtube contact time, bands
      number, setting (emergent versus elective), type of overtube, degree of
      coagulopathy, and development of symptoms after variceal ligation were recorded.
      RESULTS: Fifty sessions in 29 patients were analyzed; 24% of sessions were
      emergent. The old overtube was used in 24 sessions and the new in 26. Mucosal
      injury occurred in 72% of sessions. Mean overtube contact time was 11.58 +/- 0.97
      minutes, the mean number of bands placed per session was 6.4 +/- 0.4, and the
      mean international normalized ratio was 1.47 +/- 0.06. No risk factors correlated
      with mucosal injury except for the old overtube, which was associated with tears
      (p = 0.02). CONCLUSIONS: Mucosal injury related to the overtube is frequent but
      clinically unimportant. Because mucosal tears occurred significantly more often
      with the old overtube, we suggest that its use should be avoided.

PMID- 9040994
TI  - In vitro evaluation of wire integrity and ability to reprocess single-use
      sphincterotomes.
AB  - BACKGROUND: Sphincterotomes are currently marketed as one-time-use items and
      constitute considerable cumulative expense in a busy endoscopy unit. It is
      uncertain whether these accessories can be safely reprocessed without loss of
      form and function. METHODS: We studied disposable sphincterotomes (five 5F, five
      6F) in vitro as to their durability, electrical integrity, and ability to be
      adequately cleaned both manually and with ethylene oxide after contamination with
      10(5) to 10(6) Mycobacterium chelonei. RESULTS: Seven of the 10 sphincterotomes
      withstood the rigors of reuse; three 6F sphincterotomes developed wire fracture
      between four and eight uses. Electrical integrity, as measured by an
      electrosurgical analyzer, remained intact up to time of breakage in all
      sphincterotomes. Manual cleaning followed by glutaraldehyde soak resulted in
      residual mycobacterial colonies in five 6F sphincterotomes and a single 5F
      sphincterotome. No instrument had residual organisms cultured following manual
      cleaning and ethylene oxide sterilization. CONCLUSIONS: The authors conclude that
      one-time-use sphincterotomes have the potential for safe reuse.

PMID- 9040992
TI  - Design, synthesis and biological evaluation of benzoic acid mustard derivatives
      of imidazole-containing and C-terminal carboxamide analogues of distamycin.
AB  - The synthesis, DNA binding and biological evaluation of two benzoic acid mustard
      derivatives of imidazole-containing analogues of distamycin in which the C
      terminus is modified to contain a terminal carboxamide are described. The
      apparent DNA binding constants of compounds 5 and 6 were determined using an
      ethidium displacement assay, and the results showed that they do not have the AT
      sequence selectivity of distamycin and they show an acceptance for GC base pairs.
      Based on their pronounced binding to T4 DNA the data suggest that they bind to
      the minor groove of DNA. The cytotoxicities of compounds 5 and 6 in human chronic
      myeloid leukemia cells were determined using a MTT assay, and their IC50 values
      were 27 and 16 microM, respectively, and higher than the corresponding non
      terminal carboxamide-containing analogues 3 and 4. Both compounds were however
      markedly more active than the non-targeted mustard BAM [N,N-bis (-2-chloroethyl)
      4-aminobenzoic acid]. In the NCI panel of cell lines 5 gave a distinctly
      different pattern of tumor selectivity from 6. While these compounds were shown
      to alkylate DNA using a CD alkylation assay (35 +/- 10% for 5 and 85 +/- 10% for
      6), they produced interstrand crosslinks poorly, even at 100 microM drug
      concentrations. Based on preliminary data from a polymerase stop assay compounds
      3-6 gave different patterns of sequence selection monoalkylation which may
      contribute to their differing biological activities.

PMID- 9040993
TI  - Molecular geometries of dibenzothiazepinone and dibenzoxazepinone calcium
      antagonists.
AB  - A number of dibenzothiazepinones and dibenzoxazepinones have been designed,
      synthesized and evaluated as calcium antagonists. Molecular geometries of these
      dibenzotricyclic calcium antagonists have been studied using X-ray
      crystallography, molecular modeling and two-dimensional NMR spectroscopy. X-Ray
      diffraction reveals dibenzothiazepinone 1 and dibenzoxazepinone 2 to have,
      respectively, flexure angles of 108 degrees and 116.9 degrees between the two
      benzene rings. The molecular mechanics-optimized geometry of dibenzothiazepinone
      1 shows a 7 degrees smaller flexure angle than the X-ray crystallographic result,
      while that of dibenzoxazepinone 2 has an angle only 2 degrees smaller than the X
      ray result. AM1 and ab initio calculations show that the side chains can affect
      the geometry of the tricyclic nucleus and both 1 and 2 have negative
      electrostatic potentials around the bridged portion of the tricyclics. Two
      dimensional NOESY NMR spectroscopy supports the extended geometry of the 6 carbon
      spacer as obtained from X-ray crystallography and molecular mechanics
      calculations. Vasorelaxation properties among these compounds appear to be
      relatively insensitive to the flexure angle and to chain length. Vasorelaxation
      is profoundly influenced by the nature of the basic terminal moiety.

PMID- 9040995
TI  - A prospective study of the repeated use of sterilized papillotomes and retrieval
      baskets for ERCP: quality and cost analysis.
AB  - BACKGROUND: The impact on instrument quality and cost of the practice of reusing
      ERCP accessories has not been fully addressed. METHODS: Twenty-five new
      papillotomes and 15 new retrieval baskets were labeled and evaluated over time by
      staff blinded to the number of prior uses. Instruments were scored as to their
      function for the designated task. The cost of this practice was calculated from
      the purchase price of accessories and the costs of cleaning, sterilization, and
      disposal, and then compared with the estimated cost of a practice of one-time use
      of similar instruments. RESULTS: Twenty-five papillotomes were used 246 times
      (median 8; mean 9.8). Fifteen retrieval baskets were used 193 times (median 13;
      mean 12.9). The median survival of both papillotomes and baskets before being
      considered inadequate (score < 6 out of 10) was 9 uses. There were no
      complications attributable to using reused equipment. The projected yearly cost
      savings of using reusable versus disposable instruments was $94,095 for
      papillotomes and $61,809 for baskets, a 475% and 322% cost reduction,
      respectively. CONCLUSION: The papillotomes and baskets in this study could be
      reused reliably and safely multiple times, with considerable cost savings
      compared with the practice of using disposable instruments.

PMID- 9040996
TI  - A new system for defining endoscopic complications emphasizing the measure of
      importance.
AB  - BACKGROUND: Currently, there are no satisfactory systems for defining,
      classifying, and/or scoring endoscopic complications, although it would be
      important for quality assurance, comparative studies, and outcomes research.
      Recently the term "negative outcomes" was proposed rather than "complications,"
      and an approach that incorporates "measures of importance" was added to compare
      negative outcomes. METHODS: A system was developed that defines, classifies, and
      grades negative outcomes with a scoring system based on measures of importance.
      Information was recorded on a Morbidity and Mortality (M & M) form, which was
      used at a monthly quality assurance (M & M) conference. Several measures of
      importance related to the immediate negative outcome (O) were quantified (effect
      of the complication on completion of the endoscopy, change in level of care,
      change in number of hospital days, necessity for new invasive procedures). The
      disability (D), defined as a residual or chronic negative outcome caused by the
      complication, was characterized and scored. Death (D) was also characterized, the
      value varying with circumstances. As a quantitative measure, an overall ODD score
      was used. RESULTS: One hundred twenty-three negative outcomes were
      retrospectively classified using the new M & M form and the ODD score was applied
      for 117 complications. Complications were ranked according to the ODD score.
      CONCLUSION: A system for defining, classifying, and grading negative outcomes of
      endoscopic procedures is proposed with a quantitative scoring system that
      emphasizes measures of importance. The ODD score looks at the immediate negative
      outcome and also the separate long-term issues of disability and death.

PMID- 9040998
TI  - Radial scanning and linear array endosonography for staging pancreatic cancer: a
      prospective randomized comparison.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is known to be accurate for staging
      pancreatic cancer. Little data exist to determine if linear array or radial
      scanning EUS is superior for staging pancreatic cancer. This prospective
      comparison was undertaken to assess the accuracy of linear array and radial
      scanning EUS for staging pancreatic cancer. METHODS: Patients with pancreatic
      cancer referred for EUS staging were randomized to linear array or radial
      scanning EUS. Staging accuracy for each was determined by comparison to surgical
      pathology in those patients going to surgery. RESULTS: Seventy-nine patients with
      pancreatic cancer were enrolled and 33 had surgical resection. Of these, 17
      patients were randomized to linear array and 16 to radial scanning EUS. The
      remaining 46 patients did not have surgery because of comorbid illness or
      clinically unresectable disease. EUS staging accuracy for linear array was 94%
      (16 of 17) for T and 71% (12 of 17) for N staging, whereas radial scanning was
      88% (14 of 16) for T and 75% (12 of 16) for N staging. For predicting vascular
      invasion, radial scanning was 100% accurate (16 of 16) while linear array was 94%
      (16 of 17) accurate. There was one false-negative assessment of invasion using
      linear array EUS. CONCLUSION: Overall, both EUS designs appear equivalent for
      staging pancreatic cancer and assessing vascular invasion. In view of our
      findings and the capability for ultrasound-directed fine-needle aspiration with
      linear array EUS, this instrument may be the preferred choice for evaluating
      pancreatic masses.

PMID- 9040999
TI  - Endoscopic ultrasonography for diagnosing choledocholithiasis: a prospective
      comparative study with ultrasonography and computed tomography.
AB  - BACKGROUND: We assessed the diagnostic usefulness of endoscopic ultrasonography
      (EUS) for choledocholithiasis. METHODS: A prospective series of 155 patients with
      suspected choledocholithiasis all underwent EUS, conventional ultrasonography,
      CT, and ERCP. In 142 patients with a clear cholangiogram on ERCP, we analyzed the
      capability of EUS to image the extrahepatic bile duct and to identify
      choledocholithiasis, compared with ultrasonography and CT. RESULTS: No
      complications were encountered in performing EUS. In 51 patients, ERCP
      demonstrated bile duct stones, which were confirmed at endoscopic sphincterotomy
      or surgery. The extrahepatic bile duct was wholly displayed in 96% by EUS, in 60%
      by ultrasonography, and in 80% by CT. EUS (96%) was more sensitive than
      ultrasonography (63%) and CT (71%) for detecting choledocholithiasis (p < 0.001).
      Although ultrasonography and CT were poorly diagnostic for choledocholithiasis in
      patients with small stones or those with a nondilated common bile duct, EUS was
      able to accurately detect choledocholithiasis regardless of the size of stones or
      the diameter of the bile duct. The specificity of EUS (100%) was higher than
      those of ultrasonography (95%) and CT (97%). CONCLUSIONS: EUS, a safe imaging
      procedure, is more accurate than ultrasonography and CT and may be as accurate as
      ERCP for diagnosing choledocholithiasis.

PMID- 9041000
TI  - Endoscopic ultrasound staging criteria for esophageal cancer.
AB  - BACKGROUND: Malignant esophageal masses can be staged with endoscopic ultrasound
      (EUS) using the TNM staging classification. Several criteria for differentiating
      between intraesophageal (T1-2) and extraesophageal (T3-4) masses have been
      described, but highly accurate staging remains difficult. METHODS: This is a
      blinded evaluation of four specific EUS criteria in 24 patients with esophageal
      malignancy who underwent esophageal resection after neoadjuvant chemotherapy.
      Radial EUS was used to evaluate the first 12 patients and curved linear EUS was
      used in the second half of the group. Using the histology of the resected
      specimens, the sensitivity, specificity, and accuracy of the EUS criteria after
      chemotherapy were determined for predicting intraesophageal or extraesophageal
      invasion. RESULTS: There was no difference in the accuracy rates with radial or
      linear EUS. Two ultrasound criteria, muscularis disruption and irregular mass
      border, were found to have low accuracy rates (44% and 50%). The maximal
      thickness (overall or extraesophageal) of the esophageal mass was found to be
      highly accurate (79% and 87%) in predicting intraesophageal or extraesophageal
      extension. pT3-4 masses had a thickness of 16.0 +/- 2 mm, significantly greater
      than pT1-2 masses, 8.2 +/- 1 mm (p < .01). Using receiver operator
      characteristics (ROC) curve analysis, mass thickness was found to be more
      accurate (91% and 94%) than a subjective assessment of staging (73%) (p < .07).
      CONCLUSIONS: The EUS measurement of a malignant esophageal mass maximal thickness
      can accurately predict extraesophageal extension.

PMID- 9041001
TI  - Long-term safety of India ink tattoos in the colon.
AB  - BACKGROUND: When the India ink tattoo is used as a guide for follow-up
      examinations, the tattoo may remain in the colon for the remainder of that
      patient's life. This raises the question of the long-term safety of India ink
      tattoos. The long-term clinical and histologic consequences of the tattoo have
      not been studied in a large group of patients. METHODS: Biopsy specimens were
      taken from all tattoo marks encountered during postpolypectomy surveillance
      colonoscopy in 55 patients. Seventeen of these patients were followed serially
      with two biopsies in 16 patients and three biopsies in 1 patient. A total of 74
      biopsy specimens were obtained from tattoos that had been placed an average of 36
      months prior to biopsy (range 1.5 to 117 months). RESULTS: There were no clinical
      complications such as infection, fever, or abdominal pain in any of the 55
      patients. There were no endoscopic abnormalities on or adjacent to the tattoos.
      There were no histologic changes seen at the tattoo sites in 48 patients, mild
      chronic inflammation in 6 patients, and hyperplastic change in 1 patient. There
      were no neoplastic changes of the mucosa overlying the tattoo. CONCLUSIONS: Small
      volume India ink tattooing of the colon appears to remain endoscopically
      identifiable over a long term and to be safe based on histologic analysis of
      sequential biopsies.

PMID- 9041003
TI  - Enteroscopy-enteroclysis: experience with a combined endoscopic-radiographic
      technique.
AB  - BACKGROUND: Video enteroscopy provides high-quality diagnostic and therapeutic
      capabilities in the proximal small bowel. Enteroclysis remains an essential
      diagnostic technique in the distal small bowel. We report our experience with the
      combination of these techniques. METHODS: Seventy-one patients with obscure
      gastrointestinal bleeding (group A, 54 patients) or abnormal radiologic studies
      (group B, 17 patients) were evaluated with enteroscopy. Enteroclysis via a tube
      inserted on withdrawal of the enteroscope was performed in all patients with
      nondiagnostic enteroscopy. RESULTS: Enteroscopy identified bleeding sites in 29
      of 54 (54%) group A patients (12 angiodysplasia, 10 ulcers, 7 gastric erosions, 1
      vessel, 1 aortoenteric fistula), and lesions in 11 of 17 (65%) group B patients
      (7 ulcers, 3 benign strictures, 2 radiation enteritis, 1 mass). In group A, 13
      (24%) patients had findings detectable by standard esophagogastroduodenoscopy.
      Enteroclysis identified masses in 2 of 24 (8%) group A patients, and lesions in 5
      of 10 (50%) group B patients (3 strictures, 1 mass, 1 large diverticulum). No
      complications occurred. CONCLUSIONS: The combination of enteroscopy and
      enteroclysis is safe and offers quality small bowel examinations in more
      comfortable and convenient single diagnostic sittings. This combination detected
      bleeding sources in 57% and lesions in 70% of patients. Though enteroclysis
      identified bleeding sources in only 8% of patients, this study excluded lesions
      other than angiodysplasia.

PMID- 9041002
TI  - Resolution of chronic anal fissures after treatment of contiguous internal
      hemorrhoids with direct current probe.
AB  - BACKGROUND:  PURPOSES: (1) to prospectively evaluate efficacy and safety of
      direct current (DC) probe treatment of chronic anal fissures associated with
      internal hemorrhoids, and (2) to estimate direct and indirect costs of anoscopic
      treatment versus surgery. METHODS: Ten patients with chronic fissures of 11 mm
      (mean length) had symptoms for 5 months (mean) in spite of medical management;
      all had internal hemorrhoidal disease. DC coagulation was applied to two or three
      contiguous internal hemorrhoids per outpatient session. Eleven mA (mean) of DC
      current was delivered for 7 minutes (mean) per hemorrhoid segment. RESULTS: All
      10 patients had relief of chronic anal pain within two treatments and nine anal
      fissures healed within 4 weeks. One patient developed a perianal abscess and
      fistula requiring surgery. There were no recurrences in 20 months (mean) of
      follow-up with medical management. Mean direct and indirect costs (in terms of
      lost time from work or usual activity) of DC probe treatments were estimated to
      be 10% to 30% lower and 2 to 10 times less, respectively, than standard surgery
      for chronic anal fissures. CONCLUSION: DC probe treatment for chronic anal
      fissures associated with internal hemorrhoidal disease is an important advance as
      an effective, safe, and cost-effective nonsurgical treatment in selected
      patients.

PMID- 9041004
TI  - Disease stage of chronic hepatitis C assessed by both peritoneoscopic and
      histologic findings and its relationship with response to interferon therapy.
AB  - BACKGROUND: Disease stage in patients with chronic hepatitis C was assessed by
      both peritoneoscopy and histology and correlated with responses to interferon
      therapy. METHODS: The subjects were 105 patients with chronic hepatitis C treated
      with interferon who were classified into 28 sustained responders, 34 transient
      responders, and 43 nonresponders according to alanine aminotransferase
      normalization. The influence of various patient's characteristics on responses to
      interferon therapy was investigated by multivariate analysis. RESULTS: Patients
      were categorized into 21 patients who exhibited a "smooth liver" on
      peritoneoscopy and did not demonstrate histologic bridging fibrosis (group I) and
      84 patients who exhibited a "granular" or "nodular liver" on peritoneoscopy
      and/or had histologic bridging fibrosis (group II). Multivariate analysis showed
      that genotype 2a/2b (p = .0002), low viremia (p = .0048), and early disease stage
      (group I) (p = .0290) were significant independent factors contributing to
      sustained response, and that early disease stage (group I) (p = .0010) and
      genotype 2a/2b (p = .0085) were those contributing to sustained or transient
      response. Neither peritoneoscopic nor histologic findings alone were a
      significant factor influencing responses to interferon therapy. CONCLUSION:
      Disease stage assessed by both peritoneoscopic and histologic findings may serve
      as a reliable marker for predicting responses to interferon therapy in chronic
      hepatitis C.

PMID- 9041005
TI  - Nonsurgical strictureplasty for intestinal strictures in Crohn's disease:
      preliminary report of two cases.

PMID- 9041006
TI  - Management of a refractory benign esophageal stricture with a new biodegradable
      stent.

PMID- 9041007
TI  - Endoscopic mucosal resection of gastric neoplasms using a ligating device.

PMID- 9041008
TI  - Fatal hepatic air embolism following ERCP.

PMID- 9041009
TI  - Combined percutaneous-endoscopic therapy for recurrent pancreatitis and pancreas
      divisum.

PMID- 9041010
TI  - Botulinum toxin injection for secondary achalasia with esophageal varices.

PMID- 9041011
TI  - Botulinum toxin injection for an esophageal muscular A-ring.

PMID- 9041012
TI  - Scurvy and the gastrointestinal tract.

PMID- 9041013
TI  - Colonoscopic red ring sign due to chronic lymphocytic leukemia.

PMID- 9041014
TI  - Colonic histoplasmosis in AIDS: unusual endoscopic findings in two cases.

PMID- 9041015
TI  - Preoperative diagnosis of cystic lymphangioma of the colon by endoscopic
      ultrasound.

PMID- 9041016
TI  - Early carcinoma of the gallbladder diagnosed by percutaneous cholecystoscopy.

PMID- 9041017
TI  - ERCP recycling.

PMID- 9041018
TI  - The ODD score: an opportunity to develop a definitive measure for assessing
      endoscopic outcomes.

PMID- 9041019
TI  - Pathologic definition of endoscopic resection specimens.

PMID- 9041020
TI  - Enteroscopy and cautery for small intestinal angiodysplasia.

PMID- 9041021
TI  - Tandem expandable stent technique for a fractured nitinol stent.

PMID- 9041022
TI  - Value of laparotomy in the diagnosis of obscure gastrointestinal haemorrhage.

PMID- 9041023
TI  - Photodynamic therapy for malignant tumours of the ampulla of Vater.

PMID- 9041024
TI  - Endoscopic papillectomy: a novel approach to difficult cannulation.

PMID- 9041039
TI  - Preparation and evaluation of polyurethane surfaces containing immobilized
      plasminogen.
AB  - Plasminogen has been immobilized onto a segmented polyurethane containing amino
      groups, using glutaraldehyde as coupling agent. It was also aspecifically
      adsorbed, for sake of comparison, onto polyurethane films containing different
      functional groups and, in particular, epsilon-amino caproic acid and lysine
      residues. The differently immobilized plasminogen has been converted to plasmin
      by activation with urokinase, and the percentage of active plasmin for the
      various polymer films was determined using a tripeptide (S-2251) as a synthetic
      substrate. The biological behaviour of the differently treated polymer films has
      been evaluated in vitro by measurements of partial thromboplastin time (PTT) and
      platelet adhesion.

PMID- 9041040
TI  - Poly(ethylene oxide)-modified carboxylated polystyrene latices--immobilization
      chemistry and protein adsorption.
AB  - alpha,omega-Diamino poly(ethylene oxides) (PEOs) with different molecular weights
      (148, 1000, and 3400) were covalently immobilized onto carboxylated polystyrene
      latices. The immobilization of PEO was carried out with N-(3-dimethylaminopropyl)
      N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) in aqueous media. The
      reaction conditions were optimized to obtain a maximal coupling of PEO. The
      degree of coupling was determined by the surface concentration of amino groups.
      The maximal surface concentrations of amino groups were close to what is expected
      for a complete coverage of the surface with PEO. Adsorption of albumin from a
      buffer solution onto PEO-containing surfaces was about 85% less than the albumin
      uptake by unmodified polystyrene latices. Protein adsorption from plasma
      dilutions was lower on surfaces containing PEO molecules with a higher molecular
      weight. The reduction of the protein uptake from plasma by surfaces containing
      PEO-3400 molecules was only 40% compared to the adsorption to unmodified
      surfaces. These results indicate that plasma proteins have a low affinity for
      surfaces modified with PEO. However the PEO modified surfaces are by no means
      'protein resistant' when exposed to plasma.

PMID- 9041041
TI  - Biological activity of maleic anhydride copolymers. I. Biocompatibility and
      antitumoural effects of maleic anhydride-vinyl acetate, maleic anhydride-methyl
      methacrylate and maleic anhydride-styrene copolymers.
AB  - A series of maleic anhydride (MA)-vinyl acetate (VA), MA-methyl methacrylate
      (MM), and MA-styrene (S) copolymers were prepared and characterized. On employing
      various amounts of initiator, maleic anhydride-vinyl acetate, methyl
      methacrylate, and styrene copolymers with molecular weights ranging between
      18,000 and 200,000 have been obtained. The in vivo and in vitro tests performed
      on K562 cellular cultures (human chronic myeloid leukemia) have shown that, as a
      function of the molecular weight, the synthesized copolymers demonstrate a 50% in
      vitro cytotoxicity and an average tumour regression of maximum 68%.

PMID- 9041042
TI  - Surface modification of chitosan membranes by complexation-interpenetration of
      anionic polysaccharides for improved blood compatibility in hemodialysis.
AB  - Chitosan membrane surface was modified by complexation and interpenetration of
      anionic polysaccharides--heparin and dextran sulfate--for improved blood
      compatibility in hemodialysis. Electron spectroscopy for chemical analysis
      results showed a characteristic sulfur (S) and sodium (Na) peaks after
      modification with dextran sulfate. The sulfur/carbon (S/C) atomic composition
      ratio increased from 0.03 to 0.08 when the bulk dextran sulfate concentration
      used for modification was increased from 2.5 to 10 mg ml-1. The permeability of
      urea and creatinine did not change significantly upon modification with heparin
      or dextran sulfate. Surface modification, however, did decrease the permeability
      coefficients of glucose, vitamin B-2, and vitamin B-12. Unlike Cuprophan,
      chitosan and surface-modified chitosan membranes did not significantly activate
      the complement system as measured by the serum iC3b concentration. Compared to
      forty and sixty fully-activated platelets present on control surfaces, surface
      modification with heparin and dextran sulfate significantly reduced the number of
      adherent platelets per 25,000 microns 2 area and the extent of platelet
      activation. Surface modification with anionic polysaccharides, however, did
      significantly shorten the plasma recalcification time leading to fibrin clot
      formation. The results of this study show that chitosan membrane surface can be
      modified by complexation-interpenetration of anionic modifying agents. The
      modified membranes do resist complement activation and platelet adhesion and
      activation.

PMID- 9041043
TI  - Fibronectin matrix formation by human fibroblasts on surfaces varying in
      wettability.
AB  - The spatial organization of extracellular fibronectin on biomaterial surfaces
      might be important for interaction with tissue cells. In previous investigations
      we have demonstrated that hydrophilic materials bind preadsorbed fibronectin that
      can easily be reorganized by fibroblasts in a specific matrix-like structure,
      while on less wettable materials (possessing water contact angles above 60 deg)
      the cells were unable to do this. As the cells continuously produce their
      fibronectin matrix, we tried in this study to answer the question of how the
      surface wettability of biomaterials influences the endogenous fibronectin matrix
      formation and its subsequent organization on the substrate. We cultured
      fibroblasts for 72 h on five different wettable surfaces: glass,
      aminopropyltriethoxysilane, pellethane, polyvinylchloride, and silicone, with
      water-contact angles gradually ranging from 25 to 105 deg. We demonstrated that
      the decreasing wettability of the materials significantly reduced endogenous
      fibronectin deposition on the substratum. Moreover, fibrillar organization of
      fibronectin appeared only on relatively hydrophilic glass and APS substrate,
      while on more hydrophobic materials like PVC and SI, cells secreted some
      fibronectin but were not able to organize it into a fibronectin matrix. These
      results were correlated with an altered cell morphology and spreading on these
      materials. In addition, an ELISA method has been implemented to quantify
      fibronectin matrix formation as a possible measure of the biocompatibility of
      materials, where a clear relation has been found between fibroblast growth and
      fibronectin matrix formation.

PMID- 9041044
TI  - Tolerogenic capacity of poly(ethylene glycol) (PEG)--modified ovalbumins in
      relation to their immunoreactivity towards anti-ovalbumin antibody.
AB  - Ovalbumin (OVA) was chemically modified with poly(ethylene glycol) (PEG)
      derivatives: activated PEG2, 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s
      triazine and activated PM13, copolymer of poly(oxyethylene) allyl methyl diether
      and maleic anhydride. Pretreatment of BALB/c mice with PEG2- or PM13-OVA
      suppressed the production of both IgG- and IgE-class anti-OVA antibodies induced
      by subsequent immunizations with unmodified OVA. PEG2-OVA had higher potency to
      suppress OVA-specific immune response than PM13-OVA. Although extensive
      modification (62%) of amino groups in the OVA molecule with activated PEG2 was
      required to diminish most of its immunoreactivity towards anti-OVA antibodies,
      only a low degree of modification (27%) was sufficient to induce tolerogenicity
      to OVA. Thus, the loss of immunoreactivity of PEG2-OVA was not prerequisite for
      its tolerogenic capacity. Moreover, the use of completely denatured PEG2-OVA
      immunogen lead to the loss of its ability to induce immune tolerance to native
      OVA. These observations are discussed in relation to the regulatory mechanism of
      immune response.

PMID- 9041045
TI  - Mathematical simulation of unidirectional tissue formation: in vitro
      transanastomotic endothelialization model.
AB  - In vitro transanastomotic endothelialization was studied using a mathematical
      model with the Fisher equation. The Fisher equation is a nonlinear parabolic
      equation which has a cell migration term and a population growth term. The
      mathematical model was used to simulate recent experiments performed to
      investigate quantitatively the unidirectional formation of a bovine endothelial
      cell monolayer in vitro. The two parameters included in the equation were
      estimated using a trial and error method in which the calculated solutions of the
      various values of the two parameters are compared with the experimental data and
      the best fit pair is adopted: one parameter, D, which represents the
      unidirectional cell migration rate and the other, k, which represents the
      population growth rate. The calculated solutions fit the experimental data well.
      We also simulated the healing of a mechanically disrupted endothelial monolayer
      sheet. The significance of cellular biomechanics in tissue formation and design
      of tissue-engineered devices is discussed.

PMID- 9041046
TI  - Cellular and molecular mechanisms of renal phosphate transport.

PMID- 9041048
TI  - Rapid protein kinase A--mediated activation of cyclic AMP-phosphodiesterase by
      parathyroid hormone in UMR-106 osteoblast-like cells.
AB  - Parathyroid hormone (PTH) plays an essential role in osteoblast proliferation and
      differentiation. The effects of PTH are known to be mediated by cyclic adenosine
      monophosphate (cAMP) and calcium and by the activation of protein kinase C (PKC).
      cAMP is hydrolyzed to the inactive form 5' AMP by cyclic nucleotide
      phosphodiesterases (PDEs). We have investigated the role of PTH on PDE regulation
      in UMR-106 osteoblast-like cells. Treatment with 10 nM PTH caused a 3-fold
      increase in the PDE activity. The activation of PDE could be seen within 2
      minutes and reached maximal levels after 20 minutes. The PTH effect was dose
      dependent with a half-maximal dose of 2 nM. The effect of PTH could be mimicked
      by the cAMP analogs Bt2 cAMP and forskolin, but not by PTH fragment 3-34, calcium
      ionophore A23187, or by the PKC activator phorbol 12-myristate 13-acetate. The
      PDE activity stimulated by PTH could be abolished by the PKA inhibitor H-8. The
      PDE activated by PTH was inhibitable by low concentrations of the cAMP-PDE
      specific inhibitor RO 20-1724 (IC50 = 0.2 microM), but not by low concentrations
      of the inhibitors of cGMP-stimulated and cGMP-inhibited PDEs MEP-1 and milrinone
      (IC50 for both compounds > 30 microM). The PTH-stimulated cAMP accumulation was
      potentiated about 7-fold in the presence of RO 20-1724. H-8 potentiated the PTH
      stimulated cAMP accumulation about 4-fold. Our results show that PTH rapidly
      stimulates the activity of cAMP-PDE in UMR-106 cells. The PDE activation involves
      cAMP and PKA. Inhibition of PKA can abolish the PTH-stimulated PDE activation and
      leads to increased accumulation of intracellular cAMP.

PMID- 9041047
TI  - Human stanniocalcin inhibits renal phosphate excretion in the rat.
AB  - Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes
      where it counteracts hypercalcemia by inhibiting gill calcium uptake and
      stimulating renal inorganic phosphate (Pi) reabsorption. Human STC (hSTC) has
      recently been cloned and sequenced and is highly homologous to the fish hormone
      at the amino acid level. The objective of this study was to examine the possible
      effects of hSTC on electrolyte homeostasis and renal function in the rat.
      Recombinant hSTC was expressed in bacteria and purified by metal-ion affinity
      chromatography and reverse-phase high performance liquid chromatography.
      Anesthetized animals were given bolus infusions of 1, 5, or 10 nmol hSTC per
      kilogram of body weight. Control animals received solvent alone. The most
      effective dosage was 5 nmol/kg, which caused significant reductions in both
      absolute and fractional phosphate excretion in comparison with control rats. The
      hSTC had no effect on the renal excretion of other ions, the glomerular
      filtration rate, renal blood flow, blood pressure, or plasma electrolytes (Na+,
      K+, Ca2+, Pi, Mg/+). The maximum effect of hSTC on phosphate excretion was
      observed 60-80 minutes postinjection. Lesser effects were obtained with higher
      and lower dosages of hormone. When renal cortical brush-border membrane vesicles
      were isolated from control and hormone-treated animals 80 minutes postinjection,
      the rate of Na+/Pi cotransport was found to be 40% higher in vesicles from
      hormone-treated animals (p < 0.01; 5 nmol hSTC/kg). Together, the renal clearance
      and membrane vesicle data indicate that hSTC participates in the renal regulation
      of Pi homeostasis in mammals.

PMID- 9041049
TI  - Establishment and characterization of conditionally immortalized stromal cell
      lines from a temperature-sensitive T-Ag transgenic mouse.
AB  - We established bone marrow stromal cell lines from a transgenic mouse that
      harbors a temperature-sensitive mutant of the simian virus 40-derived large T
      antigen under the control of a major histocompatibility complex (MHC) I promotor.
      These cell lines were screened for their ability to induce the formation of
      osteoclasts in a spleen cell/stromal cell coculture system. By means of this
      screen, five clones, referred to as marine bone marrow stromal clone 1 (mBMS-B1)
      mBMS-B2, mBMS-B14, mBMS-B18, and mBMS-B21, were selected for detailed
      characterization. Cell growth depends on culture conditions, i.e., cells grow at
      33 degrees C in the presence of murine interferon-gamma, whereas cell
      proliferation ceases at 39 degrees C. The phenotype of the cells is also
      correlated with the culture conditions because the osteoclast inductive capacity
      is only seen at 39 degrees C, indicating that the cells undergo differentiation
      when the transforming agent is inactivated. These conditionally immortalized
      stromal cells can be induced to express a variety of markers that are typical for
      mature osteoblasts, e.g., alkaline phosphatase activity and expression of
      functional parathyroid hormone receptor after stimulation with soluble osteogenic
      protein 1 (sOP-1). mRNA analysis revealed the expression and regulation of
      osteopontin, osteonectin, and collagen alpha 1(I) as well as the inducibility of
      osteocalcin upon treatment with sOP-1. The cells have the potential to form
      mineralized nodules in supplemented medium. We observed expression of vascular
      cell adhesion molecule-1, which is stimulated upon treatment of the cells with 1
      alpha,25-dihydrocholecalciferol after 4 days, indicating the presence of the
      receptor for this steroid. These cell lines represent a model to study mechanisms
      and factors involved in osteoblast differentiation.

PMID- 9041050
TI  - Osteoblastic proliferation in bone biopsies from patients with end-stage chronic
      renal failure.
AB  - Osteoblasts have traditionally been considered to be terminally differentiated
      cells and therefore unable to divide. Data in recent years, however, indicate
      that cellular differentiation does not usually preclude preservation of
      proliferative ability and that most differentiated cells are able to divide under
      adequate stimuli. The aim of this study was to assess whether cubic osteoblasts
      undergo proliferation during the formation phase of the remodeling cycle under a
      stimulus that increased bone turnover. For that purpose, the osteoblastic
      proliferation index (OPI) was analyzed by DNA image cytometry in transiliac bone
      biopsies from 33 patients with chronic renal failure (23 men, 10 women; mean age
      50.4 +/- 15.1 years) who have been classified into low (n = 13), normal (n = 15),
      and high (n = 15) bone turnover according to activation frequency (Ac.f). OPI was
      significantly higher (p < 0.002) in the high bone turnover group (13.90 +/-
      4.72%) compared with the low (2.38 +/- 4.13%) and normal turnover groups (2.84 +/
      4.04%). There was a positive correlation between OPI and the following
      histomorphometric parameters: bone formation rate, surface referent (r = 0.76, p
      = 0.00001), activation frequency (r = 0.73, p = 0.00001), mineral apposition rate
      (r = 0.73, p = 0.00001), bone formation rate, volume referent (r = 0.71, p =
      0.00001), and mineralizing surface (r = 0.62, p = 0.0001). This study shows that
      a rise in bone turnover is associated with a marked increase of bone-forming cell
      proliferation in patients with end-stage chronic renal failure. From this
      finding, it may be concluded that cubic osteoblasts do not behave as "terminally
      differentiated" cells in vivo, because a high proportion of them are still able
      to divide.

PMID- 9041051
TI  - Bilateral tibial marrow ablation in rats induces a rapid hypercalcemia arising
      from extratibial bone resorption inhibitable by methylprednisolone or
      deflazacort.
AB  - The goals of this study were to quantitate biochemical markers of bone metabolism
      on days 1-15 after bilateral tibial marrow ablation surgery in young adult rats
      and to determine the effect of a single dose of methylprednisolone (2 mg/kg) or
      deflazacort (2.5 mg/kg) given at the time of ablation. Unexpectedly, serum
      calcium levels rose to a maximum of 15.9 mg/dl on day 7 after marrow ablation and
      remained above normal through day 15. This increase was blocked by a single
      intramedullary injection of methylprednisolone or deflazacort immediately
      following ablation; however, the fact that both drugs produced a characteristic
      rapid 3- to 10-fold increase in the serum alpha 2-macroglobulin level
      demonstrates that the drugs rapidly reached the circulation. Both
      methylprednisolone and deflazacort also inhibited intramedullary deposition of
      collagen by 40-60% on day 7, a time near which operated control animals achieved
      maximal accumulation of new bone in this model. Histological comparisons among
      the three experimental groups were largely consistent with biochemical results.
      The urinary hydroxyproline/creatine ratio for the operated control group doubled
      on day 3 and then returned to presurgical levels on day 7 and later. The timing
      and size of the hydroxyproline/creatinine peak, as well as the fact that the
      intratibial osteoclastic response peaks on days 8-10 after ablation, suggests it
      results from extratibial bone resorption induced by marrow ablation. Consistent
      with this rationale, urinary calcium excretion in operated controls rose 9-fold
      from day 0 to day 3 and appeared to plateau over the period from day 3 to day 9,
      before returning to a near presurgical level on day 15. Elevated excretion of
      calcium noted on days 9-15 in deflazacort-treated animals, which occurs in the
      absence of a detectable increase in resorption marker hydroxyproline, may however
      be due to the known action of glucocorticoids in increasing kidney filtration of
      calcium. In summary, this is the first report to show that bilateral tibial
      marrow ablation in rats causes a rapid hypercalcemia and calciuria which is
      accompanied initially by a peak of bone resorption marker urinary hydroxyproline.
      We speculate that the source of calcium and hydroxyproline is extratibial
      osteoclastic bone resorption induced by circulating cytokines whose release from
      ablated tibias or osteoclastogenic action is inhibitable by methylprednisolone
      and deflazacort.

PMID- 9041052
TI  - Different responses of bone alkaline phosphatase isoforms during recombinant
      insulin-like growth factor-I (IGF-I) and during growth hormone therapy in adults
      with growth hormone deficiency.
AB  - We studied serum bone alkaline phosphatase (ALP) isoforms and other markers of
      bone turnover in growth hormone-deficient (GHD) adults (n = 22). The patients
      were followed during 1 week of insulin-like growth factor-I (IGF-I)
      administration, 40 micrograms/kg of body weight/day (n = 6), and during 24 months
      of growth hormone (GH) therapy, 0.125 IU/kg of body weight/week for the first
      month, and then 0.250 IU/kg of body weight/week (n = 20). Six ALP isoforms were
      separated and quantified by high-performance liquid chromatography: one
      bone/intestinal, two bone (B1, B22), and three liver ALP isoforms. At baseline,
      the mean levels of B1, B22, and osteocalcin were higher in GHD adults than in
      healthy adults. After 2 week of IGF-I administration and 1 month of GH therapy,
      only B1 was decreased. We suggest that the initial decrease of B1 during GH
      therapy could be an effect of endocrine IGF-I action mediated by GH. After 3
      months of GH therapy, both B1 and B2 increased as compared with placebo.
      Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), cross
      linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary
      pyridinoline cross-links/creatinine ratio increased during GH therapy. PICP
      increased significantly before bone ALP and osteocalcin, indicating early
      stimulation of type I collagen synthesis as previously demonstrated by in vitro
      models. Different responses of the bone ALP isoforms during IGF-I and during GH
      therapy suggest different regulations in vivo.

PMID- 9041053
TI  - Protein interactions during assembly of the enamel organic extracellular matrix.
AB  - Enamel is the outermost covering of teeth and contains the largest hydroxyapatite
      crystallites formed in the vertebrate body. Enamel forms extracellularly through
      the ordered assembly of a protein scaffolding that regulates crystallite
      dimensions. The two most studied proteins of the enamel extracellular matrix
      (ECM) are amelogenin and tuftelin. The underlying mechanism for assembly of the
      proteins within the enamel extracellular matrix and the regulatory role of
      crystallite-protein interactions have proven elusive. We used the two-hybrid
      system to identify and define minimal protein domains responsible for supra
      molecular assembly of the enamel ECM. We show that amelogenin proteins self
      assemble, and this self-assembly depends on the amino-terminal 42 residues
      interacting either directly or indirectly with a 17-residue domain in the
      carboxyl region. Amelogenin and tuftelin fail to interact with each other. Based
      upon this data, and advances in the field, a model for amelogenin assemblies that
      direct enamel biomineralization is presented.

PMID- 9041054
TI  - Regulation of interleukin-6 secretion from mononuclear blood cells by
      extracellular calcium.
AB  - Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone
      resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple
      myeloma and the enhanced osteoclastic activity seen in postmenopausal
      osteoporosis. We recently reported that the calcium concentration in plasma
      affects IL-6 secretion from mononuclear blood cells. To investigate the
      underlying mechanism, we have studied the effect of calcium on IL-6 formation in
      mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were
      given 1 g of calcium orally after overnight fasting. Plasma levels of ionized
      calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured
      after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased
      and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear
      blood cells drawn 4 h after calcium intake was increased 185% as compared with IL
      6 secretion from cells drawn just before calcium intake. In control experiments
      without calcium intake, there was no alteration in pCa2+ and no effect on IL-6
      secretion from mononuclear blood cells. In vitro studies revealed that
      stimulation of isolated mononuclear blood cells with physiological concentrations
      of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at
      1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment of the
      isolated mononuclear blood cells with PTH or calcitonin. These observations
      demonstrate that the plasma calcium concentration affects IL-6 secretion from
      mononuclear blood cells. The in vitro data indicate the involvement of a direct
      calcium sensing mechanism. These findings might have implications in
      hypercalcemia and should also be borne in mind when considering the role of
      cytokines in osteoporosis.

PMID- 9041055
TI  - Vitamin D receptor polymorphisms, bone mineral density, and bone metabolism in
      postmenopausal Mexican-American women.
AB  - Common polymorphisms in the vitamin D receptor (VDR) gene have been shown to
      correlate with bone mineral density (BMD). However, attempts to replicate the
      original findings in other populations have yielded variable results. These
      disparities may reflect ethnic or environmental differences in the expression of
      the VDR effect upon BMD. We examined a relatively ethnically homogeneous group of
      103 healthy postmenopausal Caucasian women of Mexican descent living in Northern
      California. We determined the VDR genotype and measured the BMD at the lumbar
      spine and femoral neck by dual-energy X-ray absorptiometry, as well as several
      biochemical indices of mineral metabolism. The prevalence of the BB genotype,
      associated in previous studies with the lowest BMD, was 8% and highly linked to
      the tt genotype. Absolute and age-adjusted BMD at both hip and spine showed a
      trend toward lower BMD in the BB, AA, and tt genotypes, but this trend did not
      achieve statistical significance. There were no consistent intergroup differences
      in change in BMD over 2 years of follow-up, nor in mean serum concentrations of
      25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, or total urinary
      pyridinolines. Intact parathyroid hormone concentrations were significantly
      higher in subjects with the AA genotype, with a trend toward higher values in
      those with the BB and tt genotypes as well. Our data suggest that there may be a
      decrease in BMD associated with the B, A, and t alleles, but the intergroup
      difference in BMD is 0.2-0.5 standard deviations (SD) at the lumbar spine and 0.3
      SD at the femoral neck, decreases that are smaller than previously reported.
      Given the relatively low prevalence of the BB/tt genotype in Mexican-American
      Caucasians, a larger sample would be required to detect a significant association
      between VDR alleles and differences in BMD of the magnitude suggested by our
      data. We conclude that a genotype effect of this magnitude, if present, would be
      clinically relevant, but the impact on BMD is too small to detect with
      statistical significance in a study of this size.

PMID- 9041056
TI  - Influence of the vitamin D receptor gene alleles on bone mineral density in
      postmenopausal and osteoporotic women.
AB  - It is well established that genetic factors contribute to bone turnover and bone
      density. Evidence exists suggesting that a major part of this genetic influence
      may be due to polymorphisms in the vitamin D receptor (VDR) gene. However, it is
      not clear whether the VDR genotype effect persists in elderly women. In the
      present study, the relationship between the BsmI, ApaI, and TaqI polymorphisms in
      the VDR gene, and the bone mineral density (BMD) at the lumbar spine, the femoral
      neck (FN), and the proximal radius was investigated in a large group of elderly
      women (75.5 +/- 5.0 years) of Caucasian origin and in 84 Type I osteoporotic
      women (66.6 +/- 8.4 years). We did not find a correlation between the VDR
      genotypes and BMD in elderly women. However, a significantly higher FN-BMD was
      observed in obese (body mass index [BMI] > 30 kg/m2) versus nonobese (BMI < 30
      kg/m2) women (p < 0.01). This relationship was observed for all BsmI genotypes.
      Furthermore, the FN-BMD of nonobese women with bb BsmI genotype was 5% higher
      than that of women with the BB genotype (p = 0.04). We conclude that the VDR gene
      polymorphisms influence the FN-BMD in nonobese postmenopausal women. In a second
      part of the study, possible correlations between the VDR gene polymorphisms and
      osteoporosis Type I were analyzed. Our data could not reveal any association
      between these parameters.

PMID- 9041057
TI  - Determinants of radial bone density as measured by PQCT in pre- and
      postmenopausal women: the role of bone size.
AB  - The aim of the present study was to examine the influence of anthropometric,
      hormonal, and geometric factors on the variability of radial bone mineral density
      (BMD) in women. In 583 healthy pre- and postmenopausal females (aged 40-60 years)
      radial total (BD) and trabecular BMD (TBD) was measured by peripheral
      quantitative computerized tomography at the nondominant distal forearm. In
      addition, 29 women who had suffered a Colles' fracture after minor trauma were
      also evaluated. There was no age-dependent change in radial BD and TBD before
      menopause. We found a negative correlation between BMD and age and years since
      menopause (YSM) in postmenopausal women (BD = 422.73 - 2.342 age - 6.308YSM; r =
      0.36, p = 0.0001, n = 128). The variation of YSM, body mass index (BMI), and age
      accounted for 20% of the variability of BD in postmenopausal women. In contrast,
      in premenopausal women, only 3% of the variability could be explained by
      anthropometric variables. Bone mineral content (BMC) and bone area, but not BMD
      at the distal radius, were significantly correlated to grip strength (r = 0.25, p
      = 0.006 for BMC, r = 0.26, p = 0.003 for area). The cross-sectional bone area of
      the CT slice showed a significant increase with aging (y = 263.02 + 1.25x; r =
      0.14, p = 0.0009). There was a strong negative correlation between bone area and
      BD and TBD (y = 516.04 - 0.668x; r = -0.57, p < 0.0001 for BD). If BMD is
      normalized for BA, variation is reduced by 32% (for BD) and 10% (for TBD),
      respectively. Women with Colles' fracture had a significantly lower TBD
      normalized for BA (fracture group [-0.71 +/- 0.88] vs. normals (0.03 +/- 0.99]; p
      = 0.00009). Our results show that YSM and BMI are predictors of postmenopausal
      BMD. However, radial BMD is influenced strongly by geometric variables such as
      cross-sectional bone area.

PMID- 9041058
TI  - High-impact exercise promotes bone gain in well-trained female athletes.
AB  - Maximizing peak bone mass, as well as reducing its loss after menopause, is
      important for the prevention of osteoporosis. One mode of activity, gymnastics
      training, invokes high impact loading strains on the skeleton which may have
      powerful osteogenic effects. To examine the role of athletic activity,
      specifically gymnastics, on bone mineral density (BMD) accretion, we monitored
      longitudinal changes in regional and whole body BMD in collegiate women gymnasts
      and competitive athletes whose skeletons are exposed to differential loading
      patterns: runners and swimmers. Two cohorts were studied. Cohort I = 26 gymnasts
      (19.7 +/- 1.2 years), 36 runners (21.1 +/- 2.7 years) and 14 nonathletic women
      (19.3 +/- 1.7 years) followed over an 8-month period. Cohort II = 8 gymnasts
      (18.9 +/- 1.1 years), 11 swimmers (20.0 +/- 2.3 years) and 11 nonathletic women
      (19.0 +/- 1.2 years) followed over a 12-month period. Lumbar spine (L2-4),
      femoral neck, and whole body BMD (g/cm2) were assessed by dual-energy X-ray
      absorptiometry. For cohort I, the percent change in lumbar spine BMD after 8
      months was significantly greater (p = 0.0001) in the gymnasts (2.8 +/- 2.4%) than
      in the runners (-0.2 +/- 2.0%) or controls (0.7 +/- 1.3%). An increase in femoral
      neck BMD of 1.6 +/- 3.6% in gymnasts was also greater (p < 0.05) than runners (
      1.2 +/- 3.0%) and approached significance compared with controls (-0.9 +/- 2.2%,
      p = 0.06). For cohort II, gymnasts gained 2.3 +/- 1.6% at the lumbar spine which
      differed significantly (p < 0.01) from changes in swimmers (-0.3 +/- 1.5%) and
      controls (-0.4 +/- 1.7%). Similarly, the change at the femoral neck was greater
      (p < 0.001) in gymnasts (5.0 +/- 3.4%) than swimmers (-0.6 +/- 2.8%) or controls
      (2.0 +/- 2.3%). The percent change in BMD at any site did not differ between
      eumenorrheic and irregularly menstruating athletes. These results indicate that
      bone mineral at clinically relevant sites, the lumbar spine and femoral neck, can
      respond dramatically to mechanical loading characteristic of gymnastics training
      in college-aged women. This occurred despite high initial BMD values and was
      independent of reproductive hormone status. The results provide evidence to
      support the view that high impact loading, rather than selection bias, underlies
      high BMD values characteristic of women gymnasts. Because all athletes underwent
      resistance training throughout the year of study, muscle strengthening activity
      did not appear to be a significant factor in the skeletal response observed in
      gymnasts. We conclude that activities resulting in high skeletal impacts may be
      particularly osteotropic for young women.

PMID- 9041059
TI  - A new method of bone tissue measurement based upon light scattering.
AB  - In recent years, time-resolved spectroscopy systems using near infrared pulsed
      laser have been applied to develop optical computed tomography. We applied this
      technique to measure the optical properties of osseous tissues. First, we
      gradually demineralized 10 mm blocks of bovine trabecular bone with EDTA,
      maintaining the absorption characteristics and structure but varying the
      hydroxyapatite content, thus creating specimens differing only in light
      scattering properties. We used computer densitograms to assess light penetration,
      and analyzed the correlation with bone mineral density (BMD) as with dual-energy
      X-ray absorptiometry scans. The light penetration increased with decreasing BMD.
      Second, using the above-mentioned pulsed laser time-resolved spectroscopy system,
      we investigated the correlation between the BMD and the time response waveforms
      of 10-mm blocks of bovine cortical bone, trabecular bone, and surrounding tissue
      as well as human trabecular bone. The human lumbar vertebral bone also displayed
      an inverse correlation between BMD and maximum light penetration and a positive
      correlation between BMD and peak time delay. This is the first demonstration of a
      correlation between BMD and light scattering properties showing that BMD can
      indeed be measured with light. Our results show the possibility of obtaining
      information on internal bone structure and composition in vivo through assessment
      of the waveforms obtained by a time-resolution system in the near infrared
      region.

PMID- 9041060
TI  - Prostaglandin E2 (PGE2) and risedronate was superior to PGE2 alone in maintaining
      newly added bone in the cortical bone site after withdrawal in older intact rats.
AB  - The objects of this study were (1) to determine the effects of risedronate (Ris)
      and prostaglandin E2 (PGE2) alone and in combination, on tibial diaphyses of
      older intact female rats; and (2) to observe the fate of any extra bone if formed
      after withdrawal of the treatment. Nine-month-old female Sprague-Dawley rats were
      treated with 6 mg of PGE2/kg/day, 1 or 5 micrograms of Ris/kg twice a week, or 6
      mg of PGE2/kg/day plus 1 or 5 micrograms of Ris/kg twice a week for the first 60
      days and followed by vehicle injections for another 60 days. Cross-sections of
      double fluorescent labeled, undecalcified tibial diaphyses proximal to the
      tibiofibular junction were processed for histomorphometry. We found that: (1)
      neither the 1 microgram nor the 5 micrograms of Ris treatment in the 60-day on/60
      day off group showed any histomorphometric differences from age-related controls;
      (2) while the 60 days of PGE2 treatment added extra cortical bone (6%) on the
      tibial shaft (due to stimulation of periosteal, endocortical, and marrow
      trabecular bone formation), the new endocortical and most of the new marrow
      trabecular bone were lost when treatment was withdrawn; however, the new
      periosteal bone remained; (3) PGE2 with Ris added the same amount of new bone to
      tibial diaphysis as did PGE2 alone and upon withdrawal, new marrow trabecular
      bone was lost but new periosteal and endocortical bones were preserved in PGE2 +
      1 microgram of Ris on/off group. In contrast, all the new bone was maintained in
      the PGE2 + 5 micrograms of Ris on/off group; (4) PGE2 + Ris cotreatment failed to
      block the increase in cortical bone porosity induced by PGE2; and (5) in the PGE2
      alone and PGE2 + 1 microgram of Ris on/off groups bone turnover was higher than
      that in the PGE2 + 5 micrograms of Ris on/off group. These results indicate that
      on/off treatment with PGE2 and Ris is superior to PGE2 alone in that it forms the
      same amount of new bone during treatment, but preserves more cortical bone during
      withdrawal. Depression of bone resorption and turnover were the tissue mechanisms
      responsible for this protection.

PMID- 9041061
TI  - Prostaglandin E2 increases the skeletal response to mechanical loading.
AB  - The study tested the influence of prostaglandin E2 (PGE2) on the skeletal
      response to increased in vivo mechanical loading through a four-point bending
      device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/-
      34 g) were divided into 12 groups to accommodate all possible combinations of
      doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats
      received subcutaneous injections of PGE2 daily and in vivo loading of the right
      tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric
      analysis of the periosteal and endocortical surfaces following in vivo dual
      fluorochrome labeling was performed on both the loaded region of the right tibial
      diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the
      threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu
      epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the
      endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone
      formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined
      with the minimum effective load, an additive effect of PGE2 and loading on bone
      formation was observed at the endocortical surface, but a synergistic effect was
      noted at the periosteal surface. No combined effect of ineffective doses of
      loading and PGE2 was found. A synergistic effect at peak strains of approximately
      1625 mu epsilon on the periosteal surface could suggest either the involvement of
      locally produced growth factors or autoregulation of endogenous synthesis of PGE2
      by exogenously administered PGE2.

PMID- 9041062
TI  - Bone mineral density and blood flow to the lower extremities: the study of
      osteoporotic fractures.
AB  - This study tests the hypothesis that reduced blood flow to the lower extremities
      may affect bone remodeling, resulting in a decrease in bone mineral density
      (BMD). BMD was measured in the axial and appendicular skeleton of 1292 elderly
      women (mean age, 71 years) enrolled in the Study of Osteoporotic Fractures. The
      ratio of the posterior tibial and brachial systolic blood pressures, the
      ankle/arm index, was used as a measure of blood flow to the legs. In the cross
      sectional analysis, this index was positively correlated with BMD at the radius,
      calcaneus, and hip, but not at the spine. A decrease in the index of 2 standard
      deviations (SD) (as might occur in patients with moderate arterial disease) was
      associated with a decrease of 3.7% (95% CI, 1.7%, 5.8%) in hip BMD. The effect
      size at the hip decreased from 3.7 to 1.8% (and was not statistically
      significant) when adjustment was made for smoking and/or body mass index (BMI).
      In the prospective analysis, the rate of bone loss at the hip and calcaneus was
      greater (p < 0.05) among women whose annual decrease in ankle/arm index was more
      than 1 SD greater than the mean decrease. This increase was independent of
      estrogen use, smoking, BMI, pattern of fat distribution, history of diabetes,
      exercise, and ability to walk. The results from this prospective community-based
      study provide the first evidence that among relatively healthy older women
      decreased vascular flow in the lower extremities may be associated with an
      increased rate of bone loss at the hip and calcaneus.

PMID- 9041064
TI  - Anion effects on calcium metabolism.

PMID- 9041063
TI  - Degradable bisphosphonate-alkaline phosphatase-complexed hydroxyapatite implants
      in vitro.
AB  - Degradable hydroxyapatite (HA) implants complexed with the resorption inhibiting
      agent bisphosphonate (PCP) and the mineralizing agent alkaline phosphatase (ALP)
      can theoretically maintain alveolar bone mass directly after extraction of teeth.
      The present in vitro study investigated the surface properties of PCP-ALP
      complexed HA implants in relation to the requirements of implant behavior and
      action. Adsorbed PCP (pH 3.49) resulted in a flattening and broadening of the
      phosphate peaks and the formation of carbonate peaks in the HA pattern of the
      implant indicating a chemical alteration of the HA surface. Adsorption of ALP
      onto PCP-altered HA surfaces was 26% lower than onto HA implant blank surfaces.
      PCP-ALP-complexed HA implants released the PCP and ALP steadily and continuously
      over observation periods of, respectively, 75 and 14 days. During these
      observation periods, the ceramic grains of the HA implant became smaller and
      intergrain boundaries became broader. These morphologic characteristics suggested
      preconditioning of the HA implant surface for future bonding and degradation in
      vivo. Individual grains were no longer bonded to other grains and detached from
      the implant which had become rounded in shape. From in vitro mice experiments we
      found that PCP concentrations between 10(-4) and 10(-3) M resulted in 45Ca
      release from the bone HA. Our calculations showed, however, that only a total
      concentration of 1.4 x 10(-4) M PCP was gradually released over the whole
      observation period. In another experiment, it appeared that a PCP concentration
      in solution < 10(-3) M did not reduce ALP activity. It is concluded that release
      of PCP by the PCP-ALP-complexed implants is maintained at levels in the range to
      impair osteoclast bone resorption but not high enough to block osteoblast
      activity. The amount of ALP released can lead to induction of bone formation onto
      implant surfaces. pH-induced alterations in the microstructure and chemistry of
      the HA surface allow for controlled degradation of the HA implants in vitro. A
      PCP-ALP-complexed HA implant acting as temporary scaffolding for alveolar bone
      growth enhancement, mineralization, and maintenance seems to be a reasonable
      concept for preservation of the edentulous alveolus.

PMID- 9041065
TI  - A North American survey of educational background and job responsibilities of
      cardiopulmonary rehabilitation program directors.

PMID- 9041066
TI  - Integrating psychosocial services for lung volume reduction and lung
      transplantation patients into a pulmonary rehabilitation program.

PMID- 9041067
TI  - Exercise testing and training of patients with heart failure due to left
      ventricular systolic dysfunction.
AB  - Reducing the exercise intolerance and symptoms experienced by patients with
      chronic heart failure remains an important focus in their clinical care. A clear
      shortcoming exists; however, with respect to an appreciation that in addition to
      standard medical therapy, selected patients with stable heart failure also can
      benefit from a moderate exercise training program. Improvements in central
      transport, regional blood flow, and skeletal muscle histology and biochemistry
      all likely account for the increase in exercise capacity and delay in fatigue
      that these patients experience. Additionally, the autonomic imbalance that is
      characteristic of these patients is improved. Although the number of patients
      with heart failure participating in an exercise program is increasing, much work
      still exists relative to incorporating this treatment method into the care plans
      established by physicians and physician extenders.

PMID- 9041068
TI  - Quality of life and return to work 5 years after coronary artery bypass surgery.
      Long-term results of cardiac rehabilitation.
AB  - BACKGROUND: Rehabilitation is an important part of the treatment of patients with
      ischemic heart disease. Therefore, many patients undergoing coronary artery
      bypass surgery (CABS) also participate in cardiac rehabilitation programs. This
      study was conducted to investigate whether rehabilitation influences quality of
      life and work status after CABS. METHODS: Consecutive patients undergoing
      elective CABS were randomly assigned to a rehabilitation group (R, N = 119) and a
      hospital-treatment group (H N = 109). All patients received usual medical care.
      Group R participated in a rehabilitation program based on exercise and
      counseling. The follow-up time was 5 years. The measured domains of health
      related quality of life were heart symptoms, functional class, exercise capacity,
      use of medication, depression, the patients' perception of health, and overall
      life situation. The Nottingham Health Profile as a measure of perceived distress
      was used. RESULTS: Symptoms, use of medication, exercise capacity, and depression
      scores did not differ between groups R and H. Five years after the CABS, the
      patients in group R reported less restriction in physical mobility on the
      Nottingham Health Profile than patients in group H (P = 0.005), and more patients
      in group R than in group H perceived their health (P = 0.03) and overall life
      situation (P = 0.02) as good. The increase in the proportion of subjects working
      was higher in group R than group H at 3 years after the CABS (P = 0.02), but not
      at other follow-up times. CONCLUSION: A cardiac rehabilitation program in
      conjunction with usual medical care after CABS may induce a perception of
      improved health. The influence on return to work is limited.

PMID- 9041069
TI  - Reliability of perceived exertion during graded exercise testing in apparently
      healthy adults.
AB  - PURPOSE: Ratings of perceived exertion (RPE) are widely used for monitoring
      individuals during graded exercise testing. Studies of the reliability of RPEs
      across various exercise conditions have produced mixed results. The purpose of
      this study was to assess the reliability of RPEs during graded exercise testing
      by comparing the perceptual-physiological relationship between the Bruce and
      Balke treadmill protocols throughout a broad range of relative exercise
      intensities. METHODS: Thirty-eight middle-aged men and women completed two
      maximal treadmill graded exercise testing separated by 48 hours. Test order was
      randomly assigned. RPEs were compared across protocols and between gender at
      selected exercise intensities using a series of two-way analysis of variances
      with repeated measures. RESULTS: A comparison of RPEs (Borg 15-point scale)
      during the graded exercise testing revealed significant protocol and gender
      differences at 40%, 60% and 80% of maximal heart rate reserve. RPEs were
      significantly higher during the Balke protocol compared to the Bruce at each
      intensity (45% = 9.5 +/- 2.0 vs. 8.3 +/- 1.6; 60% = 12.7 +/- 2.4 vs. 11.1 +/-
      2.3; 80% = 15.7 +/- 2.2 vs. 14.1 +/- 2.0). In addition, men rated each intensity
      significantly higher than the women (P < 0.05). CONCLUSIONS: The results from the
      present study confirm that the perceptual-physiological relationship observed
      during graded exercise testing varies as a function of the treadmill protocol
      employed and that these differences extend throughout the exercise training
      intensity range (40--80% of maximal heart rate reserve) recommended for healthy
      adults. The perceptual differences between the protocols could not be accounted
      for by any of the physiological measures assessed within the study. These results
      have implications when using RPEs from exercise testing for exercise prescription
      purposes.

PMID- 9041070
TI  - Physical activity monitoring in patients with peripheral arterial occlusive
      disease.
AB  - PURPOSE: Physical activity is an important variable to measure in patients with
      peripheral arterial occlusive disease (PAOD) because of this relationship to
      cardiovascular disease morbidity and mortality. The purposes of this study were
      to (1) determine the reliability of measures of daily physical activity in PAOD
      participants using an accelerometer and a pedometer; and (2) assess the validity
      of both instruments by comparing them against validated physical activity
      questionnaires. METHODS: Forty-three patients with PAOD with a resting
      ankle/brachial index of 0.63 +/- 0.19 were monitored for 2 consecutive weekdays
      with an accelerometer and pedometer worn on each hip. The 48-hour monitoring
      period was repeated approximately 1 week later. RESULTS: The daily physical
      activity values obtained from the accelerometer were similar between the two
      testing periods, 352 +/- 248 kcal/day vs. 337 +/- 199 kcal/day; P = 0.61, with a
      reliability coefficient of r = 0.84. The steps obtained from the pedometer during
      each 2-day period also were similar, 4615 +/- 2839 steps/day vs. 4498 +/- 2768
      steps /day; P = 0.75, with a reliability coefficient of r = 0.86. The physical
      activity values from the accelerometer moderately correlated with the Minnesota
      Leisure Time Physical Activity Questionnaire, r = 0.33; P < 0.01, and the
      NASA/Johnson Space Center Physical Activity Scale, r = 0.44; P < 0.001.
      Similarly, the relationship between the steps obtained from the pedometer and
      physical Activity and the Minnesota Leisure Time Physical Activity and
      NASA/Johnson Space Center Physical Activity Scale questionnaires were
      significant, r = 0.46 and r = 0.51; P < 0.001, respectively. CONCLUSION: These
      findings indicate that an accelerometer and pedometer are two instruments that
      reliably estimate the physical activity levels of patients with PAOD over 2
      consecutive days. Furthermore, the activity questionnaires, suggesting that
      activity monitoring measures a different component of activities in patients with
      PAOD with intermittent claudication.

PMID- 9041071
TI  - A chance to make a difference.

PMID- 9041072
TI  - Evaluating videokeratoscopes.

PMID- 9041073
TI  - Vector analysis of residual cylinder.

PMID- 9041074
TI  - Preventing overcorrection and microperforations with RK.

PMID- 9041075
TI  - Monitoring a leaking bleb.

PMID- 9041076
TI  - Consultation section. Bilateral radial keratotomy (RK) for contact lens
      intolerance.

PMID- 9041077
TI  - Endoscope-assisted transscleral suture fixation of intraocular lenses.
AB  - We describe a new method for placing transscleral sutures when fixating posterior
      chamber intraocular lenses to the sulcus. An intraocular microendoscope with an
      18 gauge probe is used for direct sulcus observation and needle position
      assessment. The straight needle of a 10-0 polypropylene suture and the tip of the
      probe are placed in a 16 gauge silicone rubber tube to hold them together. Fixing
      the needle to the endoscope allows a direct view of its tip and requires only one
      hand. The other hand is used to grasp the tip of the needle when it comes out
      under the scleral flap after passing through the sulcus. Assessment of needle
      position with an endoscope avoids surgically induced iris root or ciliary body
      damage. Fixing the needle to the endoscope simplifies the surgical technique.

PMID- 9041078
TI  - Straight-entrance, sclerocorneal valve incision with horizontal sutures for
      poly(methyl methacrylate) intraocular lenses.
AB  - Self-sealing sclerocorneal tunnel incisions with an external frown entry are
      widely used for implantation of poly(methyl methacrylate) intraocular lenses.
      Although safe and effective, these incisions have certain drawbacks. We developed
      a wound construction in which a straight external incision is used in conjunction
      with a tension-free, infinity-type suture. Out of 100 consecutive cases, only two
      did not seal satisfactorily at the conclusion of surgery but were tight upon
      placement of re-enforcing sutures. Postoperatively, the valve remained tight in
      all cases; there were no cases of hypotony, filtering bleb, flat chamber, or
      pupil capture or endophthalmitis indicating transient leakage. Flattening in the
      vertical and steepening in the horizontal meridian were minor and nonprogressive.

PMID- 9041079
TI  - Topical interferon alpha 2b for corneal haze after excimer laser photorefractive
      keratectomy. The Melbourne Excimer Laser Group.
AB  - PURPOSE: To determine whether topical interferon alpha 2b (IFN-alpha) prevents
      corneal haze after excimer laser photorefractive keratectomy (PRK). SETTING:
      Tertiary referral ophthalmic hospital. METHOD: A prospective, double-blind,
      placebo-controlled, randomized study of 31 patients was undertaken. After surgery
      in a single institution, patients received a drop of either a placebo or IFN
      alpha (5 x 10(6) IU/ml) four times daily for 4 weeks. The main outcome measures
      were corneal haze, refraction, and visual acuity. RESULTS: The major side effect
      of interferon alpha treatment was a significant delay in epithelial healing by a
      mean of 2 days. The means of the average post-treatment clinical scores for haze
      in all patients up to 12 months after surgery were 0.46 +/- 0.25 for the IFN
      alpha group and 0.64 +/- 0.43 for the placebo group (P = .20). Of patients with a
      correction of greater than 5.00 diopters (D), the IFN-alpha group had
      significantly less haze over the course of the study (0.39 +/- 0.23 versus 0.98
      +/- 0.50; P = .03). After 12 months, the mean absolute spherical equivalent in
      the two groups was not significantly different (1.02 +/- 1.13 D versus 1.44 +/-
      2.64 D). There was a tendency toward better uncorrected visual acuity in the INF
      alpha group (P < .10, Kolmogorov-Smirnov). CONCLUSION: Topical IFN-alpha may
      merit further investigation as a treatment to reduce corneal haze after excimer
      laser PRK for corrections greater than 5.00 D.

PMID- 9041080
TI  - Photorefractive keratectomy for residual myopia after radial keratotomy.
AB  - PURPOSE: To evaluate the results of photorefractive keratectomy (PRK) to treat
      undercorrected radial keratotomy (RK). SETTING: Instituto de Oftalmologia Tadeu
      Cvintal, Sao Paulo, Brazil. METHODS: A consecutive series of 28 eyes that had PRK
      to treat residual myopia after RK were studied. Refractive visual and safety data
      were collected and evaluated. RESULTS: One year after PRK, 75% of eyes had an
      uncorrected visual acuity of 20/25 or better and 85%, 20/40 or better. All but
      one case maintained or improved best corrected visual acuity; one case decreased
      from 20/25 to 20/30. At 1 year, 75% of eyes were within 0.50 diopter (D) of
      emmetropia and 90% were within 1.00 D. Only one case was more than 1.00 D
      undercorrected (-1.125 D) at 1 year. Mean pre-RK myopia was -5.90 D (range -2.00
      to 11.80 D). Mean spherical equivalent improved from the residual postoperative
      level of -2.71 D +/- 0.86 (SD) before PRK to -0.21 +/- 0.86 D 1 to 3 months after
      PRK and to -0.40 +/- 0.43 D 1 year after PRK. CONCLUSION: Photorefractive
      keratectomy was efficacious in correcting residual myopia after RK in a group of
      selected patients.

PMID- 9041081
TI  - Effect of myopic excimer laser photorefractive keratectomy on the
      electrophysiologic function of the retina and optic nerve.
AB  - PURPOSE: To assess by electrophysiologic testing the effect of photorefractive
      keratectomy (PRK) on the retina and optic nerve. SETTING: Eye Clinic, S.
      Salvatore Hospital, L'Aquila University, Italy. METHODS: Standard pattern
      electroretinograms (P-ERGs) and standard pattern visual evoked potentials (P
      VEPs) were done in 25 eyes of 25 patients who had myopic PRK for an attempted
      correction between 5.00 and 15.00 diopters (D) (mean 8.00 D). Testing was done
      preoperatively and 3, 6, 12, and 18 months postoperatively. The contralateral
      eyes served as controls. During the follow-up, 3 patients (12%) developed steroid
      induced elevated intraocular pressure (IOP) that resolved after corticosteroid
      therapy was discontinued. RESULTS: No statistically significant differences were
      seen between treated and control eyes nor between treated eyes preoperatively and
      postoperatively. CONCLUSION: Myopic excimer laser PRK did not seem to affect the
      posterior segment. The transient steroid-induced IOP rise did not seem to cause
      functional impairment.

PMID- 9041082
TI  - Excimer laser photorefractive keratectomy for extreme myopia.
AB  - PURPOSE: To determine the efficacy, predictability, and safety of excimer laser
      photorefractive keratectomy (PRK) in treating very high myopia. SETTING: Laser
      Vision Harley Street, London, England. METHODS: Eighty-eight patients whose
      spherical errors ranged from -6.00 to -20.00 diopters (D) had PRK with the VISX
      20/20B excimer laser and a multizone ablation technique. The patients were
      divided into two groups of 44: those with errors up to -10.00 D and those with
      errors above -10.25 D. Visual acuity, manifest refraction, corneal haze, and
      topography were examined 1 week and 1, 2, 3, 6, and 12 months postoperatively.
      RESULTS: Minimum follow-up was 1 year. Predictability of results was greater in
      Group 1 than in Group 2 patients: 90.0% were within 1.00 D of intended correction
      and 70.0% were within 2.00 D, respectively. The average for both groups was 85.0%
      within 2.00 D and 63.6% within 1.00 D of intended correction. No serious
      complications or overcorrections were seen in either group. Preoperative
      astigmatism ranged from 1.50 to 5.50 D. Postoperatively, 82.0% of patients had no
      residual astigmatism; in the other 18.0%, it ranged from 0.50 to 2.50 D (83.0%
      had 1.00 D or less). Results with the multizone technique were more successful
      than those reported with the single- or dual-zone ablation techniques.
      CONCLUSIONS: High myopia was treated with reasonable success using the VISX
      20/20B excimer laser system and a multizone technique. Comparable studies using
      single- and dual-zone approaches appear to have less successful outcomes.

PMID- 9041083
TI  - Effect of incision direction on refractive outcome after radial keratotomy.
AB  - PURPOSE: To determine whether the direction of radial keratotomy (RK) incisions
      (centripetal versus centrifugal) affects refractive outcome. SETTING: Private
      ophthalmology office. METHODS: The database of a single surgeon was
      retrospectively reviewed. Stepwise regression was used to select significant
      predictors of refraction change in the population. In addition to incision
      direction, variables evaluated were optic zone diameter, number of incisions,
      patient age, corneal curvature, and planned incision depth. RESULTS: All
      variables except planned incision depth and corneal power affected refractive
      outcome. After controlling for number of incisions, optic zone diameter, and
      patient age, centripetal incisions decreased myopia 0.87 diopters more than
      centrifugal incisions. CONCLUSIONS: Our results, consistent with previous
      investigations, found that number of incisions, optic zone diameter, and patient
      age were significant predictors of refractive outcome after RK. Incision
      direction was also a significant predictor by itself or coupled with optic zone
      diameter and number of incisions, with the centripetal incision decreasing myopia
      more.

PMID- 9041084
TI  - Astigmatic change 1 year after excimer laser treatment of myopia and myopic
      astigmatism. Melbourne Excimer Laser Group.
AB  - PURPOSE: To evaluate the surgically induced astigmatism (SIA) 1 year after
      excimer laser photorefractive astigmatic keratectomy (PARK) and photorefractive
      keratectomy (PRK). SETTING: Royal Victorian Ear and Eye Hospital, Melbourne,
      Australia. METHODS: This study comprised 333 PARK patients and 155 PRK patients
      treated with a VISX 20/20 excimer laser and followed prospectively for 12 months.
      Vector analysis of the change in astigmatism was used to calculate the SIA in the
      PRK group and the percentage of astigmatism corrected in the PARK group. RESULTS:
      Among patients with low cylinders astigmatic correction varied greatly,
      particularly in those treated for large amounts of myopia. The spherical PRK
      treatments yielded a mean induced postoperative astigmatism of 0.47 diopter.
      There was a linear relationship between this inadvertent SIA and increasing
      myopia. CONCLUSION: Excimer laser surgery for myopia creates a low degree of
      random, unpredictable SIA that may be the result of irregular epithelial
      thickening during postoperative healing. This creates a background noise of
      astigmatic change upon which the targeted astigmatic correction is superimposed.

PMID- 9041085
TI  - Practice styles and preferences of ASCRS members--1995 survey.
AB  - A survey of the practice styles and preferences of the 1995 members of the
      American Society of Cataract and Refractive Surgery with a U.S. ZIP code was
      performed in September 1995. Approximately 27% (1500) of the 5500 questionnaires
      mailed were returned by the December cutoff date. Four main profile questions
      were used to cross-tabulate data: age of the ophthalmologist, geographic
      location, volume of cataract surgery per month, and volume of refractive surgery
      per month. Current data were compared with data in previous annual surveys.

PMID- 9041086
TI  - Cost effectiveness of a single-function treatment center for cataract surgery.
AB  - PURPOSE: To compare the clinical and cost effectiveness of two models for
      cataract treatment: a single-function Cataract Treatment Centre (CTC) and a
      general ophthalmology service. SETTING: Cataract Treatment Centre and the general
      ophthalmology service at Sunderland Eye Infirmary, Sunderland, United Kingdom.
      METHODS: Two hundred patients were studied using two models of care: 100 in the
      CTC and 100 in the general ophthalmology service. Outcome measures were best
      corrected visual at 3 months postoperatively or at discharge and occurrence of
      surgery-related complications. All direct costs to the National Health Service
      were identified, measure, and assessed. RESULTS: Clinical outcomes in the two
      groups were similar. The average cost per patient was 496.90 pounds ($760.25) at
      the CTC and 566.34 pounds ($866.50) at the general ophthalmology service. The
      cost per patient treated as a day case in the general service group was 495.84
      pounds ($758.63). Thus, treatment at the CTC was more cost effective than in the
      mixed service group and as cost effective as in the day case subgroup.
      CONCLUSIONS: Depending on local circumstances, day care must be delivered more
      cost effectively in a single-function center than in a general ophthalmology
      service. We recommend day care using local anesthesia and protocols for
      assessment, surgery, and follow-up.

PMID- 9041088
TI  - Secondary implantation of open-loop, flexible, anterior chamber intraocular
      lenses.
AB  - PURPOSE: To assess the results of implantation of secondary, open-loop, flexible,
      anterior chamber intraocular lenses (IOLs) and compare the findings with those of
      other published studies. SETTING: A combined ophthalmology and ear, nose, and
      throat hospital in Middlesbrough, Cleveland, England. METHODS: This retrospective
      study comprised 81 patients who had secondary implantation of a flexible, open
      loop, anterior chamber IOL by the one surgeon. The incidence of postoperative
      complications was ascertained, and best corrected preoperative and postoperative
      visual acuities were compared. RESULTS: Two serious complications occurred: one
      severe loss of vision that is still under investigation and one retinal
      detachment that was repaired with good residual visual function. Of all 81
      patients, 92.5% were within one Snellen line of their preoperative best corrected
      visual acuity. These results compare favorably with those of other published
      studies. CONCLUSION: Using an open-loop, flexible, anterior chamber lens for
      secondary implantation is still an acceptable way to treat aphakia. The poor
      reputation of these lenses is undeserved.

PMID- 9041087
TI  - Effect of capsulorhexis diameter on glare disability.
AB  - PURPOSE: To determine whether the diameter of the anterior capsulorhexis has an
      effect on postoperative glare. SETTING: Sapir Medical Center, Meir Hospital, Kfar
      Saba, Israel. METHODS: Forty patients had extracapsular cataract extraction
      (manual or phacoemulsification) through an intact continuous curvilinear
      capsulorhexis (CCC) of various sizes. The CCC diameter was measured and the
      opacity of the anterior and posterior capsules was evaluated before and after
      dilation of the pupils. Glare test (Miller-Nadler glare tester) was performed
      with the eyelid in a normal position and after lid elevation. RESULTS: The
      diameter of the CCC ranged from 3.50 to 7.00 mm (mean 4.87 mm). The anterior
      capsule was always opaque in the area of contact with the IOL material. None was
      graded clear; 60% were graded as +3. Mean glare disability prior to pupil
      dilation was 12.1 +/- 8.8 (SD) and after dilation, 17.3 +/- 9.7. There was no
      correlation between glare disability and the diameter of the capsulorhexis, the
      width of the exposed opacified capsular ring, or the grading of capsule
      opacification (anterior and posterior). Dilation of the pupil significantly
      increased glare disability (P = .016), unrelated to CCC diameter. CONCLUSION: A
      CCC larger than 3.5 mm does not induce significant glare.

PMID- 9041089
TI  - Comparison of viscoelastic substances used in phacoemulsification.
AB  - PURPOSE: To evaluate the usefulness of four viscoelastic agents during
      phacoemulsification: 2% hydroxypropylmethylcellulose (HPMC) (Methocel), 3% sodium
      hyaluronate with 4% chondroitin sulfate (Viscoat), 1% sodium hyaluronate
      (Healon), 1.4% sodium hyaluronate (Healon GV). SETTING: Eye Clinic,
      Kreiskrankenhaus Bad Hersfeld, Germany. METHODS: Two hundred patients, divided
      into four groups of 50 patients, received one of the viscoelastic substances
      during phacoemulsification and posterior chamber intraocular lens implantation.
      Patients were followed for 1 month. Visual acuity and intraocular pressure (IOP)
      were measured. The following were subjectively evaluated for each viscoelastic:
      corneal findings, anterior chamber reaction, visibility of intraocular structures
      and retention time during phacoemulsification, space maintaining ability, and
      removability and ease of injection. RESULTS: Postoperative IOP and visual acuity
      were comparable among the four groups. Viscoat tended to trap nuclear fragments
      and air bubbles during the phacoemulsification procedure, which decreased
      visibility during surgery. Space maintenance and injection ease were
      significantly better with Healon and Healon GV. CONCLUSION: The high molecular
      weight viscoelastics (Healon and Healon GV) performed better as viscosurgical
      tool during cataract surgery using phacoemulsification.

PMID- 9041090
TI  - Comparison of the effect of four viscoelastic agents on early postoperative
      intraocular pressure.
AB  - PURPOSE: To compare the effect of four commercially available viscoelastic agents
      on postoperative intraocular pressure (IOP). SETTING: Four outpatient sites.
      METHODS: Sixty-nine patients having routine extracapsular cataract extraction
      were enrolled in the study; 54 were available for a 3 month follow-up
      examination. The four viscoelastic agents were Amvisc, Amvisc Plus, Healon, and
      Viscoat. Intraocular pressure was measured preoperatively and at 2, 3, 4, 5, 6,
      8, 10, 12, and 24 hours and 3 months postoperatively. Pachymetry and endothelial
      cell counts were performed preoperatively and 3 months postoperatively. RESULTS:
      Mean postoperative IOP and IOP changes from baseline did not differ among the
      four treatment groups at any time. However, when mean maximal IOP was compared,
      the Healon group demonstrated the highest IOP increases (P = .0033). There was
      also a significant difference (P = .0015) among the treatment groups in the mean
      maximum postoperative change from baseline; the Healon group exhibited the
      largest mean change in IOP. At 3 months postoperatively, IOP values and
      pachymetry were normal for all treatment groups and were not statistically
      different among groups, indicating the four agents provided similar degree of
      endothelial protection and IOP stability. CONCLUSION: These results suggest that
      IOP increases occur in varying degrees and at varying times in the early
      postoperative period after cataract surgery using a viscoelastic agent.

PMID- 9041091
TI  - Effects of phacoemulsification time on the corneal endothelium using
      phacofracture and phaco chop techniques.
AB  - PURPOSE: To quantitatively assess early postoperative endothelial damage caused
      by two phacoemulsification techniques and to ascertain the effect of differences
      in phacoemulsification time. SETTING: Department of Ophthalmology, Umberto
      Hospital, Lugo, Italy. METHODS: This prospective study evaluated 100 patients who
      had phacoemulsification using one of two techniques: phaco chop (n = 50) or four
      quadrant, divide and conquer phacofracture (n = 50). The endothelium of both
      groups was analyzed preoperatively and 8 weeks postoperatively by specular
      microscopy. RESULTS: Phaco chop led to significantly shorter phacoemulsification
      time and less endothelial damage. Mean equivalent phacoemulsification time was
      25.53 seconds +/- 11.26 (SD) in the phaco chop group and 87.26 +/- 48.03 seconds
      in the phacofracture group. Endothelial cell loss was 4.72 +/- 1.2% and 13.80 +/-
      4.3%, respectively. CONCLUSION: The phaco chop technique led to shorter
      phacoemulsification time and less endothelial cell loss.

PMID- 9041092
TI  - Effect of applanation tonometry on mean corneal curvature.
AB  - PURPOSE: To evaluate whether applanation tonometry affects corneal curvature and
      if so, the implications for intraocular lens power calculation. SETTING:
      Birmingham and Midland Eye Hospital, Birmingham, England. METHODS: Twenty-two
      patients attending the preoperative assessment clinic were enrolled in the study.
      Keratometry was performed immediately before, 1 minute after, and 10 minutes
      after standard Goldmann tonometry. Main outcome measures were mean corneal
      refractive power and its reproducibility (coefficient of repeatability). RESULTS:
      No clinically significant difference was noted between preapplanation and
      postapplanation readings (P = .6), and reproducibility was not significantly
      affected. CONCLUSION: The results indicate that corneal applanation before
      keratometry does not compromise the prediction of postoperative refraction.

PMID- 9041093
TI  - Prevalence and surgical complications of pseudoexfoliation syndrome in Portuguese
      patients with senile cataract.
AB  - PURPOSE: To determine the prevalence and surgical complications of
      pseudoexfoliation syndrome (PES) in a Portuguese population of patients with
      senile cataract. SETTING: Department of Ophthalmology, Coimbra University
      Hospitals, Coimbra, Portugal. METHODS: In a prospective study, 183 consecutive
      patients with senile cataract referred to the Implant and Refractive Surgery
      Section of the Department of Ophthalmology were examined for PES. To determine
      the occurrence of intraoperative and postoperative complication of extracapsular
      extraction with posterior chamber intraocular lens implantation in patients with
      PES, two groups of similar age were compared: one with PES (n = 31) and a control
      group without PES (n = 31). RESULTS: The prevalence of PES in the 183 Portuguese
      patients with senile cataract was 23.5%. There was statistically significant
      difference between the two groups in the presence of phacodonesis (P < .05),
      insufficient intraoperative mydriasis (P < .001), need to perform
      sphincterotomies to facilitate nucleus expression (P < .01), and formation of
      pupillary fibrin membranes in the postoperative period (P < .01). These
      complication were more frequent in the PES group. Zonular breaks also occurred
      more often in patients with PES, although this was not statistically significant.
      CONCLUSIONS: Pseudoexfoliation syndrome was a common condition in patients with
      senile cataract having surgery in Portugal. Inadequate mydriasis was the major
      intraoperative difficulty; a pupil enlargement procedure should be performed in
      these cases. In the first days postoperatively, therapy with topical,
      subconjunctival, and systemic corticosteroids is recommended to reduce the
      inflammatory reaction in the anterior chamber.

PMID- 9041094
TI  - Multivariate analysis versus vector analysis to assess surgically induced
      astigmatism.
AB  - PURPOSE: To present a multivariate probability computation method for assessing
      surgically induced astigmatism. SETTING: Department of Ophthalmology, Rennes
      University Hospital, Rennes School of Medicine, France. METHODS: The multivariate
      method was used to evaluate 100 patients who had cataract surgery by
      phacoemulsification. Keratometry was recorded on the day before and 12 days after
      surgery. Surgically induced astigmatism was assessed by the multivariate method
      as well as by most of the published vector analysis methods. RESULTS: The mean
      surgical induced astigmatism (+/- SD) with the multivariate analysis was 1.18 +/-
      0.36 diopters (D) for the cylinder power and 25.00 +/- 5.50 degrees for the
      cylinder axis. With the vector analysis, the mean surgically induced astigmatism
      was 1.67 +/- 0.54 D with the Naylor, Jaffe, and Holladay methods; 0.45 +/- 0.30 D
      with the latest Naeser method; 1.34 +/- 0.38 D with the Cravy method (Cravy's
      vector); and -0.05 +/- 0.42 D for Cravy's delta K. CONCLUSION: Although vector
      methods constitute interesting geometrical models, their number and their lack of
      linearity and explicit expression of results make them unsuitable for statistical
      analysis. Instead, a reliable, easily programmable method that uses existing
      software is recommended.

PMID- 9041095
TI  - Accuracy in determining intraocular lens dioptric power assessed by
      interlaboratory tests.
AB  - PURPOSE: To describe a testing program conducted by a standards group as a guide
      for setting international tolerances for intraocular lens (IOL) dioptric power.
      SETTING: Multicenter study. METHODS: Seven biconvex, poly(methyl methacrylate)
      IOLs ranging in power from 10.00 through 30.00 diopter (D) were circulated among
      nine participating laboratories experienced in IOL optical measurements. Each
      laboratory performed repeated optical tests to determine dioptric power. These
      results were analyzed for repeatability and reproducibility in accordance with
      methods specified by the International Organization for Standardization. RESULTS:
      Intralaboratory repeatability was less than 0.5% of the dioptric power, and
      interlaboratory reproducibility, when following a normalized procedure for
      correction and conversion, was less than 1.0% of the dioptric power. CONCLUSION:
      Tolerance limits of +/0 0.30 D in the range 0 to 15.00 D, +/- 0.40 D for 15.50 to
      25.00 D, and +/- 0.50 D for 25.50 to 30.00 D have been proposed as an
      international standard for IOLs. The contribution of IOL power error within the
      limits of the standard are estimated to contribute less than 1.0% to the total
      error in postoperative refractive prediction.

PMID- 9041096
TI  - Lenticular astigmatism after penetrating eye injury.
AB  - Lenticular astigmatism of 5.00 diopters developed after penetrating injury in the
      eye of a 16-year-old boy. Full visual acuity, refraction, and crystalline lens
      clarity remained stable for more than 2 years. The high astigmatism, in
      conjunction with a spherical cornea and posterior lens capsule striae, indicates
      the lenticular origin of the astigmatism.

PMID- 9041097
TI  - Complications leading to surgery after breast implantation.
AB  - BACKGROUND: Local complications that require additional surgical procedures are
      an important problem for women with breast implants. METHODS: We studied 749
      women who lived in Olmsted County, Minnesota, and received a first breast implant
      at the Mayo Clinic between 1964 and 1991. We identified complications that
      occurred after the initial procedure and after any subsequent implantation. A
      complication was defined as a surgical procedure performed for any of the
      following reasons: capsular contracture; rupture of the implant; hematoma or
      bleeding; infection or seroma of the wound; chronic pain; extrusion, leakage, or
      sweating of the implant; necrosis of the nipple, areola, or flap; malfunction of
      the filler port of a tissue expander; and wound dehiscence. RESULTS: During
      follow-up (mean, 7.8 years; range, 0 to 25.8), 208 (27.8 percent) of the women
      underwent 450 additional implant-related surgical procedures. Ninety-one (20.2
      percent) were anticipated, staged procedures or were done because the patient
      requested a size change or aesthetic improvement, and 359 procedures (79.8
      percent) had at least one clinical indication (thus constituting a complication).
      Complications occurred in 178 (23.8 percent) of the 749 women and involved 274
      (18.8 percent) of the 1454 breasts with implants and 321 (18.8 percent) of the
      1703 implants. The most frequent problem was capsular contraction (272 cases),
      followed by rupture of the implant (60), hematoma (55), and wound infection (23).
      The rate of complications was significantly lower (P<0.001) among women with
      cosmetic implants (6.5 percent at one year, 12 percent at five years) than among
      women who underwent implantation after mastectomy for breast cancer (21.8 percent
      at one year, 34 percent at five years) or prophylactic mastectomy (17.3 percent
      at one year, 30.4 percent at five years). CONCLUSIONS: Women who have had breast
      implantation frequently experience local complications during the subsequent five
      years. Complications were significantly less frequent among patients who received
      implants for cosmetic reasons than among those who received implants after
      mastectomy for cancer or for cancer prophylaxis.

PMID- 9041098
TI  - Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women.
AB  - BACKGROUND: Plasma levels of plasminogen-activator inhibitor type 1 (PAI-1), an
      essential inhibitor of fibrinolysis in humans, increase in women after menopause,
      and this may contribute to the risk of cardiovascular disease. We studied the
      effects of hormone-replacement therapy on PAI-1 levels. METHODS: In a randomized,
      crossover study, we investigated the effects of oral conjugated estrogen (0.625
      mg per day) in 30 postmenopausal women and transdermal estradiol (0.1 mg per day)
      in 20 postmenopausal women, either alone or in combination with
      medroxyprogesterone acetate (2.5 mg daily) for one month, on plasma PAI-1 antigen
      levels. Degradation products of cross-linked fibrin (D-dimer) were measured in
      serum as an index of fibrinolysis. RESULTS: PAI-1 levels were inversely
      associated with D-dimer levels at base line (r= -0.540, P=0.002). Conjugated
      estrogen, both alone and in combination with medroxyprogesterone acetate, reduced
      mean (+/-SD) plasma levels of PAI-1 from 32+/-34 ng per milliliter to 14+/-10 ng
      per milliliter (P<0.001) and from 31+/-29 ng per milliliter to 15+/-11 ng per
      milliliter (P=0.003), respectively; there was a significant inverse correlation
      between pretreatment PAI-1 levels and the degree of reduction in these levels
      during therapy (r= -0.631, P<0.001 for conjugated estrogen; r = -0.507, P=0.004
      for combined therapy). The degree of reduction in PAI-1 levels was associated
      with increases in D-dimer levels both when conjugated estrogen was given alone
      (r= -0.572, P=0.001) and when combined hormone therapy was given (r= -0.541,
      P=0.002). Transdermal estradiol caused no significant changes in PAI-1 levels
      from base-line values. CONCLUSIONS: Conjugated estrogen, alone or combined with
      progestin therapy, reduced PAI-1 levels by approximately 50 percent in
      postmenopausal women and was associated with enhanced systemic fibrinolysis.
      These findings may partly explain the protective effect of hormone-replacement
      therapy with respect to coronary artery disease.

PMID- 9041099
TI  - Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis
      Ursodeoxycholic Acid Study Group.
AB  - BACKGROUND: There is no satisfactory medical therapy for patients with primary
      sclerosing cholangitis. Ursodiol (ursodeoxycholic acid) benefits patients with
      primary biliary cirrhosis, another cholestatic liver disease. METHODS: From May
      1989 to July 1995, we enrolled 105 patients with well-documented primary
      sclerosing cholangitis in a randomized, double-blind study comparing ursodiol (13
      to 15 mg per kilogram of body weight per day in divided doses) with placebo. The
      primary outcome was the time to treatment failure, defined as death; liver
      transplantation; histologic progression by two stages (of four) or progression to
      cirrhosis; the development of varices, ascites, or encephalopathy; sustained
      quadrupling of the serum bilirubin concentration; marked worsening of fatigue or
      pruritus; inability to tolerate the drug; or voluntary withdrawal from the study.
      RESULTS: We analyzed data on the 51 patients in each group with at least 3 months
      of follow-up; the median follow-up was 2.2 years. There was no significant
      difference between the groups in time to treatment failure (relative risk of
      treatment failure in the ursodiol group, 1.01; 95 percent confidence interval,
      0.6 to 1.7). During the first two years of follow-up, treatment was unsuccessful
      in 17 of 32 patients (53 percent) in the placebo group and 16 of 31 (52 percent)
      in the ursodiol group. There were also no differences in time to treatment
      failure for patients with early-stage disease or in time to liver
      transplantation. Ursodiol, but not placebo, was associated with improvement in
      serum alkaline phosphatase, aspartate aminotransferase, bilirubin, and albumin
      levels at one and two years. CONCLUSIONS: In a group of patients with well
      defined primary sclerosing cholangitis, ursodiol provided no clinical benefit.

PMID- 9041100
TI  - Sympathetic cardioneuropathy in dysautonomias.
AB  - BACKGROUND: The classification of dysautonomias has been confusing, and the
      pathophysiology obscure. We examined sympathetic innervation of the heart in
      patients with acquired, idiopathic dysautonomias using thoracic positron-emission
      tomography and assessments of the entry rate of the sympathetic neurotransmitter
      norepinephrine into the cardiac venous drainage (cardiac norepinephrine
      spillover). We related the laboratory findings to signs of sympathetic
      neurocirculatory failure (orthostatic hypotension and abnormal blood-pressure
      responses associated with the Valsalva maneuver), central neural degeneration,
      and responsiveness to treatment with levodopa-carbidopa (Sinemet). METHODS:
      Cardiac scans were obtained after intravenous administration of 6
      [18F]fluorodopamine in 26 patients with dysautonomia. Fourteen had sympathetic
      neurocirculatory failure--three with no signs of central neurodegeneration (pure
      autonomic failure), two with parkinsonism responsive to treatment with levodopa
      carbidopa, and nine with central neurodegeneration unresponsive to treatment with
      levodopa-carbidopa (the Shy-Drager syndrome). The rates of cardiac norepinephrine
      spillover were estimated on the basis of concentrations of intravenously infused
      [3H]norepinephrine during catheterization of the right side of the heart.
      RESULTS: Patients with pure autonomic failure or parkinsonism and sympathetic
      neurocirculatory failure had no myocardial 6-[18F]fluorodopamine-derived
      radioactivity or cardiac norepinephrine spillover, indicating loss of myocardial
      sympathetic-nerve terminals, whereas patients with the Shy-Drager syndrome had
      increased levels of 6-[18F]fluorodopamine-derived radioactivity, indicating
      intact sympathetic terminals and absent nerve traffic. Patients with dysautonomia
      who did not have sympathetic neurocirculatory failure had normal levels of 6
      [18F]fluorodopamine-derived radioactivity in myocardium and normal rates of
      cardiac norepinephrine spillover. CONCLUSIONS: The results of 6
      [18F]fluorodopamine positron-emission tomography and neurochemical analyses
      support a new clinical pathophysiologic classification of dysautonomias, based on
      the occurrence of sympathetic neurocirculatory failure, signs of central
      neurodegeneration, and responsiveness to levodopa-carbidopa.

PMID- 9041101
TI  - Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the
      sulfonylurea receptor.

PMID- 9041102
TI  - Images in clinical medicine. Meningococcemia.

PMID- 9041103
TI  - Treatment of bacterial meningitis.

PMID- 9041104
TI  - Breast implantation--the quest for safety and quality.

PMID- 9041105
TI  - Toward better treatment of primary sclerosing cholangitis.

PMID- 9041106
TI  - Autonomic disorders and their recognition.

PMID- 9041107
TI  - Subpoenas and science--when lawyers force their way into the laboratory.

PMID- 9041108
TI  - A 3-D model for chromatin organisation of G1 and G2 populations from quantitative
      confocal image analysis.
AB  - A study on the chromatin organisation of synchronised G1 and G2 populations of
      maize root cell nuclei is reported using 3-D images acquired with a confocal
      fluorescence microscope. The analysis is based on the concept of accessibility.
      Accessibility of a position x is the effort to arrive at x, when choosing the
      minimum effort path to arrive at x from the nuclear border. The effort is then
      taken to be proportional to the amount of all mass encountered on the path, and
      computed by a technique called the grey valued distance transform. The approach
      relies heavily on quantitative analysis of the intensity information. Hence,
      considerable attention was paid to the quantitative modification of the confocal
      intensity values by diffraction, absorption and scatter corrections. Three
      texture features are extracted from the accessibility maps: the global object
      inaccessibility, the relative object accessibility, and the object homogeneity.
      On the basis of individual texture features, no distinction between the G1 and G2
      populations could be established. However, the three features combined did show a
      clear difference with a high significance.

PMID- 9041109
TI  - Influence of fluorochrome labeling density on the photobleaching kinetics of
      fluorescein in microscopy.
AB  - The objective of this study was to identify, through kinetic analysis of
      individual elementary reactions, the conditions under which a simple first-order
      photobleaching kinetic model is sufficient for quantitative fluorescence
      measurements, and those under which more complex photobleaching kinetics must be
      considered. Three model systems of various fluorophore densities and
      distributions were employed to verify the kinetic analysis. The results showed
      that the photobleaching kinetics of free fluorescein at concentrations lower than
      5 microM corresponded closely to a single exponential function and therefore
      involved predominantly simple unimolecular or pseudounimolecular photochemical
      reactions. When fluorescein was bound to polyvinyl alcohol (PVA) molecules, the
      photobleaching kinetics of the densely labeled PVA deviated more from a single
      exponential function than sparsely labeled PVA. When fluorescein was bound to a
      DNA probe, the photobleaching kinetics were more complex and deviated
      significantly from a single-exponential function, due to one or more bimolecular
      processes with apparent concentration-dependent photobleaching rate constants.
      The practical applications of time-integrated fluorescence emission are discussed
      in the context of simple and complex photobleaching kinetics.

PMID- 9041110
TI  - Quantitative flow cytometric detection of specific microorganisms in soil samples
      using rRNA targeted fluorescent probes and ethidium bromide.
AB  - Specific detection and accurate enumeration of microorganisms in the environment
      have been hampered by the lack of suitable techniques. A three-parameter flow
      cytometric method (FCM) was developed to detect quantitatively Sphingomonas sp.
      strain 107 inoculated into soil samples. By combining light scattering profiles
      (i.e., morphological properties), ethidium bromide (EtBr) influx (i.e., wall
      permeability), and fluorescence in situ hybridization against the 16S rRNA (i.e.,
      detection specificity), we could accurately discriminate the bacterium of
      interest from the indigenous microflora and soil debris. EtBr was used, first, to
      determine the optimal cell wall permeabilization treatment to allow
      oligonucleotide probes to enter the bacterial cells and, second, to achieve clear
      discrimination of fixed cells from debris in soil samples. This method allowed
      effective qualitative and quantitative analysis by fluorescence in situ
      hybridization. The results showed that the detection threshold by FCM was 3 x
      10(4) cells/g of dry soil. Cell counts deduced from FCM analysis were similar to
      those obtained by the colony forming unit assay when soils contained fewer than 3
      x 106 cells/g dry soil. This method should be useful for either quantitative
      monitoring of microorganisms inoculated in contaminated soil samples during
      bioremediation or detecting known bacterial strains in environmental samples.

PMID- 9041111
TI  - Theoretical basis for sampling statistics useful for detecting and isolating rare
      cells using flow cytometry and cell sorting.
AB  - This paper describes new approaches to calculating the number of cells that need
      to be processed using flow cytometry (FCM) techniques and the subsequent time
      required in order to isolate a specific number of cells having selected
      characteristics. The methods proposed use probabilistic assumptions about the
      contents of the sample to be sorted, logarithmic/exponential transformations to
      avert the computer "underflow" and "overflow" limitations of brute force
      calculations for the parameters of the binomial distribution imposed by existing
      computer hardware, and an established mathematical procedure for calculating
      error bounds for the normal approximation to the binomial distribution. Estimates
      are derived for the total number of cells in the FCM sample volume that must be
      available for processing and, for given FCM cell sorting decision speeds, the
      total elapsed times necessary to conduct particular experiments. The proposed
      approach obviates the need to resort to calculation expediencies such as the
      theoretically limited Poisson approximation for what can be considered a
      Bernoulli process mathematically characterized by the binomial distribution.
      Tables and graphs illustrate the projected times required to complete FCM
      experiments as a function of "effective" cell sorting decision speeds. Results
      from this paper also demonstrate that, as the "effective" cell sorting decision
      speed increases, there may not be a corresponding linear decrease in the time
      required to sort a given number of cells with selected statistical properties.
      The focus of this paper is on the use of innovative mathematical techniques for
      the design of experiments involving rare cell sorting. However, these same
      computational approaches may also prove useful for the high-speed enrichment
      sorting of non-rare cell subpopulations.

PMID- 9041112
TI  - A transition probability cell cycle model simulation of bivariate
      DNA/bromodeoxyuridine distributions.
AB  - The transition probability cell cycle model is extended to describe both cell
      cycle variability and incorporation of bromodeoxyuridine (BrdUrd). The model can
      simulate BrdUrd uptake in both pulse-chase and continuous-labeling experiments.
      With the use of a random transition, variability due to cell cycle progression is
      distinguished from dispersion due to staining and machine errors in the
      generation of bivariate DNA/BrdUrd distributions. In a comparative test with a
      compartmental model developed by Yanagisawa et al. (Cytometry 6:550-562, 1985),
      the present model is shown to provide realistic simulations with fewer model
      parameters and with the ability to describe gradual asynchronization of cell
      cycle cohorts. With model predictions as the basis, a simulated experiment is
      performed to illustrate the difficulty in analyzing bivariate distributions. The
      simulated experiment illustrated that it is very easy to overestimate unlabeled
      cell fractions, and, as a result, matching the periodicity of the cell cycle
      cohort movements is more reliable in the estimation of model parameters.

PMID- 9041113
TI  - Separation of cells at different times within G2 and mitosis by cyclin B1 flow
      cytometry.
AB  - Multivariate flow cytometry using specific cyclin proteins and DNA content can
      identify cell populations at different points within the cell cycle.
      Quantification of cyclin B1 and DNA content reveals that cells with high levels
      of cyclin B1 predominantly have a 4C DNA content and are therefore in G2 or
      mitosis. We have examined whether separation of cells by levels of cyclin B1
      could be used to discriminate cells at discrete times within these phases. Post
      replicative cells progressively enter into fractions with higher levels of cyclin
      B1, indicating that this protein can be used as a marker of time in G2.
      Furthermore, cells in particular phases of mitosis can be greatly enriched by
      separation based on cyclin B1 levels. This method can thus be used to isolate
      cells at specific times within G2 and mitosis, periods of the cell cycle that
      have been difficult to study by cell fractionation.

PMID- 9041114
TI  - Flow cytometric analysis of in vivo polyamine deprivation in Lewis lung carcinoma
      (3LL) cells using the monoclonal antibody SPM8-2.
AB  - It has previously been shown that the monoclonal antibody SPM8-2 recognizes free
      spermine and spermidine as well as polyamines bound by an amide bond. In the
      present work it is demonstrated that this antibody also interacts with
      spermidine, spermine, and to a lesser extent N1- and N8-acetyl spermidine in an
      ELISA test where the polyamines are bound by reaction with formaldehyde. 3LL
      Lewis lung carcinoma cells from tumor-grafted mice were labeled with fluorescein
      conjugated monoclonal antibody SPM8-2 and analyzed by flow cytometry. Both viable
      cells and formaldehyde-fixed and subsequently permeabilized cells showed
      fluorescent staining. However, most polyamines present in the cells are not
      directly available for antibody binding. Treatment of fixed cells with DNase or
      RNase greatly increased fluorescent staining, suggesting that some polyamines are
      co-localized with DNA and RNA. Antibody labeling of the cells was prevented by
      addition of free spermine. 3LL cells from tumors of mice treated by a polyamine
      depleting regimen had decreased intracellular spermidine levels and bound less
      antibody when compared to untreated controls. After digestion with RNase, the
      cells from treated mice bound considerably less fluorescent antibody than tumor
      cells from untreated mice, while their RNA content was similar. In contrast,
      fluorescent staining after DNase digestion was only slightly affected by the
      treatment with a polyamine depleting regimen. This suggests that the pools of
      polyamines which are co-localized with RNA are depleted more readily than those
      associated with DNA. Since only a small proportion of the intracellular
      polyamines is accessible to the bulky antibodies, treatment with hydrolytic
      enzymes (DNase, RNase) is necessary to reveal specific compartments of the
      polyamines and to demonstrate qualitative and semi-quantitative differences of
      their distribution within cells.

PMID- 9041116
TI  - Flow cytometric determination of endocytosis of viable labelled Legionella
      pneumophila by Acanthamoeba palestinensis.
AB  - Endocytosis of fluorescently labelled cells of Legionella pneumophila (L.
      pneumophila) by free-living Acanthamoeba palestinensis (A. palestinensis) has
      been studied using flow cytometry. L. pneumophila cells were labelled with CM
      DiI, a lipophilic fluorescent probe under conditions that did not modify
      viability. Coculturing the bacteria with amoebae was accompanied by rapid
      endocytosis; after 5 min, 90% of the amoebae had internalized bacteria. This
      percentage remained unchanged during further coculture, but the number of
      bacteria ingested per amoeba increased. Moreover, the number of ingested bacteria
      was found to be dependent on the size of the amoeba. The validity of the
      internalization analyzed by flow cytometry was confirmed by observation using
      epifluorescence and phase contrast microscopy. CM-DiI labelling associated with
      flow cytometry provides a very valuable technique for the determination of
      bacteria endocytosis by free-living amoeba.

PMID- 9041115
TI  - Flow cytometric analysis of glucose transport by rat brain cells.
AB  - The fluorescent, non-metabolizable glucose analog 6-[N-(7-nitrobenz-2-oxa-1,3
      diazol-4-yl)amino]-6-deoxyglucose (NBDG) was used to measure rates of hexose
      transport by dissociated brain cells from developing and adult rats. Flow
      cytometric analysis of glucose uptake and expression of glucose transporters was
      performed by mapping on size by granularity, which discriminated between neurons
      and astrocytes in a suspension of mixed brain cells. These mapped cell
      populations were identified by immunofluorescent staining with antisera to neuron
      specific enolase (NSE) and glial fibrillary acidic protein (GFAP). Specific
      uptake of the analog by membrane glucose transporters was confirmed by its
      inhibition by D-glucose and by cytochalasin B. Both neurons and astrocytes
      expressed the GLUT1 and GLUT3 transporter isoforms. This was confirmed by the
      additive inhibition of NBDG uptake by antibodies to these transporter isoforms in
      both cell types. The advantages of flow cytometric analysis of glucose transport
      include continuous monitoring over extremely short periods of time, increased
      precision of cell-by-cell flow cytometric measurements versus average uptake
      rates obtained with radioisotopes, and simultaneous analysis of uptake by
      different cell populations. Moreover, both uptake rates and the abundance of
      specific transporters can be determined directly and rapidly on the same cell
      suspension.

PMID- 9041117
TI  - Bax upregulation is an early event in cisplatin-induced apoptosis in human
      testicular germ-cell tumor cell line NT2, as quantitated by flow cytometry.
AB  - Expression of the apoptosis-associated proteins Bcl-2 and Bax was quantitated by
      flow cytometry (FCM) in chemosensitive testicular germ-cell tumor NT2 cells, and
      the results were compared with those obtained by Western blotting. NT2 cells were
      incubated with cisplatin (3.1 microM for 2 h at 37 degrees C), and 24, 48, and 72
      h later were analyzed for induction of apoptosis, and for modulation of the
      expression of cell death suppressing protein Bcl-2, as well as cell death
      promoting protein Bax. Apoptosis was quantitated by binding of annexin V
      conjugated with fluorescein isothiocyanate (FITC) to the cell membrane. Cisplatin
      treatment induced apoptosis in NT2 cells. The apoptotic cell population increased
      in time, and at t = 72 h after drug incubation, about 90% of cells that were
      present in the cell culture were apoptotic. Subsequently, we determined the
      expression of the Bcl-2 and Bax proteins by FCM and Western blotting before and
      after drug treatment. NT2 cells had low constitutive expression levels of Bcl-2
      and elevated constitutive expression levels of Bax protein, as determined by both
      methods. At t = 24 h and 48 h after drug treatment, no changes were observed in
      the expression of the Bcl-2 protein, as quantitated by FCM and Western blotting.
      Also, the expression of the Bax protein had not changed, based on Western
      blotting. However, FCM revealed that in a specific subpopulation of drug-treated
      NT2 cells, Bax expression was increased. On the basis of forward and
      perpendicular light-scatter this subpopulation, which consisted of large, early
      apoptotic, swollen cells with increased internal complexity, was sorted, and
      showed abundant Bax protein by FCM and Western blotting. Our results demonstrate
      that the chemosensitivity of NT2 cells is probably due to a low intrinsic
      threshold for drug-induced apoptosis that is accompanied by overexpression of the
      death-promoting Bax protein during the early stages of the apoptotic process. We
      conclude that FCM is superior to Western blotting for the detection of
      heterogeneous expression of Bax in a given cell population.

PMID- 9041118
TI  - Multi-parameter flow cytometric analysis with detection of the Ki67-Ag in
      paraffin embedded mammary carcinomas.
AB  - In the present study we describe a novel multiparameter flow cytometric (FCM)
      assay to estimate the fraction of cycling cells in epithelial tumors derived from
      fresh frozen as well as archival material. To this end, MCF-7 cells as well as a
      series of breast carcinomas (n = 10; fresh frozen as well as formalin fixed and
      paraffin embedded) were stained using a panel of different antibodies directed
      against the Ki67-Ag (DAKO/PC, MIB-1, Ki-S5, and poly-Ki67) for a 3-parameter
      cytokeratin/Ki67-Ag/DNA FCM analysis. Whereas all Ki67-Ag antibodies work equally
      well in the methanol fixed cell line, MIB-1 and Ki-S5 epitopes are retained in
      cell suspensions mechanically derived from fresh frozen tissue. Only antibody Ki
      S5 shows specific nucleolar staining patterns in cell suspensions prepared by
      trypsin digestion of formalin fixed, paraffin embedded tissue sections. A good
      correlation was found between the fractions of Ki67-Ag-positive epithelial cells
      measured in cell suspensions derived from fresh frozen and the corresponding
      formalin fixed and paraffin embedded tumor samples. Furthermore, the fraction of
      Ki67-Ag-positive epithelial cells as determined by 3-parameter FCM correlated
      very well with the Ki67-Ag-labeling index in paraffin embedded tissue sections.

PMID- 9041119
TI  - Sample preparation from paraffin-embedded tissue specimens for laser scanning
      cytometric DNA analysis.
AB  - We have developed a simple, rapid method for isolating cells from a block of
      formalin-fixed, paraffin-embedded tissue specimen for laser scanning cytometric
      (LSC) DNA analysis by using a grater. The scraping-like tissue samples were
      obtained by grating a paraffin-embedded tissue block. The grated samples were
      collected, put into a small plastic tube, and deparaffinized with xylene.
      Subsequently, the samples were immersed in 100% ethanol to remove the xylene.
      After using a syringe with a 26-gauge needle and filtering through 40-microm
      nylon mesh, the cells suspended in ethanol were dropped directly onto a glass
      slide. As a result, isolated cells adhered tightly to the glass slide. The slides
      mounted with isolated cells were treated with 0.1% pepsin in 0.1 N HCl for 1 h at
      37 degrees C and then 0.1% RNase for 10 min at room temperature. The slides were
      dipped in propidium iodide (25 microg/ml) to stain DNA and sealed with nail
      varnish. The coefficients of variation for histograms were small enough to detect
      an aneuploid peak close to the diploid peak.

PMID- 9041120
TI  - Developmental regulation of the vertebrate globin multigene family.
AB  - "Hemoglobin switching," or the sequential expression of globin genes in erythroid
      cells during development, has provided an important paradigm for tissue- and
      stage-specific gene regulation. Over the past decade, regulatory DNA sequences
      and transcription factors involved in controlling the expression of individual
      globin genes in erythroid cells have been identified. The picture that has
      emerged indicates that gene proximal control elements collaborate with a "locus
      control region" located far upstream - probably via a DNA looping mechanism - to
      ensure that each gene is turned on only in erythroid cells and at the appropriate
      time during development. Interactions among the various regulatory sequences are
      thought to be mediated and stabilized by an array of tissue-specific and
      ubiquitous proteins. Chromatin structure plays a critical but still poorly
      understood role in this process.

PMID- 9041121
TI  - Characterization of mouse fibronectin alternative mRNAs reveals an unusual
      isoform present transiently during liver development.
AB  - Fibronectins are found in many extracellular matrices as well as being abundant
      plasma proteins. The plasma isoforms of fibronectin, which are synthesized in the
      adult by liver hepatocytes, differ from those derived from most other cells and
      tissues due to alternative mRNA splicing. Studies in several vertebrates have
      indicated that FN alternative splicing is regulated spatially and temporally
      during development. The mouse represents an attractive organism in which to study
      the regulation of fibronectin splicing during development, but the patterns of
      fibronectin alternative splicing were not known for this species. Mouse
      fibronectin cDNA clones were isolated and sequenced, revealing > 95% identity
      with rat fibronectin at the amino acid level; all three segments that undergo
      alternative splicing are well conserved. RNase protection and RT-PCR were used to
      determine the patterns of alternative splicing that occur in fibroblasts and
      adult liver, sources of cellular and plasma fibronectins. Only A-B-mRNAs were
      detected in liver, and three V region variants were observed, corresponding to
      the protein isoforms V120, V95, and V0. Fibroblasts produced mRNAs that were
      heterogeneous for A and B splicing, but all RNAs contained V120. These patterns
      contrast with the embryonic form (B+A+V120). Characterization of fibronectin
      mRNAs from livers of fetal and newborn mice revealed that a significant level of
      B+ mRNA was present throughout late gestation, declining at birth. Little A+ mRNA
      was present, and the adult liver V region pattern was observed at all stages.
      Thus, fibronectin splicing changes during liver development are noncoordinate.
      One consequence of this temporal regulation is the transient synthesis of B+
      mRNAs, including a novel isoform, B+A-V0.

PMID- 9041122
TI  - Specific binding sites for a pol III transcriptional repressor and pol II
      transcription factor YY1 within the internucleosomal spacer region in primate Alu
      repetitive elements.
AB  - Alu interspersed repetitive elements possess internal RNA polymerase III
      promoters that are transcribed in vitro and in transfected mouse cells but are
      nearly silent in human HeLa cells. Transcriptional repression of these elements
      is to some extent reversible, as pol III-dependent Alu expression can be induced
      with herpes simplex or adenovirus. To assess whether sequence-specific DNA
      binding proteins might contribute to Alu transcriptional silencing, we examined
      the internucleosomal spacer region surrounding the B box of the Alu pol III
      promoter in HeLa cell nuclei for evidence of proteins bound at specific sites in
      vivo. We identified a DNase I-hypersensitive site 5' to the B box and a DNase I
      resistant region 3' to the B box in nuclei. An Alu-specific repressor binds to a
      5-bp inverted repeat motif overlapping the 5' end of the TFIIIC binding site and
      may inhibit pol III transcription through competitive displacement. The level of
      Alu-specific pol III repressor activity is significantly reduced in adenovirus
      infected HeLa cells, suggesting that the repressor may contribute to Alu
      transcriptional silencing in vivo. The 3' DNase I-resistant region coincided with
      a binding site for the pol II transcription factor YY1 in vitro. YY1 is one of
      the major proteins in HeLa cells having binding specificity for Alu elements. YY1
      bound to tandem arrays of genomic Alu elements may play a role in chromatin
      organization and silencing.

PMID- 9041123
TI  - Cross-talk between thyroid hormone and specific retinoid X receptor subtypes in
      yeast selectively regulates cognate ligand actions.
AB  - Thyroid (T3) hormone beta1 (TR) and 9-cis retinoic acid (9c-RA) retinoid X
      receptors (RXR) can form heterodimer complexes that bind to hormone response
      elements (HREs) in target genes to either activate or repress transcription.
      However, the action of each cognate ligand and the accessory cellular factors
      that can differentially regulate the transcriptional responses of a heterodimer
      DNA complex are not well understood. Studies in most mammalian cell lines have
      demonstrated that 9c-RA cannot bind or transactivate TR/RXR-T3 response element
      (TRE) complexes. In contrast, when identical heterodimer complexes were
      coexpressed in the yeast (Saccharomyces cerevisiae) with single copy typical TREs
      [i.e., DR+4 (direct repeat), F2 (everted repeat), or PAL (inverted repeat) DNA
      response elements] we observed that i) unliganded TRbeta1 homodimers had
      constitutive action on F2 and PAL but not DR4 TREs; ii) TRbeta1 homodimer
      responsivity to T3 ligand was relatively weak (less than twofold) and was only
      demonstrable on F2 but not PAL or DR4-TREs, whereas TRbeta1 heterodimers
      responded to T3 when RXRgamma but not RXR alpha was the heterodimeric partner;
      iii) RXR responsivity to 9c-RA (three- to sixfold) could be demonstrated only on
      palindromic TREs that could be enhanced by TRbeta1 on all TREs; iv) T3 + 9c-RA
      ligands increased (additively or synergistically) transactivation when RXRgamma
      but not alpha heterodimerized with TRbeta1 on both typical as well as atypical
      (DR1, DR3, DR5, and F2M) TREs. Substitutions for wild-type TRbeta1 of C-terminus
      mutants deficient in dimerization with RXRs abrogated the anticipated single and
      dual cognate ligand-induced effects on TRbeta1/RXRgamma transactivation of DR4
      TREs, whereas mutants with preserved dimerization function but impaired T3
      transactivation regions could maintain an enhanced 9c-RA response but were devoid
      of the anticipated T3 and dual (T3 + 9c-RA) cognate ligand-induced effects. Thus,
      the ligand-inducible response of TR and RXR homodimers expressed in yeast are
      relatively weak but can be further enhanced by TRbeta1 cross-talk with specific
      RXR subtypes in the presence of both cognate ligands.

PMID- 9041124
TI  - Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a
      coactivator of peroxisome proliferator-activated receptor gamma.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the
      nuclear receptor superfamily, is expressed predominantly in adipose tissue.
      Forced expression of the two isoforms of this receptor, PPARgamma1 and
      PPARgamma2, in fibroblasts initiates a transcriptional cascade that leads to the
      development of adipocyte phenotype. Using the yeast two-hybrid system and GAL4
      PPARgamma as bait to screen mouse liver cDNA library, we isolated a mouse steroid
      receptor coactivator (mSRC-1) involved in nuclear hormone receptor
      transcriptional activity as a mPPARgamma interactive protein. mSRC-1 cDNA we
      isolated contains an open reading frame of 1447 amino acids and encodes a new
      member of the basic helix-loop-helix-PAS domain family. We show that the binding
      of mSRC-1 to mPPARgamma is ligand independent and coexpression of mSRC-1 with
      mPPARgamma increases the transcriptional activity of mPPARgamma in the presence
      of mPPARgamma ligand. We have identified the presence of two putative mPPARgamma
      binding sites in the mSRC-1, one between residues 620 and 789, and the second
      between residues 1231 and 1447. These two regions exhibit different degrees of
      binding affinity for mPPARgamma. We also show that mSRC-1 exhibits its own
      constitutive transcriptional activity in the yeast as well as in mammalian cells.
      These results suggest that mSRC-1 interacts with PPARgamma and plays a role in
      the PPARgamma-mediated signaling pathway.

PMID- 9041125
TI  - beta-Hexosaminidase immunolocalization and alpha- and beta-subunit gene
      expression in the rat testis and epididymis.
AB  - beta-hexosaminidase is an essential lysosomal enzyme whose absence in man results
      in a group of disorders, the G(M2) gangliosidoses. beta-hexosaminidase activity
      is many times higher in the epididymis than in other tissues, is present in
      sperm, and is postulated to be required for mammalian fertilization. To better
      understand which cells are responsible for beta-hexosaminidase expression and how
      it is regulated in the male reproductive system, we quantitated the mRNA
      expression of the alpha- and beta-subunits of beta-hexosaminidase and carried out
      immunocytochemical localization studies of the enzyme in the rat testis and
      epididymis. beta-hexosaminidase alpha-subunit mRNA was abundant and
      differentially expressed in the adult rat testis and epididymis, at 13- and 2
      fold brain levels, respectively. In contrast, beta-subunit mRNA levels in the
      testis and epididymis were 0.3- and 5-fold brain levels. During testis
      development from 7-91 postnatal days of age, testis levels of alpha-subunit mRNA
      increased 10-fold and coincided with the appearance of spermatocytes and
      spermatids in the epithelium; in contrast, beta-subunit mRNA was expressed at low
      levels throughout tests development. In isolated male germ cells, beta
      hexosaminidase alpha-subunit expression was most abundant in haploid round
      spermatids, whereas the beta-subunit mRNA was not detected in germ cells. Within
      the epididymis both alpha- and beta-subunit mRNA concentrations were highest in
      the corpus, with 1.5-fold and 9-fold initial segment values, respectively. Light
      microscopic immunocytochemistry revealed that beta-hexosaminidase was localized
      to Sertoli cells and interstitial macrophages in the testis. In the epididymis,
      beta-hexosaminidase staining was most intense in narrow cells in the initial
      segment, principal cells in the caput and proximal corpus, and clear cells
      throughout the duct. Electron microscopic immunocytochemistry revealed that beta
      hexosaminidase was predominantly present in lysosomes in Sertoli and epididymal
      cells. The cellular and regional specificity of beta-hexosaminidase
      immunolocalization suggest an important role for the enzyme in testicular and
      epididymal functions.

PMID- 9041126
TI  - Primary structures of sperm-specific basic nuclear proteins and gene expression
      in Japanese newt, Cynops pyrrhogaster.
AB  - Electrophoretic analyses of acid extracts from mature sperm of newt, Cynops
      pyrrhogaster, on acid/urea/Triton X-100 polyacrylamide gel showed the exclusive
      occurrence of sperm-specific nuclear basic proteins (SBPs), which moved faster
      than somatic histones on the gel. These SBPs were eluted separately by reversed
      phase-high-performance liquid chromatography as two large peaks and a few small
      peaks. Of these, only the small peaks disappeared with treatment of the acid
      extracts with alkaline phosphatase before they were injected into the column, so
      that there were only two distinct components: NP1 and NP2. Determination of amino
      acid sequences by the Edman method as well as by sequencing of cDNA for both
      components indicated that each protein consisted of 43 (NP1) or 48 (NP2) amino
      acid residues, rich in arginine residues (53.5% in NP1; 47.9% in NP2), forming
      the clusters. They had molecular masses of 5,386 Da (NP1) and 5,748 Da (NP2),
      respectively. Northern blot analysis using cDNAs as probes indicated that mRNAs
      for both NP1 and NP2 occurred not in primary spermatocytes but in round
      spermatids. In situ hybridization analyses using antisense RNA for NP1 as a probe
      clearly showed the first appearance of NP1 mRNA at the late stage of round
      spermatid.

PMID- 9041127
TI  - The murine Spam1 gene: RNA expression pattern and lower steady-state levels
      associated with the Rb(6.16) translocation.
AB  - Recently we mapped the murine Spam1 gene to the proximal region of chromosome 6
      (MMU 6). Based on the map location and physiological characteristics of its
      encoded sperm antigen, the gene is an attractive candidate for the sperm
      dysfunction seen in Rb(6.16) translocation heterozygotes and the reduced
      fertility of homozygotes. We have analyzed the expression of Spam1 mRNA in normal
      and Rb(6.16) mice. The expression of Spam1 mRNA was found to be: 1) tissue
      specific; it is expressed exclusively in testis; and 2) developmentally
      regulated, with a haploid expression. Notably, the steady-state mRNA level of
      Spam1 in Rb(6.16) homozygotes was 25-30% of that in chromosomally normal consomic
      mice and those homozygous for Rb(2.8) (7.18). In Rb(6.16) and Rb(6.15)
      heterozygotes the levels were 61% and 66% of the normal. Studies are currently
      under way to determine the protein levels and gene structure of Spam1, to detect
      the underlying cause of the mRNA reduction associated with these translocations.

PMID- 9041128
TI  - Molecular cloning, structural analysis, and expression of carp ZP2 gene.
AB  - The cDNAs encoding carp ZP2 homologous to winter flounder and mammalian ZP2 were
      cloned. Carp ZP2 contains a tandemly repetitive domain and a nonrepetitive
      domain. A repeat is composed of 13 amino-acid residues whose consensus sequence
      is QQTSQQFQPQKPA/V. The length of the repetitive domain is highly variable, but
      that of the nonrepetitive domain is fairly constant among various cDNAs. The
      termination codons of various cDNAs appear at three different positions. Three
      groups of cDNAs were therefore categorized. Groups I-III encode a nonrepetitive
      domain of 356, 255, and 10 residues, respectively. A carp ZP2 gene corresponding
      to group II cDNA was cloned. It spans 2.4 kb and consists of eight exons and
      seven introns. Carp ZP2 mRNA was detected only in oocytes but not in other
      tissues. Carp ZP2 is heterogenous in size. The molecular weight ranges from 40-80
      kDa. It is present in vitellogenic but not in previtellogenic oocytes, nor in
      other tissues. Carp ZP2 content in oocytes increases as vitellogenesis proceeds.

PMID- 9041129
TI  - Regulation of gene expression in the preimplantation mouse embryo: temporal and
      spatial patterns of expression of the transcription factor Sp1.
AB  - Activation of the embryonic genome during preimplantation mouse development
      entails a dramatic reprogramming of the pattern of gene expression. The
      complement of transcription factors that are present in the early embryo and that
      must intrinsically be involved in this reprogramming is essentially
      uncharacterized. We and others have demonstrated that transcription factor Sp1 is
      present in the mouse oocyte and early cleavage stage preimplantation embryo. Due
      to Sp1's prominent role in regulating the expression of a vast array of genes
      that are involved in cell proliferation and differentiation, as well as in
      general housekeeping functions, we characterized the temporal and spatial
      patterns of Sp1 expression during preimplantation development. The relative
      abundance of Sp1 transcripts, as well as transcripts for the TATA box-binding
      protein TBP, decreases during oocyte maturation and reaches a minimum level in
      the two-cell stage, after which time the abundance of these transcripts increases
      progressively to the blastocyst stage. Immunoblotting experiments detect Sp1
      species of Mr = 95,000 and 105,000 at all stages of preimplantation development.
      The amount of Sp1 increases about 8-fold during preimplantation development, and
      an alpha-amanitin-insensitive increase is observed between G1 and G2 of the one
      cell embryo; this increase may reflect the mobilization of a maternal Sp1
      transcript. Immunocytochemical experiments also reveal a similar increase in the
      amount of Sp1 during preimplantation; the nuclear concentration of Sp1 is greater
      in the trophectoderm cells than in the inner cell mass cells. Finally, gel-shift
      experiments document an increase during preimplantation development of a DNA
      binding activity that is likely due to Sp1. These increases in the abundance of
      the Sp1 protein and an Sp1-like DNA-binding activity parallel increases in the
      rate of transcription that occur during preimplantation development.

PMID- 9041130
TI  - Effects of amino acids and alpha-amanitin on bovine embryo development in a
      simple protein-free medium.
AB  - Five experiments, utilizing 3741 embryos produced in vitro, were designed to test
      the effects of Eagle's nonessential amino acids, and combinations of Eagle's
      essential amino acids and the RNA polymerase inhibitor alpha-amanitin on the
      development of preimplantation bovine embryos in a modified protein-free KSOM
      medium. Embryos were cultured in 5% O2:5% CO2:90% N2 at 39 degrees C for the
      first 40-44 hr in modified KSOM, and embryos with > or = 4 cells were cultured in
      modified KSOM-PVA with different amino acids in experiments 1-4, and with the
      addition of alpha-amanitin in experiment 5. In experiment 1, addition of 0.5x of
      the essential amino acids, with different concentrations of nonessential amino
      acids significantly increased hatching of blastocysts and decreased blastocyst
      degeneration, but increasing the nonessential amino acids from 1x to 5x, did not
      stimulate embryo development. In experiments 2-4, increasing only the glycine
      concentration, or adding each of the 12 essential amino acids singly or several
      in combination to the medium containing nonessential amino acids, did not
      significantly improve embryo development. Taurine (0.4 mM) in the modified KSOM
      medium reduced blastocyst degeneration. In experiment 5, alpha-amanitin (20
      microM) completely inhibited further embryo development when it was added at
      several stages from 4-cell embryos to morulae. The study with protein-free KSOM
      plus amino acids provided a completely defined simple medium for culturing bovine
      embryos, with evidence that continuous mRNA activity and presumed protein
      synthesis was obligatory to meet the complex and continuous requirements for
      proteins by the developing blastocyst.

PMID- 9041131
TI  - Biochemical changes in the equine capsule following prostaglandin-induced
      pregnancy failure.
AB  - The equine embryonic capsule, an acellular covering that envelops the conceptus
      during the second and third weeks of pregnancy, is composed of mucin-like
      glycoproteins. Its structure is consistent with a dual role during early
      pregnancy: protection of the conceptus, and communication between the embryo and
      the mother. Loss of sialic acid from the capsular glycoproteins at day 16
      correlates with the time of "fixation," or loss of conceptus mobility throughout
      the uterine horns. This study investigated how the structure of the capsule is
      linked to the maintenance of pregnancy. Six pregnancies, confirmed by ultrasound,
      were terminated by prostaglandin injection on day 14, prior to the time of embryo
      fixation. These "defective" conceptuses were collected at day 17, and the
      structure and molecular properties of their capsules were compared to those of
      day 17 conceptuses collected from 5 normal pregnancies. Defective capsules were
      not significantly different from normal capsules in terms of dry weight, amino
      acid composition, and content of neutral and amino sugars. However, defective
      capsules failed to show the loss of sialic acid normally occurring around the
      time of embryo fixation. Analysis of the capsular mucins following trypsin
      digestion was carried out by radioactive labeling with 3H on sialyl
      oligosaccharides and 125I on tyrosine residues, followed by fast protein liquid
      chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis.
      Differences in the trypsin fragmentation patterns indicated increased
      susceptibility of the defective capsules to proteolysis. We conclude that there
      is a temporal association between desialylation of the equine capsule and
      embryonic survival, and that failure to desialylate alters the properties of the
      capsule.

PMID- 9041132
TI  - Cumulus cells of oocyte-cumulus complexes secrete a meiosis-activating substance
      when stimulated with FSH.
AB  - The effect of the different follicular cell types on resumption of meiosis was
      studied during stimulation with FSH. Cumulus enclosed oocytes (CEO), denuded
      oocytes (DO), and cumulus and mural granulosa cells were used. The resumption of
      meiosis and oocyte maturation were assessed by the determination of the germinal
      vesicle breakdown (GVBD) and polar body formation (PB) at the end of a 24 hr
      culture period in the presence of 4 mM hypoxanthine (HX). The effects of
      recombinant LH (r-LH) and hCG were also evaluated. Oocyte exposure to the
      gonadotrophins varied from 5 min to 24 hr (i.e., priming time). Oocytes were
      obtained from immature gonadotrophin-stimulated and -unstimulated mice. 1. FSH (1
      IU/L-75 IU/L) provoked a dose-dependent increase in GVBD and PB in CEO, but not
      in DO, in stimulated and unstimulated mice. Eight IU/L was sufficient for
      inducing resumption of meiosis. In contrast, LH and hCG (both 1 IU/L-1500 IU/L)
      were without effect on GVBD and PB in CEO and DO of oocytes from stimulated and
      unstimulated mice. A combination of 8 IU/L FSH and 4-8 IU/L hCG produced an
      additive effect, whereas combinations with LH and higher concentrations of hCG
      had no such effect. 2. A 2 hr priming with FSH (8 IU/L-75 IU/L) induced a dose
      dependent oocyte maturation in CEO. Thirty minutes of priming with FSH (75 IU/L)
      was sufficient for induction of meiotic resumption in CEO. 3. Priming CEO with
      FSH for 2 hr followed by the separation and repooling of oocytes and cumulus
      cells induced oocyte maturation. GVBD of new, unprimed DO added to cumulus cells
      of primed CEO increased slightly but was significant, whereas GVBD in DO isolated
      from the primed CEO only increased marginally. DO cocultured with FSH-primed
      cumulus masses seem to be prevented from resuming meiosis. 4. Priming a coculture
      of granulosa cells and DO with FSH for 2 hr caused a significant increase in GVBD
      compared to the control, evaluated after 24 hr. In contrast, a 24 hr FSH-priming
      of a coculture of granulosa cells and DO was without effect on GVBD. 5. A spent
      medium in which unstimulated cumulus cells or mural granulosa cells had grown was
      without effect on GVBD in DO. However, a small fraction of the DO resumed meiosis
      after culture in a spent medium derived from a 2 hr priming of CEO and spent
      media from 24 hr priming of CEO induced a 2-3 times higher GVBD frequency in the
      DO compared to the controls. Heat treatment of spent media (70 degrees C, 30 min)
      from a 24 hr FSH-priming of CEO still induced GVBD in naive DO. The results
      showed that FSH, in a concentration of as little as 8 IU/L, but not r-LH and hCG,
      induced within 30 minutes the cumulus cells to produce and after 2 hr to secrete
      a diffusible heat stable meiosis activating substance. This substance overcame,
      in a paracrine fashion, the inhibiting effect of HX and induced oocyte maturation
      directly in DO. The production of this substance, however, was dependent on the
      initial connection between the cumulus cells and the oocyte, indicating an
      important 2-way communication between these 2 cell types. The mural granulosa
      cells did not produce a meiosis inducing activity by stimulation with FSH, but
      significantly, more DO matured after coculture with the nonstimulated granulosa
      cells for 24 hr than for 2 hr. It is proposed that the heat stable meiosis
      activating component of the spent media from the FSH-stimulated CEO belongs to
      the meiosis activating sterols, MAS, previously isolated from human follicular
      fluid and from adult bull testes.

PMID- 9041133
TI  - Fate of hamster oviductin in the oviduct and uterus during early gestation.
AB  - Oviductins are a family of glycoproteins which are synthesized and secreted by
      oviductal secretory cells and which, upon their secretion in the lumen of the
      oviduct, become associated with postovulatory oocytes and developing embryos.
      Recently, we showed that hamster oviductin is maximally secreted in the oviduct
      at the time of ovulation and is later associated with a certain population of
      uterine epithelial cells, where it is subsequently endocytosed and degraded. In
      light of these results, this study was conducted to follow the fate of hamster
      oviductin in the oviduct and uterus during early gestation. Using a monoclonal
      antibody against hamster oviductin, immunofluorescence and immunogold labeling
      revealed that during early gestation, immunoreactivity to oviductin in the uterus
      gradually diminished to an almost total disappearance at time of implantation.
      However, the strong labeling intensity remained unchanged in the oviduct.
      Biochemical analyses demonstrated that a degradation of oviductin occurs in the
      uterus, and a loss of immunoreactivity was also observed as gestation progressed,
      so that by the time of implantation, immunoreactivity to oviductin was barely
      detectable. The decrease of oviductin along the uterine epithelium at the time of
      blastocyst attachment and its final disappearance at implantation suggest that
      this glycoprotein could be a potential modulator of uterine receptivity.

PMID- 9041134
TI  - Capacitation-like changes occur in mouse spermatozoa cooled to low temperatures.
AB  - Previously we showed that >70% of mouse spermatozoa cooled slowly from 37 degrees
      C to 4 degrees C and warmed have undergone capacitation-like changes as examined
      by a chlortetracycline staining assay. These membrane changes are reflected in
      the ability of cooled spermatozoa to achieve fertilization rates in vitro similar
      to those of uncooled controls when added to oocytes immediately upon warming. The
      aim of this study was to determine the nature of these membrane changes. We found
      they were not dependent upon the rate of cooling to 4 degrees C and similar
      changes were observed when spermatozoa were cooled to higher temperatures (10
      degrees and 20 degrees C), but it took longer for 50% of the spermatozoa to
      undergo such changes (3, 18, and 27 min for spermatozoa held at 4 degrees, 10
      degrees, and 20 degrees C, respectively). Mixing cooled spermatozoa with oocytes
      immediately upon warming produced fertilization rates similar to fresh
      spermatozoa capacitated in vitro for 90 min before the oocytes were added. The
      rate of sperm penetration as determined by the fluorescent DNA stain Hoescht
      33258 was also similar. However, the penetration time for cooled spermatozoa was
      significantly shortened when they were preincubated for 90 min before being added
      to oocytes. We conclude that membrane changes resembling capacitation (1) occur
      during cooling to temperatures above freezing, (2) are independent of cooling
      rate, (3) proceed faster at lower temperatures, and (4) obviate the need for
      prior capacitation in vitro before mixing with oocytes.

PMID- 9041135
TI  - In vivo aging of oocytes influences the behavior of nuclei transferred to
      enucleated rabbit oocytes.
AB  - The present study examined nuclear remodeling in rabbit nuclear transfer (NT)
      embryos formed from metaphase II (MII) oocytes aged in vivo until 19 hr
      postcoitum (hpc), enucleated, and fused at 22-26 hpc with 32-cell morula
      blastomeres by means of electric fields, which also induced recipient oocyte
      activation. Post-activation events observed during the first hour following the
      fusion/activation pulse were studied in terms of chromatin, lamins, and
      microtubules, and revealed that transferred nuclei underwent premature
      chromosomes condensation (PCC) in only one-third of NT embryos and remained in
      interphase in others. Recipient oocytes were mostly not activated by
      manipulations performed before the fusion/activation pulse. The persistence of
      transferred nuclei in interphase resulted from the rapid progression of recipient
      oocytes to interphase after activation, suggesting that the cytoplasmic state of
      MII oocytes aged in vivo was poised for the approach to interphase. Studying
      microtubular organization in MII oocytes before nuclear transfer manipulations,
      we found that 19 hpc MII oocytes aged in vivo differed from 14 hpc MII oocytes
      (freshly ovulated) and from 19-hpc MII oocytes aged in vitro (collected at 14 hpc
      and cultured for 5 hr), notably by the presence of microtubule asters and tubulin
      foci or only tubulin foci dispersed throughout the cytoplasm. When PCC was
      avoided, remodeling of the transferred nucleus was well advanced 1 hr after
      nuclear transfer, and NT embryos developed better to the blastocyst stage.

PMID- 9041136
TI  - Isolation and characterization of a rabbit epididymal secretory glycoprotein that
      associates to the spermatozoon surface.
AB  - Using a combination of gel filtration and hydroxyapatite chromatography, a major
      secretory glycoprotein (EP140) was purified from rabbit epididymal fluid. The
      protein had an apparent Mr of approximately 140 kDa under native conditions but
      dissociated into 2 equimolar amounts of glycosylated subunits, alpha and beta of
      Mr 35 and 33 kDa, upon sodium dodecylsulfate polyacrylamide gel electrophoresis
      in absence of reducing agents. Thus EP140 appears to be a tetramer composed of 2
      alpha and 2 beta subunits, held together by noncovalent forces. Proteolytic
      peptide mapping, amino acid analysis, and determination of partial amino acid
      sequences suggested that the 2 subunits were very similar, differing only at some
      punctual residues in their primary structures. The amino acid sequences obtained
      did not show significant similarity to any known protein. Western blot
      determinations with a specific antibody indicated that no EP140-immunorelated
      protein was detected either in testis or blood from the rabbit nor in
      epididymides from rats or hamsters. EP140 was shown to associated to the
      spermatozoon surface, mainly at the acrosomal zone and in the middle piece, and
      this association progressively increased during the transit of the spermatozoon
      through the epididymis.

PMID- 9041137
TI  - Identification of bovine zona pellucida glycoproteins.
AB  - Despite the economical importance of in vitro gamete technologies in cattle, only
      little is known about the molecular mechanisms of binding of spermatozoa to the
      zona pellucida (ZP) of the oocyte. The aim of the present work was to identify
      proteins from the bovine zona pellucida (bZP) and to investigate which bZP
      proteins play a role in sperm-egg binding. High resolution 2-dimensional
      polyacrylamide gel electrophoresis of bZP proteins under reducing conditions
      showed that the bovine ZP could be separated into 4 glycoprotein spots,
      provisionally named bZP1, bZP2, bZP3, and bZP4, with different molecular masses
      and isoelectrical points. The N-terminal amino acid sequence of bZP1, bZP2, and
      bZP4 could be determined. The N-terminal amino acid sequences of bZP1 and bZP4
      were identical and were homologous to that of pZP4. Comparison of our data to
      that of Noguchi et al., 1994 (Biochim Biophys Acta 1201:7-14) revealed that bZP2
      and bZP4 are fragments of bZP1. Immunoblot analysis showed that, respectively,
      anti-porcine-ZP3alpha and -ZP3beta antibodies recognized 2 distinct regions of
      the bZP3 spot. Both antibodies inhibited sperm-egg binding in the bovine. We
      conclude that the bovine ZP consists of 3 proteins that correspond by size, N
      terminal amino acid sequence, and antigenic determinants of pZP1, pZP3alpha, and
      pZP3beta, respectively, that are encoded by the porcine ZPA, ZPB, and ZPC genes
      (Harris et al., 1994: J Seq Map 4:6331-393), respectively.

PMID- 9041138
TI  - Stage specific effects of carbendazim (MBC) on meiotic cell cycle progression in
      mouse oocytes.
AB  - The effects of the pesticide carbendazim (MBC) on the in vitro meiotic maturation
      of mouse oocytes were evaluated using conventional and confocal fluorescence
      microscopy. The response of oocytes exposed to 0, 3, 10, or 30 microM MBC during
      meiotic maturation was analyzed with respect to chromosome organization, meiotic
      spindle microtubules, and cortical actin using fluorescent labels for each of
      these structures. Continuous exposure to MBC during the resumption of meiosis
      resulted in a dose-dependent inhibition of meiotic cell cycle progression at
      metaphase of meiosis-1. Drug exposure at the metaphase-anaphase transition of
      meiosis-1 did not interfere with cell cycle progression to metaphase-2 except at
      high concentrations (30 microM). At the level of spindle microtubule
      organization, MBC caused a loss of nonacetylated microtubules and a decrease in
      spindle size at 3 or 10 microM concentrations. Thirty microM MBC prevented
      spindle assembly when added at the beginning of meiotic maturation or caused
      spindle pole disruption and fragmentation when added to preformed spindles.
      Spindle disruption involved a loss of phosphoprotein epitopes, as monitored by
      MPM-2 staining, and resulted in the appearance of dispersed chromosomes that
      retained a metaphase-plate location on spindle fragments associated with the
      oocyte cortex. Polar body extrusion was impaired by MBC, and abnormal polar
      bodies were observed in most treated oocytes. The results suggest that MBC
      disrupts cell cycle progression in mouse oocytes by altering meiotic spindle
      microtubule stability and spindle pole integrity.

PMID- 9041139
TI  - Human fertilin beta: identification, characterization, and chromosomal mapping of
      an ADAM gene family member.
AB  - Fertilin alpha/beta (PH30 alpha/beta) is a heterodimeric sperm surface protein
      containing binding and fusion domains with potential for interaction with
      integrin receptors on the oocyte. We report the cDNA cloning, deduced amino acid
      sequence, tissue specificity, and chromosomal mapping of human fertilin beta.
      Encoded by a 2205 nucleotide open reading frame, the deduced amino acid sequence
      of human fertilin beta contains pro-, metalloprotease-like, disintegrin-like,
      cysteine-rich, epidermal growth factor-like (EGF) repeat, transmembrane, and
      cytoplasmic domains. Due to this domain organization, human fertilin beta has
      been identified as a member of the ADAM family, which is composed of membrane
      anchored proteins having A Disintegrin And Metalloprotease domain. The amino acid
      sequence of human fertilin beta shares 90%, 56%, and 55% identity, respectively,
      to monkey, guinea pig, and mouse fertilin beta homologs. A phenylalanine
      glutamate-glutamate (FEE) binding tripeptide within the disintegrin-like domain
      of human fertilin beta, homologous to other fertilin beta RGD-like (arginine
      glycine-aspartic acid) tripeptides, could compete for recognition by integrins
      and other receptors. Northern analysis from 16 human tissues revealed human
      fertilin beta's 2.9 kb message only in testis, which raises interest in possible
      clinical applications of this molecule as a contraceptive vaccinogen. Human
      fertilin beta maps to chromosome 8, band p11.2, by fluorescence in situ
      hybridization and mouse/human somatic cell hybrid Southern hybridization.

PMID- 9041140
TI  - Spermatozoa lacking acrosin protein show delayed fertilization.
AB  - Acrosin (ACR), a serine proteinase located in the acrosome of the sperm, has been
      presumed to be involved in the recognition and binding of the sperm to the zona
      pellucida of the ovum and the sperm penetration through the zona pellucida. To
      examine the function of acrosin in vivo, we have generated mice carrying a
      mutation at the acrosin locus (Acr) through targeted disruption in embryonic stem
      (ES) cells. One chimeric male and female transmitted the targeted gene through
      their germ line. Homozygous Acr-/- mice are fertile and yield litters comparable
      in number and size to those of Acr+/+ mice. These data show that sperm of the
      homozygous Acr-/- mice are able to penetrate the zona pellucida, fertilize the
      ovum, and produce viable offspring. However, spermatozoa lacking acrosin protein
      show a delayed fertilization. One chimeric male which contained the targeted gene
      in 20% of its sperm transmitted only the Acr+ allele to its progeny. Furthermore,
      in vitro fertilization with equally mixed sperm cells of Acr+/+ and Acr-/- mice
      resulted in fertilization only with the Acr+ sperm cells. Incubation of oocytes
      with Acr+ or Acr- sperm show that the Acr+ sperm are faster to fertilize the
      oocytes than the Acr- sperm cells. These results suggest that Acr- sperm have a
      selective disadvantage when they are in competition with Acr+ sperm.

PMID- 9041141
TI  - The 26 kD protein recognized on rat cauda epididymal sperm by monoclonal antibody
      4E9 has internal peptide sequence that is identical to the secreted form of
      epididymal protein E.
AB  - MAb 4E9, raised against a detergent extract of rat cauda epididymal sperm,
      recognizes a 26 kD glycoprotein that is found on the plasma membrane of the sperm
      tail in cauda, but not caput, sperm (Moore et al., 1994). It also recognizes an
      epididymis-secreted protein that has been shown to be protein E (Xu and Hamilton,
      1996). It is felt that the secreted protein becomes associated with sperm, but
      there has been no biochemical evidence of molecular identity between the secreted
      and membrane proteins. In this report, the membrane form of the antigen has been
      purified by reverse phase HPLC. Cyanogen bromide cleavage of the purified protein
      yielded 3 peptides that were purified, also by reverse phase HPLC. One of the
      peptides yielded an unambiguous sequence of 34 amino acids that is identical to
      an internal peptide of the protein found in epididymal fluid. This is the first
      report showing sequence identity between an epididymis-secreted protein and a
      protein of the sperm plasma membrane.

PMID- 9041142
TI  - Ribosomal S6 kinase p90rsk and mRNA cap-binding protein eIF4E phosphorylations
      correlate with MAP kinase activation during meiotic reinitiation of mouse
      oocytes.
AB  - During meiotic reinitiation of the mouse oocyte, entry into M-phase is regulated
      by changes of protein phosphorylation and by the stimulation of selective mRNA
      translation following the nuclear membrane dissolution. Our results reveal that M
      phase kinases (MAP kinase and histone H1 kinase) are being activated together
      with S6 kinase and with the phosphorylation of eIF4E, the cap-binding subunit of
      the initiation factor eIF-4F. In order to test which signaling pathway(s) is(are)
      involved, okadaic acid and cycloheximide have been used as tools for
      differentially modulating MAP and histone H1 kinase activities. A role for MAP
      kinases in the phosphorylation of eIF4E and the activation of S6 kinase is
      suggested. The possible implication of p90rsk and/or of p70s6k in the overall
      increase in S6 kinase activity has been examined. p70s6k does not appear to be
      involved since phosphorylated forms are found in prophase and maturing oocytes.
      In contrast, p90rsk is phosphorylated and activated in maturing oocytes. p90rSk
      phosphorylation correlates with the activation of S6 kinase. These results
      suggest that the overall increase of S6 kinase activity is mostly due to p90rsk
      activation. The roles of eIF4E phosphorylation and S6 kinase activation in the
      physiological induction of M-phase and in the okadaic acid-induced premature
      mitotic events are discussed.

PMID- 9041143
TI  - Hyaluronidase activity of macaque sperm assessed by an in vitro cumulus
      penetration assay.
AB  - A model system consisting of cynomolgus macaque sperm and ovulated hamster ova
      cumulus complexes (OCCs) was utilized to study the role of the sperm protein PH
      20 in cumulus penetration. The hyaluronidase activity of solubilized macaque
      sperm PH-20 was evaluated using an ELISA-like microplate assay prior to and
      following the addition of the hyaluronidase inhibitors heparin (0-100 microg/ml)
      and apigenin (250 microM), as well as the Ig fraction of a polyclonal antibody
      raised against purified recombinant macaque PH-20 (R10; 10-400 microg/ml). Sperm
      motility following exposure to enzyme inhibitors was evaluated using computer
      aided sperm motility analysis. Macaque sperm were labeled with the permeant
      fluorescent nuclear dye, Hoechst 33342, and were coincubated with ovulated
      hamster OCCs for 30 min at 37 degrees C. The addition of heparin, apigenin, or
      R10 antibody to solubilized sperm extracts resulted in a linear dose-dependent
      decrease in hyaluronidase activity (P < .01). In the heterologous cumulus
      penetration assay, fluorescently labeled macaque sperm that were pretreated with
      heparin (1-100 microg/ml), apigenin (250 microM), or R10 antibody (Ig fraction,
      10-400 microg/ml) demonstrated a dose-dependent decrease in the ability to
      penetrate hamster OCCs (P < 0.01), in the absence of effects on sperm motility.
      In the homologous assay, experiments using macaque OCCs and fluorescently labeled
      macaque sperm confirmed that the same concentrations of heparin and R10 antibody
      similarly suppressed spermatozoal cumulus penetration (P < .01). These results
      suggest that macaque sperm PH-20-derived hyaluronidase participates in cumulus
      penetration in this species, and that this model system is useful for further
      studies into primate gamete interaction.

PMID- 9041144
TI  - Effects of epidermal growth factor and follicle-stimulating hormone during in
      vitro maturation on cytoplasmic maturation of porcine oocytes.
AB  - The present study was undertaken to investigate the influence of epidermal growth
      factor (EGF) and follicle-stimulating hormone (FSH) during in vitro maturation on
      cytoplasmic maturation of porcine oocytes as revealed by the success of
      fertilization and by the changes in the pattern of protein synthesis in oocytes
      and cumulus cells. For fertilization studies, oocyte-cumulus cell complexes (OCC)
      were cultured in media containing human recombinant EGF (1 ng/ml) or FSH (1.5
      microg/ml) or both for 44 hr prior to fertilization with fresh sperm for 6-8 hr.
      The oocytes were then fixed, stained, and examined as whole mounts following an
      additional 14 hr of culture. Addition of EGF, FSH, and EGF + FSH significantly
      increased the proportion of oocytes reaching MII stage. The addition of EGF alone
      significantly decreased the percentage of polyspermic oocytes and increased the
      proportion of monospermic oocytes forming 2 normal pronuclei. FSH abolished these
      effects of EGF and significantly increased the percentage of polyspermic oocytes
      forming more than 2 pronuclei when added alone or with EGF. For protein analysis,
      OCC were cultured in media containing the above hormones for 6, 24, and 44 hr and
      exposed to 0.5 mCi/ml L-[35S]methionine during the last 3 hr of cultures. The
      oocytes and cumulus cells were separated prior to lysis in SDS sample buffer, and
      denatured polypeptides were separated by 1-dimensional SDS-PAGE. In the oocyte,
      addition of EGF and FSH alone stimulated the synthesis of 34, 45, and 97 kDa
      proteins after 6 hr of culture; however, the addition of EGF and FSH together was
      without any effect. After 24 hr, EGF alone inhibited the synthesis of these
      peptides, whereas FSH alone and with EGF maintained the stimulation of synthesis
      of 34 and 45 kDa proteins. Two additional peptides corresponding to 66 and 200
      kDa appeared at this time as a result of exposure to FSH alone or with EGF. After
      44 hr of culture, these 2 new peptides were observed in all groups and the
      stimulatory effect of FSH and FSH + EGF was still evident. An additional peptide
      of 26 kDa appeared at this time as a result of FSH and EGF + FSH treatments. In
      the cumulus cells, EGF and FSH each alone induced the synthesis of a new peptide
      of 26 kDa after 6 hr of culture. FSH when added alone or with EGF induced the
      synthesis of an additional peptide of 29 kDa, the synthesis of which remained
      unchanged at 24 and 44 hr. After 24 hr, FSH alone and in combination with EGF
      induced the synthesis of an additional 38 kDa peptide and its synthesis was still
      maintained at 44 hr. EGF alone had no effect on protein synthesis in cumulus
      cells at 24 and 44 hr. These studies indicate that EGF may have a physiological
      role in the regulation of cytoplasmic maturation of porcine oocytes.

PMID- 9041145
TI  - Chlortetracycline analysis of boar spermatozoa after incubation, flow cytometric
      sorting, cooling, or cryopreservation.
AB  - In this study, the effects of staining procedure with chlortetracycline (CTC) and
      method of analysis of boar spermatozoa after staining were examined. The
      hypothesis that incubation, flow cytometric sorting, cooling, and
      cryopreservation cause changes to boar sperm membranes which resemble
      capacitation and the acrosome reaction was also tested. Membrane status was
      evaluated by flow cytometry and by fluorescence microscopy after staining with
      CTC, and acrosome integrity was checked by flow cytometry after staining with
      FITC-pisum sativum agglutenin and propidium iodide (PI). Flow cytometry was also
      used to assess viability (percentages of live and dead cells) of boar sperm after
      staining with SYBR-14 and PI. Staining of spermatozoa with CTC alone and in
      combination with PI and/or Hoechst 33342 had no effect on the proportion of
      spermatozoa allocated to the F (uncapacitated), B (capacitated), or AR (acrosome
      reacted) CTC fluorescent staining categories. The mean percentages of acrosome
      intact and acrosome-reacted cells were 88.4 and 6.8 or 0.8 and 96.5 in semen
      treated with 0 or 100 microg/ml lysophosphatidylchloine (LPC), respectively (P <
      0.001). Most spermatozoa were also in the AR CTC-stained category after treatment
      with LPC compared with a small proportion in the controls. Using flow cytometry
      to examine sperm suspensions stained with CTC, a gated population of spermatozoa
      with low fluorescence (population 1) comprised predominantly F-pattern cells (F
      pattern: population 1 vs. population 2, 80.5 vs. 14.4%; P < 0.001), whereas
      population 2 (high fluorescence) comprised mainly B-pattern cells (B-pattern:
      population 1 vs. population 2, 8.5 vs. 62.3%; P < 0.001). Incubation (38 degrees
      C, 4 hr), flow sorting, cooling (to 15 or 5 degrees C) and freezing reduced the
      proportion of F-pattern and live spermatozoa, and increased the proportion of B-,
      AR-pattern, and dead spermatozoa, in comparison with fresh semen. There were more
      membrane changes in spermatozoa cooled to 5 degrees C (30.4, 48.5, 21.1%) than in
      those cooled to 15 degrees C (56.1, 32.6, 11.5% F-, B-, and AR-pattern
      spermatozoa, respectively).

PMID- 9041146
TI  - H19 in normal development and neoplasia.

PMID- 9041147
TI  - Retropharyngeal lymphadenopathy in patients with nasopharyngeal carcinoma: a
      computed tomography-based study.
AB  - BACKGROUND: The purpose of this study was to investigate the incidence and
      prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma
      patients using contrast enhanced computed tomography (CT). METHODS: From January
      1989 to December 1991, 364 patients with newly diagnosed nasopharyngeal carcinoma
      without distant metastasis had a baseline CT performed. All patients had
      radiotherapy as their primary treatment. Eighty-seven patients also received
      neoadjuvant chemotherapy for locally advanced disease. All patients with clinical
      N0 disease had prophylactic lymph node irradiation. The contrast enhanced CT
      given prior to all treatment was evaluated for the presence of retropharyngeal
      lymphadenopathy. Criteria for involved lymph nodes included a lymph node size of
      10 mm or more, the presence of central necrosis within the lymph node, or the
      presence of a contrast enhancing rim. RESULTS: The incidence of retropharyngeal
      lymphadenopathy was 29.1%. A higher incidence of retropharyngeal lymph node
      involvement was observed in Ho's T2/T3 disease compared with T1 disease, and a
      higher incidence was also found in patients with cervical lymph node disease
      compared with those with clinical N0 disease. No significant differences in
      relapse free survival rates, local control rates, lymph node control rates, or
      distant failure rates were observed between patients with or without
      retropharyngeal lymphadenopathy after adjusting for T and N classifications. In
      134 patients with clinical N0 disease, retropharyngeal lymphadenopathy was found
      in 21 patients, whereas 113 had no evidence of retropharyngeal lymphadenopathy.
      However, no significant difference in treatment outcome was observed between the
      two groups. CONCLUSIONS: Using CT imaging, the presence of retropharyngeal
      lymphadenopathy in patients with nasopharyngeal carcinoma does not appear to
      affect the prognosis. In patients with clinical N0 disease, the identification of
      retropharyngeal lymphadenopathy based only on CT imaging is not sufficient
      evidence for an N1 classification.

PMID- 9041148
TI  - High level of urokinase-type plasminogen activator is a new prognostic marker in
      patients with gastric carcinoma.
AB  - BACKGROUND: Prognosis of gastric carcinoma is related to invasion and metastasis.
      Evidence has accumulated that invasion and metastasis in solid tumors require the
      action of tumor-associated proteases, which promote the dissolution of the
      surrounding tumor matrix and the basement membrane. The serine protease urokinase
      type plasminogen activator (uPA) and its inhibitor, plasminogen activator
      inhibitor-1 (PAI-1), appear to have a major function in these processes. Recent
      reports have demonstrated that expression of these proteolytic enzymes is
      elevated in breast and colon carcinoma and that it can be associated with
      invasiveness and poor prognosis. Therefore, the authors evaluated whether the
      expression and activation of uPA and PAI-1 might be of clinical value as a
      tumor/biologically defined risk factor in patients with gastric carcinoma.
      METHODS: Enzyme-linked immunoadsorbent assays were used to test for uPA antigens
      and PAI-1 in tissue extracts of normal and cancerous tissue from 160 gastric
      carcinoma patients who were enrolled in the Yonsei Cancer Center Study Group.
      RESULTS: Both uPA and PAI-1 levels were significantly higher in cancerous tissues
      than in normal tissues (uPA: 9.4 +/- 8.7 vs. 5.3 +/- 3.1 ng/mg protein cytosol;
      PAI-1: 10.9 +/- 9.1 vs. 5.8 +/- 2.9 ng/mg protein cytosol), (P < 0.001,
      respectively). Both high uPA and PAI-1 levels were associated with
      differentiation of the tumor (P = 0.04 and P = 0.004, respectively), and a high
      PAI-1 level was associated with lymph node metastasis at an advanced stage (P =
      0.003 and P = 0.04, respectively). There was a correlation between the levels of
      uPA and PAI-1 expression in cancerous tissues (correlation coefficient = 0.57).
      In univariate analysis, a high level of uPA or PAI-1 was associated with a short
      relapse free survival, but in multivariate analysis only a high level of uPA was
      an independent prognostic parameter for a short relapse free survival for gastric
      carcinoma patients. CONCLUSIONS: These data indicate that uPA is a new
      independent variable for the identification of high risk gastric carcinoma
      patients. Therefore, therapy targeting uPA can be applied as a new biologic
      treatment modality for these individuals.

PMID- 9041149
TI  - Improved mortality rate of gastric carcinoma patients with peritoneal
      carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined
      with surgery.
AB  - BACKGROUND: Peritoneal carcinomatosis from gastric carcinoma has a very poor
      prognosis. The purpose of this study was to evaluate the efficacy of
      intraperitoneal hyperthermic chemoperfusion (IHCP) in advanced gastric carcinoma
      patients with peritoneal carcinomatosis. METHODS: IHCP combined with aggressive
      surgery was performed in 48 gastric carcinoma patients with peritoneal
      carcinomatosis; 18 gastric carcinoma patients with peritoneal carcinomatosis
      serving as controls were treated with surgery alone. RESULTS: The survival period
      was extended for the 48 patients who underwent surgery plus IHCP compared with
      the control patients (P = 0.00167). Of the 29 patients with peritoneal
      carcinomatosis in the upper abdominal cavity, the 21 patients treated with IHCP
      and surgery had survival periods superior to those of the 8 patients treated by
      surgery alone (P = 0.000817). The 5-year survival rate of the 18 IHCP patients
      with countable metastases in the entire cavity was 41.6%, whereas the 50%
      survival duration of the control group was 110 days. Nineteen patients with
      numerous metastases in the entire cavity died within 673 days, regardless of
      whether or not IHCP was used. CONCLUSIONS: Peritoneal carcinomatosis is not a
      disease beyond treatment. IHCP treatment combined with extensive surgery provides
      an effective and practical method of treating this disease entity.

PMID- 9041150
TI  - The role of lymph node dissection in the treatment of gallbladder carcinoma.
AB  - BACKGROUND: Lymph node involvement is an important prognostic factor in
      gallbladder carcinoma (GBC). The lymph node involvement pattern, extent, and
      indications for systematic lymph node dissection for patients with advanced GBC
      were investigated. METHODS: Forty-one patients with GBC who underwent radical
      resection with systematic regional lymph node dissection over the past 11 years
      were analyzed. RESULTS: The lymph node metastasis rate was 63.4% overall, 0% in
      pT1 disease, 61.9% in pT2 disease, and 81.3% in pT3/pT4 disease. When reviewed
      according to site, the rate was 41.5% in pericholedochal lymph nodes, 22.0% in
      the lymph nodes around the common hepatic artery and the portal vein, 36.6% in
      the posterior pancreaticoduodenal lymph nodes, 28% (5/18) in the celiac lymph
      nodes, 19% (3/ 16) in the superior mesenteric artery (SMA) lymph nodes, and 26%
      (7/27) in the aortocaval paraaortic lymph nodes. Patients with severe
      hepatoduodenal ligament invasion had high rates of paraaortic lymph node
      involvement. The mortality rate was 2.4% (1 of 41 patients) and the 5-year
      survival rate was 33.1% overall, 100% in patients with pT1 disease, 49.8% in
      patients with pT2 disease, and 0% in patients with pT3/pT4 disease. The 5-year
      survival rate for pT2 disease according to lymph node involvement was 72.7% in
      patients with pN0+ pN1+ positive posterior pancreaticoduodenal lymph nodes and
      positive lymph nodes around the common hepatic artery in the N2 patients and 0%
      in the patients with positive celiac and SMA lymph nodes in the N2 patient group
      or the positive paraaortic lymph node group (P < 0.05). CONCLUSIONS: These
      results suggest that systemic dissection of N1 lymph nodes, posterior
      pancreaticoduodenal lymph nodes, and lymph nodes around the common hepatic artery
      and the portal vein in N2 patients is necessary to improve the prognosis of those
      patients with pT2 disease without moderate or severe hepatoduodenal ligament
      invasion.

PMID- 9041151
TI  - Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients
      with intraductal papillary mucinous tumors of the pancreas.
AB  - BACKGROUND: The authors previously found specific mutations of the K-ras gene at
      codon 12 in the pancreatic juice of 67% of patients (6 of 9) with pancreatic
      ductal carcinoma, and the detection of these mutations was useful for diagnosis.
      This study was performed to detect and evaluate K-ras mutations in pancreatic
      juice from patients with intraductal papillary mucinous tumor of the pancreas,
      which is considered a low grade malignancy. The results were interpreted from the
      viewpoint of clinical significance. METHODS: K-ras mutations were examined using
      seminested polymerase chain reaction analysis combined with restriction enzyme
      digestion, followed by nonradioisotopic single strand DNA conformation
      polymorphism. RESULTS: Twelve of thirteen cases (92%) of intraductal papillary
      mucinous tumor of the pancreas, confirmed histologically (9 adenomas and 4
      carcinomas), and 26 of 43 cases (60%) of ductal carcinoma showed specific K-ras
      gene mutations in the pancreatic juice. Furthermore, 4 of 22 patients (18%) with
      chronic pancreatitis, followed for more than 1 year without a sign of pancreatic
      tumor, showed K-ras mutations. In contrast, no mutations of the K-ras gene were
      detected in the pancreatic juice from 28 normal controls. CONCLUSIONS: K-ras
      mutations were found in the pancreatic juice of all but one patient with
      intraductal papillary mucinous tumor of the pancreas, but they were not useful
      for distinguishing carcinoma from adenoma. The authors concluded that K-ras
      mutations are not a specific marker for pancreatic neoplasms because similar
      mutations were detected in the pancreatic juice from patients with chronic
      pancreatitis. At the present time, the detection of K-ras mutations in pancreatic
      juice should be used clinically as an adjunct diagnostic modality for pancreatic
      diseases.

PMID- 9041152
TI  - Lung carcinoma trends by histologic type in Vaud and Neuchatel, Switzerland, 1974
      1994.
AB  - BACKGROUND: Shifts in the distribution of histologic types have reportedly
      accompanied changes in lung carcinoma incidence in the last two decades. In the
      United States, incidence rates of squamous cell and small cell carcinoma have
      been showing a decline in males, after peaks in 1981-82 and 1986-87,
      respectively; however, no decline has been observed in females. In both genders,
      adenocarcinoma incidence is increasing. The authors evaluated lung carcinoma
      incidence rates in two Swiss cantons for changes in trends by gender, birth
      cohort, and histologic type. METHODS: The authors analyzed data on population
      based lung carcinoma incidence from the Swiss cantons of Vaud and Neuchatel (the
      populations of which total about 760,000). Cancers were grouped into four major
      histologic types. The proportion of cancers not histologically confirmed was
      approximately 8% across the entire study period. Incidence rates were age
      standardized on the basis of the world standard population. RESULTS: Overall, of
      7423 cancer cases diagnosed in the period 1974-1994, squamous cell carcinomas
      accounted for 37%, small cell carcinomas and adenocarcinomas 18% each, and other
      carcinomas 16%. Rates of squamous cell and small cell carcinoma incidence in
      males of all ages dropped in the last quinquennium, while corresponding rates in
      females increased steadily. Conversely, adenocarcinoma incidence increased in
      both genders by approximately 2.5-fold; and during the period 1990-1994, in young
      adults of both genders, it was more than 3-fold higher than the incidence of
      squamous cell carcinoma. At variance with squamous cell carcinoma, the incidence
      of which reached its peaks in the 1910-20 birth cohorts in males and in the 1930
      40 birth cohorts in females, adenocarcinoma revealed a similar birth cohort
      pattern in the two genders, with still no sign of decline. CONCLUSIONS: Although
      changes in diagnostic practices may have played a role, the incidence data
      presented in this study suggest that adenocarcinoma is sustaining a new lung
      carcinoma epidemic, chiefly attributable to the switch to low-tar, filtered
      cigarettes. Its pattern seems remarkably similar in the two genders. Thus, the
      authors conclude that similar exposure to tobacco-related carcinogens leads to
      similar rates of histologic type-specific lung carcinoma incidence in males and
      females.

PMID- 9041153
TI  - Desmoplastic squamous cell carcinoma of skin and vermilion surface: a highly
      malignant subtype of skin cancer.
AB  - BACKGROUND: The prognosis of squamous cell carcinoma (SCC) of the skin is
      directly related to the development of metastases or local recurrence. This is
      affected by numerous factors, most of which are independent: clinical tumor size,
      histopathologic tumor thickness, depth of penetration, degree of cell
      differentiation, degree of keratinization, location, and immunosuppression. The
      determination of whether desmoplasia, previously described in only one case of
      SCC, constitutes an additional prognostic factor was the objective of this study.
      METHODS: The study was performed prospectively on 594 SCCs from 509 patients. All
      of the factors mentioned earlier were present. Forty-four SCCs were identified by
      light microscopy as desmoplastic due to their prominent trabecular growth
      patterns, narrow columns of atypical epithelial cells, and marked desmoplastic
      stromal reaction, in some cases with perineural and perivascular invasion. Follow
      up ranged from 4 to 10 years (median, 5.3 years). RESULTS: All tumors in the
      study patient population were treated using the paraffin section method of
      micrographic surgery. The 44 desmoplastic SCCs were found to metastasize 6 times
      more often than the remaining 550 tumors (22.7% vs. 3.8%), with 10 times as many
      local recurrences (27.3% vs. 2.6%). CONCLUSIONS: Desmoplasia is a highly
      significant (P < 0.001) prognostic factor for SCCs and is associated with the
      development of metastases or recurrence.